Higher Fasting Insulin Research Articles

Risk for obstructive sleep apnea in obese, nondiabetic adults varies with insulin resistance status

Obstructive sleep apnea (OSA) is an increasingly common sleep disorder, especially among obese adults. Early identification of adults at risk for OSA would be of substantial benefit; however, the magnitude of the obesity epidemic requires that screening be performed judiciously. The study's aim was to utilize questionnaires that assess OSA risk and symptoms to test the hypothesis that the most insulin-resistant subset of obese individuals is at highest risk for OSA. Nondiabetic, overweight to obese volunteers underwent direct quantification of insulin sensitivity by measuring steady-state plasma glucose concentrations during the insulin suppression test. Insulin-sensitive and insulin-resistant individuals were administered the Berlin and STOP questionnaires to determine OSA risk status, and Epworth Sleepiness Scale (ESS) to evaluate daytime sleepiness. Fasting insulin and lipid/lipoprotein measurements were performed. Insulin-mediated glucose disposal differed threefold (p < 0.001) between equally obese, insulin-resistant (n = 22) and insulin-sensitive (n = 14) individuals, associated with higher fasting insulin and triglyceride and lower high-density lipoprotein cholesterol (HDL-C) concentrations in insulin-resistant individuals. Fourteen (64 %) insulin-resistant as compared with 2 (14 %) insulin-sensitive individuals were found to be at high risk for OSA by both questionnaires (p < 0.01). Whereas half of insulin-resistant individuals met the ESS criteria for excessive daytime sleepiness, only one insulin-sensitive individual did (p = 0.011). High risk for OSA and excessive daytime sleepiness is prevalent among the insulin-resistant subgroup of obese individuals. Surrogate estimates of insulin resistance based on fasting insulin, triglycerides, and/or HDL-C can be used to help identify those obese adults who would benefit most from OSA screening and referral for polysomnography.

The Association of Fasting Insulin, Glucose, and Lipids with Bone Mass in Adolescents: Findings from a Cross-Sectional Study

It is unclear whether variation in insulin resistance mediates the positive association of fat mass with bone mass in children/adolescents. Our objective was to examine whether markers linked to insulin resistance [fasting insulin, glucose, triglycerides, and high-density lipoprotein cholesterol (HDLc)] are associated with bone mass in adolescents, and if they are, to examine whether they mediate the fat mass-bone mass association. We conducted a cross-sectional analysis in participants from the Avon Longitudinal Study of Parents and Children. Participants included 2305 (1100 male) individuals of mean age 15.5 yr. We evaluated total body less head bone mineral content (BMC) (grams), bone area (BA) (square centimeters), and bone mineral density (BMD) (grams per square centimeter) from a dual-energy x-ray absorptiometry scan. Fat mass, fasting insulin, and triglycerides were positively associated with BMD, BMC, and BA; HDLc was inversely associated with these outcomes. For example, the adjusted mean difference in BMC per 1 sd fasting insulin was 45 g (95% confidence interval = 17-73 g) in males and 50 g (95% confidence interval = 28-72 g) in females. When the associations of fat mass with outcomes were adjusted for markers of insulin resistance, they were largely unchanged. Associations of triglycerides and HDLc with outcomes were attenuated to the null when they were adjusted for fat mass, whereas those of insulin changed direction; i.e. with adjustment for fat mass, higher fasting insulin was associated with lower BMD, BMC, and BA. Fasting insulin, glucose, and lipids do not appear to mediate the positive association of fat mass with bone mass in children/adolescents. The inverse association of fasting insulin with BMD, BMC, and BA once fat mass has been controlled for needs further study.

Non‐esterified fatty acid dynamics during oral glucose tolerance test in women with former gestational diabetes

Women with former gestational diabetes are at increased risk of Type 2 diabetes, which likely relates to hyperlipidaemia and ectopic lipid storage, mainly in the liver. Here, we examined the response of non-esterified fatty acid dynamics to oral glucose loading (oral glucose tolerance test). We studied women with former gestational diabetes with normal glucose tolerance (n = 60) or impaired glucose metabolism (n = 12) and compared them with healthy women after normal pregnancy (control subjects, n = 15). During a 3-h oral glucose tolerance test, glucose, insulin and non-esterified fatty acid were frequently measured to compute the area under the non-esterified fatty acid curve and parameters of β-cell function and insulin sensitivity. Through mathematical modelling, we assessed insulin sensitivity of lipolysis inhibition and the fractional non-esterified fatty acid turnover rate. We also measured some serum liver enzymes. Women with former gestational diabetes were slightly older and had greater body mass than control subjects. Subjects with impaired glucose metabolism had lower oral glucose insulin sensitivity, but higher fasting insulin and area under the non-esterified fatty acid curve, which inversely related to oral glucose insulin sensitivity and independently determined mean glycaemia. Model-derived non-esterified fatty acid parameters were lower in subjects with impaired glucose metabolism than in control subjects, particularly sensitivity of non-esterified fatty acid inhibition to insulin (2.50 ± 0.52 vs. 1.06 ± 0.20 · 10(-2) ml/μU). Also, subjects with impaired glucose metabolism had higher liver transaminases. However, all non-esterified fatty acid parameters showed only modest inverse correlation with liver transaminases. Despite greater insulinaemia, circulating non-esterified fatty acids are higher in women with former gestational diabetes than in control subjects, which likely results from reduced sensitivity of lipolysis inhibition to insulin. This parameter may serve as indicator of an early metabolic derangement in this population at risk for diabetes.

Differential effect of polyphenol-rich dark chocolate on biomarkers of glucose metabolism and cardiovascular risk factors in healthy, overweight and obese subjects: a randomized clinical trial

The association between excess cortisol and various parameters of metabolic syndrome including hypertension, insulin resistance and dyslipidaemia is increasingly recognised. The present single-blind randomised placebo-controlled cross-over study compared the effect of polyphenol-rich dark chocolate (DC) on biomarkers of glucose metabolism, lipid profile, and blood pressure (BP) in females with BMI ≥ 25 kg m(-2) (n = 21) and females with BMI < 25 kg m(-2) (n = 21). Volunteers consumed 20 g of DC containing 500 mg polyphenols or a placebo DC with negligible polyphenol-content daily for 4 weeks, separated by a 2-week washout period. Systolic BP and diastolic BP decreased after 4 weeks of polyphenol-rich DC. Placebo raised fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR) and salivary cortisol, an effect that was significantly different from polyphenol-rich DC which had a negligible effect on fasting insulin, HOMA-IR and salivary cortisol. Females with BMI ≥ 25 kg m(-2) responded less favourably to placebo than lean females and consequently had higher fasting insulin and HOMA-IR, in addition to a lower quantitative sensitivity check index (QUICKI) after ingestion of placebo compared to polyphenol-rich DC. No significant changes in lipid profile were observed. This study provides evidence for the metabolic benefits of consuming polyphenol-rich dark chocolate while demonstrating the possibility of adverse effects occurring with polyphenol-poor chocolate placebo.

Vitamin D deficiency is associated with atherosclerosis-promoting risk factor clustering but not vascular damage in children

SummaryBackgroundVitamin D has been associated with multiple cardiometabolic risk factors in children but there is a paucity of studies examining its correlation to vascular function and structure. Our objective was to determine whether there is a correlation between vitamin D, cardiometabolic risk, vascular distensibility and carotid artery intima-media thickness (CIMT) in high-risk children.Material/MethodsThis was a cross-sectional, cohort study that compared vitamin D to cardiometabolic risk factors, carotid artery distensibility, and CIMT in 74 children with multiple, modifiable atherosclerosis-promoting risk factors. Vitamin D was used as a continuous variable and also categorized as deficient (<20 ng/mL) or sufficient (≥20 ng/mL). Seven modifiable atherosclerosis-promoting risk factors were analyzed – body mass index, systolic blood pressure, total cholesterol, triglyceride, high density lipoprotein cholesterol, fasting insulin, & tobacco smoke exposure history.ResultsFor the entire cohort, vitamin D was 26.1±9.4 ng/mL (6–63 ng/mL); and the levels were deficient in 20%. The number of modifiable atherosclerosis promoting risk factors per child was 3.3±1.6. Distensibility index was 2.62±0.87% per 10 mmHg, CIMT 0.54±0.06 mm. There was an inverse correlation between vitamin D and risk factor score (r=−0.27, p=0.02); this remained significant after adjusting for age, sex, and race. There was no association between vitamin D levels and distensibility index or CIMT.ConclusionsEven though vitamin D levels were inversely correlated with cardiometabolic risk factor score in high-risk children, there are no demonstrable vascular functional or structural effects.

Prevalence and Risk Factors of Prolonged QTc Interval among Chinese Patients with Type 2 Diabetes

Objectives. The aim of this study was to evaluate the prevalence and the risk factors of prolonged QTc interval among Chinese patients with type 2 diabetes. Methods. The retrospective study included 3156 outpatients from the Diabetes Centre, the 306th Hospital of PLA, during the period from September 2003 to June 2010. QT interval was measured manually in the 12-lead conventional electrocardiogram. The QT interval corrected for heart rate (QTc) was calculated using Bazett's formula. Additional demographic and laboratory data were also collected. Potential risk factors of prolonged QTc interval were assessed using multivariable regression. Results. The prevalence of prolonged QTc interval among Chinese patients with type 2 diabetes was 30.1%. Height (OR 0.156, 95% CI 0.032~0.748), waist circumference (OR 1.025, 95% CI 1.010~1.040), diastolic blood pressure (OR 1.016, 95% CI 1.007~1.026), postprandial glucose (OR 1.040, 95% CI 1.022~1.059), fasting insulin (OR 1.014, 95% CI 1.003~1.025), and presence of microalbuminuria (OR 1.266, 95% CI 1.033~1.551) were significant risk factors. Conclusions. The prevalence of prolonged QTc interval among Chinese patients with type 2 diabetes is high. Risk factors for prolongation of QTc interval were low height, high waist circumference, increasing diastolic blood pressure levels, high postprandial glucose levels, high fasting insulin levels, and presence of microalbuminuria.

Associations of Gestational Diabetes, Existing Diabetes, and Glycosuria With Offspring Obesity and Cardiometabolic Outcomes

OBJECTIVETo assess associations of gestational diabetes, existing diabetes, and glycosuria with adiposity and cardiometabolic risk factors in offspring at adolescence.RESEARCH DESIGN AND METHODSMultivariable regression analyses were conducted in a prospective pregnancy cohort (n = 2,563–4,198 for different outcomes). Obstetric data were abstracted from clinical records. Offspring outcomes were assessed at mean age 15.5 years. Compared with those lost to follow-up, participants included in the analysis were of higher socioeconomic position. Outcomes included BMI, waist circumference, fat mass determined by dual-energy X-ray absorptiometry scan, systolic and diastolic blood pressure (sBP and dBP, respectively), fasting glucose, insulin, lipids, and C-reactive protein (CRP).RESULTSMaternal existing diabetes, gestational diabetes, and glycosuria were associated with higher offspring BMI and fat mass (z scores); however, this effect was attenuated in the confounder-adjusted model, and the CIs included the null value. Existing diabetes and gestational diabetes were associated with higher offspring fasting glucose levels (0.24 mmol/L [95% CI 0.03–0.45] and 0.20 mmol/L [0.02–0.39], respectively). Glycosuria was associated with higher fasting insulin (adjusted ratio of geometric means 1.12 [1.01–1.25]), but there were no clear associations of existing or gestational diabetes with offspring fasting insulin. There was little evidence of an association of maternal diabetes or glycosuria with offspring dBP, sBP, lipids, or CRP.CONCLUSIONSMaternal pregnancy glycosuria, gestational diabetes, and existing diabetes show some associations with higher offspring fasting glucose and insulin assessed in adolescence but are not clearly associated with a wider range of cardiometabolic risk factors.

Statins for women with polycystic ovary syndrome not actively trying to conceive.

Statins, as lipid-lowering agents with pleiotropic actions, are likely not only to improve the dyslipidaemia associated with polycystic ovary syndrome but may also exert other beneficial metabolic and endocrine effects. To assess the efficacy and safety of statin therapy for women with polycystic ovary syndrome (PCOS) who are not actively trying to conceive. We searched the following databases (from inception to week 1, July 2011): the Cochrane Menstrual Disorders and Subfertility Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE, EMBASE and CINAHL. We handsearched relevant conference proceedings and references of the identified articles for additional studies. We also contacted experts for further studies in progress. Randomised controlled trials (RCTs) comparing a statin versus placebo or statin in combination with another drug versus another drug alone in women with PCOS. Two review authors performed data collection and analysis independently. Four trials fulfilled the criteria for inclusion. They comprised a total of 244 women with PCOS receiving 12 weeks or 6 weeks of treatment. Two trials (184 women randomised) studied the effects of simvastatin and two trials (60 women randomised) studied the effects of atorvastatin. There was no good evidence that statins improved menstrual regularity, spontaneous ovulation rate, hirsutism or acne, either alone or in combination with the combined oral contraceptive pill (OCP). Nor were there any significant effects on body mass index (BMI). Statins were effective in lowering testosterone levels (nmol/L) (mean difference (MD) -0.90, 95% CI -1.18 to -0.62, P < 0.00001, 3 RCTs, 105 women) when used alone or with the OCP. Statins also improved total cholesterol, low-density lipoprotein (LDL) and triglycerides but had no significant effect on high-density lipoprotein (HDL) levels, high sensitivity (HS) C-reactive protein (HS-CRP), fasting insulin or homeostatic model assessment (HOMA) insulin resistance. No serious adverse events were reported in any of the included studies. Although statins improve lipid profiles and reduce testosterone levels in women with PCOS, there is no evidence that statins improve resumption of menstrual regularity or spontaneous ovulation, nor is there any improvement of hirsutism or acne. There is a need for further research to be performed with large sample sizes and well-designed RCTs to assess clinical outcomes.

Clinical and biochemical presentation of polycystic ovary syndrome in women between the ages of 20 and 40

The clinical features and metabolic complications of polycystic ovary syndrome (PCOS) may change with age. This study was designed to investigate the clinical and biochemical characteristics of PCOS patients between the ages of 20 and 40. The study included 781 Taiwanese women, of whom 453 were diagnosed with PCOS and 328 were non-PCOS controls. Anthropometric components, androgens, endocrine, insulin resistance, and metabolic components were measured and correlated with age. Above parameters were compared between younger and elder women with PCOS. Age had significant negative correlations with androgens (total testosterone and dehydroepiandrosterone sulfate), the modified Ferriman-Gallwey score and the prevalence of acne and hirsutism. Age had significant positive correlations with fasting glucose, cholesterol, triglycerides and low-density lipoprotein. The 453 women who fulfilled diagnostic criteria for PCOS were classified by age into two groups: Group A (20-29 years old, n= 294) and Group B (30-40 years old, n= 159). Group A had significantly higher total testosterone levels than Group B. Group B had higher fasting insulin and glucose levels, triglycerides, body mass index and waist measurements and a higher incidence of obesity than Group A. The average ovarian volume was not significantly different among the two groups. Increased age is accompanied by a decrease in the prevalence of both clinical and biochemical hyperandrogenism in women. Hyperandrogenism is the important factor for young women with PCOS; however, abdominal obesity and certain metabolic disturbances became major concerns for older women with PCOS.

The Effect of Hydro Alcoholic Nettle (Urtica dioica) Extracts on Insulin Sensitivity and Some Inflammatory Indicators in Patients with Type 2 Diabetes: A Randomized Double-blind Control Trial

Type 2 diabetes is a metabolic disorder that is strongly associated with cardiovascular risk. Inflammation is a potential risk factor for cardiovascular disease. In this study, hydro alcoholic extract of Nettle (Urtica dioica) on insulin sensitivity and some inflammatory indicators in type 2 diabetic patients were studied. A randomized double-blind clinical trial on 50 men and women with type 2 diabetes was done for 8 weeks. Patients were adjusted by age, sex and duration of diabetes, then randomly divided into two groups, an intervention and control group. They received, 100 mg kg-1nettle extract or placebo in three portions a day for 8 weeks. Interleukin 6 (IL-6), Tumor Necrosis Factor-alpha (TNF-alpha), High Sensitive C-Reactive protein (hs-CRP) and Fasting Insulin concentration were measured. Insulin Sensitivity was calculated, at the beginning and the end of the study. The data were analyzed by SPSS version 18, p<0.05 was considered significant for all variables. After 8 weeks, IL-6 and hs-CRP showed a significant decrease in the intervention group compared to the control group (p<0.05). The findings showed that the hydro alcoholic extract of nettle has decreasing effects on IL-6 and hs-CRP in patients with type 2 diabetes after eight weeks intervention.

PWD/PhJ and WSB/EiJ Mice Are Resistant to Diet-Induced Obesity But Have Abnormal Insulin Secretion

Recently, novel inbred mouse strains that are genetically distinct from the commonly used models have been developed from wild-caught mice. These wild-derived inbred strains have been included in many of the large-scale genomic projects, but their potential as models of altered obesity and diabetes susceptibility has not been assessed. We examined obesity and diabetes-related traits in response to high-fat feeding in two of these strains, PWD/PhJ (PWD) and WSB/EiJ (WSB), in comparison with C57BL/6J (B6). Young PWD mice displayed high fasting insulin levels, although they had normal insulin sensitivity. PWD mice subsequently developed a much milder and delayed-onset obesity compared with B6 mice but became as insulin resistant. PWD mice had a robust first-phase and increased second-phase glucose-stimulated insulin secretion in vivo, rendering them more glucose tolerant. WSB mice were remarkably resistant to diet-induced obesity and maintained very low fasting insulin throughout the study. WSB mice exhibited more rapid glucose clearance in response to an insulin challenge compared with B6 mice, consistent with their low percent body fat. Interestingly, in the absence of a measurable in vivo insulin secretion, glucose tolerance of WSB mice was better than B6 mice, likely due to their enhanced insulin sensitivity. Thus PWD and WSB are two obesity-resistant strains with unique insulin secretion phenotypes. PWD mice are an interesting model that dissociates hyperinsulinemia from obesity and insulin resistance, whereas WSB mice are a model of extraordinary resistance to a high-fat diet.

Calpain-10 interacts with plasma saturated fatty acid concentrations to influence insulin resistance in individuals with the metabolic syndrome

Calpain-10 protein (intracellular Ca(2+)-dependent cysteine protease) may play a role in glucose metabolism, pancreatic β cell function, and regulation of thermogenesis. Several CAPN10 polymorphic sites have been studied for their potential use as risk markers for type 2 diabetes and the metabolic syndrome (MetS). Fatty acids are key metabolic regulators that may interact with genetic factors and influence glucose metabolism. The objective was to examine whether the genetic variability at the CAPN10 gene locus is associated with the degree of insulin resistance and plasma fatty acid concentrations in subjects with MetS. The insulin sensitivity index, glucose effectiveness, insulin resistance [homeostasis model assessment of insulin resistance (HOMA-IR)], insulin secretion (disposition index, acute insulin response, and HOMA of β cell function), plasma fatty acid composition, and 5 CAPN10 single nucleotide polymorphisms (SNPs) were determined in a cross-sectional analysis of 452 subjects with MetS participating in the LIPGENE dietary intervention cohort. The rs2953171 SNP interacted with plasma total saturated fatty acid (SFA) concentrations, which were significantly associated with insulin sensitivity (P < 0.031 for fasting insulin, P < 0.028 for HOMA-IR, and P < 0.012 for glucose effectiveness). The G/G genotype was associated with lower fasting insulin concentrations, lower HOMA-IR, and higher glucose effectiveness in subjects with low SFA concentrations (below the median) than in subjects with the minor A allele (G/A and A/A). In contrast, subjects with the G/G allele with the highest SFA concentrations (above the median) had higher fasting insulin and HOMA-IR values and lower glucose effectiveness than did subjects with the A allele. The rs2953171 polymorphism at the CAPN10 gene locus may influence insulin sensitivity by interacting with the plasma fatty acid composition in subjects with MetS. This trial was registered at clinicaltrials.gov as NCT00429195.

Knockdown of NPY Expression in the Dorsomedial Hypothalamus Promotes Development of Brown Adipocytes and Prevents Diet-Induced Obesity

Hypothalamic neuropeptide Y (NPY) has been implicated in control of energy balance, but the physiological importance of NPY in the dorsomedial hypothalamus (DMH) remains unclear. Here we report that knockdown of NPY expression in the DMH by adeno-associated virus-mediated RNAi reduced fat depots in rats fed regular chow and ameliorated high-fat diet-induced hyperphagia and obesity. DMH NPY knockdown resulted in development of brown adipocytes in inguinal white adipose tissue through the sympathetic nervous system. This knockdown increased uncoupling protein 1 expression in both inguinal fat and interscapular brown adipose tissue (BAT). Consistent with the activation of BAT, DMH NPY knockdown increased energy expenditure and enhanced the thermogenic response to a cold environment. This knockdown also increased locomotor activity, improved glucose homeostasis, and enhanced insulin sensitivity. Together, these results demonstrate critical roles of DMH NPY in body weight regulation through affecting food intake, body adiposity, thermogenesis, energy expenditure, and physical activity.

The hexosamine biosynthetic pathway can mediate myocardial apoptosis in a rat model of diet-induced insulin resistance

Type 2 diabetes is characterized by deranged metabolic pathways that may result in cardiovascular complications. For example, hyperglycaemia promotes flux through the hexosamine biosynthetic pathway (HBP) leading to greater O-GlcNAcylation of target proteins, with pathophysiological outcomes. This study investigated mechanisms whereby increased HBP flux elicits myocardial apoptosis in a rat model of diet-induced hyperglycaemia/insulin resistance. Four-week-old male Wistar rats were fed a high-fat diet (86 days) after which insulin resistance was assessed vs. matched controls. Oxidative stress was evaluated, and apoptotic peptide levels, BAD phosphorylation and overall O-GlcNAcylation assessed by immunoblotting. Protein-specific O-GlcNAcylation and BAD-Bcl-2 dimerization were determined by immunoprecipitation and Western blotting. Rats consuming the high-fat diet exhibited a moderate elevation in body weight, higher fasting insulin and glucose levels, and insulin resistance vs. controls. Overall protein O-GlcNAcylation was increased in hyperglycaemic/insulin-resistant hearts. In parallel, myocardial peptide levels of apoptotic markers (caspase-3, cytochrome-c, BAD) were significantly higher with insulin resistance. To gain mechanistic insight into our findings, we evaluated O-GlcNAcylation of BAD, a pro-apoptotic Bcl-2 homolog. Here we found increased BAD O-GlcNAcylation and decreased BAD phosphorylation (Ser136) in hyperglycaemic/insulin-resistant rat hearts. These data are in agreement with competition by phosphorylation and O-GlcNAcylation for the same or neighbouring site(s) on target proteins. Moreover, we observed increased BAD-Bcl-2 dimerization in hyperglycaemic/insulin-resistant hearts. The main finding of this study is that increased apoptosis in hyperglycaemic/insulin-resistant hearts can also be mediated through HBP-induced BAD O-GlcNAcylation and greater formation of BAD-Bcl-2 dimers (pro-apoptotic).

Intra-erythrocyte Magnesium Is Associated with Gamma-Glutamyl Transferase in Obese Children and Adolescents

This study aims at determining the association between markers of hepatic injury and serum, urinary, and intra-erythrocyte magnesium concentrations and dietary magnesium intake in obese children and adolescents. In a case-control study, 42 obese children and adolescents (8-18 years) and 42 sex- and puberty-matched controls were studied. Serum, urinary, and intra-erythrocyte magnesium levels, indices of insulin sensitivity, and liver enzymes were measured. Dietary magnesium intake was assessed using a food frequency questionnaire. Obese children and adolescents exhibited insulin resistance as determined by a higher fasting insulin and the HOMA-IR (p<0.001) and lower QUICKI indices (p=0.001); in addition these subjects had significantly higher intra-erythrocyte magnesium (IEM) concentrations, than non-obese ones (3.99±1.05 vs. 3.35±1.26 mg/dL of packed cell; p=0.015). Among liver enzymes, only gamma-glutamyl transferase (GGT) was significantly higher in obese than in non-obese subjects (22.7±9.4 vs. 17.1±7.9 U/l; p=0.002). A positive association was found between GGT and IEM in both groups; however in multivariate analysis, in obese subjects, only GGT (p=0.026) and, in non-obese subjects, only age (p=0.006) remained as significant predictors of IEM. In conclusion, increased IEM concentration was seen in insulin-resistant obese children and adolescents; furthermore, serum GGT was associated with IEM, independently of body mass index and HOMA-IR.

Noninvasive predictors for liver fibrosis in patients with nonalcoholic steatohepatitis.

To evaluate certain anthropometric, clinical and laboratory features indicating liver fibrosis in nonalcoholic steatohepatitis and to establish the noninvasive markers for liver fibrosis. Eighty-one patients (40 male, 41 female) who were diagnosed with fatty liver by ultrasonographic examination and fulfilled the inclusion criteria participated in the study. Anamnesis, anthropometric, clinical and laboratory features of all cases were recorded and then liver biopsy was performed after obtaining patient consent. Steatosis, necroinflammation and liver fibrosis were examined according to age ≥ 45, gender, body mass index, central obesity, aspartate aminotransferase (AST)/alanine aminotransferase (ALT) > 1, γ-glutamyltransferase (GGT)/ALT > 1, platelet count, insulin, c-peptide levels and the presence of hypertension, diabetes, hypertriglyceridemia and insulin resistance. Eighty-one patients with non-alcoholic steatohepatitis (NASH) enrolled in the study. 69 of 81 patients were diagnosed with NASH, 11 were diagnosed with simple fatty liver and 1 was diagnosed with cirrhosis. AST/ALT > 1, GGT/ALT > 11, high serum ferritin and fasting insulin levels, the presence of diabetes, hypertension, hypertriglyceridemia and insulin resistance seemed to enhance the severity of steatosis, necroinflammation and fibrosis but these results were not statistically significant. Liver steatosis and fibrosis can occur in individuals with normal weight. There was no significant concordance between severity of liver histology and the presence of predictors for liver fibrosis including metabolic risk factors.

Elevated fasting insulin predicts the future incidence of metabolic syndrome: a 5-year follow-up study

BackgroundThere is controversy about the specific pathophysiology of metabolic syndrome (MS) but several authors have argued that hyperinsulinemia is a key feature of the cluster. We aimed to assess whether the baseline insulin levels could predict the development of MS in a well characterised cohort of otherwise healthy adults who were followed over a five year period.MethodsWe identified 2, 350 Koreans subjects who did not have MS in 2003 and who were followed up in 2008. The subjects were divided into 4 groups according to the baseline quartiles of fasting insulin, and the predictors of the incidence of MS were analyzed using multivariate regression analysis.ResultsOver the follow up period, 8.5% of the cohort developed MS. However, 16.4% of the subjects in the highest quartile of the insulin levels developed MS. In a model that included gender, age, the smoking status, the exercise level, alcohol consumption and the systolic blood pressure, the subjects in the highest quartile of the insulin levels had more than a 5 times greater risk of developing MS compared that of the subjects in the lowest quartile. This predictive importance remained significant even after correcting for all the individual features of MS.ConclusionsThese data suggest that high baseline fasting insulin levels are independent determinants for the future development of MS.

Skipping breakfast: longitudinal associations with cardiometabolic risk factors in the Childhood Determinants of Adult Health Study

The long-term effects of skipping breakfast on cardiometabolic health are not well understood. The objective was to examine longitudinal associations of breakfast skipping in childhood and adulthood with cardiometabolic risk factors in adulthood. In 1985, a national sample of 9-15-y-old Australian children reported whether they usually ate breakfast before school. During follow-up in 2004-2006, 2184 participants (26-36 y of age) completed a meal-frequency chart for the previous day. Skipping breakfast was defined as not eating between 0600 and 0900. Participants were classified into 4 groups: skipped breakfast in neither childhood nor adulthood (n = 1359), skipped breakfast only in childhood (n = 224), skipped breakfast only in adulthood (n = 515), and skipped breakfast in both childhood and adulthood (n = 86). Diet quality was assessed, waist circumference was measured, and blood samples were taken after a 12-h fast (n = 1730). Differences in mean waist circumference and blood glucose, insulin, and lipid concentrations were calculated by linear regression. After adjustment for age, sex, and sociodemographic and lifestyle factors, participants who skipped breakfast in both childhood and adulthood had a larger waist circumference (mean difference: 4.63 cm; 95% CI: 1.72, 7.53 cm) and higher fasting insulin (mean difference: 2.02 mU/L; 95% CI: 0.75, 3.29 mU/L), total cholesterol (mean difference: 0.40 mmol/L; 95% CI: 0.13, 0.68 mmol/L), and LDL cholesterol (mean difference: 0.40 mmol/L; 95% CI: 0.16, 0.64 mmol/L) concentrations than did those who ate breakfast at both time points. Additional adjustments for diet quality and waist circumference attenuated the associations with cardiometabolic variables, but the differences remained significant. Skipping breakfast over a long period may have detrimental effects on cardiometabolic health. Promoting the benefits of eating breakfast could be a simple and important public health message.

Phenotype and metabolic profile of South Asian women with polycystic ovary syndrome (PCOS): results of a large database from a specialist Endocrine Clinic

Compared with other populations, South Asians have a greater propensity to insulin resistance and the metabolic syndrome (MetS). This is the first study to determine the distribution of phenotypes of polycystic ovary syndrome (PCOS) and their relationship to the MetS among indigenous South Asians. An evaluation of the phenotype and metabolic characteristics of PCOS was conducted by recruiting consecutive women diagnosed by Rotterdam consensus criteria from an Endocrine clinic in Colombo, Sri Lanka. Prevalence of MetS was determined, in relation to the phenotypic subgroup of PCOS and compared with ethnically matched, BMI- and age-adjusted controls (n =231). Acanthosis nigricans (AN) occurred in 64.6% of women with PCOS (n= 469). MetS occurred in 30.6% of the PCOS group compared with 6.34% of controls (P = 0.0001). Those with PCOS and MetS had significantly higher median BMI, blood pressure (BP), fasting plasma glucose, insulin and triglycerides and lower high-density lipoprotein and sex hormone-binding globulin (SHBG), but similar testosterone concentrations compared with those with PCOS alone. Prevalence of MetS was similar in the four PCOS phenotypes, although oligomenorrhoeic women were more obese compared with the normal cycling hyperandrogenic group. Multivariate logistic regression confirmed age ≥35 years, BMI ≥25 kg/m(2) and AN as significant predictors of MetS in PCOS. Case-control comparisons showed that the presence of PCOS results in higher odds of having the MetS, a high waist circumference, elevated diastolic BP, abnormal fasting lipids and high fasting insulin and plasma testosterone concentrations. Young indigenous South Asians with PCOS have greater odds of being centrally obese, with a third having the MetS that bears no relationship to the androgenic phenotype. Significant predictors for MetS within the PCOS cohort are advancing age, obesity determined by the Asian cut off (BMI >25 kg/m(2)) and AN, while family history of diabetes, hyperandrogenism and elevated SHBG have no predictive value.

Plasma lipid fatty acid composition, desaturase activities and insulin sensitivity in Amerindian women

Background and aimsTwo Amerindian populations – Shuar women living in the Amazonian rain forest under traditional conditions and urbanized women in a suburb of Lima were studied. The fatty acid composition in plasma lipids and the relationships between fatty acid composition and metabolic variables were studied, as well as in a reference group of Swedish women. Methods and resultsFasting plasma was used for analyses of glucose, insulin, leptin and fatty acid composition. Women in Lima had more body fat, higher fasting insulin and leptin and lower insulin sensitivity than the Shuar women, who had insulin sensitivity similar to Swedish women. Shuar women had very high proportions (mean; SD) of palmitoleic (13.2; 3.9%) and oleic (33.9; 3.7%) acids in the plasma cholesteryl esters with very low levels of linoleic acid (29.1; 6.1 3%), as expected on a low fat, high carbohydrate diet. The estimated activity of delta 9 (SCD-1) desaturase was about twice as high in the Shuar compared with Lima women, suggesting neo lipogenesis, while the delta 5 desaturase activity did not differ. The Lima women, as well as the Swedish, showed strong positive correlations between SCD-1 activity on the one hand and fasting insulin and HOMA index on the other. These associations were absent in the Shuar women. ConclusionsThe high SCD-1 activity in the Shuar women may reflect increased lipogenesis in adipose tissue. It also illustrates how a low fat diet rich in non-refined carbohydrates can be linked to a good metabolic situation.