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Physical Activity Intensity and Adiposity in Obese Youth: The POWER Trial
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Abstracts / Can J Diabetes 37 (2013) S6eS11
Methods: Adolescents (n¼304, age 14 to 18 years, BMI >85th percentile) were randomized to aerobic exercise (A), resistance exercise (R), both (A+R)d4 times per weekdor control (C). The primary outcome was % body fat (%BF) by MRI at 6 months. Primary analyses were intention to treat. Per-protocol analyses included only subjects (n¼163) completing 70% of prescribed exercise (2.8 sessions/week). Results: Percent body fat and waist circumference decreased in all exercise groups (p<0.001) but not C. Absolute %BF decreases were 1.1% in A (p¼0.06 vs. C), 1.6% in R (p¼0.002 vs. C), 1.4% in A+R (p¼0.007 vs. C) and 0.4% in C. Waist circumference decreased 3.1 cm in A (p¼0.012 vs. C), 2.2 cm in R (NS vs. C), 4.2 cm in A+R (p¼0.013 vs. R, p¼0.13 vs. A, p<0.001 vs. C) and 0.4 cm in C. In perprotocol analyses, %BF decreased 1.2% in A, 1.7% in R, 2.4% in A+R (p¼0.036 vs. A, p<0.001 vs. C) and 0.3% in C, and waist circumference decreased 3.7 cm in A, 4.5 cm in R, 6.8 cm in A+R ( p¼0.013 vs. R, p<0.001 vs. C) and 0.6 cm in C. Changes in lipids, blood pressure and glucose tolerance did not differ among groups. Conclusions: Six months of aerobic, resistance or combined training reduced percent body fat and waist circumference significantly. Combined training was superior to aerobic or resistance training when performed regularly.
16 Physical Activity Intensity and Adiposity in Obese Youth: The POWER Trial JONATHAN M. MCGAVOCK*, JACQUELINE HAY, TODD DUHAMEL, BRANDY WICKLOW, HEATHER DEAN, ELIZABETH SELLERS, ELIZABETH READY, LORI BERARD Winnipeg, MB Background: The rate of diabetes in individuals with serious mental illness is 2 to 3 times the general population rate. Diabetic co-morbidities are also higher in this population. The most severely affected often reside in board and care homes, managed by nonprofessional staff. We studied the effects of training these staff in behavioural techniques for weight loss. Methods: Staff of 5 board and care homes were recruited to participate in a year-long program to improve nutrition and physical activities for residents. The subjects were 18 residents who had type 2 diabetes mellitus and a psychotic illness. The primary outcome was change in weight from baseline to the end of the study. Research staff recorded the participants’ weights. All other aspects of the intervention were taught to and carried out by the staff of the homes. Results: In initial focus groups, staff expressed pessimism about persuading residents to change their behaviour, but still agreed to participate. Baseline and endpoint data from 18 subjects showed weight was lost by all except 3 subjects (mean weight loss 6.73 kg; 95% (CI e9.93 to e3.53 kg); p less than 0.001 [t¼4.44; df¼17]). Conclusions: Despite the initial pessimism of the staff, almost all the subjects lost weight. Since the intervention was delivered by the existing staff of the residential facilities, there was minimal increase of cost to the system. The quasi-experimental design of the study is a limitation, but these encouraging results should justify a rigorous randomized controlled trial of the intervention in similar settings.
17 Weight Loss Intervention for Individuals with Diabetes and Serious Mental Illness: A Pragmatic Experiment in Community Settings ROHAN GANGULI*, TODD JENKINS, KINNON MACKINNON, MEHREEN BHAMANI Toronto, ON Metabolic syndrome and type 2 diabetes are increasingly prevalent global health risks. The transition from glucose intolerance/
prediabetes to a diagnosis of diabetes occurs when pancreatic beta cells fail to compensate for the increasing demand for insulin. While mechanisms for increasing beta cell mass have been described, the molecular underpinnings of beta cell functional compensation remain largely unknown. Here we delineate a novel pathway featuring the Ser/Thr protein kinase Sik2 and E3 ubiqutin ligase Pja2 that is harnessed by the beta cell in both rodents and humans to enhance insulin secretion in response to hyperglycemia. Sik2 phosphorylates p35 at Ser91 to trigger p35 degradation by Pja2, which promotes insulin secretion through activation of voltage-dependent calcium channel (VDCC) and calcium ion influx. Loss of Sik2 in beta cells exacerbates high-fat diet-induced glucose intolerance, due to decreased plasma insulin levels. Sik2 protein accumulates in beta cells of obese models and human obese subjects, and is stabilized upon exposure to high concentration of glucose. Enhanced insulin secretion in islets from obese model mice is reverted by Sik2 knockdown. These findings demonstrate that the Sik2-Pja2-p35 complex is critical for beta cell functional compensation and maintenance of glucose homeostasis.
18 Inhibition of Insulin-Stimulated Glucose Transport by Amino Acids in Muscle Cells is Not Unique to Leucine PEGAH TAVAJOHI-FINI, OLASUNKANMI J. ADEGOKE* Toronto, ON Insulin resistance is a predisposing factor to type 2 diabetes and cardiovascular disease. High protein diets are sometimes prescribed in weight management interventions; however, these diets and amino acids (AA) have been linked to insulin resistance. Much of the attention has been on the branched chain amino acid (BCAA) leucine because of its ability to activate the mammalian target of rapamycin complex 1 (mTORC1). This complex and its substrate (S6K1) are implicated in AA-induced insulin resistance due to their inhibitory serine phosphorylation of insulin receptor substrate 1 (IRS1). Since AAs other than leucine are present in dietary proteins, we examined their roles. Valine suppressed insulin-stimulated glucose uptake (Glu-trans) in L6 myotubes by 47% (p<0.05) compared to a suppression of 22% observed with leucine. The effect was not due to a greater intracellular accumulation of valine. However, valine and leucine increased phosphorylation of S6K1 (thr389) and IRS1 (ser612 [p<0.05]); isoleucine had no effect on these. This is consistent with a lack of effect of isoleucine on Glutrans. We also examined the effect of 2 metabolites of leucine, ketoisocaproic acid (KIC) and isovaleryl CoA. KIC, but not isovaleryl CoA, suppressed Glu-trans by 25% (p<0.05) and increased S6K1 and IRS1 phosphorylation. Strikingly, AA other than the BCAA, especially arginine and glutamine, also suppressed Glu-trans by 22 to 47% (p<0.05). Inhibition of Glu-trans was not always linked to mTORC1/S6K1 and IRS1 phosphorylation. We conclude that AA other than leucine can induce insulin resistance of glucose transport via mechanism other than those employed by the BCAA.
19 A Population-Based Study of Diabetes Incidence by Ethnicity and Age: Support for the Development of Ethnic-Specific Screening and Prevention Strategies MARIA I. CREATORE*, GILLIAN L. BOOTH, RAHIM MOINEDDIN, DOUG MANUEL, RICHARD H. GLAZIER Toronto, ON; Ottawa, ON Background: Diabetes risk is higher in certain ethnic groups, and this risk may begin at a younger age, particularly among South Asians. Current clinical guidelines are not clear about the optimal age at which to initiate screening in high-risk populations. Methods: We conducted a longitudinal, population-based, retrospective cohort study using linked administrative health and
Abstracts / Can J Diabetes 37 (2013) S6eS11
Methods: Adolescents (n¼304, age 14 to 18 years, BMI >85th percentile) were randomized to aerobic exercise (A), resistance exercise (R), both (A+R)d4 times per weekdor control (C). The primary outcome was % body fat (%BF) by MRI at 6 months. Primary analyses were intention to treat. Per-protocol analyses included only subjects (n¼163) completing 70% of prescribed exercise (2.8 sessions/week). Results: Percent body fat and waist circumference decreased in all exercise groups (p<0.001) but not C. Absolute %BF decreases were 1.1% in A (p¼0.06 vs. C), 1.6% in R (p¼0.002 vs. C), 1.4% in A+R (p¼0.007 vs. C) and 0.4% in C. Waist circumference decreased 3.1 cm in A (p¼0.012 vs. C), 2.2 cm in R (NS vs. C), 4.2 cm in A+R (p¼0.013 vs. R, p¼0.13 vs. A, p<0.001 vs. C) and 0.4 cm in C. In perprotocol analyses, %BF decreased 1.2% in A, 1.7% in R, 2.4% in A+R (p¼0.036 vs. A, p<0.001 vs. C) and 0.3% in C, and waist circumference decreased 3.7 cm in A, 4.5 cm in R, 6.8 cm in A+R ( p¼0.013 vs. R, p<0.001 vs. C) and 0.6 cm in C. Changes in lipids, blood pressure and glucose tolerance did not differ among groups. Conclusions: Six months of aerobic, resistance or combined training reduced percent body fat and waist circumference significantly. Combined training was superior to aerobic or resistance training when performed regularly.
16 Physical Activity Intensity and Adiposity in Obese Youth: The POWER Trial JONATHAN M. MCGAVOCK*, JACQUELINE HAY, TODD DUHAMEL, BRANDY WICKLOW, HEATHER DEAN, ELIZABETH SELLERS, ELIZABETH READY, LORI BERARD Winnipeg, MB Background: The rate of diabetes in individuals with serious mental illness is 2 to 3 times the general population rate. Diabetic co-morbidities are also higher in this population. The most severely affected often reside in board and care homes, managed by nonprofessional staff. We studied the effects of training these staff in behavioural techniques for weight loss. Methods: Staff of 5 board and care homes were recruited to participate in a year-long program to improve nutrition and physical activities for residents. The subjects were 18 residents who had type 2 diabetes mellitus and a psychotic illness. The primary outcome was change in weight from baseline to the end of the study. Research staff recorded the participants’ weights. All other aspects of the intervention were taught to and carried out by the staff of the homes. Results: In initial focus groups, staff expressed pessimism about persuading residents to change their behaviour, but still agreed to participate. Baseline and endpoint data from 18 subjects showed weight was lost by all except 3 subjects (mean weight loss 6.73 kg; 95% (CI e9.93 to e3.53 kg); p less than 0.001 [t¼4.44; df¼17]). Conclusions: Despite the initial pessimism of the staff, almost all the subjects lost weight. Since the intervention was delivered by the existing staff of the residential facilities, there was minimal increase of cost to the system. The quasi-experimental design of the study is a limitation, but these encouraging results should justify a rigorous randomized controlled trial of the intervention in similar settings.
17 Weight Loss Intervention for Individuals with Diabetes and Serious Mental Illness: A Pragmatic Experiment in Community Settings ROHAN GANGULI*, TODD JENKINS, KINNON MACKINNON, MEHREEN BHAMANI Toronto, ON Metabolic syndrome and type 2 diabetes are increasingly prevalent global health risks. The transition from glucose intolerance/
prediabetes to a diagnosis of diabetes occurs when pancreatic beta cells fail to compensate for the increasing demand for insulin. While mechanisms for increasing beta cell mass have been described, the molecular underpinnings of beta cell functional compensation remain largely unknown. Here we delineate a novel pathway featuring the Ser/Thr protein kinase Sik2 and E3 ubiqutin ligase Pja2 that is harnessed by the beta cell in both rodents and humans to enhance insulin secretion in response to hyperglycemia. Sik2 phosphorylates p35 at Ser91 to trigger p35 degradation by Pja2, which promotes insulin secretion through activation of voltage-dependent calcium channel (VDCC) and calcium ion influx. Loss of Sik2 in beta cells exacerbates high-fat diet-induced glucose intolerance, due to decreased plasma insulin levels. Sik2 protein accumulates in beta cells of obese models and human obese subjects, and is stabilized upon exposure to high concentration of glucose. Enhanced insulin secretion in islets from obese model mice is reverted by Sik2 knockdown. These findings demonstrate that the Sik2-Pja2-p35 complex is critical for beta cell functional compensation and maintenance of glucose homeostasis.
18 Inhibition of Insulin-Stimulated Glucose Transport by Amino Acids in Muscle Cells is Not Unique to Leucine PEGAH TAVAJOHI-FINI, OLASUNKANMI J. ADEGOKE* Toronto, ON Insulin resistance is a predisposing factor to type 2 diabetes and cardiovascular disease. High protein diets are sometimes prescribed in weight management interventions; however, these diets and amino acids (AA) have been linked to insulin resistance. Much of the attention has been on the branched chain amino acid (BCAA) leucine because of its ability to activate the mammalian target of rapamycin complex 1 (mTORC1). This complex and its substrate (S6K1) are implicated in AA-induced insulin resistance due to their inhibitory serine phosphorylation of insulin receptor substrate 1 (IRS1). Since AAs other than leucine are present in dietary proteins, we examined their roles. Valine suppressed insulin-stimulated glucose uptake (Glu-trans) in L6 myotubes by 47% (p<0.05) compared to a suppression of 22% observed with leucine. The effect was not due to a greater intracellular accumulation of valine. However, valine and leucine increased phosphorylation of S6K1 (thr389) and IRS1 (ser612 [p<0.05]); isoleucine had no effect on these. This is consistent with a lack of effect of isoleucine on Glutrans. We also examined the effect of 2 metabolites of leucine, ketoisocaproic acid (KIC) and isovaleryl CoA. KIC, but not isovaleryl CoA, suppressed Glu-trans by 25% (p<0.05) and increased S6K1 and IRS1 phosphorylation. Strikingly, AA other than the BCAA, especially arginine and glutamine, also suppressed Glu-trans by 22 to 47% (p<0.05). Inhibition of Glu-trans was not always linked to mTORC1/S6K1 and IRS1 phosphorylation. We conclude that AA other than leucine can induce insulin resistance of glucose transport via mechanism other than those employed by the BCAA.
19 A Population-Based Study of Diabetes Incidence by Ethnicity and Age: Support for the Development of Ethnic-Specific Screening and Prevention Strategies MARIA I. CREATORE*, GILLIAN L. BOOTH, RAHIM MOINEDDIN, DOUG MANUEL, RICHARD H. GLAZIER Toronto, ON; Ottawa, ON Background: Diabetes risk is higher in certain ethnic groups, and this risk may begin at a younger age, particularly among South Asians. Current clinical guidelines are not clear about the optimal age at which to initiate screening in high-risk populations. Methods: We conducted a longitudinal, population-based, retrospective cohort study using linked administrative health and