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Impaired glycemic control is a potential predictor for macro- and microvascular complications of diabetes, which could be recognized by glycemic variability. The aim of this 10-year prospective cohort study presented here is to gain a better understanding of the correlation between GV and diabetic peripheral neuropathy (DPN) as one of the most common complications of T2DM.Since February 2010, 1152 adult patients with T2DM have been followed-up. Baseline features, anthropometric measurements, and laboratory findings were collected and documented during ten years. The association between DPN incidence and glycemic profile variability was evaluated using cox regression analysis. The coefficient of variation of glycemic indices within subjects was calculated and compared using an independent sample t-test.Individuals who developed neuropathy had significantly higher mean levels of glycemic indices (HbA1c, FBS, and 2hpp), urinary albumin excretion, mean creatinine levels, and a longer duration of diabetes. A significant positive correlation between incidence of DPN and glycemic profile variability (cv-FBS10 %, cv-FBS20 %, cv-2hpp20 %, cv-HbA1c5 % and cv-HbA1c10 %) was revealed. Results also showed that higher variability of FBS was associated with the higher risk of neuropathy incidence (HR: 12.29, p-value: 0.045), which indicates that glycemic profile variability is an independent risk factor for DPN in patients with T2DM.Variability of glycemic profiles from a visit to visit, regardless of sustained hyperglycemia, was indeed a significant risk factor for DPN in diabetic type 2 patients. CV-FBS was the most critical glycemic variability indices for DPN development. more...

Obesity plays a major role in the pathogenesis and development of macro- and microvascular complications of type 2 diabetes (T2D) and type 1 diabetes (T1D). We aimed to assess the association between obesity and macrovascular and microvascular complications of diabetes.This study consisted of 111,830 patients (age range: 1-106) with diabetes including 10,641 T1D (3187 obese [38.2% men] and 7454 non-obese [45.5% men]) and 101,189 T2D (51,873 obese [27.5% men] and 49,316 non-obese [33.4% men]) from the National Program for Prevention and Control of Diabetes (NPPCD-2021) in Iran, who attended academic tertiary care outpatient clinics from February 2016 to April 2021. A pooled logistic regression model was used to examine the association between obesity and diabetic complications.Among patients with T1D, a significant association was found between obesity and cardiovascular disease (CVD), neuropathy, nephropathy and retinopathy (OR= 1.75, 1.56, 1.80 and 1.92, P-value= 0.001, 0.004, 0.001 and0.001, respectively). In T2D, a statistically significant association was found between obesity and CVD, neuropathy and nephropathy (OR= 1.63, 1.98, 1.21, respectively, P-values0.001).Obesity was independently associated with CVD, neuropathy and nephropathy in patients with T1D and T2D and with retinopathy only in T1D, to different degrees. The association between obesity and retinopathy and neuropathy was the strongest among T1D and T2D, respectively. Findings from this study suggest that obesity affects diabetic complications differently among the two types of diabetes, in terms of epidemiology and pathophysiology. This signifies the importance of different preventive and therapeutic approaches to obesity in T1D compared to T2D, on a national and global scale. more...

Diabetes mellitus and hypertension are highly prevalent among patients with severe COVID-19.To study the mortality risk of COVID-19 infection in patients with type 2 diabetes and additive effect of hypertension and obesity in the Iranian population.This was a cross-sectional survey of the national COVID-19 registry from the Iranian Ministry of Health. The medical status of 22 002 patients with COVID-19 between 1 March and 30 April 2020 was analysed.Patients with type 2 diabetes had a higher risk of mortality with an odds ratio (OR) of 1.67 [95% confidence interval (CI): 1.53-1.82, P0.001]. The risk of mortality was also high in patients with diabetes and hypertension, with an odds ratio of 1.76 (95% CI: 1.56-1.99, P0.001). The odds ratio of the risk of mortality in patients with diabetes, hypertension and obesity was 1.87 (95% CI: 1.35-2.58, P0.001).Type 2 diabetes, hypertension and obesity each predict mortality in Iranian patients with COVID-19, and when they are present together, patients have a greater risk of mortality.خطر الوفاة الناجمة عن الإصابة بكوفيد-19 لدى المرضى الإيرانيين المصابين بالنمط 2 من السكري وارتفاع ضغط الدم والسمنة.مهدي شدنوش، صغرا ربيع زاده، علي رضا إستغاماتي، منوشهر ناخجواني، نسرين بيات باريداري، مصطفى خشابي، أرمين رجب، فاطمة غامي.ينتشر داء السكري وارتفاع ضغط الدم انتشارًا كبيرًا بين المرضى المصابين بحالة وخيمة من كوفيد-19.هدفت هذه الدراسة إلى دراسة خطر الوفاة الناجمة عن الإصابة بكوفيد-19 لدى المرضى المصابين بالنمط 2 من السكري، والتأثير الإضافي لارتفاع ضغط الدم والسمنة لدى السكان الإيرانيين.أُجري مسح مقطعي للسجل الوطني الخاص بمرض كوفيد-19 في وزارة الصحة الإيرانية. وجرى تحليل الحالة الطبية لعدد 22002 من المرضى المصابين بكوفيد-19 في الفترة بين 1 مارس/ آذار و30 أبريل/ نيسان 2020.كان المرضى المصابون بالنمط 2 من السكري أكثر عرضة للوفاة بنسبة أرجحية 1.67 [فاصل ثقة 95٪: 1.53–1.82، القيمة الاحتمالية0.001]. وكان خطر الوفاة أيضًا أعلى لدى مرضى السكري وارتفاع ضغط الدم، بنسبة أرجحية 1.76 [فاصل ثقة 95٪: 1.56–1.99، القيمة الاحتمالية0.001). وبلغت نسبة أرجحية خطر الوفاة لدى مرضى السكري وارتفاع ضغط الدم والسمنة 1.87 (فاصل ثقة 95٪: 1.35–2.58، القيمة الاحتمالية0.001).يُنبئ كلٌ من النمط 2 من داء السكري وارتفاع ضغط الدم والسمنة بالوفيات لدى المرضى الإيرانيين المصابين بكوفيد-19، وعندما تترافق تلك الأمراض معًا، يزداد خطر وفاة المرضى.Risque de mortalité lié à l'infection par la COVID-19 chez les patients iraniens souffrant de diabète de type 2, d'hypertension et d'obésité.Le diabète sucré et l'hypertension sont très prévalents chez les patients atteints d'une forme grave de COVID-19.Étudier le risque de mortalité lié à l'infection par la COVID-19 chez les patients atteints de diabète de type 2 et l'effet additif de l'hypertension et de l'obésité dans la population iranienne.Il s'agissait d'une enquête transversale du registre national de la COVID-19 du ministère iranien de la Santé et de l'Éducation médicale. L'état de santé de 22 002 patients atteints de COVID-19 entre le 1Les patients atteints de diabète de type 2 présentaient un risque de mortalité plus élevé avec un odds ratio (OR) de 1,67 [intervalle de confiance (IC) à 95 % : 1,53-1,82, p0,001]. Le risque de mortalité était également plus élevé chez les patients diabétiques et hypertendus, avec un OR de 1,76 (IC à 95 % : 1,56-1,99, p0,001). L'odds ratio du risque de mortalité chez les patients diabétiques, hypertendus et obèses était de 1,87 (IC à 95 % : 1,35-2,58, p0,001).Le diabète de type 2, l'hypertension et l'obésité permettent respectivement de prédire la mortalité chez les patients iraniens atteints de COVID-19, et lorsqu'ils sont présents ensemble, les patients ont un risque de mortalité plus élevé. more...

Background Metabolic-associated fatty liver disease (MAFLD), one of the most common liver diseases, is detected in patients with concomitant hepatic steatosis and Type 2 Diabetes (T2D). We looked into the relationship between Fibrosis-4 (FIB-4) index and coronary artery diseases (CAD) in patients with MAFLD, to further look into the efficiency of FIB-4 in screening for CAD among patients with MAFLD. Method In this study, we included 1664 patients with MAFLD (T2D, who also had hepatic steatosis) during 2012–2022 and divided them into 2 groups; CAD and non-CAD. Demographic, Anthropometric indices, liver function tests, lipid profile and FIB-4 index of all patients were evaluated and compared. Result Among the 1644 patients (all have MAFLD), 364(21.4%) had CAD. Patients with MAFLD and CAD were more probable to be hypertensive, have longer duration of diabetes and be older (with p-values Conclusion This study showed that the FIB-4 score independently correlates with CAD in patients with MAFLD. more...

To evaluate the effectiveness of a Mediterranean dietary pattern on the incidence of macrovascular and microvascular complications of diabetes, namely cardiovascular disease (CVD), diabetic foot disorders, diabetic retinopathy, nephropathy, and neuropathy.This longitudinal study was conducted among 71392 adults with diabetes who attended academic tertiary-care outpatient clinics from February 2016 to March 2020 across Iran using the National Program for Prevention and Control of Diabetes database. Among them, 22187 patients with diabetes (type 1 and type 2) completed 2-11 follow-up visits after baseline registration. The association between adherence to a Mediterranean diet and diabetic complications was assessed using pooled logistic regression models. This association was adjusted for potential confounders. The effect of time was assessed using fractional polynomials.A total of 22187 participants were included in the analysis (30.22% men and 69.78% women) with either type 1 (mean age 50.7 years) or type 2 (mean age 59.9 years) diabetes. After adjustment for confounding variables, there was a negative correlation between adherence to a Mediterranean diet and the incidence of CVD among patients with type 1 diabetes (T1D) and 2 diabetes (T2D) (OR= 0.53, 95% CI: 0.37 - 0.75, p-value0.001 and OR= 0.61, 95% CI: 0.57 - 0.89, p-value0.001, respectively). Also, the diet had a statistically significant protective effect against incident symptomatic neuropathy (OR= 0.32, 95% CI: 0.23 - 0.43, p-value0.001, and OR= 0.68, 95% CI: 0.64 - 0.72, p-value0.001, respectively), nephropathy (OR= 0.42, 95% CI: 0.30 - 0.58, p-value0.001, and OR= 0.88, 95% CI: 0.80 - 0.96, p-value= 0.007, respectively), and retinopathy (OR= 0.32, 95% CI: 0.24 - 0.44, p-value0.001, and OR= 0.68, 95% CI: 0.61 - 0.71, p-value0.001, respectively) in T1D and T2D.The Mediterranean dietary pattern is associated with a lower incidence of CVD and microvascular complications (i.e. diabetic retinopathy, nephropathy, and neuropathy) among a cohort of patients with T1D and T2D in Iran. more...

Rheumatoid arthritis (RA) is a prevalent inflammatory disorder causing functional disabilities. Oxidative stress can cause inflammation and can also be induced by inflammation. Measuring oxidative stress markers could help better understand the pathophysiology of RA and may be used to define the disease severity.In this case-control study, 75 RA patients were selected among those referred to the rheumatology clinic. Patients were further categorized into two groups, with active and inactive disease according to the Disease Activity Score (DAS) 28. Forty healthy volunteered persons were selected as the control group. Blood samples were obtained, and advanced glycation end products (AGEs), advanced oxidation protein products (AOPPs), and ferric reducing ability of plasma (FRAP) were measured. The results were compared via student t-test and Chi-square.Mean ± SD values for AGEs, AOPP, and FRAP in cases and controls were 53.29 ± 6.82 vs. 44.43 ± 7.13 (p = 0.001), 146.08 ± 19.56 vs. 135.79 ± 14.23 (p = 0.004), and 967.13 ± 226.66 vs. 1012.87 ± 215.94 (p = 0.2), respectively. Mean ± SD values for AGEs, AOPP, and FRAP in patients with active disease and inactive disease were 53.32 ± 7.2 vs. 53.26 ± 6.48 (p = 0.9), 146.97 ± 17.56 vs. 145.06 ± 21.84 (p = 0.6), and 953.17 ± 217.09 vs. 983.09 ± 239.31 (p = 0.5), respectively.AGEs and AOPP but not FRAP were significantly increased in RA patients compared to healthy controls. There was no significant difference between AGEs, AOPP, and FRAP in RA patients with active and inactive disease. Key points • AGEs and AOPP but not FRAP were significantly increased in RA patients compared to healthy controls. • There was no significant difference between AGEs, AOPP, and FRAP in RA patients with active and inactive disease. more...

Coronary heart disease (CHD) is a major mortality risk factor in patients with diabetes. LDL cholesterol (LDL-C) is a major risk factor for the development of atherosclerosis. There is one apolipoprotein B (ApoB) molecule in each LDL particle. We aimed to evaluate the predictive value of the LDL-C/ApoB ratio for CHD in patients with type 2 diabetes (T2D).In this case-cohort study (apo)lipoproteins and glycemic indices were measured in 1058 individuals with T2D from February 2002 to March 2019, with a median duration of follow up of 10 years. Of 1058 patients with T2D, coronary heart disease occurred in 242 patients. Increased waist circumference, waist-to-hip ratio, and hemoglobin A1c, low-density lipoprotein cholesterol (LDL-C)/Apolipoprotein B (ApoB) ratio, presence of hypertension and metabolic syndrome, and insulin and statin use were more prevalent among patients with CHD (P 0.001). Logistic regression analysis showed that an LDL-C/ApoB ratio equal or lower than 1.2 could predict CHD independent of ASCVD risk score [adjusted OR:1.841, CI:1.257-2.698, P 0.001] when adjusted for multiple confounders. The atherogenic index of plasma (AIP) did not predict CHD.This study showed that LDL-C/ApoB ratio, but not the atherogenic index of plasma, may be considered as an indicator of CHD independent of the ASCVD risk score in patients with T2D. This finding merits further clarification to optimize preventive strategies for CHD. more...

Lysine treatment decreased diabetic complications associated with type 2 diabetes in the rat models of diabetes and in vitro. Herein, in a single-evaluator–blinded, randomized clinical trial, we investigated the effect of L-Lysine (Lys) intervention in type 2 diabetic patients. Two groups of type 2 diabetic patients (15 females and 10 males in each group) who were under treatment with glibenclamide and metformin underwent a short term (3 months), trial. The test group was orally administered with 3 g/day of Lys. Clinical and biochemical parameters of all patients were measured prior to and after the experimental period and were statistically analyzed. Among the serum parameters, FBS, insulin, HOMA-IR, HSP 70, LCAT, PON1, AOPP, and FRAP improved significantly in the test group. A significant decrease in HbA1c and urine glucose accompanying with positive correlations between HbA1c and FBS, fructosamine and both FBS and HbA1c, HOMA with both insulin and FBS, and FBS with urine glucose indicates that Lys prevents diabetes complications. There were no significant changes in the liver and kidney function tests indicating no toxicity of Lys for patients. In conclusion, Lys inhibited protein glycation, improved glycemic control, and increased antioxidant markers in type 2 diabetic patients; thus, it could be suggested for combinatorial therapy of diabetes with oral hypoglycemic agents to protect against vascular risk factors and other diabetic complications. more...

Proper glycaemic control can slow progression of diabetes complications. One of the main causes of poor glycaemic control is delayed initiation of insulin therapy.To explain the reasons for delayed insulin initiation based on a behavioural model using patients' innate psychological needs.We enrolled 151 patients with type 2 diabetes who had indications for insulin therapy. Thirty general practitioners (GPs) were included as care providers. Patients were studied by questionnaires evaluating components of self determination theory, such as competency, relatedness and autonomy. We also evaluated patients' attitudes towards insulin therapy using the Insulin Treatment Appraisal Scale questionnaire. GPs' attitudes towards insulin therapy were assessed with a different questionnaire.Competency of patients was scored as acceptable (14.44/20). Relatedness score was low at around 15.63/30. The findings suggested that the patients' intrinsic motivation was less than their extrinsic motivation (8.41/15 vs 15.03/20). The main barrier to insulin therapy on the patients' side was rejection of severity of illness (67.5%). According to GPs, low compliance (96.7%) was the main cause of delayed insulin prescription.We observed that patients do not have a proper understanding about their illness. Due to the low score of relatedness as a representative of patients and care providers' relationship, we highlight the importance of educating both about insulin therapy and how they can have the most effective relationship in this process.العوائق التي تَُول دون بدء العلاج بالأنسولين لداء السُّكَّري من النمط الثاني الذي لا يمكن ضبطه جيداً استناداً إلى نظرية تقرير المصير.أرمين رجب، بيجا خالو، صغرى رابي زاده، حميد العليمي، سالومي صالحي، رضا مجدزاده، حسين ميرميرانبور، أسد الله رجب، علي رضا إستغاماتي، منوچهر نخجواني.يمكن أن يؤدي ضبط سكر الدم على نحوٍ صحيح إلى إبطاء تفاقم مضاعفات السُّكَّري. ويُعد تأخر بدء العلاج بالأنسولين أحد الأسباب الرئيسية التي تحول دون الضبط الجيد لسكر الدم.هدفت هذه الدراسة إلى شرح أسباب تأخُّر بدء العلاج بالأنسولين بِناءً على نموذج سلوكي يستند إلى احتياجات المرضى النفسية الفطرية.شملت هذه الدراسة 151 مريضاً بالسُّكَّري من النمط الثاني تستدعي حالاتهم العلاج بالأنسولين. وشملت ثلاثين ممارساً عاماً يضطلعون بدور مُقدِّمي خدمات الرعاية. وخضع المرضى للدراسة عن طريق استبيانات لتقييم مكوِّنات نظرية تقرير المصير، مثل الكفاءة والارتباط والاستقلالية. كما أجرينا تقييماً لمواقف المرضى تجاه العلاج بالأنسولين باستخدام استبيان مقياس تقييم العلاج بالأنسولين. وقُيّمَت مواقف الممارسين العامِّين تجاه العلاج بالأنسولين باستخدام استبيان مختلف.حصلت كفاءة المرضى على درجة مقبولة (14.44 / 20)، فيما حصل الارتباط على درجة منخفضة تُقدَّر بنحو 15.63 / 30. وأشارت النتائج إلى أن الدافع الذاتي للمرضى كان أقلَّ من دوافعهم الخارجية (8.41 / 15 مقابل 15.03 / 20). وتَثَّل العائق الرئيسي الذي يحُول دون إقدام المرضى على العلاج بالأنسولين في عدم الاعتراف بشدة المرض (67.5٪). ووَفْقاً للممارسين العامِّين، كان انخفاض الامتثال (96.7٪) السبب الرئيسي لتأخُّر وصف الأنسولين.لاحظنا أن المرضى لا يتمتعون بفهمٍ صحيحٍ لمرضهم. ونظراً لانخفاض درجة الارتباط كممثل للعلاقة بين المرضى ومُقدِّمي خدمات الرعاية، فإننا نُسلّط الضوءَ على أهمية تثقيف كلٍ منهما بشأن العلاج بالأنسولين، وكيف يمكن الوصول إلى أفضل علاقة فعّالة بين الطرفين في إطار هذه العملية.Obstacles face à la mise en place de l’insulinothérapie dans le diabète de type 2 mal contrôlé selon la théorie de l’autodétermination.Un contrôle adéquat de la glycémie permet de ralentir la progression des complications du diabète. Le retard dans la mise en place de l’insulinothérapie constitue l’une des principales causes d’un mauvais contrôle de la glycémie.Expliquer les raisons du retard de la mise en place du traitement par insuline sur la base d’un modèle comportemental fondé sur les besoins psychologiques innés des patients.Nous avons recruté 151 patients atteints de diabète de type 2 pour lesquels l’insulinothérapie était indiquée. Une trentaine de médecins généralistes ont été inclus en qualité de prestataires de soins. L’étude a été menée au moyen de questionnaires évaluant des composantes de la théorie de l’autodétermination, telles que la compétence, l’affiliation et l’autonomie. Nous avons également évalué les attitudes des patients vis-à-vis de l’insulinothérapie à l’aide du questionnaire de l’échelle d’évaluation de l’insulinothérapie (Insulin Treatment Appraisal Scale). Les attitudes des médecins généralistes vis-à-vis de l’insulinothérapie ont été évaluées au moyen d’un questionnaire différent.La compétence des patients a été jugée acceptable (14,44/20). Le score se rapportant à l’affiliation était faible, à environ 15,63/30. Les résultats suggèrent que la motivation intrinsèque des patients était inférieure à leur motivation extrinsèque (8,41/15 contre 15,03/20). Du côté des patients, le rejet de la gravité de la maladie (67,5 %) constituait le principal obstacle à la mise en place de l’insulinothérapie. Selon les médecins généralistes, une faible observance (96,7 %) était la principale cause de retard dans la prescription d’insuline.Nous avons observé que les patients ont une mauvaise compréhension de leur maladie. En raison de la faiblesse du score concernant l’affiliation, en tant qu’élément représentant la relation entre les patients et les prestataires de soins, nous soulignons l’importance d’une meilleure sensibilisation des malades et soignants à l’insulinothérapie et de la manière de mettre en place une relation efficace. more...

We studied the effects of dipeptidyl peptidase 4 (DPP4) inhibitors on glycemic control in non-critically ill patients admitted to hospital. We searched MEDLINE and EMBASE for published studies in English up to July 2019. We included randomized clinical trials (RCTs) that compared DPP4 inhibitors plus insulin supplementation versus basal-bolus insulin regimen in the management of hyperglycemia non-critically ill patients with type 2 diabetes admitted to hospital. Mean difference (MD), relative risk (RR), and 95% confidence intervals (CI) were generated to interpret the data. Of 401 papers, four RCTs including 648 participants met inclusion criteria. There was no significant difference in mean daily blood glucose level between the two groups (MD 4.63; 95% CI = − 1.57, 10.83; p = 0.14) (I2 = 14%, p = 0.32). Total insulin dose per day was lower in patients receiving DPP4 inhibitors (MD − 14.27; CI = − 22.47, − 6.07; p = 0.001) (I2 = 92%, p = 0.001). Also, the number of insulin injection was significantly lower in patients receiving DPP4 inhibitors (MD − 0.79; CI = − 1.01, − 0.57; p = 0.001) (I2 = 0%, p = 0.68). The rate of hypoglycemia was not significantly different between the two groups (RR 0.60, CI = 0.34, 1.074; p = 0.08) (I2 = 37.3%, p = 0.18). Treatment failure was not significantly different between the two groups (RR 0.87, CI = 0.64, 4.8; p = 0.38) (I2 = 49%, p = 0.11). The results indicate that using DPP4 inhibitors plus basal or supplemental insulin in hospitalized patients is non-inferior to a standard basal-bolus insulin regimen and leads to a lower amount of insulin use and a lower rate of insulin injection. Limitations of this study were heterogeneity of baseline characteristics of included patients, small sample size, short duration, and non-uniformly defined outcome assessment parameters in the included studies. more...

Our aim in this study was to assess the relationship between serum lipoprotein(a) [Lp(a)] and apolipoproteins and the risk of developing diabetic retinopathy (DR).One thousand fifty-seven patients with type 2 diabetes were divided into 2 main groups and followed for 5 years: 637 patients without DR and 420 patients with DR. A group of patients with DR were then divided into 2 subgroups: 162 patients with nonproliferative DR (NPDR) and 163 patients with proliferative DR (PDR). The association between serum Lp(a) and apolipoproteins with NPDR and PDR was assessed using univariate and multivariate regression analyses. Receiver-operating characteristic curve analysis was performed based on the new cutoff values.There was a positive relationship between Lp(a) and the presence of DR as well as a negative correlation between ApoA and DR (p0.001 and p=0.03, respectively). We also found a positive association between ApoB and the severity of DR (p=0.008). ApoA1 had an area under the curve of 55.0% for the prediction of DR. The calculated cutoff values of ApoB/ApoA1 ratio (0.58 g/L) and ApoB (77.5 g/L) in detection of DR were lower than their standard cutoff values of 0.8 and 90 g/L, respectively. Also, the sensitivity of new cutoff values for ApoB and ApoB/ApoA1 ratio was higher than the standard value, but the specificity of the standard cutoff values for both was higher than our new cutoff value.Serum Lp(a) and ApoA1 levels were independently associated with DR, and serum ApoB correlated with severity of DR. These measurements can be used for assessment and early treatment of this vision-threatening complication of diabetes. more...

This study was designed to evaluate the meeting of ABC goals in patients with type 2 diabetes. The ABC goals were defined as meeting the HbA1c7%, systolic blood pressure130 mmHg and diastolic blood pressure80 mmHg, and LDL-C100 mg/dL. We also determined the associated factors with meeting the ABC goals, as well as the effectiveness of statin therapy.We designed a cross-sectional study of 2008 type 2 diabetes patients attending the diabetes clinics of Valiasr Hospital of Imam Khomeini Hospital Complex. Meeting ABC goals and their associated factors were analyzed from the registered data.At the end of the year 2014, 61.3% of patients met the HbA1c goal, which increased to 77.8% in 2017. Blood pressure of 79.5% of patients met the ADA recommendations by the end of the year 2014, reaching 86.6% in 2017. Moreover, 84.5% and 93.8% could reach the LDL-C goal in 2014 and 2017, respectively. The proportion for the patients meeting all three ABC goals were 23.2% and 42.1% in 2014 and 2017, respectively.The level of achievement of ABC goals in Iran is lower than expected and it requires a lot of programming effort and follow-up. As patients are followed over the years, controlling ABC becomes much more favorable. more...

Regarding the role of inflammation in progression of diabetes this study was conducted to investigate the association between inflammatory biomarkers such as nitric oxide (NO), tumor necrosis factor alpha (TNF-α), and high-sensitivity C-reactive protein (hs-CRP) with the chance of existence of diabetic retinopathy and its progression in patients with diabetes. A total of 83 patients with T2DM (Type 2 diabetes mellitus) were divided into three groups of patients with proliferative diabetic retinopathy (PDR), patients with non-proliferative diabetic retinopathy (NPDR) and patients without diabetic retinopathy (NDR) based on ophthalmologic funduscopic examination. Twenty six healthy controls were also enrolled. Blood samples were taken after 12 h of overnight fasting, NO, TNF-α, and hs-CRP were measured. Association of the level of these biomarkers with retinopathy was analyzed. The levels of TNF-α, NO and hs-CRP were higher among patients with diabetic retinopathy. Multinomial Logistic Regression model showed that TNF-α and NO could predict the presence of retinopathy among patients with diabetes when adjusted for hs-CRP, HbA1c, FBS, gender, total cholesterol, triglyceride, HDL, LDL, BMI, and age (respectively OR = 1.76, CI 95% = 1.01–3.02, p = 0.046 and OR = 1.12, CI 95% = 1.05–1.18, p more...

Smoking is among the top leading causes of morbidity and mortality worldwide. To date, studies on the association between smoking and diabetes complications and metabolic control have shown conflicting results. In this study, we aimed to assess the association of smoking with micro- and macrovascular complications of diabetes and lipid and glycemic indices.We used the National Program for Prevention and Control of Diabetes of Iran database of 99,651 adult patients with diabetes across Iran. Multiple logistic regression models were used to examine the association between smoking and diabetes complications including cardiovascular disease, neuropathy, nephropathy and retinopathy. This association was adjusted for age, sex, duration of diabetes, glycated hemoglobin (A1C), hypertension, hyperlipidemia, medication, obesity and type of diabetes.Smoking was associated with cardiovascular disease, nephropathy, retinopathy and neuropathy (odds ratios [ORs] for patients with type 1 diabetes were 1.51, 2.29, 2.70 and 2.40, respectively; for patients with type 2 diabetes, ORs were 1.27, 1.21, 1.51 and 1.70, respectively; all with p values0.001). Among patients with type 1 diabetes, smoking was significantly (p0.05) associated with A1C (OR, 2.12), 2-h postglucose level (OR, 1.30), triglycerides (OR, 1.48) and high-density lipoprotein (HDL) control (OR, 1.34). Among patients with type 2 diabetes, smoking was significantly associated with A1C (OR, 1.09) and HDL control (OR, 1.21).Smoking was associated with multiple diabetes complications including cardiovascular disease, neuropathy, nephropathy and retinopathy and worse A1C and HDL control in both patients with type 1 and type 2 diabetes. It was also associated with worse 2-h postglucose level and triglyceride control among patients with type 1 diabetes. Our findings signify that national programs for smoking prevention and cessation may be beneficial to diabetes control in Iran. more...

To investigate the effects of pentoxifylline (PTX) in combination with losartan compared to the high dose of losartan alone on serum markers of diabetic nephropathy such as HSP70, copeptin, CRP, and TNFα in patients with type 2 diabetes and nephropathy.A single-center, randomized, double-blind, open-label clinical trial was conducted. Sixty-two patients were eligible and allocated to "PTX + losartan" and "high-dose losartan" arms of the trial using software for random number generation. The first arm received 400 mg PTX two times a day (BD) plus 50 mg losartan daily, while the second arm received 50 mg losartan two times a day (BD) for 12 weeks. Comparison of the biomarkers' levels before and after treatment was done using paired sample t test variance. ANCOVA was applied to evaluate the comparative efficacy of the two interventions. The effect size was calculated and reported for each biomarker.Urine albumin excretion (UAE), hs-CRP, and HbA1c significantly decreased in both trial arms compared to the baseline measures. Copeptin and TNFα showed significant differences (after vs before) only in the losartan group (p = 0.017 and p = 0.043, respectively). The losartan arm was more successful in reducing TNFα, copeptin, HSP70, systolic blood pressure (SBP), and diastolic blood pressure (DBP) values (p = 0.045, effect size = 7.3%; p = 0.018, effect size 10.1%; p = 0.046, effect size 4.7%, p = 0.001, effect size 23%; p = 0.012, effect size 10.2%, respectively) and the PTX arm was associated with a superior reduction of UAE and hs-CRP levels (p = 0.018, effect size 9.1%; p = 0.028, effect size 9.2%, respectively).Add-on PTX to losartan may have more effective anti-inflammatory and anti-albuminuric roles and therefore may be more applicable in the management of diabetic nephropathy compared with high-dose losartan alone.Trial number IRCT 20121104011356N10. more...

Coronary heart disease (CHD) is one of the major causes of mortality and morbidity in patients with type 2 diabetes mellitus. In this study, we aimed to assess the association between visit-to-visit variability of fasting blood sugar (FBS), HbA1c, blood sugar 2 h post-prandial (BS2hpp), lipid indices, creatinine, systolic and diastolic blood pressure (SBP, DBP) and incident CHD in patients with type 2 diabetes during a median follow-up of ten years. The current case-cohort study consisted of 1500 individuals with type 2 diabetes, followed up for the occurrence of CHD from 2002 to 2019. The patients had at least four annual follow-ups during which glycemic and lipid profile were measured. Co-efficient of variance (CV) for each parameter was calculated by 10-21 measurements. Cox regression analysis was performed to assess the association between CV of glycemic indices, lipid profile, blood pressure, creatinine, weight and incident CHD during the follow-up period. Hazard ratios (HR) were adjusted for the confounding variables. Glycemic indices variability (i.e., CV-HbA1c, CV-FBS, and CV-BS2hpp), were significantly higher in the group with incident CHD (P=0.034, P=0.042, and P=0.044, respectively). Hazard ratios were 1.42 (95 % CI=1.13-2.09) for CV-HbA1c, 1.37 (95 % CI=1.02-2.10) for CV-FBS, and 1.16 (95 % CI=1.01-1.63) for CV-BS2hpp (P=0.012, P=0.046, P=0.038, respectively). Creatinine was significantly higher in the group with incident CHD (P=0.036) and it was significantly associated with higher incidence of CHD (HR=1.14, 95 % CI=1.02-2.17, P=0.048). Visit to visit variability of glycemic indices of the patients with type 2 diabetes is associated with incident CHD independent of their baseline and mean values. more...

The nuclear factor-kappa B (NF-κB) signaling participates in diabetes complications. Therefore, the reduction of NF-κB signaling may be a goal to prevent or improve them. Thus, we investigated the effects of acetylcysteine (AC), histidine (His), and their combination on the NF-κB expression and its different activators in type 2 diabetic rats.The survey was performed on 50 rats that were allotted equally into five groups composed of control, diabetic, diabetic treated with (AC, 0.06%), (His, 0.1%), and (ACHis) groups. Treated groups have received the treatments daily in drinking water for two months. Metabolic profile (glucose, insulin resistance indices, lipid profile, and cardiovascular indices) and renal dysfunction parameters (creatinine and urinary protein excretion) were measured. Plus, diverse glycation (early, intermediate, and end), oxidative stress (Oxidized LDL, Reduced glutathione), and inflammatory markers (interleukine-1β, myeloperoxidase, and NF-kβ expression) were determined.Glucose, insulin resistance indices, cardiovascular indices, renal dysfunction parameters, different markers of glycation, oxidative stress, and inflammation as well as NF-κB expression, were the lowest in the (ACHis) treated diabetic rats. Besides, the cited parameter was lower in the Ac treated one than His treated (The combination of AC and His had the most protective effect against diabetes complications and advantageous effect on metabolism, β-cell activity, and insulin function due to the most reductive effect on the NF-κB pathway rather than More than any of the amino acids alone. more...

Diabetes mellitus (DM) is associated with an increased risk of endometrial carcinoma (EC). Heat shock proteins have a role in the modulation of both diseases. The aim of this study was to investigate extracellular HSP70 (eHSP70) level alternations in patients with two different types of EC (endometrioid and non-endometrioid) with and without type 2 diabetes. In a case-control study, 88 participants were enrolled in four groups including: 18 EC patients with DM, 19 EC patients without DM, 29 patients with DM, and 22 healthy individuals. Blood samples were taken before surgery in cancer patients. Estradiol, eHSP70, sex hormone-binding globulin (SHBG), FBS, and HbA1c were assessed. Serum HSP70 level was higher in patients with diabetes (52.24 ± 14.2 ng/ml) compared to healthy controls (39.04 ± 6.96) ( more...

Colorectal cancer (CRC) as one the most common cancer type is associated with oxidative stress. Surgery is the only curative modality for early-stage CRC. The aim of this study was to evaluate the oxidative damage biomarkers as well as enzymatic and nonenzymatic antioxidants in patients with CRC before and after tumor resection and in healthy controls. 60 patients with stage I/II colorectal adenocarcinoma and 43 healthy controls were recruited in this study. We measured plasma levels of oxidative damage biomarkers, including advanced oxidation protein products (AOPP), advanced glycation end products (AGEs), malondialdehyde (MDA), and oxidized low-density lipoprotein (ox-LDL) at baseline and after tumor removal. We also evaluated the plasma activity of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) as enzymatic antioxidants and the ferric reducing antioxidant power (FRAP) assay for nonenzymatic antioxidant capacity. Patients with CRC had significantly higher AGE, AOPP, MDA, and ox-LDL and also FRAP levels and higher SOD and GPx and lower CAT activity levels compared to healthy controls (p<0.05). We did not observe any statistically significant correlation between redox biomarkers and the size and stage of the tumor. AGEs (72.49±4.7vs.67.93±8.8,p<0.001), AOPP (137.64±21.9vs.119.08±33.1,p<0.001), MDA (3.56±0.30vs.3.05±0.33,p<0.001), and ox-LDL (19.78±0.97vs.16.94±1.02,p<0.001) concentrations reduced significantly after tumor removal. The largest effect sizes were found in ox-LDL (d=−2.853, 95% CI 2.50-3.19) and MDA (d=−1.617, 95% CI 0.43-0.57). Serum FRAP levels (1097.5±156.7vs.1239.3±290,p<0.001) and CAT (2.34±0.34vs.2.63±0.38,p<0.001), GPx (102.37±6.58vs.108.03±6.95,p<0.001), and SOD (5.13±0.39vs.5.53±0.31,p<0.001) activity levels increased significantly after surgery. The largest effect sizes among antioxidants were seen in SOD (d=1.135, 95% CI 0.46-0.34) and GPx (d=0.836, 95% CI 0.35-0.23). This study indicated that patients with colorectal cancer had higher levels of oxidative stress and antioxidant activity compared to healthy controls. After surgical resection of tumor, we observed a substantial improvement in redox homeostasis. more...

Suboptimal blood pressure (BP) control in patients with type 2 diabetes is associated with adverse micro‐ and macrovascular complications. This study aimed to investigate the predictors of uncontrolled hypertension in an Iranian population with type 2 diabetes. This is a cross‐sectional study of 2612 patients with type 2 diabetes, including 944 patients with hypertension. Controlled and uncontrolled hypertension were assessed. Multivariate logistic regression modeling was used to determined independent predictors of uncontrolled hypertension. Of 2612 patients with type 2 diabetes, 944 (36.1%) patients had hypertension. Of all patients with hypertension, 580 (61.4%) were still on monotherapy. Uncontrolled hypertension was detected in 536 participants (56.8%). Patients with uncontrolled hypertension had significantly higher body mass index (BMI) (29.8±4.8 vs. 28.6±4.6), waist circumference (99.11±10.95 vs. 96.68±10.92), pulse pressure (67.3±17.3 vs. 48.4±10.7), total cholesterol (177.1±45.5 vs. 164.3±40.5), non‐HDL cholesterol (133.0±43.5 vs. 120.1±38.7), triglycerides (175.7±80.3 vs. 157.4±76.7), and Atherogenic Index of Plasma (AIP) (0.57±0.23 vs. 0.52±0.24) (p 200 mg/dl non‐HDL cholesterol had a significant correlation with uncontrolled hypertension (OR = 4.635, CI95%:1.781–12.064, p = .002). In conclusion, BMI, pulse pressure, total cholesterol, and non‐HDL cholesterol are significant predictors of uncontrolled hypertension in patients with type 2 diabetes. Also, ineffective monotherapy, medical inertia and patients’ non‐compliance were other contributors to the uncontrolled hypertension. more...

BackgroundTo date, anthropometric measures (i.e. body mass index (BMI), waist to hip ratio (WHR) and waist to height ratio (WHtR) have shown to be associated with prediction of incident hypertension. However, the difference in accuracy of these measures has been of controversy. We aimed to determine whether WHtR is a more accurate tool for HTN than WHR and BMI in patients with type 2 diabetes.Material and MethodsThe study population consisted of 1685 normotensive patients with T2DM. They were followed up for hypertension incidence for a mean of 4.8 years from April 2002 to January 2020. Cox regression was performed to assess the association between anthropometric measures (i.e., BMI, WHR, and WHtR) and incident hypertension during the follow-up period. Area under the ROC curve analysis was performed and optimal cutoff values were calculated using Youden index.ResultsWHtR and BMI were significantly associated with an increased risk of hypertension (HR=3.296(0.936-12.857), P < 0.001 and HR:1.050 (1.030-1.070), P < 0.001, respectively). The discriminative powers of each anthropometric index for HTN were 0.571 (0.540–0.602) for BMI, 0.518 (0.486–0.550) for WHR, and 0.609 (0.578–0.639) for WHtR. The optimal cutoff points for predicting HTN in patients with T2DM were 26.94 (sensitivity=0.739, specificity=0.380) for BMI, 0.90 (sensitivity=0.718, specificity=0.279) for WHR and 0.59 (sensitivity=0.676, specificity=0.517) for WHtR.ConclusionIn the current study WHtR was a more accurate screening tool for HTN compared to WHR and BMI in patients with type 2 diabetes. more...

AimTo evaluate the predictive value of the LDL-C/ApoB ratio for coronary heart disease (CHD) in patients with type2 diabetes (T2D).MethodsIn this case-cohort study, (apo)lipoproteins and glycemic indices were measured in 1058 individuals with T2D from February 2002 to March 2019, with a median duration of follow up of 10 years.ResultsOf 1058 patients with T2D, coronary heart disease occurred in 242 patients. Increased waist circumference, waist-to-hip ratio, and hemoglobin A1c, low-density lipoprotein cholesterol (LDL-C)/Apolipoprotein B (ApoB) ratio, presence of hypertension and metabolic syndrome, and insulin and statin use were more prevalent among patients with CHD (PConclusionThis study showed that LDL-C/ApoB ratio and Lp(a) each, but not the atherogenic index of plasma, may be considered as an indicator of CHD independent of ASCVD risk score in patients with T2D. This finding merits further clarification to optimize preventive strategies for CHD. more...

Background Type 2 diabetes mellitus (T2DM) is associated with an oxidative milieu that leads to increased lipid peroxidation. Main focus of this study was to understand levels and correlations of two oxidative stress indices, malondialdehyde (MDA) and oxidized low-density lipoprotein (ox-LDL) levels, in diabetes associated oxidative stress. Moreover we examined the impact of different HDL-C levels on this correlation. Material and methods A total of 151 patients with T2DM and 45 healthy adults were enrolled in this cross-sectional study. Fasting plasma glucose, total cholesterol, triglyceride, High-Density Lipoprotein (HDL C), low-density lipoprotein (LDL), ox-LDL and MDA were measured. Results Linear regression analysis revealed higher levels and a positive correlation between MDA and ox-LDL in patients with T2DM (p 3.57 nmol/ml and ox-LDL > 60.68 U/dl had significantly poorer lipid profile and diabetic nephropathy indices. Patients were stratified into four quartiles based on associated HDL levels. Ox-LDL and MDA showed significant positive correlation only in HDL levels below 35 mg/dl. Conclusions We attempted to investigate applicability of MDA and ox-LDL in predicting T2DM related oxidative stress. Present data strongly suggest that using both of MDA and ox-LDL increases their specificity in predicting oxidative milieu and diabetic nephropathy. Moreover, we showed that HDL levels above 35 mg/dl might have beneficial effect on oxidative reactions. more...

Background To explores the prevalence of autoantibodies (zinc transporter 8 autoantibodies (ZnT8A), antibodies to insulin (IAAs), glutamic acid decarboxylase autoantibody (GAD65)), the relation of the type of positive autoantibody and the number of positive autoantibodies with the glycemic and lipid profile of the patients with LADA (Latent Autoimmune Diabetes in Adults) and compares it to the metabolic profile of patients presenting with type 2 diabetes (T2DM). Methods 263 patients with T2DM were recruited for this cross-sectional study in Tehran, Iran. Data from patients included complete medical history, GAD65, ZnT8A, IAA and routine metabolic laboratory workup. Assay for autoantibodies were conducted using ELISA kits. The association between autoantibodies and glycemic and lipid profile of patients with diabetes was assessed using univariate and multivariate regression analysis. Results Our study revealed that among 263 patients with T2DM, 29 (11%) cases were positive for IAAs, 9 (3.4%) for ZnT8A, and 12 (4.6%) for GAD65. Six (2.3%) of the patients had triple positive antibodies. Patients with positive results were younger, had lower body mass index (BMI), c-peptide, triglyceride, low-density lipoprotein (LDL), and higher high-density lipoprotein (HDL), HbA1c and fasting blood glucose (FBG) levels. Triple antibody positivity was significantly associated with lower levels of C-Peptide, Triglycerides, FBG, and HbA1c compared to triple negative antibodies. Conclusion Patients with LADA positive for either of the autoantibodies (GAD65, ZnT8 and IAA) presented with worse glycemic control. Measurement of these autoantibodies can assist in discrimination of these patients and help with earlier control of glycemic profile. more...

Technetium thyroid uptake (TTU) is not inhibited by antithyroid drugs (ATD) and reflects the degree of thyroid stimulation. We intended to predict the relapse rate from hyperthyroidism based on TTU measurement.Out of 44 initially enrolled subjects, 38 patients aged 41.6 ± 14.6 with Graves disease (duration: 84 ± 78 months) completed the study. TTU was performed with 40-second imaging of the neck and mediastinum 20 minutes after injection of 1 mCi technetium-99m pertechnetate. TTU was measured as the percentage of the count of activity accumulated in the thyroidal region minus the mediastinal background uptake to the count of 1 mCi technetium-99m under the same acquisition conditions. Then methimazole was stopped and patients were followed. The optimal TTU cutoff value for Graves relapse prediction was calculated using Youden's J statistic.Hyperthyroidism relapsed in 11 (28.9%) patients 122 ± 96 (range: 15-290) days post-ATD withdrawal. The subjects in remission were followed for 209 ± 81 days (range: 88-390). TTU was significantly higher in patients with forthcoming relapse (12.0 ± 8.0 vs. 3.9 ± 2.0, P = .007). The difference was significant after adjustment for age, sex, history of previous relapse, disease duration, and thyroid-stimulating hormone (TSH) levels before withdrawal. The area under the receiver operative characteristic (ROC) curve was 0.87. The optimal TTU cutoff value for classification of subjects with relapse and remission was 8.7 with sensitivity, specificity, and positive and negative predictive value of 73%, 100%, 100%, and 90%, respectively (odds ratio [OR] = 10.0; 95% confidence interval [CI]: 3.4-29.3).TTU evaluation in hyperthyroid patients receiving antithyroid medication is an accurate and practical method for predicting relapse after ATD withdrawal.ATD = antithyroid drugs RIU = radio-iodine uptake TSH = thyroid-stimulating hormone TSI = thyroid-stimulating immunoglobulin TTU = technetium thyroid uptake. more...

Aims To investigate the associations between Lp(a), Apo A1, Apo B, and Apo B/Apo A1 ratio with micro- and macrovascular complications of diabetes. Methods and results In this case-cohort study, 1057 patients with type 2 diabetes (T2DM) were followed in the diabetes clinic of Vali-Asr Hospital from 2014 to 2019. The association between serum Lp (a) and apolipoproteins with cardiovascular disease (CVD), neuropathy, and nephropathy were assessed by using binary regression analysis. The ROC curve analysis was used to evaluate the predictive properties of proteins. Youden index was used to calculate cutoff values. Among patients with T2DM, 242, 231, and 91 patients developed CVD, neuropathy, and nephropathy, respectively. The serum Lp (a) level was positively correlated with the development of all three. (P-values = 0.022, 0.042, and 0.038, respectively). The Apo A1 level was negatively correlated with nephropathy. Among the biomarkers, Lp(a) had the highest AUC for prediction of CVD, neuropathy, and nephropathy. Calculated cutoff values of Lp(a), and Apo A1 levels were higher than the standard cutoff values. Conclusion Serum level of Lp(a) is a predictor for CVD, neuropathy, and nephropathy. Based on the calculated cutoff values in patients with T2DM, we should consider diabetic complications at higher levels of Lp(a). more...

Cushing's syndrome (CS) secondary to corticotropin releasing hormone (CRH) producing tumors is rare. In this paper we present an Iranian patient who was admitted to our hospital with classic signs and symptoms of CS. Laboratory evaluation revealed high serum and urine cortisol which could not be suppressed with dexamethasone. Abdominal CT scan revealed a mass in abdominal cavity. A percutaneous needle biopsy was performed and histopathologic evaluation revealed that the mass was a neuroendocrine tumor. A multi-disciplinary approach including resection of the mass, bilateral adrenalectomy somatostatin analogue and chemotherapy was applied for management of the disease. Extensive review of English literature focusing on the topic from 1971 to 2018 revealed that there have been only 75 similar cases. Clinical, laboratory, imaging, histopathologic characteristics and managements of these patients will also be discussed in this paper. more...

The relation between serum preptin, myostatin, insulin, and also homeostatic model assessmentinsulin resistance were examined in pre-diabetes persons and newly diagnosed patients with overt type 2 diabetes mellitus. A total of 84 subjects were included in the study and assigned into three groups: normoglycemic participants (group 1=27), pre-diabetes (group 2=30), and T2DM (group 3=29). Serum insulin, preptin, and myostatin levels were measured with immunoradiometric assay (IRMA), enzyme-linked immunosorbent assay (ELISA), and chemiluminescent immunoassay (CLIA), respectively. Patients with T2DM had higher levels of preptin compared to normoglycemic (461.25±53.90 vs. 407.54±54.78, P more...

Introduction: The aim of this study was to compare oxidized low-density lipoprotein (oxLDL) and blood glucose in very low and low levels of vitamin D.Methods: A total of 25 type-2 diabetic patients with very low serum levels of 25-hydroxy vitamin D (severe deficiency – more...

Background: The main purpose of this study was to investigate whether or not electron beam therapy (EBT) was an effective method in terms of moderating oxidative stress by reducing free radicals in BALB/c mice with type 1 diabetes mellitus.Methods: The study was performed on thirty BALB/c mice in three groups including normal control, diabetic control, and EBT treated. Before studying the effect of electron beam on the studied groups, optimal level of constant source-to-surface distance, as well as the effects of EBT on glutathione reductase (GR) structure and function were determined. After studying the structure and the function of GR protein with three methods including fluorometry, circular dichroism (CD), and activity assay methods, SSD 100 was selected for EBT. Glucose, advanced glycation end-products, GR, oxidative stress factors such as hydrogen peroxide, malondialdehyde, advanced oxidation protein products, oxidized low-density lipoprotein, and inflammatory factors were measured in the serum of all groups.Results: The results of in vitro study showed that electron beam therapy could increase glutathione reductase activity, which was not significant. Also, the results were compared between and within groups using one-way analysis of variance. Significant differences were observed for all variables measured between the normal control group and the other groups (P < 0.05). There was also no significant difference in blood glucose levels between the electron beam therapy treated group and the diabetic one (P > 0.05).Conclusion: The results suggested that electron beam therapy could be effective in reducing free radicals and oxidative stress. Electron beam therapy, as a complementary method, might aid in moderating the complications of diabetes mellitus.Keywords: Diabetes mellitus, Electron beam, Inflammatory factors, Oxidative stress more...

Background Albuminuria is one of the first asymptomatic clinical manifestations of microvascular damage in type 2 diabetes. High-sensitivity C-reactive protein (hs-CRP), Asymmetric dimethylarginine (ADMA), and nitric oxide (NO) are important risk factors for endothelial dysfunction. The aim of this study is to evaluate hs-CRP, ADMA, and NO levels and their correlations in patients with type 2 diabetes respect to their albuminuric states. Methods We quantified serum hs-CRP, ADMA, and NO levels in 40 microalbuminuric (urinary albumin excretion ≤ 30 mg/day and Results The mean value of albuminuria was 238 ± 58 mg/day in the microalbuminuric group and 12.6 ± 4.7 mg/day in the normoalbuminuric group. Creatinine was significantly higher and GFR was significantly lower in group with microalbuminuria than normoalbuminuria (p Conclusion Hs-CRP was higher in microalbuminuric patients with type 2 diabetes compare to normoalbuminuric group. Also we found changing association among ADMA, NO and hs-CRP from normoalbuminuric to albuminuric state which this finding may be linked to the role of basic inflammation in confounding some interactions and creating some new ones. more...

Aims/purpose Fibroblast growth factor 21 (FGF21) is a major metabolic regulator in the body that has been shown to be elevated in a number of metabolic disturbances including type 2 diabetes mellitus (T2DM) and the metabolic syndrome. However, little is known regarding the circulating levels of FGF21 in type 2 diabetic retinopathy (T2DR) and its association with the severity of the condition. Methods In a cross-sectional setting, 142 individuals, consisting of (1) T2DM patients without T2DR, (2) T2DM patients with T2DR, and (3) healthy control subjects were recruited for this study. Various clinical and biochemical parameters were assessed and entered for analysis. Results Serum FGF21 levels were significantly elevated in T2DM subjects without retinopathy (103.50 [75.75] pg/mL) compared with healthy controls (99.00 [126.75] pg/mL). Circulating FGF21 levels were comparable across different stages of T2DR (233.00 [109.00] for nonproliferative type 2 diabetic retinopathy [NPT2DR] vs. 215.00 [122.00] for proliferative type 2 diabetic retinopathy [PT2DR] groups, P = 361). FGF21, triglycerides, and duration of diabetes mellitus were significantly associated with T2DM in baseline models. However, after adjustment for potential confounders, in the final multivariate model, FGF21 emerged as the only significant factor associated with T2DM (OR = 13.772, 95% CI = 3.062–61.948, P = 001). Conclusions Serum FGF21 concentrations are markedly elevated in patients with T2RN. The association between FGF21 and T2DR appears to be independent of the effects of potential confounding variables. These findings may suggest FGF21 as a novel surrogate diagnostic biomarker in initial stages of T2DR (particularly with FGF21 values above 135.5 pg/mL). more...

Background The aim of the present study was to determine the prevalence of metabolic syndrome and its individual components among the Iranian adult population in 2011 and to investigate changes between 2007 and 2011. Methods Data from two rounds of the Surveillance of Risk Factors of Non-communicable Diseases national surveys conducted in 2007 and 2011 were pooled. Metabolic syndrome was defined according to International Diabetes Federation criteria. Results In 2007, the prevalence of metabolic syndrome among adults aged 25–64 years was 35.95 (95% confidence interval [CI] 34.27–37.63), which decreased to 32.96 (95% CI 30.73–35.18) in 2011 (P = 0.0108). Despite this overall decline, the prevalence of central obesity (P = 0.1383), raised triglycerides (P = 0.3058), and reduced high-density lipoprotein cholesterol (HDL-C; P = 0.5595) remained constant. There was a trend towards a decline in the proportion of individuals with increased blood pressure (P = 0.0978), and the proportion of adults with increased fasting plasma glucose (FPG) increased (P < 0.0001). In 2011, the prevalence of central obesity, raised triglycerides, reduced HDL-C, increased blood pressure and increased FPG was 51.88 (95% CI 48.97–54.79), 36.99 (95% CI 34.52–39.45), 54.72 (95% CI 50.87–58.57), 38.92 (95% CI 36.19–41.64), and 24.97 (95% CI 22.02–27.93) respectively. Conclusions Over the period 2007–11, the prevalence of metabolic syndrome has decreased slightly in Iran, although prevalence of increased FPG has increased significantly. One-third of the Iranian adult population is diagnosed with metabolic syndrome. more...

OBJECTIVES Wide pulse pressure (PP) is an independent predictor of coronary heart disease (CHD). However, the linearity of the relation between PP and CHD was not examined before. We aimed to examine this relation in patients with type 2 diabetes and/or hypertension. METHODS A total of 3120 patients (including 2607 with diabetes and 1586 with hypertension) were followed for 7.8 years. Physician-adjudicated first hard CHD event was the primary outcome. Cox regression analysis was used to investigate the association between PP and incident CHD. Restricted cubic splines were used to investigate nonlinear relations. RESULTS Four spline covariates were defined between 30, 40, 50, 60, and 70 mmHg. The null-hypothesis of the linearity of the relation between PP and CHD was rejected (P value = 0.004). The second, third, and fourth spline covariates were significant (P value = 0.02, P value = 0.02 and P value = 0.01, respectively), supporting a nonlinear relation in corresponding PP intervals. Patients with PP less than 45 mmHg and PP more than 55 mmHg had increased risk of future CHD event, compared with those with PP between 45 and 55 mmHg [hazard ratio (HR) = 1.33 (1.00-1.77) and HR = 1.67 (1.23-2.27), respectively]. This remained significant after controlling for systolic, diastolic, or mean arterial pressures in wide PP group. However, adjustment for traditional cardiovascular risk factors (especially age) attenuated the relation in those with wide PP. CONCLUSION The relation between PP and CHD is nonlinear in patients with type 2 diabetes and hypertension. Both narrow and wide PPs increase risk of future hard CHD events. The association between wide PP and CHD is independent from SBP, DBP, or mean arterial pressure. more...

Diabetes is associated with the excess formation of advanced glycation end-products (AGEs) and advanced oxidation protein products (AOPP), and low levels of ferric reducing ability of plasma (FRAP). However, the trend of oxidative and antioxidant markers levels according to diabetes duration is unclear.In a case-control study, 240 patients with diabetes and 100 healthy controls were enrolled. Patients were divided into four groups according to the duration of diabetes, including newly diagnosed, 1-5, 5-10, and 10-15 years. Serum AGEs, AOPP, and FRAP levels were compared among groups.AGEs and AOPP were higher and FRAP was lower in patients with diabetes compared to healthy controls. Serum levels of AGEs increased progressively with increasing in diabetes duration. AGEs levels were 68.97 ± 7.28% in newly-diagnosed, 73.43 ± 12.96% in 1-5 years and 80.44 ± 13.84% in 10-15 years of diabetes duration (pairwise p-values0.05). In linear regression analysis the correlation among AGEs, AOPP, FRAP, and diabetes duration remained significant after adjustment for age, BMI, HDL, HbA1c, waist circumference, microvascular complications, and coronary artery diseases. ROC analysis showed AGEs could predict the duration of diabetes when patients with 10-15 years duration of diabetes were compared to patients with 1-5 years duration of diabetes (AUC = 0.676, p-value = 0.003).Diabetes promotes AGEs, and AOPP production, independent of glycemic control and patients age. Serum levels of AGEs increase progressively with increasing duration of diabetes. AGEs may be helpful in estimating chronicity of diabetes. more...

Primary and secondary prevention of cardiovascular disease is of utmost importance in the management of patients with diabetes.We studied a group of Iranian patients with type2 diabetes to provide an overview of the current status of secondary prevention of cardiovascular disease in the Middle East.This is a cross-sectional study of 2029 Patients with type2 diabetes including 323 patients with coronary artery disease (CAD) were recruited. Achievement of goals in HbA1c (A), blood pressure (B) and LDL-cholesterol(C) was assessed.The study showed 25.3% of CAD positive patients achieved HbA1c7% compared to 30% in CAD negative patients. The achievement of blood pressure ≤140/90 mmHg was 53.2% and 52.8% in CAD positive and CAD negative patients respectively. There was no difference in the achievement of all three ABC goals between the two groups (p = 0.733). After logistic regression analysis, history of hypertension had the highest odds ratio for CAD.Although ABC control has an important impact on the prevention of cardiovascular outcomes, the ideal goal needs further efforts to be achieved. more...

The role of chronic inflammation and oxidative stress in the development of diabetes and cancer has been established. In this study, we aimed to investigate inflammatory and oxidative stress markers in patients with diabetes (DM) and endometrial carcinoma (EC) separately and in combination.In a case-control study design, a total of 88 participants were enrolled including: 37 patients with EC (19 with DM and 18 without DM), 29 with type2 diabetes and 22 healthy controls. Cancer patients were sampled before treatment. Serum oxidative stress markers including: oxidized low density lipoprotein (ox-LDL,) nitric oxide (NO), advanced glycation end-products (AGEs) and advanced oxidation protein products (AOPP), malondialdehyde (MDA); ferric reducing ability of plasma (FRAP), as an antioxidant marker, and inflammatory markers including: Interleukin 6 (IL6), C reactive protein (CRP) and tumor necrosis factor alpha (TNFα) were measured.Ox-LDL, NO, MDA, AOPP and AGE were increased in all patients either with endometrial carcinoma and/or diabetes compared to healthy controls (p 0.05). Patients with both EC and DM had higher oxidative markers including: OX-LDL (17.47 ± 0.84 vs. 12.36 ± 0.91), NO (82.27 ± 5.75 vs. 76.34 ± 5.36), MDA (3.3 ± 0.1 vs. 2.75 ± 0.48) and AGE (73.89 ± 5.71 vs. 69.02 ± 3.14) compared to those with EC alone (ρ 0.05). Levels of FRAP was lower in patients with both diabetes and cancer, cancer alone and diabetes alone compared to healthy controls (p 0.05). Inflammatory markers, TNFα, IL6 and hs-CRP, were also significantly increased in patients with EC with and without DM compared to controls (ρ 0.05). However, there were no significant differences between two groups of EC regarding to inflammatory markers (ρ 0.05). Patients with DM had significantly higher levels of inflammatory markers compared to control group (all ρ 0.05). In addition, significant subadditive interaction effect between EC and DM regarding levels of oxLDL, NO, AGE, AOPP and FRAP) was observed (p 0.05).Increased levels of chronic inflammatory and oxidative stress markers were observed in both endometrial carcinoma and diabetes. Additional effect of diabetes in patients with cancer was mediated more significantly via increase in oxidative stress rather than inflammatory markers. more...

Backgrounds : Metabolic syndrome can facilitate the development of diabetes mellitus and has gained a negative reputation for its adverse effects on the general health of the population and its tendency to increase the risk of cardiovascular diseases. Cardiovascular complications may be mediated by the alteration of certain enzyme activities and pathways. Lecithin-Cholesterol Acyltransferase (LCAT) may have a potential role in the prevention of atherosclerosis as a rate-limiting enzyme in reverse cholesterol transport. In this study, LCAT activity was compared among patients with type 2 diabetes in the presence or absence of metabolic syndrome. Methods : In the present study, 55 patients with type 2 diabetes with metabolic syndrome (DM+MS group), 25 patients with type 2 diabetes without metabolic syndrome (DM-MS group), and a control group of 43 subjects without type 2 diabetes (HC group) were compared based on their anthropometric parameters, lipid profiles, glycemic indices, and LCAT activity. Results: LCAT activity was lower among participants of the DM+MS group (70.22±7.88) in comparison with the both HC group (89.51±3.59) and the DM-MS group (76.73±7.25) (respectively P more...

Despite few studies on intracellular heat shock protein70, the clinical association between insulin resistance and extracellular heat shock protein70 (eHSP70) is not well studied. In the current study, we examined the association between homeostatic model assessment-insulin resistance (HOMA-IR) and eHSP70 in patients with type 2 diabetes (T2DM) and healthy controls. A total of 145 patients with T2DM and 41 matched healthy controls were selected. Patients and controls were divided based on waist circumference (WC) to two groups, and eHSP70 was compared between them. The association between HOMA-IR and eHSP70 was examined using regression models adjusted for age, high-sensitive C-reactive protein (hs-CRP), and central obesity as confounding factors. While eHSP70 and hs-CRP were significantly correlated with HOMA-IR in patients with T2DM (p = 0.032, 0.025, respectively), there was no correlation between eHSP70 and HOMA-IR in the control group. Extracellular HSP70 and hs-CRP were not correlated in healthy controls. But a significant association appeared between eHSP70 and hs-CRP in patients with T2DM (p = 0.05). Both BMI and WC were not correlated with eHSP70 in both groups. Extracellular HSP70 was positively associated with HOMA-IR in patients with T2DM, independent from hs-CRP and obesity. We also showed eHSP70 levels remained unchanged through increase in BMI or WC in patients with T2D and in healthy controls. Our findings suggest that eHSP70 may contribute to the pathogenesis of T2DM by increasing insulin resistance. more...

Context Most recently developed anti-hyperglycemic drugs have offered cardiovascular and renal benefits. In this narrative review, we discuss the cardiovascular and renal benefits of novel antidiabetic drugs, sodium glucose cotransporter type 2 (SGLT2) inhibitors, in type 2 diabetes. Evidence acquisition The literature published in PubMed, Scopus, Web of Science, Google Scholar, and Cochrane library were reviewed up to January 2019. The keywords including SGLT2 inhibitor, type 2 diabetes, cardiovascular effect, and renal effect were used in different combinations. Results Cardiovascular disease represents a large health burden in patients with diabetes. The prevention of cardiovascular events is a major concern in the treatment of patients with diabetes. Diabetes is also associated with an increased risk of adverse renal events and diabetic nephropathy is the leading cause of end-stage renal disease worldwide. SGLT2 inhibitors as new glucose-lowering agents act by inhibiting glucose reabsorption in the proximal tubule of the kidney, which is independent of insulin secretion. We reviewed the cardiovascular effects of these drugs including effects on triple MACE (major adverse cardiovascular events), myocardial infarction, heart failure, cardiovascular and all-cause mortality, and stroke, as well as renal effects including albuminuria, serum creatinine, the rate of renal replacement therapy, and renal function over time, along with the mechanisms of these effects. Conclusions Given the suboptimal glycemic and cardiovascular risk control in type 2 diabetes, novel therapies such as SGLT2 inhibitors seem to have an important clinical advantage to improve glycemic control and cardiovascular and renal outcomes. more...

Background Vitamin D deficiency is proposed as a risk factor for coronary heart disease (CHD). An inverse relation was observed between serum 25-Hydroxy-Vitamin-D level and incidence of hypertension. This study aimed to evaluate the predictive value of serum 25-Hydroxy-Vitamin-D in improvement of CHD risk-stratification in patients with hypertension. Methods In this cohort, we followed 1586 patients with essential hypertension (1078 diabetic and 508 non-diabetic) for 8.5 years. Physician-adjudicated first hard CHD event was the primary outcome. Cox regression analysis was used to investigate the association between 25-Hydroxy-Vitamin-D quartiles and incident CHD. 25-Hydroxy-Vitamin-D was also added to the Framingham Risk Score (FRS) and Net-Reclassification-Improvement (NRI) and Integrated-Discriminant-Improvement (IDI) were used to examine improved reclassification. Results During follow-up, 176 events were recorded. Patients in the lowest quartile of 25-Hydroxy-Vitamin-D experienced the most number of hard CHD events. A significant linear trend was observed in hazard ratios (HR) of incident hard CHD events in 25-Hydroxy-Vitamin-D quartiles which remained significant after multiple adjustments for conventional CHD risk-factors (HRs in full-adjusted model: 2.87 [1.76–4.70] for 1st quartile, 2.31 [1.39–3.83] for 2nd quartile and 1.87 [1.15–3.03] for 3rd quartile, compared with the highest quartile; p-for-trend Conclusion We observed that serum 25-Hydroxy-Vitamin-D is independently associated with future hard CHD events and improves its prediction in patients with essential hypertension. Addition of serum 25-Hydroxy-Vitamin-D to CHD risk-estimation models may have additive values. more...

Aims Fetuin-A is a circulating glycoprotein capable of inhibiting insulin signaling both in vivo and in vitro and is positively associated with insulin resistance. Osteoprotegerin (OPG) acts as a regulatory molecule with increased levels in the early stages of diabetes and atherosclerosis, and is also associated with insulin resistance. We investigated the effects of pioglitazone and metformin as representative insulin-sensitizing therapies on fetuin-A and OPG levels. Materials and methods In a randomized clinical trial setting ( NCT02027103 ), 88 patients with newly diagnosed type 2 diabetes were randomly assigned to pioglitazone (30 mg/day, n = 46) or metformin (1000 mg/day, n = 42) for 12 weeks. Various anthropometric and metabolic parameters, fetuin-A, OPG, highly sensitive C-reactive protein (hsCRP), and homeostasis model assessment of insulin resistance (HOMA-IR) were measured at baseline and after three months. Results The reduction in fasting plasma glucose and haemoglobin A1c levels was comparable in the two arms. Pioglitazone resulted in a significant reduction in both fetuin-A and OPG in men, but only fetuin-A in women. Metformin was only effective in lowering OPG levels in women. When compared, both medications were equally effective with regard to fetuin-A and OPG reduction in women ( p = 0.413 and 0.359, respectively). In men, pioglitazone more effectively decreased fetuin-A levels in both uni- ( p = 0.011) and multivariate models ( p = 0.015) and OPG levels in only uni- ( p = 0.023) but not the multivariate model ( p = 0.547). Conclusions Metformin and pioglitazone differentially affect fetuin-A and osteoprotegrin levels in diabetic women and men. The level of change may not necessarily be associated with the amelioration of insulin resistance. more...

Background Osteoprotegerin plays a critical role in the pathogenesis of atherosclerosis. Elevated osteoprotegerin concentrations have been reported in microvascular complications of diabetes. Patients with diabetes are at increased risk of macrovascular complications, particularly peripheral artery disease (PAD). Aim To investigate the association between osteoprotegerin concentration and PAD in diabetes. Methods In a cross-sectional setting, patients with type 2 diabetes for > 5 years and no apparent diabetic foot ulcer were recruited. Patients underwent colour Doppler ultrasonography of lower limbs and were designated PAD+ if arterial narrowing was detected. Ankle-brachial index (ABI) was measured. Serum osteoprotegerin concentrations were determined. Results Ninety-eight patients (47 PAD+, 51 PAD–) were recruited. Osteoprotegerin concentrations (median [interquartile range]) were significantly higher in PAD+ versus PAD– patients (0.80 [0.50–1.95] ng/mL vs 0.30 [0.25–0.40] ng/mL; P more...

Patients with diabetes have higher stress-to-rest mean left ventricular volume (SRLVV) ratio in myocardial perfusion imaging (MPI) and hyperhomocysteinemia. We studied the effect of folate therapy on SRLVV ratio and plasma homocysteine levels in patients with diabetes. Forty patients were enrolled and thirty-two completed the study. The patients underwent a 2-day pharmacological stress test and rest MPI before and 2 months after treatment with either 5 mg folic acid or placebo. SRLVV ratios were calculated, and plasma homocysteine levels were measured, before and after treatment. Among the 32 patients who completed the study, 15 received folic acid and 17 received placebo. The age of subjects (folate 51.5 ± 6.1 years; placebo 50.6 ± 8.1 years), male/female ratio (folate 6/11; placebo 9/6),or MPI findings (proportion of normal results: folate 80.0 %; placebo 94.1 %) were similar between the two groups. The baseline SRLVV ratio was similar between groups (folate: 1.00 ± 0.09 vs. placebo: 0.97 ± 0.13); however, the post-treatment SRLVV ratio was significantly lower (P more...

Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) are dysregulated in metabolic syndrome (MetS) and associated with atherosclerosis and cardiovascular disease (CVD). Previous studies on the association between MMPs/TIMPs and MetS are controversial. We aimed to evaluate circulating MMP-8, MMP-9 and TIMP-1 in a group of MetS individuals and healthy controls to find the potential marker associated with MetS and its components.243 MetS individuals participated in a nested case-control design, of whom 63 were excluded (study subjects for analysis n=180; 87 MetS cases, 93 controls). We employed the International Diabetes Federation criteria using national waist circumference cutoffs for case definition. Anthropometric and biochemical measurements were done using standard methods.Plasma MMP-8, TIMP-1, tumor necrosis factor-alpha (TNF-α), highly sensitive C-reactive protein (hs-CRP) and MMP-8/TIMP-1 ratio were significantly higher in MetS cases (P for all0.05). Each component of MetS except raised fasting plasma glucose positively correlated with MMP-8 and numbers of MetS components increased with higher MMP-8. In all regression models, MMP-8 was a significant predictor of MetS and in the final model the relationship persisted even after adjusting for pro-inflammatory cytokines hs-CRP and TNF-α (odds ratio=6.008, 95% confidence interval: 1.612-22.389, P=0.008).Strong associations of MMP-8 with components of MetS in univariate, bivariate and multivariate models suggest plasma MMP-8 as a potential cardiometabolic risk marker for MetS. Higher MMP-8 in MetS is possibly mediated through mechanisms both dependent and independent of chronic low grade inflammation. more...

Background/Aims: This prospective study is aimed at examining the predictive value of high-sensitivity C-reactive protein (hs-CRP) for coronary heart disease (CHD) events and microvascular complications of type 2 diabetes mellitus (T2DM). Methods: A population-based study (NCT02958579) was conducted on 1,301 participants with T2DM (mean follow-up of 7.5 years). Risk assessment for vascular events was done at baseline, and serum hs-CRP was measured. End points of this study include CHD events, diabetic retinopathy, neuropathy, and diabetic kidney disease. Individuals with unavailable data or hs-CRP >20 mg/L were excluded. The discrimination and reclassification improvement of study end points were tested after addition of hs-CRP to traditional risk factors. Results: Median serum hs-CRP was 2.00 ranging from 0.1 to 17 mg/L. Hazards ratio of each SD increment in baseline hs-CRP was 1.028 (1.024–1.032) for CHD, 1.025 (1.021–1.029) for diabetic neuropathy, 1.037 (1.030–1.043) for diabetic retinopathy, and 1.035 (1.027–1.043) for diabetic kidney disease. The addition of hs-CRP to traditional risk factors of vascular complications of T2DM improved discrimination of all end points (p < 0.001). Net reclassification improvement ranged from 8% for diabetic neuropathy to 31% for diabetic kidney disease (p < 0.05). Conclusion: Baseline hs-CRP predicts both of CHD events and microvascular complications of patients with T2D. more...

Background: Coronary heart disease (CHD) is one of the most common causes of mortality worldwide. The national prevalence remains unclear in most of the developing countries. Objective: This study sought to estimate national prevalence of self-reported CHD and chronic stable angina pectoris in the general adult population of Iran using data from the fourth round of the Surveillance of Risk Factors of Non-Communicable Diseases (SuRFNCD-2011) survey. Methods: The analysis comprised data of 11,867 civilian, nonhospitalized and noninstitutionalized residents ages 6 to 70 years of age. The calculated prevalence of self-reported CHD and chronic stable angina pectoris were extrapolated to the Iranian adult population who were >20 years old using the complex sample analysis. The factor analysis was performed for clustering of the associated cardiometabolic risk factors among people ages >40 years of age. Results: The estimated national prevalence of self-reported CHD and chronic stable angina pectoris were 5.3% (95% confidence interval: 4.6 to 5.9) and 7.7% (95% confidence interval: 4.6 to 8.7), respectively. Higher prevalence of these conditions were observed among the older people, urban residents, and women. Factor analysis generated 4 distinct factors that were mainly indicators of dyslipidemia, hypertension, central obesity, hyperglycemia, and tobacco smoking. The factor incorporating hypertension was a significant correlate of selfreported CHD. Conclusions: We report concerning prevalence of self-reported CHD and chronic stable angina pectoris in the adult population of Iran. The constellation of raised systolic and diastolic blood pressures was significantly predictive of the presence of self-reported CHD. Highlights The prevalence of self-reported CHD and chronic stable angina pectoris was determined in the adult population of Iran in 2011. The estimated national prevalence of self-reported CHD was calculated at 5.3% (95% CI: 4.6 to 5.9). The estimated national prevalence of chronic stable angina pectoris was calculated at 7.7% (95% CI: 4.6 to 8.7). Hypertension was an independent correlate of self-reported CHD and chronic angina pectoris among Iranian adult population. Monitoring people with raised SBP and DBP should be the focus of future nationwide CHD prevention programs. more...