Endocrinology and Metabolism Research Institute from inception to maturity: an overview of 25-year activity.

Endocrinology and Metabolism Research Institute (EMRI) was founded in 1993. EMRI progressed step by step from inception and reached to its maturation during the past 25 years. EMRI has expanded and progressed in different aspects including human resources and infrastructures (laboratories and new technologies) and has obtained the first rank in the country in endocrinology research. It has also collaborated with regional and international organizations such as World Health Organization (WHO), International Osteoporosis Foundation (IOF), and American Association of Clinical Endocrinologists (AACE). This article provides an overview of EMRI activities during a quarter of a century.

Unusual Ectopic Parathyroid Adenoma: A Case Report.

An ectopically placed parathyroid in the mediastinum is a rare cause of persistent or recurrent primary hyperparathyroidism. They are rarely in a huge size. We report a case of a 70-year-old man with a history of total parathyroidectomy and thymectomy presented with a lack of appetite, nausea, and generalized bone pain, polydipsia and a calcium level of 14.4 mg/dl. 99mTc-sestamibi scintigraphy with single-photon emission computerized tomography (SPECT) showed a focal zone of radiotracer accumulation in the midline of anterior chest wall (xiphoid level). The mass excised from our patient surgically was 75 grams. This weight and location of the tumor is a very rare finding in parathyroid adenomas.

Elevated serum levels of pregnancy-associated plasma protein-A in type 2 diabetics compared to healthy controls: associations with subclinical atherosclerosis parameters.

Type 2 diabetes mellitus is associated with increased inflammation and accelerated atherosclerosis. The association of the pro-inflammatory and potentially pro-atherosclerotic molecule, pregnancy associated plasma protein-A (PAPP-A) with diabetes and vascular diseases remains to be further established. A total of 107 patients with type 2 diabetes and 101 healthy controls participated in this study. Serum levels of PAPP-A was measured by Enzyme-linked Immunosorbent Assay (ELISA). We also evaluated the lipid profile, aortic augmentation index, coronary calcium score, ankle brachial index, flow mediated dilation, and carotid intima media thickness. Serum level of PAPP-A was significantly higher in patients with diabetes compared to controls (P<0.001). In the multivariable regression analysis, PAPP-A was positively correlated with diabetes (P<0.001), aortic augmentation index (P=0.021) and was negatively associated with coronary calcification (P=0.050). In conclusion, serum levels of PAPP-A were significantly higher in diabetics compared to healthy controls and correlated with aortic augmentation index and coronary calcification. Our study results suggest that PAPP-A can be a marker of subclinical atherosclerosis in patients with diabetes.

Who are diabetic foot patients? A descriptive study on 873 patients.

BACKGROUND: Diabetic foot ulcer (DFU) as the leading cause of lower limb amputation is one of the most important complications of diabetes mellitus (DM). Patient and physician's education plays a significant role in DFU prevention. While effective treatment and formulation of prevention guidelines for DFU require a thorough understanding of characteristics of DFU patients and their ulcers, there are reports that not only patients' but also physicians' information about these characteristics is inadequate. So we conducted this study to investigate these characteristics. METHODS: Necessary data was collected from medical archives of DFU patients admitted between 2002 and 2008 in two university hospitals. RESULTS: 873 patients were included. Mean age was 59.3 ± 11.2 years and most of the patients developed DFU in 5th and 6th decades of their life. 58.1% were men. 28.8% had family history of DM. Mean duration of DM was 172.2 months. Mean duration of DFU was 79.8 days. Only 14.4% of the patients had Hemoglobin A1C < 7%. 69.6% of the patients had history of previous hospitalization due to DM complications. The most prevalent co-morbidities were renal, cardiovascular and ophthalmic ones. Most patients had "ischemic DFU" and DFU in their "right" limb. The most prevalent location of DFU was patients' toes, with most of them being in the big toe. 28.2% of the patients underwent lower-limb amputations. The amputation rate in the hospital where the "multidisciplinary approach" has been used was lower (23.7% vs. 30.1%). CONCLUSIONS: Number of patients with DFU is increasing. DFU is most likely to develop in middle-aged diabetic patients with a long duration of DM and poor blood sugar control who have other co-morbidities of DM. Male patients are at more risk. Recurrence of DFU is a major point of concern which underscores the importance of patient education to prevent secondary ulcers. As a result, educating medical and nursing personnel, applying screening and prevention guidelines, and allocating more resources are of great importance regarding treatment of DFU patients. Application of the "multidisciplinary approach" can reduce the rate of amputations. Primary care physicians might be furnished with the information presented in the present study.

Investigation The Role of Gender on The HLA-DRB1 and -DQB1 Association with Type 1 Diabetes Mellitus in Iranian Patients.

OBJECTIVE: Type 1 diabetes mellitus (T1D) is an autoimmune and multifactorial disorder. Subsequent analysis on human leukocyte antigen ( HLA) region shows that HLA-DRB1 and -DQB1 genes have the strongest association with T1D. In this study, for the first time, we investigated the influence of gender on the HLA-DRB1 and -DQB1 association with type 1 diabetes mellitus in Iranian patients in order to determine gender dependent HLA heterogeneity in Iranian T1D patients. MATERIALS AND METHODS: In this case control study, the HLA-DRB1 and -DQB1 typing were performed on 105 Iranian T1D patients and 100 healthy controls. The data were evaluated by using Fisher exact test. RESULTS: Our results indicate that DRB1*04:01, DQB1*03:02 alleles and DRB1*04:01- DQB1*03:02 haplotype were significantly more frequent in male T1D patients than females. Also, DRB1*03:01, DRB1*15:01, DQB1*06:01 alleles, DQB1*03:01/05:01 genotype, DRB1*03:01-DQB1*02:01 and DRB1*15:01-DQB1*06:01 haplotypes were significantly higher in female T1D group than males. Furthermore, our results showed that DRB1*04:01 and DQB1*03:02 alleles were significantly more frequent in male T1D patients 1-5 years old at onset than females with similar condition. The DRB1*03:01 allele and DRB1*03:01- DQB1*02:01 haplotype were significantly higher in female T1D patients 6-10 years old at onset than males with similar condition. The DRB1*15:01 allele and DRB1*15:01-DQB1*06:01 haplotype were significantly more frequent in female T1D patients 16-20 years old at onset than males with similar condition. CONCLUSION: Our findings suggest that gender has a significant influence on the distribution of HLA-DR and -DQ alleles, genotypes and haplotypes. Also, distribution of the HLA-DRB1 and -DQB1 alleles, genotypes and haplotypes vary based on the gender of T1D patients in different age at onset.

The importance of hypoglycemia in diabetic patients.

Hypoglycemia is one of the most important complications of diabetes treatment. The risk of severe hypoglycemia is higher in elderly patients, those having comorbidities such as vascular disease or renal failure, pregnant women and in children with type 1diabetes. Moreover, in type 2 diabetes, progressive insulin deficiency, longer duration of diabetes, and tight glycemic control increase the risk of hypoglycemia as much as type 1 diabetes.Episodes hypoglycemia may lead to impairment of counter-regulatory system, with the potential of development of hypoglycemia unawareness. So, hypoglycemia may increase the vascular events even death in addition to other possible detrimental effects. Glycemic control should be individualized based on patient characteristics with some degree of safety. Recognition of hypoglycemia risk factors, blood glucose monitoring, selection of appropriate regimens and educational programs for healthcare professionals and patients with diabetes are the major issues to maintain good glycemic control, minimize the risk of hypoglycemia, and prevent long- term complications.

Association study of the -866G/A UCP2 gene promoter polymorphism with type 2 diabetes and obesity in a Tehran population: a case control study.

BACKGROUND: A functional polymorphism in the uncoupling protein 2 (UCP2) gene promoter has been associated with obesity and type 2 diabetes (T2D) in some populations. The impact of UCP2 polymorphisms on diabetes and obesity is still under debate. Contradictory results have been reported in different populations world-wide. To clarify the contribution of the UCP2 gene -866 G/A polymorphism in the Iranian population, we studied its association with obesity and T2D. METHODS: A total of 225 unrelated subjects were studied: 75 T2D patients without obesity, 75 obese patients without diabetes and 75 control subjects. The UCP2 -866 G/A polymorphism was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: In the normal Iranian population, GG polymorphism was significantly associated with an increased HDL-C level (P=0.027). G/A polymorphism was not associated with obesity and T2D in our study population, but the odds ratio (OR) between GG and G/A polymorphism was 0.61 with a confidence interval (CI) range of 0.34 - 1.08 in obese patients. Subjects with AA genotypes in all of the studied groups showed a lower body mass index (BMI) than subjects with the GG genotype. CONCLUSION: Although the data in our study population is not statistically significant, the A allele in the UCP2 gene promoter seems to be protective against obesity. This may suggest the possibility of UCP2 as a target molecule for studies on the etiology and treatment of obesity.

Effects of natural honey consumption in diabetic patients: an 8-week randomized clinical trial.

OBJECTIVES: We investigated the effect of natural honey on body weight and some blood biochemical indices of diabetic subjects. METHODS: Forty-eight diabetic type 2 patients were randomly assigned into two groups: the honey group received oral natural honey for 8 weeks, and the control group did not take honey. Before the onset of the study (week 0) and after 8 weeks, weight measurements were taken and fasting blood samples were drawn. RESULTS: After adjustment for the baseline values, there were no significant differences in the fasting blood sugars between the two groups. Body weight, total cholesterol, low-density lipoprotein-cholesterol and triglyceride decreased (P = 0.000), and high-density lipoprotein-cholesterol increased significantly (P < 0.01) in honey group. The levels of hemoglobin A(1C) increased significantly in this group (P < 0.01). CONCLUSION: The results of this study demonstrate that 8-week consumption of honey can provide beneficial effects on body weight and blood lipids of diabetic patients. However, since an increase in the hemoglobin A(1C) levels was observed, cautious consumption of this food by diabetic patients is recommended.

The common -866G/A polymorphism of the UCP2 gene in healthy Iranians compared with world populations.

Uncoupling protein 2 (UCP2) is a member of the mitochondrial transporter superfamily. It is proposed as a candidate gene for obesity. A common G/A polymorphism in the promoter region of this gene is associated with enhanced adipose tissue mRNA expression in vivo. Using a PCR-RFLP method, we genotyped the UCP2 -866G/A polymorphism in 75 unrelated nonobese nondiabetic Iranians. The frequencies of the UCP2 -866G/A genotypes in 75 Iranian normal subjects were 7 (9.4%) for AA, 41 (54.6%) for GA, and 27 (36%) for GG. Significantly higher HDL cholesterol was detected in people with the GG genotype (p = 0.02) compared to individuals with the GA and AA genotypes. The frequency distribution results were compared with data from Japanese, Italians, Germans, Austrians, and Danes. Our allele frequencies were significantly different from the Japanese data from two different reports (P < 0.025) but not from the others. The Japanese data showed a higher frequency of the AA genotype, which is associated with a low prevalence of obesity, than the Caucasian individuals' data did. In conclusion, a single nucleotide polymorphism in the promoter region of the UCP2 gene has a significant association with HDL cholesterol level in Iranian nonobese nondiabetic subjects. Also, our allele-frequency distribution for this single nucleotide polymorphism is closer to European Caucasians than to Japanese in nonobese nondiabetic individuals.

Are biochemical values predictive of adenoma's weight in primary hyperparathyroidism?

BACKGROUND: Preoperative laboratory findings may carry some predictive value about the size of the abnormal parathyroid tissue that needs to be removed in primary hyperparathyroidism. METHODS: In a retrospective study from 1988 to 2003, records of 71 patients with parathyroid adenoma were reviewed. The correlation between preoperative serum calcium, phosphate and parathyroid hormone (PTH) with adenoma's weight was analysed separately. RESULTS: There was a significant correlation between preoperative serum PTH and calcium with adenoma's weight (P < 0.001 and P = 0.03, respectively). The correlation between preoperative serum phosphate and adenoma's weight was not significant (P = 0.1). CONCLUSION: Preoperative PTH level cannot be used as a definite guide to the parathyroid adenoma's weight. Large parathyroid adenomas seem to secrete less PTH per unit weight than small adenomas. Calcium and phosphate do not seem to be of much value in predicting adenoma's weight in primary hyperparathyroidism.

The status of biochemical parameters in varying degrees of vitamin D deficiency.

Vitamin D (Vit D) is an essential element for the regulation of serum calcium, phosphate, and alkaline phosphatase (Alk Ph). Because the Vit D serum level is not usually measured directly, Vit D deficiency is diagnosed indirectly by changes in serum calcium, phosphate, and Alk Ph leves. The current study assessed the status of these biochemical parameters in subjects with different degrees of Vit D deficiency. We selected 1,210 subjects, between 20 and 69 years old, randomly from the Tehran population. Subjects with diseases or medications that modified bone metabolism were excluded from the study. Serum 25(OH) D, calcium, phosphate, Alk Ph, and parathyroid hormone (PTH) levels were measured and the status of these biochemical parameters was compared in subjects with different degrees of Vit D deficiency. Vit D deficiency was diagnosed in 79.6% of the subjects. Different degrees of Vit D deficiency were classified as follows: group 1, severe; group 2, moderate; and group 3, mild. Serum PTH levels in the Vit D-deficient groups were significantly higher than that in group 4 (normal Vit D). Serum calcium and phosphate levels in groups 1 and 2 were significantly lower than those in groups 3 and 4. No significant difference was seen in serum Alk Ph in the groups with different degrees of Vit D deficiency. The sensivity for at least one biochemical variable (calcium, phosphorus, or Alk Ph) for the detection of severe, moderate, and mild Vit D deficiency was 24.2%, 13.8%, and 6%, respectively. When the serum 25(OH) D level was reduced to less than 25 nmol/l (groups 1 and 2), the effects of Vit D deficiency on calcium and phosphate levels were obvious. Therefore, the usual biochemical parameters (calcium, phosphate, Alk Ph) alone do not have sufficient sensitivity to detect mild deficiency of Vit D.

Potential risk factors for diabetic neuropathy: a case control study.

BACKGROUND: Diabetes mellitus type II afflicts at least 2 million people in Iran. Neuropathy is one of the most common complications of diabetes and lowers the patient's quality of life. Since neuropathy often leads to ulceration and amputation, we have tried to elucidate the factors that can affect its progression. METHODS: In this case-control study, 110 diabetic patients were selected from the Shariati Hospital diabetes clinic. Michigan Neuropathic Diabetic Scoring (MNDS) was used to differentiate cases from controls. The diagnosis of neuropathy was confirmed by nerve conduction studies (nerve conduction velocity and electromyography). The multiple factors compared between the two groups included consumption of angiotensin converting enzyme inhibitors (ACEI), blood pressure, serum lipid level, sex, smoking, method of diabetes control and its quality. RESULTS: Statistically significant relationships were found between neuropathy and age, gender, quality of diabetes control and duration of disease (P values in the order: 0.04, 0.04, < 0.001 and 0.005). No correlation was found with any atherosclerosis risk factor (high BP, hyperlipidemia, cigarette smoking). CONCLUSION: In this study, hyperglycemia was the only modifiable risk factor for diabetic neuropathy. Glycemic control reduces the incidence of neuropathy, slows its progression and improves the diabetic patient's quality of life. More attention must be paid to elderly male diabetic patients with poor diabetes control with regard to regular foot examinations and more practical education.

Normative data of bone Mineral Density in healthy population of Tehran, Iran: a cross sectional study.

BACKGROUND: Osteoporosis is a major problem and is a hidden epidemic disease in the world. Early diagnosis by measurement of Bone Mineral Density (BMD) and treatment can prevent and reduce disease complications, especially fractures. As there is no comprehensive study in Iran, this study designed to assess BMD discrepancy in 20-69 yr Tehran population as well as prevalence of osteoporosis and osteopenia. METHODS: 553 people (34% men, 66%women) from 50 Blocks in Tehran randomly selected. The assessment of BMD in spine and femur region performed through DXA method. All subjects clinically examined and their BMIs determined. RESULTS: The average spinal BMD score in men were more than in women. The peak bone mass of spine bone both in men and women occurred during 20-29 yr and reduction began from the age of 40. At the age of 60 to 69, loose of bone density was 19.6% in lumbar spine and 18.5% in femur of women and also 7.9% in lumbar spine and 14.6% in femur of men. Prevalence of osteoporosis in this age group in lumbar spine and femur was 32.4% and 5.9% in women and 9.4% and 3.1% in men respectively. CONCLUSION: In all age groups, peak bone mass was lower than European or American population, whereas the rate of bone loss was as much as the some population and actually this process justifies the prevalence of osteoporosis and osteopenia in Tehran population.

Insulinoma in Iran: a 20-year review.

BACKGROUND: The time between onset of symptoms of insulinoma to diagnosis ranges from 10 days to more than 20 years. To help physicians make an earlier diagnosis, we defined the clinical, imaging and paraclinical characteristics of insulinoma in cases from seven referral hospitals in Iran over two decades. METHODS: The medical records of 68 cases with biochemical or histological evidences of insulinoma were reviewed. RESULTS: More males were affected (53%). The mean age at diagnosis was 39 +/- 15.3 years. The mean duration of symptoms was 39.9 +/- 59.3 months. Eighty-four percent of patients had been initially misdiagnosed as cereberovascular accident (CVA), epilepsy, conversion disorder, and others). Neuroadrenergic symptoms were observed in 89.6% and and neuroglycopenic symptoms in 97% of patients. Mean diameter of tumours was 2.9 cm (range, 1 cm to 8.5 cm). Of 52 pathologically confirmed cases of insulinoma, 43 tumours (87.8%) were single and 49 (94.2%) were benign. Fifty-five patients had undergone surgery, with a successful outcome in 44 (80%). CONCLUSION: The high incidence of neuroglycopenic symptoms suggest the clinical impression of insulinoma when patients present with a suggestive clinical syndrome. The clinical impression is essential to decrease the frequent delay in the diagnosis of insulinoma.

Vitamin D deficiency and causative factors in the population of Tehran.

BACKGROUND: There are multiple studies in different countries regarding the prevalence of vitamin D deficiency. These studies showed high prevalence of vitamin D deficiency in Asian countries. This study tries to elucidate the prevalence of vitamin D deficiency and its influencing factors in population of Tehran. METHODS: 1210 subjects 20-64 years old were randomly selected. 25 (OH) D serum levels were measured. Duration of exposure to sunlight, the type of clothing and level of calcium intake and BMI were quantified based on a questionnaire. RESULTS: A high percentage of vitamin D deficiency was defined in the study population. Prevalence of severe, moderate and mild Vitamin D deficiency was 9.5%, 57.6% and 14.2% respectively. Vitamin D serum levels had no significant statistical relation with the duration of exposure to sunlight, kind of clothing and BMI. Calcium intake in the normal vitamin D group was significantly higher than the other groups (714.67 +/- 330.8 mg/day vs 503.39 +/- 303.1, 577.93 +/- 304.9,595.84 +/- 313.6). Vitamin D serum levels in young and middle aged females were significantly lower than the older group. CONCLUSIONS: Vitamin D deficiency has a high prevalence in Tehran. In order to avoid complications of vitamin D deficiency, supplemental dietary intake seems essential.

Treatment of hyperfunctioning thyroid nodules by percutaneous ethanol injection.

BACKGROUND: Autonomous thyroid nodules can be treated by a variety of methods. We assessed the efficacy of percutaneous ethanol injection in treating autonomous thyroid nodules. METHODS: 35 patients diagnosed by technetium-99 scanning with hyperfunctioning nodules and suppressed sensitive TSH (sTSH) were given sterile ethanol injections under ultrasound guidance. 29 patients had clinical and biochemical hyperthyroidism. The other 6 had sub-clinical hyperthyroidism with suppressed sTSH levels (<0.24 &mgr;IU/ml) and normal thyroid hormone levels. Ethanol injections were performed once every 1-4 weeks. Ethanol injections were stopped when serum T3, T4 and sTSH levels had returned to normal, or else injections could no longer be performed because significant side effects. Patients were followed up at 3, 6 and, in 15 patients, 24 months after the last injection. RESULTS: Average pre-treatment nodule volume [18.2 PlusMinus; 12.7 ml] decreased to 5.7 PlusMinus; 4.6 ml at 6 months follow-up [P < 0.001]. All patients had normal thyroid hormone levels at 3 and 6 months follow-up [P < 0.001 relative to baseline]. sTSH levels increased from 0.09 PlusMinus; 0.02 &mgr;IU/ml to 0.65 PlusMinus; 0.8 &mgr;IU/ml at the end of therapy [P < 0.05]. Only 3 patients had persistent sTSH suppression at 6 months post-therapy. T4 and sTSH did not change significantly between 6 months and 2 years [P > 0.05]. Ethanol injections were well tolerated by the patients, with only 2 cases of transient dysphonia. CONCLUSION: Our findings indicate that ethanol injection is an alternative to surgery or radioactive iodine in the treatment of autonomous thyroid nodules.