Marie-France Kong

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 subjects 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.

Use of Highly Purified Synthetic Calcium Sulfate Impregnated With Antibiotics for the Management of Diabetic Foot Ulcers Complicated by Osteomyelitis

Diabetic foot osteomyelitis can be managed medically with systemic antibiotics alone or surgically by removing infected bone (1,2). Localized delivery of antibiotics directly to the bone offers a way to achieve an optimal concentration of chosen antibiotics at the site of infection. Antibiotics have been delivered directly into wounds using various vehicles, such as methyl methacrylate and absorbable antibiotic-impregnated gauze, in other clinical settings (3). Highly purified synthetic (HPS) calcium sulfate–based antibiotic therapy offers advantages of being biodegradable, having predictable elution characteristics to deliver antibiotics in concentrations far exceeding the minimum inhibitory concentration of the infecting organism, and having an ability to fill dead space (4,5). We report our experience of using HPS calcium sulfate impregnated with vancomycin and gentamicin in the management of …

The Addison's disease dilemma—autoimmune or ALD?

In September, 2005, a 32-year-old man was referred to us for investigation of a second unprovoked generalised tonic-clonic epileptic seizure that had occurred 2 months earlier. He was found incidentally to have a spastic paraparesis. His fi rst seizure occurred in 1991 (inves tigated and discharged from medical care). His mother had previously been diagnosed with multiple sclerosis causing a mild spastic paraparesis. She had also been diagnosed with idiopathic generalised epilepsy. MRI of the cervical and thoracic spinal cord appeared normal but there were areas of diff use high signal intensity in the occipital white matter of both cerebral hemispheres (fi gure). EEG suggested idiopathic generalised epilepsy. Because of the MRI appearances, a diagnosis of multiple sclerosis was considered and a lumbar puncture was done. The patient started vomiting, complained of a severe headache, and became hypotensive after the lumbar puncture. His serum sodium concentration was initially normal but fell to 105 mmol/L after the procedure. His serum potassium was 3∙3 mmol/L with normal urea and creatinine concentrations. An endocrine opinion was sought. Generalised pigmentation was noted. The patient was treated for addisonian crisis (serum cortisol came back at 125 nmol/L; corticotropin 1250 ng/L). In light of his adrenal failure, pyramidaltract signs, and MRI evidence of cerebral leucodystrophy, a diagnosis of X-linked adrenoleucodystrophy (ALD) was made. This was subsequently confi rmed biochemically by assay of very-long-chain fatty acids (VLCFA). Our patient’s epileptic seizures were concluded to be unrelated to the ALD. Incidentally, he was also found to be biochemically hypothyroid, with positive thyroid peroxidase antibody; there were no adrenal, parietal cell, or intrinsic factor antibodies. His Lancet 2008; 371: 1970

Altered mental state and the Whipple triad

A 47-year-old man presented with episodes of altered mental state initially felt to be complex partial seizures, but which were in fact hypoglycaemic episodes. An insulinoma was confirmed and eventually localised. He underwent an abdominal computed tomography scan and intraoperative laparoscopy, but required selective venous sampling to localise the tumour. Fifteen months after his surgery there is no evidence of recurrence of his insulinoma.

A swollen knee: and the father of hysteria

In July, 2006, a 69-year-old woman was in our foot clinic, when she mentioned that her right knee had been painful and swollen for 2 months. The swelling had gradually increased; the patient recalled no injury. Her type 2 diabetes was poorly controlled: we saw her regularly in the foot clinic for a neuropathic ulcer, which was healing slowly; she had had several laser treatments for bilateral diabetic maculopathy. The knee was hot and swollen; its range of movement was limited by pain. Her other joints were normal. Her knee and ankle refl exes were absent—as we had observed previously—and she had reduced sensation to pain, touch, vibration, and temperature in both feet: these fi ndings were consistent with neuropathy. We suspected osteoarthritis. However, blood tests showed a white-cell count of 13∙4×109 cells per L, and a C-reactive-protein concentration of 128 mg/L. Radiography showed destruction and lucent defects of the right tibial plateau, and reduction of the medial and lateral compartments of the tibiofemoral joint (fi gure). These fi ndings were consistent with erosive arthropathy or septic arthritis. Microscopy and culture of a knee aspirate showed no bacteria or crystals, so we ruled out sepsis, gout, and pseudogout as possible causes of the swelling. CT showed bone destruction in the proximal tibia. We diagnosed a Charcot knee. We gave the patient conservative treatment, immobilising the knee in a Genurange (Medi UK, Hereford, UK) cast. When the patient was last seen, in June, 2008, the swelling was reduced; she was still wearing the brace during the day, and was mobilising with a Zimmer frame. The Charcot joint is a relatively painless, progressive arthropathy caused by a neurological defi cit. In 1868, Jean-Martin Charcot, famous for his descriptions of hysteria, gave the fi rst detailed account of neuropathic joint damage caused by syphilis. His patient, who had tabes dorsalis, had increasing swelling and instability of the knees; the joints were severely deformed. In 1936, Jordan attributed Charcot joints to diabetes, which is now thought to be the most common cause. Nonetheless, Charcot arthropathy is found in only around 1% of people with diabetic neuropathy. The factors that predispose to its development are unknown. Most commonly, it aff ects the ankle joint and the forefoot: damage to the knee is rare. Acute infl ammation, characterised by hyperaemia, is self-limiting, and succeeded by re-ossifi cation. Initial fi ndings on radiography can be unremarkable, or resemble those in osteoarthritis. Further imaging with CT, MRI, or isotope bone scanning may be necessary. Charcot joints should be immobilised early, to prevent further joint destruction. Since the knee bears the weight of the body, and has little surrounding soft tissue for stabilisation, it is especially susceptible to progressive destruction and instability. The knee should be given protective bracing for 6–18 months, to provide stability and reduce shear stresses across the joint. Bisphosphonates have been used to reduce osteoclast activity. If bracing fails to provide stability, arthrodesis has been recommended (with reasonable success), rather than internal fi xation or joint replacement. The disease must be in a quiescent phase for successful union to occur. Total joint arthroplasty of the neuropathic knee is controversial, and should be reserved for (usually severely deformed) unstable joints or fractures, because the potential complications are many: risks include fracture, and dislocation of parts of the femoral or tibial prosthesis. Total joint arthroplasty has been done in a few cases, but only when conservative treatment has failed, and arthroplasty has been the only viable option.

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.

Progressive cerebellar ataxia and new-onset diabetes

In October, 2012, a 37-year-old Rwandan businessman was transferred to our hospital from Nairobi, Kenya, where he had been investigated for subacute onset of progressive cerebellar ataxia and quadriparesis of unclear cause. He presented initially to a hospital in Nairobi in August, 2012, with a 2–3 week history of imbalance and weakness, as well as back pain and stiff ness, without cognitive or systemic symptoms. He had no history of preceding infection or vaccination and the only recent travel had been to Dubai and Europe. Over the following 6 weeks his symptoms progressed and he became more unsteady on his feet, and unable to stand without support. He developed speech diffi culty with mild dysphagia, and reported blurred vision. On examination at our hospital, he had noticeable cerebellar dysarthria, appendicular cerebellar signs, and pronounced truncal ataxia. Limb motor strength and sensation were normal. He had no diplopia and no nystagmus. Hypertropia, convergence insuffi ciency, and hypometric and slow saccades, especially in the upward gaze, were present, suggesting brainstem involvement. Cognition was normal. MRI of brain and spine was normal apart from a few non-specifi c small white matter hyperintensities. Nerve conduction studies and electro-myography were normal. Detailed laboratory profi le was normal apart from fasting blood glucose of 8·6 mmol/L. Lumbar puncture revealed a raised IgG index and the presence of oligoclonal IgG bands. CSF protein and cytology were normal. A paraneoplastic syndrome was considered but investi gations were negative. FDG-PET revealed a depressed glucose metabolism in the cerebellum and in the right thalamus (fi gure). Immunoblotting for diagnosis of antineuronal antibodies was negative. A repeat fasting glucose of 9·0 mmol/L confi rmed diabetes and the patient was started on metformin. He had no family history of diabetes or of autoimmune diseases. Autoantibodies to glutamic acid decarboxylase (GAD-ab) were checked: the concentration was very high (> 250 IU/mL). Islet cell antibodies (ICA) were positive at a titre of 25 600. Other autoantibodies were negative.A diagnosis of autoimmune cerebellar ataxia was suspected and confi rmed by the presence of high titres of GAD-ab in the CSF. The patient was treated with high doses of steroids and pulses of intravenous cyclo-phosphamide. Although there was a diminution in the serum GAD-ab titres, improvement in symptoms after 9 months was minimal (the patient was last seen in July, 2013, when he returned to Nairobi). Follow-up MRI brain scan did not show any changes, in particular no cerebellar atrophy. 9 months after diagnosis of his diabetes his blood sugars remain well controlled on metformin only.Autoimmune cerebellar ataxia related to GAD-ab is a rare condition that typically aff ects women with late-onset type 1 diabetes or other autoimmune disorders.

LeucoPatch system for the management of hard-to-heal diabetic foot ulcers in the UK, Denmark, and Sweden: an observer-masked, randomised controlled trial.

BACKGROUND The LeucoPatch device uses bedside centrifugation without additional reagents to generate a disc comprising autologous leucocytes, platelets, and fibrin, which is applied to the surface of the wound. We aimed to test the effectiveness of LeucoPatch on the healing of hard-to-heal foot ulcers in people with diabetes. METHODS This was a multicentre, international, observer-masked, randomised controlled trial of people with diabetes and a hard-to-heal foot ulcer done in 32 specialist diabetic foot clinics in three countries (UK, Denmark, and Sweden). After a 4-week run-in period, those with a reduction in ulcer area of less than 50% were randomly allocated (1:1) by computer-generated, web-based randomisation (block sizes of two, four, and six) to either prespecified good standard care alone or care plus weekly application of LeucoPatch. The primary outcome was the proportion of ulcers that healed within 20 weeks assessed in the intention-to-treat population (all participants with post-randomisation data collected), defined as complete epithelialisation (confirmed by an observer who was masked to randomisation group), and remained healed for 4 weeks. This trial is registered with the ISRCTN registry, number 27665670, and ClinicalTrials.gov, number NCT02224742. FINDINGS Between Aug 30, 2013, and May 3, 2017, 269 participants were randomly allocated to receive treatment (137 to receive standard care and 132 to receive LeucoPatch). The mean age was 61·9 years (SD 11·6), 217 (82%) were men, and 222 (83%) had type 2 diabetes. In the LeucoPatch group, 45 (34%) of 132 ulcers healed within 20 weeks versus 29 (22%) of 134 ulcers in the standard care group (odds ratio 1·58, 96% CI 1·04-2·40; p=0·0235) by intention-to-treat analysis. Time to healing was shorter in the LeucoPatch group (p=0·0246) than in the standard care group. No difference in adverse events was seen between the groups. The most common serious adverse event (SAE) was diabetic foot infection (24 events in the LeucoPatch group [24% of all SAEs] and 20 in the standard care group [27% of all SAEs]. There were no device-related adverse events. INTERPRETATION The use of LeucoPatch is associated with significant enhancement of healing of hard-to-heal foot ulcers in people with diabetes. FUNDING Reapplix ApS.

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 Wilsons 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.

Weight loss and nausea in a patient taking digoxin

In August 2007, a 76 year old white woman was referred because of a two week history of worsening lethargy with loss of appetite and nausea. She had ischaemic heart disease and hypertension and had had a pacemaker inserted in February 2007 for atrial fibrillation with sinus pauses. She had lost 9.3 kg in the past 10 months. When she visited her family doctor two days before hospital admission her symptoms were initially thought to be caused by digoxin toxicity (digoxin concentration 5 nmol/L, therapeutic range 0.9-2.6), so her digoxin dose had been reduced, but a random blood glucose measurement was raised at 29.3 mmol/L (reference range 3.3-6.0) and she was referred to hospital. She had been diagnosed with type 2 diabetes in February 2006 on an oral glucose tolerance test (0 min blood glucose 5.1 mmol/L, 2 hour value 12.3 mmol/L) and had been controlled using diet alone. Her glycated haemoglobin (HbA1c) value had been 6.4% (4.0-6.1%; 46 mmol/mol, 20-43) in February 2007. She was thin, weighing 45 kg, with a body mass index of 17. Her breath smelled “fruity.” Her blood pressure was 148/89 mm Hg. Urinalysis showed 3+ glucose and 3+ ketones. Arterial pH was 7.241 (7.35-7.45), bicarbonate 12 mmol/L (22-29), sodium 129 mmol/L (133-146), potassium 4.9 mmol/L (3.5-5.3), urea 29.3 mmol/L (2.5-7.8), creatinine 213 µmol/L (60-120), and blood glucose 59.3 mmol/L (3.3-6.0). Haemoglobin was 145 g/L (115-165), white cell count was 12.1×109/L (4.0-11.0), and platelets were 251×109/L (140-400). ### 1 What is the diagnosis? #### Short answer Diabetic ketoacidosis (DKA). #### Long answer DKA consists of the biochemical triad of ketonaemia (≥3 mmol/L) or severe ketonuria (more than 2+ on standard urine sticks), hyperglycaemia (blood glucose >11 …