Homeostasis Model Assessment Of Insulin Resistance Research Articles

Comparative Effects of Moderate Intensity Continuous Training and High Intensity Interval Training on Serum Levels of Myonectin in Rats

Background: Myonectin (CTRP15), a recently identified myokine, plays a crucial role in regulating glucose metabolism. Objectives: This study aimed to compare the effects of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) on serum myonectin levels, using matched training volumes for both interventions. Methods: Twenty-four male Wistar rats, aged 18 to 20 weeks, were randomly assigned to three groups of eight: Control, MICT, and HIIT. The training groups participated in HIIT and MICT programs (three days per week) on a treadmill for eight weeks. Measurements included serum glucose, insulin, myonectin, and the homeostasis model assessment of insulin resistance (HOMA-IR). Additionally, the weight of the Flexor hallucis longus (FHL), gastrocnemius muscles, and epididymal and retroperitoneal fat pads was recorded. Results: Both HIIT and MICT significantly reduced weight gain and fat mass (epididymal and retroperitoneal) compared to the control group (P < 0.05). Eight weeks of HIIT significantly decreased serum insulin levels and HOMA-IR compared to both the control and MICT groups (P < 0.05). No significant differences in serum myonectin levels were observed between the groups. Conclusions: This study suggests that HIIT is more effective than MICT in improving metabolic status in rats, though it does not significantly affect serum myonectin levels.

Role of Serum Magnesium on Insulin Resistance in Overweight and Obese Children.

Background Childhood obesity has become a global epidemic, with projections indicating it could affect 25% of children under 16 by 2050. This rise poses significant health risks, including early onset of type 2 diabetes and cardiovascular diseases. Recent research has shown a correlation between insulin action and magnesium levels, highlighting the link between low serum magnesium levels and obesity. This study aimed to investigate the relationship between serum magnesium levels and obesity in children aged 5-16 years, to compare overweight and obese adolescents with age- and gender-matched controls, and to determine the association between insulin resistance and decreased serum magnesium levels. Methodology At a tertiary hospital, this 1.5-year cross-sectional comparativestudy investigated the relationship between magnesium levels in the blood and insulin resistance in children aged 5-16. Cases met the 2015 revised Indian Academy of Pediatrics (IAP) growth charts for overweight or obesity in comparison to age-matched healthy controls. Exclusions included secondary causes of obesity and medical complications affecting magnesium. Assessments involved clinical history, examination, and fasting blood tests for insulin resistance indices. Results Compared to the controls, overweight children showed that mean serum magnesium levels are lower (1.03 mEq/l vs. 1.85 mEq/l, p<0.001); they were also reflected in higher anthropometric measures, which include body mass index (BMI) and body fat percentage. Cases had significantly higher metabolic markers like fasting insulin, Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) index, and lipid profiles, whereas systolic blood pressure although showing recognized differences did not significantly differ. Conclusion The study underscored the importance of detecting magnesium levels on insulin resistance in overweight and obese children.

Genistein mitigates diet-induced obesity and metabolic dysfunctions in gonadectomized mice with some sex-differential effects.

Obesity is associated with insulin resistance (IR) and metabolic dysfunction-associated steatotic liver disease (MASLD). Genistein, an isoflavone, is a promising natural compound for preventing and treating obesity and metabolic dysfunctions. We aimed to investigate the sex-specific protective effects of genistein on obesity, IR, and MASLD in a murine model of sex hormone deprivation with diet-induced obesity (DIO), mimicking postmenopausal women or aging men with metabolic syndrome. Gonadectomized and sham-operated C57BL/6NJcl mice were fed a high-fat high-sucrose diet for 4 weeks to induce obesity (7 mice per group). In gonadectomized mice, genistein (16 mg/kg/day) or vehicle (7.5% dimethyl sulfoxide) was orally administered for 45 days. We assessed glucose homeostasis parameters, hepatic histopathology, and hepatic gene expression to investigate the effects of gonadectomy and genistein treatment. Gonadectomy exacerbated adiposity in both sexes. Ovariectomy diminished the protective effects of female gonadal hormones on the homeostatic model assessment for insulin resistance (HOMA-IR), serum alanine transaminase levels, hepatic steatosis score, and the expression of hepatic genes associated with MASLD progression and IR, such as Fasn, Srebf1, Saa1, Cd36, Col1a1, Pck1, and Ppargc1a. Genistein treatment in gonadectomized mice significantly reduced body weight gain and the hepatic steatosis score in both sexes. However, genistein treatment significantly attenuated HOMA-IR and the expression of the hepatic genes only in female mice. Genistein treatment mitigates DIO-related MASLD in both male and female gonadectomized mice. Regarding hepatic gene expression associated with MASLD and IR, the beneficial effect of genistein was significantly evident only in female mice. This study suggests a potential alternative application of genistein in individuals with obesity and sex hormone deprivation, yet pending clinical trials.

The effect of vitamin D supplementation on markers of insulin resistance in women with polycystic ovarian syndrome: a systematic review.

Insulin resistance (IR) is a common pathology in women with polycystic ovarian syndrome (PCOS) involved in increased rates of cardiometabolic disease such as diabetes and cardiovascular disease. Low serum vitamin D is often associated with insulin resistance but there is no consensus on whether vitamin D supplementation can ameliorate markers of IR in PCOS. We assessed evidence on the effects of vitamin D supplementation (≥ 1000 IU/day), without the use of additional supplements or other pharmacological treatments known to affect IR, on markers of IR and glycemic control in women with PCOS. A systematic search was conducted using PubMed, Medline and Web of Science databases from January 2000 up to November 2023. Randomized controlled trials that assessed the effects of vitamin D supplementation in women with PCOS, on fasting glucose, fasting insulin, glycated haemoglobin (HbA1c) or homeostatic model assessment for insulin resistance (HOMA-IR) were included. 9 studies were identified. Study populations ranged from 28 to 180 participants, with mean ages ranging from 22 to 30 years. Daily vitamin D doses ranged from 1714-12,000 IU. Of the included studies, 3 reported statistically significant reductions in fasting glucose, 2 reported reductions in fasting insulin, 2 reported reductions in HOMA-IR, none reported reductions in HbA1c and 5 reported no differences in any of the relevant outcomes. In conclusion, in RCTs of vitamin D supplementation in women with PCOS, the majority of studies do not report statistically significant improvements in fasting glucose, fasting insulin, HbA1c or HOMA-IR. However, as a minority of studies report some statistically significant results, further investigation may be warranted. PROSPERO ID: CRD42023486144.

Using anthropometric parameters to predict insulin resistance among patients without diabetes mellitus

Anthropometric parameters are widely used in the clinical assessment of hypertension, type 2 diabetes, and cardiovascular disease. However, few studies have compared the association between different anthropometric parameters and insulin resistance (IR). This study was aimed at investigating the relationship between 6 indicators, including body mass index (BMI), calf circumference (CC), arm circumference (AC), thigh circumference (TC), waist circumference (WC), waist-height ratio (WHtR), and IR. Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) was used to measure IR. Weighted linear regression was used to assess the relationship between different parameters and IR. The receiver operating characteristic curve (ROC) was employed to compare the strength of the relationship between different anthropometric parameters and IR. A total of 8069 participants were enrolled in our study, including 4873 without IR and 3196 with IR. The weighted linear regression results showed that BMI, CC, AC, TC and WC were significantly correlated with IR, except WHtR. After adjusting for multiple confounding factors, we found that BMI, AC and WC were significantly positively correlated with IR, while TC was significantly negatively correlated with IR. Logistic regression results showed that a larger TC was associated with a decreased risk of IR. In addition, BMI and WC had similar areas under the curve (AUC: 0.780, 95% CI 0.770–0.790; AUC: 0.774, 95% CI 0.763–0.784, respectively), which were higher than TC and AC (AUC: 0.698, 95% CI 0.687–0.710, AUC: 0.746, 95% CI 0.735–0.757, respectively). To our knowledge, this is the first study to report a negative correlation between TC and IR among patients without diabetes mellitus. Therefore, TC may be a new tool to guide public health and a clinical predictor of IR in non-diabetic patients.

Microbiota-targeted interventions and clinical implications for maternal-offspring health: An umbrella review of systematic reviews and meta-analyses of randomised controlled trials.

Microbes in the human body are the determinants of life-long health and disease. Microbiome acquisition starts in utero and matures during early childhood through breastfeeding. However, maternal gut dysbiosis affects the maternal-offspring microbiome interplay. Lines of evidence on dysbiosis-targeted interventions and their effect on maternal-offspring health and gut microbiome are inconsistent and inconclusive. Therefore, this study summarised studies to identify the most common microbiota-targeted intervention during pregnancy and lactation and to comprehensively evaluate its effects on maternal and offspring health. This umbrella review was conducted by systematically searching databases such as PubMed and the Web of Science from inception to 2 September 2023. The quality was assessed using the Assessment of Multiple Systematic Reviews-2 checklist. The Grading of Recommendations Assessment, Development, and Evaluation was used for grading the strength and certainty of the studies. The overlap of primary studies was quantified by the corrected covered area score. A total of 17 systematic reviews and meta-analyses with 219 randomised controlled trials, 39 113 mothers, and 20 915 infants were included in this study. About 88% of studies had moderate and above certainty of evidence. Probiotics were the most common and effective interventions at reducing gestational diabetes risk (fasting blood glucose with the mean difference (MD) = -2.92, -0.05; I2 = 45, 98.97), fasting serum insulin (MD = -2.3, -2.06; I2 = 45, 77), glycated haemoglobin (Hb A1c) = -0.16; I2 = 0.00)), Homeostatic Model Assessment of insulin resistance (HOMA-IR) (MD = -20.55, -0.16; I2 = 0.00, 72.00), and lipid metabolism (MD = -5.47, 0.98; I2 = 0.00, 90.65). It was also effective in preventing and treating mastitis (risk ratio (RR) = 0.49; I2 = 2.00), relieving anxiety symptoms (MD = -0.99, 0.01; I2 = 0.00, 70.00), depression in lactation (MD = -0.46, -0.22; I2 = 0.00, 74.00) and reducing recto-vaginal bacterial colonisation (odds ratio (OR) = 0.62; I2 = 4.80), and with no adverse events. It also effectively remodelled the infant gut microbiome (MD = 0.89; I2 = 95.01) and prevented infant allergies. However, studies on pregnancy outcomes and preeclampsia incidences are limited. Our findings from high-quality studies identify that probiotics are the most common microbiome interventions during pregnancy and lactation. Probiotics have a strong impact on maternal and offspring health through maintaining gut microbiome homeostasis. However, further studies are needed on the effect of microbiota-targeted interventions on maternal cardiometabolic health, pregnancy, and neonatal outcomes. This umbrella review was registered with PROSPERO, CRD42023437098.

Investigating the efficacy of acupuncture in treating patients with metabolic-associated fatty liver disease: a protocol for a randomised controlled clinical trial

IntroductionAcupuncture is widely used for metabolic-associated fatty liver disease (MAFLD) treatment; however, the clinical efficacy has not been confirmed due to the lack of high-level evidence-based clinical practice. The purpose...

Diabetes and uterine fibroid diagnosis in midlife: Study of Women's Health Across the Nation (SWAN).

Fibroids are non-cancerous uterine tumors potentially associated with cardiovascular risk factors. We examined prospectively associations of glucose, insulin, sex hormone binding globulin (SHBG), and diabetes with incidence of fibroid diagnoses in midlife. Participants in the Study of Women's Health Across the Nation (SWAN) cohort (n=2570) reported fibroid diagnoses at enrollment (1996-1997) and 13 follow-up visits (1996-2013). At all visits, we measured glucose, insulin, and SHBG in fasting blood samples and calculated homeostatic model assessment for insulin resistance (HOMA-IR). Diabetes was defined using glucose levels, self-reported diabetes, or diabetes medication use. We used discrete-time survival models to estimate hazard ratios (HR) and 95% confidence intervals (CI) for associations of time-varying biomarkers and diabetes with incident fibroid diagnoses, adjusted for demographics and healthcare utilization. We also evaluated effect modification by menopausal status. At baseline, 2.7% of participants (n=70) were using diabetes medication. Time-varying glucose, insulin, HOMA-IR, and SHBG were not associated with fibroid diagnosis. However, diabetes was associated with a 28% lower incidence of fibroid diagnosis (adjusted HR: 0.72, 95% CI: 0.44, 1.17), driven by participants using metformin (adjusted HR: 0.49, 95% CI: 0.21, 1.12), though precision was limited. After stratification by menopausal status, higher HOMA-IR and insulin were associated with greater incidence of fibroid diagnosis during premenopause but not perimenopause, while the inverse association between diabetes and fibroids was strongest during perimenopause. The effect of diabetes and biomarkers on fibroids may vary by menopausal status. Fibroid risk may increase with insulin resistance and decrease with diabetes treatment.

A Randomized Trial of the Efficacy of Three Weight Loss Diet Interventions in Overweight/Obese with Polycystic Ovary Syndrome.

Polycystic Ovary Syndrome (PCOS) is a highly prevalent, complex, heterogeneous, polygenic endocrine disorder characterized by metabolic and reproductive dysfunction that affects 8-13% of women of reproductive age worldwide. The pathogenesis of PCOS has not been fully clarified and includes genetics, obesity, and insulin resistance (IR). Oxidative stress (OS) of PCOS is independent of obesity. It can induce IR through post-insulin receptor defects, impair glucose uptake in muscle and adipose tissue, and exacerbate IR by reducing insulin secretion from pancreatic β-cells. To investigate the effects of Calorie Restricted Diet (CRD), High Protein Diet (HPD), and High Protein and High Dietary Fiber Diet (HPD+HDF) on body composition, insulin resistance, and oxidative stress in overweight/obese PCOS patients. A total of 90 overweight/obese patients with PCOS were selected to receive an 8- week medical nutrition weight loss intervention at our First Hospital of Peking University, and we randomly divided them into the CRD group (group A), the HPD group (group B), and the HPD+HDF group (group C), with 30 patients in each group. We measured their body composition, HOMA-IR index, and oxidative stress indicators. The t-test, Mann-Whitney U test, analysis of variance (ANOVA), and Kruskal-Wallis H test were used to compare the efficacy of the three methods. After eight weeks, the body weights of the three groups decreased by 6.32%, 5.70% and 7.24%, respectively, and the Visceral Fat Area (VFA) values decreased by 6.8 cm2, 13.4 cm2 and 23.45 cm2, respectively, especially in group C (p <0.05). The lean body mass (LBM), also known as the Fat-Free Mass (FFM) values of group B and group C after weight loss, were higher than that of group A (p <0.05). After weight loss, the homeostatic model assessment of insulin resistance (HOMA-IR) index and malondialdehyde (MDA) were decreased. Superoxide dismutase (SOD) was increased in all three groups (p <0.05), and the changes in SOD and MDA in group B and group C were more significant (p <0.05). HOMA-IR index positively correlated with body mass index (BMI) (r=0.195; p <0.05); MDA positively correlated with percent of body fat (PBF) (r=0.186; p <0.05) and HOMA-IR index (r=0.422; p <0.01); SOD positively correlated with LMI/FFMI (r=0.195; p <0.05), negatively correlated with HOMA-IR index (r=-0.433; p <0.01). All three diets were effective in reducing the body weight of overweight/obese patients with PCOS by more than 5% within 8 weeks and could improve both insulin resistance and oxidative stress damage. Compared with CRD, HPD and HPD+HDF diets could better retain lean body mass and significantly improve oxidative stress damage.

Relationship between radiation dose and markers of insulin resistance and inflammation in atomic bomb survivors.

In recent studies of childhood cancer survivors, diabetes has been considered a late effect associated with high therapeutic doses of radiation therapy. Our recent study of atomic bomb (A-bomb) survivors also suggested an association between radiation dose and diabetes incidence, with exposure city and age at exposure as radiation dose effect modifiers. Insulin resistance mediated by systemic inflammation and abnormal body composition has been suggested as a possible primary mechanism for the incidence of diabetes after total body irradiation, however, no studies have examined low-to- moderate radiation exposure (<4 Gy) and insulin resistance in A-bomb survivors. To examine the association between radiation dose and markers of inflammation and insulin resistance. This study investigated 3,152 survivors who underwent a health examination between 2008 and 2012 and who were younger than 15 years at exposure. Multivariate linear regression analyses were used to evaluate the radiation effects on levels of markers of inflammation and insulin resistance. Radiation dose was significantly and positively associated with levels of CRP, triglycerides, homeostasis model assessment of β-cell function (HOMA-β), and HOMA of insulin resistance (HOMA-IR) after adjustment for relevant covariates including sex, city, and age at exposure. Adiponectin and HDL cholesterol levels were also associated significantly and negatively with radiation dose. However, city was not a dose modifier of the radiation response on these markers of inflammation and insulin resistance. Insulin resistance might be a possible factor in the radiation related diabetes incidence in the A-bomb survivors.

Selenoprotein-p and insulin resistance in children and adolescents with obesity.

Insulin resistance and obesity present significant challenges in pediatric populations. Selenoprotein P1 (SEPP1) serves as a biomarker for assessing selenium levels in the body. While its association with metabolic syndrome is established in adults, its relevance in children remains underexplored. To ascertain SEPP1 blood levels in children and adolescents diagnosed with obesity and to assess its correlation with insulin resistance and adiposity indices. 170 children participated in this study, including 85 diagnosed with obesity and an equal number of healthy counterparts matched for age and sex. Each participant underwent a comprehensive medical evaluation, encompassing a detailed medical history, clinical examination, and anthropometric measurements like waist circumference and waist-to-height ratio. Furthermore, routine blood tests were conducted, including serum SEPP1, visceral adiposity index (VAI), and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) level. Our findings revealed significantly lower serum SEPP1 levels in children with obesity compared to their healthy peers. Moreover, notable negative correlations were observed between serum SEPP1 levels and body mass index, VAI, and HOMA-IR. The study suggests that SEPP1 could serve as a valuable predictor for insulin resistance among children and adolescents diagnosed with obesity. This highlights the potential utility of SEPP1 in pediatric metabolic health assessment and warrants further investigation.

Glucose metabolism and smaller hippocampal volume in elderly people with normal cognitive function

We investigated associations of glycemic measures, and insulin resistance and secretion measures with hippocampal and subfield volumes. In this cross-sectional study, 7400 community-dwelling participants underwent brain MRI and health checkups between 2016 and 2018. Hemoglobin A1c (HbA1c), glycated albumin (GA), homeostasis model assessment for insulin resistance (HOMA-IR), and HOMA of percent β-cell function (HOMA-β) were evaluated. The associations of each measure with a smaller volume of the hippocampus and twelve hippocampal subfields were investigated. As a result, higher HbA1c or GA and lower HOMA-β levels were significantly associated with smaller volumes in multiple hippocampal subfields. Furthermore, even when we analyzed non-diabetic individuals, substantial associations remained between higher GA or lower HOMA-β levels and smaller volumes of the whole hippocampus or the fimbria. Our findings indicate that postprandial glucose fluctuations, postprandial hyperglycemia, and low insulin secretion have a specific effect on the development of smaller hippocampal volume, suggesting that primary prevention of diabetes and/or sufficient glucose control are important for the prevention of dementia.

The Concentration of Follistatin and Activin A in Serum and Selected Biochemical Parameters in Women with Polycystic Ovary Syndrome: Stratification by Tobacco Smoke Exposure, Insulin Resistance, and Overweight/Obesity.

Background/Objectives: The aim of the study was to investigate the concentrations of follistatin and activin A in the serum of women with polycystic ovary syndrome (PCOS) and to assess their relationship with selected biochemical parameters, specifically stratifying the analysis based on tobacco smoke, insulin resistance, and abnormal weight. Methods: The research was carried out within a cohort of 88 women (60 women with and 28 without PCOS). Results: We observed significant differences (p < 0.05) in follistatin concentrations between women with PCOS stratified by homeostatic model assessment for insulin resistance (HOMA-IR) values. These differences were consistent across both smoking and non-smoking subgroups with PCOS. Similar results were observed when comparing normal-weight women with PCOS to those with overweight or obesity. Additionally, activin A concentrations were significantly increased by higher body mass index (BMI) and HOMA-IR values in non-smoking women with PCOS. Moreover, we identified a negative correlation (r = -0.30; p < 0.023) between cotinine levels and Anti-Müllerian hormone. Among smoking women with PCOS, we noted decreased concentrations of sex hormone-binding globulin and high-density lipoproteins, alongside increased fasting glucose, insulin, HOMA-IR, and free androgen index values. Conclusions: Our findings suggest that activin A and follistatin concentrations are more strongly influenced by disruptions in glucose metabolism and BMI than by tobacco smoke exposure. The observed changes were more pronounced in follistatin than in activin A level.

The 5:2 Diet Affects Markers of Insulin Secretion and Sensitivity in Subjects with and without Type 2 Diabetes-A Non-Randomized Controlled Trial.

This non-randomized controlled trial aimed to compare the effect of the 5:2 diet on insulin levels as a primary outcome and markers of insulin secretion (connecting peptide (C-peptide) and insulin-like growth factor binding protein-1 (IGFBP-1)) and sensitivity (Homeostatic Model Assessment for Insulin Resistance (HOMA-IR)), as well as body composition as secondary outcomes in overweight/obese individuals with and without type 2 diabetes (T2D). Ninety-seven participants (62% women), 35 with T2D and 62 BMI- and waist-matched controls without T2D, followed the 5:2 diet (two days per week of fasting) for six months with a 12-month follow-up. At six months, there was no loss to follow-up in the T2D group, whereas four controls discontinued this study. Overall, 82% attended the 12-month follow-up. After the intervention, insulin levels decreased in the control group and glucose decreased in the T2D group, while C-peptide, HOMA-IR, waist circumference, BMI, trunk, and total fat% decreased in both groups. Furthermore, low IGFBP-1, indicating hyperinsulinemia, improved in the T2D group. The changes in fasting glucose and waist measurement were significantly more improved in the T2D group than in the controls. Persistent positive effects were observed at the 12-month follow-up. The 5:2 diet for six months was feasible and efficient to reduce markers of insulin secretion and resistance and therefore holds promise as management of overweight/obesity in subjects with and without T2D.

The Relationship between Vitamin D, Inflammatory Markers, and Insulin Resistance in Children.

In this study, we investigated 25-hydroxyvitamin D (25(OH)D, vitamin D), inflammatory hematologic ratios such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), monocyte/HDL-C ratio (MHR) and plasma atherogenic index (PAI) and possible relationships with insulin resistance (IR) in children. A total of 210 individuals, including 96 children with IR and 114 children without IR, aged 6-18 years, who were admitted to the Pediatric Endocrinology Outpatient Clinic at Medicine Hospital, Istanbul Atlas University were included in our study. Compared to patients without IR, NLR, PLR, SII, and MHR were significantly higher in patients with IR. Fasting insulin, PAI, homeostasis model assessment of insulin resistance (HOMA-IR), and HOMA-β were significantly higher and quantitative insulin sensitivity check index (QUICKI) was considerably lower in patients with IR compared to those without IR. NLR, SII, and MHR were lower in normal vitamin D groups than the others (p < 0.001). PLR was lower in the group with normal vitamin D levels than the groups with insufficient or deficient levels of vitamin D (D < 21). We found that vitamin D deficiency in childhood is related to increased levels of circulating inflammatory markers (NLR, PLR, MHR, PAI), IR, and decreased insulin sensitivity. According to our results, supplementation of vitamin D may be beneficial in averting IR and enhanced systemic inflammation.

Mediating role of inflammatory biomarkers in the causal effect of body composition on glycaemic traits and type 2 diabetes.

The aim was to investigate the mediating role of inflammatory biomarkers in the causal effect of body composition on glycaemic traits and type 2 diabetes. A retrospective observational study and a Mendelian randomization (MR) study were used. Observational analyses were performed using data from 4717 Chinese children and adolescents aged 6-18 years who underwent dual-energy X-ray absorptiometry for body composition. MR analyses were based on summary statistics from UK Biobank, deCODE2021, Meta-Analysis of Glucose and Insulin-Related Traits Consortium (MAGIC) and other large consortiums. Inflammatory biomarkers included leptin, adiponectin, osteocalcin, fibroblast growth factor 23 (FGF23) and parathyroid hormone (PTH). In a retrospective observational study, increased fat mass had a positive effect on homeostasis model assessment of insulin resistance (HOMA-IR) and homeostasis model assessment of pancreatic beta cell function (HOMA-β) through FGF23, whereas fat-free mass produced the opposite effects. PTH and osteocalcin played significant roles in the association of fat mass and fat-free mass with fasting glucose, fasting insulin and HOMA-IR (all p < 0.05). Mediation MR results indicated that childhood body mass index affected glycaemic traits through leptin and adiponectin. There existed a causal effect of fat-free mass on type 2 diabetes via FGF23 (indirect effect: OR [odds ratio]: 1.14 [95% CI, confidence interval: 1.01-1.28]) and adiponectin (OR: 0.85 [95% CI: 0.77-0.93]). Leptin mediated the causal association of fat mass (indirect effect: β: -0.05 [95% CI: -0.07, -0.02]) and fat-free mass (β: 0.03 [95% CI: 0.01, 0.04]) with fasting glucose. Our findings suggest that different body compositions have differential influences on glycaemic traits and type 2 diabetes through distinct inflammatory biomarkers. The findings may be helpful in tailoring management of body composition based on inflammatory biomarkers with different glycaemic statuses.

Clinical application of cluster analysis in patients with newly diagnosed type 2 diabetes.

Early prevention and treatment of type 2 diabetes mellitus (T2DM) is still a huge challenge for patients and clinicians. Recently, a novel cluster-based diabetes classification was proposed which may offer the possibility to solve this problem. In this study, we report our performance of cluster analysis of individuals newly diagnosed with T2DM, our exploration of each subtype's clinical characteristics and medication treatment, and the comparison carried out concerning the risk for diabetes complications and comorbidities among subtypes by adjusting for influencing factors. We hope to promote the further application of cluster analysis in individuals with early-stage T2DM. In this study, a k-means cluster algorithm was applied based on five indicators, namely, age, body mass index (BMI), glycosylated hemoglobin (HbA1c), homeostasis model assessment-2 insulin resistance (HOMA2-IR), and homeostasis model assessment-2 β-cell function (HOMA2-β), in order to perform the cluster analysis among 567 newly diagnosed participants with T2DM. The clinical characteristics and medication of each subtype were analyzed. The risk for diabetes complications and comorbidities in each subtype was compared by logistic regression analysis. The 567 patients were clustered into four subtypes, as follows: severe insulin-deficient diabetes (SIDD, 24.46%), age-related diabetes (MARD, 30.86%), mild obesity-related diabetes (MOD, 25.57%), and severe insulin-resistant diabetes (SIRD, 20.11%). According to the results of the oral glucose tolerance test (OGTT) and biochemical indices, fasting blood glucose (FBG), 2-hour postprandial blood glucose (2hBG), HbA1c, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and triglyceride-glucose index (TyG) were higher in SIDD and SIRD than in MARD and MOD. MOD had the highest fasting C-peptide (FCP), 2-hour postprandial C-peptide (2hCP), fasting insulin (FINS), 2-hour postprandial insulin (2hINS), serum creatinine (SCr), and uric acid (UA), while SIRD had the highest triglycerides (TGs) and TyG-BMI. Albumin transaminase (ALT) and albumin transaminase (AST) were higher in MOD and SIRD. As concerms medications, compared to the other subtypes, SIDD had a lower rate of metformin use (39.1%) and a higher rate of α-glucosidase inhibitor (AGI, 61.7%) and insulin (74.4%) use. SIRD showed the highest frequency of use of sodium-glucose cotransporter-2 inhibitors (SGLT-2i, 36.0%) and glucagon-like peptide-1 receptor agonists (GLP-1RA, 19.3%). Concerning diabetic complications and comorbidities, the prevalence of diabetic kidney disease (DKD), cardiovascular disease (CVD), non-alcoholic fatty liver disease (NAFLD), dyslipidemia, and hypertension differed significantly among subtypes. Employing logistic regression analysis, after adjusting for unmodifiable (sex and age) and modifiable related influences (e.g., BMI, HbA1c, and smoking), it was found that SIRD had the highest risk of developing DKD (odds ratio, OR = 2.001, 95% confidence interval (CI): 1.125-3.559) and dyslipidemia (OR = 3.550, 95% CI: 1.534-8.215). MOD was more likely to suffer from NAFLD (OR = 3.301, 95%CI: 1.586-6.870). Patients with newly diagnosed T2DM can be successfully clustered into four subtypes with different clinical characteristics, medication treatment, and risks for diabetes-related complications and comorbidities, the cluster-based diabetes classification possibly being beneficial both for prevention of secondary diabetes and for establishment of a theoretical basis for precision medicine.

Effect of irisin on ovarian phosphatidylinositol-3-kinase/protein kinase B signaling pathway and mitogen-activated protein kinase/extracellular signal-regulated kinase pathways of rats with polycystic ovary syndrome.

To investigate the independent effects of irisin on insulin resistance (IR) in ovary of polycystic ovary syndrome (PCOS) and explore possible pathways. We established PCOS medel using Poretsky L's method, then PCOS rats were randomly divided into model group (M) and irisin group (I), and normal rats (N) were used as the control. Then rats in the group I were injected with recombinant irisin. Then the levels of circulating fasting blood glucose (FBG), fasting insulin (FINS), homeostasis model assessment of IR (HOMA-IR) and PI3K/AKT and MAPK/ERK pathways in each group were observed, as well as the effects of irisin on the levels of circulating HOMA-IR and PI3K/AKT and MAPK/ERK pathways in ovary of PCOS rats were evaluated. Compared with normal group, levels of FBG, FINS, and HOMA-IR of model group were significantly increased (p < 0.001, p < 0.001, and p < 0.001, respectively), levels of average optical density by IHC of p-PI3K, PI3K, p-AKT, and AKT (p = 0.015, p = 0.010, p = 0.005, and p = 0.009, respectively) and levels of mRNA concentration of PI3K and AKT (p = 0.001, and p = 0.005, respectively) were decreased, while the levels of average optical density of p-ERK, ERK (p = 0.011, and p = 0.013, respectively) and level of mRNA concentration of ERK (p < 0.001) were increased in ovary. After irisin intervention, compared with model group, levels of FBG, FINS, and HOMA-IR of rats in irisin group were significantly decreased (p = 0.001, p < 0.001, and p < 0.001, respectively), levels of average optical density by IHC of p-PI3K, PI3K, p-AKT, and AKT (p = 0.030, p = 0.024, p = 0.012, and p = 0.025, respectively) and levels of mRNA concentration of PI3K and AKT (p = 0.002, and p = 0.003, respectively) were significantly increased, while the levels of average optical density of p-ERK, ERK (p = 0.004, and p = 0.026, respectively) and level of mRNA concentration of ERK (p = 0.001) were significantly decreased. Our study demonstrated that irisin could not only improve circulating insulin resistance, but may also improve ovarian IR through an increase in the activity of PI3K/AKT signaling and a decrease of MAPK/ERK signaling.

Effect of Vitamin D Supplementation on Glycemic Control in Newly Diagnosed Patients With Type 2 Diabetes Mellitus: A Randomized Controlled Trial.

Vitamin D deficiency is commonly associated with type 2 diabetes and it has been linked to impaired glycemic control in these patients. This study was done to determine if vitamin D supplementation improves glycemic parameters in type 2 diabetes. This randomized controlled trial was done in 140 newly diagnosed adult patients with type 2 diabetes. The participants were randomly divided into two groups where one group received vitamin D (60,000 International Units (IU) of oral vitamin D3 weekly for a duration of three months, followed by 1000 IU twice daily for another three months in vitamin D deficient patients; 1000 IU (25 mcg) twice daily for six months for subjects with sufficient vitamin D level) along with standard anti-diabetic drugs while the other group received standard anti-diabetic drugs only. The effect of vitamin D supplementation was assessed by measuring glycated haemoglobin (HbA1c), fasting blood sugar (FBS), postprandial blood sugar (PPBS), fasting insulin, and insulin resistance as Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) at the baseline and after six months. Vitamin D deficiency was observed in 60% (n=84) of the subjects with the rest 40% (n=56) having sufficient serum vitamin D levels. The baseline mean HbA1c was 8.48 ± 1.46% and 8.21 ± 1.24% in the control and vitamin D group, respectively. After supplementing vitamin D for six months, no significant difference was observed between the two groups in terms of HbA1c (p= 0.263). Similarly, there was no significant change in other parameters like FBS, PPBS, fasting insulin, and insulin resistance (HOMA-IR). A subgroup analysis within the vitamin D group between the vitamin D sufficient and deficient patients also revealed no significant changes in the above parameters. Vitamin D supplementation, within the parameters of this study, did not yield a distinctive advantage in improving glycemic outcomes in individuals with type 2 diabetes.

Association Between Weight-Adjusted Waist Index and Albuminuria in Type 2 Diabetes Mellitus in the Chinese Population.

This study aimed to investigate the relationship between weight-adjusted waist index (WWI) and albuminuria in patients with type 2 diabetes mellitus (T2DM) in the Chinese population. A total of 860 adult patients in the Department of Endocrinology of the Affiliated Hospital of Jiangsu University were retrospectively analyzed from June 2018 to September 2023. Correlations between WWI and albuminuria (albumin-to-creatinine ratio (UACR) ≥ 30 mg/g were defined as albuminuria) were analyzed using the Pearson and Spearman methods. The associations between albuminuria and Age, gender, body mass index (BMI), waist circumference/ hip circumference (WHR), systolic blood pressure(SBP), diastolic blood pressure (DBP), fasting plasma glucose (FPG), 2-hour postprandial plasma glucose (2h PG), fasting plasma insulin (FIns), 2-h postprandial insulin (2hINS), glycosylated hemoglobin (HbA1c), WWI, homeostasis model assessment of insulin resistance (HOMA-IR) were analyzed via binary logistic regression. Compared with the normal albumin group, serum urea nitrogen, serum creatinine, UACR, and WWI levels in the albuminuria group were significantly increased, while estimated glomerular filtration rate (eGFR) levels were significantly decreased (P < 0.05). Correlation analyses revealed that WWI was positively correlated with UACR but negatively correlated with urea nitrogen, serum creatinine, and eGFR (P < 0.05). Binary logistic regression analyses indicated that WWI was an independent risk factor for albuminuria in T2DM patients. Receiver operating characteristic curve results showed that the area under the curve for albuminuria as predicted by WWI was 0.605 [95% CI = (0.563-0.646), P < 0.001]. WWI is independently associated with albuminuria in the Chinese patients with type 2 diabetes and may serve as a simple indicator for albuminuria risk assessment.