Age at diagnosis, glycemic trajectories, and responses to oral glucose-lowering drugs in type 2 diabetes in Hong Kong: A population-based observational study

Autoři: Calvin Ke aff001;  Thérèse A. Stukel aff003;  Baiju R. Shah aff002;  Eric Lau aff001;  Ronald C. Ma aff001;  Wing-Yee So aff001;  Alice P. Kong aff001;  Elaine Chow aff001;  Juliana C. N. Chan aff001;  Andrea Luk aff001
Působiště autorů: Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong SAR, China aff001;  Department of Medicine, University of Toronto, Canada aff002;  Institute of Health Policy, Management and Evaluation, University of Toronto, Canada aff003;  ICES, Toronto, Canada aff004;  Department of Medicine, Sunnybrook Health Sciences Centre, Toronto, Canada aff005;  Asia Diabetes Foundation, Metropole Square, Shatin, Hong Kong SAR, China aff006;  Hong Kong Institute of Diabetes and Obesity and Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong SAR, China aff007
Vyšlo v časopise: Age at diagnosis, glycemic trajectories, and responses to oral glucose-lowering drugs in type 2 diabetes in Hong Kong: A population-based observational study. PLoS Med 17(9): e32767. doi:10.1371/journal.pmed.1003316
Kategorie: Research Article
doi: 10.1371/journal.pmed.1003316



Lifetime glycemic exposure and its relationship with age at diagnosis in type 2 diabetes (T2D) are unknown. Pharmacologic glycemic management strategies for young-onset T2D (age at diagnosis <40 years) are poorly defined. We studied how age at diagnosis affects glycemic exposure, glycemic deterioration, and responses to oral glucose-lowering drugs (OGLDs).

Methods and findings

In a population-based cohort (n = 328,199; 47.2% women; mean age 34.6 and 59.3 years, respectively, for young-onset and usual-onset [age at diagnosis ≥40 years] T2D; 2002–2016), we used linear mixed-effects models to estimate the association between age at diagnosis and A1C slope (glycemic deterioration) and tested for an interaction between age at diagnosis and responses to various combinations of OGLDs during the first decade after diagnosis. In a register-based cohort (n = 21,016; 47.1% women; mean age 43.8 and 58.9 years, respectively, for young- and usual-onset T2D; 2000–2015), we estimated the glycemic exposure from diagnosis until age 75 years.

People with young-onset T2D had a higher mean A1C (8.0% [standard deviation 0.15%]) versus usual-onset T2D (7.6% [0.03%]) throughout the life span (p < 0.001). The cumulative glycemic exposure was >3 times higher for young-onset versus usual-onset T2D (41.0 [95% confidence interval 39.1–42.8] versus 12.1 [11.8–12.3] A1C-years [1 A1C-year = 1 year with 8% average A1C]). Younger age at diagnosis was associated with faster glycemic deterioration (A1C slope over time +0.08% [0.078–0.084%] per year for age at diagnosis 20 years versus +0.02% [0.016–0.018%] per year for age at diagnosis 50 years; p-value for interaction <0.001). Age at diagnosis ≥60 years was associated with glycemic improvement (−0.004% [−0.005 to −0.004%] and −0.02% [−0.027 to −0.0244%] per year for ages 60 and 70 years at diagnosis, respectively; p-value for interaction <0.001). Responses to OGLDs differed by age at diagnosis (p-value for interaction <0.001). Those with young-onset T2D had smaller A1C decrements for metformin-based combinations versus usual-onset T2D (metformin alone: young-onset −0.15% [−0.105 to −0.080%], usual-onset −0.17% [−0.179 to −0.169%]; metformin, sulfonylurea, and dipeptidyl peptidase-4 inhibitor: young-onset −0.44% [−0.476 to −0.405%], usual-onset −0.48% [−0.498 to −0.459%]; metformin and α-glucosidase inhibitor: young-onset −0.40% [−0.660 to −0.144%], usual-onset −0.25% [−0.420 to −0.077%]) but greater responses to other combinations containing sulfonylureas (sulfonylurea alone: young-onset −0.08% [−0.099 to −0.065%], usual-onset +0.06% [+0.059 to +0.072%]; sulfonylurea and α-glucosidase inhibitor: young-onset −0.10% [−0.266 to 0.064%], usual-onset: 0.25% [+0.196% to +0.312%]). Limitations include possible residual confounding and unknown generalizability outside Hong Kong.


In this study, we observed excess glycemic exposure and rapid glycemic deterioration in young-onset T2D, indicating that improved treatment strategies are needed in this setting. The differential responses to OGLDs between young- and usual-onset T2D suggest that better disease classification could guide personalized therapy.

Klíčová slova:

Diabetes diagnosis and management – diabetes mellitus – Gestational diabetes – Hong Kong – Insulin – Observational studies – Type 2 diabetes


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