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1.
Diabetes Technol Ther ; 22(3): 174-184, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31596130

RESUMO

Background: The objective of this study was to assess the safety and performance of the Omnipod® personalized model predictive control (MPC) algorithm in adults, adolescents, and children aged ≥6 years with type 1 diabetes (T1D) under free-living conditions using an investigational device. Materials and Methods: A 96-h hybrid closed-loop (HCL) study was conducted in a supervised hotel/rental home setting following a 7-day outpatient standard therapy (ST) phase. Eligible participants were aged 6-65 years with A1C <10.0% using insulin pump therapy or multiple daily injections. Meals during HCL were unrestricted, with boluses administered per usual routine. There was daily physical activity. The primary endpoints were percentage of time with sensor glucose <70 and ≥250 mg/dL. Results: Participants were 11 adults, 10 adolescents, and 15 children aged (mean ± standard deviation) 28.8 ± 7.9, 14.3 ± 1.3, and 9.9 ± 1.0 years, respectively. Percentage time ≥250 mg/dL during HCL was 4.5% ± 4.2%, 3.5% ± 5.0%, and 8.6% ± 8.8% per respective age group, a 1.6-, 3.4-, and 2.0-fold reduction compared to ST (P = 0.1, P = 0.02, and P = 0.03). Percentage time <70 mg/dL during HCL was 1.9% ± 1.3%, 2.5% ± 2.0%, and 2.2% ± 1.9%, a statistically significant decrease in adults when compared to ST (P = 0.005, P = 0.3, and P = 0.3). Percentage time 70-180 mg/dL increased during HCL compared to ST, reaching significance for adolescents and children: HCL 73.7% ± 7.5% vs. ST 68.0% ± 15.6% for adults (P = 0.08), HCL 79.0% ± 12.6% vs. ST 60.6% ± 13.4% for adolescents (P = 0.01), and HCL 69.2% ± 13.5% vs. ST 54.9% ± 12.9% for children (P = 0.003). Conclusions: The Omnipod personalized MPC algorithm was safe and performed well over 5 days and 4 nights of use by a cohort of participants ranging from youth aged ≥6 years to adults with T1D under supervised free-living conditions with challenges, including daily physical activity and unrestricted meals.

2.
Diabetes Technol Ther ; 21(3): 101-104, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30688521

RESUMO

OBJECTIVE: We have shown that "euglycemic DKA" in patients with type 1 diabetes receiving a sodium-glucose cotransporter 2-inhibitor (SGLT2i) is due to normal increases in rates of ketogenesis but blunted increases in plasma glucose levels. In this analysis, we assessed whether rescue treatment of early ketoacidosis with insulin is altered by SGLT2i use. RESEARCH DESIGN AND METHODS: Participants received 0.2 U/kg of aspart insulin after two 6-h interruptions of basal insulin that increased beta-hydroxybutyrate (BHB) by 1.2 ± 0.7 mmol/L before and by 1.5 ± 0.2 mmol/L during canagliflozin treatment. BHB and free fatty acid (FFA) were monitored every 30 min for 120 min after receiving a 0.2 U/kg subcutaneous injection of aspart insulin. RESULTS: Ten adults (23 ± 5 years) were studied. During the 120 min after rescue therapy with insulin, the reductions in BHB and FFA were nearly identical between the pre- and during canagliflozin treatment studies, respectively (-1.27 ± 0.76 and -1.13 ± 0.69, P = 0.671 for BHB and -0.50 ± 0.35 vs. -0.41 ± 0.41, P = 0.603 for FFA). CONCLUSION: These data indicate that turning ketogenesis off, as well as on, does not appear to be affected by SGLT2i use.


Assuntos
Canagliflozina/administração & dosagem , Diabetes Mellitus Tipo 1/complicações , Cetoacidose Diabética/tratamento farmacológico , Insulina Aspart/administração & dosagem , Inibidores do Transportador 2 de Sódio-Glicose/administração & dosagem , Ácido 3-Hidroxibutírico/sangue , Adulto , Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 1/tratamento farmacológico , Cetoacidose Diabética/sangue , Ácidos Graxos não Esterificados/sangue , Feminino , Humanos , Masculino , Resultado do Tratamento
3.
Diabetes Care ; 41(10): 2155-2161, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30089663

RESUMO

OBJECTIVE: This study evaluated a new insulin delivery system designed to reduce insulin delivery when trends in continuous glucose monitoring (CGM) glucose concentrations predict future hypoglycemia. RESEARCH DESIGN AND METHODS: Individuals with type 1 diabetes (n = 103, age 6-72 years, mean HbA1c 7.3% [56 mmol/mol]) participated in a 6-week randomized crossover trial to evaluate the efficacy and safety of a Tandem Diabetes Care t:slim X2 pump with Basal-IQ integrated with a Dexcom G5 sensor and a predictive low-glucose suspend algorithm (PLGS) compared with sensor-augmented pump (SAP) therapy. The primary outcome was CGM-measured time <70 mg/dL. RESULTS: Both study periods were completed by 99% of participants; median CGM usage exceeded 90% in both arms. Median time <70 mg/dL was reduced from 3.6% at baseline to 2.6% during the 3-week period in the PLGS arm compared with 3.2% in the SAP arm (difference [PLGS - SAP] = -0.8%, 95% CI -1.1 to -0.5, P < 0.001). The corresponding mean values were 4.4%, 3.1%, and 4.5%, respectively, represent-ing a 31% reduction in the time <70 mg/dL with PLGS. There was no increase in mean glucose concentration (159 vs. 159 mg/dL, P = 0.40) or percentage of time spent >180 mg/dL (32% vs. 33%, P = 0.12). One severe hypoglycemic event occurred in the SAP arm and none in the PLGS arm. Mean pump suspension time was 104 min/day. CONCLUSIONS: The Tandem Diabetes Care Basal-IQ PLGS system significantly reduced hypoglycemia without rebound hyperglycemia, indicating that the system can benefit adults and youth with type 1 diabetes in improving glycemic control.


Assuntos
Automonitorização da Glicemia , Diabetes Mellitus Tipo 1/tratamento farmacológico , Hipoglicemia/prevenção & controle , Hipoglicemiantes/administração & dosagem , Sistemas de Infusão de Insulina , Insulina/administração & dosagem , Adolescente , Adulto , Idoso , Algoritmos , Glicemia/análise , Automonitorização da Glicemia/métodos , Criança , Estudos Cross-Over , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/diagnóstico , Sistemas de Liberação de Medicamentos , Feminino , Humanos , Hipoglicemia/sangue , Hipoglicemia/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Monitorização Ambulatorial , Adulto Jovem
4.
J Clin Endocrinol Metab ; 103(3): 1088-1094, 2018 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-29211871

RESUMO

Context: Postprandial hyperglycemia remains a challenge in type 1 diabetes (T1D) due, in part, to dysregulated increases in plasma glucagon levels after meals. Objective: This study was undertaken to examine whether 3 to 4 weeks of therapy with pramlintide or liraglutide might help to blunt postprandial hyperglycemia in T1D by suppressing plasma glucagon responses to mixed-meal feedings. Design: Two parallel studies were conducted in which participants underwent mixed-meal tolerance tests (MMTTs) without premeal bolus insulin administration before and after 3 to 4 weeks of treatment with either pramlintide (8 participants aged 20 ± 3 years, hemoglobin A1c 6.9 ± 0.5%) or liraglutide (10 participants aged 22 ± 3 years, hemoglobin A1c 7.6 ± 0.9%). Results: Compared with pretreatment responses to the MMTT, treatment with pramlintide reduced the peak increment in glucagon from 32 ± 16 to 23 ± 12 pg/mL (P < 0.02). In addition, the incremental area under the plasma glucagon curve from 0 to 120 minutes dropped from 1988 ± 590 to 737 ± 577 pg/mL/min (P < 0.001), which was accompanied by a similar reduction in the meal-stimulated increase in the plasma glucose curve from 11,963 ± 1424 mg/dL/min pretreatment vs 2493 ± 1854 mg/dL/min after treatment (P < 0.01). In contrast, treatment with liraglutide had no effect on plasma glucagon and glucose responses during the MMTT. Conclusions: Adjunctive treatment with pramlintide may provide an effective means to blunt postmeal hyperglycemia in T1D by suppressing dysregulated plasma glucagon responses. In contrast, plasma glucose and glucagon responses were unchanged after 3 to 4 weeks of treatment with liraglutide.


Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Hiperglicemia/prevenção & controle , Hipoglicemiantes/administração & dosagem , Polipeptídeo Amiloide das Ilhotas Pancreáticas/administração & dosagem , Liraglutida/administração & dosagem , Adolescente , Adulto , Glicemia/análise , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/complicações , Feminino , Glucagon/sangue , Hemoglobina A Glicada/análise , Humanos , Hiperglicemia/etiologia , Masculino , Refeições/fisiologia , Período Pós-Prandial/efeitos dos fármacos , Resultado do Tratamento , Adulto Jovem
5.
Diabetes Technol Ther ; 19(11): 618-622, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-29068709

RESUMO

BACKGROUND: Enthusiasm for the benefits of sodium-glucose cotransporter 2 inhibitors (SGLT2i) as an adjunctive treatment in type 1 diabetes (T1D) has been offset by the possible increased risk of diabetic ketoacidosis (DKA). Since pump-treated T1D patients are susceptible to DKA due to infusion site problems, this study was undertaken to assess how treatment with SGLT2i affects patterns of early metabolic decompensation following suspension of basal insulin. METHODS: Ten T1D participants (age 19-35 years, duration 10 ± 8 years, A1c 7.4% ± 0.8%) underwent overnight pump suspension studies before and after treatment with canagliflozin (CANA). On both nights, basal insulin was suspended at 3 AM and plasma glucose (PG), ß-hydroxybutyrate (BHB), free fatty acids (FFA), plasma insulin (PI), and glucagon were measured. Studies were terminated 6 h after suspension or if PG rose to >350 mg/dL or BHB >2.5 mmol/L. RESULTS: PI levels at the start of suspension were reduced by 30% after CANA treatment (44 ± 11 uU/mL vs. 31 ± 10 uU/mL, P < 0.01), but baseline PG, BHB, FFA, and glucagon levels were not significantly different. During the suspension, PG rose from 104 ± 10 to 301 ± 21 mg/dL before treatment, but only from 109 ± 8 to 195 ± 14 mg/dL after treatment (P = 0.002 vs. pretreatment values). On the other hand, CANA treatment did not significantly affect the magnitude of increases in FFA, BHB, and glucagon levels during the suspension study. CONCLUSION: These data indicate that SGLT2i do not accelerate the rate of ketogenesis following the interruption of basal insulin infusion in T1D. Rather, the failure of patients to promptly recognize early metabolic decompensation relates to the much more gradual rise in PG levels.


Assuntos
Glicemia/análise , Canagliflozina/uso terapêutico , Diabetes Mellitus Tipo 1/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Insulina/sangue , Inibidores do Transportador 2 de Sódio-Glicose , Adolescente , Adulto , Canagliflozina/administração & dosagem , Diabetes Mellitus Tipo 1/sangue , Ácidos Graxos não Esterificados/sangue , Feminino , Glucagon/sangue , Humanos , Hipoglicemiantes/administração & dosagem , Insulina/administração & dosagem , Sistemas de Infusão de Insulina , Masculino , Pessoa de Meia-Idade , Adulto Jovem
6.
Pediatr Diabetes ; 18(5): 348-355, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-27191182

RESUMO

BACKGROUND: Automated insulin delivery systems, utilizing a control algorithm to dose insulin based upon subcutaneous continuous glucose sensor values and insulin pump therapy, will soon be available for commercial use. The objective of this study was to determine the preliminary safety and efficacy of initialization parameters with the Medtronic hybrid closed-loop controller by comparing percentage of time in range, 70-180 mg/dL (3.9-10 mmol/L), mean glucose values, as well as percentage of time above and below target range between sensor-augmented pump therapy and hybrid closed-loop, in adults and adolescents with type 1 diabetes. METHODS: We studied an initial cohort of 9 adults followed by a second cohort of 15 adolescents, using the Medtronic hybrid closed-loop system with the proportional-integral-derivative with insulin feed-back (PID-IFB) algorithm. Hybrid closed-loop was tested in supervised hotel-based studies over 4-5 days. RESULTS: The overall mean percentage of time in range (70-180 mg/dL, 3.9-10 mmol/L) during hybrid closed-loop was 71.8% in the adult cohort and 69.8% in the adolescent cohort. The overall percentage of time spent under 70 mg/dL (3.9 mmol/L) was 2.0% in the adult cohort and 2.5% in the adolescent cohort. Mean glucose values were 152 mg/dL (8.4 mmol/L) in the adult cohort and 153 mg/dL (8.5 mmol/L) in the adolescent cohort. CONCLUSIONS: Closed-loop control using the Medtronic hybrid closed-loop system enables adaptive, real-time basal rate modulation. Initializing hybrid closed-loop in clinical practice will involve individualizing initiation parameters to optimize overall glucose control.


Assuntos
Atividades Cotidianas , Diabetes Mellitus Tipo 1/tratamento farmacológico , Glucose/metabolismo , Hiperglicemia/prevenção & controle , Pâncreas Artificial , Medicina de Precisão , Tela Subcutânea/efeitos dos fármacos , Adolescente , Comportamento do Adolescente , Adulto , Algoritmos , Glicemia/análise , Automonitorização da Glicemia , Calibragem , Estudos de Coortes , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/metabolismo , Cálculos da Dosagem de Medicamento , Monitoramento de Medicamentos , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemia/prevenção & controle , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/efeitos adversos , Hipoglicemiantes/uso terapêutico , Insulina/administração & dosagem , Insulina/efeitos adversos , Insulina/uso terapêutico , Pâncreas Artificial/efeitos adversos , Tela Subcutânea/metabolismo , Adulto Jovem
7.
Diabetes Technol Ther ; 18(12): 794-799, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27996320

RESUMO

OBJECTIVE: To assess whether snacking could be used with closed-loop (CL) insulin delivery to avoid exercise-induced reductions in plasma glucose (PG), as well as elevations in PG at the end of exercise. RESEARCH DESIGN AND METHODS: Twelve type 1 diabetes (T1D) subjects (age 13-36 years, duration 10.7 ± 8.4 years, A1c 7.4% ± 0.8% [57 ± 8.7 mmol/mol]) underwent two 105-min exercise studies while under CL control: CL alone and CL+snack. Exercise, commenced at 3 PM, consisted of four 15-min periods of brisk treadmill walking to 65%-70% HRmax (separated by three 5-min rest periods), followed by a 30-min recovery period. Fifteen to 30 g carbohydrate (Gatorade) was provided on snacking visits just before and midway through the exercise period. PG and insulin were measured every 15-20 min during the exercise studies. RESULTS: Baseline PG levels were similar for CL alone (164 ± 16 mg/dL) versus CL+snack (172 ± 11 mg/dL). During exercise, PG levels fell by 53 ± 10 mg/dL without snacking versus a modest 10 ± 13 mg/dL increase in PG with snacking (P = 0.0005); similar differences in the change in PG levels were observed at the end of recovery period. Hypoglycemia requiring rescue treatment (PG ≤60 mg/dL) during exercise occurred in three nonsnacking visits versus none with snacking. During the 75-min exercise period, insulin delivered was 1.8 ± 0.4 U for the CL+snack admission compared to 0.7 ± 0.1 U during CL alone (P = 0.002). CONCLUSION: These results support the use of a simple snacking strategy to avoid exercise-induced lowering of PG while on CL insulin delivery. Persistent insulin infusion during exercise with snacking also appears to be effective in limiting increases in PG at the end of exercise.


Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Exercício Físico , Hipoglicemiantes/administração & dosagem , Insulina/administração & dosagem , Lanches , Adolescente , Adulto , Glicemia , Estudos Cross-Over , Feminino , Humanos , Masculino , Adulto Jovem
8.
Diabetes Care ; 39(7): 1127-34, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27208332

RESUMO

OBJECTIVE: Closed-loop (CL) insulin delivery effectively maintains glucose overnight but struggles when challenged with meals. Use of single-day, 30-µg/meal pramlintide lowers meal excursions during CL. We sought to further elucidate the potential benefits of adjunctive agents after 3-4 weeks of outpatient dose titration. RESEARCH DESIGN AND METHODS: Two CL studies were conducted: one evaluating adjunctive pramlintide and the other liraglutide. Ten subjects (age 16-23 years; A1C 7.2 ± 0.6% [55 ± 6.6 mmol/mol]) completed two 24-h sessions: one on CL alone and one on CL plus 60-µg pramlintide (CL + P), after a 3-4-week outpatient dose escalation. Eleven subjects (age 18-27 years; A1C 7.5 ± 0.9% [58 ± 9.8 mmol/mol]) were studied before and after treatment with 1.8 mg liraglutide (CL + L) after a similar 3-4-week dose escalation period. Timing and content of meals during CL were identical within experiments; meals were not announced. RESULTS: Pramlintide delayed the time to peak plasma glucose (PG) excursion (CL 1.6 ± 0.5 h vs. CL + P 2.6 ± 0.9 h, P < 0.001) with concomitant blunting of peak postprandial increments in PG (P < 0.0001) and reductions in postmeal incremental PG area under the curve (AUC) (P = 0.0002). CL + L also led to reductions in PG excursions (P = 0.05) and incremental PG AUC (P = 0.004), with a 28% reduction in prandial insulin delivery. Outpatient liraglutide therapy led to a weight loss of 3.2 ± 1.8 kg, with a 26% reduction in total daily insulin dose. CONCLUSIONS: Adjunctive pramlintide and liraglutide treatment mitigated postprandial hyperglycemia during CL control; liraglutide demonstrated the additional benefit of weight loss in an insulin-sparing manner. Further investigations of these and other adjunctive agents in long-term outpatient CL studies are needed.


Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Hiperglicemia/prevenção & controle , Hipoglicemiantes/administração & dosagem , Insulina/administração & dosagem , Polipeptídeo Amiloide das Ilhotas Pancreáticas/administração & dosagem , Liraglutida/administração & dosagem , Adolescente , Adulto , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Diabetes Mellitus Tipo 1/sangue , Quimioterapia Combinada , Feminino , Humanos , Hiperglicemia/tratamento farmacológico , Hipoglicemiantes/efeitos adversos , Insulina/efeitos adversos , Sistemas de Infusão de Insulina , Polipeptídeo Amiloide das Ilhotas Pancreáticas/efeitos adversos , Liraglutida/efeitos adversos , Masculino , Refeições/fisiologia , Período Pós-Prandial/efeitos dos fármacos , Adulto Jovem
9.
Diabetes Care ; 37(3): 773-9, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24170766

RESUMO

OBJECTIVE: An integrated sensor-augmented pump system has been introduced that interrupts basal insulin infusion for 2 h if patients fail to respond to low-glucose alarms. It has been suggested that such interruptions of basal insulin due to falsely low glucose levels detected by sensor could lead to diabetic ketoacidosis. We hypothesized that random suspension of basal insulin for 2 h in the overnight period would not lead to clinically important increases in blood ß-hydroxybutyrate levels despite widely varying glucose values prior to the suspension. RESEARCH DESIGN AND METHODS: Subjects measured blood glucose and blood ß-hydroxybutyrate levels using a meter each night at 9:00 p.m., then fasted until the next morning. On control nights, the usual basal rates were continued; on experimental nights, the basal insulin infusion was reprogrammed for a 2-h zero basal rate at random times after 11:30 p.m. RESULTS: In 17 type 1 diabetic subjects (mean age 24 ± 9 years, diabetes duration 14 ± 11 years, A1C level 7.3 ± 0.5% [56 mmol/mol]), blood glucose and blood ß-hydroxybutyrate levels were similar at 9:00 p.m. on suspend nights (144 ± 63 mg/dL and 0.09 ± 0.07 mmol/L) and nonsuspend nights (151 ± 65 mg/dL and 0.08 ± 0.06 mmol/L) (P = 0.39 and P = 0.47, respectively). Fasting morning blood glucose levels increased after suspend nights compared with nonsuspend nights (191 ± 68 vs. 141 ± 75 mg/dL, P < 0.0001), and the frequency of fasting hypoglycemia decreased the morning following suspend nights (P < 0.0001). Morning blood ß-hydroxybutyrate levels were slightly higher after suspension (0.13 ± 0.14 vs. 0.09 ± 0.11 mmol/L, P = 0.053), but the difference was not clinically important. CONCLUSIONS: Systems that suspend basal insulin for 2 h are safe and do not lead to clinically significant ketonemia even if the blood glucose level is elevated at the time of the suspension.


Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Insulina/administração & dosagem , Ácido 3-Hidroxibutírico/metabolismo , Adolescente , Adulto , Glicemia/metabolismo , Diabetes Mellitus Tipo 1/sangue , Cetoacidose Diabética/sangue , Cetoacidose Diabética/tratamento farmacológico , Esquema de Medicação , Feminino , Humanos , Hipoglicemia/sangue , Hipoglicemia/tratamento farmacológico , Sistemas de Infusão de Insulina , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Adulto Jovem
10.
Diabetes Technol Ther ; 16(1): 20-5, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24367934

RESUMO

OBJECTIVE: This study was undertaken to investigate the effect of an insulin infusion site warming device, the InsuPatch(40)(™) (IP(40)) (InsuLine Medical Ltd., Petach-Tikvah, Israel), on insulin aspart pharmacodynamics (PD) and pharmacokinetics (PK) in adolescents with type 1 diabetes. SUBJECTS AND METHODS: Seventeen subjects with type 1 diabetes (age, 15±1 years; hemoglobin A1c, 7.5±0.2% [58±2.2 mmol/mol]) underwent two euglycemic clamps performed on separate mornings with and without IP(40) activation with warming temperature at 40°C. On both days, the basal infusion was suspended, and glucose levels were maintained between 90 and 100 mg/dL by a variable rate dextrose infusion for up to 5 h after a 0.2 U/kg bolus of insulin aspart. RESULTS: Time to peak insulin action and time to half-maximal action occurred earlier with a greater early glucodynamic effect (area under the curve [AUC] for glucose infusion rate from 0 to 30 min) with IP(40) than without the IP(40), whereas the AUC for the time-action profile and the peak action did not differ with and without infusion site warming. PK parameters were in agreement with PD parameters, namely, a significantly earlier time to reach the maximum increment in insulin concentrations and greater early bioavailability (AUC for the change in insulin concentration from 0 to 30 min) with the IP(40). The tail of the plasma insulin response curve was also shortened with infusion site warming, with the time to reach baseline insulin concentration occurring significantly earlier (P=0.04). CONCLUSIONS: Our data demonstrate that skin warming around the infusion site to 40°C with the IP(40) is an effective means to accelerate absorption and action of rapid-acting insulin. These improvements in time-action responses have the potential to enhance the performance of open- and closed-loop insulin delivery systems.


Assuntos
Glicemia/metabolismo , Diabetes Mellitus Tipo 1/sangue , Hemoglobina A Glicada/metabolismo , Temperatura Alta , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/farmacocinética , Insulina Aspart/administração & dosagem , Insulina Aspart/farmacocinética , Absorção , Adolescente , Área Sob a Curva , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/metabolismo , Feminino , Técnica Clamp de Glucose , Humanos , Hipoglicemiantes/metabolismo , Insulina Aspart/metabolismo , Sistemas de Infusão de Insulina , Masculino , Fluxo Sanguíneo Regional , Temperatura Cutânea , Fatores de Tempo , Resultado do Tratamento
11.
Diabetes Care ; 36(10): 2909-14, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23757427

RESUMO

OBJECTIVE: Afternoon exercise increases the risk of nocturnal hypoglycemia (NH) in subjects with type 1 diabetes. We hypothesized that automated feedback-controlled closed-loop (CL) insulin delivery would be superior to open-loop (OL) control in preventing NH and maintaining a higher proportion of blood glucose levels within the target blood glucose range on nights with and without antecedent afternoon exercise. RESEARCH DESIGN AND METHODS: Subjects completed two 48-h inpatient study periods in random order: usual OL control and CL control using a proportional-integrative-derivative plus insulin feedback algorithm. Each admission included a sedentary day and an exercise day, with a standardized protocol of 60 min of brisk treadmill walking to 65-70% maximum heart rate at 3:00 p.m. RESULTS: Among 12 subjects (age 12-26 years, A1C 7.4±0.6%), antecedent exercise increased the frequency of NH (reference blood glucose<60 mg/dL) during OL control from six to eight events. In contrast, there was only one NH event each on nights with and without antecedent exercise during CL control (P=0.04 vs. OL nights). Overnight, the percentage of glucose values in target range was increased with CL control (P<0.0001). Insulin delivery was lower between 10:00 p.m. and 2:00 a.m. on nights after exercise on CL versus OL, P=0.008. CONCLUSIONS: CL insulin delivery provides an effective means to reduce the risk of NH while increasing the percentage of time spent in target range, regardless of activity level in the mid-afternoon. These data suggest that CL control could be of benefit to patients with type 1 diabetes even if it is limited to the overnight period.


Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Exercício Físico/fisiologia , Hipoglicemia/tratamento farmacológico , Insulina/administração & dosagem , Insulina/uso terapêutico , Adolescente , Adulto , Glicemia/efeitos dos fármacos , Criança , Diabetes Mellitus Tipo 1/sangue , Feminino , Humanos , Masculino , Fatores de Tempo , Adulto Jovem
12.
Pediatr Diabetes ; 14(3): 168-73, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23107353

RESUMO

BACKGROUND AND OBJECTIVE: Subcutaneously injected rapid-acting insulin analogs do not replicate physiologic insulin action due to delays in their onset and peak action resulting in postprandial glucose excursions. The InsuPatch (IP) is a novel insulin infusion site warming device developed to accelerate insulin action by increasing blood flow to the area of insulin absorption. Thirteen adolescents with type 1 diabetes (T1D, mean age 14 ± 4 yr) were enrolled in this study to investigate the effect of the IP on the pharmacodynamics and pharmacokinetics of a 0.2 unit/kg bolus dose of aspart insulin using the euglycemic clamp technique. RESEARCH DESIGN AND METHODS: Each subject underwent two euglycemic clamp procedures on separate occasions: one with IP and one without IP activation in random order. RESULTS: When the insulin bolus was given with IP activation as compared to without IP activation, time to reach maximum insulin action (T(GIRmax)) and to reach 50% maximum action (T(50%GIRmax)) were 35 and 18 min earlier (125 ± 8 min vs. 90 ± 6 min, p = 0.002 and 58 ± 5 min. vs. 40 ± 3 min, p = 0.01, respectively), and the area under curve, AUC(GIR 0-90 min), reflecting early glucodynamic action, was significantly greater (p = 0.001). IP activation also accelerated the rise in plasma insulin levels after the bolus (p = 0.03) and resulted in a higher peak (p = 0.04) and greater overall increase (p = 0.02) in plasma insulin levels. CONCLUSIONS: Our results show that insulin infusion site warming with IP activation accelerates the time action profile of aspart insulin which may be of benefit to current open-loop and future closed-loop insulin delivery in patients with T1D.


Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Insulina Aspart/administração & dosagem , Sistemas de Infusão de Insulina , Fluxo Sanguíneo Regional , Absorção , Adolescente , Glicemia/análise , Criança , Estudos Cross-Over , Diabetes Mellitus Tipo 1/sangue , Feminino , Técnica Clamp de Glucose , Temperatura Alta , Humanos , Hipoglicemiantes/sangue , Hipoglicemiantes/farmacocinética , Hipoglicemiantes/uso terapêutico , Infusões Subcutâneas , Insulina Aspart/sangue , Insulina Aspart/farmacocinética , Insulina Aspart/uso terapêutico , Masculino , Temperatura Cutânea
13.
J Diabetes Sci Technol ; 6(5): 1123-30, 2012 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-23063039

RESUMO

BACKGROUND: Closed-loop (CL) insulin delivery systems utilizing proportional-integral-derivative (PID) controllers have demonstrated susceptibility to late postprandial hypoglycemia because of delays between insulin delivery and blood glucose (BG) response. An insulin feedback (IFB) modification to the PID algorithm has been introduced to mitigate this risk. We examined the effect of IFB on CL BG control. METHODS: Using the Medtronic ePID CL system, four subjects were studied for 24 h on PID control and 24 h during a separate admission with the IFB modification (PID + IFB). Target glucose was 120 mg/dl; meals were served at 8:00 AM, 1:00 PM, and 6:00 PM and were identical for both admissions. No premeal manual boluses were given. Reference BG excursions, defined as incremental glucose rise from premeal to peak, and postprandial BG area under the curve (AUC; 0-5 h) were compared. Results are reported as mean ± standard deviation. RESULTS: The PID + IFB control resulted in higher mean BG levels compared with PID alone (153 ± 54 versus 133 ± 56 mg/dl; p < .0001). Postmeal BG excursions (114 ± 28 versus 114 ± 47 mg/dl) and AUCs (285 ± 102 versus 255 ± 129 mg/dl/h) were similar under both conditions. Total insulin delivery averaged 57 ± 20 U with PID versus 45 ± 13 U with PID + IFB (p = .18). Notably, eight hypoglycemic events (BG < 60 mg/dl) occurred during PID control versus none during PID + IFB. CONCLUSIONS: Addition of IFB to the PID controller markedly reduced the occurrence of hypoglycemia without increasing meal-related glucose excursions. Higher average BG levels may be attributable to differences in the determination of system gain (Kp) in this study. The prevention of postprandial hypoglycemia suggests that the PID + IFB algorithm may allow for lower target glucose selection and improved overall glycemic control.


Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Retroalimentação Fisiológica/efeitos dos fármacos , Sistemas de Infusão de Insulina , Insulina/administração & dosagem , Insulina/farmacologia , Administração Metronômica , Adolescente , Adulto , Algoritmos , Glicemia/análise , Glicemia/efeitos dos fármacos , Automonitorização da Glicemia/instrumentação , Estudos Cross-Over , Diabetes Mellitus Tipo 1/sangue , Feminino , Humanos , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/farmacologia , Masculino , Adulto Jovem
14.
Diabetes Care ; 35(10): 1994-9, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22815298

RESUMO

OBJECTIVE: Even under closed-loop (CL) conditions, meal-related blood glucose (BG) excursions frequently exceed target levels as a result of delays in absorption of insulin from the subcutaneous site of infusion. We hypothesized that delaying gastric emptying with preprandial injections of pramlintide would improve postprandial glycemia by allowing a better match between carbohydrate and insulin absorptions. RESEARCH DESIGN AND METHODS: Eight subjects (4 female; age, 15-28 years; A1C, 7.5 ± 0.7%) were studied for 48 h on a CL insulin-delivery system with a proportional integral derivative algorithm with insulin feedback: 24 h on CL control alone (CL) and 24 h on CL control plus 30-µg premeal injections of pramlintide (CLP). Target glucose was set at 120 mg/dL; timing and contents of meals were identical on both study days. No premeal manual boluses were given. Differences in reference BG excursions, defined as the incremental glucose rise from premeal to peak, were compared between conditions for each meal. RESULTS: CLP was associated with overall delayed time to peak BG (2.5 ± 0.9 vs. 1.5 ± 0.5 h; P < 0.0001) and reduced magnitude of glycemic excursion (88 ± 42 vs. 113 ± 32 mg/dL; P = 0.006) compared with CL alone. Pramlintide effects on glycemic excursions were particularly evident at lunch and dinner, in association with higher premeal insulin concentrations at those mealtimes. CONCLUSIONS: Pramlintide delayed the time to peak postprandial BG and reduced the magnitude of prandial BG excursions. Beneficial effects of pramlintide on CL may in part be related to higher premeal insulin levels at lunch and dinner compared with breakfast.


Assuntos
Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 1/sangue , Hipoglicemiantes/uso terapêutico , Polipeptídeo Amiloide das Ilhotas Pancreáticas/uso terapêutico , Adolescente , Adulto , Diabetes Mellitus Tipo 1/tratamento farmacológico , Feminino , Humanos , Insulina/sangue , Masculino , Refeições , Pâncreas Artificial , Período Pós-Prandial
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