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Page 128 Chan et al. J Transl Genet Genom 2024;8:13-34 https://dx.doi.org/10.20517/jtgg.2023.36

Table 2. Lifecourse factors that may influence the onset, trajectory, and consequences of diabetes (also refer to Figure 3)
Infancy and childhood Adolescence Middle age Old age
• Ethnicity and migration • Childhood illness (e.g., • Obesity, metabolic syndrome, and • Micro/macrovascular
• Common and rare genetic variants malignancy and steroid use) fatty liver complications
• Other familial factors • Childhood obesity • Lifestyles (e.g., unhealthy diet, • Chronic kidney disease
(e.g., hemoglobinopathy, chronic • Formation of habits and physical inactivity, poor sleep) • Heart failure
hepatitis B infection) lifestyles • Psychosocial stress • Cancer
• Epigenetics and perinatal • Education •Other risk conditions • Dementia

development • Socioeconomic status (e.g., depression, gestational diabetes, • Frailty
• Low birth weight PCOS, …)
• Endocrinopathy and drug use

Figure 4. A conceptual diagram showing the complex interactions between nature and nurture where multiple lifecourse factors can
predispose, precipitate, and perpetuate the onset and trajectories of diabetes resulting in markedly different outcomes, strongly
influenced by genetic factors, early childhood development, environmental exposures, lifestyles, and access to care and education
(reproduced with permission from GemVCare) [151] .

and bring forward the age of onset of diabetes. Other familial factors, such as chronic hepatitis B infection
and hemoglobinopathy, have been associated with diabetes in some ethnic groups [94,140] . Medical histories
such as pancreatic disease, gestational diabetes, polycystic ovary syndrome, thyroid disease, tuberculosis,
and mental illness may provide clues regarding the predisposition, precipitation, and perpetuation of
YOD [71,141,142] . A family history of diabetes affecting multiple generations with or without syndromic features
may alert the possibility of MODY or monogenic diabetes . Understanding patient-reported outcome
[67]
measures (PROMs) such as quality of life, competing priorities, psychosocial stress from work or family,
interpersonal relationships, and life events may help care providers address negative emotions,
[143]
maladjustment, and poor adherence frequently encountered in young patients with diabetes [101,144-146]
[Figure 3 and 4, Table 2].

PRACTICE ENVIRONMENT, CLINICAL ACUMEN AND PERSON-ORIENTATED CARE
A correct diagnosis is key to a meaningful dialogue between doctors and patients for informed and shared
decision-making [147,148] . This can only be achieved through comprehensive profiling, good doctor-patient
relationships, regular reviews, and quality care. However, the busy working environment, short consultation