Search PubMed⌕ Search

Biomedical subjects

R L Hanson

Publications and source records attributed to R L Hanson.

At least 91 records · Page 5Linked to original sources

Preventing non-insulin-dependent diabetes.

Many risk factors for non-insulin-dependent diabetes mellitus (NIDDM), such as obesity, physical inactivity, and high-fat diet, can potentially be modified. Furthermore, some of the metabolic abnormalities, such as insulin resistance and impaired glucose tolerance, that predict diabetes can be improved by behavior modification and drug treatment. Thus, at least to some extent, NIDDM may be preventable. Several small clinical trials have addressed the hypothesis that NIDDM can be prevented by dietary modification, physical activity, or drug treatment. Some studies suggest a preventive effect, but the conclusions are limited by considerations of sample size, randomization, or intensity of the interventions. Consequently, the hypothesis that NIDDM is preventable requires further testing.

Behavior Therapy↗

Incidence and determinants of elevated urinary albumin excretion in Pima Indians with NIDDM.

OBJECTIVE: To examine the incidence and determinants of elevated urinary albumin excretion in Pima Indians with non-insulin-dependent diabetes mellitus (NIDDM). RESEARCH DESIGN AND METHODS: The incidence of elevated urinary albumin excretion (> or = 30 mg albumin/g creatinine) and its relationship with baseline characteristics was determined in 456 Pima Indians > or = 15 years old with NIDDM who were followed for up to 11.6 years (median 4.7 years). RESULTS: Of these 456 subjects, 192 (42%; 58 men, 134 women) developed elevated urinary albumin excretion, 172 of whom (90%) were within the microalbuminuric range (30-299 mg/g). The incidence of elevated urinary albumin excretion was related to retinopathy, type, of diabetes treatment, longer duration of diabetes, lower body mass index, and higher values of mean arterial pressure, HbA1, and fasting and 2-h postload plasma glucose concentration at the baseline examination, but not to sex. A relationship with cholesterol was found in durations of diabetes of > or = 10 years. The cumulative incidence of elevated albumin excretion was 17% after 5 years of NIDDM. CONCLUSIONS: The incidence of elevated urinary albumin excretion in Pima Indians with NIDDM is at least as high as that reported previously in insulin-dependent diabetes mellitus, and its major determinants are the same as those shown previously to predict the development of more advanced renal disease in this population.

Adolescent↗

Comparison of body size measurements as predictors of NIDDM in Pima Indians.

OBJECTIVE--To determine and compare the abilities of various anthropometric measurements to predict the development of non-insulin-dependent diabetes mellitus (NIDDM) in Pima Indian men and women. RESEARCH DESIGN AND METHODS--A total of 290 male and 443 female Pima Indians were followed for up to 6 years for the development of NIDDM. A proportional hazards analysis was used to assess the ability of anthropometric measurements evaluated at baseline to predict NIDDM. Receiver operating characteristic (ROC) curves were used to compare individual variables in predicting NIDDM. RESULTS--In separate models controlled for age and sex, body mass index (BMI), waist circumference, thigh circumference, waist-to-thigh ratio (WTR), weight, and percentage body fat (PBF) estimated by bioelectric resistance each predicted NIDDM, which developed in 30 men and 52 women. The highest incidence rate ratios (IRRs; for 1 SD of a variable) were for WTR in men and for PBF in women, although the confidence interval (CI) for PBF was wide. In stepwise analyses, WTR was the most significant predictor in men (IRR for 1 SD = 1.58, 95% CI = 1.20-2.07), and BMI was the most significant predictor in women (IRR for 1 SD = 1.65, 95% CI = 1.29-2.11). However, by ROC analyses, thigh circumference was the only variable significantly worse than WTR in men or BMI in women at predicting NIDDM. CONCLUSIONS-- Measurements such as waist circumference, WTR, weight, and BMI may be useful as more complicated measurements, such as PBF by bioelectrical resistance, for identifying groups of individuals whose body habitus places them at high risk of developing NIDDM.

Adolescent↗

Segregation analysis of non-insulin-dependent diabetes mellitus in Pima Indians: evidence for a major-gene effect.

Non-insulin-dependent diabetes mellitus (NIDDM) has a high prevalence in Pima Indians. The disorder is familial, but the extent to which genetic factors are involved in its etiology is largely unknown. Segregation analysis was used to determine whether familial aggregation of NIDDM in this population could reflect the action of a single major gene. The analysis included 2,697 subjects from 653 nuclear families in which both parents and at least one offspring had been examined in the course of a longitudinal epidemiological study. The REGTL program of the SAGE package was used to fit models in which age at onset of NIDDM is transmitted from parent to offspring under the unified model for segregation analysis. Likelihood-ratio tests were used to test hypotheses related to genetic transmission. The hypothesis of no major effect was strongly rejected (P < .01), as was that of no transmission of the major effect (P < .01). Mendelian transmission was not rejected (P = .91). Similar results were obtained when covariates for obesity and birth cohort were added to the models and when a power transformation of age at onset was estimated. A strong effect of birth cohort with earlier age at onset in the later born cohorts was observed (P < .01). The findings are consistent with the hypothesis that a major gene influences the risk for NIDDM in Pima Indians by affecting age at onset. The expression of this gene may depend on environmental factors that have become more prevalent in recent-birth cohorts.

Adolescent↗

Site-specific enzymatic hydrolysis of taxanes at C-10 and C-13.

The production of large amounts of paclitaxel for use as an anticancer treatment has been a challenging problem because of the low concentration of the compound in yew trees and its occurrence as part of a mixture of other taxanes. Two novel enzymes were isolated to facilitate the production of 10-deacetylbaccatin III, a precursor used for semisynthesis of paclitaxel and analogs. A strain of Nocardioides albus (SC13911) was isolated from soil and found to produce an extracellular enzyme that specifically removed the C-13 side chain from paclitaxel, cephalomannine, 7-beta-xylosyltaxol, 7-beta-xylosyl-10-deacetyltaxol, and 10-deacetyltaxol. The enzyme was purified to near homogeneity to give a polypeptide with 47,000 M(r) on a sodium dodecyl sulfate gel. A strain of Nocardioides luteus (SC13912) isolated from soil was found to produce an intracellular 10-deacetylase that removed the 10-acetate from baccatin III and paclitaxel. The 10-deacetylase was purified to give a polypeptide with 40,000 M(r) on a sodium dodecyl sulfate gel. Treatment of extracts prepared from a variety of yew cultivars with the C-13-deacylase and C-10-deacetylase converted a complex mixture of taxanes primarily to 10-deacetylbaccatin III and increased the amount of this key precursor by 4-24 times.

Bridged Bicyclo Compounds↗

Familial and metabolic factors related to blood pressure in Pima Indian children.

High blood pressure, abnormal glucose tolerance, and obesity are frequently associated with each other, but the mechanism of these associations is poorly understood. Studying them in children may help in understanding the pathogenesis of hypertension. Blood pressure, height, weight, and plasma glucose and serum insulin concentrations during a 75-g oral glucose tolerance test were measured in 1,698 Pima Indian children aged 6-17 years who participated in an ongoing epidemiologic study. Weight relative to height was used as an index of obesity. The parents of many of the children were also examined. Fasting and 2-hour glucose and insulin concentrations, adjusted for age, sex, and relative weight, were positively related to systolic blood pressure but not to diastolic blood pressure. Relative weight, 2-hour glucose, and fasting insulin concentrations were independently and significantly associated with systolic blood pressure in a stepwise regression analysis that included age and sex. After parental hypertension was taken into account, maternal but not paternal non-insulin-dependent diabetes mellitus, controlled for the child's relative weight and glucose and insulin concentrations, was significantly associated with higher blood pressure in children. The stronger association with maternal diabetes suggests a greater sharing of environmental factors between mother and child than between father and child, but familial similarities in obesity and glucose and insulin concentrations, the diabetic intrauterine milieu, and shared environmental factors probably all contribute to this association.

Adolescent↗

Comparison of tests for glycated haemoglobin and fasting and two hour plasma glucose concentrations as diagnostic methods for diabetes.

OBJECTIVE: To compare the ability of tests measuring two hour plasma glucose, fasting plasma glucose, and glycated haemoglobin concentrations in predicting the specific microvascular complications of non-insulin dependent diabetes mellitus. DESIGN: Cross sectional and longitudinal analysis of the relation between complications and concomitant results of the three tests. SETTING: Gila River Indian Community, Arizona. SUBJECTS: Pima Indians (cross sectional, n = 960), aged 25 years or above who were not receiving insulin or oral hypoglycaemic treatment at the baseline examination. MAIN OUTCOME MEASURES: Development of retinopathy and nephropathy. RESULTS: Cross sectionally, frequency distributions of logarithms of the three sets of results were bimodal, with the prevalence of retinopathy and nephropathy being, respectively, 12.0-26.7 and 3.9-4.2 times as high above as below cut off points which minimised overlap (two hour plasma glucose concentration 12.6 mmol/l; fasting plasma glucose concentration 9.3 mmol/l; glycated haemoglobin (HbA1c) concentration 7.8%). Longitudinally, each of the three measures of glycaemia significantly predicted the development of retinopathy (P < 0.0001) and nephropathy (P < 0.05). Receiver operating characteristic curves showed that two hour plasma glucose concentration was superior to fasting plasma glucose concentration (P < 0.05) for prevalent cases of retinopathy, but otherwise no variable had a significant advantage for detecting incident or prevalent cases of either complication. CONCLUSIONS: These findings suggest that determination of glycated haemoglobin or fasting plasma glucose concentrations alone may be acceptable alternatives to measuring glucose concentration two hours after challenge with 75 g glucose for the diagnosis of diabetes.

Adult↗

Birth weight and non-insulin dependent diabetes: thrifty genotype, thrifty phenotype, or surviving small baby genotype?

OBJECTIVE: To determine the prevalence of diabetes in relation to birth weight in Pima Indians. DESIGN: Follow up study of infants born during 1940-72 who had undergone a glucose tolerance test at ages 20-39 years. SETTING: Gila River Indian community, Arizona. SUBJECTS: 1179 American Indians. MAIN OUTCOME MEASURE: Prevalence of non-insulin dependent diabetes mellitus (plasma glucose concentration > or = 11.1 mmol/l two hours after ingestion of carbohydrate). RESULTS: The prevalence was greatest in those with the lowest and highest birth weights. The age adjusted prevalences for birth weights < 2500 g, 2500-4499 g, and > or = 4500 g were 30%, 17%, and 32%, respectively. When age, sex, body mass index, maternal diabetes during pregnancy, and birth year were controlled for, subjects with birth weights < 2500 g had a higher rate than those with weights 2500-4499 g (odds ratio 3.81; 95% confidence interval 1.70 to 8.52). The risk for subsequent diabetes among higher birthweight infants (> or = 4500 g) was associated with maternal diabetes during pregnancy. Most diabetes, however, occurred in subjects with intermediate birth weights (2500-4500 g). CONCLUSIONS: The relation of the prevalence of diabetes to birth weight in the Pima Indians is U shaped and is related to parental diabetes. Low birth weight is associated with non-insulin dependent diabetes. Given the high mortality of low birthweight infants selective survival in infancy of those genetically predisposed to insulin resistance and diabetes provides an explanation for the observed relation between low birth weight and diabetes and the high prevalence of diabetes in many populations.

Adult↗

Crystallization and quaternary structure analysis of the NAD(+)-dependent leucine dehydrogenase from Bacillus sphaericus.

The NAD(+)-dependent leucine dehydrogenase from Bacillus sphaericus has been crystallized by the hanging drop method of vapour diffusion, using ammonium sulphate as the precipitant. The crystals belong to the tetragonal system and are in space group I4, with unit cell dimensions of a = b = 138.4 A and c = 121.8 A. Considerations of the values of Vm, the space group symmetry and an analysis of a self-rotation function calculated on a preliminary data set collected to 3 A resolution show that the asymmetric unit contains a dimer with the twofold axis perpendicular to the crystallographic four fold, indicating that the quaternary structure of this enzyme is octameric. Leucine dehydrogenase belongs to a superfamily of amino acid dehydrogenases which display considerable differences in amino acid specificity and elucidation of its three-dimensional structure should enable the molecular basis of this differential specificity to be examined in detail.

Amino Acid Oxidoreductases↗

Decreasing incidence and prevalence of rheumatoid arthritis in Pima Indians over a twenty-five-year period.

OBJECTIVE: To evaluate temporal trends in the incidence of rheumatoid arthritis (RA). METHODS: Incident cases of RA were identified among a population-based cohort of Pima Indians in Arizona over the period 1965-1990. RESULTS: Among 2,894 subjects, 78 incident cases of RA were identified. The age-adjusted incidence declined by 55% in men (Ptrend = 0.225), and by 57% in women (Ptrend = 0.017) after controlling for oral contraceptive or estrogen use and for pregnancy experience. During the same period, age-adjusted prevalence rates of active RA decreased by 29% in men (Ptrend = 0.63) and by 40% in women (Ptrend = 0.02). Fewer than 17% of subjects with known RA were taking slow-acting antirheumatic drugs (SAARDs) in 1990. CONCLUSION: The decrease in incidence and prevalence of RA in this population over such a short period implicates the involvement of an environmental factor(s), other than exogenous estrogens, in the pathogenesis of the disease. However, the possibility that the observed decrease might be explained by an increased use of SAARDs in subjects with RA cannot be excluded.

Adolescent↗

A cross-sectional and longitudinal comparison of the Rome criteria for active rheumatoid arthritis (equivalent to the American College of Rheumatology 1958 criteria) and the American College of Rheumatology 1987 criteria for rheumatoid arthritis.

OBJECTIVE: To compare the diagnostic properties of the Rome 1961 criteria for active rheumatoid arthritis (RA) and the American College of Rheumatology (ACR; formerly, the American Rheumatism Association) 1987 criteria for RA with regard to their ability to classify, diagnose, and predict outcome in RA. METHODS: Analysis of cross-sectional and longitudinal data from repeated health examinations and review of clinical records of 3,509 Pima Indians followed up from January 1966 to December 1990. RESULTS: The ACR 1987 criteria identified approximately 50% of the cases identified by the Rome 1961 criteria, in both cross-sectional and longitudinal analyses. The ACR 1987 criteria were better predictors of subsequent development of a clinically supported diagnosis and treatment with slow-acting antirheumatic drugs (both P < 0.001), but were less sensitive than the Rome 1961 criteria for detecting cases for which there already was a clinically supported diagnosis (P < 0.001). CONCLUSION: In a population-based analysis, the ACR 1987 criteria are less sensitive for detecting clinical disease, but predict a clinically more severe prognosis, compared with the Rome 1961 criteria. The sensitivity of both sets of criteria to identify clinical disease is improved if multiple examinations or inactive disease are taken into account.

Arizona↗

Glucose, insulin concentrations and obesity in childhood and adolescence as predictors of NIDDM.

Metabolic abnormalities antedate the development of non-insulin-dependent diabetes mellitus (NIDDM) by some years. How these metabolic abnormalities relate to the genetic component of the disease and to the subsequent prediction of diabetes is unknown. The present study was designed to examine the association of parental diabetes with relative weight, fasting and 2-h plasma glucose and fasting and 2-h serum insulin in childhood, and to identify which of these variables were most predictive of subsequent NIDDM. Subjects comprised 1258 Pima Indians aged 5-19 years with normal glucose tolerance participating in a longitudinal population-based study. Age-sex-adjusted values of relative weight, fasting and 2-h glucose and fasting and 2-h insulin were positively associated with parental diabetes. Only one of 138 subjects with two non-diabetic parents developed diabetes. Among 1120 subjects with at least one diabetic parent, 101 (9.0%) developed diabetes during a mean follow up of 8.4 years. Fasting insulin was a significant predictor of diabetes, but did not add to the predictive value of relative weight. Relative weight and 2-h and fasting plasma glucose were the variables most predictive of NIDDM in childhood and adolescence. Against a background of parental diabetes, high fasting insulin concentrations predict diabetes, compatible with the hypothesis that insulin resistance is an early metabolic abnormality leading to NIDDM. In this study, however, its predictive power did not add significantly to that of relative weight, with which it was correlated.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Gravidity, obesity, and non-insulin-dependent diabetes among Pima Indian women.

PURPOSE: To evaluate the relationships among gravidity, obesity, and non-insulin-dependent diabetes mellitus in Pima Indian women. SUBJECTS AND METHODS: Pima Indian women (n = 2,779) participating in a longitudinal epidemiologic study of diabetes were evaluated in both cross-sectional and longitudinal analyses. RESULTS: The prevalence of non-insulin-dependent diabetes was higher among women who had never been pregnant than among those who had been pregnant (age- and obesity-adjusted odds ratio = 2.0; 95% confidence interval = 1.5 to 2.7). Controlled for age and obesity, nondiabetic women who had never been pregnant had significantly higher fasting plasma glucose concentrations by 2% (P = 0.004), higher fasting serum insulin concentrations by 8% (P = 0.09), and higher 2-hour serum insulin concentrations by 10% (P = 0.07) than nondiabetic women who had been pregnant. Among 1,025 women observed for an average of 8 years, those who had not been pregnant by the baseline examination were at significantly higher risk for developing non-insulin-dependent diabetes before the age of 40 years (incidence rate ratio = 1.5; 95% confidence interval = 1.2 to 2.1), but that difference could be accounted for by a higher degree of obesity. CONCLUSIONS: We hypothesize that Pima Indian women who have a high risk for non-insulin-dependent diabetes develop obesity and hyperinsulinemia at an early age, and that may be responsible for decreased fertility because of associated changes in sex hormones.

Adult↗

Comparison of World Health Organization and National Diabetes Data Group procedures to detect abnormalities of glucose tolerance during pregnancy.

OBJECTIVE: To compare the one-step procedure proposed by the World Health Organization (WHO) with the two-step procedure proposed by the National Diabetes Data Group (NDDG) for the identification of abnormalities of glucose tolerance during pregnancy. RESEARCH DESIGN AND METHODS: One hundred twenty-seven non-diabetic Pima Indian women had a 75-g 2-h glucose tolerance test (WHO criteria). Those with an elevated 1-h glucose concentration (> or = 7.8 mmol/l) were referred for a 100-g 3-h glucose tolerance test (National Diabetes Data Group criteria). The effectiveness of the two test procedures was determined by comparing the frequency of macrosomia and cesarean section as outcomes of pregnancy. RESULTS: Of 42 women with 1-h plasma glucose concentrations > or = 7.8 mmol/l, 13 had no 100-g test, 27 had a normal test, and 2 had an abnormal test. Both women (100%) with abnormal two-step 100-g tests also had abnormal one-step 75-g tests, but only 2 of the 11 women (18%) with an abnormal one-step test had an abnormal two-step test. Sixteen of the 127 women delivered babies weighing > or = 4,000 g. Six of these women (38%) were correctly identified as abnormal using the one-step test and one (6%) using the two-step test. Of seven women delivering by cesarean section, four (57%) had abnormal one-step tests, but none had an abnormal two-step test. CONCLUSIONS: The one-step WHO test for glucose tolerance during pregnancy was abnormal in a greater percentage of women with adverse outcomes than the more cumbersome two-step NDDG test. The one-step test has the added advantage of being directly comparable to the standard glucose tolerance test used in nonpregnant women.

Arizona↗

Comparison of screening tests for non-insulin-dependent diabetes mellitus.

BACKGROUND: Screening for non-insulin-dependent diabetes mellitus (NIDDM) can be useful in clinical practice and in epidemiologic and genetic studies, but the available information for choosing between screening methods is limited. In this study, characteristics of several screening tests for NIDDM were compared. METHODS: Among Pima Indians participating in an epidemiologic study, the sensitivity and specificity for detecting NIDDM of fasting plasma glucose (FPG) levels and two measures of glycated hemoglobin (HbA1 or HbA1c) were compared in 2092 fasting subjects. Glycated hemoglobin, quantitative glycosuria, and dipstick glycosuria were compared in 237 nonfasting subjects. Diabetes was diagnosed using an oral glucose tolerance test if the 2-hour postload venous plasma glucose concentration was 11.1 mmol/L (200 mg/dL) or greater. The area under the relative operating characteristic curve was used to compare tests. RESULTS: In fasting subjects, the sensitivity for detecting diabetes with 98% specificity was 78.8% for HbA1 level of 7.5% or greater, 80.3% for HbA1c level of 6.3% or greater, and 88.0% for FPG level of 6.83 mmol/L (123 mg/dL) or greater. By relative operating characteristic analysis, there were no significant differences between FPG and HbA1c, but FPG was significantly more sensitive than HbA1. In nonfasting subjects the sensitivity at 98% specificity was 92.9% for HbA1 level of 7.3% or greater, 80.6% for quantitative urine glucose level of 1.94 mmol/L (35 mg/dL) or greater, and 64.3% for trace or greater of dipstick glycosuria. The area under the relative operating characteristic curve was significantly greater for glycated hemoglobin than for either measure of glycosuria. CONCLUSIONS: Although FPG has the best screening properties, HbA1c, HbA1, and quantitative urine glucose also provide high specificity and approximately 80% sensitivity in detecting NIDDM. The choice of a particular method could depend on cost, convenience, and availability.

Adult↗

Rheumatoid arthritis and mortality. A longitudinal study in Pima Indians.

OBJECTIVE: To determine the effect of rheumatoid arthritis (RA) on mortality rates. METHODS: Longitudinal analyses of data from a cohort of Pima Indians from the Gila River Indian Community in Arizona, who were followed up during the period February 1965 through December 1989. RESULTS: Among 2,979 study subjects aged > or = 25 years, there were 858 deaths, 79 of which occurred in subjects with RA (36 men, 43 women). Age- and sex-adjusted mortality rates were slightly higher in subjects with RA than in those without (mortality rate ratio 1.28, 95% confidence interval [95% CI] 1.01-1.62). Among those with RA, mortality rates were higher in older subjects (mortality rate ratio 1.51 per 10-year increase in age, 95% CI 1.22-1.88), in male subjects (mortality rate ratio 2.23, 95% CI 1.44-3.45, adjusted for age), and in subjects with proteinuria (mortality rate ratio 1.88, 95% CI 1.02-3.46, adjusted for age and sex). Mortality rate ratios for these risk factors were similar in subjects without RA. In addition, among subjects with RA, rheumatoid factor (RF) positivity was predictive of death (mortality rate ratio 1.94, 95% CI 1.10-3.43), and the excess mortality was found primarily among subjects who were seropositive. The death rate from cardiovascular disease (mortality rate ratio 1.77, 95% CI 1.10-2.84) and from liver cirrhosis or other alcohol-related disease (mortality rate ratio 2.52, 95% CI 1.06-6.01) was increased in persons with RA. CONCLUSION: The results of this population-based study suggest that although the risk of mortality in subjects with RA is significantly higher than in those without RA, the risk ratio is in the lower range of that described previously in studies of clinic-based cohorts. RF positivity as a predictor of early death among subjects with RA indicates that the immunologic processes in seropositive RA may contribute to the events that eventually lead to early death.

Adult↗

Glycated haemoglobin, plasma glucose and diabetic retinopathy: cross-sectional and prospective analyses.

Among Pima Indians with Type 2 (non-insulin-dependent) diabetes mellitus the relationships between glycated haemoglobin (HbA1), fasting or 2-h post-load plasma glucose and diabetic retinopathy were examined by cross-sectional and prospective analyses, and the strengths of the associations were directly compared by receiver operating characteristic analysis. In the cross-sectional analysis, HbA1, fasting and 2-h plasma glucose were each significantly related to retinopathy among 789 diabetic subjects by separate logistic models. In a stepwise multiple logistic model in which HbA1, fasting and 2-h plasma glucose were included, HbA1 was selected as having the strongest association with retinopathy and neither fasting nor 2-h plasma glucose contributed significantly to the model once HbA1 was entered. Similarly, in the prospective analysis, HbA1, fasting and 2-h plasma glucose all predicted retinopathy in 227 diabetic subjects by separate proportional-hazards models. In a stepwise proportional-hazards model with HbA1, fasting and 2-h plasma glucose available to the model, HbA1 was again selected as having the strongest association with the incidence of retinopathy, and neither fasting nor 2-h plasma glucose significantly added to the prediction of retinopathy. A receiver operating characteristic analysis was used to determine if HbA1 was statistically significantly better than fasting or 2-h plasma glucose in assessing the risk for retinopathy. In neither the cross-sectional nor the prospective data did the area under the receiver operating characteristic curve for HbA1 differ significantly from that for fasting or 2-h plasma glucose (p > 0.05 for each).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗