The high incidence of heart failure in patients with type 2 diabetes mellitus (T2DM) can be attributed to myocardial fibrosis, weakening of ventricular function, and damage to myocardial muscles, such as mitochondrial dysfunction. We studied physiological changes in the heart, which are early characteristics of diabetic myocardial disease, using 6- and 8-week old obese T2DM model mice (db/db, BKS.Cg-Dock7m+/+Leprdb/J) and wild type mice. We confirmed mitochondrial dysfunction in 8 weeks old db/db mice, which was not accompanied by any changes in heart function. Metabolomic analysis performed on heart tissues revealed that the levels of 12 metabolites changed substantially. The levels of glucose and leucine increased considerably, and lipid metabolites changed. Protein expression analysis of the blood and heart tissues confirmed a remarkable increase in cereblon (CRBN) levels and a decrease in AMP-activated protein kinase, a negative regulator. Furthermore, in silico studies on data in the blood of diabetic cardiomyopathy (DCM) patients. These results show that an increase in CRBN, without any abnormal heart function, in early T2DM mice roles an important role in the reduction of mitochondrial function and metabolomic changes. Therefore, CRBN level in blood and heart tissues may serve as a diagnostic biomarker for the detection of early DCM.