Risk factors for recurrent admissions with diabetic ketoacidosis: a case-control observational study.

AIM: To perform a detailed analysis of patients with recurrent diabetic ketoacidosis admissions in order to establish risk factors for readmission. METHODS: The medical records of all adults and young people (> 15 years) with Type 1 diabetes admitted to Auckland City Hospital over a 15-year period from 1997 to 2011 with a primary diagnosis of ketoacidosis were analysed. Patients readmitted with ketoacidosis within 5 years of their index admission were identified and compared with patients without ketoacidosis readmission who were matched for age, gender, ethnicity and duration of diabetes. RESULTS: A total of 268 patients accounted for a total of 412 admissions. In all, 58 patients had more than one admission for diabetic ketoacidosis during this period. Of these, 40 patients readmitted with diabetic ketoacidosis were compared with matched control subjects (n = 40) who had only one admission for diabetic ketoacidosis. The mean ± sd age of the cohort was 31 ± 12 years. The readmission group had more severe diabetic ketoacidosis and poorer glycaemic control. Alcohol abuse was commonly noted in both groups, with insulin dose omission being the main contributor to the development of ketoacidosis. Both groups had high rates of clinic non-attendance. There were no other differences noted between the groups. CONCLUSION: When patients with recurrent diabetic ketoacidosis were matched for age, duration of diabetes, gender and ethnicity with patients who had only one admission for diabetic ketoacidosis, few differences were noted. This makes designing intervention strategies to reduce readmission with diabetic ketoacidosis difficult.

Long-term effectiveness of a community-based model of care in Maori and Pacific patients with type 2 diabetes and chronic kidney disease: a 4-year follow up of the DElay Future End Stage Nephropathy due to Diabetes (DEFEND) study.

BACKGROUND/AIM: The Delay Future End Stage Nephropathy due to Diabetes study was a randomised controlled trial of Maori and Pacific patients with advanced diabetic nephropathy, comparing a community-based model of care with usual care. The intervention group achieved lower blood pressure (BP), proteinuria and less end-organ damage. After the intervention ended, all patients reverted to usual care, and were followed to review the sustainability of the intervention. METHODS: A retrospective observation of 65 patients (aged 47-75 years) with type 2 diabetes, hypertension, chronic kidney disease 3/4 and proteinuria (>0.5 g/day) previously randomised to intervention/community care or usual care for 11-21 months. Follow up thereafter was until death, end-stage renal disease (ESRD) (estimated glomerular filtration rate (eGFR) ≤ 10 mL/min/1.73 m(2) )/dialysis or 1 February 2014. Primary end-points were death and ESRD/dialysis. Secondary outcomes were annualised glomerular filtration rate decline, non-fatal vascular events and hospitalisations. RESULTS: Median (interquartile ranges (IQR)) post-trial follow up was 49 (21-81) months and similar in both groups. The median (IQR) eGFR decline was -3.1 (-5.5, -2.3) and -5.5 (-7.1, -3.0) mL/min/year in the intervention and usual care groups respectively (P = 0.11). Similar number of deaths, renal and vascular events were observed in both groups. At the end of follow up, the number of prescribed antihypertensive medications was similar (3.4 ± 1.0 vs 3.3 ± 1.4; P = 0.78). There were fewer median (IQR) hospital days (8 (3, 18) vs 15.5 (6, 49) days, P = 0.03) in the intervention group. CONCLUSIONS: Short-term intensive BP control followed by usual care did not translate into reduction in long-term mortality or ESRD rates, but was associated with reduced hospitalisations.

Comparison of two low-dose calcium infusion schedules for localization of insulinomas by selective pancreatic arterial injection with hepatic venous sampling for insulin.

OBJECTIVE: Localization of small insulinomas may be difficult. Selective pancreatic arterial injection of calcium with hepatic venous insulin measurement (SACST) has been used for this purpose, but can rarely cause hypoglycaemia. Two low-dose concentrations of calcium, 0·25 and 0·1 of the usual concentration used for the test, have been compared for sensitivity of localization and safety. DESIGN: Selective pancreatic arterial injection of calcium with hepatic venous insulin measurement was performed at calcium concentrations of 0·0025 (Protocol A) and 0·00625 (Protocol B) mEq calcium per kg. The standard concentration is 0·025 mEq/kg. PATIENTS: Twenty one successive patients with biochemical evidence of insulinoma were studied. RESULTS: Using surgical localization as the gold standard, Protocol A had a sensitivity of 91% and Protocol B 75% for correct localization. The false-positive localization rate was 16%. No hypoglycaemia was observed. These results compare favourably with published data using the standard calcium concentration. Selective pancreatic arterial injection of calcium with hepatic venous insulin measurement was superior to localization by noninvasive imaging; in seven cases, SACST was correct when conventional imaging was negative (five) or false positive (two). CONCLUSION: Low concentrations of calcium are effective and safe when performing SACST for localization of insulinoma.

Glucose control peri-myocardial infarction.

This review summarises the available clinical trials data investigating the effects of glucose lowering on mortality in patients admitted to hospital with acute myocardial infarction. The results of these studies are inconclusive with no clear evidence that this intervention has additional benefit over and above routine care.

The effect of atorvastatin on markers of bone turnover in patients with type 2 diabetes.

Retrospective and uncontrolled studies suggest that the lipid-lowering statin class of drugs has either no or beneficial effects on bone density and may reduce fracture risk. We have examined the effects of atorvastatin on serum and plasma markers of bone turnover in 25 patients (age 56 +/- 8 years) with type 2 diabetes (duration: 4.7 +/- 5.0 years, 16 female, 2 insulin-treated, 4 diet alone, and 19 on oral hypoglycemic agents) and baseline hypercholesterolemia (cholesterol 6.6 +/- 0.8 mmol/l) in a double-blind, placebo-controlled, crossover study of 12 weeks of placebo/40 mg of atorvastatin with an 8-week wash-out period. Atorvastatin resulted in a fall in total cholesterol of 2.3 +/- 0.9 mmol/l. There were no effects of active or placebo therapy on total alkaline phosphatase, bone-specific alkaline phosphatase, osteocalcin, or beta C-telopeptide of type 1 collagen (beta-CTX). We conclude that atorvastatin (40 mg/day) has no significant effect on bone turnover in man.

The influences of obesity and glycemic control on endothelial activation in patients with type 2 diabetes.

The aims of this study were to elucidate the factors that contribute to endothelial activation and fibrinolytic abnormalities in patients with poorly controlled type 2 diabetes and to determine whether improved glycemic control reduces endothelial activation. Adhesion molecules [E-selectin, intracellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1], von Willebrand factor, total nitric oxide (NO), endothelin-1, tissue plasminogen activator, and plasminogen activator inhibitor-1 were measured in 43 type 2 diabetic subjects with hemoglobin A1c of 9.0% or more at baseline (compared with 21 healthy controls) who after 20 wk had been randomized to either improved (IC) or usual (UC) glycemic control. At baseline, type 2 diabetic patients had significant endothelial activation and abnormal fibrinolysis compared with control subjects. Body mass index in the diabetic patients was the only independent predictor of E-selectin (P = 0.007), ICAM-1 (P = 0.01), and NO (P = 0.008) concentrations, but not vascular cell adhesion molecule-1, plasminogen activator inhibitor-1, or tissue plasminogen activator (all P > 0.05). Type 2 diabetic patients with a body mass index of 28 kg/m2 or less had concentrations of E-selectin, ICAM-1, endothelin-1, and NO similar to those in healthy controls. After 20 wk, hemoglobin A1c was significantly lower in IC vs. UC (IC, 8.02 +/- 0.25%; UC, 10.23 +/- 0.23%; P < 0.0001), but there were no significant changes in markers of endothelial activation or indexes of fibrinolysis. Obesity appears to be the most important predictor of endothelial activation in patients with type 2 diabetes. Short-term improvement in glycemic control does not appear to reduce endothelial activation.

Effects of improved glycaemic control on endothelial function in patients with type 2 diabetes.

BACKGROUND: Patients with type 2 diabetes have abnormal endothelial function but it is not certain whether improvements in glycaemic control will improve endothelial function. AIMS: To examine the effects of short-term improved glycaemic control on endothelial function in patients with inadequately regulated type 2 diabetes mellitus. METHODS: Forty-three patients with type 2 diabetes and glycosylated haemoglobin (HbA1c) > 8.9% were randomized to either improved glycaemic control (IC) n = 21 or usual glycaemic control (UC) n = 22 for 20 weeks. Using high-resolution B-mode ultrasound, brachial artery flow-mediated dilatation (FMD) and glyceryl trinitrate-mediated dilatation (GTN-D) were measured at baseline and 20 weeks later. RESULTS: After 20 weeks, HbA1c was significantly lower in IC versus UC (IC 8.02 +/- 0.25% versus UC 10.23 +/- 0.23%, P < 0.0001) but changes in FMD and GTN-D were not different between the groups (FMD at baseline and week 20 IC 5.1 +/- 0.56% versus 4.9 +/- 0.56% and UC 4.2 +/- 0.51% versus 3.1 +/- 0.51%; P = 0.23: GTN-D IC 12.8 +/- 1.34% versus 10.4 +/- 1.32% and UC 13.7 +/- 1.2% versus 12.7 +/- 1.23%; P = 0.39). In the IC group weight increased by 3.2 +/- 0.8 kg after 20 weeks compared to 0.02 +/- 0.70 kg in UC (P = 0.003). Blood pressure and serum lipid concentrations did not change in either group. CONCLUSIONS: Short-term reduction of HbA1c levels did not appear to affect endothelial function in patients with type 2 diabetes and previously poorly regulated glycaemic control.

Comparison of ultrasound assessment of flow-mediated dilatation in the radial and brachial artery with upper and forearm cuff positions.

In the published literature relating to flow-mediated dilatation (FMD), there are substantial differences between centres in terms of normal FMD amongst healthy subjects. This present study attempts to identify the effect of differing methodologies on FMD. High frequency ultrasound was used to measure blood flow and percentage brachial and radial artery dilatation after reactive hyperaemia induced by forearm or upper arm cuff occlusion in 24 healthy subjects, less than 40 years, without known cardiovascular risk factors. FMD of the brachial artery was significantly higher after upper arm occlusion, compared with forearm occlusion, 6.4 (3.3) and 3.9 (2.6)% (P<0.05), respectively. FMD of the radial artery was significantly higher after forearm occlusion, compared with upper arm occlusion, 10.0 (4.6) and 7.9 (3.5)% (P<0.05), respectively. The percentage blood flow increase in the brachial and radial arteries after forearm and upper arm occlusion were similar. After forearm and upper arm occlusion, the radial artery percentage dilatation was greater than the brachial artery. In conclusion dilatation of the brachial artery, after reactive hyperaemia induced by upper arm occlusion, was significantly more pronounced compared with dilatation of the brachial artery after forearm occlusion, despite a similar percentage blood flow increase. The local ischaemia of the brachial artery with a proximal occlusion may explain why the brachial artery dilated more after upper arm occlusion compared with after forearm occlusion. The study has also shown that FMD of the radial artery could be assessed by B-mode ultrasound technique. FMD was greater using the radial artery compared with the brachial artery, suggesting that the radial artery may be a useful way to assess FMD in future clinical studies.

The effects of intensive glycaemic control on body composition in patients with type 2 diabetes.

AIM: To examine the effects of improved glycaemic control over 20 weeks on the type and distribution of weight change in patients with type 2 diabetes who at baseline have poor glycaemic control. METHODS: Forty-three patients with type 2 diabetes and HbA1c > 8.9% were randomised to either intensive glycaemic control (IC) n = 21 or usual glycaemic control (UC) n = 22 for 20 weeks. Dual energy X-ray absorptiometry was used to assess the type and distribution of weight change during the study. RESULTS: After 20 weeks HbA1c was significantly lower in patients randomised to IC than UC (HbA1c IC 8.02 +/- 0.25% vs. UC 10.23 +/- 0.23%, p < 0.0001). In the IC group weight increased by 3.2 +/- 0.8 kg after 20 weeks (fat-free mass increased by 1.8 +/- 0.3 kg) compared to 0.02 +/- 0.70 kg in UC (p = 0.003). The gain in total body fat mass comprised trunk fat mass (IC 0.94 +/- 0.5 kg vs. UC 0.04 +/- 0.4 kg, p = 0.18) and peripheral fat mass (total body fat - trunk fat) (IC 0.71 +/- 0.32 kg vs. UC -0.21 +/- 0.28 kg, p = 0.04). Blood pressure and serum lipid concentrations did not change over time in either group. CONCLUSIONS: Intensive glycaemic control was associated with weight gain which was distributed in similar proportions between the central and peripheral regions and consisted of similar proportions of fat and fat-free mass. Blood pressure and serum lipid concentrations were not adversely affected.

The effect of acute hyperglycaemia on brachial artery flow mediated dilatation in normal volunteers.

BACKGROUND: Endothelial function is known to be abnormal in patients with diabetes and acute hyperglycaemia may play an aetiological role. AIMS: The aim of this randomised controlled study was to determine if acute systemic hyperglycaemia impairs endothelial function in normal subjects. METHODS: Endothelial function was assessed by the change in brachial artery diameter in response to forearm ischaemia using B-mode ultrasound in ten healthy subjects (eight male) aged 19-35 years. Brachial artery blood flow velocity and diameter were measured before and after five minutes of forearm ischaemia. Measurements were performed in the supine position after an overnight fast, before and after 60 minute infusions of 0.9% saline or 10% dextrose. Measurements were made on two separate occasions at least 24 hours apart, and subjects were randomised to saline first or dextrose first. The largest diameter measured after ischaemia was divided by the resting arterial diameter to calculate percent dilatation of the artery from baseline, and is reported as flow-mediated dilatation (FMD). RESULTS: Dextrose infusion resulted in a significant rise in mean (SD) serum glucose 5.2 (0.1) to 9.2 (0.3) mmol/L and insulin concentration 6.3 (1.4) to 20.6 (3.7) mU/L p<0.002. Brachial artery blood flow velocity and diameter increased significantly from baseline after ischaemia (p<0.002). Mean FMD (SEM) before and after infusion were not, however, significantly different (p=0.4) (pre-saline 7.3 [1.0]%, post saline 5.2 [1.5]% and predextrose 8.1 [2.0]%, post dextrose 5.9 [1.7]%). CONCLUSIONS: These data suggest that acute hyperglycaemia does not impair FMD in normal subjects.

Outcome of managing impotence in clinical practice.

AIMS: Outside of controlled clinical trials, the outcome of treatment for unselected men with impotence is uncertain. This study aims to describe the clinical course of consecutive, unselected men referred to a specialist endocrinology private practice with a primary diagnosis of impotence. METHODS: Consecutive men referred with a primary diagnosis of impotence between June 1995 and December 1997 were studied. After initial evaluation and appropriate investigation, treatment with testosterone in hypogonadal men and instruction in the use of a vacuum device and intracavernosal alprostadil (Caverject) in all men was offered. All men were followed up by telephone and/or questionnaire about erection outcome three to twelve months later. RESULTS: Nineteen diabetic men, aged 53.1+/-8.2 years and forty non-diabetic men, aged 54.8+/-11.6 years were seen. Follow-up information beyond three months was complete in fifty-three (90%). Eighteen eugonadal men chose no further therapy and four of these men had spontaneous return of erections. Eight men were hypogonadal and potency returned in two of six men treated with replacement testosterone. Nine men used the vacuum device, which was effective in three of them. Forty-one men had a trial of Caverject injection, which was effective in twenty-eight. Only twelve of these men used Caverject for longer than six months. CONCLUSIONS: Return of erections with therapy beyond three months in unselected men with impotence is successful in only about one-third. Unexpected hypogonadism is relatively common in impotent men, but testosterone replacement therapy has a low rate of improving erections. New therapies for impotence need careful follow-up studies to assess their effectiveness in clinical practice.

Physiological control of splanchnic blood flow by adrenaline: studies during acute hypoglycaemia in man.

Superior mesenteric artery blood flow (SMABF) increases significantly during and after the hypoglycaemia reaction in healthy humans. To investigate the mechanisms controlling this phenomenon, SMABF and plasma catecholamines were measured in healthy human volunteers. In 10 controls, hypoglycaemia was induced by insulin infusion (2.5 m-units.min-1.kg-1). In six subjects, beta-blockade by propranolol infusion (0.7 microgram.min-1.kg-1) preceded insulin infusion and was continued throughout the study. Following the hypoglycaemia reaction, the glucose nadir was similar in both groups. In controls, increases in SMABF [42.4+/-6.1% (mean+/-S.E.M.); P<0. 001], cardiac output (34.3+/-2.3%; P<0.001) and pulse rate (from 63. 9+/-2.7 to 82.5+/-3.1 beats/min; P<0.001) occurred. Superior mesenteric artery resistance fell by 32.4+/-3.3% (P<0.001). Under beta-blockade, decreases in SMABF (34.8+/-2.9%; P<0.001) and pulse rate (from 59.5+/-0.2 to 51.8+/-2.2 beats/min; P<0.001) occurred. Superior mesenteric artery resistance increased (peak +30.8+/-12.3%; not significant). Subjects showed greater increases in adrenaline (P<0.006) and noradrenaline (P<0.022) concentrations than controls. Mesenteric hyperaemia associated with hypoglycaemia in man appears to be mediated by a beta-adrenergic mechanism that is activated by increased circulating levels of adrenaline.

Atrial fibrillation: prevalence and management in an acute general medical unit.

BACKGROUND: Atrial fibrillation (AF) is a common comorbid condition in patients admitted to hospital. In managing patients with AF, recent research has highlighted the importance of heart rate control, cardioversion, maintenance of sinus rhythm and anticoagulation for the prevention of thromboembolism. AIM: To determine the prevalence of AF in patients admitted acutely to the general medical service at Auckland Hospital and to assess the adequacy of heart rate control, the number cardioverted and the use of warfarin to prevent thromboembolism. METHODS: Prospective review of all acute admissions to the general medical service over a 12 week period. Information was collected from hospital notes on the patients' present and past medical conditions, admission and discharge cardiac medication and the use of investigations, particularly thyroid function tests and echocardiography. The heart rate on discharge, number cardioverted either during the admission or after discharge and the number given warfarin and aspirin were recorded. RESULTS: One hundred and forty-seven patients (aged 38-96, mean age 76 years and 52% male) were admitted in AF 165 times out of the 1637 admissions over the study period (a prevalence of 10.4%, 95% CI 8.6-11.5%). The main causes of admission were heart failure (23%), pneumonia or sepsis (17%), cerebrovascular accident (CVA) or transient ischaemic attack (TIA) (14%) and ischaemic heart disease (11%). Past medical history included hypertension (46%), ischaemic heart disease (39%), congestive heart failure (58%), valvular heart disease (12%), chronic obstructive airways disease (24%), CVA, TIA or thromboembolic event (24%) and diabetes (17%). Thyroid function tests were performed in 50% of patients and echocardiograms in 38%. Heart rate control at discharge could not be assessed, as this was not recorded prior to any patient's discharge. Seventy-eight per cent of patients were discharged on digoxin but only 29% on drugs that control the heart rate with exercise. Five patients out of 11 considered for cardioversion had a successful cardioversion in hospital and two were later cardioverted as outpatients. Twenty-eight per cent were discharged on warfarin, 33% on aspirin and one patient on both. Fifty-two per cent were considered to have contraindications to warfarin therapy. Prescribing rates for warfarin did not vary according to the patients' clinical risk for thromboembolism. CONCLUSION: AF is a common comorbid condition in the acute general medical ward. Standard investigations were under-utilised. Attention needs to be paid to the recording and control of heart rate at rest and on exercise. Cardioversion is considered infrequently. This patient group had a high risk for thromboembolism and after excluding the large group in whom warfarin was contraindicated, warfarin was still under-utilised.

Increased splanchnic blood flow after hypoglycaemia in diabetic and normal man: evidence against glucagon as a mediator.

Superior mesenteric artery blood flow increases significantly after hypoglycaemia in healthy humans. Glucagon has vasoactive properties but its role in hypoglycaemic hyperaemia is unclear. To assess this role, we studied the superior mesenteric artery blood flow response to hypoglycaemia of patients with uncomplicated Type 1 (insulin-dependent) diabetes mellitus of at least 10 years duration; a group known to have defective glucagon response to hypoglycaemia. Hypoglycaemia was induced using an intravenous infusion of soluble human insulin (2.5 m-units.min-1.kg-1) discontinued at a plasma glucose of 2.5 mmol/l. Superior mesenteric artery blood flow was measured using transcutaneous duplex Doppler ultrasound. Plasma samples were assayed for glucose, insulin, glucagon, catecholamines, growth hormone and cortisol. Plasma glucose concentration fell to a nadir of 1.8 (0.3) mmol/l in patients and 1.4 (0.1) mmol/l in controls. Plasma glucagon concentration was unchanged in patients from a baseline level of 111.7 (13.1) ng/l but rose in controls from 105 (8.5) to a peak of 239 (3.1) ng/l (P<0.001). Superior mesenteric artery blood flow increased in both groups: from 385 (29) to 921 (100) ml/min (140% increase; P<0.05) in patients and from 517 (50) to 790 (67) (53% increase; P<0.001) in controls. This study shows that patients with Type 1 diabetes have a normal splanchnic vascular hyperaemic response to hypoglycaemia despite defective glucagon counter-regulation. These results support our previous work suggesting that glucagon is not a major mediator of this response; it seems likely that circulating adrenaline is the major regulatory mechanism.