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POSTER PRESENTATIONS 191 I pnysiolans' Oplhions on Hip fracture preventlon Strategies in Long-term Care ANNA M. SAWKA- ' PARMINDER RAINA', SHARON STRAIJS,' NOFISAT ISMAIl-A,' LEHANA THABANE: JONATHAN O. ADACHI , AMIRAM GAFNI 1 ALEXANDRA PAPAIOANNOU i 'university of Toronto, Toronto, ON; 'McMaster University. Hamllton , ON Design. Senlng . and Par1lclpants: We oonducted a cross, seclional study, collecting data using-a self-administered . wNltel'l quesUonnai re . The su/Vey was mailed on 2008 to 246 Canadian Geriatrlolans In active practice , as well as Ontario Family Physicians belonging to tI1e Ontario Long - term Care Assocfation. We examI ned physicians' opinions on the utflfty 01 various hip fracture prevention strategles In tong-term care. Results: Tne results ftom the Rrst65 respondents ere presentee herein but Updated data will be presented at tI1e conference. About two-thirds of respondents were family phySICi ans (44165) and the rest wele gertatriCi ans. Most respondents (61/65) performed Clinical war1<. related to the care of elderly residents 01 long-term faCilities. Respondents strongly bel ieved that el f residents 01 long-term care facilities should be targeted for hlp fracture pneventlon strategies (mean 6.1 Bout 017 on a Likert scale). The majority of respondents very strongly recommended the use of the followi ng strategies In long-term care; calcium, vitamtn 0, oral amfno-blsphasphanates (alandronate or risedronate), physical therapy, and environmental modificatfon (such as hand ralls). The majority did not recommend the use of t/1e follOWing In long- term care; post-menopausal hannone testosterone, or teriperallde, Most respondents either did not recommend or recommended limited use (if other treatments contraindicated or not tolerated) of the fol loWing: etldronate, ihtravenaus blsphasphanates, and ralaxi(ene . Support was ml)(ed for hip protectors, B-vltamlns and , folate . Conclusions: Hlp fracture prevention in long-term care has been identified as an priority by Canadian physiCians , Calcl\Jm. Vitamin D, potent oral bisphosphanales and phYSical measures haVe been reoormneflded for LIse in long-term care , 193 I Study of Adiponectin Level and Adiponectin Gene Mutation in Type 2 Diabetic Patients with Coronary Artery Disease Yehia M. Ghanem"", Mohamed A. Sobhy""*, Mohamed M. Elsawy***, Mohamed A. Abd Elmohsen* Departments of Diabetes*, Cardiology**, and Clinical Pathology***, Faculty of Medicine, University of Alexandria, Alexandria, Egypt. Abstract Adiponectin occupies a unique place among adipokines, being the only one having anti-atherogenic, insulin sensitizing, anti-inflammatory, hepato- protective, anti-angiogenic and anti-tumour functions. Several polymorph isms have been identified in the adiponectin gene were found to be associated with low adiponectin levels, features of insulin resistance and CAD. The aim of the present study was to determine the adiponectin level and the frequency of 1164T mutation in the adiponectin gene in type 2 diabetic patients with CAD. The present study included 150 male subjects. They were classified as: Group (1): 100 patients with type 2 DM and CAD. Group (2): 50 control persons with no OM or CAD. All selected individuals were subjected to the following: Full history taking, complete clinical examination laboratory investigation: Fasting serum insulin level and HOMA-IR, Lipid profile, Kidney functions, Serum adiponectin level, DNA extraction & genotyping for detection of polymorphism of 1164T in adiponectin gene. Resting ECG, and Cardiac catheterization and coronary angiography. The results of the present study showed that Group 1 had statistically significant higher mean values of waist circumference, BMI, SB/P, FPG, 2HPPPG. fasting insulin. HbA1c. HOMA·IR. TC. TG. LDL·C. BUN and creatinine but had lower mean value of HDL-C and serum adiponectin, also the frequency of adiponectin gene polymorphism was statistically significantly higher in group 1 than in group 2. Also, there were statistically significant higher mean values between subjects carrying the 1164T mutation than those without the mutation as regard FPG, fasting insulin, HOMA-IR, TC, LDL-C and number of diseased coronary arteries. There was a lower mean va lue of adiponectin level in subjects carrying the 1164T mutation than those without the mutation but with no statistical significance. there was no statistical significant difference between presentation of CAD with either adiponectin level or presence of polymorphism. Also in our study, smokers had a significant lower mean va lue of adiponectin level with no significance difference with incidence of polymorphism. Adiponectin level showed a significant negative correlation with SB/P, DB/P, FPG, 2HPPG, HbA1c, fasting insulin, HOMA-IR, TC, LDL-C, number of diseased coronary arteries and severity of coronary artery stenosis according to gensini score and showed a significant positive correlation with HDL-C. 192 I MONTREAL 2008 ABSTRACTS I 351 Loss of the Circadian Rhythm Gene Magel2 Leads to Metabolic Changes and Reduced Ferlility in Mice. REBECCA E. MERCER*, and RACHEL WEYRICK, Department of Medical Genetics, University of Alberta, Edmonlon , AB. We have identified the Prader-Willi Syndrome (PWS) candidate gene MAGEL2 as a circadian output gene rhythmically expressed in the suprachiasmatic nucleus (SCN) of the hypothalamus in mice. People with PWS have profound metabolic disturbances, beginning with a period of poor growth as infants, followed by childhood- onset hyperphagia, which in the absence of strict intervention leads to morbid obesity, insulin resistance, type 2 diabetes, and cardiovascular disease. Those with PWS also manifest reproducti ve difficulties, including delayed and incomplete puberty, sporadic menses, and infertility. The combined features of PWS directly link a genetic defect to primary hypothalamic dysfunction. The proposed roles of circadian rhythm in the maintenance of energy balance and reproductive fitness prompted us to examine these functions in mice lacking Magel2, referred to as Magei2-null. The mice recapitulate several growth phenotypes of PWS, including an early followed by increased weight gain and adiposity following weaning. Magef2-null mice also display abnormal feeding patterns, including reduced food intake, a shift in the timing of food consumption, and an aversion to novel food sources. Reproductive alterations, including a delay in puberty, delay in time-to-mating, early decline in fertility, abnormal estrous cycles, and reduced testosterone levels are consistently observed in Magel2-null mice. These changes are similar to those observed in other circadian mutant mice, and interestingly, overlap with many of the reproductive changes seen in people with diabetes. The role of circadian function in the maintenance of glucose homeostasis is highlighted by recent studies on animal models of obesity, hypertension , and diabetes. We are further investigating metabolic changes and other effects of abnormal circadian rhythm in MageJ2-null mice to understand how changes in circadian function can affect hypothalamic pathways involved in the regulation of reproduction, appetite, and energy balance. This research will characterize an important model linking abnormal circadian function to metabolic and reproductive disturbances. 194 I Increased Pancreatic Islet Glucose-Induced Insulin Secretion in the Prevention of Diabetes Following Voluntary Running Exercise in ZDF Rats. YIYIANE DELGHINGARO-AUGUSTO, SIMON DECARY, JULIEN LAMONTAGNE, HUGUETTE AKAKPO, MARTIN G. LATOUR, MARC PRENTKl, RAYNALD BERGERON', Kinesiologie, Nutrition, CHUM, Universite de Montreal, Montreal, QC. Physical activity improves glycemic control in human subjects suffering from type 2 diabetes (T2DM). However, several studies report either no improvement or a lowering of insulin secretion post- exercise-training. Our aim was to re-evaluate the role of physical activity on insulin secretion and the onset ofT2DM. At 6 wks of age, Zucker Diabetic Fatty (ZDF) and lean (ZL) rats were housed in a wheel cage where they could or not engage in voluntary running exercise for a period of 6 weeks. Sedentary ZDF rats were characterized by progressive hyperglycemia (> 17,0 mM) , hyperlipidemia and marked loss of GSIS. In contrast, physically active ZDF rats maintained nonnoglycemia «8,7 mM) throughout the course of the study. Besides, active ZDF rats presented improved glucose tolerance compared to inactive ZDF rats, which was associated with a 60% increase in plasma insulin (AUC) during OGTT. Physical activity also had beneficial effect on glucose- stimulated insulin secretion and its amp lification by free fatty acids. Besides, active ZDF rat islets had a 60% reduction in the islet triglyceride content, increased expression of the insulin and PDX-I mRNA and up-regulation of genes related 10 fatty acid oxidation (CPT-I and PPARa) when compared to control. [n addition, the expression of the incretin honnone receplOr for GLP I and FFA (GPR40) were increased. We are proposing a new voluntary running exercise training model characterized by complete prevention of hyperglycemia via a significant improvement of GllS. This model will be used to better understand the mechanisms by which exercise training provides protection against p ce ll s dysfunction and diabetes.

Increased Pancreatic Islet Glucose-Induced Insulin Secretion in the Prevention of Diabetes Following Voluntary Running Exercise in ZDF Rats

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POSTER PRESENTATIONS

191 I pnysiolans' Oplhions on Hip fracture preventlon Strategies in Long-term Care ANNA M. SAWKA-' PARMINDER RAINA', SHARON STRAIJS,' NOFISAT ISMAIl-A,' LEHANA THABANE: JONATHAN O. ADACHI, AMIRAM GAFNI 1 ALEXANDRA PAPAIOANNOUi 'university of Toronto, Toronto, ON; 'McMaster University. Hamllton, ON

Design. Senlng. and Par1lclpants: We oonducted a cross, seclional study, collecting data using-a self-administered. wNltel'l quesUonnaire. The su/Vey was mailed on Ap~11, 2008 to 246 Canadian Geriatrlolans In active practice,as well as Ontario Family Physicians belonging to tI1e Ontario Long-term Care Assocfation. We examIned physicians' opinions on the utflfty 01 various hip fracture prevention strategles In tong-term care. Results: Tne results ftom the Rrst65 respondents ere presentee herein but Updated data will be presented at tI1e conference. About two-thirds of respondents were family phySICians (44165) and the rest wele gertatriCians. Most respondents (61/65) performed Clinical war1<. related to the care of elderly residents 01 long-term faCilities. Respondents strongly believed that el f residents 01 long-term care facilities should be targeted for hlp fracture pneventlon strategies (mean 6 .1 Bout 017 on a Likert scale). The majority of respondents very strongly recommended the use of the following strategies In long-term care; calcium, vitamtn 0, oral amfno-blsphasphanates (alandronate or risedronate), physical therapy, and environmental modificatfon (such as hand ralls). The majority did not recommend the use of t/1e follOWing In long-term care; post-menopausal hannone trealmen~ testosterone, or teriperallde, Most respondents either did not recommend or recommended limited use (if other treatments contraindicated or not tolerated) of the folloWing: etldronate, ihtravenaus blsphasphanates, and ralaxi(ene. Support was ml)(ed for hip protectors, B-vltamlns and ,folate. Conclusions: Hlp fracture prevention in long-term care has been identified as an lm~artant priority by Canadian physiCians, Calcl\Jm. Vitamin D, potent oral bisphosphanales and phYSical measures haVe been reoormneflded for LIse in long-term care,

193 I

Study of Adiponectin Level and Adiponectin Gene Mutation in Type 2 Diabetic Patients with Coronary Artery Disease

Yehia M. Ghanem"", Mohamed A. Sobhy""*, Mohamed M. Elsawy***, Mohamed A. Abd Elmohsen* Departments of Diabetes*, Cardiology**, and Clinical Pathology***, Faculty of Medicine, University of Alexandria, Alexandria, Egypt.

Abstract Adiponectin occupies a unique place among adipokines, being the only one having anti-atherogenic, insulin sensitizing, anti-inflammatory, hepato­protective, anti-angiogenic and anti-tumour functions. Several polymorph isms have been identified in the adiponectin gene were found to be associated with low adiponectin levels, features of insulin resistance and CAD. The aim of the present study was to determine the adiponectin level and the frequency of 1164T mutation in the adiponectin gene in type 2 diabetic patients with CAD. The present study included 150 male subjects. They were classified as: Group (1): 100 patients with type 2 DM and CAD. Group (2): 50 control persons with no OM or CAD. All selected individuals were subjected to the following: Full history taking, complete clinical examination laboratory investigation: Fasting serum insulin level and HOMA-IR, Lipid profile, Kidney functions, Serum adiponectin level, DNA extraction & genotyping for detection of polymorphism of 1164T in adiponectin gene. Resting ECG, and Cardiac catheterization and coronary angiography. The results of the present study showed that Group 1 had statistically significant higher mean values of waist circumference, BMI, SB/P, FPG, 2HPPPG. fasting insulin. HbA1c. HOMA·IR. TC. TG. LDL·C. BUN and creatinine but had lower mean value of HDL-C and serum adiponectin, also the frequency of adiponectin gene polymorphism was statistically significantly higher in group 1 than in group 2. Also, there were statistically significant higher mean values between subjects carrying the 1164T mutation than those without the mutation as regard FPG, fasting insulin, HOMA-IR, TC, LDL-C and number of diseased coronary arteries. There was a lower mean va lue of adiponectin level in subjects carrying the 1164T mutation than those without the mutation but with no statistical significance. there was no statistical significant difference between presentation of CAD with either adiponectin level or presence of polymorphism. Also in our study, smokers had a significant lower mean va lue of adiponectin level with no significance difference with incidence of polymorphism. Adiponectin level showed a significant negative correlation with SB/P, DB/P, FPG, 2HPPG, HbA1c, fasting insulin, HOMA-IR, TC, LDL-C, number of diseased coronary arteries and severity of coronary artery stenosis according to gensini score and showed a significant positive correlation with HDL-C.

192 I

MONTREAL 2008 ABSTRACTS I 351

Loss of the Circadian Rhythm Gene Magel2 Leads to Metabolic Changes and Reduced Ferlility in Mice. REBECCA E. MERCER*, and RACHEL WEYRICK, Department of Medical Genetics, University of Alberta, Edmonlon , AB.

We have identified the Prader-Willi Syndrome (PWS) candidate gene MAGEL2 as a circadian output gene rhythmically expressed in the suprachiasmatic nucleus (SCN) of the hypothalamus in mice. People with PWS have profound metabolic disturbances, beginning with a period of poor growth as infants, followed by childhood­onset hyperphagia , which in the absence of strict intervention leads to morbid obesity, insulin resistance, type 2 diabetes, and cardiovascular disease. Those with PWS also manifest reproducti ve difficulties, including delayed and incomplete puberty, sporadic menses , and infertility. The combined features of PWS directly link a genetic defect to primary hypothalamic dysfunction. The proposed roles of circadian rhythm in the maintenance of energy balance and reproductive fitness prompted us to examine these functions in mice lacking Magel2, referred to as Magei2-null.

The Magel2~null mice recapitulate several growth phenotypes of PWS, including an early failure-to~thrive followed by increased weight gain and adiposity following weaning. Magef2-null mice also display abnormal feeding patterns, including reduced food intake, a shift in the timing of food consumption, and an aversion to novel food sources. Reproductive alterations, including a delay in puberty, delay in time-to-mating, early decline in fertility, abnormal estrous cycles , and reduced testosterone levels are consistently observed in Magel2-null mice. These changes are similar to those observed in other circadian mutant mice, and interestingly, overlap with many of the reproductive changes seen in people with diabetes.

The role of circadian function in the maintenance of glucose homeostasis is highlighted by recent studies on animal models of obesity , hypertension , and diabetes. We are further investigating metabolic changes and other effects of abnormal circadian rhythm in MageJ2-null mice to understand how changes in circadian function can affect hypothalamic pathways involved in the regulation of reproduction, appetite , and energy balance. This research will characterize an important model linking abnormal circadian function to metabolic and reproductive disturbances.

194 I Increased Pancreatic Islet Glucose-Induced Insulin Secretion in the Prevention of Diabetes Following Voluntary Running Exercise in ZDF Rats.

YIYIANE DELGHINGARO-AUGUSTO, SIMON DECARY, JULIEN LAMONTAGNE, HUGUETTE AKAKPO, MARTIN G. LATOUR, MARC PRENTKl, RAYNALD BERGERON', Kinesiologie, Nutrition, CHUM, Universite de Montreal, Montreal, QC.

Physical activity improves glycemic control in human subjects suffering from type 2 diabetes (T2DM). However, several studies report either no improvement or a lowering of insulin secretion post­exercise-training. Our aim was to re-evaluate the role of physical activity on insulin secretion and the onset ofT2DM. At 6 wks of age, Zucker Diabetic Fatty (ZDF) and lean (ZL) rats were housed in a wheel cage where they could or not engage in voluntary running exercise for a period of 6 weeks. Sedentary ZDF rats were characterized by progressive hyperglycemia (> 17,0 mM), hyperlipidemia and marked loss of GSIS. In contrast, physically active ZDF rats maintained nonnoglycemia «8,7 mM) throughout the course of the study. Besides, active ZDF rats presented improved glucose tolerance compared to inactive ZDF rats, which was associated with a 60% increase in plasma insulin (AUC) during OGTT. Physical activity also had beneficial effect on glucose­stimulated insulin secretion and its amp lification by free fatty acids. Besides, active ZDF rat islets had a 60% reduction in the islet triglyceride content, increased expression of the insulin and PDX-I mRNA and up-regulation of genes related 10 fatty acid oxidation (CPT-I and PPARa) when compared to control. [n addition, the expression of the incretin honnone receplOr for GLP I and FF A (GPR40) were increased.

We are proposing a new voluntary running exercise training model characterized by complete prevention of hyperglycemia via a significant improvement of GllS. This model will be used to better understand the mechanisms by which exercise training provides protection against p cell s dysfunction and diabetes.