Background Prospective studies suggest that hyperinsulinemiamay be an important risk factor for ischemic heart disease.However, it has not been determined whether plasma insulin levelsare independently related to ischemic heart disease after adjustmentfor other risk factors, including plasma lipoprotein levels.
Methods In 1985 we collected blood samples from 2103 men fromsuburbs of Quebec City, Canada, who were 45 to 76 years of ageand who did not have ischemic heart disease. A first ischemicevent (angina pectoris, acute myocardial infarction, or deathfrom coronary heart disease) occurred in 114 men (case patients)between 1985 and 1990. Each case patient was matched for age,body-mass index, smoking habits, and alcohol consumption witha control selected from among the 1989 men who remained freeof ischemic heart disease during follow-up. After excludingmen with diabetes, we compared fasting plasma insulin and lipoproteinconcentrations at base line in 91 case patients and 105 controls.
Results Fasting insulin concentrations at base line were 18percent higher in the case patients than in the controls (P<0.001).Logistic-regression analysis showed that the insulin concentrationremained associated with ischemic heart disease (odds ratiofor ischemic heart disease with each increase of 1 SD in theinsulin concentration, 1.7; 95 percent confidence interval,1.3 to 2.4) after adjustment for systolic blood pressure, useof medications, and family history of ischemic heart disease.Further adjustment by multivariate analysis for plasma triglyceride,apolipoprotein B, low-density lipoprotein cholesterol, and high-densitylipoprotein cholesterol concentrations did not significantlydiminish the association between the insulin concentration andthe risk of ischemic heart disease (odds ratio, 1.6; 95 percentconfidence interval, 1.1 to 2.3).
Conclusions High fasting insulin concentrations appear to bean independent predictor of ischemic heart disease in men.
Insulin resistance and hyperinsulinemia are conditions knownto be associated with hypertriglyceridemia and low high-densitylipoprotein (HDL) cholesterol concentrations.1,2 Four prospectivestudies, in which fasting plasma insulin concentrations wereused as an index of insulin sensitivity, found that elevatedinsulin levels are associated with an increased risk of ischemicheart disease in men,3,4,5,6 but this finding has not been confirmedin all studies.7
Whether the relation between hyperinsulinemia and ischemic heartdisease is independent of related risk factors, such as hypertriglyceridemia,low HDL cholesterol concentrations, and hypertension, is notclear, however. Fontbonne and colleagues8,9,10 reported thathyperinsulinemia was not associated with an increased risk ofischemic heart disease unless accompanied by elevated plasmatriglyceride concentrations. Results from the Caerphilly prospectivestudy also suggested that the risk associated with hyperinsulinemiawas not independent of concomitant variations in triglycerideconcentrations.6 We examined this issue by measuring fastingplasma insulin levels in men with no evidence of ischemic heartdisease at study entry, in some of whom ischemic heart diseasedeveloped during the subsequent five years. The men with ischemicheart disease were compared with a group of matched controlswho remained free of such disease during the same period.
Methods
Study Cohort and Follow-Up
The Quebec Cardiovascular Study cohort has been described indetail previously.11,12 Briefly, 4637 men from 35 to 64 yearsof age, almost all of French Canadian descent, were recruitedin 1973 from seven counties in the Quebec City, Canada, metropolitanarea for a study of risk factors for cardiovascular disease,including nonfasting cholesterol concentrations. Men with clinicalevidence of ischemic heart disease at entry (n = 266) were excludedfrom further follow-up in the study. Subsequent evaluationswere carried out in 1974 and 1975, 1980, and 1985. From 1973through 1985, 371 men died. In 1985, further evaluation of riskfactors, including the fasting lipoprotein–lipid profile,was performed in 2443 (61 percent) of the remaining 4000 menscreened in 1973. Among the other 1557 men, 10 percent couldnot be located in 1985, 19 percent came to the clinic in a nonfastingstate, and 71 percent either declined to participate or wereevaluated in a nonfasting state at their homes by nurses participatingin the project.
In 1990 and 1991, all participants were contacted by mail andinvited to answer a short, standardized questionnaire coveringsmoking habits, use of medication, history of cardiovasculardisease, and diabetes mellitus. For those who reported suchdiseases and those who had died, all hospital charts were reviewed.For those who reported exertional angina and who were not hospitalized,a study cardiologist obtained the history to ascertain the characteristicsof the angina. Telephone calls were made to participants whodid not answer a second letter or, if this was unsuccessful,to a close family member.
Data on mortality were obtained for 99 percent of the entirecohort and data on morbidity for 96 percent. Analyses performedwith the 1973 data revealed that the age distribution of the2443 participants tested in 1985 was representative of the 1973cohort and that there was no significant difference in mortalitydue to ischemic heart disease between the 2443 participantsand the 1557 nonparticipants. Men who had ischemic heart diseasein 1985 (n = 253) were excluded; a complete risk-factor profilewas obtained for 2103 of the men who were free of ischemic heartdisease in 1985.12
Definition of Events
Criteria for the diagnosis of a first ischemic event includedexertional angina, coronary insufficiency,13 nonfatal myocardialinfarction, and death from coronary disease,14 as previouslydescribed.11,12 Confirmation of myocardial infarction requireddiagnostic electrocardiographic changes or two of the threefollowing criteria: the presence of symptoms, elevations incardiac-enzyme levels, or ischemic electrocardiographic changes.The diagnosis of exertional angina was based on typical symptomsof retrosternal squeezing or pressure-type discomfort occurringon exertion and relieved by rest, nitroglycerin, or both. Coronaryinsufficiency was defined as typical retrosternal chest painlasting at least 15 minutes and associated with transient ischemicchanges on the electrocardiogram (Minnesota code 5-1 or 5-2),but without elevation in the level of creatine kinase. All electrocardiogramswere interpreted by the same cardiologist, who was unaware ofthe participants' risk profile. Criteria for classifying a deathas due to coronary disease included confirmation of the diagnosison the death certificate or an autopsy report confirming thepresence of coronary disease and the absence of noncardiac diseasethat could explain death. Myocardial infarction was consideredfatal if death occurred within four weeks after the event orif myocardial infarction was diagnosed at autopsy. Myocardialinfarction and death related to ischemic heart disease wereconfirmed by data from the Provincial Death Registry. Informedconsent was obtained from the subjects to review the relevanthospital files. Autopsies were performed in about a third ofthe patients who died.
Evaluation of Risk Factors
In 1985, data on demographic and lifestyle variables, medicalhistory, and medication use were obtained by means of a standardizedquestionnaire administered by trained nurses and further reviewedby a physician. Each subject's weight and height were recorded.Resting blood pressure was measured after a five-minute restwith the patient sitting up; phase I and phase V of the Korotkoffsounds were used to measure systolic and diastolic blood pressure,respectively. The mean of two blood-pressure measurements obtainedfive minutes apart was used in the analyses. Information compiledfrom the questionnaire included family and personal historyof diabetes, smoking habits, alcohol consumption, and use ofmedications. The use of hypolipidemic drugs was not very commonin 1985; about 1 percent of the cohort received such therapy.The men in whom ischemic heart disease developed during follow-upwere more likely than those who remained free of ischemic heartdisease to use beta-blockers (11 percent vs. 6.5 percent) anddiuretics (7.5 percent vs. 2.8 percent). Alcohol intake wascomputed from the number of ounces of each type of beverage(beer, wine, or spirits) consumed per week and then standardizedas an absolute quantity of alcohol (1 oz = 22.5 g).15 Men wereclassified as having a family history of ischemic heart diseaseif they had at least one parent or sibling with a history ofischemic heart disease.
Matching Procedures
Of the initial sample of 2103 men who were free of clinicalsigns of ischemic heart disease in 1985, ischemic heart diseasedeveloped in 114 during five years of follow-up, which endedin September 1990.12 Each subject with confirmed ischemic heartdisease (case patient) was matched with a control subject selectedfrom among the 1989 men who had no clinical evidence of ischemicheart disease during follow-up. Subjects were matched on thebasis of age, cigarette smoking, body-mass index (the weightin kilograms divided by the square of the height in meters),and weekly alcohol intake. The mean differences in matched case–controlpairs were 0.6 year for age, 0.2 for body-mass index, and 0.2oz (4.5 g) per week for alcohol intake. The mean differencewithin pairs of cigarette smokers was 0.3 cigarette per day;all nonsmokers were matched with nonsmokers. Eight men wereexcluded from the analysis either because they had such highvalues for the number of cigarettes smoked per day that no matchedcontrol was available or because they had missing values forthe insulin concentration. Men who reported having diabetesmellitus or who were receiving hypoglycemic therapy at the base-lineevaluation (15 case patients and 1 control) were also excluded.
Laboratory Analyses
After the subjects had fasted for 12 hours, blood samples wereobtained from an antecubital vein while the subjects were sitting.A tourniquet was used but released before the withdrawal ofblood into Vacutainer tubes (Becton Dickinson, Mountain View,Calif.) containing EDTA. Plasma was separated from blood cellsby centrifugation and immediately used for measurement of lipidsand apolipoprotein B. Aliquots of fasting plasma were frozenat the time of collection for the subsequent assessment of insulinlevels. Plasma cholesterol and triglyceride concentrations weredetermined with an AutoAnalyzer II (Technicon Instruments, Tarrytown,N.Y.), as previously described.16 HDL cholesterol was measuredin the supernatant after precipitation of apolipoprotein B–containinglipoproteins with heparin–manganese chloride.17 Low-densitylipoprotein (LDL) cholesterol concentrations were estimatedwith the equation of Friedewald et al.18 for men with triglycerideconcentrations below 400 mg per deciliter (4.5 mmol per liter).Plasma apolipoprotein B concentrations were measured by therocket-immunoelectrophoresis method of Laurell,19 as describedpreviously.16 Serum standards for the apolipoprotein assay wereprepared in our laboratory and calibrated against serum samplesfrom the Centers for Disease Control and Prevention. The standardswere lyophilized and stored at -85°C until use. Peak heightsbetween 15 and 35 mm yielded linear and reliable results. Thecoefficients of variation for cholesterol, HDL cholesterol,triglyceride, and apolipoprotein measurements were all lessthan 3 percent.
Fasting insulin concentrations were measured with a commercialdouble-antibody radioimmunoassay (human-insulin–specificradioimmunoassay method, LINCO Research, St. Louis). In thisassay insulin shows little cross-reactivity (<0.2 percent)with human proinsulin.20 The coefficients of variation were3.5 percent for lower insulin concentrations (8 to 25 µUper milliliter [50 to 150 pmol per liter]), and 5.2 percentfor higher concentrations (33 to 83 µU per milliliter[200 to 500 pmol per liter]).
Statistical Analysis
Student's t-tests were used to compare mean values at base linein men in whom ischemic heart disease developed with those inthe men who remained free of such disease during the five-yearfollow-up. Differences in frequency were tested by chi-squareanalysis. Associations among variables were assessed with thePearson and Spearman correlation coefficients for parametricand nonparametric variables, respectively. Preliminary analysesshowed that the relation between metabolic risk factors andischemic heart disease was linear across their distribution.Logistic-regression analyses were therefore performed with plasmalipid, lipoprotein, and apolipoprotein concentrations includedas continuous variables.
Odds ratios for ischemic heart disease were computed as thechange in the risk of disease associated with an increase of1 SD in the concentration of the substance in question, accordingto unconditional logistic-regression analysis. Odds were adjustedfor the confounding effects of systolic blood pressure, useof medications, and family history of ischemic heart disease.
The study design eliminated the association between age, smoking,obesity, and alcohol intake, on the one hand, and the risk ofischemic heart disease, on the other. Inclusion of these variablesin the logistic models had no effect on the estimates of theassociation between other risk factors and ischemic heart disease.In addition, the use of conditional logistic regression, whichtakes into consideration the potentially confounding effectsof the variables used to match case patients and controls, yieldedresults that were essentially the same as those of the unconditionalregression analyses (data not shown).
For these reasons, variables used in the matching procedurewere not included in the analyses. Multiplicative terms of interactionwere also used to assess the potential interactions betweenfasting insulin concentrations and lipid, lipoprotein, and apolipoproteinconcentrations in relation to the risk of ischemic heart disease.All statistical tests were performed with the SAS software package(SAS Institute, Cary, N.C.).
Results
In the overall sample of 2103 men who were free of ischemicheart disease at study entry, the prevalence of diabetes mellituswas higher among the men in whom ischemic heart disease subsequentlydeveloped than among those who remained free of ischemic heartdisease (16 percent vs. 4 percent, P<0.001). After the exclusionof patients with diabetes from the matched analysis, the 91nondiabetic men in whom ischemic heart disease developed alsohad higher base-line plasma total cholesterol, LDL cholesterol,triglyceride, and apolipoprotein B concentrations than the 105matched controls who remained free of disease (Table 1). A significantdifference in the insulin concentration in fasting subjectswas observed between case patients and controls. Men in whomischemic heart disease developed had base-line insulin levelswhile fasting that were 18 percent higher than those of menwho had no ischemic heart disease (P<0.001). The ratio oftotal cholesterol to HDL cholesterol was also markedly higher(18 percent higher) among the men who subsequently had ischemicheart disease.
Table 1. Base-Line Characteristics of 91 Men with Clinical Manifestations of Ischemic Heart Disease (Case Patients) and 105 Matched Controls from the Quebec Cardiovascular Study.
We investigated the association between the insulin concentrationand the risk of ischemic heart disease, both before and afteradjustment for plasma lipid and apolipoprotein concentrations,using multiple logistic-regression analysis (Table 2). Higherplasma concentrations of insulin were associated with a significantincrease in the risk of ischemic heart disease (odds ratio forischemic heart disease with each increase of 1 SD in the insulinconcentration, 1.7; 95 percent confidence interval, 1.3 to 2.4);this association was independent of systolic blood pressure,medication use, and family history of ischemic heart disease.The odds ratio for ischemic heart disease in patients with higherinsulin concentrations after fasting was essentially unchangedwhen the variables used in matching (age, body-mass index, smokingstatus, and alcohol consumption) were included in the logisticmodel (odds ratio, 2.1; 95 percent confidence interval, 1.4to 3.0). Further adjustment for the potentially confoundingeffects of the triglyceride, LDL cholesterol, HDL cholesterol,and apolipoprotein B concentrations (models 2 through 6 in Table 2)did not substantially weaken the relation between insulinand the risk of ischemic heart disease. Accordingly, the associationbetween the concentrations of LDL cholesterol, triglycerides,and apolipoprotein B and the total:HDL cholesterol ratio, onthe one hand, and the risk of ischemic heart disease, on theother, remained significant after adjustment for insulin levels.Finally, the relation between plasma insulin concentrationsand the risk of ischemic heart disease was not altered significantlywhen the additive contribution of the triglyceride, HDL cholesterol,and apolipoprotein B concentrations to risk was accounted for(model 7); this finding suggests that the increased risk ofischemic heart disease associated with hyperinsulinemia wasat least partly independent of variations in plasma lipoproteinconcentrations.
Table 2. Relation between Insulin Concentrations at Base Line in Fasting Subjects and the Subsequent Development of Ischemic Heart Disease, before and after Adjustment for Plasma Lipid and Apolipoprotein B Levels, from Seven Models in the Multivariate Logistic Analysis.
The potential interaction between hyperinsulinemia and plasmalipoproteins was tested by subdividing the sample into thirdsaccording to insulin concentration and either low or high triglyceridelevels, apolipoprotein B levels, and total:HDL cholesterol ratios.The results, presented in Figure 1, indicate that the risk ofischemic heart disease associated with hyperinsulinemia didnot appear to be further increased in the presence of elevatedtriglyceride levels (odds ratios for insulin concentrations>15 µU per milliliter [>92 pmol per liter], 5.3in men with triglyceride concentrations below the 50th percentileand 6.7 in men with concentrations at or above the 50th percentile,as compared with the reference group; P<0.001]). Among menwith an elevated total:HDL cholesterol ratio (i.e., one at orabove the 50th percentile), those with high or intermediateinsulin concentrations (>12 µU per milliliter) hadthe greatest increase in risk. Furthermore, men with high plasmainsulin concentrations but with a total:HDL cholesterol ratiobelow 6 (the 50th percentile) were also at greater risk forischemic heart disease than men in the lowest third of the samplewith respect to insulin (odds ratio, 7.1; P= 0.001). Elevatedplasma insulin concentrations were also associated with an increasedrisk of ischemic heart disease among men with low apolipoproteinB concentrations (odds ratio, 3.2; P = 0.04). However, the mostsubstantial increase in the risk of ischemic heart disease wasobserved among men with elevated concentrations of both insulinand apolipoprotein B (odds ratio, 11.0; P<0.001). Althougha test for multiplicative interaction between apolipoproteinB and insulin did not indicate significance (P = 0.2), the absoluteeffect of hyperinsulinemia on ischemic heart disease appearedto depend largely on the apolipoprotein B concentration.
Figure 1. Odds Ratios for Ischemic Heart Disease According to Plasma Insulin and Triglyceride Concentrations, Total:HDL Cholesterol Ratios, and Apolipoprotein B Concentrations.
Insulin was measured after subjects had fasted for 12 hours. The median triglyceride concentration (150 mg per deciliter [1.7 mmol per liter]), total:HDL cholesterol ratio (6.0), and apolipoprotein B concentration (119 mg per deciliter) were used to define men with either low levels (below the 50th percentile) or high levels (at or above the 50th percentile) for these variables. The results of tests for multiplicative interactions did not reach significance at the 0.05 level for any of the combinations. P values are for comparisons with the reference group, which was assigned an odds ratio of 1.0. To convert values for insulin to picomoles per liter, multiply by 6.
Although statistically significant, the associations betweenplasma insulin concentrations in fasting subjects and body-massindex (r = 0.41, P<0.001), triglyceride concentrations (r= 0.23, P = 0.001), apolipoprotein B concentrations (r = 0.16,P = 0.02), HDL cholesterol concentrations (r = -0.28, P<0.001)and the total:HDL cholesterol ratio (r = 0.25, P<0.001) wereof only moderate magnitude; these findings therefore providefurther support for the concept that the risk of ischemic heartdisease associated with hyperinsulinemia appears to be largelyindependent of variations in plasma lipoprotein concentrations.No association was found between plasma insulin concentrationsand systolic or diastolic blood pressure.
Discussion
Our results agree with those of previous prospective investigations,which have found that a high plasma insulin concentration infasting subjects is associated with an increased incidence ofischemic heart disease in nondiabetic men.2,3,4,5,6 The mechanismsresponsible for this association, however, remain speculative.It had been suggested that the risk associated with hyperinsulinemiawas largely explained by the lipid abnormalities that are commonamong men with elevated insulin concentrations.6,8,9,10,21,22Although we found significant associations between insulin levelsin fasting subjects and lipoprotein concentrations, furtheranalyses revealed that the risk of ischemic heart disease relatedto hyperinsulinemia was largely independent of the concomitantdyslipidemic state. A synergistic effect was noted, however,since the combination of hyperinsulinemia and elevated apolipoproteinB concentrations or an increased total:HDL cholesterol ratiosubstantially increased the risk of ischemic heart disease inmen who had both these metabolic alterations.
These results support the notion that hyperinsulinemia may increasethe risk of ischemic heart disease through alterations in metabolicprocesses other than the related dyslipidemia. In this regard,it has been reported that plasma concentrations of plasminogen-activatorinhibitor type 1 are increased in patients with hyperinsulinemicinsulin resistance,23 an alteration that may impair fibrinolysisand increase susceptibility to thrombosis in men with hyperinsulinemia.Furthermore, the concomitant elevation of blood pressure mayalso be a contributing factor,24 although the association betweenhyperinsulinemia and ischemic heart disease in our study wasunchanged by adjustment for blood pressure.
On the other hand, it has been suggested that hyperinsulinemiain persons without diabetes may be a marker for a cluster ofmetabolic abnormalities, including hypertension, dyslipidemia,impaired fibrinolysis, and impaired insulin-mediated glucoseuptake.1 The concept of the insulin-resistance syndrome hasevolved considerably since its introduction by Reaven in 1988,1and it has been suggested that visceral obesity may also bea common component of the cluster of metabolic abnormalitiesfound in insulin-resistant subjects.25,26 We have shown thatpersons in whom overweight is characterized by the accumulationof only small amounts of visceral adipose tissue, as measuredby computed tomography, did not differ substantially from normal-weightcontrols in terms of risk factors for cardiovascular disease.27,28,29Overweight patients in whom there was a large amount of visceraladipose tissue were, on the other hand, characterized by a clusterof metabolic disturbances that included glucose intolerance,hyperinsulinemia, hypertriglyceridemia, elevated apolipoproteinB concentrations, abnormally low HDL cholesterol concentrations,and an elevated total:HDL cholesterol ratio.27,29 Analyses ofthe Paris Prospective Study cohort suggested that the abdomen-to-thighratio, a crude anthropometric estimate of upper-body fat, wasan independent predictor of the risk of death from ischemicheart disease, whereas the insulin concentration in fastingsubjects was no longer independently associated with ischemicheart disease after this variable was controlled for.30 Althoughadditional work is clearly warranted to clarify this issue,the results of our study suggest that the relation of hyperinsulinemiato ischemic heart disease may be largely independent of alterationsin body weight, blood pressure, and plasma lipoprotein concentrations.
The presence of hyperinsulinemia in fasting subjects may thereforeserve as a crude but clinically relevant marker for other metabolicand hemostatic disturbances — namely, visceral obesity,a procoagulant state, and alterations in growth factor levels— all of which are associated with an increased risk ofischemic heart disease.31 However, laboratory standardizationof insulin measurements remains a problem, and there is currentlyno universally accepted criterion for hyperinsulinemia in thefasting state. We believe that it is relevant to raise thisissue, since we used a radioimmunoassay that did not cross-reactwith pro-insulin32; this was not the case in previous prospectivestudies, in which insulin could not be identified as an independentpredictor of ischemic heart disease after adjustment for otherrisk factors. Since an insulin-resistant, hyperinsulinemic stateincreases the risk of type II diabetes mellitus,33 our resultsalso support the notion that maintaining an adequate level ofinsulin sensitivity and low plasma insulin concentrations throughproper diet and exercise habits not only may be of value inpreventing type II diabetes, but also may reduce the risk ofheart disease.
Supported by the National Health Research Development Program,Health and Welfare Canada, by the Heart and Stroke Foundationof Canada, and by Fournier Pharma, Inc. Mr. Lamarche is therecipient of a fellowship from the Medical Research Councilof Canada.
We are indebted to Mr. Paul-Marie Bernard, M.Sc., for his experthelp with the statistical analyses; to Dr. N. Michelle Robitaillefor her important support in the collection of the data; toMiss Louise Fleury and Mr. André Tchernof; and to the4637 participants in the Quebec Cardiovascular Study, whosecooperation made this study possible.
Source Information
From the Lipid Research Center, Laval University Hospital Research Center, Quebec (J.-P.D., B.L., P.M., B.C., S.M., P.-J.L.); and the Department of Medicine, University of Montreal, Montreal (G.R.D.) — both in Canada.
Address reprint requests to Dr. Després at the Lipid Research Center, CHUL Research Center, 2705 Laurier Blvd., Ste.-Foy, QC G1V 4G2, Canada.
References
Reaven GM. Role of insulin resistance in human disease. Diabetes 1988;37:1595-1607. [Abstract]
Laws A, Reaven GM. Evidence for an independent relationship between insulin resistance and fasting plasma HDL-cholesterol, triglyceride and insulin concentrations. J Intern Med 1992;231:25-30. [Medline]
Pyörälä K. Relationship of glucose tolerance and plasma insulin to the incidence of coronary heart disease: results from two population studies in Finland. Diabetes Care 1979;2:131-141. [Abstract]
Welborn TA, Wearne K. Coronary heart disease incidence and cardiovascular mortality in Busselton with reference to glucose and insulin concentrations. Diabetes Care 1979;2:154-160. [Abstract]
Eschwège E, Richard JL, Thibult N, et al. Coronary heart disease mortality in relation with diabetes, blood glucose and plasma insulin levels: the Paris Prospective Study, ten years later. Horm Metab Res Suppl 1985;15:41-46. [Medline]
Yarnell JWG, Sweetnam PM, Marks V, Teale JD, Bolton CH. Insulin in ischaemic heart disease: are associations explained by triglyceride concentrations? The Caerphilly prospective study. Br Heart J 1994;171:293-296.
Wingard DL, Barrett-Connor EL, Ferrara A. Is insulin really a heart disease risk factor? Diabetes Care 1995;18:1299-1304. [Medline]
Fontbonne A. Why can high insulin levels indicate a risk for coronary heart disease? Diabetologia 1994;37:953-955. [Medline]
Fontbonne A, Eschwège E, Cambien F, et al. Hypertriglyceridaemia as a risk factor of coronary heart disease mortality in subjects with impaired glucose tolerance or diabetes: results from the 11-year follow-up of the Paris Prospective Study. Diabetologia 1989;32:300-304. [CrossRef][Medline]
Fontbonne A, Charles MA, Thibult N, et al. Hyperinsulinaemia as a predictor of coronary heart disease mortality in a healthy population: the Paris Prospective Study, 15-year follow-up. Diabetologia 1991;34:356-361. [CrossRef][Medline]
Dagenais GR, Robitaille NM, Lupien PJ, et al. First coronary heart disease event rates in relation to major risk factors: Québec Cardiovascular Study. Can J Cardiol 1990;6:274-280. [Medline]
Lamarche B, Després JP, Moorjani M, Cantin B, Dagenais GR, Lupien PJ. Prevalence of dyslipidemic phenotypes in ischemic heart disease (prospective results from the Québec Cardiovascular Study). Am J Cardiol 1995;75:1189-1195. [CrossRef][Medline]
Castelli WP, Garrison RJ, Wilson PWF, Abbott RD, Kalousdian S, Kannel WB. Incidence of coronary heart disease and lipoprotein cholesterol levels: the Framingham Study. JAMA 1986;256:2835-2838. [Free Full Text]
Gillum RF, Fortmann SP, Prineas RJ, Kottke TE. International diagnostic criteria for acute myocardial infarction and acute stroke. Am Heart J 1984;108:150-158. [CrossRef][Medline]
Marmot MG. Alcohol and coronary heart disease. Int J Epidemiol 1984;13:160-167. [Free Full Text]
Moorjani S, Dupont A, Labrie F, et al. Increase in plasma high-density lipoprotein concentration following complete androgen blockage in men with prostatic carcinoma. Metabolism 1987;36:244-250. [CrossRef][Medline]
Albers JJ, Warnick GR, Wiebe D, et al. Multi-laboratory comparison of three heparin Mn2+ precipitation procedures for estimating cholesterol in high-density lipoprotein. Clin Chem 1978;24:853-856. [Free Full Text]
Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 1972;18:499-502. [Abstract]
Morgan CR, Lazarow A. Immunoassay of insulin: two antibody system: plasma insulin levels in normal, subdiabetic and diabetic rats. Diabetes 1963;12:115-126.
Orchard TJ, Becker DJ, Bates M, Kuller LH, Drash AL. Plasma insulin and lipoprotein concentrations: an atherogenic association? Am J Epidemiol 1983;118:326-337. [Free Full Text]
Zavaroni I, Bonora E, Pagliara M, et al. Risk factors for coronary artery disease in healthy persons with hyperinsulinemia and normal glucose tolerance. N Engl J Med 1989;320:702-706. [Abstract]
Juhan-Vague I, Alessi MC, Vague P. Increased plasma plasminogen activator inhibitor 1 levels: a possible link between insulin resistance and atherothrombosis. Diabetologia 1991;34:457-462. [CrossRef][Medline]
Kaplan NM. The deadly quartet: upper-body obesity, glucose intolerance, hypertriglyceridemia, and hypertension. Arch Intern Med 1989;149:1514-1520. [Free Full Text]
Després JP, Moorjani S, Lupien PJ, Tremblay A, Nadeau A, Bouchard C. Regional distribution of body fat, plasma lipoproteins, and cardiovascular disease. Arteriosclerosis 1990;10:497-511. [Free Full Text]
Després JP. Dyslipidaemia and obesity. Baillieres Clin Endocrinol Metab 1994;8:629-660. [CrossRef][Medline]
Després JP, Nadeau A, Tremblay A, et al. Role of deep abdominal fat in the association between regional adipose tissue distribution and glucose tolerance in obese women. Diabetes 1989;38:304-309. [Abstract]
Després JP, Moorjani S, Perland M, et al. Adipose tissue distribution and plasma lipoprotein levels in obese women: importance of intra-abdominal fat. Arteriosclerosis 1989;9:203-210. [Free Full Text]
Pouliot MC, Després JP, Nadeau A, et al. Visceral obesity in men: associations with glucose tolerance, plasma insulin and lipoprotein levels. Diabetes 1992;41:826-834. [Abstract]
Casassus P, Fontbonne A, Thibult N, et al. Upper-body fat distribution: a hyperinsulinemia-independent predictor of coronary heart disease mortality: the Paris Prospective Study. Arterioscler Thromb 1992;12:1387-1392. [Free Full Text]
Bierman EL. Atherogenesis in diabetes. Arterioscler Thromb 1992;12:647-656. [Free Full Text]
Haffner SM, Mykkänen L, Stern MP, Valdez RA, Heisserman JA, Bowsher RR. Relationship of proinsulin and insulin to cardiovascular risk factors in nondiabetic subjects. Diabetes 1993;42:1297-1302. [Abstract]
Martin BC, Warram JH, Krolewski AS, Bergman RN, Soeldner JS, Kahn CR. Role of glucose and insulin resistance in development of type 2 diabetes mellitus: results of a 25-year follow-up study. Lancet 1992;340:925-929. [CrossRef][Medline]
Engberding, N., San Martin, A., Martin-Garrido, A., Koga, M., Pounkova, L., Lyons, E., Lassegue, B., Griendling, K. K.
(2009). Insulin-Like Growth Factor-1 Receptor Expression Masks the Antiinflammatory and Glucose Uptake Capacity of Insulin in Vascular Smooth Muscle Cells. Arterioscler. Thromb. Vasc. Bio.
29: 408-415
[Abstract][Full Text]
Dandona, P., Chaudhuri, A., Ghanim, H., Mohanty, P.
(2009). Insulin as an anti-inflammatory and antiatherogenic modulator.. J Am Coll Cardiol
53: S14-S20
[Abstract][Full Text]
Steinberger, J., Daniels, S. R., Eckel, R. H., Hayman, L., Lustig, R. H., McCrindle, B., Mietus-Snyder, M. L.
(2009). Progress and Challenges in Metabolic Syndrome in Children and Adolescents: A Scientific Statement From the American Heart Association Atherosclerosis, Hypertension, and Obesity in the Young Committee of the Council on Cardiovascular Disease in the Young; Council on Cardiovascular Nursing; and Council on Nutrition, Physical Activity, and Metabolism. Circulation
119: 628-647
[Full Text]
Efstathiou, J. A., Bae, K., Shipley, W. U., Hanks, G. E., Pilepich, M. V., Sandler, H. M., Smith, M. R.
(2009). Cardiovascular Mortality After Androgen Deprivation Therapy for Locally Advanced Prostate Cancer: RTOG 85-31. JCO
27: 92-99
[Abstract][Full Text]
Gong, Z., Huang, C., Sheng, X., Zhang, Y., Li, Q., Wang, M.-W., Peng, L., Zang, Y. Q.
(2009). The Role of Tanshinone IIA in the Treatment of Obesity through Peroxisome Proliferator-Activated Receptor {gamma} Antagonism. Endocrinology
150: 104-113
[Abstract][Full Text]
Goodarzi, M. O., Psaty, B. M.
(2008). Glucose Lowering to Control Macrovascular Disease in Type 2 Diabetes: Treating the Wrong Surrogate End Point?. JAMA
300: 2051-2053
[Full Text]
Higgins, P. B, Fernandez, J. R, Garvey, W T., Granger, W. M, Gower, B. A
(2008). Entero-insular axis and postprandial insulin differences in African American and European American children. Am. J. Clin. Nutr.
88: 1277-1283
[Abstract][Full Text]
Rossi, R., Nuzzo, A., Origliani, G., Modena, M. G.
(2008). Metabolic Syndrome Affects Cardiovascular Risk Profile and Response to Treatment in Hypertensive Postmenopausal Women. Hypertension
52: 865-872
[Abstract][Full Text]
Panoulas, V. F., Metsios, G. S., Pace, A. V., John, H., Treharne, G. J., Banks, M. J., Kitas, G. D.
(2008). Hypertension in rheumatoid arthritis. Rheumatology (Oxford)
47: 1286-1298
[Abstract][Full Text]
Kim, S. H., Reaven, G. M.
(2008). Insulin Resistance and Hyperinsulinemia: You can't have one without the other. Diabetes Care
31: 1433-1438
[Abstract][Full Text]
Sam, S., Coviello, A. D., Sung, Y.-A., Legro, R. S., Dunaif, A.
(2008). Metabolic Phenotype in the Brothers of Women with Polycystic Ovary Syndrome. Diabetes Care
31: 1237-1241
[Abstract][Full Text]
Russell, J. C., Proctor, S. D., Kelly, S. E., Brindley, D. N.
(2008). Pair feeding-mediated changes in metabolism: stress response and pathophysiology in insulin-resistant, atherosclerosis-prone JCR:LA-cp rats. Am. J. Physiol. Endocrinol. Metab.
294: E1078-E1087
[Abstract][Full Text]
Grossmann, M., Thomas, M. C., Panagiotopoulos, S., Sharpe, K., MacIsaac, R. J., Clarke, S., Zajac, J. D., Jerums, G.
(2008). Low Testosterone Levels Are Common and Associated with Insulin Resistance in Men with Diabetes. J. Clin. Endocrinol. Metab.
93: 1834-1840
[Abstract][Full Text]
Juutilainen, A., Lehto, S., Ronnemaa, T., Pyorala, K., Laakso, M.
(2008). Similarity of the Impact of Type 1 and Type 2 Diabetes on Cardiovascular Mortality in Middle-Aged Subjects. Diabetes Care
31: 714-719
[Abstract][Full Text]
Ashikaga, T., Nishizaki, M., Fujii, H., Ihara, K., Niki, S., Murai, T., Maeda, S., Yamawake, N., Kishi, Y., Isobe, M.
(2008). Coronary Endothelial Dysfunction and Impaired Microcirculation Response to Atrial Natriuretic Peptide in Hyperinsulinemia. J CARDIOVASC PHARMACOL THER
13: 58-63
[Abstract]
Duan, S. Z., Usher, M. G., Mortensen, R. M.
(2008). Peroxisome Proliferator-Activated Receptor-{gamma}-Mediated Effects in the Vasculature. Circ. Res.
102: 283-294
[Abstract][Full Text]
Lund, S. S, Tarnow, L., Frandsen, M., Smidt, U. M, Pedersen, O., Parving, H.-H., Vaag, A. A
(2008). Impact of metformin versus the prandial insulin secretagogue, repaglinide, on fasting and postprandial glucose and lipid responses in non-obese patients with type 2 diabetes. Eur J Endocrinol
158: 35-46
[Abstract][Full Text]
Naya, T., Hosomi, N., Ohyama, H., Ichihara, S.-I., Ban, C. R., Takahashi, T., Taminato, T., Feng, A., Kohno, M., Koziol, J. A.
(2008). Smoking, Fasting Serum Insulin, and Obesity Are the Predictors of Carotid Atherosclerosis in Relatively Young Subjects. ANGIOLOGY
58: 677-684
[Abstract]
Berglund, L., Lefevre, M., Ginsberg, H. N, Kris-Etherton, P. M, Elmer, P. J, Stewart, P. W, Ershow, A., Pearson, T. A, Dennis, B. H, Roheim, P. S, Ramakrishnan, R., Reed, R., Stewart, K., Phillips, K. M, for the DELTA Investigators,
(2007). Comparison of monounsaturated fat with carbohydrates as a replacement for saturated fat in subjects with a high metabolic risk profile: studies in the fasting and postprandial states. Am. J. Clin. Nutr.
86: 1611-1620
[Abstract][Full Text]
Harsch, I. A.
(2007). Metabolic disturbances in patients with obstructive sleep apnoea syndrome. ERR
16: 196-202
[Abstract][Full Text]
Air, E. L., Kissela, B. M.
(2007). Diabetes, the Metabolic Syndrome, and Ischemic Stroke: Epidemiology and possible mechanisms. Diabetes Care
30: 3131-3140
[Full Text]
Sarwar, N., Sattar, N., Gudnason, V., Danesh, J.
(2007). Circulating concentrations of insulin markers and coronary heart disease: a quantitative review of 19 Western prospective studies. Eur Heart J
28: 2491-2497
[Abstract][Full Text]
Schindler, C.
(2007). Review: The metabolic syndrome as an endocrine disease: is there an effective pharmacotherapeutic strategy optimally targeting the pathogenesis?. Ther Adv Cardiovasc Dis
1: 7-26
[Abstract]
Ivey, F. M., Ryan, A. S., Hafer-Macko, C. E., Goldberg, A. P., Macko, R. F.
(2007). Treadmill Aerobic Training Improves Glucose Tolerance and Indices of Insulin Sensitivity in Disabled Stroke Survivors: A Preliminary Report. Stroke
38: 2752-2758
[Abstract][Full Text]
Zornitzki, T., Ayzenberg, O., Gandelman, G., Vered, S., Yaskil, E., Faraggi, D., Caspi, A., Goland, S., Shvez, O., Schattner, A., Knobler, H.
(2007). Diabetes, but not the metabolic syndrome, predicts the severity and extent of coronary artery disease in women. QJM
100: 575-581
[Abstract][Full Text]
Colussi, G., Catena, C., Lapenna, R., Nadalini, E., Chiuch, A., Sechi, L. A.
(2007). Insulin Resistance and Hyperinsulinemia Are Related to Plasma Aldosterone Levels in Hypertensive Patients. Diabetes Care
30: 2349-2354
[Abstract][Full Text]
Donatelli, F., Vavassori, A., Bonfanti, S., Parrella, P., Lorini, L., Fumagalli, R., Carli, F.
(2007). Epidural Anesthesia and Analgesia Decrease the Postoperative Incidence of Insulin Resistance in Preoperative Insulin-Resistant Subjects Only. Anesth. Analg.
104: 1587-1593
[Abstract][Full Text]
McLaughlin, T., Abbasi, F., Lamendola, C., Reaven, G.
(2007). Heterogeneity in the Prevalence of Risk Factors for Cardiovascular Disease and Type 2 Diabetes Mellitus in Obese Individuals: Effect of Differences in Insulin Sensitivity. Arch Intern Med
167: 642-648
[Abstract][Full Text]
van Eijk, I C, Peters, M J L, Nurmohamed, M T, van Deutekom, A W, Dijkmans, B A C, Simsek, S
(2007). Decrease of fructosamine levels during treatment with adalimumab in patients with both diabetes and rheumatoid arthritis. Eur J Endocrinol
156: 291-293
[Abstract][Full Text]
Cardellini, M., Marini, M. A., Frontoni, S., Hribal, M. L., Andreozzi, F., Perticone, F., Federici, M., Lauro, D., Sesti, G.
(2007). Carotid artery intima-media thickness is associated with insulin-mediated glucose disposal in nondiabetic normotensive offspring of type 2 diabetic patients. Am. J. Physiol. Endocrinol. Metab.
292: E347-E352
[Abstract][Full Text]
Basili, S., Pacini, G., Guagnano, M. T., Manigrasso, M. R., Santilli, F., Pettinella, C., Ciabattoni, G., Patrono, C., Davi, G.
(2006). Insulin Resistance as a Determinant of Platelet Activation in Obese Women. J Am Coll Cardiol
48: 2531-2538
[Abstract][Full Text]
Paradis, M.-E., Badellino, K. O., Rader, D. J., Deshaies, Y., Couture, P., Archer, W. R., Bergeron, N., Lamarche, B.
(2006). Endothelial lipase is associated with inflammation in humans. J. Lipid Res.
47: 2808-2813
[Abstract][Full Text]
the Metascreen Writing Committee,
(2006). The Metabolic Syndrome Is a Risk Indicator of Microvascular and Macrovascular Complications in Diabetes: Results from Metascreen, a multicenter diabetes clinic-based survey. Diabetes Care
29: 2701-2707
[Abstract][Full Text]
Black, R. N. A., Spence, M., McMahon, R. O., Cuskelly, G. J., Ennis, C. N., McCance, D. R., Young, I. S., Bell, P. M., Hunter, S. J.
(2006). Effect of Eucaloric High- and Low-Sucrose Diets With Identical Macronutrient Profile on Insulin Resistance and Vascular Risk: A Randomized Controlled Trial. Diabetes
55: 3566-3572
[Abstract][Full Text]
Gigleux, I., Gagnon, J., St-Pierre, A., Cantin, B., Dagenais, G. R., Meyer, F., Despres, J.-P., Lamarche, B.
(2006). Moderate Alcohol Consumption Is More Cardioprotective in Men with the Metabolic Syndrome. J. Nutr.
136: 3027-3032
[Abstract][Full Text]
Asato, Y., Katsuren, K., Ohshiro, T., Kikawa, K., Shimabukuro, T., Ohta, T.
(2006). Relationship Between Lipid Abnormalities and Insulin Resistance in Japanese School Children. Arterioscler. Thromb. Vasc. Bio.
26: 2781-2786
[Abstract][Full Text]
McLaughlin, T., Carter, S., Lamendola, C., Abbasi, F., Yee, G., Schaaf, P., Basina, M., Reaven, G.
(2006). Effects of moderate variations in macronutrient composition on weight loss and reduction in cardiovascular disease risk in obese, insulin-resistant adults.. Am. J. Clin. Nutr.
84: 813-821
[Abstract][Full Text]
Gupta, N., Park, E., Sandhu, H., Goh, T., Tchipashvili, V., Giacca, A.
(2006). Direct and indirect effects of insulin on hepatic glucose production in diabetic depancreatized dogs during euglycemia.. J Endocrinol
190: 695-702
[Abstract][Full Text]
Kirby, M.
(2006). Heart failure and diabetes in primary care. British Journal of Diabetes & Vascular Disease
6: 220-228
[Abstract]
Paradis, M.-E., Badellino, K. O., Rader, D. J., Tchernof, A., Richard, C., Luu-The, V., Deshaies, Y., Bergeron, J., Archer, W. R., Couture, P., Bergeron, N., Lamarche, B.
(2006). Visceral Adiposity and Endothelial Lipase. J. Clin. Endocrinol. Metab.
91: 3538-3543
[Abstract][Full Text]
Catena, C., Lapenna, R., Baroselli, S., Nadalini, E., Colussi, G., Novello, M., Favret, G., Melis, A., Cavarape, A., Sechi, L. A.
(2006). Insulin Sensitivity in Patients with Primary Aldosteronism: A Follow-Up Study. J. Clin. Endocrinol. Metab.
91: 3457-3463
[Abstract][Full Text]
Malnick, S.D.H., Knobler, H.
(2006). The medical complications of obesity. QJM
99: 565-579
[Full Text]
Morse, C. G., Kovacs, J. A.
(2006). Metabolic and skeletal complications of HIV infection: the price of success.. JAMA
296: 844-854
[Abstract][Full Text]
Yoshii, H., Lam, T. K. T., Gupta, N., Goh, T., Haber, C. A., Uchino, H., Kim, T. T. Y., Chong, V. Z., Shah, K., Fantus, I. G., Mari, A., Kawamori, R., Giacca, A.
(2006). Effects of portal free fatty acid elevation on insulin clearance and hepatic glucose flux. Am. J. Physiol. Endocrinol. Metab.
290: E1089-E1097
[Abstract][Full Text]
Smith, M. R., Lee, H., Nathan, D. M.
(2006). Insulin Sensitivity during Combined Androgen Blockade for Prostate Cancer. J. Clin. Endocrinol. Metab.
91: 1305-1308
[Abstract][Full Text]
Proctor, S. D., Dreher, K. L., Kelly, S. E., Russell, J. C.
(2006). Hypersensitivity of Prediabetic JCR:LA-cp Rats to Fine Airborne Combustion Particle-Induced Direct and Noradrenergic-Mediated Vascular Contraction. Toxicol Sci
90: 385-391
[Abstract][Full Text]
Kowalska, I., Straczkowski, M., Nikolajuk, A., Krukowska, A., Kinalska, I., Gorska, M.
(2006). Plasma adiponectin concentration and tumor necrosis factor-{alpha} system activity in lean non-diabetic offspring of type 2 diabetic subjects. Eur J Endocrinol
154: 319-324
[Abstract][Full Text]
De Caterina, R., Zampolli, A., Del Turco, S., Madonna, R., Massaro, M.
(2006). Nutritional mechanisms that influence cardiovascular disease. Am. J. Clin. Nutr.
83: 421S-426S
[Abstract][Full Text]
Wittlin, S. D.
(2006). Treating the Spectrum of Type 2 Diabetes: Emphasis on Insulin Pump Therapy. The Diabetes Educator
32: 39S-46S
[Full Text]
Nishio, K., Sakurai, M., Kusuyama, T., Shigemitsu, M., Fukui, T., Kawamura, K., Itoh, S., Konno, N., Katagiri, T.
(2006). A Randomized Comparison of Pioglitazone to Inhibit Restenosis After Coronary Stenting in Patients With Type 2 Diabetes. Diabetes Care
29: 101-106
[Abstract][Full Text]
van Wijk, J. P.H., de Koning, E. J.P., Cabezas, M. C., op't Roodt, J., Joven, J., Rabelink, T. J., Hoepelman, A. I.
(2005). Comparison of Rosiglitazone and Metformin for Treating HIV Lipodystrophy: A Randomized Trial. ANN INTERN MED
143: 337-346
[Abstract][Full Text]
Kahn, R., Buse, J., Ferrannini, E., Stern, M.
(2005). The Metabolic Syndrome: Time for a Critical Appraisal: Joint statement from the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care
28: 2289-2304
[Abstract][Full Text]
Lindeman, R. D., Wayne, S. J., Baumgartner, R. N., Garry, P. J.
(2005). Cognitive Function in Drinkers Compared to Abstainers in The New Mexico Elder Health Survey. Journals of Gerontology Series A: Biological Sciences and Medical Sciences
60: 1065-1070
[Abstract][Full Text]
Kim, S. H., Abbasi, F., Chu, J. W., McLaughlin, T. L., Lamendola, C., Polonsky, K. S., Reaven, G. M.
(2005). Rosiglitazone Reduces Glucose-Stimulated Insulin Secretion Rate and Increases Insulin Clearance in Nondiabetic, Insulin-Resistant Individuals. Diabetes
54: 2447-2452
[Abstract][Full Text]
Geluk, C. A., Asselbergs, F. W., Hillege, H. L., Bakker, S. J.L., de Jong, P. E., Zijlstra, F., van Gilst, W. H.
(2005). Impact of statins in microalbuminuric subjects with the metabolic syndrome: a substudy of the PREVEND Intervention Trial. Eur Heart J
26: 1314-1320
[Abstract][Full Text]
Checa, M.A., Requena, A., Salvador, C., Tur, R., Callejo, J., Espinos, J.J., Fabregues, F., Herrero, J., (Reproductive Endocrinology Interest Group of the,
(2005). Insulin-sensitizing agents: use in pregnancy and as therapy in polycystic ovary syndrome. Hum Reprod Update
11: 375-390
[Abstract][Full Text]
Satoh, H, Terada, H, Uehara, A, Katoh, H, Matsunaga, M, Yamazaki, K, Matoh, F, Hayashi, H
(2005). Post-challenge hyperinsulinaemia rather than hyperglycaemia is associated with the severity of coronary artery disease in patients without a previous diagnosis of diabetes mellitus. Heart
91: 731-736
[Abstract][Full Text]
Bunt, J. C., Tataranni, P. A., Salbe, A. D.
(2005). Intrauterine Exposure to Diabetes Is a Determinant of Hemoglobin A1c and Systolic Blood Pressure in Pima Indian Children. J. Clin. Endocrinol. Metab.
90: 3225-3229
[Abstract][Full Text]
St-Pierre, A. C., Cantin, B., Mauriege, P., Bergeron, J., Dagenais, G. R., Despres, J.-P., Lamarche, B.
(2005). Insulin resistance syndrome, body mass index and the risk of ischemic heart disease. CMAJ
172: 1301-1305
[Abstract][Full Text]
Kiortsis, D N, Mavridis, A K, Vasakos, S, Nikas, S N, Drosos, A A
(2005). Effects of infliximab treatment on insulin resistance in patients with rheumatoid arthritis and ankylosing spondylitis. Ann Rheum Dis
64: 765-766
[Abstract][Full Text]
Hu, G., Jousilahti, P., Barengo, N. C., Qiao, Q., Lakka, T. A., Tuomilehto, J.
(2005). Physical Activity, Cardiovascular Risk Factors, and Mortality Among Finnish Adults With Diabetes. Diabetes Care
28: 799-805
[Abstract][Full Text]
Alssema, M., Dekker, J. M., Nijpels, G., Stehouwer, C. D.A., Bouter, L. M., Heine, R. J.
(2005). Proinsulin Concentration Is an Independent Predictor of All-Cause and Cardiovascular Mortality: An 11-year follow-up of the Hoorn Study. Diabetes Care
28: 860-865
[Abstract][Full Text]
St-Pierre, A. C., Cantin, B., Dagenais, G. R., Mauriege, P., Bernard, P.-M., Despres, J.-P., Lamarche, B.
(2005). Low-Density Lipoprotein Subfractions and the Long-Term Risk of Ischemic Heart Disease in Men: 13-Year Follow-Up Data From the Quebec Cardiovascular Study. Arterioscler. Thromb. Vasc. Bio.
25: 553-559
[Abstract][Full Text]
Kawachi, S.-i., Takeda, N., Sasaki, A., Kokubo, Y., Takami, K., Sarui, H., Hayashi, M., Yamakita, N., Yasuda, K.
(2005). Circulating Insulin-Like Growth Factor-1 and Insulin-Like Growth Factor Binding Protein-3 Are Associated With Early Carotid Atherosclerosis. Arterioscler. Thromb. Vasc. Bio.
25: 617-621
[Abstract][Full Text]
Poirier, P., Lemieux, I., Mauriege, P., Dewailly, E., Blanchet, C., Bergeron, J., Despres, J.-P.
(2005). Impact of Waist Circumference on the Relationship Between Blood Pressure and Insulin: The Quebec Health Survey. Hypertension
45: 363-367
[Abstract][Full Text]
Katakam, P. V. G., Tulbert, C. D., Snipes, J. A., Erdos, B., Miller, A. W., Busija, D. W.
(2005). Impaired insulin-induced vasodilation in small coronary arteries of Zucker obese rats is mediated by reactive oxygen species. Am. J. Physiol. Heart Circ. Physiol.
288: H854-H860
[Abstract][Full Text]
Kragelund, C., Snorgaard, O., Kober, L., Bengtsson, B., Ottesen, M., Hojberg, S., Olesen, C., Kjaergaard, J.-J., Carlsen, J., Torp-Petersen, C., on behalf of the TRACE Study Group,
(2004). Hyperinsulinaemia is associated with increased long-term mortality following acute myocardial infarction in non-diabetic patients. Eur Heart J
25: 1891-1897
[Abstract][Full Text]
El-Atat, F. A., Stas, S. N., McFarlane, S. I., Sowers, J. R.
(2004). The Relationship between Hyperinsulinemia, Hypertension and Progressive Renal Disease. J. Am. Soc. Nephrol.
15: 2816-2827
[Abstract][Full Text]
Kornerup, K., Nordestgaard, B. G., Jensen, T. K., Feldt-Rasmussen, B., Eiberg, J. P., Jensen, K. S., Jensen, J. S.
(2004). Transendothelial exchange of low-density lipoprotein is unaffected by the presence of severe atherosclerosis. Cardiovasc Res
64: 337-345
[Abstract][Full Text]
Charbonnel, B., Dormandy, J., Erdmann, E., Massi-Benedetti, M., Skene, A.
(2004). The Prospective Pioglitazone Clinical Trial in Macrovascular Events (PROactive): Can pioglitazone reduce cardiovascular events in diabetes? Study design and baseline characteristics of 5,238 patients. Diabetes Care
27: 1647-1653
[Abstract][Full Text]
Tan, M. H., Johns, D., Glazer, N. B.
(2004). Pioglitazone Reduces Atherogenic Index of Plasma in Patients with Type 2 Diabetes. Clin. Chem.
50: 1184-1188
[Abstract][Full Text]
Miller, A. W., Tulbert, C. D., Busija, D. W.
(2004). Rosuvastatin treatment reverses impaired coronary artery vasodilation in fructose-fed, insulin-resistant rats. Am. J. Physiol. Regul. Integr. Comp. Physiol.
287: R157-R160
[Abstract][Full Text]
Jensen, J. S., Feldt-Rasmussen, B., Jensen, K. S., Clausen, P., Scharling, H., Nordestgaard, B. G.
(2004). Transendothelial lipoprotein exchange and microalbuminuria. Cardiovasc Res
63: 149-154
[Abstract][Full Text]
Ten, S., Maclaren, N.
(2004). Insulin Resistance Syndrome in Children. J. Clin. Endocrinol. Metab.
89: 2526-2539
[Abstract][Full Text]
Abate, N., Chandalia, M., Snell, P. G., Grundy, S. M.
(2004). Adipose Tissue Metabolites and Insulin Resistance in Nondiabetic Asian Indian Men. J. Clin. Endocrinol. Metab.
89: 2750-2755
[Abstract][Full Text]
Lamarche, B., Desroches, S.
(2004). Metabolic syndrome and effects of conjugated linoleic acid in obesity and lipoprotein disorders: the Quebec experience. Am. J. Clin. Nutr.
79: 1149S-1152S
[Abstract][Full Text]
Schillaci, G., Pirro, M., Vaudo, G., Gemelli, F., Marchesi, S., Porcellati, C., Mannarino, E.
(2004). Prognostic value of the metabolic syndrome in essential hypertension. J Am Coll Cardiol
43: 1817-1822
[Abstract][Full Text]
Cheal, K. L., Abbasi, F., Lamendola, C., McLaughlin, T., Reaven, G. M., Ford, E. S.
(2004). Relationship to Insulin Resistance of the Adult Treatment Panel III Diagnostic Criteria for Identification of the Metabolic Syndrome. Diabetes
53: 1195-1200
[Abstract][Full Text]
Erdos, B., Snipes, J. A., Miller, A. W., Busija, D. W.
(2004). Cerebrovascular Dysfunction in Zucker Obese Rats Is Mediated by Oxidative Stress and Protein Kinase C. Diabetes
53: 1352-1359
[Abstract][Full Text]
Winer, N., Sowers, J. R.
(2004). Epidemiology of Diabetes. J Clin Pharmacol
44: 397-405
[Abstract][Full Text]
Yokoyama, H., Emoto, M., Fujiwara, S., Motoyama, K., Morioka, T., Komatsu, M., Tahara, H., Koyama, H., Shoji, T., Inaba, M., Nishizawa, Y.
(2004). Quantitative Insulin Sensitivity Check Index and the Reciprocal Index of Homeostasis Model Assessment Are Useful Indexes of Insulin Resistance in Type 2 Diabetic Patients with Wide Range of Fasting Plasma Glucose. J. Clin. Endocrinol. Metab.
89: 1481-1484
[Abstract][Full Text]
Pfutzner, A., Kunt, T., Hohberg, C., Mondok, A., Pahler, S., Konrad, T., Lubben, G., Forst, T.
(2004). Fasting Intact Proinsulin Is a Highly Specific Predictor of Insulin Resistance in Type 2 Diabetes. Diabetes Care
27: 682-687
[Abstract][Full Text]
Rewers, M., Zaccaro, D., D'Agostino, R., Haffner, S., Saad, M. F., Selby, J. V., Bergman, R., Savage, P.
(2004). Insulin Sensitivity, Insulinemia, and Coronary Artery Disease: The Insulin Resistance Atherosclerosis Study. Diabetes Care
27: 781-787
[Abstract][Full Text]
Fonseca, V., Desouza, C., Asnani, S., Jialal, I.
(2004). Nontraditional Risk Factors for Cardiovascular Disease in Diabetes. Endocr. Rev.
25: 153-175
[Abstract][Full Text]
McGavock, J. M., Mandic, S., Vonder Muhll, I., Lewanczuk, R. Z., Quinney, H. A., Taylor, D. A., Welsh, R. C., Haykowsky, M.
(2004). Low Cardiorespiratory Fitness Is Associated With Elevated C-Reactive Protein Levels in Women With Type 2 Diabetes. Diabetes Care
27: 320-325
[Abstract][Full Text]
Harsch, I. A., Schahin, S. P., Radespiel-Troger, M., Weintz, O., Jahreiss, H., Fuchs, F. S., Wiest, G. H., Hahn, E. G., Lohmann, T., Konturek, P. C., Ficker, J. H.
(2004). Continuous Positive Airway Pressure Treatment Rapidly Improves Insulin Sensitivity in Patients with Obstructive Sleep Apnea Syndrome. Am. J. Respir. Crit. Care Med.
169: 156-162
[Abstract][Full Text]
Herron, K. L., Fernandez, M. L.
(2004). Are the Current Dietary Guidelines Regarding Egg Consumption Appropriate?. J. Nutr.
134: 187-190
[Full Text]
Johansson, B.-L., Sundell, J., Ekberg, K., Jonsson, C., Seppanen, M., Raitakari, O., Luotolahti, M., Nuutila, P., Wahren, J., Knuuti, J.
(2004). C-peptide improves adenosine-induced myocardial vasodilation in type 1 diabetes patients. Am. J. Physiol. Endocrinol. Metab.
286: E14-E19
[Abstract][Full Text]
Campia, U., Sullivan, G., Bryant, M. B., Waclawiw, M. A., Quon, M. J., Panza, J. A.
(2004). Insulin impairs endothelium-dependent vasodilation independent of insulin sensitivity or lipid profile. Am. J. Physiol. Heart Circ. Physiol.
286: H76-H82
[Abstract][Full Text]
Abate, N., Carulli, L., Cabo-Chan, A. Jr., Chandalia, M., Snell, P. G., Grundy, S. M.
(2003). Genetic Polymorphism PC-1 K121Q and Ethnic Susceptibility to Insulin Resistance. J. Clin. Endocrinol. Metab.
88: 5927-5934
[Abstract][Full Text]
Perry, C. G., Spiers, A., Cleland, S. J., Lowe, G. D. O., Petrie, J. R., Connell, J. M. C.
(2003). Glucocorticoids and Insulin Sensitivity: Dissociation of Insulin's Metabolic and Vascular Actions. J. Clin. Endocrinol. Metab.
88: 6008-6014
[Abstract][Full Text]
McLaughlin, T., Abbasi, F., Cheal, K., Chu, J., Lamendola, C., Reaven, G.
(2003). Use of Metabolic Markers To Identify Overweight Individuals Who Are Insulin Resistant. ANN INTERN MED
139: 802-809
[Abstract][Full Text]
Hurst, R. T., Lee, R. W.
(2003). Increased Incidence of Coronary Atherosclerosis in Type 2 Diabetes Mellitus: Mechanisms and Management. ANN INTERN MED
139: 824-834
[Abstract][Full Text]
Previous
