Gender differences in the progression of target organ damage in patients with increased insulin resistance: the LOD-DIABETES study

Manuel Ángel Gómez-Marcos, José Ignacio Recio-Rodríguez, Leticia Gómez-Sánchez, Cristina Agudo-Conde, Emiliano Rodríguez-Sanchez, JoseAngel Maderuelo-Fernandez, Marta Gomez-Sanchez, Luís García-Ortiz, LOD-DIABETES Group, Manuel A Gómez-Marcos, Cristina Agudo-Conde, Leticia Gomez-Sanchez, Marta Gomez-Sanchez, Carmen Castaño-Sanchez, Carmela Rodriguez-Martin, Benigna Sanchez-Salgado, Angela de Cabo Laso, Emiliano Rodriguez-Sanchez, Jose Angel Maderuelo-Fernandez, Emilio Ramos-Delgado, Carmen Patino-Alonso, Jose I Recio-Rodriguez, Luis Garcia-Ortiz, Manuel Ángel Gómez-Marcos, José Ignacio Recio-Rodríguez, Leticia Gómez-Sánchez, Cristina Agudo-Conde, Emiliano Rodríguez-Sanchez, JoseAngel Maderuelo-Fernandez, Marta Gomez-Sanchez, Luís García-Ortiz, LOD-DIABETES Group, Manuel A Gómez-Marcos, Cristina Agudo-Conde, Leticia Gomez-Sanchez, Marta Gomez-Sanchez, Carmen Castaño-Sanchez, Carmela Rodriguez-Martin, Benigna Sanchez-Salgado, Angela de Cabo Laso, Emiliano Rodriguez-Sanchez, Jose Angel Maderuelo-Fernandez, Emilio Ramos-Delgado, Carmen Patino-Alonso, Jose I Recio-Rodriguez, Luis Garcia-Ortiz

Abstract

Background: The purpose of this study was to analyze the evolution of vascular, cardiac and renal target organ damage (TOD) in patients with increased insulin resistance over a 3.5 year follow-up and to investigate gender difference and factors that influence its progression.

Methods: We performed a prospective observational study involving 112 patients (71 men, 41 women) who were followed for 3.5 years. Measurements included blood pressure, blood glucose, lipids, smoking, body mass index (BMI) and HOMA-Ir Vascular TOD included carotid intima-media thickness (IMT), pulse wave velocity (PWV) and ankle/brachial index (ABI). Cardiac TOD included Cornell voltage-duration product and Sokolow. Renal TOD included creatinine, glomerular filtration and albumin/creatinine ratio.

Results: The IMT increased in both genders. Each year, the IMT increased 0.005 mm in men and 0.011 in women and the PWV 0.024 and 0.020 m/sec, respectively. The highest increase was in women with type 2 diabetes mellitus, who had an increase in TOD carotid (40%), PWV (24%) and renal TOD (20 %). Multiple regression analysis, after adjusting for age and gender, showed a negative association between duration since diabetes diagnosis and ABI (β = -0.006; p = 0.017) and between BMI and glomerular filtration (β = -0.813; p = 0.014). HbA1c was positively associated with PWV (β = 0.501; p = 0.014).

Conclusions: This study showed that the progression of vascular and renal TOD differs by gender. The increase in vascular and renal TOD was higher in women, especially in diabetic women. The PWV increase showed a positive association with mean HbA1c levels during the follow-up. Glomerular filtration was associated with BMI and the ABI was associated with duration since type 2 diabetes mellitus diagnosis.

Trial registration: Clinical Trials.gov Identifier NCT01065155.

Figures

Fig. 1
Fig. 1
Study flow chart. The subjects analyzed each year are presented in the flow chart. Additional information includes cardiovascular events in each group and evaluation of patients by gender
Fig. 2
Fig. 2
Changes in target organ damage over time during 3.5 years of follow-up. a Target organ damage (TOD) in men and in women; b Vascular TOD in men and in women. IMT intima media thickness, cf-PWV carotid femoral pulse wave velocity, ABI ankle brachial index. In men, the vascular TOD was significantly different between the final and baseline assessment and the 2nd and 3rd assessments (p < 0.05). The cf-PWV TOD was also significantly different between the final and baseline assessment (p < 0.05). In women, the vascular TOD was significantly different between the 2nd and 3rd assessments (p < 0.05). There was also a significant difference in the IMT TOD between the baseline and 2nd assessment and between the 2nd and 3rd assessment (p < 0.05). The cf-PWV TOD was significantly different between the 2nd and 3rd assessment (p < 0.05)

References

    1. Barnett KN, Ogston SA, McMurdo ME, Morris AD, Evans JM. A 12-year follow-up study of all-cause and cardiovascular mortality among 10,532 people newly diagnosed with Type 2 diabetes in Tayside, Scotland. Diabet Med. 2010;27(10):1124–1129. doi: 10.1111/j.1464-5491.2010.03075.x.
    1. Novo S, Peritore A, Guarneri FP, Corrado E, Macaione F, Evola S, Novo G. Metabolic syndrome (MetS) predicts cardio and cerebrovascular events in a 20 years follow-up. A prospective study. Atherosclerosis. 2012;223(2):468–472. doi: 10.1016/j.atherosclerosis.2012.05.018.
    1. Novo S, Peritore A, Trovato RL, Guarneri FP, Di Lisi D, Muratori I, Novo G. Preclinical atherosclerosis and metabolic syndrome increase cardio- and cerebrovascular events rate: a 20-year follow up. Cardiovasc Diabetol. 2013;12:155. doi: 10.1186/1475-2840-12-155.
    1. Ben-Shlomo Y, Spears M, Boustred C, May M, Anderson SG, Benjamin EJ, Boutouyrie P, Cameron J, Chen CH, Cruickshank JK. Aortic pulse wave velocity improves cardiovascular event prediction: an individual participant meta-analysis of prospective observational data from 17,635 subjects. J Am Coll Cardiol. 2014;63(7):636–646. doi: 10.1016/j.jacc.2013.09.063.
    1. Maeda Y, Inoguchi T, Etoh E, Kodama Y, Sasaki S, Sonoda N, Nawata H, Shimabukuro M, Takayanagi R. Brachial-ankle pulse wave velocity predicts all-cause mortality and cardiovascular events in patients with diabetes: the Kyushu Prevention Study of Atherosclerosis. Diabetes Care. 2014;37(8):2383–2390. doi: 10.2337/dc13-1886.
    1. van den Oord SC, Sijbrands EJ, ten Kate GL, van Klaveren D, van Domburg RT, van der Steen AF, Schinkel AF. Carotid intima-media thickness for cardiovascular risk assessment: systematic review and meta-analysis. Atherosclerosis. 2013;228(1):1–11. doi: 10.1016/j.atherosclerosis.2013.01.025.
    1. Somaratne JB, Whalley GA, Poppe KK, ter Bals MM, Wadams G, Pearl A, Bagg W, Doughty RN. Screening for left ventricular hypertrophy in patients with type 2 diabetes mellitus in the community. Cardiovasc Diabetol. 2011;10:29. doi: 10.1186/1475-2840-10-29.
    1. Rodriguez-Poncelas A, Coll-De Tuero G, Turro-Garriga O, Barrot-de la Puente J, Franch-Nadal J, Mundet-Tuduri X. Impact of chronic kidney disease on the prevalence of cardiovascular disease in patients with type 2 diabetes in Spain: PERCEDIME2 study. BMC Nephrol. 2014;15:150. doi: 10.1186/1471-2369-15-150.
    1. Fox CS, Matsushita K, Woodward M, Bilo HJ, Chalmers J, Heerspink HJ, Lee BJ, Perkins RM, Rossing P, Sairenchi T, et al. Associations of kidney disease measures with mortality and end-stage renal disease in individuals with and without diabetes: a meta-analysis. Lancet. 2012;380(9854):1662–1673. doi: 10.1016/S0140-6736(12)61350-6.
    1. Cosson E, Nguyen MT, Chanu B, Banu I, Chiheb S, Balta C, Takbou K, Valensi P. Cardiovascular risk prediction is improved by adding asymptomatic coronary status to routine risk assessment in type 2 diabetic patients. Diabetes Care. 2011;34(9):2101–2107. doi: 10.2337/dc11-0480.
    1. Anand SS, Islam S, Rosengren A, Franzosi MG, Steyn K, Yusufali AH, Keltai M, Diaz R, Rangarajan S, Yusuf S. Risk factors for myocardial infarction in women and men: insights from the INTERHEART study. Eur Heart J. 2008;29(7):932–940. doi: 10.1093/eurheartj/ehn018.
    1. Huxley R, Barzi F, Woodward M. Excess risk of fatal coronary heart disease associated with diabetes in men and women: meta-analysis of 37 prospective cohort studies. BMJ. 2006;332(7533):73–78. doi: 10.1136/bmj.38678.389583.7C.
    1. Cuspidi C, Rescaldani M, Sala C, Negri F, Grassi G, Mancia G. Prevalence of electrocardiographic left ventricular hypertrophy in human hypertension: an updated review. J Hypertens. 2012;30(11):2066–2073. doi: 10.1097/HJH.0b013e32835726a3.
    1. Fowkes FG, Murray GD, Butcher I, Heald CL, Lee RJ, Chambless LE, Folsom AR, Hirsch AT, Dramaix M, deBacker G, et al. Ankle brachial index combined with Framingham Risk Score to predict cardiovascular events and mortality: a meta-analysis. JAMA. 2008;300(2):197–208. doi: 10.1001/jama.300.2.197.
    1. Gottsäter M, Östling G, Persson M, Engström G, Melander O, Nilsson PM. Non-hemodynamic predictors of arterial stiffness after 17 years of follow-up: the Malmo Diet and Cancer study. J Hypertens. 2015;33(5):957–965. doi: 10.1097/HJH.0000000000000520.
    1. Katakami N, Osonoi T, Takahara M, Saitou M, Matsuoka TA, Yamasaki Y, Shimomura I. Clinical utility of brachial-ankle pulse wave velocity in the prediction of cardiovascular events in diabetic patients. Cardiovasc Diabetol. 2014;13(128). doi:10.1186/s12933-014-0128-5.
    1. Novo S, Peritore A, Trovato RL, Guarneri FP, Di Lisi D, Muratori I, Novo G. Preclinical atherosclerosis and metabolic syndrome increase cardio- and cerebrovascular events rate: a 20-year follow up. Cardiovasc Diabetol. 2013;12(155). doi:10.1186/1475-2840-12-155.
    1. Fang FS, Liu MY, Cheng XL, Zhong WW, Miao XY, Li J, Li CL, Tian H. Insulin resistance correlates with the arterial stiffness before glucose intolerance. Intern Med. 2014;53(3):189–194. doi: 10.2169/internalmedicine.53.0690.
    1. Noon JP, Trischuk TC, Gaucher SA, Galante S, Scott RL. The effect of age and gender on arterial stiffness in healthy Caucasian Canadians. J Clin Nurs. 2008;17(17):2311–2317. doi: 10.1111/j.1365-2702.2007.02155.x.
    1. Greve SV, Marie KB, Blyme A, Sehestedt T, Hansen TW, Rassmusen S, Vishram JKK, Ibsen H, Torp-Pedersen C, Olsen MH. Association between albuminuria, atherosclerotic plaques, elevated pulse wave velocity, age, risk category and prognosis in apparently healthy individuals. J Hypertens. 2014;32(5):1034–1041. doi: 10.1097/HJH.0000000000000147.
    1. Timóteo AT, Carmo MM, Ferreira RC. Can metabolic syndrome presence predict carotid intima-media thickness? J Clin Hypertens. 2012;14(8):507–513. doi: 10.1111/j.1751-7176.2012.00630.x.
    1. Tripolt NJ, Narath SH, Eder M, Pieber TR, Wascher TC, Sourij H. Multiple risk factor intervention reduces carotid atherosclerosis in patients with type 2 diabetes. Cardiovasc Diabetol. 2014;13(95):1475–2840.
    1. Ydin Y, Berker D, Ustün I, Gül K, Erden G, Kutlucan A, Yilmaz AL, Güler S. Evaluation of carotid intima media thickness in impaired fasting glucose and impaired glucose tolerance. Minerva Endocrinol. 2011;36(3):171–179.
    1. Lorenz MW, Polak JF, Kavousi M, Mathiesen EB, Volzke H, Tuomainen TP, Sander D, Plichart M, Catapano AL, Robertson CM, et al. Carotid intima-media thickness progression to predict cardiovascular events in the general population (the PROG-IMT collaborative project): a meta-analysis of individual participant data. Lancet. 2012;379(9831):2053–2062. doi: 10.1016/S0140-6736(12)60441-3.
    1. Mt F, Nc L, Cr C, Gf S. Correlates of aortic stiffness progression in patients with type 2 diabetes: importance of glycemic control: the Rio de Janeiro type 2 diabetes cohort study. Diabetes Care. 2015;38(5):897–904. doi: 10.2337/dc14-2791.
    1. Medina-Escobedo M, Romero-Campos S, Sansores-Espana D, Viveros-Cortes A, Villanueva-Jorge S. Changes in body composition according to kidney damage in patients with type 2 diabetes mellitus. Rev Med Inst Mex Seguro Soc. 2013;51(1):26–33.
    1. de Hauteclocque A, Ragot S, Slaoui Y, Gand E, Miot A, Sosner P, Halimi JM, Zaoui P, Rigalleau V, Roussel R, et al. The influence of sex on renal function decline in people with Type 2 diabetes. Diabet Med. 2014;31(9):1121–1128. doi: 10.1111/dme.12478.
    1. Ring M, Eriksson MJ, Fritz T, Nyberg G, Östenson CG, Krook A, Zierath JR, Caidahl K. Influence of physical activity and gender on arterial function in type 2 diabetes, normal and impaired glucose tolerance. Diab Vasc Dis Res. 2015;12(5):315–324. doi: 10.1177/1479164115588548.
    1. Gomez-Marcos MA, Recio-Rodriguez JI, Rodriguez-Sanchez E, Castano-Sanchez Y, deCabo-Laso A, Sanchez-Salgado B, Rodriguez-Martin C, Castano-Sanchez C, Gomez-Sanchez L, Garcia-Ortiz L. Central blood pressure and pulse wave velocity: relationship to target organ damage and cardiovascular morbidity-mortality in diabetic patients or metabolic syndrome. An observational prospective study. LOD-DIABETES study protocol. BMC Public Health. 2010;10:143. doi: 10.1186/1471-2458-10-143.
    1. American Diabetes Association Diagnosis and classification of diabetes mellitus. Diabetes Care. 2010;33(Suppl 1):S62–S69. doi: 10.2337/dc10-S062.
    1. Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH, Franklin BA, Gordon DJ, Krauss RM, Savage PJ, Smith SC, Jr, et al. Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Circulation. 2005;112(17):2735–2752. doi: 10.1161/CIRCULATIONAHA.105.169404.
    1. World Medical Association Declaration of Helsinki ethical principles for medical research involving human subjects. JAMA. 2013;310(20):2191–2194. doi: 10.1001/jama.2013.281053.
    1. Mancia G, Fagard R, Narkiewicz K, Redon J, Zanchetti A, Bohm M, Christiaens T, Cifkova R, De Backer G, Dominiczak A, et al. 2013 ESH/ESC Guidelines for the management of arterial hypertension: the Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC) J Hypertens. 2013;31(7):1281–1357. doi: 10.1097/.
    1. Van Bortel LM, Laurent S, Boutouyrie P, Chowienczyk P, Cruickshank JK, De Backer T, Filipovsky J, Huybrechts S, Mattace-Raso FU, Protogerou AD, et al. Expert consensus document on the measurement of aortic stiffness in daily practice using carotid-femoral pulse wave velocity. J Hypertens. 2012;30(3):445–448. doi: 10.1097/HJH.0b013e32834fa8b0.
    1. Gomez-Marcos MA, Recio-Rodriguez JI, Patino-Alonso MC, Agudo-Conde C, Gomez-Sanchez L, Gomez-Sanchez M, Rodriguez-Sanchez E, Garcia-Ortiz L. Protocol for measuring carotid intima-media thickness that best correlates with cardiovascular risk and target organ damage. Am J Hypertens. 2012;25(9):955–961. doi: 10.1038/ajh.2012.72.
    1. Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med. 1999;130(6):461–470. doi: 10.7326/0003-4819-130-6-199903160-00002.
    1. Okin PM, Roman MJ, Devereux RB, Kligfield P. Electrocardiographic identification of increased left ventricular mass by simple voltage-duration products. J Am Coll Cardiol. 1995;25(2):417–423. doi: 10.1016/0735-1097(94)00371-V.
    1. Zhao B, Liu Y, Zhang Y, Chen Y, Yang Z, Zhu Y, Zhan W. Gender difference in carotid intima-media thickness in type 2 diabetic patients: a 4-year follow-up study. Cardiovasc Diabetol. 2012;16(11):11–51.
    1. Dantas APV, Fortes ZB, de Carvalho MHC. Vascular disease in diabetic women: why do they miss the female protection? Exp Diabetes Res. 2012;570598(10):3.
    1. De Angelis L, Millasseau SC, Smith A, Viberti G, Jones RH, Ritter JM, Chowienczyk PJ. Sex differences in age-related stiffening of the aorta in subjects with type 2 diabetes. Hypertension. 2004;44(1):67–71. doi: 10.1161/01.HYP.0000130482.81883.fd.
    1. Ito H, Komatsu Y, Mifune M, Antoku S, Ishida H, Takeuchi Y, Togane M. The estimated GFR, but not the stage of diabetic nephropathy graded by the urinary albumin excretion, is associated with the carotid intima-media thickness in patients with type 2 diabetes mellitus: a cross-sectional study. Cardiovasc Diabetol. 2010;9:18. doi: 10.1186/1475-2840-9-18.
    1. Gyárfás I, Keltai M, Salim Y. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries in a case-control study based on the INTERHEART study. Orv Hetil. 2006;147(15):675–686.
    1. Marlatt KL, Kelly AS, Steinberger J, Dengel DR. The influence of gender on carotid artery compliance and distensibility in children and adults. J Clin Ultrasound. 2013;41(6):340–346. doi: 10.1002/jcu.22015.
    1. Rossi P, Frances Y, Kingwell BA, Ahimastos AA. Gender differences in artery wall biomechanical properties throughout life. J Hypertens. 2011;29(6):1023–1033. doi: 10.1097/HJH.0b013e328344da5e.
    1. Anoop S, Misra A, Bhardwaj S, Gulati S. High body fat and low muscle mass are associated with increased arterial stiffness in Asian Indians in North India. J Diabetes Complications 2014.
    1. Santosa S, Jensen MD. The sexual dimorphism of lipid kinetics in humans. Front Endocrinol (Lausanne) 2015;6:103.
    1. Gomez-Marcos MA, Recio-Rodriguez JI, Patino-Alonso MC, Agudo-Conde C, Gomez-Sanchez L, Rodriguez-Sanchez E, Gomez-Sanchez M, Martinez-Vizcaino V, Garcia-Ortiz L. Relationships between high-sensitive C-reactive protein and markers of arterial stiffness in hypertensive patients. Differences by sex. BMC Cardiovasc Disord. 2012;12:37. doi: 10.1186/1471-2261-12-37.

Source: PubMed

Patrocinadores e Colaboradores

Condições médicas

Intervenções de drogas

3
Se inscrever