Comparison of hyperinsulinaemic clamp experiments using venous, ‘arterialized’ venous or capillary euglycaemia

SUMMARY. It has been suggested that deviations from arterial euglycaemia during hyperinsulinaemic clamp experiments that use venous plasma glucose measurements may alter the results of such tests (glucose infusion rate, C-peptide suppression, etc.) and that ‘arterialized’ venous blood (‘heated-hand’ technique) may be suitable to circumvent these problems. Therefore, nine normal male fasting volunteers (age 25 ± 4 years, body mass index 23-5± 2–3 kg m^-2) were examined three times using an insulin infusion of 1 mU kg min^-1 over 120 min. Glucose was infused to maintain a concentration of 4–7 mmol 1^-1 (85 mg dl^-1) in venous (V), ‘arterialized’ venous (‘heated-hand’ technique; HH), or capillary (C) plasma. The ‘heated-hand’ technique caused a rise in (rectal) body temperature of 0–3 ± 0-l°C (P < 0–0001). Whereas the glucose aim was reached to a similar degree in all experiments (P = 0–36), capillary glucose concentrations differed slightly, but significantly (higher in experiments with venous and ‘arterialized’ venous blood specimens; P = 0–034). There were no significant differences regarding steady-state insulin concentrations (P = 0–77), glucose infusion rates (V, 7-1 ± 0–5; HH, 7-2 ± 0–6; C, 6-4 ± 0–5 mg kg^-1 min^-1; P = 0–98), C-peptide suppression (P = 0–78), reduction in glucagon (P = 0–27) and free fatty acids (P = 0–16), and all parameters of indirect calorimetry (non-protein RQ: P = 0–67; glucose and lipid oxidation: P = 0–72 and 0–46 respectively; and energy expenditure: P = 0–42). Therefore, hyperinsulinaemic clamp experiments performed using venous, ‘arterialized’ venous, or capillary euglycaemia appear to be almost equally useful for the determination of insulin sensitivity and C-peptide or glucagon suppression. The elevation in body temperature that accompanies use of the ‘heated-hand’ technique does not noticeably influence measured metabolic parameters.     

Effects of liraglutide on postprandial insulin and glucagon responses in Japanese patients with type 2 diabetes

This study assessed the endocrine pancreatic responses to liraglutide (0.9 mg once a day) during normal living conditions in Japanese patients with type 2 diabetes. The study included 14 hospitalized patients with type 2 diabetes. Meal tests were performed after improvement of glycemic control achieved by two weeks of multiple insulin injection therapy and after approximately two weeks of liraglutide treatment. Continuous glucose monitoring was performed to compare daily variation in glycemic control between multiple insulin injection therapy and liraglutide treatment. Liraglutide reduced plasma glucose levels after the test meals (60–180 min; p<0.05), as a result of significant increases in insulin secretion (0–180 min; p<0.05) and decreases in the incremental ratio of plasma glucagon (15–60 min; p<0.05). Continuous glucose monitoring showed that liraglutide treatment was also associated with a decrease in glucose variability. We also demonstrated that optimal glycemic control seen as a reduction in 24-h mean glucose levels and variability was obtained only with liraglutide monotherapy. In conclusion, liraglutide treatment increases insulin secretion and suppresses glucagon secretion in Japanese patients with type 2 diabetes under normal living conditions. The main therapeutic advantages of liraglutide are its use as monotherapy and its ability to decrease glucose variability.     

On the diabetogenic effect of growth hormone in man: effects of growth hormone on glucagon and insulin secretion

Abstract. The effects of human growth hormone (GH) on glucose homeostasis and the secretion of insulin and glucagon was investigated in eighteen healthy subjects. GH (40 μg/kg) was given as a 30 min i.v. infusion and was followed immediately, or after 60 min, by either a glucose infusion, or an i.v. L-arginine infusion or i.v. insulin (005 IU/kg).
An insulin-like effect of GH was seen about 15 min after the start of the GH infusion, and became a diabetogenic action 90 min later. Basal and glucose stimulated insulin secretion were suppressed 60 min after the start of the GH infusion, while insulin response to i.v. L-arginine, on the whole, was uninfluenced. Basal glucagon as well as glucagon response to arginine or hypoglycaemia were uninfluenced by GH. GH did not alter the degree of hypoglycaemia reached after i.v. insulin, whereas the rapidity of blood glucose fall was significantly decreased. The restitution of blood glucose after its nadir was not modified by the hormone.
These results demonstrate that the diabetogenic action of GH is not mediated by GH effects on glucagon secretion, and that GH is of little importance in the acute counter-regulation of insulin-induced hypoglycaemia.     

Insulin deficiency and insulin resistance in Type 2 (non-insulin-dependent) diabetes: quantitative contributions of pancreatic and peripheral responses to glucose homeostasis

A non-steady state dose-response study was designed to quantitate peripheral sensitivity to insulin and pancreatic responsiveness to glucose, and to assess their relative contribution to glucose intolerance in Type 2 diabetes (Type 2 DM, non-insulin-dependent). Eleven lean and eleven obese patients with mild diabetes (fasting plasma glucose, FPG, 10.3 +/- 1.0 and 9.4 +/- 0.6 mmol l-1, respectively) were examined; twenty-six lean and twelve weight-matched obese subjects served as controls. Pancreatic response was measured by sequential injection of 0.1, 0.3 and 0.9 g kg-1 glucose; peripheral sensitivity to insulin was determined from the rate of clearance (Kgluc) of 0.3 g glucose injected sequentially together with 25, 50 and 100 mU insulin kg-1 or with 0, 12.5 and 50 mU kg-1, under somatostatin infusion. The mean dose-response curve describing glucose-induced insulin release showed increased maximal capacity to secrete insulin in obese controls, while the responses of lean as well as obese Type 2 DM were reduced by more than 80%. The mean dose-response curves relating plasma exogenous insulin levels to Kgluc were similar in lean diabetics and lean controls. The curves of both obese controls and obese diabetics were shifted to the right, demonstrating similar insulin resistance. In four lean controls, sensitivity to insulin was tested also during a hyperglycemic clamp set at 10.3 +/- 0.6 mmol l-1. Hyperglycemia reduced the Kgluc at all insulin levels. Individual dose-response curves were transformed to single weighted numerical pancreatic responsiveness scores [PRS], and peripheral sensitivity scores [PSS].(ABSTRACT TRUNCATED AT 250 WORDS)     

Tranexamic acid for trauma: Filling the ‘GAP’ in evidence

Following findings of the Clinical Randomisation of an Antifibrinolytic in Significant Haemorrhage (CRASH‐2) trial, tranexamic acid (TxA) use post trauma is becoming widespread. However, issues of generalisability, applicability and predictability beyond the context of study sites remain unresolved. Internal and external validity of the CRASH‐2 trial are currently lacking and therefore incorporation of TxA into routine trauma resuscitation guidelines appears premature. The Pre‐hospital Antifibrinolytics for Traumatic Coagulopathy and Haemorrhage (PATCH)‐Trauma study is a National Health and Medical Research Council‐funded randomised controlled trial of early administration of TxA in severely injured patients likely to have acute traumatic coagulopathy. The study population chosen has high mortality and morbidity and is potentially most likely to benefit from TxA's known mechanisms of action. This and further trials involving appropriate sample populations are required before evidence based guidelines on TxA use during trauma resuscitation can be developed.     

Mechanism of oestrogen and progesterone effects on lipid and carbohydrate metabolism: alteration in the insulin: glucagon molar ratio and hepatic enzyme activity

As in women receiving oestrogens the administration of 17beta-oestradiol to ovariectomized female rats caused a rise in fasting plasma triglycerides and a fall in plasma glucose. Progesterone, on the other hand, had no significant effects. In the oestradiol treated rats, the portal vein basal insulin levels were slightly reduced. Oestradiol, however, had a marked suppressive effect on the alpha cells of the pancreas resulting in a greater reduction in basal glucagon and impaired glucagon response to alanine infusions. The relative insulin to glucagon (I/G) molar concentration ratio in portal vein blood was increased. Oestradiol also produced a dose dependent increase in the activity of the liver lipogenic enzymes, acetyl CoA carboxylase and fatty acid synthetase. On the other hand, the activity of the gluconeogenic rate limiting enzyme phosphoenol-pyruvate carboxykinase (PEPCK) was inhibited. The cross-over pattern of gluconeogenic intermediates confirmed inhibition of gluconeogenesis at this step, an effect which is similar to that induced by relative insulin 'excess'. Progesterone produced an increase in the portal vein insulin concentrations. Both the basal and the alanine-stimulated glucagon levels were also increased. The I/G molar ratio in portal vein blood of progesterone treated rats remained unaltered and the hepatic lipogenic and gluconeogenic enzyme activities were similar to control animals. These data suggest that insulin activity is increased relative to glucagon in the liver of oestradiol-treated rats due to the rise in portal vein I/G ratio. The changes in liver lipogenic and gluconeogenic enzymes and the alterations in fasting plasma triglycerides and glucose in response to oestrogens could be secondary to this effect.     

‘Busy Behaviour’ in the ‘Land of the Golden M’: Going Out with Learning Disabled Children in Public Places

Background Research suggests that the inclusion of learning disabled people is contingent, unsatisfactory and incomplete. This paper will take a step back and look at the experiences of mothers of learning disabled children in public places. Methods Seventeen women have taken part in the small scale qualitative study which used a combination of single and group interviews to explore their experiences in public places. Findings Four areas have been identified as having an impact upon the experiences of the mothers and children in public places: the effects of the childrens' learning impairments, structural constraints, the attitudes of others and the attitudes of the mothers. Conclusion The paper will conclude by asking if there is a role for alternative primary communities for learning disabled people and make suggestions for the development of a more ‘learning disabled child‐friendly’ environment.     

Investigating Organizational Culture: A Comparison of a ‘High’‐ and a ‘Low’‐Performing Residential Unit for People with Intellectual Disabilities

Background This pilot study investigates organizational culture in small community‐based residential services for people with intellectual disabilities, one of the under‐researched determinants of staff behaviour and performance. Staff performance is of primary importance in the provision of quality services. Materials and methods Two matched residential units were assessed using COMPASS: A Multi‐Perspective Evaluation of Quality in Home Life, and identified as ‘high’ and ‘low’ performing. The organizational culture of the units was assessed using the Organizational Culture Inventory in order to investigate any associations. Results The unit with better quality outcomes demonstrated a more positive organizational culture overall, with statistically significant lower scores on three negatively influential cultural styles, namely, oppositional, competitive and perfectionistic. Conclusions There may well be a meaningful relationship between organizational culture and quality outcomes, although the nature of this relationship is far from clear. The continuation of investigations into organizational culture is encouraged.     

‘Consolidate or bust’ — the development and evaluation of an academic game in a student nurse introductory course

With nurse education in a state of flux the opportunity exists to reappraise the teaching methods currently used and to consider which will be the most appropriate to prepare the practitioner of the future. This paper examines the possible contribution of one particular teaching medium — the academic game — by describing the development and evaluation of a new game called ‘Consolidate or bust’. The game was introduced as part of a wider programme of curriculum development aimed at providing a more balanced introductory course for new student nurses. The results to date indicate that the application of experiential methods in general, and gaming in particular, constitute a valuable addition to more formal approaches and one that may be perceived very prositively by student nurses. The paper concludes with a call for nurse educators to critically examine their present practice and consider the wider application of less formal methods.