PubMed Health⌕ Search

Biomedical subjects

F X Pi-Sunyer

Publications and source records attributed to F X Pi-Sunyer.

At least 91 records · Page 5Linked to original sources

Individual, but not simultaneous, glucagon and cholecystokinin infusions inhibit feeding in men.

Pancreatic glucagon and cholecystokinin octapeptide (CCK-8) were intravenously infused (1 ml/min for 10 min) alone or in combination beginning 15 min after normal-weight men had eaten a 500-ml tomato soup preload and 5 min before they were served a lunch of macaroni and beef with tomato sauce. Infusion of approximately 3 ng.kg-1.min-1 glucagon or approximately 2 ng.kg-1.min-1 CCK-8 each reduced test meal size. However, simultaneous infusion of these peptide doses reduced meal size less than the sum of the peptides' individual effects. Infusions of approximately 1.5 ng.kg-1.min-1 glucagon or approximately 1 ng.kg-1.min-1 CCK-8 had neither individual nor interactive effects on meal size. Psychophysical ratings failed to detect nonspecific side effects after any of the infusions. That exogenous glucagon and CCK-8 each reduced meal size without side effects suggests that these peptides may participate in the physiological control of human appetite; that their simultaneous infusion resulted in an infra-additive reduction in meal size suggests that they can interact antagonistically.

Adolescent↗

Cholecystokinin (CCK-8) affects gastric pressure and ratings of hunger and fullness in women.

Cholecystokinin (CCK) may affect food intake by augmenting neural activity from the distended stomach, thereby amplifying satiety signals. To test the hypothesis that subjects would report more fullness and less hunger with gastric distension when CCK-8 (112 ng/min) was infused than when saline was infused, a gastric balloon was inflated in the stomachs of four women. When the balloon was inflated to 500 ml, there was no difference in gastric pressure between the CCK-8 and saline conditions. Nonetheless, ratings of fullness were higher with CCK-8 administration. When the balloon was inflated to the maximum volume tolerated, the pressure rise was significantly smaller with CCK-8 infusion. In addition, fullness ratings rose and hunger ratings declined more steeply in relation to gastric pressure when CCK-8 was infused. In all conditions, gastric contractions were practically abolished with CCK-8 infusion. CCK-8 relaxed the stomach and concurrently sensitized the subjects to gastric pressure.

Adult↗

Independent effects of obesity and insulin resistance on postprandial thermogenesis in men.

The putative blunted thermogenesis in obesity may be related to insulin resistance, but insulin sensitivity and obesity are potentially confounding factors. To determine the independent effects of obesity and insulin resistance on the thermic effect of food, at rest and after exercise, lean and obese men were matched at two levels of insulin sensitivity determined by insulin-stimulated glucose disposal (milligrams per kilogram fat-free mass [FFM] per minute) during the euglycemic, hyperinsulinemic (40 mU/m2.min) clamp: 5.4 mg/kg FFM for the lean and obese groups with low insulin sensitivity, and 8.1 mg/kg FFM for the groups with high insulin sensitivity. The two lean groups were matched for percent fat (approximately 15 +/- 1% fat), as were the two obese groups (approximately 33 +/- 2% fat). Energy expenditure was measured for 3 h in the fasting state and for 3 h after a 720-kcal mixed meal, each at rest and immediately after 1 h of cycling at 100 W. The thermic effect of food (TEF) was calculated as the postprandial minus fasting energy expenditure (kcal/3 h) during rest and after exercise. During rest, TEF was blunted by both obesity (24 +/- 5 and 34 +/- 6 kcal/3 h for obese groups with low and high insulin sensitivity vs. 56 +/- 6 and 74 +/- 6 kcal/3 h for the lean groups with low and high insulin sensitivity; P less than 0.01 lean vs. obese) and insulin resistance (insulin-resistant less than insulin-sensitive, at both levels of obesity; P less than 0.01). After exercise, TEF was also impaired in the obese (47 +/- 6 and 44 +/- 5 kcal/3 h for the insulin-resistant and -sensitive groups) and in the lean insulin-resistant (55 +/- 5 kcal/3 h), compared with the lean insulin-sensitive men (71 +/- 3 kcal/3 h), P less than 0.01. Compared with rest, TEF after exercise was improved, but not normalized, in both obese groups (P less than 0.05), but unchanged in the lean groups. These results suggest that both insulin resistance and obesity are independently associated with impaired TEF at rest, but the responsiveness of thermogenesis to exercise before a meal is related to the obese state and not independently to insulin resistance per se.

Adult↗

Combination therapy for NIDDM with biosynthetic human insulin and glyburide.

OBJECTIVE: TO investigate the effects of the addition of glyburide to the regimen of insulin-treated non-insulin-dependent diabetes mellitus (NIDDM) patients with regard to their overall insulin requirement and dosage schedule and to assess persistence of these effects. RESEARCH DESIGN AND METHODS: A double-blind randomized parallel-groupo, placebo-controlled, 20-wk outpatient trial at the Clinical Research Unit (CRU) at St. Luke's/Roosevelt Hospital (New York). Subjects were 20 insulin-dependent NIDDM patients previously managed on insulin alone. After a baseline period of satisfactory diabetes control on biosynthetic human insulin alone, insulin dosage was halved, and patients were placed on a combination with either glyburide or placebo. Diabetes control equivalent to baseline was reestablished by adjusting insulin as required on subsequent visits to the CRU. RESULTS: Insulin requirements in the glyburide group decreased by 29 U at 14 wk compared with 9 U in the placebo group (P less than 0.05). At 20 wk, the decreases remained significant (25 vs. 11 U, respectively; P less than 0.05). The mean +/- SD reduction in insulin requirement in the glyburide group was relatively constant (25 +/- 10 U) and was not related to premedication insulin requirement. Successful response to glyburide was inversely correlated with initial serum alkaline phosphatase level. CONCLUSIONS: Glyburide reduces insulin requirements for 20 wk of combination therapy in NIDDM patients. Patients whose initial insulin requirement is less than or equal to 25 U have a 50% chance of achieving equivalent glycemic control on glyburide alone.

Aged↗

Role of insulin and glucagon in oxytocin effects on glucose metabolism.

Oxytocin (OT) infusion in normal dogs increases plasma insulin and glucagon levels and increases rates of glucose production and uptake. The purpose of this study was to determine whether the effects of OT on glucose metabolism were direct or indirect. The studies were carried out in normal, unanesthetized dogs in which OT infusion was superimposed on infusion of either somatostatin, which suppresses insulin and glucagon secretion, or clonidine, which suppresses insulin secretion only. Infusion of 0.2 microgram/kg/min of somatostatin suppressed basal levels of plasma insulin and glucagon and inhibited the OT-induced rise of these hormones by about 60-80% of that seen with OT alone. The rates of glucose production and uptake by tissues, measured with [6-3H] glucose, were significantly lower than those seen with OT alone, and the rise in glucose clearance was completely inhibited. Clonidine (30 micrograms/kg, sc), given along with an insulin infusion to replace basal levels of insulin, completely prevented the OT-induced rise in plasma insulin and markedly reduced the glucose uptake seen with OT alone, but did not reduce the usual increase in plasma glucose and glucagon levels or glucose production. To determine whether the OT-induced rise in plasma insulin was in response to the concomitant increase in plasma glucose, similar plasma glucose levels were established in normal dogs by a continuous infusion of glucose and an OT infusion was superimposed. OT did not raise plasma glucose levels further, but plasma insulin levels were increased, indicating that OT can stimulate insulin secretion independently of the plasma glucose changes. Studies by others have shown that the addition of OT to pancreatic islets or intact pancreas can stimulate insulin and glucagon secretion, indicating a direct effect. Our studies agree with that and suggest that in vivo, OT raises plasma insulin levels, at least in part, through a direct action on the pancreas. These studies also show that OT increases glucose production by increasing glucagon secretion and, in addition, a direct effect of OT on glucose production is likely. The OT-induced increase in glucose uptake is mediated largely by increased insulin secretion.

Analysis of Variance↗

Health implications of obesity.

The health risks of obesity increase with its severity and reach significance at a weight greater than 20% above optimal, by using life insurance tables, or at a body mass index greater than 27. Risks include hypertension, insulin resistance and diabetes mellitus, cardiovascular disease, hypertriglyceridemia, low high-density-lipoprotein cholesterol, and, in some studies, high total-and low-density-lipoprotein cholesterol. There is an increased mortality from endometrial cancer in women and from colorectal cancer in men. Chronic hypoxia and hypercapnia, sleep apnea, gout, and degenerative joint disease can occur with more severe obesity. The distribution of body fat is directly related to these health risks. Abdominal obesity is more dangerous than gluteal-femoral obesity because the amount of intraabdominal fat seems to determine much of the increased peril; therefore, risks of cardiovascular disease, stroke, hypertension, and diabetes increase with abdominal obesity, even independently of total fat mass.

Adipose Tissue↗

Meal size and frequency: effect on the thermic effect of food.

The effects of meal size and frequency on thermic effect of food (TEF) were examined in seven healthy normal-weight young women. Each volunteer consumed in random order one of two identical meals [3138 kJ (750 kcal), 54.5% carbohydrate, 14.0% protein, 31.5% fat]. One meal was taken over 10 min [large meal (LM)] whereas the other was taken in six equal portions of 523 kJ (125 kcal) at 30-min intervals over a 3-h period [small meals (SM)]. Metabolic rate was measured for 1 h before and every 30 min after the meal started for 5 h. When expressed as either kJ/min (kcal/min) or kJ/5h (kcal/5h), TEF was significantly higher in the LM day than in the SM day (P less than 0.05). We conclude that the temporal pattern in which a mixed caloric load is eaten affects the thermogenic response and may be an important determinant of energy balance after a meal.

Adult↗

Effect of a soup preload on reduction of food intake by cholecystokinin in humans.

Cholecystokinin octapeptide (CCK-8) or saline was intravenously infused for 5 min before and 5 min during a meal of macaroni and beef, served 20 min after a preload of either 100 or 500 g of soup to 12 nonobese men. Intake of the test meal was significantly lower when CCK-8 was given, following the larger preload, than after any of the other treatments. There were no significant differences among the other three treatment conditions. These results are consistent with the hypothesis that gastric, but not merely pregastric, stimulation interacts with CCK-8 to reduce food intake in humans. Although gastric filling seems to be the most likely stimulus for the interactive effect with CCK-8, other factors such as activation of nutrient-sensitive sites cannot be eliminated. In addition, hunger ratings were significantly lower immediately after the larger soup preloads than after the smaller. Hunger ratings after the soup also correlated better with test-meal intake after the large soup preloads with and without CCK-8 than after the smaller preloads. Hunger did not correlate significantly with test meal intake after the small soup preload with CCK-8. These results suggest that hunger ratings are more sensitive predictors of intake when the stomach is relatively full (i.e., after a large preload) than when it is relatively empty (i.e., after a small preload) at the time the hunger rating is taken.

Adult↗

Effect of exercise training on insulin sensitivity and glucose metabolism in lean, obese, and diabetic men.

To clarify the impact of vigorous physical training on in vivo insulin action and glucose metabolism independent of the intervening effects of concomitant changes in body weight and composition and residual effects of an acute exercise session, 10 lean, 10 obese, and 6 diet-controlled type II diabetic men trained for 12 wk on a cycle ergometer 4 h/wk at approximately 70% of maximal O2 uptake (VO2max) while body composition and weight were maintained by refeeding the energy expended in each training session. Before and 4-5 days after the last training session, euglycemic hyperinsulinemic (40 mU.m2.min-1) clamps were performed at a plasma glucose of 90 mg/dl, combined with indirect calorimetry. Total insulin-stimulated glucose disposal (M) was corrected for residual hepatic glucose output. Body weight, fat, and fat-free mass (FFM) did not change with training, but cardiorespiratory fitness increased by 27% in all groups. Before and after training, M was lower for the obese (5.33 +/- 0.39 mg.kg FFM-1.min-1 pretraining; 5.33 +/- 0.46 posttraining) than for the lean men (9.07 +/- 0.49 and 8.91 +/- 0.60 mg.kg FFM-1.min-1 for pretraining and posttraining, respectively) and lower for the diabetic (3.86 +/- 0.44 and 3.49 +/- 0.21) than for the obese men (P less than 0.001). Insulin sensitivity was not significantly altered by training in any group, but basal hepatic glucose production was reduced by 22% in the diabetic men. Thus, when intervening effects of the last exercise bout or body composition changes were controlled, exercise training per se leading to increased cardiorespiratory fitness had no independent impact on insulin action and did not improve the insulin resistance in obese or diabetic men.

Adipose Tissue↗

Resting metabolic rate and energy balance in amenorrheic and eumenorrheic runners.

This study investigated metabolic and nutritional factors in association with athletic menstrual dysfunction (AMD). Three groups of women were studied: amenorrheic runners (amenorrheic), eumenorrheic runners (eumenorrheic), and eumenorrheic sedentary controls (sedentary). Amenorrheic and eumenorrheic were similar in age, weight, percent body fat by hydrodensitometry, training pace and mileage, best 10 km race time, years running, and maximal oxygen consumption. When adjusted for body weight or for fat-free mass by analysis of covariance, RMR was significantly lower in amenorrheic than in eumenorrheic and sedentary. The daily caloric intakes of the groups did not differ significantly, but the amenorrheic scored significantly higher than the eumenorrheic and sedentary on a scale of aberrant eating patterns. Amenorrheic high mileage runners seem to have a less adequate diet than eumenorrheic runners but appear to maintain energy balance and stable weight through a reduction in RMR.

Adaptation, Physiological↗

Metabolic abnormalities in bulimia nervosa.

Resting metabolic rate was measured in a group of 22 women of normal body weight with bulimia nervosa and in 19 age-, sex-, and weight-matched control subjects. Mean resting metabolic rate of patients was significantly lower than that of controls (5162 +/- 928 vs 5636 +/- 449 kJ/24 h [1229 +/- 221 vs 1342 +/- 107 kcal/24 h]), as was mean fasting blood glucose level (4.0 +/- 0.6 vs 4.6 +/- 0.6 mmol/L). Mean basal thyrotropin level was significantly lower in patients than controls, but other thyroid indexes did not differ. There were no group differences in body fat mass, fat cell size, or lipoprotein lipase activity. These data suggest that there is a disturbance in energy regulation in bulimia nervosa. However, the origins and role of this disturbance in the pathophysiology of bulimia are unclear.

Adipose Tissue↗

Comparison of thermic effects of constant and relative caloric loads in lean and obese men.

Controversy regarding defective thermic effect of food (TEF) in obesity might be related to differences among studies in the caloric loads. To clarify further the role of blunted thermogenesis in obesity, responses to the same absolute caloric load (720 kcal) and a relative load, which was 35% of each subject's resting metabolic rate (RMR), were compared in 11 lean (L) and 11 obese (O) men. The relative load was slightly larger for O than L (752 +/- 27 vs 683 +/- 21 kcal; means +/- SEM, NS). TEF, calculated as 3-h postprandial minus fasting RMR, was greater for L than O for both the 720-kcal (69 +/- 4 vs 31 +/- 3 kcal/3 h, p less than 0.01) and relative loads (64 +/- 4 vs 37 +/- 3 kcal/3 h, p less than 0.01). For L, TEF was greater for the 720-kcal load than for the relative load whereas for O, TEF was greater for the relative than for the 720-kcal meal. However, expressed as a percent of the calories ingested, TEF for the absolute and relative meals was identical for each group, in both cases lower for O (4.2 +/- 0.4% vs. 4.7 +/- 0.3%) than for L (9.7 +/- 0.4% vs 9.3 +/- 0.8%); p less than 0.01. These results demonstrate the impact on thermogenesis of the basis on which the meal is dosed and provide further evidence for defective thermogenesis in obesity.

Adult↗

Acute effects of exercise on food intake in obese and nonobese women.

The animal model of exercise-induced anorexia was employed in humans to develop a laboratory paradigm for studying the acute effect of exercise on food intake. Each of nine obese and nine nonobese women exercised either strenuously (90 W) or moderately (30 W) on a cycle ergometer for 40 min or rested in the laboratory on each of 3 nonconsecutive days. Intake of a liquefied test meal (1.04 kcal/g) eaten 15 min after exercise was significantly less after the strenuous (620 g) than after the moderate (754 g) exercise in the nonobese women but was no different after the two conditions (532 g after strenuous, 581 g after moderate) in the obese women. Heart rate and energy expenditure were increased in proportion to the exercise by the same amount in both groups. The results demonstrate for the first time that food intake is reduced immediately after strenuous exercise in nonobese women, as it is in animals, and validate the feasibility of this laboratory paradigm.

Adult↗

Weight loss and change in resting metabolic rate.

The relation between change in resting metabolic rate (RMR) and change in fat-free mass (FFM) after weight loss is not well understood and is often inappropriately expressed in kilocalories per unit of FFM. We measured RMR and FFM in 35 obese patients enrolled in a conservative weight-loss program. RMR per kilogram FFM was not different after weight loss. However, the regression of delta RMR on delta FFM revealed that the decline in RMR tended to be greater than could be accounted for by loss of FFM. At initial test and retest, body fat (Fat) was not a predictor of RMR after FFM had been taken into account but delta Fat significantly contributed to the prediction of delta RMR when added to the equation after delta FFM. Thus, people losing larger amounts of weight had declines in RMR greater than could be accounted for by loss of FFM. Self-reported age of onset of obesity was not related to delta RMR.

Adipose Tissue↗

Obesity and diabetes in blacks.

Diabetes mellitus is more prevalent in the American Black population than in the White population. The prevalence is increasing in Blacks, and there is evidence that it is accompanied by a greater severity of diabetic complications. In addition, mortality figures are higher in Blacks, and Black women are more seriously affected than Black men. Although the reasons for this are unclear, some factors stand out as important. These include obesity, socioeconomic status, and genetics. Obesity is a severe problem in Blacks, particularly in women. Both the degree and the distribution of fat may contribute greatly to the prevalence of diabetes in Blacks. Although the prevalence of obesity is higher in the poor economic groups, multivariate analysis suggests that poverty cannot explain all of the excess obesity that occurs in the Black population. More research is needed into a possible genetic predisposition of Blacks to obesity and diabetes and into the interrelationship between the two conditions in this racial group.

Age Factors↗