A proposed rationale for the selection of drugs in the treatment of type 2 diabetes mellitus is given in Figure 1.3.
Metabolic Syndrome
The outstanding significance of treating the metabolic syndrome to prevent type 2 diabetes mellitus has already been discussed. The metabolic syndrome usually persists in clinical type 2 diabetes, and therefore its treatment remains important.
The impact of overweight/obesity and the importance of weight reduction have been repeatedly confirmed. Weight reduction is not easy. Even more difficult is maintaining reduced body weight over long periods of time. The ideal aim is normal body weight, which will very seldom be achieved. However, much lesser weight reduction is also beneficial [53,54,62,336]. In support of nonpharmacological treatment with nutrition and physical activity, two drugs have recently been introduced: the intestinal lipase inhibitor orlistat, which reduces nutritional fat absorption, and the serotonin/norepinephrine reuptake inhibitor sibutramine, which is an appetite suppressant. Both drugs have been shown to enhance weight loss during conventional weight reduction programs. Orlistat may inhibit absorption not only of fat but also of lipid-soluble drugs and essential nutrients. Sibutramine may evoke psycho-neurological symptoms and increase arterial blood pressure. The drug also has the drawback of a variety of contraindications and drug interactions.
The beneficial effect of lowering elevated blood pressure and specific drug effects on nephropathy and coronary artery disease have already been discussed. The UKPDS [158] has shown that lowering blood pressure from 154/87 to 144/82 mmHg significantly reduced diabetes-related endpoints by 24%, microvascular endpoints by 37%, and stroke by 44%. The epidemiological analysis of this study offers the conclusion that the lowest risk will be “in those with systolic blood pressure less than 120 mm Hg” [159].
Dyslipoproteinemia that does not respond to weight reduction should be corrected by pharmacological therapy. Statins are the first-choice drug if serum cholesterol is elevated. They have favorable effects on small, dense LDL and lower the risk of macroangiopathy complications [429,430]. Fibrates (and analogues) should be favored if triglycerides are increased. These drugs also lower plasma fibrinogen and are beneficial for hypercoagulation and impaired microcirculation. However, the combination of statins and fibrates (and analogues) should definitely be avoided, because it increases the risk of myositis and other severe adverse drug effects.
Prophylactic treatment of hypercoagulation with aspirin or other drugs that reduce platelet aggregation has been recommended [228,304].
Treatment of the metabolic syndrome requires lifestyle changes. Physical activity should be integrated into everyday life, and every smoker should be offered a course in giving up smoking.
This kind of broad approach has been proven to be effective both in preventing [337,338] and in managing [431] type 2diabetes mellitus. The task for the future will be to integrate this experience into public health.
References
[1] National Diabetes Data Group. Classification and diagnosis of diabetes mellitus and other categories of glucose intolerance. Diabetes 1979; 28: 1039-57.
[2] World Health Organization. Diabetes mellitus: Report of a WHO Study Group. Geneva: World Health Organization; 1985.
[3] American Diabetes Association. Report of the Expert Committee on Diagnosis and Classification of Diabetes Mellitus. Diabetes Care 1998; 21 (suppl 1): S5-19.
[4] The DECODE Study Group on behalf of the European Diabetes Epidemiology Group. Consequences of the new criteria for diabetes in older men and women-the DECODE study (Diabetes epidemiology: Collaborative analysis of diagnostic criteria in Europe). Diabetes Care 1999; 22: 1667-71.
[5] The DECODE Study Group on behalf of the European Diabetes Epidemiology Group. Glucose tolerance and cardiovascular mortality: comparison of fasting and 2-hour diagnostic criteria. Arch Intern Med 2001; 161: 397-404.
[6] Rathmann W, Giani G, Mielck A. Cardiovascular risk factors in newly diagnosed abnormal glucose tolerance: comparison of 1997 ADA and 1985 WHO criteria. Diabetologia 1999; 42: 1268-9.
[7] Tominaga M, Eguchi H, Manaka H, Igarashi K, Kato T, Sekikawa A. Impaired glucose tolerance is a risk factor for cardiovascular disease, but not impaired fasting glucose. Diabetes Care 1999; 22: 920-4.
[8] Balkau B. The Decode study: Diabetes epidemiology: collaborative analysis of diagnostic criteria in Europe. Diabetes Metab (Paris) 2000; 26: 282-6.
[9] Ekoe JM. Epidemiology and etiopathogenesis of IDDM in other ethnic groups. In: Alberti KGMM. DeFronzo RA, Keen H, Zimmet P, editors. International textbook of diabetes mellitus. Chichester: John Wiley and Sons Ltd: 1992:129-45.
[10] Green A, Gale EAM, Patterson CC, for the EURODIAB ACE Study Group. Incidence of childhood-onset insulin-dependent diabetes mellitus: The EURODIAB ACE Study. Lancet 1992; 339: 905-9.
[11] Karvonen M, Tuomilehto J, Libman I, La Porte R, for the World Health Organization DIAMOND Project Group. A review of the recent epidemiological data on the worldwide incidence of type 1 (insulin-dependent) diabetes mellitus. Diabetologia 1993; 36: 883-92.
[12] Schiel R, Mueller UA. GAD autoantibodies in a selection-free population of insulin treated diabetic patients: indicator of a high prevalence of LADA? Diab Res Clin Pract 2000; 49: 33-40.
[13] Neu A, Kehrer M, Hub R, Ranke MB. Incidence of diabetes in German children aged 0-14 years. Diabetes Care 1997; 20: 530-3.
[14] Onkamo P, Väänänen S, Karvonen M, Tuomilehto J. Worldwide increase in incidence of type 1 diabetes–the analysis of the data on published incidence trends. Diabetologia 1999; 42: 1395-403.
[15] Rosenbauer J, Herzig P, Kries R von, Neu A, Giani G. Temporal, seasonal and geographical incidence patterns of type 1 diabetes mellitus in children under 5 years of age In Germany. Diabetologia 1999; 42: 1055-9.
[16] Karvonen M, Pitkäniemi J, Tuomilehto J, the Finnish Childhood Diabetes Registry Group. The onset age of type 1 diabetes in Finnish children has become younger. Diab Care 1999; 22: 1066-70.
[17] Bingley PJ, Douek JF, Rogers CA, Gale EAM, on behalf of the BOX (Bart's-Oxford) Study Group. Influence of maternal age at delivery and birth order on the risk of type 1 diabetes in childhood: prospective population based family study. BMJ 2000; 321:420-4.
[18] Deckert T, Poulsen JE, Larsen M. Prognosis of diabetics with diabetes onset before the age of thirty one, I: Survival, causes of death, and complications. Diabetologia 1978; 14: 363-70.
[19] Rossing P, Hougaard P, Borch-Johnsen K, Parving HH. Predictors of mortality in insulin dependent diabetes: 10 year observational follow-up study. BMJ 1996; 313: 779-84.
[20] Borch-Johnsen K, Kreiner S, Deckert T. Mortality of type 1 (insulin-dependent) diabetes mellitus in Denmark: a study of relative mortality in 2930 Danish type 1 diabetic patients diagnosed from 1933-1972. Diabetologia 1986; 29:767-72.
[21]