Key result
ACE D allele linked to ~5-fold higher risk of albuminuria and reduced eGFR in pediatric T1D.
Why the study?
Diabetic nephropathy often develops silently in type 1 diabetic children, and the role of ACE gene polymorphism as an early predictor was unclear.
Does the ACE gene D allele or DD genotype predict early diabetic nephropathy in pediatric patients with type 1 diabetes mellitus?
Cross-Sectional (n=48)
No
Does the ACE gene D allele or DD genotype predict early diabetic nephropathy in pediatric patients with type 1 diabetes mellitus?
Odds Ratio: 5.28 (95% CI 1.46–19.14)
p-value: p=<0.001
The ACE gene D allele and DD genotype are significantly associated with early diabetic nephropathy in pediatric type 1 diabetes, suggesting its utility as a non-invasive predictive biomarker for early risk stratification.
ACE I/D polymorphism was associated with DN risk in type 1 diabetic children; hypothesis-generating and requires prospective validation before clinical use.
Background Diabetic nephropathy (DN) is a severe complication among type 1 diabetic children, often developing silently before clinical detection. Genetic polymorphisms particularly the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene may influence susceptibility and offer a potential tool for earlier identification. This research aimed to evaluate the role of ACE gene polymorphism as an early predictor of DN among type 1 diabetic children. Methods We included 48 children with type 1 diabetes mellitus in this cross-sectional study. Patients were classified into three groups: without nephropathy (58.3%), with albuminuria and preserved eGFR (27.1%), and with albuminuria and reduced eGFR (14.6%). Clinical evaluation and laboratory investigations including HbA1c, albumin-to-creatinine ratio (ACR), microalbuminuria, serum creatinine, lipid profile, and eGFR were performed. The ACE gene polymorphism was assessed by PCR amplification using allele-specific primers. Results Age showed a significant variation across studied groups ( P = 0.001), with higher values observed among patients with advanced nephropathy. Glycemic control was poorer in affected groups, as indicated by elevated HbA1c levels ( P < 0.001). Renal involvement was evident by increased ACR, microalbuminuria, and serum creatinine, along with a significant decline in eGFR ( P < 0.001). A significant variation in ACE genotype distribution was detected ( P = 0.004), with the DD genotype being more prevalent among patients with DN. Specifically, the D allele was significantly associated with a higher risk of albuminuria (OR = 2.88) and combined renal impairment (OR = 5.28) ( P < 0.001). Furthermore, the DD genotype was linked to worse glycemic and renal parameters ( P < 0.05). Conclusion The ACE gene D allele and DD genotype are significantly associated with early diabetic nephropathy in children with type 1 diabetes mellitus, correlating with reduced eGFR and elevated albuminuria. ACE genotyping can serve as a valuable non-invasive predictive biomarker to identify high-risk pediatric patients for early nephroprotective interventions.
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Gehad et al. (2026) conducted a cross-sectional in Type 1 diabetes mellitus and diabetic nephropathy (n=48). ACE gene D allele and DD genotype vs. ACE gene I allele and II/DI genotypes was evaluated on Combined albuminuria and reduced eGFR (Group III vs Group I for D allele) (OR 5.28, 95% CI 1.46-19.14, p=<0.001). The ACE gene D allele was significantly associated with a 5.28-fold increased risk of combined albuminuria and reduced eGFR in children with type 1 diabetes.
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