Institute of Endocrinology, Lithuanian University of Health Sciences, Kaunas, Lithuania.
Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania.
Pediatr Diabetes. 2022 Nov;23(7):1009-1016. doi: 10.1111/pedi.13404. Epub 2022 Sep 6.
The aims were (1) to assess beta-cell function in GCK diabetes patients over 2-year period; (2) to evaluate the dynamics of beta-cell function in HNF1A and KCNJ11 patients after treatment optimization; using mixed meal tolerance test (MMTT) as a gold standard for non-invasive beta-cell function assessment.
Twenty-two GCK diabetes patients, 22 healthy subjects, 4 patients with HNF1A and 2 with KCNJ11 were recruited. Firstly, beta-cell function was compared between GCK patients versus controls; the dynamics of beta-cell function were assessed in GCK patients with two MMTTs in 2-year period. Secondly, the change of beta-cell function was evaluated in HNF1A and KCNJ11 patients after successful treatment optimization in 2-year period.
GCK diabetes patients had lower area under the curve (AUC) of C-peptide (CP), average CP and peak CP compared to controls. Also, higher levels of fasting, average, peak and AUC of glycemia during MMTT were found in GCK patients compared to healthy controls. No significant changes in either CP or glycemia dynamics were observed in GCK diabetes group comparing 1st and 2nd MMTTs. Patients with HNF1A and KCNJ11 diabetes had significantly improved diabetes control 2 years after the treatment was optimized (HbA1c 7.1% vs. 5.9% [54 mmol/mol vs. 41 mmol/mol], respectively, p = 0.028). Higher peak CP and lower HbA1c were found during 2nd MMTT in patients with targeted treatment compared to the 1st MMTT before the treatment change.
In short-term perspective, GCK diabetes group revealed no deterioration of beta-cell function. Individualized treatment in monogenic diabetes showed improved beta-cell function.
（1）在 2 年期间评估 GCK 糖尿病患者的β细胞功能；（2）使用混合餐耐量试验（MMTT）作为评估非侵入性β细胞功能的金标准，评估 HNF1A 和 KCNJ11 患者在治疗优化后的β细胞功能变化。
招募了 22 名 GCK 糖尿病患者、22 名健康受试者、4 名 HNF1A 患者和 2 名 KCNJ11 患者。首先，将 GCK 患者与对照组进行比较，评估β细胞功能；在 2 年期间对 GCK 患者进行两次 MMTT 以评估β细胞功能的动态变化。其次，在 2 年期间成功治疗优化后，评估 HNF1A 和 KCNJ11 患者β细胞功能的变化。
与对照组相比，GCK 糖尿病患者的 C 肽（CP）曲线下面积（AUC）、平均 CP 和峰值 CP 均较低。此外，GCK 患者在 MMTT 期间的空腹、平均、峰值和 AUC 血糖水平也高于健康对照组。与第一次 MMTT 相比，GCK 糖尿病组在比较两次 MMTT 时，CP 或血糖动力学均无明显变化。HNF1A 和 KCNJ11 糖尿病患者在治疗优化后 2 年时，糖尿病控制明显改善（HbA1c 分别为 7.1%和 5.9%[54mmol/mol 和 41mmol/mol]，p=0.028）。与治疗前的第一次 MMTT 相比，靶向治疗患者在第二次 MMTT 时的峰值 CP 更高，HbA1c 更低。
从短期来看，GCK 糖尿病组的β细胞功能没有恶化。单基因糖尿病的个体化治疗显示出改善的β细胞功能。
