Possibility of adiponectin use to improve islet transplantation outcomes

Although islet transplantation (ITx) is a promising therapy for severe diabetes mellitus, further advancements are necessary. Adiponectin, an adipokine that regulates lipid and glucose metabolism, exerts favorable effects on islets, such as reinforcement of the insulin-releasing function. This study evaluated the possibility of adiponectin use to improve ITx outcomes. We treated mouse islets with 10 µg/mL recombinant mouse adiponectin by overnight culture and then assessed the insulin-releasing, angiogenic, and adhesion functions of the islets. Furthermore, 80 syngeneic islet equivalents with or without adiponectin treatment were transplanted into the renal subcapsular space of diabetic mice. In in vitro assessment, released insulin at high glucose stimulation, insulin content, and expressions of vascular endothelial growth factor and integrin β1 were improved in adiponectin-treated islets. Furthermore, adiponectin treatment improved the therapeutic effect of ITx on blood glucose levels and promoted angiogenesis of the transplanted islets. However, the therapeutic effect was not pronounced in glucose tolerance test results. In conclusion, adiponectin treatment had preferable effects in the insulin-releasing, angiogenic, and adhesion functions of islets and contributed to the improvement of ITx. The future use of adiponectin treatment in clinical settings to improve ITx outcomes should be investigated.

Empiric Treatment of Foot Infection in Patients with Severe Diabetes

Background: Despite being treated with antibiotics of broad spectrum recommended by International Consensus, severe diabetic patients with lower limb infection do not present a positive clinical evolution during empirical treatment. This study’s bacterial profile was analysed and compared with other worldwide hospital centers. Objective: To confirm the need of an individualized empirical treatment for severe diabetic patients with foot infection. Methods: Retrospective analysis of cultures and antibiograms of severe diabetic patients admitted by foot infection. Results: The results were consistent with the socioeconomic realities of developing countries. Gram-negative bacteria (52,11%) were present in most bone cultures. Results presented a high incidence of Enterococcus faecalis in both gram-positive (21,2%) and polymicrobial (34,7%) samples. Bacterial resistance with the use of ordinary antibiotics in the statistical analysis was high. Conclusion: The community infections should undergo broad spectrum empirical therapy combining amikacin (80,43%) or meropenem (72,00%) with gram-negative and vancomycin (100%) or teicoplanin (90,00%) or linezolid (74,19%) with gram-positive.

Therapeutic effects of acylated ghrelin-specific receptor GHS-R1a antagonist in islet transplantation

Islet transplantation is a type of cellular replacement therapy for severe diabetes that is limited by compromising effect on engrafted islets. Trials aiming to improve the function of transplanted islets have also been challenging. This study attempted to elucidate whether regulation of growth hormone secretagogue receptor-1a (GHS-R1a), one of the ghrelin receptors, improve the therapeutic effects of islet transplantation using [D-Lys3]-GHRP-6 (DLS), a specific GHS-R1a antagonist. The therapeutic effects of DLS were assessed in terms of the expression/production of endocrine genes/proteins, insulin-releasing function under glucose stimulation of mouse islets, and outcomes of syngeneic murine islet transplantation with systemic DLS administration. DLS treatment promoted insulin production and suppressed somatostatin production, suggesting that cancelation of the binding between ghrelin and GHS-R1a on β or δ cells improved insulin expression. DLS also promoted the glucose-dependent insulin-releasing function of β cells. However, the therapeutic effect of DLS in islet transplantation was fractional. In conclusion, the GHS-R1a antagonist showed preferable effects in improving the therapeutic outcomes of islet transplantation, including the promotion of insulin-releasing function.

Inflammatory Mechanisms in the Pathophysiology of Diabetic Peripheral Neuropathy (DN)—New Aspects

The pathogenesis of diabetic neuropathy is complex, and various pathogenic pathways have been proposed. A better understanding of the pathophysiology is warranted for developing novel therapeutic strategies. Here, we summarize recent evidence from experiments using animal models of type 1 and type 2 diabetes showing that low-grade intraneural inflammation is a facet of diabetic neuropathy. Our experimental data suggest that these mild inflammatory processes are a likely common terminal pathway in diabetic neuropathy associated with the degeneration of intraepidermal nerve fibers. In contrast to earlier reports claiming toxic effects of high-iron content, we found the opposite, i.e., nutritional iron deficiency caused low-grade inflammation and fiber degeneration while in normal or high non-heme iron nutrition no or only extremely mild inflammatory signs were identified in nerve tissue. Obesity and dyslipidemia also appear to trigger mild inflammation of peripheral nerves, associated with neuropathy even in the absence of overt diabetes mellitus. Our finding may be the experimental analog of recent observations identifying systemic proinflammatory activity in human sensorimotor diabetic neuropathy. In a rat model of type 1 diabetes, a mild neuropathy with inflammatory components could be induced by insulin treatment causing an abrupt reduction in HbA1c. This is in line with observations in patients with severe diabetes developing a small fiber neuropathy upon treatment-induced rapid HbA1c reduction. If the inflammatory pathogenesis could be further substantiated by data from human tissues and intervention studies, anti-inflammatory compounds with different modes of action may become candidates for the treatment or prevention of diabetic neuropathy.

Opinions About the Most Appropriate Surgical Management of Diabetes-Related Foot Infection: A Cross-Sectional Survey

Background: There is a lack of high quality evidence to guide the optimal management of diabetes-related foot infection, particularly in severe cases of diabetes-related foot infection and diabetes-related foot osteomyelitis. This study examined the opinions of surgeons about the best management of severe diabetes-related foot infection. Methods: Vascular and orthopaedic surgeons in Australia and New Zealand were invited to complete an online survey via email. The survey included multi-choice and open-ended questions on clinical management of diabetes-related foot infection. Responses of vascular surgeons and orthopaedic surgeons were compared using non-parametric statistical tests. Open-text responses were examined using inductive content analysis. Results: 29 vascular and 20 orthopaedic surgeons completed the survey. One-third (28.6%) used best-practice guidelines to assist in decisions about foot infection management. Areas for guideline improvement identified included more specific advice regarding the indications for available treatments, more information about the overall non-surgical patient management and advice on how management can be varied in regions with limited health service resource. The probe-to-bone test and magnetic resonance imaging were the preferred methods of diagnosing osteomyelitis. Approximately half (51.2%) of respondents indicated piperacillin combined with Tazobactam as the preferred antibiotic choice for empirical treatment of severe diabetes-related foot infection. Negative pressure wound therapy was the most common way of managing a wound following debridement. All vascular surgeons (100%) made revascularisation decisions based the severity of ischemia while most orthopaedic surgeons (66.7%) were likely to refer to vascular surgeons to make revascularisation decisions. Vascular surgeons preferred using wound swabs while orthopaedic surgeons favoured tissue or bone biopsies to determine the choice of antibiotic. Respondents perceived a moderate variation in management decisions between specialists and supported the need for further trials to test different management pathways. Conclusions: Most vascular and orthopaedic surgeons do not use best-practice guidelines to assist in decisions about management of diabetes-related foot infection. Vascular and orthopaedic surgeons appear to have different preferences for wound sampling to determine choice of antibiotic. There is a need to advance available evidence supporting different treatments and the related guidelines for the surgical managing of diabetes-related foot infection.

The Possibility of Adiponectin in Islet Transplantation

Islet transplantation (ITx), a promising therapy for severe diabetes mellitus, needs further evolution. Adiponectin, an adipokine that regulates lipid and glucose metabolism, has some benefits that may improve (e.g., reinforcement of insulin-releasing function). This study attempted to evaluate the possibility of adiponectin for ITx improvement. Mouse islets were treated with 10 µg/mL recombinant mouse adiponectin by overnight culture (defined as adiponectin (+)). The islets’ insulin-releasing, angiogenic, and adhesion functions were assessed and compared with islets without adiponectin treatment (adiponectin (−)). Furthermore, 80 syngeneic islets, with or without adiponectin treatment, were transplanted into the renal subcapsular space of diabetic mice. In vitro assessment showed improved insulin-releasing, angiogenic, and adhesion functions adiponectin (+). Moreover, released insulin volume at high glucose stimulation, insulin content, and expressions of vascular endothelial growth factor and integrin β1 were improved in islets with adiponectin treatment. Furthermore, the ITx therapeutic effect with adiponectin treatment was partial. There was a significant improvement in blood glucose levels in adiponectin (+). No significant differences were noted in plasma insulin and area under the curve of blood glucose level in glucose tolerance test. In conclusion, adiponectin has various usefulness for improving ITx outcomes. Thus, further studies are necessary for this possibility.

Functional Predictors of Treatment Induced Diabetic Neuropathy (TIND): a Prospective Pilot Study Using Clinical and Neurophysiological Functional Tests

Background: A sudden drop of HbA1c has been linked to TIND. Method: From 60 recruited patients with severe diabetes only 21 patients adhered to the study protocol over one year with autonomic nervous system tests before and after antidiabetic treatment initiation. Results: With a pronounced drop of HbA1c some parameters tended to deteriorate with later improvement. Conclusion: Poor adherence appears as major obstacle in this type of study.Trial registration: Ethic Committee University of Leipzig 439/15-ek. Registered 22 April 2016

Personal Mastery and All-Cause Mortality among Older Americans Living with Diabetes

Introduction: Higher personal mastery is associated with better physical functioning, wellbeing, and longevity among older populations. However, few studies have focused on whether personal mastery is protective against mortality among older adults living with diabetes over time. Methods: A total of 1,779 participants were identified from an off-year survey of the Health and Retirement Study. Proportional Hazard Models were used to evaluate the significance of selected variables in predicting the survival of participants over a 13-year period. Results: A substantial proportion (46.7%) of the diabetic patients had survived by the end of 2016. Adults with lower mastery scores were more likely to die (Hazard Ratio = .94, p < .001). Gender differences in the association patterns between personal mastery and survival were identified. Personal mastery had an independent health-protective effect on the survival of diabetes patients over the study period. With lower educational attainment, the foreign-born female diabetics scored higher in personal mastery measure when compared to their male counterparts. In the face of more severe diabetes comorbidity, foreign-born female diabetics also outlived their male counterparts over the study period. Conclusion: As a crucial psychological resource and a modifiable factor, personal mastery holds a potential for improving the health status among lower SES groups of older adults. Further investigations into the identified gender difference could be applied to break the cycle of poor health among lower Socio-Economic Status groups of older adults.

A patient with atrial fibrillation and diabetes: selecting the optimal anticoagulant therapy regimen

Atrial fibrillation (AF) is a common arrhythmia in patients with type 2 diabetes (T2D). Patients with diabetes are at higher risk of AF than those without it. There is an increased risk of dysglycemia in AF. Patients with AF and concomitant diabetes are more likely to have coronary artery disease, hypertension, heart failure, while strokes in patients with AF and diabetes are more severe. Diabetes, in turn, causes the angiopathies and cardiopathy. There is a higher risk of both thrombotic and bleeding events in patients with AF and T2D. The article discusses the mutual burden of T2D and AF, as well as the risk scores for thrombotic, thromboembolic, and bleeding events. Anticoagulant therapy takes a special place in improving the prognosis in AF patients. Numerous studies and actual clinical practice have demonstrated the effectiveness of anticoagulants in the prevention of stroke and other comorbidities.