Contrasting associations of insulin resistance with diabetes, cardiovascular disease and all-cause mortality in the elderly: PROSPER long-term follow-up

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• 作者：Paul Welsh (1)
  David Preiss (1)
  Suzanne M. Lloyd (2)
  Anton J. de Craen (3)
  J. Wouter Jukema (4)
  Rudi G. Westendorp (3)
  Brendan M. Buckley (5)
  Patricia M. Kearney (6)
  Andrew Briggs (7)
  David J. Stott (8)
  Ian Ford (2)
  Naveed Sattar (1)
  
• 关键词：All ; cause mortality ; Cardiovascular disease ; Insulin resistance ; Risk factors
• 刊名：Diabetologia
• 出版年：2014
• 出版时间：December 2014
• 年：2014
• 卷：57
• 期：12
• 页码：2513-2520
• 全文大小：225 KB
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  2. Sattar N, McConnachie A, Shaper AG et al (2008) Can metabolic syndrome usefully predict cardiovascular disease and diabetes? Outcome data from two prospective studies. Lancet 371:1927-935 CrossRef
  3. Preiss D, Welsh P, Murray HM et al (2010) Fasting plasma glucose in non-diabetic participants and the risk for incident cardiovascular events, diabetes, and mortality: results from WOSCOPS 15-year follow-up. Eur Heart J 31:1230-236 j/ehq095" target="_blank" title="It opens in new window">CrossRef
  4. Welsh P, Murray HM, Buckley BM et al (2009) Leptin predicts diabetes but not cardiovascular disease: results from a large prospective study in an elderly population. Diabetes Care 32:308-10 CrossRef
  5. Emerging Risk Factors Collaboration (2010) Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies. Lancet 375:2215-222 CrossRef
  6. Tsuchiya K, Tanaka J, Shuiqing Y et al (2012) FoxOs integrate pleiotropic actions of insulin in vascular endothelium to protect mice from atherosclerosis. Cell Metab 15:372-81 j.cmet.2012.01.018" target="_blank" title="It opens in new window">CrossRef
  7. DeFronzo RA (2010) Insulin resistance, lipotoxicity, type 2 diabetes and atherosclerosis: the missing links. The Claude Bernard Lecture 2009. Diabetologia 53:1270-287 CrossRef
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  9. Gast KB, Tjeerdema N, Stijnen T, Smit JW, Dekkers OM (2012) Insulin resistance and risk of incident cardiovascular events in adults without diabetes: meta-analysis. PLoS ONE 7:e52036 journal.pone.0052036" target="_blank" title="It opens in new window">CrossRef
  10. Shepherd J, Blauw GJ, Murphy MB et al (2002) PROspective Study of Pravastatin in the Elderly at Risk. Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. Lancet 360:1623-630 CrossRef
  11. Lloyd SM, Stott DJ, de Craen AJ et al (2013) Long-term effects of statin treatment in elderly people: extended follow-up of the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER). PLoS ONE 8:e72642 journal.pone.0072642" target="_blank" title="It opens in new window">CrossRef
  12. Shepherd J, Blauw GJ, Murphy MB et al (1999) The design of a prospective study of Pravastatin in the Elderly at Risk (PROSPER). PROSPER Study Group. Am J Cardiol 84:1192-197 CrossRef
  13. Sattar N, Murray HM, Welsh P et al (2009) Are markers of inflammation more strongly associated with risk for fatal than for nonfatal vascular events? PLoS Med 6:e1000099 journal.pmed.1000099" target="_blank" title="It opens in new window">CrossRef
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• 作者单位：Paul Welsh (1)
  David Preiss (1)
  Suzanne M. Lloyd (2)
  Anton J. de Craen (3)
  J. Wouter Jukema (4)
  Rudi G. Westendorp (3)
  Brendan M. Buckley (5)
  Patricia M. Kearney (6)
  Andrew Briggs (7)
  David J. Stott (8)
  Ian Ford (2)
  Naveed Sattar (1)
  
  1. British Heart Foundation Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, G12 8TA, UK
  2. Robertson Centre for Biostatistics, University of Glasgow, Glasgow, UK
  3. Department of Gerontology and Geriatrics, Leiden University Medical Centre, Leiden, The Netherlands
  4. Department of Cardiology, Leiden University Medical Centre, Leiden, The Netherlands
  5. Department of Pharmacology and Therapeutics, Cork University Hospital, Cork, Ireland
  6. Department of Epidemiology & Public Health, University College Cork, Cork, Ireland
  7. Institute of Health & Wellbeing, University of Glasgow, Glasgow, UK
  8. Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK
  
• ISSN：1432-0428

文摘

Aims/hypothesis Insulin resistance is commonly proposed as a precursor to both type 2 diabetes and cardiovascular disease (CVD), yet few studies have directly compared insulin resistance with both outcomes simultaneously and determined whether associations with each outcome differ in strength or are comparable. We assessed the association of fasting insulin and HOMA-IR with incident?CVD and diabetes in older people. Methods In the long-term follow-up of the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER) cohort, HOMA-IR measurement was available in 4,742 older people (70-2?years) without diabetes at baseline. Of these, 283 developed diabetes during the 3.2?year within-trial follow-up, while 1,943 all-cause deaths, 470 CHD deaths (identified from death records) and 590 fatal/non-fatal CVD events (identified from medical record linkage in the Scottish participants) occurred during an extended 8.6?years of total follow-up. Cause-specific Cox proportional-hazards models were fitted using multivariable models. Results Higher HOMA-IR was associated with incident diabetes: HR 4.80 (95% CI 3.14, 7.33) comparing extreme thirds after adjustment for confounders. However, HOMA-IR in the top third was not associated with all-cause mortality, CHD mortality or fatal/non-fatal CVD: HR 1.02 (95% CI 0.90, 1.17), 1.03 (0.79, 1.36) and 0.94 (0.74, 1.20), respectively. Results were similar when fasting insulin was considered as an exposure. Conclusions/interpretation Our data support insulin resistance as a predictor of diabetes in later life but, perhaps surprisingly, suggest this pathway is of negligible importance to CVD outcomes in the elderly.