Diabetes at the front door. A guideline for dealing with glucose related emergencies at the time of acute hospital admission from the Joint British Diabetes Society (JBDS) for Inpatient Care Group.

People with diabetes account for nearly one-fifth of all inpatients in English and Welsh hospitals; of these, up to 90% are admitted as an emergency. Most are admitted for a reason other than diabetes with only 8% requiring admission for a diabetes-specific cause. Healthcare professionals working in emergency departments experience numerous clinical challenges, notwithstanding the need to know whether each individual with diabetes requires urgent admission. This document has been developed and written by experts in the field, and reviewed by the parent organizations of the Joint British Diabetes Societies for Inpatient Care-Diabetes UK, the Diabetes Inpatient Specialist Nurse Group and the Association of British Clinical Diabetologists. The document aims to support staff working in emergency departments and elsewhere by offering practical advice and tools for effective, appropriate and safe triage. Each section relates to the commonest diabetic specific emergencies and algorithms can be printed off to enable ease of access and use.

Management of adults with diabetes on the haemodialysis unit: summary of guidance from the Joint British Diabetes Societies and the Renal Association.

Diabetic nephropathy remains the principal cause of end-stage renal failure in the UK and its prevalence is set to increase. People with diabetes and end-stage renal failure on maintenance haemodialysis are highly vulnerable, with complex comorbidities, and are at high risk of adverse cardiovascular outcomes, the leading cause of mortality in this population. The management of people with diabetes receiving maintenance haemodialysis is shared between diabetes and renal specialist teams and the primary care team, with input from additional healthcare professionals providing foot care, dietary support and other aspects of multidisciplinary care. In this setting, one specialty may assume that key aspects of care are being provided elsewhere, which can lead to important components of care being overlooked. People with diabetes and end-stage renal failure require improved delivery of care to overcome organizational difficulties and barriers to communication between healthcare teams. No comprehensive guidance on the management of this population has previously been produced. These national guidelines, the first in this area, bring together in one document the disparate needs of people with diabetes on maintenance haemodialysis. The guidelines are based on the best available evidence, or on expert opinion where there is no clear evidence to inform practice. We aim to provide clear advice to clinicians caring for this vulnerable population and to encourage and improve education for clinicians and people with diabetes to promote empowerment and self-management.

A lady with NASH and choreoathetosis.

We describe a case of acquired hepatocerebral degeneration (AHD) presenting with confusion and worsening memory problems since her discharge from the gastroenterology units. Cases of AHD are rare and are frequently confused with hepatic encephalopathy and Wilson's disease. There are no proven pharmacological therapies for AHD. Information regarding the effect of orthotopic liver transplant on AHD is limited and conflicting. Most patients eventually die from the systemic complications of cirrhotic liver failure including infection, hepatic coma and hepatocellular carcinoma.

Effects of acute hyperglycaemia on anorectal motor and sensory function in diabetes mellitus.

AIMS: To determine the effects of acute hyperglycaemia on anorectal motor and sensory function in patients with diabetes mellitus. METHODS: In eight patients with Type 1, and 10 patients with Type 2 diabetes anorectal motility and sensation were evaluated on separate days while the blood glucose concentration was stabilized at either 5 mmol/l or 12 mmol/l using a glucose clamp technique. Eight healthy subjects were studied under euglycaemic conditions. Anorectal motor and sensory function was evaluated using a sleeve/sidehole catheter, incorporating a barostat bag. RESULTS: In diabetic subjects hyperglycaemia was associated with reductions in maximal (P<0.05) and plateau (P<0.05) anal squeeze pressures and the rectal pressure/volume relationship (compliance) during barostat distension (P<0.01). Hyperglycaemia had no effect on the perception of rectal distension. Apart from a reduction in rectal compliance (P<0.01) and a trend (P=0.06) for an increased number of spontaneous anal sphincter relaxations, there were no differences between the patients studied during euglycaemia when compared with healthy subjects. CONCLUSIONS: In patients with diabetes, acute hyperglycaemia inhibits external anal sphincter function and decreases rectal compliance, potentially increasing the risk of faecal incontinence.

Does insulin lispro preserve the physiological defences to hypoglycaemia during intensive insulin therapy with a conventional basal bolus regimen?

AIM: Insulin lispro used in an intensive basal/bolus regimen produces equivalent glycaemic control to human-soluble insulin but reduces rates of hypoglycaemia. We tested the hypothesis that the use of rapid-acting analogues might prevent the development of defective hypoglycaemic counterregulation during intensive insulin therapy. METHODS: Ten patients with type 1 diabetes (four female, mean age 33 +/- 3 years, diabetes duration 12 +/- 2 years) participated in an open, randomized cross-over study, with 2 months run-in and 4-month treatment periods using either lispro or human-soluble insulin before meals and human NPH insulin (NPH) at night. The total of reported hypoglycaemic episodes (lispro vs. soluble, 123 vs. 128) and HbA(1c) (6.1 +/- 0.2 vs. 6.6 +/- 0.2%) were similar during both treatments. At the end of each period, we measured symptomatic, counterregulatory and cognitive responses, and glycaemic thresholds during hypoglycaemia, induced with a hyperinsulinaemic clamp (blood glucose of 5, 4.5, 3.5 and 2.5 mmol/l). RESULTS: We found similar overall responses of adrenaline, cortisol, growth hormone and total symptom score. Glycaemic thresholds for rises in adrenaline (3.1 +/- 0.2 vs. 3.1 +/- 0.2 mmol/l, p = 0.76), cortisol (2.2 +/- 0.1 vs. 2.2 +/- 0.1 mmol/l, p = 0.16), growth hormone (3.3 +/- 0.15 vs. 2.9 +/- 0.2 mmol/l, p = 0.13), symptoms (3.2 +/- 0.2 vs. 3.3 +/- 0.1 mmol/l, p = 0.051) and impaired cognitive function (3.0 +/- 0.2 vs. 3.0 +/-0.2 mmol/l, p = 0.20) were also similar. CONCLUSION: Four months of intensive treatment, with insulin lispro used pre-prandially and isophane at night, produced relatively preserved but equivalent physiological responses to hypoglycaemia as those on soluble insulin. Longer periods of treatment or alternative regimens may be necessary to demonstrate beneficial effects on hypoglycaemic physiological responses.

The effect of erythromycin on gastric emptying is modified by physiological changes in the blood glucose concentration.

OBJECTIVE: The aim of this study was to determine whether variations in the blood glucose concentration within the normal postprandial range affect the gastrokinetic action of erythromycin. METHODS: Six healthy male volunteers, aged 20-33 yr underwent measurements of gastric emptying on 2 separate days; blood glucose concentrations were maintained at approximately 4 mmol/L (72 mg/dl) on 1 day and at 8 mmol/L (144 mg/dl) on the other. The order of the two studies was randomized and they were separated by 4-7 days. On both days, erythromycin (3 mg/kg) was administered intravenously over 15 min immediately before consumption of 300 g minced beef labeled with 20 MBq 99mTc-sulphur colloid chicken liver and 150 ml water labeled with 67Ga-EDTA. RESULTS: Gastric emptying of solid (p < 0.05) and liquid (p < 0.0001) were slower at a blood glucose concentration of 8 mmol/L (144 mg/dl) when compared to 4 mmol/L (72 mg/dl). The slowing of gastric emptying was associated with greater retention of both solid and liquid in the proximal (p < 0.06) and distal (p < 0.01) stomach. CONCLUSIONS: After administration of erythromycin, gastric emptying and intragastric distribution of solids and liquids is influenced by physiological changes in the blood glucose concentration.

Effects of oral fructose and glucose on plasma GLP-1 and appetite in normal subjects.

Oral glucose is a potent stimulant of glucagon-like peptide-1 (GLP-1) secretion. The effect of oral fructose on GLP-1 secretion in humans is unknown. The aims of this study were to determine (i) whether oral fructose stimulates GLP-1 secretion and (ii) the comparative effects of oral glucose and fructose on appetite. On 3 separate days, 8 fasting healthy males received, in single-blind randomized order (i) 75 g glucose, (ii) 75 fructose, or (iii) 75 g glucose followed by 75 g fructose I h later. Venous glucose, insulin and GLP-1 were measured. Appetite was assessed by visual analog questionnaires and intake of a buffet meal. Whereas glucose and fructose both increased plasma glucose, insulin and GLP-1 (P < 0.000)] for all), the response to glucose was much greater (P < 0.005 for all). There was no increase in plasma GLP-1 when fructose was given after glucose. There was no difference in food intake after oral glucose or fructose. We conclude that oral fructose (75 g) stimulates GLP-1 (and insulin) secretion, but the response is less than that to 75 g glucose. These observations suggest that neither GLP-1 nor insulin play a major role in the regulation of satiation.

Gastric emptying in diabetes mellitus: relationship to blood-glucose control.

The application of novel investigative techniques has established that disordered gastric motility is a frequent complication of diabetes mellitus. Thus, gastric emptying of solid or nutrient liquid meals is abnormal in 30% to 50% of randomly selected outpatients with long-standing type 1 or type 2 diabetes. Delayed gastric emptying occurs more frequently than rapid emptying. There is increasing evidence that disordered gastric motility has a major impact on the management of patients with diabetes mellitus by leading to gastrointestinal symptoms and poor glycemic control. Although both gastroparesis and upper gastrointestinal symptoms have been attributed to irreversible autonomic damage, it is now clear that acute changes in the blood-glucose concentration have a major effect on both gastrointestinal motor function and the perception of sensations arising in the gut. For example, there is an inverse relationship between the rate of gastric emptying and the blood-glucose concentration, so that gastric emptying is slower during hyperglycemia and accelerated during hypoglycemia. This article reviews some issues in the etiology, diagnosis, and management of problems associated with gastric emptying in elderly persons with diabetes mellitus.

Hyperglycemia attenuates the gastrokinetic effect of erythromycin and affects the perception of postprandial hunger in normal subjects.

OBJECTIVE: The major aims of this study were to determine in normal subjects whether the effects of erythromycin on gastric emptying, postprandial hunger, and fullness are modified by the blood glucose concentration. RESEARCH DESIGN AND METHODS: A total of 10 normal subjects (aged 20-39 years) underwent concurrent measurements of gastric emptying, blood glucose, hunger, and fullness on four separate occasions: twice during euglycemia (approximately 4 mmol/l) and twice during hyperglycemia (approximately 15 mmol/l). Either erythromycin (3 mg/kg) or saline (0.9%) was administered intravenously immediately before ingestion of a radioisotopically labeled solid meal. RESULTS: Gastric emptying was slower (P < 0.0001) during hyperglycemia when compared with euglycemia after both erythromycin and saline administration. During hyperglycemia, erythromycin reduced the lag phase (77.8 +/- 12.6 vs. 20.3 +/- 7.3 min; P < 0.05) but had no effect on the postlag emptying rate (0.32 +/- 0.077% per min vs. 0.24% per min). Hunger decreased (P < 0.001) and fullness increased (P < 0.001) after the meal. Postprandial hunger was less during hyperglycemia after saline infusion (P < 0.05) but not after erythromycin. Hunger was greater after erythromycin during both hyperglycemia and euglycemia (P < 0.05). CONCLUSIONS: At a blood glucose concentration of approximately 15 mmol/l, 1) gastric emptying of a solid meal is slower, when compared with euglycemia, even after administration of erythromycin; 2) the effect of erythromycin on gastric emptying of a solid meal is attenuated; and 3) the perception of postprandial hunger is reduced.

Natural history of diabetic gastroparesis.

OBJECTIVE: The major aim of this study was to evaluate the prognosis of diabetic gastroparesis. RESEARCH DESIGN AND METHODS: Between 1984 and 1989, 86 outpatients with diabetes (66 type 1, 20 type 2; 40 male, 46 female) underwent assessment of solid and liquid gastric emptying and esophageal transit (by scintigraphy), gastrointestinal symptoms (by questionnaire), autonomic nerve function (by cardiovascular reflex tests), and glycemic control (by HbAlc and blood glucose concentrations during gastric emptying measurement). These patients were followed up in 1998. RESULTS: Of the 86 patients, solid gastric emptying (percentage of retention at 100 min) was delayed in 48 (56%) patients and liquid emptying (50% emptying time) was delayed in 24 (28%) patients. At follow-up in 1998, 62 patients were known to be alive, 21 had died, and 3 were lost to follow-up. In the group who had died, duration of diabetes (P = 0.048), score for autonomic neuropathy (P = 0.046), and esophageal transit (P = 0.032) were greater than in those patients who were alive, but there were no differences in gastric emptying between the two groups. Of the 83 patients who could be followed up, 32 of the 45 patients (71%) with delayed solid emptying and 18 of the 24 patients (75%) with delay in liquid emptying were alive. After adjustment for the effects of other factors that showed a relationship with the risk of dying, there was no significant relationship between either gastric emptying or esophageal transit and death. CONCLUSIONS: In this relatively large cohort of outpatients with diabetes, there was no evidence that gastroparesis was associated with a poor prognosis.

Euglycaemic hyperinsulinaemia does not affect gastric emptying in type I and type II diabetes mellitus.

Hyperglycaemia slows gastric emptying in both normal subjects and patients with diabetes mellitus. The mechanisms mediating this effect, particularly the potential role of insulin, are uncertain. Hyperinsulinaemia has been reported to slow gastric emptying in normal subjects during euglycaemia. The purpose of this study was to evaluate the effect of euglycaemic hyperinsulinaemia on gastric emptying in Type I (insulin-dependent) and Type II (noninsulin-dependent) diabetes mellitus. In six patients with uncomplicated Type I and eight patients with uncomplicated Type II diabetes mellitus, measurements of gastric emptying were done on 2 separate days. No patients had gastrointestinal symptoms or cardiovascular autonomic neuropathy. The insulin infusion rate was 40 mU x m(-2) x min(-1) on one day and 80 mU x m(-2) x min(-1) on the other. Gastric emptying and intragastric meal distribution were measured using a scintigraphic technique for 3 h after ingestion of a mixed solid/liquid meal and results compared with a range established in normal volunteers. In both Type I and Type II patients the serum insulin concentration had no effect on gastric emptying or intragastric meal distribution of solids or liquids. When gastric emptying during insulin infusion rates of 40 mU x m(-2) x min(-1) and 80 mU x m(-2) x min(-1) were compared the solid T50 was 137.8+/-24.6 min vs. 128.7+/-24.3 min and liquid T50 was 36.7+/-19.4 min vs. 40.4+/-15.7 min in the Type I patients; the solid T50 was 94.9+/-19.1 vs. 86.1+/-10.7 min and liquid T50 was 21.8+/-6.9 min vs. 21.8+/-5.9 min in the Type II patients. We conclude that hyperinsulinaemia during euglycaemia has no notable effect on gastric emptying in patients with uncomplicated Type I and Type II diabetes; any effect of insulin on gastric emptying in patients with diabetes is likely to be minimal.

The effect of single doses of pramlintide on gastric emptying of two meals in men with IDDM.

In a previous study we have shown that an intravenous infusion of pramlintide (an analogue of human amylin) delayed gastric emptying, but the dose of pramlintide was supraphysiological in relation to the amylin response to food in non-diabetic subjects. The purpose of this study was to examine the dose response relationship of subcutaneous injections of pramlintide on gastric emptying and to determine whether administration of the drug before one meal has an impact on the subsequent meal. Eleven men with insulin-dependent diabetes mellitus were studied in a double-blind, randomised, four-way crossover design. None had autonomic neuropathy. Euglycaemia was maintained overnight before the study day. At -30 min the patients self-injected their usual morning insulin and at -15 min they injected the study drug (either placebo or 30, 60 or 90 microg pramlintide) subcutaneously. At 0 min they ate a standard meal consisting of a pancake, labelled with 99mTc, and a milkshake containing 3-ortho-methylglucose (3-OMG). Gastric emptying images were obtained for the next 8 h. At 240 min the subjects ate a similar meal, but on this occasion the pancake was labelled with (111)In. All three doses of pramlintide delayed emptying of the solid component of the first meal (p < 0.004) with no significant difference between the drug doses. There were no differences between placebo and pramlintide after the second meal. All three doses of pramlintide resulted in a prolongation in the time to peak plasma 3-OMG level (p < 0.0001) after the first meal but there was no difference after the second meal.

Effect of euglycaemic hyperinsulinaemia on gastric emptying and gastrointestinal hormone responses in normal subjects.

Several studies have shown that hyperglycaemia slows gastric emptying in normal subjects and patients with diabetes mellitus but whether hyperinsulinaemia per se has an effect remains debatable. In the present study we have assessed the effect of hyperinsulinaemia on gastric emptying of a solid and liquid meal in normal subjects. Ten men were studied three times in random order. After an overnight fast, subjects were infused with 0.9% NaCl on two occasions and on the third with insulin, at 40 mU x m(-2) x min(-1) with 20% glucose simultaneously to maintain euglycaemia. Steady-state glucose infusion rate was ensured before the subjects ate a standard meal of a pancake labelled with 99mTc and milkshake labelled with (111)In-DTPA. Gamma-scintigraphic images were then obtained every 20 min for the next 3 h. There were no significant differences between the mean half-emptying times (T50) of the solid and liquid during the two saline infusions (129.6 +/- 28.5 vs 128.4 +/- 23.8 min for the solid and 25.4 +/- 7.0 vs 34.7 +/- 18.0 min for the liquid, mean +/- SD). Hyperinsulinaemia delayed both solid (mean T50 149.6 +/- 30.7, p = 0.031) and liquid emptying (mean T50 39.8 +/- 13.9, p = 0.042). There were no significant differences in the cholecystokinin and glucagon-like peptide 1 responses to the meal during either saline or insulin infusions. There was a tendency towards a greater insulin response to the meal during the hyperinsulinaemic study. Thus, hyperinsulinaemia delayed emptying of both the solid and liquid components of the meal.

Intravenous lactate prevents cerebral dysfunction during hypoglycaemia in insulin-dependent diabetes mellitus.

1. Intravenous lactate prevents cerebral dysfunction during hypoglycaemia in healthy volunteers. This study examines whether this also occurs in insulin-dependent diabetes. Changes in four-choice reaction time, auditory brain stem response, and P300 latency were used as measures of cerebral function. 2. Ten subjects were studied twice at least 4 weeks apart. Blood glucose was maintained between 5 and 8 mmol/l for 1 h before starting a 60 m-unit min-1 m-2 stepped hyperinsulinaemic clamp, achieving blood glucose concentrations of 4.5, 3.3 and 2.5 mmol/l. At one visit, 40 mumol min-1 kg-1 sodium lactate was infused, and at the other, normal saline. Cerebral function was measured at each blood glucose concentration. 3. Blood lactate rose to 3.32 +/- 0.06 mmol/l during lactate infusion compared with 0.9 +/- 0.03 mmol/l during saline infusion. Compared with the results at 4.5 mmol/l there were no significant changes at 3.3 mmol/l in any measure of cerebral function at either visit. At 2.5 mmol/l a significant increase in reaction time and P300 latency occurred with saline [mean change 33.1 +/- 8.6 ms (P < 0.01) and 30.1 +/- 9.2 ms (P < 0.01) respectively] but not lactate [mean change -5.9 +/- 3.7 ms (P > 0.05) and -6 +/- 7.6 ms (P > 0.05) respectively]. No significant changes occurred in auditory brain stem response. The catecholamine response to hypoglycaemia was attenuated by lactate (P < 0.05 for adrenaline and noradrenaline). 4. Thus intravenous lactate prevents cerebral dysfunction during hypoglycaemia in insulin-dependent diabetes.

Well-being, cerebral function, and physical fatigue after nocturnal hypoglycemia in IDDM.

OBJECTIVE: This study assessed the effect of nocturnal hypoglycemia on well-being cerebral function, and physical fatigue the next day in 10 subjects with IDDM. RESEARCH DESIGN AND METHODS: After an exercise test to determine work-loads corresponding to 30 and 60% VO2max, volunteers were studied twice, 4 weeks apart. Blood glucose was lowered one night to 2.3-2.7 mmol/l for 1 h, and at the control visit, hypoglycemia was avoided. The next morning, well-being was assessed using the minor symptom evaluation profile (MSEP), and cerebral function was assessed with the paced auditory serial addition test, the digit symbol substitution test, trail making part B, four-choice reaction time, and auditory P300 latency. Subjects then exercised at predetermined workloads corresponding to 30% VO2max for 30 min and 60% VO2max until exhaustion. Fatigue was assessed every 10 min using the Borg scale for rating of perceived exertion. RESULTS: All three components of the MSEP scored higher (indicating more symptoms) after the hypoglycemic night compared with the control night (P < 0.01 contentment, sleep; P < 0.001 vitality). None of the cerebral function tests performed the next day was affected by hypoglycemia. Exercise capacity was similar at both visits, but subjects were more fatigued after the hypoglycemic night (P < 0.01, analysis of variance). There were no differences in potassium, catecholamine, glucose, or lactate concentrations between visits either before or during exercise. CONCLUSIONS: One hour of hypoglycemia at night affects a subject's sense of well-being, but not cerebral function, the next day. The greater fatigue after the hypoglycemic night cannot be explained by the biochemical parameters measured.

Reproducibility of gastric emptying of a pancake and milkshake meal in normal subjects.

Comparisons of gastric emptying between different centres are difficult because of wide variations in methods. Reproducibility of a method is very important before it is used to compare different subjects or to assess the effect of treatment. The aim of this study was to measure the reproducibility of gastric emptying of a solid and liquid meal in normal subjects. Ten males were studied on two occasions. After an overnight fast, the subjects ate a radiolabelled solid and liquid meal. There were no significant differences in T50 on the 2 days (136.6 +/- 23.2 vs 121.3 +/- 26.7 min for solid and 30.7 +/- 12.6 vs 32.6 +/- 18.7 min for liquid; mean +/- SD). Intra-subject variability was between 7 and 21% for the solid component and 1.5 and 63% for the liquid component. The mean difference in T50 between the 2 days was 15.3 +/- 21.9 min for the solid component and -5.1 +/- 19.7 min for the liquid component. Only one difference between the T50 results was not in the 95% confidence interval for the liquid component. Thus despite some inter- and intra-subject variability, the method showed good reproducibility.