medwireNews: The latest TODAY2 findings show rapid accumulation of cardiovascular risk factors and diabetes complications following a diagnosis of type 2 diabetes during childhood or adolescence.
Despite the study participants being an average age of just 21.2 years at the start of this second, 6-year phase of TODAY2 there were even a few incidences of “hard” clinical endpoints including myocardial infarction, end-stage kidney disease, and amputations.
“These kids are in their mid-20s and they’re having problems you’d expect from your grandparents”, researcher Philip Zeitler (University of Colorado, Aurora, USA) told press at the 79th ADA Scientific Sessions in San Francisco, California, USA.
There were also five deaths, including one from myocardial infarction and one from renal failure. The others related to sepsis, post-operative arrest, and overdose.
For this study phase, 517 of the original 699 TODAY participants were returned to routine community care, undertaking only annual study visits. Their average diabetes duration at this point was 7.5 years.
The prevalence of high low-density lipoprotein cholesterol rose from just 3% at original TODAY enrolment to 26% by the end of TODAY2 (a total 12-year follow-up). Baseline hypertension prevalence was 19% but approaching 60% by the end of follow-up.
Also, 30% had abnormal echocardiography findings by the study end, and there were a number of clinical events, including arrhythmia, coronary heart disease or myocardial infarction, and heart failure.
Although stressing that it is hard to directly compare cardiovascular event data in children versus adults, Zeitler said that the 38 total events gave a rate of 6.18 per 1000 person–years, which is “substantial” and broadly equivalent to that seen in older adults with type 1 diabetes participating in EDIC, the DCCT long-term follow-up.
Deteriorating renal status was also evident, with the prevalence of hyperfiltration rising from 12% to 55%, and increased albumin excretion from 8% to 42%.
Zeitler noted that the team also has evidence that estimated glomerular filtration rate is beginning to fall in these young patients. Indeed, there were two cases of chronic kidney disease and two of end-stage renal disease.
There was also “substantial progression” of retinopathy. At baseline, the study participants were largely free of eye disease, with very mild retinopathy present in 14%, but by the end of follow-up 49% had some form of retinopathy, up to and including high-risk proliferative diabetic neuropathy, with 9% needing intervention.
A little under 30% of the participants developed abnormal peripheral nerve function, and there were “a number of amputations likely related to vascular and nerve abnormalities”, said Zeitler, adding that “quite a number of toes are now missing in this group of kids”.
The researchers also saw poor pregnancy outcomes for the 236 pregnancies with known outcomes, including increased rates of stillbirth, preterm birth, low birthweight, large for gestational age, and neonatal and maternal complications.
“These results illustrate the serious personal and public health circumstances as these young adults enter what should be the most productive period of their lives”, concluded Zeitler.
By Eleanor McDermid
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79th ADA Scientific Sessions; San Francisco, California, USA: 7–11 June 2019