Creatine Phosphokinase Level Accompanied with Macro-Creatine Phosphokinase Type 1 Negatively Correlates with Plasma Glucose Control in a Patient with Type 2 Diabetes Mellitus

Introduction: The macromolecular complex formed by creatine phosphokinase (CPK) is most probably an immune complex. Most of the macro-CPK migrates between CPK-MM and CPK-MB, exhibiting an atypical band on isozyme electrophoresis. Either IgA or IgG has been identified with its CPK link (termed as macro-CPK type 1). However, the biological and pathological significance of these complexes found in patients with wide-ranging disease states remains unclear. Herein, we first report a case of type 2 diabetes mellitus associated with hypercreatinekinasemia caused by macro-CPK type 1, with CPK levels negatively correlated with blood glucose control. Case Presentation: A 53-year-old Japanese woman with no complaints of muscle weakness, myalgia, and numbness of the extremities was diagnosed with hypercreatinekinasemia. Over the past years, she received empagliflozin, mitiglinide, voglibose, vildagliptin, metformin, methyl thiazide, and ezetimibe. Serum biochemistry revealed elevated CPK levels. The highest CPK value was 1,063 U/L, and the three major isozymes CPK-BB, CPK-MB, and CPK-MM accounted for 0%, 2%, and 98%, respectively. Notably, CPK isozyme electrophoresis performed on a cellulose acetate membrane detected an additional band that migrated between the CPK-MB and CPK-MM bands, suggesting macro-CPK type 1, which occupied 82% of the total CPK. The densitometric profile of the electrophoresis pattern revealed that CPK-BB, CPK-MB, and CPK-MM constituted 0%, 2%, and 16%, respectively. Moreover, serum CPK levels combined with macro-CPK showed a significant negative correlation with the HbA1c values (r = −0.498, p < 0.001). Conclusions: Serum CPK levels accompanied with macro-CPK type 1 negatively correlate with plasma glucose control. Although the pathophysiological role of macro-CPK remains unclear, our case report may provide a new viewpoint regarding macro-CPK etiology.