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Biomedical subjects

M Krotkiewski

Publications and source records attributed to M Krotkiewski.

At least 19 recordsLinked to original sources

Role of muscle morphology in the development of insulin resistance and metabolic syndrome.

Type IIB muscle fibres are among the most insulin-insensitive muscle fibres and are not adapted to oxidation of fat during muscle work. The first characteristic of this type of muscle fibre most probably reflects or contributes to further development of insulin resistance contribute to further perpetuation of obesity and to the channeling of excess free fatty acids to the liver followed by secondary deterioration of its function. The impaired functioning of the liver is epitomized, among other changes, by impairment of insulin extraction. The increasing hyperinsulinaemia is followed by inhibition of synthesis of specific proteins such as carrier proteins for transporting testosterone (sex hormone binding globulin, SHBG). This results in an increased free testosterone concentration which induces androgenization in women and may further increase insulin insensitivity in abdominal obesity in women. The poor capillarization and changed muscle morphology in spite of great interindividual variety is observed in several pathological conditions characterised by insulin sensitivity (stroke, PCO, hypertension, diabetes, obesity). It is suggested that, in addition to the previous concept of the main role of intraabdominal adipose tissue, even muscles and liver are also important organs contributing to the pathogenesis and development of the metabolic syndrome.

Exercise

Muscle fiber composition and capillary density in women and men with NIDDM.

OBJECTIVE: To determine whether muscle fiber composition and capillary density differed between diabetic and nondiabetic subjects. RESEARCH DESIGN AND METHODS: Muscle fiber composition and capillary density were determined in biopsies from women and men with non-insulin-dependent diabetes mellitus (NIDDM) and compared with those of control subjects matched for gender, age, obesity, and the waist-to-hip ratio, which are all factors known to influence muscle morphology. RESULTS: Patients with NIDDM, as well as control subjects with abdominal obesity and insulin resistance, showed the same abnormalities in muscle morphology, namely, a low percentage of type I fibers, elevated type II (particularly type IIB) fibers, and a low capillary density. These changes correlated closely with insulin concentrations in both diabetic and nondiabetic groups. CONCLUSIONS: Recent information suggests that insulin may regulate myosin synthesis in muscle in the direction of the changes observed. Therefore, it is possible that muscle fiber composition abnormalities in insulin-resistant conditions are secondary to hyperinsulinemia. However, the low capillary density, hypothetically, may contribute to insulin resistance.

Biopsy

Effects of acute exercise on insulin and non-insulin-dependent glucose uptake in normal and moderately obese women.

OBJECTIVES: To investigate the effectiveness of exercise on the regulation of insulin sensitivity. METHODS: Eleven premenopausal women, with body fat mass from the normal range to moderate obesity, were examined with glucose clamp at 10 mmol/L glucose concentration to determine insulin-dependent and non-insulin-dependent (after somatostatin inhibition of endogenous insulin production) glucose uptake (= IDGU and NIDGU respectively) before and 24 hrs after a glycogen-decreasing exercise. RESULTS: IDGU, but not NIDGU, increased after exercise. The degree of increase of IDGU after exercise showed negative correlations with body mass index (borderline, significance), the waist to hip circumference ratio, fasting free testosterone and free fatty acid concentrations, as well as diastolic blood pressure (borderline significance), and a positive relationship to sex hormone binding globulin concentration and IDGU before exercise. CONCLUSION: It is concluded that only IDGU contributes to the augmentation of insulin sensitivity after a glycogen-decreasing exercise in women. Additionally, the increase of IDGU is less in abdominal obesity, and negatively dependent on free fatty acid concentrations, hyperandrogenism and hyperinsulinaemia, all putative pathogenetic factors for insulin resistance.

Adult

Uptake of glucose carbon in muscle glycogen and adipose tissue triglycerides in vivo in humans.

Glucose disposal into muscle glycogen has previously been directly studied after intravenous, but not after physiological, oral administration. In this study 100 g glucose, containing 50 microCi [U-14C]glucose, were taken orally by premenopausal women in the overnight fasting state or after a carbohydrate-rich meal. After 4 h, biopsies were taken from the vastus lateralis muscle and abdominal and femoral subcutaneous adipose tissue for determinations of label in isolated glycogen and triglycerides, respectively. Uptake of administered glucose carbon in muscle glycogen was estimated to be approximately 20 g in the fasting and approximately 9 g in the carbohydrate-fed groups, respectively. Total uptake in adipose tissue triglycerides was approximately 2 g. Glucose carbon uptake in muscle glycogen correlated positively with glucose infusion rates during euglycemic hyperinsulinemic glucose clamps, glycogen synthase activity in vitro, and type I muscle fiber distribution and fiber area. Negative correlations were found between glucose uptake in adipose tissue triglycerides, type II fiber distribution and fiber area, as well as the waist-to-hip circumference ratio and degree of obesity. It was concluded that muscle glycogen is probably not a major pathway for disposal of oral glucose carbon in the sedentary condition.

Adipose Tissue

Androgen treatment of middle-aged, obese men: effects on metabolism, muscle and adipose tissues.

OBJECTIVES: This pilot investigation was conducted to explore the relationship between androgens and glucose tolerance in obese men and to select an optimal mode for androgen treatment. METHODS: For exploratory purposes, testosterone (T) or dihydrotestosterone (DHT) were given in different doses and preparations for different periods of time to obese, middle-aged men. The administration forms were selected in order to by-pass the liver. In the first two studies T was given as a single intramuscular injection of 250 or 500 mg and the results evaluated after 1 week. In two subsequent studies testosterone was administered in moderate doses either as oral T undecanoate or a T and DHT in preparations applied on the skin for transdermal absorption for 6 weeks and 3 months respectively. Before and after treatment the following examinations were performed: glucose tolerance tests with insulin determinations or euglycemic clamps at submaximal insulin levels. Anthropometric measurements including the waist/hip circumference ratio and estimations of body fat and lean body mass (from measurements of whole body potassium content) were performed. Plasma triglyceride and cholesterol concentrations, liver function tests and blood pressure were followed. Physical examination including the prostate was performed before and after study. Muscle function, glycogen synthase and morphology were examined in the 3-month study. RESULTS: Administration of T was followed by moderate increases of circulating T concentrations in all studies, except after injection of 500 mg, where large increases were seen. Follicle stimulating hormone and luteinizing hormone levels decreased consistently. Injection of 500 mg T resulted in a decreased glucose tolerance. In the other treatment groups, plasma insulin decreased or glucose disappearance rate increased in clamp measurements, suggesting improved insulin sensitivity. This was most pronounced in men with relative hypogonadism from the outset. In the study of 3 months duration, a decrease in the waist/hip ratio, without a change in body fat mass, was also seen. Plasma lipids, liver function tests and blood pressure did not change. Muscle strength, the fractional velocity of glycogen synthase as well as the percentage and diameter of type IIB fibres increased after T treatment. No adverse effects were seen. 17 -beta oestradiol concentrations were unaltered and DHT administration was less effective than T, suggesting that T rather than derivatives of this hormone was mainly responsible for the effects observed. CONCLUSION: The results suggest that T administration to middle-aged, obese man may have beneficial effects.

Adipose Tissue

Hemorheological disturbances, metabolic parameters and blood pressure in different types of obesity.

Body fat distribution characterized by a high waist/hip ratio (WHR) has been described as a risk factor in the incidence of cardiovascular diseases and associated mortality. Hemorheological changes have been shown to accompany several risk factors. Gynoid and android obese women were compared in the present study with respect to hemorheological and metabolic variables and blood pressure. The android obese women had a significantly higher hematocrit and red blood cell count and showed higher blood viscosity at both high and low shear rates than women with the gynoid obesity type. Blood pressure was also higher in the android group. No significant differences were shown in concentration of cholesterol or triglycerides in serum nor in the microrheological properties of the red blood cells. The filterability index, which mirrors the number of rigid erythrocytes in the blood, was found to correlate with the plasma insulin concentration (r = 0.78, P less than 0.05) in the android but not in the gynoid obese women. It is concluded that the pathological changes in blood rheology observed in the android obese women may contribute to the high rate of cardiovascular events and associated mortality reported in this type of obesity.

Adipose Tissue

Effects of a sodium-potassium ion-exchanging seaweed preparation in mild hypertension.

A nonpharmacological approach in the treatment of mild hypertension is often advocated. In an attempt to decrease sodium and increase potassium intake, sixty-two middle-aged patients with mild hypertension were given a potassium loaded ion-exchanging sodium-adsorbing potassium-releasing seaweed preparation (seaweed fiber, SF). The mean blood pressure (MBP), evaluated in a double-blind crossover manner with four weeks familiarization and wash-out periods, showed a significant decrease after four weeks on 12 and 24 g/day SF but not on 6 g/day or placebo treatment. Systolic blood pressure during submaximal exercise decreased on all three SF doses. The decrease in MBP appeared to be significantly higher in sodium-sensitive (11.2 mm Hg, P less than .001) than in sodium-insensitive (5.7 mm Hg, P less than .05) patients and was in salt-sensitive patients significantly correlated to the increase in plasma renin activity (PRA). The urinary sodium excretion decreased, the urinary potassium increased and the sodium/potassium urinary excretion ratio decreased, indicating that the decrease of MBP was dependent on the decreased intestinal absorption of sodium and increased absorption of potassium released from the seaweed preparation. A sodium-potassium ion-exchanging seaweed preparation is an effective means of decreasing sodium and increasing potassium intake, and may be used for antihypertensive treatment in mild hypertension.

Adult

The effects of exercise, training on body composition and metabolism in men and women.

In order to examine whether there are sex-differences in the response of energy balance to physical training slightly obese men and women participated in the same 3 months physical training program with the same individual relative intensity. The men became somewhat lighter (-2 kg) and leaner (-2.9 kg body fat) and showed decreases in sum of insulin and sum of C-peptide values during an oral glucose tolerance test as well as cholesterol values. The women showed decrease of 2.6 kg body fat, and also increased lean body mass (1.9 kg) and similar metabolic changes. The women had, however, a larger body fat mass at the outset. When women with similar body fat mass as that of men were analysed separately, no change in body weight or body fat had occurred, and the metabolic adaptations were less pronounced. No compensatory increase of energy intake could be discovered in any of the groups, the most obese women actually showed a decrease. Taken together with previous information these results suggest that men, like male rats, become leaner during physical training due to a lack of energy intake compensation. Women with similar body fat mass, however, like female rats, may react with such a compensation, causing a protection of their body fat. Women usually have more body fat than men, however. Obese women in this study showed a decrease of body fat.

Adult

Abdominal obesity is associated with an impaired fibrinolytic activity and elevated plasminogen activator inhibitor-1.

Recent epidemiologic studies have shown that abdominal obesity, characterized by a high waist to hip circumference ratio (WHR), is associated with increased cardiovascular morbidity and mortality. The present study examines components of the fibrinolytic system in obese and lean middle-aged women with a high and low WHR. Ten women in each group were carefully matched with respect to age, body weight, lean body mass, and body fat. Fibrinogen and endothelial type of plasminogen activator inhibitor -1 (PAI-1) were significantly elevated in the obese women with a high WHR compared with the obese women with a low WHR or with both groups of lean women. In addition, obese women with a high WHR exhibited a greater metabolic risk profile (elevated glucose, insulin, and triglyceride levels). When all subjects were pooled for the analyses, both fibrinogen and PAI-1 levels correlated positively with glucose and insulin levels. PAI-1 was also negatively related to degree of insulin sensitivity measured with the euglycemic clamp technique. In the obese groups, WHR but not body mass index (BMI), correlated with PAI-1 levels. No such correlations were seen in the lean groups. In conclusion, the data show that a high WHR in obese, but not lean middle-aged women, is associated with an impaired fibrinolytic activity. This perturbation becomes enhanced when it is associated with hyperinsulinemia and insulin resistance, which is a typical feature of abdominal obesity.

Cardiovascular Diseases

Increased muscle dynamic endurance associated with weight reduction on a very-low-calorie diet.

To assess muscle function after a period of negative energy balance, 32 obese women were placed on a 544-kcal/d, high-protein diet for 4 wk. Weight loss was associated with a decrease in the waist-to-hip-circumference ratio (WHR) and significantly higher emptying of abdominal than gluteal fat cells. The low-calorie regimen was associated with a significant increase in isokinetic muscle endurance, a decrease in glycogen concentration, and an increase in glycogen synthase (GS) activity and its fractional velocity (FV). The GS activity and its FV were negatively correlated with the WHR before treatment whereas their subsequent increase was correlated with the decrease in WHR. Dietary treatment produced a decrease in the isokinetic muscle strength, which was correlated with the reduction in lean body mass. The improvement in dynamic endurance observed after energy restriction parallels not only the increase in GS activity in muscle but also the decrease in glycogen stores and glucose oxidation, and most probably depends on the increased utilization of fatty acids.

Adipose Tissue

Increased insulin resistance and fat cell lipolysis in obese but not lean women with a high waist/hip ratio.

Increased lipolysis in abdominal adipocytes has been suggested to be of importance for the insulin resistance typical for abdominal obesity. In order to differentiate between fat distribution, measured as waist/hip ratio (WHR), and amount of body fat, glucose disposal during a euglycaemic clamp as well as lipolysis in isolated cells from abdominal and gluteo-femoral regions were studied in 20 obese and 20 lean postmenopausal women with a high (n = 10) and low (n = 10) WHR, respectively. The lipolytic response was increased in cells from obese women irrespective of region. Furthermore, lipolysis was enhanced in abdominal compared with the gluteo-femoral cells in obese women with a high WHR. Fasting blood glucose and insulin were increased in both groups of obese women while the degree of insulin resistance was most pronounced in the obese women with a high WHR. It is concluded that increased body fat is associated with both insulin resistance and increased lipolysis, and that this relationship is stronger in the presence of a high WHR. A high WHR may increase the expression of obesity as a risk for insulin resistance and this may be mediated through an increased lipolytic rate.

Adipose Tissue

Glucose tolerance and hyperinsulinaemia in obese women: role of adipose tissue distribution, muscle fibre characteristics and androgens.

The separate independent statistical contribution of abdominal distribution of fat, hyperandrogenicity and muscle morphology to glucose intolerance and hyperinsulinaemia was analysed in 88 obese women. In univariate analyses the waist/hip circumference ratio (WHR), body fat and lean body mass were all positively associated, and SHBG levels were negatively associated with insulin and glucose values. Muscle fibre areas were positively correlated with insulin but not with glucose concentrations. Adjustment for other variables did not remove the positive association between WHR and fasting insulin and glucose concentrations. SHBG, free testosterone and type IIb fibre areas were, however, significant confounding factors in the relationship between WHR and summed insulin and glucose concentrations. We conclude that fat distribution in obese women is associated with fasting hyperglycaemia and hyperinsulinaemia, independently of androgens and muscle fibre morphology, but that reduced SHBG concentrations and increased type IIb fibre areas may partly explain increased glucose and insulin responses to an oral glucose load in abdominally obese women.

Abdomen

Importance of obesity for the metabolic abnormalities associated with an abdominal fat distribution.

Obese people with a high waist/hip ratio (W/H ratio) have an increased risk for cardiovascular disease. The present study was designed to separately analyze the importance of obesity and the regional fat distribution for the metabolic risk factors. Blood pressure, glucose tolerance, insulin, and plasma lipid levels were studied in lean and obese postmenopausal women with a high or low W/H ratio. The individuals within each group were carefully matched for age, lean body mass, and body fat. The risk factors associated with a high W/H ratio (elevated blood pressure, blood lipids, and glucose levels) were found in the obese but not in the lean women. Furthermore, lean women with a high W/H ratio tended to have a lower metabolic risk factor profile than obese women with a low W/H ratio. These findings document the importance of obesity in expressing the metabolic risk factors for cardiovascular disease associated with a high W/H ratio.

Abdomen

Effect of isoproterenol on the plasma C-peptide and insulin levels in humans.

There are conflicting reports on the effect of stimulation of the beta-adrenergic receptors on insulin removal by the liver. It was, therefore, the aim of the present study to clarify that problem. Four experiments have been carried out on a group of 8 healthy female volunteers: (1) isoproterenol was infused intravenously, (2) glucose was infused intravenously, (3) isoproterenol was infused with glucose, and (4) infusion of isoproterenol and glucose was preceded by administration of propranolol (the beta-adrenergic blocking agent). The concentration of C-peptide and insulin was determined in plasma from the antecubital vein. It has been found that stimulation of the beta-adrenergic receptors with isoproterenol reduces insulin removal by the human liver. This effect of isoproterenol is prevented by blockade of the beta-adrenergic receptors with propranolol.

Adrenergic beta-Agonists

Regional distribution of muscle and fat mass in men--new insight into the risk of abdominal obesity using computed tomography.

We studied 24 healthy men (25-50 years old) covering a wide range of fatness (body mass index range: 21-34 kg/m2) and fat distribution (waist/hip range: 0.75-1.06). Computed tomography scans were taken at five levels (thigh, hip, waist, arm, and liver) from which fat, muscle and bone areas were calculated. Both waist/hip and BMI were correlated with fat areas in the thigh, arm and waist scans. BMI showed stronger correlations with peripheral fat areas, whereas waist/hip showed stronger correlations with fat areas in the waist scan (particularly with visceral fat area: r = 0.88, P less than 0.001). BMI was correlated with muscle and bone areas in the thigh scan. In multiple regression BMI was, independently of waist/hip and age, positively correlated with fat areas in the arm, thigh, and waist (not with visceral fat) and muscle and bone areas in the thigh. Waist/hip was independently of BMI and age correlated with fat areas in the arm and waist, including visceral fat area (but not with fat areas in the thigh). Moreover, waist/hip showed an independent negative correlation with muscle area in the thigh, muscle endurance and physical activity. Serum triglycerides, plasma insulin, glucose, uric acid and diastolic and systolic blood pressure were associated with visceral fat area but also to anthropometric indicators of abdominal fat distribution (especially waist/hip ratio). Liver attenuation, but not the liver/spleen attenuation ratio, was associated with some liver enzymes and BMI but not with waist/hip or metabolic parameters. We conclude that a higher BMI is associated with increased central and peripheral fat stores (but not visceral fat) and increased thigh muscle whereas waist/hip is primarily associated with increased central fat stores (noteably with visceral fat), decreased thigh muscle and reduced physical fitness. It is suggested that physical training might be an important element in the treatment of abdominal obesity in men.

Abdomen

Can body fat patterning be changed?

Short- and long-term weight reduction programmes both resulted in a significant decrease in the waist/hip ratio (WHR) among obese premenopausal women. In matched groups of women with gynoid and android obesity, the latter demonstrated a greater decrease in WHR after 1 year's weight reduction and, at the same level of body weight loss, a consistently lower decrease in the lean body mass. Gluteal fat cells were found to empty at a slower rate than those in the abdominal region, particularly in gynoid obesity. After 1 year's weight reduction, the decrease in WHR correlated significantly with decreases in body weight, blood pressure and metabolic variables. Six months' physical training with and without reduction of body weight resulted in a significant decrease in WHR, while one-leg exercise caused a local decrease in the circumference of the trained leg. Reduction of flatulence in obese men was also found to be associated with decreased WHR.

Adipose Tissue