The association of insulin resistance measured through the estimated glucose disposal rate with predictors of micro-and macrovascular complications in patients with type 1 diabetes

Background and aimInsulin resistance (IR) is associated with a higher rate of type 1 diabetes (T1D) complications. We aimed to examine the relationship between estimated glucose disposal rate (eGDR), a readily available marker of IR in clinical practice and early predictor biomarkers of macrovascular and microvascular complications in patients with T1D.DesignA cross-sectional study.MethodsA total of 165 consecutive patients with T1D free of cardiovascular, eye, and renal complications were included in the study from 2016 to 2020. Participants were characterized as insulin resistant if their eGDR value was ≤ 8 mg/kg/min. Pulse wave velocity (PWV) and global longitudinal strain (GLS) were used as surrogates for subclinical atherosclerosis and left ventricular systolic dysfunction (LVSD), respectively. Four previously standardized tests based on the calculation of heart rate variability (HRV) were used to evaluate subclinical cardiac autonomic neuropathy (CAN). Early nephropathy was assessed by assessing urinary albumin to creatinine ratio (ACR).ResultsThe population sample (n = 165) included a majority of female patients (63%) and had a median age of 32 years (24?43), median disease duration of 14 years ( ± 9.5–21.5), a median BMI value of 23.7 kg/m² (21.4–26.6), an HbA1C of 7.2% (6.7–8.2) and median eGDR (lower values indicate higher insulin resistance) of 9.2 mg/kg/min (8.2–9.9), while 21.8% (n = 36) of the participants were characterized as insulin resistant. After adjustment for age, gender, and the duration of diabetes, the presence of IR was significantly associated with higher prevalence of subclinical atherosclerosis (OR:2.59, 95% CI: 1.06–6.30, p = 0.036), CAN (OR:3.07, 95% CI: 1.02–9.32, p = 0.047) and subclinical LVSD (OR: 4.9, 95% CI: 1.94–12.79, p = 0.001). No association was shown with ACR.ConclusionsIn patients with T1D, insulin resistance, as measured by eGDR, correlates well with early CVD predictors and CAN. These associations appear independent of the effects of gender, aging, and disease duration.     

Mechanisms of stress,energy homeostasis and insulin resistance in European adolescents – the HELENA study

Background and aimsStress is hypothesized to facilitate the development of obesity, whose the foundations are already set during childhood and adolescence. We investigated the relationship between the stress-system, selected mechanisms of energy homeostasis and insulin resistance (IR) in a sample of European adolescents.Methods and resultsWithin HELENA-CSS, 723 adolescents (12.5–17.5 years) from 10 European cities provided all the necessary data for this study. Fasting blood samples were collected for cortisol, leptin, insulin and glucose analysis. HOMA-IR was calculated from insulin and glucose concentrations. Adolescents' body fat (BF) %, age and duration of exclusive breastfeeding were assessed. For boys and girls separately, the relationship of cortisol with leptin, insulin, glucose and HOMA-IR was examined by computing Pearson correlation coefficients and Hierarchical Linear Models (HLMs), with ‘city’ as cluster unit, adjusting for age, BF% and duration of exclusive breastfeeding. In boys, Pearson correlation coefficients illustrated positive correlations of cortisol with insulin (r = 0.144; p = 0.013), glucose (r = 0.315; p < 0.001) and HOMA-IR (r = 0.180; p = 0.002), whilst in girls, this positive relationship was observed for leptin (r = 0.147; p = 0.002), insulin (r = 0.095; p = 0.050) and HOMA-IR (r = 0.099; p = 0.041), but not for glucose (r = 0.054; p = 0.265). Observed associations were independent of adolescents' age, BF% and duration of exclusive breastfeeding after computing HLMs.ConclusionThis study suggests that the stress-system is positively related to mechanisms of energy homeostasis and IR in European adolescents, and reveals a potential small gender difference in this relationship. The hypothesis that stress might facilitate the development of obesity during adolescence is supported.     

Common variants in SOCS7 gene predict obesity,disturbances in lipid metabolism and insulin resistance

Background and aimsSpecific Suppressor of Cytokine Signaling (SOCS) members, such as SOCS7, may play a role in the development of insulin resistance (IR) owing to their ability to inhibit insulin signaling pathways. The objective was to explore the association between common variants and related haplotypes in SOCS7 gene and metabolic traits related to obesity, lipid metabolism and IR.Methods and Results780 unrelated men were included in a cross-sectional study. We selected three tagged SNPs that capture 100% of SNPs with minor allele frequency ≥ 0.10. Analyses were done separately for each SNP and followed up by haplotype analysis. rs8074124C was associated with both obesity (p = 0.005) and abdominal obesity (p = 0.002) and allele C carriers showed, in comparison with TT carriers, lower BMI (p = 0.001) and waist circumference (p = 0.001). rs8074124CC- carriers showed lower fasting insulin (p = 0.017) and HOMA-IR (p = 0.018) than allele T carriers. rs12051836C was associated with hypertriglyceridemia (p = 0.009) and hypertriglyceridemic waist (p = 0.006). rs12051836CC- carriers showed lower fasting insulin (p = 0.043) and HOMA-IR (p = 0.042). Haplotype-based association analysis (rs8074124 and rs12051836 in that order) showed associations with lipid and obesity -related phenotypes, consistent with single locus analysis. Haplotype analysis also revealed association between haplotype CT and both decreased HDL-C (p = 0.026) and HDL-C (p = 0.014) as a continuous variable.ConclusionsWe found, for the first time, significant associations between SOCS7 common variants and related haplotypes and obesity, IR and lipid metabolism disorders.     

The SH2B1 obesity locus and abnormal glucose homeostasis: Lack of evidence for association from a meta-analysis in individuals of European ancestry

Background/AimsThe development of type 2 diabetes (T2D) is influenced both by environmental and by genetic determinants. Obesity is an important risk factor for T2D, mostly mediated by obesity-related insulin resistance. Obesity and insulin resistance are also modulated by the genetic milieu; thus, genes affecting risk of obesity and insulin resistance might also modulate risk of T2D.Recently, 32 loci have been associated with body mass index (BMI) by genome-wide studies, including one locus on chromosome 16p11 containing the SH2B1 gene. Animal studies have suggested that SH2B1 is a physiological enhancer of the insulin receptor and humans with rare deletions or mutations at SH2B1 are obese with a disproportionately high insulin resistance. Thus, the role of SH2B1 in both obesity and insulin resistance makes it a strong candidate for T2D. However, published data on the role of SH2B1 variability on the risk for T2D are conflicting, ranging from no effect at all to a robust association.MethodsThe SH2B1 tag SNP rs4788102 (SNP, single nucleotide polymorphism) was genotyped in 6978 individuals from six studies for abnormal glucose homeostasis (AGH), including impaired fasting glucose, impaired glucose tolerance or T2D, from the GENetics of Type 2 Diabetes in Italy and the United States (GENIUS T2D) consortium. Data from these studies were then meta-analyzed, in a Bayesian fashion, with those from DIAGRAM+ (n = 47,117) and four other published studies (n = 39,448).ResultsVariability at the SH2B1 obesity locus was not associated with AGH either in the GENIUS consortium (overall odds ratio (OR) = 0.96; 0.89–1.04) or in the meta-analysis (OR = 1.01; 0.98–1.05).ConclusionOur data exclude a role for the SH2B1 obesity locus in the modulation of AGH.     

Defining a cutoff point for vitamin D deficiency based on insulin resistance in children

BackgroundVitamin D deficiency is a common worldwide problem. Low levels of serum 25-hydroxy vitamin D [25(OH)D], as a marker of vitamin D deficiency, have been linked to a wide field of health problems, including metabolic diseases such as insulin resistance, type 1 and type 2 DM. There is no universal definition for cutoff value of vitamin D deficiency and it seems that it varies in different populations.ObjectiveMost previous studies have used a start rise of PTH as a criteria to detect threshold of serum 25(OH)D, However, the aim of this study was to determine a cutoff point of serum 25(OH)D for vitamin D deficiency based on HOMA-IR.Materials and methodsTwo hundred and ninety seven healthy children (aged 7–11 years) were enrolled. Serum 25(OH)D and PTH were measured and HOMA-IR was calculated. The ROC curve was utilized to obtain a cutoff of vitamin D deficiency based on HOMA-IR.Results25(OH)D concentrations were inversely correlated with HOMA-IR levels (Spearman's r = ?0.14, p = 0.016). Serum 25(OH)D cutoff point was 11.6 ng/mL (29 nmol/L) in relation with HOMA-IR >2.1. By using this cutoff value, the prevalence of vitamin D deficiency was 43.4% in this study population of healthy children.ConclusionWe found that serum 25(OH)D levels are inversely associated with insulin resistance. These results suggest that in MetS patients it may benefit to determine cutoff value of 25(OH)D levels based on HOMA-IR.     

The associations between physical activity,health-related quality of life,regimen adherence,and glycemic control in adolescents with type 1 diabetes: A cross-sectional study

BackgroundAdolescents with Type 1 Diabetes (T1D) display a greater than two-fold higher risk of developing diabetes-related complications compared with their healthy peers and the risk increases markedly as glycated hemoglobin (HbA1c) increases. The majority of the known factors associated with improved glycemic control in adolescents with T1D are geared toward Western populations. Therefore, this study examined the associations between Physical Activity (PA), Health-Related Quality of Life (HRQoL), and regimen adherence on glycemic control in a Middle Eastern population of adolescents with T1DMethodsThe study utilized a cross-sectional design of Jordanian adolescents (aged 12–18) with T1D (n = 74). Self-reported measures used were the Pediatric Quality of Life-Diabetes Module, the International Physical Activity Questionnaire, and the Summary of Diabetes Self-Care Activities. HbA1c values were obtained from the medical records. Correlation analyses were conducted using Pearson’s and Spearman’s correlation tests. Multiple regression analyses were conducted to determine if HRQoL, PA, and regimen adherence predict glycemic control.ResultsOnly 14.8 % of the participants demonstrated good glycemic control (HbA1c ≤ 7.5 %). Participants with poor control had a statistically significant lower mean PA of MET-minutes/week (3531.9 ± 1356.75 vs. 1619.81 ± 1481.95, p < .001) compared to those with good control. The total sample was found to demonstrate low HRQoL (47.70 ± 10.32). Participants were within the acceptable range of PA (1885.38 ± 1601.13) MET-minutes/week. HbA1c significantly inversely correlated with PA (r = −0.328, p = .010) and regimen adherence (r = −0.299, p = .018). The regression analysis revealed that PA significantly predicted glycemic control (β = −0.367, p < .01) as adherence (β = −0.409, p < .01) and disease duration did (β = 0.444, p < .01).ConclusionBetter glycemic control was significantly associated with higher PA and regimen adherence levels. The correlation between PA and glycemic control depends highly on the level of regimen adherence or arguably, adherence acts as a buffer in the correlation between PA and glycemic control. There was no significant association between glycemic control and HRQoL.     

Plasma adiponectin levels are related to obesity,inflammation, blood lipids and insulin in type 2 diabetic and non-diabetic Trinidadians

AimsTo determine the relationship between plasma adiponectin levels and obesity, inflammation, blood lipids and insulin resistance in type 2 diabetics (T2DM) and non-diabetics in a patient population in Trinidad.MethodsA cohort study of a total of 126 type 2 diabetic (42 males and 84 females) and 140 (43 males and 97 females) non-diabetic public clinic attendees were assessed between December 2008 and July 2009. Along with clinical history and anthropometry, adiponectin, TNF-α, IL-6, CRP, lipid profile, glucose, and insulin were measured in fasting blood samples and insulin resistance (HOMA-IR) was calculated.ResultsDiabetics had higher (p < 0.05) glucose, insulin, HOMA-IR, triglycerides (TG), VLDL and systolic blood pressure than non-diabetics, but lower (p < 0.05) HDL and adiponectin levels. Adiponectin levels were lower (p < 0.05) in obese than in non-obese individuals regardless of diabetic status. There were significant gender differences in HDL, LDL and TG. Among non-obese persons, adiponectin correlated negatively with triglycerides (r = ?0.280; adiponectin), IL-6 (r = ?0.216; p < 0.005), HOMA-IR (r = ?0.373; p = 000) and positively correlated with HDL (r = 0.355; p = 0.000). Diabetic status (p = 0.025), TNF-α (p = 0.048) and BMI (p = 0.027) were identified as useful predictors of adiponectin by multiple linear regression methods. In addition binary logistic regression analysis found glucose (p = 0.001) and adiponectin (p = 0.047) to be useful indicators of type 2 diabetes.ConclusionsAdiponectin decreases with increasing adiposity and insulin resistance. Adiponectin and TNF-α appear to be related to differences in the insulin mediated glucose turnover.     

The role of vitamin D,obesity and physical exercise in regulation of glycemia in Type 2 Diabetes Mellitus patients

AimThe aims of this study were to determine the role of vitamin D, obesity and physical exercise in the regulation of glycemia in Type 2 Diabetes Mellitus patients in a highly consanguineous population.DesignCase and control study.SettingThe survey was carried out at the Hamad General Hospital and Primary Health Care (PHC) centers in the State of Qatar.SubjectsThe study was conducted from November 2012 to June 2014 among subjects above 30 years of age. Of the 2224 registered with diagnosed diabetes and free diseases attending Hamad General Hospital and PHC centers agreed and gave their consent to study.MethodsQuestionnaire included socio-demographic variables, body mass index (BMI), consanguinity, lifestyle habits, family history of diabetes, blood pressure and development of diabetes complications such as retinopathy, nephropathy, and neuropathy were collected at regular intervals throughout the follow-up. Univariate and multivariate statistical analysis were performed.ResultsThere were statistically significant difference between patients with diabetic and control in terms of ethnicity (p = 0.012), level of education (p = 0.002), occupation (p < 0.001), monthly income (p < 0.001), BMI(p = 0.024), sport activity (p = 0.018), cigarette smoking (p < 0.001), consanguinity (p = 0.029) and family history of Diabetes Mellitus (p < 0.001) and co-morbidity hypertension (p = 0.041). Further, the biochemistry values in the studied subjects with T2DM compared to healthy controls and the study revealed that serum Vitamin D, BMI, fasting glucose level, calcium, HbA1c, total cholesterol HDL, LDL, bilirubin, triglycerides, uric acid and blood pressure systolic and diastolic were higher in T2DM compared to their counterparts. Multivariate logistic regression showed that vitamin D deficiency ng/mL, Family History of T2DM, BMI (kg/m²) hypertension, consanguinity, income, mother occupation, ethnicity, educational level and Lack of physical exercise variables were significant predictors of diabetes. In the group of Diabetes Mellitus Type 2 patients, 39.3% as opposed to 51.2% in the control group had vitamin D deficiency, 25(OH) D3 levels ≤ 10 ng/ml (p < 0.001). In the group of Diabetes Mellitus Type 2 patients, 34.6% as opposed to 37.9% in the control group had vitamin D insufficiency, 25(OH)D3 levels <20 ng/ml (p < 0.001). In the group of Diabetes Mellitus Type 2 patients, 22.8% as opposed to 14.2% in the control group had vitamin D sufficiency, 25(OH)D3 levels >30 10 ng/ml (p < 0.001).ConclusionVitamin D, family history of diabetes, consanguinity marriages’ and hereditary gene-environment interactions and physical exercise may also contribute to the current diabetes epidemic in Qatari’s Arab populations.     

Parental brevity linked to cardiometabolic risk in diabetic descendants

BackgroundNon-diabetic offspring from long-lived parents benefit from lowered CV risk. No study investigated the effects of parental lifespan on their progeny when offspring have T2DM. This study assessed CV and metabolic features of T2DM offspring according to parental lifespan.Patients & Methods558 T2DM patients were questioned on parental longevity (paternal and/or maternal lifespan ≥ 80 years); mean age 66 (11) years; male:female 66:34; divided into 6 groups: long-lived father [LLF] (n = 143); short-lived father [SLF] (n = 262); long-lived mother [LLM] (n = 229); short-lived mother [SLM] (n = 176); long-lived father and long-lived mother [LLF & LLM] (n = 82); and short-lived father and/or short-lived mother [SLF &/or SLM] (n = 323).ResultsAge was similar in [LLF & LLM] and [SLF &/or SLM]. Diabetes duration was longer in [SLF &/or SLM] (p 0.0073). Body composition, hypertension, hepatic steatosis and metabolic syndrome (MetS) were similar in both groups, [SLF &/or SLM] having a higher MetS score: 3.79 (1.12) vs. 3.48 (1.12) (p 0.0257). Fasting insulinemia was higher in [SLF &/or SLM] (p 0.0001), who were more insulin resistant (+ 10%: p 0.0440). HbA_1c was higher (+ 0.36%) in [SLF &/or SLM] (p 0.0138). LDL-C; non-HDL-C; and apoB100 were similar in both groups, whereas HDL-C and apoA-I were higher in [LLF & LLM] (p 0.0233 and p 0.0179). Prevalence and severity of atherogenic dyslipidemia were raised in [SLF &/or SLM], by 53% (prevalence) and 13% (log[TG]/HDL-C) (p 0.0172 and p 0.0067).ConclusionBilateral reductions in parental longevity are linked to unfavorable cardiometabolic phenotype in T2DM descendants, with worsened insulin resistance and atherogenic dyslipidemia among 1st-degree offspring.     

IRS1 gene variants,dysglycaemic metabolic changes and type-2 diabetes risk

Background and aimsA recent genome-wide association study identified rs2943641C > T, 500 kb from the insulin receptor substrate-1 gene (IRS1), as a type-2 diabetes (T2D) susceptibility locus. We aimed to replicate this association by meta-analysis and examine whether common variants within IRS1, present on the HumanCVD BeadChip, were associated with T2D risk.Methods and resultsWe genotyped rs2943641 in 2389 prevalent or incident T2D patients and 6494 controls from two prospective and three case studies based in UK and in the European Atherosclerosis Research Study-II (EARSII; n = 714). Thirty-three IRS1 variants had been genotyped in the prospective Whitehall-II study (n = 4752) using the HumanCVD BeadChip. In a fixed-effects meta-analysis of the UK study cohorts rs2943641T allele was associated with 6% lower risk of T2D (p = 0.18), with T-allele carriers having an odds ratio (OR) of 0.89 (95% confidence interval [CI]: 0.80–1.00, p = 0.056) compared to CC subjects. The T-allele was also associated with lower fasting insulin and homeostasis model assessment index of insulin resistance in Whitehall-II and with lower post-load insulin after an oral glucose tolerance test in EARSII (all p < 0.05). None of the IRS1 variants on the chip showed linkage disequilibrium with rs2943641. In silico analysis with follow-up genotyping (total n = 9313) identified that the rare allele of the IRS1 promoter variant rs6725556A > G showed association with reduced T2D risk (OR per G-allele: 0.82, 95%CI: 0.69–0.96, p = 0.015).ConclusionsWe confirm the association of rs2943641T with T2D protection. There is a possible independent effect on risk of a putative IRS1 promoter variant.     

Serum Uric Acid concentration is associated with insulin resistance and impaired insulin secretion in adults at risk for Type 2 Diabetes

AimsInsulin resistance (IR) predisposes to type 2 diabetes mellitus (T2DM). Although previous studies have associated serum uric acid concentration with IR in T2DM, its association with impaired insulin secretion and beta-cell dysfunction in subjects at risk for developing T2DM remains uncertain. Thus, we aimed to analyze the association of serum uric acid concentration with IR using surrogate insulin resistance/secretion and beta-cell function indices in subjects at risk for developing T2DM.MethodsThis is a cross-sectional study that included 354 subjects who underwent an oral glucose tolerance test who had at least two risk factors for T2DM without any chronic disease.ResultsParticipants were 51 ± 8 years old, 72.2% were women, had a mean body mass index of 29.9 ± 6.5 kg/m² and mean serum uric acid concentration of 5.7 ± 1.3 mg/dL. HOMA-IR, first-phase insulin secretion (S1Ph_OGTT), second-phase insulin secretion (S2Ph_OGTT), Matsuda and disposition indices were significantly correlated with serum uric acid concentrations (r = 0.239, r = 0.225, r = 0.201, r = ?0.287, r = ?0.208; respectively). After multiple linear regression analysis, serum uric acid concentration was independently associated with HOMA-IR (β = 0.283), HOMA-B (β = 0.185), S1Ph_OGTT (β = 0.203), S2Ph_OGTT (β = 0.186), and Matsuda Index (β = ?0.322). A serum uric acid concentration of 5.5 mg/dL had the best sensitivity/sensibility to identify subjects with IR (HOMA-IR ≥2.5).ConclusionsSerum uric acid concentration is significantly associated with IR and impaired insulin secretion, but not with beta-cell dysfunction, in subjects at risk for developing T2DM.     

Insulin resistance,but not insulin response,during oral glucose tolerance test (OGTT) is associated to worse histological outcome in obese NAFLD

Background and aimObese subjects are at high risk of nonalcoholic fatty liver disease (NAFLD) and diabetes (T2D) due to insulin resistance (IR). Since high glucose levels are as toxic as lipids for hepatic metabolism, we hypothesize that altered response to oral glucose tolerance test (OGTT) is associated to more severe NAFLD with significant/advanced liver damage.Methods and resultsWe studied 90 subjects with morbid obesity (73F/17M, BMI = 43.2 ± 5,9 kg/m²) undergoing bariatric surgery and intraoperative liver biopsy, and measured HbA1c, HOMA-IR (fasting Glucose x Insulin/22.5), OGTT glucose and insulin profile, and calculated OGIS (muscle insulin sensitivity), hepatic-IR (glucose [AUC_0-30] x insulin [AUC_0-30]) during OGTT, insulin response as (insulin [dAUC_0-120]/glucose [dAUC_0-120] or Insulinogenic Index (IGI = (I₃₀–I₀)/(G₃₀-G₀)). Patients were divided in 3 groups according to liver biopsy: A (no-NAFLD, 23%), B (simple steatosis (SS), 53%) and C (NASH, 24%) with similar age, gender and BMI. Diabetes was 0% in no-NAFLD, 13% in SS, 35% in NASH. During OGTT, OGIS decreased from A to C (422 vs 360 vs 338, p < 0.01). Increased insulin concentrations, HbA1c, HOMA-IR and OGIS, not Hep-IR, were strongly associated to hepatic steatosis (p = 0.03, p = 0.0001 and p = 0.01 respectively). Hepatic fibrosis stage was mild as most of the patients had fibrosis grade-1 (69% vs. 8% no fibrosis) and associated to fasting insulin, HbA1c and HOMA-IR. dAUC-I/dAUC-G was similar in the 3 groups, while only AUC-I was strongly associated to steatosis (r = 0.35, p = 0.005), but not to fibrosis.ConclusionsIn morbid obesity indexes of IR, and not of insulin response, are markers of histological severity of liver disease.     

Evolution of subcutaneous adipose tissue fibrosis after bariatric surgery

AimObesity is associated with the development of metabolic complications such as insulin resistance (IR). The mechanisms leading to IR remain unclear. This study aimed to investigate the relationship between adipose tissue fibrosis and IR in obese patients before and after bariatric surgery.MethodsThirty-five obese patients awaiting bariatric surgery (12 with type 2 diabetes) were included in the study. Non-diabetic patients were classified as either insulin-sensitive (n = 11) or insulin-resistant (n = 12), based on the Matsuda insulin sensitivity index (ISI_Matsuda). Homoeostasis model assessment (HOMA-IR) was used for longitudinal evaluation of insulin resistance. Fibrosis was quantified by Masson's trichrome staining on microscopy, and mRNA levels of fibrosis-related genes were examined in subcutaneous (SAT) and visceral adipose tissue (VAT) biopsies collected during and 6 months after bariatric surgery (SAT only).ResultsDespite their similar age, body mass index and fat mass, SAT fibrosis was significantly higher in diabetic vs insulin-sensitive patients (P < 0.05), and associated with IR as assessed by both ISI_Matsuda (r = −0.417, P = 0.038) and HOMA-IR (r = 0.464, P = 0.007) at baseline, whereas VAT fibrosis was not. Six months after surgery and significant weight loss, fibrosis levels remained unchanged in SAT, although IR was significantly reduced in all groups (P < 0.0001). No correlation was found between SAT fibrosis and IR after surgery.ConclusionOverall, these results show a significant but, most likely, transient association between SAT fibrosis and IR in obese humans.     

Serum visfatin levels are positively correlated with dietary carbohydrate and polyunsaturated fatty acid intakes in type 2 diabetes mellitus patients

AimsTo investigate the relationship between dietary intake and biochemical parameters and anthropometric measurements and serum visfatin concentrations.Study designA case-control study.MethodsThe study was carried out in 30 type 2 diabetes mellitus (T2DM) and 30 sex, age and body mass index (BMI) matches healthy control subjects. Biochemical parameters (glycemic and lipid profile, insulin resistance), anthropometric measurements (weight and bioimpedance) and dietary intake evaluation were obtained. Visfatin was assayed with ELISA method.ResultsThe mean BMI of the case group was 31.36 ± 4.37 kg/m² and 29.80 ± 3.53 kg/m² in the control group (p = 0.134). The results revealed a significant increase in the weight, waist circumference, waist/hip ratio, visceral fat ratio, fasting glucose level, HbA1c and fasting insulin as well as in insulin resistance (HOMA-IR) among T2DM patients when compared with controls (p < 0.05). Serum visfatin levels were higher in the subjects with T2DM than healthy control subjects (p < 0.05). There was no significant correlation between visfatin levels and biochemical parameters and anthropometric measurements in patients with T2DM. Serum visfatin level was positively correlated with carbohydrate (CHO) and polyunsaturated fatty acid (PUFA) in T2DM patients (r = 0.406, p = 0.026; r = 0.404, p = 0.027, respectively).ConclusionT2DM patients compares with healthy control group increased serum visfatin levels. PUFA and CHO intake was found to be positively associated with visfatin levels.     

Insulin-induced glucose control improves HDL cholesterol levels but not reverse cholesterol transport in type 2 diabetic patients

Type 2 diabetes (T2D) is characterized by low HDL cholesterol (HDL-C) and HDL dysfunction. We herein tested whether lowering HbA1c affects HDL-C and reverse cholesterol transport (RCT). Forty-two uncontrolled T2D patients initiating basal insulin were included. HbA1c, HDL-C and RCT were assessed at baseline and after 6 months. At baseline, HDL-C and RCT were directly correlated (r = 0.50; p < 0.001). After 6 months of insulin therapy, HbA1c dropped from 8.8 ± 0.16% to 7.1 ± 0.1%, while average HDL-C and RCT did not change. Follow-up HDL-C and RCT were still correlated (r = 0.31; p = 0.033) and ΔHDL-C correlated with ΔRCT (r = 0.32; p = 0.029). ΔHbA1c correlated with ΔHDL-C (r = 0.43, p = 0.001), but not with ΔRCT. In patients with ΔHbA1c above the median value (1.3%), HDL-C (but not RCT) increased significantly. In conclusion, glucose control correlates with increased HDL-C, but not with improved RCT. Thus, persistent HDL dysfunction despite improved HbA1c and HDL-C can contribute to residual cardiovascular risk in T2D.     

Association between insulin resistance and incidence of carotid atherosclerotic plaque: A cohort study

Background and aimsThere is limited evidence on the association between insulin resistance (IR) and carotid plaque was reported in prospective study. We aimed to exploit the relationship between IR and carotid plaque in a prospective cohort study.Methods and resultsThe study was performed in a functional community cohort in urban Beijing. In 2015, a total of 7061 individuals without intima-media thickness (IMT) thickening and carotid artery plaque were recruited and followed up until 2019. Restricted cubic spline was conducted to exploit the dose–response relationship between carotid plaque and baseline HOMA-IR or TyG index as continuous variables. Logistic regression was used to analyze the associations between carotid plaque and HOMA-IR or TyG index. During the average 4 years follow-up, 589 subjects developed carotid plaque. Both HOMA-IR and TyG index showed significant linear dose–response relationship on carotid plaque (p < 0.001). The RRs (95%CI) for subjects with baseline HOMA-IR in quartile 2, quartile 3 and quartile 4 were 1.52 (1.14–2.04), 1.86 (1.40–2.46), and 2.55 (1.94–3.35) compared to quartile 1, respectively. Compared to the first quartile of TyG, the RRs (95%CI) for subjects in quartile 2, quartile 3 and quartile 4 were 1.43 (1.08–1.90), 1.59 (1.20–2.12), and 1.69 (1.26–2.25), respectively. In total population, the predictive ability of HOMA-IR for carotid plaque was significantly better than that of TyG index (p = 0.025).ConclusionIR is an independent risk factor of carotid plaque. Both HOMA-IR and TyG has significant predictive ability for carotid plaque.     

Relationships between changes in leptin and insulin resistance levels in obese individuals following weight loss

Obesity can augment insulin resistance (IR), leading to increased risk of diabetes and heart disease. Leptin, ghrelin, and various fatty acids present in the cell membrane may modulate IR. In this study, we aimed to investigate the impact of weight loss on IR, serum leptin/ghrelin levels, and erythrocyte fatty acids, and studied the associations between changes in these variables. A total of 35 obese (body mass index ≥ 27) adults participated in a weight loss program for 3 months. IR was assessed using homeostasis model assessment for insulin resistance (HOMA-IR). The obese participants had a mean weight loss of 5.6 ± 3.8 kg followed by a 16.7% and 23.3% reduction in HOMA-IR and leptin (p < 0.001) levels, and an 11.3% increase in ghrelin levels (p = 0.005). The level of erythrocyte saturates decreased by 2.8%, while the level of n–3 polyunsaturates increased by 16.8% (all p < 0.05). The changes in leptin levels (?5.63 vs. ?1.57 ng/mL) were significantly different (p = 0.004) in those with improved IR (changes in HOMA-IR < 0) than those without improvement (changes in HOMA-IR ≥ 0), though there were no differences in the changes of ghrelin (p = 0.120) and erythrocyte fatty acids (all p > 0.05) levels. After adjusting for age, gender, changes in ghrelin, and body fat, we found a significant correlation between decreases in leptin and less risk of no improvement in HOMA-IR levels [odds ratio (OR) = 0.69, p = 0.039]. In conclusion, a moderate weight reduction in obese participants over a short period significantly improved IR. This weight reduction concomitantly decreased serum leptin, increased ghrelin, and elevated some erythrocyte unsaturates. Only leptin correlated independently with IR improvement upon multivariable logistic regression analysis, which indicates that leptin may play a role in the modulation of IR following weight loss.     

Is HOMA-IR a potential screening test for non-alcoholic fatty liver disease in adults with type 2 diabetes?

BackgroundNon-alcoholic fatty liver disease (NAFLD) is the commonest hepatic disease in many parts of the World, with particularly high prevalence in patients with type 2 diabetes (T2DM). However, a good screening test for NAFLD in T2DM has not been established. Insulin resistance (IR) has been associated with NAFLD, and homeostatic model assessment of insulin resistance (HOMA-IR), a good proxy for IR, may represent an affordable predictive test which could be easily applied in routine clinical practice. We aimed to evaluate the diagnostic accuracy of HOMA-IR for NAFLD in T2DM and sought to estimate an optimal cut-off value for discriminating NAFLD from non-NAFLD cases.MethodsWe conducted a retrospective analysis of 56 well-controlled patients with T2DM (HbAc1 < 7%, on oral anti-diabetic and/or glucagon-like peptide-1 agonist treatment), who had at least one glucose and insulin level determined, and at least one hepatic imaging test (ultrasonography or computed tomography scanning).ResultsThe prevalence of NAFLD was 73.2% (95% CI: 59.7–84.2) in our population. An association between HOMA-IR and NAFLD was found (OR 1.5; 95% CI: 1.03–2.1; p = 0.033), independently of transaminases, fat percentage, BMI and triglyceride levels. The AUROC curve of HOMA-IR for identifying NAFLD was 80.7% (95% CI: 68.9–92.5). A value of HOMA-IR of 4.5 was estimated to be an optimal threshold for discriminating NAFLD from non-NAFLD cases.ConclusionHOMA-IR is independently associated with the presence of NAFLD in adults with T2DM, and might potentially be applied in clinical practice as a screen for this condition.     

Diabetes-specific variables associated with quality of life changes in young diabetic people: The type 1 diabetes Registry of Turin (Italy)

Background and aimsType 1 diabetes (T1DM) affects young people during the most active years of their life. Our aim was to assess quality of life (QoL) and associated variables in a large cohort of adults with childhood-onset and adult-onset T1DM.MethodsA cohort of adult patients (18 years and older) from the T1DM Registry of Turin, Italy, was recruited. Clinical characteristics and Diabetes QoL (DQOL) questionnaire were assessed by standardized procedures.Results310 adults completed the questionnaire. Age and diabetes duration at assessment (mean ± SD) were 32.8 ± 7.3 years and 17.3 ± 6.3 years, respectively. DQOL and its subscores were in the lower quartiles of their distributions, indicating a good level of QoL. However, scores were significantly higher in females than in males, particularly for the subscale of diabetes-related worries. In multivariate analysis, lower QoL was independently associated with female sex (β = 1.07, 95% CI 1.03–1.11, p = 0.003), higher age at onset (β = 1.03, 1.00–1.05, p = 0.009), lower schooling (β = 1.05, 1.00–1.09, p = 0.02), higher fasting plasma glucose (β = 1.03, 1.01–1.05, p = 0.008), daily SMBG >4 (β = 1.06, 1.01–1.10, p = 0.01), severe hypoglycemia over the last year (β = 1.06, 1.01–1.11, p = 0.02), lower numbers of diabetologic visits (β = 1.07, 1.01–1.13, p = 0.02) and hypertension (β = 1.06, 1.02–1.10, p = 0.005). Autonomic neuropathy was associated with diabetes impact. Female sex (β = 4.36, 2.43–7.83) and daily SMBG >4 (β = 3.77, 1.72–8.30) were independently associated with worst level and CSII with better level (β = 0.22, 0.07–0.68) of diabetes-related worries.ConclusionsThe impact of T1DM on QoL may depend on demographic, metabolic control-related variables, presence of complications and insulin delivery modality.     

Independent association of vitamin D and insulin resistance in obstructive sleep apnea

BackgroundVitamin D insufficiency and/or high levels of parathyroid hormone (PTH) seem to be associated with abnormal glucose metabolism, which is frequent in obstructive sleep apnea (OSA). The purpose of this study was to investigate vitamin D and PTH concentrations in OSA, and to explore potential links between vitamin D, PTH and insulin resistance (IR).MethodsA total of 112 subjects with suspected OSA were recruited consecutively, and evaluated by polysomnography (PSG) to determine the number of apnea and hypopnea episodes per hour of sleep (apnea/hypopnea index: AHI). OSA was diagnosed for AHI ≥ 5. Average (APO2) and minimum pulse oxygen saturation (MPO2) were assessed during PSG as indices of nocturnal hypoxemia. After overnight fasting, a standard 75 g oral glucose tolerance test was performed. Serum 25-hydroxyvitamin D, PTH, fasting glucose and fasting insulin were also measured. Homeostasis model assessment (HOMA) was used to evaluate IR: HOMA-IR = fasting plasma insulin × fasting plasma glucose/22.5, with “insulin resistance” defined as HOMA-IR > 2.7.ResultsPatients were classified into 4 groups according to AHI: control group (AHI < 5, n = 8), mild OSA (5 ≤ AHI < 15, n = 18), moderate OSA (15 ≤ AHI < 30, n = 33), and severe OSA (AHI ≥ 30, n = 53). They were also classified, according to HOMA-IR, as insulin-resistant (HOMA-IR > 2.7, n = 59) or non-insulin-resistant (HOMA-IR ≤ 2.7, n = 45). There were no significant differences in vitamin D or PTH levels between AHI groups. HOMA-IR was significantly higher in severe OSA than in controls (P = 0.019). Vitamin D concentration correlated negatively with AHI (r = ?0.242, P = 0.01) and with HOMA-IR (r = ?0.338, P < 0.001). PTH concentration correlated negatively with vitamin D concentration (P < 0.001), but not with AHI or HOMA-IR. HOMA-IR correlated positively with AHI (r = 0.368, P < 0.001) and negatively with MPO2 (r = ?0.414, P < 0.001). Finally, stepwise linear multivariate regression showed that vitamin D concentration (β = ?0.209, P = 0.014) and MPO2 (β = ?0.221, P = 0.011) were independently associated with HOMA-IR.ConclusionSubjects with severe OSA may have a low vitamin D level associated with increased risk of IR. Vitamin D was independently associated with IR in OSA. Vitamin D insufficiency may play a role in the pathogenesis of IR in OSA.