CAMKK1 in Obesity and Type 2 Diabetes Mellitus: Evidence of Interaction With Appetite‐Regulating, Metabolic and Inflammatory Factors

Introduction Calcium/calmodulin‐dependent protein kinase kinase 1 (CAMKK1) regulates energy homeostasis through AMP‐activated protein kinase (AMPK). CAMKK1 has been implicated in appetite and satiety regulation; however, its role in obesity or type 2 diabetes mellitus (T2DM) remains unexplored. In this cross‐sectional study, the primary aim was to confirm whether CAMKK1 is elevated in individuals with diabetes. The secondary aim was to investigate CAMKK1's molecular correlates. Methods CAMKK1 serum levels in individuals with obesity ( n = 3,061), patients with T2DM ( n = 4,910) and controls ( n = 44,257) were retrieved and compared (age, body mass index—BMI and sex‐adjusted ANCOVA). Pearson correlation coefficients and linear regression coefficients (age and BMI‐adjusted) were computed. The moderation effect of diagnostic groups was also assessed. The interaction between factors was explored by mixed graphical models. Results CAMKK1 was elevated in patients with T2DM, in comparison to both individuals with obesity and controls (post hoc comparison, Tukey‐adjusted p = 0.010 and p = 0.044, respectively). Across diagnostic groups, positive associations were observed between CAMKK1 and AMPK (min β > 0.400, max p < 0.001) or TNFα (min > β 0.070, max p < 0.001). A positive association with leptin ( β = 0.010, p = 0.002) and ghrelin ( β = 0.005, p = 0.048) was observed only within controls. Multivariate multivariable models confirmed that specific interactions between factors were disrupted in patients with T2DM ( p < 0.001). Conclusion These findings provide new insights into the role of CAMKK1 in obesity and T2DM. Future research may further explore CAMKK1's interplay with inflammatory pathways.