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Risk of early-onset proliferative retinopathy in IDDM is closely related to cardiovascular autonomic neuropathy
A S Krolewski1, J Barzilay, J H Warram
1Epidemiology and Genetics Section, Joslin Diabetes Center, Boston, Massachusetts 02215.
Insights
Poor glycemic control and cardiovascular autonomic neuropathy significantly increase the risk of early-onset proliferative diabetic retinopathy (PDR) in patients with insulin-dependent diabetes mellitus (IDDM). Impaired renal function also presents an extremely high risk for PDR development.
Area of Science:
- Ophthalmology
- Endocrinology
- Nephrology
Background:
- Proliferative diabetic retinopathy (PDR) is a major complication of insulin-dependent diabetes mellitus (IDDM).
- Early-onset PDR developing within the second decade of IDDM requires investigation into its specific determinants.
Purpose of the Study:
- To investigate the risk factors associated with early-onset PDR in patients with juvenile-onset IDDM.
- To identify key determinants contributing to the development of PDR during the second decade of diabetes.
Main Methods:
- A nested case-control study was conducted using an inception cohort of patients with juvenile-onset IDDM.
- Cases (n=74) with PDR were compared to control subjects (n=88) without PDR.
- Risk factors analyzed included glycemic control, cardiovascular autonomic neuropathy (CAN), and nephropathy (albuminuria, renal function).
Main Results:
- Poor glycemic control over the first 12 years of diabetes was strongly associated with increased PDR risk (4-5 fold higher in higher hyperglycemia quartiles).
- Cardiovascular autonomic neuropathy (CAN) showed a striking association with PDR (ORs of 77.5 for significant CAN, 34.6 for mild CAN).
- Nephropathy, particularly impaired renal function, presented an extremely high risk for PDR (infinite OR), while microalbuminuria and proteinuria showed moderate increases in risk.
Conclusions:
- Poor glycemic control is a primary determinant of early-onset PDR in IDDM.
- Cardiovascular autonomic neuropathy and nephropathy are significant risk factors for PDR.
- While nephropathy markers are associated with PDR, glycemic control appears to be the most critical factor.
Abstract:
Determinants of proliferative diabetic retinopathy (PDR) that occur during the 2nd decade of insulin-dependent diabetes mellitus (IDDM) (early-onset PDR) were investigated in a nested case-control study. From an inception cohort of patients with juvenile-onset IDDM that now has 15-21 yr diabetes duration, the patients with PDR (cases, n = 74) were selected for study along with a random sample of the patients in the cohort without PDR (control subjects, n = 88). The risk of PDR was associated with poor glycemic control during the first 12 yr of diabetes. Relative to patients in the first quartile of the index of hyperglycemia, those in higher quartiles and nonattenders had a four- to fivefold risk of developing PDR. A striking relationship with cardiovascular autonomic neuropathy (CAN) was found. Relative to patients without CAN, patients with significant and mild CAN had odds ratios of 77.5 and 34.6, respectively. Patients with albumin excretion rates greater than 30 micrograms/min had moderately increased risk of PDR (ranging from 4-fold for microalbuminuria to 7-fold for proteinuria). In contrast, patients with impaired renal function had an extremely high risk of PDR. All 20 of these patients were cases, therefore the odds ratio was infinite. All three factors (poor glycemic control, CAN, and various stages of nephropathy) were associated with PDR in multiple logistic regression analysis. However, in models including glycemic control, the association between microalbuminuria or proteinuria and PDR was weakened. In conclusion, our findings are consistent with a hypothesis that the level of glycemia is a primary determinant of early-onset PDR.(ABSTRACT TRUNCATED AT 250 WORDS)