Body Mass, Blood Pressure, Glucose, and Lipids Does Plasma Insulin Explain Their Relationships? Frangois Cambien, Jean-Michel Warnet, Evelyne Eschwege, Alain Jacqueson, Jacques Lucien Richard, and Gabriel Rosselin Downloaded from http://atvb.ahajournals.org/ by guest on June 17, 2017 Obesity, hypertension, a high plasma level of glucose, and some llpid abnormalities (high plasma levels of cholesterol and triglycerides) often occur in the same individuals. Some authors have postulated that the elevated levels of plasma insulin in obese individuals may explain this association. To explore this hypothesis further, the relationships between body mass index, fasting plasma glucose and insulin, blood pressure, serum lipids, and apoproteins were Investigated in a group of 2144 healthy middle-aged men. Analysis of the data show that the associations between body mass index and blood pressure or lipid variables are largely independent of plasma glucose and Insulin. Plasma glucose is strongly related to blood pressure in nonobese subjects. Plasma Insulin is not associated with blood pressure independently of body mass index and plasma glucose; however, the simultaneous elevation of body mass index, plasma glucose, and insulin is strongly associated with blood pressure. The results also confirm that plasma insulin is positively related to triglycerides and negatively related to high density Iipoprotein cholesterol independently of plasma glucose and body mass index. (Arteriosclerosis 7:197-202, March/April 1987) I tein lipase and on VLDL synthesis. These observations are of clinical importance because if insulin is a determinant of either blood pressure or lipoproteins levels, it might at least partly explain the frequent association of obesity, hypertension, elevated plasma glucose, and lipids or Iipoprotein abnormalities in many individuals, particularly those from industrialized countries and would point to insulin's role in the determinism of coronary heart disease and suggest preventive measures. 1011 The purpose of this analysis is to investigate the independent and interactive "effects" of body mass index (BMI), plasma glucose, and insulin on systolic (SBP) and diastolic (DBP) blood pressure and on some lipid parameters, after adjustment for the possibly confounding factors of age, alcohol consumption, and cigarette smoking. The data used were obtained at the initial examination of the Paris Prospective Study II (PPS II). n a previous work using the data of the Paris Prospective Study I (PPS I),1 we studied the relationship between blood pressure, heart rate, and plasma glucose and insulin levels obtained after an oral load of glucose. Analysis of the results demonstrated that in an active population of middle-aged men, glucose level was independently associated with blood pressure, whereas insulin was not. From that analysis, we concluded that insulin is unlikely to affect the blood pressure level. However, the results of recent clinical2'3 and epidemiologic4 studies have emphasized the possible role of insulin as a determinant of blood pressure level and these observations are supported by physiopathological hypotheses stressing the effect of insulin on sodium transports.5 On the other hand, other investigators have demonstrated an independent relationship between plasma insulin and some plasma lipids and lipoproteins6"9 which could be explained by the effect of insulin on lipopro- Methods F. Cambien and J.L. Richard are from Unite d'Epidemiologie Cardio-vasculaire, Institut National de la Sante et de la Recherche Medicale, Unite 258, Paris. J.M. Warnet and A. Jacqueson are from the Laboratoire de Recherche sur les Maladies Cardio-vasculaires de la Direction des Affaires Sanitaires et Sociales de Paris, Paris. E. Eschwege is from Unite de Recherche Statistique, Institut National de la Sante et de la Recherche Medicale, Unite 21, Villejuif. G. Rosselin is from Unite de Diabetologie et Etude Radio-immunologique des Hormones Proteiques, Institut National de la Sante et de la Recherche Medicale, Unite 55, Paris, France. The Paris Prospective Study II is organized by the Groupe d'Etude sur I'Epidemiologie de I'Atherosclerose. We thank the Fondation Francaise de la Nutrition and the Haut Comite d'Etude et d'lnformation sur I'Alcoolisme for their financial support. Address for reprints: Dr. F. Cambien, Unite d'Epidemiologie Cardio-vasculaire, INSERM U 258, Hopital Broussais, 96 rue Didot, 75674 Paris Cedex 14, France. Received July 7,1986; revision accepted November 24,1986. Study Population and Testing The reported results are taken from the cross-sectional data obtained from a subgroup of 2144 healthy middleaged men at entry into the PPS II who agreed to participate in the study. These men were not under treatment for hypertension or diabetes. This investigation on cardiovascular risk factors began in 1982, but follow-up data are not yet available. The study population was the male employees of a large public organization in Paris. Each subject answered a series of questionnaires, including one on smoking habits and one on alcohol consumption.12 A fasting blood sample was drawn and extensive biochemical measurements were performed, including plasma glucose, insulin, cholesterol, triglycerides, high density lipo- 197 198 ARTERIOSCLEROSIS V O L 7, No 2, MARCH/APRIL 1987 protein (HDL) cholesterol, apo A-1, and apo B. Blood pressure was measured with subjects resting in a recumbent position by two different examiners using a mercury sphygmomanometer. The same cuff size (12 cm) was used for every subject. The mean of both measurements is used in this analysis; DBP is phase V of Korotkoff; BMI is weight divided by height squared (kg/m2). A total of 143 subjects who were being treated for either hypertension or diabetes were excluded from the analysis. Biochemical Methods Downloaded from http://atvb.ahajournals.org/ by guest on June 17, 2017 Plasma glucose, plasma triglycerides, total cholesterol, and HDL cholesterol after precipitation of very low density lipoprotein (VLDL) and low density lipoprotein (LDL)13 were determined by an automatic enzymatic procedure (Technicon SMA system). Insulin was measured by the radioimmunologic method with separation on talc.14 The apoproteins A-1 and B were simultaneously assayed by immunoelectrodiffusion.15 Statistical Methods The analysis was divided into two parts. First, the dependent variables (blood pressure and lipid parameters) and the independent variables (BMI, plasma glucose, and insulin) were considered as quantitative variables. Standard methods were used to compute the means, standard deviations, and Pearson correlation coefficients.16 The computer program BMDP 1R16 was used to perform the multiple regression analysis shown in Tables 3 and 4. Second, the independent variables were divided according to their approximate upper deciles. This threshold was chosen a priori to get groups of subjects with elevated levels of these variables. To avoid any biased choice no other grouping was attempted. The generated dummy variables are conventionally called overweight, high plasma glucose, and high plasma insulin. The relationships between high plasma glucose and high plasma insulin on the one hand, and the dependent variables on the other hand in nonoverweight and overweight subjects were tested by a two-way analysis of variance after adjustment on covariates, by use of the BMDP 2V program. In the regression analyses and analyses of variance, plasma triglycerides and Insulin were log-transformed to get more normal distributions. Table 1. Mean Values of Variables In This Analysis Variables Age Alcohol consumption (ml/day) Number of cigarettes (/day) Body mass Index (kg/m2) Plasma glucose (mg/100 ml) Plasma Insulin (^U/ml) Systolic blood pressure (mm Hg) Diastollc blood pressure (mm Hg) Cholesterol (mg/100 ml) HDL cholesterol (mg/100 ml) LDL + VLDL cholesterol (mg/100 ml) Trtglycerldes (mg/100 ml) Apo A-1 (mg/100 ml) Apo B (mg/100 ml) The mean values of the variables obtained in 2144 subjects are shown in Table 1. The correlations between the variables are given in Table 2. BMI was slightly correlated with the confounding factors: positively with age and alcohol consumption and negatively with cigarette consumption. It was correlated with SBP, DBP, and with all lipid variables: positively with total cholesterol, LDL + VLDL cholesterol, triglycerides, and apo B; and negatively with HDL cholesterol and apo A-1. Plasma Insulin was not correlated with the confounding factors, whereas plasma glucose was positively correlated with age and alcohol consumption. SBP and DBP were more strongly correlated with plasma glucose than with plasma insulin. Plasma glu- 43.0 + 4.8 42.0 ±32.0 5.9±9.6 25.3 ±2.9 95.6 ±10.6 8.8 ±8.3 134.2±13.7 83.4 ±9.8 214.3 ±39.8 54.0 ±13.2 160.3±41.2 121.2 ±82.3 155.3 ±22.4 94.9 ±25.2 Data are means ± so; n = 2144 subjects. cose was slightly positively correlated with total cholesterol, VLDL + LDL cholesterol, triglycerides, and apo B, but was not correlated with HDL cholesterol or apo A-1. Plasma insulin was slightly negatively correlated with HDL cholesterol and apo A-1, and positively correlated with triglycerides, but was not correlated with total cholesterol, LDL + VLDL cholesterol, or apo B. Multiple Regression Analysis To look for independent associations, a series of multiple regression analyses were performed with blood pressure or the lipid parameters as dependent variables and BMI, plasma glucose, plasma insulin, and the confounding factors as independent variables. Blood Pressure According to the results of the multiple regression analyses given in Table 3, BMI, plasma glucose, age, and alcohol consumption were independently, positively associated with SBP and DBP, whereas plasma insulin was not. According to the t values, plasma glucose appears more strongly associated with DBP than with SBP. Table 2. Correlations of Body Mass Index, Plasma Glucose, and Insulin with All Other Variables Body mass index Results Mean Values and Correlations Means Body mass index Plasma glucose Plasma insulin Age Alcohol consumption Cigarettes per day Systolic blood pressure Diastollc blood pressure Cholesterol HDL cholesterol LDL + VLDL cholesterol Triglycerides Apo A-1 ApoB — 0.100 0.110 -0.069 0.283 0.312 0.159 -0.238 0.230 0.262 -0.112 0.213 Plasma glucose Plasma insulin 0.239 — 0.267 0.168 — 0.150 0.154 -0.002 0.218 0.267 0.135 -0.011 0.134 0.152 -0.012 0.125 -0.048 0.022 -0.020 0.089 0.089 -0.005 -0.140 0.040 0.145 -0.104 0.004 INSULIN, BLOOD PRESSURE AND LIPIDS and diastolic blood pressure; the significant interaction term for DBP reflects the fact that the relationship between high plasma glucose and diastolic blood pressure was stronger when the plasma insulin level was not elevated (Table 6). In overweight subjects, high plasma glucose and high plasma insulin were positively associated with blood pressure. However, the mean values suggest that blood pressure is elevated when both glucose and Insulin levels are elevated but not when only one is Increased. This is further supported by the significant interaction terms in the analysis of variance. Table 3. Multiple Regression Analysis of Blood Pressure Dependent variable Independent variable Body mass index Plasma glucose Plasma insulin (log) Age Alcohol consumption Cigarette smoking Systolic blood pressure Diastolic blood pressure 0.228 (10.3) 0.132 (6.0) 0.009 (0.4) 0.083 (3.9) 0.116 (5.4) -0.015 (0.7) R 2 = 0.124 0.233 (10.7) 0.177 (8.3) 0.024 (1.1) 0.121 (5.8) 0.085 (4.0) -0.046 (2.2) fl2 = 0 .157 199 Cambien et al. Lipid Variables Values are standardized regression coefficients (f values in parentheses). When r > 1.96, p < 0.05; when t > 3.29, p < 0.001; when f > 4.42, p < 0.00001. flz values are significant at p < 0.00001. In nonoverweight subjects, plasma triglycerides were the only lipid variable that was related to high plasma glucose level (Table 7). On the other hand, high plasma insulin was positively associated with triglycerides and negatively associated with HDL cholesterol and apo A-1. Total cholesterol, LDL + VLDL cholesterol, and apo B were not increased in the presence of a high level of plasma insulin. In overweight subjects, high plasma glucose was not significantly related to the lipid variables, whereas high plasma insulin was significantly associated with all lipid variables except apo A-1. Apparently, total cholesterol and apo B are Increased only when both plasma glucose and insulin are elevated and not when only one of them is increased. This is supported by the significant interaction terms in the analysis of variance. Lipid Variables Downloaded from http://atvb.ahajournals.org/ by guest on June 17, 2017 As shown in Table 4, alcohol consumption was positively associated with all lipid variables. BMI and cigarette consumption were positively associated with triglycerides, LDL + VLDL cholesterol and apo B and were negatively associated with HDL cholesterol and apo A-1. Plasma glucose was positively associated with total cholesterol, VLDL + LDL cholesterol, triglycerides, and apo B but not with HDL cholesterol or apo A-1. On the other hand, plasma insulin was positively associated with triglycerides and negatively associated with total cholesterol, HDL cholesterol, apo A-1, and apo B. Discussion Analysis of Variance BMI, plasma glucose, and plasma insulin were then divided according to their approximate upper deciles to get groups of subjects with elevated levels of these variables; the new dummy variables obtained (overweight, high plasma glucose, and high plasma Insulin) are described in Table 5. The mean levels of blood pressure and the lipid variables in the subgroups of the cross classification of these variables are shown in Tables 6 and 7. The analyses of variance were performed separately for nonoverweight and overweight subjects. In the PPS II examination, the fasting values of plasma glucose and insulin were obtained, whereas in the PPS I examination, the fasting and the 2-hour post-load plasma glucose and insulin values were measured. The previously reported1 results of the PPS I concerned post-load values; however, the results using fasting values were very similar (unpublished results). Furthermore, we consider that fasting values might be more appropriate for the study of the interrelationships of glucose and insulin with coronary risk factors since the predictive values of the latter were established in the fasting state. Blood Pressure Blood Pressure In nonoverweight subjects, high plasma glucose was significantly associated with an increase in both systolic In this study, the blood pressure levels are likely to be slightly overestimated in overweight subjects, since the Table 4. Multiple Regression Analysis of Lipid Variables Dependent variable Independent variable Total cholesterol Triglycerides (log) HDL cholesterol LDL + VLDL cholesterol Apo A-1 ApoB Body mass index Plasma glucose Plasma insulin (log) Age Alcohol consumption Cigarette smoking 0.125 (5.5) 0.074 (3.3) -0.044 (2.0) 0.144 (6.7) 0.124 (5.6) 0.045 (2.0) fl2 = 0.076 0.277 (12.7) 0.081 (3.8) 0.069 (3.3) 0.069 (3.3) 0.061 (2.9) 0.183 (8.7) H 2 = 0.159 -0.278 (12.7) 0.016 (0.7) -0.051 (2.4) 0.160 (7.6) 0.209 (9.8) -0.156 (7.4) O 2 = 0.144 0.210 (9.2) 0.066 (3.0) -0.026 (1.2) 0.088 (4.1) 0.053 (2.4) 0.093 (4.2) R2 = 0.079 -0.120 (5.3) -0.006 (0.3) -0.085 (3.9) -0.010 (0.5) 0.267 (12.1) -0.078 (3.6) fl2 = 0.086 0.211 (9.3) 0.068 (3.1) -0.080 (3.6) 0.039 (1.8) 0.068 (3.1) 0.109 (5.0) fl2 = 0.077 Values are standardized regression coefficients (rvalues in parentheses). See footnote of Table 3 for p values. R2 values are significant at p< 0.00001. 200 ARTERIOSCLEROSIS V O L 7, No 2, MARCH/APRIL 1987 Table 5. Body Mass Index, Plasma Glucose, and Insulin in Subgroups of Cross-Classification of Overweight, High Plasma Glucose, and High Plasma Insulin Nonoverweight Overweight Low glucose Low insulin High insulin Number of subjects 1588 24.4±2.1 Body mass index Plasma glucose 92.9 ±7.4 6.3 ± 3.8 Plasma insulin 143 25.3±2.1 92.7 ±7.8 25.1 ± 10.7 Low glucose High glucose High glucose Low insulin High insulin Low insulin High insulin Low insulin High insulin 155 25.2 ±2.2 114.0±6.1 6.8 ±4.2 30 25.8 ±2.2 119.9±12.7 29.9 ±13.6 50 126 30.6 ±2.0 30.8 ±2.1 95.1 ±7.1 96.7±6.6 8.5 ±4.3 26.2 ±10.8 33 30.2 ±1.7 113.8 ±7.8 8.6 ±5.3 19 32.7 + 3.7 122.3 ±26.2 33.9 ±15.3 Values are means ± SD. Body mass index (BMI), plasma glucose, and insulin are divided according to their upper deciles (the dummy variables generated are called overweight (BMI > 28.7 kg/m2), high plasma glucose (glucose > 108 mg/100 ml), and high plasma insulin (insulin > 17 ^U/ml) in the text and tables. Downloaded from http://atvb.ahajournals.org/ by guest on June 17, 2017 same cuff size was used to measure blood pressure in all subjects despite their weights. However, since the analysis was performed separately in nonoverweight and overweight subjects, the results are unlikely to be affected by this error of measurement. The results corroborate those obtained in the previous analysis.1 Both analyses demonstrate that in the entire population blood pressure is more strongly correlated with plasma glucose than with plasma insulin, and that there is no independent relationship between plasma insulin and blood pressure after adjustment for BMI and plasma glucose. However, this overall linear independence in a general male population, does not exclude the possibility of a specific pattern of relationship at the upper extremes of the distributions of BMI, plasma glucose, or insulin. The analysis shows that in nonoverweight subjects, a high plasma glucose level is associated with a mean increase in SBP and DBP of approximately 9 and 7 mm Hg, respectively, whereas high plasma insulin is not independently associated with blood pressure. In overweight subjects, the simultaneous elevation of plasma glucose and insulin is associated with a mean increase in SBP and DBP of approximately 15 and 7 mm Hg, respectively (see Table 6). The strong relationship between BMI and blood pressure is well known 17 ' 18 and its causal nature is generally acknowledged since many experimental and clinical studies have shown that weight reduction is associated with a mean decrease of blood pressure.19'20 However, although many hypotheses have been proposed, the mechanism of this relationship is not yet understood. One of the most recurrent hypotheses points to the increased mean level of insulin observed in obese subjects as a consequence of insulin resistance. Indeed, an elevation of plasma insulin could affect blood pressure by two mechanisms: 1) by acting on sodium transports, it might induce a positive sodium balance and favor an extravascular shift of fluid and sodium;5 2) by acting on the sympathetic nervous system, it might influence norepinephrine release in the circulation.21 An independent association between plasma insulin and hypertension in nonoverweight subjects has been reported in two studies. Berglund et al.22 found a higher insulin level in a group of lean hypertensives unselected for glucose tolerance, than in a group of normotensives of similar weight. In a subgroup of the study sample of the Israel Study of Glucose Intolerance, Obesity and Hypertension, Modan et al. 4 found a relationship between serum insulin and hypertension independent of glucose intolerance and body mass index. In subjects who are not glucose intolerant the relationship between serum insulin and blood pressure was almost identical whether or not the subjects were obese, whereas in glucose intolerant and diabetic subjects this relationship was less obvious (see Figure 2 in reference 4). On the other hand, Christlieb et al. 3 found no relationship between insulin and hypertension in nonobese glucose intolerant subjects, and in the Paris Prospective Study II, there is no relationship between plasma insulin and blood pressure in nonoverweight subjects whether they have a normal or an elevated plasma glucose level. In overweight subjects, the results also differ among studies. An independent association between insulin and blood pressure was found in the Israel Study,4 in the study of Christlieb et al. 3 and in a group of very obese women studied by Lucas et al.2 No association, however, was Table 6. Analysis of Variance of Blood Pressure according to Levels of Plasma Glucose and Insulin in Nonoverweight and Overweight Subjects Two-way analysis of variance* Blood pressure (mm Hg) Nonoverweight subjects Systolic blood pressure Diastolic blood pressure Overweight subjects Systolic blood pressure Diastolic blood pressure Low glucose Low insulin High insulin High glucose Low insulin High insulin Glucose Insulin Interaction 132.2 ±12.5 81.9 ±9.0 135.2 + 17.3 84.3 ±8.5 141.6±17.3 88.9 + 10.9 142.0 ±16.9 86.1 ±12.1 <0.0001 0.0004 0.24 0.86 0.31 0.007 140.7 ±14.4 88.2 ±10.7 139.2 ±14.8 87.6 ±10.4 139.3 ±13.3 89.8 ±12.0 155.2 ±19.7 96.9±11.7 0.013 0.011 0.001 0.026 0.0007 0.045 Values in the first 4 columns are means ± SD; values in the last 3 columns are probability levels. 'Adjusted on the covariates age, alcohol consumption, and cigarette smoking. INSULIN, BLOOD PRESSURE AND LIPIDS Cambien et al. 201 Table 7. Analysis of Variance of Llpld Variables according to Levels of Plasma Glucose and Insulin In Nonoverwelght and Overweight Subjects Two-way analysis of variance* Variables Downloaded from http://atvb.ahajournals.org/ by guest on June 17, 2017 Nonoverweight subjects Total cholesterol Trtglycerides HDL cholesterol VLDL + LDL cholesterol Apo A-1 ApoB Overweight subjects Total cholesterol Triglycerldes HDL cholesterol VLDL + LDL cholesterol Apo A-1 ApoB Low glucose High Insulin Low Insulin High glucose Low Insulin High Insulin Glucose Insulin Interaction 212.5 ±38.5 111.5±73.9 54.8±13.1 157.8 ±39.9 156.0 ±22.0 93.8 ±24.9 208.9 ±38.8 130.7 ±84.4 50.9±11.5 157.9±41.1 150.1 ±20.9 91.0 ±24.3 222.8±38.8 136.3 ±82.0 57.1 ±15.0 165.7 ±42.3 158.9 ±25.7 98.6 ±26.8 221.2 ±37.3 160.7 ±128.7 53.2 ±14.0 168.0 ±36.9 155.8±22.1 97.8 ±25.3 0.10 0.004t 0.60 0.17 0.33 0.13 0.61 0.004 0.004 0.66 0.025 0.57 0.83 0.83 0.86 0.80 0.77 0.74 220.1 ±42.4 163.2 ±102.6 50.0 ±12.5 170.0 ±42.7 153.8±22.2 102.1 ±26.0 224.6 ±47.1 164.9 ±89.4 47.0 ±10.9 177.5±45.2 147.2 ±20.0 103.1 ±25.4 220.9 ±59.4 151.2 ±99.4 48.8±10.1 172.1 ±55.9 144.6 ±26.0 95.0 ±22.6 246.3 ±42.6 234.0 ±157.2 43.6 ±12.1 202.7 ±45.2 150.2 ±24.7 117.2 ±23.1 0.17 0.11 0.084 0.071 0.36 0.34 0.045 0.009 0.050 0.012 0.58 0.012 0.20 0.036 0.39 0.13 0.15 0.013 Data In the first 4 columns are means ± so; values are mg/100 ml. Data in the last 3 columns are probability levels. 'Adjusted on the covariables age, alcohol consumption, and cigarette smoking. tT analysis of variance was performed on the log of triglycerldes. found In the study of Berglund et al. 22 and In the study of Welnsier et al.23 after adjustment for a different Index of fat distribution. In the Paris Prospective Study II, we note a strong interactive association between plasma glucose and insulin and blood pressure In overweight subjects, suggesting that these subjects are at a high risk of hypertension only when they are insulin-resistant. It is hard to explain these different results; the study groups, however, were very different and factors such as the sex-ratio and the degree of obesity could have accounted for the differences. The strong relationship between plasma glucose and blood pressure independent of insullnemla and BMI observed In the PPS II and in the PPS I could be the consequence either of the direct effect of glucose on blood pressure or of the influence of a third factor affecting both these variables. There is not much experimental evidence for a direct action of glucose on factors affecting blood pressure Independently of plasma insulin level. However, the high vascular reactivity observed in diabetics 24 ' a could exist in nondiabetic subjects who have a mild elevation of plasma glucose. As we discussed in our former paper,1 the activity of the sympathetic nervous system could be the link between blood pressure and plasma glucose, and we hypothesize that the pressor effect of the sympathetic nervous system on blood pressure might increase in hyperglycemic subjects if the passive intracellular diffusion of glucose Increases the responsiveness of the smooth vascular cells. Llpld Variables The results of the regression analyses demonstrate an independent relationship between BMI and all the lipid variables. The association was positive with cholesterol, LDL + VLDL cholesterol, triglycerides, and apo B, and negative with HDL cholesterol and apo A-1. Plasma glucose was significantly related to cholesterol, LDL + VLDL cholesterol, triglycerldes, and apo B, but not to HDL cholesterol and apo A-1. Plasma insulin was associated with all the llpld variables except LDL + VLDL cholesterol. The analyses of variance show that in nonoverwelght subjects, high plasma Insulin was more strongly related to the lipid variables than hyperglycemia; this association was positive with the lipid variables usually linked to the risk of cardiovascular diseases (LDL + VLDL cholesterol, triglycerides, and apo B) and negative with the so-called protective factors (HDL cholesterol and apo A-1). In overweight subjects, the patterns of relationship suggest that the state of insulin resistance that corresponds to a simultaneous elevation of plasma glucose and insulin is associated with elevated levels of triglycerides and apo B. However, the relatively small number of subjects in this particular group must be kept in mind. A positive correlation between insulin level and triglycerides has been reported previously.8'8i 9 Some studies have also shown a negative correlation between insulin level and HDL cholesterol6'8>9 especially HDLj. 7 Experimental data indicate that insulin activates llpoproteln llpase activity which Increases chylomicrons and VLDL catabolism in the circulation;29 furthermore, insulin stimulates VLDL synthesis in the liver.27 These two effects probably play a role in the association observed in clinical and epidemiologic studies between insulin and triglycerides. We are not aware of any direct effect of insulin on the synthesis of apo A-1 (the main protein constituent of HDL cholesterol) in the liver. However, the inverse relationship between triglycerides and HDL cholesterol (r = - 0.403 in this study) is well known and suggests that the effect of insulin on the catabolism of VLDL could partly explain the inverse relationship between insulin and HDL cholesterol. Conclusions The results of this epidemiologic study in nondiabetic, middle-aged men do not confirm the association between 202 A R T E R I O S C L E R O S I S V O L 7, No 2, MARCH/APRIL blood pressure and plasma insulin Independent of obesity and plasma glucose observed in other studies. However, insulin resistance, characterized by high corpulence and high plasma glucose and insulin levels is a strong correlate of blood pressure. On the other hand, these results stress the strong relationship between plasma glucose and blood pressure in nonoverweight subjects. As already shown in other studies, plasma insulin is independently positively associated with triglycerides and negatively associated with HDL cholesterol. References Downloaded from http://atvb.ahajournals.org/ by guest on June 17, 2017 1. Camblen F, Jacqueson A, Richard JL, Rosselin G, Duclmetlere P. Associations between systolic blood pressure, heart rate, and post-load plasma glucose and insulin. In: Eschwege E, ed. Advances in diabetes epidemiology. Amsterdam: Elsevier Biomedical Press. 1982:189-196 2. Lucas CP, Estigarrlbla JA, Darga LL, Reaven GM. Insulin and blood pressure in obesity. Hypertension 1985;7:702-706 3. Chrlstlleb AR, Krolewskl AS, Warram JH, Soeldner JS. Is insulin the link between hypertension and obesity? Hypertension 1985;7(suppl ll):ll-54-ll-57 4. Modan M, Halkln H, Almog S, et al. A link between hypertension obesity and glucose intolerance. J Clin Invest 1985; 75:809-817 5. DeFronzo RA. 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Post-heparin plasma lipoprotein lipase and hepatic lipase in diabetes mellitus. Relationship to plasma triglyceride metabolism. Diabetes 1977; 26:11-21 27. Reaven GM, Greefleld MS. Diabetic hypertriglyceridemia. Evidence for three clinical syndromes. Diabetes 1981;30: 66-75 • body mass index • lipoproteins • apoproteins Downloaded from http://atvb.ahajournals.org/ by guest on June 17, 2017 Body mass, blood pressure, glucose, and lipids. Does plasma insulin explain their relationships? F Cambien, J M Warnet, E Eschwege, A Jacqueson, J L Richard and G Rosselin Arterioscler Thromb Vasc Biol. 1987;7:197-202 doi: 10.1161/01.ATV.7.2.197 Arteriosclerosis, Thrombosis, and Vascular Biology is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231 Copyright © 1987 American Heart Association, Inc. All rights reserved. Print ISSN: 1079-5642. 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