Homeostasis Model Assessment Levels Research Articles

SIRT3 rs11246020 Polymorphism Associated Postprandial Triglyceride Dysmetabolism.

Energy metabolism is regulated by SIRT3, no research has been done on the connection between lipid metabolism in the oral fat test and SIRT3 polymorphism. Thus, we conducted a case-control study to investigate the connection between postprandial lipid and SIRT3 polymorphism. 402 non-obese Chinese subjects were enrolled and their postprandial lipid response to oral fat tolerance test (OFTT) was observed to understand the relationship between rs11246020 gene and postprandial triglyceride metabolism. In a binary logic regression model, a protective effect of the T allele of the rs11246020 SIRT3 for postprandial hypertriglyceridemia was shown (OR=0.417, 95% CI = 0.219-0.794, p=0.008). Compared to the CC genotype, individuals with the TT+CT variant of the rs11246020 SIRT3 gene demonstrated significantly lower levels of homeostasis model assessment of insulin resistance (HOMA-IR) (p=0.04), postprandial plasma glucose (PPG) (p=0.037), fasting plasma glucose (FPG) (p=0.02), and 4-hour triglyceridemia (Tg) (p=0.032). The C allele of rs11246020 SIRT3 gene may be a risk factor to increased possibility of postprandial triglyceridemia after an oral fat test, which involved in the mechanism of glucose and insulin metabolism.

Association between polyunsaturated fatty acids intake and insulin resistance in Brazilian adolescents (ERICA Study)

ObjectiveSome studies have proposed a beneficial effect of polyunsaturated fatty acid (PUFA) intake with regard to insulin sensitivity. The aim of this study was to estimate the energy percentage and the daily PUFA intake to investigate the association between PUFAs and insulin resistance in a large sample of Brazilian adolescents. MethodsWe evaluated 37 023 adolescents ages 12 to 17 y, who were participants in ERICA (Study of Cardiovascular Risk in Adolescents). Energy percentage and PUFA daily intake were extracted from a 24-h dietary recall. The mean daily intake of total fat, median, and the respective 95% confidence intervals (95% CI) of daily intake of linoleic acid (LA), α-linolenic acid (ALA) and the ratio of LA to ALA were estimated according to sociodemographic variables. Associations of PUFA and markers of glucose homeostasis were analyzed by Poisson regression model. ResultsMean total fat intake was 30.1% of energy (95% CI, 29.9–30.4). Most participants met the current recommended values of PUFA and LA/ALA ratio ranging from 5:1 to 10:1 (80.9%, 95% CI, 79.8–81.8). ALA intake was inversely associated with higher waist circumference (prevalence ratio [PR], 0.996; 95% CI, 0.994–0.998). LA/ALA ratio ≥9:1 was significantly associated with higher levels of homeostasis model assessment of insulin resistance (HOMA-IR; PR, 1.01; 95% CI, 1.006–1.02), and ratio >10:1 also showed significant association with higher levels of HOMA-IR (PR, 1.02; 95% CI, 1.01–1.03) and glycated hemoglobin (PR, 1.14; 95% CI, 1.04–1.26). These associations remained significant after adjustment. ConclusionPromotion of ALA intake and balanced LA/ALA ratio should be considered as a possible health strategy aimed at contributing to better control of glucose homeostasis and insulin resistance in adolescents.

Effectiveness of a Lifestyle Change Program on Insulin Resistance in Yaquis Indigenous Populations in Sonora, Mexico: PREVISY.

To evaluate the effectiveness of the healthy lifestyle promotion program for Yaquis (PREVISY) on insulin resistance in the short- and medium-term periods in adults who are overweight/obese and have an increased risk for diabetes. Using a translational research design, an intervention program was implemented in a sample of 93 Yaqui adult subjects. The effectiveness of PREVISY was evaluated by comparing the levels of Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) and the Triglycerides-Glucose Index (TyG index) at 6 and 12 months using a paired t-test. Results: In the subjects who completed the program, a decrease in the HOMA-IR index (∆ = -0.91 and ∆ = -1.29, p ≤ 0.05) and the TyG index (∆ = -0.24 y ∆ = -0.20, p ≤ 0.05) was observed in the short- and medium-term period, respectively. Subjects with body weight loss ≥ 10% showed decreased levels of HOMA-IR (∆ = -3.32 and ∆ = -4.89, p ≤ 0.05) and the TyG index (∆ = -0.80 and ∆ = -0.60, p ≤ 0.05) at 6 and 12 months, respectively. A stronger benefit of the program was found in subjects with obesity (vs. overweight) and with high and very high risk of diabetes (vs. moderate risk) in IR markers (p ≤ 0.05). The PREVISY program demonstrated its effectiveness in the improvement of some markers of insulin resistance in Yaqui adults at risk of diabetes.

Associations between omega-3 fatty acids and insulin resistance and body composition in women with polycystic ovary syndrome.

BackgroundPolycystic ovary syndrome (PCOS) is strongly associated with abdominal obesity and insulin resistance and effective approaches to nutrition (e.g., omega-3 fatty acids intake) might improve the cardiometabolic risk profile. This study aimed to examine the associations of dietary and serum omega-3 fatty acids with insulin resistance (IR) and body composition among PCOS patients.MethodsA total of 185 patients with PCOS were included in our analysis. Dietary information was collected through face-to-face interviews using a 102-item food frequency questionnaire (FFQ). Serum omega-3 fatty acid levels were measured with the gas chromatography method. Body composition was measured by both dual-energy X-ray absorptiometry (DXA) and bioelectrical impedance (BIA) methods. The multivariable linear regression model was applied to analyze the associations of dietary and serum omega-3 fatty acids with the levels of Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) and body composition parameters among PCOS patients.ResultsOur results indicated that the dietary long-chain omega-3 polyunsaturated fatty acids (PUFA) intakes were negatively associated with HOMA-IR (β = –0.089, P = 0.040), fat mass (β = –0.022, P = 0.047), and body fat percentage (β = –0.026, P = 0.032). For serum biomarkers, higher total omega-3 PUFAs levels (β = –0.158, P = 0.021) and long-chain omega-3 PUFAs levels (β = –0.187, P < 0.001), particularly eicosapentaenoic acid (EPA) (β = –164, P = 0.011) and docosahexaenoic acid (DHA) (β = –0.158, P = 0.001) were also associated with decreased HOMA-IR. In addition, generally, dietary and serum long-chain omega-3 PUFA levels, DPA, and DHA levels were both positively associated with muscle mass measured by DXA; whereas serum total, long-chain and individual omega-3 PUFA levels (e.g., DPA, EPA, and DHA) were all negatively associated with fat mass and body fat percentage. These findings were further confirmed by the findings for body composition measured by the BIA method.ConclusionHigher levels of dietary and serum omega-3 PUFAs, particularly long-chain omega PUFAs (DPA and DHA), might have beneficial effects on metabolic parameters and body composition among PCOS patients.

The Relationship between HIV Duration, Insulin Resistance and Diabetes Risk

The risk of developing Type 2 Diabetes Mellitus in people living with HIV (PLWH) can be four times greater and can occur at an earlier age and even without the presence of obesity compared to those without HIV. Therefore, the purpose of this analytical cross-sectional study was to determine the relationship between HIV duration and glucose metabolism among PLWH. Eighty-two PLWH were categorized into shorter (≤15 years) or longer HIV duration (≥16 years) and then compared for differences in demographics, physical and clinical characteristics, biomarkers, and dietary intake. Compared to those with shorter HIV duration (n = 34), those with longer HIV duration (n = 48) were on average older (p = 0.02), reported lower consumption of alcohol (p = 0.05), had higher levels of homeostasis model assessment of insulin resistance (HOMA-IR, p = 0.02), were also more likely to be a woman (p = 0.06), and have higher levels of fasting insulin (p = 0.06). When adjusted for age and body weight, the levels of HOMA-IR and fasting insulin were higher (p = 0.02 and p = 0.04) with longer compared to shorter HIV duration, respectively. Longer exposure to HIV infection is associated with impaired insulin sensitivity. Continuing research aimed at the long-term effects of HIV infection and (antiretroviral therapy) is required.

Effects of muscle-specific exercises compared to existing interventions on insulin resistance among prediabetes population of South India

Background: India is among the top three countries with diabetes and prediabetes, but interventional studies on prediabetes are less compared to other developed countries. Research design and Methods: This prospective open-label randomized interventional study was conducted among newly diagnosed prediabetes in selected districts of Kerala and Tamil Nadu in South India. Participants were randomized to six treatment groups: Group 1 – walking exercise, Group 2 – muscle-specific exercise (ME), Group 3 – metformin intervention, Group 4 – metformin with muscle-specific exercise, Group 5 – antioxidant intervention, and Group 6 – antioxidants with muscle-specific exercise. Drug intervention was for 12 weeks, and the study parameters of the subjects were measured at predefined intervals. The main outcome measures were homeostasis model assessment (HOMA), glycated hemoglobin (HbA1c), fasting blood sugar (FBS), body mass index (BMI), and waist-to-hip ratio. Results: ME intervention in prediabetes significantly reduced BMI, FBS, HbA1c, and HOMA levels (P

Effect of Visfatin on Insulin Resistance in Non-Obese Adolescents

Background: Evidence base indicate that insulin resistance (IR) is common among adolescents and relatedto Diabetes Mellitus (DM). The serum visfatin is adipocytokine derived from visceral fat that may representa novel IR of metabolic syndrome include DM type II. Therefore, it is necessary to determine the role ofserum visfatin and IR in non-obese adolescent. Also this role could help to illustrated more effective earlydetection for DM type II in non-obese adolescents.Objective: The current study aimed to evaluate serum visfatin and IR in non-obese adolescents anddetermine its association.Method: In cross-sectional study we recruited 155 normal weights between aged 13-18 years. Laboratorymeasurements were included triglyceride, fasting blood sugar, insulin and visfatin, also IR index calculatedby homeostasis model assessment (HOMA). Anthropometric measurements were included height, weight,bicep and tricep skinfold thickness.Results: Most of subjects were girl 114 (73.55 %). The mean of serum visfatin level was 57.72 ng/ml (range:0.26-876.2 ng/ml) and HOMA level was 2.26 (range: 0.13-13.4). Non-obese adolescents were found IR.Serum visfatin was not statistical significant with IR (ORadj= 3.23 (95%CI: 0.84–12.45), p= 0.098). All lipidprofile (bicep, tricep skin fold thickness and triglyceride) were not affected to IR in non-obese adolescent.Conclusions: Serum visfatin in non-obese adolescent is independent to IR. IR usually occurred with obeseadolescent, but in this study also occurs with non-obese. The key point is lipid profile does not affect to IRstatus.

The Association between SOCS1-1656G>A Polymorphism, Insulin Resistance and Obesity in Nonalcoholic Fatty Liver Disease (NAFLD) Patients.

Suppressor of cytokine signaling (SOCS) proteins prevent uncontrolled cytokine signaling and appear to play a role in the pathological processes behind obesity and insulin resistance. The polymorphism of the SOCS1 gene (rs243330, −1656G>A) is associated with obesity and glucose sensitivity. To estimate the effect of this SOCS1 gene polymorphism on nonalcoholic fatty liver disease (NAFLD) susceptibility, we performed a study on 138 patients with ultrasound-confirmed NAFLD and 1000 healthy blood donors. The relationship between the SOCS1−1656G>A polymorphism and serum biochemical parameters in NAFLD was additionally investigated. The SOCS1 variant was genotyped using a dedicated TaqMan assay. The frequency of rs243330 polymorphism did not differ between patients and controls. However, in a cohort of obese individuals (BMI ≥ 30 kg/m2) the occurrence of the G allele of the SOCS1−1656G>A polymorphism was strongly associated with NAFLD (odds ratio (OR) 1.6; 95% CI,1.1–2.5; p = 0.009), and carriers of the AA genotype have lower risk of developing NAFLD (OR 0.4; 95% CI, 0.2–0.7; p = 0.004). Overweight NAFLD patients who were carriers of GG genotypes had significantly lower levels of homeostasis model assessment of insulin resistance (HOMA-IR) values (p = 0.03 vs. AA), and the obese GG homozygotes had lower serum concertation of triglyceride (GG vs. AA; p = 0.02). Serum liver enzyme activities were not modified by the presence of SOCS1 risk variants. In conclusion, the observed phenotype of overweight NAFLD patients with non-elevated levels of TG and HOMA-IR, which is associated with genetic variants of SOCS1, provides a rationale for further research on the pathophysiology of fatty liver disease.

Insulin Resistance in Nonobese Renal Allograft Recipients on Maintenance Doses of Cyclosporine or Tacrolimus

PurposeIn comparison to cyclosporine (CsA), tacrolimus (Tac) seems to be more diabetogenic in renal transplant recipients, and post-transplant diabetes mellitus is more common in patients using Tac, especially during the first year after transplantation. However, at maintenance doses, there are no comparative data of insulin resistance (IR) in patients using Tac or CsA. The purpose of this study was to investigate the IR indexes in patients on maintenance doses of CsA or Tac. MethodsForty-five nondiabetic and nonobese renal transplant recipients participated in the study (M:F, 30:15; age, 36 ± 9 years); 27 patients were on CsA, and 18 were on Tac. All had stable graft function, were transplanted at least 6 months previously, and were receiving maintenance doses of steroids (5.0 mg/d), azathioprine or mycophenolate mofetil, and calcineurin inhibitors (CsA [2.14 ± 0.46 mg/kg/d] or Tac [0.06 ± 0.03 mg/kg/d]). IR was evaluated by the homeostasis model assessment (HOMA) index and composite body insulin sensitivity index. ResultsWe did not determine any significant difference in the HOMA and composite body insulin sensitivity index levels among patients using CsA or Tac (1.5 ± 1.3 vs 1.5 ± 1.1, P > .05, and 9.9 ± 5.8 vs 14.6 ± 11.7, P > .05, respectively). There was a significant correlation between creatinine and HOMA values. ConclusionThere was no difference in IR indexes in renal transplant recipients receiving maintenance doses of either CsA or Tac.

Hypertriglyceridemic waist phenotype and abnormal glucose metabolism: a system review and meta-analysis.

This study was to perform a meta-analysis to assess the relationship between hypertriglyceridemic-waist (HTW) phenotype and abnormal glucose metabolism. The data sources were PubMed and EMBASE up to June 2018. Studies providing the relationship between HTW phenotype and abnormal glucose metabolism were included. In total, 48 eligible studies that evaluated 2,42,879 subjects were included in the meta-analysis. In the general population, the pooled odds ratios (ORs) for elevated blood glucose and diabetes related to HTW phenotype was 2.32 (95% confidence interval (CI): 1.98-2.71) and 2.69 (95% CI: 2.40-3.01), respectively. In cohort studies, the pooled OR for diabetes related to HTW phenotype was 2.89 (95% CI: 1.97-4.25) in subjects without diabetes. The levels of homeostasis model assessment of insulin resistance (HOMA-IR) in the HTW population were increased with values of mean differences (MD) 1.12 (95% CI: 0.81-1.43. P < 0.00001, I2 = 99%) in the general population and 0.89 (95% CI: 0.75-1.04, P < 0.00001, I2 = 67%) in subjects without diabetes. HTW phenotype was closely associated with increased risk of abnormal glucose metabolism. There was also a significant correlation between HTW phenotype and insulin resistance.

The Role of Visceral Adiposity Index Levels in Predicting the Presence of Metabolic Syndrome and Insulin Resistance in Overweight and Obese Patients.

Background: To investigate visceral adiposity index (VAI) levels in obese patients with and without metabolic syndrome (MetS) and its relationship with insulin resistance (IR), and define cutoff value of VAI in the determination of patients with MetS and IR. Methods: Aged between 18 and 65, 92 patients with obesity were included. Levels of homeostasis model assessment of IR (HOMA-IR) and VAI were calculated. Results: Of 92 patients, HOMA-IR and VAI levels (P < 0.001 and P < 0.001, respectively) were found to be higher in 41 (44.6%) with MetS. The cutoff value of VAI in predicting MetS was found to be 2.205. The frequency of MetS was seen as 22.2% when VAI was below this value, but if over, was found to be 66%. There was a positive correlation between VAI and HOMA-IR levels. In 36 cases (39.1%) with HOMA-IR (≥2.5), VAI was detected to be higher than those without IR, and high-density lipoprotein-cholesterol levels were lower. The cutoff value of VAI in predicting IR was found to be 2.31. While the prevalence of IR was 23.4% in those with VAI of 2.31, IR frequency in patients with equal to or greater than 2.31 was determined as 55%. Conclusion: We found that MetS was present in almost half of overweight and obese individuals, and the cutoff values of VAI in predicting the presence of MetS and IR were 2.205 and 2.31, respectively. Our study was carried out in overweight and obese Turkish individuals, and we consider that further studies including normal weight individuals and larger population are required.

The effectiveness of metformin, oral contraceptives, and lifestyle modification in improving the metabolism of overweight women with polycystic ovary syndrome: a network meta-analysis.

We designed a network meta-analysis that investigated relatively different interventions that included the effects of metformin, oral contraceptives, and lifestyle modification on the metabolic parameters of patients with polycystic ovary syndrome. In addition, we searched for eligible interventions that improved the metabolism of glucose and lipids. We searched the PubMed, EMBASE, and Cochrane Central databases from inception to May 2018. Publication types that were categorized as randomized controlled trials met our inclusion criteria. The main outcome included the homeostasis model assessment of insulin resistance, total cholesterol, low-density lipoprotein cholesterol, and total triglycerides. We performed both a pairwise meta-analysis and a network meta-analysis to evaluate the mean difference value and 95% credibility intervals, and we calculated the surface cumulative rank curve. There were a total of 12 kinds of interventions: metformin, 2 mg cyproterone acetate plus 0.05 mg ethinylestradiol (EE/CA), 0.15 mg desogestrel plus 0.03 mg ethinylestradiol (EE/DSG), and 3 mg drospirenone plus 0.03 mg ethinylestradiol (EE/DRSP), lifestyle, exercise, diet, metformin + lifestyle, metformin + diet, EE/CA + lifestyle, metformin + EE/CA, and EE/DRSP + lifestyle from the 20 eligible RCTs that were included in this study. Our meta-analysis results showed that metformin + lifestyle (MD = -2.04, 95% CrI = -3.64 to -0.41), EE/CA + lifestyle (MD = -2.23, 95% CrI = -4.11 to -0.35), and EE/DRSP + lifestyle (MD = -2.59, 95% CrI = -4.66 to -0.50) resulted in lower in the levels of total cholesterol. Women treated with metformin + lifestyle (MD = -1.82, 95% CrI = -2.88 to -0.79), EE/CA + lifestyle (MD = -2.25, 95% CrI = -3.58 to -1.08), or EE/DRSP + lifestyle (MD = -2.29, 95% CrI = -3.69 to -1.07) exhibited significantly lower low-density lipoprotein cholesterol when compared with the placebo group. There was no significant difference between any of the interventions compared with a placebo in the levels of homeostasis model assessment of insulin resistance and total triglycerides. The surface cumulative rank curve revealed that metformin + lifestyle might be the best intervention with respect to the improvement of the homeostasis model of assessment insulin resistance and EE/DRSP + lifestyle appeared to be the best intervention for the reduction of total cholesterol and low-density lipoprotein cholesterol. Moreover, the metformin + diet intervention was more effective in reducing the level of total triglycerides. For overweight polycystic ovary syndrome patients, our evidence revealed that EE/CA and EE/SRSP combined with metformin or lifestyle changes can reduce the adverse effects on glucose and lipid metabolism of the use of oral contraceptive agents alone. Conventional PCOS treatments, such as metformin, EE/CA, and EE/DRSP, combined with lifestyle control can be particularly effective in improving the homeostasis model assessment of insulin resistance and lipid metabolism.

Correlations of insulin resistance and HbA1c with cytokines IGF-1, bFGF and IL-6 in the aqueous humor of patients with diabetic cataract.

The study aimed to investigate the correlations of insulin resistance and hemoglobin A1c (HbA1c) with cytokines [insulin-like growth factor 1 (IGF-1), basic fibroblast growth factor (bFGF) and interleukin-6 (IL-6)] in the aqueous humor of patients with diabetic cataract. 59 patients with diabetic cataract and 58 patients with simple cataract treated in Jining No. 1 People´s Hospital (Jining, China) from January 2017 to February 2018, were selected randomly. The levels of homeostasis model assessment of insulin resistance (HOMA-IR) and HbAlc, as well as IGF-1, bFGF and IL-6 in the aqueous humor were compared between the two groups. The correlations of HOMA-IR and HbAlc with IGF-1, bFGF and IL-6 were analyzed. In control group, the levels of HOMA-IR and HbAlc, as well as IGF-1, bFGF and IL-6 in the aqueous humor were significantly lower than those in observation group (p<0.05). Compared with the group with HbAlc ≤ 7%, the groups with HbAlc ≥ 9% and 7% <HbAlc< 9% had increased relevant indexes. HbAlc was positively correlated with IGF-1, bFGF and IL-6 (r=0.8309, p<0.001; r=0.8968, p<0.001; r=0.8205, p<0.001). HOMA-IR had positive correlations with IGF-1, bFGF and IL-6 (r=0.9091, p<0.001; r=0.9605, p<0.001; r=0.8118, p<0.001). IGF-1 was positively related to bFGF and IL-6 (r=0.9475, p<0.001; r=0.9112, p<0.001). For patients with diabetic cataract, HOMA-IR and HbAlc were associated with IGF-1, bFGF and IL-6 in the aqueous humor. The measurement of those indexes can help to judge the disease conditions accurately, having good predictive value.

Correlation between PAI-1, leptin and ferritin with HOMA in HIV/AIDS patients

BackgroundData about correlation of interleukins (IL-1 α, IL-1 β, IFN γ, IL-2, IL-4, IL-6, IL-8, IL-10), adipocytokines (leptin, adiponectin, monocyte chemoattractant protein-1 (MCP-1), resistin, plasminogen activator inhibitor-1 (PAI-1), tumor necrosis factor alpha (TNFα), ferritin, C reactive protein (CRP) and vascular endothelial growth factor (VEGF) with homeostasis model assessment (HOMA) in HIV/AIDS patients are still limited. Therefore the aim of this study was to evaluate the possible correlations of serum levels of PAI-1, leptin and ferritin with HOMA in HIV/AIDS patients treated with combined antiretroviral therapy (cART). MethodsThis cross-sectional study included 64 HIV/AIDS patients, all Caucasians, receiving cART at the HIV/AIDS Centre, Belgrade, Serbia. PAI-1, leptin, ferritin and insulin levels were measured using the Metabolic Syndrome Array I (Randox Laboratories Ltd., London, UK), while adiponectin and resistin levels were measured using Metabolic Syndrome Array II (Randox Laboratories Ltd., London, UK), interleukins (IL-1 α, IL-1 β, IFN γ, IL-2, IL-4, IL-6, IL-8, IL-10), MCP-1, TNF-α as well as VEGF was measured using Cytokine Array I (Randox Laboratories Ltd., London, UK). Insulin resistance was determined using the homeostasis model assessment index (HOMA). Multicollinearity of independent variables in multivariate model was analyzed using Variance Inflation Factor. ResultsCorrelation analysis revealed significant correlations between HOMA and waist circumference, body mass index, patients' age, number of cART combinations and triglycerides (p = 0.001, p = 0.001, p = 0.050, p = 0.044, p = 0.002, respectively). HOMA negatively correlated with levels of high density lipoprotein (HDL) (Rho = −0.282; p = 0.025). PAI-1 (Rho = 0.334; p= 0.007) and leptin (Rho = 0.492; p = 0.001) together with ferritin (Rho = 0.396, p = 0.001) positively and significantly correlated with HOMA. Levels of IL-1 α, IL-1 β, IFN γ, IL-2, IL-4, IL-6, IL-8, IL-10, adiponectin, MCP-1, resistin, TNF-α, CRP and VEGF did not significantly correlate with HOMA. Further, multiple logistic regression showed that there is a statistically significant correlation between PAI, leptin and ferritin with HOMA levels (p = 0.042; p < 0.001, p = 0.009). ConclusionsWe showed significant correlation between PAI-1, leptin and ferritin, independently of each other with HOMA, in HIV/AIDS patients on cART.

Glycated Albumin Is a More Useful Glycation Index than HbA1c for Reflecting Renal Tubulopathy in Subjects with Early Diabetic Kidney Disease.

BackgroundThe aim of this study was to investigate which glycemic parameters better reflect urinary N-acetyl-β-D-glucosaminidase (uNAG) abnormality, a marker for renal tubulopathy, in subjects with type 2 diabetes mellitus (T2DM) subjects with normoalbuminuria and a normal estimated glomerular filtration rate (eGFR).MethodsWe classified 1,061 participants with T2DM into two groups according to uNAG level—normal vs. high (>5.8 U/g creatinine)—and measured their biochemical parameters.ResultsSubjects with high uNAG level had significantly higher levels of fasting and stimulated glucose, glycated albumin (GA), and glycosylated hemoglobin (HbA1c) and lower levels of homeostasis model assessment of β-cell compared with subjects with normal uNAG level. Multiple linear regression analyses showed that uNAG was significantly associated with GA (standardized β coefficient [β]=0.213, P=0.016), but not with HbA1c (β=−0.137, P=0.096) or stimulated glucose (β=0.095, P=0.140) after adjusting confounding factors. In receiver operating characteristic analysis, the value of the area under the curve (AUC) for renal tubular injury of GA was significantly higher (AUC=0.634; 95% confidence interval [CI], 0.646 to 0.899) than those for HbA1c (AUC=0.598; 95% CI, 0.553 to 0.640), stimulated glucose (AUC=0.594; 95% CI, 0.552 to 0.636), or fasting glucose (AUC=0.558; 95% CI, 0.515 to 0.600). The optimal GA cutoff point for renal tubular damage was 17.55% (sensitivity 59%, specificity 62%).ConclusionGA is a more useful glycation index than HbA1c for reflecting renal tubulopathy in subjects with T2DM with normoalbuminuria and normal eGFR.

Prediction of gestational diabetes mellitus at first trimester in low-risk pregnancies

ObjectiveWe aimed to assess the relationship among the sex hormone-binding globulin (SHBG), homeostasis model assessment (HOMA), glycosylated hemoglobin (HbA1c), and cholesterol panel values to predict subsequent gestational diabetes mellitus (GDM) in low-risk pregnancies. Materials and MethodsThirty-eight pregnant women with GDM and 295 low-risk pregnant women without GDM were included in this study. Maternal blood samples were obtained during the first trimester examination to determine the SHBG, HbA1c, fasting blood glucose, insulin, thyroid stimulating hormone (TSH), free thyroxine, total cholesterol, triglycerides (TG), high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol (LDL-C) levels. The variables that exhibited statistically significant differences between the groups and independent predictors for GDM were examined using logistic regression analysis. The risk of developing GDM, according to cutoff values, was determined using receiver operating characteristic (ROC) curve analysis. ResultsThe SHBG, HOMA, LDL, and TG levels were found to be the significant independent markers for GDM [adjusted odds ratio (OR) = 0.991; 95% confidence interval (CI), 0.986–995; OR = 1.56; 95% CI, 1.24–1.98; OR = 1.02; 95% CI, 1.01–1.04; and OR = 1.01; 95% CI, 1.00–1.02, respectively]. The HbA1c, body mass index, and mean arterial pressure values were nonindependent predictors of GDM. The areas under the ROC curve used to determine the predictive accuracy of SHBG, HOMA, TG, and LDL-C for development of GDM were 0.73, 0.75, 0.70, and 0.72, respectively. For a false positive rate of 5% for the prediction of GDM, the values of the sensitivities were 21.1, 26.3, 21.1, and 18.4%, respectively. ConclusionThe HOMA, SHBG, TG, and LDL-C levels are independent predictors for subsequent development of GDM in low-risk pregnancies, but they exhibit low sensitivity.

Meat Intake and Insulin Resistance in Women without Type 2 Diabetes.

Purpose. To examine the relationship between meat intake and insulin resistance (IR) in 292 nondiabetic women. Methods. IR was evaluated using the homeostasis model assessment (HOMA). Diet was assessed via 7-day weighed food records. Servings of very lean meat (VLM) and regular meat (meat) were indexed using the ADA Exchange Lists Program. Physical activity was assessed using accelerometers and body fat was measured using the Bod Pod. Results. Meat intake was directly related to HOMA (F = 7.4; P = 0.007). Women with moderate or high meat intakes had significantly higher HOMA levels than their counterparts. Adjusting for body fat weakened the relationship (F = 1.0; P = 0.3201). Odds ratio results showed that the low meat quartile had 67% lower odds of being IR (75th percentile) compared to their counterparts (OR = 0.33; 95% CI = 0.16–0.71). These findings changed little after adjusting for all covariates simultaneously (OR = 0.34; 95% CI = 0.14–0.83). Conversely, VLM intake was not related to HOMA, with or without the covariates. Conclusion. Moderate and high meat intakes are associated with increased insulin resistance in nondiabetic women. However, differences in body fat contribute significantly to the relationship. VLM is not predictive of IR. Prudence in the amount and type of meat consumed may be helpful in decreasing the likelihood of IR.

Genetic variants of the HSD11B1 gene promoter may be protective against polycystic ovary syndrome.

The HSD11B1 gene encodes the type 1 isoform of the 11-β-hydroxysteroid dehydrogenase that is responsible for the regeneration of glucocorticoids from hormonally-inactive metabolites into active forms in a tissue-specific manner. Altered activity of the enzyme, and certain genetic variants of the HSD11B1 gene, has been associated with various metabolic morbidities. In this study, our aim was to systematically test the potential role of the HSD11B1's single nucleotide polymorphisms (SNPs) in polycystic ovary syndrome (PCOS). Nine HSD11B1 SNPs were selected and genotyped using Taqman SNP assays on real-time PCR in a group of PCOS patients (n = 58) and in age-matched healthy controls (n = 64). Genotype-phenotype correlations were determined and haplotype analysis was performed. An in silico prediction for potential transcription factor binding sites was also performed. Of the 5 promoter SNPs, 3 (rs760951; rs4844880; rs3753519) were less frequent in the PCOS group compared to healthy controls. SNPs rs4844880 and rs3753519 were in a complete linkage and the mutant haplotype (AA) was less frequent in the PCOS group. No association between HSD11B1 variants and clinical, pathological findings was observed in patients, but in healthy women the rs4844880 and the AA haplotype were associated with higher levels of homeostasis model assessment of beta cell function. The polymorphic form of the rs4844880 was predicted to bind Pbx-1. Promoter SNPs of the HSD11B1 gene might exert a potential genetic protective role against the development of PCOS, possibly via their beneficial effect on carbohydrate homeostasis due to facilitation of insulin efflux from pancreatic beta-cells.

Changes in procoagulants track longitudinally with insulin resistance: findings from the Coronary Artery Risk Development in Young Adults (CARDIA) study

To examine the association between changes in procoagulants (fibrinogen factors VII and VIII and von Willebrand factor) and the risk of insulin resistance. Using data from the Coronary Artery Risk Development in Young Adults study, we followed 2398 black and white adults without diabetes, aged 25-37years at year7, to year20. Levels of fibrinogen factors VII and VIII and von Willebrand factor were divided in tertiles (low/middle/high) at years7 and 20 and four groups reflecting changes were defined: 'low' (low at years7 and 20), 'stable' (low/middle at years7 and 20, but not both low at years7 and 20), 'high' (high at year7 and low/middle at year20; or low/middle at year7 and high at year20) and 'highest' (high at years7 and 20). Linear regression models were used to evaluate 13-year changes (year20-year7) in fibrinogen level and factors VII, VIII and von Willebrand change groups in relation to insulin resistance measures. Homeostasis model assessment of insulin resistance (year20) and changes in log homeostasis model assessment of insulin resistance (year20-year7) were significantly associated with the 13-year increase in fibrinogen (P<0.001). Compared with participants in the low group, those in the high group had significantly higher levels of homeostasis model assessment of insulin resistance (year20) and changes in homeostasis model assessment of insulin resistance (year20-year7) for fibrinogen factor VII and von Willebrand factor (P<0.017). No significant associations were observed between fibrinogen VIII and insulin resistance measures. An increase in fibrinogen level and persistently high levels of factor VII and von Willebrand factor are significantly associated with increased risk of insulin resistance. These findings provide new insight into the mechanisms to explain the heightened risk for thrombosis in adults with insulin resistance/diabetes.

Evaluation of the hypothalamic‐pituitary‐gonadal axis in eugonadal men with type 2 diabetes mellitus

Men with type 2 diabetes mellitus (DM2) have lower testosterone levels and a higher prevalence of hypogonadism. It still remains unclear the mechanism by which there is a relationship between hypogonadism and DM2. The objective was to evaluate the hypothalamic-pituitary-gonadal axis at different levels in eugonadal patients with DM2. Fourteen patients with DM2 (DM2 group) and 15 subjects without DM2 (normal glucose tolerance test) as control group (CG) were included. We assessed: (i) fasting glucose, insulin, Homeostasis Model Assessment (HOMA); (ii) luteinizing hormone (LH) pulsatility through blood collections every 10min for 4h; (iii) gonadotropin-releasing hormone (GnRH) test: basal LH and 30, 60 and 90min after 100μg of i.v. GnRH; (iv) human chorionic gonadotropin (hCG) test: basal total testosterone (TT), bioavailable testosterone (BT), free testosterone (FT), estradiol (E2), bioavailable E2 (BE2) and sex hormone-binding globulin (SHBG) and 72h post 5000IU of i.m. hCG. There were no differences in age, body mass index and waist circumference between groups. Glucose was higher in the DM2 group vs. CG: 131.1±25.5 vs. 99.1±13.6mg/dL, p=0.0005. There were no difference in basal insulin, HOMA, TT, BT, FT, E2, BE2, SHBG and LH levels between groups. The DM2 group had lower LH pulse frequency vs. CG: 0.8±0.8 vs. 1.5±0.5 pulses, p=0.009. Differences in LH pulse amplitude were not found. A negative correlation was found between the number of LH pulses and glucose, r: -0.39, p=0.03. There were no differences in the response of LH to GnRH between groups nor in the response of sexual steroids and SHBG to hCG. Patients with DM2 showed lower hypothalamic pulse frequency without changes in the pituitary response to GnRH nor testicular response to hCG. Glucose levels negatively correlated with the number of LH pulses which suggests a negative effect of hyperglycaemia in the hypothalamic secretion of GnRH.