Homeostasis Model Assessment Of Insulin Resistance Research Articles

Kidney Dysfunction Prediction by Serum Adropin in Type 2 Diabetes Iraqi Patients

Abstract Background: Diabetic nephropathy (DN) is a problem that arises from microvascular complications with type 2 diabetes mellitus (T2DM). It especially denotes the deterioration of renal function. Adropin, a regulatory peptide hormone, has attracted interest for its potential role in regulating metabolism, specifically glucose metabolism and insulin resistance. Objective: To assess Adropin’s role in the identification and severity of T2DM nephropathy. Methods: A cross-sectional study which involved an 88 patients with DN was conducted in the National Diabetes Center/Mustansiriyah University during the period from October 2023 to April 2024. Body mass index, blood analysis for sugar levels, lipid profile, renal function test, and albumin to creatinine ratio in urine were conducted. In addition, the content of human adropin was evaluated using an enzyme-linked immunosorbent assay. Results: Much more fasting blood sugar, glycated hemoglobin, insulin, homeostasis model assessment insulin resistance, cholesterol, triglycerides, low-density lipoprotein (LDL) and very LDL, urea, and creatinine were found in the microalbuminuria and macroalbuminuria groups of DN patients than in the normoalbuminuria group. The amount of adropin in the blood was lowered in people with microalbuminuria and macroalbuminuria (245.91 ± 59.47 and 179.86 ± 51.96 pg/ml, respectively) than in people with normoalbuminuria (377.97 ± 98.69 pg/ml) as well. While the subject attempts to identify the difference between the groups of DN, adropin works very well and is very sensitive. Conclusion: This study establishes a correlation between reduced adropin levels and impaired kidney function in individuals diagnosed with T2DM. Adropin content in the serum is able to serve as a biomarker for the early recognition of DN, by its role in glucose metabolism and insulin resistance.

Markers for Pressure Injury Risk in Individuals with Chronic Spinal Cord Injury: A Pilot Study.

To identify markers associated with pressure injury (PrI) history in individuals with spinal cord injury (SCI) using two approaches: skin blood flow (SBF) response toward localized heating, and serum marker for insulin resistance. For this cross-sectional, observational study of adults with chronic traumatic SCI at T12 and above, researchers recruited two groups of participants: with history of PrI (group 1), and without history of PrI (group 2). The study protocol included obtaining fasting blood samples and measurement of SBF at bilateral heels with localized heating of 42 °C for 30 minutes from all participants. Primary SBF outcomes were initial peak and plateau SBF normalized to baseline SBF. The primary outcome for insulin resistance was Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), calculated from fasting plasma glucose and insulin. Secondary outcomes included demographic and SCI information. Researchers used the Fisher exact test and Wilcoxon-Mann-Whitney test to compare the intergroup difference of categorical and continuous variables, respectively. Sixteen adults completed this study (group 1, n = 7; group 2, n = 9). In comparison with group 2, group 1 had significantly higher HOMA-IR (3.90 ± 0.71 vs 1.45 ± 0.71), suggesting higher insulin resistance, and longer duration of injury (22.54 ± 7.24 vs 7.98 ± 6.58 years). There were no between-group differences in SBF or other secondary outcomes. HOMA-IR is a novel serum index associated with PrI history in persons with chronic SCI. Future longitudinal study is warranted to examine the role of insulin resistance in increasing PrI risk for the SCI population.

Modulation of placental angiogenesis by metformin in a rat model of gestational diabetes.

Gestational diabetes mellitus (GDM) significantly disrupts placental structure and function, leading to complications such as intrauterine growth restriction (IUGR) and preeclampsia. This study aimed to investigate the effects of GDM on placental histology, angiogenesis, and oxidative stress, as well as evaluate metformin's protective role in mitigating these changes. A total of 60 pregnant Sprague-Dawley rats were divided into four groups: control, metformin-treated, GDM, and GDM with metformin. GDM was induced using streptozotocin (STZ) at 40mg/kg, and metformin was administered at 200mg/kg from gestational day (GD) 4 to GD17. Blood glucose and insulin levels were assessed, and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) was calculated. Placentae were weighed and subjected to histological, immunohistochemical, and molecular analyses, focusing on key angiogenesis markers (VEGF, VEGFR, CD31, KLF2) and oxidative stress indicators (MDA, eNOS). GDM increased placental weight, angiogenesis (elevated VEGF, VEGFR, CD31), and oxidative stress (elevated MDA, eNOS). Histopathological changes included villous edema, membrane rupture, and hemosiderin deposition. Metformin treatment reduced placental weight; normalized VEGF, KLF2, and PlGF expression; and improved placental architecture. Additionally, oxidative stress was significantly reduced in metformin-treated GDM rats. In conclusion, GDM induces placental abnormalities, promoting excessive angiogenesis and oxidative stress, potentially leading to IUGR and other complications. Metformin showed protective effects by reducing placental overgrowth and restoring vascular and oxidative balance. These findings suggest that metformin may play a therapeutic role in improving placental health in GDM pregnancies, warranting further investigation into its long-term effects on fetal development and maternal health.

The Association Between Glucose Variability and Insulin Parameters in Gestational Diabetes Diagnosed After 24 Gestational Weeks

Background/Objectives: Recently, it was reported that glucose variability (GV) calculated using the 75 g oral glucose tolerance test (OGTT) is associated with adverse perinatal outcomes. However, its role in gestational diabetes mellitus (GDM) remains unclear. We investigated the association between GV and insulin parameters in Japanese women diagnosed with GDM after 24 weeks of gestation (late GDM). Methods: A total of 280 mothers with late GDM cared for at Keio University Hospital were included in this study. Using 75 g OGTT, the initial increase and subsequent decrease were calculated as the GV. Results: The initial increase was significantly positively associated with 1 h plasma glucose level (PG) and 2 h PG with 75 g OGTT (p < 0.001), but fasting PG, insulinogenic index (IGI), and homeostasis model assessment—insulin resistance were negatively associated with the initial increase (all p < 0.001). The subsequent decrease was significantly positively correlated with 1 h PG (p < 0.001) but negatively correlated with 2 h PG (p < 0.001), IGI (p = 0.009), and the whole-body insulin sensitivity index derived from the OGTT (p = 0.02). Insulin Secretion-Sensitivity Index-2 was not associated with an initial increase or subsequent decrease. Conclusions: Since the initial increase might reflect insulin secretion and the subsequent decrease might reflect insulin sensitivity in Japanese women with late GDM, GV could alter several insulin parameters. Further studies are required to investigate the usefulness of GV in the management of GDM.

The association of visceral and subcutaneous fat areas with phenotypic age in non-elderly adults, mediated by HOMA-IR and HDL-C

BackgroundAgeing results in diminished adaptability, as well as declines in physiological and psychological functions and resilience. The epigenetic clock ‘Phenotypic Age’ (PhenoAge) represents ‘preclinical ageing’. Phenotypic Age Acceleration (PhenoAgeAccel) is defined as the residual from a linear regression model predicting PhenoAge on the basis of chronological age. Abdominal subcutaneous adipose tissue, visceral adipose tissue, the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), and high-density lipoprotein cholesterol (HDL-C) have all been shown to correlate with ageing; however, the connections between these factors and PhenoAge are still insufficiently investigated.MethodsData for this study were sourced from the National Health and Nutrition Examination Survey (2015–2018), comprising 2580 participants. Complex survey designs were considered. To examine the association between body fat area and PhenoAgeAccel, logistic regression was applied. Additionally, subgroup analysis was used to identify variations in population characteristics. The dose‒response relationship between body fat area and PhenoAgeAccel was determined via restricted cubic spline analysis. Mediation and interaction analyses were further employed to investigate the roles of the HOMA-IR and HDL-C in this association.ResultsIn nonelderly adults, the relationships between body fat area and PhenoAgeAccel differed chronological age. For abdominal subcutaneous fat area (SFA), this relationship was nonlinear in individuals aged 18–44 years and 45–59 years, with thresholds of 2.969 m² and 3.394 m², respectively. In contrast, a nonlinear relationship of visceral fat area (VFA) with PhenoAgeAccel was observed in individuals aged 18–44 years, while this relationship was linear in individuals aged 45–59 years, with thresholds of 0.769 m² and 1.220 m², respectively. Mediation effect analysis revealed that the HOMA-IR had a more pronounced mediation effect in individuals aged 18–44 years, accounting for 13.4% of the relationship between VFA and PhenoAgeAccel and 6.9% of the relationship between SFA and PhenoAgeAccel. Conversely, HDL-C had a greater mediating effect in individuals aged 45–59 years, accounting for 21.7% of the relationship between VFA and PhenoAgeAccel and 11.6% of the relationship between abdominal SFA and PhenoAgeAccel. HOMA-IR ≥ 2.73 or VFA > 0.925 m², as well as HOMA-IR ≥ 2.73 or abdominal SFA > 3.137 m², accelerated PhenoAge, whereas 1.60 < HDL-C ≤ 3.90 mmol/L combined with abdominal SFA ≤ 3.137 m² or VFA ≤ 0.925 m² decelerated PhenoAge.ConclusionIn this study, the nonlinear relationships among abdominal SFA, VFA, and PhenoAgeAccel were elucidated, while characteristic thresholds across different age groups were identified. The results of this study emphasize the complex influence of fat distribution on the ageing process and refine the roles of HOMA-IR and HDL-C in various age cohorts. These findings provide a biological basis for future screening for accelerated ageing and appropriate intervention in high-risk populations and offer valuable insights for guiding personalized clinical interventions and health management strategies.

Nonlinear association between depressive symptoms and homeostasis model assessment of insulin resistance: a cross-sectional analysis in the American population

BackgroundDepressive symptom, a pervasive mental health disorder, has garnered increasing attention due to its intricate interconnections with various physiological processes. One emerging avenue of investigation delves into the potential association between depressive symptom and Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), a parameter reflecting insulin resistance. The intricate interplay between these two domains holds promising implications for understanding the multifaceted nature of depressive symptom and its impact on metabolic health.MethodsWe used weighted multivariable logistic regression models with subgroup analysis to explore the relationship between depressive symptom and homeostasis model assessment of insulin resistance. Non-linear correlations were explored using fitted smoothing curves. Then, we constructed a two-piece linear regression model and performed a recursive algorithm to calculate the inflection point.ResultsThe study included 20,282 participants in the United States. In the regression model adjusted for all confounding variables, the odds ratio (OR) for the correlation between depressive symptom and the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) was 1.01 (95% CI: 1.00, 1.01). However, a significant discrepancy between trend tests and regression analyses suggests a potential non-linear relationship between depressive symptom and the assessment of insulin resistance using the Homeostasis Model. Constrained cubic spline analysis confirmed this non-linear relationship, identifying an inflection point at 10.47. Before the inflection point, depressive symptom exhibited a significantly positive correlation with the assessment of insulin resistance using the Homeostasis Model. However, after the inflection point, a negative correlation was observed, though it did not reach statistical significance.ConclusionWe found a curve-like relationship between depressive symptom and homeostasis model assessment of insulin resistance.

Effects of silymarin on insulin resistance and sensitivity: A systematic review and meta-analysis of randomized controlled trials.

This study aims to evaluate the effect of silymarin on insulin resistance and insulin sensitivity through a systematic review and meta-analysis of randomized controlled trials (RCTs). We searched PubMed, Embase, Web of Science, and Cochrane Library up to September 2024 for relevant RCTs. The intervention required silymarin supplementation for at least 4weeks. Primary outcomes were homeostatic model assessment of insulin resistance (HOMA-IR) and fasting insulin (FI), while secondary outcomes included quantitative insulin sensitivity check index (QUICKI). Bias risk was assessed using Cochrane RoB 2. Subgroup analyses were based on disease type, duration, and dosage. Sensitivity and publication bias analyses were conducted using Egger's and Begg's tests. Statistical analysis and meta-analysis were performed using Stata 15.1. Six studies with 673 participants from Iran, Egypt, and Italy were included. All studies had low risk of bias. Meta-analysis showed that Silybum marianum significantly improved HOMA-IR (WMD = -2.29, 95% CI: -4.55 to -0.03, p=0.047) but had no effect on FI (WMD = -2.56, 95% CI: -7.60 to 2.48, p=0.862). Subgroup analyses revealed improvements in HOMA-IR for T2DM and diabetics with alcoholic cirrhosis, but no effect in non-alcoholic fatty liver disease (NAFLD) patients. QUICKI did not show significant changes in any group. Only one study reported changes in QUICKI. The results indicated that, compared to the placebo, silymarin improved insulin sensitivity in patients with type 2 diabetes mellitus (T2DM). In conclusion, the results of this study indicate that there is limited evidence supporting the effectiveness of silymarin in improving HOMA-IR and FI levels in metabolic diseases, and it generally does not appear to significantly improve these parameters. Future studies should aim to increase the number of high-quality RCTs to further validate the efficacy and safety of silymarin, as well as to explore its underlying mechanisms.

Association of different insulin resistance surrogates with all-cause and cardiovascular mortality among the population with cardiometabolic multimorbidity

BackgroundThe coexistence of cardiometabolic diseases (CMDs), defined as cardiometabolic multimorbidity (CMM), has been shown to significantly elevate mortality risk. Insulin resistance (IR) is one of the main contributing factors to the pathogenesis of CMM. Although several surrogates for IR are employed in clinical evaluations, their relationship with mortality in individuals with CMM remains unclear. This study aimed to investigate the associations between various IR surrogates and mortality in individuals with CMM, and to evaluate their prognostic value.MethodsThis study enrolled 1093 patients diagnosed with CMM. We developed five surrogate markers to assess IR levels: triglyceride-glucose (TyG) index, TyG-waist circumference (TyG-WC), TyG-waist height ratio (TyG-WHtR), homeostatic model assessment of insulin resistance (HOMA-IR), and metabolic score for insulin resistance (METS-IR). To investigate the associations between different IR surrogates and both all-cause and cardiovascular mortality, multivariable Cox proportional hazards models were applied. We employed restricted cubic splines to examine non-linear associations, and Cox models were developed on either side of the inflection point for additional investigation. Meanwhile, the predictive values of five IR surrogates were further assessed.ResultsOf the 477 all-cause deaths that occurred during a median follow-up of 5.8 years, 197 were related to cardiovascular disease. Among five surrogate markers of IR, the TyG index was the only one that significantly correlates with both all-cause and cardiovascular mortality. The threshold value for both types of mortality was 8.85. A TyG index beneath the inflection point exhibits an inverse correlation with cardiovascular mortality (HR 0.483; 95% CI = 0.281–0.831) and all-cause mortality (HR 0.519; 95% CI = 0.368–0.732). On the other hand, when the TyG index surpassed the inflection point, it demonstrated a positive correlation with cardiovascular mortality (HR 1.413; 95% CI = 1.075–1.857) and all-cause mortality (HR 1.279; 95% CI = 1.070–1.529). Based on the analysis of receiver operating characteristics, the TyG index has been recognized as a dependable predictor of survival outcomes.ConclusionsThis study emphasizes the prognostic significance of IR surrogates, particularly the TyG index, in predicting mortality among individuals with CMM. The TyG index constitutes a crucial element in the development of management and intervention strategies for these patients.Graphical abstract

Study protocol of the PRINCESS trial—PReoperative INtermittent fasting versus CarbohydratE loading to reduce inSulin resiStance versus standard of care in orthopaedic patients: a randomised controlled trial

IntroductionSurgical trauma induces a metabolic stress response, resulting in reduced insulin sensitivity and hyperglycaemia. Postoperative insulin resistance (IR) is associated with postoperative complications, and extended preoperative fasting may further aggravate...

Longitudinal association between DNA methylation and type 2 diabetes: findings from the KORA F4/FF4 study

BackgroundType 2 diabetes (T2D) has been linked to changes in DNA methylation levels, which can, in turn, alter transcriptional activity. However, most studies for epigenome-wide associations between T2D and DNA methylation comes from cross-sectional design. Few large-scale investigations have explored these associations longitudinally over multiple time-points.MethodsIn this longitudinal study, we examined data from the Cooperative Health Research in the Region of Augsburg (KORA) F4 and FF4 studies, conducted approximately seven years apart. Leucocyte DNA methylation was assessed using the Illumina EPIC and 450K arrays. Linear mixed-effects models were employed to identify significant associations between methylation sites and diabetes status, as well as with fasting plasma glucose (FPG), hemoglobin A1c (HbA1c), homoeostasis model assessment of beta cell function (HOMA-B), and homoeostasis model assessment of insulin resistance (HOMA-IR). Interaction effects between diabetes status and follow-up time were also examined. Additionally, we explored CpG sites associated with persistent prediabetes or T2D, as well as the progression from normal glucose tolerance (NGT) to prediabetes or T2D. Finally, we assessed the associations between the identified CpG sites and their corresponding gene expression levels.ResultsA total of 3,501 observations from 2,556 participants, with methylation measured at least once across two visits, were included in the analyses. We identified 64 sites associated with T2D including 15 novel sites as well as known associations like those with the thioredoxin-interacting protein (TXNIP) and ATP-binding cassette sub-family G member 1 (ABCG1) genes. Of these, eight CpG sites exhibited different rates of annual methylation change between the NGT and T2D groups, and seven CpG sites were linked to the progression from NGT to prediabetes or T2D, including those annotated to mannosidase alpha class 2a member 2 (MAN2A2) and carnitine palmitoyl transferase 1 A (CPT1A). Longitudinal analysis revealed significant associations between methylation and FPG at 128 sites, HbA1c at 41 sites, and HOMA-IR at 57 sites. Additionally, we identified 104 CpG-transcript pairs in whole blood, comprising 40 unique CpG sites and 96 unique gene transcripts.ConclusionsOur study identified novel differentially methylated loci linked to T2D as well as to changes in diabetes status through a longitudinal approach. We report CpG sites with different rates of annual methylation change and demonstrate that DNA methylation associated with T2D is linked to following transcriptional differences. These findings provide new insights into the molecular mechanisms of diabetes development.Graphical abstract

Effects of Supplementation With Different Specificities of Dietary Fiber on Health-Related Indicators in Adults With Overweight or Obesity: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

Dietary fiber (DF) exhibits variations in its chemical and physical complexity, as well as in its utilization by the gut microbiota. However, the impact of these differences on the health status of adults with overweight or obesity remains unclear. This meta-analysis aimed to explore the varying effects of supplementing with different specificities of DF on the health of adults with overweight or obesity, providing guidance on selecting DF supplementation to improve health status. The literature search encompassed 4 electronic databases-PubMed, Cochrane Library, Web of Science, and EMBASE-and was conducted between January 1, 2012, and November 10, 2023. Randomized controlled trials comparing DF with placebo treatment, without energy restriction, were included. Two independent reviewers extracted data using a standardized form, resolving discrepancies through discussion. The data included study characteristics, participant demographics, DF specifications, and outcome measures. Random-effects models and the generic inverse variance method were used to analyze data, assuming varying outcomes based on DF specificity. Meta-regression assessed the impact of population, duration, and dosage. Publication bias was evaluated using funnel plots and Egger's and Begg's tests. The analysis included 34 trials (n = 1804) examining DF supplementation at 1.5 to 40 g/day for 3 to 16 weeks. DF supplementation significantly reduced glycated hemoglobin (HbA1c) by 0.13%, fasting insulin by 0.82 μIU/mL, and homeostatic model assessment of insulin resistance (HOMA-IR) by 0.33 in adults with overweight or obesity. Subgroup analyses based on DF specificity revealed differences in effects on HbA1c, fasting insulin, and systolic blood pressure. The low-specificity subgroup showed significant heterogeneity in body weight, body mass index, HbA1c, fasting insulin, and HOMA-IR, with a decrease in fasting insulin by 1.09 μIU/mL. The low-to-intermediate-specificity subgroup had reductions in HbA1c by 0.8%, fasting insulin by 2.08 μIU/mL, and HOMA-IR by 0.61. The intermediate-specificity subgroup experienced a 2.85-kg decrease in body weight and a 9.03-mg/dL increase in LDL cholesterol. The mixed subgroup showed an increase in systolic blood pressure by 3.85 mmHg. Supplementing with different specificities of DF may have distinct effects on health-related indicators in adults with overweight or obesity. Considering individuals' gut microbiota composition and specific health goals is recommended when selecting DF supplementation for adults with overweight or obesity. PROSPERO registration no. CRD42023432920.

Decreased Levels of Insulin-Regulated Aminopeptidase (IRAP) in Gestational Diabetes Mellitus: A Prospective Cohort Study

Background: Insulin-regulated aminopeptidase (IRAP) is involved in insulin sensitivity and glucose metabolism and is important in the pathophysiology of type 2 diabetes. Serum IRAP levels are strongly associated with type 2 diabetes and insulin resistance. The aim of this study was to evaluate the IRAP level as a potential biomarker for the early diagnosis and management of insulin resistance in women with gestational diabetes mellitus (GDM). Methods: This cohort study included 40 women with GDM and 40 women with healthy pregnancies. Maternal serum IRAP levels were measured with enzyme-linked immunosorbent assay (ELISA) and compared between the two groups. Results: The mean serum IRAP level was significantly lower in the GDM group (0.73 ± 0.12 ng/mL) compared to the controls (0.92 ± 0.10 ng/mL) (p = 0.001). Pairwise comparisons indicated, that diet modified and insulin treated GDM subgroups had significantly lower serum IRAP levels than the control group (p &lt; 0.017 and p &lt; 0.017, respectively). Serum IRAP levels showed significant negative correlations with fasting glucose, insulin, homeostatic model assessment of insulin resistance (HOMA-IR) levels and hemoglobin A1c (HbA1c) (r = –0.541, p = 0.001; r = –0.447, p = 0.001; r = –0.584, p = 0.001; r = –0.361, p = 0.001). The optimum serum IRAP cut-off value was calculated to be 0.857 ng/mL, with a sensitivity of 85% and a specificity of 80% for the prediction of GDM (p = 0.001). Conclusions: The serum IRAP level in pregnant women diagnosed with GDM was significantly lower than in healthy pregnant women. Moreover, the serum IRAP level was negatively correlated with the levels of insulin, HbA1c, and HOMA-IR. These findings suggest that low serum IRAP level could be a novel biomarker for the prediction of GDM. Clinical Trial registration: The study has been registered on https://classic.clinicaltrials.gov/ (registration number: NCT06716320).

Woxuanzhongzhou formula improves DHEAS and high-fat diet-induced IR and anovulatory mice via AMPK/PGC1- α/Irisin pathway

BackgroundPolycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder in women of reproductive age. Anovulation is one of the most important clinical features of PCOS, and insulin resistance (IR) is one of the critical pathogenic factors. Woxuanzhongzhou (WXZZ) is a traditional herbal formulation that has shown efficacy in treating PCOS combined with IR, but the underlying mechanism is not clear. The aim of this study was to investigate the molecular mechanism of WXZZ on dehydroepiandrosterone sulfate and high fat diet induced PCOS with IR mice.Methods40 female C57BL/6 mice were randomized to 4 groups: control group, model group, metformin group, and WXZZ group. Some mice is induced by dehydroepiandrosterone sulfate (DHEA) and high-fat diet (HFD) for 3 weeks. Following model induction, metformin and WXZZ were administered by gavage. Body weight, fasting blood glucose (FBG), fasting insulin (FINS) levels, the homeostatic model assessment of insulin resistance (HOMA-IR), and gonadal hormones were measured. Estrous cycles were monitored. The structure of the gastrocnemius muscle and subcutaneous fatty tissue were also evaluated. Additionally, serum irisin and non-esterified fatty acids (NEAF) levels and the protein and gene expression levels of AMPK, PGC1-α, FNDC5, irisin in the gastrocnemius muscle and CaMKK, AMPK, PGC1-α, UCP1 in fat were analyzed.ResultsThe DHEA + HFD + WXZZ group exhibited significant improvements in several key parameters compared to the DHEA + HFD group. WXZZ ameliorated endocrine and metabolic disorders, resumed estrous cycle in DHEAS and high-fat diet-induced IR and anovulatory mice. Significant reductions were observed in body weight, serum testosterone, luteinizing hormone, luteinizing hormone/ follicle-stimulating hormone ratio, FINS, and HOMA-IR. Additionally, WXZZ promoted irisin expression and secretion by up-regulating the protein and gene AMPK/PGC1-α/FNDC5 expression in gastrocnemius muscle and up-regulated the protein and gene CaMKK/AMPK/PGC1-α/UCP1 expression in fat. WXZZ inhibited the overproduction of serum NEFA, and reduced lipid accumulation. Structural analysis of the gastrocnemius muscle and adipose tissue revealed partial restoration.ConclusionWXZZ exhibits therapeutic effects in DHEAS and high-fat diet-induced IR and anovulatory mice. These effects may be mediated through the activation of AMPK/PGC1-α pathway in muscle to promote the secretion of irisin.

Shiftwork and insulin resistance in professional drivers: exploring the association using non-insulin-based surrogate measures

BackgroundPrevious research has made use of the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) index to explore the association between shiftwork (SW) and insulin resistance (IR). However, the limitations of the HOMA-IR index restrict its use. This study aimed to investigate the relationship between SW and IR in professional drivers using four alternative non-insulin-based IR surrogate measures (NIRS), and to determine the predictors of elevated NIRS.MethodsA comparative cross-sectional study was conducted on professional drivers at four Egyptian companies, where 187 SW were compared to 193 dayworkers (DW). Measurements included: sociodemographic, work, and clinical characteristics. Laboratory and NIRS data included: triglyceride glucose (TyG), triglyceride glucose-body mass index (TyG-BMI), triglyceride to high density lipoprotein cholesterol (TG/HDL-C), and metabolic score of insulin resistance (METS-IR). Further assessments included insomnia severity index (ISI), and perceived stress scale (PSS-10).ResultsShiftwork-drivers showed significantly higher levels of NIRS compared to DW-drivers. Shiftwork was significantly associated with elevated TyG (OR: 5.04, 95% CI: 1.98–12.84), TyG-BMI (OR: 4.50, 95% CI: 2.45–8.26), and METS-IR (OR: 6.30, 95% CI: 2.72–14.58). Significant interactions between SW and insomnia or meal-timing habits existed, where SW-drivers with clinically significant insomnia had 11 times higher odds of elevated TyG compared to DW drivers without insomnia. Likewise, SW-drivers experiencing poor meal timing habits had 5.5- and 6.8-times higher odds of elevated TG/HDL-C and METS-IR, respectively, compared to DW divers without poor meal timing habits. Other significant predictors for elevated NIRS included: age, income, stress, overweight/obesity, and poor meal timing habits.ConclusionsThis study demonstrates a significant association between shiftwork and elevated insulin resistance in professional drivers. Insomnia and poor meal timing habits significantly increases the odds of insulin resistance among professional drivers, suggesting interventions targeting sleep quality, meal timing, and stress management.

UCP variants are linked to hypercholesterolemia and abdominal obesity in metabolically unhealthy women.

It has been reported that even with the same body mass index (BMI), there are subjects with metabolically healthy or unhealthy phenotype. The main determinants of the unhealthy phenotype are the type and distribution of fat, ectopic fat accumulation, genetics, and lifestyle factors. Uncoupling proteins (UCPs) disengage mitochondrial respiration from ATP synthesis and result in heat production, which in turn is related to energy expenditure and, thus, to fat mass accumulation. The association of the UCP1 -3826A/G (rs1800592), UCP2 Ala55Val (rs660339), and UCP3 -55C/T (rs1800849) variants with metabolic variables was evaluated according to metabolic phenotype in Mexican women. Women aged 18 to 65 years classified as normal weight (NW) or excessive weight (EW) according to their BMI (from 18.5 to <25 kg/m2 for NW, and from 25 to <40 kg/m2 for EW), were included. Participants were classified into two metabolic phenotypes: metabolically healthy or metabolically unhealthy (MH or MUH, respectively) based on ATP-III criteria and the homeostasis model assessment of insulin resistance (HOMA-IR). The genetic variants were determined by allelic discrimination using TaqMan® probes. In participants with the UCP1 -3826A/G variant, an increased risk of hypercholesterolemia was observed in those with the NW-MUH phenotype (OR=5.09, CI=1.03-25.12, p=0.017). The UCP2 Ala55Val variant in EW-MUH subjects was associated with higher abdominal obesity risk (OR=3.23, CI=1.21-8.60, p=0.019), while no associations were found with the UCP3 -55C/T variant. UCP1 and UCP2 variants are related with hypercholesterolemia and visceral fat accumulation in women with MUH phenotype.

Effect of Ficus pumila L. on Improving Insulin Secretory Capacity and Resistance in Elderly Patients Aged 80 Years Old or Older Who Develop Diabetes After COVID-19 Infection.

(1) Background: It has been reported that people affected by COVID-19, an infectious disease caused by SARS-CoV-2, suffer from various diseases, after infection. One of the most serious problems is the increased risk of developing diabetes after COVID-19 infection. However, a treatment for post-COVID-19 infection diabetes has not yet been established. In this study, we investigated the effects of Ficus pumila L. extract, which has traditionally been used to reduce blood glucose levels in Okinawa, on patients who developed diabetes after COVID-19 infection. (2) Methods: In total, 128 rehabilitation patients aged 80 years old or older who developed diabetes after COVID-19 infection were included. The HOMA-β (Homeostatic model assessment of β-cell function) and HOMA-IR (Homeostatic model assessment of insulin resistance) were assessed to evaluate the glucose tolerance. (3) Results: The HOMA-β decreased and HOMA-IR increased in patients who developed after diabetes after COVID-19 infection. Subsequently, 59 patients were given Ficus pumila L. extract and their HOMA-β and HOMA-IR improved after ingestion. On the other hand, the control group of patients who did not consume Ficus pumila L. showed no improvement in both HOMA-β and HOMA-IR. (4) Conclusions: Ficus pumila L. extract, ingested by patients who developed diabetes after COVID-19 infection, stimulated insulin secretion capacity and improved insulin resistance.

Genetically predicted brain cortical structure mediates the causality between insulin resistance and cognitive impairment

BackgroundInsulin resistance is tightly related to cognition; however, the causal association between them remains a matter of debate. Our investigation aims to establish the causal relationship and direction between insulin resistance and cognition, while also quantifying the mediating role of brain cortical structure in this association.MethodsThe publicly available data sources for insulin resistance (fasting insulin, homeostasis model assessment beta-cell function and homeostasis model assessment insulin resistance, proinsulin), brain cortical structure, and cognitive phenotypes (visual memory, reaction time) were obtained from the MAGIC, ENIGMA, and UK Biobank datasets, respectively. We first conducted a bidirectional two-sample Mendelian randomization (MR) analysis to examine the susceptibility of insulin resistance on cognitive phenotypes. Additionally, we applied a two-step MR to assess the mediating role of cortical surficial area and thickness in the pathway from insulin resistance to cognitive impairment. The primary Inverse-variance weighted, accompanied by robust sensitivity analysis, was implemented to explore and verify our findings. The reverse MR analysis was also performed to evaluate the causal effect of cognition on insulin resistance and brain cortical structure.ResultsThis study identified genetically determined elevated level of proinsulin increased reaction time (beta=0.03, 95% confidence interval [95%CI]=0.01 to 0.05, p=0.005), while decreasing the surface area of rostral middle frontal (beta=-49.28, 95%CI=-86.30 to -12.27, p=0.009). The surface area of the rostral middle frontal mediated 20.97% (95%CI=1.44% to 40.49%) of the total effect of proinsulin on reaction time. No evidence of heterogeneity, pleiotropy, or reverse causality was observed.ConclusionsBriefly, our study noticed that elevated level of insulin resistance adversely affected cognition, with a partial mediation effect through alterations in brain cortical structure.

Metabolic and inflammatory status in prepuberty and early adulthood for individuals with a history of extrauterine growth restriction: a cohort study

BackgroundPerinatal growth and nutrition have been shown to be determinants in the programming of different tissues, such as adipose tissue, predisposing individuals to metabolic alterations later in life. Previous studies have documented an increased risk of metabolic disturbances and low-grade inflammation in prepubertal children with a history of extrauterine growth restriction (EUGR). The aim of this study was to evaluate possible alterations resulting from impaired growth during early childhood and their impact on young adult health.MethodsThis is a longitudinal, descriptive and analytical study of a cohort with a history of EUGR recruited at prepubertal age and followed up for 10 years until the end of puberty. Anthropometric measurements, blood pressure, biochemical parameters related to lipid and carbohydrate metabolism and plasma adipokines and cytokines were analyzed.ResultsCompared with prepubertal children, young adults EUGR presented increased abdominal circumference percentiles. Moreover, insulin levels and the homeostatic model assessment for insulin resistance (HOMA-IR) index were higher in young adults, with a considerable proportion of participants (22%) becoming insulin-resistant after pubertal development. In contrast, arterial hypertension was observed in 36% of prepubertal children compared with 18% of postpubertal young adults. Lipid values were within normal ranges without differences. Adiponectin and leptin remained at similar levels in adulthood, with a decrease in resistin.ConclusionIndividuals with a history of EUGR have increased metabolic risk in adulthood, which emphasizes the importance of clinical follow-up from childhood to prevent the development of further future associated diseases.

Comparative effectiveness of massage combined with lifestyle intervention and lifestyle intervention alone for simple obesity: A systematic review and meta-analysis.

This study aimed to assess the comparative effectiveness of massage combined with lifestyle intervention and lifestyle intervention alone in patients with simple obesity. The PubMed, Embase, Cochrane Library, CNKI, VIP Database, and Wanfang Data were searched. Meta-analysis was conducted in accordance with the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Primary outcomes were body weight (BW) and body mass index (BMI). Secondary outcomes were waist circumference (WC), hip circumference (HC), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), fasting insulin (FINS), and homeostasis model assessment-insulin resistance (HOMA-IR) and adverse events. Thirteen randomized controlled trials were included. The meta-analysis showed that massage combined with lifestyle intervention significantly decreased BW (mean difference [MD]: -4.85; 95% confidence interval [CI]: -8.25 to -1.46; P = .005), BMI (MD: -2.65; 95% CI: -4.05 to -1.24; P = .0002), WC (MD: -3.63; 95% CI: -6.28 to -0.98; P = .007), TC (MD: -0.52; 95% CI: -0.84 to -0.20; P = .001), TG (MD: -0.23; 95% CI: -0.45 to -0.02; P = .003), LDL-C (MD: -0.48; 95% CI: -0.54 to -0.42; P < .00001), HDL-C (MD: -0.11; 95% CI: -0.17 to -0.05; P = .0004), FINS (MD: -1.64; 95% CI: -3.16 to -0.12; P = .03), and HOMA-IR (MD: -0.42; 95% CI: -0.65 to -0.18; P = .0005) compared with lifestyle intervention alone. In subgroup analyses, more obvious reduction in BMI (P = .02, I2 = 80.3%) for the children and adolescents subgroup, more obvious reduction in HC (P = .04, I2 = 76.1%) for the adults subgroup, more significant reduction in TC (P < .00001, I2 = 98.3%), LDL-C (P < .00001, I2 = 95.6%), and HDL-C (P < .0001, I2 = 94.1%) for intermittent treatment subgroup and more significant reduction in TC (P < .00001, I2 = 95.9%) and HDL-C (P < .0001, I2 = 94.1%) for treatment times ≤30 subgroup were detected. Compared with lifestyle intervention alone, massage combined with lifestyle intervention significantly decreased BW, BMI, WC, TC, TG, LDL-C, FINS, and HOMA-IR, but produced less effect in increasing HDL-C. And different ages, treatment intervals, and treatment times can all affect treatment outcomes.

Quinoa is more effective than other whole grains in the management of impaired glucose tolerance: a randomized controlled trial.

The purpose of this study was to compare the effects of quinoa versus multigrain supplementation on glycemia and lipid metabolism among individuals with impaired glucose tolerance (IGT). In total, 207 participants diagnosed with IGT were randomly assigned to the quinoa group (QG; 100 g day-1, replacing about half of the total daily staple food), multiple whole grain group (WGG; 100 g day-1), or control group (CG) and followed for one year. Biomarkers were measured before and after the intervention. At the efficacy endpoint, the quinoa group (QG) demonstrated significantly longer time in range (TIR) and normal glucose tolerance (NGT) conversion rate, along with lower rates of 2-hour postprandial glucose (2hPG), fasting insulin (FINS), homeostatic model assessment of insulin resistance (HOMA-IR), 14-day mean blood glucose (14dMBG), and diabetes mellitus development compared to those of the multigrain and control groups (P < 0.05). Significant improvements in glycated hemoglobin (HbA1c) were also found in both the quinoa and multigrain groups compared to the control group (P < 0.05). No significant difference in glycemic variability (CV) was observed between the quinoa and control groups, while a significant difference was observed between the quinoa and multigrain groups (P < 0.05). These results suggest that quinoa consumption is significantly more effective than a multiple whole-grain diet in controlling IGT by reducing postprandial glucose and HbA1c levels, improving insulin resistance, and enhancing lipid profiles, making it a superior dietary choice for managing IGT.