Effects of different metabolic states and surgical models on glucose metabolism and secretion of ileal L-cell peptides: results from the HIPER-1 study.

AIM: To compare the impact of four surgical procedures (mini-gastric bypass, sleeve gastrectomy, ileal transposition and transit bipartition) vs medical management on gut peptide secretion, ß-cell function and resolution of hyperglycaemia in people with type 2 diabetes. RESEARCH DESIGN AND METHODS: A mixed-meal tolerance test was administered 6-24 months after each surgical procedure (mini-gastric bypass, sleeve gastrectomy, ileal transposition and transit bipartition; n=30 in each group) and the results were compared with those obtained in matched lean (n=30) and obese (n=30) people with type 2 diabetes undergoing medical management. RESULTS: Participants in the mini-gastric bypass and ileal transposition groups had a greater increase in plasma glucose concentration after the mixed-meal tolerance test than those in the sleeve gastrectomy and transit bipartition groups. Participants in the mini-gastric bypass group exhibited the greatest increase in the incremental area under the curve of plasma glucose concentration above baseline (P<0.0001). Insulin sensitivity was similar across surgical groups, and statistically greater in participants in the surgical groups than in obese participants in the non-surgical group (P<0.0001). ß-cell responsiveness to glucose was greater in participants in the sleeve gastrectomy and transit bipartition groups than in the mini-gastric bypass and ileal transposition groups (P<0.001) despite a smaller incremental increase above baseline in the area under the plasma glucagon-like peptide-1 concentration curve relative to ileal transposition. Postoperative ß-cell function was the strongest predictor of hyperglycaemia resolution. CONCLUSIONS: The present study showed that the level of ß-cell function after bariatric surgery is the strongest predictor of hyperglycaemia resolution. The study also demonstrates a disconnect between postprandial GLP-1 levels and ß-cell function among the studied surgical procedures.

The protective effect of losartan on diabetic neuropathy in a diabetic rat model.

AIM: Involvement of the peripheral and autonomic nervous systems is possibly the most frequent complication of diabetes. Important risk factors included hyperglycemia, dyslipidemia, hypertension, and smoking. Angiotensin-converting-enzyme inhibitor (ACE) inhibitors should be beneficial in all vascular beds, including neuropathy and retinopathy. In this study we aimed to evaluate the effect of the angiotensin receptor blocker losartan on diabetic neuropathy in a diabetic rat model. MATERIAL AND METHODS: 24 male, Sprague Dawley albino mature rats were divided into 3 groups; (1) control group: No drug was administered to the remainder of rats which blood glucose levels were under 120 mg/dl, (2) diabetic control: rats were given no medication, but 4 ml per day of tap water was given by oral gavage, (3) losartan groups: rats were given 10 mg/kg/day oral of losartan for 4 weeks. Electromyography (EMG) was applied to anesthetized rats at the end of 4(th) weekend. Then, the animals were euthanized and sciatic nerve was performed for histopathological examination. RESULTS: Compound Muscle Action Potential (CMAP) amplitude of diabetic rats receiving the Saline in the EMG was significantly reduced when compared to the control group. Distal latency value and CMAP duration of diabetic rats receiving the saline were meaningfully increased when compared to the control group. CMAP amplitude and CMAP duration of diabetic rats receiving the Losartan treatment in the EMG were meaningfully reduced when compared to diabetic rats receiving the Saline.Perineural thickness in the rats receiving the Losartan treatment was found to be significantly reduced when compared to the group receiving the Saline. CONCLUSIONS: As a result, it has been shown in this study that perineural thickness of the Losartan treatment was significantly reduced when compared to saline receiving group, significantly increased the immunoexpression of NGF, and also provided a significantly recovery in EMG when compared to Saline receiving group.

Plasma osteoprotegerin concentrations in type 2 diabetic patients and its association with neuropathy.

BACKGROUND AND AIMS: To investigate the association of plasma osteoprotegerin (OPG) levels with diabetic neuropathy. METHODS: Forty-two diabetic patients (21 female and 21 male) and twenty-four non-diabetic healthy control subjects (12 female and 12 male) were included in the study. All consecutive diabetic patients who came for routine follow-up at our outpatient clinic were invited to participate in this clinical study. We studied EMG and neuropathy symptom score in all study subjects. Fasting plasma glucose, HbA1 C, hs-CRP, OPG levels and lipid profile were measured for each subject. RESULTS: Serum fasting glucose, HbA1c, HOMA-IR, total cholesterol, triglyserid, LDL-Cholesterol, HDL-Cholesterol, lipoprotein (a), apolipoprotein-b, hs-CRP, OPG levels, and neuropathy symptom score were statistically higher in diabetic patients than in healthy control subjects. Plasma OPG levels was statistically higher in diabetic patients than it was in nondiabetic control subjects. However, plasma OPG levels were not significantly different between diabetic patients without neuropathy and healthy control subjects. On the other hand, OPG levels were statistically higher in diabetic patients with neuropathy than in patients without neuropathy. In addition to that serum fasting glucose, HbA1c, hs-CRP, diabetes duration, neuropathy symptom score were statistically higher in diabetic patients with neuropathy than they were in patients without neuropathy. In total group of subjects, plasma OPG levels were correlated significantly with age, diabetes duration, HbA1c, total cholesterol, HDL-cholesterol, lipoprotein (a), apolipoprotein b, hs-CRP. In diabetic patients, plasma OPG correlated significantly with age, diabetes duration, neuropathy symptom score, HbA1c, lipoprotein (a), apolipoprotein b levels. CONCLUSIONS: The major findings of this study were that the plasma OPG concentrations were higher in type 2 diabetic patients than OPG concentrations in healthy control subjects and they were positively correlated with diabetic neuropathy. This finding supports the growing concept that OPG acts as an important regulator in the development of vascular dysfunction in diabetes.