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Biomedical subjects

W C Knowler

Publications and source records attributed to W C Knowler.

234 records · Page 13Linked to original sources
PubMed1979

Islet cell antibodies and diabetes mellitus in Pima Indians.

Pancreatic islet cell antibodies and 12 other autoantibodies were measured at the time of diabetes diagnosis in 46 Pima Indians, aged 17--47 years, and in 46 age-sex matched non-diabetic controls. Islet cell antibodies were found in only two diabetics, aged 20 and 25, compared with none of 46 controls. Neither of the subjects with islet cell antibodies had other autoantibodies. At least one type of autoantibody was found in 14 (30%) of the diabetics and in 14 controls, but none was significantly associated with diabetes. This study indicates that diabetes in the Pima Indians, even those with an onset below 25 years of age, is almost entirely of type II, in that the disease is not associated with islet cell antibodies, ketoacidosis, or insulin dependence.

Adolescent↗
PubMed1978

Sex differences in the size of bile acid pools.

In view of the excess prevalence of gallstones among women and the association of gallstones with diminished bile acid pool size, we measured bile acid pools in 27 male and 25 female healthy human volunteers. The average bile acid pool in the women was significantly smaller than in the men (2.25 +/- .12 g versus 2.88 +/- .16 g; p = 0.003). Chenodeoxycholic acid pool size, computed from bile acid composition data available in 43 of these subjects, was also smaller in women than men (0.94 +/- 0.06 versus 1.22 +/- 0.07 g; p = 0.004). Age, race, and body size bore no statistically significant relationship to bile acid pool size. Biliary cholesterol saturation was positively correlated with weight and obesity and showed a significant inverse correlation with chenodeoxycholic acid pool size, but not with total bile acid pool size. These findings suggest a possible mechanism for the higher prevalence of gallstones among women.

Adolescent↗
PubMed1978

Diabetes incidence and prevalence in Pima Indians: a 19-fold greater incidence than in Rochester, Minnesota.

The incidence and prevalence of diabetes mellitus were determined in 3733 Pima Indians aged 5 years or over by periodic examinations over a 10-year period. The examinations included modified glucose tolerance tests and medical record review. The age-sex adjusted prevalence rate was 21.1% (SE = 0.7%). Prevalence was low in childhood and plateaued at 40--50% in adults over 35 years of age. The age-sex adjusted incidence rate of 26.5 cases/1000 person-years (SE = 1.9) is the highest reported diabetes incidence known to the authors. Incidence increased from low levels in childhood to peak at age 40 (males) or 50 (females) and then gradually declined. Diabetes incidence was 19 times that in the predominantly white population of Rochester, Minnesota (95% confidence interval, 16 to 22 times). The high incidence rate was found despite using a more stringent diagnostic criterion than customarily employed, and was shown not be due to biased follow-up of subjects.

Adolescent↗
PubMed1977

Visual lung-sound characterization by time-expanded wave-form analysis.

To characterize lung sounds objectively, we examined, by means of time-amplitude plots, selected tape recordings of auscultatory phenomena considered by six observers to be typical of those in a standard classification. Normal lung sounds could not consistently be visually distinguished from adventitious sounds at conventional chart recorder speeds of 100 mm per second or less, but the differentiation was easily achieved when the time scale of the plots was raised to 800 mm per second. When discontinuous sounds (rales, crackles or crepitations) were heard clinically, the time-expanded wave forms showed intermittent "discontinuous" deflections usually less than 10 msec in duration. When continuous sounds (rhonchi or wheezes) were heard, the deflections were usually more than 250 msec. Time-expanded wave form analysis provides reproducible visual displays that allow documentation of the differentiating features of lung sounds and enhances the diagnostic utility of the sounds.

Auscultation↗
PubMed1975

Behavioral activities and cardiovascular functions. II. Effects of sustained static work in squirrel monkeys.

Mean arterial blood pressure (MABP) and heart rate (HR) were measured in unanesthetized squirrel monkeys trained to sustain for 20 seconds a forceful downward pull on an inverted T-bar. The MABP change during the strong static contraction of skeletal muscles involved in the pull was polyphasic, consisting of a brief initial rise and fall followed by a rise to a level above resting values which was sustained. At the end of the pull, the pressure fell transiently below the resting level. HR was elevated throughout the pull, returning towards the resting value in the minute following the pull. After hexamethonium, which reduced the resting MABP from about 120 mm Hg to about 80 mm Hg, the fall in MABP following the initial rise was enhanced, the level sustained through the pull was less than the resting level, and MABP fell still lower following the end of the pull. Phentolamine caused similar changes. Hexamethonium reduced the resting HR and abolished the HR changes during pulling. Raising the MABP after hexamethonium with phenylephrine further enhanced the falls in pressure during and following the pull. It is concluded that the polyphasic MABP changes to pulling involve direct mechanical effects of contracting skeletal muscle (responsible for the initial rise and contributing to the sustained rise), sympathetic vasoconstrictor discharge (contributing to the sustained rise and opposing the falls in MABP during and after the pull) and vasodilatation in active skeletal muscle (opposing the sustained rise during the pull and causing the fall after the pull). Although the participation of these factors in cardiovascular responses to exercise are generally well recognized, comparison of the patterns of response in rhesus and squirrel monkeys reveals large quantitative differences in the contributions of different factors and emphasizes again the caution that should be exercised in inferring direct environmental, emotional or conditioning effects on cardiovascular function.

Acoustic Stimulation↗
PubMedDate not supplied

Effect of diabetes in pregnancy on offspring: follow-up research in the Pima Indians.

OBJECTIVE: To review data on the long-term effects of prenatal exposure to the diabetic intrauterine environment in the Pima Indians of Arizona. This population has high rates of Type 2 diabetes mellitus that has a strong genetic component and develops at young ages. METHODS: Since 1965, Pima Indians at least 5 years old participated in a study of diabetes and its complications. This study consisted of biennial examinations with measurements of obesity and glucose tolerance and of glucose tolerance testing during pregnancy. The longitudinal nature of the study has permitted comparisons of data collected on children and young adults whose mothers were tested during pregnancy. RESULTS: Offspring of women who had diabetes during pregnancy were more obese and had a higher prevalence of Type 2 diabetes. Exposure to the diabetic intrauterine environment was responsible for about 40% of Type 2 diabetes in 5-19-year-old children between 1987 and 1996--approximately twice the attributable risk found between 1967 and 1976. Over 70% of persons with prenatal exposure have Type 2 diabetes at 25-34 years of age. CONCLUSIONS: The effects of the diabetic pregnancy can be thought of as a vicious cycle, with consequences for the offspring extending well beyond the neonatal period. The young woman whose mother had diabetes during pregnancy is at risk of perpetuating the cycle by developing diabetes by her childbearing years. In this population, much of the increase in childhood Type 2 diabetes can be attributed to the diabetic intrauterine environment, which may be a factor in the alarming rise of this disease nationally.

Adolescent↗
PubMedDate not supplied

Family and genetic studies of indices of insulin sensitivity and insulin secretion in Pima Indians.

BACKGROUND: The present analyses were conducted to examine the extent to which insulin sensitivity and insulin secretion, assessed using simple indices derived from an oral glucose tolerance test, are influenced by genetic factors, and to assess whether these genetic factors overlap with those influencing susceptibility to type 2 diabetes in Pima Indians. METHODS: Indices calculated from fasting and 2-h post-load insulin (I(0), I(120)) and glucose (G(0), G(120)) concentrations included insulin sensitivity index [ISI(0)=10(4)/(I(0).G(0))] and corrected insulin response [CIR(120)=I(120)/[G(120).(G(120)-70 mg/dl)]]. Heritability (h(2)) was determined using variance components methods in 1421 non-diabetic individuals from 446 sibships. Among 595 individuals in 186 sibships, genome-wide quantitative trait linkage analyses of ISI(0) and CIR(120) were conducted and affected-sibling analyses of diabetic siblings stratified by prediabetic measurements of ISI(0) and CIR(120) were also performed. RESULTS: Both ISI(0) (h(2)=0.37+/-0.06) and CIR(120) (h(2)=0.25+/-0.07) were moderately heritable. Modest evidence for linkage with CIR(120) (logarithm of odds (LOD)=1.6) was observed on chromosome 1q in a region previously shown to have linkage with young-onset diabetes in Pimas. When diabetic siblings were stratified by CIR(120), evidence for linkage in this region was strongest (LOD=1.5) among those with a low CIR(120). Additional regions with modest evidence for linkage with ISI(0) were observed on chromosomes 9p (LOD=2.0) and 14p (LOD=1.7). CONCLUSIONS: The present analyses suggest that insulin sensitivity and insulin secretion are influenced by genetic factors in Pima Indians. The linkage analyses suggest that the putative diabetes-susceptibility gene on chromosome 1q affects insulin secretion. Published in 2001 by John Wiley & Sons, Ltd.

Arizona↗
PubMedDate not supplied

Prediabetic blood pressure and familial predisposition to renal disease in Pima Indians with non-insulin-dependent diabetes mellitus.

Renal disease is a frequent complication of non-insulin-dependent diabetes in the Pima Indians from the Gila River Indian Community in Arizona. This review describes the relationship between prediabetic blood pressure and the subsequent development of renal disease, and characterizes the familial aggregation of diabetic renal disease in this population.

Albuminuria↗
PubMedDate not supplied

Genealogy construction in a historically isolated population: application to genetic studies of rheumatoid arthritis in the Pima Indian.

PURPOSE: Due to the characteristics of complex traits, many traits may not be amenable to traditional epidemiologic methods. We illustrate an approach that defines an isolated population as the "unit" for carrying out studies of complex disease. We provide an example using the Pima Indians, a relatively isolated population, in which the incidence and prevalence of Type 2 diabetes, gallbladder disease, and rheumatoid arthritis (RA) are significantly increased compared with the general U.S. population. A previous study of RA in the Pima utilizing traditional methods failed to detect a genetic effect on the occurrence of the disease. METHODS: Our approach involved constructing a genealogy for this population and using a genealogic index to investigate familial aggregation. We developed an algorithm to identify biological relationships among 88 RA cases versus 4,000 subsamples of age-matched individuals from the same population. Kinship coefficients were calculated for all possible pairs of RA cases, and similarly for the subsamples. RESULTS: The sum of the kinship coefficient among all combination of RA pairs, 5.92, was significantly higher than the average of the 4,000 subsamples, 1.99 (p < 0.001), and was elevated over that of the subsamples to the level of second cousin, supporting a genetic effect in the familial aggregation. The mean inbreeding coefficient for the Pima was 0.00009, similar to that reported for other populations; none of the RA cases were inbred. CONCLUSIONS: The Pima genealogy can be anticipated to provide valuable information for the genetic study of diseases other than RA. Defining an isolated population as the "unit" in which to assess familial aggregation may be advantageous, especially if there are a limited number of cases in the study population.

Arizona↗
PubMedDate not supplied

Plasma and lipoprotein cholesterol and triglyceride in the Pima Indian population. Comparison of diabetics and nondiabetics.

Lipoprotein cholesterol and triglyceride concentrations were compared in diabetic and nondiabetic Pima Indians, a homogeneous population with a high occurrence of noninsulin-dependent diabetes mellitus. Data were available on 690 subjects with diabetes or impaired glucose tolerance. Total and very low density lipoprotein (VLDL) triglycerides were approximately 150% of the nondiabetic values, but very few diabetics had pronounced hypertriglyceridemia. Significant elevations in low density lipoprotein (LDL) triglyceride were also observed in diabetic men and women of all ages. Decreases in high density lipoprotein (HDL) cholesterol were similar in diabetic men and women, and the differences in HDL cholesterol were much greater in less obese individuals. Changes in HDL in the diabetics were reflected in all three subfractions, HDL2b, HDL2a, and HDL3. Both total and LDL cholesterol were elevated in diabetic women, but not in diabetic men. Thus, there were greater changes in lipoprotein distribution in diabetic women. When multiple regression analysis was performed to examine the relationships in diabetics between lipoproteins and other variables, plasma glucose appeared to be the variable most closely associated with plasma lipoproteins in diabetics (positive with VLDL and LDL, negative with HDL). In diabetics, obesity was correlated with HDL but not VLDL, whereas alcohol consumption appeared to be associated with VLDL but not HDL.

Adolescent↗
PubMedDate not supplied

Obesity in offspring of diabetic Pima Indian women despite normal birth weight.

The relationships of birth weight and maternal diabetes to the development of obesity were examined at 5-19 yr of age in the offspring of Pima Indian women. At each age, offspring of diabetic women, even those who were of normal birth weight, had a higher mean weight relative to height than offspring of nondiabetic and prediabetic women. Birth weight was predictive of relative weight in 5- to 9- and 10- to 14-yr-old offspring of nondiabetic women but not in the oldest group. In contrast, for offspring of prediabetic and diabetic women, birth weight was not predictive of subsequent obesity at any age studied. Offspring of diabetic women were heavier than offspring of nondiabetic and prediabetic women regardless of birth weight. Thus, maternal diabetes was important in predicting body size in the offspring even after accounting for the effects of the birth weight and maternal body size.

Adolescent↗
PubMedDate not supplied

Diabetes mellitus and its vascular complications in Japanese migrants on the Island of Hawaii.

Japanese migrants and their offspring on the island of Hawaii and Japanese living in Hiroshima were examined for diabetes mellitus and its vascular complications. the same methods and investigators were used in both locations. Death certificates of Japanese and Caucasians dying on the island during the past 26 yr were analyzed. Diabetes, defined as a venous serum glucose concentration of at least 200 mg/dl 2 h after a 50-g oral glucose load, was significantly more common in the Hawaiian Japanese than in the Hiroshima Japanese subjects. This suggests that diabetes is more prevalent in Japanese in Hawaii than in Japan, although lack of knowledge about the total population of Japanese migrants in Hawaii makes this generalization uncertain. The proportion of deaths attributed to diabetes was much higher in Japanese migrants and their offspring in Hawaii than in Japan. During the 1950s, the proportional death rate from diabetes was about half as large in Japanese Hawaiians as in Caucasian Hawaiians, but it increased to become 1.6 times the Caucasian rate during the 1970s. A nutritional study revealed that the total caloric intake was similar in Japanese in Hawaii and Hiroshima, although the estimated level of physical activity was less in the Hawaiian subjects. Consumption of animal fat and simple carbohydrates (sucrose and fructose) were at least twice as high in Hawaiian as in Hiroshima Japanese. Conversely, Hiroshima Japanese consumed about twice the amount of complex carbohydrate as the Hawaiian Japanese. These observations support the hypothesis that a high fat, high simple carbohydrate, low complex carbohydrate diet and/or reduced levels of physical activity increase risk of diabetes. The proportion of deaths attributed to ischemic heart disease was higher in both diabetic and nondiabetic Japanese Hawaiians than in diabetic subjects in Japan. The rates were similar for Japanese and Caucasians in Hawaii. There was no evidence of an environmental influence on the development of microangiopathy (retinopathy) in diabetes, as the prevalence of diabetic retinopathy (stratified for diabetes duration) was similar in Japanese subjects in Hawaii and in Japan, and it was similar to previous reports from England. On the other hand, diabetes alone did not appear to account for the greater prevalence of macroangiopathy in Hawaiian Japanese than in Hiroshima. Thus environmental factors, possibly including diet, appear to be involved in the development of macrovascular complications of diabetes.

Adult↗
PubMedDate not supplied

Gestational diabetes: infant and maternal complications of pregnancy in relation to third-trimester glucose tolerance in the Pima Indians.

A modified oral glucose tolerance test was done during the third trimester in 811 pregnancies in Pima Indian women over a 13-yr period, and maternal and fetal complications were documented. Diabetes was known to be present in 51 pregnancies. Among those who were not previously known to have diabetes, rates of perinatal mortality, macrosomia, toxemia, and cesarean section varied directly with glucose concentration, but congenital malformation and prematurity rates did not. Rates of all of these complications were higher in known diabetic women than in the remainder of the population. In addition to glucose concentrations, maternal weight and age were predictive of macrosomia and toxemia. Third-trimester glucosuria was found to be of very limited value as a screening procedure for gestational diabetes. In 233 women followed for 4-8 yr, the third-trimester glucose concentration was highly predictive of the subsequent incidence of diabetes.

Adult↗
PubMedDate not supplied

International criteria for the diagnosis of diabetes and impaired glucose tolerance.

International agreement on classification and criteria for the diagnosis of diabetes is highly desirable. Two systems promulgated in 1979-80 and widely used today are those of the NIH National Diabetes Data Group (NDDG) and of the World Health Organization (WHO). Although these systems are similar in many ways, certain discrepancies between them result in different classifications of oral glucose tolerance test (OGTT) results and different estimates of prevalence of the various glucose tolerance groups. Analysis of 3704 OGTTs performed during a survey of a national probability sample of U.S. residents without known diabetes and aged 20-74 yr shows that the two systems agreed in classification of 87.7% of OGTTs. For the remainder, the NDDG and WHO classifications differed, primarily because nondiagnostic OGTTs occur in the NDDG system but not in the WHO system. The differences resulted in the prevalence of impaired glucose tolerance (IGT) using WHO criteria (11.6%) being more than twice that using NDDG criteria (4.9%), although prevalence rates of diabetic OGTTs were similar in both systems (3.6%, 3.4%). The WHO system represents a simpler, inclusive classification scheme, and there is insufficient evidence from longitudinal studies of prognostic differences that would justify the more complicated NDDG diagnostic criteria. In situations where multiple venipunctures or retesting are not possible, the venous plasma glucose concentration at 2 h after 75 g glucose appears to be the most appropriate single value to use to designate whether a person has diabetes, IGT, or neither. The use of this value alone placed 97% of diabetic subjects and all other subjects, in the same class they were in when the full WHO criteria were used.

Adult↗