Skip to main content
Top
Published in: Diabetology & Metabolic Syndrome 1/2013

Open Access 01-12-2013 | Research

Young Hispanics at risk of type 2 diabetes display endothelial activation, subclinical inflammation and alterations of coagulation and fibrinolysis

Authors: Carlos O Mendivil, Ludivina Robles-Osorio, Edward S Horton, Osama Hamdy, Augusto Enrique Caballero

Published in: Diabetology & Metabolic Syndrome | Issue 1/2013

Login to get access

Abstract

Background

Hispanics have a high rate of diabetes that exposes them to an increased risk of cardiovascular disease. We hypothesized that many of the pathophysiological mechanisms that cause atherosclerotic disease may be present in young Hispanics who do not have clinical diabetes but are at increased risk of developing it.

Methods

We studied 36 young Hispanic adults without diabetes (ages 18–40). Seventeen participants were at increased risk of developing type 2 diabetes given by overweight and a family history of diabetes on one or both parents (at risk group). Nineteen participants with normal body-mass index and no parental history of diabetes constituted the control group. We measured and compared plasma markers of endothelial dysfunction, disturbed coagulation and fibrinolysis, subclinical inflammation and adipose tissue dysfunction in the at risk and control groups.

Results

Participants at risk of diabetes were more insulin-resistant according to different indicators, and had significantly higher levels of soluble intercellular adhesion molecule-1 (sICAM-1), tissue plasminogen activator (tPA), inhibitor of plasminogen activator-1 (PAi-1), high sensitivity C-reactive protein and free fatty acids, signaling the presence of multiple proatherogenic alterations despite the absence of overt diabetes. Levels of the prothrombotic molecule PAi-1 were most elevated in participants who were not only at risk of diabetes by the study definition, but also abdominally obese.

Conclusions

Young adult Hispanics at risk of type 2 diabetes but without overt disease already bear considerably high levels of markers reflecting processes that lead to the development of atherosclerotic cardiovascular disease.
Appendix
Available only for authorised users
Literature
3.
go back to reference Kaur J, Singh P, Sowers JR: Diabetes and cardiovascular diseases. Am J Ther. 2002, 9: 510-515. 10.1097/00045391-200211000-00009.CrossRefPubMed Kaur J, Singh P, Sowers JR: Diabetes and cardiovascular diseases. Am J Ther. 2002, 9: 510-515. 10.1097/00045391-200211000-00009.CrossRefPubMed
4.
5.
go back to reference Bild DE, Detrano R, Peterson D, Guerci A, Liu K, Shahar E, Ouyang P, Jackson S, Saad MF: Ethnic differences in coronary calcification: the Multi-Ethnic Study of Atherosclerosis (MESA). Circulation. 2005, 111: 1313-1320. 10.1161/01.CIR.0000157730.94423.4B.CrossRefPubMed Bild DE, Detrano R, Peterson D, Guerci A, Liu K, Shahar E, Ouyang P, Jackson S, Saad MF: Ethnic differences in coronary calcification: the Multi-Ethnic Study of Atherosclerosis (MESA). Circulation. 2005, 111: 1313-1320. 10.1161/01.CIR.0000157730.94423.4B.CrossRefPubMed
6.
7.
go back to reference Hairston KG, Scherzinger A, Foy C, Hanley AJ, McCorkle O, Haffner S, Norris JM, Bryer-Ash M, Wagenknecht LE: Five-year change in visceral adipose tissue quantity in a minority cohort: the Insulin Resistance Atherosclerosis Study (IRAS) family study. Diabetes Care. 2009, 32: 1553-1555. 10.2337/dc09-0336.PubMedCentralCrossRefPubMed Hairston KG, Scherzinger A, Foy C, Hanley AJ, McCorkle O, Haffner S, Norris JM, Bryer-Ash M, Wagenknecht LE: Five-year change in visceral adipose tissue quantity in a minority cohort: the Insulin Resistance Atherosclerosis Study (IRAS) family study. Diabetes Care. 2009, 32: 1553-1555. 10.2337/dc09-0336.PubMedCentralCrossRefPubMed
8.
go back to reference Libby P, Ridker PM, Hansson GK, Leducq Transatlantic Network on Atherothrombosis: Inflammation in atherosclerosis: from pathophysiology to practice. J Am Coll Cardiol. 2009, 54: 2129-2138. 10.1016/j.jacc.2009.09.009.PubMedCentralCrossRefPubMed Libby P, Ridker PM, Hansson GK, Leducq Transatlantic Network on Atherothrombosis: Inflammation in atherosclerosis: from pathophysiology to practice. J Am Coll Cardiol. 2009, 54: 2129-2138. 10.1016/j.jacc.2009.09.009.PubMedCentralCrossRefPubMed
9.
go back to reference Martín-Ventura JL, Blanco-Colio LM, Tuñón J, Muñoz-García B, Madrigal-Matute J, Moreno JA, de Céniga M V, Egido J: Biomarkers in cardiovascular medicine. Rev Esp Cardiol. 2009, 62: 677-688. 10.1016/S0300-8932(09)71335-1.CrossRefPubMed Martín-Ventura JL, Blanco-Colio LM, Tuñón J, Muñoz-García B, Madrigal-Matute J, Moreno JA, de Céniga M V, Egido J: Biomarkers in cardiovascular medicine. Rev Esp Cardiol. 2009, 62: 677-688. 10.1016/S0300-8932(09)71335-1.CrossRefPubMed
10.
go back to reference Hu FB, Meigs JB, Li TY, Rifai N, Manson JE: Inflammatory markers and risk of developing type 2 diabetes in women. Diabetes. 2004, 53: 693-700. 10.2337/diabetes.53.3.693.CrossRefPubMed Hu FB, Meigs JB, Li TY, Rifai N, Manson JE: Inflammatory markers and risk of developing type 2 diabetes in women. Diabetes. 2004, 53: 693-700. 10.2337/diabetes.53.3.693.CrossRefPubMed
11.
go back to reference Meigs JB, Hu FB, Rifai N, Manson JE: Biomarkers of endothelial dysfunction and risk of type 2 diabetes mellitus. JAMA. 2004, 291: 1978-1986. 10.1001/jama.291.16.1978.CrossRefPubMed Meigs JB, Hu FB, Rifai N, Manson JE: Biomarkers of endothelial dysfunction and risk of type 2 diabetes mellitus. JAMA. 2004, 291: 1978-1986. 10.1001/jama.291.16.1978.CrossRefPubMed
12.
go back to reference Caballero AE: Metabolic and vascular abnormalities in subjects at risk for type 2 diabetes: the early start of a dangerous situation. Arch Med Res. 2005, 36: 241-249. 10.1016/j.arcmed.2005.03.013.CrossRefPubMed Caballero AE: Metabolic and vascular abnormalities in subjects at risk for type 2 diabetes: the early start of a dangerous situation. Arch Med Res. 2005, 36: 241-249. 10.1016/j.arcmed.2005.03.013.CrossRefPubMed
13.
go back to reference Caballero AE: Endothelial dysfunction, inflammation, and insulin resistance: A Focus on Subjects at risk for type 2 diabetes. Curr Diabetes Rep. 2004, 4: 237-246. 10.1007/s11892-004-0074-9.CrossRef Caballero AE: Endothelial dysfunction, inflammation, and insulin resistance: A Focus on Subjects at risk for type 2 diabetes. Curr Diabetes Rep. 2004, 4: 237-246. 10.1007/s11892-004-0074-9.CrossRef
14.
go back to reference Brinkworth GD, Noakes M, Keogh JB, Luscombe ND, Wittert GA, Clifton PM: Long-term effects of a high-protein, low-carbohydrate diet on weight control and cardiovascular risk markers in obese hyperinsulinemic subjects. Int J Obes Relat Metab Disord. 2004, 28: 661-670. 10.1038/sj.ijo.0802617.CrossRefPubMed Brinkworth GD, Noakes M, Keogh JB, Luscombe ND, Wittert GA, Clifton PM: Long-term effects of a high-protein, low-carbohydrate diet on weight control and cardiovascular risk markers in obese hyperinsulinemic subjects. Int J Obes Relat Metab Disord. 2004, 28: 661-670. 10.1038/sj.ijo.0802617.CrossRefPubMed
15.
go back to reference Caballero AE, Arora S, Saouaf R, Lim SC, Smakowski P, Park JY, King GL, LoGerfo FW, Horton ES, Veves A: Microvascular and macrovascular reactivity is reduced in subjects at risk for type 2 diabetes. Diabetes. 1999, 48: 1856-1862. 10.2337/diabetes.48.9.1856.CrossRefPubMed Caballero AE, Arora S, Saouaf R, Lim SC, Smakowski P, Park JY, King GL, LoGerfo FW, Horton ES, Veves A: Microvascular and macrovascular reactivity is reduced in subjects at risk for type 2 diabetes. Diabetes. 1999, 48: 1856-1862. 10.2337/diabetes.48.9.1856.CrossRefPubMed
16.
go back to reference Caballero AE, Bousquet-Santos K, Robles-Osorio L, Montagnani V, Soodini G, Porramatikul S, Hamdy O, Nobrega AC, Horton ES: Overweight Latino children and adolescents have marked endothelial dysfunction and subclinical vascular inflammation in association with excess body fat and insulin resistance. Diabetes Care. 2008, 31: 576-582.CrossRefPubMed Caballero AE, Bousquet-Santos K, Robles-Osorio L, Montagnani V, Soodini G, Porramatikul S, Hamdy O, Nobrega AC, Horton ES: Overweight Latino children and adolescents have marked endothelial dysfunction and subclinical vascular inflammation in association with excess body fat and insulin resistance. Diabetes Care. 2008, 31: 576-582.CrossRefPubMed
17.
go back to reference Roberts WC: The Friedewald-Levy-Fredrickson formula for calculating low-density lipoprotein cholesterol, the basis for lipid-lowering therapy. Am J Cardiol. 1988, 62: 345-346. 10.1016/0002-9149(88)90248-2.CrossRefPubMed Roberts WC: The Friedewald-Levy-Fredrickson formula for calculating low-density lipoprotein cholesterol, the basis for lipid-lowering therapy. Am J Cardiol. 1988, 62: 345-346. 10.1016/0002-9149(88)90248-2.CrossRefPubMed
18.
go back to reference Matthews JN, Altman DG, Campbell MJ, Royston P: Analysis of serial measurements in medical research. BMJ. 1990, 300: 230-235. 10.1136/bmj.300.6719.230.PubMedCentralCrossRefPubMed Matthews JN, Altman DG, Campbell MJ, Royston P: Analysis of serial measurements in medical research. BMJ. 1990, 300: 230-235. 10.1136/bmj.300.6719.230.PubMedCentralCrossRefPubMed
19.
go back to reference Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC: Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985, 28: 412-419. 10.1007/BF00280883.CrossRefPubMed Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC: Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985, 28: 412-419. 10.1007/BF00280883.CrossRefPubMed
20.
go back to reference Constans J, Conri C: Circulating markers of endothelial function in cardiovascular disease. Clin Chim Acta. 2006, 368: 33-47. 10.1016/j.cca.2005.12.030.CrossRefPubMed Constans J, Conri C: Circulating markers of endothelial function in cardiovascular disease. Clin Chim Acta. 2006, 368: 33-47. 10.1016/j.cca.2005.12.030.CrossRefPubMed
21.
go back to reference Wu KK, Aleksic N, Ballantyne CM, Ahn C, Juneja H, Boerwinkle E: Interaction between soluble thrombomodulin and intercellular adhesion molecule-1 in predicting risk of coronary heart disease. Circulation. 2003, 107: 1729-1732. 10.1161/01.CIR.0000064894.97094.4F.CrossRefPubMed Wu KK, Aleksic N, Ballantyne CM, Ahn C, Juneja H, Boerwinkle E: Interaction between soluble thrombomodulin and intercellular adhesion molecule-1 in predicting risk of coronary heart disease. Circulation. 2003, 107: 1729-1732. 10.1161/01.CIR.0000064894.97094.4F.CrossRefPubMed
22.
go back to reference Ridker PM, Hennekens CH, Roitman-Johnson B, Stampfer MJ, Allen J: Plasma concentration of soluble intercellular adhesion molecule 1 and risks of future myocardial infarction in apparently healthy men. Lancet. 1998, 351: 88-92. 10.1016/S0140-6736(97)09032-6.CrossRefPubMed Ridker PM, Hennekens CH, Roitman-Johnson B, Stampfer MJ, Allen J: Plasma concentration of soluble intercellular adhesion molecule 1 and risks of future myocardial infarction in apparently healthy men. Lancet. 1998, 351: 88-92. 10.1016/S0140-6736(97)09032-6.CrossRefPubMed
23.
go back to reference Hulthe J, Wikstrand J, Mattsson-Hulten L, Fagerberg B: Circulating ICAM-1 (intercellular cell-adhesion molecule 1) is associated with early stages of atherosclerosis development and with inflammatory cytokines in healthy 58-year-old men: the Atherosclerosis and Insulin Resistance (AIR) study. Clin Sci (Lond). 2002, 103: 123-129. 10.1042/CS20010366.CrossRef Hulthe J, Wikstrand J, Mattsson-Hulten L, Fagerberg B: Circulating ICAM-1 (intercellular cell-adhesion molecule 1) is associated with early stages of atherosclerosis development and with inflammatory cytokines in healthy 58-year-old men: the Atherosclerosis and Insulin Resistance (AIR) study. Clin Sci (Lond). 2002, 103: 123-129. 10.1042/CS20010366.CrossRef
24.
go back to reference Pradhan AD, Rifai N, Ridker PM: Soluble intercellular adhesion molecule-1, soluble vascular adhesion molecule-1, and the development of symptomatic peripheral arterial disease in men. Circulation. 2002, 106: 820-825. 10.1161/01.CIR.0000025636.03561.EE.CrossRefPubMed Pradhan AD, Rifai N, Ridker PM: Soluble intercellular adhesion molecule-1, soluble vascular adhesion molecule-1, and the development of symptomatic peripheral arterial disease in men. Circulation. 2002, 106: 820-825. 10.1161/01.CIR.0000025636.03561.EE.CrossRefPubMed
25.
go back to reference Ha H, Oh EY, Lee HB: The role of plasminogen activator inhibitor 1 in renal and cardiovascular diseases. Nat Rev Nephrol. 2009, 5: 203-211. 10.1038/nrneph.2009.15.CrossRefPubMed Ha H, Oh EY, Lee HB: The role of plasminogen activator inhibitor 1 in renal and cardiovascular diseases. Nat Rev Nephrol. 2009, 5: 203-211. 10.1038/nrneph.2009.15.CrossRefPubMed
26.
go back to reference De Pergola G, De Mitrio V, Giorgino F, Sciaraffia M, Minenna A, Di Bari L, Pannacciulli N, Giorgino R: Increase in both pro-thrombotic and anti-thrombotic factors in obese premenopausal women: relationship with body fat distribution. Int J Obes Relat Metab Disord. 1997, 21: 527-535. 10.1038/sj.ijo.0800435.CrossRefPubMed De Pergola G, De Mitrio V, Giorgino F, Sciaraffia M, Minenna A, Di Bari L, Pannacciulli N, Giorgino R: Increase in both pro-thrombotic and anti-thrombotic factors in obese premenopausal women: relationship with body fat distribution. Int J Obes Relat Metab Disord. 1997, 21: 527-535. 10.1038/sj.ijo.0800435.CrossRefPubMed
27.
go back to reference Barbato A, Iacone R, Tarantino G, Russo O, Sorrentino P, Avallone S, Galletti F, Farinaro E, Della Valle E, Strazzullo P, Olivetti Heart Study Research Group: Relationships of PAI-1 levels to central obesity and liver steatosis in a sample of adult male population in southern Italy. Intern Emerg Med. 2009, 4: 315-323. 10.1007/s11739-009-0240-9.CrossRefPubMed Barbato A, Iacone R, Tarantino G, Russo O, Sorrentino P, Avallone S, Galletti F, Farinaro E, Della Valle E, Strazzullo P, Olivetti Heart Study Research Group: Relationships of PAI-1 levels to central obesity and liver steatosis in a sample of adult male population in southern Italy. Intern Emerg Med. 2009, 4: 315-323. 10.1007/s11739-009-0240-9.CrossRefPubMed
28.
go back to reference Peverill RE, Teede HJ, Malan E, Kotsopoulos D, Smolich JJ, McGrath BP: Relationship of waist and hip circumference with coagulation and fibrinolysis in postmenopausal women. Clin Sci (Lond). 2007, 113: 383-391. 10.1042/CS20070084.CrossRef Peverill RE, Teede HJ, Malan E, Kotsopoulos D, Smolich JJ, McGrath BP: Relationship of waist and hip circumference with coagulation and fibrinolysis in postmenopausal women. Clin Sci (Lond). 2007, 113: 383-391. 10.1042/CS20070084.CrossRef
29.
go back to reference Caballero AE: Endothelial dysfunction in obesity and insulin resistance: a road to diabetes and heart disease. Obes Res. 2003, 11: 1278-1289. 10.1038/oby.2003.174.CrossRefPubMed Caballero AE: Endothelial dysfunction in obesity and insulin resistance: a road to diabetes and heart disease. Obes Res. 2003, 11: 1278-1289. 10.1038/oby.2003.174.CrossRefPubMed
30.
go back to reference Hu G, Jousilahti P, Tuomilehto J, Antikainen R, Sundvall J, Salomaa V: Association of serum C-reactive protein level with sex-specific type 2 diabetes risk: a prospective finnish study. J Clin Endocrinol Metab. 2009, 94: 2099-2105. 10.1210/jc.2008-2260.CrossRefPubMed Hu G, Jousilahti P, Tuomilehto J, Antikainen R, Sundvall J, Salomaa V: Association of serum C-reactive protein level with sex-specific type 2 diabetes risk: a prospective finnish study. J Clin Endocrinol Metab. 2009, 94: 2099-2105. 10.1210/jc.2008-2260.CrossRefPubMed
31.
go back to reference The Emerging Risk Factors Collaboration: C-reactive protein concentration and risk of coronary heart disease, stroke, and mortality: an individual participant meta-analysis. Lancet. 2010, 375: 132-140.PubMedCentralCrossRef The Emerging Risk Factors Collaboration: C-reactive protein concentration and risk of coronary heart disease, stroke, and mortality: an individual participant meta-analysis. Lancet. 2010, 375: 132-140.PubMedCentralCrossRef
32.
go back to reference Abeywardena MY, Leifert WR, Warnes KE, Varghese JN, Head RJ: Cardiovascular biology of interleukin-6. Curr Pharm Des. 2009, 15: 1809-1821. 10.2174/138161209788186290.CrossRefPubMed Abeywardena MY, Leifert WR, Warnes KE, Varghese JN, Head RJ: Cardiovascular biology of interleukin-6. Curr Pharm Des. 2009, 15: 1809-1821. 10.2174/138161209788186290.CrossRefPubMed
33.
go back to reference Ruan H, Lodish HF: Insulin resistance in adipose tissue: direct and indirect effects of tumor necrosis factor-alpha. Cytokine Growth Factor Rev. 2003, 14: 447-455. 10.1016/S1359-6101(03)00052-2.CrossRefPubMed Ruan H, Lodish HF: Insulin resistance in adipose tissue: direct and indirect effects of tumor necrosis factor-alpha. Cytokine Growth Factor Rev. 2003, 14: 447-455. 10.1016/S1359-6101(03)00052-2.CrossRefPubMed
34.
go back to reference International Expert Committee: International Expert Committee report on the role of the A1C assay in the diagnosis of diabetes. Diabetes Care. 2009, 32: 1327-1334.CrossRef International Expert Committee: International Expert Committee report on the role of the A1C assay in the diagnosis of diabetes. Diabetes Care. 2009, 32: 1327-1334.CrossRef
35.
go back to reference American Association of Clinical Endocrinologists Board of Directors; American College of Endocrinologists Board of Trustees: American Association of Clinical Endocrinologists/American College of Endocrinology statement on the use of hemoglobin A1c for the diagnosis of diabetes. Endocr Pract. 2010, 16: 155-156.CrossRef American Association of Clinical Endocrinologists Board of Directors; American College of Endocrinologists Board of Trustees: American Association of Clinical Endocrinologists/American College of Endocrinology statement on the use of hemoglobin A1c for the diagnosis of diabetes. Endocr Pract. 2010, 16: 155-156.CrossRef
Metadata
Title
Young Hispanics at risk of type 2 diabetes display endothelial activation, subclinical inflammation and alterations of coagulation and fibrinolysis
Authors
Carlos O Mendivil
Ludivina Robles-Osorio
Edward S Horton
Osama Hamdy
Augusto Enrique Caballero
Publication date
01-12-2013
Publisher
BioMed Central
Published in
Diabetology & Metabolic Syndrome / Issue 1/2013
Electronic ISSN: 1758-5996
DOI
https://doi.org/10.1186/1758-5996-5-37

Other articles of this Issue 1/2013

Diabetology & Metabolic Syndrome 1/2013 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine