Diabetic nephropathy-an evaluation of potential risk factors in young patients with type 1 diabetes mellitus

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Abstract

BACKGROUND

Microalbuminuria represents a marker of incipient diabetic nephropathy, whereas macro albuminuria is associated with overt diabetic nephropathy, a condition that can progress to end stage renal disease (ESRD).

OBJECTIVE

To determine the relationship between albuminuria and risk factors for nephropathy in patients with type 1 diabetes mellitus (T1DM).

DESIGN AND INTERVENTION

The German Diabetes Documentation System was a multicenter, prospective cohort study of pediatric and adult patients with T1DM who were registered at specialized diabetes care centers in Austria and Germany. Inclusion criteria included at least two documented urine tests for albuminuria. Urine albumin excretion rate (AER), albumin to creatinine ratio (ACR), and overnight albumin concentration were used to screen for albuminuria. Diagnostic cut off values for microalbuminuria were an AER ≥20 μg/min and an ACR ≥2.5 mg/mmol. Macroalbuminuria was defined as an AER ≥200 μg/min and an ACR ≥35 mg/mmol. Dyslipidemia was defined as the presence of at least one elevated lipid parameter (total cholesterol, LDL cholesterol or triglycerides). Hypertension was defined as the median value >95th percentile of at least three independent blood pressure measurements. Other factors assessed included glycemic control, smoking history, use of antihypertensive or lipid lowering drugs, duration of T1DM, and age at diagnosis.

OUTCOME MEASURES

The main outcome measures were albuminuria, HbA1c level, lipid profile, and blood pressure.

RESULTS

The study evaluated 27,805 children, adolescents and adults with T1DM. Cohort characteristics included mean age at diagnosis 12.9 years, disease duration 8.3 years, age at last study visit 21.1 years, HbA1c level 7.99%, and male sex 52.5%. The median follow-up time was 2.5 years. A total of 26,605 patients had normal urine tests; by contrast, 919 patients had microalbuminuria, 52 had macroalbuminuria and 229 had ESRD. Kaplan Meier analysis demonstrated that 25.4% of patients had microalbuminuria and 9.4% had macroalbuminuria or ESRD after a median disease duration of 40 years. Patients with an HbA1c level >7.5% developed microalbuminuria and macroalbuminuria earlier than those patients with an HbA1c level >7.5% (P >0.005 for both comparisons). Differences between these two patient groups were apparent after 10 years' disease duration for micro albuminuria and after 20 years' disease duration for macroalbuminuria. Risk factors for micro albuminuria included disease duration (odds ratio [OR] 1.033), age at diagnosis (OR 1.011), HbA1c level (OR 1.130), LDL cholesterol level (OR 1.003), triglyceride level (OR 1.003), systolic blood pressure (OR 1.008), and diastolic blood pressure (OR 1.014). Male sex was a risk factor for macroalbuminuria (OR 1.290), as was disease duration, HbA1c level, dyslipidemia, and hypertension.

CONCLUSION

Poor glycemic control, dyslipidemia, hypertension, disease duration, and male sex were all identified as independent risk factors for diabetic nephropathy in patients with T1DM.

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