世衛：成人罹患糖尿病 30年來增加3倍 【大紀元2016年04月06日訊】世界衛生組織（WHO）4月6日首度發布糖尿病全球報告顯示，估計罹患糖尿病的成人人數到2014年激增至4.22億人，增幅幾乎是1980年的3倍。此外，臺灣團隊近年首度研究發現亞洲人不胖也會罹患糖尿病的主因。 世衛說：「2014年全球估計有4.22億成人患有糖尿病，相較之下，1980年為1.08億人。」據中央社報導，世衛報告指出，糖尿病2012年直接造成150萬人死亡，而同年，與糖尿病有關的高血糖還另造成220萬人死亡。糖尿病有2種類型。目前沒有已知辦法可避免第1型糖尿病，此型病人胰臟製造的胰島素不足。大多數糖尿病人罹患的是第2型，與肥胖和其他生活型態因素有關，發生在成年人，而患此型糖尿病的孩童也越來越多。世衛說，要減少糖尿病帶來加劇的負擔，需大刀闊斧改變全球「飲食和運動習慣」，尤其在生命早期關鍵行為模式形成時。法新社報導，世衛警告說，糖尿病大幅擴散，主要因為全世界發生「飲食、行動和生活方式」改變。
亞洲人糖尿病主因 臺灣團隊發現 有別西方國家，有7成亞洲人不胖也得糖尿病，國家衛生研究院和臺中榮民總醫院長許惠恒3月18日公布最新研究發現，若負責調控基酶的DNA開關故障，使原具保護作用的細胞發炎，誘發糖尿病。相關研究已發表在國際知名期刊《自然》（Nature）及《腫瘤標靶》（Oncotarget）。過去研究指出，「肥胖」是第2型糖尿病主要致病因子，北美地區糖尿病患者有8成為肥胖者、歐洲地區5成，但亞洲地區病患僅2至3成為肥胖者，顯示東方人罹患第2型糖尿病主因可能非肥胖。糖尿病15年來高居臺灣人10大死因前5名，2014年光是糖尿病及其併發症的健保支出就多達新臺幣410億元，且臺灣近9成民眾罹患第2型糖尿病。國家衛生研究院臺中榮民總醫院耗時4、5年，研究逾百名糖尿病患者，發現若體內調控「MAP4K4激酶」的DNA故障，原本具有保護功效的「T淋巴細胞」就會過度活化，分泌大量發炎性細胞，誘發胰島素作用細胞產生胰島素組抗，血糖持續上升，引發第2型糖尿病。「MAP4K4激酶」就如同汽車的煞車系統，若煞車系統中的某零件故障，就會導致汽車無法正常煞車，因此第2型糖尿病患者即便非肥胖，也有罹患糖尿病可能。臺中榮民總醫院長、中華民國糖尿病學會理事長許惠恒指出，這項研究是臺灣領先全球的新發現，如開啟一扇非肥胖糖尿病研究的大門，未來或許可偵測細胞發炎，及早介入透過運動、控制飲食等，減少糖尿病發生。責任編輯：鍾元
Epigenetic regulation of HGK/MAP4K4 in T cells of type 2 diabetes patients. Oncotarget. 2016 Feb 24. Type 2 diabetes (T2D) is a complex and heterogeneous disease. Obesity increases the risk of obese T2D; but in Asia non-obese T2D is prevalent. The cause of non-obese T2D has remained elusive. We studied the potential involvement of HGK/MAP4K4 in T2D using clinical samples from newly diagnosed, drug-naïve patients and healthy controls. HGK levels fell and IL-6 levels increased in T cells from T2D patients. Frequencies of IL-6-producing T cells were correlated with glucose levels after glucose-tolerance tests (but not body mass index and waist circumference) and inversely correlated with HGK expression levels. Moreover, methylation frequencies of the HGK promoter were increased in T2D patients and correlated with glucose levels after glucose-tolerance tests. The correlation was independent of body mass index. Demethylation treatment increased HGK expression levels and reduced IL-6 production in T2D T cells. This report identifies HGK methylation/down regulation in T cells as a potential biomarker for non-obese T2D.
One of the major risk factors for type 2 diabetes (T2D) is obesity. However, not all obese individuals develop diabetes, and not all T2D patients are obese (body mass index (BMI) greater than 30) [1]. According to WHO criteria for body obesity (BMI ≥ 30), non-obese T2D comprises about 80% of T2D cases in Asia, 55% of those in Europe, and 20% of those in North America and Australia [1-3]. In addition, based on WHO Expert Consultation in 2002 and epidemiological studies in Asia [4], the BMI criteria in Asia are adjusted lower (normal, overweight, and obese are BMI < 23, 23 ≤ BMI < 27.5, and BMI ≥ 27.5, respectively). Although the cut-off values for obesity are decreased, there are still many non-obese patients with T2D in Asia: about 70% of the total T2D in that continent [5, 6]. Dysregulation of the immune system plays a pivotal role in the pathogenesis of T2D [7]. Besides an increase in macrophages, an increase in CD8+ T cells or Th1 cells in adipose tissues contributes to T2D development in high-fat diet HFD-fed mice [8, 9]. Studying immunometabolism might help develop treatment for and prevention of T2D. HPK1/GCK-like kinase (HGK/MAP4K4) is a member of MAP kinase kinase kinase kinases (MAP4Ks), which belong to the Ste20-like serine/threonine kinase family [10, 11]. The involvement of HGK in macrophage TNF-α signaling and adipocyte insulin resistance has been reported in studies using siRNA knockdown and overexpression systems [12, 13]. In the genotyping for tagging single nucleotide polymorphisms (SNPs) of 1769 DNA samples from the peripheral blood of prediabetic Europeans [14], two SNPs in the HGK locus were found to be associated with increased glucose levels in patients, while two other HGK SNPs were associated with reduced insulin release only in lean subjects (BMI < 25) [14]. Paradoxically, a fifth SNP and one of the latter two HGK SNPs are associated with enhanced plasma IL-6 but not with TNF-α levels [14]. Thus, the relative contribution of HGK expression to the pathophysiology of T2D may be mediated by cells other than macrophages. To date, the roles of two other MAP4Ks, HPK1 (MAP4K1) and GLK (MAP4K3), in T-cell signaling and T-cell-mediated immune responses have been demonstrated [15, 16]. Recently, we studied the in vivo role of HGK in immune responses by generating T-cell-specific HGK conditional knockout (T-HGK cKO) mice; we found that these mice displayed higher serum IL-6 levels and spontaneously developed insulin resistance without large weight gain [17]. Thus, we hypothesized that the loss of HGK expression in T cells and the increase of IL-6-producing T cells are associated with human T2D.
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