Abstract:
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.
journal_name
PLoS Medjournal_title
PLoS medicineauthors
Jiang G,Luk AO,Tam CHT,Lau ES,Ozaki R,Chow EYK,Kong APS,Lim CKP,Lee KF,Siu SC,Hui G,Tsang CC,Lau KP,Leung JYY,Tsang MW,Kam G,Lau IT,Li JK,Yeung VT,Lau E,Lo S,Fung SKS,Cheng YL,Chow CC,Pearson ER,So WY,doi
10.1371/journal.pmed.1003209subject
Has Abstractpub_date
2020-07-28 00:00:00pages
e1003209issue
7eissn
1549-1277issn
1549-1676pii
PMEDICINE-D-20-00322journal_volume
17pub_type
杂志文章相关文献
PLOS MEDICINE文献大全abstract:BACKGROUND:Stillbirth is strongly related to impaired fetal growth. However, the relationship between fetal growth and stillbirth is difficult to determine because of uncertainty in the timing of death and confounding characteristics affecting normal fetal growth. METHODS AND FINDINGS:We conducted a population-based c...
journal_title:PLoS medicine
pub_type: 杂志文章
doi:10.1371/journal.pmed.1001633
更新日期:2014-04-22 00:00:00
abstract::Is it ethical for scientists to conduct or to benefit from research in another country if that research would be unlawful, or not generally accepted, in their own country? ...
journal_title:PLoS medicine
pub_type: 杂志文章
doi:10.1371/journal.pmed.0040010
更新日期:2007-02-01 00:00:00
abstract:BACKGROUND TO THE DEBATE:The tobacco control community is divided on whether or not to inform the public that using oral, smokeless tobacco (Swedish snus) is less hazardous to health than smoking tobacco. Proponents of "harm reduction" point to the Swedish experience. Snus seems to be widely used as an alternative to c...
journal_title:PLoS medicine
pub_type: 杂志文章
doi:10.1371/journal.pmed.0040185
更新日期:2007-07-01 00:00:00
abstract:BACKGROUND:Introduction of pneumococcal conjugate vaccines (PCVs) of limited valency is justified in Africa by the high burden of pneumococcal disease. Long-term beneficial effects of PCVs may be countered by serotype replacement. We aimed to determine the impact of PCV-7 vaccination on pneumococcal carriage in rural G...
journal_title:PLoS medicine
pub_type: 杂志文章,随机对照试验
doi:10.1371/journal.pmed.1001107
更新日期:2011-10-01 00:00:00
abstract:BACKGROUND:Prescription opioid misuse has become a leading cause of unintentional injury and death among adolescents and young adults in the United States. However, there is limited information on how adolescents and young adults obtain prescription opioids. There are also inadequate recent data on the prevalence of ad...
journal_title:PLoS medicine
pub_type: 杂志文章
doi:10.1371/journal.pmed.1002922
更新日期:2019-11-05 00:00:00
abstract::Systematic reviews and meta-analyses are essential to summarize evidence relating to efficacy and safety of health care interventions accurately and reliably. The clarity and transparency of these reports, however, is not optimal. Poor reporting of systematic reviews diminishes their value to clinicians, policy makers...
journal_title:PLoS medicine
pub_type: 共识发展会议,指南,杂志文章
doi:10.1371/journal.pmed.1000100
更新日期:2009-07-21 00:00:00
abstract::In a Perspective, David Peiris and Dorairaj Prabhakaran discuss implications and challenges of cardiovascular disease risk assessments in the population of India. ...
journal_title:PLoS medicine
pub_type: 评论,杂志文章
doi:10.1371/journal.pmed.1002582
更新日期:2018-06-19 00:00:00
abstract:BACKGROUND:Historically, the main focus of studies of childhood mortality has been the infant and under-five mortality rates. Neonatal mortality (deaths <28 days of age) has received limited attention, although such deaths account for about 41% of all child deaths. To better assess progress, we developed annual estimat...
journal_title:PLoS medicine
pub_type: 杂志文章
doi:10.1371/journal.pmed.1001080
更新日期:2011-08-01 00:00:00
abstract:BACKGROUND:Care advances in the United States (US) have led to improved survival of children with neurological impairment (NI). Children with NI may account for an increasing proportion of hospital resources. However, this assumption has not been tested at a national level. METHODS AND FINDINGS:We conducted a study of...
journal_title:PLoS medicine
pub_type: 杂志文章
doi:10.1371/journal.pmed.1001158
更新日期:2012-01-01 00:00:00
abstract::[This corrects the article DOI: 10.1371/journal.pmed.1001895.]. ...
journal_title:PLoS medicine
pub_type: 已发布勘误
doi:10.1371/journal.pmed.1002065
更新日期:2016-06-10 00:00:00
abstract:BACKGROUND:The risk of perinatal death and severe neonatal morbidity increases gradually after 41 weeks of pregnancy. Several randomised controlled trials (RCTs) have assessed if induction of labour (IOL) in uncomplicated pregnancies at 41 weeks will improve perinatal outcomes. We performed an individual participant da...
journal_title:PLoS medicine
pub_type: 杂志文章,meta分析
doi:10.1371/journal.pmed.1003436
更新日期:2020-12-08 00:00:00
abstract:BACKGROUND:Envenoming resulting from snakebites is an important public health problem in many tropical and subtropical countries. Few attempts have been made to quantify the burden, and recent estimates all suffer from the lack of an objective and reproducible methodology. In an attempt to provide an accurate, up-to-da...
journal_title:PLoS medicine
pub_type: 杂志文章
doi:10.1371/journal.pmed.0050218
更新日期:2008-11-04 00:00:00
abstract:BACKGROUND:Although gastric cancer has declined dramatically in the US, the disease remains the second leading cause of cancer mortality worldwide. A better understanding of reasons for the decline can provide important insights into effective preventive strategies. We sought to estimate the contribution of risk factor...
journal_title:PLoS medicine
pub_type: 杂志文章
doi:10.1371/journal.pmed.1001451
更新日期:2013-01-01 00:00:00
abstract:BACKGROUND:Research needs to be reported transparently so readers can critically assess the strengths and weaknesses of the design, conduct, and analysis of studies. Reporting guidelines have been developed to inform reporting for a variety of study designs. The objective of this study was to identify whether there is ...
journal_title:PLoS medicine
pub_type: 杂志文章
doi:10.1371/journal.pmed.1001069
更新日期:2010-08-01 00:00:00
abstract:BACKGROUND:Effective strategies are needed for the prevention of mother-to-child HIV transmission (PMTCT) in resource-limited settings. The Kisumu Breastfeeding Study was a single-arm open label trial conducted between July 2003 and February 2009. The overall aim was to investigate whether a maternal triple-antiretrovi...
journal_title:PLoS medicine
pub_type: 临床试验,杂志文章
doi:10.1371/journal.pmed.1001015
更新日期:2011-03-01 00:00:00
abstract:BACKGROUND:Antenatal corticosteroid therapy (ACT) is used clinically to prepare the fetal lung for impending preterm birth, but animal and human studies link corticosteroids to smaller birth size. Whether ACT is associated with birth size is debated; therefore, we assessed differences in birth size in treated versus un...
journal_title:PLoS medicine
pub_type: 杂志文章
doi:10.1371/journal.pmed.1002746
更新日期:2019-02-26 00:00:00
abstract::In a Policy Forum, Peter Hotez and colleagues discuss vaccination exemptions in US states and possible consequences for infectious disease outbreaks. ...
journal_title:PLoS medicine
pub_type: 杂志文章
doi:10.1371/journal.pmed.1002578
更新日期:2018-06-12 00:00:00
abstract:BACKGROUND:The relationship between population trends in delaying childbirth and rising rates of primary cesarean delivery is unclear. The aims of the present study were (1) to characterize the association between maternal age and the outcome of labor, (2) to determine the proportion of the increase in primary cesarean...
journal_title:PLoS medicine
pub_type: 杂志文章
doi:10.1371/journal.pmed.0050144
更新日期:2008-07-01 00:00:00
abstract::In a Perspective, Lynn Morris and Nonhlanhla Mkhize discuss the prospects for broadly neutralizing antibodies to be used in preventing HIV infection. ...
journal_title:PLoS medicine
pub_type: 杂志文章,评审
doi:10.1371/journal.pmed.1002436
更新日期:2017-11-14 00:00:00
abstract:BACKGROUND:Tobacco addiction is a complex, multicomponent phenomenon stemming from nicotine's pharmacology and the user's biology, psychology, sociology, and environment. After decades of public denial, the tobacco industry now agrees with public health authorities that nicotine is addictive. In 2000, Philip Morris bec...
journal_title:PLoS medicine
pub_type: 历史文章,杂志文章
doi:10.1371/journal.pmed.1002562
更新日期:2018-05-01 00:00:00
abstract:BACKGROUND:Meta-analyses of antidepressant medications have reported only modest benefits over placebo treatment, and when unpublished trial data are included, the benefit falls below accepted criteria for clinical significance. Yet, the efficacy of the antidepressants may also depend on the severity of initial depress...
journal_title:PLoS medicine
pub_type: 杂志文章,meta分析
doi:10.1371/journal.pmed.0050045
更新日期:2008-02-01 00:00:00
abstract:BACKGROUND:Increased adiposity is linked with higher risk for cardiometabolic diseases. We aimed to determine to what extent elevated body mass index (BMI) within the normal weight range has causal effects on the detailed systemic metabolite profile in early adulthood. METHODS AND FINDINGS:We used Mendelian randomizat...
journal_title:PLoS medicine
pub_type: 杂志文章
doi:10.1371/journal.pmed.1001765
更新日期:2014-12-09 00:00:00
abstract:BACKGROUND:Plasmodium falciparum merozoite surface protein 3 is a malaria vaccine candidate that was identified, characterised, and developed based on a unique immuno-clinical approach. The vaccine construct was derived from regions fully conserved among various strains and containing B cell epitopes targeted by human ...
journal_title:PLoS medicine
pub_type: 临床试验,杂志文章
doi:10.1371/journal.pmed.0020344
更新日期:2005-11-01 00:00:00
abstract::Andrew Seale and colleagues discuss the development of a global strategy to counter sexually transmitted infections. ...
journal_title:PLoS medicine
pub_type: 杂志文章
doi:10.1371/journal.pmed.1002330
更新日期:2017-06-27 00:00:00
abstract:BACKGROUND:The response to the next influenza pandemic will likely include extensive use of antiviral drugs (mainly oseltamivir), combined with other transmission-reducing measures. Animal and in vitro studies suggest that some strains of influenza may become resistant to oseltamivir while maintaining infectiousness (f...
journal_title:PLoS medicine
pub_type: 杂志文章
doi:10.1371/journal.pmed.0040015
更新日期:2007-01-01 00:00:00
abstract::Chris Beyrer and colleagues reflect on an underappreciated trend in multiple African, Asian, and Caribbean settings, in which the provision of HIV and other essential health services for sexual and gender minorities is expanding despite challenging legal and social environments. ...
journal_title:PLoS medicine
pub_type: 社论
doi:10.1371/journal.pmed.1002154
更新日期:2016-10-25 00:00:00
abstract:BACKGROUND:Skin atrophy is a common manifestation of aging and is frequently accompanied by ulceration and delayed wound healing. With an increasingly aging patient population, management of skin atrophy is becoming a major challenge in the clinic, particularly in light of the fact that there are no effective therapeut...
journal_title:PLoS medicine
pub_type: 杂志文章
doi:10.1371/journal.pmed.0030493
更新日期:2006-12-01 00:00:00
abstract::Substantial progress has been made towards the goal of ending the HIV/AIDS epidemic due to advancements in both prevention and treatment of HIV. However, major challenges still remain. We describe basic principles of epidemic control in the context of HIV and identify a number of attainable goals in terms of control a...
journal_title:PLoS medicine
pub_type: 杂志文章
doi:10.1371/journal.pmed.1002729
更新日期:2019-01-18 00:00:00
abstract::In this month's editorial, the PLOS Medicine Editors discuss the role of preprints in human health research and propose a 3-part framework for ensuring benefit. ...
journal_title:PLoS medicine
pub_type: 评论,社论
doi:10.1371/journal.pmed.1002563
更新日期:2018-04-16 00:00:00
abstract:BACKGROUND TO THE DEBATE:Umbilical cord blood--the blood that remains in the placenta after birth--can be collected and stored frozen for years. A well-accepted use of cord blood is as an alternative to bone marrow as a source of hematopoietic stem cells for allogeneic transplantation to siblings or to unrelated recipi...
journal_title:PLoS medicine
pub_type: 杂志文章
doi:10.1371/journal.pmed.0020044
更新日期:2005-02-01 00:00:00