Tore Scherstén

Carbohydrate and lipid metabolism in middle-aged, physically well-trained men☆

Abstract Body composition, maximal oxygen uptake, plasma lipids, glucose and lipid tolerance, and plasma insulin were examined in middle-aged, physically well-trained men in comparison with randomly selected men of the same age. The well-trained men were characterized by a small adipose tissue consisting of small fat cells, and probably by an increased muscle mass. They had an elevated maximal oxygen uptake. Fasting plasma lipids were low. Assimilation of 100 g glucose perorally was very rapid and occurred while insulin concentrations in plasma were much lower than in controls. Fasting plasma insulin values were also low. Intravenous lipid tolerance test showed a rapid removal rate of triglycerides. Analyses of glucose metabolism in vitro in muscle biopsies from these men showed an increased activity in several metabolic pathways. Succinic oxidase activity, as a marker of aerobic capacity as well as glycogen contents, was also increased. These results indicate that physical training is a potent factor for regulation of plasma insulin levels. It was suggested that qualitative and quatitative changes in muscle capacity to metabolize glucose are in some way involved in this regulation.

Intermittent claudication--surgical reconstruction or physical training? A prospective randomized trial of treatment efficiency.

This study reports the initial evaluation of treatment efficiency in 75 patients with intermittent claudication who were randomized to three treatment groups: 1) reconstructive surgery, 2) recon structive surgery with subsequent physical training, and 3) physical training alone. Before treatment, there were no statistically significant differences between the groups in age, sex, smoking habits, symptom duration of claudication, ankle-arm blood pressure quotient (ankle-index), maximal plethysmographic calf blood flow, symptom-free and maximal walking distance, the history of other atherosclerotic manifestations or in the medical treatment. The walking performance was improved in all three groups at follow-up 13 ± 0.5 months after randomization. Surgery was most effective, but the addition of training to surgery improved the symptom-free walking distance even further. In pooled observations of the three groups, age, symptom duration, and a history of myocardial ischemic disease correlated negatively with walking performance after treatment. In the operated group, the duration of claudication and a history of myocardial ischemic disease correlated negatively with the walking performance. This was not the case when patients were censored if limited by other symptoms than intermittent claudication after treatment. In the trained group, the duration of claudication correlated negatively to symptom-free and maximal walking distance. Ankle-index and maximal plethysmographic calf blood flow after treatment and the change of these variables with treatment correlated positively with both symptom-free and maximal walking distance when results were pooled for all patients. Although this mainly was a consequence of the improved blood flow after surgery, the change of maximal plethysmographic calf blood flow also correlated with symptom-free but not with maximal walking distance in the trained group. The results demonstrate that, compared with physical training alone, operation alone or in combination with subsequent training are superior treatment modalities in patients with intermittent claudication.

Skeletal muscle metabolism in patients with malignant tumor.

Abstract Skeletal muscle biopsies were taken from 43 cancer patients and 55 matched, presumably metabolically healthy controls for determinations of enzyme activities, capacity of glucose assimilation and metabolism and the incorporation rate of leucine into proteins. In muscle tissue from cancer patients the activities of the lysosomal enzymes, cathepsin-D and β-glucuronidase, were increased. Acid phosphatase activity was the same as in muscle tissue from the controls. The activities of hexokinase, phosphofructokinase, lactate dehydrogenase, and cytochrome-c-oxidase were significantly decreased. This decrease was accompanied by a decreased incorporation rate of glucose-carbon into glycogen, lactate and CO 2 . The incorporation rate of leucine into proteins was significantly decreased in cancer patients and the fractional degradation rate of proteins was increased. Amino acids caused the same degree of stimulation on the leucine incorporation rate into proteins as in the controls. The RNA concentration was unchanged in muscles from the cancer patients. The results suggest that malignant tumors provoke specific alterations of the skeletal muscle metabolism of the host. The rate of protein biosynthesis seems to be decreased together with an increased degradation rate. The capacity for glucose assimilation and metabolism is decreased indicating a disturbed energy regulation in the muscles of cancer patients.

Metabolic Activity of Skeletal Muscle in Patients with Peripheral Arterial Insufficiency

Abstract. 18 patients with intermittent claudication were studied to find some explanation for the beneficial effect of physical training on their symptoms. The patients were randomly allocated to a training group and a placebo‐treated control group. The effect of treatment on serum lipids, muscle lipids and glycogen, walking tolerance, calf blood flow, muscle succinic oxidase activity and the in vitro incorporation rate of glucose‐carbon into various metabolites were studied.

Glucose turnover, gluconeogenesis from glycerol, and estimation of net glucose cycling in cancer patients

A double isotope method was used in patients with progressive malignancy and in control patients to measure: glucose turnover, conversion rate of carbon skeleton of glycerol into glucose, and the interorgan cycling of glucose carbons (Cori‐cycle plus alanine‐glucose cycle). [U‐14Clglycerol and [6‐3H]glucose were given intravenously as a single dose injection. The time course of the specific radioactivities of [6‐3H] and [U‐14C]glucose was followed in blood. The pool size and the turnover rate of glucose were increased in the cancer group as compared with the control patients. The net recycling of glucose carbons was not increased in the cancer group, despite the increased turnover of glucose. The alterations in the metabolism of glucose did not correlate with the plasma levels of insulin or thyroid hormones (T4, T3, rT3) neither in the entire cancer group nor in those cancer patients who were repeatedly investigated at different intervals of time. The turnover rate of glucose in the cancer patients correlated inversely to their body weight index. The gluconeogenesis rate, given as the fractional conversion rate of the injected radioactive dose of [14C]glycerol, or as mol glucose · kg body weight−1 · day−1, was increased in the cancer group, but still contributed only 3% of the glucose turnover rate in both cancer and control patients. We conclude that an increased gluconeogenesis from glycerol is not significant in terms of energy expenditure in patients with progressive malignancy, as has previously been concluded for the gluconeogenesis from alanine.15 It seems that increased turnover of glucose may contribute to inappropriately high energy expenditure in cancer patients.

Chronic lower limb ischaemia. A prospective randomised controlled study comparing the 1-year results of vascular surgery and percutaneous transluminal angioplasty (PTA)

In a prospective randomised study, performed over a 6-year period, 102 patients with severe lower limb ischaemia or claudication resistant to exercise training were randomised either to percutaneous transluminal angioplasty (PTA) or vascular surgery. Only patients who could be treated by both methods were included, constituting only 5% of the total number of patients treated during this period. The two groups were similar regarding age, severity of symptoms and diabetes. The immediate and 1-year results showed similar success and complication rates. There was, however, a significantly shorter hospital stay for patients treated with PTA. Due to early complications and initial failures PTA should, however, only be used in institutions where vascular surgical facilities are available since PTA demands access to such treatment.

A comparative study of the influence of malignant tumor on host metabolism in mice and man. Evaluation of an experimental model.

Metabolic alterations in skeletal muscles and liver tissue from cancer patients were compared with corresponding alterations in mice (C‐57) with sarcoma (MCG‐101). In tumor‐bearing man and mice similar changes in enzyme activities and in protein turnover were found. Glycolytic and oxidative enzyme activities were decreased in skeletal muscle tissue. Tumor‐associated increase in lysosomal enzyme activities was found in both species. Leucine was incorporated into skeletal muscle proteins at a lower rate and into hepatic proteins at a higher rate in both species with malignant tumor. In tumor‐bearing mice ribosome profiles from skeletal muscle, heart muscle and liver showed a preponderance of slowly sedimenting units of polyribosomes suggesting that initiation of protein synthesis may be a rate limiting step. The metabolic host reactions in tumor‐bearing mice were similar to those in cancer patients implying that experimental tumors are relevant to use for analysis of mechanisms behind the development of cancer cachexia in man.

Treatment of liver metastases of carcinoid tumors

Abstract. Liver metastases imply a major problem in patients with carcinoid tumors. Patients with localized disease should always undergo resection for cure. Patients with distant metastatic disease can also undergo resection for potential cure or symptom palliation because of the slow growth rate of many carcinoid tumors. In patients with the midgut carcinoid syndrome and bilobar hepatic disease we have performed primary surgery to relieve such symptoms as intestinal obstruction and ischemia, followed by successive embolizations of the hepatic arteries to reduce functional tumor burden in the liver. For optimal palliation, all patients with residual tumor were treated by octreotide. In a consecutive series of 64 patients with the midgut carcinoid syndrome we thus attained a 5-year survival rate of 70%. Fourteen of the patients underwent intentionally curative surgery (e.g., primary surgery followed by liver surgery). Of these patients, none died from their tumor disease during the period of study. The value of adjunctive interferon therapy is currently under evaluation.

Metabolic Activity in Human Skeletal Muscle Effect of Peripheral Arterial Insufficiency

Abstract Succinic oxidase activity and the incorporation rates of glucose‐carbon into glycogen, lipids, lactate and carbon‐dioxide were studied in vitro in samples of skeletal muscle taken from patients with peripheral arterial insufficiency.

Capillary supply and muscle fibre types in patients with intermittent claudication: relationships between morphology and metabolism.

There have been previous reports on an increased oxidative capacity in muscle tissue from the diseased legs of patients with intermittent claudication. The present study was designed to correlate metabolic and morphological data and to investigate whether the metabolic adaptive changes in muscle tissue of claudicating legs were also reflected in morphological variables such as capillary supply, fibre type distribution, and fibre area. The activity of cytochrome-c-oxidase in gastrocnemius muscle was determined and the insulin and glucose uptakes were measured across the leg in the basal state and 10 min following intravenous administration of 25 g glucose. The finding of a reduced relative number of Type II B fibres and a reduced ratio Type II B/II A fibre area, as well as an increased capillary supply to Type II A, indicated that the most extensive morphologic changes in muscle tissue of claudicating legs had occurred in Type II fibres. The increased number of capillaries in contact with Type II A fibres in muscle tissue from claudicating legs, compared with muscle tissue from control legs, suggested that the most apparent metabolic changes occurred in this fibre type in the adaptation process of these patients. The more pronounced morphologic and metabolic changes in Type II fibres suggest that these fibres are more intensely activated than Type I fibres during physical activity in claudicating legs. The insulin uptake correlated positively with the number of capillaries per fibre, suggesting that the endothelial surface area is one of the determining factors for insulin uptake. The percentage of Type II B fibres reflected to a certain extent the metabolic adaptation in muscle tissue.