Peripheral rather than hepatic insulin resistance and atherogenic lipoprotein phenotype predict cardiovascular complications in IDDM

Microalbuminuria, hypertension and hyperinsulinaemia are three independent risk factors for cardiac disease in non insulin-dependent diabetes (NIDDM). However, it is unknown to what extent hyperinsulinaemia reflects resistance to insulin action at hepatic, extrahepatic or at both sites. A cross-sectional study from our Department showed that peripheral insulin resistance, hypertension, microalbuminuria and lipid abnormalities are associated in NIDDM. Non diabetic individuals with the so-called 'atherogenic lipoprotein phenotype', characterized by small dense low density lipoproteins (LDL subclass pattern B) have up to 3-fold higher risk of myocardial infarction. The aim of the present study was to investigate whether impaired peripheral insulin sensitivity, during euglycaemic-hyperinsulinaemic clamp, as well as abnormalities in lipid concentrations and LDL size, predict abnormalities in albumin excretion rate, blood pressure and cardiac function in 73 consecutive normotensive ( 0.001). The two groups displayed similar patterns of age, gender, body weight, diabetes duration, HbA(1c) and cardiac ischaemic events. During 6-year follow-up the rate of occurrence of microalbuminuria (> 20 mu g min(-1)) (7% vs. 15%, P 90 mmHg) (l4 vs. 30%, P < 0.05) was significantly higher in group 2 than in group 1 NIDDM patients. Events of cardiac ischaemic disease were more frequently found among group 2 rather than group 1 patients, during the follow-up (angina pectoris: 3/28 subjects in group 1 vs. 9/45 subjects in group 2, P < 0.05; positive resting ECG: 3/28 subjects in group 1 vs. 9/45 subjects in group 2; positive exercise ECG 4/28 in group 1 vs. 11/45 in group 2). Group 2 patients were also characterized by higher triglyceride and lower high density lipoprotein cholesterol levels and by LDL subclass pattern B. Peripheral, rather than hepatic, resistance and atherogenic lipoprotein phenotype are the clinical hallmark of NIDDM patients who are prone to develop microalbuminuria, hypertension and cardiac ischaemic diseas