Development and validation of a risk score for diabetic kidney disease prediction in type 2 diabetes patients: a machine learning approach.

PURPOSE: This study aims to develop and validate a risk score to predict the occurrence of DKD in individuals with type 2 diabetes using a machine learning (ML) approach. METHODS: By implementing Recursive Feature Elimination with Cross-Validation (RFECV) and RFE on the Diabetes Clinic of Imam Khomeini Hospital Complex (IKHC) dataset, the most critical features were identified. These features were used in the multivariate logistic regression (LR) analysis, and the discrimination and calibration of the model were evaluated. Finally, external validation of the model was assessed. RESULTS: The development dataset included 1907 type 2 diabetic patients, 763 of whom developed DKD over 5 years. The predictive model performed well in the development dataset by implementing RFECV with the RF algorithm and considering six features (AUC: 79%). Using these features, the LR-based risk score indicated appropriate discrimination (AUC: 75.5%, 95% CI 73-78%) and acceptable calibration ([Formula: see text]= 7.44; p value = 0.49). This risk score was then used for 1543 diabetic patients in the validation dataset, including 633 patients with DKD over 5 years. The results showed sufficient discrimination (AUC: 75.8%, 95% CI 73-78%) of the risk score in the validation dataset. CONCLUSIONS: We developed and validated a new risk score for predicting DKD via ML approach, which used common features in the periodic screening of type 2 diabetic patients that are readily available. In addition, a web-based online tool that is readily available to the public was developed to calculate the DKD risk score.

Sitagliptin vs. pioglitazone as add-on treatments in patients with uncontrolled type 2 diabetes on the maximal dose of metformin plus sulfonylurea.

AIMS: To compare the efficacy of sitagliptin versus pioglitazone as add-on drugs in patients with poorly controlled diabetes with metformin and sulfonylureas. METHODS: This is a randomized, open-label, parallel assignment clinical trial. Patients who had inadequate glycemic control [7% (53 mmol/mol) ≤ A1C < 11% (97 mmol/mol)] despite a minimum 6-month period of active treatment with metformin 2000 mg/day plus gliclazide 240 mg/day were enrolled in the study. HbA1C, fasting blood glucose (FBG), fasting plasma lipid parameters [total cholesterol (TC0, low-density lipoprotein cholesterol (LDL-C), triglycerides (TG) and high-density lipoprotein cholesterol (HDL-C)], systolic and diastolic blood pressure (SBP, DBP), weight, waist circumference, and body mass index were measured at baseline and after 17, 34, and 52 weeks of treatment. Generalized estimating equation analysis was done to compare treatment groups for continuous efficacy parameters. RESULTS: No significant difference in HbA1C reduction was observed between the treatment groups during the study course. (P = 0.149, adjusted P = 0.434; coefficient - 0.11 ± 0.08). The FBG (P = 0.032; coefficient 7.44 ± 3.48), HDL-C (P = 0.001; coefficient - 2.69 ± 0.83), TG (P = 0.027; coefficient 12.63 ± 5.71) and SBP (P < 0.001; coefficient 5.43 ± 1.26) changes from baseline, and weight gain were greater in the pioglitazone group. The mean changes in LDL-C and TC from baseline to week 52 were greater in the sitagliptin group (P = 0.034; coefficient - 7.40 ± 3.50, P = 0.013; coefficient - 7.16 ± 2.88, respectively). CONCLUSION: Sitagliptin and pioglitazone were equally effective in improvement of HbA1C. There were some differences in terms of lipid indices, weight gain, and SBP. The current study confirmed that both sitagliptin and pioglitazone are effective treatment options and the decision should be made for each individual based on the baseline characteristics.

Retinal nerve fibre layer thickness is reduced in metabolic syndrome.

AIMS: To investigate retinal nerve fibre layer (RNFL) thickness in people with metabolic syndrome (MetS) and healthy controls. METHODS: A cross-sectional study was performed from March 2014 to January 2016. All participants underwent anthropometric and serological biochemical measurements, ophthalmological examination, and spectral-domain optical coherence tomography (SD-OCT). Individuals with elevated intraocular pressure, glaucoma, diabetic retinopathy and other ocular disorders were excluded. T-test, Chi square and general linear models were used to analyse the data. RESULTS: In total, 278 eyes from 139 participants were investigated [median (interquartile range) age: 37 (32-43) years]. RNFL thickness was lower in the nasal superior (107.8 ± 19.5µm) and temporal superior (135.7 ± 18.9µm) sectors in MetS group compared with the control group (114.6 ± 22.4 µm, P = 0.013 and 140.7 ± 18.2 µm, P = 0.027, respectively). After multiple adjustments for age, gender and the side of the examined [right (OD)/left (OS)] eye, MetS was independently associated with a lower RFNL thickness in the nasal superior (ß = 0.20, P = 0.009) and temporal superior (ß = 0.14, P = 0.048) sectors. RNFL thickness was significantly reduced in participants with higher numbers of metabolic abnormalities, independent of age, gender and the side of the examined eye (P = 0.043). CONCLUSION: Our findings demonstrate that MetS is independently associated with reduced RNFL thickness, suggesting that neurodegeneration is implicated in pathogenesis of MetS.

Vitamin D deficiency is associated with insulin resistance in nondiabetics and reduced insulin production in type 2 diabetics.

It is not known whether the association of serum 25-hydroxyvitamin D [25(OH)D] with glycemic measurements of individuals without diabetes is similar to those with diabetes or not. This study is aimed to investigate the association of serum 25(OH)D with glycemic markers of diabetics, nondiabetics, and prediabetics. A case-control study was conducted on age and sex matched 1,195 patients with type 2 DM, 121 prediabetics, and 209 healthy controls. Anthropometric variables, lipid profile, glycemic measurements, and serum 25(OH)D levels were recorded. Serum insulin and C-peptide levels were also measured. All glycemic measurements were compared between diabetics and nondiabetics and prediabetics at different vitamin D status. Patients with DM had lower serum 25(OH)D compared to prediabetics and healthy controls. Endogenous insulin production in response to food intake and in fasting was significantly lower in vitamin D deficient patients with DM compared to those with serum 25(OH)D>40 ng/ml. Diabetic women with serum 25(OH)D<20 ng/ml had lower beta cell function as estimated by lower HOMA-B compared to their counterparts with serum 25(OH)D>40 ng/ml. Healthy individuals with serum 25(OH)D<20 ng/ml had signs of insulin resistance as estimated by significant increase of HOMA-IR, HbA1c, and fasting plasma glucose (FPG). In addition, we found that serum 25(OH)D was inversely associated with insulin resistance. Vitamin D deficiency is associated with insulin resistance in nondiabetics, which is independent of obesity. Furthermore, vitamin D deficiency is associated with reduced insulin production in type 2 diabetics, which was mainly observed in men. Accordingly, a gender disparity also exists in association of serum 25(OH)D with glycemic measurements.

Comparative effects of metformin and pioglitazone on YKL-40 in type 2 diabetes: a randomized clinical trial.

PURPOSE: Metformin and pioglitazone are believed to exert their long-term benefits by means of amelioration of chronic low-grade inflammation, a key event in development of diabetes and its long-term complications. The present trial was designed to investigate the comparative efficacy of the two anti-diabetes medications on serum concentrations of YKL-40, a novel marker of inflammation. METHODS: In a parallel-group, open-label, randomized trial setting (ClinicalTrials.gov Identifier No. NCT01521624), 84 newly diagnosed, medication-naïve type 2 diabetes patients were assigned to metformin 1,000 mg daily (n = 42) or pioglitazone 30 mg daily (n = 42). Serum concentrations of YKL-40, along with highly sensitive C-reactive protein, indices of glycemic control and lipid profile were measured at baseline and after 3 months. RESULTS: In the analyzed sample (metformin = 40, pioglitazone = 42), both medications were equally effective with regard to control of hyperglycemia, and hsCRP reduction (p > 0.05). However, metformin caused a significant decline in weight (p = 0.005), BMI (p = 0.004), and total cholesterol levels (p = 0.028) of the patients. Metformin also significantly reduced YKL-40 concentrations after 3 months (1.90 ± 17 vs. 1.66 ± 0.15 µg/L, p = 0.019). The amount of change in the pioglitazone arm did not reach statistical significance (2.18 ± 0.14 vs. 2.25 ± 0.16 µg/L, p = 0.687). When compared, metformin was significantly more effective than pioglitazone with respect to YKL-40 reduction in both univariate (p = 0.020, effect size = 6.7%) and multivariate models (p = 0.047, effect size = 5.7%). CONCLUSIONS: Metformin is more effective in reduction of YKL-40 concentration in short term and the effect seems to be independent of degree of glycemic control, or hsCRP reduction.

Gender-dependent effects of metformin on vaspin and adiponectin in type 2 diabetes patients: a randomized clinical trial.

The aim of the study was to assess the effects of metformin on serum concentrations of vaspin and adiponectin in diabetes. Randomized clinical trial of 99 newly diagnosed, medication-naïve, type 2 diabetes patients (NCT01521624) was carried out. Patients were randomly assigned to either metformin 1 000 mg daily plus advice for exercise and lifestyle modification (n=50) or modification alone (n=49). A third group of 50 normoglycemic subjects were also enrolled to compare adipokine concentrations between healthy and diabetes subjects. Serum concentrations of adipokines were measured at baseline and after 12 weeks using ELISA method. Healthy subjects had significantly higher adiponectin levels, but lower concentrations of serum vaspin (p<0.001 in all cases). Vaspin and adiponectin concentrations were 23% and 26% higher in women compared with men. Vaspin dropped significantly after 3-month metformin therapy only in women (1.36 vs. 0.98, p=0.003 in women and 1.31 vs. 1.20, p=0.335 in men). Metformin therapy did not change adiponectin concentration in neither women nor men of the case group (12.66 vs. 12.44 p=0.699 in women and 10.13 vs. 10.94 p=0.253 in men). Comparing case and control groups, metformin decreased vaspin levels more significantly than lifestyle modification in the final multivariate model after controlling for potential confounders only in women (p=0.002) but not men (p=0.896). Conversely, adiponectin levels increased more significantly in the control group, again only in women (p=0.012 and 0.579 for women and men, respectively). Our findings suggest that metformin therapy reduces vaspin concentration in a gender-specific manner. Metformin exerts little benefit in increasing adiponectin levels in diabetes patients.

Comparison of osteoprotegerin and vascular endothelial growth factor in normoalbuminuric Type 1 diabetic and control subjects.

BACKGROUND: The aim of the current study was to evaluate the association of osteoprotegerin and vascular endothelial growth factor (VEGF) with glycemic indices and diabetes status. METHODS: A total of 44 normoalbuminuric Type 1 diabetic patients and 44 healthy control subjects, matched for age, body mass index, sex ratio, and lipid measures were enrolled. Univariate and multivariate logistic regression analyses were used to determine the association of osteoprotegerin and VEGF with diabetes status. Further, linear regression analysis was performed to investigate the roles of osteoprotegerin and VEGF as determinants of glycated hemoglobin (HbA1c). RESULTS: Osteoprotegerin and VEGF were significantly elevated in diabetic subjects (2.76±0.85 vs 2.26±0.75 pmol/l and 187.1±92.7 vs 125.9±52.3 pg/ml, respectively, p<0.01) and were positively correlated with glycemic indices (i.e. fasting plasma glucose and HbA1c, p<0.001). After controlling for possible confounding factors, odds ratios (confidence interval) of osteoprotegerin and VEGF for diabetes were 2.532 (1.003-6.392) and 1.021 (1.002-1.041), respectively (p<0.05). Further, linear regression analysis revealed that the association of osteoprotegerin with HbA1c is independent of VEGF and vice versa (p<0.001). CONCLUSION: Osteoprotegerin and VEGF are elevated in normoalbuminuric Type 1 diabetic subjects and are independently associated with glycemic indices and diabetes status.

The effect of coenzyme Q10 supplementation on metabolic status of type 2 diabetic patients.

AIM: Increased oxidative stress and impaired antioxidant defense contribute to pathogenesis and progression of type 2 diabetes. Consistent with this fact, it has been shown that diabetic patients have reduced coenzyme Q10 level. In this study we sought to compare the effect of coenzyme Q10 versus placebo on glycemic control and lipid profile in type 2 diabetic patients. METHODS: In a randomized double-blind placebo-controlled trial, 64 type 2 diabetic patients were randomly assigned to receive either 200 mg Q10 or placebo daily for 12 weeks. Fasting blood samples were obtained and fasting plasma glucose (FPG), HbA1c, total cholesterol (TC), triglycerides (TG), LDL-C and HDL-C were measured. RESULTS: In this study no significant differences considering age, body mass index (BMI), diabetes duration, FPG, HbA1c, TC, TG, LDL-C and HDL-C were shown between two groups. Serum HbA1C concentration decreased in the Q10 treated group (8 ± 2.28 vs. 8.61 ± 2.47%) with no significant effect in the placebo group. Following intervention no differences have been shown regarding FPG, TG and HDL-C in Q10 treated group. Furthermore, mean differences of TC and LDL-C level were statistically altered between two groups (P value=0.027 and 0.039 respectively). CONCLUSION: In this study, Q10 treatment improved glycemic control, total and LDL cholesterol but these differences were associated with no favourable effects on TG and HDL-C.

Hepatitis B vaccination coverage among Iranian children aged 15-26 months in 2006.

This study in 2006 estimated the hepatitis B virus (BHV) vaccination coverage in the Islamic Republic of Iran at the national and district levels in urban, rural and remote populations of 41 university health service areas. Of 21 905 children recruited to the study, vaccination coverage based on vaccination card records was 100% in 14, 15 and 10 of the 41 university areas for the 1st, 2nd and 3rd doses of HBV respectively. National levels of HBV1, HBV2 and HBV3 coverage were 98.9%, 98.8% and 98.4% respectively. The lowest HBV vaccination coverage rate was 90.7% (in a remote district). HBV vaccination coverage was at an acceptable level in Iranian children.

Trends of diabetes according to body mass index levels in Iran: results of the national Surveys of Risk Factors of Non-Communicable Diseases (1999-2007).

AIMS: The prevalence of diabetes is increasing dramatically worldwide. Less is known about whether this trend is similar among obese and lean individuals. METHODS: We analysed the data sets of three cross-sectional national surveys in adults aged 25-64 years: the National Health Survey-1999 (n=21,576), and the national Surveys of Risk Factors of Non-Communicable Diseases (SuRFNCD)-2005 (n=70,981) and SuRFNCD-2007 (n=4233). Diagnosed diabetes was ascertained, and height and weight were measured in all surveys. In SuRFNCD-2005 and SuRFNCD-2007, fasting plasma glucose was used to identify subjects with newly diagnosed diabetes (≥ 7 mmol/l) and impaired fasting glucose (5.6 - 6.9 mmol/l) among individuals not reporting diabetes. RESULTS: The prevalence of diagnosed diabetes (after adjustment for age, sex and residential area) was 2.5, 4.0 and 4.6% in 1999, 2005 and 2007, respectively. The total prevalence of diabetes increased from 7.7% in 2005 to 8.7% in 2007, about half of which was attributed to newly diagnosed disease (in both surveys). The prevalence of diabetes increased in all categories of obesity, with the most evident trend being among subjects with body mass index <25 kg/m(2) . CONCLUSIONS: The prevalence of diabetes among Iranian adults has increased more than 1.8-fold in a period of only 8 years since 1999. This is the first report from Iran, and urgent measures need to be taken in order to prevent the progression and worsening of the problem and emergence of its undesired consequences.

The economic costs of diabetes: a population-based study in Tehran, Iran.

AIM/HYPOTHESIS: The aim of the study was to determine the annual healthcare expenditures of an individual with diabetes in Tehran, between March 2004 and March 2005. METHODS: This prevalence-based 'cost-of-illness' study was conducted in two phases. In the first phase, 23,707 randomly selected individuals were interviewed to gather a cohort of participants with diabetes. In the second phase, 710 diabetic patients and 904 age- and sex-matched controls were followed up for 1 year at intervals of 3 months and the direct (physician services, medications and devices, hospitalisation, laboratory, paraclinical and transport) and indirect (loss of productivity) expenditures were recorded. The excess costs of a person with diabetes were estimated through comparison with matched controls. The estimates were also extrapolated to the total population of Tehran and Iran. The costs were converted from the Iranian rial to the US dollar (exchange rate September 2004). RESULTS: Total annual direct costs of diabetic and control participants were $152.3 +/- 14.5 and $52.0 +/- 5.8, respectively, which is indicative of 2.92 times higher costs in diabetic patients. The most expensive components of direct costs were medications and devices, and hospitalisation in diabetic patients (28.7% and 28.6%, respectively). Total indirect costs were $39.6 +/- 2.4 and $16.7 +/- 1.1 in diabetic and non-diabetic individuals. The aggregate annual direct costs of diabetes were estimated to be $112.424 +/- 10.732 million and $590.676 +/- 65.985 million in Tehran and Iran, respectively. Diabetes complications contributed 53% of the aggregate excess direct costs of diabetes. CONCLUSIONS/INTERPRETATION: Diabetes is an expensive medical problem in Iran and planning of national programmes for its control and prevention is necessary.

Insulin resistance is an independent correlate of increased urine albumin excretion: a cross-sectional study in Iranian Type 2 diabetic patients.

AIMS: To assess the association of insulin resistance with increased urinary albumin excretion (UAE) in a cohort of Iranian Type 2 diabetic patients. METHODS: Three hundred and sixty-one men and 472 women with Type 2 diabetes were enrolled from three different outpatient clinics (Tehran, Iran) during the period 2005-2008. Patients with obstructive uropathy, severe heart failure, liver disease, cancer, autoimmune disease and macroalbuminuria were not included. Microalbuminuria (MA; defined as UAE >or= 30 mg/day) was found in 242 (29.1%) patients; 591 (70.9%) subjects had normoalbuminuria (UAE < 30 mg/day). Insulin resistance was assessed using homeostasis model assessment of insulin resistance (HOMA-IR). RESULTS: HOMA-IR index values were higher in subjects with MA than those with normoalbuminuria (P < 0.00001). Adjusted values (for age, sex and duration of diabetes) of UAE and HOMA-IR were 11.81 +/- 7.51 (mg/day) and 3.30 +/- 2.21 in normoalbuminuric and 75.36 +/- 55.57 (mg/day) and 4.98 +/- 3.22 in the MA group, respectively (P < 0.00001 for all). Multiple regression analysis showed that UAE was predicted by HOMA-IR, independently of age, duration of diagnosed diabetes, triglycerides, waist circumference, metabolic control, blood pressure and related treatments (P < 0.00001). When patients were categorized into quartiles of HOMA-IR, those of the fourth quartile (i.e. the most insulin resistant) were at a higher risk of increased UAE than other quartiles [odds ratio (OR) 3.7 (95% confidence intervals 2.7-6.2)]. CONCLUSIONS: In Iranian Type 2 diabetic patients, albuminuria was strongly associated with insulin resistance. HOMA-IR is an independent predictor of UAE.

Distinguishing between primary infection and reinfection with rubella vaccine virus by IgG avidity assay in pregnant women.

During the mass measles/rubella vaccination campaign in 2003 in Iran, many pregnant women were vaccinated mistakenly or became pregnant within 1 month of vaccination. To distinguish pregnant women who were affected by rubella vaccine as primary infection from those who had rubella reinfection from the vaccine, serum samples were collected 1-3 months after the campaign from 812 pregnant women. IgG avidity assay showed that 0.3% of the women had no rubella-specific IgG response; 14.4% had low-avidity anti-rubella IgG and were therefore not immune to rubella before vaccination; 85.3% had high-avidity anti-rubella IgG and were regarded as cases of reinfection.

Prevalence of oropharyngeal colonization by Haemophilus influenzae type b in Iranian children.

Healthy carriers of Haemophilus influenzae type b (Hib) play an important role in the spread of invasive disease. The aim of this study was to assess the need for Hib vaccination in Iranian children by estimating the prevalence of Hib oropharyngeal colonization among children in Tehran. Cultures were prepared from oropharyngeal swabs of 1000 children in 25 day-care centres in Tehran from October 2005 to March 2006. The prevalence of Hib carriers was 7.6%, similar to other developing countries prior to inoculation with the conjugate Hib vaccine. We recommend Hib vaccination be included in the Iranian national programme of immunization.

The Effect of Coenzyme Q10 Supplementation on Circulating Levels of Novel Adipokine Adipolin/CTRP12 in Overweight and Obese Patients with Type 2 Diabetes.

Background: Adipolin, the novel adipokine that is proposed to be reduced in diabetes, obesity and inflammation, may improve glycemic control. It is known that coenzyme Q10 could improve insulin sensitivity. The aim of the current study was to investigate the effect of Q10 supplementation on adipolin concentration and glucose metabolism in overweight and obese diabetic patients. Material & Methods: Sixty four patients with type 2 diabetes and 25

Circulating levels of fibroblast growth factor 21 in early-stage diabetic kidney disease.

AIMS/PURPOSE: Fibroblast growth factor 21 (FGF21), a hepatoadipokine with pleiotropic metabolic regulatory actions, is emerging as a novel biomarker of progressive nephropathy. We sought to evaluate circulating FGF21 and its association with clinical and biochemical characteristics as well as the urinary albumin excretion (UAE) rates in a population of patients with type 2 diabetes (T2D) with or without microalbuminuria and their matched healthy controls. METHODS: Cross-sectionally, 130 consecutive individuals comprising patients with T2D with (n = 44) or without (n = 44) microalbuminuria and their healthy controls (n = 42) were recruited for analysis. Various demographic, clinical and biochemical parameters were assessed. RESULTS: Serum FGF21 levels were significantly elevated in patients with microalbuminuria [median (interquartile range, IQR): 269.50 (188.50) pg/mL] compared to their normoalbuminuric peers with T2D [median (IQR): 103.50 (75.75) pg/mL] and nondiabetic people [median (IQR): 99.00 (126.75) pg/mL]. While serum FGF21, diastolic blood pressure and duration of diabetes mellitus (DDM) were independently associated with microalbuminuria in the baseline logistic regression model, FGF21 and DDM emerged as significant correlates in the multivariate adjusted model (OR for FGF21 = 1.060, 95% CI = 1.011-1.110, P < .016). CONCLUSIONS: Serum FGF21 level is strongly associated with early-stage diabetic kidney disease in the high-risk population of patients with T2D (particularly with circulating FGF21 values rising above 181 pg/mL). The association of serum FGF21 with subclinical stages of diabetic nephropathy may unearth perspectives on early detection and prevention of the advanced stages of chronic diabetes microvascular complications through effective FGF21-targeted therapy.

Fasting hyperinsulinaemia and 2-h glycaemia predict coronary heart disease in patients with type 2 diabetes.

AIM: Patients with diabetes are at greater risk of cardiovascular events. Insulin resistance (IR) and hyperinsulinaemia are both related to an increased cardiovascular risk, but whether IR predicts coronary heart disease (CHD) independently of other risk factors in patients with type 2 diabetes (T2D) is a topic of considerable controversy. The aim of the present study was to evaluate the prospective relationship of fasting insulin, HOMA-IR, fasting plasma glucose (FPG) and 2-h post-load glucose (2hPG) load with CHD incidence among such patients. METHODS: A total of 2607 patients with T2D were enrolled in a community-dwelling cohort and followed for an average of 7.2 years. Conventional CHD risk factors, FPG, 2hPG, fasting insulin levels and HOMA-IR index were measured at baseline. Cox regression hazard ratios (HRs) were used to assess CHD risk. RESULTS: A total of 299 'hard' CHD events were registered (in 114 women and 185 men). Increasing levels of fasting insulinaemia were positively associated with CHD incidence. This correlation persisted after controlling for gender, body mass index, blood pressure, lipid profile, medication use and HbA1c [HR for each increase in quartile (fully adjusted model): 1.18 (95% CI: 1.06-1.32); P<0.01]. 2hPG showed a non-linear association with incident CHD [HR of highest vs lowest quartile: 1.64 (95% CI: 1.03-2.61)]. Fasting glycaemia was not associated with CHD risk, whereas HOMA-IR had a direct and independent correlation with CHD risk [HR for each one-quartile increase: 1.19 (95% CI: 1.07-1.34); P<0.01]. CONCLUSION: Fasting insulin levels are positively associated with incidence of CHD in T2D. Furthermore, 2hPG appears to be a significant predictor of incident CHD independently of other risk factors, including HbA1c. These findings suggest that strategies targeting the reduction of insulinaemia and post-load glycaemia may be useful for preventing cardiovascular complications.

Hypertension and mortality in the Golestan Cohort Study: A prospective study of 50 000 adults in Iran.

High blood pressure has been the second most important determinant of disease burden in Iran since the 1990s. Despite well-recognized evidence on the association of high blood pressure and mortality in other countries, this relationship has not been fully investigated in the demographic setting of Iran. The current study is the first large-scale longitudinal study of this association in Iran. Briefly, 50 045 subjects between 40 and 75 years of age have been recruited and followed. Blood pressure measurements were carried out at baseline. Causes of death were reported and verified by verbal autopsy throughout the follow-up period. The outcomes of interest were all-cause deaths and deaths due to ischemic heart disease (IHD) or stroke. Cox proportional hazards regression models were used to estimate hazard ratios (HRs). A total of 46 674 subjects free from cardiovascular disease at baseline were analyzed. Absolute mortality rates increased along with increasing systolic or diastolic blood pressure above 120 and 80 mm Hg, respectively. Adjusted HRs (95% confidence intervals) for each 20 mm Hg increase in systolic blood pressure in all age groups were 1.18 (1.13-1.23) for all-cause mortality, 1.21 (1.13-1.31) for deaths due to IHD and 1.50 (1.39-1.63) for deaths due to stroke. Unadjusted and adjusted HRs were higher in younger subjects and decreased with increasing age of the participants. High blood pressure is a serious threat to the health of Iranians. The entire health-care system of Iran should be involved in a comprehensive action plan for controlling blood pressure.

Reduction in asymmetric dimethylarginine plasma levels by coenzyme Q10 supplementation in patients with type 2 diabetes mellitus.

AIM: According to many studies, supplementation with Coenzyme Q10 (CoQ10) yields beneficial results in terms of endothelial function in type 2 diabetes mellitus. Despite these promising results, data elucidating the effect of CoQ10 on plasma levels of asymmetric dimethylarginine (ADMA), as a recently discussed cardiovascular risk factor, is lacking. This study was designed to investigate the effect of CoQ10 supplementation on endothelial function, specifically by evaluating plasma ADMA levels. METHODS: Sixty-four type 2 diabetic patients were randomly assigned to two groups; either receiving 200mg/d oral dose of CoQ10 (N.=31) or receiving placebo (N.=33) for 12 weeks. Clinical and biochemical assessments were performed before and after the trial for evaluating ADMA, serum nitrite and nitrate (NOx), hemoglobin A1c and lipid profile. RESULTS: The intervention resulted in a significant improvement in ADMA, NOx , low-density lipoprotein and hemoglobin A1c levels in CoQ10 compared to placebo group. Interestingly, difference in changes of these parameters were also significant (P=0.01, 0.03, 0.04 and 0.03, respectively). CONCLUSION: Supplementation with CoQ10 yields beneficial effects on ADMA levels, leading to decreased diabetic cardiovascular events.