مجله غدد درون ریز و متابولیسم ایران
سال یازدهم شماره 6 (پیاپی 48، اسفند 1388)

Metabolic syndrome is a clustering of metabolic abnormalities that increase the risk of chronic disease such as obesity, cardiovascular disease and diabetes. This study aimed at examing the associations between dietary glycemic index (GI) and glycemic load (GL) intake using the three definition of metabolic syndrome (Mets) and each of their components.

Blood samples and 24-hour dietary recalls were obtained from 120 healthy adults, without Mets or diabetes, aged ≥40 yr, participants of the Tehran Glucose and Lipid study, in the east of Tehran. Anthropometric indices, blood pressure, fasting blood glucose, trygliceride, LDL-cholestrol and HDL-cholestrol were determined and GI and GL were measured in those who developed Mets after six years and results were compared to those subjects without Mets. Mets was defined according to criterias set by ATPIII, WHO and IDF.

After adjustment for potential confounding variables, GI and GL were inversely associated with ATPIII and IDF definitions. After adjustment for confounding lifestyle and dietary factors the prevalence of Mets was significantly higher among those in the highest quintile of GI (OR: 4. 5 95%CI: 1-19. 2) and GL(OR: 4. 8 95%CI: 1. 1-20. 6) compared to those in the lowest quintile category. On the other hand, after controlling for potential confounders, subjects in the highest quintile of GI, had higher LDL-cholestrol (P= 0. 005), body mass index (P=0. 003) and lower HDL-cholestrol (P=0. 01), than did those in the lowest quintile. Highest quintile of GL was associated with higher LDL-cholestrol (P= 0. 001) and lower HDL-Cholestrol (P=0. 015).

Results suggest that GI and GL may have unfavorable effects on metabolic syndrome and its components

The metabolic syndrome is a constellation of risk factors that increase the incidence of cardiovascular disease and type 2 diabetes mellitus. The prevalence of obesity and metabolic syndrome in adolescents is escalating worldwide. Understanding the rising prevalence of this syndrome could help decrease the occurrence of fatal cardiovascular and diabetic complications. The present study was carried out to determine the prevalence of metabolic syndrome in adolescents with varying degrees of obesity, in order to conduct and implement, timely screening and interventions.

In a cross-sectional study conducted within the framework of the Tehran Lipid and Glucose Study (TLGS), phase 3, 1523 adolescents, 708 boys and 815 girls 10-19 years of age, were investigated. The prevalence of metabolic syndrome, based on modified definitions for ATP III, AHA, NHASES III and IDF, was determined in varing degrees of body weight (normal, at risk of overweight, moderate and severe overweight) and compared in different sex, age groups, menarche status and familial history of diabetes mellitus. Data was analyzed using the and Mann-Whitney tests and multiple logistic regression.

Overall, 15 percent of adolescents were at risk of overweight, 4. 2 percent had moderate overweight and 4. 6 percent were severely overweight, with no significant difference between the two sex groups (P=0. 381). Overall, the prevalence of metabolic syndrome, based on definitions for ATP III, AHA, NHANES III and IDF, was 9. 5, 5. 1, 17. 8 and 5. 8 percent, respectively, which was significantly higher in boys than in girls. Based on the 4 defintions, the prevalence of metabolic syndrome in the normal weight group was 2. 2, 0. 9, 8. 6, 0. 8 percent respectively, in the at risk of overweight group it was 21. 5, 11, 36. 4 and 11 percent, in moderate overweight group it was 42. 2, 23. 4, 64. 1 and 32. 8 percent, and in the severe overweight group it was 62. 9, 38. 6, 67. 1 and 47. 1 percent, respectively (P<0. 001). The prevalence of each metabolic risk factor and the number of these factors was higher in overweight adolescents. Only by the IDF definition, the prevalence of metabolic syndrome was significantly higher after-menarche than before it (P=0. 04). All definitions showed the higher prevalence of metabolic syndrome in positive familial history of diabetes mellitus (P<0. 001).

This study showed a high prevalence of overweight, obesity and metabolic syndrome in Tehranian adolescents, with significantly higher prevalence of metabolic syndrome in more obese adolescents. Metabolic syndrome was more prevalent, in boys, thosepersons with positive familial history of diabetes mellitus and in after-menarche aged girls,which data can be put to use in lifestyle modification programs.

Artificial neural networks as a modern modeling method have received considerable attention in recent years. The models are used in prediction and classification in situations where classic statistical models have restricted application when some, or all of their assumptions are met. This study is aimed to compare the ability of neural network models to discriminant analysis and logistic regression models in predicting the metabolic syndrome.

A total of 347 participants from the cohort of the Tehran Lipid and Glucose Study (TLGS) were studied. The subjects were free of metabolic syndrome at baseling according to the ATPIII criteria. Demographic characteristics, history of coronary artery disease, body mass index, waist, LDL, HDL, total cholesterol, triglycerides, fasting and 2 hours blood sugar, smoking, systolic and diastolic blood pressure were measured at baseline. Incidence of metabolic syndrome after about 3 years of follow up was considered a dependent variable. Logistic regression, discriminant analysis and neural network models were fitted to the data. The ability of the models in predicting metabolic syndrome was compared using ROC analysis and the Kappa statistic, for which, MATLAB software was used.

The areas under receiver operating characteristic (ROC) curve for logistic regression, discriminant analysis and artificial neural network models (15: 8: 1) and (15: 10: 10) were estimated as 0. 749, 0. 739, 0. 748 and 0. 890 respectively. Sensitivity of models were calculated as 0. 483, 0. 677, 0. 453 and 0. 863 and their specificity as 0. 857, 0. 660, 0. 910 and 0. 844 respectively. The Kappa statistics for these models were 0. 322, 0. 363, 0. 372 and 0. 712 respectively.

Results of this study indicate that artificial neural network models perform better than classic statistical models in predicting the metabolic syndrome.

Diabetes mellitus is the most common human metabolic disease and chronic non healing diabetic foot ulcers are a critical complication for these patients. ANGIPARS is a new herbal extract which has been introduced to accelerate healing of these ulcers. The purpose of this study was to investigate the efficacy and safety of oral ANGIPARS in patients with chronic diabetic foot ulcers and also its effect on inflammatory blood markers.

In a double–blind placebo-controlled trial, 40 patients with diabetic foot ulcers of at least 4 weeks duration, were randomized to receive either oral ANGIPARS, or placebo twice a day, until the ulcer was completely healed or for a maximum of 6 weeks and followed up to 12 weeks. Standard foot ulcer care was given to all patients. The healing process was assessed with measuring ulcer surface area and time needed to achieve complete wound healing. Drug safety was assessed by monitoring adverse events, using clinical and laboratory evaluations.

In both groups, wound surface area decreased significantly (p<0. 0005). Mean improvement ratio was 95. 8% in the ANGIPARS group and 79. 2% in the placebo group, although mean percent of wound area reduction in the former group was higher than in the placebo group at weekly assessments, this difference was not statistically significant (p= 0. 25) except for at the 4th week. (84/2% vs. 56%, p = 0. 013) Ultimately, complete wound healing was achieved in 90% and 70% of ANGIPARS group and placebo group, respectively, after 12 weeks. Time to achieve complete wound healing, also, was not different significantly in either groups. (6. 2 vs. 7. 4 weeks, p = 0. 3) Significant reduction in ESR was seen in the ANGIPARS group. (p = 0. 04) There was no significant changes in laboratory parameters. Two complications most likely attributable to ANGIPARS reported were worsening of proliferative diabetic retinopathy in one patient and acute renal failure and acute hepatitis in another patient with diabetic nephropathy.

Although ANGIPARS enhanced wound healing at least within weeks 2 to 4 of treatment, we did not observe a significant effect in the outcome. Therefore, standard foot ulcer care seems to be the cornerstone of diabetic foot ulcer management and ANGIPARS should probably be reserved for treatment of the non-healing or difficult-to-heal ulcers that do not respond to standard treatments. Further studies are required to assess the efficacy of this new herbal extract.

Leptin, a hormone secreted by the adipocytes, plays a key role in a feedback loop that maintains energy balance by signaling the state of energy stores to the brain and by influencing the regulation of appetite and energy metabolism. Zinc (Zn) also plays an important role in appetite regulation. It has been shown that Zn deficiency decreases appetite and that Zn supplementation increases it. Our aim is to evaluate the relationship between serum Zn, and leptin in postmenopausal diabetic women.

We studied 45 diabetic women and 45 healthy women (controls) with Body Mass Index (BMI) 25-30 kg/m2 and age 45-60 y. Serum leptin, serum zinc, Tumor Necrosis Factor-α (TNF-α), and Interleukin-6 (IL-6) were determined in diabetic and healthy groups. Comparisons were performed with the t test in diabetic and healthy groups. Linear regression was used to evaluate the relations among different variables in the two groups.

There was a non-significant, negative correlation between serum leptin and zinc in postmenopausal diabetic women (r=-0. 14), and, a non-significant, positive correlation between serum leptin and zinc in postmenopausal healthy women (r= 0. 10). TNF-α and IL-6 have no significant effects on the relationship between serum zinc and leptin in postmenopausal diabetic and healthy women.

There was no significant relationship between serum leptin and zinc in postmenopausal diabetic women. The pathophysiological pathways by which zinc and leptin regulate energy intake and appetite and the detailed mechanism between them need to be further clarified by future studies.

Identification of women at risk of diabetes mellitus a most prevalent disorder in pregnancy, could be useful. This 2009 study investigated whether high maternal Hemoglobin (Hb) level in the first trimester would be associated with Gestational Diabetes Mellitus in women referring to healthcare centers in Tehran.

A case-control was conducted on 60 pregnant women with gestational diabetes (case group) and 61 pregnant women without the condition (control group) referring to healthcare clinics affiliated to the Research Center of Endocrinology and Metabolism of the Ayatolah Taleghani Hospital as well as Iran Research Institute of Endocrinology and Metabolism, selected by convenience sampling. An information form was used for collecting data by interviewing the subjects. Both groups were matched for age, number of abortions and parity.

Demographic characteristics were similar in the two groups. Levels of Hb (>13. 8g/dl) in the case group were higher than in the control group (60% vs. 6. 6%) significant difference between the 2 groups (p=0. 0001) with an estimated odds ratio (OR) 7. 61 (CI 95% = 2. 72 -21. 28).

Findings showed a significant relationship between high maternal Hb and Gestational Diabetes Mellitus. Healthcare workers can use the results of this study to monitor high maternal hemoglobin in the first trimester as a significant risk factor for gestational diabetes. Thus, in selected screening programs for gestational diabetes in terms of risk factors, women should undergo GTT and preventive measures with less time and cost can be taken decrease the complications.

Diabetes mellitus in thalassemic major patients is common. It is usually caused by secondary hemosiderosis but a long period of insulin resistance may be occur before occurrence of overt diabetes. Zinc deficiency, also common in thalassemic patients, it seems aggravates abnormal glucose metabolism in such patients. The aim of this study was to determine serum zinc level and the contributory effect of zinc deficiency on insulin resistance and glucose intolerance in thalassemic patients in Mashhad city.

This descriptive study was conducted on patients with thalassemia major. Patients with diabetes, using medicines that interfere with serum zinc (except of iron chelators) and glucose levels were excluded. Blood samples for assessment of glucose, insulin, zinc, ferretin, albumin, PT, PTT levels were obtained and a standard glucose tolerance test was performed for all patients. Insulin resistance was calculated by the homeostatic model assessment of insulin resistance (HOMA- IR). Complete insulin resistance was defined complete in HOMA-IR>3. 9, partial in HOMA-IR between 2. 5-3. 9 and normal in HOMA-IR<2. 5.

Of the 109 thalassemic patients were enrolled, 4 (3. 66%) patients had impaired glucose tolerance test, 2 (1. 83%) had diabetes and the remaining were normal. The prevalence of zinc deficiency was 38. 5% in our patients. Mean serum zinc level in diabetic patients was 88. 2±2. 9 micgr/dl and in non-diabetic patients was 84. 2±14. 9 (p=0. 34). After exclusion of diabetic patients, insulin resistance was very high in the remaining patients. Of these, 68 (63. 5%) of patients had complete insulin resistance, 31 (28. 9%) had partial resistance and only 8 (7. 47%) had normal insulin sensitivity. No significant difference was found in ferretin levels, age and sex, between diabetic and non- diabetic patients (p=0. 93, 0. 35, 0. 28 respectively). A significant reverse correlation was found between serum zinc level and fasting blood sugar (p=0. 002) and serum ferretin level (p=0. 05). The correlation with other variables was not significant.

Zinc deficiency and insulin resistance are prevalent in thalassemic patients but no association was found between zinc deficiency and occurrence of diabetes in our study population.

The aim of this study was to determine the incidence of thyroid dysfunction and the natural course of subclinical thyroid disorders in the Tehranian community.

All individuals ≥20 years, who participated during the first to third phases (6 years, 7 months), of the "Tehran Lipid and Glucose Study" and provided the relevant data were included in this study. Both Tpo-Ab and TSH were measured. In 808 TPO-Ab negative individuals who were not taking any thyroid & anti-thyroid drugs and without a history of thyroid disease, thyroid surgery, goiter and thyroid nodules, mean, median, 2.5, 5, 95, 97.5 percentile TSH were determined. On the basis of 2.5 and 97.5 percentile, normal reference range for TSH was 0.4-5.8 μu/mL. In those, whose TSH fell outside the reference range, T3, T4, and T3 uptake were measured and FTI was calculated.

In the first stage, 1065 women and 693 men had normal thyroid tests. After 6.7 years the incidence of clinical hypothyroidism was 0.28 in 1000 women and 0. 21 in 1000 men, subclinical hypothyroidism was 11.59 in 1000 women and 4. 69 in 1000 men, clinical hyperthyroidism was 1.4 in 1000 women and 0.21 in 1000 men, subclinical hyperthyroidism was 5.72 in 1000 women and 3.62 in 1000 men. In this period, increasing positivity of TPO-Ab from 15.9 to 17.7% in women was significant. (P=0.006) In the first stage 8 women had subclinical hypothyroidism, 5 still did on follow-up, one was normal, and one was diagnosed with clinical hypothyroidism. The remaining one was hyperthyroid on levothyroxin. Two women with subclinical hyperthyroidism in the first stage were normal in follow-up, without any treatment. In the first stage 2 men had subclinical hypothyroidism, and in follow-up, one was same, while the other was diagnosed with clinical hypothyroidism.

Normal range of TSH was 0.4-5.8 μu/mL in the Tehranian community. There was significant increase of the frequency of subclinical thyroid disorders in both genders and frequency of clinical hyperthyroidism and TPO-Ab positive in women. Compared to clinical thyroid disorders, the incidence of subclinical thyroid disorders, was more significant.

Postpartum thyroiditis is often a syndrome of transient thyroid dysfunction, but can develop to permanent hypothyroidism in some patients. The incidence of postpartum thyroiditis is variably reported, ranging from 1. 1% to 16. 7%, with an incidence ranging between 11% to 63% for permanent hypothyroidism. This study was conducted to assess the prevalence of permanent hypothyroidism after postpartum thyroiditis in Ahwaz.

All cases of postpartum thyroiditis referred to the endocrinology clinic between 1999 March and 2007 March were followed for 2 to 10 years. Levothyroxin was administered for 6 to 24 months after diagnosis, and then discontinued to evaluate the patients. Based on laboratory hormonal tests, patients were divided into 3 groups: 1) Normal thyroid function test, 2) Sub clinical hypothyroidism, and 3) Clinical hypothyroidism.

Fifty-eight women, were followed 6 months after discontining levothyroxin, twenty five (43. 1%) of group 1, 13 (22. 4%) of group 2, and 20 (34. 5%) in group 3. The average T4 level was significantly higher in group 1 compared to groups 2 and 3 (p =. 003). Permanent hypothyroidism was more frequent in patients who initially (during postpartum thyroiditis) had TSH levels >10 mg/dL. Occurrence of permanent hypothyroidism was less frequent in patients who were initially hyperthyroid. (p =. 006)

It is concluded that a high percentage of patients with postpartum thyroiditis proceed to permanent thyroid failure. The timely recognition of mild to severe cases of postpartum thyroiditis is important for the improvement of life for mothers and infants.

Obesity is an escalating public health problem. Adipose tissue synthesizes and secretes a variety of biological molecules, termed adipocytokines that may contribute to obesity-linked metabolic abnormalities, including cardiovascular diseases. We compared the effects of cow¢s milk, calcium fortified soy milk and calcium supplement on adipocytokines in premenopausal overweight and obese women.

In this clinical trial, 100 healthy overweight or obese premenopausal women were randomly allocated to one of the following dietary regimens for 8 weeks: 1) a control diet 2) a calcium- supplemented diet containing 800mg/d calcium carbonate 3) a high milk diet containing three servings of low fat milk or a 4) a soy milk diet containing three servings of calcium fortified soy milk (all of them providing a 500kcal/day deficit). At baseline and after 8 weeks, anthropometric indices and plasma leptin, adiponectin, TNFa, CRP, and IL-6 were measured.

Plasma CRP and leptin were significantly correlated with all anthropometric indices except for WHR, and plasma adiponectin had significant negative correlation with WHR at baseline. Although plasma leptin, CRP, and IL-6 decreased significantly in all groups (P<0. 01), except for CRP in the control group, there were no significant differences among four groups.

Results showed that a 500kcal/d deficit diet has beneficial effects on plasma adipocytokines, but calcium intake, either as calcium carbonate or as milk, causes no differences, and merits further research.

Obesity and physically inactive lifestyles are associated with an increased risk for developing insulin resistance. It has been confirmed that insulin resistance is a common feature in many inflammatory diseases and can be recognized with overproduced levels of markers such as IL-6, IL-18 & CRP. The aim of this study was to determine whether obesity or inactivity are stronger factors in the develop mental insulin resistance, considering insulin resistance markers such as IL-6, IL-18 and CRP.

Thirty-two healthy, male students participated in the present study, age 24. 8±2. 52 years, height 175. 47±6. 7, and weight 81. 64±20. 14). Weight and body fat were measured with the body composition set and levels of exercise was determined with the PA-Rscore questionnaire. All subjects based on body fat and levels of exercise were divided into 4 groups: Active obese(n=8), active, non-obese (n=8), inactive, obese (n=8) and inactive, non-obese (n=8). To determine fasting values of IL-6, IL-18, CRP, glucose and insulin blood samples were obtained at 8 a. m.

Obese subjects had higher resting levels of IL-6, IL18, CRP and insulin than lean subjects, with no significant difference between active lean and inactive lean subjects at resting levels of inflammatory markers. However there was a significant difference in the resting levels of IL-18 between active and inactive obese subjects (t=-2. 51 P=0. 031), and also a significant difference in resting levels of IL-6, IL-18,CRP, insulin and HOMA between inactive obese with active and inactive lean subjects, IL-18 having the strongest relationship with HOMA (r=0. 54 p=0. 001).

Results indicated that obesity is a stronger factor than inactivity for development of insulin resistance. On the other hand, activity has anti-inflammatory effects, and hence can decrease the effects of obesity, in the development of insulin resistance.

There is limited knowledge available on the metabolism of glucose in the brain, an insulin insensitive organ. Insulin receptors hybridize with insulin like growth factor receptor (IGF-I) to transduce the signals in different areas of the brain. In this article we aimed at investigating whether the expression of IGF-I receptor and IGF-I binding proteins (IGFBP1) is changed in the brain of the diabetic animal model.

To induce insulin resistance, adult wistar rats were fed with fructose in their drinking water (10%). The expression of IGF-I receptor and its binding protein were examined immunohistochemically.

Our findings demonstrated that the expression of IGF-I receptor and IGF-I binding protein were not changed in different areas of the brain in insulin resistant rats, compared to those in the control rats.

The unchanged expression levels of IGF-I receptor and its binding protein I not imply the lack of involvement of the IGF-I signal transduction pathway in the insulin resistant brain, further investigations are to clarify the issue.

The mass of adipose tissue expands during weight gain mostly because of an increase in fat cell diameter, which is one of the most important determinants of tissue metabolism. The aim of this study was to examine the effects of aging associated with weight gain on cell size and heterogeneity of adipocytes at different fat depots.

Adipose tissues were harvested from subcutaneous (SC), retroperitoneal (RP), perirenal (PR), proximal epididymal (PE) and distal epididymal (DE) regions of two groups of rats with a 30-day difference in age and 36% increase in body weight. Diameters of fat cells were measured using a microscope equipped with a calibrated micrometer. Cell size heterogeneity was deduced from coefficient of variation.

In both groups, no significant regional differences were observed in diameter of adipocytes in various fat depots. With the exception of the RP depot, the weight gain caused a significant increase in diameter of adipocytes in all other depots. The highest and the lowest increase were seen in PR and RP adipocyte diameter, respectively. The degree of heterogeneity of fat depots was not significantly altered by weight gain.

Aging associated with weight gain leads to fat cell hypertrophy in a depot specific manner, and cells at depots close to survival organs such as kidney and gonads are more affected than those of the other depots. The results of this study can enhance current knowledge on adipose tissue mass expansion and its related health complications such as cardiovascular diseases and diabetes.

The hypoglycemic effects of the Uritca Dioica (UD) extract, used for treatment of diabetes mellitus for many centuries, have been documented in several studies. The present study was designed to determine the possible mechanisms of hypoglycemic effects of UD on human muscle cells and RIN5F rat pancreatic b cells.

In the cell culture laboratory of the Drug Applied Research Center, pancreatic b cells and human muscle cells were prepared in multiple flasks containing culture media. Alcoholic extract of UD at concentrations of 50, 100 and 200 mg/mL were added to muscle cell flasks. The same concentrations of extract plus insulin were added to other muscle cell flasks. Glucose levels were measured in the flasks before and after 60, 120 and 180 minutes after adding of extract. Also the same concentrations of UD were added to flask containing RIN5F rat pancreatic b cells, and insulin and C-peptide level were measured at 0, 60, 120 and 180 minutes.

Mean glucose level in the muscle cell media with UD alone and UD plus insulin, at the concentrations and time intervals mentioned, did not change significantly. Insulin levels in pancreatic cells media, before and after applying of UD at different concentrations, and at different times was ≤0. 2 µg/ml. C-peptide (µg/ml) levels in these medias with a dose of 50 µg/ml of UD and at above mentioned times were 0. 31, 0. 33, 0. 86 and 0. 8 at concentration of 100 µg/mL they were 0. 7, 0. 2, 0. 4 and 0. 39, and at concentration of 200 µg/mL were 0. 32, 0. 33, 0. 93, 0. 77 respectively (Nonsignificant changes).

The results of the present study showed that alcoholic extract of UD was unable to increase insulin sensitivity in muscle cells and/or increase insulin and C-peptide secretion from RIN5F pancreatic b cells. It seems that hypoglycemic effects of UD were not mediated through the proposed mechanisms of this study.