Impaired fasting glucose and body mass index as determinants of mortality in ALLHAT: is the obesity paradox real?
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SUBMITTER: Shah RV
PROVIDER: S-EPMC4091725 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectiveTo determine insulin resistance and response in patients with polycystic ovary syndrome (PCOS) and normal glucose tolerance (NGT), impaired fasting glucose (IFG), impaired glucose tolerance, and combined glucose intolerance (CGI).Research design and methodsIn this cross-sectional study, 143 patients with PCOS (diagnosed on the basis of National Institutes of Health criteria) underwent oral glucose tolerance testing (OGTT), and 68 patients also had frequently sampled intravenous glucose tolerance tests. Changes in plasma glucose, insulin, cardiovascular risk factors, and androgens were measured.ResultsCompared with patients with NGT, those with both IFG and CGI were significantly insulin resistant (homeostasis model assessment 3.3 +/- 0.2 vs. 6.1 +/- 0.9 and 6.4 +/- 0.5, P < 0.0001) and hyperinsulinemic (insulin area under the curve for 120 min 973 +/- 69 vs. 1,470 +/- 197 and 1,461 +/- 172 pmol/l, P < 0.0001). Insulin response was delayed in patients with CGI but not in those with IFG (2-h OGTT, insulin 1,001 +/- 40 vs. 583 +/- 45 pmol/l, P < 0.0001). Compared with the NGT group, the CGI group had a lower disposition index (1,615 +/- 236 vs. 987 +/- 296, P < 0.0234) and adiponectin level (11.1 +/- 1.1 vs. 6.2 +/- 0.8 ng/ml, P < 0.0096). Compared with the insulin-resistant tertile of the NGT group, those with IFG had a reduced insulinogenic index (421 +/- 130 vs. 268 +/- 68, P < 0.05). Compared with the insulin-sensitive tertile of the NGT group, the resistant tertile had higher triglyceride and high-sensitivity C-reactive protein (hs-CRP) and lower HDL cholesterol and sex hormone-binding globulin (SHBG). In the entire population, insulin resistance correlated directly with triglyceride, hs-CRP, and the free androgen index and inversely with SHBG.ConclusionsPatients with PCOS develop IFG and CGI despite having significant hyperinsulinemia. Patients with IFG and CGI exhibit similar insulin resistance but very different insulin response patterns. Increases in cardiac risk factors and free androgen level precede overt glucose intolerance.
| S-EPMC2845047 | biostudies-literature
Project description:Background Early (grade 1) cardiac left ventricular diastolic dysfunction (G1DD) increases the risk for heart failure with preserved ejection fraction and may improve with aggressive risk factor modification. Type 2 diabetes, obesity, hypertension, and coronary heart disease are associated with increased incidence of diastolic dysfunction. The genetic drivers of G1DD are not defined. Methods and Results We curated genotyped European ancestry G1DD cases (n=668) and controls with normal diastolic function (n=1772) from Vanderbilt's biobank. G1DD status was explored through (1) an additive model genome-wide association study, (2) shared polygenic risk through logistic regression, and (3) instrumental variable analysis using 2-sample Mendelian randomization (the inverse-variance weighted method, Mendelian randomization-Egger, and median) to determine potential modifiable risk factors. There were no common single nucleotide polymorphisms significantly associated with G1DD status. A polygenic risk score for BMI was significantly associated with increased G1DD risk (odds ratio [OR], 1.20 for 1-SD increase in BMI [95% CI, 1.08-1.32]; P=0.0003). The association was confirmed by the inverse-variance weighted method (OR, 1.89 [95% CI, 1.37-2.61]). Among the candidate mediators for BMI, only fasting glucose was significantly associated with G1DD status by the inverse-variance weighted method (OR, 4.14 for 1-SD increase in fasting glucose [95% CI, 1.55-11.02]; P=0.005). Multivariable Mendelian randomization showed a modest attenuation of the BMI association (OR, 1.84 [95% CI, 1.35-2.52]) when adjusting for fasting glucose. Conclusions These data suggest that a genetic predisposition to elevated BMI increases the risk for G1DD. Part of this effect may be mediated through altered glucose homeostasis.
| S-EPMC9238715 | biostudies-literature
Project description:ObjectiveEvidence regarding the relationship between body mass index (BMI) and reversion to normoglycemia from prediabetes is still limited. The purpose of our study is to survey the link of BMI on reversion to normoglycemia among patients with impaired fasting glucose (IFG).MethodsThis study, a retrospective cohort, covered 32 regions and 11 cities in China and collected 258,74 IFG patients who underwent a health check from 2010 to 2016. We investigated the association between baseline BMI and reversion to normoglycemia in patients with IFG using the Cox proportional-hazards regression model. The nonlinear relationship between BMI and reversion to normoglycemia was determined using a Cox proportional hazards regression with cubic spline functions and smooth curve fitting. In addition, we also performed a series of sensitivity analyses and subgroup analyses. A competing risk multivariate Cox regression was performed using progression to diabetes as a competing risk for reversal of normoglycemic events.ResultsAfter adjusting covariates, the results showed that BMI was negatively related to the probability of reversion to normoglycemia (HR=0.977, 95%CI:0.971-0.984). Compared with participants with normal BMI(<24kg/m2), overweight (BMI:24-28kg/m2) participants with IFG had a 9.9% lower probability of returning to normoglycemia (HR=0.901,95%CI:0.863-0.939), while obese patients (BMI ≥ 28kg/m2) had a 16.9% decreased probability of reverting from IFG to normoglycemia (HR=0.831,95%CI:0.780-0.886). There was also a nonlinear relationship between them, and the inflection point of BMI was 21.7kg/m2. The effect sizes (HR) on the left sides of the inflection point were 0.972(95%CI:0.964-0.980). The competing risks multivariate Cox's regression and sensitivity analysis demonstrated the robustness of our results.ConclusionThis study demonstrates a negative and nonlinear relationship between BMI and reversion to normoglycemia in Chinese patients with IFG. Minimizing BMI to 21.7 kg/m2 in patients with IFG through aggressive intervention may significantly increase the probability of returning to normoglycemia.
| S-EPMC10151769 | biostudies-literature
Project description:IntroductionWe investigated the associations of pre-surgical body mass index (BMI) with bladder cancer outcomes in patients treated with radical cystectomy.MethodsWe retrospectively analyzed data from 488 bladder cancer patients treated with radical cystectomy between 1994 and 2007 and followed up until 2016. Cox regression with step function (time-segment analysis) was conducted for overall survival because the proportional hazard assumption was violated.ResultsOf 488 bladder cancer patients, 155 (31.8%) were normal weight, 186 (38.1%) were overweight, and 147 (30.1%) were obese. During the median followup of 59.5 months, 363 (74.4%) patients died, including 197 (40.4%) from bladder cancer. In adjusted Cox regression analyses, BMI was not significantly associated with bladder cancer-specific survival for overweight (hazard ratio [HR] 0.79, 95% confidence interval [CI] 0.57-1.10, p=0.16) or obese (HR 0.76, 95% CI 0.52-1.09, p=0.13) patients. In the Cox regression with step function for overall survival, the time interaction was significant overall (p=0.020) and specifically for over-weight patients (p=0.006). In the time-segment model, the HR for overweight during the first 63 months was 0.66 (95% CI 0.49-0.90, p=0.008), whereas it was 1.41 (95% CI 0.89-2.23, p=0.14) after 63 months. Although not statistically significant, a similar pattern was observed for obese patients.ConclusionsOur findings suggest that overweight and obese bladder cancer patients had better outcomes within the first five years after radical cystectomy; however, there were no differences in longer-term survival. These data suggest that the obesity paradox in bladder cancer patients treated with radical cystectomy may be short-lived.
| S-EPMC9119589 | biostudies-literature
Project description:BackgroundAnimal studies suggest sphingolipids as an early marker of impaired glucose metabolism; however, research in humans is limited. We evaluated whether individual sphingolipid species were associated with fasting plasma glucose and incident impaired fasting glucose in a longitudinal cohort study.MethodsWe measured 15 sphingolipid species from blood samples collected in 2001-2003 from 2145 participants without prevalent diabetes in the Strong Heart Family Study. Fasting plasma glucose was measured in blood samples collected at baseline and follow-up (mean 5.5?years after baseline).FindingsThe average age of study participants was 38?years; 41% were men. Ceramide, sphingomyelin, and glucosylceramide species levels were higher in older participants; lactosyl-ceramide levels were higher in participants with lower BMIs. In adjusted analyses, greater concentrations of most ceramide species and lower lactosyl-ceramide with palmitic acid (LC-16) were associated with higher glucose levels at baseline. We did not observe associations of sphingomyelin species or glucosyl-ceramide species with glucose levels. Associations of sphingolipid levels with fasting glucose levels at follow-up were similar but had greater uncertainty than associations with baseline glucose. Although no statistically significant associations of sphingolipids with incident impaired fasting glucose were present, results were similar to glucose analyses.InterpretationWe identified several ceramide species associated with higher fasting glucose levels and one sphingolipid, LC-16, that was associated with lower fasting glucose levels. These findings compliment previous research, which linked these sphingolipids with fasting insulin levels, and suggest that higher levels of these ceramides and lower LC-16 may be an early marker of impaired glucose metabolism. FUND: US National Institutes Health.
| S-EPMC6444022 | biostudies-literature
Project description:BackgroundTo investigate the factors associated with elevated fibrinogen (Fbg) levels in COVID-19 patients with and without diabetes (DM) and impaired fasting glucose (IFG).MethodsAccording to whether or not their glucose metabolism was impaired, COVID-19 patients were subdivided into 2 groups: 1) with DM and IFG, 2) control group. Their demographic data, medical history, signs and symptoms, laboratory results, and final clinical results were analyzed retrospectively.Results28 patients (16.3%) died during hospitalization, including 21 (29.2%) in group 1 and 7 (7.0%) in group 2 (P < 0.001). Fbg levels in groups 1 and 2 were higher than the normal range, at 5.6 g/L (IQR 4.5-7.2 g/L) and 5.0 g/L (IQR 4.0-6.1 g/L), respectively (P = 0.009). Serum ferritin levels, C-reactive protein (CRP), interleukin-6 (IL-6), IL-8, tumor necrosis factor-α (TNF-α), triglycerides (TG) were significantly increased in group 1 compared to those in the control. TG levels were 1.3 mmol/L in the control, while that in group 1 was 1.8 mmol/L. Multiple linear regression showed that the predicting factors of Fbg in the control group were serum ferritin and CRP, R2 = 0.295; in group 1, serum ferritin, CRP, and TG, R2 = 0.473.ConclusionsFbg in all COVID-19 patients is related to serum ferritin and CRP involved in inflammation. Furthermore, in COVID-19 patients with insulin resistance, Fbg is linearly positively correlated with TG. This suggests that regulation of TG, insulin resistance, and inflammation may reduce hypercoagulability in COVID-19 patients, especially those with insulin resistance.
| S-EPMC7995294 | biostudies-literature
Project description:AimThe present study evaluated the relative influence of body mass index (BMI) on insulin resistance (IR), first-phase insulin secretion (FPIS), second-phase insulin secretion (SPIS), and glucose effectiveness (GE) at a fixed fasting plasma glucose level in an older ethnic Chinese population.MethodsIn total, 265 individuals aged 60 years with a fasting plasma glucose level of 5.56 mmol/L were enrolled. Participants had BMIs of 20.0-34.2 kg/m2. IR, FPIS, SPIS, and GE were estimated using our previously developed equations. Pearson correlation analysis was conducted to assess the correlations between the four diabetogenesis factors and BMI. A general linear model was used to determine the differences in the percentage of change among the four factor slopes against BMI.ResultsSignificant correlations were observed between BMI and FPIS, SPIS, IR, and GE in both women and men, which were higher than those reported previously. In men, BMI had the most profound effect on SPIS, followed by IR, FPIS, and GE, whereas in women, the order was slightly different: IR, followed by FPIS, SPIS, and GE. Significant differences were observed among all these slopes, except for the slopes between FPIS and SPIS in women (p = 0.856) and IR and FPIS in men (p = 0.258).ConclusionsThe contribution of obesity to all diabetes factors, except GE, was higher than that reported previously. BMI had the most profound effect on insulin secretion in men and on IR in women in this 60-year-old cohort, suggesting that lifestyle modifications for obesity reduction in women remain the most important method for improving glucose metabolism and preventing future type 2 diabetes mellitus.
| S-EPMC5788342 | biostudies-literature
Project description:BACKGROUND:Around 308 million people worldwide are estimated to have impaired glucose tolerance (IGT); 25% to 75% of these will develop diabetes within a decade of initial diagnosis. At diagnosis, half will have tissue-related damage and all have an increased risk for coronary heart disease. OBJECTIVES:The objective of this review was to assess the effects and safety of Chinese herbal medicines for the treatment of people with impaired glucose tolerance or impaired fasting glucose (IFG). SEARCH STRATEGY:We searched the following databases: The Cochrane Library, PubMed, EMBASE, AMED, a range of Chinese language databases, SIGLE and databases of ongoing trials. SELECTION CRITERIA:Randomised clinical trials comparing Chinese herbal medicines with placebo, no treatment, pharmacological or non-pharmacological interventions in people with IGT or IFG were considered. DATA COLLECTION AND ANALYSIS:Two authors independently extracted data. Trials were assessed for risk of bias against key criteria: random sequence generation, allocation concealment, blinding of participants, outcome assessors and intervention providers, incomplete outcome data, selective outcome reporting and other sources of bias. MAIN RESULTS:This review examined 16 trials lasting four weeks to two years involving 1391 participants receiving 15 different Chinese herbal medicines in eight different comparisons. No trial reported on mortality, morbidity or costs. No serious adverse events like severe hypoglycaemia were observed. Meta-analysis of eight trials showed that those receiving Chinese herbal medicines combined with lifestyle modification were more than twice as likely to have their fasting plasma glucose levels return to normal levels (i.e. fasting plasma glucose <7.8 mmol/L and 2hr blood glucose <11.1 mmol/L) compared to lifestyle modification alone (RR 2.07; 95% confidence intervall (CI) 1.52 to 2.82). Those receiving Chinese herbs were less likely to progress to diabetes over the duration of the trial (RR 0.33; 95% CI 0.19 to 0.58). However, all trials had a considerable risk of bias and none of the specific herbal medicines comparison data was available from more than one study. Moreover, results could have been confounded by rates of natural reversion to normal glucose levels. AUTHORS' CONCLUSIONS:The positive evidence in favour of Chinese herbal medicines for the treatment of IGT or IFG is constrained by the following factors: lack of trials that tested the same herbal medicine, lack of details on co-interventions, unclear methods of randomisation, poor reporting and other risks of bias.
| S-EPMC3191296 | biostudies-literature
Project description:BackgroundTo investigate the effect of body mass index (BMI) on clinical outcomes after robotic cardiac surgery, and to explore the postoperative obesity paradox.MethodsThe data of 146 patients who underwent robotic cardiac surgery under cardiopulmonary bypass (CPB) from July 2016 to June 2022 in Daping Hospital of Army Medical University were retrospectively analyzed, and their demographic data and related clinical data were statistically analyzed. The mean age was (42.88 ± 13.01) years, 55 (37.67%) were male and 91 (62.33%) were female. Patients were divided into 3 groups according to preoperative BMI: lean group (BMI < 18.5 kg/m2; n = 17; 11.64%), normal group (BMI 18.5 kg/m2 to 23.9 kg/m2; n = 81; 55.48%), and overweight and obese group (BMI ≥ 24 kg/m2; n = 48; 32.88%). Multivariate analysis was performed to compare clinical outcomes across BMI groups.ResultsPreoperative data in different BMI groups showed that there were statistically significant differences in age, height, weight, body surface area (BSA), diabetes, left atrial anteroposterior diameter (LAD), triglyceride (TG), and high-density lipoprotein (HDL) (all P < 0.05). Postoperative clinical outcomes showed that there was no statistical difference between the lean group and the normal group; the intensive care unit stay and postoperative hospital stay in the overweight and obese group were significantly higher than those in the normal group (P < 0.05), and the risk of postoperative cardiac surgery-related acute kidney injury (CSA-AKI) was significantly increased (P = 0.021); further Multiple Binary Logistic Regression Analysis suggested that preoperative TG (OR = 1.772, 95% CI 1.068-2.942, P = 0.027) and operation time ≥ 300 min (OR = 3.823, 95% CI 1.098-13.308, P = 0.035) were independent risk factors for postoperative CSA-AKI.ConclusionsOverweight and obese patients had significantly prolonged intensive care unit stay and postoperative hospital stay after robotic cardiac surgery, and significantly increased incidence of postoperative CSA-AKI, which did not support the obesity paradox; preoperative TG and operation time ≥ 300 min were independent risk factors for postoperative CSA-AKI.
| S-EPMC10207724 | biostudies-literature
Project description:Obesity and type 2 diabetes are major public health issues with known interdependence. Genetic variants have been associated with obesity, type 2 diabetes, or both; thus, we hypothesize that some single nucleotide polymorphisms (SNPs) associated with both conditions may be mediated through obesity to affect type 2 diabetes or vice versa. We propose a framework for bidirectional mediation analyses. Simulations show that this approach accurately estimates the parameters, whether the mediation is unidirectional or bidirectional. In many scenarios, when the mediator is regressed on the initial variable and the outcome is regressed on the mediator and the initial variable, the resulting residuals are correlated because of other unmeasured covariates not in the model. We show that the proposed model provides accurate estimates in this scenario, too. We applied the proposed approach to investigate the mediating effects of SNPs associated with type 2 diabetes and obesity using genetic data from the Multi-Ethnic Study of Atherosclerosis cohort. Specifically, we used body mass index (BMI) as a measure for obesity and fasting glucose as a measure for type 2 diabetes. We evaluated the top 6 SNPs associated with both BMI and fasting glucose. Two SNPs (rs3752355 and rs6087982) had indirect effects on BMI mediated through fasting glucose [0.2677; 95% confidence interval (CI) (0.0007, 0.6548) and 0.3301; 95% CI (0.0881, 0.8544), respectively]. The remaining four SNPs (rs7969190, rs4869710, rs10201400, and rs12421620) directly affect BMI and fasting glucose without mediating effects.
| S-EPMC6188813 | biostudies-literature