development of complications in children diagnosed with youth - onset type 2 diabetes mellitus

Last edited 07/2021 and last reviewed 08/2021

The incidence of youth-onset type 2 diabetes has increased in parallel with the rise in the number of children with obesity in the United States

• in the period from 2002 to 2012, the incidence of type 2 diabetes increased by 4.8% each year
• pathologic processes associated with diabetes, including the development of insulin resistance and the deterioration of beta-cell function, progress more rapidly in youth-onset type 2 diabetes than in adult-onset diabetes
  • these factors result in worse glycemic control and an increased risk of early diabetes-related complications

The TODAY Study group 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

Results:

• at 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
• cumulative incidence of hypertension was 67.5%
• incidence of dyslipidemia was 51.6%
• incidence of diabetic kidney disease was 54.8%
• the incidence of nerve disease was 32.4%
• 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

The TODAY Study Group concluded that:

• among 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

Reference:

• Al-Saeed AH et al. An inverse relationship between age of type 2 diabetes onset and complication risk and mortality: the impact of youth-onset type 2 diabetes. Diabetes Care 2016; 39: 823-9.
• Dabelea D et al. Prevalence of type 1 and type 2 diabetes among children and adolescents from 2001 to 2009. JAMA 2014; 311: 1778-86.
• Mayer-Davis EJ et al. Incidence trends of type 1 and type 2 diabetes among youths, 2002-2012. N Engl J Med 2017; 376: 1419-29.
• TODAY Study Group. Long-Term Complications in Youth-Onset Type 2 Diabetes. N Engl J Med 2021; 385:416-426