ACL reconstruction with femoral and tibial adjustable versus fixed-loop suspensory fixation: a retrospective cohort study.

BACKGROUND: Cortical suspensory fixation (CSF) devices gain more and more popularity as a reliable alternative to interference screws for graft fixation in anterior cruciate ligament (ACL) reconstruction. Adjustable-loop fixation may be associated with increased anterior laxity and inferior clinical outcome. The purpose of the study was to compare anterior laxity and clinical outcome after minimally invasive all-inside ACL reconstruction using an adjustable-loop (AL) to a standard technique with a fixed-loop (FL) CSF device. METHODS: Patients who underwent primary single-bundle ACL reconstruction with a quadrupled hamstring autograft at a single institution between 2012 and 2016 were reviewed. In the AL group minimally invasive popliteal tendon harvesting was performed with an all-inside approach (femoral and tibial sockets). In the FL group a traditional anteromedial approach was used for tendon harvesting and a femoral socket and full tibial tunnel were drilled. An objective clinical assessment was performed with Telos x-rays and the International Knee Documentation Committee (IKDC) Objective Score. Patient-reported outcomes (PRO) included the IKDC Subjective Score, the Lysholm Knee Score, the Knee Injury and Osteoarthritis Score (KOOS) and the Tegner Activity Scale. RESULTS: A total of 67 patients were enrolled in this retrospective study with a mean follow-up of 4 (± 1.5) years. The groups were homogenous at baseline regarding age, gender, and the time to surgery. At follow-up, no statistically significant differences were found regarding anterior laxity (AL: 2.3 ± 3 mm vs. FL: 2.3 ± 2.6 mm, p = 0.981). PRO scores were comparable between the AL and FL groups (IKDC score, 84.8 vs. 88.8, p = 0.185; Lysholm 87.3 vs. 89.9, p = 0.380; KOOS 90.7 vs. 91.4, p = 0.720; Tegner 5.5 vs. 6.2, p = 0.085). The rate of saphenous nerve lesions was significantly lower in the AL group with popliteal harvesting of the tendon (8.3% vs. 35.5%, p = 0.014). CONCLUSION: The use of an adjustable-loop device on the femoral and tibial side led to similar stability and clinical results compared to a fixed-loop device.

Incidence, diagnostics and treatment algorithm of nerve lesions after traumatic shoulder dislocations: a retrospective multicenter study.

BACKGROUND: The shoulder is the joint most prone to dislocating in the human body and accounts for 45% of all dislocations. In addition to ruptures of the soft tissue and bony injuries, lesions to vascular structures as well as the brachial plexus and its corresponding nerves might occur. With an incidence of up to 65%, nerve lesions are frequently reported after shoulder dislocations. The aim of this study is to obtain information on epidemiology, diagnostics, treatment and duration until remission or late sequelae after shoulder dislocation and concomitant nerve injury in a large patient cohort. METHODS: The patient cohort consisted of 15,739 patients from three centres who had sustained a shoulder dislocation. All patient files were searched for concomitant injury of the brachial plexus or its corresponding nerves. For epidemiological data analysis, demographic data, clinical follow-ups, electromyography and nerve conduction velocity were evaluated. RESULTS: In total, 60 patients (32 males, 28 females) with a mean age of 60 years (range 19-88 years) met the inclusion criteria. In the majority of patients (n = 51), the trauma mechanism was a trivial fall on the outstretched arm. The most frequent dislocation direction was anterior-caudal in 61.6%, followed by strictly caudal in 16.6%. The brachial plexus was injured in 46 patients (76.6%) and isolated nerve damage was documented in 14 patients (23.3%). Electroneurographic examinations were performed in less than half of the patients (38.3%). CONCLUSION: A combination injury of shoulder dislocation and plexus lesion may occur at any age and sometimes has a poor outcome. Electroneurographic examinations should be implemented when managing these patients as a cost-effective and supportive examination. LEVEL OF EVIDENCE: Level IV, retrospective study.

Long-term results after primary augmented repair of proximal tears of the anterior cruciate ligament with the Kennedy-LAD - Does it work?

BACKGROUND: The purpose of this study was to objectively evaluate the clinical functionality of the knee joint 30 years after surgical augmentation of the ACL with the "Kennedy Ligament Augmentation Device ®" (Kennedy LAD®). METHODS: The patient collective consisted of 41 patients with an average age of 59.51 years (±10.18 standard deviation). Included were all patients treated operatively with a Kennedy LAD® augmented reattachment of the ACL at the Department of Trauma Surgery between 1983 and 1985. The state of the knee joint was evaluated with the following measures: Knee injury and Osteoarthritis Outcome Score, Lysholm Score, Short Form (36) Health Survey, International Knee Documentation Committee Score (IKDC, objective + subjective form) and Tegner Activity Scale. RESULTS: Seven patients (17%) sustained a re-rupture of the Kennedy LAD® augmented ACL after a mean time of 16.28 years. Five of them underwent revision surgery. Another four patients (9.76%) showed an ACL insufficiency in clinical examination. The average IKDC Score was 74.14 ±â€¯16.62, the average Lysholm Score was 86.83 ±â€¯14.10, the average Tegner Activity Scale was 4.34 ±â€¯1.11, and the average Knee injury and Osteoarthritis Outcome Score was 86.25 ±â€¯11.64 at final follow-up. The mean Kellgren Lawrence Score of the operated knee was 2 ±â€¯0.71. CONCLUSION: An overall good outcome 30 years after primary ACL augmented repair with the Kennedy LAD® with an implant survival rate of 73% could be reached. These results therefore support the trend of ACL augmentation in selected cases. LEVEL OF EVIDENCE: Retrospective study, Level IV.

The use of the LARS system in the treatment of AC joint instability - Long-term results after a mean of 7.4 years.

BACKGROUND: The acromioclavicular (AC) joint is of great importance for shoulder stability and one of the most frequently injured regions of the shoulder. HYPOTHESIS: AC joint reconstruction with the ligament augmentation & reconstruction system (LARS™) leads to a good-to-excellent outcome at long-term follow-up. PATIENTS AND METHODS: This study was performed as a retrospective single-centre data analysis of a level-I trauma centre. All patients treated operatively for an acute AC dislocation with the LARS™ between 2003 and 2013 were included. RESULTS: The study group consisted of three female (6%) and 44 male patients (94%) with an average age of 37 years and a minimum follow-up of two years. The overall mean clinical outcomes at latest follow-up were: Constant 93, DASH 2.64, ASES 96, SST 97, UCLA 34 and VAS 0.4-representing a good-to-excellent outcome in all patients. Overall, 45 patients (96%) reported to be very satisfied with the achieved result at latest follow-up. In five patients, (11%) complications occurred during the follow-up period, requiring surgical revision in four of the five patients (80%). CONCLUSION: AC joint reconstruction with the LARS™ achieves good-to-excellent clinical and functional outcomes at long-term follow-up with a surgical revision rate of 8.5%. LEVEL OF EVIDENCE: Retrospective follow-up study, case series, level IV.

Dose relationship of stimulated insulin production following intravenous application of glimepiride in healthy man.

This study evaluates stimulated insulin production rate (incremental AUC x MCR (metabolic clearance rate) of C-peptide) and blood glucose (BG) response after i.v. administration of glimepiride (Hoe 490, GLI, CAS 93479-97-1) (0.25, 0.50, 0.75, 1.00, 1.25, 1.50 mg) in healthy man (27 +/- 4 yrs). It was shown that i.v. bolus administration of GLI (0.25, 0.50, 1.25 and 1.50 mg) caused a dose-related rise in insulin production from 18 +/- 17 to 25 +/- 13, 36 +/- 14 and 54 +/- 34 pmol/kg body weight, respectively. This effect did not yet plateau at 1.5 mg GLI and was paralleled by a fall in BG (decremental area below BG baseline) by 40 +/- 36, 69 +/- 20, 161 +/- 47 and 113 +/- 62 mmol.min/l. It is concluded that insulin release is increased by i.v. GLI in a dose related manner, while a parallel decline in BG was induced only up to 1.25 mg GLI. The less marked fall of BG after injection of 1.50 mg GLI may reflect interference by insulin-counterregulatory hormones secondary to induced hypoglycaemia.

Histochemical changes in pancreatic islets obtained from obese Zucker rats (fa/fa) on a diabetogenic diet. No evidence for non-enzymatic protein glycation in endocrine cells.

Genetically obese Zucker rats (fa/fa) on a diabetogenic diet rich in lard and sucrose develop chronic hyperglycemia accompanied by severe hyperinsulinemia. Non-enzymatically glycated protein content was increased in tendon (p < 0.0001) and aorta (p < 0.04), but not nerve, from hyperglycemic rats as compared to normoglycemic lean litter-mates on a conventional chow diet (mmol furosine/mol tyrosine in tissue hydrolysate from 61-week-old rats: tendon, 29.8 +/- 1.8 vs 25.9 +/- 1.3; aorta, 12.0 +/- 1.0 vs 11.0 +/- 1.1). In pancreatic islets, non-enzymatically glycated protein was neither found in lean rats of any age nor in the obese up to an age of 36 weeks. At an age of 61 weeks, non-enzymatically glycated protein accumulated in islets of obese animals, resulting in levels of 17.02-44.65 mmol furosine/mol tyrosine. This rise in islet glycated protein content was not accompanied by a comparable increase in plasma glycemia, but simultaneous histological examination of pancreatic tissue revealed fibrosis of islets. Fibers were probably of collagenic quality without islet amyloid polypeptide immunoreactivity. Because collagen is known to be highly susceptible to non-enzymatic glycation, we suspect that collagenic fibers but not endocrine cells are the main source of glycated protein accumulation in these islets. Hence, our data do not give evidence that non-enzymatic protein glycation plays a role in the islet degeneration occurring in hyperglycemia. Furthermore, immunohistochemical staining for various endocrine peptides did not suggest loss of any hormone-producing cell type or defective pancreatic hormone production in hyperglycemic old, obese Zucker rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood glucose response to stress hormone exposure in healthy man and insulin dependent diabetic patients: prediction by computer modeling.

To establish a qualitative and quantitative model of blood glucose response to stress hormone exposure, healthy subjects (HS) on and off somatostatin (250 micrograms/h) as well as insulin dependent diabetic patients were infused with either epinephrine (E), glucagon (G), cortisol (F), growth hormone (GH) or with a cocktail of these hormones raising plasma stress hormones to values seen in severe diabetic ketoacidosis. The developed input/output model consists of two submodels interconnected in series plus two additional submodels for correction of gains describing both sensitivity of tissue response and utilisation as well as provision of glucose. It was shown and confirmed experimentally that blood glucose response to stress hormones was essentially nonlinear. Furthermore, the mathematical models for healthy subjects and for insulin dependent diabetic patients proved to be of the same structure and differed only in the values of some typical parameters. The model raises the possibility to describe and in part to predict blood glucose response to stress hormone exposure in healthy man and insulin dependent diabetic patients.

Effect of stress hormones on transsplanchnic balance of exogenous amino acid in healthy man.

The effect of stress hormones on transsplanchnic balance of basal and infused amino acids (AA: Val,Met,Ile,Leu,Phe,Lys,His) was investigated in healthy men without and with added epinephrine (EPI) and dexamethasone (DEX). Concentrations of AA and blood glucose were measured in arterial and hepatic venous blood before and after primed-continuous (t = 120 minutes) AA infusion without (group I: controls; n = 6, 24 +/- 3 years), and with intravenous (IV) EPI infusion (group II: 6 micrograms/min, t = -75 to 120 minutes; n = 6, 26 +/- 5 years) or oral DEX pretreatment (group III: 6 mg/d for 2 days; n = 7, 26 +/- 3 years). In the absence of exogenous AA, EPI was demonstrated to increase estimated hepatic plasma flow (EHPF, mL/min: 1,019 +/- 133 [mean +/- SD] v 737 +/- 153; P less than .01), splanchnic output of glucose (SGO), and splanchnic uptake of total AA (nmol/kg.min: 4,657 +/- 2,014 v 2,802 +/- 704; P less than .05), of Gln (+78%) and of Gly (+100%). DEX did not affect EHPF or SGO, but doubled basal splanchnic AA uptake (5,446 +/- 3,635 nmol/kg.min) and increased that of Gln by 110%. Following AA administration, total splanchnic AA uptake was consistently increased (group I, 8,577 +/- 2,380; II, 8,957 +/- 3,714; III, 10,757 +/- 2,689 nmol/kg.min) as was splanchnic Gln uptake, both of which did not differ versus controls following EPI or DEX exposure. However, metabolic clearance rate (MCR, L/min) of infused AA was elevated by 40% (Met) to 85% (Leu) versus controls in subjects receiving EPI, but unchanged in those receiving oral DEX.(ABSTRACT TRUNCATED AT 250 WORDS)

Lifelong sequential changes in glucose tolerance and insulin secretion in genetically obese Zucker rats (fa/fa) fed a diabetogenic diet.

Life-long sequential changes in glucose tolerance and insulin secretion were investigated in genetically obese Zucker rats (fa/fa) fed a diabetogenic diet rich in lard and sucrose. Comparisons were made with lean littermates (Fa/-) receiving normal chow diet. At 3-month intervals, seven to nine lean and obese rats had two permanent venous catheters implanted, allowing stress- and pain-free sampling of blood before, during, and after substrate administration. Intravenous glucose, iv arginine, and oral glucose tolerance were tested. The obese rats progressively developed hyperglycemia and severe hyperinsulinemia; their basal glycemia reached 8.8 +/- 1.1 vs. 5.8 +/- 0.2 mmol/liter in the lean rats at 46 weeks of age; respective insulinemia was 287.7 +/- 61.9 and 18.1 +/- 2.8 mU/liter (mean +/- SD). In the obese rats a distinct loss in glucose tolerance was seen with progression of age in spite of rising stimulated insulin secretion, which suggests progressive development of insulin resistance without exhaustion of B-cell secretory capacity. Absence of insulin deficiency was also suggested by immunohistochemical staining of pancreatic tissue specimens from obese rats, which showed large populations of insulin-containing cells. Like the obese animals, lean rats exhibited a decrease in insulin sensitivity with age. Relating basal individual glycemia and insulinemia, a rise by 1 mmol/liter in glycemia was associated with a 8.8-fold rise in basal insulinemia in lean rats, but only with a 1.8-fold increase in obese rats. Similar correlations for stimulated glycemia and insulinemia suggest impaired glucose sensitivity of pancreatic B-cells in obese vs. lean rats. In conclusion, hyperglycemia and hyperinsulinemia in insulin-resistant obese Zucker rats on a diabetogenic diet are not characterized by quantitatively deficient B-cell secretory capacity, but, rather, by impaired B-cell sensitivity to glucose with qualitatively intact regulation of glycemia and insulinemia at elevated plasma concentrations.

Lack of effect of tenoxicam on dynamic responses to concurrent oral doses of glucose and glibenclamide.

1. In a single-blind, placebo controlled study the influence of tenoxicam on responses of glucose, insulin and C-peptide to oral doses of glucose and glibenclamide was examined in 16 healthy male volunteers. 2. The subjects received once daily doses of 2.5 mg glibenclamide for 12 days. From day 5 through 12 eight subjects received concomitantly 20 mg tenoxicam once daily and the remaining eight subjects received placebo. 3. On days 1, 4, 5 and 12 glibenclamide was taken with 75 g glucose and blood glucose, serum insulin and C-peptide were measured over 5 h. Plasma levels of glibenclamide and tenoxicam (where appropriate) were followed over 10 h. 4. Characteristic parameters of blood glucose and insulin and C-peptide responses did not change significantly with time (day) and there was no difference between both treatment groups. 5. Baseline insulin increased from 11.7 mu l-1 on day 1 to 15.6 mu l-1 on day 4 (P = 0.009), likewise baseline C-peptide increased from 478 pmol l-1 to 530 pmol l-1 (P = 0.05), but there was no further change in the subsequent treatment period. 6. The AUC of the glibenclamide plasma concentration-time curve did not show changes with time or differences between treatment groups. The mean (s.d.) oral clearance of tenoxicam was 2.5 (1.5) ml min-1 and appeared slightly higher than in previous studies. 7. It was concluded that tenoxicam did not affect overall glycoregulation in healthy subjects under glibenclamide steady state conditions.

Quantitative and qualitative differences in basal and glucose- and arginine-stimulated insulin secretion in healthy subjects and different stages of NIDDM.

To determine quantitative and qualitative differences in insulin secretion equimolar amounts of glucose and arginine were infused in 9 healthy subjects, in 8 individuals each with obesity without and with impaired glucose tolerance, and in non-obese and obese non-insulin-dependent diabetic patients (NIDDM). Insulin secretion was calculated after individual determination of metabolic clearance rate of C-peptide (MCRcp) both as the area under the C-peptide concentration curve times MCRcp, and by a mono-compartment mathematical model, both yielding identical results. MCRcp fell consistently with increasing C-peptide infusion rate (e.g.: healthy subjects: C-peptide, 10 nmol/h, 4.2 +/- 0.4; 20 nmol/h, 3.3 +/- 0.3; 30 nmol/h, 3.1 +/- 0.2 ml/kg.min; p less than 0.05 to p less than 0.01). Basal insulin secretion was 2.1-fold greater in the obese with impaired glucose tolerance than in healthy subjects, but was unchanged in non-obese NIDDM. Glucose and arginine triggered insulin release was greater than in healthy subjects at almost identical area under the respective substrate concentration curve (AUC/kg body weight) in obese subjects without (2-fold) and with impaired glucose tolerance (4-fold), and in NIDDMs following i.v. arginine (2-fold). The mean ratio of incremental insulin release to i.v. glucose and arginine was smaller in NIDDM (normal weight, 1.3 +/- 0.4; obese, 1.0 +/- 0.2) than in healthy (2.0 +/- 0.3), or obese subjects with impaired glucose tolerance (2.8 +/- 0.7). Stimulated C-peptide/insulin ratio was reduced in all patients vs that in healthy subjects (p less than 0.05). We conclude that (a) MCR of C-peptide is in part a saturable process; (b) insulin clearance may be impaired in obesity and NIDDM; and (c) insulin secretion differs in obese states and NIDDM both quantitatively and qualitatively, and thereby separates the two disorders as different entities. In addition, quantitation of insulin release in obese states may also help (d) to better define primary algorithms for insulin replacement in normal- and overweight insulin-dependent diabetic patients.

Contribution of plasma proteins to muscular de novo synthesis of glutamine.

Amino acid balance across the muscle bed is known to be negative in the postabsorptive state. The explanation for such permanent amino acid loss by muscle tissue has to be sought in either its proteolytic breakdown, that of plasma polypeptides and proteins, increased rate of amino acid transport out of the cell, or de novo synthesis of amino acids. To evaluate the contribution of plasma proteins to muscle amino acid release in vitro, hindquarters of 48-hour-fasted rats were perfused with 6 mmol/L glucose Krebs-Ringer buffer containing 20% human erythrocytes and albumin or gamma-globulin at concentrations of 5%, 0.5%, and 0%, respectively. To maintain oncotic pressure, plasma proteins were replaced in the latter protocol by 60-kd dextran. Perfusion for 60 minutes without plasma proteins resulted in a fall in amino acid release by 32% and 23%, respectively, compared with amino acid concentrations in the venous hindquarter effluent during infusion of 5% albumin and gamma-globulin, respectively. The impairment of amino acid release was primarily due to decrease in glutamine generation, which dropped from 327.4 +/- 47.3 and 323.0 +/- 35.7 to 211.9 +/- 22.0 mumol/L, respectively (means +/- SE, n = 7). The present data suggest that the apparent negative nitrogen balance observed across the muscle bed in vitro is not caused solely by muscle degradation but also, to a considerable extent, by proteolytic breakdown of "arterial" plasma protein, whose role in in vivo experiments remains to be established.

Effect of hyperosmolality on basal and hormone-stimulated hepatic glucose metabolism in vitro.

To understand better impairment of glucose utilization in diabetics during a hyperosmolal state, in vitro models were established to evaluate the effects of hyperosmolality on basal glucose uptake as well as glucagon dependent glucose release by isolated hepatocytes. In these studies simulating a hyperglycaemic (40 mmol glucose) and hyperosmolal (up to 500 mosm kg-1, NaCl as added solute) state basal hepatic glucose uptake was reversibly suppressed by 19% when osmolality was increased by as little as 10 mosm kg-1. No such effects on glucose uptake by isolated hepatocytes could be attained when the incubation's fluid osmolality was augmented by the addition of urea or mannitol. Estimations of the transport rates of 3-O-methylglucose and uptake of 2-deoxyglucose at 400 vs. 300 mosm kg-1 revealed that impaired intracellular enzymatic activity but not the transport rate of glucose into the cell were responsible for the hyperosmolal defect as uptake was more reduced (P less than 0.025) by increased osmolality for 2-deoxyglucose (16%) than for 3-O-methylglucose (13%). Glucagon dependent glucose release from isolated hepatocytes was diminished by 17.8% when the osmolality was raised to 400 mosm kg-1 by NaCl as added solute. These data obtained in vitro support the clinical contention that a hyperosmolal state, which corresponds to a loss of fluid in excess of solutes, is able to impair basal hepatic glucose uptake as well as glycogenolytic glucagon action on the liver.

Reduction of postprandial blood glucose by the alpha-glucosidase inhibitor Miglitol (BAY m 1099) in type II diabetes.

The dose-dependency of the effects of the alpha-glucosidase inhibitor Miglitol (Bay m 1099) was investigated in 8 Type II diabetic patients. Administration of increasing doses of Miglitol once daily in the morning on four consecutive days concomitantly with a standardized meal containing 50 g starch led to a dose-dependent reduction in the maximal increase in the postprandial blood glucose level and in postprandial incremental AUC of blood glucose. The latter was significant for 50, 100, 75 and 200 mg Miglitol. Bay m 1099 also markedly retarded the appearance of the peak postprandial blood glucose concentration, which indicates delayed carbohydrate absorption. Serum insulin levels, documented as incremental AUCs of the serum insulin excursions, were not reduced dose dependently, because of the impaired insulin secretory capacity of the patients.

Interaction of sympathomimetics and insulin with hepatic glucose production by isolated perfused rat livers: effects of continuous versus pulsatile infusion.

To elucidate the efficacy of continuous vs. intermittent exposure to epinephrine, phenylephrine, and insulin, hepatic glucose production was monitored in isolated perfused rat livers (means +/- SE, n = 6 each). To this end livers of fed rats were perfused with 5 mM glucose Krebs-Ringer buffer in a nonrecirculating system. Using this model it was shown that intermittent exposure (3 min on/off period, dose reduction -50%) to epinephrine (0.4 microM, alpha + beta-agonist) and phenylephrine (5 microM, alpha-agonist) elicited an almost identical rise in hepatic glucose production [epinephrine: 0.72 +/- 0.08 mmol/(86 min X 100 g BW); phenylephrine: 0.68 +/- 0.07 mmol/(86 min X 100 g BW) as their continuous administration (epinephrine: 0.78 +/- 0.06 mmol/(86 min X 100 g BW); phenylephrine: 0.74 +/- 0.09 mmol/(86 min X 100 g BW)]. Inhibition by insulin (100 mU/liter) given either continuously or intermittently (3 min on/off intervals; dose reduction -50%) was equipotent for epinephrine- and phenylephrine-stimulated hepatic glucose production. When the off period was doubled to 6 min, thereby reducing the total insulin dose to 33%, no significant suppression of epinephrine- and phenylephrine-stimulated hepatic glucose production was observed. From this we conclude that 1) the effect on hepatic glucose production of pulsatile (3 min on/off, dose reduction 50%) and continuous administration is equipotent for the respective action of epinephrine, phenylephrine as well as of insulin; and 2) insulin is more effective (P less than 0.02) in inhibiting hepatic glucose production stimulated by an alpha-agonist (phenylephrine; 5.0 microM) than in counteracting alpha + beta-agonist action (epinephrine; 0.4 microM). The characteristics of hepatic glucose release as stimulated by alpha- and/or beta-adrenergic agonists and its inhibition by continuously or intermittently infused insulin were simulated and described by a computer model. Thereby, no qualitative difference could be demonstrated in alpha- vs. beta-adrenergic agonists action on stimulated hepatic glucose production.

Detrimental effect of hyperosmolality on insulin-stimulated glucose metabolism in adipose and muscle tissue in vitro.

To better understand impairment of glucose utilization in diabetics during a hyperosmolal state, in vitro models were established to evaluate the interdependence of hyperosmolality on basal as well as insulin-dependent glucose uptake by rat epididymal fat pads and diaphragms. Using the epididymal fat pad it was shown that NaCl and urea induced hyperosmolality of 400 and 500 mOsm/kg diminished insulin-stimulated glucose uptake by 35 and 90%, as well as 29 and 68%, respectively. Using rat diaphragm as target tissue for insulin action instead a transient rise in basal (non-insulin-dependent) glucose uptake was seen at 400 but not at 500 mOsm/kg. Associated impairment of insulin-dependent glucose uptake was 30 and 79%, respectively. These in vitro data support our previous clinical contention that a hyperosmolal state, which corresponds to a loss of fluid in excess of solutes, is able to impair basal glucose utilization as well as hormone action on glucose metabolism.

Effect of stress hormones on splanchnic substrate and insulin disposal after glucose ingestion in healthy humans.

To compare cortisol and epinephrine action on oral glucose tolerance, healthy humans were infused with either cortisol (0.1 mg X kg-1 X h-1), epinephrine (5.4 micrograms X kg-1 X h-1), or saline before and after a 75-g glucose load, thereby elevating the respective plasma hormone concentrations into the pathophysiologic range. In the basal state, epinephrine increased arterial concentrations of glucose, beta-hydroxybutyrate, and free fatty acids (FFA) as well as splanchnic output of glucose and beta-hydroxybutyrate and splanchnic FFA more than cortisol. Postprandially, C-peptide release and hyperinsulinemia were blunted by epinephrine initially and increased less thereafter than during cortisol infusion. The rise in arterial glucose after glucose ingestion as calculated by the area under the curve was more marked (P less than .01) after epinephrine [( 1.90 +/- 0.08 M) 150 min] and cortisol [( 1.41 +/- 0.05 M) 150 min] than in the control study [( 1.07 +/- 0.04 M) 150 min]. In parallel, the stress hormones induced an almost identical 24 and 31% rise in mean splanchnic glucose output versus control values (normal, 44.8 +/- 2.5; cortisol, 55.3 +/- 3.3; epinephrine, 58.9 +/- 6.9 g/150 min). The associated rise in arterial concentrations and splanchnic output of insulin above control values was considerably greater during cortisol but unchanged during epinephrine exposure. Epinephrine but not cortisol induced a rise versus the control study in splanchnic uptake of lactate and FFA, as well as in pyruvate output, whereas plasma beta-hydroxybutyrate and acetoacetate remained unchanged. The postprandial splanchnic glucose output-to-splanchnic C-peptide output ratio did not differ from normal during epinephrine but was reduced (P less than .01) during cortisol administration.(ABSTRACT TRUNCATED AT 250 WORDS)