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Background and Aims: We evaluated whether hyperinsulinemia and/or insulin resistance are independently associated with plasma lipids, uric acid and blood pressure in non-diabetic subjects., Methods and Results: A database of non-diabetic Italian subjects has recently been set up using data from hyperinsulinemic euglycemic clamp studies carried out using the standard technique (40 mU per min per square meter of body surface area). In this database we evaluated the relationships between fasting plasma insulin (FPI), glucose metabolized during clamp (M) and plasma levels of triglycerides (TG), high density lipoprotein cholesterol (HDL-C), uric acid (UA) as well as blood pressure (BP) in non-diabetic subjects with fasting plasma glucose <6.1 mmol/l. Parallel analyses were conducted in all subjects in the database (n=1093) and in those with all variables available (n=309). In the univariate analysis both FPI and M were significantly correlated with TG, HDL-C, UA and BP (systolic, diastolic and mean). Multivariate regression analyses including center, sex, age, body mass index (BMI), FPI and M as independent variables showed that: (1) TG and UA were positively correlated with FPI and negatively correlated with M; (2) HDL-C was negatively correlated with FPI and positively correlated with M; and (3) BP was negatively correlated with both FPI and M. Analyses of covariance showed that, after adjusting for center, sex, age and BMI, subjects with isolated hyperinsulinemia or isolated insulin resistance had higher TG and UA and lower HDL-C. Subjects with isolated insulin resistance had also higher BP whereas subjects with isolated hyperinsulinemia had lower BP. Subjects with both defects had a worse profile., Conclusions: Hyperinsulinemia and insulin resistance might contribute with distinct and independent mechanisms to the development of several metabolic and hemodynamic disorders often clustering in the same individual. In particular, hypertriglyceridemia, low HDL-cholesterol and hyperuricemia seem to be related to both hyperinsulinemia and insulin resistance, whereas hypertension seems to be related only to insulin resistance.

Upregulation of endothelial adhesion molecules is the earliest step of atherogenesis. Whether obesity induces endothelial adhesin upregulation is unknown. To address this topic, circulating vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), E-selectin, and von Willebrand factor (vWF) concentrations were evaluated in 22 obese hypertensive (51.4+/-4.6 years [mean+/-SD age]), 19 obese normotensive (50.6+/-3.8 years), 18 nonobese hypertensive (52.3+/-3.9 years), and 16 nonobese normotensive (52. 4+/-3.5 years) men without other risk factors or overt atherosclerosis. All measurements were repeated in the obese subgroups after weight loss induced by 12 weeks of caloric restriction. Basal circulating VCAM-1 levels were similar between the 2 obese groups but were higher (P<0.0001) than in the 2 nonobese groups. No differences were found between nonobese hypertensives and normotensives. Serum low density lipoprotein cholesterol was weakly correlated with plasma soluble VCAM-1 levels in pooled, obese subjects (r=0.362, P=0.02). Plasma soluble adhesin and vWF concentrations decreased significantly after weight loss in obese hypertensives (VCAM-1 P=0.03, ICAM-1 P=0.004, E-selectin P<0.0001, and vWF P=0.003) and normotensives (VCAM-1 P=0.04, ICAM-1 P=0.003, E-selectin P<0.0001, and vWF P<0.0001). Body mass index was correlated with plasma E-selectin concentrations at baseline and after weight loss in obese hypertensives (r=0.501, P=0.018 and r=0. 466, P=0.03, respectively) and obese normotensives (r=0.523, P=0.021 and r=0.460, P=0.05, respectively). In conclusion, our data show that obesity per se induces early endothelial activation in hypertensive and normotensive men. Weight loss counteracted endothelial activation in both obese hypertensive and normotensive men.

The 24 h periodic pattern of blood pressure was studied in 44 patients with diabetes mellitus (14 type 1, 30 type 2; mean duration of disease 6.5 +/- 1.8 years) in good metabolic control but with abnormal cardiovascular reflex responses; of these 21 were normotensive and 23 hypertensive. All had abnormal responses to at least two out of four tests: deep breathing, lying to standing, Valsalva manoeuvre and postural hypotension. Two sex- and age-matched groups, consisting of 20 normotensive and 20 hypertensive diabetic patients without dysautonomia, were studied as controls. Each patient underwent ambulatory blood pressure monitoring for at least 24 h, using an auscultatory automatic device. Data were analysed using the sum of three periodic functions (Fourier partial sum). In the diabetic normotensive groups, the absolute blood pressure fell to its night-time minimum more rapidly, and increased to its morning maximum more slowly, in those with abnormal cardiovascular reflexes than in the controls (nightly blood pressure decrease -5.8/-4.7 vs. -3.8/-4.0 mmHg/h; increase 4.7/3.6 vs. 5.9/6.1 mmHg/h). The same behaviour was found in both hypertensive groups but the amplitude of the differences was more marked (blood pressure nocturnal decrease -7.7/-7.1 vs. -4.3/-3.9 mmHg/h; increase 3.2/2.1 vs. 5.8/4.3 mmHg/h). This analysis of 24 h ambulatory blood pressure data may be of value in diagnosis and evaluation of autonomic deficits.

The aim of our study was to analyse the 24-h periodic pattern of blood pressure (BP) in diabetic patients with abnormal responses to cardiovascular reflexes, in order to evaluate the extent of the initial autonomic damage. We studied 44 patients with diabetes mellitus (14 insulin-dependent, 30 non-insulin-dependent; mean duration of disease 6.5 +/- 1.8 years) in good metabolic control (fasting glycaemia less than 140 mg/dl, postprandial glycaemia less than 180 mg/dl, fructosamine less than 285 mg/dl), divided into two subgroups, containing 21 normotensives (13 males and 8 females aged 28-72 years) and 23 hypertensives (13 males and 10 females aged 32-70 years) respectively. All patients showed abnormal responses to at least two out of four tests: deep breathing, lying to standing, Valsalva manoeuvre and postural hypotension. Two sex- and age-matched control groups were recruited, comprising 20 normotensive and 20 hypertensive diabetic patients without dysautonomia, respectively. The reference group consisted of 248 normotensives (135 males and 113 females, aged 18-76 years) and 212 mild-moderate hypertensives (130 males and 82 females, aged 27-66 years). Each patient underwent ambulatory BP monitoring for at least 24 h, using an auscultatory automatic device. Data concerning biological rhythms were analysed by means of periodic functions. We limited the Fourier partial sums to the first three harmonics.(ABSTRACT TRUNCATED AT 250 WORDS)

In elderly patients diabetes and hypertension play an important and synergistic role in the development of cardiovascular complications. For this reason therapy must reduce blood pressure without compromising blood glucose control. We investigated the question of whether captopril, an angiotensin converting enzyme inhibitor, can be used without interference to glucose metabolism in diabetics with secondary failure. Ten elderly hypertensive diabetics (diastolic blood pressure greater than 95 mmHg), maintained in good metabolic control using oral hypoglycaemic agents and insulin, were studied before and after 30 days of captopril at 100 mg/day. We measured the following parameters: blood pressure, heart rate, fructosamine and a daily profile for blood glucose and c-peptide. There was a statistically significant reduction in systolic and diastolic blood pressure. No difference was observed in the levels of blood glucose and fructosamine. Insulin secretion as determined by c-peptide levels was not modified, in contrast with findings reported for the use of beta-blockers, diuretics or nifedipine. It seems that captopril is useful and without side effects, even in secondary-failure diabetic patients characterized by unstable metabolic control.

The aim of this study is to contribute to the understanding of the probable role of the renin-angiotensin-aldosterone, the kallikrein-kinins and the prostaglandins systems on the various types of essential hypertension and also their contribution to the action of captopril. Nineteen patients, 7 with high and 12 with normal or low levels of plasma renin activity (PRA), have been studied. Captopril (100 mg) was administered in acute dosage, blood pressure was checked for two hours and PRA and plasma aldosterone were assayed. The same trial was repeated after inhibition of prostaglandin-synthetase with indomethacin and kallikrein with trasylol, alternatively, and then with indomethacin and trasylol, contemporaneously. Our results showed that the renal vasodilative system was probably also involved in the mechanism of action of captopril, but that this drug reduced blood pressure mainly through a block of angiotensin II production in both groups of patients. Thus the finding of a normal or low PRA does not justify the conclusion that angiotensin II is not one of the mechanisms responsible for an elevated arterial pressure.