The estimated glucose disposal rate (eGDR) may be a useful tool to identify persons with type 2 diabetes at risk of first-time stroke, according to an observational study presented at the annual meeting of the European Association for the Study of Diabetes (EASD). The eGDR score was also predictive of all-cause and cardiovascular disease mortality.

The study examined the association of insulin resistance (measured by eGDR) and the risk of first stroke and death due to cardiac or any other cause in 104,697 persons (mean age 63 years) with type 2 diabetes. Data was sourced from Swedish National Diabetes Registry (NDR), the Swedish Cause of Death register, the Swedish In-patient Care Diagnoses registry, and the Longitudinal Database for Health Insurance and Labour Market Studies (LISA) between 2005 and 2016. Patients with a history of stroke were not included in the study.

Three parameters were considered to calculate eGDR: waist circumference, hypertension and glycosylated hemoglobin  (HbA1c).

The formula applied was “eGDR (mg/kg/min) = 21.158 - (0.09 * WC) - (3.407 * HT) - (0.551 * HbA1c) [WC = waist circumference (cm), HT = hypertension (yes=1/no=0) and HbA1c = HbA1c (DCCT %)]”.

Based on the results, the patients were categorized into four groups: eGDR <4 mg/kg/min (denoting the highest level of IR), eGDR 4-6 mg/kg/min, eGDR 6-8 mg/kg/min and eGDR >8 mg/kg/min (denoting the lowest level of insulin resistance). The mean eGDR calculated for the entire group was 5.6 mg/kg per min.

Analysis of data revealed that the risk of stroke and death increased with increasing insulin resistance; 4201 first-time strokes had occurred at 5.6 years of follow-up amounting to 4% of the study population.

The hazard ratio for first-time stroke in patients with eGDR 4-6 was 0.77, while the hazard ratios in patients with eGDR of 6-8 and >8 were 0.68 and 0.60, respectively. The corresponding values for risk of ischemic stroke were 0.55, 0.68, and 0.75. No such association was observed for hemorrhagic stroke.

Similarly, decreasing eGDR scores were also found to be associated with higher mortality. The corresponding hazard ratios according to eGDR scores (4-6, 6-8 and >8) for all-cause deaths were 0.68, 0.75, and 0.82 and for cardiovascular mortality were 0.65, 0.75, and 0.82.

The relative risk was highest for hypertension (0.045) followed by glycemic status (A1c) (0.013) and waist circumference (0.006).

In this large study, the risk of first-time stroke in patients with type 2 diabetes was found to be highest for those with lowest eGDR scores evocative of highest insulin resistance. Conversely, the risk was lowest for those with highest eGDR scores indicating lowest insulin resistance.

There is enough evidence correlating insulin resistance with increased risk of stroke. This study has reiterated insulin resistance as a risk factor for stroke in type 2 diabetic patients. What is interesting about this study is how insulin resistance was assessed.

The euglycemic clamp method is the gold-standard technique to measure insulin resistance, which is a difficult and cumbersome technique. This study has considered eGDR as a surrogate marker of insulin resistance using three easily available clinical parameters such as waist circumference (BMI can be an alternate variable), hypertension and HbA1c, for the calculation and therefore can be done in day-to-day clinical practice. Measuring eGDR can help to individualize the risk of stroke or death in type 2 diabetes and initiate timely and appropriate treatment.

References

1. Insulin resistance and risk of first stroke in type 2 diabetes: a nationwide cohort study (Abstract OP 01-4).  EASD 57th Annual Meeting 2021. https://www.abstractsonline.com/pp8/#!/9330/presentation/688
2. Estimating insulin resistance may help predict stroke, death in T2D - Medscape - Oct 21, 2021.