Midlife insulin resistance, APOE genotype, and change in late-life brain beta-amyloid accumulation - A 5-year follow-up [11C]PIB-PET study.

We studied if midlife insulin resistance (IR) and APOE genotype would predict brain beta-amyloid (Aß) accumulation and Aß change in late-life in 5-year follow-up [11C]PIB-PET study. 43 dementia-free participants were scanned twice with [11C]PIB-PET in their late-life (mean age at follow-up 75.4 years). Participants were recruited from the Finnish Health2000 study according to their HOMA-IR values measured in midlife (mean age at midlife 55.4 years; IR+ group, HOMA-IR > 2.17; IR- group, HOMA-IR <1.25), and their APOEε4 genotype. At late-life follow-up, [11C]PIB-PET composite SUVr was significantly higher in IR+ group than IR- group (median 2.3 (interquartile range 1.7-3.3) vs. 1.7 (1.5-2.4), p = 0.03). There was no difference between IR- and IR+ groups in [11C]PIB-PET SUVr 5-year change, but the change was significantly higher in IR+/APOEε4+ group (median change 0.8 (0.60-1.0)) than in IR-/APOEε4- (0.28 (0.14-0.47), p = 0.02) and in IR+/APOEε4- group (0.24 (0.06-0.40), p = 0.046). These results suggest that APOEε4 carriers with midlife IR are at increased risk for late-life Aß accumulation.

Interpregnancy interval and early infant neurodevelopment: the role of maternal-fetal glucose metabolism.

BACKGROUND: Interpregnancy interval (IPI) is associated with a variety of adverse maternal and infant outcomes. However, reports of its associations with early infant neurodevelopment are limited and the mechanisms of this association have not been elucidated. Maternal-fetal glucose metabolism has been shown to be associated with infant neurodevelopmental. The objective of this study was to determine whether this metabolism plays a role in the relationship between IPI and neurodevelopment. METHODS: This prospective birth cohort study included 2599 mother-infant pairs. The IPI was calculated by subtracting the gestational age of the current pregnancy from the interval at the end of the previous pregnancy. Neurodevelopmental outcomes at 12 months in infants were assessed by the Ages and Stages Questionnaire Edition 3 (ASQ-3). Maternal fasting venous blood was collected at 24-28 weeks and cord blood was collected at delivery. The association between IPI and neurodevelopment was determined by logistic regression. Mediation and sensitivity analyses were also conducted. RESULTS: In our cohort, 14.0% had an IPI < 12 months. IPI < 12 months increased the failure of the communication domain, fine motor domain, and personal social domain of the ASQ (relative risks (RRs) with 95% confidence interval (CI): 1.73 [1.11,2.70]; 1.73 [1.10,2.72]; 1.51 [1.00,2.29]). Maternal homeostasis model assessment of insulin resistance (HOMA-IR) and cord blood C-peptide was significantly associated with failure in the communication domain [RRs with 95% CI: 1.15 (1.02, 1.31); 2.15 (1.26, 3.67)]. The proportion of the association between IPI and failure of the communication domain risk mediated by maternal HOMA-IR and cord blood C-peptide was 14.4%. CONCLUSIONS: IPI < 12 months was associated with failing the communication domain in infants. Maternal-fetal glucose metabolism abnormality may partially explain the risk of neurodevelopmental delay caused by short IPI.

Sex differences in the association between insulin resistance and non-fatal myocardial infarction across glycaemic states.

BACKGROUND: Females are generally less prone to cardiovascular (CV) events than males, but this protection is trumped by diabetes. The mechanism behind the increased relative risk in females with diabetes is not fully understood. Insulin resistance (IR) is suggested to be a more important contributor to CV morbidity in females than in males. We aim to investigate differences in the association between IR indexes (Homeostatic Model Assessment of IR - HOMA-IR, visceral adiposity index - VAI, and triglycerides/high-density lipoprotein-cholesterol - TG/HDL-C index), and a first non-fatal myocardial infarction (MI) across different glycaemic states. METHODS: IR indexes were calculated in a population with (n = 696) and without (n = 707) a first non-fatal MI, free from known diabetes. MI cases were investigated at least six weeks after the event. All participants were categorized by an oral glucose tolerance test as having normal glucose tolerance, impaired fasting glucose, impaired glucose tolerance, or newly diagnosed diabetes. Comparison of proportion of glycaemic states by sex was tested by chi-square test. The associations between sex, a first non-fatal MI, IR indexes, and traditional CV risk factors were analysed by multivariate logistic regression models. Continuous variables were logarithmically transformed. RESULTS: Of the total population 19% were females and 81% males, out of whom 47% and 50% had a first non-fatal MI, respectively. Compared with males, females were older, less often smokers, with lower body mass index and higher total cholesterol and high-density lipoprotein cholesterol levels. The proportion of glycaemic states did not differ between the sexes (p = 0.06). Females were less insulin resistant than males, especially among cases and with normal glucose tolerance. In logistic regression models adjusted for major CV risk factors including sex, the associations between VAI and TG/HDL-C index and a first non-fatal MI remained significant only in females (odds ratios and 95% confidence intervals: 1.7, 1.0-2.9, and 1.9, 1.1-3.4 respectively). CONCLUSIONS: These results support the assumption that IR indexes based on anthropometrics and lipid panel, i.e., VAI and TG/HDL-C, could be a better measure of IR and CV-predictor for non-fatal MI in females, even without glycaemic perturbations.

METS-IR/HOMA-IR and MAFLD in U.S. adults: dose-response correlation and the effect mediated by physical activity.

OBJECTIVES: Metabolic dysfunction-associated fatty liver disease (MAFLD), a globally prevalent disease, is closely linked to insulin resistance (IR). Physical activity (PA) is closely linked to both MAFLD and IR. We aim to explore the dose-response relationship between metabolic score for IR (METS-IR)/homeostasis model assessment of IR (HOMA-IR) and MAFLD, and investigate the relationship between PA, IR and MAFLD. METHODS: Participants from the NHANES study were included in this cross-section study. Logistic regression and the receiver operating characteristic were used to assess the predictive performance of METS-IR/HOMA-IR for MAFLD. Restrictive cubic splines were performed to visualize their dose-response relationship. Decision tree analysis was used to identify high-risk populations of MAFLD. PA's mediating effect in the association between METS-IR/HOMA-IR and MAFLD was also examined. RESULTS: Of all 1,313 participants, 693 had MAFLD (52.78%). There were a positive association between METS-IR (OR = 1.162, 95% CI = 1.126-1.199) and HOMA-IR (OR = 1.630, 95% CI = 1.431-1.856) and MAFLD risk. The AUCs of the METS-IR and HOMA-IR were 0.831 (0.809, 0.853) and 0.767 (0.741, 0.791), respectively, with significantly different predictive performance (P < 0.001). Adding METS-IR/HOMA-IR to the basic model greatly improved the statistical significance for MAFLD. Five high-risk subgroups were identified for MAFLD. PA mediated about 0.81% and 0.78% (indirect effect/total effect) in the association between METS-IR/HOMA-IR and MAFLD. CONCLUSIONS: MAFLD risk might be predicted by METS-IR/HOMA-IR, among which METS-IR performed better. And PA mediated the association between them. More attention should be paid to the therapeutic effect of lifestyle changes on MAFLD. HIGHLIGHTS: 1. Positive associations were found between METS-IR and HOMA-IR and MAFLD risk. 2. METS-IR has better predictive performance for MAFLD risk than HOMA-IR. 3.Two high-risk subgroups were identified for MAFLD by METS-IR: individuals with METS-IR ≥ 40; Hispanic black individuals with 34 ≤ METS-IR < 40 and aged ≥ 46. 4. In the significant association between METS-IR/HOMA-IR and MAFLD, about 0.81% and 0.78% (indirect effect/total effect), respectively, were mediated by physical activity.

The effect of psyllium on fasting blood sugar, HbA1c, HOMA IR, and insulin control: a GRADE-assessed systematic review and meta-analysis of randomized controlled trials.

There is equivocal evidence that psyllium can prevent or attenuate increases in fasting blood sugar. Therefore, this systematic review and meta-analysis sought to investigate the influence of psyllium on hemoglobin A1C (HbA1c), fasting blood sugar (FBS), insulin, and Homeostatic Model Assessment of Insulin Resistance (HOMA IR). We searched PubMed, ISI Web of Science (WOS), and Scopus for eligible publications, up to 15 July 2022, including randomized controlled trials (RCT) assessing the effect of psyllium on HbA1c, FBS, insulin, and HOMA IR levels in adults. Using a random effects model, we report the weighted mean differences (WMD) with 95% confidence intervals (CI). In this article, 19 RCT studies, consisting of 962 participants, were included. Psyllium significantly decreased FBS, HbA1c, and HOMA IR levels, but not insulin levels, as compared to placebo (FBS: WMD): -6.89; 95% CI: -10.62, -3.16; p < .001), HbA1c: (WMD: -0.75; 95% CI: -1.21, -0.29; p < .001), HOMA IR: (WMD: -1.17; 95% CI: -2.11, -0.23; p < .05), and insulin: (WMD: -2.08; 95% CI: -4.21, -0.035; p > .05)). Subgroup analyses illustrated differences in the effects of psyllium on FBS: dosages less than and more than 10 g/d showed significant differences (p value < 0.05). However, it was not significant in intervention durations less than 50 days (p value > 0.05). For HbA1c: psyllium consumption less than 10 g/d (p value > 0.05) was non-significant. For HOMA IR and insulin: no significant changes were noted with psyllium consumption less than vs. more than 10 g/d. In conclusion, we found that psyllium could significantly decrease FBS, HbA1c, and HOMA IR levels, but not insulin levels, as compared to placebo.

The impact of a culturally adapted lifestyle intervention on the glycaemic profile of mothers with GDM one year after delivery - a community-based, cluster randomized trial in Sri Lanka.

BACKGROUND: A woman with a history of GDM has a high risk of developing type two diabetes (T2DM) in her future life. Lifestyle modifications are known to attenuate the progression of GDM to T2DM. Therefore, the aim of this study was to assess the impact of a simple, cost effective, culturally acceptable lifestyle intervention programme on the trajectory towards T2DM in women with a history of GDM. METHODS: This cluster randomized trial was conducted in 100 postpartum women in three selected districts of Sri Lanka. The subjects were divided into intervention (n = 50) and control groups (n = 50) by cluster randomization method. A culturally adapted protocol (comprised of dietary and physical activity modifications) was administered to the intervention group. The glycemic profile was assessed using fasting and 2-hour post-OGTT plasma glucose and HbA1c, and insulin resistance by HOMA-IR at baseline and after one year of intervention. RESULTS: The mean age (SD) of the subjects in the intervention and control groups were 33.0 (5.1) and 34.3 (6.5) years respectively. All glycemic and insulin resistance parameters (i.e. Fasting plasma glucose- FPG, 2-hour post-OGTT plasma glucose, HbA1c and HOMA-ir) were comparable (p > 0.05) between the two groups at baseline. FPG, 2 h post OGTT, HbA1c and HOMA-ir values between intervention vs. control (p) at 12 months were 87.3 vs. 123.2 (< 0.01); 106.5 vs. 156.1 (0.01); 5.3 vs. 6.8 (< 0.01) and 0.9 vs. 2.3 (< 0.01) respectively. All glycemic parameters showed a significant reduction in the intervention group at 12 months compared to baseline. In contrast, the control group showed a significant increase in FPG, 2-hour post-OGTT plasma glucose and HbA1c at 12 months compared to baseline. In multiple linear regression model adjusted for age, parity and family history, the control group showed an approximately 33 times risk of developing insulin resistance compared to the intervention group. CONCLUSION: The culturally acceptable and individualized lifestyle intervention was able to produce remarkable reductions in glycaemic and insulin resistance parameters among postpartum women with a history of GDM. TRIAL REGISTRATION: Ethical clearance was obtained from the Ethics Review Committee of the University of Sri Jayewardenepura, Sri Lanka (ERC 52/14), Sri Lanka Clinical trial registration number Sri Lanka Clinical Trials Registry (SLCTR/2015/021 date 25.09.2015).

Association between exposure to outdoor artificial light at night during pregnancy and glucose homeostasis: A prospective cohort study.

BACKGROUND: Outdoor artificial light at night (ALAN) has been linked to an elevated risk of diabetes, but the available literature on the relationships between ALAN and glucose homeostasis in pregnancy is limited. METHODS: A prospective cohort study of 6730 pregnant women was conducted in Hefei, China. Outdoor ALAN exposure was estimated using satellite data with individual addresses at a spatial resolution of approximately 1 km, and the average ALAN intensity was calculated. Gestational diabetes mellitus (GDM) was diagnosed based on a standard 75-g oral glucose tolerance test. Multivariable linear regression and logistic regression were used to estimate the relationships between ALAN and glucose homeostasis. RESULTS: Outdoor ALAN was associated with elevated glucose homeostasis markers in the first trimester, but not GDM risk. An increase in the interquartile range of outdoor ALAN values was related to a 0.02 (95% confidence interval [CI]: 0.00, 0.03) mmol/L higher fasting plasma glucose, a 0.42 (95% CI: 0.30, 0.54) µU/mL increase in insulin and a 0.09 (95% CI: 0.07, 0.12) increase in homeostatic model assessment of insulin resistance (HOMA-IR) during the first trimester. Subgroup analyses showed that the associations between outdoor ALAN exposure and fasting plasma glucose, insulin, and HOMA-IR were more pronounced among pregnant women who conceived in summer and autumn. CONCLUSIONS: The results provided evidence that brighter outdoor ALAN in the first trimester was related to elevated glucose intolerance in pregnancy, especially in pregnant women conceived in summer and autumn, and effective strategies are needed to prevent and manage light pollution.

Association between birth weight and insulin resistance in US adolescents: A retrospective cohort study exploring the role of concurrent body mass index.

BACKGROUND AND AIMS: This study aimed to investigate the association between birth weight (BW) and abnormal HOMA-IR in US adolescents aged 12-15 years. The role of concurrent body mass index (BMI) in adolescence was also examined. METHODS AND RESULTS: This retrospective cohort study included 3429 participants from NHANES with data in 1999-2020. HOMA-IR ≥2.3 was considered abnormal. Participants were classified as low (LBW; <2.5 kg), normal (NBW; 2.5-4.0 kg), or high (HBW; >4.0 kg) BW. Logistic regression was used to explore the association between BW and HOMA-IR. Mediation analysis was used to examine whether BMI z-score in adolescence mediated the association between BW and HOMA-IR. Compared with those in NBW, the odds ratios (95 % CI) of abnormal HOMA-IR in LBW and HBW groups were 1.26 (0.99-1.60), and 0.62 (0.47-0.83) respectively. The association between BW and abnormal HOMA-IR was consistent in all subgroups with no significant interactions. Mediation analysis showed that BW is associated with lower risk of HOMA-IR directly, but with higher risk indirectly via BMI in adolescence. CONCLUSION: There was a negative linear relationship between BW and the prevalence of abnormal HOMA-IR in adolescents aged 12-15 independent of concurrent BMI. Children who were born with LBW but had high BMI in adolescence were of particularly higher risk of insulin resistance.

Impact of triglyceride-glucose index on intracoronary thrombus burden in ST-elevation myocardial infarction patients undergoing primary percutaneous coronary intervention.

BACKGROUND AND AIMS: We aimed to investigate the relationship between triglyceride glucose (TyG) index and intracoronary thrombus burden in patients with ST-elevation myocardial infarction (STEMI) who underwent primary percutaneous coronary intervention (PCI). METHODS AND RESULTS: A total of 468 consecutive patients who were admitted with STEMI and underwent primary PCI were included in the study. TyG index was calculated as ln [fasting triglycerides (mg/dL) × fasting plasma glucose (mg/dL)/2]. According to the angiographic reclassified thrombolysis in myocardial infarction (TIMI) thrombus grade, patients were divided into two groups as small thrombus burden (STB) with TIMI thrombus grade 0-3, and large thrombus burden (LTB) with TIMI thrombus grade 4-5. TyG index was significantly higher in the LTB group than in the STB group (9.11 ± 0.86 vs 8.89 ± 0.62; p = 0.002). In multivariate analysis, TyG index was found to be an independent predictor of LTB in STEMI patients who underwent primary PCI [OR (95 % CI): 1.470 (1.090-1.982), p = 0.012]. The area under the curve (AUC) of TyG index predicting LTB was 0.568 (95 % CI 0.506-0.631; p = 0.023), with the best cut-off value of 8.87. In the classification according to TyG index cut-off value, the frequency of LTB was found to be significantly higher in the high TyG index group than in the low TyG index group (33.6 % vs 21.2 %; p = 0.003). CONCLUSION: TyG index, a valid surrogate marker of insulin resistance, is an independent predictor of LTB in STEMI patients who underwent primary PCI and can be used as an indicator of increased intracoronary thrombus burden.

Effects of prenatal dexamethasone exposure on adult C57BL/6J mouse metabolism and oxidative stress.

Prenatal glucocorticoid exposure has been shown to alter hypothalamic-pituitary-adrenal axis function resulting in altered fetal development that can persist through adulthood. Fetal exposure to excess dexamethasone, a synthetic glucocorticoid, has been shown to alter adult behaviour and metabolism. This study investigated the effects prenatal dexamethasone exposure had on adult offspring cardiac and liver metabolism and oxidative stress. Pregnant C57BL/6 mice received a dose of 0.4 mg/kg dexamethasone on gestational days 15-17. Once pups were approximately 7 months old, glucose uptake was determined using positron emission tomography and insulin resistance (IR) was determined by homeostatic model assessment (HOMA) IR calculation. Oxidative stress was assessed by measuring 4-hydroxynonenal protein adduct formation and total reactive oxygen species. Female dexamethasone group had significantly increased glucose uptake when insulin stimulated compared to vehicle-treated mice. HOMA IR revealed no evidence of IR in either male or female offspring. There was also no change in oxidative stress markers in either cardiac or liver tissues of male or female offspring. These data suggest that prenatal dexamethasone exposure in male mice does not alter oxidative stress or metabolism. However, prenatal dexamethasone exposure increased glucocorticoids, cardiac glucose uptake, and pAkt signaling in female heart tissues in adult mice, suggesting there are sex differences in prenatal dexamethasone exposure.

Type IIx muscle fibers are related to poor body composition, glycemic and lipidemic blood profiles in young females: the protective role of type I and IIa muscle fibers.

PURPOSE: The aim of the present study was to investigate the association between muscle fiber composition, body composition, resting glycemic-lipidemic blood profiles, in apparently healthy, young, active females. METHODS: Thirty-four young healthy female volunteers were allocated into two groups, depending on their Vastus Lateralis type IIx muscle fibers percent cross-sectional area (%CSA; H: high type IIx %CSA; L: low type IIx %CSA). Body composition was determined via dual-energy X-ray absorptiometry. Venous blood samples were collected for the determination of resting serum glucose, Insulin, Apo-A1, HOMA-IR, triglycerides (TG), total cholesterol (TC), High-density lipoprotein (HDL-C), and Low-density lipoprotein (LDL-C) concentrations. Nutritional intake was also evaluated. RESULTS: Individuals of the H group have significantly higher body mass, body fat percentage-mass, and resting blood indices of glycemic and lipidemic profiles, compared to those of L group (p < 0.001). Increased type IIx and low type I, IIa muscle fibers %CSAs were linked with poorer body composition, glycemic and lipidemic blood profiles (r: - 0.722 to 0.740, p < 0.001). Linear regression analyses revealed that the impact of muscle fibers %CSA (B coefficients ranged between - 0.700 and 0.835) on the above parameters, was at least, of the same or even of greater magnitude as that of body composition and daily nutritional intake (B: - 0.700 to 0.666). CONCLUSION: Increased type IIx and low Type I, IIa %CSAs are associated with poorer body composition and glycemic-lipidemic profiles in young healthy females. The contribution of the muscle fiber %CSA on health status seems to be comparable to that of nutrition and body composition.

Associations of sedentary behavior and screen time with biomarkers of inflammation and insulin resistance.

Sedentary behavior (SB) has been linked to risk factors of cardiometabolic disease, with inconsistent findings reported in the literature. We aimed to assess the associations of SB with multiple biomarkers of inflammation and insulin resistance in adults. Domain-specific SB, sitting time and moderate-to-vigorous physical activity (MVPA) were measured in 78 adults (mean ± SD 52.0 ± 10.8 y). Body fat percentage (BF%) was assessed using multi-frequency bioelectrical impedance. A blood draw assessed glucose, insulin, C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), leptin, and adiponectin. Adiponectin-leptin ratio (ALR), homeostasis model assessment of insulin resistance (HOMA-IR) and beta-cell function (HOMA-ß) were calculated. Multivariable linear regression analyses, controlling for age, sex, MVPA, and BF%, were used to assess associations. After adjustment for age, sex and MVPA, total SB (7.5 ± 2.5 h/day) was positively associated with leptin, insulin, HOMA-IR, HOMA-ß (Standardized Beta (ß) range 0.21-0.32) and negatively associated with ALR (ß = -0.24, p < 0.05 for all). Similarly, total sitting time (7.2 ± 2.9 h/day) was associated with TNF-α (ß = 0.22) and ALR (ß = -0.26). These associations were attenuated to non-significance after adjustment for BF%. Leisure screen time was detrimentally associated with IL-6 (ß = 0.24), leptin (ß = 0.21), insulin (ß = 0.37), HOMA-IR (ß = 0.37), and HOMA-ß (ß = 0.34), independent of age, sex and MVPA (p < 0.05 for all). Only the associations with insulin (ß = 0.26), HOMA-IR (ß = 0.26), and HOMA-ß (ß = 0.23) remained significant after further controlling BF% (p < 0.05). Self-reported SB is associated with biomarkers of inflammation and insulin resistance, independent of MVPA, and in some cases BF%.

Relationship Between Metabolic Syndrome and Polycystic Ovary Syndrome with Special Reference to C-Reactive Protein.

OBJECTIVES: To estimate C-reactive protein (CRP) levels in Saudi women with and without polycystic ovary syndrome (PCOS), and to investigate the associations between CRP and metabolic syndrome (MetS) components. METHODS: We randomly recruited 200 women with and without PCOS, between 18 and 38 years, in this age-matched case-control study. Study subjects were allocated to 1 of 4 groups according to the presence or absence of MetS. Interviews were conducted with all participants, and anthropometric measurements and blood samples were obtained for subsequent analysis of biochemical variables. RESULTS: Two-thirds of the study population and all study subjects had central obesity. Fasting insulin and homeostasis model assessment insulin resistance index were significantly higher in PCOS and MetS groups than all other groups (P < 0.05). CRP levels were significantly higher among women with PCOS than their age-matched controls, regardless of the presence of MetS (P < 0.05). Body mass index was the only independent predictor of serum high-sensitivity-CRP, accounting for 17% of the variability in circulating levels (ß = 0.407; 95% CI 0.248-0.472, P < 0.0001). CONCLUSIONS: Obesity and insulin resistance are important risk factors for MetS in PCOS. The presence of MetS in PCOS subjects aggravates the proinflammatory state reflected by CRP levels.

Effect of dietary myo-inositol supplementation on the insulin resistance and the prevention of gestational diabetes mellitus: an open-label, randomized controlled trial.

PURPOSE: Myo-inositol (MI) is an insulin-sensitizing dietary supplement, enhancing the transfer of glucose into the cell. Gestational diabetes mellitus (GDM) is characterized by abnormal glucose tolerance, which is associated with elevated insulin resistance. The present study aimed to assess the effect of MI supplementation during pregnancy on the incidence of GDM. METHODS: We performed a single-center, open-label, randomized controlled trial. A cohort of 200 pregnant women at 11-13+6 weeks of gestation were randomly assigned in two groups: MI group (n = 100) and control group (n = 100). The MI group received MI and folic acid (4000 mg MI and 400 mcg folic acid daily), while the control group received folic acid alone (400 mcg folic acid daily) until 26-28 weeks of gestation, when the 75 g Oral Glucose Tolerance Test (OGTT) was performed for the diagnosis of GDM. Clinical and metabolic outcomes were assessed. RESULTS: The incidence of GDM was significantly higher in the MI group (14.9%) compared to the control group (28.5%) (P = 0.024). Women treated with MI had significantly lower OGTT glucose values, than those not treated with MI (P < 0.001). The insulin resistance as assessed by HOMA-IR was significantly lower in the MI group versus control (P = 0.045). Furthermore, MI group had significantly higher insulin sensitivity as measured by the Matsuda Index, compared to the control group (P = 0.037). CONCLUSION: MI supplementation seems to be an effective option to improve the glycemic control of pregnant women and prevent the onset of GDM. TRIAL REGISTRATION: ISRCTN registry: ISRCTN16142533. Registered 09 March 2017.

Postmenopausal women treated for breast cancer with insulin resistance: clinical, analytical, cross-sectional.

This study aims to investigate the potential association between serum levels of cytokines, HSP60, HSP70 and IR (HOMA-IR) in postmenopausal women. We conducted a cross-sectional study involving 381 postmenopausal women, including 94 with a breast cancer diagnosis and 278 without. We analyzed anthropometric and laboratory measurements. Immunoassays were used to measure cytokines (TNF-α, IL-10, and IL-6) as well as heat shock proteins (HSP) 60 and 70 in the serum using the ELISA technique. Women diagnosed with breast cancer showed higher levels of HOMA-IR, IL-6, TNF, and HSP60, and lower levels of IL-10 and HSP70 compared to women without cancer. An association was found between HSP70 and HOMA-IR only in women with breast cancer (ß = 0.22, p = .030; without cancer: ß = 0.04, p = .404), regardless of age, waist circumference, smoking, and physical activity. No associations were observed between cytokines, HSP60, and HOMA-IR in both groups of women. HSP70 is positively associated with IR in women diagnosed with breast cancer.

The Role of Piromelatine on Peripheral and Hippocampal Insulin Resistance in Rat Offspring Exposed to Chronic Maternal Stress.

Prenatal stress (PNS), which alters the hypothalamic-pituitary-adrenal axis function in the offspring, predisposes to insulin resistance (IR) in later life and is associated with numerous disorders, including cognitive and memory impairments. At present, our main goal is to assess the effects of chronic piromelatine (Pir) administration, a melatonin analogue, on PNS-provoked IR in the periphery and the hippocampus in male and female offspring. Pregnant Sprague-Dawley rats were exposed to chronic stress (one short-term stressor on a daily basis and one long-term stressor on a nightly basis) from the first gestation week until birth. Vehicle or Pir 20 mg/kg were administered intraperitoneally for 21 days. Plasma glucose, serum insulin levels, and the homeostasis model assessment of insulin resistance (HOMA-IR) were determined as markers of peripheral IR. For the hippocampal IR assessment, insulin receptors (IRs) and glucose transporter 4 (GLUT4) were examined. Prenatally stressed offspring of both sexes indicated enhanced plasma glucose and serum insulin concentrations, increased HOMA-IR, and decreased hippocampal GLUT4 only in male rats. The PNS-induced changes were corrected by chronic treatment with Pir. The present results suggest that the melatoninergic compound Pir exerts beneficial effects on altered glucose/insulin homeostasis in PNS-exposed offspring.

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.

Hyperleptinemia as a Marker of Various Phenotypes of Obesity and Overweight in Women with Rheumatoid Arthritis and Systemic Lupus Erythematosus.

The objective of the study was to identify different phenotypes of overweight in women with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) based on body mass index (BMI) and serum leptin levels, as well as to determine the frequencies of various metabolic disorders, hypertension, and cardiovascular complications (CVCs) in individual phenotypes. The study included 50 women with RA and 46 with SLE aged 18 to 65 years without a history of diabetes and fasting hyperglycemia. In all patients, the concentration of leptin was determined by ELISA, the concentration of insulin was determined by electrochemiluminescence analysis, and the HOMA-IR index was calculated. Hyperleptinemia was diagnosed at leptin concentrations > 11.1 ng/mL; insulin resistance (IR), at HOMA-IR values ≥ 2.77. Three main phenotypes of overweight were distinguished: "classic" (BMI ≥ 25 kg/m2 + hyperleptinemia), "healthy" (BMI ≥ 25 kg/m2, without hyperleptinemia), "hidden" or "latent" (BMI < 25 kg/m2 + hyperleptinemia), as well as "normal weight" (BMI < 25 kg/m2, without hyperleptinemia). Patients with RA and SLE were similar in age (p = 0.4), disease duration (p = 0.2) and BMI (p = 0.5). Hyperleptinemia was found in 46% of women with RA and in 74% of women with SLE (p = 0.005), and IR was found in 10 and 22% of patients, respectively (p = 0.2). The "classic" phenotype of overweight was diagnosed in 30%, "healthy" in 8%, and "hidden" in 16% of cases with RA and in 44%, 0%, and 30% of cases with SLE, respectively. IR was found in 3% and hypertension in 6% of patients with "normal weight." With the "classic" phenotype, IR (29%) and hypertension (66%) were more common than with "normal weight" (p < 0.01 in all cases); with the "hidden" phenotype, significant differences were obtained only in hypertension frequency (45%; p = 0.0012), but not IR (18%). Three out of four women with a history of cardiovascular complications suffered from "classic" overweight, and one patient had a "normal weight." In women with SLE up to 65 years of age, the frequency of hyperleptinemia, but not IR, is higher than in patients with RA. In both diseases, the "classic" overweight phenotype is most common. In RA, a "hidden" phenotype was detected less often than in SLE, at the same time, a "healthy" phenotype is not characteristic of SLE. The frequency of metabolic disorders and hypertension is low with the "normal weight" and "healthy" phenotype, high with the "classic" phenotype, and intermediate with the "hidden" phenotype.

Association of Serum Adipsin Level with Insulin Resistance and Inflammatory Markers in Newly Diagnosed Type two Diabetes Mellitus Patients.

Adipsin is an anti-inflammatory adipokines and its altered level was seen in obesity and type II DM. Our study investigated the clinical significance of serum adipsin levels as a risk marker for type 2 diabetes and its relationships with insulin resistance and various adipo-cytokines. The study included 110 treatment-naïve T2DM cases and 100 controls of similar age and gender from northern India. Clinical, biochemical, and anthropometric characteristics were all profiled. Serum adipo-cytokines were measured using ELISA methods. Adipsin was significantly inversely correlated with body mass index (BMI), waist circumference, fasting plasma glucose, glycated haemoglobin (HbA1C), total cholesterol (TC), triglyceride (TG), homeostasis model assessment-estimated insulin resistance (HOMA-IR), tumour necrosis factor- α (TNF-α) and interleulin-6 (IL-6) and positively correlated with high-density lipoprotein cholesterol (HDL-C) and homeostasis model assessment of ß-cell function (HOMA-B) (P < 0.05). T2DM occurrence decreased with increasing concentration of adipsin with an odds ratio (OR) of 0.68 (95% CI = 0.58-0.79), P < 0.001. The area under curve (95% CI) for adipsin was 0.70 (0.63 to 0.76) with P < 0.001. The best cutoff value for adipsin to predict T2DM was < 5.50 µg/ml with 47.27% sensitivity and 82.00% specificity. FPG and WC were both independent predictors of serum adipsin levels. Our findings showed that high adipsin levels reduced the likelihood of T2DM and emerged as a potential risk marker in the prediction of T2DM.

Review of facial acanthosis nigricans: Easy to diagnose and difficult to treat marker of hyperinsulinemia/metabolic syndrome.

Facial acanthosis nigricans (FAN) is an increasingly discussed anatomical variation of acanthosis nigricans (AN). Its presentation as brown to black pigmentation with ill-defined blurred margins with varying degree of textural changes commonly over forehead, temporal, and malar regions of the face predominantly in dark-skinned individuals with a male predilection can be confused with other common facial melanoses. Its pathogenesis, clinical features, and management are in many ways similar to in the commonly described areas like neck and major flexural areas. Understanding of FAN has gained momentum in the past decade with studies highlighting its association with various metabolic abnormalities particularly insulin resistance and obesity. It is now being considered to be a cutaneous marker of metabolic syndrome. While there is uniformity in its clinical description, there appears to be scope for further in depth biochemical and histopathological studies to link the pigmentation, altered texture and microscopic changes in individuals presenting with FAN and hyperinsulinemia with or without other features of metabolic syndrome. It awaits a consensus on grading its severity and correlating it with histological features as patients often hesitate to be subjected to a biopsy of the face. This is a review of current literature pertaining to FAN. Newer clinical, dermoscopic, histopathological, and biochemical insights will help to understand this relatively new entity.