Obese Type 2 Diabetes Mellitus Subjects Research Articles

The Role of Pro-Inflammatory Chemokines CCL-1, 2, 4, and 5 in the Etiopathogenesis of Type 2 Diabetes Mellitus in Subjects from the Asir Region of Saudi Arabia: Correlation with Different Degrees of Obesity.

Type 2 diabetes mellitus (T2DM) is becoming a major global health concern, especially in developing nations. The high prevalence of obesity and related diabetes cases are attributed to rapid economic progress, physical inactivity, the consumption of high-calorie foods, and changing lifestyles. We investigated the roles of pro-inflammatory chemokines CCL1, 2, 4, and 5 in T2DM with varying levels of obesity in the Asir region of Saudi Arabia. In total, 170 confirmed T2DM subjects and a normal control group were enrolled. Demographic data, serum levels of CCL-1, 2, 4, and 5, and biochemical indices were assessed in the subjects and control groups by standard procedures. T2DM subjects were divided into four groups: A (normal body weight), B (overweight), C (obese), and D (highly obese). We observed that male and female control subjects had similar mean serum concentrations of pro-inflammatory chemokines CCL-1, 2, 4, and 5. T2DM subjects in all the four groups showed significantly higher levels of all the four chemokines compared to the controls, regardless of gender. In T2DM subjects with obesity and severe obesity, the rise was most significant. There was a progressive rise in the concentrations of CCL-1, 2, and 4 in T2DM subjects with increasing BMI. Serum CCL5 levels increased significantly in all T2DM subject groups. The increase in CCL5 was more predominant in normal-weight people, compared to overweight and obese T2DM subjects. Male and female control subjects had similar serum levels of pro-inflammatory chemokines CCL-1, 2, 4, and 5. The progressive rise in blood concentrations of three pro-inflammatory chemokines CCL-1, 2, and 4 in T2DM subjects with increasing BMI supports the idea that dyslipidemia and obesity contribute to chronic inflammation and insulin resistance. Serum CCL5 levels increased significantly in all T2DM subject groups. The selective and more pronounced increase in CCL5 in the T2DM group with normal BMI, compared to subjects with varying degrees of obesity, was rather surprising. Further research is needed to determine if CCL5 underexpression in overweight and obese T2DM subjects is due to some unexplained counterbalancing processes.

Taste dyfunction in obese type 2 diabetic individuals

Obesity is a well-known risk factor for many diseases. It is also known to enhance complications of many diseases eg. Type 2 Diabetes mellitus (T2DM). This study was done to assess the gustatory functions in obese T2DM individuals. This study was done to assess the gustatory functions in obese T2DM subjects and compare the same with lean T2DM individuals. A comparative study with a sample size of 40 was conducted. Patients aged 25 to 50 years with T2DM < 5 years duration and HBA1C ≤ 7 were divided into 2 groups, Group I- with normal weight (BMI of 18.5 to <25) and Group II with grade 1 obesity (BMI of 30 to < 35). Triple Drop Test was done to evaluate gustatory functions. Scoring from “5” to “1” was done on the identification of different concentrations of tastants. Taste scores for sweet, salty, sour, and bitter tastants were lesser in obese diabetics as compared to the lean T2DM subjects. This was statistically significant (p < 0.05) Conclusion: Taste impairment is observed in obese diabetic subjects. This could be an indication of early central diabetic neuropathy. Hypogeusia may cause an increased preference for sweet-tasting or salty foods thus imposing greater health risks, increasing obesity, and negatively affecting the quality of life.

OXIDATIVE STRESS LEVELS ARE INCREASED IN TYPE 2 DIABETES MELLITUS AND OBESITY

Objective: The relationship between obesity, type 2 diabetes mellitus (T2DM) and oxidative stress (OS) is complex and insufficiently studied. Chronic hyperglycemia causes endothelial damage by increasing reactive oxygen species (ROS) production and decreasing the activity of antioxidant enzymes, explaining why OS is a main contributor in T2DM pathogenesis. The adipose tissue is also a source of ROS via low-grade chronic inflammation and deregulation of adipokine secretion. Thus, we aimed to evaluate OS levels in obese T2DM subjects and obese non-T2DM subjects vs. controls. Design and method: OS was measured in 20 T2DM obese patients (mean age 64.85 ± 7.74 years), 20 obese non-T2DM patients (mean age 61.30 ± 10.59 years) and 20 non-obese non-T2DM controls (mean age 64.10 ± 2.26 years). ROS were evaluated via the Free Oxygen Radical Testing (FORT; normal range: < = 2.3 mmol/L H2O2) assay. The total antioxidant capacity was measured by the Free Oxygen Radical Defense (FORD; normal range: 1.07 – 1.53 mmol/L Trolox) test. Results: T2DM obese subjects registered higher FORT (3.33 ± 0.30 vs. 3.10 ± 0.34; p = 0.017) and lower FORD (0.60 ± 0.10 vs. 0.71 ± 0.15; p = 0.008) values compared to their obese non-T2DM counterparts. Both obese T2DM subjects and obese non-T2DM subjects depicted higher FORT and lower FORD values vs. controls (p < 0.001) (Table 1). In obese T2DM subjects, FORT values correlated positively with BMI, LDL-cholesterol, total cholesterol, triglycerides, uric acid and HDL/cholesterol value and negatively with age. FORD values evolved oppositely (Table 2).Conclusions: Obese T2DM subjects recorded higher FORT and lower FORD values vs. obese non-T2DM. In both obese T2DM and obese non-T2DM subjects, OS levels were higher vs. controls. In obese T2DM subjects, ROS levels correlated positively with lipid values, BMI, uric acid and, surprisingly, negatively with age. The total antioxidant capacity evolved oppositely. The negative correlation between age and ROS levels and the positive correlation between FORD and age are paradoxical since the ageing process is associated with higher ROS and lower antioxidant values.

Serum fetuin-A levels in obese and non-obese subjects with and without type 2 diabetes mellitus

BackgroundHigher fetuin-A expression is linked to both obesity and type 2 diabetes mellitus (T2DM), However, studies in non-obese patients with T2DM are scarce. Methods345 newly diagnosed T2DM patients and 300 subjects with normal glucose tolerance (NGT) were divided into obese and non-obese subgroups, respectively. Serum fetuin-A and adiponectin levels and related parameters were measured. ResultsT2DM patients with obesity had higher fetuin-A levels compared with non-obese patients and obese NGT subjects (p<0.001). Significant correlations were observed between fetuin-A and most metabolic parameters in obese NGT and T2DM subjects, but which was not in non-obese patients with T2DM. The independent associations were found between fetuin-A and free fatty acids, HOMA-IR, C-reactive protein and adiponectin only in obese NGT and T2DM subjects (all p<0.05). The adjusted odds ratios for obesity were increased with increasing quartile of fetuin-A in both T2DM and NGT subjects in logistic regression models (p for trend<0.001), but which was more significant in T2DM patients. ConclusionHigher serum fetuin-A levels in obese T2DM patients compared with non-obese patients and obese NGT subjects supports the hypothesis that fetuin-A may be as a bridge connecting obesity and obesity-related T2DM.

Evaluation of Leptin as a Marker of Insulin Resistance in Type 2 Diabetes Mellitus.

Background:Type 2 diabetes mellitus (T2DM) is a leading cause of mortality and morbidity worldwide, whose incidence is rapidly increasing in India. T2DM is caused by varying degrees of insulin resistance (IR) and relative insulin deficiency. Leptin, an adipokine with the primary function of regulating energy balance, is found to mediate insulin secretion and sensitivity in peripheral tissues. Hence, we aimed to determine the role of leptin in the development of IR in newly diagnosed T2DM patients.Aim:This study aims to compare the leptin levels and homeostatic model assessment-IR (HOMA-IR) levels in the study population.Material and Methods:The study included a total of sixty patients newly diagnosed with T2DM. Their fasting blood samples were collected to estimate the glucose, insulin, and leptin levels. IR was calculated using HOMA-IR formula. Statistical analysis was done by Pearson's correlation, Spearman's correlation, and One-sample Wilcoxon Signed Rank test.Results:Leptin and HOMA-IR levels were significantly high in T2DM patients (P < 0.001) when compared with reference values. Body mass index showed a significant positive correlations with insulin (r = 0.40, P < 0.01), HOMA-IR (r = 0.37, P < 0.01), and leptin levels (r = 0.90, P < 0.01). Leptin levels showed significant positive correlations with plasma insulin (r = 0.35, P < 0.01) and HOMA-IR levels (r = 0.31, P < 0.05). The correlation between leptin and HOMA-IR levels was more pronounced and significant among the obese T2DM subjects (r = 0.82, P = 0.01).Conclusion:Hyperleptinemia reflecting leptin resistance plays an important role in the development of IR in obeseT2DM patients, making leptin a possible biomarker for the same.

Identification of a definite diabetic cardiomyopathy in type 2 diabetes by comprehensive echocardiographic evaluation: A cross‐sectional comparison with non‐diabetic weight‐matched controls

Subclinical left ventricular (LV) dysfunction is prevalent in type 2 diabetes (T2DM). As obesity has been proposed as one causal factor in the disease process, this could bias the reported prevalences. We wanted to characterize echocardiographic LV dysfunction in obese T2DM subjects as compared to non-diabetic obese controls. One hundred patients with T2DM without clinical signs of heart failure (29% females, mean ± SD age 58.4 ± 10.5 years, body mass index (BMI) 30.1 ± 5.5 kg/m(2), blood pressure (BP) 141 ± 18/83 ± 9 mmHg) and 100 non-diabetic controls (29% females) matched for age (58.6 ± 10.5 years), BMI (29.8 ± 4.0 kg/m(2) and systolic BP (140 ± 14 mmHg) underwent echocardiography and color tissue Doppler imaging (TDI). Diastolic function was evaluated with conventional Doppler recordings and early (e') and late (a') myocardial velocities. The ratio between early transmitral filling (E) and the corresponding myocardial tissue velocity (e') served as an index of LV filling pressure. T2DM patients had more concentric hypertrophy with a relative wall thickness of 0.42 ± 0.07 vs controls 0.38 ± 0.07, P < 0.001. The T2DM group had signs of diastolic dysfunction with lower E/A ratio (0.91 ± 0.27 vs. 1.12 ± 0.38, P < 0.001), deceleration time (195 ± 49 vs 242 ± 72 ms, P < 0.001), e' (5.7 ± 2.0 vs. 6.6 ± 1.8 cm/s, P = 0.001), and a' (6.5 ± 2.0 vs. 7.6 ± 1.5 cm/s, P < 0.001) compared to the controls, and higher E/e' (13.3 ± 4.7 vs. 11.1 ± 3.5, P < 0.001). Thus, there were indications of pseudo normalization and increased filling pressure in the T2DM group, whereas the controls had evidence for relaxation abnormalities without elevated filling pressure. Compared to a non-diabetic obese group, more advanced subclinical impairment of diastolic function was seen in T2DM.

Betatrophin Acts as a Diagnostic Biomarker in Type 2 Diabetes Mellitus and Is Negatively Associated with HDL-Cholesterol.

Objective. By assessing its circulating concentrations in type 2 diabetes mellitus (T2DM) patients, we aimed to explore the associations of betatrophin with various metabolic parameters and evaluate its diagnostic value in T2DM. Methods. A total of 58 non-diabetes-mellitus (NDM) subjects and 73 age- and sex-matched newly diagnosed T2DM patients were enrolled. Correlation analyses between circulating betatrophin levels and multiple metabolic parameters were performed. Receiver operating characteristic (ROC) curve analysis was used to assess the diagnostic value of betatrophin concentration in T2DM. Results. Circulating betatrophin levels were approximately 1.8 times higher in T2DM patients than in NDM individuals (median 747.12 versus 407.41 pg/mL, P < 0.001). Correlation analysis showed that betatrophin was negatively associated with high-density lipoprotein cholesterol (HDL-C) levels in all subjects. ROC curve analysis identified betatrophin as a potent diagnostic biomarker for T2DM. The optimal cut-off point of betatrophin concentration for predicting T2DM was 501.23 pg/mL. Conclusions. Serum betatrophin levels were markedly increased in newly diagnosed T2DM patients and further elevated in obese T2DM subjects. Betatrophin was negatively correlated with HDL-C levels. Our findings indicate that betatrophin could be a potent diagnostic biomarker for T2DM.

Present and future association between obesity and hypogonadism in Italian male

Obesity prevalence is increasing worldwide and it is nowadays considered a real public health problem. Obesity is associated with co-morbidities like cardiovascular diseases (CVD) and type 2 diabetes mellitus (T2DM), furthermore visceral obesity can be related to low testosterone (T) plasma levels. The link between obesity and hypogonadism (HG) is complex and not completely clarified. Current guidelines suggest that screening for HG should be done in subjects with obesity and T2DM. The aim of this evaluation is to assess the estimated actual and future prevalence of obesity and related co-morbidities, in particular HG, in the Italian general population. The Strategyst Consulting Inc. recently completed an epidemiology forecast model for several countries, looking at HG and CV/Metabolic Disease, based on National Health and Nutrition Examination Survey (NHANES) data collected between 1999-2010. Data from NHANES survey were used to evaluate the Italian estimated prevalence of obesity and HG. Results show that obesity estimated prevalence will increase in 2030 also in Italy. In addition, also the prevalence of obese CVD and T2DM subjects will increase too. Even Italian HG prevalence is estimated to increase in the next two decades, irrespective of T threshold considered (< 8, 10 and 12 nmol/L). In obese CVD subjects the relative risk (RR) of developing HG (T < 8 nmol/L) is four times greater than in not-CVD obese subjects (RR = 4.1, 3.1 and 1.9 accordingly to the aforementioned T thresholds for defining HG). Accordingly, the estimated percentage of hypogonadal obese CVD and T2DM subjects will rise in 2030. The Strategyst epidemiology forecast model has allowed to assess the current and future prevalence of obesity and its relative co-morbidities like HG in Italy. Data emerged from this evaluation suggest that obesity and HG prevalence will increase in Italian population and confirm the complex link between adipose tissue and male T levels.

Autonomic nervous system activity in diabetic and healthy obese female subjects and the effect of distinct weight loss strategies

Obesity and type 2 diabetes mellitus (T2DM) are reported to be associated with relative overactivity of the sympathetic nervous system (SNS), which is reversible by weight loss. However, direct effects of weight loss by calorie restriction vs Roux-en-Y gastric bypass (RYGB) on SNS overactivity were not studied in parallel. This study compared the effects of RYGB vs restrictive weight loss in obese patients with normal glucose tolerance (NGT) and with T2DM on SNS function as measured by heart rate variability (HRV). Lean (n=12), obese NGT (n=27) and T2DM (n=27) subjects were included in this study. Weight reduction in NGT subjects was achieved by gastric banding (GB) or RYGB and in T2DM subjects by RYGB or high-protein very-low-calorie diet (VLCD). HRV analysis was performed and blood samples were taken at baseline, 3 weeks and 3 months after intervention. At baseline, T2DM subjects showed SNS overactivity and NGT subjects showed similar, but non-significant, findings when compared with lean controls. Weight loss after 3 weeks was comparable in all treatment groups, whereas after 3 months, weight loss was most in VLCD and RYGB subjects. RYGB and VLCD treatment reduced SNS activity within 3 weeks in T2DM patients. After 3 months, restoration to normal autonomic nervous system activity was evident for all groups, except for the NGT-GB group. We can conclude that SNS overactivity is more pronounced in obese T2DM subjects when compared with NGT subjects. Reduction of SNS overactivity coincides with weight loss with the time-course of reduction dependent on the type of intervention. Surgery or caloric restriction may transiently induce SNS overactivity but do not prevent a direct restoration of sympathovagal balance.

Ghrelin suppression is associated with weight loss and insulin action following gastric bypass surgery at 12 months in obese adults with type 2 diabetes

Roux-en-Y gastric bypass (RYGB) surgery reverses type 2 diabetes mellitus (T2DM) in approximately 80% of patients. Ghrelin regulates glucose homeostasis, but its role in T2DM remission after RYGB surgery is unclear. Nine obese T2DM subjects underwent a mixed meal tolerance test before and at 1 and 12 months after RYGB surgery. Changes in ghrelin, body weight, glucagon-like polypeptide-1 (GLP-1, glucose tolerance and insulin sensitivity (IS) were measured. At 1 month, body weight, glycaemia and IS were improved, while ghrelin concentrations were reduced (p < 0.05). After 12 months, body weight and fasting glucose were reduced (30 and 16%, respectively; p < 0.05) and IS was enhanced (threefold; p < 0.05). Ghrelin suppression improved by 32% at 12 months (p < 0.05), and this was associated with weight loss (r = 0.72, p = 0.03), enhanced IS (r = -0.78, p = 0.01) and peak postprandial GLP-1 (r = -0.73, p = 0.03). These data suggest that postprandial ghrelin suppression may be part of the mechanism that contributes to diabetes remission after RYGB surgery.

Effects of Sleeve Gastrectomy Versus Gastric Bypass on Type 2 Diabetes Mellitus Remission in Obese Patients

AbstractObjectives: To determine and compare the efficacy of two weight-reducing surgicalinterventions, gastric bypass (GBP) and sleeve gastrectomy (SG), in inducingremission/improvement of type 2 diabetes mellitus (T2DM). Materials and Methods:Data were collected from 162 obese T2DM subjects who underwent SG (96) or GBP(66) between 2009 and 2011. The following parameters were recorded: body massindex, waist-hip-ratio, blood pressure, fasting plasma glucose, HbA1c, lipid profile,hypoglycemic drugs used. Results: Remission of T2DM was achieved in 83% ofpatients who underwent SG and in 81% of patients who underwent GBP. For bothprocedures, T2DM remission rate was higher for patients with a shorter duration ofT2DM, with better preoperative glycemic control and for those not requiringpharmacological agents before surgery. Conclusions: SG and GBP are effective ininducing T2DM remission in obese patients. The clinical features of T2DM areimportant predictors for the remission of the disease after bariatric surgery.

Comparable early changes in gastrointestinal hormones after sleeve gastrectomy and Roux-En-Y gastric bypass surgery for morbidly obese type 2 diabetic subjects

Sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGBP) are associated with similar type 2 diabetes mellitus (T2DM) resolution rates for morbidly obese subjects. However, the mechanisms underlying the resolution of T2DM after SG have not been clarified to date. This study aimed to compare the early changes in gastrointestinal hormones involved in insulin and glucagon secretion in morbidly obese T2DM subjects undergoing SG or RYGBP. This prospective study investigated 12 subjects with T2DM who had undergone SG (n = 6) or RYGBP (n = 6). Five body mass index (BMI)-matched obese non-diabetic subjects and five BMI-matched obese diabetic subjects served as control subjects. Glucose, insulin, glucagon, glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and GLP-2 were determined after a standardized mixed liquid meal before surgery and 6 weeks afterward. After 6 weeks, five of the six subjects in each surgical group presented with T2DM remission, although the area under the curve (AUC)0–120 of glucose was greater than that of the non-diabetic control subjects (P < 0.01). Postsurgically, the indices of insulin and glucagon secretion were comparable between the two surgical groups. The AUC0–120 of GLP-1 (P < 0.05) and GLP-2 (P < 0.05) was significantly and comparably enlarged after SG and RYGB. The postsurgical GIP response was significantly associated with the glucagon response throughout the meal test (ρ = 0.747; P < 0.01). The data show that in a cohort of morbidly obese T2DM subjects, SG and RYGBP are associated with an early improvement in glucose tolerance, similar changes in insulin and glucagon secretion, and a similar GLP-1, GIP, and GLP-2 response to a standardized mixed liquid meal.

Substance P is Associated with the Development of Obesity, Chronic Inflammation and Type 2 Diabetes Mellitus

Substance P (SP) is an important neurotransmitter and is an important pathogenic factor in obesity. However, the relationships between the inflammatory cytokines interleukin-6 (IL-6), C reactive protein (CRP) and SP with obesity and type 2 diabetes mellitus (T2DM) are poorly understood. We investigated the associations between SP, IL-6 and CRP with obesity and T2DM. The subjects comprised patients who underwent physical examinations at the First Affiliated Hospital of Harbin Medical University between January 2006 and December 2008. Overall, 156 subjects participated in this study, including 63 obese (BMI >25 kg/m²) subjects with T2DM, and 58 obese and 35 lean subjects without T2DM. Patient characteristics were collected from a health questionnaire form. Anthropometric measurements and fasting blood samples were assessed. SP, CRP, IL-6 and HOMA-IR were converted into log values. SP, IL-6, CRP and HOMA-IR were significantly higher ( P<0.05) in obese T2DM subjects compared with obese and lean subjects without T2DM. All 3 parameters were significantly associated with other risk factors for diabetes, including BMI, blood pressure, plasma glucose and high-density lipoprotein levels. After adjusting for age, SP was significantly and positively correlated with BMI and logHOMA-IR ( P≤0.05); correlation coefficients were higher in obese T2DM subjects than in lean or obese subjects without T2DM. High levels of SP and IL-6 were significantly associated with obesity and risk factors for T2DM. Associations were of greatest in obese T2DM subjects. Obesity and T2DM show additive effects on the association between SP and BMI or logHOMA-IR.

β‐Cell Function Improvement After Biliopancreatic Diversion in Subjects With Type 2 Diabetes and Morbid Obesity

In subjects with obesity and type 2 diabetes mellitus (T2DM), biliopancreatic diversion (BPD) improves glucose stimulated insulin secretion, whereas the effects on other secretion mechanisms are still unknown. Our objective was to evaluate the early effects of BPD on nonglucose-stimulated insulin secretion. In 16 morbid obese subjects (9 with T2DM and 7 with normal fasting glucose (NFG)), we measured insulin secretion after glucose-dependent arginine stimulation test and after intravenous glucose tolerance test (IVGTT) before and 1 month after BPD. After surgery the mean weight lost was 13% in both groups. The acute insulin response during IVGTT was improved in T2DM after BDP (from 55 +/- 10 to 277 +/- 91 pmol/l, P = 0.03). A reduction of insulin response to arginine was observed in NFG, whereas opposite was found in T2DM. In particular, acute insulin response to arginine at basal glucose concentrations (AIR(basal)) was reduced but insulin response at 14 mmol/l of plasma glucose (AIR(14)) was increased. Therefore, after BPD any statistical difference in AIR(14) between NFG and T2DM disappeared (1,032 +/- 123 for NFG and 665 +/- 236 pmol/l for T2DM, P = ns). The same was observed for Slope(AIR), a measure of glucose potentiation, reduced in T2DM before BPD but increased after surgery, when no statistically significant difference resulted compared with NFG (Slope(AIR) after BPD: 78 +/- 11 in NFG and 56 +/- 18 pmol/l in T2DM, P = ns). In conclusion, in obese T2DM subjects 1 month after BPD we observed a great improvement of both glucose- and nonglucose-stimulated insulin secretions. The mechanisms by which BDP improve insulin secretion are still unknown.

Gastric Electrical Stimulation with the TANTALUS® System in Obese Type 2 Diabetes Patients: Effect on Weight and Glycemic Control

The TANTALUS System is an investigational device that consists of an implantable pulse generator connected to gastric electrodes. The system is designed to automatically detect when eating starts and only then deliver sessions of gastric electrical stimulation (GES) with electrical pulses that are synchronized to the intrinsic antral slow waves. We report the effect of this type of GES on weight loss and glucose control in overweight/obese subjects with type 2 diabetes mellitus (T2DM). This study was conducted under a Food and Drug Administration/Institutional Review Board-approved investigational device exemption. Fourteen obese T2DM subjects on oral antidiabetes medication were enrolled and implanted laparoscopically with the TANTALUS System (body mass index 39 +/- 1 kg/m(2), hemoglobin A1c [HbA1c] 8.5 +/- 0.2%).Gastric electrical stimulation was initiated four weeks after implantation. Weight, HbA1c, fasting blood glucose, blood pressure, and lipid levels were assessed during the study period. Eleven subjects reached the 6-month treatment period endpoint. Gastric electrical stimulation was well tolerated by all subjects. In those patients completing 6 months of therapy, HbA1c was reduced significantly from 8.5 +/- 0.7% to 7.6 +/- 1%, p < .01. Weight was also significantly reduced from 107.7 +/- 21.1 to 102.4 +/- 20.5 kg, p < .01. The improvement in glucose control did not correlate with weight loss (R(2) = 0.05, p = .44). A significant improvement was noted in blood pressure, triglycerides, and cholesterol (low-density lipoprotein only). Short-term therapy with the TANTALUS System improves glucose control, induces weight loss, and improves blood pressure and lipids in obese T2DM subjects on oral antidiabetes therapy.

Improvement in glycemic control by gastric electrical stimulation (TANTALUSTM) in overweight subjects with type 2 diabetes

The TANTALUS system (MetaCure Ltd.) is a minimally invasive implantable gastric stimulation modality that does not exhibit malabsorptive or restrictive characteristics. The device applies gastric contractility modulation (GCM) signals to the stomach antrum. The signals are delivered in synchronization to the native electrical activity of the stomach during meals. Retrospective analysis of previous studies indicated that type 2 diabetes mellitus (T2DM) subjects on oral medication with hemoglobin A1c (HbA1c) between 7.5% and 9.5% are the population with most potential benefit from the treatment. The current study includes subjects enrolled prospectively within that range of HbA1c. To prospectively investigate the potential effect of the TANTALUS system on glycemic control and weight in overweight subjects with T2DM. In this European multicenter, open-label study, 13 T2DM obese (6 male, 7 female, BMI 37.2 +/- 1.0 kg/m(2), range 30.4-44.0 kg/m(2)) subjects treated with oral antidiabetic medications but with poor glycemic control (HbA1c > or = 7%, range 7.3-9.5%) were implanted laparoscopically with the TANTALUS system. Thirteen subjects that had completed 3 months of treatment showed a significant reduction in HbA1c from 8.0 +/- 0.2% to 6.9 +/- 0.1% (p < 0.05), whereas fasting blood glucose decreased from 175 +/- 6 mg/dL to 127 +/- 8 mg/dL (p < 0.05). The glycemic improvement was accompanied by reduction in weight from 104.4 +/- 4.4 kg to 99.7 +/- 4.8 kg, and in waist circumference from 122.3 +/- 3.2 cm to 117.0 +/- 3.0 cm. Interim results with the TANTALUS system suggest that this stimulation regime can potentially improve glucose levels and induce moderate weight loss in obese T2DM subjects on oral antidiabetic therapy with poor glycemic control. Further evaluation is required to determine whether this effect is due to induced weight loss and/or due to direct signal-dependent mechanisms.

Influence of Morbid Obesity and Insulin Resistance on Gene Expression Levels of AQP7 in Visceral Adipose Tissue and AQP9 in Liver

Glycerol production and its efflux from adipocytes to the liver are key to modulate lipid and glucose homeostasis. Aquaporin 7 (AQP7) is an aquaglyceroporin that acts as the adipose glycerol channel, whereas aquaporin 9 (AQP9) is the specific channel operating in the liver. The aim of the present work was to evaluate the effect of obesity and type 2 diabetes mellitus (T2DM) on gene expression levels of AQP7 in visceral adipose tissue (VAT) and AQP9 in liver. VAT and liver biopsies obtained from 20 women were used in the study. Patients were classified as lean or obese with the last group being further subclassified as normoglycemic (NG), patients with impaired glucose tolerance (IGT), or with T2DM. Anthropometric measurements as well as circulating metabolites, hormones, and adipokines were determined. Real-time polymerase chain reaction analyses were performed to quantify transcript levels of AQP7 in VAT and AQP9 in the liver. Gene expression levels of AQP7 in VAT showed a tendency toward an increase (P = 0.065) in obese patients (both NG and T2DM) compared to lean subjects. AQP9 showed a significant downregulation in the hepatic biopsies obtained from obese T2DM patients compared to obese NG and IGT patients (P = 0.028). The tendency toward an elevation of mRNA expression of VAT AQP7 in obesity together with the decreased hepatic AQP9 expression observed in obese T2DM subjects suggests a potential role in facilitating glycerol release from adipose tissue and reducing glycerol entry into hepatocytes in obesity and T2DM, respectively.

Proinflammatory Cytokines in Obesity: Impact of Type 2 Diabetes Mellitus and Gastric Bypass

Obesity and obesity-associated type 2 diabetes mellitus (T2DM) are frequently related to a low-grade chronic inflammatory state, which increases the risk of developing cardiovascular diseases. The aim of the present work was to evaluate the effect of obesity and T2DM on the concentrations of pro-inflammatory factors and to study the effect of weight loss after Roux-en-Y gastric bypass (RYGBP). Plasma concentrations of monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-alpha), serum amyloid A (SAA) and sialic acid (SA) were measured in 25 female volunteers. The concentrations of these cytokines were determined in 14 female obese patients before and after weight loss following RYGBP. Additionally, visceral adipose tissue (VAT) obtained from 15 females was used to quantify expression levels of MCP-1 and CD68 by Real-Time PCR. Both obese normoglycemic (NG) and T2DM groups exhibited significantly higher MCP-1 (P < 0.05), TNF-alpha (P < 0.01), SAA (P < 0.05) and SA (P < 0.05) concentrations, compared to the lean group. No differences were found between obese NG and obese T2DM subjects. A significant positive correlation was found between body fat percentage (BF) and all inflammatory markers (P < 0.05) studied. MCP-1 expression levels in VAT were upregulated in obese NG (P = 0.008) and obese T2DM (P = 0.032) patients compared to lean subjects, but no additional detrimental effect of T2DM was observed between both obese groups. After weight loss, SAA (P < 0.001) and SA (P < 0.05) concentrations diminished, whereas circulating levels of MCP-1 showed a tendency to decrease (P = 0.093) and TNF-alpha did not change. The present findings suggest that elevated pro-inflammatory cytokine levels found in obese patients relate mainly to obesity rather than to T2DM. Moreover, surgery-induced weight loss reduces circulating concentrations of key pro-inflammatory factors, which contribute to the improvement in the cardiovascular co-morbidity following excess weight loss.

Short-term Effects of Sleeve Gastrectomy on Type 2 Diabetes Mellitus in Severely Obese Subjects

Data on the effectiveness of sleeve gastrectomy (SG) in improving or resolving type 2 diabetes mellitus (T2DM) are scarce. A 4-month prospective study was conducted on the changes in glucose homeostasis in 35 severely obese T2DM subjects undergoing laparoscopic SG (LSG) and 50 subjects undergoing laparoscopic Roux-en-Y gastric bypass (LRYGBP), matched for DM duration, type of DM treatment, and glycemic control. At 4-months after surgery, LSG and LRYGBP operated subjects lost a similar amount of weight (respectively, 20.6 +/- 0.7% and 21.0 +/- 0.6%). T2DM had resolved respectively in 51.4% and 62.0% of the LSG and LRYGBP operated subjects (P = 0.332). A shorter preoperative DM duration (P < 0.05), a preoperative DM treatment not including pharmacological agents, and a better pre-surgical fasting plasma glucose (P < 0.01) or HbAlc (P < 0.01), were significantly associated with a better type 2 DM outcome in both surgical groups. Our data show that LSG and LRYGBP result in a similar rate of type 2 DM resolution at 4-months after surgery. Moreover, our data suggest that mechanisms beyond weight loss may be implicated in DM resolution following LSG and LRYGBP.