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Biomedical subjects

W G Abbott

Publications and source records attributed to W G Abbott.

17 recordsLinked to original sources
PubMed1992

Increased receptor binding of low-density lipoprotein from individuals consuming a high-carbohydrate, low-saturated-fat diet.

The substitution of saturated fat by complex carbohydrate, according to current dietary recommendations, results in a decrease of plasma and low-density lipoprotein (LDL) cholesterol levels. To determine whether this decrease might result from structural and thus functional changes in LDL particles, the binding internalization and degradation of 125I-LDL were measured using TR715-19 cells, a mutant CHO line into which has been transfected the human LDL receptor, and in which measurements of binding are highly reproducible. Eleven nondiabetic subjects (35 +/- 4 years, 27% +/- 3% body fat) were studied after they had 15% protein, and 560 mg cholesterol/d and the other containing 21% fat (6% saturated), 65% carbohydrate, 14% protein, and 524 mg cholesterol/d.LDL cholesterol levels decreased form 125 +/- 6 to 108 +/- 5 mg/dl (P < .01) on the high-carbohydrate diet. There was an increase in the binding affinity of LDL (Kd 6.6 +/- 2.6 v 7.3 +/- 2.7 micrograms/mL +/- SD; P < .02), and internalization (P < .10), and degradation (P < .05) were also higher. The data suggest that decreasing dietary saturated fat may cause alterations in LDL composition that result in increased receptor clearance; this may partially explain the LDL-decreasing effect of this dietary change.

Adult↗
PubMed1992

T cell receptor alpha-chain polymorphic allele frequencies in Caucasians and Polynesians.

Restriction length polymorphisms in the variable and constant regions of the T cell receptor alpha-chain were examined in 42 Caucasians, 29 Maoris and 27 Pacific Islanders. Southern blots of Taq I digested DNA were hybridized with the T cell receptor alpha-chain probe pY14. Our results confirm that a 1.4 kb T cell receptor alpha chain-Taq 1 band is allelic to a 0.5 kb band. A significant difference in the frequency of the 1.4 and 0.5 kb alleles of the variable region of the alpha-chain was detected in Caucasians when compared with Maoris or Pacific Islanders (P < 0.0001). No differences in the frequency of the 2.0 and 7.0 kb alleles of the constant region gene were detected between any of the racial groups. These data may be relevant to ethnic differences in susceptibility to immune disorders.

Adult↗
PubMed1991

Evaluation of metabolic effects of substitution of complex carbohydrates for saturated fat in individuals with obesity and NIDDM.

Dietary recommendations for diabetic patients now generally include the reduction of total and saturated fat and an increase in complex carbohydrates. We conducted two series of studies on individuals with obesity and/or non-insulin-dependent diabetes mellitus (NIDDM) to assess the effects of this dietary recommendation on both lipoproteins and their metabolism as well as on insulin secretion and action and energy expenditure. Both series compared a diet high in saturated fat with a diet high in complex carbohydrates and fiber. Calories and proportion of protein were constant. In the first set of studies, we sought to examine the effect of replacement of saturated fat with complex carbohydrate in a regimen with conventional foods that would closely approximate foods expected to be used and recommended to diabetic patients. In the second regimen, we examined a more extreme difference between carbohydrate content and fat content using a dietary change that would approximate the contrasts between traditional diets of Native Americans or other cultures and a modern westernized diet. The effects on lipoproteins included consistent decreases in total and low-density lipoprotein (LDL) cholesterol (av 10%), minimum to no change in high-density lipoprotein cholesterol, and insignificant changes in total or very-low-density lipoprotein (VLDL) triglycerides or 24-h triglyceride profiles. Changes in total and LDL cholesterol required 3-4 wk to reach equilibrium. Metabolic studies used to elucidate the reasons for the decrease in LDL cholesterol confirmed no stimulation of VLDL triglyceride or apolipoprotein B (apoB) production on the high-carbohydrate diet. The decrease in LDL appeared to be due to decreases in mechanisms that convert VLDL to LDL and increased activity of LDL apoB clearance. There were no changes in fasting and 2- or 24-h glucose profiles or in fasting and 2-h insulin concentrations in individuals consuming a diet of 30% fat and 55% carbohydrate. However, in the study with traditional foods, where dietary carbohydrate was 70% and fat only 15%, there was an improvement in glucose tolerance. It was accompanied by an improvement in glucose-mediated glucose disposal and insulin secretion. Finally, with a whole-body calorimeter, we found no difference between the high-fat and high-carbohydrate diets in terms of 24-h energy expenditure. In individuals having a wide range of obesity and glucose tolerance, substitution of complex carbohydrates for saturated fat has beneficial effects of lowering LDL cholesterol and possibly improving glucose tolerance and insulin secretion but without having any adverse effects on lipoprotein metabolism or energy expenditure.

Body Weight↗
PubMed1990

Energy expenditure in humans: effects of dietary fat and carbohydrate.

A high-dietary fat intake may be an important environmental factor leading to obesity in some people. The mechanism could be either a decrease in energy expenditure and/or an increase in caloric intake. To determine the relative importance of these mechanisms we measured 24-h energy expenditure in a whole body calorimeter in 14 nondiabetic subjects and in six subjects with non-insulin-dependent diabetes mellitus, eating isocaloric, weight-maintenance, high-fat, and high-carbohydrate diets. All subjects were Pima Indians. In nondiabetics, the mean total 24-h energy expenditure was similar (2,436 +/- 103 vs. 2,359 +/- 82 kcal/day) on high-fat and high-carbohydrate diets, respectively. The means for sleeping and resting metabolic rates, thermic effect of food, and spontaneous physical activity were unchanged. Similar results were obtained in the diabetic subjects. In summary, using a whole body calorimeter, we found no evidence of a decrease in 24-h energy expenditure on a high-fat diet compared with a high-carbohydrate diet.

Adult↗
PubMed1990

Effect of a high-carbohydrate, low-saturated-fat diet on apolipoprotein B and triglyceride metabolism in Pima Indians.

The mechanisms by which high-carbohydrate, low-saturated-fat diets lower LDL cholesterol (LDLC) concentrations are unknown. In this study, kinetics of VLDL, intermediate density lipoprotein (IDL), and LDL apoprotein B and VLDL triglyceride were determined in seven nondiabetic (ND) and seven non-insulin-dependent diabetic (NIDDM) Pima Indian subjects on high-fat and high-carbohydrate (HICHO) diets. Metabolic changes were similar in ND and NIDDM. On the HICHO diet, LDLC decreased (131 +/- 8 vs. 110 +/- 7 mg/dl, P less than 0.0001) in all subjects. Mean fasting and 24-h triglyceride (TG) concentrations were unchanged, as were mean production rates and fractional clearance rates (FCR) of VLDL apoB and VLDL TG. The mean VLDL apoB pool size (303 +/- 20 vs. 371 +/- 38 mg, P = 0.01) increased owing to a decrease in the mean transport rate (10.7 +/- 1.1 vs. 8.4 +/- 0.9 mg/kg fat-free mass (ffm) per day, P less than 0.0001) and the mean rate constant (2.3 +/- 0.2 vs. 1.5 +/- 0.2, P less than 0.001) for the VLDL apoB to IDL apoB conversion pathway. The mean transport rate of VLDL apoB to LDL apoB via IDL (10.2 +/- 0.9 vs. 8.0 +/- 0.8 mg/kg ffm per day, P less than 0.001) decreased. Mean LDL apoB concentrations decreased (70 +/- 5 vs. 61 +/- 5 mg/dl, P less than 0.001) on the HICHO diet. Means for total LDL apoB transport rate, LDL apoB FCR, and LDLC/apoB ratios were unchanged. In summary, the HICHO diet decreased the activity of mechanisms that convert VLDL to LDL, which contributed to the decrease in LDLC in all subjects. There was also evidence in some subjects for increased activity of LDL apoB clearance mechanisms, and a decrease in the LDLC to apoB ratio.

Apolipoproteins B↗
PubMed1989

Effects of replacing saturated fat with complex carbohydrate in diets of subjects with NIDDM.

This study examined the safety of an isocaloric high-complex carbohydrate low-saturated fat diet (HICARB) in obese patients with non-insulin-dependent diabetes mellitus (NIDDM). Although hypocaloric diets should be recommended to these patients, many find compliance with this diet difficult; therefore, the safety of an isocaloric increase in dietary carbohydrate needs assessment. Lipoprotein cholesterol and triglyceride (TG, mg/dl) concentrations in isocaloric high-fat and HICARB diets were compared in 7 NIDDM subjects (fat 32 +/- 3%, fasting glucose 190 +/- 38 mg/dl) and 6 nondiabetic subjects (fat 33 +/- 5%). They ate a high-fat diet (43% carbohydrate; 42% fat, polyunsaturated to saturated 0.3; fiber 9 g/1000 kcal; cholesterol 550 mg/day) for 7-10 days. Control subjects (3 NIDDM, 3 nondiabetic) continued this diet for 5 wk. The 13 subjects changed to a HICARB diet (65% carbohydrate; 21% fat, polyunsaturated to saturated 1.2; fiber 18 g/1000 kcal; cholesterol 550 mg/day) for 5 wk. NIDDM subjects on the HICARB diet had decreased low-density lipoprotein cholesterol (LDL-chol) concentrations (107 vs. 82, P less than .001), but their high-density lipoprotein cholesterol (HDL-chol) concentrations, glucose, and body weight were unchanged. Changes in total plasma TG concentrations in NIDDM subjects were heterogeneous. Concentrations were either unchanged or had decreased in 5 and increased in 2 NIDDM subjects. Nondiabetic subjects on the HICARB diet had decreased LDL-chol (111 vs. 81, P less than .01) and unchanged HDL-chol and plasma TG concentrations).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Reduced rate of energy expenditure as a risk factor for body-weight gain.

The contribution of reduced energy expenditure to the development of obesity has been a point of controversy. We measured 24-hour energy expenditure (adjusted for body composition, age, and sex), in a respiratory chamber, in 95 southwestern American Indians. Energy expenditure correlated with the rate of change in body weight over a two-year follow-up period (r = -0.39, P less than 0.001). The estimated risk of gaining more than 7.5 kg in body weight was increased fourfold in persons with a low adjusted 24-hour energy expenditure (200 kcal per day below predicted values) as compared with persons with a high 24-hour energy expenditure (200 kcal per day above predicted values; P less than 0.01). In another 126 subjects, the adjusted metabolic rate at rest at the initial visit was also found to predict the gain in body weight over a four-year follow-up period. When the 15 subjects who gained more than 10 kg were compared with the remaining 111 subjects, the initial mean (+/- SD) adjusted metabolic rate at rest was lower in those who gained weight (1694 +/- 103 vs. 1764 +/- 109 kcal per day; P less than 0.02) and increased to 1813 +/- 134 kcal per day (P less than 0.01) after a mean weight gain of 15.7 +/- 5.7 kg. In a group of 94 siblings from 36 families, values for adjusted 24-hour energy expenditure aggregated in families (intraclass correlation = 0.48). We conclude that a low rate of energy expenditure may contribute to the aggregation of obesity in families.

Adolescent↗
PubMed1988

Short-term energy balance: relationship with protein, carbohydrate, and fat balances.

Energy balance (energy intake-energy expenditure) is known to vary considerably on a day-to-day basis in free-living individuals. The extent to which stores of protein, carbohydrate, and fat are used to store short-term surpluses of energy and the extent to which these stores are used to make up temporary energy deficits are incompletely known. We have measured body energy balance as well as carbohydrate, fat, and protein balances in 27 Caucasian men and 27 Caucasian women over a 24-h period in a respiratory chamber. An estimated weight-maintenance diet was fed to each subject. Because of individual differences in family background, body composition, activity, and the failure of some subjects to eat all of their food, these estimates are not exact, and energy balance is rarely achieved. Energy balance was correlated with fat balance in men (r = 0.79, P less than 0.0001) and women (r = 0.72, P less than 0.0001), and the slope of this relationship was not distinguishable from unity in men (1.16 +/- 0.18) or women (0.80 +/- 0.15). There were no correlations between energy balance and either carbohydrate or protein balances. This study demonstrates that carbohydrate and protein stores are closely regulated by adjusting oxidation to intake. Thus fat, rather than carbohydrate or protein, is almost exclusively used or stored in response to day-to-day fluctuations in energy balance.

Adult↗
PubMed1987

Coordination of very low-density lipoprotein triglyceride and apolipoprotein B metabolism in humans: effects of obesity and non-insulin-dependent diabetes mellitus.

To understand the relationship between very low-density lipoprotein (VLDL) triglyceride and VLDL apolipoprotein (apo) B, we studied their metabolisms simultaneously in 53 subjects with a range of obesity and glycemia. Obese subjects had increased production of both VLDL apo B and VLDL triglyceride and more VLDL of normal composition. Compared with nondiabetics, diabetic subjects had decreased clearance of both VLDL apo B and VLDL triglyceride, increased production of VLDL triglyceride but not of VLDL apo B, and more VLDL of abnormal composition. Production of both VLDL apo B and VLDL triglyceride were significantly correlated with plasma insulin concentrations, and rates of clearance of both were inversely correlated with plasma glucose. There was no direct correlation between total plasma free fatty acid concentration and production of either VLDL triglyceride or VLDL apo B, but VLDL triglyceride production was found to account for only a very small proportion of the nonoxidative component of free fatty acid turnover. We suggest that in obese subjects hyperinsulinemia induces overproduction of both VLDL apo B and VLDL triglyceride. In diabetes VLDL is increased in part because of decreased clearance; the altered composition is the result of the increase in VLDL-triglyceride production independent of apo B. The increase in VLDL triglyceride production may be mediated through plasma free fatty acids or glucose, although assessment of the relationship between these precursors and VLDL triglyceride is confounded by the fact that only a small portion of free fatty acids or glucose is converted to VLDL triglyceride.

Adult↗
PubMed1987

Integrated study of low density lipoprotein metabolism and very low density lipoprotein metabolism in non-insulin-dependent diabetes.

The metabolisms of VLDL, IDL, and LDL and their interconversions have been studied in ten obese untreated male Pima Indian diabetics compared to 16 age-, sex-, and weight-matched nondiabetics. VLDL was elevated in the diabetics and had abnormal composition, as indicated by a significantly higher ratio of triglyceride/apo B. Fractional catabolic rates for both VLDL apoB and VLDL triglyceride were lower in diabetics, and diabetics had increased production of VLDL triglyceride but not VLDL apoB compared to obese nondiabetics. A higher proportion of VLDL apoB was removed without conversion to LDL in diabetics. LDL cholesterol and apoB were higher in diabetics, but production of LDL apoB was not different from nondiabetics. Fractional catabolic rate for LDL apoB, however, was significantly lower in the diabetics. The data indicate that the triglyceride-rich VLDL in non-insulin-dependent diabetics are less readily converted to LDL, whereas the elevated LDL in this group of diabetics is due to impaired clearance. Thus, decreased conversion of VLDL to LDL and impaired LDL clearance are two opposing phenomena which may influence the LDL concentration of diabetics in either direction. Thus, despite minimal changes in LDL concentration, there are multiple defects in the metabolism of LDL in non-insulin dependent diabetes which may contribute to the increased atherogenesis in this disorder.

Adolescent↗
PubMed1987

Comparison of body composition, adipocyte size, and glucose and insulin concentrations in Pima Indian and Caucasian children.

Pima Indian adults with normal glucose tolerance have higher plasma glucose and insulin concentrations than Caucasian adults. To estimate the age of onset of these differences, and to assess their relationship to abdominal and gluteal adipocyte size, we measured adiposity, adipocyte size, and glucose and insulin concentrations during a glucose tolerance test in lean (less than 20% body fat), prepubertal children from each race. The Pima (n = 13) and Caucasian (n = 10) groups were of similar age, percent body fat, and weight. Pima Indian children had higher fasting glucose (101 +/- 2 v 94 +/- 2 mg/dL, P = .01) and insulin (22 +/- 2 v 15 +/- 2 microU/mL, P less than .01) concentrations and larger abdominal adipocytes (0.49 +/- 0.03 v 0.37 +/- 0.04 microgram lipid/cell, P less than .05) than the Caucasian children. Postprandial glucose and insulin concentrations and gluteal adipocyte size were similar in the two races. The higher plasma glucose and insulin concentrations found in Pima adults are present in lean Pima children, and are associated with increased abdominal adipocyte size. These increases may precede the development of obesity in this racial group.

Adipose Tissue↗
PubMed1987

Skeletal muscle capillary density and fiber type are possible determinants of in vivo insulin resistance in man.

We have compared the capillary density and muscle fiber type of musculus vastus lateralis with in vivo insulin action determined by the euglycemic clamp (M value) in 23 Caucasians and 41 Pima Indian nondiabetic men. M value was significantly correlated with capillary density (r = 0.63; P less than or equal to 0.0001), percent type I fibers (r = 0.29; P less than 0.02), and percent type 2B fibers (r = -0.38; P less than 0.003). Fasting plasma glucose and insulin concentrations were significantly negatively correlated with capillary density (r = -0.46, P less than or equal to 0.0001; r = -0.47, P less than or equal to 0.0001, respectively). Waist circumference/thigh circumference ratio was correlated with percent type 1 fibers (r = -0.39; P less than 0.002). These results suggest that diffusion distance from capillary to muscle cells or some associated biochemical change, and fiber type, could play a role in determining in vivo insulin action. The association of muscle fiber type with body fat distribution may indicate that central obesity is only one aspect of a more generalized metabolic syndrome. The data may provide at least a partial explanation for the insulin resistance associated with obesity and for the altered kinetics of insulin action in the obese.

Adipose Tissue↗
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

Relationships between plasma lipoprotein concentrations and insulin action in an obese hyperinsulinemic population.

Relationships have been observed between lipoprotein concentrations and insulin action. These relationships may be important in explaining the association of insulin resistance and abnormalities of lipoprotein metabolism found in obesity, diabetes, and hypertriglyceridemia. We have measured plasma lipoprotein concentrations and indices of insulin action in 85 men and 56 women, all of whom were normolipidemic and had normal glucose tolerance. The subjects were obese Southwestern American Indians (body mass index 34 +/- 1). Insulin action was measured via the hyperinsulinemic clamp with simultaneous indirect calorimetry. Triglyceride concentrations were inversely related to rates of total insulin-mediated glucose disposal (in men and women, respectively, r = -.37, P less than .01; r = -.24, P less than .10), glucose storage (r = -.31, P less than .01; r = -.25, P less than .10), increase in glucose oxidation (r = -.29, P less than .01; r = -.24, P less than .10), and, in men only, suppression of endogenous glucose production (r = -.32, P less than .01). High-density lipoprotein (HDL) cholesterol concentration was positively related to rates of total insulin-mediated glucose disposal (r = .35, P less than .01; r = .33, P less than .05), increase in carbohydrate oxidation (r = .40, P less than .001; r = .39, P less than .001), suppression of endogenous glucose production (r = .24, P less than .05; r = .29, P less than .05), and, in men only, glucose storage (r = .35, P less than .001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1986

Glucose storage is a major determinant of in vivo "insulin resistance" in subjects with normal glucose tolerance.

In vivo "resistance" to the action of insulin on glucose uptake is commonly found in obesity and is characteristic of noninsulin-dependent diabetes mellitus in obese subjects. To investigate the relationship among glucose uptake, glucose oxidation, and nonoxidative glucose disposal (storage) in subjects with normal glucose tolerance, we studied 25 caucasians and 79 southwestern American Indians, including lean and obese subjects in both groups. The euglycemic clamp technique with simultaneous indirect calorimetry was used to determine rates of glucose uptake and glucose oxidation. These studies were performed at two rates of insulin infusion (40 and 400 mU/m2 X min), with resulting mean plasma insulin concentrations of 113 and 1839 microU/ml, respectively. At the lower insulin infusion rate, there was no glucose storage in subjects with a glucose uptake rate of about 2.2 mg/kg fat free mass X min. In contrast, glucose storage accounted for over 45% of the glucose disposal in subjects with glucose uptake rates over 7.0 mg/kg fat free mass X min studied at similar insulin concentrations. At the high insulin infusion rate, over 70% of the difference in glucose uptake between subjects with a low or high capacity for glucose disposal was due to glucose storage. These studies demonstrated that in normal subjects at both physiological and maximally stimulating plasma insulin concentrations, glucose storage is a major factor in distinguishing between those with low or high rates of insulin-mediated glucose disposal. Since glucose storage may be a specifically activated process, we hypothesize that failure to activate glucose storage is a major defect causing in vivo insulin resistance in subjects with normal glucose tolerance.

Adult↗
PubMed1986

Body composition, adipocyte size, free fatty acid concentration, and glucose tolerance in children of diabetic pregnancies.

Previous studies show that children of women who are diabetic during pregnancy are more obese and have a higher prevalence of non-insulin-dependent diabetes mellitus (NIDDM) than children of women who first developed NIDDM greater than 1 yr after the pregnancy (prediabetic mothers) and children of women who have never developed diabetes (nondiabetic mothers). To determine whether lean and obese children of glucose-intolerant pregnancies can be distinguished from similar children of glucose-tolerant pregnancies, we measured body composition, abdominal and gluteal adipocyte size, fasting free fatty acid (FFA), and fasting and stimulated glucose and insulin concentrations during an oral glucose tolerance test in prepubertal children of glucose-intolerant and prediabetic mothers. Each group ranged in adipocity from 6 to 40% body fat. Age, weight, height, and percentage of body fat were similar in the two groups. There were no significant differences in adipocyte size or in glucose, FFA, C-peptide, and insulin concentrations between the groups. The correlation between abdominal adipocyte size and fasting insulin concentration (r = .91 and .18, t = 2.8, P = .01) was stronger in children from glucose-intolerant than from glucose-tolerant pregnancies, respectively. In terms of the parameters we measured, there are no major differences between children of glucose-intolerant and glucose-tolerant pregnancies.

Adipose Tissue↗