leptin and Prediabetic-State

Probiotics or synbiotics consumption have been suggested to reduce the risk of cardiovascular disease (CVD) through a decline in inflammation and oxidative stress, however, the results from studies are conflicting. This study filled this knowledge gap by evaluating randomized controlled trials (RCTs) investigating probiotics or synbiotics intake on adipokines, inflammation, and oxidative stress in patients with prediabetes and type-2 diabetes mellitus (T2DM).. We systematically did search up to March 2022 in PubMed/Medline, Scopus, ISI Web of Science, and Cochrane library. A random-effect model was applied to estimate the weighted mean difference (WMD) and 95% confidence interval (95% CI) for each outcome.. A total of 32 RCTs were included in the meta-analysis. This intervention led to a significant decrease in levels of C-reactive protein (CRP) (WMD - 0.62 mg/l; 95% CI - 0.80, - 0.44; p < 0.001), tumor necrosis factor-α (TNF-α) (WMD - 0.27 pg/ml; 95% CI - 0.44, - 0.10; p = 0.002) and malondialdehyde (MDA) (WMD - 0.51 µmol/l; 95% CI - 0.73, - 0.30; p < 0.001), and also a significant increase in levels of glutathione (GSH) (WMD 69.80 µmol/l; 95% CI 33.65, 105.95; p < 0.001), total antioxidant capacity (TAC) (WMD 73.59 mmol/l; 95% CI 33.24, 113.95; p < 0.001) and nitric oxide (NO) (WMD 7.49 µmol/l; 95% CI 3.12, 11.86; p = 0.001), without significant alterations in interleukin-6 (IL-6) and adipokines levels.. A consumption of probiotics or synbiotics could be a useful intervention to improve cardiometabolic outcomes through a reduced inflammation and oxidative stress in patients with prediabetes and T2DM.

Topics: Adipokines; Adiponectin; Diabetes Mellitus, Type 2; Dietary Supplements; Glutathione; Humans; Inflammation; Leptin; Oxidative Stress; Prediabetic State; Probiotics; Randomized Controlled Trials as Topic; Synbiotics

Inflammatory stage in prediabetes is associated with increase in level of adipokines and pro-inflammatory cytokines. Physical activity promotion considered as a first-line therapeutic strategy to treat prediabetes. We have conducted the systematic review and meta-analysis to strengthen the evidence on the impact of physical activity promotion on inflammatory markers in prediabetes.. Studies were identified using electronic search and manual search techniques by choosing keywords for prediabetes, physical activity and inflammatory marker. Randomized controlled trials on individuals diagnosed with prediabetes and provided intervention in the form of physical activity were included in this review. Adiponectin, leptin, C-reactive protein, interleukin-6 and tumour necrosis factor-α were the considered outcome measures.. Our search retrieved 1,688 citations, 31 full-text articles assessed for eligibility of inclusion. Nine studies satisfied the pre-specified criteria for inclusion. Meta-analysis found that physical activity with or without dietary or lifestyle modification reduces level of leptin (MD-2.11 ng/mL, 95% CI -3.81 - -0.42) and interleukin-6 (MD -0.15 pg/mL, 95% CI -0.25--0.04). It has no effect on level of adiponectin (MD 0.26 µg/mL, 95% CI -0.42- 0.93), C-reactive protein (MD -0.05 mg/L, 95% CI -0.33-0.23) and tumour necrosis factor-α (MD 0.67 pg/mL, 95% CI -2.56-3.89).. This review suggests that physical activity promotion with dietary and lifestyle modification may reduce the level of leptin and interleukin-6 but are uncertain if there is any effect on levels of adiponectin, C-reactive protein and tumour necrosis factor-α in the individuals with prediabetes.

Topics: Adipokines; Adiponectin; Adult; Aged; Biomarkers; C-Reactive Protein; Cytokines; Exercise; Female; Humans; Inflammation; Inflammation Mediators; Leptin; Male; Middle Aged; Prediabetic State; Randomized Controlled Trials as Topic; Tumor Necrosis Factor-alpha; Young Adult

Although the state of prediabetes is defined by its role as a diabetes risk factor, it also carries a significant risk of cardiovascular disease, independent of progression to diabetes. Typical diabetic microvascular complications also occur, albeit at low rates, in prediabetes. There is evidence that both glucose-related and glucose-independent mechanisms contribute to these vascular complications. Effective preventive strategies will likely require control of glycemia, as well as other metabolic risk factors. This article reviews some of the proposed mechanisms for the vascular complications of the prediabetic state.

Topics: Adiponectin; Adipose Tissue; Blood Glucose; Cardiovascular Diseases; Diabetes Complications; Endothelium, Vascular; Glucose Intolerance; Humans; Insulin Resistance; Leptin; Obesity; Oxidative Stress; Prediabetic State

Recent studies indicate that glucagon-like peptide (GLP)-1 inhibits appetite in part through regulation of soluble leptin receptors. Thus, during weight loss maintenance, GLP-1 receptor agonist (GLP-1RA) administration may inhibit weight loss-induced increases in soluble leptin receptors thereby preserving free leptin levels and preventing weight regain.. In a randomized controlled trial, 52 healthy obese individuals were, after a diet-induced 12% body weight loss, randomized to treatment with or without administration of the GLP-1RA liraglutide (1.2 mg per day). In case of weight gain, low-calorie diet products were allowed to replace up to two meals per day to achieve equal weight maintenance. Glucose tolerance and hormone responses were investigated before and after weight loss and after 52 weeks weight maintenance. Primary end points: increase in soluble leptin receptor plasma levels and decrease in free leptin index after 52 weeks weight loss maintenance.. Soluble leptin receptor increase was 59% lower; 2.1±0.7 vs 5.1±0.8 ng ml(-1) (-3.0 (95% confidence interval (CI)=-0.5 to -5.5)), P<0.001 and free leptin index decrease was 43% smaller; -62±15 vs -109±20 (-47 (95% CI=-11 to -83)), P<0.05 with administration of GLP-1RA compared with control group. The 12% weight loss was successfully maintained in both the groups with no significant change in weight after 52 weeks follow-up. The GLP-1RA group had greater weight loss during the weight maintenance period (-2.3 kg (95% CI=-0.6 to -4.0)), and had fewer meal replacements per day compared with the control group (minus one meal per day (95% CI=-0.6 to -1)), P<0.001. Fasting glucose was decreased by an additional -0.2±0.1 mmol l(-1) in the GLP-1RA group in contrast to the control group, where glucose increased 0.3±0.1 mmol l(-1) to the level before weight loss (-0.5mmol l(-1) (95% CI=-0.1 to -0.9)), P<0.005. Meal response of peptide PYY3-36 was higher at week 52 in the GLP-1RA group compared with the control group, P<0.05.. The weight maintaining effect of GLP-1RAs may be mediated by smaller decrease in free leptin and higher PYY3-36 response. Low dose GLP-1RA therapy maintained 12% weight loss for 1 year and may prevent pre-diabetes in obesity.

Topics: Adult; Appetite; Body Mass Index; Caloric Restriction; Denmark; Female; Glucagon-Like Peptide-1 Receptor; Humans; Incretins; Leptin; Liraglutide; Male; Obesity; Prediabetic State; Treatment Outcome; Weight Loss

The correlation between total testosterone levels, exercise capacity, and metabolic and echocardiographic parameters was studied in 1097 male subjects with coronary artery disease (CAD) and different stages of glucose tolerance.. Testosterone level was the lowest among diabetics as compared to prediabetics or controls (P < 0.001). Total and abdominal adiposity were the highest in the subjects with the lowest testosterone. Independent of adiposity, fasting glucose, insulin, and leptin were higher (P < 0.03 to < 0.001) among diabetic and control groups in the lowest, and HbA1c values (P < 0.001) higher among diabetics in the lowest, than in the highest testosterone tertile. Controls and prediabetic subjects with the lowest testosterone levels had the lowest HDL-cholesterol levels, and controls also the highest triglycerides. An association between low testosterone level and low maximal exercise capacity was observed in diabetics (P < 0.001) and controls (P < 0.03). Independent of adiposity and metabolic parameters, low testosterone levels were associated with the highest septal wall thickness (P < 0.03) among diabetics.. A negative correlation between low testosterone and dysmetabolic features was observed. Independent of metabolic status, low plasma testosterone seems to be an indicator of impaired maximal exercise capacity and cardiac hypertrophy among CAD patients with type II diabetes.

Topics: Analysis of Variance; Blood Glucose; Body Mass Index; Cholesterol, HDL; Coronary Artery Disease; Diabetes Mellitus, Type 2; Echocardiography, Doppler; Exercise Tolerance; Glycated Hemoglobin; Heart Septum; Humans; Hypertrophy; Insulin; Leptin; Male; Prediabetic State; Testosterone; Triglycerides; Waist Circumference

High-density lipoproteins (HDLs) have antiatherogenic properties related to their chemical structure. Adipose tissue (AT) influences HDL reverse cholesterol transport and plasma HDL cholesterol levels. However, whether AT dysfunction affects HDL subpopulations and their glycation in early type 2 diabetes (T2D) is still unknown.. To investigate the association of inflammation and AT dysfunction serum markers with the size and glycation of HDLs in normoglycemic, prediabetes, and T2D subjects.. We assessed HDL particle size and advanced glycation end-product (AGE) content in HDLs isolated from normoglycemic (n = 17), prediabetes (n = 17), and recently T2D-diagnosed (n = 18) subjects. Insulin, adiponectin, and plasminogen activator inhibitor 1 (PAI-1) were determined using the Bio-Rad Multiplex Platform, and free fatty acids (FFAs) and high sensitivity C-reactive protein (hs-CRP) were determined by standard procedures. The AT insulin resistance (ATIR) index and ATIR/adiponectin and adiponectin/leptin ratios were calculated.. HDL was progressively smaller (nm) and enriched with AGE (mg-BSA-AGE/mg protein) according to the glucose categories: 8.49 and 7.5 in normoglycemic subjects, 8.44 and 12.4 in prediabetic subjects, and 8.32 and 14.3 in T2D subjects (P = 0.033 and P = 0.009 for size and AGE, respectively). In multivariable regression analysis, the ATIR/adiponectin ratio was inversely associated with HDL size (β = -0.257, P = 0.046), and the ATIR ratio was directly associated with HDL glycation (β = 0.387, P = 0.036). In contrast, adiponectin and the adiponectin/leptin ratio were not associated with alterations in HDL particles. Furthermore, HDL size was associated with resistin (β = -0.348, P = 0.007) and PAI-1 (β = -0.324, P = 0.004). HDL and AGE were related to insulin concentrations (β = 0.458, P = 0.015). Analyses were adjusted for age, sex, body mass index, triglycerides, and HDL-cholesterol.. HDL size was significantly associated with the ATIR/adiponectin ratio and inflammation, whereas glycation was more strongly related to the ATIR index. These findings have important implications for the management and prevention of cardiovascular disease in T2D patients.

Topics: Adiponectin; Adipose Tissue; Biomarkers; Cholesterol, HDL; Diabetes Mellitus, Type 2; Glycation End Products, Advanced; Humans; Insulin; Leptin; Lipoproteins, HDL; Maillard Reaction; Plasminogen Activator Inhibitor 1; Prediabetic State

Leptin plays a key role in the regulation of body weight and other endocrine systems. Recently, impairment of leptin gene transcription due to genetic variations in a long noncoding RNA (lncOb) has been described. This retrospective study aims to characterize the clinical and metabolic phenotype of children and adolescents with obesity who were homozygous for the lncOb rs10487505 leptin lowering allele.. Enrolled children underwent an anthropometrical evaluation, biochemical assessment, and genotyping for lncOb rs10487505. Plasma leptin levels were assessed in 150 participants. A total of 434 patients were included and divided into two groups according to rs10487505 recessive inheritance (CC vs. GG/GC).. Children who were homozygous for the C allele showed higher fasting insulin (p = 0.01), homeostasis model assessment of insulin resistance (p = 0.01), lower whole-body insulin sensitivity index (p = 0.02), and lower disposition index (p = 0.03). Moreover, CC patients presented with a higher prevalence of prediabetes (9.3% vs. 3.4%, p = 0.04) and a 2.9-fold (95% CI: 1.1-7.9, p = 0.04) higher risk of prediabetes compared with G-carriers independently from confounders. Leptin plasma levels were significantly lower in the CC group (p = 0.002). Hormone levels correlated with BMI z score (r = 0.19, p = 0.04), fasting insulin (r = -0.34, p < 0.0001), homeostasis model assessment of insulin resistance (r = -0.33, p < 0.0001), and disposition index (r = 0.20, p = 0.04).. The lncOb rs10487505 polymorphism affects leptin circulating levels, worsens insulin resistance, and heightens the risk of prediabetes in children and adolescents with obesity.

Topics: Adolescent; Body Mass Index; Child; Glucose; Humans; Insulin; Insulin Resistance; Leptin; Pediatric Obesity; Prediabetic State; Retrospective Studies

Recently, we proposed two pathophysiologic subtypes of type 2 diabetes mellitus (T2DM), one related and one unrelated to metabolic syndrome. To begin to understand the pathophysiology of the subtype unrelated to metabolic syndrome, we now measured selected hormones and signaling molecules in affected individuals. In this cross-sectional analysis, we examined 138 women out of the monocenter, post gestational diabetes study PPSDiab. Of these women, 73 had prediabetes or screening-diagnosed T2DM, 40 related to metabolic syndrome and 33 unrelated. The remaining 65 women were normoglycemic controls. Our analysis included medical history, anthropometrics, oral glucose tolerance testing, laboratory chemistry, and cardiopulmonary exercise testing. In addition, plasma proinsulin/insulin ratio, growth hormone (hGH) nadir during oral glucose tolerance testing, Insulin-like Growth Factor I (IGF-I), Leptin, Resistin, Adiponectin, Fetuin-a, FGF21, and myostatin were measured. Compared to controls, women with prediabetes or screening-diagnosed T2DM unrelated to metabolic syndrome depicted higher plasma Leptin [10.47(6.6-14.57) vs. 5.52(3.15-10.02); p<0.0001] and IGF-I [193.01(171.00-213.30) vs. 167.97(138.77-200.64); p=0.0008], as well as a lower hGH nadir [0.07(0.05-0.15) vs. 0.14(0.08-0.22; p<0.0001]. These differences were independent of body adiposity. Women with prediabetes or T2DM related to metabolic syndrome, in comparison to controls, displayed elevated Leptin, Fetuin-a, and FGF21, as well as reduced Adiponectin and hGH nadir. Based on our study, altered Leptin and hGH/IGF-I signaling could potentially contribute to the pathophysiology of prediabetes and T2DM unrelated to metabolic syndrome. Further mechanistic investigations of these signaling pathways in the context of lean T2DM are necessary to test causal relationships.

Topics: Adiponectin; alpha-2-HS-Glycoprotein; Body Mass Index; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Diabetes, Gestational; Female; Humans; Insulin-Like Growth Factor I; Leptin; Metabolic Syndrome; Prediabetic State; Pregnancy

Background and Objectives: It has been confirmed that adiponectin/leptin (A/L) ratio correlates better with cardiometabolic risk factors than hormone levels alone. The aim of our study was to determine the risk of developing post-transplant diabetes mellitus (PTDM) and other metabolic conditions depending on A/L ratio after kidney transplantation (KT). Material and Methods: In a prospective analysis, the studied samples were divided into three groups: control group, prediabetes and PTDM group. Pre-transplantation, at 3, 6 and 12 months after KT, we recorded basic characteristics of donor and recipient. We also monitored levels of adipocytokines and calculated A/L ratio. Results: During observed period, we recorded significant increase in A/L ratio in control group (p = 0.0013), on the contrary, a significant decrease in PTDM group (p = 0.0003). Using Cox regression Hazard model, we identified age at time of KT (HR 2.8226, p = 0.0225), triglycerides at 1 year (HR 3.5735, p = 0.0174) and A/L ratio < 0.5 as independent risk factors for prediabetes and PTDM 1-year post-transplant (HR 3.1724, p = 0.0114). Conclusions: This is the first study to evaluate the relationship between A/L and risk of PTDM and associated metabolic states after KT. We found out that A/L ratio <0.5 is independent risk factor for prediabetes and PTDM 1 year post-transplant.

Topics: Adiponectin; Diabetes Mellitus; Humans; Kidney Transplantation; Leptin; Postoperative Complications; Prediabetic State

Background The prognostic value of anthropometric, adipokine, and computed tomography measures of adiposity to predict diabetes in Black, specifically by normoglycemia versus prediabetes, remains incompletely understood. Methods and Results Among Black participants without diabetes in the JHS (Jackson Heart Study), waist circumference [WC], body mass index, adiponectin, leptin, and leptin:adiponectin ratio were standardized in sample 1 (2422 participants at baseline [2000-2004]) and WC, body mass index, visceral adipose tissue (VAT), subcutaneous adipose tissue, and liver attenuation in 1537 participants at examination 2 (2005-2008) (sample 2). Hazard ratios (HRs) for diabetes were estimated using interval-censored Cox modeling adjusting for traditional risk factors and validated with the C index. Over 5 years, 300 and 122 incident diabetes cases occurred in sample 1 and sample 2, respectively. In sample 1 and sample 2, a 1-SD higher log-leptin:adiponectin ratio and VAT had the strongest associations (HR, 1.95 [95% CI, 1.67-2.27] and 1.76 [95% CI, 1.52-2.04]) and discriminatory power (C index 0.68 [95% CI, 0.64-0.71] and C index 0.67 [95% CI, 0.61-0.74]) with diabetes. The normoglycemic compared with the prediabetes group had a 1.3 to 1.9 times greater magnitude of associations with diabetes for WC, liver attenuation, and VAT (

Topics: Adiponectin; Adiposity; Adult; Body Mass Index; Diabetes Mellitus; Humans; Intra-Abdominal Fat; Leptin; Longitudinal Studies; Obesity; Prediabetic State; Risk Factors; Waist Circumference

Prediabetes is a strong predictor of type 2 diabetes and its associated cardiovascular complications, but few studies explore sexual dimorphism in this context. Here, we aim to determine whether sex influences physiological response to high-fat high-sucrose diet (HFS) and myocardial tolerance to ischemia-reperfusion injury. Male and female Wistar rats were subjected to standard (CTRL) or HFS diet for 5 months. Then, ex-vivo experiments on isolated perfused heart model were performed to evaluate tolerance to ischemia-reperfusion injury. HFS diet induced fasting hyperglycemia and increased body fat percent to a similar level in both sexes. However, glucose intolerance was more pronounced in female HFS. Cholesterol was increased only in female while male displayed higher level of plasmatic leptin. We observed increased heart weight to tibia length ratio only in males, but we showed a similar decrease in tolerance to ischemia-reperfusion injury in female and male HFS compared with respective controls, characterized by impaired cardiac function, energy metabolism and coronary flow during reperfusion. In conclusion, as soon as glucose intolerance and hyperglycemia develop, we observe higher sensitivity of hearts to ischemia-reperfusion injury without difference between males and females.

Topics: Animals; Cholesterol; Diabetes Mellitus, Type 2; Diet, High-Fat; Dietary Sucrose; Energy Metabolism; Female; Glucose Intolerance; Humans; Hyperglycemia; Leptin; Male; Myocardial Reperfusion Injury; Myocardium; Oxidative Stress; Prediabetic State; Rats; Rats, Wistar; Sex Factors; Weight Gain

The impact of diet and fibre fractions on adipocytokines in obese subjects with a risk of diabetes has not been investigated in detail yet. The purpose of the study is to evaluate the effects of a 12-month lifestyle intervention with different fibre profiles (resistant starch (RS)-rich fibre, or ordinary food fibre profiles) on adipocytokine levels. Fifty participants are divided into two groups (RS group and Fibre group). The groups differ only in the percentage of the recommended level of the RS consumed as a fraction of the same total fibre amount. The applied dietary intervention includes intake of 7531 KJ/daywith a total fibre portion of 25-35 g/dayfor both groups that includes 15 g/day of RS for the RS group only. The levels of leptin, adiponectin, apelin, resistin, tumor necrosis factor (TNF)-alpha and C-reactive protein (CRP) are measured, and their relationship to anthropometric and biochemical parameters is estimated. Along with significant body weight loss, only leptin is significantly reduced by 13% in the RS group while in the Fibre group, apelin levels are significant (-21%). Polynomial regression shows a negative correlation between RS intake and adiponectin (R2 = 0.145) and resistin level (R2 = 0.461) in the RS group. This study indicates the possibility that fibre fractions differently influence the outcome of lifestyle interventions, as well as their adipocytokine levels, in obese prediabetic adults.

Topics: Adipokines; Adiponectin; Aged; Apelin; Biomarkers; Diet; Dietary Fiber; Exercise; Humans; Inflammation; Leptin; Life Style; Male; Middle Aged; Obesity; Prediabetic State; Resistant Starch; Resistin; Weight Loss

Prediabetes is associated with a high risk of colon cancer, and abdominal obesity, which can result in the secretion of several obesity-related adipocytokines, is an independent influencing factor for colonic polyps in prediabetes subjects. However, the correlation between adipocytokine levels and colonic polyps in prediabetes subjects is unclear. This research explores the relationship between plasma adiponectin, visfatin, leptin, and resistin levels and the development of colonic polyps in prediabetes subjects.. A total of 468 prediabetes subjects who underwent electronic colonoscopy examinations were enrolled in this study; there were 248 cases of colonic polyps and 220 cases without colonic mucosal lesions. Then, colonic polyps patients with prediabetes were subdivided into a single-polyp group, multiple-polyps group, low-risk polyps group, or high-risk polyps group. In addition, 108 subjects with normal glucose tolerance who were frequency matched with prediabetes subjects by sex and age were selected as the control group; 46 control subjects had polyps, and 62 control subjects were polyp-free. Plasma adiponectin, visfatin, leptin, and resistin levels were measured in all the subjects, and the related risk factors of colonic polyps in prediabetes subjects were analysed.. Plasma adiponectin levels were significantly lower in the polyps group than in the polyp-free group [normal glucose tolerance (9.8 ± 4.8 vs 13.3 ± 3.9) mg/L, P = 0.013; prediabetes (5.6 ± 3.7 vs 9.2 ± 4.4) mg/L, P = 0.007]. In prediabetes subjects, plasma adiponectin levels were decreased significantly in the multiple polyps group [(4.3 ± 2.6 vs 6.7 ± 3.9) mg/L, P = 0.031] and the high-risk polyps group [(3.7 ± 2.9 vs 7.4 ± 3.5) mg/L, P < 0.001] compared to their control groups. Plasma visfatin levels were higher in the polyps group and the multiple-polyps group than those in their control groups (P = 0.041 and 0.042, respectively), and no significant difference in plasma leptin and resistin levels was observed between these three pairs of groups (all P > 0.05). The multivariate logistic regression analysis showed that lower levels of plasma adiponectin was a risk factor for colonic polyps, multiple colonic polyps, and high-risk colonic polyps in prediabetes subjects.. Plasma adiponectin levels are inversely associated with colonic polyps, multiple colonic polyps, and high-risk colonic polyps in prediabetes subjects. And adiponectin may be involved in the development of colon tumours in prediabetes subjects.

Topics: Adenomatous Polyps; Adiponectin; Adult; Aged; Case-Control Studies; China; Colonic Polyps; Colonoscopy; Colorectal Neoplasms; Cytokines; Female; Humans; Leptin; Male; Middle Aged; Neoplasms, Multiple Primary; Nicotinamide Phosphoribosyltransferase; Prediabetic State; Resistin; Risk Factors

Evidences support the view that central obesity is an independently cardiovascular risk. It is thought that leptin contributes to autonomic dysfunction and cardiovascular risks in type 1 and type 2 diabetes mellitus (T1DM and T2DM). This raises the possibility that leptin might mediate the relationship between central obesity and the severity of cardiovascular autonomic neuropathy (CAN) in patients with well-controlled T2DM and prediabetes.. The complete cardiovascular reflex tests and biomarkers were assessed for each patient. The severity of CAN was assessed using composite autonomic scoring scale (CASS). A single-level three-variable mediation model was used to investigate the possible relationships among central obesity [as indicated by waist circumference (WC)], leptin level, and severity of CAN (as indicated by CASS value).. A total of 107 patients were included in this study: 90 with diabetes and 17 with prediabetes. The results demonstrate that increased WC is associated with increased severity of CAN (r = 0.242, P = 0.017). We further discovered that leptin level is positively correlated with WC (r = 0.504, P < 0.0001) and the CASS value (r = 0.36, P < 0.0001). Further mediation analysis shows that leptin level serves as mediators between higher WC and higher CASS.. Our results highlighted the relationship among leptin, central obesity, and severity of CAN. As the leptin level serves as mediator between central obesity and severity of CAN, a longitudinal study is needed to confirm that control of WC can decrease leptin levels and can be effective in reducing CAN progression.

Topics: Body Mass Index; Diabetes Mellitus, Type 2; Humans; Leptin; Longitudinal Studies; Obesity, Abdominal; Prediabetic State; Risk Factors; Waist Circumference

Pericoronary adipose tissue inflammation might lead to the development and destabilization of coronary plaques in prediabetic patients. Here, we evaluated inflammation and leptin to adiponectin ratio in pericoronary fat from patients subjected to coronary artery bypass grafting (CABG) for acute myocardial infarction (AMI). Furthermore, we compared the 12-month prognosis of prediabetic patients compared to normoglycemic patients (NG). Finally, the effect of metformin therapy on pericoronary fat inflammation and 12-months prognosis in AMI-prediabetic patients was also evaluated.. An observational prospective study was conducted on patients with first AMI referred for CABG. Participants were divided in prediabetic and NG-patients. Prediabetic patients were divided in two groups; never-metformin-users and current-metformin-users receiving metformin therapy for almost 6 months before CABG. During the by-pass procedure on epicardial coronary portion, the pericoronary fat was removed from the surrounding stenosis area. The primary endpoints were the assessments of Major-Adverse-Cardiac-Events (MACE) at 12-month follow-up. Moreover, inflammatory tone was evaluated by measuring pericoronary fat levels of tumor necrosis factor-α (TNF-α), sirtuin 6 (SIRT6), and leptin to adiponectin ratio. Finally, inflammatory tone was correlated to the MACE during the 12-months follow-up.. The MACE was 9.1% in all prediabetic patients and 3% in NG-patients. In prediabetic patients, current-metformin-users presented a significantly lower rate of MACE compared to prediabetic patients never-metformin-users. In addition, prediabetic patients showed higher inflammatory tone and leptin to adiponectin ratio in pericoronary fat compared to NG-patients (P < 0.001). Prediabetic never-metformin-users showed higher inflammatory tone and leptin to adiponectin ratio in pericoronary fat compared to current-metformin-users (P < 0.001). Remarkably, inflammatory tone and leptin to adiponectin ratio was significantly related to the MACE during the 12-months follow-up.. Prediabetes increase inflammatory burden in pericoronary adipose tissue. Metformin by reducing inflammatory tone and leptin to adiponectin ratio in pericoronary fat may improve prognosis in prediabetic patients with AMI. Trial registration Clinical Trial NCT03360981, Retrospectively Registered 7 January 2018.

Topics: Adiponectin; Adipose Tissue; Aged; Biomarkers; Coronary Artery Bypass; Female; Humans; Hypoglycemic Agents; Inflammation Mediators; Italy; Leptin; Male; Metformin; Middle Aged; Myocardial Infarction; Prediabetic State; Prospective Studies; Risk Factors; Sirtuins; Time Factors; Treatment Outcome; Tumor Necrosis Factor-alpha

Food contains bioactive compounds that may prevent changes in gut microbiota associated with Westernized diets. The aim of this study is to explore the possible additive effects of D-fagomine and ω-3 PUFAs (EPA/DHA 1:1) on gut microbiota and related risk factors during early stages in the development of fat-induced pre-diabetes. Male Sprague Dawley (SD) rats were fed a standard diet, or a high-fat (HF) diet supplemented with D-fagomine, EPA/DHA 1:1, a combination of both, or neither, for 24 weeks. The variables measured were fasting glucose and glucose tolerance, plasma insulin, liver inflammation, fecal/cecal gut bacterial subgroups and short-chain fatty acids (SCFAs). The animals supplemented with D-fagomine alone and in combination with ω-3 PUFAs accumulated less fat than those in the non-supplemented HF group and those given only ω-3 PUFAs. The combined supplements attenuated the high-fat-induced incipient insulin resistance (IR), and liver inflammation, while increasing the cecal content, the Bacteroidetes:Firmicutes ratio and the populations of Bifidobacteriales. The functional effects of the combination of D-fagomine and EPA/DHA 1:1 against gut dysbiosis and the very early metabolic alterations induced by a high-fat diet are mainly those of D-fagomine complemented by the anti-inflammatory action of ω-3 PUFAs.

Topics: Animals; Blood Glucose; Diet, High-Fat; Drug Therapy, Combination; Fatty Acids, Omega-3; Gastrointestinal Microbiome; Glucose Tolerance Test; Imino Pyranoses; Insulin; Leptin; Male; Prediabetic State; Rats; Rats, Sprague-Dawley; Risk Factors

Bone mineral density (BMD) and fracture risk are elevated in adults with impaired fasting glucose (IFG) or type 2 diabetes mellitus (T2D). This study aimed to compare bone health among Inuit women with IFG, T2D and normoglycemia. The study included Inuit women (≥40 y) with IFG (n = 57), T2D (n = 72) or normoglycemia (n = 340) from the International Polar Year Inuit Health Survey 2007-2008 in Canada. Distal one-third forearm BMD (FaBMD) was measured using a peripheral instantaneous x-ray imager. Anthropometry, fasting plasma glucose (FPG), serum adiponectin, leptin and 25-hydroxyvitamin D (25(OH)D) were measured. Traditional food intakes were surveyed. Data were analysed using mixed model ANOVA and regression models. The median age was 53 (IFG: IQR 48, 67) y and 56 (T2D: IQR 49, 63) y. Compared to normoglycemic women, FaBMD and T-scores were significantly lower in women with T2D, but not with IFG. Frequency of marine mammal intakes (ß = 0.145; 95%CI: 0.018, 0.053, p = 0.0001) positively related to FaBMD. The odds ratio of having a T-score consistent with osteoporosis was lower among women with T2D and higher BMI, while aging increased the risk. Although T2D associates with lower BMD among Inuit women, risk of osteoporosis is tempered, possibly by maintenance of a traditional lifestyle.

Topics: Adiponectin; Adult; Aged; Blood Glucose; Body Weights and Measures; Bone Density; Canada; Diabetes Mellitus, Type 2; Female; Forearm; Health Behavior; Health Status; Humans; Inuit; Leptin; Middle Aged; Prediabetic State; Vitamin D

Background In the last decade, there has been an increased interest toward fat tissue as an endocrine organ that secretes many cytokines and bioactive mediators that play a role in insulin sensitivity, inflammation, coagulation and the pathogenesis of atherosclerosis. The aim of this study was to investigate classical (adiponectin, leptin, resistin) and new (chemerin, vaspin, omentin) adipocytokine levels in subjects with prediabetes [impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT)] and obese subjects with normoglycemia. Methods In this study, 80 patients with a mean age of 50.4 ± 10.6 years were recruited, divided into two groups with similar age and body mass index (BMI) - with obesity and normoglycemia (n = 41) and with obesity and prediabetes (n = 39). Results Serum adiponectin levels were significantly higher in subjects with normoglycemia compared to patients with prediabetes. Adiponectin has a good discriminating power to distinguish between patients with and without insulin resistance in our study population [area under the curve (AUC) = 0.728, p = 0.002]. Other adipocytokine levels were not significantly different between the two groups. The patients with metabolic syndrome (MetS) had significantly lower levels of leptin compared to those without MetS (33.03 ± 14.94 vs. 40.24 ± 12.23 ng/mL) and this difference persisted after adjustment for weight and BMI. Receiver operating characteristic (ROC) analysis showed that low serum leptin can predict the presence of MetS (p = 0.03), AUC = 0.645. Conclusion Serum adiponectin is statistically higher in patients with normoglycemia compared to those with prediabetes and has a predictive value for distinguishing between patients with and without insulin resistance in the studied population. Serum leptin has a good predictive value for distinguishing between patients with and without MetS in the studied population.

Topics: Adipokines; Adiponectin; Adipose Tissue; Adult; Aged; Blood Glucose; Body Mass Index; Chemokines; Female; Humans; Insulin Resistance; Intercellular Signaling Peptides and Proteins; Leptin; Male; Middle Aged; Prediabetic State; Resistin; ROC Curve

Gestational diabetes mellitus is a significant risk factor for metabolic syndrome and cardiovascular disease.. To assess the relationships between components of the metabolic syndrome and cytokine and adhesion molecule levels in women with GDM during pregnancy and after delivery.. A prospective case-control study on a sample of 126 pregnant women (63 with and 63 without gestational diabetes mellitus). In an intra-subject analysis, 41 women with history of gestational diabetes mellitus and 21 controls were re-assessed in the postpartum period. Clinical data and levels of cytokines and adhesion molecules were recorded during weeks 24-29 of pregnancy and 12 months after delivery.. In the postpartum period, there were significantly higher levels of tumor necrosis factor alpha in both cases and controls, and of adiponectin in controls. Cases showed higher leptin levels, with no significant differences during and after pregnancy. No significant differences were seen in adhesion molecules and interleukin-6 between cases and controls during pregnancy and in the postpartum period, but levels of both were higher in cases. During pregnancy and after delivery, adiponectin decreased in cases and increased in controls. Significant positive correlations were seen between adiponectin and fasting blood glucose levels and vascular cell adhesion molecule-1, and also between leptin and tumor necrosis factor alpha levels.. The results suggest that increased inflammation and transient hyperglycemia during pregnancy would represent a latent form of metabolic syndrome, with an increased risk for type 2 diabetes mellitus and future cardiovascular disease.

Topics: Adiponectin; Adult; Blood Glucose; Cardiovascular Diseases; Case-Control Studies; Cell Adhesion Molecules; Cytokines; Diabetes, Gestational; Disease Susceptibility; Female; Humans; Hyperglycemia; Inflammation; Leptin; Metabolic Syndrome; Postpartum Period; Prediabetic State; Pregnancy; Prospective Studies; Tumor Necrosis Factor-alpha; Young Adult

This study explores the determinants of sex hormone binding globulin (SHBG) and associations with categories of glucose intolerance and undiagnosed diabetes in first-degree relatives (FDR) of patients with Type 2 Diabetes Mellitus (T2D).. Anthropometric indices, fasting lipids, glucose, insulin, adiponectin, leptin, SHBG, estradiol (E2), testosterone (TT), androstenedione (AND), dehydroepiandrosterone sulphate (DHEA-S), high-sensitivity C-reactive protein (hs-CRP) and alanine aminotransferase (ALT) were measured in 584 FDR. Homeostasis model assessment-estimate of insulin resistance (HOMA-IR), beta cell function (%B), insulin sensitivity (%S) and free androgen index (FAI) were calculated.. 266 subjects were normoglycemic; 237 had prediabetes and 81 had undiagnosed diabetes. SHBG decreased stepwise with worsening categories of glucose intolerance in females whereas FAI decreased stepwise with worsening categories in males only. SHBG showed significant positive correlations with adiponectin, and HDL-C and significant negative correlations with body mass index (BMI), waist circumference (WC), Waist:hip ratio (WHR), ALT, triglycerides (TG), %B, leptin and FAI. After adjustment for WHR, only HDL-C and FAI in men and FAI and HbA1c in females remained significantly associated with SHBG. Receiver Operating Characteristic (ROC) curve analysis for detection of diabetes showed that areas under the curve for FAI and SHBG were 0.711 and 0.386 for males and 0.430 and 0.660 for females respectively.. Associations of SHBG with some anthropometric and metabolic variables in FDR suggests that lower levels is a marker for risk of developing T2D through obesity dependent metabolic pathways but low FAI is a better marker of state of diabetes in males.

Topics: Adiponectin; Adult; Biomarkers; Body Mass Index; C-Reactive Protein; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Female; Humans; Insulin; Insulin Resistance; Leptin; Male; Middle Aged; Prediabetic State; ROC Curve; Sex Hormone-Binding Globulin; Triglycerides; Waist Circumference; Young Adult

Diabetes is a growing health care issue, and prediabetes has been established as a risk factor for type 2 diabetes. Prediabetes is characterized by deregulated glucose control, and elucidating pathways which govern this process is critical. We have identified the wild-type (WT) p53-inducible phosphatase (WIP1) phosphatase as a regulator of glucose homeostasis. Initial characterization of insulin signaling in WIP1 knockout (WIP1(KO)) murine embryo fibroblasts demonstrated reduced insulin-mediated Ak mouse transforming activation. In order to assess the role of WIP1 in glucose homeostasis, we performed metabolic analysis on mice on a low-fat chow diet (LFD) and high fat diet (HFD). We observed increased expression of proinflammatory cytokines in WIP1(KO) murine embryo fibroblasts, and WIP1(KO) mice fed a LFD and a HFD. WIP1(KO) mice exhibited glucose intolerance and insulin intolerance on a LFD and HFD. However, the effects of WIP1 deficiency cause different metabolic defects in mice on a LFD and a HFD. WIP1(KO) mice on a LFD develop hepatic insulin resistance, whereas this is not observed in HFD-fed mice. Mouse body weights and food consumption increase slightly over time in LFD-fed WT and WIP1(KO) mice. Leptin levels are increased in LFD-fed WIP1(KO) mice, compared with WT. In contrast, HFD-fed WIP1(KO) mice are resistant to HFD-induced obesity, have decreased levels of food consumption, and decreased leptin levels compared with HFD-WT mice. WIP1 has been shown to regulate the nuclear factor kappa-light-chain-enhancer of activated B cells pathway, loss of which leads to increased inflammation. We propose that this increased inflammation triggers insulin resistance in WIP1(KO) mice on LFD and HFD.

Topics: Animals; Cells, Cultured; Diabetes Mellitus, Type 2; Diet, Fat-Restricted; Diet, High-Fat; Dietary Fats; Fibroblasts; Genetic Predisposition to Disease; Glucose; Glucose Intolerance; Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating); Insulin; Insulin Resistance; Interleukin-6; Leptin; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Obesity; Phosphoprotein Phosphatases; Prediabetic State; Primary Cell Culture; Protein Phosphatase 2C; Signal Transduction; Tumor Necrosis Factor-alpha

Adipose tissue-derived hormone leptin plays a functional role in glucose tolerance through its effects on insulin secretion and insulin sensitivity which also represent the risk factors for nonalcoholic fatty liver disease (NAFLD). The present study explored the gender specific association of serum leptin and insulinemic indices with NAFLD in Bangladeshi prediabetic subjects. Under a cross-sectional analytical design a total of 110 ultrasound examined prediabetic subjects, aged 25-68 years consisting of 57.3% male (55.6% non NAFLD and 44.4% NAFLD) and 42.7% female (57.4% non NAFLD and 42.6% NAFLD), were investigated. Insulin secretory function (HOMA%B) and insulin sensitivity (HOMA%S) were calculated from homeostasis model assessment (HOMA). Serum leptin showed significant positive correlation with fasting insulin (r = 0.530, P = 0.004), postprandial insulin (r = 0.384, P = 0.042) and HOMA-IR (r = 0.541, P = 0.003) as well as significant negative correlation with HOMA%S (r = -0.388, P = 0.046) and HOMA%B (r = -0.356, P = 0.039) in male prediabetic subjects with NAFLD. In multiple linear regression analysis, log transformed leptin showed significant positive association with HOMA-IR (β = 0.706, P <0.001) after adjusting the effects of body mass index (BMI), triglyceride (TG) and HOMA%B in male subjects with NAFLD. In binary logistic regression analysis, only log leptin [OR 1.29 95% (C.I) (1.11-1.51), P = 0.001] in male subjects as well as HOMA%B [OR 0.94 95% (C.I) (0.89-0.98), P = 0.012], HOMA-IR [OR 3.30 95% (C.I) (0.99-10.95), P = 0.049] and log leptin [OR 1.10 95% (C.I) (1.01-1.20), P = 0.026] in female subjects were found to be independent determinants of NAFLD after adjusting the BMI and TG. Serum leptin seems to have an association with NAFLD both in male and female prediabetic subjects and this association in turn, is mediated by insulin secretory dysfunction and insulin resistance among these subjects.

Topics: Adiposity; Adult; Aged; Anthropometry; Bangladesh; Body Mass Index; Cross-Sectional Studies; Female; Homeostasis; Humans; Insulin; Insulin Secretion; Leptin; Linear Models; Male; Middle Aged; Non-alcoholic Fatty Liver Disease; Postprandial Period; Prediabetic State; Risk Factors; Sex Factors; Triglycerides; Ultrasonography

The obesity-related hormones leptin and adiponectin are independently and oppositely associated with insulin resistance, which is an important risk factor for coronary artery disease (CAD) and restenosis after coronary intervention. In this report, we set out to determine the role of the leptin-adiponectin ratio (LAR) in non-diabetic patients with or without impaired glucose tolerance undergoing a percutaneous coronary intervention.. 300 PCI patients were enrolled in this prospective single-centre study. Patients with known diagnosis of diabetes (n = 50) and newly diagnosed diabetes (2h OGTT > 200 mg/dL, n = 25) were excluded. In both stable and acute subjects, assessment was done on the day of discharge and included a fasting glucose level, leptin, adiponectin and an oral glucose tolerance test (OGTT).. LAR was significantly higher in diabetic (7.2 ± 0.7) than in non-diabetic patients (3.9 ± 0.3, P = 0.001), and even higher in newly diagnosed diabetics (9.8 ± 1.5, P < 0.001). Likewise, among non-diabetic patients, LAR was significantly higher in patients with impaired glucose tolerance. LAR was significantly higher in pre-diabetic (4.57 ± 0.48) versus normoglycaemic patients (3.45 ± 0.33, P = 0.05). LAR was found to be numerically higher in pre-diabetic versus normoglycaemic patients with two- and three-vessel disease (VD), but not in patients with single VD. In pre-diabetic patients, LAR was found to be significantly increased with more advanced CAD (P = 0.021), independent of stable versus unstable presentation.. LAR is related to the extent of CAD in pre-diabetic patients but not in normoglycaemic patients. This finding might in part explain the poorer outcome in revascularized patients with impaired glucose tolerance compared to normoglycaemic patients.

Topics: Adiponectin; Aged; Biomarkers; Blood Glucose; Coronary Angiography; Coronary Artery Disease; Enzyme-Linked Immunosorbent Assay; Female; Follow-Up Studies; Humans; Leptin; Male; Middle Aged; Percutaneous Coronary Intervention; Prediabetic State; Preoperative Period; Prospective Studies; Risk Factors

Soy isoflavones have received great attention for their beneficial effects on health and disease, i.e., in patients with diabetes. Equol is a biologically active isoflavone-related metabolite with interindividual differences in its production. The current study investigated the relationship between an equol-producing state and the levels of adipocytokine markers in a prediabetic and diabetic population.. A total of 79 subjects (34 males/45 females) in a prediabetic or diabetic state recruited from the general population were examined regarding their ability to produce equol using urine samples. Clinical data, such as age, smoking as well as anthropometric and biochemical variables, including body mass index (BMI), lipids, insulin, glucose, hemoglobin A1c, leptin and adiponectin, were recorded.. Equol producers exhibited lower leptin and leptin/BMI than non-producers among females. Simple correlation tests and stepwise multiple regression analyses revealed a significant inverse correlation between the leptin/BMI and equol-production. This relationship was not found in males.. Female equol producers can have favorable metabolic traits in relation to leptin metabolism in this population. Further studies are needed to confirm these results.

Topics: Adiponectin; Age Factors; Blood Glucose; Body Mass Index; Cross-Sectional Studies; Diabetes Mellitus; Equol; Female; Glycated Hemoglobin; Humans; Insulin; Intestinal Mucosa; Intestines; Isoflavones; Leptin; Lipids; Male; Prediabetic State; Sampling Studies; Sex Characteristics; Smoking; Soy Foods

High fat programming, by exposure to a high saturated fat diet during fetal and/or lactational life induces metabolic derangements and alters islet cell architecture in neonate and weanling rats.. The present study assessed metabolic changes and islet cell dynamics in response to high fat maintenance during specific developmental periods in adolescent rats, with some parameters also studied in neonate and weanling rats.. The experimental groups comprised neonates, weanlings and adolescents maintained on a high fat diet during specific periods of fetal, lactational and/or postnatal life. Control neonates, weanlings and adolescents were maintained on a standard laboratory (control or low fat) diet. Fetal high fat programmed (i.e., maintained on a high fat diet exclusively during fetal life) neonates were insulin resistant.. Weanlings maintained on a high fat diet throughout fetal and lactational life had increased pancreas weights. Fetal high fat programmed adolescents presented a normal phenotype mimicking the control adolescents. Adolescents maintained on a postnatal high fat diet had increased body weights, hyperglycemia, hyperinsulinemia, hyperleptinemia and insulin resistance displaying beta cell hypertrophy and increased islet cell proliferation. Adolescents maintained on a fetal and postnatal high fat diet had increased body weights, hyperleptinemia, hyperinsulinemia and insulin resistance.. High fat programming induces various diabetogenic phenotypes which present at different life stages. The postnatal period from birth to adolescence represents an extension for high fat programming of metabolic disease.

Topics: Acinar Cells; Age Factors; Animals; Animals, Newborn; Animals, Suckling; Blood Glucose; Cell Proliferation; Dietary Fats; Fatty Acids; Female; Hyperglycemia; Hyperinsulinism; Insulin Resistance; Insulin-Secreting Cells; Lactation; Leptin; Organ Size; Prediabetic State; Pregnancy; Rats, Wistar; Weaning

Lactation may influence future progression to type 2 diabetes after gestational diabetes mellitus (GDM). However, biomarkers associated with progression to glucose intolerance have not been examined in relation to lactation intensity among postpartum women with previous GDM. This study investigates whether higher lactation intensity is related to more favorable blood lipids, lipoproteins and adipokines after GDM pregnancy independent of obesity, socio-demographics and insulin resistance.. The Study of Women, Infant Feeding, and Type 2 Diabetes (SWIFT) is a prospective cohort study that recruited 1035 women diagnosed with GDM by the 3-h 100g oral glucose tolerance tests (OGTTs) after delivery of a live birth in 2008-2011. Research staff conducted 2-h 75 g OGTTs, and assessed lactation intensity, anthropometry, lifestyle behaviors and socio-demographics at 6-9 weeks postpartum (baseline). We assayed fasting plasma lipids, lipoproteins, non-esterified free fatty acids, leptin and adiponectin from stored samples obtained at 6-9 weeks postpartum in 1007 of the SWIFT participants who were free of diabetes at baseline. Mean biomarker concentrations were compared among lactation intensity groups using multivariable linear regression models.. Increasing lactation intensity showed graded monotonic associations with fully adjusted mean biomarkers: 5%-8% higher high-density lipoprotein cholesterol (HDL-cholesterol), 20%-28% lower fasting triglycerides, 15%-21% lower leptin (all trend P-values < 0.01), and with 6% lower adiponectin, but only after adjustment for insulin resistance (trend P-value = 0.04).. Higher lactation intensity was associated with more favorable biomarkers for type 2 diabetes, except for lower plasma adiponectin, after GDM delivery. Long-term follow-up studies are needed to assess whether these effects of lactation persist to predict progression to glucose intolerance.

Topics: Adiponectin; Adult; Biomarkers; Cohort Studies; Diabetes Mellitus, Type 2; Diabetes, Gestational; Disease Progression; Fatty Acids, Nonesterified; Female; Humans; Insulin Resistance; Lactation; Leptin; Lipids; Lipoproteins; Middle Aged; Postpartum Period; Prediabetic State; Pregnancy; Young Adult

Most Swedish studies show stable diabetes prevalence despite increasing obesity, but glucose levels may shift upwards below the diagnostic threshold for diabetes. Our aim was to explore trends in glucose distribution in northern Sweden; whether these trends were uniformly distributed throughout the spectrum of glucose concentrations; and to relate trends to traditional risk factors and the obesity-related adipokine leptin.. The project consisted of four cross-sectional surveys between 1990 and 2009, with 7069 participants aged 25-64 years. The overall participation rate was 74.4%. Trend analyses of glucose concentrations along the entire distribution and linear regression in relation to survey years and risk markers were used.. Fasting and post-load glucose increased in women (both P < 0.001) and post-load glucose in men (P = 0.004). The increase was seen in most deciles of glucose concentrations. The prevalence of impaired glucose tolerance doubled in women to 14.5% and tripled in men to 10.1% (both P = 0.004). The prevalence of impaired fasting glucose rose in women from 4.5 to 7.7% (P < 0.001). The prevalence of diabetes was unchanged-6.4% in 2009. In men, leptin, together with traditional risk factors, explained 7.8 and 10.8% of the variance in fasting (P = 0.008) and post-load (P < 0.001) glucose, respectively.. Increasing fasting and post-load glucose concentrations were seen in most deciles of the glucose distribution, indicating a shift in the entire population. Leptin was significantly associated with fasting and post-load glucose in men.

Topics: Adult; Biomarkers; Blood Glucose; Cohort Studies; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Fasting; Female; Glucose Intolerance; Glucose Tolerance Test; Health Surveys; Health Transition; Humans; Leptin; Male; Middle Aged; Models, Biological; Prediabetic State; Prevalence; Risk Factors; Sex Factors; Sweden

Perfluorooctane sulfonate (PFOS), which belongs to the degradation product of many perfluorinated compounds, is on the list of persistent organic pollutants (POPs) and is currently detected in both wildlife and humans. The consequence of gestational and lactational exposure to PFOS on prediabetes effect in offspring was investigated in rats in the present study. Maternal rats were treated with vehicle, 0.5 mg/kg/day or 1.5 mg/kg/day PFOS respectively from gestation day 0 to postnatal day 21. The glucose and lipid metabolism effects were investigated on the offspring in adulthood. The gestational and lactational exposure to PFOS led to low body weight from birth to weaning, and evoked signs of a prediabetic state, with elevated fasting serum insulin and leptin level, impaired glucose tolerance, though the fasting serum glucose and glycosylated serum protein level were normal. Abnormal lipid homeostasis was also observed by the phenomenon of hepatic steatosis and increased gonadal fat pad weight. However, the circulating serum level of fasting triglyceride and cholesterol level were no different from controls. Our results suggested that developmental exposure to PFOS may contribute to glucose and lipid metabolic disorder in adulthood.

Topics: Adipose Tissue; Alkanesulfonic Acids; Animals; Animals, Newborn; Environmental Pollutants; Fatty Liver; Female; Fluorocarbons; Glucose; Glucose Intolerance; Homeostasis; Insulin; Lactation; Leptin; Lipid Metabolism; Male; Maternal Exposure; Prediabetic State; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Rats, Wistar; Triglycerides; Weight Gain

Insulin clearance may decline as an early mechanism compensating for deteriorating insulin sensitivity. However, no previous studies have investigated the association between subclinical inflammation or impaired fibrinolysis and insulin clearance. We examined the association between plasminogen activator inhibitor (PAI)-1, C-reactive protein (CRP), TNF-α, leptin and fibrinogen and the progression of metabolic clearance rate of insulin (MCRI) over time.. We studied 784 non-diabetic white, Hispanic and African-American individuals in the Insulin Resistance Atherosclerosis Study (IRAS). Insulin sensitivity, acute insulin response and MCRI were determined from frequently sampled intravenous glucose tolerance tests at baseline and at 5-year follow-up. Inflammatory and fibrinolytic proteins were measured in fasting plasma at baseline.. MCRI had declined significantly by 29% at the 5-year follow-up. We observed a significant association between higher plasma PAI-1 levels and the decline in MCRI in multivariable-adjusted regression models (β = -0.045 [95% CI -0.081, -0.0091]). Higher plasma CRP and leptin levels were associated with a decline in MCRI in unadjusted models, but these associations were non-significant after adjusting for BMI and waist circumference (β = -0.016 [95% CI -0.041, 0.0083] for CRP; β = -0.044 [95% CI -0.10, 0.011] for leptin). A higher plasma TNF-α concentration was associated with a decline in MCRI in unadjusted (β = -0.071 [95% CI -0.14, -0.00087]) but not in multivariable-adjusted (β = -0.056 [95% CI -0.13, 0.017]) models. Plasma fibrinogen level was not associated with the change in MCRI.. We identified that higher plasma PAI-1 (but not CRP, TNF-α, leptin or fibrinogen) levels independently predicted the progressive decline of insulin clearance in the multiethnic cohort of the IRAS.

Topics: Atherosclerosis; Body Mass Index; Cohort Studies; Diabetic Angiopathies; Female; Fibrinogen; Follow-Up Studies; Humans; Hypoglycemic Agents; Inflammation Mediators; Insulin; Insulin Resistance; Leptin; Male; Metabolic Clearance Rate; Middle Aged; Overweight; Plasminogen Activator Inhibitor 1; Prediabetic State; Prospective Studies; Risk Factors; United States

Prediabetes (PreDM) in asymptomatic adults is associated with abnormal circadian blood pressure variability (abnormal CBPV).. Systemic inflammation and glycemia influence circadian blood pressure variability.. Dahl salt-sensitive (S) rats (n = 19) after weaning were fed either an American (AD) or a standard (SD) diet. The AD (high-glycemic-index, high-fat) simulated customary human diet, provided daily overabundant calories which over time lead to body weight gain. The SD (low-glycemic-index, low-fat) mirrored desirable balanced human diet for maintaining body weight. Body weight and serum concentrations for fasting glucose (FG), adipokines (leptin and adiponectin), and proinflammatory cytokines [monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor-α (TNF-α)] were measured. Rats were surgically implanted with C40 transmitters and blood pressure (BP-both systolic; SBP and diastolic; DBP) and heart rate (HR) were recorded by telemetry every 5 minutes during both sleep (day) and active (night) periods. Pulse pressure (PP) was calculated (PP = SBP-DBP).. [mean(SEM)]: The AD fed group displayed significant increase in body weight (after 90 days; p < 0.01). Fasting glucose, adipokine (leptin and adiponectin) concentrations significantly increased (at 90 and 172 days; all p < 0.05), along with a trend for increased concentrations of systemic pro-inflammatory cytokines (MCP-1 and TNF-α) on day 90. The AD fed group, with significantly higher FG, also exhibited significantly elevated circadian (24-hour) overall mean SBP, DBP, PP and HR (all p < 0.05).. These data validate our stated hypothesis that systemic inflammation and glycemia influence circadian blood pressure variability. This study, for the first time, demonstrates a cause and effect relationship between caloric excess, enhanced systemic inflammation, dysglycemia, loss of blood pressure control and abnormal CBPV. Our results provide the fundamental basis for examining the relationship between dysglycemia and perturbation of the underlying mechanisms (adipose tissue dysfunction induced local and systemic inflammation, insulin resistance and alteration of adipose tissue precursors for the renin-aldosterone-angiotensin system) which generate abnormal CBPV.

Topics: Adiponectin; Animals; Biomarkers; Blood Glucose; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Chemokine CCL2; Circadian Rhythm; Diet, High-Fat; Disease Models, Animal; Heart Rate; Inflammation; Inflammation Mediators; Leptin; Prediabetic State; Rats; Rats, Inbred Dahl; Telemetry; Time Factors; Tumor Necrosis Factor-alpha; Weight Gain

This study investigated the associations of plasma leptin levels with insulin resistance (IR) and prediabetes in relatively lean, rural Chinese men and women.. This study included 574 subjects aged 21-45 years from a community-based twin cohort. Plasma leptin concentrations were measured by sandwich immunoassays using flowmetric xMAP technology. Prediabetes was defined based on fasting plasma glucose and 75-g oral glucose tolerance test. Multivariate linear and logistic regression analyses were used to investigate gender-specific associations of leptin with IR measures and prediabetes, adjusting for intra-twin correlation, measures of adiposity, and other pertinent covariates.. The body mass index is 22.3+/-2.7 kg/m(2) in men and 22.5+/-2.7 kg/m(2) in women. Leptin levels were positively associated with IR. Individuals with higher tertiles of leptin also had increased risk of prediabetes with odds ratios (OR) of 2.6 (95% confidence interval (CI): 1.4-5.1) and 4.3 (95% CI: 2.1-8.7) in men; OR of 1.1 (95% CI: 0.6-2.1) and 3.1 (95% CI 1.5-6.2) in women for second and third tertile respectively. These associations were attenuated after further adjusting for adiposity measurements only in men. The leptin-prediabetes associations disappeared after adjusting for the homeostatic model assessment of IR in both genders.. In this sample of relatively lean rural Chinese adults, plasma leptin levels were associated with IR and prediabetes in a dose-response fashion, which were not totally explained by adiposity. Our data emphasize that prediabetes is not all about obesity, and leptin may be an additional biomarker for screening individuals at high risk for prediabetes in this population.

Topics: Adult; Asian People; Body Mass Index; Female; Humans; Insulin Resistance; Leptin; Logistic Models; Male; Middle Aged; Motor Activity; Obesity; Odds Ratio; Prediabetic State; Risk Factors; Sex Factors

In the nontransplant setting diabetes mellitus is a risk factor for disease progression in patients with chronic hepatitis C virus (HCV) infection. The impact of early insulin resistance on the development of advanced fibrosis, even in the absence of clinically apparent diabetes mellitus, is not known. Our aim was to determine whether the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) can be used to identify insulin-resistant patients at risk for rapid fibrosis progression. Cohort study including patients transplanted for chronic HCV between January 1, 1995 and January 1, 2005. One hundred sixty patients were included; 25 patients (16%) were treated for diabetes mellitus and 36 patients (23%) were prediabetic, defined as HOMA-IR >2.5. Multivariate Cox regression analysis showed that insulin resistance (hazard ratio (HR) 2.07; confidence interval (CI) 1.10-3.91, p = 0.024), donor age (HR 1.33;CI 1.08-1.63, p = 0.007) and aspartate aminotransferase (HR 1.03;CI 1.01-1.05, p < 0.001) were significantly associated with a higher probability of developing advanced fibrosis, i.e. Knodell fibrosis stage 3 or 4, whereas steatosis (HR 0.94;CI 0.46-1.92, p = 0.87) and acute cellular rejection (HR 1.72;CI 0.88-3.36, p = 0.111) were not. In conclusion, posttransplant insulin resistance is strongly associated with more severe recurrence of HCV infection. HOMA-IR is an important tool for the identification of insulin resistance among patients at risk for rapid fibrosis progression after liver transplantation for HCV.

Topics: Adipokines; Adult; Cohort Studies; Diabetes Complications; Disease Progression; Female; Hepatitis C, Chronic; Humans; Insulin Resistance; Kaplan-Meier Estimate; Leptin; Liver Cirrhosis; Liver Transplantation; Male; Middle Aged; Prediabetic State; Regression Analysis; Risk

Little information is available on leptin concentrations in individuals with IGT. This study aims to determine and correlate leptin levels to anthropometric measures of obesity in pre-diabetic, (IFG and IGT), type 2 diabetic and normoglycaemic Saudis.. 308 adult Saudis (healthy controls n = 80; pre-diabetes n = 86; Type 2 diabetes n = 142) participated. Anthropometric parameters were measured and fasting blood samples taken. Serum insulin was analysed, using a solid phase enzyme amplified sensitivity immunoassay and also leptin concentrations, using radio-immunoassay. The remaining blood parameters were determined using standard laboratory procedures.. Leptin levels of diabetic and pre-diabetic men were higher than in normoglycaemic men (12.4 [3.2-72] vs 3.9 [0.8-20.0] ng/mL, (median [interquartile range], p = 0.0001). In females, leptin levels were significantly higher in pre-diabetic subjects (14.09 [2.8-44.4] ng/mL) than in normoglycaemic subjects (10.2 [0.25-34.8] ng/mL) (p = 0.046). After adjustment for BMI and gender, hip circumference was associated with log leptin (p = 0.006 with R2 = 0.086) among all subjects.. Leptin is associated with measures of adiposity, hip circumference in particular, in the non-diabetic state among Saudi subjects. The higher leptin level among diabetics and pre-diabetics is not related to differences in anthropometric measures of obesity.

Topics: Adiposity; Adult; Aged; Anthropometry; Body Mass Index; Diabetes Mellitus, Type 2; Female; Humans; Leptin; Male; Middle Aged; Obesity; Prediabetic State; Saudi Arabia

Hyperleptinemia, associated with prediabetes, is an independent risk factor for coronary artery disease and a mediator of coronary endothelial dysfunction. We previously demonstrated that acutely raising the leptin concentration to levels comparable with those observed in human obesity significantly attenuates coronary dilation/relaxation to acetylcholine (ACh) both in vivo in anesthetized dogs and in vitro in isolated canine coronary rings. Accordingly, the purpose of this investigation was to extend these studies to a model of prediabetes with chronic hyperleptinemia. In the present investigation, experiments were conducted on control and high-fat-fed dogs. High-fat feeding caused a significant increase (131%) in plasma leptin concentration. Furthermore, in high-fat-fed dogs, exogenous leptin did not significantly alter vascular responses to ACh in vivo or in vitro. Coronary vasodilator responses to ACh (0.3-30.0 microg/min) and sodium nitroprusside (1.0-100.0 microg/min) were not significantly different from those observed in control dogs. Also, high-fat feeding did not induce a switch to an endothelium-derived hyperpolarizing factor as a major mediator of muscarinic coronary vasodilation, because dilation to ACh was abolished by combined pretreatment with N(omega)-nitro-l-arginine methyl ester (150 microg/min ic) and indomethacin (10 mg/kg iv). Quantitative, real-time PCR revealed no significant difference in coronary artery leptin receptor gene expression between control and high-fat-fed dogs. In conclusion, high-fat feeding induces resistance to the coronary vascular effects of leptin, and this represents an early protective adaptation against endothelial dysfunction. The resistance is not due to altered endothelium-dependent or -independent coronary dilation, increased endothelium-derived hyperpolarizing factor, or changes in coronary leptin receptor mRNA levels.

Topics: Adaptation, Physiological; Anesthesia; Animals; Coronary Circulation; Coronary Vessels; Dietary Fats; Disease Models, Animal; Dogs; Endothelium, Vascular; Leptin; Male; Obesity; Prediabetic State; RNA, Messenger

The pathophysiology of TallyHo mouse, a recently established animal model for type 2 diabetes mellitus, was analyzed at prediabetic state to examine the inherent defects which contribute to the development of diabetes. At 4 weeks of age, the TallyHo mice already revealed glucose intolerance while their peripheral tissues exhibited normal insulin sensitivity. On the other hand, decreased plasma insulin concentration was observed with little differences in pancreatic insulin contents, indicating the impaired insulin secretion. Such defect, however, was not found in the isolated islets, which suggests a role of endocrine factor in impaired insulin secretion of TallyHo mice. Treatment of leptin inhibited the glucose-stimulated insulin secretion from the isolated islets of TallyHo mice, while in vivo administration of anti-leptin antibody lowered plasma glucose concentration with increased insulin level in TallyHo mice. Expression of glucokinase mRNA was decreased both in whole pancreas and leptin treated islets of TallyHo mice compared with whole pancreas in C57BL/6 mice and untreated islets of TallyHo mice, respectively. These results suggest that elevated plasma leptin can, through the inhibition of insulin secretion, induce glucose intolerance in TallyHo mice.

Topics: Animals; Blood Glucose; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Disease Models, Animal; Glucokinase; Glucose Intolerance; Insulin; Insulin Secretion; Islets of Langerhans; Leptin; Male; Mice; Mice, Inbred C57BL; Mice, Inbred Strains; Pancreas; Prediabetic State; Receptors, Cell Surface; Receptors, Leptin

Leptin has been shown to activate AMP-activated protein kinase (AMPK), an enzyme that regulates the activities of key enzymes of lipid synthesis and metabolism. We assess here (i) whether AMPK activity is diminished in rodents deficient in leptin or the leptin receptor, and (ii) the effects of treating the diabetes-prone, leptin-receptor-deficient Zucker Diabetic Fatty (ZDF) rat with an AMPK activator.. AMPK activity and related parameters were measured in muscle and or liver of fa/fa and ZDF rats and ob/ob mice. We also explored the effect of treatment with the AMPK activator 5-aminoimidazole 4-carboxamide 1-beta-D ribofuranoside (AICAR) (7.4 mmol/l, on Monday, Wednesday and Friday for 15 weeks, beginning at 7 weeks of age) on the phenotype of the ZDF rat.. AMPK activity was diminished in muscle and/or liver of fa/fa (leptin-receptor-deficient, non-diabetic) and ZDF (leptin-receptor-deficient, diabetes-prone) rats and ob/ob mice (leptin-deficient). ZDF rats that had free access to food became hyperglycaemic (22.2 mmol/l) and hyperphagic after 2 to 5 weeks and remained so during the remainder of the study. Treatment of ZDF rats with AICAR prevented the development of diabetes, as well as increases of triglyceride content in liver, muscle and the pancreatic islets. It also attenuated the morphological abnormalities observed in the islets of untreated rats. Rats diet-matched with the AICAR-treated animals developed diabetes of intermediate severity and showed decreases in triglyceride content in the islets, but not in liver or muscle.. The results indicate that a deficiency of leptin or the leptin receptor is associated with a decrease in AMPK activity in muscle and/or liver. They also suggest that treatment with an AMPK activator prevents the development of diabetes and ectopic lipid accumulation in the ZDF rat.

Topics: Adenylate Kinase; Aminoimidazole Carboxamide; Animals; Diabetes Mellitus; Diglycerides; Enzyme Activation; Homozygote; Leptin; Lipid Metabolism; Male; Malonyl Coenzyme A; Mice; Mice, Obese; Prediabetic State; Rats; Rats, Mutant Strains; Rats, Zucker; Ribonucleotides

Ghrelin, leptin and adiponectin are three hormones which are frequently associated with metabolism, obesity and appetite. Recently, it has been shown that they may possess other physiologic roles, specially in connection with the circulation. Ghrelin infusion increases forearm blood-flow in a dose-dependent manner. Leptin has been shown to be involved not only in thermogenesis but angiogenesis as well. Adiponectin, apart from its insulin-sensitizing action, appears to modulate inflammation by inhibiting monocyte adhesion to endothelial cells. Six monkeys, which had been classified as being in the pre-diabetic state, where administered a triglyceride lowering regimen. Microvascular function was assessed using a laser Doppler flow-meter during a temperature provocation test. Percent change in flow from baseline following temperature elevation, as well as percent change in flow/degree rise in temperature were used to evaluate microvascular reserve and reactivity. Using univariate analysis, it appears that increased perfusion is significantly correlated with adiponectin, followed by leptin. Flow was also positively correlated with ghrelin, but the relationship did not attain significance. As expected, flow was also negatively and significantly correlated with fibrinogen. Trends show that flow was also negatively correlated to circulating triglyceride levels (p=0.08). The data indicate that the three hormones appear to possess microvascular actions that may impact on their other physiologic functions.

Topics: Adiponectin; Animals; Blood Glucose; Fibrinogen; Ghrelin; Hyperglycemia; Hyperinsulinism; Hypertriglyceridemia; Hypolipidemic Agents; Intercellular Signaling Peptides and Proteins; Leptin; Macaca mulatta; Metabolic Syndrome; Microcirculation; Obesity; Peptide Hormones; Prediabetic State; Proteins

We reported that the lipoapoptosis of beta-cells observed in fat-laden islets of obese fa/fa Zucker Diabetic Fatty (ZDF) rats results from overproduction of ceramide, an initiator of the apoptotic cascade and is induced by long-chain fatty acids (FA). Whereas the ceramide of cytokine-induced apoptosis may be derived from sphingomyelin hydrolysis, FA-induced ceramide overproduction seems to be derived from FA. We therefore semiquantified mRNA of serine palmitoyltransferase (SPT), which catalyzes the first step in ceramide synthesis. It was 2-3-fold higher in fa/fa islets than in +/+ controls. [3H]Ceramide formation from [3H]serine was 2.2-4. 5-fold higher in fa/fa islets. Triacsin-C, which blocks palmitoyl-CoA synthesis, and L-cycloserine, which blocks SPT activity, completely blocked [3H]ceramide formation from [3H]serine. Islets of fa/fa rats are unresponsive to the lipopenic action of leptin, which normally depletes fat and prevents FA up-regulation of SPT. To determine the role of leptin unresponsiveness in the SPT overexpression, we transferred wild type OB-Rb cDNA to their islets; now leptin completely blocked the exaggerated FA-induced increase of SPT mRNA while reducing the fat content. Beta-cell lipoapoptosis was partially prevented in vivo by treating prediabetic ZDF rats with L-cycloserine for 2 weeks. Ceramide content and DNA fragmentation both declined 40-50%. We conclude that lipoapoptosis of ZDF rats is mediated by enhanced ceramide synthesis from FA and that blockade by SPT inhibitors prevents lipoapoptosis.

Topics: Acyltransferases; Animals; Apoptosis; Ceramides; Diabetes Mellitus, Experimental; Fatty Acids; Gene Expression Regulation; Islets of Langerhans; Leptin; Lipid Metabolism; Male; Obesity; Prediabetic State; Proteins; Rats; Rats, Zucker; RNA, Messenger; Serine; Serine C-Palmitoyltransferase

Overaccumulation of fat in pancreatic islets of obese ZDF fa/fa rats is believed to cause beta-cell failure and diabetes. Previously, we demonstrated that ZDF islets have an increased capacity to esterify fatty acids imported via the circulation. Here we examine the capacity of ZDF islets to synthesize fatty acids de novo. Compared with age-matched wild-type (+/+) control islets, acetyl CoA carboxylase (ACC) mRNA was fivefold and sixfold higher and fatty acid synthetase (FAS) was fourfold and sevenfold higher in prediabetic and diabetic ZDF islets, respectively. Incorporation of label from [14C]glucose into lipids was 84% higher in ZDF islets and was not suppressed normally by fatty acids. Chronic hyperleptinemia, induced by adenoviral transfer of leptin cDNA, reduced ACC and FAS mRNA in +/+ islets by 93 and 80%, respectively, but did not decrease the high ACC and FAS expression in islets of fa/fa rats. Recombinant leptin cultured with islets isolated from +/+ rats lowered ACC and FAS expression by 66 and 47%, respectively, but had no effect in fa/fa islets. We conclude that de novo lipogenesis in islets is controlled by leptin and remains low in leptin-responsive islets. It is increased in leptin-insensitive fa/fa islets, contributing to the fat overload that leads to beta-cell dysfunction and diabetes.

Topics: Acetyl-CoA Carboxylase; Animals; Diabetes Mellitus; Fatty Acid Synthases; Fatty Acids, Nonesterified; Female; Gene Expression; Gene Expression Regulation, Enzymologic; Glucose; Islets of Langerhans; Leptin; Lipids; Male; Obesity; Prediabetic State; Proteins; Rats; Rats, Zucker; Recombinant Fusion Proteins; RNA, Messenger