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.

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.

Bone mineral density in patients with treated Addison's disease.

Some studies have reported low bone mineral density (BMD) in patients with Addison's disease, whereas others have found BMD to be normal. It is possible that over-replacement of corticosteroids and adrenal androgen deficiency may contribute to a reduction in BMD in these patients. The aims of this study were to examine BMD using dual-energy X-ray absorptiometry in patients with treated Addison's disease at multiple skeletal sites and to investigate the relationships between these measurements and corticosteroid dose. Nineteen men, 3 premenopausal and 7 postmenopausal women with Addison's disease were studied and data from these patients were analyzed separately and as a group. The mean SEM age and duration of Addison's disease of the men were 44 +/- 3.8 years and 15 +/- 2.2 years, in the premenopausal women 40 +/- 2 years and 5 +/- 2.4 years, and in the postmenopausal women 68 +/- 4 years and 20 +/- 5 years, respectively. Eight men were unexpectedly hypogonadal (serum testosterone <13 nmol/l). BMD was expressed as a percent of values in normal controls (n = 418) adjusted for age, sex, ethnic origin, menopausal status and body weight. In the whole group (n = 29), mean BMD of the patients with Addison's disease was not different from normal at any site [mean (+/- SEM) lumbar spine 99.5% +/- 2.9%; femoral neck 99.3% +/- 2.5%; Ward's triangle 96.2% +/- 3.5%; trochanter 99.2% +/- 2.9%; radius 99.8% +/- 2.1%; total body 98.5% +/- 1.4%]. However, there was a wide range of bone densities, with some patients having a low BMD at multiple sites. Bone density was negatively correlated with current and cumulative corticosteroid dose per kilogram body weight and duration of Addison's disease. In conclusion, BMD in patients with Addison's disease is little different from normal, but may be lower in patients with disease of long duration and a high cumulative corticosteroid dose. Unexpected hypogonadism in men with Addison's disease is common.

Diabetic ketoacidosis in adults at Auckland Hospital, 1988-1996.

BACKGROUND: Diabetic ketoacidosis (DKA) is associated with significant morbidity and mortality. Recent evidence suggests that patients with both type 1 and type 2 diabetes can develop DKA. AIM: To review the experience in managing patients admitted to Auckland Hospital with DKA over an eight year period. METHODS: A retrospective chart review was undertaken to identify patients with a discharge code of DKA admitted to Auckland Hospital between May 1988 and October 1996. RESULTS: One hundred and twenty-five patients were identified who met the defined criteria for DKA. The in-patient mortality for the group was 2.4%. Thirteen patients (10.4%) probably had type 2 diabetes. Thirty-eight (30.4%) patients were admitted to the Department of Critical Care Medicine (DCCM)--these patients had a significantly lower systolic blood pressure and arterial pH, together with a significantly higher admission blood glucose and longer duration of insulin infusion than those not admitted to DCCM. Following their index admission 25% of patients were readmitted to hospital with DKA during the study period. Errors in insulin self-administration that contributed to admission to hospital with DKA were identified in 61% of the patients with known diabetes. CONCLUSIONS: Patients with DKA in this study spent about a week in hospital and a significant proportion were admitted to the DCCM. In spite of this the overall mortality was low. Many of these patients were readmitted to hospital with DKA. A small number of patients with DKA may have type 2 diabetes and may not need long term insulin therapy. More effort on patient education regarding insulin use with illness, may prevent admission to hospital with DKA.

Insulin requirements and metabolic control in children with diabetes mellitus attending a summer camp.

The metabolic control of 33 children aged 7-12 (mean 9.8 years), 19M:14F, with diabetes attending a 7-day physically active summer camp was evaluated. Insulin dose was reduced by 20% on arrival at camp, and adjusted daily to maintain preprandial capillary glucose between 4 and 11 mmol l-1 and overnight glucose above 7 mmol l-1. Despite a mean reduction in insulin dose of 33%, hypoglycaemia was common especially in the first few days of camp. This suggests that on day 1 of a physically active camp an empiric reduction of 30% in insulin dose would be more appropriate. However, it is also essential to increase daily carbohydrate intake and New Zealand's national guidelines for the management of diabetes mellitus in summer camps are being rewritten to include this advice. In addition, extra carbohydrate portions must be given simultaneously with insulin dose reduction, especially in physically active camps.

Metastatic breast cancer 42 years after bilateral subcutaneous mastectomies.

Subcutaneous mastectomy has a possible role as prophylaxis in patients at high risk of developing breast cancer. A case history is presented of a woman who developed metastatic breast carcinoma 42 years after bilateral subcutaneous mastectomies for non-malignant disease. This case is presented to draw attention to the persistent risk of developing breast cancer even decades after subcutaneous mastectomy and to point out that the role of such surgery in preventing breast cancer has still not been clarified. The appropriateness of prophylactic mastectomy for an individual is better assessed on the absolute risk of breast cancer developing over a defined period rather than the relative risk.

Assessing glycaemic control in diabetes: relationships between fructosamine and HbA1C.

AIM: Glycated haemoglobin (HbA1C) has become the internationally established method of assessing long term glycaemic control in people with diabetes. In New Zealand the measurement of glycated albumin (fructosamine), which is substantially cheaper than HbA1C has been widely adopted. In this study we have sought to determine if the value of HbA1C can be reliably estimated from knowledge of plasma fructosamine. METHODS: Fifty subjects with diabetes and stable glycaemic control as assessed by 3-5 simultaneous measurements of HbA1C and fructosamine made sequentially over a median of 6 months, were studied. The relationship between the two measures was assessed by determining 95% prediction intervals for HbA1C from the regression equation relating mean HbA1C and fructosamine. A further 8 subjects with significantly changing glycaemic control were also studied. RESULTS: Mean stable plasma fructosamine and HbA1C measurements were closely correlated (r = 0.661, p < 0.0001) with HbA1C increasing on average 1% for every 56 mumol L-1 increase in fructosamine. The prediction intervals for HbA1C were however wide. Thus at a plasma fructosamine of 350 mumol L-1 the 95% prediction intervals for HbA1C ranged from 6.6 to 11.2% (3 to 11 standard deviations above the mean of the normal reference range). This variability could not be accounted for by the presence of albuminuria or by the exclusion of those subjects with the greatest variability in fructosamine. In the subjects showing changes in glycaemic control, a change in HbA1C of 1% was associated with a change in fructosamine of between 29 and 63 mumol L-1. CONCLUSIONS: Fructosamine levels generally correlate well with HbA1C within a population but the value of HbA1C in an individual cannot be inferred with any reliability from the level of fructosamine, nor can the change in HbA1C be inferred from the change in fructosamine. We suggest that if fructosamine is to be used as an index of glycaemic control in diabetes, it is supplemented by a measurement of HbA1C when fructosamine measurements are stable, in order to determine whether the given value of fructosamine is consistent with the glycaemic control targets for that individual.