Meeting Report: 3rd International Workshop on Insulin & Cancer Heidelberg, Germany, October 30-31, 2010

The 3rd International Workshop on Insulin & Cancer was held on October 30-31, 2010 at the German Cancer Research Centre in Heidelberg/Germany. The topics followed-up the discussions of the previous workshops: possible differences in mitogenicity between natural insulin and genetically engineered insulin derivatives (insulin analogues), as shown by laboratory studies and epidemiologic studies alike; molecular studies on the links between metabolic and mitogenic effects of insulin, and of hyperinsulinaemia in particular; epidemiologic evidence of interferences between insulin and other hormones, particularly sex hormones, and obesity-associated cancer; the involvement of inflammatory cytokines produced by fat tissue in obesity-associated cancer; aspects of drug-design (binding drugs to albumin) and, last but not least, detection and investigation of circulating cancer cells

Routine MRI findings of the asymptomatic foot in diabetic patients with unilateral Charcot foot

<p>Abstract</p> <p>Background</p> <p>Imaging studies of bones in patients with sensory deficits are scarce.</p> <p>Aim</p> <p>To investigate bone MR images of the lower limb in diabetic patients with severe sensory polyneuropathy, and in control subjects without sensory deficits.</p> <p>Methods</p> <p>Routine T1 weighted and T2-fat-suppressed-STIR-sequences without contrast media were performed of the asymptomatic foot in 10 diabetic patients with polyneuropathy and unilateral inactive Charcot foot, and in 10 matched and 10 younger, non-obese unmatched control subjects. Simultaneously, a Gadolinium containing phantom was also assessed for reference. T1 weighted signal intensity (SI) was recorded at representative regions of interest at the peritendineal soft tissue, the tibia, the calcaneus, and at the phantom. Any abnormal skeletal morphology was also recorded.</p> <p>Results</p> <p>Mean SI at the soft tissue, the calcaneus, and the tibia, respectively, was 105%, 105% and 84% of that at the phantom in the matched and unmatched control subjects, compared to 102% (soft tissue), 112% (calcaneus) and 64% (tibia) in the patients; differences of tibia vs. calcaneus or soft tissue were highly significant (p < 0.005). SI at the tibia was lower in the patients than in control subjects (p < 0.05). Occult traumatic skeletal lesions were found in 8 of the 10 asymptomatic diabetic feet (none in the control feet).</p> <p>Conclusion</p> <p>MR imaging did not reveal grossly abnormal bone marrow signalling in the limbs with severe sensory polyneuropathy, but occult sequelae of previous traumatic injuries.</p

Management and efficacy of intensified insulin therapy starting in outpatients

Diabetic patients under multiple injection insulin therapy (i.e., intensified insulin therapy, IIT) usually start this treatment during hospitalization. We report here on the logistics, efficacy, and safety of IIT, started in outpatients. Over 8 months, 52 type I and type II diabetics were followed up whose insulin regimens consecutively had been changed from conventional therapy to IIT. Two different IIT strategies were compared: free mixtures of regular and intermediate (12 hrs)-acting insulin versus the basal and prandial insulin treatment with preprandial injections of regular insulin, and ultralente (24 hrs-acting) or intermediate insulin for the basal demand. After 8 months HbA1 levels had decreased from 10.6%±2.4% to 8.0%±1.3% (means±SD). There was no difference between the two regimens with respect to metabolic control; but type II patients maintained the lowered HbA1 levels better than type I patients. Only two patients were hospitalized during the follow-up time because of severe hypoglycemia. An increase of body weight due to the diet liberalization during IIT became a problem in one-third of the patients. Our results suggest that outpatient initiation of IIT is safe and efficacious with respect to near-normoglycemic control. Weight control may become a problem in IIT patients

Relapsing insulin-induced lipoatrophy, cured by prolonged low-dose oral prednisone: a case report

<p>Abstract</p> <p>Introduction</p> <p>Circumscript, progressing lipoatrophy at the insulin injection sites is an unexplained, however rare condition in diabetes mellitus.</p> <p>Case presentation</p> <p>We report a case of severe localised lipoatrophy developing during insulin pump-treatment (continuous subcutaneous insulin infusion) with the insulin analogue lispro (Humalog^®) in a woman with type-1 diabetes mellitus. After 11 months of progressing lipoatrophy at two spots on the abdomen, low-dose prednisone (5-10 mg) p.o. was given at breakfast for 8 months, whereby the atrophic lesions centripetally re-filled with subcutaneous fat tissue (confirmed by MRI) despite ongoing use of insulin lispro. However, 4 weeks after cessation of prednisone, lipoatrophy relapsed, but resolved after another 2 months of low-dose prednisone. No further relapse was noted during 12 months of follow-up on insulin-pump therapy with Humalog^®.</p> <p>Conclusion</p> <p>Consistent with an assumed inflammatory nature of the condition, low-dose oral prednisone appeared to have cured the lipoatrophic reaction in our patient. Our observation suggests a temporary intolerance of the subcutaneous fat tissue to insulin lispro (Humalog^®), triggered by an unknown endogenous mechanism.</p

5 year retrospective follow-up of new cases of Charcot neuroarthropathy - A single centre experience

Background: Few data describe the natural history of Charcot neuroarthropathy treated with a total contact plaster cast (TCC). Methods: A 5 year retrospective analysis of 50 patients presenting with an acute CN, Assessing time to clinical resolution into appropriate footwear and assessing if initial immobilisation device influenced resolution time. Results: During the study period 42 patients (84%) of patients went into remission, 2 died during their treatment, 4 had major amputations, in 2 patients treatment was ongoing. 36 patients were treated with combination offloading devices, 6 were treated with one modality only. Median time to resolution for patients initially treated with a TCC was not significantly shorter than for those treated with a removable below knee boot. 34.9% required re-casting due to clinical deterioration in the removable device. Conclusions: More precise measures of resolution of CN are needed to assess the impact of initial treatment modality on time to resolution

Barefoot vs common footwear:A systematic review of the kinematic, kinetic and muscle activity differences during walking

Habitual footwear use has been reported to influence foot structure with an acute exposure being shown to alter foot position and mechanics. The foot is highly specialised thus these changes in structure/position could influence functionality. This review aims to investigate the effect of footwear on gait, specifically focussing on studies that have assessed kinematics, kinetics and muscle activity between walking barefoot and in common footwear. In line with PRISMA and published guidelines, a literature search was completed across six databases comprising Medline, EMBASE, Scopus, AMED, Cochrane Library and Web of Science. Fifteen of 466 articles met the predetermined inclusion criteria and were included in the review. All articles were assessed for methodological quality using a modified assessment tool based on the STROBE statement for reporting observational studies and the CASP appraisal tool. Walking barefoot enables increased forefoot spreading under load and habitual barefoot walkers have anatomically wider feet. Spatial-temporal differences including, reduced step/stride length and increased cadence, are observed when barefoot. Flatter foot placement, increased knee flexion and a reduced peak vertical ground reaction force at initial contact are also reported. Habitual barefoot walkers exhibit lower peak plantar pressures and pressure impulses, whereas peak plantar pressures are increased in the habitually shod wearer walking barefoot. Footwear particularly affects the kinematics and kinetics of gait acutely and chronically. Little research has been completed in older age populations (50+ years) and thus further research is required to better understand the effect of footwear on walking across the lifespan