Charcot neuroarthropathy of the knee in Type 1 diabetes: treatment with total knee arthroplasty.

BACKGROUND: Charcot neuroarthropathy is well recognized in diabetes, although it typically affects the joints of the forefoot and ankle. Neuroarthropathy affecting the knee in diabetes is extremely rare. The surgical options for treatment of Charcot neuroarthropathy remain poorly defined, particularly the use of arthroplasty with knee involvement. METHODS: We describe a case of neuroarthropathy of the knee in a patient with Type 1 diabetes. We also describe the successful management of the disorder with total knee arthroplasty-only the third such description. RESULTS: The case illustrates some of the typical radiological features of this uncommon condition, which may aid early diagnosis and limit morbidity.

A 'fail-safe' screening programme for diabetic retinopathy.

OBJECTIVE: To improve screening for diabetic retinopathy in a hospital diabetic clinic through the use of the audit process. DESIGN: Comparison of an existing system of screening for diabetic retinopathy (a specialist optometrist using ophthalmoscopy alone) with a new system in which a specialist optometrist examined retinal Polaroid photographs taken through pharmacologically dilated pupils and combined this with ophthalmoscopy in all cases except when the photographs were perfect and definitely showed no retinopathy. In this new system, the optometrist could discuss cases of uncertainty with a diabetes physician while the patient was still in the clinic with eyes dilated. SETTING: Inner city hospital diabetes clinic. SUBJECTS: 289 hospital diabetic clinic patients not already attending an ophthalmologist; a consecutive series of 144 such patients for the first audit, 145 for the repeat audit. MAIN OUTCOME MEASURES: Assessment of each screening system against a gold standard. For the first audit this was agreement by two of four diabetes physicians, who combined examination of the photographs with the findings from dilated ophthalmoscopy, on the classification of the retinae of each patient, guided by standard European criteria. For the second audit, the gold standard was enhanced by discussing the photographs and findings of all patients with an independent ophthalmologist. For patients requiring referral, a second ophthalmologist also commented on the case. RESULTS: The addition of retinal photography to universal pupil dilatation, and the availability of diabetes physician backup to discuss cases of uncertainty, greatly increased the optometrists' detection rate. Sensitivities for the first (ophthalmoscopy only) and second (ophthalmoscopy plus photography plus diabetologist back-up) audits were, respectively, 71.4% vs 100% for sight-threatening retinopathy, 33% vs 100% for retinopathy requiring six-month review, and 40.3% vs 97.2% for any retinopathy (p = 0.002). CONCLUSIONS: Optometrists specialising in diabetic retinopathy using Polaroid retinal photography and ophthalmoscopy, both through dilated pupils, backed up by experienced diabetologists to discuss cases of uncertainty, could form the basis of a retinopathy screening service that accurately identifies and categorises retinopathy and does not miss sight-threatening cases.

Diabetes care in South Asian and white European patients with type 2 diabetes.

Aspects of diabetes care in South Asian and white European patients with Type 2 diabetes attending a hospital review clinic were explored. Among the clinic population of 1710 patients, 258 (15%) were of South Asian origin. A significantly greater proportion (95% CI for difference in proportions 8-22%) of these patients was treated with oral hypoglycaemic drugs than in white Europeans, in whom there was a correspondingly greater proportion receiving insulin treatment. In a case-control study, where 154 patients in each racial group were stratified according to treatment regimen, significantly more South Asian patients (13/30 vs 6/30, p < 0.05) on insulin were treated with a once-daily regimen. Despite these observed differences in treatment of diabetes, glycaemic control was no worse in South Asian patients when compared to their white European counterparts. South Asian diabetic patients attending hospital diabetes clinics in the UK can experience similar levels of glycaemic control to white Europeans.

Organized chaos? Computed tomographic evaluation of the neuropathic diabetic foot.

Accurate radiographic evaluation of diabetic neuroarthropathy is increasingly difficult as the disease becomes more florid. 22 patients with a known diabetic neuroarthropathy of one or both feet were prospectively examined by computed tomography (CT) in the axial and coronal planes. Bilateral changes of a neuroarthropathy were present in 75% of cases. Distinct patterns of disease were seen and categorized into five types in order of increasing severity. Changes at the medial tarsometatarsal joints and adjacent intercuneiform joints were seen in all affected feet. More extensive disease involved the medial arch more commonly than the lateral. Fractures of the tarsal bones were found in 32% of cases and were associated with neuroarthropathic changes in adjacent joints. Calcaneal fractures were seen in four feet. A Lisfranc fracture-dislocation was present in 41% of cases and a bilateral in only 21%. A single CT examination of the foot, while an accurate method of demonstrating the extent of the disease, is an insensitive indicator of disease activity.

ACTH-independent Cushing's syndrome in pregnancy with spontaneous resolution after delivery: control of the hypercortisolism with metyrapone.

A 25-year-old primigravid woman presented with Cushing's syndrome at 23 weeks gestation; serum cortisol was 1090 nmol/l at 0900 h, 1230 nmol/l at 2200 h; basal urinary free cortisol excretion was 3680 nmol/24 h, and 8830 nmol/24 h after dexamethasone 8 mg daily for 48 hours; plasma ACTH was < 1.1 pmol/l. CT scan of the adrenal glands showed bilateral adrenal hyperplasia. The hypercortisolism was controlled with metyrapone until elective delivery of the fetus by Caesarean section at 34 weeks gestation because of a decline in growth. No adverse fetal effects of metyrapone treatment were apparent, maternal outcome was uncomplicated and wound healing was unimpaired. Maternal adrenocortical function had returned to normal within 4 weeks of the cessation of pregnancy and biochemical remission has been maintained up to 9 months post-partum. Metyrapone therapy is effective in controlling the hypercortisolism in certain cases of Cushing's syndrome complicating pregnancy.

Persisting mortality in diabetic ketoacidosis.

An overall hospital mortality rate of 3.9% was found in 929 episodes of diabetic ketoacidosis treated in single centre over a 21-year period. The mortality rate in the first half of the survey (4.4%) was not significantly different from that in the second half of the survey (3.4%). Six deaths in patients under 50 years of age occurred in the first half, but only one death under 50 years occurred in the second half of the survey. The number of deaths from a metabolic cause where no other illness was identified also fell from nine (43% of deaths) in the first half to five (33% of deaths) in the second half of the study (not significant). The remaining deaths were due to concurrent illness, mainly myocardial infarction and serious infections. Many of the residual deaths occurred in elderly patients with such medical illness in addition to the ketoacidosis. It may, therefore, prove difficult to reduce mortality further in diabetic ketoacidosis.

Euglycaemic diabetic ketoacidosis: does it exist?

The original criteria described for euglycaemic ketoacidosis (initial blood glucose less than 16.7 mmol/l and plasma bicarbonate equal to or less than 10 mmol/l) were identified in 23 of 722 consecutive episodes (3.2%) of diabetic ketoacidosis. True euglycaemic ketoacidosis (initial blood glucose 10 mmol/l or less) was rare, occurring in 0.8-1.1% of all episodes depending on the defining plasma bicarbonate concentration. Management of euglycaemic ketoacidosis with low-dose continuous intravenous infusion of insulin together with adequate fluid replacement was effective. The clinical and biochemical data did not support the concept of euglycaemic ketoacidosis as a separate entity. The importance of ketone testing rather than glucose testing in the diagnosis of ketoacidosis is, however, emphasized. The importance of adequate insulin and fluid therapy in those few episodes where blood glucose is normal or near normal at presentation is also highlighted.

Impotence in diabetes: aetiology, implications for treatment and preferred vacuum device.

In an assessment of the contributions of autonomic neuropathy and vascular disease to the aetiology of male impotence in diabetes, evidence of autonomic neuropathy was identified in 23/39 (59%) individuals complaining of impotence. Thirteen of 26 men aged < 60 years tested with an intracorporeal injection of papaverine experienced little or no response and seven had tumescence but no rigidity. Radioisotope phallography demonstrated vascular disease in six of these seven, suggesting evidence of a vascular component in 19/26 (73%). Only one patient had non-organic impotence. Overall, evidence of vascular disease alone was demonstrated in 10/26 (38%), vascular disease plus autonomic neuropathy in 9/26 (35%), and autonomic neuropathy alone in 6/26 (23%). Many diabetic men complaining of impotence appear to have a significant vascular component which renders intracorporeal papaverine treatment ineffective. We compared the performance of a vacuum constriction-band (Erecaid) and condom-type (Synergist) device in 10 randomly selected men from this group. The devices, provided in random order for 5 months each, were assessed by questionnaire and interview of both the patient and partner. Two couples defaulted and another could use neither device. Although erectile capacity could be restored in the remainder, subsequent intercourse was only deemed satisfactory to both partners in five couples, who unanimously preferred the constriction-band device. In treatment with vacuum devices the constriction-band type seems to be the device of choice; the condom type should probably be reserved for those unable to use the constriction-band type.

Glomerular structure in type-1 (insulin-dependent) diabetic patients with normo- and microalbuminuria.

Kidney biopsies from 15 type-1 (insulin-dependent) diabetic patients with a range of albumin excretion (AER) were analyzed. Nine patients had normal AER, and six had microalbuminuria. Basement membrane thickness, BMT, and mesangial matrix volume fraction, Vv(mat/glom), were obtained from at least three glomeruli per biopsy. Mesangial structures were estimated with electron microscopic analysis at three levels in each glomerulus. Glomerulopathy parameters were significantly increased in micro- versus normoalbuminuric patients with the following means and (CV): BMT 571 nm (0.12) and 442 nm (0.25), P = 0.03; Vv(mes/glom) 0.31 (0.20) and 0.22 (0.14), P = 0.002; Vv(matrix/glom) 0.17 (0.25) and 0.11 (0.28), P = 0.006; matrix star volume 56 microns 3 (0.47) and 22 microns 3 (0.43), P = 0.02. A positive correlation obtained between AER and each of the glomerulopathy parameters, BM thickness, Vv(mes/glom) and Vv(matrix/glom), as well as between AER and a structural index expressing the sum of changes in the peripheral BM and in the mesangium (r = 0.62, P = 0.01). The results indicated a parallel course of mesangial and peripheral BM changes: a positive correlation obtained between BM thickness and mesangial parameters [BMT versus Vv(matrix/glom): r = 0.82, P = 0.0001] and the ratio of the two subsets of glomerular BM material (PBM:matrix) did not show significant difference between normo- and microalbuminuric groups. The data give strong support to the contention that the transition from normo- into the microalbuminuric phase is linked to progressing glomerulopathy.

Investigation of selected patients with hypertension by the rapid-sequence intravenous urogram.

The rapid-sequence intravenous urogram (IVU) has tended to fall from favour for investigating hypertension because of its perceived imprecision for detecting renovascular disease. However, no study has examined the value of the IVU as a screening test in appropriately selected patients. We have analysed the diagnostic yield of the rapid-sequence IVU in hypertensive patients selected for features suggesting renal or renovascular disease in a retrospective review of case records from a hypertension clinic. The IVU was abnormal in 27% (95% CI 21-32%) of 241 consecutive patients. The most common abnormalities were chronic pyelonephritis (6%); proven renovascular disease (5%); stone (4%); possible renovascular disease and simple cyst (each 3%); hydronephrosis (2%); and tumour and active tuberculosis (each 1%). The IVU led to intervention aiming to correct hypertension in 5% (95% CI 2-8%) of patients, and revealed an abnormality needing intervention in its own right in 4% (95% CI 2-6%). The IVU led to unnecessary invasive investigation in 3% of cases. Individual abnormalities could not be predicted from the clinical or laboratory features. The initial investigation in hypertensive patients with suspected renal or renovascular disease should be a general purpose test able to detect a wide range of abnormalities. The rapid-sequence IVU is the only single test capable of satisfying this requirement. In patients with features suggesting renovascular disease, a normal rapid-sequence IVU excludes renovascular disease with 93% probability, but is an imperfect screening test since it fails to diagnose about 20% of cases. Renal arteriography should be done despite a normal IVU when it is essential to exclude renovascular disease.

The association between haemospermia and severe hypertension.

The association between haemospermia and hypertension was examined in a case-control study comparing 5 hypertensive patients with haemospermia to 20 age-matched hypertensive men. Patients with haemospermia had much higher blood pressures than hypertensive controls (200/131 mmHg vs 147/90 mmHg; P less than 0.0005/P less than 0.0001), higher left ventricular voltage on ECG (P less than 0.02), and higher concentrations of serum creatinine, proteinuria and renovascular disease (all P = 0.06 vs controls). Haemospermia is associated with severe uncontrolled hypertension. It is not, however, associated with hypertension per se, as the prevalence of hypertension in published series of patients with haemospermia is no higher than that expected in the general population. Men presenting with haemospermia should have their blood pressure measured carefully as they may require antihypertensive treatment urgently.

Factors related to treatment resistance in hypertension.

Hypertension which is resistant to treatment carries a relatively bad prognosis. Factors associated with treatment resistance were examined in a case-control study in a hospital hypertension clinic. Patients with resistant hypertension had more severe hypertension and more frequently had evidence of end-organ damage on presentation to the clinic. The prevalence of accelerated phase hypertension, renovascular disease and impaired renal function was also higher in these patients. Cigarette smoking, and the combination of cigarette smoking and heavy caffeine use, were greater in patients with resistant hypertension. Resistant hypertension did not appear to be associated with older age, obesity, regular alcohol use, various psychological factors or non-compliance. These findings support an aggressive investigation policy in resistant hypertension, and underline the harmful effects of cigarette smoking to hypertensive subjects.

Plasma lipid and coagulation factor concentrations in insulin dependent diabetics with microalbuminuria.

OBJECTIVE: To determine whether insulin dependent diabetics with microalbuminuria have significant abnormalities in concentrations of lipoproteins, apolipoproteins AI and B, fibrinogen, and clotting factor VII which could result in increased cardiovascular risk. DESIGN: Case-control study. SETTING: Outpatient department of a metabolic ward. PATIENTS: Group of 20 insulin dependent diabetics with urinary albumin excretion rates greater than 30 micrograms/min (microalbuminuria) and 20 individually matched insulin dependent diabetics with normal urinary albumin excretion rates (below 30 micrograms/min) matched for age, sex, and duration of diabetes. INTERVENTIONS: Fasting venous blood samples were taken for determination of concentrations of glucose, glycated haemoglobin, lipoproteins, apolipoproteins AI and B, fibrinogen, and factor VII. Height, weight, arterial pressure, and usual insulin dose were recorded, and each patient was given a dietary questionnaire to be completed at home. END POINT: Comparison of blood pressure and concentrations of lipoproteins, apolipoproteins AI and B, and fibrinogen in the diabetics with microalbuminuria and the controls. MEASUREMENTS AND MAIN RESULTS: Patients with microalbuminuria had significantly higher concentrations of low density lipoprotein cholesterol (mean 3.33 (SE 0.20) v 2.84 (0.12) mmol/l) and very low density lipoprotein cholesterol (0.30 (0.05) v 0.17 (0.03) mmol/l) than controls but significantly lower concentrations of high density lipoprotein 2 subfraction cholesterol (0.32 (0.04) v 0.54 (0.04) mmol/l). Concentrations of total triglyceride (1.11 (0.14) v 0.68 (0.08) mmol/l), very low density lipoprotein triglyceride (0.56 (0.10) v 0.30 (0.05) mmol/l), apolipoprotein B (0.88 (0.06) v 0.67 (0.03) g/l) and fibrinogen (2.2 (0.1) v 1.9 (0.1) g/l), and diastolic arterial pressure (80 (2) v 74 (2) mm Hg), were also higher in patients with microalbuminuria. CONCLUSIONS: Cardiovascular risk factors--namely, disturbances in lipoprotein and apolipoprotein concentrations, increased fibrinogen concentration, and increased arterial pressure--are already present in insulin dependent diabetics with microalbuminuria. The increased risk of coronary heart disease in patients with clinical proteinuria may result from prolonged exposure to these risk factors, which are present before any impairment of renal function.

The variability of overnight urinary albumin excretion in insulin-dependent diabetic and normal subjects.

The variability of overnight urinary albumin excretion rate (AER) and albumin to creatinine ratio was assessed in eight normal subjects and two groups of insulin-dependent diabetic patients divided on the basis of an initial overnight urinary albumin excretion rate below (n = 15) or above (n = 12) 30 micrograms/min. The latter group is known to be at risk of developing clinical diabetic nephropathy. An albumin to creatinine ratio of 2.6 and above identified all patients with an initial albumin excretion rate greater than 30 micrograms/min. The mean of the coefficients of variation, calculated from five successive overnight urine collections, for all subjects was 38% for albumin excretion rate and 37% for albumin to creatinine ratio. There was no significant difference in the variation of albumin excretion rate and albumin to creatinine ratio within or between the groups. Subsequent AERs from diabetics with an initial rate greater than 30 micrograms/min changed category more often (chi 2 = 11.9, p less than 0.001) than those from diabetics with lower initial rates and normal subjects. This was due to four subjects with initial values close to the cut-off level, whose subsequent values varied around it. Albumin excretion rates in normal subjects never exceeded 11 micrograms/min. Whether a patient's risk status is influenced by the degree of variation of albumin excretion rate around a risk level, or whether the classification of risk is improved by multiple collections, awaits testing in prospective subjects.

Rapid detection of urinary albumin at low concentration by an agglutination inhibition techniqué.

Subclinical elevation of urinary albumin excretion (microalbuminuria) identifies individuals at high risk of developing nephropathy in insulin-dependent diabetes. We have evaluated the performance of a new specific method for the rapid detection of microalbuminuria employing a latex agglutination inhibition technique. A total of 96 consecutive sterile first morning urine samples from insulin-dependent diabetic subjects were tested using AlbuScreen TM (Cambridge Life Sciences). Fifteen samples with albumin concentration greater than 27 micrograms/ml (range 27.6-780 micrograms/ml) read positive with AlbuScreen and were identified with 100% sensitivity and specificity. This test which is ten times more sensitive than the qualitative methods in current use and which detects a wide range of urinary albumin concentrations from microalbuminuria to heavier proteinuria may prove useful in the outpatients setting.