Expert Opinion on the Utility of Telemedicine in Obesity Care: Recommendations on a Hybrid Multidisciplinary Integrated Care Follow-Up Algorithm.

PURPOSE OF REVIEW: The proposed expert opinion was prepared by a panel of obesity and law specialists from Turkey to review the utility of telemedicine in obesity care and to provide a guidance document with recommendations on a hybrid multidisciplinary integrated care follow-up algorithm and the legislation governing telemedicine practice to assist obesity specialists in practicing the telemedicine. RECENT FINDINGS: The efficacy and feasibility of telemedicine interventions in supporting obesity management programs even during pandemics confirm that obesity is a particularly well-suited field for telemedicine, emphasizing the strong likelihood of continued utilization of telemedicine in obesity management, beyond the pandemic period. Telemedicine has great potential to address several barriers to ongoing weight-management care, such as challenges of access to specialized care, cost, and time limitations as well as patient adherence to treatment. However, telemedicine practice should complement rather than replace the in-person visits which are unique in building rapport and offering social support. Accordingly, the participating experts recommend the use of a hybrid integrated care model in the management of obesity, with the use of telemedicine, as an adjunct to in-person visits, to enable the provision of suggested intensive obesity management via frequent visits by a multidisciplinary team of obesity specialists. Further research addressing the utility of telemedicine in terms of optimal modality and duration for successful long-term obesity management outcomes is necessary to develop specific guidelines on telemedicine practice. In addition, the legislation governing the norms and protocols on confidentiality, privacy, access, and liability needs to be improved.

Could the presence of adrenal incidentaloma negatively affect COVID 19 outcomes?

BACKGROUND AND OBJECTIVE: Adrenal incidentalomas (AIs) are lesions larger than 1 cm that are incidentally detected in the adrenal glands. Chest computed tomography (CCT) is widely used in the first evaluation of patients with suspected coronavirus disease (COVID-19) that resulted in many incidental findings in the thorax and upper abdomen. In this study, we aimed to investigate the frequency of AI and their effects on the course and outcome of COVID-19 regardless of functional status. MATERIAL AND METHODS: We included 2493 patients aged between 18 and 99 years and whose adrenal glands were clearly visible in CCT images. They were divided into two groups: those with AI (AI group) and without AI (Control group). RESULTS: AI was detected in 148 (5.93%) patients and 80 (54.1%) of them were male. There was no difference in sex distribution between the groups, but the median age of patients with AI was significantly higher than those without AI [54.5 (20-94 years) vs. 42 (18-99 years); p < 0.001)]. In addition, in the AI group, both hospitalizations due to COVID-19-related conditions (30.4 vs. 21.2%, p = 0.008) and the mortality rate experienced during this time was significantly higher (14.7 vs. 7%, p < 0.001) diseases. The AI group had a significantly higher comorbidity rate than the control group (61.5 vs. 41.9%, p < 0.001). The most common comorbid diseases were hypertension, cardiovascular diseases, diabetes mellitus, respiratory system diseases, and hyperlipidaemia. Advanced age and male gender in terms of mortality, advanced age and covid 19 positivity in terms of hospitalization were determined as significant risk factors. CONCLUSIONS: The presence of AI may increase the morbidity and mortality rates associated with COVID-19, regardless of their functional status. Therefore, patients subjected to CCT imaging for COVID-19-related lung diseases should also be evaluated for AI. Careful follow-up of patients with COVID-19 and AI is necessary to monitor the progression of COVID-19.

Clinical Impact of Glucagon-Like Peptide-1 Receptor Analogs on the Complications of Obesity.

BACKGROUND: Obesity is a chronic disease associated with increased morbidity and mortality due to its complications. The aims of obesity treatment are primarily to accomplish weight loss, and prevention or treatment of its complications. Lifestyle changes along with behavioral therapy constitute the first-line treatment of obesity followed by pharmacotherapy. Glucagon-like peptide receptor analogs (GLP-1 RAs) are among the approved pharmacotherapy options. Their central effect on suppressing appetite results in considerable weight loss. However, their effect on the complications of obesity has not been very well recognized. This review aims to analyze the effects of GLP-1 RAs on the complications of obesity, as diabetes mellitus, hypertension, nonalcoholic steatohepatitis (NASH), cardiovascular diseases, polycystic ovary syndrome, infertility, obstructive sleep apnea (OSA), osteoarthritis, cancer and central nervous system problems. SUMMARY: Data from preclinical studies and clinical trials have been thoroughly evaluated. Effects regarding the complications as far as the scope of this review have covered can be summarized as blood glucose lowering, blood pressure lowering, resolution of NASH, improving major cardiovascular events, improving fertility and sex hormone levels, and improvement in OSA symptoms and in cognitive scores. Although the mechanisms are not fully elucidated, it is clear that the effects are not solely due to weight loss, but some pleiotropic effects like decreased inflammation, oxidative stress, and fibrosis also play a role in some of the complications. KEY MESSAGES: Treating obesity is not only enabling weight loss but ameliorating complications related to obesity. Thus, any antiobesity medication has to have some favorable effects on the complications. As far as the GLP-RA's analogs are concerned, there seems to be an improvement in many of the complications regardless of the weight loss effect of these medications.

Status of Weight Change, Lifestyle Behaviors, Depression, Anxiety, and Diabetes Mellitus in a Cohort with Obesity during the COVID-19 Lockdown: Turk-Com Study Group.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic led to a lockdown period. Confinement periods have been related to unhealthy lifestyle behaviors. Our study aimed to determine weight change, changes in eating and exercise habits, the presence of depression and anxiety, and diabetes mellitus (DM) status in a cohort of patients with obesity. METHODS: The study was undertaken in nine centers of Collaborative Obesity Management (COM) of the European Association for the Study of Obesity (EASO) in Turkey. An e-survey about weight change, eating habits, physical activity status, DM status, depression, and anxiety was completed by patients. The International Physical Activity Questionnaire (IPAQ) score was used to determine physical activity in terms of metabolic equivalents (METs). A healthy nutrition coefficient was calculated from the different categories of food consumption. The Patient Health Questionnaire (PHQ-9) and General Anxiety Disorder (GAD-7) Questionnaire  were used for determining depression and anxiety, respectively. RESULTS: Four hundred twenty-two patients (age 45 ± 12.7 years, W/M = 350/72) were included. The healthy nutrition coefficient before the pandemic was 38.9 ± 6.2 and decreased to 38.1 ± 6.4 during the pandemic (p < 0.001). Two hundred twenty-nine (54.8%) patients gained weight, 54 (12.9%) were weight neutral, and 135 (32.3%) lost weight. Patients in the weight loss group had higher MET scores and higher healthy nutrition coefficients compared with the weight gain and weight-neutral groups (p < 0.001). The PHQ and GAD scores were not different between the groups. Percent weight loss was related to healthy nutrition coefficient (CI: 0.884 [0.821-0.951], p = 0.001) and MET categories (CI: 0.408 [0.222-0.748], p = 0.004). One hundred seventy patients had DM. Considering glycemic control, only 12 (8.4%) had fasting blood glucose <100 mg/dL and 36 (25.2%) had postprandial BG <160 mg/dL. When patients with and without DM were compared in terms of dietary compliance, MET category, weight loss status, PHQ-9 scores, and GAD-7 scores, only MET categories were different; 29 (11.7%) of patients in the nondiabetic group were in the highly active group compared with 5 (2.9%) in the diabetic group. CONCLUSION: The COVID-19 lockdown resulted in weight gain in about half of our patients, which was related to changes in physical activity and eating habits. Patients with DM who had moderate glycemic control were similar to the general population in terms of weight loss but were less active.

Food Addiction Correlates with Psychosocial Functioning More Than Metabolic Parameters in Patients with Obesity.

Aim: To investigate the association of food addiction (FA) with the psychosocial functioning and metabolic parameters in obese patients seeking weight-loss treatment. Methods: Two hundred twenty-four obese patients (male/female: 28/196) with a mean age of 44.5 ± 13.4 years and body mass index (BMI) of 41.6 ± 7.2 were included in the study. After receiving sociodemographic data and medical history, detailed physical examination, including anthropometric measurements, was performed by an experienced physician. Blood samples were taken after 8-12 hr of fasting. The presence of FA was evaluated by using Yale Food Addiction Scale (YFAS). Psychological evaluation was performed by using a self-reported Patient Health Questionnaire-9 (PHQ-9) and health-related quality of life using the 36-item short-form health survey (SF-36). Results: Seventy-two of 224 (32.1%) patients met the criteria for FA, according to YFAS. The mean age of patients with FA was younger compared with patients without FA (P < 0.001). There was no statistically significant difference between the patients with and without FA in terms of BMI, fat percentage, and waist circumference (P = 0.440, P = 0.644, and P = 0.144, respectively). The depression frequency was significantly higher (61.1%, P < 0.001), while the SF-36 score of mental health was lower (P = 0.027) in patients with FA than in the patients without FA. Age- and sex-adjusted mean fasting plasma glucose level was lower in patients with FA (P = 0.021), but serum insulin levels, HOMA-IR (homeostasis model assessment of insulin resistance), HbA1c (hemoglobin A1c), lipid parameters, and vascular adiposity index were comparable. Conclusions: We found that FA frequency was very high in obese patients seeking treatment for weight loss, and it correlates with psychosocial functioning more than metabolic parameters.

The Association Between Olfaction and Taste Functions with Serum Ghrelin and Leptin Levels in Obese Women.

Purpose: To investigate the olfaction and taste functions in obese female patients and the association between serum ghrelin and leptin levels compared with healthy controls. Methods: Fifty-two obese women, who have a body mass index >30 kg/m2, and 15 healthy women were included in the study. After 8 hrs fasting, blood samples were taken for serum biochemical parameters, ghrelin, and leptin level measurement. For the quantitative assessment of olfactory function, all participants underwent an N-butanol threshold test and odor identification test using 12 Sniffin' Sticks® fragrance sticks. The gustatory function was tested by administering a whole-mouth above threshold test using sucrose solutions. Results: The sucrose taste threshold score in obese women was significantly higher than the controls (P = 0.004). We found positively significant correlation between serum ghrelin levels and n-butanol threshold scores in obese women (r = 0.300, P = 0.031). N-butanol smell threshold was not significantly different between the two groups (P = 0.149), while the Sniffin' Sticks smell test scores were significantly lower in obese women compared with the controls (P = 0.007). Serum leptin levels were also significantly higher in obese women (P < 0.001) although there was no significant difference in serum ghrelin levels between the two groups (P = 0.768). There was no correlation between serum leptin levels and Sniffin' Sticks scores, n-butanol, and sucrose taste threshold scores in obese women. Conclusions: These results might suggest that leptin, which is an anorexigenic peptide, may have a negative effect on taste and smell functions. More studies are warranted to elucidate the exact role of ghrelin secretion on olfaction and taste functions.

Impact of Obesity on the Metabolic Control of Type 2 Diabetes: Results of the Turkish Nationwide Survey of Glycemic and Other Metabolic Parameters of Patients with Diabetes Mellitus (TEMD Obesity Study).

BACKGROUND: Obesity is the main obstacle for metabolic control in patients with type 2 diabetes. Turkey has the highest prevalence of obesity and type 2 diabetes in Europe. The effect of obesity on the metabolic control, and the macro- and microvascular complications of patients are not apparent. OBJECTIVES: This nationwide survey aimed to investigate the prevalence of overweight and obesity among patients with type 2 diabetes and to search for the impact of obesity on the metabolic control of these patients. We also investigated the independent associates of obesity in patients with type 2 diabetes. METHODS: We consecutively enrolled patients who were under follow-up for at least 1 year in 69 tertiary healthcare units in 37 cities. The demographic, anthropometric, and clinical data including medications were recorded. Patients were excluded if they were pregnant, younger than 18 years, had decompensated liver disease, psychiatric disorders interfering with cognition or compliance, had bariatric surgery, or were undergoing renal replacement therapy. RESULTS: Only 10% of patients with type 2 diabetes (n = 4,648) had normal body mass indexes (BMI), while the others were affected by overweight (31%) or obesity (59%). Women had a significantly higher prevalence of obesity (53.4 vs. 40%) and severe obesity (16.6 vs. 3.3%). Significant associations were present between high BMI levels and lower education levels, intake of insulin, antihypertensives and statins, poor metabolic control, or the presence of microvascular complications. Age, gender, level of education, smoking, and physical inactivity were the independent associates of obesity in patients with type 2 diabetes. CONCLUSION: The TEMD Obesity Study shows that obesity is a major determinant of the poor metabolic control in patients with type 2 diabetes. These results underline the importance of prevention and management of obesity to improve health care in patients with type 2 diabetes. Also, the results point out the independent sociodemographic and clinical associates of obesity, which should be the prior targets to overcome, in the national fight with obesity.

Even Short-Term Telmisartan Treatment Ameliorated Insulin Resistance But Had No Influence on Serum Adiponectin and Tumor Necrosis Factor-Alpha Levels in Hypertensive Patients with Metabolic Syndrome.

BACKGROUND: We investigated the effect of short-term telmisartan usage in addition to lifestyle changes such as diet and exercise on insulin resistance, lipid metabolism, and serum adiponectin and tumor necrosis factor-alpha (TNF-α) levels in hypertensive patients with metabolic syndrome (MetS). METHODS: A total of 36 hypertensive patients with MetS were randomized to telmisartan and control groups in an open-labeled prospective study. RESULTS: There were significant decreases in anthropometric variables of patients according to baseline measurements in both groups at the end of the study. Serum insulin level and insulin resistance assessed by homeostasis model assessment-insulin resistance were decreased significantly in the telmisartan group (P = 0.040 and P = 0.034, respectively) compared with the controls, while there was no statistically significant change in the lipid profiles of the two groups. Serum adiponectin level was increased by 19.1% ± 41.7% in the telmisartan group, but intergroup analysis revealed no significant change. There was also no significant change in serum TNF-α level in either group. CONCLUSION: It has been observed that even short-term telmisartan treatment had favorable effects on insulin resistance and glucose metabolism compared with lifestyle changes alone. The fundamental effect of telmisartan treatment on insulin resistance renders it a good therapeutic option for hypertensive patients with MetS.

Exenatide treatment causes suppression of serum fasting ghrelin levels in patients with type 2 diabetes mellitus.

AIM: In the present study, we investigated the long-term effects of exenatide treatment on serum fasting ghrelin levels in patients with type 2 diabetes mellitus. METHODS: Type 2 diabetic patients, who were using metformin with and without the other antihyperglycemic drugs on a stable dose for at least 3 months, were enrolled in the study. BMI>35 kg/m2 and HbA1c>7.0% were the additional inclusion criteria. Oral antihyperglycemic drugs, other than metformin, were stopped, and metformin treatment was continued at 2000 mg per day. Exenatide treatment was initiated at 5 µg per dose subcutaneously (sc) twice daily, and after one month, the dose of exenatide was increased to 10 µg twice daily. Changes in anthropometric variables, glycemic control, lipid parameters and total ghrelin levels were evaluated at baseline and following 12 weeks of treatment. RESULTS: Thirty-eight patients (male/female = 7/31) entered the study. The mean age of patients was 50.5 ± 8.8 years with a mean diabetes duration of 8.5 ± 4.9 years. The mean BMI was 41.6 ± 6.3 kg/m2 and the mean HbA1c of patients was 8.9 ± 1.4%. The mean change in the weight of patients was -5.6 kg and the percentage change in weight was -5.2 ± 3.7% following 12 weeks of treatment. BMI, fasting plasma glucose and HbA1c levels of patients were decreased significantly (P < 0.001 and P < 0.001; respectively), while there was no change in lipid parameters. Serum fasting ghrelin levels were significantly suppressed following 12 weeks of exenatide treatment compared with baseline values (328.4 ± 166.8 vs 245.3 ± 164.8 pg/mL) (P = 0.024). CONCLUSION: These results suggest that the effects of exenatide on weight loss may be related with the suppression of serum fasting ghrelin levels, which is an orexigenic peptide.

Evaluation of olfaction and taste function in type 2 diabetic patients with and without peripheral neuropathy.

AIMS: Olfaction and gustation in patients with diabetes mellitus have great significance on quality of life, and their impairment may result in possible hazards. A limited number of studies have been performed to determine the alteration of both gustatory and olfactory function in type 2 diabetic patients with diabetic peripheral neuropathy (DPN). The aim of this study was to determine whether type 2 diabetic patients, with and without DPN, exhibit major olfactory and gustatory dysfunction using validated and dependable techniques. METHODS: An observational-analytical case-control study was conducted. Sixty patients with type 2 diabetes mellitus (T2DM) and 30 healthy control subjects with a mean age of 57.1 ± 8.4 were included in the study. Patients with T2DM were recruited from the endocrinology outpatient clinic. After clinical evaluation and electromyography examination, patients with T2DM were divided into the 2 groups, with and without DPN. After a 10-hour fasting period, blood samples were taken for the measurement of serum creatinine, lipids, and HbA1c. For the quantitative assessment of olfactory function, all participants underwent butanol threshold test and odour identification test. Gustatory function was tested administering a whole-mouth above-threshold test using sucrose solutions. RESULTS: The control subjects showed significantly higher Sniffin' sticks and butanol threshold scores than the diabetic patients without DPN (P = .001 and P = .009). No significant difference was found in the gustatory function test between these 2 groups (P = .116). Diabetic patients with DPN had lower Sniffin' sticks scores, butanol threshold scores, and higher sucrose thresholds compared to the controls (P < .001, P < .001, and P = .002). There were no significant differences between diabetic patients with or without DPN regarding Sniffin' sticks scores, butanol threshold, and sucrose thresholds (P = .302, P = .181, and P = .118). CONCLUSION: In conclusion, this study demonstrates that T2DM is associated with olfactory and gustatory dysfunction. The fact that there was no difference between the diabetic patients with and without DPN elicits the idea of central neuropathy. This novel finding might facilitate the addition of olfactory and gustatory tests to the methodological spectrum of afferent pathway investigations.

Exenatide Treatment Causes Suppression of Serum Ghrelin Levels following Mixed Meal Test in Obese Diabetic Women.

AIM: To investigate the effect of exenatide treatment on serum ghrelin levels in obese female patients with type 2 diabetes mellitus. METHODS: Fourteen female patients with type 2 diabetes mellitus being treated with metformin and exenatide were enrolled. A mixed meal test was applied to the patients while continuing with their daily medications. Blood samples were taken before and at 60, 120, and 180 minutes following mixed meal test to measure serum total ghrelin, glucose, and insulin levels. The following week, exenatide treatment of the patients was paused for 24 hours and the same experimental procedures were repeated. RESULTS: Serum ghrelin levels were suppressed significantly at 180 minutes with exenatide treatment compared with baseline (294.4 ± 57.5 versus 234.5 ± 59.4 pg/mL) (p < 0.001). Serum ghrelin levels at 180 minutes were statistically different when percentage change in serum ghrelin levels after mixed meal tests with and without exenatide usage were compared (p = 0.001). Estimated total area under the curve values for serum ghrelin concentrations was also significantly lower with exenatide compared with omitted treatment (p = 0.035). CONCLUSION: These results suggest that the effect of exenatide on weight loss may be related with the suppression of serum ghrelin levels, which is an orexigenic peptide.

Central injection of CDP-choline suppresses serum ghrelin levels while increasing serum leptin levels in rats.

In this study we aimed to test central administration of CDP-choline on serum ghrelin, leptin, glucose and corticosterone levels in rats. Intracerebroventricular (i.c.v.) 0.5, 1.0 and 2.0 µmol CDP-choline and saline were administered to male Wistar-Albino rats. For the measurement of serum leptin and ghrelin levels, blood samples were obtained baseline and at 5, 15, 30, 60 and 120 min following i.c.v. CDP-choline injection. Equimolar doses of i.c.v. choline (1.0 µmol) and cytidine (1.0 µmol) were administered and measurements were repeated throughout the second round of the experiment. Atropine (10 µg) and mecamylamine (50 µg) were injected intracerebroventricularly prior to CDP-choline and measurements repeated in the third round of the experiment. After 1 µmol CDP-choline injection, serum ghrelin levels were suppressed significantly at 60 min (P=0.025), whereas serum leptin levels were increased at 60 and 120 min (P=0.012 and P=0.017 respectively). CDP-choline injections also induced a dose- and time-dependent increase in serum glucose and corticosterone levels. The effect of choline on serum leptin and ghrelin levels was similar with CDP-choline while no effect was seen with cytidine. Suppression of serum ghrelin levels was eliminated through mecamylamine pretreatment while a rise in leptin was prevented by both atropine and mecamylamine pretreatments. In conclusion; centrally injected CDP-choline suppressed serum ghrelin levels while increasing serum leptin levels. The observed effects following receptor antagonist treatment suggest that nicotinic receptors play a role in suppression of serum ghrelin levels,whereas nicotinic and muscarinic receptors both play a part in the increase of serum leptin levels.

Serum macroprolactin levels in pregnancy and association with thyroid autoimmunity.

BACGROUND: To assess the contribution of macroprolactin to high serum prolactin levels and their association with thyroid status and thyroid autoimmunity during pregnancy. METHODS: 138 pregnant women who suspected of having thyroid dysfunction were studied and divided into three groups according to the thyroid status; group 1; euthyroidism (n 40), group 2; hypothyroidism (n 54), and group 3; hyperthyroid (n 44). Polyethylene glycol (PEG) precipitation method was used for detection of macroprolactin. A percentage recovery of 40 % or less is considered as macroprolactinemia. If macroprolactin was negative, the percentage of monomeric prolactin recovery (monoPRL %) after PEG precipitation was used for comparison between the groups. RESULTS: Macroprolactinemia was found in two patients (1.4 %) one from hypothyroid and other from euthyroid group. Basal prolactin levels in these patients were 400 and 403 ng/mL respectively. Referring to all patients, there was no correlation between PRL, macroPRL or monoPRL % with thyroid hormone status and also with the serum levels of thyroid antibodies (p > 0.05). A positive correlation was observed between the serum levels of PRL with TSH (p = 0.014 and r = 0.219), while a negative correlation was found with FT4 (p = 0.011 and r = -0.227). CONCLUSIONS: Despite the fact that serum prolactin levels were found to be high during pregnancy, the contribution of macroprolactin was found to be insignificant in our study. Unlike other auto immune diseases, we could not find any relationship between thyroid autoimmunity and PRL, macroPRL or monoPRL %. These results confirmed that measured prolactin was quite homogeneous during pregnancy.

Effect of sitagliptin monotherapy on serum total ghrelin levels in people with type 2 diabetes.

AIM: Sitagliptin is not associated with weight gain and has neutral effects on body weight. It is unclear whether sitagliptin treatment alters serum ghrelin levels in people with type 2 diabetes. METHODS: Forty-four subjects with type 2 diabetes were randomly assigned to receive sitagliptin or medical nutrition therapy (MNT) for 12 weeks. Changes in anthropometric variables, glycemic control, insulin resistance, lipid parameters, and total ghrelin levels were evaluated at baseline and following 12 weeks of treatment. RESULTS: Significant decreases in body weight and body mass index were observed over the entire study period in both treatment groups. Glycosylated hemoglobin and postprandial plasma glucose levels were statistically significant decreased in the groups receiving sitagliptin compared with baseline values (p=0.021 and p=0.021, respectively), while they were unchanged in the groups receiving MNT. There was a significant decrease in total ghrelin in the groups receiving sitagliptin (p=0.04) compared with baseline values but not in the groups receiving MNT (p=0.46) at the end of the 12 weeks. CONCLUSIONS: In this study of patients with type 2 diabetes, treatment with sitagliptin was associated with a significant decrease in serum ghrelin levels. These results suggest that the neutral effect of sitagliptin on weight might be associated with the suppression of fasting serum ghrelin levels.

Vitamin D receptor gene BsmI, FokI, ApaI, TaqI polymorphisms and bone mineral density in a group of Turkish type 1 diabetic patients.

Previous studies have suggested an influence of vitamin D receptor alleles on bone metabolism and on susceptibility to type 1 diabetes mellitus in different ethnic populations. We aimed to investigate the distribution of vitamin D receptor (VDR) alleles in relation to biochemical bone turnover parameters and bone densitometry measurements in a group of Turkish type 1 diabetic patients. One hundred and seventeen patients (M/F 57/60, 27.6 ± 7.3 y duration of diabetes 8.1 ± 6.3 y) and 134 healthy controls (M/F 61/73, 26.2 ± 5.3 y) were included in the study. Bone mineral density (BMD) was evaluated by dual-energy X-ray absorptiometry (DEXA). The vitamin D receptor gene (VDR) polymorphisms FokI, Bsm1, Apa1, and Taq1 were examined using a PCR-based restriction analysis. Serum levels of calcium, phosphor osteocalcin, intact parathyroid hormone, and C telopeptide were measured. Vitamin D receptor Bsm1 Fok1, Apa1, and Taq1 genotype distributions were not different between patient with diabetes and control groups. BMD was 0.77 ± 0.2 g/cm(2) vs. 0.97 ± 0.2 g/cm(2) (P = 0.0001) for the femur, 1.0 ± 0.1 g/cm(2) vs. 1.13 ± 0.1 g/cm(2) (P = 0.001) for type 1 diabetic patients and controls. Bone turnover markers were significantly lower in type 1 diabetic group. BMD measurements and bone metabolic markers were not different between the genotypes in either the patient with diabetes or the controls. The VDR gene polymorphisms, Bsm1, Fok 1, Apa1, and Taq1 showed no influence on bone metabolism in our group of type 1 diabetic patients.

Comparative effects of pioglitazone and rosiglitazone on plasma levels of soluble receptor for advanced glycation end products in type 2 diabetes mellitus patients.

Low levels of soluble receptor for advanced glycation end products (sRAGE) have been associated with the occurrence of vascular complications in patients with type 2 diabetes mellitus. Preliminary evidence has suggested that thiazolidinediones have the ability to modulate circulating levels of this molecule in the hyperglycemic milieu. The aim of this pilot study was to assess the differential effect of 2 different thiazolidinediones-pioglitazone and rosiglitazone-on plasma levels of sRAGE in type 2 diabetes mellitus patients. Sixty type 2 diabetes mellitus subjects were randomly assigned to receive pioglitazone (30 mg/d, n = 19), rosiglitazone (4 mg/d, n = 20), or placebo (medical nutrition therapy, n = 21) for 12 weeks. Changes in plasma glucose, glycosylated hemoglobin, insulin resistance (homeostasis model assessment), total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, and sRAGE were evaluated at baseline and after 12 weeks. At 12 weeks, the pioglitazone (P < .001) group had a significant increase from baseline in sRAGE values that was not seen in the medical nutrition therapy and rosiglitazone groups. We conclude that, in type 2 diabetes mellitus patients, pioglitazone-but not rosiglitazone-significantly raised sRAGE, which may contribute to its antiatherogenic effects.

Effect of rosiglitazone, metformin and medical nutrition treatment on arterial stiffness, serum MMP-9 and MCP-1 levels in drug naive type 2 diabetic patients.

The aim of the study was to evaluate the long-term effect of rosiglitazone and metformin monotherapy with medical nutrition treatment (MNT) and of MNT alone on arterial stiffness, serum monocyte chemoattractant protein (MCP)-1 and matrix metalloproteinase (MMP)-9 in drug naive patients with type 2 diabetes mellitus. Fifty type 2 diabetic patients were randomized to receive rosiglitazone 4 mg/day (n=19) or metformin 850 mg/day (n=16) with MNT or MNT alone (n=15), for 52 weeks. Arterial stiffness was assessed by using large and small artery elasticity index (SAEI and LAEI, respectively). SAEI, LAEI, serum MCP-1 and MMP-9 levels were measured at baseline and following 52 weeks of treatment. SAEI was improved only in the rosiglitazone group, and the difference was still statistically significant when the three groups were compared (p=0.024). There were no differences in LAEI in inter- and intragroup comparisons at the end of the study. Serum MMP-9 levels were decreased in the metformin (-13.5+/-34.8%, p=0.02) and rosiglitazone (-27.2+/-51.0%, p=0.023) groups compared with baseline values, whereas no significant change was seen in serum MCP-1 levels. These results suggest that rosiglitazone monotherapy has favorable effects on arterial stiffness compared with metformin monotherapy independent of glycemic control.

Comparison of composite whole body insulin sensitivity index derived from mixed meal test and oral glucose tolerance test in insulin resistant obese subjects.

Apart from fasting blood glucose (FBG) and insulin (FBI), oral glucose tolerance test (OGTT) is also used in calculating insulin sensitivity. During OGTT, insulin secretion may not reflect normal physiological insulin secretion. Based on this idea, hepatic and whole body insulin sensitivity rates were tested during OGTT and mixed meal test (MMT) in obese subjects. Thirty-one women with Quantitative Insulin Sensitivity Check Index (QUICKI) values below 0.350 and body mass index (BMI) >or=30 were included into the study. OGTT with 75-g glucose and MMT 300 kcal were applied to all cases. Data obtained from OGTT and MMT were used in the assessment of insulin sensitivity with Hemostasis of Model Assessment-Insulin Resistance (HOMA-IR) and Matsuda's Composite Whole Body Insulin Sensitivity Index (Matsuda's ISI). Mean BMI, FBG, and FBI were 36.8 +/- 3.9 kg/m(2), 100.5 +/- 0.10 mg/dl, 16.2 +/- 5.3 microg/ml, respectively. QUICKI was 0.31 +/- 0.01 and HOMA-IR was 3.71 +/- 0.88. Matsuda's ISI derived from OGTT was 6.96 +/- 3.35 and from MMT was 11.32 +/- 6.61. In analysis, it was demonstrated that there was a correlation between HOMA-IR, QUICKI, and Matsuda's ISIs derived from OGTT and MMT. Comparing the time periods separately, it was detected that despite similar increment in insulin levels, glucose levels were higher in OGTT than MMT at 15 and 30 min. Consequently, Matsuda's ISI was demonstrated to be effectively used with the data of MMT, as used with OGTT. Moreover, MMT was shown to be in parallel to physiologic insulin secretion and reflect pancreatic functions better compared to OGTT.

Evaluation of chromosome aberrations, sister chromatid exchange and micronuclei in patients with type-1 diabetes mellitus.

Oxidative stress-induced DNA damage seems to play a role in the pathogenesis of type-1 diabetes mellitus and its complications. Several in vitro assays have been used to measure the DNA damage produced by oxidative stress. In the present study, we aimed to investigate the frequency of sister chromatid exchange (SCE), chromosomal aberrations (CA) and micronuclei (MN) in type-1 diabetes mellitus patients compared with healthy controls. SCE, CA and MN tests were carried out with the blood-cell cultures from 35 type-1 diabetic patients and 15 healthy, age- and sex-matched control subjects. The mean age of the type-1 diabetic patients was 31.89 +/- 10.01 years, with a mean duration of the diabetes of 7.8 +/- 6.02 years. The mean level of HbA1c of the type-1 diabetic patients was 8.37+/-1.36%. Only three (8.5%) patients with type-1 diabetes mellitus had an HbA1c level below 7%. Patients with type-1 diabetes mellitus showed a higher frequency of SCE compared with controls (5.44 +/- 1.47 and 2.54 +/- 0.82, respectively, p < 0.001), but there was no significant correlation between the duration of diabetes, HbA1c and SCE. No significant difference was found in CA or MN frequency in type-1 diabetic patients compared with controls. In conclusion, these results suggest that type-1 diabetes mellitus is a condition with genomic instability characterized by an increased level of SCE. Hyperglycemia-induced oxidative stress may be the underlying factor of the increased SCE frequency.

The effect of metformin treatment on VEGF and PAI-1 levels in obese type 2 diabetic patients.

The aim of the study was to evaluate the effect of metformin on markers of endothelial function, vascular inflammation and factors of thrombosis in obese type 2 diabetic patients. Twenty-four type 2 diabetic patients (15 female, 9 male) previously under medical nutrition treatment (MNT)+regular exercise programme (REP) without chronic micro or macrovascular complications with the mean age of 50.5+/-1.5 years, diabetes duration of 17.9+/-6.3 months and body mass index (BMI) of 31.7+/-0.8 kg/m(2) were enrolled in the study. In the first 4 weeks, all the patients continued MNT+REP. In the following 12 weeks, metformin (mean daily dosage of 1381+/-85 mg) was added. After the first period with MNT+REP, BMI, waist circumference, fat percentage, blood pressure and HDL cholesterol decreased significantly. After metformin addition, there was a significant decrement in BMI, waist circumference, fat percentage, fasting and postprandial plasma glucose, hemoglobin A1C, plasminogen activator inhibitor-1 (PAI-1), vascular endothelial growth factor (VEGF) and increment in beta cell reserve values of the patients. Our results indicated that, metformin addition had beneficial effect on VEGF and PAI-1 levels in obese type 2 diabetic patients under MNT+REP, independent from its' favourable effects on BMI and glycemic control.