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Background: Leptin has a great effect on bone through direct or indirect involvement in bone remodeling. Considering the ambiguities that exist regarding the effect of leptin on bone and bone-related diseases including osteoporosis, in this study, we aimed to conduct a systematic review of various studies on the effect of leptin on osteoporosis, which may find an answer to the existing ambiguities. Methods: The search was performed to review studies on the effects of leptin on osteoporosis by using several databases including Scopus, PubMed, Web of Science, and Google Scholar. Electronic searches were conducted on 5 Jan 2023. There was no limit on the publication date of the articles. The risk of bias for the animal study was assessed with the CAMARADES checklist, and the study quality assessment was also assessed based on the guidelines for in vivo experiments (ARRIVE). In this study, the risk of bias (quality) of human studies was assessed using the quality assessment checklists by NHLBI. Results: Overall, 34 articles were included for data extraction and quality assessment. Overall, 27 human studies and seven animal studies were included in the article. The results of most of the studies conducted in this study showed that leptin has a physiological role in maintaining bone mass and better bone quality and reduces bone marrow adipogenesis and increases bone mineral density (BMD). As plasma leptin levels increased, BMD values or bone formation biomarkers increased. Conclusion: Leptin has an inhibitory role against bone resorption and increasing osteoprotegerin (OPG) levels, which, as a result, maintains bone density and reduces osteoclast activity, and has a positive relationship with increasing osteocalcin.
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Background: Hand injury as an important concern for the surgeon and the patient requires proper and timely treatment to prevent complications such as infection and adhesions, and with a proper rehabilitation program, the patient returns to maximum function as soon as possible. We aimed to investigate the short-term and long-term treatment results of deep flexor tendon repair in in zone II. Methods: This retrospective study was performed on 34 patients with 45 injured fingers in the zone II referred to Ahvaz Imam Khomeini Hospital, Ahvaz, Iran during 2017-2019. The results of deep flexor tendons repair in two groups, immediate and delayed primary repair were assessed. Results: The mean age of the patients was 27.76 years. There was no significant remarkable between male and female in the incidence of complications such as infection, tendon rupture and adhesions. 29.4% (n=10) had poor outcome, 8.8% (n=3) had fair outcome, 29.4% (n=10) had good outcome and 32.4% (n=11) had excellent outcomes. 26.5% had adhesion and infection rate was 11.8%. Conclusion: Among surgeons, there is consensus for the primary repair of tendon injury, but there was no significant difference between the results of immediate and delayed primary repair. Although physiotherapy has been suggested as an effective factor in improving hand function, its positive effect on the range of motion of the fingers has not been proven.
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This systematic review aimed to qualitatively synthesize recent randomized controlled trials (RCTs) regarding the effect of topical application and oral intake of herbal products on the healing of diabetic foot ulcer (DFU). Also, we sought to pool the obtained findings in a meta-analysis using a random-effects model, if RCTs were relatively comparable and homogenous. A comprehensive search was performed on five electronic data sources from their inception through 23 January 2024. The RCTs, without restriction on the country of origin, were included if they compared the effect of administering standard treatments and/or placebo (i.e. control condition) to applying standard treatments and/or herbal products in topical or oral routes (i.e. experimental condition). Out of 1166 retrieved records, 28 RCTs were included. Studies used different poly and single herbal formulations. Based on the meta-analysis, administration of standard care plus daily dressing of the ulcer site with olive oil for 28 days significantly increased the total ulcer healing score (3 RCTs; weighted mean difference [WMD] = 89.30; p < 0.001), raised frequency of complete ulcer healing (2 RCTs; risk ratio [RR] = 12.44; p = 0.039) and declined ulcer degree (3 RCTs; WMD = -22.28; p = 0.002). Also, daily use of the bitter melon leaf extract in oral form for 28 days significantly increased the total ulcer healing score (2 RCTs; WMD = 0.40; p = 0.001). Additionally, based on qualitative synthesis, the adjuvant use of herbal agents seems an intriguing choice to manage DFU. Nonetheless, considering the undesirable methodological quality of most studies and the high heterogeneity in administered herbal formulations, more robust trials are required to build a solid conclusion regarding the use of herbal products for healing DFU.
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Diabetes Mellitus , Pé Diabético , Humanos , Pé Diabético/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Úlcera/tratamento farmacológico , Bandagens , Administração Oral , Diabetes Mellitus/tratamento farmacológicoRESUMO
INTRODUCTION: Low-energy proximal femur fractures in elderly patients result from factors, like osteoporosis and falls. These fractures impose high rates of economic and social costs. In this study, we aimed to build predictive models by applying machine learning (ML) methods on radiomics features to predict low-energy proximal femur fractures. METHODS: Computed tomography scans of 40 patients (mean ± standard deviation of age = 71 ± 6) with low-energy proximal femur fractures (before a fracture occurs) and 40 individuals (mean ± standard deviation of age = 73 ± 7) as a control group were included. The regions of interest, including neck, trochanteric, and intertrochanteric, were drawn manually. The combinations of 25 classification methods and 8 feature selection methods were applied to radiomics features extracted from ROIs. Accuracy and the area under the receiver operator characteristic curve (AUC) were used to assess ML models' performance. RESULTS: AUC and accuracy values ranged from 0.408 to 1 and 0.697 to 1, respectively. Three classification methods, including multilayer perceptron (MLP), sequential minimal optimization (SMO), and stochastic gradient descent (SGD), in combination with the feature selection method, SVM attribute evaluation (SAE), exhibited the highest performance in the neck (AUC = 0.999, 0.971 and 0.971, respectively; accuracy = 0.988, 0.988, and 0.988, respectively) and the trochanteric (AUC = 1, 1 and 1, respectively; accuracy = 1, 1 and 1, respectively) regions. The same methods demonstrated the highest performance for the combination of the 3 ROIs' features (AUC = 1, 1 and 1, respectively; accuracy =1, 1 and 1, respectively). In the intertrochanteric region, the combination methods, MLP + SAE, SMO + SAE, and SGD + SAE, as well as the combination of the SAE method and logistic regression (LR) classification method exhibited the highest performance (AUC = 1, 1, 1 and 1, respectively; accuracy= 1, 1, 1 and 1, respectively). CONCLUSION: Applying machine learning methods to radiomics features is a powerful tool to predict low-energy proximal femur fractures. The results of this study can be verified by conducting more research on bigger datasets.
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Fraturas Proximais do Fêmur , Humanos , Idoso , Idoso de 80 Anos ou mais , Compostos Radiofarmacêuticos , Tomografia Computadorizada por Raios X/métodos , Fêmur/diagnóstico por imagem , Estudos RetrospectivosRESUMO
BACKGROUND: Diabetes is one of the major public health concerns. Prediabetes can increase the risk of developing some non-communicable diseases such as type 2 diabetes. Given the increasing trend of prediabetes, it is critical to control it and prevent its complications. Curcumin is a major bioactive component of turmeric. Zinc is an antioxidant nutrient. The present trial aimed to evaluate the effect of curcumin and zinc co-supplementation along with a loss-weight diet on serum lipid profiles in overweight or obese patients with prediabetes. METHODS: Eighty-four participants were randomized to four groups (curcumin (500 mg/day), zinc (30 mg/day), "curcumin and zinc", and placebo) for 90 days. Serum total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides (TG), non-HDL, HDL/LDL ratio, weight, BMI, waist circumstance (WC), hip circumstance (HC), physical activity (PA) and dietary intake were determined pre and post-intervention. This study will be conducted at Yazd Diabetes Research Clinic, Shahid Sadoughi University of Medical Sciences. RESULTS: Totally, 82 participants were included in the final analysis. After the adjusted PA effect, changes in serum TG (adjusted p = 0.001), LDL (adjusted p = 0.035), non-HDL (adjusted p = 0.003), HDL/LDL ratio (adjusted p = 0.002), and HDL (adjusted p < 0.0001) revealed a significant difference between the groups. However, the changes in weight (adjusted p = 0.004) and BMI (adjusted p = 0.006) were significant but the changes in dietary intake, PA, WC, and HC were non-significant (adjusted p ≥ 0.05). Despite that there was a significant difference for post-intervention HDL levels (adjusted p = 0.016), other lipid profiles showed no significant difference (adjusted p ≥ 0.05). CONCLUSION: The beneficial effects of "curcumin and zinc" co-supplementation was reported for the changes of some lipid profiles (TG, LDL, HDL, non-HDL, and HDL to LDL ratio), BMI, and weight with no positive effects on TC, dietary intake, PA, WC, and HC. Therefore, it may play a potential role in the prevention of macro and microvascular complications. Trial registration The project is a registered clinical trial (Registration number: IRCT20190902044671N1, Iranian Registry of Clinical Trials (IRCT), registered October 11, 2019.
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Background and Objective: Vitamin D accelerates myelin repair and recovery after nerve damage. This study aimed to evaluate the effect of vitamin D on the prognosis of patients with carpal tunnel syndrome (CTS). Methods: A randomized clinical trial was conducted in the orthopedic ward of Golestan and Imam Khomeini hospitals in Ahvaz for 2 years (from October 2018 to October 2020). Patients were divided into three groups: the first group received 1,000 units of vitamin D daily, the second group received 4,000 units of vitamin D per week for the first 4-6 weeks and then 2,000 units per month, and the third group received no vitamin D supplementation. The results were compared before and after 6 months between the study groups. Results: A total of 105 patients were included in the study, who were divided into three groups. The mean age of the patients was 39.24 ± 7.01 years (25-52 years). The mean level of the vitamin D in the control group was 25.40 ± 8.37 ng/mL, the group receiving 1,000 units/day was 26.71 ± 8.70 ng/mL, and the group receiving 50,000 units per week was 26.17 ± 8.63 ng/mL. The mean values of preoperative pain intensity, symptom severity, and functional status were almost the same in the three groups. These values were reduced after surgery in the two groups receiving the drug compared to the control group. Conclusions: The findings of the study showed that the administration of vitamin D supplementation in patients with CTS can significantly improve the postoperative symptoms of patients who underwent tendon release surgery and further improve the severity of symptoms and dysfunction of patients.
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BACKGROUND: Diabetic nephropathy (DN) has an increasing global prevalence with excessive health expenditure and burden. Exosomal mRNAs regulate intercellular communications and participate in the pathogenesis of various disorders like DN. This study aimed to assess the expression levels of ACE, ELMO1, and WT1 mRNAs in the blood extracellular vesicles (EVs) of DN patients and diabetic patients without nephropathy (DM group) in comparison to healthy controls and investigate their correlations with the severity of DN. METHODS: The performed investigation is a cross-sectional study of 256 participants including 103 DN patients, 100 DM patients, and 53 healthy controls. The quantification of WT1, ACE, and ELMO1 mRNAs in the blood EVs were executed using qRT-PCR. The ROC analysis was performed to determine the diagnostic accuracy of mRNAs. RESULTS: DN patients had significantly higher expressed WT1 mRNA (1.70-fold change) and lower expressed ACE mRNA (0.55-fold change) in the blood EVs compared to DM patients and controls. ELMO1 mRNA was not expressed in EVs of any groups. A positive correlation between WT1 mRNA level and urine Alb/Cr ratio (r = 0.602, p < 0.001) and a negative correlation between ACE mRNA expression and urine Alb/Cr ratio within DN patients (r = - 0.474, p < 0.001) was identified. The accuracy of WT1 mRNA and 1/ACE mRNA for predicting incipient DN was 0.63 (95% CI 0.55, 0.72) and 0.62 (95% CI 0.54, 0.71), and for predicting overt DN was 0.83 (95% CI 0.74, 0.92) and 0.75 (95% CI 0.66, 0.83), respectively. CONCLUSIONS: WT1 and ACE mRNAs level in blood EVs were predictors for early diagnosis of DN therefore their quantifications might be used to determine the severity of albuminuria and glomerular injuries.
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Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas , Vesículas Extracelulares , Proteínas Adaptadoras de Transdução de Sinal , Albuminúria , Biomarcadores , Estudos de Casos e Controles , Estudos Transversais , Nefropatias Diabéticas/genética , Humanos , Peptidil Dipeptidase A , RNA Mensageiro/genética , Proteínas WT1RESUMO
Management of prediabetes is a critical step to prevent type-2 diabetes. Curcumin and zinc have been studied as an antioxidant, antiinflammatory, and antidiabetic agents. In this clinical trial, 84 subjects were randomized into curcumin (500 mg), zinc (30 mg), zinc and curcumin, and placebo groups for 90 days. At the baseline and the end of the study, the outcomes (fasting plasma glucose (FPG), 2-hour postprandial glucose (2hpp), HbA1 C, insulin, insulin sensitivity (IS), insulin resistance (IR), ß-cell function (BCF), weight, body mass index (BMI), dietary intake, and physical activity (PA)) were measured. A hypocaloric diet and PA were recommended for all subjects. In total, 82 subjects completed the study. After the intervention, dietary intake, PA, weight, and BCF% did not show a significant difference among the groups. However, subjects taking only zinc and zinc and curcumin groups experienced decreased BMI compared to the placebo (p = .01 and .007, respectively). The three treated groups had improved FPG (p = .01), 2hpp (p = .003), HbA1C (p = .004), insulin (p = .001), IS% (p = .001), and IR (p < .001) compared to the placebo. Based on these results, zinc and curcumin supplementation exerted a beneficial effect on several key glycemic parameters.
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Curcumina , Suplementos Nutricionais , Resistência à Insulina , Estado Pré-Diabético , Zinco/farmacologia , Glicemia , Curcumina/farmacologia , Diabetes Mellitus Tipo 2/prevenção & controle , Dieta Redutora , Método Duplo-Cego , Humanos , Insulina , Obesidade/tratamento farmacológico , Sobrepeso/tratamento farmacológico , Estado Pré-Diabético/tratamento farmacológicoRESUMO
BACKGROUND: Due to the controversy over the effect of serum testosterone levels on coronary artery diseases, this survey explores the serum levels of free testosterone, luteinizing hormone, and follicle-stimulating hormone in candidates for coronary artery bypass graft compared with an age-matched control group and evaluates the associated factors in these participants. OBJECTIVE: To determine the testosterone level in elective coronary artery bypass grafting participants. MATERIALS AND METHODS: In this cross-sectional study, all male patients aged > 40 yr as candidates for elective coronary artery bypass grafting, who were referred to the Afshar Hospital, Yazd, Iran, from March 2018 to March 2019, were included. In total, 100 men were enrolled (50 cases and 50 controls). Their serum levels of free and total testosterone, luteinizing hormone, and follicle-stimulating hormone were measured and the results were compared. RESULTS: The findings indicated a significant difference between the two groups in total and free testosterone (both p < 0.001); they were lower in the case group. There was also a significant difference in the total testosterone of the participants with diabetes mellitus compared with no-diabetic individuals (p = 0.007). Free testosterone of diabetic subjects taking insulin was lower compared with those taking no insulin (p = 0.04). There was also an association between the body mass index and free testosterone, left ventricular ejection fraction and total testosterone, and a significant and negative relation between the duration of hospital admissions and free testosterone (p < 0.05). CONCLUSION: This study illustrates that participants with coronary artery disease bear a significantly low testosterone level in comparison with the healthy control group.
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BACKGROUND: The prevalence of prediabetes is increasing worldwide. Unfortunately, prediabetes is related to non-communicable diseases. A high risk of developing type 2 diabetes mellitus (T2DM) is reported in people with prediabetes. Curcumin, a polyphenol, might lead to its therapeutic role in obesity and some obesity-related metabolic diseases. Zinc is a trace element that plays a key role in the synthesis and action of insulin, carbohydrate metabolism, and decreasing inflammation. There has been no clinical trial of zinc and curcumin co-supplementation in patients with prediabetes. In previous studies, the single administration of zinc or curcumin has not been conducted on many of the studied markers in prediabetic patients. METHODS: The purpose of this randomized double-blind placebo-controlled clinical trial is to investigate the effect of curcumin and zinc co-supplementation on glycemic measurements, lipid profiles, and inflammatory and antioxidant biomarkers among 84 prediabetic patients with body mass index (BMI) between 25 and 35. Also, liver enzyme, serum zinc, urine zinc, blood pressure, anthropometric parameters, quality of life, adherence to co-supplementation, the side effects of co-supplementation, physical activity, and dietary intake will be assessed. Women or men (18-50 years old for men and 18 years to before menopause for women) will be followed for 3 months (90 days). This study will be conducted at Yazd Diabetes Research Clinic, Shahid Sadoughi University of Medical Sciences. DISCUSSION: A diet rich in antioxidants, polyphenols, and phytochemicals has been shown to have a beneficial role in prediabetes. According to the beneficial properties of curcumin or zinc and inadequate evidence, RCTs are needed to assess the effect of curcumin and zinc co-supplementation in native prediabetes patients. We hope the results of the present trial, negative or positive, fill this gap in the literature and facilitate the approach for a much larger, multi-center clinical trial. In conclusion, a synergic effect of co-supplementation along with a weight-loss diet may delay the progression to type 2 diabetes mellitus. TRIAL REGISTRATION: Iranian Registry of Clinical Trials (IRCT) IRCT20190902044671N1 . Registered on 11 October 2019.
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Curcumina , Diabetes Mellitus Tipo 2 , Estado Pré-Diabético , Adolescente , Adulto , Antioxidantes/efeitos adversos , Biomarcadores , Glicemia , Ensaios Clínicos Fase II como Assunto , Curcumina/efeitos adversos , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Suplementos Nutricionais , Método Duplo-Cego , Feminino , Humanos , Irã (Geográfico) , Lipídeos , Masculino , Pessoa de Meia-Idade , Obesidade/diagnóstico , Obesidade/tratamento farmacológico , Sobrepeso/diagnóstico , Sobrepeso/tratamento farmacológico , Estado Pré-Diabético/diagnóstico , Estado Pré-Diabético/tratamento farmacológico , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Adulto Jovem , ZincoRESUMO
BACKGROUND: Divorce is a social issue, which challenges not only the structure of family but also of a society. Studies have shown that infertility affects the marital boredom. In addition, resilience training and emphasizing on increasing piety (religiousness) can help to decrease this boredom. OBJECTIVE: This study aimed to evaluate the resilience training effects on the compromising of infertile couples' applicant for divorce. MATERIALS AND METHODS: In this cross-sectional study, 100 infertile couples who had requested for divorce and referred to the Center for consolidation of the family foundation were enrolled. Participants were randomly divided in two categories (n= 50/each): the case group received some consultation classes on social services as well as resilience training by a consultant in 5 sessions lasting 2 hr. In total, 10 hr of treatment; while the control group just received the consultation and social services. Canner and Davidson questionnaires were utilized as pre- and posttest in both groups. Groups answered the resilience's criterion of Canner and Davidson. RESULTS: The resilience training significantly increased the compromises made by couples in the case group compared to the control (p < 0.01). The results showed that 26% of members of the case group relinquished divorce, while 10% of control group members did the same; this difference was statistically significant (p < 0.01). CONCLUSION: The resilience training leads to increased psychological well-being elements and compromises in infertile couples.
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BACKGROUND: Based on the results of multiple studies, multiple signaling pathways is a major cause of resistence to chemotherapy in leukemia cells. Signal transducer and activator of transcription 5 (STAT5) is among these factors; it plays an essential role in proliferation of leukemic cells. METHODS: We obtained the materials used in our study via PubMed search from 1996 through 2019. The key search terms included "STAT5," "acute leukemia," "leukemogenesis," and "mutation." RESULTS: On activation, STAT5 not only inhibits apoptosis of leukemic cells via activating the B-cell lymphoma 2 (BCL-2) gene but also inhibits resistance to chemotherapy by enhancing human telomerase reverse transcriptase (hTERT) expression and maintaining telomere length in cells. It has also been shown that a number of mutations in the STAT5 gene and in related genes alter the expression of STAT5. CONCLUSION: The identification of STAT5 and the factors activated in its up- or downstream expression, affecting its function, contribute to better treatments such as targeted therapy rather than chemotherapy, improving the quality of life patients.
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Leucemia Mieloide Aguda/genética , Fator de Transcrição STAT5/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/patologia , Fator de Transcrição STAT5/genética , Transdução de SinaisRESUMO
BACKGROUND: Despite the certain role of both vitamin D and adiponectin in the regulation of insulin sensitivity, the interaction between these two agents has remained uncertain. OBJECTIVE: The present study aimed to determine whether vitamin D is able to change plasma adiponectin and affect glucose homeostasis and insulin sensitivity in first-degree relatives of subjects with type 2 diabetes. METHODS: This randomized clinical trial was conducted at Clinic of Shahid Sadoughi Hospital in Yazd, Iran, from January 25, 2012 to December 25, 2014. In this randomized, double-blinded controlled trial, 64 first-degree relatives of type 2 diabetic patients were assigned randomly to receive either vitamin D supplement (50000 IU vitamin D tablet weekly) plus lifestyle change as the intervention group (n = 32) or placebo plus lifestyle change as the control group (n = 32) for twelve weeks (three months). RESULTS: Fifty-three patients (28 in the intervention group and 25 in the control group) completed the study. Serum levels of vitamin D increased while insulin level and consequently insulin resistance (calculated by HOMA formula) significantly decreased in the case group (p-value <0.001 for all variables). Although the values of these three biomarkers showed a slight increase in control group, the changes were not statistically significant. The levels of the changes in other markers including adiponectin, Fasting Blood Sugar (FBS), triglyceride, and total cholesterol remained insignificant in both study groups after completing interventions compared with before interventions. CONCLUSION: This study showed that decreased insulin resistance is expected by administrating vitamin D supplement in first-degree relatives of the patients with diabetes mellitus. TRIAL REGISTRATION: The trial was registered at the Iranian Registry of Clinical Trials (http://www.irct.ir) with the IRCT ID: 201105176430N1. FUNDING: The authors received no financial support for the research or publication of this article.
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UV-VIS spectroscopic analysis of oligonucleotide DNA exposed to different magnetic fields was performed in order to investigate the relationship between DNA extinction coefficients and optical parameters according to magnetic-field strength. The results with the oligonucleotides adenine-thymine 100 mer (AT-100 DNA) and cytosine-guanine 100 mer (CG-100 DNA) indicate that the magnetic field influences DNA molar extinction coefficients and refractive indexes. The imaginary parts of the refractive index and molar extinction coefficients of the AT-100 and CG-100 DNA decreased after exposure to a magnetic field of 750 mT due to cleavage of the DNA oligonucleotides into smaller segments.
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Polinucleotídeos/química , Sequência Rica em At , Composição de Bases , Sequência Rica em GC , Campos Magnéticos , Refratometria , Espectrofotometria UltravioletaRESUMO
To achieve tight glycemic control in diabetic patients, it may be necessary to introduce insulin therapy much earlier in the disease course. Poor glycemic control is a risk factor for the development of diabetic complications. Many patients require insulin therapy after several years of disease in order to maintain good glycemic control and prevent complications. But many patients do not receive insulin therapy in a timely manner because of a negative appraisal of this treatment. Understanding the cause of this negative attitudes is necessary for better evaluation to overcome for this problem. The purpose of this study was to evaluate the reasons for insulin refusal among patients with type 2 diabetes. This is a descriptive cross-sectional study from Yazd Diabetes Research Center. 400 patients with type 2 diabetes who had an HbA1c ≥8.0% despite optimal oral therapy were identified that participated in this study. Data were obtained by patient interview using validated questionnaires. This study showed that Insulin refusal was common. 77% of participant reported being unwilling to take insulin if prescribed. Fear of injection is an important cause for insulin refusal among patients. Insulin refusal is an important problem among our patients with type 2 diabetes mellitus. Findings of this study suggest that interventions aimed at increasing insulin use should focus on injection-related concerns, education and correction of misconceptions.
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Diabetes Mellitus Tipo 2/tratamento farmacológico , Insulina/uso terapêutico , Recusa do Paciente ao Tratamento , Estudos Transversais , Humanos , Irã (Geográfico)RESUMO
Wolfram syndrome is the constellation of juvenile onset diabetes mellitus and optic atrophy, known as DIDMOAD (Diabetes Insipidus, Diabetes Mellitus, Optic Atrophy, and Deafness).Patients demonstrate diabetes mellitus followed by optic atrophy in the first decade, diabetes insipidus and sensorineural deafness in the second decade, dilated renal outflow tracts early in the third decade, and multiple neurological abnormalities early in the fourth decade.This study reports two siblings with late diagnosed wolfram syndrome with diabetes insipidus, diabetes mellitus, optic atrophy, deafness and severe urological abnormalities.In conclusion, cases having early onset insulin-dependent diabetes mellitus and optic atrophy together need to be evaluated with respect to Wolfram.