Perfil de glicose em indivíduos com GCK-­MODY: monitoramento contínuo de glicose em um estudo caso controle

Abstract

Introduction: Diabetes that occurs due to a mutation in a single gene is called monogenic diabetes. Although still considered rare, it may actually be underdiagnosed or misclassified as other types of diabetes. The most frequent mutation is an inactivating one in the glucokinase (GCK) enzyme, which leads to GCK-­MODY, characterized by mild and stable fasting hyperglycemia, typically identified in young patients with a positive family history. Diagnosis is confirmed through genetic testing;; however, access remains limited and costly. Pharmacological treatment is not routinely indicated, as it is believed there is no significant risk for complications. Nevertheless, there is still a lack of data in the literature on a broader assessment of glucose profiles using continuous glucose monitoring (CGM) in patients with GCK-­MODY. CGM may provide new and previously unreported insights. Objective: To descriptively evaluate glucose behavior in patients with genetically confirmed GCK-­MODY using intermittent CGM metrics, and to compare these findings with data obtained from a control group without diabetes. Methodology: This is a cross-­sectional, observational case-­control study. Patients followed at the diabetes center of HUCFF-­UFRJ or referred from other institutions with confirmatory genetic testing for GCK-­MODY were included. Participants without diabetes were included in the control group. All participants used CGM for 14 days in a blind mode. Reports and metrics such as time in range (TIR), time above range (TAR), time below range (TBR), time in tight range (TITR), estimated average glucose, and glucose management indicator (GMI) were generated and compared between groups. Statistical analysis was performed using SPSS version 22.0, and a p-­value < 0.05 was considered statistically significant.Results: A total of 31 individuals were included: 21 in the GCK-­MODY group and 10 in the control group. In the GCK-­MODY group, all participants had a TIR > 70%, but none had a TITR > 96%, the expected level for non-­diabetic individuals, which the control group achieved. 76% (n=16) had a TITR < 90%, and of these, 31% (n=5) had a TITR < 70%. Although TIR did not differ between groups (96%± 0.55 vs. 98% ± 0.33;; p= 0.287) between groups, TITR was significantly lower in the GCK-­MODY group (78% ± 0.14 vs. 96% ± 0.33;; p< 0.001). TAR (2,6% ± 0.05 vs. 0,1% ± 0.003;; p= 0.0123), GMI (6.3 ± 0.26 vs. 5.7 ± 0.17;; p<0.001) and estimated average glucose (124.6 ± 11.26 vs. 100 ± 7.42;; p< 0.001) were higher in the GCK-­MODY group. No associations were found between specific genotypes and the magnitude of glucose profile abnormalities. Discussion and Conclusions: Despite stable glycemic patterns and adequate TIR, our findings reveal subtle and consistent glycemic abnormalities when using more sensitive parameters such as TITR. The GCK genotype did not correlate with glycemic phenotype, highlighting the importance of considering non-­genetic factors in disease expression. Larger longitudinal studies are needed to determine the clinical relevance of these findings and guide precision treatment for this population.