Cardiac Risk:Insulin Resistance, Hypertension, & PAI-1

Summary

Principal Investigator: Abraham Thomas
Abstract: Patients with diabetes mellitus have an increased risk from cardiovascular morbidity and mortality that is similar to patients, without diabetes, who have had a previous myocardial infarction. Although many explanations for this increased risk have been proposed from studies, the risk for a specific individual is difficult to determine from these studies. Plasminogen activator inhibitor-1 (PAI-1) is an important peptide in the fibrinolytic-thrombotic pathway and elevated levels of PAI-1 have been shown to correlate with cardiovascular events, such as myocardial infarction. Thus, PAI-1 may be a marker for cardiovascular risk. The renin-angiotensin system (RAS) also has profound effects on the cardiovascular system and pharmacologic blockade of the RAS can affect cardiovascular disease. The RAS can also affect levels of greater insulin resistance and a more adverse lipid profile than other sub-groups. However, not every diabetic patient is at equal risk for cardiovascular events or for elevations in PAI-1 levels. Thus, there are environmental and genetic factors that predispose certain individuals to greater cardiovascular risk. A genetic predisposition compounded by adverse environmental factors may highlight those at greatest risk. Genetic polymorphisms in the RAS may increase the adverse cardiovascular risk in diabetic subjects by increasing PAI-1 plasma levels or by creating an adverse metabolic milieu. The studies highlighted in this proposal will categorize diabetic subjects by an intermediate phenotype of the RAS, first demonstrated in hypertensive subjects. The relationship of gene polymorphisms in the RAS and PAI-1 genes and intermediate phenotypes of PAI-1 levels, lipids, obesity, and insulin resistance will be determined. The knowledge of which genotypes and intermediate phenotypes predict a greater risk for cardiovascular risk in patients with diabetes may help identify those individuals at greatest risk, may be able to predict the risk for a specific individuals, and may also help define specific therapy to reduce that risk.
Funding Period: 2002-07-15 - 2009-06-30
more information: NIH RePORT

Top Publications

  1. pmc Inflammation and hypertension: the interplay of interleukin-6, dietary sodium, and the renin-angiotensin system in humans
    Bindu Chamarthi
    Division of Endocrinology, Diabetes and Hypertension, Brigham and Women s and Harvard Medical School, Boston, Massachusetts, USA
    Am J Hypertens 24:1143-8. 2011
  2. ncbi Insulin induces renal vasodilation, increases plasma renin activity, and sensitizes the renal vasculature to angiotensin receptor blockade in healthy subjects
    Todd S Perlstein
    Division of Endocrinology, Diabetes and Hypertension, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    J Am Soc Nephrol 18:944-51. 2007
  3. ncbi C-reactive protein gene variation and type 2 diabetes mellitus: a case-control study
    Robert Y L Zee
    Center for Cardiovascular Disease Prevention, Brigham and Women s Hospital and Harvard Medical School, 900 Commonwealth Avenue East, Boston, MA 02215, USA
    Atherosclerosis 197:931-6. 2008

Detail Information

Publications3

  1. pmc Inflammation and hypertension: the interplay of interleukin-6, dietary sodium, and the renin-angiotensin system in humans
    Bindu Chamarthi
    Division of Endocrinology, Diabetes and Hypertension, Brigham and Women s and Harvard Medical School, Boston, Massachusetts, USA
    Am J Hypertens 24:1143-8. 2011
    ..The aim of this study was to examine the relationship of IL-6 and renin-angiotensin system (RAS) activity in human hypertension...
  2. ncbi Insulin induces renal vasodilation, increases plasma renin activity, and sensitizes the renal vasculature to angiotensin receptor blockade in healthy subjects
    Todd S Perlstein
    Division of Endocrinology, Diabetes and Hypertension, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    J Am Soc Nephrol 18:944-51. 2007
    ..Further studies are warranted to address this balance in states of insulin resistance and the possible implications for the association of insulin resistance with risk for chronic kidney disease...
  3. ncbi C-reactive protein gene variation and type 2 diabetes mellitus: a case-control study
    Robert Y L Zee
    Center for Cardiovascular Disease Prevention, Brigham and Women s Hospital and Harvard Medical School, 900 Commonwealth Avenue East, Boston, MA 02215, USA
    Atherosclerosis 197:931-6. 2008
    ..C-reactive protein (CRP) gene variation, in particular an rs2794521 variant was recently associated with type 2 diabetes mellitus (T2DM) in Pima Indians...