‘Shocking’ Early Complications of Type 2 Diabetes in Adolescence

July 30, 2021 – Newly released data shows alarming rates and severity of early complications specific to diabetes in people who develop Type 2 diabetes at an early age. This suggests that the intervention should be early and aggressive in these young people, one of the researchers said.

The results for the 500 young adults participating in the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY 2) study were published online July 28 in the New England Journal of Medicine by the TODAY Study Group.

At follow-up, after originally participating in the TODAY trial as young adolescents, they had a mean age of 26.4 years.

At that time, more than two-thirds had hypertension and half had dyslipidemia or high levels of cholesterol or fat in the blood.

Overall, 60% had at least one microvascular complication of diabetes (retinal disease, neuropathy or diabetic nephropathy), and more than a quarter had at least two of these complications.

“These data illustrate the serious consequences on personal and public health of the appearance of young Type 2 diabetes in the transition to adulthood, ”the researchers said.

Don’t walk lightly just because they’re kids

“The fact that these young people accumulate complications at a rapid rate and are widely affected in early adulthood certainly suggests that aggression therapy is necessary, both for blood sugar control and the treatment of risk factors such as hypertension and dyslipidemia, ”says study co-author Philip S. Zeitler, MD.

“In the absence of studies dealing specifically with this, we have to take a more aggressive approach than people might be inclined to do, given that the age at diagnosis is young, around 14,” says he.

“Contrary to the tendency to be ‘gentle’ when treating them because they are children, this data suggests that we cannot let those early years go by without strong intervention and we need to be prepared for polypharmacy.”

Unfortunately, as Zeitler and his co-authors explained, the appearance of young Type 2 diabetes is characterized by a suboptimal response to currently approved medical therapies for diabetes.

New pediatric indications in the United States for drugs used to treat type 2 diabetes in adults, including the recent Food and Drug Administration approval Extended-release exenatide for children as young as 10 years old, “helps, but only marginally,” says Zeitler, of the Clinical and Translational Research Center at Colorado Children’s Hospital, Aurora.

“In some cases this will help get them covered by carriers, which is always a good thing. But this is still a very limited set of drugs. It does not include the glucagon-like peptide-1. more potent approved more recently (GLP-1) agonists, such as semaglutide, and does not include sodium-glucose co-transporter 2 (SGLT2) inhibitors. Pediatricians are accustomed to using off-label drugs and this is necessary here in awaiting further approvals, ”he said.

In the United States, most people with early-onset type 2 diabetes are either covered by public insurance or uninsured, depending on the state they live in, he says. While the two big Medicaid Colorado programs allow full access to adult forms, which is not the case everywhere. Additionally, patients often face other barriers to access in states without extensive Medicaid.

Tracking shows all metrics worsen over time

In TODAY 2, patients participated in observational follow-up in their usual care setting in 2011-2020. At first they were given metformin with or without insulin for diabetes, but whether this continued and whether they were treated for other risk factors depended on individual circumstances.

The median A1c of participants increased over time, and the A1c percentage <6% (48 mmol / mol) fell from 75% at the time of entry TODAY to only 19% at the end of the 15-year follow-up.

The proportion with an A1c of 10% (86 mmol / mol) or more increased from 0% initially to 34% at 15 years.

At that time, almost 50% were taking both metformin and insulin, while more than a quarter were not taking any medication.

The prevalence of hypertension fell from 19.2% at baseline to 67.5% at age 15, while dyslipidemia fell from 20.8% to 51.6%.

Kidney disease the prevalence fell from 8.0% at baseline to 54.8% at 15 years. Nervous diseases fell from just 1.0% to 32.4%. Retinal disease increased from 13.7% with milder nonproliferative retinopathy in 2010-2011 to 51.0% with any eye disease in 2017-2018, including 8.8% with moderate to severe retinal changes and 3.5% with macular edema.

Overall, at the time of the last visit, 39.9% had no complications from diabetes, 31.8% had one, 21.3% had two, and 7.1% had three.

Serious cardiovascular events in your mid-twenties

There were 17 serious cardiovascular events judged, including four myocardial infarctions, six congestive heart failure events, three diagnoses of coronary heart disease and four strokes.

Six participants died, one each from a myocardial infarction, kidney drug failure and overdose, and three of sepsis.

Zeitler says the macrovascular events are “shocking,” noting that although the numbers are low, for people in their mid-twenties, “they should be zero … although we don’t yet know if the rates are the same. or faster than adults, even though they are the same, these kids are only in their late twenties, as opposed to adults who experience these issues in their fifties, sixties and sixties. ”

“The fact that these complications arise when these people should be in their prime, both for their families and for their work, has huge implications,” he says.

The results have multiple causes

The reasons for these results are both biological and socio-economic, he says.

“We already know that many children with type 2 have [deterioration of] beta cell [function], which is probably very biological. It goes without saying that an individual who can getting diabetes as a teenager probably has more fragile beta cells in one way or another.

“But we also know that a lot of other things contribute to it, [such as] stress, social determinants, access to quality care and medicines, access to healthy food and physical activity, availability of family support given the realities of the economic status and employment of families, etc. .

It is also known that young people with type 2 diabetes have much more severe insulin resistance than adults with the disease, and that “once the children are gone … [TODAY] study, the treatment of risk factors in the community was less than ideal, and many children who met criteria for treatment of their blood pressure or lipids were not processed. This is probably at least in part sociological and in part of the general pediatric reluctance to use drugs. “

He says the TODAY team will soon have new data to show that “blood sugar in the early years makes a difference, again supporting intensive intervention early on.”