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The present study has been designed to determine melatonin levels in type 2 diabetic patients and test the relationship between the autonomic nervous system and melatonin dynamics. Thirty-six type 2 diabetic patients and 13 age-matched healthy subjects were recruited for the study. Circadian rhythm of melatonin secretion was assessed by measuring serum melatonin concentrations between 02:00-04:00 and 16:00-18:00 hr. Melatonin dynamics were re-evaluated with respect to autonomic nervous system in diabetic patients with autonomic neuropathy who were diagnosed by the cardiovascular reflex tests, heart rate variability (HRV), and 24-hr blood pressure monitoring. Nocturnal melatonin levels and the nocturnal melatonin surge were low in the diabetic group (P = 0.027 and 0.008 respectively). Patients with autonomic neuropathy revealed decreased melatonin levels both at night and during day when compared with healthy controls (P < 0.001 and 0.004 respectively) while the melatonin dynamics were similar to controls in patients without autonomic neuropathy. Nocturnal melatonin level was positively correlated with nocturnal high and low frequency components of HRV (P = 0.005 and 0.011 respectively) and systolic and diastolic blood pressures at night (P = 0.002 and 0.004 respectively) in patients with autonomic neuropathy. We found a negative correlation between nocturnal melatonin levels and the degree of systolic blood pressure decrease at night (r = -0.478, P = 0.045). As a conclusion this study has shown that circadian rhythm of melatonin secretion is blunted in type 2 diabetic patients and there is a complex relationship between various components of autonomic nervous system and melatonin secretion at night. Among the patients with autonomic neuropathy those with more preserved HRV and the systolic nondippers (<10% reduction in blood pressure during the night relative to daytime values) have more pronounced melatonin surge at night.

The pathogenesis of diabetic osteopenia is unclear. The markers of bone metabolism may show some changes in diabetic patients. In this study, we investigated the effect of glycemic control on serum osteocalcin level and urinary hydroxyproline excretion and the relations of these markers to duration of diabetes, C-peptide status, and body mass index. Twenty-seven men with poorly controlled diabetes mellitus (DM) (HbA1 > 9%, fasting plasma glucose > 7.8 mmol/liter) between ages 25 and 60 years (means +/- SD 46.6 +/- 10.4) were included in the study. Duration of diabetes was 5.8 +/- 4.7 years, body mass index (BMI) was 25 +/- 3.5 kg/m2, and fasting C-peptide was 2.33 (1.05-3.21) micrograms/liter. None of the patients had a disease or were treated with drugs that would interfere with calcium or phosphate metabolism and/or bone structure. They were free from chronic diabetic complications. Of these patients, 11 were lost to follow-up before metabolic control was achieved. The remaining 16 patients obtained good glycemic control (HbA1 < 8.3%, fasting plasma glucose < 7.8 mmol/liter) and completed the study. Serum osteocalcin level and urinary hydroxyproline excretion were determined before and after glycemic control. Urinary hydroxyproline excretion was not significantly changed by glycemic control [17.8 (7.1-23.2) versus 18.1 (10.9-28.1) mg/m2 day, P > 0.05]. However, serum osteocalcin level was significantly elevated (5.04 +/- 1.43 versus 4.17 +/- 1.83 micrograms/liter, P = 0.04). We found no correlation among fasting plasma glucose, HbA1, and fasting serum C-peptide levels with urinary hydroxyproline excretion. There was also no correlation between serum osteocalcin and fasting plasma glucose or serum C-peptide, but HbA1 was negatively correlated with serum osteocalcin (P = 0.01). No correlation was found between DM duration and BMI in the patients with serum osteocalcin level and urinary hydroxyproline excretion. To eliminate the possible effect of exogenous insulin on bone metabolism, the correlation analysis between the markers and C-peptide was further repeated in oral agents-treated patients. Serum C-peptide was not correlated to serum osteocalcin or urinary hydroxyproline in this subgroup of patients. Knowing that serum osteocalcin is a marker of bone formation, we concluded that osteoblast function may improve by glycemic control in diabetic patients; this may be due to correction of metabolic abnormalities associated with insulinopenia.

Acute effects of 20 mg oral enalapril (E), and angiotensin-converting enzyme inhibitor, on renal function and the renin-angiotensin-aldosterone system were investigated in 13 patients with type II diabetes mellitus (8 female, 5 male) and 10 hypertensive controls using a radionuclide method. Plasma glucose control was evaluated with fructosamine (F) determinations. After intravenous administration of 370 MBq 99mTc-DTPA, sequential images were recorded. Glomerular filtration rate (GFR), perfusion index (PI), time to maximum activity and reno index values of the kidneys were calculated. Two days later, renal scintigraphy was repeated after oral administration of E. Plasma levels of renin, angiotensin II and aldosterone were analyzed using RIA. Basal GFR values (mean: 92.6 ml/min) correlated with F (r = 0.364; p < 0.05). In the diabetic group, 5 patients had a decrease in GFR and an increase in PI after oral E. The mean percent change of GFR was 12 +/- 32 for patients and 20 +/- 12 for controls, respectively. Percent change of GFR had a slightly negative correlation with F values (r = -0.51; p < 0.05) and with PI (r = -0.65; p < 0.001). The patients with good metabolic control had an increase in GFR and a decrease in PI indicating an increase in renal blood flow and glomerular filtration. In patients with proteinuria and poorly controlled diabetes, in response to E-induced efferent arteriolar dilation, there is a decrease in GFR and an increase in PI which indicates a fall in filtration and renal blood flow. This glomerular hemodynamic pathology precedes morphological changes due to diabetes.