Household aggregation of Staphylococcus aureus by clonal complex and methicillin resistance profiles in Starr County, Texas.

Staphylococcus aureus is one of the most common causes of skin and soft tissue infections in health-care and community settings, but transmission of S. aureus in community-based populations is incompletely understood. S. aureus carriage phenotypes (persistent, intermittent, and non-carriers) were determined for households from Starr County, TX. Nasal swabs were collected from a cohort of 901 residents and screened for the presence of S. aureus. Isolated strains were spa-typed and assigned to clonal complexes. Of the 901 participants there were 134 pairs, 28 trios, 11 quartets, 3 quintets and 1 septet residing in the same household. There was a significant increase in "ever" carriers (persistent and intermittent carriers combined) in these households over that expected based on population frequencies (p = 0.029). There were 42 ever carrier pairs of individuals with 21 concordant for clonal complex type whereas only 4.7 were expected to be so (p = 6.9E-11). These results demonstrated clear aggregation of S. aureus carriage and concordance for strain types within households. As antibiotic-resistant S. aureus strains increase in community settings, it is important to better understand risk factors for colonization, mechanisms of transmission, clonal complexes present, and the role of household concordance/transmission.

Loci on chromosomes 2 (NIDDM1) and 15 interact to increase susceptibility to diabetes in Mexican Americans.

Complex disorders such as diabetes, cardiovascular disease, asthma, hypertension and psychiatric illnesses account for a large and disproportionate share of health care costs, but remain poorly characterized with respect to aetiology. The transmission of such disorders is complex, reflecting the actions and interactions of multiple genetic and environmental factors. Genetic analyses that allow for the simultaneous consideration of susceptibility from multiple regions may improve the ability to map genes for complex disorders, but such analyses are currently computationally intensive and narrowly focused. We describe here an approach to assessing the evidence for statistical interactions between unlinked regions that allows multipoint allele-sharing analysis to take the evidence for linkage at one region into account in assessing the evidence for linkage over the rest of the genome. Using this method, we show that the interaction of genes on chromosomes 2 (NIDDM1) and 15 (near CYP19) makes a contribution to susceptibility to type 2 diabetes in Mexican Americans from Starr County, Texas.

Genetic variation in the gene encoding calpain-10 is associated with type 2 diabetes mellitus.

Type 2 or non-insulin-dependent diabetes mellitus (NIDDM) is the most common form of diabetes worldwide, affecting approximately 4% of the world's adult population. It is multifactorial in origin with both genetic and environmental factors contributing to its development. A genome-wide screen for type 2 diabetes genes carried out in Mexican Americans localized a susceptibility gene, designated NIDDM1, to chromosome 2. Here we describe the positional cloning of a gene located in the NIDDM1 region that shows association with type 2 diabetes in Mexican Americans and a Northern European population from the Botnia region of Finland. This putative diabetes-susceptibility gene encodes a ubiquitously expressed member of the calpain-like cysteine protease family, calpain-10 (CAPN10). This finding suggests a novel pathway that may contribute to the development of type 2 diabetes.

A genome-wide search for human non-insulin-dependent (type 2) diabetes genes reveals a major susceptibility locus on chromosome 2.

Non-insulin-dependent (type 2) diabetes mellitus (NIDDM) is a common disorder of middle-aged individuals characterized by high blood glucose levels which, if untreated, can cause serious medical complications and lead to early death. Genetic factors play an important role in determining susceptibility to this disorder. However, the number of genes involved, their chromosomal location and the magnitude of their effect on NIDDM susceptibility are unknown. We have screened the human genome for susceptibility genes for NIDDM using non-and quasi-parametric linkage analysis methods in a group of Mexican American affected sib pairs. One marker, D2S125, showed significant evidence of linkage to NIDDM and appears to be a major factor affecting the development of diabetes mellitus in Mexican Americans. We propose that this locus be designated NIDDM1.

Genome-wide association and meta-analysis in populations from Starr County, Texas, and Mexico City identify type 2 diabetes susceptibility loci and enrichment for expression quantitative trait loci in top signals.

AIMS/HYPOTHESIS: We conducted genome-wide association studies (GWASs) and expression quantitative trait loci (eQTL) analyses to identify and characterise risk loci for type 2 diabetes in Mexican-Americans from Starr County, TX, USA. METHOD: Using 1.8 million directly interrogated and imputed genotypes in 837 unrelated type 2 diabetes cases and 436 normoglycaemic controls, we conducted Armitage trend tests. To improve power in this population with high disease rates, we also performed ordinal regression including an intermediate class with impaired fasting glucose and/or glucose tolerance. These analyses were followed by meta-analysis with a study of 967 type 2 diabetes cases and 343 normoglycaemic controls from Mexico City, Mexico. RESULT: The top signals (unadjusted p value <1 × 10(-5)) included 49 single nucleotide polymorphisms (SNPs) in eight gene regions (PER3, PARD3B, EPHA4, TOMM7, PTPRD, HNT [also known as RREB1], LOC729993 and IL34) and six intergenic regions. Among these was a missense polymorphism (rs10462020; Gly639Val) in the clock gene PER3, a system recently implicated in diabetes. We also report a second signal (minimum p value 1.52 × 10(-6)) within PTPRD, independent of the previously implicated SNP, in a population of Han Chinese. Top meta-analysis signals included known regions HNF1A and KCNQ1. Annotation of top association signals in both studies revealed a marked excess of trans-acting eQTL in both adipose and muscle tissues. CONCLUSIONS/INTERPRETATION: In the largest study of type 2 diabetes in Mexican populations to date, we identified modest associations of novel and previously reported SNPs. In addition, in our top signals we report significant excess of SNPs that predict transcript levels in muscle and adipose tissues.

Genome-wide association study of type 2 diabetes in a sample from Mexico City and a meta-analysis of a Mexican-American sample from Starr County, Texas.

AIMS/HYPOTHESIS: We report a genome-wide association study of type 2 diabetes in an admixed sample from Mexico City and describe the results of a meta-analysis of this study and another genome-wide scan in a Mexican-American sample from Starr County, TX, USA. The top signals observed in this meta-analysis were followed up in the Diabetes Genetics Replication and Meta-analysis Consortium (DIAGRAM) and DIAGRAM+ datasets. METHODS: We analysed 967 cases and 343 normoglycaemic controls. The samples were genotyped with the Affymetrix Genome-wide Human SNP array 5.0. Associations of genotyped and imputed markers with type 2 diabetes were tested using a missing data likelihood score test. A fixed-effects meta-analysis including 1,804 cases and 780 normoglycaemic controls was carried out by weighting the effect estimates by their inverse variances. RESULTS: In the meta-analysis of the two Hispanic studies, markers showing suggestive associations (p < 10(-5)) were identified in two known diabetes genes, HNF1A and KCNQ1, as well as in several additional regions. Meta-analysis of the two Hispanic studies and the recent DIAGRAM+ dataset identified genome-wide significant signals (p < 5 × 10(-8)) within or near the genes HNF1A and CDKN2A/CDKN2B, as well as suggestive associations in three additional regions, IGF2BP2, KCNQ1 and the previously unreported C14orf70. CONCLUSIONS/INTERPRETATION: We observed numerous regions with suggestive associations with type 2 diabetes. Some of these signals correspond to regions described in previous studies. However, many of these regions could not be replicated in the DIAGRAM datasets. It is critical to carry out additional studies in Hispanic and American Indian populations, which have a high prevalence of type 2 diabetes.

Randomised clinical trial: faecal microbiota transplantation for recurrent Clostridum difficile infection - fresh, or frozen, or lyophilised microbiota from a small pool of healthy donors delivered by colonoscopy.

BACKGROUND: Faecal microbiota transplantation (FMT) has become routine in managing recurrent C. difficile infection (CDI) refractory to antibiotics. AIM: To compare clinical response and improvements in colonic microbiota diversity in subjects with recurrent CDI using different donor product. METHODS: Seventy-two subjects with ≥3 bouts of CDI were randomised in a double-blind study to receive fresh, frozen or lyophilised FMT product via colonoscopy from 50 g of stool per treatment from eight healthy donors. Recipients provided stools pre- and 7, 14 and 30 days post-FMT for C. difficile toxin and, in a subset, microbiome composition by 16S rRNA gene profiling. RESULTS: Overall resolution of CDI was 87% during 2 months of follow-up after FMT. Stool samples before FMT had significantly decreased bacterial diversity with a high proportion of Proteobacteria compared to donors. Cure rates were highest for the group receiving fresh product seen in 25/25 (100%), lowest for the lyophilised product 16/23 (78%; P = 0.022 vs. fresh and 0.255 vs. frozen) and intermediate for frozen product 20/24 (P = 0.233 vs. fresh). Microbial diversity was reconstituted by day 7 in the subjects receiving fresh or frozen product. Improvement in diversity was seen by day 7 in those randomised to lyophilised material with reconstitution by 30 days. CONCLUSIONS: Comparative efficacy in faecal microbiota transplantation was observed in subjects receiving fresh or frozen faecal product from the same donors. The lyophilised product had a slightly lowered efficacy compared with fresh product, but it resembled other treatments in microbial restoration 1 month after faecal microbiota transplantation.

Change in level of physical activity and risk of all-cause mortality or reinfarction: The Corpus Christi Heart Project.

BACKGROUND: The role of physical activity (PA) in reducing the risk of all-cause mortality or reinfarction after a first myocardial infarction (MI) remains unresolved, particularly for minority populations. The association between change in level of PA and risk of death or reinfarction was studied in 406 Mexican American and non-Hispanic white women and men who survived a first MI. METHODS AND RESULTS: MI patients were interviewed at baseline and annually thereafter about PA, medical history, and risk factors of coronary heart disease. Change in level of PA after the index MI was categorized as (1) sedentary, no change (referent group), (2) decreased activity, (3) increased activity, and (4) active, no change. Over a 7-year period, the relative risk (95% CI) of death was as follows: 0.21 (0.10 to 0.44) for the active, no change group; 0.11 (0.03 to 0.46) for the increased activity group; and 0.49 (0.26 to 0.90) for the decreased activity group. The relative risk of reinfarction was as follows: 0.40 (0.24 to 0.66) for the active, no change group; 0.22 (0.09 to 0.50) for the increased activity group; and 0.93 (0.59 to 1.42) for the decreased activity group. CONCLUSIONS: These findings are consistent with a beneficial role of PA for Mexican American and non-Hispanic white women and men who survive a first MI and have practical implications for the management of MI survivors.

Frequency and effects of apolipoprotein E polymorphism in Mexican-American NIDDM subjects.

We typed 254 non-insulin-dependent diabetic (NIDDM) Mexican Americans living in Starr County, Texas, for the three common apolipoprotein E (apoE) alleles. Typing was performed via DNA amplification and Hha I restriction. The allele frequencies (epsilon 2 = 0.041, epsilon 3 = 0.860, epsilon 4 = 0.099) were in Hardy-Weinberg equilibrium (chi 2 = 0.60, df = 3) and did not differ from a random sample from the same population (chi 2 = 0.16, df = 2). Analysis of variance was used to test for mean differences in lipid, lipoprotein, and glucose levels among apoE types. Significant differences among types were detected for low-density lipoprotein cholesterol (LDL-chol; P = 0.042, R2 = 2.6) and beta-lipoprotein cholesterol (P = 0.019, R2 = 3.3) levels. Mean LDL-chol in E2/3 individuals was 2.69 mM, E3/3 was 3.26 mM, and E4/3 was 3.36 mM. Mean beta-lipoprotein cholesterol in E2/3 individuals was 3.05 mM, E3/3 was 3.64 mM, and E4/3 was 3.67 mM. Based on these results, we conclude that the effects of the apoE polymorphism on lipid profiles and glucose levels are the same in NIDDM subjects as in nondiabetic Mexican Americans and other populations. Other studies investigating the role of apoE polymorphism in diabetic subjects have found increased triglyceride levels in individuals possessing an epsilon 2-allele and an increased frequency of the epsilon 2-allele in hyperlipidemic diabetic subjects. We found no significant difference in mean triglyceride levels among genotypes. Possible reasons for this discrepancy are discussed, including DNA- versus protein-typing methods.

Signal peptide-length variation in human apolipoprotein B gene. Molecular characteristics and association with plasma glucose levels.

We studied the molecular characteristics of three naturally occurring variants in the human apolipoprotein B (apoB) signal peptide, their frequencies in non-insulin-dependent diabetic and random populations, and their association with several measures of lipid and carbohydrate metabolism. In a random sample of 197 French whites, there were two common alleles, 5'beta SP-24 and 5'beta SP-27, with frequencies of 0.35 and 0.65, respectively. In a random sample of 181 Mexican Americans, there was an additional allele, 5'beta SP-29, with a frequency of 0.03. DNA sequence analysis indicated that the signal peptide alleles consisted of the following: 5'beta SP-29 encoded 29 amino acids in the signal peptide containing two copies of the sequence CTG GCG CTG encoding Leu-Ala-Leu and a consecutive run of eight Leu-encoding codons; 5'beta SP-27 encoded 27 amino acids with a run of only six Leu codons; 5'beta SP-24 encoded 24 amino acids and contained a single copy of CTG GCG CTG and a run of six Leu codons. In the sample of French whites, average apoAI and glucose levels were significantly different among signal peptide genotypes. 5'beta SP-24/24 homozygotes had higher apoAI levels than the two other signal peptide genotypes (1.59 vs. 1.42 g/L, respectively). Heterozygous 5'beta SP-24/27 individuals had the highest glucose levels. In the random sample of Mexican Americans, average glucose levels were also significantly different among signal peptide genotypes. However, the rank order of average glucose levels was not the same between the two samples.(ABSTRACT TRUNCATED AT 250 WORDS)

Identification of microsatellite markers near the human ob gene and linkage studies in NIDDM-affected sib pairs.

Non-insulin-dependent diabetes mellitus (NIDDM) is a complex metabolic disorder with a significant genetic component. Obesity is a frequent complicating factor for NIDDM. In the mouse, a number of single gene defects that result in obesity have been described. Mutations in one of these genes, the ob gene, results in both obesity and NIDDM. Recently, the cloning of the murine ob gene and its human homologue has been reported (Nature 372:425-432, 1994). In the present study, the contribution of genetic variation at the human ob locus to NIDDM susceptibility was assessed by analyzing allele sharing in NIDDM-affected sib pairs (ASPs) for markers located near the human ob gene. Four yeast artificial chromosome clones containing the human ob gene were isolated. These clones colocalized the ob gene and two microsatellite markers, D7S514 and D7S635, to a region of 280 kb on the long arm of human chromosome 7. The microsatellite markers were typed in 346 Mexican-American NIDDM-ASPs derived from 176 families and an additional 110 ethnically and geographically matched controls. No evidence of linkage or association between either microsatellite marker and NIDDM was observed in this population. These results suggest genetic variation in the human ob gene does not play a major role in susceptibility to NIDDM in Mexican-Americans.

Isolation of a cDNA clone encoding a KATP channel-like protein expressed in insulin-secreting cells, localization of the human gene to chromosome band 21q22.1, and linkage studies with NIDDM.

The metabolism of glucose in insulin-secreting cells leads to closure of ATP-sensitive K+ channels (KATP), an event that initiates the insulin secretory process. Defects in insulin secretion are a common feature of non-insulin-dependent diabetes mellitus (NIDDM), and the beta-cell KATP that couples metabolism and membrane potential is a candidate for contributing to the development of this clinically and genetically heterogeneous disorder. We screened a hamster insulinoma cDNA library by low-stringency hybridization with a probe coding for the G-protein-coupled inwardly rectifying K+ channel GIRK1/KGA and isolated clones encoding a protein, KATP-2, whose sequence is 90% similar to that of the recently described KATP-1, an ATP-sensitive K+ channel expressed in heart and other tissues. RNA blotting showed that KATP mRNA was present in insulin-secreting cells and brain but not in heart. To assess the contribution of KATP-2 to the development of NIDDM, the human KATP-2 gene (symbol KCNJ7) was isolated and mapped to chromosome band 21q22.1 by fluorescence in situ hybridization. A simple tandem repeat DNA polymorphism, D21S1255, was identified in the region of the KATP-2 gene, and linkage studies between this marker and NIDDM were carried out in a group of Mexican-American sib pairs with NIDDM. There was no evidence for linkage between D21S1255 and NIDDM, indicating that KATP-2 is not a major susceptibility gene in this population.

Calpains play a role in insulin secretion and action.

Studies of the genetic basis of type 2 diabetes suggest that variation in the calpain-10 gene affects susceptibility to this common disorder, raising the possibility that calpain-sensitive pathways may play a role in regulating insulin secretion and/or action. Calpains are ubiquitously expressed cysteine proteases that are thought to regulate a variety of normal cellular functions. Here, we report that short-term (4-h) exposure to the cell-permeable calpain inhibitors calpain inhibitor II and E-64-d increases the insulin secretory response to glucose in mouse pancreatic islets. This dose-dependent effect is observed at glucose concentrations above 8 mmol/l. This effect was also seen with other calpain inhibitors with different mechanisms of action but not with cathepsin inhibitors or other protease inhibitors. Enhancement of insulin secretion with short-term exposure to calpain inhibitors is not mediated by increased responses in intracellular Ca2+ or increased glucose metabolism in islets but by accelerated exocytosis of insulin granules. In muscle strips and adipocytes, exposure to both calpain inhibitor II and E-64-d reduced insulin-mediated glucose transport. Incorporation of glucose into glycogen in muscle also was reduced. These results are consistent with a role for calpains in the regulation of insulin secretion and insulin action.

An approach for identifying simple sequence repeat DNA polymorphisms near cloned cDNAs and genes. Linkage studies of the islet amyloid polypeptide/amylin and liver glycogen synthase genes and NIDDM.

Genetic factors contribute to the development of NIDDM, and genes involved in regulating pancreatic beta-cell function and insulin's effects on glucose metabolism are good candidates for being NIDDM susceptibility loci. However, testing candidate genes for linkage to NIDDM depends on the identification of highly informative DNA polymorphisms in or near the candidate locus. Here we describe an approach for identifying highly polymorphic markers near candidate genes that utilizes the emerging physical map of the human genome. A sequence-tagged site from the candidate gene is used to screen the Centre d'Etude du Polymorphisme Humain megabase-insert yeast artificial chromosome library, which contains information on the physical localization of >3,000 genetically mapped simple sequence repeat DNA polymorphisms. Thus, identification of a yeast artificial chromosome containing the candidate locus will in many instances also identify a physically linked simple sequence repeat DNA polymorphism that can be used as a marker for the candidate gene in linkage studies. We have used this approach to identify a marker for the islet amyloid polypeptide gene on chromosome 12. The physical mapping of this gene to a yeast artificial chromosome showed that it was in the same yeast artificial chromosome as the gene encoding liver glycogen synthase, another possible NIDDM susceptibility gene. Affected sib pair studies using a simple sequence repeat DNA polymorphism physically linked to the islet amyloid polypeptide and liver glycogen synthase genes showed no evidence for linkage with NIDDM, indicating that they are not major genes contributing to NIDDM susceptibility.

Origins of U.S. Hispanics. Implications for diabetes.

The purpose of this article was to characterize the origins of the United States Hispanic population and discuss the implications of these origins in the context of diabetes risk. Particular attention was focused on the genetic origins of the three major U.S. Hispanic groups, i.e., Mexican Americans, Puerto Ricans, and Cubans. The U.S. Census figures provided basic demographic information. Genetic marker data for ancestral populations were taken from a review of the literature and compendia. Genetic marker data for the Puerto Rican and Cuban populations were extracted from the literature. Genetic markers determined on approximately 1000 randomly selected Mexican Americans from Starr County, Texas, were taken as representative of the Mexican-American population. The Hispanic population is the second largest and fastest growing minority in the U.S. Estimates of the Hispanic population in 1988 indicated some 19.4 million residents, of whom 62% were classified as Mexican, 13% as Puerto Rican, and the remaining 25% as Cubans and others. Various lines of evidence can be used to characterize the Hispanic population and its origins. These include ethnohistory, self-assessment of ancestry, surname distributions, speech and cultural characteristics, quantitative traits, and genetic structure. Genetic data were used to estimate the contribution of putative ancestral populations to the contemporary gene pool. For Mexican Americans, 31% of the contemporary gene pool is estimated to be Native American derived, whereas 61 and 8% are Spanish and African derived, respectively. In Puerto Rico, the percentage of contributions of Spanish, Native American, and African admixture to the population are 45, 18, and 37%, respectively. For Cuba, the parallel estimates are 62, 18, and 20%. The high frequency of Native American-derived genes in the contemporary Hispanic population predict a higher frequency of non-insulin-dependent diabetes mellitus (NIDDM) under the assumption that genes are important in NIDDM etiology. Our results are consistent with the finding of the significant role of genes in determining risk.

The Starr County Diabetes Education Study: development of the Spanish-language diabetes knowledge questionnaire.

OBJECTIVE: This study reports the psychometric properties of the 24-item version of the Diabetes Knowledge Questionnaire (DKQ). RESEARCH DESIGN AND METHODS: The original 60-item DKQ was administered to 502 adult Mexican-Americans with type 2 diabetes who are part of the Starr County Diabetes Education Study. The sample was composed of 252 participants and 250 support partners. The subjects were randomly assigned to the educational and social support intervention (n = 250) or to the wait-listed control group (n = 252). A shortened 24-item version of the DKQ was derived from the original instrument after data collection was completed. Reliability was assessed by means of Cronbach's coefficient alpha. To determine validity, differentiation between the experimental and control groups was conducted at baseline and after the educational portion of the intervention. RESULTS: The 24-item version of the DKQ (DKQ-24) attained a reliability coefficient of 0.78, indicating internal consistency, and showed sensitivity to the intervention, suggesting construct validation. CONCLUSIONS: The DKQ-24 is a reliable and valid measure of diabetes-related knowledge that is relatively easy to administer to either English or Spanish speakers.

Prevalence and determinants of type 2 diabetes among Filipino-Americans in the Houston, Texas metropolitan statistical area.

OBJECTIVE: The few available studies suggest that Filipino-Americans have an increased risk for developing type 2 diabetes. The purpose of this study was to determine the prevalence of previously diagnosed type 2 diabetes and its major risk factors among Filipino-Americans. RESEARCH DESIGN AND METHODS: A cross-sectional survey was conducted in the Houston, Texas, metropolitan statistical area between September 1998 and March 2000. The convenience sample included 831 Filipino-American participants aged 20-74 years. The major risk factors assessed were age, sex, family history of diabetes, socioeconomic status, obesity (BMI >30), physical inactivity, acculturation, region of birth and, in women, history of gestational diabetes and delivery of a baby weighing > 9 lb. RESULTS: Overall prevalence was estimated to be 16.1% (95% CI 13.5-18.7). Multivariate logistic regression analyses identified independent risk factors: increasing age from ages 35-44 years (odds ratio [OR] 5.6, 95% CI 1.5-20.5) to 65-74 years (34.2, 7.2-163.0); male sex (1.8, 1.1-32.1); family history of diabetes (4.7, 2.6-8.5); obesity (3.6, 1.4-9.0); region of birth, Mindanao (3.2, 1.3-7.7); and, among women, gestational diabetes (21.7, 6.7-69.7) and low income (5.3, 1.4-20.2). CONCLUSIONS: The study observed a high prevalence of type 2 diabetes and supports earlier studies suggesting that Filipinos are at higher risk for type 2 diabetes than the U.S. non-Hispanic white population.

Mortality of Mexican Americans with NIDDM. Retinopathy and other predictors in Starr County, Texas.

OBJECTIVE: To determine the rate and risk factors of mortality in a cohort of Mexican Americans with NIDDM. RESEARCH DESIGN AND METHODS: A cohort of 353 Mexican Americans with NIDDM were identified between 1981 and 1986. All individuals underwent extensive evaluations that included physical, historical, ophthalmological, and laboratory assessments. This cohort was followed prospectively for a mean of 8 yr. Follow-up included mortality surveillance, death certificate extraction, and a combination of annual and intermediate examinations. RESULTS: The cohort experienced 67 mortality events. One-third of all deaths were premature < 65 yr of age) and most often were attributed to diseases of the heart (60.0%). In no case was diabetes listed as the cause of death, although it was listed as a contributing cause in 25.5% of cases. Men had a higher mortality rate than women. In both sexes, baseline retinopathy was identified as an important predictor of subsequent mortality. Mortality was significantly elevated in those with nonproliferative retinopathy and even further elevated in those with proliferative disease (relative risks of > or = 4 for proliferative disease). CONCLUSIONS: Mexican Americans with NIDDM are experiencing premature and excessive mortality compared with the general population. The results clearly link microvascular complications with macrovascular disease, but this link is not explained by a more untoward profile of traditional cardiovascular risk factors. Retinopathy appears to serve as an important monitor of the progression of diabetes and when identified would warrant aggressive action to inhibit or slow the processes leading to subsequent mortality.

The GENNID Study. A resource for mapping the genes that cause NIDDM.

OBJECTIVE: To develop a resource, consisting of comprehensive data and lymphoblastoid cell lines, of well-characterized NIDDM families that will be available to the scientific community for genetic studies of NIDDM. RESEARCH DESIGN AND METHODS: Non-Hispanic white, Hispanic, African-American, and Japanese-American multiplex NIDDM families, with a minimum of one affected sib-pair, are being collected by the eight Harold Rifkin Family Acquisition Centers. Detailed family and medical histories are obtained from all participants. Family members with diabetes have fasting blood samples drawn, while nondiabetic family members have an oral glucose tolerance test and, when possible, insulin sensitivity and insulin secretion measurements by frequently sampled intravenous glucose tolerance testing or euglycemic insulin clamp. Lymphoblastoid cell lines are established for all participants. RESULTS: Over 1,400 individuals from approximately 220 families have been studied since the start of the GENNID (Genetics of NIDDM) program in July 1993. The goal is that by July 1997, data from 300 non-Hispanic white families, > 100 Hispanic families, > 100 African-American families, and 15 Japanese-American families will have been collected. CONCLUSIONS: The identification of the genes responsible for NIDDM may now be achievable, but only if sound phenotypic data are linked to genetic material from a large number of well-described multiplex families. The GENNID project of the American Diabetes Association is creating a comprehensive resource that will expedite the identification of the genetic basis of NIDDM.

Food-frequency questionnaire validation among Mexican-Americans: Starr County, Texas.

A food-frequency questionnaire (FFQ) for low-income Mexican-Americans in Starr County, Texas, was developed as part of an epidemiologic study of gallbladder disease during 1985 and 1986. The FFQ was developed from 7-day food records collected from the first sample. In the validity study, using the second sample, correlations between nutrients calculated from 3-day food records and the FFQ were 0.77, 0.76, and 0.61 for energy, total fat, and saturated fat, respectively. In the reliability study, using the third sample, for the 1-month interval between baseline and a repeat FFQ measurement correlations ranged from 0.90 for energy to 0.85 for total fat and for the 2-month interval they were 0.84 for energy and 0.70 for total fat. The high correlations are largely explained by the lack of diversity in the diets of Starr County individuals which facilitated the high agreement between the FFQ and the food records for estimates of energy, fats, and cholesterol.