PMID- 27347563 OWN - NLM STAT- MEDLINE DCOM- 20180423 LR - 20220310 IS - 2380-6591 (Electronic) IS - 2380-6583 (Print) VI - 1 IP - 2 DP - 2016 May 1 TI - Association of Lipoproteins, Insulin Resistance, and Rosuvastatin With Incident Type 2 Diabetes Mellitus : Secondary Analysis of a Randomized Clinical Trial. PG - 136-45 LID - 10.1001/jamacardio.2016.0096 [doi] AB - IMPORTANCE: Statins decrease levels of low-density lipoprotein (LDL) and triglycerides as well as cardiovascular events but increase the risk for a diagnosis of type 2 diabetes mellitus (T2DM). The risk factors associated with incident T2DM are incompletely characterized. OBJECTIVE: To investigate the association of lipoprotein subclasses and size and a novel lipoprotein insulin resistance (LPIR) score (a composite of 6 lipoprotein measures) with incident T2DM among individuals randomized to a high-intensity statin or placebo. DESIGN, SETTING, AND PARTICIPANTS: This secondary analysis of the JUPITER trial (a placebo-controlled randomized clinical trial) was conducted at 1315 sites in 26 countries and enrolled 17 802 men 50 years or older and women 60 years or older with LDL cholesterol levels less than 130 mg/dL, high-sensitivity C-reactive protein levels of at least 2 mg/L, and triglyceride levels less than 500 mg/dL. Those with T2DM were excluded. A prespecified secondary aim was to assess the effect of rosuvastatin calcium on T2DM. Incident T2DM was monitored for a median of 2.0 years. Data were collected from February 4, 2003, to August 20, 2008, and analyzed (intention-to-treat) from December 1, 2013, to January 21, 2016. INTERVENTIONS: Rosuvastatin calcium, 20 mg/d, or placebo. MAIN OUTCOMES AND MEASURES: Size and concentration of lipids, apolipoproteins, and lipoproteins at baseline (11 918 patients with evaluable plasma samples) and 12 months after randomization (9180 patients). The LPIR score, a correlate of insulin resistance, was calculated as a weighted combination of size and concentrations of LDL, very low-density lipoprotein (VLDL), and high-density lipoprotein (HDL) particles. RESULTS: Among the 11 918 patients (4334 women [36.4%]; median [interquartile range] age, 66 [60-71] years), rosuvastatin lowered the levels of LDL particles (-39.6%; 95% CI, -49.4% to -24.6%), VLDL particles (-19.6%; 95% CI, -40.6% to 10.3%), and VLDL triglycerides (-15.2%; 95% CI, -35.9% to 11.3%) and shifted the lipoprotein subclass distribution toward smaller LDL size (-1.5%; 95% CI, -3.7% to 0.5%), larger VLDL size (2.8%; 95% CI, -5.8% to 12.7%), and lower LPIR score (-3.2%; 95% CI, -20.6% to 16.9%). In analyses adjusted for age, sex, race or ethnic origin, exercise, educational level, family history, and smoking, the hazard ratio (HR) for T2DM per SD of LPIR score in the placebo arm was 1.99 (95% CI, 1.64-2.42); in the rosuvastatin arm, 2.06 (95% CI, 1.74-2.43). After additional adjustment for systolic blood pressure, body mass index, high-sensitivity C-reactive protein, hemoglobin A1c, HDL cholesterol, LDL cholesterol, and triglycerides, the LPIR score remained associated with T2DM in the placebo arm (HR, 1.35; 95% CI, 1.03-1.76) and rosuvastatin arm (HR, 1.60; 95% CI, 1.27-2.03). Similar trends were seen at 12 months. The LPIR score improved the model likelihood ratio (chi2 = 18.23; P < .001) and categorical net reclassification index (0.039; 95% CI, 0.003-0.072). CONCLUSIONS AND RELEVANCE: In apparently healthy people, LPIR score was positively associated with incident T2DM, including during rosuvastatin therapy. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00239681. FAU - Dugani, Sagar B AU - Dugani SB AD - Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts2Division of Internal Medicine, St Michael's Hospital, University of Toronto, Toronto, Ontario, Canada. FAU - Akinkuolie, Akintunde O AU - Akinkuolie AO AD - Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. FAU - Paynter, Nina AU - Paynter N AD - Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. FAU - Glynn, Robert J AU - Glynn RJ AD - Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts3Harvard T. H. Chan School of Public Health, Boston, Massachusetts4Department of Biostatistics, Brigham and Women's Hospita. FAU - Ridker, Paul M AU - Ridker PM AD - Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts5Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. FAU - Mora, Samia AU - Mora S AD - Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts5Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. LA - eng SI - ClinicalTrials.gov/NCT00239681 GR - R01 HL117861/HL/NHLBI NIH HHS/United States GR - T32 HL007575/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PL - United States TA - JAMA Cardiol JT - JAMA cardiology JID - 101676033 RN - 0 (Cholesterol, LDL) RN - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors) RN - 0 (Lipoproteins) RN - 0 (Lipoproteins, HDL) RN - 0 (Lipoproteins, LDL) RN - 0 (Lipoproteins, VLDL) RN - 0 (Triglycerides) RN - 0 (very low density lipoprotein triglyceride) RN - 83MVU38M7Q (Rosuvastatin Calcium) RN - 9007-41-4 (C-Reactive Protein) SB - IM CIN - JAMA Cardiol. 2016 May 1;1(2):145-6. PMID: 27437884 MH - Aged MH - C-Reactive Protein/analysis MH - Cholesterol, LDL/blood MH - Diabetes Mellitus, Type 2/blood/*diagnosis/drug therapy MH - Female MH - Humans MH - Hydroxymethylglutaryl-CoA Reductase Inhibitors/*administration & dosage MH - Insulin Resistance/*physiology MH - Lipoproteins/drug effects MH - Lipoproteins, HDL/*antagonists & inhibitors/blood MH - Lipoproteins, LDL/*antagonists & inhibitors/blood MH - Lipoproteins, VLDL/drug effects MH - Male MH - Middle Aged MH - Outcome Assessment, Health Care MH - Risk Factors MH - Rosuvastatin Calcium/*administration & dosage MH - Triglycerides PMC - PMC4918085 MID - NIHMS766680 EDAT- 2016/06/28 06:00 MHDA- 2018/04/24 06:00 PMCR- 2017/05/01 CRDT- 2016/06/28 06:00 PHST- 2016/06/28 06:00 [entrez] PHST- 2016/06/28 06:00 [pubmed] PHST- 2018/04/24 06:00 [medline] PHST- 2017/05/01 00:00 [pmc-release] AID - 2513304 [pii] AID - 10.1001/jamacardio.2016.0096 [doi] PST - ppublish SO - JAMA Cardiol. 2016 May 1;1(2):136-45. doi: 10.1001/jamacardio.2016.0096.