bluuebunny/crossref_metadata_2025 huggingface dataset:
268-OR: Impact of the COVID-Pandemic on Antihyperglycemic Prescription Patterns in Canada
Authors: CHENG ALICE Y. , GOLDENBERG RONALD , KRAWCHENKO IRIS E. , TYTUS RICHARD , HAHN JINA , LIU AIDEN R. , LAN TOMMY , MILLSON BRADLEY , HARRIS STEWART B.
Published: May 2022

Background: COVID-public health measures may have impacted diabetes care through delayed care and reduced medication access. This study describes antihyperglycemic medication prescription patterns among adults with type 2 diabetes (T2D) before and during the COVID-pandemic in Canada.

Methods: Using IQVIA’s longitudinal pharmacy based prescription data, antihyperglycemic prescriptions from March 1, 2018 to February 28, 2021 were analyzed among adults who had ≥1 prescription for a non-insulin antihyperglycemic drug. The number of people who: 1) had antihyperglycemic prescriptions,2) were newly started on antihyperglycemic drugs, and3) were newly diagnosed with T2D (inferred from prescriptions) were reported.

Results: The number of people who had ≥1 antihyperglycemic prescription was comparable in the year of the COVID-pandemic (March 2020 to February 2021) and the year prior (March 20to February 2020) . The number of people who newly initiated a GLP-1RA, SGLT2i or second-generation basal insulin analogue decreased for the first few months of the pandemic (April to September 2020) with recovery thereafter. The number of people who were newly diagnosed with T2D decreased by 7% in the COVID-year.

Conclusion: Fewer people initiated newer antihyperglycemic medications and fewer people were newly diagnosed with T2D in the first few months for the pandemic which may reflect reduced health care access.

Disclosure

A.Y.Cheng: Advisory Panel; Abbott, AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Dexcom, Inc., Eli Lilly and Company, HLS Theraoeutics, Insulet Corporation, Janssen Pharmaceuticals, Inc., Medtronic, Novo Nordisk, Sanofi, Board Member; Type 1 Diabetes Think Tank Network, Other Relationship; Diabetes Canada, Speaker's Bureau; Bausch Health, Canada, Merck & Co., Inc. R.Goldenberg: Consultant; IQVIA Inc., Speaker's Bureau; Amgen Canada, AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk Canada Inc., Sanofi. I.E.Krawchenko: Speaker's Bureau; Janssen Pharmaceuticals, Inc. R.Tytus: Other Relationship; Banty , Boehringer Ingelheim International GmbH, Canadian Health Research Company, Merck & Co., Inc., Novo Nordisk, Pfizer Inc. J.Hahn: Employee; Novo Nordisk Canada Inc. A.R.Liu: Employee; Novo Nordisk A/S, Novo Nordisk Canada Inc. T.Lan: Other Relationship; Novo Nordisk Canada Inc. B.Millson: Other Relationship; Novo Nordisk Canada Inc. S.B.Harris: Consultant; Abbott, AstraZeneca, Eli Lilly and Company, Novo Nordisk, Sanofi, Other Relationship; Abbott, AstraZeneca, Bayer Inc., Dexcom, Eli Lilly and Company, HLS Therapeutics, Janssen Pharmaceuticals, Inc., Novo Nordisk, Sanofi, Research Support; Applied Therapeutics Inc., AstraZeneca, Canadian Institutes of Health Research, Juvenile Diabetes Research Foundation (JDRF) , Novo Nordisk, Sanofi, The Lawson Foundation.
269-OR: No BMI Increase during the COVID-Pandemic in Children and Adults with T1D in Three Continents: Joint Analysis of ADDN, T1DX, and DPV Registries
Authors: NARAYAN KRUTHIKA , AUZANNEAU MARIE , NOOR NUDRAT , ROMPICHERLA SAKETH , EBEKOZIEN OSAGIE , GLASTRAS SARAH , SMART CARMEL E. , BACHMANN SARA , WELP REINHARD , MAAHS DAVID M. , HOLL REINHARD W. , CRAIG MARIA E.
Published: May 2022

The COVID-pandemic necessitated worldwide lockdowns in 2020, with restrictions on physical activity and changes in eating habits. We investigated temporal trends in BMI in three international T1D registries between 2018-2020. Data were extracted from DPV (Germany/Austria/Luxembourg/Switzerland) , T1D Exchange (T1DX, US) , and Australasian Diabetes Data Network (ADDN) . The period affected by the COVID-pandemic was defined as Mar to Dec 2020 and compared with the 9-mth periods in 2018 and 2019. Median age and median BMI were aggregated for each individual per year. Mean BMI was aggregated by year, sex, and age groups (stratified by 2 yearly intervals to age 20 years, and yearly until age 60. Study population: ADDN (n=29,875, mean age 21.9 years, 51% male) ; DPV (n=118,580, 21.2 years, 53% male) ; T1DX (n=47,122, 21.3 years, 51% male) . BMI stratified by age group and sex are shown in the figure. There were no apparent BMI differences across the three years. Females aged 30-40 years and 40-50 years in ADDN only demonstrated a slightly higher BMI in 2020. Conclusion: At a population level, mean BMI was not different before and during the pandemic in people with T1D. In some individuals, a healthier lifestyle or more regulated nutritional intake may have counteracted potential adipogenic effects of lockdown measures.

Disclosure

K.Narayan: None. D.M.Maahs: Advisory Panel; Abbott Diabetes, Eli Lilly and Company, Medtronic, Novo Nordisk, Sanofi, Consultant; Aditx Therapeutics, Inc., Biospex. R.W.Holl: None. M.E.Craig: None. M.Auzanneau: None. N.Noor: None. S.Rompicherla: None. O.Ebekozien: None. S.Glastras: None. C.E.Smart: None. S.Bachmann: None. R.Welp: None.
27-LB: Prevalence and Severity of Diabetic Retinopathy in African Americans with End-Stage Kidney Disease
Authors: EGEOLU MICHELLE , MANISHIMWE EXAUCEE , ZABALA ZOHYRA E. , MOAZZAMI BOBAK , CALEON RAMONCITO L. , GALINDO RODOLFO J. , NAVARRETE JOSE E. , GERGES AMANY Y.G. , PENG LIMIN , UMPIERREZ GUILLERMO E.
Published: May 2022

Background and Methods: This cross-sectional study determined the prevalence of diabetic retinopathy (DR) in non-Hispanic African Americans (AA) with end-stage-kidney disease (ESKD) and their impact on quality of life. A total of 95 adults with type 1 (n= 10) and type 2 (n= 85) on dialysis diabetes were assessed for DR using portable hand-held (Optomed Aurora) with artificial intelligence report with AEYE Diagnostic System (AEYE-DS) , visual acuity using a Snellen chart, and social determents of health, and standardized questionnaires (Kidney Disease Quality of Life (KDQoL) , depression screening (Patient health Questionaire-9) and food insecurity.

Results: Among the 95 participants (female 51%, mean age 59.5 ±12.3 years, duration of diabetes (DM) 18.2 ± 12.0 years and duration of dialysis 4.5±3.6 years) . A total of 55% of patients had a diagnosis of (DR+) , who had a longer duration of DM (18.8±9.5 vs. 15.8±12.2 years, p=0.20 and shorter duration of dialysis (3.6±2.7 vs. 5.9±5.0 years compared to DR negative (DR-) , p=0.09. Kidney Disease Quality of Life score on symptoms/problems related to ESKD and greater effect of kidney disease in daily life were lower compared to the general US, AA population with ESKD, p <.0001) . DR+ had worse physical health (p: 0.09) , greater rate of severe vision impact on quality of life (p= 0.01) , similar rates below the federal poverty level per household income (25% vs. 30%) , non-statistically significantly higher Ph-Q9 depression (6.9±5.3 vs. 4.8±4.1, p=0.16) , and food insecurity scores compared to without DR (1.07±1.51 vs. 0.83±1.56, p=0.33) . Overall, the prevalence of diabetic retinopathy was 55% based on the AEYE artificial intelligence system. Diabetic retinopathy was associated with poor quality of life and physical health, higher rates of poverty, and greater impact of vision impairment on quality of life compared to DR negative. Our preliminary finding highlights the increased disease burden of DR in AAs with ESKD, indicating an alarming gap in care.

Disclosure

M. Egeolu: None. G. E. Umpierrez: Research Support; AstraZeneca, Dexcom, Inc., Novo Nordisk. E. Manishimwe: None. Z. E. Zabala: None. B. Moazzami: None. R. L. Caleon: None. R. J. Galindo: Advisory Panel; Sanofi, WW International, Inc., Research Support; Dexcom, Inc., Eli Lilly and Company, Novo Nordisk. J. E. Navarrete: None. A. Y. G. Gerges: None. L. Peng: None.
27-OR: Fatty Acid Uptake and Metabolism in Human Adipose Tissue Is Decreased upon Consuming an Isocaloric High–Saturated Fat Diet and Partially Genetically Determined
Authors: KRUSE MICHAEL , OST ANNE-CATHRIN , HORNEMANN SILKE , HOFFMANN DANIELA , FRAHNOW TURID , BUSJAHN ANDREAS , PFEIFFER ANDREAS F.
Published: May 2022

CD36 transports fatty acids (FA) into adipocytes and is increased in white adipose tissue (WAT) in obesity. In rodents, however, it was shown that CD36 knock out is protective for diet induced adiposity. In humans a hypocaloric high fat diet decreased CD36 gene expression in WAT. This study investigated the response of gene expression of FA uptake and metabolism in sub cutaneous WAT after a sudden switch from a healthy isocaloric low fat diet to an isocaloric high fat diet (HF) in healthy human twins. 35 monzyogotic and dizygotic healthy pairs of twins (women and men, age 18 - 70) were investigated for 12 weeks. An isocaloric diet rich in carbohydrates (55% carbohydrates, 30% fat, 15% protein, LF) was applied for 6 weeks, followed by an isocaloric diet rich in saturated fat (40% carbohydrates, 45% fat, 15% protein, HF) for another 6 weeks. Body weight (BW) , BMI, serum FA and gene expression of CD36, PDK4, PGC1α and CPT1α by qPCR were analyzed after the LF period, after one week (HF1) and at the end (HF6) of the HF period. BW did not change during the study. Serum FA were unchanged at HF1 but decreased at HF6 by 18% (P<0.compared to LF) . Gene expression of CD 36 was strongly decreased by 33% at HF1 and by 26% at HF6, respectively, compared to LF (both P<0.001) . A significant decrease of gene expression of PDK4 by 18% was observed at HF1 and by 27% at HF6 (both P<0.0compared to LF) . Gene expression of PGC1α and CPT1α were not changed at HF1 but decreased both at HF6 by 14% (both P<0.0compared to LF) and were highly heritable: 64% for PGC1α and 48% for CPT1α. Gene expression was positively correlated with BMI for CD36 at HF1 and for PDK4 at LF, HF1 and HF6 (P<0.05) . These data indicate that gene expression of transport (CD36) and re-esterification (PDK4) of FA are not only dependant on the amount of nutritional fat, but also on energy content. Moreover, expression of genes controlling mitochondrial (PGC1α) and FA (CPT1α) metabolism appear to be genetically determined.

Disclosure

M.Kruse: None. A.Ost: None. S.Hornemann: None. D.Hoffmann: None. T.Frahnow: None. A.Busjahn: None. A.F.Pfeiffer: None.

Funding

German Federal Ministry of Education and Research (0315424)
276-OR: Impaired Glucagon-Mediated Suppression of VLDL-TG Secretion in Individuals with MAFLD
Authors: HEEBØLL SARA , RISIKESAN JEYANTHINI R. , GRONBAEK HENNING , SØNDERGAARD ESBEN , NIELSEN SØREN
Published: May 2022

Background: Individuals with Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD) have both elevated triglyceride and glucagon levels, although glucagon suppresses the very-low-density lipoprotein-triglyceride (VLDL-TG) secretion in lean individuals. Therefore, we hypothesized that the glucagon-mediated suppression of VLDL-TG secretion is impaired in MAFLD, with greater impairment in individuals with steatohepatitis (MASH) than individuals with simple steatosis (MAFL) .

Methods: 28 participants were included in the study (seven overweight control subjects (CON) , patients with MAFL, and with MASH) . We performed a somatostatin-clamp with replacement doses of growth hormone, insulin (0.2 mU/kg/min) and glucagon to suppress endogenous hormone production. Participants were studied during low-dose glucagon infusion (0.65 ng/kg/min, t=0─270 min, LowG) followed by a high-dose glucagon infusion (1.5 ng/kg/min, t=270─450 min, HighG) . We used 14C-labeled VLDL-TG and 3H-labeled glucose tracers to evaluate VLDL-TG secretion and endogenous glucose production (EGP) .

Results: HighG suppressed VLDL-TG secretion compared to LowG in all groups, but with a greater reduction in VLDL-TG secretion in CON than in the MAFLD groups (CON 36% (±SD 19%) ; MAFL 10% (±SD 8%) ; MASH 13% (±SD 16%) , p<0.01) . Thus, the suppression was similarly mitigated in both MAFLD groups. This led to insignificant reductions in plasma VLDL-TG, TG and VLDL-TG oxidation rates in the CON group, in contrast to stable or increasing values in the MAFLD groups (CON vs. MAFLD delta-values, p<0.01, p=0.02 and p=0.04) , respectively) . EGP was similar in all groups throughout the LowG period and rose similarly when increasing glucagon infusion rate.

Conclusions: Patients with MAFLD, MAFL as well as MASH, have an impaired glucagon-mediated suppression of VLDL-TG secretion which is a probable contributing factor to the dyslipidemia and the increased cardiovascular risk observed in individuals with MAFLD. NCT04042142

Disclosure

S.Heebøll: None. J.R.Risikesan: None. H.Gronbaek: Other Relationship; ARLA, Research Support; AbbVie Inc., Intercept Pharmaceuticals, Inc., Speaker's Bureau; AstraZeneca, Novartis AG. E.Søndergaard: None. S.Nielsen: None.

Funding

Independent Research Fund Denmark (9039-00177B and -00278B) and Aase og Ejnar Danielsens Fond
289-OR: Automated Insulin Delivery Use among 12,065 T1D Exchange Registry Participants
Authors: LIU JINGWEN , MILLER KELLEE , KELLY CAITLIN , CHAPMAN KATHERINE S.M. , PETER MEGAN , FINAN DANIEL , NGUYEN HUYEN , LAFERRIERE KELSIE , LEON CAROLINA , WOLF WENDY
Published: May 2022

Use of automated insulin delivery (AID) in people with type 1 diabetes (T1D) has increased in recent years. We analyzed data from the T1D Exchange Registry - an online longitudinal study following adults and children with T1D - to describe characteristics of AID use and its association with self-reported HbA1c, occurrence of diabetic ketoacidosis (DKA) symptoms, and occurrence of severe hypoglycemia events (SHE) . Of 12,065 participants (69.5% female, 87.5% non-Hispanic White, mean age 37.9 yrs, mean T1D duration 19.9 yrs) , 26.4% reported using AID, 43.6% using insulin pump without AID, and 30.0% using multiple daily injections (MDI) . Private insurance was reported in 77.4% of AID users, 74.9% pump without AID, and 66.3% MDI. Among the 3,185 AID users, 50.6% used predictive low glucose suspend (PLGS) features, including Medtronic 640G and Tandem Basal-IQ; 49.4% used hybrid closed-loop (HCL) , including DIY looping, Medtronic Auto Mode, and Tandem Control-IQ. Average HbA1c was lower in AID users than those using MDI and pump without AID; Incidence of SHE was lower among HCL users compared with PLGS users and AID users compared with MDI users (Table 1) . These cross-sectional real-world data support findings of previous clinical studies showing significant improvements in HbA1c with AID use, with HCL use providing additional protection against SHE.

Disclosure

J.Liu: None. W.Wolf: None. K.Miller: Research Support; Dexcom, Inc., Tandem Diabetes Care, Inc. C.Kelly: None. K.S.M.Chapman: None. M.Peter: None. D.Finan: None. H.Nguyen: None. K.Laferriere: None. C.Leon: None.
291-OR: Using the Performance in Exercise and Knowledge (PEAK) Guidelines Incorporated in a Smartphone-Based Decision Support System Improves Glucose Outcomes during Free-Living Exercise
Authors: WILSON LEAH M. , JACOBS PETER G. , GUILLOT FLORIAN H. , TYLER NICHOLE S. , KUSHNER TAISA , ESPINOZA ALEJANDRO Z. , MOSQUERA-LOPEZ CLARA M. , PINSONAULT JOSEPH , DODIER ROBERT , OGANESSIAN SOS M. , BRANIGAN DEBORAH , GABO VIRGINIA , EOM JAE H. , YOUSSEF JOSEPH EL , WINTERS-STONE KERRI , CASTLE JESSICA R.
Published: May 2022

DailyDose is a smart-phone decision support system developed at Oregon Health & Science University that uses Dexcom G6 CGM and Medtonic’s InPen. The app calculates insulin doses using CGM value and trend, insulin-on-board, carbohydrate amount, and exercise information. Insulin dosing and carbohydrate intake recommendations before and after exercise are adjusted according to the 2017 consensus statement by Riddell et al. known as the PEAK Guidelines. Twenty-four adults with T1D, using multiple daily injections of insulin at baseline, completed a two-week run-in period then used the DailyDose intervention for 8 weeks. Participants completed 3 at-home exercise sessions per week, one aerobic exercise video and two other sessions of their choice. We examined the impact of the use of PEAK guidelines on glucose outcomes during exercise comparing 176 exercise sessions done during run-in and 471 sessions done during the intervention period. Glucose outcomes were assessed from start of exercise to 4 hours after the start or until either a meal was consumed, insulin dosed or new exercise session initiated. Mixed effects analysis was used to determine significance of the intervention on glucose outcomes. The nadir of the glucose was lower for the run-in compared with the intervention (120.6 vs. 130.9 mg/dL, P=.012) . Change in glucose from the start of exercise to the nadir was 58.0 for the run-in versus 46.9 for the intervention period (P=.016) . Time in hyperglycemia (>180mg/dL) during the exercise periods trended toward being lower during the intervention (43.8% run-in, 35.0% intervention, P=.059) , as did time in range of 70-180 mg/dL, (54.2% run-in, 62.2% intervention, P=.081) . There was no difference in time in hypoglycemia. Data suggest that use of PEAK within a decision support app can help prevent more severe glucose drops during and after exercise with a trend toward improving time in range.

Disclosure

L.M.Wilson: n/a. S.M.Oganessian: None. D.Branigan: None. V.Gabo: None. J.H.Eom: None. J.El youssef: None. K.Winters-stone: None. J.R.Castle: Advisory Panel; Insulet Corporation, Novo Nordisk, Zealand Pharma A/S, Stock/Shareholder; Pacific Diabetes Technologies. P.G.Jacobs: Other Relationship; Pacific Diabetes Technologies, Research Support; Dexcom, Inc. F.H.Guillot: Stock/Shareholder; Pacific Diabetes Technologies. N.S.Tyler: None. T.Kushner: Consultant; Tandem Diabetes Care, Inc. A.Z.Espinoza: None. C.M.Mosquera-lopez: None. J.Pinsonault: None. R.Dodier: None.

Funding

The Leona M. and Harry B. Helmsley Charitable Trust (Grant 2018PG-T1D001) , OHSU Medical Research Foundation, Supplies provided by Dexcom
296-OR: Single-Cell Multiomic Analysis of the Human Pancreas in Type 1 Diabetes
Authors: MELTON REBECCA , BEEBE ELISHA , ZENG CHUN , MILLER MICHAEL T. , WANG GAOWEI , MCGRAIL CAROLYN , MUMMEY HANNAH , KUSMARTSEVA IRINA , ATKINSON MARK A. , PREISSL SEBASTIAN , SANDER MAIKE , GAULTON KYLE J.
Published: May 2022

The cis-regulatory programs of specific cell types in the pancreas that are affected in type 1 diabetes (T1D) are poorly understood. Single cell technology enables detailed interrogation of genomic profiles of cell types within a heterogeneous tissue, and when applied to samples across disease states can reveal cell type-specific changes in disease. In this study we applied single nucleus RNA-seq (snRNA-seq) and single nucleus ATAC-seq (snATAC-seq) , as well as paired multiome (snRNA-seq+snATAC-seq) , to cryopreserved whole pancreas samples from 34 donors including 13 control, 9 T1D autoantibody positive (Aab+) , 7 early T1D (1< yr) and 5 late T1D donors in the nPOD biorepository. Clustering of 313,078 gene expression and 342,863 accessible chromatin profiles after extensive processing and filtering resolved pancreatic endocrine, exocrine, immune, stellate, glial and endothelial cell types, as well as known and novel cell sub-types for example REG1A+ acinar cells and MUC5b+ ductal cells. There were marked changes in the abundance of many cell types and sub-types across disease states, including a significant reduction in beta cells and increase in immune cell populations in T1D compared to control. Differential analysis of gene expression and cis-regulatory element (cCRE) activity in each cell type revealed changes in early and late T1D, as well as in T1D Aab+. In beta cells, 2 and 2,177 genes and 1,080 and 9,177 cCREs had differential activity in early and late T1D, respectively, and early and late T1D genes in beta cells were enriched for distinct molecular processes related to interferon gamma signaling and cell death. Intersecting differential beta cell cCREs with comprehensive T1D genetic fine-mapping revealed 13 T1D signals where candidate variants mapped in a differential beta cell cRE of which were proximal to a differentially expressed gene, such as at the GLIS3 locus. Together these results provide insight into the role of cis-regulatory programs in beta cells and other pancreatic cell types in T1D.

Disclosure

R.Melton: None. S.Preissl: None. M.Sander: None. K.J.Gaulton: Consultant; Genentech, Inc., Stock/Shareholder; Neurocrine Biosciences, Inc., Vertex Pharmaceuticals Incorporated. E.Beebe: None. C.Zeng: None. M.T.Miller: None. G.Wang: None. C.Mcgrail: None. H.Mummey: None. I.Kusmartseva: None. M.A.Atkinson: None.

Funding

Ruth Kirschstein Institutional National Research Service Award T32 (GM008666) National Institutes of Health (DK120429)
299-OR: Molecular and Physiological Consequences of the Diabetes-Related PGC1A Gly482Ser Polymorphism
Authors: GALIPEAU MARIA , JOUVET NATHALIE , COURTY EMILIE , VANDENBEEK ROXANNE , KHAN NAVEEN P. , BOUYAKDAN KHALIL , NIAN CUILAN , IORIO CATERINA , SCOTT DANIEL D. , FARAJ MAY , OEFFINGER MARLENE , LYNN FRANCIS C. , SCREATON ROBERT A. , ALQUIER THIERRY , ESTALL JENNIFER L.
Published: May 2022

Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1A) is a nuclear transcriptional coregulator that plays a major role in the control of metabolism and mitochondrial biogenesis. We showed that a diabetes-linked single nucleotide polymorphism (SNP rs8192678) within the coding region of PPARGC1A gene (Gly482Ser) results in decreased protein stability and half-life in liver and beta-cell lines and human induced pluripotent stem cells (iPSCs) . Our mass spectrometry data suggest that degradation of the S482 variant is mediated by phosphorylation at amino acid 482 when a serine is present. A kinome screen identified three potential kinases (NEK2, MARK4 and S6K2) that can modify this site. We found that mutation of the mouse homolog at the conserved site (serine to glycine) similarly stabilized mouse PGC1A. To study the physiological consequences of this SNP, we generated whole-body homozygous glycine (G/G) , serine (S/S) and heterozygous (S/G) mice. We analyzed various metabolic parameters in male (N=10-per genotype) and female (N=8-9) mice subjected to standard chow or high fat, high fructose diet (HFHF) for 14 or 24 weeks. We found that G/G male and female mice had increased caloric intake using metabolic cages without increased body weight. Male mice on a HFHF diet carrying a glycine allele (G/G or S/G) were more resistant to insulin in an insulin tolerance test (ITT) , secreted less insulin in response to a mixed-meal challenge and had decreased glucose uptake in muscle and adipose tissue. In line in humans, non-diabetic subjects with G/G (N=20) or G/S (N=22) variants oxidize more fat while those with S/S variant (N=6) oxidize more carbohydrate over 6-hours following the ingestion of a high-fat meal (68% fat, 18% carbohydrate) .

In summary, these results demonstrate that differences in PGC1A stability associated with phosphorylation at site 482 may lead to differences in glucose and fat metabolism, which could explain the link between this SNP and metabolic diseases.

Disclosure

M.Galipeau: None. M.Faraj: None. M.Oeffinger: None. F.C.Lynn: None. R.A.Screaton: None. T.Alquier: None. J.L.Estall: None. N.Jouvet: None. E.Courty: None. R.Vandenbeek: None. N.P.Khan: None. K.Bouyakdan: None. C.Nian: None. C.Iorio: None. D.D.Scott: None.

Funding

CIHR (PJT-148771) CIHR (PJT-168853)
30-LB: Multicenter, Randomized Controlled Clinical Investigation Evaluating a Unique Micro Water Jet Technology Device Versus Standard Debridement in the Treatment of Diabetic Foot
Authors: ARMSTRONG DAVID G. , ZELEN CHARLES
Published: May 2022

Background: Proper debridement of the wound base is critical to facilitate wound granulation and closure in non-healing diabetic foot ulcers (DFUs) . A unique micro water jet device has been developed that precisely cleans acute and chronic wounds in a tissue-preserving manner while performing a precise mechanical cleaning and stimulation of the wound base to enhance granulation and healing. In this trial the device was used to treat non healing DFUs.

Methods: 85 patients were screened, and 50 patients were enrolled for the preliminary analysis, in a two arm randomized controlled trial. Diabetic foot wounds that were non-healing for at least 4 weeks, with adequate blood flow and were void of clinical infection or osteomyelitis were entered into 2 weeks of screening. Those that met all the qualifications were randomized to receive either weekly micro jet wound debridement or standard sharp debridement along with SOC wound dressing and offloading. Both groups were followed for 16 weeks. The study endpoints included healing at 16 weeks as well as percent area wound reduction (PAR) over the treatment phase of 16 weeks.

Results: At 16 weeks 72% (18/25) of the Micro Water jet treated DFUs healed compared with 40% (10/25) treated with standard sharp debridement p=0.023 (unadjusted) . Furthermore, at 16 weeks, the percent area reduction (PAR) was 86.5% (SD: 25.60) for the wounds treated with the Micro Water Jet versus 35.1% (SD: 164.47) with standard sharp wound debridement p=0.021 (unadjusted) . The safety analysis showed with regard to wound related adverse events (AE) and serious adverse events (SAE) ; 1 AE and 1 SAE occurring in the Micro Water jet group versus 9 AEs and 4 SAEs in the standard sharp debridement group.

Conclusion: The micro water jet device was able to statistically significantly close more refractory DFUs over 16 weeks, with a significant difference in wound area reduction that should be noted. Further evaluation with larger randomized controlled trials are warranted to validate these initial promising findings.

Disclosure

D. G. Armstrong: None. C. Zelen: Research Support; Geistlich Pharma, Medaxis LLC, Musculoskeletal Transplant Foundation, PolarityTE, Inc.

Funding

Medaxis LLC (A0010)
311-OR: Regulation of Brown Adipocyte Differentiation and Thermogenesis by Prostaglandin F2a
Authors: FADUMIYE ESTHER , KODANI SEAN , KIEBISH MICHAEL , BUSSBERG VALERIE , TSENG YU-HUA
Published: May 2022

Brown adipocytes hold the potential to mitigate body fat accumulation and type 2 diabetes (T2D) via their specialized function in dissipating energy as heat, a process known as thermogenesis. To fuel their function, brown adipocytes release the bond energy of fat through lipolysis and β-oxidation; then, uncoupling cellular respiration releases this energy as physical heat. In addition to their energy-dissipating function, brown adipocytes can release factors, such as lipids, metabolites, peptides, or microRNA, to regulate metabolism. Signaling lipids have demonstrated roles in regulating thermogenesis in brown adipocytes by regulating lipid uptake and utilization. To further explore these pathways, we performed signaling lipidomics analysis in in vitro differentiated human brown adipocytes and found 15-keto-PGF2α was increased when treated with forskolin, an adenylyl cyclase activator that mimics adrenergic stimulation. Previous studies have shown PGF2α, the parent molecule of 15-keto-PGF2α, inhibits maturation, or adipogenesis, in white adipocyte cell lines by preventing the expression of key adipogenesis genes, such as PPARγ and C/EBPα. Similarly, PGF2α inhibits thermogenic gene expression in brown adipocyte cells. To explore and compare the functional activities of PGF2α and 15-keto-PGF2α, we characterized the dose-response relationship of these lipids on thermogenic gene and protein expression. We found that 15-keto-PGF2α is not as potent as PGF2α at inhibiting both thermogenic gene and protein expression. This suggests the conversion of PGF2α to 15-keto-PGF2α represents a significant signaling event to promote thermogenesis in brown adipocytes. Interestingly, carbonyl reductase 1, an enzyme that catalyzes this conversion, is regulated by treatment with the adrenergic agonist, norepinephrine, in vitro and by cold exposure in vivo. Targeting this conversion may be an attractive approach towards activating thermogenesis to mitigate obesity and T2D.

Disclosure

E.Fadumiye: None. S.Kodani: None. M.Kiebish: None. V.Bussberg: None. Y.Tseng: Consultant; Cellarity.

Funding

National Institutes of Health (R01DK122808)
32-LB: Role of Telehealth in Improving Health Care Quality in Type 2 Diabetes in a Rural Community-Based Clinical Practice
Authors: GURURAJ SUPRAJA , ASFA AMIR , HANLEY LESLIE C. , YADAV YOGESH R. , BASHORE RANDALL T. , BASU RITA , BASU ANANDA
Published: May 2022

Use of continuous glucose monitoring (CGM) facilitates better management of type 2 diabetes (T2D) in outpatient clinics in academic medical centers. In a Quality Improvement project, we evaluated the effects of telehealth aided by CGM on HbA1c and percent time in range (TIR 70-180 mg/dl) in patients with T2D over a 6-month duration. Diabetes management advice based on intermittent CGM use was provided via phone by an academic endocrinologist to the clinical pharmacist at a rural community clinic. Inadequately controlled (HbA1c > 8%) T2D patients (n=27) on at least one antidiabetic drug were included and were monitored over a 6 month period, baseline (V1) , 3 months (V2) and 6 months (V3) . All patients received standard of care (SOC) treatment. On each visit, 12 patients (age 59 8y, BMI 36.2 3.6kg/m2, HbA1C 9.3 1.3%) received a professional CGM for 2 weeks. Thereafter, the devices were removed and analyzed. The PCP implemented medication changes based on recommendations by the endocrinologist to the clinical pharmacist. The other 15 patients (age 60 8y, BMI 32 4 kg/m2, HbA1C 9.1 1.6%) underwent the same schedule without CGM or telehealth consultations. There were no significant differences in age or HbA1c between groups at baseline. HbA1c (%) decreased (Δ -1.0 ± 1.4; p=0.03) , and CGM TIR (%) increased (Δ +24.3 ± 38.7; p=0.05) at V3 vs. V1 in the telehealth group. However, weight, CGM time below and above ranges (%) did not differ (p>0.05) statistically. In contrast, there were no significant differences in HbA1c (Δ +0.4 ± 1.7; p=0.3) between V3 and V1 in the SOC without telehealth group. Our results show that intermittent CGM use coupled with tele-consultation with diabetes expert improves glucose control and care quality in patients with T2D in community based health practice. This strategy could potentially mitigate existing health care disparities between suburban/rural-based community health practices and academic medical centers, thus closing the gaps in quality of care.

Disclosure

S. Gururaj: None. A. Asfa: None. L. C. Hanley: None. Y. R. Yadav: None. R. T. Bashore: None. R. Basu: Consultant; Sparrow Pharmaceuticals Inc, Research Support; Abbott Diabetes, AstraZeneca. A. Basu: Speaker’s Bureau; Zealand Pharma A/S.

Funding

Virginia Department of Health (GS11963)
32-OR: The Advancing Care for T1D Obesity Network (ACT1ON) Sequential Multiple Assignment Randomized Trial Pilot Re-randomization Results
Authors: IGUDESMAN DARIA , CRANDELL JAMIE , POKAPRAKARN TEERANAN , CORBIN KAREN , ZAHARIEVA DESSI P. , ADDALA ANANTA , THOMAS JOAN , CASU ANNA , RIDDELL MICHAEL , PRATLEY RICHARD E. , KOSOROK MICHAEL R. , MAAHS DAVID M. , MAYER-DAVIS ELIZABETH J.
Published: May 2022

Background: Sequential Multiple Assignment Randomized Trials (SMARTs) efficiently address practical treatment comparison questions and adapt dynamically based on response. They may be useful for development of approaches to co-manage weight and glycemia T1D, which is critical yet challenging.

Methods: Our SMART pilot with three diet periods enrolled young adults with T1D (BMI 27-39.9 kg/m²) . Participants were re-randomized after ∼3 months on the hypocaloric Look AHEAD (Low Fat) or Low Carbohydrate (Low Carb) ; or Mediterranean (Med, not calorie restricted) diet if <2% weight was lost, HbA1c increased ≥0.5%, diet was unacceptable, or hypoglycemia increased. We present descriptive statistics for weight, HbA1c, and re-randomization for diet period 1 pre-COVID before shifting to a virtual protocol.

Results: The proportion re-randomized was 57.9% and did not vary by diet. Weight was lost overall but insufficient weight loss was the most common reason for re-randomization for Low Fat and Med. An HbA1c increase ≥0.5% was most common on Med. Low diet acceptability was the most common reason for re-randomization on Low Carb.

Conclusions: We achieved safe weight loss among young adults with T1D but observed heterogeneity in reasons for re-randomization by diet, although differences were not statistically significant. A fully-powered efficacy trial may confirm our findings.

Disclosure

D.Igudesman: None. R.E.Pratley: Other Relationship; Bayer AG, Corcept Therapeutics, Dexcom, Inc., Hanmi Pharm. Co., Ltd., Merck & Co., Inc., Metavention, Novo Nordisk, Pfizer Inc., Poxel SA, Sanofi, Scohia Pharma Inc., Sun Pharmaceutical Industries Ltd. M.R.Kosorok: n/a. D.M.Maahs: Advisory Panel; Abbott Diabetes, Eli Lilly and Company, Medtronic, Novo Nordisk, Sanofi, Consultant; Aditx Therapeutics, Inc., Biospex. E.J.Mayer-davis: None. J.Crandell: n/a. T.Pokaprakarn: None. K.Corbin: None. D.P.Zaharieva: Research Support; Insulet Corporation, International Society for Pediatric and Adolescent Diabetes, Leona M. and Harry B. Helmsley Charitable Trust. A.Addala: None. J.Thomas: None. A.Casu: None. M.Riddell: Advisory Panel; Zealand Pharma A/S, Zucara Therapeutics, Consultant; Eli Lilly and Company, Jaeb Center for Health Research, Speaker's Bureau; Dexcom, Inc., Eli Lilly and Company, Novo Nordisk.

Funding

National Institutes of Health 1DP3DK113358
326-OR: Type 2 Diabetes, Chronic Kidney Disease, and Major Cardiovascular Events in Patients with Established Cardiovascular Disease
Authors: SPRENGER LUKAS , MAECHLER MAXIMILIAN , VONBANK ALEXANDER , LARCHER BARBARA , MADER ARTHUR , LEIHERER ANDREAS , MUENDLEIN AXEL , DREXEL HEINZ , SAELY CHRISTOPH H.
Published: May 2022

Type 2 diabetes (T2DM) and chronic kidney disease (CKD) both confer a high risk of cardiovascular disease (CVD) , and these conditions frequently coincide. The aim of this study was to investigate the single and joint effects of T2DM and CKD on major cardiovascular events (MACE) in patients with established cardiovascular disease.

We prospectively investigated 1738 patients with established cardiovascular disease - angiographically proven coronary artery disease (CAD) or sonographically proven peripheral artery disease (PAD) - over 10.0±4.7 years.

MACE occurred more frequently in T2DM patients (n=575) than in non-diabetic subjects (42.5% vs. 29.8%, p<0.001) and in patients with CKD (eGFR <60ml/min/1.73m2; n=302) than in those who did not have CKD (52.2% vs. 30.1%, p<0.001) . When both, T2DM and CKD were considered, 996 subjects had neither T2DM nor CKD, 440 had T2DM but not CKD, 172 did not have diabetes but had CKD, and 130 had both T2DM and CKD. Compared to the incidence of MACE among patients with neither T2DM nor CKD (26.5%) , MACE occurred more frequently in patients with T2DM who did not have CKD (38.2%; p<0.001) as well as in non-diabetic patients with CKD (48.0%; p<0.001) ; the incidence of MACE was highest in patients with both, T2DM and CKD (57.8%; p<0.001) , in whom it was higher than in those with T2DM but not CKD (p<0.001) or those without T2DM but with CKD (p=0.007) ; the incidence of MACE was higher in non-diabetic CKD patients than in T2DM patients who did not have CKD (p=0.040) . In Cox regression analysis, T2DM (HR=1.53 [1.29-1.83]; p<0.001) and CKD (HR=1.85 [1.51-2.26]; p<0.001) proved to be mutually independent predictors of MACE after adjustment for age, sex, BMI, hypertension, history of smoking, LDL-C, HDL-C and HbA1c.

We conclude that T2DM and CKD in patients with established cardiovascular disease are mutually independent predictors of MACE. Cardiovascular disease patients with both CKD and T2DM are at an extremely high risk for MACE.

Disclosure

L.Sprenger: None. M.Maechler: None. A.Vonbank: None. B.Larcher: None. A.Mader: None. A.Leiherer: None. A.Muendlein: None. H.Drexel: None. C.H.Saely: None.
327-OR: Preliminary Outcomes of a Social Media–Based Diabetes Intervention among Low-Income Chinese Immigrants
Authors: HU LU , ISLAM NADIA , JIANG NAN , TAMURA KOSUKE , JAGANNATHAN RAM , KHARMATS ANNA Y. , BUBU OMONIGHO , SEVICK MARY ANN
Published: May 2022

Purpose: Mobile health holds strong promise to increase access to diabetes self-management education (DSME) programs in underserved communities. In this report, we examined the preliminary outcomes of a social media-based DSME intervention in low-income Chinese immigrants with type 2 diabetes (T2D) .

Methods: We conducted a single-group pilot study in 30 Chinese immigrants with T2D living in NYC in 2020. Over 12 weeks, participants received 2 brief culturally and linguistically tailored DSME videos each week via WeChat, a free and popular social media app among Chinese immigrants. Participants completed baseline and 6-month surveys with self-efficacy, diabetes self-care behaviors, dietary intake, and physical activity measures. Paired t-tests were used to examine changes over time.

Results: Of the 30 participants, mean (SD) age was 61.2 (6.7) years, 70.0% were women, 63.3% reported high school education, 84.0% reported annual family income of < $25,000, 63.3% were married, and 86.7% had limited English proficiency. Compared to baseline, there were significant improvements in participants’ self-efficacy, diabetes self-care behaviors, dietary intake and physical activity at 6 months (see Table 1) .

Conclusions: Our social media-based DSME intervention demonstrated promising results in improving psychosocial and behavioral outcomes in low-income older Chinese immigrants with T2D.

Disclosure

L.Hu: None. N.Islam: None. N.Jiang: None. K.Tamura: None. R.Jagannathan: None. A.Y.Kharmats: None. O.Bubu: None. M.Sevick: None.

Funding

NIH K99MD0128 (PI Dr. Lu Hu) ; NIH R00MD0128 (PI Dr. Lu Hu) , Dr. Anna Kharmats was supported by a postdoctoral training grant from the National Institutes of Health (5T32HL129953-04)
339-OR: Oral Small-Molecule GLP-1R Agonist Danuglipron Robustly Reduces Plasma Glucose and Body Weight after Eight Weeks in Japanese Adults with Type 2 Diabetes Mellitus
Authors: ONO RYOSUKE , FURIHATA KENICHI , ICHIKAWA YOSHIHIKO , NAKAZURU YOSHIOMI , BERGMAN ARTHUR , GORMAN DONAL N. , SAXENA ADITI R.
Published: May 2022

Danuglipron is an oral small molecule glucagon-like peptide-1 receptor (GLP-1R) agonist shown to reduce plasma glucose and body weight after 28 days of treatment in adults with type 2 diabetes mellitus (T2DM) . This randomized, double-blind (sponsor-open) , placebo-controlled, Phase 1 study investigated the safety, tolerability, pharmacokinetics, and pharmacodynamics of danuglipron in Japanese patients with T2DM. A total of 37 patients with T2DM inadequately controlled on diet and exercise alone were randomized to twice-daily (BID) oral doses of placebo or multiple, ascending doses of danuglipron titrated to 40 mg, 80 mg, and 120 mg for 8 weeks. Multiple, oral doses of danuglipron were generally safe in Japanese participants with T2DM and resulted in approximate dose-proportional increases in exposure and significant reductions in fasting plasma glucose (FPG) , 24-hour mean daily glucose (MDG) , glycated hemoglobin (HbA1c) , and body weight (Table) . Most adverse events (AEs) were mild or moderate, with AEs of nausea, vomiting, abdominal discomfort, diarrhea, and headache reported most frequently. There were no deaths and no serious AEs related to dosing of danuglipron. No clinically significant adverse trends in labs, electrocardiogram, or vital sign abnormalities were apparent.

Disclosure

R.Ono: Employee; Pfizer Japan Inc. K.Furihata: Other Relationship; Eli Lilly and Company, Pfizer Japan Inc. Y.Ichikawa: Employee; Pfizer Inc., Stock/Shareholder; Pfizer Japan Inc. Y.Nakazuru: Employee; Pfizer Japan Inc., Stock/Shareholder; Pfizer Inc. A.Bergman: Employee; Pfizer Inc., Stock/Shareholder; Pfizer Inc. D.N.Gorman: Employee; Pfizer Inc. A.R.Saxena: Employee; Pfizer Inc.

Funding

Sponsored by Pfizer Inc.
342-OR: Low Incretin Effect Is Associated with Longitudinal Decline of Beta-Cell Function and Insulin Sensitivity in Obese Youth
Authors: GALDERISI ALFONSO , LAT JESSICA O. , SAMUELS STEPHANIE , PIERPONT BRIDGET , VAN NAME MICHELLE A. , SANTORO NICOLA , CAPRIO SONIA
Published: May 2022

Background: We assessed the longitudinal trajectory of beta-cell function with respect to baseline incretin effect in youth with obesity.

Methods: At baseline and two years, youth with obesity and 2-h glucose ≥ 120mg/dL underwent a 3-hour OGTT and isoglycemic intravenous glucose infusion (to quantify the incretin effect) . Participants were stratified into three tertiles based on the baseline incretin effect. The oral minimal model quantified beta cell function (oDI) and insulin sensitivity (SI) .

Results: Thirty participants completed the assessments [follow-up: age 18.6±2.4y, 19F; BMI 38.6±7.4 kg/m2, NGT/IGT/T2D 12/17/1]. At 2 years, 2-h glucose improved in the high incretin group (p=0.047) , but was stable in the middle- and low- incretin groups (panel G) . At 2 years, the baseline high-incretin group exhibited a lower 60-min glucose (p=0.026) than the low-incretin group, with similar 120-min glucose (p=0.696) , despite the low-incretin cohort’s relative increase in early insulin secretion (panel D, F) . The low-incretin tertile also exhibited a reduced β cell function (oDI) at follow-up (panel I) (p=0.044) mainly due to lower insulin sensitivity (panel H) (p=0.013) .

Conclusion: Low incretin effect is associated with a longitudinal decline of beta cell function and decreased insulin sensitivity, despite greater first-phase insulin secretion.

Disclosure

A.Galderisi: None. J.O.Lat: None. S.Samuels: None. B.Pierpont: None. M.A.Van name: Research Support; Provention Bio, Inc. N.Santoro: None. S.Caprio: None.

Funding

National Institute of Diabetes and Digestive and Kidney Diseases/NIH/DHHS (16-004945)
348-OR: Glycine and Branched-Chain Amino Acids (BCAA) Metabolic Signature in Youth with Obesity and Type 2 Diabetes (T2D)
Authors: AYASH HEBA EL , MOHAMMAD MAHMOUD A. , SHAWAR REEM S. , KANCHI RUPA S. , SHARMA SUSAN , PUYAU MAURICE R. , COARFA CRISTIAN , BACHA FIDA
Published: May 2022

BCAAs are associated with increased risk for T2D in adults, while glycine (Gly) appears to be have an inverse relationship. β-cell function is central to the development of T2D in youth. The relationship of Gly and BCAA to β-cell function in youth is not clear.

We investigated the relationship between Gly vs. the BCAA: Leucine (Leu) , Isoleucine (Ile) and Valine (Val) , to insulin sensitivity (IS) and β-cell function in youth across the spectrum of glycemia.

Adolescents (65 female/62 male; 15.5±1.9 y.o.; 30 with normal weight normal glucose tolerance (NW-NGT) , 33 obese-NGT, 34 prediabetes, and 30 T2D) underwent assessment of AA concentrations (mass spectrometry) , fasting and at steady state (SS) of a 3-hr hyperinsulinemic-euglycemic clamp (in-vivo IS) ; insulin secretion by 2-hr hyperglycemic clamp; adipokines, body composition (DXA) and visceral fat (MRI) . The disposition index (DI) (measure of β-cell function) = first phase insulin x IS per fat free mass (DIFFM) . We performed analysis of variance (adjusting for sex, race-ethnicity and Tanner stage) and correlation analyses.

Fasting and SS-Gly were lower and SS-BCAA higher in the groups with obesity compared with NW with post-hoc significant differences in T2D vs. NW (p<0.0for fasting and SS-Gly, SS-Ile, and p=0.02 for SS-Val) and in prediabetes vs. NW (for Gly, Val and Ile) . Fasting and SS-Gly negatively and SS-BCAA positively associated with %body fat, waist/hip, and visceral fat, while Gly positively and BCAA negatively related to adiponectin. Fasting and SS-Gly (r=0.4, p<0.001) positively and SS-BCAA (r=-0.4 for Val, Leu, Ile, p<0.001) negatively related to ISFFM. Gly positively (r=0.27, p=0.005) , SS-Ile (r=-0.26, p=0.006) inversely related to DIFFM.

Gly is positively related to IS and β-cell function and negatively to adiposity measures, with opposite relationships observed for BCAA. A metabolic signature of low Gly and elevated BCAA may constitute a biomarker to identify youth at risk for β-cell failure.

Disclosure

H.El ayash: None. M.A.Mohammad: None. R.S.Shawar: None. R.S.Kanchi: None. S.Sharma: None. M.R.Puyau: None. C.Coarfa: None. F.Bacha: Other Relationship; AstraZeneca, Takeda Pharmaceutical Company Limited, Research Support; National Institute of Diabetes and Digestive and Kidney Diseases, U.S. Department of Agriculture.

Funding

USDA-ARS
35-LB: Classification in Koreans with Oral Antidiabetic Agents by Diabetes Education and Psychological Support Needs Using Q Methodology
Authors: CHA EUNSEOK , SHIN MYOUNGHWAN , JANG HYESUN , JOUNG KYONG HYE , KIM HYUN JIN , FAULKNER MELISSA S.
Published: May 2022

Objective: To classify diabetes attitude, wishes and needs affecting diabetes self-management behaviors in persons with type 2 diabetes (T2D) taking oral medication.

Methods: Q-methodology, a mixed method of inquiry with bottom up-logic, was used to identify psychological phenotypes. Data using 33 Q-samples collected from 51 Q-Korean sorters (35men; 16 women) were analyzed by factor analysis using varimax orthogonal rotation (PQ Method Program, Version 2.35) . The Summary of Diabetes Self-Care Activity measure and A1C in the past 6 months were included to obtain comprehensive understanding for managing diabetes.

Findings: A total of 34% variance was explained by 4 factors: Factor 1 (n=18) : moderate management with low confidence (age=60.0±12.2; A1C=7.06±1.98) , Factor 2 (n=15) : good management with high confidence (age= 68.3±9.7; A1C=6.60±0.59) , Factor 3 (n=6) : good management, necessitating assurance from trustful others including health care providers and logistic support (age=65.8±8.4; A1C=6.53±0.86) , Factor 4 (n=12) : poor management with low confidence and behavioral skills to be improved (age= 56.4±14.1; A1C= 7.53 ±1.14) .

Conclusions: Psychosocial screening affecting diabetes self-management behaviors needs to be regularly assessed to provide precision health in T2D education and support. Since those in a younger age were associated with poor diabetes management, further investigation is warranted to identify life stage care needs for T2D education and support.

Disclosure

E. Cha: None. M. Shin: None. H. Jang: None. K. Joung: None. H. Kim: None. M. S. Faulkner: None.

Funding

Korea Research Foundation (NRF-2019R1A2C1087199)
353-OR: Determining the Sequence of Microvascular Complications: Results of Multistate Markov Modelling in the Diabetes Control and Complications Trial (DCCT)
Authors: LOVBLOM LEIF ERIK , BRIOLLAIS LAURENT , TOMLINSON GEORGE , PERKINS BRUCE A.
Published: May 2022

Screening for neuropathy is complex and underperformed in practice. If neuropathy rarely occurs first, screening for it could be delayed until retinopathy or nephropathy are documented. To address this, we aimed to definitively determine the sequence of microvascular complications in the natural history of type 1 diabetes (T1D) . Using data available from the public NIDDK Repository (1983-2012) , independent of the DCCT/EDIC research group, we performed a multistate analysis using biostatistics techniques for complex trivariate processes of the 1441 participants with T1D. Retinopathy (‘Eye’, E) , nephropathy (‘Kidney’, K) , and neuropathy (‘Nerve’, N) were each screened repeatedly and defined by the early-stage phenotypes (Figure 1) . Our model accounted for intermittent ascertainment and differing screening schedules. At baseline, participants had mean age 27±7 years and duration 6±4 years. Markov model simulations started in the absence of complications (Ø) . Eye was the most common initial complication (49%) , followed by nerve (28%) , and kidney (22%) . Median time to first complication was 5.3 years. 4% had no complications through follow-up. While retinopathy is conclusively most common, the high frequency of other initial complications reinforces the current practice of unselected early screening for all three, including neuropathy.

Disclosure

L.Lovblom: None. L.Briollais: None. G.Tomlinson: None. B.A.Perkins: Advisory Panel; Abbott Diabetes, Insulet Corporation, Sanofi, Board Member; Novo Nordisk, Other Relationship; Abbott Diabetes, Insulet Corporation, Medtronic, Novo Nordisk, Research Support; BMO Bank of Montreal, Novo Nordisk.

Funding

The Canadian Institutes of Health Research and the public NIDDK Central Repository.