Theobromine supplementation in combination with a low-calorie diet improves cardiovascular risk factors in overweight and obese subjects with metabolic syndrome: a randomized controlled trial.

Background & aims: The beneficial effects of theobromine (TB) on obesity and features of metabolic syndrome (MetS) have been reported in several studies. However, the findings are equivocal. The present study aimed to investigate the effects of 12 week pure TB supplementation (450 mg day-1) combined with a low-calorie diet on the anthropometric and metabolic syndrome indices in overweight and obese adults with MetS. Methods: In a randomized double-blind parallel controlled trial, 80 participants aged 40-55 years were randomly assigned to take 450 mg day-1 TB or placebo along with a low-calorie diet for 12 weeks. Dietary intake, anthropometric indices, blood pressure, lipid profile and glycemic indices were assessed at the start and end of the intervention. Results: Seventy-two participants completed the study. After 12 weeks, TB supplementation significantly decreased the waist circumference (WC) (-0.86 cm; P = 0.045), LDL-c/HDL-c (-0.26; P = 0.008), TG/HDL-c (-0.41; P = 0.001), TC/HDL-c (-0.38; P = 0.006) and increased HDL-c (1.72 mg dl-1; P = 0.036) compared to the placebo group. There were no significant differences regarding body weight, BMI, hip circumference (HC), hip-to-waist circumference ratio (WHR), systolic and diastolic blood pressure, fasting levels of total cholesterol (TC), triacylglycerol (TAG), low-density lipoprotein cholesterol (LDL-c), fasting blood glucose, insulin, homoeostatic model assessment for insulin resistance (HOMA-IR) and homeostasis model assessment of ß-cell function (HOMA-ß) between the two groups (p > 0.05). Conclusion: The results of the current study revealed that TB supplementation along with a low-calorie diet had favorable effects on WC, LDL-c/HDL-c, TG/HDL-c, TC/HDL-c, and serum level of HDL-c in overweight and obese subjects with MetS. Trial registration number: IRCT20091114002709N59. Registration date: 5 March 2022.

Oxidative stress parameters and keap 1 variants in T2DM: Association with T2DM, diabetic neuropathy, diabetic retinopathy, and obesity.

INTRODUCTION: Chronic hyperglycemia activates the inflammatory pathways and oxidative stress mechanisms with consequent damage to nerve tissue and retina. The Keap1-Nrf2 pathway acts as one of the most important antioxidant pathways of the organism. Variants of Keap1 could affect susceptibility to diabetes and its complications. METHODS: In a case-control study, 400 individuals included type 2 diabetes mellitus (T2DM) patients without complication, with neuropathy, with retinopathy, and healthy individuals were investigated. The levels of glutathione (GSH), glutathione peroxidase (GPx), malondialdehyde (MDA), and total antioxidant capacity (TAC) were measured using chemical methods. Using the PCR-RFLP method, the Keap1 (rs11085735) variants were identified. RESULTS: Neuropathic patients had significantly lower levels of GSH, GPx, and TAC and higher levels of total oxidative status (TOS), MDA, and oxidative stress index (OSI) compared to T2DM patients without complication and controls. Lower levels of GSH and GPx and a higher level of MDA were observed in patients with retinopathy compared with controls. Obesity was associated with significantly lower GPx activity and higher TOS. A significantly higher Keap1 AA genotype was found in patients with neuropathy than T2DM without complication and controls. The presence of Keap1 AA genotype correlated with lower GPx activity compared to CC genotype. CONCLUSIONS: Our study suggests the role of reduced antioxidant system and Keap1 variants in the pathogenesis of T2DM and its complications of neuropathy and retinopathy and also obesity in enhanced oxidative stress. Monitoring oxidative stress parameters in diabetic patients, especially those with complication and their treatment with antioxidants is suggested.

Comparison of sirtuin 1 level and related blood factors in diabetic and healthy subjects.

INTRODUCTION: Diabetes (II) is a chronic metabolic disease with many side effects. Sirtuin 1 (SIRT1) regulates prominent cellular processes such as apoptosis, aging, and metabolism of the cell, and it seems to play an important role in type 2 diabetes. THE AIM OF THE STUDY: was to compare the serum level of SIRT1 and related biochemical factors in patients with controlled and uncontrolled diabetes with healthy subjects. METHODS: Type 2 diabetic patients were randomly divided into controlled and uncontrolled fasting blood glucose (FBG) and healthy individuals as the control group (n = 50/group). Serum levels of SIRT1, haemoglobin A1C (HbA1c), low-density lipoprotein (LDL), high-density lipo-protein (HDL), triglyceride (TG), FBG, and body mass index (BMI) were evaluated. RESULTS: The mean ±SD level of SIRT1 in the uncontrolled diabetic group (3.96 ±2.52) was significantly (p < 0.001) lower than that of the con-trolled diabetic (9.22 ±4.11) and healthy subjects (10.65 ±2.2). The levels of HbA1c, FBG, LDL, HDL, and TG indicated significant differences between the groups (p < 0.05). There was a significant reverse correlation between SIRT1 with HbA1c, FBG, age, and BMI (p < 0.05) and a positive significant correlation between BMI and HbA1c (p = 0.007). CONCLUSIONS: Sirtuin 1 is associated with improving glucose homeostasis. Therefore, it can be considered as a new therapeutic target for prevention and treatment of type 2 diabetes.

The Insulin-like Growth Factor-1 (G>A) and 5,10-methylenetetrahydrofolate Reductase (C677T) Gene Variants and the Serum Levels of Insulin-like Growth Factor-1, Insulin, and Homeostasis Model Assessment in Patients with Acne Vulgaris.

BACKGROUND & OBJECTIVE: To find an association between gene variants of insulin-like growth factor-1 (IGF-1) and 5,10-methylenetetrahydrofolate reductase (MTHFR) with the risk of acne vulgaris (AV). METHODS: In a case-control study, we investigated 150 AV patients and 148 healthy individuals (aged 18-25 years) for the IGF-1 G>A and MTHFR C677T polymorphisms, as well as the serum levels of IGF-1, insulin, and the homeostasis model assessment of insulin resistance (HOMA-IR). The serum biochemical parameters and the genotypes of IGF-1 G>A and MTHFR C677T were detected by using appropriate kits and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods, respectively. RESULTS: The frequencies of IGF-1 and the MTHFR polymorphisms were not significantly different comparing patients and controls. The serum level of IGF-1 was 179.8±72.8 µg/L in AV patients compared to 164.6±63.7 µg/L in controls (P=0.056). The serum level of insulin in female patients was significantly higher than controls. The HOMA was 3.54±5.6 in patients compared to 1.16±1.4 (P<0.001) in controls. Significantly higher levels of fasting blood sugar (FBS), total cholesterol, and low-density lipoprotein-cholesterol (LDL-C) were detected in female patients than controls. However, the level of estradiol was significantly lower in female patients than in controls. In females, the presence of the MTHFR T allele was associated with significantly higher levels of FBS and LDL-C, as well as a significantly lower level of estradiol compared to those carriers of the C allele. CONCLUSION: We found the absence of an association between IGF-1 and MTHFR polymorphisms with the risk of AV. However, increased insulin, IGF-1, and HOMA levels in AV patients indicated the effect of insulin and insulin resistance in the risk of AV and its severity.

Characterization and anti-diabetic effects of the oligosaccharide fraction isolated from Rosa canina in STZ-Induced diabetic rats.

Diabetes mellitus is the most common metabolic disorder characterized by chronic hyperglycemia. There has been a surge of research studies aiming to use natural products in the management of diabetes. The objective of this study was to isolate and characterize the structure and anti-diabetic mechanisms of the main ingredient from Rosa canina. The oligosaccharide was isolated from Rosa canina fruits and characterized by a combination of FTIR, NMR and Mass spectrometry. Wistar rats were divided into negative control, diabetic (type 2), isolated oligosaccharide (IO)-treated diabetic and positive diabetic controls. Oral glucose tolerance, gluconeogenesis and α-glucosidase inhibitory tests as well as immunohistochemistry and quantitative real time-PCR were performed to elucidate the molecular anti-diabetic mechanisms of IO. Structural analyses confirmed the oligosaccharide structure of isolated fraction. Gluconeogenesis and α-glucosidase activity were inhibited by IO in diabetic rats. The oral glucose tolerance test was improved significantly in the group treated with the IO (P < 0.05). Pancreatic ß-cells and tissue pathological examination showed a significant improvement after the treatment period. In addition, the expression of Ngn3, Nkx6.1 and insulin increased in oligosaccharide-treated compared to untreated diabetic rats. Owing to the verified anti-diabetic effects and regenerative potential, isolated oligosaccharide could be considered as the promising drug in the management of diabetes.

Estimation of gestational diabetes mellitus and dose-response association of BMI with the occurrence of diabetes mellitus in pregnant women of the west of Iran.

The authors aim to investigate the GDM and the dose-response association of BMI with it in pregnant women in Kermanshah, Iran. During the 2015-2016 year, the 1010 pregnant women were studied. The restricted cubic spline method was used to evaluate the relationship between BMI and GDM. The risk of GDM was 10.1%. The incidence rate ratio for GDM indicates a non-significant protective effect and, then a significant risk for GDM occurrence along with BMI. BMI can be used as a predictive factor. A healthy diet and recommended levels of physical activity are suggested to prevent overweight and obesity and subsequent GDM.

Genetic Study of Hepatocyte Nuclear Factor 1 Alpha Variants in Development of Early-Onset Diabetes Type 2 and Maturity-Onset Diabetes of the Young 3 in Iran.

BACKGROUND: Maturity-onset diabetes of the young (MODY) is a clinically and genetically heterogeneous group of diabetes characterized by noninsulin-dependent, autosomal-dominant disorder with strong familial history, early age of onset, and pancreatic beta-cell dysfunction. Mutations in at least 14 different genes are responsible for various MODY subtypes. Heterozygous mutations in the hepatocyte nuclear factor 1 alpha (HNF1A) gene are responsible for the MODY3 subtype, which is a common subtype of MODY in different studied populations. To date, more than 450 different variants of this gene have been reported as disease causing for MODY3. This study was carried out to evaluate HNF1A mutations in Iranian diabetic families fulfilling MODY criteria. MATERIALS AND METHODS: Polymerase chain reaction and Sanger sequencing were performed. All the ten exons of the HNF1A gene were sequenced in ten families, followed by cosegregation analysis and in silico evaluation. Computational protein modeling was accomplished for the identified mutation. RESULTS: MODY3 was confirmed in two large families by detecting a mutation (p.G253E) in coding regions of HNF1A. Compound heterozygous state for two common variants in HNF1A (p.I27 L and p.S487N) was detected in affected members of 5 families, and in one family, a rare benign variant in the coding sequence for Kozak sequence was detected. Two new nonpathogenic variants were found in noncoding regions of HNF1A. CONCLUSION: It seems that HNF1A mutations are a common cause of MODY in Iranian diabetic patients. Identified common variants in heterozygous state can cause diabetes Type II in earlier ages. The role of rare variant rs3455720 is unknown, and more investigation is needed to uncover the function of this variant.

The effect of self-management education through weblogs on the quality of life of diabetic patients.

BACKGROUND: Self-management education of diabetes which is one of the most important noncommunicable diseases worldwide involves facilitating knowledge, skills, and ability required for self-care in these patients. Concerning the progressive growth of use of Internet for educating patients and absence of different studies about education through use of weblogs in patients with diabetes in Iran, the present study was conducted with the aim of determining the effect of self-management education through weblogs on the quality of life of affect the patients. METHODS: This study was performed as intervention on patients referring to diabetes clinic of Talghani hospital in Kermanshah in winter 2018 and spring 2019. The samples consisted of 98 patients with diabetes chosen through available sampling and randomly assigned into study and control groups. For data collection, diabetes quality of life (DQOL) short form clinical questionnaire, Persian version, was used. The intervention involved training self-management conducted through 60 sessions via a designed weblog. The obtained information was introduced into SPSS 21, and analyzed through Mann-Whitney, t-test, and paired t-test. RESULTS: According to the results of this study, the mean age of the examined patients was 32.1 ± 4.9 years, where the major participants were male (n = 52 in the test group, 52.5%). The results showed that after the intervention, the test and control groups were different in terms of anthropometric variables and metabolic indicators; the mean waist circumference in the test and control groups was 98.6 ± 9.8 and 101.5 ± 7.8, respectively; the mean FBS following the intervention in the test and control groups was 131.08 ± 16.04 and 238.2 ± 40, respectively; and the mean BMI postintervention in the test and control groups was obtained as 27.3 ± 3.4 and 30.1 ± 3.8 respectively, where these differences were significant according to independent t-test (p < 0.05). The mean score of quality of life postintervention in the test and control groups was obtained as 56.1 and 49.9 respectively; according to Mann-Whitney test, the difference between the two groups was significant (p < 0.05). CONCLUSION: The results of the present study revealed the positive effect of weblog based self-management on the quality of life of patients with diabetes following the intervention. Further, reduced levels of FBS, BMI, as well as systolic and diastolic blood pressure were also observed, which could be due to increased awareness of patients about their abilities, its risks, as well as the ways to control and treat it.

Self-care Education Needs in Gestational Diabetes Tailored to the Iranian Culture: A Qualitative Content Analysis.

BACKGROUND: Gestational diabetes is one of the most common health problems in pregnancy that requires participation through self-care to reduce the maternal and neonatal complications. The present study aimed to determine the needs of women as an essential first step to formulate a self-care guide fitting the Iranian culture. MATERIALS AND METHODS: The present qualitative study was conducted through interviews with 13 diabetic pregnant women and 10 care providers using semi-structured questionnaires in several cities of Iran in 2016. Further, the data analysis was performed using conventional content analysis. In addition, purposive sampling was performed at the diabetes clinic of Kermanshah University of Medical Sciences, Imam Reza Hospital, and health centers across Kermanshah, Shahroud, and Tehran. RESULTS: In the present qualitative content analysis study, four themes were identified: awareness and ability (knowing diabetes, mothers training and empowerment, continuity and quality, information resources), lifestyle (healthy diet, physical activity), mental health (counseling, interaction, spirituality, and religion), and supportive family (the husband's unique role, the psychological atmosphere at home). CONCLUSIONS: The present study highlighted main aspects of self-care educational/supportive needs, specifically in the domains of lifestyle, awareness and capability, mental health, and family. The results of our analysis highlighted the needs that can be useful for developing comprehensive self-care educational programs, with a higher focus on physical activity, mental health, the role of the family, and the use of religious interests.

The effect of selenium supplementation on acute phase reactants and thyroid function tests in hemodialysis patients.

BACKGROUND: Selenium deficiency is a common problem in patients with chronic kidney disease (CKD). This micronutrient has anti-inflammatory and anti-oxidant effects. Selenium is also found in high concentrations in the thyroid gland. OBJECTIVES: To determine the effect of selenium supplementation on thyroid function tests and acute phase reactants in hemodialysis patients. PATIENTS AND METHODS: In this double-blinded randomized clinical in 3 months, 64 hemodialysis patients with selenium deficiency were divided into experimental (received selenium supplementation; 32 cases) or control group (received placebo; 32 cases). Erythrocyte sedimentation rate (ESR), ferritin, quantitative C-reactive protein (CRP) and thyroid function tests (TFTs) including thyroid stimulating hormone (TSH), T3 resin uptake (T3RU), and free T4 were measured before and after the intervention and compared between experimental and control groups. RESULTS: At baseline, no significant difference was found between experimental and control groups regarding CRP, ESR and ferritin serum levels. Likewise, after intervention, no significant difference was found between experimental and control groups for CRP (14.77 ± 17.93 vs. 18.29 ± 21.56 mg/L), ESR (32.90 ± 32.62 vs. 33.91 ± 31.15 mm/h) and ferritin (528.6 ± 423.07 vs. 519.52 ± 345.59 ng/mL). At baseline, no significant difference was found between experimental and control groups regarding TFTs. Likewise, after intervention, no significant difference was found between experimental and control groups for TSH (3.7 ± 2.22 vs. 2.84 ± 1.88 µU/mL), free T4 (7.19 ± 1.98 vs. 7.02 ± 1.87 µg/dL) and T3RU (30.04 ± 2.28% vs. 29.2 ± 1.98%). CONCLUSIONS: Oral selenium supplementation for three months did not have any significant effect on thyroid function tests or acute phase reactants.

To differentiate benign from malignant thyroid nodule comparison of sonography with FNAC findings.

OBJECTIVES: To evaluate the diagnostic accuracy of sonography and Fine Needle Aspiration Cytology (FNAC). METHODOLOGY: This follow-up study was approved by review board and conducted at Endocrine Clinic and Radiology Department of Imam Reza, Kermanshah. The patients were diagnosed to have thyroid nodule examined by FNA and Sonography suspicious malignant cases underwent surgery. RESULTS were entered in SPSS 11.5 chi-Square and Fisher exact test applied to compare malignant and benign nodule characters. RESULTS: In this study 144 patients were examined and 14 cases (9.7%) had malignant nodule. Most of malignant nodules were single (p=0.001), solid (p < 0.001), hypo-echo (p=0.001), with irregular margins (p < 0.001) and with calcification (p=0.041). There was no significant relationship between malignancy and nodule size of larger than 15 mm (p=0.395). Compared with surgery, FNA sensitivity and specificity were calculated as 92.8% and 100% respectively. CONCLUSION: Based on the result of this study, thyroid nodule size must not be considered as a criterion for malignancy and thyroid nodules of any size must be suspected as malignant. Important criteria for malignancy include irregular edges, being solid, hypoechogenicity and being a single nodule respectively. Compared with Surgery, FNA Sensitivity and specificity were calculated as 92.8% and 100% respectively.

Effect of selenium on immune response against hepatitis B vaccine with accelerated method in insulin-dependent diabetes mellitus patients.

BACKGROUND: Poor response to various vaccines especially hepatitis B is common. The purpose of this study was to evaluate the effect of selenium on immune response against hepatitis B vaccine with accelerated method in insulin-dependent diabetes mellitus patients. METHODS: In this randomized clinical trial study, 62 insulin dependent diabetic patients were divided into case and control groups (each of 31 cases). In the control group, hepatitis B vaccine 20 µg was done by intra-deltoid injection on a 0, 10, 21 day schedule with placebo, and in case group, 200 µg of selenium as a supplement was added once daily to same vaccine schedule from the first day to the 30(th) day of the month. After one month, serum sample was obtained and evaluated for anti-HBs using ELISA method. Data were collected and analyzed. RESULTS: In the case group, 23 cases (74.2%) and in control group, 15 cases (48.4%) achieved protective level of anti-HBs irrespective to sex and age (p=0.037). The mean antibody levels were 233.75±163.45U/L and 144±69.29U/L in selenium and control groups, respectively. CONCLUSION: Our study showed that selenium could help to increase protective rate and level of anti-HBs by accelerated vaccination method. Adding selenium by routine HBV vaccination in diabetic patients is recommended for increasing the rate and level of anti-HBs in such group.

Treatment of depression in type 2 diabetes with Fluoxetine or Citalopram?

OBJECTIVE: Comparing the antidepressant effects of Citalopram with Fluoxetine and their effect on glycemic control in diabetic patients. METHODS: Forty patients attending the Diabetes Research Center in Kermanshah University of Medical Sciences, Kermanshah, Iran from September 2006 to October 2007 with type II diabetes and suffering from major depression were randomly assigned to 2 groups (n=20 per group) in a randomized controlled trial method. They received up to 40 mg/d of Fluoxetine or Citalopram. Twelve weeks after treatment, patients were reassessed in terms of severity of depression and diabetic status. The Beck Depression Inventory (BDI) and psychiatric interview were used to measure the severity of depression and follow up the patients. Glycosylated hemoglobin (HbA1c) levels and fasting blood sugar (FBS) was obtained to monitor glycemic control. RESULTS: After the 12-week treatment, both groups showed significant improvement in severity of depression, FBS, and HbA1c. There were no significant differences between the 2 groups in terms of improvement in depression and diabetic status. CONCLUSION: Fluoxetine and Citalopram can effectively reduce the severity of depression in diabetic patients without an adverse effect on glycemic control.

The frequency of factor V Leiden mutation, ACE gene polymorphism, serum ACE activity and response to ACE inhibitor and angiotensin II receptor antagonist drugs in Iranians type II diabetic patients with microalbuminuria.

The aim of present study was to determine if factor V Leiden (FVL) mutation and angiotensin converting enzyme insertion/deletion (ACE I/D) polymorphism are associated with diabetic nephropathy (DN) among Kurdish population from Western Iran. This case-control study comprised 144 unrelated adult type 2 diabetic mellitus patients (T2DM) including 72 patients with microalbuminuria and 72 age and sex matched patients without nephropathy. The ACE I/D polymorphism and FVL mutation were detected by polymerase chain reaction (PCR) and PCR-RFLP, respectively. The frequency of FVL G1691A and ACE D allele in T2DM patients with microalbuminuria were 1.6 and 57%, respectively and in normoalbuminuric T2DM patients were 4.9 and 58.3%, respectively (P > 0.05). ACE genotypes affected on serum ACE activity and a better response to ACE inhibitor therapy (captopril) compared to angiotensin II receptor antagonist (losartan) was obtained with significant reduction of ACE activity in diabetic patients without nephropathy carrying DD genotype. However, the beneficial effect of losartan therapy was observed in microalbuminuric patients with II genotype compared to ID and DD genotypes.

Post partum depression and thyroid function.

OBJECTIVE: Risk of depression is particularly high for women during the prenatal period. Various investigators have attempted to establish a link between thyroid function and post partum depression. This study aimed to investigate whether thyroid function differs in women with postpartum depression compared to a control group. METHODS: In this case-control study, subjects were selected from Obstetrics & Gynecology and Psychiatric clinics of Kermanshah University of Medical Sciences. Forty eight patients suffering from postpartum depression according to Diagnostic and Statistical Manual of Mental Disorders, fourth edition totally revised (DSM-IV-TR), and 65 normal controls underwent diagnostic evaluation by one trained psychiatrist using Structured Clinical Interview for DSM-IV-TR. Then, the demographic questionnaire and the Persian version of Edinburgh Postnatal Depression Scale (EPDS) were completed by the participants. Finally, their thyroid functions were assessed. Data analyses were done using the SPSS program 13. RESULTS: No statistically significant differences were observed between thyroid function tests and postpartum depression. According to multiple regression analysis with stepwise method, subjects with lower serum TSH, T3RU, T3 levels, younger age and longer period after delivery tended to have higher EPDS scores (P-value=0.008). CONCLUSION: The present study reports that those women with postpartum depression had a no greater prevalence of thyroid dysfunction than the control subjects. It seems that thyroid dysfunction should be considered in women with postpartum depression individually, but the role of thyroid as an important cause of this condition is not yet established. This suggests that future studies should concentrate on this concept in postpartum depression.

Synergistic effects of the MTHFR C677T and A1298C polymorphisms on the increased risk of micro- and macro-albuminuria and progression of diabetic nephropathy among Iranians with type 2 diabetes mellitus.

OBJECTIVES: To find whether polymorphisms of methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C are risk factors for diabetic nephropathy (DN) among type 2 diabetes mellitus (T2DM) patients from Western Iran. DESIGN AND METHODS: The MTHFR polymorphisms were detected in 72 microalbuminuric, 68 macroalbuminuric and 72 normoalbuinuric T2DM patients by PCR-RFLP. RESULTS: The possession of both MTHFR 677T and 1298C alleles increase the risk of microalbuminuria to 4.3-fold (p=0.007) in T2DM patients. The presence of either MTHFR 677T, 1298C allele is sufficient to increase the risk of macroalbuminuria in T2DM patients by 4.1 and 5.5 times (p=0.027, and p=0.006, respectively). The concomitant presence of both 677T and 1298C alleles act in synergy to increase the risk of macroalbuminuria by 20.4-fold (p<0.001) and progression of DN from microalbuminuria to macroalbuminuria (OR=4.73, p=0.01). CONCLUSION: Both MTHFR 677T and 1298C alleles increased the susceptibility to the onset and progression of DN in Iranians with T2DM.

Coblation assisted excision of lingual thyroid.

Lingual thyroid (LT) tissue is the most frequent ectopic location of the thyroid gland. We report 5 cases of symptomatic LT and discuss the new surgical approach. Transoral approach and coblation assisted excision of LT was performed. Postoperative follow-up for all patients was like as tonsillectomy management without tracheotomy. It's seem that this approach is much better than other such as tongue-splitting, transcervical transhyoid, pharyngotomy, with an infrahyoid approach, combined cervical and intraoral approach, Mandibular midline osteotomy.