Estimation of fatty liver disease clinical role on glucose metabolic remodelling phenotypes and T2DM onset.

INTRODUCTION: Metabolic syndrome (MetS), prediabetes (PreDM) and Fatty Liver Disease (FLD) share pathophysiological pathways concerning type 2 diabetes mellitus (T2DM) onset. The non-invasive assessment of fatty liver combined with PreDM and MetS features screening might provide further accuracy in predicting hyperglycemic status in the clinical setting with the putative description of singular phenotypes. The objective of the study is to evaluate and describe the links of a widely available FLD surrogate -the non-invasive serological biomarker Hepatic Steatosis Index (HSI)- with previously described T2DM risk predictors, such as preDM and MetS in forecasting T2DM onset. PATIENTS AND METHODS: A retrospective ancillary cohort study was performed on 2799 patients recruited in the Vascular-Metabolic CUN cohort. The main outcome was the incidence of T2DM according to ADA criteria. MetS and PreDM were defined according to ATP III and ADA criteria, respectively. Hepatic steatosis index (HSI) with standardized thresholds was used to discriminate patients with FLD, which was referred as estimated FLD (eFLD). RESULTS: MetS and PreDM were more common in patients with eFLD as compared to those with an HSI < 36 points (35% vs 8% and 34% vs. 18%, respectively). Interestingly, eFLD showed clinical effect modification with MetS and PreDM in the prediction of T2DM [eFLD-MetS interaction HR = 4.48 (3.37-5.97) and eFLD-PreDM interaction HR = 6.34 (4.67-8.62)]. These findings supported the description of 5 different liver status-linked phenotypes with increasing risk of T2DM: Control group (1,5% of T2DM incidence), eFLD patients (4,4% of T2DM incidence), eFLD and MetS patients (10,6% of T2DM incidence), PreDM patients (11,1% of T2DM incidence) and eFLD and PreDM patients (28,2% of T2DM incidence). These phenotypes provided independent capacity of prediction of T2DM incidence after adjustment for age, sex, tobacco and alcohol consumption, obesity and number of SMet features with a c-Harrell=0.84. CONCLUSION: Estimated Fatty Liver Disease using HSI criteria (eFLD) interplay with MetS features and PreDM might help to discriminate patient risk of T2DM in the clinical setting through the description of independent metabolic risk phenotypes. [Correction added on 15 June 2023, after first online publication: The abstract section was updated in this current version.].

A Mediterranean lifestyle reduces the risk of cardiovascular disease in the "Seguimiento Universidad de Navarra" (SUN) cohort.

BACKGROUND AND AIMS: A healthy lifestyle is essential to prevent cardiovascular disease (CVD). However, beyond dietary habits, there is a scarcity of studies comprehensively assessing the typical traditional Mediterranean lifestyle with a multi-dimensional index. We assessed the association between the Mediterranean lifestyle (measured with the MEDLIFE index including diet, physical activity, and other lifestyle factors) and the incidence of CVD. METHODS AND RESULTS: The "Seguimiento Universidad de Navarra" (SUN) project is a prospective, dynamic and multipurpose cohort of Spanish university graduates. We calculated a MEDLIFE score, composed of 28 items on food consumption, dietary habits, physical activity, rest, social habits, and conviviality, for 18,631 participants by assigning 1 point for each typical Mediterranean lifestyle factor achieved, for a theoretically possible final score ranging from 0 to 28 points. During an average follow-up of 11.5 years, 172 CVD cases (myocardial infarction, stroke or cardiovascular death) were observed. An inverse association between the MEDLIFE score and the risk of primary cardiovascular events was observed, with multivariable-adjusted hazard ratio (HR) = 0.50; (95% confidence interval, 0.31-0.81) for the highest MEDLIFE scores (14-23 points) compared to the lowest scores (0-9 points), p (trend) = 0.004. CONCLUSION: A higher level of adherence to the Mediterranean lifestyle was significantly associated with a lower risk of CVD in a Spanish cohort. Public health strategies should promote the Mediterranean lifestyle to preserve cardiovascular health.

Risk of incident ischemic stroke according to the metabolic health and obesity states in the Vascular-Metabolic CUN cohort.

Background Whether obesity is a major risk factor for cardiovascular disease in the absence of metabolic comorbidities remains under debate. Indeed, some obese individuals may be at low risk of metabolic-related complications, while normal-weight individuals may not be "healthy." Aims To assess the incidence of ischemic stroke according to the metabolic health and obesity states of 5171 participants from the Vascular-Metabolic CUN cohort. Methods A Cox proportional-hazard analysis was conducted to estimate the hazard ratio and their 95% confidence interval of stroke according to the metabolic health and obesity states based on TyG index and Adult Treatment Panel-III criteria, during 9.1 years of follow-up. Results After 50,056.2 person-years of follow-up, 162 subjects developed an ischemic stroke (incidence rate 3.23 per 1000 person-years). Metabolically healthy obese subjects did not show greater risk of stroke, while metabolically unhealthy participants, obese and non-obese, had an increased risk of stroke, compared with healthy non-obese. The hazard ratios for the multivariable adjusted model were 1.55 (95% CI: 1.36-1.77) and 1.86 (95% CI: 1.57-2.21), respectively. Conclusions Metabolically unhealthy individuals exhibited a greater risk of ischemic stroke than metabolically healthy obese individuals.

Are all metabolically healthy individuals with obesity at the same risk of diabetes onset?

OBJECTIVE: To examine the risk of diabetes and the development of an unhealthy status according to metabolic health. To assess the effect of changes in metabolic health among participants with metabolically healthy obesity (MHO) on the risk of diabetes. METHODS: A total of 4,340 subjects were included. Unhealthy metabolic status was defined as having three or more risk factors of the Adult Treatment Panel-III criteria. A Cox proportional-hazard analysis was conducted to estimate the hazard ratio (HR) of developing diabetes across the change in the metabolic status of subjects with MHO. RESULTS: After 40,622 person-years of follow-up, the risk of becoming unhealthy was 1.53 times higher for participants with MHO, compared with lean or overweight healthy subjects. A greater risk of diabetes was found in MHO, but it was attributable to those who progressed to an unhealthier status over time: HR of 4.78 (95% CI: 3.38-6.78). The combination of being metabolically unhealthy and obesity heightened the risk of diabetes: HR of 10.09 (95% CI: 4.82-21.55). CONCLUSIONS: The increased risk of diabetes in MHO is attributed to the progression to an unhealthier state. "Healthy obesity" is not a permanent situation but a transitory state.

Association of triglycerides and new lipid markers with the incidence of hypertension in a Spanish cohort.

OBJECTIVE: Triglycerides and high-density lipoprotein cholesterol (HDL-C) are known to be risk factors for cardiovascular disease. However, there has been limited knowledge on the relationship between triglycerides and incident hypertension. The associations of incident hypertension with triglycerides and triglycerides-related indices such as triglycerides to HDL-C ratio (TG/HDL-C) and triglyceride-glucose index (TyG) were evaluated. METHODS: Data from 3637 participants from the Vascular Metabolic Clinica Universidad Navarra cohort were followed-up during a mean of 8.49 years. A Cox proportional hazard ratio with repeated measures analyses was performed to assess the risk of developing hypertension across the quintiles of triglycerides, TG/HDL-C ratio, and TyG index. RESULTS: The risk of developing hypertension was 47% and 73% greater for those in the fourth and fifth quintiles of triglycerides, after adjusting for age, sex, BMI, cigarette smoking, daily alcohol intake, lifestyle pattern, type 2 diabetes, antiaggregation therapy, low-density lipoprotein cholesterol, SBP, and DBP. In men, those in the top quintile of triglycerides, TG/HDL-C ratio or TyG index were two times more likely to develop hypertension than those in the bottom quintile. In women, the effect was attenuated although the risk of hypertension rose with increasing quintiles (P for trend <0.05). The results were consistent when analyses were restricted to those participants without diabetes and obesity at baseline. CONCLUSIONS: Our results evidenced the associations between triglycerides-related variables and incident hypertension independently of adiposity. This association was stronger than those observed for other commonly used lipid parameters or lipid ratios, such as the TC/HDL-C ratio. VIDEO ABSTRACT: : http://links.lww.com/HJH/A620.

TyG Index Change Is More Determinant for Forecasting Type 2 Diabetes Onset Than Weight Gain.

The risk of type 2 diabetes associated with obesity appears to be influenced by other metabolic abnormalities, and there is controversy about the harmless condition of the metabolically healthy obese (MHO) state. The aim of this study is to assess the risk of diabetes and the impact of changes in weight and in triglyceride-glucose index (TyG index), according to the metabolic health and obesity states.We analyzed prospective data of the Vascular Metabolic CUN cohort, a population-based study among a White European population (mean follow-up, 8.9 years). Incident diabetes was assessed in 1923 women and 3016 men with a mean age at baseline of 55.33 ±â€Š13.68 and 53.78 ±â€Š12.98 years old.A Cox proportional-hazard analysis was conducted to estimate the hazard ratio (HR) of diabetes on metabolically healthy nonobese (MHNO), metabolically healthy obese, metabolically unhealthy nonobese (MUNO), and metabolically unhealthy obese (MUO). A continuous standardized variable (z-score) was derived to compute the HR for diabetes per 1-SD increment in the body mass index (BMI) and the TyG index.MHO, MUNO, and MUO status were associated with the development of diabetes, HR of 2.26 (95% CI: 1.25-4.07), 3.04 (95% CI: 1.69-5.47), and 4.04 (95% CI: 2.14-7.63), respectively. MUNO individuals had 1.82 greater risk of diabetes compared to MHO subjects (95% CI: 1.04-3.22). The HRs for incident diabetes per 1-SD increment in BMI and TyG indexes were 1.23 (95% CI: 1.04-1.44) and 1.54 (95% CI: 1.40-1.68). The increase in BMI did not raise the risk of developing diabetes among metabolically unhealthy subjects, whereas increasing the TyG index significantly affect the risk in all metabolic health categories.Metabolic health is more important determinant for diabetes onset than weight gain. The increase in weight does not raise the risk of developing diabetes among metabolically unhealthy subjects.

Triglyceride-glucose index (TyG index) in comparison with fasting plasma glucose improved diabetes prediction in patients with normal fasting glucose: The Vascular-Metabolic CUN cohort.

AIMS: We evaluated the potential role of the triglyceride-glucose index (TyG index) as a predictor of diabetes in a White European cohort, and compared it to fasting plasma glucose (FPG) and triglycerides. METHODS: 4820 patients of the Vascular-Metabolic CUN cohort (VMCUN cohort) were examined and followed up for 8.84years (±4.39). We performed a Cox proportional hazard ratio with repeated-measures analyses to assess the risk of developing type 2 diabetes across quartiles of FPG, triglycerides and the TyG index (ln[fasting triglycerides (mg/dl)×fasting plasma glucose (mg/dl)/2]), and plotted a receiver operating characteristics (ROC) curve for discrimination. RESULTS: There were 332 incident cases of type 2 diabetes involving 43,197.32person-years of follow-up. We observed a progressively increased risk of diabetes in subjects with TyG index levels of 8.31 or more. Among those with normal fasting glucose at baseline, <100mg/dl, subjects with the TyG index in the fourth quartile were 6.87 times more likely to develop diabetes (95% CI, 2.76-16.85; P for trend<0.001), as compared with the bottom quartile. The areas under the ROC curves (95% CI) were 0.75 (0.70-0.81) for TyG index, 0.66 (0.60-0.72) for FPG and 0.71 (0.65-0.77) for TG, in subjects with normal fasting glucose (p=0.017). CONCLUSIONS: Our data suggest that the TyG index is useful for the early identification of individuals at risk of type 2 diabetes. The TyG index seems to be a better predictor than FPG or triglycerides of the potential development of type 2 diabetes in normoglycemic patients.

The TyG index may predict the development of cardiovascular events.

BACKGROUND: Cardiovascular disease (CVD) is the worldwide leading cause of morbidity and mortality. An early risk detection of apparently healthy people before CVD onset has clinical relevance in the prevention of cardiovascular events. We evaluated the association between the product of fasting plasma glucose and triglycerides (TyG index) and CVD. MATERIAL AND METHODS: A total of 5014 patients of the Vascular Metabolic CUN cohort (VMCUN cohort) were followed up during a median period of 10 years. We used a Cox proportional-hazard ratio with repeated measures to estimate the risk of incidence of CVD across quintiles of the TyG index, calculated as ln[fasting triglycerides (mg/dL) × fasting plasma glucose (mg(dL)/2], and plotted a receiver-operating characteristics (ROC) curve to compare a prediction model fitted on the variables used in the Framingham risk score, a new model containing the Framingham variables with the TyG index, and the risk of coronary heart disease. RESULTS: A higher level of TyG index was significantly associated with an increased risk of developing CVD independent of confounding factors with a value of 2·32 (95% CI: 1·65-3·26) for those in the highest quintile and 1·52 (95% CI: 1·07-2·16) for those in the fourth quintile. The areas under the curve (AUC) of the ROC plots were 0·708 (0·68-0·73) for the Framingham model and 0·719 (0·70-0·74) for the Framingham + TyG index model (P = 0·014). CONCLUSIONS: The TyG index, a simple measure reflecting insulin resistance, might be useful to early identify individuals at a high risk of developing a cardiovascular event.

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