Aims: Familial clustering of diabetes and nephropathy suggests that either common environmental or inherited mechanisms are important in developing diabetic nephropathy. If an inherited mechanism is important, the albumin excretion rate might be increased in those at future risk. This study aimed to determine whether people with a family history of diabetes or people with a family history of renal disease were most at risk.
Methods: In a two-by-two factorial study of urinary albumin in non-diabetic Polynesians, 90 people with a first degree relative (FDR) with end-stage renal failure (ESRF) and diabetes (group 1) were compared with 90 people with a FDR with non-diabetic ESRF (group 2), with 90 people with a FDR with diabetes but no known nephropathy (group 3) and 90 people with no known relatives with either diabetes or nephropathy (group 4). Groups were matched for ethnicity and age.
Results: Subjects with a family history of ESRF (groups 1 and 2) had an increased mean albumin-creatinine ratio (1.25 vs. 1.00 mg/mmol, P = 0.01), but in subjects with a family history of diabetes (groups 1 and 3), the mean ratios were not significantly different from those without a family history of diabetes (1.06 vs. 1.17 mg/mmol; P = 0.2). In those with a family history of nephropathy, fasting blood glucose and systolic blood pressure were increased, while fasting insulin and 2 h insulin concentrations were lower. A family history of diabetes was associated with an increased fasting blood glucose and 2-h blood glucose. By multiple linear regression, the mean systolic blood pressure (P = 0.02), the 2-h glucose concentration (P = 0.05), a family history of renal failure (P = 0.04), female sex (P = 0.0001) and the total cholesterol (P = 0.01) were each independently associated with microalbuminuria, while a family history of diabetes was not (P = 0.09).
Conclusions: These data suggest that among Polynesians there is no specific inherited tendency to diabetic nephropathy per se. The risk of nephropathy does not appear to be associated with the degree of familial risk of diabetes itself. Rather, the risk of diabetic nephropathy may be the result of a familial risk of nephropathy from any cause and is associated with diabetes through relative hypoinsulinaemia and hyperglycaemia.