Biomedical subjects

S M Haffner

Publications and source records attributed to S M Haffner.

At least 163 records · Page 9Linked to original sources

PubMed1995

Relation of sex hormones and dehydroepiandrosterone sulfate (DHEA-SO4) to cardiovascular risk factors in postmenopausal women.

Sex hormones play a major role in determining the risk of cardiovascular disease. While several studies have shown that reduced sex hormone-binding globulin is associated with an atherogenic pattern of lipoproteins and increased glucose concentrations in premenopausal women, little data are available examining the association of sex hormone-binding globulin and sex hormones with cardiovascular risk factors in postmenopausal women, a group with high rates of cardiovascular disease. The investigators hypothesized that in postmenopausal women decreased sex hormone-binding globulin and increased testosterone would be associated with an atherogenic pattern of cardiovascular risk factors. The sex hormone-binding globulin, total and free testosterone, estrone, and dehydroepiandrosterone sulfate (DHEA-SO4) in 253 postmenopausal women who were not taking hormones were measured in a population-based study, the Beaver Dam Eye Study (Beaver Dam, Wisconsin, 1988-1990). Sex hormone-binding globulin was significantly inversely correlated with body mass index (r = -0.53, p 0.001), glycosylated hemoglobin (r = -0.34, p < 0.001), and diastolic blood pressure (r = -0.25, p < 0.001), and positively correlated with high density lipoprotein cholesterol (HDL cholesterol) (r = 0.31, p < 0.001), and HDL cholesterol/total cholesterol (r = 0.31, p < 0.001). Total (r = -0.20, p < 0.01) and free (r = -0.14, p < 0.05) testosterone were significantly inversely correlated with HDL cholesterol/total cholesterol ratio. Total testosterone concentrations were also significantly positively correlated with total cholesterol (r = 0.15), body mass index (r = 0.16), and systolic (r = 0.17) and diastolic (r = 0.18) blood pressures (all p < 0.01). DHEA-SO4 was not associated with any of the metabolic variables, while estrone was inversely associated only with the HDL cholesterol/total cholesterol ratio (r = 0.13, p < 0.05). The authors conclude that increased androgenization in postmenopausal women is associated with atherogenic changes in cardiovascular risk factors.

Adult↗

PubMed1995

Prospective study of small LDLs as a risk factor for non-insulin dependent diabetes mellitus in elderly men and women.

BACKGROUND: The excess risk of atherosclerosis among patients with non-insulin dependent diabetes mellitus (NIDDM) is well documented. However, the presence of conventional risk factors cannot fully account for this excess risk, and the underlying mechanism remains to be elucidated. The present study prospectively evaluated the role of small LDL, a known risk factor for coronary heart disease, as a risk factor for the development of NIDDM. METHODS AND RESULTS: The study was based on a nested case-control sample of 204 elderly men and women from Kuopio, Finland. LDL subclasses were characterized by size with 2% to 14% polyacrylamide gels produced by recently developed methods. Logistic regression analysis showed that subjects with a predominance of small LDL (LDL subclass phenotype B) had a greater than two fold increased risk for developing NIDDM over the 3.5-year follow-up period. This association was independent of age, sex, glucose intolerance, and body mass index but was not independent of fasting triglyceride or insulin levels. Further, an increase of 5A in LDL diameter was associated with a 16% decrease in risk of NIDDM, and a composite variable of LDL diameter and triglyceride and HDL cholesterol concentrations, identified by principal-components analysis, was also associated with NIDDM. These associations may be attributable to the role of small LDL as a marker for insulin resistance. CONCLUSIONS: This study is the first to demonstrate that a predominance of small LDL particles is a risk factor for the future development of NIDDM, and it implies that small LDL contributes to risk of coronary heart disease in prediabetics.

Aged↗

PubMed1995

Endogenous sex hormones: impact on lipids, lipoproteins, and insulin.

Estrogen use has been reported to decrease triglyceride and low-density lipoprotein cholesterol (LDL-C) and increase high-density lipoprotein cholesterol (HDL-C). Estrogen use increases the secretion of large, very low-density lipoprotein cholesterol (VLDL-C) and also stimulates the uptake of VLDL-C by the liver and increases the catabolism of LDL-C in the liver. Sex hormones may affect several enzymes involved in the metabolism of HDL-C and triglyceride and may also affect lipolysis. In both pre- and postmenopausal women, several studies have shown that increased glucose and insulin concentrations are associated with increased free testosterone and decreased sex hormone binding globulin. The temporal direction of this relationship in premenopausal women is not clear, however. In contrast to women, increased androgen concentrations in men do not seem to be associated with increased cardiovascular risk factors, although testosterone concentrations are associated with increased HDL-C and decreased insulin concentrations. Dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) appear to be associated with improved cardiovascular risk factors in men, but this connection in women is less clear.

Androgens↗

PubMed1995

Differential impact of obesity in related populations.

To search for genetic and environmental determinants of obesity, we compared the prevalences and the impact of obesity in three populations from two cities: Mexican Americans (n = 820) and non-Hispanic whites (n = 1112) from San Antonio, Texas, and Mexicans from Mexico City (n = 1878). In the age range examined, 35-64 years, only Mexican men and women showed a significant increase in the prevalence of obesity with age. On the other hand, genetic ancestry, especially in women, made significant differences in the rates of obesity. Mexican Americans showed relatively high, and non-Hispanic whites low, rates of obesity. To discriminate between genetic and environmental influences mediating the impact of obesity on a set of hemodynamic and metabolic variables, we compared this impact between Mexican Americans and both non-Hispanic whites (same macro-environment, different gene pools), and Mexicans (same gene pool, different environments). We found that obesity always worsens the hemodynamic and metabolic profiles of individuals, but the magnitude of the effects may be variable. We showed that the levels of insulin concentrations for a given level of obesity were similar in Mexicans and Mexican Americans, suggesting that genetic influences predominate in determining insulin levels; the levels of triglycerides and HDL for a given level of obesity were similar in Mexican Americans and non-Hispanic whites, suggesting predominant environmental influences on lipid levels. On the other hand, the levels of glucose and systolic blood pressure for a given level of obesity were usually different between Mexican Americans and either of the other two populations, suggesting that these levels may result from genotype-by-environment interactions.

Adult↗

PubMed1995

A preponderance of small dense LDL is associated with specific insulin, proinsulin and the components of the insulin resistance syndrome in non-diabetic subjects.

Recently, the presence of small dense low density lipoprotein (LDL) has been postulated to be a stronger risk factor for coronary heart disease than large LDL. While small dense LDL has been associated with individual components of the insulin resistance syndrome such as hypertension, high triglyceride level, low high density (HDL) cholesterol, and diabetes mellitus, there has been little work exploring whether LDL size is decreased in subjects with multiple metabolic disorders. We examined the association of LDL size and pattern to specific insulin (which does not cross-react with proinsulin), proinsulin, increased triglyceride, decreased HDL, hypertension and impaired glucose tolerance in 488 non-diabetic subjects from the San Antonio Heart Study. LDL size was significantly related to specific insulin, proinsulin and the fasting proinsulin/insulin ratio. Small dense LDL was significantly associated with high triglyceride level, decreased HDL cholesterol, hypertension and impaired glucose tolerance. LDL size (A) decreased in a stepwise fashion with increasing number of the metabolic disorders described above (zero 262.6 +/- 9.4; one 257.0 +/- 9.3; two 256.4 +/- 9.4; three 249.0 +/- 9.1; and four 244.9 +/- 9.0). These results were similar in men and women and in non-Hispanic whites and Mexican Americans. The association between LDL size and the number of metabolic disorders remained statistically significant even after adjustment for obesity, body fat distribution, gender, ethnicity, proinsulin and insulin concentrations. Furthermore, decreases in LDL size are also significantly associated with both a selective beta-cell defect (as estimated by the fasting proinsulin/insulin ratio) and insulin resistance (as estimated by the fasting insulin concentrations) although the association was somewhat stronger for the latter. We conclude that small dense LDL may form part of the insulin resistance syndrome in non-diabetic subjects.

Diabetes Mellitus↗

PubMed1995

Serum proinsulin levels are disproportionately increased in elderly prediabetic subjects.

Insulin resistance and impaired insulin secretion are thought to be the primary defects in the pathogenesis of non-insulin-dependent diabetes mellitus (NIDDM). Disproportionately increased proinsulin relative to insulin levels are suggested to be an early indicator of a failing pancreas. We examined the relationship of fasting specific insulin, proinsulin, and 32, 33 split proinsulin concentrations, and the proinsulin: insulin ration to the risk of developing NIDDM 3.5 years later in 65-74-year-old non-diabetic Finnish subjects participating in a population-based study (n=892) on diabetes and heart disease. Altogether 69 subjects developed NIDDM over a 3.5-year follow-up (cases). The cases were compared to randomly-selected gender-matched control subjects (n=69) and control subjects matched for gender, glucose tolerance status (normal or impaired), and body mass index (n=69). There were no differences in insulin concentrations between cases and random or matched control subjects [median and interquartile range: 123 (77-154), 108 (74-143), 118 (83-145) pmol/l, p=0.271]. Random control subjects had lower proinsulin and 32, 33 split proinsulin concentrations and split proinsulin: insulin ratios compared to cases [5.7 (3.8-9.0) vs 7.3 (4.8-10.0) pmol/l, p=0.005; 7.3 (4.5-13.0 vs 10.4 (7.1-18.0) pmol/l, p=0.002; 0.073 (0.057-0.110) vs 0.097 (0.060- 0.135), p=0.003]. Matched control subjects had lower proinsulin concentrations and proinsulin: insulin ratios compared to cases [5.9 (4.0-7.7) vs 7.3 (4.8-10.0) pmol/l, p=0.019; 0.048 (0.035-0.071) vs 0.064 (0.045-0.100), p=0.008]. When cases were compared to matched control subjects a 1 SD increase in baseline proinsulin: insulin ratio was associated with a 1.37-fold risk (p=0.020) of developing diabetes. Moreover, this association was independent of fasting glucose concentration at baseline. Thus, in elderly prediabetic subjects disproportionately increased proinsulin concentration, an indicator of defective insulin secretion, is associated with conversion to diabetes over a short time period.

Aged↗

PubMed1995

Risk factors for non-insulin-dependent diabetes mellitus.

UNLABELLED: RISK FACTORS AND PREDICTORS: The risk factors for non-insulin-dependent diabetes mellitus (NIDDM) include age, overall adiposity, an adverse body fat distribution, adverse glucose and insulin concentrations, insulin resistance and lack of physical exercise. The strongest predictors of NIDDM appear to be metabolic factors, including impaired glucose tolerance and insulin resistance. TREATMENT: Pharmacological agents that improve insulin sensitivity are being tested in multicenter clinical trials. In patients with a high risk of NIDDM, it seems prudent to avoid the use of pharmacologic agents that increase insulin resistance.

Adipose Tissue↗

PubMed1995

Effect of diabetes on lipoprotein size.

The effects of diabetes on lipoprotein particle sizes were assessed using samples from 94 subjects with non-insulin-dependent diabetes mellitus. From a larger population of nondiabetic subjects who showed normal glucose tolerance, we selected an exact match in terms of age, sex, and menopausal status. We designed a protocol to make nondenaturing gradient gels for the resolution of LDL subfractions and generated two measures of LDL size: diameter of the predominant LDL species and proportion of LDL cholesterol (LDL-C) in particles larger than 25.5 nm (large LDL-C). Similarly, we made two measures of HDL size, large HDL cholesterol (HDL-C) and large HDL-apoAI, which represents the proportion of HDL-C and apoAI, respectively, occurring on particles larger than HDL-3. In pairwise comparisons, diabetes was associated with significantly (P < .004) smaller lipoprotein particles for all measures except large HDL-C. Each of the size measures was significantly and positively correlated with each of the others, suggesting that common metabolic mechanisms influence lipoprotein particle sizes across classes of lipoproteins. In addition, each of the size measures was correlated with a variety of measures of HDL and beta-lipoprotein concentrations, which included HDL-C, LDL-C, triglycerides, and apoAI, apoB, and apoE. We used stepwise regression analyses to select from the measures of lipoprotein concentrations those independently correlated with each of the lipoprotein size measures. After adjusting for these metabolic correlates of lipoprotein size measures, we found the effect of diabetes on lipoprotein size measures was no longer significant except for a modest effect (P = .027) on large HDL-apoAI.

Adult↗

PubMed1995

LDL size and subclass pattern in Mexico City residents and San Antonio Mexican Americans.

Recent studies suggest that a relative abundance of small dense LDL is a risk factor for coronary heart disease. We compared LDL size in Mexico City residents (n = 191) and San Antonio Mexican Americans (n = 282), two genetically similar populations that differ markedly in dietary behaviors: in Mexico City approximately 62% of calories are from carbohydrate and approximately 19% from fat, and in San Antonio approximately 40% of calories are from carbohydrate and approximately 40% from fat. Mean LDL size in Mexico City was 258.6 +/- 0.9 A, and in San Antonio, 255.9 +/- 0.6 A (P = .013). After adjustment for the higher triglyceride and lower HDL cholesterol levels (the two most important predictors of LDL size) in Mexico City, LDL size was significantly lower in San Antonio than in Mexico City by -8.33 +/- 0.84 A (P < .001). Our data suggest that the higher triglyceride concentrations in Mexico City residents that are associated with a higher carbohydrate diet may not be associated with atherogenic changes in LDL.

Adult↗

PubMed1995

Lipid and lipoprotein factors associated with variation in Lp(a) density.

To determine the facets of lipoprotein metabolism associated with variation in lipoprotein(a) [Lp(a)] density, we examined by density gradient ultracentrifugation 246 plasma samples exhibiting single apo(a) isoform band phenotypes. Estimated molecular weights of apo(a) isoforms ranged from 488 to 874 kD, and they accounted for approximately 80% of variation in Lp(a) density. After adjustment for variation in the protein composition, we found in univariate analyses that variation in residual Lp(a) density was associated with 10 different measures of lipoprotein size and concentration. Residual Lp(a) density was positively correlated with measures of apoB-containing lipoproteins and negatively correlated with measures of HDL. HDL size phenotypes were based on nondenaturing gradient gel electrophoresis fractions after staining for esterified cholesterol with Sudan black B and for apoA-I with immunoblotting methods. The HDL size variables in each case had higher correlations with residual Lp(a) density than did the HDL concentration measures. Stepwise regression analyses selected two lipoprotein variables (LDL density and HDL size) that were significantly correlated with residual Lp(a) density, and they accounted for approximately 35% of variation in density. The densities of LDL and Lp(a) were highly correlated, and additional stepwise regression analyses showed that they were similarly correlated with triglyceride concentration and with a measure of HDL size. Thus, with respect to residual Lp(a) density, the results show that small, dense Lp(a) particles are found under conditions leading also to small, dense LDL particles and to small, dense HDLs.

Adolescent↗

PubMed1995

Higher proinsulin and specific insulin are both associated with a parental history of diabetes in nondiabetic Mexican-American subjects.

Both insulin resistance and decreased insulin secretion have been hypothesized to be precursors of non-insulin-dependent diabetes. An elevated proinsulin concentration reflects abnormal proinsulin processing and could indicate abnormal insulin secretion. We examined fasting insulin (measured by a radioimmunoassay that does not cross-react with proinsulin), as a marker of insulin resistance, and proinsulin and the fasting proinsulin-to-insulin ratio, as markers of impaired proinsulin processing, in 597 nondiabetic Mexican-Americans from the San Antonio Heart Study. Fasting insulin, proinsulin, and the fasting proinsulin-to-insulin ratio were higher in subjects with a parental history of diabetes than in subjects without such a history. These differences remained statistically significant after adjustment for obesity, body fat distribution, and glucose tolerance. A parental history of diabetes in nondiabetic Mexican-Americans is associated with an increase in fasting specific insulin and a disproportionate increase in proinsulin relative to insulin. These data suggest that both increased insulin resistance and abnormal processing of proinsulin are present in offspring of parents with diabetes.

Blood Glucose↗

PubMed1995

Decreased insulin secretion and increased insulin resistance are independently related to the 7-year risk of NIDDM in Mexican-Americans.

The relative importance of insulin resistance and abnormal insulin secretion as risk factors for the development of non-insulin-dependent diabetes mellitus (NIDDM) is still controversial. Few data are available on insulin secretion as a risk factor for the development of NIDDM, especially in subjects with normal glucose tolerance. We examined the relation of fasting insulin (as a marker of insulin resistance) and the ratio of change in insulin to change in glucose during the first 30 min after glucose ingestion (delta I30/delta G30) (as a marker of insulin secretion) as predictors of the 7-year development of NIDDM in 714 initially nondiabetic Mexican-Americans. NIDDM developed in 99 subjects. The relative risk of NIDDM increased with higher quartiles of fasting insulin (quartile 1 [low], 1.0; quartile 2, 1.5; quartile 3, 2.0; and quartile 4 [high], 3.7; P < 0.0001) and lower delta I30/delta G30 (quartile 1 [low], 6.9; quartile 2, 1.9; quartile 3, 1.1; quartile 4 [high], 1.0; P < 0.001). Subjects with both increased fasting insulin and decreased delta I30/delta G30 had independent increases in NIDDM incidence (P < 0.001). Further, when we stratified subjects by baseline glucose tolerance, both increased fasting insulin and decreased delta I30/delta G30 significantly predicted NIDDM in subjects with both impaired and normal glucose tolerance at baseline. We conclude that both decreased insulin secretion (as assessed by low delta I30/delta G30) and increased insulin resistance (as assessed by fasting insulin) predict the development of NIDDM in Mexican-Americans, a group previously characterized as having hyperinsulinemia and insulin resistance.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1995

Evidence for a major gene affecting postchallenge insulin levels in Mexican-Americans.

Hyperinsulinemia, which is considered a hallmark of insulin resistance, precedes the development of non-insulin-dependent diabetes mellitus (NIDDM). Results of family and twin studies have shown that heredity influences insulin resistance and insulin levels. In Caucasian families ascertained through two or more NIDDM siblings, it has been reported that single genes with large effects, i.e., major genes, influence both fasting and 1-h postchallenge insulin levels. To determine whether a major gene affects 2-h postchallenge insulin levels in Mexican-Americans, we conducted segregation analyses using data collected on 527 pedigreed individuals from 27 families in San Antonio, TX. Probands for the families were randomly ascertained and all first-, second-, and third-degree relatives aged 16 years and older were invited to participate. Subjects received a 2-h oral glucose tolerance test, and diabetes was diagnosed according to World Health Organization criteria. We found that an autosomal dominant major gene best described the inheritance of 2-h insulin levels (ln-transformed) in these 27 families. Of the individuals in the population, 17% were homozygous for the 2-h low-insulin allele (back-transformed mean = 125 pmol/l) and 83% were heterozygous or homozygous for the 2-h high-insulin allele (back-transformed mean = 406 pmol/l). This major gene accounted for 31% of the variance in ln(2-h insulin levels) in this population. Using quantitative trait linkage analyses, we excluded tight linkage between this gene affecting 2-h insulin levels and three candidate loci for insulin levels: the insulin receptor gene, the low-density lipoprotein receptor gene, and the glucokinase gene.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1995

Insulin sensitivity and Lp(a) concentrations in normoglycemic men.

OBJECTIVE: Increased lipoprotein(a) [Lp(a)] concentrations have been recognized as a risk factor for coronary heart disease. Little data exists on the relationship of Lp(a) concentrations to insulin resistance. RESEARCH DESIGN AND METHODS: We examined insulin resistance (as determined by the euglycemic clamp) together with indirect calorimetry in relation to Lp(a) concentrations, apolipoprotein(a) [apo(a)] molecular weight, and apo(a) phenotype in 87 normoglycemic men. RESULTS: Lp(a) concentrations were significantly related to total (r = 0.225) and nonoxidative (r = 0.256) whole-body glucose disposal. These results suggest a positive but weak association between insulin sensitivity (restricted to the nonoxidative whole-body glucose disposal) and Lp(a) concentrations. However, after adjustment for apo(a) molecular weight [which accounts for some of the genetic influences on Lp(a) levels], total and nonoxidative body glucose disposal were not significantly related to Lp(a) concentrations. CONCLUSIONS: Normoglycemic insulin-resistant subjects do not have elevated Lp(a) concentrations.

Apolipoproteins↗

PubMed1995

Sex difference in lifestyle factors predictive of diabetes in Mexican-Americans.

OBJECTIVE: Little is known about the role of lifestyle factors in non-insulin-dependent diabetes mellitus (NIDDM) incidence among Mexican-Americans. Therefore, we examined whether baseline lifestyle factors predictive of 8-year NIDDM incidence differ in Mexican-American men and women. RESEARCH DESIGN AND METHODS: We studied 353 Mexican-American men and 491 Mexican-American women free of diabetes at baseline who participated in the San Antonio Heart Study follow-up. Lifestyle factors examined were body mass index (BMI), energy intake (total calories/kg), grams of alcohol consumed per week, efforts to control weight by dieting and exercise, leisure physical activity, sugar avoidance, saturated fat/cholesterol avoidance, and 24-h dietary recall assessment of total calories and percentage of calories from total carbohydrate, sucrose, and starch and from total, saturated, monounsaturated, and polyunsaturated fat. Incidence of NIDDM was regressed on lifestyle factors separately for men and women using a backward elimination procedure. RESULTS: Lifestyle factors significantly associated with NIDDM incidence differed for the two sexes. In men, leisure physical activity, was inversely associated and alcohol consumption, weight control by dieting, and BMI were positively associated with NIDDM. In women, BMI was positively associated with NIDDM and was the strongest lifestyle predictor. Sugar avoidance and leisure physical activity were also associated with increased NIDDM risk, while weight control by dieting was associated with decreased NIDDM risk. Saturated fat/cholesterol avoidance, grams of alcohol consumed per week, and energy intake were also negatively and indirectly associated with NIDDM in women by means of their direct effects on BMI. CONCLUSIONS: It may be important to tailor interventions designed to prevent NIDDM in Mexican-Americans to address sex differences in lifestyle precursors of this disease

Adult↗

PubMed1995

Plasma oxidizability in subjects with normal glucose tolerance, impaired glucose tolerance, and NIDDM.

OBJECTIVE: Several lines of evidence support an atherogenic role for oxidized low-density lipoprotein (LDL). Studies on LDL oxidation in diabetes to date have examined LDL isolated from plasma, but have failed to evaluate the other pro- and antioxidant factors present in vivo, the balance of which could be crucial in determining the susceptibility of LDL to lipid peroxidation. RESEARCH DESIGN AND METHODS: We examined the oxidizability of plasma from Mexican-Americans in the San Antonio Heart Study. The oxidizability of plasma in 75 subjects with normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and non-insulin-dependent diabetes mellitus (NIDDM) was studied after co-incubation with a free radical initiator, 2,2'-azobis-2-amidinopropane hydrochloride (AAPH). Lipid peroxide (LPO) levels were measured by a modified fluorimetric assay. RESULTS: Baseline LPO levels (mumol/l; means +/- SE) were similar in the three glucose tolerance categories (NGT, 1.99 +/- 0.07; IGT, 1.88 +/- 0.07; NIDDM, 1.97 +/- 0.07; P = 0.521). However, after incubation with AAPH (NGT, 4.30 +/- 0.20; IGT, 4.45 +/- 0.20; NIDDM, 5.35 +/- 0.20; P = 0.003), the diabetic plasma had significantly greater amounts of LPOs compared with the other two groups. There was no significant difference in LPOs between the NGT and IGT groups. The statistical significance of increased oxidizability of the diabetic plasma persisted after exclusion of patients who smoked cigarettes (n = 15) or who had vascular disease (n = 4). CONCLUSIONS: In conclusion, this study shows that the plasma of Mexican-American subjects with NIDDM is more prone to lipid peroxidation than that of non-Hispanic whites.

Amidines↗

PubMed1995

Apolipoprotein E polymorphism and insulin levels in a biethnic population.

OBJECTIVE: To study the association of apolipoprotein E (apoE) polymorphism with important cardiovascular risk factors other than cholesterol levels, such as insulinemia and insulin resistance. RESEARCH DESIGN AND METHODS: In this report, we study the association of three major apoE phenotypes (apoE 3/2, apoE 3/3, and apoE 4/3) with indicators of insulin resistance such as fasting insulin, glucose, and lipid levels in 320 nondiabetic Mexican-Americans and non-Hispanic whites from San Antonio, TX. RESULTS: The two ethnic groups differed in the frequencies of the three major apoE phenotypes. However, the associations of these phenotypes with lipid and insulin levels were similar in both ethnic groups and in both sexes. Compared with the other two major apoE phenotypes, the apoE 3/2 phenotype was associated with lower levels of total and low-density lipoprotein cholesterol and lower levels of fasting and 2-h postload insulin. CONCLUSIONS: In addition to the association with cholesterol levels, the variability at the apoE locus may be associated with a much broader set of metabolic factors that relate to insulin resistance.

Alleles↗

PubMed1994

Lp(a) concentrations and phenotypes in children with insulin-dependent diabetes mellitus.

Subjects with insulin-dependent diabetes mellitus (IDDM) have an increased incidence of coronary heart disease. Several studies have suggested that Lp(a) levels may be increased in IDDM subjects, although these studies have been limited by the lack of information on apo(a) phenotype and urinary albumin excretion. We compared Lp(a) concentrations in 66 children with IDDM and 18 non-diabetic children; all were non-Hispanic whites and none had detectable albuminuria. Lp(a) concentrations (mg/dl) were lower in subjects with IDDM than in non-diabetic subjects (12.0 +/- 2.2 vs. 20.0 +/- 6.1, respectively), although these means were not significantly different (P = 0.276). Postpubertal subjects, particularly males, had increased Lp(a) concentrations relative to prepubertal subjects (P = 0.041). Higher apo(a) molecular weight was associated with decreased Lp(a) concentrations in both diabetic and non-diabetic subjects. However, apo(a) size was not different in diabetic and non-diabetic subjects. Lp(a) concentrations were not significantly correlated with glycosylated hemoglobin levels in diabetic subjects (r = 0.11, P = NS). We also found similar Lp(a) concentrations in postpubertal IDDM subjects compared with adult non-Hispanic white non-diabetic subjects (n = 208) from the San Antonio Heart Study, a population-based study. These observations do not support increased Lp(a) concentrations in young normoalbuminuric IDDM subjects.

Adolescent↗