Hypertension and nephropathy in diabetes mellitus: what is inherited and what is acquired?

Prolonged duration of diabetes mellitus, poor long term glycemic control and raised blood pressure have all been clearly related to the development of diabetic nephropathy. Evidence exists to suggest that a subset of individuals with diabetes have a genetic predisposition to diabetic nephropathy. Cases of diabetic nephropathy cluster in families and a parental history of hypertension is more common in patients with diabetic nephropathy. Current evidence suggests an important role for hypertension in the genetic susceptibility to diabetic nephropathy but the extent of this is unknown. While cellular and animal studies have generated a plethora of data regarding mechanisms involved in the role of hypertension and diabetic nephropathy, these are not helpful for drawing conclusions in humans. In the following review, we examine the available clinical, epidemiologic and family studies to assess the relationship between the development of hypertension and diabetic nephropathy in IDDM and NIDDM. We will demonstrate the differences in the epidemiology of hypertension in diabetes depending on the type of diabetes and thus, move the emphasis of nephropathy susceptibility away from hypertension per se. We hope to emphasize instead the homogeneity of nephropathy risk in both IDDM and NIDDM and also the idea that a common genetic susceptibility exists for all types of diabetes and is conditional on cumulative exposure to hyperglycemia. Regarding the interaction of hypertension and nephropathy in diabetes mellitus, any conclusions at this time about what is inherited and what is acquired must be regarded as speculative. However we will discuss some potential mechanisms of hypertension in the evolution of nephropathy and we will allude to the role for novel genetic studies in the search for nephropathy susceptibility gene(s).