Newly-diagnosed Disturbed Glucose Metabolism after TIA or Stroke

The prevalence of diabetes mellitus is increasing. Diabetes mellitus is an important risk factor for first stroke and stroke recurrence. Pre-diabetes is an intermediate metabolic state between normal glucose metabolism and diabetes mellitus and the prevalence of pre-diabetes is increasing as well. Pre-diabetes is a potential treatable risk factor, because it not only increases the risk of developing diabetes mellitus but also of cardiovascular diseases. With this thesis I have shown that more than 70% of the patients with a recent TIA or stroke without a history of diabetes had pre-diabetes or newly-diagnosed diabetes. Three tests are available to diagnose (pre-)diabetes: fasting plasma glucose, oral glucose tolerance test and glycosylated hemoglobin levels. Our study provides a rationale for the use of all three tests. Post-stroke hyperglycemia can be transient, reflecting an acute stress response, or persistent, representing undiagnosed disturbed glucose metabolism. It is important to differentiate between transient and persistent disturbed glucose metabolism and we developed a prediction model. Fasting plasma glucose, triglycerides and the use of cholesterol lowering drugs were the most important predictors. It remains unknown whether glucose-lowering drugs reduces the risk of recurrent stroke. In preparation of a phase III trial, we initiated a phase II trial (MAAS trial) to investigate the feasibility, safety and effects on glucose metabolism on glucose metabolism of glucose-lowering drugs. The results of this study are not known yet. Lastly we found an association between atherosclerosis and pre-diabetes and newly-diagnosed disturbed glucose metabolism after a TIA or ischemic stroke. This might be the underlying mechanism of the increased risk of recurrent stroke in these patients

Occurrence and predictors of persistent impaired glucose tolerance after acute ischemic stroke or transient ischemic attack

Background Impaired glucose tolerance is often present in patients with a transient ischemic attack (TIA) or ischemic stroke and doubles the risk of recurrent stroke. This impaired glucose tolerance can be transient, reflecting an acute stress response, or persistent, representing undiagnosed impaired glucose metabolism possibly requiring treatment. We aimed to assess the occurrence of persistent impaired glucose tolerance after a stroke or TIA and to develop a prediction model to identify patients at risk of persistent impaired glucose tolerance. Methods Patients admitted to the str

Metformin and sitAgliptin in patients with impAired glucose tolerance and a recent TIA or minor ischemic Stroke (MAAS): study protocol for a randomized controlled trial

Background: Impaired glucose tolerance is present in one third of patients with a TIA or ischemic stroke and is associated with a two-fold risk of recurrent stroke. Metformin improves glucose tolerance, but often leads to side effects. The aim of this study is to explore the feasibility, safety, and effects on glucose metabolism of metformin and sitagliptin in patients with TIA or minor ischemic stroke and impaired glucose tolerance. We will also assess whether a slow increase in metformin dose and better support and information on this treatment will reduce the incidence of side effects in these patients. Methods/Design: The Metformin and sitAgliptin in patients with impAired glucose tolerance and a recent TIA or minor ischemic Stroke trial (MAAS trial) is a phase II, multicenter, randomized, controlled, open-label trial with blinded outcome assessment. Non-diabetic patients (n = 100) with a recent (<6 months) TIA, amaurosis fugax or minor ischemic stroke (modified Rankin scale ≤ 3) and impaired glucose tolerance, defined as 2-hour post-load glucose levels between 7.8 and 11.0 mmol/L after repeated standard oral glucose tolerance test, will be included. Patients with renal or liver impairment, heart failure, chronic hypoxic lung disease stage III-IV, history of lactate acidosis or diabetic ketoacidosis, pregnancy or breastfeeding, pancreatitis and use of digoxin will be excluded. The patients will be randomly assigned in a 1:1:2 ratio to metformin, sitagliptin or "no treatment." Patients allocated to metformin will start with 500 mg twice daily, which will be slowly increased during a 6-week period to a twice daily dose of 1000 mg. Patients allocated to sitagliptin will be treated with a daily fixed dose of 100 mg. The study has been registered as NTR 3196 in The Netherlands Trial Register. Primary outcomes include percentage still on treatment, percentage of (serious) adverse events, and the baseline adjusted difference in 2-hour post-load glucose levels at 6 months. Discussion: This study will give more information about the feasibility and safety of metformin and sitagliptin as well as the effect on 2-hour post-load glucose levels at 6 months in patients with TIA or ischemic stroke and impaired glucose tolerance

Prediction of Persistent Impaired Glucose Tolerance in Patients with Minor Ischemic Stroke or Transient Ischemic Attack

Background: Impaired glucose tolerance (IGT) in patients with ischemic stroke can return to normal, reflecting an acute stress response, or persist. Persistent IGT is associated with an increased risk of recurrent stroke, other cardiovascular diseases and unfavorable outcome after stroke. We aim to validate our previously developed model to identify patients at risk of persistent IGT in an independent data set, and, if necessary, update the model. Methods: The validation data set consisted of 239 nondiabetic patients with a minor ischemic stroke or TIA and IGT in the acute phase (2-hour post-load glucose levels between 7.8 and 11.0 mmol/l). The outcome was persistent versus normalized IGT, based on repeated oral glucose tolerance test after a median of 46 days. The discriminative ability of the original model was assessed with the area under the ROC curve (AUC). The updated model was internally validated with bootstrap resampling and cross-validated in the development population of the original model. Results: One-hundred eighteen of 239 (49%) patients had persistent IGT. The original model, with the predictors age, current smoking, statin use, triglyceride, hypertension, history of cardiovascular diseases, body mass index (BMI), fasting plasma glucose performed poorly (AUC .60). The newly developed model included only BMI, hypertension, statin use, atrial fibrillation, 2-hour post-load glucose levels, HbA1c, large artery atherosclerosis, and predicted persistent IGT more accurately (internally validated AUC 0.66, externally validated AUC .71). Conclusions: This prediction model with simple clinical variables can be used to predict persistent IGT in patients with IGT directly after minor stroke or TIA, and may be useful to optimize secondary prevention by early identification of patients with disturbed glucose metabolism