No abstract

In order to gain insight into the potential role of endothelin, a 21 amino acid peptide produced by endothelial cells, in the development of complications of diabetes mellitus, basal plasma endothelin levels were measured in 152 patients with diabetes mellitus (83 patients with type 1 diabetes mellitus, 69 patients with type 2 diabetes mellitus) and compared to those in 50 healthy controls. Blood was drawn at 8:00 AM under resting conditions and endothelin was measured after prior extraction by a sensitive radioimmunoassay specific for both endothelin 1 and 2. Endothelin levels were increased in patients with diabetes mellitus in comparison to controls. In type 1 diabetes mellitus a positive correlation between endothelin levels and age was found. We found that 60% of patients with type 1 diabetes mellitus and elevated endothelin levels higher than 2.5 pg/mL (highest value in a control person) had had diabetes for more than 20 years (P less than .05 v patients with normal endothelin levels). In type 2 diabetes mellitus the relation between elevated endothelin levels and diabetes duration was reversed. Glycosylated hemoglobin (HbA1) concentrations above 10% of total hemoglobin were measured in 62% of the patients. Arterial hypertension was present in 60% of the patients with type 1 diabetes mellitus and increased endothelin levels greater than 2.5 pg/mL (both P less than .05 v patients with normal endothelin levels).(ABSTRACT TRUNCATED AT 250 WORDS)

We determined lipoproteins, apolipoproteins, and endothelin in 98 patients (58 female and 40 male, age 18-72 years) with hyperlipidemia (plasma cholesterol > 2.5 g/l and/or triglycerides > 2.0 g/l) and in 50 healthy subjects (20 female, 30 male, age 19-68 years). In patients with hyperlipidemia endothelin levels were elevated compared to healthy controls. Patients with plasma cholesterol above 2.5 g/l had higher endothelin and lipoprotein(a) concentrations than patients with plasma cholesterol levels less than 2.5 g/l. A positive correlation was found between the concentrations of endothelin and apolipoprotein B (r = 0.2137; P < 0.013). Smoking patients with lipoprotein (a) above 300 mg/l had higher endothelin levels than both nonsmoking patients with lipoprotein (a) above 300 mg/l and smokers with normal lipoprotein(a). In smokers endothelin correlated positively with Lp(a) (r = 0.709; P < 0.01). No correlation was found between endothelin and triglycerides nor between endothelin and age or sex. The results suggest that the vasoconstrictor endothelin contributes to the increased vasal tone in hyperlipidemia. Because endothelin also has mitogenic properties, it may play a relevant role in the development of premature atherosclerosis in patients with hyperlipidemia.

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Potential impairment of the efficacy of human atrial natriuretic peptide (human ANF-(99-126), hANP), the most potent endogenous natriuretic agent in healthy subjects, was examined in eight male normotensive patients with uncomplicated type 1 diabetes mellitus (aged 22-37 years). After giving informed consent, patients and eight male control subjects (aged 22-28 years) received in a random double-blind study design i.v. bolus injections of 100 micrograms hANP (Bissendorf peptide) or placebo. At base-line, patients differed from controls in elevated creatinine clearance (P less than 0.05) and in mild postprandial hyperglycemia. Whereas the responses of urinary cyclic guanosine monophosphate, the second messenger of hANP, were found to be normal in patients, the diuretic and natriuretic effects of hANP were grossly impaired when compared to controls (P less than 0.01); hANP resulted in increased plasma protein concentrations only in controls (P less than 0.05 vs patients). In both groups, creatinine clearance remained uninfluenced by hANP. There were similar decreases in plasma renin activity, aldosterone, levels, and blood pressure (systolic more than diastolic) in both groups (P less than 0.05 vs placebo). Heart rate and blood glucose remained unchanged. Thus, there is evidence for a decreased responsiveness to hANP exclusively of renal fluid, sodium, and chloride excretion in uncomplicated type 1 diabetes mellitus. The mechanisms responsible for this phenomenon remain obscure, neither a down regulation at the hANP receptor sites nor an hANP-induced shift from intra- to extravascular fluid volume are likely to be involved in its probably diabetes-specific pathogenesis.