Effect of the inflammation, chronic hyperglycemia, or malabsorption on the apolipoprotein A-IV concentration in type 1 diabetes mellitus and in diabetes secondary to chronic pancreatitis

Abstract

The metabolism of apolipoprotein (apo) A-IV in diabetes mellitus (DM) is poorly understood. Several factors, such as dietary fat intake, fat malabsorption, acute inflammation, and hormonal dysregulation can disturb the plasma apo A-IV concentration. We have compared the plasma apo A-IV concentrations in patients with type 1 DM and DM secondary to chronic pancreatitis to determine the effects of combinations of these factors. We examined 4 groups of male patients with chronic pancreatitis without diabetes (ND-CP) (n = 12), diabetes secondary to chronic pancreatitis and insulin-treated (CP-DM) (n = 32), type 1 diabetes (n = 25), and controls (n = 20). Plasma apo A-IV was significantly lower in the chronic pancreatitis patients (ND-CP and CP-DM) than in the other patients. Inflammatory proteins (fibrinogen, ceruloplasmin, and haptoglobin) were significantly elevated in the 2 chronic pancreatitis groups. The apo A-IV concentration was positively correlated with hemoglobin A 1c (HbA 1c) percentage in each group of diabetic patients (CP-DM, r = .35; P = .046; type 1 DM, r = .53; P = .010), in both groups of diabetic patients ( r = .472; P [lt ] .0001) and negatively correlated with ceruloplasmin concentration in each group of diabetic patients (CP-DM, r = [minus ].48; P = .0052; type 1 DM, r = [minus ].66; P = .003), in both groups of diabetic patients ( r = [minus ].561; P [lt ] .0001), and in the whole population ( r = [minus ].463; P [lt ] .0001). Apo A-IV was also negatively correlated with haptoglobin in type 1 DM patients ( r = [minus ].434; P = .0435), in the both groups of diabetic patients ( r = [minus ].349; P = .0154), and in the whole population ( r = [minus ].351; P = .0019). Multiple linear regression analysis revealed that only HbA 1c and ceruloplasmin were independent explanatory variables. Plasma apo A-IV is positively correlated with HbA 1c suggesting that hyperglycemia per se selectively affects apo A-IV metabolism. The correlation between the concentrations of inflammatory protein and apo A-IV suggest a link between chronic inflammation and apo A-IV synthesis or catabolism. As apo A-IV is involved in reverse cholesterol transport, its low level in CP-DM may contribute to the accelerated development of atherosclerosis in these patients.