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.

Estimated glucose disposal rate as a candidate biomarker for thrombotic biomarkers in T1D: a pooled analysis

Purpose To determine the utility of estimated glucose disposal rate (eGDR) as a candidate biomarker for thrombotic biomarkers in patients with type 1 diabetes (T1D). Methods We reanalysed baseline pretreatment data in a subset of patients with T1D from two previous RCTs, consisting of a panel of thrombotic markers, including fibrinogen, tissue factor (TF) activity, and plasminogen-activator inhibitor (PAI)-1, and TNFα, and clinical factors (age, T1D duration, HbA1c, insulin requirements, BMI, blood pressure, and eGDR). We employed univariate linear regression models to investigate associations between clinical parameters and eGDR with thrombotic biomarkers. Results Thirty-two patients were included [mean ± SD age 31 ± 7 years, HbA1c of 58 ± 9 mmol/mol (7.5 ± 0.8%), eGDR 7.73 ± 2.61]. eGDR negatively associated with fibrinogen (P < 0.001), PAI-1 concentrations (P = 0.005), and TF activity (P = 0.020), but not TNFα levels (P = 0.881). We identified 2 clusters of patients displaying significantly different characteristics; 56% (n = 18) were categorised as ‘higher-risk’, eliciting significantly higher fibrinogen (+ 1514 ± 594 μg/mL; P < 0.001), TF activity (+ 59.23 ± 9.42 pmol/mL; P < 0.001), and PAI-1 (+ 8.48 ± 1.58 pmol/dL; P < 0.001), HbA1c concentrations (+ 14.20 ± 1.04 mmol/mol; P < 0.001), age (+ 7 ± 3 years; P < 0.001), duration of diabetes (15 ± 2 years; P < 0.001), BMI (+ 7.66 ± 2.61 kg/m2; P < 0.001), and lower mean eGDR (− 3.98 ± 1.07; P < 0.001). Conclusions Compared to BMI and insulin requirements, classical surrogates of insulin resistance, eGDR is a suitable and superior thrombotic risk indicator in T1D. Trial registration ISRCTN4081115; registered 27 June 2017.

Estimated glucose disposal rate demographics and clinical characteristics of young adults with type 1 diabetes mellitus: A cross-sectional pilot study

Background: Estimated glucose disposal rate (eGDR) is a practical measure of Insulin Resistance (IR) which can be easily incorporated into clinical practice. We profiled eGDR in younger adults with type 1 diabetes mellitus (T1DM) by their demographic and clinical characteristics. Methods: In this single centre study, medical records of TIDM were assessed and eGDR tertiles correlated with demographic and clinical variables. Results: Of 175 T1DM individuals, 108 (61.7%) were males. Mean age (±SD) was 22.0 ± 1.6 years and median time from diagnosis 11.0 years (range 1–23). Individuals were predominantly Caucasian (81.7%), with 27.4% being overweight (BMI: 25–30 kg/m2) and 13.7% obese (BMI > 30 kg/m2). Mean total cholesterol (TC) levels were significantly lower in high and middle eGDR tertiles (4.4 ± 1 and 4.3 ± 0.8 mmol/l, respectively) compared with low eGDR tertile (4.8 ± 1, p < 0.05 for both). Triglyceride (TG) levels showed a similar trend at 1.1 ± 0.5 and 1.1 ± 0.5 mmol/l for high and middle eGDR tertile compared to low eGDR tertile (1.5 ± 1 mmol/l, p < 0.05 for both). Renal function was similar across eGDR tertiles and no difference in retinopathy was detected. Conclusion: TC and TG are altered in individuals with T1DM and low eGDR, suggesting that this subgroup requires optimal lipid management to ameliorate their vascular risk.

The Precious Few Grams of Glucose During Exercise

As exercise intensity exceeds 65% of maximal oxygen uptake carbohydrate energy sources predominate. However, relative to the meager 4–5 g blood glucose pool size in a postabsorptive individual (0.9–1.0 g·L−1 × 5 L blood = 18–20 kcal), carbohydrate (CHO) oxidation rates of 20 kcal·min−1 can be sustained in a healthy and fit person for one hour, if not longer, all the while euglycemia is maintained. While glucose rate of appearance (i.e., production, Ra) from splanchnic sources in a postabsorptive person can rise 2–3 fold during exercise, working muscle and adipose tissue glucose uptake must be restricted while other energy substrates such as glycogen, lactate, and fatty acids are mobilized and utilized. If not for the use of alternative energy substrates hypoglycemia would occur in less than a minute during hard exercise because blood glucose disposal rate (Rd) could easily exceed glucose production (Ra) from hepatic glycogenolysis and gluconeogenesis. The goal of this paper is to present and discuss the integration of physiological, neuroendocrine, circulatory, and biochemical mechanisms necessary for maintenance of euglycemia during sustained hard physical exercise.

Utility of estimated glucose disposal rate for predicting metabolic syndrome in children and adolescents with type-1 diabetes

ObjectivesTo determine the clinical utility of the estimated glucose disposal rate (eGDR) for predicting metabolic syndrome (MetS) in children and adolescents with type-1 diabetes (T1D).MethodsModified criteria of the International Diabetes Federation were used to determine MetS in children and adolescents between 10 and 18 years of age with T1D. The eGDR, a validated marker of insulin sensitivity, was calculated in two different ways using either the waist-to-hip ratio (WHR) or waist circumference (WC). Receiver operating characteristic (ROC) curve analysis was performed to ascertain cut-off levels of the eGDR to predict MetS.ResultsA total of 200 patients (52% male) with T1D were enrolled in the study. The prevalence of MetS was 10.5% (n: 21). Lower eGDR levels, indicating greater insulin resistance, were found in T1D patients with MetS when compared to those without (6.41 ± 1.86 vs. 9.50 ± 1.34 mg/kg/min) (p < 0.001). An eGDRWHR cut-off of 8.44 mg/kg/min showed 85.7% sensitivity and 82.6% specificity, while an eGDRWC cut-off of 8.16 mg/kg/min showed 76.1% sensitivity and 92.1% specificity for MetS diagnosis. The diagnostic odds ratio was 28.6 (7.3–131.0) for the eGDRWHR cut-off and 37.7 (10.8–140.8) for the eGDRWC cut-off.ConclusionsThe eGDR is a mathematical formula that can be used in clinical practice to detect the existence of MetS in children and adolescents with T1D using only the WC, existence of hypertension, and hemoglobin A1c levels. An eGDR calculated using the WC could be a preferred choice due to its higher diagnostic performance.