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Daily coffee consumption is inversely associated with risk of type-2 diabetes (T2D). Cafestol, a bioactive substance in coffee, increases glucose-stimulated insulin secretion in vitro and increases glucose uptake in human skeletal muscle cells. We hypothesized that cafestol can postpone development of T2D in KKAy mice. Forty-seven male KKAy mice were randomized to consume chow supplemented daily with either 1.1 (high), 0.4 (low), or 0 (control) mg of cafestol for 10 weeks. We collected blood samples for fasting glucose, glucagon, and insulin as well as liver, muscle, and fat tissues for gene expression analysis. We isolated islets of Langerhans and measured insulin secretory capacity. After 10 weeks of intervention, fasting plasma glucose was 28−30% lower in cafestol groups compared with the control group (p < 0.01). Fasting glucagon was 20% lower and insulin sensitivity improved by 42% in the high-cafestol group (p < 0.05). Cafestol increased insulin secretion from isolated islets by 75−87% compared to the control group (p < 0.001). Our results show that cafestol possesses antidiabetic properties in KKAy mice. Consequently, cafestol may contribute to the reduced risk of developing T2D in coffee consumers and has a potential role as an antidiabetic drug.

The effects of chronic coffee exposure in models of type 2 diabetes mellitus (T2D) models is scarcely studied, and the efficacy of the main coffee species has never been compared. We tested the hypothesis that long-term consumption of arabica and robusta coffee may differentially delay and affect T2D development in Zucker diabetic fatty rats. Three study groups received either chow mixed with arabica or robusta instant coffee (1.8% w/w) or unsupplemented chow food for 10 weeks. Both coffee species reduced liver triglyceride content and area under the curve of fasting and postprandial insulin. At study end, plasma adiponectin, total cholesterol and high density lipoprotein levels were higher in the robust group compared with both arabica and control groups. The liver gene expression of Glucose-6-phosphatase, catalytic subunit (G6pc) and Mechanistic target of rapamycin (mTOR) in robusta and Cpt1a in both coffee groups was downregulated. In conclusion, long-term consumption of both coffee species reduced weight gain and liver steatosis and improved insulin sensitivity in a rat model of T2D. Robusta coffee was seemingly superior to arabica coffee with respect to effects on lipid profile, adiponectin level and hepatic gene expression.

The literature is inconsistent as to how coffee affects metabolic syndrome (MetS), and which bioactive compounds are responsible for its metabolic effects. This study aimed to evaluate the effects of unfiltered coffee on diet-induced MetS and investigate whether or not phenolic acids and trigonelline are the main bioactive compounds in coffee. Twenty-four male Sprague‒Dawley rats were fed a high-fat (35% W/W) diet plus 20% W/W fructose in drinking water for 14 weeks, and were randomized into three groups: control, coffee, or nutraceuticals (5-O-caffeoylquinic acid, caffeic acid, and trigonelline). Coffee or nutraceuticals were provided in drinking water at a dosage equal to 4 cups/day in a human. Compared to the controls, total food intake (p = 0.023) and mean body weight at endpoint (p = 0.016) and estimated average plasma glucose (p = 0.041) were lower only in the coffee group. Surrogate measures of insulin resistance including the overall fasting insulin (p = 0.010), endpoint HOMA-IR (p = 0.022), and oral glucose tolerance (p = 0.029) were improved in the coffee group. Circulating triglyceride levels were lower (p = 0.010), and histopathological and quantitative (p = 0.010) measurements indicated lower grades of liver steatosis compared to controls after long-term coffee consumption. In conclusion, a combination of phenolic acids and trigonelline was not as effective as coffee per se in improving the components of the MetS. This points to the role of other coffee chemicals and a potential synergism between compounds.

Since coffee may help to prevent the development of metabolic syndrome (MetS), we aimed to evaluate the short- and long-term effects of a coffee-based supplement on different features of diet-induced MetS. In this study, 24 Sprague Dawley rats were divided into control or nutraceuticals groups to receive a high-fat/high-fructose diet with or without a mixture of caffeic acid (30 mg/day), trigonelline (20 mg/day), and cafestol (1 mg/day) for 12 weeks. An additional 11 rats were assigned to an acute crossover study. In the chronic experiment, nutraceuticals did not alter body weight or glycemic control, but improved fed hyperinsulinemia (mean difference = 30.80 mU/L, p = 0.044) and homeostatic model assessment-insulin resistance (HOMA-IR) (mean difference = 15.29, p = 0.033), and plasma adiponectin levels (mean difference = -0.99 µg/mL, p = 0.048). The impact of nutraceuticals on post-prandial glycemia tended to be more pronounced after acute administration than at the end of the chronic study. Circulating (mean difference = 4.75 U/L, p = 0.014) and intrahepatocellular alanine transaminase activity was assessed by hyperpolarized-13C nuclear magnetic resonance NMR spectroscopy and found to be reduced by coffee nutraceuticals at endpoint. There was also a tendency towards lower liver triglyceride content and histological steatosis score in the intervention group. In conclusion, a mixture of coffee nutraceuticals improved insulin sensitivity and exhibited hepatoprotective effects in a rat model of MetS. Higher dosages with or without caffeine deserve to be studied in the future.

The present trial aimed to evaluate the effects of pioglitazone on the mental status of nondiabetic metabolic syndrome patients. From 145 patients screened, 104 eligible volunteers (57% female; age 20–70 years) were enrolled and randomly assigned to receive either pioglitazone (uptitrated to 30 mg/day; P=53) or matching placebo (P=51) for 24 weeks. Depression and anxiety were quantified using the hospital anxiety and depression scale and stress level using the general health questionnaire 12 at baseline, week 12, and endpoint. Homeostasis model assessment was used to estimate insulin resistance. At week 24, pioglitazone was superior in mitigating depression score (P=0.011). In trend analysis, the effect of time (P<0.001) and group (P=0.023) as well as the time by group interaction (P=0.032) on the mean depression score was considerable. In contrast, significant decrements in anxiety and stress levels (P<0.001 and P=0.012, resp.) were comparable between two groups. With respect to our findings, alterations in depression severity were not correlated with changes in insulin resistance level (P=0.145). In conclusion, our findings suggest that pioglitazone might be able to improve mood in nondiabetic insulin resistant patients. (Registered at Australian New Zealand Clinical Trials Registry; ACTRN12611000351910.)

OBJECTIVE: This study aimed to evaluate the efficacy and safety of N-acetylcysteine, a glutamate-modulating agent, in patients with treatment-refractory obsessive-compulsive disorder as an adjunct to serotonin reuptake inhibitor treatment.METHODS: Forty-eight patients (36 women; mean ± SD age, 30.93 ± 4.99) with obsessive-compulsive disorder who failed to respond to a course of serotonin reuptake inhibitor treatment were randomized to a 12-week intervention period of N-acetylcysteine (up to 2400 mg/d) or placebo. Primary outcome measures were the change in Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score from baseline to end point and the rate of full response in each group at the end of trial. Full response was defined as 35% or greater reduction in Y-BOCS score from baseline.RESULTS: Changes of Y-BOCS score were different over time (P < 0.001) and between groups (P < 0.001). N-acetylcysteine-assigned patients showed significantly improved mean Y-BOCS score (P = 0.003) and Clinical Global Impression-Severity of Illness scale score (P = 0.01) but not Clinical Global Impression-Improvement scale score at study end point. Of the patients in the N-acetylcysteine group, 52.6% were full responders at the end of the study, which was significantly higher than 15% of the patients in the placebo group (P = 0.013).CONCLUSION: This trial suggests that N-acetylcysteine may be a safe and effective option to augment standard treatment in patients with refractory obsessive-compulsive disorder.

The literature is inconsistent as to how coffee affects metabolic syndrome (MetS), and which bioactive compounds are responsible for its metabolic effects. This study aimed to evaluate the effects of unfiltered coffee on diet-induced MetS and investigate whether or not phenolic acids and trigonelline are the main bioactive compounds in coffee. Twenty-four male Sprague‒Dawley rats were fed a high-fat (35% W/W) diet plus 20% W/W fructose in drinking water for 14 weeks, and were randomized into three groups: control, coffee, or nutraceuticals (5-O-caffeoylquinic acid, caffeic acid, and trigonelline). Coffee or nutraceuticals were provided in drinking water at a dosage equal to 4 cups/day in a human. Compared to the controls, total food intake (p = 0.023) and mean body weight at endpoint (p = 0.016) and estimated average plasma glucose (p = 0.041) were lower only in the coffee group. Surrogate measures of insulin resistance including the overall fasting insulin (p = 0.010), endpoint HOMA-IR (p = 0.022), and oral glucose tolerance (p = 0.029) were improved in the coffee group. Circulating triglyceride levels were lower (p = 0.010), and histopathological and quantitative (p = 0.010) measurements indicated lower grades of liver steatosis compared to controls after long-term coffee consumption. In conclusion, a combination of phenolic acids and trigonelline was not as effective as coffee per se in improving the components of the MetS. This points to the role of other coffee chemicals and a potential synergism between compounds.

AIM We tested the hypothesis that crosstalk between cardiomyocyte-rich perivascular tissue (PVT) and coronary arteries is altered in diabetes. METHODS We studied the vasoactive effects of PVT in arteries from the Zucker Diabetic Fatty (ZDF) rat model of type 2 diabetes, streptozotocin (STZ)-treated Wistar rats with type 1 diabetes, and corresponding - heterozygous Zucker Lean (ZL) or vehicle-treated Wistar - control rats. Vasocontractile and vasorelaxant functions of coronary septal arteries with and without PVT were investigated using wire myography. RESULTS After careful removal of PVT, vasoconstriction in response to serotonin and thromboxane analogue U46619 was similar in arteries from ZDF and ZL rats, whereas depolarization-induced vasoconstriction - caused by elevating extracellular [K+ ] - was reduced in arteries from ZDF compared to ZL rats. PVT inhibited serotonin-, U46619- and depolarization-induced vasoconstriction in arteries from ZL rats, but this anticontractile influence of PVT was attenuated in arteries from ZDF rats. Methacholine-induced vasorelaxation was smaller in arteries from ZDF than ZL rats both with and without PVT, and the antirelaxant influence of PVT was comparable between arteries from ZDF and ZL rats. We observed no differences in vasoconstriction, vasorelaxation or PVT-dependent vasoactive effects between arteries from STZ- and vehicle-treated Wistar rats. CONCLUSION Anticontractile influences of PVT are attenuated in coronary arteries from ZDF rats but unaffected in arteries from STZ-treated rats. Signs of endothelial dysfunction are evident in coronary septal arteries - with and without PVT - from ZDF rats but not STZ-treated rats. We propose that altered signalling between cardiomyocyte-rich PVT and coronary arteries can contribute to cardiovascular complications in type 2 diabetes mellitus.

Obesity is associated with chronic disorders like coronary artery diseases, metabolic syndrome, cancers, and psychiatric disorders. Stress may contribute to weight gain by disrupting weight concern, and lead to uncontrolled eating behavior. This study aimed to investigate the effects of stress on weight concern and control behaviors in normal weight and obese adults.A total of 9544 subjects were selected by multi-stage random sampling from three provinces in central Iran. Information related to weight concern and control behavior was registered in normal weight and obese participants. Psychological distress was measured by a 12-item General Health Questionnaire (GHQ-12) and subjects were divided into high and low stress groups. Logistic regression was used for analysis.The mean age of participants was 38.7 ± 15.5 years and 50% (4772) of them were males. The adjusted odds ratio (OR) for age, sex and education of high stress to low stress level for weight concern, weight control behavior and acceptable physical activity behavior was more than 1; but the OR was less than 1 for waist circumference, obesity and healthy diet behavior. Among obese participants, higher levels of stress were associated with lower weight concern with OR, 95%CI: 0.821, (0.682 - 0.988), lower acceptable physical activity with OR = 0.833, 95%CI: (0.624 - 0.912), but higher rates of healthy diet behavior with OR = 1.360, 95% CI: (1.040 - 1.780).Individuals with high stress level have lower weight concern and lower physical activity; therefore, they are prone to weight gain and obesity. It could be concluded that stress management should be considered as a crucial component of obesity prevention and control programs.

Objectives The present study aimed to investigate the incidence and predictors of hypertension in an Iranian adult population. Methods Isfahan Cohort Study was a longitudinal population-based study that was conducted on adults aged 35 years or older, living in urban and rural areas of three districts in central Iran. After 7 years of follow-up, 3283 participants were re-evaluated using a standard protocol similar to the baseline. At both measurements, participants underwent medical interview, physical examination, and fasting blood measurements. Participants (n = 833) with prevalent hypertension were excluded from the analysis, resulting in a sample size of 2450. Results The participants' age was 47.3 ± 9.4 years (mean ± SD) and 50.7% were men. During the follow-up period, 542 (22.1%) individuals developed hypertension, 49.6% of whom were aware of their disease, 42.4% were treated, but only 24.9% were controlled. Incidence rates have shown no sex-specific difference across age and blood pressure (BP) categories. Multivariate-adjusted model controlled for all study covariates showed that age, male sex, general and central obesity, hypertriglyceridemia, impaired fasting glucose, diabetes mellitus, baseline BP at least 120/80 mmHg (nonoptimal BP), and parental history of hypertension independently contributed to the development of hypertension. Higher education level and more than 10% decrease in waist circumference over 7-year follow-up represented protective effects. In men, weight loss decreased and weight gain increased the risk of developing hypertension. Nonoptimal BP along with central obesity and hypertriglyceridemia together were responsible for 71% of the burden of hypertension. Conclusion Our findings imply that there are other factors in addition to nonoptimal BP that deserve integrating into the risk assessment criteria for developing hypertension.

Background. Several remedial modalities for the treatment of tinnitus have been proposed, but an effective standard treatment is still to be confirmed. In the present study, we aimed to evaluate the effect of low-level laser therapy on tinnitus accompanied by noise-induced hearing loss.Methods. This was a double-blind randomized clinical trial on subjects suffering from tinnitus accompanied by noise-induced hearing loss. The study intervention was 20 sessions of low-level laser therapy every other day, 20 minutes each session. Tinnitus was assessed by three methods (visual analog scale, tinnitus handicap inventory, and tinnitus loudness) at baseline, immediately and 3 months after the intervention.Results. All subjects were male workers with age range of 30–51 years. The mean tinnitus duration was1.85±0.78years. All three measurement methods have shown improved values after laser therapy compared with the placebo both immediately and 3 months after treatment. Laser therapy revealed a U-shaped efficacy throughout the course of follow-up. Nonresponse rate of the intervention was 57% and 70% in the two assessment time points, respectively.Conclusion. This study found low-level laser therapy to be effective in alleviating tinnitus in patients with noise-induced hearing loss, although this effect has faded after 3 months of follow-up. This trial is registered with the Australian New Zealand clinical trials registry with identifierACTRN12612000455864).

Opium dependence is a recognized individual and public health threat, but little is known about its association with acute myocardial infarction (AMI) or sudden cardiac death (SCD).In a cross-sectional study followed by a one-year matched longitudinal cohort, all 569 men hospitalized with AMI in all Cardiac Care Units (CCU) of Isfahan, Iran, were recruited in a six-month period. In addition, 123 out-of-hospital deaths were included that were diagnosed as SCD at the same duration. Among those discharged alive, 126 opium dependents were matched with 126 nondependents (mostly nonusers) according to age and smoking status, and were followed for one year. Opium dependence was measured using the ICD10 criteria and Severity of Dependence Scale (SDS) questionnaire. The method was validated by morphine blood levels. Biochemical measurements, blood pressure, blood cell counts, anthropometrics, and ejection fraction were measured at baseline and repeated at the end of follow-up. There were 118 (17.1%) patients with an average of 17.4 ± 10.4 years of abuse who met the criteria for opium dependency. Opium dependence decreased the age at event by 3.6 (95% CI: 1.2 - 6.0) years and was independent of smoking (P = 0.003). In terms of cardiovascular risk factors such as ejection fraction, in addition to post-AMI mortality and morbidity, no significant associations were noted at baseline or after one year of follow-up. The odds ratio of sustained smoking after AMI was 1.92 (95% CI: 1.04 - 3.52) in opium dependents (P = 0.033).Despite public opinion, opium did not improve cardiovascular risk factors, or post-AMI mortality and morbidity. Conversely, there were irrefutable findings regarding the detrimental effects of opium dependence.

The present trial aimed to investigate the effects of pioglitazone on the serum level of asymmetric dimethylarginine (ADMA), a marker of endothelial function, and some indices of inflammation and glucose and lipid metabolism in nondiabetic metabolic syndrome patients. 104 eligible participants (57% female; age between 20 and 70) were enrolled in a double-blind placebo-controlled trial and were randomized to receive either pioglitazone (uptitrated to 30 mg/day) or matching placebo for 24 weeks. Participants were clinically examined and a blood sample was obtained at baseline and at the end of the trial. Pioglitazone significantly improved C-reactive protein level irrespective of changes in insulin sensitivity. Compared with the placebo group, alanine and aspartate transaminases were decreased and high-density lipoprotein cholesterol was increased after treatment with pioglitazone. A considerably greater weight gain was also recorded in the intervention group. We failed to observe any significant changes in serum ADMA in either group and between groups with and without adjustment for age, sex, and components of the metabolic syndrome. In a nutshell, pioglitazone seems to have positive effects on lipid profile, liver transaminases, and systemic inflammation. However, its previously demonstrated endothelial function-improving properties do not seem to be mediated by ADMA.

Background: An association of eating disorder with diabetes mellitus may lead to a serious lack of metabolic control, higher mortality and morbidity. There is no recent study conducted in the Iranian population about eating disorder and its variants. The aim of the present study is investigation of frequency of disturbed eating behaviors in adolescent girls with type 1 diabetes mellitus (T1DM) compared to non-diabetics. Materials and Methods: In this cross-sectional study, disturbed eating behavior were evaluated and compared in two groups of 12–22 year old adolescent and young females (126 with diabetes and 325 without diabetes). A self-report questionnaire including demographic data, Children’s Depression Inventory (CDI), and Eating Attitude Test (EAT-26) was used for data gathering. Independent t -test, Chi-square test, and logistic regression [odds ratio (OR)] were used for data analyses in SPSS 15. Results: Findings revealed that higher percentage of diabetic girls are likely to have eating disturbances (67.9% vs. 53.8%, P = 0.01). Diabetic group obtained higher scores in both dieting (14.95 ± 6.28 vs. 11.79 ± 5.62, P < 0.001) and bulimia scales (4.9 ± 3.13 vs. 4.12 ± 2.89, P = 0.017), which supports a role for T1DM in inducing the symptoms. Diabetic girls were at more than double the risk of developing eating disturbance. Conclusions: The results indicate that a significantly higher percentage of diabetic girls are likely to have eating disturbances. Also, diabetic subjects had an increased probability of getting higher scores in all three EAT-26 subscales. Therefore, healthcare professionals, especially diabetic nurses, should be aware of the potential effects of the subclinical and clinical eating behaviors on adolescents with T1DM and evaluate them for these disturbances.