Familial Early-Onset Type 2 Diabetes in Chinese Patients

Ng, Maggie; Lee, Shaochin; Ko, Gary T.C.; Li, June K.Y.; So, Wing‐Yee; Hashim, Y; Barnett, Anthony; Mackay, Ian R.; Critchley, J. A. J. H.; Cockram, Clive S.; Chan, Juliana C.N.

doi:10.2337/diacare.24.4.663

Cited by 75 publications

(48 citation statements)

References 42 publications

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“…The inclusion of young diabetic patients with familial history may increase genetic loading of the study population. Despite our previous findings suggesting up to 14% presence of monogenic diabetes in the young patients (20), 50% of these young patients were obese, mimicking the predominant feature of type 2 diabetes. The control subjects consisted of 1,530 subjects with normal glucose tolerance (fasting plasma glucose [FPG] Ͻ6.1 mmol/l).…”

mentioning

confidence: 58%

Implication of Genetic Variants Near TCF7L2, SLC30A8, HHEX, CDKAL1, CDKN2A/B, IGF2BP2, and FTO in Type 2 Diabetes and Obesity in 6,719 Asians

et al. 2008

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OBJECTIVE— Recent genome-wide association studies have identified six novel genes for type 2 diabetes and obesity and confirmed TCF7L2 as the major type 2 diabetes gene to date in Europeans. However, the implications of these genes in Asians are unclear. RESEARCH DESIGN AND METHODS— We studied 13 associated single nucleotide polymorphisms from these genes in 3,041 patients with type 2 diabetes and 3,678 control subjects of Asian ancestry from Hong Kong and Korea. RESULTS— We confirmed the associations of TCF7L2 , SLC30A8 , HHEX , CDKAL1 , CDKN2A / CDKN2B , IGF2BP2 , and FTO with risk for type 2 diabetes, with odds ratios ranging from 1.13 to 1.35 (1.3 × 10 −12 < P unadjusted < 0.016). In addition, the A allele of rs8050136 at FTO was associated with increased BMI in the control subjects ( P unadjusted = 0.008). However, we did not observe significant association of any genetic variants with surrogate measures of insulin secretion or insulin sensitivity indexes in a subset of 2,662 control subjects. Compared with subjects carrying zero, one, or two risk alleles, each additional risk allele was associated with 17% increased risk, and there was an up to 3.3-fold increased risk for type 2 diabetes in those carrying eight or more risk alleles. Despite most of the effect sizes being similar between Asians and Europeans in the meta-analyses, the ethnic differences in risk allele frequencies in most of these genes lead to variable attributable risks in these two populations. CONCLUSIONS— Our findings support the important but differential contribution of these genetic variants to type 2 diabetes and obesity in Asians compared with Europeans.

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confidence: 58%

Implication of Genetic Variants Near TCF7L2, SLC30A8, HHEX, CDKAL1, CDKN2A/B, IGF2BP2, and FTO in Type 2 Diabetes and Obesity in 6,719 Asians

et al. 2008

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“…In a cross-sectional survey, 23% of young diabetic patients attending a hospital clinic in Hong Kong had albuminuria and 14% had retinopathy, despite a relatively short duration of disease of less than 5 years [30,47]. This early evidence of nephropathy was often unaccompanied by clinical evidence of retinopathy.…”

Section: High Prevalence Of Microvascular Complicationsmentioning

confidence: 98%

“…Approximately 50% of young Chinese diabetic patients were obese with multiple cardiovascular risk factors such as dyslipidemia, hypertension, and albuminuria, suggesting early onset of the metabolic syndrome [19,30]. In the Hong Kong Diabetes Family Study, nearly 50% of siblings of young diabetic patients had glucose intolerance.…”

Section: Early Onset Of Metabolic Syndromementioning

confidence: 99%

“…More than 80% of Caucasian patients with maturity-onset diabetes of the young (MODY) were accounted by mutations in the two common MODY genes, including glucokinase and hepatocyte nuclear factor (HNF)-1α, as well as other less common MODY genes (HNF-4α, HNF-1β, and insulin promoter factor-1) [28••]. In Chinese, mutations in MODY genes were present in more than 10% of young patients with familial diabetes [29][30][31][32]. Other genetic variants that have been reported in Chinese include mitochondrial DNA A3243G mutations [33][34][35] and amylin S20G mutations [36], with a prevalence of less than 1% to 2% increasing to more than 3% in those with positive family history, young onset of disease, or insulin deficiency.…”

Section: Monogenic Forms Of Diabetesmentioning

confidence: 99%

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Lessons learned from young-onset diabetes in China

Chan

Ng²

2003

Curr Diab Rep

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The prevalence of young-onset diabetes is rapidly rising in China. Young-onset diabetes is etiologically and phenotypically heterogeneous. Thirty percent to 50% of these patients have insulin secretory failure owing to autoimmune or monogenic or other yet to be identified forms of diabetes. Others have a strong family history of diabetes and exhibit features of the metabolic syndrome. Management of these young patients poses major diagnostic and therapeutic challenges, which require a multidisciplinary and holistic approach to ensure that these subjects are identified early and managed appropriately. Understanding the molecular basis of diabetes in these subjects may also eventually lead to improvement in diagnosis, classification, and treatment.

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“…Subsequently, families without any GIT or diabetic members remaining were excluded. In addition, 48 of the probands with positive family history had participated in a previous study to screen for mutations in the MODY2 and MODY3 genes and in the mitochondrial DNA nucleotide 3243 A3 G mutation (19). Families with these gene mutations were also excluded.…”

Section: Methodsmentioning

confidence: 99%