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To determine whether plasma endothelin, a potent vasoconstrictive peptide, is elevated in NIDDM patients, we compared a group of 15 NIDDM patients with macroangiopathy of mean age 60.60 +/- 2.33 years with 15 NIDDM randomly selected matched patients without macroangiopathy. Plasma endothelin levels were significantly increased in NIDDM patients with macroangiopathy (4.22 +/- 0.57 pmol/L) and in NIDDM patients without macroangiopathy (3.81 +/- 0.51 pmol/L). Although endothelin values did not differ between NIDDM groups, both represented significant difference from control values (2.46 +/- 0.24 pmol/L). No significant correlations were found between plasma endothelin and age (rs = 0.11), duration of diabetes mellitus (rs = 0.06), BMI (rs = 0.19), plasma glucose (rs = 0.15), plasma fructosamine (rs = 0.02). These findings confirm that in diabetes mellitus a primary disturbance in endothelin production from vascular endothelium exists as an early phenomenon rather than a result of advanced stage of the disease.

Conflicting evidence has been reported on the metabolic fate of glucose following oral ingestion. We measured the metabolic pattern of gluconeogenic substrates as alanine, predominantly produced by muscle, and lactate after an oral glucose load in ten normal subjects and in eighteen non-insulin dependent diabetes mellitus (NIDDM) subjects. Neither in normal or NIDDM subjects were significant increases in plasma alanine observed, whereas a significant increase in plasma lactate was observed at 60, 90 and 120 min after a glucose load. Although a similar behaviour in plasma alanine and lactate between normal and NIDDM subjects was found, in NIDDM significantly higher levels of plasma alanine and lactate were found at each time. From these observations we conclude: 1) when glucose is ingested under post-absorptive conditions, since plasma alanine levels do not change concurrently with lactate increase, muscle tissue does not play a predominant role in glucose disposal 2) after an oral glucose load, the pattern of gluconeogenic precursors (alanine and lactate) is similar in normal and NIDDM subjects 3) the main cause of fasting and post-prandial hyperglycemia in NIDDM subjects may be due to an overproduction of alanine as well as lactate.

Lipoprotein(a) [Lp(a)] has been added to the list of independent risk factors for cardiovascular disease (CVD), whose incidence is greater in obese subjects. There are few data available on the serum Lp(a) concentrations in obese individuals with or without insulin dependent diabetes mellitus (NIDDM). We selected 31 obese men with normal glucose tolerance (NGT) tests, 15 obese diabetic men, 14 non obese diabetic men and 17 healthy men as controls. We measured serum total cholesterol, HDL cholesterol, triglycerides, glucose, insulin and Lp(a). The mean Lp(a) levels in NGT obese men were 70.00 +/- 13.40 mg/l, which were similar to those found in normal controls (75.98 +/- 24.70 mg/l); significantly higher mean Lp(a) levels were found in obese diabetic men (168.84 +/- 56.43 mg/l) and in non obese diabetic men (240.85 +/- 63.35 mg/l). No significant correlation between Lp(a) levels and age, body mass index (BMI), total cholesterol, HDL cholesterol, triglycerides, insulin, was found; only a significant positive correlation between Lp(a) levels and glucose could be revealed (P < 0.05). Since higher levels of Lp(a) were found in NIDDM subjects with or without obesity, we conclude that hyperglycemia may influence the levels of serum Lp(a) facilitating its glycosylation in the liver with the consequence of a decline in its catabolic rate.

Several clinical and epidemiological evidences support the increased risk of cardiovascular disease (CVD) in pathological conditions as obesity, hypertension, non-insulin-dependent diabetes mellitus, which have hyperinsulinemia as a common feature. In this study, we assessed basal plasma insulin (IRI) and C-peptide (CPR) concentrations in 297 volunteers who participated in a survey concerning risk factors of CVD. We found a stepwise increase in fasting insulin and C-peptide levels in normal subjects (IRI 9.10 +/- 0.41 microU/ml; CPR 1.79 +/- 0.08 ng/ml), in obese subjects (IRI 11.31 +/- 0.38 microU/ml; CPR 2.54 +/- 0.07 ng/ml) in obese hypertensive subjects (IRI 14.17 +/- 0.72 microU/ml; CPR 2.64 +/- 0.09 ng/ml), in obese hypertensive diabetic subjects (IRI 22.57 +/- 2.62 microU/ml; CPR 3.33 +/- 0.27 ng/ml). Thus, we found increasing levels of IRI and CPR as normal conditions changed towards progressively more severe pathological conditions. Although several other factors contribute to determine CVD, we conclude that increasing levels of insulin and C-peptide could play an important role in causing CVD.

We determined erythrocyte glucose, ATP and lactate contents in diabetic subjects using an experimental design in which red blood cells (RBCs) were incubated over four hours in their own plasma and in plasma from normal subjects. The results indicated that baseline RBC glucose and lactate concentrations were higher in diabetic RBCs than in the controls, while ATP content was similar. After incubation, in diabetic RBCs glucose decreased significantly but more markedly when RBCs were incubated in normal plasma; lactate increased markedly in diabetic erythrocytes in their own plasma, but increased to the same extent as controls when incubated in normal plasma. ATP levels were similar to baseline values in diabetic RBCs in their own plasma, but decreased significantly when incubated in normal plasma. Since we found such a different metabolic behaviour in diabetic RBCs changing from diabetic to normal plasma, the important role of blood glucose in regulating RBC glycolysis is again confirmed.

We determined red blood cell (RBC) lactate concentrations in NIDDM subjects using an experimental protocol in which diabetic RBCs were incubated over 8 hours both with own plasma and with normal plasma. Furthermore, normal RBCs were incubated both with own plasma and with diabetic plasma. The results indicate that the increased lactate concentrations in RBCs from NIDDM subjects decreased significantly when the same RBCs were incubated in normal plasma. Conversely, lactate concentrations in normal RBCs increased significantly when RBCs were incubated in diabetic plasma. Thus, other than muscle and adipose tissue, RBCs may contribute to increase lactate release for hepatic gluconeogenesis in NIDDM and we suggest that there may be extrinsic plasmatic factor(s) capable of stimulatory effect on diabetic RBC glycolytic pathway.