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ABSTRACT: Achievement of good metabolic control in Type 1 diabetes is a difficult task in routine diabetes care. Education-based flexible intensified insulin therapy has the potential to meet the therapeutic targets while limiting the risk for severe hypoglycaemia. We evaluated the metabolic control and the rate of severe hypoglycaemia in real-life clinical practice in a centre using flexible intensified insulin therapy as standard of care since 1990.
Patients followed for Type 1 diabetes (n = 206) or those with other causes of absolute insulin deficiency (n = 17) in our outpatient clinic were analysed in a cross-sectional study. Mean age (± standard deviation) was 48.9 ± 15.7 years, with diabetes duration of 21.4 ± 14.4 years. Outcome measures were HbA(1c) and frequency of severe hypoglycaemia.
Median HbA(1c) was 7.1% (54 mmol/mol) [interquartile range 6.6-7.8 (51-62 mmol/mol)]; a good or acceptable metabolic control with HbA(1c) < 7.0% (53 mmol/mol) or 7.5% (58 mmol/mol) was reached in 43.5 and 64.6% of the patients, respectively. The frequency of severe hypoglycaemic episodes was 15 per 100 patient years: 72.3% of the patients did not experience any such episodes during the past 5 years.
Good or acceptable metabolic control is achievable in the majority of patients with Type 1 diabetes or other causes of absolute insulin deficiency in routine diabetes care while limiting the risk for severe hypoglycaemia.
Diabetic Medicine 05/2011; 28(5):539-42. · 2.90 Impact Factor
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ABSTRACT: To evaluate the effect of metformin on basal and insulin-induced glucose uptake in subcutaneous and visceral preadipocyte-derived adipocytes from obese and non-obese patients, preadipocytes were obtained from subcutaneous and visceral fat depots during abdominal surgery. Differentiation efficiency was evaluated by measurement of intracellular triglyceride accumulation. Preadipocyte-derived adipocytes were treated with metformin (1 mM) for 24 h with or without the addition of insulin (100 nM) for 20 min and glucose uptake was measured. In cells from each donor, intracellular triglyceride accumulation was more abundant in subcutaneous preadipocyte-derived adipocytes than in visceral preadipocyte-derived adipocytes (p < 0.001). Insulin stimulated glucose uptake in subcutaneous preadipocyte-derived adipocytes from both non-obese and obese patients (p < 0.001 vs. basal). In visceral preadipocyte-derived adipocytes, insulin did not increase basal glucose uptake. In subcutaneous preadipocyte-derived adipocytes from non-obese and obese patients, metformin alone increased glucose uptake to 2.7 +/- 0.2 (p < 0.001) and 2.1 +/- 0.1 fold (p < 0.001) respectively. Metformin increased glucose uptake in visceral preadipocyte-derived adipocytes from non-obese (1.7 +/- 0.1 fold vs. basal, p < 0.001) and obese (2.0 +/- 0.2 fold vs. basal, p < 0.001) patients. Combined treatment with metformin and insulin increased glucose uptake in subcutaneous preadipocyte-derived adipocytes from both non-obese and obese patients (p < 0.001 vs. insulin alone). In preadipocyte-derived adipocytes glucose uptake is induced by metformin independent of the fat depot origin of the preadipocytes (subcutaneous or visceral) and the obesity state of the patients (non-obese or obese). In adipocytes, metformin seems to induce glucose uptake independent of insulin suggesting an alternative mechanism of action of this drug.
Diabetes Obesity and Metabolism 04/2010; 12(4):356-9. · 3.38 Impact Factor
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ABSTRACT: To investigate the prevalence and risk factors of perceived diabetes-related discrimination in the workplace and in work-related insurances in persons with diabetes mellitus in Switzerland.
509 insulin-treated diabetic subjects representative of the northwestern Swiss population responded to a self-report questionnaire on perceived diabetes-related discrimination in the workplace and in work-related insurances (salary loss insurance, supplementary occupational plan). Discrimination was defined as being treated differently at least once in relation to diabetes.
The reported rates of different aspects of discrimination in the workplace and in work-related insurances ranged between 5-11% and 4-15% respectively. Risk factors that independently increased the risk of not being hired due to diabetes were the presence of at least two severe hypoglycaemic events/year and relevant diabetic complications (OR 5.6 and OR 2.6 respectively; both<0.05). The presence of at least two severe hypoglycaemic events/year was also associated with an increased risk of losing one's job (OR 6.5, <0.01). Overweight or obesity were related to increased discrimination in work-related insurances (OR for denial 2.1-2.4; OR for reserve 3.9-4.4; all<0.05).
Perceived diabetes-related discrimination in the workplace and by work-related insurances is a common problem. In the light of our findings the introduction of effective non-discrimination legislation for patients with chronic illnesses appears to be desirable.
Swiss medical weekly: official journal of the Swiss Society of Infectious Diseases, the Swiss Society of Internal Medicine, the Swiss Society of Pneumology 03/2009; 139(7-8):103-9. · 1.89 Impact Factor
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ABSTRACT: Intensified insulin therapy has evolved to be the standard treatment of type 1 diabetes. However, it has been reported to increase significantly the risk of hypoglycaemia. We studied the effect of structured group teaching courses in flexible insulin therapy (FIT) on psychological and metabolic parameters in patients with type 1 diabetes.
We prospectively followed 45 type 1 diabetic patients of our outpatient clinic participating in 5 consecutive FIT teaching courses at the University Hospital of Basel. These courses consist of 7 weekly ambulatory evening group sessions. Patients were studied before and 1, 6, and 18 months after the course. Main outcome measures were glycated haemoglobin (HbA1c), severe hypoglycaemic events, quality of life (DQoL), diabetes self-control (IPC-9) and diabetes knowledge (DWT).
Quality of life, self-control and diabetes knowledge improved after the FIT courses (all p<0.001). The frequency of severe hypoglycaemic events decreased ten-fold from 0.33 episodes/6 months at baseline to 0.03 episodes/6 months after 18 months (p<0.05). Baseline HbA1c was 7.2+/-1.1% and decreased in the subgroup with HbA1c > or = 8% from 8.4% to 7.8% (p<0.05).
In an unselected, but relatively well-controlled population of type 1 diabetes, a structured, but not very time consuming FIT teaching programme in the outpatient setting improves psychological well-being and metabolic parameters.
Diabetes research and clinical practice 01/2009; 83(3):327-33. · 2.16 Impact Factor
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ABSTRACT: To determine the changes in adiponectin multimers upon marked weight loss.
Plasma samples were obtained preoperatively and 3, 6, 12 and 24 months after surgery from 12 obese subjects undergoing weight loss-inducing bariatric surgery. Seven non-operated obese subjects served as controls. Plasma levels of adiponectin multimers were determined by protease digestion and Enzyme-Linked ImmunoSorbent Assay (ELISA) detection. In addition, adiponectin multimers were assessed by western blotting.
In patients with weight loss after surgery but not in controls, total adiponectin and high molecular weight (HMW) adiponectin steadily increased during the observation period. Twenty-four months after surgery, the increase in total and HMW adiponectin was 2.2 +/- 0.46 and 1.4 +/- 0.3 microg/ml, respectively. In contrast, plasma concentrations of middle and low molecular weight adiponectin remained unchanged.
The increase in plasma adiponectin levels observed 24 months after bariatric surgery depended on continuous weight loss and was completely attributable to the HMW complex.
Diabetes Obesity and Metabolism 06/2008; 10(12):1266-70. · 3.38 Impact Factor
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ABSTRACT: Restoration of near-euglycaemia by intensive insulin therapy results in decreased serum levels of inflammatory mediators. The authors investigated whether the anti-inflammatory effect of insulin was independent of its glucose-lowering action and if this effect was intact in insulin-resistant women with the polycystic ovary syndrome (PCOS) characterized by low-grade chronic inflammation.
Blood was drawn on the third and sixth days after progestin-induced withdrawal bleeding in 20 young non-diabetic women with PCOS and once between the third and sixth days of the menstrual cycle in 21 age-matched lean healthy control women during a 75-g oral glucose tolerance test (oGTT). Serum insulin, glucose and tumour necrosis factor alpha (TNF-alpha) concentrations were measured after 0, 30, 60, 90 and 120 min.
The increase in insulin and glucose concentrations during the oGTT was significantly more pronounced in patients with PCOS (one patient with impaired fasting glucose, one patient with impaired glucose tolerance, three patients with both) compared with healthy controls. The TNF-alpha serum concentrations decreased in patients with PCOS (mean of both days, P = 0.004). In patients and in controls, there was an inverse correlation between the serum concentrations of insulin and of TNF-alpha during oGTT (for patients, a mean of both days, P = 0.009; for controls, P = 0.047), but not between the serum concentrations of glucose and TNF-alpha.
The decrease in TNF-alpha concentrations during oGTT and the inverse correlation between endogenous hyperinsulinaemia and serum TNF-alpha concentrations suggested an anti-inflammatory effect of moderately-high insulin concentrations. This occurred despite the presence of moderate hyperglycaemia. These findings also demonstrated a preserved responsiveness of inflammatory mediators to insulin in PCOS.
European Journal of Clinical Investigation 01/2007; 36(12):883-9. · 3.02 Impact Factor
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ABSTRACT: In this randomized, double-blind, placebo-controlled study, the effect of sibutramine and cognitive-behavioural weight loss (cognitive-BWL) treatment was assessed in obese subjects with and without subclinical binge eating disorder (sBED).
Seventy-three obese participants were recruited from the community, 29 with and 44 without sBED. Subjects were randomly assigned to a 16-week treatment with either sibutramine or placebo while simultaneously participating in a cognitive-behavioural weight loss treatment.
Intent-to-treat analysis showed moderate weight loss after treatment in all subject groups. Treatment with BWL programs and sibutramine leads to a higher weight loss in all subjects compared with that in patients who had undergone BWL programs alone. Subjects with sBED significantly reduced their binge episodes during treatment, but with no augmenting effect of sibutramine.
Our results yield further evidence that sBED is associated with characteristics comparable with full-syndrome BED, significantly differing from those of obesity alone. These findings call for a systematic assessment of eating behaviour before starting obesity treatment.
Diabetes Obesity and Metabolism 06/2006; 8(3):289-95. · 3.38 Impact Factor
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AJP. 01/2006; 290:1068-1077.
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ABSTRACT: A close link between mood, low-grade inflammation and obesity has been demonstrated even in healthy subjects. We investigated the relationship between changes in physical and psychological symptoms and inflammatory markers during the menstrual cycle both in normal weight and in overweight women.
Eight healthy normal weight (body mass index 21.6 +/- 1.9 kg m(-2)) and seven overweight (body mass index 30 +/- 2.4 kg m(-2)) young women with normal ovarian function and with no premenstrual syndrome were assessed 15 times throughout their menstrual cycle. At each time point fasting blood was drawn and symptoms were recorded using the Freeman Daily Symptom Record.
Independent of weight status, the serum concentrations of highly sensitive C-reactive protein (hs-CRP) and the total scores, in addition to the individual four factors (mood, behaviour, pain and physical symptoms), of the Daily Symptom Record varied significantly during the menstrual cycle (all P < or = 0.04) and paralleled each other. During the menstrual cycle, repeated hs-CRP serum concentrations correlated to the corresponding total symptom score and the factors mood, behaviour and physical symptoms, independent of both weight status and changes in circulating gonadal steroids (all P < or = 0.04). These associations were not observed for tumour necrosis factor-alpha serum levels. The mean hs-CRP concentrations were associated with the mean total symptom score, independent of weight status (r = 0.56, P = 0.04).
Healthy young women showed psychological and physical symptoms during the menstrual cycle which changed in association with alterations in low-grade inflammation and which were independent of body weight or plasma levels of gonadal steroids.
European Journal of Clinical Investigation 01/2006; 36(1):58-64. · 3.02 Impact Factor
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ABSTRACT: The formation of glycogen in the liver of normal volunteers was followed noninvasively with 13C manetic resonance spectroscopy (MRS) under tow different conditions; a) intravenous infusion of [1-13C] glucose under hyperglycemic and hyperinsullinemic clamp conditions, and b) oral Intake of glucose in the form of a bolus. For the intravenous infusion, [1-13C]glucose with an enrichment level of 99% was employed. The C1 signals of α- and β-glucose could be detected in the human liver already after an infusion period of 8 min. However, an increase in the glycogen signal was observed only after a prolonged infusion of about 60 min. Changes in the glycogen signal correlated well with the time course of insulin and glucagon during the measurement. Experiments showed also that liver glycogen formation in man can be followed noninvasively by13C-MRS using nonlabeled glucose or [1-13C]glucose with a low level of enrichment (6.6%). The use of nonlabeled glucose may therefore simplify the quantitation of net liver glycogen synthesis since it can be based directly on changes in the natural abundance 13C MRS glycogen signal, avoiding label dilution through the various metabolic pathways of glucose. The glucose uptake, estimated from the increase in the glycogen signal, was consistent with findings from more complex and invasive studies of glucose uptake in the liver. The average liver glycogen concentration in 12 h overnight fasted volunteers (n = 18) without any special dietary preparation was assessed to be 229 ± 34 mM (minimum = 160 mM; maximum = 274 mM).
Magnetic Resonance in Medicine 11/2005; 29(5):583 - 590. · 2.96 Impact Factor
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ABSTRACT: Dietary factors are important predictors for the risk of diabetes type 2. Increased consumption of fibre-rich foods, fruits and vegetables as well as limited amounts of total and saturated fats are essential elements in the prevention of diabetes type 2. The association between these dietary factors and the appearance of diabetes was not only present in cohort studies but were also major elements in the dietary part of the two large diabetes prevention trials (Finnish Diabetes Prevention Study, Diabetes Prevention Program). There is also strong evidence for a relation between obesity and total fat intake and the incidence of certain types of cancers. There is a significant correlation between total fat intake and the risk of cancer; however, it is much weaker than that of the effect of red meat. Recommendations to decrease red meat intake, particularly processed meat, may decrease the risk of colorectal and prostate cancer and may have beneficial effects on breast cancer as well, although this evidence is less compelling. Overall, recommendations focused on controlling or reducing body weight by regular physical activity and avoidance of excessive energy intake from all sources, particularly from fat and saturated fats, by increasing consumption of fibre-rich carbohydrates, vegetables and fruits are effective in decreasing the risk for type 2 diabetes by more than 50% in high-risk individuals. Similar dietary patterns are likely to diminish the manifestation of certain forms of cancers. These conclusions are in agreement with current recommendations for cancer prevention as propagated by the American Cancer Society.
Physiology & Behavior 01/2005; 83(4):611-5. · 2.87 Impact Factor
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ABSTRACT: Weight loss reduces bone mass and increases the risk of osteoporosis. This study was undertaken to assess changes of bone metabolism following Roux-en-Y gastric bypass (RYGB) and adjustable silicone gastric banding (ASGB) as compared to nonoperated controls of morbidly obese subjects. Fourteen female and 5 male patients with a mean (+/-SEM) age of 44.3 +/- 1.8 years participated in the 24-month prospective study. Nine patients underwent ASGB, 4 patients RYGB operation, and 6 patients were included in the control group. Bone metabolism was assessed by determination of serum parathyroid hormone (PTH), osteocalcin, urinary deoxypyridinoline, and dual energy x-ray absorptiometry (DXA) before, and 6, 12, and 24 months after intervention. The body mass index (BMI) decreased from 41.0 +/- 1.1 to 34.0 +/- 1.4 kg/m2 in the ASGB group (P = .001), from 42.7 +/- 2.2 to 30.5 +/- 2.2 kg/m2 in the RYGB group (P = .006), and remained unchanged in the control group (from 41.2 +/- 1.2 to 41.4 +/- 1.4 kg/m2) after 24 months. Bone mineral content (BMC) showed no significant change in the ASGB group (from 3,079 +/- 140 to 3,064 +/- 129 g) and in the control group (from 2,945 +/- 130 to 2,940 +/- 111 g), whereas it decreased from 2,968 +/- 111 to 2,621 +/- 139 g in the RYGB group (P = .005). The loss in BMC was accompanied by significant increases in urinary deoxypyridinoline (P < .05) and in serum osteocalcin (P < .01) after RYGB, suggesting both, increased bone resorption and increased bone formation. The authors were aware of the fact that the study groups were small and conclusions need to be regarded as preliminary. However, the RYGB operation resulted in enhanced weight loss and significant net loss of bone mass in comparison to ASGB and obese control subjects. Patients losing large amounts of body weight should be monitored regularly regarding prevention of osteoporosis.
Metabolism 07/2004; 53(7):918-21. · 2.66 Impact Factor
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ABSTRACT: Alterations of cell volume induced by changes of extracellular osmolality have been reported to regulate intracellular metabolic pathways. Hypo-osmotic cell swelling counteracts proteolysis and glycogen breakdown in the liver, whereas hyperosmotic cell shrinkage promotes protein breakdown, glycolysis and glycogenolysis. To investigate the effect of acute changes of extracellular osmolality on whole-body protein, glucose and lipid metabolism in vivo, we studied 10 male subjects during three conditions: (i) hyperosmolality was induced by fluid restriction and intravenous infusion of hypertonic NaCl (2-5%, wt/vol) during 17 h; (ii) hypo-osmolality was produced by intravenous administration of desmopressin, liberal water drinking and infusion of hypotonic saline (0.4%); and (iii) the iso-osmolality study comprised oral water intake ad libitum. Plasma osmolality increased from 285+/-1 to 296+/-1 mosm/kg (P<0.001 during hyperosmolality, and decreased from 286+/-1 to 265+/-1 mosm/kg during hypo-osmolality (P<0.001). Total body leucine flux ([1-(13)C]leucine infusion technique), reflecting whole-body protein breakdown, as well as whole-body leucine oxidation rate (irreversible loss of amino acids) decreased significantly during hypo-osmolality. The glucose metabolic clearance rate during hyperinsulinaemic-euglycemic clamping increased significantly less during hypo-osmolality than iso-osmolality, indicating diminished peripheral insulin sensitivity. Glycerol turnover (2-[(13)C]glycerol infusion technique), reflecting whole-body lipolysis, increased significantly during hypo-osmolar conditions. The results demonstrate that the metabolic adaptation to acute hypo-osmolality resembles that of acute fasting, that is, it results in protein sparing associated with increased lipolysis, ketogenesis and lipid oxidation and impaired insulin sensitivity of glucose metabolism.
European Journal of Clinical Nutrition 12/2003; 57 Suppl 2:S69-74. · 2.46 Impact Factor
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ABSTRACT: The prevalence of obesity is increasing world wide, resulting in morbidity, mortality, and reduced quality of life. The aim of this study was to assess comorbidities and complaints of subjects with morbid obesity in comparison to milder forms of overweight. Therefore, 299 patients visiting our obesity consultation were examined and surveyed prospectively. 41% of the subjects were morbidly obese showing a significantly higher prevalence of arterial hypertension, edema, dyspnea, eczema and depression. Additionally, sleepiness, reduced work capacity, physical inactivity, disadvantages in social life and disturbed eating habits were observed more frequent. Evaluation of subjects with morbid obesity should include a large spectrum of complications, in order to be able to offer a comprehensive support and treatment.
Praxis 10/2001; 90(37):1569-74.
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ABSTRACT: Bioelectrical impedance analysis (BIA) is widely used as an inexpensive and noninvasive method to provide estimates of body compartments such as total body water, lean body mass and fat mass. The present study was performed to test the reliability of this method during acute changes of extracellular osmolality in eight young health men.
Hyperosmolal isohydration was achieved by overnight infusions of hypertonic saline solutions (2 and 5% NaCl) and thirsting, and hypoosmolal hyperhydration by drinking of free water and overnight application of desmopressin. The control study (isoosmolality) consisted of oral water ad libitum.
When plasma osmolality and sodium concentrations increased (from 285 +/- 1 to 296 +/- 1 mmol/kg (P<0.001) and from 141.9 +/- 0.7 to 148.3 +/- 0.6 mmol/l (P<0.0001)) and total body water remained unchanged, body impedance decreased and calculated total body water increased from 42.7 +/- 2.7 to 45.6 +/- 2.3 liters (P<0.03). In contrast, during hypoosmolal hyperhydration total body water increased by 1.56 +/- 0.17 kg and plasma osmolality decreased from 285 +/- 1 to 272 +/- 1 mmol/kg (P<0.001) and plasma sodium concentrations from 142 +/- 0.5 to 134.8 +/- 0.4 mmol/l (P<0.0001). In spite of these changes of body water, impedance measurements and calculated total body water remained unchanged. During conditions of isoosmolal isohydration (as demonstrated by unchanged plasma sodium concentrations and osmolality) the measurements by BIA also remained unchanged.
Measurements of total body water using BIA under conditions of unknown hydration status (hyper-, hypo- or isohydration) and unknown osmolality (hyper-, hypo- or isoosmolality) may not be reliable. Therefore bioelectrical impedance analysis is not a suitable bedside method to assess changes of body compartments under unstable hydration status.
Clinical Nutrition 10/2000; 19(5):361-6. · 3.73 Impact Factor
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ABSTRACT: Weight loss and protein malnutrition are frequent complications in HIV-infected patients. The effect of an oral nutritional supplement combined with nutritional counselling on whole body protein metabolism was assessed.
HIV-infected individuals with a body mass index < 21 kg m-2 or CD4-T cells < 500 micro L-1 in stable clinical condition were randomly allocated to [1] receive either oral nutritional supplements (containing 2510 kJ, complete macro- and micronutrients) and dietary counselling (n = 8), or [2] identical monitoring but no supplements or specific nutritional advice (controls, n = 7). Whole body leucine kinetics and leucine oxidation rate were determined by [1-13C]-leucine infusions and lean and fat mass were measured before and 12 weeks after intervention.
Leucine oxidation (protein catabolism) decreased in the group receiving nutritional intervention from 0.33 +/- 0.02 to 0.26 +/- 0.02 micromol kg-1 min-1 after 12 weeks (P < 0.05; P < 0.05 vs. control group) but remained unchanged in the control group. Whole body leucine flux showed a tendency to decrease in the intervention group from 1.92 +/- 0.19 to 1.73 +/- 0.14 micromol kg-1 min-1 (P = 0.07) and remained unchanged in the control group (2.21 +/- 0.16 and 2.27 +/- 0.14 micromol kg-1 min-1, respectively). Lean body mass determined by bioelectrical impedance analysis increased in the nutritional intervention group from 84 +/- 2 to 86 +/- 2 per cent (P < 0.05) and fat mass decreased from 17 +/- 2 to 14 +/- 2 per cent (P < 0.05) of total body weight whereas neither mass changed in the control group. Nutritional intervention had no significant effect on lymphocyte CD4 counts, on plasma TNFR 55, TNFR 75 and ILR 2 concentrations and on quality of life.
The data demonstrate an anticatabolic effect of nutritional supplements combined with dietary counselling in HIV-infected subjects. They suggest that diminished whole body protein catabolism resulted in a change of body composition (increased lean mass, decreased fat mass).
European Journal of Clinical Investigation 01/2000; 30(1):87-94. · 3.02 Impact Factor
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ABSTRACT: Chronic glucocorticoid therapy results in negative bone and connective tissue balance. To assess the effects of GH and a combination of IGF-I and GH, 24 healthy male volunteers received in a double blind fashion either recombinant human GH (0.3 IU/kg per day s.c.), or a combination of GH (0.3 IU/kg per day s.c.) and IGF-I (80 microgram/kg per day s.c.) or placebo (saline s.c.) during 6 days of methylprednisolone (0.5 mg/kg per day) treatment. Methylprednisolone decreased serum osteocalcin concentrations during placebo treatment from 32.9+/-2.1 to 9.0+/-1.4 microgram/l (P<0.0001), indicating diminished osteoblast activity, and procollagen type I (PICP) and procollagen type III (PIIINP) to 46 and 70% of baseline respectively (P<0.005), indicating diminished bone (PICP) and soft tissue collagen synthesis (PIIINP). Urinary excretion of pyridinoline, deoxypyridinoline and hydroxyproline increased during treatment with methylprednisolone alone, indicating increased bone resorption (P<0.05 or less). The combination of GH and IGF-I resulted in a significant blunting of the methylprednisolone effect on serum PICP and PIIINP concentrations (P<0.005 or less vs placebo); this effect was in part due to IGF-I, since serum PICP concentrations decreased less in the combination group than during GH treatment alone (P<0.05). In the groups receiving GH and GH combined with IGF-I, urinary hydroxyproline excretion increased more when compared with methylprednisolone alone (P<0.05 or less). These findings demonstrate that only the combination of GH and IGF-I, but not GH alone, markedly counteracts diminished bone and body collagen synthesis caused by glucocorticoids, whereas connective tissue resorption is enhanced during treatment with GH alone and in combination with IGF-I.
Journal of Endocrinology 09/1999; 162(2):259-64. · 3.55 Impact Factor
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ABSTRACT: Changes in extracellular osmolality, and thus in the cellular hydration state, appear to directly influence cell metabolism. The metabolic changes associated with cell swelling are inhibition of glycogenolysis, glycolysis, and proteolysis. Recent studies in our laboratory demonstrated diminished whole-body protein breakdown in humans during an acute hypoosmolar state. Because of the close interrelationship between carbohydrate and fat metabolism, we speculated that adipose tissue lipolysis and fatty acid oxidation are regulated by changes in extracellular osmolality. Therefore, we investigated the effect of artificially induced hypoosmolality on whole-body lipolysis and fat oxidation in seven healthy young men. Hypoosmolality was induced by intravenous administration of desmopressin, liberal ingestion of water, and infusion of hypotonic (0.45%) saline solution. Lipolysis was assessed by a stable-isotope method (2-[13C]-glycerol infusion). The glycerol rate of appearance (Ra), reflecting whole-body lipolysis, was higher under hypoosmolar compared with isoosmolar conditions (2.35+/-0.40 v 1.68+/-0.21 micromol/kg/min, P=.03). This was even more pronounced when lipolysis was suppressed during hyperinsulinemia and euglycemic clamping (0.90+/-0.08 v 0.61+/-0.03 micromol/kg/min, P=.002). However, plasma free fatty acid (FFA), glycerol, ketone body, insulin, and glucagon concentrations and carbohydrate and lipid oxidation measured by indirect calorimetry were not significantly altered by hypoosmolality. Plasma norepinephrine concentrations were lower under hypoosmolar conditions (P<.01 v control). In conclusion, hypoosmolality in vivo results in increased whole-body lipolysis, which is not due to changes in major lipolysis regulating hormones.
Metabolism 04/1999; 48(4):472-6. · 2.66 Impact Factor
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ABSTRACT: To investigate the effect of acute changes of extracellular osmolality on whole body protein and glucose metabolism, we studied 10 male subjects during three conditions: hyperosmolality was induced by fluid restriction and intravenous infusion of hypertonic NaCl [2-5%; (wt/vol)] during 17 h; hypoosmolality was produced by intravenous administration of desmopressin, liberal water drinking, and infusion of hypotonic saline (0.4%); and the isoosmolality study consisted of ad libitum oral water intake by the subjects. Leucine flux ([1-13C]leucine infusion technique), a parameter of whole body protein breakdown, decreased during the hypoosmolality study (P < 0. 02 vs. isoosmolality). The leucine oxidation rate decreased during the hypoosmolality study (P < 0.005 vs. isoosmolality). Metabolic clearance rate of glucose during hyperinsulinemic-euglycemic clamping increased less during the hypoosmolality study than during the isoosmolality study (P < 0.04). Plasma insulin decreased, and plasma nonesterified fatty acids, glycerol, and ketone body concentrations and lipid oxidation increased during the hypoosmolality study. It is concluded that acute alterations of plasma osmolality influence whole body protein, glucose, and lipid metabolism; hypoosmolality results in protein sparing associated with increased lipolysis and lipid oxidation and impaired insulin sensitivity.
The American journal of physiology 01/1999; 276(1 Pt 1):E188-95.
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ABSTRACT: Mutations in the apolipoprotein (apo) B, E (LDL) receptor gene and in the apolipoprotein B-100 gene are the cause of familial hypercholesterolemia (FH) and of familial defective apo B-100 (FDB), respectively. Whether these abnormalities lead to altered production or uptake of very low density lipoprotein (VLDL) or intermediate density lipoprotein (IDL) has not been established previously. Therefore VLDL and IDL apo B-100 kinetics were measured in seven subjects with FH, in six subjects with FDB, and in five normocholesterolemic controls using primed-constant infusions of [1-13C]leucine. Absolute production rates (APR) of VLDL apoB were higher in FH than in controls (27.1+/-1.9 vs. 17.9+/-2.1 mg/kg/day P < 0.03). VLDL APR in FDB were between those of FH and controls (24.3+/-4.8 mg/kg/day), and demonstrated a relatively large inter-individual variability. The increase in VLDL APR in FH resulted in higher fasting serum triglyceride concentrations than in controls (P < 0.05), whereas in FDB triglycerides were between those observed in FH and in controls. A significant correlation was observed between VLDL apoB APR and serum triglycerides in FH and in FDB; the correlation coefficient for all subjects was r = 0.84 (P < 0.0001), indicating that the major determinant of serum triglyceride concentrations was VLDL apoB APR. IDL apoB APR was lower in FH and in FDB compared to controls (P < 0.03 P < 0.02, respectively): and its fractional catabolic rate (FCR) was slightly lower in FH and in FDB, resulting in similar plasma IDL apoB concentrations in all three groups of subjects. IDL apoB APR in FH were negatively correlated with LDL cholesterol concentrations (r = -0.89; P < 0.001); LDL cholesterol concentrations correlated positively with the part of VLDL that did not appear in IDL (r = 0.82 P < 0.02), by-passing therefore the delipidation cascade. In conclusion the data demonstrate increased VLDL apoB production rates in FH. VLDL and IDL kinetics differ when LDL concentrations are elevated either due to a LDL receptor defect or due to defective apolipoprotein B-100.
The Journal of Lipid Research 02/1998; 39(2):380-7. · 5.56 Impact Factor
