Homeostasis Model Assessment Of Insulin Resistance Research Articles

A prospective observational cross-sectional study on the association of non-alcoholic fatty liver disease and insulin resistance in acute ischemic stroke in tertiary care hospital in Central India

Background Non-alcoholic Fatty Liver Disease (NAFLD) and insulin resistance have individually been associated with increased cardiovascular risk, and their potential interplay in the context of Acute Ischemic Stroke remains a subject of investigation. This study aims to elucidate the association between NAFLD, insulin resistance, and Acute Ischemic Stroke, exploring risk factors, etiology, and potential implications for patient management. Methods This prospective observational cross-sectional study will be conducted at Acharya Vinoba Bhave Rural Hospital, enrolling patients aged 40-79 diagnosed with acute ischemic stroke between 2022 and 2025. Diagnostic confirmation will involve brain imaging, and abdominal ultrasonography will assess NAFLD severity. Biochemical parameters will be measured for insulin resistance evaluation, including blood glucose, glycosylated hemoglobin (HbA1c), and fasting insulin levels. The Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) will be calculated. Statistical analyses, including descriptive statistics and bivariate and multivariate analyses, will be applied to explore associations and potential risk factors. Expected Outcome Anticipated findings include insights into the prevalence and severity of NAFLD in Acute Ischemic Stroke patients, the association between insulin resistance and stroke incidence, and potential risk factors contributing to this association. The study provides a foundation for understanding the complex relationship between NAFLD, insulin resistance, and Acute Ischemic Stroke, offering valuable implications for risk stratification and patient management in clinical practice. Identifying modifiable risk factors may guide targeted interventions, contributing to improved outcomes in this patient population.

A Nonlinear Relation between Body Mass Index and Long-Term Poststroke Functional Outcome-The Importance of Insulin Resistance, Inflammation, and Insulin-like Growth Factor-Binding Protein-1.

Both high serum insulin-like growth factor-binding protein-1 (s-IGFBP-1) and insulin resistance (IR) are associated with poor functional outcome poststroke, whereas overweight body mass index (BMI; 25-30) is related to fewer deaths and favorable functional outcome in a phenomenon labeled "the obesity paradox". Furthermore, IGFBP-1 is inversely related to BMI, in contrast to the linear relation between IR and BMI. Here, we investigated s-IGFBP-1 and IR concerning BMI and 7-year poststroke functional outcome. We included 451 stroke patients from the Sahlgrenska Study on Ischemic Stroke (SAHLSIS) with baseline measurements of s-IGFBP1, homeostasis model assessment of IR (HOMA-IR), BMI (categories: normal-weight (8.5-25), overweight (25-30), and obesity (>30)), and high-sensitivity C-reactive protein (hs-CRP) as a measure of general inflammation. Associations with poor functional outcome (modified Rankin scale [mRS] score: 3-6) after 7 years were evaluated using multivariable binary logistic regression, with overweight as reference due to the nonlinear relationship. Both normal-weight (odds-ratio [OR] 2.32, 95% confidence interval [CI] 1.30-4.14) and obese (OR 2.25, 95% CI 1.08-4.71) patients had an increased risk of poor functional outcome, driven by deaths only in the normal-weight. In normal-weight, s-IGFBP-1 modestly attenuated (8.3%) this association. In the obese, the association was instead attenuated by HOMA-IR (22.4%) and hs-CRP (10.4%). Thus, a nonlinear relation between BMI and poor 7-year functional outcome was differently attenuated in the normal-weight and the obese.

Association between vitamin D levels and insulin resistance in patients with type 2 diabetes mellitus

Background: Insulin resistance (IR) is a major contributor to type 2 diabetes mellitus (T2DM) and is associated with various metabolic disorders. Vitamin D deficiency (VDD) has been linked to an increased risk of T2DM, but the relationship between vitamin D status and IR in T2DM patients remains unclear. This study explores this association in a male population with T2DM in Baghdad, Iraq.Methods: A case-control study was conducted on 190 male participants: 40 healthy controls and 150 patients categorized into different groups; 40 diabetic patients, 55 with coronary artery disease (CAD) and T2DM (CAD+DM), and 55 with only CAD. Physicians diagnosed them, and they were evaluated by physical and full medical history. All the sample set parameters were measured in the fasting state for each group. The biochemical tests included body mass index (BMI), vitamin D levels, insulin levels, fasting tests glucose (FBG), and HbA1c were measured. Insulin resistance was calculated using the HOMA-IR model.Results: Vitamin D levels were significantly lower in all diabetic groups (DM, CAD+DM) compared to the control group (p<0.001). All diabetic patients had insulin resistance. BMI was significantly higher in the CAD and CAD+DM groups compared to controls (p<0.00001, p<0.004). FBG, HbA1c, insulin levels, and HOMA-IR were all significantly higher in diabetic patients compared to controls (p<0.001 for all). Furthermore, increased HbA1c, fasting insulin, and homeostatic model assessment for insulin resistance (HOMA-IR) were associated with CAD progression in T2DM patients (p < 0.001).Conclusion: This study suggests that vitamin D deficiency may contribute to insulin resistance in male T2DM patients in Baghdad, Iraq. Maintaining optimal vitamin D levels may be beneficial in diabetes management in this population. Incorporating vitamin D screening into routine check-ups for T2DM patients could aid in early detection and prevention of insulin resistance-associated complications.Keywords: Diabetes mellitus; Insulin resistance; Vitamin D; Coronary artery disease

Aqueous Extract of Terminalia bellirica Fruits Improves Insulin Sensitivity, Controls Hyperglycaemia and Improves SIRT1 Expression in High-fat Diet and Streptozotocin-induced Type 2 Diabetes in Rats

Background: Plants from the genus “Terminalia” are well known for their various pharmacological and medicinal properties. Terminalia bellirica is considered a vital medicinal plant from the genus Terminalia. It has been reported for its astringent, antipyretic, and purgative effects. It is also used to treat dyspepsia, tropical pulmonary eosinophilia, allergic eruptions, bronchitis, upper respiratory tract infections, and leprosy. The present research study aimed to investigate the antidiabetic activity of T. bellirica in an experimental model of type 2 diabetes in experimental rats. Materials and Methods: In rats, type 2 diabetes was induced by the alteration in the diet by administration of a high-fat diet for 15 days, followed by the administration of streptozotocin (35 mg/kg, i.p.). The experimental animals were given 500 and 1,000 mg/kg of T. bellirica aqueous fruit extract for six weeks. Liver enzymes and lipid parameters, homeostatic model assessment–insulin resistance, insulin sensitivity index, glycohemoglobin, and oral glucose tolerance tests were performed at the end of the study. Histopathology and immunohistochemical analysis for the SIRT1 expression of pancreatic tissue were also performed. Results: The selected doses of the aqueous extract of T. bellirica (500 and 1,000 mg/kg) significantly reduced blood glucose ( p < .05). The 1,000 mg/kg dose of T. bellirica notably decreased glucose tolerance ( p < .001) in experimental animals. A high dose of T. bellirica significantly reduced resistance ( p < .001). The lipid profile was improved significantly ( p < .01) at both the selected dose levels. Glycohemoglobin concentration was significantly reduced in experimental animals ( p < .001) at both dose levels. The extract treatment increased the expression of SIRT1 in the pancreas. Conclusion: The results of the present study indicate that the extract has significant effects on the management of type 2 diabetes.

The effect of adipose-derived mesenchymal stem cell transplantation on ovarian mitochondrial dysfunction in letrozole-induced polycystic ovary syndrome in rats: the role of PI3K-AKT signaling pathway

ObjectiveThe present study aimed to elucidate how mesenchymal stem cells (MSCs) application could efficiently attenuate pathological changes of letrozole-induced poly cystic ovary syndrome (PCOS) by modulating mitochondrial dynamic via PI3K-AKT pathway.MethodsThirty-two female rats were randomly divided into four experimental groups: Sham, PCOS, PCOS + MSCs, and PCOS + MSCs + LY294002. The Sham group received 0.5% w/v carboxymethyl cellulose (CMC); the PCOS group received letrozole (1 mg/kg, daily) in 0.5% CMC for 21 days. Animals in the PCOS + MSCs group received 1 × 106 MSCs/rat (i.p,) on the 22th day of the study. In the PCOS + MSCs + LY294002 group, rats received LY294002 (PI3K-AKT inhibitor) 40 min before MSC transplantation. Mitochondrial dynamic gene expression, mitochondrial membrane potential (MMP), citrate synthase (CS) activity, oxidative stress, inflammation, ovarian histological parameters, serum hormone levels, homeostatic model assessment for insulin resistance (HOMA-IR), insulin and glucose concentrations, p-PI3K and p-AKT protein levels were evaluated at the end of the experiment.ResultsPCOS rats showed a significant disruption of mitochondrial dynamics and histological changes, lower MMP, CS, ovary super oxide dismutase (SOD) and estrogen level. They also had a notable rise in insulin and glucose concentrations, HOMA-IR, testosterone level, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels, ovarian malondialdehyde (MDA) content as well as a notable decrease in p-PI3K and p-AKT protein levels compared to the Sham group. In the PCOS + MSCs group, the transplantation of MSCs could improve the above parameters. Administration of LY294002 (PI3K-AKT pathway inhibitor) deteriorated mitochondrial dynamic markers, oxidative stress status, inflammation markers, hormonal levels, glucose, and insulin levels and follicular development compared to the PCOS + MSCs group.ConclusionsThis study demonstrated that the protective effects of MSC transplantation in regulating mitochondrial dynamics, promoting mitochondrial biogenesis, competing with redox status and inflammation response were mainly mediated through the PI3K-AKT pathway in the PCOS model.

Serum Klotho and insulin resistance: Insights from a cross-sectional analysis.

The prevalence of diabetes has surged globally, posing significant health and economic burdens. Insulin resistance underlies the initiation and development of type 2 diabetes. Klotho is a crucial endogenous antiaging factor, associated with atherosclerotic cardiovascular diseases, cancer, neurological disorders, and renal diseases. It additionally has a function in controlling glucose metabolism and holds promise as a new therapeutic target for diabetes. However, its relationship with insulin resistance remains unclear. This study utilizes the National Health and Nutrition Examination Survey (NHANES) 2007 to 2016 data to investigate the relationship between serum Klotho concentrations and insulin resistance. In this observational study, information from the NHANES spanning 2007 to 2016 was employed. The sample consisted of 6371 participants. Weighted linear regression model and chi-square tests were utilized to assess differences in continuous and categorical variables, respectively, among groups categorized by Klotho quartiles. The relationship between Klotho and HOMA-IR (homeostatic model assessment of insulin resistance) was studied using multiple linear regression. Smooth curve fitting was used to analyze nonlinear relationships and the inflection point was determined through a 2-stage linear regression method. After adjusting for multiple confounding factors, serum Klotho levels were found to be positively correlated with insulin resistance [0.90 (0.68, 1.13)]. This correlation is nonlinear and exhibits a saturation effect, with the inflection point identified at 1.24 pg/µL. When Klotho levels are below 1.24 pg/µL, for every unit increase in Klotho, HOMA-IR increases by 1.30 units. Conversely, when Klotho levels exceed 1.24 pg/µL, there is no correlation between HOMA-IR and Klotho. Subgroup analysis reveals that the relationship between HOMA-IR and Klotho varies depending on diabetes and body mass index (BMI). This positive correlation was most prominent in the obese nondiabetic population. There is a positive correlation between serum Klotho and insulin resistance.

Triglyceride Glucose Index is Associated with Ultrasonographic Fatty Liver Indicator in Children and Adolescents with Non-alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) is defined as chronic hepatic steatosis and is becoming prevalent, along with the increasing trend for obesity in children and adolescents. A non-invasive and reliable tool is needed to differentiate non-alcoholic steatohepatitis from simple steatosis. This study evaluated the association between the triglyceride glucose (TyG) index and the ultrasonographic fatty liver indicator (US-FLI), and the possibility of using the TyG index for prediction of severity of pediatric NAFLD. One hundred and twenty one patients who were diagnosed with NAFLD by ultrasonography were included. They were categorized into three groups according to body mass index (BMI). Ninety-two were obese, and 19 and 10 were overweight and normal weight, respectively. The homeostatic model assessment for insulin resistance (HOMA-IR) was highest in the group with obesity (p=0.044). The TyG index and US-FLI did not differ significantly among the three BMI groups (p=0.186). Fourteen (11.6%) of the 121 patients had US-FLI ≥6, in whom the BMI-SDS and TyG index were higher (p=0.017, p=0.004), whereas HOMA-IR did not differ significantly from the group with US-FLI <6 (p=0.366). US-FLI was associated with BMI-SDS and the TyG index. TyG index was significantly associated with US-FLI after adjustment for BMI-SDS. The cut-off value for the TyG index for predicting US-FLI ≥6 was 8.91, with an area under the curve of 0.785. TyG index was associated with the degree of hepatic steatosis, suggesting that it might be a useful tool for predicting the severity of pediatric NAFLD.

The effects of weight loss interventions on children and adolescents with non-alcoholic fatty liver disease: A systematic review and meta-analysis.

Overall, there is conflicting evidence regarding the beneficial effects of optimal lifestyle modification, particularly weight loss interventions, with nonalcoholic fatty liver disease (non-alcoholic fatty liver disease (NAFLD)). Therefore, this study investigated the effects of weight loss interventions on laboratory and clinical parameters in children and adolescents with NAFLD. Original databases (PubMed/MEDLINE, Web of Science, SCOPUS, and Embase) were searched using standard keywords to identify all controlled trials investigating the effects of weight loss interventions among NAFLD children and adolescents. Pooled weighted mean difference and 95% confidence intervals were achieved by random-effects model analysis. Eighteen eligible clinical trials were included in this systematic review and meta-analysis. The pooled findings showed that especially more intense weight loss interventions significantly reduced the glucose (p=0.007), insulin (p=0.002), homeostatic model assessment-insulin resistance (HOMA-IR) (p=0.003), weight (p=0.025), body mass index (BMI) (p=0.003), BMI z-score (p<0.001), waist circumference (WC) (p=0.013), triglyceride (TG) (p=0.001), and aspartate transaminase (AST) (p=0.027). However, no significant changes were found in total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), alanine transaminase (ALT), and hepatic steatosis grades (all p>0.05) following weight loss interventions. Weight loss interventions had significant effects on NAFLD-related parameters including glucose, insulin, HOMA-IR, weight, BMI, BMI z-score, WC, TG, and AST.

Associations between cardiometabolic indices and the risk of diabetic kidney disease in patients with type 2 diabetes

BackgroundThis study was designed to assess the associations between emerging cardiometabolic indices—the atherogenic index of plasma (AIP), the stress hyperglycemia ratio (SHR), the triglyceride-glucose (TyG) index, and the homeostasis model assessment of insulin resistance (HOMA-IR)—and the incidence of diabetic kidney disease (DKD) in type 2 diabetes (T2D) patients.MethodsWe consecutively enrolled 4351 T2D patients. The AIP, SHR, TyG index, and HOMA-IR were calculated from baseline parameters. DKD was defined as a urine albumin/creatinine ratio > 30 mg/g or an eGFR < 60 mL/min per 1.73 m. All participants were categorized into tertiles based on the cardiometabolic indices. Multivariate logistic regression models, restricted cubic splines, and receiver operating characteristic (ROC) curves were used for analysis.ResultsA total of 1371 (31.5%) patients were diagnosed with DKD. A restricted cubic spline showed a J-shaped association of the AIP and TyG index with DKD, a log-shaped association between HOMA-IR and DKD, and a U-shaped association between the SHR and DKD incidence. Multivariate logistic regression revealed that individuals in the highest tertile of the four cardiometabolic indices had a significantly greater risk of DKD than did those in the lowest tertile (AIP: OR = 1.08, 95% CI = 1.02–1.14, P = 0.005; SHR: OR = 1.42, 95% CI = 1.12–1.81, P = 0.004; TyG index: OR = 1.86, 95% CI = 1.42–2.45, P < 0.001; HOMA-IR: OR = 2.24, 95% CI = 1.52–3.30, P < 0.001). The receiver operating characteristic curves showed that the HOMA-IR score was better than other indices at predicting the risk of DKD, with an optimal cutoff of 3.532.ConclusionsElevated AIP, SHR, TyG index and HOMA-IR are associated with a greater risk of DKD in patients with T2D. Among these indices, the HOMA-IR score demonstrated the strongest association with and predictive value for DKD incidence.

Insulin:Glucagon Bipolar Axis in Obesity With a Glimpse Into Its Association With Insulin Resistance in Different Glucose Tolerance States.

Dysregulation of insulin and glucagon secretion alters the normal insulin:glucagon ratio (IGR) in type 2 diabetes mellitus, obesity, and metabolic syndrome. This study explores the scope of construing the role of these two diametrically opposing hormones on the glucose level not just in obesity but in different glucose tolerance states by looking at the hormone levels and at the insulin glucagon bipolar axis itself. This is an analytical cross-sectional study of 60 healthy adults consisting of an equal number of adults who are lean and adults who are obese. It was conducted at North Eastern Indira Gandhi Regional Institute of Health and Medical Sciences (NEIGRIHMS), located in Shillong City, Meghalaya, India. Fasting glucose, insulin, glucagon, and lipids were estimated. Postprandial estimation of glucose was done two hours after oral administration of 75 grams of glucose solution. The study demonstrated a state of hyperinsulinemia and hyperglucagonemia prevailing in obesity and all sub-categories of the group of persons who are obese. The study showed a higher fasting IGRin the group consisting of adults who were obese (with a mean of 4.11) when compared with the group of adults who are lean (with a mean of 2.24). Fasting IGRwas seen to increase with increasing levels of insulin resistance and increasing impairment in glucose tolerance. IGR showed a positive correlation with the homeostatic model assessment for insulin resistance (HOMA-IR) in the impaired fasting glucose (IFG) category and strongly in the impaired glucose tolerance (IGT) category. Hyperglucagonemia in the group of adult persons who are obese indicates a decreased sensitivity of alpha cells to insulin failing insulin to adequately suppress the secretion of glucagon. The study also demonstrated a positive correlation between IGR and HOMA-IR in obesity and all glucose tolerance states of the group of adults who are obese. It is telltale that the sturdier the insulin resistance, the higher the IGR.

Effect of Isocaloric, Time-Restricted Eating on Body Weight in Adults With Obesity : A Randomized Controlled Trial.

Time-restricted eating (TRE) lowers body weight in many studies. Whether TRE induces weight loss independent of reductions in calorie intake, as seen in rodent studies, is unknown. To determine the effect of TRE versus a usual eating pattern (UEP) on body weight in the setting of stable caloric intake. Randomized, isocaloric feeding study. (ClinicalTrials.gov: NCT03527368). Clinical research unit. Adults with obesity and prediabetes or diet-controlled diabetes. Participants were randomly assigned 1:1 to TRE (10-hour eating window, 80% of calories before 1 p.m.) or UEP (≤16-hour window, ≥50% of calories after 5 p.m.) for 12 weeks. Both groups had the same nutrient content and were isocaloric with total calories determined at baseline. Primary outcome was change in body weight at 12 weeks. Secondary outcomes were fasting glucose, homeostatic model assessment for insulin resistance (HOMA-IR), glucose area under the curve by oral glucose tolerance test, and glycated albumin. We used linear mixed models to evaluate the effect of interventions on outcomes. All 41 randomly assigned participants (mean age, 59 years; 93% women; 93% Black race; mean BMI, 36 kg/m2) completed the intervention. Baseline weight was 95.6 kg (95% CI, 89.6 to 101.6 kg) in the TRE group and 103.7 kg (CI, 95.3 to 112.0 kg) in the UEP group. At 12 weeks, weight decreased by 2.3 kg (CI, 1.0 to 3.5 kg) in the TRE group and by 2.6 kg (CI, 1.5 to 3.7 kg) in the UEP group (average difference TRE vs. UEP, 0.3 kg [CI, -1.2 to 1.9 kg]). Change in glycemic measures did not differ between groups. Small, single-site study; baseline differences in weight by group. In the setting of isocaloric eating, TRE did not decrease weight or improve glucose homeostasis relative to a UEP, suggesting that any effects of TRE on weight in prior studies may be due to reductions in caloric intake. American Heart Association.

The Association between the Plasma Phospholipid Profile and Insulin Resistance: A Population-Based Cross-Section Study from the China Adult Chronic Disease and Nutrition Surveillance.

The dysfunction of phospholipid metabolism enzymes and the change in membrane phospholipid composition are associated with insulin resistance, indicating that phospholipids play an important role in the regulation of insulin sensitivity. The reflection of phospholipid changes in blood might provide clues for both mechanism understanding and intervention. Using a targeted phospholipidomic approach, 199 phospholipid molecular species were identified and quantified in the plasma of 1053 middle-aged participants from a national investigation. The associations of the phospholipid matrix, clusters, and molecular species with insulin resistance were investigated. A significant association was confirmed between the phospholipid matrix and the homeostatic-model assessment of insulin resistance (HOMA-IR) by a distance-based linear model. Furthermore, three clustered phospholipid modules and 32 phospholipid molecular species were associated with HOMA-IR with the strict control of demographic and lifestyle parameters, family history of diabetes, BMI, WC, and blood lipid parameters. The overall decline in lysophosphatidylcholines (LPCs), the decrease in saturated lysophosphatidylethanolamines (LPEs), the decrease in polyunsaturated/plasmenyl phosphatidylcholines (PCs), and the increase in polyunsaturated phatidylethanolamines (PEs) were the prominent characters of plasma phospholipid perturbation associated with insulin resistance. This suggested that PC- and PE-related metabolic pathways were widely involved in the process of insulin resistance, especially the disorder of LPC acylation to diacyl-PC.

Association between serum levels of calcium, magnesium, iron and copper and insulin resistance in women with full blown and not-full blown phenotypes of polycystic ovary syndrome.

The aim of present study was to investigate the association between serum calcium, iron, magnesium, copper levels and insulin resistance in women with full blown phenotype of polycystic ovary syndrome (PCOS) compared to women with not-full blown phenotype. 104 women, aged 18-39, in the first phase of menstrual cycle, diagnosed with PCOS based on the Rotterdam Criteria, were qualified for the study. Patients were divided into two groups: group I contained women with full blown PCOS (phenotype A) and group II contained women with not-full blown PCOS (phenotypes B, C and D). Whole study population was divided on group X containing women with proper insulin sensitivity and group Y containing women with insulin resistance. The study found that women with full blown PCOS had lower level of magnesium compared with not-full blown phenotypes. Also, the level of copper was lower in group with proper insulin sensitivity compared to group with insulin resistance. Serum cooper content showed a negative correlation with Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) in group with full blown phenotype. Magnesium level showed positive correlation with level of calcium and cooper in group with proper insulin sensitivity. Level of iron content showed a negative correlation with sex hormone binding globulin (SHBG) and HOMA-IR showed a positive correlation with age and body mass index (BMI) in group with insulin resistance. Either level of calcium showed positive correlation with iron and cooper in group with insulin resistance.

Association of Acylcarnitines With Maternal Cardiometabolic Risk Factors Is Defined by Chain Length: The S-PRESTO Study

Abstract Context Due to the essential role of carnitine as an intermediary in amino acid, carbohydrate, and lipid metabolism, a detailed characterization of circulating and urinary carnitine concentrations will aid in elucidating the molecular basis of impaired maternal metabolic flexibility and facilitating timely intervention for expectant mothers. Objective To investigate the association of maternal plasma and urinary free carnitine and acylcarnitines with cardiometabolic risk factors. Methods Liquid chromatography tandem mass spectrometry–based quantification of free carnitine and acylcarnitines (C2-C18) was performed on 765 plasma and 702 urine samples collected at preconception, 26 to 28 weeks’ pregnancy, and 3 months postpartum in the Singapore PREconception Study of long-Term maternal and child Outcomes (S-PRESTO) cohort study. Results Plasma concentrations of free carnitine and acylcarnitines decreased coupled with increased renal clearance in pregnancy compared with preconception and postpartum. Renal clearance of carnitine increased with an increase in prepregnancy body mass index (ppBMI) and gestational weight gain. Plasma short-chain acylcarnitines were positively associated with ppBMI, irrespective of the physiological state, while medium- and long-chain acylcarnitines were negatively associated with ppBMI at preconception and postpartum but showed a positive association in pregnancy. Similarly, plasma short-chain acylcarnitines were positively associated with Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) whereas medium- and long-chain acylcarnitines were negatively associated with HOMA-IR at preconception and in pregnancy. Mothers who developed gestational diabetes mellitus during pregnancy had ∼10% higher plasma propionylcarnitine concentration and ∼18% higher urine tiglylcarnitine concentration than mothers with normal glucose metabolism at preconception. Conclusion This study provides the metabolic and physiological basis of maternal carnitine homeostasis, which can be used in assessment of maternal cardiometabolic health at preconception to improve pregnancy outcomes.

Patients with autoimmune liver disease have glucose disturbances that mechanistically differ from steatotic liver disease.

Autoimmune liver diseases are associated with an increased risk of diabetes, yet the underlying mechanisms remain unknown. In this cross-sectional study, we investigated the glucose-regulatory disturbances in patients with autoimmune hepatitis (AIH, n = 19), primary biliary cholangitis (PBC, n = 15), and primary sclerosing cholangitis (PSC, n = 6). Healthy individuals (n = 24) and patients with metabolic dysfunction-associated steatotic liver disease (MASLD, n = 18) were included as controls. Blood samples were collected during a 120-min oral glucose tolerance test. We measured the concentrations of glucose, C-peptide, insulin, glucagon, and the two incretin hormones, glucose insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP-1). We calculated the homeostasis model assessment of insulin resistance (HOMA-IR), whole body insulin resistance (Matsuda index), insulin clearance, and insulinogenic index. All patient groups had increased fasting plasma glucose and impaired glucose responses compared with healthy controls. Beta-cell secretion was increased in AIH, PBC, and MASLD but not in PSC. Patients with AIH and MASLD had hyperglucagonemia and hepatic, as well as peripheral, insulin resistance and decreased insulin clearance, resulting in hyperinsulinemia. Patients with autoimmune liver disease had an increased GIP response, and those with AIH or PBC had an increased GLP-1 response. Our data demonstrate that the mechanism underlying glucose disturbances in patients with autoimmune liver disease differs from that underlying MASLD, including compensatory incretin responses in patients with autoimmune liver disease. Our results suggest that glucose disturbances are present at an early stage of the disease.NEW & NOTEWORTHY Patients with autoimmune liver disease but without overt diabetes display glucose disturbances early on in their disease course. We identified pathophysiological traits specific to these patients including altered incretin responses.

Study of association of leptin with leukocyte telomere length in a Chinese rural population

BackgroundPrevious studies have demonstrated the relationship between adipocyte factors, insulin resistance, and other indicators with telomere length. However, these studies did not consider the influence of changes in different indicators on telomere length over time. Therefore, the aim of this study is to elucidate the impact of changes in adipocyte factors, HOMA-IR, and other indicators on the dynamic variation of telomere length.MethodsThe data were from a cohort study conducted in Ningxia, China. A total of 1624 subjects were analyzed. Adipokines and relative leukocyte telomere length (RLTL) were measured, and changes in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), Homeostatic Model Assessment for β-Cell Function (HOMA-β), and Quantitative Insulin Sensitivity Check Index (QUICKI) were calculated. Generalized linear models evaluated associations between changes in adipokines and RLTL changes. Furthermore, univariate analyses examined the effects of changes in adipokines and insulin resistance indicators on ΔRLTL.ResultsThe research findings indicate that females generally have shorter telomeres compared to males. In comparison to the low-level group of Δleptin (LEP), the high-level group of ΔLEP shows a negative correlation with ΔRLTL (B=-1.32, 95% CI (-2.38, -0.27)). Even after multivariable adjustments, this relationship persists (B=-1.31, 95% CI (-2.24, -0.23)). Further analysis reveals that after adjusting for ΔHOMA-IR, ΔHOMA-β, and ΔQUICKI, the high-level group of ΔLEP still exhibits a significant negative correlation with ΔRLTL (B=-1.37, 95% CI (-2.43, -0.31)). However, the interaction effects between ΔHOMA-IR, ΔHOMA-β, ΔQUICKI, and ΔLEP do not affect ΔRLTL.ConclusionsElevated levels of leptin were significantly correlated with shortened telomere length. This suggests that increased leptin levels may impact overall individual health by affecting telomere length, underscoring the importance of measures to reduce leptin levels to mitigate the onset and progression of related diseases.

The Expression of MAFB Gene in Circulating Monocytes Is Related to Chronic Inflammatory Status in T2DM Patients.

Immune cell-mediated chronic inflammation is one of the causes of type 2 diabetes mellitus (T2DM). Therefore, identifying inflammatory markers in circulating immune cells is highly important for predicting insulin resistance (IR) and the occurrence of T2DM. In this study, we discovered that differentially expressed genes (DEGs) in peripheral blood mononuclear cells (PBMCs) from T2DM patients were associated with innate immunity and chronic inflammatory responses through bulk transcriptome sequencing (bulk RNA-seq). Gene integration analysis revealed that nine DEGs were upregulated, and receiver operating characteristic (ROC) curve analysis revealed that V-maf musculoaponeurotic fibrosarcoma oncogene homolog B (MAFB), a candidate biomarker, has a certain predictive value for T2DM. In population-based cohort studies, we found that MAFB expression was significantly upregulated in the PBMCs of T2DM patients and was significantly correlated with homeostasis model assessment of IR (HOMA-IR), tumor necrosis factor-α (TNF-α), adiponectin (Adipoq), etc. We further evaluated the sensitivity and specificity of MAFB and other clinical parameters for predicting and diagnosing T2DM and found that MAFB expression in PBMCs had a positive effect on the prediction and diagnosis of T2DM. Finally, single-cell RNA sequencing (scRNA-seq) analysis revealed that the increase in MAFB expression was mainly in nonclassical monocytes. Our results suggest that increased MAFB expression in circulating monocytes may mediate chronic inflammatory status in patients with T2DM. Therefore, MAFB gene expression in circulating monocytes has certain clinical significance for predicting and assisting in the diagnosis of T2DM.

Insulin Resistance-Related Cardiometabolic Risk Among Nondiabetic Childbearing Age Females.

Background: This study evaluates insulin resistance prevalence in young females without diabetes, assessing risk factors and adiposity indices for early detection of cardiometabolic disorders. Methods: A cross-sectional study was conducted, involving 282 females aged 18-35 years from suburban and rural areas of Sri Lanka. Anthropometric measurements [height, weight, waist circumference (WC)] were obtained and biochemical parameters [fasting glucose, insulin, insulin resistance (IR), total cholesterol, high-density lipoproteins, (HDL), low-density lipoproteins, triglycerides] were measured. The anthropometric and biochemical data were compared between the groups of normal weight controls and overweight/obese cases, as well as between females with or without IR. Results: The prevalence of IR in controls and cases were 48.6% and 57.1%, respectively. Both groups had mean Homeostasis Model Assessment-IR values greater than the normal cutoff value of 2.5. Females with IR showed higher prevalence of dyslipidemia than those without IR. Compared to the controls (2.81%), the prevalence of metabolic syndrome (MetS) was substantially greater among cases (46.42%). Both groups showed a statistically significant association between IR and MetS, but the association was considerably stronger in cases [r = 0.616, odds ratio (OR) >8] than in controls (r = 0.175, OR >1). Controls exhibited lower HDL levels, hypertriglyceridemia, and elevated IR levels (P < 0.05), and their ORs for acquiring MetS were >2, <1, and >3, respectively. Importantly, overweight/obese cases exhibited a significant association (P < 0.05) with all the MetS risk variables. Visceral adiposity index (VAI) proves to be a precise measurement for identifying IR and cardiovascular disease (CVD) among young females (Z = -3.651), surpassing the accuracy of other indices. Body mass index, body round index, a body shape index, and WC were also reliable measurements to assess IR and the risk of CVD (P < 0.05). Conclusion: The study underscores the importance of assessing IR in nondiabetic young females to identify early cardiometabolic risks. VAI emerges as a precise measurement for identifying IR and CVD risk, surpassing the accuracy of other indices.

StarD5 levels of expression correlate with onset and progression of steatosis and liver fibrosis.

Insufficient expression of steroidogenic acute regulatory-related lipid transfer protein 5 (StarD5) on liver cholesterol/lipid homeostasis is not clearly defined. The ablation of StarD5 was analyzed in mice on a normal or Western diet (WD) to determine its importance in hepatic lipid accumulation and fibrosis compared with wild-type (WT) mice. Rescue experiments in StarD5-/- mice and hepatocytes were performed. In addition to increased hepatic triglyceride (TG)-cholesterol levels, global StarD5-/- mice fed a normal diet displayed reduced plasma triglycerides and liver very low-density lipoprotein (VLDL) secretion as compared with WT counterparts. Insulin levels and homeostatic model assessment for insulin resistance (HOMA-IR) scoring were elevated, demonstrating developing insulin resistance (IR). WD-fed StarD5-/- mice upregulated WW domain containing transcription regulator 1 (TAZ or WWTR1) expression with accelerated liver fibrosis when compared with WD-fed WT mice. Suppression of oxysterol 7α-hydroxylase (CYP7B1) coupled with chronic accumulation of toxic oxysterol levels correlated with presentation of fibrosis. "Hepatocyte-selective" StarD5 overexpression in StarD5-/- mice restored expression, reduced hepatic triglycerides, and improved HOMA-IR. Observations in two additional mouse and one human metabolic dysfunction-associated steatotic liver disease (MASLD) model were supportive. The downregulation of StarD5 with hepatic lipid excess is a previously unappreciated physiological function appearing to promote lipid storage for future needs. Conversely, lingering downregulation of StarD5 with prolonged lipid-cholesterol excess accelerates fatty liver's transition to fibrosis; mediated via dysregulation in the oxysterol signaling pathway.NEW & NOTEWORTHY We have found that deletion of the cholesterol transport protein StarD5 in mice leads to an increase in insulin resistance and lipid accumulation due to the upregulation of lipid synthesis and decrease VLDL secretion from the liver. In addition, deletion of StarD5 increased fibrosis when mice were fed a Western diet. This represents a novel pathway of fibrosis development in the liver.

Association between hypotension during pancreatectomy and development of postoperative diabetes.

With advancements in long-term survival after pancreatectomy, post-pancreatectomy diabetes has become a concern, and the risk factors are not established yet. Pancreatic islets are susceptible to ischemic damage, though there is a lack of clinical evidence regarding glycemic deterioration. To investigate association between hypotension during pancreatectomy and development of post-pancreatectomy diabetes. In this retrospective, longitudinal cohort study, we enrolled patients without diabetes who underwent distal pancreatectomy or pancreaticoduodenectomy between January 2005 and December 2018, from two referral hospitals in Korea. Intraoperative hypotension [IOH] was defined as a 20% or greater reduction in systolic blood-pressure. The primary and secondary outcomes were incident diabetes and postoperative Homeostatic Model Assessment [HOMA] indices. We enrolled 1,129 patients (average age, 59 years; 49% men; 35% distal pancreatectomy). IOH occurred in 83% (median duration, 25 minutes; interquartile range [IQR], 5-65). During a median follow-up of 3.9 years, diabetes developed in 284 patients (25%). The cumulative incidence of diabetes was proportional to increases in the duration and depth of IOH (P < 0.001). For the median duration in an IOH when compared to a reference time of 0 minute, the hazard ratio [HR] was 1.48 (95% CI, 1.14-1.92). The effect was pronounced with distal pancreatectomy compared to pancreaticoduodenectomy. Furthermore, the duration of IOH was inversely correlated with 1-year HOMA beta-cell function (P < 0.002), but not with HOMA insulin resistance. These results support the hypothesis that IOH during pancreatectomy may elevate risk of diabetes by inducing beta cell insufficiency.