Role of Synbiotics (Prebiotics and Probiotics) as Dietary Supplements in Type 2 Diabetes Mellitus Induced Health Complications.

Diabetes is a metabolic disorder whose prevalence has become a worrying condition in recent decades. Chronic diabetes can result in serious health conditions such as impaired kidney function, stroke, blindness, and myocardial infarction. Despite a variety of currently available treatments, cases of diabetes and its complications are on the rise. This review article provides a comprehensive account of the ameliorative effect of prebiotics and probiotics individually or in combination i.e. synbiotics on health complications induced by Type 2 Diabetes Mellitus (T2DM). Recent advances in the field underscore encouraging outcomes suggesting the consumption of synbiotics leads to favorable changes in the gut microbiota. These changes result in the production of bioactive metabolites such as short-chain fatty acids (crucial for lowering blood sugar levels), reducing inflammation, preventing insulin resistance, and encouraging the release of glucagon-like peptide-1 in the host. Notably, novel strategies supplementing synbiotics to support gut microbiota are gaining attraction as pivotal interventions in mitigating T2DM-induced health complications. Thus, by nurturing a symbiotic relationship between prebiotics and probiotics i.e. synbiotics, these interventions hold promise in reshaping the microbial landscape of the gut thereby offering a multifaceted approach to managing T2DM and its associated morbidities. Supporting the potential of synbiotics underscores a paradigm shift toward holistic and targeted interventions in diabetes management, offering prospects for improved outcomes and enhanced quality of life for affected individuals. Nevertheless, more research needs to be done to better understand the single and multispecies pre/pro and synbiotics in the prevention and management of T2DM-induced health complications.

Improved prognosis with integrated care management including early rhythm control and healthy lifestyle modification in patients with concurrent atrial fibrillation and diabetes mellitus: a nationwide cohort study.

BACKGROUND: Patients with concurrent atrial fibrillation (AF) and diabetes mellitus (DM) [AF-DM] have a high risk of cardiovascular and diabetes-related complications, but are less engaged in a comprehensive treatment approach. We evaluated the association of early rhythm control (ERC), lifestyle modification (LSM), and a combination of ERC and LSM with cardiovascular or diabetes-related complication risk in patients with AF-DM (type 2). METHODS: From the National Health Information Database, 47,940 patients diagnosed with AF-DM in 2009-2016 were included. We defined ERC as rhythm control therapy within two years of AF diagnosis and LSM as adherence to ≥ 2 of the healthy behaviors among non-current smoking, non-drinking, and regular exercise. We compared the primary (ischemic stroke) and secondary (macro- and microvascular complications, glycemic emergency, and all-cause death) outcomes in four groups: non-ERC and non-LSM (group 1), LSM only (group 2), ERC only (group 3), and both ERC and LSM (group 4). RESULTS: Of total, 10,617 (22%), 26,730 (55.8%), 2,903 (6.1%), and 7,690 (16.0%) were classified into groups 1 to 4, in sequence. The mean duration from AF diagnosis to ERC was 25.6 ± 75.5 days. During 4.0 (interquartile range: 2.5-6.2) years' follow-up, groups 2 and 3 were associated with 23% and 33% lower risks of stroke than group 1, respectively. Group 4 was associated with the lowest risk of stroke: hazard ratio (HR) 0.58, 95% confidence interval (CI) 0.51-0.67, p < 0.001. Regarding secondary outcomes, the lowest risks were also observed in group 4; macro- and microvascular complications, glycemic emergency, and all-cause death had HRs (95% CIs) of 0.63 (0.56-0.70), 0.88 (0.82-0.94), 0.72 (0.62-0.84), and 0.80 (0.73-0.87), respectively, all p < 0.001. CONCLUSIONS: For AF-DM patients, ERC and LSM exert a synergistic effect in preventing cardiovascular and diabetes-related complications with the greatest lowered risk of stroke. A comprehensive treatment approach should be pursued in AF-DM patients.

The efficacy and safety of Tuina for diabetic gastroparesis: A protocol for systematic review and meta-analysis.

BACKGROUND: Diabetic gastroparesis (DGP) is one of the most common complication of diabetes. At present, despite the increasing number of clinical researches of treatment with Tuina have been reported, there are no systematic reviews of Tuina therapy for DGP. Therefore, it is of great significance to evaluate its safety and efficacy as a complementary and alternative therapy. METHODS AND ANALYSIS: Randomized controlled trials (RCTs) of Tuina therapy in the treatment of DGP will be retrieved from PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wan Fang Database (Wan Fang), Chinese Biomedical Literature Database (CBM), VIP Database for Chinese Technical Periodicals (VIP), Medline, and Clinical Trial Register (CTR). We will consider articles published in English or Chinese between database initiation and October 2021. Research selection, data extraction, risk of bias assessment, and meta-analyses will be independently completed by 2 researchers. Our researchers will use Revman 5.3 software, provided by the Cochrane Collaborative Network for conducting systematic reviews and meta-analysis. RESULTS: This systematic review provides a high-quality synthesis to assess the effectiveness and safety of Tuina therapy for treating DGP. CONCLUSION: The conclusions of our study will provide evidence to determine whether Tuina therapy is an effective and safe intervention for patients with DGP. SYSTEMATIC REVIEW REGISTRATION: : INPLASY2021110019.

Effects of Stimulating Local and Distal Acupoints on Diabetic Gastroparesis: A New Insight in Revealing Acupuncture Therapeutics.

One of the most important aspects of clinical acupuncture practice, like diabetic gastroparesis, is the selection of suitable acupoints. Furthermore, it is critical to examine the therapeutic impact differences between distal and local acupoints, as well as the prescription of their combination. In this study, diabetic gastroparesis rats were treated by needling Zhongwan (CV12) and Zusanli (ST36), and then used Single Photon Emission Computed Tomography-CT (SPECT-CT) technology to assess the effects of promoting gastric motility. In addition, morphological observation, immunohistochemical examination, and biomarker assays, such as determination of growth factor 1, motilin, and ghrelin contents in serum samples, were performed to better understand the impact of certain various acupuncture treatments. All of the therapies improved the symptoms of diabetic gastroparesis rats, according to the findings. Stimulating these acupoints, on the other hand, can have a different therapeutic effect. In addition, needling local and distal acupoints together can have an antagonistic or synergistic impact on specific physiological and biochemical indexes such as gastric motility, ghrelin, gastrin, and growth factor 1, among others. Our findings demonstrated the benefits of acupoints and acupuncture in the management of diabetic gastroparesis, as well as a new insight into acupuncture therapeutics.

Acupuncture for diabetic neurogenic bladder: A protocol for systematic review and meta-analysis.

BACKGROUND: Diabetic neurogenic bladder (DNB) is one of the common complications of diabetes mellitus, which has a high prevalence rate. Some research suggested that acupuncture can improve the clinical symptoms of diabetic neurogenic bladder patients, but there is no systematic review or meta-analysis to assess this therapy. Therefore, this study aims to explore the effectiveness and safety of acupuncture for patients with DNB. METHODS: In this study, we will search for electronic databases including the Cochrane Library, Web of Science, PubMed, MEDLINE, EMBASE,China National Knowledge Infrastructure (CNKI), Wan-Fang, and Baidu Scholar Database from inception to December 2020. We will select randomized controlled trials that have been published in English or Chinese related to acupuncture for DNB. Selection of study, extraction of data, and assessment of study quality will be performed independently by 2 researchers, and we will use Revman 5.3 software which is provided by Cochrane assistance network, to perform the data analysis. RESULTS: This study will provide evidence of the effectiveness and safety of acupuncture for DNB. CONCLUSION: This study will clarify whether acupuncture is an effective treatment for DNB, and will also provide a reference for clinical practice and guidelines development.

[Diabetic Dyslipidemia]. / Dyslipidämie bei Diabetes.

Diabetic dyslipidemia is a major cause of the increased cardiovascular risk in diabetes. This lipid disorder is characterized by increased plasma triglycerides, increased remnant particles of triglyceride-rich lipoproteins, small dense LDL particles and reduced HDL cholesterol. The main pathogenetic triggers are obesity and insulin resistance. In addition to lifestyle measures, statins, ezetimibe and eventually PCSK9 inhibitors are available to treat diabetic dyslipidemia and to reduce the cardiovascular risk. Fibrates and omega-3 fatty acids currently do not play a significant therapeutic role. A consistent and target-oriented therapy of diabetic dyslipidemia is a prerequisite for a cardiovascular risk reduction in patients with diabetes, which has been well proven in clinical studies.

Efficacy of gastric electrical stimulation in intractable nausea and vomiting at 10 years: A retrospective analysis of prospectively collected data.

BACKGROUND: Gastric electrical simulation has been shown to relieve nausea and vomiting in medically refractory patients. Efficacy of gastric electrical stimulation has been reported mostly in short-term studies, but none has evaluated its efficacy beyond 10 years after implantation. METHODS: Patients implanted at our center for medically refractory severe and chronic nausea and/or vomiting were evaluated before and over 10 years after implantation using symptomatic scale and quality of life (GIQLI) score. Improvement was defined as a reduction of more than 50% in vomiting frequency. KEY RESULTS: A total of 50 patients were implanted from January 1998 to December 2009. Among them, 7 were explanted due to a lack of efficacy and/or side effects, 2 died, and 4 were lost to follow-up. Mean follow-up was 10.5 ± 3.7 years. In intention-to-treat analysis, 27/50 (54%) patients reported an improvement. Beyond 10 years, an improvement in early satiety (3.05 vs 1.76, <0.001), bloating (2.51 vs 1.70, P = .012), nausea (2.46 vs 1.35, P = .001), and vomiting (3.35 vs 1.49 P < .001) scores were observed. Quality of life improved over 10 years (GIQLI score: 69.7 vs. 86.4, P = .005) and body mass index (BMI: 23.4 vs. 26.2 kg/m2 ; P = .048). CONCLUSIONS AND INFERENCES: Gastric electrical simulation is effective in the long-term in patients with medically refractory nausea and vomiting, with an efficacy of 54% at 10 years on an intention-to-treat analysis. Other long-term observational studies are warranted to confirm these results.

[Effect of Tiaoli Piwei needling technique on diabetic gastroparesis and transmembrane protein 16A].

OBJECTIVE: To observe the therapeutic effect of Tiaoli Piwei needling technique (acupuncture for regulating spleen and stomach) on diabetic gastroparesis (DGP), and to explore its possible mechanism. METHODS: A total of 128 patients with DGP were randomized into an observation group (64 cases, 4 cases dropped off) and a control group (64 cases, 4 cases dropped off). On the basis of intervention on controlling blood glucose by western medication, Tiaoli Piwei needling technique was adopted at Zhongwan (CV 12), Zusanli (ST 36), Yinlingquan (SP 9), Xuehai (SP 10), Sanyinjiao (SP 6), Diji (SP 8), etc. in the observation group, once a day. Mosapride citrate dispersible tablet 5 mg was given orally 3 times a day in the control group. The treatment was given 6 times a week in the both groups, and totally 4-week treatment was required. Before and after treatment, the DGP symptom score, serum content of transmembrane protein 16A (ANO1) were observed, and the clinical therapeutic effect and the safety were evaluated in the both groups. RESULTS: After treatment, the each subitem score (belching, abdominal distension, inappetence, nausea and vomiting, epigastric pain, abnormal defecation) and the total score of DGP symptom were decreased in both groups (P<0.05), the subitem scores of belching, abdominal distension, inappetence, nausea and vomiting and the total score in the observation group were lower than those in the control group (P<0.05). After treatment, the serum contents of transmembrane protein 16A were reduced in both groups (P<0.05), and that in the observation group was lower than the control group (P<0.05). The total effective rate was 86.7% (52/60) in the observation group, which was superior to 70.0% (42/60) in the control group (P<0.05). Subcutaneous hematoma occurred in 5 cases in the observation group, which was improved after cold compress without other particular intervention. CONCLUSION: The therapeutic effect of Tiaoli Piwei needling technique on improving symptoms in patients with diabetic gastroparesis is superior to mosapride citrate dispersible tablet, its mechanism may be related to alleviating the damage of interstitial cells of Cajal (ICC).

Curcumin Ameliorate Diabetes type 1 Complications through Decreasing Pro-inflammatory Cytokines in C57BL/6 Mice.

Type 1 diabetes is a chronic autoimmune disease of beta cells in the islets of Langerhans, which are responsible for making insulin. Even with insulin therapy, inflammatory complications will develop in the long term. The present study examines changes in serum levels of interleukin (IL)-6, IL-17, IL-10, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, C-peptide, Insulin as well as fasting blood sugar (FBS) in control, diabetic and diabetic treated with curcumin groups. Thirty inbred C57BL /6 mice were randomly divided into three groups of 10 mice: group A consisted of healthy mice receiving citrate buffer, group B included a group of diabetic mice, and group C was a group of diabetic mice treated with curcumin. The cytokine levels were measured in the supernatant of stimulated splenocytes using enzyme -linked immunosorbent assay (ELISA). Radioimmunoassay was used to measure insulin and c-peptide levels. The FBS was measured by an automatic glucometer device. The levels of IL-6, IL-17, and IFN-γ, as well as FBS, was significantly decreased in the treated group with curcumin compared to the diabetic group mice (p<0.05). TNF-α levels were also low, but the difference was not significant. IL-10, plasma C-peptide, and insulin significantly increased in the supernatant of stimulated splenocytes of treated diabetic group than in the diabetic group (p<0/05). According to the results, this study supports the anti-diabetic and anti-inflammatory effects of curcumin; however, more studies are needed to investigate theeffects of curcumin and the dose-response relationship in this disease.

Possible Involvement of Vitamin C in Periodontal Disease-Diabetes Mellitus Association.

Ascorbic acid (vitamin C) is an important water-soluble vitamin found in many fruits and vegetables. It has well-documented beneficial effects on the human body and is used as a supplement, alone or in combination with other vitamins and minerals. Over recent years, research has focused on possible new therapeutic actions in chronic conditions including periodontal disease (PD). We conducted a systematic review on clinical trials from four databases (PubMed, Clinical Trials, Cochrane, Web of Science) which measured plasmatic/salivary levels of ascorbic acid in PD-diabetes mellitus (DM) association. Six studies were included in our review, three of them analyzing patients with different grades of PD and DM who received vitamin C as a treatment (500 mg vitamin C/day for 2 months and 450 mg/day for 2 weeks) or as part of their alimentation (guava fruits), in combination with standard therapies and procedures. Decreased levels of vitamin C were observed in PD patients with DM but data about efficacy of vitamin C administration are inconclusive. Given the important bidirectional relationship between PD and DM, there is a strong need for more research to assess the positive effects of ascorbic acid supplementation in individuals suffering from both diseases and also its proper regimen for these patients.

Individualized Chinese medicine for the treatment of diabetic patients with dry eye disease: A single-case randomized controlled protocol.

BACKGROUND: The high incidence of Diabetes mellitus (DM) has become a serious challenge for the global epidemic. Increased blood glucose leads to abnormal ocular surface structure and metabolic disorder in patients. DM is a high-risk factor for dry eye disease (DED), with high incidence and increased difficulty in treatment. The disease can cause discomfort, visual impairment, tear film instability and ocular surface damage, and even cause corneal erosion in severe cases, which has a serious impact on people's daily life. Traditional Chinese Medicine (TCM) plays an important role in the evaluation and treatment of DM and its complications. However, whether TCM treatment could improve the treatment efficacy of DM suffering from DED remains poorly understood. OBJECTIVE: To investigate the curative effect of TCM for the alleviation of clinical symptoms in Diabetic patients with DED, and to evaluate its long-term efficacy. METHODS: This trial is a single-case randomized, single-blind, placebo-controlled study. A total of 12 subjects will be recruited in this trial. The trial is divided into three cycles, and one cycle has 2 treatment periods. There is a washout period at each adjacent treatment stage. TCM individualized treatment and placebo will be randomized during the treatment period. The test period will last for 29 weeks, with 4 weeks for each treatment period and 1 week for each washout period to minimize carryover effects. Subjects will be selected by the researcher strictly in accordance with the inclusion and exclusion criteria. The outcomes will evaluate the efficacy of treatment by changes in the various observation indicators. DISCUSSION: This study will realize a patient-centered outcome approach necessary to provide clinical researchers with the evidence that TCM treatment can effectively improve the objective indicators of the eye and systemic symptoms in Diabetic patients with DED. TRIAL REGISTRATION: This study has been registered at the Chinese Clinical Trial Registry (http://www.chictr.org.cn, No. ChiCTR1900024481), (October, 2019).

Asiaticoside nitric oxide gel accelerates diabetic cutaneous ulcers healing by activating Wnt/ß-catenin signaling pathway.

Diabetic ulcers, gangrene, local infections and other traumatic symptoms of wound healing are all directly related. Promoting the early healing of diabetic cutaneous ulcers (DCU) and reducing the disability and treatment costs is an important research project integrating traditional Chinese and Western medicine. Nitric oxide (NO) is a key component of wound healing, and endogenous NO secretion is insufficient during the development of DCU. It has been reported that exogenous NO can promote wound healing, but exogenous NO has a short half-life and is difficult to adhere to the skin. Asiaticoside (AC) is extracted from the traditional Chinese medicine Centella asiatica, and has angiogenic, anticancer, antioxidant, anti-inflammatory, and wound-healing effects. Therefore, our study is based on the hypothesis that the combination of AC and NO to treat DCU is possible. In this study we considered gels of AC and NO, and evaluated the effects of the gel on DCU healing. Based on our study, it was found that the combined effect of asiaticoside and NO could accelerate the healing rate of DCU wounds. The asiaticoside NO gel can inhibit the growth of bacteria in the wound surface, alleviate the inflammatory reaction of wound, and increase the expression of VEGF, iNOS, eNOS and CD34. Our research shows that asiaticoside NO gel may promote DCU wound healing by regulating Wnt/ß-Catenin signaling pathway. It will provide new targets and strategies for the diagnosis and treatment of DCU.

African Plants with Antidiabetic Potentials: Beyond Glycaemic Control to Central Nervous System Benefits.

BACKGROUND: For centuries, humans have used medicinal plants in the management of both acute and chronic diseases. Currently, the practice of using medicinal plants to manage diseases is becoming increasingly-common; especially in medium to low-income economies where the cost of, or ease of access to orthodox medications are limitations to their effective and sustained use. Diabetes mellitus is a chronic disease whose prevalence continues to increase worldwide. An aspect of diabetes mellitus that causes significant morbidity is its neurological complications, which are known to be associated with an enormous economic burden and reduction in quality of life. OBJECTIVES: While research continues to demonstrate that a wide range of plants that are indigenous to Africa have significant antihyperglycaemic properties, scientific information on the neurobehavioural and/or neuromorphological effects of these plants appear to be lacking. Also, their possible benefits in the prevention or amelioration of the neurological complications of diabetes mellitus remain generally unexamined. METHODOLOGY: In this narrative review, we the examine available scientific literature dealing with the neurobehavioural and/or neuromorphological profiles of selected African plants with substantiated antihyperglycaemic properties; aiming to highlight their potential applications in the prevention and management of the neurological complications of diabetes mellitus. RESULTS: This review demonstrates that a number of the African plants with antidiabetic properties also exhibit central nervous system effects. CONCLUSION: While the neurobehavioural and neuromorphological effects of some of these plants had been investigated in animal models of DM; their possible roles in the prevention or amelioration of the neurological complications of DM are yet to be established.

Effect of Hyperbaric Oxygen Therapy on Fatty Acid Composition and Insulin-like Growth Factor Binding Protein 1 in Adult Type 1 Diabetes Mellitus Patients: A Pilot Study.

OBJECTIVE: Metabolic changes in type 1 diabetes mellitus (T1DM) impair vasodilation, and this leads to tissue hypoxia and microvascular pathology. Hyperbaric oxygen therapy (HBOT) can significantly improve the outcome of ischemic conditions in T1DM patients and reduce vascular complications. The aim of our study was to assess the effects of HBOT on plasma fatty acid (FA) composition, and expression of insulin-like growth factor binding protein 1 (IGFBP-1) in T1DM patients. METHODS: Our study included 24 adult T1DM patients diagnosed with peripheral vascular complications. The patients were exposed to 10 sessions of 100% oxygen inhalation at 2.4 atmosphere absolute for 1 hour. Blood samples were collected at admission and after HBOT for measurement of metabolic parameters, FA composition and IGFBP-1. Measurement of plasma FA composition was determined by gas chromatography. Expression of IGFBP-1 in the serum was estimated by Western blot analysis. RESULTS: HBOT decreased blood levels of total cholesterol (p<0.05), triglycerides (p<0.05) and low-density lipoprotein (p<0.05). HBOT increased plasma levels of individual FAs: palmitic acid (p<0.05), palmitoleic acid (p<0.05), docosapentaenoic acid (p<0.05) and docosahexaenoic acid (p<0.01), and decreased levels of stearic acid (p<0.05), alpha linolenic acid (p<0.05) and linoleic acid (p<0.01). Expression of IGFBP-1 (p<0.01) was increased, whereas the level of insulin (p<0.001) was decreased in the serum after HBOT. CONCLUSIONS: Our results indicate that HBOT exerts beneficial effects in T1DM patients by improving the lipid profile and altering FA composition.

Acupoint catgut embedding for diabetic gastroparesis: A protocol of systematic review.

BACKGROUND: Diabetic gastroparesis (DG) is a common complication to diabetes mellitus (DM). A lot of clinical researches have focused on acupoint catgut embedding for diabetic gastroparesis. However, there is no systematic review and meta-analysis has been conducted. We aim to systematically review the effect of acupoint catgut embedding on diabetic gastroparesis. METHODS: The databases including PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, Ovid LWW, EMBASE, CNKI, Wanfang Database will be searched. Studies published from the time when the database establishment to July 2019 will be retrieved. Randomized controlled clinical trials and quasi-randomized controlled trials on acupoint catgut embedding for diabetic gastroparesis will be included. The primary outcomes are gastroparesis Cardinal Symptom Index (GCSI) or a similar scale to score dyspeptic symptoms. RevMan V.5.3 software will be used to perform the analyses. RESULTS: This study will provide a high-quality synthesis of the effectiveness and safety of acupoint catgut embedding for diabetic gastroparesis. CONCLUSION: This systematic review will provide a high-quality evidence to judge whether the acupoint catgut embedding is beneficial to treat diabetic gastroparesis. PROSPERO REGISTRATION NUMBER: CRD42019140951.

Patient and Health Care Factors Associated With Long-term Diabetes Complications Among Adults With and Without Mental Health and Substance Use Disorders.

Importance: Among people with diabetes, co-occurring mental health (MH) or substance use (SU) disorders increase the risk of medical complications. Identifying how to effectively promote long-term medical benefits for at-risk populations, such as people with MH or SU disorders, is essential. Knowing more about how health care accessed before the onset of diabetes is associated with health benefits after the onset of diabetes could inform treatment planning and population health management. Objective: To analyze how preexisting MH or SU disorders and primary care utilization before a new diabetes diagnosis are associated with the long-term severity of diabetes complications. Design, Setting, and Participants: This cohort study analyzed medical record data from US Department of Veterans Affairs health care systems nationwide and used mixed-effects regressions to test associations between prediabetes patient or health care factors and longitudinal progression of diabetes complication severity from 2006 to 2015. Participants included patients who received a new diabetes diagnosis in 2008 and who were aged 18 to 85 years at the time of their diagnosis. Data analysis was conducted from March to August 2017. Exposures: Patients were assigned to groups on the basis of a 2-year look-back period for MH or SU disorders status (MH disorder only, SU disorder only, MH and SU disorder, or no MH or SU disorder diagnoses) and on the basis of the amount of primary care utilization before diabetes was diagnosed. Main Outcomes and Measures: Nine-year trajectories of Diabetes Complication Severity Index (DCSI) scores. Results: Among 122 992 patients with newly diagnosed diabetes, the mean (SD) age was 62.3 (11.1) years, 118 810 (96.6%) were male, and 28 633 (23.3%) had preexisting MH or SU disorders diagnoses. From the onset of diabetes to 7 years later, patients' mean estimated DCSI scores increased from 0.84 (95% CI, 0.82-0.87) to 1.42 (95% CI, 1.36-1.47). Controlling for sociodemographic characteristics and medical comorbidities, SU disorders only (decrease in DCSI score, -0.09; 95% CI, -0.13 to -0.04; P < .001) or both MH and SU disorders (decrease in DCSI score, -0.13; 95% CI, -0.16 to -0.09; P < .001), but not MH disorders only, were associated with lower DCSI scores at the time of the onset of diabetes compared with no MH or SU disorders. More than 90% of patients with MH or SU disorders had primary care visits before diabetes was newly diagnosed, compared with approximately 58% of patients without MH or SU disorders. Patients who had primary care visits before the onset of diabetes had lower baseline DCSI scores, compared with patients who did not have primary care visits (decrease in DCSI score, -0.41 [95% CI, -0.43 to -0.39] for 1-2 visits, -0.50 [95% CI, -0.52 to -0.48] for 3-4 visits, -0.39 [95% CI, -0.41 to -0.37] for 5-8 visits, and -0.15 [95% CI, -0.17 to -0.12] for ≥9 visits; P < .001 for all). Patients with MH or SU disorders had lower overall, but more rapidly progressing, mean DCSI scores through year 7 after the onset of diabetes (MH disorder only, 0.006 [95% CI, 0.005-0.008], P < .001; SU disorder only, 0.005 [95% CI, 0.001-0.008], P = .004; or both MH and SU disorders, 0.008 [95% CI, 0.006-0.011], P < .001), compared with patients without MH or SU disorders. Conclusions and Relevance: Access to and engagement in integrated health care may be associated with modest, albeit impermanent, long-term health benefits for patients with MH and/or SU disorders with newly diagnosed diabetes.

Improved Healing of Diabetic Foot Ulcer upon Oxygenation Therapeutics through Oxygen-Loading Nanoperfluorocarbon Triggered by Radial Extracorporeal Shock Wave.

Diabetic foot ulcers (DFUs), the most serious complication of diabetes mellitus, can induce high morbidity, the need to amputate lower extremities, and even death. Although many adjunctive strategies have been applied for the treatment of DFUs, the low treatment efficiency, potential side effects, and high cost are still huge challenges. Recently, nanomaterial-based drug delivery systems (NDDSs) have achieved targeted drug delivery and controlled drug release, offering great promises in various therapeutics for diverse disorders. Additionally, the radial extracorporeal shock wave (rESW) has been shown to function as a robust trigger source for the NDDS to release its contents, as the rESW harbors a potent capability in generating pressure waves and in creating the cavitation effect. Here, we explored the performance of oxygen-loaded nanoperfluorocarbon (Nano-PFC) combined with the rESW as a treatment for DFUs. Prior to in vivo assessment, we first demonstrated the high oxygen affinity in vitro and great biocompatibility of Nano-PFC. Moreover, the rESW-responsive oxygen release behavior from oxygen-saturated Nano-PFC was also successfully verified in vitro and in vivo. Importantly, the wound healing of DFUs was significantly accelerated due to improved blood microcirculation, which was a result of rESW therapy (rESWT), and the targeted release of oxygen into the wound from oxygen-loaded Nano-PFC, which was triggered by the rESW. Collectively, the oxygen-saturated Nano-PFC and rESW provide a completely new approach to treat DFUs, and this study highlights the advantages of combining nanotechnology with rESW in therapeutics.

An Experimental Study to Evaluate the Protective Effects of Solanum lycopersicum Seed Essential Oil on Diabetes-Induced Testicular Injuries.

Background and Objectives: Diabetes is a chronic metabolic disorder that can effectively influences male reproductive performance. The present study was conducted to investigate the protective effects of Solanum lycopersicum essential oil (SL) on diabetes-induced testicular injuries. Materials and Methods: Adult male rats were randomly allocated into five groups (n = 8 in each group). 1: control; 2: diabetic; 3: diabetic + 30 mg/kg of SL essential oil; 4: diabetic + 90 mg/kg of SL essential oil; 5: diabetic + 270 mg/kg of SL essential oil extract. Diabetes was induced by a single dose of streptozotocin (55 mg/kg) intraperitoneally. Testicular changes were assessed quantitatively using stereological method followed by measuring antioxidant enzymes including catalase, superoxide dismutase, and glutathione peroxidase, and the serum testosterone level. Malondialdehyde (MDA) levels and Bcl-2expression were also evaluated in the tissue samples. Results: Diabetes resulted in significant deleterious changes in the structure of testicular tissue, suppressed antioxidant enzymes and testosterone levels, and increased lipid peroxidation. The expression of Bcl-2 was downregulated in diabetic testis and resulted in enhanced apoptosis. Following 8 weeks of treatment with SL essential oil, there were noticeable improvements in the structural changes of testis and the restoration of antioxidant defense and testosterone levels in testicular tissue, especially at higher doses. Conclusion: In conclusion, these findings reveal that the essential oil of Solanum lycopersicum has potent antioxidant properties and can attenuate the adverse effects of diabetes on male reproduction.