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Combination peroxisome proliferator-activated receptor gamma and alpha agonist treatment in Type 2 diabetes prevents the beneficial pioglitazone effect on liver fat content.
Diabet Med. 2010 Feb; 27(2):150-6.DM

Abstract

AIMS

Peroxisome proliferator-activated receptor (PPAR)-gamma and PPAR-alpha agonists individually reduce intra-organ triglyceride content and improve insulin sensitivity. However, the precise effects of combined PPAR-gamma and PPAR-alpha therapy on intra-organ triglyceride content and insulin sensitivity in subjects with Type 2 diabetes have not yet been determined.

METHODS

Diet-controlled Type 2 subjects (n = 9) were studied before and after 16 weeks of combined PPAR-gamma [pioglitazone (PIO), 45 mg daily] and PPAR-alpha [bezafibrate (BEZA), modified release 400 mg daily] agonist therapy. Glucose metabolism and endogenous glucose production were measured following a standard liquid test meal. Liver and muscle triglyceride levels were measured by (1)H magnetic resonance spectroscopy.

RESULTS

Combined PIO and BEZA therapy reduced mean fasting (7.5 +/- 0.5 vs. 6.5 +/- 0.2 mmol/l, P = 0.04) and peak postprandial plasma glucose (15.3 +/- 1.1 vs. 11.7 +/- 0.6 mmol/l, P = 0.007). No significant change in hepatic or muscle triglyceride content was observed. Postprandial suppression of endogenous glucose production remained similar on both study days. Both subcutaneous and visceral fat content increased following therapy.

CONCLUSIONS

Combined PIO and BEZA therapy in Type 2 diabetes does not decrease intrahepatic triglyceride content or postprandial endogenous glucose production. This study demonstrates an unexpected adverse interaction of PPAR-alpha with PPAR-gamma agonist therapy.

Authors+Show Affiliations

Newcastle Magnetic Resonance Centre, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20546257

Citation

Balasubramanian, R, et al. "Combination Peroxisome Proliferator-activated Receptor Gamma and Alpha Agonist Treatment in Type 2 Diabetes Prevents the Beneficial Pioglitazone Effect On Liver Fat Content." Diabetic Medicine : a Journal of the British Diabetic Association, vol. 27, no. 2, 2010, pp. 150-6.
Balasubramanian R, Gerrard J, Dalla Man C, et al. Combination peroxisome proliferator-activated receptor gamma and alpha agonist treatment in Type 2 diabetes prevents the beneficial pioglitazone effect on liver fat content. Diabet Med. 2010;27(2):150-6.
Balasubramanian, R., Gerrard, J., Dalla Man, C., Firbank, M. J., Lane, A., English, P. T., Cobelli, C., & Taylor, R. (2010). Combination peroxisome proliferator-activated receptor gamma and alpha agonist treatment in Type 2 diabetes prevents the beneficial pioglitazone effect on liver fat content. Diabetic Medicine : a Journal of the British Diabetic Association, 27(2), 150-6. https://doi.org/10.1111/j.1464-5491.2009.02906.x
Balasubramanian R, et al. Combination Peroxisome Proliferator-activated Receptor Gamma and Alpha Agonist Treatment in Type 2 Diabetes Prevents the Beneficial Pioglitazone Effect On Liver Fat Content. Diabet Med. 2010;27(2):150-6. PubMed PMID: 20546257.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Combination peroxisome proliferator-activated receptor gamma and alpha agonist treatment in Type 2 diabetes prevents the beneficial pioglitazone effect on liver fat content. AU - Balasubramanian,R, AU - Gerrard,J, AU - Dalla Man,C, AU - Firbank,M J, AU - Lane,A, AU - English,P T, AU - Cobelli,C, AU - Taylor,R, PY - 2010/6/16/entrez PY - 2010/6/16/pubmed PY - 2010/10/19/medline SP - 150 EP - 6 JF - Diabetic medicine : a journal of the British Diabetic Association JO - Diabet. Med. VL - 27 IS - 2 N2 - AIMS: Peroxisome proliferator-activated receptor (PPAR)-gamma and PPAR-alpha agonists individually reduce intra-organ triglyceride content and improve insulin sensitivity. However, the precise effects of combined PPAR-gamma and PPAR-alpha therapy on intra-organ triglyceride content and insulin sensitivity in subjects with Type 2 diabetes have not yet been determined. METHODS: Diet-controlled Type 2 subjects (n = 9) were studied before and after 16 weeks of combined PPAR-gamma [pioglitazone (PIO), 45 mg daily] and PPAR-alpha [bezafibrate (BEZA), modified release 400 mg daily] agonist therapy. Glucose metabolism and endogenous glucose production were measured following a standard liquid test meal. Liver and muscle triglyceride levels were measured by (1)H magnetic resonance spectroscopy. RESULTS: Combined PIO and BEZA therapy reduced mean fasting (7.5 +/- 0.5 vs. 6.5 +/- 0.2 mmol/l, P = 0.04) and peak postprandial plasma glucose (15.3 +/- 1.1 vs. 11.7 +/- 0.6 mmol/l, P = 0.007). No significant change in hepatic or muscle triglyceride content was observed. Postprandial suppression of endogenous glucose production remained similar on both study days. Both subcutaneous and visceral fat content increased following therapy. CONCLUSIONS: Combined PIO and BEZA therapy in Type 2 diabetes does not decrease intrahepatic triglyceride content or postprandial endogenous glucose production. This study demonstrates an unexpected adverse interaction of PPAR-alpha with PPAR-gamma agonist therapy. SN - 1464-5491 UR - https://www.unboundmedicine.com/medline/citation/20546257/Combination_peroxisome_proliferator_activated_receptor_gamma_and_alpha_agonist_treatment_in_Type_2_diabetes_prevents_the_beneficial_pioglitazone_effect_on_liver_fat_content_ L2 - https://doi.org/10.1111/j.1464-5491.2009.02906.x DB - PRIME DP - Unbound Medicine ER -