Youth Type 2 Diabetes Linked to a Higher Risk of Diabetes-Related Complications

Does early-onset type 2 diabetes in youth put these patients at a higher risk of developing comorbidities as they become adults?

New cases of youth-onset type 2 diabetes (T2D) have increased alongside an increased number of children with obesity in the United States. In youth-onset T2D, insulin resistance and deterioration of beta-cell function advance more rapidly, resulting in worse glycemic control and increased risk of early diabetes-related complications.

The TODAY study enrolled 699 participants, ages 10 to 17, from 15 centers across the United States. The TODAY2 study enrolled 572 participants from the TODAY study and was a prospective observation of participants for an estimated 10.2 years. TODAY2 included annual study visits, but their health care provider provided medical management.

Percentage means and standard deviations represented glycemic control, demographic, metabolic, and non-metabolic characteristics. The Kaplan-Meier statical analysis was used in this study to estimate all cumulative incidences. A Cox-proportional hazard regression model was used to estimate the overall risk of any microvascular complication. The Cox model included fixed or time-varying covariates. In the TODAY2 study, the medication regimen consists primarily exclusively of insulin and metformin, with half the patients being prescribed both insulin and metformin at the same. One-quarter of the participants were on no medication.

Participants with glycated hemoglobin levels in the nondiabetic range decreased from 75% to 19% at the end of the study. The glycated hemoglobin level of at least 10% was 0% at baseline, but at 15 years increased to 34%. Hypertension cumulative incidences increased by 48.3%. Dyslipidemia increased by 30.8%. In 2010 or 2011, 13.7% of patients had very mild non-proliferative diabetic retinopathy. Seven years later, 51.0% had eye disease, 8.8% had moderate to severe retinal changes, and 3.5% had macular edema. 80.1% had microvascular complications at 15 years. Patients with kidney disease at baseline was 8.0%; at the end of the study, the cumulative incidence was 54.8%. Patients with nerve disease at baseline was 1.0%, at 15 years, the cumulative incidence was 32.4%. Minority race or ethnic group, high blood sugar, high BMI, low insulin sensitivity, hypertension, and dyslipidemia are all factors that increase the risk for diabetes-related complications. BMI was not a risk factor after adjustment for sex, race and ethnic group, age, and diabetes duration at randomization.

The data suggests that diabetes-related complications accumulate rapidly and occur earlier in youth-onset type 2 diabetes; 60.1% of participants had at least one microvascular complication. 28.4% of participants had a cluster of diabetes-related complications at a mean age of 26.4, with a mean time of occurrence of 13.3 years. It is unknown why youth-onset T2D has a rapid onset, but it is likely linked to extreme metabolic phenotyping and challenging socioeconomic circumstances. This study showed a strong correlation between complications and hyperglycemia, insulin resistance, hypertension, and dyslipidemia. Youth-onset type 2 diabetes has a suboptimal response to currently approved medication therapies. Treatment options for youth-onset T2D approved by the Food and Drug Administration (FDA) are insulin and metformin, with the recent addition of glucagon-like peptide-1 (GLP-1). Sodium-glucose cotransporter 2 (SGLT2) is not FDA approved for youth-onset type 2 diabetes. Metabolic bariatric surgery results in long-lasting weight loss and glycemic control in most patients. Bariatric surgery has shown to have better effects on glycemic and nonglycemic outcomes than medical therapy. The Teen-LABS Study showed that bariatric surgery had a greater regression and earlier attenuation of kidney disease in youth with type 2 diabetes than in adults.

Further studies should look into early aggressive management of blood sugar and risk factors associated with youth onset T2D. It is essential to understand the health care needs and usage patterns of young adults with youth onset type 2 diabetes to meet their needs 

Practice Pearls:

• There are currently three drugs FDA approved for youth onset type 2 diabetes (insulin, metformin, and glucagon-like peptide 1 agonist).
• There was an increase from baseline for all diabetes-related complications looked at in study as participants became adults.
• Bariatric surgery showed to benefit patients better than medical therapy in patients with overweight and youth onset type 2 diabetes.

“Long-Term Complications in Youth-Onset Type 2 Diabetes.” NEJM,  June 20211): 416-426. doi:10.1056/NEJMoa2100165

Jerrine Fletcher, Doctor of Pharmacy Candidate, Florida A&M University College of Pharmacy and Pharmaceutical Sciences