The Journal of Pediatrics
Volume 153, Issue 3 , Pages 442-443, September 2008

Poor glycemic control predicts occurrence and progression of microalbuminuria in children with type I diabetes

University of Wisconsin American Family Children's Hospital, Madison, Wisconsin

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Amin R, Widmer B, Prevost AT, Schwarze P, Cooper J, Edge J, et al. Risk of microalbuminuria and progression to macroalbuminuria in a cohort with childhood onset type 1 diabetes: prospective observational study. BMJ 2008;336:697-701 

Question Among children with childhood-onset type 1 diabetes, what factors predict microalbuminuria and progression to macroalbuminuria?

Design Prospective observational study with follow-up for 9.8 (SD 3.8) years.

Setting Oxford regional prospective study.

Participants A total of 527 children (mean age 8.8 years) with a diagnosis of type 1 diabetes.

Outcomes Annual measurement of glycosylated hemoglobin (HbA1c) and assessment of urinary albumin/creatinine ratio.

Main Results Cumulative prevalence of microalbuminuria was 25.7% (95% confidence interval 21.3% to 30.1%) after 10 years of diabetes and 50.7% (40.5% to 60.9%) after 19 years of diabetes and 5182 patient years of follow-up. The only modifiable adjusted predictor for microalbuminuria was high HbA1c concentrations (hazard ratio per 1% rise in HbA1c 1.39, 1.27 to 1.52). Blood pressure and history of smoking were not predictors. Microalbuminuria was persistent in 48% of patients. Cumulative prevalence of progression from microalbuminuria to macroalbuminuria was 13.9% (12.9% to 14.9%); progression occurred at a mean age of 18.5 (5.8) years. Although the sample size was small, modifiable predictors of macroalbuminuria were higher HbA1c levels and both persistent and intermittent microalbuminuria (hazard ratios 1.42 [1.22 to 1.78], 27.72 [7.99 to 96.12], and 8.76 [2.44 to 31.44], respectively).

Conclusions In childhood-onset type 1 diabetes, the only modifiable predictors were poor glycemic control for the development of microalbuminuria and poor control and microalbuminuria (both persistent and intermittent) for progression to macroalbuminuria. Risk for macroalbuminuria is similar to that observed in cohorts with adult-onset disease, but as it occurs in young adult life, early intervention in adolescents with normal blood pressure might be needed to improve prognosis.

Commentary Diabetic nephropathy is common, presaged by microalbuminuria, and is largely preventable.1 Amin et al use a large cohort and lengthy follow-up to describe, as previously done in adults,2, 3 independent predictors for progression from microalbuminuria to macroalbuminuria in children with type 1 diabetes. They conclude that poorer glycemic control is the only modifiable predictor of occurrence and worsening of albuminuria. The accuracy and clinical value of this assertion could be affected by several aspects of the study. First, the authors have analyzed all patients with transient, intermittent, and persistent microalbuminuria together, whereas it is known that each is a distinct entity with different consequences. Second, the absence of body mass index analysis may be a critical omission, because obesity is a known contributor to microalbuminuria in nondiabetic adolescents and must be considered.4 Third, the description of high blood pressure as a significant but non-modifiable predictor of occurrence and progression of microalbuminuria is confusing and potentially misleading. Angiotensin-converting enzyme inhibitor treatment of patients with type 1 diabetes with microalbuminuria can prevent or delay the progression to overt diabetic nephropathy.5 In this study, only 15% of patients with microalbuminuria were so treated, limiting adequate assessment of the potential role of blood pressure modification. Finally, the relatively poor glycemic control (mean HbA1c 9.8% ± 1.6%) and lack of information regarding the patients' insulin regimens limit the applicability of these data to contemporary patients. Thus although this study adds to our knowledge of the causes and course of microalbuminuria in children with type 1 diabetes, further well-designed studies with attention to the aforementioned analyses are needed to determine how best to manage blood sugar control, blood pressure, body weight, and other factors to prevent diabetic nephropathy.

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References 

  1. National diabetes fact sheet: general information and national estimates on diabetes in the United States. http://www.cdc.gov/diabetes/pubs/pdf/ndfs2003.pdf2003;
  2. Hovind P, Tamow L, Rossing P, Jensen BR, Graae M, Torp I, et al. Predictors for the development of microalbuminuria and macroalbuminuria in patients with type 1 diabetes: inception cohort study. BMJ. 2004;328:1105
  3. Perkins BA, Ficociello LH, Silva KH, Finkelstein DM, Warram JH, Krolewski AS. Regression of microalbuminuria in type 1 diabetes. N Engl J Med. 2003;348:2285–2293
  4. Burgert TS, Dziura J, Yeckel C, Taksali SE, Weiss R, Tamborlane W, et al. Microalbuminuria in pediatric obesity: prevalence and relation to other cardiovascular risk factors. Int J Obes. 2006;30:273–280
  5. The microalbuminuria captopril study group. Captopril reduces the risk of nephropathy in IDDM patients with microalbuminuria. Diabetologia. 1996;39:587–593

PII: S0022-3476(08)00488-5

doi:10.1016/j.jpeds.2008.05.057

The Journal of Pediatrics
Volume 153, Issue 3 , Pages 442-443, September 2008

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