T2D More Prevalent Than T1D Among Adolescents in Some Areas

In several countries, including China, Mexico, and the United States, the incidence of type 2 diabetes now exceeds that of type 1 diabetes among patients younger than 20 years.

“This is an emerging epidemic,” said Orit Pinhas-Hamiel, MD, director of the Pediatric Endocrinology and Diabetes Unit at Sheba Medical Center in Ramat Gan, Israel, at the European Association for the Study of Diabetes Annual Meeting (EASD) 2024, noting that these young patients, most with obesity, exhibit a significantly higher incidence of complications than adults with type 2 diabetes or young people with type 1 diabetes.

According to data from the United States, in 2017-2018, the incidence of type 2 diabetes among patients aged 15-19 years (19.7 per 100,000) surpassed that of type 1 diabetes (14.6 per 100,000).

“This is the first time that the incidence of type 2 diabetes has exceeded that of type 1 among youth,” said Pinhas-Hamiel. A review published a few months ago highlighted this surge, with countries like China, India, the United States, Brazil, and Mexico leading the way (2021 data).

SEARCH and TODAY

The SEARCH for Diabetes in Youth study, which was launched in 2000, is a multicenter observational study in the United States aimed at estimating the prevalence, incidence, and complications of types 1 and 2 diabetes among young patients. The Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study is an interventional study focusing on adolescents with type 2 diabetes to evaluate the effectiveness of various treatment options.

“Diabesity” — the dual global epidemic of obesity and type 2 diabetes — has visible consequences from the moment of diagnosis, including hypertension. In the TODAY study, 11.6% adolescents had hypertension at diagnosis. A study conducted in Hong Kong involving 391 children younger than 18 years revealed that 22.5% had hypertension. In SEARCH, 27% young patients diagnosed with type 2 diabetes for 1.5 years had hypertension.

In addition, the SEARCH study found that 27% young individuals had low levels of high-density lipoprotein cholesterol, while 25% had high triglyceride levels, at 1.5 years after diagnosis.

Overall, the cumulative incidence of long-term diabetic complications was assessed in 500 adolescents participating in TODAY (mean age, 26.4 ± 2.8 years; mean time since diagnosis, 13.3 ± 1.8 years). The initial prevalence was 19.2%, while the cumulative incidence rose to 67.5% after 15 years of follow-up.

For dyslipidemia, the initial prevalence was 20.8%, with a cumulative incidence of 51.6%. The incidence of diabetic nephropathy was 54.8% and neuropathies was 32.4%. The prevalence of retinopathy was 13.7% for the period 2010-2011 and 51% for 2017-2018.

At least one complication was observed in 60.1% participants and at least two in 28.4%. As expected, risk factors for developing complications included belonging to a racial or ethnic minority, hyperglycemia, hypertension, and dyslipidemia.

“Among those who developed type 2 diabetes in adolescence, the risk for complications, including microvascular complications, has continuously increased and affected most participants in young adulthood,” said Pinhas-Hamiel.

At the same time, the rate of treatment with lipid-lowering and antihypertensive medications remains low among young people with type 2 diabetes. The management of dyslipidemia is suboptimal, with only 5% young patients with diabetes and dyslipidemia receiving appropriate medications. Furthermore, treatment adherence is lacking. In the TODAY cohort, for example, only one third of participants with high levels of low-density lipoprotein cholesterol were on lipid-lowering medications, and only half of the young patients with hypertension were taking antihypertensives.

Focus on Diabetic Nephropathy

Diabetic kidney disease is the leading microvascular complication of type 2 diabetes in adolescents. It is associated with rapid progression and poor prognosis. The natural history begins with hyperfiltration: A consequence of obesity and impaired glucose tolerance. Structural renal changes can be detected as early as 1.5 years after diagnosis.

The second stage is characterized by a reduction in the glomerular filtration rate. At this stage, “the structural changes in the kidney are typical but often present,” said Pinhas-Hamiel, making this period critical for reducing risk factors.

In TODAY, the cumulative incidence of diabetic nephropathy was 54.8%. The prevalence at inclusion was 8%. In SEARCH, after 8 years, the prevalence of diabetic kidney disease was 19.9% among adolescents with type 2 diabetes vs 5.8% among those with type 1 diabetes. A pre-analysis revealed that the overall prevalence of macroalbuminuria among 730 children and adolescents with type 2 diabetes was 3.8%. The ages at diagnosis of type 2 diabetes ranged from 6.5 to 21 years, and the duration of the disease varied from diagnosis to 15 years after.

Diabetic retinopathy was present in 50% participants in the TODAY study at age 25 years (ie, after 12 years of disease). In SEARCH, 56% young patients had diabetic retinopathy after 12.5 years of diabetes. In addition, in the same study, the prevalence of peripheral neuropathy, assessed after 8 years, was 22% among adolescents with type 2 diabetes vs 7% among those with type 1 diabetes.

Cardiovascular Autonomic Neuropathy

A decrease in heart rate variability was observed in 47% young patients with type 2 diabetes after an average disease duration of only 1.7 years. In SEARCH, the prevalence of cardiovascular autonomic neuropathy, assessed after 8 years of disease, was 17% in adolescents with type 2 diabetes vs 12% in those with type 1 diabetes.

Overall, 7.1% participants had three complications: Nephropathy, retinopathy, and neuropathy. The cumulative incidence of microvascular complications was 80%.

Moreover, A1c levels deteriorated progressively throughout the follow-up period. Approximately 45% participants had an A1c of at least 10%, and 20% were between 8% and 10%. Body mass index consistently remained between 35 and 37.5.

Young patients with type 2 diabetes exhibit endothelial dysfunction, increased carotid intima-media thickness, elevated arterial stiffness, left ventricular hypertrophy, diastolic dysfunction, and reduced maximal exercise capacity. All these factors predict cardiovascular morbidity and mortality.

In TODAY, 17 serious cardiovascular events were recorded, including four myocardial infarctions, six cases of congestive heart failure, three coronary events, and four strokes.

In an analysis of the TODAY and SEARCH studies, although the average duration of diabetes was similar, complications were more frequent among young patients with type 2 diabetes than among those with type 1 diabetes. Microvascular complications were 2.5 times more frequent, and macrovascular complications were four times more frequent.

In SEARCH, excessive mortality was observed among young adults for each type of diabetes. Differences in risk were associated with diabetes type, age, race/ethnicity, and sex. Mortality ratios were 1.5 and 2.3 for types 1 and 2 diabetes, respectively.

Women had higher mortality rates than men. Diabetes was the underlying cause of death in 9.1% cases, which was comparable to cardiovascular diseases or cancer (10.9%). According to a life expectancy model, young patients with type 2 diabetes lose about 15 years of life.

Eating Disorders and Depression

Beyond these complications, other issues are often present among adolescents with type 2 diabetes. Approximately 50% have eating disorders (compared with 21% among those with type 1 diabetes), 19.3% report depressive symptoms, and 18.9% have expressed thoughts of self-harm. In addition, 19.6% have polycystic ovary syndrome. Z-scores for bone mineral density at the femoral neck and lumbar spine were significantly lower in adolescents with type 2 diabetes than in healthy peers. The presence of metabolic dysfunction–associated fatty liver disease is also more pronounced.

“The recent approvals of new pharmacological interventions for weight loss and improved glycemic control in adolescents offer hope. We hope that over the next decade, the prevalence of complications among these young patients with type 2 diabetes will decline. In the meantime, a proactive approach is essential to prevent complications related to type 2 diabetes in these youth,” Pinhas-Hamiel concluded.

For more information, see ISPAD Clinical Practice Consensus Guidelines 2022: Type 2 Diabetes in Children and Adolescents.

Pinhas-Hamiel reported no relevant financial relationships.

This story was translated from the Medscape French edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.