Summary.We have studied the effects of vitamin D deficiency on pancreatic A-and B-cell function. Four subjects with vitamin D deficiency and 10 healthy subjects were studied. Pancreatic B-cell function was assessed by the insulin response to an oral glucose tolerance test. An insulin tolerance test was used to evaluate pancreatic A-cell function. The patients were then treated with 2000 U/day of vitamin D 3 for 6 months, after which the clinical, metabolic, biochemical and radiological features of vitamin D deficiency resolved, and pancreatic Aand B-cell function was repeated. In the vitamin D-deficient subjects pre-treatment and post-treatment serum calcium levels (mean _+ SEM) were 2.22+0.01mmol/1 and 2.24_+ 0.01 mmol/l respectively, and 2.27 _+ 0.02 mmol/l in healthy subjects (NS). The pre-treatment level of 1,25-dihydroxy vitamin D (1,25-(OH)2D) of 29.7 _+ 3.3 pg/ml in the vitamin D deficient subjects rose to 70.3 _+10.3 pg/ml after treatment (p < 0.05). The 1,25-(OH)2D level in the healthy subjects was 50.0 + 13.7 pg/ml (p < 0.05 versus pre-and post-treatment values in the patients). Insulin secretion, calculated by the area under the insulin curve, was significantly lower before vitamin D 3 treatment in the patients (9.09 + 0.7 mU x min, p<0.05) compared with the healthy subjects (11.9_+ 0.5 mU x min) and post-treatment values of the patients with vitamin D deficiency (13.7 + 0.5 mU x min). Similar changes were seen in the insulogenic indices (AI/AG). While AI/AG was 1.71 _+ 0.4 (mean + SEM) during vitamin D deficiency, it increased to 2.48_+0.3 with vitamin D repletion. The insulogenic index in the healthy subjects was 2.68 _+ 0.3. The glucose areas were not significantly different. Insulin-induced glucagon secretion was similar in all instances. The results of this study suggest that vitamin D deficiency reduces pancreatic insulin secretion but it does not affect pancreatic A-cell function.Key words: Vitamin D, insulin, glucagon secretion.Vitamin D is essential in higher animals and man for the maintenance of calcium and phosphorus homeostasis [1]. This is accomplished by the sequential metabolism of vitamin D by the liver and kidney into its principal biologically active metabolite, 1,25-dihydroxyvitamin D (1,25-(OH)2D) [2,3]. The effect of 1,25-(OH)2D has been associated with calcium and phosphate handling in intestine, bone and kidney. It has been established that 1,25-(OH)2D acts on these three tissues, as receptors for 1,25-(OH)2D have been found in these tissues [4][5][6]. Moreover, a large number of previously unrecognized target organs have been identified. Among them are stomach, skin, pituitary, brain and the endocrine pancreas [7][8]. Recent autoradiographic studies have provided evidence that 1,25-(OH)2D is selectively concentrated in and retained by pancreatic islet cells, suggesting a genomic action on B-cell function [8].Because of the known effects of vitamin D on membrane and calcium transport [9,10], abnormalities in vitamin D metabolism could alter endocrine cell membrane function and ...

Insulin resistance is a major feature of type 2 diabetes mellitus, obesity and nonalcoholic fatty liver disease (NAFLD). Several studies pointed out the possible role of increased leptin in NAFLD in humans. The aim of this study is to determine the effect of metformin on plasma leptin levels in obese patients with type 2 diabetes mellitus and NAFLD compared with lifestyle interventions. Thirty-four obese patients with newly diagnosed type 2 diabetes mellitus were prospectively followed for 6 months. All patients had ultrasonographic evidence of NAFLD at baseline. The patients were randomized into two groups: group 1 (n = 15) followed lifestyle changes only and group 2 (n = 19) received metformin (1,700 mg/day). At the end of treatment, BMI, WHR, HbA1c, fasting glucose, leptin, HOMA-IR, alanine aminotransferase values decreased in both groups. No significant difference in the end-points was observed between two groups. Only in group 2, LDL decreased and HDL increased significantly. Liver echogenity decreased significantly at the end of study in both groups. The percentage of patients who no longer had evidence of NAFLD was not significantly different between the groups (20% of patients on lifestyle intervention vs. 16% of patients on metformin). The data demonstrate that, metformin and lifestyle interventions equally affected the plasma leptin levels, BMI and degree of NAFLD in obese patients with type 2 diabetes mellitus. In addition, the effects of metformin on the variables were not found to be mediated by leptin.

In this cross-sectional study, we evaluated 15 premenopausal women to elucidate whether bone turnover is increased and bone mineral density is reduced due to endogenous subclinical hyperthyroidism. Each patient had normal free thyroxine (FT4) and free triiodothyronine (FT3) levels associated with a stable suppression (<0.1 mU/L) of serum thyrotropin (TSH) levels during a period ranging between 6 and 11 months. Metabolic parameters of bone turnover (serum osteocalcin, bone specific alkaline phosphatase, procollagen I C-terminal peptide reflecting bone formation; urinary deoxypyridinoline and calcium excretion reflecting bone resorption) were assessed. Bone mineral density was measured at lumbar 1-4 vertebrae, femoral neck, and the forearm (midshaft radius and distal radius) by dual energy x-ray absorptiometry. All measurements were compared with 15 healthy age-, height-, and weight-matched premenopausal women who served as control group. Our findings suggest that endogenous subclinical hyperthyroidism is not associated with increased bone turnover, and bone mineral density is not reduced in premenopausal women, at least in the short term.

Diabetic foot is a serious complication of diabetes mellitus and the risk of lower extremity amputation is very high in this population when compared with people without diabetes. We have previously reported the lower-extremity amputation rate and significant factors in determining the risks for patients who had been admitted to Hacettepe University Hospital, a tertiary reference center for Turkey, between the years 1992 and 1996. In January 2000, a diabetic foot care team including an infectious diseases specialist, orthopaedic surgeons, endocrinologists, a plastic and reconstructive surgeon, a radiologist, and a diabetic foot nurse was assembled. To determine whether a change has occurred in the rate and the risk factors of lower extremity amputations after the establishment of this team, medical records of 66 patients (39 men, 27 women) with diabetic foot who had been admitted to Hacettepe University Hospital between 2000 and 2002 have now been retrospectively analysed. The grade distribution of diabetic foot according to Wagner classification was quite similar in the two studies (grade 1: 0 % vs. 4.5 %, grade 2: 15.6 % vs. 19.7 %, grade 3: 48 % vs. 33.3 %, grade 4: 24.4 % vs. 30.3 %, grade 5: 11.5 % vs. 12.1 % in the former and current study, respectively). The overall amputation rate in the current study was 39.4 % (36.7 % in the former study). Ray amputation (35 %) and below-knee amputations (30 %) were the two most commonly applied procedures. The rates of Syme, above knee, other amputations (i.e., Boyd, talonavicular amputations and partial calcanectomy) were 8 %, 8 % and 19 %, respectively. These data suggest that amputation is still a frequently encountered outcome for our patients with diabetic foot, but the amputation profile has changed. The implementation of a diabetic foot care team has relatively decreased the rate of major amputations in an attempt for limb salvage to improve the quality of life of the patients. Presence of osteomyelitis, peripheral vascular disease and gangrene still remain as significant predictors of amputation in our population.

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.