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Hyperinsulinemia in Hypertension
Associations With Race, Abdominal Obesity, and Hyperlipidemia
John G. Spangler, MD, MPH;
Ronny A. Bell, PhD;
John H. Summerson, MS;
Joseph C. Konen, MD, MSPH
Arch Fam Med. 1998;7:53-56.
ABSTRACT
Objective To determine the relative contributions of race, sex, abdominal obesity, and hyperlipidemia to the development of hyperinsulinemia among patients with hypertension.
Design Cross-sectional survey.
Setting A large family practice ambulatory care unit in Winston-Salem, NC.
Patients One hundred and forty adult patients with essential hypertension (systolic blood pressure  160 mm Hg or diastolic blood pressure at or above 90 mm Hg on 2 or more occasions) or who were receiving antihypertensive treatment.
Main Outcome Measures Fasting insulin, lipid, and glucose levels; glycosylated hemoglobin; waist-hip ratio; and resting blood pressure.
Methods Among 4 patient subgroups (hypertension alone; hypertension and abdominal obesity; hypertension and hyperlipidemia; and hypertension, abdominal obesity, and hyperlipidemia) logistic regression analysis was used to determine correlates of elevated fasting insulin levels.
Results Controlling for age and blood pressure, black males had the highest fasting insulin levels (135±70 pmol/L [18.8±9.6 µU/mL] and 265 pmol/L [37.0±0.0 µU/mL] [mean±SD] for obese and nonobese black males, respectively); nonobese white males had the lowest fasting insulin levels (23±22 pmol/L [3.2±3.0 µU/mL]). Multivariate logistic regression indicated that the addition of abdominal obesity or hyperlipidemia to pure hypertension more than doubled the risk of hyperinsulinemia (adjusted odds ratio, 2.69; 95% confidence interval, 1.04-6.89; and adjusted odds ratio, 2.62; 95% confidence interval, 0.37-8.6, respectively). The combination of abdominal obesity and hyperlipidemia exerted additive effects among patients with hypertension for elevated insulin levels (adjusted odds ratio, 5.1; 95% CI, 1.59-16.4).
Conclusions Race, sex, abdominal obesity, and hyperlipidemia interact to produce increases in fasting insulin levels. This knowledge may help physicians prevent sequelae from hyperinsulinemia syndrome among their patients with hypertension.
INTRODUCTION
HYPERINSULINEMIA syndrome describes 4 conditions—insulin resistance, hyperlipidemia, abdominal obesity, and hypertension—that occur more frequently together than chance alone would dictate.1 Secondary effects from hyperinsulinemia may cause blood pressure elevations; in fact, hyperinsulinemia is strongly correlated with the development of essential hypertension.1-7 The blood pressure effects mediated by insulin include increases in intracellular calcium of vascular smooth muscle, enhanced renal sodium retention, and increased sympathetic tone.3 Although it remains controversial whether elevated insulin, per se, causes blood pressure elevations,3, 8 elevated insulin levels clearly are associated with increased risk for atherosclerosis, coronary artery disease,3, 9-13 and renal decline14-19 among patients with hyperinsulinemia syndrome. Improvement of hyperinsulinemia among patients with hypertension by either lifestyle intervention or pharmacologic means seems to be a worthy goal even though studies to date have not documented this benefit.
Little is known regarding factors associated with hyperinsulinemia among patients with essential hypertension. For example, although black persons suffer more severe end-organ damage from hypertension compared with white persons,20-21 there is limited information pertaining to the relationship between race and hyperinsulinemia among patients with essential hypertension. Some populations, such as the Pima Indians and Mexican Americans, have high rates of hyperinsulinemia but low rates of hypertension.22-23 Furthermore, although obesity and hyperlipidemia are associated with hyperinsulinemia,1, 24-26 the relative contribution of each of these factors to the development of elevated insulin levels among patients with hypertension is unknown. We evaluated the predictive value of race, abdominal obesity, and hyperlipidemia for the finding of elevated insulin levels among a population of primary care patients with essential hypertension.
PATIENTS AND METHODS
One hundred and forty patients with essential hypertension and without diabetes mellitus were identified from a computerized database at the Family Practice Center of the Bowman Gray School of Medicine, Winston-Salem, NC. Hypertension was defined as having a systolic blood pressure at or above 160 mm Hg or a diastolic blood pressure at or above 90 mm Hg on 2 or more occasions. Patients were also defined as having hypertension if they were being treated for hypertension detected on at least 2 previous examinations. Screening of patients occurred between January 1, 1989, and June 30, 1991.
Patients underwent a brief but standardized physical examination. Height, weight, body mass index (the weight, in kilograms, divided by the height, in meters, squared), and waist-hip circumferences were obtained for each individual by one trained research assistant (J.H.S.). Blood pressure was measured sitting at rest for 5 minutes using a calibrated mercury sphygmomanometer. Medications, smoking status, age, race, and sex were determined by a questionnaire. Patients then submitted a sample of venous blood after an overnight fast for multichannel chemistry evaluation, fasting glucose, fasting insulin, total cholesterol, high-density lipoprotein cholesterol, triglyceride, and calculated low-density lipoprotein cholesterol levels. Glycosylated hemoglobin was measured by the affinity columns method with normal ranges being from 2.9% to 5.1% for our population. Insulin levels were defined as elevated among women if they exceeded 115 pmol/L (16 µU/mL)27 and among men if they exceeded 90 pmol/L (12.5 µU/mL).28
We defined obesity as present if waist-hip ratios exceeded 0.85. Hyperlipidemia was defined as present if fasting triglyceride levels exceeded 2.26 mmol/L (200 mg/dL) and a calculated low-density lipoprotein cholesterol level exceeded 3.36 mmol/L (130 mg/dL). Based on these definitions, the following 4 subgroups of patients were created: (1) those with hypertension alone (n=38); (2) those with hypertension and obesity (n=69); (3) those with hypertension and hyperlipidemia (n=6); and (4) those with hypertension, obesity, and hyperlipidemia (n=27).
Mean values among subgroups were compared by analysis of variance or if variances were unequal, then by Kruskal-Wallis test. Categorical data were analyzed using the  2 test or stepwise logistic regression. The dependent variable in the logistic regression model was an elevated insulin level as defined previously. Independent predictors—race, mean arterial blood pressure, and fasting glucose and glycosylated hemoglobin levels—were studied for the 4 subgroups of patients (subgroup 1, for those with hypertension alone, served as the referent group). The model simultaneously controlled for age, sex, smoking status, duration of hypertension, and type of blood pressure medication used, if any. All calculations were performed using 2 statistical software programs (EpiInfo Version 5.0, USD Inc, Stone Mountain, Ga, and SPSS-PC Version 2.0, SPSS Inc, Chicago, Ill).
RESULTS
Characteristics of the 140 patients with hypertension included in this analysis are listed in Table 1. Three quarters of the patients were white and just more than half were women. Mean systolic and mean arterial blood pressures were slightly elevated and glycemic values were normal. Mean insulin levels, however, were slightly elevated compared with normative values.27-28 Mean total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol levels were slightly elevated, but triglyceride levels were normal. Additionally, 96 patients (69%) had waist-hip ratios greater than 0.85 and 46 patients (33%) had a body mass index of 30 or greater.
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Table 1. Summary Characteristics of Patients With Hypertension*
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Mean fasting insulin levels by patient category reveal an increasing trend with the addition of risk factors to pure hypertension. These insulin levels are 100±60 pmol/L (13.7±8.6 µU/mL) for patients with hypertension alone; 125±80 pmol/L (17.3±11.2 µU/mL) for patients with hypertension plus obesity; 125±65 pmol/L (17.4±8.9 µU/mL) for patients with hypertension plus hyperlipidemia; and 150±80 pmol/L (20.8±10.9 µU/mL) for patients with all 3 conditions (P=.03, Kruskal-Wallis test). Breaking down insulin levels by race and presence or absence of obesity (Table 2), the single nonobese black man exhibited the highest insulin level (265 pmol/L [37.0±0.0 µU/mL]), followed by obese black men (135±70 pmol/L [18.8±9.6 µU/mL]), while nonobese white men exhibited the lowest levels (23±22 pmol/L [3.2±3.0 µU/mL]; P<.02, Kruskal-Wallis test). Insulin levels did not vary by hypertriglyceride, hypercholesterol, and elevated glycosylated hemoglobin status when evaluated by race and the presence or absence of obesity, as shown in Table 2. Further, the receipt or nonreceipt of blood pressure medication did not influence insulin levels (Table 2), nor did the specific type of blood pressure medication used by the patients (data not shown).
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Table 2. Mean Fasting Insulin Levels by Race and Obesity Status for Selected Categories
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Odds ratios for elevated insulin levels are given in Table 3 and have been adjusted for age, sex, smoking status, duration of hypertension, and type of blood pressure medication used, if any. Race, mean arterial blood pressure, and fasting glucose and glycosylated hemoglobin levels did not correlate with insulin levels and were excluded from the model by backward stepwise regression. Duration of hypertension correlated with elevated insulin levels (adjusted odds ratio [AOR], 1.05; 95% confidence interval [CI], 1.01-1.10). In addition, the 4 patient categories were significantly related to elevated insulin levels. The addition of abdominal obesity to pure hypertension (the referent category) more than doubled the risk for an elevated fasting insulin level (AOR, 2.69; 95% CI, 1.04-6.89). While not statistically significant, the addition of hyperlipidemia to hypertension also more than doubled the risk for an elevated insulin level (AOR, 2.62; 95% CI, 0.37-18.6). In an additive fashion, both factors combined with hypertension increased the risk of an elevated insulin level by 5-fold (AOR, 5.11; 95% CI, 1.59-16.4).
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Table 3. Predictors of Elevated Insulin Levels* Among 140 Patients With Hypertension
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COMMENT
These data indicate that 2 components of hyperinsulinemia syndrome—abdominal obesity and hyperlipidemia—exert additive effects on the development of elevated fasting insulin levels among primary care patients with essential hypertension. While evidence strongly suggests that obesity and hypertension correlate strongly with insulin levels,1, 3-7 these are the first data we are aware of that document quantitatively the relationship among these factors in primary care patients with essential hypertension.
These cross-sectional data indicate correlations and not, strictly speaking, risk. Because the components of hyperinsulinemia syndrome are inextricably linked to insulin resistance, and indirectly to insulin levels, it is unknown which factors preceded the others. It also may be artificial to isolate these factors and add them back to "pure" hypertension, given that all may share the same pathogenesis. Further, our results would have been strengthened by the use of glucose or insulin clamp techniques rather than fasting insulin levels to document insulin resistance. Nevertheless, the strong relationship among fasting insulin levels, hypertension, obesity, and hyperlipidemia in this population of primary care patients with hypertension remains clear.
Mean insulin levels vary significantly in this population when evaluated by race, sex, and obesity status. Unfortunately, with few nonobese black men in our study population, we cannot draw firm conclusions regarding the nature of this relationship.
Patients with hypertension are known to exhibit elevated basal and postprandial insulin levels compared with normotensive controls.5, 7, 29-31 Additionally, patients with hypertension who are obese are known to have higher insulin levels than similarly obese patients without hypertension.8 Methods that improve insulin sensitivity, such as aerobic exercise, low-fat diets, weight reduction, and metformin therapy, also improve blood pressure control among patients with essential hypertension. The converse, however, is not true; lowering blood pressure does not by itself improve insulin resistance. While certain antihypertensive medications improve insulin resistance apart from their blood pressure lowering effect (notably, angiotensin-converting enzyme inhibitors,32-34 doxazosin mesylate,35 and prazosin hydrochloride36),  -blockers and diuretics can actually worsen glucose intolerance.33, 37-39 Even though our sample is not large enough to determine variations in the effects on insulin by individual blood pressure agents, these data corroborate other research showing that blood pressure reduction alone is insufficient to reduce the risk of hyperinsulinemia syndrome developing in patients with hypertension.3, 8 This is especially true for those patients with hypertension who have abdominal obesity and hyperlipidemia.
Our results point out to primary care physicians which patients with hypertension are most at risk of hyperinsulinemia syndrome developing. This subset of patients with hypertension includes those who also possess abdominal obesity, elevations in triglyceride or low-density lipoprotein cholesterol levels, and, possibly, obese black men with hypertension. Because of the dramatic increases in risk for cardiovascular3, 9-13 and renal14-19 disease among patients with hyperinsulinemia syndrome, results from our study argue for multifaceted therapy among these patients with hypertension to improve insulin sensitivity and blood pressure control.
AUTHOR INFORMATION
Accepted for publication October 10, 1996.
This study was supported in part by cooperative grant U32CCU-403318 from the Centers for Disease Control and Prevention, Atlanta, Ga.
Corresponding author: John G. Spangler, MD, MPH, Department of Family and Community Medicine, Bowman Gray School of Medicine, Winston-Salem, NC 27157.
From the Department of Family and Community Medicine (Dr Spangler and Mr Summerson) and the Section on Internal Medicine-Gerontology (Dr Bell), Bowman Gray School of Medicine, Winston-Salem, NC, and the Department of Family Medicine, Carolinas Medical Center (Dr Konen), Charlotte, NC.
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