PMID- 26978661
OWN - NLM
STAT- MEDLINE
DCOM- 20160726
LR  - 20221207
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 11
IP  - 3
DP  - 2016
TI  - The Role of Metformin Response in Lipid Metabolism in Patients with Recent-Onset 
      Type 2 Diabetes: HbA1c Level as a Criterion for Designating Patients as 
      Responders or Nonresponders to Metformin.
PG  - e0151543
LID - 10.1371/journal.pone.0151543 [doi]
LID - e0151543
AB  - BACKGROUND: In this study, we investigated whether response to metformin, the 
      most frequently drug for diabetes treatment, influences the therapeutic effects 
      of antilipidemic medication in newly diagnosed patients with type 2 diabetes 
      mellitus (T2DM). METHODS: A total of 150 patients with T2DM were classified into 
      two groups following 3 months of metformin therapy (1000 mg twice daily): 
      responders (patients showing >/=1% reduction in HbA1c from baseline) and 
      nonresponders (patients showing <1% reduction in HbA1c from baseline). The 
      patients received atorvastatin 20 mg, gemfibrozil 300 mg, or atorvastatin 20 mg 
      and gemfibrozil 300 mg daily. PRINCIPAL FINDINGS: HbA1c and fasting glucose 
      levels were significantly different between baseline and 3 months among 
      responders receiving atorvastatin; however, these differences were not 
      statistically significant in nonresponders. Atherogenic ratios of low-density 
      lipoprotein cholesterol to high-density lipoprotein cholesterol (LDL-C/HDL-C; p = 
      0.002), total cholesterol to HDL-C (TC/HDL-C; p<0.001) and AIP (the atherogenic 
      index of plasma; p = 0.004) decreased significantly in responders receiving 
      atorvastatin than in nonresponders. Moreover, responders receiving atorvastatin 
      showed a significant increase in HDL-C levels but nonresponders receiving 
      atorvastatin did not (p = 0.007). The multivariate model identified a significant 
      association between metformin response (as the independent variable) and TG, TC, 
      HDL-C and LDL-C (dependent variables; Wilk's lambda = 0.927, p = 0.036). CONCLUSIONS: 
      Metformin response affects therapeutic outcomes of atorvastatin on atherogenic 
      lipid markers in patients newly diagnosed with T2DM. Metformin has a greater 
      impact on BMI in responders of metformin compared to nonresponders. Adoption of 
      better therapeutic strategies for reducing atherogenic lipid markers may be 
      necessary for metformin nonresponders.
FAU - Kashi, Zahra
AU  - Kashi Z
AD  - Diabetes Research Center, Imam Teaching Hospital, Mazandaran University of 
      Medical Sciences, Sari, Iran.
FAU - Mahrooz, Abdolkarim
AU  - Mahrooz A
AD  - Immunogenetic Research Center, Mazandaran University of Medical Sciences, Sari, 
      Iran.
AD  - Department of Clinical Biochemistry and Genetics, Faculty of Medicine, Mazandaran 
      University of Medical Sciences, Sari, Iran.
FAU - Kianmehr, Anvarsadat
AU  - Kianmehr A
AD  - Biochemistry and Metabolic Disorders Research Center, Golestan University of 
      Medical Sciences, Gorgan, Iran.
AD  - Department of Medical Biotechnology, School of Advanced Technologies in Medicine, 
      Golestan University of Medical Sciences, Gorgan, Iran.
FAU - Alizadeh, Ahad
AU  - Alizadeh A
AD  - Department of Epidemiology and Reproductive Health, Reproductive Epidemiology 
      Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, 
      Iran.
LA  - eng
PT  - Journal Article
PT  - Observational Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20160315
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Blood Glucose)
RN  - 0 (Cholesterol, HDL)
RN  - 0 (Cholesterol, LDL)
RN  - 0 (Glycated Hemoglobin A)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Hypolipidemic Agents)
RN  - 9100L32L2N (Metformin)
RN  - A0JWA85V8F (Atorvastatin)
RN  - Q8X02027X3 (Gemfibrozil)
SB  - IM
MH  - Adult
MH  - Atorvastatin/pharmacokinetics/*pharmacology/therapeutic use
MH  - Biological Transport/drug effects
MH  - Blood Glucose/analysis
MH  - Blood Pressure/drug effects
MH  - Body Mass Index
MH  - Cholesterol, HDL/blood
MH  - Cholesterol, LDL/blood
MH  - Diabetes Mellitus, Type 2/blood/complications/*drug therapy
MH  - Drug Monitoring
MH  - Drug Resistance
MH  - Drug Synergism
MH  - Drug Therapy, Combination
MH  - Dyslipidemias/blood/*drug therapy/etiology
MH  - Female
MH  - Gemfibrozil/*pharmacology/therapeutic use
MH  - Glycated Hemoglobin/*analysis
MH  - Humans
MH  - Hypoglycemic Agents/*pharmacology/therapeutic use
MH  - Hypolipidemic Agents/*pharmacology/therapeutic use
MH  - Male
MH  - Metformin/*pharmacology/therapeutic use
MH  - Middle Aged
PMC - PMC4792461
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2016/03/16 06:00
MHDA- 2016/07/28 06:00
PMCR- 2016/03/15
CRDT- 2016/03/16 06:00
PHST- 2015/09/26 00:00 [received]
PHST- 2016/02/29 00:00 [accepted]
PHST- 2016/03/16 06:00 [entrez]
PHST- 2016/03/16 06:00 [pubmed]
PHST- 2016/07/28 06:00 [medline]
PHST- 2016/03/15 00:00 [pmc-release]
AID - PONE-D-15-42061 [pii]
AID - 10.1371/journal.pone.0151543 [doi]
PST - epublish
SO  - PLoS One. 2016 Mar 15;11(3):e0151543. doi: 10.1371/journal.pone.0151543. 
      eCollection 2016.