Insulin Resistance Risk Factors Research Articles

Low Prevalence of Insulin Resistance Among Iranian Patients with Chronic Hepatitis C Virus Infection: A Case-Control Study.

Association between Chronic Hepatitis C virus (CHC) infection and type 2 diabetes mellitus has been challenging in recent decades. Despite of extensive research in this area, there is no general agreement on the direct effect of HCV infection on insulin resistance. The study was performed in 52 CHC patients (mean age = 39.48) and 52 sex-matched healthy Iranian controls, referred to the Hepatitis Clinic, Department of Gastroenterohepatology, Shiraz University of medical sciences, Shiraz, Iran, from 2012 to 2015. Fasting blood glucose level, fasting insulin level and insulin resistance defined as a Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) index were determined and compared between two groups. Insulin resistance was present in 26.9% of CHC patients and 34.62% of healthy controls. Mean HOMA index was 1.93 in patients and 2.18 in controls. There were no statistically significant differences between patient and control groups with regard to fasting insulin level, fasting blood glucose, HOMA index and insulin resistance. HOMA index and fasting insulin level were significantly higher in IR CHC patients relative to IR controls. Fasting blood glucose was also significantly higher in controls younger than 40 years. Results obtained in this study showed that chronic hepatitis C cannot be considered as a risk factor for insulin resistance and diabetes in Iranian population. However, regular screening for insulin resistance is recommended in CHC patients with age ≥ 40 years and fasting blood glucose ≥ 100 mg/dl.

Body mass index at the presentation of premature adrenarche is associated with components of metabolic syndrome at puberty.

The aim of this study was to analyze the relationship between premature adrenarche (PA) and metabolic syndrome (MeS) parameters at presentation and during puberty. This study comprised 47 girls with PA. Age- and puberty-matched 22 healthy girls without PA were the control group. Patients were evaluated at admission (first evaluation) and later in puberty (second evaluation). Anthropometric measurements, lipid levels, and hormonal parameters were studied and oral glucose tolerance test was performed. Indices for insulin resistance (IR) were calculated. The study group was divided in subgroups according to body mass index (BMI) and compared with the control group. The age of the PA group at first evaluation was 8.0 ± 1.1years; mean height SDS and BMI SDS were 0.4 ± 1.2 and 0.6 ± 0.9, respectively. Age of PA group at the second evaluation was 12.9 ± 2.4years. Frequency of obesity and overweight was 14.9 and 23.4%. Dyslipidemia ratio was 28.3%. PA group had significantly higher BMI than controls. Mean insulin concentration was higher and mean glucose and FGIR were lower in PA group and also dyslipidemia ratio was 5.3 times higher in PA than controls (p = 0.040). In PA group, overweight/obese subjects had still higher BMI at second evaluation and also higher fasting glucose, insulin, HOMA-IR. However, PA children with exaggerated DHEAS concentrations compared to those without had similar BMI SDS, insulin sensitivity, and secretion indices and lipid profile at second evaluation. BMI SDS at first evaluation was positively correlated with HOMA-IR at puberty; however, there is no correlation between DHEAS at first evaluation and HOMA-IR at puberty.Conclusion: BMI at adrenarche is more important than prepubertal adrogen concentrations such as DHEAS, while predicting the IR in puberty. Long-term follow-up of children supports the observation that PA per se may be related to IR; however, the risk increases with obesity. What is Known: • Premature adrenarche (PA) is receiving more attention as evidence emerges for a relation between early androgen excess and metabolic syndrome. • The onset of the adrenal androgen production before 8years in girls defined as PA. Pubarche, axillary hair, apocrine body odor, acne are typical phenotypic features of PA. What is New: • Body mass index at adrenarche is an important risk factor for development of insulin resistance in pubertal ages. • Degree of dehydroepiandrosterone sulfate elevation was not shown as a risk factor for insulin resistance.

Body mass index ≥23 is a risk factor for insulin resistance and diabetes in Japanese people: A brief report.

BackgroundScreening for undiagnosed type 2 diabetes mellitus is recommended for Asian Americans with a body mass index ≥23. However, the optimal body mass index cut-off score for predicting the risk of diabetes mellitus in Japanese people is not well known. The aim of this study was to determine the best body mass index cut-off score for predicting insulin resistance and diabetes mellitus in the Japanese population.MethodsThis study had two parts, a clinical investigation and a retrospective observational investigation. In the clinical part of the study, 58 participants (26 with type 2 diabetes mellitus and 32 non-diabetics) underwent a hyperinsulinemic-euglycemic clamp from which their glucose disposal rate was measured. For the retrospective part of the study, medical check-up data from 88,305 people in the Tottori Prefecture were analyzed for clinical evidence of diabetes mellitus. The optimal BMI cut-off scores for prediction of insulin resistance and diabetes mellitus were determined.ResultsIn the clamp study, the optimal body mass index cut-off score to predict insulin resistance in non-diabetic patients was 22.7. All participants with type 2 diabetes mellitus were insulin resistant, and the optimal body mass index cut-off score for prediction of severe insulin resistance was 26.2. When the data from the type 2 diabetic and the non-diabetic participants were combined, the optimal body mass index cut-off score for prediction of insulin resistance was 23.5. Analysis of 88,305 medical check-up records yielded an optimal body mass index cut-off score for prediction of diabetes mellitus of 23.6.ConclusionsThese results suggest that having a body mass index ≥23 is a risk factor for insulin resistance and diabetes mellitus in the Japanese population.

Saturated fatty acids-induced miR-424–5p aggravates insulin resistance via targeting insulin receptor in hepatocytes

The excessive intake of saturated fatty acids (SFA) causes obesity and liver steatosis, which are major risk factors for insulin resistance and type 2 diabetes. Although the expression of certain microRNAs (miRNAs) targeting the insulin signaling molecules are regulated aberrantly in SFA-induced obesity, their implications on hepatic insulin resistance are largely unknown. This study examined the associations of miR-424–5p, which is induced by SFA, with the development of insulin resistance. SFA palmitate (PA)-treated HepG2 cells and high fat diet (HFD)-induced obese mouse livers showed an impairment of insulin signaling due to a significant decrease in INSR and IRS-1 expression. Based on expression profiling and qRT-PCR analysis, miR-424–5p, which presumably targets the 3′UTR of INSR, was upregulated in both PA-treated HepG2 cells and the liver of HFD-fed mice. miR-424–5p was found to target the 3′UTR of INSR directly and downregulated INSR expression at the post-transcriptional step. Furthermore, the overexpression of miR-424–5p suppressed INSR expression significantly, leading to impaired insulin signaling and glycogen synthesis in hepatocytes. A novel mechanism for how SFA-induced miR-424–5p impairs insulin signaling through the targeting of INSR is reported. In addition, the crucial role and underlying mechanism of miR-424–5p in the obesity-induced hepatic insulin resistance is explained.

Normal Triglyceride is Associated with Insulin Resistance in the Absence of Risk Factors

BACKGROUND: Traditionally, absence of insulin resistance risk factors (IRRFs) is considered low risk for insulin resistance (IR). However, even individuals without IRRFs still have IR. This study aimed to explore the predictors of IR among the population who are non-smokers, non-diabetic and non-obese with normal blood pressure and lipids. METHODS: The data was derived from the 2007-2014 National Health and Nutrition Survey (NHANES). Participants without regular insulin resistance risk factors (IRRF-Free, n =2 317) and a subgroup without optimal insulin resistance risk factors (IRRF-Optimal, n =1 325) were involved to explore predictors of IR, which was indexed by homeostatic model assessment (HOMA). The logistic regression model and the areas under receiver operating characteristic curve (AUROC) were used to evaluate IRRFs and the predictive capacity, and Jordan index was performed to determine the optimal cut-off value of triglyceride (TG) to predict IR in IRRF-Free and IRRF-Optimal. FINDINGS: The prevalences of IR were 6.9% and 5.8% in IRRF-Free and IRRFOptimal respectively. TG and waist circumference (WC) were independently associated with the prevalence of IR (P<0·05) in both the IRRF-Free and IRRF-Optimal, where TG was positively associated with IR. The AUROC of TG was 0·7013 (95% CI 0·7011-0·7016) and 0·7180 (95% CI 0·7176-0·7183) in IRRF-Free and IRRF-Optimal respectively, and the optimal cut-off value of TG to predict IR for the two groups were both 87·5 mg/dl. INTERPRETATION: TG, even at levels currently considered normal, was independently associated with IR in the absence of IRRFs. TG can be used as an important indicator to predict the prevalence of IR. FUNDING: The Natural Science Foundation of Science and Technology Department of Jilin Province, China; the Outstanding Youth Foundation of Science and Technology Department of Jilin Province, China; the National Natural Science Foundation of China; the National Key Research and Development Program of China. DECLARATIONS OF INTERESTS: No other potential conflicts of interest relevant to this article were reported. All subjects provided written informed consent, and the study was approved by the NCHS Research Ethics Review Board (ERB).

STAT1 Ablation in CD11c+ Cells Protects Mice from Obesity-Induced Insulin Resistance

Background: Obesity is a global epidemic and major risk factor for insulin resistance and type 2 diabetes. Obesity is associated with low grade chronic inflammation of adipose tissue (AT). F4/80+CD11c+ macrophages/dendritic cells are increased and polarized into M1-like phenotypes in AT and may contribute to insulin resistance in mouse models of obesity. STAT1 is a transcription factor that play key roles in macrophage polarization into M1-like phenotypes. Hence, we investigated the role of CD11c+ macrophage/dendritic cell STAT1 in obesity-induced AT inflammation and insulin resistance. Methods: Mice with specific knockout of STAT1 in CD11c+ cells were generated by crossbreeding STAT1 fl/fl and CD11c-Cre mice. CD11c/STAT1 KO and littermate controls were fed either high fat diet (HFD, for 16 weeks) to induce obesity or normal diet (ND) as lean controls. We evaluated body composition, insulin sensitivity, gene expression of inflammatory markers, various immune cells and brown/beige adipogenesis markers in AT. Results: Perigonadal white AT (PWAT) and body weight were not significantly different between KO and control groups but liver weight and liver-to-body weight ratio were significantly reduced in obese KO mice (p&amp;lt;0.05). STAT1 KO mice on HFD exhibited improved insulin sensitivity examined by insulin tolerance test (p&amp;lt;0.05) and reduced expression of inflammatory markers TNFα, IFNγ, IL-12 and MCP1 in PWAT and subcutaneous AT (SAT) compared to littermate controls (p&amp;lt;0.05). AT immune cell analysis revealed that STAT1 ablation caused a decrease in M1-like proinflammatory polarization and increase in M2-like polarization of F4/80+ macrophages, reduced number of total CD3+ T cells and CD8+T cells in PWAT. In addition, brown/beige adipogenesis markers UCP1, CIDEA and Prdm16 also upregulated (p&amp;lt;0.05) in SAT of obese KO mice. Conclusion: Our results show the critical role of macrophage/dendritic cell STAT1 in obesity-induced AT inflammation and insulin resistance. Disclosure A. Kalathookunnel Antony: None. X.D. Perrard: None. Z. Lian: None. J. Perrard: None. L. Hennighausen: None. C.W. Smith: None. C.M. Ballantyne: Research Support; Self; Abbott, Amarin Corporation, Amgen Inc., Esperion Therapeutics, Ionis Pharmaceuticals, Inc., Novartis Pharmaceuticals Corporation, Pfizer Inc., Regeneron Pharmaceuticals, Inc., Roche Diagnostics Corporation, Sanofi. Consultant; Self; Abbott, Amarin Corporation, Amgen Inc., AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Esperion Therapeutics, Ionis Pharmaceuticals, Inc., Matinas BioPharma, Merck &amp; Co., Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Pfizer Inc., Regeneron Pharmaceuticals, Inc., Roche Diagnostics Corporation, Sanofi. H. Wu: None.

Adipose Tissue Transferrin and Insulin Resistance

Iron is an important micronutrient involved in several metabolic processes, and excessive iron is a risk factor for insulin resistance (IR) and diabetes. To define the genetic regulation of iron metabolism and its role in IR, we used gene expression, genotype, and insulin sensitivity data from an African American cohort (AAGMEx, N=256). Among the genes in a manually curated list of 62 transcripts representing iron homeostasis genes, expression of 32 in adipose tissue showed significant correlation with SI (p&amp;lt;0.01). The expression levels of transferrin (TF, β= 0.29, p=7.84 x 10-6) and ferritin heavy chain 1 (FTH1, β= -1.2, p=3.75 x 10-13) in adipose tissue were the most positively and negatively associated with SI, respectively. Observations were replicated in independent adipose tissue data sets from individuals of European ancestry (ARCA, N=99; METSIM, N=720). Among these SI-associated transcripts, the strongest cis-regulatory genetic variant (cis-eSNP) was for TF (rs6785596, β= 0.962, p=7.84 x 10-18) in adipose, but not in muscle or liver. To identify the role of TF in adipocytes, we downregulated its expression in a human adipocyte cell model (SGBS). Gene specific shRNA knockdown of TF caused differential expression (log2FC +/-0.4, probability&amp;gt;70%) of 465 genes, involved in mitochondrial function (CPT1B, UCP2), glucose transport (GLUT4), Wnt-pathway/insulin sensitivity (SFRP4, SFRP1), chemokine activity/cell-cell interaction (CXCL1, CXCL12, ICAM1), and genes with possible roles in obesity (CES1, RARRES2). Knockdown of TF mRNA in differentiated SGBS cells impaired mitochondrial respiration (49±10% reduction of maximal oxygen consumption rate) and caused a 34±4% reduction in maximal insulin-stimulated glucose uptake (p&amp;lt;0.05). In summary, genetic regulation of transferrin expression in adipose tissue plays a novel role in regulating insulin sensitivity. Disclosure D. McClain: None. N.K. Sharma: None. F. Lorenzo: None. S. Jain: None. C.D. Langefeld: None. M.E. Comeau: None. L. Salaye: None. S.K. Das: None.

Ethnicity and Common Genetic Variants Modulate Nonalcoholic Fatty Liver Disease (NAFLD) Metabolic Phenotype in Obese Youth

Background: Pediatric Nonalcoholic Fatty Liver Disease (NAFLD) represents a major risk factor for insulin resistance and type 2 diabetes in adolescents. Methods: To characterize the clinical and genetic features associated with the development of pediatric NAFLD, 503 obese adolescents (191 Caucasians, 134 African Americans, and 178 Hispanics) underwent a MRI to quantify hepatic fat content, an oral glucose tolerance test to assess glucose tolerance and insulin sensitivity, and the genotyping of three SNPs associated with NAFLD (PNPLA3 rs738409, GCKR rs1260326, and TM6SF2 rs58542926). MRI and metabolic assessments were repeated in 133 patients after 2.27±1.44 years. Results: The prevalence of NAFLD was 42.9% in Caucasians, 15.7% in African Americans, and 59.6% in Hispanics (p&amp;lt;0.0001). Compared to Caucasians and Hispanics with NAFLD, African Americans adolescents with NAFLD had higher fasting glucose (p=0.03), insulin (p=0.0004), C-peptide (p=0.04), 2-h-glucose (p=0.04), HbA1c (p&amp;lt;0.0001), and lower insulin sensitivity (p=0.03), despite similar age (p=0.34) and gender distribution (p=0.37). This translated in a higher prevalence of prediabetes and type 2 diabetes in African Americans (66.6%) compared to Caucasians (24.4%) and Hispanics (31.1%) with NAFLD (p=0.0003). Analysis of the patients without NAFLD at baseline showed that ethnicity (p=0.02), high C-peptide levels (p=0.0006), changes in z-score BMI over time (p=0.0006) and common gene variants were strong predictors of NAFLD development at follow-up (AUROC curve 0.976). Conclusions: African American obese adolescents are relatively protected from NAFLD, but are more susceptible to the deleterious effects of NAFLD on glucose metabolism. The combination of ethnicity, markers of insulin resistance and genetic factors are strong predictors of pediatric NAFLD. Disclosure D. Trico: None. S. Caprio: None. G.R. Umano: None. A. Galderisi: None. M.M. Mata: None. J. Nouws: None. B. Pierpont: None. G. Kim: None. N. Santoro: None.

DXA-Determined Regional Adiposity Relates to Insulin Resistance in a Young Adult Population with Overweight andObesity

Obesity is a well-established risk factor for insulin resistance and type 2 diabetes mellitus, and body fat distribution has important implications for this metabolic risk. In this cross-sectional study, we used dual X-ray absorptiometry body composition data from 123 young adult participants with overweight or obesity, and correlatedwith 2 indices of insulin resistance calculated from oral glucose tolerance tests. Participants were 70% women, with mean (standard error) age 30.1 (0.6) yr, body mass index (BMI) 34.0 (0.6) kg/m2, homeostatic model assessment of insulin resistance (HOMA-IR) of 2.1 (0.2), and Matsuda insulin sensitivity index (Matsuda ISI) of 5.8 (0.4). In women, the strongest correlations were observed with the android-to-gynoid ratio (r = 0.52, p < 0.001 for HOMA-IR; r = −0.46, p < 0.001 for Matsuda ISI), and these correlations remained significant after adjustment for BMI. For men, the strongest correlations were with android fat mass (r = 0.40, p = 0.01 for HOMA-IR; r = −0.37, p = 0.02 for Matsuda ISI). Visceral adipose tissue was correlated with HOMA-IR and Matsuda ISI in women, and only with Matsuda ISI in men. BMI correlated with HOMA-IR and with Matsuda ISI in both women and men. Regional adiposity determined by dual X-ray absorptiometry correlates with indices of insulin resistance in sedentary young adults with overweight and obesity.

High Adiposity Is Associated With Higher Nocturnal and Diurnal Glycaemia, but Not With Glycemic Variability in Older Individuals Without Diabetes.

It is well known that adiposity is a risk factor for insulin resistance and type 2 diabetes mellitus. In the present study, we aimed to investigate the associations of measures of adiposity with indices of glycemia and of glycemic variability over a 72-h period in non-diabetic older adults. This cross-sectional study was conducted in non-diabetic individuals from the Active and Healthy Aging Study (N = 228), Switchbox (N = 116), and the Growing Old Together Study (N = 94). Body mass index (BMI) and waist circumference were measured, and indices of glycemia and glycemic variability were derived from continuous glucose monitoring (CGM) using the Mini-Med® CGM system. Associations between adiposity and CGM were studied separately for the three cohorts, and derived estimates were subsequently meta-analyzed. After meta-analyzing the results from the separate cohorts, individuals with a higher BMI had higher levels of glycemia. Individuals with BMI between 30 and 35 kg/m2 had 0.28 mmol/L [95% confidence interval (CI): 0.12-0.44] higher 72 h-mean glucose concentration, 0.26 mmol/L (0.10-0.42) higher diurnal glucose (6:00 a.m. to 0:00 a.m.), and 0.39 mmol/L (0.19; 0.59) higher nocturnal glucose (3:00 a.m. to 6:00 a.m.) than participants with a normal weight (BMI 18.5-25 kg/m2). However, no associations were observed between higher BMI and glycemic variability. Results for glycemia and glycemic variability were similarly observed for a high waist circumference. High adiposity associates with constant higher mean glucose levels over the day in non-diabetic older adults.

Reevaluation of Protein Intake for Preterm Infants.

Growth failure caused by undernutrition is considered one of the major causes for psychomotor delay in extremely preterm infants, and the concept for "aggressive nutritional approach" is widely accepted worldwide. Based on this, postnatal early catch-up growth due to sufficient supply of nutrients including sufficient amounts of amino acids is believed to be essential for a better outcome; however, there is no definitive evidence of aggressive nutrition on better outcomes in mortality, growth, and neurodevelopment. On the contrary, epidemiological evidence suggests that low birth weight and a rapid catch-up growth after birth are major risk factors for insulin resistance and diabetes in later life; higher protein intake during postnatal period relates to higher cardiovascular risk in later life. Considering these, optimal nutrition, especially protein administration, should be reevaluated. In this review, current opinions on the nutrition for the preterm infants are surveyed. In addition, I propose a new concept for optimized protein amount for the preterm infants based on the difference of amino acid metabolism between fetuses and preterm infants.

Insulin resistance causes inflammation in adipose tissue.

Obesity is a major risk factor for insulin resistance and type 2 diabetes. In adipose tissue, obesity-mediated insulin resistance correlates with the accumulation of proinflammatory macrophages and inflammation. However, the causal relationship of these events is unclear. Here, we report that obesity-induced insulin resistance in mice precedes macrophage accumulation and inflammation in adipose tissue. Using a mouse model that combines genetically induced, adipose-specific insulin resistance (mTORC2-knockout) and diet-induced obesity, we found that insulin resistance causes local accumulation of proinflammatory macrophages. Mechanistically, insulin resistance in adipocytes results in production of the chemokine monocyte chemoattractant protein 1 (MCP1), which recruits monocytes and activates proinflammatory macrophages. Finally, insulin resistance (high homeostatic model assessment of insulin resistance [HOMA-IR]) correlated with reduced insulin/mTORC2 signaling and elevated MCP1 production in visceral adipose tissue from obese human subjects. Our findings suggest that insulin resistance in adipose tissue leads to inflammation rather than vice versa.

Chronic fructose intake does not induce liver steatosis and inflammation in female Sprague-Dawley rats, but causes hypertriglyceridemia related to decreased VLDL receptor expression.

Sugar-sweetened beverage intake is a risk factor for insulin resistance, dyslipidemia, fatty liver, and steatohepatitis (NASH). Sub-chronic supplementation of liquid fructose, but not glucose, in female rats increases liver and plasma triglycerides without inflammation. We hypothesized that chronic supplementation of fructose would cause NASH and liver insulin resistance. We supplemented female Sprague-Dawley rats with water or either fructose or glucose 10% w/v solutions under isocaloric conditions for 7months. At the end, plasma analytes, insulin, and adiponectin were determined, as well as liver triglyceride content and the expression of key genes controlling inflammation, fatty acid synthesis and oxidation, endoplasmic reticulum stress, and plasma VLDL clearance, by biochemical and histological methods. Although sugar-supplemented rats increased their energy intake by 50-60%, we found no manifestation of liver steatosis, fibrosis or necrosis, unchanged plasma or tissue markers of inflammation or fibrosis, and reduced liver expression of gluconeogenic enzymes, despite both sugars increased fatty acid synthesis, mTORC1, and IRE1 activity, while decreasing fatty acid oxidation and PPARα activity. Only fructose-supplemented rats were hypertriglyceridemic, showing a reduced expression of VLDL receptor and lipoprotein lipase in skeletal muscle and vWAT. Glucose-supplemented rats showed increased adiponectinemia, which would explain the different metabolic outcomes of the two sugars. Chronic liquid simple sugar supplementation, as the sole risk factor, is not enough for female rats to develop NASH and increased liver gluconeogenesis. Nevertheless, under isocaloric conditions, only fructose induced hypertriglyceridemia, thus confirming that also the type of nutrient matters in the development of metabolic diseases.

Altered DNA methylation in liver and adipose tissues derived from individuals with obesity and type 2 diabetes

BackgroundObesity is a well-recognized risk factor for insulin resistance and type 2 diabetes (T2D), although the precise mechanisms underlying the relationship remain unknown. In this study we identified alterations of DNA methylation influencing T2D pathogenesis, in subcutaneous and visceral adipose tissues, liver, and blood from individuals with obesity.MethodsThe study included individuals with obesity, with and without T2D. From these patients, we obtained samples of liver tissue (n = 16), visceral and subcutaneous adipose tissues (n = 30), and peripheral blood (n = 38). We analyzed DNA methylation using Illumina Infinium Human Methylation arrays, and gene expression profiles using HumanHT-12 Expression BeadChip Arrays.ResultsAnalysis of DNA methylation profiles revealed several loci with differential methylation between individuals with and without T2D, in all tissues. Aberrant DNA methylation was mainly found in the liver and visceral adipose tissue. Gene ontology analysis of genes with altered DNA methylation revealed enriched terms related to glucose metabolism, lipid metabolism, cell cycle regulation, and response to wounding. An inverse correlation between altered methylation and gene expression in the four tissues was found in a subset of genes, which were related to insulin resistance, adipogenesis, fat storage, and inflammation.ConclusionsOur present findings provide additional evidence that aberrant DNA methylation may be a relevant mechanism involved in T2D pathogenesis among individuals with obesity.

The role of Cholecalciferol in the Improvement of Insulin Resistance in Diabetic Mice Model

&#x0D; Insulin resistance is an important predictor of the incidence of diabetes mellitus. Vitamin D deficiency is one of the risk factors for insulin resistance, and there is a relationship between hypovitaminosis vitamin D with the prevalence of diabetes mellitus. Cholecalciferol is one form of vitamin D3. HOMA-IR levels are one of the parameters of insulin resistance. This study aims to prove that administration of cholecalciferol can improve insulin resistance conditions in diabetic mice model. This study used 20 mice divided into 5 groups negative control(STZ+propilen glycol), positive control (STZ+metformin), P1(STZ+cholealciferol 25ng), P2(STZ+cholealciferol 50ng), P3(STZ+cholealciferol 100ng). Mice given STZ dose 150mg / KgBB intraperitoneal to obtain hyperglycemia conditions. Administration of cholecalciferol for 14 days. The result obtained average HOMA-IR level after treatment is negative control(2,32), positive control (0,825), P1(0,975), P2(0,5), P3(0,3). The result obtained average HOMA-B level after treatment is negative control (2,76), positive control (11,92), P1 (18,4), P2(10,88), P3(35,35). The result of statistical analysis using Kruskall wallis test obtained p &lt;0,005. The conclusion of this study is that administration of cholecalciferol may improve insulin resistance in diabetic model mice. &#x0D; Keyword : cholecalciferol, HOMA-IR, HOMA-B, streptozotocin&#x0D;

Elevated Neutrophil-to-Lymphocyte Ratio in Metabolic Syndrome Is Associated with Increased Risk of Colorectal Adenoma.

Metabolic syndrome (MetS) is an important cardiovascular risk factor for insulin resistance and has been linked to colorectal adenoma via inflammation. The neutrophil-to-lymphocyte ratio (NLR) has been suggested as an important inflammatory marker. We initiated this investigation to determine the relationship between colorectal adenoma and NLR in patients with MetS. We examined participants who visited the Health Promotion Center at Kosin University Gospel Hospital, Busan, Korea. Subjects who underwent both colonoscopy and liver ultrasonography were included. Colorectal adenoma was defined as the presence of a colon polyp with a histologically adenomatous component. MetS was defined according to the modified National Cholesterol Education Program Adult Treatment Panel III definition for South Asians. Anthropometric measurements and biochemical tests of liver and metabolic function were assessed. A total of 1007 subjects were included in the study sample. Their mean age was 48.3 ± 9.7 years and 262 (26.0%) subjects had MetS, while 439 (43.6%) subjects had pathologically proven colorectal adenoma. Subjects with MetS were older, more likely to be male, and had significantly higher prevalences of colorectal adenoma (49.2% vs. 41.6%, P = 0.032), nonalcoholic fatty liver disease (62.8% vs. 19.5%, P < 0.001), and higher NLR (2.0 ± 0.9 vs. 1.7 ± 0.7, P < 0.001) compared to those without MetS. High NLR (≥2.0) was an independent factor affecting the prevalence of colorectal adenoma [odds ratio (OR) 1.38, confidence interval (95% CI) 1.02-1.88, P = 0.040], especially in subjects with MetS (OR 1.91, 95% CI 1.12-3.28, P = 0.018). High NLR was associated with increased colorectal adenomatous polyps, particularly in subjects with MetS. Screening colonoscopies for the prevention of colorectal adenoma may be warranted for patients with high NLR and MetS.

Steroidogenic Acute Regulatory Protein (StAR) Overexpression Reduces Inflammation and Insulin Resistance in Obese Mice.

Steroidogenic acute regulatory protein (StAR), a mitochondrial cholesterol delivery protein, plays a beneficial role in hyperlipidemia, NAFLD, and endothelial inflammation. Elevated circulating fatty acids and low grade inflammation are known as key risk factors of insulin resistance and type 2 diabetes. In the present study, C57BL/6J mice were fed with HFD and infected with recombinant adenovirus expressing StAR by tail-vein injection. Intraperitoneal glucose/insulin tolerance test was performed to assess the insulin sensitivity. Morphological analysis and intramuscular lipid determination were used to illustrate the adipose hypertrophy and ectopic fat accumulation in skeletal muscle. The levels of inflammatory factor and nitric oxide were determined by ELISA and classic Griess reagent methods, respectively. The fatty acids composition was analysis using gas chromatography-mass spectrometry (GC-MS). The expression of genes associated with inflammation and insulin resistance were determined by Western blotting and qPCR to elucidate the underlying mechanism. We demonstrated that StAR overexpression ameliorated insulin resistance and systemic inflammatory response with the reduction of adipose hypertrophy and intramuscular lipid in HFD-fed mice. In addition, StAR overexpression increased serum unsaturated fatty acids (UFAs) and PPARγ expression in muscle and adipose tissue of obese mice. In conclusion, StAR may activate PPARγ by increasing UFAs, which leads to a protective role in systemic inflammation and insulin resistance in obese mice. J. Cell. Biochem. 118: 3932-3942, 2017. © 2017 Wiley Periodicals, Inc.

Obesity is the main determinant of insulin resistance more than the circulating pro-inflammatory cytokines levels in rheumatoid arthritis patients

BackgroundSystemic blockade of TNF-α in Rheumatoid arthritis with insulin resistance seems to produce more improvement in insulin sensitivity in normal weight patients with Rheumatoid arthritis than in obese patients with Rheumatoid arthritis, suggesting that systemic-inflammation and obesity are independent risk factors for insulin resistance in Rheumatoid arthritis patients. ObjectivesTo evaluate the insulin resistance in: normal weight patients with Rheumatoid arthritis, overweight patients with Rheumatoid arthritis, obese Rheumatoid arthritis patients, and matched control subjects with normal weight and obesity; and its association with major cytokines involved in the pathogenesis of the disease. MethodsAssessments included: body mass index, insulin resistance by Homeostasis Model Assessment, ELISA method, and enzymatic colorimetric assay. ResultsOutstanding results from these studies include: (1) In Rheumatoid arthritis patients, insulin resistance was well correlated with body mass index, but not with levels of serum cytokines. In fact, levels of cytokines were similar in all Rheumatoid arthritis patients, regardless of being obese, overweight or normal weight (2) Insulin resistance was significantly higher in Rheumatoid arthritis with normal weight than in normal weight (3) No significant difference was observed between insulin resistances of Rheumatoid arthritis with obesity and obesity (4) As expected, levels of circulating cytokines were significantly higher in Rheumatoid arthritis patients than in obesity. ConclusionsObesity appears to be a dominant condition above inflammation to produce IR in RA patients. The dissociation of the inflammation and obesity components to produce IR suggests the need of an independent therapeutic strategy in obese patients with RA.

Serum Osteoprotegerin Is a Potential Biomarker of Insulin Resistance in Chinese Postmenopausal Women with Prediabetes and Type 2 Diabetes.

The aim of this study is to investigate the circulating OPG levels in postmenopausal women with diabetes and prediabetes and explore the relationships between serum OPG and insulin resistance. A total of 271 unrelated Chinese postmenopausal women were recruited in this study. The subjects were divided into type 2 diabetes mellitus (T2DM) group (n = 93), impaired glucose regulation (IGR) (n = 90), and normal glucose regulation group (NGR) (n = 88), according to different glucose regulation categories. Serum OPG levels were measured by enzyme-linked immunosorbent assay. The serum OPG concentration in NGR group, 151.00 ± 45.72 pg/mL, was significantly lower than that in IGR group (169.28 ± 64.91 pg/mL) (p = 0.031) and T2DM group (183.20 ± 56.53 pg/mL) (p < 0.01), respectively. In multiple linear regression analysis, HOMA-IR, age, 2hPG, AST, ALP, and eGFR were found to be independent predictors of OPG. Increased serum OPG levels (OR = 1.009, p = 0.006) may be a risk factor for insulin resistance. The present study suggests that OPG might be implicated in the pathogenesis of diabetes and is a potential biomarker of insulin resistance in subjects with diabetes and prediabetes.

Nonalcoholic Fatty Liver Disease and Associated Metabolic Risks of Hypertension in Type 2 Diabetes: A Cross-Sectional Community-Based Study.

The mechanisms facilitating hypertension in diabetes still remain to be elucidated. Nonalcoholic fatty liver disease (NAFLD), which is a higher risk factor for insulin resistance, shares many predisposing factors with diabetes. However, little work has been performed on the pathogenesis of hypertension in type 2 diabetes (T2DM) with NAFLD. The aim of this study is to investigate the prevalence of hypertension in different glycemic statuses and to analyze relationships between NAFLD, metabolic risks, and hypertension within a large community-based population after informed written consent. A total of 9473 subjects aged over 45 years, including 1648 patients with T2DM, were enrolled in this cross-sectional study. Clinical and biochemical parameters of all participants were determined. The results suggested that the patients with prediabetes or T2DM were with higher risks to have hypertension. T2DM with NAFLD had significantly higher levels of blood pressure, triglyceride, uric acid, and HOMA-IR than those without NAFLD. Data analyses suggested that hypertriglyceridemia [OR = 1.773 (1.396, 2.251)], NAFLD [OR = 2.344 (1.736, 3.165)], hyperuricemia [OR = 1.474 (1.079, 2.012)], and insulin resistance [OR = 1.948 (1.540, 2.465)] were associated with the higher prevalence of hypertension independent of other metabolic risk factors in type 2 diabetes. Further studies are needed to focus on these associations.