Bilateral posterior ischaemic optic neuropathy after severe diabetic ketoacidosis, cardiopulmonary resuscitation and respiratory failure

A 44-year-old male European with type I diabetes mellitus fell into diabetic ketoacidosis. In the emergency room, he developed an episode of asystole and respiratory failure requiring one cycle of cardiopulmonary resuscitation and extracorporeal membrane oxygenation (ECMO). Waking up 7 days later, he presented a bilateral complete loss of vision. Ophthalmological examination including funduscopy on days 1 and 10, after extubation, showed bilateral large round pupils non-reactive to light and a normal fundus. Neuroimaging studies, including MRI and MRA of the brain, were all within normal limits. A lumbar puncture and comprehensive serological testing excluded an infectious or rheumatic cause. An empirical high-dose intravenous steroid treatment administered for 5 days had no effect on his vision. His eye examination at 1.5 months follow-up showed a normal fundus except for progressive bilateral optic nerve disc pallor, which pointed towards the diagnosis of a posterior ischaemic optic neuropathy.

Preventive effects of octreotide (SMS 201-995) on diabetic ketogenesis during insulin withdrawal

1. Exogenous somatostatin inhibits glucagon secretion and prevents ketoacidosis in diabetic patients, but has the therapeutic disadvantage of requiring continuous intravenous infusion to exhibit these effects. 2. Consequently, we examined the effect of subcutaneous administration of the long-acting somatostatin analogue octreotide (SMS 201-995) on early ketogenesis in diabetic ketoacidosis. On two separate occasions insulin was withdrawn over a period of 9 h from seven type I diabetic patients. On the second occasion the patients were given 50 micrograms octreotide s.c. before the insulin withdrawal and every 3 h during insulin withdrawal. 3. Differences in integrated free fatty acid responses (4706 +/- 1227 mumol l-1 h vs 3026 +/- 835 mumol l-1 h, AUC, P = NS) were not significant, but the peak increments of acetoacetate (1413 +/- 354 mumol l-1 vs 612 +/- 176 mumol l-1, P less than 0.05), beta-hydroxybutyrate (2180 +/- 475 mumol l-1 vs 922 +/- 246 mumol l-1, P less than 0.01) and the decrements in plasma bicarbonate (-8 +/- 1 mumol l-1 vs -4 +/- 1 mumol l-1, P less than 0.05) and pH (-0.07 +/- 0.01 vs -0.03 +/- 0.01, P less than 0.05) were significantly less with octreotide. 4. At the same time peak increments of glucagon were lower with octreotide treatment (329 +/- 206 pg ml-1 vs 39 +/- 30 pg ml-1, P less than 0.05). 5. We conclude that, despite accelerated lipolysis and provision of substrate for ketogenesis during insulin withdrawal, this somatostatin analogue significantly reduces ketogenesis resulting from insulin deprivation, probably secondary to decreasing glucagon secretion. This drug may be useful in short term prophylactic treatment of diabetic patients during periods of increased risk for ketoacidosis.

[Endocrine crises]

Pituitary apoplexy, diabetes insipidus, thyroid storm, myxedema coma, parathyrotoxic crisis, hypocalcemia tetany, pheochromocytoma and Addison crisis, diabetic ketoacidosis, diabetic hyperosmolar nonketotic coma, hypoglycemia and carcinoid crisis are the most important endocrine crises. Some of them are common, others very rare. All physicians nevertheless need to have at least a basic knowledge of all of them, since symptoms and signs of endocrine crises overlap with those of other severe disease states, and the failure to recognise endocrine crises as such and to begin rapidly the specific therapy can have fatal consequences.

Non-acute myocardial infarction-related causes of elevated high-sensitive troponin T in the emergency room: a cross-sectional analysis

To systematically investigate putative causes of non-coronary high-sensitive troponin elevations in patients presenting to a tertiary care emergency department. In this cross-sectional analysis, patients who received serial measurements of high-sensitive troponin T between 1 August 2010 and 31 October 2012 at the Department of Emergency Medicine were included. The following putative causes were considered to be associated with non-acute coronary syndrome-related increases in high-sensitive troponin T: acute pulmonary embolism, renal insufficiency, aortic dissection, heart failure, peri-/myocarditis, strenuous exercise, rhabdomyolysis, cardiotoxic chemotherapy, high-frequency ablation therapy, defibrillator shocks, cardiac infiltrative disorders (e.g., amyloidosis), chest trauma, sepsis, shock, exacerbation of chronic obstructive pulmonary disease, and diabetic ketoacidosis. During the study period a total of 1,573 patients received serial measurements of high-sensitive troponin T. Of these, 175 patients were found to have acute coronary syndrome leaving 1,398 patients for inclusion in the study. In 222 (30 %) of patients, no putative cause described in the literature could be attributed to the elevation in high-sensitive troponin T observed. The most commonly encountered mechanism underlying the troponin T elevation was renal insufficiency that was present in 286 patients (57 %), followed by cerebral ischemia in 95 patients (19 %), trauma in 75 patients (15 %) and heart failure in 41 patients (8 %). Non-acute coronary syndrome-associated elevation of high-sensitive troponin T levels is commonly observed in the emergency department. Renal insufficiency and acute cerebral events are the most common conditions associated with high-sensitive troponin T elevation.

The diabetic child in the emergency room

The WHO announced diabetes mellitus as one of the main threats to human health in the 21st century. In children and adolescents the prevalence of both the autoimmune type 1 and the obesity-related type 2 diabetes is increasing. Common to all types of diabetes is an absolute or relative lack of insulin to keep glucose homeostasis under control. Thus children and adolescents with newly diagnosed diabetes present with hyperglycemia which is often accompanied by ketoacidosis bearing the risk of cerebral edema. Children and adolescents with known diabetes treated with insulin or orale antidiabetic agents may also suffer from hyperglycemia or even ketoacidosis during times of non-compliance with diet and drugs or during concomitant illnesses. Hyperglycemia with ketoacidosis is an emergency situation for which patients need to be admitted to the next hospital for administration of insulin, fluids and potassium. In contrast, insulin treatment in diabetic patients may also lead to a hypoglycemia, the sudden drop in blood glucose, at any moment. Thus recognition and correction of mild hypoglycemia should be familiar to every diabetic child and their caretaker. Severe hypoglycemia with or without seizures may bring the diabetic child in a sudden emergency situation for which the administration of glucagon intramuscularly or glucose intravenously is mandatory. After every severe hypoglycemia the insulin and diet regimen of the diabetic child or adolescent must be reviewed with the diabetes specialist. For unexplained hypoglycemia or major treatment adjustments the diabetic child or adolescent may need to be readmitted to the diabetic ward of a hospital to avoid repeat, potentially life-threatening hypoglycemia.

Insulin increases serum leptin concentrations in children and adolescents with newly diagnosed type I diabetes mellitus with and without ketoacidosis.

AIMS/HYPOTHESIS The aims of this study were to analyse the changes of serum leptin in newly diagnosed children and adolescents with Type I (insulin-dependent) diabetes mellitus after insulin treatment and to examine the possible impact of ketoacidosis on these changes. METHODS Baseline serum leptin concentrations were measured in 28 newly diagnosed Type I diabetic patients [age 8.75 +/- 4.05 years (means +/- SD); BMI 15.79 +/- 2.47 kg/m(2); HbA(1 c) 11.3 +/- 1.9 %] with (n = 18) and without (n = 10) ketoacidosis before commencement of insulin treatment, at the time of diagnosis. Thereafter, during a 4-day course of continuous intravenous insulin injection to gain and maintain euglycaemia, serum leptin concentrations were assessed. RESULTS Baseline serum leptin concentrations, adjusted to age, BMI, sex and pubertal stage, differed among these patients. There was, however, an increase of leptin in all subjects from 1.37 +/- 0.56 ng/ml (mean +/- SD) up to 2.97 +/- 1.52 ng/ml by 117 % (p < 0.0001) after insulin therapy. On average, peak serum leptin concentration was obtained after 42 h of insulin treatment. Further, there was no difference in the mean increase of serum leptin concentrations in the two groups, namely with and without ketoadicosis, of insulin-dependent diabetic children and adolescents. In addition, there was no correlation between serum leptin concentrations and correction of ketoacidosis during insulin treatment. CONCLUSIONS/INTERPRETATION Insulin increases serum leptin, within 1 day, in children and adolescents with newly diagnosed Type I diabetes. Ketoacidosis does not influence this interaction between insulin and leptin.

Metabolic control of type 1 diabetic patients followed at the University Children's Hospital in Berne: Have we reached the goal?

In type 1 diabetes (T1DM), a good metabolic control is important to reduce and/or postpone complications. Guidelines regarding how to achieve this goal are published by the American Diabetes Association (ADA) and the International Society of Paediatric and Adolescence Diabetes (ISPAD). The aims of this study were to determine the current level of metabolic control in T1DM patients on different treatment regimens, followed at the diabetes outpatient unit of the University Children's Hospital Bern, Switzerland, and to compare it with both the reported data from ten years ago (1998) and with the current guidelines of the ADA and ISPAD.

Retinal overexpression of angiopoietin-2 mimics diabetic retinopathy and enhances vascular damages in hyperglycemia

Our previous data suggested that angiopoietin-2 (Ang-2) is linked to pericyte loss, thereby playing an important role in diabetic retinopathy. In this study, we investigated the effect of retinal overexpression of human Ang-2 (mOpsinhAng2 mouse) on vascular morphology in non-diabetic and streptozotozin-induced diabetic animals. Pericyte (PC) coverage and acellular capillary (AC) formation were quantitated in retinal digest preparations after 3 and 6 months of diabetes duration. The degree of retinopathy in non-diabetic mOpsinhAng2 mice at 3 months (-21% PC, +49% AC) was comparable to age-matched diabetic wild type mice. Diabetic mOpsinhAng2 mice exhibited significantly worse vascular pathology than wild type counterparts at 6 months. Quantitative PCR revealed that human Ang-2 mRNA was highly overexpressed in retinas of transgenic mice. Our data demonstrate that overexpression of Ang-2 in the retina enhances vascular pathology, indicating that Ang-2 plays an essential role in diabetic vasoregression via destabilization of pericytes.

[Right-sided lower abdominal pain and diarrhea of a young diabetic woman]

We report the case of a 24-years old diabetic women hospitalised because of right-sided lower abdominal pain and diarrhea. She fulminantly developed shock before appendectomy could be performed and was transferred to intensive care unit. Hypotension remained and laparoscopy revealed primary peritonitis and toxic shock syndrome by Group A Streptococcus which was cultivated in blood and ascites. Therapy with penicilline and clindamycine resolved symptoms. During hospitalisation Clostridium difficile colitis occurred. This complication leaded to prolonged hospitalisation.

Safety and Efficacy of Ranibizumab in Diabetic Macular Edema (RESOLVE Study): A 12-month, randomized, controlled, double-masked, multicenter phase II study

The expression of vascular endothelial growth factor (VEGF) is elevated in diabetic macular edema (DME). Ranibizumab binds to and inhibits multiple VEGF variants. We investigated the safety and efficacy of ranibizumab in DME involving the foveal center.

Plaque characteristics of nonobstructive coronary lesions in diabetic patients: an intravascular ultrasound virtual histology analysis

Patients with diabetes mellitus are known to be at increased risk for acute cardiovascular events. We used intravascular ultrasound virtual histology (IVUS-VH) to examine whether nonobstructive coronary artery lesions of diabetic patients have distinct plaque composition and morphology compared with nondiabetic patients.

Delayed osteoblast differentiation and altered inflammatory response around implants placed in incisor sockets of type 2 diabetic rats

Objective: Central to the process of osseointegration is the recruitment of mesenchymal progenitor cells to the healing site, their proliferation and differentiation to bone synthesising osteoblasts. The process is under the control of pro-inflammatory cytokines and growth factors. The aim of this study was to monitor these key stages of osseointegration and the signalling milieu during bone healing around implants placed in healthy and diabetic bone. Methods: Implants were placed into the sockets of incisors extracted from the mandibles of normal Wistar and diabetic Goto-Kakizaki rats. Mandibles 1-12 weeks post-insertion of the implant were examined by histochemistry and immunocytochemistry to localise the presence of Stro-1- positive mesenchymal progenitor cells, proliferating cellular nuclear antigen proliferative cells, osteopontin and osteocalcin, macrophages, pro-inflammatory cytokines interleukin (IL)-1 , IL-6, tumour necrosis factor (TNF)- and tumour growth factor (TGF)- 1. Image analysis provided a semi-quantification of positively expressing cells. Results: Histological staining identified a delay in the formation of mineralised bone around implants placed in diabetic animals. Within the diabetic bone, the migration of Stro-1 mesenchymal cells in the healing tissue appeared to be unaffected. However, in the diabetic healing bone, the onset of cell proliferation and osteoblast differentiation were delayed and subsequently prolonged compared with normal bone. Similar patterns of change were observed in diabetic bone for the presence of IL-1 , TNF- , macrophages and TGF- 1. Conclusion: The observed alterations in the extracellular presence of pro-inflammatory cytokines, macrophages and growth factors within diabetic tissues that correlate to changes in the signalling milieu, may affect the proliferation and differentiation of mesenchymal progenitor cells in the osseointegration process. To cite this article: Colombo JS, Balani D, Sloan AJ, St Crean J, Okazaki J, Waddington RJ. Delayed osteoblast differentiation and altered inflammatory response around implants placed in incisor sockets of type 2 diabetic rats Clin. Oral Impl. Res22, 2011; 578-586 doi: 10.1111/j.1600-0501.2010.01992.x.

Predicting the pathogen of diabetic toe osteomyelitis by two consecutive ulcer cultures with bone contact

In this study, we investigate the accuracy of two consecutive ulcer cultures with bone contact compared to bone biopsy for the diagnosis of diabetic toe osteomyelitis. The same nurse and orthopaedic surgeon obtained all samples: sample A-1: bone contact swabbing through the ulcer; sample A-2: a second culture swabbing from the bone surface within 24 h; sample B: surgical bone biopsy in the operating theatre. The kappa statistic measure between samples A-1 and A-2 (bone contact swabs) indicated 82.35% agreement. The sensitivity, specificity, positive and negative predictive values of the two samples A compared to B were 96%, 79%, 92% and 88%, respectively, for the causative pathogen. These results were similar with prior antibiotic treatment, discordant bone surface swabs or with monomicrobial infections. As a conclusion, two consecutive diabetic toe cultures with bone contact accurately predict the pathogen of diabetic toe osteomyelitis in 90% of cases.

Chapter V: Diabetic foot

Ulcerated diabetic foot is a complex problem. Ischaemia, neuropathy and infection are the three pathological components that lead to diabetic foot complications, and they frequently occur together as an aetiologic triad. Neuropathy and ischaemia are the initiating factors, most often together as neuroischaemia, whereas infection is mostly a consequence. The role of peripheral arterial disease in diabetic foot has long been underestimated as typical ischaemic symptoms are less frequent in diabetics with ischaemia than in non-diabetics. Furthermore, the healing of a neuroischaemic ulcer is hampered by microvascular dysfunction. Therefore, the threshold for revascularising neuroischaemic ulcers should be lower than that for purely ischaemic ulcers. Previous guidelines have largely ignored these specific demands related to ulcerated neuroischaemic diabetic feet. Any diabetic foot ulcer should always be considered to have vascular impairment unless otherwise proven. Early referral, non-invasive vascular testing, imaging and intervention are crucial to improve diabetic foot ulcer healing and to prevent amputation. Timing is essential, as the window of opportunity to heal the ulcer and save the leg is easily missed. This chapter underlines the paucity of data on the best way to diagnose and treat these diabetic patients. Most of the studies dealing with neuroischaemic diabetic feet are not comparable in terms of patient populations, interventions or outcome. Therefore, there is an urgent need for a paradigm shift in diabetic foot care; that is, a new approach and classification of diabetics with vascular impairment in regard to clinical practice and research. A multidisciplinary approach needs to implemented systematically with a vascular surgeon as an integrated member. New strategies must be developed and implemented for diabetic foot patients with vascular impairment, to improve healing, to speed up healing rate and to avoid amputation, irrespective of the intervention technology chosen. Focused studies on the value of predictive tests, new treatment modalities as well as selective and targeted strategies are needed. As specific data on ulcerated neuroischaemic diabetic feet are scarce, recommendations are often of low grade.

Long-term clinical and angiographic outcomes of diabetic patients after revascularization with early generation drug-eluting stents

Early generation drug-eluting stents (DESs) reduce restenosis and repeat revascularization procedures. However, the long-term safety and efficacy of early generation DES according to diabetic status are poorly established.