Evaluation of myokine profile in patients with diabetic ketoacidosis

The effects of myokines mainly released from the muscle tissue on glucose and lipid metabolism are still under investigation, and their roles in the pathogenesis of diabetic ketoacidosis (DKA) are yet unknown. In this study, our aim was to investigate the serum levels and changes of myokines (irisin, myonectin, interleukin-6 [IL-6], angiogenin, osteoprotegerin, fibroblast growth factor-21 [FGF- 21]) during diabetic ketoacidosis (DKA) and after DKA resolution. We included 27 patients with DKA (15 female [56%] /12 male [44%]) and 45 healthy volunteers (25 female [56%] /20 male [44%]) in control group (p=1). In the patient group, the median (IQR) value for age was 32 (23-47) years, while in the control group, the median (IQR) value for age was 30 (29-49) years (p=0.47). In the patient group, the median (IQR) value for body mass index (BMI) was 23 (19.8-27.6) kg/m2, while in the control group the median (IQR) value for BMI was 23.6 (19.5-25.9) kg/m2 (p=0.61). The patient and control groups were matched in terms of fat mass, fat percentage, muscle mass, and muscle percentage (p=0.14 for fat mass, p=0.33 for fat percentage, p=0.71 for muscle mass, p=0.34 for muscle percentage). Serum irisin levels during DKA were found to be lower compared to irisin levels after DKA resolution (Irisin level ng/mL, mean [±standard deviation], during DKA: 1328 [±736], after DKA resolution: 1946 [±996], p=0.013). Analysis of other myokines showed no statistically significant differences between levels measured during DKA and after DKA resolution (Myonectin level ng/mL, median [IQR], during DKA: 0.043 [0.03-0.07], after DKA resolution: 0.040 [0.03-0.06], p=0.20; IL-6 level pg/mL, median [IQR], during DKA: 2.03 [1.30-3.38], after DKA resolution: 1.64 [1.48-2], p=0.14; angiogenin level ng/mL, median [IQR], during DKA: 571 [494-970], after DKA resolution: 867 [569-1387], p=0.16; osteoprotegerin level ng/mL, median [IQR], during DKA: 0.92 [0.67-1.68], after DKA resolution: 0.78 [0.66-1.35], p=0.25; FGF-21 level pg/mL, mean [±standard deviation], during DKA: 2.41 [±1.33], after DKA resolution: 1.97 [±1.26], p=0.12). Correlation analysis was conducted between myokine and glucagon levels during DKA and after DKA resolution and age, duration of diabetes, glucose, HbA1c, anion gap levels, and results of body composition analysis. During DKA, significant correlations were observed between irisin and age (r= -0.394, p=0.04), irisin and BMI (r=0.49, p=0.02), myonectin and HbA1c (r= -0.50, p=0.01), FGF-21 and HbA1c (r= -0.38, p=0.005), IL-6 and HbA1c (r= -0.57, p=0.002), osteoprotegerin and anion gap (r=0.401, p=0.04), osteoprotegerin and alkaline phosphatase (r=0.565, p=0.003), glucagon and glucose (r=0.43, p=0.026), glucagon and anion gap (r=0.41, p=0.03), angiogenin and muscle mass (r=0.58, p=0.007). In terms of myokine levels during DKA, significant correlations were detected between irisin and IL-6 (r=0.66, p<0.001), myonectin and IL-6 (r=0.40, p=0.004), myonectin and FGF-21 (r=0.60, p=0.003), IL-6 and FGF-21 (r=0.54, p=0.005), and angiogenin and osteoprotegerin (r=0.45, p=0.02). Based on the data from this study, it can be concluded that muscle tissue might be involved in the process of DKA by the help of irisin and that bone tissue could have a buffering role during ketoacidosis.