Ahmed Elawwa

Diabetic kidney disease is a major long-term complication of diabetes, with renal injury potentially beginning during childhood or adolescence. This narrative review compares the prevalence, onset, and progression of early renal abnormalities in youth-onset type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM), and summarizes underlying mechanisms and renoprotective strategies. Thirty-nine PubMed-indexed publications met the inclusion criteria. Compared with T1DM, youth-onset T2DM was associated with earlier and more frequent albuminuria, approximately threefold higher hypertension prevalence by early adulthood, earlier hyperfiltration, and nearly twice the cumulative burden of overt diabetic kidney disease by the third decade of life. In T1DM, renal injury is driven mainly by hyperglycemia-related hemodynamic and tubuloglomerular disturbances, whereas in T2DM it is amplified by insulin resistance, visceral adiposity, dyslipidemia, hyperuricemia, and inflammation. Renoprotective strategies include intensive glycemic control, renin-angiotensin system blockade, sodium-glucose cotransporter 2 inhibitors, glucagon-like peptide-1 receptor agonists, and metabolic interventions. Early surveillance for albuminuria, hypertension, and hyperfiltration is warranted in both groups, with particular urgency in youth-onset T2DM.

Youth-onset type 2 diabetes mellitus (T2DM) is a rapidly growing pediatric metabolic disorder that parallels the global childhood obesity epidemic. Despite multiple population-based registries and a global meta-analysis documenting near-universal obesity at the time of a T2DM diagnosis, no integrated synthesis spanning 25 years and including diverse populations has been performed. Here we conducted a systematic review of PubMed and Scopus (January 2000 to March 2025) using longitudinal data from population-based registries in the USA (SEARCH), Canada (Manitoba), England and Wales (National Paediatric Diabetes Audit), Israel, Australia, and New Zealand as well as cross-sectional burden from a global meta-analysis (53 studies, n=8,942) and national audits. Study quality was appraised using the Newcastle-Ottawa Scale and A Measurement Tool to Assess Systematic Reviews v2. All registries showed a temporally parallel increase in the incidence of pediatric obesity and youth-onset T2DM. In the USA, the T2DM incidence rose 79% (3.8 → 6.8 per 100,000/yr, 2002–2018); in Manitoba, it nearly doubled (16.0 → 31.1 per 100,000/yr, 2009–2018); and Israel showed a 441% rise (0.63 → 3.41 per 100,000/yr, 2008–2019). The global pooled obesity prevalence at the T2DM diagnosis was 75.3% (95% confidence interval, 72.1%–78.5%), with approximately 41,600 new youth cases annually worldwide. Once-weekly semaglutide 2.4 mg (STEP TEENS trial) reduced the average body mass index by 16.1% at 68 weeks with concurrent glycemic improvement, while bariatric surgery achieved 95% T2DM remission at 3 years in adolescents (Teen-LABS cohort). Multicontinental evidence confirmed a robust temporally consistent obesity–T2DM link; obesity precedes T2DM at the population level and is present in approximately 75% of affected youths at diagnosis worldwide. Weight-reduction interventions, particularly glucagon-like peptide-1 receptor agonists and bariatric surgery, offer meaningful glycemic benefits; however, primary prevention of childhood obesity remains the most powerful strategy to arrest this epidemic.

Background: Type 2 diabetes mellitus (T2DM) in children and adolescents represents a rapidly escalating global public-health crisis. Evidence drawn from multiple continents indicates that the disease follows an accelerated, more aggressive course in youth than in adults, with multi-organ complications appearing far earlier than historically anticipated. Objectives: [1] To characterize the prevalence and cumulative incidence of each major complication domain in youth-onset T2DM using data from international cohorts; [2] to compare complication burden across geographic regions and ethnic populations; and [3] to identify modifiable risk factors to guide evidence-based clinical management. Methods: PubMed/MEDLINE, EMBASE, and the Cochrane Library were searched systematically from January 1995 to December 2023. Eligible studies enrolled participants aged ≤18 years with T2DM and reported at least one complication outcome. Thirty-eight studies (N = 42,610 participants across North America, Europe, Asia-Pacific, the Middle East, and Australia) met inclusion criteria. Quality was assessed using the Newcastle-Ottawa Scale (NOS) and the Cochrane RoB-2 tool; pooled estimates were generated using random-effects meta-analysis. Results: Across all regions, hypertension was the most frequent complication (pooled prevalence 42–68%), followed by diabetic kidney disease (DKD; 22–55%), dyslipidemia (38–52%), retinopathy (13–51%), and peripheral neuropathy (12–32%). MASLD/NAFLD affects 40–70% of patients globally. Data from the USA (TODAY, SEARCH), Asia-Pacific (JADE program), Europe (UK and Italian cohorts), multi-national meta-analyses (Nanayakkara et al., 26 countries), and Australia were convergent in demonstrating that each additional year of younger age at diagnosis conferred a 4–5% incremental increase in vascular complication risk. Mental health disorders affected 15–32% of youth with T2DM across all populations studied. Youth-onset T2DM consistently showed higher complication rates than both adult-onset T2DM of equivalent duration and youth-onset T1DM. Conclusions: Youth-onset T2DM imposes an internationally consistent, uniquely aggressive complication phenotype that transcends ethnic and geographic boundaries. Complications worldwide must implement complication screening from the time of diagnosis, integrate psychosocial support, and adopt newer pharmacotherapies with organ-protective properties. Investment in equitable, globally applicable, pediatric-specific protocols is urgently needed