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OBJECTIVE--Mannose-binding lectin (MBL) is an essential component of the acute-phase immune response and may thus play a role in the pathogenesis of type 1 diabetes and diabetic nephropathy. The serum concentration of MBL is mainly genetically determined, and elevated concentrations have been associated with both type 1 diabetes and diabetic nephropathy. Previous genetic studies have not been conclusive due to the small number of patients and polymorphisms studied. We investigated whether MBL2 polymorphisms are associated with type 1 diabetes or diabetic nephropathy and whether patients with nephropathy have elevated MBL concentrations as indicated previously. Furthermore, we studied the association between MBL2 polymorphisms and MBL concentration. RESEARCH DESIGN AND METHODS--We genotyped 20 MBL2 single nucleotide polymorphisms (SNPs) in a large, well-characterized Finnish case-control sample consisting of 1,297 patients with type 1 diabetes with or without nephropathy and 701 nondiabetic individuals. The serum concentration of MBL was available for 1,064 patients. RESULTS--We found that 19 SNPs were associated with the MBL concentration (P = 3 x [10.sup.81]-7 x [10.sup.-4]). MBL concentrations were higher in patients with macroalbuminuria compared with patients without nephropathy even when the patients were stratified by the MBL2 genotypic background in accordance with previous studies. However, no evidence of association between any of the SNPs or their haplotype combinations and type 1 diabetes or diabetic nephropathy was observed. CONCLUSIONS--Although most of the MBL2 SNPs studied were associated with the MBL concentration, no common variations (neither single SNPs nor their haplotype combinations) confer risk of type 1 diabetes or diabetic nephropathy., Diabetic nephropathy is a common and devastating long-term complication of diabetes, but its pathogenesis is poorly understood. Low-grade inflammation and complement activation may, however, play a role in the pathogenesis [...]

Oxidative stress has been suggested to contribute to the development of diabetic nephropathy. Manganese superoxide dismutase (MnSOD) protects the cells from oxidative damage by scavenging free radicals. The demand for antioxidants is increased by smoking, which could disturb the balance between antioxidants and radicals. The present study aimed to determine whether a valine/alanine polymorphism in MnSOD (V16A, rs4880), alone or in combination with smoking, can contribute to development of diabetic nephropathy in 1,510 Finnish and Swedish patients with type 1 diabetes. Overt diabetic nephropathy (n = 619) was defined as having an albumin excretion rate (AER) >200 µg/min or renal replacement therapy; incipient diabetic nephropathy was defined as having an AER of 20-200 µg/min (n = 336). The control subjects had diabetes duration of ≥ 20 years, without albuminuria (AER, The increased mortality in patients with type 1 diabetes is predominantly accounted for by a poor prognosis for patients with diabetic nephropathy, the major causes of death being cardiovascular disease [...]

The metabolic syndrome varies in prevalence among different populations. A common feature, however, is a steep increase in prevalence along with a decrease in glucose tolerance (1-2). We have shown [...]