Increasing insulin resistance ups risk for stroke, death
After a median follow-up of 5.6 years, 4% (4,201) of the study population had had a stroke.
“We clearly see an increased occurrence of first-time stroke in the group with the lowest eGDR, indicating worst insulin resistance, in comparison with the group with the highest eGDR, indicating less insulin resistance,” Dr. Zabala reported.
After adjustment for potential confounding factors, including age at baseline, gender, diabetes duration, among other variables, the risk for stroke was lowest in those with a high eGDR value and highest for those with a low eGDR value.
Using individuals with the lowest eGDR (less than 4 mg/kg per min) and thus greatest risk of stroke as the reference, adjusted hazard ratios (aHR) for first-time stroke were: 0.60, 0.68, and 0.77 for those with an eGDR of greater than 8, 6-8, and 4-6 mg/kg per min, respectively.
The corresponding values for risk of ischemic stroke were 0.55, 0.68, and 0.75. Regarding hemorrhagic stroke, there was no statistically significant correlation between eGDR levels and stroke occurrence. This was due to the small number of cases recorded.
As for all-cause and cardiovascular mortality, a similar pattern was seen, with higher rates of death linked to increasing insulin resistance. Adjusted hazard ratios according to increasing insulin resistance (decreasing eGDR scores) for all-cause death were 0.68, 0.75, and 0.82 and for cardiovascular mortality were 0.65, 0.75, and 0.82.
A sensitivity analysis, using BMI instead of waist circumference to calculate the eGDR, showed a similar pattern, and “interestingly, a correlation between eGDR levels and risk of hemorrhagic stroke.” Dr. Zabala said.
Limitations and take-homes
Of course, this is an observational cohort study, so no conclusions on causality can be made and there are no data on the use of anti-diabetic treatments specifically. But there are strengths such as covering almost all adults with T2D in Sweden and a relatively long-follow-up time.
The findings suggest that “eGDR, which may reflect insulin resistance may be a useful risk marker for stroke and death in people with type 2 diabetes,” said Dr. Zabala.
“You had a very large cohort, and that certainly makes your results very valid,” observed Peter Novodvorsky, MUDr. (Hons), PhD, MRCP, a consultant diabetologist in Trenčín, Slovakia.
Dr. Novodvorsky, who chaired the session, picked up on the lack of information about how many people were taking newer diabetes drugs, such as the glucagon-like peptide 1 receptor antagonists and sodium glucose-lowering transport 2 inhibitors.
“As we all know, these might have protective effects which are not necessarily related to the glucose lowering or insulin resistance-lowering” effects, so could have influenced the results. In terms of how practical the eGDR is for clinical practice, Dr. Zabala observed in a press release: “eGDR could be used to help T2D patients better understand and manage their risk of stroke and death.
“It could also be of importance in research. In this era of personalized medicine, better stratification of type 2 diabetes patients will help optimize clinical trials and further vital research into treatment, diagnosis, care and prevention.”
The research was a collaboration between the Karolinska Institutet, Gothenburg University and the Swedish National Diabetes Registry. Dr. Zabala and coauthors reported having no conflicts of interest.