bluuebunny/crossref_metadata_2025_split huggingface dataset:
376-P: The Hypoglycemia Awareness Questionnaire (HypoA-Q) Demonstrates Concurrent and Convergent Validity in Adults with Type 1 Diabetes and Hypoglycemia Unawareness
Authors: MATUS AUSTIN M. , FLATT ANNELIESE , PELECKIS AMY J. , DALTON-BAKES CORNELIA V. , RIEGEL BARBARA , RICKELS MICHAEL R. 
Published: May 2022

Introduction: Impaired awareness of hypoglycemia (IAH) is a risk factor for severe hypoglycemia in type 1 diabetes (T1D) . Current tools to identify IAH are limited in their ability to characterize unawareness and evaluate hypoglycemia severity. The Hypoglycemia Awareness Questionnaire, including the 5-item Short Form awareness subscale (HypoA-Q SF) , was developed to identify IAH and characterize problematic hypoglycemia. We aimed to evaluate HypoA-Q SF’s concurrent and convergent validity.
Methods: Adults with T1D (n=23, 48% male; median age: 36 years, disease duration: 21 years) completed the (a) HypoA-Q SF, (b) Clarke score and (c) hypoglycemia severity (HYPO) score. Those with IAH defined by Clarke score ≥4 (n=12) and HYPO score ≥90th% were established on hybrid-closed loop insulin delivery as part of an ongoing 18-month clinical trial with 6-monthly completion of HypoA-Q, Clarke and HYPO scores. Mann-Whitney U Test was used to evaluate the HypoA-Q SF’s ability to differentiate between those with and without IAH. Repeated measures correlation was used to assess concordance between HypoA-Q SF score and Clarke / HYPO scores over the 18-month period.
Results: At baseline, HypoA-Q SF demonstrated concurrent validity as scores were significantly different between those with and without IAH (W= 110.5, p &lt; .001) . Over the trial, HypoAQ-SF demonstrated convergent validity as repeated measures correlation analysis revealed significant positive relationships with both Clarke (r = 0.62 p &lt; .001) and HYPO (r = 0.48, p&lt;.01) scores.
Conclusion: These findings support the HypoA-Q SF as a tool to identify IAH and evaluate hypoglycemia severity. Further assessment of the HypoA-Q SF alongside gold-standard clamp-derived measures of autonomic symptom and counterregulatory response to hypoglycemia would be of value to determine score thresholds.

Disclosure
A.M.Matus: None. A.Flatt: None. A.J.Peleckis: None. C.V.Dalton-bakes: None. B.Riegel: None. M.R.Rickels: Advisory Panel; Sernova, Corp., Vertex Pharmaceuticals Incorporated, Zealand Pharma A/S, Consultant; L-Nutra Inc.

Funding
National Institutes of Health (R01DK091331; UL1 TR001878; P30 DK19525)
378-P: Network Meta-analysis of Hypoglycemic Treatment Regimens with Potential Risk of Hypoglycemia in Terms of Glycemic Control and Severe Hypoglycemia
Authors: KODAMA SATORU , SATO TAKAAKI , YAMADA MAYUKO H. , YAMAMOTO MASAHIKO , MATSUBAYASHI YASUHIRO , ISHIGURO HAJIME , IWANAGA MIDORI , FUJIHARA KAZUYA , YAMADA TAKAHO , KATO KIMINORI , WATANABE KENICHI , SONE HIROHITO 
Published: May 2022

Insulin and its secretagogues are essential for some patients with type 2 diabetes (T2D) to maintain glycemic control (GC) . However, these drugs are inevitably accompanied by hypoglycemia. Avoiding severe hypoglycemia (SH) is essential considering its poor prognosis. This network meta-analysis aimed to find optimal hypoglycemic treatment regimens for T2D in terms of GC and SH. MEDLINE and EMBASE were used to identify trials comparing 2 or more treatments including insulins and/or SU/glinide and included both GC and SH in study outcomes. Treatment hierarchy was summarized as the surface under cumulative ranking probabilities (SUCRA) . There were 137 eligible trials from which 36 treatments were identified. Insulin plus (+) non-insulin drugs except for SU/glinide (others) had a higher SUCRA for changes in hemoglobin A1c (A1C) compared with only insulins (68.2±5.6% vs. 39.9±6.6%; P=0.01) although the difference in the SUCRA for SH was not significant (P=0.59) . Compared with only insulins, SU/glinide + others had a lower SUCRA for SH (42.4±5.8% vs. 58.5±3.4%, P=0.05) and comparable SUCRA for A1C change (P=1.00) . Cluster analysis indicated that premixed insulin + glucagon-like peptide-1 receptor agonist (Mix-ins+GLP1) consistently belonged to the high-efficacy group for A1C change and achievement of A1C&lt;7.0% and ≤6.5% among the insulin + others therapies. Glinide + thiazolidinedione (TZD) was in groups with high efficacy in terms of A1C change and achievement of A1C&lt;7.0% and high safety regarding SH among SU/glinide + others therapies. Results suggest that in T2D patients adjunctive use of non-insulin drugs (particularly, Mix-ins+GLP1) are recommended for further improving GC and that appropriate combinations of non-insulin hypoglycemic agents (particularly, glinide+TZD) are recommended to avoid SH and extend the time to treatment failure of non-insulin therapy.

Disclosure
S.Kodama: None. K.Kato: None. K.Watanabe: None. H.Sone: Research Support; Astellas Pharma Inc., Eisai Co., Ltd., Kyowa Kirin Co., Ltd., Novo Nordisk, Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Holdings Co., Ltd., Takeda Pharmaceutical Company Limited. T.Sato: None. M.H.Yamada: None. M.Yamamoto: None. Y.Matsubayashi: None. H.Ishiguro: None. M.Iwanaga: None. K.Fujihara: None. T.Yamada: None.
379-P: Patient and Physician Experience of Hypoglycemia during Basal Insulin (BI) Titration in Type 2 Diabetes (T2D) in the U.S.
Authors: HARRIS STEWART B. , MOHAMMEDI KAMEL , BERTOLINI MONICA , WALKER VALERY , CARLYLE MAUREEN H. , ZHOU FANG L. , SEUFERT JOCHEN , ANDERSON JOHN E. 
Published: May 2022

Introduction: Hypoglycemia after BI initiation can negatively impact patient adherence to titration and glycemic target achievement. We report on 2 surveys to better understand patient and physician perspectives/experiences of hypoglycemia during BI titration.
Methods: Adults with T2D and ≥2 claims (≥30 days apart in last 12 months) in the Optum Research Database who initiated BI (February-April 2021) , and physicians who treated ≥30 patients with T2D, ≥1 initiating BI (October 2020-March 2021) , completed a mailed survey.
Results: Responders were 416 patients (51% male, 71% white, mean age 70 years, 72% &gt;years T2D duration) and 386 physicians (45% general practice) . Most physicians reported discussing hypoglycemia signs/symptoms (93%) and how to titrate BI in response to blood glucose (BG) levels (81%) with patients. Among patients who experienced hypoglycemia (49%; Table) , 57% felt very/extremely confident titrating BI during hypoglycemia. Only 35% met fasting BG (FBG) targets. Diabetes Treatment Satisfaction Questionnaire hypoglycemia score (1.34/6) suggests patients felt hypoglycemia was infrequent.
Conclusion: While physicians educate patients on hypoglycemia awareness and BI titration, nearly half of patients surveyed experienced hypoglycemia during titration, and only a third met FBG targets, suggesting new strategies and tools are needed for effective BI titration.

Disclosure
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. K.Mohammedi: Board Member; Lilly, Novo Nordisk, Sanofi, Research Support; Cyclerion Therapeutics, Inc., Speaker's Bureau; Abbott, AstraZeneca. M.Bertolini: Employee; Sanofi. V.Walker: Consultant; Sanofi-Aventis U.S. M.H.Carlyle: None. F.L.Zhou: Employee; Sanofi, Stock/Shareholder; Sanofi. J.Seufert: Advisory Panel; Abbott, Sanofi-Aventis Deutschland GmbH, Research Support; Boehringer Ingelheim International GmbH, Speaker's Bureau; Abbott Diabetes, AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Lilly, Novo Nordisk, Sanofi-Aventis Deutschland GmbH. J.E.Anderson: Advisory Panel; Abbott Diabetes, Consultant; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Gelesis, Novo Nordisk, Sanofi, Speaker's Bureau; Eli Lilly and Company.

Funding
Sanofi
38-LB: Physical Activity and Glycemia among Young Adults with Type 1 Diabetes and Overweight or Obesity—Results from Advancing Care for Type 1 Diabetes and Obesity Network (ACT1ON)
Authors: MUNTIS FRANKLIN R. , IGUDESMAN DARIA , CRISTELLO ANGELICA , THOMAS JOAN , ARRIZON- RUIZ NORA , HOOPER JULIE , ADDALA ANANTA , CRANDELL JAMIE , MAAHS DAVID M. , PRATLEY RICHARD E. , CORBIN KAREN , MAYER-DAVIS ELIZABETH J. , ZAHARIEVA DESSI P. 
Published: May 2022

The ACT1ON pilot study evaluated the feasibility of three dietary strategies to optimize weight and glycemic management among young adults with T1D and overweight or obesity. As a secondary measure, self-reported physical activity (PA) was collected at baseline, 3-, 6-, and 9-months from 68 young adults with T1D (age 25.5 ± 3.1 years, 72.1% female, HbA1c 7.9 ± 1.8%, BMI 30.4 (27.9 - 33.9)) . Using the Global Physical Activity Questionnaire (GPAQ, n=195) and Previous Day Physical Activity Recalls (PDPAR, n=123) , we estimated weekly minutes of moderate-to-vigorous physical activity (MVPA) . Following the COVID-19 outbreak, a subset of participants wore Garmin Vivosmart4® PA trackers for two weeks at each visit (44 measurements from 27 participants) . Mixed effects regression models assessed the relationship between weekly minutes of MVPA and HbA1c using each PA measure. Median weekly minutes of MVPA were 33% lower following the COVID-19 outbreak compared to pre-pandemic PA levels (p=0.02) per the GPAQ, but not PDPAR (-7.7%, p=0.34) . After adjusting for design, demographic, clinical, and dietary variables, a 1 standard deviation increase in weekly minutes of MVPA (GPAQ) was associated with an absolute increase of 0.27% HbA1c (p&gt;0.001) . A small, statistically non-significant association was observed for PDPAR (β=0.13, p=0.19) ; however, we observed a borderline statistically significant association using the PA tracker data (β=0.231, p=0.08) , despite a smaller sample size (n=44) . These results suggest that among young adults with T1D and overweight and obesity, higher levels of PA may lead to challenges in achieving optimal glycemia. Future work is needed to determine how to best support young adults with T1D and overweight and obesity in attaining both their PA and glycemic management goals.

Disclosure
F. R. Muntis: 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. K. Corbin: None. E. J. Mayer-davis: None. D. P. Zaharieva: Research Support; Insulet Corporation, International Society for Pediatric and Adolescent Diabetes, Leona M. and Harry B. Helmsley Charitable Trust. D. Igudesman: None. A. Cristello: None. J. Thomas: None. N. Arrizon- ruiz: None. J. Hooper: None. A. Addala: None. J. Crandell: n/a. D. M. Maahs: Advisory Panel; Abbott Diabetes, Eli Lilly and Company, Medtronic, Novo Nordisk, Sanofi, Consultant; Aditx Therapeutics, Inc., Biospex.

Funding
National Institutes of Health (1DP3DK113358-01)
382-P: Is Sulphonylurea-Induced Hypoglycaemia Hyped among Clinicians?
Authors: VYAS TARJANI C. , SABOO BANSHI D. , CHENNAMSETTI KAUMUDI , KESAVADEV JOTHYDEV , SABOO BHARAT , HASNANI DHRUVI , CHAVDA VIPUL , PANCHAL DHARMENDRA 
Published: May 2022

Aim: To assess the risk of hypoglycaemia (TBR) in persons with diabetes who are on SUs with fairly controlled diabetes (HbA1c between 7 to 8%) .
Background: Sulphonylurea (SU) is conventionally used as a powerful glucose lowering agent and is known to increase the risk of hypoglycaemia. This paper is an attempt to study the effect of SUs on persons with diabetes by introducing continous glucose monitoring (CGM/AGP) which can help clinicians optimise diabetes treatment along with nutrition which can reduce the risk of hypoglycaemia.
Methodology: A retrospective analysis was done at our diabetes care centre. A total of 300 persons with type 2 diabetes on AGP and on SU therapy were studied. Only those persons with HbA1c between 7 to 8%, indicating fairly controlled diabetes were included.
Results: It was observed that no hypoglycaemia was present in 74% of the persons under study as per AGP data. Only 26% had hypoglycaemia grade 1 with less than 5% TBR; 2% had hypoglycaemia in TBR more than 5%, out of which only one person reported symptoms of severe hypoglycaemia. One of the AGP data of person with diabetes is attached in the image.
Conclusion: Judicious use of sulphonylureas does not increase risk of hypoglycaemia (Time Below Range) in type 2 diabetics as traditionally believed.

Disclosure
T.C.Vyas: None. B.D.Saboo: None. K.Chennamsetti: None. J.Kesavadev: None. B.Saboo: None. D.Hasnani: None. V.Chavda: None. D.Panchal: None.
384-P: Experiences with Nasal Glucagon from People with Diabetes and Caregivers, Most Mentioned "Feeling Safe": A Qualitative Study
Authors: MITCHELL BETH , SOWELL FRANCE G. , WILLIAMS PAUL , POON JIAT LING 
Published: May 2022

Hypoglycemia risk and its impact on daily life is always present for people with diabetes and their caregivers (CG) . With the goal of positively impacting the lives of those who use insulin, advances in glucagon and its delivery, have made it ready-to-use, expanding the community of people who could act in an emergency. This qualitative study elicited experiences from people who own one option, nasal glucagon (NG) . Semi-structured 1:1 interviews were conducted in the US with AwD and CGs of children or AwD following a pre-defined concept elicitation guide and analyzed thematically. The sample included 22 AwD (20 T1DM; 2 T2DM) and 7 CGs of people with T1DM (1 Adult, 6 Children) ; female (72%) ; mean age 38.7 years; college degree 59%; insulin pump 62%. Actual use of NG was reported by 46% of AwD and 43% of CGs. A total of 45 concepts were identified, the majority (81%) identified by the first 5 interviews; saturation (the point at which no new concepts emerge) reached at 25 interviews. The most frequently stated concepts were: feeling safe having NG on hand (93%) ; ease of use for others (90%) ; comfort in having NG as a rescue treatment option (90%) ; confidence in others’ ability to use NG (86%) ; ease of instruction to others (86%) (Figure) . These firsthand experiences give useful clinical insights regarding NG, deepening our understanding for practice considerations.

Disclosure
B.Mitchell: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. F.G.Sowell: None. P.Williams: None. J.Poon: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company.

Funding
Eli Lilly and Company
386-P: ROCK1 Regulation of AMPK in the Development of Diabetic Nephropathy
Authors: NAGAI YOSUKE , MATOBA KEIICHIRO , SEKIGUCHI KENSUKE , TAKEDA YUSUKE , KANAZAWA YASUSHI , KAWANAMI DAIJI , UTSUNOMIYA KAZUNORI , NISHIMURA RIMEI 
Published: May 2022

Rho-associated, coiled-coil-containing protein kinase (ROCK) is activated in the diabetic kidney. Studies over the past decade have illuminated ROCK signaling as an essential pathway in the pathogenesis of diabetic nephropathy. Accumulating evidence shows that renal dysfunction among patient with diabetes is associated with abnormal fatty acid oxidation in the kidney. However, the interaction of ROCK and fatty acid oxidation in diabetic kidneys remains unclear. Extracellular flux analyzer demonstrated that deficiency of ROCK1, one of the ROCK isoforms, improves TGF-β-induced mitochondrial dysfunction in primary cultured mesangial cells. ROCK1 deficiency rescued TGF-β-induced downregulation of fatty acid oxidation mediators such as peroxisome proliferator-activated receptor gamma coactivator 1-α (PGC-1α) , and carnitine palmitoyltransferase 1A (CPT1A) . An investigation of mechanisms underlying this observation revealed activated ROCK1 axis through the phosphorylation of AMPK and increased expression of PGC-1α. Fluorescence histochemistry showed that ROCK1 deficiency suppresses ROS production induced by mitochondrial damage due to abnormal fatty acid metabolism. Consistent with this result, compared to wild-type mice, ROCK1 knockout mice exhibited reduced albuminuria and histological abnormalities along with the recovery of impaired fatty acid utilization and mitochondrial fragmentation. Furthermore, RNA-seq showed that ROCK1 deficiency in mesangial cells significantly altered the expression of genes involved in metabolic pathway. These observations indicate that ROCK1 is a key player in the development of diabetic renal injury. ROCK1 may be a potential therapeutic target for the treatment of diabetic nephropathy.

Disclosure
Y.Nagai: None. K.Matoba: None. K.Sekiguchi: None. Y.Takeda: None. Y.Kanazawa: None. D.Kawanami: None. K.Utsunomiya: None. R.Nishimura: Speaker's Bureau; Abbott Diabetes, Astellas Pharma Inc., AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Medtronic, Merck & Co., Inc., Novo Nordisk, Ono Pharmaceutical Co., Ltd., Sanofi, Taisho Pharmaceutical Holdings Co., Ltd., Takeda Pharmaceutical Company Limited, Teijin Pharma Limited, Terumo Corporation.
403-P: Reduced Mitochondrial DNA Copy Number in Type 1 Diabetes and Nephropathy and Correlates Thereof
Authors: JANUSZEWSKI ANDRZEJ S. , CARROLL LUKE , LOH YIK W. , O'NEAL DAVID N. , JENKINS ALICIA 
Published: May 2022

Background: Mitochondrial DNA (Mt-DNA) copy number (mtDNA-CN) has been proposed as a marker of diabetic kidney disease (DKD) . Most studies are in type 2 diabetes. We determined mtDNA-CN in adults with type 1 diabetes vs. non-diabetic subjects, including associations with complications and risk factors.
Methods: Cross-sectional study: 178 T1D adults (mean (SD) age: 38 (14) yrs, 21 (14) yrs T1D, HbA1c: 8.0 (1.5) %, 36% with complications (CX+)) ; 132 non-diabetic adults (CON) (age: 37 (14) yrs, HbA1c: 5.1 (0.4) %) . mtDNA-CN by RT-PCR (ScienCell, Carlsbad, CA) in DNA from whole blood samples.
Results: T1D vs. CON: Median (LQ, UQ) mtDNA-CN in T1D vs. CON: 270.8 (189.4, 348.1) vs. 320.5 (264.4, 410.5) ; p&lt;0.0001. mtDNA-CN was lower in T1D with vs. without DKD (238.2 (179.6, 309.1) vs. 293.7 (197.6, 364.4) ; p=0.02, but did not differ by retinopathy or macrovascular disease. T1D mtDNA-CN tertiles: The highest tertile had lowest CX rate (25% (tertile 3) vs. 41% (tertiles 1+2) , p=0.03. Detectable C-peptide rates increased with higher mtDNA-CN tertiles (55%, 69%, 79%, p=0.02) . There were no differences by sex, smoking, BMI status, metabolic syndrome, HbA1c, exercise, statins or ACE/ARB. Correlates of mtDNA-CN: In T1D: FBG (r=-0.19, p=0.02) , HDL-C (r=0.17, p=0.03) , WCC (r=-0.16, p=0.04) , sVCAM-1 (r=-0.17, p=0.03) and sICAM-1 (r=-0.20, p=0.02) . In CON: WHR (r=-0.22, p=0.03) ; WCC (r=-0.24, p=0.007) . Independent determinants of mtDNA-CN: In T1D: age (-0.25±0.10; p=0.02) , HDL-C (0.27±0.10; p=0.007) , sICAM-1 (-0.42±0.12; p=0.001) . Area under ROC curve 0.72. In CON: pulse pressure (0.25±013; p=0.047) , WCC (-0.41±0.15; p=0.005) , smoking status (never) (0.22±0.13; p=0.09) ; sex (female) (0.35±0.12; p=0.005) . Area under ROC curve 0.74.
Conclusion: T1D per se is associated with lower mtDNA-CN than CON, particularly with DKD. Higher mtDNA-CN in T1D is associated with detectable C-peptide. Age and inflammation related factors are associated with mtDNA-CN. Longitudinal and intervention studies are merited.

Disclosure
A.S.Januszewski: None. L.Carroll: None. Y.W.Loh: None. D.N.O'neal: None. A.Jenkins: Advisory Panel; Abbott Diabetes, Amgen Inc., Board Member; Insulin for Life , International Diabetes Federation Western Pacific Region, Research Support; JDRF, Medtronic, Mylan N.V., NHMRC Australia.
409-P: Long-Term Testosterone Treatment Improves Estimated Glomerular Filtration Rate (eGFR) in Men with Hypogonadism and Type 2 Diabetes Mellitus: Update of Registry Data
Authors: HAIDER KARIM S. , HAIDER AHMAD , SAAD FARID 
Published: May 2022

Background: Reduced eGFR is associated with increased risk of cardiovascular disease and mortality.
Methods: Of 370 men with hypogonadism and T2DM, 190 received testosterone undecanoate 1000 mg/12 weeks (T-group) , 180 opted against treatment (CTRL) . Means and standard deviations of absolute measures over 13 years are reported. eGFR was calculated using the MDRD and the CKD-EPI formula.
Results: Mean baseline age: 62.0±5.2, mean (median) follow-up: 9.3±3.1 (10) years. Creatinine (mg/dL) decreased from 0.95±0.15 to 0.81±0.in the T-group and increased from 1.00±0.14 to 1.27±0.22 in CTRL (p&lt;0.00for both) .
Systolic blood pressure (mmHg) decreased in the T-group from 163.0±13.3 to 129.8±6.5 and increased in CTRL from 145.5±14.5 to 162.9±13.1 (p&lt;0.00for both) .
Diastolic blood pressure decreased in the T-group from 97.3±10.7 to 74.8±3.1 and increased in CTRL from 84.7±10.2 to 96.8±7.5 (p&lt;0.00for both) .
T-group: eGFR (MDRD) (mL/min/1.73 m²) increased from 82.5±12.8 to 94.4±9.1. CTRL: eGFR decreased from 77.2±12.1 to 56.9±10.6) (p&lt;0.00for both) .
T-group: eGFR (CKD-EPI) (mL/min/1.73 m²) increased from 84.0±15.4 to 87.5±4.7. CTRL: eGFR decreased from 77.0±13.9 to 49.8±12.3) (p&lt;0.00for both) .
21 deaths (11.1%) and no cardiovascular events occurred in the T-group. In CTRL, 62 deaths (34.4%) , 62 myocardial infarctions (34.4%) and 51 strokes (28.3%) were recorded (p&lt;0.00for all) . Nephropathy occurred in 1 man (0.01%) in the T-group and in 7 (0.4%) in CTRL (p=0.05) .
Conclusions: Long-term testosterone therapy in men with hypogonadism and T2DM prevents age-related deterioration in GFR.

Disclosure
K.S.Haider: Other Relationship; Bayer AG. A.Haider: Other Relationship; Bayer AG. F.Saad: Consultant; Bayer AG, Stock/Shareholder; AbbVie Inc., Bayer AG, GlaxoSmithKline plc.

Funding
Bayer AG