Taner Damci

Study of Once Daily Levemir (SOLVE™): Insights into the timing of insulin initiation in people with poorly controlled type 2 diabetes in routine clinical practice

Aims: The aim of this analysis is to determine the timing of insulin initiation in routine clinical practice, especially in relation to glycaemic control and use of oral antidiabetic drugs (OADs).

Fenofibrate treatment is associated with better glycemic control and lower serum leptin and insulin levels in type 2 diabetic patients with hypertriglyceridemia

Background: Hertriglyceridemia is commonly encountered in type 2 diabetic patients. Fibrates are a group of drugs that efficiently decrease triglycerides, increase HDL, and improve the prognosis in both diabetic and nondiabetic patients. However, the effects of fibrates on glycemic control, blood pressure, fasting serum insulin, and leptin concentrations are not clear. The present study addresses the question of whether fenofibrate treatment in hypertriglyceridemic type 2 diabetic patients leads to changes in metabolic control, body mass index, leptin, free fatty acids, plasma insulin, and blood pressure. Methods: Thirty-one type 2 diabetic patients who had serum triglyceride levels between 250 and 400 mg/dl were included in the study. They were given 250 mg/day fenofibrate once daily for 3 months. Antidiabetic and antihypertensive treatments were kept unchanged throughout the study. Results: Fenofibrate treatment resulted in better glycemic control, as evidenced by lower fasting and postprandial blood glucose and HbAlc, decreased fasting serum insulin and leptin levels, as well as a reduction in hypertrigyceridemia and serum free fatty acids, and an increase in HDL cholesterol. Blood pressure, body mass index, and LDL remained unchanged. Fenofibrate was well tolerated in all patients. Conclusion: Fenofibrate treatment in hypertriglyceridemic type 2 diabetic patients is beneficial not only in terms of lipid profile, but also for glycemic control and insulin resistance.

Increased intestinal permeability as a cause of fluctuating postprandial blood glucose levels in Type 1 diabetic patients

Background In diabetic patients, postprandial glucose levels, which have a major impact on metabolic control, are determined by the rate of nutrient delivery into the intestine, absorption of nutrients from the small intestine, and the metabolism of the absorbed nutrients by the liver. The present study addresses whether Type 1 diabetic patients have increased intestinal permeability and intestinal permeability predicts postprandial glucose variability.

The safety and efficacy of adding once‐daily insulin detemir to oral hypoglycaemic agents in patients with type 2 diabetes in a clinical practice setting in 10 countries

Evaluate the safety and efficacy of once‐daily insulin detemir initiated in routine clinical practice in patients with type 2 diabetes mellitus inadequately controlled with oral hypoglycaemic agents (OHAs).

Nicotinamide Effects Oxidative Burst Activity of Neutrophils in Patients with Poorly Controlled Type 2 Diabetes Mellitus

Neutrophil functions are impaired in patients with diabetes mellitus. Bacterial phagocytosis and oxidative burst activity are reduced at high glucose concentrations in diabetic patients. Defects in neutrophil oxidative burst capacity are of multifactorial origin in diabetes mellitus and correlate with glucose levels. It has been reported that neutrophil NADPH oxidase activity is impaired and superoxide production is reduced in diabetic patients with or without any infections. Nicotinamide is a vitamin B3 derivative and a NAD precursor with immunomodulatory effects. In vitro studies demonstrated that nicotinamide increases NAD and NADH content of beta cells. The authors hypothesized that nicotinamide may restore the impaired oxidative burst capacity of neutrophils in diabetic patients by increasing the NADH content as an electron donor and possibly through NADPH oxidase activity of the cell. In order to test the hypothesis, this placebo-controlled and open study was designed to evaluate neutrophil functions in infection-free poorly controlled type 2 diabetic patients as compared to healthy subjects and assess the effects of nicotinamide on neutrophil phagocytosis as well as oxidative burst activity. Thirty patients with type 2 diabetes mellitus were enrolled in the study. Sixteen were females and 14 were males, with a mean age 58 ± 10. All patients were on sulphonylurea treatment and their hemoglobin A1c (HbA1c) levels were above 7.5%. The control group consisted of 10 voluntary healthy subjects. Diabetic and control subjects were not significantly different in terms of age, body mass index (BMI), leucocyte and neutrophil counts, C-reactive protein (CRP) level, and erythrocyte sedimentation rate (ESR), but HbA1c and fasting glucose levels were significantly higher in patients with diabetes mellitus. Phagocytic activity and respiratory burst indexes were measured by flow cytometric analyses as previously described by Rothe and Valet (Methods Enzyml., 233, 539–548, 1994) and compared in diabetic subjects and healthy controls. Diabetic patients were grouped to receive either 50 mg/kg oral nicotinamide (n = 15) or placebo (n = 15) for a period of 1 month. The 2 groups did not differ in terms of treatment, frequency of hypertension, BMI, diabetes duration, age, fasting plasma glucose (FPG), HbA1c, CRP, ESR, polymorphonuclear leukocyte (PNL) and neutrophil counts. Neutrophil functions were reassessed after the treatment period. Phagocytic activity represented as indexes were lower in diabetic patients when compared to healthy subjects, but the differences were not statistically significant (P > .05). Patients with diabetes mellitus had significantly lower oxidative burst indexes when compared to healthy controls (P values < .05). In diabetic patients, a negative correlation between neutrophil functions and HbA1c was found which was not statistically significant (P values > .05). Phagocytic indexes were similar in nicotinamide and placebo groups after treatment period (P > .05). But oxidative burst activity in patients receiving nicotinamide was greater when compared with placebo and the difference was statistically significant at 30 and 45 minutes (P values .04 and .03). This effect of nicotinamide may be due to increased NADH content and NADPH oxidase activity of the cell, which needs to be further studied. Impaired neutrophil functions may aggravate various infections in patients with diabetes mellitus and blood glucose regulation is an important target of treatment to improve neutrophil functions. But nicotinamide treatment may help to improve prognosis in diabetic patients with severe infections.

Incretin-based therapy in combination with basal insulin: A promising tactic for the treatment of type 2 diabetes

Incretin therapies such as dipeptidyl peptidase-4 inhibitors (DPP-4Is) and GLP-1 receptor agonists (GLP-1RAs) have become well-established treatments for type 2 diabetes. Both drug classes reduce blood glucose through physiological pathways mediated by the GLP-1 receptor, resulting in glucose-dependent enhancement of residual insulin secretion and inhibition of glucagon secretion. In addition, the GLP-1RAs reduce gastrointestinal motility and appear to have appetite-suppressing actions and, so, are often able to produce clinically useful weight loss. The glucose-dependency of their glucagon-inhibiting and insulin-enhancing effects, together with their weight-sparing properties, make the incretin therapies a logical proposition for use in combination with exogenous basal insulin therapy. This combination offers the prospect of an additive or synergistic glucose-lowering effect without a greatly elevated risk of hypoglycaemia compared with insulin monotherapy, and any insulin-associated weight gain might also be mitigated. Furthermore, the incretin therapies can be combined with metformin, which is usually continued when basal insulin is introduced in type 2 diabetes. Although the combination of incretin and insulin therapy is currently not addressed in internationally recognized treatment guidelines, several clinical studies have assessed its use. The data, summarized in this review, are encouraging and show that glycaemic control is improved and weight gain is limited or reversed (especially with the combined use of GLP-1RAs and basal insulin), and that the use of an incretin therapy can also greatly reduce insulin dose requirements. The addition of basal insulin to established incretin therapy is straightforward, but insulin dose adjustment (though not discontinuation) is usually necessary if the sequence is reversed.

Celiac disease in an adult Turkish population with type 1 diabetes mellitus.

Celiac disease is a frequent cause of morbidity among patients with type 1 diabetes mellitus. In this study our objective was to determine the prevalance of celiac diasease in a Turkish adult population with type 1 diabetes mellitus. Patients included 122 type 1 diabetes cases from adult diabetes clinic. Total IgA and IgA-antiendomysial antibody (AEA) assays were performed. Patients positive for IgA-AEA were asked to undergo small intestinal biopsy. Of the 122 patients, none was IgA deficient and 3 had positive IgA-AEA results (2.45%). All three of these patients had biopsies diagnostic of celiac disease. The body mass index (BMI) values of patients with positive AEA were significantly lower than normal (P = 0.024). Among the gastrointestinal complaints there was an association between early satiety and AEA positivity (P = 0.02). None of the other gastrointestinal complaints or age, duration of diabetes, glycosylated hemoglobin values, or insulin doses used were found to be related to AEA positivity. Celiac disease has a high prevalence among Turkish paients with type 1 diabetes mellitus. Screening for IgA-AEA during routine investigations of type 1 diabetic patients is important to prevent celiac-associated symptoms.

How important are the disturbances of lower gastrointestinal bowel habits in diabetic outpatients

1. Pei L, Melmed S. Isolation and characterization of a pituitary tumor-transforming gene. Mol Endocrinol 1997;11:433–4. 2. Kakar SS, Jennes L. Molecular cloning and characterization of the tumor transforming gene (TUTR1): A novel gene in human tumorigenesis. Cytogenet Cell Genet 1999;84:211–6. 3. Domı́nguez Á, Ramos-Morales F, Romero F, et al. hpttg, a human homologue of rat pttg, is overexpressed in hematopoietic neoplasms. Evidence for a transcriptional activation function of hPTTG. Oncogene 1998;17:2187–93. 4. Prezant TR, Kadioglu P, Melmed S. An intronless homolog of human proto-oncogene hPTTG is expressed in pituitary tumors. Evidence for hPTTG family. J Clin Endocrinol Metab 1999;84:1149–52. 5. Heaney AP, Singson R, McCabe CJ, et al. Expression of pituitary-transforming gene in colorectal tumors. Lancet 2000; 355:716–9. 6. Zhang X, Horwitz GA, Prezant TR, et al. Structure, expression, and function of human pituitary transforming gene (PTTG). Mol Endocrinol 1999;13:156–66. 7. Yajima T, Yagihashi A, Kameshima H, et al. Quantitative reverse transcription-PCR assay of the RNA component of human telomerase using TaqMan fluorogenic detection system. Clin Chem 1998;44:2441–5.

Sub-optimal drug treatment of diabetes and cardiovascular risk in diabetic patients in Turkey. A countrywide survey

OBJECTIVES The present study is a snapshot of how diabetic patients are treated for diabetes and coexisting cardiovascular risk factors in Turkey. We also addressed the question of what percentage of these patients are treated appropriately according to the current guidelines. Next step will be to determine which pharmacological treatment strategies affect mortality and morbidity in these patients and whether there are regional differences in these outcomes. METHODS To get a representative picture, Turkey was splitted into four parts with different ethnic and socioeconomic features then centers were randomized within each of these parts. Number of the centers in a region were calculated according to the population of that region. 305 physicians in 11 cities participated in data collection during a period of 3 months. Consecutive 2226 diabetic patients patients who were above 55 years of age were included. Detailed information was obtained about the demographic features and the cardiovascular risk factor and diabetes status of the patients together with relevant drug treatment. Laboratory analyses were done locally and recorded if performed during the last 3 months. RESULTS Most patients were treated with oral antidiabetic monotherapy regardless of diabetes duration, metabolic control and complication and cardiovascular risk factor status. There was a trend among physicians except for endocrinologists to underprescribe insulin. Monotherapy also was the main mode of treatment for hypertension. Angiotensin converting enzyme inhibitors were generally not used as first line treatment contrary to the recommendations and angiotensin converting enzyme inhibitors and angiotensin receptor blockers are not prescribed for renoprotection in microalbuminuric patients. Statins, fibrates, metformin and aspirin were largely underused. CONCLUSION The present study indicates that diabetic patients are undertreated in Turkey. Therefore every effort should be spent to implement current guidelines in diabetic patients in order to prevent macro and microvascular complications of diabetes.

Does instantaneous blood glucose affect vibration perception threshold measurement using biothesiometer

Diabetic neuropathy is a common and troublesome complication of diabetes mellitus. Vibration sensation is a measure of large fiber nerve conduction, which is very commonly affected in diabetes. The present study addresses the question of whether vibration perception threshold (VPT) measurement using a biothesiometer is reproducible under different levels of blood glucose at different hours of the day. Seventy-five diabetic patients, 31 insulin-dependent diabetes mellitus and 44 non-insulin-dependent diabetes mellitus, with mean age 50.33+/-14.22 years (21-70 years) and diabetes duration of 14.3+/-10.6 years (1-60 years) were included in the study. Forty-one patients were male and 34 were female. In conclusion, VPT was found to be reproducible under different blood glucose levels at different hours of the day, which is affected only by the height of the patient.