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Identification of Novel Adipogenic Factors in the 14–3-3ζ Interactome During Adipocyte Differentiation
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Abstracts / Can J Diabetes 41 (2017) S22–S83
on dispersed human islets from healthy donors and donors with T2D. Results: mRNA analysis of glycine receptors α1 subunit reveal splice variation producing Glycine receptor α1 variant 1 and Glycine receptor α1 variant 3 (henceforth referred to as variant 1 and variant 3 respectively), where variant 1 is the full length protein while variant 3 contains a truncation on the N-terminus. Plasmids for both variant 1 and variant 3 were created and transfected into HEK cells. Variant 3 is unable to produce a current when stimulated with 300uM glycine. Molecular dynamic modeling of the receptor was employed to further study the structural differences between variant 1 and variant 3. Binding analysis demonstrated that glycine cannot bind to the binding site in variant 3. We suspect that variant 3 maybe upregulated in T2D and may explain the reduced glycine current associated with T2D and increased plasma glucose concentration. Conclusion: glycine receptor mediated current is known to be reduced in islets from human donors with T2D compared to human donors without T2D. Although insulin resistance is suspected to play a role in the reduced glycine current, our evidence suggests that upregulation of a non-functional receptor variant 3 may also contribute to reduced glycine current. 193 Gestational Diabetes Mellitus (GDM) Exposure and Postnatal Diet Influence Pancreatic Islet Function of the Rat Offspring TAYLOR MORRISEAU, NAVDEEP BRAR, PRASOON AGARWAL, MARIO FONSECA, STEPHANIE KERELIUK, LAURA COLEBO XIANG, NIVEDITA SESHADRI, KRISTIN HUNT, GRANT HATCH, CHRISTINE DOUCETTE, VERNON DOLINSKY Winnipeg, MB Introduction: As the obesity epidemic worsens, GDM rates are rapidly increasing. GDM exposure and obesity are strong risk factors for type 2 diabetes (T2D) development; however, the connections between GDM exposure, postnatal diet and islet dysfunction in offspring metabolic health remain unclear. Hypothesis: GDM exposure alters gene expression in islets and impairs beta cell function, which is worsened by a postnatal highfat and sucrose (HFS) diet. Methods: GDM was induced in female rats using a HFS diet, according to our established protocol. Litters of LEAN or GDM dams were divided and pups were weaned onto a low-fat (LF) or HFS diet. Pancreata and islets were isolated from 15-week-old offspring to analyze pancreas morphology, gene expression (RNA-seq), glucosestimulated insulin secretion (GSIS), and insulin content. Results: GDM exposure reduced GSIS by 15%, which was exacerbated by postnatal HFS exposure (85% GSIS reduction). Beta cell mass was reduced 2-fold from GDM exposed and HFS-fed offspring, compared to GDM-exposed LF-fed offspring. Islets from LF-fed GDM-exposed offspring exhibited 93 upregulated genes (including Il-6, Ppp1r3a, and Angptl4) and 30 downregulated genes. In the GDM-exposed HFS-diet group, a unique set of 510 genes (including Cel and Rbp4) were upregulated and 174 genes were downregulated. Conclusion: GDM exposure followed by postnatal over-nutrition additively impair islet function and induce greater changes in gene expression. Together, our findings suggest that GDM exposure and post-natal diet cumulatively interact to worsen metabolic health outcomes in offspring. 194 A Case of Hypertriglycideremia-induced Pancreatitis in Diabetic Ketoacidosis AURELIE PARE*, MICHAEL TSOUKAS Montreal, QC
Figure 1. Evolution of Triglyceride Level in Response to Insulin Therapy.
Clinical Presentation: An 54 year-old female known for poorly controlled diabetes mellitus type 2 presented to the emergency room for vomiting. She was found to have diabetic ketoacidosis (DKA) and hypertriglyceridemia. Computed tomography of the abdomen revealed grade D pancreatitis. Clinical Outcome: The patient’s pancreatitis was believed to be secondary to hypertriglyceridemia in the context of DKA. The patient was known for a similar episode having occurred one year prior. She improved following treatment of hypertriglyceridemia with intravenous insulin. Discussion: Hypertriglyceridemia causing acute pancreatitis is a known complication of DKA, having been previously reported in case reports and further examined in retrospective cohort studies of patients presenting with DKA. The pathophysiology, clinical presentation, and treatment of this condition are explored. Conclusion: Hypertriglyceridemia-induced pancreatitis associated with DKA is an uncommon entity that can present a diagnostic challenge for clinicians. 195 Identification of Novel Adipogenic Factors in the 14–3-3ζ Interactome During Adipocyte Differentiation YVES MUGABO, JASON T. LEE, NANCY N. FANG, AMPARO ACKER-PALMER, THIBAULT MAYOR, JAMES D. JOHNSON, GARETH E. LIM Repentigny, QC Adipogenesis involves a signaling network that requires strict temporal and spatial organization of effector molecules. We previously identified critical roles for the 14–3-3 protein family, and in particular 14–3-3ζ, as an essential upstream factor in adipocyte differentiation. 14–3-3ζ interact with diverse proteins to form its interactome suggesting that it can regulate several cellular processes that may be involved in adipogenesis. Thus, determining this interactome may help in further understanding the regulatory roles of 14–3-3ζ on adipocyte differentiation. Mouse embryonic fibroblasts from TAP-epitope-tagged 14–3-3ζ transgenic mice were generated, followed by an unbiased proteomic analysis to determine how adipocyte differentiation influences the 14–3-3ζ interactome. Interacting proteins were categorized using gene ontology and their role in adipogenesis, as assessed by Oil Red-O incorporation or quantitative PCR, were evaluated with a functional siRNA screen in 3T3-L1 cells. Proteomic analysis of the 14–3-3ζ interactome identified over 120 proteins that were unique to adipocyte differentiation. An enrichment of proteins related to RNA metabolism, processing, and splicing were found in the differentiation-associated interactome. Our screening approach revealed essential roles for RNA splicing-related proteins, Hnrnpf, Hnrnpk, Ddx6, and Sfpq in adipogenesis. This study demonstrates the ability of identifying novel adipogenic factors within the 14–3-3ζ interactome and reveals alternative path-
Abstracts / Can J Diabetes 41 (2017) S22–S83
ways and processes that may be facilitated by 14–3-3ζ during differentiation. Determining the interactome of 14–3-3 proteins may help in the discovery of novel therapeutic targets for obesity and type 2 diabetes treatments. 196 The Effect of Carbohydrate Restriction at Breakfast on Glycemic Control in Type 2 Diabetes. COURTNEY CHANG, MONIQUE FRANCOIS, JONATHAN LITTLE Kelowna, BC Purpose: To examine the effect of consuming a low-carbohydrate breakfast on postprandial and 24-hour blood glucose responses to mixed meals in individuals with type 2 diabetes (T2D). Methods: Adults with physician-diagnosed T2D (N=21, 60±10y, A1c: 6.7±0.7%, BMI: 31.6±7kg/m2) completed two 24-h isocaloric intervention periods, in a random order. Participants consumed either i) a low-carbohydrate breakfast (LC-BF; <10%CHO/85%FAT/15%PRO) or ii) a breakfast with dietary guidelines recommended nutrient profile (GL-BF; 55%CHO/ 30%FAT/ 15%PRO), with the same lunch and dinner provided (both 55%CHO/ 30%FAT/ 15%PRO). Continuous glucose monitoring was used to assess postprandial glucose responses to each meal (incremental area under the curve; iAUC) and the mean 24-h glucose during each intervention. Results: The postprandial glucose excursion (3 h iAUC) after the LC-BF was 80% lower than the GL-BF (p<0.01). Overall postprandial hyperglycemia, measured as the postmeal iAUC sum of breakfast, lunch and dinner, was significantly reduced with the LC-BF compared to the GL-BF (−69±104 mmol/L* 9 h, p=0.01). However, the mean 24-h blood glucose (LC-BF: 7.2±1 mmol/L vs GL-BF: 7.3±1.3 mmol/L, p=0.77) and glycemic variability were not significantly lower with the LC-BF (mean amplitude of glycemic excursions [MAGE]: LC-BF: 3.2±1.3 mmol/L vs GL-BF: 3.4±1.3 mmol/L). Conclusion: Restricting carbohydrate at breakfast reduces postprandial hyperglycemia in individuals with T2D. A low-carbohydrate breakfast may be a simple and effective strategy to reduce the development of diabetes complications in T2D and long-term interventions are warranted. 197 The Effect of a Short-term Low-carbohydrate Diet on Markers of Beta-cell Function in Type 2 Diabetes ÉTIENNE MYETTE-CÔTÉ, HELENA NEUDORF, CODY DURRER, JONATHAN P. LITTLE Kelowna, BC Aim: To determine if lowering glucose using a short-term lowcarbohydrate high-fat diet with (LCHF+PW) or without (LCHF) daily post-meal walks (PW) can improve markers of beta-cell dysfunction when compared to a low-fat dietary guidelines diet (DG) in individuals with type 2 diabetes. Methods: In a pilot study, 6 individuals with T2D (age: 67±7, HbA1c: 6.8±0.6, BMI: 31.8±2.7 means±SD) completed three isocaloric 4-day diet conditions in a randomized crossover design. The LCHF+PW diet included three daily 15-min post meal walks at a light-to-moderate intensity. Continuous glucose monitoring was used across all four days. Fasting blood samples taken before and after each intervention were used to analyze fasting proinsulin, insulin, and proinsulin:insulin ratio. Results: Compared to DG (7.5±0.9, 2.1±1.1 mmol/l), both LCHF (6.5±0.9, 1.1±0.4 mmol/l) and LCHF+PW (6.2±0.9, 1.0±0.4 mmol/l) decreased 4-day mean glucose concentrations (p≤0.001) and glycemic variability (p<0.05). The LCHF (−11.2±6.8 pmol/l) and LCHF+PW conditions (−17.1±11.9 pmol/l) decreased fasting proinsulin (both p≤0.02) whereas no change was observed after DG (−2.8±5.0 pmol/l,
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p=0.23). Only LCHF+PW significantly decreased fasting insulin levels (−24.3±18.9 pmol/l, p=0.03). No changes were detected in the proinsulin:insulin ratio after any of the interventions (all p≥0.20). Conclusion: Four days of LCHF diet, with or without 15 minutes of walking after each meal, improves glucose control and lowers fasting proinsulin in patients with T2D. Further research is needed to determine if a LCHF diet can recover beta-cell function in T2D. 198 Vitamin D Status, Depression, Frailty and Sarcopenia in an ambulatory population with Diabetes Mellitus (DM) and Chronic Kidney Disease (CKD) STEPHANY ADAME PEREZ, LESLEY SETO, KAILASH JINDAL, PETER SENIOR, DIANA MAGER Edmonton, AB Background: Sarcopenia (SARC) is a condition highly prevalent in elderly adults with diabetes (DM) and chronic Kidney Disease (CKD). SARC and suboptimal vitamin D status has been associated with increased risk for morbidity and mortality and reduced quality of life. The study purpose was to describe the relationship between vitamin D status, frailty, depression and sarcopenia in an ambulatory population with DM and CKD. Methods: We prospectively studied body composition (Dual X-ray Absorptiometry), vitamin D status (serum 25-hydroxyvitamin D3 (25OHD3), frailty (Edmonton Frail Scale), depression (Major Depression Inventory: MDI) and QoL (SF-36) in adults with DM and CKD (69.9±7.3 years) over 3–5 years using validated methodologies. Results: Vitamin D status >75 nanomoles per litre (nmol/L) was associated with lower frailty scores (p<.05), but not MDI or SARC. DM duration and CKD stage were positively associated with the presence of sarcopenia (p<.05). There was a positive relationship between sarcopenia and frailty scores (p<.05), particularly when 25(OH)D3 concentrations are <75mol/L (p≤.01). Frailty scores were positively correlated with MDI scores (p<.01). There was a negative relationship between frailty and MDI scores with the physical component summary of SF-36 (p<.01). Conclusions: Patients with more advanced CKD and longer DM duration have a higher risk of sarcopenia. Increased frailty scores were associated with the presence of sarcopenia, suboptimal vitamin D status and reduced QoL. 199 Vitamin D Status in Indigenous Youth with Type 2 Diabetes MELISSA GABBS, ALLISON DART, FARRAH JABAR, KRISTINE KROEKER, TOM BLYDT-HANSEN, JON MCGAVOCK, BRANDY WICKLOW Winnipeg, MB Objective: Low vitamin D (25[OH]D) status is associated with an increased risk for several conditions including type 2 diabetes (T2D). The association between 25[OH]D sufficiency and T2D in youth is unknown. Research design and methods: A cross-sectional comparison of 25[OH]D status was performed among Indigenous youth with T2D (n=172) and overweight controls (n=53) within The Improving renal Complications in Adolescents with T2D through REsearch (iCARE) cohort. 25[OH]D status was classified as sufficient (≥50 nmol/L) or insufficient (<50 nmol/L). Univariate and multivariate logistic regressions were performed. Results: The cohort had a mean age of 15.4±2.6 at baseline, 65.3% were female, and 72.9% were from rural communities. The majority of youth (79.1%) presented with insufficient 25[OH]D. Age, sex, glycemic control, obesity, and rurality were not associated with 25[OH]D status. In multivariate models, youth with T2D were 55% less likely to be sufficient in 25[OH]D (OR 0.45 [95% CI: 0.21, 0.96]). Data collected in the summer months (OR 3.04 [95% CI: 1.33, 6.96])
Abstracts / Can J Diabetes 41 (2017) S22–S83
on dispersed human islets from healthy donors and donors with T2D. Results: mRNA analysis of glycine receptors α1 subunit reveal splice variation producing Glycine receptor α1 variant 1 and Glycine receptor α1 variant 3 (henceforth referred to as variant 1 and variant 3 respectively), where variant 1 is the full length protein while variant 3 contains a truncation on the N-terminus. Plasmids for both variant 1 and variant 3 were created and transfected into HEK cells. Variant 3 is unable to produce a current when stimulated with 300uM glycine. Molecular dynamic modeling of the receptor was employed to further study the structural differences between variant 1 and variant 3. Binding analysis demonstrated that glycine cannot bind to the binding site in variant 3. We suspect that variant 3 maybe upregulated in T2D and may explain the reduced glycine current associated with T2D and increased plasma glucose concentration. Conclusion: glycine receptor mediated current is known to be reduced in islets from human donors with T2D compared to human donors without T2D. Although insulin resistance is suspected to play a role in the reduced glycine current, our evidence suggests that upregulation of a non-functional receptor variant 3 may also contribute to reduced glycine current. 193 Gestational Diabetes Mellitus (GDM) Exposure and Postnatal Diet Influence Pancreatic Islet Function of the Rat Offspring TAYLOR MORRISEAU, NAVDEEP BRAR, PRASOON AGARWAL, MARIO FONSECA, STEPHANIE KERELIUK, LAURA COLEBO XIANG, NIVEDITA SESHADRI, KRISTIN HUNT, GRANT HATCH, CHRISTINE DOUCETTE, VERNON DOLINSKY Winnipeg, MB Introduction: As the obesity epidemic worsens, GDM rates are rapidly increasing. GDM exposure and obesity are strong risk factors for type 2 diabetes (T2D) development; however, the connections between GDM exposure, postnatal diet and islet dysfunction in offspring metabolic health remain unclear. Hypothesis: GDM exposure alters gene expression in islets and impairs beta cell function, which is worsened by a postnatal highfat and sucrose (HFS) diet. Methods: GDM was induced in female rats using a HFS diet, according to our established protocol. Litters of LEAN or GDM dams were divided and pups were weaned onto a low-fat (LF) or HFS diet. Pancreata and islets were isolated from 15-week-old offspring to analyze pancreas morphology, gene expression (RNA-seq), glucosestimulated insulin secretion (GSIS), and insulin content. Results: GDM exposure reduced GSIS by 15%, which was exacerbated by postnatal HFS exposure (85% GSIS reduction). Beta cell mass was reduced 2-fold from GDM exposed and HFS-fed offspring, compared to GDM-exposed LF-fed offspring. Islets from LF-fed GDM-exposed offspring exhibited 93 upregulated genes (including Il-6, Ppp1r3a, and Angptl4) and 30 downregulated genes. In the GDM-exposed HFS-diet group, a unique set of 510 genes (including Cel and Rbp4) were upregulated and 174 genes were downregulated. Conclusion: GDM exposure followed by postnatal over-nutrition additively impair islet function and induce greater changes in gene expression. Together, our findings suggest that GDM exposure and post-natal diet cumulatively interact to worsen metabolic health outcomes in offspring. 194 A Case of Hypertriglycideremia-induced Pancreatitis in Diabetic Ketoacidosis AURELIE PARE*, MICHAEL TSOUKAS Montreal, QC
Figure 1. Evolution of Triglyceride Level in Response to Insulin Therapy.
Clinical Presentation: An 54 year-old female known for poorly controlled diabetes mellitus type 2 presented to the emergency room for vomiting. She was found to have diabetic ketoacidosis (DKA) and hypertriglyceridemia. Computed tomography of the abdomen revealed grade D pancreatitis. Clinical Outcome: The patient’s pancreatitis was believed to be secondary to hypertriglyceridemia in the context of DKA. The patient was known for a similar episode having occurred one year prior. She improved following treatment of hypertriglyceridemia with intravenous insulin. Discussion: Hypertriglyceridemia causing acute pancreatitis is a known complication of DKA, having been previously reported in case reports and further examined in retrospective cohort studies of patients presenting with DKA. The pathophysiology, clinical presentation, and treatment of this condition are explored. Conclusion: Hypertriglyceridemia-induced pancreatitis associated with DKA is an uncommon entity that can present a diagnostic challenge for clinicians. 195 Identification of Novel Adipogenic Factors in the 14–3-3ζ Interactome During Adipocyte Differentiation YVES MUGABO, JASON T. LEE, NANCY N. FANG, AMPARO ACKER-PALMER, THIBAULT MAYOR, JAMES D. JOHNSON, GARETH E. LIM Repentigny, QC Adipogenesis involves a signaling network that requires strict temporal and spatial organization of effector molecules. We previously identified critical roles for the 14–3-3 protein family, and in particular 14–3-3ζ, as an essential upstream factor in adipocyte differentiation. 14–3-3ζ interact with diverse proteins to form its interactome suggesting that it can regulate several cellular processes that may be involved in adipogenesis. Thus, determining this interactome may help in further understanding the regulatory roles of 14–3-3ζ on adipocyte differentiation. Mouse embryonic fibroblasts from TAP-epitope-tagged 14–3-3ζ transgenic mice were generated, followed by an unbiased proteomic analysis to determine how adipocyte differentiation influences the 14–3-3ζ interactome. Interacting proteins were categorized using gene ontology and their role in adipogenesis, as assessed by Oil Red-O incorporation or quantitative PCR, were evaluated with a functional siRNA screen in 3T3-L1 cells. Proteomic analysis of the 14–3-3ζ interactome identified over 120 proteins that were unique to adipocyte differentiation. An enrichment of proteins related to RNA metabolism, processing, and splicing were found in the differentiation-associated interactome. Our screening approach revealed essential roles for RNA splicing-related proteins, Hnrnpf, Hnrnpk, Ddx6, and Sfpq in adipogenesis. This study demonstrates the ability of identifying novel adipogenic factors within the 14–3-3ζ interactome and reveals alternative path-
Abstracts / Can J Diabetes 41 (2017) S22–S83
ways and processes that may be facilitated by 14–3-3ζ during differentiation. Determining the interactome of 14–3-3 proteins may help in the discovery of novel therapeutic targets for obesity and type 2 diabetes treatments. 196 The Effect of Carbohydrate Restriction at Breakfast on Glycemic Control in Type 2 Diabetes. COURTNEY CHANG, MONIQUE FRANCOIS, JONATHAN LITTLE Kelowna, BC Purpose: To examine the effect of consuming a low-carbohydrate breakfast on postprandial and 24-hour blood glucose responses to mixed meals in individuals with type 2 diabetes (T2D). Methods: Adults with physician-diagnosed T2D (N=21, 60±10y, A1c: 6.7±0.7%, BMI: 31.6±7kg/m2) completed two 24-h isocaloric intervention periods, in a random order. Participants consumed either i) a low-carbohydrate breakfast (LC-BF; <10%CHO/85%FAT/15%PRO) or ii) a breakfast with dietary guidelines recommended nutrient profile (GL-BF; 55%CHO/ 30%FAT/ 15%PRO), with the same lunch and dinner provided (both 55%CHO/ 30%FAT/ 15%PRO). Continuous glucose monitoring was used to assess postprandial glucose responses to each meal (incremental area under the curve; iAUC) and the mean 24-h glucose during each intervention. Results: The postprandial glucose excursion (3 h iAUC) after the LC-BF was 80% lower than the GL-BF (p<0.01). Overall postprandial hyperglycemia, measured as the postmeal iAUC sum of breakfast, lunch and dinner, was significantly reduced with the LC-BF compared to the GL-BF (−69±104 mmol/L* 9 h, p=0.01). However, the mean 24-h blood glucose (LC-BF: 7.2±1 mmol/L vs GL-BF: 7.3±1.3 mmol/L, p=0.77) and glycemic variability were not significantly lower with the LC-BF (mean amplitude of glycemic excursions [MAGE]: LC-BF: 3.2±1.3 mmol/L vs GL-BF: 3.4±1.3 mmol/L). Conclusion: Restricting carbohydrate at breakfast reduces postprandial hyperglycemia in individuals with T2D. A low-carbohydrate breakfast may be a simple and effective strategy to reduce the development of diabetes complications in T2D and long-term interventions are warranted. 197 The Effect of a Short-term Low-carbohydrate Diet on Markers of Beta-cell Function in Type 2 Diabetes ÉTIENNE MYETTE-CÔTÉ, HELENA NEUDORF, CODY DURRER, JONATHAN P. LITTLE Kelowna, BC Aim: To determine if lowering glucose using a short-term lowcarbohydrate high-fat diet with (LCHF+PW) or without (LCHF) daily post-meal walks (PW) can improve markers of beta-cell dysfunction when compared to a low-fat dietary guidelines diet (DG) in individuals with type 2 diabetes. Methods: In a pilot study, 6 individuals with T2D (age: 67±7, HbA1c: 6.8±0.6, BMI: 31.8±2.7 means±SD) completed three isocaloric 4-day diet conditions in a randomized crossover design. The LCHF+PW diet included three daily 15-min post meal walks at a light-to-moderate intensity. Continuous glucose monitoring was used across all four days. Fasting blood samples taken before and after each intervention were used to analyze fasting proinsulin, insulin, and proinsulin:insulin ratio. Results: Compared to DG (7.5±0.9, 2.1±1.1 mmol/l), both LCHF (6.5±0.9, 1.1±0.4 mmol/l) and LCHF+PW (6.2±0.9, 1.0±0.4 mmol/l) decreased 4-day mean glucose concentrations (p≤0.001) and glycemic variability (p<0.05). The LCHF (−11.2±6.8 pmol/l) and LCHF+PW conditions (−17.1±11.9 pmol/l) decreased fasting proinsulin (both p≤0.02) whereas no change was observed after DG (−2.8±5.0 pmol/l,
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p=0.23). Only LCHF+PW significantly decreased fasting insulin levels (−24.3±18.9 pmol/l, p=0.03). No changes were detected in the proinsulin:insulin ratio after any of the interventions (all p≥0.20). Conclusion: Four days of LCHF diet, with or without 15 minutes of walking after each meal, improves glucose control and lowers fasting proinsulin in patients with T2D. Further research is needed to determine if a LCHF diet can recover beta-cell function in T2D. 198 Vitamin D Status, Depression, Frailty and Sarcopenia in an ambulatory population with Diabetes Mellitus (DM) and Chronic Kidney Disease (CKD) STEPHANY ADAME PEREZ, LESLEY SETO, KAILASH JINDAL, PETER SENIOR, DIANA MAGER Edmonton, AB Background: Sarcopenia (SARC) is a condition highly prevalent in elderly adults with diabetes (DM) and chronic Kidney Disease (CKD). SARC and suboptimal vitamin D status has been associated with increased risk for morbidity and mortality and reduced quality of life. The study purpose was to describe the relationship between vitamin D status, frailty, depression and sarcopenia in an ambulatory population with DM and CKD. Methods: We prospectively studied body composition (Dual X-ray Absorptiometry), vitamin D status (serum 25-hydroxyvitamin D3 (25OHD3), frailty (Edmonton Frail Scale), depression (Major Depression Inventory: MDI) and QoL (SF-36) in adults with DM and CKD (69.9±7.3 years) over 3–5 years using validated methodologies. Results: Vitamin D status >75 nanomoles per litre (nmol/L) was associated with lower frailty scores (p<.05), but not MDI or SARC. DM duration and CKD stage were positively associated with the presence of sarcopenia (p<.05). There was a positive relationship between sarcopenia and frailty scores (p<.05), particularly when 25(OH)D3 concentrations are <75mol/L (p≤.01). Frailty scores were positively correlated with MDI scores (p<.01). There was a negative relationship between frailty and MDI scores with the physical component summary of SF-36 (p<.01). Conclusions: Patients with more advanced CKD and longer DM duration have a higher risk of sarcopenia. Increased frailty scores were associated with the presence of sarcopenia, suboptimal vitamin D status and reduced QoL. 199 Vitamin D Status in Indigenous Youth with Type 2 Diabetes MELISSA GABBS, ALLISON DART, FARRAH JABAR, KRISTINE KROEKER, TOM BLYDT-HANSEN, JON MCGAVOCK, BRANDY WICKLOW Winnipeg, MB Objective: Low vitamin D (25[OH]D) status is associated with an increased risk for several conditions including type 2 diabetes (T2D). The association between 25[OH]D sufficiency and T2D in youth is unknown. Research design and methods: A cross-sectional comparison of 25[OH]D status was performed among Indigenous youth with T2D (n=172) and overweight controls (n=53) within The Improving renal Complications in Adolescents with T2D through REsearch (iCARE) cohort. 25[OH]D status was classified as sufficient (≥50 nmol/L) or insufficient (<50 nmol/L). Univariate and multivariate logistic regressions were performed. Results: The cohort had a mean age of 15.4±2.6 at baseline, 65.3% were female, and 72.9% were from rural communities. The majority of youth (79.1%) presented with insufficient 25[OH]D. Age, sex, glycemic control, obesity, and rurality were not associated with 25[OH]D status. In multivariate models, youth with T2D were 55% less likely to be sufficient in 25[OH]D (OR 0.45 [95% CI: 0.21, 0.96]). Data collected in the summer months (OR 3.04 [95% CI: 1.33, 6.96])