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Diabetes in Pregnancy Exposure, Mitochondrial Markers, and Diastolic Function in Adolescents with Type 2 Diabetes
Abstracts / Can J Diabetes 41 (2017) S2–S16
37 Body Weight and Energy Intake Changes in Overweight Individuals Treated with Canagliflozin, Phentermine, or Canagliflozin+Phentermine DAVID POLIDOR, NATHAN GILL, FRANK VERCRUYSSE, NGOZI ERONDU, KEVIN D. HALL San Diego, CA SGLT2 inhibitors (SGLT2i) induce a caloric loss by increasing urinary glucose excretion (UGE) leading to a modest yet sustained weight loss (WL) of ~2-4% in patients with type 2 diabetes. This WL is much less than predicted based on the UGE caloric deficit alone due to compensatory increases in energy intake (EI) that occur in response to WL. A 26-week study in overweight, otherwise healthy individuals (N=334, 82% female, mean (SD) age=46 (11) y, body weight (BW)=103 (18) kg, BMI=37 (5) kg/m2) tested the hypothesis that combining the appetite suppressant phentermine (PHEN 15 mg) with the SGLT2i canagliflozin (CANA 300 mg) results in greater WL than either monotherapy. Changes in EI were estimated using a previously validated mathematical model of energy balance using measured BW profiles and an estimated UGE of 55 g/day with CANA. As expected, WL was greatest with CANA+PHEN, and estimated EI was increased with CANA and decreased with PHEN (Figure). Surprisingly, despite the greater WL with CANA+PHEN, EI with CANA+PHEN was virtually identical to EI with PHEN alone, suggesting that co-administration of PHEN was able to fully block the compensatory EI increase that occurs with CANA alone. This effect led to greater-than-additive WL with CANA+PHEN, and individuals were still in negative energy balance and losing weight at Week 26. Longer-term studies with CANA+PHEN are warranted.
38 Diabetes in Pregnancy Exposure, Mitochondrial Markers, and Diastolic Function in Adolescents with Type 2 Diabetes LAETITIA GUILLEMETTE*, ALLISON DART, BRANDY WICKLOW, VERNON W. DOLINSKY, DAVINDER JASSAL, ELIZABETH SELLERS, TODD A. DUHAMEL, JONATHAN MCGAVOCK Winnipeg, MB Purpose: Mitochondrial dysfunction is intimately linked to type 2 diabetes (T2D) and cardiovascular disease (CVD). We hypothesized that exposure to diabetes in pregnancy (DiP) would adversely affect mitochondrial function and CVD risk in youth with T2D. Methods: We analysed serum metabolomic markers of mitochondrial function/oxidative stress (ultra-performance liquid chromatography-tandem mass spectroscopy) as well as cardiac diastolic function (echocardiography-measured left ventricular earlyto-late [E/A] blood flow velocity) in youth with T2D. DiP exposure was classified as T2D (n=34), gestational diabetes (n=16), and normoglycemia (NG; n=38). Significance was set at q (p-value adjusted for false discovery rate)<0.05. Results: Groups were similar for sex (62 vs 43 vs 71% female), age (14.8±2.7 vs 15.4±2.8 vs 15.4±2.6 years), duration of diabetes (3.0, [interquartile range]: [2.0–5.0] vs 2.0 [1.0–3.5] vs 3.0 [2.0–5.0]years),
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fat% (30±10 vs 31±10 vs 33±13%) and systolic blood pressure load (45 [22–74] vs 42 [24–53] vs 33 [19–61]%). DiP exposure was not associated with metabolomic markers of mitochondrial function but worsened oxidative stress (hydroxyoctadecadienoic acids [13-/9HODE]; T2D/NG ratio=2.20, q=0.02; methionine sulfoxide T2D/NG ratio=2.06, q=0.01). Mitochondrial metabolomic markers were not associated with diastolic function (leucine: r=−0.23, q=0.08; isoleucine: r=−0.25, q=0.06; valine: r=−0.22, q=0.09; carnitine: r=0.19, q=0.13). Oxidative stress was inversely associated with diastolic function (13-/9-HODE: r=−0.23, q=0.08; methionine sulfoxide: r=−0.23, q=0.08). Conclusion: Oxidative stress, but not mitochondrial dysfunction, is associated with DiP exposure and impaired diastolic function in adolescents with T2D.
39 Parental Decision-Making Processes in Pediatric Trial Enrollment: Recommendations for Informed Consent in Juvenile Type 1 Diabetes Research STEPHANIE KOWAL*, TANIA BUBELA Edmonton, AB Background: Clinical trials for novel interventions, including cell therapies and devices, for Type 1 diabetes are beginning to recruit pediatric participants. It is, therefore timely to consider how to communicate risks and potential benefits of trial participation with parents who make clinical decisions on behalf of their child. Parents have high expectations for new treatment options, which may encourage them to pursue clinical trial opportunities or join risky movements. For example, the Do It Yourself Pancreas System uses open access coding communities to share unproven automated insulin delivery via smartphones. Methods: We conducted 16 qualitative interviews with parents of children with Type 1 diabetes to explore information gathering, decision-making processes, and knowledge of clinical trial conduct by parents. We used the constant comparison method to code interview transcripts for themes, using NVivo qualitative analysis software. Results: Parents’ decision-making processes followed Protection Motivation Theory. This theory posits that parents will use available information to balance the risks of trial participation against the risks of current disease management. This balancing helps them decide whether trial enrollment may protect the health of their child better than current management methods. However, the Theory needs to account for the overly optimistic information about treatment research accessed by parents on traditional and social media. In general, parents are risk-adverse and express a preference for complete and accurate information to make fully informed decisions. Conclusion: Parents can differentiate between hope and expectation for trial outcomes. However, their preference for accurate information means that clinicians must clearly communicate therapeutic potential, likelihoods of risks and benefits, as well as uncertainty. Recommendations for clinical investigators to develop communication protocols that ensure parents receive all necessary risk and benefit information will ensure that parental consent for pediatric clinical trials is, in fact, informed. 40 Exposure to Adverse Child Experiences Increase the Odds of Obesity in Early Adolescence: A Population-Based Prospective Cohort Study RACHEL GARDNER, ALLISON FEELY, JON MCGAVOCK Winnipeg, MB
37 Body Weight and Energy Intake Changes in Overweight Individuals Treated with Canagliflozin, Phentermine, or Canagliflozin+Phentermine DAVID POLIDOR, NATHAN GILL, FRANK VERCRUYSSE, NGOZI ERONDU, KEVIN D. HALL San Diego, CA SGLT2 inhibitors (SGLT2i) induce a caloric loss by increasing urinary glucose excretion (UGE) leading to a modest yet sustained weight loss (WL) of ~2-4% in patients with type 2 diabetes. This WL is much less than predicted based on the UGE caloric deficit alone due to compensatory increases in energy intake (EI) that occur in response to WL. A 26-week study in overweight, otherwise healthy individuals (N=334, 82% female, mean (SD) age=46 (11) y, body weight (BW)=103 (18) kg, BMI=37 (5) kg/m2) tested the hypothesis that combining the appetite suppressant phentermine (PHEN 15 mg) with the SGLT2i canagliflozin (CANA 300 mg) results in greater WL than either monotherapy. Changes in EI were estimated using a previously validated mathematical model of energy balance using measured BW profiles and an estimated UGE of 55 g/day with CANA. As expected, WL was greatest with CANA+PHEN, and estimated EI was increased with CANA and decreased with PHEN (Figure). Surprisingly, despite the greater WL with CANA+PHEN, EI with CANA+PHEN was virtually identical to EI with PHEN alone, suggesting that co-administration of PHEN was able to fully block the compensatory EI increase that occurs with CANA alone. This effect led to greater-than-additive WL with CANA+PHEN, and individuals were still in negative energy balance and losing weight at Week 26. Longer-term studies with CANA+PHEN are warranted.
38 Diabetes in Pregnancy Exposure, Mitochondrial Markers, and Diastolic Function in Adolescents with Type 2 Diabetes LAETITIA GUILLEMETTE*, ALLISON DART, BRANDY WICKLOW, VERNON W. DOLINSKY, DAVINDER JASSAL, ELIZABETH SELLERS, TODD A. DUHAMEL, JONATHAN MCGAVOCK Winnipeg, MB Purpose: Mitochondrial dysfunction is intimately linked to type 2 diabetes (T2D) and cardiovascular disease (CVD). We hypothesized that exposure to diabetes in pregnancy (DiP) would adversely affect mitochondrial function and CVD risk in youth with T2D. Methods: We analysed serum metabolomic markers of mitochondrial function/oxidative stress (ultra-performance liquid chromatography-tandem mass spectroscopy) as well as cardiac diastolic function (echocardiography-measured left ventricular earlyto-late [E/A] blood flow velocity) in youth with T2D. DiP exposure was classified as T2D (n=34), gestational diabetes (n=16), and normoglycemia (NG; n=38). Significance was set at q (p-value adjusted for false discovery rate)<0.05. Results: Groups were similar for sex (62 vs 43 vs 71% female), age (14.8±2.7 vs 15.4±2.8 vs 15.4±2.6 years), duration of diabetes (3.0, [interquartile range]: [2.0–5.0] vs 2.0 [1.0–3.5] vs 3.0 [2.0–5.0]years),
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fat% (30±10 vs 31±10 vs 33±13%) and systolic blood pressure load (45 [22–74] vs 42 [24–53] vs 33 [19–61]%). DiP exposure was not associated with metabolomic markers of mitochondrial function but worsened oxidative stress (hydroxyoctadecadienoic acids [13-/9HODE]; T2D/NG ratio=2.20, q=0.02; methionine sulfoxide T2D/NG ratio=2.06, q=0.01). Mitochondrial metabolomic markers were not associated with diastolic function (leucine: r=−0.23, q=0.08; isoleucine: r=−0.25, q=0.06; valine: r=−0.22, q=0.09; carnitine: r=0.19, q=0.13). Oxidative stress was inversely associated with diastolic function (13-/9-HODE: r=−0.23, q=0.08; methionine sulfoxide: r=−0.23, q=0.08). Conclusion: Oxidative stress, but not mitochondrial dysfunction, is associated with DiP exposure and impaired diastolic function in adolescents with T2D.
39 Parental Decision-Making Processes in Pediatric Trial Enrollment: Recommendations for Informed Consent in Juvenile Type 1 Diabetes Research STEPHANIE KOWAL*, TANIA BUBELA Edmonton, AB Background: Clinical trials for novel interventions, including cell therapies and devices, for Type 1 diabetes are beginning to recruit pediatric participants. It is, therefore timely to consider how to communicate risks and potential benefits of trial participation with parents who make clinical decisions on behalf of their child. Parents have high expectations for new treatment options, which may encourage them to pursue clinical trial opportunities or join risky movements. For example, the Do It Yourself Pancreas System uses open access coding communities to share unproven automated insulin delivery via smartphones. Methods: We conducted 16 qualitative interviews with parents of children with Type 1 diabetes to explore information gathering, decision-making processes, and knowledge of clinical trial conduct by parents. We used the constant comparison method to code interview transcripts for themes, using NVivo qualitative analysis software. Results: Parents’ decision-making processes followed Protection Motivation Theory. This theory posits that parents will use available information to balance the risks of trial participation against the risks of current disease management. This balancing helps them decide whether trial enrollment may protect the health of their child better than current management methods. However, the Theory needs to account for the overly optimistic information about treatment research accessed by parents on traditional and social media. In general, parents are risk-adverse and express a preference for complete and accurate information to make fully informed decisions. Conclusion: Parents can differentiate between hope and expectation for trial outcomes. However, their preference for accurate information means that clinicians must clearly communicate therapeutic potential, likelihoods of risks and benefits, as well as uncertainty. Recommendations for clinical investigators to develop communication protocols that ensure parents receive all necessary risk and benefit information will ensure that parental consent for pediatric clinical trials is, in fact, informed. 40 Exposure to Adverse Child Experiences Increase the Odds of Obesity in Early Adolescence: A Population-Based Prospective Cohort Study RACHEL GARDNER, ALLISON FEELY, JON MCGAVOCK Winnipeg, MB