title: Lifestyle and metformin treatment favorably influence lipoprotein subfraction distribution in the Diabetes Prevention Program.
abstract: BACKGROUND
  Although intensive lifestyle change (ILS) and metformin reduce diabetes incidence in subjects with impaired glucose tolerance (IGT), their effects on lipoprotein subfractions have not been studied.
  
  
  OBJECTIVE
  The objective of the study was to characterize the effects of ILS and metformin vs placebo interventions on lipoprotein subfractions in the Diabetes Prevention Program.
  
  
  METHODS
  This was a randomized clinical trial, testing the effects of ILS, metformin, and placebo on diabetes development in subjects with IGT.
  
  
  METHODS
  Selected individuals with IGT randomized in the Diabetes Prevention Program participated in the study.
  
  
  METHODS
  Interventions included randomization to metformin 850 mg or placebo twice daily or ILS aimed at a 7% weight loss using a low-fat diet with increased physical activity.
  
  
  METHODS
  Lipoprotein subfraction size, density, and concentration measured by magnetic resonance and density gradient ultracentrifugation at baseline and 1 year were measured.
  
  
  RESULTS
  ILS decreased large and buoyant very low-density lipoprotein, small and dense low-density lipoprotein (LDL), and small high-density lipoprotein (HDL) and raised large HDL. Metformin modestly reduced small and dense LDL and raised small and large HDL. Change in insulin resistance largely accounted for the intervention-associated decreases in large very low-density lipoprotein, whereas changes in body mass index (BMI) and adiponectin were strongly associated with changes in LDL. Baseline and a change in adiponectin were related to change in large HDL, and BMI change associated with small HDL change. The effect of metformin to increase small HDL was independent of adiponectin, BMI, and insulin resistance.
  
  
  CONCLUSIONS
  ILS and metformin treatment have favorable effects on lipoprotein subfractions that are primarily mediated by intervention-related changes in insulin resistance, BMI, and adiponectin. Interventions that slow the development of diabetes may also retard the progression of atherosclerosis.
authors: MD, c/o The Diabetes Prevention Program Coordinating Center, Biostatistics Center, George Washington University, 6110 Executive Boulevard, Suite 750, Rockville, Maryland 20852. dppmail@biostat.bsc.gwu.edu.
authors: R
authors: R
authors: Goldberg
authors: M
authors: M
authors: Temprosa
authors: J
authors: J
authors: Otvos
authors: J
authors: J
authors: Brunzell
authors: S
authors: S
authors: Marcovina
authors: K
authors: K
authors: Mather
authors: R
authors: R
authors: Arakaki
authors: K
authors: K
authors: Watson
authors: E
authors: E
authors: Horton
authors: E
authors: E
authors: Barrett-Connor
mesh_terms: D000328:Adult; D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy / Q000517:prevention & control*; D018752:Diet, Fat-Restricted; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008019:Life Style; D008074:Lipoproteins / Q000097:blood*; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D040242:Risk Reduction Behavior; D016896:Treatment Outcome
chemical_list: D007004:Hypoglycemic Agents; D008074:Lipoproteins; D008687:Metformin
references: J Investig Med. 2007 May;55(4):187-94
references: 17651673
references: Biochim Biophys Acta. 2012 Mar;1821(3):365-72
references: 21986251
references: Diabetes. 2003 Feb;52(2):453-62
references: 12540621
references: Circulation. 2011 May 24;123(20):2292-333
references: 21502576
references: Circulation. 2006 Mar 28;113(12):1556-63
references: 16534013
references: Curr Opin Lipidol. 2006 Aug;17(4):412-7
references: 16832165
references: J Clin Endocrinol Metab. 2004 Jun;89(6):2601-7
references: 15181030
references: N Engl J Med. 2002 Nov 7;347(19):1483-92
references: 12421890
references: Diabetes Care. 2006 Sep;29(9):2102-7
references: 16936160
references: Endocrinology. 2011 Jan;152(1):247-54
references: 21147877
references: Diabetes Care. 2005 Apr;28(4):888-94
references: 15793191
references: Diabetes Care. 2009 Jul;32(7):1317-9
references: 19389813
references: Med Sci Sports Exerc. 1997 Jun;29(6 Suppl):S1-205
references: 9243481
references: Clin Chem. 2011 Mar;57(3):392-410
references: 21266551
references: Obesity (Silver Spring). 2009 Sep;17(9):1768-75
references: 19498345
references: Diabetes. 1995 Oct;44(10):1218-26
references: 7556961
references: J Clin Lipidol. 2007 Dec;1(6):583-92
references: 19657464
references: Lancet. 2009 Nov 14;374(9702):1677-86
references: 19878986
references: Arteriosclerosis. 1985 Mar-Apr;5(2):162-8
references: 3977776
references: Clin Chem. 1992 Sep;38(9):1632-8
references: 1326420
references: Clin Chim Acta. 2006 Sep;371(1-2):163-8
references: 16712824
references: N Engl J Med. 2002 Feb 7;346(6):393-403
references: 11832527
references: J Lipid Res. 1989 Aug;30(8):1117-26
references: 2504859
references: Obes Surg. 2009 Jul;19(7):894-904
references: 18972174
references: Clin Lab Med. 2006 Dec;26(4):847-70
references: 17110242
references: Diabetes. 2007 Apr;56(4):1153-9
references: 17395752
references: Diabetologia. 1985 Jul;28(7):412-9
references: 3899825
references: Ann Epidemiol. 1999 Jul;9(5):314-24
references: 10976858
references: Diabetes. 2008 Apr;57(4):980-6
references: 18192541
references: Metabolism. 1999 Jul;48(7):822-6
references: 10421219
references: J Lipid Res. 2010 Aug;51(8):2405-12
references: 20631298
references: Arterioscler Thromb Vasc Biol. 2008 Jul;28(7):1225-36
references: 18565848