Hostility, Race, and Glucose Metabolism in Nondiabetic Individuals
- Richard S. Surwit, PHD12,
- Redford B. Williams, MD12,
- Ilene C. Siegler, PHD1,
- James D. Lane, PHD1,
- Michael Helms, PHD1,
- Katherine L. Applegate, PHD1,
- Nancy Zucker, PHD1,
- Mark N. Feinglos, MD12,
- Cynthia M. McCaskill, MSN1 and
- John C. Barefoot, PHD1
- 1Department of Psychiatry and Behavioral Sciences; Duke University School of Medicine, Durham, North Carolina and the
- 2Department of Medicine, Duke University School of Medicine, Durham, North Carolina
OBJECTIVE—The present study was designed to determine whether hostility is differentially related to measures of glucose metabolism in African-Americans and Caucasians.
RESEARCH DESIGN AND METHODS—The relationship of hostility, as measured by a subset of the Cook-Medley hostility scale (CMHOST) inventory items, to various parameters of glucose metabolism were examined in a young, healthy sample of male and female African-American and Caucasian volunteers. Fasting blood samples were collected during an inpatient admission, at which time the CMHOST was also administered.
RESULTS—In the entire sample, the CMHOST was found to be significantly correlated with fasting glucose and insulin sensitivity, as measured by the homeostatic model assessment (HOMA). However, the relationship of hostility to these parameters of glucose metabolism was different in African-American and Caucasian subjects. Hostility was significantly related to fasting glucose in African-Americans and to insulin sensitivity and fasting insulin in Caucasian subjects. The relationship of hostility to insulin sensitivity and fasting insulin was partially dependent on BMI in Caucasians, but the relationship of hostility to fasting glucose was unrelated to BMI in African-Americans.
CONCLUSIONS—Our data suggest that the relationship of hostility to measures of glucose metabolism is mediated differently in these two ethnic groups. Therefore, hostility seems to be part of a constellation of risk-related behaviors related to BMI in Caucasians but independently related to fasting glucose in African-Americans.
Hostility is a personality construct (1–4) that has been shown to be a risk factor for coronary artery disease (CAD). A number of studies provide support for hostility as a predictor of coronary events (5–8) and premature mortality from all causes (5). Hostility also has been found to be a correlate of subclinical atherosclerosis (9–11), coronary risk profiles (12), and harmful health behaviors (13). The importance of hostility for health now has been generally confirmed in the literature (14).
Although the mechanism by which hostility may increase risk of CAD is not known, it is generally believed that hostility may increase cardiovascular risk either through risk-related behaviors or neuroendocrine risk factors. These two alternatives have been conceptualized in terms of a health behavior model, a constitutional vulnerability model, and stress moderation models (15). The health behavior model suggests that hostility is associated with high-risk behaviors such as cigarette smoking, high caloric intake, and exercise habits. In contrast, the constitutional vulnerability model implies fundamental physiological differences for hostile individuals, perhaps at the genetic level, that place them at increased risk for disease. Stress moderation models suggest that hostile individuals may be constitutionally more reactive to stress, with their exaggerated stress response leading to an increased risk of disease. Furthermore, hostile individuals may have more stressful social environments because of the nature of their social interactions.
There is some evidence that hostility may also be related to variations in glucose metabolism. Hostility, as measured by the Cook-Medley hostility scale (CMHOST) (2), has been positively correlated with an increase in visceral adiposity and fasting insulin in a sample of American postmenopausal women (16,17), whereas hostility, as measured by the Profile of Mood States (18), was significantly related to average blood glucose, as measured by HbA1c in a sample of Japanese adult men (19). Most recently, small but statistically significant correlations were found between the Hostile Attribution and Aggressive Responding subscales of the CMHOST and fasting plasma insulin in a sample of 1,081 older white men (mean age 63 years) (20). Pathologic analysis suggested that these relationships could be accounted for by the relationship of hostility to BMI. This explanation was consistent with the known relationship of hostility to caloric intake and waist-to-hip ratio.
If hostility is related to abnormal glucose metabolism, this relationship may help explain why hostility is a risk factor for CAD. Higher levels of fasting glucose and insulin and decreased insulin sensitivity themselves are significant risk factors for cardiovascular disease in both diabetic and nondiabetic populations (21–33). Elevated levels of HbA1c in nondiabetic individuals have been shown to be an independent risk factor for increased mortality after myocardial infarction (32), and HbA1c was shown to be a continuously related factor for death from cardiovascular disease as well as all other causes in a population of ∼5,000 men from the European Prospective Investigation into Cancer and Nutrition (33).
Hostility is related to both gender and race; higher values are found in men and African-Americans (34–36). In addition, African-Americans are at increased risk for type 2 diabetes; the prevalence rate is almost twice that in the Caucasian population at most ages (37). However, none of the studies reviewed examined the relationship of hostility to metabolic parameters in African-Americans or compared these relationships among ethnic groups. Three of the studies reviewed above were limited to Caucasians (16,17,20), whereas the fourth studied Japanese men exclusively (19). The present study was designed to determine whether hostility might be a factor in the racial disparity in diabetes prevalence by determining whether higher levels of hostility are differentially associated with higher fasting glucose and insulin levels in an African-American and Caucasian population.
RESEARCH DESIGN AND METHODS
A total of 98 men and women aged 18–48 years were recruited through advertisements in the local media, flyers distributed in supermarkets and other public locations, and outreach screening at civic organizations meetings and other public events. The subjects comprised 35 black women, 21 white women, 28 black men, and 14 white men; mean age was 33.2 years (SD 8.9). Subjects included in this study were part of a larger study (38). Ethnicity was self-reported; therefore, a social definition of ethnicity was used. Recent immigrants and non-English speakers were excluded, independent of ethnic status. All data were collected between 6 October 1999 and 14 September 2001.
After informed consent was obtained, subjects were screened by a psychiatrist to exclude those with medical and/or psychiatric disorders (Diagnostic and Statistical Manual of Mental Disorders, 4th edition criteria) or current chronic use of medication (psychotropic drugs, aspirin, nonsteroidal anti-inflammatory drugs, etc.). To study the relationship of hostility to glucose metabolism in a healthy population, subjects with a history of AIDS, diabetes, heart disease, cancer, epilepsy, kidney disease, or psychiatric disorder and those who were pregnant or hypertensive were not eligible. These criteria were also part of those from the larger study for which subjects were initially recruited (38). Subjects reported to the General Clinical Research Center during the afternoon of the day before blood sampling. They underwent lumbar puncture for collection of cerebral spinal fluid samples for another study (38) and completed the 27-item version of the CMHOST (1,2). Subjects remained in the hospital overnight. They were given a snack at bedtime and fasted for 8 h. Blood samples were drawn by venipuncture the following morning for assessment of glucose and insulin. Plasma glucose was measured by the Beckman Glucose Analyzer (Beckman Instruments, Chicago, IL) and plasma insulin by the Linco immunoassay kit (Linco Labs, St. Louis, MO).
Homeostatic model assessment.
The homeostatic model assessment (HOMA) was used to estimate insulin sensitivity (39). This model uses fasting glucose and insulin values to calculate a derived estimate of insulin resistance by the formula RHOMA = glucose (mg/dl) × insulin (μU)/22.5 and produces a reasonable estimate of insulin sensitivity as derived from clamp techniques (40). The higher the HOMA score, the lower the insulin sensitivity. HOMA values were logarithmically transformed for the analyses.
The most widely used hostility scale in health research is the CMHOST (2) from the Minnesota Multiphasic Personality Inventory (MMPI). It has excellent stability with test-retest correlations of 0.84 across a 4-year period (6) and 0.74 across a 10-year interval (7). The original scale contains 50 items, but a rational analysis of item content revealed that some are not good reflections of hostility (2). In the present study, we administered an abbreviated version of the scale using the 27 items identified in that analysis as indicators of cynicism, hostile affect, and aggressiveness. This briefer scale (CMHOST), which yields a single summary score, has been found to be a better predictor of health outcomes than the full CMHOST scale (2,41).
The relationships between the measures of hostility and the measures of glucose metabolism were tested by simple correlation and by partial correlation including statistical controls for variations in BMI. Statistical analysis was performed using SAS version 8.0 (SAS Institute, Cary, NC). Statistical significance was declared for P values ≤0.05.
The descriptive statistics for the variables in the study are shown in Table 1. There were few differences across gender and ethnic groups. Women reported lower hostility (P < 0.01) and tended to have lower glucose levels (P = 0.05). There was also a trend for African-Americans to have lower glucose levels (P = 0.08), but none of the other tests of main effects or interactions were close to significance.
Table 2 shows the associations between CMHOST and the various measures of glucose metabolism in the complete sample. There were significant correlations between CMHOST and all three measures. None of them were substantially altered by adjustments for BMI. Nonparametric correlations were also computed to evaluate the possibility that the statistics reported in Table 2 were unduly affected by outliers, particularly one African-American woman with an extreme insulin value. The nonparametric correlations did not differ substantially from the Pearson correlations.
The potential moderating influences of gender and ethnicity were also explored. Table 3 shows the correlations when the sample was stratified by gender or ethnicity and the tests for gender or ethnic differences between those correlations. The relationships of CMHOST to insulin were significantly stronger in women than in men in the simple correlations, but adjustment for BMI weakened this difference. The gender differences in the associations of CMHOST with Ln HOMA were also significant in both the simple and adjusted correlations. There was one indication of moderation of the effects by ethnicity. The association of CMHOST with glucose was strong in African-Americans, but it was absent in Caucasians. The difference between the magnitudes of the associations was not significant for the simple correlations, but the comparison were significant after adjustment for BMI.
Further analyses explored the possibility that there were more complicated effects due to the interaction of ethnicity and gender. None of these tests were statistically significant.
Hostility has long been known to be a risk factor for CAD, although the mechanism by which hostility increases this risk is unknown. Recent studies have reported small but significant correlations between various measures of hostility and indexes of glucose metabolism, but most of these studies were not adequately designed to assess such relationships. In the present study, the relationships of hostility, as measured by the CMHOST (40) to various parameters of glucose metabolism, were examined in young, healthy, multiracial subjects. The CMHOST was found to be significantly correlated with fasting glucose and insulin sensitivity, as measured by HOMA (39). These relationships were independent of BMI, which has previously been associated with hostility (12).
Whereas previous studies have looked at the relationship between hostility and metabolic parameters in relatively restricted populations, our study used a subject pool composed of both men and women and both black and white individuals. Our results suggest that the relationship of hostility to several different parameters of glucose metabolism is different in men and women and in African-American and Caucasian subjects. Hostility was significantly related to fasting glucose in African-Americans and to fasting insulin in women and in Caucasians. This supports the findings of previous investigations that hostility related to fasting insulin was found only in Caucasian subjects (16,20). As in one previous study, the relationship of hostility to fasting insulin seemed to be at least partially dependent on BMI in Caucasians (20). Our data also suggest that hostility, as measured by the CMHOST, is negatively related to insulin sensitivity in women and Caucasians in general but that this relationship is partially mediated by BMI. However, in African-Americans, hostility is strongly positively related to fasting glucose and not to fasting insulin. Furthermore, this relationship is robust and cannot be accounted for by BMI. Therefore, hostility may be an important and independent risk factor for diabetes in the African-American population. Although we did not find an interaction between race and gender, our sample size may not have been large enough to detect one if it had been present.
Several explanations of how hostility can affect health have been conceptualized: a health behavior model, a constitutional vulnerability model, and a stress moderation model (15). The health behavior model suggests that hostility is associated with high-risk behaviors that subsequently contribute to onset of disease. This model may explain, at least in part, the relationship between hostility, fasting insulin, and insulin sensitivity in Caucasians, because these relationships seem to be mediated, at least in part, by BMI. BMI is associated with many behaviors, such as caloric intake and exercise habits, and is known to be independently related to hostility (12,13). However, because taking BMI into account does not affect the relationship of hostility to fasting glucose that we observed in African-Americans, the relevance of the health behavior model is less apparent in this group. The constitutional vulnerability hypothesis suggests that both hostility and illness are products of underlying third variables. The stress moderation model proposes that, relative to individuals low in hostility, hostile individuals display heightened neuroendocrine reactivity in response to stress. Furthermore, an extension of this model proposes that hostile individuals also experience more stress because they interpret their environments as threatening and tend to engage in conflictive social interactions. Consistent with this model, hostility has been linked to increases in the activity of the hypothalamic-pituitary-adrenal axis (42,43). Cortisol, a product of adrenal cortical activity, is a major neuroendocrine mediator of hepatic glucose production, whereas sympathetic neural input to the pancreas can inhibit insulin secretion (44). There is some evidence that cortisol responsivity may be related to hostility. Investigations of individuals with high levels of hostility have shown that they exhibit greater diurnal cortisol fluctuations (15) and poorer recovery after exposure to stressful circumstances (42,43). Therefore, individuals high in hostility may exhibit greater cortisol and catecholamine elevations in response to stress and a slower return to baseline cortisol levels. Increases in circulating cortisol can mediate an increase in hepatic glucose production, and at the same time, increases in norepinephrine levels can limit the ability of the pancreas to secrete insulin. As noted above, hostility is positively correlated to fasting glucose but not to fasting insulin in African-Americans, suggesting that hepatic glucose is elevated and that pancreatic function is relatively compromised in African-Americans with high levels of hostility. Therefore, the psychophysiological reactivity model of how hostility affects health could be more relevant for this population. It is also possible that certain groups, such as African-Americans, might be both more metabolically vulnerable to stress as well as more exposed to stressful environmental stimuli. This might help explain the racial disparity in diabetes observed in this ethnic group. Further research incorporating a direct test of this hypothesis is required.
Hyperglycemia associated with diabetes has long been known to increase risk of CAD, but more recent studies have shown that this relationship exists in nondiabetic individuals as well. Fasting glucose (21,27,29), fasting insulin (21,28), and average blood glucose as measured by HbA1c (32,33) have all been related to risk of CAD. In addition, both fasting glucose and insulin have been shown to be related to cardiac vagal tone, which is a risk factor for cardiac death (45). Average blood glucose as measured by HbA1c has been related to increased risk of death from cardiovascular disease and from all-cause mortality as well (33). HbA1c values are normally distributed in the population. Men with HbA1c values in the highest quartile of the nondiabetic population have 2.5 times the relative risk of death from cardiovascular disease compared with individuals in the lowest quartile. Given this relationship between levels of blood glucose and risk for cardiovascular disease, the strong relationships found between hostility and variations in glucose metabolism suggest that glucose metabolism may mediate the relationship between hostility and CAD. Fasting blood glucose, fasting insulin, and insulin sensitivity have been shown to be risk factors for development of type 2 diabetes (46,47) as well as for CAD.
In summary, this study supports previous findings in which hostility has been related to hyperinsulinemia and insulin sensitivity in women and in Caucasian populations. Furthermore, our data show that hostility is strongly related to fasting glucose in African-Americans. Given that multiple parameters of glucose metabolism have been shown to be risk factors for development of cardiovascular disease, the results of the present study suggest that the relationship of hostility to cardiovascular disease may be mediated, in part, by impaired glucose metabolism. Because higher levels of fasting glucose and fasting insulin as well as decreased insulin sensitivity are risk factors for type 2 diabetes, hostility may also be a risk factor for diabetes. Data from the present study suggest that the relationship of hostility to glucose metabolism is mediated differently in Caucasian and African-American populations. Because little is known about differences in the pathophysiology of type 2 diabetes in these ethnic groups, further study of these differences may contribute to understanding the mechanisms of the significant racial disparity in the prevalence of diabetes in African-Americans.
This research was supported by National Institute of Diabetes and Digestive and Kidney Diseases Grant R01-DK-57841 to R.S.S.; by National Heart, Lung, and Blood Institute Grant P01-HL-36587 to R.B.W.; by National Heart, Lung, and Blood Institute Grant R01-HL-54780 to J.C.B.; by National Heart, Lung, and Blood Institute Grant R01-HL-55356 and National Institute on Aging Grant R01-AG-12458 to I.C.S.; and by National Institutes of Health Grant M01-RR-30 (Clinical Research, NCRR).
Address correspondence and reprint requests to Dr. Richard S. Surwit, Duke University Medical Center, Box 3842, Durham, NC 27710. E-mail:.
Received for publication 24 September 2001 and accepted in revised form 15 January 2002.
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