Energy expenditure and substrate metabolism were investigated in 10 patients with alcoholic liver cirrhosis (EtOH-Ci) and 10 healthy controls (C). Resting metabolic rate (RMR) varied from 1,269 to 2,467 kcal/day in C and from 1,228 to 2,098 kcal/day in EtOH-Ci. RMR was significantly related to fat-free mass (FFM) in both groups, but EtOH-Ci decreased FFM and increased RMR when expressed per kilogram FFM (+33%). Glucose intolerance, hyperinsulinemia, and a decreased C-peptide-to-insulin ratio were observed in EtOH-Ci after a test meal. Concomitantly, nonoxidative glucose metabolism was reduced in association with normal increases in glucose oxidation. EtOH-Ci reduced insulin sensitivity (-59%) and maximal insulin-dependent glucose disposal (-40%) during a sequential two-step glucose clamp protocol (phase 1: 1 mU.kg body wt-1.min-1 insulin infusion rate + euglycemia; phase 2: 4 mU.kg body wt-1.min-1 insulin infusion rate + 165 mg/dl plasma glucose concentration). This was explained by reduced glucose storage (-99%, -51%) in association with normal responses in glucose oxidation rate, plasma lactate concentration, lipid oxidation rate, and rate of lipogenesis. Defective glucose storage was independent of reduced FFM. EtOH-Ci increased glucose-induced thermogenesis by 57%. We conclude that increased resting metabolic rate, enhanced thermogenesis, defective glucose storage, and normal glucose oxidation together result in increased energy needs and favor negative energy balance in patients with alcoholic cirrhosis.

The apoprotein composition of the main lipoprotein fractions (VLDL, LDL‐1, LDL‐2 and HDL) was studied initially in 15 patients with Broad‐β disease. Analytical isoelectric focusing of urea‐soluble apo‐VLDL and apo LDL‐1 demonstrated a variant pattern of the polymorphic Apoprotein E with a deficient Apo E‐III band in all patients. The Apo E‐III deficiency pattern was seen in only six out of 304 hyperlipidaemic controls. These six Apo E‐III deficient controls had characteristic signs of Broad+ disease, and thus represented patients not previously recognized as having the disorder. The Apo E focusing patterns were constant on repeated examinations and were stable under different metabolic conditions. The data show that Apo E‐III deficiency in VLDL is a specific qualitative marker for Broad‐β disease, allowing an unequivocal diagnosis that had not been possible previously. Indirect evidence suggests that Apo E‐III deficiency is the basic lipoprotein abnormality underlying the familial dyslipoproteinaemia.

In contrast to prevention, the therapy of manifest osteoporosis remains a clinically significant problem. So far all therapeutic attempts have yielded unsatisfying results. For this reason we have tried to achieve a positive bone balance by sequential stimulation and inhibition of the osseous metabolism. The therapy consisted of six 14-day courses with 400 units (1-38)hPTH per day and, in addition, starting with the 2nd week of PTH therapy, EHDP 5 mg per kg body weight per day for a total of 2 weeks. Already the initial therapeutic course resulted in a stimulation of decreased bone metabolism which could be documented by an increase in the calcium-47 accretion rate (six patients). An increase of the alkaline phosphatase could be noted (four patients); this, however, did not correlate with the calcium accretion. A positive calcium balance could, nonetheless, only be attained in four of eight patients within this period, while neither the alkaline phosphatase nor the kinetics would allow a prediction of this effect. Changes of the balance coincided with equal changes in the net calcium absorption. The urinary calcium excretion increased temporarily during the therapeutic phase. We were not able to detect an influence on the vitamin D metabolites. Histomorphometric studies did not demonstrate an increase in bone mass in the iliac creast after six therapeutic courses. Nevertheless, progressive deformations of vertebral bodies did not occur. We conclude that already after 2 weeks this therapeutic concept can lead to a stimulation of bone metabolism.

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Malnutrition is frequently seen in patients with inflammatory bowel disease, and parenteral or enteral nutrition is considered essential in this patient group. However, many patients with Crohn's disease have difficulties in gaining weight in response to overfeeding, suggesting reduced energy retention. Substrate utilization and nutrient balances as well as changes in body composition were followed in 10 patients with Crohn's disease immediately in the course of remission on low-dose steroid treatment, during an eight-day period of continuous enteral nutrition at constant (protocol 1:1.5-fold basal energy expenditure) and increasing (protocol 2:0.5- to 2.0-fold basal energy expenditure) nutrient supply. Energy, substrate, and nitrogen balances all became positive in response to overfeeding. However, fat was predominantly oxidized at an infusion rate of 1.2 g/kg body wt/day, whereas carbohydrates and proteins were effectively stored. A positive energy balance was reached at an energy infusion rate exceeding 31 kcal/kg body wt/day and corresponding substrate supplies of 1.6, 1.7, and 1.1 g/kg body wt/day for carbohydrates, fat, and protein, respectively. Nitrogen balance normalized at a supply of 0.14 g/kg body wt/day, which also reduced myofibrillar protein breakdown. Considering the relative contributions made by these nutrients in the diets, an accumulation of carbohydrates and protein but a depletion in fat became evident from nutrient balances. In fact, body weight increased by 0.12 kg/day, which was explained by an increased extracellular (+0.18 kg/day) and body cell mass (+0.04 kg/day) at reduced fat mass (-0.10 kg/day). Concomitantly, plasma T3 and insulin secretion both increased, whereas sympathetic nervous system activity decreased with overfeeding. This is contrary to data observed in healthy subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

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Chenodeoxycholic acid (CDCA) was administered for an average of 15 months to 14 patients with gall-stones. The gall-stones were radiolucent in all but one instance (solitary calcified stone). Stones dissolved completely after 12 and 15 months of therapy, respectively, in two patients, while in four the size of the stones diminished. No change occurred in the remaining patients. In five patients multiple stones dissolved, while in one a radiolucent solitary stone dissolved. In one patient, with a negative cholecystogram for a time before being treated with CDCA, the gall-bladder perforated while on treatment. CDCA was well tolerated by all patients: upper abdominal discomfort disappeared during CDCA treatment in two patients and improved in nine. Only side-effect was occasional mild diarrhoea in five patients. Bile was analysed in seven patients, supersaturation with cholesterol being found in five. Biliary lipid composition became normal during CDCA treatment in these five patients. Serum triglyceride levels fell during CDCA administration in ten of eleven patients in which serum measurements were made; the greatest fall occurred in the five patients with hypertriglyceridaemia. The fall in triglyceride levels was associated with a diminution of the pre-beta-lipo-protein fraction and the chylomicron fraction. No significant change occurred in serum cholesterol levels.

1. Resting energy expenditure and the metabolic responses to adrenaline (infusion rate: 0.03 micrograms min-1 kg-1 fat-free mass for 1 h) were investigated in 25 patients with liver cirrhosis. The patient group was heterogeneous and varied with respect to the aetiology of cirrhosis, the clinical condition (i.e. Child A or B), the nutritional status and the degree of hyperinsulinaemia. 2. When compared with 10 healthy control subjects the basal plasma adrenaline and noradrenaline concentrations were both increased in cirrhosis and remained elevated during adrenaline infusion (+39% and +31%, respectively; P < 0.05). Concomitantly, the peripheral plasma insulin concentration and the molar C-peptide/insulin ratio were increased in liver cirrhosis (+96% and +30%, respectively; P < 0.05). Hyperinsulinaemia was more pronounced in patients with ethanol-induced liver cirrhosis. 3. When expressed per kg fat-free mass, resting energy expenditure was enhanced in liver cirrhosis (+21%; P < 0.05) and was more pronounced (i.e. resting energy expenditures of +35% to +49% above estimated values) in patients with ethanol-induced cirrhosis, at advanced stages of the disease and in association with decreased body cell mass. 4. Infusion of adrenaline increased heart rate, O2 consumption and the plasma concentrations of glucose, lactate, free fatty acids, glycerol and 3-hydroxybutyrate, and similar transient increases and subsequent decreases in the respiratory quotient were observed in both groups. However, the lipolytic, ketogenic and thermic responses were reduced in cirrhotic patients. Reduced metabolic responses were more pronounced in hyperinsulinaemic patients.(ABSTRACT TRUNCATED AT 250 WORDS)