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B V Howard

Publications and source records attributed to B V Howard.

At least 163 records · Page 9Linked to original sources
PubMed1987

Hyperglycemia stimulates carbohydrate oxidation in humans.

We examined whether hyperglycemia stimulates carbohydrate oxidation independent of insulin. Rates of total glucose disposal and substrate oxidation (indirect calorimetry) were measured at 4 insulin concentrations and at each level of insulin at 4 glucose concentrations in 88 separate studies in 22 normal volunteers. The insulin sensitivity of carbohydrate and lipid oxidation was independent of glycemia, but glucose, independent of insulin, increased the absolute rate of carbohydrate oxidation and decreased lipid oxidation. To compare the ability of glucose and insulin to stimulate carbohydrate oxidation, oxidation rates were examined at similar rates of total glucose disposal induced by hyperinsulinemia or hyperglycemia. At physiological matched rates of glucose disposal, insulin stimulated carbohydrate oxidation 2.4-fold more than glucose. The free fatty acids (FFA) were significantly lower in the presence of hyperinsulinemia than hyperglycemia. When compared at similar (supraphysiological) rates of total glucose disposal, where the FFA were completely suppressed, the rate of carbohydrate oxidation was related to the total rate of glucose disposal rather than the ambient glucose or insulin concentrations. We conclude that both glucose and insulin can increase carbohydrate oxidation in humans. We propose that the rate of carbohydrate oxidation is determined by FFA availability and by glucose availability independent of the FFA level in glucose-consuming tissues. Although FFA availability is almost solely determined by insulin, both glucose and insulin can increase carbohydrate oxidation by increasing glucose availability.

Blood Glucose↗
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

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

Effect of diet on energy expenditure and plasma norepinephrine in lean and obese Pima Indians.

To assess whether thermogenesis or sympathetic nervous system (SNS) function might differ between lean and obese human subjects, studies of thermic and sympathetic responses to standard stimuli were undertaken in Pima Indians, an ethnic group with a high prevalence of obesity. Plasma levels of norepinephrine (NE) and energy expenditure at rest and in response to feeding, exercise, and graded infusions of NE were compared in five lean and five obese Indians during a period of weight maintenance (WM), after 3 weeks of overfeeding (OF) and, in the obese, also after 6 weeks of underfeeding (UF). Basal energy expenditure, when adjusted for fat free mass, was equivalent during WM and increased 3% with OF (P less than 0.01) in both groups. Thermic responses to exercise or a test meal did not differ in lean and obese and did not change with OF, while thermic responses to NE infusion fell during OF to a greater degree in obese than lean (P less than 0.05). A similar pattern (decreased effect in obese with OF) was also noted in the glycemic response to infused NE (P less than 0.05). Although not quantitatively different in lean and obese, the plasma NE concentration appeared to vary more in response to feeding or dietary alteration in the obese than lean, a finding that may reflect lower plasma clearance of NE in the obese. These studies, therefore, raise the possibility that overfeeding in obese Pima Indians may limit the contribution of sympathetically mediated thermogenesis to energy expenditure, though the implications of this for body weight regulation are speculative.

Adolescent↗
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↗
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↗
PubMed1986

Effects of NIDDM on very-low-density lipoprotein triglyceride and apolipoprotein B metabolism. Studies before and after sulfonylurea therapy.

To evaluate mechanisms of diabetes-induced changes in very-low-density lipoprotein (VLDL), VLDL triglyceride (TG) and VLDL apolipoprotein B (apoB) metabolism were studied in 12 obese Pima Indian control subjects and in 15 Pima Indian obese non-insulin-dependent diabetics. Eleven of the diabetics were restudied after reduction of hyperglycemia with oral sulfonylurea therapy. In addition, adipose, muscle, and postheparin lipoprotein lipase and postheparin hepatic lipase activities were measured in all subjects. Obese diabetics as compared with obese controls showed a trend toward increased production of VLDL TG (46 +/- 4 vs. 35 +/- 6 g/day, P = .10) but not of VLDL apoB (1595 +/- 106 vs. 1597 +/- 164 mg/day, NS); production of VLDL TG declined to control levels (33 +/- 4 g/day, P less than .05) during therapy, whereas there was no change in production of VLDL apoB. Diabetics had a clearance defect for VLDL, indicated by significantly lower fractional catabolic rates for both VLDL TG (10.6 +/- .9 vs. 13.1 +/- .9 pools/day, P less than .05) and VLDL apoB (5.6 +/- .4 vs. 7.5 +/- 0.7, P less than .05) as compared with controls; fractional catabolic rates increased after therapy (to 13.3 +/- 1.5, P less than .05, and 6.7 +/- .4, P less than .05, respectively). In the diabetics, this decrease in clearance was accompanied by a lower adipose lipoprotein lipase (.30 +/- .09 vs. .92 +/- .25 mumol X g-1 X h-1, P less than .01), which increased during therapy (to .61 +/- .17, P less than .05). Hepatic lipase also decreased significantly after therapy (27.4 +/- 3.6 to 26.4 +/- 3.2, P less than .01). Composition of VLDL in diabetics was also abnormal, indicated by a higher TG/apoB ratio (14.7 +/- .6 vs. 11.7 +/- .8, P less than .01); this ratio fell during therapy (to 12.5 +/- .8, P less than .05). The data indicate there are multiple abnormalities in structure and metabolism of VLDL in non-insulin-dependent diabetics. Control of hyperglycemia with sulfonylureas has the capability of reversing some of these abnormalities.

Adult↗
PubMed1986

Compensatory mechanisms governing the concentration of plasma low density lipoprotein.

To evaluate factors regulating the concentrations of plasma low density lipoproteins (LDL), apolipoprotein B metabolism was studied in nine Pima Indians (25 +/- 2 yr, 191 +/- 20% ideal wt) with low LDL cholesterol (77 +/- 7 mg/dl) and apoB (60 +/- 4 mg/dl) and in eight age- and weight-matched Caucasians with similar very low density lipoprotein (VLDL) concentrations, but higher LDL (cholesterol = 104 +/- 18; apoB = 82 +/- 10; P less than 0.05). Subjects received autologous 131I-labeled VLDL and 125I-labeled LDL, and specific activities of VLDL-apoB, intermediate density lipoprotein (IDL)-apoB, and LDL-apoB were analyzed using a multicompartmental model. Synthesis of LDL-apoB was similar (1224 +/- 87 mg/d in Pimas vs 1218 +/- 118 mg/d in Caucasians) but in Pimas the fractional catabolic rate (FCR) for LDL-apoB was higher (0.48 +/- 0.02 vs 0.39 +/- 0.04 d-1, P less than 0.05). In the Pimas, a much higher proportion of VLDL-apoB was catabolized without conversion to LDL (47 +/- 3 vs 30 +/- 5%, P less than 0.01). When all subjects were considered together, LDL-apoB concentrations were negatively correlated with both FCR for LDL-apoB (r = -0.79, P less than 0.0001) and the non-LDL pathway (r = -0.43, P less than 0.05). Also, the direct removal (non-LDL) path was correlated with VLDL-apoB production (r = 0.49, P = 0.03), and the direct removal pathway and FCR for LDL-apoB were correlated (r = 0.49, P = 0.03). In conclusion, plasma LDL appear to be regulated by both the catabolism of LDL and the extent of metabolism of VLDL without conversion to LDL; both of these processes may be mediated by the apoB/E receptor, and appear to increase in response to increasing VLDL production.

Adult↗
PubMed1985

Effect of sulfonylurea therapy on plasma lipids and high-density lipoprotein composition in non-insulin-dependent diabetes mellitus.

To assess the effects of sulfonylurea therapy on plasma lipids and high-density lipoprotein composition, 11 obese diabetic Pima Indians with type II, or non-insulin-dependent, diabetes mellitus were studied before and after tolazamide therapy for one month. Diet composition and weight were kept constant, and the data were compared with a control group of 18 age-, sex-, and weight-matched non-diabetic subjects. Improvement of glycemic control was accompanied by significant decreases in total and very-low-density lipoprotein triglycerides. Total and low-density lipoprotein cholesterol also declined significantly, and there was an increase in the ratio of high-density lipoprotein to low-density lipoprotein cholesterol. Concentrations of total high-density lipoprotein cholesterol, phospholipid, and apolipoprotein AI were unchanged. An increase in the proportion of the high-density lipoprotein 2 subfraction, however, was suggested by significant increases in the ratios of high-density lipoprotein 2 to high-density lipoprotein 3 cholesterol and apolipoprotein AI. There was also a change in the composition of the high-density lipoprotein 2 particle, as indicated by changes in the molar ratio of cholesterol to apolipoprotein AI. The data suggest that improvement of glycemic control after sulfonylurea therapy, when weight and diet composition remain constant, reverses several of the lipoprotein abnormalities observed in type II diabetic patients. There was no evidence of changes in lipoproteins in directions associated with an increased risk for atherosclerosis.

Adipose Tissue↗
PubMed1985

Relationship between insulin-mediated glucose disposal and lipid metabolism in man.

To assess the possible effects of lipid metabolism on insulin-mediated glucose disposal, 18 nondiabetic Pima Indian women (age 18-35 yr) were studied using 1-14C-palmitate infusion to measure free fatty acid turnover rate followed by a euglycemic clamp (clamp) to measure in vivo insulin-mediated glucose disposal (M). Indirect calorimetry was performed in the basal state and during the clamp. This was used to assess glucose oxidation rate, lipid oxidation rate, and to calculate nonoxidative glucose disposal (storage). Basal and clamp lipid oxidation rate correlated with basal plasma free fatty acid concentration (r = 0.81, P less than or equal to 0.0001, r = 0.67, P less than 0.003, respectively). The fall in lipid oxidation was highly correlated with the increase in glucose oxidation during the insulin infusion (r = 0.96, P less than or equal to 0.0001). The clamp lipid oxidation rate negatively correlated with the glucose oxidation rate (r = -0.85, P less than 0.0001) and with the M value (r = -0.60, P less than 0.01) but was not correlated with the clamp glucose storage (r = -0.2, P = 0.4). On the other hand, glucose storage appeared to make a greater contribution to the difference in M value between the upper and lower extremes of M than did glucose oxidation, as evidenced by an increase in glucose storage of 0.59 mg/kg fat-free mass times minute per 1 mg/kg fat-free mass times minute increase in glucose disposal. The M value was negatively correlated with obesity as measured by percent body fat (r = -0.64, P less than 0.004), but neither basal free fatty acid concentration, basal free fatty acid turnover, basal lipid oxidation, nor clamp lipid oxidation correlated with percent body fat. We conclude that an interaction of lipid and glucose metabolism in a glucose fatty acid cycle, as proposed by Randle et al. (1), may be operative in the regulation of glucose oxidation in man. The disposal of glucose however has two components. The storage component does not appear to be associated with lipid oxidation in the way that the oxidative component is and may be regulated by a different mechanism. Since the results show that the glucose storage component plays a significant role in distinguishing between those with low and high M values, we suggest that the glucose fatty acid cycle can, at best, only partially explain impaired in vivo insulin-mediated glucose disposal. Furthermore, the data suggest that the impact of obesity on in vivo insulin resistance appears to be mediated by factors other than changes in lipid availability or metabolism.

Adolescent↗
PubMed1985

Development of an integrated model for analysis of the kinetics of apolipoprotein B in plasma very low density lipoproteins, intermediate density lipoproteins, and low density lipoproteins.

To quantify more precisely the metabolism of apolipoprotein B (apo B) in human beings, an integrated model was developed for the analysis of the isotope kinetics of apo B in very low density lipoproteins (VLDL), intermediate density lipoproteins (IDL), and low density lipoproteins (LDL). The experimental basis for model development was a series of 30 triple-isotope studies in which patients received autologous 131I-VLDL, 125I-IDL, and [3H]glycerol as a precursor of VLDL triglycerides. The currently proposed model contains the following components: (a) a VLDL delipidation cascade that has a variable number of subcompartments, (b) a slowly catabolized pool of VLDL, (c) an IDL compartment consisting of two closely connected subcompartments, one of which is outside the immediate circulation, and (d) a two-compartment subsystem for LDL. Because mass data indicate that not all VLDL were converted to LDL, the model allows for irreversible removal of apo B from VLDL (or IDL) subsystems. It accounts for apparent "direct" input of LDL by postulating an early, rapidly metabolized compartment of VLDL that is converted directly to IDL. The model appears to be consistent with specific activity curves from the current triple-isotope studies and with present concepts of lipoprotein physiology; it also can be used to quantify pathways of lipoprotein apo B transport in normal and abnormal states.

Apolipoproteins B↗
PubMed1985

Influence of obesity on the metabolism of apolipoprotein B in humans.

The influence of obesity on the metabolism of apolipoprotein B (apo B) in very low density lipoprotein (VLDL), intermediate density lipoprotein (IDL), and low density lipoprotein (LDL) was investigated in nine obese and seven nonobese Pima Indian men. Kinetics of VLDL-apo B (VLDL-B), VLDL-triglycerides, IDL-B and LDL-B were studied after injection of autologous 131I-VLDL, [3H]glycerol, and autologous 125I-LDL. Specific activities were measured in apo B isolated from all lipoprotein fractions and in triglyceride isolated from VLDL. Transport rates and fractional catabolic rates for apo B in VLDL, IDL, and LDL and triglyceride in VLDL were determined by multicompartmental analysis. This method also allowed the estimation of rates of interconversions of the lipoproteins. The two groups had similar mean ages and heights, but the obese group had a higher total body weight (131 +/- 14 vs. 66 +/- 3 kg +/- SEM) and fat free mass (81 +/- 5 vs. 54 +/- 2 kg) than lean controls. Plasma total lipids were similar for the two groups, and apo B concentrations in VLDL, IDL, and LDL were similar in obese and lean subjects. In spite of similarity in concentrations, obese subjects compared to lean subjects had higher synthetic rates of VLDL-triglyceride (62.6 +/- 15 vs. 26.2 +/- 7 g/d, P less than 0.01), VLDL-B (2,241 +/- 215 vs. 1,113 +/- 72 mg/d, P less than 0.001), and LDL-B (1,234 +/- 87 vs. 802 +/- 83 mg/d, P less than 0.01). Furthermore, in obese subjects, significantly higher amounts of VLDL-B were removed from the circulation without conversion to LDL-B (1,078 +/- 159 vs. 460 +/- 34 mg/d, P less than 0.05), and obese subjects had a higher fractional catabolic rate for LDL than the lean controls (0.48 +/- 0.02 vs. 0.41 +/- 0.02 d-1, P less than 0.05). The rapid catabolism of LDL and increased metabolism of VLDL without conversion to LDL in obese individuals may be mechanisms for maintenance of LDL at normal levels despite the overproduction of its precursor.

Adult↗
PubMed1985

Multiple disturbances of free fatty acid metabolism in noninsulin-dependent diabetes. Effect of oral hypoglycemic therapy.

To assess the mechanisms for the elevation of free fatty acids in noninsulin-dependent diabetes, free fatty acid metabolism and lipid and carbohydrate oxidation were compared in 14 obese diabetic Pima Indians and in 13 age-, sex-, and weight-matched nondiabetics. The studies were repeated in 10 of the diabetics after 1 mo of oral hypoglycemic therapy. Fasting plasma glucose concentrations were elevated in diabetics (242 +/- 14 vs. 97 +/- 3 mg/dl, P less than 0.01) and decreased to 142 +/- 12 (P less than 0.01) after therapy. Fasting free fatty acid concentrations were elevated in diabetics (477 +/- 26 vs. 390 +/- 39 mumol/liter, P less than 0.01) and declined to normal values after therapy (336 +/- 32, P less than 0.01). Although free fatty acid transport rate was correlated with obesity (r = 0.75, P less than 0.001), the transport of free fatty acid was not higher in diabetics than in nondiabetics and did not change after therapy. On the other hand, the fractional catabolic rate for free fatty acid was significantly lower in untreated diabetics (0.55 +/- 0.04 vs. 0.71 +/- 0.06 min-1, P less than 0.05); it increased after therapy to 0.80 +/- 0.09 min-1, P less than 0.05, and was inversely correlated with fasting glucose (r = -0.52, P less than 0.01). In diabetics after therapy, lipid oxidation rates fell significantly (from 1.35 +/- 0.06 to 1.05 +/- 0.01 mg/min per kg fat-free mass, P less than 0.01), whereas carbohydrate oxidation increased (from 1.21 +/- 0.10 to 1.73 +/- 0.13 mg/min per kg fat-free mass, P less than 0.01); changes in lipid and carbohydrate oxidation were correlated (r = 0.72, P less than 0.02), and in all subjects lipid oxidation accounted for only approximately 40% of free fatty acid transport. The data suggest that in noninsulin-dependent diabetics, although free fatty acid production may be elevated because of obesity, the elevations in plasma free fatty acid concentrations are also a result of reduced removal, and fractional clearance of free fatty acid appears to be closely related to diabetic control. Furthermore, the increase in fractional clearance rate, despite a marked decrease in lipid oxidation, suggests that the clearance defect in the diabetics is due to an impairment in reesterification, which is restored after therapy.

Adult↗
PubMed1984

Hyperlipemia and arteriosclerotic cardiovascular disease in the Polynesian population of Rarotonga.

Total cholesterol, total triglyceride and high density lipoprotein (HDL) cholesterol and their relation to arteriosclerotic cardiovascular disease (ASCVD) were investigated in a population of Polynesian Maoris in Rarotonga who are becoming increasingly westernized. 8.5% of the population had plasma triglyceride elevations (triglyceride greater than or equal to 200 mg/dl), and the occurrence of hypertriglyceridemia was significantly higher in males than females. 5.8% of the population had elevations of total cholesterol (cholesterol greater than or equal to 250 mg/dl), and the proportion with elevation of total cholesterol was similar for males and females. 3.2% of the population had elevations of both triglyceride and cholesterol. HDL cholesterol concentrations were relatively low, and no sex differences were observed at any age. Analysis of lipoprotein cholesterol and triglyceride in a subset of those who had hyperlipemia indicated that the elevations of total cholesterol and triglyceride were mainly due to elevations of low density lipoprotein (LDL) cholesterol and very low density lipoprotein (VLDL) triglyceride, respectively; furthermore, elevations of VLDL triglyceride and LDL cholesterol were significantly correlated with increase in VLDL apolipoprotein B (apo B) and LDL apo B, respectively. Although an appreciable prevalence of diabetes was observed in this population (male: 6.7%, female: 8.4%), the diabetes could not account for the hyperlipemia. Among 693 subjects between the ages of 30 and 59 years, approx. 3% of males and 1% of females had Q-wave changes, and 16% of females and 4% of males had ST-T changes. Among males with Q-wave abnormalities, hyperlipemia was more frequent. There was also increased frequency of hypertension in those with elevated lipids. The data indicate the occurrence of some hyperlipemia in this population which could be of the familial-combined type; the elevated plasma lipids may contribute to the increased frequency of coronary heart disease.

Adult↗
PubMed1984

Sodium-potassium pump in cultured fibroblasts from obese donors; no evidence for an inherent decrease of basal or insulin-stimulated activity.

Na, K-ATPase activity may have a significant role in cellular thermogenesis. Reduced thermogenesis and an increased accumulation of unused calories in the form of fat could result from reduced basal or insulin-stimulated Na,K-ATPase activity in obese insulin-resistant man. We have previously demonstrated reduced Na,K-ATPase activity in intact red cells and their isolated membranes from obese humans. To determine if the reduced enzyme activity in obese subjects is the result of inherent cellular defects in the regulation of Na,K-pump activity, basal and insulin-stimulated rates of ouabain-inhibitable Rb uptake were measured in diploid fibroblasts from subjects with a range of body mass indices (BMI). Cell cultures were established from five extremely obese subjects (BMI greater than 40 kg/m2) with fasting hyperinsulinemia (38 +/- 6 microU/mL) and in four control (BMI less than 30 kg/m2) normoinsulinemic (14 +/- 3 microU/mL) subjects. Basal (17 +/- 3 v 23 +/- 2 nmol/L/min/10(10) cells +/- SEM) and maximal insulin-stimulated Na,K-pump activities (26 +/- 3 v 32 +/- 3 nmol/L/min/10(10) cells) were similar in the obese and control subjects. Maximal insulin stimulation for both groups was observed in four to eight minutes, and one-half maximal response required 2.5 ng/ml insulin. Cell density was negatively correlated with basal (r = 0.75, p less than 0.001) and maximally stimulated Na,K-pump activity (r = -0.73, p less than 0.001). Adjustment for this relationship did not influence the conclusions. Comparison of the results from the obese and control groups indicates (a) no evidence for an intrinsic cellular difference in basal Na,K-pump activity related to obesity and (b) no difference in insulin regulation of Na,K-pump activity, in fibroblasts from obese subjects.

Adult↗
PubMed1984

Relationships between insulin secretion, insulin action, and fasting plasma glucose concentration in nondiabetic and noninsulin-dependent diabetic subjects.

The relationships between insulin secretion, insulin action, and fasting plasma glucose concentration (FPG) were examined in 34 southwest American Indians (19 nondiabetics, 15 noninsulin-dependent diabetics) who had a broad range of FPG (88-310 mg/100 ml). Fasting, glucose-stimulated, and meal-stimulated plasma insulin concentrations were negatively correlated with FPG in diabetics but not in nondiabetics. In contrast, fasting and glucose-stimulated plasma C-peptide concentrations did not decrease with increasing FPG in either group and 24-h urinary C-peptide excretion during a diet of mixed composition was positively correlated with FPG for all subjects (r = 0.36, P less than 0.05). Fasting free fatty acid (FFA) was correlated with FPG in nondiabetics (r = 0.49, P less than 0.05) and diabetics (r = 0.77, P less than 0.001). Fasting FFA was also correlated with the isotopically determined endogenous glucose production rate in the diabetics (r = 0.54, P less than 0.05). Endogenous glucose production was strongly correlated with FPG in the diabetics (r = 0.90, P less than 0.0001), but not in the nondiabetics. Indirect calorimetry showed that FPG was also negatively correlated with basal glucose oxidation rates (r = -0.61, P less than 0.001), but positively with lipid oxidation (r = 0.74, P less than 0.001) in the diabetics. Insulin action was measured as total insulin-mediated glucose disposal, glucose oxidation, and storage rates, using the euglycemic clamp with simultaneous indirect calorimetry at plasma insulin concentrations of 135 +/- 5 and 1738 +/- 59 microU/ml. These parameters of insulin action were significantly, negatively correlated with FPG in the nondiabetics at both insulin concentrations, but not in the diabetics although all the diabetics had markedly decreased insulin action. We conclude that decreased insulin action is present in the noninsulin-dependent diabetics in this population and marked hyperglycemia occurs with the addition of decreased peripheral insulin availability. Decreased peripheral insulin availability leads to increased FFA concentrations and lipid oxidation rates (and probably also increased concentrations of gluconeogenic precursors) that together stimulate gluconeogenesis, hepatic glucose production, and progressive hyperglycemia.

Adolescent↗
PubMed1984

The antilipolytic action of insulin in obese subjects with resistance to its glucoregulatory action.

To compare the ability of insulin to regulate lipolysis in lean and obese subjects, free fatty acid (FFA) suppression was compared in groups of six lean [body mass index, 25.7 +/- 1.1 (+/-SEM) kg/m2] and six obese (body mass index, 48.8 +/- 3.1) Pima Indians during euglycemic hyperinsulinemic clamps which increased plasma insulin levels approximately 10, 20, and 100 microU/ml above basal concentrations. Basal FFA concentrations were slightly, but not significantly, elevated in the obese group (445 +/- 35 vs. 406 +/- 40 mu eg/liter). The mean decline in FFA from basal after 60-90 min of insulin infusion in the obese group was somewhat less than that in the lean group at the lower doses [67 +/- 23 vs. 132 +/- 32 (P = NS) during the 10-microU clamp, and 144 +/- 39 vs. 217 +/- 20 (P = NS) during the 20-microU clamp] and was almost identical in the two groups during the 100-microU clamp (226 +/- 29 vs. 229 +/- 51). In contrast, insulin-mediated glucose disposal at all insulin increments was much lower in the obese group (0.33 +/- 0.03, 0.56 +/- 0.04, and 1.39 +/- 0.04 mg/kg X min) than in the lean group (0.78 +/- 0.06, 1.67 +/- 0.12, and 4.96 +/- 0.26; P less than 0.001). The data suggest that although the obese subjects exhibited significant resistance to the glucoregulatory action of insulin, there were only small changes in insulin's antilipolytic effects. Relative maintenance of sensitivity to the antilipolytic action of insulin in the presence of resistance to insulin's glucoregulatory action could maintain fat deposition in obese individuals.

Fatty Acids, Nonesterified↗