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Biomedical subjects

M P Stern

Publications and source records attributed to M P Stern.

At least 37 records · Page 2Linked to original sources
PubMed1999

Rapid rise in the incidence of type 2 diabetes from 1987 to 1996: results from the San Antonio Heart Study.

BACKGROUND: The prevalence of type 2 diabetes has increased in the early part of the 20th century, particularly in developing countries. There is now evidence that the prevalence also continues to increase in developed countries, including the United States. However, it is unknown whether this increase is due to a rise in the incidence of diabetes or to decreasing diabetic mortality or both. METHODS: Participants in the San Antonio Heart Study, who were nondiabetic at baseline and who returned for a 7- to 8-year follow-up examination, were examined for secular trends in the incidence of type 2 diabetes. Risk factors for diabetes, such as obesity, were also examined. Patients were enrolled in the San Antonio Heart Study from 1979 to 1988 and 7- to 8-year incidence of diabetes was determined from 1987 to 1996. RESULTS: A significant secular trend in the 7- to 8-year incidence of type 2 diabetes was observed in Mexican Americans (5.7% for participants enrolled in 1979 to 15.7% for participants enrolled in 1988). In non-Hispanic whites, the incidence increased from 2.6% for participants enrolled in 1980 to 9.4% for participants enrolled in 1988 (P = .07) . After adjusting for age and sex, the secular trend remained significant in Mexican Americans and borderline significant in non-Hispanic whites. This indicates that between 1987 and 1996 the 7- to 8-year incidence of type 2 diabetes approximately tripled in both ethnic groups. The overall secular trend also remained significant after adjusting for additional risk factors for diabetes, such as obesity. A rising secular trend in obesity was also observed. CONCLUSIONS: There has been a significant increasing secular trend in the incidence of type 2 diabetes in Mexican Americans and a borderline significant trend in non-Hispanic whites participating in the San Antonio Heart Study. Unlike other cardiovascular risk factors such as lipid levels, cigarette smoking, and blood pressure, which are either declining or under progressively better medical management and control, and unlike cardiovascular mortality, which is also declining, obesity and type 2 diabetes are exhibiting increasing trends. Thus, obesity and diabetes could easily become the preeminent US public health problem.

Adult↗
PubMed1999

Diabetes and hypertension in Mexican American families: relation to cardiovascular risk.

There is a strong familial predisposition to type 2 diabetes, hypertension, and cardiovascular disease. The authors evaluated the association between a family history of these diseases and a large panel of cardiovascular risk factors in 1,431 Mexican American subjects who were enrolled in the San Antonio Family Heart Study in San Antonio, Texas. The baseline phase of the study covered 1992-1996. Diabetes and hypertension were diagnosed according to standard clinical criteria, while cardiovascular disease was defined as a history of heart attack or heart surgery. The prevalence of diabetes, hypertension, and cardiovascular disease in this population was 15%, 12%, and 3%, respectively. For each unaffected subject, the authors computed a family history score based on the presence or absence of disease in parents and older siblings, and correlations between cardiovascular risk factors and family history scores were estimated by using likelihood-based variance component methods. Diabetes family history score was significantly correlated with a broad panel of cardiovascular risk factors, including glucose and insulin, obesity, blood pressure, triglycerides, and total cholesterol. Hypertension family history score was significantly correlated with glucose, blood pressure, body mass index, waist circumference, total cholesterol, and triglycerides. These results support the idea that genes that confer a risk for diabetes, and to a lesser extent hypertension, adversely alter the cardiovascular risk profile long before the manifestation of clinical disease.

Adult↗
PubMed1999

Genetic determinants of variation in gallbladder disease in the Mexican-American population.

Since there have not been any studies that quantify the influence of genetic factors on gallbladder disease (GBD) in humans using information from families, we utilized pedigree data to explore the genetic control of variation in liability to GBD. Using an extension of a variance components approach, we performed genetic analyses of GBD using information from 32 low-income Mexican-American families with two slightly different general models incorporating several sex-specific GBD risk factors. After evaluating the relative magnitudes of the covariate effects from these two models, we identified a parsimonious model including only significant predictors of GBD. According to this model, heritability for GBD was high (h2 = 0.44+/-0.18), after accounting for the significant effects of age, leptin in both sexes, total cholesterol, and HDL cholesterol in males only. We have shown quantitatively that variation in GBD is under strong genetic control. However, there are two major limitations to our findings: (1) since GBD was defined by a self-reported clinical history rather than an ultrasound examination, the prevalence of GBD could have been underestimated; and (2) since our design did not allow for shared environmental effects, our estimate of heritability may have been inflated.

Adult↗
PubMed1999

Do Mexican Americans really have low rates of cardiovascular disease?

In this article we challenge the conclusion made from vital statistics that Hispanic Americans have lower all-cause and cardiovascular disease (CVD) mortality than non-Hispanic whites. There is reason to believe that vital statistics underascertain minority, and in particular Hispanic, deaths. Cohort studies minimize many of these limitations. In the San Antonio Heart Study risk factor distributions predicted higher all-cause and CVD mortality among Mexican Americans than among non-Hispanic whites. Follow-up of the cohort confirmed a mortality ratio of 1.38 for all-cause and 1.30 for CVD mortality for Mexican Americans vs non-Hispanic whites. This excess risk was confined to U.S.-born Mexican Americans, since immigrants from Mexico had very low mortality despite low socioeconomic status. We attribute this latter finding to a "healthy migrant effect."

Cardiovascular Diseases↗
PubMed1999

Linkage of type 2 diabetes mellitus and of age at onset to a genetic location on chromosome 10q in Mexican Americans.

Since little is known about chromosomal locations harboring type 2 diabetes-susceptibility genes, we conducted a genomewide scan for such genes in a Mexican American population. We used data from 27 low-income extended Mexican American pedigrees consisting of 440 individuals for whom genotypic data are available for 379 markers. We used a variance-components technique to conduct multipoint linkage analyses for two phenotypes: type 2 diabetes (a discrete trait) and age at onset of diabetes (a truncated quantitative trait). For the multipoint analyses, a subset of 295 markers was selected on the basis of optimal spacing and informativeness. We found significant evidence that a susceptibility locus near the marker D10S587 on chromosome 10q influences age at onset of diabetes (LOD score 3.75) and is also linked with type 2 diabetes itself (LOD score 2.88). This susceptibility locus explains 63.8%+/-9.9% (P=. 000016) of the total phenotypic variation in age at onset of diabetes and 65.7%+/-10.9% (P=.000135) of the total variation in liability to type 2 diabetes. Weaker evidence was found for linkage of diabetes and of age at onset to regions on chromosomes 3p, 4q, and 9p. In conclusion, our strongest evidence for linkage to both age at onset of diabetes and type 2 diabetes itself in the Mexican American population was for a region on chromosome 10q.

Age Factors↗
PubMed1999

Human pedigree-based quantitative-trait-locus mapping: localization of two genes influencing HDL-cholesterol metabolism.

Common disorders with genetic susceptibilities involve the action of multiple genes interacting with each other and with environmental factors, making it difficult to localize the specific genetic loci responsible. An important route to the disentangling of this complex inheritance is through the study of normal physiological variation in quantitative risk factors that may underlie liability to disease. We present an analysis of HDL-cholesterol (HDL-C), which is inversely correlated with risk of heart disease. A variety of HDL subphenotypes were analyzed, including HDL particle-size classes and the concentrations and proportions of esterified and unesterified HDL-C. Results of a complete genomic screen in large, randomly ascertained pedigrees implicated two loci, one on chromosome 8 and the other on chromosome 15, that influence a component of HDL-C-namely, unesterified HDL2a-C. Multivariate analyses of multiple HDL phenotypes and simultaneous multilocus analysis of the quantitative-trait loci identified permit further characterization of the genetic effects on HDL-C. These analyses suggest that the action of the chromosome 8 locus is specific to unesterified cholesterol levels, whereas the chromosome 15 locus appears to influence both HDL-C concentration and distribution of cholesterol among HDL particle sizes.

Adult↗
PubMed1999

Prevalence of hypertension in a Mexican population according to the Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure.

BACKGROUND: Hypertension in Mexico represents a challenging public health problem. The National Survey on Chronic Diseases published in 1993 reported that hypertension affects more than 10 million Mexicans. No information has been published regarding the prevalence of hypertension in Mexico using the new diagnostic criteria established by the Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure (JNC VI). METHODS: The Mexico City Diabetes Study is a prospective study designed to estimate the prevalence and incidence of cardiovascular risk factors in a low-income area. The survey included 941 men and 1341 non-pregnant women aged 35-64 years. Blood pressure measurements were performed using a random zero sphygmomanometer. The diagnostic criteria for hypertension were those recommended by the JNC VI. RESULTS: The crude prevalence of hypertension was 17.2% and 18.1% in men and women, respectively. We found significant associations between hypertension and obesity, body fat distribution, very-low-density lipoprotein cholesterol, fasting and 2-h post-glucose in both sexes, and between hypertension and total cholesterol, low-density lipoprotein cholesterol and triglycerides levels in women. In 40% of hypertensive men and 23% of women, hypertension was undiagnosed and untreated. Of the previously diagnosed hypertensive individuals, 38% of men and 30% of women reported not taking antihypertensive medicine. The prevalence++ of associated risk factors in this population is 12.3% for tobacco consumption, 22.4% for diabetes, 49.8% for hypertriglyceridemia and 40.9% for hypercholesterolemia. CONCLUSIONS: Hypertension occurs in 18% of this population. There is a high prevalence of undiagnosed and untreated cases. Associated cardiovascular risk factors are highly prevalent.

Adult↗
PubMed1999

Normal variation in leptin levels in associated with polymorphisms in the proopiomelanocortin gene, POMC.

We previously reported that our genome-scanning initiative had detected a highly significant linkage (log odds ratio = 4.95; P = 9 x 10(-7)) between a quantitative trait locus (QTL) on chromosome 2 and leptin levels in Mexican American families. We now have typed additional microsatellite markers in this region, increasing this log odds ratio score to 7.46 (P = 2 x 10(-9)). This region of chromosome 2 contains a strong positional candidate gene, POMC. The POMC gene codes for POMC, the prohormone from which alphaMSH, ACTH, and beta-endorphin are derived. Studies by others have shown that POMC-derived products are involved in the regulation of appetite and obesity. We have used polymorphisms in POMC to map its location within the 95% confidence interval of the peak for the linkage signal for the QTL. We also constructed POMC haplotypes using these polymorphisms and have found a significant association with normal variation in leptin levels (P = 0.001). We conclude that variation in POMC is associated with normal variation in serum leptin levels, providing further evidence that POMC may be the leptin QTL previously identified in Mexican American families.

Chromosome Mapping↗
PubMed1999

A quantitative scale of acanthosis nigricans.

OBJECTIVE: To develop and validate a scale for acanthosis nigricans (AN). RESEARCH DESIGN AND METHODS: Subjects were participants from the San Antonio Family Diabetes Study and the San Antonio Family Heart Study. A total of 406 subjects were independently examined for AN by at least two observers. Five locations were examined: the neck, axilla, elbows, knuckles, and knees. Interobserver concordance and kappa statistics were calculated to determine replicability of the scale. Comparisons of diabetes-related risk factors by AN score were also calculated. RESULTS: Only the neck had consistently high kappa statistics, and thus, other locations were excluded from further analyses. Elevated AN was strongly associated with elevated fasting insulin and BMI in both diabetic and nondiabetic subjects. Elevated AN was also strongly associated with elevated fasting glucose, systolic blood pressure, and diastolic blood pressure, and with decreased HDL in nondiabetic subjects. In diabetic subjects, elevated AN was associated with elevated total cholesterol. CONCLUSIONS: We have developed a scale for AN that is easy to use, has high interobserver reliability in Mexican Americans, and correlates well with fasting insulin and BMI. This scale will permit longitudinal and cross-sectional evaluation of AN and will permit the evaluation of AN as a trait in genetic studies.

Acanthosis Nigricans↗
PubMed1998

A paired sibling analysis of the beta-3 adrenergic receptor and obesity in Mexican Americans.

The beta3 adrenergic receptor, located on chromosome 8, is a regulator of energy expenditure and lipolysis. A missense mutation in this gene, characterized by the replacement of tryptophan by arginine at codon 64 (Trp64Arg), is associated with obesity in some studies. We examined the effect of this variant on obesity in Mexican Americans, using a paired sibling design to minimize variability due to genetic background and a previously identified major susceptibility locus for obesity. We identified 45 sib-pairs that were concordant (identical by descent) for a locus on chromosome 2 which we have shown previously to be tightly linked to obesity in this population. The Trp64Arg variant, detected by PCR-restriction fragment length polymorphism analysis, was present in one sibling within each of the 45 sib-pairs. Presence of the variant was associated with significantly higher values in body mass index (P = 0.04), fat mass (P = 0.04), and waist circumference (P = 0.05). We conclude that the Trp64Arg variant is associated with obesity in this Mexican American population. The paired sibling design probably enhanced our ability to detect the effects of this variant by allowing us to account for variation attributable to another obesity susceptibility locus and to background genes.

Adult↗
PubMed1998

Variant in sulfonylurea receptor-1 gene is associated with high insulin concentrations in non-diabetic Mexican Americans: SUR-1 gene variant and hyperinsulinemia.

The high-affinity sulfonylurea receptor (SUR1) gene regulates insulin secretion and may play a role in type 2 diabetes. A silent variant in exon 31 of SUR1 (AGG-->AGA) was detected by single-strand conformational polymorphism and genotypes were determined for 396 Mexican American subjects (289 non-diabetic). The normal and mutant alleles were designated G and A, respectively. Among non-diabetics, those with the AA genotype had higher fasting insulin values than those with the AG and GG genotypes (113.4 pmol/l for AA vs 82.8 pmol/l for AG/GG, P=0.043). Similar results were observed for 2-h insulin (849.6 pmol/l for AA vs 498.6 pmol/l for AG/GG, P=0.0003) and for the proinsulin to specific insulin ratio (0.068 for AA vs 0.056 for AG/GG, P=0.030). Specific insulin levels also differed significantly across the three genotypic classes (P=0.021). No differences in fasting glucose, body mass index, or waist circumference according to genotype were noted. Two-hour glucose was modestly higher in individuals with the AA genotype. Since we have previously reported linkage between SUR1 and hyperglycemia, the present association between a SUR1 variant and hyperinsulinemia in normal individuals from a high diabetes risk ethnic group raises the possibility of primary insulin hypersecretion as an antecedent of type 2 diabetes in at least some individuals from this population.

ATP-Binding Cassette Transporters↗