Decreased Serum Dickkopf-1 Levels After Hypoglycemic Therapy in Patients with Type 2 Diabetes Mellitus

Abstract

Aim

Dickkopf-1 (DKK-1) is a major inhibitor of Wingless protein signaling pathway, which is involved in glucose metabolism and cardiovascular diseases. The aim of the study was to investigate the changes of serum DKK-1 levels after hypoglycemic treatments and the relationship between DKK-1 and clinical parameters.

Materials and Methods

The study was a sub-study of a previously published clinical trial (the effect of Acarbose on glycemic variability in patients with type 2 diabetes mellitus using premixed insulin compared to metformin). All subjects underwent anthropometric and biochemical assessments at baseline and endpoint. Serum DKK-1 levels of 92 subjects were measured at baseline and after 12-week hypoglycemic treatment.

Results

DKK-1 levels were significantly decreased after hypoglycemic treatment for 12 weeks (P < 0.001). ΔDKK-1 levels were not correlated with improvement of metabolic parameters (all P > 0.05) but were negatively correlated with baseline DKK-1 levels (r = −0.263, P = 0.011). Spearman correlation showed that baseline DKK-1 levels were positively related to baseline total cholesterol (r = 0.226, P = 0.030) and low-density lipoprotein cholesterol (LDL-C) (r = 0.277, P = 0.007). Compared with the higher baseline DKK-1 group (≥3700 pg/mL), subjects in the lower baseline DKK-1 group (<3700 pg/mL) had significantly lower baseline glycated hemoglobin A1c levels (P = 0.008) and LDL-C levels (P = 0.048). Systolic and diastolic pressure were decreased more significantly in the lower baseline DKK-1 group than that in the higher baseline DKK-1 group (both P < 0.05).

Conclusion

Serum DKK-1 levels were decreased after hypoglycemic treatments. Patients with lower baseline DKK-1 levels were featured by more favorable cardiometabolic factors.

Keywords:

• cardiovascular risk factor
• dickkopf-1
• hypoglycemic treatment
• type 2 diabetes mellitus

Abbreviations

BMI, body mass index; DBP, diastolic pressure; DKK-1, Dickkopf-1; FPG, fasting plasma glucose; HbA1c, glycated hemoglobin A1c; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; PG2h, 2-hour postprandial plasma glucose; SBP, systolic pressure; TC, total cholesterol; TG, triglycerides.

Data Sharing Statement

The data that support the findings of this study are available upon reasonable request from the corresponding authors (Jingyi Lu, [email protected]; Xiaojing Ma, [email protected]).

Ethical Approval and Informed Consent

The study was approved by the Ethics Committee of Shanghai Jiao Tong University Affiliated Sixth People’s Hospital and was in accordance with the principle of the 1964 Helsinki Declaration. Informed consent was obtained from all individual participants included in the study.

Acknowledgments

We would like to thank all the involved clinicians, nurses, and technicians for their contribution to the study. We are grateful to all the participants for their dedication in data collection and laboratory measurements.

Disclosure

The authors report no conflicts of interest in this work.

Additional information

Funding

This work was funded by the Shanghai Municipal Commission of Health and Family planning General Program (201840232).