Abstracts – General
Cellular Senescence Compromises Stress Responses In Kidney Epithelial Cells
Siwei Chu [1], Kais Bietar [1], Stephanie Xie [1], Ursula Stochaj [1]
- Department of Physiology, McGill University
Protective Effects Of Hepatic Brca-1 Deletion In Diabetes-associated Liver Disease
Martha Ghebreselassie [1,2], Yoo Jin Park [1], Yu Zhe Li [1,3], Razq Hakem [4], MINNA WOO [1,2,3,5]
- Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada
- Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada
- Institute of Medical Sciences, University of Toronto, Toronto, ON, Canada
- Medical Biophysics, University of Toronto and Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada
- Division of Endocrinology and Metabolism, Department of Medicine, University Health Network and Sinai Health System, University of Toronto, Toronto, ON, Canada
Winter Is Coming: Intestinally-derived Proglucagon Mediate Nutrient Absorption And Gut Adaptation With Exposure To Cold
Antonio A. Hanson [1,2], Iryna Abramchuk [1,2], Natasha Trzaskalaski [1,2], Erin E. Mulvihill [1,2]
- University of Ottawa Heart Institute
Investigating The Metabolic Effects Of Pten In Parasympathetic Phox2b Neurons
Yu Zhe (Andy) Li [1,2], Joshua Rapps [1], Evan Pollock-Tahiri [1], Joe Eun Son [4], Chi-chung Hui [4] Minna Woo [1,2,3]
- Toronto General Hospital Research Institute, University Health Network
- Institute of Medical Science, University of Toronto
- Division of Endocrinology, Department of Medicine, University Health Network and University of Toronto
- The Hospital for Sick Children, Toronto, Canada
Acetylation As A Novel Post-translational Modification Of Mafa
Jiani Liang [1], Alberto Bartolome Herranz [1], Margot Chirikijian [2], Utpal B. Pajvani [1, 2]
- Department of Medicine, Columbia University Medical Center, New York, NY, USA
- Institute of Human Nutrition, Columbia University Medical Center, New York, NY, USA
Burning Fat And Preventing Plaque: Ketogenic Diet Intervention Improves Liver Fat And Atherosclerosis In Diet-induced Obese Mice
Cassandra Locatelli, My-Ahn Nguyen, Natasha Trzaskalski, Erin E Mulvihill
- University of Ottawa Heart Institute, Ottawa, Canada
- Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Canada
Effect Of Antipsychotics On Glucose Sensing By The Brain
Laura Castellani [1]*, Chantel Kowalchuk [1]*, Sandra Pereira [1,2]*, Raghunath Singh [1], Sally Wu [1], Roshanak Asgariroozbehani [1], Sri Mahavir Agarwal [1], Adria Giacca [2], Margaret Hahn[1]
(* co-first authors)
- Centre for Addiction and Mental Health, Toronto, ON
- Department of Physiology, University of Toronto, Toronto, ON
Liver-specific Depletion Of Dpp4
Natasha Trzaskalski [1,2], Branka Vulesevic [1], My- Anh Nguyen [1], Natasha Jeraj [1,2], Evgenia Fadzeyeva [1,2], Nadya Morrow [1,2], Antonio Hanson [1,2], Ilka Lorenzen-Schmidt [2], Erin E. Mulvihill [1,2]
- University of Ottawa Heart Institute
- The University of Ottawa
For Your Consideration: The(sugar)science
Insulin Receptor Expression In Peripheral Blood Mononuclear Cells As An Early Biomarker For Glucose Metabolism And Adiposity In Mother-child Dyads
Agustina Malpeli, María Victoria Fasano, Laura Orellano, Lucía Mazziota, Daniela Rocha, Lucrecia Fotia, Ignacio Méndez, Marisa Sala, Pablo Obregón, Andrea Tournier, Liliana Disalvo, Ana Varea, María Florencia Andreoli
- Instituto de Desarrollo e Investigaciones Pediátricas (IDIP)
- Hospital de Niños de La Plata – CIC-PBA. La Plata
A Novel, Virtual Inpatient Glucose Monitoring Service Highlights The High Rate Of Covid-19 Positivity In Hyperglycemic Patients
Anita O. Rich [1], Rita Eldridge [2], Rizvi, Ali A. [3]
- Diabetes Care and Education Specialist, Emory Johns Creek Hospital, Johns Creek, Georgia, USA
- Clinical Nutrition Manager, Emory Johns Creek Hospital, Johns Creek, Georgia, USA
- Professor of Medicine Endocrinology Metabolism and Lipids, The Emory Clinic, Johns Creek, Georgia, USA
Remission Of Type 2 Diabetes Following A Short-term Intervention With Insulin Glargine And Metformin/sitagliptin: A Randomized Controlled Trial
Natalia McInnes [1,2,3], Stephanie Hall [2], Irene Hramiak [4], Ronald J. Sigal [5], Ronald Goldenberg [6], Nikhil Gupta [6], Remi Rabasa-Lhoret [7], Manoela Braga [1], Vincent Woo [8], Farah Sultan [3], Rose Otto [1], Ada Smith [1], Diana Sherifali [9], Yan Yun Liu [2] and Hertzel C. Gerstein [1,2,3] on behalf of the REMIT-sita Collaborative Group
- Department of Medicine, McMaster University, Hamilton, Ontario, Canada
- Population Health Research Institute, Hamilton Health Sciences, Hamilton, Ontario Canada
- Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada
- Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada
- Departments of Medicine, Cardiac Sciences and Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
- LMC Diabetes and Endocrinology, Concord, Ontario, Canada
- Institut de Recherches Cliniques de Montréal, Université de Montréal, Montréal, Québec, Canada
- Department of Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada; 9 School of Nursing, McMaster University, Hamilton, Ontario, Canada
Diabetes In Patients Hospitalized With Covid-19 Infection; Characteristics And Therapeutic Approach
Glucagon Resistance At The Level Of Amino Acid Turnover In Obese Subjects With Hepatic Steatosis
Malte P. Suppli [1], Jonatan I. Bagger [1], Asger Lund [1], Mia Demant [1], Gerrit van Hall [2,3], Charlotte Strandberg [4], Merete J. Kønig [4], Kristoffer Rigbolt [5], Jill L. Langhoff [6], Nicolai J. Wewer Albrechtsen [2,7,8,9], Jens J. Holst [2,7], Tina Vilsbøll [1,10,11], Filip K. Knop [1,7,10,11]
- Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark
- Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
- Clinical Metabolomics Core Facility, Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
- Department of Radiology, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark
- Gubra ApS, Hørsholm, Denmark
- Department of Pathology, Herlev Hospital, University of Copenhagen, Herlev, Denmark
- Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
- Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
- Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
- Steno Diabetes Center Copenhagen, Gentofte, Denmark
Six-day S.c. Gip Infusion Increases Glycaemic Time In Range In Patients With Type 1 Diabetes
Sebastian M.N. Heimbürger [1,2,3], Bjørn Hoe [1,4], Chris N. Nielsen [1], Natasha C. Bergmann [1], Bolette Hartmann [3,5], Jens J. Holst [3,5], Joachim Størling [2,5], Tina Vilsbøll [1,2,4], Thomas F. Dejgaard [1,2], Mikkel B. Christensen [1,4,6], Filip K. Knop [1,2,3,4]
- Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark
- Steno Diabetes Center Copenhagen, Gentofte, Denmark
- Novo Nordisk Foundation Centre for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
- Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
- Department of Clinical Pharmacology, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark
Mitigation Of Glucocorticoid-induced Obesity In Mice Through Lxrβ Antagonism
Jia-Xu Li [1] and Carolyn L. Cummins [1,2]
- Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada
- Banting and Best Diabetes Centre, Toronto, ON, Canada
Inhibition Of The Nlrp3 Inflammasome Accelerates The Revascularization Of Transplanted Islets By Increasing Pdx-1-dependent Insulin Expression
Selina Wrublewsky [1], Thimoteus Speer [2], Lisa Nalbach [1], Mandy Pack [3], Beate M. Schmitt [1], Leticia P. Roma [4], Matthias W. Laschke [1], Michael D. Menger [1], Emmanuel Ampofo [1]
- Institute for Clinical and Experimental Surgery, Saarland University, 66424 Homburg, Germany
- Department of Internal Medicine IV, Nephrology and Hypertension, Saarland University, 66424 Homburg, Germany
- Medical Biochemistry and Molecular Biology, Saarland University, 66424 Homburg, Germany
- Biophysics Department, Center for Human and Molecular Biology, Saarland University, 66424 Homburg, Germany
The Nuclear Receptor Coregulator Arglu1 Potentiates Glucocorticoid-induced Diabetes
Florian Le Billan[1], Lilia Magomedova [1], Michael F. Saikali [1], Judy Deng [1], Carolyn L. Cummins [1,2]
- Department of Pharmaceutical Sciences, University of Toronto, Toronto, ON, Canada
- Banting and Best Diabetes Centre, Toronto, ON, Canada
Single-cell Rna Sequencing Reveals A Role For Ros Signaling In Nutrient-induced S-cell Proliferation
Alexis Vivoli [1,2], Julien Ghislain [2], Anne-Laure Castell [1,2], Ali Filali [2], Robert M. Sladek [3], Vincent Poitout [1,2]
- Department of medicine, University of Montreal
- CHUM research Center
- McGill University and Quebec Genome Center
Investigation Of Cell Expansion During Beta-like Cell Differentiation Of Human Embryonic Stem Cells
Amanda Oakie [1] and Maria Cristina Nostro [1,2]
- McEwen Stem Cell Institute, University Health Network, Toronto, Ontario, M5G 1L7, Canada
- Department of Physiology, University of Toronto, Toronto, Ontario, M5S 1A8, Canada
Elevating Proinsulin Levels By Deletion Of Pcsk1 And Pcsk2 In Beta Cells Results In Islet Adaptation And Mild Hyperglycemia In Mice
Austin J. Taylor [1], Yi-Chun Chen [1], Daniel Pasula [1], Dan S. Luciani [1], C. Bruce Verchere [1]
- Department of Pathology and Laboratory Medicine Department of Surgery University of British Columbia BC Children’s Hospital Research Institute
C-peptide Suppression Relates To Changes In Glycemia But Not Glucose Disposal In Hyperinsulinemic Euglycemic Clamp
Jan Gojda [1], Marek Å tÄpán [1, 2], Eva Krauzová [1, 2], Michaela Åiklová [1, 2]
- Institute of pathophysiology, Third Faculty of Medicine, Charles University, Prague, Czech Rep.
- Dept. of Medicine, University Hospital Kráľovská© Vinohrady and Third Faculty of Medicine, Charles University, Prague, Czech Rep.
C-peptide Distribution And Associated Clinical Factors In Longstanding Type 1 Diabetes: Analysis Of The Canadian Study Of Longevity In Type 1 Diabetes
Sebastien O. Lanctôt [1]*, Leif Erik Lovblom [1]*, Michelle Morris [1], Nancy Cardinez [1], Daniel Scarr [1], Evan Lewis [1], Julie A. Lovshin [2], Yuliya Lytvyn [3], Geneviève Boulet [1], Alexandra Bussières [4], Michael H. Brent [5], Narinder Paul [6], Vera Bril [7], David Z. I. Cherney [1,8,9], and Bruce A. Perkins [1,10]
- Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital. Toronto, Ontario, Canada.
- Division of Endocrinology and Metabolism, Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
- Department of Medicine, Division of Nephrology, University of Toronto, Toronto, Ontario, Canada.
- Faculty of Medicine and Health Sciences, University of Sherbrooke, Sherbrooke, Québec, Canada
- Department of Ophthalmology and Vision Sciences Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
- Joint Department of Medical Imaging, University of Toronto, Toronto, Canada and Department of Medical Imaging, Western University, London, Ontario, Canada.
- Department of Medicine, Division of Neurology, University Health Network, University of Toronto, Toronto, Ontario, Canada.
- Department of Physiology, University of Toronto, Toronto, Ontario, Canada.
- Department of Physiology and Banting and Best Diabetes Centre, University of Toronto, Toronto, Ontario, Canada.
- Department of Medicine, Division of Endocrinology and Metabolism, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada.
The Transcription Factor Tcf7 Is Not Essential For βeta-cell Function And Glucose Homeostasis
Kiran Deep Kaur, Chi Kin Wong, Laurie L Baggio, Jacqueline L. Beaudry, Brandon L. Panaro, Dianne Matthews, Xiemin Cao, and Daniel J. Drucker
Changes In The Lipidome In Type 1 Diabetes Following Low Carbohydrate Diet: A Randomized Crossover Trial
Naba Al-Sari [1], Signe Schmidt [1,2,3], Tommi Suvitaival [1], Min Kim [1], Kajetan Trošt 1#, Ajenthen G. Ranjan [1,2,3], Merete B. Christensen [1,3], Anne Julie Overgaard [1], Flemming Pociot [1,4], Kirsten Nørgaard [1,3]*, Cristina Legido-Quigley [1,5]*
- Steno Diabetes Center Copenhagen, Denmark
- Danish Diabetes Academy, Denmark
- Dept. of Endocrinology, Copenhagen University Hospital Hvidovre, Denmark
- Dept. of Clinical Medicine, University of Copenhagen, Denmark
- Institute of Pharmaceutical Science, King’s College London, UK
#Current address: Novo Nordisk foundation Center for Basic Metabolic Research, Denmark
Innovative Technology For "cold Chain" Protects Insulin Against Thermal Damage
Paul Zimmet, Merlin Thomas, Mark Cooper, Keith Al-Hasani, Carlos Rosado, and Pravansu Mohanty
Modelling Of Electrical Fingerprints Reveals Transcriptomic Profiles Linked To Alpha Cell Dysfunction In Type Two Diabetes
Theodore dos Santos [1], Linford Briant [2], XiaoQing Dai [1], Joan Camunas-Soler [3], Austin Bautista [1], Patrik Rorsman [3], Patrick E. MacDonald [1]
- Alberta Diabetes Institute, University of Alberta, Edmonton, AB, Canada
- Oxford Centre for Diabetes Endocrinology and Metabolism, University of Oxford, OXON, United Kingdom
- Stanford University School of Medicine, Stanford, CA, United States of America
The Role Of Growth Differentiation Factor 15 In Patients With Acute Coronary Syndrome And Type 2 Diabetes Mellitus
Iryna Vyshnevska [1], Olga Petyunina [1], Mykola Kopytsya [1]
- GI “L.T. Malaya therapy national institution of NAMSU”
Diabetes mellitus in patients with the acute coronary syndrome (ACS) is an independent risk factor for death, the frequency of which is two times higher than the mortality rate of ACS without diabetes.
Purpose: to estimate the prognostic role of GDF-15 in patients with ACS and T2DM. Materials and methods. The study involved 140 patients with ACS. The average age was (61.8 + 1.3) years.
The examined patients had T2DM in 15.7% of cases. The levels of GDF- 15 were determined during the first day after ACS. The endpoint was all-cause mortality. During 6-months follow up 11% of patients died.
Results. Patients from the group with T2DM were more likely to have a family history of coronary heart disease (p < 0.05) as well as a previous myocardial infarction (p < 0.05). An assessment revealed significant differences in the levels of GDF-15 (p < 0,01) in both groups. The association between GDF-15 and T2DM was found. A ROC analysis determined that at the value of GDF-15 ≥ 3894 pg/ml was (p < 0.05) associated with the presence of T2DM (sensitivity-64%, specificity-75%; AUC 0.68).
Conclusions. An association between GDF-15 and high risk of ACS complications in patients with concomitant T2DM has been identified.
Hepatic Deletion Of Foxo1 Signaling Rescues The Metabolic Deficits Caused By Mtorc2 Inhibition
Reji Babygirija [1,2,3], Michaela Murphy [1,2], Shelly Shonsella [1,2], Sabrina Dumas [1,2], Victoria Flores [1,2], Cara Green [1,2], Heidi Pak [1,2] and Dudley W. Lamming [1,2,3]
- Department of Medicine, University of Wisconsin-Madison,
- William S. Middleton Memorial Veterans Hospital,
- Department of Nutritional Sciences, University of Wisconsin-Madison, Madison WI, and Graduate Program in Cellular and Molecular Biology, University of Wisconsin-Madison, Madison, WI, USA
Our previous studies have demonstrated that impaired glucose homeostasis, which is notably one of the most severe negative effects of chronic administration of rapamycin results from the inhibition of mTOR complex 2 while its beneficial effects on aging is mediated via mTORC1 inhibition.
One major question that needs to be answered is how can we block the side effects of rapamycin? Forkhead boxO (FOXO) transcription factors,Foxo1 can be the primary effector of many of the metabolic phenotypes observed either in mice lacking hepatic Rictor or as a result of treatment with rapamycin and therefore we hypothesized that genetic depletion of Foxo1 can have a protective effect in rescuing the metabolic defects caused by mTORC2 inhibition.
We compared the metabolic health of both male and female mice in which we have deleted hepatic Rictor, Foxo 1 and both Foxo1 and Rictor, as well as wild-type littermates. Inhibiting Foxo1 signaling rescued the impaired glucose tolerance caused by deletion of rictor, with a stronger effect seen in males than females.
These preliminary results suggests that blocking Foxo1 signaling can rescue metabolic effects caused by mTORC2 inhibition.
Metabolic Endotoxemia Is Dictated By The Type Of Lipopolysaccharide
Fernando F. Anhê [1,2,3], Nicole G. Barra [1,2,3], Joseph F. Cavallari [1,2,3], Brandyn D. Henriksbo [1,2,3] Jonathan D. Schertzer [1,2,3]
- Department of Biochemistry and Biomedical Sciences, McMaster University, 1200 Main St. W., Hamilton, Ontario, Canada L8N 3Z5
- Farncombe Family Digestive Health Research Institute, McMaster University, 1200 Main St. W., Hamilton, Ontario, Canada L8N 3Z5
- Centre for Metabolism, Obesity and Diabetes Research, McMaster University, 1200 Main St. W., Hamilton, Ontario, Canada L8N 3Z5
Lipopolysaccharides (LPS) can promote inflammatory and detrimental metabolic endotoxemia
1. LPS from different bacteria can be strong or weak triggers, or antagonists of inflammation, but still contribute to Endotoxin Units (EU)
2. Research Design and Methods: Lean/obese mice were acutely/chronically treated with different LPS followed by glucose and insulin tolerance test, glucose-stimulated insulin/incretin secretion test and gut permeability assessment.
Results: We found that Escherichia coli LPS impaired gut barrier function and worsened glycemic control in mice, whereas equal doses of LPS from other bacteria did not (Fig 1). Matching the LPS dose from R. sphaeroides and E. coli by EU revealed that only E. coli LPS promoted dysglycemia, adipose inflammation, and augmented insulin and GLP-1 secretion (Fig 2). Metabolically beneficial endotoxemia from R. sphaeroides LPS counteracted dysglycemia caused by E. coli LPS and promoted insulin sensitivity in obese mice (Fig 3). Deacylation was sufficient to transform E. coli LPS-driven endotoxemia into metabolically beneficial endotoxemia (Fig 4).
Discussion: The concept of metabolic endotoxemia should be expanded beyond LPS load to include LPS characteristics, where the balance of deleterious and beneficial endotoxemia regulates gut barrier function, inflammation, hormones and blood glucose.
Regulation Of Glucose Metabolism Via The Intra-islet Dpp4/incretin Axis
Evgenia Fadzeyeva [1,2], Branka Vulecevic [1,2], Natasha Trzaskalski [1,2], Erin E. Mulvihill [1,2]
- University of Ottawa Faculty of Medicine, Ottawa, ON, Canada
- University of Ottawa Heart Institute, Ottawa, ON, Canada
Postprandial glycemic control can be achieved through the signalling by the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). Signalling through the incretin receptors potentiates glucose-stimulated insulin secretion and decreases glucagon secretion. The incretin hormones have been traditionally characterized to be secreted by distinct gut enteroendocrine cells in response to nutrients; however, recent studies have demonstrated that pancreas-, and not gut-derived GLP-1 may be required for proper glucose homeostasis. Both incretins are rapidly inactivated by a widely expressed serine protease dipeptidyl peptidase-4 (DPP4). Dpp4 mRNA and protein are also present in isolated mouse islets.
Therefore, we assessed whether islet β-cell-derived DPP4 is an important target for glucoregulation. Treatment of Glp1r/Giprβ-cell-/- mice with the DPP4i demonstrated that β-cell incretin receptor signaling is required to mediate these drugs’ beneficial effects on glucose homeostasis. We showed that both DPP4i-treated wildtype and untreated Dpp4β-cell-/- islets exhibit increased glucose-stimulated insulin secretion during perifusion after a high-fat diet feeding. Eliminating Dpp4 from β-cells improved oral glucose tolerance and insulin sensitivity in female mice without affecting circulating DPP4 or incretin levels.
Finally, pancreas- or β-cell-specific Dpp4 elimination did not improve glucose tolerance, insulin tolerance, or insulin secretion in chow- or high-fat diet-fed male mice.
Individualized Insulin Regimens And Cgm Use With Close Follow-up In Ambulatory Diabetes Management
Celeste Eberlein, MSN, RN, NPD-BC Ali Rizvi, MD [1,2]
- Emory Clinic Endocrinology-Johns Creek
- Emory Healthcare, Atlanta, Georgia
Despite advancements in pharmacologic therapies, achieving glucose targets in people with diabetes often remains a challenge. We reviewed the records of patients managed in an academic endocrinology practice referred for suboptimal glucose control.
Over an 8-month period, 99 patients (33 females and 66 males, average age 61 years) were treated with insulin and started on personal continuous glucose monitoring (pCGM). Of these, 43 patients were evaluated after a recent hospital stay associated with significant hyperglycemia, ketoacidosis, or acute COVID-related illness.
The outpatient insulin regimen, with or without other medications, was adjusted every 2-4 weeks via in-person and telehealth visits, and remote data upload. 27 patients were on basal insulin only, while 72 were on multiple daily injections or insulin pumps. The average A1c was 9.4% at initial visit and 7.1% at a mean follow-up of 6 months, a decrease of 2.3% (p< 0.05). The average time-in-range increased from 63% at first pCGM download, to 69% at 3 months (p=0.05).
In summary, in patients with suboptimal ambulatory glucose control or recent hospital stay with significant hyperglycemia or new-onset diabetes, frequent and tailored insulin therapy adjustments with pCGM use and close ambulatory follow-up can lead to improved glycemic control.
A Type 1 Diabetes Genetic Risk Score Predicts Insulin Deficiency In Patients With Obesity
Shohinee Sarma [1] and Satya Dash [2, 3]
- Division of Endocrinology and Metabolism, University of Toronto, Toronto, ON, Canada
- Department of Medicine, University Health Network and University of Toronto, Toronto, Ontario, Canada
- Banting and Best Diabetes Centre, University of Toronto, Toronto, Ontario, Canada
Introduction: There is evidence that genetic risk scores (GRS) can help differentiate between Type 1 (T1D) and Type 2 diabetes (T2D). [1]
With increasing rates of obesity, differentiating between diabetes subtypes becomes challenging. Diagnostic tests of discrimination have limitations. Previous data show that a T1D GRS is highly discriminative of progression to insulin deficiency.
Methods: We used a T1D GRS to predict insulin deficiency in 286 patients with obesity referred for weight loss to the University Health Network (UHN) bariatric program. We used associated genetic variants for T1D from published studies. [2]
Ten genetic variants were identified using genetic microarray sequencing. Odds ratios (OR) for single nucleotide polymorphisms (SNPs) were obtained from available studies. [3]
The T1D GRS was created by taking the weighted sum of risk alleles across each SNP multiplied by the log OR for each allele. An independent two-sample t-test assessed mean GRS between patients ever on insulin and never on insulin. Results: Our preliminary results showed that GRS is predictive of differentiating insulin deficiency with statistical significance (p-value=0.5).
Discussion: Next steps include creating a risk prediction model using T1D GRS alongside biochemical and clinical parameters to assess progression of insulin deficiency in patients with obesity. [4]
Jubile Cohort: One Century After Insulin Discovery, 50 Years Of Insulin Therapy
Jean-Jacques Altman, Ralph Niarra, Beverley Balkau, Christophe Vincent-Cass for the Jubile Study Group Hôpital Européen Georges Pompidou et Université Paris V, France
Quality of life might become the most challenging long‐term complication of chronic diseases.The JUBILE study describes quality of life of people with type 1 diabetes for about 50 years or more.
Delphi method validated patients and physicians questionnaires:1200 were circulated, 808 returned. Age at diagnosis was 15 ± 10 years, the duration of type 1 diabetes 49 ± 6 years, HbA1c 7.4 ± 0.9% and 52% were men. Macrovascular disease was present in 32%, 46% had no or mild non proliferative retinopathy. Insulin pumps were used by 25%. Blood glucose was monitored at least 5 times daily by 67% of patients. Men had 1.8 ± 1.2 children, women 1.4 ± 1.0. More than half (55%) of this population was working, 38% had a university degree.
Patients still had a busy life, going out (59%), eating out (82%), playing sports (38%) and travelling (66%). No differences appeared based on age, duration of diabetes, social features or demography. Fifty years of type 1 does not prevent people from having a high quality of life, a long happy family life, having children, highly qualified job, travelling abroad: a message of hope that is comforting for patients, their family, relatives and the medical teams.
Prolactin Mediates Ffa2 Expression And Affects Beta Cell Function During Pregnancy
Kai Xu [1], Barton Wicksteed [1], Medha Priyadarshini [1], Guadalupe Navarro [1,2], Brian T Layden [1]
- Department of Medicine, Division of Endocrinology, Diabetes, and Metabolism, University of Illinois at Chicago, Chicago, Illinois
- Takeda, Medical Science Liaison Immunology – Rare Diseases, Lexington, Massachusetts, United States
Gestational diabetes leads to increased complications for both the mother and offspring1. One factor contributing to risks of gestational diabetes is the gut microbiome, which undergoes dramatic alteration during pregnancy2.
However, the mechanism by which the gut microbiome impacts gestational diabetes is unclear. Our data suggest a link between the gut microbiome and insulin secretion, specifically via FFA2, a short- chain fatty acids (SCFAs) receptor that can be activated by SCFAs. Previous data from us shows that FFA2 expression peaks at gestation day 15 (G15) within islets3.
Furthermore, intraperitoneal glucose tolerance tests (IPGTT) at G15 in a FFA2 global knockout model reveal impaired glucose tolerance due to reduced insulin secretion. Here, we test the relationship between FFA2 and beta cell function using our female beta cell FFA2 knockout mouse model. In this model, we observed impaired IPGTT at G15. Additionally, CD1 islets incubated with prolactin (0, 200, 1000 ng/ml) for 24 hours showed a dose-dependent increase in FFA2 RNA expression
These results show that prolactin regulates FFA2 expression, and thus likely affects beta cell function during pregnancy.
Development Of Sex-specific Models To Predict Insulin Sensitivity And Secretion Measured By The Botnia Clamp
Beaudry, M [1], Bissonnette, S [1], Lamantia, V [1], Devaux, M [1], Faraj, M [1]
- Faculty of Medicine, Université de Montréal; Institut de recherches cliniques de Montréal (IRCM), and Montréal Diabetes Research Center (MDRC), Montréal, QC
Introduction: There are sex-differences in insulin secretion (ISc) and sensitivity (IS) in humans(1,2); however, current fasting indexes used to predict these variables, such as HOMA and QUICKI, are not sex-specific.
We aimed to develop sex-specific prediction models for ISc and IS, measured by the gold-standard Botnia clamp, using clinical parameters.
Methods: Post-hoc analysis was conducted on pooled baseline data of two trials(2,3,4) (39 men:66 postmenopausal women, 45-73 years, BMI=20-51 kg/m2, without metabolic chronic disease or medication).
We assessed ISc by a 1-hour intravenous glucose tolerance test followed by IS by a 3-hour hyperinsulinemic-euglycemic clamp(1,2). Regression analysis was used to predict ISc and IS using BMI, waist and hip circumference, and fasting plasma glucose, insulin, and lipid-related parameters as independent variables.
Results: In women, ISc was predicted by insulin, glucose, apoB and free fatty acids (R2: model=0.69 vs HOMA-β=0.53), and IS by insulin, waist circumference and cholesterol (R2: model=0.64 vs HOMA-IR= 0.40 or QUICKI=0.53).
In men, ISc was predicted by insulin, glucose and BMI (R2: model=0.82 vs HOMA-β=0.69) and IS by waist circumference, glucose, insulin and triglycerides (R2: model=0.71 vs HOMA-IR=0.38 or QUICKI=0.56).
Discussion: The developed models predict ISc and IS in non-diabetic men and post-menopausal women better than current indexes.
Mdi Vs Insulin Pump
Naba Al-Sari [1], Signe Schmidt [1,2,3], Tommi Suvitaival [1], Min Kim [1], Kajetan Trošt 1#, Ajenthen G. Ranjan [1,2,3], Merete B. Christensen [1,3], Anne Julie Overgaard [1], Flemming Pociot Suman Fathima