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Increased plasma apolipoprotein (a) levels in IDDM patients with diabetic nephropathy
L Tarnow1, P Rossing, F S Nielsen
1Steno Diabetes Center, Gentofte, Denmark.
Insights
Diabetic nephropathy significantly increases cardiovascular disease (CVD) risk. Elevated levels of apolipoprotein (a) [apo(a)] and dyslipidemia are key contributors to this heightened CVD risk in patients with type 1 diabetes.
Area of Science:
- Endocrinology and Metabolism
- Cardiovascular Research
- Nephrology
Background:
- Patients with insulin-dependent diabetes mellitus (IDDM) and diabetic nephropathy face a substantially higher risk of cardiovascular disease (CVD) mortality.
- Dyslipidemia, particularly elevated serum apolipoprotein (a) [apo(a)], is investigated as a potential contributor to this increased CVD risk.
Purpose of the Study:
- To assess the role of dyslipidemia and elevated apo(a) in the heightened CVD risk observed in IDDM patients with diabetic nephropathy.
Main Methods:
- A comparative study involving 199 IDDM patients with diabetic nephropathy and 192 normoalbuminuric IDDM patients.
- Analysis included measurements of CVD prevalence, serum apo(a) levels, and other lipid parameters (apoB, total cholesterol, triglycerides).
Main Results:
- CVD prevalence was significantly higher in patients with nephropathy (30%) compared to those without (12%).
- Elevated apo(a) levels (> 300 U/l) were more common in nephropathic patients (38%) and associated with CVD presence.
- Nephropathic patients exhibited higher levels of apoB, total cholesterol, and triglycerides. Apo(a) > 300 U/l was identified as an independent risk factor for coronary heart disease.
Conclusions:
- Dyslipidemia and elevated plasma apo(a) concentrations (> 300 U/l) likely contribute to the increased CVD morbidity and mortality in IDDM patients with diabetic nephropathy.
- These findings highlight the importance of managing lipid profiles and apo(a) levels in this patient population.
Objective:
The relative mortality from cardiovascular disease (CVD) is increased 40-fold in IDDM patients suffering from diabetic nephropathy as compared with nondiabetic subjects on average. We assessed the potential contribution of dyslipidemia in general and elevated serum apolipoprotein (a) [apo(a)] in particular to CVD in nephropathic patients with IDDM.
Research Design And Methods:
We investigated 199 IDDM patients with diabetic nephropathy and 192 normoalbuminuric IDDM patients matched for sex, age, diabetes duration, and BMI.
Results:
The prevalence of CVD was 30 and 12% in patients with and without nephropathy, respectively (P < 0.001). The level of apo(a) was significantly higher in patients with nephropathy, 189 (20-2,350) U/l as compared with the normoalbuminuric group, 103 (20-1,940) U/l (P < 0.005). The prevalence of plasma apo(a) > 300 U/l (at-risk level for cardiovascular pathogenicity) was 38% (31-45) vs. 22% (16-28) in patients with and without nephropathy, respectively (P < 0.0005). In nephropathic patients, the prevalence of plasma apo(a) > 300 U/l was raised in patients with CVD (48%, 36-61%) as compared with patients without (34%, 26-42%) (P = 0.05). Furthermore, the serum concentrations of the following apolipoproteins and lipids were higher in patients with nephropathy as compared with normoalbuminuric patients: apoB 1.33 +/- 0.37 vs. 1.06 +/- 0.26 g/l; total cholesterol 5.6 +/- 1.2 vs. 4.8 +/- 0.9 mmol/l; and triglycerides 1.22 (0.31-9.87) vs. 0.77 (0.28-3.05) mmol/l, P < 0.0001. Multiple logistic regression analysis of cardiovascular risk factors revealed that plasma apo(a) concentration > 300 U/l is an independent risk factor for coronary heart disease, odds ratio 1.86 (1.03-3.36) (P < 0.05).
Conclusions:
Dyslipidemia and raised plasma concentrations of apo(a), particularly > 300 U/l, may contribute to the enhanced morbidity and mortality from CVD characteristically observed in IDDM patients with diabetic nephropathy.