Obese Type 2 Diabetes Patients Research Articles

Effect of the Duodenal-Jejunal Bypass Liner on Glycemic Control in Patients With Type 2 Diabetes With Obesity: A Meta-analysis With Secondary Analysis on Weight Loss and Hormonal Changes

Duodenal-jejunal bypass liner (DJBL) is an endoscopic device that may mimic small bowel mechanisms of Roux-en-Y gastric bypass (RYGB). Previous studies have demonstrated the efficacy of DJBL at inducing weight loss. We assessed the effect of DJBL on glycemic control in patients with type 2 diabetes (T2D) with obesity. Data sources included MEDLINE, EMBASE, and Web of Science through 1 July 2017. Included were published studies that assessed DJBL outcomes in obese T2D patients. Primary outcomes were change in HbA1c and HOMA of insulin resistance (HOMA-IR). Secondary outcomes were change in weight and gut hormones glucose-dependent insulinotropic peptide (GIP), glucagon-like peptide 1 (GLP-1), peptide YY (PYY), and ghrelin. Seventeen studies were included. At explant, HbA1c decreased by 1.3% [95% CI 1.0, 1.6] and HOMA-IR decreased by 4.6 [2.9, 6.3]. Compared with control subjects, DJBL subjects had greater HbA1c reduction by 0.9% [0.5, 1.3]. Six months after explant, HbA1c remained lower than baseline by 0.9% [0.6, 1.2]. At explant, patients lost 11.3 kg [10.3, 12.2], corresponding to a BMI reduction of 4.1 kg/m2 [3.4, 4.9], total weight loss of 18.9% [7.2, 30.6], and excess weight loss of 36.9% [29.2, 44.6]. The amount of weight loss remained significant at 1 year postexplantation. After DJBL, GIP decreased, whereas GLP-1, PYY, and ghrelin increased. DJBL improves glycemic control and insulin resistance in T2D patients with obesity. DJBL also appears to induce significant weight loss in this population. Additionally, changes in gut hormones suggest mechanisms similar to RYGB. Study limitations included heterogeneity among studies.

Patients characteristics associated with better glycemic response to teneligliptin and metformin therapy in type 2 diabetes: a retrospective study

Background: Teneligliptin was recently approved for type 2 diabetes (T2D) management in India and is used as monotherapy or in combination with different antidiabetic drugs. The aim of this study was to identify patients’ characteristics associated with better glycemic response to teneligliptin and metformin.Methods: A retrospective analysis of data was performed in patients of T2D with HbA1c above 7% who were treated with teneligliptin 20 mg/d as add on to metformin (500-100 mg/d) and whose follow-up data at 12-weeks was available. Fasting blood sugar (FBS) and post-prandial blood sugar (PPBS) changes were analysed. Results: Among 66 patients included in analysis, mean age was 61.0±9.8 years and 53% were females. Median duration of diabetes was 2 years. At 12-weeks, a significant reduction PPBS was observed (mean change: -14.3 mg/dL, p=0.009) but not in FBS (mean change: -2.4 mg/dL, p=0.353). Among different patients’ characteristics, age ≤60 years (p=0.006), duration of ≤1 year (p=0.023), body-mass index ≥25 kg/m2 (p=0.009), presence of dyslipidemia (p=0.05) and absence of complications (p=0.012) were associated with significant reduction in PPBS but not in FBS.Conclusions: A younger, newly-diagnosed, obese T2D patients with dyslipidemia without any complications of diabetes can derive better therapeutic effectiveness from teneligliptin added to metformin. These findings need to be confirmed in large, prospective, long duration study.

Caloric restriction lowers endocannabinoid tonus and improves cardiac function in type 2 diabetes

Background/ObjectivesEndocannabinoids (ECs) are associated with obesity and ectopic fat accumulation, both of which play a role in the development of cardiovascular disease (CVD) in type 2 diabetes (T2D). The effect of prolonged caloric restriction on ECs in relation to fat distribution and cardiac function is still unknown. Therefore, our aim was to investigate this relationship in obese T2D patients with coronary artery disease (CAD).Subjects/MethodsIn a prospective intervention study, obese T2D patients with CAD (n = 27) followed a 16 week very low calorie diet (VLCD; 450–1000 kcal/day). Cardiac function and fat accumulation were assessed with MRI and spectroscopy. Plasma levels of lipid species, including ECs, were measured using liquid chromatography-mass spectrometry.ResultsVLCD decreased plasma levels of virtually all measured lipid species of the class of N-acylethanolamines including the EC anandamide (AEA; −15%, p = 0.016), without decreasing monoacylglycerols including the EC 2-arachidonoylglycerol (2-AG). Baseline plasma AEA levels strongly correlated with the volume of subcutaneous white adipose tissue (SAT; R2 = 0.44, p < 0.001). VLCD decreased the volume of SAT (−53%, p < 0.001), visceral white adipose tissue (VAT) (−52%, p < 0.001), epicardial white adipose tissue (−15%, p < 0.001) and paracardial white adipose tissue (−28%, p < 0.001). VLCD also decreased hepatic (−86%, p < 0.001) and myocardial (−33%, p < 0.001) fat content. These effects were accompanied by an increased left ventricular ejection fraction (54.8 ± 8.7–56.2 ± 7.9%, p = 0.016).ConclusionsCaloric restriction in T2D patients with CAD decreases AEA levels, but not 2-AG levels, which is paralleled by decreased lipid accumulation in adipose tissue, liver and heart, and improved cardiovascular function. Interestingly, baseline AEA levels strongly correlated with SAT volume. We anticipate that dietary interventions are worthwhile strategies in advanced T2D, and that reduction in AEA may contribute to the improved cardiometabolic phenotype induced by weight loss.

Should Roux-en-Y gastric bypass biliopancreatic limb length be tailored to achieve improved diabetes outcomes?

The objective is to access the role of Roux-en-Y gastric bypass (RYGB) biliopancreatic limb (BPL) length in type 2 diabetes (T2D) outcomes.RYGB is more effective than medical intervention for T2D treatment in obese patients. Despite the scarcity of available data, previous reports suggest that modifications of the RYGB limb lengths could improve the antidiabetic effects of the surgery.A cohort of obese T2D patients (n = 114) were submitted to laparoscopic RYGB, either with a standard BPL (SBPL) (n = 41; BPL 84 ± 2 cm) or long BPL (LBPL) (n = 73; BPL = 200 cm) and routinely monitored for weight loss and diabetic status up to 5 years after surgery.Baseline clinical features in the 2 patient subgroups were similar. After surgery, there was a significant reduction of body mass index (BMI) in both the groups, although the percentage of excess BMI loss (%EBMIL) after 5 years was higher for LBPL (75.50 ± 2.63 LBPL vs 65.90 ± 3.61 SBPL, P = .04). T2D remission rate was also higher (73% vs 55%, P < .05), while disease relapse rate (13.0% vs 32.5%; P < .05) and antidiabetic drug requirement in patients with persistent diabetes were lower after LBPL. Preoperative T2D duration predicted disease remission, but only for SBPL.RYGB with a longer BPL improves %EBMIL, T2D remission, and glycemic control in those with persistent disease, while it decreases diabetes relapse rate over time. The antidiabetic effects of LBPL RYGB also are less influenced by the preoperative disease duration. These data suggest the RYGB procedure could be tailored to improve T2D outcomes.

Diabetes Outcomes More than a Decade Following Sustained Weight Loss After Laparoscopic Adjustable Gastric Band Surgery.

Long-term outcome data are needed to define the role of bariatric surgery in type 2 diabetes (T2D). To address this, we collated diabetes outcomes more than a decade after laparoscopic adjustable gastric band (LAGB) surgery. Clinical and biochemical measures from 113 obese T2D patients who underwent LAGB surgery in 2003 and 2004 were analyzed. Diabetes remission was defined as HbA1c <6.2% (44mmol/mol) and fasting glucose <7.0mmol/L. Seventy-nine patients had weight data at 10years and attained a median [Q1, Q3] weight loss of 16 [10, 21] percent. Sixty patients attended a follow-up assessment. Their baseline HbA1c of 7.8 [7.1, 9.3] percentage units (62 [54, 78] mmol/mol) had decreased to 6.6 [6.1, 8.4] (49 [43, 68] mmol/mol) despite no significant change in glucose-lowering therapy. Eleven patients (18%) were in diabetes remission and another 18 had HbA1c≤6.5%. Significant improvements in physical measures of quality of life, blood pressure, and lipid profile were also observed but there was no change in the proportion of patients with albuminuria and a significant decline in estimated glomerular filtration rate. Twelve patients in the follow-up cohort (20%) required anti-reflux medication after surgery and 26 (43%) underwent gastric band revision surgery. Weight loss for over 10years after LAGB surgery delivers clinically meaningful improvements in HbA1c, blood pressure, lipids, and quality of life at the cost of a high rate of revision surgery and increased use of anti-reflux medication. These findings support the use of bariatric surgery as a long-term treatment for weight loss and wellbeing in patients with T2D. Registered with the Australian Clinical trials registry as ACTRN12615000089538.

Obesity, type 2 diabetes, and impaired insulin-stimulated blood flow: role of skeletal muscle NO synthase and endothelin-1.

Although impairments in endothelial signaling are hypothesized to reduce insulin-stimulated blood flow in type 2 diabetes (T2D), human studies examining these links are limited. We provide the first measures of nitric oxide synthase and endothelin-1 expression from skeletal muscle tissue containing native microvessels in individuals with and without T2D before and during insulin stimulation. Higher basal skeletal muscle expression of endothelin-1 and reduced endothelial nitric oxide phosphorylation (peNOS)/eNOS may contribute to reduced insulin-stimulated blood flow in obese T2D patients.

The IGF-Axis and Diabetic Retinopathy Before and After Gastric Bypass Surgery.

Laparoscopic gastric bypass (LGB) abruptly causes remission of type 2 diabetes (T2D). Such dramatic metabolic changes have previously been found to cause worsening of diabetic retinopathy (DR) and circulating insulin-like growth factor I (IGF-I) has been suggested as a causal mediator. We aimed to evaluate baseline imbalances in the circulating IGF-system and changes after LGB in patients with T2D. Prospective ocular examinations and measurement of the IGF-axis before and 3 and 12months after LGB. IGF-bioactivity was measured by cell-based IGF-I receptor (IGF-IR) kinase activation assay (bioactive IGF). Total IGF-I, IGF-II and IGF binding protein (IGFBP) 1 and 3 were determined by immunoassays. At baseline, 18 of 36 patients presented with DR. These patients had higher levels of bioactive IGF (p=0.03) than patients without DR and this association was strengthened in multivariate analysis (p=0.006). Three patients had worsening of DR, unrelated to other markers. In univariate analysis, bioactive IGF increased at 3months (p=0.05) but this change became insignificant in multivariate analysis (p=0.11). IGFBP-1 increased whereas IGFBP-3 and total IGF-II decreased at the two postoperative visits (p≤0.001). Total IGF-I showed no significant changes. HbA1c, glucose, HOMA-IR and lipids improved after surgery. Two patients did not complete the 12-month visit. In obese T2D patients, bioactive IGF is a potential biomarker for DR and levels tended to increase 3months after bariatric surgery. IGFBP-1 increased while IGFBP-3 and total IGF-II decreased postoperatively, but these changes were unassociated with the development of DR. Markers of the metabolic syndrome improved.

Restoration of high-frequency glucose-entrained insulin oscillations in obese subjects with type 2 diabetes after biliopancreatic diversion

BackgroundMinimal glucose infusions are known to entrain insulin oscillations in patients with normal glucose tolerance (NGT) but not in patients with type 2 diabetes (T2D). ObjectivesTo investigate whether weight loss after a version of biliopancreatic diversion (BPD) can restore the glucose entrainment of high-frequency insulin oscillations in morbidly obese NGT or T2D patients. SettingUniversity Hospital, Greece. MethodsWe prospectively studied 9 NGT controls (body mass index [BMI] 23.3±1.6 kg/m2), 9 obese NGT patients (BMI 51.1±12.7 kg/m2), and 9 obese T2D patients (BMI 56.8±11.6 kg/m2). Patients were studied before and 1.5 years after BPD. Insulin was sampled every minute for 90 minutes. Glucose (6 mg/kg weight) was infused every 10 minutes for 1 minute. Regularity of insulin pulses was estimated by autocorrelation analysis, spectral analysis, approximate entropy/sample entropy (ApEn/SampEn), and insulin pulsatility by deconvolution analysis. ResultsPostoperatively, glucose and insulin concentrations of NGT and T2D patients decreased to control levels and BMI to 31.3±6.3 for NGT patients and 34.9±9.9 kg/m2 for T2D patients. Preoperatively, glucose entrainment was absent in all T2D and in 4 NGT patients as assessed with spectral analysis and in 8 and 4, respectively, as assessed with autocorrelation and deconvolution analysis. Postoperatively, it was restored to normal in all patients. ApEn/SampEn decreased significantly only in the T2D group postoperatively. ConclusionBPD restores the glucose entrainment of high-frequency insulin oscillations in obese NGT and T2D patients after marked weight loss and normalizes glucose levels and insulin sensitivity, thus demonstrating recovery of β-cell glucose sensing.

Interleukin-1 signaling contributes to acute islet compensation.

IL-1β is a well-established inducer of both insulin resistance and impaired pancreatic islet function. Despite this, findings examining IL-1 receptor deficiency or antagonism in in vivo animal models, as well as in clinical studies of type 2 diabetic (T2D) patients, have led to conflicting results, suggesting that the actions of IL-1β on glycemic control may be pleiotropic in nature. In the present work, we find that the ability of IL-1β to amplify glucose-stimulated insulin secretion from human islets correlates with donor BMI. Islets from obese donors are sensitized to the insulinotropic effects of this cytokine, whereas the stimulatory effects of IL-1β are lost in islets from obese T2D patients, suggesting a role for IL-1 signaling in islet compensation. Indeed, mice deficient in IL-1 receptor type I become glucose intolerant more rapidly than their WT littermates and have impaired secretory responses during the acute stages of inflammatory and metabolic stress induced by LPS and high-fat diet, respectively. IL-1β directly enhances β cell insulin secretion by increasing granule docking and soluble N-ethylmaleimide-sensitive factor attachment receptor (SNARE) complex formation at the plasma membrane. Together, our study highlights the importance of IL-1β signaling in islet compensation to metabolic and inflammatory stress.

Conserved Metabolic Changes in Nondiabetic and Type 2 Diabetic Bariatric Surgery Patients: Global Metabolomic Pilot Study.

The goal of this study was to provide insight into the mechanism by which bariatric surgical procedures led to weight loss and improvement or resolution of diabetes. Global biochemical profiling was used to evaluate changes occurring in nondiabetic and type 2 diabetic (T2D) patients experiencing either less extreme sleeve gastrectomy or a full gastric bypass. We were able to identify changes in metabolism that were affected by standard preoperation liquid weight loss diet as well as by bariatric surgery itself. Preoperation weight-loss diet was associated with a strong lipid metabolism signature largely related to the consumption of adipose reserves for energy production. Glucose usage shift away from glycolytic pyruvate production toward pentose phosphate pathway, via glucose-6-phosphate, appeared to be shared across all patients regardless of T2D status or bariatric surgery procedure. Our results suggested that bariatric surgery might promote antioxidant defense and insulin sensitivity through both increased heme synthesis and HO activity or expression. Changes in histidine and its metabolites following surgery might be an indication of altered gut microbiome ecology or liver function. This initial study provided broad understanding of how metabolism changed globally in morbidly obese nondiabetic and T2D patients following weight-loss surgery.

“Dual-remission” after Roux-en-Y gastric bypass surgery: Glycemic variability cannot always be improved in Chinese obese patients with type 2 diabetes

BackgroundGlycemic variability after Roux-en-Y Gastric Bypass (RYGB) has not been adequately examined in Chinese obese patients with type 2 diabetes (T2D). ObjectiveWe aimed to evaluate glucose variability after RYGB by continuous glucose monitoring (CGM) and then evaluate the remission rate based on the complete diabetes remission criteria combined with normal ranges of CGM for the Chinese population, which we defined as “dual-remission.” SettingThe study was done at our academic university-affiliated hospital. MethodsOver a 3-day period, CGM was performed on 43 Chinese obese T2D patients combined with a mixed-meal test before and 1 year after RYGB. Mean amplitude of glucose excursions (MAGE), standard deviations (SD), and the time that patients’ blood glucose levels were≥7.0 mmol/L,≥7.8 mmol/L,≥11.1 mmol/L, and≤3.9 mmol/L within 24 hours was analyzed. Multiple logistic regression analyses were used to identify predictors of “dual-remission.” ResultsComplete diabetes remission was achieved in 27 patients (62.8%) 1 year after RYGB. However, MAGE didn’t change in the group, and only 18.6% patients met “dual-remission.” Compared with patients in the complete remission group, patients in the dual-remission group had a shorter duration of diabetes, younger age, lower glycated hemoglobin (HbA1c) level, and no insulin usage at baseline. Correlation analysis showed MAGE after RYGB was positively correlated with diabetes duration (r = .43, P<.01). Multiple logistic regressions indicated a shorter duration was associated with a higher possibility to achieve dual-remission after adjusting for age, gender, HbA1c, and insulin therapy. ConclusionGlucose variability can’t be effectively improved in most Chinese obese diabetic patients after RYGB. Shorter diabetes duration was associated with higher possibility to achieve “dual-remission.”

Monocytes play different roles in stimulating T cells in obese diabetic individuals.

Type 2 diabetes (T2D) is a chronic metabolic disorder, which was also found to involve a series of inflammatory disorders, including accumulation of macrophages and T cells in the adipose tissue, increased proinflammatory cytokine production, shifting of macrophage composition toward M1-type, and skewing of peripheral blood T cells toward IL-17 productions. However, these studies were primarily conducted in obese mouse models and/or human subjects with higher BMI, and may not reflect the role of the immune system in non-obese T2D pathogenesis. Here, we examined T cell and monocyte cytokine expression and function in both non-obese and obese T2D patients. We found that IFN-g production by circulating T cells were increased in both non-obese and obese T2D subjects, while IL-17 is only upregulated in obese T2D subjects. Also, circulating monocytes from obese T2D subjects had significantly higher IL-6 production than their counterparts in non-obese T2D subjects. Moreover, monocytes from non-obese T2D subjects could support IFN-g but not IL-17 production in vitro, while that from obese T2D subjects supported both IFN-g and IL-17 production. Together, our results revealed that the role immune system plays in T2D pathogenesis is more complicated than previously thought, and is affected by the person's BMI.

Adjustable Gastric Band Surgery or Medical Management in Patients With Type 2 Diabetes: A Randomized Clinical Trial.

Recommendations for surgical, compared with lifestyle and pharmacologically based, approaches for type 2 diabetes (T2D) management remain controversial. The objective was to compare laparoscopic adjustable gastric band (LAGB) to an intensive medical diabetes and weight management (IMWM) program for T2D. This was designed as a prospective, randomized clinical trial. The setting was two Harvard Medical School-affiliated academic institutions. INTERVENTIONS AND PARTICIPANTS: A 12-month randomized trial comparing LAGB (n = 23) vs IMWM (n = 22) in persons aged 21-65 years with body mass index of 30-45 kg/m(2), T2D diagnosed more than 1 year earlier, and glycated hemoglobin (HbA(1c)) ≥ 6.5% on antihyperglycemic medication(s). The proportion meeting the prespecified primary glycemic endpoint, defined as HbA(1c) < 6.5% and fasting glucose < 7.0 mmol/L at 12 months, on or off medication. After randomization, five participants did not undergo the surgical intervention. Of the 40 initiating intervention (22 males/18 females; age, 51 ± 10 y; body mass index, 36.5 ± 3.7 kg/m(2); diabetes duration, 9 ± 5 y; HbA(1c), 8.2 ± 1.2%; 40% on insulin), the proportion meeting the primary glycemic endpoint was achieved in 33% of the LAGB patients and 23% of the IMWM patients (P = .457). HbA(1c) reduction was similar between groups at both 3 and 12 months (-1.2 ± 0.3 vs -1.0 ± 0.3%; P = .496). Weight loss was similar at 3 months but greater 12 months after LAGB (-13.5 ± 1.7 vs -8.5 ± 1.6 kg; P = .027). Systolic blood pressure reduction was greater after IMWM than LAGB, whereas changes in diastolic blood pressure, lipids, fitness, and cardiovascular risk scores were similar between groups. Patient-reported health status, assessed using the Short Form-36, Impact of Weight on Quality of Life, and Problem Areas in Diabetes, all improved similarly between groups. LAGB and a multidisciplinary IMWM program have similar 1-year benefits on diabetes control, cardiometabolic risk, and patient satisfaction, which should be considered in the context of other factors, such as personal preference, when selecting treatment options with obese T2D patients. Longer duration studies are important to understand emergent differences.

Thyroid Hormones Protect Type 2 Diabetes Obese Patients Against Cardio-Metabolic Risk Factors

Background: Dysfunction of thyroid gland was observed in obese and type 2 diabetes (T2D) patients. The serum level of thyroid stimulating hormone (TSH) is increased in these conditions and inversely correlated with risk factors that related to cardiovascular events. This study aimed to demonstrate the changes in the serum level of thyroid hormones; triiodothyronine (T3) and thyroxin (T4) and TSH in obese T2D patients and to demonstrate the gender-based effect of these hormones against the cardio-metabolic risk factors that existed in those patients. Methods: A total number of 150 obese T2D patients (100 women and 50 men) recruited from Martyr LaylaQasm Center for Diabetes Mellitus in Erbil, Iraq during 2013 were enrolled in this study. The cardio-metabolic risk factors are assessed via measuring body weight, body mass index (BMI), waist circumference, blood pressure, fasting serum glucose and lipid profile, glycosylated hemoglobin and high sensitive C-reactive protein (hsCRP). Serum total T4, T3 and TSH were measured. Results: The serum levels of T4 and T3 attended higher levels in women compared with men while the TSH level is less in women than in men. The significant positive correlations between the TSH and the cardio-metabolic risk factors (except fasting serum glucose and hsCRP) were observed. An inverse pattern was observed with T4 and T3. The coefficient factors of these correlations were higher in women compared with men. Conclusions: It concludes that the thyroid gland function is disturbed in obese T2D patients, and thyroid hormones were significantly and inversely correlated with cardio-metabolic risk factors which were prominently observed in men. J Endocrinol Metab. 2015;5(1-2):179-183 doi: http://dx.doi.org/10.14740/jem274w

Impaired increase of plasma abscisic Acid in response to oral glucose load in type 2 diabetes and in gestational diabetes.

The plant hormone abscisic acid (ABA) is present and active in humans, regulating glucose homeostasis. In normal glucose tolerant (NGT) human subjects, plasma ABA (ABAp) increases 5-fold after an oral glucose load. The aim of this study was to assess the effect of an oral glucose load on ABAp in type 2 diabetes (T2D) subjects. We chose two sub-groups of patients who underwent an oral glucose load for diagnostic purposes: i) 9 treatment-naive T2D subjects, and ii) 9 pregnant women with gestational diabetes (GDM), who underwent the glucose load before and 8–12 weeks after childbirth. Each group was compared with matched NGT controls. The increase of ABAp in response to glucose was found to be abrogated in T2D patients compared to NGT controls. A similar result was observed in the women with GDM compared to pregnant NGT controls; 8–12 weeks after childbirth, however, fasting ABAp and ABAp response to glucose were restored to normal in the GDM subjects, along with glucose tolerance. We also retrospectively compared fasting ABAp before and after bilio-pancreatic diversion (BPD) in obese, but not diabetic subjects, and in obese T2D patients, in which BPD resulted in the resolution of diabetes. Compared to pre-BPD values, basal ABAp significantly increased 1 month after BPD in T2D as well as in NGT subjects, in parallel with a reduction of fasting plasma glucose. These results indicate an impaired hyperglycemia-induced ABAp increase in T2D and in GDM and suggest a beneficial effect of elevated ABAp on glycemic control.

Omental fat from obese and obese diabetic patients dys‐regulates vascular function by NF‐κB, PARP‐1 and interleukin 12‐dependent mechanism (1076.7)

Background: The abdominal adipose omental tissue in obese and obese diabetic patients is a major risk factor for cardiovascular diseases. Here we determined the role of interleukin 12 (IL‐12), NFκB and PARP‐1 in omental tissue‐induced vascular dysfunction in obese, obese type 2 diabetic (T2D) patients, and type 2 diabetic (db‐/db‐) mouse.Methods &amp;amp; results: Mesenteric resistance arteries (MRA) from C57/BL6 and IL‐12 receptor‐/‐ mice were mounted in a wire myograph and incubated with omental fat from obese, obese T2D patients, db‐/db‐ and db‐/db‐p50NFκB‐/‐, db‐/db‐PARP‐1‐/‐ and C57/BL6 mice treated with and without NFκB (DHMQ), PARP‐1 (ABT‐888) inhibitors and IL‐12 receptor antagonist. The endothelium‐dependent relaxation was not affected. However, we observe an increase in phenylephrine‐(PE) and thromboxane‐(U46619)‐induced contraction in MRA incubated with omental fat from obese, obese T2D patients and db‐/db‐ mice. The contraction was potent with omental fat from obese T2D than obese patients. Interestingly, ABT‐888, DHMQ, IL‐12 receptor antagonist and MRA from IL‐12 receptor‐/‐ significantly reduced the exacerbated PE and thromboxane‐induced contraction in MRA incubated with omental fat from obese, obese T2D patients or db‐/db‐. Importantly, PE and thromboxane‐induced contraction was significantly reduced when MRA from db‐/db‐p50NFκB‐/‐ or db‐/db‐PARP‐1‐/‐ double knockout mice were incubated with omental fat from obese, obese T2D patients and db‐/db‐ mice. These results were associated with augmented NFkB and PARP‐1 activity and IL‐12 content in omental fat from obese, obese T2D patients and db‐/db‐ mice compared to control. IL‐12 content was significantly reduced in omental fat incubated with NFkB and PARP‐1 inhibitors.Conclusion: The present study provide evidence that adipose omental tissue in obese, obese T2D patients and T2D mouse impairs vascular function by IL‐12, NFκB and PARP‐1‐dependent mechanisms

Long-Term Effects of Bariatric Surgery on Meal Disposal and β-Cell Function in Diabetic and Nondiabetic Patients

Gastric bypass surgery leads to marked improvements in glucose tolerance and insulin sensitivity in obese type 2 diabetes (T2D); the impact on glucose fluxes in response to a physiological stimulus, such as a mixed meal test (MTT), has not been determined. We administered an MTT to 12 obese T2D patients and 15 obese nondiabetic (ND) subjects before and 1 year after surgery (10 T2D and 11 ND) using the double-tracer technique and modeling of β-cell function. In both groups postsurgery, tracer-derived appearance of oral glucose was biphasic, a rapid increase followed by a sharp drop, a pattern that was mirrored by postprandial glucose levels and insulin secretion. In diabetic patients, surgery lowered fasting and postprandial glucose levels, peripheral insulin sensitivity increased in proportion to weight loss (∼30%), and β-cell glucose sensitivity doubled but did not normalize (compared with 21 nonsurgical obese and lean controls). Endogenous glucose production, however, was less suppressed during the MMT as the combined result of a relative hyperglucagonemia and the rapid fall in plasma glucose and insulin levels. We conclude that in T2D, bypass surgery changes the postprandial response to a dumping-like pattern and improves glucose tolerance, β-cell function, and peripheral insulin sensitivity but worsens endogenous glucose output in response to a physiological stimulus.

Genetic association of adrenergic receptor alpha 2A with obesity and type 2 diabetes

The sympathetic nervous system (SNS) is linked to glucose, lipid, and protein metabolism. The α2A -adrenergic receptor (ADRA2A) is involved in the SNS and mediates inhibition of insulin secretion and lipolysis. The association of ADRA2A single-nucleotide polymorphisms (SNPs) with obesity and/or type 2 diabetes (T2D) was investigated. Genotyping was performed in a case-control study of 1,177 Swedish individuals, including lean and obese subjects with normal glucose tolerance (NGT) and T2D patients. ADRA2A mRNA expression was measured in pancreatic islets isolated from T2D patients and nondiabetic subjects. SNP rs553668 was associated with T2D in men (odds ratio [OR] = 1.47; 95% confidence interval [CI] = 1.08-2.01; P = 0.015) but this association was lost after adjusting for age and for body mass index (BMI). Associations were also detected when comparing obese NGT and lean NGT subjects (OR = 1.49; 95% CI = 1.07-2.07; P = 0.017), and in obese (OR = 1.62; 95% CI = 1.06-2.49; P = 0.026), but not in lean T2D. In women, multiple logistic regression regarding SNP rs521674 demonstrated an increased OR of 7.61 (95% CI = 1.70-34.17; P = 0.008) for T2D when including age as a covariant. Correcting for BMI removed the significant association. When age was included in the model, association also found when obese T2D patients were compared with lean NGT subjects (P = 0.041). ADRA2A mRNA expression in human pancreatic islets was detectable, but with no statistically significant difference between the diabetic and the control groups. ADRA2A genetic polymorphisms are mainly associated with obesity and possibly with T2D in a Swedish population.

Comparison of Lipid Profile in Type-2 Obese Diabetics and Obese Non-diabetic Individuals. A hospital Based Study from Western Nepal

Type-2 diabetes mellitus is an independent risk factor for coronary artery disease and risk of coronary disease is three to four fold increased in patients with diabetes compared with non-diabetic population and 60-80% 0f type-2 diabetics are obese. This study was conducted in Nepalgunj Teaching Hospital, Kohalpur, Banke, Nepal, between 1st March, 2011 and 28th February, 2012. A total of 150 samples were taken to assess the lipid profile in type-2 diabetic patients associated with obesity and 25 obese controls for their lipid profile. Venous blood samples were taken from all the subjects in the morning after fasting overnight. Exclusion criteria included pregnancy, chronic infectious disease, heart failure; renal failure and drug allergy were confirmed from the subject's personal physician report and a detailed history. The data was analyzed using Excel 2003, R 2.8.0 Statistical Package for the Social Sciences (SPSS) for Windows Version 16.0 (SPSS Inc; Chicago, IL, USA) and the EPI Info 3.5.1 Windows Version. The mean ± SD age of diabetic patients with obesity was 53.76± 6.23 while the mean ± SD age of control was 49.61 ± 4.8. Out of 150 patients 105 (70%) were males and 45 (30%) were females. Among control subjects 16 (64%) were males and 9 (36%) were females. Obese type-2 diabetic patients when compared to obese control subjects showed statistically significant increase in the levels of serum total cholesterol (p < 0.001), serum triglycerides (p < 0.001), serum LDL-cholesterol (p < 0.001) while serum HDL-cholesterol levels did not show statistically significant difference in the two group (p > 0.05). This study showed obese diabetic individuals have dyslipidemia and more prone to develop cardiovascular diseases.

P 14: Hypertriglyceridemic waist phenotype in type 2 diabetes: association with higher hs-CRP and lower antioxidative enzyme activity

Background and aim It was previously suggested that hypertriglyceridemic waist (HTgW) phenotype (waist girth ≥90 cm in men and ≥85 cm in women, and triglyceride (Tg) levels ≥2.0 mmol/l) could identify visceral obesity and higher risk for atherosclerosis, but the relationship between HTgW phenotype and different atherosclerosis risk factors has not yet been elucidated. The aim of this study was to analize (a) hs-CRP levels, (b) lipid levels and (c) antioxidant enzyme glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities in the following groups of subjects: 30 patients with type 2 diabetes (T2D) and HTgW (group A), 24 T2D patients with abdominal obesity (higher waist) and normal Tg (group B) and 20 non obese T2D patients without HTgW (group C). Methods CRP levels were detected by Elisa method, GSH-Px and SOD activity were detected by spectrophotometry, total cholesterol (Ch), HDL-Ch, LDL-Ch and Tg levels by enzymatic methods and the insulin resistance (IR) was assessed by using HOMA-IR (calculated from basal insulin levels determined by RIA and fasting glucose levels determined by glucosooxidase method). Results We found significantly higher hs-CRP level in group A compared to group B (6,97+/-2,01 vs 4,72+/-2,01 mg/l; p Conclusions Our results signify that presence of HTgW phenotype in T2D, as a marker of visceral obesity, is strongly associated with marked atherosclerosis risk profile, especially at the level of inflammation, reverse cholesterol metabolism and antioxidative enzyme activity. The results also suggest that in this phenotype detected higher IR might be exerting its atherogenic effect partly on the level of the changes in antioxidative defence.