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(Hypertension. 1997;30:641.)
© 1997 American Heart Association, Inc.
Articles |
Is Insulin or Its Precursor Independently Associated With Hypertension?
An Epidemiological Study in Japanese-Brazilians
From the Department of Preventive Medicine, Federal University of São Paulo, São Paulo, Brazil.
Correspondence to Dr Sandra R.G. Ferreira, Universidade Federal de São Paulo, UNIFESP/EPM, Departamento de Medicina Preventiva, Rua Botucatu 740, CEP 04023-062, São Paulo, SP, Brazil. E-mail ferreira{at}medprev.epm.br
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Abstract |
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Abstract Japanese individuals living outside Japan are more susceptible to chronic diseases included in the insulin resistance syndrome. Hyperinsulinemia and hypertension are associated, but large studies adjusting for confounders are still required. The present evaluated if insulin (I) or proinsulin (PI) was associated with hypertension after adjustment for other risk factors, in first (n=238) and second (n=292) generation Japanese-Brazilians, aged 40 to 79 years, living in a developed city in Brazil. Blood pressure (BP) was measured by random-zero sphygmomanometry. People with mean systolic/diastolic BP >140/90 mm Hg or taking antihypertensive drugs were considered hypertensive. Diagnosis of diabetes was based on results of an oral glucose tolerance test using WHO criteria. I and PI after fasting and 2 hours after glucose load were determined by specific immunofluorimetric assays. The first generation was older than the second (65.6±9.2 versus 53.6±8.4 years, P<.01) and male/female ratios were 1.14 and 0.87, respectively. The age-adjusted prevalence of hypertension was 29.2% with no difference between sexes or generations. Higher body mass index (25.2±4.3 versus 23.8±3.3 kg/m2), waist-to-hip ratio (0.939±0.067 versus 0.919±0.073), plasma glucose (6.3±2.3 versus 5.6±1.8 mmol/L), cholesterol (5.74±1.19 versus 5.48±1.08 mmol/L), and creatinine (74±26 versus 83±36 µmol/L) were found among the hypertensives (P<.05). Univariate analyses showed associations of obesity, diabetes, and dyslipidemia with hypertension. Logistic regression analyses demonstrated that 2-hour I (OR, 1.22; 95% CI, 1.02 to 1.46) and fasting PI (OR, 1.14; 95% CI, 1.00 to 1.31) remained significantly associated with hypertension, after adjustment for age, sex, generation, family history of hypertension, smoking habits, waist-to-hip ratio, serum creatinine, glucose intolerance, and dyslipidemia. Japanese-Brazilians have a higher prevalence of hypertension than the general population in Brazil. High levels of 2-hour I, seen in hypertensives, may be interpreted as independent risk factors for hypertension in this population. Our findings suggest that fasting PI should be useful, in addition to insulin, to assess risk factors for hypertension in epidemiological studies.
Key Words: insulin • proinsulin • risk factors • Japanese migrants
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Introduction |
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Populations of Japanese ancestry living outside Japan become more susceptible to metabolic disturbances that may be consequent to insulin resistance contributing to cardiovascular diseases.1 2 3 The cluster of glucose intolerance, dyslipidemia, and hypertension may occur in response to environmental factors, many of which reflect westernization. The largest population of Japanese descendants lives in Brazil, particularly concentrated in the state of Sao Paulo. The Japanese-Brazilians constitute a socially homogeneous community despite their growing integration in political, economic, and cultural development of the country. We previously reported a increased prevalence of self-reported noninsulin-dependent diabetes mellitus (NIDDM) in first- (Issei) and second-generation (Nisei) Japanese-Brazilians when compared with the population in Japan,4 which is in agreement with data obtained in other migrant Japanese populations.1 5 More recently, an epidemiological study was carried out in a random sample of adult Japanese-Brazilians living in a developed area of the country, where the impact of western environment on the prevalence of diseases included in the insulin-resistance syndrome was investigated.6 Hyperinsulinemia accompanying insulin resistance has been pointed out as the link between hypertension, obesity, and glucose intolerance.7 Considering that the association between hyperinsulinemia and blood pressure could vary by ethnicity,8 in the present study we examined the existence of a link between plasma insulin and proinsulin with hypertension in Japanese migrants, after adjustments for glucose tolerance, abdominal adiposity, dyslipidemia, and other cardiovascular risk factors.
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Methods |
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This cross-sectional study was conducted in a developed city of the state of Sao Paulo named Bauru, surrounding the Tropic of Capricorn. Among 2954 urban Japanese-Brazilians in the age group 40 to 79 years, 339 were Issei (pure Japanese person who migrated from Japan to Brazil) and 805 Nisei (pure Japanese person born in Brazil of at least one Issei parent); third and fourth generations and mestizos completed the population. Percentage of refusal to participate was 12%. The sample studied was composed of 238 Issei and 292 randomly selected Nisei in the age group 40 to 79 years. The entire population of second generation was listed in alphabetical order, and every third subject was selected to compose the Nisei group studied. Male/female ratios for Issei and Nisei were 1.10 and 0.87, respectively. Residents in the households were informed about the survey, and the selected subjects were interviewed a few days later. Eligible subjects were scheduled for clinical and laboratory procedures after an overnight fast. All of them were screened by fasting glycemia, measured by glucose-oxidase strips, read in a reflectance meter (Glucostix/Glucometer system, Miles Laboratories, Inc). At the same time, a blood sample was obtained for glucose, lipids, and creatinine determinations. A 75-g solution of anhydrous glucose was administered to the nondiabetic subjects and to those self-reported diabetics with fasting glycemia <11.1 mmol/L, with the exception of those taking insulin. Two hours later, another blood sample was obtained for glucose tolerance classification purposes, according to WHO recommendations. Meanwhile, a questionnaire was administered, and the subjects underwent clinical examination including weight, height, and waist and hip circumferences. Blood pressure was measured three times, in the sitting position, using random-zero sphygmomanometer. The body mass index (BMI) cutoff for obesity was 25 kg/m2 for both sexes. Subjects were considered hypertensive if the mean values of their systolic and/or diastolic (fifth phase) blood pressures were >140 and 90 mm Hg, respectively,9 or if they were taking antihypertensive agents. The criteria for dyslipidemia was triglyceride >2.39 mmol/L or total cholesterol >5.17 mmol/L or LDL cholesterol >0.36 mmol/L or HDL cholesterol <0.90 mmol/L. Prevalence rates were age-adjusted by the direct method, using the sum of the Issei and Nisei population as the standard.
Glucose, cholesterol, and creatinine were
measured by routine methods; insulin and proinsulin were determined by
a monoclonal antibody-based immunofluorimetric assay.10
Data were expressed as mean±SD, and unpaired Student’s t
test was used to compare generations and groups with and without
hypertension. Insulin and proinsulin concentrations were compared
between normotensive and hypertensive subjects using the Mann-Whitney
test. These variables were considered of primary interest when the
associations with hypertension were analyzed. Correlations
between those hormones and blood pressure values were tested by
Spearman’s correlation coefficient. Frequencies of obesity, diabetes,
and dyslipidemia between generations and sexes were
compared by 
2 test. Unconditional logistic
regression analysis was applied to verify the effects of the
factors of main interest, adjusted for other variables (age, sex,
generation, smoking habits, family history of hypertension, obesity,
waist-to-hip ratio, glucose intolerance, and dyslipidemia)
with potentially confounding effects on the risk of
hypertension.11 Diabetic subjects were excluded in this
analysis due to heterogeneity of beta-cell
function among them. Modeling began with the model including insulin
and proinsulin concentrations and all the variables selected in the
crude analysis, using backward elimination of variables
with a probability value more than .05 in each step; to enter the
initial model the variable had to present a value of
P<.02 in the crude analysis. Multiplicative terms
of interaction were used to assess potential interactions between
variables, which would be kept in the final model if statistically
significant. Point and interval estimates of the odds ratio and the
probability value are presented for the final model. Level of
significance was set at P<.05. Data storage and retrieval
were performed with DBASE III Plus software and data analysis
by Stata 5.0 software.
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Results |
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Niseis were younger (53.6±8.4 versus 65.6±9.2 years, P<.00001) and had higher BMI (24.6±3.6 versus 23.7±3.7 kg/m2, P<.005) than Isseis. Age-adjusted prevalence of hypertension in the overall sample was 29.2% (men, 28.1%; women, 30.4%), and rates did not differ between generations (Issei, 29.2%; Nisei, 33.7%) and sexes (Table 1). The prevalence rates ratios of hypertension according to glucose tolerance status showed that diabetes and impaired glucose tolerance were associated with an increased risk of 1.50- and 1.48-fold, respectively (P<.000005). Considering two groups of subjects, normotensive and hypertensive, smoking habits were not different but the latter had higher frequency of family history of hypertension (60.8% versus 47.0%, P<.005). BMI (25.2±4.3 versus 23.8±3.3 kg/m2, P<.001) and waist/hip ratio (0.939±0.067 versus 0.919±0.073, P<.0005) were greater among hypertensives as compared with normotensives. Also, higher frequencies of obesity, diabetes, and dyslipidemia were observed in the hypertensive group (Table 2), which had higher blood glucose, lipid, and creatinine concentrations (Table 3). After the exclusion of subjects with diabetes, a significant difference in the 2-hour insulin concentration (medians, 138.0 and 211.2 pmol/L; P<.005) and fasting (medians, 2.2 and 3.1 pmol/L; P<.05) and 2-hour proinsulin levels (medians, 13.0 and 16.0 pmol/L; P<.005) between normotensive and hypertensive groups was found, but not in the proinsulin/insulin ratio (Table 3). Blood pressure levels did not correlate with insulin or proinsulin values, excluding or not hypertensive subjects treated with antihypertensive agents. The association of hormonal concentrations and hypertension was also investigated after adjustments for age, sex, generation, smoking habits, family history of hypertension, waist-to-hip ratio, serum creatinine, glucose intolerance, and dyslipidemia, using logistic regression analysis. For this purpose, quintiles of insulin and proinsulin values were obtained. Higher quintiles of 2-hour insulin concentration were associated with a significant increase in risk of hypertension, independently of other variables included in the logistic model. The final models (Table 4) showed that odds ratios (OR) for hypertension in subjects with higher 2-hour insulin (OR with each increase of one quintile in 2-hour insulin, 1.22; 95% confidence interval [CI], 1.02 to 1.46) and fasting proinsulin (OR with each increase of one quintile in fasting proinsulin, 1.14; 95% CI, 1.00 to 1.31) were essentially unchanged when terms of interaction and covariables used in the adjustments were excluded. Age, sex, family history of hypertension, waist-to-hip ratio, impaired glucose tolerance, and serum creatinine were also independently associated with increased risk of hypertension in both final models.
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Discussion |
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The influence of environmental factors on the development of noncommunicable chronic diseases has been the target of migrants studies,3 12 13 14 and also our group had focused particularly on NIDDM in Japanese-Brazilians.4 5 Prevalence studies on hypertension in Japanese populations living in Japan are not common, and they generally include several cardiovascular events.15 16 A large variability in prevalence rates of hypertension has been observed, which was associated to different levels of salt intake and alcohol consumption and seasonal variation.15 16 17 Although a gradient in incidence and mortality rates due to cardiovascular diseases in Japanese descendants moving to the United States was known since 1957, the comparison of prevalence data on hypertension is limited by methodological reasons. An overall rate of 14% was verified in Japanese-Americans older than 18 years living in California.18 Our study, focusing on an older age group (40 to 79 years), found a prevalence of hypertension higher than double that of those previously reported. Our findings are in agreement with Fujimoto et al,19 who conducted a survey among second- and third-generation Japanese-Americans in the same age group living in Seattle. On the other hand, these findings are lower than those more recently found in Los Angeles (37%) and Hawaii (43%) and similar to those from Hiroshima, Japan.20 Despite different rates from one study to another, all the results have been compatible with an unfavorable role of the western environment to the development of hypertension and NIDDM. Several evidences have pointed to an association of insulin resistance and hyperinsulinemia with increased risk of both diseases.7 21 22 23 We have the opportunity to examine the association of hypertension with disturbed insulin metabolism in a high-risk population, after adjustment for many potential confounding factors. Previous investigations have found that high plasma insulin concentration in fasting subjects was associated to increased risk of hypertension,7 23 24 25 26 and methodological differences have contributed to discordant results, such as lack of specificity of insulin and proinsulin assays.27 Mechanisms responsible for this association, however, remain speculative, since large prospective studies are still not available. We used a specific assay to measure plasma insulin that did not cross-react with proinsulin, able to assess their possible individual contribution to the risk of hypertension, independently of other known risk factors. Our findings support the notion that glucose-induced hyperinsulinemia and fasting proinsulinemia may increase the risk of hypertension through alterations in metabolic processes other than impaired glucose tolerance or dyslipidemia. This association remained unchanged by adjustments for age, sex, family history of hypertension, waist-to-hip ratio, and dyslipidemia. Among the cluster of metabolic abnormalities seen in a proportion of hypertensive subjects, obesity is also present, particularly of abdominal distribution, characterized by the fat accumulation in visceral tissues. Despite the low frequency of obesity in Japanese descendants, as is the case for our population sample, we demonstrated a higher waist-to-hip ratio in the hypertensive group, a crude anthropometric estimate of visceral adiposity. In fact, this covariable was shown to be significantly associated with the risk of hypertension in the multivariate analyses. The Paris Prospective Study cohort suggested that upper-body fat distribution was an independent predictor of mortality due to cardiovascular disease, after controlling for hyperinsulinemia.28 Regarding increased risk for hypertension, Boyko et al26 examined the association among intra-abdominal fat, fasting plasma insulin and blood pressure in second- and third generation Japanese-Americans. Visceral adiposity measured by computed tomography was shown to be correlated with blood pressure levels, independent of insulin concentration in the second generation. Although we have detected the association of hypertension only with 2-hour insulin, their data could be seen as in agreement with ours, since their multiple linear regression analyses revealed association of insulin and blood pressure, independent of adiposity. Also, our findings are somewhat concordant with the results obtained in two groups of Japanese, with or without hyperinsulinemia, showing higher blood pressure levels among the former.25 Other investigators focused on post–glucose-load insulin levels, obtaining similar results only in lean subjects.29 On the other hand, Baba et al30 were unable to demonstrate this relationship in a small sample of nonobese, nondiabetic, middle-aged Japanese subjects, which may have resulted in inadequate power to disclose this association. In addition, the lack of elevated plasma insulin may not be sufficient to exclude insulin resistance of peripheral tissues. In fact, a study using insulin sensitivity test found no hypertensive effect and suggested that insulin resistance rather than hyperinsulinemia could be more closely associated with nonobese nondiabetic hypertension.31 Besides plasma insulin, our observations suggest that proinsulin concentrations should be measured in epidemiological studies. Despite the low concentration found in the present study, these values were also associated with increased risk of hypertension. Other investigators have already called attention to the usefulness of both insulin and proinsulin, to assess risk factors for cardiovascular diseases.27
The underlying mechanisms involved in the association of insulin levels and high blood pressure are still a matter of speculation. Effects of acute insulin administration, such as sodium retention and adrenergic stimulation,32 33 could corroborate this hypothesis but not in all experiments.34 Although our data suggested that proinsulin and 2-hour insulin concentrations in nonobese nondiabetic Japanese-Brazilians are independent factors associated with hypertension, the cross-sectional nature of the study does not allow the exploration of a cause-effect relationship between these variables. Considering the Japanese migrants at high risk for hypertension and the existence of the association with insulin metabolism disturbance, as demonstrated by our data, we call attention to the potential of long-term prospective studies in this community to clarify this issue.
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Footnotes |
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JBDSG, Japanese-Brazilian Diabetes Study Group
Received March 15, 1997; first decision April 17, 1997; accepted April 17, 1997.
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References |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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1. Taylor R, Zimmett P. Migrant studies in diabetes epidemiology. In: Mann JI, Pyorala K, Teuscher A. eds. Diabetes in Epidemiology Perspective. Edinburg: Churchill Livingstone; 1983:58-77.
2. Hara H, Nagasaki K, Ono S. A comparative study on risk factors of atherosclerosis in Japanese-Americans and Japanese in Hiroshima. JACD. 1985;20:131-143.
3. Fujimoto WY. The growing prevalence of non-insulin-dependent diabetes in migrant populations and its implications for Asia. Diab Res Clin Pract. 1992;15:167-184.[Medline] [Order article via Infotrieve]
4. Iunes M, Franco M, Wakisaka K, Iochida LC, Osiro K, Hirai AT, Matsumura L, Kikuchi M, Ferreira SRG, Miyasaki N. Self-reported prevalence of diabetes mellitus in the 1st (Issei) and 2nd (Nisei) generation of Japanese-Brazilians over 40 years of age. Diab Res Clin Pract. 1994;24(suppl):S53-S57.
5. Fujimoto WY, Leonetti DL, Kinyoun JL, Newell-Morris L, Shuman WP, Storov WC, Walh PW. Prevalence of diabetes mellitus and impaired glucose tolerance among second generation Japanese American men. Diabetes. 1987;36:721-729.[Abstract]
6. Ferreira SRG, Iunes M, Franco LJ, Iochida LC, Hirai A, Vivolo MA. Disturbances of glucose and lipid metabolism in first and second generation Japanese-Brazilians. Diab Res Clin Pract. 1996;34(suppl):S59-S63.
7. Modan M, Halkin H, Almog S, Lusky A, Eshkol A, Shefi M, Shitrit A, Fuchs Z. Hyperinsulinemia: a link between hypertension, obesity and glucose intolerance. J Clin Invest. 1985;75:809-817.[Medline] [Order article via Infotrieve]
8. Saad MF, Lillioja S, Nyomba BL, Castilho C, Ferraro R, De Gregorio M, Ravussin E, Knowler WC, Bennett PH, Howard BV, Bogardus C. Racial differences and the relation between blood pressure and insulin resistance. N Engl J Med. 1991;324:733-739.[Abstract]
9. Joint National Committee on Detection, Evaluation, and
Treatment of High Blood Pressure: 1993 Report. Arch Intern
Med. 1993;153:154-183.
10. Vieira JGH, Nishida SK, Lombardi MT, Tachibana TT, Obara LH, Dalbosco IS, Russo EMK. Comparison of the determination of insulin by a monoclonal antibody-based immunofluorimetric assay and by radioimmunoassay. Braz J Med Biol Res. 1995;28:537-543.[Medline] [Order article via Infotrieve]
11. Hosmer JR, Lemeshow S. Applied Logistic Regression. New York, NY: John Wiley & Sons; 1989.
12. Kagan A, Harris BR, Winkelstein WJ, Johnson KG, Kato H, Syme SL, Rhoads GG, Gay ML, Nichaman MZ, Hamilton HB, Tilloston JL. Epidemiologic studies of coronary heart disease and stroke in Japanese men living in Japan, Hawaii and California: demographic, physical, dietary and biochemical characteristics. J Chronic Dis. 1974;27:345-364.[Medline] [Order article via Infotrieve]
13. Kawate R, Yamakido M, Nishimoto Y, Bennet PH, Hamman RF, Knowler WC. Diabetes mellitus and its vascular complications in Japanese migrants on the island of Hawaii. Diabetes Care. 1979;2:161-170.[Abstract]
14. Angel A, Armstrong MA, Klatsky AL. Blood pressure among Asian-Americans living in Northern California. Am J Cardiol. 1989;15:237-240.
15. Kimura T, Ota M. Epidemiologic study of hypertensive surveys in two areas in Northern Japan. Am J Clin Nutrition. 1965;17:381-390.[Abstract]
16. Tanaka S, Hayase A, Hashimoto A, Takagi Y, Kondo S, Hayashi K, Yamamoto M, Iimura O. Hypertension and cardiovascular diseases in an epidemiological study in Hokkaido, Japan. J Cardiovasc Pharmacol. 1990;16(suppl 7):S83-S86.
17. Ueshima H, Ozawa H, Baba S, Nakamoto Y, Omae T, Shimamoto T, Komachi Y. Alcohol drinking and high blood pressure: data from a 1980 national cardiovascular survey of Japan. J Clin Epidemiol. 1992;45:667-673.[Medline] [Order article via Infotrieve]
18. Stavig GR, Igra A, Leonard AR. Hypertension and related health issues among Asians and Pacific Islanders in California. Public Health Reports. 1988;103:28-37.[Medline] [Order article via Infotrieve]
19. Fujimoto W, Boyko E, Leonetti D, Bergstrom R, Newell-Morris L, Wahl P. Hypertension in Japanese-Americans: the Seattle Japanese-American Community Diabetes Study. Public Health Reports. 1996;111(suppl 2):56-58.
20. Imazu M, Sumida K, Yamabe T, Yamamoto H, Ueda H, Hattori Y, Miyaauchi, Hara H, Yamakido M. A comparison of the prevalence and risk factors of high blood pressure among Japanese living in Japan, Hawaii, and Los Angeles. Public Health Reports. 1996;111(suppl 2):59-61.
21. Warram JH, Martin BC, Krolewski AS, Soeldner JS, Kahn
CR. Slow glucose removal rate and
hyperinsulinemia precede the development of type II
diabetes in the offspring of diabetic parents. Ann Intern
Med. 1990;113:909-915.
22. Lillioja S, Mott DM, Spraul M, Ferraro R, Foley JE, Ravussin E, Knowler WC, Bennett PH, Bogardus C. Insulin resistance and insulin secretory dysfunction as precursors of non-insulin-dependent diabetes mellitus: prospective studies in Pima Indians. N Engl J Med. 1993;1988;329-1992.
23. Pollare T, Lithell H, Berne C. Insulin resistance is a characteristic of primary hypertension independent of obesity. Metab Clin Exp. 1990;39:167-174.[Medline] [Order article via Infotrieve]
24. Haffner SM, Fong D, Hazuda HP, Pugh JA, Patterson JK. Hyperinsulinemia, upper body adiposity, and cardiovascular risk factors in non-diabetics. Metab Clin Exp. 1988;37:338-345.[Medline] [Order article via Infotrieve]
25. Yamada N, Yoshinaga H, Sakurai N, Shimano H, Gotoda T, Ohashi Y, Yazaki Y, Kosaka K. Increased risk factors for coronary artery disease in Japanese subjects with hyperinsulinemia or glucose intolerance. Diabetes Care. 1994;17:107-114.[Abstract]
26. Boyko EJ, Leonetti DL, Bergstrom RW, Newell-Morris L, Fujimoto WY. Visceral adiposity, fasting plasma insulin, and blood pressure in Japanese-Americans. Diabetes Care. 1995;18:174-181.[Abstract]
27. Haffner SM, Mykkanen L, Stern MP, Valdez RA, Heisserman JA, Bowsher RR. Relationship of proinsulin and insulin to cardiovascular risk factors in non-diabetic subjects. Diabetes. 1993;42:1297-1302.[Abstract]
28. Casassus P, Fontbonne A, Thibult N, Ducimetière
P, Richard JL, Claude JR, Warnet JM, Eschwège E.
Upper-body fat distribution: a
hyperinsulinemia-independent predictor of
coronary heart disease mortality: the Paris Prospective
Study. Arterioscler Thromb. 1992;12:1387-1392.
29. Haffner SM, Valdez RA, Hazuda HP, Mitchell BD, Morales PA, Stern MP. Prospective analysis of insulin-resistance syndrome (syndrome X). Diabetes. 1992;41:715-722.[Abstract]
30. Baba T, Kodama T, Tomiyama T, Sohn DR, Ishiaki T. Serum insulin level versus blood pressure: a cross-sectional, case-controlled study in non-obese, middle-aged Japanese subjects with normal glucose tolerance. Diabetic Med. 1994;11:42-49.[Medline] [Order article via Infotrieve]
31. Yokota C, Ikebuchi M, Suzuki M, Norioka M, Ikeda K, Shinozaki K, Harano Y. Insulin resistance rather than hyperinsulinemia more closely associated with essential hypertension. Clin Exp Hypertens. 1995;17:523-536.[Medline] [Order article via Infotrieve]
32. DeFronzo RA, Cooke CR, Andres R, Faloona GR, Davis PJ. The effect of insulin on renal handling of sodium, potassium, calcium, and phosphate in man. J Clin Invest. 1975;55:845-855.[Medline] [Order article via Infotrieve]
33. Rowe JW, Young JB, Minaker KL, Stevens AL, Pallotta J, Landsberg L. Effect of insulin and glucose infusions on sympathetic nervous system activity in normal man. Diabetes. 1981;30:219-225.[Medline] [Order article via Infotrieve]
34. Anderson EA, Balon TW, Hoffmann RP, Sinkey CA, Mark
AL. Insulin increases sympathetic activity but not blood
pressure in borderline hypertensive humans.
Hypertension. 1992;19:621-627.
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