Levels of lipoprotein(a), apolipoprotein B, and lipoprotein cholesterol distribution in IDDM. Results from follow-up in the Diabetes Control and Complications Trial

Abstract

Levels of lipoprotein (a) [Lp(a)], apolipoprotein (apo) B, and lipoprotein cholesterol distribution using density-gradient ultracentrifugation were measured as part of a cross-sectional study at the final follow-up examination (mean 6.2 years) in the Diabetes Control and Complications Trial. Compared with the subjects in the conventionally treated group (n = 680), those subjects receiving intensive diabetes therapy (n = 667) had a lower level of Lp(a) (Caucasian subjects only, median 10.7 vs. 12.5 mg/dl, respectively; P = 0.03), lower apo B (mean 83 vs. 86 mg/dl, respectively; P = 0.01), and a more favorable distribution of cholesterol in the lipoprotein fractions as measured by density-gradient ultracentrifugation with less cholesterol in the very-low-density lipoprotein and the dense low-density lipoprotein fractions and greater cholesterol content of the more buoyant lowdensity lipoprotein. Compared with a nondiabetic Caucasian control group (n = 2,158), Lp(a) levels were not different in the intensive treatment group (median 9.6 vs. 10.7 mg/dl, respectively; NS) and higher in the conventional treatment group (9.6 vs. 12.5 mg/dl, respectively; P less than 0.01). No effect of renal dysfunction as measured by increasing albuminuria or reduced creatinine clearance on Lp(a) levels could be demonstrated in the diabetic subjects. Prospective follow-up of these subjects will determine whether these favorable lipoprotein differences in the intensive treatment group persist and whether they influence the onset of atherosclerosis in insulin-dependent diabetes. Lp(a) is formed by a molecule of a carbohydrate-rich protein named apo(a) linked by a single disulfide bond to the apo B of an LDL-like lipoprotein. Like LDL, Lp(a) is thought to be atherogeic. Because of the structural homology of apo(a) to plasminogen, it is also thought to have thrombogenic properties. This potential combination of proatherogenic and prothrombotic properties has led to a surge of research into the role of Lp(a) in atherosclerosis. KeywordsIn several case-controlled and prospective studies consisting primarily of white men with at least one preexisting cardiac risk factor, such as a family history of heart disease or an elevated LDL cholesterol level, an increased Lp(a) level has been shown to be an independent risk factor for CAD [5,10,11].Because up to 91 percent of the variability in plasma Lp(a) levels between individuals has been attributed to the apo(a) isoform [5,12], the contribution of age, sex, diet, and exercise to Lp(a) levels is thought to be small. Lp(a) levels have been shown to be higher in familial hypercholesterolemia [13], chronic renal failure [14][15][16][17][18][19], and nephrotic syndrome [20][21][22][23][24][25], and lower levels have been reported in cirrhosis [26]. How Lp(a) levels might be affected by IDDM and its complications and whether Lp(a) contributes to CAD [27,28] in this population remain controversial. Some investigators found elevated Lp(a) levels in subjects with IDDM compared with normoglycemic co...

Association of Insulin Dose, Cardiometabolic Risk Factors, and Cardiovascular Disease in Type 1 Diabetes During 30 Years of Follow-up in the DCCT/EDIC Study

“…insulin dose and LDL cholesterol levels are probably more complex. As previously reported, during the DCCT, participants assigned to intensive therapy showed a 34% reduction in LDL cholesterol levels, lower apolipoprotein B, lower cholesterol content of dense LDL and VLDL, and higher content of buoyant LDL compared with subjects in the conventional treatment group (25,26). These findings are consistent with data from metabolic studies in humans showing decreased levels of VLDL triglycerides and LDL cholesterol and increased HDL2 cholesterol levels, along with upregulation of adipose tissue lipoprotein lipase, following insulin therapy (27)(28)(29).…”

The impact of pancreas and kidney transplant on cardiovascular risk factors (analyzed by mode of immunosuppression and exocrine drainage)

“…This result is reassuring and consistent with reports from other centers with smaller series of patients (9)(10)(11). Furthermore, it is typical of the response one would expect to see with an improvement in glucose control in patients with type 1 diabetes (12). Cyclosporine was associated with a greater reduction in total cholesterol when compared with tacrolimus and mycophenolate, but there was no difference in serum TG between the two groups.…”

The effect of long‐term glycaemic control on serum lipoprotein(a) levels in patients with Type 2 diabetes mellitus

“…However, most of the latter studies have been cross‐sectional and only the short‐term ( ≤ 6 months) effect of improved glycaemic control on Lp(a) levels have been investigated. Recently, the Diabetes Control and Complications Trial demonstrated that Lp(a) levels were lower in the intensively treated patients with Type 1 diabetes mellitus compared with those in patients receiving conventional therapy[13]. The present study is a long‐term prospective study on the relationship between Lp(a) levels and glycaemic control in Korean patients with Type 2 diabetes mellitus.…”