Study design and results from the DCCT

What clinical trial endpoints have been shown to improve when ACE inhibitors and/or ARBS are  used in preventing the progression of kidney disease in patients with diabetes?  Which patients with diabetes benefit the most?  At what point is it recommended that an ACE inhibitor or ARB be initiated in a patient with diabetes?

Formulate a response to this discussion.

In the study Role of ACE inhibitors in Patients with Diabetes Mellitus the results showed that that not only do ACE inhibitors help to slow the progression of kidney disease but that they also help with the protection of other organs. “ACE inhibitors have been reported to improve kidney, heart, and to a lesser extent, eye and peripheral nerve function of patients with diabetes mellitus.” This study was more directed at providing evidence of adding the ACE inhibitor earlier in therapy because it could help prevent other complications in the future such as kidney disease. ACE inhibitors are already indicated in patients with hypertension. I can understand their thought process in doing this but only in high risk diabetes patients for high blood pressure, mainly type 2 diabetes. The patients that benefit the most from taking an ACE or an ARB for preventing the progression of kidney disease is someone who has hypertension or proteinuria. I would also argue that someone who could benefit the most is someone who is high risk for hypertension. Overall there is a lot of evidence from lots of studies pointing towards ACE inhibitors and ARBs being given in patients with both diabetes and hypertension, and this is why it’s initiated after patients have both.

Formaulate response to this discussion.

There is a renoprotective effect that ARBs and ACE inhibitors possess that makes them a good candidate to help prevent kidney issues within patients with diabetes. There is evidence for ACE inhibitors in type 1 and ARBs for type 2 diabetes to reduce progression in both diseases. For ACE inhibitors this is seen because of moderately increased albuminuria, there was a study where a diabetic patient had decreased albumin excretion and after two years of disease progression the patients on ACE inhibitors had less albuminuria than those with placebo. There was another study that had overt nephropathy and randomly assigned therapies with either captopril or a placebo. After 4 years patients with captopril had slower rate of creatine increases with less likelihood of progressing to end stage renal disease. This however only worked for patients with creatine of greater than 1.5 mg/dL and it was reduced by 50% per year compared to placebo group. There was no improvement for those with lower baseline plasma creatinine concentration because the rate of progression is slow. Some patients had antiproteinuric effects with remission or regression of nephropathy, 40 were randomly assigned to active therapy with captopril and after 7.7 years 6 patients were still in remission with lower proteinuria after using an ACE inhibitor of captopril. Aggressive blood pressure therapy has been connected with remission and regression. After treatment with ACE inhibitors the rate of decline in GFR was faster after a nine year follow up.

A good reason this method is effective has to do with good blood pressure control and management is a key factor in preventing progression of diabetic nephropathy. United Kingdom Prospective Diabetes Study determined that 10 mmHG reduction in systolic pressure gives a 12% decrease in risk for diabetic complications. This would indicate that by utilizing these avenues of ACE inhibitor or ARBs to control blood pressure would indirectly reduce a patient’s risk of developing kidney disease complications.

Both diabetic types receive effects from this type of treatment, however it was found that ARBs have better efficacies and that could be a better form for treatment in both type 1 and type 2. With that said, ACE inhibitors have been frequently tested in type 1 diabetics whereas ARBs were tested in type 2. Both had seemingly congruent results that lead to believe either treatment would be recommended but distinguished in which type of diabetes a patient is suffering from.

Patients with urinary albumin excretion rates of 30 to 300 mg in 24 hours are those who should be prescribed these medications in order to utilize this special property for stalling of diabetic nephropathy disease in both type 1 and type 2 diabetic patients which was recommended by the The Kidney Disease: Improving Global Outcomes guidelines . After doing a lot of research on this topic my results found that the best method for this prevention of diabetic kidney disease is by using both an ACE inhibitor and ARB together to have a greater reduction in protein excretion, but it was concluded to not use these medications at the same time as it increases likelihood of adverse events.. There however is more data for ARB efficacy rather than ACE inhibitors with this indication.

1. Discuss the study design and results from the DCCT (Diabetes Control and Complications Trial) relating to the impact of glucose control on the progression of diabetic kidney disease. (The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. The Diabetes Control and Complications Trial Research Group. N Engl J Med 1993;329:977-986.)

2. What clinical trial endpoints have been shown to improve when ACE inhibitors and/or ARBS are used in preventing the progression of kidney disease in patients with diabetes? Which patients with diabetes benefit the most? At what point is it recommended that an ACE inhibitor or ARB be initiated in a patient with diabetes?

3. Discuss the results of the ONTARGET trial (Renal outcomes with telmisartan, ramipril or both in people at high vascular risk: a multicentre, randomized, double-blind, controlled trial. Lancet 2008;372:547-53.) with regard to renal outcomes seen when an ACE inhibitor was combined with an ARB for renal protection. What do the ADA and JNC 8 recommend in regard to the combination?