Patients with youth-onset T2D have accelerated onset of hypertension, dyslipidemia, kidney disease, nerve disease, and diabetic retinopathy.
Patients who acquire type 2 diabetes during childhood develop insulin resistance and beta-cell degradation faster than those who acquire T2D in adulthood. An accelerated loss of glycemic control increases the risk of developing diabetes-related complications. A previous study from the SEARCH for Diabetes in Youth registry found a higher incidence of diabetic kidney disease, hypertension, retinal disease, and peripheral nerve disease among youth with T2D than those with T1D. Data from the Australian National Death Index and the Australian National Diabetes Services Scheme found an inverse relationship between the age at onset of T2D and the long-term risk of developing end-stage kidney disease. The lack of prospective longitudinal data has hindered the development of evidence-based guidelines in preventing and managing complications from youth-onset T2D.
From 2004 to 2011, phase one of the TODAY study evaluated the time to lose glycemic control in patients with youth-onset T2D. Participants took either Metformin, Metformin plus rosiglitazone, or Metformin coupled with intensive lifestyle intervention. Results found that adding a second pharmacologic medication was superior to Metformin alone in controlling high blood glucose. However, an intensive lifestyle intervention did not improve glycemic control since the change was difficult to maintain in the younger population. From 2011 to 2020, researchers of phase two TODAY2 Study conducted a longitudinal follow-up of 500 participants. Individuals were placed on Metformin, with or without insulin. Researchers performed assessments for diabetic kidney disease, hypertension, dyslipidemia, and nerve disease annually, and retinal disease twice.
The mean age was (26.4 ± 2.8 years), with the mean time since diagnosis of diabetes being (13.3 ± 1.8 years). Insulin and Metformin were taken almost exclusively, with nearly half the individuals taking both after the trial. More than a quarter took no medication after the trial. At baseline, some individuals had hypertension (19.2%), dyslipidemia (20.8%), kidney disease (8.0%), and nerve disease (1%). The cumulative incidence at fifteen years increased in hypertension (67.5%), dyslipidemia (51.6%), kidney disease (54.8%), and nerve disease (32.4%). Between 2010-2011, the incidence of very mild non-proliferative diabetic retinopathy was 13.7%. After seven years, an increase in the incidence of eye disease (51%), moderate to severe retinal changes (8.8%), and macular edema (3.5%) was noted. The cumulative incidence of any microvascular complication was 50.0% by nine years and 80.1% by fifteen years.
The number of complications associated with diabetes was recorded at the last visit: 39.9% had no complications, 31.8% had one, 21.3% had two, and 7.1% had three. Complications were more common among minorities and those with hyperglycemia, hypertension, and dyslipidemia. Cardiovascular severe events included myocardial infarction (4 people), congestive heart failure (6 people), coronary artery disease (3 people), and stroke (4 people). Death was reported from these causes; myocardial infarction (1 person), kidney failure (1 person), drug overdose (1 person), sepsis (1 person), and sepsis with multiorgan loss (2 people). No adverse events were reported at follow-up.
It was found that with time, individuals with youth-onset type 2 diabetes had an increased incidence of hypertension, dyslipidemia, kidney disease, nerve disease, and microvascular complications. Serious cardiovascular events and death also occurred in these young individuals. Researchers believe rapid insulin resistance, the decline in beta-cell function, and lower socioeconomics might play a role in worsened health outcomes. More research is needed to determine why this patient population declines more rapidly. This prospective longitudinal study had several weaknesses. First, a partial follow-up of the original cohort might have resulted in underrepresentation. Second, data on nicotine use, a significant cardiovascular risk factor, was collected but classified as unreliable. Also, the incidence of complications might have been higher if the participants did not receive free intensive disease management until 2014. Lastly, longitudinal data are absent on microvascular complications in adolescents with obesity who did not have diabetes.
- Individuals with youth-onset T2D had more rapid insulin resistance, faster beta-cell degradation, and earlier glycemic control loss than adult-onset diabetes.
- At baseline, there was an incidence of hypertension (19.2%), dyslipidemia (20.8%), kidney disease (8.0%), and nerve disease (1%). However, the cumulative incidence at fifteen years increased for hypertension (67.5%), dyslipidemia (51.6%), kidney disease (54.8%), and nerve disease (32.4%).
- While rare, serious cardiovascular events and death occurred in participants with youth-onset type 2 diabetes.
TODAY study Group et al. “Long-Term Complications in Youth-Onset Type 2 Diabetes.” The New England journal of medicine vol. 385,5 (2021): 416-426. doi:10.1056/NEJMoa2100165
Kornelia Iliasm Creighton University | School of Pharmacy and Health Professions Doctor of Pharmacy Candidate Class of 2022