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Biomedical subjects

S M Haffner

Publications and source records attributed to S M Haffner.

At least 145 records · Page 8Linked to original sources
PubMed1996

Proteinuria predicts stroke and other atherosclerotic vascular disease events in nondiabetic and non-insulin-dependent diabetic subjects.

BACKGROUND AND PURPOSE: Increased urinary albumin and protein excretion is associated with cardiovascular disease mortality independent of other cardiovascular risk factors in subjects with non-insulin-dependent diabetes mellitus (NIDDM). We assessed the relationship between the different degrees of proteinuria at baseline and the incidence of stroke, as well as other atherosclerotic vascular disease events, in a prospective study of nondiabetic and NIDDM subjects. METHODS: Our study was based on the 7-year follow-up of cohorts of nondiabetic (n = 1375) and NIDDM (n = 1056) subjects in Finland. The urinary protein concentration at baseline was stratified into three categories: no proteinuria (< 150 mg/L), borderline (150 to 300 mg/L), and clinical proteinuria (> 300 mg/L). RESULTS: The association between the different degrees of proteinuria and the atherosclerotic vascular events was similar in nondiabetic and NIDDM subjects. Cardiovascular disease mortality was higher both in nondiabetic and NIDDM subjects with clinical proteinuria than in those without proteinuria. The incidence of stroke was 1.6% in nondiabetic subjects without proteinuria, 3.2% in subjects with borderline proteinuria, and 8.5% in subjects with clinical proteinuria (P < .001 for trend). In NIDDM patients, the corresponding rates were 7.2%, 11.1%, and 23.0%, respectively (P < .001 for trend). The association between clinical proteinuria and the incidence of stroke remained significant both in nondiabetic and in NIDDM subjects after adjustment for other cardiovascular risk factors. Clinical proteinuria was also associated with the incidence of coronary heart disease events and that of lower-extremity amputation. NIDDM independently increased the risk of atherosclerotic vascular disease events regardless of the proteinuria status. CONCLUSIONS: Clinical proteinuria significantly predicted stroke and other atherosclerotic vascular disease events independent of other cardiovascular risk factors. This finding is compatible with the view that increased urinary protein excretion rate may be associated with widespread vascular damage.

Adult↗
PubMed1996

Low levels of sex hormone-binding globulin and testosterone are associated with smaller, denser low density lipoprotein in normoglycemic men.

Recently, the phenotype with a preponderance of small, dense low density lipoprotein (LDL) has been associated with increased coronary heart disease. Although previous data indicated that decreased sex hormone-binding globulin (SHBG) and testosterone concentrations are associated with increased triglyceride and decreased high density lipoprotein (HDL) cholesterol levels in men, no data are available on the relationship of LDL composition to sex hormones. Therefore, we examined the relationship of SHBG, total and free testosterone, estradiol, and dehydroepiandrosterone sulfate to LDL size (as determined by gradient gel electrophoresis) in 87 normoglycemic men. LDL size was significantly positively related to SHBG (r = 0.354) and total testosterone (r = 0.313) and inversely related to dehydroepiandrosterone sulfate (r = -0.247), but not to free testosterone or estradiol concentrations. After adjustment for age, waist circumference, overall glucose disposal, fasting glucose, triglyceride, and HDL cholesterol, LDL size remained significantly associated with SHBG (r = 0.312) and total testosterone (r = 0.269). The relationship between LDL size and total testosterone and SHBG tended to be stronger in nonobese subjects. We conclude that SHBG and total testosterone concentrations are significantly associated with LDL size in men, and these relationships appear to be independent of known confounding variables, such as triglyceride and HDL cholesterol levels. Our data suggest that endogenous sex hormones may have an independent modifying effect on LDL composition in men.

Adult↗
PubMed1996

Genetic and environmental correlations among hormone levels and measures of body fat accumulation and topography.

In this study we partition the phenotypic correlations between body fat measures and serum levels of hormones with known, or suspected, lipolytic effects into their genetic and environmental components. Using variance decomposition techniques, we are able to estimate the pleiotropic effects of genes and/or shared environmental factors that give rise to the phenotypic correlations previously reported between these traits. We used data from a large sample of randomly ascertained Mexican-American families living in San Antonio, TX. Data were available for 582 individuals in 26 pedigrees. Levels of sex hormone-binding globulin, dehydroepiandrosterone sulfate, insulin, insulin-like growth factor I, total T4, and total T3 were assayed. The measures of body fat accumulation and topography included body mass index, subscapular/triceps ratio, and relative fat patterning index. The results of this analysis demonstrate that significant phenotypic correlations among these traits can arise from three underlying conditions: 1) entirely from shared genetic effects (pleiotropy), 2) entirely from shared random environmental effects, or 3) a combination of both effects. However, we also show that it is possible for significant genetic and environmental correlations to interact in such a way as to produce a phenotypic correlation that itself would not be considered significant.

Adipose Tissue↗
PubMed1996

Insulin secretion and resistance in nondiabetic Mexican Americans and non-Hispanic whites with a parental history of diabetes.

Both insulin resistance and decreased insulin secretion have been hypothesized as precursors of noninsulin-dependent diabetes mellitus (NIDDM). However, there are few data on insulin resistance and secretion in relationship to parental history of diabetes in ethnic groups at different risks for NIDDM. We examined the relationship of fasting insulin (as a marker of insulin resistance) and the ratio of the 30-min change in insulin to the 30-min change in glucose (delta I30/delta G30) during an oral glucose tolerance test (as a marker of insulin secretion) in relation to parental history of diabetes in 1672 nondiabetic Mexican Americans and 894 nondiabetic non-Hispanic whites. A parental history of diabetes was associated with increased fasting insulin concentrations. The association between decreased insulin secretion and parental history of diabetes was not significant. However, when insulin resistance and insulin secretion were included in the same regression model, both fasting insulin (odds ratio = 1.80; 95% confidence interval = 1.17, 2.76) and decreased insulin secretion (odds ratio = 0.70, 95% confidence interval = 0.52, 0.95) were significantly associated with a parental history of diabetes. These results were little changed after adjustment for obesity, body fat distribution, and glucose tolerance. These results were similar in both Mexican Americans and non-Hispanic whites and in both subjects with impaired and those with normal glucose tolerance. A parental history of diabetes in both Mexican Americans and non-Hispanic whites is associated with both increased fasting insulin and decreased delta I30/delta G30. These data suggest that both increased insulin resistance and early decreased insulin secretion in response to an oral glucose challenge may be important factors in the pathogenesis of NIDDM in populations at high and low risk of NIDDM. Our results also emphasize the importance of adjusting for insulin resistance in evaluating insulin secretion.

Adult↗
PubMed1996

Insulin sensitivity and abdominal obesity in African-American, Hispanic, and non-Hispanic white men and women. The Insulin Resistance and Atherosclerosis Study.

Increased abdominal obesity has been related to lower insulin sensitivity (SI), independent of overall obesity, but it has been suggested that this relationship may be weaker in non-whites. In the Insulin Resistance and Atherosclerosis Study (IRAS), SI was estimated using a minimal model analysis of the frequently sampled intravenous glucose tolerance test in 1,625 men and women aged 40-69 years. Subjects included African-Americans, Hispanics, and non-Hispanic whites from Oakland and Los Angeles, CA, San Antonio, TX, and the San Luis Valley, CO. Minimum waist circumference was significantly (P = 0.0001) associated with SI after adjusting for age, sex, height, BMI, glucose tolerance status, ethnicity, and clinic. This relationship was significantly (P = 0.0001) stronger in subjects with normal glucose tolerance (NGT) (beta = -0.030, P = 0.0001) than in those with impaired glucose tolerance (IGT) (beta = -0.010, P = 0.02; NIDDM: beta = -0.013, P = 0.0001). There were no significant ethnic differences in effect size across the spectrum of glucose tolerance. Waist circumference was also positively related to fasting insulin, an indirect measure of insulin sensitivity, in NGT (P = 0.0001), IGT (P = 0.0003), and NIDDM (P = 0.0002). The waist-fasting insulin relationship was significantly weaker in African-Americans, relative to non-Hispanic whites, in NGT and IGT (tests of statistical interaction: P = 0.04 and P = 0.02, respectively). In general, these patterns were similar in models specifying waist-to-hip ratio (WHR), rather than waist circumference, as the independent variable. While some ethnic variability exists, a negative relationship between abdominal obesity and insulin sensitivity was confirmed for all three ethnic groups across the spectrum of glucose tolerance.

Adult↗
PubMed1996

Increased insulin resistance and insulin secretion in nondiabetic African-Americans and Hispanics compared with non-Hispanic whites. The Insulin Resistance Atherosclerosis Study.

The etiology of NIDDM is still controversial, with both insulin resistance and decreased insulin secretion postulated as potential important factors. African-Americans and Hispanics have a two- to threefold excess risk of developing NIDDM compared with non-Hispanic whites. Yet little is known concerning the prevalence of insulin resistance and secretion defects in minorities, especially in African-Americans in population-based studies. Fasting and 2-h post-glucose load glucose and insulin levels, insulin-mediated glucose disposal (insulin sensitivity index) (S(I)), glucose effectiveness (S(G)), and first-phase insulin response (acute insulin response [AIR]) were determined in nondiabetic African-Americans (n= 288), Hispanics (n= 363), and non-Hispanic whites (n= 435) as part of the Insulin Resistance Atherosclerosis Study. Subjects received a standard 2-h oral glucose tolerance test on the first day and an insulin-modified frequently sampled intravenous glucose tolerance test on the second day. African-Americans and Hispanics were more obese than non-Hispanic whites. Both African-Americans and Hispanics had higher fasting and 2-h insulin concentrations and AIR but lower S(I) than non-Hispanic whites. No ethnic difference was observed in S(G). After further adjustments for obesity, body fat distribution, and behavioral factors, African-Americans continued to have higher fasting and 2-h insulin levels and AIR, but lower S(I) than non-Hispanic whites. In contrast, after adjustment for these covariates, no significant ethnic differences in S(I) or fasting insulin levels were observed between Hispanics and non-Hispanic whites. Hispanics continued to have higher 2-h insulin levels and AIRs than those in non-Hispanic whites. In this report, the association between S(I) and upper body adiposity (waist-to-hip, ratio) was similar in each ethnic group. Both nondiabetic African-Americans and Hispanics have increased insulin resistance and higher AIR than nondiabetic non-Hispanic whites, suggesting that greater insulin resistance may be in large part responsible for the higher prevalence of NIDDM in these minority groups. However, in Hispanics. the greater insulin resistance may be due to greater adiposity and other behavioral factors.

Africa↗
PubMed1996

Leptin concentrations in diabetic and nondiabetic Mexican-Americans.

Leptin, the product of the OB gene, is increased in obese individuals, suggesting resistance to its effect. We questioned whether subjects with NIDDM have an altered regulation of serum leptin levels. We used a radioimmunoassay to measure serum leptin levels in three groups from the San Antonio Heart Study: 1) 50 Mexican-Americans with NIDDM; 2) 50 nondiabetic Mexican-Americans matched by age and sex to the diabetic Mexican-Americans; and 3) 50 nondiabetic Mexican-Americans matched by age, sex, and BMI to the diabetic Mexican-Americans. Leptin concentrations did not differ significantly by diabetic status. Leptin concentrations were significantly correlated with BMI in all groups (NIDDM women: r = 0.637; nondiabetic women: r = 0.772; NIDDM men: r = 0.849; and nondiabetic men: r = 0.686; all P < 0.001). Leptin levels were higher in women than in men regardless of diabetic status. We concluded that the leptin concentrations were not different in diabetic and nondiabetic subjects and that the association of leptin with obesity was similar in diabetic and nondiabetic subjects.

Age Factors↗
PubMed1996

Nondiabetic Mexican-Americans do not have reduced insulin responses relative to nondiabetic non-Hispanic whites.

OBJECTIVE: To study why Mexican-Americans have a threefold increase in NIDDM relative to non-Hispanic whites. The etiology of NIDDM is still controversial, with both insulin resistance and decreased insulin secretion proposed as precursors of NIDDM. RESEARCH DESIGN AND METHODS: We examined possible ethnic differences in fasting insulin (as a marker of insulin resistance) and change in insulin-to-change in glucose ratio (delta I30:delta G30) during the first 30 min after oral glucose ingestion (as a marker of abnormal whites from the San Antonio Heart Study, a population-based study of diabetes and cardiovascular disease. Fasting insulin and delta I30:delta G30 were evaluated as continuous variables. RESULTS: Mexican-Americans had increased insulin concentrations at fasting and 30, 60, and 120 min after an oral glucose load as well as an increased 0- to 30-min increment in insulin and delta I30:delta G30 relative to non-Hispanic whites. These results remained unchanged after adjustment for age, sex, obesity, body fat distribution, and glucose tolerance. CONCLUSIONS: These results suggest that increased insulin resistance rather than decreased insulin secretion is characteristic of nondiabetic Mexican-Americans, a high-risk population for NIDDM.

Blood Glucose↗
PubMed1996

Sex hormones and DHEA-SO4 in relation to ischemic heart disease mortality in diabetic subjects. The Wisconsin Epidemiologic Study of Diabetic Retinopathy.

OBJECTIVE: Sex hormones are associated with atherogenic changes in lipoproteins and changes in glucose and insulin metabolism, yet few data are available on the relationship of sex hormones and dehydroepiandrosterone sulfate (DHEA-SO4) to ischemic heart disease (IHD) in diabetic subjects, a group with very high levels of IHD. RESEARCH DESIGN AND METHODS: We examined the relation of total and free testosterone, sex hormone binding globulin, estrone, estradiol, and DHEA-SO4 to the 5-year IHD mortality in the older-onset diabetic subjects in the Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR) in a matched diabetic subject-control design (two control subjects for every diabetic subject). RESULTS: In men (n = 123), none of the sex hormones or DHEA-SO4 significantly predicted IHD mortality. In women (n = 120), lower levels of DHEA-SO4 (P < 0.01) and total testosterone (P = 0.07) predicted IHD mortality. These results were essentially unchanged after adjustment for duration of diabetes, GHb, diuretic use, and serum creatinine, which are major predictors of IHD mortality in the WESDR. Finding lower testosterone levels in diabetic subjects of IHD in women is contrary to data on risk factors, which suggests that increased androgen activity may be associated with worse IHD risk factors. CONCLUSIONS: This study suggests that alterations in sex hormones and DHEA-SO4 are unlikely to explain a major proportion of the variation in IHD mortality in diabetic subjects.

Adult↗
PubMed1996

A prospective analysis of the HOMA model. The Mexico City Diabetes Study.

OBJECTIVE: Both insulin resistance (IR) and decreased insulin secretion have been shown to predict the development of NIDDM. However, methods to assess insulin sensitivity and secretion are complicated and expensive to apply in epidemiological studies. The homeostasis model assessment (HOMA) has been suggested as a method to assess IR and secretion from the fasting glucose and insulin concentrations. RESEARCH DESIGN AND METHODS: We applied the HOMA model in the 3.5-year follow-up of the Mexico City Diabetes Study. RESULTS: Out of 1,449 subjects, 97 developed diabetes. When modeled separately insulin resistance but not insulin secretion predicted NIDDM. However, when both variables were entered into the same regression model, both increased IR and decreased beta-cell function significantly predicted NIDDM. CONCLUSIONS: We conclude that the HOMA provides a useful model to assess beta-cell function in epidemiological studies and that it is important to take into account the degree of IR in assessing insulin secretion.

Adult↗
PubMed1996

Retinopathy predicts coronary heart disease events in NIDDM patients.

OBJECTIVE: Proliferative retinopathy has been shown to be associated with increased all-cause mortality in diabetic patients. We assessed the relationship between the different degrees of retinopathic changes at baseline and serious coronary heart disease (CHD) events (CHD death or nonfatal myocardial infarction) in a prospective population-based study of NIDDM patients. RESEARCH DESIGN AND METHODS: Our study is based on the 7-year follow-up cohort of 1,059 NIDDM patients in east and west Finland. Classification of retinopathic changes was based on clinical examination of fundi, and the findings were classified to three categories according to the status of the worse eye: no retinopathic changes, background retinopathy, and proliferative retinopathy. RESULTS: During the 7-year follow-up, 255 (24%) patients developed serious CHD event. In patients with proliferative retinopathy at baseline, the risk of CHD events during the follow-up was statistically significantly higher compared with patients without retinopathic changes (odds ratio [OR] 2.31, 95% CI 1.21-4.40). The association between proliferative retinopathy and CHD events remained significant when other cardiovascular risk factors were controlled for. CONCLUSIONS: Proliferative retinopathy in NIDDM patients was associated with CHD events. Our findings suggest that retinopathy and CHD may have similar pathophysiological backgrounds.

Cardiovascular Diseases↗
PubMed1996

Cardiovascular risk factors and the prediabetic syndrome.

Cardiovascular disease is increased 2- to 4-fold in non-insulin-dependent diabetes mellitus (NIDDM); yet in most studies, there is a relatively weak relationship between the frequency of coronary heart disease (CHD) and the duration of diabetes and severity of hyperglycaemia. A number of authors have suggested that the prediabetic stage may contribute to the risk of CHD in NIDDM. Hyperinsulinaemia and insulin resistance have been strongly associated with the development of NIDDM. Data are less conclusive about the relationship of hyperinsulinaemia to the development of CHD in nondiabetic subjects. Relatively little data are available on hyperinsulinaemia and/or insulin resistance to CHD in NIDDM subjects. Tight control of glycaemia with exogenous insulin improves cardiovascular risk factors in NIDDM subjects and therefore is unlikely to increase the risk of CHD. Although the relation of insulin to CHD in the general population is somewhat controversial, insulin is clearly related to multiple cardiovascular risk factors (especially elevated triglyceride, decreased high-density lipoprotein, small dense low-density lipoprotein, impaired glucose tolerance and increased plasminogen activator inhibitor 1 (PAI-1)). However, the relation of insulin resistance to hypertension remains controversial.

Coronary Disease↗
PubMed1996

Differential impact of insulin and obesity on cardiovascular risk factors in non-diabetic subjects.

OBJECTIVE: To assess the differential impact of obesity and hyperinsulinaemia on cardiovascular risk factors in non-diabetic, normotensive subjects. DESIGN: Cross-sectional (n = 1897) and 8-year follow-up data (n = 1047) from non-diabetic, normotensive, normolipidaemic men and women (screened in the San Antonio Heart Study) with a body mass index [BMI] in the range 15.2-58.5 kg/m2. RESULTS: 183 of 849 obese subjects (BMI > or = 27 kg/m2 in men, > or = 26 in women) had fasting and post-glucose plasma insulin concentrations superimposable on those of the normoinsulinaemic segment of the non-obese subgroup. Yet, waist/hip ratio (WHR), systolic and diastolic blood pressure, fasting plasma glucose and triglyceride levels were significantly higher, and serum HDL-cholesterol concentrations lower, in the obese than in the non-obese. In the whole sample (n = 1897), both obesity and hyperinsulinaemia were independently associated with higher WHR, arterial blood pressure, fasting and post-load plasma glucose and triglyceride concentrations, and lower HDL-cholesterol levels. This pattern of associations was essentially unaltered after adjustment by WHR. In the subjects re-tested 8 years following the initial screening, the 8-year changes in the level of cardiovascular risk factors were significantly associated with the corresponding changes in both fasting plasma insulin and BMI, independently of one another. CONCLUSIONS: Although plasma insulin and body weight are closely inter-related variables, they have a separate impact on the cardiovascular risk profile in normal subjects.

Adult↗
PubMed1996

Hypertension in the San Antonio Heart Study and the Mexico City Diabetes Study: clinical and metabolic correlates.

DESPITE THE GREATER OBESITY AND PREVALENCE of non-insulin-dependent diabetes mellitus (NIDDM) in Mexican Americans (MA) than in non-Hispanic whites (NHW), MA have a similar or slightly lower prevalence and incidence of hypertension than NHW. After adjustment for age, gender, obesity, and NIDDM, the prevalence of hypertension was significantly lower in MA than in NHW in both men and women. Mexican Americans, however, have lower rates of control than do non-Hispanic whites. The high rates of NIDDM, coupled with the poor control of hypertension in Mexican Americans, make efforts to control hypertension essential in this group. The prevalence of hypertension in low income residents of Mexico City is lower than in low income Mexican Americans from San Antonio, Texas.

Adult↗
PubMed1996

Leptin concentrations in relation to overall adiposity and regional body fat distribution in Mexican Americans.

OBJECTIVE: Leptin, the product of the human OB gene is increased in obese individuals suggesting resistance to its effect. However, there is variability in leptin levels at each level of body mass index suggesting that genetic and environmental factors other than overall adiposity may regulate leptin concentrations. Moreover, the relation of leptin to various adipose depots may differ. Upper body (or central adiposity) is more metabolically active than peripheral adiposity. METHODS: We examined the relation of serum leptin levels to body fat distribution in 147 non-diabetic subjects from the San Antonio Heart Study. RESULTS: Leptin concentrations in men were significantly correlated with body mass index (BMI) (r = 0.741), waist-to-hip ratio (WHR) (r = 0.567), waist circumference (r = 0.840), hips circumference (r = 0.842) triceps skinfold (r = 0.520) and subscapular skinfold (r = 0.668) but not with subscapular to triceps skinfold (r = 0.185). Leptin concentrations in women were significantly correlated with BMI (r = 0.814), WHR (r = 0.377), waist circumference (r = 0.718), hips circumference (r = 0.779), subscapular skinfolds (r = 0.636) and triceps skinfolds (r = 0.587) but not with the ratio of subscapular to triceps skinfolds (r = 0.184) in women. CONCLUSIONS: Since the associations of leptin with body mass index (a surrogate for overall adiposity), waist circumference (a surrogate for upper body) and hips circumference (a surrogate for lower body adiposity) are similar, we conclude that leptin concentrations are associated with all adipose tissue depots and not disproportionately with upper body or central adiposity.

Adipose Tissue↗