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1.
Diabetes Ther ; 2020 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-32394184

RESUMO

INTRODUCTION: In late February 2020, due to the spread of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the Italian Government closed down all educational and sport activities. In March, it introduced further measures to stop the spread of coronavirus disease (COVID-19), placing the country in a state of almost complete lockdown. We report the impact of these restrictions on glucose control among people with type 1 diabetes (T1D). METHODS: Data were collected on 33 individuals with T1D who were monitoring their glucose levels using a flash glucose monitoring device and remotely connected to the diabetes clinic on a cloud platform. We retrieved information on average glucose, standard deviation and percentage time in hypoglycaemia (< 70 mg/dl), glucose range (70-180 mg/dl) and hyperglycaemia (> 180 mg/dl). We compared glycaemic measures collected during lockdown to those collected before the SARS-CoV-2 epidemic and to the periods immediately before lockdown. RESULTS: In 20 patients who had stopped working and were at home as a result of the lockdown, overall glycaemic control improved during the first 7 days of the lockdown as compared to the weeks before the spread of SARS-CoV-2. Average glucose declined from 177 ± 45 mg/dl (week before lockdown) to 160 ± 40 mg/dl (lockdown; p = 0.005) and the standard deviation improved significantly. Time in range increased from 54.4 to 65.2% (p = 0.010), and time in hyperglycaemia decreased from 42.3 to 31.6% (p = 0.016). The number of scans per day remained unchanged. In 13 patients who continued working, none of the measures of glycaemic control changed during lockdown. CONCLUSION: Despite the limited possibility to exercise and the incumbent psychologic stress, glycaemic control improved in patients with T1D who stopped working during the lockdown, suggesting that slowing down routine daily activities can have beneficial effects on T1D management, at least in the short term.

2.
Diabetes Ther ; : 1-11, 2020 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-32395187

RESUMO

Introduction: In late February 2020, due to the spread of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the Italian Government closed down all educational and sport activities. In March, it introduced further measures to stop the spread of coronavirus disease (COVID-19), placing the country in a state of almost complete lockdown. We report the impact of these restrictions on glucose control among people with type 1 diabetes (T1D). Methods: Data were collected on 33 individuals with T1D who were monitoring their glucose levels using a flash glucose monitoring device and remotely connected to the diabetes clinic on a cloud platform. We retrieved information on average glucose, standard deviation and percentage time in hypoglycaemia (< 70 mg/dl), glucose range (70-180 mg/dl) and hyperglycaemia (> 180 mg/dl). We compared glycaemic measures collected during lockdown to those collected before the SARS-CoV-2 epidemic and to the periods immediately before lockdown. Results: In 20 patients who had stopped working and were at home as a result of the lockdown, overall glycaemic control improved during the first 7 days of the lockdown as compared to the weeks before the spread of SARS-CoV-2. Average glucose declined from 177 ± 45 mg/dl (week before lockdown) to 160 ± 40 mg/dl (lockdown; p = 0.005) and the standard deviation improved significantly. Time in range increased from 54.4 to 65.2% (p = 0.010), and time in hyperglycaemia decreased from 42.3 to 31.6% (p = 0.016). The number of scans per day remained unchanged. In 13 patients who continued working, none of the measures of glycaemic control changed during lockdown. Conclusion: Despite the limited possibility to exercise and the incumbent psychologic stress, glycaemic control improved in patients with T1D who stopped working during the lockdown, suggesting that slowing down routine daily activities can have beneficial effects on T1D management, at least in the short term.

3.
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
4.
J Clin Endocrinol Metab ; 103(3): 1048-1055, 2018 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-29300991

RESUMO

Context: Iatrogenic hypoglycemia is the most common acute diabetic complication, and it significantly increases morbidity. In people with diabetes, reduction in the levels of circulating stem and progenitor cells predicts adverse outcomes. Objective: To evaluate whether hypoglycemia in diabetes affects circulating stem cells and endothelial progenitor cells (EPCs). Design: We performed an experimental hypoglycemia study (Study 1) and a case-control study (Study 2). Setting: Tertiary referral inpatient clinic. Patients and Other Participants: Type 1 diabetic patients (Study 1, n = 19); diabetic patients hospitalized for severe iatrogenic hypoglycemia, matched inpatient and outpatient controls (Study 2, n = 22/group). Interventions: Type 1 diabetic patients underwent two in-hospital sessions of glucose monitoring during a breakfast meal with or without induction of hypoglycemia in random order. In Study 2, patients hospitalized for hypoglycemia and matched controls were compared. Main Outcome Measure: Circulating stem cells and EPCs were measured by flow cytometry based on the expression of CD34 and kinase insert domain receptor (KDR). Results: In Study 1, the physiologic decline of CD34+KDR+ EPCs from 8 am to 2 pm was abolished by insulin-induced hypoglycemia in type 1 diabetic patients. In Study 2, diabetic patients hospitalized for severe iatrogenic hypoglycemia had significantly lower levels of CD34+ stem cells and CD34+KDR+ EPCs compared with diabetic inpatients or outpatient controls. Conclusions: In diabetic patients, a single mild hypoglycemic episode can compromise the physiologic EPC fluctuation, whereas severe hypoglycemia is associated with a marked reduction in stem cells and EPCs. These data provide a possible link between hypoglycemia and adverse outcomes of diabetes.


Assuntos
Diabetes Mellitus Tipo 1/sangue , Células Progenitoras Endoteliais/fisiologia , Hipoglicemia/sangue , Células-Tronco/fisiologia , Adulto , Antígenos CD34/fisiologia , Estudos de Casos e Controles , Diabetes Mellitus Tipo 1/tratamento farmacológico , Feminino , Citometria de Fluxo , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemiantes/efeitos adversos , Insulina/efeitos adversos , Masculino , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/fisiologia
5.
J Clin Endocrinol Metab ; 102(10): 3674-3682, 2017 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-28666360

RESUMO

Context: Closed-loop control (CLC) for the management of type 1 diabetes (T1D) is a novel method for optimizing glucose control, and strategies for individualized implementation are being developed. Objective: To analyze glycemic control in an overnight CLC system designed to "reset" the patient to near-normal glycemic targets every morning. Design: Randomized, crossover, multicenter clinical trial. Participants: Forty-four subjects with T1D requiring insulin pump therapy. Intervention: Sensor-augmented pump therapy (SAP) at home vs 5 nights of CLC (active from 23:00 to 07:00) in a supervised outpatient setting (research house or hotel), with a substudy of 5 nights of CLC subsequently at home. Main Outcome Measure: The percentage of time spent in the target range (70 to 180 mg/dL measured using a continuous glucose monitor). Results: Forty subjects (age, 45.5 ± 9.5 years; hemoglobin A1c, 7.4% ± 0.8%) completed the study. The time in the target range (70 to 180 mg/dL) significantly improved in CLC vs SAP over 24 hours (78.3% vs 71.4%; P = 0.003) and overnight (85.7% vs 67.6%; P < 0.001). The time spent in a hypoglycemic range (<70 mg/dL) decreased significantly in the CLC vs SAP group over 24 hours (2.5% vs 4.3%; P = 0.002) and overnight (0.9% vs 3.2%; P < 0.001). The mean glucose level at 07:00 was lower with CLC than with SAP (123.7 vs 145.3 mg/dL; P < 0.001). The substudy at home, involving 10 T1D subjects, showed similar trends with an increased time in target (70 to 180 mg/dL) overnight (75.2% vs 62.2%; P = 0.07) and decreased time spent in the hypoglycemic range (<70 mg/dL) overnight in CLC vs SAP (0.6% vs 3.7%; P = 0.03). Conclusion: Overnight-only CLC increased the time in the target range over 24 hours and decreased the time in hypoglycemic range over 24 hours in a supervised outpatient setting. A pilot extension study at home showed a similar nonsignificant trend.


Assuntos
Glicemia/efeitos dos fármacos , Ritmo Circadiano , Diabetes Mellitus Tipo 1/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Sistemas de Infusão de Insulina , Insulina/administração & dosagem , Adulto , Glicemia/análise , Automonitorização da Glicemia/instrumentação , Automonitorização da Glicemia/métodos , Ritmo Circadiano/efeitos dos fármacos , Estudos Cross-Over , Diabetes Mellitus Tipo 1/sangue , Feminino , Hemoglobina A Glicada , Humanos , Hipoglicemiantes/efeitos adversos , Insulina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
6.
Diabetes Technol Ther ; 19(1): 18-24, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27982707

RESUMO

BACKGROUND: In the past few years, the artificial pancreas-the commonly accepted term for closed-loop control (CLC) of blood glucose in diabetes-has become a hot topic in research and technology development. In the summer of 2014, we initiated a 6-month trial evaluating the safety of 24/7 CLC during free-living conditions. RESEARCH DESIGN AND METHODS: Following an initial 1-month Phase 1, 14 individuals (10 males/4 females) with type 1 diabetes at three clinical centers in the United States and one in Italy continued with a 5-month Phase 2, which included 24/7 CLC using the wireless portable Diabetes Assistant (DiAs) developed at the University of Virginia Center for Diabetes Technology. Median subject characteristics were age 45 years, duration of diabetes 27 years, total daily insulin 0.53 U/kg/day, and baseline HbA1c 7.2% (55 mmol/mol). RESULTS: Compared with the baseline observation period, the frequency of hypoglycemia below 3.9 mmol/L during the last 3 months of CLC was lower: 4.1% versus 1.3%, P < 0.001. This was accompanied by a downward trend in HbA1c from 7.2% (55 mmol/mol) to 7.0% (53 mmol/mol) at 6 months. HbA1c improvement was correlated with system use (Spearman r = 0.55). The user experience was favorable with identified benefit particularly at night and overall trust in the system. There were no serious adverse events, severe hypoglycemia, or diabetic ketoacidosis. CONCLUSION: We conclude that CLC technology has matured and is safe for prolonged use in patients' natural environment. Based on these promising results, a large randomized trial is warranted to assess long-term CLC efficacy and safety.


Assuntos
Glicemia/análise , Diabetes Mellitus Tipo 1/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Sistemas de Infusão de Insulina , Insulina/administração & dosagem , Adulto , Diabetes Mellitus Tipo 1/sangue , Estudos de Viabilidade , Feminino , Humanos , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Pâncreas Artificial
7.
Diabetes Care ; 39(12): 2158-2164, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27852685

RESUMO

OBJECTIVE: To explore the experiences of children with type 1 diabetes and their parents taking part in an artificial pancreas (AP) clinical trial during a 7-day summer camp. RESEARCH DESIGN AND METHODS: A semistructured interview, composed of 14 questions based on the Technology Acceptance Model, was conducted at the end of the clinical trial. Participants also completed the Diabetes Treatment Satisfaction Questionnaire (DTSQ, parent version) and the AP Acceptance Questionnaire. RESULTS: Thirty children, aged 5-9 years, and their parents completed the study. A content analysis of the interviews showed that parents were focused on understanding the mechanisms, risks, and benefits of the new device, whereas the children were focused on the novelty of the new system. The parents' main concerns about adopting the new system seemed related to the quality of glucose control. The mean scores of DTSQ subscales indicated general parents' satisfaction (44.24 ± 5.99, range 32-53) and trustful views of diabetes control provided by the new system (7.8 ± 2.2, range 3-12). The AP Acceptance Questionnaire revealed that most parents considered the AP easy to use (70.5%), intended to use it long term (94.0%), and felt that it was apt to improve glucose control (67.0%). CONCLUSIONS: Participants manifested a positive attitude toward the AP. Further studies are required to explore participants' perceptions early in the AP development to individualize the new treatment as much as possible, and to tailor it to respond to their needs and values.


Assuntos
Diabetes Mellitus Tipo 1/psicologia , Diabetes Mellitus Tipo 1/terapia , Pâncreas Artificial/psicologia , Pais/psicologia , Adulto , Acampamento , Criança , Pré-Escolar , Diabetes Mellitus Tipo 1/tratamento farmacológico , Feminino , Humanos , Masculino , Relações Pais-Filho , Aceitação pelo Paciente de Cuidados de Saúde , Percepção , Inquéritos e Questionários
8.
Diabetes Care ; 39(7): 1143-50, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27208316

RESUMO

OBJECTIVE: To evaluate the efficacy of a portable, wearable, wireless artificial pancreas system (the Diabetes Assistant [DiAs] running the Unified Safety System) on glucose control at home in overnight-only and 24/7 closed-loop control (CLC) modes in patients with type 1 diabetes. RESEARCH DESIGN AND METHODS: At six clinical centers in four countries, 30 participants 18-66 years old with type 1 diabetes (43% female, 96% non-Hispanic white, median type 1 diabetes duration 19 years, median A1C 7.3%) completed the study. The protocol included a 2-week baseline sensor-augmented pump (SAP) period followed by 2 weeks of overnight-only CLC and 2 weeks of 24/7 CLC at home. Glucose control during CLC was compared with the baseline SAP. RESULTS: Glycemic control parameters for overnight-only CLC were improved during the nighttime period compared with baseline for hypoglycemia (time <70 mg/dL, primary end point median 1.1% vs. 3.0%; P < 0.001), time in target (70-180 mg/dL: 75% vs. 61%; P < 0.001), and glucose variability (coefficient of variation: 30% vs. 36%; P < 0.001). Similar improvements for day/night combined were observed with 24/7 CLC compared with baseline: 1.7% vs. 4.1%, P < 0.001; 73% vs. 65%, P < 0.001; and 34% vs. 38%, P < 0.001, respectively. CONCLUSIONS: CLC running on a smartphone (DiAs) in the home environment was safe and effective. Overnight-only CLC reduced hypoglycemia and increased time in range overnight and increased time in range during the day; 24/7 CLC reduced hypoglycemia and increased time in range both overnight and during the day. Compared with overnight-only CLC, 24/7 CLC provided additional hypoglycemia protection during the day.


Assuntos
Glicemia/análise , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Sistemas de Infusão de Insulina , Insulina/administração & dosagem , Pâncreas Artificial , Smartphone , Adolescente , Adulto , Idoso , Glicemia/efeitos dos fármacos , Automonitorização da Glicemia/instrumentação , Automonitorização da Glicemia/métodos , Feminino , Humanos , Hipoglicemia/prevenção & controle , Hipoglicemiantes/efeitos adversos , Insulina/efeitos adversos , Internacionalidade , Masculino , Pessoa de Meia-Idade , Aplicativos Móveis , Pâncreas Artificial/efeitos adversos , Adulto Jovem
9.
Diabetes Care ; 39(7): 1151-60, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27208331

RESUMO

OBJECTIVE: After testing of a wearable artificial pancreas (AP) during evening and night (E/N-AP) under free-living conditions in patients with type 1 diabetes (T1D), we investigated AP during day and night (D/N-AP) for 1 month. RESEARCH DESIGN AND METHODS: Twenty adult patients with T1D who completed a previous randomized crossover study comparing 2-month E/N-AP versus 2-month sensor augmented pump (SAP) volunteered for 1-month D/N-AP nonrandomized extension. AP was executed by a model predictive control algorithm run by a modified smartphone wirelessly connected to a continuous glucose monitor (CGM) and insulin pump. CGM data were analyzed by intention-to-treat with percentage time-in-target (3.9-10 mmol/L) over 24 h as the primary end point. RESULTS: Time-in-target (mean ± SD, %) was similar over 24 h with D/N-AP versus E/N-AP: 64.7 ± 7.6 vs. 63.6 ± 9.9 (P = 0.79), and both were higher than with SAP: 59.7 ± 9.6 (P = 0.01 and P = 0.06, respectively). Time below 3.9 mmol/L was similarly and significantly reduced by D/N-AP and E/N-AP versus SAP (both P < 0.001). SD of blood glucose concentration (mmol/L) was lower with D/N-AP versus E/N-AP during whole daytime: 3.2 ± 0.6 vs. 3.4 ± 0.7 (P = 0.003), morning: 2.7 ± 0.5 vs. 3.1 ± 0.5 (P = 0.02), and afternoon: 3.3 ± 0.6 vs. 3.5 ± 0.8 (P = 0.07), and was lower with D/N-AP versus SAP over 24 h: 3.1 ± 0.5 vs. 3.3 ± 0.6 (P = 0.049). Insulin delivery (IU) over 24 h was higher with D/N-AP and SAP than with E/N-AP: 40.6 ± 15.5 and 42.3 ± 15.5 vs. 36.6 ± 11.6 (P = 0.03 and P = 0.0004, respectively). CONCLUSIONS: D/N-AP and E/N-AP both achieved better glucose control than SAP under free-living conditions. Although time in the different glycemic ranges was similar between D/N-AP and E/N-AP, D/N-AP further reduces glucose variability.


Assuntos
Glicemia/análise , Ritmo Circadiano/fisiologia , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/tratamento farmacológico , Sistemas de Infusão de Insulina , Insulina/administração & dosagem , Pâncreas Artificial , Adulto , Algoritmos , Glicemia/efeitos dos fármacos , Automonitorização da Glicemia/métodos , Estudos Cross-Over , Estudos de Viabilidade , Feminino , Humanos , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/efeitos adversos , Insulina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Condições Sociais , Adulto Jovem
10.
Diabetes Care ; 39(7): 1180-5, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27208335

RESUMO

OBJECTIVE: The Pediatric Artificial Pancreas (PedArPan) project tested a children-specific version of the modular model predictive control (MMPC) algorithm in 5- to 9-year-old children during a camp. RESEARCH DESIGN AND METHODS: A total of 30 children, 5- to 9-years old, with type 1 diabetes completed an outpatient, open-label, randomized, crossover trial. Three days with an artificial pancreas (AP) were compared with three days of parent-managed sensor-augmented pump (SAP). RESULTS: Overnight time-in-hypoglycemia was reduced with the AP versus SAP, median (25(th)-75(th) percentiles): 0.0% (0.0-2.2) vs. 2.2% (0.0-12.3) (P = 0.002), without a significant change of time-in-target, mean: 56.0% (SD 22.5) vs. 59.7% (21.2) (P = 0.430), but with increased mean glucose 173 mg/dL (36) vs. 150 mg/dL (39) (P = 0.002). Overall, the AP granted a threefold reduction of time-in-hypoglycemia (P < 0.001) at the cost of decreased time-in-target, 56.8% (13.5) vs. 63.1% (11.0) (P = 0.022) and increased mean glucose 169 mg/dL (23) vs. 147 mg/dL (23) (P < 0.001). CONCLUSIONS: This trial, the first outpatient single-hormone AP trial in a population of this age, shows feasibility and safety of MMPC in young children. Algorithm retuning will be performed to improve efficacy.


Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Pâncreas Artificial , Algoritmos , Glicemia/análise , Criança , Pré-Escolar , Estudos Cross-Over , Estudos de Viabilidade , Feminino , Humanos , Hipoglicemia/epidemiologia , Hipoglicemia/prevenção & controle , Sistemas de Infusão de Insulina , Masculino
11.
Lancet Diabetes Endocrinol ; 3(12): 939-47, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26432775

RESUMO

BACKGROUND: An artificial pancreas (AP) that can be worn at home from dinner to waking up in the morning might be safe and efficient for first routine use in patients with type 1 diabetes. We assessed the effect on glucose control with use of an AP during the evening and night plus patient-managed sensor-augmented pump therapy (SAP) during the day, versus 24 h use of patient-managed SAP only, in free-living conditions. METHODS: In a crossover study done in medical centres in France, Italy, and the Netherlands, patients aged 18-69 years with type 1 diabetes who used insulin pumps for continuous subcutaneous insulin infusion were randomly assigned to 2 months of AP use from dinner to waking up plus SAP use during the day versus 2 months of SAP use only under free-living conditions. Randomisation was achieved with a computer-generated allocation sequence with random block sizes of two, four, or six, masked to the investigator. Patients and investigators were not masked to the type of intervention. The AP consisted of a continuous glucose monitor (CGM) and insulin pump connected to a modified smartphone with a model predictive control algorithm. The primary endpoint was the percentage of time spent in the target glucose concentration range (3·9-10·0 mmol/L) from 2000 to 0800 h. CGM data for weeks 3-8 of the interventions were analysed on a modified intention-to-treat basis including patients who completed at least 6 weeks of each intervention period. The 2 month study period also allowed us to asses HbA1c as one of the secondary outcomes. This trial is registered with ClinicalTrials.gov, number NCT02153190. FINDINGS: During 2000-0800 h, the mean time spent in the target range was higher with AP than with SAP use: 66·7% versus 58·1% (paired difference 8·6% [95% CI 5·8 to 11·4], p<0·0001), through a reduction in both mean time spent in hyperglycaemia (glucose concentration >10·0 mmol/L; 31·6% vs 38·5%; -6·9% [-9·8% to -3·9], p<0·0001) and in hypoglycaemia (glucose concentration <3·9 mmol/L; 1·7% vs 3·0%; -1·6% [-2·3 to -1·0], p<0·0001). Decrease in mean HbA1c during the AP period was significantly greater than during the control period (-0·3% vs -0·2%; paired difference -0·2 [95% CI -0·4 to -0·0], p=0·047), taking a period effect into account (p=0·0034). No serious adverse events occurred during this study, and none of the mild-to-moderate adverse events was related to the study intervention. INTERPRETATION: Our results support the use of AP at home as a safe and beneficial option for patients with type 1 diabetes. The HbA1c results are encouraging but preliminary. FUNDING: European Commission.


Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Hiperglicemia/prevenção & controle , Hipoglicemia/prevenção & controle , Hipoglicemiantes/administração & dosagem , Insulina/administração & dosagem , Pâncreas Artificial , Adolescente , Adulto , Idoso , Glicemia/metabolismo , Automonitorização da Glicemia , Estudos Cross-Over , Diabetes Mellitus Tipo 1/sangue , Feminino , Humanos , Sistemas de Infusão de Insulina , Masculino , Pessoa de Meia-Idade , Monitorização Fisiológica , Smartphone , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
12.
Diabetes Technol Ther ; 17(3): 203-9, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25594434

RESUMO

BACKGROUND: Studies of closed-loop control (CLC) systems have improved glucose levels in patients with type 1 diabetes. In this study we test a new CLC concept aiming to "reset" the patient overnight to near-normoglycemia each morning, for several consecutive nights. SUBJECTS AND METHODS: Ten insulin pump users with type 1 diabetes (mean age, 46.4±8.5 years) were enrolled in a two-center (in the United States and Italy) randomized crossover trial comparing 5 consecutive nights of CLC (23:00-07:00 h) in an outpatient setting versus sensor-augmented insulin pump therapy of the same duration at home. Primary end points included time spent in 80-140 mg/dL as measured by continuous glucose monitoring overnight and fasting blood glucose distribution at 7:00 h. RESULTS: Compared with sensor-augmented pump therapy, CLC improved significantly time spent between 80 and 140 mg/dL (54.5% vs. 32.2%; P<0.001) and between 70 and 180 mg/dL (85.4% vs. 59.1%; P<0.001); CLC reduced the mean glucose level at 07:00 h (119.3 vs. 152.9 mg/dL; P<0.001) and overnight mean glucose level (139.0 vs. 170.3 mg/dL; P<0.001) using a marginally lower amount of insulin (6.1 vs. 6.8 units; P=0.1). Tighter overnight control led to improved daytime control on the next day: the overnight/next-day control correlation was r=0.52, P<0.01. CONCLUSIONS: Multinight CLC of insulin delivery (artificial pancreas) results in significant improvement in morning and overnight glucose levels and time in target range, with the potential to improve daytime control when glucose levels were "reset" to near-normoglycemia each morning.


Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Cronoterapia Farmacológica , Hipoglicemiantes/administração & dosagem , Sistemas de Infusão de Insulina , Insulina/administração & dosagem , Adulto , Glicemia/metabolismo , Automonitorização da Glicemia/métodos , Automonitorização da Glicemia/estatística & dados numéricos , Estudos Cross-Over , Diabetes Mellitus Tipo 1/sangue , Jejum/sangue , Feminino , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Resultado do Tratamento , Estados Unidos
13.
Vascul Pharmacol ; 67-69: 21-9, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25483979

RESUMO

Type 2 diabetes (T2D) is characterized by impaired vascular regeneration owing to reduced endothelial progenitor cells (EPCs). While statins are known to increase EPCs, the effects of statin withdrawal on EPCs are unknown. Herein, we evaluated the effects of statin discontinuation on EPCs, inflammation and in vivo angiogenesis. Thirty-four T2D patients were randomized to 5-day discontinuation or continuation of statin treatment. At baseline and at day 5, we determined lipid profile, EPC levels, monocyte-macrophage polarization, and concentrations of hsCRP, VEGF, SDF-1α, and G-CSF. Angiogenesis by human circulating cells was assessed in vivo. At day 5, patients who stopped statins showed raised total and LDL cholesterol and EPCs compared to baseline, while no changes were observed in patients who continued statins. No changes were observed in hsCRP, VEGF, SDF-1α, G-CSF, M1 and M2 macrophages and classical, intermediate and nonclassical monocytes in both groups. In vivo angiogenesis by circulating cells was increased in patients who stopped statin treatment. In vitro, cholesterol supplementation stimulated mobilizing signals in human bone marrow mesenchymal stem cells. In conclusion, a brief statin withdrawal increases circulating EPCs and functional proangiogenic cells in T2D. These findings identify statin-sensitive pathways as reverse target mechanisms to stimulate vascular repair in diabetes.


Assuntos
Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Células Progenitoras Endoteliais/efeitos dos fármacos , Células Progenitoras Endoteliais/metabolismo , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Células Cultivadas , LDL-Colesterol/sangue , Esquema de Medicação , Feminino , Humanos , Inflamação/sangue , Inflamação/diagnóstico , Masculino , Camundongos , Camundongos Knockout , Pessoa de Meia-Idade , Fatores de Tempo
14.
Diabetologia ; 57(9): 1947-56, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24962668

RESUMO

AIMS/HYPOTHESIS: Chronic foot ulceration is a severe complication of diabetes, driving morbidity and mortality. The mechanisms underlying delaying wound healing in diabetes are incompletely understood and tools to identify such pathways are eagerly awaited. METHODS: Wound biopsies were obtained from 75 patients with diabetic foot ulcers. Matched subgroups of rapidly healing (RH, n = 17) and non-healing (NH, n = 11) patients were selected. Proteomic analysis was performed by labelling with isobaric tag for relative and absolute quantification and mass spectrometry. Differentially expressed proteins were analysed in NH vs RH for identification of pathogenic pathways. Individual sample gene/protein validation and in vivo validation of candidate pathways in mouse models were carried out. RESULTS: Pathway analyses were conducted on 92/286 proteins that were differentially expressed in NH vs RH. The following pathways were enriched in NH vs RH patients: apoptosis, protease inhibitors, epithelial differentiation, serine endopeptidase activity, coagulation and regulation of defence response. SerpinB3 was strongly upregulated in RH vs NH wounds, validated as protein and mRNA in individual samples. To test the relevance of serpinB3 in vivo, we used a transgenic mouse model with α1-antitrypsin promoter-driven overexpression of human SERPINB3. In this model, wound healing was unaffected by SERPINB3 overexpression in non-diabetic or diabetic mice with or without hindlimb ischaemia. In an independent validation cohort of 47 patients, high serpinB3 protein content was confirmed as a biomarker of healing improvement. CONCLUSIONS/INTERPRETATION: We provide a benchmark for the unbiased discovery of novel molecular targets and biomarkers of impaired diabetic wound healing. High serpinB3 protein content was found to be a biomarker of successful healing in diabetic patients.


Assuntos
Antígenos de Neoplasias/metabolismo , Biomarcadores/metabolismo , Pé Diabético/metabolismo , Pé Diabético/fisiopatologia , Serpinas/metabolismo , Cicatrização/fisiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Antígenos de Neoplasias/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Serpinas/genética , Adulto Jovem
15.
Diabetes Care ; 37(7): 1789-96, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24929429

RESUMO

OBJECTIVE: We estimate the effect size of hypoglycemia risk reduction on closed-loop control (CLC) versus open-loop (OL) sensor-augmented insulin pump therapy in supervised outpatient setting. RESEARCH DESIGN AND METHODS: Twenty patients with type 1 diabetes initiated the study at the Universities of Virginia, Padova, and Montpellier and Sansum Diabetes Research Institute; 18 completed the entire protocol. Each patient participated in two 40-h outpatient sessions, CLC versus OL, in randomized order. Sensor (Dexcom G4) and insulin pump (Tandem t:slim) were connected to Diabetes Assistant (DiAs)-a smartphone artificial pancreas platform. The patient operated the system through the DiAs user interface during both CLC and OL; study personnel supervised on site and monitored DiAs remotely. There were no dietary restrictions; 45-min walks in town and restaurant dinners were included in both CLC and OL; alcohol was permitted. RESULTS: The primary outcome-reduction in risk for hypoglycemia as measured by the low blood glucose (BG) index (LGBI)-resulted in an effect size of 0.64, P = 0.003, with a twofold reduction of hypoglycemia requiring carbohydrate treatment: 1.2 vs. 2.4 episodes/session on CLC versus OL (P = 0.02). This was accompanied by a slight decrease in percentage of time in the target range of 3.9-10 mmol/L (66.1 vs. 70.7%) and increase in mean BG (8.9 vs. 8.4 mmol/L; P = 0.04) on CLC versus OL. CONCLUSIONS: CLC running on a smartphone (DiAs) in outpatient conditions reduced hypoglycemia and hypoglycemia treatments when compared with sensor-augmented pump therapy. This was accompanied by marginal increase in average glycemia resulting from a possible overemphasis on hypoglycemia safety.


Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Insulina/administração & dosagem , Pâncreas Artificial , Adulto , Glicemia/efeitos dos fármacos , Automonitorização da Glicemia , Telefone Celular , Estudos Cross-Over , Diabetes Mellitus Tipo 1/sangue , Feminino , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemiantes/efeitos adversos , Hipoglicemiantes/uso terapêutico , Insulina/efeitos adversos , Insulina/uso terapêutico , Sistemas de Infusão de Insulina , Masculino , Pessoa de Meia-Idade , Pacientes Ambulatoriais , Pâncreas Artificial/efeitos adversos , Resultado do Tratamento
16.
Am J Physiol Heart Circ Physiol ; 301(2): H592-8, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21572012

RESUMO

The metabolic syndrome (MS), a predisposing condition for cardiovascular disease, presents disturbances in hemodynamics; impedance cardiography (ICG) can assess these alterations. In subjects with MS, the morphology of the pulses present in the ICG time series is more irregular/complex than in normal subjects. Therefore, the aim of the present study was to quantitatively assess the complexity of ICG times series in 53 patients, with or without MS, through a nonlinear analysis algorithm, the approximate entropy, a method employed in recent years for the study of several biological signals, which provides a scalar index, ApEn. We correlated ApEn computed from ICG times series data during fasting and postprandial phase with the presence of alterations in the parameters defining MS [Adult Treatment Panel (ATP) III (Grundy SM, Brewer HB Jr, Cleeman JI, Smith SC Jr, Lenfant C; National Heart, Lung, and Blood Institute; American Heart Association. Circulation 109: 433-438, 2004) and the International Diabetes Federation (IDF) definition]. Results show that ApEn was significantly higher in subjects with MS compared with those without (1.81 ± 0.09 vs. 1.65 ± 0.13; means ± SD; P = 0.0013, with ATP III definition; 1.82 ± 0.09 vs. 1.67 ± 0.12; P = 0.00006, with the IDF definition). We also demonstrated that ApEn increase parallels the number of components of MS. ApEn was then correlated to each MS component: mean ApEn values of subjects belonging to the first and fourth quartiles of the distribution of MS parameters were statistically different for all parameters but HDL cholesterol. No difference was observed between ApEn values evaluated in fasting and postprandial states. In conclusion, we identified that MS is characterized by an increased complexity of ICG signals: this may have a prognostic relevance in subjects with this condition.


Assuntos
Cardiografia de Impedância , Hemodinâmica , Síndrome Metabólica/fisiopatologia , Processamento de Sinais Assistido por Computador , Adulto , Algoritmos , Análise de Variância , Estudos de Casos e Controles , Jejum/sangue , Feminino , Humanos , Masculino , Síndrome Metabólica/sangue , Pessoa de Meia-Idade , Dinâmica não Linear , Período Pós-Prandial , Valor Preditivo dos Testes , Fatores de Tempo
17.
Am J Clin Nutr ; 93(5): 926-33, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21411620

RESUMO

BACKGROUND: In the postprandial state, insulin regulates metabolic and cardiovascular responses. In insulin resistance, the insulin action is impaired at both levels. However, postprandial hemodynamic responses are poorly characterized in this setting. OBJECTIVE: We investigated fasting and postprandial cardiac and vascular hemodynamic responses in subjects with and without insulin resistance. DESIGN: Sixty-six atherosclerosis-free, healthy volunteers were studied in a fasted state and ≤180 min after ingestion of a mixed meal. The insulin sensitivity index was determined by using a minimal model analysis; hemodynamic response was monitored by using continuous impedance cardiography that allowed a reliable beat-to-beat noninvasive evaluation of stroke volume, cardiac contractility, and several derived variables. RESULTS: Subjects were divided into insulin-resistant (IR; n = 33) and insulin-sensitive (IS; n = 33) groups. After fasting, IR subjects had significantly higher values of systolic and diastolic blood pressures and the systemic vascular resistance index (SVRI) than did IS subjects. In the postprandial state, acute vasodilatation was comparable and synchronous (at 30 min) in IR and IS subjects (P = 0.209), but subsequent vascular tone recovery (30-180 min) was significantly impaired in IR subjects (P = 0.018), even after adjustment for age and sex (P = 0.031). Hemodynamic dysregulation was directly correlated with metabolic disturbances in the postprandial state. In basal and postprandial states, hemodynamic variables related to cardiac function were not significantly different in IR and IS subjects. CONCLUSIONS: IR subjects had a worse fasting vascular performance than did IS subjects. In the postprandial phase, insulin resistance was associated with a shorter duration of vasodilatation in the absence of an altered cardiac performance. Peripheral hemodynamic alterations in fasting and postprandial states may have a negative effect on cardiovascular performance in IR patients.


Assuntos
Ingestão de Alimentos , Hemodinâmica , Resistência à Insulina , Adulto , Glicemia/análise , Pressão Sanguínea , Peptídeo C/sangue , Cardiografia de Impedância , Doenças Cardiovasculares/fisiopatologia , Estudos Transversais , Feminino , Humanos , Insulina/sangue , Cinética , Masculino , Pessoa de Meia-Idade , Período Pós-Prandial , Resistência Vascular , Vasodilatação
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