Insulin resistance (IR) is considered to be an important factor influencing the progression of atherosclerosis and is associated with higher morbidity and mortality. IR is a common feature of diabetes mellitus Type 2 and obesity. Many authors consider IR being the crucial abnormality of the metabolic syndrome which is characterized by the essential hypertension, hyperliproteinemia, visceral obesity, endothel dysfunction and many other abnormalities. Impaired insulin action (IR) is also described in diabetes mellitus Type 1, however this phenomenon has not been fully explained. The subjects of dissertation thesis was directed on the IR importance in diabetic Type 1 patients as well as on the renin angiotensin system inhibition in patients with IR and metabolic syndrome with impaired glucose homeostasis. Hyperinsulinemic euglycemic clamp is used in combination with indirect calorimetry to estimate the IR in vivo in humans. In our project we focused on a) the existence of the metabolic inflexibility phenomenon in type 1 diabetic patients b) the methodological evaluation of the hyperinsulinemic euglycemic clamp procedure in the same group c) the influence of renin angiotensin system inhibition with angiotensin II type 1 receptor inhibitor telmisartan in patients with metabolic syndrome and impaired glucose...

Background: Diabetes mellitus is a chronic disease that manifests as an increased level of glucose in the blood. According to the World Health Organization (WHO), 347 million people have diabetes worldwide. In year 2004, 3.4 million people died from the consequences of high blood glucose. In the Swedish population the prevalence of diabetes is estimated to 3-4 %, out of which 85-90% are Type 2. Among senior citizens a prevalence of diabetes is seen in Sweden up to 14 - 15%. Diabetes is increasing globally, particularly in developing countries, which is probably a consequence of the increased prevalence of overweight and obesity combined with low physical activity. Angiotensin converting enzyme (ACE) inhibitors are the first-line therapy in the treatment of high blood pressure among diabetics and patients suffering from congestive heart failure. The action of these inhibitors results in a decreased formation of angiotensin 2, an endogenous hormone peptide that raises the blood pressure by contracting the blood vessels. ACE inhibitors are also beneficial in the treatment of patients with renal insufficiency.Objective: The aim of this project was, with the help of published clinical trials and meta-analysis, to examine the effect of ACE inhibitors on cardiovascular diseases and mortality in type 2 diabetic and diabetic in hypertensive patients.Results: Appraisals of clinical trials within the frame of this project revealed thatACE inhibitor in patients with diabetes reduces:- Myocardial infarction (NNT = 37 during 4.5 years),- Development of stroke (NNT = 32 during 2.8 years),- Cardiovascular events (NNT = 29 during 4.5 years),- Total mortality (NNT = 20 during 2.8 years).- Left ventricular dysfunction (NNT = 6 during 3.4 years)- Complications that usually occur in association with diabetes such as nephropathy (NNT = 83 during 5 years).Conclusion: ACE inhibitors are considered well-established and safe drugs. Despite that, only 38% of the patients with diabetic in Sweden are prescribed ACE inhibitors or angiotensin II antagonists. Due to the high efficacy of ACE-inhibitors among patients with diabetes (i.e. treating 15 high-risk diabetic patients with ACE-inhibitors for a median of 4.5 years prevents one incidence of myocardial infarction, stroke, or cardiovascular mortality) measures ought to be taken in favour of a more widespread use of ACE-inhibitors among patients with diabetes. This will result not only in medical benefits, but also in reducing cost of caring for the elderly diabetics in the community. For most diabetic patients it is very cost effective to prescribe an ACE-inhibitor therapy.

Insulin resistance (IR) is considered to be an important factor influencing the progression of atherosclerosis and is associated with higher morbidity and mortality. IR is a common feature of diabetes mellitus Type 2 and obesity. Many authors consider IR being the crucial abnormality of the metabolic syndrome which is characterized by the essential hypertension, hyperliproteinemia, visceral obesity, endothel dysfunction and many other abnormalities. Impaired insulin action (IR) is also described in diabetes mellitus Type 1, however this phenomenon has not been fully explained. The subjects of dissertation thesis was directed on the IR importance in diabetic Type 1 patients as well as on the renin angiotensin system inhibition in patients with IR and metabolic syndrome with impaired glucose homeostasis. Hyperinsulinemic euglycemic clamp is used in combination with indirect calorimetry to estimate the IR in vivo in humans. In our project we focused on a) the existence of the metabolic inflexibility phenomenon in type 1 diabetic patients b) the methodological evaluation of the hyperinsulinemic euglycemic clamp procedure in the same group c) the influence of renin angiotensin system inhibition with angiotensin II type 1 receptor inhibitor telmisartan in patients with metabolic syndrome and impaired glucose...