Glucose Disposal Rate Research Articles

Asprosin: the potential player in combined double diabetes and hypothyroidism.

Double diabetes is a term used to describe people with type 1 diabetes who are overweight, show signs of insulin resistance, or have a family history of type 2 diabetes. Asprosin is a novel glucogenic adipokine; Asprosin regulates appetite and glucose metabolism. The study aimed to investigate the level of asprosin in people with double diabetes with and without hypothyroidism and its association with markers of insulin resistance. This case-control study was conducted in Iraq between March 2022 and January 2023. One hundred sixty participants were enrolled; the selected participants were classified into three age and sex-matched groups. The first group consisted of eighty healthy controls served as the control group. Of eighty participants with newly discovered DD, half (40) have DD alone, and 40 have both DD and hypothyroidism. Serum asprosin, insulin, thyroid, lipid profile, glucose, and glycated hemoglobin were measured. The estimated glucose disposal rate, triglyceride-glucose index, and HOMA-IR were calculated. Participants with double diabetes had significantly (p ≤ 0.001) greater circulation asprosin levels than subjects in the control group. Comparatively, to double diabetes participants without hypothyroidism, asprosin levels were also higher in double diabetes subjects with hypothyroidism (p ≤ 0.001), and the insulin resistance markers increased in a stepwise way across the asprosin quartiles (p ≤ 0.001). Asprosin significantly correlated with insulin resistance markers, eGDR, plasma glucose, HbA1C, triglycerides, HDL-C, and LDL-C. Elevated asprosin levels might be a potential biomarker for the alteration in glucose metabolism, insulin resistance, and double diabetes. It may be the missing link between metabolic and endocrine disorders.

Association of Insulin Resistance With Cardiovascular Disease and All-Cause Mortality in Type 1 Diabetes: Systematic Review and Meta-analysis.

The association of insulin resistance (IR) with cardiovascular disease (CVD) and all-cause mortality in type 1 diabetes (T1D) remains unclear. To investigate whether IR is associated with CVD and all-cause mortality among individuals with T1D. PubMed, Embase, and the Cochrane Library databases were searched from inception to 31 October 2023. Observational studies reporting the associations between IR, as calculated by the estimated glucose disposal rate (eGDR), and the risk of CVD and all-cause mortality in individuals with T1D were eligible for inclusion. Data from eight selected studies were extracted, pooled by random-effects models, and results are presented as hazard ratios (95% CIs). Eight studies involving 21,930 individuals were included, of which five studies involving 19,960 individuals with T1D reported the risk of CVD. During a median follow-up of 10 years, there were 2,149 cases of incident CVD. The pooled hazard ratio for composite CVD outcome per 1-unit increase in the eGDR index was 0.83 (95% CI 0.78-0.90, I2 = 58.9%). Five studies involving 19,403 individuals reported the risk of all-cause mortality. During a median follow-up of 10 years, 1,279 deaths were observed. The pooled hazard ratio for all-cause mortality per 1-unit increase in the eGDR index was 0.84 (95% CI 0.81-0.87, I2 = 0%). The small number of available studies restricted our ability to perform meta-regression analyses or more detailed subgroup analyses. IR, as calculated by the eGDR, may be an additional risk factor for CVD and all-cause mortality in T1D.

Intermuscular adipose tissue accumulation is associated with higher tissue sodium in healthy individuals.

High tissue sodium accumulation and intermuscular adipose tissue (IMAT) are associated with aging, type 2 diabetes, and chronic kidney disease. In this study, we aim to investigate whether high lower-extremity tissue sodium accumulation relates to IMAT quantity and whether systemic inflammatory mediators and adipocytokines contribute to such association. Tissue sodium content and IMAT accumulation (percentage of IMAT area to muscle area) were measured in 83 healthy individuals using sodium imaging (23Na-MRI) and proton (1H-MRI) imaging of the calf. Insulin sensitivity was assessed by glucose disposal rate (GDR) measured with the hyperinsulinemic-euglycemic clamp. Median (interquartile range) muscle and skin sodium contents were 16.6 (14.9, 19.0) and 12.6 (10.9, 16.7) mmol/L, respectively. Median IMAT was 3.69 (2.80, 5.37) %. In models adjusted for age, sex, BMI, GDR, adiponectin, and high-sensitivity C-reactive protein, increasing tissue sodium content was significantly associated with higher IMAT quantity (p = 0.018 and 0.032 for muscle and skin tissue sodium, respectively). In subgroup analysis stratified by sex, skin sodium was significantly associated with IMAT only among men. In interaction analysis, the association between skin sodium and IMAT was greater with increasing levels of high-sensitivity C-reactive protein and interleukin-6 (p for interaction = 0.022 and 0.006, respectively). Leg muscle and skin sodium are associated with IMAT quantity among healthy individuals. The relationship between skin sodium and IMAT may be mediated by systemic inflammation.

Association between estimated glucose disposal rate and subclinical coronary atherosclerosis

Background and aimsThe estimated glucose disposal rate (eGDR) is an easily accessible clinical parameter for assessing insulin resistance in patients with diabetes mellitus. In this study, we aimed to investigate the link between eGDR and subclinical coronary atherosclerosis in an asymptomatic middle-aged Korean population. Methods and resultsThis study involved 4004 subjects who underwent routine health checkups with coronary multidetector computed tomography (MDCT) at Asan Medical Center from 2007 to 2011, among whom 913 had a follow-up analysis through 2014. The eGDR was calculated using: 21.16 − (0.09 ∗ waist circumference [cm]) − (3.41 ∗ hypertension) − (0.55 ∗ glycated hemoglobin [%]). Patients were categorized into three groups according to the tertiles of eGDR. Subclinical coronary atherosclerosis was defined by significant coronary stenosis (≥50%), presence of plaques, coronary artery calcification (CAC) score, and its progression. As a result, a lower eGDR level was associated with higher prevalence of significant coronary stenosis, plaques, moderate to severe CAC, and CAC progression. Compared to other markers or risk scores, eGDR was superior to other biomarkers of insulin resistance but did not provide additional information beyond classic cardiovascular risk models like the Framingham Risk Score and Pooled Cohort Equations. ConclusionDecreased eGDR values were significantly associated with higher subclinical coronary atherosclerosis burdens in an asymptomatic middle-aged Korean population. However, its clinical implications remain uncertain due to its weaker performance compared to established cardiovascular risk models.

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

ObjectivePrevious 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.MethodsThis 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).ResultsThe 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.ConclusionsThe 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 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

BackgroundRecent 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.MethodThe 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.ResultsWe 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.ConclusionA 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.

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.

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. 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 < 4mg/kg/min groups. Cox proportional hazards model was used to estimate the associations of eGDR with mortality. A total of 4725 prediabetic adults, 60.12% men, mean age 48years 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 < 4mg/kg/min groups, respectively, compared with the reference group. There were 410 deaths (116 CVD-related) during a median follow-up of 107months in 4,332 participants without baseline CVD. The hazard ratios and 95%CI for the eGDR 6-7.99, 4-5.99, and < 4mg/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. 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.

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). 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. 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 (β=-0.13(-0.14-0.11, P< 0.001). However, TyG index and HOMA-IR showed no significant correlation to arterial stiffness. 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.

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

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. 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. 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. A metabolically healthy phenotype is associated with lower frequency of IFG, IGT, and IFG + IGT status across all body weight categories.

Estimated glucose disposal rate as a predictor of chronic complications in type 1 diabetes - a cross-sectional study

Estimated glucose disposal rate as a predictor of chronic complications in type 1 diabetes - a cross-sectional study

Insulin sensitivity estimates and their longitudinal association with coronary artery disease in type 1 diabetes. Does it matter?

BackgroundInsulin resistance and chronic kidney disease are both associated with increased coronary artery disease risk. Many formulae estimating glucose disposal rate in type 1 diabetes infer insulin sensitivity from clinical data. We compare associations and performance relative to traditional risk factors and kidney disease severity between three formulae estimating the glucose disposal rate and coronary artery disease in people with type 1 diabetes.MethodsThe baseline glucose disposal rate was estimated by three (Williams, Duca, and Januszewski) formulae in FinnDiane Study participants and related to subsequent incidence of coronary artery disease, by baseline kidney status.ResultsIn 3517 adults with type 1 diabetes, during median (IQR) 19.3 (14.6, 21.4) years, 539 (15.3%) experienced a coronary artery disease event, with higher rates with worsening baseline kidney status. Correlations between the three formulae estimating the glucose disposal rate were weak, but the lowest quartile of each formula was associated with higher incidence of coronary artery disease. Importantly, only the glucose disposal rate estimation by Williams showed a linear association with coronary artery disease risk in all analyses. Of the three formulae, Williams was the strongest predictor of coronary artery disease. Only age and diabetes duration were stronger predictors. The strength of associations between estimated glucose disposal rate and CAD incidence varied by formula and kidney status.ConclusionsIn type 1 diabetes, estimated glucose disposal rates are associated with subsequent coronary artery disease, modulated by kidney disease severity. Future research is merited regarding the clinical usefulness of estimating the glucose disposal rate as a coronary artery disease risk factor and potential therapeutic target.

Association Between Triglyceride-Glucose Index and Homeostasis Model Assessment for Insulin Resistance with Estimated Glucose Disposal Rate.

This cross-sectional study was aimed to compare insulin resistance, Triglyceride- Glucose (TyG) index, fatty liver index (FLI) and hepatic steatosis index (HSI), glycaemic and lipids among groups/quartiles based upon estimated Glucose Disposal Rate (eGDR) from August 2022 to December 2022 among 249 male participants. The eGDR results in (mg/kg/min) were divided into four quartiles as: Group-I: {<6.88, n = 62}, Group-II: {<6.88-9.45, n = 63}, Group-III: {9.46-10.39, n = 62}, and Group-IV: {>10.39, n = 62}. Fasting plasma glucose (FPG), HbA1c, low density lipoprotein (LDL), homeostasis model assessment for insulin-resistance (HOMAIR), and TyG index demonstrated significant worsening increase from high to low eGDR groups. Receiver operating curve (ROC) analysis to calculate area under curve (AUC) for diagnostic efficiency candidate indices for eGDR demonstrated highest AUC for FLI as AUC: 0.736 (95% CI: 0.669-0.803), p < 0.001, followed by FPG: AUC: 0.682 (95% CI: 0.606-0.757), HOMAIR: AUC: 0.670 (95% CI: 0.602-0.739), HSI: AUC: 0.660 (95% CI: 0.589-0.731), TyG index: 0.658 (95% CI: 0.583-0.732), and HbA1c: 0.639 (95% CI: 0.583-0.732). Glycaemic measures, lipid indices, insulin resistance and TyG index deteriorated with declining eGDR. Diagnostic performance as evaluated by AUC for eGDR was highest for FLI, followed by FPG, HOMAIR, HSI, TyG index, HbA1c, and triglycerides. Key Words: Triglyceride, Insulin, Glucose, Diabetes.

Comparative impact of Roux-en-Y gastric bypass, sleeve gastrectomy or diet alone on beta-cell function in insulin-treated type 2 diabetes patients.

Although bariatric surgery is an effective treatment for type 2 diabetes by inducing weight loss and augmenting gut hormone secretion, the immediate effect on beta-cell function itself remains to be elucidated in type 2 diabetes. Therefore, a prospective, randomized trial was performed in 30 patients with insulin-treated type 2 diabetes and a body mass index ≥ 35kg/m2. Patients were randomly assigned (1:1:1) to Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) in combination with protein-sparing modified fast (PSMF), or to PSMF alone. Eu- and hyperglycemic clamps were performed before and 3weeks after surgery and/or PSMF initiation. The primary outcome was the evolution of insulin sensitivity and beta-cell function after surgery, calculated using the composite measures of glucose disposal rate, insulin secretion rate, and disposition index (DI). Results revealed that markers of insulin sensitivity increased similarly in all arms (p = 0.43). A higher marker for maximal beta-cell function was observed when comparing SG to PSMF (p = 0.007). The DI showed a clear positive evolution after RYGB and SG, but not after PSMF alone. Altogether, these findings indicate that bariatric surgery results in an immediate beta-cell function recovery in insulin-treated type 2 diabetes.

Association of physical activity and sports participation with insulin resistance and non-alcoholic fatty liver disease in people with type 1 diabetes.

To evaluate the association between physical activity (PA) and sports participation with insulin resistance and non-alcoholic fatty liver disease (NAFLD) in people with type 1 diabetes (T1D). People with T1D from a secondary and tertiary care centre were included. Questionnaire-derived PA was expressed in metabolic equivalent of task hours per week (METh/week). Insulin sensitivity was calculated with the estimated glucose disposal rate (eGDR). NAFLD was assessed by transient elastography (TE). Multivariate linear and logistic regression models were conducted, adjusted for age, sex, diabetes duration and BMI. In total, 254 participants were included (men 56%, age 44 ± 14 years, diabetes duration 24 ± 14 years, median BMI 24.8 kg/m2), of which 150 participants underwent TE. Total PA (median 50.7 METh/week) was not significantly associated with insulin resistance (median eGDR 7.31 mg/kg/min) (beta -0.00, 95% CI -0.01 to 0.00) or with NAFLD (OR 1.00, 95% CI 0.99-1.01). Participating in sports was significantly associated with eGDR (beta 0.94, 95% CI 0.48-1.41) and with NAFLD (OR 0.21, 95% CI 0.08-0.56). In our T1D population, we could not find any dose-dependent association between PA, insulin resistance and NAFLD. People participating in sports had a lower degree of insulin resistance and lower odds for NAFLD.

Short, frequent, light-intensity walking activity improves postprandial vascular-inflammatory biomarkers in people with type 1 diabetes: The SIT-LESS randomized controlled trial.

To examine the effect of interrupting prolonged sitting with short, frequent, light-intensity activity on postprandial cardiovascular markers in people with type 1 diabetes (T1D). In a randomized crossover trial, 32 adults with T1D (mean ± SD age 28 ± 5 years, glycated haemoglobin 67.9 ± 12.6 mmol/mol, 17 women) completed two 7-h laboratory visits separated by >7 days. Participants either remained seated for 7 h (SIT) or interrupted sitting with 3-min bouts of self-paced walking at 30-min intervals commencing 1 h after each meal (SIT-LESS). Physical activity, insulin regimen, experimental start times, and meal consumption were standardized during each arm. Plasma levels of interleukin (IL)-1β, tumour necrosis factor (TNF)-α, plasminogen activator inhibitor (PAI)-1 and fibrinogen were sampled at baseline, 3.5 and 7 h, and assessed for within- and between-group effects using a repeated measures ANOVA. The estimated glucose disposal rate was used to determine the insulin resistance status. Vascular-inflammatory parameters were comparable between SIT and SIT-LESS at baseline (p > .05). TNF-α, IL-1β, PAI-1 and fibrinogen increased over time under SIT, whereas these rises were attenuated under SIT-LESS (p < .001). Specifically, over the 7 h under SIT, postprandial increases were detected in TNF-α, IL-1β, PAI-1 and fibrinogen (+67%, +49%, +49% and +62%, respectively; p < .001 for all). Conversely, the SIT-LESS group showed no change in IL-1β (-9%; p > .50), whereas reductions were observed in TNF-α, PAI-1 and fibrinogen (-22%, -42% and -44%, respectively; p < .001 for all). The intervention showed enhanced effects in insulin-resistant individuals with T1D. Interrupting prolonged sitting with light-intensity activity ameliorates postprandial increases in vascular-inflammatory markers in T1D. The trial was prospectively registered (ISRCTN13641847).

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.

The 13C glucose breath test accurately identifies insulin resistance in people with type 1 diabetes.

This study investigated whether the delta-over-baseline of exhaled 13CO2 (Δ13CO2), generated from a 13C glucose breath test (13C-GBT), measured insulin resistance (IR) in people with type 1 diabetes, using the hyperinsulinemic-euglycemic clamp (HEC) as reference method. Secondary objective was to compare the 13C-GBT with the estimated glucose disposal rate (eGDR). A 40 mU/m2/min HEC and two separate 13C-GBTs (euglycemic with insulin bolus and hyperglycemic without bolus) were consecutively performed in 44 adults with type 1 diabetes with varying body compositions. eGDR was calculated based on HbA1c, presence of hypertension and waist circumference. Mean M-value was 5.9 ± 3.1 mg/kg/min, mean euglycemic Δ13CO2 was 6.4 ± 2.1 δ‰, while median eGDR was 5.9 [4.3 - 9.8] mg/kg/min. The hyperglycemic Δ13CO2 did not correlate with the M-value, while the euglycemic Δ13CO2 and the M-value correlated strongly (r = 0.74, p < 0.001). Correlation between M-value and eGDR was more moderate (Spearman's rho = 0.63, p < 0.001). Linear regression showed an association between Δ13CO2 and M-value, adjusted for age, sex and HbA1c (adjusted R² = 0.52, B = 1.16, 95% CI 0.80 - 1.52, p < 0.001). The AUROC for Δ13CO2 to identify subjects with IR (M-value < 4.9 mg/kg/min) was 0.81 (95% CI 0.68 - 0.94, p < 0.001). The optimal cut-off for Δ13CO2 to identify subjects with IR was ≤ 5.8 δ‰. Under euglycemic conditions, the 13C-GBT accurately identified individuals with type 1 diabetes and concurrent IR, suggesting its potential as a valuable non-invasive index.

Glucose tolerance and insulin resistance/sensitivity associate with retinal layer characteristics: the LIFE-Adult-Study

Aims/hypothesisAs the prevalence of insulin resistance and glucose intolerance is increasing throughout the world, diabetes-induced eye diseases are a global health burden. We aim to identify distinct optical bands which are closely related to insulin and glucose metabolism, using non-invasive, high-resolution spectral domain optical coherence tomography (SD-OCT) in a large, population-based dataset.MethodsThe LIFE-Adult-Study randomly selected 10,000 participants from the population registry of Leipzig, Germany. Cross-sectional, standardised phenotyping included the assessment of various metabolic risk markers and ocular imaging, such as SD-OCT-derived thicknesses of ten optical bands of the retina. Global and Early Treatment Diabetic Retinopathy Study (ETDRS) subfield-specific optical retinal layer thicknesses were investigated in 7384 healthy eyes of 7384 participants from the LIFE-Adult-Study stratified by normal glucose tolerance, prediabetes (impaired fasting glucose and/or impaired glucose tolerance and/or HbA1c 5.7–6.4% [39–47 mmol/mol]) and diabetes. The association of optical retinal band characteristics with different indices of glucose tolerance (e.g. fasting glucose, area under the glucose curve), insulin resistance (e.g. HOMA2-IR, triglyceride glucose index), or insulin sensitivity (e.g. estimated glucose disposal rate [eGDR], Stumvoll metabolic clearance rate) was determined using multivariable linear regression analyses for the individual markers adjusted for age, sex and refraction. Various sensitivity analyses were performed to validate the observed findings.ResultsIn the study cohort, nine out of ten optical bands of the retina showed significant sex- and glucose tolerance-dependent differences in band thicknesses. Multivariable linear regression analyses revealed a significant, independent, and inverse association between markers of glucose intolerance and insulin resistance (e.g. HOMA2-IR) with the thickness of the optical bands representing the anatomical retinal outer nuclear layer (ONL, standardised β=−0.096; p<0.001 for HOMA2-IR) and myoid zone (MZ; β=−0.096; p<0.001 for HOMA2-IR) of the photoreceptors. Conversely, markers of insulin sensitivity (e.g. eGDR) positively and independently associated with ONL (β=0.090; p<0.001 for eGDR) and MZ (β=0.133; p<0.001 for eGDR) band thicknesses. These global associations were confirmed in ETDRS subfield-specific analyses. Sensitivity analyses further validated our findings when physical activity, neuroanatomical cell/tissue types and ETDRS subfield categories were investigated after stratifying the cohort by glucose homeostasis.Conclusions/interpretationAn impaired glucose homeostasis associates with a thinning of the optical bands of retinal ONL and photoreceptor MZ. Changes in ONL and MZ thicknesses might predict early metabolic retinal alterations in diabetes.Graphical

Interactive calculator to estimate insulin sensitivity in type 1 diabetes.

The gold standard for measuring insulin sensitivity (IS) is the hyperinsulinemic-euglycemic clamp, a time, costly, and labor-intensive research tool. A low insulin sensitivity is associated with a complication-risk in type 1 diabetes. Various formulae using clinical data have been developed and correlated with measured IS in type 1 diabetes. We consolidated multiple formulae into an online calculator (bit.ly/estimated-GDR), enabling comparison of IS and its probability of IS <4.45 mg/kg/min (low) or >6.50 mg/kg/min (high), as measured in a validation set of clamps in 104 adults with type 1 diabetes. Insulin sensitivity calculations using different formulae varied significantly, with correlations (R2) ranging 0.005-0.87 with agreement in detecting low and high glucose disposal rates in the range 49-93% and 89-100%, respectively. We demonstrate that although the calculated IS varies between formulae, their interpretation remains consistent. Our free online calculator offers a user-friendly tool for individual IS calculations and also offers efficient batch processing of data for research.

Abstract WP272: 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 &gt;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 5.0mg/kg/min (interquartile range, 4.2-5.6) and 7.6mg/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&lt;0.01) at 3 months and favorable (adjusted odds ratio, 1.55; 95% confidence interval, 1.24-1.93; P&lt;0.01) and excellent (adjusted odds ratio, 1.28; 95% confidence interval, 1.08-1.51; P&lt;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.