Related Experiment Video
Updated: Aug 8, 2026
An Assay to Detect Protection of the Retinal Vasculature from Diabetes-Related Death in Mice
Published on: January 12, 2024
Relationship between blood glucose control, pathogenesis and progression of diabetic nephropathy
Romano Nosadini1, Giancarlo Tonolo
1Department of Endocrinology and Metabolic Diseases, University of Sassari, Clinica Medica, Sassari, Italy. noscia@tin.it
Abstract:
The present review briefly discusses evidence that the risk of a rapid decline of glomerular function abruptly increases when glycated hemoglobin is steadily higher than 7.5% and postprandial blood glucose is >200 mg/dl. The capacity to accomplish and to maintain steadily tightly controlled blood glucose levels is scanty using the currently implemented hypoglycemic drugs. Moreover, it must be highlighted that most patients with type 2 diabetes, particularly when renal damage does occur, have arterial hypertension. Several studies suggested that the development of ESRD is prevented significantly better by drugs that modulate the renin angiotensin system than by other compounds in patients with type 1 and 2 diabetes with overt diabetic nephropathy. However, a recent trial, the study Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), which compared lisinopril, chlorthalidone, and amlodipine in a large population of patients with arterial hypertension, either associated or not with diabetes, demonstrated that the development of both coronary heart diseases and renal complications was equally prevented by the three drugs. One word of caveat, however, needs to be raised concerning one of the results of the ALLHAT study: the higher risk of developing new-onset diabetes among hypertensive patients who are not treated with lisinopril. Even if it is true that this latter side effect was not accompanied by a worse outcome of macrovascular and renal complications during the 5-yr follow-up period, one cannot rule out the possibility that this might be the case during more prolonged periods of follow-up in the future. Thus, the advantage of a lower cost in the treatment of hypertension with diuretics as compared with other drugs, with similar degree of success in the prevention of vascular complications, should be weighed also taking into consideration the burden of a higher rate of occurrence of new-onset diabetes.
Insights
Maintaining blood glucose below 7.5% glycated hemoglobin and 200 mg/dl postprandial glucose is crucial for kidney function in diabetics. While renin-angiotensin system drugs show promise, the ALLHAT trial suggests comparable renal protection from other antihypertensives, with a note on new-onset diabetes risk.
Area of Science:
- Nephrology
- Endocrinology
- Cardiology
Background:
- Elevated glycated hemoglobin (>7.5%) and postprandial glucose (>200 mg/dl) significantly increase the risk of rapid glomerular function decline.
- Current hypoglycemic drugs often show limited efficacy in achieving and maintaining tight glycemic control in type 2 diabetes.
- Arterial hypertension is a common comorbidity in type 2 diabetes patients, especially those with existing renal damage.
Purpose of the Study:
- To review evidence on glycemic control targets for preventing diabetic kidney disease progression.
- To evaluate the role of renin-angiotensin system (RAS) inhibitors versus other antihypertensives in preventing end-stage renal disease (ESRD).
- To analyze findings from the ALLHAT trial regarding cardiovascular and renal outcomes across different antihypertensive classes, including the incidence of new-onset diabetes.
Main Methods:
- Review of existing literature and clinical trial data concerning diabetes management, nephropathy, and hypertension.
- Analysis of evidence supporting the efficacy of RAS inhibitors in diabetic nephropathy.
- Examination of the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) results comparing lisinopril, chlorthalidone, and amlodipine.
Main Results:
- Studies suggest RAS modulators offer superior protection against ESRD in diabetic nephropathy compared to other agents.
- The ALLHAT trial indicated comparable prevention of coronary heart disease and renal complications among lisinopril, chlorthalidone, and amlodipine.
- A significant finding from ALLHAT was an increased risk of new-onset diabetes in hypertensive patients not treated with lisinopril.
Conclusions:
- Achieving strict glycemic control is paramount for preserving glomerular function in diabetic patients.
- While RAS inhibitors show specific benefits in diabetic nephropathy, other antihypertensives like diuretics may offer similar broad cardiovascular and renal protection.
- The potential for increased new-onset diabetes with non-lisinopril antihypertensives necessitates careful consideration of long-term risks versus cost-effectiveness in hypertension management.
Related Concept Videos
01:25Chronic Kidney Disease I: Introduction
01:24Type II Diabetes II: Pathophysiology
01:29Hyperglycemia
01:27Diabetic Retinopathy
01:28Diabetic Nephropathy
01:22Diabetic Neuropathy