On stroke risk in type 2 diabetes : focus on glycemic control, insulin resistance, obesity and recovery

Background: People with type 2 diabetes (T2D) have an increased risk of cardiovascular disease. In this thesis the focus is on stroke with different aspects of aims, e.g. the risk of stroke in people with T2D, the role of glycemic control and insulin resistance (IR) in stroke, the potential intervention to minimize stroke damage, and the role of early-, and long-term outcome after carotid surgery in people with T2D.

Method: We used data from different Swedish national quality registries in conjunction with Swedish national health registries. With the use of Cox regression analysis, utilizing inverse probability of treatment weighting, we focused on the outcome of stroke and death in relation to T2D, glycemic control (HbA1c), estimated glucose disposal rate (eGDR), i.e. a proxy for IR, and after carotid intervention. In addition, we used a mouse model to evaluate the effect of IR on stroke recovery.

Results: There was a 50% relative increased risk of stroke and death in people with T2D compared to a matched general population. Glycemic control was independently associated with an increased risk of stroke and death (Study I). In people with T2D a low eGDR, i.e. high grade of IR, was associated with an increased stroke risk and death (Study II). Long-term dietary change led to weight loss with enhanced functional recovery after stroke. This effect was associated with pre-stroke normalization of fasting glucose and IR, and reduction of neuroinflammation together with enhancing neuroplasticity (Study III). After carotid surgery there was an increased early risk of stroke, but not for death, and in the long run there was an increased risk of stroke and death in people with T2D compared to people without diabetes (Study IV). Poor glycemic control (high HbA1c levels) in people with T2D have an increased long-term risk of stroke, and death after carotid surgery (Study V).

Conclusions: The thesis expands the knowledge on stroke risk in T2D. Its relationship to glycemic control, and IR supporting the evidence for adequate management of glycemic control and the need for assessing IR. It also demonstrates that intervention with reversal of IR improve stroke recovery in rodents, a further research aim in people. There is an increased early-, and long-term risk after carotid intervention in people with T2D supporting further studies to reduce that risk.

List of scientific papers

I. Zabala A, Darsalia V, Holzmann MJ, Franzén S, Svensson AM, Eliasson B, Patrone C, Nyström T, Jonsson M. Risk of first stroke in people with type 2 diabetes and its relation to glycaemic control: A nationwide observational study. Diabetes Obes Metab. 2020 Feb;22(2):182-190.
https://doi.org/10.1111/dom.13885

II. Zabala A, Darsalia V, Lind M, Svensson AM, Franzén S, Eliasson B, Patrone C, Jonsson M, Nyström T. Estimated glucose disposal rate and risk of stroke and mortality in type 2 diabetes: a nationwide cohort study. Cardiovasc Diabetol. 2021 Oct 6;20(1):202.
https://doi.org/10.1186/s12933-021-01394-4

III. Karampatsi D, Zabala A, Wilhelmsson U, Dekens D, Vercalsteren E, Larsson M, Nyström T, Pekny M, Patrone C, Darsalia V. Dietinduced weight loss in obese/diabetic mice normalizes glucose metabolism and promotes functional recovery after stroke. Cardiovasc Diabetol. 2021 Dec 22;20(1):240.
https://doi.org/10.1186/s12933-021-01426-z

IV. Zabala A, Gottsäter A, Lind M, Svensson AM, Eliasson B, Bertilsson R, Ekelund J, Nyström T, Jonsson M. Early and long-term prognosis in patients with and without type 2 diabetes after carotid intervention: a Swedish nationwide propensity score matched cohort study. Cardiovasc Diabetol. 2021 Apr 24;20(1):85.
https://doi.org/10.1186/s12933-021-01282-x

V. Zabala A, Gottsäter A, Lind M, Eliasson B, Bertilsson R, Ekelund J, Jonsson M, Nyström T. Glycemic control and outcome after carotid intervention in patients with T2D: A Swedish nationwide cohort study. Diab Vasc Dis Res. 2023 May-Jun;20(3):14791641231176767.
https://doi.org/10.1177/14791641231176767