Lipoprotein(a) plasma levels are not associated with incident microvascular complications in type 2 diabetes mellitus

Abstract

Aims/hypothesis Microvascular disease in type 2 diabetes is a significant cause of end-stage renal disease, blindness and peripheral neuropathy. The strict control of known risk factors, e.g. lifestyle, hyperglycaemia, hypertension and dyslipidaemia, reduces the incidence of microvascular complications, but a residual risk remains. Lipoprotein (a) [Lp(a)] is a strong risk factor for macrovascular disease in the general population. We hypothesised that plasma Lp(a) levels and the LPA gene SNPs rs10455872 and rs3798220 are associated with the incident development of microvascular complications in type 2 diabetes. Methods Analyses were performed of data from the DiaGene study, a prospective study for complications of type 2 diabetes, collected in the city of Eindhoven, the Netherlands (n = 1886 individuals with type 2 diabetes, mean follow-up time = 6.97 years). To assess the relationship between plasma Lp(a) levels and the LPA SNPs with each newly developed microvascular complication (retinopathy n = 223, nephropathy n = 246, neuropathy n = 236), Cox proportional hazards models were applied and adjusted for risk factors for microvascular complications (age, sex, mean arterial pressure, non-HDL-cholesterol, HDL-cholesterol, BMI, duration of type 2 diabetes, HbA 1c and smoking). Results No significant associations of Lp(a) plasma levels and the LPA SNPs rs10455872 and rs3798220 with prevalent or incident microvascular complications in type 2 diabetes were found. In line with previous observations the LPA SNPs rs10455872 and rs3798220 did influence the plasma Lp(a) levels. Conclusions/interpretation Our data show no association between Lp(a) plasma levels and the LPA SNPs with known effect on Lp(a) plasma levels with the development of microvascular complications in type 2 diabetes. This indicates that Lp(a) does not play a major role in the development of microvascular complications. However, larger studies are needed to exclude minimal effects of Lp(a) on the development of microvascular complications.

Association Between Lipoprotein (A) and Diabetic Nephropathy in Patients With Type 2 Diabetes Mellitus: A Meta-Analysis

“…Of these, 16 were further excluded for the reasons listed in Figure 1 . Finally, eleven observational studies, including six prospective cohort studies ( 12 , 15 , 17 , 19 , 21 , 22 ), three cross-sectional studies ( 13 , 14 , 18 ), and two nested case-control studies ( 16 , 20 ), were included into the meta-analysis.…”

“…Overall, eleven studies with 9304 T2DM patients were included. The studies were performed in Korea ( 12 , 15 ), China ( 17 , 18 ), Japan ( 14 ), Iran ( 16 , 20 ), the United States ( 13 , 19 ), Denmark ( 21 ), and the Netherlands ( 22 ). The mean ages of the patients varied from 53 to 69 years.…”

“…The follow-up duration of the cohort studies varied from 2 to 11 years. In two studies, diabetic nephropathy was defined as the presence of microalbuminuria or macroalbuminuria ( 18 , 22 ); in seven studies, diabetic nephropathy was defined as the decline of renal function as evidenced by reduced eGFR or elevated SCr ( 12 , 13 , 15 – 17 , 19 , 21 ); while in the other two studies, a combined outcome of albuminuria and/or decline of renal function was used ( 14 , 20 ). Potential confounding factors, such as age, sex, smoking, body mass index, exercise, comorbidities, and use of antihypertensive medications, antidiabetic drugs, and lipid-lowering medications were adjusted to a varying degree.…”

“…Eight studies ( 13 – 17 , 19 , 20 , 22 ) evaluated the odds of diabetic nephropathy in T2DM patients with highest versus lowest serum Lp (a) levels. Pooled results with a random-effect model showed that patients with the highest Lp (a) level had higher odds of diabetic nephropathy (adjusted odds ratio [OR]: 1.63, 95% confidence interval [CI]: 1.25–2.14, I 2 = 54%, P <0.001; Figure 2A ).…”

“…Although early study has proposed that higher serum Lp (a) may also be associated with renal dysfunction in diabetic patients, subsequent studies evaluating the association between Lp (a) and diabetic nephropathy showed inconsistent results (10,11). Some studies suggested that serum Lp (a) is related to higher odds of diabetic nephropathy in T2DM patients (12)(13)(14)(15)(16)(17), while others did not (18)(19)(20)(21)(22). Therefore, relationship between Lp (a) level and diabetic nephropathy remains undetermined.…”