A Comparison of Daily Glucose Fluctuation Between GCK-MODY and Type 2 Diabetes Using Continuous Glucose Monitoring Technology. Diabetes 2023;72:812–818

I recently read the article by Ren et al. (1) and think it is valuable work but could have gone further in investigating glucokinase variant-induced maturity-onset diabetes of the young (GCK-MODY). The authors are to be commended for their use of a cross-sectional case-control study design to compare glucose control for participants with GCK-MODY, type 2 diabetes, and normal glucose tolerance (25 participants per group) using masked glucose readings and encouraging others to further this work. The authors showed that GCK-MODY and type 2 diabetes could be differentiated on the basis of glucose control during the day, but not the night, and that glucose measures of SD of blood glucose, mean amplitude of glycemic excursions, mean of daily difference, and largest amplitude of glycemic excursions were higher for those with GCK-MODY than for subjects with normal glucose tolerance.

Time in range (3.9–10.0 mmol/L glucose) was used to compare the three groups. While fine from a numerical point of view, both Guenat et al. (2) and Chakera et al. (3) report that the counterregulatory response for those with GCK-MODY occurs at higher glucose levels than for the other groups. This shift to higher levels is seen in the minimum of glucose (MIN) values of Table 1 in the article by Ren et al., with the mean MIN for subjects with GCK-MODY, subjects with type 2 diabetes, and control subjects 4.2, 2.90, and 2.5 mmol/L, respectively. Hence, an additional analysis with consideration of this shift could have been completed. Even within the given range, the authors show that there are some incidences of hypoglycemia in those with GCK-MODY. Chakera et al. (3) indicate an exaggerated response for counterregulatory hormones for those with GCK-MODY in comparisons with subjects with type 2 diabetes and control subjects, although baseline levels were similar. This leads to the question as to whether those with GCK-MODY who had incidences of hypoglycemia had symptoms. Please note that the authors do not detail whether those with GCK-MODY came to their clinic for incidental causes or were symptomatic.

In the article by Ren et al. there appear to be bimodal distributions for GCK-MODY in scatterplots for SD of blood glucose (Supplementary Fig. 3B), mean amplitude of glycemic excursions (Supplementary Fig. 3C), and mean of daily difference (Supplementary Fig. 3D). This is reminiscent of a small study on serum levels of pancreatic stone protein, where there also appeared to be a bimodal distribution for those with GCK-MODY (4). While these results could be related to the small sample sizes, one cannot dismiss that the data indicate the possibility of two basic GCK-MODY phenotypes, one more common and one less common. Once again, it would be interesting to know whether all of the participants with GCK-MODY were asymptomatic. Further research in this area is needed. Finally, Nomura et al. (5) have published a case study showing flash glucose monitoring results for a child with GCK-MODY that fits well with this study and may interest the authors. I look forward to reading about more work from this group or from others that builds on this study.