Quantitative perfusion and water transport time model from multi b-value diffusion magnetic resonance imaging validated against neutron capture microspheres.

Intravoxel Incoherent Motion (IVIM) is a non-contrast magnetic resonance imaging diffusion-based scan that uses a multitude of b-values to measure various speeds of molecular perfusion and diffusion, sidestepping inaccuracy of arterial input functions or bolus kinetics in quantitative imaging. We test a new method of IVIM quantification and compare our values to reference standard neutron capture microspheres across normocapnia, CO2 induced hypercapnia, and middle cerebral artery occlusion in a controlled animal model. Perfusion quantification in ml/100g/min compared to microsphere perfusion uses the 3D gaussian probability distribution and defined water transport time as when 50% of the molecules remain in the tissue of interest. Perfusion, water transport time, and infarct volume was compared to reference standards. Simulations were studied to suppress non-specific cerebrospinal fluid (CSF). Linear regression analysis of quantitative perfusion returned correlation (slope = .55, intercept = 52.5, $R^2$= .64). Linear regression for water transport time asymmetry in infarcted tissue was excellent (slope = .59, intercept = .3, $R^2$ = .93). Strong linear agreement also was found for infarct volume (slope = 1.01, $R^2$= .79). Simulation of CSF suppression via inversion recovery returned blood signal reduced by 82% from combined T1 and T2 effects. Intra-physiologic state comparison of perfusion shows potential partial volume effects which require further study especially in disease states. The accuracy and sensitivity of IVIM provides evidence that observed signal changes reflect cytotoxic edema and tissue perfusion. Partial volume contamination of CSF may be better removed during post-processing rather than with inversion recovery to avoid artificial loss of blood signal.

Treatment of post-radioactive iodine relapse of hyperthyroidism: comparison of long-term methimazole and radioactive iodine treatment.

BACKGROUND: This study aimed to compare the time to achieve euthyroidism and sustained control of hyperthyroidism after treatment with radioactive iodine (RAI) or long-term methimazole (LT-MMI) in patients with post-RAI relapsed hyperthyroidism. METHODS: Sixty four patients with recurrence of hyperthyroidism after RAI treatment were randomly assigned to either RAI or LT-MMI treatment. Both groups were followed every 1-3 months in the first year and then every 6 months for a total of 60 months. RESULTS: In RAI and LT-MMI groups, mean age was 49.0 ± 12.1 and 50.1 ± 14.6 years and time of relapse of hyperthyroidism after previous RAI treatment was 23.2 ± 18.8 and 20.8 ± 17.1 months, respectively. At the end of study, in the LT-MMI group, 31 (97%) and 1 (3%) were euthyroid and hypothyroid, respectively; in the RAI group, 8 (25%) patients were euthyroid, whereas 18 (56%), 3 (9.5%) and 3 (9.5%) had overt hypothyroidism, subclinical hypothyroidism and hyperthyroidism, respectively. Mean time to euthyroidism was 9.4 ± 5.0 months in the RAI group and 3.5 ± 2.8 months in the LT-MMI group (p < 0.001). Patients in the RAI group spent 77.7 ± 14.0 percent and those in the LT-MMI group spent 95.2 ± 5.9 percent of 60 months in the euthyroid state (p < 0.001). CONCLUSION: In patients with post-RAI relapse of hyperthyroidism, LT-MMI treatment was superior to radioiodine because of faster achievement of euthyroidism and more sustained control of hyperthyroidism during 60 months of follow-up.

Sex-specific incidence rates and risk factors of insulin resistance and ß-cell dysfunction: a decade follow-up in a Middle Eastern population.

AIMS: To examine the incidence of and risk factors for insulin resistance and ß-cell dysfunction in a representative Iranian population over a median follow-up of 9.2 years. METHODS: In total, 3662 people (1528 men) without known diabetes with a baseline homeostasis model assessment of insulin resistance (HOMA-IR) level < 75th percentile and, when ß-cell dysfunction was the outcome of interest, 3664 people (1530 men) with a homeostasis model assessment of ß-cell function (HOMA-ß) level ≥ 25th percentile were included in the study (HOMA-IR < 2.20 and HOMA-ß ≥ 64.3 among men, and HOMA-IR < 2.39 and HOMA-ß ≥ 81.7 among women). RESULTS: The incidence rates of insulin resistance and ß-cell dysfunction were 56.3 and 33.6/1000 person-years among men and 48.6 and 50.3/1000 person-years among women, respectively. Applying multivariable Cox regression in both sexes, fasting insulin, triglyceride/HDL cholesterol ratio and lower education were positive predictors of insulin resistance, whereas age was a negative predictor. Moreover, fasting plasma glucose, waist-to-height ratio, wrist circumference and lower hip circumference were significantly associated with incident insulin resistance only among women (all P < 0.05). Considering ß-cell dysfunction in both sexes, age and fasting plasma glucose increased the risk, whereas 2-h post-challenge plasma glucose was a positive predictor only among men, and waist-to-height ratio and triglyceride/HDL cholesterol ratio were negative predictors only among women (all P < 0.05). CONCLUSIONS: Modifiable risk factors are related to the incidence of insulin resistance and ß-cell dysfunction, which can be prevented with proper strategies although the difference between men and women should be taken into account.

Pre-diabetes tsunami: incidence rates and risk factors of pre-diabetes and its different phenotypes over 9 years of follow-up.

AIMS: To investigate the incidence of pre-diabetes and its different phenotypes and the related risk factors during 9 years of follow-up. METHODS: A total of 5879 people (2597 men and 3282 women) aged ≥ 20 years, free of diabetes and pre-diabetes, took part in the study. Multivariable Cox proportional hazard models were used to evaluate hazard ratios (HR) and 95% confidence intervals (CI) for all potential risk factors. RESULTS: Overall, 853 men and 902 women developed pre-diabetes. Incidence rates of pre-diabetes were 46.1 per 1000 person-years in men and 36.8 per 1000 person-years in women, while isolated impaired fasting glucose had the highest incidence rate among all pre-diabetes phenotypes. In both sexes, age, family history of diabetes, fasting plasma glucose and 2-hour post-challenge plasma glucose were related to incident pre-diabetes. Among women, waist-to-height ratio [HR: 1.02 (1.00-1.03)] and being divorced/widowed compared with married [HR: 0.67 (0.52-0.87)] were significant predictors of pre-diabetes; whereas among men, community-based intervention [HR: 0.79 (0.68-0.90)], higher level of education and being single [HR: 0.77 (0.6-0.97)] were protective against progression to pre-diabetes. Moreover, hip circumference among women [HR: 0.95 (0.93-0.98)] and current smoking among men [HR: 1.69 (1.15-2.48)] were related to incident combined impaired fasting glucose and impaired glucose tolerance. CONCLUSION: More than 4% of the Iranian population develop pre-diabetes each year, emphasizing the important role of socio-economic factors (marital status, education and smoking habits) and community-based intervention in progression to impaired glucose regulations. Thus, emergent intervention is necessary to halt the tsunami of pre-diabetes among the Iranian population.

Non-linear association between 25-hydroxyvitamin D and the incidence of type 2 diabetes: a community-based nested case-control study.

AIMS: To examine the nature of the association between 25-hydroxyvitamin D [25(OH)D] and newly diagnosed type 2 diabetes. METHODS: Serum 25(OH)D concentrations were measured for 761 participants (aged 20-83 years) in the Tehran Lipid and Glucose Study, selected for a 1-to-3 nested case-control study. Cases were 191 cases of Type 2 diabetes diagnosed during a median follow-up of 3.6 years. A total of 570 participants were matched with these cases with regard to age, sex, BMI, and month of entering the study. Diabetes was defined according to the American Diabetes Association criteria, 2003. Serum 25(OH)D was measured using the enzyme immunoassay method. Odds ratios for Type 2 diabetes were obtained from conditional logistic regression models for tertiles of serum 25(OH)D concentrations [tertile-1: 2.82-11.02 (reference), tertile-2: 11.03-21.80, and tertile-3: ≥ 21.82 ng/ml]. The multivariate model was adjusted for age, sex, family history of diabetes, systolic blood pressure, triglyceride-to- HDL cholesterol ratio, waist-to-height ratio, lifestyle modification intervention, leisure time physical activity, and fasting plasma glucose at baseline. Non-linearity in the associations between baseline 25(OH)D and Type 2 diabetes, was examined by using restricted cubic splines. RESULTS: Unadjusted odds ratios (95% confidence intervals) of diabetes were 0.73 (0.74-1.13), 0.54 (0.34-0.85) for the second and third tertiles, respectively. Multivariate adjusted odds ratios were 0.47 (0.25-0.90) and 0.43 (0.23-0.82), respectively. Below the cutoff of ~ 10 ng/ml the risk of newly diagnosed Type 2 diabetes increased dramatically. DISCUSSION: It was found that 25(OH)D concentrations contributed to the Type 2 diabetes incidence rate in a non-linear fashion, with the risk beginning to increase sharply for values < 10 ng/ml.

Effects of administration of iron, iodine and simultaneous iron-plus-iodine on the thyroid hormone profile in iron-deficient adolescent Iranian girls.

OBJECTIVE: To investigate whether iron supplementation can improve thyroid hormone function in iron-deficient adolescent girls. DESIGN: A double-blind randomized intervention study. SETTING: The study was performed from 2002 through 2003 in the Islamic Republic of Iran. SUBJECTS: 103 iron-deficient non-anaemic girls who fulfilled all inclusion criteria were included, and 94 subjects successfully completed the study. INTERVENTIONS: Patients were randomly assigned to one of four groups and treated with a single oral dose of 190 mg iodine plus 300 mg ferrous sulphate 5 times/week (n=24), 300 mg ferrous sulphate 5 times/week (n=23), a single oral dose of 190 mg iodine (n=25), or a placebo (n=22) for 12 weeks. RESULTS: All groups were comparable at baseline. After the intervention, there was a significant increase in ferritin and transferrin saturation in the iron+iodine group (17.6 vs 8.7 microg/dl, and 18.8 vs 7.2%, respectively, P<0.001 for both) and in the iron group (P<0.001 for both). Urinary iodine doubled in the iron+iodine group and in the iodine group (P<0.001 for both). Thyroid indices tT4, tT3 and T3RU increased and reverse RT3 decreased in the iron+iodine group (10 vs 8.9 microg/dl, P< 0.001; 143 vs 138 microg/dl, P<0.05; 32.3 vs 28.4%, P<0.001 and 24.8 vs 44.2 ng/dl, P<0.001, respectively) and in the iron group. These two groups did not differ for any of the four indices, but both differed significantly from the iodine and placebo groups. CONCLUSIONS: Our results indicate that improvement of iron status was accompanied by an improvement in some indices of thyroid hormones. SPONSORSHIP: This study was supported by the Dean of Research Affairs of the Tehran University of Medical Sciences.

Effect of L-carnitine on plasma glycemic and lipidemic profile in patients with type II diabetes mellitus.

OBJECTIVE: We designed this study to investigate the effects of oral L-carnitine administration on fasting plasma glucose (FPG), glycosylated hemoglobin (HbA1c) and lipid parameters in patients with diabetes mellitus type II. PATIENTS AND METHODS: The effect of L-carnitine on FPG and lipid parameters was investigated in 22 male and 13 female type II diabetic patients; the mean age +/- s.d. was 51.3 +/- 3.7 y. The patients were randomly allocated to two groups (L-carnitine and placebo group) and 1 g of L-carnitine or of placebo was given orally three times a day for a period of 12 weeks. RESULTS: FPG in the L-carnitine group decreased significantly from 143 +/- 35 to 130 +/- 33 mg/dl (P = 0.03), and we observed a significant increase of triglycerides (TG) from 196+/-61 to 233+/-12 mg/dl (P = 0.05), of Apo A1 from 94 +/- 20 to 103 +/- 23 mg/dl (P = 0.02), and of Apo B100 from 98 +/- 18 to 108 +/- 22 mg/dl (P = 0.02) after 12 weeks of treatment. There was no significant change in LDL-C, HDL-C, HbA1C, LP(a) or total cholesterol. CONCLUSION: L-Carnitine significantly lowers FPG but increases fasting triglyceride in type II diabetic patients.

Cardiovascular risk factors in an Iranian urban population: Tehran lipid and glucose study (phase 1).

OBJECTIVES: Coronary artery disease is becoming more prevalent in developing countries, particularly in urban areas. This study was conducted to determine the prevalence of cardiovascular risk factors among Tehran urban population. METHODS: The prevalence and distribution of high blood pressure, cigarette smoking, dyslipoproteinemia, diabetes mellitus, and obesity was determined in 15,005 subjects, aged three years and over, selected by cluster random sampling in Tehran urban district-13 between February 1999 to August 2001. Total energy intake, percent of energy derived from protein, carbohydrate, and fat were assessed in a subsidiary of 1,474 persons by means of two 24-hour dietary recalls. RESULTS: In adults, 78% of men and 80% of women presented at least one CVD risk factor. The percentage of adult women with two or more risk factors was significantly greater than the one for men. Prevalence of DM, hypertension, obesity, high TC, low HDL, high TGs, and smoking was 9.8, 20.4, 14.4, 19.3, 32, 5.3, and 22.3%, respectively. In children and adolescents, two or more CVD risk factors were found in 9% of boys and 7% of girls. Prevalence of hypertension, obesity, high TC, low HDL, and high TGs, was 12.7, 5.2, 5.1, 10.2, and 5%, respectively. The mean percentage values of energy intake derived from carbohydrate, protein, and fat were 57.8 +/- 6.9, 11.1 +/- 1.8, and 30.9 +/- 7.2, respectively. CONCLUSION: The prevalence of cardiovascular risk factors among Tehran urban population is high; particularly of high total cholesterol, low HDL cholesterol levels, and high waist to hip ratio. An effective strategy for life style modification is a cornerstone of a population approach to the cardiovascular risk factors. Moreover, these results will serve as a baseline for assessment of future trends in the risk factors studied.