Plasma triglyceride/HDL-cholesterol ratio, insulin resistance, and cardiometabolic risk in young adults

Studies in mature adults suggest that the plasma concentration ratio of triglyceride (TG)/HDL-cholesterol (HDL-C) provides a simple way to identify apparently healthy individuals who are insulin resistant (IR) and at increased cardiometabolic risk. This study extends these observations by examining the clinical utility of the TG/HDL-C ratio and the metabolic syndrome (MetS) in 2,244 healthy college students (17–24 years old) of Mexican Mestizo ancestry. The TG/HDL-C ratio separating the 25% with the highest value was used to identify IR and increased cardiometabolic risk. Cardiometabolic risk factors were more adverse in men and women whose TG/HDL-C ratios exceeded 3.5 and 2.5, respectively, and approximately one third were identified as being IR. The MetS identified fewer individuals as being IR, but their risk profile was accentuated. In conclusion, both a higher TG/HDL-C ratio and a diagnosis of the MetS identify young IR individuals with an increased cardiometabolic risk profile. The TG/HDL-C ratio identified a somewhat greater number of “high risk” subjects, whereas the MetS found a group whose risk profile was somewhat magnified. These findings suggest that the TG/HDL-C ratio may serve as a simple and clinically useful approach to identify apparently healthy, young individuals who are IR and at increased cardiometabolic risk. Studies in mature adults suggest that the plasma concentration ratio of triglyceride (TG)/HDL-cholesterol (HDL-C) provides a simple way to identify apparently healthy individuals who are insulin resistant (IR) and at increased cardiometabolic risk. This study extends these observations by examining the clinical utility of the TG/HDL-C ratio and the metabolic syndrome (MetS) in 2,244 healthy college students (17–24 years old) of Mexican Mestizo ancestry. The TG/HDL-C ratio separating the 25% with the highest value was used to identify IR and increased cardiometabolic risk. Cardiometabolic risk factors were more adverse in men and women whose TG/HDL-C ratios exceeded 3.5 and 2.5, respectively, and approximately one third were identified as being IR. The MetS identified fewer individuals as being IR, but their risk profile was accentuated. In conclusion, both a higher TG/HDL-C ratio and a diagnosis of the MetS identify young IR individuals with an increased cardiometabolic risk profile. The TG/HDL-C ratio identified a somewhat greater number of “high risk” subjects, whereas the MetS found a group whose risk profile was somewhat magnified. These findings suggest that the TG/HDL-C ratio may serve as a simple and clinically useful approach to identify apparently healthy, young individuals who are IR and at increased cardiometabolic risk. Evidence has been presented that the plasma concentration ratio of triglyceride (TG)/HDL-cholesterol (HDL-C) may provide a relatively simple way to identify apparently healthy insulin-resistant persons with increased cardiometabolic risk (1McLaughlin T. Reaven G. Abbasi F. Lamendola C. Saad M. Waters D. Simon J. Krauss R.M. Is there a simple way to identify insulin-resistant individuals at increased risk of cardiovascular disease?.Am. J. Cardiol. 2005; 96: 399-404Abstract Full Text Full Text PDF PubMed Scopus (440) Google Scholar, 2Salazar M.R. Carbajal H.A. Espeche W.G. Dulbecco C.A. Aizpurúa M. Marillet A.G. Echeverría R.F. Reaven G.M. Relationships among insulin resistance, obesity, diagnosis of the metabolic syndrome and cardio-metabolic risk.Diab. Vasc. Dis. Res. 2011; 8: 109-116Crossref PubMed Scopus (50) Google Scholar). However, there is evidence that the actual values of the ratio that best identifies such individuals will vary as a function of racial/ethnic background (3Sumner A.E. Finley K.B. Genovese D.J. Criqui M.H. Boston R.C. Fasting triglyceride and the triglyceride-HDL cholesterol ratios are not markers of insulin resistance in African Americans.Arch. Intern. Med. 2005; 165: 1395-1400Crossref PubMed Scopus (178) Google Scholar, 4Bovet P. Faeh D. Gabriel A. Tappy L. The prediction of insulin resistance with serum triglyceride and high-density lipoprotein cholesterol levels in an East African population.Arch. Intern. Med. 2006; 166: 1236-1237Crossref PubMed Scopus (34) Google Scholar, 5Sumner A.E. Harman J.L. Buxbaum S.G. Miller 3rd, B.V. Tambay A.V. Wyatt S.B. Taylor H.A. Rotimi C.N. Sarpong D.F. The triglyceride/high-density lipoprotein cholesterol ratio fails to predict insulin resistance in African-American women: an analysis of Jackson Heart Study.Metab. Syndr. Relat. Disord. 2010; 8: 511-514Crossref PubMed Scopus (46) Google Scholar, 6Kim-Dorner S.J. Deuster P.A. Zeno S.A. Remaley A.T. Poth M. Should triglycerides and the triglycerides to high-density lipoprotein cholesterol ratio be used as surrogates for insulin resistance?.Metabolism. 2010; 59: 299-304Abstract Full Text Full Text PDF PubMed Scopus (126) Google Scholar, 7Li C. Ford E.S. Meng Y.X. Mokdad A.H. Reaven G.M. Does the association of the triglyceride to high-density lipoprotein cholesterol ratio with fasting serum insulin differ by race/ethnicity?.Cardiovasc. Diabetol. 2008; 7: 4Crossref PubMed Scopus (163) Google Scholar). More recently, it has also been shown that the most useful TG/HDL-C cut-point to identify cardiometabolic risk is not the same in men and women (2Salazar M.R. Carbajal H.A. Espeche W.G. Dulbecco C.A. Aizpurúa M. Marillet A.G. Echeverría R.F. Reaven G.M. Relationships among insulin resistance, obesity, diagnosis of the metabolic syndrome and cardio-metabolic risk.Diab. Vasc. Dis. Res. 2011; 8: 109-116Crossref PubMed Scopus (50) Google Scholar). However, there is essentially no information as to whether age also modifies the ability of the TG/HDL-C ratio to identify apparently healthy individuals with increased cardiometabolic risk. The primary goal of this analysis was to address this issue, and it is based on data obtained in an apparently healthy population of young men and women, mean age of 19 years. Second, since the diagnostic category of the metabolic syndrome (MetS) is commonly used to identify cardiometabolic risk in apparently healthy individuals (3Sumner A.E. Finley K.B. Genovese D.J. Criqui M.H. Boston R.C. Fasting triglyceride and the triglyceride-HDL cholesterol ratios are not markers of insulin resistance in African Americans.Arch. Intern. Med. 2005; 165: 1395-1400Crossref PubMed Scopus (178) Google Scholar, 8Alberti K.G. Eckel R.H. Grundy S.M. Zimmet P.Z. Cleeman J.I. Donato K.A. Fruchart J.C. James W.P. Loria C.M. Smith Jr, S.C. et al.Harmonizing the metabolic syndrome: a joint interim statement of the international diabetes federation task force on epidemiology and prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; International Association for the Study of Obesity.Circulation. 2009; 120: 1640-1645Crossref PubMed Scopus (9986) Google Scholar), our second goal was to compare these two approaches to identify insulin resistance (IR) and associated cardiometabolic risk in a population of young adults. In support of this effort is the recent observation that the plasma concentration ratio of TG/HDL-C was an independent determinant of arterial stiffness in adolescents and young adults (9Urbina E.M. Khoury P.R. McCoy C.E. Dolan L.M. Daniels S.R. Kimball T.R. Triglyceride to HDL-C ratio and increased arterial stiffness in children, adolescents, and young adults.Pediatrics. 2013; 131: e1082-e1090Crossref PubMed Scopus (112) Google Scholar). This study presents results obtained from an epidemiological study from which data of a different nature have been published previously (10Jiménez-Flores J.R. Murguía-Romero M. Mendoza-Ramos M.I. Sigrist-Flores S. Rodríguez-Soriano N.Y. Ramírez-García L.I. Jesús-Sandoval R. álvarez-Gasca M.A. Orozco E. Villalobos-Molina R. et al.Metabolic syndrome occurrence in university students from México City: the binomium low HDL/waist circumference is the major prevalence factor.Open J. Prev. Med. 2012; 2: 177-182Crossref Google Scholar). The study sample included 2,244 first-year university students (1,545 women and 699 men), 17–24 years of age, from the México City metropolitan area. Data were obtained by the Multidisciplinary Group to Investigate Health and Academic Performance (GMISARA) of the Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México (UNAM) (10Jiménez-Flores J.R. Murguía-Romero M. Mendoza-Ramos M.I. Sigrist-Flores S. Rodríguez-Soriano N.Y. Ramírez-García L.I. Jesús-Sandoval R. álvarez-Gasca M.A. Orozco E. Villalobos-Molina R. et al.Metabolic syndrome occurrence in university students from México City: the binomium low HDL/waist circumference is the major prevalence factor.Open J. Prev. Med. 2012; 2: 177-182Crossref Google Scholar). GMISARA employed a complex, multistage, geographic-area design for collecting data from public universities in the metropolitan area (UNAM and Universidad Autónoma de la Ciudad de México, UACM). All students were informed about the study, and they signed an informed consent. The protocol was approved by the Institutional Ethics Committee, and samples were collected over four years (2009–2012). Participants were not aware of any disease by medical history, nor did physical examination reveal any disease of relevance to this study. GMISARA members were trained to conduct interviews for collecting reliable data, including demographic, socioeconomic, dietary, and health-related information. Medical and physiological measurements were performed and collected by GMISARA medical personnel, and laboratory measurements were performed by CARPERMOR, S.A. de C.V., an internationally certified laboratory. Students fasted overnight and were seen at either UNAM or UACM between 7 AM and 10 AM. Waist circumference (WC) was determined while participants were upright, and it was measured to the nearest 0.1 cm at minimal respiration following normal expiration, with a flexible measuring tape placed at the high point of the iliac crest. Diastolic blood pressure (DBP) and systolic blood pressure (SBP) values were obtained after participants were resting quietly in a sitting position for 5 min, and determination of the maximum inflation level (up to four consecutive blood pressure readings) was obtained with a standard aneroid sphygmomanometer (Model DS44, Welch Allyn). The maximum values of replicate systolic and diastolic measurements provided estimates of blood pressure values. Glucose, insulin, TG, and HDL-C concentrations were determined by standard methods (CARPERMOR, S.A. de C.V.). Men and women were divided into quartiles on the basis of their TG/HDL-C concentration ratios, and mean ± SD values were calculated. The 25% of the population with the highest TG/HDL-C ratio was defined as “abnormal,” and values for age, homeostasis model assessment - insulin resistance (HOMA-IR); quantitative insulin sensitivity check index (QUICKI); SBP and DBP; body mass index (BMI); WC; and glucose, HDL-C, and TG concentrations were compared between this quartile and the remaining three quartiles. HOMA-IR (11Matthews D.R. Hosker J.P. Rudenski A.S. Naylor B.A. Treacher D.F. Turner R.C. Homeostasis model assessment: insulin resistance and β-cell function from fasting plasma glucose and insulin concentrations in man.Diabetologia. 1985; 28: 412-419Crossref PubMed Scopus (25502) Google Scholar) and QUICKI (12Katz A. Nambi S.S. Mather K. Baron A.D. Follmann D.A. Sullivan G. Quon M.J. Quantitative insulin sensitivity check index: a simple, accurate method for assessing insulin sensitivity in humans.J. Clin. Endocrinol. Metab. 2000; 85: 2402-2410Crossref PubMed Scopus (3059) Google Scholar) were used as surrogate estimates of insulin resistance, and the quartile with the highest value was defined as being insulin resistant, a classification based on results of a prospective study (13Zavaroni I. Bonini L. Gasparini P. Barilli A.L. Zuccarelli A. Dall'Aglio E. Delsignore R. Reaven G.M. Hyperinsulinemia in a normal population as a predictor of non-insulin-dependent diabetes mellitus, hypertension, and coronary heart disease: the Barilla factory revisited.Metabolism. 1999; 48: 989-994Abstract Full Text PDF PubMed Scopus (172) Google Scholar). The sensitivity and specificity of the TG/HDL-C ratio and the MetS to identify insulin resistance were calculated using as cut-points the values that separated the upper 25% of the TG/HDL-C ratio or a diagnosis of the MetS. Criteria for diagnosing the MetS are those outlined in the “harmonized” version of the ATP III and IDF, in which at least three of the following five criteria must be satisfied (8Alberti K.G. Eckel R.H. Grundy S.M. Zimmet P.Z. Cleeman J.I. Donato K.A. Fruchart J.C. James W.P. Loria C.M. Smith Jr, S.C. et al.Harmonizing the metabolic syndrome: a joint interim statement of the international diabetes federation task force on epidemiology and prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; International Association for the Study of Obesity.Circulation. 2009; 120: 1640-1645Crossref PubMed Scopus (9986) Google Scholar): 1) WC ≥ 90 cm in men and ≥ 80 cm in women; 2) HDL-C < 40 mg/dl in men and < 50 mg/dl in women; 3) TG ≥ 150 mg/dl; 4) SBP ≥ 130 mmHg or DBP ≥ 85 mmHg; 5) glucose ≥ 100 mg/dl and < 126 mg/dl. The mean and SD were calculated separately in women and men for each experimental variable measured, and Student's t test was used to compare cardiometabolic risk factors. A cardiometabolic risk profile was generated by calculating the mean and SD of each measurement, dividing the men and women into two groups, stratified into those whose TG/HDL-C concentration ratio was in the upper quartile versus the lower 75%, and those who did or did not meet diagnostic criteria for the MetS. The sensitivity and specificity (14Akobeng A.K. Understanding diagnostic tests specificity and 96: PubMed Scopus Google Scholar) with which either the TG/HDL-C ratio or the MetS identified the 25% of the population who were insulin resistant, as defined by HOMA-IR and were determined M.R. Carbajal H.A. Espeche W.G. C.E. E. Dulbecco C.A. Aizpurúa M. Marillet A.G. Reaven G.M. among the plasma triglyceride/high-density lipoprotein cholesterol concentration insulin resistance, and associated cardio-metabolic risk factors in men and J. Cardiol. 2012; Full Text Full Text PDF PubMed Scopus Google Scholar). Student's t test was performed using the A and for for Scholar). and metabolic of the study population are presented in that risk was in also provides an of the prevalence of cardiometabolic risk factors in this young approximately were by the of was in the Blood pressure was higher in the as was the prevalence of glucose ≥ 100 diabetes was to three men and one The most were high TG and low HDL-C the in men and the in and metabolic of the study of with ≥ WC 80 cm 90 cm SBP ≥ 130 mmHg; DBP ≥ 85 mmHg; mg/dl; TG ≥ 150 mg/dl; HDL-C < 50 mg/dl < 40 mg/dl ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± are as mean ± values are for independent ≥ WC 80 cm 90 cm SBP ≥ 130 mmHg; DBP ≥ 85 mmHg; mg/dl; TG ≥ 150 mg/dl; HDL-C < 50 mg/dl < 40 mg/dl in a Data are as mean ± values are for independent The TG/HDL-C concentration ratios that the of the 25% of the participants with the highest ratios were ≥ and ≥ in women and these TG/HDL-C concentration ratios of ≥ 3.5 and ≥ were as presents the prevalence of IR in women and men who have either an TG/HDL-C or the MetS. using HOMA-IR as the of insulin the of IR was greater in women who were identified by an TG/HDL-C ratio the MetS The results in men were versus The results were essentially QUICKI was used as the of IR. IR was more identified with the TG/HDL-C ratio with MetS of which of insulin resistance was of insulin resistance as identified by the TG/HDL-C ratio or low women, 3.5 for TG/HDL-C high women, 3.5 HOMA-IR women, QUICKI women, for HOMA-IR women, QUICKI women, in a low women, 3.5 for TG/HDL-C high women, 3.5 HOMA-IR women, QUICKI women, for HOMA-IR women, QUICKI women, A more analysis of the ability of the two different criteria to identify insulin-resistant individuals is shown in In women, the sensitivity of the TG/HDL-C ratio was greater in insulin-resistant individuals was the whereas the MetS greater The same observation in with the TG/HDL-C ratio greater sensitivity but These findings were of the of HOMA-IR or QUICKI as the of insulin and specificity with which TG/HDL-C ratio and MetS identify IR determined with resistance defined as HOMA-IR women and HOMA-IR ratio women; TG/HDL-C ratio 3.5 determined with resistance defined as QUICKI women and QUICKI ratio women; TG/HDL-C ratio 3.5 resistance defined as HOMA-IR women and HOMA-IR resistance defined as QUICKI women and QUICKI in a and 5 compare the cardiometabolic risk of identified they an TG/HDL-C versus those with a normal as as those with and the MetS. on the TG/HDL-C with the of age, of the risk factors measured were in those women 4) or men 5) with an results were seen the cardiometabolic risk factors of those identified as the of a diagnosis of the were compared with those the MetS risk profile in with ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± by the TG/HDL-C ratio versus MetS. < in a risk profile in with ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± by the TG/HDL-C ratio versus MetS. < < in a by the TG/HDL-C ratio versus MetS. < by the TG/HDL-C ratio versus MetS. < < In this an TG/HDL-C ratio was more the MetS in both women versus and men versus the of the between individuals with the MetS compared with those who did not meet the diagnostic criteria was greater the between those with an or normal TG/HDL-C a number of women with an TG/HDL-C ratio also the MetS of as did men of it did not to to the of these in cardiometabolic risk as a function of which criteria was used to identify the the it to to these is also of to that relatively women and men with a normal TG/HDL-C ratio the MetS. be from the results of this study. the data are with findings M.R. Carbajal H.A. Espeche W.G. C.E. E. Dulbecco C.A. Aizpurúa M. Marillet A.G. Reaven G.M. among the plasma triglyceride/high-density lipoprotein cholesterol concentration insulin resistance, and associated cardio-metabolic risk factors in men and J. Cardiol. 2012; Full Text Full Text PDF PubMed Scopus Google Scholar) that that the cut-points that separated the 25% individuals with the highest TG/HDL-C concentration ratio from the of the population were different in women in Second, and the cut-points that identified the 25% of the women and men with the highest TG/HDL-C concentration ratios in this study were essentially to those in a group of age men and women M.R. Carbajal H.A. Espeche W.G. C.E. E. Dulbecco C.A. Aizpurúa M. Marillet A.G. Reaven G.M. among the plasma triglyceride/high-density lipoprotein cholesterol concentration insulin resistance, and associated cardio-metabolic risk factors in men and J. Cardiol. 2012; Full Text Full Text PDF PubMed Scopus Google Scholar). in to being the TG/HDL-C cut-points obtained in this study were in a population of Mexican Mestizo compared with a population with M.R. Carbajal H.A. Espeche W.G. C.E. E. Dulbecco C.A. Aizpurúa M. Marillet A.G. Reaven G.M. among the plasma triglyceride/high-density lipoprotein cholesterol concentration insulin resistance, and associated cardio-metabolic risk factors in men and J. Cardiol. 2012; Full Text Full Text PDF PubMed Scopus Google Scholar). This is of in that the association of the TG/HDL-C ratio with fasting plasma insulin concentration was in and C. Ford E.S. Meng Y.X. Mokdad A.H. Reaven G.M. Does the association of the triglyceride to high-density lipoprotein cholesterol ratio with fasting serum insulin differ by race/ethnicity?.Cardiovasc. Diabetol. 2008; 7: 4Crossref PubMed Scopus (163) Google Scholar). the TG/HDL-C ratio has been associated with IR in and be used with risk factors to identify at increased risk of the of C. S. G. D. M. R. The cholesterol Association with insulin resistance in of different 2011; PubMed Scopus Google Scholar). the the of the results of this study is not as to a the being the sensitivity and specificity with which the TG/HDL-C ratio and the MetS identified insulin-resistant young individuals of was to values found in of men and women of (2Salazar M.R. Carbajal H.A. Espeche W.G. Dulbecco C.A. Aizpurúa M. Marillet A.G. Echeverría R.F. Reaven G.M. Relationships among insulin resistance, obesity, diagnosis of the metabolic syndrome and cardio-metabolic risk.Diab. Vasc. Dis. Res. 2011; 8: 109-116Crossref PubMed Scopus (50) Google Scholar, M.R. Carbajal H.A. Espeche W.G. C.E. E. Dulbecco C.A. Aizpurúa M. Marillet A.G. Reaven G.M. among the plasma triglyceride/high-density lipoprotein cholesterol concentration insulin resistance, and associated cardio-metabolic risk factors in men and J. Cardiol. 2012; Full Text Full Text PDF PubMed Scopus Google Scholar, Abbasi F. Lamendola C. T. Reaven G.M. Ford E.S. to insulin resistance of the III diagnostic criteria for of the metabolic PubMed Scopus Google Scholar, J. Turner between the III criteria for metabolic syndrome and insulin 2006; PubMed Scopus Google Scholar). the TG/HDL-C ratio nor the MetS criteria identify IR individuals with but both the sensitivity and specificity of the two approaches to identify insulin-resistant individuals are of the TG/HDL-C a the MetS the goal was to the number of IR individuals to be However, of the cardiometabolic risk profile is the the MetS to this task more in this group of young college both approaches that the cardiometabolic risk profile was in the 25% with the highest TG/HDL-C ratio or the the results in 5 suggest that the of between the group and the was identified by the MetS. The of this study are for the the utility of the TG/HDL-C ratio to identify apparently healthy individuals who are insulin resistant and at cardiometabolic risk was in students of a population of ancestry. In the findings were obtained from a population The is the of any However, these that our results are of in that values of the TG/HDL-C ratio separating the 25% of men and women with the highest ratios from the of the experimental population were essentially to those in men and women (2Salazar M.R. Carbajal H.A. Espeche W.G. Dulbecco C.A. Aizpurúa M. Marillet A.G. Echeverría R.F. Reaven G.M. Relationships among insulin resistance, obesity, diagnosis of the metabolic syndrome and cardio-metabolic risk.Diab. Vasc. Dis. Res. 2011; 8: 109-116Crossref PubMed Scopus (50) Google Scholar, M.R. Carbajal H.A. Espeche W.G. C.E. E. Dulbecco C.A. Aizpurúa M. Marillet A.G. Reaven G.M. among the plasma triglyceride/high-density lipoprotein cholesterol concentration insulin resistance, and associated cardio-metabolic risk factors in men and J. Cardiol. 2012; Full Text Full Text PDF PubMed Scopus Google Scholar, Abbasi F. Lamendola C. T. Reaven G.M. Ford E.S. to insulin resistance of the III diagnostic criteria for of the metabolic PubMed Scopus Google Scholar, J. Turner between the III criteria for metabolic syndrome and insulin 2006; PubMed Scopus Google Scholar). this was the the racial/ethnic versus in this study compared with the TG/HDL-C cut-points and a diagnosis of MetS were to identify IR whose associated cardiometabolic risk profile was more adverse the of the However, the two approaches in that the TG/HDL-C ratio identified a greater number of subjects, with findings in C. S. G. D. M. R. The cholesterol Association with insulin resistance in of different 2011; PubMed Scopus Google Scholar), whereas the MetS criteria to a group whose cardiometabolic risk profile was somewhat accentuated. In conclusion, the results of this study that TG/HDL-C cut-points based on findings in men and women of identify apparently healthy individuals who are insulin resistant and at increased cardiometabolic risk. In data were presented the of the TG/HDL-C ratio and the MetS to these this the the approach that most to their The are to CARPERMOR, S.A. de C.V., Universidad Autónoma de la Ciudad de México L. and body mass index diastolic blood pressure fasting plasma insulin homeostasis model assessment - insulin resistance insulin resistant metabolic syndrome quantitative insulin sensitivity check index systolic blood pressure triglyceride circumference