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Biomedical subjects

S Lillioja

Publications and source records attributed to S Lillioja.

At least 55 records · Page 3Linked to original sources
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↗
PubMed1988

Increased rate of Cori cycle in obese subjects with NIDDM and effect of weight reduction.

To determine the contribution of the rate of glucose recycling via the Cori cycle (glucose----3-carbon compounds----glucose) to the higher rate of endogenous glucose production (EGPR) in subjects with non-insulin-dependent diabetes mellitus (NIDDM), we studied eight obese, weight-stabilized diabetic Pima Indians before [93.1 +/- 5.4 kg, 38 +/- 2% body fat, fasting plasma glucose (FPG) 254 +/- 11 mg/dl] and after (87.7 +/- 4.7 kg, 36 +/- 2% body fat, FPG 153 +/- 17 mg/dl) a 5-wk weight-loss diet and eight obese Indians (95.0 +/- 4.2 kg, 36 +/- 2% body fat, FPG 97 +/- 1 mg/dl) with normal glucose tolerance. EGPR and glucose recycling rate were measured during a 4-h primed continuous tracer infusion of [1-13C]glucose, and the rate of reincorporation of 1-13C of glucose into C2-6 positions in glucose was quantified by gas chromatography mass spectrometry. Substrate utilization rates were measured by simultaneous indirect calorimetry. EGPR (corrected for measured rate of recycling) decreased in the diabetic subjects from 3.80 to 2.74 mg.min-1.kg-1 fat-free mass (FFM) (P less than .01) after weight loss, approaching the rate observed in nondiabetic subjects (2.09 mg.min-1.kg-1 FFM).(ABSTRACT TRUNCATED AT 250 WORDS)

Body Composition↗
PubMed1988

Insulin resistance in Pima Indians. A combined effect of genetic predisposition and obesity-related skeletal muscle cell hypertrophy.

Obesity and diabetes are epidemic in the Pima Indians of Southwest United States. Recent evidence suggests that a reduced metabolic rate may predispose the obesity and, since metabolic rate appears to be familial, this may predispose to the familial dependence of obesity. Obesity is associated with an increased risk of diabetes. Insulin resistance is associated with obesity, but is also familial, independent of obesity. In this population insulin resistance is a risk factor for the development of diabetes. Diabetes occurs when insulin secretory failure is superimposed on insulin resistance. Reduced glucose storage in muscle, regulated by glycogen synthase, is important in determining insulin resistance especially at high plasma insulin concentrations and it is possible that a specific genetic defect may be the cause of this. Obesity has its major effect on insulin action at lower plasma insulin concentrations and we propose that this may in part be due to abnormalities of insulin action induced by an increased fat-free mass with a consequent enlargement of muscle cells, a reduced capillary supply, and reduced penetration of insulin into muscle in obese subjects. We propose therefore that insulin resistance may be due to a combination of a genetic defect and obesity-induced changes in the biophysical properties of skeletal muscle. These defects, by slightly increasing the plasma glucose concentration and inducing pancreatic glucose insensitivity, may in turn lead to the development of non-insulin-dependent diabetes mellitus.

Biomechanical Phenomena↗
PubMed1987

Dissociation of in vitro sensitivities of glucose transport and antilipolysis to insulin in NIDDM.

It is unclear from previous studies whether qualitative or only quantitative differences exist in insulin action in adipocytes obtained from obese subjects with non-insulin-dependent diabetes mellitus (NIDDM) when compared with equally obese nondiabetic subjects. In addition, the role of changes in insulin binding as a cause of insulin resistance in NIDDM is still controversial. We compared the sensitivities of glucose transport and antilipolysis to insulin and measured insulin binding in abdominal adipocytes obtained from 45 obese nondiabetic (% fat, 41 +/- 1), 25 obese diabetic (% fat, 40 +/- 1), and 15 nonobese (% fat, 30 +/- 1) female southwestern American Indians. Compared with the nonobese group, the sensitivities of glucose transport and antilipolysis were reduced in both the obese nondiabetic and obese diabetic groups. Compared with the obese nondiabetic subjects, the ED50 for stimulation of glucose transport was higher in the obese patients with NIDDM (171 +/- 38 vs. 92 +/- 10 pM, P less than 0.005). In contrast, the ED50s for antilipolysis were similar in obese diabetic patients (32 +/- 6 pM) and obese nondiabetic subjects (27 +/- 3 pM). No difference was found in insulin binding in patients with NIDDM when compared with the equally obese nondiabetic subjects. These data indicate 1) the mechanism of insulin resistance differs in NIDDM and obesity, and 2) the selective loss of insulin sensitivity in NIDDM precludes changes in insulin binding as a cause of insulin resistance in this disorder.

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

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

Free fatty acid metabolism and obesity in man: in vivo in vitro comparisons.

We have examined the relationship of free fatty acid (FFA) turnover and lipid oxidation rates in vivo to the size of body triglyceride stores and compared these findings with the in vitro lipolytic rates of isolated abdominal fat cells. The studies were performed in 20 Pima Indian women 18 to 35 years of age, both lean and obese. FFA turnover rate was measured using a 1-14C-palmitate infusion, lipid oxidation rate by indirect calorimetry using a ventilated hood, body composition by underwater weighing with correction for residual lung volume, and fat cell lipolytic rates in vitro by published methods. Both FFA turnover and lipid oxidation rates, expressed per kg of body fat, decreased with increasing degree of obesity (as measured by percent body fat) (r = -0.90, and r = -0.75, P less than or equal to 0.0001, respectively). In contrast, the rate of lipolysis determined in vitro, expressed per kg of fat, increased with increasing degree of obesity (r = 0.58, P less than 0.01). A ratio of FFA turnover/lipolysis, which directly compares these in vivo and in vitro measurements, decreased significantly with increases in the degree of obesity (r = -0.81, P less than or equal to 0.0001). Furthermore, there were no positive correlations between the measures of in vivo FFA metabolism and in vitro lipolysis when both were expressed per fat mass, per fat cell number, or per fat cell surface area. The in vivo data also demonstrated that lipid oxidation could only account for 50% of the FFA disappearance rate. While lipid oxidation rate adjusted to the metabolic size increased with increasing plasma FFA concentration (r = 0.75, P less than 0.0003), the nonoxidative component of the FFA turnover failed to increase with increases in plasma FFA concentration (P = 0.5). We conclude that FFA is not available in vivo in proportion to the size of the triglyceride stores. The reason for this is not due to an inability of fat cells to release their stored triglyceride as assessed in vitro. Hence, in vitro measurements of fat cell lipolysis cannot be used to directly predict in vivo FFA metabolism. The large nonoxidative FFA disposal is likely to be important in the regulation of plasma FFA concentrations.

Adipose Tissue↗
PubMed1986

Overnutrition induced decrease in insulin action for glucose storage: in vivo and in vitro in man.

The effect of short-term overnutrition on insulin action for glucose disposal was assessed in 15 Southwest American Indians (mean wt = 74 +/- 6 kg). After two weeks of weight maintenance and again after two weeks of 62% greater caloric intake (constant ratio of fat:carbohydrate:protein), insulin action for glucose disposal was measured using the euglycemic clamp technique with plasma insulin concentrations of about 110 and 1800 uU/mL. Simultaneous indirect calorimetry was used to estimate carbohydrate oxidation and storage rates. Following overnutrition, mean weight gain was 3.0 +/- 0.2 kg, P less than 0.01. Overnutrition induced a decrease in glucose storage at the low and high insulin concentrations: 1.2 +/- 0.3 to 0.2 +/- 0.3, P less than 0.01, and 6.4 +/- 0.3 to 4.3 +/- 0.5, mg/kg FFM min, P less than 0.001. Carbohydrate oxidation was significantly increased at both insulin concentrations. The mean total insulin mediated glucose disposal rate decreased from 11.6 +/- 0.5 to 10.3 +/- 0.7, P less than 0.01, at the high insulin concentration. This decrease was due entirely to the reduction in carbohydrate storage and was correlated with increased fasting insulin concentration (r = 0.7, P less than 0.01). Overnutrition also induced a significant decrease in the percent muscle glycogen synthase active measured fasting and at the end of the high-dose insulin infusion. The results indicate that short-term overnutrition results in reduced insulin action for glucose storage and disposal which is correlated with increased fasting insulin concentrations. Reduced glycogen synthase activity may contribute to the effect of overnutrition on in vivo insulin-mediated glucose storage.

Adolescent↗
PubMed1986

Comparison of glucose metabolism in adipocytes from Pima Indians and Caucasians.

The present study was designed to compare various aspects of glucose metabolism of adipocytes isolated from 10 obese Pima Indians and 10 Caucasians. All 20 subjects had normal glucose tolerance, and the two groups were matched for sex, age, degree of obesity, and fasting plasma glucose and insulin concentrations. The results indicated that adipocytes from the two groups were comparable in average cell size, basal and maximum insulin-stimulated glucose transport, glucose metabolism at 5.5 mmol/L glucose, ED50 of insulin for glucose transport and the inhibition of lipolysis, basal lipolysis rates, and insulin binding. The similarity between the metabolic behavior of adipocytes isolated from Pimas and Caucasians suggests that the study of adipocytes from Pima Indians yields information that is relevant to the understanding of obesity in other populations.

Adipose Tissue↗
PubMed1986

Insulin sensitivity in adipocytes from subjects with varying degrees of glucose tolerance.

Previous studies showed that the sensitivity of glucose transport to insulin is lower in adipocytes isolated from subjects with noninsulin-dependent diabetes mellitus and impaired glucose tolerance compared with subjects with normal glucose tolerance. This study analyzed the relationship between insulin sensitivity of glucose transport and glycemia in a large group of nondiabetic-nonglucose-intolerant subjects with a wide range of glycemic response to oral glucose. Seventy-four Pima Indians with 2-h postglucose load glucoses between 77 and 197 mg/100 ml, fasting plasma glucoses between 76 and 108 mg/100 ml, and no postload glucoses less than 199 mg/100 ml were studied. Isolated adipocytes were prepared in vitro after an abdominal fat biopsy, ED50 of insulin for glucose transport was correlated with 2-h postload glucoses, but not between insulin binding per cell or per cell surface area or in ED50 of insulin for antilipolysis and 2-h postglucose load glucoses. Although only 17% of the variation in glucose tolerance could be explained by a change in the sensitivity of glucose transport to insulin, the data suggests that a postinsulin-binding defect in the coupling of insulin binding to glucose transport may be an early step in the development of insulin resistance in human adipocytes.

Adipose Tissue↗
PubMed1986

Determinants of 24-hour energy expenditure in man. Methods and results using a respiratory chamber.

Daily human energy requirements calculated from separate components of energy expenditure are inaccurate and usually in poor agreement with measured energy intakes. Measurement of energy expenditure over periods of 24 h or longer is needed to determine more accurately rates of daily energy expenditure in humans. We provide a detailed description of a human respiratory chamber and methods used to determine rates of energy expenditure over 24-h periods in 177 subjects. The results show that: fat-free mass (FFM) as estimated by densitometry is the best available determinant of 24-h energy expenditures (24EE) and explains 81% of the variance observed between individuals (24EE [kcal/d] = 597 + 26.5 FFM); 24EE in an individual is very reproducible (coefficient of variation = 2.4%); and even when adjusted for differences in FFM, there is still considerable interperson variability of the daily energy expenditure. A large portion of the variability of 24EE among individuals, independent of differences in body size, was due to variability in the degree of spontaneous physical activity, i.e., "fidgeting," which accounted for 100-800 kcal/d in these subjects.

Activities of Daily Living↗
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

Increased resting metabolic rates in obese subjects with non-insulin-dependent diabetes mellitus and the effect of sulfonylurea therapy.

Obese subjects with non-insulin-dependent diabetes mellitus (NIDDM) lose weight soon after diagnosis and tend to gain weight during hypoglycemic therapy. One explanation for these weight shifts is the change in caloric loss from glycosuria. We compared 24 obese Pima Indians with NIDDM to 24 Pima Indians with normal glucose tolerance to determine whether resting metabolic rate changes may be an additional factor influencing the weight shifts. The diabetic and nondiabetic subjects were equally obese, body fat 38 +/- 1% versus 37 +/- 1% (mean +/- SEM), respectively, as determined by densitometry. In the morning after an overnight fast, resting metabolic rate (RMR) was measured by indirect calorimetry. The mean RMR of the diabetic subjects, 32.9 +/- 0.5 kcal/day X kg fat-free mass (FFM), was 5% higher than that of the nondiabetic subjects, 31.4 +/- 0.5 kcal/day X kg FFM (P less than 0.05). In nine of the diabetic subjects, 6 wk of tolazamide therapy was associated with reductions in mean FPG, 253 +/- 16 to 144 +/- 14 mg/dl (P less than 0.01), mean daily urine glucose loss, 128 +/- 26 to 11 +/- 4 g (P less than 0.01), and mean RMR, 31.9 +/- 0.8 to 30.2 +/- 0.6 kcal/day X kg FFM (P less than 0.04). Weight of the subjects was maintained constant from beginning to end of therapy (106.5 +/- 9.6 versus 108.1 +/- 9.9 kg) by decreasing daily calorie intake from 3070 +/- 103 to 2784 +/- 163 kcal (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1985

The effects of short-term overfeeding on adipocyte metabolism in Pima Indians.

The effects on adipocyte metabolism of increasing daily caloric intake by approximately 60% for 14 days was studied in seven nondiabetic moderately obese southwestern Native American Indians. Mean body weight increased by 3.0 +/- 0.3 kg, without any change in average size of isolated abdominal adipocytes. Overfeeding resulted in a 58% increase (P less than 0.01) in mean fasting plasma insulin concentration, whereas fasting plasma glucose concentration remained constant. Basal and maximum (8 nmol/L) insulin-stimulated glucose transport rates by isolated adipocytes increased by 83% (P less than 0.02) and 110% (P less than 0.01), respectively, after overfeeding, associated with an increase of 118% (P less than 0.01) in the incremental response to maximal insulin stimulation. However, no differences in either the sensitivity (ED50 of insulin for the stimulation of glucose transport) or the responsiveness (percent stimulation by insulin) of glucose transport were seen in isolated adipocytes as a result of overfeeding. Maximum insulin-stimulated total glucose utilization rates by isolated adipocytes incubated at 5.5 mmol/L glucose were 63% greater after overfeeding, due to increases in lactate formation, triglyceride synthesis, and CO2 production. Mono125I-(Tyr A14)-insulin binding per cell and per cell surface area was similar before and after overfeeding. The lipolytic rate of isolated adipocytes, in the absence and presence of 25 nmol/L and 2 mumol/L isoproterenol, was decreased by 75% (P less than 0.02), 45% (P less than 0.05), and 27% (P less than 0.05), respectively, after overfeeding. However, overfeeding did not result in a significant difference in the sensitivity of antilipolysis to insulin.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗
PubMed1985

Relationship between degree of obesity and in vivo insulin action in man.

Previous studies have demonstrated reduced in vivo insulin action in obese subjects compared with lean controls. However, little data is available on the relationship between degree of obesity and insulin action, and this relationship has not been shown to be independent of individual differences in maximal aerobic capacity. We studied 55 male Pima Indians and 35 male Caucasians with normal glucose tolerance. In vivo insulin action was measured using the hyperinsulinemic, euglycemic clamp technique at a plasma insulin concentration of approximately 100 microU/ml. Body composition was determined by densitometry, and maximal aerobic capacity was estimated using a graded exercise test. The results showed that degree of obesity was nonlinearly related to in vivo insulin action. In both Indians and Caucasians there was a significant decline in insulin action with increasing obesity up to a percent body fat of approximately 28-30%. Further increases in obesity in the Indians were not associated with significant changes in insulin action. Maximal aerobic capacity was positively linearly correlated with insulin action over the entire range of insulin action in both racial groups. Degree of obesity and maximal aerobic capacity were each independently associated with insulin action although these independent relationships were of marginal significance in the Caucasians. Surprisingly, individual differences in obesity and maximal aerobic capacity accounted for only half the variability observed in insulin action in these glucose tolerant subjects.

Adult↗