Different accelerators to early-onset Type 2 diabetes: a comparison of Anglo-Celtic and Chinese patients
ABSTRACT The "accelerator hypothesis" postulates that metabolic syndrome (MS) factors-overweight and insulin resistance-increase functional demand on islets, accelerating diabetes onset to a younger age in both Type 1 and Type 2 diabetes (T2DM). Previous research has focused only on the former. We examine to what extent the MS and individual components are accelerators to the earlier onset of T2DM in Anglo-Celtic and Chinese populations.
A cross-sectional study of 1016 Anglo-Celtic and 1514 Chinese patients with recent-onset diabetes (duration <2 years) evaluated over a 12-year period. The MS syndrome and components were analyzed after stratification by age at presentation.
The Anglo-Celtic group shows a high prevalence of MS in early-onset disease and a striking inverse relationship of body mass index (BMI) with age at presentation. For every increase in BMI of 1 kg/m(2), there is a reduction in the age of presentation by 0.5 years (r=-0.3; P<.0001) .Younger groups had a higher prevalence of insulin resistance, elevated triglyceride (Tg), and low high-density lipoprotein cholesterol (HDL-C) (P<.0001 for trend for all three indices). In contrast, the Chinese group showed no relationship between age of presentation with BMI, insulin resistance, Tg, or HDL-C.
MS factors are important accelerators for T2DM in the Anglo-Celtic but not the Chinese population. This suggests that earlier onset of pancreatic beta cell deficiency is more important as an accelerator of diabetes presentation in Chinese. These data confirm the heterogeneity of T2DM and support the need for more ethnic specific strategies in diabetes prevention.
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ABSTRACT: To identify novel type 2 diabetes gene variants and confirm previously identified ones, a three-staged genome-wide association study was performed in the Japanese population. In the stage 1 scan, we genotyped 519 case and 503 control subjects with 482,625 single nucleotide polymorphism (SNP) markers; in the stage 2 panel comprising 1,110 case subjects and 1,014 control subjects, we assessed 1,456 SNPs (P < 0.0025, stage 1); additionally to direct genotyping, 964 healthy control subjects formed the in silico control panel. Along with genome-wide exploration, we aimed to replicate the disease association of 17 SNPs from 16 candidate loci previously identified in Europeans. The associated and/or replicated loci (23 SNPs; P < 7 x 10(-5) for genome-wide exploration and P < 0.05 for replication) were examined in the stage 3 panel comprising 4,000 case subjects and 12,569 population-based samples, from which 4,889 nondiabetic control subjects were preselected. The 12,569 subjects were used for overall risk assessment in the general population. Four loci-1 novel with suggestive evidence (PEPD on 19q13, P = 1.4 x 10(-5)) and three previously reported-were identified; the association of CDKAL1, CDKN2A/CDKN2B, and KCNQ1 were confirmed (P < 10(-19)). Moreover, significant associations were replicated in five other candidate loci: TCF7L2, IGF2BP2, SLC30A8, HHEX, and KCNJ11. There was substantial overlap of type 2 diabetes susceptibility genes between the two populations, whereas effect size and explained variance tended to be higher in the Japanese population. The strength of association was more prominent in the Japanese population than in Europeans for more than half of the confirmed type 2 diabetes loci.Diabetes 04/2009; 58(7):1690-9. DOI:10.2337/db08-1494 · 8.47 Impact Factor