Homeostasis Model Assessment Research Articles

Swimming training promotes angiogenesis of endothelial progenitor cells by upregulating IGF1 expression and activating the PI3K/AKT pathway in type 2 diabetic rats.

The present study aimed to investigate the effect of swimming training on the angiogenesis of endothelial progenitor cells (EPCs) in type 2 diabetes mellitus (T2DM) rats by upregulating the insulin‑like growth factor 1 (IGF1) expression and to reveal its potential mechanism of action. Male Sprague‑Dawley rats were divided into the Control, Model, Model train, Model train + short interfering (si)‑NC and Model train + si‑IGF1 groups. Serum glucose levels were measured using the oral glucose tolerance test. EPCs were isolated from the bone marrow cavity and identified through morphological observation and immunofluorescence staining. The expression of IGF‑1 mRNA in rat serum and EPCs was analyzed by reverse transcription‑quantitative PCR. The fasting insulin levels in serum were assessed by ELISA. Cell Counting Kit‑8, scratch assay and tube formation assay were used to determine the cell viability, migration and tube formation of rat EPCs, and western blotting was employed to measure the expression levels of IGF1, phosphoinositide 3‑kinase (PI3K), phosphorylated‑PI3K, protein kinase B (AKT) and phosphorylated‑AKT. The present study demonstrated that swimming training significantly decreased the glucose levels and homeostatic model assessment of insulin resistance scores, but increased the fasting insulin levels and IGF1 mRNA expression. Microscopic observation and immunofluorescence identification suggested that EPCs were successfully isolated. In addition, swimming training markedly elevated the levels of IGF1 and promoted cell viability, migration and tube formation in rat EPCs. Furthermore, IGF1 knockdown experiments indicated that swimming training might play a regulatory role by elevating the IGF1 expression to activate the PI3K/AKT pathway. Overall, swimming training promoted the angiogenesis of EPCs in T2DM rats and its potential mechanism may be related to the upregulation of IGF1 expression and the activation of the PI3K/AKT pathway.

Atractylodes Lancea and Its Constituent, Atractylodin, Ameliorates Metabolic Dysfunction-Associated Steatotic Liver Disease via AMPK Activation.

Metabolic dysfunction-associated steatotic liver disease (MASLD), which encompasses a spectrum of conditions ranging from simple steatosis to hepatocellular carcinoma, is a growing global health concern associated with insulin resistance. Since there are limited treatment options for MASLD, this study investigated the therapeutic potential of Atractylodes lancea, a traditional herbal remedy for digestive disorders in East Asia, and its principal component, atractylodin, in treating MASLD. Following 8 weeks of high-fat diet (HFD) feeding, mice received oral doses of 30, 60, or 120 mg/kg of Atractylodes lancea. In HFD-fed mice, Atractylodes lancea treatment reduced the body weight; serum triglyceride, total cholesterol, and alanine aminotransferase levels; and hepatic lipid content. Furthermore, Atractylodes lancea significantly ameliorated fasting serum glucose, fasting serum insulin, and homeostatic model assessment of insulin resistance levels in response to HFD. Additionally, a glucose tolerance test demonstrated improved glucose homeostasis. Treatment with 5 or 10 mg/kg atractylodin also resulted in anti-obesity, anti-steatosis, and glucose-lowering effects. Atractylodin treatment resulted in the downregulation of key lipogenic genes (Srebf1, Fasn, Scd2, and Dgat2) and the upregulation of genes regulated by peroxisome proliferator-activated receptor-α. Notably, the molecular docking model suggested a robust binding affinity between atractylodin and AMP-activated protein kinase (AMPK). Atractylodin activated AMPK, which contributed to SREBP1c regulation. In conclusion, our results revealed that Atractylodes lancea and atractylodin activated the AMPK signaling pathway, leading to improvements in HFD-induced obesity, fatty liver, and glucose intolerance. This study suggests that the phytochemical, atractylodin, can be a treatment option for MASLD.

Constitutive Pleiotrophin Deletion Results in a Phenotype with an Altered Pancreatic Morphology and Function in Old Mice.

Pleiotrophin (PTN) is crucial for embryonic development and pancreas organogenesis as it regulates metainflammation, metabolic homeostasis, thermogenesis, and glucose tolerance. Pleiotrophin deletion is associated with a lipodystrophic phenotype in which adipose tissue plasticity is altered in late life. This study explored the impact of pleiotrophin deletion on pancreatic morphology and function in later life. We analyzed glucose tolerance and circulating parameters on female wild-type (Ptn+/+) and knock-out (Ptn-/-) mice. At 9 and 15 months, we conducted morphometric analyses of pancreatic islets and evaluated the levels of insulin, glucagon, somatostatin, glucose transporter 2 (GLUT2), vesicle-associated membrane protein 2 (VAMP2), and synaptosome-associated protein 25 (SNAP25) via immunofluorescence. The effect of PTN on glucose-stimulated insulin secretion (GSIS) was evaluated in INS1E cells and isolated islets. Ptn-/- mice showed hyperinsulinemia, impaired glucose tolerance, and increased homeostatic model assessment for insulin resistance (HOMA-IR) with age. While Ptn+/+ islets enlarge with age, in Ptn-/- mice, the median size decreased, and insulin content increased. Vesicle transport and exocytosis proteins were significantly increased in 9-month-old Ptn-/- islets. Islets from Ptn-/- mice showed impaired GSIS and decreased cell membrane localization of GLUT2 whereas, PTN increased GSIS in INS1E cells. Ptn deletion accelerated age-related changes in the endocrine pancreas, affecting islet number and size, and altering VAMP2 and SNAP25 levels and GLUT2 localization leading to impaired GSIS and insulin accumulation in islets.

Copper biomarkers and their relationship with parameters of insulin resistance in obese women.

Some studies have demonstrated the involvement of high concentrations of copper in the manifestation of insulin resistance in individuals with obesity. The objective of this study was to evaluate the copper nutritional status and its relationship with parameters of glycemic control in women with obesity. An observational case-control clinical study involving 203 women aged between 20 and 50years, divided into two groups: obese (n = 84) and eutrophic (n = 119). Body weight, height and waist, hip and neck circumferences, dietary copper intake, copper biomarkers, determine ceruloplasmin activity and glycemic control parameters were measured. It was observed that women with obesity had higher copper concentrations in plasma and lower concentrations in erythrocytes when compared to the control group. Analysis of glycemic control parameters revealed a statistically significant difference in fasting blood glucose (p < 0.05) between groups. The study identified a significant positive correlation between plasma copper and fasting insulin values and the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) index (p < 0.05). The results of this study demonstrate that obese women have high copper concentrations in plasma and lower concentrations in erythrocytes. Furthermore, the significant positive correlation between plasma copper and fasting insulin and HOMA-IR index suggests the influence of this mineral on glycemic control parameters in obese women.

Association between dynapenic obesity and risk of cardiovascular disease: The Hisayama study.

Dynapenic obesity is a condition characterized by high adiposity levels combined with muscle dysfunction. Although high adiposity and muscle loss/dysfunction are thought to synergistically increase the risk of cardiovascular disease (CVD), few studies have addressed the association between dynapenic and sarcopenic obesity and CVD. We aimed to investigate the association of dynapenic obesity with incident CVD events using the data from a population-based prospective longitudinal study in Japan. A total of 2490 community-dwelling Japanese aged 40-79years (42.5% males, mean age 57.7±10.6years) without a history of CVD were followed up for a median of 24years. Handgrip strength was classified as low, medium, or high by age- and sex-specific tertiles. Body mass index (BMI) levels were categorized as lean (<18.5kg/m2), normal (18.5-24.9kg/m2), or obese (≥25.0kg/m2). Dynapenic obesity was defined as having both low handgrip strength and obesity. The outcomes were defined as the first-ever development of CVD (defined as stroke or coronary heart disease). The hazard ratios (HRs) and their 95% confidence intervals (CIs) for the development of CVD were estimated using a Cox proportional hazards model, in which participants with high handgrip strength and normal BMI were used as a reference group. Mediation analyses used serum high-sensitivity C-reactive protein (hs-CRP) and homeostatic model assessment for insulin resistance (HOMA-IR) as mediators. During the follow-up period, 482 participants developed CVD events (324 cases of stroke and 209 of coronary heart disease). The multivariable-adjusted risk of CVD increased significantly among participants with dynapenic obesity compared with the reference group (HR 1.49, 95% CI 1.03-2.17). An analysis by age groups showed a further increase in the risk of CVD among participants with dynapenic obesity aged less than 65years (HR 1.66, 95% CI 1.04-2.65). In mediation analyses for participants aged less than 65years, serum hs-CRP was shown to be a significant mediator explaining 13.8% of the association between dynapenic obesity and the development of CVD, while HOMA-IR explained 12.2% of this relationship. Dynapenic obesity was a significant risk factor for the development of CVD in a general Japanese population. This association was more pronounced among those aged <65years. Inflammation, and possibly glucose metabolism, might partly mediate this association. Our findings suggest that preventing muscle dysfunction as well as appropriate weight control, especially in middle-age, are important for preventing the development of CVD.

Clinical significances of circulating serum fetuin-A, netrin-1, and ɑ-hydroxybutyrate levels in type 2 diabetes mellitus patients with and without hypertension

Background &amp; Objective: Type 2 diabetes (T2D) is a rising global health issue, with biomarkers such as fetuin-A (Fet-A), netrin-1 (NTN-1), and alpha-hydroxybutyrate (α-HB) showing potential for early diagnosis and management. These biomarkers can help predict T2D risk and understand insulin resistance (IR), emphasizing the need for further research. The current investigation evaluated the effectiveness of Fet-A, NTN-1, and, α-HB as novel biomarkers to diagnose T2D with hypertension. Methodology: A cross-sectional study was conducted from August to December 2023, involved 60 diabetic participants, which were divided into two groups: T2D without hypertension and T2D with hypertension. A third group consisted of 30 healthy controls (HC) for comparison. Serum samples were analyzed for fasting blood glucose (FBG) using the Roche/Cobas c111 system, as well as insulin, Fet-A, NTN-1, and α-HB levels using kits for the enzyme-linked immune-sorbent assay (ELISA). Descriptive statistics were used in the statistical package for social sciences (SPSS) for data analysis. Results: The study found significantly elevated Fet-A, NTN-1, and α-HB levels in T2D patients compared to HC, with no significant differences between T2D subgroups. Fetuin-A and α-HB showed non-significant correlations with FBG and homeostatic model assessment of IR (HOMA-IR) across all groups. NTN-1 positively correlated with FBG and HOMA-IR in T2D patients with hypertension. Conclusions: Elevated levels of fetuin-A and netrin-1, regardless of the presence of hypertension, are suggested by the study as possible biomarkers for the diagnosis of T2D. Netrin-1's significant correlation with HOMA-IR in hypertensive T2D patients underscores its utility in assessing insulin resistance severity. Although alpha-hydroxybutyrate levels were higher in T2D patients, their non-significant correlation with FBG and HOMA-IR requires further research. These biomarkers could aid in early diagnosis and disease monitoring for T2D management. Abbreviations: α-KB - α-ketobutyrate; ELISA - enzyme linked immune-sorbent assay; FA - fatty acids; FBG - fasting blood glucose; Fet-A - fetuin-A; HOMA-IR - homeostatic model assessment of IR; IR - insulin resistance; NAD - nicotinamide adenine dinucleotide; NADH - nicotinamide adenine dinucleotide hydrogen; ng - nanograms; NTN-1 - netrin-1; PB - peripheral blood; pg - picogram; SPSS - Statistical Package for Social Sciences; T2D - Type-2 diabetes mellitus; α-HB - alpha-hydroxybutyrate Keywords: Diabetes, Fetuin-A, Netrin-1, α-HB, HOMA-IR. Citation: Sfayyih HS, Jewad AM, Khudhair HAA. Clinical significance of circulating serum fetuin-A, netrin-1, and ɑ-hydroxybutyrate levels in type-2 diabetes mellitus patients with and without hypertension. Anaesth. pain intensive care 2024;28(5):883−893; DOI: 10.35975/apic.v28i5.2569 Received: Jul 22, 2024; Reviewed: August 10, 2024; Accepted: August 15, 2024

Exploring the heterogeneity of hepatic and pancreatic fat deposition in obesity: implications for metabolic health.

This retrospective observational study investigates the heterogeneity of hepatic and pancreatic fat deposition and its implications for metabolic health in individuals with obesity. A total of 706 patients with obesity underwent an MRI to quantify liver and pancreatic fat. Patients were classified into four groups based on fat deposition: no fat (None), fatty pancreas only (NAFPD), fatty liver only (NAFLD), and both conditions (NAFLD+NAFPD). Biochemical profiles, insulin resistance (Homeostatic Model Assessment for Insulin Resistance, HOMA-IR), and β-cell function were analyzed. A series of multiple linear regressions were used to investigate the independent effects of characteristics on glucose, insulin, and C-peptide at 0h. Another multiple linear regression was performed to evaluate the effects of basic characteristics on average liver fat, mean pancreatic fat, and visceral fat. The majority (76.63%) exhibited both NAFLD and NAFPD, highlighting the heterogeneity of fat deposition among individuals with obesity. Groups with fatty liver displayed significantly higher fasting glucose, insulin, C-peptide, and HOMA-IR levels than those without fatty liver (P < 0.01). Fatty pancreas alone did not significantly influence these metabolic parameters (P > 0.05). This underscores the greater metabolic impact of hepatic fat compared to pancreatic fat. The study confirms the complex heterogeneity of fat deposition in obesity, with the fatty liver being a more influential factor in metabolic disturbances than the fatty pancreas. The prevalent co-occurrence of NAFLD and NAFPD in this population underscores the need for targeted management strategies focusing on hepatic fat reduction to mitigate metabolic risk.

Insulin Resistance after Fontan Palliation.

Patients with a single ventricle heart who had Fontan palliation (S/P Fontan) are at increased risk for acquired morbidity. Insulin resistance (IR) is a predictor of cardiac morbidity and mortality. A single-center, cross-sectional study using S/P Fontan and controls was designed to assess IR S/P Fontan. Group comparisons were made in IR via the Quantitative Insulin Index (QUICKI) and the natural log-transformed homeostasis model assessment, ln (HOMA-IR), without/with adjusting for age. A total of 89 patients (59 Fontan and 30 controls) were included. Fontan patients showed a significant decrease in QUICKI (0.34 ± 0.03 vs 0.37 ± 0.02) and an elevation of ln (HOMA-IR) (0.82 ± 0.62 vs 0.24 ± 0.44) compared to controls (both p < 0.0001); this remained significant even adjusting for age. With older age, there was a significant, progressive decrease in QUICKI (p = 0.01) and an increase in ln (HOMA-IR) (p = 0.02) S/P Fontan. Analysis excluding Fontan patients with obesity still showed a significant reduction of QUICKI and an elevation of ln (HOMA-IR) in Fontan patients compared to controls when adjusting for age (both p < 0.05). Using QUICKI, IR was present in 41 (69.5%) Fontan patients vs. 3 (10%) controls (p < 0.0001) and using HOMA-IR, IR was present in 32 (54.2%) vs 5 (16.7%) controls (p = 0.001). Fontan patients had significantly more IR compared to controls and the prevalence of IR increases with age. Since IR is known to correlate with long-term morbidity and mortality and can be ameliorated by therapies, we believe it is critical that IR be identified as early as possible in Fontan patients.

7350 Association between thyroid function and insulin resistance indices in Korean adolescents: Findings from the 2014-2015 KNHANES

Abstract Disclosure: E. Mun: None. H. Lee: None. J. Choi: None. R. Lee: None. K. Kim: None. H. Kim: None. Purpose: Obesity and diabetes are rising concerns among adolescents. There are several studies regarding to the association between thyroid function and IR. However, there are limited studies focus on adolescents. Furthermore, there is a lack of studies evaluating various IR indices. We investigated the association between thyroid function and insulin resistance indices in adolescents with normal thyroid function. Methods: This cross-sectional study included 465 adolescents (aged 12-18, 255 boys, 210 girls) based on data from the Korea National Health and Nutritional Examination Survey2014-2015. Thyroid function was assessed using serum thyrotropin (TSH) and free thyroxine (fT4), while IR was estimated using the homeostasis model assessment of insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), glucose/insulin ratio (GIR), TyG (triglyceride-glucose index), and TG/HDL. Multiple linear regression analyzed the relationship between thyroid function and IR, stratified by sex. Nonlinearity was assessed through a restricted cubic spline model. Results: The mean TSH (uIU/mL) and fT4 (ng/dL) were 2.70 and 1.29, respectively. Boys had higher TSH (2.86 vs. 2.52, p = 0.013) and fT4 (1.33 vs. 1.24, p &amp;lt; 0.001) than girls, with significant gender differences. In girls, fT4 negatively correlated with HOMA-IR and positively with GIR. No significant relationship was found between thyroid function and IR in boys. When analyzed stratified by level of obesity, the association between IR and thyroid function was clear in the overweight/obese group in both sexes. Overweight and obese groups showed relationships between fT4 and HOMA-IR (β = 0.08, p = 0.04 in boys; β = -0.12, p &amp;lt; 0.01 in girls) and QUICKI (β = -4.14, p = 0.03 in boys; β = 6.60, p &amp;lt; 0.01 in girls). TSH correlated with TyG (β = 1.01, p = 0.04 in boys; β = 1.38, p = 0.01 in girls). In girls, fT4 was also related to TG/HDL (β = -0.06, p &amp;lt; 0.05) and GIR (β = 0.14, p &amp;lt; 0.01). Nonlinear analysis found no significant relationship between thyroid function and IR. Conclusion: The relationship between thyroid function and IR was more pronounced in the overweight and obese groups. Our study suggests that the correlation between thyroid function and insulin resistance in adolescents may vary based on gender and IR indices. Presentation: 6/1/2024

5124 Increased Copeptin May Reflect Vasopressin-Related Metabolic Changes After Bariatric Surgery

Abstract Disclosure: F. Galbiati: None. A. Aulinas Maso: None. I. Becetti: None. M. Lauze: None. V. Singhal: None. E.A. Lawson: Research Investigator; Self; received research funding and study drug from Tonix Pharmaceuticals. M. Bredella: None. M. Bredella: None. M. Misra: Advisory Board Member; Self; key opinion leader for Lumos Pharma. Consulting Fee; Self; Up To Date, Receives royalties. Objective: Vasopressin (AVP) is a neurohormone that decreases fat mass, promotes muscle regeneration, improves glucose homeostasis, and protects against hypoglycemia in animals and humans. Copeptin, a stable cleavage product of AVP, is positively associated with body mass index (BMI), insulin resistance, and metabolic syndrome in adults, suggesting an adaptive increase in AVP to counteract metabolic disruption. Similarly, copeptin was positively correlated with BMI in children. Metabolic and bariatric surgery (MBS) is highly effective at reducing metabolic complications of obesity, and underlying mechanisms may provide insights into novel therapeutics for obesity management. No study has investigated copeptin pre- and post-MBS in humans. We hypothesized that after MBS, (1) copeptin would increase and (2) increased copeptin would be associated with improved metabolic parameters. Methods: Longitudinal study in 64 adolescents and young adults (78% females; age [mean±SD] 18.7±2.8 years) with obesity (BMI 45.6±6.8 kg/m2). 34 underwent MBS (sleeve gastrectomy or Roux-en-Y gastric bypass) and 30 underwent non-surgical (NS) lifestyle management. We measured fasting circulating copeptin, %fat, and lean mass by dual-energy X-ray absorptiometry, hemoglobin A1c (HbA1c), and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) at baseline and 12 months. Results: Groups were similar for age, sex, race, and pubertal stage. Baseline BMI and %fat were higher in MBS (p≤.012). Baseline copeptin, %lean mass, HbA1c, and HOMA-IR did not differ across groups (p≥.103). MBS vs NS 12-month changes were [median(IQR)]: BMI -29.0 (-33.7, -16.5)% and 0.54 (-3.10, +4.37)%; %fat -8.03 (-13.33, -4.25) and -0.68 (-2.92, 0.64); %lean mass 7.73 (3.45, 12.38) and 0.83 (-.58, 2.73); HbA1c -0.40 (-0.52, -0.20) and -0.10 (-0.20, -0.02); HOMA-IR (mean±SD) -2.47±2.17 and 0.76±2.42 (ps≤.001). Baseline copeptin was correlated negatively with %fat (rho=-.25; p=.045), and positively with %lean mass (trend-level rho=.25, p=0.051). Copeptin increased in the MBS group and decreased in the NS group (time-x;-treatment effect: p=.017). Overall, copeptin change was correlated negatively with %fat change (rho=-.29; p=.025) and positively with %lean mass change (trend-level rho=0.24, p=.070). Copeptin change was positively correlated with changes in %lean mass (rho=.37, p=.045), HbA1c (rho=.46; p=.010), and HOMA-IR (rho=.53; p=.004), only after MBS. Conclusion: Overall, increase in copeptin over 12 months was associated with improved body composition, suggesting that increased AVP following MBS may contribute to its associated metabolic improvements. However, within the MBS group, improved glucose homeostasis was associated with reductions in copeptin, suggesting a possible protective mechanism against post-bariatric hypoglycemia. Presentation: 6/2/2024

The endocrine manifestations of adults with spinal muscular atrophy.

Changes in body composition in patients with spinal muscular atrophy (SMA) can cause endocrine abnormalities that are insufficiently studied in adults. We aimed to assess the endocrine profile in a cohort of adults with SMA. Second, we compared body composition and endocrine profiles between nonambulatory and ambulatory patients and between different types of SMA. The cross-sectional study included 29 SMA patients (18 [62.1%] males and 11 [37.9%] females) of median age 44 (IQR 30-51.5) years with type 2, 3, or 4. Body composition was measured by bioimpedance. Morning blood samples were drawn for glycated hemoglobin (HbA1c), lipid profile, testosterone, cortisol, and insulin-like growth factor-1 (IGF-1). Blood glucose, insulin, and beta-hydroxybutyrate (BHB) were measured during a 75 g oral glucose tolerance test. The homeostatic model assessment for insulin resistance index was calculated. In total, 75.9% of patients had increased fat mass (FM), with 51.7% having an increase despite normal body mass index. Ambulation was the most important discriminating factor of body composition. 93.1% of patients had metabolic abnormalities, including hyperglycemia, insulin resistance, and dyslipidemia. Increased BHB, a marker of ketosis, was present in more than a third of patients. Functional hypogonadism was present in half of male patients. Testosterone and IGF-1 negatively correlated with FM. Adult patients with SMA had abnormal body composition and highly prevalent metabolic disturbances that might increase cardiometabolic risk. Because treatments have modified the course of SMA, it is important to investigate whether these observations translate into clinically relevant outcomes.

Subclinical Hyperthyroidism Enhances Gonadotropin-Lowering Effects of Metformin in Postmenopausal Women.

Metformin treatment decreases elevated concentrations of anterior pituitary hormones. The aim of this prospective, cohort study was to investigate whether hyperthyroidism modulates the impact of metformin on gonadotroph secretory function. The study population included 48 postmenopausal women with untreated type 2 diabetes or prediabetes, 24 of whom had coexisting grade 1 subclinical hyperthyroidism. Both groups were matched for age, insulin sensitivity, and gonadotropin levels. Over the entire study period, all participants were treated with metformin (2.55-3 g daily). Plasma glucose, insulin, thyroid-stimulating hormone (TSH), total and free thyroid hormones, follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, prolactin, adrenocorticotropic hormone (ACTH), and insulin-like growth factor-1 (IGF-1) were assayed at entry and 6 months later. At baseline, the study groups differed in levels of TSH and thyroid hormones but not in body mass index, blood pressure, glucose homeostasis markers (fasting glucose, homeostatic model assessment 1 of insulin resistance ratio [HOMA1-IR], and glycated hemoglobin [HbA1c]), and the remaining hormones. There were no differences between both groups in the degree of reduction in plasma glucose and HbA1c in response to metformin treatment. Although metformin decreased HOMA1-IR in both groups, this effect was stronger in women with hyperthyroidism than with normal thyroid function (-50 ± 20% vs -30 ± 15%). Similar relationships were observed for FSH (-43 ± 21% vs -21 ± 12%). Only in hyperthyroid women did the drug reduce LH concentration (by 35 ± 17%). Metformin did not affect circulating levels of TSH, total and free thyroxine, total and free triiodothyronine, estradiol, prolactin, ACTH, and IGF-1. The obtained results indicate that hyperthyroidism enhances the gonadotropin-lowering effects of metformin, as well as the fact that this agent has a neutral effect on the hypothalamic-pituitary-thyroid axis in case of its overactivity.

The association of plasma asprosin with anthropometric and metabolic parameters in Korean children and adolescents.

This study aimed to determine the correlation of plasma asprosin with anthropometric and metabolic parameters in Korean children and adolescents. This single-center study included 109 Korean children and adolescents: 62 (56.9%) obese participants with a body mass index (BMI) ≥95th percentile and 47 (43.1%) healthy controls with BMI between the 15th and 85th percentile. Metabolic parameters were measured, including fasting blood glucose, fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR), triglyceride and glucose (TyG) index, and lipid profiles. Plasma asprosin levels were higher in the obese group than in the control group (mean 87.0 vs. 69.3 ng/mL; p = 0.001) and in the IR group than in the non-IR group (mean 98.6 vs. 70.2 ng/mL; p < 0.001). Plasma asprosin levels were not associated with sex or pubertal stage. Plasma asprosin levels were positively correlated with BMI SDS (r = 0.34; p = 0.002), glycated hemoglobin (HbA1c) (r = 0.25; p = 0.02), glucose (r = 0.33; p = 0.002), insulin (r = 0.44; p < 0.001), HOMA-IR (r = 0.47; p < 0.001), triglyceride (TG) (r = 0.33; p = 0.003), high-density lipoprotein (HDL) cholesterol (r = -0.29; p = 0.008), and TyG index (r = 0.38; p < 0.001). Multiple linear regression analysis indicated that plasma asprosin levels were independently associated with HOMA-IR (p < 0.001) and TG/HDL cholesterol ratio (p < 0.001). This study demonstrated an association between plasma asprosin levels and obesity and insulin resistance in Korean children and adolescents.

Insulin resistance reduction, intermittent fasting, and human growth hormone: secondary analysis of a randomized trial

Intense intermittent fasting regimens safely reduce weight to a similar extent as caloric restriction. A previous trial reported low-frequency 26-week intermittent fasting reduced homeostatic model assessment of insulin resistance (HOMA-IR) without significant weight loss. During fasting, human growth hormone (HGH) increases substantially, but whether basal HGH modifies the effect of fasting on outcomes of repeated fasting is unknown. In a post hoc analysis of a randomized controlled trial (registration: clinicaltrials.gov, NCT02770313, May 12, 2016), subjects (N = 68) were adults ages 21–70 years with modest cholesterol elevation, ≥1 metabolic syndrome component, available HGH measurements, no chronic disease, and no statin or anti-diabetes medication. Randomization was 1:1 to intermittent fasting (24-hour, water-only, twice-per-week for 4 weeks, then once-per-week for 22 weeks) or 26-week ad libitum control. General linear modeling evaluated the interaction of trial arm with baseline HGH for HOMA-IR changes. Subjects with lower baseline HGH had 26-week HOMA-IR changes (p = 0.003) of −1.04 ± 0.99 for fasting versus 0.60 ± 1.04 for controls. Subjects with higher baseline HGH had HOMA-IR changes (p = 0.26) of −0.69 ± 0.75 (fasting) and −0.42 ± 0.92 (controls). The interaction of fasting with lower baseline HGH was significant (p-interaction=0.004). Results were similar for insulin and glucose. Weight loss at 26 weeks was not significantly different between fasting and controls (−1.74 ± 4.81 kg vs. 0.21 ± 3.50 kg, p = 0.08) and was not correlated with changes in HOMA-IR, insulin, glucose, and HGH. In conclusion, lower baseline HGH modified the effect of low-frequency water-only 24-hour fasting in profoundly reducing HOMA-IR over 26 weeks compared both to controls and to fasting subjects with higher baseline HGH.

Efficacy of vitamin D supplementation on glycaemic control in type 2 diabetes: An updated systematic review and meta-analysis of randomized controlled trials.

To assess the effects of vitamin D interventions on glycaemic control in subjects with type 2 diabetes (T2D). We searched PubMed, EMBASE, Web of Science and the Cochrane Library for relevant studies. Serum 25(OH)D, fasting blood glucose (FBG), HbA1c, fasting insulin and Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) were analysed. We identified 39 randomized controlled trials involving 2982 subjects. Results showed a significant decline in the vitamin D group, as shown by the FBG weighted mean difference (WMD; -0.49 [95% confidence interval {CI}: -0.69 to -0.28] mmol/L), HbA1c (WMD -0.30% [95% CI: -0.43 to -0.18]), HOMA-IR (WMD -0.39 [95% CI -0.64 to -0.14]) and insulin (WMD -1.31 [95% CI: -2.06 to -0.56] μIU/mL). Subgroup analyses indicated that the effects of vitamin D supplementation on glycaemic control depend on the dosage and duration of supplementation, baseline 25(OH)D levels and the body mass index of patients with T2D. Vitamin D supplementation can significantly reduce serum FBG, HbA1c, HOMA-IR and fasting insulin levels in T2D patients; the effects were especially prominent when vitamin D was given in a short-term, high dosage to patients with a vitamin D deficiency, who were overweight, or had an HbA1c of 8% or higher at baseline. Our study suggests that vitamin D supplements can be recommended as complementary treatment for T2D patients.

Metabolic profile and glycemic response in fully-grown sows born using assisted reproductive technologies

The aim of the present work was to gain insight into the metabolism of pigs derived from assisted reproductive technologies during their adulthood. Approximately 4h after feeding, a blood sample was taken from 3.5 year old sows born by artificial insemination (AI group, n = 7) and transfer of in vitro produced embryos (IVP group, n = 11) to determine the physiological concentrations of the main biomarkers of carbohydrates (glucose and lactate), proteins (albumin, creatinine and urea) and lipids (cholesterol and triglycerides). Four weeks later, an oral glucose tolerance test (OGTT; 1.75g glucose/kg body weight) was performed after an overnight fast and 1h of water withdrawal. Blood samples were obtained prior (T = 0 min; fasting conditions) and 15, 30, 45, 60, 90, 120, 150, 180, 210 and 240 min after glucose intake. At each time point, glycemia was measured immediately using glucometer test strips, and serum was collected to determine the above metabolites along with insulin and glucagon. After OGTT, the area under the curve (AUC) between sampling times and homeostasis model assessment of insulin resistance (HOMA) indices were calculated. Under physiological conditions, the concentration of metabolites studied was similar between AI and IVP sows. In both groups, fasting decreased cholesterol and increased triglycerides and urea (P < 0.001). However, creatinine and lactate were similar in both groups under physiological and fasting conditions. The expected increase in albuminemia and decrease in glycaemia after fasting was only observed in IVP sows. OGTT revealed a different glucose curve pattern (monophasic in AI and biphasic in IVP group), a lower mean concentration of cholesterol, glucose, lactate, triglycerides in IVP compared to AI pigs (P < 0.01), and a higher mean concentration of albumin, creatinine and insulin in IVP compared to AI group (P < 0.05). On the contrary, no differences were found between groups for mean serum glucagon and urea levels, nor for glucose homeostasis indices HOMA-IR and HOMA-%B. The AUC differed between groups at several time points with larger AUC for creatinine, and smaller AUC for glucose, glucagon, and triglycerides, in IVP pigs than in AI pigs at 180–210 min (P < 0.05). In conclusion, under physiological conditions the metabolic profile of fully-grown AI and IVP sows is similar and within normal ranges. Glucose challenge revealed differences in metabolic and insulin responses between groups but with normal glucose tolerance in both cases.

A-073 Is there a relationship of FIB 4 with weight and insulin resistance in subjects without type 2 diabetes and with normal transaminases?

Abstract Background Metabolic dysfunction-associated steatotic liver disease (MASLD) is a common hepatic disease, affecting 20-30% of the world's population, and is more frequent in subjects with cardiometabolic diseases. The Fibrosis-4 Index (FIB-4) is a non-invasive scoring system that helps estimate the risk of hepatic fibrosis in MASLD. It is based on age, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and platelets (PLT). MASLD is associated with high risk of insulin resistance (IR) and type 2 diabetes (DM2), and subjects with overweight or obesity are more likely to have both. In such cases the association of FIB-4 with IR and weight are evident. It is questioned whether, even in subjects without DM2 and with normal transaminases, FIB-4 could be associated with the body mass index (BMI) and the homeostasis model assessment of insulin resistance index HOMA-IR, which is the index usually used to assess IR. The objective of this study was to evaluate how FIB-4 would behave in subjects without DM2 and with normal transaminases and whether there was a correlation between FIB-4 with HOMA-IR and BMI in these subjects. Methods Authors studied the distribution of FIB-4 results and correlation of HOMA-IR and BMI with FIB-4 using the database of a clinical laboratory. We included patients aged 20-65 years, both gender, who measured fasting glucose and insulin, in the same visit, and transaminases and platelets within up to one year before or later. Were excluded hospitalized subjects, those using medications to treat DM2, dyslipidemia, subjects with blood glucose over 200 mg/dL, and AST and/or ALT above the reference range for gender and age. The methods and reference intervals were: transaminases: UVKinetic, AST &amp;lt; 40 U/L for men and &amp;lt; 32 U/L for women, ALT &amp;lt; 41 for men and &amp;lt; 33 for women; PLT: automated method, 150000-450000/µL. Glucose: hexokinase, 70 - 99 mg/dL; Insulin: electrochemiluminescence, 2-12 mcU/mL. HOMA-IR index was calculated using the equation: glucose (mg/dL) x insulin (mcIU/mL) / 405 and FIB-4 using the equation: age (years) × TGO (U/L) / [(platelets (µL) ÷1000) x √TGP (U/L))]. Shapiro Wilk test was performed to assess whether the analytes had normal distribution. To evaluate the correlation with HOMA-IR, Spearman's non-parametric correlation test was used. Results After applying the exclusion criteria and subtracting outliers 270,135 records were selected, 75% female, with 39,9 ± 10.1 years. As the parameters did not present Gaussian distribution, the results are shown in median and 25th and 75th percentiles: AST=18.9 (16-22); ALT=17.2 (13-23.3); PLT=266000 (229000-308000); glucose = 89.3 (84.2-95); insulin = 8.17 (5.52-12.8); HOMA-IR=1.81 (1.19-2.75); IMC=26.53 (23.80-29.91); FIB-4 = 0.65 (0.5 - 0.86). A weak and surprisingly negative correlation between HOMA-IR and BMI with FIB-4 was found. (HOMA-IR: r=- 0.2, p&amp;lt;0.001; BMI: r=- 0.1, p&amp;lt;0.01). Conclusions Our study showed that in a population with normal transaminases, FIB-4 had results compatible with low risk of fibrosis in subjects without DM2 even in cases with high HOMA-IR or BMI. The negative correlation was surprising and perhaps indicates that FIB-4 may not be a good predictor of liver fibrosis for this population profile.

Characteristics of High-Intensity Interval Training Influence Anthropometrics, Glycemic Control, and Cardiorespiratory Fitness in Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Exercise is a non-pharmacological intervention for type 2 diabetes mellitus (T2DM), including moderate-intensity continuous training (MICT) and high-intensity interval training (HIIT). Despite diverse exercise protocol variations, the impact of these variations in HIIT on T2DM anthropometrics, glycemic control, and cardiorespiratory fitness (CRF) remains unclear. The aim was to examine the influence of HIIT protocol characteristics on anthropometrics, glycemic control, and CRF in T2DM patients and compare it to control (without exercise) and MICT. This review is registered in PROSPERO (CRD42021281398) and follows Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The search, employing "high-intensity interval training" and "diabetes mellitus" in PubMed and Web of Science databases, with a "randomized controlled trial" filter, spanned articles up to January 2023. Of 190 records, 29 trials were included, categorized by HIIT interval duration, training volume, and intervention period. Long-duration, high-volume, and long-term HIIT yields superior outcomes compared to control conditions for body mass, waist circumference, fasting plasma glucose, Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), glycosylated hemoglobin (%HbA1c), and CRF. The findings favored HIIT over MICT for body mass in long-duration, high-volume, and short-term intervals (mean difference[MD] - 3.45, - 3.13, and - 5.42, respectively, all p < 0.05) and for CRF in long and medium work intervals and high volume (MD 1.91, 2.55, and 2.43, respectively, all p < 0.05), as well as in medium and long-term intervention (MD 2.66 and 2.21, respectively, all p < 0.05). Regardless of specific HIIT characteristics, no differences were found in the HIIT versus MICT comparison for glycemic control. Specific HIIT protocol characteristics influence changes in anthropometrics, glycemic control, and CRF compared to control groups. However, compared to MICT, only longer duration, higher volume, and short-term HIIT improved body mass, waist circumference, and CRF in individuals with T2DM.

Association between insulin resistance indices and kidney stones: results from the 2015-2018 National Health and Nutrition Examination Survey.

To explore the association between representative insulin resistance (IR) indices and the risk of kidney stone disease in an American adult population. The representative IR indices referred to metabolic score for IR (METS-IR), triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio, triglyceride glucose-body mass index (TyG-BMI), visceral adiposity index (VAI), and homeostatic model assessment of IR (HOMA-IR). We investigated adult participants who joined the 2015-2018 National Health and Nutrition Examination Survey (NHANES) and reported kidney stone histories. Weighted proportions, multivariable regression analysis, and restricted cubic splines were used to evaluate the associations between IR indices and kidney stones after their adjustment for gender, age, race, education, smoking status, alcohol drinking frequency, hypertension and diabetes status, physical activity level, water intake, and levels of calcium, cholesterol, and uric acid. A total of 19,225 participants were included. The weighted prevalence of kidney stone was 11.1%. A multivariable logistic regression model showed a dose-response relationship between the METS-IR and kidney stone [odds ratio (OR) = 1.02, 95% confidence interval (CI) (1.01, 1.04), p < 0.01]. A similar relationship was observed between the TyG-BMI and kidney stone after full adjustment [OR = 1.0, 95% CI (1.0, 1.01), p < 0.001]. Sex-stratified analyses revealed that the association between METS-IR and nephrolithiasis [OR = 1.03, 95% CI (1.01, 1.05), p < 0.01], and the association between TyG-BMI and nephrolithiasis [OR = 1.01, 95% CI (1.0, 1.01), p <0.001] was significant among the male participants in the fully adjusted model. Moreover, a significant association was found between the METS-IR levels and nephrolithiasis [OR = 1.03, 95% CI (1.01, 1.06), p < 0.01], and between the TyG-BMI levels and nephrolithiasis [OR = 1.01, 95% CI (1.0, 1.01), p < 0.05] among the diabetic participants after full adjustment. Furthermore, a potential nonlinear association was found between other IR indices (i.e., TG/HDL-C, VAI, and HOMA-IR) and the risk of kidney stone disease. Higher METS-IR and TyG-BMI levels were associated with a higher risk of nephrolithiasis. Future investigations are required to identify the role of IR in the progress of kidney stone formation and to propose prevention measures and health guidelines.

Efficacy of WeChat-Based Digital Intervention Versus Metformin in Women With Polycystic Ovary Syndrome: Randomized Controlled Trial.

The first-line treatment for polycystic ovary syndrome (PCOS) is lifestyle modification. However, it is currently unknown whether digital medicine can assist patients with PCOS in maintaining a healthy lifestyle while alleviating PCOS symptoms. This study aims to evaluate the efficacy of WeChat-based digital intervention versus metformin treatment in women with PCOS and insulin resistance. A total of 80 women with PCOS and insulin resistance were recruited from an endocrinology clinic and randomly assigned to receive either a WeChat-based digital intervention (n=40, 50%) or metformin (n=40, 50%) for 12 weeks. The WeChat-based digital intervention consisted of 3 modules; a coach assisted the patients in using the intervention. The primary outcome was the change in a homeostatic model assessment for insulin resistance. At baseline and after the 12-week intervention, anthropometric parameters, menstruation frequency, sex hormone levels, metabolic factors, and body fat distribution were measured in the clinic. Furthermore, self-assessed web-based questionnaires on diet, exercise, sleep, anxiety, and depression were obtained. A total of 72 participants completed the follow-up (for a 90% follow-up rate), including 35 of 40 (88%) participants from the digital intervention group and 37 of 40 (93%) participants from the metformin group. The homeostatic model assessment for insulin resistance in the digital intervention group was significantly improved after 12 weeks of treatment with a mean change of -0.93 (95% CI -1.64 to -0.23), but no statistical difference was observed between the groups (least squares mean difference -0.20; 95% CI -0.98 to 0.58; P=.62). Both digital intervention and metformin treatment significantly improved menstruation frequency (digital intervention: P<.001; metformin: P<.001) and reduced body weight (digital intervention: P<.001; metformin: P<.001) and total fat mass (digital intervention: P<.001; metformin: P<.001). Furthermore, the digital intervention had a significant advantage over metformin in improving waist circumference (least squares mean difference -1.84; 95% CI -3.44 to -0.24; P=.03), waist-to-hip ratio (least squares mean difference -0.02; 95% CI -0.03 to 0.00; P=.03), total fat mass (least squares mean difference -1.59; 95% CI -2.88 to -0.30; P=.02), and dehydroepiandrosterone sulfate (least squares mean difference -69.73; 95% CI -129.70 to -9.75; P=.02). In terms of safety, the main adverse events were sensations of hunger in the digital intervention group (2/40, 5%) and gastrointestinal adverse events in the metformin group (12/40, 30%). Our data suggest that digital intervention is an effective treatment option for patients with PCOS, with an efficacy comparable to that of metformin, and that it can also alleviate the negative effects of medications and make it easier and more efficient to adhere to lifestyle treatments. WeChat-based digital interventions have the potential to provide a new path for the improvement and health of women with PCOS in China. ClinicalTrials.gov NCT05386706; https://clinicaltrials.gov/study/NCT05386706.