المؤلفون: Faggionato, Edoardo, Schiavon, Michele, Ekhlaspour, Laya, Buckingham, Bruce, Dalla Man, Chiara

المصدر: IEEE Transactions on Biomedical Engineering. 71(3)

مصطلحات موضوعية: Humans, Adult, Middle Aged, Glucose, Diabetes Mellitus, Type 1, Insulin Resistance, Blood Glucose, Blood Glucose Self-Monitoring, Bayes Theorem, Insulin, Hypoglycemic Agents

الوصف: OBJECTIVE: Modeling the effect of meal composition on glucose excursion would help in designing decision support systems (DSS) for type 1 diabetes (T1D) management. In fact, macronutrients differently affect post-prandial gastric retention (GR), rate of appearance (R[Formula: see text]), and insulin sensitivity (S[Formula: see text]). Such variables can be estimated, in inpatient settings, from plasma glucose (G) and insulin (I) data using the Oral glucose Minimal Model (OMM) coupled with a physiological model of glucose transit through the gastrointestinal tract (reference OMM, R-OMM). Here, we present a model able to estimate those quantities in daily-life conditions, using minimally-invasive (MI) technologies, and validate it against the R-OMM. METHODS: Forty-seven individuals with T1D (weight =78±13 kg, age =42±10 yr) underwent three 23-hour visits, during which G and I were frequently sampled while wearing continuous glucose monitoring (CGM) and insulin pump (IP). Using a Bayesian Maximum A Posteriori estimator, R-OMM was identified from plasma G and I measurements, and MI-OMM was identified from CGM and IP data. RESULTS: The MI-OMM fitted the CGM data well and provided precise parameter estimates. GR and R[Formula: see text] model parameters were not significantly different using the MI-OMM and R-OMM (p 0.05) and the correlation between the two S[Formula: see text] was satisfactory ( ρ =0.77). CONCLUSION: The MI-OMM is usable to estimate GR, R[Formula: see text], and S[Formula: see text] from data collected in real-life conditions with minimally-invasive technologies. SIGNIFICANCE: Applying MI-OMM to datasets where meal compositions are available will allow modeling the effect of each macronutrient on GR, R[Formula: see text], and S[Formula: see text]. DSS could finally exploit this information to improve diabetes management.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/4zm3c05sTest

المؤلفون: Loomba, Rohit, Abdelmalek, Manal F, Armstrong, Matthew J, Jara, Maximilian, Kjær, Mette Skalshøi, Krarup, Niels, Lawitz, Eric, Ratziu, Vlad, Sanyal, Arun J, Schattenberg, Jörn M, Newsome, Philip N, investigators, NN9931-4492

المصدر: The Lancet Gastroenterology & Hepatology. 8(6)

مصطلحات موضوعية: Biomedical and Clinical Sciences, Clinical Sciences, Clinical Research, Chronic Liver Disease and Cirrhosis, Hepatitis, Liver Disease, Digestive Diseases, Clinical Trials and Supportive Activities, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Good Health and Well Being, Adult, Humans, Male, Female, Middle Aged, Diabetes Mellitus, Type 2, Non-alcoholic Fatty Liver Disease, Glucagon-Like Peptide 1, Liver Cirrhosis, NN9931-4492 investigators, Clinical sciences

الوصف: BackgroundPatients with non-alcoholic steatohepatitis (NASH)-related cirrhosis are at high risk of liver-related and all-cause morbidity and mortality. We investigated the efficacy and safety of the glucagon-like peptide-1 analogue semaglutide in patients with NASH and compensated cirrhosis.MethodsThis double-blind, placebo-controlled phase 2 trial enrolled patients from 38 centres in Europe and the USA. Adults with biopsy-confirmed NASH-related cirrhosis and body-mass index (BMI) of 27 kg/m2 or more were randomly assigned (2:1) to receive either once-weekly subcutaneous semaglutide 2·4 mg or visually matching placebo. Patients were randomly allocated via an interactive web response system, stratified by presence or absence of type 2 diabetes. Patients, investigators, and those assessing outcomes were masked to treatment assignment. The primary endpoint was the proportion of patients with an improvement in liver fibrosis of one stage or more without worsening of NASH after 48 weeks, assessed by biopsy in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of study drug. The trial is closed and completed, and registered with ClinicalTrials.gov, number NCT03987451.Findings71 patients were enrolled between June 18, 2019, and April 22, 2021; 49 (69%) patients were female and 22 (31%) were male. Patients had a mean age of 59·5 years (SD 8·0) and mean BMI of 34·9 kg/m2 (SD 5·9); 53 (75%) patients had diabetes. 47 patients were randomly assigned to the semaglutide group and 24 to the placebo group. After 48 weeks, there was no statistically significant difference between the two groups in the proportion of patients with an improvement in liver fibrosis of one stage or more without worsening of NASH (five [11%] of 47 patients in the semaglutide group vs seven [29%] of 24 in the placebo group; odds ratio 0·28 [95% CI 0·06-1·24; p=0·087). There was also no significant difference between groups in the proportion of patients who achieved NASH resolution (p=0·29). Similar proportions of patients in each group reported adverse events (42 [89%] patients in the semaglutide group vs 19 [79%] in the placebo group) and serious adverse events (six [13%] vs two [8%]). The most common adverse events were nausea (21 [45%] vs four [17%]), diarrhoea (nine [19%] vs two [8%]), and vomiting (eight [17%] vs none). Hepatic and renal function remained stable. There were no decompensating events or deaths.InterpretationIn patients with NASH and compensated cirrhosis, semaglutide did not significantly improve fibrosis or achievement of NASH resolution versus placebo. No new safety concerns were raised.FundingNovo Nordisk A/S.

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الوصول الحر: https://escholarship.org/uc/item/9z54p6grTest

المؤلفون: Isaacs, Dayna, Drakaki, Alexandra, Xing, Yan, In, Gino, Angell, Trevor, Lechner, Melissa, Hilder, Robin, Tsai, Karen, Quandt, Zoe

مصطلحات موضوعية: autoimmune endocrinopathy, immune checkpoint inhibitor, immune related adverse events, safety, type 1 diabetes mellitus, Adult, Humans, Female, Middle Aged, Male, Immune Checkpoint Inhibitors, Diabetes Mellitus, Type 1, Retrospective Studies, Prospective Studies, Antineoplastic Agents, Immunological, Neoplasms, Autoimmune Diseases

الوصف: INTRODUCTION: Immune checkpoint inhibitors (ICI) produce dramatic tumor shrinkage and durable responses in many advanced malignancies, but their use is limited by the development of immune-related adverse events (IRAEs) that occur in up to 60% of patients and often affect endocrine organs. Concern for more severe IRAEs in patients with preexisting autoimmune diseases, including type 1 diabetes mellitus (T1DM), has led to the exclusion of such individuals from clinical trials of ICI therapy. As a result, little is known about the safety and efficacy of ICI in this population. Here, we report safety and treatments outcomes in ICI-treated patients with preexisting T1DM. METHODS: This retrospective case-controlled study evaluated adult patients with T1DM who received ICI therapy for solid malignancies from 2015 to 2021 at four academic medical centers. Patients with prior ICI therapy, bone marrow transplantation, or pregnancy were excluded. We collected data on demographics, cancer diagnosis and treatment, IRAE incidence and severity, and diabetes management. Controls were matched 2:1 by age, sex, cancer diagnosis, and ICI therapy class. RESULTS: Of 12,142 cancer patients treated with ICI therapy, we identified 11 with a preexisting confirmed diagnosis of T1DM prior to starting ICI therapy. Mean age was 50.6 years, 63.6% were women, and most received anti-PD1/PDL1 monotherapy (10/11) compared with combination therapy (1/11). Grade 3/4 IRAEs were seen in 3/11 subjects with preexisting T1DM and were hepatitis, myositis, and myasthenia gravis. All three cases had interruption of ICI therapy and administration of adjunct therapies, including steroids, IVIG, or mycophenolate mofetil with resolution of the IRAE. The odds of all-grade IRAEs and of severe IRAEs were comparable between cases and controls matched for age, sex, cancer type, and ICI therapy [OR 0.83 (95% CI 0.2-3.56), p = 0.81, and OR 1.69 (0.31-9.36), p = 0.55, respectively]. Overall survival was not different between patients with T1DM and controls (p = 0.54). No patients had hospitalizations for diabetes-related complications during therapy. DISCUSSION: These data suggest that ICI monotherapy can successfully be used in patients with preexisting T1DM, with IRAE rates comparable with individuals without preexisting T1DM. Larger, prospective studies of these potentially life-saving ICI therapies that include patients with preexisting autoimmunity are warranted.

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الوصول الحر: https://escholarship.org/uc/item/5tm4f86nTest

المؤلفون: Pinsker, Jordan, Dassau, Eyal, Deshpande, Sunil, Raghinaru, Dan, Buckingham, Bruce, Kudva, Yogish, Laffel, Lori, Levy, Carol, Church, Mei, Desrochers, Hannah, Ekhlaspour, Laya, Kaur, Ravinder, Levister, Camilla, Shi, Dawei, Lum, John, Kollman, Craig, Doyle, Francis

المصدر: Diabetes Technology and Therapeutics. 24(9)

مصطلحات موضوعية: Adaptation, Artificial pancreas, Automated insulin delivery, Glycemic control, Type 1 diabetes, Adult, Blood Glucose, Cross-Over Studies, Diabetes Mellitus, Type 1, Humans, Hypoglycemic Agents, Infant, Newborn, Insulin, Insulin Infusion Systems, Insulin, Regular, Human, Middle Aged, Outpatients, Young Adult

الوصف: Background: Automated insulin delivery (AID) systems have proven effective in increasing time-in-range during both clinical trials and real-world use. Further improvements in outcomes for single-hormone (insulin only) AID may be limited by suboptimal insulin delivery settings. Methods: Adults (≥18 years of age) with type 1 diabetes were randomized to either sensor-augmented pump (SAP) (inclusive of predictive low-glucose suspend) or adaptive zone model predictive control AID for 13 weeks, then crossed over to the other arm. Each week, the AID insulin delivery settings were sequentially and automatically updated by an adaptation system running on the study phone. Primary outcome was sensor glucose time-in-range 70-180 mg/dL, with noninferiority in percent time below 54 mg/dL as a hierarchical outcome. Results: Thirty-five participants completed the trial (mean age 39 ± 16 years, HbA1c at enrollment 6.9% ± 1.0%). Mean time-in-range 70-180 mg/dL was 66% with SAP versus 69% with AID (mean adjusted difference +2% [95% confidence interval: -1% to +6%], P = 0.22). Median time

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الوصول الحر: https://escholarship.org/uc/item/76x9t6n0Test

المؤلفون: Lake, Jordan E, Wang, Ruibin, Barrett, Benjamin W, Bowman, Emily, Hyatt, Ana N, Debroy, Paula, Candelario, Jury, Teplin, Linda, Bodnar, Kaitlin, McKay, Heather, Plankey, Michael, Brown, Todd T, Funderburg, Nicholas, Currier, Judith S

المصدر: AIDS. 36(13)

مصطلحات موضوعية: Biomedical and Clinical Sciences, Clinical Sciences, Clinical Research, Prevention, Cardiovascular, HIV/AIDS, Infectious Diseases, Good Health and Well Being, 1-Alkyl-2-acetylglycerophosphocholine Esterase, Adult, Biomarkers, Cardiovascular Diseases, Cohort Studies, Endothelins, Female, HIV Infections, Hormones, Humans, Inflammation, Interleukin-6, Interleukin-8, Lipopolysaccharide Receptors, Lipoproteins, LDL, Male, Middle Aged, P-Selectin, Plasminogen Activator Inhibitor 1, Receptor for Advanced Glycation End Products, von Willebrand Factor, cardiovascular biomarkers, feminizing hormonal therapy, HIV, trans women, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Virology, Biomedical and clinical sciences, Health sciences

الوصف: BackgroundFeminizing hormonal therapy (FHT) and HIV potentially alter cardiovascular disease (CVD) risk in transgender women (TW).MethodsTW were enrolled in Los Angeles, California and Houston, Texas and frequency-matched to Multicenter AIDS Cohort Study cisgender men (CM) on age, race, substance use, and abacavir use. Biomarkers of CVD risk and inflammation were assessed via ELISA. Wilcoxon rank sum and Fisher's exact tests compared TW and CM. Multivariable linear regression assessed factors associated with biomarker concentrations.ResultsTW (HIV+ n  = 75, HIV- n  = 47) and CM (HIV+ n  = 40, HIV- n  = 40) had mean age 43-45 years; TW/CM were 90%/91% non-Hispanic Black, Hispanic, or Multiracial, 26%/53% obese, and 34%/24% current smokers; 67% of TW were on FHT. Among people with HIV (PWH), TW had higher median extracellular newly-identified receptor for advanced glycation end-products (EN-RAGE), lipoprotein-associated phospholipase A2 (LpPLA2), oxidized low-density lipoprotein (oxLDL), soluble tumor necrosis factor receptor type (sTNFR) I/II, interleukin (IL)-8 and plasminogen activator inhibitor (PAI)-1, but lower soluble CD14, von Willebrand factor (vWF) and endothelin (ET)-1 levels than CM. Findings were similar for participants without HIV (all P

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الوصول الحر: https://escholarship.org/uc/item/7842k8nbTest

المؤلفون: Russell, Steven, Beck, Roy, Damiano, Edward, El-Khatib, Firas, Ruedy, Katrina, Balliro, Courtney, Li, Zoey, Calhoun, Peter, Wadwa, R, Buckingham, Bruce, Zhou, Keren, Daniels, Mark, Raskin, Philip, White, Perrin, Lynch, Jane, Pettus, Jeremy, Hirsch, Irl, Goland, Robin, Buse, John, Kruger, Davida, Mauras, Nelly, Muir, Andrew, McGill, Janet, Cogen, Fran, Weissberg-Benchell, Jill, Sherwood, Jordan, Castellanos, Luz, Hillard, Mallory, Tuffaha, Marwa, Putman, Melissa, Sands, Mollie, Forlenza, Gregory, Slover, Robert, Messer, Laurel, Cobry, Erin, Shah, Viral, Polsky, Sarit, Lal, Rayhan, Ekhlaspour, Laya, Hughes, Michael, Basina, Marina, Hatipoglu, Betul, Olansky, Leann, Bhangoo, Amrit, Forghani, Nikta, Kashmiri, Himala, Sutton, Francoise, Choudhary, Abha, Penn, Jimmy, Jafri, Rabab, Rayas, Maria, Escaname, Elia, Kerr, Catherine, Favela-Prezas, Ruby, Trikudanathan, Subbulaxmi, Williams, Kristen, Leibel, Natasha, Kirkman, M, Bergamo, Kate, Klein, Klara, Dostou, Jean, Machineni, Sriram, Young, Laura, Diner, Jamie, Bhan, Arti, Jones, J, Benson, Matthew, Bird, Keisha, Englert, Kimberly, Permuy, Joe, Cossen, Kristina, Felner, Eric, Salam, Maamoun, Silverstein, Julie, Adamson, Samantha, Cedeno, Andrea, Meighan, Seema, Dauber, Andrew, Boeder, Schafer

المصدر: The New England Journal of Medicine. 387(13)

مصطلحات موضوعية: Adolescent, Adult, Aged, Bionics, Blood Glucose, Blood Glucose Self-Monitoring, Child, Diabetes Mellitus, Type 1, Glycated Hemoglobin, Humans, Hypoglycemic Agents, Insulin, Insulin Aspart, Insulin Infusion Systems, Insulin Lispro, Middle Aged, Young Adult

الوصف: BACKGROUND: Currently available semiautomated insulin-delivery systems require individualized insulin regimens for the initialization of therapy and meal doses based on carbohydrate counting for routine operation. In contrast, the bionic pancreas is initialized only on the basis of body weight, makes all dose decisions and delivers insulin autonomously, and uses meal announcements without carbohydrate counting. METHODS: In this 13-week, multicenter, randomized trial, we randomly assigned in a 2:1 ratio persons at least 6 years of age with type 1 diabetes either to receive bionic pancreas treatment with insulin aspart or insulin lispro or to receive standard care (defined as any insulin-delivery method with unblinded, real-time continuous glucose monitoring). The primary outcome was the glycated hemoglobin level at 13 weeks. The key secondary outcome was the percentage of time that the glucose level as assessed by continuous glucose monitoring was below 54 mg per deciliter; the prespecified noninferiority limit for this outcome was 1 percentage point. Safety was also assessed. RESULTS: A total of 219 participants 6 to 79 years of age were assigned to the bionic-pancreas group, and 107 to the standard-care group. The glycated hemoglobin level decreased from 7.9% to 7.3% in the bionic-pancreas group and did not change (was at 7.7% at both time points) in the standard-care group (mean adjusted difference at 13 weeks, -0.5 percentage points; 95% confidence interval [CI], -0.6 to -0.3; P

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الوصول الحر: https://escholarship.org/uc/item/1m5021wbTest

المؤلفون: Marcovecchio, M Loredana, Hendriks, A Emile J, Delfin, Carl, Battelino, Tadej, Danne, Thomas, Evans, Mark L, Johannesen, Jesper, Kaur, Simranjeet, Knip, Mikael, Overbergh, Lut, Pociot, Flemming, Todd, John A, Van der Schueren, Bart, Wicker, Linda S, Peakman, Mark, Mathieu, Chantal, INNODIA consortium

مصطلحات موضوعية: Age, Beta cell function, C-peptide, Prevention, Subgroups, Treatment, Type 1 diabetes, Humans, Diabetes Mellitus, Type 1, Adolescent, Child, Male, Female, Adult, Young Adult, Preschool, Autoantibodies, Glycated Hemoglobin, Blood Glucose, Cohort Studies, Infant, Europe, Middle Aged, Insulin-Secreting Cells

الوصف: AIMS/HYPOTHESIS: Type 1 diabetes is an heterogenous condition. Characterising factors explaining differences in an individual's clinical course and treatment response will have important clinical and research implications. Our aim was to explore type 1 diabetes heterogeneity, as assessed by clinical characteristics, autoantibodies, beta cell function and glycaemic outcomes, during the first 12 months from diagnosis, and how it relates to age at diagnosis. METHODS: Data were collected from the large INNODIA cohort of individuals (aged 1.0-45.0 years) newly diagnosed with type 1 diabetes, followed 3 monthly, to assess clinical characteristics, C-peptide, HbA1c and diabetes-associated antibodies, and their changes, during the first 12 months from diagnosis, across three age groups: <10 years; 10-17 years; and ≥18 years. RESULTS: The study population included 649 individuals (57.3% male; age 12.1±8.3 years), 96.9% of whom were positive for one or more diabetes-related antibodies. Baseline (IQR) fasting C-peptide was 242.0 (139.0-382.0) pmol/l (AUC 749.3 [466.2-1106.1] pmol/l × min), with levels increasing with age (p<0.001). Over time, C-peptide remained lower in participants aged <10 years but it declined in all age groups. In parallel, glucose levels progressively increased. Lower baseline fasting C-peptide, BMI SD score and presence of diabetic ketoacidosis at diagnosis were associated with lower stimulated C-peptide over time. HbA1c decreased during the first 3 months (p<0.001), whereas insulin requirement increased from 3 months post diagnosis (p<0.001). CONCLUSIONS/INTERPRETATION: In this large cohort with newly diagnosed type 1 diabetes, we identified age-related differences in clinical and biochemical variables. Of note, C-peptide was lower in younger children but there were no main age differences in its rate of decline.

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العلاقة: https://www.repository.cam.ac.uk/handle/1810/367743Test

الإتاحة: https://www.repository.cam.ac.uk/handle/1810/367743Test

المؤلفون: Demeterco-Berggren, Carla, Ebekozien, Osagie, Rompicherla, Saketh, Jacobsen, Laura, Accacha, Siham, Gallagher, Mary, Todd Alonso, G, Seyoum, Berhane, Vendrame, Francesco, Haw, J, Basina, Marina, Levy, Carol, Maahs, David

المصدر: The Journal of Clinical Endocrinology and Metabolism. 107(2)

مصطلحات موضوعية: COVID-19, age, hospitalization, type 1 diabetes, Adolescent, Adult, Age Factors, Aged, Aged, 80 and over, COVID-19, Child, Child, Preschool, Cross-Sectional Studies, Diabetes Mellitus, Type 1, Female, Hospitalization, Humans, Infant, Male, Middle Aged, Population Surveillance, Prognosis, Risk, Treatment Outcome, United States, Young Adult

الوصف: CONTEXT: COVID-19 morbidity and mortality are increased in type 1 diabetes (T1D), but few data focus on age-based outcomes. OBJECTIVE: This work aimed to quantify the risk for COVID-19-related hospitalization and adverse outcomes by age in people with T1D. METHODS: For this observational, multisite, cross-sectional study of patients with T1D and laboratory-confirmed COVID-19 from 56 clinical sites in the United States, data were collected from April 2020 to March 2021. The distribution of patient factors and outcomes across age groups (0-18, 19-40, and > 40 years) was examined. Descriptive statistics were used to describe the study population, and multivariate logistic regression models were used to analyze the relationship between age, adverse outcomes, and hospitalization. The main outcome measure was hospitalization for COVID-19. RESULTS: A total of 767 patients were analyzed. Fifty-four percent (n = 415) were aged 0 to 18 years, 32% (n = 247) were aged 19 to 40 years, and 14% (n = 105) were older than 40 years. A total of 170 patients were hospitalized, and 5 patients died. Compared to the 0- to 18-years age group, those older than 40 years had an adjusted odds ratio of 4.2 (95% CI, 2.28-7.83) for hospitalization after adjustment for sex, glycated hemoglobin A1c, race, insurance type, and comorbidities. CONCLUSION: Age older than 40 years is a risk factor for patients with T1D and COVID-19, with children and younger adults experiencing milder disease and better prognosis. This indicates a need for age-tailored treatments, immunization, and clinical management of individuals affected by T1D.

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الوصول الحر: https://escholarship.org/uc/item/9s56g2btTest

المؤلفون: Wu, Chien-Ting, Lidsky, Peter V, Xiao, Yinghong, Lee, Ivan T, Cheng, Ran, Nakayama, Tsuguhisa, Jiang, Sizun, Demeter, Janos, Bevacqua, Romina J, Chang, Charles A, Whitener, Robert L, Stalder, Anna K, Zhu, Bokai, Chen, Han, Goltsev, Yury, Tzankov, Alexandar, Nayak, Jayakar V, Nolan, Garry P, Matter, Matthias S, Andino, Raul, Jackson, Peter K

المصدر: Cell Metabolism. 33(8)

مصطلحات موضوعية: Diabetes, Pneumonia & Influenza, Prevention, Lung, Autoimmune Disease, Pneumonia, Infectious Diseases, Emerging Infectious Diseases, Clinical Research, Aetiology, 2.1 Biological and endogenous factors, Metabolic and endocrine, Good Health and Well Being, A549 Cells, Adult, Aged, Aged, 80 and over, Angiotensin-Converting Enzyme 2, Antigens, CD, Apoptosis, Apoptosis Regulatory Proteins, COVID-19, Case-Control Studies, Diabetes Mellitus, Female, Host-Pathogen Interactions, Humans, Insulin, Insulin-Secreting Cells, Male, Middle Aged, Neuropilin-1, Receptors, Transferrin, Receptors, Virus, SARS-CoV-2, Serine Endopeptidases, Spike Glycoprotein, Coronavirus, Virus Internalization, ACE2, SARS-CoV-2 spike protein, apoptosis, insulin, neuropilin 1, pancreatic beta cell, phosphoproteomics, type 1 diabetes, Biochemistry and Cell Biology, Medical Biochemistry and Metabolomics, Endocrinology & Metabolism

الوصف: Emerging evidence points toward an intricate relationship between the pandemic of coronavirus disease 2019 (COVID-19) and diabetes. While preexisting diabetes is associated with severe COVID-19, it is unclear whether COVID-19 severity is a cause or consequence of diabetes. To mechanistically link COVID-19 to diabetes, we tested whether insulin-producing pancreatic β cells can be infected by SARS-CoV-2 and cause β cell depletion. We found that the SARS-CoV-2 receptor, ACE2, and related entry factors (TMPRSS2, NRP1, and TRFC) are expressed in β cells, with selectively high expression of NRP1. We discovered that SARS-CoV-2 infects human pancreatic β cells in patients who succumbed to COVID-19 and selectively infects human islet β cells in vitro. We demonstrated that SARS-CoV-2 infection attenuates pancreatic insulin levels and secretion and induces β cell apoptosis, each rescued by NRP1 inhibition. Phosphoproteomic pathway analysis of infected islets indicates apoptotic β cell signaling, similar to that observed in type 1 diabetes (T1D). In summary, our study shows SARS-CoV-2 can directly induce β cell killing.

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الوصول الحر: https://escholarship.org/uc/item/0jt3m3tqTest

المؤلفون: Boeder, Schafer C, Gregory, Justin M, Giovannetti, Erin R, Pettus, Jeremy H

المصدر: Diabetes. 71(3)

مصطلحات موضوعية: Diabetes, Clinical Trials and Supportive Activities, Clinical Research, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Metabolic and endocrine, Adult, Benzhydryl Compounds, Blood Glucose, Diabetes Mellitus, Type 1, Double-Blind Method, Fasting, Fatty Acids, Nonesterified, Female, Glucagon, Glucose Clamp Technique, Glucosides, Glycemic Control, Humans, Hypoglycemia, Insulin, Male, Middle Aged, Sodium-Glucose Transporter 2 Inhibitors, Medical and Health Sciences, Endocrinology & Metabolism

الوصف: Individuals with type 1 diabetes have an impaired glucagon counterregulatory response to hypoglycemia. Sodium-glucose cotransporter (SGLT) inhibitors increase glucagon concentrations. We evaluated whether SGLT inhibition restores the glucagon counterregulatory hormone response to hypoglycemia. Adults with type 1 diabetes (n = 22) were treated with the SGLT2 inhibitor dapagliflozin (5 mg daily) or placebo for 4 weeks in a randomized, double-blind, crossover study. After each treatment phase, participants underwent a hyperinsulinemic-hypoglycemic clamp. Basal glucagon concentrations were 32% higher following dapagliflozin versus placebo, with a median within-participant difference of 2.75 pg/mL (95% CI 1.38-12.6). However, increased basal glucagon levels did not correlate with decreased rates of hypoglycemia and thus do not appear to be protective in avoiding hypoglycemia. During hypoglycemic clamp, SGLT2 inhibition did not change counterregulatory hormone concentrations, time to recovery from hypoglycemia, hypoglycemia symptoms, or cognitive function. Thus, despite raising basal glucagon concentrations, SGLT inhibitor treatment did not restore the impaired glucagon response to hypoglycemia. We propose that clinical reduction in hypoglycemia associated with these agents is a result of changes in diabetes care (e.g., lower insulin doses or improved glycemic variability) as opposed to a direct, physiologic effect of these medications on α-cell function.

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الوصول الحر: https://escholarship.org/uc/item/9cg0m1vxTest