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Biomedical subjects

W C Knowler

Publications and source records attributed to W C Knowler.

At least 163 records · Page 9Linked to original sources
PubMed1991

Racial differences in the relation between blood pressure and insulin resistance.

BACKGROUND: Insulin resistance and the concomitant compensatory hyperinsulinemia have been implicated in the pathogenesis of hypertension. However, reports on the relation between insulin and blood pressure are inconsistent. This study was designed to investigate the possibility of racial differences in this relation. METHODS: We studied 116 Pima Indians, 53 whites, and 42 blacks who were normotensive and did not have diabetes; the groups were comparable with respect to mean age (29, 30, and 31 years, respectively) and blood pressure (113/70, 111/68, and 113/68 mm Hg, respectively). Insulin resistance was determined by the euglycemic-hyperinsulinemic clamp technique during low-dose (40 mU per square meter of body-surface area per minute) and high-dose (400 mU per square meter per minute) insulin infusions. RESULTS: The Pima Indians had higher fasting plasma insulin concentrations than the whites or blacks (176, 138, and 122 pmol per liter, respectively; P = 0.002) and lower rates of whole-body glucose disposal during both the low-dose (12.7, 17.1, and 19.5 mmol per minute; P less than 0.001) and the high-dose (38.0, 43.1, and 45.7 mmol per minute; P less than 0.001) insulin infusions. After adjustment for age, sex, body weight, and percentage of body fat, mean blood pressure (calculated as 1/3 systolic pressure + 2/3 diastolic pressure) was significantly correlated with the fasting plasma insulin concentration (r = 0.42) and the rate of glucose disposal during the low-dose (r = -0.41) and high-dose (r = -0.49) insulin infusions (P less than 0.01 for each) in whites, but not in Pima Indians (r = -0.06, -0.02, and -0.04, respectively) or blacks (r = -0.10, -0.04, and 0.02, respectively). CONCLUSIONS: The relations between insulinemia, insulin resistance, and blood pressure differ among racial groups and may be mediated by mechanisms active in whites, but not in Pima Indians or blacks.

Adult↗
PubMed1991

Obesity in the Pima Indians: its magnitude and relationship with diabetes.

Members of the Pima Indian population are obese, on average, as estimated by the body mass index (BMI). Young adults have had the highest BMIs and there have been modest increases in age- and sex-specific mean BMIs for the past 25 y. These observations suggest that the older adults have had less exposure to factors leading to obesity than have the younger adults. Compared with children studied early in this century, present-day Pima children are much heavier for height, suggesting that the degree of obesity has increased since that time. Obesity in the Pimas is familial and has complex relationships with non-insulin-dependent diabetes mellitus, a common disease in this population. Obesity predicts the development of diabetes; once people have diabetes, however, they tend to lose weight. Thus, obesity should not be studied in this population without also considering diabetes, which tends to limit the degree of obesity.

Aged↗
PubMed1991

Studies of the etiology of obesity in Pima Indians.

Studies have been conducted on various metabolic characteristics of lean and obese Pima Indians, including studies of fat-cell morphology, glucose transport, and lipolysis; lipoprotein lipase activities; sodium-potassium ATPase in red cells, adipocytes, and fibroblasts; lipids and lipoprotein metabolism; fatty acid metabolism; and sterol balance. Insulin concentrations, insulin binding, insulin action on glucose disposal, fatty acid metabolism, and islet function were compared in lean and obese individuals, and the relationship between insulin resistance and muscle morphology was explored. To explore potential abnormalities in energy balance, calorie intake and gastric emptying were compared in lean and obese Pimas and measurements of energy expenditure were performed. The data suggest that there are multiple metabolic differences that accompany obesity in Native Americans. A lower metabolic rate was a determinant of future weight gain, and abnormalities in use of free fatty acids and cell insulin action were suggested, which emphasize the need for further studies in these areas.

Adenosine Triphosphatases↗
PubMed1991

Insulin resistance associated with lower rates of weight gain in Pima Indians.

UNLABELLED: Insulin resistance is commonly associated with obesity and noninsulin-dependent diabetes. Whereas it predicts the development of diabetes, its effect on body weight change is unknown. We measured glucose disposal rates at submaximally- and maximally-stimulating insulin concentrations in 192 nondiabetic Pima Indians and followed their weight change over 3.5 +/- 1.8 y (mean +/- SD). RESULTS: (a) Insulin-resistant subjects gained less weight than insulin-sensitive subjects (3.1 vs. 7.6 kg, P less than 0.0001). (b) The percent weight change per year correlated with glucose disposal at submaximally-(r = 0.19, P less than 0.01) and maximally-stimulating (r = 0.34, P less than 0.0001) insulin concentrations independent of sex, age, initial weight, and 24-h energy expenditure; the correlations were stronger for glucose oxidation than for glucose storage. (c) Weight gain was associated with an increase in insulin resistance more than four times that predicted from the cross-sectional data. We conclude that insulin resistance is associated with a reduced risk of weight gain in nondiabetic Pima Indians.

Adolescent↗
PubMed1991

Glomerular function in Pima Indians with noninsulin-dependent diabetes mellitus of recent onset.

Differential solute clearances were used to characterize glomerular function in 20 Pima Indians with noninsulin-dependent diabetes mellitus (NIDDM) of less than 3 yr duration. 28 Pima Indians with normal glucose tolerance served as controls. In the diabetic group, the glomerular filtration rate (GFR, iothalamate clearance) exceeded the control value by 15% (140 +/- 6 vs. 122 +/- 5 ml/min, P less than 0.01). A corresponding 12% increase in renal plasma flow (RPF) was not statistically significant and did not account fully for the observed hyperfiltration, suggesting a concomitant elevation of the ultrafiltration pressure or coefficient. The median albumin excretion ratio in NIDDM exceeded control by almost twofold (10.1 vs. 5.8 mg/g creatinine), a trend which just failed to achieve statistical significance (P = 0.06). Fractional clearances of dextrans of broad size distribution were also elevated in diabetic subjects, significantly so for larger dextrans of between 48 and 60 A radius. A theoretical analysis of dextran transport through a heteroporous membrane revealed glomerular pores in NIDDM to be uniformly shifted towards pores of larger size than in controls. We conclude that an impairment of barrier size selectivity combined with high GFR elevates the filtered protein load in NIDDM of recent onset. We propose that enhanced transglomerular trafficking of protein may predispose to sclerosis of glomeruli in those Pima Indians with NIDDM who ultimately develop diabetic nephropathy.

Adolescent↗
PubMed1991

Abnormal glucose tolerance during pregnancy in Pima Indian women. Long-term effects on offspring.

The long-term effects on offspring of abnormal glucose tolerance detected during pregnancy were examined in 552 Pima Indian offspring 5-24 yr of age. Fasting hyperinsulinemia, presumably reflecting increased insulin resistance, occurred at an earlier age in the offspring of women who had abnormal glucose tolerance during pregnancy, and these offspring were more obese and had higher rates of abnormal glucose tolerance. When confounding factors were controlled, a 1 mM higher 2-h postload glucose concentration during pregnancy resulted in a significantly higher prevalence of diabetes in the offspring (odds ratio = 162). Maternal 2-h glucose concentration during pregnancy was also a significant predictor of glucose concentration during pregnancy in the offspring (P = 0.011). Thus, the metabolic abnormalities associated with the diabetic pregnancy result in long-term effects on the offspring, including insulin resistance, obesity, and diabetes, which in turn may contribute to transmission of risk for developing the same problems in the next generation.

Adolescent↗
PubMed1991

Prevalence of diabetes in Mexican Americans, Cubans, and Puerto Ricans from the Hispanic Health and Nutrition Examination Survey, 1982-1984.

The purpose of this study was to estimate the prevalence of diagnosed and undiagnosed diabetes among Mexican Americans, Cubans, and Puerto Ricans in the United States and compare these estimates to data from prior surveys for U.S. non-Hispanic whites and blacks. Data for this study are from the Hispanic Health and Nutrition Examination Survey, a multipurpose cross-sectional survey of three U.S. Hispanic populations conducted in 1982-1984. The interviewed sample of people aged 20-74 yr included 3935 Mexican Americans in the southwest, 1134 Cubans in Florida, and 1519 Puerto Ricans in the New York City area. The diabetes component consisted of interview questions on diabetes diagnosis and treatment and an oral glucose tolerance test administered to a subsample. The prevalence of diabetes was two to three times greater for Mexican Americans and Puerto Ricans than for non-Hispanic whites surveyed in 1976-1980. In Cubans, the prevalence was similar to that for non-Hispanic whites. In men and women 45-74 yr of age, the prevalence of diabetes was extremely high for both Mexican Americans (23.9%) and Puerto Ricans (26.1%) compared with Cubans (15.8%) or non-Hispanic whites (12%). The total prevalence of diabetes was not significantly different for Mexican Americans and Puerto Ricans but was significantly lower for Cubans. The relatively lower prevalence of diabetes among Cubans and the high prevalence in both Mexican Americans and Puerto Ricans may be related to socioeconomic, genetic, behavioral, or environmental factors.

Adult↗
PubMed1991

Assessment of risk of overt nephropathy in diabetic patients from albumin excretion in untimed urine specimens.

The ability of an albumin-to-creatinine ratio, measured in a single untimed urine specimen, to indicate the likelihood of developing overt diabetic nephropathy was determined in 439 Pima Indians (134 men, 305 women) aged 25 years or older with non-insulin-dependent diabetes. During a mean follow-up period of 4.2 years, 59 (13%) of the subjects developed overt nephropathy, 47 (80%) of whom had albumin-to-creatinine ratios of 30 mg/g or greater at baseline. Subjects with albumin-to-creatinine ratios of 30 to 299 mg/g (a level of excretion often termed "microalbuminuria") had 9.2 times (95% confidence interval, 4.4 to 21.4) the incidence of overt nephropathy of those with ratios of less than 30 mg/g. Furthermore, the albumin-to-creatinine ratio remained a strong predictor of overt nephropathy even when controlled for age, sex, diabetes duration, mean blood pressure, and 2-hour postload plasma glucose concentration with a proportional-hazards function analysis. Thus, an albumin-to-creatinine ratio measured in a single untimed urine specimen is an effective means of identifying diabetic subjects who are at risk of developing overt nephropathy that could replace the more traditional timed urine collections.

Adult↗
PubMed1991

A two-step model for development of non-insulin-dependent diabetes.

Both insulin resistance and beta-cell dysfunction occur during the development of non-insulin-dependent diabetes mellitus (NIDDM), but controversy exists about which lesion is primary. Based on longitudinal studies in the Pima Indians, a population with the world's highest reported prevalence of NIDDM, a two-step model for development of the disease is proposed. The first step is transition from normal to impaired glucose tolerance, for which insulin resistance is the main determinant, and the second and later step is worsening from impaired glucose tolerance to diabetes, in which beta-cell dysfunction plays a critical role. This hypothesis is consistent with findings from other ethnic groups from many parts of the world.

Adolescent↗
PubMed1990

Islet amyloid polypeptide in diabetic and non-diabetic Pima Indians.

Islet amyloid may have a pathological role in the development of Type 2 (non-insulin-dependent) diabetes mellitus. The prevalence of islet amyloid has been investigated on post-mortem pancreatic tissue from both diabetic and non-diabetic Pima Indian subjects who had previously been assessed by oral glucose tolerance tests. Islets were examined for amyloid deposits and for cellular immunoreactivity to pancreatic hormones and islet amyloid polypeptide, the constituent peptide of islet amyloid. Twenty of 26 diabetic subjects (77%) had islet amyloid, compared with one of 14 non-diabetic subjects (7%). Twelve of the diabetic subjects (46%) had amyloid in more than 10% of their islets, whereas only 4% of islets were affected in a single non-diabetic subject. Positive immunoreactivity for islet amyloid peptide was present in the islet amyloid and in islet cells in 54% of the diabetic and 50% of the non-diabetic subjects. Islet amyloid in diabetic Pima Indians may indicate a primary Beta-cell defect which interacts with insulin resistance to produce diabetes, or may develop as a result of Beta-cell dysfunction induced by insulin resistance and hyperglycaemia.

Aged↗
PubMed1990

Familial predisposition to renal disease in two generations of Pima Indians with type 2 (non-insulin-dependent) diabetes mellitus.

We studied the occurrence of renal disease by measuring serum creatinine and urine protein concentrations in the diabetic members of 316 Pima Indian families with Type 2 (non-insulin-dependent) diabetes in two successive generations to determine if diabetic renal disease aggregates in families. After adjustment for sex and other risk factors, proteinuria occurred among 14.3% of the diabetic offspring if neither parent had proteinuria, 22.9% if at least one diabetic parent had proteinuria, and 45.9% if both parents had diabetes and proteinuria. Among male offspring, an elevated serum creatinine concentration (greater than or equal to 177 mumol/l) was present in 11.7% if the parent had an elevated creatinine and in 1.5% if the parent did not. Thus, proteinuria and high serum creatinine aggregated in diabetic families, suggesting that susceptibility to renal disease is inherited independently of diabetes.

Adult↗
PubMed1990

Risk factors for gallstone disease in the Hispanic populations of the United States.

The 1982-1984 Hispanic Health and Nutrition Examination Survey used ultrasonography to investigate risk factors for gallstone disease (gallstones or cholecystectomy). Mexican American, Cuban American, and Puerto Rican men (n = 968) and women (n = 1,325) aged 20-74 years were selected from household samples in nine states. Among men, the risk of gallstone disease increased with age, education, and subscapular skinfold thickness. Among women, the risk of gallstone disease increased with age, body mass index, four skinfold measures, diabetes, impaired glucose tolerance, and oral contraceptive usage, but not with parity. Women currently using oral contraceptives were also found to be at increased risk of current gallstones. Menopause was a risk factor for gallstone disease and cholecystectomy. Alcohol consumption was negatively related to the risk of gallstone disease. In men, the cholesterol/high density lipoprotein cholesterol ratio was positively related to gallstone disease and, in women, this ratio was negatively related. This interaction between the effect of sex and the cholesterol/high density lipoprotein cholesterol ratio on gallstone disease was highly significant (p = 0.002). Mexican Americans were at increased risk of gallstone disease even when other risk factors were controlled in multiple logistic regression analysis.

Adult↗
PubMed1990

Low ratio of fat to carbohydrate oxidation as predictor of weight gain: study of 24-h RQ.

Reduced oxidation of fat leading to a positive fat balance could be a factor in the development of obesity. Twenty-four-hour respiratory quotient (RQ) was measured in 152 nondiabetic Pima Indians fed a weight-maintenance diet [87 males and 65 females; 27 +/- 6 yr (mean +/- SD); 93.9 +/- 22.9 kg; 32 +/- 9% fat]. Twenty-four-hour RQ varied from 0.799 to 0.903. Prior change in body weight, 24-h energy balance, sex, and percent body fat explained 18% of the variance in 24-h RQ (P less than 0.001). In a subgroup of 66 siblings from 28 families, family membership explained 28% of the remaining variance in 24-h RQ (P less than 0.05). In 111 subjects for whom follow-up data (25 +/- 11 mo) were available, 24-h RQ was correlated with subsequent changes in body weight and fat mass (r = 0.27, P less than 0.01 and r = 0.19, P less than 0.05, respectively). Subjects with higher 24-h RQ (90th percentile) independent of 24-h energy expenditure were at 2.5 times higher risk of gaining greater than or equal to 5 kg body weight than those with lower 24-h RQ (10th percentile). We conclude that in Pima Indians fed a standard diet 1) family membership is the principal determinant of the ratio of fat to carbohydrate oxidation, and 2) a low ratio of fat to carbohydrate oxidation is associated with subsequent weight gain independent of low energy expenditure and may contribute to the familial aggregation of obesity.

Adult↗
PubMed1990

Low incidence of fatal coronary heart disease in Pima Indians despite high prevalence of non-insulin-dependent diabetes.

The incidence of fatal coronary heart disease (CHD) was determined in a population of Pima Indians from the Gila River Indian Community in Arizona. Between 1975 and 1984, 394 deaths occurred among 4,828 subjects aged 5 years or older, and 199 of these occurred in the 1,093 persons with non-insulin-dependent diabetes. Only 28 deaths were attributed to CHD; all occurred among the 689 diabetic persons 45 years of age or older. No CHD deaths occurred among the 419 nondiabetic subjects 45 years of age or older. The rate of fatal CHD among the diabetic subjects was higher in men than in women and increased with advancing age and duration of diabetes. A higher incidence of fatal CHD was associated with proteinuria, renal insufficiency, medial arterial calcification, diabetic retinopathy, insulin therapy, and an abnormal electrocardiogram. In Pima Indians aged 50-79 years, the incidence of fatal CHD was less than half that found in the Framingham population after controlling for age, sex, and diabetes (incidence rate ratio, 0.4; 95% confidence interval, 0.2-0.7). Factors protecting Pima Indians from fatal CHD may include racial heritage, low serum concentrations of total and low density lipoprotein cholesterol, and rarity of heavy smoking. Among the diabetic subjects, mortality from diabetic renal disease, which shows many of the same risk factors, may selectively compete and remove those at risk for fatal CHD. This would not, however, explain the lack of fatal CHD among the nondiabetic subjects. Fatal CHD shares many of the risk factors associated with the specific microvascular complications of diabetes, and diabetes and its associated attributes are the major predictors of fatal CHD in this population.

Aged↗
PubMed1990

Disproportionately elevated proinsulin in Pima Indians with noninsulin-dependent diabetes mellitus.

Fasting serum total immunoreactive insulin (IRI), true insulin, and true proinsulin (PI) were measured in 169 Pima Indians. The relationship of these variables to glucose tolerance, obesity, and parental diabetes was studied. Seventy-seven subjects had normal glucose tolerance, 46 had impaired glucose tolerance (IGT), and 46 had noninsulin-dependent diabetes mellitus (NIDDM) by WHO criteria. In subjects with normal glucose tolerance, the geometric mean ratio of PI to IRI (PI/IRI) was 10.8% (arithmetic mean, 12.5%), similar to that reported in other ethnic groups with lower prevalence rates of NIDDM. Parental diabetes had no effect on PI/IRI. Obese persons (body mass index, greater than or equal to 27 kg/m2) with normal glucose tolerance had PI/IRI of 9.3% compared with 16.3% for the nonobese (P less than 0.001), and PI/IRI was negatively correlated with body mass index (r = -0.34; P = 0.002). Proinsulin was disproportionately elevated in NIDDM (geometric mean PI/IRI, 19.9%; arithmetic mean, 23.6%), and the degree of elevation was related to the severity of hyperglycemia, but not the duration of diabetes. Subjects with IGT were more obese and had higher fasting plasma glucose (5.7 vs. 5.2 mmol/L; P = 0.025), true insulin (250 vs. 125 pmol/L; P less than 0.001), and PI concentrations (26 vs. 15 pmol/L; P less than 0.001) than those with normal glucose tolerance but similar mean PI/IRI (9.4 vs. 10.8%; P = 0.4). These findings indicate that Pima Indians with NIDDM have a disproportionate elevation of PI consistent with the hypothesis that beta-cell dysfunction associated with hyperglycemia leads to the release of proinsulin-rich immature granules.

Adolescent↗
PubMed1990

Type 2 diabetes mellitus and periodontal disease.

The relationship between type 2 diabetes mellitus and periodontal disease was evaluated in 2,878 Pima Indians of the southwestern United States. Two independent measures of periodontal disease, probing attachment loss and radiographic bone loss, were used to compare prevalence and severity of periodontal disease in diabetic and nondiabetic subjects. In all age groups studied, subjects with diabetes had a higher prevalence of periodontal disease, indicating that diabetes may be a risk factor for periodontal disease.

Adolescent↗
PubMed1990

Development of questionnaire to examine relationship of physical activity and diabetes in Pima Indians.

There was a need to design a questionnaire that could accurately assess the activity patterns of Native Americans to evaluate the relationship between physical activity and diabetes. Such a questionnaire was developed and implemented into the data collection scheme of the prospective Pima Indian Study of Arizona. The questionnaire, which assesses historical, past-year, and past-week leisure and occupational activity, was examined in 29 Pima individuals aged 21-36 yr and was shown to be reliable with test-retest correlations (rank-order correlations ranged from 0.62 to 0.96 for leisure and occupational activity). Reproducibility of the past-year leisure physical-activity estimate was determined in 69 participants aged 10-59 yr and was found to be reliable in all age-groups with the exception of the 10- to 14-yr-old age-group (rank-order correlations were 0.31 in the 10- to 14-yr-old age-group compared to 0.88 to 0.92 in those greater than 20 yr of age). Validity of the current-activity section of the questionnaire was demonstrated indirectly through comparisons with activity monitors. The past-week leisure-activity estimate was related to the Caltrac activity monitor counts per hour (rho = 0.62, P less than 0.05, n = 17). In summary, a physical-activity questionnaire has been developed that is both reliable and feasible to use in the Pima Indian population to evaluate the relationship of physical activity to non-insulin-dependent diabetes mellitus.

Adolescent↗