Association of type 2 diabetes with prolonged hospital stay and increased rate of readmission in patients with lower limb cellulitis.

BACKGROUND/AIMS: Lower limb (LL) cellulitis-related hospitalisations are prevalent in type 2 diabetes subjects. We assess its costs and factors associated with length of stay and readmissions. METHODS: A retrospective case-control study at an urban hospital servicing a multi-ethnic population in New Zealand, where 7% of the adult population is estimated to have diabetes. Admissions with LL cellulitis in 2008-2013 were identified using coding records. Subsequent hospitalisations after 1 month with the same diagnosis were classified as readmissions. Glycaemic control was assessed by HbA1c measured within 6 months of the index admission. RESULTS: There were 4600 admissions with LL cellulitis in 3636 patients, including 719 patients (20%) with type 2 diabetes. Hospital stay was longer for type 2 diabetes patients (median 5.3 vs 3.0 days, P < 0.001), independent of age, ethnicity and HbA1c. Accompanying LL ulceration was more frequent in type 2 diabetes patients (50% vs 17%, P < 0.001); however, admissions remained longer for type 2 diabetes patients without ulceration (median 3.4 vs 2.8 days, P < 0.001). Readmission rates were also higher in type 2 diabetes patients compared to non-diabetes patients (HR 1.7, P < 0.001), even in the absence of ulceration (HR 2.2, P < 0.001). Age, HbA1c and ethnicity did not distinguish those prone to readmissions in the type 2 diabetes cohort. Type 2 diabetes patients accounted for a fifth of all admissions and one third of the estimated costs. CONCLUSIONS: A high proportion of patients with type 2 diabetes was admitted with LL cellulitis. They had significantly longer admissions and higher readmission rates. Age, HbA1c and ethnicity did not predict length of stay or recurrence.

Ethnicity and risk of lower limb amputation in people with Type 2 diabetes: a prospective cohort study.

AIM: Lower limb amputation is a serious complication of diabetic foot disease and there are unexplained ethnic variations in incidence. This study investigates the risk of amputation among different ethnic groups after adjusting for demographic, socio-economic status and clinical variables. METHODS: We used primary care data from a large national multi-ethnic cohort of patients with Type 2 diabetes in New Zealand and linked hospital records. The primary outcome was time from initial data collection to first lower limb amputation. Demographic variables included age of onset and duration since diabetes diagnosis, gender, ethnicity and socio-economic status. Clinical variables included smoking status, height and weight, blood pressure, HbA1c , total cholesterol/HDL ratio and albuminuria. Cox proportional hazards models were used. RESULTS: There were 892 lower limb amputations recorded among 62 002 patients (2.11 amputations per 1000 person-years), followed for a median of 7.14 years (422 357 person-years). After adjusting for demographic and socio-economic variables and compared with Europeans, Maori had the highest risk [hazard ratio (HR) 1.84 (95%CI:1.54-2.19)], whereas East Asians [HR 0.18, (0.08-0.44)] and South Asians [HR 0.39 (0.22-0.67)] had the lowest risk. Adjusting for available clinical variables reduced the differences but they remained substantial [HR 1.61 (1.35-1.93), 0.23 (0.10-0.56) and 0.48 (0.27-0.83), respectively]. CONCLUSIONS: Ethnic groups had significantly different risk of lower limb amputation, even after adjusting for demographic and some major clinical risk factors. Barriers to care should be addressed and intensive prevention strategies known to reduce the incidence of lower limb amputations could be prioritized to those at greatest risk.

New onset diabetes after transplantation: Not another acronym!

New onset diabetes after transplantation is the onset of diabetes in previously non-diabetic individuals extending beyond the first month post-transplantation.

The Diabetes Excess Weight Loss (DEWL) Trial: a randomised controlled trial of high-protein versus high-carbohydrate diets over 2 years in type 2 diabetes.

AIMS/HYPOTHESIS: To compare the effectiveness of low-fat high-protein and low-fat high-carbohydrate dietary advice on weight loss, using group-based interventions, among overweight people with type 2 diabetes. Study design Multicentre parallel (1:1) design, blinded randomised controlled trial. METHODS: Individuals with type 2 diabetes aged 30­75 years and a BMI >27 kg/m2 were randomised, by an independent statistician using sequentially numbered sealed envelopes, to be prescribed either a low-fat high-protein (30% of energy as protein, 40% as carbohydrate, 30% as fat) or a low-fat high carbohydrate(15% of energy as protein, 55%as carbohydrate,30% as fat) diet. Participants attended 18 group sessions over 12 months. Primary outcomes were change in weight and waist circumference assessed at baseline, 6 and 12 months.Secondary outcomes were body fatness, glycaemic control,lipid profile, blood pressure and renal function. A further assessment was undertaken 12 months after the intervention.Research assessors remained blinded to group allocation throughout. Intention-to-treat analysis was performed. RESULTS: A total of 419 participants were enrolled (mean±SDage 58±9.5 years,BMI 36.6±6.5 kg/m2 and HbA1c 8.1±1.2%(65 mmol/mol)). The study was completed by 70%(294/419).No differences between groups were found in change in weight or waist circumference during the intervention phase or the 12-month follow-up. Both groups had lost weight (2­3 kg, p<0.001) and reduced their waist circumference (2­3 cm, p<0.001) by 12 months and largely maintained this weight loss for the following 12 months. By 6 months, the difference in self-reported dietary protein between groups was small (1.1%total energy; p<0.001). No significant differences between groups were found in secondary outcomes: body fatness, HbA1c, lipids, blood pressure and renal function.There were no important adverse effects. CONCLUSIONS/INTERPRETATION: In a 'real-world' setting, prescription of an energy-reduced low-fat diet, with either increased protein or carbohydrate, results in similar modest losses in weight and waist circumference over 2 years

Effects of fenofibrate on renal function in patients with type 2 diabetes mellitus: the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) Study.

AIMS/HYPOTHESIS: Fenofibrate caused an acute, sustained plasma creatinine increase in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) and Action to Control Cardiovascular Risk in Diabetes (ACCORD) studies. We assessed fenofibrate's renal effects overall and in a FIELD washout sub-study. METHODS: Type 2 diabetic patients (n = 9,795) aged 50 to 75 years were randomly assigned to fenofibrate (n = 4,895) or placebo (n = 4,900) for 5 years, after 6 weeks fenofibrate run-in. Albuminuria (urinary albumin/creatinine ratio measured at baseline, year 2 and close-out) and estimated GFR, measured four to six monthly according to the Modification of Diet in Renal Disease Study, were pre-specified endpoints. Plasma creatinine was re-measured 8 weeks after treatment cessation at close-out (washout sub-study, n = 661). Analysis was by intention-to-treat. RESULTS: During fenofibrate run-in, plasma creatinine increased by 10.0 µmol/l (p < 0.001), but quickly reversed on placebo assignment. It remained higher on fenofibrate than on placebo, but the chronic rise was slower (1.62 vs 1.89 µmol/l annually, p = 0.01), with less estimated GFR loss (1.19 vs 2.03 ml min(-1) 1.73 m(-2) annually, p < 0.001). After washout, estimated GFR had fallen less from baseline on fenofibrate (1.9 ml min(-1) 1.73 m(-2), p = 0.065) than on placebo (6.9 ml min(-1) 1.73 m(-2), p < 0.001), sparing 5.0 ml min(-1) 1.73 m(-2) (95% CI 2.3-7.7, p < 0.001). Greater preservation of estimated GFR with fenofibrate was observed with baseline hypertriacylglycerolaemia (n = 169 vs 491 without) alone, or combined with low HDL-cholesterol (n = 140 vs 520 without) and reductions of ≥ 0.48 mmol/l in triacylglycerol over the active run-in period (pre-randomisation) (n = 356 vs 303 without). Fenofibrate reduced urine albumin concentrations and hence albumin/creatinine ratio by 24% vs 11% (p < 0.001; mean difference 14% [95% CI 9-18]; p < 0.001), with 14% less progression and 18% more albuminuria regression (p < 0.001) than in participants on placebo. End-stage renal event frequency was similar (n = 21 vs 26, p = 0.48). CONCLUSIONS/INTERPRETATION: Fenofibrate reduced albuminuria and slowed estimated GFR loss over 5 years, despite initially and reversibly increasing plasma creatinine. Fenofibrate may delay albuminuria and GFR impairment in type 2 diabetes patients. Confirmatory studies are merited. TRIAL REGISTRATION: ISRCTN64783481.

Estimated glomerular filtration rate and albuminuria are independent predictors of cardiovascular events and death in type 2 diabetes mellitus: the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study.

AIMS/HYPOTHESIS: We investigated effects of renal function and albuminuria on cardiovascular outcomes in 9,795 low-risk patients with diabetes in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study. METHODS: Baseline and year 2 renal status were examined in relation to clinical and biochemical characteristics. Outcomes included total cardiovascular disease (CVD), cardiac and non-cardiac death over 5 years. RESULTS: Lower estimated GFR (eGFR) vs eGFR ≥90 ml min⁻¹ 1.73 m⁻² was a risk factor for total CVD events: (HR [95% CI] 1.14 [1.01-1.29] for eGFR 60-89 ml min⁻¹ 1.73 m⁻²; 1.59 [1.28-1.98] for eGFR 30-59 ml min⁻¹ 1.73 m⁻²; p < 0.001; adjusted for other characteristics). Albuminuria increased CVD risk, with microalbuminuria and macroalbuminuria increasing total CVD (HR 1.25 [1.01-1.54] and 1.19 [0.76-1.85], respectively; p = 0.001 for trend) when eGFR ≥90 ml min⁻¹ 1.73 m⁻². CVD risk was further modified by renal status changes over the first 2 years. In multivariable analysis, 77% of the effect of eGFR and 81% of the effect of albumin:creatinine ratio were accounted for by other variables, principally low HDL-cholesterol and elevated blood pressure. CONCLUSIONS/INTERPRETATION: Reduced eGFR and albuminuria are independent risk factors for cardiovascular events and mortality rates in a low-risk population of mainly European ancestry. While their independent contributions to CVD risk appear small when other risk factors are considered, they remain excellent surrogate markers in clinical practice because they capture risk related to a number of other characteristics. Therefore, both should be considered when assessing prognosis and treatment strategies in patients with diabetes, and both should be included in risk models.

Glycated haemoglobin and cardiovascular outcomes in people with Type 2 diabetes: a large prospective cohort study.

AIMS: To investigate the association between long-term glycaemic control, measured by glycated haemoglobin (HbA(1c)), and time to first cardiovascular disease (CVD) event for people with Type 2 diabetes in New Zealand. METHODS: A prospective cohort study including people with Type 2 diabetes but no previous CVD. The primary outcome measure was time to first recorded fatal or non-fatal CVD event (ischaemic heart disease, cerebrovascular accident, transient ischaemic attack or peripheral vascular disease) as identified from linked primary care, hospital and mortality records between January 2000 and December 2005. A Cox proportional hazards model was used to examine the association between HbA(1c) and time to CVD event, adjusting for age at diagnosis, duration of diabetes, gender, ethnicity, socio-economic status, smoking, blood pressure (BP), serum total cholesterol : high-density lipoprotein ratio, body mass index (BMI) and urine albumin : creatinine ratio. RESULTS: Participants included 48 444 people with Type 2 diabetes. Fifty-one per cent (n = 24 721) were women, median age 60 years. Median duration of diabetes was 3 years, median BMI 31 kg/m(2), median HbA(1c) 7.1% and mean BP was 138/81 mmHg. During the study period (median follow-up 2.4 years), there were 5667 first CVD events (11.7% of cohort). Each 1% increase in HbA(1c) was associated with an increase in hazard ratio (HR) for CVD of 1.08 (95% confidence interval 1.06-1.10, P < 0.001), myocardial infarction [HR 1.08 (1.04, 1.11)] and stroke [HR 1.09 (1.04, 1.13)]. CONCLUSION: This study has confirmed in a large prospective cohort that increased HbA(1c) is an independent risk factor for cardiovascular disease after controlling for traditional risk factors.

An association between ethnicity and cardiovascular outcomes for people with Type 2 diabetes in New Zealand.

AIMS: To investigate the association between ethnicity and risk of first cardiovascular (CV) event for people with Type 2 diabetes in New Zealand. METHODS: A prospective cohort study using routinely collected data from a national primary health care diabetes annual review programme linked to national hospital admission and mortality data. Ethnicity was recorded as European, Maori, Pacific, Indo-Asian, East-Asian or Other. A Cox proportional hazards model was used to investigate factors associated with first CV event. Data was collected from 48,444 patients with Type 2 diabetes, with first data collected between 1 January 2000 and 20 December 2005, no previous cardiovascular event at entry and with complete measurements. Risk factors included ethnicity, gender, socio-economic status, body mass index, smoking, age at diagnosis, duration of diabetes, systolic blood pressure, serum lipids, glycated haemoglobin and urine albumin : creatinine ratio. The main outcome measures were time to first fatal or non-fatal CV event. RESULTS: Median follow-up was 2.4 years. Using combined European and Other ethnicities as a reference, hazard ratios for first CV event were 1.30 for Maori (95% confidence interval 1.19-1.41), 1.04 for Pacific (0.95-1.13), 1.06 for Indo-Asian (0.91-1.24) and 0.73 for East-Asian (0.62-0.85) after controlling for all other risk factors. CONCLUSIONS: Ethnicity was independently associated with time to first CV event in people with Type 2 diabetes. Maori were at 30% higher risk of first CV event and East-Asian 27% lower risk compared with European/Other, with no significant difference in risk for Pacific and Indo-Asian peoples.

An unusual cause of hyperinsulinaemic hypoglycaemia syndrome.

Endogenous hyperinsulinism as a cause for hypoglycaemia can be attributed to a number of different causes including insulinoma, sulphonylurea drugs and the newly described disorder non-insulinoma pancreatogenous hypoglycaemia (NIPH). The calcium stimulation test is increasingly used as a method for not only localizing insulinoma but also for distinguishing the above entities. We describe a case in which felonious sulphonylurea administration was used to mimic either an insulinoma or NIPH. Importantly, this case demonstrates that, contrary to previous reports, the insulin response to calcium stimulation in such cases may be uniformly positive and should alert the physician to possible surreptitious sulphonylurea ingestion.

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 development of a national agreed minimum diabetes dataset for New Zealand.

The development of a minimum diabetes dataset (MDD) for monitoring diabetes in New Zealand was intended to facilitate diabetes quality initiatives. Existing published datasets were reviewed and a draft MDD for New Zealand was distributed to all 147 specialist, general practice and relevant community groups. Data definitions were either identical or compatible with other datasets and dataset items included if there were at least six supportive replies. All groups were followed up by letter and telephone. A total of 26 (18%) replies were received. Comments were reviewed and the recommended MDD finalised. There was agreement that this dataset would be embedded into the software of at least three commercially available patient management systems. In conclusion, developling an agreed national MDD was difficult, in spite of its potential utility for local, regional and national collation of diabetes data allowing those involved to generate a picture of diabetes and its outcomes.

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.

Outcome of pregnancy in patients with insulin-dependent diabetes mellitus and nephropathy with moderate renal impairment.

This study examines the effect of pregnancy on fetal outcome and maternal renal function in 17 women with Type 1 diabetes mellitus and nephropathy attending a joint diabetic-antenatal clinic between 1985 and 1993. There were 7 successful pregnancies in 6 women with moderate renal impairment, mean pre-pregnancy serum creatinine 165 mumol l-1 (Group 1), and 12 in 11 women with proteinuria and preserved renal function (Group 2). Median gestation of pregnancy was 31 + 3 weeks in Group 1 and 36 + 4 weeks in Group 2 (p < 0.05). All babies in Group 1 required neonatal intensive care for a median of 19 days (range 8-271) as compared to only 5 of 13 in Group 2 whose median stay was 13 (7-17) days (p < 0.05). There was one late death in Group 1. Longitudinal creatinine data in those with moderate renal impairment suggest no systematic adverse long-term effect of pregnancy on maternal renal function, although differing changes in renal function were observed during pregnancy. The generally favourable outcome achieved relied heavily upon neonatal care expertise.

Presentation, clinical features and outcome in different patterns of atherosclerotic renovascular disease.

Atherosclerotic renovascular disease (ARD) is an increasingly important cause of renal failure. However, important features of the clinical presentation are not fully described, and the outcome after intervention by angioplasty remains controversial. Ninety-four patients with ARD diagnosed at angiography were reviewed. Twenty-four patients were diabetic. Thirty-nine patients had unilateral renal artery stenosis or occlusion (group A), 28 had bilateral stenosis (group B), and 27 had unilateral occlusion plus contralateral occlusion or stenosis (group C). Two years after presentation, actuarial patient survival was 96%, 74.3% and 47.1% in groups A, B and C, respectively (p < 0.001 for all differences); actuarial renal survival in surviving patients was 97.3%, 82.4% and 44.7%, respectively (p < 0.001 for all differences). Percutaneous transluminal balloon angioplasty (PCTA) was performed in 74 patients. Renal function improved in only a minority of cases, but was stable in 73% of nondiabetic patients 12 months after PCTA. Angioplasty was less effective in diabetic subjects, with only 53.3% having stable renal function at 12 months follow-up. Renal and patient survival were strongly related to the initial angiographic findings. In non-diabetic subjects, PCTA resulted in stabilization of renal function for at least one year in nearly three-quarters of cases, which suggests a benefit from intervention in this disease whose natural history is otherwise of progression.

Blood pressure, diet and the progression of nephropathy in patients with type 1 diabetes and hypertension.

To examine the relationships between the normal dietary intakes of protein and phosphate, blood pressure, and the progression of diabetic nephropathy, we prospectively studied 20 Type 1 diabetic subjects of mean age 43 +/- 10 years (SD) with early nephropathy (mean serum creatinine 115 +/- 43 mumol l-1) over 1 year. Three-monthly measurements of blood pressure, glycaemic control, and normal dietary intake (3-day weighed food records) and 6-monthly measurements of glomerular filtration rate (using a single injection of chromium 51-EDTA) were made. GFR changed at a median rate of -0.89 ml min-1 1.73 m-2 month-1 (range +0.85 to -2.55 ml min-1 1.73 m-2 month-1). Mean dietary protein intake (1.22 g kg-1; range 0.78 to 1.55 g kg-1) and phosphate intake (21.5 mg kg-1; range 14.1 to 30.4 mg kg-1) were not significantly related to the rate of change in GFR. Only mean systolic blood pressure was significantly related to change in GFR, and accounted for 45% of the variability in GFR decline in the 18 subjects who completed the study (r = 0.67; R2 = 0.449; F1,16 = 13.2; p < 0.005; 95% confidence interval for r: 0.336-0.867). A mean systolic blood pressure of 140 mmHg or below was associated with no significant decline in GFR over a median period of 13 months.(ABSTRACT TRUNCATED AT 250 WORDS)

Erythromycin induces supranormal gall bladder contraction in diabetic autonomic neuropathy.

Gall bladder motor function is impaired in some patients with diabetes. It has been suggested that the abnormalities of gall bladder motility are confined to those patients with autonomic neuropathy. Erythromycin, a motilin receptor agonist, causes gall bladder contraction in both normal subjects and patients with gall stones with impaired gall bladder emptying. The effect of erythromycin on gall bladder motility in seven patients with diabetes with an autonomic neuropathy, six patients with diabetes without autonomic neuropathy, and 17 normal subjects was studied using ultrasound. There was no significant difference in gall bladder fasting volume between the three groups, but the patients with diabetes with autonomic neuropathy had impaired postprandial gall bladder emptying compared with normal subjects (percentage emptied (SEM) 40 (10.3)% v 64 (2.8)%, p < 0.01) and those with autonomic neuropathy (48 (7.7)%, NS). Erythromycin produced a dramatic reduction in gall bladder fasting volume in patients with diabetes with an autonomic neuropathy, compared with either normal subjects or patients with diabetes without autonomic neuropathy (percentage reduction 62 (4.6)% in patients with autonomic neuropathy, v 37 (17.6)% in those without autonomic neuropathy, and 26 (7.3)% in the normal subjects, (p < 0.02) and returned gall bladder emptying to normal in all patients with impaired emptying. The pronounced effect of erythromycin in diabetic autonomic neuropathy suggests denervation supersensitivity and that the action of erythromycin on the gall bladder is neurally modulated.