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Biomedical subjects

W C Knowler

Publications and source records attributed to W C Knowler.

At least 199 records · Page 11Linked to original sources
PubMed1988

Incidence of end-stage renal disease in type 2 (non-insulin-dependent) diabetes mellitus in Pima Indians.

The incidence of end-stage renal disease was determined in the Pima Indians of the Gila River Indian Community in Arizona, a population with a high prevalence of Type 2 (non-insulin-dependent) diabetes mellitus. Between 1975 and 1986, from a study population of 5059 subjects, end-stage renal disease occurred in 80 persons, 76 (95%) of whom had Type 2 diabetes. A review of the cases with end-stage renal disease indicated that among the diabetic subjects only two cases could be attributed to nondiabetic renal disease; all other cases were attributable to diabetic nephropathy. In diabetic Pima Indians the incidence rate of end-stage renal disease did not change during the study period, was similar in men and women, and was not effected by age at diagnosis of diabetes or by attained age, but did increase significantly with hypertension (p less than 0.05). The incidence of end-stage renal disease attributed to diabetic nephropathy increased from 0 cases/1000 person-years at 0-5 years to 40.8 cases/1000 person-years at greater than or equal to 20 years duration of diabetes. In these subjects with Type 2 diabetes, the incidence rate of end-stage renal disease was similar to that in subjects with Type 1 (insulin-dependent) diabetes who were followed at the Joslin Clinic in Boston, Massachusetts when those with similar duration of diabetes were compared.

Age Factors↗
PubMed1988

Medial arterial calcification and its association with mortality and complications of diabetes.

Medical arterial calcification was studied among 4,553 subjects in a 20-year, longitudinal study of Pima Indians. The prevalence and incidence of medial arterial calcification were highest among men, the elderly, and patients with Type 2 (non-insulin-dependent) diabetes mellitus. Medial arterial calcification was most commonly observed in the feet and appeared to progress proximally. Proportional hazards analysis was used to evaluate risk factors for medial arterial calcification in the feet and to evaluate medial arterial calcification as a risk factor for death and for complications of diabetes. Among diabetic patients, risk factors for medial arterial calcification were impaired vibration perception, long duration of diabetes, and high plasma glucose concentration (p less than 0.01 for each). Among nondiabetic subjects, age, male gender (p less than 0.01 for each), and high serum cholesterol concentration (p = 0.02) were risk factors for medial arterial calcification. Nondiabetic subjects with medial arterial calcification did not have higher mortality rates than subjects without medial arterial calcification (rate ratio = 0.95, 95% confidence interval = 0.7-1.3). Diabetic patients with medial arterial calcification, compared with diabetic patients without medial arterial calcification, had 1.5-fold the mortality rate (95% confidence interval = 1.0-2.1), 5.5-fold the rate of amputations (95% confidence interval = 2.1-14.1), 2.4-fold the rate of proteinuria (95% confidence interval = 1.3-4.5), 1.7-fold the rate of retinopathy (95% confidence interval = 0.98-2.8), and 1.6-fold the rate of coronary artery disease (95% confidence interval = 0.48-5.4).

Adolescent↗
PubMed1988

Relationship of glycosylated hemoglobin to oral glucose tolerance. Implications for diabetes screening.

The oral glucose tolerance test (OGTT) for diagnosis of diabetes is inconvenient and requires a great deal of patient cooperation. Glycosylated hemoglobin (GHb), an index of long-term glycemic control, could offer several practical advantages over the OGTT for diabetes screening. We evaluated GHb as a screen for diabetes in 381 adults from a population with a high prevalence of non-insulin-dependent diabetes (Pima Indians). All individuals underwent a standard OGTT (75 g) and were separated into one of three groups: normal (N), impaired glucose tolerance (IGT), or diabetes mellitus (D) based on World Health Organization criteria. HbA1c, a GHb, was measured by highly precise high-performance liquid chromatography (interassay C.V. less than 4%). The normal range for HbA1c was 4.07-6.03% based on the 95% confidence interval for a nondiabetic, mostly Caucasian population. Compared with OGTT, HbA1c was highly specific (91%); an elevated HbA1c usually indicated D or IGT (sensitivity = 85 and 30%, respectively). A normal HbA1c did not, however, exclude a diagnosis of D or IGT. Based on previous epidemiological studies relating plasma glucose to chronic diabetic complications, GHb as measured in this study would properly identify the vast majority of subjects at risk. Long-term studies are necessary to determine the actual risk of complications in individuals with persistently normal HbA1c and D or IGT (based on OGTT).

Adolescent↗
PubMed1988

Effect of proteinuria on mortality in NIDDM.

The effect of proteinuria (greater than or equal to approximately 1 g/day) on mortality in non-insulin-dependent diabetes mellitus (NIDDM) was assessed in Pima Indians aged greater than or equal to 45 yr. Among 1426 subjects, 48% with NIDDM at the beginning of followup, there were 489 deaths in 13,345 person-yr of observation. The age- and sex-adjusted mortality rate was 32.7/1000 person-yr (95% Cl = 27.6, 37.8) in diabetic subjects without proteinuria, similar to the rate of 30.1/1000 person-yr (95% Cl = 25.7, 34.4) in nondiabetic subjects without proteinuria. By contrast, in diabetic subjects with proteinuria the mortality rate was 121.4/1000 person-yr (95% Cl = 97.5, 145.3). When controlled for age, sex, and diabetes duration, diabetic subjects with proteinuria had a death rate 3.5 times as high (95% Cl = 2.8, 4.4) as those without proteinuria. Of the excess mortality associated with NIDDM in Pima Indians, 97% was found in subjects with proteinuria. The death rate in diabetic subjects without proteinuria was not appreciably greater than the rate in nondiabetic subjects. Mortality rates from uremia and cardiovascular disease were significantly higher in diabetic Pima Indians with proteinuria than in those without. These relationships are similar to observations reported in people with insulin-dependent diabetes.

Aged↗
PubMed1988

Congenital susceptibility to NIDDM. Role of intrauterine environment.

Non-insulin-dependent diabetes mellitus (NIDDM) during pregnancy in Pima Indian women results in offspring who have a higher prevalence of NIDDM (45%) at age 20-24 yr than in offspring of nondiabetic women (1.4%) or offspring of prediabetic women (8.6%), i.e., women who developed diabetes only after the pregnancy. These differences persist after taking into account paternal diabetes, age at onset of diabetes in the parents, and the offspring's weight relative to height. The findings suggest that the intrauterine environment is an important determinant of the development of diabetes and that its effect is in addition to effects of genetic factors.

Adolescent↗
PubMed1988

Lower-extremity amputations in NIDDM. 12-yr follow-up study in Pima Indians.

The incidence of lower-extremity amputations was estimated in the Pima Indians of the Gila River Indian Community in Arizona, a population with a high prevalence of non-insulin-dependent diabetes mellitus (NIDDM). Between 1972 and 1984, from a study population of 4399 subjects, lower-extremity amputations were performed on 84 patients, 80 (95%) of whom had NIDDM. Among diabetic subjects, the incidence rate of first lower-extremity amputations was higher in men than in women. Rates increased significantly with increasing duration of diabetes. Presence of medial arterial calcification, retinopathy, or nephropathy; absence of patellar tendon reflexes; impaired great toe vibration-perception threshold; and degree of fasting and 2-h postload hyperglycemia were significant risk factors for amputations. Serum cholesterol concentration, blood pressure, age, and absence of Achilles tendon reflexes were not predictive of amputations. The death rate was greater in diabetic amputees than in diabetic nonamputees of similar age, sex, and duration of diabetes, and a significant increase in cardiovascular deaths was observed in diabetic subjects with amputations. The incidence rate of lower-extremity amputations in diabetic Pima Indians is higher than that reported in other diabetic populations. This may reflect differences in risk or a more complete case ascertainment than was possible in previous studies. If the latter is true, the rate of amputations in diabetic individuals may be higher than has been previously appreciated.

Adolescent↗
PubMed1988

Gm3;5,13,14 and type 2 diabetes mellitus: an association in American Indians with genetic admixture.

In a sample of 4,920 Native Americans of the Pima and Papago tribes, there is a very strong negative association between the Gm haplotype Gm3;5,13,14 and type 2--or non-insulin-dependent--diabetes mellitus (prevalence ratio = 0.27, 95% confidence interval 0.18-0.40). One might conclude from this observation that the absence of this haplotype--or the presence of a closely linked gene--is a causal risk factor for the disease. It is shown that Gm3;5,13,14 is a marker for Caucasian admixture, and it is most likely the presence of Caucasian alleles and the concomitant decrease of Indian alleles that lowers the risk for diabetes, rather than the direct action of the haplotype or of a closely linked locus. This study demonstrates both the potential confounding effect of admixture on the interpretation of disease association studies and the importance of considering genetic admixture (or excluding individuals with genetic admixture) in studies of genetic markers of disease. The relationship between this admixture marker and the prevalence of diabetes also suggests a strong genetic component in the susceptibility to type 2 diabetes in Pima and Papago Indians.

Arizona↗
PubMed1988

Incidence, prevalence and risk factors for non-insulin-dependent diabetes mellitus.

Non-insulin-dependent diabetes is a worldwide disease. In the United States nearly 10 million persons are affected and the prevalence is increasing. Considerable advances in the understanding of the pathogenesis and determinants of non-insulin-dependent diabetes have occurred in recent years. Genetic and environmental determinants are associated with the development of diabetes, but the mode of inheritance of the genetic determinants is unknown. Obesity, particularly if it is centrally distributed and of long duration, is the most prominent environmental risk factor for non-insulin-dependent diabetes. Although it has long been suspected as an etiological factor, evidence that physical activity is a predictor of the disease is now emerging. The adoption of a western lifestyle and improvements in socioeconomic conditions are at least partially responsible for the very high rates of diabetes among several ethnic and racial groups, although the specific components of these changes that contribute to development of non-insulin-dependent diabetes are still uncertain. Other factors that worsen insulin resistance are likewise predictive of the development of disease. An understanding of the risk factors for non-insulin-dependent diabetes may lead to more specific intervention, and possibly to prevention of this disease.

Diabetes Mellitus, Type 2↗
PubMed1987

In vivo insulin action is familial characteristic in nondiabetic Pima Indians.

Non-insulin-dependent diabetes mellitus (NIDDM) is a genetic disorder characterized by two major pathogenic processes: reduced insulin action and a relative or absolute decrease in plasma insulin concentrations. We studied 116 nondiabetic siblings from 45 families to determine if in vivo insulin action showed any aggregation among siblings. Subjects were Pima Indians from the Gila River Indian Community in Arizona who, as a group, have the highest reported incidence and prevalence of NIDDM in the world. In vivo insulin action was determined by the euglycemic-clamp technique at two rates of insulin infusion in each subject with resulting mean plasma insulin concentrations of 119 and 1938 microU/ml. After adjustment for age, sex, and degree of obesity, there was significant aggregation among siblings of in vivo insulin action at the high insulin infusion rate (P less than or equal to .0001). Family membership independently accounted for approximately 34% of the variance in this measure of insulin action. Glucose uptake at the lower insulin infusion rate also showed familial aggregation (P less than .01), with family membership independently accounting for approximately 15% of the variance of this measurement. We conclude that in vivo insulin action is a familial characteristic. The familial component of insulin action occurs in addition to the effects of obesity, age, and sex on insulin action. Therefore it is not sufficient to simply know that an individual is lean or obese to predict his/her in vivo insulin resistance, because it must also be known whether he/she is from an insulin-resistant or insulin-sensitive family.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Prevalence of diabetes and impaired glucose tolerance and plasma glucose levels in U.S. population aged 20-74 yr.

The prevalence of physician-diagnosed diabetes and of undiagnosed diabetes and impaired glucose tolerance (IGT) that meet National Diabetes Data Group (NDDG) and World Health Organization (WHO) criteria have been estimated for the U.S. population aged 20-74 yr from the 1976-1980 National Health and Nutrition Examination Survey. This survey included a demographic/medical history questionnaire administered in the participant's home and a detailed examination composed of a physician's exam, special clinical procedures, other tests, and collection of blood and urine specimens. Survey participants were selected from 1970 census data through a stratified multistage probability sampling scheme. Of 17,390 eligible residents aged 20-74 yr, 15,357 (88.3%) participated in the interview and are the basis for estimates of diagnosed diabetes; 11,858 (68%) participated in the exam. A half sample of 5901 examinees was selected to receive a 75-g oral glucose tolerance test (OGTT) performed in the morning after an overnight 10- to 16-h fast. Of these examinees, valid OGTT data were obtained for 3772 people without a medical history of diabetes, and these are the basis for estimates of undiagnosed diabetes and IGT. The major reasons for incomplete OGTT data were inability of participants to attend the examination center in the morning and lack of adherence to the fasting instructions. Despite the relatively low response rates, evidence is presented that data on both the interviewed sample and those receiving the OGTT, when adjusted for the 1970-1980 census characteristics by age, race, sex, income, and geographic location, are representative of the U.S. population. Extrapolation of these data to the U.S. population aged 20-74 yr indicates a total diabetes prevalence of 6.6% by NDDG criteria, or more than 8 million people with diabetes. The prevalence of undiagnosed diabetes (3.2%) was almost equal to that of previously diagnosed diabetes (3.4%). Total rates of diabetes increased with age, from 2.0% at age 20-44 yr to 17.7% at age 65-74 yr. Rates were approximately equal by sex but were greater in Blacks than in Whites. The prevalence of undiagnosed diabetes by WHO criteria (3.4%) was similar to that by NDDG criteria, but the rate of impaired glucose tolerance (11.2%) was more than twice the NDDG estimate (4.6%). Both obesity and parental history of diabetes were associated with significantly higher rates of diabetes and IGT. Fasting plasma glucose was relatively insensitive to age, but 1-h and 2-h post-75-g glucose values increased significantly with age.

Adult↗
PubMed1986

Familial dependence of the resting metabolic rate.

Human obesity is known to be a familial disorder. We studied 130 nondiabetic adult southwestern American Indians (74 men and 56 women) from 54 families to determine whether the resting metabolic rate, as measured by indirect calorimetry, is a familial trait that is independent of individual differences in fat-free mass (estimated mass of metabolically active tissue), age, and sex. We found that most of the variance in the resting metabolic rate (83 percent, P less than 0.0001) was accounted for by three covariates--fat-free mass, age, and sex--and that fat-free mass was the most important determinant. Family membership accounted for an additional 11 percent (P less than 0.0001) of the variance in the resting metabolic rate. Thus, resting metabolic rate is a familial trait in this population, and it is independent of differences in fat-free mass, age, and sex. We also found that persons from families with lower resting metabolic rates were no more obese than persons from families with higher metabolic rates. This finding may be partly explained by the close correlation between fat-free mass and percentage of body fat (r = 0.81, P less than 0.0001), which indicates that the resting metabolic rate, as adjusted for fat-free mass, is already partly adjusted for obesity. Only prospective studies will elucidate whether the familial dependence of the resting metabolic rate is a contributing mechanism to the familial predisposition to obesity.

Adolescent↗
PubMed1986

Gm 3;5,13,14 and stated-admixture: independent estimates of admixture in American Indians.

Bernstein's formula for the estimation of the amount of admixture (m) in a hybrid population has been used frequently since its publication in 1931. While mathematically correct, it has not been shown to be correct in practice, because an independent estimate from a large sample has not been available. We have compared the estimate of m for Caucasian admixture derived by using Bernstein's formula with that estimated from stated-admixture (Sa) within a sample of 5,759 Native Americans. There was a linear relationship between the two variables (m = -.000275 + .714Sa; r = .976 for the grouped data, P = .0001).

Gene Frequency↗
PubMed1985

Incidence of cataract extraction in Pima Indians. Diabetes as a risk factor.

The incidence of visually disabling cataract was estimated by the rate of first cataract extraction in a population of Pima Indians in Arizona. The annual age-specific rates of cataract surgery (first and second eyes) were 3.7 to 5.9 times as high as the estimated US rates. Diabetes was a strong risk factor for first cataract surgery in all age and sex groups except in men aged 75 to 84 years. Overall, with age and sex controlled, the rate of first cataract surgery was 2.2 times as high (95% confidence interval, 1.3 to 3.9) in diabetic as in nondiabetic subjects. Cataract surgery was related to the duration and type of treatment of diabetes. Insulin-treated diabetics had about five times the rate of those with normal glucose tolerance. The rate of cataract surgery was lowest in subjects with normal glucose tolerance, somewhat higher in those with impaired glucose tolerance, and even higher with increasing duration of diabetes.

Adult↗
PubMed1985

GM allotypes in Native Americans: evidence for three distinct migrations across the Bering land bridge.

We report the results of typings, for immunoglobulin G allotypes, of 5392 Native Americans from ten samples, the typings having been performed over the last 20 years. Four cultural groups are represented: the Pimans-Pima and Papago; the Puebloans-Zuni and Hopi; the Pai-Walapai; and the Athabascans-Apache and Navajo. The haplotype Gm1;21 has the highest frequency in each population while Gm1,2;21 is polymorphic in all except the Hopi. The Mongoloid marker Gm1;11,13 is found primarily in the Athabascans. The Caucasian haplotype Gm3;5,11,13 is found at polymorphic frequencies in several of the populations but its frequency is very low or absent among nonadmixed individuals. Although Nei's standard genetic distance analysis demonstrates genetic similarity at the Gm and Km loci, the heterogeneity that does exist is consistent both with what is known about the prehistory of Native Americans and traditional cultural categories. When the current Gm distributions are analyzed with respect to the three-migration hypothesis, there are three distinct Gm distributions for the postulated migrants: Gm1;21 and Gm1,2;21 for the Paleo-Indians 16,000 to 40,000 years ago; Gm1;21, Gm1,2;21, and Gm1;11,13 for the second wave of Na-Dene hunters 12,000 to 14,000 years ago; and Gm1;21 and Gm1;11,13 for the Eskimo-Aleut migration 9,000 years ago. The Pimans, Puebloans, and the Pai are descendents of the Paleo-Indians while the Apache and Navajo are the contemporary populations related to the Na-Dene. Finally, the Gm distribution in Amerindians is found to be consistent with a hypothesis of one migration of Paleo-Indians to South American, while the most likely homeland for the three ancestral populations is found to be in northeastern Asia.

Chromosome Mapping↗
PubMed1985

Dramatic founder effects in Amerindian mitochondrial DNAs.

Southwestern American Indian (Amerindian) mitochondrial DNAs (mtDNAs) were analyzed with restriction endonucleases and found to contain Asian restriction fragment length polymorphisms (RFLPs) but at frequencies very different from those found in Asia. One rare Asian HincII RFLP was found in 40% of the Amerindians. Several mtDNAs were discovered which have not yet been observed on other continents and different tribes were found to have distinctive mtDNAs. Since the mtDNA is inherited exclusively through the maternal lineage, these results suggest that Amerindian tribes were founded by small numbers of female lineages and that new mutations have been fixed in these lineages since their separation from Asia.

Asia↗
PubMed1985

Relationship between insulin-mediated glucose disposal and lipid metabolism in man.

To assess the possible effects of lipid metabolism on insulin-mediated glucose disposal, 18 nondiabetic Pima Indian women (age 18-35 yr) were studied using 1-14C-palmitate infusion to measure free fatty acid turnover rate followed by a euglycemic clamp (clamp) to measure in vivo insulin-mediated glucose disposal (M). Indirect calorimetry was performed in the basal state and during the clamp. This was used to assess glucose oxidation rate, lipid oxidation rate, and to calculate nonoxidative glucose disposal (storage). Basal and clamp lipid oxidation rate correlated with basal plasma free fatty acid concentration (r = 0.81, P less than or equal to 0.0001, r = 0.67, P less than 0.003, respectively). The fall in lipid oxidation was highly correlated with the increase in glucose oxidation during the insulin infusion (r = 0.96, P less than or equal to 0.0001). The clamp lipid oxidation rate negatively correlated with the glucose oxidation rate (r = -0.85, P less than 0.0001) and with the M value (r = -0.60, P less than 0.01) but was not correlated with the clamp glucose storage (r = -0.2, P = 0.4). On the other hand, glucose storage appeared to make a greater contribution to the difference in M value between the upper and lower extremes of M than did glucose oxidation, as evidenced by an increase in glucose storage of 0.59 mg/kg fat-free mass times minute per 1 mg/kg fat-free mass times minute increase in glucose disposal. The M value was negatively correlated with obesity as measured by percent body fat (r = -0.64, P less than 0.004), but neither basal free fatty acid concentration, basal free fatty acid turnover, basal lipid oxidation, nor clamp lipid oxidation correlated with percent body fat. We conclude that an interaction of lipid and glucose metabolism in a glucose fatty acid cycle, as proposed by Randle et al. (1), may be operative in the regulation of glucose oxidation in man. The disposal of glucose however has two components. The storage component does not appear to be associated with lipid oxidation in the way that the oxidative component is and may be regulated by a different mechanism. Since the results show that the glucose storage component plays a significant role in distinguishing between those with low and high M values, we suggest that the glucose fatty acid cycle can, at best, only partially explain impaired in vivo insulin-mediated glucose disposal. Furthermore, the data suggest that the impact of obesity on in vivo insulin resistance appears to be mediated by factors other than changes in lipid availability or metabolism.

Adolescent↗
PubMed1985

Gestational diabetes mellitus and impaired glucose tolerance during pregnancy. Long-term effects on obesity and glucose tolerance in the offspring.

The effects of disturbances in carbohydrate metabolism during gestation were studied in the offspring of 1049 Pima Indian women who had no previous diagnosis of diabetes. Rates of fetal and maternal complications of pregnancy among women with diabetes first diagnosed during the pregnancy were similar to those among women in whom diabetes was recognized before gestation. Offspring, aged 5-19 yr, of women with abnormal glucose tolerance during pregnancy had a higher mean percent desirable weight and a higher mean postchallenge plasma glucose concentration than did offspring of women with normal glucose tolerance. Percent desirable weight and glucose concentration, however, were both lower than found in offspring of women with diabetes diagnosed before the pregnancy. Thus, metabolic events during pregnancy, as indicated by the detection of abnormal glucose tolerance during gestation, appear to have long-term effects on obesity and glucose tolerance in the offspring.

Adolescent↗