المؤلفون: Kim M. Knudsen, Thomas R. Pieber, Julie Willard, Benedikte Bandak, Ulrike Hövelmann, Ramin Tehranchi, Leona Plum-Mörschel, Ronnie Aronson

المصدر: Diabetes Care

مصطلحات موضوعية: Adult, Blood Glucose, Randomization, Endocrinology, Diabetes and Metabolism, 030209 endocrinology & metabolism, Hypoglycemia, Placebo, Glucagon, 03 medical and health sciences, 0302 clinical medicine, Double-Blind Method, Diabetes mellitus, Internal Medicine, Clinical endpoint, Humans, Hypoglycemic Agents, Insulin, Medicine, 030212 general & internal medicine, Advanced and Specialized Nursing, Type 1 diabetes, Emerging Therapies: Drugs and Regimens, business.industry, medicine.disease, Diabetes Mellitus, Type 2, Tolerability, Anesthesia, business

الوصف: OBJECTIVE To evaluate the efficacy and safety of dasiglucagon, a ready-to-use, next-generation glucagon analog in aqueous formulation for subcutaneous dosing, for treatment of severe hypoglycemia in adults with type 1 diabetes. RESEARCH DESIGN AND METHODS This randomized, double-blind trial included 170 adult participants with type 1 diabetes, each randomly assigned to receive a single subcutaneous dose of 0.6 mg dasiglucagon, placebo, or 1 mg reconstituted glucagon (2:1:1 randomization) during controlled insulin-induced hypoglycemia. The primary end point was time to plasma glucose recovery, defined as an increase of ≥20 mg/dL from baseline without rescue intravenous glucose. The primary comparison was dasiglucagon versus placebo; reconstituted lyophilized glucagon was included as reference. RESULTS Median (95% CI) time to recovery was 10 (10, 10) minutes for dasiglucagon compared with 40 (30, 40) minutes for placebo (P < 0.001); the corresponding result for reconstituted glucagon was 12 (10, 12) minutes. In the dasiglucagon group, plasma glucose recovery was achieved within 15 min in all but one participant (99%), superior to placebo (2%; P < 0.001) and similar to glucagon (95%). Similar outcomes were observed for the other investigated time points at 10, 20, and 30 min after dosing. The most frequent adverse effects were nausea and vomiting, as expected with glucagon treatment. CONCLUSIONS Dasiglucagon provided rapid and effective reversal of hypoglycemia in adults with type 1 diabetes, with safety and tolerability similar to those reported for reconstituted glucagon injection. The ready-to-use, aqueous formulation of dasiglucagon offers the potential to provide rapid and reliable treatment of severe hypoglycemia.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f3218a52a5a65444c39c3f05875a3c86Test
http://europepmc.org/articles/PMC8247529Test

المؤلفون: Anne Kilvert, Jane Patmore, C.D. Walton, Rumaisa Banatwalla, Robert Gregory, Shafie Kamaruddin, Dennis Barnes, Harshal Deshmukh, Thozhukat Sathyapalan, Emma G. Wilmot, Niall Furlong, Roselle Herring, Robert E.J. Ryder, Simon Saunders, Parth Narendran

المصدر: Diabetes Care

مصطلحات موضوعية: Research design, Clinical audit, Adult, Blood Glucose, Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, 030209 endocrinology & metabolism, Glycemic Control, Hypoglycemia, Psychological Distress, State Medicine, Diabetic Ketoacidosis, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Interquartile range, Diabetes mellitus, Emerging Technologies: Data Systems and Devices, Internal Medicine, medicine, Diabetes Mellitus, Humans, Hypoglycemic Agents, 030212 general & internal medicine, Glycemic, Advanced and Specialized Nursing, Glycated Hemoglobin, Type 1 diabetes, Clinical Audit, business.industry, Blood Glucose Self-Monitoring, Middle Aged, Patient Acceptance of Health Care, medicine.disease, United Kingdom, Hospitalization, Distress, Hyperglycemia, Emergency medicine, Health Resources, Female, business, Stress, Psychological

الوصف: OBJECTIVE The FreeStyle Libre (FSL) flash glucose-monitoring device was made available on the U.K. National Health Service (NHS) drug tariff in 2017. This study aims to explore the U.K. real-world experience of FSL and the impact on glycemic control, hypoglycemia, diabetes-related distress, and hospital admissions. RESEARCH DESIGN AND METHODS Clinicians from 102 NHS hospitals in the U.K. submitted FSL user data, collected during routine clinical care, to a secure web-based tool held within the NHS N3 network. The t and Mann-Whitney U tests were used to compare the baseline and follow-up HbA1c and other baseline demographic characteristics. Linear regression analysis was used to identify predictors of change in HbA1c following the use of FSL. Within-person variations of HbA1c were calculated using . RESULTS Data were available for 10,370 FSL users (97% with type 1 diabetes), age 38.0 (±18.8) years, 51% female, diabetes duration 16.0 (±49.9) years, and BMI of 25.2 (±16.5) kg/m2 (mean [±SD]). FSL users demonstrated a −5.2 mmol/mol change in HbA1c, reducing from 67.5 (±20.9) mmol/mol (8.3%) at baseline to 62.3 (±18.5) mmol/mol (7.8%) after 7.5 (interquartile range 3.4–7.8) months of follow-up (n = 3,182) (P < 0.0001). HbA1c reduction was greater in those with initial HbA1c ≥69.5 mmol/mol (>8.5%), reducing from 85.5 (±16.1) mmol/mol (10%) to 73.1 (±15.8) mmol/mol (8.8%) (P < 0.0001). The baseline Gold score (score for hypoglycemic unawareness) was 2.7 (±1.8) and reduced to 2.4 (±1.7) (P < 0.0001) at follow-up. A total of 53% of those with a Gold score of ≥4 at baseline had a score CONCLUSIONS We show that the use of FSL was associated with significantly improved glycemic control and hypoglycemia awareness and a reduction in hospital admissions.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::54b95951e49c2544423cf31781b2f3efTest
http://europepmc.org/articles/PMC7440900Test

المؤلفون: Linda Gonder-Frederick, Harsimran Singh, Karen M. Schmidt, Daniel J. Cox, William L. Clarke, Jesse H. Grabman, Tom Banton, Karen S. Ingersoll

المصدر: Diabetes Care

مصطلحات موضوعية: Research design, Adult, Male, medicine.medical_specialty, Automobile Driving, Endocrinology, Diabetes and Metabolism, Minnesota, Motivational interviewing, 030209 endocrinology & metabolism, Motivational Interviewing, Risk Assessment, law.invention, 03 medical and health sciences, 0302 clinical medicine, Primary outcome, Randomized controlled trial, law, Risk Factors, Surveys and Questionnaires, Internal Medicine, medicine, Humans, 030212 general & internal medicine, Health Education, Advanced and Specialized Nursing, Glycated Hemoglobin, Type 1 diabetes, Internet, business.industry, Clinical Care/Education/Nutrition/Psychosocial Research, Accidents, Traffic, Virginia, Reproducibility of Results, Middle Aged, medicine.disease, Treatment period, Hypoglycemia, Diabetes Mellitus, Type 1, Logistic Models, Physical therapy, Health education, Female, Risk assessment, business, Boston

الوصف: OBJECTIVE Two aims of this study were to develop and validate A) a metric to identify drivers with type 1 diabetes at high risk of future driving mishaps and B) an online intervention to reduce mishaps among high-risk drivers. RESEARCH DESIGN AND METHODS To achieve aim A, in study 1, 371 drivers with type 1 diabetes from three U.S. regions completed a series of established questionnaires about diabetes and driving. They recorded their driving mishaps over the next 12 months. Questionnaire items that uniquely discriminated drivers who did and did not have subsequent driving mishaps were assembled into the Risk Assessment of Diabetic Drivers (RADD) scale. In study 2, 1,737 drivers with type 1 diabetes from all 50 states completed the RADD online. Among these, 118 low-risk (LR) and 372 high-risk (HR) drivers qualified for and consented to participate in a 2-month treatment period followed by 12 monthly recordings of driving mishaps. To address aim B, HR participants were randomized to receive either routine care (RC) or the online intervention “DiabetesDriving.com” (DD.com). Half of the DD.com participants received a motivational interview (MI) at the beginning and end of the treatment period to boost participation and efficacy. All of the LR participants were assigned to RC. In both studies, the primary outcome variable was driving mishaps. RESULTS Related to aim A, in study 1, the RADD demonstrated 61% sensitivity and 75% specificity. Participants in the upper third of the RADD distribution (HR), compared with those in the lower third (LR), reported 3.03 vs. 0.87 mishaps/driver/year, respectively (P < 0.001). In study 2, HR and LR participants receiving RC reported 4.3 and 1.6 mishaps/driver/year, respectively (P < 0.001). Related to aim B, in study 2, MIs did not enhance participation or efficacy, so the DD.com and DD.com + MI groups were combined. DD.com participants reported fewer hypoglycemia-related driving mishaps than HR participants receiving RC (P = 0.01), but more than LR participants receiving RC, reducing the difference between the HR and LR participants receiving RC by 63%. HR drivers differed from LR drivers at baseline across a variety of hypoglycemia and driving parameters. CONCLUSIONS The RADD identified higher-risk drivers, and identification seemed relatively stable across time, samples, and procedures. This 11-item questionnaire could inform patients at higher risk, and their clinicians, that they should take preventive steps to reduce driving mishaps, which was accomplished in aim B using DD.com.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::313f8f9867d8323df0c0d09bfe63650eTest
http://europepmc.org/articles/PMC5439415Test

المؤلفون: Flatt, Anneliese JS, Little, Stuart A, Speight, Jane, Leelarathna, Lalantha, Walkinshaw, Emma, Tan, Horng Kai, Bowes, Anita, Lubina-Solomon, Alexandra, Holmes-Truscott, Elizabeth, Chadwick, Thomas J, Wood, Ruth, McDonald, Timothy J, Kerr, David, Flanagan, Daniel, Brooks, Augustin, Heller, Simon R, Evans, Mark L, Shaw, James AM

مصطلحات موضوعية: Adolescent, Adult, Aged, Awareness, Blood Glucose, Blood Glucose Self-Monitoring, Cognition Disorders, Diabetes Mellitus, Type 1, Female, Humans, Hypoglycemia, Insulin, Insulin Infusion Systems, Male, Middle Aged, Prognosis, Recurrence, Risk Factors, Severity of Illness Index, Treatment Outcome, Young Adult

الوصف: OBJECTIVE: The HypoCOMPaSS study was designed to test the hypothesis that successful avoidance of biochemical hypoglycemia without compromising overall glycemic control would restore sufficient hypoglycemia awareness to prevent recurrent severe hypoglycemia in the majority of participants with established type 1 diabetes. Before starting the study, we planned to investigate associations between baseline characteristics and recurrent severe hypoglycemia over 2 years' follow-up. RESEARCH DESIGN AND METHODS: A total of 96 adults with type 1 diabetes and impaired awareness of hypoglycemia participated in a 24-week 2 × 2 factorial randomized controlled trial comparing insulin delivery and glucose monitoring modalities, with the goal of rigorous biochemical hypoglycemia avoidance. The analysis included 71 participants who had experienced severe hypoglycemia in the 12-month prestudy with confirmed absence (complete responder) or presence (incomplete responder) of severe hypoglycemia over 24 months' follow-up. RESULTS: There were 43 (61%) complete responders and 28 (39%) incomplete responders experiencing mean ± SD 1.5 ± 1.0 severe hypoglycemia events/person-year. At 24 months, incomplete responders spent no more time with glucose ≤3 mmol/L (1.4 ± 2.1% vs. 3.0 ± 4.8% for complete responders; P = 0.26), with lower total daily insulin dose (0.45 vs. 0.58 units/24 h; P = 0.01) and greater impairment of hypoglycemia awareness (Clarke score: 3.8 ± 2.2 vs. 2.0 ± 1.9; P = 0.01). Baseline severe hypoglycemia rate (16.9 ± 16.3 vs. 6.4 ± 10.8 events/person-year; P = 0.002) and fear of hypoglycemia were higher in incomplete responders. Peripheral neuropathy was more prevalent in incomplete responders (11 [39%] vs. 2 [4.7%]; P < 0.001) with a trend toward increased autonomic neuropathy. CONCLUSIONS: Recurrent severe hypoglycemia was associated with higher preintervention severe hypoglycemia rate, fear of hypoglycemia, and concomitant neuropathy.

وصف الملف: Print-Electronic; application/vnd.openxmlformats-officedocument.wordprocessingml.document

العلاقة: https://www.repository.cam.ac.uk/handle/1810/299534Test

الإتاحة: https://doi.org/10.17863/CAM.46608Test
https://www.repository.cam.ac.uk/handle/1810/299534Test

المؤلفون: Leelarathna, Lalantha, Little, Stuart A, Walkinshaw, Emma, Tan, Horng Kai, Lubina-Solomon, Alexandra, Kumareswaran, Kavita, Lane, Annette P, Chadwick, Thomas, Marshall, Sally M, Speight, Jane, Flanagan, Daniel, Heller, Simon R, Shaw, James AM, Evans, Mark L

مصطلحات موضوعية: Adult, Awareness, Blood Glucose, Diabetes Mellitus, Type 1, Dose-Response Relationship, Drug, Female, Glucose Clamp Technique, Glycated Hemoglobin, Humans, Hypoglycemia, Hypoglycemic Agents, Insulin, Insulin Infusion Systems, Male, Middle Aged, Treatment Outcome

الوصف: OBJECTIVE: Impaired awareness of hypoglycemia (IAH) and defective counterregulation significantly increase severe hypoglycemia risk in type 1 diabetes (T1D). We evaluated restoration of IAH/defective counterregulation by a treatment strategy targeted at hypoglycemia avoidance in adults with T1D with IAH (Gold score ≥4) participating in the U.K.-based multicenter HypoCOMPaSS randomized controlled trial. RESEARCH DESIGN AND METHODS: Eighteen subjects with T1D and IAH (mean ± SD age 50 ± 9 years, T1D duration 35 ± 10 years, HbA1c 8.1 ± 1.0% [65 ± 10.9 mmol/mol]) underwent stepped hyperinsulinemic-hypoglycemic clamp studies before and after a 6-month intervention. The intervention comprised the HypoCOMPaSS education tool in all and randomized allocation, in a 2 × 2 factorial study design, to multiple daily insulin analog injections or continuous subcutaneous insulin infusion therapy and conventional glucose monitoring or real-time continuous glucose monitoring. Symptoms, cognitive function, and counterregulatory hormones were measured at each glucose plateau (5.0, 3.8, 3.4, 2.8, and 2.4 mmol/L), with each step lasting 40 min with subjects kept blinded to their actual glucose value throughout clamp studies. RESULTS: After intervention, glucose concentrations at which subjects first felt hypoglycemic increased (mean ± SE from 2.6 ± 0.1 to 3.1 ± 0.2 mmol/L, P = 0.02), and symptom and plasma metanephrine responses to hypoglycemia were higher (median area under curve for symptoms, 580 [interquartile range {IQR} 420-780] vs. 710 [460-1,260], P = 0.02; metanephrine, 2,412 [-3,026 to 7,279] vs. 5,180 [-771 to 11,513], P = 0.01). Glycemic threshold for deterioration of cognitive function measured by four-choice reaction time was unchanged, while the color-word Stroop test showed a degree of adaptation. CONCLUSIONS: Even in long-standing T1D, IAH and defective counterregulation may be improved by a clinical strategy aimed at hypoglycemia avoidance.

وصف الملف: Print-Electronic; application/pdf

العلاقة: https://www.repository.cam.ac.uk/handle/1810/302227Test

الإتاحة: https://doi.org/10.17863/CAM.49301Test
https://www.repository.cam.ac.uk/handle/1810/302227Test

المؤلفون: Robert S. Sherwin, Douglas L. Rothman, Yuyan Ding, Lihong Jiang, Wai Lam, Jessica Leventhal, Graeme F. Mason, Janice J. Hwang, Elizabeth Sanchez Rangel, Feng Dai, Xiaoning Fan

مصطلحات موضوعية: 0301 basic medicine, Adult, Blood Glucose, Male, medicine.medical_specialty, Complications, endocrine system diseases, Endocrinology, Diabetes and Metabolism, Hippocampus, 030209 endocrinology & metabolism, Carbohydrate metabolism, Hypoglycemia, Rats, Sprague-Dawley, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Diabetes mellitus, Internal Medicine, medicine, Animals, Humans, Hypoglycemic Agents, Glycemic, Glycated Hemoglobin, Type 1 diabetes, business.industry, Glucose transporter, nutritional and metabolic diseases, Brain, Metabolism, Models, Theoretical, medicine.disease, Rats, 030104 developmental biology, Endocrinology, Diabetes Mellitus, Type 1, Glucose, Hyperglycemia, Female, business

الوصف: The impact of glycemic variability on brain glucose transport kinetics among individuals with type 1 diabetes mellitus (T1DM) remains unclear. Fourteen individuals with T1DM (age 35 ± 4 years; BMI 26.0 ± 1.4 kg/m2; HbA1c 7.6 ± 0.3) and nine healthy control participants (age 32 ± 4; BMI 23.1 ± 0.8; HbA1c 5.0 ± 0.1) wore a continuous glucose monitor (Dexcom) to measure hypoglycemia, hyperglycemia, and glycemic variability for 5 days followed by 1H MRS scanning in the occipital lobe to measure the change in intracerebral glucose levels during a 2-h glucose clamp (target glucose concentration 220 mg/dL). Hyperglycemic clamps were also performed in a rat model of T1DM to assess regional differences in brain glucose transport and metabolism. Despite a similar change in plasma glucose levels during the hyperglycemic clamp, individuals with T1DM had significantly smaller increments in intracerebral glucose levels (P = 0.0002). Moreover, among individuals with T1DM, the change in brain glucose correlated positively with the lability index (r = 0.67, P = 0.006). Consistent with findings in humans, streptozotocin-treated rats had lower brain glucose levels in the cortex, hippocampus, and striatum compared with control rats. These findings that glycemic variability is associated with brain glucose levels highlight the need for future studies to investigate the impact of glycemic variability on brain glucose kinetics.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::361c46a1688dd976f50b0ff6c1c68c18Test
https://europepmc.org/articles/PMC6302539Test/

المؤلفون: Armand Mbanya, Ilan Gabriely, Meredith Hawkins, Nora Tomuta, Akankasha Goyal, Eric Lontchi-Yimagou, Harry Shamoon, Michelle Carey, Oana A. Sandu, Rebekah Gospin, Raphael Hulkower

المصدر: Diabetes

مصطلحات موضوعية: 0301 basic medicine, Adult, Blood Glucose, Male, medicine.medical_specialty, Epinephrine, Hydrocortisone, medicine.drug_class, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, 030209 endocrinology & metabolism, Hypoglycemia, 03 medical and health sciences, Norepinephrine, 0302 clinical medicine, Opioid receptor, Internal medicine, Diabetes mellitus, Internal Medicine, Medicine, Humans, Insulin, Glycemic, Type 1 diabetes, Cross-Over Studies, C-Peptide, Morphine, business.industry, Glucose clamp technique, medicine.disease, 3. Good health, 030104 developmental biology, Endocrinology, Metabolism, Glucose, Receptors, Opioid, Glucose Clamp Technique, Female, business, medicine.drug

الوصف: Although intensive glycemic control improves outcomes in type 1 diabetes mellitus (T1DM), iatrogenic hypoglycemia limits its attainment. Recurrent and/or antecedent hypoglycemia causes blunting of protective counterregulatory responses, known as hypoglycemia-associated autonomic failure (HAAF). To determine whether and how opioid receptor activation induces HAAF in humans, 12 healthy subjects without diabetes (7 men, age 32.3 ± 2.2 years, BMI 25.1 ± 1.0 kg/m2) participated in two study protocols in random order over two consecutive days. On day 1, subjects received two 120-min infusions of either saline or morphine (0.1 μg/kg/min), separated by a 120-min break (all euglycemic). On day 2, subjects underwent stepped hypoglycemic clamps (nadir 60 mg/dL) with evaluation of counterregulatory hormonal responses, endogenous glucose production (EGP, using 6,6-D2-glucose), and hypoglycemic symptoms. Morphine induced an ∼30% reduction in plasma epinephrine response together with reduced EGP and hypoglycemia-associated symptoms on day 2. Therefore, we report the first studies in humans demonstrating that pharmacologic opioid receptor activation induces some of the clinical and biochemical features of HAAF, thus elucidating the individual roles of various receptors involved in HAAF’s development and suggesting novel pharmacologic approaches for safer intensive glycemic control in T1DM.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::62135a77dc893f6ae0a20523ecbaa516Test
http://europepmc.org/articles/PMC5652610Test

المؤلفون: Michael R, Rickels, Stephanie N, DuBose, Elena, Toschi, Roy W, Beck, Alandra S, Verdejo, Howard, Wolpert, Martin J, Cummins, Brett, Newswanger, Michael C, Riddell, Steve, Prestrelski

مصطلحات موضوعية: Adult, Male, Blood Glucose, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, 030209 endocrinology & metabolism, 030204 cardiovascular system & hematology, Hypoglycemia, Glucagon, 03 medical and health sciences, 0302 clinical medicine, Insulin Infusion Systems, Internal medicine, Diabetes mellitus, Internal Medicine, medicine, Aerobic exercise, Insulin, Humans, Exercise physiology, Exercise, Glycemic, Advanced and Specialized Nursing, Type 1 diabetes, Cross-Over Studies, Dose-Response Relationship, Drug, Emerging Therapies: Drugs and Regimens, business.industry, Fasting, medicine.disease, Endocrinology, Diabetes Mellitus, Type 1, Glucose, Female, business

الوصف: OBJECTIVE Patients with type 1 diabetes who do aerobic exercise often experience a drop in blood glucose concentration that can result in hypoglycemia. Current approaches to prevent exercise-induced hypoglycemia include reduction in insulin dose or ingestion of carbohydrates, but these strategies may still result in hypoglycemia or hyperglycemia. We sought to determine whether mini-dose glucagon (MDG) given subcutaneously before exercise could prevent subsequent glucose lowering and to compare the glycemic response to current approaches for mitigating exercise-associated hypoglycemia. RESEARCH DESIGN AND METHODS We conducted a four-session, randomized crossover trial involving 15 adults with type 1 diabetes treated with continuous subcutaneous insulin infusion who exercised fasting in the morning at ∼55% VO2max for 45 min under conditions of no intervention (control), 50% basal insulin reduction, 40-g oral glucose tablets, or 150-μg subcutaneous glucagon (MDG). RESULTS During exercise and early recovery from exercise, plasma glucose increased slightly with MDG compared with a decrease with control and insulin reduction and a greater increase with glucose tablets (P < 0.001). Insulin levels were not different among sessions, whereas glucagon increased with MDG administration (P < 0.001). Hypoglycemia (plasma glucose CONCLUSIONS MDG may be more effective than insulin reduction for preventing exercise-induced hypoglycemia and may result in less postintervention hyperglycemia than ingestion of carbohydrate.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::da4f05614dfdc7d82e56048e813d1b91Test
https://europepmc.org/articles/PMC6463733Test/

المؤلفون: Oliver, N, Gimenez, M, Calhoun, P, Cohen, N, Moscardo, V, Hermanns, N, Freckmann, G, Reddy, M, Heinemann, L

المساهمون: National Institute for Health Research, Imperial College Healthcare NHS Trust- BRC Funding

المصدر: 58 ; 53

مصطلحات موضوعية: Science & Technology, Life Sciences & Biomedicine, Endocrinology & Metabolism, DAILY INSULIN INJECTIONS, INTENSIVE TREATMENT, ADULTS, MULTICENTER, DIAMOND, Adult, Blood Glucose, Blood Glucose Self-Monitoring, Diabetes Mellitus, Type 1, Dose-Response Relationship, Drug, Female, Glycated Hemoglobin A, Humans, Hypoglycemia, Hypoglycemic Agents, Injections, Subcutaneous, Insulin, Male, Middle Aged, 11 Medical and Health Sciences

جغرافية الموضوع: United States

الوصف: OBJECTIVE: The inverse relationship between overall glucose control and hypoglycemia risk is weakened by the use of real-time continuous glucose monitoring (rtCGM). We assess the relationship between glucose control and hypoglycemia in people with type 1 diabetes using multiple-dose injection (MDI) regimens, including those at highest risk of hypoglycemia. RESEARCH DESIGN AND METHODS: CGM data from the intervention (rtCGM) and control (self-monitored blood glucose [SMBG]) phases of the Multiple Daily Injections and Continuous Glucose Monitoring in Diabetes (DIAMOND) and HypoDE studies were analyzed. The relationship between glucose control (HbA1c and mean rtCGM glucose levels) and percentage time spent in hypoglycemia was explored for thresholds of 3.9 mmol/L (70 mg/dL) and 3.0 mmol/L (54 mg/dL), and ANOVA across the range of HbA1c and mean glucose was performed. RESULTS: A nonlinear relationship between mean glucose and hypoglycemia was identified at baseline, with the steepest relationship seen at lower values of mean glucose. The use of rtCGM reduces the exposure to hypoglycemia at all thresholds and flattens the relationship between overall glucose and hypoglycemia, with the most marked impact at lower values of mean glucose and HbA1c. Exposure to hypoglycemia varied at all thresholds across the range of overall glucose at baseline, in the SMBG group, and with rtCGM, but the relationships were weaker in the rtCGM group. CONCLUSIONS: Usage of rtCGM can flatten and attenuate the relationship between overall glucose control and hypoglycemia, exerting its greatest impact at lower values of HbA1c and mean glucose in people with type 1 diabetes using MDI regimens and at highest risk of hypoglycemia.

العلاقة: Diabetes Care; http://hdl.handle.net/10044Test/1/73596; RDA11 79560; RDA29

الإتاحة: https://doi.org/10.2337/dc19-0977Test
http://hdl.handle.net/10044Test/1/73596

المؤلفون: Behary, P, Tharakan, G, Alexiadou, K, Johnson, N, Wewer Albrechtsen, NJ, Kenkre, J, Cuenco, J, Hope, D, Anyiam, O, Choudhury, S, Alessimii, H, Poddar, A, Minnion, J, Doyle, C, Frost, G, Le Roux, C, Purkayastha, S, Moorthy, K, Dhillo, W, Holst, JJ, Ahmed, AR, Prevost, AT, Bloom, SR, Tan, TM

المساهمون: National Institute for Health Research, The Jon Moulton Charity Trust, Medical Research Council (MRC)

المصدر: 1453 ; 1446

مصطلحات موضوعية: Science & Technology, Life Sciences & Biomedicine, Endocrinology & Metabolism, DUTCH EATING BEHAVIOR, FOOD-INTAKE, INSULIN SENSITIVITY, ENERGY-EXPENDITURE, BARIATRIC SURGERY, GLUCAGON, QUESTIONNAIRE, OVERWEIGHT, APPETITE, PYY3-36, Adult, Blood Glucose, Blood Glucose Self-Monitoring, Body Weight, Diabetes Mellitus, Type 2, Drug Therapy, Combination, Female, Glucagon-Like Peptide 1, Humans, Hypoglycemia, Infusions, Subcutaneous, Insulin, Male, Meals

جغرافية الموضوع: United States

الوصف: OBJECTIVE: Roux-en-Y gastric bypass (RYGB) augments postprandial secretion of glucagon-like peptide 1 (GLP-1), oxyntomodulin (OXM), and peptide YY (PYY). Subcutaneous infusion of these hormones ("GOP"), mimicking postprandial levels, reduces energy intake. Our objective was to study the effects of GOP on glycemia and body weight when given for 4 weeks to patients with diabetes and obesity. RESEARCH DESIGN AND METHODS: In this single-blinded mechanistic study, obese patients with prediabetes/diabetes were randomized to GOP (n = 15) or saline (n = 11) infusion for 4 weeks. We also studied 21 patients who had undergone RYGB and 22 patients who followed a very low-calorie diet (VLCD) as unblinded comparators. Outcomes measured were 1) body weight, 2) fructosamine levels, 3) glucose and insulin during a mixed meal test (MMT), 4) energy expenditure (EE), 5) energy intake (EI), and 6) mean glucose and measures of glucose variability during continuous glucose monitoring. RESULTS: GOP infusion was well tolerated over the 4-week period. There was a greater weight loss (P = 0.025) with GOP (mean change -4.4 [95% CI -5.3, -3.5] kg) versus saline (-2.5 [-4.1, -0.9] kg). GOP led to a greater improvement (P = 0.0026) in fructosamine (-44.1 [-62.7, -25.5] µmol/L) versus saline (-11.7 [-18.9, -4.5] µmol/L). Despite a smaller weight loss compared with RYGB and VLCD, GOP led to superior glucose tolerance after a mixed-meal stimulus and reduced glycemic variability compared with RYGB and VLCD. CONCLUSIONS: GOP infusion improves glycemia and reduces body weight. It achieves superior glucose tolerance and reduced glucose variability compared with RYGB and VLCD. GOP is a viable alternative for the treatment of diabetes with favorable effects on body weight.

العلاقة: Diabetes Care; http://hdl.handle.net/10044Test/1/71396; EME/13/121/07; Prof Alex Miras; MR/K02115X/1

الإتاحة: https://doi.org/10.2337/dc19-0449Test
http://hdl.handle.net/10044Test/1/71396