Midtveisevaluering - Iren Drange Hjellestad

Abstrakt

PERIPHERAL ARTERIAL DISEASE AND BIOMARKERS OF ABNORMAL GLUCOSE METABOLISM

A prospective study on HbA_1c, fasting plasma glucose and the oral glucose tolerance test, and the clinical importance of these biomarkers in patients with peripheral arterial disease

PhD candidate:  Iren D. Hjellestad
Main supervisor: Prof. Torbjørn Jonung
Co-supervisors: PhD in Endocrinology Eirik Søfteland, Prof. Eystein Husebye
Protocol identifying number: REK vest 14109.

Background
Peripheral arterial disease (PAD) and diabetes mellitus (DM) represent a major public health challenge. Patients with PAD have high mortality and morbidity. A strong association between DM and PAD has previously been established. Patients with PAD and DM have increased risk of amputations compared with patients with PAD alone. In general populations, 1/3 of patients with DM are unaware of their DM diagnose, and are therefore untreated and at high risk of developing complications. Former studies on AAA have, surprisingly, suggested a protective role of DM against development of AAA. Furthermore, studies have reported inconsistent results on long-term survival for patients with AAA with and without DM.

To improve DM diagnostics, HbA_1c has been implemented as a new diagnostic tool for DM. We therefore investigated the impact of HbA_1c on the association between DM and PAD, as well as its influence on clinical outcome.

Aims and methods
The study is a prospective cohort study on 345 patients with PAD admitted to Haukeland University Hospital for vascular surgery. The vascular pathologies were carotid stenosis, inguinal occlusive disease, infrainguinal occlusive disease and abdominal aortic aneurysm (AAA). Sixty-seven patients had known DM, while 275 patients without known DM were tested using the oral glucose tolerance test (OGTT) and HbA_1c. The main objectives was to validate HbA_1c against the OGTT, the current gold standard for diagnosis of DM; moreover to determine the ability of these tests to predict all-cause mortality, limb amputation and the need of surgical interventions due to relapse of vascular pathology. Mean follow-up time was 9.4 years. A sub-analysis on long-term mortality in 58 AAA patients without known DM was performed at 68 months of follow-up.

Results
OGTT revealed that 33 of 275 patients had DM, 90 had prediabetes (impaired fasting glucose and/or impaired glucose tolerance), and 152 had normal glucose metabolism. HbA_1c ≥ 6.5% detected DM with a 45.5 % sensitivity and a 90% specificity compared with the OGTT. The total prevalence of DM and prediabetes was 85 % based on HbA_1c values and 45 % based on OGTT results. All-cause mortality in the AAA group was 43 %. In AAA patients without previous DM, HbA_1c was an independent predictor for mortality. Hazard ratio of all-cause mortality in the DM category defined by HbA_1c values was 6.92, 95% [CI 1.63 – 29.4]; p = 0.009. According to OGTT results, patients with prediabetes had significantly higher mortality rate in crude analysis, HR 2.83, 95 % [CI 1.63 – 29.4]; p = 0.02. This association did not achieve statistical significance after multivariate analysis HR 2.28 95 % [CI 1.63 – 29.4]; p = 0.10.

Conclusion
OGTT and HbA_1c identify different groups of patients with DM. DM defined by HbA_1c is an important determinant of mortality following surgical treatment for AAA. We now plan to evaluate whether the OGTT or HbA_1c best to predict mortality and future relapse of the vascular disease in patients with PAD.