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Biomedical subjects

W C Knowler

Publications and source records attributed to W C Knowler.

At least 217 records · Page 12Linked to original sources
PubMed1985

Measurement of glycosylated whole-blood protein for assessing glucose control in diabetes: collection and storage of capillary blood on filter paper.

We present data on the use of filter-paper blood collection for measurement of glycosylated whole-blood proteins (gWB) (hemoglobin and plasma proteins). A capillary blood sample, obtained by fingerprick, is spotted directly onto filter paper (Schleicher & Schuell 903). The blood spot is washed briefly with alcohol (ethanol or isopropanol) to remove free glucose and dried before shipment to the laboratory. In the laboratory, the blood is eluted from the paper and analyzed for gWB by a colorimetric method. The gWB is primarily a measure of glycosylated hemoglobin (gHb) with a small contribution from glycosylated plasma protein. Concentrations of gWB and gHb are highly correlated (r = 0.91). The filter-paper method offers advantages over currently available methods for quantifying gHb and may be particularly useful in screening for diabetes and for assessing glycemic control in patients from remote areas.

Blood Proteins↗
PubMed1984

Polymorphism in the 5' flanking region of the human insulin gene. Relationships with noninsulin-dependent diabetes mellitus, glucose and insulin concentrations, and diabetes treatment in the Pima Indians.

Variations in DNA sequences flanking the insulin gene were studied in relation to noninsulin-dependent diabetes mellitus (NIDDM) in 87 unrelated Pima Indians at least 35 yr of age. DNA was isolated from nuclei of peripheral blood leukocytes and digested with restriction endonucleases. Less variation in this region was found in Pima Indians than in other racial groups previously studied. Only two classes of alleles (classes 1 and 3) were found, and there was virtually no variation within classes. At least one class 3 allele was found in 47% of the 38 nondiabetic subjects and in 37% of the 49 with NIDDM (odds ratio = 0.65, P = 0.4, 95% confidence interval for the odds ratio = 0.25 to 1.67). Homozygosity for class 3 alleles, however, was found only in diabetics. There were no differences according to genotype in obesity, fasting or postload glucose or insulin concentrations, or in the relationships between insulin and glucose concentrations. 61% (11/18) of the diabetics with a class 3 allele were receiving drug treatment for diabetes compared with only 26% (8/31) of diabetics without a class 3 allele (P = 0.03). The insulin gene polymorphism probably plays no important role in the genesis of NIDDM in Pima Indians, nor does it influence the glucose or insulin concentrations or their relationship to each other, but the class 3 allele, especially when homozygous in this population, may influence the severity of the disease as indicated by need for drug treatment.

Adult↗
PubMed1983

Excessive obesity in offspring of Pima Indian women with diabetes during pregnancy.

We studied the relation in Pima Indians between obesity in children and diabetes during pregnancy in their mothers. Sixty-eight children of 49 women who had had diabetes during pregnancy had a higher prevalence of obesity than 541 children of 134 women who subsequently had diabetes (prediabetics) or than 1326 children of 446 women who remained nondiabetic. At 15 to 19 years of age, 58 per cent of the offspring of diabetics weighed 140 per cent or more of their desirable weight, as compared with 17 per cent of the offspring of nondiabetics and 25 per cent of those of prediabetics (P less than 0.001). Obesity in the offspring was directly related to maternal diabetes, since the association was not substantially confounded by maternal obesity. The findings strongly suggest that the prenatal environment of the offspring of diabetic women results in the development of obesity in childhood and early adulthood.

Adolescent↗
PubMed1983

Polymorphism in the 5' flanking region of the human insulin gene: a genetic marker for non-insulin-dependent diabetes.

We sought to determine whether differences in the human insulin gene or its immediate flanking sequences could be found in diabetes. Peripheral leukocyte DNA from 217 unrelated persons, including blacks, whites, and Pima Indians, was analyzed by restriction-enzyme digestion, blotting to nitrocellulose filters, and hybridization to cloned [32P]insulin-gene probes. A region of length variation including deletions (0.1 to 0.2 kilobase pairs) or insertions (0.6 to 5.5 kb) of DNA was found only in the immediate 5' flanking region in 33 per cent of the genes examined. A 1.6-kb insertion accounted for 80 per cent of the polymorphism. This variant was found more often in subjects with non-insulin-dependent diabetes than in nondiabetics, regardless of race (P = 0.011). Length polymorphism in the 5' flanking region of the insulin gene may provide a genetic marker for non-insulin-dependent diabetes.

Adolescent↗
PubMed1983

Diabetes mellitus in the Pima Indians: genetic and evolutionary considerations.

Non-insulin-dependent diabetes mellitus is a common disease in the Pima Indians. It is familial and strongly related to obesity. Neel (1962) suggested that the introduction of a steady food supply to people who have evolved a "thrifty genotype" leads to obesity, insulin resistance, and diabetes. Our findings in the Pimas of differences in insulin sensitivity in different metabolic pathways suggest that the thrifty genotype involves the ability of insulin to maintain fat stores despite resistance to glucose disposal. The recent increase in diabetes incidence following the availability of an abundant food supply suggests that the ability to store energy efficiently during cycles of feast and famine may now lead to obesity, insulin resistance, and diabetes.

Adolescent↗
PubMed1983

HLA and B-lymphocyte alloantigens in Gila River Indians.

HLA-A, B, C, DR, and MB and MT B-lymphocyte alloantigens were tested in 249 Pima and Papago Indians from Arizona. Frequencies of A and B locus antigens in Pimas were similar to published values for other North American Indians, as well as previous reports from Pimas. Cw3 was the most frequent C locus antigen found and DR5 was the most frequent DR antigen. Another B-cell specificity, DuB31, behaved as a DR allele and had a phenotype frequency of .717. This study is the first report of MB and MT frequencies in a North American Indian population, and the pattern of association with some DR antigens appears to be different from that observed in Europeans. MT3 had a phenotype frequency of .583, but was not associated with DR4, 7, 9, which suggests an undefined DR allele associated with MT3.

Adolescent↗
PubMed1983

Plasma and lipoprotein cholesterol and triglyceride concentrations in the Pima Indians: distributions differing from those of Caucasians.

Plasma and lipoprotein cholesterol and triglyceride concentrations were measured in Pima Indians, a genetically homogeneous population with a high prevalence of obesity and diabetes and a low frequency of coronary heart disease. The data for nondiabetic Pima Indians were compared with those of U.S. Caucasians measured during the Lipid Research Clinics Prevalence Study. Plasma total and low-density lipoprotein (LDL) cholesterol levels in Pima men older than 30 years of age and in women over 25 were lower than those of U.S. Caucasians, and in men the total and LDL cholesterol levels did not increase with age. In Pima male subjects of all ages high-density lipoprotein (HDL) cholesterol levels were lower than that in Caucasian male subjects, and in Pima female subjects HDL cholesterol levels averaged 11 mg/dl lower than those in female Caucasian subjects. On the other hand, plasma triglyceride levels in Pima male subjects up to 35 years of age and in female subjects up to 55 years old were higher than those of Caucasians. Comparison of plasma cholesterol and triglyceride levels in Pima male and female subjects showed the same relationships as those in Caucasians (i.e., higher in male subjects until the older age groups), but Pima male and female subjects had similar HDL cholesterol levels. There was a strong negative correlation between obesity and HDL cholesterol levels in Pimas. Obesity appeared to account for the lower HDL cholesterol levels in Pima male subjects compared with that in Caucasian male subjects, but obesity could not explain the lack of differences between the sexes in HDL levels in the Pimas. Triglyceride levels correlated positively with obesity in the Pimas, but the relationship was not as strong as that reported for Caucasians. The results indicate that there are differences in lipoprotein distributions between Pimas and U.S. Caucasians; the relationship between lipoprotein levels and the incidence of coronary disease in the Pimas must be determined.

Adolescent↗
PubMed1983

Diabetes mellitus in Hopi and Navajo indians. Prevalence of microvascular complications.

In a cross-sectional study of Hopi and Navajo Indians with non-insulin-dependent diabetes mellitus, we found vascular complications to be strongly related to the duration of diabetes. In patients with diabetes of at least 10 yr duration, retinopathy was found in 57%, nephropathy in 40%, peripheral neuropathy in 21%, and peripheral vascular disease in 28%. For the Hopi and Navajo, the duration-specific prevalence rates of microvascular disease were very similar to prevalence rates found in many other populations. Thus we question the concept, based on reports in the late 1960s, that the Hopi and Navajo Indians have hyperglycemia as an isolated chemical abnormality unaccompanied by other manifestations of diabetes mellitus.

Adult↗
PubMed1982

Mortality as a function of obesity and diabetes mellitus.

Mortality according to body mass index (weight/height2) was studied in 2197 Pima Indians aged 15-74 years, as part of the longitudinal study of diabetes begun in 1965 in the Gila River Indian Community of Arizona. The Pima Indians are a population with a high prevalence of obesity, and they have the highest known incidence of type II (non-insulin dependent) diabetes mellitus. Among males, mortality was greatest in those with a body mass index of at least 40 kg/m2, but obesity had little effect on mortality at body mass indices below 40 kg/m2. Age-specific death rates in women were not consistently related to obesity, although mortality in subjects with diabetes was higher than in those without. In men, diabetes had little effect on mortality. In this study, as in several other mortality studies, the lowest mortality rates were experienced by people with body weights well above those recommended as "desirable" by the Society of Actuaries in 1959. Thus, the applicability of the "desirable" weight standards in common use is questioned.

Adolescent↗
PubMed1981

HLA-A2 and type 2 (insulin independent) diabetes mellitus in Pima Indians: an association of allele frequency with age.

In Pima Indians with Type 2 (insulin independent) diabetes mellitus, HLA-A2 allele frequencies were inversely associated with age, (0.72, 0.59, and 0.52 in those less than 35, 35 to 54, and 55 years old and over, respectively). This suggests that there may be a gene closely linked with the HLA-A locus which plays a role in the expression of diabetes in the Pimas by contributing to an earlier age of onset. HLA-A2 was found in 65% non-diabetic and 81% of 191 diabetic subjects (relative risk = 2.2).

Adult↗
PubMed1981

Diabetes incidence in Pima indians: contributions of obesity and parental diabetes.

The incidence of diabetes mellitus was determined in 3137 Pima Indians during periodic examinations that included measurement of weight, height, and glucose tolerance. Incidence was strongly related to preceding obesity, increasing steadily from 0.8 plus or minus 0.8 cases/1000 person-years in subjects with body mass index less than 20 kg/m2 to 72.2 plus or minus 14.5 cases/1000 person-years (rate plus or minus standard error) in those with body mass index greater than or equal to 40 kg/m2, when age-sex adjusted the 1970 US white population. There was little relationship between diabetes prevalence and concurrent obesity, illustrating the importance of longitudinal studies in estimating the effect of obesity on the occurrence of a disease for which weight loss is a manifestation. The association of diabetes incidence with obesity remained within each group when subjects were classified by the diabetic status of their parents, another important risk factor for diabetes. Adjusted for age and obesity, incidence was 2.3 times as high (p = 0.039) in subjects with one diabetic parent and 3.9 times as high (p = 0.0003) in those with two diabetic parents as in those with two nondiabetic parents. In the Pimas, both obesity and diabetes have become more common during this century, perhaps as a result of rapid cultural and dietary changes in a population genetically susceptible to diabetes. Similar increases in obesity and diabetes appear to be occurring in many other parts of the world.

Adolescent↗
PubMed1980

Development of retinopathy and proteinuria in relation to plasma-glucose concentrations in Pima Indians.

The risks of microvascular complications over periods of 3 and 6 years in relation to baseline plasma glucose concentrations were estimated in Pima Indians of Arizona aged 25 years or more and who were not taking hypoglycaemic medicine at their initial examinations. Retinopathy (microaneurysms, haemorrhages, or neovascularisation) developed within 3 years in 1% of 181 subjects with initial fasting plasma glucose concentrations less than 140 mg/dl (1 mg/dl = 0.0555 mmol/l) and in 13% of 39 subjects with higher initial fasting plasma glucose levels. No one with an initial 2 h glucose concentration less than 200 mg/dl had retinopathy within 3 years, but the rate was 12% in 60 subjects with higher glucose concentrations. Retinopathy developed within 6 years in 1% of 446 subjects whose 2 h post-load glucose concentrations were less than 200 mg/dl and in 20% of 113 subjects with higher levels. Subsequent development of heavy proteinuria (urine protein/creatinine ratio at least 1.0) was less common than that of retinopathy, but was similarly related to the initial fasting and 2 h plasma glucose concentrations. The finding that these microvascular complications rarely appeared in individuals with fasting plasma glucose concentrations less than 140 mg/dl or 2 h plasma glucose concentrations less than 200 mg/dl supports the validity of these concentrations as part of the new diagnostic criteria for diabetes mellitus.

Arizona↗
PubMed1980

Increased incidence of retinopathy in diabetics with elevated blood pressure. A six-year follow-up study in Pima Indians.

The incidence of retinopathy was assessed in 188 diabetic and 284 nondiabetic Pima Indian adults six years after an initial examination had shown each to be free of retinopathy. Exminations included direct ophthalmoscopy through dilated pupils. The incidence of retinal lesions was strongly related to the presence of diabetes and, among the diabetic subjects, to insulin treatment, disease duration, plasma glucose concentration, and presence of other complications such as proteinuria, loss of deep tendon reflexes, and increased vibration-sensation threshold. In diabetic subjects not taking insulin, the incidence of exudates in those with systolic blood pressures of at least 145 mm Hg was more than twice that of those with pressures of less than 125 mm Hg. This association persisted when assessed within categories of subjects stratified according to 13 potentially confounding variables, suggesting that control of blood pressure may reduce the incidence of retinal exudates in diabetics not treated with insulin.

Adult↗
PubMed1979

Development of lithogenic bile during puberty in Pima indians.

To determine whether highly saturated bile is a congenital or acquired characteristic of Pima Indians and to elucidate the basis of the rapid postpubertal increase in gallstones in Pimas, we studied the bile of 66 Pimas nine to 21 years of age. Highly saturated bile is not prevalent among Pimas under the age of 13, but bile saturation increases significantly (P less than 0.05) in both sexes during pubertal growth and development. Bile saturation was 15 per cent higher in females than males. Bile acid pools increased with age in the young men, but not in women. Bile cholesterol saturation correlated with obesity (r = 0.41; P less than 0.001) and urinary estrogen excretion (r = 0.44; P less than 0.001). Highly saturated bile may be present for several years before the onset of cholesterol cholelithiasis.

Adolescent↗