Different patterns of insulin resistance in relatives of type 1 diabetic patients with retinopathy or nephropathy

OBJECTIVE- Insulin resistance may be a risk factor for diabetic microangiopathy, which may have a familial component. We carried out a family-based study to determine which components of the insulin resistance syndrome are associated with diabetic retinopathy and nephropathy in type 1 diabetes. RESEARCH DESIGN AND METHODS- The Genesis France-Belgium Study is a multicenter binational study designed to investigate the genetic factors involved in the microvascular complications of type 1 diabetes using a family-based design. Probands were type 1 diabetic patients with diabetic retinopathy (classified as background, preproliferative, or proliferative) and possibly diabetic nephropathy (absent, incipient, established, or advanced). The insulin resistance score of their first-degree relatives was calculated according to their BMI and history of arterial hypertension, lipid disorders, and type 2 diabetes. RESULTS- The insulin resistance score of relatives was positively correlated with the albumin excretion rate (P = 0.0009) and fasting plasma glucose (P = 0.0003) and HbA(1c) (P < 0.0001) concentrations. This score was higher in the relatives of probands with than in those without diabetic nephropathy (P = 0.0370). Similarly, it was higher in relatives of subjects with proliferative diabetic retinopathy than in those of probands without, even after controlling for subjects with versus without diabetic nephropathy (P = 0.0379). However, the components of the insulin resistance score in relatives differed according to the severity of diabetic retinopathy or nephropathy in the probands. Obesity and history of arterial hypertension were most common in relatives of probands with proliferative diabetic retinopathy, whereas obesity and history of lipid disorders were most common in the relatives of probands with diabetic nephropathy. CONCLUSIONS- Familial insulin resistance segregates with diabetic complications: lipid disorders and obesity segregate with diabetic nephropathy, whereas arterial hypertension and obesity segregate with diabetic retinopathy.