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Editorial Diabetes An Advancing Avalanche—The Emergence of Complications in Indigenous Youth with Type 2 Diabetes Elizabeth AC Sellers Department of Pediatrics and Child Health, Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada; Children’s Hospital Research Institute of Manitoba, Winnipeg, Manitoba, Canada Abstract Youth-onset type 2 diabetes (diagnosed <18 years of age) is increasing around the world. Indigenous populations are disproportionally affected. The classic microvascular complications of diabetes are now emerging in this population and early data suggest that complications may occur early and more aggressively in youth-onset versus adult-onset disease. Of concern are the transgenerational effects of youth-onset diabetes, with increasing rates of pregestational exposure to diabetes, a potent risk factor for the development of youth-onset type 2 diabetes. Keywords Type 2 diabetes, youth, adolescent, Indigenous, complications Disclosure: Elizabeth AC Sellers has nothing to disclose in relation to this article. This article is a short opinion piece and has not been submitted to external peer reviewers. No funding was received in the publication of this article. Open Access: This article is published under the Creative Commons Attribution Noncommercial License, which permits any noncommercial use, distribution, adaptation, and reproduction provided the original author(s) and source are given appropriate credit. Received: March 21, 2016 Published Online: April 15, 2016 Citation: US Endocrinology 2016;12(1):16–7 Correspondence: Elizabeth AC Sellers, University of Manitoba, FE-307 685 William Avenue, Winnipeg, MB, Canada, R3E 0Z2. E: An avalanche is “a sudden arrival or occurrence of something in overwhelming quantities”. 1 Is this an accurate description of the emerging complications seen in those with youth-onset type 2 diabetes? Type 2 diabetes of youth onset (diagnosed <18 years of age) is increasing around the world. 2 However, incident rates vary markedly between populations with Indigenous populations bearing a particularly high burden. In Canada, Indigenous youth represent approximately 45% of youth-onset type 2 diabetes, despite comprising less than 10 % of the Canadian childhood population. 3 Similarly, Native American youth have an incidence rate three to four times higher than non-Hispanic white youth in the US. 4 The youngest reported case of type 2 diabetes is in an Indigenous child from the Torres Strait, who was diagnosed at the age of five. 5 Early data suggest that complications may occur early and more aggressively in youth-onset versus adult-onset disease. 6 Data on both the acute and chronic complications of type 2 diabetes of youth-onset are just now emerging and, given the increased burden in indigenous children, much of the data available are for the Indigenous population. The morbidity of these children is high, and the majority of youth with type 2 diabetes have, at a minimum, two major health concerns—diabetes and obesity. Many have additional comorbidities such as dyslipidemia, hypertension, and fatty liver disease. 3 The classic long-term microvascular complications of diabetes have now been described in young adults with youth-onset type 2 diabetes. Renal health is a particular concern in Indigenous youth as this population is 16 also at increased risk for primary non-diabetic renal disease. 7–9 Thus, indigenous youth with type 2 diabetes may have both diabetes and an underlying primary renal disease, placing them at significant risk for poor renal outcomes. Micro- and macroalbuminuria are frequently present at diagnosis of youth-onset type 2 diabetes. For example, albuminuria was present at diagnosis in 22% of Pima Indian youth, 29% of Canadian First Nation (FN) youth and in 14% of New Zealand Maori youth. 7,10,11 Progression also appears to be rapid, with albuminuria described in 58% of Pima youth and 62% of Maori youth within 10 years of diagnosis. 10,11 In a recent Canadian study, persistent, non-orthostatic albuminuria was present in 9.8% of FN children compared with 1.8% of non-FN children with type 2 diabetes. 12 FN children from Manitoba with type 2 diabetes had a four-fold increased risk of renal failure compared with youth with type 1 diabetes controlled for age at diagnosis, glycated hemoglobin (HbA1c), era of diagnosis, and body mass index z-score, and a 23-fold increased risk of renal failure compared to age-, sex, and geographically matched control children without diabetes. 13 Other microvascular complications are also reported at high rates among those with youth-onset type 2 diabetes. Increased rates of neurological complications in those with type 2, compared with type 1 diabetes begin to appear by five years post-diagnosis and ophthalmologic complications begin to differ 10 years post-diagnosis. Major complications (defined as amputation, blindness, or dialysis) remained rare in youth-onset type 1 diabetes 20 years post-diagnosis, but occurred in 26% of youth-onset type 2 diabetes 10 years post- diagnosis and in almost 50% 20 years post-diagnosis. 14 TOUCH ME D ICA L ME D IA