The effect of curcumin and high-content eicosapentaenoic acid supplementations in type 2 diabetes mellitus patients: a double-blinded randomized clinical trial.

BACKGROUND/OBJECTIVES: The present study investigated the effect of curcumin and eicosapentaenoic acid, as one the main components of omega-3 polyunsaturated fatty acids, on anthropometric, glucose homeostasis, and gene expression markers of cardio-metabolic risk in patients with type 2 diabetes mellitus. SUBJECTS/METHODS: This clinical trial was conducted at the Endocrinology Clinic of Imam Reza Hospital in Tabriz. It aimed to determine the impact of Eicosapentaenoic Acid (EPA), Docosahexaenoic Acid (DHA), and curcumin supplements on various health indicators in patients with Type 2 Diabetes Mellitus (DM2) from 2021.02.01 to 2022.02.01. The study was a randomized double-blinded clinical trial and conducted over 12 weeks with 100 participants randomly divided into four groups. Stratified randomization was used to assign participants to two months of supplementation based on sex and Body Mass Index (BMI). The study comprised four groups: Group 1 received 2 capsules of 500 mg EPA and 200 mg DHA, along with 1 nano-curcumin placebo; Group 2 received 1 capsule of 80 mg nano-curcumin and 2 omega 3 Fatty Acids placebos; Group 3 received 2 capsules of 500 mg EPA and 200 mg DHA, and 1 capsule of 80 mg nano-curcumin; Group 4, the control, received 2 omega 3 Fatty Acids placebos and 1 nano-curcumin placebo. RESULTS: After twelve weeks of taking EPA + Nano-curcumin supplements, the patients experienced a statistically significant reduction in insulin levels in their blood [MD: -1.44 (-2.70, -0.17)]. This decrease was significantly greater than the changes observed in the placebo group [MD: -0.63 (-1.97, 0.69)]. The EPA + Nano-curcumin group also showed a significant decrease in High-Sensitivity C-Reactive Protein (hs-CRP) levels compared to the placebo group (p < 0.05). Additionally, the EPA + Nano-curcumin group had a significant increase in Total Antioxidant Capacity (TAC) levels compared to the placebo group (p < 0.01). However, there were no significant differences in Fasting Blood Sugar (FBS), Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) index, Quantitative Insulin Sensitivity Check Index (QUICKI), or Hemoglobin A1c (HbA1C) levels between the four groups (all p > 0.05). There were significant differences between the Nano-curcumin and EPA groups [MD: -17.02 (-32.99, -1.05)], and between the Nano-curcumin and control groups [MD: -20.76 (-36.73, -4.79)] in terms of lowering the serum cholesterol level. The difference in Triglycerides (TG) serum levels between the EPA + Nano-curcumin and placebo groups were not statistically significant (p = 0.093). The Nano-curcumin group showed significant decreases in Low-Density Lipoprotein (LDL) levels compared to the EPA group [MD: -20.12 (-36.90, -3.34)] and the control group [MD: -20.79 (-37.57, -4.01)]. There was a near-to-significant difference in High-Density Lipoprotein (HDL) serum levels between the EPA + Nano-curcumin and EPA groups (p = 0.056). Finally, there were significant differences in the decrease of serum Vascular Endothelial Growth Factor (VEGF) levels between the EPA and Nano-curcumin groups [MD: -127.50 (-247.91, -7.09)], the EPA and placebo groups [MD: 126.25 (5.83, 246.66)], the EPA + Nano-curcumin and Nano-curcumin groups [MD: -122.76 (-243.17, -2.35)], and the EPA + Nano- curcumin and placebo groups [MD: 121.50 (1.09, 241.92)]. CONCLUSIONS: The findings of the present study suggest that 12-week supplementation with EPA and Nano-curcumin may positively impact inflammation, oxidative stress, and metabolic parameters in patients with diabetes. The supplementation of EPA and Nano-curcumin may be a potential intervention to manage diabetes and reduce the risk of complications associated with diabetes. However, further research is needed to validate the study's findings and establish the long-term effects of EPA and Nano-curcumin supplementation in patients with diabetes.

Serum neuregulin 4 (NRG-4) level and non-alcoholic fatty liver disease (NAFLD): A case-control study.

OBJECTIVE: The current case-control study aimed to examine the association of circulating neuregulin 4 (NRG-4), a brown fat-enriched endocrine factor, with non-alcoholic fatty liver disease (NAFLD). METHODS: A total of 50 patients newly diagnosed with NAFLD with 50 age-matched and sex-matched subjects without NAFLD were recruited in the present study. Circulating NRG-4 levels were assessed with an enzyme-linked immunosorbent assay (ELISA) kit. SPSS version 23 was used for statistical analysis. RESULTS: Patients with NAFLD had lower levels of circulating NRG-4 than the control group (P < .001). Participants in the highest quartile of circulating NRG-4 had significantly lower body mass index (BMI), waist circumference (WC), triglyceride (TG) and homeostatic model assessment for insulin resistance (HOMA-IR) compared with those in the lowest quartile (all P < .01). The prevalence of NAFLD in the quartile 4 of the serum NRG-4 level was 38.46%, lower than the quartile 1 (62.50%, P = .006), quartile 2 (52.00%, P = .017) and quartile 3 (48.00%, P = .032). In multiple stepwise regression analysis, BMI (ß = -0.712, P = .016), WC (ß = -0.577, P = .023), TG (ß = -0.509, P = .001), high-density lipoprotein cholesterol (HDL-C) (ß = 0.489, P = .001) and HOMA-IR (ß = -0.609, P = .003) were independently related to serum NRG-4 level. The odds of NAFLD decreased by 41% per 1 SD increase in serum NRG-4 level (OR, 0.59; 95% CI, 0.35-0.78; P = .021), after adjustment for all potential confounders. CONCLUSION: The results of the present study demonstrate that circulating NRG-4 levels may play a protective role in NAFLD.

The relationship between serum 25-hydroxy vitamin D and blood pressure and quality of life in overweight and obese patients with type 2 diabetes mellitus compared with healthy subjects.

BACKGROUND: Vitamin D is one of the known lipoprotein hormones with metabolic properties. We aimed to determine the serum 25-hydroxy vitamin D concentration in overweight/obese subjects with diabetes mellitus type Ⅱ (DM Ⅱ) in association with systolic and diastolic blood pressure and quality of life compared with healthy participants. METHODS: The current case-control study was carried out among 80 overweight/obese subjects with DM Ⅱ, and 77 healthy subjects matched by sex, age and body mass index (BMI). Serum 25-hydroxyvitamin D concentration was measured by ELISA method. In order to examine the quality of life, the Persian version of SF36 questionnaire was used. RESULTS: There was significant difference between diabetic and healthy subjects considering serum 25-hydroxyvitamin D concentration (p=0.012). Serum 25-hydroxyvitamin D concentration was inversely correlated with diastolic blood pressure (p=0.02) and positively associated with physical function (p<0.001), social function (p<0.001) and general health (p<0.001) components of quality of life in diabetic subjects and physical health sub-scale (p=0.004) in all participants. CONCLUSION: Serum 25-hydroxyvitamin D concentration was significantly lower in diabetic subjects in comparison with healthy controls. There was a significant reverse relationship between serum concentrations of 25-hydroxyvitamin D with diastolic blood pressure and on the other hand, a significant positive relationship with physical function, social function and general health components and physical health subscale of quality of life in participants with DM Ⅱ.

A pilot trial of metformin for insulin resistance and mood disturbances in adolescent and adult women with polycystic ovary syndrome.

We examine the effects of metformin on insulin resistance (IR) and mood including in adolescent and adult women with polycystic ovary syndrome (PCOS). This trial was conducted in 19 adolescents (age ≤18 years) and 25 adult (age >18 years) women with PCOS. Anthropometric and measurements including, serum glucose, endocrine panel, and lipid profile were performed at baseline. IR was measured by Homeostasis Model Assessment IR (HOMA-IR). Anxiety and depression were measured by Beck's Anxiety (BAI) and Depression Inventories (BDI-II). All tests were repeated after a 90-day treatment with metformin (1,500 mg/day). The severity of depression and anxiety decreased after 90-day treatment with metformin in women diagnosed with PCOS. The BAI scores were higher in adolescent group while BDI-II scores were higher in the adult group (p = .016). After 90-day metformin treatment, both BDI-II and BAI scores were decreased by 3.3 and 3.4, respectively (p < .001). Indicators of IR and obesity were improved with this therapy. Although the adolescents weighed lower than the adults, baseline HOMA-IR 5.5 ± 1.7 was higher in this group than 4.4 ± 1.2 in the adult women (p =.022). The findings suggest that metformin decrease IR and improve mood both in adolescent and adult women with PCOS.

Association between FTO gene polymorphisms and type 2 diabetes mellitus, serum levels of apelin and androgen hormones among Iranian obese women.

BACKGROUND AND AIMS: Recent studies show that FTO single nucleotide polymorphisms (SNPs) are associated with obesity and type 2 diabetes mellitus (T2DM). On the other hand, many animal models and clinical studies have demonstrated that apelin, an adipocytokine, is related to the obesity and T2DM. Additionally, obese women are at risk of Hyperandrogenemia. So, the aim of this study was to investigate the relationship between FTO variants (rs763967273, rs759031579, rs141115189, rs9926289, rs76804286 and rs9939609) with T2DM, serum apelin and androgenic hormones in Iranian obese women. SUBJECTS AND METHODS: 197 obese women (123 women with T2DM and 74 women as healthy control) were participated in this study. Anthropometrical and biochemical characteristics were measured. Serum apelin and androgen hormones levels were determined in 66 subjects consisting of 33 cases and 33 controls. PCR were carried out and subsequently, the PCR production was genotyped by Sanger sequencing assay. RESULTS: Our observations showed that all SNPs are related to T2DM. The rs9926289 FTO variant had a strong association with serum apelin and dehydroepiandrosterone-sulfate levels (P=0.04 and P=0.03, respectively) among SNPs. In addition, apelin and androgenic hormones were correlated with T2DM. Two polymorphisms including rs9939609 and rs9926289 had a strong Linkage disequilibrium (r2=1). CONCLUSION: FTO variants not only were associated with T2DM, but also some variants had a strong association with apelin and androgenic hormones profile.

Effective Phages as Green Antimicrobial Agents Against Antibiotic-Resistant Hospital Escherichia coli.

BACKGROUND: Bacteriophages are viruses that attack bacteria and lead to their lysis in an efficient and highly specific manner. These natural enemies of bacteria were used as therapeutic agents before the advent of antibiotics. Currently, with the rapid spread of multi-drug resistant bacteria, phage therapy can be an effective alternative treatment for antibiotic resistant bacteria. OBJECTIVES: This study evaluated the effectiveness of bacteriophages in removing antibiotic-resistant clinical Escherichia coli strains in vitro and in vivo. PATIENTS AND METHODS: Different samples were taken from bed sore and foot ulcers of patients with diabetes. E. coli strains were isolated and identified by standard methods. The antibiogram was ascertained using the Kirby Bauer disc diffusion method for ten antibiotics. The bacteriophages were isolated from environmental water samples. They were exposed to the host bacteria by the double-layer agar technique (DLA) to observe plaques. Cross reaction of the phages on test E. coli strains was performed to determine broader-spectrum phages. Phage TPR7 was selected for animal trials. Five groups of mice including a control group, bacterial group, phage group, antibiotic therapy group and phage therapy group, were examined. RESULTS: Ten E. coli strains were isolated from hospital samples. They showed high resistance to the used antibiotics. An effective bacteriophage was isolated for each strain. The cross-reaction showed phages which affect more than six E. coli strains. They can be a good choice for clinical therapeutic use. In animal trials the group challenged with phages after being infected showed similar results as the group treated with gentamicin after being infected. In both groups infection was removed after 48 hours. CONCLUSIONS: According to the results, six strains were resistant to six or seven antibiotics and all strains were at least resistant to two antibiotics. However, for each of these resistant bacteria one bacteriophage was isolated from environmental samples, which showed the effectiveness of bacteriophages to remove clinically resistant E. coli strains. Effective phages in vitro showed effective results in vivo as well.

Is there a value for probiotic supplements in gestational diabetes mellitus? A randomized clinical trial.

BACKGROUND: Although several studies have found probiotics encouraging in prevention of gestational diabetes mellitus (GDM), the evidence for the use of probiotics in diagnosed GDM is largely limited. The aim of this study was to assess the effect of a probiotic supplement capsule containing four bacterial strains on glucose metabolism indices and weight changes in women with newly diagnosed GDM. METHODS: Sixty-four pregnant women with GDM were enrolled into a double-blind placebo-controlled randomized clinical trial. They were randomly assigned to receive either a probiotic or placebo capsule along with dietary advice for eight consecutive weeks. The trend of weight gain along with glucose metabolism indices was assayed. RESULTS: During the first 6 weeks of the study, the weight gain trend was similar between the groups. However, in the last 2 weeks of the study, the weight gain in the probiotic group was significantly lower than in the placebo group (p < 0.05). Fasting blood sugar (FBS) decreased in both intervention (from 103.7 to 88.4 mg/dl) and control (from 100.9 to 93.6 mg/dl) groups significantly, and the decrease in the probiotic group was significantly higher than in the placebo group (p < 0.05). Insulin resistance index in the probiotic group had 6.74% reduction over the study period (p < 0.05). In the placebo group, however, there was an increase in insulin resistance index (6.45%), but the observed change in insulin resistance was not statistically significant. Insulin sensitivity index was increased in both groups. The post-intervention insulin sensitivity index in the probiotic group was not significantly different from placebo when adjusted for the baseline levels. CONCLUSIONS: The probiotic supplement appeared to affect glucose metabolism and weight gain among pregnant women with GDM. This needs to be confirmed in other settings before a therapeutic value could be approved.

Primary hyperaldostronisim as initial presentation of adrenal cortical carcinoma with liver metastasis: a case report.

Adrenocortical carcinoma (ACC) is a rare tumor and usually a fatal disease which can develop at any age in either sex. Differential diagnosis between malignant and benign adrenal mass is not easy which leads to significant clinical challenge for optimal treatment. Here we report a 22-year-old woman diagnosed with primary hyper aldostronism initially but disease relapsed during six months and magnetic resonance imaging revealed tumor with metastasis to the liver.

Angiotensin receptor blocker and N-acetyl cysteine for reduction of proteinuria in patients with type 2 diabetes mellitus.

INTRODUCTION: Proteinuria and albuminuria are established risk factors for progressive renal damage. Albuminuria can be effectively controlled by antihypertensive drugs that interrupt the renin-angiotensin-aldosterone system. However, the efficiency of N-acetyl cysteine (NAC) in preventing diabetic nephropathy is uncertain. Renoprotective effects of angiotensin receptor blockers and NAC in preventing or reducing of proteinuria in patients with diabetic nephropathy was studied. MATERIALS AND METHODS: In a randomized controlled trial, 70 patients with type 2 diabetic nephropathy (proteinuria and renal insufficiency) were studied. The patients were randomly divided into two groups and were treated with losartan, 25 mg, twice per day, with and without NAC, 600 mg twice daily (study and control groups, respectively; 35 patients in each group). Urine protein was checked before treatment and after 2 months of treatment. RESULTS: The two groups were comparable regarding gender, age, serum creatinine, and urine protein excretion levels. Proteinuria improved in both groups. The mean proteinuria level decreased more in patients with losartan and NAC; however, comparison of proteinuria between the two groups showed no significant difference after 2 months. CONCLUSIONS: Angiotensin receptor blockers reduced proteinuria due to diabetic nephropathy, and this study failed to detect additional effect when NAC was combined with these medications.

Electrophysiologic changes in patients with untreated primary hypothyroidism.

Thyroid diseases may cause signs and symptoms of neuromuscular dysfunction. Hypothyroidism has been associated with the clinical features of proximal muscle weakness, mononeuropathy, and sensorimotor polyneuropathy. This study aimed at evaluating the electrophysiologic findings in patients with untreated spontaneous hypothyroidism and comparing them with a healthy control group. In a case-control cross-sectional study, 40 patients with definite diagnosis of clinical hypothyroidism and 40 healthy control subjects were evaluated by electromyography and nerve conduction studies in the specialized clinic of the Tabriz University of Medical Sciences during an 18-month period. Seven male and 33 female patients with a mean age of 39.5 ± 11.8 years were enrolled. In this group, there were 12 cases (30%) with clinical muscle weakness, with severity of approximately 4/5, 18 cases (45%) with decreased or absent deep tendon reflexes, 6 cases (15%) with neuropathy, including 4 sensory and 2 sensorimotor, of which 5 cases were mild and 1 case was moderate, 3 cases (7.5%) with myopathy, and 13 cases (32.5%) with carpal tunnel syndrome, which was mild in 7, moderate in 10, and severe in 2 hands. Patients with neuropathy were significantly older than those without neuropathy (P = 0.001). There was no significant relation between gender, duration of the disease, serum TSH level, and the presence of clinical muscle weakness with the occurrence of neuropathy or myopathy. Female gender, increasing age, duration of the disease, and the frequency of clinical weakness were, however, significantly related to the presence of carpal tunnel syndrome (P < 0.05). In conclusion, in patients with untreated primary hypothyroidism, majority had the carpal tunnel syndrome. Mild neuropathy mainly of sensory type and myopathy were uncommon and rare findings, respectively. Early treatment would hinder the progression of mentioned abnormalities and minimize their occurrence.

End-tidal CO(2) levels lower in subclinical and overt hypothyroidism than healthy controls; no relationship to thyroid function tests.

BACKGROUND: Hypoventilation is a frequently suspected complication of hypothyroidism. OBJECTIVE: In this study we examined the hypothesis that changes in alveolar ventilation, as measured by end-tidal carbon dioxide (Et-CO(2)), differ between patients with mild (subclinical) and overt (clinical) thyroid hormone deficiency, and both differ from healthy control subjects. METHODS: A total of 95 subjects, including 33 with subclinical hypothyroidism (an elevated thyroid-stimulating hormone (TSH) level and a normal thyroxin (fT(4)) level), 31 with overt hypothyroidism (elevated TSH and decreased fT(4)), and 31 healthy controls. All subjects were female and were evaluated clinically by an endocrinologist for evidence of thyroid disease and categorized on the basis of thyroid hormone levels. Et-CO(2) was measured using a capnograph. Et-CO(2) levels were measured three times and the mean value was considered as the mean level for the individual. RESULTS: Mean Et-CO(2) values of the subclinical hypothyroidism group were significantly lower than those of the healthy controls (31.79 ± 2.75 vs 33.81 ± 2.38; P = 0.01). Moreover, mean Et-CO(2) values for the overt hypothyroidism group were significantly lower than those for healthy controls (32.13 ± 3.07 vs 33.81 ± 2.38; P = 0.04). There was a significant correlation between Et-CO(2) values and TSH levels (r = -0.24; P = 0.01). However, Et-CO(2) values were not correlated with fT(4) levels (r = 0.13; P = 0.20). CONCLUSIONS: Alveolar ventilation, as inferred from lower Et-CO(2) levels, is higher in subjects with subclinical hypothyroidism and overt hypothyroidism (lower Et-CO(2)) than in healthy controls. Furthermore, Et-CO(2) levels have no relationship to the levels of TSH or fT(4). The lower Et-CO(2) in these patients with hypothyroidism, particularly at the subclinical stage, suggests presence of hyperventilation, which may be related to direct effect of TRH on respiratory center or to local changes within the lung.

Vitamin D status in healthy postmenopausal Iranian women.

BACKGROUND: There are few epidemiologic studies on vitamin D status of postmenopausal women in the Middle East countries. This study aimed to investigate the 25-hydroxyvitamin D levels in postmenopausal women living in the north-west of Iran. METHODS: Using the records of the local household registry, 300 cases were enrolled by simple random sampling. Serum 25-hydroxyvitamin D levels were determined by fully automated chemiluminescent immunoassay. In addition, the study included survey questions regarding age, body weight and height, use of supplements and skin protection agents and clinical and reproductive histories. RESULTS: Our cases had the mean age of 63.41 ± 4.64 years with menopause duration of 16.79 ± 6.15 years. Median and interquartile 25-75 range of vitamin D were 14.20 ng/ml and 7-37.2 ng/ml respectively. We found hypovitaminosis D [25(OH) D < 10 ng/ml] in 38.3% of our cases. Serum 25(OH) D concentrations were not significantly correlated with age or BMI. CONCLUSIONS: These findings indicate that 25(OH) D levels in postmenopausal women of north-west Iran are low. Studies to elucidate and assess the dietary intake of vitamin D in elderly women of this region can be of further benefit.

Albuminuria and its correlates in an Iranian type 2 diabetic population.

OBJECTIVE: To study the prevalence and correlates of increased urinary albumin excretion (UAE) in an Iranian type 2 diabetic population. METHODS: Over a one year period since October 2002, 400 consecutive type 2 diabetic patients referred to an outpatient diabetes clinic, were enrolled in a cross sectional study. Subjects had no history of renal impairment or overt proteinuria. Data concerning demographic characteristics and cardiovascular risk factors were recorded and height, weight and blood pressure were measured. Glucose, cholesterol, HDL-C, LDL-C, triglyceride, apoprotein B, lipoprotein a, creatinine, and HbA1c were measured in fasting blood samples. Overnight twelve-hour UAE were assessed by immunoturbidometry method. Regression analyses were employed to determine the correlates of UAE. RESULTS: Out of 400 patients, 156 (40%) subjects had increased UAE (UAE > or = 30 mg/24 hour). The UAE was higher in males compared to females (145.5 vs. 72.1 mg/day; p < 0.05); however, the age and HDL adjusted UAE levels were not significantly different between men and women (120.1 vs. and 87.9 mg/day; p = 0.37). Increased UAE was correlated with decreasing HDL-C and a longer duration of diabetes independent of other variables; increased UAE was correlated with HbA1c as well. Age, systolic and diastolic blood pressure, total cholesterol, LDL-C, triglyceride, apoprotein B, lipoprotein a, and GFR did not correlate with increased UAE. CONCLUSION: In this study, increased UAE was considerably frequent among type 2 diabetic patients without any significant history of renal dysfunction. Albuminuria was found to be associated with dyslipidemia (low HDL-C), long duration of diabetes, and uncontrolled glycemia revealed by higher HbA1c.

Burns in diabetic patients.

CONTEXT AND AIMS: Diabetic burn patients comprise a significant population in burn centers. The purpose of this study was to determine the demographic characteristics of diabetic burn patients. MATERIALS AND METHODS: Prospective data were collected on 94 diabetic burn patients between March 20, 2000 and March 20, 2006. Of 3062 burns patients, 94 (3.1%) had diabetes; these patients were compared with 2968 nondiabetic patients with burns. Statistical analysis was performed using the statistical analysis software SPSS 10.05. Differences between the two groups were evaluated using Student's t-test and the chi square test. P < 0.05 was considered as significant. RESULTS: The major mechanism of injury for the diabetic patients was scalding and flame burns, as was also the case in the nondiabetic burn patients. The diabetic burn patients were significantly older, with a lower percentage of total burn surface area (TBSA) than the nondiabetic burn population. There was significant difference between the diabetic and nondiabetic patients in terms of frequency of infection. No difference in mortality rate between diabetic and nondiabetic burn patients was observed. The most common organism in diabetic and nondiabetic burn patients was methicillin-resistant staphylococcus. Increasing %TBSA burn and the presence of inhalation injury are significantly associated with increased mortality following burn injury. CONCLUSIONS: Diabetics have a higher propensity for infection. Education for diabetic patients must include caution about potential burn mishaps and the complications that may ensue from burns.