High risk of ESRD in type 1 diabetes: new strategies are needed to retard progressive renal function decline.

Care of patients with type 1 diabetes (T1D) has changed during the past 30 years. Tools to control hyperglycemia have improved and it was shown that improvement in glycemic control diminished the risk of late diabetic complications, including nephropathy. Moreover, in patients with impaired renal function, aggressive treatment of hypertension and renoprotective blockade of the renin-angiotensin system were shown to postpone end-stage renal disease (ESRD), albeit for a short while.

Sustained endotoxemia leads to marked down-regulation of early steps in the insulin-signaling cascade.

Objectives: To determine the effects of sustained, 3-day endotoxin infusion on early steps of the insulin-signaling pathway in rat liver and skeletal muscle in vivo; to examine insulin signaling in well-established acute endotoxin models of insulin resistance.

Design: Prospective, controlled animal study.

Setting: University research laboratory.

Angiotensin-converting enzyme inhibition suppresses plasminogen activator inhibitor-1 expression in the neointima of balloon-injured rat aorta.

Background: Plasminogen activator inhibitor-1 (PAI-1), an important regulator of fibrinolysis and extracellular matrix turnover, has been implicated in a number of vascular diseases. Studies demonstrating angiotensin II (Ang II) to be a potent stimulator of PAI-1 expression in cultured vascular cells suggests that the renin-angiotensin system may modulate vascular PAI-1 expression.

Methods And Results: We examined the effects of the ACE inhibitor captopril on PAI-1 expression in control and balloon-injured rat aorta.

Predisposition to hypertension and susceptibility to renal disease in insulin-dependent diabetes mellitus.

Only one third of patients with juvenile-onset insulin-dependent diabetes seem to be susceptible to diabetic nephropathy. To test whether this susceptibility is related to a predisposition to hypertension, we investigated the association of nephropathy with markers of risk for hypertension. We randomly selected 89 patients with insulin-dependent diabetes from a roster of children and adolescents who were seen between 1968 and 1972 at about the time the diagnosis was made.