Diabetes and cardiovascular disease: a statement for healthcare professionals from the American Heart Association.
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American Heart Association↗
Biomedical subjects
B V Howard
Publications and source records attributed to B V Howard.
Insulin resistance and lipid metabolism.
The 3 major components of the dyslipidemia of insulin resistance are increased triglyceride levels, decreased high-density lipoprotein (HDL) cholesterol, and changes in the composition of low-density lipoprotein (LDL) cholesterol. Hyperinsulinemia and the central obesity that typically accompanies insulin resistance are thought to lead to overproduction of very low-density lipoprotein (VLDL) cholesterol. The result is more triglyceride-rich particles, fewer HDL particles, and more small, dense LDL. Postprandial triglyceride levels and measures of postprandial remnants also may contribute to increased coronary artery disease (CAD) risk in individuals with insulin resistance. Deficiency of lipoprotein lipase, an insulin-sensitive enzyme, might explain the abnormal levels of remnant particles in insulin resistance. The potential benefits of successful treatment of dyslipidemia are illustrated by clinical trials in patients with the dyslipidemia characteristic of insulin resistance (i.e., normal or only moderately elevated LDL, elevated VLDL, and low HDL). Both weight loss and exercise can improve insulin resistance and associated dyslipidemia. In patients with type 2 diabetes mellitus, certain antidiabetic therapies can also improve the lipid profile by improving insulin resistance.
Adult↗
Re: "Sex differences in risk factors for clinical diabetes mellitus in a general population: a 12-year follow-up of the Finnmark study".
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Adult↗
Rising tide of cardiovascular disease in American Indians. The Strong Heart Study.
BACKGROUND: Although cardiovascular disease (CVD) used to be rare among American Indians, Indian Health Service data suggest that CVD mortality rates vary greatly among American Indian communities and appear to be increasing. The Strong Heart Study was initiated to investigate CVD and its risk factors in American Indians in 13 communities in Arizona, Oklahoma, and South/North Dakota. METHODS AND RESULTS: A total of 4549 participants (1846 men and 2703 women 45 to 74 years old) who were seen at the baseline (1989 to 1991) examination were subjected to surveillance (average 4.2 years, 1991 to 1995), and 88% of those remaining alive underwent a second examination (1993 to 1995). The medical records of all participants were exhaustively reviewed to ascertain nonfatal cardiovascular events that occurred since the baseline examination or to definitively determine cause of death. CVD morbidity and mortality rates were higher in men than in women and were similar in the 3 geographic areas. Coronary heart disease (CHD) incidence rates among American Indian men and women were almost 2-fold higher than those in the Atherosclerosis Risk in Communities Study. Significant independent predictors of CVD in women were diabetes, age, obesity (inverse), LDL cholesterol, albuminuria, triglycerides, and hypertension. In men, diabetes, age, LDL cholesterol, albuminuria, and hypertension were independent predictors of CVD. CONCLUSIONS: At present, CHD rates in American Indians exceed rates in other US populations and may more often be fatal. Unlike other ethnic groups, American Indians appear to have an increasing incidence of CHD, possibly related to the high prevalence of diabetes. In the general US population, the rising prevalence of obesity and diabetes may reverse the decline in CVD death rates. Therefore, aggressive programs to control diabetes and its risk factors are needed.
Aged↗
Prevalence of peripheral arterial disease and associated risk factors in American Indians: the Strong Heart Study.
Studies of peripheral arterial disease (PAD) in minority populations provide researchers with an opportunity to evaluate PAD risk factors and disease severity under different types of conditions. Examination 1 of the Strong Heart Study (1989-1992) provided data on the prevalence of PAD and its risk factors in a sample of American Indians. Participants (N = 4,549) represented 13 tribes located in three geographically diverse centers in the Dakotas, Oklahoma, and Arizona. Participants in this epidemiologic study were aged 45-74 years; 60% were women. Using the single criterion of an ankle brachial index less than 0.9 to define PAD, the prevalence of PAD was approximately 5.3% across centers, with women having slightly higher rates than men. Factors significantly associated with PAD in univariate analyses for both men and women included age, systolic blood pressure, hemoglobin A1c level, albuminuria, fibrinogen level, fasting glucose level, prevalence of diabetes mellitus, and duration of diabetes. Multiple logistic regression analyses were used to predict PAD for women and men combined. Age, systolic blood pressure, current cigarette smoking, pack-years of smoking, albuminuria (micro- and macro-), low density lipoprotein cholesterol level, and fibrinogen level were significantly positively associated with PAD. Current alcohol consumption was significantly negatively associated with PAD. In American Indians, the association of albuminuria with PAD may equal or exceed the association of cigarette smoking with PAD.
Aged↗
How do we evaluate and utilize data on ethnic differences?
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Black or African American↗
Low-density lipoprotein particle size is inversely related to plasminogen activator inhibitor-1 levels. The Insulin Resistance Atherosclerosis Study.
High levels of plasminogen activator inhibitor-1 (PAI-1) and preponderance of small dense low-density lipoproteins (LDL) have both been associated with atherosclerotic disease and with the insulin resistance syndrome (IRS). In vitro studies have shown a stimulatory effect of various lipoproteins on PAI-1 release from different cells, including endothelial cells and adipocytes. The authors sought to investigate the relation of PAI-1 to LDL particle size in a large tri-ethnic population (n=1549) across different states of glucose tolerance. LDL size was determined by gradient gel electrophoresis, and PAI-1 was measured by a 2-site immunoassay, sensitive to free PAI-1. PAI-1 was inversely related to LDL size in the overall population (r=-0.21, P<0.0001), independent of gender and ethnicity. However, the authors found a significant interaction with glucose tolerance status (P=0.035). In univariate analysis, the association between PAI-1 and LDL size was most pronounced in subjects with normal glucose tolerance (NGT, r=-0.22, P<0.0001) and weaker in impaired glucose tolerance (IGT, r=-0.12, P=0.03) and type-2 diabetes (r=-0.10, P=0.02). After adjustment for demographic variables and metabolic variables known to influence PAI-1 levels (triglyceride and insulin sensitivity), a significant inverse relation of LDL size to PAI-1 levels was only present in NGT (P=0. 023). In subjects with IGT or overt diabetes, who usually have elevated PAI-1 levels, additional factors other than LDL size seem to contribute more importantly to PAI-1 levels. The demonstrated inverse relation of LDL size and PAI-1 levels provides one possible explanation for the atherogeneity of small dense LDL particles.
Adipose Tissue↗
LDL particle size in relation to insulin, proinsulin, and insulin sensitivity. The Insulin Resistance Atherosclerosis Study.
OBJECTIVE: LDL particles are heterogeneous in terms of size and density; small dense LDL particles are considered more atherogenic than larger LDL particles. The aim of this study was to investigate the interrelationships among LDL size, insulin, proinsulin (intact and split), and insulin sensitivity in a tri-ethnic population with varying degrees of glucose tolerance (n = 1,549) in the Insulin Resistance Atherosclerosis Study. RESEARCH DESIGN AND METHODS: Insulin sensitivity was assessed by a frequently sampled intravenous glucose tolerance test with minimal model analysis. Proinsulin levels were measured using highly sensitive assays without detectable cross-reactivity with insulin, and LDL size was determined by gradient-gel electrophoresis. RESULTS: In univariate analyses, LDL size was related to various features of the insulin resistance syndrome, including fasting insulin (r = -0.18), intact proinsulin (r = -0.24), split proinsulin (r = -0.24), the proinsulin-to-insulin ratio (r = -0.14), and insulin sensitivity (r = 0.21; all P < 0.0001). In a multivariate regression model (adjusted for age, BMI, ethnicity, and clinic), triglyceride levels (P = 0.0001), HDL cholesterol (P = 0.0001), sex (P = 0.002), and proinsulin (P = 0.01) were significantly related to LDL size. In the same model stratified by sex, LDL size was significantly inversely related to proinsulin in men (P = 0.005 and P = 0.04 after further adjustment for the glucose tolerance status), but not in women (P > 0.15). CONCLUSIONS: We found an inverse relation of proinsulin to LDL particle size in a large tri-ethnic population with varying degrees of glucose tolerance. This relation was independent of age, BMI, and triglyceride and HDL cholesterol concentrations, and was more pronounced in men than in women.
Arteriosclerosis↗
Use of the Semmes-Weinstein monofilament in the strong heart study. Risk factors for clinical neuropathy.
OBJECTIVE: We used the Semmes-Weinstein 5.07 monofilament to assess the prevalence of foot insensitivity and its relationship to potential risk factors. RESEARCH DESIGN AND METHODS: There were 3,638 American Indian participants from Arizona, North and South Dakota, and Oklahoma who attended a study clinic on two occasions: baseline and follow-up, 4 years later. Oral glucose tolerance tests were performed at the visits for those who had not previously been diagnosed as having diabetes. A total of 2,051 participants were diagnosed with diabetes before the study or at the subsequent study visits. At the follow-up visit, participants were tested for their ability to sense the 5.07 (10 g) monofilament at 10 sites of the foot. The prevalence of foot insensitivity was ascertained, and its relation to characteristics of participants was assessed in both univariate and logistic regression analyses. RESULTS: Diabetic participants had a much higher prevalence of foot insensitivity (defined as greater than or equal to five incorrect responses) than nondiabetic participants (14 vs. 5%, respectively). However, marked foot insensitivity was uncommon within the first few years of diagnosis of diabetes. Among the diabetic participants, those diagnosed before study entry had the highest prevalence of foot insensitivity. The prevalence of foot insensitivity was highest in the Arizona Indians (22 vs. 9% in the Dakotas and 8% in Oklahoma). In a logistic regression analysis, foot insensitivity was significantly and independently related to center (Arizona versus others), age, duration of diabetes, and height. CONCLUSIONS: Marked foot insensitivity is prevalent in the diabetic American Indian population, especially in Indians in Arizona; however, this insensitivity is apparently uncommon for several years after the diagnosis of diabetes. The data show that Indians with diabetes are particularly vulnerable to the risk of foot ulceration and that the diagnostic screening of diabetes may lead to better prevention of sensory neuropathy and subsequent foot ulceration.
Age Factors↗
Glycemic control in diabetic American Indians. Longitudinal data from the Strong Heart Study.
OBJECTIVE: To describe glycemic control and identify correlates of elevated HbA1c levels in diabetic American Indians participating in the Strong Heart Study, which is a longitudinal study of cardiovascular disease in American Indians in Arizona, Oklahoma, South Dakota, and North Dakota. RESEARCH DESIGN AND METHODS: This analysis is based on data from the baseline (1989-1992) and first follow-up (1994-1995) examinations of the Strong Heart Study. The 1,581 diabetic participants included in this analysis were aged 45-74 years at baseline, were diagnosed with diabetes before and at baseline, and had their HbA1c levels measured at follow-up. HbA1c was used as the index of glycemic control. Characteristics that may affect glycemic control were evaluated for cross-sectional and longitudinal relationships by analysis of covariance and multiple regression. RESULTS: There was no significant difference between median HbA1c at baseline (8.4%) and at follow-up (8.5%). Sex, age (inversely), and insulin and oral hypoglycemic agent therapy were significantly related to HbA1c levels in both the cross-sectional and longitudinal analyses. Current smoking, prior use of alcohol, and duration of diabetes were significant only for the cross-sectional data. Baseline HbA1c significantly and positively predicted HbA1c levels at follow-up. Comparison of HbA1c by therapy type shows that insulin therapy produced a significant decrease in HbA1c between the baseline and follow-up examinations. CONCLUSIONS: Glycemic control was poor among diabetic American Indians participating in the Strong Heart Study. Women, patients taking insulin or oral hypoglycemic agents, and younger individuals had the worst control of all the participants. Baseline HbA1c, and weight loss predicted worsening of control, whereas insulin therapy predicted improvement in control. Additional therapies and/or approaches are needed to improve glycemic control in this population.
Administration, Oral↗
HDL cholesterol subfractions and risk of developing type 2 diabetes among Pima Indians.
OBJECTIVE: To examine the relationships between HDL cholesterol subfractions and the incidence of type 2 diabetes and to evaluate potential sex differences in these relationships. RESEARCH DESIGN AND METHODS: Proportional hazards analyses were performed to examine the relationships between HDL subfractions and the development of type 2 diabetes in Pima Indian women and men. Results were controlled for age, BMI, systolic blood pressure, and 2-h glucose. RESULTS: Some 54 of 123 women and 25 of 50 men developed type 2 diabetes during a mean follow-up of 10 (2-19) years. For women, in separate models, high levels of total HDL, HDL2a, and HDL3 were negatively associated with incidence of type 2 diabetes; results were unchanged in models further controlled for fasting insulin level or alcohol consumption. For men, the results were inconsistent and associated with wide confidence intervals; high total HDL and HDL3 were positively associated with incidence of type 2 diabetes in models further controlled for fasting insulin level, but the risk estimates were attenuated in models further controlled for alcohol consumption. CONCLUSIONS: High levels of total HDL, HDL2a, and HDL3 were potential protective factors against type 2 diabetes in women after accounting for alcohol consumption and insulin resistance. High levels of total HDL and HDL3 were predictive of type 2 diabetes in men; the relationship in men appeared to be due to an association with alcohol consumption. The sex differences in the effects of HDL cholesterol may be related to the effects of sex hormones or lipoproteins.
Adult↗
Low fasting insulin levels in Eskimos compared to American Indians: are Eskimos less insulin resistant?
The prevalence of diabetes is relatively low among Eskimo people in contrast to that in other Native American populations. The reasons for this may be partially explained by differences in the occurrence of insulin resistance. In this report we compare fasting insulin levels, which correlate with insulin resistance, in Alaskan Eskimo subjects to those among American Indians. After adjusting for age, gender, and body mass index, and using identical laboratory methods, we found significantly lower insulin levels among Eskimo compared with Indian participants with normal glucose tolerance. Among Eskimos insulin levels increased with increasing body mass index, were higher for women than men, and did not appreciably change with age. Our data suggest that among Eskimo people insulin resistance may be less prevalent or severe than among American Indians, but that obesity is associated with increased insulin resistance. Future analyses will examine the association between insulin levels and other correlates of the insulin resistance syndrome. We hope that by further characterizing insulin resistance or sensitivity among Eskimo people, specific recommendations can be made that will lead to cardiovascular risk factor reduction.
Adult↗
Cardiovascular events and their reduction with pravastatin in diabetic and glucose-intolerant myocardial infarction survivors with average cholesterol levels: subgroup analyses in the cholesterol and recurrent events (CARE) trial. The Care Investigators.
BACKGROUND: Although diabetes is a major risk factor for coronary heart disease (CHD), little information is available on the effects of lipid lowering in diabetic patients. We determined whether lipid-lowering treatment with pravastatin prevents recurrent cardiovascular events in diabetic patients with CHD and average cholesterol levels. METHODS AND RESULTS: The Cholesterol And Recurrent Events (CARE) trial, a 5-year trial that compared the effect of pravastatin and placebo, included 586 patients (14.1%) with clinical diagnoses of diabetes. The participants with diabetes were older, more obese, and more hypertensive. The mean baseline lipid concentrations in the group with diabetes--136 mg/dL LDL cholesterol, 38 mg/dL HDL cholesterol, and 164 mg/dL triglycerides--were similar to those in the nondiabetic group. LDL cholesterol reduction by pravastatin was similar (27% and 28%) in the diabetic and nondiabetic groups, respectively. In the placebo group, the diabetic patients suffered more recurrent coronary events (CHD death, nonfatal myocardial infarction [MI], CABG, and PTCA) than did the nondiabetic patients (37% versus 25%). Pravastatin treatment reduced the absolute risk of coronary events for the diabetic and nondiabetic patients by 8.1% and 5.2% and the relative risk by 25% (P=0.05) and 23% (P<0.001), respectively. Pravastatin reduced the relative risk for revascularization procedures by 32% (P=0.04) in the diabetic patients. In the 3553 patients who were not diagnosed as diabetic, 342 had impaired fasting glucose at entry defined by the American Diabetes Association as 110 to 125 mg/dL. These nondiabetic patients with impaired fasting glucose had a higher rate of recurrent coronary events than those with normal fasting glucose (eg, 13% versus 10% for nonfatal MI). Recurrence rates tended to be lower in the pravastatin compared with placebo group (eg, -50%, P=0.05 for nonfatal MI). CONCLUSIONS: Diabetic patients and nondiabetic patients with impaired fasting glucose are at high risk of recurrent coronary events that can be substantially reduced by pravastatin treatment.
Adult↗
Relations of left ventricular mass to fat-free and adipose body mass: the strong heart study. The Strong Heart Study Investigators.
BACKGROUND: It is unclear whether increased left ventricular (LV) mass in overweight individuals is related to their adiposity or to greater fat-free mass (FFM). METHODS AND RESULTS: We compared echocardiographic LV mass to FFM and adipose body mass by bioelectric impedance and to anthropometric measurements in 3107 American Indian participants in the Strong Heart Study. In men and women, the relations of LV mass and FFM (r=0.37 and 0.38, P<0.001) were closer (P<0.05 to <0.001) than they were with adipose mass, waist/hip ratio, body mass index, systolic blood pressure, height, or height2.7. Regression analyses showed that in men LV mass had the strongest independent relation with FFM, followed by systolic blood pressure and age (all P<0.001); in women, LV mass was related to FFM more strongly than it was to systolic blood pressure, age (all P<0. 001), and diabetes (P=0.012). Adipose mass had no independent relation to LV mass. When waist/hip ratio or body mass index were substituted for adipose mass, LV mass was independently related to FFM (P<0.001) and body mass index (P=0.02) but not to waist/hip ratio in men and was independently related to FFM and waist/hip ratio (both P<0.001) but not to body mass index in women. Using 97.5 percentile gender-specific partitions for LV mass/FFM in reference individuals, we found that LV hypertrophy occurred in 20.8% of Strong Heart Study participants with hypertension, overweight, or diabetes compared with 10.5% and 16.7% by LV mass indexed for body surface area or height2.7. CONCLUSIONS: LV mass is more strongly related to FFM than to adipose mass, waist/hip ratio, body mass index, or height-based surrogates for lean body weight; LV mass/FFM criteria may increase sensitivity to detect LV hypertrophy.
Adipose Tissue↗
Association of apolipoprotein E phenotype with plasma lipoproteins in African-American and white young adults. The CARDIA Study. Coronary Artery Risk Development in Young Adults.
Apolipoprotein E phenotype (APOE phenotype) has been demonstrated to be a genetic determinant of cardiovascular disease. This atherogenicity may be a reflection of the association of APOE phenotype and plasma lipoprotein concentrations. The Coronary Artery Risk Development in Young Adults (CARDIA) Study affords the opportunity to assess the frequency of apolipoprotein E alleles in population-based samples of African Americans and whites in the United States and to compare the associations of APOE phenotype with lipoprotein and apoprotein concentrations. Data from 3,485 African-American and white men and women between the ages of 25 and 37 years who attended the fourth CARDIA Study examination in 1992-1993 were used in this analysis. African-American men and women had significantly higher frequencies of E2 and E4 phenotype and thus higher frequencies of *epsilon2 and *epsilon4 alleles (p < 0.005). Men and women of both races with APOE4 phenotype generally had higher low density lipoprotein cholesterol, apolipoprotein B, and lipoprotein(a) concentrations and lower high density lipoprotein cholesterol concentration, and individuals with APOE3 phenotype had the lowest triglyceride concentration. Major differences between African Americans and whites were observed in the distribution of APOE phenotypes and *epsilon alleles, but APOE phenotype was associated with similar differences in lipoprotein and apoprotein concentrations in both races. The data suggest that APOE phenotype may be a risk factor for cardiovascular disease in both African Americans and whites because it is associated similarly with an adverse lipoprotein profile.
Adolescent↗
Risk factor clustering in the insulin resistance syndrome. The Strong Heart Study.
The objective of this study was to examine how the major components of the insulin resistance syndrome relate to each other and to macrovascular disease in American Indians in the Strong Heart Study. The study cohort (4,228 resident tribal members 45-74 years old) underwent a personal interview and a physical examination between July 1989 and January 1992 at three centers: Arizona, Oklahoma, and North and South Dakota; blood samples were drawn and a 75-g oral glucose tolerance test was performed. Factor analysis was used to assess the clustering and interdependence of groups of insulin resistance syndrome variables. Within both diabetic and nondiabetic groups, three factors emerged. In nondiabetic participants, a cluster of glucose, body mass index, and insulin accounted for 35% (male) and 32% (female) of the total variance in all variables considered, and a cluster of systolic blood pressure and diastolic blood pressure accounted for 25% and 22% in men and women, respectively. Both clusters were positively associated with coronary heart disease but not peripheral vascular disease. In diabetic participants, the combination of systolic and diastolic blood pressures was the most important factor, but the cluster was not associated with coronary heart disease or peripheral vascular disease. A component containing high density lipoprotein cholesterol, triglycerides, and glucose had a positive association with coronary heart disease in diabetic women and with peripheral vascular disease in both sexes. The association of clusters of risk factors and their relations with coronary heart disease provide important clues that may be used in understanding the metabolic disorders associated with insulin resistance and diabetes.
Aged↗
All-cause mortality and cardiovascular disease mortality in three American Indian populations, aged 45-74 years, 1984-1988. The Strong Heart Study.
Community mortality surveillance for 1984-1988 was conducted by researchers of the Strong Heart Study, which examined the incidence, prevalence, and risk factors of cardiovascular disease in three American Indian populations, aged 45-74 years, in Arizona, Oklahoma, and South/North Dakota. All-cause and cardiovascular disease mortality rates were determined through the use of death certificate data. Cardiovascular disease deaths were confirmed by independent systematic review of medical records. In all three populations, men had higher all-cause and cardiovascular disease mortality rates than did women. Oklahoma exhibited slightly lower 5-year, age-adjusted, all-cause mortality (96/1,000) than did Arizona (107/1,000) and South/North Dakota (114/1,000). The leading cause of death among both sexes in Oklahoma and in South/North Dakota was cardiovascular disease. Diabetes mellitus led among Arizona women. The other major causes of death were cancer, liver disease including cirrhosis, and injury. When compared with the rates in each state, average annual all-cause mortality rates were higher for the American Indian populations in almost every age group. The all-cause annual mortality rates in the three Indian populations were close to rates in the US black population and higher than the rates of the entire US population and of US whites. This trend was amplified in the 45- to 64-year age group. Only in the 65- to 74-year age group did mortality rates in the Indian population approach those of the US population. Cardiovascular disease mortality rates were close to the US averages in Arizona and Oklahoma, but they were more than two times higher in South/North Dakota among those between 45 and 64 years of age. Thus, American Indians in Arizona, Oklahoma, and South/North Dakota exhibit high all-cause mortality rates. In particular, the South/North Dakota population cardiovascular disease death rate appears to present a potential target for community-based programs to intervene on known risk factors to promote healthy lifestyles.
Aged↗
Role of non-esterified fatty acids in the pathogenesis of type 2 diabetes mellitus.
Over 30 years after the original description of Randle's cycle, the mechanisms by which elevated circulating non-esterified fatty acids might be causally related to glucose intolerance in Type 2 diabetes mellitus remain uncertain. This review examines the evidence that elevated plasma NEFA can inhibit glucose-stimulated insulin secretion by pancreatic beta-cells and impair glucose- and insulin-stimulated glucose disposal by peripheral tissues. Experimental evidence beginning to examine the mechanisms of these phenomena is discussed.
Blood Glucose↗