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Biomedical subjects

Anders Thorell

Publications and source records attributed to Anders Thorell.

16 recordsLinked to original sources
PubMed2006

Postoperative parenteral nutrition while proactively minimizing insulin resistance.

OBJECTIVE: We compared the metabolic effects of postoperative total parenteral nutrition (TPN) and hypocaloric glucose after treatment with oral carbohydrates preoperatively and epidural anesthesia to proactively minimize postoperative insulin resistance. METHODS: Thirteen patients undergoing colorectal resections were given oral carbohydrates preoperatively and epidural anesthesia and randomized to TPN or hypocaloric glucose during and after surgery. Insulin sensitivity (hyperinsulinemic clamp [0.8 mU x kg(-1) x min(-1)], normoglycemic clamps [4.5 mM]), and glucose kinetics (6,6(2)H2-D-glucose), were studied before and on postoperative day 3. Indirect calorimetry was performed and nitrogen excretion in urine was measured. Values are presented as mean +/- standard deviation. Analysis of variance, planned comparison, and Bonferroni's correction were used for statistical analysis. RESULTS: Three days after surgery insulin-stimulated whole-body glucose disposal decreased by 24 +/- 11% versus 28 +/- 23% in patients receiving TPN and hypocaloric glucose, respectively (P < 0.05 for both, not significant between groups). Endogenous glucose production during insulin stimulation was increased only in the glucose group after surgery (P < 0.05 versus before). After surgery, insulin-stimulated glucose oxidation was higher after treatment with TPN, whereas fat oxidation was lower (P < 0.05 for both versus glucose treatment). Fat oxidation increased in the glucose group at basal after surgery (P < 0.05 versus before). Nitrogen balance was less negative after treatment with TPN (P < 0.01). CONCLUSIONS: Treatment with TPN does not seem to improve postoperative peripheral insulin sensitivity in patients with minor insulin resistance after pretreatment with preoperative carbohydrates and perioperative epidural anesthesia. Hypocaloric nutrition results in changes in substrate utilization and nitrogen balance resembling starvation, whereas TPN attenuates these changes.

Aged↗
PubMed2006

Exercise training decreases the concentration of malonyl-CoA and increases the expression and activity of malonyl-CoA decarboxylase in human muscle.

The study was designed to evaluate whether changes in malonyl-CoA and the enzymes that govern its concentration occur in human muscle as a result of physical training. Healthy, middle-aged subjects were studied before and after a 12-wk training program that significantly increased VO2 max by 13% and decreased intra-abdominal fat by 17%. Significant decreases (25-30%) in the concentration of malonyl-CoA were observed after training, 24-36 h after the last bout of exercise. They were accompanied by increases in both the activity (88%) and mRNA (51%) of malonyl-CoA decarboxylase (MCD) in muscle but no changes in the phosphorylation of AMP kinase (AMPK, Thr172) or of acetyl-CoA carboxylase. The abundance of peroxisome proliferator-activated receptor (PPAR)gamma coactivator-1alpha (PGC-1alpha), a regulator of transcription that has been linked to the mediation of MCD expression by PPARalpha, was also increased (3-fold). In studies also conducted 24-36 h after the last bout of exercise, no evidence of increased whole body insulin sensitivity or fatty acid oxidation was observed during an euglycemic hyperinsulinemic clamp. In conclusion, the concentration of malonyl-CoA is diminished in muscle after physical training, most likely because of PGC-1alpha-mediated increases in MCD expression and activity. These changes persist after the increases in AMPK activity and whole body insulin sensitivity and fatty acid oxidation, typically caused by an acute bout of exercise in healthy individuals, have dissipated.

AMP-Activated Protein Kinase Kinases↗
PubMed2006

Twelve months' follow-up after treatment with the EndoCinch endoscopic technique for gastro-oesophageal reflux disease: a randomized, placebo-controlled study.

OBJECTIVE: The Bard EndoCinch plication technique has been reported to improve symptoms and reduce oesophageal acid exposure in patients with gastro-oesophageal reflux disease (GORD). However, no placebo-controlled studies have been published as yet. The purpose of this study was to evaluate the effects of the EndoCinch plication technique in a randomized, placebo-controlled setting. MATERIAL AND METHODS: Forty-six otherwise healthy subjects with objectively verified GORD requiring regular use of proton-pump inhibitors (PPIs) were enrolled in the study. Patients were randomized to the EndoCinch plication technique or a sham procedure. Pre- and post-procedure assessments included gastro-oesophageal endoscopy, oesophageal manometry and 24-h pH recording, quality of life (QoL) assessment and use of PPIs. RESULTS: Reflux-specific symptoms and use of PPIs (total intake as well as number of patients not taking PPIs) improved in both groups at 6 weeks and at 3 and 12 months post-procedure (p<0.05) with an increased improvement in the treatment group at 3 months compared to controls (p<0.05 versus sham). There were no inter- or intra-group differences in endoscopic findings, oesophageal manometry or acid exposure before or at 3 or 12 months post-procedure. Gastro-oesophageal endoscopy showed that 71% and 67% of sutures remained at 3 and 12 months, respectively. CONCLUSIONS: Although some short-term effects were achieved, it was found that there were no differences between the treatment and control groups after 12 months and the lack of reduction of oesophageal acid exposure suggests that, in its present form, the EndoCinch plication technique is not to be recommended for use in clinical practice. It is suggested that the lack of long-term effects is primarily due to detachment of the sutures.

Adult↗
PubMed2006

Combined treatment with exercise training and acarbose improves metabolic control and cardiovascular risk factor profile in subjects with mild type 2 diabetes.

OBJECTIVE: The effect of exercise training and acarbose on glycemic control, insulin sensitivity, and phenotype was investigated in mild type 2 diabetes. RESEARCH DESIGN AND METHODS: Sixty-two men and women with type 2 diabetes were randomized to 12 weeks of structured exercise training with or without acarbose treatment or to acarbose alone. Glycemic control was determined by HbA(1c) (A1C), insulin sensitivity (M value) by euglycemic-hyperinsulinemic clamp, and regional fat distribution by computerized tomography and dual X-ray absorptiometry. Physical fitness was determined as maximal oxygen uptake (Vo(2max)). All investigations were performed before and after the intervention. RESULTS: Forty-eight subjects completed the study. Exercise improved M value by 92% (P = 0.017) and decreased total and truncal fat (P = 0.002, 0.001) and systolic blood pressure (P = 0.01) but had no significant effect on Vo(2max) or A1C level. The combination of exercise and acarbose significantly decreased fasting plasma glucose, A1C, lipids, and diastolic blood pressure and increased Vo(2max), whereas effects on M value and body composition were comparable with that of exercise alone. Acarbose alone had no significant effect on either M value or A1C but decreased systolic (P = 0.001) and diastolic blood pressure (P = 0.001) and fasting proinsulin level (P = 0.009). Multiple regression analysis showed that addition of acarbose to exercise improved glycemic control. CONCLUSIONS: In subjects with mild type 2 diabetes, exercise training improved insulin sensitivity but had no effect on glycemic control. The addition of acarbose to exercise, however, was associated with significant improvement of glycemic control and possibly cardiovascular risk factors.

Acarbose↗
PubMed2005

Effect of "preoperative" oral carbohydrate treatment on insulin action--a randomised cross-over unblinded study in healthy subjects.

BACKGROUND AND AIMS: Preoperative intake of a clear carbohydrate-rich drink reduces insulin resistance after surgery. In this study, we evaluated whether this could be related to increased insulin sensitivity at the onset of surgery. Furthermore, we aimed to establish the optimal dose-regimen. METHODS: Six healthy volunteers underwent hyperinsulinaemic (0.8 mU/kg/min), normoglycaemic (4.5 mmol/l) clamps and indirect calorimetry on four occasions in a crossover-randomised order; after overnight fasting (CC), after a single evening dose (800 ml) of the drink (LC), after a single morning dose (400 ml, CL) and after intake of the drink in the evening and in the morning before the clamp (LL). Data are presented as mean+/-SD. Statistical analysis was performed using the Student's t-test and ANOVA. RESULTS: Insulin sensitivity was higher in CL and LL (9.2+/-1.5 and 9.3+/-1.9 mg/kg/min, respectively) compared to CC and LC (6.1+/-1.6 and 6.6+/-1.9 mg/kg/min, P<0.01 vs. CL and LL). CONCLUSIONS: A carbohydrate-rich drink enhances insulin action 3 h later by approximately 50%. Enhanced insulin action to normal postprandial day-time level at the time of onset of anaesthesia or surgery is likely to, at least partly, explain the effects on postoperative insulin resistance.

Administration, Oral↗
PubMed2005

Metabolic perioperative management: novel concepts.

PURPOSE OF REVIEW: This review summarizes novel information regarding the role of metabolic control in the perioperative period. RECENT FINDINGS: Managing perioperative metabolism has recently been shown to be an important way to improve outcomes in surgical care. In particular, postoperative insulin resistance and hyperglycemia have been linked to many common complications. Recent studies have explored the toxicity of hyperglycemia and suggest a causal relation between insulin resistance and complications in the postoperative state. Controlling glucose concentrations with insulin has been shown to also improve protein balance and fat metabolism. In addition, insulin may affect other hormones including insulinlike growth factor-I during surgical stress. Lastly, recent data suggest that hyperglycemia plays an important role in aggravating the inflammatory response, in that overflow of substrates in the mitochondria causes the formation of excess free oxygen radicals and may also alter gene expression to enhance cytokine production. Although overcoming insulin resistance by insulin infusion is one way of combating hyperglycemia, prevention of its development can also be achieved by using epidural blockade to reduce the release of adrenal stress hormones and to control pain, by preoperative carbohydrates instead of overnight fasting, and by minimal invasive surgical techniques. SUMMARY: Minimizing the effects of insulin resistance has been shown to substantially improve outcome after surgical stress.

Diabetes Mellitus↗
PubMed2004

Exercise regulates Akt and glycogen synthase kinase-3 activities in human skeletal muscle.

Activation of Akt and deactivation of GSK3 are critical signals regulating a number of cellular processes in multiple systems. Whether physical exercise alters Akt and GSK3 activity in human skeletal muscle is controversial. beta-Catenin, a GSK3 substrate and important Wnt signaling protein that alters gene transcription, has not been investigated in human skeletal muscle. In the present study, eight healthy human subjects performed 30min of cycling exercise at 75% of maximum workload (submaximal) followed by 6 bouts of 60s at 125% maximum workload (maximal). Biopsies of vastus lateralis muscle were taken at rest (basal), and within 15s following cessation of the submaximal and maximal exercise bouts. Exercise at both submaximal and maximal intensities significantly increased Akt activity (40% and 110%, respectively). Increases in Akt activity were accompanied by increases in Akt Thr(308) and Ser(473) phosphorylation, decreased GSK3alpha activity ( approximately 30% at both intensities), and increased phosphorylation of GSK3alpha Ser(21). Exercise at both intensities also decreased beta-catenin Ser(33/37)Thr(41) phosphorylation (50-60% at both intensities). These results demonstrate that Akt, GSK3, and beta-catenin signaling are regulated by exercise in human skeletal muscle, and as such identify them as possible molecular mediators of exercise's effect on metabolic and transcriptional processes in skeletal muscle.

Adult↗
PubMed2004

Preoperative oral carbohydrate treatment attenuates endogenous glucose release 3 days after surgery.

BACKGROUND & AIMS: Postoperative metabolism is characterised by insulin resistance and a negative whole-body nitrogen balance. Preoperative carbohydrate treatment reduces insulin resistance in the first day after surgery. We hypothesised that preoperative oral carbohydrate treatment attenuates insulin resistance and improves whole-body nitrogen balance 3 days after surgery. METHODS: Fourteen patients undergoing total hip replacement were double-blindly randomised to preoperative oral carbohydrate treatment (12.5%, 800 + 400 ml, n = 8) or placebo (n = 6). Glucose kinetics (6,6-D2-glucose), substrate utilisation (indirect calorimetry) and insulin sensitivity (hyperinsulinaemic-euglycaemic clamp) were measured preoperatively and on the third day after surgery. Nitrogen losses were monitored for 3 days after surgery. Values are mean (SEM). Analysis of variance (ANOVA) statistics were used. RESULTS: Endogenous glucose release during insulin infusion increased after surgery in the placebo group. Preoperative carbohydrate treatment, as compared to placebo, significantly attenuated postoperative endogenous glucose release (0.69 (0.07) vs. 1.21 (0.13)mg kg(-1) x min(-1), P < 0.01), while whole-body glucose disposal and nitrogen balance were similar between groups. CONCLUSIONS: While insulin resistance in the first day after surgery has previously been characterised by reduced glucose disposal, enhanced endogenous glucose release was the main component of postoperative insulin resistance on the third postoperative day. Preoperative carbohydrate treatment attenuated endogenous glucose release on the third postoperative day.

Administration, Oral↗
PubMed2004

Insulin stimulated glucose disposal in peripheral tissues studied with microdialysis and stable isotope tracers.

BACKGROUND & AIMS: Methods to study glucose kinetics in vivo in specific tissues or tissue beds in humans are often not feasible due to invasiveness or costs of equipment needed. Here we investigate whether the loss (fractional extraction) of 2H7-glucose infused via a microdialysis catheter can be used to study glucose disposal in skeletal muscle and subcutaneous adipose tissue. METHODS AND RESULTS: A perfusion period of 2 h was needed to ensure an isotopic steady state in the microdialysis catheters in skeletal muscle and adipose tissue. In six healthy volunteers the fractional extraction increased during a hyperinsulinemic euglycemic clamp in both skeletal muscle and adipose tissue. Following 48 h of starvation in the same subjects, insulin was not able to increase the fractional extraction of 2H7-glucose from the microdialysis in comparison with a baseline measurement. CONCLUSIONS: In response to insulin infusion, the fractional extraction of 2H7-glucose from a microdialysis catheter increases in skeletal muscle and subcutaneous adipose tissue and this increase is blunted during insulin resistance induced by starvation. These results validate that the fractional extraction of a glucose tracers infused via microdialysis can be used as an index of glucose disposal in peripheral tissues or tissue beds.

Adipose Tissue↗
PubMed2004

Microdialysis methods for measuring human metabolism.

PURPOSE OF REVIEW: To discuss the advantages and limitations of the microdialysis technique as a diagnostic and research tool using recent findings on human metabolism. RECENT FINDINGS: Results from several studies have supported the potential of microdialysis as a diagnostic tool for metabolic monitoring in difficult accessible tissues (brain, liver, intestine). However, despite promising results, no clear diagnostic measures have yet emerged. Several studies combining microdialysis with stable isotope tracers have shown that this approach has great potential for studying human metabolism non-invasively in specific tissue beds in a more dynamic way. SUMMARY: Bearing in mind the limitations and assumptions, the microdialysis technique is a useful tool in investigations of human metabolism. Its main advantages are that it can be used safely with low-grade invasiveness in humans, and thereby allows continuous sampling over prolonged periods of time from specific tissues without taking any biopsies. At present, microdialysis would seem to be useful as a diagnostic tool when integrated in the total clinical, physiological and pharmacological evaluation. Within human metabolic research, microdialysis has been and will be a very useful technique.

Brain↗
PubMed2004

Intensive insulin treatment in critically ill trauma patients normalizes glucose by reducing endogenous glucose production.

Critical illness is associated with insulin resistance and hyperglycemia. Intensive insulin treatment to normalize blood glucose during feeding has been shown to improve morbidity and mortality in patients in intensive care. The mechanisms behind the glucose-controlling effects of insulin in stress are not well understood. Six previously healthy, severely traumatized patients (injury severity score > 15) were studied early (24-48 h) after trauma. Endogenous glucose production (EGP) and whole-body glucose disposal (WGD) were measured (6,6-(2)H(2)-glucose) at basal, during total parenteral nutrition (TPN), and during TPN plus insulin to normalize blood glucose (TPN+I). Six matched volunteers served as controls. At basal and TPN, concentrations of glucose and insulin were higher in patients (P < 0.05). During TPN+I, insulin concentrations were 30-fold higher in patients. At basal, WGD and EGP were 30% higher in patients (P < 0.05). During TPN, EGP decreased in both groups but less in patients, resulting in 110% higher EGP than controls (P < 0.05). Normoglycemia coincided with reduced EGP, resulting in similar rates in both groups. WGD did not change during TPN or TPN+I and was not different between the groups. In conclusion, in healthy subjects, euglycemia is maintained during TPN at physiological insulin concentrations by a reduction of EGP, whereas WGD is maintained at basal levels. In traumatized patients, hyperglycemia is due to increased EGP. In contrast to controls, normalization of glucose concentration during TPN needs high insulin infusion rates and is accounted for by a reduction in EGP, whereas WGD is not increased.

Adult↗
PubMed2003

New developments facilitating nutritional intake after gastrointestinal surgery.

PURPOSE OF REVIEW: Conventional perioperative care includes a period of semistarvation before bowel function returns and adequate oral intake is allowed. It has been clearly shown that there is no need for restriction in oral intake after, at least lower, gastrointestinal surgery, and that early oral feeding does not increase the risk for dehiscense of the anastomosis. In contrast, early feeding reduces postoperative complications. Even if early oral intake is allowed, however, it is common that side effects such as nausea and vomiting prevent patients from reaching the target energy intakes. Thus, developing routines and treatments that promote sufficient early oral intake after surgery and maintain adequate energy intake in the postoperative period are probably of great importance for the outcome from surgery. RECENT FINDINGS: There are a number of factors which may facilitate early oral intake after gastrointestinal surgery including effective pain relief using epidural anaesthesia while avoiding opioids, minimizing sodium and fluid administration perioperatively and substantially reducing preoperative fasting. In addition, sufficient preoperative information, intensive mobilization, energy-dense hospital food and oral supplements may all contribute to improved energy intake after surgery. SUMMARY: In general, there is a great need for randomized controlled trials examining factors important for the regulation of oral intake after surgery and also the effects of early oral intake after upper gastrointestinal surgery. Future areas of research may also include regulation of appetite and use of peripherally acting opioid antagonists.

Abdomen↗
PubMed2002

Glucose flux is normalized by compensatory hyperinsulinaemia in growth hormone-induced insulin resistance in healthy subjects, while skeletal muscle protein synthesis remains unchanged.

The aim of this present investigation was to study the relationship between the reduction in insulin sensitivity accompanying 5 days of treatment with growth hormone (GH; 0.05 mg.24 h(-1).kg(-1)) and intracellular substrate oxidation rates in six healthy subjects, while maintaining glucose flux by a constant glucose infusion and adjusting insulin infusion rates to achieve normoglycaemia (feedback clamp). Protein synthesis rates in skeletal muscle (flooding dose of L-[(2)H(5)]phenylalanine) were determined under these conditions. We also compared changes in insulin sensitivity after GH treatment with simultaneous changes in energy requirements, protein synthesis rates, nitrogen balance, 3-methylhistidine excretion in urine, body composition and the hormonal milieu. After GH treatment, 70% more insulin was required to maintain normoglycaemia (P<0.01). The ratio between glucose infusion rate and serum insulin levels decreased by 34% at the two levels of glucose infusion tested (P<0.05). Basal levels of C-peptide, insulin-like growth factor (IGF)-I and IGF-binding protein-3 increased almost 2-fold, while levels of glucose, insulin, glucagon, GH and IGF-binding protein-1 remained unchanged. Non-esterified fatty acid levels decreased (P<0.05). In addition, 24 h urinary nitrogen excretion decreased by 26% (P<0.01) after GH treatment, while skeletal muscle protein synthesis and 3-methylhistidine excretion in urine remained unchanged. Energy expenditure increased by 5% (P<0.05) after treatment, whereas fat and carbohydrate oxidation were unaltered. In conclusion, when glucose flux was normalized by compensatory hyperinsulinaemia under conditions of GH-induced insulin resistance, intracellular rates of oxidation of glucose and fat remained unchanged. The nitrogen retention accompanying GH treatment seems to be due largely to improved nitrogen balance in non-muscle tissue.

Adult↗
PubMed2002

Modulation of post-operative insulin resistance by pre-operative carbohydrate loading.

Insulin resistance develops as a response to virtually all types of surgical stress. There is an increasing body of evidence that suggests that insulin resistance in surgical stress is not beneficial for outcome. A recent large study in intensive-care patients showed that aggressive treatment of insulin resistance using intravenous insulin reduced mortality and morbidity substantially. Similarly, in burn patients, intensive insulin and glucose treatment has been shown to improve N economy and enhance skin-graft healing. In surgical patients insulin resistance has been characterized in some detail, and has been shown to have many similarities with metabolic changes seen in patients with type 2 diabetes. This finding may be important since insulin resistance has been shown to be one independent factor that influences length of stay. When patients about to undergo elective surgery have been treated with glucose intravenously or a carbohydrate-rich drink instead of overnight fasting, insulin resistance was reduced by about half. A small meta-analysis showed that when post-operative insulin resistance was reduced by pre-operative carbohydrates, length of hospital stay was shortened. Overnight intravenous glucose at high doses improved post-operative N economy. This type of treatment has also been shown repeatedly to reduce cardiac complications after open-heart surgery. Furthermore, if the carbohydrates are given as a drink pre-operatively, pre-operative thirst, hunger and anxiety are markedly reduced. In summary, preventing or treating insulin resistance in surgical stress influences outcome. Fasting overnight is not an optimal way to prepare patients for elective surgery. Instead, pre-operative carbohydrates have clinical benefits.

Anxiety↗
PubMed2002

Metformin increases AMP-activated protein kinase activity in skeletal muscle of subjects with type 2 diabetes.

Metformin is an effective hypoglycemic drug that lowers blood glucose concentrations by decreasing hepatic glucose production and increasing glucose disposal in skeletal muscle; however, the molecular site of metformin action is not well understood. AMP-activated protein kinase (AMPK) activity increases in response to depletion of cellular energy stores, and this enzyme has been implicated in the stimulation of glucose uptake into skeletal muscle and the inhibition of liver gluconeogenesis. We recently reported that AMPK is activated by metformin in cultured rat hepatocytes, mediating the inhibitory effects of the drug on hepatic glucose production. In the present study, we evaluated whether therapeutic doses of metformin increase AMPK activity in vivo in subjects with type 2 diabetes. Metformin treatment for 10 weeks significantly increased AMPK alpha2 activity in the skeletal muscle, and this was associated with increased phosphorylation of AMPK on Thr172 and decreased acetyl-CoA carboxylase-2 activity. The increase in AMPK alpha2 activity was likely due to a change in muscle energy status because ATP and phosphocreatine concentrations were lower after metformin treatment. Metformin-induced increases in AMPK activity were associated with higher rates of glucose disposal and muscle glycogen concentrations. These findings suggest that the metabolic effects of metformin in subjects with type 2 diabetes may be mediated by the activation of AMPK alpha2.

AMP-Activated Protein Kinases↗