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Predisposition to hypertension: risk factor for nephropathy and hypertension in IDDM
J Barzilay1, J H Warram, M Bak
1Epidemiology and Genetics Section, Brigham and Women's Hospital, Boston Massachusetts.
Insights
Genetic predisposition to hypertension and higher red blood cell Na/Li countertransport Vmax are key risk factors for developing diabetic nephropathy in juvenile-onset type 1 diabetes. Poor glycemic control also contributes to advanced nephropathy.
Area of Science:
- Endocrinology
- Nephrology
- Genetics
Background:
- Diabetic nephropathy is a common complication of type 1 diabetes.
- Identifying early risk factors is crucial for prevention and management.
Purpose of the Study:
- To investigate the determinants of diabetic nephropathy in patients with juvenile-onset type 1 diabetes.
- To compare risk factors among patients with advanced nephropathy, microalbuminuria, and hypertension alone versus controls.
Main Methods:
- Case-control study design.
- Inclusion of patients diagnosed with juvenile-onset type 1 diabetes between 1967-1972, examined 15-21 years later.
- Comparison of groups: advanced nephropathy, microalbuminuria, hypertension alone, and normoalbuminuric/normotensive controls.
Main Results:
- Advanced nephropathy linked to parental hypertension (OR 3.8), high red blood cell Na/Li countertransport Vmax (OR 10.0), and higher adolescent/early adult mean arterial pressure (OR 3.1).
- Poorer glycemic control in the first 12 years was associated with advanced nephropathy.
- Hypertension alone group showed strong hypertension predisposition markers but better glycemic control than nephropathy group.
Conclusions:
- Predisposition to hypertension is a significant risk factor for advanced diabetic nephropathy and essential hypertension in type 1 diabetes.
- Red blood cell Na/Li countertransport Vmax and early-life blood pressure are important predictors.
- Microalbuminuria alone did not show a significant predisposition to hypertension.
Abstract:
Less than a quarter of the patients with juvenile-onset IDDM develop diabetic nephropathy during the first 20 years of diabetes. To study the determinants of this complication, we selected patients who had come with newly diagnosed IDDM to the Joslin Clinic between 1967 to 1972, and we examined them in 1986 to 1988, that is, 15 to 21 years after onset of diabetes. Using a case control design we compared three groups of cases, that is, advanced nephropathy (N = 43), only microalbuminuria (N = 41), and hypertension alone (N = 17), with a group of controls who remained normoalbuminuric and normotensive despite the long duration of IDDM (N = 61). In comparison with controls, patients with advanced nephropathy had more parents with hypertension (odds ratio 3.8), higher Vmax values of Na/Li countertransport in red blood cells (odds ratio 10.0 for the highest tertile), and higher mean arterial pressure during adolescence and early adulthood (odds ratio 3.1 for those above the median). They also had significantly poorer glycemic control during their first 12 years of diabetes. Patients with hypertension alone were similar to those with advanced nephropathy with regard to markers of predisposition to hypertension but differed from them with regard to glycemic control, having the best glycemic control of all the study groups. Patients who developed only microalbuminuria during 15 to 21 years of IDDM (some of whom will progress to overt proteinuria later) did not differ significantly from controls with regard to predisposition to hypertension. In conclusion, predisposition to hypertension is a major risk factor for the development of advanced diabetic nephropathy and essential hypertension during the first 20 years of IDDM.