Conventional deep pressure algometry is not suitable for clinical assessment of nociception in painless diabetic neuropathy.

Background: In diabetic persons with painless neuropathic foot ulceration, foot skin was found to be insensate to noxious pinprick stimulation (stimulation area less than 0.05 mm), while compression of deep subcutaneous foot tissues by Algometer II (stimulation area 1 cm) could evoke a deep dull aching. To elucidate this discrepancy, the Algometer II stimulation technique was critically reviewed by varying probe sizes and anatomical sites in the same study population 3 years later.

Nociception at the diabetic foot, an uncharted territory.

The diabetic foot is characterised by painless foot ulceration and/or arthropathy; it is a typical complication of painless diabetic neuropathy. Neuropathy depletes the foot skin of intraepidermal nerve fibre endings of the afferent A-delta and C-fibres, which are mostly nociceptors and excitable by noxious stimuli only. However, some of them are cold or warm receptors whose functions in diabetic neuropathy have frequently been reported.

Effect of painless diabetic neuropathy on pressure pain hypersensitivity (hyperalgesia) after acute foot trauma.

Introduction And Objective: Acute injury transiently lowers local mechanical pain thresholds at a limb. To elucidate the impact of painless (diabetic) neuropathy on this post-traumatic hyperalgesia, pressure pain perception thresholds after a skeletal foot trauma were studied in consecutive persons without and with neuropathy (i.e.

Insulin-induced localized lipoatrophy preceded by shingles (herpes zoster): a case report.

Introduction: Localized involutional lipoatrophy of subcutaneous adipose tissue may develop due to subcutaneous injection of pharmaceutical preparations. The pathogenesis of this adverse drug reaction is unknown. The progression of localized involutional lipoatrophy ceases and occasionally it resolves after withdrawing the inducing agent.

Is the Eichenholtz classification still valid for the diabetic Charcot foot?

In his 1966 monograph "Charcot joints", Sidney N. Eichenholtz (1909-2000) described "three well defined stages … in the course and development of a Charcot joint", based on plain X-rays of 68 patients. Since then, medical imaging has advanced very much: computed tomography and magnetic resonance imaging (MRI) scans exceed plain X-ray by far in detecting foot fractures and other injuries.

The acute diabetic Charcot foot managed on the basis of magnetic resonance imaging--a review of 71 cases.

Background: Acute Charcot foot (ACF) is a skeletal breakdown associated with inflammatory swelling of a foot in patients with pain insensitivity, such as diabetic neuropathy. In ACF stage 0, skeletal pathology (e.g.

Pressure pain perception in the diabetic Charcot foot: facts and hypotheses.

Background: Reduced traumatic and posttraumatic (nociceptive) pain is a key feature of diabetic neuropathy. Underlying condition is a gradual degeneration of endings of pain nerves (A-delta fibers and C-fibers), which operate as receivers of noxious stimuli (nociceptors). Hence, the absence of A-delta fiber mediated sharp pain ("first" pain), and of C-fiber mediated dull pain ("second" pain).

The diagnostic value of measuring pressure pain perception in patients with diabetes mellitus.

Question Under Study: Repetitive skin trauma and reduced pressure pain sensation are necessary components of plantar ulcer risk in patients with diabetic neuropathy. The diagnostic value of measuring pressure nociception to detect ulcer risk is, however, unknown. Instead, measuring the vibration perception threshold (VPT) by 64 Hz graduated Rydel-Seiffer tuning fork has become standard clinical practice to screen for neuropathy and ulcer proneness.

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

Introduction: Circumscript, progressing lipoatrophy at the insulin injection sites is an unexplained, however rare condition in diabetes mellitus.

Case Presentation: 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.

Differences in bioactivity between human insulin and insulin analogues approved for therapeutic use- compilation of reports from the past 20 years.

In order to provide comprehensive information on the differences in bioactivity between human insulin and insulin analogues, published in vitro comparisons of human insulin and the rapid acting analogues insulin lispro (Humalog®), insulin aspart ( NovoRapid®), insulin glulisine (Apidra®), and the slow acting analogues insulin glargine (Lantus®), and insulin detemir (Levemir®) were gathered from the past 20 years (except for receptor binding studies). A total of 50 reports were retrieved, with great heterogeneity among study methodology. However, various differences in bioactivity compared to human insulin were obvious (e.

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.

Sudeck's disease stage 1, or diabetic Charcot's foot stage 0? Case report and assessment of the diagnostic value of MRI.

Background: The diagnosis of Sudeck's syndrome stage 1 (nowadays termed complex regional pain syndrome I, abbreviated CRPS I) is based on clinical features, namely swelling and pain in a limb. Plain X-ray may be normal. In the absence of pain sensitivity, e.

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

Background: Imaging studies of bones in patients with sensory deficits are scarce.

Aim: To investigate bone MR images of the lower limb in diabetic patients with severe sensory polyneuropathy, and in control subjects without sensory deficits.

Methods: 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.

Treatment with insulin glargine (Lantus) increases the proliferative potency of the serum of patients with type-1 diabetes: a pilot study on MCF-7 breast cancer cells.

Context And Objective: Insulin glargine (Lantus) stimulates growth of MCF-7 cells stronger than human insulin. We investigated if serum from diabetic patients treated with glargine versus human insulin may display a similar effect.

Methods: Pairs of serum samples from 31 C-peptide negative type-1 diabetic patients were investigated.

Downregulation of serum IGF-1 for treatment of early worsening of diabetic retinopathy: a long-term follow-up of two cases.

In 2003, we reported on 2 cases of nonproliferative and proliferative diabetic retinopathy, subsequent to HbA1c reduction by intensive insulin therapy (so-called early worsening of diabetic retinopathy). This acute condition could partly be reversed by discontinuation of intensive insulin therapy, whereby glycemia increased and serum IGF-1 concentration decreased [Ophthalmologica 2003;217:373-377]. On review 7 years later, both type-2 diabetic patients were on insulin therapy but had failed to achieve good glycemic control.

Insulin-responsiveness of tumor growth.

In October 2008, the 2nd International Insulin & Cancer Workshop convened roughly 30 researchers from eight countries in Düsseldorf/Germany. At this meeting, which was industry-independent like the preceding one in 2007, the following issues were discussed a) association between certain cancers and endogenous insulin production in humans, b) growth-promoting effects of insulin in animal experiments, c) mitogenic and anti-apoptotic activity of pharmaceutic insulin and insulin analogues in in vitro experiments, d) potential mechanisms of insulin action on cell growth, mediated by IGF-1 receptor and insulin receptor signaling, and e) IGF-1 receptor targeting for inhibition of tumor growth. It was concluded that further research is necessary to elucidate the clinical effects of these observations, and their potential for human neoplastic disease and treatment.

Insulin, insulin analogues and diabetic retinopathy.

Insulin is absolutely vital for living beings. It is not only involved in metabolism, but also in the regulation of growth factors, e.g.

Nonoperative treatment of neuro-osteoarthropathy of the foot: do we need new criteria?

The worst manifestation of neuro-osteoarthropathy of the pain-insensitive foot is the Charcot foot with its devastating osteoarticular destructions and irreversible deformities. New diagnostic tools such as MRI have revealed that mechanical injury and overuse is the origin of the condition. Traditionally, only feet with bone and joint damage apparent on plain radiographs (fracture and dislocation injuries) have undergone nonoperative treatment with off-loading and immobilization; however, treating painless, seemingly asymptomatic nonfracture injuries (bone bruise or bone marrow edema) with off-loading and immobilization has proven highly effective in preventing the Charcot foot.

Bone histomorphology may be unremarkable in diabetes mellitus.

Background And Purpose: Histomorphological studies on bone in human diabetes mellitus are scarce. The aim of this study was to observe the histomorphological appearance of bone in amputation specimens from feet of patients with diabetes mellitus.

Material And Methods: Routine histopathology reports on 45 amputation specimens were evaluated, provided the osteotomy was located in unaffected bone tissue.