Decreased interstitial apolipoprotein A-I levels in IDDM patients with diabetic nephropathy

The risk of cardiovascular morbidity and mortality is highly increased in patients with diabetic nephropathy. Postulating that the generalized vasculopathy observed in these patients may enhance transcapillary filtration of lipids and lipoproteins resulting in a more atherogenic interstitial lipid profile, we set out to analyze the composition of their interstitial fluid. We studied healthy control subjects (n = 9), normoalbuminuric insulin-dependent diabetes mellitus (IDDM) patients (n = 16), and IDDM patients with diabetic nephropathy (n = 11) matched for age, body mass index, smoking habits, duration of diabetes, and metabolic control. Interstitial fluid was collected after an overnight fast by applying mild suction (200 mmHg) to the skin. Interstitial apolipoprotein A-I (apoA-I) levels were significantly lower in patients with nephropathy (0.18 +/- 0.10 milligram [mean +/- SD]) compared with normoalbuminuric diabetic patients (0.29 +/- 0.08 milligram) and healthy control subjects (0.30 +/- 0.09 milligram). Interstitial apolipoprotein B:apoA-I ratios tended to be higher in patients with diabetic nephropathy. In these patients, normal interstitial low-density lipoprotein cholesterol concentrations were observed in the presence of lower apoA-I levels. Transcapillary filtration of apoA-I was significantly lower in patients with diabetic nephropathy. Furthermore, an altered multiple regression model explaining interstitial apoA-I levels was observed in diabetic nephropathy. In this model, transcapillary protein (IgG) filtration and serum apoA-I levels no longer explained interstitial apoA-I levels. If we assume that interstitial apoA-I is involved in reverse cholesterol transport, these data suggest a more atherogenic interstitial lipoprotein profile in IDDM patients with nephropathy.