SAN FRANCISCO — Young people who were diagnosed with type 2 diabetes in their early teens had an "alarming" high rate of diabetes-associated complications by the time they were in their mid-20s, according to new research.
Moreover, among more than 500 young participants in the Longitudinal Outcomes in Youth With Type 2 Diabetes (TODAY-2) study, five died of various causes, mostly related to their diabetes within about 7.5 years of being diagnosed.
"Cardiovascular risk factors are highly prevalent in the population, target organ damage is evident, and serious cardiovascular events are occurring at rates unexpected for age [around mid-20s]," Philip S. Zeitler, MD, PhD, professor of pediatrics-endocrinology, University of Colorado School of Medicine, Aurora, lead investigator of the TODAY studies, concluded during a press briefing here at the American Diabetes Association (ADA) 2019 Scientific Sessions.
In addition, a number of the girls subsequently became pregnant — pregnancy complications were exceptionally high as was neonatal morbidity, compared with background rates for girls of the same age in the general population.
"The bottom line," Zeitler told Medscape Medical News, "is that many of these kids have a very rapid course both in terms of loss of glycemic control as well as development of complications."
"So as opposed to the usual pediatric approach of 'Well, let's hold off and not give additional medications'...I think we need to recognize that, in fact, in these younger kids we probably need even more aggressive management than many adults with type 2 diabetes.
"They have more aggressive disease and they're going to be living with the burden of cardiovascular disease hopefully for 50 years, so I think the take-home message is we need not hesitate to treat these kids aggressively."
The press briefing moderator, Alvin C. Powers, MD, Vanderbilt University Medical Center, Nashville, Tennessee, agreed that the findings are extremely distressing.
No one would have expected these rates of eye, heart, nerve, kidney, and pregnancy complications within a relatively short duration of diabetes, he told Medscape Medical News.
"It's very alarming about their health in the next 10 or 15 years," he said, "because we don’t have good therapy for that and we don't [quite] know what to do."
The five deaths were from myocardial infarction, renal failure, sepsis, post-operative cardiac arrest, and an overdose, said Zeitler. And just in the previous week, one of the study participants at their center who was just 26 years old needed triple heart bypass surgery.
"Taken together," he summarized, "these rates illustrate the serious personal and public health circumstances as these young adults enter what should be the most productive period of their lives."
Certainly, the course of type 2 diabetes diagnosed in youth is different from that diagnosed in adults, he stressed. "Research is urgently needed to better understand the reasons for the more serious trajectory in youth-onset type 2 diabetes," he said.
Heart, Kidney, Eye, Nerve, and Pregnancy Complications
Zeitler explained that the original TODAY trial enrolled 699 adolescents age 10 to 17 (mean age, 14) who were newly diagnosed with type 2 diabetes between 2004 to 2011 at 15 centers.
The participants were racially and ethnically diverse — Hispanic (40%), black (33%), white (21%), or other race/ethnicity (7%) — and two thirds were female.
The results of TODAY, published in the New England Journal of Medicine in 2012, showed that type 2 diabetes "was more aggressive in kids than in adults" and that the participants had a rapid loss of beta-cell function.
When the TODAY study ended in 2011, 572 participants who were a mean age of 18 entered phase 1 of the TODAY-2 follow-up study at the same study sites, which lasted 3 years.
Then 517 participants who were a mean age of 21 in 2014 stayed on in phase 2 of the TODAY-2 study during which they received care in the community.
Now in 2019, the participants are a mean age of 25 and have had type 2 diabetes for a mean of 7.5 years, and in some cases, up to 12 years.
On average, at the start of the TODAY study, participants had a body mass index (BMI) of 34.9 kg/m2 and an HbA1c of 6.0%.
At the start of TODAY-2, they had a BMI of 36.3 kg/m2 and an HbA1c of 9.3%.
The rates of complications increased steadily over the years following the initial diagnosis of youth-onset type 2 diabetes.
During the up to 12 years of follow-up, the cumulative incidence of elevated LDL cholesterol increased from 3% to 26%, and the cumulative incidence of hypertension increased from 20% to 55%.
Echocardiography performed at the end of the TODAY study and again in TODAY-2 detected abnormal results in 30% of the participants.
During follow-up there were 38 adjudicated cardiovascular events — arrhythmias, myocardial infarctions, heart failure, left ventricular dysfunction, deep vein thrombosis, vascular insufficiency, strokes, or transient ischemic attacks — in 19 patients, for a rate of 6.2 cardiovascular events/1000 patients/year.
The prevalence of abnormal albumin excretion increased from 8% at baseline to 42%, and the prevalence of hyperfiltration increased from 12% to 55%.
There were four adjudicated renal events: two patients had both chronic kidney disease and end-stage kidney disease, equal to 0.7 kidney disease events/1000 patients/year.
And among the 370 participants who had fundus photos taken in 2011 and 2018, there was "substantial" progression of diabetic retinopathy.
For example, 14% of TODAY participants had mild nonproliferative diabetic retinopathy (NPDR), but about 6 years later, 22% of participants in TODAY-2 had mild NPDR.
None of the patients in TODAY had macular edema, but 4% of patients in TODAY-2 developed it.
There were 142 adjudicated eye events — NPDR, proliferative diabetic retinopathy, macular edema, cataracts, and glaucoma — equal to 15.5 eye disease events/1000 patients/year.
Similarly, there were 14 adjudicated neuropathy events in 12 patients, equal to 2.3 neuropathy events/1000 patient-years, said Zeitler.
The prevalence of diabetic neuropathy, determined by an abnormal monofilament test, rose to 8% by year 12.
Diabetic retinopathy and neuropathy were more prevalent among participants who did not maintain glycemic control.
Disturbing Pregnancy, Maternal, and Neonatal Outcomes
From 2005 to 2019 there were 236 pregnancies with known outcomes among about 350 girls and young women.
Of these pregnancies, 11.9% ended in a miscarriage (compared with a national rate of 10%-15%), 3.8% of babies were stillborn (compared with 0.4%), and 23.7% of babies were premature (compared with 6.9%- 9.9%).
Babies' birth weights were also skewed, with 15.9% have a very low birth weight (compared with 8.3%), and conversely, 18.9% had macrosomia (birth weight > 4000 g) compared with 8.2% in the general population.
And 28.7% of babies had neonatal hypoglycemia (compared with 2.1%), 14.9% were in respiratory distress (7%), and 8.5% had a cardiac anomaly versus a rate of 1% in the general population.
In addition, 35.6% of the girls were hospitalized for maternal complications compared to 14% in the general population: 18.1% developed preeclampsia and 37.5% had maternal hypertension.
"The very high rates of maternal and offspring complications of pregnancy are disturbing," said Zeigler.
He said the TODAY researchers will be following the offspring of these girls to chart their progress.
The current study helped to inform new guidelines for managing patients with youth-onset type 2 diabetes, which acknowledge that the disease in youth is different; these were issued by ADA in December 2018, he concluded.
ADA 2019 Scientific Sessions. June 8, 2019.
The TODAY studies are funded by the National Institutes of Health.