Exploring potent aldose reductase inhibitors for anti-diabetic (anti-hyperglycemic) therapy: integrating structure-based drug design, and MMGBSA approaches.

Aldose reductase (AR) is an important target in the development of therapeutics against hyper-glycemia-induced health complications such as retinopathy, etc. In this study, we employed a combination of structure-based drug design, molecular simulation, and free energy calculation approaches to identify potential hit molecules against anti-diabetic (anti-hyperglycemic)-induced health complications. The 3D structure of aldoreductase was screened for multiple compound libraries (1,00,000 compounds) and identified as ZINC35671852, ZINC78774792 from the ZINC database, Diamino-di nitro-methyl dioctyl phthalate, and Penta-o-galloyl-glucose from the South African natural compounds database, and Bisindolylmethane thiosemi-carbazides and Bisindolylme-thane-hydrazone from the Inhouse database for this study. The mode of binding interactions of the selected compounds later predicted their aldose reductase inhibitory potential. These com-pounds interact with the key active site residues through hydrogen bonds, salt bridges, and π-π interactions. The structural dynamics and binding free energy results further revealed that these compounds possess stable dynamics with excellent binding free energy scores. The structures of the lead inhibitors can serve as templates for developing novel inhibitors, and in vitro testing to confirm their anti-diabetic potential is warranted. The current study is the first to design small molecule inhibitors for the aldoreductase protein that can be used in the development of therapeutic agents to treat diabetes.

Development of a tailored intervention targeting sedentary behavior and physical activity in people with stroke and diabetes: A qualitative study using a co-creation framework.

Purpose: Type 2 diabetes and sedentary behavior pose serious health risks in stroke survivors. Using a co-creation framework, this study aimed to develop an intervention in collaboration with stroke survivors with type 2 diabetes, relatives, and cross-sectoral health care professionals to reduce sedentary behavior and increase physical activity. Materials and methods: This qualitative explorative study used a co-creation framework consisting of a workshop and focus group interviews with stroke survivors with type 2 diabetes (n = 3), relative (n = 1), and health care professionals (n = 10) to develop the intervention. A content analysis was used to analyze data. Results: The developed "Everyday Life is Rehabilitation" (ELiR) intervention consisted of a tailored 12-week home-based behavior change intervention with two consultations of action planning, goal setting, motivational interviewing, and fatigue management including education on sedentary behavior, physical activity, and fatigue. The intervention has a minimalistic setup using a double-page paper "Everyday Life is Rehabilitation" (ELiR) instrument making it implementable and tangible. Conclusions: In this study, a theoretical framework was used to develop a tailored 12-week home-based behavior change intervention. Strategies to reduce sedentary behavior and increase physical activity through activities of daily living along with fatigue management in stroke survivors with type 2 diabetes were identified.

Oat ß-glucan ameliorates diabetes in high fat diet and streptozotocin-induced mice by regulating metabolites.

Oats are widely distributed worldwide and oat ß-glucan has positive effects on human health. Particularly, oat ß-glucan is reported to be beneficial in the management of type 2 diabetes. The aim of the present study is to investigate the effects of oat ß-glucan and its possible underlying mechanisms on diabetes in type 2 diabetic mice that was induced by streptozotocin/high-fat diet (STZ/HFD). The data indicated that oat ß-glucan significantly reduced the fasting blood glucose, improved glucose tolerance, and insulin sensitivity. The results further showed that oat ß-glucan remarkably decreased the levels of total cholesterol (TCHO), total triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and free fatty acids. Moreover, oat ß-glucan remarkably increased the hepatic glycogen content, but largely decreased the levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in STZ/HFD-induced diabetic mice. Histological analysis showed that oat ß-glucan alleviated visceral lesions. Finally, the metabolomic analysis indicated that the metabolic profile was remarkably changed after oat ß-glucan intervention in diabetic mice. There were 88 and 106 differential metabolites screened as biomarkers in negative ion mode (NEG) and positive ion mode (POS) after oat ß-glucan treatment, respectively. In addition, oat ß-glucan significantly affected the serum metabolites of amino acids, organic acids and bile acids. Collectively, the current study elucidates oat ß-glucan displays an effective nutritional intervention in diabetes.

Importance of Heparan Sulfate Proteoglycans in Pancreatic Islets and ß-Cells.

ß-cells in the islets of Langerhans of the pancreas secrete insulin in response to the glucose concentration in the blood. When these pancreatic ß-cells are damaged, diabetes develops through glucose intolerance caused by insufficient insulin secretion. High molecular weight polysaccharides, such as heparin and heparan sulfate (HS) proteoglycans, and HS-degrading enzymes, such as heparinase, participate in the protection, maintenance, and enhancement of the functions of pancreatic islets and ß-cells, and the demand for studies on glycobiology within the field of diabetes research has increased. This review introduces the roles of complex glycoconjugates containing high molecular weight polysaccharides and their degrading enzymes in pancreatic islets and ß-cells, including those obtained in studies conducted by us earlier. In addition, from the perspective of glycobiology, this study proposes the possibility of application to diabetes medicine.

Pilates training reduces blood pressure in older women with type 2 diabetes: A randomized controlled trial.

INTRODUCTION: The study investigated the effect of 12 weeks of pilates training on the hemodynamic responses of older women with type-2 diabetes (T2D). METHODS: 22 individuals with T2D were randomly allocated into two groups: CONTROL (n = 11; 67.5 ± 6.3 years; 154.7 ± 6.1 cm; 73.5 ± 6.1 kg; calorie intake: 1487.5 ± 360.6 kcal/day) and PILATES (n = 11; 65.5 ± 5.5 years; 155.0 ± 4.5 cm; 66.2 ± 5.4 kg; calorie intake: 1289.3 ± 385.0 kcal/day). The PILATES group executed a 12-week PILATES training program at moderate intensity, 3x/week with each session lasting 60-min. Systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), and postprandial blood glucose were assessed at four timepoints: i) baseline; ii) 4th week; iii) 8th week; and iv) 12th week (s) of intervention. Two-way ANOVA for repeated measures and the Pearson's correlation coefficient were adopted. The alpha level was set at 0.05. RESULTS: A time∗group interaction effect was found for SBP (F = 4.206; η2 = 0.17; p = 0.02) and DBP (F = 2.624; η2 = 0.12; p = 0.05) with significant reductions (mmHg) in the 4ths and 8ths in the PILATES (PILATES SBP baseline: 134.9 ± 27.6; 4ths: 112.4 ± 15.7; 8ths: 115.8 ± 18.3; 12ths: 124.3 ± 19.1 vs. CONTROL SBP baseline: 126.5 ± 15.7; 4ths: 126.3 ± 16.2; 8ths: 124.5 ± 13.1; 12ths: 126.3 ± 21.4 | PILATES DBP baseline: 72.9 ± 11.3; 4ths: 65.1 ± 12.2; 8ths: 65.8 ± 12.2; 12ths: 67.6 ± 7.5 vs. CONTROL DBP baseline: 74.6 ± 12.0; 4ths: 73.9 ± 11.5; 8ths: 75.3 ± 11.9; 12ths: 74.5 ± 9.2). CONCLUSION: Four and eight weeks of PILATES training promotes reduction in the SBP and DBP of older women with T2D. The exercises performed in this study were mainly body weight exercises and required a few auxiliary materials, which turns this method of training accessible.

Disease-specific quality of life in patients with diabetic neuropathy.

OBJECTIVES: To compare health-related quality of life (HRQoL) among patients with diabetes mellitus (DM) and diabetic neuropathy (DN) (D+N) with patients with DM without DN (D-DN) and healthy participants. To evaluate factors associated with poor HRQoL in patients with DN. METHODS: This study included 306 participants residing in Bisha, Saudi Arabia. Patients with DM were screened for DN using the Michigan Neuropathy Screening Instrument. Neuropathy severity, disability and HRQoL were determined using the Neuropathy Severity Scale (NSS), the Neuropathy Disability Score (NDS), and the Norfolk Quality of Life-Diabetic Neuropathy (QOL-DN) tool, respectively. Nerve conduction studies (NCSs) were also performed. RESULTS: The D+DN group had poorer overall and domain HRQoL scores compared to the D-DN group (p<0.001). There was a strong correlation between overall HRQoL score and both NDS and NSS scores in the D+DN group (ρ= -0.71 and p<0.0001; ρ= -0.81 and p<0.0001, respectively). There was also a significant difference in all mean HRQoL domain scores between D+DN participants with normal and abnormal NCS. Physical inactivity (p=0.043), duration of DM (p<0.0001), abnormal NCS, NSS (p<0.0001), and NDS (p<0.0001) predicted HRQoL in the D+DN group. CONCLUSION: D+DN participants had a worse HRQoL compared with D-DN and healthy counterparts. NDS, NNS, physical inactivity, abnormal NCS, and duration of DM independently predicted poor HRQoL in D+DN participants.

Lower / upper extremity F-wave ratio for detecting early diabetic neuropathy.

BACKGROUND AND PURPOSE: Results of conventional nerve conduction studies may be within normal limits in early diabetic neuropathy. Previous studies demonstrated that F-wave latency should be used to detect this early neuropathic process. The aim of this study is to evaluate the sensitivity of lower/upper extremity F latency ratios in detecting the early neuropathy in patients with diabetic neuropathic pain. METHODS: 44 patients with diabetic neuropathic pain (DNP) and 44 control subjects whose both conventional nerve conduction studies and F-wave latencies were within normal limits were included to the study. We compared the nerve conduction parameters and lower/upper extremity (tibial/ulnar) F latency ratios of the groups. RESULTS: Tibial F latency was significantly prolonged and tibial/ulnar F latency ratio was significantly higher in DNP group. Our results support that F-waves are useful for detecting early diabetic neuropathy and suggest that comparison with a control group will demonstrate a difference even when the individuals' F-wave latencies are within the normal limits. The difference was significant for tibial but not for ulnar F latency values supporting the length dependent involvement. The tibial/ ulnar F-wave latency ratio was significantly higher in the DNP group, suggesting that it might also be useful to detect early neuropathy and to demonstrate that the underlying process was predominant in lower extremity. CONCLUSION: Further studies may provide additional information about the utility of this ratio for detecting early neuropathy even when F-wave latencies are within normal limits.

A Phase I Randomized, Double-blind, Placebo-controlled Study on Efficacy and Safety Profile of a Sublingually Administered Cannabidiol /Delta 9-tetrahydrocannabidiol (10: 1) Regimen in Diabetes Type 2 Patients.

The current study aimed to evaluate the safety profile and efficacy of a cannabis-based sublingual spray, CBDEX10® (containing 100 µg cannabidiol and 10 µg Δ9-tetrahydrocannabinol per puff; CBD/Δ9-THC 10:1), in improving lipid profile and glycemic state of the diabetic patients. Fifty diabetic patients were randomly allocated to the treatment (n = 25; receiving two puffs of CBDEX10® twice daily) or the control groups (n = 25; receiving two puffs of placebo). The primary endpoint of the study was to evaluate the efficacy of the CBDEX10® adjunctive therapy in improving the lipid profile and glycemic state of diabetic patients; the secondary endpoint was to assess the safety profile and tolerability of the spray. A statistically significant decline in total cholesterol [estimated treatment difference (ETD) = -19.73 mg/dL; P < 0.05], triglyceride (ETD = -27.84 mg/dL; P < 0.01), LDL-C (ETD = -5.37 mg/dL; P < 0.01), FBS (ETD = -12 mg/dL; P < 0.01), Hb A1C (ETD = -0.21 mg/dL; P < 0.01) and insulin secretion (ETD = -5.21 mIU/L; P < 0.01) was observable in the patients treated with CBDEX10® at the end of the 8-week treatment period. Regarding safety, the mentioned adjunctive regimen was well, and there were no serious or severe adverse effects. Overall, CBDEX1® sublingual spray could be a new therapeutic agent for lipid and glycemic control in diabetic patients.

A Gravidade da Doença Afeta os Parâmetros de Repolarização Ventricular em Pacientes com COVID-19 / Disease Severity Affects Ventricular Repolarization Parameters in Patients With COVID-19

Resumo Fundamento: Não há estudos avaliando o intervalo Tpico-Tfim (Tpe), a relação Tpe/QT e a relação Tpe/QTc para avaliar arritmias cardíacas em pacientes com COVID-19. Objetivo: Visamos investigar se há alterações nos intervalos QT, QTc e Tpe e nas relações Tpe/QT e Tpe/QTc em pacientes com COVID-19. Métodos: O estudo incluiu 90 pacientes com infecção por COVID-19 e 30 controles saudáveis pareados por sexo e idade. Foram aferidos os intervalos QT, QTc e Tpe e as relações Tpe/QT e Tpe/QTc. Os participantes incluídos no estudo foram divididos nos seguintes 4 grupos: controles saudáveis (grupo I), pacientes com COVID-19 sem pneumonia (grupo II), pacientes com COVID-19 e pneumonia leve (grupo III) e pacientes com COVID-19 e pneumonia grave (grupo IV). Significância estatística foi definida por valor p < 0,05. Resultados: Verificou-se que a frequência cardíaca basal, a presença de hipertensão e diabetes, a contagem de leucócitos, o nitrogênio ureico no sangue, a creatinina, o potássio, o aspartato aminotransferase, a alanina aminotransferase, o NT-proBNP, a proteína C reativa de alta sensibilidade, o dímero-D, a TncI-as, o intervalo Tpe, a relação Tpe/QT e a relação Tpe/QTc aumentaram do grupo I para o grupo IV e foram significativamente mais altos em todos os pacientes do grupo IV (p < 0,05). A pressão arterial sistólica, a hemoglobina e os níveis de cálcio eram menores no grupo IV e significativamente menores em comparação com os demais grupos (< 0,05). Os intervalos QT e QTc eram semelhantes entre grupos. Determinou-se que os níveis elevados de frequência cardíaca, cálcio, dímero-D, NT-proBNP e PCR-as eram significativamente relacionados a Tpe, Tpe/QT e Tpe/QTc. Conclusões: Em pacientes com COVID-19 e pneumonia grave, o intervalo Tpe, a relação Tpe/QT e a relação Tpe/QTc, que estão entre os parâmetros de repolarização ventricular, foram aumentados, sem prolongação dos intervalos QT e QTc. A partir deste estudo, não podemos definitivamente concluir que as alterações eletrocardiográficas observadas estão diretamente relacionadas à infecção por COVID-19 ou à inflamação, mas sim associadas a cenários graves de COVID-19, que podem envolver outras causas de inflamação e comorbidades.

Abstract Background: There is no study evaluating the Tpeak-Tend (Tpe) interval, Tpe/QT ratio, and Tpe/QTc ratio to assess cardiac arrhythmias in patients with COVID-19. Objective: We aimed to examine whether there is a change in QT, QTc, Tpe interval, Tpe/QT ratio, and Tpe/QTc ratio in patients with COVID-19. Methods: The study included 90 patients with COVID-19 infection and 30 age-and-sex-matched healthy controls. QT, QTc, Tpe interval, Tpe/QT ratio, and Tpe/QTc ratio were measured. The participants included in the study were divided into the following 4 groups: healthy controls (group I), patients with COVID-19 without pneumonia (group II), patients with COVID-19 and mild pneumonia (group III), and patients with COVID-19 and severe pneumonia (group IV). Statistical significance was set at p < 0.05. Results: It was found that baseline heart rate, presence of hypertension and diabetes, white blood cell count, blood urea nitrogen, creatinine, potassium, aspartate aminotransferase, alanine aminotransferase, NT-proBNP, high sensitive C reactive protein, D-dimer, hs-cTnI, Tpe, Tpe/QT, and Tpe/QTc increased from group I to group IV, and they were significantly higher in all patients in group IV (p < 0.05). Systolic-diastolic blood pressure, hemoglobin, and calcium levels were found to be lowest in group IV and significantly lower than in other groups (< 0.05). QT and QTc intervals were similar between groups. It was determined that increased heart rate, calcium, D-dimer, NT-proBNP and hs-CRP levels were significantly related to Tpe, Tpe/QT, and Tpe/QTc. Conclusions: In patients with COVID-19 and severe pneumonia, Tpe, Tpe/QT ratio, and Tpe/QTc ratio, which are among ventricular repolarization parameters, were found to be increased, without prolonged QT and QTc intervals. In this study, we cannot definitively conclude that the ECG changes observed are directly related to COVID-19 infection or inflammation, but rather associated with severe COVID-19 scenarios, which might involve other causes of inflammation and comorbidities. (Arq Bras Cardiol. 2020; 115(5):907-913)

Diabetic autonomic neuropathy of the gastrointestinal tract.

Diabetes is a metabolic disease leading to the development of numerous health complications. In developed countries, it is the main cause of blindness, end-stage renal disease, and non-traumatic amputation of the lower limbs. Neuropathy is the most common chronic complication of diabetes. A long-term course of a metabolically unbalanced disease causing damage to the autonomic nervous system of the digestive tract results in the development of many complications, such as intensification of gastro-oesophageal reflux disease, gastroparesis, chronic diarrhoea or faecal incontinence.

Clinical manifestations and associated disorders in children with celiac disease in southern Iran.

BACKGROUND: Celiac disease (CD) is an immune mediated inflammatory enteropathy, triggered by gluten exposure in HLA-DQ2 and/or -DQ8 genetics. The presentation of celiac disease in children is changing, with increase in non-classical symptoms. We aim to evaluate the clinical presentations of celiac disease amongst children, diagnosed with CD. METHODS: In this cross sectional study, we investigated the clinical features of 130 celiac patients at hospitals affiliated with Shiraz University of Medical Sciences. We used their hospital charts and conducted an interview with patients and their parents to find out demographic data, symptoms, laboratory, and histopathology findings for Marsh grading. RESULTS: Celiac disease was detected more amongst females (63.8%). We found that 5.4% of the patients had BMI more than 95th percentile. The most common GI symptoms were abdominal pain, flatulence and constipation. Also, the most common extra intestinal manifestation included bone pain, long term fatigue and anemia. Flatulence, chronic diarrhea, and paresthesia were observed more amongst male participants. The most common comorbidities were type 1 diabetes mellitus and hypothyroidism. CONCLUSION: The most common gastrointestinal symptoms amongst our patients were abdominal pain, flatulence and constipation. Furthermore, the most common extra intestinal manifestations included bone pain, long term fatigue and anemia. The most associated comorbidities with CD in our children were type 1 diabetes mellitus and hypothyroidism.

Evaluating glycaemic control in patients poorly controlled on oral antidiabetic drugs in real-world setting: Results from assessing the Appropriate Timing of Type 2 diAbetes INtensification (ATTAIN).

INTRODUCTION: Many patients with type 2 diabetes mellitus (DM) fail to achieve glycaemic control despite recommended treatment strategies to reduce glycated haemoglobin (HbA1c). This real-world retrospective cohort study compared HbA1c change and treatment patterns between those intensifying and not intensifying therapy with oral antidiabetic drugs (OADs). MATERIALS AND METHODS: Patients suboptimally controlled on OADs (>58 mmol/mol [>7.5%] or >64 mmol/mol [>8.0%] for high risk, index 1) were included from IQVIA Medical Research Data. Intensifiers within 12 months of index 1 were matched (1:1) to nonintensifiers. Primary outcomes were HbA1c change and proportion of participants achieving HbA1c targets 6 and 12 months post-index 2 (date of intensification [intensifiers] or pseudodate [nonintensifiers]). Therapy adherence was also assessed. RESULTS: A total of 10 832 participants (5539 intensifiers and 5293 nonintensifiers) were included. Mean HbA1c decrease from baseline to 6 months was -1.13% (intensifiers) vs -0.75% (nonintensifiers), with no substantial further change at 12 months. Cox proportional hazards (PH) analysis suggested a nearly 20% greater chance of target achievement at 6 months for intensifiers vs nonintensifiers (hazard ratio [HR]: 0.79 [95% confidence interval [CI]: 0.73-0.86]), which was similar at 12 months (HR: 0.80 [95% CI: 0.74-0.86]). Intensifiers tended towards greater adherence to baseline therapy (90% [standard deviation (SD): 14.9] vs nonintensifiers 87% [SD: 16.0]), which decreased following intensification. CONCLUSIONS: Significant reductions in HbA1c were evident at 6 months and were greater in intensifiers vs nonintensifiers. Little additional clinical benefit was seen 12 months postintensification. Despite good treatment adherence, many participants failed to achieve target HbA1c; actions beyond improved adherence are needed to improve suboptimal HbA1c.

Predictors of quality of life and type 1 diabetes mellitus in Latin America: systematic review. / Predictores de calidad de vida y diabetes mellitus tipo 1 en Latinoamérica: revisión sistemática.

Diabetes mellitus is a serious public health problem worldwide. Type 1 diabetes mellitus is a metabolic disease which prevails in childhood; it is characterized by the persistence of high levels of glucose in the blood as a consequence of a deficit in the secretion or in the action of insulin. Type 1 diabetes mellitus has a chronic evolution and impacts the quality of life of patients. In order to describe the predictors of quality of life of patients with type 1 diabetes mellitus in Latin American countries, a systematic search was carried out in PubMed, Redalyc, SciELO, Scopus and Web of Science databases with the terms "SF-36", "WHOQOL" and "diabetes". A total of 2168 articles were identified, out of which only five were included in the qualitative analysis. It was found that comorbidities and complications decrease the quality of life of patients with type 1 diabetes mellitus, and factors such as adequate therapeutic adherence, good metabolic control, psychosocial and emotional well-being have a positive impact on the quality of life of these patients. Comorbidities and complications in patients with type 1 diabetes mellitus are the main predictors of poor quality of life.

La diabetes mellitus es un grave problema de salud pública en todo el mundo. Es una enfermedad metabólica de predominio en la infancia y se caracteriza por la persistencia de una glucemia elevada como consecuencia de un déficit en la secreción o en la acción de la insulina. Es de evolución crónica e impacta en la calidad de vida de los pacientes. Con el fin de describir los predictores de la calidad de vida de los pacientes con diabetes mellitus tipo 1 en los países latinoamericanos se realizó una búsqueda sistematizada en las bases de datos PubMed, Redalyc, SciELO, Scopus y Web of Science con los términos "SF-36", "WHOQOL" y "diabetes". Se identificaron 2168 artículos, de los cuales solo cinco fueron incluidos en el análisis cualitativo. Se encontró que la comorbilidad y las complicaciones disminuyen la calidad de vida de los pacientes con diabetes mellitus tipo 1, y que factores como la adecuada adherencia terapéutica, el buen control metabólico y el bienestar psicosocial y emocional impactan positivamente en la calidad de vida de estos pacientes. La comorbilidad y las complicaciones que presentan los pacientes con diabetes mellitus tipo 1 son los principales predictores de mala calidad de vida.

A case report of COVID-19 associated pulmonary mucormycosis.

Hospitalized patients with SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) are at risk for developing secondary fungal infections due to greater incidence of preexisting comorbidities and exposure to iatrogenic factors such as corticosteroid use. We present the case of a 44-year-old Hispanic female discovered unresponsive in her home that was found to have severe hyperglycemia with comorbid COVID-19 (coronavirus disease 2019) associated pneumonia. The patient was intubated and treated with several broad-spectrum antibiotics, remdesivir, and corticosteroids but had little improvement in her clinical status. Bronchoscopy was performed and revealed multiple necrotic lesions in the lungs. Endobronchial biopsy and bronchoalveolar lavage samples revealed pauciseptated hyphae consistent with zygomycetes. The patient was treated with multiple antifungals including voriconazole, micafungin, and amphotericin B. However, despite maximal medical therapy, the patient perished. This case highlights that clinicians must carry a high degree of suspicion and a low threshold to begin treatment for Mucor in diabetics and other immunosuppressed patients.

The Effect of Metformin Consumption on Mortality in Hospitalized COVID-19 patients: a systematic review and meta-analysis.

BACKGROUND AND AIMS: Diabetes is one of the most common comorbidities, and it is associated with poorer outcomes in patients with coronavirus disease 2019 (COVID-19). Preliminary findings showed that mortality was reduced in those who consume metformin compared to those who did not, and given its low cost and widespread availability; metformin is an attractive and potential agent to mitigate excessive risk in diabetic populations. METHODS: Several medical databases (Pubmed, EuropePMC, EBSCOhost, Proquest, Cochrane library) and two health-science preprint servers (preprint.org and Medrxiv) were systematically searched for relevant literature. RESULTS: Nine studies with 10,233 subjects were included in the qualitative and quantitative synthesis. Meta-analysis showed that metformin is associated with lower mortality in pooled non-adjusted model (OR 0.45 [0.25, 0.81], p = 0.008; I2: 63.9%, p = 0.026) and pooled adjusted model (OR 0.64 [0.43, 0.97], p = 0.035; I2: 52.1%, p = 0.064). CONCLUSION: The analysis showed that metformin consumption was associated with lower mortality. Randomized controlled trials are needed to confirm this finding.

Diabetes insípida nefrogénica inducida por litio: reporte de 2 casos en niños con trastorno del ánimo / Lithium-induced Nephrogenic Diabetes Insipidus: Report of 2 Cases in Children with Mood Disorder

La diabetes insípida (DI) es un síndrome caracterizado por poliuria y polidipsia asociado a la producción crónica de grandes volúmenes de orina diluida, secundario a una disminución de la secreción o acción de la hormona antidiurética (ADH) [1]. El litio es el principal fármaco implicado en la inducción de esta patología cuando se presenta de forma secundaria. [2]. Se presentan 2 reportes de casos de niños de 10 y 12 años con uso de litio por diagnóstico de trastorno del ánimo. Palabras Clave: Diabetes Melitus, trastornos del ánimo, nefrogénica, litio, hormona antidiurética

Diabetes insipidus (DI) is a syndrome characterized by polyuria and polydipsia associated with the production of large volumes of diluted urine, secondary to a decrease in the secretion or action of antidiuretic hormone (ADH) [1]. Lithium is the main drug involved in the induction of this pathology when it appears with a preventable cause [2]. Two case reports of children 10 and 12 years old with mood disorder and lithium use are presented with the intention of being alert to clinical manifestations and observation by caregivers.Key words: Diabetes insipidus, mood disorders, nephogenic, lithium, antidiuretic hormone.

The influence of diabetes and or periodontitis on inflammation and adiponectin level.

BACKGROUND: In Indonesia, most of diabetic patients had periodontitis and 75.3% of them had severe periodontitis. Previous study found that hyperglycemia and or local inflammation (such as periodontitis) modulated systemic pro-inflammatory and anti-inflammatory cytokines. AIMS: This study aimed to investigate the effect of DM and or periodontitis on systemic cytokines and adipocytokines levels. METHODS AND MATERIALS: A total of 57 participants with age of 29-71 years were recruited for this study. We divided them into three groups; DM-periodontitis (n = 22), periodontitis without DM (n = 16) and control (n = 19). All participants underwent physical examinations (BMI, WC, periodontal status examination) and laboratory examinations (FBG, fasting insulin, CRP, adiponektin, leptin, TNF-α and IL-10). RESULTS: The proportion of severe periodontitis were higher in DM-periodontitis group compared to periodontitis without DM (77.3% vs 6.2%). DM-periodontitis group had lower adiponectin levels than that of periodontitis without DM group [5860.78 ±â€¯4182.40 vs 9553.13 ±â€¯6794.73; p = 0.046]. TNF-α/IL-10 ratio was significantly higher in the periodontitis without DM compared to control group [1.96 (1.68-2.32) vs 1.55 (1.27-1.85); p = 0.015]. CONCLUSION: Local inflammation such as periodontitis, elevated systemic inflammatory markers (TNF-α/IL-10 ratio). Meanwhile chronic hyperglycemia alter adipocytokines level. The changes of systemic inflammation among diabetic group had not been shown yet in this study since some antidiabetic and antilipid drugs possess anti-inflammtory effect. Age, WC and FBG correlated with severe periodontitis. Adiponectin, leptin, TNF-α and IL-10 levels did not correlated with severe periodontitis.

Literacia em saúde e o autocuidado e autocontrolo no idoso com diabetes tipo 2 / Health literacy and self-care and self-monitoring in the elderly with type 2 diabetes

A diabetes sendo uma doença crónica, torna-se um grave problema de saúde pública a nível mundial, pelo aumento da sua incidência, e também pela sua elevada taxa de morbilidade e mortalidade. Capacitar a pessoa diabética para a gestão do regime terapêutico da doença crónica, é um objetivo da enfermagem. A diabetes tem uma prevalência superior na faixa etária dos 65 ou mais anos, sendo necessário difundir a literacia em saúde para capacitação deste grupo (Sousa, Peixoto e Martins, 2008). O enfermeiro e particularmente o enfermeiro especialista em enfermagem de saúde comunitária, tem grande responsabilidade em fomentar no utente a obtenção de conhecimentos e aptidões para o seu próprio autocuidado. A pertinência deste estudo prende-se com o facto de a diabetes ser uma doença crónica com fortes repercussões na vida da pessoa e tem como objetivo geral analisar os efeitos de um programa de literacia em saúde sobre a capacidade de controlo da diabetes no idoso. Este trabalho de investigação pretende avaliar os conhecimentos dos diabéticos acerca da sua doença e da sua capacidade para as atividades de autocuidado. Optamos por um estudo quasi-experimental de grupo único, com 2 momentos de avaliação, antes e após a intervenção. Recorremos a diferentes instrumentos: Questionário de Caracterização Sociodemográfica e Clínica, construído para o efeito, Questionário de Conhecimentos sobre Diabetes (DKQ-24), Escala de Atividade de Autocuidado com a Diabetes, e o Questionário de Literacia "Newest Vital Sign" e uma Checklist de Conhecimentos. Estes instrumentos foram aplicados em uma amostra emparelhada (n = 40) de pessoas diabéticas tipo 2, com 65 ou mais anos de idade e autónomas que se deslocaram à consulta de Enfermagem no ACES Cávado III Barcelos/Esposende em três momentos distintos. O perfil sociodemográfico dos inquiridos carateriza-se por ser maioritariamente constituído por pessoas do sexo feminino (52,5%), possuir o ensino básico (60,0%) como habilitações académicas e uma idade média de 72 anos. A situação profissional é predominante reformado(a) (92,5%), utilizando antidiabéticos orais (92,5%) como tipo de tratamento para a sua doença. Na vertente clinica, os inquiridos apresentaram valores médios anos como diabético de 10,1 anos. A hemoglobina glicada média é de 6,9 e IMC 29,6 kg/m2. Os resultados demonstraram a existência de diferenças estatisticamente significativas a nível dos conhecimentos sobre diabetes, sendo de realçar o facto de as mulheres no momento 1 terem 52,1% de respostas corretas, aumentando para 84,3% no momento 2, nos homens verificou-se a mesma tendência, tendo no 1 momento 59,0% de respostas corretas, evoluindo para 84,0% de respostas corretas no momento 2. Relativamente às atividades de autocuidado com a diabetes foram encontradas diferenças estatisticamente significativas nas atividades alimentação, alimentação específica e cuidados com os pés. A nível da literacia em saúde na 1ª avaliação os idosos que constituem a amostra situavam-se a um nível de alta probabilidade de literacia limitada e após a intervenção evoluíram para o nível de possibilidade de literacia limitada. Na Checklist de Conhecimentos em termos globais, as mulheres e os homens apresentam, respetivamente, 91,2% e 94,2% de respostas corretas.

Since diabetes is a chronic disease, it is a serious public health problem worldwide, due to the increasing of its incidence, and also for its high morbidity and mortality rate. Empowering the diabetic person to manage the therapeutic regimen of chronic disease becomes a nursing goal. Diabetes has a higher prevalence in the age group of 65 or over, and it is necessary to disseminate health literacy to enable this group (Sousa, Peixoto e Martins, 2008). The nurse and particularly the nurse specialist in community health nursing has a great responsibility in encouraging the patient to obtain knowledge and skills for their own self-care. The relevance of this research is knowing that diabetes is a chronic disease that has strong repercussions in the daily life of a person, therefore the general objective of this research is to analyze the effects of a health literacy program on the ability of the elderly diabetic to control the disease. This research aims to evaluate the knowledge of diabetics about their disease and their capacity for self-care activities. Therefore we optioned for a quasi-experimental study of a single group, with 2 evaluation moments, before and after the intervention. We used different instruments: Sociodemographic and clinical characterization questionnaire, constructed for this purpose, Diabetes Knowledge Questionnaire (DKQ-24), Diabetes Self-Care Activity Scale, and the "Newest Vital Sign" Literacy Questionnaire and a Checklist of Acquired Knowledge. These instruments were applied in a paired sample (n = 40) of type 2 diabetic patients, aged 65 years and older, who went to the Nursing Consultation at ACES Cávado IIII Barcelos / Esposende at three different times. The sociodemographic profile of the respondents is characterized by being mostly female (52.5%), have primary education (60.0%) and an average age of 72 years. The participants of the sample were predominantly retired (92.5%), using oral anti-diabetic medication (92.5%) as the type of treatment for their disease. On the clinical side, respondents presented mean values of 10.1 years as diabetic patients. The mean glycated hemoglobin is 6.9 and BMI 29.6 kg / m 2. The results showed statistically significant differences in knowledge about diabetes, with the women at the first evaluation presenting 52.1% of correct answers, increasing to 84.3% at the second evaluation, the men's sample demonstrated the same trend, with 59.0% of correct answers at the first evaluation, evolving to 84.0% of correct answers at the second evaluation. Regarding the self-care activities with diabetes, statistically significant differences were found on the subscale General Diet, Specific Diet and Foot Care Activities. As for the level of health literacy in the first evaluation, the elderly sample were at a high probability of limited literacy level and after the intervention, they evolved to the level of limited literacy. In overall the Checklist of Acquired Knowledge, the women and men present respectively, 91.2% and 94.2% of correct answers.

Exenatida e exendina(9-39) oriundos do lagarto venenoso Heloderma suspectum e seus efeitos sobre a qualidade espermática de ratos obesos e diabéticos / Exenatide and exendin(9-39) from the poisonous lizard Heloderma suspectum and its effects on sperm quality in obese and diabetic rats

The effects of exenatide (EXE) and exendin(9-39) (EXE9), peptides isolated from poisonous lizard H. suspectum on obesity and diabetes mellitus on male fertility are still poorly understood. The aim of this study was to evaluate the effects of EXE and EXE9 on parameters that contribute to sperm quality in hypothalamic injury-induced obesity (MSG) and hypercaloric diet (DIO) as well as streptozotocin-induced diabetes mellitus (STZ). Obese and diabetic rats received 10μg EXE / kg or 100μg EXE9 / kg sc daily or remained untreated for 20 days. Healthy rats at same age for each experimental models were used for comparison, only MSG model used healthy rats treated with exenatide. Biometric and glucoregulatory parameters treated with EXE (STZ) and EXE9 (STZ, DIO, MSG) were evaluated. Blood, testes and tail of the epididymis were collected. Sex hormones, leptin and insulin were evaluated by ELISA. Sperm were obtained from the epididymal tail by washing with HTF culture medium. The percentage of abnormal sperm morphology was analyzed under a phase contrast microscope. Functional analyzes of sperm were performed only STZ and MSG models. Sperm kinetics was evaluated by Computer Aided Analysis. The EXE-treated STZ group (STZ-E) improved the biometric parameters, glycemic control as well as the morphology, functionality and kinetics of mature sperm and EXE9 (STZ-E9) has an EXE effect on essential parameters for maintaining sperm quality. DIO showed impaired sperm quality, but there were occasional changes in the parameters that affect sperm quality. DIO-E improved sperm quality, suggesting that the antiobesogenic, antidislipidemic, and antidiabetogenic action of EXE restored the accuracy of the pathway of mature sperm, whereas treatment with EXE9 did not dramatically affect sperm kinetics, but was unable to restore path accuracy. EXE, through glucoregulatory improvement in MSG, has beneficial effects on hormone levels as well as sperm morphology, functionality and kinetics. Negative changes caused by EXE9 in glycorregulatory parameters, exacerbated increase in mass of periepididimal adipose tissue deposition, decreased testosterone and FSH plasma levels, with consequences on kinetics negatively affect sperm quality. EXE has been shown to be an excellent therapeutic agent to be used for beneficial effects on sperm quality in obese and diabetic patients. Results of treatment with EXE9 similar to those obtained with EXE in some evaluated parameters suggest two hypotheses (1) the use of an alternative to classical receptor; or (2) a dose-dependent situation if the dose of EXE9 administered is not sufficient for its action as an antagonist in a given organ and / or tissue. Therefore clinical research is needed to deepen the knowledge as well as the use of exenatide in a new incretinomimetic function as therapy.

Os efeitos da exenatida (EXE) e da exendina(9-39) (EXE9), peptídeos isolados do lagarto venenoso H. suspectum sobre a obesidade e diabetes melito na fertilidade masculina ainda são pouco compreendidos. O objetivo deste estudo foi avaliar os efeitos da EXE e da EXE9 sobre parâmetros que contribuem para a qualidade espermática na obesidade induzida por injúria hipotalâmica (MSG) e dieta hipercalórica (DIO) bem como no diabetes melito induzido por estreptozotocina (STZ). Ratos obesos e diabéticos receberam 10μg EXE/kg ou 100μg EXE9/kg sc diariamente ou permaneceram sem tratamento por 20 dias. Ratos saudáveis de mesma idade para cada modelo experimental foram utilizados para comparação, somente para o modelo MSG houve ratos saudáveis tratados com exenatida. Foram avaliados parâmetros biométricos e glicorregulatórios tratados com EXE (STZ) e EXE9 (STZ, DIO, MSG). Sangue, testículos e cauda do epidídimo foram coletados. Hormônios sexuais, leptina e insulina foram avaliados por ELISA. Os espermatozoides foram obtidos da cauda epididimal por lavagem com meio de cultura HTF. A porcentagem de morfologia anormal dos espermatozoides foi analisada sob um microscópio de contraste de fase. Foram realizadas análises funcionais dos espermatozoides somente para os modelos STZ e MSG. A cinética espermática foi avaliada pela Análise Assistida por Computador. O grupo STZ tratado com EXE (STZ-E) melhorou os parâmetros biométricos, controle glicêmico bem como a morfologia, funcionalidade e cinética de espermatozoides maduros e EXE9 (STZ-E9) possui efeito contrário a EXE em parâmetros essenciais para manutenção da qualidade espermática. DIO apresentou comprometimento da qualidade espermática, porém foram alterações pontuais nos parâmetros que afetam a qualidade espermática. DIO-E melhorou a qualidade espermática, sugerindo que a ação antiobesogênicao, antidislipidêmico e antidiabetogênico de EXE restaurou a acurácia da trajetória do espermatozoide maduro, já o tratamento com EXE9 não afetou drasticamente a cinética espermática, mas foi incapaz de restaurar a acurácia da trajetória. EXE, através da melhora glicorregulatória em MSG, tem efeitos benéficos nos níveis hormonais, bem como na morfologia, funcionalidade e cinética dos espermatozoides. As alterações negativas causadas por EXE9 nos parâmetros glicorregulatórios, aumento exacerbado da massa do depósito de tecido adiposo periepididimal, diminuição dos níveis plasmáticos de testosterona e FSH, com consequências sobre a cinética repercutem negativamente sobre a qualidade dos espermatozoides. A EXE mostrou-se um excelente agente terapêutico para ser utilizado em busca de efeitos benéficos sobre a qualidade espermática em obesos e diabéticos. Os resultados do tratamento com EXE9 similares aos obtidos com EXE em alguns parâmetros avaliados sugerem duas hipóteses (1) a utilização de um receptor alternativo ao clássico; ou (2) uma situação dose-dependente no caso da dose de EXE9 administrada não ser o suficiente para sua ação como antagonista em determinado órgão e/ou tecido. Portanto são necessário pesquisas clínicas para aprofundar o conhecimento bem como a utilização da exenatida em uma nova função incretinomimética como terapia.

Considerations for the Development of Mobile Phone Apps to Support Diabetes Self-Management: Systematic Review.

BACKGROUND: There is increased research interest in the use of mobile phone apps to support diabetes management. However, there are divergent views on what constitute the minimum standards for inclusion in the development of mobile phone apps. Mobile phone apps require an evidence-based approach to development which will consequently impact on their effectiveness. Therefore, comprehensive information on developmental considerations could help designers and researchers to develop innovative and effective patient-centered self-management mobile phone apps for diabetes patients. OBJECTIVE: This systematic review examined the developmental considerations adopted in trials that engaged mobile phone applications for diabetes self-management. METHODS: A comprehensive search strategy was implemented across 5 electronic databases; Medline, Scopus, Social Science Citation Index, the Cochrane Central Register of Controlled Trials and Cumulative Index of Nursing and Allied Health Literature (CINALHL) and supplemented by reference list from identified studies. Study quality was evaluated using the Joanna Briggs Critical appraisal checklist for trials. Information on developmental factors (health behavioral theory, functionality, pilot testing, user and clinical expert involvements, data privacy and app security) were assessed across experimental studies using a template developed for the review. RESULTS: A total of 11 studies (10 randomized controlled trials and 1 quasi-experimental trial) that fitted the inclusion criteria were identified. All the included studies had the functionality of self-monitoring of blood glucose. However, only some of them included functions for data analytics (7/11, 63.6%), education (6/11, 54.5%) and reminder (6/11, 54.5%). There were 5/11(45.5%) studies with significantly improved glycosylated hemoglobin in the intervention groups where educational functionality was present in the apps used in the 5 trials. Only 1 (1/11, 9.1%) study considered health behavioral theory and user involvement, while 2 (2/11, 18.1%) other studies reported the involvement of clinical experts in the development of their apps. There were 4 (4/11, 36.4%) studies which referred to data security and privacy considerations during their app development while 7 (7/12, 63.6%) studies provided information on pilot testing of apps before use in the full trial. Overall, none of the studies provided information on all developmental factors assessed in the review. CONCLUSIONS: There is a lack of elaborate and detailed information in the literature regarding the factors considered in the development of apps used as interventions for diabetes self-management. Documentation and inclusion of such vital information will foster a transparent and shared decision-making process that will ultimately lead to the development of practical and user-friendly self-management apps that can enhance the quality of life for diabetes patients.