Obese Diabetic Subjects Research Articles

Palmitate-induced IL6 expression ameliorated by chicoric acid through AMPK and SIRT1-mediated pathway in the PBMCs of newly diagnosed type 2 diabetes patients and healthy subjects

Inhibition of inflammation is one of the possible therapeutic approaches for Insulin resistance (IR) during type 2 diabetes mellitus (T2DM). In the current study we investigated the effects of palmitate and chicoric acid (CA) on inflammation in peripheral blood mononuclear cells (PBMCs) of newly diagnosed T2DM patients and healthy subjects and explored the mechanism by which palmitate and CA influence inflammation.20 newly diagnosed T2DM patients and 20 healthy subjects were recruited in our study. Blood sample were collected and PBMCs were isolated. Interleukin 6 (IL6), silent information regulator type 1 (SIRT1), AMP-activated protein kinase (AMPK) and phospho-AMPK (pAMPK) were evaluated both in vivo and in vitro. PBMCs were treated with palmitate and CA to investigate their effects on inflammation. IL6 and SIRT1 genes expression were evaluated by real-time PCR. The levels of IL6 in culture medium were measured by ELISA. Proteins levels of AMPK and pAMPK in PBMCs were detected by western blotting.IL6 expression was higher and SIRT1 expression and pAMPK levels were lower in PBMCs of diabetic patients and obese subjects compared to healthy subjects and non-obese subjects, respectively. CA significantly prevented against increased IL6 levels as well as its gene expression in PBMCs induced by palmitate. Also, CA returned reduction in SIRT1 expression and pAMPK levels mediated via palmitate to near control level.These findings reveal that CA reduces inflammation in PBMCs probably through upregulation of SIRT1 and pAMPK. Therefore, CA would be suggested as a novel agent for the treatment of T2DM.

Response to: Comment #2 on "Differences in Ventilatory Threshold for Exercise Prescription in Outpatient Diabetic and Sarcopenic Obese Subjects".

Response to: Comment #2 on "Differences in Ventilatory Threshold for Exercise Prescription in Outpatient Diabetic and Sarcopenic Obese Subjects".

Fetuin-A levels are increased in the adipose tissue of diabetic obese humans but not in circulation

BackgroundThe hepatokine fetuin-A is linked to obesity and type 2 diabetes, but its presence and expression in adipose tissue remain unclear. In this study, we aimed to assess the circulating levels of fetuin-A and its expression in subcutaneous adipose tissue (SAT) from diabetic and non-diabetic obese subjects and their modulation by exercise.MethodsSAT and blood were obtained from adults obese (diabetic, n=118 and non-diabetic, n=166) before and after a 3-month exercise program (diabetic, n=40 and non-diabetic, n=36, respectively). Plasma fetuin-A was assayed using ELISA. The presence and expression of fetuin-A in SAT, peripheral blood mononuclear cells (PBMCs) and cell lines (3T3-L1, THP-1, HepG2, RAW 264.7) were analysed using confocal microscopy, immunoblotting and qRT-PCR.ResultsPlasma fetuin-A level did not significantly differ between diabetic and non-diabetic obese subjects. However, when the non-diabetic group was divided into metabolically healthy and unhealthy phenotypes, significantly higher fetuin-A level was observed in the unhealthy sub-group. Circulating fetuin-A was mainly associated with glycaemic markers. In SAT, fetuin-A protein level was significantly higher in the diabetic obese subjects but its mRNA was not detected. Similarly, fetuin-A protein was detected in PBMCs, but its mRNA was not. In line with this, the use of various cell lines and culture media indicated that the presence of fetuin-A in SAT and PBMCs was due to its uptake from circulation rather than its endogenous expression. Finally, physical exercise decreased fetuin-A levels in both plasma and SAT in both groups.ConclusionsFetuin-A levels increased in association with diabetes in SAT but not in circulation in the obese subjects. Moreover, physical exercise decreased fetuin-A level. Fetuin-A potentially acts as a hepatokine taken up by other tissues, such as adipose tissue.

Comment #2 on "Differences in Ventilatory Threshold for Exercise Prescription in Outpatient Diabetic and Sarcopenic Obese Subjects".

Comment #2 on "Differences in Ventilatory Threshold for Exercise Prescription in Outpatient Diabetic and Sarcopenic Obese Subjects".

The Relationships between Serum Levels of Adipokines, Body Fat Distribution, and Subcutaneous Microvasculature in Type 2 Diabetic Subjects

The aim of the study: to determine the relationships between serum levels of adipokines, body fat distribution, density and ultrastructure of blood and lymphatic microvessels in subcutaneous adipose tissue (AT) in type 2 diabetic subjects. We observed 125 patients with type 2 diabetes, including 82 subjects with obesity, and 30 lean nondiabetic individuals matched by sex and age. The concentrations of leptin, resistin, visfatin, adipsin, and adiponectin in the fasting serum were determined by Multiplex analysis. The fat mass and AT distribution was assessed by DEXA. The samples of subcutaneous abdominal AT were obtained with the knife biopsy in 25 patients and in 15 healthy subjects. Immunohistochemistry for biomarkers CD-34, podoplanin (D2-40) and LYVE-1 was applied to identify the blood and lymphatic microvessels. The volume density, numeral density and ultrastructure of blood and lymphatic microvessels were assessed. Patients with diabetes, as compared to control, had significantly higher levels of leptin (p=0.004), resistin (p<0.0001), adipsin (p<0.0001) and visfatin (p=0.0003). The concentrations of leptin and adipsin were associated with total, truncal, android and gynoid fat mass. The levels of resistin and adiponectin demonstrated relationships with gynoid fat mass only. In obese diabetic subjects an increase in the volume and numeral density of podoplanin-expressing lymphatic vessels was observed. The swelling of cytoplasm, mitochondria, rough endoplasmic reticulum and reduced content of micropinocytic vesicles was revealed in lymphatic capillaries. The levels of leptin and adipsin, but not resistin and visfatin levels, correlated negatively with the numeral density of microvessels in subcutaneous AT (r=-0.53 and r=-0.32 respectively). In conclusion, the levels of circulating adipokines in patients with type 2 diabetes are related in varying degrees with body fat distribution and AT microvessel density. Disclosure V. Klimontov: None. D. Bulumbaeva: None. N.P. Bgatova: None. I. Taskaeva: None. O. Fazullina: None. N. Orlov: None. A.I. Korbut: None. S. Savchenko: None. V. Konenkov: None.

A Glucagon-Like Peptide-1 Receptor Agonist Lowers Weight by Modulating the Structure of Gut Microbiota.

In addition to improving glucose metabolism, liraglutide, a glucagon-like peptide-1 receptor agonist, has weight-loss effects. The underlying mechanisms are not completely understood. This study was performed to explore whether liraglutide could lower weight by modulating the composition of the gut microbiota in simple obese and diabetic obese rats. In our study, Wistar and Goto-Kakizaki (GK) rats were randomly treated with liraglutide or normal saline for 12 weeks. The biochemical parameters and metabolic hormones were measured. Hepatic glucose production and lipid metabolism were also assessed with isotope tracers. Changes in gut microbiota were analyzed by 16S rRNA gene sequencing. Both glucose and lipid metabolism were significantly improved by liraglutide. Liraglutide lowered body weight independent of glycemia status. The abundance and diversity of gut microbiota were considerably decreased by liraglutide. Liraglutide also decreased obesity-related microbial phenotypes and increased lean-related phenotypes. In conclusion, liraglutide can prevent weight gain by modulating the gut microbiota composition in both simple obese and diabetic obese subjects.

Circulating LECT2 levels in newly diagnosed type 2 diabetes mellitus and their association with metabolic parameters: An observational study.

Leukocyte cell-derived chemotaxin 2 (LECT2) is a hepatokine expressed in hepatocytes and appears to be involved in energy metabolism. The aim of this study was to determine plasma LECT2 levels in newly diagnosed type 2 diabetic patients and to correlate the results with various metabolic parameters.A total of 93 newly diagnosed type 2 diabetic patients and 80 age- and sex-matched nondiabetes mellitus ones were enrolled in the study. Plasma LECT2 levels were measured by enzyme-linked immunosorbent assay.Circulating LECT2 levels were approximately 1.3 times higher in newly diagnosed type 2 diabetic patients than in controls (mean 30.30 vs 23.23 ng/mL, P < .001). Correlation analysis showed that LECT2 was negatively associated with high-density lipoprotein-cholesterol (HDL-C) levels in type 2 diabetic patients and obese subjects (P < .05). In multiple stepwise regression analysis, HDL-C, HOMA-IR, BMI, FINS, and TG were significantly independent determinants for LECT2 (P < .05).Our study showed that circulating LECT2 concentrations are significantly higher in newly diagnosed type 2 diabetic patients and further elevated in obese type 2 diabetic patients. LECT2 concentrations are significantly negatively associated with HDL-cholesterol levels in newly diagnosed type 2 diabetic patients and obese subjects.

Type 2 diabetes-related proteins derived from an in vitro model of inflamed fat tissue

Currently, there is a worldwide increase of patients with type 2 diabetes (T2D). During the progression of healthy obese to T2D status, there is an influx of immune cells, in particular macrophages, into visceral adipose tissue, accompanied by an increase of inflammatory cytokines, such as, IL6, TNFα and Hp. To get a better insight in the underlying mechanisms, we performed a quantitative LCMS analysis on a modified in vitro assay, combining 3T3L1 adipocytes and activated RAW264.7 macrophages, thus mimicking inflamed adipose tissue. Clinically known proteins, e.g. IL6, TNFα, AdipoQ, complement factor C3, B and D were identified, thus confirming the assay. In addition, we found 54 new proteins that can potentially be used for research into the mechanism of T2D. Comparison of our results to a study on human visceral fat of obese non-diabetic and obese diabetic subjects, indicated that AUH, NAGK, pCYT2, NNMT, STK39 and CSNK2A2 might indeed be linked to insulin resistance in humans. Moreover, the expression of some of these genes was also altered in human blood samples at early or later stages of insulin desensitization. Overall, we conclude that the direct contact co-culture of 3T3L1 adipocytes with activated macrophages could be a mechanistically relevant and partially translational model of inflamed visceral adipose tissue.

Favourable metabolic profile sustains mitophagy and prevents metabolic abnormalities in metabolically healthy obese individuals

BackgroundObesity-mediated oxidative stress results in mitochondrial dysfunction, which has been implicated in the pathogenesis of metabolic syndrome and T2DM. Recently, mitophagy, a cell-reparative process has emerged as a key facet in maintaining the mitochondrial health, which may contribute to contain the metabolic abnormalities in obese individuals. However, the status of mitophagy in metabolically healthy obese (MHO) and metabolically abnormal diabetic obese (MADO) subjects remains to be elucidated. Hence, the present study aims to unravel the alterations in mitochondrial oxidative stress (MOS) and mitophagy in these subjects.Methods60 subjects including MHNO (metabolically healthy non-obese), MHO and MADO were enrolled as per the Asian criteria for obesity (n = 20 each). Biochemical parameters, MOS indices, transcriptional and translational expression of mitophagy markers (PINK1, PARKIN, MFN2, NIX, LC3-II, and LAMP-2), and transmission electron microscopic (TEM) studies were performed in peripheral blood mononuclear cells.ResultsThe MHO subjects displayed a favorable metabolic profile, despite accompanied by an increased adiposity as compared to the MHNO group; while MADO group exhibited several metabolic abnormalities, inspite of similar body composition as MHO subjects. A progressive rise in the MOS was observed in MHO and MADO subjects as compared to the MHNO group, and it showed a positive and significant correlation with the body composition in these groups. Further, mitophagy remained unaltered in the MHO group, while it was significantly downregulated in the MADO group. In addition, TEM studies revealed a significant increase in the percentage of damaged mitochondria in MADO patients as compared to other groups, while MHO and MHNO groups did not show any significant alterations for the same.ConclusionA favorable metabolic profile and moderate levels of MOS in the MHO group may play a crucial role in the sustenance of mitophagy, which may further limit the aggravation of MOS, inflammation, and emergence of metabolic aberrations in contrast to MADO subjects, who exhibited multiple metabolic abnormalities and attenuated mitophagy. Therefore, these MHO subjects are likely to be at a lower risk of developing metabolic syndrome and T2DM.

Decreased serum microRNA-21 level is associated with obesity in healthy and type 2 diabetic subjects

Background: Recently, much attention has been paid to the role of circulating microRNAs (miRNAs) as novel biomarkers for various diseases. The aim of this study was to investigate the level of a subset of miRNAs in serum samples of the diabetic and healthy subjects.Methods: Forty two healthy and 45 T2D subjects participated in this study. Serum miR-21, miR-126, and miR-146a levels were measured using real-time PCR.Results: There was no significant difference in the serum level of miR-21, miR-126, and miR-146a between the diabetic and non-diabetic groups. The level of miR-21 in obese non-diabetic and diabetic subjects was significantly lower than lean subjects. Correlation analyses in non-diabetic and diabetic groups revealed a significant negative correlation between the amount of miR-21 and body mass index, waist circumference, insulin, and HOMA-IR levels.Conclusions: A reduced level of miR-21 might associate with obesity and its related metabolic traits such as hyperinsulinaemia.

MicroRNA 21 is up-regulated in adipose tissue of obese diabetic subjects.

We investigated miR21 expression in omental (OAT) and subcutaneous adipose tissue (SAT) from 16 obese subjects undergoing bariatric surgery. Patients were divided into two age- and BMI-matched groups according to the presence of type 2 diabetes (T2D). miR21 was not differently expressed in OAT and SAT. However, miR21 expression was two folds greater in adipose tissue in patients with T2D. Accordingly, in primary cultures of adipocytes from non diabetic overweight subjects, miR21 expression increased after 24-h exposure to high glucose and insulin. In conclusion, miR21 appears linked to insulin-resistance deterioration within its pathophysiologic progression from obesity to T2D.

The development of diabetes in obese subjects : the interaction of p53 codon 72 and ACP1

The development of diabetes in obese subjects : the interaction of p53 codon 72 and ACP1

The In-vitro Antimicrobial and Antioxidant Activities of some Diels-Alder Diaryl Methanone Adducts

The in-vitro antimicrobial and antioxidant activities of some 2-(9H-fluorene-2-yl)-3-(substituted phenyl)bicyclo [2.2.1]hept-5-ene-2-yl methanones by disc-diffusion as well as serial dilution against their microbial strains and DPPH radical scavenging activities. The titled substrates were synthesized by environmentally benign water mediated Diels-Alder reaction of 9H-2-fluorenyl chalcones and cyclopentadiene in good yields. Conclusion: The present results confirm the positive correlation between the acute phase response of inflammation and oxidative stress in non-diabetic and diabetic obese subjects.

Response to: Comment on "Differences in Ventilatory Threshold for Exercise Prescription in Outpatient Diabetic and Sarcopenic Obese Subjects".

Response to: Comment on "Differences in Ventilatory Threshold for Exercise Prescription in Outpatient Diabetic and Sarcopenic Obese Subjects".

Comment on "Differences in Ventilatory Threshold for Exercise Prescription in Outpatient Diabetic and Sarcopenic Obese Subjects".

Comment on "Differences in Ventilatory Threshold for Exercise Prescription in Outpatient Diabetic and Sarcopenic Obese Subjects".

Genetic Variation in Leptin Receptor Gene in Diabetic and Non-Diabetic Obese Subjects from Erbil City

There have been numerous genetic causes of obesity specifically leptin, genetic variants of the leptin receptor gene (LEPR Gln223Arg) which appeared to be polymorphismized (A&gt;G; rs1137101) have been implicated in the pathogenesis of obesity in several populations, although no association has been evidenced in other regions in the world. In this study, the association between LEPR Gln223Arg polymorphism with Body Mass Index (BMI) and plasma leptin levels in obese diabetic and obese non-diabetic adults who are randomly selected from Erbil city is evaluated. Blood samples were collected for DNA extraction, and plasma leptin measurements. LEPR (A &gt; G; rs1137101) genotypes were identified by a PCR- RFLP. The results show that plasma leptin concentrations increased with body mass index, and in obese diabetic group was more than two-fold increases p=0.001 when compared to those of obese non-diabetic patients. LEPR (A &gt; G; rs1137101) gene polymorphisms did not found associated with BMI in the whole studied population. Furthermore an increased frequency of the GG genotype in the female control group 32.1 compared to obese group 19.2, but the frequency did not significant (OR= 1.38: 95% CI; 0.74-2.03, P=0.07 ) which indicated that this genotype might be associated with a protective effect against obesity in female only and that this effect was independent of diabetes. Further analysis of a larger population is required to confirm the biological relevance of this polymorphism for obesity in the Kurdish population.

Genetic Variability Within ADA Gene and Susceptibility to Type 2 Diabetes in Obese Subjects

Genetic Variability Within ADA Gene and Susceptibility to Type 2 Diabetes in Obese Subjects

LIRA 365 Plus-A Real World Experience of 19 Months Use of Liraglutide in the Obese Indian Type 2 Diabetic Subjects

Background:Data from Indian sub-continent regarding the safety and efficacy of long term usage (one year and beyond) of liraglutide is scanty. The present study endeavors to share some data from a real world scenario. Aim:To evaluate the effect of liraglutide on body weight, blood pressure and glycemic control in obese Indian type 2 diabetic subjects. Methodology:Single centered, retrospective, real world, observational study conducted on subjects taking liraglutide for a period of 19 months in the endocrine out-patient department. Results:Data of 39 subjects were available for one year and beyond. Mean age was 47.89 ± 11 years. Mean duration of diabetes was 6.46 ± 4.55 years. Glycosylated hemoglobin (HbA1c) significantly decreased from 9.08 ± 1.54% at baseline to 7.26 ± 1.02% at end of therapy. Body weight significantly reduced from 88.27 ± 10.68 kg at baseline to 80.8 ± 11.83 kg at end of therapy and BMI significantly declined from 33.22 ± 4.5 to 31 ± 5.1 at end of therapy respectively. No major adverse effects were reported. Conclusion:In our present study long term liraglutide therapy was associated with significant and sustained reduction in HbA1c and bodyweight. Liraglutide therapy, when tolerated for initial 3-6 months, was associated with minimal gastrointestinal side effects and no gastrointestinal adverse event related drop-out. Liraglutide thus can be a natural choice of second line anti-diabetic agent in the subset of obese diabetic subjects.

Pattern of Glucose and Lipid Profile in Obese Diabetic and Non-diabetic Subjects in the Population of Rawalpindi

Obesity is the fifth leading risk for global deaths, which may lead to type 2 diabetes mellitus. This study was planned to see the glucose and lipid profile in obese diabetic and non-diabetic subjects in the local population of Rawalpindi. We planned to study the variation of glucose and lipid profile in obese diabetic and non-diabetic subjects in the local population of Rawalpindi. This case control study was conducted at chemical pathology Laboratory, Holy Family Hospital and Benazir Bhutto Hospital, Rawalpindi. Non-probability purposive sampling was done on 100 subjects out of whom 50 were obese diabetic (21 males and 29 females), and 50 were obese non diabetic (23 males and 27 females) individuals from the general population of Rawalpindi. Blood sample was analyzed for estimation of FPG (fasting plasma glucose) and lipid profile. The t-test was applied and p-Value of &lt;0.005 was considered significant. The study showed that the FPG of obese diabetics was higher than obese non-diabetic (164.7±29 and 92.9±10.5mg/dl) with a p-Value is &lt;0.001. Total cholesterol was (204.3±17.4 and 161.6±38.1mg/dl) and a p-Value is &lt;0.001. Triglycerides (TG) was (216±34 and 146±57mg/dl) and a p-Value is &lt;0.001. HDL (high density lipoproteins) was (33±3.5 and 38±5.4mg/dl) and a p-Value is &lt;0.001). LDL (low density lipoproteins) was (127±16 and 94±33mg/dl) and a p-Value is &lt;0.001, respectively. No significant difference in BMI (body mass index) was observed between obese Diabetic and non-Diabetics and this was (29.2±6 and 30.3±4.5 kg/m2) and a p-Value is &lt;0.279. It is concluded that difference in the levels of fasting plasma glucose and lipid profile is highly significant in both obese diabetic and non-diabetic individuals.

Targeting hyperapoB by hypocaloric diets to reduce the risks for type 2 diabetes in obese subjects

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)