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Biomedical subjects

W C Knowler

Publications and source records attributed to W C Knowler.

At least 145 records · Page 8Linked to original sources
PubMed1993

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↗
PubMed1993

The association of physical activity with obesity, fat distribution and glucose intolerance in Pima Indians.

The relationships between physical activity, obesity, fat distribution and glucose tolerance were examined in the Pima Indians who have the highest documented incidence of non-insulin-dependent diabetes. Fasting and 2-h post-load plasma glucose concentrations, body mass index, and waist-to-thigh circumference ratios were determined in 1054 subjects aged 15-59 years. Current (during the most recent calendar year) and historical (over a lifetime) leisure and occupational physical activity were determined by questionnaire. Current physical activity was inversely correlated with fasting and 2-h plasma glucose concentrations, body mass index and waist-to-thigh ratios for most sex-age groups even when diabetic subjects were excluded. Controlled for age, obesity and fat distribution, activity remained significantly associated with 2-h plasma glucose concentrations in males. In subjects aged 37-59 years, individuals with diabetes compared to those without reported significantly less leisure physical activity during the teenage years (median hours per week of activity, 9.1 vs 13.2 for men; 1.0 vs 2.2 for women). Controlled for body mass index, sex, age and waist-to-thigh ratio, subjects who reported low levels of historical leisure physical activity had a higher rate of diabetes than those who were more active. In conclusion, current physical activity was inversely related to glucose intolerance, obesity and central distribution of fat, particularly in males. Subjects with diabetes were currently less active and reported less historical physical activity than non-diabetic subjects. These findings suggest that activity may protect against the development of non-insulin-dependent diabetes both directly and through an influence on obesity and fat distribution.

Adipose Tissue↗
PubMed1993

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↗
PubMed1993

Pre-diabetic blood pressure predicts urinary albumin excretion after the onset of type 2 (non-insulin-dependent) diabetes mellitus in Pima Indians.

Blood pressure was measured in 490 non-proteinuric Pima Indians from the Gila River Indian Community in Arizona at least 1 year before the diagnosis of Type 2 (non-insulin-dependent) diabetes mellitus. Urine albumin concentration was measured in the same subjects 0-24 years (mean 5 years) after diabetes was diagnosed. Prevalence rates of abnormal albumin excretion (albumin-to-creatinine ratio > or = 100 mg/g) after the onset of Type 2 diabetes were 9%, 16%, and 23%, respectively, for the lowest to highest tertiles of pre-diabetic mean blood pressure. When controlled for age, sex, duration of diabetes and pre-diabetic 2-h post-load plasma glucose concentration, higher pre-diabetic mean blood pressure predicted abnormal urinary excretion of albumin after the onset of diabetes. This finding suggests that the higher blood pressure seen in diabetic nephropathy is not entirely a result of the renal disease, but may precede and contribute to it.

Adolescent↗
PubMed1993

Determinants of end-stage renal disease in Pima Indians with type 2 (non-insulin-dependent) diabetes mellitus and proteinuria.

To identify factors related to the development of end-stage renal disease after the onset of proteinuria, its incidence was determined in 364 Pima Indians aged 35 years or older with Type 2 (non-insulin-dependent) diabetes mellitus and proteinuria (protein-to-creatinine ratio > or = 0.5 g/g). Of these 364 subjects, 95 (36 men, 59 women) developed end-stage renal disease. The cumulative incidence was 40% 10 years after and 61% 15 years after the onset of proteinuria. The incidence of end-stage renal disease was significantly related to the duration of diabetes, the duration of proteinuria, higher 2-h plasma glucose concentration, type of diabetes treatment, and the presence of retinopathy at the time of recognition of the proteinuria, but not to age, sex, or blood pressure. Duration of proteinuria influenced the risk of end-stage renal disease, contingent, however, upon the duration of diabetes at the onset of proteinuria. The higher cumulative incidence of end-stage renal disease 15 years after the onset of proteinuria in Pima Indians (61%) than in Caucasians from Rochester, Minnesota (17%) may be attributable, in part, to the younger age of onset of Type 2 diabetes in Pima Indians than in Caucasians, to ethnic differences in susceptibility to renal disease, or to lower death rates among the Pima Indians from competing causes of death, such as coronary heart disease.

Adult↗
PubMed1993

Linkage of chromosomal markers on 4q with a putative gene determining maximal insulin action in Pima Indians.

Insulin action in vivo varies widely in nondiabetic Pima Indians. Not all of this variance is attributable to individual differences in obesity, physical fitness, sex, or age, and after correcting for these co-variates, measures of insulin action aggregate in families. Insulin action at maximally stimulating insulin concentrations has a trimodal frequency distribution, particularly among obese individuals. This is consistent with the hypothesis that a codominantly inherited autosomal gene, unrelated to obesity, determines MaxM in the population. Preliminary sib-pair linkage analyses indicated the possibility of linkage between MaxM and the GYPA/B locus (encoding the MNSs red cell surface antigens) on chromosome 4q. To confirm and extend these findings, 10 additional loci on 4q were typed in 123 siblings and many of their parents from 46 nuclear families. The results indicate significant (P < 0.001) linkage of the FABP2 and ANX5 loci on 4q with MaxM, and of FABP2 with fasting insulin concentration. No linkage was found between the 4q markers and obesity. Our findings indicate that a gene on 4q, near the FABP2 and ANX5 loci, contributes to in vivo insulin action in Pima Indians.

Adult↗
PubMed1993

Determinants of diabetes mellitus in the Pima Indians.

OBJECTIVE: To review the research findings on the determinants of diabetes mellitus in Pima Indians. RESEARCH DESIGN AND METHODS: Pima Indians in Arizona have participated in a longitudinal diabetes study that has provided data on and hypotheses about the development of NIDDM. Findings from this study are reviewed and updated. RESULTS: Frequency distributions of plasma glucose and HbA1 are bimodal in Pima adults, and substantial risk of the specific vascular complications of diabetes is confined to those in the higher components of these distributions. These findings contributed to the adoption of internationally recognized criteria for classification of glucose tolerance. Diabetes in the Pimas is strongly familial, and probably of genetic origin, although the precise nature of the gene or genes involved remains unknown. Obesity, which is at least in part environmentally determined, is a major factor interacting with the presumed genetic susceptibility to result in diabetes. The incidence of diabetes in the Pimas has increased during the last several decades, providing further evidence for environmental-genetic interaction. Longitudinal studies suggest that the progression from normal to diabetes can be considered to involve two stages. The first, primarily attributable to insulin resistance, leads to impaired glucose tolerance, and the second, which depends on insulin secretory failure, leads to worsening hyperglycemia and overt diabetes. CONCLUSIONS: The Pimas and many other American Indian populations suffer from a high incidence of diabetes and its characteristic disabling or fatal complications, and would benefit from continued research on the pathogenesis and prevention of the disease.

Adolescent↗
PubMed1993

Diabetes and obesity in the offspring of Pima Indian women with diabetes during pregnancy.

OBJECTIVE: To review the long-term effects of the diabetic pregnancy on the offspring among the Pima Indians of Arizona. RESEARCH DESIGN AND METHODS: Studies published by the Phoenix Epidemiology and Clinical Research branch of the National Institute of Diabetes and Digestive and Kidney Diseases, since the inception of the longitudinal diabetes studies in 1965 were reviewed. In addition, pertinent studies from other centers, mentioned as references in these publications, were reviewed. As far as possible, all original articles and abstracts on this aspect of the Pima Indian studies were discussed. RESULTS: The offspring of women who had diabetes during pregnancy, on average, were more obese and had higher glucose concentrations and more diabetes than the offspring of women who developed diabetes after pregnancy or who remained nondiabetic. Although no new analyses were attempted, several of the older publications were updated by repeating the analyses on later, expanded data sets. CONCLUSIONS: The diabetic pregnancy, in addition to its effects on the newborn, has effects on the subsequent growth and glucose metabolism of the offspring. These effects are in addition to genetically determined traits.

Adolescent↗
PubMed1993

Diabetic kidney disease in Pima Indians.

OBJECTIVE--To describe the natural history of kidney disease in Pima Indians with NIDDM. RESEARCH DESIGN AND METHODS--Review of previous studies describing diabetic kidney disease in this Native-American population and in other populations. RESULTS--NIDDM is the leading cause of renal failure in Pima Indians, among whom the incidence of ESRD is 23 times that of the general U.S. population. The high incidence of NIDDM and its early onset in the Pima undoubtedly contribute to this difference. The incidence of overt nephropathy and ESRD, as a function of diabetes duration, is at least as high in Pima Indians with NIDDM as that reported in other populations with IDDM. Furthermore, nearly all of the excess mortality associated with NIDDM is found in individuals with overt nephropathy. Mild elevations of UAE, which may be present even shortly after the onset of diabetes, predict the development of overt nephropathy in diabetic Pimas. Additional predictors include high blood pressure, level of glycemia, duration of diabetes, family history of diabetic nephropathy, and type of diabetes treatment. CONCLUSIONS--Diabetic kidney disease is a major cause of morbidity and mortality in Pima Indians. The natural history of diabetic kidney disease in this population is similar, in many ways, to the natural history described in individuals with IDDM.

Diabetes Mellitus, Type 1↗
PubMed1993

Development of impaired glucose tolerance with or without weight gain.

OBJECTIVE: To evaluate whether risk factors and changes in insulin concentrations differ in subjects who develop impaired glucose tolerance with or without weight gain. Hyperinsulinemia is a risk factor for impaired glucose tolerance, and insulin concentrations increase further with the development of impaired glucose tolerance. Its development, however, often is accompanied by weight gain, which, by itself, is associated with high insulin concentrations. RESEARCH DESIGN AND METHODS: Participants for this study were adult Pima Indians involved in an ongoing epidemiological study. Initially, all had normal glucose tolerance. During follow-up, 80 of 387 who did not gain weight developed impaired glucose tolerance, as did 295 of 1026 who gained weight. Risk factors for impaired glucose tolerance and the relationships between changes in weight and glucose and changes in insulin were evaluated by multivariate analyses. RESULTS: High baseline fasting insulin predicted impaired glucose tolerance regardless of weight after adjustment for age, sex, body mass index, and glucose. The development of impaired glucose tolerance was accompanied by a further increase in fasting and 2-h insulin, whether or not subjects gained weight. In both weight-change groups, impaired glucose tolerance was associated with more centralized fat distribution. CONCLUSIONS: Fasting hyperinsulinemia, a reflection of insulin resistance, is associated with the risk of developing impaired glucose tolerance whether or not weight is gained. Impaired glucose tolerance occurs when insulin resistance increases further. Weight gain is the most common precipitating factor. Aging and physical inactivity are other possible precipitating factors.

Adult↗
PubMed1993

Insulinemia in children at low and high risk of NIDDM.

OBJECTIVE: Fasting hyperinsulinemia in the presence of normoglycemia usually indicates insulin resistance and is characteristic of populations at high risk for developing NIDDM. Hyperinsulinemia predicts the development of impaired glucose tolerance and NIDDM in Pima Indians, a population with a high incidence of NIDDM. Insulin concentrations in population-based samples of children who have different risks of developing NIDDM later in life have not been reported previously. RESEARCH DESIGN AND METHODS: We compared fasting insulin concentrations in two populations of nondiabetic children, 6-19 yr of age: Pima Indians from southern Arizona and Caucasians from Minnesota. RESULTS: Insulin concentration varied with age, sex, glucose concentration, and relative weight. Mean fasting insulin concentration was 140.3 pM in Pima Indian males, 94.4 pM in Caucasian males, 171.5 pM in Pima Indian females, and 107.1 pM in Caucasian females. For each sex, the mean fasting insulin concentration, controlled for age, glucose, and relative weight, was significantly higher in the Pima Indians than in the Caucasians (P < 0.001). CONCLUSIONS: From a young age, Pima Indian children have higher fasting insulin concentrations than Caucasian children. As hyperinsulinemia predicts subsequent NIDDM, these data suggest that the susceptibility to NIDDM is manifest at a young age as fasting hyperinsulinemia.

Adolescent↗
PubMed1992

Native American mitochondrial DNA analysis indicates that the Amerind and the Nadene populations were founded by two independent migrations.

Mitochondrial DNAs (mtDNAs) from 167 American Indians including 87 Amerind-speakers (Amerinds) and 80 Nadene-speakers (Nadene) were surveyed for sequence variation by detailed restriction analysis. All Native American mtDNAs clustered into one of four distinct lineages, defined by the restriction site variants: HincII site loss at np 13,259, AluI site loss at np 5,176, 9-base pair (9-bp) COII-tRNA(Lys) intergenic deletion and HaeIII site gain at np 663. The HincII np 13,259 and AluI np 5,176 lineages were observed exclusively in Amerinds and were shared by all such tribal groups analyzed, thus demonstrating that North, Central and South American Amerinds originated from a common ancestral genetic stock. The 9-bp deletion and HaeIII np 663 lineages were found in both the Amerinds and Nadene but the Nadene HaeIII np 663 lineage had a unique sublineage defined by an RsaI site loss at np 16,329. The amount of sequence variation accumulated in the Amerind HincII np 13,259 and AluI np 5,176 lineages and that in the Amerind portion of the HaeIII np 663 lineage all gave divergence times in the order of 20,000 years before present. The divergence time for the Nadene portion of the HaeIII np 663 lineage was about 6,000-10,000 years. Hence, the ancestral Nadene migrated from Asia independently and considerably more recently than the progenitors of the Amerinds. The divergence times of both the Amerind and Nadene branches of the COII-tRNA(Lys) deletion lineage were intermediate between the Amerind and Nadene specific lineages, raising the possibility of a third source of mtDNA in American Indians.

Asian People↗
PubMed1992

Duration of obesity increases the incidence of NIDDM.

The effect of duration of obesity on incidence of non-insulin-dependent diabetes mellitus (NIDDM) was determined among Pima Indians. Duration of obesity was defined as the time since body mass index (BMI) was first known to be at least 30 kg/m2. Among 1057 participants eligible for study, there were 224 incident cases of NIDDM in 5975 person-yr of follow-up. The association of duration of obesity with incidence of diabetes adjusted for age, sex, and current BMI was highly significant (P less than 0.0001). This adjusted incidence of diabetes in cases/1000 person-yr of obesity was 24.8 for people with less less than 5 yr of obesity, 35.2 for people with 5-10 yr of obesity, and 59.8 for people with at least 10 yr of obesity. There was no apparent excess risk of diabetes for people who had a BMI of at least 30 kg/m2 and then lost weight. They had a slightly nonsignificantly higher rate than people who had not attained a BMI of at least 30 kg/m2 and a lower rate than people whose BMI remained 30-35 kg/m2. The relationship of duration of obesity with serum insulin concentrations among nondiabetic people was determined controlling for sex and age, BMI, and plasma glucose concentrations at the time of a glucose tolerance test. Duration of obesity was inversely associated with fasting serum insulin concentration through most of the range of fasting plasma glucose concentrations (P less than 0.001) and tended to be inversely associated with 2-h postload serum insulin concentration through the entire range of postload plasma glucose concentrations (P = 0.058).

Adolescent↗
PubMed1992

Insulin treatment, endogenous insulin concentration, and ECG abnormalities in diabetic Pima Indians. Cross-sectional and prospective analyses.

The prevalence and incidence of CHD, defined by ECG abnormalities according to the Tecumseh criteria for Minnesota Codes, were determined in Pima Indians greater than or equal to 25 yr of age. In a cross-sectional analysis, the age-sex-adjusted prevalence (+/- SE) of ECG abnormalities was higher in 1454 NIDDM patients (6.86 +/- 0.65%) than in 1696 nondiabetic subjects (3.23 +/- 0.63%; prevalence rate ratio = 2.12; 95% CI 1.39-3.25). In a prospective analysis, the age-sex-adjusted incidence (+/- SE) of ECG abnormalities was higher in 824 NIDDM patients (12.77 +/- 1.67) than in 935 nondiabetic subjects (5.93 +/- 1.43 cases/1000 person-yr; incidence rate ratio = 2.15; 95% CI 1.26-3.69). The prevalence of ECG abnormalities in insulin-treated NIDDM patients was significantly higher than in NIDDM patients not treated with insulin (age-sex-adjusted OR = 2.83; 95% CI 1.84-4.33); and this association persisted when adjusted for other factors such as sBP, BMI, duration of diabetes, serum cholesterol concentration, and oral hypoglycemic agents (OR = 2.12; 95% CI 1.34-3.37). In the prospective analysis, the incidence of ECG abnormalities in NIDDM patients treated with insulin was higher than in those NIDDM patients not treated with insulin, but, when controlled for age, sex, duration of diabetes, and oral hypoglycemic agents in a proportional-hazards model, the relationship with insulin treatment was not statistically significant (incidence rate ratio = 1.36; 95% CI 0.80-2.31). This suggests that insulin treatment may be a marker of more severe diabetes, and that factors associated with clinical indications for insulin treatment, rather than insulin treatment per se, are related causally to CHD. On the other hand, endogenous fasting and 2-h postload serum insulin concentrations were not associated with ECG abnormalities among 761 NIDDM patients not treated with insulin nor among 1226 nondiabetic subjects. Furthermore, in the prospective study, neither endogenous fasting nor 2-h postload serum insulin was associated with the subsequent development of ECG abnormalities in NIDDM patients or nondiabetic subjects.

Adult↗
PubMed1992

Impact of NIDDM on mortality and causes of death in Pima Indians.

OBJECTIVE: To compare overall and cause-specific death rates for diabetic and nondiabetic Pima Indians. RESEARCH DESIGN AND METHODS: This community-based study determined overall and cause-specific death rates in persons with and without NIDDM in the Pima population. Underlying causes of death for the 10-yr period from 1975 to 1984 were derived from review of death certificates and medical records. Diabetes diagnoses were based on an ongoing diabetes study initiated by the National Institutes of Health in 1965. RESULTS: Of the 512 deaths, 241 were in Pima Indians with NIDDM; 203 (84%) of the deaths in diabetic subjects were attributed to natural causes (46 diabetic nephropathy, 35 IHD, 29 infections, 20 malignant neoplasms, 20 alcoholic liver disease, 18 stroke, 35 other causes). For natural causes, the overall age-sex-adjusted death rate in diabetic subjects was 1.7 times (95% CI 1.4-2.2) that in nondiabetic subjects. Longer duration of diabetes was significantly related to mortality, an association that was stronger in women than in men. Rates of death from diabetic nephropathy, IHD, and infections (but not stroke) were each significantly related to longer diabetes duration. Together, diabetic nephropathy and IHD accounted for 90% of the excess death rate among diabetic, compared with nondiabetic, Pimas. CONCLUSIONS: In Pima Indians, NIDDM has a significant adverse effect on death rates that is directly related to diabetes duration, especially for deaths from diabetic nephropathy, IHD, or infections. Among the Pima, diabetic nephropathy is the leading cause of death, and IHD ranks second--a variation from other populations (in which IHD ranks first), probably partly attributable to a much younger age of onset of diabetes among the Pima than in the U.S. white population.

Adolescent↗
PubMed1992

Obesity in Pima Indians. Distribution characteristics and possible thresholds for genetic studies.

We examined distribution characteristics of the body mass index (BMI; weight/height; kg/m2) in a sample of 1128 male and 1372 female Pima Indians aged 15-65 years. We found that women had a higher mean and variance of BMI than men. From commingling analyses, we determined that the distribution of BMI could be accounted for either by a single skewed distribution or by a mixture of multiple normal components. These component distributions may be used to define provisional thresholds in selecting families for genetic studies. To ensure genetic segregation of obesity predisposing genes in Pima families will require that some members have BMIs > or = 40 kg/m2.

Adolescent↗
PubMed1992

The magnitude and origin of European-American admixture in the Gila River Indian Community of Arizona: a union of genetics and demography.

Complementary genetic and demographic analyses estimate the total proportion of European-American admixture in the Gila River Indian Community and trace its mode of entry. Among the 9,616 residents in the sample, 2,015 persons claim only partial Native American heritage. A procedure employing 23 alleles or haplotypes at eight loci was used to estimate the proportion of European-American admixture, m(a), for the entire sample and within six categories of Caucasian admixture calculated from demographic data, md. The genetic analysis gave an estimate of total European-American admixture in the community of 0.054 (95% confidence interval [CI] .044-.063), while an estimate from demographic records was similar, .059. Regression of m(a) on md yielded a fitted line m(a) = .922md, r = .959 (P = .0001). When total European-American admixture is partitioned between the contributing populations, Mexican-Americans have provided .671, European-Americans .305, and African-Americans .023. These results are discussed within the context of the ethnic composition of the Gila River Indian Community, the assumptions underlying the methods, and the potential that demographic data have for enriching genetic measurements of human admixture. It is concluded that, despite the severe assumptions of the mathematical methods, accurate, reliable estimates of genetic admixture are possible from allele and haplotype frequencies, even when there is little demographic information for the population.

Alleles↗