Search

Background: The aim of this study is to assess for the change in progression of inflammatory, adiposity, and atherosclerotic markers in first degree relatives of type 2 diabetes mellitus patients. Methods: Normal glucose tolerant (NGT) individuals (20–40 years) who had positive family history of T2DM (FHP) were enrolled in this prospective study based on ADA 2015 criteria. Age, sex, and BMI matched controls without any history of diabetes in their parents referred as family history negative (FHN) were taken for comparison. At baseline, detailed clinical assessment and requisite blood/imaging investigations were done. All the available subjects from the original cohort (FHN-32 and FHP-46) were studied after 2 years with recording of the clinical, biochemical and imaging parameters. Results: A total of 64 cases (FHP) and 42 controls (FHN) were enrolled at baseline. FHP group had significantly higher hsCRP (p = 0.039) and cIMT (p = 0.003) than that of FHN group. No significant difference in the rate of conversion of NGT to prediabetes (using multiple criteria) was found after 2 years between the two groups. cIMT was increased significantly from baseline in FHP group than FHN group at the end of the study(0.02 ± 0.03 vs. 0.01 ± 0.02 mm, p = 0.002). But there was no significant difference for changes in glycemic status, lipid parameters, HOMA IR, hsCRP, and adiposity markers between the two groups at the end of the study. Conclusion: Despite no significant differences in change in glycemic parameters or rates of conversion from NGT to pre diabetes, cIMT increased significantly in the normoglycemic offspring of T2DM subjects than those without history of T2DM in their parents. [ABSTRACT FROM AUTHOR]

Purpose: Insulin resistance (IR) is closely associated with lipid accumulation. Here, we investigated the temporal relationship between the two conditions after bariatric surgery. Materials and Methods: In total, 409 participants were enrolled from three bariatric centers in China from 2009 to 2018. We evaluated whether baseline IR (proxied by homeostasis model assessment of insulin resistance (HOMA-IR)) and lipid accumulation (proxied by visceral adiposity index (VAI) and lipid accumulation product (LAP)) were associated with follow-up IR and lipid accumulation (3 months postoperatively) using linear regression models. We then conducted a cross-lagged panel analysis model to simultaneously examine the bidirectional relationship between IR and lipid accumulation. Results: Multivariable linear regression analyses showed that baseline HOMA-IR was associated with follow-up VAI (β = 0.430, 95% CI: 0.082–0.778, p = 0.016) and LAP (β = 0.070, 95% CI: 0.010–0.130, p = 0.022). There was no relationship between baseline lipid accumulation and follow-up IR. Further cross-lagged panel analyses indicated that the path coefficient from baseline HOMA-IR to follow-up VAI (β2 = 0.145, p = 0.003) was significantly greater than the coefficient from baseline VAI to follow-up HOMA-IR (β1 = − 0.013, p = 0.777). Similarly, the path coefficient from baseline HOMA-IR to follow-up LAP (β2 = 0.141, p = 0.003) was significantly greater than the coefficient from baseline LAP to follow-up HOMA-IR (β1 = 0.041, p = 0.391). Conclusion: Our study demonstrated a unidirectional relationship from HOMA-IR to VAI and LAP, suggesting that the change in IR may precede lipid accumulation after surgery. [ABSTRACT FROM AUTHOR]

Purpose: To examine the associations of healthy dietary patterns with cardiometabolic biomarkers and all-cause mortality among individuals with prediabetes. Methods: This cohort study included 8363 adults with prediabetes from the National Health and Nutrition Examination Survey 1999–2014. Healthy dietary patterns including Alternate Healthy Eating Index-2010 (AHEI-2010), Alternate Mediterranean Diet score (AMED), Dietary Approaches to Stop Hypertension score (DASH), and Healthy Eating Index-2015 (HEI-2015) were calculated based on 24-h dietary recall data. Mortality status was obtained by linkage to National Death Index records. Cardiometabolic biomarkers, including blood glucose, insulin, HbA1c, C-reactive protein (CRP), and lipids, were measured at recruitment. Results: During 61,991 person-years of follow-up, 991 deaths occurred. Comparing the extreme quartiles, the multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause mortality were 0.65 (0.49, 0.85) for AHEI-2010 (P-trend = 0.002), 0.68 (0.50, 0.92) for AMED (P-trend = 0.004), 0.72 (0.53, 0.98) for DASH (P-trend = 0.03), and 0.78 (0.58, 1.05) for HEI-2015 (P-trend = 0.08). Besides, the HRs (95% CIs) for all-cause mortality per 20-percentile increment in scores were 0.78 (0.67, 0.90) for AHEI-2010 (P = 0.001), 0.73 (0.62, 0.86) for AMED (P < 0.001), 0.84 (0.69, 1.02) for DASH (P = 0.08), and 0.86 (0.74, 1.00) for HEI-2015 (P = 0.04). In addition, higher dietary scores were associated with favorable blood glucose, insulin, HOMA-IR, blood lipids, and CRP (all P-trend < 0.05). The high-density lipoprotein cholesterol and CRP explained 1.53–9.21% of the associations between dietary patterns and all-cause mortality (P < 0.05). Conclusions: Diets with higher AHEI-2010, AMED, DASH, and HEI-2015 were associated with improved cardiometabolic factors and lower all-cause mortality among individuals with prediabetes. These findings suggest that multiple healthy dietary patterns instead of a one-size-fits-all diet plan might be beneficial and acceptable for individuals with prediabetes. [ABSTRACT FROM AUTHOR]

Background /purpose: Leptin—a protein hormone that plays vital role in the regulation of glucose homeostasis and insulin sensitivity, involved in regulating the circadian rhythms of gonadotropic, thyrotropic and adrenal axes in the endocrine system. This cross-sectional study was undertaken to correlate serum leptin levels and other demographic and biochemical parameters between prediabetic cases and control subjects of Kashmiri population. Furthermore, association of serum leptin levels with various demographic and biochemical parameters along with insulin resistance in pre-diabetic subjects was elucidated. In our study, pre-diabetic cases (n = 212) and healthy controls (n = 196) were enrolled. Methods: All study subjects underwent anthropometric assessment. Serum samples of all study subjects were analysed for biochemical parameters employing the principle of spectrophotometry and leptin levels using sandwich enzyme-linked immunosorbent assay (ELISA). Insulin levels of prediabetic cases were deduced by chemiluminescent micro particle immunoassay (CMIA) technology and thereby calculating their insulin resistance. Results: The cases had statistically increased leptin levels, lipid profile and obesity as compared to controls (p ≤ 0.05). Our study, showed a positive correlation between elevated leptin levels and increased lipid levels (total cholesterol, triglycerides; TG and very low density lipoproteins-cholesterol; VLDL-C) in prediabetics (p < 0.001). Conclusion: Beyond adiposity, leptin levels may increase the risk of pre-diabetes in Kashmiri population. Since the secretion, estimation and measurements of leptins are modest in contrast to insulin levels; therefore, leptin levels can also be included in the routine measurement as an indicator of metabolic syndrome and/or T2DM. [ABSTRACT FROM AUTHOR]

Purpose: The current study aimed to investigate the effects of legumes inclusion in the hypocaloric dietary approaches to stop hypertension (DASH) diet on fasting plasma glucose (FPG) and cardiometabolic risk factors in overweight and obese patients with type 2 diabetes over 16 weeks. Also, the modulatory effects of rs7903146 variant in the transcription factor 7 like 2 (TCF7L2) gene that is associated with the risk of diabetes, were assessed on these cardiometabolic risk factors. Methods: This study was a randomized controlled trial. Three-hundred participants, aged 30–65 years, whose TCF7L2 rs7903146 genotype was determined, were studied. The participants were randomly assigned to receive either the hypocaloric DASH diet or a hypocaloric legume-based DASH diet. The primary outcome was the difference in FPG change from baseline until the 16-week follow-up between the two dietary interventions. The secondary outcomes were differences in insulin resistance and lipid profile changes between the dietary intervention diets. Results: A reduction in FPG, insulin, homeostatic model assessment for insulin resistance (HOMA-IR), triglyceride, total cholesterol, and low-density lipoprotein cholesterol (LDL-C) was observed at week 16 in both hypocaloric dietary interventions. Compared to the DASH diet, the legume-based DASH diet decreased the FPG and HOMA-IR. There is no interaction between rs7903146 and intervention diets on glycemic parameters. Conclusion: The DASH diet, enrich in legumes, could improve the glycemic parameters in participants with type 2 diabetes, regardless of having rs7903146 risk or non-risk allele. Registration number of Clinical Trial: Iranian Registry of Clinical Trials (IRCT) (code: IRCT20090203001640N17). [ABSTRACT FROM AUTHOR]

Background: This cross-sectional research was undertaken to determine the serum levels of asprosin, a novel white adipose tissue-derived glucogenic adipokine, in epileptic patients on valproic acid treatment. Methods: Sixty-six patients diagnosed with idiopathic tonic–clonic generalized epilepsy were divided into three groups: those treated with valproic acid (n = 22), those treated with lamotrigine (n = 22), and twenty-two newly diagnosed or untreated patients. A control group was twenty-two, healthy volunteers with a similar distribution of gender and age. Body mass index (BMI) and fasting serum levels of asprosin, glucose, glycohemoglobin (HbA1c), insulin, and lipid profile were measured for both patients and control groups. Additionally, homeostasis model assessment for insulin resistance (HOMA-IR) was also calculated for the investigated groups. Results: The mean BMI values and fasting serum levels of glucose, HbA1c, insulin, total cholesterol, low-density lipoprotein cholesterol (LDL-C), and triglyceride were much higher in subjects treated with valproic acid than those in the other study groups. Furthermore, a higher number of participants in the valproic acid group fulfilled the insulin resistance criterion (defined as HOMA-IR > 2.5) compared with those in other study groups. The mean fasting serum asprosin concentration was also significantly higher in the valproic acid group than in other study groups. This was while the values of the study parameters were comparable in the healthy, un-treated, and lamotrigine groups. Conclusions: Our finding suggested that elevated asprosin level might be one of the pathological mechanisms involved in the development of obesity, insulin resistance, and metabolic disturbances related to valproic acid treatment. [ABSTRACT FROM AUTHOR]

Purpose: Human sirtuins can be a powerful therapeutic target in preventing and treating obesity and age-related diseases. Some dietary components can modulate sirtuins' activity, such as resveratrol. This systematic review aimed to assess whether resveratrol (RSV), without other interventions, can stimulate sirtuins in the treatment of excess weight and its comorbidities. Methods: MEDLINE/Pubmed, EMBASE and Cochrane Central Register of Controlled Trials (CENTRAL) were used for search eligible articles. Randomized clinical trials assessing RSV supplementation on changes in the sirtuins' gene expression/protein levels was the primary outcome. Other possible changes in cardiometabolic markers were considered the second outcome. Following PRISMA guidelines and using predefined inclusion and exclusion criteria, two reviewers independently and in parallel screened, assessed the studies' quality, and compiled data. Disagreements were resolved by consensus or consulting a third author. Results: This review included seven randomized control trials. Four articles demonstrated a significant increase in SIRT-1 with different RSV dosages and interventions time. The secondary outcomes showed improvements in insulin sensitivity, lipid profile, metabolic flexibility, total antioxidant capacity, energy expenditure changes, and reduction of ectopic accumulation of fat. Conclusion: Data from RCTs studies showed that RSV supplementation could stimulate SIRT-1 in humans, and therefore contribute to the treatment of excess weight and its comorbidities. However, more research is needed because it was not possible to confirm this effect truly. [PROSPERO registration number: CRD42020205571] [ABSTRACT FROM AUTHOR]

Purpose: Recent evidence has demonstrated that the gut microbiota plays a critical role in the treatment of obesity and other metabolic dysfunctions. Ginger (Zingiber officinale Roscoe), one of the most commonly used spices and dietary supplements, has been shown to exert beneficial effects against obesity and related disorders. However, to date, the mechanisms linking these effects to the gut microbiota remain unclear. This study aims to investigate the relationship between the gut microbiota and the metabolic adaptations resulting from ginger supplementation in mice. Methods: Four groups of mice were fed a normal chow diet (NCD) or a high-fat diet (HFD) with or without ginger supplementation for 16 weeks. Lipid profiles, proinflammatory cytokines, glucose tolerance, microbiota composition and short-chain fatty acid (SCFA) concentrations were analyzed at the end of the experiment. In addition, microbiota-depleted mice were transplanted with the fecal microbiota of mice fed a HFD or mice fed a HFD along with ginger supplementation. Glucose tolerance and microbiota composition were assessed after a 8-week fecal microbiota transplantation (FMT). Results: We observed marked decreases in body weight, liver steatosis, and low-grade inflammation as well as amelioration of insulin resistance in the HFD-fed mice treated with ginger. Furthermore, ginger supplementation modulated the gut microbiota composition and increased species belonging to the Bifidobacterium genus and SCFA-producing bacteria (Alloprevotella and Allobaculum), along with increases in fecal SCFA concentrations. The FMT experiment showed anti-obesity and microbiota-modulating effects similar to those observed in the oral ginger-feeding experiment. Conclusions: This study suggests that modulation of the gut microbiota as a result of ginger supplementation has a therapeutic effect on obesity in mice. [ABSTRACT FROM AUTHOR]

Background: Polycystic ovary syndrome (PCOS) is a frequent medical condition characterized by both metabolic and reproductive disorders. Different pharmaceutical treatments have been proposed for PCOS. However, side effects of long-term treatments and their probable low efficacy have made complementary and alternative treatments a valuable option. Recent reports have indicated the increased use of complementary treatments. Herbal medicine, as part of complementary medicine, was find introduced in traditional Persian and Chinese medicine. Medicinal herbs have used for a long time in the treatment of gynecological and infertility problems of PCOS patients. In this study, we aimed to review herbal medicines used for PCOS worldwide. Methods: PubMed, Embase, Cochrane, and Scopus databases were searched for clinical trials and Randomized Controlled Trials based on related keywords. Data were collected from 1990 to 2019. Results: According to a multitude of studies, a wide spectrum of herbs can be used to improve various aspects of PCOS. Herbs such as Cinnamomum verum, Trigonella foenum-graecum L., and Vitex agnus-castus can impact on menstrual and ovulatory dysfunctions, obesity, insulin resistance, lipid-metabolism dysfunction, and androgen excess-related conditions. Conclusion: Some plants as natural remedies may have beneficial effects on improving different aspects of PCOS; but further studies are needed to investigate their mechanisms and safety. [ABSTRACT FROM AUTHOR]

Purpose: In metabolic syndrome, the composition of gut microbiota has been disrupted, and is associated with left ventricular (LV) dysfunction. Several types of prebiotics, probiotics, and synbiotics have been shown to exert cardioprotection by restoring gut microbiota from dysbiosis and reducing systemic inflammation. However, the effects of prebiotics such as xylooligosaccharides (XOS); probiotics such as Lactobacillus paracasei STII01 HP4, and synbiotics on metabolic and LV function in obese insulin-resistant rats have not been investigated. In this study, we hypothesized that prebiotics and probiotics improve metabolic parameters, heart rate variability (HRV), blood pressure (BP), and LV function by attenuating cardiac mitochondrial dysfunction, systemic inflammation, and oxidative stress, and that synbiotics provide greater efficacy than a single regimen in obese insulin resistance.Methods: Rats were fed with either normal diet or high-fat diet (HFD) for 12 weeks and then rats in each dietary group were randomly subdivided into four subgroups to receive either a vehicle, prebiotics, probiotics, or synbiotics for another 12 weeks. Metabolic parameters, BP, HRV, LV function, cardiac mitochondrial function, systemic inflammation, and oxidative stress were determined.Results: HFD-fed rats had obese insulin resistance with markedly increased systemic inflammatory marker [Serum LPS; ND; 0.6 ± 0.1 EU/ml vs. HFD; 5.7 ± 1.2 EU/ml (p < 0.05)], depressed HRV, and increased BP and LV dysfunction [%ejection fraction; ND; 93 ± 2% vs. HFD; 83 ± 2% (p < 0.05)]. Prebiotics, probiotics, and synbiotics attenuated insulin resistance by improving insulin sensitivity and lipid profiles. All interventions also improved HRV, BP, LV function [%ejection fraction; HFV; 81 ± 2% vs. HFPE; 93 ± 3%, HFPO; 92 ± 1%, HFC; 92 ± 2% (p < 0.05)] by attenuating mitochondrial dysfunction, oxidative stress, and systemic inflammation in obese insulin-resistant rats.Conclusion: Prebiotics, probiotics, and synbiotics shared similar efficacy in reducing insulin resistance and LV dysfunction in obese insulin-resistant rats. [ABSTRACT FROM AUTHOR]

Obesity and latent inflammation in adipose tissue significantly contribute to the development of insulin resistance (IR) and type 2 diabetes. Here we studied whether the antiinflammatory interleukin-4 (IL-4) can restore insulin sensitivity in cultured 3T3-L1 adipocytes. The activity of key components of the insulin signaling cascade was assessed by immunoblotting using phospho-specific antibodies to insulin receptor substrate IRS1 (Tyr612), Akt (Thr308 and Ser473), and AS160 (Ser318) protein that regulates translocation of the GLUT4 glucose transporter to the plasma membrane. IR was induced in mature adipocytes with albumin-conjugated palmitate. IR significantly reduced phosphorylation levels of all the above-mentioned proteins. Addition of IL-4 to the culturing medium during IR induction led to a dose-dependent stimulation of the insulin-promoted phosphorylation of IRS1, Akt, and AS160. At the optimal concentration of 50 ng/ml, IL-4 fully restored activation of the insulin cascade in IR cells, but it did not affect insulin signaling activation in the control cells. IL- 4 neither upregulated expression of key adipogenesis markers GLUT4 and PPARγ nor caused lipid accumulation in the adipocytes. These results demonstrate that IL-4 can restore insulin sensitivity in adipocytes via mechanisms not associated with induced adipogenesis or de novo formation of lipid depots. [ABSTRACT FROM AUTHOR]

Purpose: This study examined the feasibility of sprint interval exercise training (SIT) for men with non-alcoholic fatty liver disease (NAFLD) and its effects on intrahepatic triglyceride (IHTG), insulin sensitivity (hepatic and peripheral), visceral (VAT) and subcutaneous adipose tissue (ScAT).Methods: Nine men with NAFLD (age 41 ± 8 years; BMI 31.7 ± 3.1 kg m-2; IHTG 15.6 ± 8.3%) were assessed at: (1) baseline (2) after a control phase of no intervention (pre-training) and (3) after 6 weeks of SIT (4-6 maximal 30 s cycling intervals, three times per week). IHTG, VAT and ScAT were measured using magnetic resonance spectroscopy or imaging and insulin sensitivity was assessed via dual-step hyperinsulinaemic-euglycaemic clamp with [6,6-D2] glucose tracer.Results: Participants adhered to SIT, completing ≥ 96.7% of prescribed intervals. SIT increased peak oxygen uptake [[Formula: see text] peak: + 13.6% (95% CI 8.8-18.2%)] and elicited a relative reduction in IHTG [- 12.4% (- 31.6 to 6.7%)] and VAT [- 16.9% (- 24.4 to - 9.4%); n = 8], with no change in body weight or ScAT. Peripheral insulin sensitivity increased throughout the study (n = 8; significant main effect of phase) but changes from pre- to post-training were highly variable (range - 18.5 to + 58.7%) and not significant (P = 0.09), despite a moderate effect size (g* = 0.63). Hepatic insulin sensitivity was not influenced by SIT.Conclusions: SIT is feasible for men with NAFLD in a controlled laboratory setting and is able to reduce IHTG and VAT in the absence of weight loss. [ABSTRACT FROM AUTHOR]

Purpose: Myricetin, a dietary flavonoid, is effective in the treatment of obesity and insulin resistance by increasing glucose transport and lipogenesis in adipocyte and diminishing systemic inflammation in obesity. However, it has not been revealed yet whether myricetin is associated with brown adipose tissue (BAT) activation that tightly mediates systemic energy metabolism. Therefore, this study assessed whether myricetin activated brown adipose tissue in db/db mouse.Methods: Myricetin (400 mg/kg) in distilled water was fed daily by oral gavage to leptin receptor-deficient db/db male mice at 4 weeks of age for 14 weeks. Body weight change, glucose intolerance test, blood lipid profile and BAT activation using PET-CT were assessed.Results: After myricetin treatment for 14 weeks, systemic insulin resistance and hepatic steatosis were significantly improved in db/db mice with body weight reduction and myricetin led to decreased adipocity, improved plasma lipid profiles and increased energy expenditure. Myricetin activated BAT by upregulating thermogenic protein expression and activating mitochondrial biogenesis, eventually increasing heat dissipation in skin after cold exposure. In iWAT, myricetin induced beige formation, increased thermogenic protein expression and activated mitochondrial biogenesis. Consistently, thermogenic gene expression was upregulated when myricetin was introduced in C3H10T1/2 cells during brown adipocytes differentiation. Moreover, the expression level of adiponectin was significantly increased in C3H10T1/2 cells, adipose tissues and plasma after myricetin treatment.Conclusions: These results highlight that myricetin prevents obesity and systemic insulin resistance by activating BAT and increasing adiponectin expression in BAT. [ABSTRACT FROM AUTHOR]

Summary: This study investigated the association between lipid profiles and insulin resistance and bone mineral content (BMC) in Korean adolescents and found that BMC was inversely associated with triglyceride (TG) and homeostasis model assessment of insulin resistance (HOMA-IR). This association did not differ according to obesity status in either boys or girls. Introduction: To prevent future osteoporosis, it is important to identify factors that affect bone health in adolescents as well as adults. This study aimed to examine the association between lipid profiles and insulin resistance and BMC in Korean adolescents. Methods: Data from 706 boys and 621 girls, who participated in the Korea National Health and Nutrition Examination Survey from 2008 to 2011, were analyzed. Lipid profiles were measured, and HOMA-IR was calculated to assess insulin resistance. BMC was measured for the total femur, femur neck, and lumbar spine by using whole-body dual-energy X-ray absorptiometry (DXA). Results: TG level and HOMA-IR were negatively correlated with BMC at all three sites in boys. In girls, TG level showed a negative correlation with BMC at the femur neck and lumbar spine, and HOMA-IR was negatively associated with BMC at the femur neck only. These inverse associations did not differ according to obesity status in either sex. Adjusted means of BMC at the three sites in boys tended to decrease in the higher tertile groups of TG and HOMA-IR, and the adjusted means of BMC for the total femur in girls tended to decrease in the higher tertile groups of TG and HOMA-IR. Conclusions: BMC was inversely associated with TG and HOMA-IR in Korean adolescents, and this association was more pronounced in boys. This association did not differ according to obesity status in either sex. [ABSTRACT FROM AUTHOR]

Unlabelled: The aim of this study was to analyze changes in adipose tissue (AT) distribution, intrahepatic lipids (IHL), and insulin resistance (IR) among a group of obese adolescents undergoing a 7-months low-level lifestyle intervention. Thirty-nine obese Caucasian adolescents (mean age 13.9 years, body mass index standard deviation score (BMI-SDSLMS) 2.14) were included. AT and IHL were determined by T1-weighted magnetic resonance (MR) imaging and single-voxel MR spectroscopy; IR was estimated using the homeostatic model assessment (HOMA-IR). The lifestyle intervention led to a reduction of both BMI-SDSLMS (boys 2.27 to 2.17; girls 2.00 to 1.82) and HOMA-IR (boys 6.1 to 4.4 (p = 0.008); girls 6.2 to 4.7 (p = 0.030)). IHL dropped in both genders (boys 7.5 to 4.3 %; girls 4.6 to 3.4 %) positively correlating with HOMA-IR (boys r = 0.52; girls r = 0.68), while in contrast visceral AT did not change significantly.Conclusions: Although the lifestyle intervention only slightly reduced BMI-SDSLMS, insulin sensitivity improved in both genders and came along with a marked reduction of IHL. This suggests that IHL might play the dominant role regarding insulin resistance in the youth, especially if compared to other AT compartments such as visceral AT.What Is Known: • MR imaging/spectroscopy can be used to evaluate body fat distribution and intrahepatic lipids in the youth. • The strength of associations between body fat compartments and insulin resistance is under scientific debate.What Is New: • The study emphasizes that even a low-level lifestyle intervention has a beneficial effect. • The study suggests that intrahepatic lipids are an important factor in the development of insulin resistance. [ABSTRACT FROM AUTHOR]

Metabolic syndrome (MetS) is a cluster of metabolic traits associated with an increased risk of cardiovascular disease and type 2 diabetes mellitus. Central obesity and insulin resistance are thought to play key roles in the pathogenesis of the MetS. The MetS has a significant genetic component, and therefore linkage analysis, candidate gene approach, and genome-wide association (GWA) studies have been applied in the search of gene variants for the MetS. A few variants have been identified, located mostly in or near genes regulating lipid metabolism. GWA studies for the individual components of the MetS have reported several loci having pleiotropic effects on multiple MetS-related traits. Genetic studies have provided so far only limited evidence for a common genetic background of the MetS. Epigenetic factors (DNA methylation and histone modification) are likely to play important roles in the pathogenesis of the MetS, and they might mediate the effects of environmental exposures on the risk of the MetS. Further research is needed to clarify the role of genetic variation and epigenetic mechanisms in the development of the MetS. [ABSTRACT FROM AUTHOR]

Metabolic syndrome (MetS) is a clinical condition that includes multiple cardiovascular disease risk factors, including obesity, high blood pressure or hypertension, dyslipidemia, and abnormal glucose metabolism. The core metabolic abnormality in MetS is insulin resistance, or impaired insulin-mediated glucose regulation that results in elevated plasma insulin concentration. MetS greatly increases the risk for diabetes, atherosclerosis, and adverse metabolic and cardiovascular outcomes. The syndrome is present in over 25 % of adults in the U.S., with higher rates among racial/ethnic minority groups. Although commonly associated with adult diseases and aging, MetS has also been described in children and adolescents, but at a much lower prevalence of approximately 4-5 %. Because obesity is a key component of the syndrome, the growing childhood epidemic has raised awareness of MetS in children. The rate of MetS among obese children and adolescents is approximately 30 %, with similar racial/ethnic disparity among minority groups as among adults. [ABSTRACT FROM AUTHOR]

Purpose: We showed that early weaned rats developed obesity, hyperleptinemia, leptin and insulin resistance at adulthood. Here, we studied the potential beneficial effects of Ilex paraguariensis aqueous solution upon body composition, glycemia, lipid and hormonal profiles, leptin signaling and NPY content. Methods: To induce early weaning, lactating rats' teats were blocked with a bandage to interrupt lactation during the last 3 days (EW group), while control offspring had free access to milk throughout lactation (C group). In postnatal day (PN) 150, EW offspring were subdivided into: EW and EW+ mate groups treated, respectively, with water or yerba mate aqueous solution (1 g/kg BW/day, gavage) during 30 days. C offspring received water for gavage. In PN180, offspring were killed. Results: EW+ mate group presented lower body weight (−10 %), adipose mass (retroperitoneal:−40 % and epididymal:−44 %), total body fat (−43 %), subcutaneous fat (−46 %), visceral adipocyte area (−21 %), triglyceridemia (−31 %) and hypothalamic NPY content (−37 %) compared to EW group. However, hyperglycemia and lower HDL-c levels observed in EW group were not reverted with mate treatment. Although the hyperleptinemia, lower hypothalamic JAK2 and pSTAT3 content of EW group were not corrected by mate treatment, the hyperphagia and higher hypothalamic SOCS-3 content were normalized in EW+ mate group, indicating that the central leptin resistance could be restored. Conclusion: Thus, the therapy with yerba mate solution was capable to reverse abdominal obesity, leptin resistance and hypertriglyceridemia, suggesting an important role of this bioactive component in the management of obesity in this programming model. [ABSTRACT FROM AUTHOR]

Diabetes mellitus is a chronic disease with a higher risk of associated infections. HIV infection severely affects diabetic patients and acts as a significant health concern. Highly active antiretroviral therapy (HAART) has changed HIV from an acute infection to a chronic infection with associated significant metabolic abnormalities such as insulin resistance, impaired glucose tolerance, metabolic syndrome, diabetes, dyslipidemia, obesity, and lipodystrophy. These metabolic disturbances add complexity to the standards of care in HIV infection and further increase the risk for cardiovascular disease and renal complications. The co-association of diabetes and HIV needs to be managed appropriately to prevent mortality and morbidity and improve patient outcome. The current understanding of diabetes and other metabolic abnormalities along with management strategies in HIV infected patients are summarized in this article. The review also focuses on recent challenges in the diagnosis and management of co-existent diabetes and HIV infection. [ABSTRACT FROM AUTHOR]

Lipids in skeletal muscle play a fundamental role both in normal muscle metabolism and in disease states. Skeletal muscle lipid accumulation is associated with several chronic metabolic disorders, including obesity, insulin resistance, and type 2 diabetes. However, it is poorly understood whether the lipid composition of skeletal muscle changes by contraction, due to the complexity of lipid molecular species. In this study, we used matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS) to investigate changes in skeletal muscle lipid composition induced by contraction. We successfully observed the reduction of diacylglycerol and triacylglycerol, which are generally associated with muscle contraction. Interestingly, we found the accumulation of some saturated and mono-unsaturated fatty acids and poly-unsaturated fatty acids containing phosphatidylcholine in contracted muscles. Moreover, the distributions of several types of lipid were changed by contraction. Our results show that changes in the lipid amount, lipid composition, and energy metabolic activity can be evaluated in each local spot of cells and tissues at the same time using MALDI-IMS. In conclusion, MALDI-IMS is a powerful tool for studying lipid changes associated with contractions. [ABSTRACT FROM AUTHOR]

Inadequate minerals intake, as well as disruption of some metabolic processes in which microelements are cofactors, are suggested to lead to the development of hypertension. The role of minerals in the pathogenesis of hypertension still remains to be explained. In the present study, we sought to determine associations between serum and hair mineral concentrations and serum lipids and glucose levels. Forty obese hypertensive subjects with insulin resistance and 40 healthy volunteers were recruited in the study. Blood pressure, BMI, and insulin resistance were recorded in all subjects. Levels of lipids, glucose, sodium and potassium, iron, copper, zinc, magnesium, and calcium were assessed in serum. Iron, copper, zinc, magnesium, and calcium were assessed in hair. Dietary intake of the analyzed minerals was estimated. We found distinctly higher concentrations of serum iron and serum and hair calcium as well as markedly lower levels of hair zinc in the hypertensive subjects. The study group manifested also significantly lower daily intake of calcium, magnesium, and iron. We observed a relationship between the concentrations of iron, zinc, and copper in serum and hair and high and low range of cholesterol, triglycerides, and glucose serum levels in the studied patients. Moreover, this study demonstrated significant correlation between serum and hair concentrations of selected minerals and their dietary intake and levels of serum lipids and glucose and blood pressure in the study and the control groups. The obtained results seem to indicate the association between lipid and glucose metabolism and iron, copper, zinc, and calcium concentrations in blood and hair of hypertensive and obese patients with insulin resistance. [ABSTRACT FROM AUTHOR]

Despite the well-established observation that substitution of saturated fats for carbohydrates or unsaturated fats increases low-density lipoprotein (LDL) cholesterol in humans and animal models, the relationship of saturated fat intake to risk for atherosclerotic cardiovascular disease in humans remains controversial. A critical question is what macronutrient should be used to replace saturated fat. Substituting polyunsaturated fat for saturated fat reduces LDL cholesterol and the total cholesterol to high-density lipoprotein cholesterol ratio. However, replacement of saturated fat by carbohydrates, particularly refined carbohydrates and added sugars, increases levels of triglyceride and small LDL particles and reduces high-density lipoprotein cholesterol, effects that are of particular concern in the context of the increased prevalence of obesity and insulin resistance. Epidemiologic studies and randomized clinical trials have provided consistent evidence that replacing saturated fat with polyunsaturated fat, but not carbohydrates, is beneficial for coronary heart disease. Therefore, dietary recommendations should emphasize substitution of polyunsaturated fat and minimally processed grains for saturated fat. [ABSTRACT FROM AUTHOR]

There is renewed interest in high-density lipoproteins (HDLs) due to recent findings linking atherosclerosis to the formation of dysfunctional HDL. This article focuses on the universe of HDL lipids and their potential protective or proinflammatory roles in vascular disease and insulin resistance. HDL carries a wide array of lipids including sterols, triglycerides, fat-soluble vitamins, and a large number of phospholipids, including phosphatidylcholine, sphingomyelin, and ceramide with many biological functions. Ceramide has been implicated in the pathogenesis of insulin resistance and has many proinflammatory properties. In contrast, sphingosine-1-phosphate, which is transported mainly in HDL, has anti-inflammatory properties that may be atheroprotective and may account for some of the beneficial effects of HDL. However, the complexity of the HDL lipidome is only beginning to reveal itself. The emergence of new analytical technologies should rapidly increase our understanding of the function of HDL lipids and their role in disease states. [ABSTRACT FROM AUTHOR]

During the last decades, the prevalence of obesity, diabetes mellitus and metabolic syndrome (MetS) has dramatically risen in developed countries. A further increase in MetS and diabetes can be anticipated because of projections of a greater prevalence of obesity in the future. Albeit the cardiovascular (CV) risk in patients with MetS has been considered high, a large proportion of these patients present with normal low-density lipoprotein-cholesterol (LDL-C) levels. Conversely, these patients often display high levels of apolipoprotein B-100 (apoB), triglycerides (TG) and non-high-density lipoprotein-cholesterol (non- HDL-C). Among routine lipoprotein assessment, the use of non-HDL-C has shown several advantages over LDL-C, particularly in the presence of hypertriglyceridaemia. Non-HDL-C is a combined measurement of LDL-C, lipoprotein (a), small dense LDL-C (sd-LDL-C), chilomicron remnants, and intermediate-density lipoproteins. Several studies have shown that non-HDL-C is a strong predictor of subclinical atherosclerosis and CV events as well as a reasonable surrogate of apoB measurement. Moreover, current evidence is supporting that non-HDL-C accurately predicts major CV events even in patients with normal TG values. However, current recommendations suggest non-HDL-C only when TG exceeds 200mg/dL, recommending the use of LDL-C as the primary target of therapy in all the other conditions. These definitions contrast with the finding of normal LDL-C in obesity, diabetes and MetS, all considered high-risk conditions. Therefore, a redefinition of LDL-C as a predictor of CV events is needed also in the view of an increased prevalence of insulin resistance, abdominal obesity and diabetes. [ABSTRACT FROM AUTHOR]

Objective:To determine whether increased expression of macrophage markers and of inflammatory markers in subcutaneous adipose tissue is associated with liver fat in human obesity. We also determined whether expression of TNF (gene encoding TNF-α), HSD11B1 (gene encoding 11β-HSD-1) and RETN (gene encoding resistin) in cultured monocyte-derived macrophages differs between obese/overweight and non-obese subjects.Design:Cross-sectional comparison of obese/overweight and non-obese subjects with respect to adipose tissue gene expression, gene expression in monocyte-derived macrophages, liver fat content and in vivo insulin sensitivity.Subjects:Adipose tissue gene expression, gene expression in monocyte-derived macrophages, liver fat content and in vivo insulin sensitivity: 10 healthy non-obese (24.2±1.0 kg/m2) and 10 healthy obese/overweight (33.1±1.7 kg/m2) women. Gene expression in monocyte-derived macrophages: seven healthy non-obese (22.1±0.7 kg/m2) and seven healthy obese/overweight (36.9±2.2 kg/m2) women.Measurements:Adipose tissue biopsies and blood samples for isolation of peripheral mononuclear cells were taken after an overnight fast. Liver fat content was measured using magnetic resonance proton spectroscopy. Whole body insulin sensitivity was measured using the hyperinsulinemic euglycemic clamp technique. Expression levels of TNF, HSD11B1, RETN and the macrophage markers CD68 and ITGAM were determined by real-time PCR.Results:In adipose tissue, expression of HSD11B1, ITGAM and CD68 was significantly increased in the obese/overweight as compared to the non-obese group. Expression of all these genes was closely positively correlated with liver fat content and inversely correlated with whole body insulin sensitivity. The associations between expression of CD68, ITGAM and HSD11B1 and liver fat were independent of obesity. There were no differences in TNF, HSD11B1, RETN or CD68 gene expression basally or after stimulation with lipopolysaccharide in monocyte-derived macrophages between obese/overweight and non-obese subjects.Conclusion:Accumulation of fat in the liver is associated with increased adipose tissue inflammation independent of obesity.International Journal of Obesity (2007) 31, 1617–1625. doi:10.1038/sj.ijo.0803635; published online 24 April 2007 [ABSTRACT FROM AUTHOR]

Stearoyl CoA desaturase 1 (SCD1) is implicated in mediating obesity and insulin resistance. Paradoxically, SCD1 converts saturated fatty acids, the lipid species implicated in mediating insulin resistance, to monounsaturated fatty acids. The aim of the present study was to assess the molecular mechanisms that implicate SCD1 in the aetiology of fatty acid-induced insulin resistance. SCD1 protein was transiently decreased or increased in rat L6 skeletal muscle myotubes using SCD1 short interfering RNA (siRNA) or liposome-mediated transfection of pcDNA3.1/Hygro-mSCD1, respectively. Reducing SCD1 protein resulted in marked esterification of exogenous fatty acids into diacylglycerol (DAG) and ceramide. Insulin-stimulated Akt activity and phosphorylation and 2-deoxyglucose uptake were reduced with SCD1 siRNA. Exposure of L6 myotubes to palmitate abolished insulin-stimulated glucose uptake in both control and SCD1 siRNA myotubes. Overexpression of SCD1 resulted in triacylglycerol esterification but attenuated ceramide and DAG accumulation and protected myotubes from fatty acid-induced insulin resistance. SCD1 protects from cellular toxicity in L6 myotubes by preventing excessive accumulation of bioactive lipid metabolites. [ABSTRACT FROM AUTHOR]

The nuclear receptors, including nuclear receptor subfamily 1, group H, member 3 (NR1HR, also known as liver X receptor [LXR]), are sensors of cholesterol metabolism and lipid biosynthesis that have recently been proposed as insulin sensitisers. TNFα has been described as a link between obesity and the development of insulin resistance, an important contributor to the pathogenesis of type 2 diabetes. Therefore, we decided to investigate the ability of NR1HR agonists to ameliorate TNFα-induced insulin resistance in brown adipocytes. Primary brown adipocytes from rat fetuses, and from wild-type neonate mice and neonate mice deficient in the gene encoding protein tyrosine phosphatase-1B ( Ptpn1, also known as Ptp1b) were cultured in the absence or presence of TNFα and different nuclear receptor agonists. Among them, the unrelated NR1HR ligands T0901317, GW3965 and (22 R)-hydroxycholesterol were tested. After insulin stimulation, glucose uptake and solute carrier family 2 (facilitated glucose transporter), member 4 (SLC2A4, formerly known as GLUT4) translocation were measured. Next the insulin signalling cascade was determined by submitting cells to lysis, immunoprecipitation and immunoblotting. NR1HR agonists ameliorate TNFα-induced insulin resistance restoring completely insulin-stimulated glucose uptake and SLC2A4 translocation to plasma membrane. This effect is parallel to the recovery of the insulin cascade insulin receptor/IRS-2/phosphatidylinositol 3-kinase/protein kinase B, and could be due to the fact that T0901317 prevents the increase of PTPN1 production and phosphatase activity produced by TNFα. In this regard, Ptpn1-deficient brown adipocytes showed protection against insulin resistance by TNFα. Moreover, we observed that T0901317 produced in itself a significant increase over basal glucose uptake consistent with an increase of SLC2A4 protein content in plasma membrane, attributable to the activation of protein kinase ζ and/or the increase of Slc2a4 expression. Nuclear receptors NR1HR are interesting potential targets for drug treatment of insulin resistance. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate the effects of a submaximal aerobic exercise bout on adiponectin and resistin levels as well as insulin sensitivity, until 48 h post-exercise in healthy overweight males. Nine subjects performed an exercise bout at an intensity corresponding to approximately 65% of their maximal oxygen consumption for 45 min. Adiponectin, resistin, cortisol, insulin, glucose and insulin sensitivity were measured prior to exercise, immediately after exercise as well as 24 and 48 h after exercise. Data were analyzed using repeated measures ANOVA while Pearson's correlations were performed to identify possible relationship among the assessed variables. There were no significant differences for adiponectin (microg ml(-1)) [pre, 3.61(0.73); post, 3.15(0.43); 24 h, 3.15(0.81); 48 h, 3.37(0.76)] or resistin (ng ml(-1)) [pre, 0.19(0.03); post, 0.13(0.03); 24 h, 0.23(0.04); 48 h, 0.23(0.03)] across time. Insulin sensitivity increased and insulin concentration decreased significantly only immediately after exercise. Furthermore, no significant correlations were observed among the variables assessed except for the expected between insulin level and insulin sensitivity. These results indicate that a submaximal aerobic workout does not result in significant changes in adiponectin and resistin up to 48 h post-exercise. Furthermore, it appears that adiponectin or resistin is not associated with insulin sensitivity. [ABSTRACT FROM AUTHOR]

Objective:To compare the value of body fat mass (%FM) to indirect measures of general (body mass index (BMI)) and central adiposity (waist circumference (WC); waist-to-height ratio (WC/ht)) for the prediction of overweight- and obesity-related metabolic risk in a study population with a high prevalence of metabolic syndrome (MSX).Methods:BMI, WC, WC/ht, body composition (by air-displacement plethysmography) and metabolic risk factors: triglycerides, cholesterol, HDL-cholesterol (HDL-C), uric acid, systolic blood pressure (BPsys), insulin resistance by homeostasis model assessment (HOMA-IR) and C-reactive protein (CRP) were measured in 335 adults (191 women, 144 men; mean age 53 ±13.9 years, prevalence of MSX 30%).Results:When compared with BMI and WC, %FM showed weaker associations with metabolic risk factors, except for CRP and BPsys in men. In women, HDL-C and HOMA-IR showed the closest correlations with BMI. For all other risk factors, WC or WC/ht were the best predictors in both sexes. Differences in the strength of correlations between an obesity index and different risk factors exceeded the differences observed between all obesity indices within one risk factor. In stepwise multiple regression analyses, WC/ht was the main predictor of metabolic risk in both sexes combined. However, analysis of the area under receiver operating characteristic curves for prediction of the prevalence of 2 component traits of the MSX revealed a similar accuracy of all obesity indices.Conclusions:At the population level, measurement of body FM has no advantage over BMI and WC in the prediction of obesity-related metabolic risk. Although measures of central adiposity (WC, WC/ht) tended to show closer associations with risk factors than measures of general adiposity, the differences were small and depended on the type of risk factor and sex, suggesting an equivalent value of methods.International Journal of Obesity (2006) 30, 475–483. doi:10.1038/sj.ijo.0803144; published online 1 November 2005 [ABSTRACT FROM AUTHOR]

Obese subjects need additional energy to move larger bodies and a greater amount of O2 to accomplish an equal external work-load than lean subjects. Moreover, obesity is characterized by a marked insulin resistance, which may modify metabolic responses to physical exercise. We measured the respiratory and metabolic responses to a progressive ergometric test in a group of 10 men obese and in 10 lean controls. Muscle biopsies of the left quadriceps were performed to study correlations between metabolic responses and muscle morphology. Oxygen consumption, carbon dioxide production and the respiratory exchange ratio (RER) were assessed, as were plasma concentrations of K+ and catecholamines in the basal state (rest) and during the last 30 s of each work load at exercise. Lactic acid was also measured. Obese subjects achieved a lower maximal power output (129 vs. 140 W) and a significantly lower anaerobic threshold (82 vs. 114 W, p<0.05). RER was significantly lower in the obese group, and catecholamines rose earlier and with a lower peak in correspondence of maximal power outputs. K+ and lactic acid levels increased in both groups, although significantly less in obese subjects. The main feature of muscle specimens from obese subjects was hypertrophy of the fibers, present in 9 of 10 cases, and increased amounts of neutral lipids (Oil Red O staining), present in 7 of 10 individuals. Low RER in obese subjects indicated a condition of insulin resistance, which persisted during physical activity. We conclude that fats are the fuel preferred by obese individuals during strenuous exercise. [ABSTRACT FROM AUTHOR]

The potential lipotoxic effect of intramyocellular triglyceride (IMTG) accumulation has been suggested to be a major component in the development of insulin resistance. Increased levels of IMTGs correlate with insulin resistance in both obese and diabetic patients, but this relationship does not exist in endurance trained (ETr) subjects. This may be, in part, related to differences in the gene expression and activities of key enzymes involved in fatty acid transport and oxidation as well as in the perodixation status of the IMTGs in obese/diabetic patients as compared with ETr subjects. Disruptions in fat and lipid homeostasis in skeletal muscle have been shown to activate protein kinase C (PKC), which acts on several downstream signalling pathways, including the insulin and the I?B kinase (IKK)/NF?B signalling pathways. Additionally, an increased peroxidation of IMTGs may reduce insulin sensitivity by increasing TNFa, which is known to increase the expression of suppressor of cytokine signalling proteins (SOCS). A common characteristic observed when activating both PKC and TNFa/SOCS3 is the inhibition of tyrosine phosphorylation of IRS-1 and subsequently an inhibition of its activation of downstream signalling molecules. These may be important players in the development of insulin resistance and understanding their activation and expression in both obese and ETr humans should assist in understanding how and why IMTGs become lipotoxic.International Journal of Obesity (2004) 28, S66-S71. doi:10.1038/sj.ijo.0802859 [ABSTRACT FROM AUTHOR]

OBJECTIVES:: To estimate the prevalence of insulin resistance syndrome (IRS) in a representative sample of youth. To test for the independent contribution of insulin resistance (IR) and adiposity to clustering of metabolic risk factors. To identify the underlying components of IRS. To examine the relationship between adiposity and fasting plasma levels of free fatty acids (FFA). METHODS:: In 1999, we conducted a school-based survey of a representative sample of youth aged 9, 13 and 16?y in Quebec, Canada. Age-specific questionnaire data, standardized clinical measurements and a fasting blood sample were available for 2244 subjects. Fasting insulin and HOMA were used as surrogate measures of IR. RESULTS:: In all age-sex groups, adiposity indices, blood pressure (BP), plasma glucose and triglycerides (TG) increased significantly with increasing insulin quartiles while HDL cholesterol (HDL-C) decreased. The overall prevalence of IRS defined as hyperinsulinaemia combined with two or more risk factors including overweight, high systolic BP, impaired fasting glucose, high TG and low HDL-C, was 11.5% (95% CI: 10.2-12.9). There were no significant differences in the prevalence of IRS across ages or between sexes. The independent contribution of adiposity to clustering of risk factors was stronger than that of fasting insulin (or HOMA-IR). Factor analysis revealed three factors (BMI/insulin/lipids, BMI/insulin/glucose and diastolic/systolic BP) consistent across ages suggesting that more than one pathophysiologic process underlies IRS. Although elevation of FFA might be in the causal pathway linking obesity to IR, we did not detect any consistent association between measures of fatness and fasting plasma FFA. CONCLUSION:: IRS is highly prevalent in youth, even among children as young as age 9?y. Factor analysis identifies three physiologic domains within IRS with a unifying role for markers of IR and adiposity.International Journal of Obesity (2004) 28, 833-841. doi:10.1038/sj.ijo.0802694 Published online 1 June 2004 [ABSTRACT FROM AUTHOR]

OBJECTIVE: The aim of this study was to examine changes in lipid profile and markers of insulin resistance with increasing body mass index (BMI) in the range 34-77 kg/m². In addition we compare the lipid profiles of severely obese patients with those of the Australian community. SUBJECTS AND METHODS: A total of 572 patients (85% F, 15% M) were assessed prior to gastric restrictive surgery. Conventional lipid profiles and markers of insulin resistance were measured. Lipids were compared with the Australian National Heart Foundation 1989 study (control group). RESULT: There was no difference in mean total cholesterol levels between the obese group (5.52 mmol/l) and the control group (5.47 mmol/1). The mean total cholesterol levels in the obese group fell with increasing BMI (r=-0.13, P<0.01). Obese subjects had elevated fasting triglyceride levels 1.96 mmol/l (control group, 1.12 mmol/l, P < 0.001), but levels did not change with increasing BMI (r=0.0, NS). HDL-C levels were lower, 1.21 mmol/l (control group 1.44 mmol/l, P < 0.001), and decreased with increasing BMI (r=-0.20, P<0.01). LDL-C levels were lower in obese men (3.65 mmol/l vs control group 4.17 mmol/l, P<0.01) but not women and levels fell with increasing BMI (r=-0.15, P<0.05). For the obese group, markers of insulin resistance (fasting plasma glucose, HbA1c, fasting plasma insulin and C-peptide) all rose significantly with increasing BMI. CONCLUSION: Raised total cholesterol is not a co-morbidity of severe obesity. There is a disparity between the conventional lipid measures and insulin resistance measures of the metabolic syndrome with increasing BMI. Conventional lipid measures may be poor indicators of dyslipidaemic risk in the severely obese. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The aim of this study was to examine changes in lipid profile and markers of insulin resistance with increasing body mass index (BMI) in the range 34-77 kg/m². In addition we compare the lipid profiles of severely obese patients with those of the Australian community. SUBJECTS AND METHODS: A total of 572 patients (85% F, 15% M) were assessed prior to gastric restrictive surgery. Conventional lipid profiles and markers of insulin resistance were measured. Lipids were compared with the Australian National Heart Foundation 1989 study (control group). RESULT: There was no difference in mean total cholesterol levels between the obese group (5.52 mmol/l) and the control group (5.47 mmol/1). The mean total cholesterol levels in the obese group fell with increasing BMI (r=-0.13, P<0.01). Obese subjects had elevated fasting triglyceride levels 1.96 mmol/l (control group, 1.12 mmol/l, P < 0.001), but levels did not change with increasing BMI (r=0.0, NS). HDL-C levels were lower, 1.21 mmol/l (control group 1.44 mmol/l, P < 0.001), and decreased with increasing BMI (r=-0.20, P<0.01). LDL-C levels were lower in obese men (3.65 mmol/l vs control group 4.17 mmol/l, P<0.01) but not women and levels fell with increasing BMI (r=-0.15, P<0.05). For the obese group, markers of insulin resistance (fasting plasma glucose, HbA1c, fasting plasma insulin and C-peptide) all rose significantly with increasing BMI. CONCLUSION: Raised total cholesterol is not a co-morbidity of severe obesity. There is a disparity between the conventional lipid measures and insulin resistance measures of the metabolic syndrome with increasing BMI. Conventional lipid measures may be poor indicators of dyslipidaemic risk in the severely obese. [ABSTRACT FROM AUTHOR]

Aims/hypothesis. Information on the association of hyperinsulinaemia with coronary heart disease (CHD) in patients with Type II (non-insulin-dependent) diabetes is limited and controversial. Therefore, we carried out a prospective study to examine the predictive value of fasting plasma insulin and “hyperinsulinaemia cluster” with regard to the risk of CHD mortality.¶Methods. At baseline risk factors for CHD were determined in 902 patients aged 45 to 64 years with Type II diabetes not treated by insulin (499 men and 403 women). These patients were followed up to 7 years for CHD mortality.¶Results. Coronary heart disease mortality (16.2 % in men, 9.2 % in women) increased significantly in men with increasing plasma insulin tertiles (p = 0.006) and in both sexes combined (p = 0.010) but not in women (p = 0.090). The predictive value of hyperinsulinaemia with regard to death from CHD was independent of conventional cardiovascular risk factors but not of risk factors clustering with hyperinsulinaemia. By applying factor analysis and principal component analysis we showed that “hyperinsulinaemia cluster” (a factor having high positive loadings for body mass index, triglycerides and insulin; and a high negative loading for high-density lipoprotein cholesterol) was predictive of death from CHD in patients with Type II diabetes (hazard ratio with 95 % confidence intervals 1.43 (1.18, 1.73), p < 0.001).¶Conclusion/interpretation. Our results support the notion that cardiovascular risk factors clustering with endogenous hyperinsulinaemia increase the risk of death from CHD in patients with Type II diabetes not treated with insulin. [Diabetologia (2000) 43: 148–155] [ABSTRACT FROM AUTHOR]

Background: The role of resistant starch (RS) in glucose, insulin, insulin resistance or sensitivity, and lipid parameters have been reported in several studies and remained controversial. A pooled analysis which assessed these parameters has not been performed. Thus, we conducted a meta-analysis to sum up existing evidence about the issue. Methods: We searched in MEDLINE and PUBMED for studies that were published before November 2018. Meta-analysis of diabetics and nondiabetics trials were performed by use of a random-effects model. Results: A total of 13 case–control studies that included 428 subjects with body mass index ≥25 were identified. RS supplementation reduced fasting insulin in overall and stratified (diabetics and nondiabetics trials) analysis (SMD = –0.72; 95% CI: –1.13 to –0.31; SMD = –1.26; 95% CI: –1.66 to –0.86 and SMD = –0.64; 95% CI: –1.10 to –0.18, respectively), and reduced fasting glucose in overall and stratified analysis for diabetic trials (SMD = –0.26; 95% CI: –0.5 to –0.02 and SMD = –0.28; 95% CI: –0.54 to –0.01, respectively). RS supplementation increased HOMA-S% (SMD = 1.19; 95% CI: 0.59–1.78) and reduced HOMA-B (SMD =–1.2; 95% CI: –1.64 to –0.77), LDL-c concentration (SMD =–0.35; 95% CI: –0.61 to −0.09), and HbA1c (SMD = –0.43; 95% CI: –0.74 to –0.13) in overall analysis. Conclusions: This meta-analysis has provided evidence that RS supplementation can improve fasting glucose, fasting insulin, insulin resistance and sensitivity, especially for diabetic with overweight or obesity. However, owing to potential sophistication, individual difference and composition of intestinal microbiota, this result should be carefully taken into account. [ABSTRACT FROM AUTHOR]

The article discusses the mechanisms of actions for JUN N-terminal kinase 1 (JNK1) in upgrading obesity-induced insulin resistance. It highlights the potential of JNK1 expression in non-haematopoietic cells in promoting insulin resistance through the regulation of lipid accumulation. Apart from this, the study showed that JNK1 expression in haematopoietic cells promotes insulin resistance through obesity-associated inflammation and the production of cytokines that stimulate insulin resistance.