Acute myocardial infarction and glucose abnormalities : Novel risk markers and characteristics

Detta är en avhandling från Stockholm : Karolinska Institutet, Department of Medicine

Sammanfattning: Background: There is a strong relationship between abnormal glucose tolerance (AGT) and the occurrence of an acute myocardial infarction (AMI). The identification of novel risk markers and pathophysiological disease characteristics may add important information to our understanding of the reasons for the disease pattern and thereby open the door to new therapeutic opportunities in this high-risk group of patients. Aims: 1. To characterise patients with AMI and newly discovered AGT as regards their beta-cell function (Study I) 2. To investigate the long-term reliability of the early classification of glucose perturbations by means of an oral glucose tolerance test (OGTT) in patients with AMI without previously known glucose abnormalities (Study II) 3. To investigate the potential relationships between novel risk markers from the IGF-I system and the adipokines and future cardiovascular events and glucose tolerance in patients with AMI with and without glucose abnormalities (Studies III-V) Studies I-III and V: A total of 181 AMI patients (the GAMI study: 125 men, 56 women; mean age 63.5 ± 9.4 years) were enrolled and 168 of them were classified by means of an OGTT before hospital discharge as having normal glucose tolerance (NGT, n=55), impaired glucose tolerance (IGT, n=58) or type 2 diabetes (n=55). Classifications were repeated three and 12 months thereafter. Age- and gender-matched subjects from the background population served as controls (n=185, 127 men, 58 women; mean age 64.4 ± 9.2 years). Beta-cell function was quantified as the insulinogenic index (IGI) 30 minutes after the glucose load. The associations between levels of IGF-I, IGF binding proteins 1 and 3 (IGFBP-1, IGFBP-3), leptin, adiponectin, glucose metabolism and future cardiovascular events were studied. The studies revealed that patients with AMI and AGT have reduced beta-cell function compared with patients with AMI and NGT (Study I). These patients can be detected and reliably classified from a long-term perspective using an OGTT when they are discharged from the coronary care unit (Study II). Furthermore, patients with AMI and glucose abnormalities have lower levels of IGF-I compared with patients with NGT and controls (Study III). Moreover, high levels of leptin on the first morning after the AMI are associated with the presence of AGT at discharge and with a more serious long-term prognosis (Study V). Study IV: In the DIGAMI 2 trial, 1,253 patients with AMI and type 2 diabetes were randomised to one of three study arms receiving: a) a 24-hour insulin-glucose infusion followed by subcutaneous insulin-based, long-term glucose control, b) the same initial treatment followed by glucose-lowering treatment according to local practice or c) glucose-lowering treatment according to local practice. The main objective, to compare total mortality and morbidity between these management strategies, revealed no significant differences between the treatment groups regarding the primary (total mortality) or the secondary (mortality, non-fatal MI or stroke) endpoints. A total of 575 of the DIGAMI 2 patients participated in a biochemistry programme with repeated blood sampling during 12 months of follow-up. In these 575 patients, the associations between IGF-I, IGFBP-1 and future cardiovascular events were studied. A high level of IGFBP-1 at admission was a strong predictor of cardiovascular mortality and morbidity. Conclusion: Glucose abnormalities in patients with AMI without previously known type 2 diabetes are related to impaired beta-cell function. These patients can be detected with an OGTT as early as day 4-5 after the AMI and the classification of the glucometabolic state is reliable in a long-term perspective. Furthermore, low levels of IGF-I are related to glucose abnormalities, while high levels of leptin are related to both glucose abnormalities and the subsequent prognosis in AMI patients without previously known type 2 diabetes. Moreover, high levels of IGFBP-1 are related to morbidity and mortality in patients with AMI and established type 2 diabetes. These findings add important information and will hopefully lead to studies aimed at improving management strategies and risk assessments in these patient groups.

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