Abstract：
OBJECTIVE: Asians have a high prevalence of young-onset diabetes, but the pattern of monogenic diabetes is unknown. We aimed to determine the prevalence of monogenic diabetes in Chinese patients with young-onset diabetes and compare the clinical characteristics and outcome between patients with and without monogenic diabetes.
METHODS: We sequenced a targeted panel of 33 genes related to monogenic diabetes in 1021 Chinese patients with non-type 1 diabetes diagnosed at age ≤40 years. Incident complications including cardiovascular disease (CVD), end-stage kidney disease (ESKD) and all-cause death were captured since enrolment (1995-2012) until 2019.
RESULTS: In this cohort (mean ± SD age at diagnosis: 33.0 ± 6.0 years, median[IQR] diabetes duration 7.0[1.0-15.0] years at baseline, 44.9% men), 22(2.2%, 95% confidence interval[CI] 1.4%-3.2%) had monogenic diabetes. Pathogenic (P) or likely pathogenic (LP) variants were detected in GCK (n = 6), HNF1A (n = 9), HNF4A (n = 1), PLIN1 (n = 1) and PPARG (n = 2), together with copy number variations in HNF1B (n = 3). Over a median follow-up of 17.1 years, 5(22.7%) patients with monogenic diabetes (incidence rate 12.3[95% CI 5.1-29.4] per 1000 person-years) versus 254(25.4%) without monogenic diabetes (incidence rate 16.7[95% CI 14.8-18.9] per 1000 person-years) developed the composite outcome of CVD, ESKD and/or death (p = 0.490). The multivariable Cox model did not show any difference in hazards for composite events between groups.
CONCLUSIONS: In Chinese with young-onset non-type 1 diabetes, at least 2% of cases were contributed by monogenic diabetes, over 80% of which were accounted for by P/LP variants in common MODY genes. The incidence of diabetes complications was similar between patients with and without monogenic diabetes.
METHODS: We sequenced a targeted panel of 33 genes related to monogenic diabetes in 1021 Chinese patients with non-type 1 diabetes diagnosed at age ≤40 years. Incident complications including cardiovascular disease (CVD), end-stage kidney disease (ESKD) and all-cause death were captured since enrolment (1995-2012) until 2019.
RESULTS: In this cohort (mean ± SD age at diagnosis: 33.0 ± 6.0 years, median[IQR] diabetes duration 7.0[1.0-15.0] years at baseline, 44.9% men), 22(2.2%, 95% confidence interval[CI] 1.4%-3.2%) had monogenic diabetes. Pathogenic (P) or likely pathogenic (LP) variants were detected in GCK (n = 6), HNF1A (n = 9), HNF4A (n = 1), PLIN1 (n = 1) and PPARG (n = 2), together with copy number variations in HNF1B (n = 3). Over a median follow-up of 17.1 years, 5(22.7%) patients with monogenic diabetes (incidence rate 12.3[95% CI 5.1-29.4] per 1000 person-years) versus 254(25.4%) without monogenic diabetes (incidence rate 16.7[95% CI 14.8-18.9] per 1000 person-years) developed the composite outcome of CVD, ESKD and/or death (p = 0.490). The multivariable Cox model did not show any difference in hazards for composite events between groups.
CONCLUSIONS: In Chinese with young-onset non-type 1 diabetes, at least 2% of cases were contributed by monogenic diabetes, over 80% of which were accounted for by P/LP variants in common MODY genes. The incidence of diabetes complications was similar between patients with and without monogenic diabetes.
摘要：
目的：亚洲人年轻发病的糖尿病患病率很高，但是单基因糖尿病的模式是未知的。我们旨在确定中国年轻发病的糖尿病患者中单基因糖尿病的患病率，并比较有和没有单基因糖尿病的患者的临床特征和预后。
方法：我们在1021名年龄≤40岁的中国非1型糖尿病患者中对33个与单基因糖尿病相关的基因进行了测序。意外并发症，包括心血管疾病（CVD），从入组(1995-2012年)到2019年都有终末期肾病(ESKD)和全因死亡病例.
结果：在该队列中（诊断时的平均±SD年龄：33.0±6.0岁，基线时糖尿病病程中位数[IQR]7.0[1.0-15.0]年，44.9%男性)，22（2.2%，95%置信区间[CI]1.4%-3.2%)患有单基因糖尿病。在GCK中检测到致病性（P）或可能的致病性（LP）变异（n=6），HNF1A（n=9），HNF4A（n=1），PLIN1（n=1）和PPARG（n=2），以及HNF1B的拷贝数变异(n=3)。平均随访17.1年，5例(22.7%)单基因型糖尿病患者(发病率12.3[95%CI5.1-29.4]/1000人年)与254例(25.4%)无单基因型糖尿病患者(发病率16.7[95%CI14.8-18.9]/1000人年)发生了CVD的复合结局,ESKD和/或死亡(p=0.490)。多变量Cox模型未显示组间复合事件的风险差异。
结论：在中国年轻发病的非1型糖尿病患者中，至少2%的病例由单基因糖尿病引起，其中80%以上由常见MODY基因中的P/LP变异所占。有和没有单基因糖尿病的患者之间糖尿病并发症的发生率相似。
方法：我们在1021名年龄≤40岁的中国非1型糖尿病患者中对33个与单基因糖尿病相关的基因进行了测序。意外并发症，包括心血管疾病（CVD），从入组(1995-2012年)到2019年都有终末期肾病(ESKD)和全因死亡病例.
结果：在该队列中（诊断时的平均±SD年龄：33.0±6.0岁，基线时糖尿病病程中位数[IQR]7.0[1.0-15.0]年，44.9%男性)，22（2.2%，95%置信区间[CI]1.4%-3.2%)患有单基因糖尿病。在GCK中检测到致病性（P）或可能的致病性（LP）变异（n=6），HNF1A（n=9），HNF4A（n=1），PLIN1（n=1）和PPARG（n=2），以及HNF1B的拷贝数变异(n=3)。平均随访17.1年，5例(22.7%)单基因型糖尿病患者(发病率12.3[95%CI5.1-29.4]/1000人年)与254例(25.4%)无单基因型糖尿病患者(发病率16.7[95%CI14.8-18.9]/1000人年)发生了CVD的复合结局,ESKD和/或死亡(p=0.490)。多变量Cox模型未显示组间复合事件的风险差异。
结论：在中国年轻发病的非1型糖尿病患者中，至少2%的病例由单基因糖尿病引起，其中80%以上由常见MODY基因中的P/LP变异所占。有和没有单基因糖尿病的患者之间糖尿病并发症的发生率相似。
