Elevated Fasting Insulin Research Articles

Abstract 4349: Identifying causal risk factors of metabolic syndrome for renal cell carcinoma. A Mendelian randomization approach

Abstract Epidemiological studies have convincingly demonstrated that several factors of the metabolic syndrome (MetS) are associated with the risk of Renal Cell Carcinoma (RCC)These factors often occur together and it is therefore challenging to disentangle their individual causal relevance in the etiology of RCC. In order to circumvent this limitation, we have applied a Mendelian randomization (MR) approach whereby genetic markers are evaluated in relation to RCC risk as unconfounded markers of the individual MetS factors. We focused on MetS parameters from which genetic instruments could be identified from large-scale genome-wide association studies (GWAS). The following MetS factors were instrumented using multiple gene-variants: general and central obesity (body mass index (BMI) and waist-to-hip ratio), elevated blood pressure (systolic and diastolic blood pressure), dyslipidemia (high and low density cholesterol, total cholesterol, and triglycerides), hyperglycemia (fasting glucose and glucose levels at 2 hours after glucose intolerance tests), and hyperinsulinemia (fasting insulin). Genetic proxies for these parameters were identified from GIANT, ICBP, GLGC and MAGIC Consortia. Summary statistics on RCC risk for instrumental SNPs of each MetS factor, including OR estimates and standard errors, were available from GWAS coordinated by the International Agency for Research on Cancer, the US National Cancer Institute, the Institute for Cancer Research UK, and the MD Anderson Cancer Center US. Together these studies comprised a total of 12,104 RCC cases and 24,999 controls from European origin that were genotyped using different genotyping platforms. Imputation was conducted on each dataset and only SNPs with an imputation quality higher than 0.6 were considered for the analyses. The causal effect of each MetS parameter on RCC risk was subsequently estimated using the MR likelihood-based approach, assuming a linear relationship between the risk factor and the outcome and a bivariate normal distribution for the genetic association estimates. The MR risk analysis using genetic instruments of the individual MetS factors indicated that elevated BMI (P: 1×10-08) and fasting insulin (P: 7×10-04)increased the risk of RCC, whereas elevated post-load glucose levels were associated with a lower risk (P: 2×10-3). The odds ratio per standard deviation increase were estimated at 1.58 (95% CI: 1.35-1.86) for BMI, 1.77 (95%CI: 1.27-2.46) for fasting insulin, and 0.62 (95%CI: 0.46-0.83) for post-load glucose. No associations were seen for genetic instruments of blood pressure or lipids. These results provide a clear support for a causal role of obesity in RCC etiology, and suggest that factors related to hyperglycemia and/or hyperinsulinemia may be involved in the causal pathway. This study may guide future efforts aiming to clarify the biological mechanisms whereby the metabolic syndrome influences RCC pathogenesis. Citation Format: Robert Carreras-Torres, Mattias Johansson, Ghislaine Scelo, Philip Haycock, Mark Purdue, Xifeng Wu, Richard Houlston, Stephen Chanock, Paul Brennan. Identifying causal risk factors of metabolic syndrome for renal cell carcinoma. A Mendelian randomization approach. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4349.

Ywhaz/14-3-3ζ Deletion Improves Glucose Tolerance Through a GLP-1-Dependent Mechanism.

Multiple signaling pathways mediate the actions of metabolic hormones to control glucose homeostasis, but the proteins that coordinate such networks are poorly understood. We previously identified the molecular scaffold protein, 14-3-3ζ, as a critical regulator of in vitro β-cell survival and adipogenesis, but its metabolic roles in glucose homeostasis have not been studied in depth. Herein, we report that Ywhaz gene knockout mice (14-3-3ζKO) exhibited elevated fasting insulin levels while maintaining normal β-cell responsiveness to glucose when compared with wild-type littermate controls. In contrast with our observations after an ip glucose bolus, glucose tolerance was significantly improved in 14-3-3ζKO mice after an oral glucose gavage. This improvement in glucose tolerance was associated with significantly elevated fasting glucagon-like peptide-1 (GLP-1) levels. 14-3-3ζ knockdown in GLUTag L cells elevated GLP-1 synthesis and increased GLP-1 release. Systemic inhibition of the GLP-1 receptor attenuated the improvement in oral glucose tolerance that was seen in 14-3-3ζKO mice. When taken together these findings demonstrate novel roles of 14-3-3ζ in the regulation of glucose homeostasis and suggest that modulating 14-3-3ζ levels in intestinal L cells may have beneficial metabolic effects through GLP-1-dependent mechanisms.

Metabolic and Endocrine Characteristics of Indian Women with Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) is one of the most common endocrinological disorders among women of reproductive age and the leading cause of female infertility. This study intends to evaluate the lipid profile, hormonal levels [free T3 (fT3), free T4 (fT4), thyroid stimulating hormone (TSH), insulin, luteinizing hormone (LH), follicle stimulating hormone (FSH), and prolactin] in PCOS women from Nellore and its surrounding districts of Andhra Pradesh, India. This cross-sectional study included 80 newly diagnosed PCOS women and an equal number of age and body mass index (BMI) matched healthy controls. We used the photometry methods to determine serum glucose levels and the lipid profile. An immunoturbidometry method was employed to measure high sensitive C-reactive protein (hsCRP). All hormonal parameters were measured using chemiluminescence immunoassays. Insulin resistance was evaluated using the homeostatic model assessment-insulin resistance (HOMA-IR) method. Statistical analysis was done using SPSS software version 20.0. The PCOS patients presented statistically higher levels of total cholesterol (TC), triglycerides (TG) and low density lipoprotein cholesterol (LDL-c, P<0.0001) when compared to those of controls. PCOS patients had elevated fasting glucose, hsCRP, fasting insulin, TSH, LH and prolactin levels (P<0.001). An increased LH/FSH ratio (>1.5) was seen in women with PCOS compared with control women. In addition, we observed a direct correlation between fasting insulin with fasting glucose and HOMA-IR. LH was inversely proportional to BMI. The present study showed a higher prevalence of insulin resistance, dyslipidemia, and hypothyroidism in PCOS women. Furthermore this study showed increased LH concentrations, a higher LH/FSH ratio, and higher prolactin levels in PCOS women.

Improvement of oral contraceptive-induced glucose dysregulation and dyslipidemia by valproic acid is independent of circulating corticosterone

Context: Cardiometabolic disorders are rapidly becoming major public health challenges. Valproic acid (VPA) is a widely prescribed anticonvulsant drug. Objective: We hypothesized that treatment with VPA would improve the regulation of glucose and atherogenic dyslipidemia through reduction in circulating corticosterone. Methods: Female Wistar rats recieved (p.o.) combined oral contraceptive (COC) containing 1.0 µg ethinylestradiol plus 5.0 µg levonorgestrel and valproic acid (VPA; 20 mg) for 8 weeks. Results: Treatment with COC led to elevated fasting blood glucose, insulin, corticosterone, triglycerides (TG), TG/HDL-cholesterol ratio, insulin resistance (IR) and impaired glucose tolerance. VPA significantly attenuated the alterations induced by COC treatment, but did not affect the corticosterone level. However, VPA treatment led to significant increases in plasma insulin, corticosterone, atherogenic lipids and impaired glucose tolerance in rats not treated with COC. Conclusion: The findings in this study suggest that VPA mitigates against the development of COC-induced insulin resistance and dyslipidemia independent of elevated circulating corticosterone.

Managing Gynecological Problems in Indian Adolescent Girls-A Challenge of 21st Century

We analyzed 100 consecutive adolescent girls, who visited our clinic at P D Hinduja National Hospital from March 2014 to February 2015. They were evaluated prospectively for various clinical presentations at every visit. The most common complaint was that of oligomenorrhoea followed by menorrhagia. Oligomenorrhoea was seen in 50% of cases. Menorrhagia was seen in 28% of cases. Other complaints included lecurrhoea, mastalgia, pruritus vulvae, breast lump, pregnancy etc. Incidence of anemia was 26% in our study group. Few suffered from hypothyroidism, hyperprolactinemia, hyperandrogenism and elevated fasting insulin. 32% girls had features of PCOS on sonography. 66% required hormonal treatment, whereas 4% had to undergo surgical intervention for various indications. Over last few years, Adolescent Gynecology has emerged as a subspecialty in developing countries. Health Professionals dealing with adolescent age group should have empathy, friendliness and non-judgmental attitude towards their patients. Confidentiality of young people should be maintained. We need to give special attention to adolescent population as they will be the citizens and parents of tomorrow!

Suppression of hyperinsulinaemia in growing female mice provides long-term protection against obesity.

Aims/hypothesisHyperinsulinaemia is associated with obesity but its causal role in the onset of obesity remains controversial. In this study, we tested the hypothesis that transient attenuation of diet-induced insulin hypersecretion in young mice can provide sustained protection against obesity throughout adult life.MethodsUsing ‘genetically humanised’ mice lacking both alleles of rodent-specific Ins1, we compared mice heterozygous for the ancestral insulin gene Ins2 with Ins2+/+ controls. Female Ins1−/−:Ins2+/− and Ins1−/−:Ins2+/+ littermates were fed chow or high-fat diet (HFD). Insulin secretion, metabolic health variables and body mass/composition were tracked for over 1 year. We examined islet function and adipose transcript levels of adipogenic, lipogenic and lipolytic genes at two time points.ResultsIn control Ins1−/−:Ins2+/+ mice, HFD resulted in elevated fasting and glucose-stimulated insulin secretion between 8 weeks and 27 weeks of age. Hyperinsulinaemia was reduced by nearly 50% in Ins1−/−:Ins2+/− mice during this period, without lasting adverse effects on glucose homeostasis. This corresponded with attenuated weight gain and adiposity. White adipose tissue from Ins1−/−:Ins2+/− mice had fewer large lipid droplets, although transcriptional changes were not detected. Importantly, Ins1−/−:Ins2+/− mice remained lighter than Ins1−/−:Ins2+/+ littermates despite reaching an equivalent degree of hyperinsulinaemia on HFD by 52 weeks.Conclusions/interpretationThese data demonstrate that attenuation of hyperinsulinaemia in young, growing female mice provides a long-lasting protection against obesity. This protection persists despite a late-onset emergence of hyperinsulinaemia in HFD-fed Ins1−/−:Ins2+/− mice. Given the evolutionary conserved roles of insulin, it is possible that suppressing hyperinsulinaemia early in life may have far-reaching consequences on obesity in full-grown adult humans.Electronic supplementary materialThe online version of this article (doi:10.1007/s00125-015-3676-7) contains peer-reviewed but unedited supplementary material, which is available to authorised users.

PWD/PhJ mice have a genetically determined increase in nutrient-stimulated insulin secretion.

PWD/PhJ (PWD) is a wild-derived inbred mouse strain unrelated to commonly studied strains, such as C57BL/6J (B6). A chromosome substitution panel with PWD chromosomes transferred into the B6 background is commercially available and will facilitate genetic analysis of this strain. We have previously shown that the PWD strain is a model of primary fasting hyperinsulinemia. To identify more specific phenotypes affected by the genetic variation in PWD compared to B6 mice, we examined physiological mechanisms that may contribute to their elevated insulin levels. PWD mice had increased nutrient-stimulated insulin secretion due to factors inherent to their pancreatic islets. Insulin secretion responses to glucose, palmitate, and the metabolic intermediate α-ketoisocaproate were increased ~2-fold in islets from PWD mice compared to B6 islets. In contrast, there were no strain differences in processes affecting insulin secretion downstream of β cell depolarization. PWD mice tended to have larger but fewer islets than B6 mice, resulting in similar insulin-staining areas and insulin content per unit of pancreatic tissue. However, pancreata of PWD mice were smaller, resulting in reduced total β cell mass and pancreatic insulin content compared to B6 mice. Combined, these data suggest that the elevated fasting insulin levels in PWD mice result from increased generation of metabolic signals leading to β cell depolarization and insulin secretion. Identification of the genetic differences underlying the enhanced nutrient-stimulated insulin secretion in this model may lead to new approaches to appropriately modulate insulin secretion for the treatment of obesity and type 2 diabetes.

Insulin and BMI as predictors of adult type 2 diabetes mellitus.

Fasting insulin concentrations are increasingly being used as a surrogate for insulin resistance and risk for type 2 diabetes (T2DM), although associations with adult outcomes are unclear. Our objective was to determine whether fasting insulin concentrations in childhood associate with later T2DM. Fasting insulin values were available from 2478 participants in the longitudinal Cardiovascular Risk in Young Finns Study at baseline age 3 to 18 years, along with data on adult T2DM (N = 84, mean age = 39.6 years). Among 3- to 6-year-olds, a 1-SD increase in fasting insulin was associated with a relative risk (RR) of 2.04 (95% confidence interval [CI], 1.54-2.70) for later T2DM, which remained significant after we adjusted for BMI and parental history of T2DM. For those aged 9 to 18 years, a 1-SD increase in insulin was associated with an RR of 1.32 (95% CI, 1.06-1.65) for T2DM, but this became nonsignificant after we adjusted for BMI and parental history of T2DM. In the latter age group, a 1-SD increase in BMI was associated with an RR of 1.45 (95% CI, 1.21-1.73) for T2DM, with adjustment for insulin and parental history of T2DM not improving this association. BMI in younger children was not associated with later T2DM. In life course analyses, those with T2DM had higher fasting insulin levels in early childhood and later adulthood but not in peripubertal years. Elevated fasting insulin concentrations in early childhood, but not adolescence, are independently associated with an elevated risk of T2DM in adulthood.

Insulin resistance in hypothyroid patients under Levothyroxine therapy: a comparison between those with and without thyroid autoimmunity.

BackgroundA chronic inflammation resulting from an imbalance between pro-inflammatory and anti-inflammatory cytokines in Hashimoto’s thyroiditis (HT) might be responsible for IR in hypothyroidism. This study was performed to investigate a probable association between autoimmune background of hypothyroidism and IR.MethodsIn this clinical study, 63 subjects with Hashimoto’s thyroiditis and 49 subjects with post-ablation hypothyroidism were enrolled. All the participants were euthyroid for more than one year through Levothyroxine therapy. Serum concentrations of Thyroid-stimulating Hormone (TSH), Free Thyroxin (FT4, FT3), Anti-Thyroid Peroxidase Antibodies (Anti-TPO Abs), Total Cholesterol (TC), HDL-Cholesterol (HDL-C), Triglyceride (TG), Fasting Blood Glucose (FBG), and insulin levels were measured and Oral Glucose Tolerance Test (OGTT) was performed for all of the subjects. Participants with anti TPO levels more than 1000 IU /ml were classified as having highly positive antibodies.ResultsNo significant differences regarding to plasma insulin, glucose and lipid concentration, were detected between subjects with and without Hashimoto’s thyroiditis. However, subjects with highly positive Anti TPO Abs had higher prevalence of elevated fasting insulin level than those with lower titers of Anti TPO Abs and subjects without autoimmune background (94.1% vs. 62.8% and 71.4% respectively, P = 0.05). Subjects with highly positive titers of Abs also had a lower serum HDL-c levels than the rest of the subjects (40.6 ± 2.1 vs. 47.2 ± 1.7 and 47.4 ± 1.4, P = 0.04).ConclusionsThere is no obvious association between thyroid autoimmunity and metabolic indexes of hypothyroid patients. Only patients with Ani TPO antibody levels more than 1000 IU/ml may experience higher insulin level and less HDL-c with the same BMI.

Glucagon-like peptide 1 stimulates insulin secretion via inhibiting RhoA/ROCK signaling and disassembling glucotoxicity-induced stress fibers.

Chronic hyperglycemia leads to pancreatic β-cell dysfunction characterized by diminished glucose-stimulated insulin secretion (GSIS), but the precise cellular processes involved are largely unknown. Here we show that pancreatic β-cells chronically exposed to a high glucose level displayed substantially increased amounts of stress fibers compared with β-cells cultured at a low glucose level. β-Cells at high glucose were refractory to glucose-induced actin cytoskeleton remodeling and insulin secretion. Importantly, F-actin depolymerization by either cytochalasin B or latrunculin B restored glucotoxicity-diminished GSIS. The effects of glucotoxicity on increasing stress fibers and reducing GSIS were reversed by Y-27632, a Rho-associated kinase (ROCK)-specific inhibitor, which caused actin depolymerization and enhanced GSIS. Notably, glucagon-like peptide-1-(7-36) amide (GLP-1), a peptide hormone that stimulates GSIS at both normal and hyperglycemic conditions, also reversed glucotoxicity-induced increase of stress fibers and reduction of GSIS. In addition, GLP-1 inhibited glucotoxicity-induced activation of RhoA/ROCK and thereby resulted in actin depolymerization and potentiation of GSIS. Furthermore, this effect of GLP-1 was mimicked by cAMP-increasing agents forskolin and 3-isobutyl-1-methylxanthine as well as the protein kinase A agonist 6-Bnz-cAMP-AM whereas it was abolished by the protein kinase A inhibitor Rp-Adenosine 3',5'-cyclic monophosphorothioate triethylammonium salt. To establish a clinical relevance of our findings, we examined the association of genetic variants of RhoA/ROCK with metabolic traits in homeostasis model assessment index of insulin resistance. Several single-nucleotide polymorphisms in and around RHOA were associated with elevated fasting insulin and homeostasis model assessment index of insulin resistance, suggesting a possible role in metabolic dysregulation. Collectively these findings unravel a novel mechanism whereby GLP-1 potentiates glucotoxicity-diminished GSIS by depolymerizing F-actin cytoskeleton via protein kinase A-mediated inhibition of the RhoA-ROCK signaling pathway.

Effect of phosphodiesterase inhibition on insulin resistance in obese individuals.

BackgroundObesity is associated with cardiometabolic disease, including insulin resistance (IR) and diabetes. Cyclic guanosine monophosphate (cGMP) signaling affects energy balance, IR, and glucose metabolism in experimental models. We sought to examine effects of phosphodiesterase‐5 inhibition with tadalafil on IR in a pilot study of obese nondiabetic individuals.Methods and ResultsWe conducted a randomized, double‐blinded, placebo‐controlled trial of adults age 18 to 50 years with obesity and elevated fasting insulin levels (≥10 μU/mL). Participants were randomized to tadalafil 20 mg daily or placebo for 3 months. Oral glucose tolerance tests were performed, and the effect of tadalafil on IR was examined. A total of 53 participants (mean age, 33 years; body mass index [BMI], 38 kg/m2) were analyzed, 25 randomized to tadalafil and 28 to placebo. In the overall sample, measures of IR did not differ between tadalafil and placebo groups at 3 months. However, in individuals with severe obesity (BMI ≥36.2 kg/m2), tadalafil use was associated with improved IR (homeostatic model assessment for IR), compared to placebo (P=0.02, respectively). Furthermore, one measure of β‐cell compensation for IR (oral disposition index) improved with tadalafil in the overall sample (P=0.009) and in the subgroup with severe obesity (P=0.01).ConclusionResults of this pilot study did not show improvements in IR with tadalafil, compared to placebo. However, tadalafil may have favorable effects on β‐cell compensation, particularly in individuals with severe obesity. Future studies evaluating the potential metabolic benefits of cGMP modulation in obesity are warranted.Clinical Trial RegistrationURL: ClinicalTrials.gov. Unique Identifier: NCT01444651.

Association of elevated fasting insulin with metabolic parameters in women with and without polycystic ovarian syndrome (PCOS)

Association of elevated fasting insulin with metabolic parameters in women with and without polycystic ovarian syndrome (PCOS)

Increasing insulin resistance among U.S. adolescents ages 12‐19: NHANES 2003‐2010 (1024.17)

Type 2 diabetes is increasingly becoming a public concern among adolescents. The aim of this study was to utilize the National Health and Examination Survey (NHANES) to assess the prevalence trends of risk factors for diabetes mellitus in US adolescents. This study observed 2,716 adolescents from ages 12 to 19 in the NHANES survey years 2003‐2006 and 2007‐2010. There was no significant change in the prevalence of diabetes and pre‐diabetes based on fasting plasma glucose values. There was also no significant change in the prevalence of obesity. However, the prevalence of elevated glycohemoglobin (HbA1c) concentrations (5.7% ‐ 6.5%) increased from 1.8% to 4.1% of the population (p&lt;0.02). This increase in elevated HbA1c was seen predominantly in normal weight adolescents (1.3% to 3.6%, P = 0.04). In addition, there was a significant increase in average fasting insulin from 11.1 uU/mL in 2003‐06 to 12.6 uU/mL in 2007‐10 (p &lt; 0.001). A significant increase in fasting insulin was only seen in normal weight adolescents (7.7uU/ml to 9.8% uU/ml, p &lt;0.001). The increase in elevated HbA1c and fasting insulin values suggests that insulin resistance is increasing among US adolescents, particularly those in the normal weight category. Despite no significant change in fasting plasma glucose, the trend of increasing fasting insulin and HbA1c concentrations is a concern for future diabetes risk.

Elevated fasting serum insulin level predicts future development of hypertension

BackgroundStudies have investigated clinical association between fasting insulin level and hypertension. However, it is still debatable whether elevated fasting insulin actually increases the risk of hypertension with the passage of time. Thus, this study was aimed at investigating the association between baseline fasting insulin level and the development of hypertension. Methods25,062 normotensive, non-diabetic Korean men participating in a medical health check-up program were followed up from 2005 until 2010. They were divided into 4 groups according to baseline fasting insulin levels (first quartile–fourth quartile). The incidence of hypertension was compared among 4 groups, and Cox proportional hazards model was used to determine if hypertension was associated with higher baseline fasting insulin level. ResultsThe incidence of hypertension increased according to the baseline fasting insulin level (first quartile: 13.3%, second quartile: 15.4%, third quartile: 17.5%, fourth quartile: 23.2%, P<0.001). Even after adjusting for multiple covariates, the HRs (95% CI) for hypertension were higher for the second (1.12; 0.96–1.31), third (1.39; 1.20–1.62) and fourth quartile group (1.75; 1.51–2.03), compared to the first quartile group, respectively (P for trend <0.001). ConclusionThe risk of hypertension was in proportion to the baseline fasting insulin level. In addition, hyperinsulinemia was an independent risk factor for the future development of hypertension. These findings suggest the value of fasting insulin level as an early predictor of hypertension.

Elevated fasting insulin level significantly increases the risk of microalbuminuria.

Microalbuminuria is significantly associated with long-term prognosis in the general population as well as in diabetic patients. It is well known that insulin resistance (IR) can induce microalbuminuria, but an elevated fasting insulin level, which is an early clinical manifestation of IR, as a risk factor for microalbuminuria has not been clarified, so we investigated the association between fasting insulin level and the development of microalbuminuria in a general population. A total of 1,192 non-diabetic Korean men without microalbuminuria in 2005 were followed until 2010. They were categorized into 3 groups according to their fasting insulin levels and monitored for the development of microalbuminuria. The incidence of microalbuminuria was compared among groups, and Cox proportional hazards models were used to calculate the hazard ratios for microalbuminuria according to the fasting insulin levels. During 4,013.0 person-years of follow-up, 51 incident cases of microalbuminuria developed between 2006 and 2010. The incidence of microalbuminuria increased in proportion to the fasting insulin levels (tertile 1: 1.8%, tertile 2: 4.5%, tertile 3: 6.5%, P<0.001). Hazard ratios for microalbuminuria also increased in proportion to the fasting insulin levels [tertile 1: reference, tertile 2: 2.44 (1.01-5.89), tertile 3: 3.30 (1.40-7.78), respectively, P for trend 0.013]. Elevated fasting insulin level was associated with the future development of microalbuminuria.

A novel mouse model of nonalcoholic steatohepatitis with significant insulin resistance

Currently available models insufficiently reflect the pathogenic alternation of nonalcoholic steatohepatitis\\NASH), such as insulin resistance. The present study aimed to characterize a novel NASH model caused by feeding the diet containing conjugated linoleic acid (CLA). In this study, mice were fed a control diet or the diet containing 0.5% CLA for 8 weeks. The insulin tolerance test (ITT) and homeostasis model assessment of insulin resistance (HOMA-IR) were used to determine the extent of insulin resistance. Liver lipotoxicity and inflammation were assessed by endoplasmic reticulum (ER) stress, autolipophagy, recruitment of Kupffer cells and hepatic stellate cell (HSC) activation. We found that liver weight was markedly increased, and histopathological examination showed marked macrosteatosis with focal hepatocellular death through apoptosis, and mild pericellular fibrosis with Kupffer cell recruitment and HSC activation, as well as light chain IIIβ-positive cells and enhanced ER stress in mice fed the CLA-containing diet. Enhanced synthesis and reduced β-oxidation of fatty acids resulted in their accumulation and lipotoxicity in hepatocytes. A biophotonic technology revealed lipid droplet accumulation in the liver from mice fed the CLA-containing diet, and Raman spectroscopic analysis indicated that these lipid droplets predominantly contained saturated fatty acids. Elevated fasting insulin levels, abnormal ITT and HOMA-IR confirmed the marked insulin resistance in these mice. Decreased phosphorylation of the insulin-signaling molecule Akt was partially responsible for the significant insulin resistance. In conclusion, Mice fed the diet containing CLA-developed steatohepatitis with marked insulin resistance, which is similar to the characteristics observed in NASH patients. The further characterization of this model would be particularly useful for revealing the critical role of insulin resistance in NASH development in conditions such as metabolic syndrome, diabetes and obesity.

The Pregnancy in Polycystic Ovary Syndrome II study: baseline characteristics and effects of obesity from a multicenter randomized clinical trial

To summarize baseline characteristics from a large multicenter infertility clinical trial. Cross-sectional baseline data from a double-blind randomized trial of two treatment regimens (letrozole vs. clomiphene). Academic Health Centers throughout the United States. Seven hundred fifty women with polycystic ovary syndrome (PCOS) and their male partners took part in the study. None. Historic, biometric, biochemical, and questionnaire parameters. Females averaged 30 years and were obese (body mass index [BMI] 35) with ∼20% from a racial/ethnic minority. Most (87%) were hirsute and nulligravid (63%). Most of the women had an elevated antral follicle count and enlarged ovarian volume on ultrasound. Women had elevated mean circulating androgens, LH-to-FSH ratio (∼2), and antimüllerian hormone levels (8.0 ng/mL). In addition, women had evidence for metabolic dysfunction with elevated mean fasting insulin and dyslipidemia. Increasing obesity was associated with decreased LH-to-FSH levels, antimüllerian hormone levels, and antral follicle counts but increasing cardiovascular risk factors, including prevalence of the metabolic syndrome. Men were obese (BMI 30) and had normal mean semen parameters. The treatment groups were well matched at baseline. Obesity exacerbates select female reproductive and most metabolic parameters. We have also established a database and sample repository that will eventually be accessible to investigators. NCT00719186.

ASSOCIATION OF C-REACTIVE PROTEIN WITH METABOLIC SYNDROME AND DEPRESSIVE SYMPTOMS IN THE ENGLISH LONGITUDINAL STUDY OF AGEING

IntroductionThe metabolic syndrome is a cluster of risk factors comprised of elevated fasting plasma glucose and insulin resistance, central obesity, low levels of high-density lipoprotein cholesterol, hypertriglyceridemia, and hypertension. Depression...

Does adiponectin play a role in gestational diabetes?

Current literature provides contradictory information on the role of adiponectin (AdipoQ) in the course of gestational diabetes (GDM). The aim of the study was to measure AdipoQ concentration in blood of women with GDM and to find relationships between this adipokine and clinical and biochemical parameters. The study group included 50 women diagnosed with GDM between 24 and 28 weeks of gestation who underwent routine prenatal tests for GDM in compliance with the guidelines of the Polish Diabetes Association. All patients underwent clinical and laboratory evaluation at GDM diagnosis. Laboratory tests included serum AdipoQ concentration, fasting glucose, fasting insulin, OGTT and lipid parameters in serum. AdipoQ concentrations did not differ significantly between the groups during gestation (p=0.7054). In the subgroup (2h glucose level in the OGTT 200 mg/dl) the concentration of AdipoQ tended to be decreased as compared to the remaining patients from the study and control groups, though the decline was insignificant (p=0.0541). The concentration of AdipoQ in the subgroup was about 20% lower than in the other patients from the study group. No correlations, except with the neonatal weight (r= - 0.29, p&lt;0.05), were found between AdipoQ and the studied parameters. The GDM group showed significantly elevated fasting glucose, insulin, HOMA-IR values, total cholesterol, LDL-cholesterol and triglicerydes, as compared with the control group (p.05). These results lead to the conclusion that women with newly diagnosed and promptly treated GDM have normal adiponectin level. A negative correlation between AdipoQ level and the birth weight may suggest that this adipokine plays a role in the control of the birth weight especially in the incidence of macrosomia.

The Prevalence of Abnormal Metabolic Parameters in Obese and Overweight Children

This retrospective study aimed to determine the prevalence of abnormal metabolic parameters in obese children and its correlation to the degree of obesity determined by body mass index (BMI). In total, 101 children seen at the Pediatric Gastroenterology Obesity Clinic at Stony Brook Children's University Hospital were enrolled in the study. The degree of obesity was characterized according to the following formula: (patient's BMI/BMI at 95th percentile) × 100%, with class I obesity >100%-120%, class II obesity >120%-140%, and class III obesity >140%. A set of metabolic parameters was evaluated in these patients. Frequency distributions of all study variables were examined using the χ(2) test of independence. Mean differences among the obesity classes and continuous measures were examined using 1-way analysis of variance. Within our study population, we found that 80% of our obese children had a low high-density lipoprotein (HDL) cholesterol level, 58% had elevated fasting insulin levels, and 32% had an elevated alanine aminotransferase (ALT) level. Class II obese children had a 2-fold higher ALT value when compared with class I children (P = .036). Fasting insulin, ALT, HDL cholesterol, and triglyceride levels trended with class of obesity. Obese children in classes II and III are at higher risk for developing abnormal laboratory values. We recommend obese children be further classified to reflect the severity of the obesity since this has predictive significance for comorbidities. Obesity classes I, II, and III could help serve as a screening tool to help communicate risk assessment.