Effects of Insulin and Oral Antidiabetic Agents on Glucose Metabolism, Vascular Dysfunction and Skeletal Muscle Inflammation in Type 2 Diabetic Subjects

Authors

J. Joya-Galeana
M. Fernandez
A. Cervera
Sara M. Reyna, The University of Texas Rio Grande ValleyFollow
S. Ghosh
C. Triplitt
N. Musi
Ralph A. DeFronzo
Eugenio Cersosimo

Document Type

Article

Publication Date

5-2011

Abstract

Background

To test potential differences between the actions of anti-diabetic medications, we examined the effects of oral hypoglycemic agents versus insulin glargine-apidra therapy in T2DM.

Methods

T2DM subjects were randomized to either OHA (pioglitazone, metformin, glipizide, n=9) or IT (n=12) for 6 months. Carotid intimal media thickness (CIMT), vascular reactivity [FMD] (% change in brachial arterial diameter [BD] post-ischemia), and sublingual nitrate [SLN] were measured with ultrasonography. Euglycemic hyperinsulinemic (80 mU/m2) clamp with [3]-3H-glucose and muscle biopsies were performed.

Results

FPG (∼257 to ∼124, OHA ∼256 to ∼142 mg/dl, IT) and HgbA1C (∼10.3 to ∼6.4%, OHA; ∼10.7 to ∼7.1%, IT), improved comparably. EGP (∼2.1 to ∼1.7, OHA; ∼2.3 to ∼2.0, IT) and EGP suppression by insulin (∼0.4 to ∼0.3, OHA; ∼0.5 to ∼0.7 mg/kg.min, IT) was different. Total glucose disposal [TGD/I) × 100] increased in OHA (∼5.2 to ∼8.1, p=0.03), but not in IT (∼6.0 to ∼5.4 mg/kg.min/μU/ml × 100). OHA reduced CIMT (∼0.080 to ∼0.068, p<0.05), whereas IT did not (∼0.075 to ∼0.072 cm). After SLN, BD increased in OHA (∼8.7 to ∼18.2%), but not in IT (∼11.2 to ∼15.0), [p<0.02]. Except for plasma adiponectin (∼7 to ∼15, OHA vs. ∼6 to ∼10, IT), changes in inflammatory markers in the circulation and in muscle (IκBα, SOD2 & MCP1, p-ERK and JNK) were equivalent.

Conclusions

OHA and IT achieved adequate glycemic control and the effects on circulating and muscle inflammatory biomarkers were similar, but only OHA improved insulin sensitivity, vascular function and CIMT. These findings in a small sample suggest that the use of OHA provide additional benefits to patients with T2DM.

Comments

PMC Copyright notice

Recommended Citation

Joya-Galeana, J., Fernandez, M., Cervera, A., Reyna, S., Ghosh, S., Triplitt, C., Musi, N., DeFronzo, R. A., & Cersosimo, E. (2011). Effects of insulin and oral anti-diabetic agents on glucose metabolism, vascular dysfunction and skeletal muscle inflammation in type 2 diabetic subjects. Diabetes/metabolism research and reviews, 27(4), 373–382. https://doi.org/10.1002/dmrr.1185

Publication Title

Diabetes/metabolism research and reviews

DOI

10.1002/dmrr.1185

Academic Level

faculty

Mentor/PI Department

Office of Human Genetics