T Y P E 2 D I A B E T E S M E L L I T U S
Authors: Johan Wens, Patricia Sunaert, Frank Nobels, Luc Feyen,
Paul Van Crombrugge, Hilde Bastiaens, Paul Van Royen
Nederlandse
versie
Contents
Introduction
Problem description and substantiation of the guidelines
Definitions
Epidemiology
Issues at stake
Early detection
Early detection of Type 2 diabetes
Early detection of gestational diabetes
After the pregnancy
Diagnosis of diabetes mellitus
Diagnostic criteria
Difference between Type 1 and Type 2 diabetes
Treatment objectives
Diet and exercise advice
Prevention of Type 2 diabetes
Treatment approaches to Type 2 diabetes
Pharmacotherapy for Type 2 diabetes
Oral antidiabetics (OAD)
Insulin
Instructions for the correct use of insulin
Administration using an insulin pen
Monitoring risk factors to prevent cardiovascular complications
Managing cardiovascular risk
Early detection of cardiovascular disease
Acute and chronic complications
Acute complications
Chronic complications
Diabetes education
Self-monitoring
Glucose Self-Monitoring
Self-monitoring techniques
Availability of self-monitoring supplies
Organising the clinical follow-up
The Diabetes Passport
Agreeing on treatment objectives
Treatment compliance
Approach to Type 2 diabetes patient care
The diabetes team in second-line care
The diabetes team in first-line care
Communication between care providers
Patient associations
Conclusion and recommendations
Fundamentals
Research agenda
Implementation
Levels of evidence
Definitions
Patient involvement and evaluation by the general practitioner
These recommendations for good medical practice are an indicative set of guidelines in support of diagnostic and therapeutic decision-making in general practice. For the GP, they summarise the best management options for the average patient from a scientific point of view. At the same time, the patient needs to be involved as an equal partner in decision-making. Communication must be improved to ensure clear questions from the patient to the GP and adequate transmission of information from the GP to the patient about all aspects of the different management options. This can result in a reasoned, joint responsibility patient-GP decision to opt for a different best choice of treatment. For practical reasons, this alternative is explicitly highlighted here, but will not again be examined separately in the guidelines.
1. INTRODUCTION
1. 1. Problem description and substantiation of the guidelines
Diabetes is a significant health problem of increasing incidence. Diabetes leads to significant complications: acute complications like hypoglycaemia, hyperglycaemia and ketoacidosis, but also chronic complications such as eye problems, nephropathy, neuropathy and foot problems. Type 2 diabetes patients are also at increased risk of cardiovascular disease. The above is accompanied by significant mortality and physical and psychosocial morbidity.
Prevention and treatment of diabetes complications involve extremely high direct and indirect costs both for the patients and for society at large (1). Large scale research (2) and trials in specific target groups (3) provide incontrovertible evidence that strict monitoring and treatment of Type 2 diabetes can significantly reduce the scope and impact of complications.
Providing care to diabetes patients is a highly complex matter:
Diabetes care is a multifaceted issue, involving education and advice on diet and exercise, development of therapeutic objectives, treatment of hyperglycaemia, monitoring cardiovascular risk factors, detection and treatment of chronic complications.
A number of multidisciplinary care providers, each making specific contributions, are involved. In the monitoring and treatment of Type 2 diabetes, first-line care plays an important role (4). This multidisciplinary approach requires a clear definition of responsibilities and good cooperation between providers ("shared care").
Diabetes patient care requires a sustained effort. Once the diagnosis has been made, the patient must first and foremost make changes in his or her lifestyle. If applicable, the primary recommendations include smoking cessation, weight reduction, appropriate diet and more exercise. Complex treatment with various hypoglycaemics or insulin in combination with a number of other medications is often unavoidable. In addition, patients also often find it difficult closely to follow the proposed therapy (5).
Hereditary predisposition is important in this condition, but lifestyle also plays a crucial role. In particular abdominal obesity and lack of physical exercise are triggering factors. The risk of developing the disease increases with age. The condition generally manifests itself in middle age or older (whence the name formerly used to describe the disease, "old age diabetes"). Sometimes the disease is diagnosed following the appearance of symptoms of hyperglycaemia, but such symptoms only appear in acute cases. Mostly, this type of diabetes is discovered as a result of preventive examinations in at-risk patients, or following complaints as a result of developing micro or macrovascular complications.
In the years following diagnosis of Type 2 diabetes, there is a progressive decline in the number of beta-cells while insulin resistance continues to rise slightly. This gradual decline means that, over time, more and more medication is required for glycaemic control. In addition, over the long term most Type 2 diabetes patients need to be started on insulin.
The insulin resistance of Type 2 diabetes has many consequences that go far beyond the metabolism of carbohydrates. It is associated with abdominal obesity, hypertension, dyslipidaemia, hyperuricaemia and hypercoagulability. A number of epidemiological studies have shown that this "insulin resistance syndrome" or "metabolic syndrome" goes hand in hand with strongly increased cardiovascular morbidity and mortality (6). The treatment of Type 2 diabetes therefore involves more than mere control of blood glucose values. A broad cardiovascular approach becomes essential with diabetes patients.
For all the above reasons it makes sense to issue guidelines on diabetes mellitus, and more particularly on early detection, diagnosis, treatment and management. Since the first interdisciplinary consensus on the management of "non-insulin dependent diabetes mellitus" in Flanders (7), new scientific evidence has become available on the prevention, diagnosis and treatment of diabetes. This brings about the need for a review that will take into account these new scientific research results.
Since at this time there is a structural lack of quality indicator data as concerns diabetes care in Belgium, it is not possible to stipulate clear objectives in the field of processes and outcomes in diabetes care among other areas. However, this set of good practice guidelines is a useful point of reference and departure for the improvement of the quality of care of people with diabetes.
1. 2. Definitions
Diabetes mellitus is a metabolic disease characterised by an increased blood sugar level (hyperglycaemia), resulting in disorders of the carbohydrate, fat and protein metabolic functions. The condition is due to a defect in the secretion of insulin, the effect of the insulin, or both.
Type 1 diabetes (8) is an autoimmune disease characterised by the destruction of pancreatic beta-cells. Through the resulting lack of insulin, administration of this hormone becomes essential. This form of the disease usually manifests at a younger age. It is usually diagnosed upon onset of acute symptoms.
Type 2 diabetes is usually the result of a dual problem: on the one hand there is resistance of the peripheral tissues against insulin (insulin resistance), and on the other hand the cells can still produce insulin, but are unable to compensate for the insulin resistance.
Pregnancy, or gestational, diabetes is diabetes that develops during pregnancy. In many cases, this type of diabetes disappears after the end of the pregnancy. This type of diabetes not only has adverse effects on the foetus, but is also a precursor of Type 2 diabetes in the mother.
Impaired glucose tolerance (IGT) and impaired fasting glucose (IFG) (9) are elevated blood glucose conditions that do not yet correspond to the diagnostic criteria for diabetes. They increase cardiovascular risk and the risk of developing diabetes (cf. also 3. 1).
Metabolic syndrome (or insulin resistance syndrome) is a metabolic disorder consisting of a combination of abnormal blood glucose levels, high blood pressure, obesity, and atherogenesis and dyslipidaemia (low HDL cholesterol and high triglyceride levels). Currently, metabolic syndrome is diagnosed according to International Diabetes Federation (IDF) criteria in the presence of abdominal obesity and two concurrent factors out of a list of four (10). In Caucasians, abdominal obesity is defined as a waist girth >=94 cm for men and >=80 cm for women.
Additional factors:
Triglycerides: >=150 mg/dl (1. 7 mmol/l) or appropriate treatment;
HDL cholesterol <40 mg/dl (1. 0 mmol/l) or appropriate treatment;
Blood pressure: systolic >130 mmHg or diastolic >85 mmHg or appropriate treatment;
Fasting plasma glucose >100 mg/dl (5. 6 mmol/l) or Type 2 diabetes diagnosed at an earlier stage.
Secondary diabetes (11) is a form of diabetes in which another disease is at the root of the development of the diabetes. The most frequent causes of secondary diabetes are:
Diseases of the pancreas: pancreatitis (alcohol abuse), neoplasia
Metabolic conditions: hemochromatosis
Endocrine disorders: hyperthyroidism, Cushing's syndrome, acromegaly, etc.
Use of diabetogenics: diuretics, corticosteroids, nicotinic acid, etc.
MODY or "Maturity Onset Diabetes of the Young" is a relatively frequent special form of Type 2 diabetes that occurs at an early age (before age 25) and which is hereditary as an autosomal dominant characteristic. A recent British study demonstrated that approximately one out of every two children presenting with a clinical picture of Type 2 diabetes are afflicted by a form of MODY (12). A number of genetic defects have been found to be at the origin of this condition (13).
LADA or "Latent Autoimmune Diabetes of Adults" is a special, slowly developing form of Type 1 diabetes (14). Diagnosis sometimes only becomes obvious because treatment started with oral antidiabetics has little effect and the patient continues to complain of hyperglycaemia. In such cases, referral to a multidisciplinary diabetes team will become necessary.
MIDD or "Maternal Inherited Diabetes and Deafness" is a syndrome that should be taken into consideration when faced with a combination of diabetes and deafness (15). It is a mitochondrial genetic defect that can only be transmitted through the maternal line.
These recommendations refer exclusively to Type 2 diabetes mellitus in adult patients.
1. 3. Epidemiology
Diabetes mellitus is an important health problem of worldwide incidence. The number of diabetes patients is on the rise everywhere in the world. In 2001, the "International Diabetes Federation" (IDF) estimated the number of diabetes patients worldwide at 177 million (16). It is believed that in 2010 six per cent of the world's population will have diabetes (17). The World Health Organisation (WHO) forecasts 366 million diabetics by 2030 (18).
The prevalence of diabetes in Europe is estimated at 4% of the total population, but only half of all those affected are actually diagnosed. Type 2 diabetes patients account for more than 90% of this population. The incidence of Type 2 diabetes increases with age; more than 10% of all people over 65 are diabetics. Because in our society there are ever more obese children with inappropriate eating habits and who have very little physical activity, there is also a greater frequency of development of Type 2 diabetes in younger years (19).
The figures for Belgium are limited and partially incomplete. Every year, some 2,070 new Type 1 diabetes patients are diagnosed, 1,180 of whom are under the age of 14 and 890 are aged between 15 and 39 at the time of diagnosis. As concerns Type 2, some 23,500 new cases are diagnosed in Belgium every year (20). The prevalence of diabetes in Belgium (Types 1 + 2) is estimated at 5.2% of the total population, and that of IGT at 7.4% (21).
The prevalence of Type 2 diabetes can differ significantly depending on the ethnic composition of the population, with rates two to six times higher in allochthonous than in autochthonous populations (22). There are no figures available on the prevalence of Type 2 diabetes in allochthonous populations in Belgium (23).
The prevalence of diabetes complications varies depending of the duration of the disease and glycaemic control. Macrovascular and microvascular diseases are the most important causes of diabetes related morbidity and mortality. Diabetes is the most significant cause of blindness in adults, of non-trauma related lower limb amputation, and of kidney failure resulting in transplantation and dialysis. In addition, the risk of coronary heart disease is two to four times higher in diabetes patients and the risk of stroke or peripheral vascular disease is also strongly increased (24).
1. 4. Issues at stake
These recommendations aim to provide an answer to the following issues:
Which factors make diabetes screening desirable, and how should it be carried out?
What are the criteria for formulating a diagnosis of diabetes mellitus?
What treatment objectives are assumed in diabetes mellitus patient care?
What constitutes useful advice in connection with diet and exercise?
How is the treatment of hyperglycaemia in Type 2 diabetes patients managed?
What risk factors are monitored to prevent cardiovascular complications?
How can chronic complications (nephropathy, neuropathy, retinopathy, foot problems, cardiovascular complications) be detected and treated in their early stages?
What is involved in a good diabetes education aimed at increasing "patient empowerment" (25)?
How can diabetes patient care be organised along the principles of "shared care"?
2. EARLY DETECTION
2. 1. Early detection of Type 2 diabetes
2. 1. 1. Justification
A number of arguments speak in favour of earliest possible diagnosis of Type 2 diabetes:
Diabetes is a serious disease of very frequent occurrence.
It involves a long asymptomatic period. Population research shows that between 1/3 and 1/2 of all people with diabetes have not been diagnosed (26).
On the basis of the presence of diabetic retinopathy (a disorder that is specific to diabetes), scientists are able to calculate that at the time of diagnosis the patient has often been affected by the disease for more than ten years (27). Insulin resistance syndrome, which is frequently at the root of Type 2 diabetes, and which significantly increases cardiovascular risk, is often found to have been present for an even longer period of time.
The prevalence of Type 2 diabetes is shifting to a younger age. There have even been cases reported of Type 2 diabetes in children with morbid obesity.
Unidentified diabetes is not a benign condition: at the time of diagnosis, chronic complications are often found to be present in a more or less developed form.
The disease can be diagnosed by means of a simple and inexpensive blood test.
Treatments of proven efficacy in the prevention of further complications are available.
It can therefore be expected that prognoses will improve as a result of earlier detection. However, to date there is no formal evidence to substantiate this presumption (28).
2. 1. 2. Strategy
A screening of the entire population (29) is not recommended due to an unfavourable cost-benefit ratio (30). On the other hand, targeted, opportunistic screening of persons at distinctly increased risk of Type 2 diabetes is recommended (31). Obviously, such screening would be best envisaged as part of a global cardiovascular prevention strategy. The GP is in a good "case finding" position in connection with patient consultations.
2. 1. 3. Which risk groups?
The following risk groups should be taken into consideration:
People with a prior history of blood glucose disorders (e. g. gestational diabetes, stress hyperglycaemia due to surgical interventions);
People treated with certain medications (32) (e. g. corticoids, atypical neuroleptics (33), protease inhibitors, etc. ) or suffering from certain conditions that may cause diabetes (e. g. pancreatitis, alcoholism);
People aged 45 and over with a family history of first-degree relatives diagnosed with Type 2 diabetes;
People aged 45 and over with signs of metabolic syndrome;
People aged 65 and over, regardless of whether or not any additional risk factors are present.
Naturally, people with symptoms or complaints suggesting Type 2 diabetes (thirst, recurring urogenital infections, signs of diabetes complications etc. ) should also be tested. Such cases, however, can be considered to fall within the "diagnostic" rather than "screening" category.
2. 1. 4. Which test and how often?
A measurement of fasting blood glucose is recommended. Ideally, laboratory assays of venous blood should be used (34).
Obviously, treatment should be started immediately if diabetes is found.
With impaired fasting glucose (IFG) or impaired glucose tolerance (IGT) (cf. diagnostic criteria, Section 3. 1) annual screenings are recommended. If glycaemia levels are within the normal range, it is advisable to repeat the test every three years. Where there is a history of gestational diabetes or stress hyperglycaemia, the test should be repeated on an annual basis. Regardless of the results of the screening test, the controllable risk factors must be treated, both in order to reduce cardiovascular risk and in order to prevent or delay the development of such factors into fully-fledged diabetes (35).
2. 2. Early detection of gestational diabetes
Gestational diabetes is defined as a glucose tolerance disorder developed during pregnancy. The prevalence of gestational diabetes varies between 1 and 14% of all pregnancies, depending on the population studied and type of diagnostic test used.
Gestational diabetes increases the risk of macrosomia, with its associated perinatal complications such as hypoglycaemia and birth trauma (shoulder dystocia, fractures, peripheral nerve damage etc. ) (36). There are also potentially longer-term adverse effects for both the mother and the child (37).
In view of the importance of these issues for both mother and child, screening for gestational diabetes is also recommended, unless the risk is so small as to be negligible.
The risk of gestational diabetes should be evaluated during the very first consultation.
The risk factors are (38):
BMI >25 kg/m2 (in particular waist girth at the level of the navel of >88 cm) prior to pregnancy
Positive family history of Type 2 diabetes in first-degree relatives
Age >25 years
Multiple pregnancy
Earlier gestational diabetes
Children with high weight at birth (>=4.5 kg)
Earlier IFG with FPG = 100-125 mg/dl (5.5 - 7.0 mmol/l)
Earlier IGT with OGTT 2-hour value 140-199 mg/dl (7.8 - 11.0 mmol/l)
If none of these risk factors are present, the screening procedure can be omitted. In the presence of at least one risk factor, the best time for screening is between pregnancy weeks 24 and 28.
If at the first contact there already appears to be a strongly increased risk (marked obesity, history of gestational diabetes, glucosuria or strong family history of diabetes), the screening should take place directly upon first contact. If this screening test is negative, a new screening test is then performed between weeks 24 and 28. The test is always performed on venous plasma. The use of glucose meters is not advisable for screening purposes (cf. above).
2. 2. 1. How to screen?
There are various different screening methods (39). We suggest screening for gestational diabetes on a venous blood sample drawn one hour after stressing with 50 g glucose (= challenge test). This test can be performed at any time of the day and the woman is not required to be fasting at the start of the test. In addition, this test method appears to be the most cost effective (40).
The screening test is positive if one hour after intake of the 50 g glucose, glycaemia is measured at >=140 mg/dl (7. 8 mmol/l). The diagnosis of gestational diabetes should then be confirmed by means of an OGTT.
2. 2. 2. Diagnosing gestational diabetes
Final diagnosis of gestational diabetes is made by means of an OGTT (41). This involves glucose stress of 100 g following 8 to 10 hours overnight fasting.
The cut-off values are:
fasting >=95 mg/dl (5.3 mmol/l)
1 hour >=180 mg/dl (10.0 mmol/l)
2 hours >=155 mg/dl (8.6 mmol/l)
3 hours >=140 mg/dl (7.8 mmol/l)
The test is positive if two or more cut-off values are exceeded.
If gestational diabetes is diagnosed, the patient should be referred to a multidisciplinary diabetes centre. With adequate treatment there is significant reduction of perinatal morbidity (42).
2. 3. After the pregnancy
The risk that a patient with gestational diabetes will develop Type 2 diabetes after her pregnancy is of between 30 and 60% (43). For this reason, following a diagnosis of gestational diabetes it is best to screen on an annual basis for Type 2 diabetes (cf. above), and certainly in the event of overweight or other risk factors. It is very important to identify this risk group in a timely manner in order to treat such risk factors as obesity and lack of physical exercise.
3. DIAGNOSIS OF DIABETES MELLITUS
3. 1. Diagnostic criteria
For basic information please refer to the criteria of the American Diabetes Association (44). They suggest using fasting glucose determined in venous plasma in clinical practice. The test is easy to perform, patient friendly, inexpensive and easily reproducible. Fasting means that the patient will not have consumed food (calories) for at least eight hours prior to the test. The oral glucose tolerance test (OGTT) is only recommended for research purposes, or to diagnose gestational diabetes (cf. section on early detection).
Fasting
A value of <100 mg/dl (5.5 mmol/l) is normal. Values between 100 and 125 mg/dl (5.5 and 6.9 mmol/l) are referred to as "impaired fasting glucose" (IFG). This creates an increased risk of developing diabetes.
A fasting glucose value of >=126 mg/dl (7.0 mmol/l) can already indicate the existence of diabetes. In view of the impact of the diagnosis, confirmation is required if abnormal fasting glucose values are returned. Two measurements on different days are necessary before a final diagnosis can be made. The diabetes diagnosis is automatically confirmed with a repeat value of >=126 mg/dl.
Non-fasting
When measuring non-fasting glucose, values >=126 mg/dl (7. 0 mmol/l) must be checked by means of a fasting blood sample. Non-fasting glucose values of (>=200 mg/dl (11. 1 mmol/l) automatically indicate diabetes.
Medical stress (infection, trauma, surgery, medication, etc. ) can temporarily increase blood glucose levels. These values must then be measured again outside of the acute period. Patients with temporary "stress hyperglycaemia" must be monitored, as they are at high risk of developing diabetes (cf. section on early detection).
Table 1. Diagnostic criteria for Type 2 diabetes
Fasting
<100 mg/dL (5,5 mmol/L) normal
=100 mg/dL en <126 mg/dL (5,5 mmol/L en 7,0 mmol/L) impaired fasting glucose (IFG)
=126 mg/dL (7,0 mmol/L) diabetes mellitus
Not fasting
=126 mg/dL en <200 mg/dL (7,0 mmol/L en 11,1 mmol/L) repeat under fasting conditions
=200 mg/dL (11,1 mmol/L) diabetes mellitus
2 hours after stress with 75 g glucose (OGTT)
=140 mg/dL en <200 mg/dL (7,8 mmol/L en 11,1 mmol/L) impaired glucose tolerance (IGT)
=200 mg/dL diabetes mellitus
3. 2. Difference between Type 1 and Type 2 diabetes
A number of clinical parameters are used in order to differentiate between Type 1 and Type 2 diabetes. They are summarised in the following flowchart.
It is not always simple to distinguish between Type 1 diabetes mellitus, Type 2 diabetes mellitus and secondary diabetes mellitus based on age, symptoms and glucose values. To the extent that the patient is younger and thinner and has higher blood sugar levels, there is a greater chance that Type 1 diabetes mellitus is involved.
In Type 1 diabetes mellitus, the following specific symptoms are often in evidence: marked polyuria; polydipsia; weight loss and ketonuria. Type 2 diabetes mellitus can develop asymptomatically for a long time. Symptoms are often non-specific: fatigue, recurring infections; poorly healing wounds. Frequently the disease is diagnosed upon discovery of a diabetes mellitus complication (e. g. retinopathy, neuropathy).
4. TREATMENT OBJECTIVES
The goal of diabetes treatment is to promote the well-being of persons with diabetes to enable them to lead lives that are qualitatively and quantitatively equivalent to those of people who do not have diabetes.
Specifically, this means (45):
Preventing symptoms of hyperglycaemia,
Preventing acute complications (hypoglycaemia, hyperglycaemia),
Preventing chronic complications,
Reducing associated mortality,
Maintaining patient autonomy and self-reliance,
Fighting social discrimination.
In order to accomplish all the above, one should not concentrate exclusively on the treatment of specific diabetes related problems such as
Ensuring good blood glucose control
Early detection (at a reversible stage) of diabetes complications
but simultaneously fight the overall cardiovascular risk.
To do so, the following action must be taken:
Reducing excess weight if applicable (cf. Section 5)
Stimulating physical activity (cf. Section 5)
Discouraging smoking (cf. Section 7)
Treating hypertension (cf. Section 7)
Starting a statin if there are no concomitant cardiovascular risk factors (cf. Section 7)
Evaluating whether to start the patient on a low aspirin dose (cf. Section 7)
All these actions are discussed in greater detail in the following sections.
Strict goals have been assumed in connection with each of these risk factors (46). It is however impossible to formulate absolute and universally valid treatment objectives. In addition, these goals are considered to be "moving targets" which will undoubtedly change in the future. Evolving treatment goals will always be clearly identified in follow-up reports to this recommendation.
The most important issue is the achievability of these strict objectives. Keeping the overall quality of life and welfare and well-being of each patient on an optimal level remains of the utmost importance.
The table below shows clinical target values that can be attained by many people with diabetes (47). These goals will be discussed in greater detail elsewhere in this document.
Table 2. Goals
Goal Unit
Smoking cessation -
Weight reduction with obesity 5 à 10 % / 1 year -
HbA1c <7,0 %
Fasting glucose =125 mg/dL
Blood pressure <130/80 mm Hg
LDL-cholesterol (48) <100 mg/dL
Targeted blood pressure values are a little lower with nephropathy (<125 / 75 mmHg).
5. DIET AND EXCERCISE ADVICE
We will discuss diet measures and advice regarding physical activity for Type 2 diabetes patients in one and the same section as these two issues are closely related and the necessary patient education methods are quite comparable.
The objective of both measures consists, on the one hand, in preventing or delaying the onset of Type 2 diabetes and, on the other hand, in creating a foundation for the control of the most important treatment parameters in existing cases of diabetes: weight, blood pressure, glucose and lipid levels (49).
5. 1. Prevention of Type 2 diabetes
The presence of IFG, IGT or both is today considered to indicate a pre-diabetic condition. The detection of pre-diabetes is not a goal in itself, but it helps identify a population at (strongly) increased risk of developing Type 2 diabetes.
In this high-risk group, diabetes can be prevented by means of lifestyle changes (50). This requires substantial effort. The use of metformin is also effective in diabetes prevention, but lifestyle changes appear to be more effective still (51).
A recent literature review evaluated the possibilities to prevent diabetes by means of lifestyle changes in the general population (52). The findings are less clear, primarily due to methodological limitations.
Properly controlled studies involving one arm in which lifestyle changes were evaluated always demonstrated that significant effort was required in order to achieve even moderate change in eating and exercise habits (53).
5. 2. Treatment approaches to Type 2 diabetes
5. 2. 1. Diet counselling
The principles involved in diet recommendations are:
Calorie limitation for overweight patients;
A balanced and varied diet based on the rules of the diet triangle (54) (healthy eating) with specific ratios between carbohydrates, fats and proteins;
Diet products for diabetics seldom qualify for selection because they can contain too much fat as compared to standard products and they are also often rather more expensive. Low-calorie sweeteners are allowed,
Alcohol can be consumed in moderation (maximum of 2 drinks per day), with extra care in cases of obesity (55),
Limiting salt and healthy eating are recommended.
In cases of obesity, a weight loss of 5 to 10% suffices in order significantly to lower insulin resistance and improve glycaemic control (56). The same amount of weight loss also reduces blood pressure, cholesterol levels and overall cardiovascular risk (57).
Please refer to the subject specific recommendations as concerns obesity management (58).
When changing eating habits, it is important to take the patient's current habits as a point of departure. The diet pattern is recorded in an eating diary. Individual goals can then be discussed with the patient on the basis of the existing eating pattern. This process requires a lot of time and specific skills (59). For this reason it is recommended to work with a dietician in the management of the dietary habits of diabetes patients (60).
The GP continues to play an important role from the point of view of patient motivation (61).
Standardised referral and back-referral letters ensure that the necessary and appropriate information is exchanged. The Diabetes Passport and the related right to reimbursement for diet consultations with a dietician can have a threshold lowering effect (cf. Section 11. 1, The Diabetes Passport).
5. 2. 2. Physical activity
Generally it is recommended to do physical activity that increases the pulse rate and/or leaves the person slightly short of breath (fast walking, bicycling, using home exercise equipment, etc. ) on most days of the week for 30 to 45 minutes each time. Encouraging exercise has a better chance of success if only moderate effort is recommended that can easily be integrated into each individual patient's daily life. Existing co-morbidities must be taken into account when beginning a programme to increase physical activity (62).
Certainly in the case of obese patients it is best to increase physical activity only gradually (63). Going for a half-hour walk three times per week is a realistic starting point. Then the intensity (brisk walking) and frequency (almost every day of the week) can be increased (64). The long-term goal is to perform a moderate physical effort for 30 to 45 minutes almost every day of the week (walking, swimming, cycling etc. ) (65). Some potential side effects of increased physical activity are muscle and/or joint lesions and cardiovascular events (66).
If a patient selects to do strenuous physical activity, it should be considered first to perform a cardiac stress test. Sustained effort is permissible, as it hardly increases the absolute risk of sudden death at all (67). Any potential complications arising from such physical activity must be taken into account in selecting the type of exercise.
Both diet and exercise advice have a better chance to succeed if they are customised for the patient and are regularly repeated, reviewed and adapted. This structured approach requires a lot of time and specific expertise (68).
A combination of diet, behavioural and exercise advice is more effective in achieving weight loss and maintenance than any of these therapies by itself. Weight loss is primarily caused by dietary measures. A sustained increase in physical activity is important in order to maintain the weight loss (69).
6. PHARMACOTHERAPY FOR TYPE 2 DIABETES: Treating hyperglycaemia
Patients receiving intensive treatment for optimal glucose control experience fewer chronic diabetes complications (70). However, good glycaemic control is not enough for maximum prevention of complications (especially in the macrovascular area). For optimal effects, hyperglycaemia treatments must be integrated into multifactorial approaches including the correction of cardiovascular risk factors and early detection and treatment of complications. (cf. also Section 7, Monitoring Risk Factors to Prevent Cardiovascular Complications).
Type 2 diabetes is characterised by a progressive decline in the pancreas' ability to release insulin. The rate at which this decline takes place differs from patient to patient. To maintain good glycaemic control, the treatment doses must be increased gradually. It is important to explain this to the patient directly at the time of diagnosis. This prevents the patient from becoming discouraged when the therapeutic dose is increased (71).
Hyperglycaemia reductions are best monitored by means of the HbA1c value. The fasting glucose value and the self-test results can be used for day-to-day diabetes management. The treatment should be adapted whenever the therapeutic goal is not reached. The more the results deviate, the faster the adjustment should be made. There is no minimum HbA1c threshold value, so that the lower the value, the lower the risk of complications. Because Type 2 diabetic are less sensitive to insulin (insulin resistance) the risk of severe hypoglycaemia is lower than in patients with Type 1 diabetes (72). For this reason, with most patients it should be attempted to attain a low HbA1c value of less than 7%.
The diagnosis should be reviewed whenever the treatment appears to have little effect and the patient continues to complain of hyperglycaemia (73).
6. 1. Oral antidiabetics (OAD)
There are five classes of oral antidiabetics, each of which has its own specific advantages and disadvantages (cf. Table 4) (74):
Biguanides, which promote insulin function by lowering glucose production in the liver (75)
Hypoglycaenogenic sulfamides (sulfonylureas), which stimulate insulin release
Glinides (also known as meglitinides), which have the same effect as sulfonylureas
Glitazones (also known as thiazolidinediones), which reduce insulin resistance
Alpha-glucosidase inhibitors, which inhibit the intestinal absorption of glucose.
Biguanides and hypoglycaenogenic sulfamides are the drugs that have been used for the longest time in the treatment of Type 2 diabetes. Their action is well-known and they have proved effective in connection with hard endpoints. To date there have been no studies to research the effect of glinides and glitazones on the development of diabetes complications (76).
Metformin
In the absence of contraindications, metformin is a first choice in starting pharmacotherapy (77). It reduces insulin resistance by slowing down glucose production by the liver and by means of improving muscle uptake of glucose. Metformin inhibits weight gain, does not cause significant hypoglycaemia, is inexpensive and inhibits cardiovascular complications in obese patients (78).
An extremely rare but sometimes lethal adverse effect of metformin is lactic acidosis. For this reason, metformin is contraindicated in situations in which the production of lactic acid can strongly increase or its clearance is impaired (79). Impaired kidney function (starting at creatinine >=1.5 mg/dl in men and >=1.4 mg/dl in women) (80) is therefore a contraindication for metformin.
Sulfonylureas
Sulfonylureas are a good second choice. In the UKPDS study they were also proven to reduce the onset of microvascular diabetes complications, and they are relatively inexpensive. Sulfonylureas stimulate insulin release by the pancreatic beta-cells. A potential danger when using sulfonylureas is the possibility of hypoglycaemia (81).
Glinides
Glinides (repaglinides) are related to sulfonylureas (82). Over the long term, the effects of glinides are perhaps highly comparable to those of sulfonylureas (83). Repaglinide is a fast-acting agent. Therefore there is little risk of developing hypoglycaemia. As are fast-acting sulfonylureas, glinides are a good choice for patients whose lifestyle involves an irregular schedule, and for patients in whom hypoglycaemia must absolutely be prevented (e. g. professional drivers). Owing to their rapid action, glinides must be taken with every meal. However, the drug need not be taken if a meal is skipped.
Glitazones
Glitazones improve insulin sensitivity in fatty tissues and in the liver (84). Their blood glucose lowering action is gradual and reaches its maximum after approximately 6-12 weeks. Glitazones have potentially positive cardiovascular effects as they influence various components of the insulin resistance syndrome (85). However, they induce fluid retention, which can aggravate existing cardiac decompensation (86). To gain an appropriate impression of the place of glitazones in treatment, it is necessary to compare the association glitazones + metformin or glitazones + sulfonylureas with another association or with insulin, which has not been done yet.
Acarbose
Acarbose, an alpha-glucosidase inhibitor, impedes the split of oligosaccharides and polysaccharides in the small intestine, thus inhibiting glucose uptake. This compound is not often used as it is not very strong and often causes intestinal stress due to the gases that develop in the bacterial breakdown of the not entirely digested saccharides in the colon. Acarbose is not reimbursed.
Since all the abovementioned products have approximately the same maximum glycaemia lowering effect (except for the weaker acarbose), there is no advantage in changing over to another product of the same class in the event of unsatisfactory performance (87). In such cases it is better to add a second oral antidiabetic (88), selecting a product with a different mechanism of action. The most frequently used combination in those cases is metformin and a sulfonylurea (89).
In a stable treatment situation, a combination drug can be used (90) to reduce the ultimate number of "pills" the patient needs to take. Fewer pills can lead to better treatment compliance.
If insufficient results are obtained with the combination of two oral antidiabetics, no time should be wasted by adding a third oral agent - in such cases it is better to switch directly to insulin.
Table 3
Class Generic name Products
Biguanides metformin Glucophage®, Metformax® and generics
Sulfonylureas
Rather fast-acting gliclazide Diamicron® end generic product
glipizide Glibenese®, Minidiab®
gliquidone Glurenorm®
Slow-acting glibenclamide Bevoren®, Daonil®, Euglucon®
glimepiride Amarylle®
gliclazide Uni-Diamicron®
Glinides repaglinide NovoNorm®
Glitazones pioglitazone Actos®
rosiglitazone Avandia®
Glucosidase inhibitors acarbose Glucobay®
Combination products glibenclamide + metformin Glucovance®
metformin + rosiglitazone Avandamet®
Table 4
Table 5
Posology Time of administration (81) Number of doses/day Initial dose rate of increase Maximum dose
Metformin during or after meals 2 1 x 500 mg
of 1/2 x 850 mg slow (1 x / week) 2 à 3 x 850 mg/d
Sulfonylureas fast acting productes 15-30 min. before a meal (less important with slow-acting products) 2 (Amarylle® and Uni-Diamicron®: 1) 1/2 tablet slow (1 x / week) 3-4 tablets/d (glimepiride 6 mg)
Repaglinide 15-30 minutes before a meal before each meal 1/2 mg/meal slow (1 x / week) 3 à 4 x 4 mg/d
Glitazones not related to mealtimes pioglitazone 1
rosiglitazone 1 to 2 1 tablet slow (1 x / week) 2 tablets/d
Acarbose at the start of the meal before each meal 1 x 25 mg slow (1 x / week) 3 x 100 mg/d
6. 2. Insulin
Insulin should be the drug of choice in the following situations:
Suspected Type 1 diabetes: important symptomatology (e. g. significant weight loss) and/or ketosis (ketones in blood or urine positive).
Very high fasting blood glucose of >300 mg/dl that does not immediately reduce with dietary measures. It can then be difficult, even in patients with Type 2 diabetes, to break the glucotoxicity cycle. After getting the glucose dysregulation under control with insulin, an attempt can be made to start oral antidiabetics.
Pregnancy (start directly at the time of planning the pregnancy). Oral antidiabetics are contraindicated with pregnancy.
Contraindications for oral antidiabetics.
Insulin is often temporarily required with acute glucose dysregulation as can be the case with infection, myocardial infarction, surgery, use of corticoids etc.
Switching to or adding insulin is necessary if it is not (any longer) possible to maintain glycaemic control with oral antidiabetics. In such cases it is possible either completely to switch over to insulin or to use insulin in combination with oral antidiabetics (92). It is generally easier to add insulin to an existing oral antidiabetic therapy than to start insulin monotherapy (93).
With most Type 2 diabetics it is primarily the fasting glucose that is difficult to control. When one insulin injection before bedtime is added in order to bring fasting glucose back to normal, daytime glycaemia can mostly still be kept under control for a significant period of time by means of oral antidiabetics (94).
Insulin can safely be started as a first-line therapy if a number of ancillary conditions are satisfied (cf. section on Ancillary Conditions) (95). These ancillary conditions are currently not fully met in Belgium. Thus self-care supplies are not reimbursed for patients in the transition to insulin therapy, or if only one insulin injection per day is required (96). As soon as the patient needs two injections, reimbursement takes place via the Diabetes Convention (97).
Recently, a possibility to involve a reference nurse when starting insulin as a first-line therapy was provided for (98). Referral to a specialised service is recommended if in spite of this help insulin cannot be started as first-line therapy in a timely and accurate manner.
Once an insulin regimen is started, it is the responsibility of the GP to monitor the results of the therapy and to adjust the insulin doses if applicable, taking into account patient glycaemia and HbA1c objectives.
Table 6: Types of insulin available
Class Insulin Brand name Action starts in Peaking after Active period
Ultrafast lispro insulin
aspart insulin Humalog®
Novorapid® 5-15 min.
5-15 min. 1 hrs
1 hrs 3-5 hrs
3-5 hrs
Fast regular insulin Actrapid®
Humuline Regular® 20-30 min.
20-30 min. 2 hrs
2 hrs 6-8 hrs
6-8 hrs
Intermediate NPH-suspension Insulatard®
Humuline NPH® 1-2 hrs
1-2 hrs 4-6 hrs
4-6 hrs 10-18 hrs
10-18 hrs
Slow zinc suspension
zinc suspension Monotard®
Ultratard® 1-2 hrs
4 hrs 4-6 hrs
6-8 hrs 10-18 hrs
20-24 hrs
Ultraslow glargine insulin
detemir insulin Lantus®
Levemir® 2 hrs
2 hrs none
3-4 hrs 24 hrs
18-24 hrs
Combinations* regular + NPH
aspart + aspart-protamine NPL Humuline® 30/70
Humuline® 50/50
Mixtard®10
Mixtard®20
Mixtard® 30
Mixtard® 40
Mixtard® 50
Novomix® 30 - - -
* In the combinations, the first figure in the brand name indicates the percentage of fast action insulin.
In Belgium, insulin preparations contain 100 IUs insulin per ml. The presentation is in vials for administration with insulin syringes or pumps, cartridges (or pen refills) for insulin pens or insulin pumps, and pre-filled disposable pens.
6. 3. Instructions for the correct use of insulin (99)
6. 3. 1. Storage of insulin
Unopened packages of insulin can be stored in a cool place (i. e. between 2 and 8°C) for a minimum of three years. Insulin, regardless of type, must not be frozen; when flying, it is recommended to take insulin in the hand luggage since the temperature tends to fall below freezing in airplane holds. Once a cartridge is introduced into a pen, it can be used for up to four weeks after installation. An insulin preparation that is in use is best not repeatedly placed in the refrigerator in order to prevent temperature fluctuations.
6. 3. 2. Administration of insulin
Insulin is injected subcutaneously into the arm, leg, buttocks or abdomen. Resorption speed is determined among other things by the vascularisation of the part of the body into which the injection is made, and is highest in the abdomen, lower in the buttocks, and lower still in the arm or leg. Insulin is best not injected into moles, birthmarks or paralysed limbs. Frequently, the vial or cartridge contains a mixture of insulins as a suspension. The consistency of the suspension must be homogeneous at the time of withdrawing the desired amount of insulin. When an insulin mixture, e. g. 30/70, is not sufficiently homogenised prior to administration, there will be a significant difference in the effect of the first and the last few millilitres of the contents of the vial. Insulin can be homogenised by agitating by inversion of the vial or pen at least ten times; standard shaking is not enough. In performing the injection, after having fully depressed the plunger of the syringe, it is necessary to wait for 5 to 10 seconds before withdrawing the needle to ascertain that all units have been injected.
6. 3. 3. Changing the injection site
In the administration of insulin it is important to change the injection site each time. In particular with the slower-acting drugs, lipodystrophy can develop if the same injection site is used too often. Injection into skin areas in which this symptom appears should be avoided for a few months.
6. 3. 4. Needle length
Given that the thickness of the skin of the abdomen, arms and legs varies, it can be useful to adapt the length of the needle employed accordingly. The desired needle length can be determined by taking a loose skin fold between thumb and forefinger to determine its thickness; the appropriate needle length is approximately half of this thickness.
6. 3. 5. Disinfecting the skin
Disinfecting the skin is not necessary. It should, however, be clean.
6. 3. 6. Changing the needle
There are different schools of opinion in regard to changing the needle when using insulin pens. Officially, it is recommended to use a new needle for each injection. On the other hand it is also posited that with multiple injections per day, using just one needle is acceptable.
6. 4. Administration using an insulin pen
The injection pen represents a simplification of the administration of insulin as it eliminates the need to perforate the vial. Pens are available under various different brand names. There are also pre-filled, disposable pens; the user merely needs to mount the needle on them. Not all insulins are appropriate for use in a pen; thus, for instance, insulin preparations that contain zinc are not suitable for use with this injection method.
Table 7. Insulin pen brand names
Humapen® Suitable for all 3 ml pen charges produced by Lilly: Humuline® (regular, NPH and mixtures) and Humalog®
Novopen 3® Suitable for all 3 ml pen charges produced by Novo: Actrapid®, Insulatard®, Novorapid®, Levemir® and Mixtard®-mixtures
Optipen Pro 1® Suitable for use with Lantus® products
Autopen 24® Suitable for all 3 ml pen charges produced by Lilly (see above) and for Lantus® products. The pen exists in 2 versions, one releasing 1 U, and another releasing 2 U per click.
This range of pens is regularly updated
7. MONITORING RISK FACTORS TO PREVENT CARDIOVASCULAR COMPLICATIONS
Cardiovascular conditions (100) are the most significant cause of morbidity and mortality in Type 2 diabetes patients (101). As compared to non-diabetes patients, Type 2 diabetes patients are at two to four times higher risk of death from cardiovascular causes (102). In a Finnish cohort study (7-year follow-up) the risk of experiencing myocardial infarction in Type 2 diabetes patients without a prior history of coronary conditions was the same as in non-diabetes patients with a prior history of coronary conditions (103). In acute vascular conditions there is often a significant diabetic dysfunction that is, in turn, associated with a poorer prognosis (104).
Most Type 2 diabetes patients are at high risk of cardiovascular conditions (105) and this means that with most patients an aggressive approach to the cardiovascular risk factors is indicated in addition to treating the hyperglycaemia.
There is also convincing evidence that a strict approach to cardiovascular risk factors can prevent or delay the onset of cardiovascular conditions in Type 2 diabetes patients (106).
7. 1. Managing cardiovascular risk
Approaches to cardiovascular risk are always multifactorial, addressing both the prevention of cardiovascular disease and the early detection of existing complications (107).
This approach always involves the following elements:
Smoking cessation
Seeking an achievable weight reduction for patients who are overweight or obese
Stimulating physical activity
Starting a statin (unless there are no additional cardiovascular risk factors) (108)
Trying to achieve optimal blood pressure
Trying to achieve optimal blood glucose levels
Considering starting acetylsalicylic acid
The approach is designed to manage all these risk factors in each diabetes patient, but always on an individual basis. Seeking to accomplish individually achievable and flexible goals helps prevent demotivation in both doctor and patient, which would result in the patient no longer undergoing optimal treatment.
The Diabetes Passport is a useful instrument to analyse the "controllable" cardiovascular risk factors with the patient and to agree on achievable targets. We are recommending repeating this analysis on an annual basis. In determining patient goals it is important to emphasise that every accomplishment, no matter how small, will result in significant advantages (109).
7. 1. 1. Smoking cessation
Smoking increases the risk of cardiovascular morbidity and mortality in diabetes patients (110). Even second-hand smoke is a significant and avoidable cause of ischaemic heart disease (111).
Stopping smoking is therefore an important measure for diabetes patients in order to reduce their cardiovascular risk (112).
Smoking cessation counselling begins with a clear and personal recommendation from the treating physician. At this time, only very few patients have the feeling that they are clearly being asked to stop smoking. There are different methods to help smokers succeed in the cessation process (113).
Smoking cessation counselling must be followed by ongoing support, ideally including the patient's immediate entourage.
7. 1. 2. Pursuit of an achievable weight reduction for patients who are overweight or obese
Weight reduction is an important treatment goal in cases where the patient is overweight or obese (114). A body weight reduction of 5 to 10% is considered to be an achievable goal. Moderate weight loss improves glycaemia, HbA1c and the cardiovascular risk profile (115). Long-term maintenance of the weight loss is more important than initial slimming (116). As regards the treatment of obesity, please refer to the relevant recommendation (117).
7. 1. 3. Stimulating physical activity
An increase in physical activity goes hand in hand with a reduction of cardiovascular risk. The goal is to do 30 to 45 minutes' moderate physical activity on most days of the week (118). Such physical activity is best built into the daily routine (e. g. walking) (119).
Physical exercise is also an important component of the weight reduction programme. While a limitation in calorie consumption primarily contributes to an initial weight loss, regular physical effort helps maintain the weight loss and prevent new gain.
7. 1. 4. Starting a statin unless there are no attendant cardiovascular risk factors
Lipids control is an implicit component of the follow-up of diabetes patients. It is recommended that the values of cholesterol (both HDL and LDL cholesterol) and triglycerides in blood be measured on an annual basis. Fasting blood samples are required. Diabetes patients have a strong post-prandial rise in the level of triglycerides, which also increases their cholesterol levels (120). LDL and HDL cholesterol are independent risk factors for coronary disease in diabetes patients too (121).
Treatment with a statin, aimed at reducing LDL cholesterol, significantly lowers cardiovascular risk both in patients with and without a history of cardiovascular disease (122). The reduction takes place regardless of the initial lipid values, i. e. also in lipid profiles that would normally be considered to be favourable. In considering whether to start a statin the patient's overall risk profile therefore carries more weight than the lipid values themselves (123). This means that most Type 2 diabetes patients will be started on a statin (124).
At the moment there is insufficient evidence as to the target values to be favoured. Goals are set by consensus. When a statin treatment is started within the scope of a lipids disorder, the currently proposed LDL cholesterol value is <100 mg/dl. In secondary prevention, it is argued that the target value should be <70 mg/dl (125).
There are no treatment goals for HDL cholesterol and triglycerides, but these values are nonetheless used to help evaluate cardiovascular risk (126).
Increased triglycerides and low HDL cholesterol are initially approached via diet recommendations, physical exercise and optimisation of glucose control. On the pharmacological level, fibrates are more effective than statins as concerns triglycerides and HDL cholesterol. However, there are no large randomised studies of diabetes patient populations examining the effect of these products on hard endpoints. For this reason the use of statins should be a preferred choice in the treatment of Type 2 diabetes at increased cardiovascular risk (127).
In the event of complaints and symptoms that could be indicative of muscle involvement, after starting a statin or fibrate it is advisable to determine the creatinine kinase (CK) level within the scope of a myopathy or rhabdomyolysis. The treatment should be suspended if CK levels reach a point greater than five times the normal value (128). Determining the CK level in patients without muscle complaints is not productive, except in patients at increased risk already prior to starting the statin.
In starting a statin and/or a fibrate it is also recommended to check liver function. The treatment should be suspended if transaminases increase to reach three times the normal level.
7. 1. 5. Trying to achieve optimal blood pressure
Blood pressure control is another essential component of the follow-up of Type 2 diabetes patients (129). It is recommended to check blood pressure every three months. At present, there is convincing evidence that keeping a tight control on blood pressure significantly reduces the risk of cardiovascular morbidity and mortality in Type 2 diabetes patients. This also applies to patients with isolated hypertension and to older diabetes patients (130).
International recommendations currently advocate consensus target blood pressure values of <130 mmHg systolic and <80 mmHg diastolic (131). The lowest attainable systolic value can be aimed for, as there is no threshold value under which there are no further complications. Diabetes complications systematically increase along with an increase in systolic blood pressure (132). Evidence that a diastolic blood pressure of =80 mmHg is desirable is provided by the results of the HOT study (133).
At first, non-medication measures are implemented for high blood pressure: weight reduction, exercise, smoking cessation, moderate salt limitation and moderate alcohol consumption. There is no evidence in regard to these measures as applied to diabetes patients. In patients with essential hypertension, however, it has been sufficiently proven that these measures are effective in lowering blood pressure (134).
If non-drug measures fail, it is necessary to start pharmacotherapy. ACE inhibitors, diuretics, beta-blockers and calcium antagonists significantly lower cardiovascular mortality and morbidity in hypertensive diabetics (135). The different classes described above all have approximately the same blood pressure lowering effect, i. e. an expected average blood pressure reduction of 10 to 20%. There are no good long-term studies available on the effect of alpha blockers and antihypertensive drugs with central action.
Patients with micro-albuminuria should be started on an ACE inhibitor. If the therapy is not well tolerated, the patient should be started on an angiotensin-II-receptor antagonist because these types of drug inhibit the progression of nephropathy (136).
Standard indications and contra-indications apply in selecting whether or not to start the patient on a specific class. Please refer to the subject specific recommendations on hypertension (137).
Monotherapy is often not enough to attain optimal blood pressure target values. In such cases, a combination of different classes will be necessary (138). Whether the target value is attained will depend on a number of different factors, e. g. the starting blood pressure and the appearance of side effects (e. g. orthostatic hypotension).
7. 1. 6. Trying to achieve optimal blood glucose levels
Evidence for the relationship between glycaemic control and cardiovascular diseases is primarily found in observational studies. The relationship between hyperglycaemia and macrovascular complications is not as strong as the relationship with microvascular complications (139).
In obese patients, strict glycaemic control with metformin leads to more significant risk reduction for diabetes related endpoints than a treatment with sulfonylureas or insulin, perhaps because this product provides additional cardiovascular protection by lowering insulin resistance (140).
7. 1. 7. Acetylsalicylic acid
Platelet aggregation disorders are often found in Type 2 diabetes patients. The platelets of diabetes patients are hypersensitive to platelet aggregation substances. The most important factor is probably an increased production of thromboxanes. Aspirin blocks the formation of thromboxanes.
There is evidence that the intake of low doses of aspirin in secondary prevention and in high-risk patients reduces the risk of cardiovascular disease. The positive effect of aspirin is however less pronounced in diabetes patients than in non-diabetics (141).
Based on current evidence we would advise an aspirin derivative in low doses (75 - 100 mg) in Type 2 diabetes patients in secondary prevention. More data is required before aspirin use can generally be recommended to diabetes patients in primary prevention (142).
Treatment with acetylsalicylic acid does not increase the risk of vitreous body or retinal bleeding (143). The contraindications for aspirin treatment include allergy, bleeding diathesis, anticoagulation therapy, recent gastro-intestinal bleeding and clinically active liver disease. There is insufficient evidence to indicate that other anti-aggregants such as clopidogrel are safer, although clopidogrel is perhaps just as safe and effective as acetylsalicylic acid (144). A combination of acetylsalicylic acid and clopidogrel increases the risk of major bleeding in patients recently having experienced an ischaemic CVA or TIA and who have at least one other cardiovascular risk factor (145).
7. 2. Early detection of cardiovascular disease
Looking for symptoms (146) of vascular disease and clinical signs of vascular problems (pulsations, vascular murmurs) is part of the routine check-up to be practiced on diabetes patients. However, many diabetes patients develop signs of "silent ischaemia" without any classical angina symptoms. Therefore, asking the patient about "angina equivalents" such as marked shortness of breath or nausea with effort should be systematically undertaken.
We recommend an "at rest" ECG upon diagnosis of Type 2 diabetes mellitus. This test can be useful as a reference point in the event of later heart complications. The evidence available at the moment is insufficient in order to repeat an at-rest ECG on an annual basis in all diabetes patients.
There are no validated data available on the usefulness of systematic screening with technological resources (duplex, stress ECG, etc. ) for asymptomatic vascular disease in diabetes patients. Such tests are recommended only when there is a clinical presumption of the existence of this type of disease.
8. ACUTE AND CHRONIC COMPLICATIONS (detection and treatment)
8. 1. Acute complications
8. 1. 1. Hypoglycaemia
Diagnosis
Hypoglycaemia is due to an excessive level of insulin in blood and results in exceptionally low glucose values. Hypoglycaemia is defined as an event in which the typical symptoms of hypoglycaemia are combined with a plasma glucose concentration of <=70 mg/dl (3.9 mmol/l) (147).
The symptoms are of both adrenergic and neuroglycopenic nature. Adrenergic symptoms include, among others, perspiration, shivering and palpitations. Neuroglycopenic phenomena include concentration problems, behavioural disorders, changes in consciousness and, ultimately, coma. The adrenergic disorders can be masked by the use of some drugs such as beta-blockers.
In older patients, hypoglycaemia occasionally manifests in an unusual manner such as temporary paresis, CVA-like clinical symptoms, behavioural disorders or confusion. These neuroglycopenic pictures can sometimes be very misleading.
Hypoglycaemia significantly occurs exclusively in patients taking sulfonylureas, glinides or insulin. When the treatment consists exclusively of diet, metformin, glitazones or alpha-glucosidase inhibitors, the risk of hypoglycaemia is more negligible.
Because most Type 2 diabetics have insulin resistance, they are less at risk of hypoglycaemia than Type 1 diabetics (who are generally highly sensitive to the action of exogenously administered insulin). For this reason, with Type 2 diabetes it is generally possible to aim for stricter glycaemic control than with Type 1 diabetes. Physicians must avoid being excessively careful with blood sugar lowering medication out of fear of hypoglycaemia.
Factors that increase the risk of hypoglycaemia
Skipping a meal
Unusual physical effort
Alcohol use, in particular without food
Sulfonylureas with long-term action (especially glibenclamide)
Sulfonylurea use with impaired kidney function
Sulfonylurea interference with other drugs (sulphonamides, certain NSAIDs, fibrates, coumarin derivatives)
Insulin treatment
Approach
Hypoglycaemia requires immediate treatment. If analytical material is available, a blood glucose determination should first be performed in order to confirm the diagnosis.
The following steps should be taken with a patient who is still conscious:
Administer fast carbohydrates (10 to 15 g): give two to three sugar lumps, three to five tablets grape sugar, one half glass of a soft drink or fruit juice (no "light" products) (148).
It usually takes 10-15 minutes for the symptoms to disappear. The previous step can be repeated if necessary.
Then, slow carbohydrates should be consumed (e. g. a slice of bread, a piece of fruit or a glass of milk).
Patients with distinctly reduced consciousness should be managed as follows:
No oral carbohydrates due to the danger of aspiration pneumonia,
One ampoule intravenous hypertonic glucose (preferably 20 ml glucose 30% = 6 g), repeating if necessary; or 1 mg glucagon (Glucagen®) by subcutaneous, intramuscular or intravenous administration (149).
Oral carbohydrates as soon as the patient regains consciousness.
Hypoglycaemias induced by the slower-acting sulfonylureas and/or insulins can be highly refractory and recurrent. In these circumstances, the action of glucagon is also less effective. It is therefore important in such cases to monitor the glucose levels for 24 hours. Often, a longer period of glucose infusion may become necessary, even requiring the patient to be admitted to hospital.
Education
Patients treated with sulfonylureas and/or glinides must be educated about the prevention and treatment of hypoglycaemia. In doing so, it is useful also to involve family members.
Such education should cover the following subjects:
How can you prevent hypoglycaemia? (e. g. not skipping meals, extra snack in case of physical effort),
How can you recognise the symptoms of hypoglycaemia?
How can you correct a hypoglycaemia all by yourself?
Education on the use of glucagon is generally not necessary in cases of Type 2 diabetes (as opposed to Type 1 diabetes in which the risk of hypoglycaemic coma is much higher).
8. 1. 2. Hyperglycaemia, risk of ketoacidosis
Diagnosis
Glucose dysregulation can happen quickly when the patient is acutely ill. These situations most frequently come about as a result of infectious diseases such as the flu or urinary infections. Corticoid therapy too can cause a dysregulation.
The symptoms of the intercurrent disease often displace the clinical signs of the diabetes dysfunction. Therefore, glucose levels must also be monitored in the event of intercurrent disease.
Approach
Treat the intercurrent condition
Control the glucose levels. In view of the fact that the risk of developing ketosis-ketoacidosis is not significant with Type 2 diabetes it is not necessary to measure ketones, unless the patient experiences strong vomiting and/or seems very ill
In the event of persisting significant hyperglycaemia, oral antidiabetics should temporarily be increased, or insulin treatment should be started, or the existing insulin dose should be increased on a temporary basis
Ensure sufficient liquid intake
The need for hospitalisation is determined, among other things, by:
The opportunity to ensure that the necessary fundamental conditions for blood glucose monitoring and insulin administration (availability of family members or home care) are met,
The seriousness of the patient's condition,
The need for parenteral fluid administration: vomiting and polyuria can quickly result in dehydration and require parenteral therapy.
Education
The education programme aimed at Type 2 diabetes patients should include guidelines regarding the action to be taken in connection with hyperglycaemia and illness:
If already instituted, ensure stricter glucose self-monitoring,
Ensure adequate fluid intake (water, tea, broth),
Consume milk or lightly sugared drinks if it is difficult to ingest solid food,
Do not interrupt the treatment with oral medication or insulin, but, rather, consult a doctor,
Make sure to involve a doctor in a timely manner, certainly if food intake is affected, or if you experience vomiting, fever or changes in consciousness.
8. 2. Chronic complications
Some of the problems described below can also occur entirely independently from diabetes mellitus, but they are much more frequent with diabetes (e. g. cataracts); others are specific to diabetes (e. g. retinopathy, nephropathy).
8. 2. 1. Retinopathy
Diabetic retinopathy continues to be the most frequent cause of acquired blindness in Western countries in the 25 to 75 age group (150). Strict blood glucose (151) and blood pressure (152) regulation can prevent retinopathy or slow its progression.
At the time of being diagnosed with Type 2 diabetes, 20% of all patients already have retinopathy lesions. The reason for this phenomenon is that often, at the time of diagnosis, the patient has already suffered from diabetes for several years.
In view of the fact that retinopathy can cause irreversible lesions long before there are subjective vision changes, systematic monitoring is essential. For this reason, the following examinations must be performed at diagnosis and annually thereafter:
Vision check-up for both eyes,
Retinal examination with dilated pupils in a darkened room,
Intraocular pressure measurement.
These examinations require special expertise and must therefore be performed by an ophthalmologist. Do not forget to inform the patient to arrange for transport, as vision may remain clouded for a few hours after the examination (as a result of the eye dilation drops).
Diabetic retinopathy is characterised by different degrees of microaneurisms, bleeding, exudates, venous changes, formation of new blood vessels and retinal thickening. The condition can affect both the peripheral retina and the macula. Depending on the seriousness of the patient's condition, the disease can be classified as either:
non-proliferative retinopathy (slight, moderate to severe)
proliferative retinopathy
If the macula (the central vision area) is affected, the condition is termed maculopathy. Except for slight to moderate non-proliferative retinopathy, the other stages require urgent attention and treatment.
Diabetic retinopathy is aided by poor diabetes regulation, hypertension and renal insufficiency. Early treatment of a diabetic retinopathy (using laser technology) can inhibit or stabilise the development of the disease in more than 50% of all cases (153).
8. 2. 2. Nephropathy
Approximately 20 to 30% of Type 2 diabetes patients develop microalbuminuria. Of this population, 20 to 40% develop distinct kidney disease with macroalbuminuria (154). Of this group, 20% will further deteriorate into renal insufficiency (155). This last figure is somewhat limited by the fact that many patients die from cardiovascular problems before kidney failure can occur.
Microalbuminuria is often already present at the time when Type 2 diabetes mellitus is first diagnosed, because the disease frequently has been present for years and because in Type 2 diabetes microalbuminuria is a less specific indicator of kidney disease.
Detection of microalbuminuria
The first sign of nephropathy is the presence of low but abnormal quantities of albumin in urine (microalbuminuria). Microalbuminuria should be monitored annually. The measurement can be performed in different ways, but in practice it is recommended to have a morning sample (first urine after waking up) analysed in the laboratory to determine microalbumin and creatinine levels (156). Microalbuminuria is the term used when albumin excretion is >30 mg/g creatinine. This test is reimbursable for diabetes patients.
The changing concentrations of albumin in urine require repeating a positive test before a diagnosis of persistent microalbuminuria can be made (cf. microalbuminuria monitoring schedule).
A number of factors (urinary tract infections, physical effort, fever, cardiac decompensation etc. ) can produce a false positive result.
Plasma creatinine levels should be checked annually in Type 2 diabetes patients under pharmacotherapy in order to be able to adjust the medication in a timely manner in the event of an impairment of the renal function.
Microalbuminuria monitoring flow-chart
Treatment of microalbuminuria
Whenever microalbuminuria is diagnosed, strict management is necessary in order to prevent further progression towards renal insufficiency. This includes:
Detection and treatment of cardiovascular risk factors:
Microalbuminuria is an important risk marker for cardiovascular disease and is associated with a two to three times higher risk of cardiovascular morbidity and mortality (157),
Strict blood pressure control
Hypertension accelerates the evolution towards renal insufficiency. Strict blood pressure control (blood pressure =130/80 mm Hg) inhibits development of the disease. In the event of microalbuminuria the patient should be started on an ACE inhibitor or an angiotensin-II-receptor antagonist (158). Only ACE inhibitors have been demonstrated to reduce mortality and are therefore the treatment of choice (159).
Strict glycaemic control
The protective effect of good glycaemic control on kidney health has been unambiguously demonstrated in Type 1 diabetes. Although two recent studies suggest a similar protective effect for Type 2 patients (160), there is however no hard evidence available for this theory to date.
Annual kidney function check-up by means of plasma creatinine determination
Referral to a specialist is desirable in the event of an evolution towards macroalbuminuria.
8. 2. 3. Neuropathy
After 25 years of suffering the disease, approximately half of all diabetes patients show neuropathies that are directly linked to the degree of metabolic control. Neuropathy can cause severe morbidity.
The most frequent form attacks the distal sensory nerves, manifesting with paraesthesias, pain and finally reduced sensation, usually symmetrically in the lower legs. The motor nerves (paresis) and the autonomic nervous system (impotence, gastroparesis, orthostatic hypotension, bladder retention etc. ) can also be affected.
Sensory neuropathy in the lower limbs significantly increases the risk of diabetic foot lesions (cf. Section 8. 2. 4 Foot Problems). Patients often do not realise that they have less sensitivity in their feet, so that screening becomes necessary. In addition, advanced neuropathy is irreversible.
Screening and detection
Accurate screening and detection require the following elements:
Targeted anamnesis:
Sensory nerves: paraesthesias, pain, numbness, foot lesions
Motor nerves: paresis
Autonomic nerves: impotence, gastroparesis, orthostatic hypotension, bladder retention
Clinical examination:
Careful examination of feet and monofilament sensitivity testing (cf. Section 8. 2. 4. , Foot Problems).
Electromyograms (EMG) are not useful in screening for peripheral neuropathy. The test can produce entirely normal results with painful sensory neuropathies and delivers inadequate information about the risk of diabetic foot lesions.
Treatment
With good glucose control, painful distal neuropathy can be reversible at an early stage (161). At more advanced stages the damage is irreversible. In those cases, good glucose control is still important in order to inhibit the progression of the neuropathy.
Analgesics (e. g. paracetamol 1g 4x/d) can ease the symptoms, but are often inadequate. In those cases, combination treatment with amitriptyline (Redomex®, Tryptizol®) can be helpful (162).
Treatment with vitamin B is helpful only in rare cases of vitamin B deficiency (pernicious anaemia, alcoholism). Long-term administration of high doses of vitamin B can itself induce neuropathy.
Referral to a specialist is desirable in the following cases:
Severe pain in the lower limbs, not responding to treatment with amitriptyline. In such cases, gabapentin (Neurontin ®) can be used as an alternative (163).
Distal neuropathy with atypical presentation (asymmetrical, significant motor component). Further examination (including EMG) is then necessary in order to rule out non-diabetic neuropathy,
Severe impairment of sensitivity in the feet (cf. "Foot Problems"). Further management in a diabetes foot clinic is then advisable,
Isolated mononeuropathy: e. g. paralysis of the eye muscles or severe muscular atrophy,
Signs of autonomic neuropathy, such as vomiting, diarrhoea, recurring urinary infections, postural hypotension, post-prandial fullness and signs of a "hypo" shortly after a meal (suggesting gastroparesis).
8. 2. 4. Foot Problems
Foot problems are a very frequent occurrence in diabetes (164). Diabetics with neuropathy and/or peripheral vascular disease are at increased risk of developing ulcerations, infections and/or gangrene in the feet. The risk of amputation is 15 to 45 times higher in these patients than in non-diabetics. Early screening of patients at risk, timely prevention and appropriate treatment of the foot problems can lead to a significantly improved prognosis.
Detecting increased risk
The risk of foot lesions is evaluated on an annual basis by means of a simple screening examination. This includes:
Careful inspection of the feet, paying particular attention to skin and nail changes, and including an evaluation of potential orthopaedic deformities.
Evaluation of static abnormalities in feet and toes: prominent metatarsal heads (often covered in callosities), hammer toes, hallux valgus (bunions), crossed toes, earlier amputations, Charcot foot (a fragmentation of the small bones of the foot with loss of the arch structure),
Detection of impaired sensitivity in the feet with a Semmes-Weinstein monofilament (165),
Detection of peripheral vascular disorders by asking about complaints of claudication and/or pain at rest (diabetics with neuropathies often lose these pain alarms) and by means of palpation of the arterial pulses in the feet. A foot that is erythematous while dependent but pale when raised is a sign of critical vascular disease.
The results of these findings and the prior history of foot lesions can be summarised as a risk score (cf. also Diabetes Passport).
Risk group 0 1 2a 2b 3 (one of these)
Neuropathie* no yes yes yes -
Orthopedische misvorming** no no slight* severe Charcot***
Vaatlijden no no no no yes
Vroegere voetwonde of amputatie no no no no yes
Risico low moderate high very high extremely high
* with a monofilament test: positive if 2 of the 3 pressure points are not felt
** orthopaedic deformities:
slight = prominent metatarsal heads with minimal callosities and/or supple hammer or claw toes and/or limited halux valgus <30°,
severe = serious orthopaedic abnormalities.
*** Charcot foot, a fragmentation of the small bones of the foot with loss of the arch structure, indicates a very high risc of developing diabetic foot lesions.
Approach
Table: Preventive management based on degree of risk
Risk group 0 1 2a 2b 3
Education 1 x/12 months =1 x/6 months =1 x/6 months =1 x/6 months =1 x/3 months
foot care none 1 x/month 1 x/month 1 x/month =1 x/month
Insoles none comfort custom custom custom
Shoes off-the shelf off-the shelf semi-orthopaedic (semi-)orthopaedic (semi-)orthopaedic
Medical check-up 1 x/12 months 1 x/6 months 1 x/3 months =1 x/3 months =1 x/3 months
The following preventive measures must be taken will all patients at increased risk:
Thorough education (see below),
Regular foot care by a pedicurist or podiatrist (166) (nail care, callous removal). In patients with orthopaedic abnormalities (starting with Risk Class 2a) it is best to involve a podiatrist (167),
Wearing good socks, stockings and shoes, both indoors and outdoors (168),
Regular foot examination and shoe inspection by a doctor: monitoring of the results of preventive measures, detection of callous, blisters, lesions and fungus infections (interdigital, nails).
Education
The following points are important in proper patient education (169):
Ensure good foot hygiene:
Wash feet thoroughly on a daily basis and dry properly (to prevent softening between the toes),
Prevent chapping (especially of the heels), use a hydrating cream,
Take care of the nails: they should be clipped straight to prevent in-growing, sharp edges should be filed away, preferably with a non-traumatic (cardboard) nail file (170).
Wear good socks, stockings and shoes, both indoors and outdoors (see above).
Avoid traumas:
Do not walk barefoot,
Avoid contact with heat sources,
Do not try to manage calluses and corns yourself but use a pedicurist or podiatrist instead,
Check shoes for roughness and foreign objects every time before putting them on,
'Compensate' for the reduced pain alarm with daily visual and tactile examination of the feet. If necessary, the help of a person living with the patient or of a home care professional should be sought,
Consult a doctor immediately if any blisters or lesions should appear.
Referral
Patients at strongly increased risk of developing foot problems (Risk Class 2b onwards) should be referred to a diabetes foot clinic at an early stage for a thorough evaluation of the problem (171).
Active foot problems such as ulcerations, infections or gangrene in diabetes patients should be considered to be serious problems and require urgent referral.
Incorrect treatment of a foot ulcer in a diabetes patient can lead to amputation. In a large percentage of cases amputations can be prevented by swift and appropriate treatment. The decision to perform an amputation should only be made following consultation with a multidisciplinary diabetes foot team.
8. 2. 5. Sexual Problems
In treating diabetes mellitus patients it can be useful to enquire about sexual dysfunctions in a tactful but thorough manner: erectile dysfunction in men (172) and inadequate lubrication, dyspareunia and reduced libido in women (173).
Because of the multiple factors involved in its etiopathogenesis, the treatment of erectile dysfunction often requires a multidisciplinary approach, which will necessarily include psychosexual counselling and a urologist's opinion. Hormonal dysfunction (prolactin, testosterone) should be ruled out. Often a treatment is started with oral phosphodiesterase inhibitors (174) such as: sildenafil (Viagra), vardenafil (Levitra) and tadalafil (Cialis). Patients should be warned about side effects such as headache, nasal congestion and dyspepsia. An absolute contraindication is the concomitant use of oral nitrates for coronary pathologies. If the oral therapy should fail, there are various options that can be added to the PDE5 inhibitor therapy (175).
There are no treatments of proven efficacy for sexual problems in female diabetes patients other than the use of lubricants during intercourse. It is most important to be able to talk about the problem in an open atmosphere. This can also be accomplished with the help of friends or women's organisations (176).
9. DIABETES EDUCATION
Optimal diabetes treatment begins with lifestyle adjustments. The patient plays an important role in this aspect of the treatment. Every day he or she is obliged to make large and small decisions that will have an influence on his or her condition. Striving for a healthy lifestyle will become a life-long concern for the patient. Education to achieve optimal self-care is therefore an important component of diabetic care (177).
The objective of self-care education is to teach patients how to manage their disease in an independent and self-reliant way (empowerment). Provided with correct information, diabetes patients can make their own decisions about their day-to-day treatment, thus becoming equal partners in their care (178).
Over the short term (<6m) self-care education has a positive effect on HbA1c values and parameters related to the quality of life (179). In order to be effective over the longer term, it is important that patient education be a continuous process and not a one-time intervention (180).
Educating the patient and providing support for lifestyle changes is a gradual process that takes place in small increments over time.
The following topics should be discussed with the patient:
Psychosocial consequences of the diabetes diagnosis for the patient,
Individually customised treatment objectives,
Personal diet requirements (with a meal plan),
The role of physical activity in the treatment,
Interaction between food intake, physical activity and oral antidiabetics/insulin,
Possible lifestyle improvements: for example, the unfavourable effects of smoking and excessive alcohol consumption, safe and correct taking/administration of medication,
Administration and adjustment of insulin as necessary,
Glucose self-monitoring and the meaning of the results within the scope of potentially required action,
Recommended reaction in the event of dysregulation (both hypoglycaemia and hyperglycaemia) or illness,
Prevention and early detection of chronic complications, paying special attention to foot care,
The use of the Diabetes Passport,
Optimal use of existing health facilities,
Necessary administrative modifications to the driver's licence.
Discussing all these topics personally with the patient is impossible for the GP.
Therefore, diabetes education will involve different care providers: doctors, dieticians, nurses, podiatrists, diabetes educators, etc.
Patient organisations like the Vlaamse Diabetes Vereniging (VDV - Flemish Diabetes Association) can also play an important role in patient education (see below). Patient education appears to be most successful when it is imparted in a coordinated manner by the different care providers (shared care). This issue is discussed in greater detail in the section on care organisation.
Furthering and hindering factors
There is often prejudice or misconception regarding both the disease and its treatment, which can only be removed by means of proper understanding of the condition.
The individual belief in the possibility of self-care and the influence each person can have on his or her own health vary from patient to patient. Emotional factors (denial, anger, guilt, depression, acceptance) can significantly influence the education process. The more drastic the changes in lifestyle and the more complex the therapy conditions, the more difficult it is to attain the treatment goal. The greater the openness and respect in the relationship between the patient and the care provider, the greater the chances of success. Communication is essential to attain success. In that situation, listening is as important as talking.
Successful diabetes education requires the following elements:
It is often important to take the patient's current situation as a point of departure,
Things that are already being done right must first be consolidated and encouraged,
The changes require the patient's consent,
Whenever it is advised not to do something, alternatives should be provided whenever possible,
It is important to use simple language and provide visual aids,
Guidelines should always be very simple and concrete,
It is necessary to verify whether the patient has understood the recommendations,
A written summary is often recommended as an aide mémoire for the patient,
It is useful to involve the patient's entourage (partner, family, colleagues).
Repetition is important.
10. SELF-MONITORING
Just as with any other chronic disease, it is also recommended to involve the diabetes patient as much as possible in monitoring his disease. The patient can manage a number of issues independently: recording weight and physical activity, self-measurement of blood pressure and glucose values are some examples. The patient must be given the appropriate self-management information and its practical feasibility must be individually evaluated.
10. 1. Glucose Self-Monitoring
Glucose self-monitoring is recommended for all Type 1 diabetes patients as it is essential for their treatment (181). Type 1 patients are much more exposed to large fluctuations in the blood glucose level and are also at greater risk of hypoglycaemia.
There is some controversy surrounding the use of glucose self-monitoring in Type 2 diabetes (182). Selective use of self-monitoring, integrated into a treatment plan with clear glycaemic objectives that meet with the patient's agreement, is certainly a sensible measure (183). Glucose self-monitoring can provide people with Type 2 diabetes with greater insight into their condition, thus contributing to the correct decisions for living with diabetes (empowerment) (184).
The stability of the patient's glycaemic control and the risk of hypoglycaemia must be taken into account in deciding whether to employ glucose self-monitoring.
Stable patients
In stable patients not being treated with medication, or else with medication involving little risk of hypoglycaemia (metformin or glitazones) glucose self-monitoring is of only limited usefulness.
In stable patients taking oral antidiabetics capable of causing hypoglycaemia (sulfonylureas, glinides) self-monitoring can be useful in people with active, irregular schedule lifestyles, or for safety reasons (professional drivers, overhead workers).
Patients taking insulin require ongoing self-monitoring, but in contrast to Type 1 diabetes, it is not generally necessary to measure glucose four times a day. In any event, Type 2 diabetes involves a lesser risk of acute hypoglycaemia or hyperglycaemia. As soon as patients require two or more insulin injections, they can be included in the Diabetes Convention, which means that test supplies are made available to them (cf. Section 6).
Unstable patients
In unstable patients on medication capable of causing hypoglycaemia or in whom the HbA1c goals cannot be reached, self-monitoring can be useful in order to adjust the therapy. We advise that in such cases a few all-day curves should be recorded in order to be used in adjusting the treatment (185).
In starting one evening injection of insulin in patients who continue to take oral antidiabetics during the day, as a rule usually three fasting glucose tests per week are sufficient in order to titre the insulin dose. After 2 to 3 weeks it is best to develop a complete all-day glucose curve in order to adjust the oral antidiabetic dose. In increasing the evening insulin dose, it is often necessary to reduce the morning and noon dose of sulfonylureas or glinides.
In acute dysregulation due to an intercurrent disease or the use of corticoids, temporary glucose self-monitoring (a few all-day curves) can help adjust the treatment.
10. 2. Self-monitoring techniques
Self-monitoring requires good education and support, not only as concerns its technical aspects, but also in regard to the interpretation of the data obtained. At first, it is possible to use a home nurse until the patient is able to perform the measurements on his/her own. Some patients will require permanent help from a home nurse or a family member.
The results of the blood tests are best recorded in a diary brought to each contact with (diabetes) care providers by the patient. In this diary the patient can record ancillary information on diet, exercise, etc.
10. 2. 1. Quality control for measuring techniques
Inaccurate measurements can occur either due to defects in the measuring device or in the test strips, or due to faulty measuring techniques. The more recent measuring devices are considerably more reliable than the older glucose meters (186).
The treating physician or diabetes nurse should carry out a quality control of the glucose self-monitoring procedure at least every six to twelve months (187).
10. 2. 2. Acceptance
Some patients still experience some inhibitions in carrying out self-monitoring. These inhibitions express themselves as shame about having to prick themselves in the presence of others, or having to prick themselves at different times and in different situations, being anxious about pricking themselves or not being able to operate the meter, and therefore being dependent on others. GPs can help their patients to put these feelings into words and thus help prevent the diabetes self-monitoring taboo.
Pricking their fingertips can also put some patients off. For this reason it is recommended always to use a pricking device and to prick the side of the finger to cause less pain. There are also meters that make it possible to prick in different alternative areas (188).
10. 3. Availability of self-monitoring supplies
Self-monitoring supplies are easy to get at the first-line treatment level, but reimbursement is not consistent. Pharmacists can propose a wide range of glucose meters and the corresponding strips. Supplies can also be obtained directly from the manufacturers and (local chapters of) patient associations. In view of the smaller profit margin applied, the latter option usually represents a less expensive solution.
Some private (mutual) health insurance schemes provide for limited reimbursement of self-monitoring supplies, whether or not within the scope of supplementary insurance. These regulations, which are different in the different insurance schemes, can also widely differ on a regional basis, so that no global information can be reported on this subject.
11. ORGANISING THE CLINICAL FOLLOW-UP
We recommend using a clearly organised paper or electronic file for proper patient follow-up. This will make it possible quickly to see what tests and examinations were recently carried out and which need to be planned.
Patients with a global medical file (Dutch acronym: GMD) can be recalled by the GP to perform certain examinations and tests in a timely manner. Such recalls can contribute to a better quality of diabetes care (189).
11. 1. The Diabetes Passport
Since 1 March 2003 Belgium has had a Diabetes Passport (190). By means of the diabetes passport, patients are encouraged to seek the advice of their GP (191). The patient's basic treatment does not require sophisticated interventions, as it could rather be qualified as "low-tech", and includes
- Careful anamnesis with targeted advice,
- Regular monitoring of
- Weight
- Blood pressure
- Pulse
- Foot examination using a monofilament
- and some biochemical parameters
- Glycaemia
- HbA1c
- Lipids (total cholesterol, HDL, LDL, triglycerides)
- Serum creatinine
- Microalbuminuria.
- ...
- and an annual eye examination (to be performed by an ophthalmologist)
This enables virtually complete follow-up of diabetes. The data will make it possible to manage glucose regulation, develop an approach to cardiovascular risk factors and detect and treat chronic diabetes complications at an early stage.
Diabetes Passport
Although the use of the Diabetes Passport has been recommended on an ongoing basis, its introduction in Belgium faced a number of difficulties. A poor promotion campaign, a shaky start-up phase and the absence of a support infrastructure created significant resistance among care providers.
In other countries, too, the efforts to optimise diabetes care and to help patients be more self-reliant by means of the use of a Diabetes Passport have met with varying levels of success (192).
11. 2. Agreeing on treatment objectives
The patient needs to overcome a certain level of resistance in order to be able to follow the proposed care regimen. There is a risk that the patient may ultimately "drop out" and limit his or her care to the resolution of acute problems without thinking of the longer-term risks.
Setting objectives is a useful aid in accomplishing them. Although the literature is convincing as concerns the fact that strict blood glucose, blood pressure, lipid control etc. guarantee the best results, not every patient is best served by such a strict regimen (193). An ideal therapy is often not achievable. In such cases it is better to work with realistic objectives that can be adapted to each patient's needs (194). Joint discussion of what may be achievable takes time, but results in greater satisfaction and better results. This approach also helps limit frustration as regards what cannot be accomplished, both for the patient and the doctor.
The following principles should be applied in determining treatment goals:
Treatment goals must be individually adapted to each patient. In doing so, scientific data, life prognosis, feasibility (the possibility for each patient to engage in and follow a specific therapy) and treatment risks (especially hypoglycaemia) should be taken into account (195);
Treatment goals should be determined jointly with the patients and must be fully understood by him/her;
The treatment goals should also be communicated to the other team members.
11. 3. Treatment compliance
In order to limit the risk of developing complications, diabetes patients are advised to take a number of different medicines and to comply with a tight monitoring and follow-up schedule. These issues of treatment compliance in regard to medication and recommendations are often not taken into consideration while no problems are experienced.
The research into factors influencing therapy compliance is rather sparse. As opposed to dozens and dozens of RCTs on individual drugs and treatments, there are only a few comparable trials investigating the problem of treatment compliance. Although difficult to evaluate, treatment compliance failure is estimated at 30 to 50 % of all patients, independently of the type of disease, the prognosis or the setting (196).
Poor treatment compliance is also considered to be the culprit in significant financial losses, which in the US are estimated at an annual cost of 100 billion US dollars, which include 10% of hospital admissions and 23% of referrals to rest and nursing homes (197).
A recent comprehensive literature study (198) reviews thirty years of research on treatment compliance. The most important issues concern the definition and measurement of treatment compliance. Furthermore, this study also examines in depth the causes of poor treatment compliance and options for improvement (199).
To date there seems to be no evidence to prove that any one method has a more positive effect on treatment compliance than another. A supportive and non-judgmental approach, as well as an exploration of what is achievable with each individual patient seems to promote treatment compliance (200). This suggests that a selective range of treatment compliance promoting strategies is necessary in order to be able to make appropriate choices for each patient and therapy. Training patients and doctors in communication skills can be a cost-effective way to increase treatment compliance and improve overall patient health.
The doctor-patient relationship
Exploring the patient's own ideas and expectations in connection with illness and health is fairly new in treatment compliance research (201). The doctor's attitude towards the patient and his or her ability to discover and respect the patient's concerns, to make easily comprehensible information available to the patient and to react empathetically are extremely important.
Studies on the relationship between communication and outcomes have demonstrated that there is a correlation between the quality of clinical communication and health outcomes (202). Agreement between doctor and patient in the analysis of the nature and significance of a clinical problem leads to an improvement and the solution of the problem. Increased patient participation in the contact improves satisfaction, treatment compliance and therapy outcomes.
For this reason it can be very useful to fathom out the patient's own perception of his or her disease and the associated feelings and expectations, to learn active and sympathetic listening methods, provide clearer explanations, evaluate the patient's conceptions or apprehensions, negotiate a treatment plan and test the patient's intentions actually to comply with it. All these (new) skills can be acquired or improved with training.
12. Approach to Type 2 diabetes patient care
As is the case in most neighbouring countries, Type 2 diabetes patients are primarily managed with first-line care, while second-line care is normally used for Type 1 patients. The differentiation between first and second-line care should not be seen as a strict dividing line, to the extent that management of both Type 1 and Type 2 patients will require joint consideration and cooperation between the different disciplines. Over the last few years there has been ever more frequent demand for a properly functioning "shared care" model with coordination of care for Type 1 patients in the second line, and in the first line for Type 2 patients.
12. 1. The diabetes team in second-line care
Rehabilitation agreement concerning self-monitoring for diabetes mellitus patients: the "Convention".
In 1988 a system was set up in Belgium to help diabetes patients be followed in a structured manner to achieve maximum self-care. This involved agreements between the authority (RIZIV) that finances the system, and the hospitals that need to comply with certain requirements.
The purpose of the agreement is to offer a self-monitoring programme to selected diabetes patients, with conditional reimbursement from the RIZIV.
All diabetes patients treated on an outpatient basis and requiring at least two insulin administrations per day are eligible for the programme. An additional condition is that these patients should be able to and willing to learn how to adjust their treatment themselves on the basis of, among other information, self-monitored glucose values, and actually do so (203).
A rehabilitation programme must fulfil at least the following aspects:
It is individually defined
It mandatorily involves the four essential aspects of diabetes treatment: insulin therapy, education, diet and exercise
It mandatorily integrates the following medical prevention measures:
Annual fundus examination by an ophthalmologist
Annual kidney function check-up with detection of microalbuminuria
Annual clinical examination for peripheral neuropathy
Annual clinical foot examination
It fits into an overall cardiovascular prevention programme managed by the treating physicians, including the GP. Special attention is paid to weight, blood pressure, lipids and smoking habits.
The rehabilitation plan (204) must at least describe in greater detail the special strengths of the rehabilitation programme, the members of the rehabilitation team (by name) and the special conditions under which a diabetes patient can be accepted into rehabilitation, including his or her input or contribution and what he or she can expect from the rehabilitation agreement. The role of the GP in the rehabilitation to self-monitoring and the other aspects of diabetes treatment must be described in greater detail, as well as what the GP can expect from the hospitals in charge of rehabilitation.
To follow a prescribed rehabilitation programme, the diabetes patient must confirm his commitment in writing to do so, including compliance with a minimum number of glucose measurements. The diabetes team makes the patient aware of the importance of his/her own contribution/input in achieving the targeted goal and of the cooperation between the various care providers, primarily the GP but also the pharmacist. The medical prescription attached to the application must be signed by a diabetologist. This prescription comprises the specific education programme and the indications. Reimbursement is possible only following approval of the Advising Physician. The application is valid for a maximum of 12 months.
Specific rehabilitation programmes are reimbursed on a monthly basis for each diabetes patient. Prices and fees depend on the patient's reimbursement bracket (205).
The programmes also require the collection of data to enable epidemiological evaluation and to further the quality of care (206).
12. 2. The diabetes team in first-line care
With properly structured cooperation, Type 2 diabetes can be entirely managed within first-line care (207). At present, the existing cooperation between care providers in not optimally structured or organised (208). However, significant efforts have been made over the last few years to improve the care provided to diabetes patients. The importance of certain disciplines in diabetes care, such as dieticians, podiatrists and reference nurses (209) has only recently been recognised. Currently, diabetes educators are only used in second-line care. How best to integrate these specially trained paramedics into first-line diabetic care is currently still under review.
12. 2. 1. Diabetology reference nurses
Nurses who teach self-care to diabetics have been reimbursed since 1 July 2003, while this had not been the case before. The new rule is part of a larger review of the home nursing nomenclature (210).
Education involves on the one hand a self-care course for new patients choosing at-home care once insulin injections have been prescribed (211) and on the other, an appropriate two-hours education programme for patients unable to self-administer the injections. They receive instruction in lifestyle rules they will need to follow (212).
The education programme is implemented by reference nurses specialised in diabetes care who, together with the home care nurse, ensure optimal diabetes care by means of a specific nursing care plan. This involves close cooperation with the patient's GP and/or diabetologist. This follow-up is not limited to "new" patients. Patients already diagnosed with the disease also qualify.
The goal is to expand this new way of working with care plans, reference nurses and self-reliance education to other chronic conditions or problems such as chronic psychiatric conditions or incontinence.
12. 2. 2. The podiatrist
A podiatrist (213) is a member of the paramedical professions who, upon referral from a doctor or specialist, examines and, if necessary, treats patients with foot complaints. Such complaints can refer to the skin or nails, but also to the motor system. To examine such patients, the podiatrist is armed with a wide range of examination techniques and clinical podiatry examinations, biomechanical measurements and gait analysis methods. The patient's functional needs are at the core of the process. The podiatrist tries to find a possible cause for the condition and, if possible, to treat it. This results not only in a short-term improvement but also drastically reduces the risk of recurrence.
Recently, the Government provided for reimbursement of podiatry services as first-line care for diabetes patients with a Diabetes Passport who are at increased risk of foot complications (Stage 2b onwards). A list of podiatrists accredited within the scope of the Diabetes Care Review Project is available on the Diabetes Passport website (214).
12. 2. 3. The Dietician
The dietician is the primary expert in the area of diet and nutrition. Dieticians/nutritionists follow a three-year higher education course (Bachelor's in Nutrition and Dietetics). Dieticians are therefore trained in professional diet consultations.
The profession of dietician was statutorily recognised in 1997 (R.O. 78 concerning the exercise of the healing arts, nursing and the paramedical professions). This Royal Order also stipulated the qualification requirements for exercising the profession and listed the technical services a doctor may delegate to a dietician.
Recently, the Government also provided for limited reimbursement of dietary counselling as part of first-line care. A list of dieticians accredited within the scope of the Diabetes Care Review Project is available on the Diabetes Passport website (215).
12. 3. Communication between care providers
We advise patients to use their Diabetes Passport to improve the communication between the individual care providers. By means of the Diabetes Passport, each individual patient's goals are shared with the other care providers. This prevents patients from getting contradictory messages from the different care providers.
The focus of care should always be on the patient. More and more frequently, it is assumed that the patient has a central place in the decision-making process. Doctors and other care providers must therefore adequately inform, care for and support the patient in making the "right" decisions.
The Diabetes Passport also represents a tool for communication with the patient. It makes it possible to agree the most realistic and achievable goals with the patient. In addition, it also enables treatment priorities to be defined by mutual agreement. Clearly, the patient's role in doing so is essential.
This approach, in which the patient is an equal partner in the care process, requires a new approach to communication on the part of the doctor (216).
12. 4. Patient associations
Vlaamse Diabetes Vereniging vzw [Flemish Diabetes Association, a non-profit organisation]
Ottergemsesteenweg 456
9000 Ghent
Tel: +32(0)9/220.05.20
Fax: +32(0)9/221.00.82
e-mail: vdv@diabetes-vdv.be
Website: www.diabetes-vdv.be
The Vlaamse Diabetes Vereniging (VDV) is an association serving the different aspects of diabetes. Its goals are:
The prevention and care of diabetes and the improvement of the quality of life of all those touched by diabetes;
Promoting the prevention of diabetes;
Furthering early diagnosis of diabetes;
Furthering prevention of complications by optimising treatment and care of diabetes patients, and by promoting self-care;
Fighting social obstacles;
The promotion of diabetes research.
The VDV had 22,500 members in 2005. The membership consists not only of diabetes patients and their entourage, but also of care providers. Its broad based membership enables the VDV to provide balanced information and to be an advocate for the needs of diabetes patients.
The VDV has a number of publications, including the bimonthly magazine Diabetes Info, which is distributed to all members. Care providers can subscribe to a monthly e-mail newsletter. The free Infoline (0800 / 96 333) answers questions asked by telephone and e-mail by people with diabetes and their entourage and by care providers. The VDV has 26 local chapters throughout Flanders, which bring the association as close as possible to people with diabetes. They organise information evenings, discussion forums and leisure activities, and make available self-care supplies at advantageous prices.
The VDV cooperates closely with the WVVH in Type 2 diabetes projects, e. g. the Flanders Diabetes Project, the Diabetes Care Review Project and the Diabetes Passport, and the present WVVH-VDV recommendation.
Social discrimination
In order to remove social discrimination against people with diabetes it is important to change the image society has of this disease (217). Most social obstacles in connection with diabetes are the consequence of preconceived opinions and an overestimation of the incidence of acute and chronic complications. Education, self-monitoring, treatment options for associated risk factors and intensive insulin therapy have helped significantly improve the outlook and prognosis of the great majority of people with diabetes.
In evaluating the risk profile, each diabetes patient must be regarded as an individual and not as a member of a group. This applies to job applications as well as to insurance contracts and requesting a driver's licence. The VDV publishes separate brochures on all the above issues.
Access to and reimbursement of diabetes care
In addition to medication, modern treatment of diabetes also requires the use of appropriate materials (such as injection material and supplies for blood glucose self-monitoring) as well as sound diabetes education (imparted by doctors, nurses, dieticians) to achieve optimal self-care.
Several services are currently not reimbursed, as they are not included in the nomenclature (diet consultation, education, etc. ). This restricts access to these treatment options for some people (e. g. the disadvantaged).
Diabetes and employment
The right to work is a fundamental human right and thus also applies to diabetes patients. Nevertheless, people with diabetes can experience difficulties in looking for, or keeping, a job. In principle, all jobs are available to people with diabetes, provided that they have the proper training and are medically eligible for it.
Diabetes cannot be a cause for discrimination on application (218). People with diabetes must be evaluated on an individual basis: the specific requirements and risks of a specific job must be weighed against the diabetic's health condition and treatment methods (diet, tablets, insulin, self-monitoring).
Diabetes and the driver's licence
It is also desirable that the evaluation of a diabetes patient's driving safety be based on individual evaluation (as opposed to being classified as a member of the "diabetes group"). For this purpose, it is best to use a standardised relevant medical condition and driving performance questionnaire. This questionnaire should be answered in part by the treating physician (219), and partially by the patient (220).
Diabetes and insurance
In subscribing to insurance policies, too, diabetes patients must be evaluated as individuals, taking into account all their risk factors. All too often, diabetics are evaluated as a group and therefore assigned a high risk score. This excludes them from certain types of insurance (e. g. hospital insurance), or forces them to pay an unjustifiably high premium surcharge (e. g. for life insurance).
It is therefore not appropriate systematically to refuse certain types of insurance to people with diabetes. This applies primarily to hospital insurance, but can also occur with insurance for a guaranteed minimum income (221).
13. CONCLUSION AND RECOMMENDATIONS
Core message Degree of evidence
Systematic screening of the entire population for Type 2 diabetes is not advised. If risk factors are present, targeted opportunistic screening (case-finding) is recommended. (cf. 2. 1) 3
In pregnancy, systematic screening for gestational diabetes is recommended, unless there are no risk factors at all. (cf. 2. 2) 2
The diagnosis of Type 2 diabetes (mellitus) is made by means of two tests performed on venous blood. We recommend using the fasting glucose value for the diagnosis. Two values >=126 mg/dl indicate diabetes. The use of an OGTT is not advisable for first-line diagnoses. (cf. 3. 1) 3
The treatment of Type 2 diabetes is based on objectives that are individually customisable and should thus be achievable for each individual patient. We advise working with a tool (the Diabetes Passport) that increases patient participation and renders the specified objectives more concrete. (cf. 4 and 12) 3
Targeted and structured education by properly trained educators increases patient self-reliance for achieving his/her own personal goals (cf. 9). 1
Obese Type 2 diabetes patients should aim for a permanent weight reduction of 5 to 10% of their body weight. (cf. 5. 2. 1) 2
In obese Type 2 diabetes patients, pharmacotherapy is started with metformin. (cf. 6. 1) 1
If treatment goals cannot be achieved with maximum oral therapy, insulin should be started without delay. (cf. 6. 2) 1
Insulin treatment requires blood glucose self-monitoring. These measurements must be carried out on an intensive basis in the run-up to and the starting phase of the insulin treatment. (cf. 6. 2) 3
Hyperglycaemia should not be undertreated due to unfounded fear of hypoglycaemia. Chronic hyperglycaemia always causes much greater morbidity and mortality in Type 2 diabetes than acute hypoglycaemia. (cf. 6) 2
Early detection and treatment of eye problems by an ophtalmologist can prevent blindness. (cf. 8. 2. 1) 2
All patients with Type 2 diabetes must receive maximum protection against cardiovascular problems. This includes: Smoking cessation counselling, blood pressure control and statin therapy. This applies all the more if microalbuminuria is found. If in doubt, a cardiovascular risk meter can clarify the usefulness of this combination therapy. (cf. 7. 1) 1
At-risk feet must be proactively and systematically detected by means of inspection, palpation and monofilament examination. Severe orthopaedic ailments and/or ulcers should be referred to a multidisciplinary foot centre without delay. (cf. 8. 2. 4) 1
The treatment of Type 2 diabetes patients requires cooperation between all care providers concerned and also with the patient. (cf. 11) 3
14. Fundamentals
Caring for people with diabetes requires systematic involvement of other, recognised (!) first-line providers: educators, (reference) nurses, dieticians, pharmacists, physiotherapists, psychologists, practice assistants.
Structural cooperation with the second (and third) line of treatment is necessary, based on equality and complementarity and supported by validated care paths in which competitive concerns have no place.
The exchange of information via the patient as conceived with the Diabetes Passport is essential in achieving this end, but is optimally accomplished in an automated manner enabling all care providers to review the patient's file.
To increase the quality of care, a local diabetes bank should be developed to provide the GPs of the region with quality feedback.
GPs and other physicians should develop the necessary communication skills to manage chronic patient care. In chronic care situations, special attention should be devoted to developing personal goals and voicing and discussing treatment compliance problems.
The GP must be structurally supported in order to be able to assume his role as care coordinator. This requires mandatory registration of all diabetes patients in a GMD [Dutch acronym for Globaal Medisch Dossier, Global Medical File] at a GP's office of their choice.
Caring for people with diabetes in general practice requires compensation that is in proportion to the duration and complexity of the care process. Such compensation should not invite short and frequent doctor/patient contacts.
Every GP should be able to access quickly and easily available (free) evidence-based information (such as recommendations, Minerva etc. ) in order to be able to perform objective management of diabetes patients.
Patients should be able to gain temporary access to a glucose meter, a prick pen and test strips whenever necessary, as well as in the event of illness or insufficient therapeutic response. Patients on insulin (even if only one injection) should be able to have permanent access to supplies.
In addition, patients should be able to get access to a limited number of test strips to perform self-monitoring over a short period of time.
15. RESEARCH AGENDA
What is the validity of current early detection criteria (case-finding) in Type 2 diabetes? How often should this type of detection be repeated?
How is ideal collaboration between GPs and other first-line workers developed in regard to diet advice? What is the ideal frequency for referral to the dietician in order to achieve the best possible outcome in Type 2 diabetes patients?
What type and frequency of physical activity counselling delivers the best outcomes in Type 2 diabetes patients?
When is it best to start oral antidiabetics, and when is it best to start insulin? What is the ideal step-by-step plan for combining therapies?
What are the ideal prerequisites for starting insulin in first-line care?
On the basis of what decision-making model can the approach to cardiovascular risk be improved in Type 2 diabetes?
How can early detection of eye problems be improved? What are the ideal referral strategies in this case? What contribution can be derived from new technical options?
What is the value of self-monitoring in the follow-up of Type 2 diabetes? How frequently should measurements take place and which parameters should ideally be used to obtain better outcomes?
How can the Diabetes Passport and the use of a clear and easily accessible medical file improve the collaboration between care providers and patients to obtain optimal outcomes?
What is the effect of shared care (clinical care paths) on the outcomes of diabetic care in Type 2 diabetes?
16. IMPLEMENTATION
This recommendation is the result of broad research that looked into the desirability of diabetes screening, the proper diagnostic procedures for Type 2 diabetes, the related goals, the wisdom of lifestyle counselling and self-care education as well as the correct type of treatment as concerns oral antidiabetics and insulin. The treatment of diabetes complications and the follow-up of cardiovascular risk factors were also discussed within the broader scope of shared care.
The point of departure was the "Consensus for the Detection and Treatment of Type 2 Diabetes Mellitus" published in 1997 as a result of a collaboration between the WVVH and the VDV.
A multidisciplinary group of authors was assembled to perform this task (Dr J. Wens, Prof. Dr P. Van Royen, Dr H. Bastiaens, Dr P. Sunaert and Dr L. Feyen (GPs) as well as Dr F. Nobels and Dr P. Van Crombrugge (endocrinologists)). They further developed and updated the scope of the study. To aid in obtaining answers to the various questions raised in the study, the relevant literature was systematically reviewed by means of the virtual library of the Cebam [Belgian Centre for Evidence-Based Medicine]. Searches targeted systematic reviews, whether or not with meta-analyses (DARE and Cochrane databases), quality recommendations (National Guideline Clearinghouse and Guidelines Finder UK) and primary literature (MedLine). The most significant keywords used throughout were the following MESH terms: diabetes mellitus, non-insulin-dependent, diabetes mellitus, Type 2. Searches concentrated on literature published after 2000. Depending on the different section headings, these search terms were combined with relevant key words. Clinical Evidence and Minerva were also used whenever relevant topics were found to be available in these sources. This resulted in a first draft entitled "Type 2 Diabetes Mellitus".
A first working text was rewritten taking into account the remarks made by the experts: GPs Dres Thierry Christiaens, Koen Cornelli, Geert De Loof, Geert Goderis, Annie Goeman, Stefan Teughels and Bouma (Nederlands Huisarts Genootschap NHG - Dutch GP Association); endocrinologists Prof. Dr Chantal Mathieu, Prof. Dr Raoul Rottiers, Dr An Verhaegen; cardiologist Prof. Dr Benoit Boland, ophthalmologist Dr E. Smets, Ms Ria Patteet (nurse / diabetes educator), Ms M. Marcipont (dietician), Mr Guy Noldus and Ms Hilde Layaye (Flemish Diabetes Association VDV), Prof. Dr Guy De Backer (public health specialist) and Prof. Dr Erik Muls (preventive health care). A mention of a contributor as being an expert does not necessarily imply that each expert subscribes to the recommendation in every detail. Then the revised text was tested in four Flemish local quality groups [LQGs] (Heppen, Mortsel, Kortrijk and Herk-de-Stad).
The final text was amended taking into account the remarks from the LQGs and was then submitted to the editors of Huisarts Nu. Following a final edit, the recommendation was ultimately submitted to the CEBAM Validation Commission. The text will be updated on an annual basis, and the recommendation will be entirely reviewed after five years. In the follow-up, the primary focus will be on whether the key messages do not require changes; this will be decided on the basis of a systematic literature search in the literature for the previous year. The same search terms will be used in this literature search as in that underlying the development of this recommendation. Only meta-analyses, systematic reviews and controlled trials will be taken into account.
The authors and the members of the Recommendations Steering Group have no connection with the pharmaceutical industry. No conflicts of interest are known to exist.
17. LEVELS OF EVIDENCE
Pronouncements and opinions in the WVVH recommendations for good medical practice are based on a level of evidence that reflects the reliability of the pronouncements:
Level 1
The requirement for Level 1 is that there should be at least two studies with equivalent results, carried out independently from each other, and falling within one of the following categories:
a good quality RCT;
a good quality independent blind comparison of a diagnostic test with the reference test (i. e. with a target group of consecutive patients and where both the diagnostic and the reference test were performed);
a good quality prospective cohort study with 80% or greater follow-up.
A highly consistent systematic review or meta-analysis of this type of article is also sufficient for this level of evidence.
As a conclusion for such studies we state that "it has been demonstrated that...".
Level 2
The requirement for Level 2 is that there should be at least two studies with equivalent results, carried out independently from each other, and falling within one of the following categories:
a moderate quality RCT;
a moderate quality independent blind comparison of a diagnostic test with the reference test (i. e. with a limited portion of the target group or where the reference test is not performed on each subject);
a moderate quality (retrospective) cohort study or patient monitoring study.
A highly consistent systematic review or meta-analysis of this type of article is sufficient for this level of evidence.
If there is only one study available out of those listed under Level 1, the result is a Level 2.
As a conclusion for such studies we state that "it can be assumed that..."
Level 3
An absence of good quality comparative studies results in a third level of evidence, meaning that:
there are no good quality RCTs;
there is only one moderate quality study and there are no meta-analyses of moderate quality studies;
the conclusions of the RCTs or meta-analyses are contradictory.
This level also includes the consistent opinion of at least two experts, a recommendation or conclusion arrived at after consideration of all available material and consensus within the group of authors. In all these cases we only refer to "an indication that..." - or to that "the working group is of the opinion that...''
18. DEFINITIONS
Abdominal obesity In Caucasians, abdominal obesity is reported with a waist girth >=94 cm for men and >=80 cm for women. The term "central obesity" is used as a synonym.
IGT = Impaired glucose tolerance Plasma glucose 2 hours after stressing = >=140 mg/dl and <200 mg/dl (7.8 mmol/l and 11.1 mmol/l)
Glucotoxicity The adverse effect of high glucose levels on insulin secretion and insulin sensitivity
IFG = Impaired fasting glucose Fasting plasma glucose with a value of >=100 mg/dl and <126 mg/dl (5.5 mmol/l and 7.0 mmol/l)
Hypoglycaemia An event in which the typical signs of hypoglycaemia (sweating, shivering, palpitations and also concentration and behavioural problems and changes in consciousness) are combined with a plasma glucose concentration of =70 mg/dl (3.9 mmol/l).
LADA = Latent Autoimmune Diabetes of Adults This is a special, slowly developing form of Type 1 diabetes. Diagnosis sometimes only becomes obvious because treatment started has little effect and the patient continues to complain of hyperglycaemia. In such cases, referral to a multidisciplinary diabetes team will become necessary.
Metabolic syndrome (222) Metabolic syndrome is diagnosed in the simultaneous presence of abdominal obesity and two concurrent factors out of a list of four. Abdominal obesity is defined as a waist girth >=94 cm for European men and >=80 cm for European women.
Additional factors:
Triglycerides: >=150 mg/dl (1. 7 mmol/l) or treatment therefor
HDL cholesterol <40 mg/dl (1. 0 mmol/l) or treatment therefor
Blood pressure: systolic >130 mmHg or diastolic >85 mmHg or treatment therefor
Fasting plasma glucose >100 mg/dl (5. 6 mmol/l) or Type 2 diabetes diagnosed at an earlier stage.
MIDD = Maternally Inherited Diabetes and Deafness In combinations of diabetes and deafness, genetic mitochondrial defects transmitted only through the maternal line should be taken into consideration: "Maternally Inherited Diabetes and Deafness"
MODY = Maturity-Onset Diabetes of the Young This is a relatively frequent special form of Type 2 diabetes that occurs at an early age (before age 25) and which is hereditary as an autosomal dominant characteristic. A number of genetic defects have been found to be at the origin of this condition.
FPG = Fasting Plasma Glucose
OGTT = Oral Glucose Tolerance Test Proper performance of the OGTT 100 g stress test requires an accurate procedure. The test should be carried out in the morning after 8 to 14 hours' fasting, following several days of unrestricted diet (>150 g carbohydrates per day) and unrestricted physical effort. The patient must remain seated during the test and may not smoke.
Secondary diabetes Secondary diabetes is a form of diabetes in which another disease is at the root of the development of the diabetes.
The most frequent causes of secondary diabetes are:
Diseases of the pancreas: pancreatitis (alcohol abuse), neoplasia
Metabolic conditions: hemochromatosis
Endocrine disorders: hyperthyroidism, Cushing's syndrome, acromegaly, etc.
Use of diabetogenics: diuretics, corticosteroids, nicotine acid, etc.
Stress hyperglycaemia Medical stress such as infection, trauma, surgery or use of certain drugs can result in temporarily increased glycaemia. This is called stress hyperglycaemia.
Gestational diabetes Diabetes that develops during pregnancy.
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