Insulin resistance assessed by estimated glucose disposal rate and risk of incident cardiovascular diseases among individuals without diabetes: findings from a nationwide, population based, prospective cohort study.

BACKGROUND: Recent studies have suggested that insulin resistance (IR) contributes to the development of cardiovascular diseases (CVD), and the estimated glucose disposal rate (eGDR) is considered to be a reliable surrogate marker of IR. However, most existing evidence stems from studies involving diabetic patients, potentially overstating the effects of eGDR on CVD. Therefore, the primary objective of this study is to examine the relationship of eGDR with incidence of CVD in non-diabetic participants. METHOD: The current analysis included individuals from the China Health and Retirement Longitudinal Study (CHARLS) who were free of CVD and diabetes mellitus but had complete data on eGDR at baseline. The formula for calculating eGDR was as follows: eGDR (mg/kg/min) = 21.158 - (0.09 × WC) - (3.407 × hypertension) - (0.551 × HbA1c) [WC (cm), hypertension (yes = 1/no = 0), and HbA1c (%)]. The individuals were categorized into four subgroups according to the quartiles (Q) of eGDR. Crude incidence rate and hazard ratios (HRs) with 95% confidence intervals (CIs) were computed to investigate the association between eGDR and incident CVD, with the lowest quartile of eGDR (indicating the highest grade of insulin resistance) serving as the reference. Additionally, the multivariate adjusted restricted cubic spine (RCS) was employed to examine the dose-response relationship. RESULTS: We included 5512 participants in this study, with a mean age of 58.2 ± 8.8 years, and 54.1% were female. Over a median follow-up duration of 79.4 months, 1213 incident CVD cases, including 927 heart disease and 391 stroke, were recorded. The RCS curves demonstrated a significant and linear relationship between eGDR and all outcomes (all P for non-linearity > 0.05). After multivariate adjustment, the lower eGDR levels were founded to be significantly associated with a higher risk of CVD. Compared with participants with Q1 of eGDR, the HRs (95% CIs) for those with Q2 - 4 were 0.88 (0.76 - 1.02), 0.69 (0.58 - 0.82), and 0.66 (0.56 - 0.79). When assessed as a continuous variable, per 1.0-SD increase in eGDR was associated a 17% (HR: 0.83, 95% CI: 0.78 - 0.89) lower risk of CVD, with the subgroup analyses indicating that smoking status modified the association (P for interaction = 0.012). Moreover, the mediation analysis revealed that obesity partly mediated the association. Additionally, incorporating eGDR into the basic model considerably improve the predictive ability for CVD. CONCLUSION: A lower level of eGDR was found to be associated with increased risk of incident CVD among non-diabetic participants. This suggests that eGDR may serve as a promising and preferable predictor and intervention target for CVD.

Frequency of prediabetes in individuals with increased adiposity and metabolically healthy or unhealthy phenotypes.

AIMS: To utilize the estimated glucose disposal rate (eGDR) index of insulin sensitivity, which is based on readily available clinical variables, namely, waist circumference, hypertension and glycated haemoglobin, to discriminate between metabolically healthy and unhealthy phenotypes, and to determine the prevalence of prediabetic conditions. METHODS: Non-diabetic individuals (n = 2201) were stratified into quartiles of insulin sensitivity based on eGDR index. Individuals in the upper quartiles of eGDR were defined as having metabolically healthy normal weight (MHNW), metabolically healthy overweight (MHOW) or metabolically healthy obesity (MHO) according to their body mass index, while those in the lower quartiles were classified as having metabolically unhealthy normal weight (MUNW), metabolically unhealthy overweight (MUOW) and metabolically unhealthy obesity (MUO), respectively. RESULTS: The frequency of impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and IFG + IGT status was comparable among the MHNW, MHOW and MHO groups, while it increased from those with MUNW status towards those with MUOW and MUO status. As compared with participants with MHNW, the odds ratio of having IFG, IGT, or IFG + IGT was significantly higher in participants with MUOW and MUO but not in those with MUNW, MHOW and MHO, respectively. CONCLUSIONS: A metabolically healthy phenotype is associated with lower frequency of IFG, IGT, and IFG + IGT status across all body weight categories.

Insulin resistance estimated by estimated glucose disposal rate predicts outcomes in acute ischemic stroke patients.

BACKGROUND: Estimated glucose disposal rate (eGDR), a simple and noninvasive measure of insulin resistance, has been proven to be an independent risk factor for first-time stroke and all-cause mortality. In this study, we aimed to investigate the associations between eGDR and the stroke outcome in patients with first-time acute ischemic stroke (AIS). METHODS: We included first-time AIS patients with available data on eGDR in the China National Stroke Registry III (CNSR-III), and divided the subjects into lower eGDR group (eGDR ≤ 6 mg/kg/min) and higher eGDR group (eGDR > 6 mg/kg/min). The primary outcome was excellent functional outcome (modified Rankin Scale score 0-1) at 3 months. Secondary outcomes included stroke recurrence and favorable functional outcome (modified Rankin Scale score 0-2) at 3 months, and functional outcome and combined vascular event at one year. Univariate and multivariate analyses were performed to evaluate the association between eGDR and outcomes. RESULTS: A total of 6,271 patients with AIS were included in this study. The median values of eGDR in lower and higher eGDR group were 5.0 mg/kg/min (interquartile range, 4.2-5.6) and 7.6 mg/kg/min (interquartile range, 6.8-9.6), respectively. Patients with higher eGDR were significantly associated with higher incidence of excellent functional outcome (adjusted odds ratio, 1.24; 95% confidence interval, 1.06-1.45; P < 0.01) at 3 months and favorable (adjusted odds ratio, 1.55; 95% confidence interval, 1.24-1.93; P < 0.01) and excellent (adjusted odds ratio, 1.28; 95% confidence interval, 1.08-1.51; P < 0.01) functional outcome at one year. However, there was no significant difference in stroke recurrence between these two groups at 3 months (adjusted odds ratio, 0.81; 95% confidence interval, 0.61-1.06; P = 0.12) and one year (adjusted odds ratio, 0.91; 95% confidence interval, 0.73-1.14; P = 0.41). CONCLUSION: eGDR is a predictor of functional outcome in patients with AIS, independent of traditional cardiovascular predictors.

Estimated glucose disposal rate is associated with retinopathy and kidney disease in young people with type 1 diabetes: a nationwide observational study.

AIMS: The aim of this study was to investigate the association between estimated glucose disposal rate (eGDR), a proxy for insulin resistance, and retinopathy or kidney disease, i.e. micro-, or macroalbuminuria, in young individuals with type 1 diabetes (T1D). MATERIAL AND METHODS: Using data from the Swedish pediatric registry for diabetes (SweDiabKids) and the registry for adults (NDR), all individuals with T1D with a duration of diabetes of less than 10 years between 1998 and 2017 were included. We calculated the crude incidence rates with 95% confidence intervals (CIs) and used multivariable Cox regression to estimate crude and adjusted hazard ratios (HRs) for two cohorts: retinopathy cohort or kidney disease cohort, stratified by eGDR categories: < 4, 4 to 5.99, 6 to 7.99, and ≥ 8 mg/kg/min (reference). RESULTS: A total of 22 146 (10 289 retinopathy cohort, and 11 857 kidney disease cohort with an overlapping of 9575) children and adults with T1D (median age 21 years, female 42% and diabetes duration of 6 and 7 years, respectively for the cohorts) were studied. During a median follow-up of 4.8 years (IQR 2.6-7.7) there were 5040 (24.7%), 1909 (48.1%), 504 (52.3%) and 179 (57.6%) events for retinopathy in individuals with an eGDR ≥ 8, 7.99 to 6, 5.99 to 4, and < 4 mg/kg/min, respectively. Corresponding numbers for kidney disease was 1321 (6.5%), 526 (13.3%), 255 (26.8%) and 145 (46.6%). After multiple adjustments for different covariates, individuals with an eGDR 7.99 to 6, 5.99 to 4 and < 4 mg/kg/min, had an increased risk of retinopathy compared to those with an eGDR ≥ 8 mg/kg/min (adjusted HRs, 95% CIs) 1.29 (1.20 to 1.40); 1.50 (1.31 to 1.71) and 1.74 (1.41 to 2.14). Corresponding numbers for kidney disease was (adjusted HRs, 95% CIs) 1.30 (1.11 to 1.52); 1.58 (1.25 to 1.99) and 1.33 (0.95 to 1.86), respectively. CONCLUSIONS: eGDR, a proxy for insulin resistance, is associated with retinopathy and kidney disease in young adults with T1D. The risk of retinopathy increased with lower eGDR. The risk of kidney disease also increased with lower eGDR; however results show no association between the lowest eGDR and kidney disease. eGDR can be helpful to identify young T1D individuals at risk.

Insulin resistance is more frequent in type 1 diabetes patients with long disease duration.

AIMS: To investigate the clinical status of insulin resistance (IR) and its correlation with disease duration in patients with type 1 diabetes (T1D). MATERIALS AND METHODS: Cross-sectional data from a T1D cohort were obtained (n = 923). IR-related metabolic disorders including hypertension, obesity, and dyslipidemia were used as outcome variables to explore the cut-off point for estimated glucose disposal rate (eGDR) by restricted cubic spline (RCS) curve. Regression models were used for multivariate analysis of the clinical factors associated with IR. The correlation between the status of IR and diabetes duration was depicted with the RCS curve. RESULTS: IR-related metabolic disorders were observed in 39.4% of patients, with 9.1% meeting the criteria for metabolic syndrome. Specifically, patients with ≥10 years of T1D were more likely to have IR-related metabolic disorders (54.7% vs. 36.9%, p < 0.05). The presence of IR, defined as an eGDR ≤9.0 mg/kg/min, was observed in 42.2% of patients. Patients with IR had a longer diabetes duration (3.5 vs. 2.7, years, p = 0.003) and higher insulin dose (0.5 vs. 0.4, units per kg per day, p < 0.001). Moreover, the presence of IR showed a gradual increase during 10 years' disease duration and further analysis showed that diabetes duration ≥10 years was a key element behind the development of IR and IR-related metabolic disorders. CONCLUSIONS: The status of IR is common in T1D patients, especially in those with ≥10 years of disease duration. Therapies targeting balancing glycaemic control and IR are needed to decrease the future risk of cardiovascular diseases in T1D. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT03610984 (cohort study of patients with type 1 diabetes).

Impact of estimated glucose disposal rate for identifying prevalent ischemic heart disease: findings from a cross-sectional study.

BACKGROUND: Insulin resistance is one of the major mechanisms for cardiovascular events. Estimated glucose disposal rate(eGDR) has been demonstrated as a simple, accurate, and cost-effective estimator of insulin resistance. Our study aims to evaluate the correlation between eGDR and the prevalent IHD and assess the incremental value of eGDR for identifying prevalent IHD in the rural general population. METHODS: Our study enrolled 10,895 participants from a cross-sectional survey of a metabolic management program. The survey was conducted in the rural areas of southeastern China between October 2019 and April 2020. eGDR = 21.158 - (0.09 * waist circumference) - (3.407 * hypertension) - (0.551 * HbA1c). RESULTS: The prevalence of IHD was 4.20%. After adjusting for demographic, anthropometric, laboratory, and medical history covariates, each SD increase of eGDR brought a 25.9% risk reduction for prevalent IHD. After dividing eGDR into groups, the top group had a 58.9% risk reduction than the bottom group. Furthermore, smooth curve fitting demonstrated that the correlation between eGDR and prevalent IHD was linear in the whole range of eGDR. Additionally, AUC suggested that eGDR could significantly improve the identification of prevalent IHD by adding it to cardiovascular risk factors (0.703 vs. 0.711, P for comparison = 0.041). Finally, the category-free net reclassification index and integrated discrimination index also implicated the improvement from eGDR to identify prevalent IHD. CONCLUSION: Our data demonstrated a significant, negative, and linear correlation between eGDR and prevalent IHD. Our findings could suggest the potential usefulness of eGDR to improve the identification of prevalent IHD in the rural general population.

Estimated glucose disposal rate and risk of cardiovascular disease: evidence from the China Health and Retirement Longitudinal Study.

OBJECTIVES: Previous studies had reported that insulin resistance (assessed by estimated glucose disposal rate; eGDR) was associated with higher risk of cardiovascular events (CVD) in diabetes patients. The aim of present study was to investigate the potential association between eGDR and CVD in general population. METHODS: The China Health and Retirement Longitudinal Study with 8,267 individuals were included in analysis. Participants were divided into four subgroups according to eGDR quartile. Cox proportional hazards regression models were used to examine the associations of eGDR with CVD (stroke or cardiac events). RESULTS: During 6 years of follow-up, a total of 1,476 respondents experienced a CVD (494 stroke and 1,110 cardiac events). In multivariable-adjusted analyses, the corresponding hazard ratio (95% confidence intervals) for the highest eGDR versus lowest quartile of eGDR was 0.58(0.49-0.67) for CVD. Each 1-SD increase of eGDR was associated with 16% (HRs = 0.84; 0.79-0.88) decreased risk of CVD. There was also a significant linear association between eGDR and CVD (P for linearity < 0.001). Similar associations were also found between eGDR and stroke and cardiac events. CONCLUSION: A higher eGDR (a measure of insulin resistance) was associated with a decreased risk of CVD, stroke and cardiac events in general Chinese population, suggesting that eGDR could be considered as a preferential predictor and treatment target of CVD. Future well-designed prospective clinical studies are needed to verify our findings and to assess the effect of eGDR interventions in CVD prevention and therapy.

Insulin resistance, diabetic kidney disease, and all-cause mortality in individuals with type 2 diabetes: a prospective cohort study.

BACKGROUND: It is unclear whether insulin resistance (IR) contributes to excess mortality in patients with type 2 diabetes independent of diabetic kidney disease (DKD), which is strongly associated with IR and is a major risk factor for cardiovascular disease (CVD), the main cause of death in these individuals. We tested this hypothesis in patients with type 2 diabetes from the Renal Insufficiency And Cardiovascular Events Italian Multicentre Study. METHODS: This observational, prospective, cohort study enrolled 15,773 patients with type 2 diabetes attending 19 Italian Diabetes Clinics in 2006-2008. Insulin sensitivity was assessed as estimated glucose disposal rate (eGDR), which was validated against the euglycaemic-hyperinsulinemic clamp technique. Vital status on October 31, 2015, was retrieved for 15,656 patients (99.3%). Participants were stratified by eGDR tertiles from T1 (≥ 5.35 mg/kg/min) to T3 (≤ 4.14 mg/kg/min, highest IR). RESULTS: CVD risk profile was worse in T2 and T3 vs T1. eGDR tertiles were independently associated with micro- and macroalbuminuria and the albuminuric DKD phenotypes (albuminuria with preserved or reduced estimated glomerular filtration rate [eGFR]) as well as with eGFR categories or the nonalbuminuric DKD phenotype. Over a 7.4-year follow-up, unadjusted death rates and mortality risks increased progressively across eGDR tertiles, but remained significantly elevated after adjustment only in T3 vs T1 (age- and gender- adjusted death rate, 22.35 vs 16.74 per 1000 person-years, p < 0.0001, and hazard ratio [HR] adjusted for multiple confounders including DKD, 1.140 [95% confidence interval [CI], 1.049-1.238], p = 0.002). However, eGDR was independently associated with mortality in participants with no DKD (adjusted HR, 1.214 [95% CI, 1.072-1.375], p = 0.002) and in those with nonalbuminuric DKD (1.276 [1.034-1.575], p = 0.023), but not in those with the albuminuric DKD phenotypes. Moreover, the association was stronger in males and in younger individuals and was observed in those without but not with prior CVD, though interaction was significant only for age. CONCLUSIONS: The proxy of insulin sensitivity eGDR predicts all-cause mortality in type 2 diabetes, independent of confounders including DKD. However, the impact of IR in individuals with albuminuric DKD may be mediated by its relationship with albuminuria. TRIAL REGISTRATION: ClinicalTrials.gov , NCT00715481, retrospectively registered 15 July 2008.

Estimated glucose disposal rate and risk of stroke and mortality in type 2 diabetes: a nationwide cohort study.

BACKGROUND AND AIMS: Insulin resistance contributes to the development of type 2 diabetes (T2D) and is also a cardiovascular risk factor. The aim of this study was to investigate the potential association between insulin resistance measured by estimated glucose disposal rate (eGDR) and risk of stroke and mortality thereof in people with T2D. MATERIALS AND METHODS: Nationwide population based observational cohort study that included all T2D patients from the Swedish national diabetes registry between 2004 and 2016 with full data on eGDR and categorised as following: < 4, 4-6, 6-8, and ≥ 8 mg/kg/min. We calculated crude incidence rates and 95% confidence intervals (CIs) and used multiple Cox regression to estimate hazard ratios (HRs) to assess the association between the risk of stroke and death, according to the eGDR categories in which the lowest category < 4 (i.e., highest grade of insulin resistance), served as a reference. The relative importance attributed of each factor in the eGDR formula was measured by the R2 (± SE) values calculating the explainable log-likelihoods in the Cox regression. RESULTS: A total of 104 697 T2D individuals, 44.5% women, mean age of 63 years, were included. During a median follow up-time of 5.6 years, 4201 strokes occurred (4.0%). After multivariate adjustment the HRs (95% CI) for stroke in patients with eGDR categories between 4-6, 6-8 and > 8 were: 0.77 (0.69-0.87), 0.68 (0.58-0.80) and 0.60 (0.48-0.76), compared to the reference < 4. Corresponding numbers for the risk of death were: 0.82 (0.70-0.94), 0.75 (0.64-0.88) and 0.68 (0.53-0.89). The attributed relative risk R2 (± SE) for each variable in the eGDR formula and stroke was for: hypertension (0.045 ± 0.0024), HbA1c (0.013 ± 0.0014), and waist (0.006 ± 0.0009), respectively. CONCLUSION: A low eGDR (a measure of insulin resistance) is associated with an increased risk of stroke and death in individuals with T2D. The relative attributed risk was most important for hypertension.

Variants in HSD11B1 gene modulate susceptibility to diabetes kidney disease and to insulin resistance in type 1 diabetes.

BACKGROUND AND AIM: 11ß-Hydroxysteroid dehydrogenase 1 has been implicated in insulin resistance (IR) in the setting of metabolic disorders, and single nucleotide polymorphisms (SNPs) in its encoding gene (HSD11B1) have been associated with type 2 diabetes and metabolic syndrome. In type 1 diabetes (T1D), IR has been related to the development of chronic complications. We investigated the association of HSD11B1 SNPs with microvascular complications and with IR in a Brazilian cohort of T1D individuals. MATERIALS AND METHODS: Five SNPs were genotyped in 466 T1D individuals (57% women; median of 37 years old, diabetes duration of 25 years and HbA1c of 8.4%). RESULTS: The minor allele T of rs11799643 was nominally associated with diabetic retinopathy (OR = 0.52; confidence interval [CI] 95% = 0.28-0.96; P = .036). The minor allele C of rs17389016 was nominally associated with overt diabetic kidney disease (DKD) (OR = 1.90; CI 95% = 1.07-3.37; P = .028). A follow-up study revealed that 29% of the individuals lost ≥5 mL min-1 × 1.73 m2 per year of the estimated glomerular filtration rate (eGFR). In these individuals (eGFR decliners), C allele of rs17389016 was more frequent than in non-decliners (OR = 2.10; CI 95% = 1.14-3.89; P = .018). Finally, minor allele T of rs846906 associated with higher prevalence of arterial hypertension, higher body mass index and waist circumference, thus conferring risk to a lower estimated glucose disposal rate, a surrogate marker of insulin sensitivity (OR = 1.23; CI 95% = 1.06-1.42; P = .004). CONCLUSION: SNPs in the HSD11B1 gene may confer susceptibility to DKD and to IR in T1D individuals.

Insulin resistance is associated with preclinical carotid atherosclerosis in patients with type 1 diabetes.

AIM: Although insulin resistance (IR) is a growing trait among type 1 diabetes (T1D) population, its relationship with atherosclerosis has been scarcely studied. We assessed the association between IR indexes and carotid atherosclerosis in T1D, a population at high cardiovascular disease (CVD) risk. MATERIALS AND METHODS: We evaluated 191 participants with T1D and no prior CVD with at least one of the following criteria: ≥40 years old; diabetic nephropathy; or T1D duration ≥10 years harbouring ≥1 additional CVD risk factor. IR was assessed with the metabolic syndrome (MetS) harmonized definition proposed in 2009 and the estimated glucose disposal rate (eGDR), a T1D-specific IR surrogate marker (lower values indicating higher IR). Standardized carotid ultrasonography was performed, recording intima-media thickness (IMT), plaque presence and maximum height of plaque. Comparisons between patients according to their MetS status as well as concerning eGDR values were performed. RESULTS: The participants' median age was 47.4 (41.1-53.3) years and diabetes duration 25.7 (21.6-32.5) years. Plaque prevalence was higher in patients with greater IR (49.1%, 29.1% and 20%, P = .001, for any plaque according to decreasing eGDR tertiles). Conversely, no statistically significant higher plaque prevalence was found in participants with MetS. In multivariate analyses (adjusted for general- and T1D-specific risk factors, and statin treatment), MetS was associated with neither IMT nor plaque. On the contrary, eGDR was independently related to ≥2 plaques (P = .018) and maximum plaque height (P < .01). CONCLUSIONS: In T1D, IR assessed through eGDR but not by MetS definition was independently associated with plaque burden, a predictor of CVD.

Double diabetes: A distinct high-risk group?

The term double diabetes (DD) has been used to refer to individuals with type 1 diabetes (T1D) who are overweight, have a family history of type 2 diabetes and/or clinical features of insulin resistance. Several pieces of evidence indicate that individuals who display features of DD are at higher risk of developing future diabetes complications, independently of average glucose control, measured as glycated haemoglobin (HbA1c) concentration. Given the increased prevalence of individuals with features of DD, pragmatic criteria are urgently required to identify and stratify this group, which will help with subsequent implementation of more effective personalized interventions. In this review, we discuss the potential criteria for the clinical identification of individuals with DD, highlighting the strengths and weaknesses of each definition. We also cover potential mechanisms of DD and how these contribute to increased risk of diabetes complications. Special emphasis is placed on the role of estimated glucose disposal rate (eGDR) in the diagnosis of DD, which can be easily incorporated into clinical practice and is predictive of adverse clinical outcome. In addition to the identification of individuals with DD, eGDR has potential utility in monitoring response to different interventions. T1D is a more heterogeneous condition than initially envisaged, and those with features of DD represent a subgroup at higher risk of complications. Pragmatic criteria for the diagnosis of individuals with DD will help with risk stratification, allowing a more personalized and targeted management strategy to improve outcome and quality of life in this population.

Body composition and metabolic syndrome in patients with type 1 diabetes.

BACKGROUND: In recent years, the prevalence of obesity and metabolic syndrome in type 1 diabetes (T1DM) patients has gradually increased. Insulin resistance in T1DM deserves attention. It is necessary to clarify the relationship between body composition, metabolic syndrome and insulin resistance in T1DM to guide clinical treatment and intervention. AIM: To assess body composition (BC) in T1DM patients and evaluate the relationship between BC, metabolic syndrome (MS), and insulin resistance in these indi-viduals. METHODS: A total of 101 subjects with T1DM, aged 10 years or older, and with a disease duration of over 1 year were included. Bioelectrical impedance analysis using the Tsinghua-Tongfang BC Analyzer BCA-1B was employed to measure various BC parameters. Clinical and laboratory data were collected, and insulin resistance was calculated using the estimated glucose disposal rate (eGDR). RESULTS: MS was diagnosed in 16/101 patients (15.84%), overweight in 16/101 patients (15.84%), obesity in 4/101 (3.96%), hypertension in 34/101 (33.66%%) and dyslipidemia in 16/101 patients (15.84%). Visceral fat index (VFI) and trunk fat mass were significantly and negatively correlated with eGDR (both P < 0.001). Female patients exhibited higher body fat percentage and visceral fat ratio compared to male patients. Binary logistic regression analysis revealed that significant factors for MS included eGDR [P = 0.017, odds ratio (OR) = 0.109], VFI (P = 0.030, OR = 3.529), and a family history of diabetes (P = 0.004, OR = 0.228). Significant factors for hypertension included eGDR (P < 0.001, OR = 0.488) and skeletal muscle mass (P = 0.003, OR = 1.111). Significant factors for dyslipidemia included trunk fat mass (P = 0.033, OR = 1.202) and eGDR (P = 0.037, OR = 0.708). CONCLUSION: Visceral fat was found to be a superior predictor of MS compared to conventional measures such as body mass index and waist-to-hip ratio in Chinese individuals with T1DM. BC analysis, specifically identifying visceral fat (trunk fat), may play an important role in identifying the increased risk of MS in non-obese patients with T1DM.

Association between estimated glucose disposal rate and atrial fibrillation recurrence in patients undergoing radiofrequency catheter ablation: a retrospective study.

OBJECTIVE: Previous studies have shown a clear link between insulin resistance (IR) and an elevated risk of atrial fibrillation (AF). However, the relationship between the estimated glucose disposal rate (eGDR), which serves as a marker for IR, and the risk of AF recurrence after radiofrequency catheter ablation (RFCA) remains uncertain. Therefore, this study aimed to examine the potential association between the eGDR and the risk of AF recurrence following RFCA. METHODS: This retrospective study was conducted at Nanchang University Affiliated Second Hospital. The study enrolled 899 patients with AF who underwent RFCA between January 2015 and January 2022. The formula used to calculate the eGDR was as follows: 19.02 - (0.22 * body mass index) - (3.26 * hypertension) - (0.61 * HbA1c). Cox proportional hazard regression models and exposure-effect curves were used to explore the correlation between the baseline eGDR and AF recurrence. The ability of the eGDR to predict AF recurrence was evaluated using the area under the receiver operating characteristic curve (AUROC). RESULTS: The study observed a median follow-up period of 11.63 months, during which 296 patients experienced AF recurrence. K‒M analyses revealed that the cumulative incidence AF recurrence rate was significantly greater in the group with the lowest eGDR (log-rank p < 0.01). Participants with an eGDR ≥ 8 mg/kg/min had a lower risk of AF recurrence than those with an eGDR < 4 mg/kg/min, with a hazard ratio (HR) of 0.28 [95% confidence interval (CI) 0.18, 0.42]. Additionally, restricted cubic spline analyses demonstrated a linear association between the eGDR and AF recurrence (p nonlinear = 0.70). The area under the curve (AUC) for predicting AF recurrence using the eGDR was 0.75. CONCLUSIONS: The study revealed that a decrease in the eGDR is associated with a greater AF recurrence risk after RFCA. Hence, the eGDR could be used as a novel biomarker for assessing AF recurrence risk.

Insulin resistance and its relationship with long-term exposure to ozone: Data based on a national population cohort.

The relationship of ozone (O3), particularly the long-term exposure, with impacting metabolic homeostasis in population was understudied and under-recognised. Here, we used data from ChinaHEART, a nationwide, population-based cohort study, combined with O3 and PM2.5 concentration data with high spatiotemporal resolution, to explore the independent association of exposure to O3 with the prevalence of insulin resistance (IR). Among the 271 540 participants included, the crude prevalence of IR was 39.1%, while the age and sex standardized prevalence stood at 33.0%. Higher IR prevalence was observed with each increase of 10.0 µg/m3 in long-term O3 exposure, yielding adjusted odds ratios (OR) of 1.084 (95% CI: 1.079-1.089) in the one-pollutant model and 1.073 (95% CI: 1.067-1.079) in the two-pollutant model. Notably, a significant additive interaction between O3 and PM2.5 on the prevalence of IR was observed (P for additive interaction < 0.001). Our main findings remained consistent and robust in the sensitivity analyses. Our study suggests long-term exposure to O3 was independently and positively associated with prevalence of IR. It emphasized the benefits of policy interventions to reduce O3 and PM2.5 exposure jointly, which could ultimately alleviate the health and economic burden related to DM.

Estimated glucose disposal rate and risk of cardiovascular disease and mortality in U.S. adults with prediabetes: a nationwide cross-sectional and prospective cohort study.

AIMS: Estimated glucose disposal rate (eGDR), a noninvasive and convenient measure of insulin resistance, has been demonstrated to be associated with mortality in both type 1 and type 2 diabetes. We aimed to explore whether eGDR is associated with cardiovascular disease (CVD) risk and mortality in prediabetic adults. METHODS: A nationwide population-based cohort of prediabetic individuals from the National Health and Nutrition Examination Survey 1999-2018 with available data on eGDR was included and categorized into eGDR ≥ 8 (reference), 6-7.99, 4-5.99, and < 4 mg/kg/min groups. Cox proportional hazards model was used to estimate the associations of eGDR with mortality. RESULTS: A total of 4725 prediabetic adults, 60.12% men, mean age 48 years were included. The odds ratio and 95% confidence interval (CI) for CVD risk were 1.74 (1.08-2.78), 2.90 (1.79-4.67), and 4.58 (2.15-9.76) for the eGDR 6-7.99, 4-5.99, and < 4 mg/kg/min groups, respectively, compared with the reference group. There were 410 deaths (116 CVD-related) during a median follow-up of 107 months in 4,332 participants without baseline CVD. The hazard ratios and 95%CI for the eGDR 6-7.99, 4-5.99, and < 4 mg/kg/min groups were 1.70 (1.23-2.35), 2.01 (1.45-2.77), and 1.84 (1.11-3.04), respectively, for all-cause mortality (P for trend < 0.0001), and 3.84 (2.04-7.21), 4.01 (2.01-8.00), and 2.88 (1.03-8.06), respectively, for CVD mortality (P for trend = 0.01). Smoking status significantly modified the associations between eGDR and all-cause or CVD mortality. CONCLUSIONS: Increased insulin resistance, as indicated by a lower eGDR, is associated with increased risks of all-cause and CVD mortality in U.S. prediabetic adults.

Associations between estimated glucose disposal rate and arterial stiffness and mortality among US adults with non-alcoholic fatty liver disease.

Background: The estimated glucose disposal rate (eGDR), an effective indicator of insulin resistance, has been related to acute coronary syndrome, ischemic stroke and heart failure. This study aims to explore the relationship between eGDR and arterial stiffness, all-cause mortality and cardiovascular mortality in patients with non-alcoholic fatty liver disease (NAFLD). Methods: Participants with NAFLD were chosen from the National Health and Nutrition Examination Survey (NHANES) between 1999 and 2018. The main outcomes are arterial stiffness (represented by estimated pulse wave velocity, ePWV), all-cause and cardiovascular mortality. Multiple cox regression models, restricted cubic spline, sensitivity analysis and subgroup analysis were carried out to investigate the correlation between the insulin resistance indicators and mortality and arterial stiffness. Furthermore, receiver operating characteristic curves were used to compare the predictive value of the eGDR with the triglyceride-glucose (TyG) index and the homeostasis model assessment of insulin resistance (HOMA-IR) for all-cause and cardiovascular mortality. Results: In this study, a total of 4,861 participants were included for analysis. After adjusting confounding factors in the multivariate weighted cox regression model, the eGDR was inversely associated with the all-cause mortality (Q4 vs. Q1, HR =0.65 (0.48-0.89, P=0.01) and cardiovascular mortality (Q4 vs. Q1, HR =0.35 (0.19-0.65, P<0.001). Compared with TyG index and HOMA-IR, the eGDR shows excellent predictive value in all-cause mortality (0.588 vs. 0.550 vs. 0.513, P < 0.001) and cardiovascular mortality (0.625 vs. 0.553 vs. 0.537, P < 0.001). In addition, we found a significant negative correlation between eGDR and arterial stiffness (ß=-0.13(-0.14-0.11, P< 0.001). However, TyG index and HOMA-IR showed no significant correlation to arterial stiffness. Conclusions: Low eGDR (an indicator of insulin resistance) levels are related to an increased risk of arterial stiffness and mortality in NAFLD patients in the United States.

Comparison of Two Estimated Glucose Disposal Rate Methods for Detecting Insulin Resistance in Adults with Type 1 Diabetes Mellitus.

Background: The presence of insulin resistance (IR) in patients with type 1 diabetes mellitus (T1DM) is a significant indicator of all chronic diabetic complications, independent of other risk factors. The estimated glucose disposal rate (eGDR) is a practical method that can be easily used in daily practice to determine IR. This study aimed to determine the cutoff values for two eGDR methods and compare their diagnostic value for determining IR in adult T1DM patients with metabolic syndrome (MetS). Methods: This cross-sectional study was performed on 184 adults admitted to the endocrinology outpatient clinic diagnosed with T1DM. Demographic characteristics, anthropometric measurements, and the presence of hypertension (HT) were recorded. The eGDR of all patients was calculated using two formulas based on HbA1c level, presence of HT, waist-to-hip ratio (WHR), or waist circumference (WC). Diagnostic cutoff values for both eGDRs were defined using receiver operating characteristic (ROC) analysis. Patients were divided into two groups according to the cutoff values. The accuracy of the diagnostic cutoffs for eGDRwhr and eGDRwc was compared using a Bland-Altman plot. Results: The cutoff value for eGDRwhr was 7.37 mg/(kg·min) with 83.3% specificity and 86.7% sensitivity [area under the curve (AUC) = 0.901; P < 0.001; 95% confidence interval (CI), 0.824-0.977] and for eGDRwc 7.50 mg/(kg·min) with 79.8% specificity and 83.3% sensitivity (AUC = 0.895; P < 0.001; 95% CI, 0.817-0.972) for the presence of MetS. Further ROC analysis showed that the difference between the two AUCs (0.901 and 0.895) was not significant (P = 0.923). Conclusion: Assessment of eGDR would lead to early prevention of diabetic complications. eGDR is measured using either WHR or WC. This study is the first to compare WHR and WC in calculating eGDR in adults. WHR and WC are not superior to each other for calculating eGDR in determining IR in T1DM.

Estimated glucose disposal rate predicts the risk of diabetic peripheral neuropathy in type 2 diabetes: A 5-year follow-up study.

BACKGROUND: Insulin resistance is associated with chronic complications of diabetes, including diabetic peripheral neuropathy (DPN). Estimated glucose disposal rate (eGDR), calculated by the common available clinical factors, was proved to be an excellent tool to measure insulin resistance in large patient population. Few studies have explored the association between eGDR and DPN longitudinally. Therefore, we performed the current study to analyze whether eGDR could predict the risk of DPN. METHODS: In this prospective study, 366 type 2 diabetes (T2DM) subjects without DPN were enrolled from six communities in Shanghai in 2011-2014 and followed up until 2019-2020. Neuropathy was assessed by Michigan Neuropathy Screening Instrument (MSNI) at baseline and at the end of follow-up. FINDINGS: After 5.91 years, 198 of 366 participants progressed to DPN according to MNSI examination scores. The incidence of DPN in the low baseline eGDR (eGDR < 9.15) group was significantly higher than in the high baseline eGDR (eGDR ≥ 9.15) group (62.37% vs. 45.56%, p = .0013). The incidence of DPN was significantly higher in patients with sustained lower eGDR level (63.69%) compared with those with sustained higher eGDR level (35.80%). Subjects with low baseline eGDR (eGDR < 9.15) had significantly higher risk of DPN at the end of follow-up (odds ratio = 1.75), even after adjusting for other known DPN risk factors. CONCLUSIONS: The 5-year follow-up study highlights the importance of insulin resistance represented by eGDR in the development of DPN in T2DM. Diabetic patients with low eGDR are more prone to DPN and, therefore, require more intensive screening and more attention.

Value of estimated glucose disposal rate to detect prevalent left ventricular hypertrophy: implications from a general population.

BACKGROUND: Insulin resistance plays a pivotal role in developing left ventricular hypertrophy (LVH). Researchers have identified the estimated glucose disposal rate (eGDR) as a simple and cost-effective surrogate of insulin resistance. Our work aims to investigate the association between eGDR and the prevalent LVH and explore the incremental value of eGDR to detect prevalent LVH. METHODS: The present work enrolled 3839 subjects from a cross-sectional survey conducted between October 2019 to April 2020 in the rural areas of southeastern China. eGDR was calculated based on waist-to-hip circumference ratio, hypertension, and glycated hemoglobin. RESULTS: The prevalence of LVH was 17.30%. After adjusting demographic, anthropometric, laboratory, and medical history co-variates, each standard deviation increase of eGDR decreased a 29.6% risk of prevalent LVH. When dividing eGDR into quartiles, the top quartile had a 38.4% risk compared to the bottom quartile. Moreover, smooth curve fitting revealed that the association between eGDR and prevalent LVH was linear in the whole range of eGDR. Additionally, subgroup analysis demonstrated that our main finding was robust to age, sex, BMI, hypertension, and diabetes subgroups. Finally, ROC analysis exhibited a significant improvement by adding eGDR into LVH risk factors (0.780 vs. 0.803, P < 0.001), and category-free net reclassification index (0.702, P < 0.001) and integrated discrimination index (0.027, P < 0.001) also confirmed the improvement from eGDR to detect prevalent LVH. CONCLUSION: Our analysis revealed a linear, robust association between eGDR and prevalent LVH and demonstrated the incremental value of eGDR to optimize the detection of prevalent LVH.