PATHOLOGICAL CONDITION

Pathological condition

PATHOLOGICAL CONDITION

Introduction

Diabetes has become the single most frequent comorbid condition in patients admitted for renal replacement therapy. This is the result of a greater prevalence of type 2 diabetes and better survival of diabetic patients. Progress has been made in pinpointing the predisposition to diabetes on metabolic abnormalities of muscle mitochondrial metabolism, but the long sought genes predisposing to diabetes and to diabetic nephropathy have not yet been identified.

Of great concern are experimental studies documenting that maternal hyperglycemia cause's nephron under dosing in the offspring. Relevant to pathogenesis and treatment of diabetic nephropathy are, among others, recent insights that hyperglycemia sensitizes target organs to blood pressure-induced damage, and that local renin-angiotensin systems play an important role in genesis and progression of diabetic nephropathy.

Discussion

Diabetic nephropathy has become the single most frequent condition causing end-stage renal disease, and it is fully justified to call it “a medical catastrophe of worldwide dimension”. Currently, 49% of incident patients in Heidelberg admitted for renal replacement therapy suffer from diabetes mellitus, 6% of type 1 and 94% of type 2. Because the major epidemiologic problem is type 2 diabetes, this text emphasises this type of diabetes.

The presence of diabetes is not only associated with enormous human suffering, but also with an abysmal life expectancy. In a prospective study in Germany, we found that five-year survival was less than 10% in the elderly type 2 diabetics, and no more than 40% in the younger type 1 diabetic patients. The high proportion of type 2 diabetes is grotesque in view of the fact that two decades ago it had been postulated that type 2 diabetes was a benign condition with respect to renal function. This view reflected mainly a bio statistical artifact, since at that time the life expectancy of elderly type 2 diabetics was rather poor.

When one calculates the cumulative prevalence of proteinuria or of renal failure in type 2 diabetics as a function of the years survived, however, the renal risk is either identical or even higher in type 1 compared to type 2 diabetes. The renal complications of diabetes have become one of the greatest challenges of nephrology of today. There is no doubt that in all Western societies the frequency of type 2 diabetes increases dramatically, particularly so in the developing world. Thus, ever more individuals are exposed to the risk of ultimately developing diabetic nephropathy. It is therefore appropriate to briefly discuss the factors underlying this modern “epidemic” of diabetes.

Some Recent Concepts Concerning Type 2 Diabetes

It has been argued that the genetic predisposition to diabetes that is so frequent in Western societies, and even more so in minorities, reflects the fact that in the distant past insulin resistance conferred a survival advantage (“thrifty genotype” hypothesis). This concept finds support in archeologic findings and in the following recent observation. In the aboriginals of Australia, diabetes and diabetic nephropathy develop with excessive frequency. When diabetic aboriginals returned to the lifestyle of their ancestors as hunters and ...