Characteristics and morphology of lipohypertrophic lesions in adults with type 1 diabetes with ultrasound screening: an exploratory observational study.

INTRODUCTION: Lipohypertrophy is a common complication of exposure to insulin therapy. Despite the prevalence of lipohypertrophy and its potentially hazardous effects on glucose regulation, it remains a relatively understudied problem in diabetes. The objective of this study was to characterize lipohypertrophic tissue using ultrasound in adults with type 1 diabetes. RESEARCH DESIGN AND METHODS: An observational study of 74 people with type 1 diabetes from a diabetes center in South East London. Participants' insulin exposed areas were scanned with ultrasound, with a high-frequency linear probe (6-13 MHz). The observed tissue changes were described, measured and graded according to nodule size and thickness of the dermal layer. RESULTS: Participants mean age and diabetes duration were 40.6 (±14.2) and 18.3 (±10.9) years, respectively, and 60% (n=44) were male. A total of 740 lipohypertrophic nodules were observed, ranging from 1.8 mm to 40 mm in width. The mean (SD/range) number of nodules per participants was 10.4 (±6.2/1-29). Delineation between the dermal layers was disrupted in all current injection sites. In 52 participants (70%), there was a 30% increase in dermal thickness compared with local none injected tissue, and in 36 participants (48%) the increase was 50%. The level of thickness was >3 mm in the abdominal areas of 22 (40%) of these participants and in thighs of eight participants (17.8%). Hypoechogenic areas suggestive of necrotic tissue were observed within the lipohypertrophic nodules of 22 (30%) participants. Needle length and nodule depth were correlated (r=0.69, p<0.001). A conceptual model of the insulin exposed tissue changes observed was constructed. CONCLUSIONS: The study confirms that insulin-exposed tissue changes are heterogenous and has provided conceptual and grading frameworks for classifying these changes. Further studies are required to establish the clinical implications of these classifications, in relation to glucose regulation and other clinical parameters.

A systematic review of community Leg Clubs for patients with chronic leg ulcers.

AIM: Appraise the evidence on the outcomes of Leg Clubs on ulcer healing, psychosocial outcomes, patient safety, cost and experiences of Leg Club members. BACKGROUND: The Leg Club is a community-based social model of care in 30 UK locations and nine overseas for treating patients with chronic leg wounds. However, its cumulative effectiveness has not been reviewed to-date. METHODS: Systematic review of primary research relating to the impact and quality of care of Leg Clubs treating patients with leg ulcers. Six electronic databases were systematically searched using the MeSH term 'leg ulcer', including other representative terms, in combination with 'Leg Club'. The quality of individual studies was assessed using appraisal tools. The confidence in the quantitative evidence was evaluated using Grading of Recommendations Assessment, Development and Evaluation (GRADE); and the Confidence in the Evidence from Reviews of Qualitative Research (CERQual) assessed the quality of qualitative findings. FINDINGS: A total of 17 relevant publications were identified. Out of the 17 articles, four publications represent findings from randomised controlled trial (RCT). Thus, evidence from 14 independent studies involving at least 532 participants were included in the synthesis of this review. The quality of the evidence varied across the different outcomes and were mostly low or of very low quality. Findings from one underpowered RCT from Australia reporting on clinical, patient-reported outcomes and economic outcomes were evaluated as moderate quality. Studies indicate that the Leg Club model has a positive impact on ulcer healing and recurrence, mood, sleep, quality of life and pain. Moreover, only three studies assessed wound infections and reported no infections had occurred during treatment at the Leg Clubs. Economic evaluations find Leg Clubs to be probably more cost-effective than usual care. Both patients and nurses projected positive views about the Leg Clubs, with particular emphasis on improved social interactions and delivery of patient-centred care.

A Systematic Review of Ultrasound-Detected Lipohypertrophy in Insulin-Exposed People with Diabetes.

INTRODUCTION: Lipohypertrophy (LH) is a common complication occurring in diabetes individuals. The most common methods used include palpation, visual examination and/or ultrasound (US). To date, there is limited information on the detection sensitivity among the different techniques used to identify LH. This systematic review aimed to identify studies that examined insulin-related LH using US detection to identify the prevalence, characteristics and morphology of LH, and to compare US and clinical palpation methods for detecting LH. METHODS: Three electronic databases were systematically searched for studies detecting LH using US in insulin users. Articles were screened for eligibility and included studies were appraised using quality assessment tools. The quality of the evidence was evaluated using Grading of Recommendations Assessment, Development and Evaluation, and the extracted data was synthesised narratively. RESULTS: Sixteen articles were included in the review providing data on 1722 patients. The prevalence of LH prevalence varied from 14.5% to 88% (median 56.6%). Identified risk factors for the development of included insulin injection behaviour such as a lack of injection site rotation and social factors such as low education level. Four studies compared LH detection by US to palpation, providing inconsistent results. One study showed that palpation detected 64% more LH, whilst two studies demonstrated that US identified 50% more sites and extended areas of LH (additional ~ 5 cm2). Another study provided comparable estimates between palpation and US in clinicians trained to detect LH (97%). CONCLUSION: The evidence highlights a lack of congruence in results pertaining to the detection sensitivity of US and palpation for LH sites. More research with robust study design is needed to verify whether clinically palpation is sufficient to detect LH, or whether US would increase the precision of LH assessment to help address this common clinically significant problem.

A qualitative approach exploring the experiences of smoking and quitting attempts in type 1 diabetes.

AIMS AND OBJECTIVES: To explore the experiences of smoking and quitting attempts in people with type 1 diabetes, including their perceptions of existing services for smoking cessation. BACKGROUND: In the UK, approximately a fifth of the population with type 1 diabetes smoke and despite the adverse effects of smoking, these individuals continue with their smoking habits. There is limited information on the barriers and facilitators to quitting smoking in people with type 1 diabetes. METHODS: This study adopted a qualitative study design using semi-structured individual interviews guided by PRIME theory. Participants (n = 12) were purposively sampled and recruited from two diabetes outpatient clinics in London (UK). Audio-recorded interviews were transcribed verbatim and analysed using the Framework method. RESULTS: Most smokers with type 1 diabetes reported lack of motivation to stop smoking due to the addictive nature of cigarettes. Further barriers to quitting included self-image and habits associated with smoking, such as social activities. Generally, most reported limited awareness about the risks associated with smoking and diabetes. Moreover, the perceived negative attitude towards nicotine replacement therapy and pharmacotherapy impeded their willingness to alter their smoking habits. Nonetheless, these patients suggested that informative guidance from medical professionals and strategies to tackle cravings related to nicotine as helpful approaches to improve quitting attempts. CONCLUSION: Internal and external factors influence quitting attempts among smokers with type 1 diabetes, with particular emphasis on self-image and societal norms. It is evident that existing strategies for smoking cessation recommended by the National Institute for Health and Care Excellence have either not been implemented or not well received by people with type 1 diabetes. RELEVANCE TO CLINICAL PRACTICE: Strategies and resources, such as staff training, to increase delivery of smoking cessation support to patients with diabetes are needed.

Harmane: an atypical neurotransmitter?

Harmane is an active component of clonidine displacing substance and a candidate endogenous ligand for imidazoline binding sites. The neurochemistry of tritiated harmane was investigated in the present study examining its uptake and release properties in the rat brain central nervous system (CNS) in vitro. At physiological temperature, [(3)H]harmane was shown to be taken up in rat brain cortex. Further investigations demonstrated that treatment with monoamine uptake blockers (citalopram, nomifensine and nisoxetine) did not alter [(3)H]harmane uptake implicating that the route of [(3)H]harmane transport was distinct from the monoamine uptake systems. Furthermore, imidazoline ligands (rilmenidine, efaroxan, 2-BFI and idazoxan) showed no prominent effect on [(3)H]harmane uptake suggesting the lack of involvement of imidazoline binding sites. Subsequent analyses showed that disruption of the Na(+) gradient using ouabain or choline chloride did not block [(3)H]harmane uptake suggesting a Na(+)-independent transport mechanism. Moreover, higher temperatures (50°C) failed to impede [(3)H]harmane uptake implying a non-physiological transporter. The failure of potassium to evoke the release of preloaded [(3)H]harmane from rat brain cortex indicates that the properties of this putative endogenous ligand for imidazoline binding sites do not resemble that of a conventional neurotransmitter.

The modulatory action of harmane on serotonergic neurotransmission in rat brain.

The naturally occurring ß-carboline, harmane, has been implicated in various physiological and psychological conditions. Some of these effects are attributed to its interaction with monoaminergic systems. Previous literature indicates that certain ß-carbolines including harmane modulate central monoamine levels partly through monoamine oxidase (MAO) inhibition. However, this is not always the case and thus additional mechanisms may be involved. This study set to assess the potential modulatory role of harmane on the basal or K(+) stimulated release of preloaded radiolabelled noradrenaline (NA), dopamine (DA) and serotonin (5-HT) in rat brain cortex in vitro in the presence of the MAO inhibitor pargyline. Harmane displayed an overt elevation in K(+) -evoked [(3)H]5-HT release; whilst little and no effect was reported with [(3)H]DA and [(3)H]NA respectively. The effect of harmane on [(3)H]5-HT efflux was partially compensated in K(+)-free medium. Further analyses demonstrated that removal of Ca(2+) ions and addition of 1.2mM EGTA did not alter the action of harmane on [(3)H]5-HT release from rat brain cortex. The precise mechanism of action however remains unclear but is unlikely to reflect an involvement of MAO inhibition. The current finding aids our understanding on the modulatory action of harmane on monoamine levels and could potentially be of therapeutic use in psychiatric conditions such as depression and anxiety.

The effect of 1-(4,5-dihydro-1H-imidazol-2-yl) isoquinoline on monoamine release and turnover in the rat frontal cortex.

Imidazoline-(2) binding sites (I(2)-BS) are widely distributed in rat brain and our studies have shown that drugs selective for these sites regulate central extrasynaptic monoamine concentrations. Radioligand binding studies have recently shown that BU98008 (1-[4,5-dihydro-1H-imidazol-2-yl] isoquinoline) displays high affinity at I(2)-binding sites. The aim of this study was set to assess the pharmacological actions of BU98008 in a functional in vivo model using the technique of in vivo brain microdialysis. Systemic injection of 20 mg/kg BU98008 produced an 85% rise in extracellular noradrenaline levels compared with basal values in the rat frontal cortex. Further experiments demonstrated that peripheral administration of 10 and 20 mg/kg BU98008 elicited a transient 25% elevation in dopamine overflow compared with basal values and simultaneously produced an 18% decrease in extracellular DOPAC (3-4-dihydroxyphenylacetic acid) levels compared to basal values. In addition, BU98008 did not appear to affect serotonergic neurotransmission in the frontal cortex. In conclusion, the present study demonstrates that BU98008 shares some functional similarities with known selective I(2)-BS ligands.