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Youth-onset type 2 diabetes mellitus: an urgent challenge.

ABSTRACT: The incidence and prevalence of youth-onset type 2 diabetes mellitus (T2DM) and its complications are increasing worldwide. Youth-onset T2DM has been reported in all racial and ethnic groups, but Indigenous peoples and people of colour are disproportionately affected. People with youth-onset T2DM often have a more aggressive clinical course than those with adult-onset T2DM or those with type 1 diabetes mellitus. Moreover, the available treatment options for children and adolescents with T2DM are more limited than for adult patients. Intermediate complications of youth-onset T2DM, such as increased albuminuria, often develop in late childhood or early adulthood, and end-stage complications, including kidney failure, develop in mid-life. The increasing frequency, earlier onset and greater severity of childhood obesity in the past 50 years together with increasingly sedentary lifestyles and an increasing frequency of intrauterine exposure to diabetes are important drivers of the epidemic of youth-onset T2DM. The particularly high risk of the disease in historically disadvantaged populations suggests an important contribution of social and environmental factors, including limited access to high-quality health care, healthy food choices and opportunities for physical activity as well as exposure to stressors including systemic racism and environmental pollutants. Understanding the mechanisms that underlie the development and aggressive clinical course of youth-onset T2DM is key to identifying successful prevention and management strategies.

SUBMITTER: Bjornstad P

PROVIDER: S-EPMC10182876 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature

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Youth-onset type 2 diabetes mellitus: an urgent challenge.

Bjornstad Petter P Chao Lily C LC Cree-Green Melanie M Dart Allison B AB King Malcolm M Looker Helen C HC Magliano Dianna J DJ Nadeau Kristen J KJ Pinhas-Hamiel Orit O Shah Amy S AS van Raalte Daniel H DH Pavkov Meda E ME Nelson Robert G RG

Nature reviews. Nephrology 20221031 3

The incidence and prevalence of youth-onset type 2 diabetes mellitus (T2DM) and its complications are increasing worldwide. Youth-onset T2DM has been reported in all racial and ethnic groups, but Indigenous peoples and people of colour are disproportionately affected. People with youth-onset T2DM often have a more aggressive clinical course than those with adult-onset T2DM or those with type 1 diabetes mellitus. Moreover, the available treatment options for children and adolescents with T2DM are ...[more]

PMID: 36316388

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Project description:BackgroundThe prevalence of type 2 diabetes in youth is increasing, but little is known regarding the occurrence of related complications as these youths transition to adulthood.MethodsWe previously conducted a multicenter clinical trial (from 2004 to 2011) to evaluate the effects of one of three treatments (metformin, metformin plus rosiglitazone, or metformin plus an intensive lifestyle intervention) on the time to loss of glycemic control in participants who had onset of type 2 diabetes in youth. After completion of the trial, participants were transitioned to metformin with or without insulin and were enrolled in an observational follow-up study (performed from 2011 to 2020), which was conducted in two phases; the results of this follow-up study are reported here. Assessments for diabetic kidney disease, hypertension, dyslipidemia, and nerve disease were performed annually, and assessments for retinal disease were performed twice. Complications related to diabetes identified outside the study were confirmed and adjudicated.ResultsAt the end of the second phase of the follow-up study (January 2020), the mean (±SD) age of the 500 participants who were included in the analyses was 26.4±2.8 years, and the mean time since the diagnosis of diabetes was 13.3±1.8 years. The cumulative incidence of hypertension was 67.5%, the incidence of dyslipidemia was 51.6%, the incidence of diabetic kidney disease was 54.8%, and the incidence of nerve disease was 32.4%. The prevalence of retinal disease, including more advanced stages, was 13.7% in the period from 2010 to 2011 and 51.0% in the period from 2017 to 2018. At least one complication occurred in 60.1% of the participants, and at least two complications occurred in 28.4%. Risk factors for the development of complications included minority race or ethnic group, hyperglycemia, hypertension, and dyslipidemia. No adverse events were recorded during follow-up.ConclusionsAmong participants who had onset of type 2 diabetes in youth, the risk of complications, including microvascular complications, increased steadily over time and affected most participants by the time of young adulthood. Complications were more common among participants of minority race and ethnic group and among those with hyperglycemia, hypertension, and dyslipidemia. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; ClinicalTrials.gov numbers, NCT01364350 and NCT02310724.).

Project description:Purpose of reviewTo provide an update on knowledge the role of genetics in youth-onset type 2 diabetes (T2D).Recent findingsThe prevalence in youth of T2D, once thought to be exclusively a disease of adults, has increased by over 35% since 2001. Youth with T2D tend to have higher rates of complications, more aggressive disease, with more rapid loss of beta-cell function and a less favorable response to treatment than adults. Obesity is the most important risk factor for T2D, and the rise in childhood overweight and obesity appears responsible for the dramatic increase in T2D in youth. However, some obese children do not develop T2D, consistent with genetic differences in susceptibility to the disease in the setting of obesity and insulin resistance, currently far less well characterized in youth than in adults. Recent studies have begun to show associations of several established adult T2D genetic risk variants with youth-onset T2D and related glycemic quantitative traits, including the strongest known cross-population T2D genetic contributor TCF7L2. Maturity-onset diabetes of the young (MODY), a diabetes subtype distinct from type 1 diabetes (T1D) and T2D, is now known to result from a highly penetrant gene mutation in one of several genes. MODY has been shown to account for or contribute to at least 4.5% of clinically diagnosed T2D, even among those who are overweight or obese, impacting treatment decisions. The recently formed ProDiGY (Progress in Diabetes Genetics in Youth) Consortium is using genome-wide association studies and whole exome sequencing to understand the genetic architecture of T2D in youth, including how it differs from that of adults. The limited amount of research conducted to date on the genetics of youth-onset T2D, which tends to be a more aggressive disease than adult T2D, suggests some overlap with genes involved in adult T2D and a sizeable influence of highly penetrant monogenic diabetes variants. The ProDiGY Consortium is expected to provide a more comprehensive understanding of youth T2D genetics.

Project description:BackgroundAlthough cumulating evidence has suggested that early-onset type 2 diabetes mellitus (T2DM) conferred on patients a broader tendency for complications beyond vascular ones, a comprehensive analysis of patterns of complications across all relevant systems is currently lacking.MethodWe prospectively studied 1 777 early-onset (age at diagnosis ≤ 45 years) and 35 889 late-onset (>45 years) T2DM patients with matched unexposed individuals from the UK Biobank. Diabetes-specific and -related complications were examined using phenome-wide association analysis, with patterns identified by comorbidity network analysis. We also evaluated the effect of lifestyle modifications and glycemic control on complication development.ResultsThe median follow-up times for early-onset and late-onset T2DM patients were 17.83 and 9.39 years, respectively. Compared to late-onset T2DM patients, patients with early-onset T2DM faced a significantly higher relative risk of developing subsequent complications that primarily affected sense organs [hazard ratio (HR) 3.46 vs. 1.72], the endocrine/metabolic system (HR 3.08 vs. 2.01), and the neurological system (HR 2.70 vs. 1.81). Despite large similarities in comorbidity patterns, a more complex and well-connected network was observed for early-onset T2DM. Furthermore, while patients with early-onset T2DM got fewer benefits (12.67% reduction in pooled HR for all studied complications) through fair glycemic control (median HbA1c ≤ 53 mmol/mol) compared to late-onset T2DM patients (18.01% reduction), they seemed to benefit more from favorable lifestyles, including weight control, healthy diet, and adequate physical activity.ConclusionsOur analyses reveal that early-onset T2DM is an aggressive disease resulting in more complex complication networks than late-onset T2DM. Aggressive glucose-lowering intervention, complemented by lifestyle modifications, are feasible strategies for controlling early-onset T2DM-related complications.

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Youth-onset type 2 diabetes mellitus: an urgent challenge.

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Youth-onset type 2 diabetes mellitus: an urgent challenge.

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