Impact of pomegranate juice on blood pressure: A systematic review and meta-analysis.

Despite the importance of polyphenol-rich fruits in decreasing cardiovascular mortality, the impact of pomegranate juice (PJ) on blood pressure is still unclear. To determine the effect of PJ on blood pressure. PubMed, Scopus, ISI Web of Science, and Cochrane Library were searched comprehensively using relevant keywords. All studies using pomegranate juice alone were included although limited to human studies and the English language. A random-effects model and the generic inverse variance approach were used to determine quantitative data synthesis. Meta-analysis of 14 clinical trials (n = 573 individuals) demonstrated a reduction in systolic BP (SBP) with pomegranate juice (MD: -5.02 mmHg, 95% CI: -7.55 to -2.48, p < 0.001). Effect of study duration showed pomegranate juice intake ≤2 months significantly decreased SBP (MD: -4.59 mmHg, 95% CI: -7.10 to -2.08, p < 0.001) and DBP (MD: -2.94 mmHg, 95% CI: -5.25 to -0.63, p = 0.01). Consumption of ≤300 mL pomegranate juice daily reduced SBP (MD: -6.11 mmHg, 95% CI: -9.22 to -3.00, p < 0.001). Counterintuitively, >300 mL/day of pomegranate juice showed no effect on SBP (MD: -3.28 mmHg, 95% CI: -6.85 to 0.27, p = 0.07) but a significant DBP reduction occurred (MD: -3.10 mmHg, 95% CI: -5.74 to -0.47, p = 0.02). Meta-regression showed that the SBP-lowering effect of pomegranate juice was associated with the dose of supplementation (p < 0.001). Pomegranate juice appeared to decrease SBP and DBP in a dose-dependent manner, but the benefit was lost after 2 months of pomegranate juice intake.

Hsp70, in Combination with IL-15 and PD-1 Blocker, Interferes with The Induction of Cytotoxic NK Cells in Relapsed Acute Myeloid Leukemia Patients.

OBJECTIVE: Natural killer (NK) cells are critical immune cells for acute myeloid leukemia (AML) targeting. However, little is known about the relationship between using checkpoint inhibitors and heat shock protein 70 (Hsp70) as NK cell activators to control AML. Therefore, the study aims to find the best formulation of Hsp70, human PD-1 (Programmed cell death protein 1) blocker, and interleukin 15 (IL-15) to activate NK cells against AML. MATERIALS AND METHODS: In this experimental study, the NK cells were isolated from mononuclear cells (MNCs) by using magnetic activation cell sorting (MACS) and were activated using the different combinations of Hsp70, PD-1 blocker, and IL-15 and then followed by immunophenotyping, functional assays to estimate their killing potential, and evaluation of expression pattern of PRF1, PIK3CB, PD-1, AKT-1, FAS-L, TRAIL, and GER A and B. RESULTS: The expression of PD-1 was significantly (P<0.05) reduced after NK cell activation by the different formulas of IL-15, Hsp70, and PD-1 blocker. The expression of NKG2A in the treated NK cells was reduced particularly in the IL-15 (P<0.01) and IL-15+PD-1 blocker (P<0.05) groups. The addition of Hsp70 increased its expression. The cytotoxic effect of NK cells increased in all groups, especially in IL-15+PD-1 blocker besides increasing interferon-gamma (IFN-γ), Granzymes, and perforin expression (P<0.05). All IL-15+PD-1 blocker group changes were associated with the upregulation of PIK3CB and AKT-1 as key factors of NK cell activation. The presence of Hsp70 reduced IFN-γ releasing, and down-regulation of PIK3CB, AKT-1, Granzymes, and Perforin (P<0.05). CONCLUSION: We suggested the combination of IL-15 and PD-1 blocker could enhance the killing potential of AMLNK cells. Moreover, Hsp70 in combination with IL-15 and PD-1 blocker interferes activation of AML-NK cells through unknown mechanisms.

The Efficacy of Ginseng (Panax) on Human Prediabetes and Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis.

Results from different clinical trials on the effects of ginseng on prediabetes and type 2 diabetes (T2DM) are still inconsistent. To fill this knowledge gap, we investigated the overall effects of ginseng supplementation on improving cardiometabolic biomarkers among these patients. A systematic literature search was conducted on PubMed/MEDLINE, Scopus, Web of Science, and Cochrane library. A random-effect model was applied to estimate the weighted mean difference and 95% CI for each outcome. Overall, 20 eligible RCTs were included. Meta-analyses revealed that ginseng supplementation significantly reduced serum concentration of FPG, TC, IL-6, and HOMA-IR values. It also increased HR and TNF-α levels. Ginseng supplementation changed HOMA-IR and HDL-C significantly based on dose and changed HOMA-IR and LDL-C significantly based on study duration in a non-linear fashion. Furthermore, meta-regression analyses indicated a linear relationship between ginseng dose and absolute changes in HDL-C. Moreover, subgroup analyses showed that ginseng supplementation changed TC and LDL-C when the supplementation dose was ≥2 g/day. Our findings suggest that ginseng supplementation may be an effective strategy for improving cardiometabolic profiles in individuals with prediabetes and T2DM.

Obesity and Diabetic Complications: A Study from the Nationwide Diabetes Report of the National Program for Prevention and Control of Diabetes (NPPCD-2021) Implications for Action on Multiple Scales.

BACKGROUND: 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. METHODS: 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. RESULTS: 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 and <0.001, 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-values <0.001). CONCLUSION: 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.

COVID-19 infection mortality risk in Iranian patients with type 2 diabetes, hypertension and obesity.

Background: Diabetes mellitus and hypertension are highly prevalent among patients with severe COVID-19. Aims: 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. Methods: 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. Results: 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, P < 0.001]. 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, P < 0.001). The odds ratio of the risk of mortality in patients with diabetes, hypertension and obesity was 1.87 (95% CI: 1.35-2.58, P < 0.001). Conclusion: 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.

Policy Implications for Diabetes Prevention and Control: An Experience from Iran.

Background: Diabetes and its complications threaten the life of communities at global, national, and sub-national levels. Following the United Nations' call to action and develop a global action plan for the prevention and control of NCDs by The World Health Organization (WHO), all countries have a commitment to halt the rise in diabetes prevalence across the world. But the different situations of disease and risk factors, different priorities, and the context of the health care systems moved the countries to develop adapted targets and action plans. On the same ground, Iran established a national authority construction as the Diabetes Sub-committee which is part of the Iranian Non-Communicable Diseases Committee (INCDC) and incorporated a multi-sectoral mechanism to develop the national service framework for diabetes. Accordingly, this paper is aiming at sharing Iran's experience regarding the policy implications for diabetes prevention and control. Exchange this experience could be beneficiary to other countries to lead a systematic action to prevent disability and mortality due to diabetes.

Effects of a Mediterranean diet on the development of diabetic complications: A longitudinal study from the nationwide diabetes report of the National Program for Prevention and Control of Diabetes (NPPCD 2016-2020).

OBJECTIVE: 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. METHODS: 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. RESULTS: 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-value <0.001 and OR= 0.61, 95% CI: 0.57 - 0.89, p-value <0.001, respectively). Also, the diet had a statistically significant protective effect against incident symptomatic neuropathy (OR= 0.32, 95% CI: 0.23 - 0.43, p-value <0.001, and OR= 0.68, 95% CI: 0.64 - 0.72, p-value <0.001, respectively), nephropathy (OR= 0.42, 95% CI: 0.30 - 0.58, p-value <0.001, 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-value <0.001, and OR= 0.68, 95% CI: 0.61 - 0.71, p-value <0.001, respectively) in T1D and T2D. CONCLUSION: 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.

Smoking and Diabetes Control in Adults With Type 1 and Type 2 Diabetes: A Nationwide Study From the 2018 National Program for Prevention and Control of Diabetes of Iran.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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 values <0.001). Among patients with type 1 diabetes, smoking was significantly (p<0.05) 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). CONCLUSIONS: 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.

Determinants of glycemic control: Phase 2 analysis from nationwide diabetes report of National Program for Prevention and Control of Diabetes (NPPCD-2018).

BACKGROUND: Diabetes is one of the leading causes of morbidity and mortality worldwide, especially among middle and low income nations. Many diabetic complications and comorbidities are attributable to poor glycemic control. The aim of this study was to update and extend the national diabetes reports on the status of comorbidities, diabetes care and complications in Iran. Moreover, we investigated the risk factors of poor glycemic control in the Iranian population. METHODS: National database of 99,651 patients with diabetes who attended university-affiliated clinics between April 1, 2017 and February 30, 2018 was used to carry out a cross-sectional study. Stepwise backward selection logistic regression model was used to examine the associated factors of glycemic control. RESULTS: In this study 73.0% and 56.5% of the enrolled population with diabetes, had hypertension and hyperlipidemia, respectively. The prevalence of patients who received education for nutrition therapy or diabetes self-management was 16.3% and 23.3% respectively. Poor glycemic control was associated with male gender (OR=1.06, p=0.001), obesity (OR=1.03, p=0.05), duration of diabetes (OR=1.018, p<0.001), smoking (OR=1.08, p=0.041), hypertension (OR=1.53, p<0.001), hyperlipidemia (OR=1.15, p<0.001), insulin therapy (OR=1.26, p<0.001) and combination of insulin and oral anti-diabetic agents compared to oral anti-diabetic agents alone (OR=2.36, p<0.001). CONCLUSION: We demonstrated that the prevalence of diabetes comorbidities is high in Iranian population and that a great proportion of Iranian patients with diabetes had not reached the goal of glycemic control. Our findings provide a starting point from which to investigate the obstacles that prevent patients with diabetes from reaching metabolic targets.

Association of non-alcoholic fatty liver disease with microvascular complications of type 2 diabetes.

INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) affects risks of type 2 diabetes (T2D), diabetes-related complications, and cardiovascular disease in a complex manner. This study is designed to clarify associations of sonographically-detected NAFLD and serum liver enzymes with diabetes-related microvascular complications. METHODS: A matched case-contorl study was designed for 440 patients with T2D and at least one of the chronic diabetes-related microvascular complications and 495 age- and gender-matched control patients with T2D. RESULTS: Considering pre-existing and newly developed chronic microvascular complications, diabetic peripheral neuropathy was found in 347 out of 935 (37.1%) study patients, diabetic retinopathy in 141/935 (15.1%), and diabetic nephropathy in 103/935 (11.0%). Diagnosis of diabetic retinopathy and diabetic nephropathy were inversely associated with the presence of NAFLD in the crude logistic regressions (OR [95% CI] = 0.18 [0.05-0.63], p value = 0.007; OR [95% CI] = 0.17 [0.04-0.59], p value = 0.011, respectively). The subgroup of NAFLD with elevated liver enzymes had lower odds of having diabetic peripheral neuropathy in the fully adjusted model (OR [95% CI] = 0.34 [0.12-0.98], p value = 0.048). CONCLUSION: Diagnosis of NAFLD with or without elevated serum liver enzymes was inversely correlated with certain chronic diabetes microvascular complications. Possible explanations for this counter-intuitive and unexpected finding are discussed and center on reverse-causality, wherein sicker patients may develop beneficial compensatory physiological and behavioral adaptations. Diversity of studied patients, in particular with regards to the ethnic and racial differences among the Western and Asian populations may also partly account for contrasting findings of the relationship between NAFLD and microvascular complications of diabetes.

Diabetes in Iran: Prospective Analysis from First Nationwide Diabetes Report of National Program for Prevention and Control of Diabetes (NPPCD-2016).

We estimated proportions of different types of diabetes, comorbidities, treatment (the use of oral glucose-lowering agents and insulin), control (hyperglycemia, dyslipidemia and hypertension) and chronic microvascular and macrovascular complications among people with diabetes presenting to the tertiary-care academic diabetes outpatient clinics in Iran. This study is the prospective analysis of data (n = 30,202) from the registry of university-affiliated adult outpatient diabetes clinics in the country during 2015-2016. The proportions of type 1 diabetes, types 2 diabetes, and other types of diabetes were 11.4%, 85.5%, and 1.3%, respectively. The frequencies of drug-naivety, use of oral agents, insulin monotherapy and insulin combination therapy were 2.9%, 60.5%, 11.5%, and 25.1%, respectively. Around 13.2%, 11.9% and 43.3% of patients with diabetes had controlled hyperglycemia, hyperlipidemia and hypertension, respectively. The proportions of retinopathy, nephropathy, peripheral neuropathy, diabetic foot, and ischemic heart disease were 21.9%, 17.6%, 28.0%, 6.2%, and 23.9%, respectively. Despite the wide availability of medications and insulin coverage in Iran, the estimated national control of hyperglycemia, hyperlipidemia and hypertension (especially for young men and old women) remains subpar. The present study further suggests that the frequencies of chronic vascular complications among patients with diabetes are relatively high in Iran.

Outlook of organ transplantation in Iran: time for quality assessment.

Organ transplantation as an undeniable life-saving therapeutic modality fundamentally requires infrastructure, devoted and trained professionals, and positive public attitude to be set up in a well-organized manner at the national level. In addition to sharing achievements and reviewing the increasing trend of transplanted organs in the past 12 years following legislations in Iran, this report raises some concerns from the point of transplantation outcome view.

Short-term survival in renal transplantation from brain-death donors: focusing on recipients with diabetes background.

PURPOSE: Our aim was to evaluate short term survival rates in renal transplant recipients from deceased donors, while focusing on recipients with diabetes mellitus background. MATERIALS AND METHODS: This is a longitudinal follow-up study based on national registry of recipients in Ministry of Health and Medical Education in Iran from 2010-11. Five hundred fifty-five recipients, 226 (40.8%) females and 328 (59.2%) males, were included in the study. Mean (± SD) age of the recipients was 39 ± 14 years. Of donors 18.4% were females and 81.6% were males. Age of the donors was 33 ± 14 years. All allograft recipients from deceased donors enrolled in the study. Short-term graft survival (1 year) was determined. Data regarding age, gender, background disease and cold ischemic time of recipients and donors were collected from the organ procurement units. RESULTS: Allografts were functioning in 499 (90.1%) of recipients after one year. Of recipients 38 (6.9%) died and rejection of transplanted kidney occurred in 17 (3.1%) cases. So, in 55 (9.9%) cases, allografts were not functioning. There were significant relationships between short term graft survival of donors' gender, age of recipients, cold ischemic time and level of clearance of creatinine of recipients. CONCLUSION: In addition to cold ischemic time, graft survival can be affected by recipients' age. There are some other considerations and implications regarding the short term graft survival in renal transplantation from cadaver donors which are discussed in this paper.

Survival rate in lung, liver, heart and pancreas transplant recipients in iran: a registry-based study.

BACKGROUND: The main purpose of organ transplantation is to prolong and maintain a quality life for patients with organ dysfunction. OBJECTIVE: We tried to evaluate short-term survival rates in lung, liver, heart and pancreas recipients. METHODS: This longitudinal study was based on the data of national registry of recipients in Ministry of Health and Medical Education (MOHME), Iran. Survival rate after 1 year of transplantation, recipients' age, gender, ischemic time as well as the number of transplantation units, OP units and identification units were collected from the database for all transplantation done between 2010 and 2011. RESULTS: 407 (223 female, and 184 male) patients were enrolled in the study. 13 (3.2%) patients received lung, 299 (73.5%) liver, 85 (20.9%) heart and 10 (2.5%) received pancreas. Within 1 year of transplantation, 61.5% of lung recipients, 88.3% of liver recipients, 72.9% of heart recipients and 80% of pancreas recipients (overall 85.3%) were functioning. CONCLUSION: Given the short history of transplantation in Iran, we have achieved great success.