Aspects of Abnormal Glucose Regulation in Various Manifestations of Coronary Artery Disease

Abstract: Background Diabetes is common among patients with coronary artery disease (CAD) and is associated with an approximate doubling of the mortality risk in this patient population. Prediabetes, an intermediate glycometabolic state between normal and diabetic glucose homeostasis, is also prevalent in patients with CAD but its prognostic impact has not been studied in detail. The optimal glucose-lowering treatment in CAD patients has been the subject of debate. Aims 1. To evaluate the association between admission glycaemia and future disturbance in glucose regulation, and mortality in patients with acute coronary syndrome (ACS). 2. To describe the association between diabetes and outcome after in-hospital cardiac arrest. 3. To evaluate the prevalence and the prognostic impact of abnormal glucose regulation after coronary artery bypass grafting (CABG). 4. To investigate whether increased mortality rates in insulin treated patients with type 2 diabetes and CAD can be explained by comorbidities. Study population This thesis is based on observational studies of four different study populations. To evaluate the association between admission glycaemia and future disturbance in glucose regulation (Study I) and mortality (Study II) we used data from the PRACSIS study comprising patients with ACS admitted to the coronary care unit at Sahlgrenska University Hospital, Gothenburg, between 1995 and 2001. Data on 1,810 patients, treated for in-hospital cardiac arrest between 1994 and 2006 at Sahlgrenska University Hospital and nine other hospitals in Sweden were used to analyse the association between diabetes and outcome (Study III). The prevalence and impact of abnormal glucose regulation were assessed in 276 patients undergoing CABG at Sahlgrenska University Hospital between 2003 and 2006 (Study IV). Data on 12,515 patients with type 2 diabetes undergoing coronary angiography between 2001 and 2009 were obtained from the NDR and the SCAAR registries and the association between glucose-lowering treatment and long-term mortality was analysed (Study V). Admission hyperglycaemia in patients with ACS In 762 ACS patients without known diabetes, the prevalence of diabetes at the 2.5 year follow-up increased with rising admission glucose, from 5% in those with plasma glucose of <6.1 mmol/l to 24% in those with plasma glucose of ≥7.0 mmol/l. Among 1,957 patients with ACS, admission hyperglycaemia defined as plasma glucose >9.4 mmol/l, was found to be an independent predictor of both 30-day mortality (HR 4.13, 95% CI: 2.54-6.70, p<0.0001) and late mortality (HR 1.57, 95% CI: 1.02-2.41, p=0.04) in patients without known diabetes. In patients with diabetes admission hyperglycaemia was an independent predictor of late mortality (HR 2.14, 95% CI: 1.21 to 3.78, p=0.009). Diabetes and survival after in-hospital cardiac arrest The in-hospital mortality rate was higher among patients with diabetes than among those without (70.7% vs 62.4%, p=0.001). The adjusted odds ratio of being discharged alive for patients with diabetes was 0.57 (95% CI: 0.40-0.79). Abnormal glucose regulation and prognosis after CABG Two-thirds (65%) of the patients undergoing CABG had either prediabetes or diabetes. During a mean follow-up period of 5.3 years there was a successive increase in the primary endpoint rate (a composite of all-cause mortality and hospitalisation for a cardiovascular event) from normoglycaemia through prediabetes to diabetes (adjusted HR 1.40; 95% CI, 1.01 to 1.96; p=0.045). Glucose-lowering treatment and prognosis Compared with diet treatment alone, insulin in combination with oral glucose-lowering treatment (adjusted HR 1.22; CI 1.06 to 1.40; p<0.005) and treatment with insulin alone (adjusted HR 1.17; CI 1.02 to 1.35; p<0.01) were independent predictors of long-term mortality in patients with type 2 diabetes undergoing coronary angiography. Conclusions These observational studies show that abnormal glucose regulation is prevalent and predicts a poor prognosis in patients with various manifestations of coronary artery disease. Not only patients with diabetes but also patients with acute phase hyperglycaemia and hyperglycaemia in the non-diabetic range appear to run an increased risk of unfavourable outcome. Treatment with insulin in type 2 diabetic patients undergoing coronary angiography predicts long-term mortality risk even after adjustment for comorbidities. Whether or not this association is causal remains to be clarified.