Young-Onset Diabetes in East Asians: From Epidemiology to Precision Medicine

Abstract

Precision diagnosis is the keystone of clinical medicine. In East Asians, classical type 1 diabetes is uncommon in patients with youngonset diabetes diagnosed before age of 40, in whom a family history, obesity, and beta-cell and kidney dysfunction are key features. Young-onset diabetes affects one in five Asian adults with diabetes in clinic settings; however, it is often misclassified, resulting in delayed or non-targeted treatment. Complex aetiologies, long disease duration, aggressive clinical course, and a lack of evidence-based guidelines have contributed to variable care standards and premature death in these young patients. The high burden of comorbidities, notably mental illness, highlights the numerous knowledge gaps related to this silent killer. The majority of adult patients with youngonset diabetes are managed as part of a heterogeneous population of patients with various ages of diagnosis. A multidisciplinary care team led by physicians with special interest in young-onset diabetes will help improve the precision of diagnosis and address their physical, mental, and behavioral health. To this end, payors, planners, and providers need to align and re-design the practice environment to gather data systematically during routine practice to elucidate the multicausality of young-onset diabetes, treat to multiple targets, and improve outcomes in these vulnerable individuals.

Keywords: East Asians; Epidemiology; Precision medicine; Young-onset diabetes.

Fig. 1.

Histograms and superimposed component curves showing the bimodal distribution of 2-hour plasma glucose in Pima Indians. Adapted from Rushforth et al. [18], with permission from American Diabetes Association.

Fig. 2.

Associations of beta-cell function, expressed by homeostasis model assessment (HOMA2-beta%), with a family history of diabetes, number of affected family members, and body mass index (BMI) in patients with type 2 diabetes (upper panel), as well as the cross-sectional decline of beta-cell function with disease duration stratified by obesity in patients with young-onset diabetes (YOD) versus later-onset diabetes (LOD) (lower panel). Adapted from Fan et al. [34].

Fig. 3.

A conceptual framework where a complex disease like diabetes can be due to different causal mechanisms made up of different components, including but are not limited to genetic, epigenetic, life-course, autoimmune, environmental, socioeconomic, psychological, and behavioral factors, and other coexisting conditions, which may contribute to the marked phenotypic heterogeneity of young-onset diabetes. Adapted from Chan et al. [63]; Rothman et al. [70]; and Dagogo-Jack [73]. LADA, latent autoimmune diabetes in adults; MODY, maturityonset diabetes of the young.

Fig. 4.

The Hong Kong Diabetes Surveillance Database showing declining death rates (A, B) and standard mortality ratios in all age groups in patients with type 2 diabetes in 2001 to 2016 in men and women, except for the 20 to 44 age group (C, D). (E) It shows the declining proportions of patients with diabetes with poor glycaemic control, as indicated by glycated haemoglobin (HbA1c) ≥9%, with the least improvement in the 20 to 44 age group. Adapted from Yang et al. [69]; and Wu et al. [89], with permission from Springer Nature. CI, confidence interval. aAverage annual percent change is significantly different from zero at the alpha=0.05 level.

Fig. 5.

(A) The increasing hospitalization rates due to multiple morbidities in patients with young-onset diabetes from diagnosis until the age of 70 with mental illness, mainly due to depression, as a major cause of hospitalization during the earlier clinical course. (B) The estimated cumulative hospitalization rate by the age of 70 years in a person diagnosed with type 2 diabetes at age of 33 years and the reduction in hospitalization days by intensive control of multiple risk factors and delaying the onset of diabetes. Adapted from Ke et al. [87], with permission from American College of Physicians. aTargets of intensified management include glycated haemoglobin of 6.2%, systolic blood pressure of 120 mm Hg, low-density lipoprotein cholesterol level of 2.0 mmol/L (77.3 mg/dL), triglyceride level of 1.3 mmol/L (115.1 mg/dL), waist circumference of 85 cm (men) or 80 cm (women), and smoking cessation.

Fig. 6.

A conceptual framework explaining (A) how reduced endowment of beta-cell mass or function due to genetic factors may predispose individuals to earlier age of diagnosis of diabetes given the same trajectory of beta-cell function decline with same metabolic stress; (B) how increasing metabolic stress can cause accelerated decline in beta-cell function to bring forward the age of diagnosis; and (C) how by changing lifestyles and using medications to control multiple risk factors may delay the progressive decline in beta-cell function and delay the use of insulin and development of complications. Adapted from Chan et al. [63].