Browsing by Author "Sherr, Jennifer L."

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    Changes in Device Uptake and Glycemic Control Among Pregnant Women With Type 1 Diabetes: Data From the T1D Exchange
    (Sage, 2021) Levy, Carol J.; Foster, Nicole C.; DuBose, Stephanie N.; Agarwal, Shivani; Lyons, Sarah K.; Peters, Anne L.; Uwaifo, Gabriel I.; DiMeglio, Linda A.; Sherr, Jennifer L.; Polsky, Sarit; Pediatrics, School of Medicine
    Objectives: To examine changes in device use and glycemic outcomes for pregnant women from the T1D Exchange Clinic Registry between the years 2010-2013 and 2016-2018. Methods: Participant-reported device use and glycemic outcomes were compared for women aged 16-40 years who were pregnant at the time of survey completion, comparing 2010-2013 (cohort 1) and 2016-2018 (cohort 2). Hemoglobin A1c results within 30 days prior to survey completion were obtained from medical records. Results: There were 208 pregnant women out of 5,236 eligible participants completing the questionnaire in cohort 1 and 47 pregnant women out of 2,818 eligible participants completing the questionaire in cohort 2. Continuous glucose monitor (CGM) use while pregnant trended upward among cohort 2 (70% vs 37%, P = .02), while reported continuous subcutaneous insulin infusion (CSII) use while pregnant declined (76% vs 64%, P = .04). HbA1c levels trended downward (6.8% cohort 1 vs 6.5% cohort 2, P = .07). Conclusions: Self-reported CGM use while pregnant increased over the studied intervals whereas CSII use decreased. Additional evaluation of device use and the potential benefits for T1D pregnancies is needed.
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    Consensus Report on Glucagon-Like Peptide-1 Receptor Agonists as Adjunctive Treatment for Individuals With Type 1 Diabetes Using an Automated Insulin Delivery System
    (Sage, 2024-11-08) Shah, Viral N.; Peters, Anne L.; Umpierrez, Guillermo E.; Sherr, Jennifer L.; Akturk, Halis Kaan; Aleppo, Grazia; Bally, Lia; Cengiz, Eda; Cinar, Ali; Dungan, Kathleen; Fabris, Chiara; Jacobs, Peter G.; Lal, Rayhan A.; Mader, Julia K.; Masharani, Umesh; Prahalad, Priya; Schmidt, Signe; Zijlstra, Eric; Ho, Cindy N.; Ayers, Alessandra T.; Tian, Tiffany; Aaron, Rachel E.; Klonoff, David C.; Medicine, School of Medicine
    With increasing prevalence of obesity and cardiovascular diseases, there is a growing interest in the use of glucagon-like peptide-1 receptor agonists (GLP-1RAs) as an adjunct therapy in type 1 diabetes (T1D). The GLP-1RAs are currently not approved by the US Food and Drug Administration for the treatment of T1D in the absence of randomized controlled trials documenting efficacy and safety of these agents in this population. The Diabetes Technology Society convened a series of three consensus meetings of clinicians and researchers with expertise in diabetes technology, GLP-1RA therapy, and T1D management. The project was aimed at synthesizing current literature and providing conclusions on the use of GLP-1RA therapy as an adjunct to automated insulin delivery (AID) systems in adults with T1D. The expert panel members met virtually three times on January 17, 2024, and April 24, 2024, and August 14, 2024, to discuss topics ranging from physiology and outcomes of GLP-1RAs in T1D to limitations of current sensors, algorithms, and insulin for AID systems. The panelists also identified research gaps and future directions for research. The panelists voted to in favor of 31 recommendations. This report presents the consensus opinions of the participants that, in adults with T1D using AID systems, GLP-1RAs have the potential to (1) provide effective adjunct therapy and (2) improve glycemic and metabolic outcomes without increasing the risk of severe hypoglycemia or diabetic ketoacidosis.
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    Effect of Tight Glycemic Control on Pancreatic Beta Cell Function in Newly Diagnosed Pediatric Type 1 Diabetes: A Randomized Clinical Trial
    (American Medical Association, 2023) McVean, Jennifer; Forlenza, Gregory P.; Beck, Roy W.; Bauza, Colleen; Bailey, Ryan; Buckingham, Bruce; DiMeglio, Linda A.; Sherr, Jennifer L.; Clements, Mark; Neyman, Anna; Evans-Molina, Carmella; Sims, Emily K.; Messer, Laurel H.; Ekhlaspour, Laya; McDonough, Ryan; Van Name, Michelle; Rojas, Diana; Beasley, Shannon; DuBose, Stephanie; Kollman, Craig; Moran, Antoinette; CLVer Study Group; Pediatrics, School of Medicine
    Importance: Near normalization of glucose levels instituted immediately after diagnosis of type 1 diabetes has been postulated to preserve pancreatic beta cell function by reducing glucotoxicity. Previous studies have been hampered by an inability to achieve tight glycemic goals. Objective: To determine the effectiveness of intensive diabetes management to achieve near normalization of glucose levels on preservation of pancreatic beta cell function in youth with newly diagnosed type 1 diabetes. Design, setting, and participants: This randomized, double-blind, clinical trial was conducted at 6 centers in the US (randomizations from July 20, 2020, to October 13, 2021; follow-up completed September 15, 2022) and included youths with newly diagnosed type 1 diabetes aged 7 to 17 years. Interventions: Random assignment to intensive diabetes management, which included use of an automated insulin delivery system (n = 61), or standard care, which included use of a continuous glucose monitor (n = 52), as part of a factorial design in which participants weighing 30 kg or more also were assigned to receive either oral verapamil or placebo. Main outcomes and measures: The primary outcome was mixed-meal tolerance test-stimulated C-peptide area under the curve (a measure of pancreatic beta cell function) 52 weeks from diagnosis. Results: Among 113 participants (mean [SD] age, 11.8 [2.8] years; 49 females [43%]; mean [SD] time from diagnosis to randomization, 24 [5] days), 108 (96%) completed the trial. The mean C-peptide area under the curve decreased from 0.57 pmol/mL at baseline to 0.45 pmol/mL at 52 weeks in the intensive management group, and from 0.60 to 0.50 pmol/mL in the standard care group (treatment group difference, -0.01 [95% CI, -0.11 to 0.10]; P = .89). The mean time in the target range of 70 to 180 mg/dL, measured with continuous glucose monitoring, at 52 weeks was 78% in the intensive management group vs 64% in the standard care group (adjusted difference, 16% [95% CI, 10% to 22%]). One severe hypoglycemia event and 1 diabetic ketoacidosis event occurred in each group. Conclusions and relevance: In youths with newly diagnosed type 1 diabetes, intensive diabetes management, which included automated insulin delivery, achieved excellent glucose control but did not affect the decline in pancreatic C-peptide secretion at 52 weeks.
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    Effect of Verapamil on Pancreatic Beta Cell Function in Newly Diagnosed Pediatric Type 1 Diabetes: A Randomized Clinical Trial
    (American Medical Association, 2023) Forlenza, Gregory P.; McVean, Jennifer; Beck, Roy W.; Bauza, Colleen; Bailey, Ryan; Buckingham, Bruce; DiMeglio, Linda A.; Sherr, Jennifer L.; Clements, Mark; Neyman, Anna; Evans-Molina, Carmella; Sims, Emily K.; Messer, Laurel H.; Ekhlaspour, Laya; McDonough, Ryan; Van Name, Michelle; Rojas, Diana; Beasley, Shannon; DuBose, Stephanie; Kollman, Craig; Moran, Antoinette; CLVer Study Group; Pediatrics, School of Medicine
    Importance: In preclinical studies, thioredoxin-interacting protein overexpression induces pancreatic beta cell apoptosis and is involved in glucotoxicity-induced beta cell death. Calcium channel blockers reduce these effects and may be beneficial to beta cell preservation in type 1 diabetes. Objective: To determine the effect of verapamil on pancreatic beta cell function in children and adolescents with newly diagnosed type 1 diabetes. Design, setting, and participants: This double-blind, randomized clinical trial including children and adolescents aged 7 to 17 years with newly diagnosed type 1 diabetes who weighed 30 kg or greater was conducted at 6 centers in the US (randomized participants between July 20, 2020, and October 13, 2021) and follow-up was completed on September 15, 2022. Interventions: Participants were randomly assigned 1:1 to once-daily oral verapamil (n = 47) or placebo (n = 41) as part of a factorial design in which participants also were assigned to receive either intensive diabetes management or standard diabetes care. Main outcomes and measures: The primary outcome was area under the curve values for C-peptide level (a measure of pancreatic beta cell function) stimulated by a mixed-meal tolerance test at 52 weeks from diagnosis of type 1 diabetes. Results: Among 88 participants (mean age, 12.7 [SD, 2.4] years; 36 were female [41%]; and the mean time from diagnosis to randomization was 24 [SD, 4] days), 83 (94%) completed the trial. In the verapamil group, the mean C-peptide area under the curve was 0.66 pmol/mL at baseline and 0.65 pmol/mL at 52 weeks compared with 0.60 pmol/mL at baseline and 0.44 pmol/mL at 52 weeks in the placebo group (adjusted between-group difference, 0.14 pmol/mL [95% CI, 0.01 to 0.27 pmol/mL]; P = .04). This equates to a 30% higher C-peptide level at 52 weeks with verapamil. The percentage of participants with a 52-week peak C-peptide level of 0.2 pmol/mL or greater was 95% (41 of 43 participants) in the verapamil group vs 71% (27 of 38 participants) in the placebo group. At 52 weeks, hemoglobin A1c was 6.6% in the verapamil group vs 6.9% in the placebo group (adjusted between-group difference, -0.3% [95% CI, -1.0% to 0.4%]). Eight participants (17%) in the verapamil group and 8 participants (20%) in the placebo group had a nonserious adverse event considered to be related to treatment. Conclusions and relevance: In children and adolescents with newly diagnosed type 1 diabetes, verapamil partially preserved stimulated C-peptide secretion at 52 weeks from diagnosis compared with placebo. Further studies are needed to determine the longitudinal durability of C-peptide improvement and the optimal length of therapy.
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    Gender differences in diabetes self-care in adults with type 1 diabetes: Findings from the T1D Exchange clinic registry
    (Elsevier, 2018-10) Shah, Viral N.; Wu, Mengdi; Polsky, Sarit; Snell-Bergeon, Janet K.; Sherr, Jennifer L.; Cengiz, Eda; DiMeglio, Linda A.; Pop-Busui, Rodica; Mizokami-Stout, Kara; Foster, Nicole C.; Beck, Roy W.; Pediatrics, School of Medicine
    Aims To evaluate gender differences in diabetes self-care components including glycemic, blood pressure and lipid control, utilization of diabetes technologies and acute diabetes complications in adults with type 1 diabetes. Methods A total of 9,481 participants >18 years were included in the analysis, 53% were female. Variables of interest included glycemic control measured by HbA1c, systolic/diastolic blood pressures, presence of dyslipidemia, insulin delivery modality, and rates of acute complications. Results Glycemic control was similar in women and men (mean HbA1c in both groups: 8.1% ± 1.6% (64 ± 16 mmol/mol), (p = 0.54). More women used insulin pump therapy (66% vs. 59%, p < 0.001) but use of sensor technology was similar (p < = 0.42). Women had higher rates of diabetic ketoacidosis (DKA) (5% vs. 3%, p < 0.001) and eating disorders (1.7% vs. 0.1%, p < 0.001). Severe hypoglycemia rates were not different between men and women (p = 0.42). Smoking (6% vs 4%, p < 0.001), systolic (125 ± 14.2 vs. 121 ± 14.4, p < 0.001) and diastolic blood pressure (73.3 ± 9.5 vs. 72.2 ± 9.3, p < 0.001) and rate of dyslipidemia (28% vs. 23%, p < 0.001) were higher in men. Conclusion While glycemic control in type 1 diabetes was similar regardless of gender, rates of DKA and eating disorders were higher in women while rates of smoking, hypertension and dyslipidemia were higher in men.
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    High residual C-peptide likely contributes to glycemic control in type 1 diabetes
    (American Society for Clinical Investigation, 2020-01-02) Rickels, Michael R.; Evans-Molina, Carmella; Bahnson, Henry T.; Ylescupidez, Alyssa; Nadeau, Kristen J.; Hao, Wei; Clements, Mark A.; Sherr, Jennifer L.; Pratley, Richard E.; Hannon, Tamara S.; Shah, Viral N.; Miller, Kellee M.; Greenbaum, Carla J.; Medicine, School of Medicine
    BACKGROUND Residual C-peptide is detected in many people for years following the diagnosis of type 1 diabetes; however, the physiologic significance of low levels of detectable C-peptide is not known. METHODS We studied 63 adults with type 1 diabetes classified by peak mixed-meal tolerance test (MMTT) C-peptide as negative (<0.007 pmol/mL; n = 15), low (0.017–0.200; n = 16), intermediate (>0.200–0.400; n = 15), or high (>0.400; n = 17). We compared the groups’ glycemia from continuous glucose monitoring (CGM), β cell secretory responses from a glucose-potentiated arginine (GPA) test, insulin sensitivity from a hyperinsulinemic-euglycemic (EU) clamp, and glucose counterregulatory responses from a subsequent hypoglycemic (HYPO) clamp. RESULTS Low and intermediate MMTT C-peptide groups did not exhibit β cell secretory responses to hyperglycemia, whereas the high C-peptide group showed increases in both C-peptide and proinsulin (P ≤ 0.01). All groups with detectable MMTT C-peptide demonstrated acute C-peptide and proinsulin responses to arginine that were positively correlated with peak MMTT C-peptide (P < 0.0001 for both analytes). During the EU-HYPO clamp, C-peptide levels were proportionately suppressed in the low, intermediate, and high C-peptide compared with the negative group (P ≤ 0.0001), whereas glucagon increased from EU to HYPO only in the high C-peptide group compared with negative (P = 0.01). CGM demonstrated lower mean glucose and more time in range for the high C-peptide group. CONCLUSION These results indicate that in adults with type 1 diabetes, β cell responsiveness to hyperglycemia and α cell responsiveness to hypoglycemia are observed only at high levels of residual C-peptide that likely contribute to glycemic control. FUNDING Funding for this work was provided by the Leona M. and Harry B. Helmsley Charitable Trust, the National Center for Advancing Translational Sciences, and the National Institute of Diabetes and Digestive and Kidney Diseases.
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    Incident Diabetes Complications among Women with type 1 diabetes based on Parity
    (Taylor & Francis, 2020) Polsky, Sarit; Foster, Nicole C.; DuBose, Stephanie N.; Agarwal, Shivani; Lyons, Sarah; Peters, Anne L.; Uwaifo, Gabriel I.; DiMeglio, Linda A.; Sherr, Jennifer L.; Levy, Carol J.; Pediatrics, School of Medicine
    Objectives To assess risk factors and incidence of diabetes complications in women with type 1 diabetes (T1D) based on parity. Research design/methods Data were collected from women (16–40 years old) in the T1D Exchange completing pregnancy/childbirth questionnaires during 2011–2013 and 2016–2018. Incidence of risk factors and diabetes complications were compared between women with a first pregnancy at/within 1-year of enrollment (n = 28) and never pregnant women by year 5 (n = 469). Results There was a trend for lower HbA1c (adjusted p = .14) and higher rates of overweight/obesity, triglyceride/HDL > 2, log (triglyercide/HDL), and hypertension among parous women compared with nulliparous women. There were no significant differences in rates of advanced nephropathy, albuminuria or cardiovascular disease. Conclusions Four-5 years after delivery, parous women with T1D tended to have lower HbA1c levels despite higher body mass indices and more frequent adverse lipid profiles and hypertension compared with nulliparous women. Further studies based on these trends are warranted.
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    Safety and prescribing recommendations for verapamil in newly diagnosed pediatric type 1 diabetes (T1D): The CLVer experience
    (Elsevier, 2024-05-18) Ekhlaspour, Laya; Buckingham, Bruce; Bauza, Colleen; Clements, Mark; Forlenza, Gregory P.; Neyman, Anna; Norlander, Lisa; Schamberger, Marcus; Sherr, Jennifer L.; Bailey, Ryan; Beck, Roy W.; Kollman, Craig; Beasley, Shannon; Cobry, Erin; DiMeglio, Linda A.; Paprocki, Emily; Van Name, Michelle; Moran, Antoinette; CLVer Study Group; Pediatrics, School of Medicine
    Objectives: To report the safety and side effects associated with taking verapamil for beta-cell preservation in children with newly-diagnosed T1D. Research design and methods: Eighty-eight participants aged 8.5 to 17.9 years weighing ≥ 30 kg were randomly assigned to verapamil (N = 47) or placebo (N = 41) within 31 days of T1D diagnosis and followed for 12 months from diagnosis, main CLVer study. Drug dosing was weight-based with incremental increases to full dosage. Side effect monitoring included serial measurements of pulse, blood pressure, liver enzymes, and electrocardiograms (ECGs). At study end, participants were enrolled in an observational extension study (CLVerEx), which is ongoing. No study drug is provided during the extension, but participants may use verapamil if prescribed by their diabetes care team. Results: Overall rates of adverse events were low and comparable between verapamil and placebo groups. There was no difference in the frequency of liver function abnormalities. Three CLVer participants reduced or discontinued medication due to asymptomatic ECG changes. One CLVerEx participant (18 years old), treated with placebo during CLVer, who had not had a monitoring ECG, experienced complete AV block with a severe hypotensive episode 6 weeks after reaching his maximum verapamil dose following an inadvertent double dose on the day of the event. Conclusions: The use of verapamil in youth newly-diagnosed with T1D appears generally safe and well tolerated with appropriate monitoring. We strongly recommend monitoring for potential side effects including an ECG at screening and an additional ECG once full dosage is reached.
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    Second international consensus report on gaps and opportunities for the clinical translation of precision diabetes medicine
    (Springer Nature, 2023) Tobias, Deirdre K.; Merino, Jordi; Ahmad, Abrar; Aiken, Catherine; Benham, Jamie L.; Bodhini, Dhanasekaran; Clark, Amy L.; Colclough, Kevin; Corcoy, Rosa; Cromer, Sara J.; Duan, Daisy; Felton, Jamie L.; Francis, Ellen C.; Gillard, Pieter; Gingras, Véronique; Gaillard, Romy; Haider, Eram; Hughes, Alice; Ikle, Jennifer M.; Jacobsen, Laura M.; Kahkoska, Anna R.; Kettunen, Jarno L. T.; Kreienkamp, Raymond J.; Lim, Lee-Ling; Männistö, Jonna M. E.; Massey, Robert; Mclennan, Niamh-Maire; Miller, Rachel G.; Morieri, Mario Luca; Most, Jasper; Naylor, Rochelle N.; Ozkan, Bige; Patel, Kashyap Amratlal; Pilla, Scott J.; Prystupa, Katsiaryna; Raghavan, Sridharan; Rooney, Mary R.; Schön, Martin; Semnani-Azad, Zhila; Sevilla-Gonzalez, Magdalena; Svalastoga, Pernille; Takele, Wubet Worku; Tam, Claudia Ha-Ting; Thuesen, Anne Cathrine B.; Tosur, Mustafa; Wallace, Amelia S.; Wang, Caroline C.; Wong, Jessie J.; Yamamoto, Jennifer M.; Young, Katherine; Amouyal, Chloé; Andersen, Mette K.; Bonham, Maxine P.; Chen, Mingling; Cheng, Feifei; Chikowore, Tinashe; Chivers, Sian C.; Clemmensen, Christoffer; Dabelea, Dana; Dawed, Adem Y.; Deutsch, Aaron J.; Dickens, Laura T.; DiMeglio, Linda A.; Dudenhöffer-Pfeifer, Monika; Evans-Molina, Carmella; Fernández-Balsells, María Mercè; Fitipaldi, Hugo; Fitzpatrick, Stephanie L.; Gitelman, Stephen E.; Goodarzi, Mark O.; Grieger, Jessica A.; Guasch-Ferré, Marta; Habibi, Nahal; Hansen, Torben; Huang, Chuiguo; Harris-Kawano, Arianna; Ismail, Heba M.; Hoag, Benjamin; Johnson, Randi K.; Jones, Angus G.; Koivula, Robert W.; Leong, Aaron; Leung, Gloria K. W.; Libman, Ingrid M.; Liu, Kai; Long, S. Alice; Lowe, William L., Jr.; Morton, Robert W.; Motala, Ayesha A.; Onengut-Gumuscu, Suna; Pankow, James S.; Pathirana, Maleesa; Pazmino, Sofia; Perez, Dianna; Petrie, John R.; Powe, Camille E.; Quinteros, Alejandra; Jain, Rashmi; Ray, Debashree; Ried-Larsen, Mathias; Saeed, Zeb; Santhakumar, Vanessa; Kanbour, Sarah; Sarkar, Sudipa; Monaco, Gabriela S. F.; Scholtens, Denise M.; Selvin, Elizabeth; Sheu, Wayne Huey-Herng; Speake, Cate; Stanislawski, Maggie A.; Steenackers, Nele; Steck, Andrea K.; Stefan, Norbert; Støy, Julie; Taylor, Rachael; Tye, Sok Cin; Ukke, Gebresilasea Gendisha; Urazbayeva, Marzhan; Van der Schueren, Bart; Vatier, Camille; Wentworth, John M.; Hannah, Wesley; White, Sara L.; Yu, Gechang; Zhang, Yingchai; Zhou, Shao J.; Beltrand, Jacques; Polak, Michel; Aukrust, Ingvild; de Franco, Elisa; Flanagan, Sarah E.; Maloney, Kristin A.; McGovern, Andrew; Molnes, Janne; Nakabuye, Mariam; Njølstad, Pål Rasmus; Pomares-Millan, Hugo; Provenzano, Michele; Saint-Martin, Cécile; Zhang, Cuilin; Zhu, Yeyi; Auh, Sungyoung; de Souza, Russell; Fawcett, Andrea J.; Gruber, Chandra; Mekonnen, Eskedar Getie; Mixter, Emily; Sherifali, Diana; Eckel, Robert H.; Nolan, John J.; Philipson, Louis H.; Brown, Rebecca J.; Billings, Liana K.; Boyle, Kristen; Costacou, Tina; Dennis, John M.; Florez, Jose C.; Gloyn, Anna L.; Gomez, Maria F.; Gottlieb, Peter A.; Greeley, Siri Atma W.; Griffin, Kurt; Hattersley, Andrew T.; Hirsch, Irl B.; Hivert, Marie-France; Hood, Korey K.; Josefson, Jami L.; Kwak, Soo Heon; Laffel, Lori M.; Lim, Siew S.; Loos, Ruth J. F.; Ma, Ronald C. W.; Mathieu, Chantal; Mathioudakis, Nestoras; Meigs, James B.; Misra, Shivani; Mohan, Viswanathan; Murphy, Rinki; Oram, Richard; Owen, Katharine R.; Ozanne, Susan E.; Pearson, Ewan R.; Perng, Wei; Pollin, Toni I.; Pop-Busui, Rodica; Pratley, Richard E.; Redman, Leanne M.; Redondo, Maria J.; Reynolds, Rebecca M.; Semple, Robert K.; Sherr, Jennifer L.; Sims, Emily K.; Sweeting, Arianne; Tuomi, Tiinamaija; Udler, Miriam S.; Vesco, Kimberly K.; Vilsbøll, Tina; Wagner, Robert; Rich, Stephen S.; Franks, Paul W.; Pediatrics, School of Medicine
    Precision medicine is part of the logical evolution of contemporary evidence-based medicine that seeks to reduce errors and optimize outcomes when making medical decisions and health recommendations. Diabetes affects hundreds of millions of people worldwide, many of whom will develop life-threatening complications and die prematurely. Precision medicine can potentially address this enormous problem by accounting for heterogeneity in the etiology, clinical presentation and pathogenesis of common forms of diabetes and risks of complications. This second international consensus report on precision diabetes medicine summarizes the findings from a systematic evidence review across the key pillars of precision medicine (prevention, diagnosis, treatment, prognosis) in four recognized forms of diabetes (monogenic, gestational, type 1, type 2). These reviews address key questions about the translation of precision medicine research into practice. Although not complete, owing to the vast literature on this topic, they revealed opportunities for the immediate or near-term clinical implementation of precision diabetes medicine; furthermore, we expose important gaps in knowledge, focusing on the need to obtain new clinically relevant evidence. Gaps include the need for common standards for clinical readiness, including consideration of cost-effectiveness, health equity, predictive accuracy, liability and accessibility. Key milestones are outlined for the broad clinical implementation of precision diabetes medicine.