Insulin Resistance In Healthy Individuals Research Articles

The association between triglyceride-glucose atherogenic predictor index and central retinal artery occlusion

Purpose: Central retinal artery occlusion (CRAO) is an acute ischemic event causing severe visual loss and is a precursor to further cerebrovascular and cardiovascular events. The triglyceride-glucose index (TyG) indicates insulin resistance in healthy individuals. Numerous research links the TyG index to metabolic syndrome, hypertension, and new-onset diabetes. Recent research also suggests its role as a sign of atherosclerosis in cardiovascular diseases, with potential clinical significance in assessing vascular damage. In this study, the relationship between CRAO and TyG index was evaluated. Materials and Methods: This case-control study involved 116 adults (50 CRAO patients and 66 control subjects without chronic eye diseases) at our hospital from January 2018 to March 2023. The TyG index was formulated as ln[fasting TG (mg/dL) × fasting plasma glucose (mg/dL)/2]. Results: The CRAO group had a mean age of 65.0±14.7 years, with 27 (55.1 % 54) females. The control group had a mean age of 61.2±12.1 years, with 32 (48.5) females. The mean TyG index was 9.05±0.7 in the CRAO group and 8.7±0.7 in controls, a statistically significant difference. Univariate regression analysis showed an association between the TyG index and CRAO (OR=2.04; CI: 1.11-3.73). This association remained significant in multivariate logistic regression analysis (OR=1.88; CI: 1.01-3.50). Conclusion: This study found a significantly higher mean TyG index, an atherogenic indicator, in CRAO patients compared to controls.

An acute exercise at low to moderate intensity attenuated postprandial lipemia and insulin responses

ObjectiveThe purpose of this study was to investigate the effects of different exercise intensities on postprandial lipemia (PHTG) and insulin resistance in healthy individuals. MethodsParticipants were 10 adult males with normal fasting triglyceride (TG) concentrations (age = 34 ± 2.8 y, body mass = 72.9 ± 2.4 kg, fasting plasma TG = 1.36 ± 0.18 mmol/l, VO2max = 43.7 ± 3.0 ml/kg/min, fasting glucose = 5.2 ± 0.2 mmol/l and fasting Homeostatic Model Assessment for Insulin Resistance (HOMA2-IR) = 1.7 ± 0.3). In this study, each participant performed a control trial (Ctr, no exercise), and 3 exercise trials at 40 % (40%T), 60 % (60%T), and 70 % (70%T) of their VO2max. In the exercise trials, participant jogged on a treadmill for 1 h at a designated intensity. A fat-rich meal was consumed by each participant 12 h after exercise. Blood samples were taken at 0 h (before the meal), and 2 h, 4 h, 6 h, 8 h, and 24 h after the meal. The plasma TG, area score under TG concentration curve over an 8 h-period (TG tAUC) after the meal, and HOMA2-IR were analyzed. ResultsOur results showed that at 2 h, 4 h, and 6 h after the meal, TG in all exercise trials were lower than Ctr (p < 0.05) but did not differ from each other. All the exercise trials were lower in TG tAUC scores than Ctr (p < 0.02), but differences were not observed among the exercise trials. In comparison to Ctr, a significant difference in HOMA2-IR in both 60 % T and 70 % T (p < 0.05 and p < 0.01, respectively) was observed, but not in 40 % T. ConclusionThe results suggest that exercising at low to moderate exercise intensity for 1 h sufficiently attenuates a fat meal induced PHTG. Moderate exercise intensity also effectively mitigates insulin resistance.

Evaluation of the Relationship Between Smoking and Insulin Resistance: A Case-Control Study.

In recent years, there has been a surge in research focusing on the link between smoking and insulin resistance in the context of obesity and diabetes. In this study, our objective was to investigate the relationship between smoking and insulin resistance. This is a case-control study. The case and control groups were formed using the hospital patient information database and clinically randomized using data obtained, including age, gender, height, and weight. The case group for this study consisted of smokers, whereas the control group consisted of non-smokers. Chi-square tests were used to compare numbers and rates, and independent sample t-tests were used for the averages. Binary logistic regression analysis was performed between the case and control groups. According to logistic regression analysis, the odds ratio for non-smokers was 0.59 (0.31-1.14). The risk of insulin resistance is decreased by 41% non-significantly in non-smokers. The odds ratio for age was 1.03 (1.01-1.05). When the age variable increases by one unit, the risk of insulin resistance increase by 1.03 times. Our study found no significant relationship between smoking and insulin resistance in healthy individuals.The relationship between smoking and insulin resistance, as reported in the scientific literature, may be suggestive of an association in which smoking exacerbates insulin resistance as a result of other contributing factors rather than serving as a direct causal factor. Further studies are warranted to elucidate the potential mechanisms underlying this association fully.

Relationship Between Insulin Sensitivity and β-Cell Secretion in Nondiabetic Subjects with Rheumatoid Arthritis.

In nondiabetic healthy individuals, insulin secretion and sensitivity are linked by a negative feedback loop characterized by a hyperbolic function. We aimed to study the association of traditional insulin resistance (IR) factors with insulin secretion and sensitivity, and to determine whether the hyperbolic equilibrium of this relation is preserved in patients with rheumatoid arthritis (RA). This was a cross-sectional study encompassing 361 nondiabetic individuals: 151 with RA and 210 controls. Insulin, C-peptide, and IR indices by homeostatic model (HOMA2) were assessed. A multivariable analysis was performed to evaluate the differences in the correlation of traditional IR-related factors with glucose homeostasis molecules, as well as IR indices between patients and controls. Nonlinear regression analysis was used to assess the hyperbolic relation of insulin sensitivity and secretion. HOMA2-IR indices were higher in patients with RA than controls. Hepatic insulin extraction, as assessed by the insulin:C-peptide molar ratio, was lower in patients with RA after multivariable analysis (0.08 ± 0.02 vs 0.14 ± 0.07, p < 0.001). Traditional IR-related factors showed significantly lower adjusted correlation coefficients with IR indices in patients with RA. The association between insulin sensitivity and secretion showed a different hyperbolic relation in patients with RA: the variability explained by the curve was lower in RA (nonlinear r2 = 0.845 vs r2 = 0.928, p = 0.001) and β coefficients (-0.74, 95% CI -0.77 to -0.70 vs -1.09, 95% CI -1.17 to -1.02, ng/ml, p < 0.001) were different in RA. The traditional factors associated with IR in healthy individuals are less related to IR in patients with RA. Insulin sensitivity and secretion yield a different hyperbolic equilibrium in RA.

Beta-cell function is associated with carotid intima-media thickness independently of insulin resistance in healthy individuals

Beta-cell function is associated with carotid intima-media thickness independently of insulin resistance in healthy individuals

Beta-cell function is associated with carotid intima-media thickness independently of insulin resistance in healthy individuals

Beta-cell function is associated with carotid intima-media thickness independently of insulin resistance in healthy individuals

Relationship Between Glucocorticoids and Insulin Resistance in Healthy Individuals.

BackgroundThe aim of this study was to determine the correlation between glucocorticoids (GCs) and insulin resistance (IR) in healthy individuals by conducting a systematic meta-analysis.Material/MethodsA systematic literature review was conducted using 9 electronic databases. Only case-control studies investigating fasting plasma glucose (FPG) and IR were enrolled based on strictly established selection criteria. Statistical analyses were performed by Stata software, version 12.0 (Stata Corporation, College Station, Texas, USA).ResultsAmong 496 initially retrieved articles, only 6 papers published in English were eventually included in this meta-analysis. A total of 201 healthy individuals (105 in GC group and 96 in control group) were included in the 6 studies. In 4 of these 6 studies, dexamethasone was used, and in the other 2 studies prednisolone was given. This meta-analysis revealed that the FPG, fasting insulin (FINS), and homeostasis model assessment of insulin resistance (HOMA-IR) levels in the GC group were all significantly higher than that in the control group (FPG: SMD=2.65, 95%CI=1.42~3.88, P<0.001; FINS: SMD=2.48, 95%CI=1.01~3.95, P=0.001; HOMA-IR: SMD=38.30, 95%CI=24.38~52.22, P<0.001).ConclusionsIn conclusion, our present study revealed that therapies using GCs might result in elevated FPG, FINS, and HOMA-IR, and thereby contribute to IR in healthy individuals.

Beta-cell function is associated with carotid intima-media thickness independently of insulin resistance in healthy individuals.

It is a common belief that early atherosclerosis in prediabetes is causally linked to endothelial insulin resistance. Another condition, a low insulin secretion, may be associated with insufficient insulin action on the vascular wall and consequently favor atherosclerosis. Our aim was to test this hypothesis in people without diabetes, taking into account the gold-standard measurement of insulin sensitivity, a major confounder in the relationship between insulin secretion and atherosclerosis. We studied the European Relationship between Insulin Sensitivity and Cardiovascular Risk cohort of 451 men and 593 women (44 ± 8 years, mean ± SD) who were free of diabetes, hypertension, dyslipidemia, and other known chronic or acute conditions. All underwent an oral glucose tolerance test, a euglycemic-hyperinsulinemic clamp (M/I measured insulin sensitivity), and B-mode carotid ultrasound. Intima-media thickness (IMT) in the common carotid artery was negatively associated with insulin secretion indexes, with Spearman partial correlation coefficients: -0.09, -0.08, -0.06 for respectively, the disposition index, the early insulin response and the beta cell glucose sensitivity, after adjusting for established factors, including clamp-measured insulin sensitivity (all P < 0.05). For quartiles 1 (lowest) to 4 of the disposition index, the covariate-adjusted geometric means of IMT (mm) were 0.605 (95% confidence interval: 0.596-0.614), 0.596 (0.587-0.605), 0.597 (0.587-0.606), and 0.586 (0.577-0.596) (Ptrend = 0.004). Similar results were found for the two other surrogate measures of insulin secretion. No interaction with sex was observed. Insulin secretion was associated with early carotid atherosclerosis in nondiabetic individuals, independently of other risk factors, including insulin sensitivity measured by the gold-standard method.

Insulin resistance in breast cancer: relevance and clinical implications

Breast cancer risk is increased in women who have attributes of the insulin resistance syndrome, such as obesity (postmenopausal), central obesity (premenopausal and postmenopausal), high endogenous insulin levels, clinical diabetes and physical inactivity. There is a large body of evidence that obesity is associated with a 25 to 50% relative increase in risk of breast cancer recurrence or death, with adverse effects that appear to be independent of hormone receptor status. Obesity, particularly when it is central, is strongly associated with insulin resistance in healthy individuals and breast cancer patients. Several studies have shown that higher insulin and/or C-peptide levels (a marker of insulin secretion), both of which are linked to insulin resistance, are associated with an increased risk of recurrence and death in women with early stage breast cancer, even in the absence of diabetes. Risk is increased twofold to threefold in those with insulin levels in the highest (versus lowest) quartile. Data from our group suggest that these prognostic associations of insulin are most marked in the first 5 years post diagnosis. A role of insulin in breast cancer outcomes is biologically plausible given overexpression of insulin receptors (IR), most frequently the fetal form of the receptor (IR-A), by the majority of human breast cancers. IR-A often hybridizes with insulin-like growth factor 1 receptors to stimulate mitogenic signaling pathways; hybrid receptor activation has been associated with poor clinical outcomes. The current observational and preclinical evidence linking insulin to breast cancer is sufficiently compelling that neoadjuvant and adjuvant intervention studies have been initiated to evaluate clinical anti-cancer effects of metformin, an agent that lowers insulin levels and has other potential non-insulin-mediated anti-cancer effects (mainly through activation of adenosine monophosphate-activated protein kinase). Early results from window of opportunity neoadjuvant studies suggest short-term, single-agent metformin (2 to 3 weeks) lowers insulin levels, reduces proliferation and increases apoptosis. NCIC MA32, an ongoing randomized, multicenter, placebo-controlled, adjuvant trial involving 3,582 women with early stage breast cancer, will provide more definitive evidence regarding potential anti-cancer effects. Additional studies of metformin in the metastatic setting are underway and/or planned. Because other factors (such as inflammation, adipocytokines (leptin, adiponectin), higher estrogen levels) may also mediate prognostic effects of obesity and/or insulin resistance in breast cancer, additional research targeting these mediators as well as obesity per se is also needed.

Signal Transducer and Activator of Transcription 3 (STAT3) Mediates Amino Acid Inhibition of Insulin Signaling through Serine 727 Phosphorylation

Nutrient overload is associated with the development of obesity, insulin resistance, and type II diabetes. High plasma concentrations of amino acids have been found to correlate with insulin resistance. At the cellular level, excess amino acids impair insulin signaling, the mechanisms of which are not fully understood. Here, we report that STAT3 plays a key role in amino acid dampening of insulin signaling in hepatic cells. Excess amino acids inhibited insulin-stimulated Akt phosphorylation and glycogen synthesis in mouse primary hepatocytes as well as in human hepatocarcinoma HepG2 cells. STAT3 knockdown protected insulin sensitivity from inhibition by amino acids. Amino acids stimulated the phosphorylation of STAT3 at Ser(727), but not Tyr(705). Replacement of the endogenous STAT3 with wild-type, but not S727A, recombinant STAT3 restored the ability of amino acids to inhibit insulin signaling, suggesting that Ser(727) phosphorylation was critical for STAT3-mediated amino acid effect. Furthermore, overexpression of STAT3-S727D was sufficient to inhibit insulin signaling in the absence of excess amino acids. Our results also indicated that mammalian target of rapamycin was likely responsible for the phosphorylation of STAT3 at Ser(727) in response to excess amino acids. Finally, we found that STAT3 activity and the expression of its target gene socs3, known to be involved in insulin resistance, were both stimulated by excess amino acids and inhibited by rapamycin. In conclusion, our study reveals STAT3 as a novel mediator of nutrient signals and identifies a Ser(727) phosphorylation-dependent and Tyr(705) phosphorylation-independent STAT3 activation mechanism in the modulation of insulin signaling.

C-Jun NH2-Terminal Kinase Activity in Subcutaneous Adipose Tissue but Not Nuclear Factor-κB Activity in Peripheral Blood Mononuclear Cells Is an Independent Determinant of Insulin Resistance in Healthy Individuals

OBJECTIVEChronic low-grade activation of the immune system (CLAIS) predicts type 2 diabetes via a decrease in insulin sensitivity. Our study investigated potential relationships between nuclear factor-κB (NF-κB) and c-Jun NH2-terminal kinase (JNK) pathways—two pathways proposed as the link between CLAIS and insulin resistance.RESEARCH DESIGN AND METHODSAdiposity (dual-energy X-ray absorptiometry), waist-to-hip ratio (WHR), and insulin sensitivity (M, hyperinsulinemic-euglycemic clamp) were measured in 22 healthy nondiabetic volunteers (aged 29 ± 11 years, body fat 28 ± 11%). NF-κB activity (DNA-binding assay) and JNK1/2 activity (phosphorylated JNK) were assessed in biopsies of the vastus lateralis muscle and subcutaneous adipose tissue and in peripheral blood mononuclear cell (PBMC) lysates.RESULTSNF-κB activities in PBMCs and muscle were positively associated with WHR after adjustment for age, sex, and percent body fat (both P < 0.05). NF-κB activity in PBMCs was inversely associated with M after adjustment for age, sex, percent body fat, and WHR (P = 0.02) and explained 16% of the variance of M. There were no significant relationships between NF-κB activity and M in muscle or adipose tissue (both NS). Adipose-derived JNK1/2 activity was not associated with obesity (all P> 0.1), although it was inversely related to M (r = −0.54, P < 0.05) and explained 29% of its variance. When both NF-κB and JNK1/2 were examined statistically, only JNK1/2 activity in adipose tissue was a significant determinant of insulin resistance (P = 0.02).CONCLUSIONSJNK1/2 activity in adipose tissue but not NF-κB activity in PBMCs is an independent determinant of insulin resistance in healthy individuals.

Obesity, insulin resistance and oxidative stress: implication for breast carcinogenesis.

Abstract Abstract #6025 Background: Obesity is associated with a modest increase in the risk of postmenopausal breast cancer (RR = 1.5 – 2.0); but, because nearly a third of the U.S. population is obese, the population attributable risk is estimated at 15%. Obesity can cause insulin resistance culminating in Type II diabetes. Notably, breast cancer incidence is significantly increased in the years preceding a diagnosis of type II diabetes. Because IGFBP-1 expression is tightly regulated by insulin, it is an excellent marker of insulin resistance in healthy individuals.&amp;#x2028; Methods: These data are based on well-annotated prospectively acquired baseline blood and breast tissue samples from 72 high risk women between the ages of 37 and 86 years who participated in a chemoprevention trial. None of the women had been diagnosed with Type II diabetes. Women with plasma IGFBP1 levels in the lowest tertile (mean 2.1 ng/ml) were classified as insulin-resistant.&amp;#x2028; Results: Plasma IGFBP1 was strongly inversely correlated with BMI (R2 = 0.247, P &amp;lt; 0.0001). Insulin-resistant women had marginally higher mean plasma free estradiol levels than women not classified as insulin-resistant (2.13 x 10-12M versus 1.53 x 10-12M, P = 0.072). There was no difference in plasma IGF1, IGF2, or IGFBP3 levels. Illumina whole genome expression microarray data was available for breast tissue from 55 women. Women classified as insulin-resistant showed evidence of an adaptive response to oxidative stress based on significant upregulation of NQO1, GSTK1, CYP4ZP2, and SRXN1 (P &amp;lt; 0.001).&amp;#x2028; Conclusions: Marginally increased circulating estradiol may contribute to the increased breast cancer risk observed in insulin-resistant women. However, insulin resistance increases oxidative stress in breast tissue and may promote carcinogenesis through induction of oxidative DNA damage. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6025.

Anthropometrical measures are easily obtainable sensitive and specific predictors of insulin resistance in healthy individuals

Global Heart is the official and primary publication of the World Heart Federation, offering a platform for the dissemination of knowledge on research, developments, trends, solutions and public health programmes in the area of cardiovascular disease. Global Heart welcomes research results, points of view and educational material on the prevention, treatment and control of cardiovascular disease with a special focus on low and middle-income countries which are facing the brunt of epidemiological transition.Global Heart strongly encourages authors to adhere to CONSORT, STROBE, STARD, and PRISMA guidelines for reporting of clinical trials, observational studies, diagnostic test accuracy papers, and systematic reviews or meta-analyses. Authors are required for submission to download and complete the appropriate Equator Network checklist: http://www.equator-network.org/.

Short-term administration of flavanol-rich cocoa decreases blood pressure levels and insulin resistance in healthy individuals

Short-term administration of flavanol-rich cocoa decreases blood pressure levels and insulin resistance in healthy individuals

Dexamethasone-induced insulin resistance shows no gender difference in healthy humans

Recent reports suggest that lipid-induced insulin resistance is more pronounced in men than in women. Whether such gender difference exists for other factors known to induce insulin resistance in healthy individuals remains unknown. We therefore assessed whether glucocorticoid-induced insulin resistance differs in men and women. The insulin sensitivity and insulin secretion of 8 women and 7 men, all non obese and healthy, were evaluated with or without administration of dexamethasone (2 mg/day during 2 days) by means of a two-step hyperglycemic clamp. Dexamethasone decreased insulin sensitivity to the same extent in men and women. The relative increases in insulin concentration observed after dexamethasone in the basal state, during the first phase of insulin release and at the two steps of hyperglycemia were similar in men and women. The hyperinsulinemia thus attained allowed to fully compensate for insulin resistance in both genders. The effects of glucocorticoids on insulin sensitivity and insulin secretion show no gender difference in healthy humans.

Relation of the White Blood Cell Count to Obesity and Insulin Resistance: Effect of Race and Gender

Recent reports suggest that the white blood cell (WBC) count is related to plasma insulin concentrations and insulin resistance in healthy individuals. The present study examines whether these relations are independent of obesity and the pattern of body fat distribution and tests whether race and gender affect these relations. WBC counts, insulin responses to a 75 gram oral glucose tolerance test (OGTT) and glucose disposal during a two-step hyperinsulinemic euglycemic clamp were measured in 300 men and women (149 Pima Indians, 100 whites, and 51 blacks) with a wide range of obesity. WBC counts were lower in blacks than Pima Indians or whites and tended to be higher in women than men. The subgroups were comparable in age and body weight, but percent body fat and plasma insulin concentrations were higher and glucose disposal during the glucose clamp was lower in Pima Indians than in blacks or whites. In the group as a whole, the WBC count correlated with obesity (body mass index and percent body fat), the waist to thigh ratio (an index of the pattern of body fat distribution), and plasma insulin concentrations and was negatively related to age and glucose disposal during the clamp. In multiple regression analyses, only age, race and obesity were significantly associated with the WBC count. When the analyses were restricted to Pima men, in whom correlations between the WBC count and the metabolic variables appeared the strongest, the WBC count remained significantly associated with plasma insulin concentrations, but not glucose disposal, after controlling for age and obesity. The results of this study indicate that age, race, and obesity are significantly associated with the WBC count in healthy individuals. Plasma insulin concentrations, but not insulin resistance per se, may also be weakly associated with the WBC count, but this may be population specific.

Eccentric exercise induces transient insulin resistance in healthy individuals.

Euglycemic-hyperinsulinemic clamps were performed on six healthy untrained individuals to determine whether exercise that induces muscle damage also results in insulin resistance. Clamps were performed 48 h after bouts of predominantly 1) eccentric exercise [30 min, downhill running, -17% grade, 60 +/- 2% maximal O2 consumption (VO2max)], 2) concentric exercise (30 min, cycle ergometry, 60 +/- 2% VO2max), or 3) without prior exercise. During the clamps, euglycemia was maintained at 90 mg/dl while insulin was infused at 30 mU.m-2.min-1 for 120 min. Hepatic glucose output (HGO) was determined using [6,6-2H]glucose. Eccentric exercise caused marked muscle soreness and significantly elevated creatine kinase levels (273 +/- 73, 92 +/- 27, 87 +/- 25 IU/l for the eccentric, concentric, and control conditions, respectively) 48 h after exercise. Insulin-mediated glucose disposal rate was significantly impaired (P less than 0.05) during the clamp performed after eccentric exercise (3.47 +/- 0.51 mg.kg-1.min-1) compared with the clamps performed after concentric exercise (5.55 +/- 0.94 mg.kg-1.min-1) or control conditions (5.48 +/- 1.0 mg.kg-1.min-1). HGO was not significantly different among conditions (0.77 +/- 0.26, 0.65 +/- 0.27, and 0.66 +/- 0.64 mg.kg-1.min-1 for the eccentric, concentric, and control clamps, respectively). The insulin resistance observed after eccentric exercise could not be attributed to altered plasma cortisol, glucagon, or catecholamine concentrations. Likewise, no differences were observed in serum free fatty acids, glycerol, lactate, beta-hydroxybutyrate, or alanine. These results show that exercise that results in muscle damage, as reflected in muscle soreness and enzyme leakage, is followed by a period of insulin resistance.