The changing face of diabetes in youth: lessons learned from studies of type 2 diabetes

Abstract

The incidence of youth type 2 diabetes (T2D), linked with obesity and declining physical activity in high-risk populations, is increasing. Recent multicenter studies have led to a number of advances in our understanding of the epidemiology, pathophysiology, diagnosis, treatment, and complications of this disease. As in adult T2D, youth T2D is associated with insulin resistance, together with progressive deterioration in ␤ cell function and relative insulin deficiency in the absence of diabetes-related immune markers. In contrast to adult T2D, the decline in ␤ cell function in youth T2D is three-to fourfold faster, and therapeutic failure rates are significantly higher in youth than in adults. Whether the more aggressive nature of youth T2D is driven by genetic heterogeneity or physiology/metabolic maladaptation is yet unknown. Besides metformin, the lack of approved pharmacotherapeutic agents for youth T2D that target the pathophysiological mechanisms is a major barrier to optimal diabetes management. There is a significant need for effective therapeutic options, in addition to increased prevention, to halt the projected fourfold increase in youth T2D by 2050 and the consequences of heightened diabetes-related morbidity and mortality at younger ages.

Vascular and Endothelial Function in Youth with Type 2 Diabetes Mellitus

“…However, in parallel with increases in the rate of childhood obesity, type 2 diabetes has now emerged as a formidable threat to the health of adolescents [12]. T2D accounts for nearly 50% of new diabetes cases in adolescents and the incidence and prevalence continue to rise [13–16].…”

Youth-Onset Type 2 Diabetes Manifestations in other Specialties: Its Many Disguises

“…For some of these (microalbuminuria, hypertension, neuropathy, and mortality), the risk is increased with youth-onset T2D versus T1D [6]. Such complications may be evident within 2-5 years of T2D diagnosis [4,46], but they have also been recorded at diagnosis [24], making it important for HCPs to be aware of the overlap between the occurrence of the complication and the diagnosis of youth-onset T2D.…”

“…As with adult T2D, patients with youth-onset T2D are at risk of serious complications [6]. Microvascular, renal, and neurological complications may be evident 5 years post-diagnosis [4], with more serious complications such as blindness developing within 10 years from diagnosis [2]. These individual burdens combine to create a potentially large societal impact [3], particularly if the disease remains undetected and untreated.…”

“…These HCPs screen for diabetes regularly, but sometimes patients may be asymptomatic or mildly symptomatic for youth-onset T2D [7,8], or present with another condition obscuring T2D [4]. While there are classic symptoms and risk factors of youth-onset T2D [8,9], there are several other manifestations that could indicate whether it is appropriate to screen for this disease (Table 1).…”

“…Youth-onset T2D creates large personal and societal burdens [2,4]. For example, children and adolescents with T2D had reduced quality of life at the end of the 60-month SEARCH trial (compared with baseline and with participants with T1D) [5].…”