Non-obese Diabetics Research Articles

Associations between Serum Kallistatin Levels and Markers of Glucose Homeostasis, Inflammation, and Lipoprotein Metabolism in Patients with Type 2 Diabetes and Nondiabetic Obesity.

Kallistatin is an endogenous serine proteinase inhibitor with various functions, including antioxidative, anti-inflammatory, and anti-atherosclerotic properties. To date, associations between kallistatin and lipoprotein subfractions are poorly investigated. In this study, we enrolled 62 obese patients with type 2 diabetes (T2D), 106 nondiabetic obese (NDO) subjects matched in gender, age, and body mass index, as well as 49 gender- and age-matched healthy, normal-weight controls. Serum kallistatin levels were measured with ELISA, and lipoprotein subfractions were analyzed using Lipoprint® (Quantimetrix Corp., Redondo Beach, CA, USA) gel electrophoresis. Kallistatin concentrations were significantly higher in T2D patients compared to NDO and control groups. We found significant positive correlations between very-low-density lipoprotein (VLDL), small high-density lipoprotein (HDL) subfractions, glucose, hemoglobin A1c (HbA1c), betatrophin, and kallistatin, while negative correlations were detected between mean low-density lipoprotein (LDL) size, large and intermediate HDL subfractions, and kallistatin in the whole study population. The best predictor of kallistatin was HbA1c in T2D patients, high-sensitivity C-reactive protein (hsCRP) and betatrophin in NDO patients, and hsCRP in controls. Our results indicate that kallistatin expression might be induced by persistent hyperglycemia in T2D, while in nondiabetic subjects, its production might be associated with systemic inflammation. The correlation of kallistatin with lipid subfractions may suggest its putative role in atherogenesis.

Evaluation of the relationship of cytokines concentrations tumor necrosis factor-alpha, interleukin-6, and C-reactive protein in obese diabetics and obese non-diabetics: A comparative study.

Obesity has been linked to a low-grade inflammatory process in the white adipose tissue. Our study aims to detect the relationship between cytokine levels of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and C-reactive protein (CRP) in obese diabetics, compared to obese non-diabetics, Iraqi individuals. Ninety Iraqi adults, 45 type 2 diabetic and 45 non-diabetic obese, were selected as controls. Serum levels of TNF-α, IL-6, CRP, homeostatic model assessment for homeostasis model assessment of insulin resistance (HOMA-IR), body fat, and body mass index (BMI) were measured. The concentration of TNF-α, IL-6, and CRP were significantly greater in the obese diabetics, compared to the obese non-diabetics. BMI was significantly positively correlated with the concentration of TNF-α, IL-6, and CRP in the two groups. At the same time, HOMA-IR was non-significantly positively associated with them in obese diabetics. In contrast, the correlation was significantly positive between HOMA-IR with TNF-a, IL-6, and CRP in the obese non-diabetics group. Obese diabetics have more inflammation than obese non-diabetics as evidenced by the former's higher levels of TNF-α and IL-6. Obesity-related imbalances disrupt metabolic processes and increase CRP, TNF-, and IL-6 levels. Therefore, IR is promoted by the increase of cytokines.

Gender-Dependent Associations between Serum Betatrophin Levels and Lipoprotein Subfractions in Diabetic and Nondiabetic Obese Patients.

Betatrophin, also known as angiopoietin-like protein 8 (ANGPTL8), mainly plays a role in lipid metabolism. To date, associations between betatrophin and lipoprotein subfractions are poorly investigated. For this study, 50 obese patients with type 2 diabetes (T2D) and 70 nondiabetic obese (NDO) subjects matched in gender, age, and body mass index (BMI) as well as 49 gender- and age-matched healthy, normal-weight controls were enrolled. Serum betatrophin levels were measured with ELISA, and lipoprotein subfractions were analyzed using Lipoprint gel electrophoresis. Betatrophin concentrations were found to be significantly higher in the T2D and NDO groups compared to the controls in all subjects and in females, but not in males. We found significant positive correlations between triglyceride, very low density lipoprotein (VLDL), large LDL (low density lipoprotein), small LDL, high density lipoprotein (HDL) -6-10 subfractions, and betatrophin, while negative correlations were detected between betatrophin and IDL, mean LDL size, and HDL-1-5. Proportion of small HDL was the best predictor of betatrophin in all subjects. Small LDL and large HDL subfractions were found to be the best predictors in females, while in males, VLDL was found to be the best predictor of betatrophin. Our results underline the significance of serum betatrophin measurement in the cardiovascular risk assessment of obese patients with and without T2D, but gender differences might be taken into consideration.

Impaired Organokine Regulation in Non-Diabetic Obese Subjects: Halfway to the Cardiometabolic Danger Zone

Altered organokine expression contributes to increased cardiometabolic risk in obesity. Our aim was to evaluate the associations of serum afamin with glucose homeostasis, atherogenic dyslipidemia, and other adipokines in severe obesity to clarify the early metabolic alterations. 106 non-diabetic obese (NDO) subjects and 62 obese patients with type 2 diabetes matched for age, gender, and body mass index (BMI) were enrolled in this study. We compared their data with 49 healthy, lean controls. Serum afamin and retinol-binding protein 4 (RBP4), as well as plasma plasminogen activator inhibitor-1 (PAI-1), were measured with ELISA, and lipoprotein subfractions were analyzed using Lipoprint gel electrophoresis. Afamin and PAI-1 found to be significantly higher in the NDO and T2M group (p < 0.001 and p < 0.001, respectively) than in the controls. In contrast, RBP4 was unexpectedly lower in the NDO and T2DM group compared to controls (p < 0.001). Afamin showed negative correlations with mean LDL size and RBP4, but positive correlations with anthropometric, glucose/lipid parameters, and PAI-1 in both the overall patients and the in NDO + T2DM groups. BMI, glucose, intermediate HDL, and small HDL were predictors of afamin. Afamin may serve as a biomarker for the severity of cardiometabolic disturbances in obesity. The complexity of organokine patterns in NDO subjects draws attention to the diverse spectrum of obesity-related comorbidities.

The Correlation of Nrf2 rs6721961 Variants with the Risk of Type 2 Diabetes Mellitus and Obesity in Kurdistan of Iraq

Background: Type 2 diabetes mellitus (T2DM) is an endocrine and metabolic disease that the interaction of genetic background with environmental factors could enhance its risk. The nuclear erythroid-2-related factor 2 (Nrf2) protects cells against oxidative damage and toxicity. Objectives: This study aimed to determine the possible correlation between the Nrf2 gene variants with the risk of T2DM and obesity in the Kurdistan of Iraq. Methods: This study was conducted on 250 individuals categorized into 4 groups: 67 obese T2DM patients (body mass index (BMI) ≥ 30 kg/m2), 65 normal BMI diabetic patients (BMI &lt; 25 kg/m2), 62 obese non-diabetics, and 56 normal BMI non-diabetic individuals. The Nrf2 rs6721961 variants were identified by polymerase chain reaction (PCR) technique followed by digestion with the restriction enzyme of NgoMIV. Results: In the obese T2DM group, the levels of waist, and wrist circumference were significantly more than those of obese non-diabetic controls. Total antioxidant capacity level was not significantly different comparing patients with their controls. The Nrf2 T allele significantly decreased the risk of T2DM in normal BMI patients. In addition, carrying the T allele significantly reduced the risk of obesity. Conclusions: According to the results, significantly higher levels of anthropometric parameters was detected in obese T2DM compared with obese non-diabetic controls. The T allele of Nrf2 decreased T2DM risk among patients with normal BMI and obesity risk among Kurdish residents of Iraq. The findings of our research can be used in the prevention and management of T2DM by improving lifestyle habits.

Oxidative Stress, Antioxidant Enzymes and Risk of Hypertension in Obese Type 2 Diabetic Subjects in Osogbo, Osun State, Nigeria

Obesity is a chronic disease often associated with type 2 diabetes mellitus (T2DM) and metabolic syndrome. Coexistence of diabetes and hypertension have adverse clinical outcomes with micro and macrovascular complications. This study investigates the relationship of oxidative stress markers and antioxidants with occurrence of hypertension in obese type 2 diabetic subjects in Osun State, Nigeria. Four hundred and forty-five participants made up of 138 non-obese diabetics, 107 obese diabetic subjects attending two tertiary Hospitals in Osogbo in addition to 100 obese non-diabetes (positive controls) and 100 non-obese non-diabetes (negative controls) were enrolled in this study. FBS (9.55±0.13 mmol/l) and HbA1c (9.51±0.15 %) showed highest significant increase in obese diabetic subjects compared to other groups. Mean serum MDA was highest among obese diabetics (p&lt;0.05) while least values of superoxide dismutase (121.09±3.10 µ/ml) and catalase (24.97±0.66 pg/ml) were recorded in non-obese diabetics (p&lt;0.05). 21.0% of non-obese diabetics (n=29), 54.2% of obese diabetics (n=58), 45.0% of obese non-diabetic (n=45) and 21% of non-obese non-diabetics (n=21) were hypertensive. Age, sex, marital status, religion and occupation (χ2=9.856, 8.405, 22.701, 12.066 and 14.468) respectively were all significantly associated with occurrence of hypertension among obese diabetics. Receiver operating characteristics (ROC) and area under the curve (AUC) showed MDA having the highest cut off point among obese diabetes subject: 0.529 (0.42-0.64 95% CI) with a steep increase in LDL: 0.505(0.40-0.62 95% CI). This study revealed that increased oxidative stress and reduced antioxidant defense enzymes are strongly associated with dyslipidemia among obese diabetic subject.

Association of obesity in T2DM with differential polymorphism of ghrelin, growth hormone secretagogue receptor-1 and telomeres maintenance genes.

Although obesity and T2DM comorbidity is too frequent, the molecular basis of diabetic obesity is largely unexplained and barely investigated. Cross-sectional studies were conducted in Kingdom of Saudi Arabia (KSA) in 2013 and Kuwait in 2019. Fasting blood samples were obtained from a total of 216 T2DM patients (104 from KSA) and 193 nondiabetic subjects (93 from KSA) after their consents. Eight SNPs in 5 genes known to be associated with both obesity and T2DM, ghrelin (GHRL) and growth hormone secretagogue receptor -GHSR (KSA) and telomeres maintenance genes (Kuwait) were genotyped by rtPCR. Both patients and controls were grouped into obese and non-obese and sub-grouped into 4-BMI- grades: normal, overweight (OW), obese (OBS) and severely obese (SOBS). Showed that the only SNP which was distinguished between all groups/subgroups in all study subjects was the ACYP2 rs6713088G/C, where the common CC genotype was under-expressed in the obese compared to non-obese diabetics (17.8% vs. 40.4%, p 0.01) and between the 4-BMI-grade (p 0.025). Interestingly the same genotype was over-expressed in obese compared to non-obese non-diabetics (50% vs. 27.6%, p 0.04). Furthermore, the GHRL (rs27647C/T), GHSR (rs509030G/C) and TERC (rs12696304G/C) MAFs were significantly low in normal BMI patients; p=0.034, 0.008 and 0.011, respectively. This is the first report about the molecular distinction between the obese and non-obese diabetics, it showed the association of rs6713088G/C mutant allele with diabetic obesity, while the GHRL, GHSR and TERC SNPs were differentially expressed based on the BMI-grades.

-2548G>A LEP Polymorphism Is Positively Associated with Increased Leptin and Glucose Levels in Obese Saudi Patients Irrespective of Blood Pressure Status

Background and Objectives: In this study, we aimed to investigate the link between common -2548G>A (rs7799039) promoter variant of the human leptin gene (LEP) with leptin and serum glucose leptin levels in obese Saudi patients. Materials and Methods: A total of 206 Saudi adults (80 obese normotensive nondiabetics, 76 obese hypertensive with Type 2 Diabetes and 50 normotensive nondiabetic controls) were genotyped for -2548G>A LEP polymorphism using the polymerase chain reaction-restriction fragment-length polymorphism technique. Results: Participants with minor AA genotype had significantly higher blood glucose levels (6.8 ± 0.55 mmol/L vs. 5.8 ± 0.30 mmol/L; p < 0.04) and HOMA-IR (4.1 ± 0.84 vs. 2.6 ± 0.67; p = 0.03) against those carrying major GG genotype. Participants with heterozygous GA genotype had significantly higher serum leptin levels against those carrying major GG genotype (40.0 ± 2.6 ng/mL vs. 29.6 ± 2.6 ng/mL; p = 0.04). Further investigation showed that individuals with AA, GA, GA + AA genotypes are at greater risk of developing hyperglycemia compared to those with GG genotype [OR 3.7(1.6–8.4), p = 0.001; 3.2 (1.2–8.6), p = 0.03; 3.5 (1.6–7.7), p = 0.001, respectively]. Additionally, the -2548AA allele was shown to be a risk factor for hyperglycemia [OR 1.9 (1.2–3.0), p = 0.006]. Our data revealed no relationship between this variant of the LEP gene with systolic and diastolic BP, signifying that this genetic variant is not a significant marker of obesity and hypertension in the Saudi population. Conclusions: AA and GA genotypes and LEP gene -2548AA alleles may signify potent risk factors predisposing healthy individuals to develop T2DM regardless of blood-pressure profile.

Association of Hyperhomocysteinaemia with Hyperglycaemia, Dyslipidaemia, Hypertension and Obesity

There is conflicting scientific data about the link between, high homocysteine (Hcy) levels in the general population, and obesity. This is a case-control study aimed to assess the role of hyperhomocysteinemia in obesity and its associated illnesses, including hypertension, dyslipidemia, and hyperglycemia in Gezira state, Sudan. Two hundred and eleven participants were included in the study, 140 were obese (117 females and 23 males) and 71 were normal weight control, the obese median age was 49.49 ± 12.2 years. The control group consisted of 71 individuals with an average age of 45.78 ± 17.67 years. Among those who were already known to be obese, 67 (47.9%) reported having type II diabetes mellitus, 71 (50.7%) reported having hypertension, and 35 (25%) were obese without having either diabetes or hypertension. Three mls of venous blood from each participant were collected in the morning after a 12 h overnight fasting in Lithium heparin containers then the plasma was separated and stored at -80°C for analysis. Serum Hcy and lipid profile were measured using the enzymatic method by Cobas C 411 analyzer. In comparison to obese non-hypertensive, the results showed that obese hypertensive with Hcy levels > 15 mol/L had a considerably increased risk (OR 1.12). When Hcy levels > 15 mol/L were compared to obese diabetics and obese non-diabetics, insignificant difference was shown (P: 0.345). Males had a higher likelihood of having hyperhomocysteinemia than females did (OR 1.2). Homocysteine, cholesterol triglyceride, LDL, and HDL mean values were compared between case and control groups using the independent sample t-test, and the results revealed statistically significant (P: <0.05). Relationships between hyperhomocysteinaemia and cholesterol, triglycerides, LDL, and HDL in the group of obese individuals were not statistically significant (P: 0.574, 0.265, 0.748, and 0.14), respectively. Obesity and Hcyconcentrations were shown to be substantially correlated. However, there was no statistically significant association between baseline plasma Hcy levels and hyperglycemia, hypertension, or dyslipidemia.

Synergic effects of ultrasound and laser therapies on mesentery for management of obesity and diabetes in rats.

Nowadays, the mesentery as a new organ was discovered. Mesenteric events may play an important role in the pathophysiology of several diseases. The aim of our study was investigate the synergic effects of ultrasound (US) and laser therapies on mesentery in obese-hyperglycemic rats. The 25 male Wistar rats were randomized into five groups. Obese nondiabetic (OND) group: obese rats without diabetes and no treatment conditions; SHAM group: obese-hyperglycemic rats treated with placebo; US group: obese-hyperglycemic rats treated with US; LASER group: obese-hyperglycemic rats treated with laser and; US+LASER group: obese-hyperglycemic rats treated with US plus laser. An animal model of type 2 diabetes based on a hyperlipidemic diet combined with a low dose of streptozotocin was used in this study. Body mass and biochemical measurements were performed. GOT and GPT level showed a significant reduction in the treated groups than SHAM. The total cholesterol, triglycerides and very low-density lipoprotein (VLDL) levels showed significantly lower values for the US+LASER group. There was also reduced risk of cardiovascular diseases evidenced by Castelli index in the treated groups than SHAM. This study showed that the US and laser treatment on mesentery resulted to an improvement in biochemical measurements of the obese-hyperglycemic rats, especially the total cholesterol, triglycerides and VLDL levels.

Adipocytokines in Diabetes Mellitus: A Study from a Rural Setting in Haryana, India

Introduction: Diabetes Mellitus (DM) and Obesity are the biggest public health challenges of 21st century. Both these disorders are associated with several co-morbidities like hypertension, hyperlipidemia, Cardiovascular Diseases (CVD) etc., that may be linked to the underlying insulin resistance, hyperglycaemia, dyslipidemia, hyperinsulinemia and altered levels of adipocyte- derived hormones. Furthermore, clinical studies in humans have suggested the possible correlation of plasma concentration of several adipocytokines and measures of adiposity, insulin resistance and endothelial function in humans. Aim: To estimate and compare the serum levels of leptin and adiponectin in patients with Type 2 Diabetes Mellitus (T2DM) and in non-diabetic subjects with and without obesity. Materials and Methods: In the study, 200 T2DM patients (with and without obesity) and 200 non-diabetic subjects (with and without obesity) aged between 30-70 years of either sex were included. In all the subjects included in the study, serum leptin and adiponectin levels were estimated using Enzyme Linked Immunosorbent Assay (ELISA) method. Results: It was observed that the serum adiponectin levels decreased while leptin levels increased significantly (p&lt;0.001) in obese than non-obese diabetics. Similarly, obese non-diabetics showed higher serum leptin and lower adiponectin levels than their non-obese counterparts (p&lt;0.001). Conclusion: Serum levels of leptin and adiponectin are altered in subjects with T2DM and obesity which may indicate the potential role of adipocytokines as an important link between increased fat mass, insulin resistance, deranged glucose metabolism and endothelial dysfunction especially in diabetic patients.

Early disruption of nerve mitochondrial and myelin lipid homeostasis in obesity-induced diabetes.

Diabetic neuropathy is a major complication of diabetes. Current treatment options alleviate pain but do not stop the progression of the disease. At present, there are no approved disease-modifying therapies. Thus, developing more effective therapies remains a major unmet medical need. Seeking to better understand the molecular mechanisms driving peripheral neuropathy, as well as other neurological complications associated with diabetes, we performed spatiotemporal lipidomics, biochemical, ultrastructural, and physiological studies on PNS and CNS tissue from multiple diabetic preclinical models. We unraveled potentially novel molecular fingerprints underlying nerve damage in obesity-induced diabetes, including an early loss of nerve mitochondrial (cardiolipin) and myelin signature (galactosylceramide, sulfatide, and plasmalogen phosphatidylethanolamine) lipids that preceded mitochondrial, myelin, and axonal structural/functional defects; started in the PNS; and progressed to the CNS at advanced diabetic stages. Mechanistically, we provided substantial evidence indicating that these nerve mitochondrial/myelin lipid abnormalities are (surprisingly) not driven by hyperglycemia, dysinsulinemia, or insulin resistance, but rather associate with obesity/hyperlipidemia. Importantly, our findings have major clinical implications as they open the door to novel lipid-based biomarkers to diagnose and distinguish different subtypes of diabetic neuropathy (obese vs. nonobese diabetics), as well as to lipid-lowering therapeutic strategies for treatment of obesity/diabetes-associated neurological complications and for glycemic control.

Hypogonadism among obese type 2 diabetic men in South-Western Nigeria

Background: Studies have shown that hypogonadism is closely related to the development of Type 2 Diabetes. This study aimed to assess hypogonadism among type 2 diabetic and obese male patients in Southwest Nigeria.Methods: One hundred and twenty men consisting of thirty obese diabetics, thirty non-obese diabetics, thirty obese non-diabetics and thirty non-obese non-diabetics, were included in the study. Participants were interviewed to obtain data on biodata, reproductive characteristics, and anthropometry. Venous Blood was collected for the determination of fasting plasma Glucose, glycated haemoglobin, and reproductive hormonal levels.Results: The prevalence of hypogonadism in this study was 20.8%. The mean age of all the participants was 43.39 ± 5.21, most men being in the 40-44 years age group. In this age group, over a third (40%) of the men had low testosterone. Out of the 60 participants who were diabetic, 18 (30%) had low testosterone, two-third of whom (66.7%) were obese. Mean testosterone was significantly lower in obese diabetics when compared with non-obese diabetics. The mean testosterone and FSH were significantly lower in obese non-diabetics as well. Both diabetic and non-diabetic groups had significantly higher estrogen in the obese participants, than in the non-obese.Conclusion: In conclusion, hypogonadism is a common finding among diabetic men, and it occurs in higher frequency with coexisting obesity. Hence, a holistic approach in the treatment of male patients with hypogonadism, type 2 diabetics and obesity should be considered, in order to safeguard their reproductive health.&#x0D; Key Words: Hypogonadism, obesity, FSH, LH, testosterone, Nigeria.

Genetic determinants of obesity heterogeneity in type II diabetes

BackgroundAlthough obesity is considered as the main cause of Type II diabetes (T2DM), non-obese individuals may still develop T2DM and obese individuals may not.MethodThe mRNA expression of PI3K/AKT axis from 100 non-obese and obese participants with insulin sensitivity and insulin resistance states were compared in this study toward the understanding of obesity heterogeneity molecular mechanism.ResultIn present study, there was no statistically significant difference in gene expression levels of IRS1 and PTEN between groups, whereas PI3K, AKT2 and GLUT4 genes were expressed at a lower level in obese diabetic group compared to other groups and were statistically significant. PDK1 gene was expressed at a higher level in non-obese diabetic group compared to obese diabetic and non-obese non-diabetics groups. No statistically significant difference was identified in gene expression pattern of PI3K/AKT pathway between obese non-diabetics and non-obese non-diabetics.ConclusionThe components of PI3K/AKT pathway which is related to the fasting state, showed reduced expression in obese diabetic group due to the chronic over-nutrition which may induced insensitivity and reduced gene expression. The pathogenesis of insulin resistance in the absence of obesity in non-obese diabetic group could be due to disturbance in another pathway related to the non-fasting state like gluconeogenesis. Therefore, the molecular mechanism of insulin signalling in non-obese diabetic individuals is different from obese diabetics which more investigations are required to study insulin signalling pathways in greater depth, in order to assess nutritional factors, contribute to insulin resistance in obese diabetic and non-obese diabetic individuals.

Risk of fragility fractures in obesity and diabetes: a retrospective analysis on a nation-wide cohort.

The role of obesity and diabetes on fracture risk is yet poorly understood. Body mass index (BMI) and bone mineral density (BMD) are strongly correlated; however, patients with elevated BMI are not protected against fractures, configuring the obesity paradox. A similar controversial association has been also found in diabetic patients. Herein, we present a retrospective analysis on 59,950 women. Using a new web-based fracture risk-assessment tool, we have collected demographic (including BMI), densitometric, and clinical data (including history of vertebral or hip and non-vertebral, non-hip fractures, presence of comorbidities). We performed a propensity score generation with 1:1 matching for patients in the obese (BMI ≥ 30) and non-obese (BMI < 30) groups, in the diabetics and non-diabetics. Propensity score estimates were estimated using a logistic regression model derived from the clinical variables: age, lumbar spine T-score, and femoral neck T-score. We found an association between diabetes and fractures of any kind (OR 1.3, 95% CI 1.1-1.4 and 1.3, 95% CI 1.2-1.5 for vertebral or hip fractures and non-vertebral, non-hip fractures, respectively). Obesity, on the other hand, was significantly associated only with non-vertebral, non-hip fractures (OR 1.3, 95% CI 1.1-1.6). To estimate the individual effect of obesity and diabetes on bone health, we ran sensitivity analyses which included obese non-diabetic patients and non-obese diabetic patients, respectively. Non-obese diabetics had the highest risk of vertebral or hip fracture, whereas obese non-diabetics predominantly had non-vertebral, non-hip fracture's risk. These results should raise awareness in clinical practice when evaluating diabetic and/or obese patients.

Studies on Status of Oxidative Stress related Molecules and Enzymes in Obese with and without Diabetes in the Northern region of India

This study was done to assess the interrelationship of “oxidative stress-related molecules & enzymes” with obesity and diabetes. Xanthine oxidase (XO), malondialdehyde (MDA) representing lipid peroxidation and protein oxidative stress parameters such as advanced oxidation of protein products (AOPP), protein carbonyls (PC) and antioxidant enzyme activities in obese with or without type 2 diabetes mellitus (T2DM) were studied. This study enrolled 41 healthy controls, 41 obese non-diabetics, and 41obese T2DM patients. Biochemical parameters related to diabetes, oxidative stress and antioxidant enzymes were measured in all groups. The levels of XO, MDA, AOPP, and PC were significantly increased in obese with and without T2DM as compared to healthy controls (P < 0.001). However levels of antioxidants such as reduced glutathione (GSH) and activity of superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase (GST), glutathione peroxidase (GPx) were significantly decreased in obese with and without T2DM as compared to healthy control (P < 0.001 or P < 0.05). Positive correlations were found among XO with MDA (P = 0.006), PC (P = 0.012) in obese non-diabetic subjects and with MDA (P < 0.001), AOPP (P = 0.026), and PC (P = 0.003) in obese T2DM patients. Positive correlation were seen in MDA with AOPP (P = 0.017), PC (P = 0.046) in obese non-diabetic subjects and MDA with AOPP (P < 0.001), PC (P < 0.001) in obese T2DM patients. Also observed a significant correlation between AOPP and PC (P < 0.001) in both groups of obese. The present study results suggest that increased activity of xanthine oxidase, higher lipid peroxide generation, and higher levels of protein oxidative stress parameters (AOPP and PC) may be a most considerable mechanism in reducing the activity of antioxidant enzymes in obese with and without diabetic groups as compared to control group. However, extent of derangements is lower in obese subjects as compared to diabetic patients, thereby suggesting that obese subjects have a higher risk of diabetes as well as early onset of diabetes.

Effect of bariatric surgery on glycemic profiles in multiethnic obese nondiabetic Asians.

The effect of bariatric surgery on improvement and remission of type 2 diabetes (T2D) is well studied. The effect of surgery on glycemic profiles of obese, but nondiabetic individuals is unknown. We aimed to study changes in glycemic indices in obese nondiabetics undergoing bariatric surgery and correlate fat mass loss with changes in glycemic profiles. University Hospital, Singapore. A prospective database of nonT2D patients who underwent bariatric surgery between April 2009 and December 2014 was analyzed. Changes in weight, fat mass, and glycemic profiles, including glycated hemoglobin, C-peptide levels, and the homeostasis model assessment of insulin resistance were studied at 1- and 3-year follow-up. One hundred thirty-three nondiabetics underwent bariatric surgery in the study period. Twenty-nine (21.8%) patients were found to have impaired fasting glycemia. We observed reductions in mean fat mass from 47.4 ± 12.2 kg preoperatively to 27.8 ± 11.6 kg at 1 year. Despite mean fat mass regain to 33.9 ± 19.6 kg at 3 years, homeostasis model assessment of insulin resistance improved from severe insulin resistant state of >5.00 (7.13 ± 11.5) preoperatively to normal ranges of <3.00 (1.55 ± .91) at 3 years. Bariatric surgery results in significant sustained weight loss in obese nondiabetics and normalizes glycated hemoglobin and homeostasis model assessment of insulin resistance after surgery. It is a promising modality to prevent or delay the onset of T2D in obese nondiabetic patients. Further studies should be conducted in nondiabetics to assess the efficacy of bariatric surgery inprevention of T2D onset in the longer term.

Effects of Obesity and Diabetes on Oxidized Low Density Lipoproteins and CD36 Membrane Receptor (FS18-06-19)

ObjectivesClustering differentiating 36 (CD36), a scavenger receptor highly expressed in macrophages and monocytes, is implicated in the early stages of atherosclerosis due to its ability to internalize oxidized low density lipoprotein (oxLDL). Although obesity is a major risk for diabetes, some obese subjects seem to be more resistant to the development of metabolic and pathological disturbances. This study was designed to compare the concentration of circulating oxLDL and the expression of monocyte CD36 in obese diabetic (OD) and obese non-diabetic (OND) subjects, and tested whether bariatric surgery exerts similar effects in both groups MethodsBlood was collected prospectively from OD and OND subjects (n = 21 per group) before Roux-en-Y-gastric bypass (RYGB) and 12 months postoperatively. Plasma glucose and lipoproteins were measured enzymatically. Iinsulin and glycosylated hemoglobin A1c (GHbA1c) were analyzed by enzyme-linked immunosorbent (Elisa). Insulin resistance index (HOMA-IR) was calculated. The expression of monocytes CD36 was assayed by western blot and RT-PCR. ResultsAlthough OD and OND subjects had comparable body mass index Pre-RYGB (43 ± 9 vs 41 ± 8 kg/m2, respectively), blood insulin, HbA1c and HOMA-IR were significantly higher in OD (29 ± 5 μU/mL, 7.8 ± 0.8% and 9.8 ± 2.5, respectively) than OND subjects (19 ± 4 μU/mL, 5.7 ± 0.5% and 5.9 ± 1.4, respectively). In addition, the level of plasma oxLDL (49.2 ± 11.9 vs 31.4 + 9.5 mU/ml) was greater in OD than OND subjects. Moreover, the expression of monocyte CD36 (protein level and mRNA abundance) was significantly higher in OD than OND subjects. The effect of RYGB was beneficial in both OD and OND subjects. At 12 months post-RYGB, there were comparable reduction of BMI in OD and OND subjects. Plasma levels of insulin, HbA1c and HOMA-IR also declined in both groups, but the effect was stronger in OD subjects, leading to comparable final values between groups. Plasma oxLDL and monocyte CD36 expression were also reduced in both groups and were comparable at 12 months post-RYGB. ConclusionsThese results show that obese diabetic subjects exhibit high levels of oxLDL and monocyte CD36, both of which could increase the risk of cardiovascular diseases. RYGB-induced weight loss could be beneficial for both obese and obese diabetic subjects. Funding SourcesHackensack University Medical Center.

268-LB: Investigating the Role of MPO and ANGPTL6 in Obesity and Diabetes and Their Potential Role in Wound Healing

Purpose: Myeloperoxidase (MPO) is a major neutrophil-derived protein known to play an important role in inflammation, oxidative stress, and atherosclerosis. Like other angiopoietin-like protein (ANGPTL), ANGPTL6 is reported to regulate metabolic processes but is thought to counteract obesity through increased energy expenditure. This study evaluated the plasma level of both MPO and ANGPTL6 in obese and diabetic people to investigate their clinical association. Methods: A total of 204 people were enrolled in this study (109 nondiabetic and 95 T2D). ANGPTL6, MPO, and other biomarkers plasma levels were measured by ELISA. Results: MPO plasma level was unchanged between diabetics and nondiabetics, whereas ANGPTL 6 plasma level increased in diabetics (33.73±1.31 pg/mL) compared to nondiabetics (28.74±1.01 pg/mL) (P &amp;lt;0.003). However, MPO plasma level increased in obese diabetics (75.28±3.19 ng/mL) compared to non-obese diabetics (65.71±2.54 ng/mL) (P &amp;lt;0.02). Similarly, ANGPTL6 plasma level was increased in obese diabetics (35.74±1.68 pg/mL) compared to non-obese diabetics (29.05 ± 1.61 pg/mL) (P &amp;lt;0.01). Obese nondiabetics had a higher level of MPO compared to non-obese nondiabetics although it did not reach statistical significance (P = 0.05). In contrast, no changes in the plasma levels of ANGPTL6 were seen in nondiabetics irrespective of weight. Both MPO and ANGPTL plasma levels were higher in obese than non-obese people (P &amp;lt; 0.05). MPO was positively associated with ANGPTL6, TG, BMI, TNF alpha, HsCRP, IL6, and PAI1. Conclusion: Both MPO and ANGPTL6 seem to regulate obesity, although MPO might do it independently of diabetes status and they might be also involved in wound healing as previously reported. The positive association of MPO with several biomarkers of inflammation and atherosclerosis may underlie its pathogenic mechanism in obesity and diabetes related wound healing and other diabetes related pathways. Disclosure M.G. Qaddoumi: None. M. Abu-farha: None. P.T. Cherian: None. I. Al khairi: None. A.M. Channanath: None. M. Alanbaei: None. J. Abubaker: None. F. Al-Mulla: None.

STUDY OF RELATIONSHIP BETWEEN THE PROTEIN OXIDATION MARKERS AND ADIPOKINES IN OBESE TYPE 2 DIABETIC PATIENTS

Objective: This study was done to explore the correlation if any, between obesity markers adiponectin, leptin, and protein oxidative stress (OS) status in obese with and without type 2 diabetic mellitus (T2DM) patients.&#x0D; Methods: In the present study, 30 healthy subjects, 30 obese non-diabetics, and 30 obese T2DM patients were enrolled. Protein OS parameters such as advanced oxidation of protein products (AOPPs) and protein carbonyl (PC) were estimated. Serum leptin, adiponectin, and insulin levels were measured by ELISA.&#x0D; Results: The AOPP, PC, leptin, leptin adiponectin ratio (LAR), insulin, and homeostasis model assessment of insulin resistance (HOMA-IR) levels were significantly higher in obese non-diabetic and obese T2DM as compared to healthy control (p&lt;0.001). However, serum adiponectin levels were significantly lower in obese non-diabetic and obese T2DM as compared to control (p&lt;0.001). HOMA-IR and LAR both the index of IR were increased in obese non-diabetic and obese T2DM. Positive correlations were observed for AOPP with body mass index, PC in obese non-diabetic and with fasting blood glucose, postprandial blood glucose, HOMA-IR, and PC in obese T2DM. A negative correlation was found between PC and adiponectin in obese non-diabetic and obese T2DM. A significant inverse correlation was obtained between leptin and adiponectin in obese T2DM only.&#x0D; Conclusion: The present study suggested that increased protein OS, hyperinsulinemia, and hyperleptinemia may lead to hypoadiponectinemia in obese with and without T2DM. Moreover, determination of protein oxidation markers can be useful for monitoring the dysregulation of adipokines and glucose metabolism in obesity and T2DM.