AJH
1992;
5:502-505
Metabolic Cardiovascular Risk Factors and Sodium Sensitivity in Hypertensive Subjects L Lind, H. Lithell, LB. Gustafsson, T. Pollare, and S. Ljunghall
Hypertension has previously been suggested to be a part of a metabolic syndrome also involving hyperlipidemia, hyperinsulinemia, and decreased insulin sensitivity. In the present study, 10 untreated hy pertensive subjects were challenged with a highsalt diet (20 g NaCl) for 1 week after 7 days on a low-salt diet ( < 3 g). The difference in mean blood pressure (MBP) at the end of the high-salt diet ν the low-salt diet was denoted salt sensitivity. We re lated the salt sensitivity to indices of glucose and lipid metabolism and studied the effect of salt dep rivation on these metabolic variables. Salt sensitivity was found to be significantly correlated to HDL cholesterol (r = 0.79, Ρ < .007), insulin sensitivity (M value at the euglycemic clamp, r = 0.68, Ρ < .003), and fasting serum insulin
I
(r = 0.69, Ρ < .04). Salt deprivation induced an in crease in fasting insulin (P < .03), but did not sig nificantly affect any other indices of glucose and lipid metabolism. In conclusion, our study shows that hyperinsu linemia, decreased sensitivity to insulin, and low levels of HDL cholesterol were most commonly seen in hypertensive subjects with a low sodium sensitivity. A putative mechanism might be an in creased activity in pressor systems also affecting glucose and lipid metabolism. Am J Hypertens 1992;5:502-505
KEY WORDS: Insulin, lipids, cholesterol, hyperten sion, salt.
n past years, several authors have suggested that essential hypertension is part of a metabolic syn drome also involving hyperlipidemia with low levels of HDL cholesterol, hyperinsulinemia, de creased insulin sensitivity, and a decreased glucose tolerance. Essential hypertension does not appear to be a homogeneous disorder and different classifications have been proposed, one of which is based on the renin status. According to this classification, the hyperten sive subjects with the highest levels of plasma renin activity (PRA) and aldosterone displayed hyperinsulin emia and decreased levels of HDL cholesterol. Another classification system that has gained interest
in recent years is based upon sodium sensitivity defined as the blood pressure response when the hypertensive subject is challenged with a high-salt diet after a low salt diet for 1 w e e k . As salt-resistant subjects have been found to have the highest PRA and aldosterone levels, one might suspect that these subjects also would show a decreased insulin sensitivity and low levels of HDL cholesterol. The primary aim of our study was to relate sodium sensitivity to metabolic cardiovascular risk factors such as insulin sensitivity and lipid derangements. Because many physicians include salt restriction in the antihy pertensive treatment, the secondary aim of the present study was to examine the effects of an altered salt intake on glucose and lipid metabolism.
Received August 23, 1991. Accepted April 14, 1991. From the Departments of Internal Medicine and Geriatrics, Univer sity Hospital, Uppsala, Sweden. Address correspondence and reprint requests to Professor Sverker Ljunghall, Department of Internal Medicine, University Hospital, S-751 85 Uppsala, Sweden.
MATERIALS AND M E T H O D S
1-5
6
7
© 1992 by the American Journal of Hypertension, Inc.
Downloaded from https://academic.oup.com/ajh/article-abstract/5/8/502/357231 by East Carolina University user on 03 April 2018
8 - 1 0
Eleven subjects with no medication were recruited from a general health screening program in Uppsala, Swe den. They showed a diastolic blood pressure of less than 0895-7061/92/$5.00
AJH-AUGUST
1992-VOL
5, NO. 8
INSULIN, LIPIDS, SALT SENSITIVITY
95 mm Hg at the health screening and at a subsequent visit to the outpatient clinic. The subjects were free of cardiovascular disease, and secondary forms of hyper tension were excluded as far as possible. The mean age of the five men and six women was 67 ± 3.9 years. Each individual was hospitalized at a metabolic ward. The first 2 days were considered a control period in which the subjects were given a Swedish standard diet. Thereafter, the participants were placed on a low-salt diet for 7 days, followed by 1 week of a high-salt diet. The blood pressure was measured four times daily (8 AM, noon, 6 PM, and 10 PM) by a mercury sphygmomanome ter first in the supine position after 15 min rest, and then after 2 min in the standing position. Mean blood pres sure (MBP) was calculated as pulse pressure/3 + diastolic blood pressure. The MBP at the seventh day of each diet period was the mean of the four different recordings during that day. The sodium sensitivity was defined as MBP at the seventh day of the high-salt diet minus MBP at the seventh day at the low salt diet. An intravenous glucose tolerance test (IVGTT) was performed on the sixth day of the different diets while we drew blood samples for determination of lipids and performed a euglycemic clamp test on the seventh day of both the low- and high-salt diets. The diet was planned to be as similar as possible to the patients' ordinary diet except for the salt load. The con tents of protein, fat, and carbohydrates were calculated to be 13, 40, and 49 energy percent (E%), respectively. The content of sodium chloride in the low-salt diet was 2.1 g/8.4 MJ (2000 kcal), and at the most 2.9 g in 11.8 MJ (2800 kcal). The diet was worked out as a 1-week menu. One basic menu with an energy level of 6.7 MJ (1600 kcal) was planned and adjusted for body weight (BW). The patients got 30 to 35 kcal/kg BW of that menu. In that way, the patients' BW remained steady during the dietary periods. We added 17 g of sodium chloride to the low-salt diet to reach the high salt diet. The IVGTT was performed after an overnight fast. We sampled blood for glucose and insulin analyses be fore the glucose injection started. Glucose was given as a 5 0 % glucose solution, 0.5 g glucose/kg BW, for 2 min. The mean of the insulin values after 4 and 6 min was denoted the peak value. The elimination rate (K value) of glucose was calculated according to Ikkos and Luft. The hyperinsulinemic euglycemic clamp technique has been described in detail by deFronzo et a l . A constant rate of semisynthetic regular human insulin (Actrapid Human; Novo, Denmark) was continuously infused in travenously at a rate of 56 mU/m /min in all subjects giving a mean plasma insulin concentration of 92 mU/ L. We measured plasma glucose every 5 min in arterialized venous blood and we adjusted the rate of constant infusion of a 2 0 % glucose solution to keep plasma glu cose at a euglycemic level (5.3 mmol/L). The mean glu 11
12
2
Downloaded from https://academic.oup.com/ajh/article-abstract/5/8/502/357231 by East Carolina University user on 03 April 2018
503
cose (M) uptake was calculated for the last 60 min of the clamp. We analyzed blood glucose with a glucose oxidase method and serum insulin with a commercial kit (Phadebas; Pharmacia, Uppsala, Sweden). After precipita tion of very low and low density lipoproteins by phosphotungstate/MgCl cholesterol and triglyceride concentrations in serum and HDL were analyzed with enzymatic methods (Boehringer Mannheim, Mann heim, Germany) in a centrifugal analyzer. The study was approved by the Ethics Committee of Uppsala University. All participants gave informed consent. One of the subjects (a 64-year-old man) discontinued the study after 3 days of the high-salt diet because of nausea. Two other subjects also complained of nausea from the high salt intake but completed the protocol. The compliance to the diets was good, as measured by urinary collections analyzed for sodium. 2/
Statistics The relationships between sodium sensitiv ity and the metabolic variables were determined using Pearson's correlation coefficient. The differences in metabolic variables between the different diets were evaluated with a Student's paired t test. Two-tailed sig nificance values are given. RESULTS The sodium sensitivity ranged from — 2 mm Hg to + 1 7 mm Hg (Figure 1), and because no clearcut value could separate the subjects into two groups, we treated so dium sensitivity as a continuous variable. After 1 week on the low-salt diet, standing salt sensitivity was signifi cantly correlated to HDL cholesterol (r = 0.79, Ρ < .007) but not to other lipids. Standing sodium sensitivity was also significantly correlated to the Μ value at the clamp (r = 0.68, Ρ < .03), whereas supine sodium sensi tivity was stronger correlated to fasting insulin (r = 0.69, Ρ < .04) than standing sodium sensitivity (r = 0.56, Ρ = .09). During the high-salt diet, standing sodium sensitivity was significantly correlated to HDL cholesterol (r = 0.75, Ρ < .02), although the relations to the Μ value at the clamp and fasting insulin were weaker than on the low-salt diet (r = 0.47, Ρ = .20 and r = —0.50, Ρ = .14, respectively). After 1 week of saltloading following the low-salt diet, fasting insulin was decreased compared with the value obtained during the low-salt diet (Table 1). After correcting for the hemodilution seen during salt-loading (serum albumin de creased by 2 g/L and hemoglobin decreased by 14 g/L) no other metabolic variables changed significantly after salt-loading. DISCUSSION The hypertensive subjects with the lowest sensitivity to salt showed the highest fasting insulin values, the low est insulin sensitivity, and the lowest HDL cholesterol in
504
AJH-AUGUST
LIND E T AL
1992-VOL
5, NO. 8
As the hypertensive subjects with the lowest sensitiv ity to salt have been shown to present with the highest levels of P R A , the present results are in accordance with a recent study in which hypertensive subjects with the highest PRA and aldosterone levels showed hyper insulinemia and decreased HDL cholesterol levels. The importance of these findings has previously been con firmed in a report showing an increased number of car diovascular events in hypertensive subjects with a highrenin profile. Future studies will determine if this is also the case for hypertensives who are salt-resistant. However, the present study is not in agreement with a recent report involving hyperinsulinemia in salt-sensi tive subjects. Although the protocol for the investigaton of salt sensitivity appears similar in both studies, our study involved essential hypertensive patients above middle age whereas the cited study involved young normotensive subjects. The different study samples may therefore explain the different results. In the present study, the relationship between the metabolic risk factors and sodium sensitivity was strong est when we measured sodium sensitivity in the stand ing position and when we measured metabolic risk fac tors during the low-salt diet. Both of these conditions evoke a degree of sympathetic nerve activation that could be a common determination between low-salt sen sitivity and deranged metabolic cardiovascular risk fac tors. Indeed, it has been shown that plasma levels of norepinephrine were higher during a low-salt intake than during salt loading in salt-resistant hypertensive subjects. However, as no measurement of sympathetic 3,5-1 1 • . . • • • · activity was performed in this study, this has yet to be -2 0 2 4 6 8 10 12 14 16 18 studied. SALT SENSITIVITY (mmHg) The only significant change in glucose and lipid me FIGURE 1. Relationship between standing salt sensitivity and tabolism induced by alterations in the salt intake in our insulin sensitivity during euglycemic clamp (M) (top, r = 0.68, study was an increase in fasting insulin during the lowΡ < .03) and HDL-cholesterol (bottom, r = 0.79,P< .007). salt intake compared with the salt-loading period. The reason for this increase in fasting insulin is unclear as our study. Because low levels of both HDL cholesterol both fasting glucose and insulin sensitivity measured and hyperinsulinemia are powerful cardiovascular risk during clamp were unaltered. However, the raised insu factors, it therefore seems likely that hypertensive sub lin level during the low-salt intake is in accordance with jects with low sensitivity to salt are more prone to cardio a previous report of raised levels of this hormone during vascular events (such as myocardial infarction) than are a preoral glucose load while low-salt intake was admin istered to hypertensive subjects. salt-sensitive hypertensives. It has previously been shown that subjects with the The results from these two studies do not support the lowest sensitivity to salt do not retain salt when sub recommendation of a reduction in NaCl intake to im jected to salt loading, compared with hypertensive sub prove glucose tolerance. jects with a high salt sensitivity. Therefore, it has been In conclusion, the present study shows that hyperin postulated that hypertensive subjects with low salt sen sulinemia, decreased sensitivity to insulin, and low sitivity have a raised blood pressure primarily on a va levels of HDL cholesterol were most commonly seen in soconstrictor basis because of a high activity in pressor hyperintensive subjects with a low sodium sensitivity. systems. Thus, the mechanisms involved in the vaso As both hyperinsulinemia and low levels of HDL cho constriction seen in subjects with low sodium sensitivity lesterol are known cardiovascular risk factors, hyper might also be involved in deviations in cardiovascular tensive subjects with a low sensitivity to salt might there risk factors such as hyperinsulinemia, decreased insulin fore be prone to cardiovascular events. A putative sensitivity, and low levels of HDL cholesterol. mechanism linking low salt sensitivity and the aboveMl
H D L - C H O L E S T E R O L (mmol/l) I
8,9
7
13
4
5
6
7
8,9
8
Downloaded from https://academic.oup.com/ajh/article-abstract/5/8/502/357231 by East Carolina University user on 03 April 2018
AJH-AUGUST
1992-VOL
5, NO. 8
INSULIN, LIPIDS, SALT SENSITIVITY
505
TABLE 1. METABOLIC CARDIOVASCULAR RISK FACTORS DURING THE DIFFERENT DIETS Low-Salt Diet Fasting blood glucose (mmol/L) Fasting insulin (mU/L) Insulin peak at IVGTT (mU/L) Μ value during clamp (mg/kg/min) Insulin level during clamp (mU/L) Κ value at IVGTT VLDL triglycerides (mmol/L) LDL cholesterol (mmol/L) HDL cholesterol (mmol/L) Serum triglycerides (mmol/L) Serum cholesterol (mmol/L)
5.0 7.3 53 5.6 119 1.07 1.1 4.5 1.0 1.7 5.9
±0.71 ± 3.4 ±24 ± 1.5 ±32 ±0.27 ±0.64 ±0.41 ±0.29 ±0.75 ±0.51
High-Salt Diet 4.8 4.5 52 5.4 107 0.98 0.90 4.1 0.95 1.5 5.5
±0.56 ± 2.3 ±26 ± 1.4 ±22 ± 0.27 ± 0.27 ±0.46 ± 0.23 ±0.53 ±0.57
Ρ NS
1992;
5:502-505
Metabolic Cardiovascular Risk Factors and Sodium Sensitivity in Hypertensive Subjects L Lind, H. Lithell, LB. Gustafsson, T. Pollare, and S. Ljunghall
Hypertension has previously been suggested to be a part of a metabolic syndrome also involving hyperlipidemia, hyperinsulinemia, and decreased insulin sensitivity. In the present study, 10 untreated hy pertensive subjects were challenged with a highsalt diet (20 g NaCl) for 1 week after 7 days on a low-salt diet ( < 3 g). The difference in mean blood pressure (MBP) at the end of the high-salt diet ν the low-salt diet was denoted salt sensitivity. We re lated the salt sensitivity to indices of glucose and lipid metabolism and studied the effect of salt dep rivation on these metabolic variables. Salt sensitivity was found to be significantly correlated to HDL cholesterol (r = 0.79, Ρ < .007), insulin sensitivity (M value at the euglycemic clamp, r = 0.68, Ρ < .003), and fasting serum insulin
I
(r = 0.69, Ρ < .04). Salt deprivation induced an in crease in fasting insulin (P < .03), but did not sig nificantly affect any other indices of glucose and lipid metabolism. In conclusion, our study shows that hyperinsu linemia, decreased sensitivity to insulin, and low levels of HDL cholesterol were most commonly seen in hypertensive subjects with a low sodium sensitivity. A putative mechanism might be an in creased activity in pressor systems also affecting glucose and lipid metabolism. Am J Hypertens 1992;5:502-505
KEY WORDS: Insulin, lipids, cholesterol, hyperten sion, salt.
n past years, several authors have suggested that essential hypertension is part of a metabolic syn drome also involving hyperlipidemia with low levels of HDL cholesterol, hyperinsulinemia, de creased insulin sensitivity, and a decreased glucose tolerance. Essential hypertension does not appear to be a homogeneous disorder and different classifications have been proposed, one of which is based on the renin status. According to this classification, the hyperten sive subjects with the highest levels of plasma renin activity (PRA) and aldosterone displayed hyperinsulin emia and decreased levels of HDL cholesterol. Another classification system that has gained interest
in recent years is based upon sodium sensitivity defined as the blood pressure response when the hypertensive subject is challenged with a high-salt diet after a low salt diet for 1 w e e k . As salt-resistant subjects have been found to have the highest PRA and aldosterone levels, one might suspect that these subjects also would show a decreased insulin sensitivity and low levels of HDL cholesterol. The primary aim of our study was to relate sodium sensitivity to metabolic cardiovascular risk factors such as insulin sensitivity and lipid derangements. Because many physicians include salt restriction in the antihy pertensive treatment, the secondary aim of the present study was to examine the effects of an altered salt intake on glucose and lipid metabolism.
Received August 23, 1991. Accepted April 14, 1991. From the Departments of Internal Medicine and Geriatrics, Univer sity Hospital, Uppsala, Sweden. Address correspondence and reprint requests to Professor Sverker Ljunghall, Department of Internal Medicine, University Hospital, S-751 85 Uppsala, Sweden.
MATERIALS AND M E T H O D S
1-5
6
7
© 1992 by the American Journal of Hypertension, Inc.
Downloaded from https://academic.oup.com/ajh/article-abstract/5/8/502/357231 by East Carolina University user on 03 April 2018
8 - 1 0
Eleven subjects with no medication were recruited from a general health screening program in Uppsala, Swe den. They showed a diastolic blood pressure of less than 0895-7061/92/$5.00
AJH-AUGUST
1992-VOL
5, NO. 8
INSULIN, LIPIDS, SALT SENSITIVITY
95 mm Hg at the health screening and at a subsequent visit to the outpatient clinic. The subjects were free of cardiovascular disease, and secondary forms of hyper tension were excluded as far as possible. The mean age of the five men and six women was 67 ± 3.9 years. Each individual was hospitalized at a metabolic ward. The first 2 days were considered a control period in which the subjects were given a Swedish standard diet. Thereafter, the participants were placed on a low-salt diet for 7 days, followed by 1 week of a high-salt diet. The blood pressure was measured four times daily (8 AM, noon, 6 PM, and 10 PM) by a mercury sphygmomanome ter first in the supine position after 15 min rest, and then after 2 min in the standing position. Mean blood pres sure (MBP) was calculated as pulse pressure/3 + diastolic blood pressure. The MBP at the seventh day of each diet period was the mean of the four different recordings during that day. The sodium sensitivity was defined as MBP at the seventh day of the high-salt diet minus MBP at the seventh day at the low salt diet. An intravenous glucose tolerance test (IVGTT) was performed on the sixth day of the different diets while we drew blood samples for determination of lipids and performed a euglycemic clamp test on the seventh day of both the low- and high-salt diets. The diet was planned to be as similar as possible to the patients' ordinary diet except for the salt load. The con tents of protein, fat, and carbohydrates were calculated to be 13, 40, and 49 energy percent (E%), respectively. The content of sodium chloride in the low-salt diet was 2.1 g/8.4 MJ (2000 kcal), and at the most 2.9 g in 11.8 MJ (2800 kcal). The diet was worked out as a 1-week menu. One basic menu with an energy level of 6.7 MJ (1600 kcal) was planned and adjusted for body weight (BW). The patients got 30 to 35 kcal/kg BW of that menu. In that way, the patients' BW remained steady during the dietary periods. We added 17 g of sodium chloride to the low-salt diet to reach the high salt diet. The IVGTT was performed after an overnight fast. We sampled blood for glucose and insulin analyses be fore the glucose injection started. Glucose was given as a 5 0 % glucose solution, 0.5 g glucose/kg BW, for 2 min. The mean of the insulin values after 4 and 6 min was denoted the peak value. The elimination rate (K value) of glucose was calculated according to Ikkos and Luft. The hyperinsulinemic euglycemic clamp technique has been described in detail by deFronzo et a l . A constant rate of semisynthetic regular human insulin (Actrapid Human; Novo, Denmark) was continuously infused in travenously at a rate of 56 mU/m /min in all subjects giving a mean plasma insulin concentration of 92 mU/ L. We measured plasma glucose every 5 min in arterialized venous blood and we adjusted the rate of constant infusion of a 2 0 % glucose solution to keep plasma glu cose at a euglycemic level (5.3 mmol/L). The mean glu 11
12
2
Downloaded from https://academic.oup.com/ajh/article-abstract/5/8/502/357231 by East Carolina University user on 03 April 2018
503
cose (M) uptake was calculated for the last 60 min of the clamp. We analyzed blood glucose with a glucose oxidase method and serum insulin with a commercial kit (Phadebas; Pharmacia, Uppsala, Sweden). After precipita tion of very low and low density lipoproteins by phosphotungstate/MgCl cholesterol and triglyceride concentrations in serum and HDL were analyzed with enzymatic methods (Boehringer Mannheim, Mann heim, Germany) in a centrifugal analyzer. The study was approved by the Ethics Committee of Uppsala University. All participants gave informed consent. One of the subjects (a 64-year-old man) discontinued the study after 3 days of the high-salt diet because of nausea. Two other subjects also complained of nausea from the high salt intake but completed the protocol. The compliance to the diets was good, as measured by urinary collections analyzed for sodium. 2/
Statistics The relationships between sodium sensitiv ity and the metabolic variables were determined using Pearson's correlation coefficient. The differences in metabolic variables between the different diets were evaluated with a Student's paired t test. Two-tailed sig nificance values are given. RESULTS The sodium sensitivity ranged from — 2 mm Hg to + 1 7 mm Hg (Figure 1), and because no clearcut value could separate the subjects into two groups, we treated so dium sensitivity as a continuous variable. After 1 week on the low-salt diet, standing salt sensitivity was signifi cantly correlated to HDL cholesterol (r = 0.79, Ρ < .007) but not to other lipids. Standing sodium sensitivity was also significantly correlated to the Μ value at the clamp (r = 0.68, Ρ < .03), whereas supine sodium sensi tivity was stronger correlated to fasting insulin (r = 0.69, Ρ < .04) than standing sodium sensitivity (r = 0.56, Ρ = .09). During the high-salt diet, standing sodium sensitivity was significantly correlated to HDL cholesterol (r = 0.75, Ρ < .02), although the relations to the Μ value at the clamp and fasting insulin were weaker than on the low-salt diet (r = 0.47, Ρ = .20 and r = —0.50, Ρ = .14, respectively). After 1 week of saltloading following the low-salt diet, fasting insulin was decreased compared with the value obtained during the low-salt diet (Table 1). After correcting for the hemodilution seen during salt-loading (serum albumin de creased by 2 g/L and hemoglobin decreased by 14 g/L) no other metabolic variables changed significantly after salt-loading. DISCUSSION The hypertensive subjects with the lowest sensitivity to salt showed the highest fasting insulin values, the low est insulin sensitivity, and the lowest HDL cholesterol in
504
AJH-AUGUST
LIND E T AL
1992-VOL
5, NO. 8
As the hypertensive subjects with the lowest sensitiv ity to salt have been shown to present with the highest levels of P R A , the present results are in accordance with a recent study in which hypertensive subjects with the highest PRA and aldosterone levels showed hyper insulinemia and decreased HDL cholesterol levels. The importance of these findings has previously been con firmed in a report showing an increased number of car diovascular events in hypertensive subjects with a highrenin profile. Future studies will determine if this is also the case for hypertensives who are salt-resistant. However, the present study is not in agreement with a recent report involving hyperinsulinemia in salt-sensi tive subjects. Although the protocol for the investigaton of salt sensitivity appears similar in both studies, our study involved essential hypertensive patients above middle age whereas the cited study involved young normotensive subjects. The different study samples may therefore explain the different results. In the present study, the relationship between the metabolic risk factors and sodium sensitivity was strong est when we measured sodium sensitivity in the stand ing position and when we measured metabolic risk fac tors during the low-salt diet. Both of these conditions evoke a degree of sympathetic nerve activation that could be a common determination between low-salt sen sitivity and deranged metabolic cardiovascular risk fac tors. Indeed, it has been shown that plasma levels of norepinephrine were higher during a low-salt intake than during salt loading in salt-resistant hypertensive subjects. However, as no measurement of sympathetic 3,5-1 1 • . . • • • · activity was performed in this study, this has yet to be -2 0 2 4 6 8 10 12 14 16 18 studied. SALT SENSITIVITY (mmHg) The only significant change in glucose and lipid me FIGURE 1. Relationship between standing salt sensitivity and tabolism induced by alterations in the salt intake in our insulin sensitivity during euglycemic clamp (M) (top, r = 0.68, study was an increase in fasting insulin during the lowΡ < .03) and HDL-cholesterol (bottom, r = 0.79,P< .007). salt intake compared with the salt-loading period. The reason for this increase in fasting insulin is unclear as our study. Because low levels of both HDL cholesterol both fasting glucose and insulin sensitivity measured and hyperinsulinemia are powerful cardiovascular risk during clamp were unaltered. However, the raised insu factors, it therefore seems likely that hypertensive sub lin level during the low-salt intake is in accordance with jects with low sensitivity to salt are more prone to cardio a previous report of raised levels of this hormone during vascular events (such as myocardial infarction) than are a preoral glucose load while low-salt intake was admin istered to hypertensive subjects. salt-sensitive hypertensives. It has previously been shown that subjects with the The results from these two studies do not support the lowest sensitivity to salt do not retain salt when sub recommendation of a reduction in NaCl intake to im jected to salt loading, compared with hypertensive sub prove glucose tolerance. jects with a high salt sensitivity. Therefore, it has been In conclusion, the present study shows that hyperin postulated that hypertensive subjects with low salt sen sulinemia, decreased sensitivity to insulin, and low sitivity have a raised blood pressure primarily on a va levels of HDL cholesterol were most commonly seen in soconstrictor basis because of a high activity in pressor hyperintensive subjects with a low sodium sensitivity. systems. Thus, the mechanisms involved in the vaso As both hyperinsulinemia and low levels of HDL cho constriction seen in subjects with low sodium sensitivity lesterol are known cardiovascular risk factors, hyper might also be involved in deviations in cardiovascular tensive subjects with a low sensitivity to salt might there risk factors such as hyperinsulinemia, decreased insulin fore be prone to cardiovascular events. A putative sensitivity, and low levels of HDL cholesterol. mechanism linking low salt sensitivity and the aboveMl
H D L - C H O L E S T E R O L (mmol/l) I
8,9
7
13
4
5
6
7
8,9
8
Downloaded from https://academic.oup.com/ajh/article-abstract/5/8/502/357231 by East Carolina University user on 03 April 2018
AJH-AUGUST
1992-VOL
5, NO. 8
INSULIN, LIPIDS, SALT SENSITIVITY
505
TABLE 1. METABOLIC CARDIOVASCULAR RISK FACTORS DURING THE DIFFERENT DIETS Low-Salt Diet Fasting blood glucose (mmol/L) Fasting insulin (mU/L) Insulin peak at IVGTT (mU/L) Μ value during clamp (mg/kg/min) Insulin level during clamp (mU/L) Κ value at IVGTT VLDL triglycerides (mmol/L) LDL cholesterol (mmol/L) HDL cholesterol (mmol/L) Serum triglycerides (mmol/L) Serum cholesterol (mmol/L)
5.0 7.3 53 5.6 119 1.07 1.1 4.5 1.0 1.7 5.9
±0.71 ± 3.4 ±24 ± 1.5 ±32 ±0.27 ±0.64 ±0.41 ±0.29 ±0.75 ±0.51
High-Salt Diet 4.8 4.5 52 5.4 107 0.98 0.90 4.1 0.95 1.5 5.5
±0.56 ± 2.3 ±26 ± 1.4 ±22 ± 0.27 ± 0.27 ±0.46 ± 0.23 ±0.53 ±0.57
Ρ NS
