Tangjittipokin Watip, Narkdontri Tassanee, Teerawattanapong Nipaporn, Suthon Sarocha, Nakhonsri Vorthunju, Wasitthankasem Rujipat, Sudtachat Nirinya, Preechasuk Lukana, Lapinee Varisara, Thongtang Nuntakorn, Tongsima Sissades, Plengvidhya Nattachet
Department of Immunology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
Siriraj Center of Research Excellence for Diabetes and Obesity, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
Ann Med. 2025 Dec;57(1):2500697. doi: 10.1080/07853890.2025.2500697. Epub 2025 May 8.
Type 2 diabetes is a heterogeneous disease with strong genetic components. We showed earlier that newly diagnosed type 2 diabetes in Thai patients could be categorized into four clusters. This study aimed to determine the evidence of hereditary factors in these type 2 diabetes clusters.
A total of 487 subjects who were diagnosed with type 2 diabetes in two years were enrolled in the Siriraj Diabetes Center, Siriraj Hospital Bangkok, Bangkok, Thailand. They were divided into four clusters as previously described. The associations between patients' characteristics, degree of family history of diabetes (FHD), and type 2 diabetes clusters were tested using multinomial logistic regression.
Among four clusters of newly diagnosed type 2 diabetes, there were significant differences in characteristics at baseline, including age at diagnosis, BMI, waist circumference, blood sugar levels, vital signs, triglyceride, HDL, calculated LDL, creatinine and eGFR (all < .05). A relatively young age at the time of diabetes diagnosis was associated with having second-degree relatives with diabetes ( < .05) in all clusters when using mild age-related diabetes (MARD) cluster with no FHD as a control. Patients in the severe insulin-deficient diabetes (SIDD) cluster had more first-degree relatives with diabetes (odds ratio = 1.85; = .0354), while patients in the metabolic syndrome diabetes (MSD) cluster (odds ratio = 10.73; < .001) and the mild obesity-related diabetes (MOD) group (odds ratio = 6.66; = .002), had more second-degree relatives with diabetes.
Genetic factors might have various roles in the pathogenesis of type 2 diabetes, at least in newly diagnosed Thai patients. Our findings supported that genetic heterogeneity contributed to clinical heterogeneity or four different clusters. Further studies are needed in a larger sample size of these patients is needed to identify genetic loci associated with each cluster.
2型糖尿病是一种具有强大遗传成分的异质性疾病。我们之前表明,泰国患者新诊断出的2型糖尿病可分为四个聚类。本研究旨在确定这些2型糖尿病聚类中遗传因素的证据。
共有487名在两年内被诊断为2型糖尿病的受试者被纳入泰国曼谷诗里拉吉医院的诗里拉吉糖尿病中心。他们如前所述被分为四个聚类。使用多项逻辑回归检验患者特征、糖尿病家族史(FHD)程度与2型糖尿病聚类之间的关联。
在新诊断出的2型糖尿病的四个聚类中,基线特征存在显著差异,包括诊断时的年龄、体重指数、腰围、血糖水平、生命体征、甘油三酯、高密度脂蛋白、计算得出的低密度脂蛋白、肌酐和估算肾小球滤过率(均P<0.05)。当以无FHD的轻度年龄相关糖尿病(MARD)聚类作为对照时,在所有聚类中,糖尿病诊断时相对年轻的年龄与有糖尿病二级亲属相关(P<0.05)。重度胰岛素缺乏性糖尿病(SIDD)聚类中的患者有更多糖尿病一级亲属(优势比=1.85;P=0.0354),而代谢综合征糖尿病(MSD)聚类中的患者(优势比=10.73;P<0.001)和轻度肥胖相关糖尿病(MOD)组(优势比=6.66;P=0.002)有更多糖尿病二级亲属。
遗传因素可能在2型糖尿病的发病机制中起多种作用,至少在新诊断出的泰国患者中如此。我们的研究结果支持遗传异质性导致了临床异质性或四个不同的聚类。需要对这些患者进行更大样本量的进一步研究,以确定与每个聚类相关的基因位点。