Serum lipid and lipoprotein profile of patients with glycogen storage disease types I, III and IX.

With current dietary therapy, life expectancy in glycogen storage disease (GSD) has improved considerably and more children reach adulthood. Notwithstanding intensive dietary therapy, moderate to severe hyperlipidaemia is still observed frequently. There is limited information about the type and extent of hyperlipidaemia. We studied the lipid profile in 20 patients, aged 8-54 years, of the three (types I, III and IX) most common forms of adult GSD. Hyperlipidaemia was shown to be type-specific, affecting predominantly patients with GSD type Ia, who showed marked combined hypercholesterolaemia and hypertriglyceridaemia. By contrast, a heterogeneous distribution of HDL was found in patients with GSD I and III. There was no significant difference in Apo Al and Apo B concentrations between groups. In addition, mass measurements of the fractions of VLDL1, VLDL2 and IDL were raised in all patients with GSD Ia by comparison with all other patients with GSD. Patients with GSD type Ia have lipid concentrations and individual mass measurements that are consistent with ranges found in patients who have a significant risk of atherosclerosis. Accumulated evidence, however, suggest GSD type Ia patients do not have an increased risk of atherosclerotic cardiovascular disease (CVD) but the reason remains unknown. Intervention to reduce their lipid levels could therefore be on the basis of seeking to prevent the risk of pancreatitis rather than that of CVD.

Bone mineral density and markers of bone turnover in patients with glycogen storage disease types I, III and IX.

Patients with glycogen storage disease (GSD) types I, III and IX show reduced bone mineral content, but there is scarce data on new serum and urine markers of bone turnover or their relationship to bone densitometry. Six GSD I, four GSD III and four GSD IX patients underwent bone mineral density (BMD) measurement by dual-energy X-ray absorptiometry. Free pyridinoline (fPYD):creatinine and free deoxypyridinoline (fDPD):creatinine ratios were analysed on random urines. Procollagen type I C-terminal propeptide, procollagen type I N-terminal propeptide (PINP), carboxyterminal telopeptide of type I collagen and bone-specific alkaline phosphatase were analysed in serum. Some GSD I and GSD III patients had low or very low BMD. There was no difference in total body BMD z-score between the GSD types after adjusting for height (p=0.110). Bone marker analysis showed no consistent pattern. Urine fPYD:creatinine ratio was raised in four GSD I and two GSD III patients, while serum PINP was inappropriately low in some of these patients. There was no clear correlation between any markers of bone destruction and total body z-score, but the patient with the lowest total body z-score showed the highest concentrations of both urinary fPYD:creatinine and fDPD:creatinine ratios. We conclude that some GSD I and GSD III patients have very low bone mineral density. There is no correlation between mineral density and bone markers in GSD patients. The inappropriately low concentration of PINP in association with the raised urinary fPYD:creatinine and fDPD:creatinine ratios seen in two GSD I patients reflect uncoupling of bone turnover. All these findings taken together suggest that some GSD I and GSD III patients may be at an increased risk of osteoporosis.

Beneficial effects of pharmacotherapy on weight loss, depressive symptoms, and eating patterns in obese binge eaters and non-binge eaters.

OBJECTIVE: The purpose of this study was to compare the impact of drug therapy on weight loss, Beck Depression Inventory (BDI) scores, and binge eating patterns (BES) between obese binge eaters and non-binge eaters. RESEARCH METHODS AND PROCEDURES: 22 severe binge eaters, 17 moderate binge eaters, and 16 non-binge eaters received phentermine resin 15mg/day and dl-fenfluramine 20mg three times daily over a 6 month period for weight loss. All data are reported as mean+/-S. RESULTS: The percent weight loss compared to baseline within the 3 groups ranged from 8.9% to 11.3% at 3 months and 10.6% to 14.9% at 6 months. After 6 months, 73% of the severe binge eaters, 59% of moderate binge eaters and 69% of non-binge eaters had experienced more than 10% weight loss. BDI scores were significantly higher in the severe group at baseline when compared to non-binge eaters (p<0.006). After 3 and 6 months BDI scores improved in all groups but remained significantly different between the severe and non-binge eaters until the 6-month assessment. BES scores declined in all groups over the 6-month period. Echocardiograms were performed in 35 of 55 subjects following reports of a possible association between fenfluramine and valvular changes. Fifteen (43%) of subjects had no abnormal findings and 20 (57%) had evidence of valvular insufficiency occurring in one or more valves. Seven patients (20%) had significant valve damage according to the DHHS and FDA criteria. CONCLUSION: After 24 weeks of treatment severe binge eaters improved their eating pattern, depression scores, and achieved weight loss similar to non-binge eaters. These data suggest that pharmacologic intervention for weight loss and subsequent weight maintenance can be as successful in binge eaters as non-binge eaters. A relationship was seen between duration of drug treatment and valvular insufficiency in subjects treated for an average of 52 weeks. These findings validate the FDA requirement for studies of at least 1 year duration to evaluate both the safety and efficacy of pharmacologic treatment for obesity.

Gastric Bypass and Vertical Banded Gastroplasty- a Prospective Randomized Comparison and 5-Year Follow-up.

BACKGROUND: a prospective randomized study was undertaken to compare the outcome of vertical banded gastroplasty (VBG) and gastric bypass (GBP) in patients with clinically severe obesity. METHODS: eligibility criteria included Class IV obesity, < 50 years old and a history of at least one attempt of non-operative weight loss. Patients were managed conservatively for 3 months prior to surgery. Patients were followed post-operatively and monitored for early and late complications and their weight loss outcome for up to 5 years. RESULTS: 44 patients were recruited. Two patients withdrew within 4 weeks and were excluded. Twenty subjects had a GBP and 22 a VBG. There were no significant differences with respect to age, gender, maximum or pre-operative weight between the groups (p > 0.05). Patients who underwent GBP demonstrated significantly greater post-operative weight loss (p < 0.05) which was apparent from 6 months onwards. There were no deaths, pulmonary emboli, post-operative leaks or wound dehiscence. There were no instances of staple-line disruption. Symptomatic ulcer disease, confirmed endoscopically, developed in 25% of GBP patients. Nine patients developed gallstones post-operatively of whom five were in the VBG and four in the GBP group. CONCLUSIONS: weight loss following GBP was maintained, while VBG patients slowly regained.

Food intake and energy expenditure in obese female bingers and non-bingers.

Since compulsive eating occurs in approximately 30% of obese females and is associated with earlier relapse following weight loss, we compared daily energy intake, dietary composition and energy expenditure among obese binge eaters and obese non-bingers. Nine obese bingers (33 +/- 4 yrs, 95 +/- 6 kg, 39 +/- 1% fat) and nine obese non-bingers (47 +/- 3 yrs, 93 +/- 5 kg, 40 +/- 1% fat) were admitted for 12 days to a metabolic unit. Binge eaters were defined as scoring > 25 on the binge eating scale (BES). During the initial 8 days, subjects ate ad libitum from two computerized vending machines offering a variety of foods and beverages. A weight maintenance diet was then provided for the next 4 days. Twenty-four hour energy expenditure (24EE) and respiratory quotient (24Q) were measured on the last day of both feeding periods in a respiratory chamber. Obese bingers showed a wider range of energy intake compared to non-bingers, but the mean daily energy intake was similar between the two groups (2587 +/- 454 vs 2386 +/- 201 kcal/d) during 8 days of ad libitum intake. 24EE was not different between bingers and non-bingers after 8 days of ad libitum intake (2298 +/- 147 vs 2109 +/- 97 kcal/d, P = 0.3) or 4 days of weight maintenance diet, even more so after adjustment for differences in fat-free mass, fat mass and age. Resting metabolic rate, sleeping metabolic rate, and macronutrient intake and oxidation were also similar between groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of phenylpropanolamine on energy expenditure and weight loss in overweight women.

The effect of phenylpropanolamine (PPA), a noncatecholamine sympathomimetic weight-loss agent, on energy expenditure (EE) and substrate oxidation was measured in a respiratory chamber in 24 overweight women after 4 d of treatment (PPA or placebo) during weight maintenance and after 7 wk of treatment on a hypoenergetic diet (70% of measured baseline 24-h EE). Twelve women (37 +/- 2 y, 74 +/- 6 kg, 33 +/- 1% body fat) were randomly assigned to the PPA group [75 mg osmotic release oral system (OROS)-PPA/d] and 12 (mean +/- SEM: 38 +/- 2 y, 79 +/- 1 kg, 37 +/- 1% body fat) to the placebo group. Baseline measurements of 24-h EE (7849 +/- 226 vs 7834 +/- 142 kJ/d), basal metabolic rate (BMR) and 24-h respiratory quotient (RQ) were comparable between PPA and placebo groups. After 4 d of treatment, there was no significant effect of PPA on 24-h EE, BMR, and 24-h RQ compared with placebo. Over the 7-wk diet period, however, the PPA group (n = 8) had greater weight loss than the placebo group (n = 10): -5.0 +/- 0.5 vs -3.0 +/- 0.4 kg (P < 0.05). The changes in 24-h EE and 24-h RQ over the 7 wk were not different between the groups. We conclude that weight loss is enhanced by OROS-PPA, but this change was not explained by changes in 24-h EE or 24-h RQ. The small number of subjects may have hindered detection of subtle differences in energy metabolism.

Comparison of bulimics, obese binge eaters, social phobics, and individuals with panic disorder on comorbidity across DSM-III-R anxiety disorders.

Eighty-two women, presenting as normal-weight bulimics, obese binge eaters, social phobics, and individuals with panic disorder, were compared on anxiety, depression, and substance abuse. All were administered the Anxiety Disorder Interview Schedule-Revised and completed the Michigan Alcohol Screening Test, Drug Abuse Screening Test, and Self-Consciousness Scale. A striking proportion of eating disorder subjects were comorbid for one or more anxiety disorders, the most frequent diagnoses being generalized anxiety disorder and social phobia. The results suggest that the place of anxiety in bulimia nervosa goes beyond that discussed within the context of the anxiety reduction model. Conflicting comorbidity findings among this and prior investigations are noted, however, and discussed in terms of the issue of differential diagnosis between eating and anxiety disorders.

Evaluation of vitamin A absorption by using oil-soluble and water-miscible vitamin A preparations in normal adults and in patients with gastrointestinal disease.

We evaluated vitamin A absorption in 50 healthy adults and 26 gastrointestinal-disease patients by measuring the postabsorptive response in plasma retinyl esters after oral doses of the vitamin. On 3 consecutive days, two physiologic-dose tests of 2000-2400 retinol equivalents (RE) and one pharmacologic-dose test (84,000 RE) were administered. The physiologic doses were given as an oil-soluble or a water-miscible preparation. In gastrointestinal-disease patients the physiologic-dose test was highly correlated with the pharmacologic-dose test for the oil-soluble preparation as determined by peak rise (r = 0.50, P less than 0.05) and area under the curve (r = 0.56, P less than 0.01), suggesting that the physiologic dose is valid for investigating vitamin A absorption. Intestinal-disease or resection patients absorbed preparations poorly. Pancreatic-disease patients absorbed the oil-soluble preparation poorly. Physiologic rather than pharmacologic doses of vitamin A can be used to study vitamin A absorption.

Food intake measured by an automated food-selection system: relationship to energy expenditure.

Measuring food intake in a laboratory usually involves limited food choices. An automated food-selection system with two vending machines containing a large variety of foods was used to measure food intake in 10 male volunteers (31 +/- 6 y, 69.2 +/- 7.1 kg, 18 +/- 7% fat, mean +/- SD) on a metabolic ward. The effect of carbohydrate, fat, and protein intakes on 24-h energy expenditure (24EE) and substrate oxidations was measured in a respiratory chamber during day 4 of weight maintenance and day 7 of ad libitum intake. Ad libitum intake resulted in a 7-d overfeeding of 6468 +/- 3824 kJ/d above weight-maintenance requirements, leading to a 2.3 +/- 1.2-kg gain. The 10,975 +/- 3774 kJ excess energy intake on day 7 of ad libitum intake caused a 1205 +/- 920 kJ/d increase in 24EE (delta 24EE = 0.17 x delta intake - 695; r = 0.71, P less than 0.02). Of the excess carbohydrate intake, 74% was oxidized (r = 0.86, P less than 0.001), whereas excess fat intake was not. Carbohydrate and protein stores are regulated whereas excess fat intake is channeled to fat stores.

Energy expenditure of elite female runners measured by respiratory chamber and doubly labeled water.

To determine whether female athletes have unusually low energy requirements as suggested by many food intake studies, energy expenditure (EE) and intake were assessed in nine elite distance runners [26 +/- 3 (SD) yr, 53 +/- 4 kg, 12 +/- 3% body fat, and 66 +/- 4 ml.kg-1.min-1 maximal O2 uptake]. Subjects were admitted to a metabolic ward for 40 h during which 24-h sedentary EE was measured in a respiratory chamber. Free-living EE was then assessed by the doubly labeled water method for the next 6 days while the women recorded all food intake, daily body weight, and training mileage (10 +/- 3 miles/day). Energy intakes estimated from free-living EE (2,826 +/- 312 kcal/day) and body weight changes (-84 +/- 71 g/day) averaged 221 +/- 550 kcal/day in excess of those calculated from food records (2,193 +/- 466 kcal/day). The energy cost of training (1,087 +/- 244 kcal/day) was calculated as the difference between free-living EE and 24-h EE in the respiratory chamber (1,681 +/- 84 kcal/day) corrected for the thermic effect of food of the extra energy intake. These data do not support the hypothesis that training as a distance runner results in metabolic adaptations that lower energy requirements in women.

Ethnic differences in sympathetic nervous system-mediated energy expenditure.

The impact of sympathetic nervous system (SNS) activity on energy expenditure (EE) was evaluated in nondiabetic Caucasian and Pima Indian men while on a weight-maintenance diet using two approaches as follows. 1) The relationship between 24-h EE, measured in a respiratory chamber, and 24-h urinary norepinephrine was studied in 36 Caucasians [32 +/- 8 (SD) yr, 95 +/- 41 kg, 22 +/- 13% fat] and 33 Pimas (29 +/- 6 yr, 103 +/- 28 kg, 30 +/- 9% fat). There was no difference between the two groups in 24-h EE (2,422 vs. 2,523 kcal/24 h) and in urinary norepinephrine (28 vs. 31 micrograms/24 h), even after adjusting for body size and composition. Twenty-four-hour EE correlated significantly with 24-h urinary norepinephrine in Caucasians (r = 0.78, P less than 0.001) but not in Pimas (r = 0.03), independent of fat-free mass (FFM), fat mass, and age. 2) The effect of beta-adrenoceptor blockade with propranolol (120 micrograms/kg FFM bolus and 1.2 micrograms.kg FFM-1.min-1 for 45 min) on the resting metabolic rate (RMR) was evaluated in 36 Caucasians (30 +/- 6 yr, 103 +/- 36 kg, 25 +/- 11% fat) and 32 Pimas (28 +/- 6 yr, 100 +/- 34 kg, 27 +/- 10% fat). The RMR was similar in the two groups (2,052 vs. 1,973 kcal/24 h) even after adjustment for FFM, fat mass, and age and dropped significantly after propranolol infusion in Caucasians (-3.9%, P less than 0.001) but not in Pimas (-0.8%, P = 0.07).(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of a tricyclic antidepressant and opiate antagonist on binge-eating behavior in normoweight bulimic and obese, binge-eating subjects.

A subset of the obese population (25-30%) has been reported to engage in binge eating at least twice weekly (bingers) and to exhibit personality traits and food attitudes similar to those of normoweight bulimic women (bulimics). Tricyclic antidepressants and opiate antagonists effectively suppress binge eating in normoweight bulimics. This 8-wk placebo-controlled, double-blind trial investigated the effect of naltrexone and imipramine on 33 obese bingers and 22 bulimics. Naltrexone (100-150 mg/d) produced a significant reduction in binge duration in bulimics (36 +/- 16%, median +/- SIQR; P = 0.02) whereas imipramine significantly reduced binge duration in obese bingers (88 +/- 31%; P = 0.02). A strong placebo effect was observed in obese bingers and, although a reduction in binge frequency occurred with both naltrexone and imipramine, it was not significantly different from the effect in placebo control subjects. We conclude that naltrexone and imipramine may be useful agents in the treatment of binge eating.

Effect of endurance training on sedentary energy expenditure measured in a respiratory chamber.

The effect of endurance training on 24-h energy expenditure (EE), basal metabolic rate (BMR), sleeping metabolic rate (SMR), and the thermic effect of food (TEF) was assessed in a respiratory chamber where only spontaneous physical activity (SPA) was allowed. Results from 20 highly trained male endurance athletes (25 +/- 5 yr, 178 +/- 7 cm, 70 +/- 8 kg body wt, 64 +/- 7 kg fat-free mass) were compared with those of 43 untrained males who were matched for age (28 +/- 6 yr), height (175 +/- 5 cm), weight (73 +/- 13 kg), and fat-free mass (62 +/- 8 kg). Subjects were admitted to a metabolic ward, fed a weight-maintenance diet, and refrained from physical activity for at least 2 days before measurements. No significant differences were found with respect to 24-h EE (2,126 +/- 186 vs. 2,154 +/- 245 kcal), BMR (1,808 +/- 342 vs. 1,709 +/- 329 kcal), SMR (1,523 +/- 120 vs. 1,555 +/- 188 kcal), or TEF (24.9 +/- 9.2 vs. 21.3 +/- 6.7% of ingested calories; these values included the energy cost of arousal) between trained and untrained subjects, respectively, before or after adjusting for differences in body composition. Neither the 24-h respiratory quotient nor the level of SPA differed between the two groups. No relationship was found between maximal aerobic capacity and metabolic rate adjusted for differences in fat-free mass and fat mass. These results do not support an effect of fitness level on EE measured under sedentary conditions.(ABSTRACT TRUNCATED AT 250 WORDS)