Diabetes Therapy Research Articles

Okulistyczne aspekty terapii inhibitorami kotransportera sodowo-glukozowego 2. (SGLT-2) – nową grupą leków hipoglikemizujących

Sodium glucose cotransporter 2 is the major protein responsible for glucose reabsorption in the kidneys. Its inhibitors – gliflozins – constitute a new group of hypoglycaemic drugs. The aim of the study is a literature review of ophthalmic aspects of diabetes therapy with the use of this newly introduced group of drugs. Literature data report the expression of the sodium glucose cotransporter 2 not only in the kidneys, but also in non-renal tissues, e.g. in the retina and the lens. Moreover, they indicate its participation in the pathogenesis of diabetic retinopathy. In turn, sodium glucose cotransporter 2 inhibitors, according to the available literature, reduce edema and reduce the loss of pericytes of the retina, and thus may prevent pathological changes occurring in the retina in the course of diabetic retinopathy. The results of clinical trials provide evidence of their effectiveness in the treatment of ocular complications of diabetes, i.e. in preventing the development of diabetic retinopathy, reducing diabetic macular edema, and even inhibiting cataract progression. In addition, the literature provides evidence suggesting a beneficial effect of this new group of hypoglycemic drugs on diabetic retinopathy beyond the control of concentration of blood glucose per se, such as 1. improved energy metabolism, reduction of hypoxia, anti-inflammatory and anti-oxidant effects in the retina by inducing mild ketonemia, 2. as well as a reduction of production of reactive oxygen species via the ERK/1/2/cPLA2/AA/ROS cell pathway. Due to the innovativeness of the topic, the number of literature data in its scope is limited. Therefore, it should be keep in mind that the conclusions may not be complete.

DrCORRECT: An Algorithm for the Preventive Administration of Postprandial Corrective Insulin Boluses in Type 1 Diabetes Management.

In type 1 diabetes therapy, precise tuning of postprandial corrective insulin boluses (CIBs) is crucial to mitigate hyperglycemia without inducing dangerous hypoglycemic events. Several heuristic formulas accounting for continuous glucose monitoring (CGM) trend have been proposed in the literature. However, these formulas suggest a lot of quantized CIB adjustments, and they lack personalization. drCORRECT algorithm proposed in this work employs a patient-specific time parameter and the "dynamic risk" (DR) measure to determine postprandial CIB suggestion. The expected benefits include the reduction of time in hyperglycemia, thanks to the preventive action exploited through DR. drCORRECT has been assessed retrospectively vs the literature methods proposed by Aleppo et al (AL), Bruttomesso et al (BR), and Ziegler et al (ZI) using a data set of 49 CGM daily traces recorded in free-living conditions. Retrospective evaluation of the algorithms is made possible by the use of ReplayBG, a digital twin-based tool that allows assessing alternative insulin therapies on already collected glucose data. Efficacy in terms of glucose control was measured by temporal, risk indicators, and dedicated hyperglycemic/hypoglycemic events metrics. drCORRECT significantly reduces time spent in hyperglycemia when compared with AL and BR (33.52 [24.16, 39.89]% vs 39.76 [22.54, 48.15]% and 36.32 [26.91, 45.93]%, respectively); significantly reduces daily injected insulin (5.97 [3.80, 8.06] U vs 7.5 [5.21, 10.34] U), glycemia risk index (38.78 [26.58, 55.39] vs 40.78 [27.95, 70.30]), and time spent in hypoglycemia (0.00 [0.00, 1.74]% vs 0.00 [0.00, 10.23]%) when compared with ZI, resulting overall in a safer strategy. The proposed drCORRECT algorithm allows preventive actions thanks to the personalized timing configuration and the introduction of the innovative DR-based CIB threshold, proving to be a valid alternative to the available heuristic literature methods.

The potentials of Robusta (Coffea Robusta L.) and Arabica (Coffea Arabica L.) coffee leaf by-product as anti-diabetic drinks

1) Background: It has been known that coffee leaf contain various bioactives and antioxidants. While diabetes can be indicated by the damage of pancreatic beta cells, numerous studies have reported that many kinds of antioxidants can recover the beta cells. As a result, coffee leaf tea has the potential to be developed as an anti-diabetic beverage. The current study used in vivo experiments to investigate the functionality of coffee leaf tea for diabetic therapy; 2) Methods: Robusta and Arabica coffee leaf were processed as oolong tea. All samples were soft-infused. Healthy and diabetic rats (induced with STZ intraperitonially at 80 mg/kg BW) were treated by injecting the softly infused coffee leaf tea 12 ml/kg BW/day for 28 days; 3) Results: Compared to the glibenclamide treatment, diabetic rats injected with Robusta coffee leaf tea were better at lowering blood sugar (p-value <0.05), as well as maintaning body weight. This is supported by the fact that the number of pancreatic beta cells in diabetic rats injected with Robusta coffee leaf tea was significantly higher than in glibenclamide treated rats (pvalue <0.05). Coffee leaf tea tend to have a lighter sensory profile than oolong tea; 4) Conclusions: It can be concluded that Robusta coffee leaf tea tends to be potentially developed as anti-diabetic drink since it can recover damaged pancreatic beta cells better than glibenclamide, thus helping to decrease blood sugar.

Патогенез, ангиогенез диабетического макулярного отека и общая характеристика его лечения (Обзор литературы. Часть I)

Currently, the increase in the prevalence of diabetes mellitus is in the nature of a pandemic. Diabetic macular edema is a vision-threatening complication of diabetic retinopathy, the pathogenesis of which is multifactorial and includes hyperglycemia, endothelial dysfunction, leukostasis and inflammation, vasoconstriction and occlusion, oxidative stress and ischemia, neovascularization, which leads to the accumulation of exudative fluid, thickening of the central zone of the retina and irreversible processes of photoreceptors neurodegeneration with a significant decrease in visual functions. The article presents up-to-date information on the epidemiology, patho- and angiogenesis of this condition as well as the general characteristics of the DMO therapy. It consists of primary treatment of diabetes, laser photocoagulation and anti-angiogenic therapy. Intravitreal drug therapy based on VEGF inhibitors is currently the standard first-line treatment for DMO. The authors emphasize the necessity for further study of trigger points in the pathogenesis of diabetic retinopathy and the development of diabetic macular edema in order to find new drugs and work out a more individualized approach to patients. Key words:: diabetic retinopathy, diabetic macular edema, vascular endothelial growth factor, VEGF-therapy

Novel Therapies in Diabetes: A Comprehensive Narrative Review of GLP-1 Receptor Agonists, SGLT2 Inhibitors, and Beyond.

Diabetes mellitus, a widespread metabolic illness with increasing global occurrence, continues to have a significant impact on public health. Diabetes is a condition marked by long-term high blood sugar levels. It is caused by a combination of genetic, environmental, and lifestyle factors, which lead to problems with insulin production and insulin resistance. This dysfunctional state disturbs the delicate balance of glucose regulation, promoting the emergence of problems in both large and small blood vessels that have a substantial impact on illness and death rates. Traditional therapy methods have traditionally given more importance to managing blood sugar levels by using insulin sensitizers, secretagogues, and other medications that lower glucose levels. Advancements in our understanding of the underlying mechanisms of diabetes have led to a significant change in approach, focusing on comprehensive therapies that target not only high blood sugar levels but also the accompanying dangers to the heart and kidneys. This study examines the evolving field of diabetes therapies, explicitly highlighting the significance of GLP-1 receptor agonists and SGLT2 inhibitors. These two types of drugs have become essential components in modern diabetes management. GLP-1 receptor agonists replicate the effects of natural glucagon-like peptide-1, leading to insulin production that is reliant on glucose levels, reducing the release of glucagon, and providing cardiovascular advantages that go beyond controlling blood sugar levels. SGLT2 inhibitors, however, act on the process of renal glucose reabsorption, leading to increased excretion of glucose in the urine and showing significant benefits for cardiovascular and renal protection. This extensive investigation seeks to contribute to the ongoing discourse on diabetes therapies by synthesizing existing research. This review aims to provide clinicians, researchers, and policymakers with a comprehensive understanding of the disease background and the specific pharmacological details of GLP-1 receptor agonists, SGLT2 inhibitors, and other related treatments. The goal is to assist them in developing more effective and personalized strategies to tackle the complex challenges presented by diabetes.

α-glucosidase and α-amylase inhibitory activity of flavonols from Stenochlaena palustris (Burm.f.) Bedd

Stenochlaena palustris (Burm.f.) Bedd., a fern species native to India, Southeast Asia, Polynesia, and Australia, has a long history of medical including as a diabetic therapy. This study aimed to isolate bioactive compounds from S. palustris ethyl acetate extract and assess their in vitro and in silico inhibitory activities against α-glucosidase and α-amylase. The successful separation of five flavonols, namely stenopalustroside A (1), tiliroside (2), kaempferol (3), quercetin (4), and rutin (5), was achieved through phytochemical analysis. The compounds exhibited a range of inhibitory activities against α-glucosidase and α-amylase, with IC50 values ranging from 40 to 250 µg/mL. Notably, the biological activities of compound 1 have been reported for the first time. Compound 4 was the most effective inhibitor of both enzymes among the isolated compounds. Studies performed in silico reveal that the interactions between amino acids in compounds 4 and 5 are remarkably comparable to those observed in the positive control. These compounds share this commonality, and as a result, they both have the potential to be active agents.

Renewable Human Cell Model for Type 1 Diabetes Research: EndoC-βH5/HUVEC Coculture Spheroids.

In vitro drug screening for type 1 diabetes therapies has largely been conducted on human organ donor islets for proof of efficacy. While native islets are the ultimate target of these drugs (either in situ or for transplantation), significant benefit can be difficult to ascertain due to the highly heterogeneous nature of individual donors and the overall scarcity of human islets for research. We present an in vitro coculture model based on immortalized insulin-producing beta-cell lines with human endothelial cells in 3D spheroids that aims to recapitulate the islet morphology in an effort towards developing a standardized cell model for in vitro diabetes research. Human insulin-producing immortalized EndoC-βH5 cells are cocultured with human endothelial cells in varying ratios to evaluate 3D cell culture models for type 1 diabetes research. Insulin secretion, metabolic activity, live cell fluorescence staining, and gene expression assays were used to compare the viability and functionality of spheroids composed of 100% beta-cells, 1 : 1 beta-cell/endothelial, and 1 : 3 beta-cell/endothelial. Monoculture and βH5/HUVEC cocultures formed compact spheroids within 7 days, with average diameter ~140 μm. This pilot study indicated that stimulated insulin release from 0 to 20 mM glucose increased from ~8-fold for monoculture and 1 : 1 coculture spheroids to over 20-fold for 1 : 3 EndoC-βH5/HUVEC spheroids. Metabolic activity was also ~12% higher in the 1 : 3 EndoC-βH5/HUVEC group compared to other groups. Stimulating monoculture beta-cell spheroids with 20 mM glucose +1 μg/mL glycine-modified INGAP-P increased the insulin stimulation index ~2-fold compared to glucose alone. Considering their availability and consistent phenotype, EndoC-βH5-based spheroids present a useful 3D cell model for in vitro testing and drug screening applications.

Analysis of the influence of ketogenic diet on cancer treatment

Cancer cells' metabolic Warburg effect behavior, in which they rely predominantly on aerobic glycolysis, offers a promising opportunity for focused intervention in tumor therapy. Since nutrient oxidation is linked to this metabolic pathway, manipulating one's diet may be a useful method for dealing with tumors. The high-fat, low-carbohydrate composition of the ketogenic diet causes a metabolic condition called ketosis, which is similar to the states of fasting and starvation on the body. The body is coerced into using fat for fuel, which in turn produces ketone bodies that can be used as alternative metabolites in the creation of aerobic energy. Weight loss, epilepsy therapy, and management of diabetes are just a few of the health benefits that have contributed to the ketogenic diet's meteoric rise in popularity. New studies are pointing to the ketogenic diet's promise in the treatment of cancer as well as its more traditional uses. To better utilize the ketogenic diet as a novel approach to cancer treatment and to refine and optimize the existing dietary protocol through scientific inquiry, this paper examines the ketogenic diet's use from an energy perspective and its potential implications in cancer treatment.

Benefits and risks of drug combination therapy for diabetes mellitus and its complications: a comprehensive review.

Diabetes is a chronic metabolic disease, and its therapeutic goals focus on the effective management of blood glucose and various complications. Drug combination therapy has emerged as a comprehensive treatment approach for diabetes. An increasing number of studies have shown that, compared with monotherapy, combination therapy can bring significant clinical benefits while controlling blood glucose, weight, and blood pressure, as well as mitigating damage from certain complications and delaying their progression in diabetes, including both type 1 diabetes (T1D), type 2 diabetes (T2D) and related complications. This evidence provides strong support for the recommendation of combination therapy for diabetes and highlights the importance of combined treatment. In this review, we first provided a brief overview of the phenotype and pathogenesis of diabetes and discussed several conventional anti-diabetic medications currently used for the treatment of diabetes. We then reviewed several clinical trials and pre-clinical animal experiments on T1D, T2D, and their common complications to evaluate the efficacy and safety of different classes of drug combinations. In general, combination therapy plays a pivotal role in the management of diabetes. Integrating the effectiveness of multiple drugs enables more comprehensive and effective control of blood glucose without increasing the risk of hypoglycemia or other serious adverse events. However, specific treatment regimens should be tailored to individual patients and implemented under the guidance of healthcare professionals.

Ghrelin deletion and conditional ghrelin cell ablation increase pancreatic islet size in mice.

Ghrelin exerts key effects on islet hormone secretion to regulate blood glucose levels. Here, we sought to determine whether ghrelin's effects on islets extend to the alteration of islet size and β cell mass. We demonstrate that reducing ghrelin - by ghrelin gene knockout (GKO), conditional ghrelin cell ablation, or high-fat diet (HFD) feeding - was associated with increased mean islet size (up to 62%), percentage of large islets (up to 854%), and β cell cross-sectional area (up to 51%). In GKO mice, these effects were more apparent in 10- to 12-week-old mice than in 4-week-old mice. Higher β cell numbers from decreased β cell apoptosis drove the increase in β cell cross-sectional area. Conditional ghrelin cell ablation in adult mice increased the β cell number per islet by 40% within 4 weeks. A negative correlation between islet size and plasma ghrelin in HFD-fed plus chow-fed WT mice, together with even larger islet sizes in HFD-fed GKO mice than in HFD-fed WT mice, suggests that reduced ghrelin was not solely responsible for diet-induced obesity-associated islet enlargement. Single-cell transcriptomics revealed changes in gene expression in several GKO islet cell types, including upregulation of Manf, Dnajc3, and Gnas expression in β cells, which supports decreased β cell apoptosis and/or increased β cell proliferation. These effects of ghrelin reduction on islet morphology might prove useful when designing new therapies for diabetes.

HLA-DQ8 Supports Development of Insulitis Mediated by Insulin-Reactive Human TCR-Transgenic T Cells in Nonobese Diabetic Mice.

In an effort to improve HLA-"humanized" mouse models for type 1 diabetes (T1D) therapy development, we previously generated directly in the NOD strain CRISPR/Cas9-mediated deletions of various combinations of murine MHC genes. These new models improved upon previously available platforms by retaining β2-microglobulin functionality in FcRn and nonclassical MHC class I formation. As proof of concept, we generated H2-Db/H2-Kd double knockout NOD mice expressing human HLA-A*0201 or HLA-B*3906 class I variants that both supported autoreactive diabetogenic CD8+ T cell responses. In this follow-up work, we now describe the creation of 10 new NOD-based mouse models expressing various combinations of HLA genes with and without chimeric transgenic human TCRs reactive to proinsulin/insulin. The new TCR-transgenic models develop differing levels of insulitis mediated by HLA-DQ8-restricted insulin-reactive T cells. Additionally, these transgenic T cells can transfer insulitis to newly developed NSG mice lacking classical murine MHC molecules, but expressing HLA-DQ8. These new models can be used to test potential therapeutics for a possible capacity to reduce islet infiltration or change the phenotype of T cells expressing type 1 diabetes patient-derived β cell autoantigen-specific TCRs.

Advancing type 2 diabetes therapy with iGlarLixi in older people: Pooled analysis of four randomized controlled trials.

To assess the efficacy and safety of iGlarLixi in older people (≥65 years) with type 2 diabetes (T2D) advancing or switching from oral agents, a glucagon-like peptide-1 receptor agonist (GLP-1RA), or basal insulin. The data of participants aged <65 years and ≥65 years from four LixiLan trials (LixiLan-O, LixiLan-G, LixiLan-L, SoliMix) were evaluated over 26 or 30 weeks. Participants aged <65/≥65 years (n = 1039/n = 497) had a mean baseline body mass index of 31.4 and 30.7 kg/m2 and glycated haemoglobin (HbA1c) concentration of 66 mmol/mol (8.2%) and 65 mmol/mol (8.1%), respectively. Least squares mean HbA1c change from baseline to end of treatment (EOT) was -14.32 mmol/mol (-1.31%) (95% confidence interval [CI] -14.97, -13.77 [-1.37%, -1.26%]) for those aged <65 years and -13.66 mmol/mol (-1.25%) (95% CI -14.54, -12.79 [-1.33%, -1.17%]) for those aged ≥65 years. At EOT, achievement of HbA1c targets was similar between the group aged <65 years and the group aged ≥65 years: <53 mmol/mol (<7%) (59.0% and 56.5%, respectively), <59 mmol/mol (<7.5%) (75.5% and 73.0%, respectively) and <64 mmol/mol (<8%) (83.8% and 84.1%, respectively). The incidence and event rate of American Diabetes Association Level 1 hypoglycaemia during the studies were also comparable between the two groups: 26.7% and 28.2% and 1.7 and 2.1 events per patient-year for the group aged <65 years and the group aged ≥65 years, respectively. A clinically relevant reduction in HbA1c (>1%from baseline for HbA1c ≥64 mmol/mol [≥8%] or ≥0.5%from baseline for HbA1c <64 mmol/mol [<8%]) without hypoglycaemia was attained by 50.0% and 47.6% of participants aged <65 years and ≥65 years, respectively. Adverse events were similar between the two age groups. iGlarLixi is a simple, well-tolerated, once-daily alternative for treatment advancement in older people with T2D that provides significant improvements in glycaemic control without increasing hypoglycaemia risk, thus reducing the treatment burden.

Real-world lived experience of older adults with type 1 diabetes after an automated insulin delivery trial.

First-generation closed-loop automated insulin delivery improves glycaemia and psychosocial outcomes among older adults with type 1 diabetes in clinical trials. However, no study has previously assessed real-world lived experience of older adults using closed-loop therapy outside a trial environment. Semi-structured interviews were conducted with older adults who were pre-existing insulin pump users and previously completed the OldeR Adult Closed-Loop (ORACL) randomised trial. Interviews focused on perceptions of diabetes technology use, and factors influencing decisions regarding continuation. Twenty-eight participants, mean age 70 years (SD 5), were interviewed at median 650 days (IQR 608-694) after their final ORACL trial visit. At interview, 23 participants (82%) were still using a commercial closed-loop system (requiring manual input for prandial insulin bolus doses). Themes discussed in interviews relating to closed-loop system use included sustained psychosocial benefits, cost and retirement considerations and usability frustrations relating to sensor accuracy and system alarms. Of the five participants who had discontinued, reasons included cost, continuous glucose monitoring-associated difficulties and usability frustrations. Cost was the largest consideration regarding continued use; most participants considered the increased ease of diabetes management to be worth the associated costs, though cost was prohibitive for some. Almost 2 years after completing a closed-loop clinical trial, closed-loop automated insulin delivery remains the preferred type 1 diabetes therapy for the majority of older adult participants. Chronological age is not a barrier to real-world successful use of diabetes technology. Identifying age-related barriers, and solutions, to diabetes technology use among older adults is warranted.

Review on Oral Insulin for Diabetics Mellitus

Oral insulin is one of the most exciting areas of diabetes therapy, due to the potential benefits of patient convenience, liver rapid insulination, appropriate insulin delivery to avoid hyperinsulin hypertension in the peripheral region, and the potential to avoid the harmful effects of weight gain and low blood sugar. Evidence is growing that early intensive insulin therapy leads to sustainable and tight blood glucose control and leads to serious complications, making effective oral insulin products even more important for the treatment of diabetic patients. Despite the knowledge of this medical need, insulin injections have failed due to several obstacles. For decades, researchers have tried to develop oral insulin with various technologies, but have not succeeded in clinical and commercial studies. The review summarizes the development status of oral insulin and indicates that it is under clinical trial

Experience of Diabetic Patients for the Usage of Complementary and Alternative Medicine Therapy

Background: Diabetes is common in every community, but its management always seems to be challenging. The alternative medicine (AM) therapies in multiple ways have been widely accepted by individuals suffering from various diseases. This study was undertaken to evaluate the knowledge and experience of diabetic patients towards the implication of multiple AM therapies. Methods: This study aimed to investigate the knowledge and experiences of diabetic patients regarding the use of various alternative medicine therapies. Data were collected through a self-administered questionnaire, and statistical software SPSS was employed for data analysis. Results: Out of 469 diabetic patients, 123 were diagnosed with type 1 diabetes, 333 had type 2 diabetes, and the remaining patients had gestational diabetes. A majority of the diabetic patients (61.3%) reported that combining alternative medicine (AM) with allopathic diabetic medicines effectively controlled their blood sugar levels. Interestingly, 64.7% of patients received recommendations from diabetologists to incorporate AM therapies into their treatment plans. Among all diabetic patients, 85.3% believed that AM therapies had no side effects. Herbal medicines/herbs were favored by 28.7% of diabetic patients, while 15.4% and 14.5% reported experiencing the effectiveness of homeopathy and yoga, respectively, for diabetic therapy. Conclusion: This comprehensive study reveals the potential of alternative medicine therapies in managing diabetes. However, it emphasizes the importance of exercising caution when relying solely on specific complementary and alternative medicine approaches during the follow-up process.

Melatonin supports nonsurgical periodontal treatment in patients with Type 2 diabetes mellitus and periodontitis: A randomized clinical trial.

Diabetes mellitus (DM)-associated hyperinflammatory host response significantly provokes periodontal tissue destruction. In this context, the support of nonsurgical periodontal therapy in diabetics with host modulation agents is a current field of study. This clinical study aims to investigate the clinical efficacy of melatonin supplementation and discuss its possible biological mechanisms in nonsurgical periodontal treatment in patients with DM and periodontitis through some fundamental markers. In this randomized controlled and single-blind study, 27 of 55 diabetic patients with periodontitis (stage III/IV and grade C) underwent full-mouth scaling and root planing (fmSRP) alone and 28 patients underwent melatonin administration (6mg daily, 30days) in addition to fmSRP (full-mouth scaling and root planing plus melatonin, fmSRP-mel). The potential therapeutic contribution of melatonin was evaluated clinically and biochemically (gingival crevicular fluid RANKL, OPG, MMP-8, and serum IL-1β levels) at 3rd and 6th months. Melatonin (tablet, 6mg daily, 30days) did not cause any local or systemic side effects. fmSRP alone resulted in significant reduction in serum IL-1β levels, pocket depths, gingival inflammation, and gingival crevicular fluid RANKL and MMP-8 levels (p<0.05). Moreover, melatonin supplementation resulted in a more significant decrease in bleeding and pocket depth scores at probing, especially at 3months (p<0.05). Furthermore, RANKL and MMP-8 levels were significantly lower at 3months and IL-1β levels at 6months compared to the control group (p<0.05). However, OPG levels were not affected significantly by the treatments (p>0.05). Melatonin, as a host modulation agent, significantly increases the clinical efficacy of fmSRP. The reduction in periodontal inflammation and pocket depths may be a result of marked suppression of RANKL-associated osteoclastogenesis and extracellular matrix damage by melatonin.

Risk factors for spinal subdural hematoma after minimally invasive transforaminal lumbar Interbody Fusion (MI-TLIF): a multivariate analysis

BackgroundSpinal subdural hematoma (SSH) is a rare cause of compression of the neutral elements of the spinal cord. However, little is known about the presentation of acute SSH after lumbar spine surgery. The reason for this may be that symptomatic SSH occurs rarely and is not given enough attention by spine surgeons. Currently, the decision to perform MRI postoperatively is more dependent on surgeon preference; therefore, no high-quality studies have been published. Our team reports our experience in the diagnosis and management of SSH after lumbar decompression and fusion surgery.MethodsWe retrospectively studied 215 patients who underwent routine MRI following minimal invasive transforaminal lumbar interbody fusion (MI-TLIF) between 2020-01-01 and 2022-06-30. The patients were divided into SSH group (17 cases) and non-SSH group (198 cases) according to the occurrence of SSH. Univariate analysis and multivariate logistic regression analysis were performed to identify relevant risk factors that increase the risk of SSH postoperatively.ResultsNone of the patients presented with serious neurologic symptoms, such as lower extremity paralysis or cauda equina syndrome that required emergency hematoma debridement. SSH was found in 17 (7.9%) patients and non-SSH in 198 (92.1%). Factors affecting SSH were presence of hypertension, presence of diabetes and postoperative anticoagulant therapy. The significantly independent risk factor of postoperative SSH were diabetes (P = 0.008, OR: 6.988) and postoperative anticoagulant therapy (P = 0.003, OR: 8.808).ConclusionsSSH after MI-TLIF is not a rare condition, with generally no requirement of emergency evacuation. Comprehensive anti-symptomatic treatment could achieve satisfactory results. Diabetes mellitus and postoperative anticoagulant therapy are independent risk factors for SSH. Spine surgeons should hold applicability of the use of anticoagulants after lumbar surgery.

Inflammation-induced subcutaneous neovascularization for the long-term survival of encapsulated islets without immunosuppression.

Cellular therapies for type-1 diabetes can leverage cell encapsulation to dispense with immunosuppression. However, encapsulated islet cells do not survive long, particularly when implanted in poorly vascularized subcutaneous sites. Here we show that the induction of neovascularization via temporary controlled inflammation through the implantation of a nylon catheter can be used to create a subcutaneous cavity that supports the transplantation and optimal function of a geometrically matching islet-encapsulation device consisting of a twisted nylon surgical thread coated with an islet-seeded alginate hydrogel. The neovascularized cavity led to the sustained reversal of diabetes, as we show in immunocompetent syngeneic, allogeneic and xenogeneic mouse models of diabetes, owing to increased oxygenation, physiological glucose responsiveness and islet survival, as indicated by a computational model of mass transport. The cavity also allowed for the in situ replacement of impaired devices, with prompt return to normoglycemia. Controlled inflammation-induced neovascularization is a scalable approach, as we show with a minipig model, and may facilitate the clinical translation of immunosuppression-free subcutaneous islet transplantation.

Diabetes-correcting and antioxidant effects of grape pomace extract rich in natural complex of polyphenols

Background. The positive health effects of polyphenols have led to an increased scientific interest in these natural compounds over the past decade. Many studies confirm the effectiveness of polyphenols as additional therapy in diabetes, especially due to the sugar-lowering effect of polyphenols. The aim of the research was to investigate the morphological and functional state of peripheral blood erythrocytes and the indices of oxidative stress in the liver of rats with experimental diabetes and after the administration of grape pomace extract rich in natural complex of polyphenols. Materials and Methods. We obtained grape pomace extract, which contains a variety of polyphenolic compounds. Rats of the following groups were used in the experiments: control animals, animals treated with grape pomace extract rich in natural complex of polyphenols for 14 days, animals with streptozotocin-induced diabetes mellitus, and animals with streptozotocin-induced diabetes mellitus treated with grape pomace extract rich in natural complex of polyphenols for 14 days. The number of erythrocytes and reticulocytes, the concentration of hemoglobin and glycated hemoglobin were determined in the peripheral blood of rats. The activities of catalase, superoxide dismutase and the content of thiobarbituric acid-reactive substance and carbonyl groups of proteins were determined in the liver tissues of rats. Results. The study has shown an increase in the number of erythrocytes and the level of hemoglobin, a decrease in the level of glycated hemoglobin and the number of reticulocytes in the peripheral blood of rats after administration of grape pomace extract rich in natural complex of polyphenols to rats with experimental diabetes. A decrease in the content of thiobarbituric acid-reactive substance and the content of carbonyl groups of proteins of neutral and basic character and an increase in the activity of catalase and superoxide dismutase in liver tissues were found under the same conditions. Conclusions. The results indicate that the extract of the natural complex of polyphenols is capable of correcting the morphological and functional state of erythrocytes, as well as improving the activity of antioxidant enzymes and the content of marker molecules of oxidative stress in hepatocytes of rats under experimental diabetes mellitus.

Role and Significance of Dietary Protein in the Management of Type 2 Diabetes and Its Complications in India: An Expert Opinion.

Obesity, prediabetes, and type 2 diabetes mellitus (T2DM) pose a triple burden in India. Almost two-thirds of people with diabetes (PWD) in India are found to have suboptimal glycemic, blood pressure, and lipid control. Medical nutrition therapy (MNT) in diabetes has emphasized on the amount and type of carbohydrates for years. However, protein, an important macronutrient in diabetes management, needs to be focused upon, especially in India, where the consumption is found to be lower than the recommendations provided by most guidelines. An expert committee attempted to review the role of dietary protein in the management of T2DM, arrive at a consensus on the significance of increasing dietary protein for various benefits, and offer practical guidance on ways to improve protein intake among Indians. A total of 10 endocrinologists and diabetologists, one nephrologist, and three registered dietitians representing four zones of India formed the expert committee. An in-depth review of literature in the Indian context was carried out, and the draft document was shared with the expert committee, and their views were incorporated into the same. The expert committee then assembled virtually to deliberate on various aspects of the role of protein in T2DM management. The experts from various specialties gave their valuable inputs and suggestions from their extensive personal clinical experience and research work, which helped to reach a consensus on the role and significance of protein in the management of T2DM and its complications in India. There is abundant evidence that MNT is essential for the prevention and management of T2DM and its complications. Experts agreed that increasing protein intake offers myriad health benefits, namely reducing glycemic variability, improving glycemic control, increasing insulin sensitivity, improvement in lipid profile and immunity, and helping in weight management and preservation of muscle mass in PWD. The expert committee suggested aiming for an increase in protein intake by at least 5-10% of the current intake in lieu of carbohydrates in PWD. Experts also highlighted the need for more data quantifying the unmet protein needs in the Indian PWD, especially among vegetarians. Randomized controlled trials to study the effect of protein in diabetes complications such as cardiovascular disease (CVD) and diabetic kidney disease (DKD) and comorbid conditions such as sarcopenia among the Indian population are also warranted. Increasing protein quantity and quality in the diets of Indian PWD could significantly contribute to positive health outcomes. Increased protein intake, preferably through dietary sources to meet the requirements and, when required using diabetes-specific protein supplements (DSPS), is recommended in the prevention and control of T2DM.