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2.
Diabetes Care ; 43(3): 607-615, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31937608

RESUMO

OBJECTIVE: Assess the efficacy of inControl AP, a mobile closed-loop control (CLC) system. RESEARCH DESIGN AND METHODS: This protocol, NCT02985866, is a 3-month parallel-group, multicenter, randomized unblinded trial designed to compare mobile CLC with sensor-augmented pump (SAP) therapy. Eligibility criteria were type 1 diabetes for at least 1 year, use of insulin pumps for at least 6 months, age ≥14 years, and baseline HbA1c <10.5% (91 mmol/mol). The study was designed to assess two coprimary outcomes: superiority of CLC over SAP in continuous glucose monitor (CGM)-measured time below 3.9 mmol/L and noninferiority in CGM-measured time above 10 mmol/L. RESULTS: Between November 2017 and May 2018, 127 participants were randomly assigned 1:1 to CLC (n = 65) versus SAP (n = 62); 125 participants completed the study. CGM time below 3.9 mmol/L was 5.0% at baseline and 2.4% during follow-up in the CLC group vs. 4.7% and 4.0%, respectively, in the SAP group (mean difference -1.7% [95% CI -2.4, -1.0]; P < 0.0001 for superiority). CGM time above 10 mmol/L was 40% at baseline and 34% during follow-up in the CLC group vs. 43% and 39%, respectively, in the SAP group (mean difference -3.0% [95% CI -6.1, 0.1]; P < 0.0001 for noninferiority). One severe hypoglycemic event occurred in the CLC group, which was unrelated to the study device. CONCLUSIONS: In meeting its coprimary end points, superiority of CLC over SAP in CGM-measured time below 3.9 mmol/L and noninferiority in CGM-measured time above 10 mmol/L, the study has demonstrated that mobile CLC is feasible and could offer certain usability advantages over embedded systems, provided the connectivity between system components is stable.

4.
J Diabetes Sci Technol ; : 1932296819894974, 2019 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-31867988

RESUMO

BACKGROUND: Knowledge regarding the burden and predictors of hypoglycemia among older adults with type 1 diabetes (T1D) is limited. METHODS: We analyzed baseline data from the Wireless Innovations for Seniors with Diabetes Mellitus (WISDM) study, which enrolled participants at 22 sites in the United States. Eligibility included clinical diagnosis of T1D, age ≥60 years, no real-time continuous glucose monitoring (CGM) use in prior three months, and HbA1c <10.0%. Blinded CGM data from 203 participants with at least 240 hours were included in the analyses. RESULTS: Median age of the cohort was 68 years (52% female, 93% non-Hispanic white, and 53% used insulin pumps). Mean HbA1c was 7.5%. Median time spent in the glucose range <70 mg/dL was 5.0% (72 min/day) and <54 mg/dL was 1.6% (24 min/day). Among all factors analyzed, only reduced hypoglycemia awareness was associated with greater time spent <54 mg/dL (median time of 2.7% vs 1.3% [39 vs 19 minutes per day] for reduced awareness vs aware/uncertain, respectively, P = .03). Participants spent a mean 56% of total time in target glucose range of 70-180 mg/dL and 37% of time above 180 mg/dL. CONCLUSIONS: Over half of older T1D participants spent at least an hour a day with glucose levels <70 mg/dL. Those with reduced hypoglycemia awareness spent over twice as much time than those without in a serious hypoglycemia range (glucose levels <54 mg/dL). Interventions to reduce exposure to clinically significant hypoglycemia and increase time in range are urgently needed in this age group.

5.
N Engl J Med ; 381(18): 1707-1717, 2019 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-31618560

RESUMO

BACKGROUND: Closed-loop systems that automate insulin delivery may improve glycemic outcomes in patients with type 1 diabetes. METHODS: In this 6-month randomized, multicenter trial, patients with type 1 diabetes were assigned in a 2:1 ratio to receive treatment with a closed-loop system (closed-loop group) or a sensor-augmented pump (control group). The primary outcome was the percentage of time that the blood glucose level was within the target range of 70 to 180 mg per deciliter (3.9 to 10.0 mmol per liter), as measured by continuous glucose monitoring. RESULTS: A total of 168 patients underwent randomization; 112 were assigned to the closed-loop group, and 56 were assigned to the control group. The age range of the patients was 14 to 71 years, and the glycated hemoglobin level ranged from 5.4 to 10.6%. All 168 patients completed the trial. The mean (±SD) percentage of time that the glucose level was within the target range increased in the closed-loop group from 61±17% at baseline to 71±12% during the 6 months and remained unchanged at 59±14% in the control group (mean adjusted difference, 11 percentage points; 95% confidence interval [CI], 9 to 14; P<0.001). The results with regard to the main secondary outcomes (percentage of time that the glucose level was >180 mg per deciliter, mean glucose level, glycated hemoglobin level, and percentage of time that the glucose level was <70 mg per deciliter or <54 mg per deciliter [3.0 mmol per liter]) all met the prespecified hierarchical criterion for significance, favoring the closed-loop system. The mean difference (closed loop minus control) in the percentage of time that the blood glucose level was lower than 70 mg per deciliter was -0.88 percentage points (95% CI, -1.19 to -0.57; P<0.001). The mean adjusted difference in glycated hemoglobin level after 6 months was -0.33 percentage points (95% CI, -0.53 to -0.13; P = 0.001). In the closed-loop group, the median percentage of time that the system was in closed-loop mode was 90% over 6 months. No serious hypoglycemic events occurred in either group; one episode of diabetic ketoacidosis occurred in the closed-loop group. CONCLUSIONS: In this 6-month trial involving patients with type 1 diabetes, the use of a closed-loop system was associated with a greater percentage of time spent in a target glycemic range than the use of a sensor-augmented insulin pump. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases; iDCL ClinicalTrials.gov number, NCT03563313.).


Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Sistemas de Infusão de Insulina , Insulina/administração & dosagem , Pâncreas Artificial , Adolescente , Adulto , Idoso , Glicemia/análise , Diabetes Mellitus Tipo 1/sangue , Desenho de Equipamento , Feminino , Hemoglobina A Glicada/análise , Humanos , Hipoglicemiantes/efeitos adversos , Insulina/efeitos adversos , Sistemas de Infusão de Insulina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Pâncreas Artificial/efeitos adversos , Adulto Jovem
6.
Clin Transplant ; 33(10): e13719, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31545535

RESUMO

BACKGROUND: Current therapy for Type 1 diabetes (T1D) is characterized by significant glucose variability (GV). Pancreas transplantation (PT) is performed in certain T1D patients with and without end-stage renal disease. To date, GV has been examined to a limited extent after PT. METHODS: We investigated GV using continuous glucose monitoring (CGM) 3-6 weeks after PT. RESULTS: Eleven patients had simultaneous kidney pancreas transplantation (SPK), nine pancreas after kidney (PAK), and six pancreas transplantation alone (PTA). Mean CGM showed no difference between SPK, 126.5 ± 13.9, PAK 119.9 ± 12.8, and PTA 131.1 ± 29 mg/dL (P value .6). Percentage of time in range (TIR, 70-180 mg/dL) was 92% for SPK, 93.4% in PAK, and 88.5% in PTA with only 0.3%, 1.5%, and 0.3% of time <70 mg/dL. Percentage >180 mg/dL was 7.9% for SPK, 4.9% PAK, and 11% in PTA. Other measures of GV were similar in the three cohorts. In six patients, CGM was performed before and after PT and improved significantly. GV was also better compared with a matched cohort of T1D patients. CONCLUSIONS: All 3 types of PT resulted in excellent glucose control 3-6 weeks post-procedure. CGM outcomes represent an important objective outcome after PT.

7.
Stem Cell Reports ; 13(2): 307-321, 2019 08 13.
Artigo em Inglês | MEDLINE | ID: mdl-31378674

RESUMO

Generation of functional ß cells from pluripotent sources would accelerate diagnostic and therapeutic applications for diabetes research and therapy. However, it has been challenging to generate competent ß cells with dynamic insulin-secretory capacity to glucose and incretin stimulations. We introduced transcription factors, critical for ß-cell development and function, in differentiating human induced pluripotent stem cells (PSCs) and assessed the impact on the functionality of derived ß-cell (psBC) progeny. A perifusion system revealed stepwise transduction of the PDX1, NEUROG3, and MAFA triad (PNM) enabled in vitro generation of psBCs with glucose and GLP-1 responsiveness within 3 weeks. PNM transduction upregulated genes associated with glucose sensing, insulin secretion, and ß-cell maturation. In recipient diabetic mice, PNM-transduced psBCs showed glucose-responsive insulin secretion as early as 1 week post transplantation. Thus, enhanced pre-emptive ß-cell specification of PSCs by PNM drives generation of glucose- and incretin-responsive psBCs in vitro, offering a competent tissue-primed biotherapy.

8.
Endocr Rev ; 40(5): 1318-1352, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31081877

RESUMO

This review covers the epidemiology, pathophysiology, clinical features, diagnosis, and management of diabetic gastroparesis, and more broadly diabetic gastroenteropathy, which encompasses all the gastrointestinal manifestations of diabetes mellitus. Up to 50% of patients with type 1 and type 2 DM and suboptimal glycemic control have delayed gastric emptying (GE), which can be documented with scintigraphy, 13C breath tests, or a wireless motility capsule; the remainder have normal or rapid GE. Many patients with delayed GE are asymptomatic; others have dyspepsia (i.e., mild to moderate indigestion, with or without a mild delay in GE) or gastroparesis, which is a syndrome characterized by moderate to severe upper gastrointestinal symptoms and delayed GE that suggest, but are not accompanied by, gastric outlet obstruction. Gastroparesis can markedly impair quality of life, and up to 50% of patients have significant anxiety and/or depression. Often the distinction between dyspepsia and gastroparesis is based on clinical judgement rather than established criteria. Hyperglycemia, autonomic neuropathy, and enteric neuromuscular inflammation and injury are implicated in the pathogenesis of delayed GE. Alternatively, there are limited data to suggest that delayed GE may affect glycemic control. The management of diabetic gastroparesis is guided by the severity of symptoms, the magnitude of delayed GE, and the nutritional status. Initial options include dietary modifications, supplemental oral nutrition, and antiemetic and prokinetic medications. Patients with more severe symptoms may require a venting gastrostomy or jejunostomy and/or gastric electrical stimulation. Promising newer therapeutic approaches include ghrelin receptor agonists and selective 5-hydroxytryptamine receptor agonists.

9.
BMJ Open Diabetes Res Care ; 7(1): e000591, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30899528

RESUMO

Objective: Insulin-dependent diabetes can occur with immune checkpoint inhibitor (ICI) therapy. We aimed to characterize the frequency, natural history and potential predictors of ICI-induced diabetes. Research design and methods: We reviewed 1444 patients treated with ICIs over 6 years at our cancer center, and from the 1163 patients who received programmed cell death protein 1 (PD-1) inhibitors, we identified 21 such cases, 12 of which developed new-onset insulin-dependent diabetes and 9 experienced worsening of pre-existing type 2 diabetes. Results: ICI-induced diabetes occurred most frequently with pembrolizumab (2.2%) compared with nivolumab (1%) and ipilimumab (0%). The median age was 61 years, and body mass index was 31 kg/m2, which are both higher than expected for spontaneous type 1 diabetes. Other immune-related adverse events occurred in 62%, the most common being immune mediated thyroid disease. New-onset insulin-dependent diabetes developed after a median of four cycles or 5 months; 67% presented with diabetic ketoacidosis and 83% with low or undetectable C-peptide. Autoantibodies were elevated in 5/7 (71%) at the time of new-onset diabetes. Diabetes did not resolve during a median follow-up of 1 year. Conclusions: PD-1 inhibitors can lead to insulin deficiency presenting as new-onset diabetes or worsening of pre-existing type 2 diabetes, with a frequency of 1.8 %. The underlying mechanism appears similar to spontaneous type 1 diabetes but there is a faster progression to severe insulin deficiency. Better characterization of ICI-induced diabetes will improve patient care and enhance our understanding of immune-mediated diabetes.

10.
Diabetes Technol Ther ; 21(2): 73-80, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30649925

RESUMO

BACKGROUND: Use of artificial pancreas (AP) requires seamless interaction of device components, such as continuous glucose monitor (CGM), insulin pump, and control algorithm. Mobile AP configurations also include a smartphone as computational hub and gateway to cloud applications (e.g., remote monitoring and data review and analysis). This International Diabetes Closed-Loop study was designed to demonstrate and evaluate the operation of the inControl AP using different CGMs and pump modalities without changes to the user interface, user experience, and underlying controller. METHODS: Forty-three patients with type 1 diabetes (T1D) were enrolled at 10 clinical centers (7 United States, 3 Europe) and 41 were included in the analyses (39% female, >95% non-Hispanic white, median T1D duration 16 years, median HbA1c 7.4%). Two CGMs and two insulin pumps were tested by different study participants/sites using the same system hub (a smartphone) during 2 weeks of in-home use. RESULTS: The major difference between the system components was the stability of their wireless connections with the smartphone. The two sensors achieved similar rates of connectivity as measured by percentage time in closed loop (75% and 75%); however, the two pumps had markedly different closed-loop adherence (66% vs. 87%). When connected, all system configurations achieved similar glycemic outcomes on AP control (73% [mean] time in range: 70-180 mg/dL, and 1.7% [median] time <70 mg/dL). CONCLUSIONS: CGMs and insulin pumps can be interchangeable in the same Mobile AP system, as long as these devices achieve certain levels of reliability and wireless connection stability.


Assuntos
Glicemia/análise , Diabetes Mellitus Tipo 1/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Sistemas de Infusão de Insulina , Insulina/administração & dosagem , Pâncreas Artificial , Adolescente , Adulto , Idoso , Algoritmos , Automonitorização da Glicemia , Diabetes Mellitus Tipo 1/sangue , Feminino , Humanos , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Smartphone , Resultado do Tratamento , Adulto Jovem
11.
Clin Immunol ; 207: 55-57, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30282051

RESUMO

We report a 34-year-old male patient with a novel variant in KMT2D gene, which finally ended a quest for a diagnosis that was clinically suspected in the past, prior the molecular basis of Kabuki Syndrome (KS) was known. The patient showcases the multisystemic features, with involvement of all previously associated with KS body systems, presence of immune deficiency as well as autoimmune disorders, requiring three pancreatic transplants. We also report, for the first time to our knowledge, the presence of epidural lipomatosis and Hodgkin Lymphoma in a patient with KS.

12.
J Endocr Soc ; 2(12): 1320-1337, 2018 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-30474069

RESUMO

The use of personal continuous glucose monitoring (CGM) has expanded dramatically among individuals with diabetes. CGM systems provide retrospective data, as well as the current glucose value and trend arrow data, which indicate the direction and velocity of changing glucose. In 2017, Aleppo and colleagues developed a simplified approach for adults with diabetes to safely adjust rapid-acting insulin doses using trend arrow information in the Dexcom G5 CGM system. Since then, the FreeStyle Libre and FreeStyle Libre 14-day CGM systems have become available in the United States; however, guidance on using trend arrow data that take the unique features of these systems into consideration is lacking. Specifically, the FreeStyle Libre systems do not have automatic alarms, which impact how the system and trend arrow data are used. The Endocrine Society convened an expert panel to address this gap and develop an approach to adjusting rapid-acting insulin doses for adults using trend arrows in the FreeStyle Libre systems. We based our approach on previous work and expanded upon engagement and scanning recommendations, and we incorporated pre-exercise planning specific to these systems. Our approach provides insulin dose adjustments as discrete insulin units based on an individual's insulin sensitivity and directionality of the trend arrow. We focus on the needs of patients treated with multiple daily injections because these individuals currently make up a greater proportion of individuals on intensive insulin therapy. Our recommendations are intended to provide a safe, practical approach to using trend arrows in the FreeStyle Libre systems.

13.
Curr Diab Rep ; 18(10): 88, 2018 08 29.
Artigo em Inglês | MEDLINE | ID: mdl-30159816

RESUMO

PURPOSE OF REVIEW: To provide a current review of closed-loop insulin delivery or artificial pancreas (AP) as therapy for people with type 1 diabetes mellitus (T1D) RECENT FINDINGS: The Medtronic Minimed 670G AP system has been in use in clinical practice since March 2017. Currently, Medtronic is conducting a large randomized clinical trial to evaluate its efficacy further in T1D. Simultaneously, the NIH has funded four research consortia to accelerate progress to approval of other AP and decision support systems. Several research groups are currently developing next-generation AP systems, with a number of companies moving toward releasing closed-loop systems in the future. AP systems are also being tested in select populations such as hypoglycemia-unaware T1D and pregnant T1D. AP research is rapidly advancing. The clinical range of AP will be expanded in the next decade.


Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Sistemas de Infusão de Insulina , Glicemia/metabolismo , Ensaios Clínicos como Assunto , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/terapia , Humanos , Hipoglicemiantes/uso terapêutico , Pâncreas Artificial
14.
Dis Model Mech ; 11(6)2018 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-29915142

RESUMO

High-fat diet (HFD)-fed mouse models have been widely used to study early type 2 diabetes. Decreased ß-cell glucokinase (GCK) expression has been observed in HFD-induced diabetes. However, owing to its crucial roles in glucose metabolism in the liver and in islet ß-cells, the contribution of decreased GCK expression to the development of HFD-induced diabetes is unclear. Here, we employed a ß-cell-targeted gene transfer vector and determined the impact of ß-cell-specific increase in GCK expression on ß-cell function and glucose handling in vitro and in vivo Overexpression of GCK enhanced glycolytic flux, ATP-sensitive potassium channel activation and membrane depolarization, and increased proliferation in Min6 cells. ß-cell-targeted GCK transduction did not change glucose handling in chow-fed C57BL/6 mice. Although adult mice fed a HFD showed reduced islet GCK expression, impaired glucose tolerance and decreased glucose-stimulated insulin secretion (GSIS), ß-cell-targeted GCK transduction improved glucose tolerance and restored GSIS. Islet perifusion experiments verified restored GSIS in isolated HFD islets by GCK transduction. Thus, our data identify impaired ß-cell GCK expression as an underlying mechanism for dysregulated ß-cell function and glycemic control in HFD-induced diabetes. Our data also imply an etiological role of GCK in diet-induced diabetes.This article has an associated First Person interview with the first author of the paper.


Assuntos
Diabetes Mellitus Experimental/enzimologia , Diabetes Mellitus Experimental/patologia , Glucoquinase/metabolismo , Células Secretoras de Insulina/enzimologia , Células Secretoras de Insulina/patologia , Animais , Cálcio/metabolismo , Proliferação de Células , Dependovirus/metabolismo , Diabetes Mellitus Experimental/genética , Dieta Hiperlipídica , Glucose/metabolismo , Teste de Tolerância a Glucose , Glicólise , Insulina/metabolismo , Espaço Intracelular/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Transdução de Sinais , Transdução Genética , Regulação para Cima/genética
15.
Pancreas ; 47(6): 738-741, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29771765

RESUMO

OBJECTIVES: Human pancreatic polypeptide (HPP) is a hormone secreted by the ventral pancreas. While postprandial HPP levels have been studied in chronic pancreatitis (CP) and pancreatic ductal adenocarcinoma (PDAC), there are limited data on fasting HPP in these diseases. METHODS: Fasting serum HPP was measured in the following groups of patients: CP with diabetes mellitus (DM) (n = 16), CP without DM (n = 34), PDAC with new-onset DM (n = 50), PDAC without DM (n = 49), new-onset type 2 DM (n = 50), and controls without DM (n = 49). Sixty-six had type 3c DM (CP with DM, n = 16; PDAC with new-onset DM, n = 50). RESULTS: Median fasting HPP levels (in picograms per milliliter) were similar among all groups. Median (interquartile range) HPP levels in new-onset type 2 DM (n = 50; 288.3 [80.1-1072.1]) were similar to those in type 3c DM (n = 66; 242.3 [64.9-890.9]) (P = 0.71). In PDAC (n = 99), HPP values were similar in pancreatic head (n = 75) versus body/tail (n = 24) tumors (245.3 [64.3-1091.3] vs 334.7 [136.1-841.5]; P = 0.95), regardless of DM. CONCLUSIONS: Fasting HPP levels are similar in CP, PDAC, and controls regardless of glycemic status.


Assuntos
Carcinoma Ductal Pancreático/sangue , Diabetes Mellitus Tipo 2/sangue , Neoplasias Pancreáticas/sangue , Polipeptídeo Pancreático/sangue , Pancreatite Crônica/sangue , Precursores de Proteínas/sangue , Adulto , Idoso , Distribuição de Qui-Quadrado , Ensaio de Imunoadsorção Enzimática/métodos , Jejum/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
16.
Transplantation ; 102(9): 1479-1486, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29528967

RESUMO

ß-cell replacement therapy, available currently as pancreas or islet transplantation, has developed without a clear definition of graft functional and clinical outcomes. The International Pancreas and Islet Transplant Association and European Pancreas and Islet Transplantation Association held a workshop to develop consensus for an International Pancreas and Islet Transplant Association and European Pancreas and Islet Transplant Association Statement on the definition of function and failure of current and future forms of ß-cell replacement therapy. There was consensus that ß-cell replacement therapy could be considered as a treatment for ß-cell failure, regardless of etiology and without requiring undetectable C-peptide, accompanied by glycemic instability with either problematic hypoglycemia or hyperglycemia. Glycemic control should be assessed at a minimum by glycated hemoglobin (HbA1c) and the occurrence of severe hypoglycemia. Optimal ß-cell graft function is defined by near-normal glycemic control (HbA1c ≤6.5% [48 mmol/mol]) without severe hypoglycemia or requirement for insulin or other antihyperglycemic therapy, and with an increase over pretransplant measurement of C-peptide. Good ß-cell graft function requires HbA1c less than 7.0% (53 mmol/mol) without severe hypoglycemia and with a significant (>50%) reduction in insulin requirements and restoration of clinically significant C-peptide production. Marginal ß-cell graft function is defined by failure to achieve HbA1c less than 7.0% (53 mmol/mol), the occurrence of any severe hypoglycemia, or less than 50% reduction in insulin requirements when there is restoration of clinically significant C-peptide production documented by improvement in hypoglycemia awareness/severity, or glycemic variability/lability. A failed ß-cell graft is defined by the absence of any evidence for clinically significant C-peptide production. Optimal and good function are considered successful clinical outcomes.


Assuntos
Diabetes Mellitus/cirurgia , Células Secretoras de Insulina/transplante , Transplante das Ilhotas Pancreáticas/métodos , Biomarcadores/sangue , Glicemia/metabolismo , Peptídeo C/sangue , Consenso , Diabetes Mellitus/sangue , Diabetes Mellitus/diagnóstico , Hemoglobina A Glicada/metabolismo , Humanos , Hipoglicemia/sangue , Hipoglicemia/etiologia , Hipoglicemiantes/uso terapêutico , Células Secretoras de Insulina/metabolismo , Transplante das Ilhotas Pancreáticas/efeitos adversos , Transplante das Ilhotas Pancreáticas/normas , Fatores de Risco , Resultado do Tratamento
17.
J Diabetes Sci Technol ; 12(3): 657-664, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29415563

RESUMO

OBJECTIVE: The objective was to investigate the relationship of body mass index (BMI) to differing glycemic responses to psychological stress in patients with type 1 diabetes. METHODS: Continuous blood glucose monitor (CGM) data were collected for 1 week from a total of 37 patients with BMI ranging from 21.5-39.4 kg/m2 (mean = 28.2 ± 4.9). Patients reported daily stress levels (5-point Likert-type scale, 0 = none, 4 = extreme), physical activity, carbohydrate intake, insulin boluses and basal rates. Daily reported carbohydrates, total insulin bolus, and average blood glucose (BG from CGM) were compared among patients based on their BMI levels on days with different stress levels. In addition, daily averages of a model-based "effectiveness index" (quantifying the combined impact of insulin and carbohydrate on glucose levels) were defined and compared across stress levels to capture meal and insulin independent glycemic changes. RESULTS: Analyses showed that patient BMI likely moderated stress related glycemic changes. Linear mixed effect model results were significant for the stress-BMI interaction on both behavioral and behavior-independent glycemic changes. Across participants, under stress, an increase was observed in daily carbohydrate intake and effectiveness index at higher BMI. There was no significant interactive effect on daily insulin or average BG. CONCLUSION: Findings suggest that (1) stress has both behavioral and nonbehavioral glycemic effects on T1D patients and (2) the direction and magnitude of these effects are potentially influenced by level of stress and patient BMI. Possibly responsible for these observed effects are T1D/BMI related alterations in endocrine response.


Assuntos
Glicemia/análise , Índice de Massa Corporal , Diabetes Mellitus Tipo 1/sangue , Estresse Psicológico/sangue , Adulto , Automonitorização da Glicemia , Diabetes Mellitus Tipo 1/tratamento farmacológico , Feminino , Índice Glicêmico , Humanos , Hipoglicemiantes/administração & dosagem , Insulina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Pâncreas Artificial
18.
Transpl Int ; 31(4): 343-352, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29453879

RESUMO

ß-cell replacement therapy, available currently as pancreas or islet transplantation, has developed without a clear definition of graft functional and clinical outcomes. The International Pancreas & Islet Transplant Association (IPITA) and European Pancreas & Islet Transplantation Association (EPITA) held a workshop to develop consensus for an IPITA/EPITA Statement on the definition of function and failure of current and future forms of ß-cell replacement therapy. There was consensus that ß-cell replacement therapy could be considered as a treatment for ß-cell failure, regardless of etiology and without requiring undetectable C-peptide, accompanied by glycemic instability with either problematic hypoglycemia or hyperglycemia. Glycemic control should be assessed at a minimum by glycated hemoglobin (HbA1c ) and the occurrence of severe hypoglycemia. Optimal ß-cell graft function is defined by near-normal glycemic control [HbA1c  ≤ 6.5% (48 mmol/mol)] without severe hypoglycemia or requirement for insulin or other antihyperglycemic therapy, and with an increase over pretransplant measurement of C-peptide. Good ß-cell graft function requires HbA1c  < 7.0% (53 mmol/mol) without severe hypoglycemia and with a significant (>50%) reduction in insulin requirements and restoration of clinically significant C-peptide production. Marginal ß-cell graft function is defined by failure to achieve HbA1c  < 7.0% (53 mmol/mol), the occurrence of any severe hypoglycemia, or less than 50% reduction in insulin requirements when there is restoration of clinically significant C-peptide production documented by improvement in hypoglycemia awareness/severity, or glycemic variability/lability. A failed ß-cell graft is defined by the absence of any evidence for clinically significant C-peptide production. Optimal and good functional outcomes are considered successful clinical outcomes.


Assuntos
Diabetes Mellitus/cirurgia , Transplante das Ilhotas Pancreáticas , Glicemia , Diabetes Mellitus/sangue , Hemoglobina A Glicada/metabolismo , Humanos
19.
Diabetes Care ; 40(12): 1719-1726, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-29030383

RESUMO

OBJECTIVE: Artificial pancreas (AP) systems are best positioned for optimal treatment of type 1 diabetes (T1D) and are currently being tested in outpatient clinical trials. Our consortium developed and tested a novel adaptive AP in an outpatient, single-arm, uncontrolled multicenter clinical trial lasting 12 weeks. RESEARCH DESIGN AND METHODS: Thirty adults with T1D completed a continuous glucose monitor (CGM)-augmented 1-week sensor-augmented pump (SAP) period. After the AP was started, basal insulin delivery settings used by the AP for initialization were adapted weekly, and carbohydrate ratios were adapted every 4 weeks by an algorithm running on a cloud-based server, with automatic data upload from devices. Adaptations were reviewed by expert study clinicians and patients. The primary end point was change in hemoglobin A1c (HbA1c). Outcomes are reported adhering to consensus recommendations on reporting of AP trials. RESULTS: Twenty-nine patients completed the trial. HbA1c, 7.0 ± 0.8% at the start of AP use, improved to 6.7 ± 0.6% after 12 weeks (-0.3, 95% CI -0.5 to -0.2, P < 0.001). Compared with the SAP run-in, CGM time spent in the hypoglycemic range improved during the day from 5.0 to 1.9% (-3.1, 95% CI -4.1 to -2.1, P < 0.001) and overnight from 4.1 to 1.1% (-3.1, 95% CI -4.2 to -1.9, P < 0.001). Whereas carbohydrate ratios were adapted to a larger extent initially with minimal changes thereafter, basal insulin was adapted throughout. Approximately 10% of adaptation recommendations were manually overridden. There were no protocol-related serious adverse events. CONCLUSIONS: Use of our novel adaptive AP yielded significant reductions in HbA1c and hypoglycemia.


Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Hemoglobina A Glicada/metabolismo , Hipoglicemiantes/administração & dosagem , Insulina/administração & dosagem , Adulto , Glicemia , Automonitorização da Glicemia , Feminino , Humanos , Hipoglicemia/tratamento farmacológico , Sistemas de Infusão de Insulina , Masculino , Pessoa de Meia-Idade , Pâncreas Artificial
20.
ACS Appl Mater Interfaces ; 9(44): 38863-38869, 2017 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-29023095

RESUMO

A novel graphene-based variable capacitor (varactor) that senses glucose based on the quantum capacitance effect was successfully developed. The sensor utilizes a metal-oxide-graphene varactor device structure that is inherently compatible with passive wireless sensing, a key advantage for in vivo glucose sensing. The graphene varactors were functionalized with pyrene-1-boronic acid (PBA) by self-assembly driven by π-π interactions. Successful surface functionalization was confirmed by both Raman spectroscopy and capacitance-voltage characterization of the devices. Through glucose binding to the PBA, the glucose concentration in the buffer solutions modulates the level of electrostatic doping of the graphene surface to different degrees, which leads to capacitance changes and Dirac voltage shifts. These responses to the glucose concentration were shown to be reproducible and reversible over multiple measurement cycles, suggesting promise for eventual use in wireless glucose monitoring.


Assuntos
Glucose/química , Glicemia , Automonitorização da Glicemia , Eletrólitos , Grafite
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