Payam Salehi

Prevalence of metabolic syndrome in an urban population: Tehran Lipid and Glucose Study

The aim of the present investigation was to determine the prevalence of the metabolic syndrome among 103,68 of the adults (4,397 men and 5,971 women) aged 20 years and over, participating in the Tehran Lipid and Glucose Study. The metabolic syndrome was defined by the presence of three or more of the following components: abdominal obesity, hypertriglyceridemia, low HDL-C, high blood pressure, and high fasting glucose. The unadjusted prevalence of metabolic syndrome in the study population was 30.1% (CI 95%: 29.2-31.0) and age-standardized prevalence was 33.7% (CI 95%: 32.8-34.6). The prevalence increased with age in both sexes. The metabolic syndrome was more commonly seen in women than in men (42% vs. 24%, P<0.001). Low HDL-C was the most common metabolic abnormality in both sexes. Except for high FPG, all abnormalities were more common in women than in men (P<0.001). Most of those with metabolic syndrome had three components of the syndrome (58%), 33% had four, and 9% had five components. This report on the metabolic syndrome from Iran shows a high prevalence of this disorder. Efforts on promoting healthy diets, physical activity, and blood pressure control must be undertaken.

Cardiovascular risk factors in an Iranian urban population: Tehran Lipid and Glucose Study (Phase 1)

Summary.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 15005 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 1474 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.

Islet Transplantation for Brittle Type 1 Diabetes: The UIC Protocol

This prospective phase 1/2 trial investigated the safety and reproducibility of allogeneic islet transplantation (Tx) in type I diabetic (T1DM) patients and tested a strategy to achieve insulin‐independence with lower islet mass. Ten C‐peptide negative T1DM subjects with hypoglycemic unawareness received 1–3 intraportal allogeneic islet Tx and were followed for 15 months. Four subjects (Group 1) received the Edmonton immunosuppression regimen (daclizumab, sirolimus, tacrolimus). Six subjects (Group 2) received the University of Illinois protocol (etanercept, exenatide and the Edmonton regimen). All subjects became insulin‐ independent. Group 1 received a mean total number of islets (EIN) of 1460 080 ± 418 330 in 2 (n = 2) or 3 (n = 2) Tx, whereas Group 2 became insulin‐ independent after 1 Tx (537 495 ± 190 968 EIN, p = 0.028). All Group 1 subjects remained insulin free through the follow‐up. Two Group 2 subjects resumed insulin: one after immunosuppression reduction during an infectious complication, the other with exenatide intolerance. HbA1c reached normal range in both groups (6.5 ± 0.6 at baseline to 5.6 ± 0.5 after 2–3 Tx in Group 1 vs. 7.8 ± 1.1 to 5.8 ± 0.3 after 1 Tx in Group 2). HYPO scores markedly decreased in both groups. Combined treatment of etanercept and exenatide improves islet graft function and facilitates achievement of insulin‐independence with less islets.

5-Aminoimidazole-4-carboxamide riboside (AICAR) enhances GLUT2-dependent jejunal glucose transport: a possible role for AMPK

AMPK (AMP-activated protein kinase) is a key sensor of energy status within the cell. Activated by an increase in the AMP/ATP ratio, AMPK acts to limit cellular energy depletion by down-regulating selective ATP-dependent processes. The purpose of the present study was to determine the role of AMPK in regulating intestinal glucose transport. [3H]3-O-methyl glucose fluxes were measured in murine jejunum in the presence and absence of the AMPK activators AICAR (5-aminoimidazole-4-carboxamide riboside) and metformin and the p38 inhibitor, SB203580. To differentiate between a sodium-coupled (SGLT1) and diffusive (GLUT2) route of entry, fluxes were measured in the presence of the SGLT1 and GLUT2 inhibitors phloridzin and phloretin. Glucose transporter mRNA levels were measured by reverse transcriptase-PCR, and localization by Western blotting. Surface-expressed GLUT2 was assessed by luminal biotinylation. Activation of p38 mitogen-activated protein kinase was analysed by Western blotting. We found that treatment of jejunal tissue with AICAR resulted in enhanced net glucose uptake and was associated with phosphorylation of p38 mitogen-activated protein kinase. Inhibition of p38 abrogated the stimulation of AICAR-stimulated glucose uptake. Phloretin abolished the AICAR-mediated increase in glucose flux, whereas phloridzin had no effect, suggesting the involvement of GLUT2. In addition, AICAR decreased total protein levels of SGLT1, concurrently increasing levels of GLUT2 in the brush-border membrane. The anti-diabetic drug metformin, a known activator of AMPK, also induced the localization of GLUT2 to the luminal surface. We conclude that the activation of AMPK results in an up-regulation of non-energy requiring glucose uptake by GLUT2 and a concurrent down-regulation of sodium-dependent glucose transport.

Serum lipid levels in an Iranian adults population: Tehran lipid and glucose study

Data from 6246 participants aged 20–64 years (2339 males and 3907 females) in the cross-sectional phase of Tehran Lipid and Glucose Study (February 1999–May 2000) were used to determine distribution of serum lipid levels after 12–14 hour overnight fast. Mean total cholesterol (TC) concentration was 210 mg/dl. TC was significantly greater in females than males, 213 and 206 mg/dl, respectively (p < 0.0001). Thirty-one percent of population had TC values between 200 and 239 and 24% had values of 240 mg/dl or greater. Mean low-density lipoprotein cholesterol (LDL-C) was 129 and 135 mg/dl in males and females, respectively (p < 0.0001). Twenty-seven percent had LDL-C values between 130 and 159 and 23% had values 160 mg/dl or greater. The mean triglycerides (TGs) values were 190 and 162 mg/dl for males and females, respectively (p < 0.0001). The mean high-density lipoprotein cholesterol (HDL-C) was 39 in males and 45 mg/dl in females (p < 0.0001). The results showed higher levels of TC, LDL-C and TGs and slightly lower HDL-C in Tehranian adults than other studies in the industrialized countries.

Islet isolation and transplantation outcomes of pancreas preserved with University of Wisconsin solution versus two-layer method using preoxygenated perfluorocarbon

Background. Previous small clinical trials indicate that the two-layer method (TLM) for pancreas preservation improves islet isolation outcome. However, the effect of TLM has not been evaluated in large-scale study. In addition, a direct benefit of TLM on islet transplantation outcome has not been addressed in the setting of any randomized controlled trials. Methods. Between April 2003 and October 2005, human pancreata from brain-dead donors were preserved by TLM using preoxygenated perfluorocarbon (n=75) or in University of Wisconsin (UW) solution (n=91) prior to islet isolation. Islet isolation and transplantation outcomes were compared between the two groups. Results. We did not find any significant differences in adenosine triphosphate content in pancreatic tissue after preservation, pre and postpurification islet yields, in vitro insulin secretory function, or utilization ratio of transplantation between the two groups. Transplanted mass and functional viability of islet isolated from TLM-preserved pancreas were similar to those from UW-preserved pancreas. Patients receiving the TLM-islet or the UW-islet showed a marked decrease in insulin requirement after transplantation. However, no significant difference was observed in a decrease in insulin requirement between patients receiving the TLM-islet and the UW-islet. Conclusions. No beneficial effect of TLM on islet isolation and transplantation outcomes was observed. Our findings bring into question the true merit of routine use of TLM prior to islet isolation.

Encapsulation of Human Islets in Novel Inhomogeneous Alginate-Ca2+/Ba2+ Microbeads : In Vitro and In Vivo Function

Microencapsulation may allow for immunosuppression-free islet transplantation. Herein we investigated whether human islets can be shipped safely to a remote encapsulation core facility and maintain in vitro and in vivo functionality. In non-encapsulated islets before and encapsulated islets after shipment, viability was 88.3±2.5 and 87.5±2.7% (n=6, p=0.30). Stimulation index after static glucose incubation was 5.4±0.5 and 6.3±0.4 (n=6, p=0.18), respectively. After intraperitoneal transplantation, long-term normoglycemia was consistently achieved with 3,000, 5,000, and 10,000 IEQ encapsulated human islets. When transplanting 1,000 IEQ, mice returned to hyperglycemia after 30-55 (n=4/7) and 160 days (n=3/7). Transplanted mice showed human oral glucose tolerance with lower glucose levels than non-diabetic control mice. Capsules retrieved after transplantation were intact, with only minimal overgrowth. This study shows that human islets maintained the viability and in vitro function after encapsulation and the inhomogeneous alginate-Ca2+/Ba2+ microbeads allow for long-term in vivo human islet graft function, despite long-distance shipment.

Cardiovascular Risk Factors in the Elderly: The Tehran Lipid and Glucose Study:

Background Coronary artery disease is becoming more prevalent in developing countries, particularly in urban areas. Because the proportion of elderly individuals in the population is on the rise, this study was conducted to determine the prevalence of cardiovascular risk factors among the Tehran urban elderly population. Design and methods Among 15005 urban individuals of 3 years old and over who had been chosen in a cross-sectional phase of a longitudinal study in Tehran, there were 1799 people aged 60 years and over. The prevalence and distribution of high blood pressure, cigarette smoking, dyslipoproteinemia, diabetes mellitus and obesity were determined in this population. Dietary intake was assessed in a subsidiary of 54 people by means of two 24 h dietary recalls. Results The percentage of women with two or more cardiovascular disease risk factors was significantly greater than in men (74% compared with 53%, P < 0.001). One fourth of men and 55% of women had high serum cholesterol levels (≥240 mg/dl). The prevalence of diabetes mellitus and impaired glucose tolerance was 24% and 21% in men and 29% and 20% in women, respectively. The prevalence of obesity (body mass index ≥30kg/m2) was 15% for men and 36% for women. Fifty-five per cent of men and 94% of women had high waist-to-hip ratios (>0.95 in men and >0.8 in women). The mean percentage values of energy intake derived from carbohydrate, protein and fat were 60.5 ± 8.0, 11.5 ± 2.0 and 27.8 ± 8.9, respectively. Conclusions The prevalence of cardiovascular risk factors among the Tehran urban elderly population is high. Some efforts should be made to reverse the recent trend towards increasing age-related mortality and morbidity rates of coronary heart disease.

Ameliorating Injury During Preservation and Isolation of Human Islets Using the Two-Layer Method With Perfluorocarbon and UW Solution

This study assessed the effects of a two-layer method (TLM), using perfluorocarbon and UW solution, on the quality of human pancreata following storage and islet yield/function after isolation. In part A, TLM was applied immediately after procurement and the energetic profile was compared to a group treated with UW solution only (control) throughout 24-h storage. In part B, cadaveric human pancreata were procured and subjected to a TLM after cold storage in UW solution (TLM group) or UW solution (control group). Energetics, lipid peroxidation, and islet recovery/function were assessed after preservation at 4°C. In part A, after 9-h storage, the energetic profile (ATP, ATP/ADP, energy charge) for the TLM group was superior to controls. In part B, TLM treatment resulted in consistently greater ATP, ATP/ADP, and energy charge values than with storage in UW solution alone (p < 0.05). UW treatment resulted in 40% greater peroxidative damage than in the TLM group (p < 0.05). Islet recovery and functional viability were 30–40% higher following TLM treatment (p < 0.05). These data support the hypothesis that islet viability and yields can be significantly improved using a brief period of TLM treatment following conventional UW storage; reduced energetic and oxidative stress are implicated as potential mechanisms.

Improved outcomes in islet isolation and transplantation by the use of a novel hemoglobin-based O2 carrier.

During isolation, islets are exposed to warm ischemia. In this study, intraductal administration of oxygenated polymerized, stroma‐free hemoglobin‐pyridoxalated (Poly SFH‐P) was performed to improve O2 delivery. Rat pancreata subjected to 30‐min warm ischemia were perfused intraductally with collagenase in oxygenated Poly SFH‐P/RPMI or RPMI (control). PO2 was increased by Poly SFH‐P (381.7 ± 35.3 mmHg vs. 202.3 ± 28.2, p = 0.01) and pH maintained within physiological range (7.4–7.2 vs. 7.1–6.6, p = 0.009). Islet viability (77%± 4.6 vs. 63%± 4.7, p = 0.04) was improved and apoptosis lower with Poly SFH‐P (caspase‐3: 34,714 ± 2167 vs. 45,985 ± 1382, respectively, p = 0.01). Poly SFH‐P improved islet responsiveness to glucose as determined by increased intracellular Ca2+ levels and improved insulin secretion (SI 5.4 ± 0.1 vs. 3.1 ± 0.2, p = 0.03). Mitochondrial integrity was improved in Poly SFH‐P‐treated islets, which showed higher percentage change in membrane potential after glucose stimulation (14.7%± 1.8 vs. 9.8 ± 1.4, respectively, p < 0.05). O2 delivery by Poly SFH‐P did not increase oxidative stress (GSH 7.1 ± 2.9 nm/mg protein for Poly SFH‐P vs. 6.8 ± 2.4 control, p = 0.9) or oxidative injury (MDA 1.8 ± 0.9 nmol/mg protein vs. 6.2 ± 2.4, p = 0.19). Time to reach normoglycemia in transplanted diabetic nude mice was shorter (1.8 ± 0.4 vs. 7 ± 2.5 days, p = 0.02), and glucose tolerance improved in the Poly SFH‐P group (AUC 8106 ± 590 vs. 10,863 ± 946, p = 0.03). Oxygenated Poly SFH‐P improves islet isolation and transplantation outcomes by preserving mitochondrial integrity.