Obese Nondiabetic Subjects Research Articles

Beta Cell Function and Insulin Resistance in Nondiabetic, Prediabetic and Diabetic in a Subset of Obese Pakistani Population

Objective: To compare insulin resistance and beta-cell function in nondiabetic, prediabetic, and diabetic subjects in a subset of obese Pakistani population.
 Materials and Methods: Two hundred and ten obese subjects underwent anthropometric measurements. After overnight fasting for 8 hours, 6 cc blood was drawn for fasting blood glucose level, fasting insulin level. Blood glucose samples were taken after drinking 75 gm glucose in 260 ml water. HOMA IR and HOMA BETA% were calculated by the formula. Subjects were divided into obese nondiabetic, obese prediabetic and obese diabetic according to WHO criteria.
 Results: Out of 210 obese subjects, 53 (25.2%) were males and 157 (74.8%) were females. The mean BMI was 32.39±5.21. Mean abdominal circumference was 102.78±10.16. There were 101(48%) obese nondiabetic, 51(24%) were found to be obese prediabetic, 58(28%) were found to be obese diabetic. Mean insulin resistance in obese nondiabetic subjects was 2.8 ±3.7, in prediabetic 8.5± 12.3, in diabetic was 17.7±24.6. Mean HOMA beta was 245.3±267.4 in obese nondiabetic subjects, 290.5±298.4 in prediabetic, and 16.6±57 in diabetic.
 Conclusion: There was a significantly increased incidence of prediabetes and diabetes in obese subjects. Prediabetic and diabetic subjects were found to have marked insulin resistance. Beta-cell function was markedly reduced in diabetic subjects having a family history of diabetes, emphasizing the genetic predisposition to develop beta-cell exhaustion.

Low Levels of Serum Fetuin-A and Retinol-Binding Protein 4 Correlate with Lipoprotein Subfractions in Morbid Obese and Lean Non-Diabetic Subjects.

Background: Fetuin-A and retinol-binding protein 4 (RBP4) are secreted as both hepatokine and adipokine. These are involved in insulin resistance, obesity-related dyslipidemia, and atherosclerosis. To date, correlations of circulating fetuin-A and RBP4 with lipoprotein subfractions as well as high-density lipoprotein (HDL)-linked proteins have not been entirely investigated in morbid obese and lean non-diabetic subjects. Methods: One-hundred obese non-diabetic patients (body mass index, BMI: 42.5 ± 8.1 kg/m2) along with 32 gender and age-matched normal weight controls (BMI: 24.5 ± 2.5 kg/m2) were enrolled in our study. Serum fetuin-A and RBP4 were measured by ELISA. Lipoprotein subfractions were distributed by Lipoprint gelelectrophoresis. Results: Serum fetuin-A and RBP4 were unexpectedly lower in obese patients (p < 0.01 and p < 0.01, respectively) compared to controls and correlated with each other (r = 0.37; p < 0.001). Fetuin-A had positive correlations with HDL-C (r = 0.22; p = 0.02), apolipoprotein AI (apoAI) (r = 0.33; p < 0.001), very-low density lipoprotein (VLDL) subfraction (r = 0.18; p = 0.05), and large HDL subfraction levels (r = 0.3; p = 0.001) but did not show correlation with carbohydrate parameters in all subjects. RBP4 correlated positively with HDL-C (r = 0.2; p = 0.025), apoAI (r = 0.23; p = 0.01), VLDL subfraction (r = 0.37; p < 0.001), intermediate HDL subfraction (r = 0.23; p = 0.01), and small HDL subfraction (r = 0.21; p = 0.02) concentrations, as well as C-peptide levels in overall participants. Backward stepwise multiple regression analysis showed that serum fetuin-A concentration is best predicted by RBP4 and large HDL subfraction. In model 2, VLDL subfraction was the independent predictor of serum RBP4 level. Conclusions: Our data may indicate a potential role of fetuin-A and RBP4 in impaired lipoprotein metabolism associated with obesity.

Serum fetuin-A and retinol-binding protein 4 correlate with lipoprotein subfractions in obese and lean non-diabetic subjects

Background and Aims: Fetuin-A and retinol-binding protein 4 (RBP4) are secreted as both hepatokine and adipokine, and are involved in insulin resistance, obesity related dyslipidemia and atherosclerosis. To date, associations of circulating fetuin-A and RBP4 with lipoprotein subfractions and high-density lipoprotein (HDL)-linked proteins have not been completely investigated in morbid obese and lean non-diabetic subjects.

Postprandial glucose and HbA1c are associated with severity of obstructive sleep apnoea in non-diabetic obese subjects

IntroductionObstructive sleep apnoea (OSA) is an underdiagnosed condition frequently associated with glycaemic control impairment in patients with type 2 diabetes.AimTo assess the relationship between glycometabolic parameters and OSA in obese non-diabetic subjects.MethodsNinety consecutive subjects (mean age 44.9 ± 12 years, mean BMI 42.1 ± 9 kg/m2) underwent polysomnography and a 2-h oral glucose tolerance test (OGTT).ResultsOSA was identified in 75% of subjects, with a higher prevalence of males compared to the group of subjects without OSA (62% vs 32%, p = 0.02). Patients with OSA had comparable BMI (42.8 kg/m2 vs 39.4 kg/m2), a higher average HbA1c (5.8% vs 5.4%, p < 0.001), plasma glucose at 120 min during OGTT (2 h-PG; 123 mg/dl vs 97 mg/dl, p = 0.009) and diastolic blood pressure (81.1 mmHg vs 76.2 mmHg, p = 0.046) than obese subjects without OSA. HbA1c and 2 h-PG were found to be correlated with the apnoea-hypopnoea index (AHI; r = 0.35 and r = 0.42, respectively) and with percent of sleep time with oxyhaemoglobin saturation < 90% (ST90; r = 0.44 and r = 0.39, respectively). Further, in a linear regression model, ST90 and AHI were found to be the main determinants of 2 h-PG (β = 0.81, p < 0.01 and β = 0.75, p = 0.02, respectively) after controlling for age, sex, waist circumference, physical activity, and C-reactive protein. Similarly, ST90 and AHI persisted as independent determinants of HbA1c (β = 0.01, p = 0.01 and β = 0.01, p = 0.01, respectively).ConclusionBeyond the traditional clinical parameters, the presence of a normal-high value of 2 h-PG and HbA1c should raise suspicion of the presence of OSA in obese subjects.

Correlation between Serum Lipid Parameters and Interleukin-10 Concentration in Obese Individuals.

BackgroundThe role of interleukin-10 (IL-10) in humans is controversial because IL-10 has been proposed to exhibit both pro- and anti-inflammatory effects. We aimed to determine the relationships between the changes in these parameters in obese individuals participating in a weight-reduction program.MethodsWe measured cardiometabolic parameters including lipid profile and serum IL-10 concentration before and after completion of a 12-week weight-reduction program in 63 non-diabetic obese subjects with a body mass index ≥27 kg/m2 who had comorbid hypertension or dyslipidemia. All the participants were provided with individual intervention sessions designed to implement lifestyle modifications and administered 120 mg orlistat three times daily for 12 weeks. The relationships between changes in serum IL-10 concentration and changes in cardiometabolic risk factors were analyzed.ResultsChanges in serum IL-10 concentration were significantly negatively correlated with changes in total cholesterol (r=−0.377), high-density lipoprotein cholesterol (HDL-C; r=−0.377), and low-density lipoprotein cholesterol (LDL-C; r=−0.278) concentrations. However, there were no correlations between changes in serum IL-10 concentration and changes in other cardiometabolic parameters.ConclusionSerum IL-10 concentration can increase as serum total cholesterol decreases. Additional studies are needed to explore the mechanisms linking changes in serum IL-10 with serum LDL-C and HDL-C concentrations.

New emerging roles of the novel hepatokine SERPINB1 in type 2 diabetes mellitus: Crosstalk with β-cell dysfunction and dyslipidemia

Diabetes mellitus (DM) is a devastating metabolic disease. Recently, the cross-talk between insulin-secreting-β-cells and various organs has sparked much interest. SerpinB1 emerged as a novel hepatokine inducing β-cell proliferation. However, its role in type-2-DM (T2DM) patients has not been adequately studied. This study was designed to investigate its circulating levels in subjects with/without T2DM, and to study its association with β-cell function, as well as various glycemic-control and lipid-profile parameters. Anthropometric data and biochemical markers including fasting plasma glucose (FPG), HbA1C % and lipid profile parameters were measured in 55 T2DM patients, as well as 30 healthy nondiabetic subjects. Serum serpinB1, insulin and C-peptide levels were measured by ELISA. The homeostasis model assessment of both β-cell function (HOMA2-β%) and insulin resistance (HOMA-IR) were calculated. SerpinB1 levels were found to be significantly lower in T2DM patients 0.7 (0.2-12.4) ng/mL, compared to nondiabetic subjects 1.2 (0.94-24) ng/mL, P < 0.001, regardless of glycemic control, obesity, or insulin resistance. Additionally, serpinB1 levels were found to be positively associated with C-peptide, HOMA2-β% in all subjects; and BMI only in non-DM subjects; while negatively associated with FPG, HbA1C% and lipid-profile parameters. Higher serum serpinB1 levels were found to be associated with lower susceptibility for T2DM. Conclusively, serpinB1 is associated with various aspects of β-cell dysfunction, glycemic-control, and dyslipidemia with a possible role in β-cell compensation in obese nondiabetic subjects. The results of the current study shed lights on potential novel roles of serpinB1 in T2DM besides its action as an inducer for β-cell proliferation.

The relationship between specialized pro-resolving lipid mediators, morbid obesity and weight loss after bariatric surgery

Obesity and diabetes are associated with chronic inflammation. Specialized pro-resolving lipid mediators (SPMs)—resolvins (Rv), protectins (PD) and maresins (MaR)—actively resolve inflammation. Bariatric surgery achieves remission of diabetes, but mechanisms are unclear. We measured SPMs and proinflammatory eicosanoid levels using liquid chromatography-tandem mass spectrometry in 29 morbidly obese subjects (13 with diabetes) and 15 nondiabetic, mildly obese subjects. Compared to the mildly obese, the morbidly obese had higher levels of SPMs—RvD3, RvD4 and PD1—and white blood cells (WBC) and platelets. Post-surgery, SPM and platelet levels decreased in morbidly obese nondiabetic subjects but not in diabetic subjects, suggesting continued inflammation. Despite similar weight reductions 1 year after surgery (44.6% vs. 46.6%), 8 diabetes remitters had significant reductions in WBC and platelet counts whereas five non-remitters did not. Remitters had a 58.2% decrease (p = 0.03) in 14-HDHA, a maresin pathway marker; non-remitters had an 875.7% increase in 14-HDHA but a 36.9% decrease in MaR1 to a median of 0. In conclusion, higher levels of RvD3, PD1 and their pathway marker, 17-HDHA, are markers of leukocyte activation and inflammation in morbid obesity and diabetes and diminish with weight loss in nondiabetic but not diabetic subjects, possibly representing sustained inflammation in the latter. Lack of diabetes remission after surgically-induced weight loss may be associated with reduced ability to produce MaR1 and sustained inflammation.

The Usefulness of Diagnostic Panels Based on Circulating Adipocytokines/Regulatory Peptides, Renal Function Tests, Insulin Resistance Indicators and Lipid-Carbohydrate Metabolism Parameters in Diagnosis and Prognosis of Type 2 Diabetes Mellitus with Obesity.

The quantitative analysis of selected regulatory molecules, i.e., adropin, irisin, and vaspin in the plasma of obese patients with newly diagnosed, untreated type 2 diabetes mellitus, and in the same patients after six months of using metformin, in relation to adropinemia, irisinemia and vaspinemia in obese individuals, was performed. The relationship between plasma concentration of the adipocytokines/regulatory peptides and parameters of renal function (albumin/creatinine ratio—ACR, estimated glomerular filtration rate—eGFR), values of insulin resistance indicators (Homeostatic Model Assessment of Insulin Resistance (HOMA-IR2), Homeostatic Model Assessment of Insulin Sensitivity (HOMA-S), Homeostatic Model Assessment of β-cell function (HOMA-B), quantitative insulin sensitivity check index (QUICKI), insulin), and parameters of carbohydrate-lipid metabolism (fasting plasma glucose—FPG, glycated hemoglobin—HbA1C, estimated glucose disposal rate—eGDR, fasting lipid profile, TG/HDL ratio) in obese type 2 diabetic patients was also investigated. Circulating irisin and vaspin were found significantly different in subjects with metabolically healthy obesity and in type 2 diabetic patients. Significant increases in blood levels of both analyzed adipokines/regulatory peptides were observed in diabetic patients after six months of metformin treatment, as compared to pre-treatment levels. The change in plasma vaspin level in response to metformin therapy was parallel with the improving of insulin resistance/sensitivity parameters. An attempt was made to identify a set of biochemical tests that would vary greatly in obese non-diabetic subjects and obese patients with type 2 diabetes, as well as a set of parameters that are changing in patients with type 2 diabetes under the influence of six months metformin therapy, and thus differentiating patients′ metabolic state before and after treatment. For these data analyses, both statistical measures of strength of the relationships of individual parameters, as well as multidimensional methods, including discriminant analysis and multifactorial analysis derived from machine learning methods, were used. Adropin, irisin, and vaspin were found as promising regulatory molecules, which may turn out to be useful indicators in the early detection of T2DM and differentiating the obesity phenotype with normal metabolic profile from T2DM obese patients. Multifactorial discriminant analysis revealed that irisin and vaspin plasma levels contribute clinically relevant information concerning the effectiveness of metformin treatment in T2D patients. Among the sets of variables differentiating with the highest accuracy the metabolic state of patients before and after six-month metformin treatment, were: (1) vaspin, HbA1c, HDL, LDL, TG, insulin, and HOMA-B (ACC = 88 [%]); (2) vaspin, irisin, QUICKI, and eGDR (ACC = 86 [%]); as well as, (3) vaspin, irisin, LDL, HOMA-S, ACR, and eGFR (ACC = 86 [%]).

Evaluation of gingival and periodontal status in obese and non-obese type II diabetic patients - a cross sectional study.

ObjectiveThe aim of this study was to evaluate gingival and periodontal status in obese and non-obese type II Diabetic Patients.MethodsThe study population comprised of 75 subjects visiting the outpatient department of our institution, divided into three different groups, group 1 (obese diabetic), group 2 (non-obese diabetic), and group 3 (obese, non-diabetic). Diabetic status was assessed with HbA1c values and obesity status was assessed by body mass index (BMI) score greater than or equal to 30 kg/m2. Gingival and periodontal status were assessed using the Gingival Index (GI) and Community Periodontal Index (CPI) respectively.ResultsThe mean gingival index score in group 1, group 2, and group 3 were 1.58, 1.54, and 1.25, respectively. Gingival status was poor among obese and non-obese diabetic subjects (Groups 1 and 2) when compared with obese non-diabetic patients (Group 3). The periodontal status showed that periodontal pockets were increased in diabetic obese group (15.4%), followed by diabetic non obese (4.66%), and non-diabetic obese (2%) group respectively and loss of attachment was severe in diabetic obese group (60.7%), followed by diabetic non obese (45.9%) and non-diabetic obese (15.3%) respectively.ConclusionGingival and periodontal status was poor in the obese diabetic group compared to non-obese diabetic and obese non diabetic group. Hence, the risk of gingivitis and periodontitis in obese diabetic patients should be addressed earlier to prevent further complications and achieve a good oral health status.

Cholesterol 25-hydroxylase (CH25H) as a promoter of adipose tissue inflammation in obesity and diabetes

ObjectiveExpansion of visceral adipose tissue (VAT) and metabolic inflammation are consequences of obesity and associated with type 2 diabetes (T2DM). Metabolically activated adipose tissue macrophages (ATMs) undergo qualitative and quantitative changes that influence their inflammatory responses. How these cells contribute to insulin resistance (IR) in humans is not well understood. Cholesterol 25-Hydroxylase (CH25H) converts cholesterol into 25-Hydroxycholesterol (25-HC), an oxysterol that modulates immune responses. Using human and murine models, we investigated the role of CH25H in metabolic inflammation. MethodsWe performed transcriptomic (RNASeq) analysis on the human whole AT biopsies and sorted ATMs from obese non-diabetic (NDM) and obese diabetic (DM) subjects to inquire if CH25H was increased in DM. We challenged mice lacking Ch25h with a high-fat diet (HFD) to characterize their metabolic and immunologic profiling. Ch25h KO mice and human adipose tissue biopsies from NDM and DM subjects were analyzed. LC-MS was conducted to measure 25-HC level in AT. In vitro analysis permitted us to investigate the effect of 25-HC on cytokine expression. ResultsIn our RNASeq analysis of human visceral and subcutaneous biopsies, gene pathways related to inflammation were increased in obese DM vs. non-DM subjects that included CH25H. CH25H was enriched in the stromal vascular fraction of human adipose tissue and highly expressed in CD206+ human ATMs by flow cytometry analysis. We measured the levels of the oxysterols, 25-HC and 7α25diHC, in human visceral adipose tissue samples and showed a correlation between BMI and 25-HC. Using mouse models of diet-induced obesity (DIO), we found that HFD-induced Ch25h expression in eWAT and increased levels of 25-HC in AT. On HFD, Ch25h KO mice became obese but exhibited reduced plasma insulin levels, improved insulin action, and decreased ectopic lipid deposit. Improved insulin sensitivity in Ch25h KO mice was due to attenuation of CD11c+ adipose tissue macrophage infiltration in eWAT. Finally, by testing AT explants, bone marrow-derived macrophages (BMDMs) and SVF cells from Ch25h deficient mice, we observed that 25-HC is required for the expression of pro-inflammatory genes. 25-HC was also able to induce inflammatory genes in preadipocytes. ConclusionsOur data suggest a critical role for CH25H/25-HC in the progression of meta-inflammation and insulin resistance in obese humans and mouse models of obesity. In response to obesogenic stimuli, CH25H/25-HC could exert a pro-inflammatory role.

Influence of obese phenotype on metabolic profile, inflammatory mediators and stemness of hADSC in adipose tissue.

Unhealthy dietary practices, sedentary life style and lack of physical exercise in developing countries like India are major contributors of metabolic syndrome like obesity and diabetes. Obesity in Indians is defined at Body Mass Index (BMI, kg/m2) >25 and characterized as metabolically obese. A preliminary study performed to explore ramification of obesity on metabolic profile of adipose tissue and adipose derived stem cells (ADSC) from control and obese Indians. Adipose tissue/lipoaspirates from both control (BMI≤23) subjects, and non-diabetic obese Indians subjects (BMI≥25), were scrutinized for expressions of lipogenic genes, inflammatory mediators, stored adipokine levels, and insulin signaling proteins. Further, hADSC were isolated and immune-phenotyped from both the subject groups. Comparative assessments between chADSC and ohADSC were carried out for growth kinetics, expressions of pluripotent genes, adipogenic transcriptional factors, RUNX2, inflammatory mediators (IM), insulin signaling proteins, adipogenic and osteogenic differentiation. Adipose tissue of obese subjects depicted high leptin and resistin levels with reduced adiponectin levels. Expressions of IM and insulin signaling proteins were elevated compared to those of control subjects. hADSC of obese subjects demonstrated diminished proliferation, altered pluripotent genes, aggravated inflammation, adipogenesis with reduced osteogenesis. hADSC of obese had established insulin resistance compared to those of control subjects. This is the first study that describes hADSC of metabolically obese Indians have insulin resistance at lower BMI compared to Caucasians exemplifying plausible role in diminishing stemness of hADSC. Study alarms Indians to restore healthy dietary habits and assess quality of hADSC in regenerative therapy.

Exercise and apulian hypocaloric diet affect adipokine changes and gastric banding-induced weight loss: A prospective study on severe obese subjects.

BackgroundAdiponectin and Resistin correlate with insulin sensitivity and cardiovascular risk, respectively. This study aimed to identify lifestyle factors that modulate changes in Adiponectin and Resistin levels after gastric banding positioning (LapGB).Materials and methodsBefore (T0), 3 months (T3), 6 months (T6), and 12 months (T12) after LapGB, serum Adiponectin and Resistin levels were evaluated in a single-centre prospective study including a cohort of 27 non-diabetic obese subjects (S-Ob, BMI ≥35 kg/m2). After surgery, a dietitian checked the adherence of S-Ob to an Apulian hypocaloric diet (aphypoD)/physical activity (phA) and, according to their high or low compliance to aphypoD/phA, S-Ob were included in group 1 (n = 14) or 2 (n = 13) respectively. Serum Adiponectin and Resistin were also measured in 10 healthy controls.ResultsAt baseline, Resistin levels were significantly higher and Adiponectin levels significantly lower in S-Ob than in controls. After surgery, group 1 showed a 50.2% excess weight loss (%EWL), significantly decreased Resistin levels at T12 and increased Adiponectin levels at both T6 and T12 as compared with baseline. Group 2 showed 24.6 %EWL at T12, decreased Adiponectin levels at T6 and T12 as compared with baseline, but unaltered Resistin levels. After surgery, group 1 followed aphypoD/phA, while group 2 did not.ConclusionsLapGB fails to improve cardiovascular risk markers (Resistin) in S-Ob not improving lifestyle. Future studies might investigate these findings in a larger cohort and display whether aphypoD is more effective than other dietary intervention on cardiovascular risk in subjects undergoing LapGB or other Bariatric procedures.

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.

Association between type 2 diabetes mellitus and Helicobacter pylori infection among Saudi patients attending National Guard Primary Health Care Centers in the Western Region, 2018.

BACKGROUND:Reports on Helicobacter pylori infection in diabetics are inconsistent and contradictory. This study attempted to identify the possible association between type 2 diabetes and H. pylori infection.MATERIALS AND METHODS:Following a cross-sectional design, participants were recruited from four National Guard Primary Health Care Centers in Jeddah City, Saudi Arabia. The study was conducted from December 2017 to November 2018. All participants underwent hemoglobin A1C (HbA1c) assessment and stool antigen test for H. pylori.RESULTS:A total of 212 type 2 diabetic patients aged 40 years or more, and 209 age-matched nondiabetic subjects were included in the study. About one-quarter of the diabetics and nondiabetics were positive for H. pylori (26.9% and 26.3%, respectively). There was no significant difference. The prevalence of H. pylori did not differ significantly in the type 2 diabetics, with regard to their age groups, gender, smoking status, body mass index, chronic diseases, their HbA1c level, duration of diabetes, or received type of therapy. The prevalence of H. pylori was significantly higher in overweight and obese nondiabetic subjects (P = 0.013). Obese participants in both groups had the highest prevalence of infection (57.9% and 54.5%, respectively, P = 0.038).CONCLUSION:About one-quarter of type 2 diabetics and nondiabetics in Jeddah City have H. pylori infection. There is no association between diabetes and H. pylori infection. H. pylori was significantly higher in patients with a high body mass index.

Viscoelastic characterization of diabetic and non-diabetic human adipose tissue.

Obesity-induced chronic inflammation and fibrosis in adipose tissue contributes to the progression of type 2 diabetes mellitus (DM). While fibrosis is known to induce mechanical stiffening of numerous tissue types, it is unknown whether DM is associated with alterations in adipose tissue mechanical properties. The purpose of this study was to investigate whether DM is associated with differences in bulk viscoelastic properties of adipose tissue from diabetic (DM) and non-diabetic (NDM) obese subjects. Bulk shear rheology was performed on visceral (VAT) and subcutaneous (SAT) adipose tissue, collected from obese subjects undergoing elective bariatric surgery. Rheology was also performed on the remaining extracellular matrix (ECM) from decellularized VAT (VAT ECM). Linear mixed models were used to assess whether correlations existed between adipose tissue mechanical properties and DM status, sex, age, and body mass index (BMI). DM was not associated with significant differences in adipose tissue viscoelastic properties for any of the tissue types investigated. Tissue type dependent differences were however detected, with VAT having significantly lower shear storage and loss moduli than SAT and VAT ECM independent of DM status. Although DM is typically associated with adipose tissue fibrosis, it is not associated with differences in macroscopic adipose tissue mechanical properties.

Effect of Bariatric Surgery on High-Density Lipoprotein (HDL) Cholesterol in Non-diabetic Patients with Severe Obesity.

This study evaluated changes in serum high-density lipoprotein cholesterol (HDL-C) induced by laparoscopic bariatric surgery (BS) in non-diabetic obese subjects with low (L-HDL-C) or normal (N-HDL-C) levels of HDL-C. We assessed whether increased HDL-C is associated with weight loss, serum non-HDL cholesterol (non-HDL-C), serum triglycerides (TG), and physical activity (PA) before and 6 and 15months after BS. In this prospective cohort study, 71 subjects undergoing BS (42 by Roux-en-Y gastric bypass and 29 by sleeve gastrectomy) were evaluated for the % Excess Weight Loss (%EWL), waist circumference (WC), serum levels of glucose, glycosylated hemoglobin, TG, HDL-C, non-HDL-C, and LDL-C, and the degree, time, and energy expenditure related to PA. The short version of the International Physical Activity Questionnaire was used to assess PA. Levels of HDL-C significantly increased 15months after BS (p < 0.001) in subjects with low (p < 0.001) or normal (p = 0.017) values at baseline. A similar %EWL, decrease in WC, glucose, non-HDL-C, and LDL-C levels and increase in energy expenditure related to PA, was observed in both groups (L-HDL-C and N-HDL-C) at 15months after BS. However, the L-HDL-C group presented greater decrease in TG levels compared with N-HDL-C group (p = 0.004). In subjects with increased HDL-C 15months after BS, there was an association between this increase and the %EWL (p = 0.030), but there was no association with the change in PA. Irrespective of PA after BS, subjects with low and normal HDL-C levels at baseline showed an increase in HDL-C after BS, and this increase was associated with %EWL induced by BS.

Serum level of insulin-like growth factor-I in type 2 diabetic patients: impact of obesity.

Background Insulin-like growth factor-I (IGF-I) is homologous to proinsulin and possesses glucose reducing activity. The association between the level of IGF-I and diabetes has been highlighted. However, this association is controversial due to the influence of different factors including obesity. The aim of the study was to evaluate serum level of IGF-I in type 2 diabetic patients compared to control subjects. Materials and methods A cross-sectional study involving 100 participants was conducted. Serum levels of IGF-I were measured using enzyme-linked immunosorbent assay (ELISA) and the fasting plasma glucose (FPG) levels were measured using the glucose oxidase method. Results IGF-I levels in the diabetic patients were significantly lower than in non-diabetic control subjects (105.13 ± 6.34 vs. 159.96 ± 9.62 ng/mL, p < 0.0001). Among the diabetic group, there was no significant difference in IGF-I levels between obese diabetic patients and non-obese diabetic patients, p = 0.18. Similarly, among the non-diabetic group, a non-significant difference was found in IGF-I levels between obese non-diabetic and non-obese non-diabetic subjects, p = 0.156. However, among the obese group, obese diabetic patients had significantly lower IGF-I serum levels compared to obese non-diabetic subjects (112.07 ± 7.97 vs. 147.07 ± 13.05 ng/mL, p = 0.02). Furthermore, among the non-obese group, the non-obese diabetic patients had significantly lower IGF-I serum levels compared to the non-obese non-diabetic subjects (91.66 ± 9.93 vs. 171.86 ± 13.86 ng/mL, p < 0.0001). No significant associations were observed between IGF-I level and any of the age, gender, body mass index (BMI), FPG levels, or the duration of diabetes. Conclusions Type 2 diabetes mellitus is associated with lower levels of IGF-I regardless to the presence or absence of obesity.

Radiologic evidence that hypothalamic gliosis is improved after bariatric surgery in obese women with type 2 diabetes.

Hypothalamic neurons play a major role in the control of body mass. Obese subjects present radiologic signs of gliosis in the hypothalamus, which may reflect the damage or loss of neurons involved in whole-body energy homeostasis. It is currently unknown if hypothalamic gliosis (1) differs between obese nondiabetic (ND) and obese diabetic subjects (T2D) or (2) is modified by extensive body mass reduction via Roux-n-Y gastric bypass (RYGB). Fifty-five subjects (all female) including lean controls (CT; n = 13), ND (n = 28), and T2D (n = 14) completed at least one study visit. Subjects underwent anthropometrics and a multi-echo MRI sequence to measure mean bilateral T2 relaxation time in the mediobasal hypothalamus (MBH) and two reference regions (amygdala and putamen). The obese groups underwent RYGB and were re-evaluated 9 months later. Analyses were by linear mixed models. Analyses of T2 relaxation time at baseline showed a group by region interaction only in the MBH (P < 0.0001). T2D had longer T2 relaxation times compared to either CT or ND groups. To examine the effects of RYGB on hypothalamic gliosis a three-way (group by region by time) mixed effects model adjusted for age was executed. Group by region (P < 0.0001) and region by time (P = 0.0005) interactions were significant. There was a reduction in MBH relaxation time by RYGB, and, although the T2D group still had higher T2 relaxation time overall compared to the ND group, the T2D group had significantly lower T2 relaxation time after surgery and the ND group showed a trend. The degree of reduction in MBH T2 relaxation time by RYGB was unrelated to clinical outcomes. T2 relaxation times, a marker of hypothalamic gliosis, are higher in obese women with T2D and are reduced by RYGB-induced weight loss.

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.

2095-P: Association between Markers of Neuro and Systemic Inflammation and Cognitive Function in Obesity

Obesity is associated with alterations in brain structure and cognitive impairment. The mechanisms underlying obesity related decline in cognitive function are not well understood. Obesity related chronic systemic inflammation is postulated to be one of the potential mechanisms leading to cognitive dysfunction. It is unknown whether inflammation impacts brain areas important for higher level cognition such as the anterior cingulate cortex (ACC). Elevated myo-inositol (Ins), as measured by magnetic resonance spectroscopy (MRS), may be a marker of neuroinflammation and reflects activated astrocytes and microglia. We hypothesized that obese subjects (OB) will have higher ACC Ins compared to normal weight controls (CON) and that higher Ins will be associated with elevated blood inflammatory markers and reduced cognitive performance. We examined neurochemical profile from a 24x24x12mm3 voxel over the ACC using 1H MRS at 3 and 7 Tesla (T), in 5 nondiabetic OB (age 33 ± 5 years, BMI 43 ± 6 kg/m2) and 4 CON (age 36 ± 3 years, BMI 23 ± 3 kg/m2). Subjects also underwent cognitive testing and measurement of blood inflammatory markers. MR spectra were quantified using LCModel and the concentrations are expressed as a ratio to total creatine (tCr). There was a strong trend of higher Ins/tCr in ACC in OB compared to CON both at 3T (0.96 ± 0.06 vs. 0.88 ± 0.05, p =0.07) and 7T (0.91 ± 0.07 vs. 0.83 ± 0.08, p =0.17). Pearson correlations were used to test the relationship between Ins/tCr and markers of inflammation among all subjects. Higher blood inflammatory markers were associated with higher Ins/tCr (3T) in ACC (CRP, r=.74, p= 0.04; TNF α, r=.89, p=0.003) and with low levels of crystallized ability as measured by the NIH Toolbox Cognition Battery (CRP, r=-.73, p=0.03). Higher ACC Ins/tCr was also associated with poorer performance on a measure of fine motor coordination (r=.93, p=0.001). These data support the hypothesis that inflammation may contribute to the pathogenesis of brain and cognitive alterations in obesity. Disclosure A. Khan: None. J.M. Joers: None. M. Luciana: None. N. Rubin: None. Y. Siddiqui: None. S. Mangia: None. L.E. Eberly: None. S. Ikramuddin: Research Support; Self; Medtronic. E.R. Seaquist: Advisory Panel; Self; Eli Lilly and Company, Zucara Therapeutics Inc. Consultant; Self; 360 Consulting, MannKind Corporation. Research Support; Self; Eli Lilly and Company, JDRF, National Institutes of Health. Other Relationship; Self; American Diabetes Association, Sanofi, WebMD. G. Oz: None. A. Moheet: None. Funding National Institutes of Health