Obesity, clinical, and genetic predictors for glycemic progression in Chinese patients with type 2 diabetes: A cohort study using the Hong Kong Diabetes Register and Hong Kong Diabetes Biobank


Autoři: Guozhi Jiang aff001;  Andrea O. Luk aff001;  Claudia H. T. Tam aff001;  Eric S. Lau aff005;  Risa Ozaki aff001;  Elaine Y. K. Chow aff001;  Alice P. S. Kong aff001;  Cadmon K. P. Lim aff001;  Ka Fai Lee aff006;  Shing Chung Siu aff007;  Grace Hui aff007;  Chiu Chi Tsang aff008;  Kam Piu Lau aff009;  Jenny Y. Y. Leung aff010;  Man-wo Tsang aff011;  Grace Kam aff011;  Ip Tim Lau aff012;  June K. Li aff013;  Vincent T. Yeung aff014;  Emmy Lau aff015;  Stanley Lo aff015;  Samuel K. S. Fung aff016;  Yuk Lun Cheng aff017;  Chun Chung Chow aff001;  Ewan R. Pearson aff018;  Wing Yee So aff001;  Juliana C. N. Chan aff001;  Ronald C. W. Ma aff001;  ; 
Působiště autorů: Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China aff001;  Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Hong Kong, China aff002;  Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China aff003;  CUHK-SJTU Joint Research Centre in Diabetes Genomics and Precision Medicine, The Chinese University of Hong Kong, Hong Kong, China aff004;  Asia Diabetes Foundation, Hong Kong, China aff005;  Department of Medicine and Geriatrics, Kwong Wah Hospital, Hong Kong, China aff006;  Diabetes Centre, Tung Wah Eastern Hospital, Hong Kong, China aff007;  Diabetes and Education Centre, Alice Ho Miu Ling Nethersole Hospital, Hong Kong, China aff008;  North District Hospital, Hong Kong, China aff009;  Department of Medicine and Geriatrics, Ruttonjee Hospital, Hong Kong, China aff010;  Department of Medicine and Geriatrics, United Christian Hospital, Hong Kong, China aff011;  Tseung Kwan O Hospital, Hong Kong, China aff012;  Department of Medicine, Yan Chai Hospital, Hong Kong, China aff013;  Centre for Diabetes Education and Management, Our Lady of Maryknoll Hospital, Hong Kong, China aff014;  Department of Medicine, Pamela Youde Nethersole Eastern Hospital, Hong Kong, China aff015;  Department of Medicine and Geriatrics, Princess Margaret Hospital, Hong Kong, China aff016;  Department of Medicine, Alice Ho Miu Ling Nethersole Hospital, Hong Kong, China aff017;  Division of Population Health and Genomics, School of Medicine, University of Dundee, Dundee, Scotland, United Kingdom aff018
Vyšlo v časopise: Obesity, clinical, and genetic predictors for glycemic progression in Chinese patients with type 2 diabetes: A cohort study using the Hong Kong Diabetes Register and Hong Kong Diabetes Biobank. PLoS Med 17(7): e32767. doi:10.1371/journal.pmed.1003209
Kategorie: Research Article
doi: 10.1371/journal.pmed.1003209

Souhrn

Background

Type 2 diabetes (T2D) is a progressive disease whereby there is often deterioration in glucose control despite escalation in treatment. There is significant heterogeneity to this progression of glycemia after onset of diabetes, yet the factors that influence glycemic progression are not well understood. Given the tremendous burden of diabetes in the Chinese population, and limited knowledge on factors that influence glycemia, we aim to identify the clinical and genetic predictors for glycemic progression in Chinese patients with T2D.

Methods and findings

In 1995–2007, 7,091 insulin-naïve Chinese patients (mean age 56.8 ± 13.3 [SD] years; mean age of T2D onset 51.1 ± 12.7 years; 47% men; 28.4% current or ex-smokers; median duration of diabetes 4 [IQR: 1–9] years; mean HbA1c 7.4% ± 1.7%; mean body mass index [BMI] 25.3 ± 4.0 kg/m2) were followed prospectively in the Hong Kong Diabetes Register. We examined associations of BMI and other clinical and genetic factors with glycemic progression defined as requirement of continuous insulin treatment, or 2 consecutive HbA1c ≥8.5% while on ≥2 oral glucose-lowering drugs (OGLDs), with validation in another multicenter cohort of Hong Kong Diabetes Biobank. During a median follow-up period of 8.8 (IQR: 4.8–13.3) years, incidence of glycemic progression was 48.0 (95% confidence interval [CI] 46.3–49.8) per 1,000 person-years with 2,519 patients started on insulin. Among the latter, 33.2% had a lag period of 1.3 years before insulin was initiated. Risk of progression was associated with extremes of BMI and high HbA1c. On multivariate Cox analysis, early age at diagnosis, microvascular complications, high triglyceride levels, and tobacco use were additional independent predictors for glycemic progression. A polygenic risk score (PRS) including 123 known risk variants for T2D also predicted rapid progression to insulin therapy (hazard ratio [HR]: 1.07 [95% CI 1.03–1.12] per SD; P = 0.001), with validation in the replication cohort (HR: 1.24 [95% CI 1.06–1.46] per SD; P = 0.008). A PRS using 63 BMI-related variants predicted BMI (beta [SE] = 0.312 [0.057] per SD; P = 5.84 × 10−8) but not glycemic progression (HR: 1.01 [95% CI 0.96–1.05] per SD; P = 0.747). Limitations of this study include potential misdiagnosis of T2D and lack of detailed data of drug use during follow-up in the replication cohort.

Conclusions

Our results show that approximately 5% of patients with T2D failed OGLDs annually in this clinic-based cohort. The independent associations of modifiable and genetic risk factors allow more precise identification of high-risk patients for early intensive control of multiple risk factors to prevent glycemic progression.

Klíčová slova:

Body mass index – Diabetes mellitus – HbA1c – Human genetics – Insulin – Medical risk factors – Single nucleotide polymorphisms – Type 2 diabetes


Zdroje

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