Efficacy of a basal bolus insulin protocol to treat prednisolone-induced hyperglycaemia in hospitalised patients.

BACKGROUND/AIM: Few studies have specifically investigated treatment of prednisolone-induced hyperglycaemia. AIM: To determine if a basal bolus insulin (BBI) protocol for inpatient hyperglycaemia is effective in patients prescribed acute prednisolone for an inflammatory disease. METHODS: In a cross-sectional study, 66 patients with type 2 diabetes admitted to a general medical ward and treated with BBI for up to 5 days were studied. Twenty-four patients were taking prednisolone ≥10 mg/day to treat an acute inflammatory disease. The remaining 42 patients were a control group. The primary outcome was mean daily blood glucose level. RESULTS: There were no significant differences in glycosylated haemoglobin (8.1 ± 1.0 vs 8.1 ± 1.6%, P = 0.88), age (77 ± 11 vs 75 ± 14 years, P = 0.57), male sex (63 vs 60%, P = 0.81) or body mass index (30.0 ± 5.3 vs 30.2 ± 11.5 kg/m(2) , P = 0.90) between patients taking prednisolone and controls. Mean daily glucose concentration was higher in patients taking prednisolone than in controls (12.2 ± 0.3 vs 10.0 ± 0.1 mmol/L, P < 0.001). Blood glucose level was higher in patients on prednisolone at 1700 h (14.6 ± 0.6 vs 10.3 ± 0.3 mmol/L, P < 0.001) and 2100 h (14.5 ± 0.6 vs 10.5 ± 0.3 mmol/L, P < 0.001), with no significant differences at 0700 h and 1200 h. These findings occurred despite patients taking prednisolone receiving a higher daily insulin dose than controls (0.67-0.70 vs 0.61-0.65 U/kg, P = 0.001) because of higher doses of ultra-rapid-acting insulin at 1200 h and 1700 h. CONCLUSIONS: Hospitalised patients taking prednisolone had substantial afternoon and evening hyperglycaemia despite receiving BBI via a protocol for inpatient hyperglycaemia. Specific insulin regimens for prednisolone-induced hyperglycaemia are needed that recommend more insulin during this time period.

Quantification and genotyping of lipoprotein lipase in patients with diabetic lipaemia.

AIMS: To determine if diabetic lipaemia is caused by loss of function mutations in the lipoprotein lipase gene, LPL. METHODS: We conducted a case-control study over 2 years in two tertiary care hospitals in South Australia. Six patients with a history of diabetic lipaemia and 12 control subjects, with previous diabetic ketoacidosis and peak triglyceride concentrations < 2.4 mmol/l were included. Participants were well at the time of study investigations. RESULTS: Only one patient with lipaemia had a loss of function mutation in LPL and no functional mutations in APOC2 or GPIHBP1 were identified. The mean lipoprotein lipase concentration was lower in patients with diabetic lipaemia than in control subjects (306 vs. 484 µg/l, P = 0.04). The mean fasting C-peptide concentration was higher in patients with diabetic lipaemia than in control subjects (771 vs. 50 pmol/l; P = 0.001). CONCLUSIONS: Lipoprotein lipase deficiency in patients with a history of diabetic lipaemia was predominantly quantitative, rather than secondary to mutations in LPL, APOC2 or GPIHBP1. The majority of patients with severe hypertriglyceridaemia in diabetic ketoacidosis may have ketosis-prone Type 2, rather than Type 1, diabetes.

Relationship between glycaemia and length of hospital stay during an acute exacerbation of chronic obstructive pulmonary disease.

We have assessed whether glucose concentration and patient outcome are related in hospitalised patients when glycaemia is quantified in detail. Continuous glucose monitoring was performed on 47 consecutive subjects with an acute exacerbation of chronic obstructive pulmonary disease. Length of hospital stay increased by 10% for each mmol/L increase in mean glucose (P = 0.01). In a multivariable analysis, mean glucose was independently associated with length of hospital stay (P = 0.02). These data add weight to evidence that hyperglycaemia may adversely affect patient outcomes in hospitalised patients.

Perioperative management of the hypothalamic-pituitary-adrenal axis in patients with pituitary adenomas: an Australasian survey.

BACKGROUND: There is limited consensus regarding optimal glucocorticoid administration for pituitary surgery to prevent a potential adrenal crisis. AIM: To assess the investigation and management of the hypothalamic-pituitary-adrenal (HPA) axis in patients undergoing trans-sphenoidal hypophysectomy in Australasia. METHODS: A questionnaire was sent to one endocrinologist at each of 18 centres performing pituitary surgery in Australasia. Using hypothetical case vignettes, respondents were asked to describe their investigation and management of the HPA axis for a patient with a: non-functioning macroadenoma and intact HPA axis, non-functioning macroadenoma and HPA deficiency and growth hormone secreting microadenoma undergoing trans-sphenoidal hypophysectomy. RESULTS: Responses were received from all 18 centres. Seventeen centres assess the HPA axis preoperatively by measuring early morning cortisol or a short synacthen test. Preoperative evaluation of the HPA status influenced glucocorticoid prescription by 10 centres, including 2/18 who would not prescribe perioperative glucocorticoids for a patient with a macroadenoma and an intact HPA axis. Tumour size influenced glucocorticoid prescribing patterns at 7/18 centres who prescribe a lower dose or no glucocorticoids for a patient with a microadenoma. Choice of investigations for definitive postoperative assessment of the HPA axis varied with eight centres requesting an insulin tolerance test, four centres a 250 µg short synacthen test and six centres requesting other tests. CONCLUSIONS: There is wide variability in the investigation and management of perioperative glucocorticoid requirements for patients undergoing pituitary surgery in Australasia. This may reflect limited evidence to define optimal management and that further well-designed studies are needed.

Newer options in the management of acromegaly.

Paradigms for managing acromegaly have undergone major changes in the past two decades. This has been brought about by combining surgical, pharmacological and radiotherapeutic approaches that provide tight biochemical control to reduce mortality to that of the general population. The biochemical targets for treatment are a growth hormone of <2.5 ng/mL (approximately 7.5 mU/L) and a normal, age-adjusted insulin-like growth factor-1. Until 20 years ago, dopamine agonists were the only class of pharmaceutical agents available to control acromegaly. They have a limited adjunctive role, even with the development of second-generation selective agonists such as cabergoline. Surgery and radiotherapy were the mainstay of acromegaly management before the advent of the effective pharmacological therapies of the modern era: somatostatin analogues and pegvisomant, a growth hormone receptor antagonist. Somatostatin analogues achieve biochemical control in approximately 60% of patients. Pegvisomant, which is available in the USA and Europe and has just been registered in Australia, normalizes insulin-like growth factor-1 in nearly all patients but has no effect on tumour mass. Surgery is an appropriate first-line therapy for microadenomas as the chance of success is high. For large and/or invasive tumours where the prospect of surgical cure is remote, first-line therapy is somatostatin analogue treatment with debulking surgery having an adjunctive role to achieve tight control or to alleviate compression of the optic chiasm. Although acromegaly remains a challenging disease to manage, the expanding range of therapeutic options is likely to result in a better outcome for patients and offers the potential to tailor therapy based on a patient's individual requirements.

A theorist in industry: can one fall between two stools and still land on one's feet?

Here are reminiscences of some of my interactions with Marshall Stoneham and my career in industry, and particularly of his timely support for my work; and with some illustration of the importance of keeping a firm grasp on basic science to help see the wood from the trees in evaluating new technologies. It is interesting to see that fundamental theory established several decades ago needs to be further developed with some quite radical change of viewpoint when it is applied to new technology; and it is ironic that the impetus for such development of fundamental theory can be technological and commercial, rather than purely academic.

Nonlinear-optical absorption in InGaAs/InAlAs multiple quantum wells.

We have measured the room-temperature intensity dependence of the optical transmission of an In(0.53)Ga(0.47)As/In(0.52)Al(0.48)As multiple-quantum-well structure from 1.5 to 1.7 microm. The absorption is calculated from the transmission by taking into account the wavelength dependence of the reflection coefficients. An intensityof 15 kW cm(-2) is required to reduce the absorption by one half for excitation at the edge of the 1H-lC transition absorption band. For intensities exceeding 10(7) W cm(-2), complete saturation of the absorption is observed. A theoretical model is described that fits the intensity dependence of the absorption right upto saturation at two wavelengths and predicts a carrier lifetime of 0.75 nsec, which has been confirmed by independent measurements.