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Biomedical subjects

W C Knowler

Publications and source records attributed to W C Knowler.

At least 127 records · Page 7Linked to original sources
PubMed1994

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↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1994

Prevention of non-insulin-dependent diabetes mellitus.

Non-insulin-dependent diabetes mellitus (NIDDM) is a chronic disease which may take several years to develop, presumably starting in most cases with genetic susceptibility. Development of NIDDM is influenced by obesity and physical inactivity. As these risk factors can be altered by behavioral modification, and some of the physiologic abnormalities predicting diabetes, such as insulin resistance and impaired glucose tolerance, can be improved by behavioral modification and with drugs, NIDDM is potentially preventable. This potential needs to be demonstrated by randomized clinical trials.

Diabetes Mellitus, Type 2↗
PubMed1994

Glycated haemoglobin predicts progression to diabetes mellitus in Pima Indians with impaired glucose tolerance.

Glycated haemoglobin could offer several practical advantages over the OGTT for assessing glucose metabolism. Initial cross-sectional studies (1983-1985) on 381 subjects (mostly Pima Indians) described the relationship between HbA1c (a specific glycated Hb) and the OGTT. We performed follow-up OGTTs and HbA1c measurements on 257 of these same subjects 1.6-6.1 years later. Subjects were again grouped according to both the result of the OGTT (normal, IGT or diabetes, by WHO criteria) and HbA1c result (normal or elevated based on mean +/- 1.96 SD of normal). Of 66 subjects with IGT at baseline, 47 (71%) had normal HbA1c and 19 (29%) had elevated HbA1c. Twenty-six (39%) of these subjects had diabetes at follow-up. Of these subjects with IGT, a significantly greater percentage of subjects with elevated HbA1c at baseline (68%) showed worsening to diabetes than those with a normal HbA1c (28%); (chi-square = 7.8, df = 1, p < 0.01). Thus, in subjects with IGT, glycated Hb may be a useful predictor of progression to diabetes.

Adolescent↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1994

Hyperinsulinemia is associated with menstrual irregularity and altered serum androgens in Pima Indian women.

To determine whether hyperinsulinemia is associated with menstrual irregularity or hyperandrogenemia among Pima Indians, a population with a high prevalence of hyperinsulinemia, we retrospectively studied 20 hyperinsulinemic (higher insulin [HI ) and 20 relatively nonhyperinsulinemic (lower insulin [LI]) nondiabetic Pima women 18 to 45 years of age. Reproductive histories were obtained by review of medical records. Stored serum samples were used for measurement of total testosterone, androstenedione, and dehydroepiandrosterone sulfate (DHEAS) levels. Fifty percent (nine of 18) of HI women had irregular menses, as compared with none of the LI women (0 of 19, P = .0004). HI women were significantly more obese than LI women. Serum testosterone and androstenedione levels were similar in HI and LI women (median testosterone, 1.13 v 1.13 nmol/L, P = .55; median androstenedione, 3.79 v 3.26 nmol/L, P = .90). Serum DHEAS was lower in HI than in LI women (median, 2.85 v 4.55 mumol/L, P < .01). HI women with irregular menses had significantly higher testosterone levels than HI women with regular menses (median, 1.62 v 0.76, nmol/L, P = .04). Androstenedione and DHEAS levels were not different between these women. In conclusion, the association of obesity, hyperinsulinemia, irregular menstruation, and high testosterone concentration described in the polycystic ovarian syndrome (PCO) also occurs in Pima Indian women. Moreover, low concentrations of DHEAS are associated with hyperinsulinemia in these women.

Adolescent↗
PubMed1994

Linkage analysis of acute insulin secretion with GLUT2 and glucokinase in Pima Indians and the identification of a missense mutation in GLUT2.

The acute insulin response (AIR), a measure of pancreatic beta-cell function, aggregates in families and is a predictor for the development of non-insulin-dependent diabetes mellitus (NIDDM) in insulin-resistant Pima Indians. To assess the genetic components of AIR and NIDDM, polymorphic dinucleotide repeat regions in two candidate genes, the liver/islet glucose transporter gene (GLUT2) and the glucokinase gene, were evaluated. Sib-pair linkage analyses were performed to determine if linkage exists between these marker loci and measurements of AIR and NIDDM. No linkage was found between glucokinase and either AIR or NIDDM. Robust sib-pair linkage analyses suggest linkage between GLUT2 and acute insulin response (P = 0.04), but no linkage was observed with NIDDM. The coding region of the GLUT2 gene was screened for mutations using polymerase chain reaction-single-strand conformation polymorphism analysis. A single base change was identified in exon 3 in approximately 5% of the study population, and it constitutes the first reported mutation in the human GLUT2 gene. This base change resulted in an amino acid substitution (Thr110-->Ile110) in the second membrane-spanning region of the GLUT2 protein. No significant association was noted between AIR and the presence or absence of the mutation. Thus, this mutation in GLUT2 is unlikely the cause of a low AIR in Pima Indians.

Amino Acid Sequence↗
PubMed1994

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↗
PubMed1994

Obesity in Pima Indians: genetic segregation analyses of body mass index complicated by temporal increases in obesity.

During the past half-century the prevalence of obesity in developed countries has increased greatly. Such short-term changes in prevalence must be environmentally determined, but genes can mediate response to environmental change, for example, through variable gene penetrance and expression. Obesity differences between bith cohorts complicate the interpretation of phenotypic comparisons between generations that span periods of change. Genetic segregation analyses of the body mass index in 618 Pima Indian nuclear families (2 generations) identified recessive major gene inheritance, which is the same pattern of transmission that has been found in several other populations. However, within-birth-cohort analyses of siblings (one generation) uniformly supported codominant major gene inheritance with no polygenic heritability. For untransformed data transmission probabilities were Mendelian in the later-born cohort and in the combined sample of siblings. After transformation to remove skewness, transmission probabilities were Mendelian only in the earlier-born cohort (i.e., those siblings born before a period of marked temporal increase following World War II). A higher penetrance of codominant obesity susceptibility genes in the younger generation would result in some genetically obese individuals who have no affected parents, thus simulating recessive inheritance. Taken together, the results of these analyses suggest that the recessive pattern we identified in the Pima Indian nuclear families could be accounted for by temporal changes in penetrance of codominant obesity-predisposing genes. By implication, more modest temporal increases in white and black populations could in part account for the recessive pattern of inheritance described by several investigators.

Adolescent↗
PubMed1993

Insulin resistance and insulin secretory dysfunction as precursors of non-insulin-dependent diabetes mellitus. Prospective studies of Pima Indians.

BACKGROUND: The relative roles of obesity, insulin resistance, insulin secretory dysfunction, and excess hepatic glucose production in the development of non-insulin-dependent diabetes mellitus (NIDDM) are controversial. We conducted a prospective study to determine which of these factors predicted the development of the disease in a group of Pima Indians. METHODS: A body-composition assessment, oral and intravenous glucose-tolerance tests, and a hyperinsulinemic--euglycemic clamp study were performed in 200 non-diabetic Pima Indians (87 women and 113 men; mean [+/- SD] age, 26 +/- 6 years). The subjects were followed yearly thereafter for an average of 5.3 years. RESULTS: Diabetes developed in 38 subjects during follow-up. Obesity, insulin resistance (independent of obesity), and low acute plasma insulin response to intravenous glucose (with the degree of obesity and insulin resistance taken into account) were predictors of NIDDM: The six-year cumulative incidence of NIDDM was 39 percent in persons with values below the median for both insulin action and acute insulin response, 27 percent in those with values below the median for insulin action but above that for acute insulin response, 13 percent in those with values above the median for insulin action and below that for acute insulin response, and 0 in those with values originally above the median for both characteristics. CONCLUSIONS: Insulin resistance is a major risk factor for the development of NIDDM: A low acute insulin response to glucose is an additional but weaker risk factor.

Adult↗
PubMed1993

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↗
PubMed1993

Increased mortality with gallstone disease: results of a 20-year population-based survey in Pima Indians.

OBJECTIVE: To determine if gallstone disease is associated with an increased risk for malignancy and higher total mortality in Pima Indians. DESIGN: Inception cohort. SETTING: American Indian community. PARTICIPANTS: Age- and sex-stratified random population-based sample. MEASUREMENTS: Between 1966 and 1969, an age- and sex-stratified random sample of Pima Indians from the Gila River Indian Community in Arizona was examined to identify evidence of gallstone disease defined as either gallstones (oral cholecystography) or previous cholecystectomy. During 20 years of follow-up, deaths were recorded and underlying causes of death, according to death certificates, were determined. RESULTS: Among 383 persons with known gallbladder status, 186 (49%) died: 133 among the 222 persons with gallstone disease and 53 among the 161 without. The overall death rate was higher in persons with gallstone disease than in those with normal gallbladders. The age- and sex-adjusted death rate ratio was 1.9 (95% Cl, 1.3 to 2.7). Furthermore, the death rate attributed to malignancies was 6.6 times (Cl, 1.3 to 33.1) as high in persons with gallstone disease as in those with normal gallbladders. Of the 20 fatal malignancies in persons with gallstone disease, 11 occurred in the digestive tract, of which six involved the gallbladder or bile ducts. CONCLUSIONS: Increased cancer mortality and total mortality were found in Pima Indians with gallstone disease. Although plausible explanations exist for the increased cancer mortality, the increased death rates due to other causes are unexplained. Whether cholecystectomy would change this risk is unknown.

Adolescent↗
PubMed1993

Obesity in Pima Indians: large increases among post-World War II birth cohorts.

Several studies have shown secular increases in obesity during the past 35 years, and others have reported increases in dietary fat consumption during the same period. Here we report a dramatic increase in obesity among Pima Indians born after World War II that appears to be associated with increased exposure to Western customs and diet following 1945. We examined the body mass index (BMI = weight in kilograms/height2 in meters) of 1,128 male and 1,372 female Pima Indians aged 15-65 years who were born between 1901 and 1964 and were examined between 1965 and 1990. We found large increases in BMI among Pima Indian men and women in post-World War II birth cohorts (1945 and later). The parallel changes in body mass index, dietary fat, and exposure to Western culture following World War II suggest that culturally mediated changes in diet and level of physical activity associated with modern industrialized society may have led to the large increases in obesity in the Pima Indians and to smaller parallel changes observed worldwide in westernized countries.

Acculturation↗