Youth-Onset Type 2 Diabetes Spurs Lots of Later Complications

A diagnosis of type 2 diabetes in adolescence set patients up for increased risks of a myriad of related complications in early adulthood, a follow-up of the TODAY study showed.

Of 500 youths diagnosed with type 2 diabetes, more than 60% experienced at least one related complication over 15 years of follow-up, reported Kimberly Drews, PhD, of the Biostatistics Center at George Washington University in Rockville, Maryland, and colleagues.

Nearly 30% of these patients — whose average age was 26 — experienced two diabetes-related complications, and 7.1% had three or more, the researchers noted in the New England Journal of Medicine.

They found that diabetic kidney disease was relatively common in patients with youth-onset type 2 diabetes, with a cumulative incidence rate of 54.8%. About a third of these patients also experienced some degree of nerve disease related to their diabetes.

Although only 13.7% experienced retinal disease during the first few years of their diabetes, this took a stark jump — up to 51% — by year 15. This included advanced stages of diabetic eye disease, with 8.8% having moderate-to-severe retinal changes and 3.5% having macular edema.

In addition, there was an unsurprisingly high incidence of cardiovascular complications among this population. Hypertension was the most commonly reported, with a cumulative incidence rate of 67.5% among patients after 15 years of follow-up, followed by dyslipidemia, with a cumulative incidence rate of 51.6%.

Racial and ethnic minorities saw higher risks for microvascular complications, with Hispanic and Black patients having a significantly higher risk compared with white patients.

In an adjusted model, every 1% increase in glycated hemoglobin (HbA1c) was tied to an 18% higher risk for developing a complication (HR 1.18, 95% CI 1.14-1.22), the authors noted.

“The reason for the high incidence of complications in youth-onset type 2 diabetes is unknown, but it is most likely related to the extreme metabolic phenotype (which includes severe insulin resistance and rapid worsening of beta-cell function) and to challenging socioeconomic circumstances,” they pointed out.

Drews and colleagues noted that complications among their cohort were closely tied to hyperglycemia, insulin resistance, hypertension, and dyslipidemia.

This emphasizes a need for greater pharmacologic options for these pediatric patients, they continued. Currently, only insulin, metformin, and two GLP-1 receptor agonists, including once-daily injectable liraglutide (Victoza) and once-weekly exenatide extended-release (Bydureon BCise), are FDA approved for youths with type 2 diabetes. Liraglutide was approved for pediatric patients ages 10 and up in 2019, and exenatide only just gained this expanded indication last week.

These findings clearly indicate the need for SGLT2 inhibitors — including canagliflozin (Invokana), empagliflozin (Jardiance), dapagliflozin (Farxiga), and ertugliflozin (Steglatro) — to gain expanded indications for this younger patient population, Drews and team added.

Another therapeutic option that should be given more consideration in this population is metabolic surgery, they suggested, referencing the findings of the Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS) study, which showed a greater reduction in kidney disease in youths with diabetes versus adults.

Study Details

In 2011, the multicenter TODAY2 trial enrolled 572 participants from the original TODAY study. In the first phase (March 2011 through February 2014), patients were treated with metformin with or without insulin. From March 2014 through January 2020, 518 of these participants were transitioned into the observational phase, which was marked by annual follow-up visits. During this time, treatment of diabetes was fully managed by the patient’s own healthcare provider.

At baseline, all participants were between the ages of 10 to 17 years.

Because this was an extension of the TODAY trial, which included a 3-year period in which participants received intensive diabetes management, the researchers pointed out that this might have reduced the number of complications seen during follow-up.