Insulin resistance and arteriosclerosis obliterans in patients with NIDDM

OBJECTIVE - To investigate the risk factors for arteriosclerosis obliterans (ASO) in NIDDM, we measured insulin sensitivity and other risk factors including lipoprotein(a) [Lp(a)] in NIDDM patients with and without ASO. RESEARCH DESIGN AND METHODS - A case-control study in 100 patients with NIDDM, 35 with and 65 without ASO, was performed. Insulin sensitivity was assessed by the short insulin tolerance test's K index (K-ITT). Duration of diabetes, a history of smoking, prevalence of hypertension, prevalence of coronary artery disease (CAD), serum C-peptide, 24-h urinary C-peptide, serum lipids, and Lp(a) were compared in the two groups. RESULTS - Age, BMI, HbA(1c), and fasting plasma glucose were comparable in the two groups. Patients with ASO were significantly more insulin resistant than patients without ASO (K-ITT 2.16 +/- 0.16 vs. 3.00 +/- 0.13%/min, P < 0.0001, respectively), had a longer duration of diabetes (10.3 +/- 1.2 vs. 7.5 +/- 0.8 years, P < 0.05), included a greater number of smokers (68.6 vs. 40.0%, P < 0.01), had a higher prevalence of CAD (60.0 vs. 16.9%, P < 0.01), and had a greater percentage of insulin therapy (48.6 vs. 29.2%, P < 0.05). However, urinary and serum C-peptide levels, serum lipids, and Lp(a) levels were comparable in the two groups. Multiple logistic regression analysis indicated that a history of smoking (odds ratio 3.70, P = 0.011), insulin resistance (odds ratio 3.68, P < 0.001), and an elevated Lp(a) level (odds ratio 1.03, P = 0.020) were independently related to ASO. When patients with CAD were removed from the logistic regression analysis, insulin resistance was most strongly related to ASO (odds ratio 20.9, P < 0.001). CONCLUSIONS - Patients with ASO were characterized by a higher prevalence of CAD, a greater percentage of smokers, a greater percentage of insulin therapy, and a higher insulin resistance than were patients without ASO. Insulin resistance, especially, maybe the most powerfully related to ASO. Lp(a) may play a minor role in the development of ASO.