James P. Gutai

Usefulness of sex steroid hormone levels in predicting coronary artery disease in men

The relation between sex hormone levels and subsequent risk of a major coronary event was studied in a nested case-control study among 163 men in the Multiple Risk Factor Intervention Trial who later had a major coronary event and in 163 controls. Cases and controls were matched for age, serum cholesterol level, randomization group, randomization date and clinic. Blood samples were collected at baseline before randomization and frozen at -70 degrees C. Follow-up extended over 6 to 8 years. Sixty-one patients had a nonfatal acute myocardial infarction and 102 fatal infarction. Total and free testosterone, total and free estradiol, androstenedione and estrone concentrations were measured. There were no significant differences between cases and controls for any sex hormone level. There was also no difference in the ratio of testosterone to estradiol. Controlling for other cardiovascular risk factors did not change these results. These results do not support previous case-control studies of a relation between sex hormone levels and risk of heart attack among men.

Plasma testosterone, high density lipoprotein cholesterol and other lipoprotein fractions

High density lipoprotein (HDL) cholesterol levels are strongly related to risk of heart attack. Identification of determinants of high density lipoprotein cholesterol may provide important information concerning the cause of heart disease. The relation between one possible determinant, testosterone, and high density lipoprotein cholesterol and other lipoprotein fractions was evaluated in 247 middle-aged men. The results indicate that testosterone levels (both free and total) were positively correlated with high density lipoprotein cholesterol (r = +0.24, p less than 0.01) and negatively correlated with triglycerides and very low density lipoprotein cholesterol. The association between testosterone and high density lipoprotein cholesterol could not be explained by intake of alcohol, obesity, age, smoking or physical activity. Furthermore, the relation of testosterone to HDL cholesterol was independent of the relation of testosterone to very low density lipoprotein (VLDL) cholesterol or triglycerides.

Racial Differences in Metabolic Control of Children and Adolescents With Type I Diabetes Mellitus

Objective This study evaluated racial differences in the metabolic control of children and adolescents with insulin-dependent (type I) diabetes mellitus and examined the interactive effects of race with age and sex. Research Design and Methods Data on several demographic and clinical variables were obtained for 102 black and 108 white children, including the percentage of total HbA1, age, age at diagnosis, duration of diabetes, pubertal status, insulin dose (U · kg−1 · day−1), body mass index, number of clinic visits kept and missed, number of hospitalizations for diabetic ketoacidosis (DKA) for the year, and socioeconomic status (SES). Results Black children had higher insulin dosages (P < 0.05) and lower SESs (P < 0.001) than white children. HbA1 was higher in black than white children (P < 0.01) after statistically adjusting for the effects of insulin dose, diabetes duration, and SES. With HbA1-based criteria, more black than white children were in poor and fewer in good metabolic control (P < 0.001). Older children (≥ to 13 yr) had higher HbA1 levels than younger (< 13 yr) children (P < 0.002), but there were no differences in HbA1 between males and females nor were there interactive effects of race, sex, and age-group. Black children were hospitalized for DKA more frequently than white children (P < 0.04). More black than white children missed clinic visits (P < 0.01), but they did not differ in number of visits kept. Conclusions Black youths with type I diabetes mellitus are in poorer metabolic control than white youths.

Relation between plasma high-density lipoprotein cholesterol and sex hormone concentrations in men.

High-density lipoprotein (HDL) cholesterol is inversely associated with risk of heart attack. Sex hormones have been suggested as possible factors contributing to the gender difference of coronary heart disease risk. Little is known about how endogenous sex hormone concentration might be related to HDL cholesterol. The relation was examined in 225 men participating in the Multiple Risk Factor Intervention Trial. Plasma testosterone concentration was positively correlated with HDL cholesterol and the change in testosterone concentration was also positively correlated with change in HDL cholesterol. The relation between testosterone and HDL cholesterol could not be fully explained by age, relative weight, alcohol consumption and cigarette smoking in the cross-sectional study. However, when this relation was examined longitudinally, the partial correlation between changes in testosterone and HDL cholesterol did not quite achieve statistical significance (0.05 less than p less than 0.10). The biologic process that relates HDL cholesterol to testosterone is not known. The results suggest an inverse relation between plasma estradiol concentration and low-density lipoprotein cholesterol, but no statistical significant correlation with HDL cholesterol. In addition, there was no association noted in the current research between estradiol concentrations and the known determinants of HDL cholesterol.

Serum estrone concentrations and coronary artery disease in postmenopausal women.

Little is known about the relation between serum sex hormones and either coronary heart disease or the development of atherosclerosis in women. We measured serum estrone concentrations in 87 postmenopausal women (age, 50 to 81 years) who were admitted for diagnostic cardiac catheterization. None of the women were on estrogen replacement therapy. Cases (n = 62) were defined as those women who had > or = 1 coronary artery with > or = 50% occlusion. All control subjects (n = 25) had 0% to 24% occlusion of all coronary arteries. Estrone concentrations, as measured by a combination of extraction, column chromatography, and radioimmunoassay, showed little difference between cases and control subjects. A difference of 6 pg/mL in the estrone level was not associated with a significantly increased risk of coronary artery disease (odds ratio [OR], 1.85; 95% confidence intervals [CI], 0.60, 5.2). Examination of mean estrone levels on the basis of the number of occluded vessels was also not significant. The primary predictors of coronary artery disease in this population were a history of diabetes (OR, 8.8; CI, 1.5, 51.4) and age (5-year increments; OR, 2.1; CI, 1.2, 3.8). There was also some suggestion that women who reported higher lifetime physical activity levels were at a reduced risk for developing coronary artery disease (OR, 0.18; CI, 0.05, 0.65). These preliminary results do not support the hypothesis that serum estrogens are related to coronary artery disease in older women, but these findings need to be replicated in larger populations of older women.

Epidemiologic studies of menopause: Changes in risk factors and disease

There have been important studies of changes in risk factors and psychosocial variables during peri- and postmenopause. Most of the studies have been done in whites. Studies have clearly documented changes in behavior and biological variables related to menopause. The most critical questions bear on the interrelationships between sex steroid hormone levels, life-styles, including diet, exercise, alcohol consumption, obesity, and changes in key risk factors that are associated with the major causes of morbidity and mortality among postmenopausal women. The best study designs should be longitudinal and include frequent, accurate, and reproducible measurements of biological and psychosocial variables. Importantly, studies should be done in heterogeneous populations. The most critical variables may be measures of the degree of obesity and fatness, diet, and exercise and their relationship to hormonal changes occurring during the peri- and postmenopausal period.

Predicting metabolic control in the first 5 yr after diagnosis for youths with type 1 diabetes: the role of ethnicity and family structure

Abstract:  The primary purpose of this study was to determine if there were differences in trajectories of metabolic control between African American and White youth with type 1 diabetes in the first 5 yr after diagnosis. A secondary purpose was to investigate other sociodemographic variables that often covary with race/ethnicity such as number of parents in the home and family income to determine if they predicted trajectories of metabolic control in youth with diabetes over and above the effects of ethnicity. A convenience sample of 71 youth was recruited. Multilevel modeling was used to estimate the population trajectory and to investigate the contribution of other variables. Differences in metabolic control between African American and White youth began shortly after diagnosis and continued to accelerate well beyond the point of diagnosis. However, subsequent analysis showed that deterioration in metabolic control could equally well be explained by living in a single‐parent household. At 24 months postdiagnosis, the metabolic control in youth from single‐parent families worsened almost three times as fast as that in youth from two‐parent families (0.11 vs. 0.04%/month). The difference in hemoglobin A1c level at 24 months was 1.34% (p = .007). Neither family income nor clinical variables such as child’s age, Tanner stage, or body mass index was significant predictor of metabolic control. Diabetes care providers should consider developing targeted interventions such as parent social support resources or school‐based youth monitoring programs for youth in single‐parent families.

ALPHA2-HS GLYCOPROTEIN PHENOTYPES AND QUANTITATIVE HORMONE AND BONE MEASURES IN POSTMENOPAUSAL WOMEN

SummaryIt has been suggested that inherited traits play a role in the development of osteoporosis by providing a background for the modulation of gene expression. In this study, we examine the influence of the different alleles of alpha2-HS glycoprotein (AHSG), a protein of the bone matrix, on quantitative estrogens, estrone and estradiol, and bone measures, bone area and density. Estrogens provide a protective effect against fractures in older women and were thus included in the analyses. Isoelectric focusing of AHSG from sera followed by immunoblotting was used to type 163 white post-menopausal women participating in a clinical trial of the effects of walking on bone loss. Plasma hormones were measured by a combination of extraction, column chromatography, and radioimmunoassay; bone measures on the dominant radius were determined with computerized tomography. Analysis of variance was done on estrogen and bone measures after controlling for the effects of age and body mass index. The two major alleles of AHSG result in three phenotypes, designated AHSG 1-1, AHSG 2-1, and AHSG 2-2. The AHSG 1-1 homozygote showed a decreased concentration of estradiol, the AHSG 2-2 homozygote showed an increased concentration, and the AHSG 2-1 heterozygote was intermediate (P=0.001). Estrone demonstrated a similar pattern in residual analysis although it did not reach statistical significance.

Adrenal response to physical stress and the effect of adrenocorticotropic hormone in newborn infants

Serial plasma cortisol concentrations were determined in a group of normal newborn infants during the first three days of life; similar measurements were made in neonates experiencing physical stress in the prenatal or postnatal period. No statistically significant differences between these groups were noted. The possibility that the adrenal gland of stressed neonates may be relatively insensitive to ACTH was then investigated: Intramuscular administration of 5 units of a soluble ACTH preparation to these subjects resulted in a substantial rise in cortisol concentration.

Diabetes Management and Metabolic Control in School-Age Children With Type 1 Diabetes

This study investigated the effect of mothers coping resources, cognitive resources, family stress, and demographic variables on diabetes management and the mediating role of diabetes management on metabolic control among children with diabetes. Mothers (N = 59) completed self-report measures. HbA1c was obtained from the medical records. Although cognitive resources, coping resources, and family stress accounted for 30% of the variance in diabetes management, the hypothesis of mediation was not supported. The only significant predictor of HbA1c was African American race/ethnicity. The findings identify modifiable targets for practice and highlight the increased risk for poor metabolic control for minority children.