ESPE Yearbook of Paediatric Endocrinology

Lancet. 2025 Jun 28;405(10497):2313-2326. doi: 10.1016/S0140-6736(25)00830-X

Brief Summary: This paper highlights the alarming global rise in early-onset T2D, encompassing youth-onset (<18 years) and young-adult onset T2D (<40 years). It explores the multifactorial causes, including obesity, socioeconomic disadvantages, ethnicity, genetics, and early-life exposures, with an emphasis on the rapid disease progression, increased complications, and substantial health burden associated with early-onset T2D.

Comment: This first paper in a 3-part Lancet Series^1,2 provides a comprehensive overview of the epidemiology and risk factors driving the global rise of early-onset T2D. The authors present compelling evidence that early-onset T2D, encompassing youth-onset and young-adult onset, is no longer rare and is becoming a defining feature of the modern diabetes epidemic.

The authors emphasize major changes in the global landscape of T2D over recent decades. While T2D was once primarily a concern in high-income countries, a rapid rise is now observed worldwide, including in low- and middle-income countries. Early-onset T2D is particularly concerning, due to its longer duration across the lifespan and more aggressive clinical course, with higher rates of both microvascular and macrovascular complications.

Obesity remains the leading risk factor, but the threshold for developingT2D varies by ethnicity. Socioeconomic status plays a dual role. In high-income countries, early-onset T2D disproportionately affects lower-income groups, while in low- and middle-income countries rising affluence and urbanization contribute to increased risk. Prenatal factors, such as in utero exposure to maternal diabetes or undernutrition, may increase future risk of T2D through epigenetic programming, contributing to a vicious cycle of intergenerational metabolic risk. The authors advocate for better surveillance, earlier screening, ethnicity-specific definitions, and life-course approaches to prevention.

Key message: This article, along with the 2 subsequent papers on early-onset T2D, represents a crucial and timely contribution to our understanding of the evolving diabetes epidemic. Together, these papers effectively integrate global data, biological insights, socioeconomic perspectives, complications, and treatment approaches.