Impairment and recovery of elementary cognitive function induced by hypoglycemia in type-1 diabetic patients and healthy controls

Although neuroendocrine changes after induction of hypoglycemia, in patients with diabetes and healthy persons, are thoroughly investigated, cognitive adaptation processes are still insufficiently understood. Changes in cognitive functions are mainly investigated by psychometric tests, which represent a summation of different cognitive processes. We aimed at dissecting cognitive adaptation into single components, i.e. stimulus selection, response choice, and reaction speed during a hyperinsulinemic hypoglycemic clamp in patients with type-1 diabetes and matched healthy controls. Using novel neurophysiological analyses, the event-related potentials of early stimulus selection (selection negativity) and response selection (lateralized readiness potential) were studied, in addition to reaction time (RT). A total of 12 diabetic patients and 12 normal volunteers were studied while receiving a hyperinsulinemic hypoglycemic clamp. RTs and the event-related potentials related to stimulus selection and response selection were significantly delayed during hypoglycemia in both groups, whereas early evoked potentials (P100) were unaltered. This suggests that hypoglycemia delays stimulus selection, with the consequence that also central and motor processing are delayed. In addition, patients with diabetes showed an earlier negative shift over the frontal cortex, which, when compared with the controls, reveals better adaptation to hypoglycemia in frontal cortical brain regions. After restoration of euglycemia stimulus selection, response selection and RT returned to baseline level in the type-1 group. In the control group, however, response selection and RTs were still delayed. This suggests that type-1 patients, possibly because of the past occurrence of hypoglycemic events, might be able to better cope with the hypoglycemic state than healthy volunteers who lack such a history. In summary, our data demonstrate, for the first time, that cognitive adaptation processes to an experimental hypoglycemic episode can clearly be dissected into their single components.     

Association between “diabetic thick skin syndrome” and neurological disorders in diabetes mellitus

Skin thickness on the extremities of patients with diabetes mellitus has been described controversially. Using high resolution ultrasonography, we were able to show a significant increase in skin thickness at the forearm (P<0.05), thigh (P<0.001) and lower limb (P<0.05) of diabetic patients, most prominent at the thigh. No difference in skin thickness was found at the dorsum of the foot. In addition, skin thickness was not related to the duration of diabetes, age or HbA₁. A close association was found between diabetic neuropathy and increasing skin thickness. Diabetic patients with neurological disorders had a significant increase in skin thickness versus diabetic patients without neuropathy. The present findings suggest that diabetic neuropathy and abnormalities of connective tissue have a common etiological link in their development or that both are time-dependent processes. Whether changes in capillary blood flow, increase of nonenzymatic glycosylation, polyol accumulation or other metabolic disorders are responsible for these findings remains still to be established.     

Antibiotic therapy for diabetic foot infections: comparison of cephalosporines with chinolones

Diabetic foot complications are the most common cause of non-traumatic lower extremity amputations and uncontrolled infections represent a major risk factor. This open prospective, multicenter trial compared the efficacy of two antibiotic regimens for treatment of foot infections Wagner stage II or III in diabetic adults. Three hundred diabetic patients with severe, limb-threatening foot infection were consecutively enrolled in a prospective, observational, matched pairs controlled study to test two different antibiotic regimes (ceftriaxone vs chinolones) in addition to standard treatment of foot infection. After matching, 90 patients--each receiving ceftriaxone or chinolones--were analyzed. Our study demonstrated that treatment with a third generation cephalosporine is as effective as a treatment with chinolones. Response (reaching Wagner I or 0) was achieved in 58.0% in the ceftriaxone group and in 51.1% in the chinolone group (NS.). Fourteen days after initiation of treatment, the number of patients with microbiological isolates decreased in both groups (52 to 5 in the ceftriaxone group and 60 to 12 in the chinolone group). At hospital discharge, 66.0% of ceftriaxone and 64.4 of chinolone-treated diabetic ulcers were cured or improved. In summary, both substances proved to be effective in the primary antibiotic treatment of the diabetic foot; an early broad spectrum antibiotic treatment, that covers both gram-positive and gram negative bacteria as well as anerobes is undisputedly an imperative therapeutic intervention for the treatment of diabetic foot infection.     

Mikrobiologische Aspekte und rationelle antibiotische Therapie des diabetischen Fu?syndroms

Zusammenfassung. q Immunologische und mikrobiologische Aspekte des diabetischen Fußulkus: Diabetische Patienten sind einem erhöhten Risiko für schwere Weichteil- und Knocheninfektionen ausgesetzt. Einerseits spielt hier die veränderte patientenabhängige Immunkompetenz eine Rolle, die von einer eingeschränkten spezifischen und unspezifischen zellulären Immunität herrührt. Andererseits zeigen die Epidemiologie des Erregerspektrums und die erregerspezifische Pathogenität, dass insbesondere Staphylokokken für dieses Krankheitsbild prädestiniert zu sein scheinen: Staphylococcus aureus und koagulasenegative Staphylokokken besitzen Eigenschaften, die ihnen die Adhärenz auf Wundoberflächen ermöglichen. Hierzu zählen zunächst unspezifische Mechanismen wie Ionenwechselwirkungen und Hydrophobizität zwischen bakterieller und Wirtszelloberfläche wie auch spezifische Interaktionen zwischen bakteriellen Adhäsinen und zellulären Rezeptoren. Darüber hinaus sezernieren Staphylokokken Polysaccharide, die gemeinsam mit den phänotypischen Veränderungen der Infektionserreger und der Ausbildung von Mikrokolonien zur Bildung eines Biofilms führen können. Dieses strukturierte Konglomerat aus Bakterien, Polysacchariden und Wirtsproteinen zeigt eine ausgesprochene Resistenz gegenüber immunologischen Effektoren und antimikrobiellen Substanzen und neigt deshalb zur chronischen Persistenz. q Aspekte der antibiotischen Therapie: Vor Beginn einer Therapie ist der Schweregrad der Infektion abzuschätzen, da hiervon sowohl die Auswahl und Darreichungsform des Antibiotikums als auch die Dauer der Therapie abhängen. Die initiale Therapie bei schweren und länger bestehenden Infektionen sollte mit einem Breitspektrumantibiotikum in parenteraler Applikation zum Erreichen schneller Wirkspiegel durchgeführt werden. Bei bestehender Osteomyelitis muss die Therapie aufgrund der hohen Rückfallquote häufig über > 4 Wochen durchgeführt werden, bei oberflächlichen Infektionen der Weichteile reichen im Regelfall 1-2 Wochen aus. q Schlussfolgerung und Ausblick: Aufgrund der erheblichen Fortschritte auf dem Gebiet der Diagnostik und Therapie des diabetischen Fußsyndroms besteht allgemeiner Konsens, dass mit einer optimalen Wundversorgung, einer metabolischen Kontrolle und einer frühen aggressiven chirurgischen und antibiotischen Intervention Infektionen kontrolliert werden können. Die Problematik der Biofilmbildung bei chronischen Infektionen ist bislang noch wenig in das Bewusstsein des Therapeuten gedrungen, erklärt aber im Einzelfall die geringe Effektivität einer antimikrobiellen Therapie. Abseits der Anwendung der klassischen Antibiotika gibt es hier erfolgversprechende Ansätze einer enzymatischen Behandlung bzw. einer Inhibition der bakteriellen "Kommunikation" ("quorum sensing"), die für eine effizientere Therapie zukünftig von Bedeutung sein können. Abstract. q Immunological and Microbiological Aspects of Diabetic Foot Infections: Diabetic patients are at increased risk of severe skin and bone infections. Immunological disturbances are reasonable and due to altered specific and unspecific cellular immune responses. Analysis of epidemiology and microbial pathogenicity shows that staphylococci seem to be predestined to induce such infections. Staphylococcus aureus and coagulase-negative staphylococci are able to adhere to the wound ground by a sequela of mechanisms. Initial bacterial adherence is due to hydrophobicity, ion exchanges, and specific binding of bacterial adhesion molecules to cellular receptors. Moreover, staphylococci secrete polysaccharides which form a biofilm together with multilayer cell clusters. The highly structured communities within a biofilm are resistant to distinct immunoeffectors and have a decreased susceptibiliy to antibiotics in vivo. q Aspects of Antibiotic Therapy: Assessing the severity of an infection is essential to selecting an antibiotic regimen, the mode of drug administration, and the duration of therapy. Regimens for severe and chronic infections are broader spectrum and often intravenously to obtain high drug concentrations immediately. Infections of the bone often require an antibiotic therapy for > 4 weeks, while a 1- to 2-week therapy for mild to moderate infections has been found to be effective. q Conclusions: Because of the tremendous progress in diagnostics and therapy of diabetic foot infections, infectious complications can be successfully treated by appropriate wound care, metabolic control, and early surgical and antibiotic intervention. Bacterial biofilms involved into chronic infections are new aspects currently not visualized by clinical therapy. Besides the classic antimicrobial therapy, new concepts of an enzymatic therapy or the inhibition of bacterial "communication" (quorum sensing) are in progress and the hope for the future.     

Autologous human keratinocytes cultured on membranes composed of benzyl ester of hyaluronic acid for grafting in nonhealing diabetic foot lesions: a pilot study

Diabetic foot complications are the most common cause of nontraumatic lower extremity amputations in the industrialised world. Unsatisfactory healing requires advanced therapeutic strategies, such as the use of skin grafts, which may represent a helpful option for wound coverage. Alternatively, a method using autologous keratinocytes grown to thin sheet grafts is available. The purpose of this pilot study was to investigate the application of autologous human keratinocytes cultured on membranes composed of benzyl ester of hyaluronic acid (Laserskin autograft) to diabetic foot ulcers. We studied 14 patients with type 2 diabetes mellitus and a nonhealing diabetic foot lesion, defined as existing longer than 6 months or with no wound healing apparent for 12 weeks. Between 7 and 64 days after the transplantation (depending on the size of the ulceration), 11/14 of the lesions were completely healed. The transplantation of autologous keratinocytes may allow faster closure of diabetic foot lesions and subsequently reduce length of hospitalization. This method can easily be planned with regard to logistics and time, and furthermore, this therapy option can be carried out by the diabetologist.     

Hypoglyk?mie trotz Hyperglyk?mie Ist eine zerebrale Minderversorgung mit Glukose auch bei erh?htem Blutzuckerspiegel m?glich?

Hypoglykämien stellen den häufigsten endokrinologischen Notfall in der prähospitalen Patientenversorgung dar. Da die Erkrankten bei Ankunft des Notarztes meist bewusstseinsgestört sind, ist eine Diagnosesicherung häufig allein durch Bestimmung des Blutglukosespiegels möglich. Selbst bei normo- bzw. hyperglykämischen Messergebnissen kann eine stattgehabte Hypoglykämie als Ursache eines akuten zerebralen Defizits nicht mit Sicherheit ausgeschlossen werden und muss, besonders bei insulinpflichtigen Diabetes-mellitus-Patienten, differenzialdiagnostisch erwogen werden. Wir berichten über die notärztliche Diagnosestellung und Therapie einer hypoglykämischen Episode einer Patientin mit prolongierter Neuroglykopenie bei gleichzeitig vorliegender zerebrovaskulärer Demenz und Morbus Alzheimer.