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Diabetes mellitus - Top 30 Publications

Postprandial renal haemodynamic effect of lixisenatide versus once-daily insulin glulisine in type 2 diabetes patients on insulin-glargine: an 8-week, randomised, open-label trial.

To determine whether lixisenatide, a prandial short-acting glucagon-like peptide receptor agonist (GLP-1RA), ameliorates postprandial glomerular hyperfiltration in type 2 diabetes mellitus (T2DM)-patients compared to insulin-glulisine (iGlu) .

Metformin use and the risk of colorectal adenoma: A systematic review and meta-analysis.

Although it is known that metformin can reduce risk of colorectal cancer, it is unclear whether it protects against colorectal adenoma.

A randomised, double-blind, trial of the safety and efficacy of omarigliptin (a once-weekly DPP-4 inhibitor) in subjects with type 2 diabetes and renal impairment.

To assess the safety and efficacy of omarigliptin in subjects with type 2 diabetes mellitus (T2DM) and chronic renal impairment (RI).

The LXR ligand T0901317 acutely inhibits insulin secretion by affecting mitochondrial metabolism.

The role of liver X receptor (LXR) in pancreatic beta-cell physiology and pathophysiology is still unclear. It has been postulated that chronic LXR activation in beta-cells induces lipotoxicity, a key step in the development of beta-cell dysfunction which accompanies type-2 diabetes mellitus. In most of these studies, the LXR ligand T0901317 has been administered chronically in the µmolar range to study the significance of LXR activation.In the present study, we have evaluated acute effects of T0901317 on stimulus-secretion coupling of beta-cells. We found that 10 µM T0901317 completely suppressed oscillations of the cytosolic Ca2+ concentration induced by 15 mM glucose. Obviously, this effect was due to inhibition of mitochondrial metabolism. T0901317 markedly depolarised the mitochondrial membrane potential, thus inhibiting ATP production and reducing the cytosolic ATP concentration. This led in turn to a huge increase in KATP current and hyperpolarization of the cell membrane potential. Eventually, T0901317 inhibited glucose-induced insulin secretion. These effects were rapid in on-set and not compatible with the activation of a nuclear receptor. In vivo, T0901317 acutely increased the blood glucose concentration after i.p.

Incidence of diabetic ketoacidosis among patients with type 2 diabetes mellitus treated with SGLT2 inhibitors and other antihyperglycemic agents.

To estimate and compare incidence of diabetes ketoacidosis (DKA) among patients with type 2 diabetes who are newly treated with SGLT2 inhibitors (SGLT2i) versus non-SGLT2i antihyperglycemic agents (AHAs) in actual clinical practice.

Diabetes status modifies the association between carotid intima-media thickness and incident heart failure: The Atherosclerosis Risk in Communities study.

Increasing carotid intima-media thickness (CIMT) is associated with incident heart failure (HF). We investigated whether this association differs by diabetes status.

A Motivational Interviewing Intervention by Pharmacy Students to Improve Medication Adherence.

Diabetes mellitus (DM) patients with comorbid hypertension (HTN) are at a higher risk of developing microvascular and macrovascular DM complications. Through guideline-driven recommendations, angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) are highly recommended for these patients. Unfortunately, medication adherence to these products, though crucial to achieving therapeutic benefit, is frequently suboptimal. Motivational interviewing (MI) is a patient-centered collaborative communication style that is used to strengthen internal motivation for change that may prove effective in enhancing adherence.

Effect of a Pharmacist-Led Program on Improving Outcomes in Patients with Type 2 Diabetes Mellitus from Northern Cyprus: A Randomized Controlled Trial.

The management of type 2 diabetes mellitus is complex, requiring continuous medical care by health care professionals and considerable self-care efforts by patients. Pharmacist-led care programs have been shown to help patients with diabetes succeed in achieving treatment goals and improving outcomes. Pharmacist-led care is a new health care concept in Northern Cyprus.

Retrograde intramedullary nail fixation for Charcot neuroarthropathy.

Charcot arthropathy is defined as an articular degenerative, chronic, progressive disease that affects one or more peripheral joints, develops as a result of a failure in the normal sensory perception (pain and proprioception) in the innervation of joints located in the foot and ankle, is characterized by destructive bone lesions without the presence of infection. Neuropathy is directly associated with diabetes mellitus type 1 and 2. Surgery is indicated when there is severe involvement of soft tissue, foot joints are unstable, at the presence of chronic or recurrent ulcers or when the foot and ankle can not fit to a normal shoe, and had limitation to perform activities of daily living.

Clinical presentation and management of stable coronary artery disease in Austria.

Cardiovascular disease is the main cause of death in Austria. However, no systematic information exists regarding characteristics and treatments of contemporary patients with stable coronary artery disease (CAD) in Austria. We assembled two retrospective physicians' databases to describe demographics, clinical profiles, and therapeutic strategies in patients with stable CAD. In addition, we compared patient profiles of secondary care internists and hospital-based cardiologists with those of general practitioners in a primary care setting outside of hospital.

Combined lipidomic and proteomic analysis of isolated human islets exposed to palmitate reveals time-dependent changes in insulin secretion and lipid metabolism.

Studies on the pathophysiology of type 2 diabetes mellitus (T2DM) have linked the accumulation of lipid metabolites to the development of beta-cell dysfunction and impaired insulin secretion. In most in vitro models of T2DM, rodent islets or beta-cell lines are used and typically focus is on specific cellular pathways or organs. Our aim was to, firstly, develop a combined lipidomics and proteomics approach for lipotoxicity in isolated human islets and, secondly, investigate if the approach could delineate novel and/ or confirm reported mechanisms of lipotoxicity. To this end isolated human pancreatic islets, exposed to chronically elevated palmitate concentrations for 0, 2 and 7 days, were functionally characterized and their levels of multiple targeted lipid and untargeted protein species determined. Glucose-stimulated insulin secretion from the islets increased on day 2 and decreased on day 7. At day 7 islet insulin content decreased and the proinsulin to insulin content ratio doubled. Amounts of cholesterol, stearic acid, C16 dihydroceramide and C24:1 sphingomyelin, obtained from the lipidomic screen, increased time-dependently in the palmitate-exposed islets. The proteomic screen identified matching changes in proteins involved in lipid biosynthesis indicating up-regulated cholesterol and lipid biosynthesis in the islets. Furthermore, proteins associated with immature secretory granules were decreased when palmitate exposure time was increased despite their high affinity for cholesterol. Proteins associated with mature secretory granules remained unchanged. Pathway analysis based on the protein and lipid expression profiles implicated autocrine effects of insulin in lipotoxicity. Taken together the study demonstrates that combining different omics approaches has potential in mapping of multiple simultaneous cellular events. However, it also shows that challenges exist for effectively combining lipidomics and proteomics in primary cells. Our findings provide insight into how saturated fatty acids contribute to islet cell dysfunction by affecting the granule maturation process and confirmation in human islets of some previous findings from rodent islet and cell-line studies.

Thymoquinone Defeats Diabetes-Induced Testicular Damage in Rats Targeting Antioxidant, Inflammatory and Aromatase Expression.

Antioxidants have valuable effects on the process of spermatogenesis, particularly with diabetes mellitus (DM). Therefore, the present study investigated the impact and the intracellular mechanisms by which thymoquinone (TQ) works against diabetes-induced testicular deteriorations in rats. Wistar male rats (n = 60) were randomly allocated into four groups; Control, Diabetic (streptozotocin (STZ)-treated rats where diabetes was induced by intraperitoneal injection of STZ, 65 mg/kg), Diabetic + TQ (diabetic rats treated with TQ (50 mg/kg) orally once daily), and TQ (non-diabetic rats treated with TQ) for 12 weeks. Results revealed that TQ significantly improved the sperm parameters with a reduction in nitric oxide (NO) and malondialdehyde (MDA) levels in testicular tissue. Also, it increased testicular reduced glutathione (GSH) levels and superoxide dismutase (SOD) activity. Interestingly, TQ induced downregulation of testicular inducible nitric oxide synthase (iNOS) and nuclear factor kappa-B (NF-κB) and significantly upregulated the aromatase protein expression levels in testicles in comparison with the diabetic rats. In conclusion, TQ treatment exerted a protective effect against reproductive dysfunction induced by diabetes not only through its powerful antioxidant and hypoglycemic effects but also through its downregulation of testicular iNOS and NF-κB along with upregulation of aromatase expression levels in diabetic rats.

Factors Associated with Decreased Lean Tissue Index in Patients with Chronic Kidney Disease.

Muscle wasting is common and is associated with increased morbidity and mortality in patients with chronic kidney disease (CKD). However, factors associated with decreased muscle mass in CKD patients are seldom reported. We performed a cross-sectional study of 326 patients (age 65.8 ± 13.3 years) with stage 3-5 CKD who were not yet on dialysis. Muscle mass was determined using the Body Composition Monitor (BCM), a multifrequency bioimpedance spectroscopy device, and was expressed as the lean tissue index (LTI, lean tissue mass/height²). An LTI of less than 10% of the normal value (low LTI) indicates muscle wasting. Patients with low LTI (n = 40) tended to be diabetic, had significantly higher fat tissue index, urine protein creatinine ratio, and interleukin-6 and tumor necrosis factor-α levels, but had significantly lower serum albumin and hemoglobin levels compared with those with normal LTI. In multivariate linear regression analysis, age, sex, cardiovascular disease, and interleukin-6 were independently associated with LTI. Additionally, diabetes mellitus remained an independent predictor of muscle wasting according to low LTI by multivariate logistic regression analysis. We conclude that LTI has important clinical correlations. Determination of LTI may aid in clinical assessment by helping to identify muscle wasting among patients with stage 3-5 CKD.

Once-weekly dipeptidyl peptidase-4 inhibitors for type 2 diabetes: a systematic review and meta-analysis.

To assess the efficacy and safety of omarigliptin and trelagliptin, novel dipeptidyl peptidase-4 inhibitors administered once-weekly (DPP-4i QW).

Intrinsic mesenchymal stem cell dysfunction in diabetes mellitus: Implications for autologous cell therapy.

Mesenchymal stem cells derived from bone marrow (BM-MSCs) have multi-functional properties that have made them a promising therapeutic agent for many regenerative, anti-inflammatory, and auto-immune applications. Under chronic pathological conditions, however, BM-MSCs can become functionally compromised due to long term exposure to changes in the systemic and localized stem cell niche micro-environments. In addition to the fact that functionally compromised BM-MSCs may be therapeutically ineffective, the impairment of BM-MSCs is potentially a contributing factor to disease progression and the development of co-morbidities. For the purpose of this review, MSC-based therapies for the treatment of non-healing wounds in diabetic patients will be used as example to demonstrate the effect that the diabetic host environment has on the regenerative capacity of endogenous BM-MSCs. This review will also discuss the mechanism by which the pathogenesis of diabetes mellitus leads to intrinsic dysfunction of the bone marrow stem cell niche that ultimately results in MSC failure and will highlight potential strategies for counteracting the functional decline of BM-MSCs.

Prevalence and Clinical Significance of Diabetes in Asian Versus White Patients With Heart Failure.

The study sought to compare the prevalence, clinical correlates and prognostic impact of diabetes in Southeast Asian versus white patients with heart failure (HF) with preserved or reduced ejection fraction.

A New Treatment Strategy for Parkinson's Disease Through the Gut-Brain Axis: The Glucagon-like Peptide-1 Receptor Pathway.

Molecular communications in the gut-brain axis, between the central nervous system and the gastrointestinal tract, arecritical for maintaining healthy brain function particularly in aging. Epidemiological analyses indicate type 2 diabetes mellitus (T2DM) is a risk factor for neurodegenerative disorders, including Alzheimer's disease (AD) and Parkinson's diseases (PD) for which aging shows a major correlative association. Common pathophysiological features exist between T2DM, AD and PD, including oxidative stress, inflammation, insulin resistance, abnormal protein processing and cognitive decline, and suggest that effective drugs for T2DM that positively impact the gut-brain axis could provide an effective treatment option for neurodegenerative diseases. Glucagon-like peptide-1 (GLP-1)-based anti-diabetic drugs have drawn particular attention as an effectual new strategy to not only regulate blood glucose but also to decrease body weight by reducing appetite, which implies that GLP-1 could affect the gut-brain axis in normal and pathological conditions. The neurotrophic and neuroprotective effects of GLP-1 receptor (R) stimulation have been characterized in numerous in vitro and in vivo preclinical studies using GLP-1R agonists and dipeptidyl peptidase 4 inhibitors. Recently, the first open label clinical study of exenatide, a long acting GLP-1 agonist, in the treatment of PD showed long-lasting improvements in motor and cognitive function. Several double blind clinical trials of GLP-1R agonists including exenatide in PD and other neurodegenerative disease are already underway or are about to be initiated. Herein, we review the physiological role of the GLP-1R pathway in the gut-brain axis and the therapeutic strategy of GLP-1R stimulation for the treatment of neurodegenerative diseases focused on PD, for which age is the major risk factor.

Centella asiatica enhances hepatic antioxidant status and regulates hepatic inflammatory cytokines in type 2 diabetic rats.

Neutralizing the over-activation of oxidative stress and inflammation remains an important goal in the management of type 2 diabetes mellitus (T2DM). Centella asiatica (L.) Urban (Apiaceae) (CA) has been used in traditional folklore in Africa and Asia to treat various ailments including diabetes.

Response: Efficacy of Moderate Intensity Statins in the Treatment of Dyslipidemia in Korean Patients with Type 2 Diabetes Mellitus (Diabetes Metab J 2017;41:23-30).

Letter: Efficacy of Moderate Intensity Statins in the Treatment of Dyslipidemia in Korean Patients with Type 2 Diabetes Mellitus (Diabetes Metab J 2017;41:23-30).

Addition of Ipragliflozin to Metformin Treatment in Korean Patients with Type 2 Diabetes Mellitus: Subgroup Analysis of a Phase 3 Trial.

This is a subgroup analysis of Korean patients from a phase 3 clinical trial investigating the efficacy and safety of ipragliflozin in patients with type 2 diabetes mellitus inadequately controlled with metformin.

Lipid Abnormalities in Type 2 Diabetes Mellitus Patients with Overt Nephropathy.

Diabetic nephropathy is a major complication of diabetes and an established risk factor for cardiovascular events. Lipid abnormalities occur in patients with diabetic nephropathy, which further increase their risk for cardiovascular events. We compared the degree of dyslipidemia among type 2 diabetes mellitus (T2DM) subjects with and without nephropathy and analyzed the factors associated with nephropathy among them.

Diabetes Camp as Continuing Education for Diabetes Self-Management in Middle-Aged and Elderly People with Type 2 Diabetes Mellitus.

Despite the established benefits of diabetes camps for the continuing education of children with type 1 diabetes mellitus, little is known about the long-term metabolic benefits of diabetes camps for middle-aged and elderly people with type 2 diabetes mellitus (T2DM), especially in terms of glycosylated hemoglobin (HbA1c) variability.

Role of NO/VASP Signaling Pathway against Obesity-Related Inflammation and Insulin Resistance.

Obesity has quickly become a worldwide pandemic, causing major adverse health outcomes such as dyslipidemia, type 2 diabetes mellitus, cardiovascular disease and cancers. Obesity-induced insulin resistance is the key for developing these metabolic disorders, and investigation to understand the molecular mechanisms involved has been vibrant for the past few decades. Of these, low-grade chronic inflammation is suggested as a critical concept in the development of obesity-induced insulin resistance, and the anti-inflammatory effect of nitric oxide (NO) signaling has been reported to be linked to improvement of insulin resistance in multiple organs involved in glucose metabolism. Recently, a body of evidence suggested that vasodilatory-stimulated phosphoprotein (VASP), a downstream mediator of NO signaling plays a crucial role in the anti-inflammatory effect and improvement of peripheral insulin resistance. These preclinical studies suggest that NO/VASP signaling could be an ideal therapeutic target in the treatment of obesity-related metabolic dysfunction. In this review, we introduce studies that investigated the protective role of NO/VASP signaling against obesity-related inflammation and insulin resistance in various tissues.

A Clinical Practice Guideline to Guide a System Approach to Diabetes Care in Hong Kong.

The Hospital Authority of Hong Kong is a statutory body that manages all the public medical care institutions in Hong Kong. There are currently around 400,000 diabetic patients under its care at 17 hospitals (providing secondary care for 40%) and 73 General Outpatient Clinics (providing primary care for 60%). The patient population has been growing at 6% to 8% per year over the past 5 years, estimated to include over 95% of all diagnosed patients in Hong Kong. In order to provide equitable and a minimal level of care within resources and local system factors constraints, a Clinical Practice Guideline on the management of type 2 diabetes mellitus was drawn in 2013 to guide a system approach to providing diabetes care. There is an algorithm for the use of various hypoglycemic agents. An organizational drug formulary governs that less expansive options have to be used first. A number of clinical care and patient empowerment programs have been set up to support structured and systematic diabetes care. With such a system approach, there have been overall improvements in diabetes care with the percentage of patients with glycosylated hemoglobin <7% rising from 40% in 2010 to 52% in 2015.

Comment on the New Indian Injection Technique Recommendations: Critical Appraisal of the Real-World Implementation of the Current Guidelines.

With an eye on the sequence of two Indian papers concurrently published in Diabetes Therapy, this paper analyzes skin differences among races and points to a lack of organized structured education sessions as the main cause of the high prevalence of lipodystrophy (LD) and consequent poor metabolic control. Only half of all insulin-treated patients reach their therapeutic targets worldwide. The factors involved in this are manifold, including the choice of overlong and repeatedly reused needles, as well as a failure to systematically rotate injection sites, all of which lead to skin LD. Regularly issued guidelines and expert recommendations provide suggestions about how to correct poor injection techniques, but LD still occurs at a high rate and is associated with poor metabolic control, a high risk of complications, frequent severe hypoglycemic episodes, and huge health and social costs. Poor knowledge of subcutaneous tissue anatomy and the physiological response to insulin injection by both health care personnel and patients may contribute to this problem. Moreover, differences in body structure among the races present in our multiethnic societies must be taken into account when choosing needle length and shooting technique in order to avoid accidental intramuscular injections.

Prevalence of fibromyalgia in general population and patients, a systematic review and meta-analysis.

This study aims to estimate the reliable prevalence of fibromyalgia using meta-analysis method. Available databanks were searched using appropriate keywords. According to the heterogeneity between the results (indicated by Cochrane and I square indices), random- or fixed-effects model was applied to combine the point prevalences. Meta-regression models were used to assess the suspected factors in the heterogeneity. In 65 selected papers, 81 evidences regarding prevalence of fibromyalgia among 3,609,810 subjects from general population and specific groups were investigated. The total prevalences (95% confidence intervals) of fibromyalgia among general population, women, men, patients referring to rheumatology and internal departments, patients with Irritable bowel syndrome (IBS), hemodialysis patients and those with type 2 diabetes mellitus were estimated as of 1.78% (1.65, 1.92), 3.98% (2.80, 5.20), 0.01% (-0.04, 0.06), 15.2% (13.6, 16.90), 12.9% (12.70, 13.10), 6.30% (4.60, 7.90) and 14.80% (11.10, 18.40), respectively. In addition, prevalence of fibromyalgia in specified groups varied from 3.90% in hemodialysis patients to 80% in patients suffering from Behcet syndrome. This meta-analysis showed that prevalence of fibromyalgia in general population was significantly lower than that in populations with some diseases.

SGLT-2 Inhibition with Dapagliflozin Reduces the Activation of the Nlrp3/ASC Inflammasome and Attenuates the Development of Diabetic Cardiomyopathy in Mice with Type 2 Diabetes. Further Augmentation of the Effects with Saxagliptin, a DPP4 Inhibitor.

We assessed whether (1) dapagliflozin (Dapa, an SGLT2-inhibitor) attenuates the deterioration of heart function Nlrp3 and inflammasome activation in diabetic mice. (2) The effects can be augmented with saxagliptin (Saxa), a DDP4-inhibitor. (3) Dapa effect is possibly SGLT2-independent on cardiofibroblasts in vitro.

Clinical and microbiological features associated with group B Streptococcus bone and joint infections, France 2004-2014.

This study describes the clinical and microbiological features associated with group B Streptococcus (GBS) bone and joint infections (BJIs). It was a retrospective analysis of adult cases of GBS BJIs reported to the French National Reference Center for Streptococci from January 2004 to December 2014. Clinical data and GBS molecular characteristics are reported. Strains were collected from 163 patients. The most frequent comorbidities were: solid organ cancer (n = 21, 21%) and diabetes mellitus (n = 20, 20%). The main infection sites were knee (47/155 = 30%) and hip (43/155 = 27%), and occurred on orthopedic devices in 71/148 cases (48%). CPS III (n = 47, 29%), Ia (n = 26, 16%) and V (n = 40, 25%) were predominant. Resistance to erythromycin, clindamycin and tetracycline was detected in 55/163 (34%), 35/163 (21%) and 132/163 (81%) strains, respectively. The most frequent sequence types were ST-1 (n = 21, 25%), ST-17 (n = 17, 20%) and ST-23 (n = 11, 13%). The rate of resistance to erythromycin was 0% for ST-17 strains, 52% (n = 11) for ST-1 and 44% (n = 7) for ST-23 (p < 0.001). GBS bone and joint infections predominantly occur in patients aged >50 years and/or with comorbidities such as cancer and diabetes mellitus. CPS type distribution and MLST are very similar to that of other adult GBS invasive infections.

Brain changes in overweight/obese and normal-weight adults with type 2 diabetes mellitus.

Overweight and obesity may significantly worsen glycaemic and metabolic control in type 2 diabetes. However, little is known about the effects of overweight and obesity on the brains of people with type 2 diabetes. Here, we investigate whether the presence of overweight or obesity influences the brain and cognitive functions during early stage type 2 diabetes.