Youth-onset type 2 diabetes mellitus—a distinct entity?

Abstract

Diabetes mellitus is a chronic and lifelong disease that causes a huge burden to the healthcare system. Its prevalence is increasing worldwide. Global estimates suggest that 463 million individuals have diabetes as of 2019 and that this number will increase to 700 million by 2045, whereas in India 77 million individuals have diabetes as of 2019 and this will increase to 134 million by 2045 [1]. Over 90% of cases of diabetes are of type 2 diabetes mellitus. The increase in the prevalence of diabetes among older adults is well recognised but the rising number of young people with type 2 diabetes is a more recent development and is of particular concern. Type 2 diabetes mellitus in adolescents and young adults results in adverse societal effects because of the presence of a chronic disease throughout patients’ working life and consequently greater propensity for long-term complications. Type 2 diabetes in young people could be more rapid and disruptive than in patients who have diabetes later in life, leading to early morbidity and poor quality of life [2]. There is a 31% increase in type 2 diabetes in age group 10–19 years in the USA between 2001 and 2009, resulting prevalence of 0·48 per 1000 in this age group [3]. Data from the SEARCH study [4] shows an annual increase of about 7% in the incidence of type 2 diabetes between 2002–2003 and 2011–2012 among people aged 10–19 years in the USA, with substantial relative increases in all ethnic minority groups compared with non-Hispanic White people. The registry of youth-onset diabetes in India (YDR) reported that over 25% of youth-onset diabetes less than 25 years were type 2 diabetes mellitus [5] with an incidence of 0.5 cases/100,000 in those under 19 years [6]. In those less than 19 years of age, type 2 diabetes was equally common in both genders with the mean duration of diabetes at the presentation of 7 years. Most of these patients belonged to the high socioeconomic group, over 57% were either overweight or obese and over 70% had HbA1C of more than 9% indicating poor control [7]. The prevalence of DKA among T2D in SEARCH and YDR was 5.5% and 6.6% respectively [8]. The development and progression of type 2 diabetes represent a complex interplay between genetic, epigenetic, lifestyle, demographic, socioeconomic, therapeutic and environmental factors. A majority of patients with type 2 diabetes have at least one parent with type 2 diabetes mellitus [9]. The mechanisms leading to the development of type 2 diabetes in young people are similar to those in older patients, but the speed of onset, severity and interplay of reduced insulin sensitivity and defective insulin secretion may be different in patients who develop type 2 diabetes at a younger age [10] and a better understanding of this would help in improvement in its management. Type 2 diabetes in young people was thought to be associated with chronic complications due to longer disease duration but now there is increasing evidence that the disease could have a faster rate of progression in young people. As seen with late-onset type 2 diabetes, adolescents also have initial deterioration in β-cell function which is characterised by loss of the first phase of stimulated insulin secretion [4]. There is some evidence that the second phase of nutrient-induced insulin secretion might be compromised earlier in younger individuals with type 2 diabetes [10]. TODAY study showed a 20–35% annual decline in β-cell function in adolescents aged 10–19 years with type 2 as compared to a 7% decline in older individuals with type 2 diabetes [11]. The prevalence of obesity among children, adolescents and young adults with type 2 diabetes is much greater than in older adults with type 2 diabetes and there is an inverse relationship between BMI and age at diagnosis of type 2 diabetes [12]. Physical inactivity is associated with an increased risk of obesity. The CARDIA study [13] which was a multicentre cohort study in 5115 participants aged 18–30 years showed that physical inactivity was strongly associated with risk of type 2 diabetes, hypertension and metabolic syndrome. Intrauterine environment can affect the development of obesity and type 2 diabetes in adolescents * S. V. Madhu [email protected]