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Biomedical subjects

S M Haffner

Publications and source records attributed to S M Haffner.

At least 91 records · Page 5Linked to original sources

Epidemiology of type 2 diabetes: risk factors.

A number of cross-sectional and prospective studies that compared the insulin sensitivity of various national and ethnic populations within the U.S. to the total U.S. population were analyzed to find possible risk factors for the development of type 2 diabetes. It was found that the risks for diabetes in African-Americans, Hispanics, and Native Americans are approximately 2, 2.5, and 5 times greater, respectively, than in Caucasians. Studies of the prevalence of type 2 diabetes in Mexican Americans and non-Hispanic whites in San Antonio showed that there is an inverse relationship between socioeconomic status and the prevalence of diabetes. It also appears that cultural effects lead to an increased incidence of obesity in these populations, which may lead to insulin resistance. Genetic factors may also be a contributing factor. A 5-year, prospective study of insulin resistance in Pima Indians showed a relationship between impaired glucose tolerance and subsequent development of type 2 diabetes. In a 7-year study in Mexican Americans, those subjects who had both high insulin secretion and impaired insulin sensitivity had a 14-fold increased risk of developing type 2 diabetes. Regardless of cultural and ethnic factors, the San Antonio Heart Study, which compared Mexican Americans and non-Hispanic whites, showed that in both groups, the strongest predictors of developing type 2 diabetes are elevated fasting insulin concentrations and low insulin secretion.

Adipose Tissue↗

Effects of diabetes and level of glycemia on all-cause and cardiovascular mortality. The San Antonio Heart Study.

OBJECTIVE: Although the level of hyperglycemia is clearly a risk factor for microvascular complications in diabetic patients, its role in macrovascular complications remains controversial. We followed 4,875 subjects (65% Mexican-American) for 7-8 years to investigate the effects of diabetes and hyperglycemia on all-cause and cardiovascular disease (CVD) mortality. These end points were also analyzed according to quartiles of baseline fasting plasma glucose among diabetic participants. RESEARCH DESIGN AND METHODS: The Cox proportional hazards model was used to estimate the relative risks (RRs) for all-cause and CVD mortality. RESULTS: Diabetes was significantly associated with increased all-cause mortality (RR [95% CI] = 2.1 [1.3-3.5] in men; 3.2 [1.9-5.4] in women) and increased CVD mortality (3.2 [1.4-7.1] in men; 8.5 [2.8-25.2] in women). Among diabetic subjects, those in quartile 4 had a 4.2-fold greater risk of all-cause mortality (P < 0.001) and a 4.7-fold greater risk of CVD mortality (P = 0.01) than those in quartiles 1 and 2 combined. After further adjustment for other potential risk factors, subjects in quartile 4 had a 4.9-fold greater risk of all-cause mortality and a 4.9-fold greater risk of CVD mortality than those in quartiles 1 and 2. In addition, hypertension, current smoking, and cholesterol > 6.2 mmol/l were significant predictors of CVD mortality using Cox models. CONCLUSIONS: We conclude that diabetes is a predictor of both all-cause and CVD mortality in the general population and that both hyperglycemia and common CVD risk factors are important predictors of all-cause and CVD mortality in diabetic subjects.

Activities of Daily Living↗

Reversion from type 2 diabetes to nondiabetic status. Influence of the 1997 American Diabetes Association criteria.

OBJECTIVE: To determine the incidence and the rate of reversion of type 2 diabetes to a nondiabetic status in the 7- to 8-year follow-up of the San Antonio Heart Study, and to determine the influence of the recent 1997 American Diabetes Association (ADA) criteria for diabetes on these rates. Individuals who revert have been problematic for those developing criteria for the diagnosis of type 2 diabetes. Few studies have addressed this issue using 1979 National Diabetes Data Group/1980 World Health Organization (WHO) criteria. RESEARCH DESIGN AND METHODS: We studied 3,682 Mexican-American and non-Hispanic white men and nonpregnant women who completed both the baseline and follow-up examination of the San Antonio Heart Study. Incidence and reversion rates were calculated using both the 1980 WHO and the 1997 ADA criteria. Risk factors for reversion were identified, and the best fitting model using multiple logistic regression was determined using both the 1980 WHO and the 1997 ADA criteria. RESULTS: Using the 1997 ADA criteria, the age-adjusted incidences of type 2 diabetes for Mexican-American men and women were 10.8 and 12.2%, respectively. For non-Hispanic white men and women, the age-adjusted incidence rates were 5.5 and 5.1%, respectively. Similar age-adjusted incidences were recorded using the 1980 WHO criteria. The reversion rate for individuals with type 2 diabetes was 11.5% using the 1980 WHO criteria and 12.5% using the 1997 ADA criteria. These rates were not significantly different. Numerous risk factors for reversion were identified. The best fitting model, after controlling for age, sex, and ethnicity, included baseline 2-h glucose level, baseline HDL cholesterol, and previous diagnosis of diabetes. The models were the same for both the 1980 WHO and the 1997 ADA criteria. CONCLUSIONS: There was no significant difference in the incidence or the reversion rates for diabetic subjects using either 1980 WHO or 1997 ADA criteria. In addition, the risk factors for reversion were very similar using either set of criteria. The revision of the ADA criteria did not have a significant influence on reversion in this study.

Adult↗

Leptin concentrations in women in the San Antonio Heart Study: effect of menopausal status and postmenopausal hormone replacement therapy.

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. Leptin concentrations are higher in women relative to men, a difference that is only partially explained by the increased fat depots in women. The authors hypothesized that higher estrogen levels in women might be responsible for the sexual dimorphism in leptin concentrations. To test this hypothesis, they measured leptin concentrations in premenopausal women not on oral contraceptives (PRE) (n = 53), postmenopausal women on hormone replacement therapy (POSTY) (n = 28), and postmenopausal women not on hormone replacement therapy (POSTN) (n = 28) in the San Antonio Heart Study, a population-based study of diabetes and cardiovascular risk factors. Analyses were restricted to nondiabetic Mexican Americans. Subjects were well matched on obesity as assessed by body mass index (kg/m2): PRE = 31.0, POSTY = 29.8, and POSTN = 31.6. Leptin concentrations (ng/ml) were not significantly different among the three groups (PRE = 27.6, POSTY = 28.3, and POSTN = 27.8). The authors conclude that differences in estrogen levels are not likely to explain the sexual dimorphism in leptin concentrations.

Body Mass Index↗

Progress in population analyses of the insulin resistance syndrome.

Insulin resistance is associated with a variety of cardiovascular risk factors including hypertension, dyslipidemia, and non-insulin-dependent diabetes. In blacks, the relation between insulin resistance, hypertension, and atherosclerosis has been questioned. Most data collected on the Insulin Resistance Syndrome have been collected in nondiabetic subjects; therefore, no inference can be drawn to exogenous insulin use in diabetic subjects where improved glycemic control is usually associated with improved cardiovascular risk factors (especially dyslipidemia) in the absence of weight gain.

Black People↗

Do high proinsulin and C-peptide levels play a role in autonomic nervous dysfunction?: Power spectral analysis in patients with non-insulin-dependent diabetes and nondiabetic subjects.

BACKGROUND: Immunoreactive insulin has been shown to predict the development of parasympathetic autonomic neuropathy. It is possible that constituents of immunoreactive insulin could explain this association. In this cross-sectional study, the relationship of specific insulin, C-peptide, and proinsulin with autonomic nervous dysfunction was evaluated in 57 NIDDM patients and 108 control subjects. METHODS AND RESULTS: The frequency-domain analysis of heart rate variability was determined by using spectral analysis from stationary regions of registrations while the subjects breathed spontaneously in a supine position. Total power was divided into three frequency bands: low (0 to 0.07 Hz), medium (MFP, 0.07 to 0.15 Hz), and high (HFP, 0.15 Hz to 0.50 multiplied by the frequency equal to the mean RR interval). In NIDDM patients, total power, the three frequency bands (P<.001 for each), and the MFP/HFP ratio (P=.016), which expresses sympathovagal balance, were reduced compared with control subjects. Fasting proinsulin (r(s)=-.324, P=.014 for diabetics and r(s)=-.286, P=.003 for control subjects), C-peptide (r(s)=-.492, P<.001 for diabetics and r(s)=-.304, P=.001 for control subjects), and total immunoreactive insulin (r(s)=-.291, P=.028 for diabetics and r(s)=-.228, P=.017 for control subjects) were inversely related to MFP/HFP. For proinsulin and C-peptide the results did not change after controlling for the effects of age, body mass index, and fasting glucose. CONCLUSIONS: Both proinsulin and C-peptide levels were significantly associated with the sympathovagal balance of autonomic nervous function in NIDDM patients and control subjects, but this study cannot determine whether these compounds are directly involved in autonomic nervous dysfunction.

Aged↗

Low insulin sensitivity is associated with clustering of cardiovascular disease risk factors.

Hyperinsulinemia is associated with multiple metabolic disorders including high triglyceride level, low high density lipoprotein (HDL) cholesterol level, hypertension, and impaired glucose tolerance (IGT). This metabolic constellation is also called the insulin resistance syndrome. All previous data on clustering of these risk factors are, however, based on insulin levels. Therefore, the authors examined the association of insulin sensitivity estimated by means of a frequently sampled intravenous glucose tolerance test and the minimal model with the number of metabolic disorders (dyslipidemia [high triglyceride level or low HDL cholesterol level or both], hypertension, and IGT according to the World Health Organization criteria). Of 153 nondiabetic subjects aged 53-61 years who had participated in a previous population-based study, 79 had no disorders, 55 had one disorder, 16 had two disorders, and 3 had three disorders. Insulin sensitivity index (S1) decreased with the increasing number of disorders (4.1, 3.5, 1.8, and 1.4 x 10(-4) min-1 microU-1 mL-1, in subjects with 0, 1, 2, and 3 disorders, respectively; p < 0.001 for trend). Similarly, fasting (7.5, 7.8, 15.3, and 22.0 microU/mL; p < 0.001) and 2-hour insulin levels (39.9, 49.0, 98.7, and 149.6 microU/mL; p < 0.001) increased by the increasing number of disorders. The relations of S1 and fasting and 2-hour insulin levels with multiple metabolic disorders were independent of sex, obesity, and body fat distribution. Furthermore, these associations were similar in men and women and in lean and obese subjects. The authors conclude that a clustering of cardiovascular disease risk factors in nondiabetic subjects is not only associated with hyperinsulinemia but also with insulin resistance.

Cardiovascular Diseases↗

Impaired glucose tolerance, insulin resistance and cardiovascular disease.

Non-insulin-dependent diabetes (NIDDM) is associated with a higher risk of cardiovascular disease (CVD) than in the non-diabetic population. The incidence of CVD is not, however, related to the severity or duration of disease in most studies, suggesting that events in the prediabetic stage can trigger CVD. Several factors have been linked to CVD, including hyperglycaemia, insulin resistance and hyperinsulinaemia. Impaired glucose tolerance (IGT), as defined by the oral glucose tolerance test, is a strong predictor of NIDDM. In addition, IGT and raised glycated haemoglobin levels are possible risk factors for CVD. Hyperinsulinaemia has been associated with increased cardiovascular risk, but this has yet to be confirmed in women. There is also evidence to link insulin resistance with increased cardiovascular risk, although the precise nature of this relationship is unclear. There are many risk factors associated with CVD that are probably working in concert in NIDDM. This makes assessment of risk posed by individual factors, such as hyperglycaemia, hyperinsulinaemia and insulin sensitivity, difficult.

Cardiovascular Diseases↗

Plasma leptin in non-diabetic Asian Indians: association with abdominal adiposity.

Plasma leptin concentrations were measured in 144 non-diabetic men and women (age 21-73 years, BMI 14.8-37.7 kg m(-2)), in fasting samples collected during a population survey for diabetes mellitus. Leptin, fasting and 2-h post-glucose load plasma concentrations of glucose and immunoreactive insulin were measured. In a subset of 50 normoglycaemic individuals, subcutaneous fat (SF) and visceral fat (VF) areas at L4-L5 level were also measured by CT. As in other populations, women had significantly higher plasma leptin concentrations than men (p < 0.001) but the values were similar in normal (NGT) and impaired glucose tolerance (IGT). Geometric mean concentrations of leptin in men and women with NGT were 4.8 and 17.7 ng ml(-1), respectively, and the corresponding values in IGT were 6.2 and 19.0 ng ml(-1). Multiple regression analysis in the total group showed that the leptin concentration (log-transformed) was strongly dependent on sex (R2 = 53.4%), BMI (R2 = 17.4%), and to a lesser degree on the 2-h plasma insulin (R2 = 2.4%) and the WHR (R2 = 0.8%). In men, the total abdominal fat showed a strong association with leptin (R2 = 49.3%) and in women the subcutaneous fat area showed a similar effect (R2 = 39.5%). It is likely that subcutaneous and not visceral fat may be a determinant of plasma leptin in Asian Indians, and the correlation between leptin and insulin resistance may be less strong than in other ethnic groups.

Abdomen↗

Waist circumference as the best predictor of noninsulin dependent diabetes mellitus (NIDDM) compared to body mass index, waist/hip ratio and other anthropometric measurements in Mexican Americans--a 7-year prospective study.

Although a number of obesity-related variables are recognized risk factors for NIDDM, few studies have addressed which one is the best predictor. A cohort of 721 Mexican Americans aged 25-64 years who were free of NIDDM at baseline were followed for an average of 7.2 years; 105 new cases of NIDDM were diagnosed. Body weight, body mass index (BMI), waist and hip circumferences, waist/hip ratio (WHR), triceps and subscapular skinfolds were all positively predictive of NIDDM independent of age and sex. There were modest to strong correlations between these anthropometric variables, however, waist circumference was the strongest predictor of NIDDM. The predictive power of a single measurement of waist circumference was at least equal to that of WHR and BMI combined. The risk of NIDDM for those in the highest quartile of waist circumference was 11 times greater than for those in the lowest quartile (95% confidence interval: 4.2-28.8). The waist-NIDDM relation was stronger in subjects with BMI < or = 27 kg/m2 (OR: 6.0 for a 1 SD difference) than in subjects with BMI > 27 kg/m2 (OR: 1.7 for a 1 SD difference). In multivariate analysis, waist circumference was the only significant predictor of NIDDM in models that included other anthropometric variables either separately or simultaneously. WHR and BMI were independent predictors of NIDDM after adjustment for each other, however, their predictive abilities disappeared after adjustment for waist circumference. The data indicate that waist is the best obesity-related predictor of NIDDM. This finding suggests that the distribution of body fat, especially abdominal localization, is a more important determinant than the total amount of body fat of the development of NIDDM in Mexican Americans.

Adult↗

Are risk factors for conversion to NIDDM similar in high and low risk populations?

Mexican Americans have an increased risk of non-insulin-dependent diabetes mellitus (NIDDM) relative to non-Hispanic whites which is only partially explained by their excess overall obesity and unfavourable body fat distribution. Non-diabetic Mexican Americans have hyperinsulinaemia and insulin resistance relative to non-Hispanic whites. We therefore hypothesized that the insulin resistance might be a more important predictor of NIDDM in high-risk populations characterized by obesity and insulin resistance, while compromised insulin secretion might be a more important risk factor for NIDDM in low-risk populations. We assessed the ability of ethnicity (Mexican American vs non-Hispanic white), age, overall adiposity (body mass index [BMI]), unfavourable body fat distribution (as assessed by waist-to-hip ratio [WHR]), glucose tolerance (impaired glucose tolerance vs normal glucose tolerance), fasting insulin and compromised insulin secretion (as assessed by increment in insulin to the increment in glucose over the first 30 min of an oral glucose tolerance test (delta I30/delta G30)) to predict future NIDDM. In the 8-year follow-up of the San Antonio Heart Study, NIDDM developed in 11.7% (107/914) of Mexican Americans and in 5.0% (18/362) of non-Hispanic whites (p < 0.001). Multivariate predictors of NIDDM by multiple logistic regression analysis included increased age, BMI, WHR, fasting insulin and impaired glucose tolerance and decreased insulin secretion. The strongest independent predictors of NIDDM were high fasting insulin and decreased insulin secretion. These risk factors predicted NIDDM equally well in high and low-risk populations.

Adult↗

Relatively more atherogenic coronary heart disease risk factors in prediabetic women than in prediabetic men.

Men with non-insulin-dependent diabetes mellitus (NIDDM) have a twofold increased risk of coronary heart disease and women with NIDDM have a fourfold increased risk. The reasons for this higher relative risk in NIDDM women than in NIDDM men is not completely understood. Since some studies suggest that duration of clinical diabetes and degree of hyperglycaemia have only a modest effect on coronary heart disease risk, we hypothesized that women who eventually convert to NIDDM might have a more atherogenic pattern of lipids and blood pressure relative to subjects who do not convert than male converters, even in the prediabetic period. We examined this issue in Mexican-American subjects in the 8-year follow-up of the San Antonio Heart Study. Seventy-nine out of 801 men converted to NIDDM compared to 133 out of 1131 women. In both men and women, conversion to NIDDM was significantly associated with increased body mass index, fasting insulin and glucose, higher triglyceride and blood pressure and lower high density lipoprotein (HDL) cholesterol. The relative differences between converters and non-converters was significantly greater for women than for men; this interaction term for gender by conversion status was statistically significant for fasting insulin, triglyceride, HDL cholesterol and diastolic blood pressure. Thus, the higher relative risk for coronary heart disease in women with NIDDM relative to men with NIDDM may be partially due to their greater burden of cardiovascular risk factors even prior to the onset of diabetes.

Adult↗

Total immunoreactive proinsulin, immunoreactive insulin and specific insulin in relation to conversion to NIDDM: the Mexico City Diabetes Study.

Although insulin resistance and decreased insulin secretion are characteristic of established non-insulin-dependent diabetes mellitus (NIDDM), which of these metabolic abnormalities is the primary determinant of NIDDM is still controversial. A disproportionate increase in the proinsulin to insulin ratio has been proposed as a marker of compromised insulin secretion. We examined the association of fasting immunoreactive insulin (which cross-reacts with proinsulin), specific insulin (which does not cross-react with proinsulin), total immunoreactive proinsulin (or insulin precursors), and the fasting proinsulin/specific insulin ratio to the risk of developing NIDDM in the 3.25-year follow-up of the Mexico City Diabetes Study. These measurements were made in 85 subjects who subsequently converted to NIDDM (prediabetic subjects) and in 85 age and gender matched subjects who remained non-diabetic at follow-up (control subjects). Immunoreactive insulin, proinsulin and the proinsulin/specific insulin ratio were significantly higher in prediabetic than in control subjects. However, the relation between specific insulin and the development of NIDDM was weaker than for proinsulin or immunoreactive insulin. After further adjustment for obesity, body fat distribution and glucose tolerance status, proinsulin and the proinsulin/specific insulin ratio, but not specific or immunoreactive insulin, predicted conversion to NIDDM. A high proinsulin/specific insulin ratio predicted conversion to NIDDM both in subjects with normal and those with impaired glucose tolerance at baseline. We conclude that in prediabetic subjects increased proinsulin, a marker of islet cell distress or compromised insulin secretion, is associated with rapid conversion (within 3.25 years) to NIDDM even in obese populations.

Adult↗

Impaired glucose tolerance--is it relevant for cardiovascular disease?

Although IGT is clearly associated with increased cardiovascular risk factors, there is currently conflicting data regarding the association of IGT with cardiovascular disease. This is true particularly for stronger study designs, namely prospective studies. This is partly because of the relatively few studies instituted since the WHO IGT criteria were developed [1] but also because there may be uncertainty about whether other risk factors such as blood pressure or dyslipidaemia should be controlled for. If one believes that IGT (that is mildly elevated glucose levels) is responsible for increased cardiovascular risk factors, then multivariate adjustment should not be done. Furthermore, the high variability of the oral glucose tolerance test needs to be taken into account. Lastly, if IGT is a risk factor for CHD, it is not clear that the increased risk of CHD is restricted solely to those IGT subjects who convert to NIDDM.

Cardiovascular Diseases↗

Insulin resistance implications for type II diabetes mellitus and coronary heart disease.

PURPOSE: To review information on the implications of insulin resistance for type II diabetes mellitus (non-insulin-dependent diabetes mellitus) and coronary heart disease, and to derive guidance from this information for the management of these conditions. DATA SOURCES: A MEDLINE search of English-language articles published between 1985 and July 1996, and review of the bibliographies of articles obtained through the MEDLINE search and textbooks. STUDY SELECTION: Primary research articles, reviews and perspectives on the epidemiology of diabetes and cardiovascular diseases and on intervention outcomes in these diseases. DATA EXTRACTION: Study design and quality were assessed, with particular attention to methods, study population size and other characteristics. Conclusions of review articles and perspectives were analyzed critically. DATA SYNTHESIS: Type II diabetes is associated with a two- to fourfold excess of coronary heart disease, compared to nondiabetic populations. In most studies, glycemia and duration of clinical diabetes were found to be only weak risk factors for coronary heart disease. Conventional coronary heart disease risk factors such as dyslipidemia and hypertension have been associated with coronary heart disease in type II diabetes subjects. Hyperinsulinemia and insulin resistance have been predictive of the development of type II diabetes and, in some studies, of coronary heart disease. CONCLUSION: Strategies to prevent the development of coronary heart disease in diabetic and possibly prediabetic subjects should emphasize a multifactorial approach, including: a) improved glycemic control; b) aggressive treatment of risk factors for coronary heart disease, including insulin resistance; c) primary prevention of NIDDM; and d) use of glucose lowering agents that improve insulin sensitivity and cardiovascular risk factors.

Coronary Disease↗

Quantitative genetics of serum sex hormone-binding globulin levels in participants in the San Antonio Family Heart Study.

Sex hormone-binding globulin (SHBG) is a steroid-binding plasma protein with a high affinity for testosterone that has been inversely associated with cardiovascular disease risk in many populations. SHBG may also act as a receptor in some tissues. Although the function of SHBG is relatively well understood, comparatively little is known about genetic factors contributing to the normal variation of serum SHBG levels. We estimated the heritability (h2) of serum SHBG levels in 717 related Mexican-Americans participating in the San Antonio Family Heart Study (SAFHS). We found a significant heritability (h2 = 0.31, P < .0001) for serum SHBG levels; age, exogenous hormones, smoking status, diabetic status, and adiposity showed significant associations (P < .05) with mean levels of SHBG. Sex was associated with mean SHBG levels but not with genetic or environmental variance in SHBG levels; heritability estimates were the same for males and females. These results indicate a significant genetic influence on SHBG in Mexican-Americans. Thus, SHBG may prove to be an important indicator of genetic risk for cardiovascular disease in this population, as well as others.

Adolescent↗

Risk of noninsulin dependent diabetes mellitus conferred by obesity and central adiposity in different ethnic groups: a comparative analysis between Asian Indians, Mexican Americans and Whites.

Epidemiological data from Asian Indians from Madras (AI) and Mexican Americans (MA) and non-Hispanic Whites (NHW) from San Antonio heart study were compared to determine the possible contributions by the anthropometric measurements to the varied prevalence of noninsulin dependent diabetes mellitus (NIDDM) in these ethnic groups. MA had the highest rate of obesity (mean body mass index (BMI) 28.9 +/- 5.9 kg/m2) and the highest prevalence of diabetes (men 19.6%; women 11.8%, P < 0.001 vs other groups). NHW although had high rates of obesity (mean BMI 26.2 +/- 5.2 kg/m2) had low prevalence of diabetes (men 4.4%; women 5.7%) than the AI (men 9.9%; women 5.7%) (Mean BMI 22.3 +/- 4.4 kg/m2, P < 0.001). Although AI had lower BMI than MA, the risk conferred by BMI was similarly high in AI and MA and both the ethnic groups had higher risks than NHW. Impaired glucose tolerance (IGT) was also more prevalent in MA than in AI (men, MA vs AI, 11.8 vs 7.5%, P < 0.003; women 16.1 vs 5.5%, P < 0.001). NHW had lower prevalence of IGT in men (5.7%) and women (6.3%) which were significantly lower (P < 0.001) compared to MA only. Age and BMI were predictive factors of NIDDM in all, while waist to hip ratio (WHR) was significant only in AI and MA, although NHW had high WHR. This may be an indicator of differences in genetic susceptibility. This study also highlights the similarity in risk factors between AI and MA living in urban environment and the significance of distribution of adiposity in the comparatively lean AI.

Adult↗