Background  Type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD) are often comorbid conditions, and their coexistence can exacerbate complications and damage target organs. In recent years, stem cell therapy for metabolic diseases using mesenchymal stem cell (MSC) has been emerging both domestically and internationally. However, clinical studies on their therapeutic effects are still sparse.

Objective To investigate the therapeutic potential of umbilical cord-derived mesenchymal stem cell (UC-MSC) in the amelioration of T2DM and NAFLD comorbidity.

Methods A prospective, single-center, randomized, double-blind trial was conducted in the Endocrinology Department of the First Medical Center of Chinese PLA General Hospital from October 2015 to December 2018. A total of 65 patients with T2DM and NAFLD were enrolled and assigned on a 1:1 basis to either the UC-MSC group (33 patients) or the placebo group (32 patients). Comparisons were made between pre- and post-treatment levels of blood glucose control, insulin resistance, liver ultrasound findings, degree of liver fibrosis, and selected lipid metabolism and liver function indicators.

Results In the UC-MSC group, there were 22 males and 11 females, with an average age of 51.36±8.85 years; in the placebo group, there were 22 males and 10 females, with an average age of 50.47±8.42 years. There were no statistically significant differences in gender, age, and baseline data between the two groups (P>0.05).After 9 weeks of treatment, fasting blood glucose levels in the UC-MSC group were significantly lower than baseline (7.46 ± 1.79 vs 8.33 ± 1.80, P=0.001), and they were also significantly lower than the placebo group at 9 and 20 weeks (7.46 ± 1.79 vs 8.19 ± 1.95, P=0.007; 7.51 ± 1.77 vs 9.10 ± 2.78, P=0.008). Additionally, at weeks 9, 20, and 48 of treatment, a significantly higher proportion of patients in the UC-MSC group achieved the HbA1c target (＜7.0%) compared to the placebo group (60.60% vs 28.10%, P=0.008; 51.50% vs 25.00%, P=0.028; 48.50% vs 12.50%, P=0.002). At week 20, a higher proportion of patients in the UC-MSC group showed improvement in liver ultrasound examinations compared to the placebo group (45.45% vs 18.75%, P=0.021). Hyperinsulinemic-euglycemic clamp test results indicated an increase in glucose infusion rates in the UC-MSC group at weeks 9 and 48 compared to baseline, with a significant difference from the placebo group at week 48 (4.77 ± 1.70 vs 3.57 ± 1.76, P=0.007). The UC-MSC group also showed sustained improvements over baseline levels for triglycerides (TG) and gamma-glutamyl transferase (GGT), a significant reduction in total cholesterol (TC) at weeks 9 and 48, and a significant decrease in alanine transaminase (ALT) at week 20, while aspartate transaminase (AST) levels showed no significant change at any time points.

Conclusion UC-MSC therapy can improve glycemic control to some extent, enhance hepatic structure and function, boost insulin sensitivity, and modulate lipid metabolism in patients with concurrent T2DM and NAFLD.