RESUMEN
AIM: We evaluated the effects of an alpha-glucosidase inhibitor, acarbose, on glucose homoeostasis during postprandial exercise in Type 1 diabetic subjects. METHODS: Seven Type 1 diabetic subjects with good glycaemic control on ultralente-regular insulin were randomized in a single blind cross-over study to acarbose 100 mg or placebo taken with a mixed meal (600 kcal, 75 g carbohydrates), followed 90 min later by 30 min of exercise at 50% maximum aerobic capacity. Glucose turnover was measured by tracer (d-[6,6,2H2]glucose) methodology, and intestinal glucose absorption was quantified using carbohydrate polymers labelled with [13C]glucose. RESULTS: Acarbose resulted in a significant decrease in the postprandial glycaemic rise (mean +/- SEM 2.9 +/- 0.6 vs. 5.0 +/- 0.7 mmol/l; P < 0.005) and in the glycaemic nadir during exercise (- 0.8 +/- 0.6 vs. 0.9 +/- 1.3 mmol/l below baseline; P < 0.05). Total glucose appearance increased similarly under the two treatments during the postprandial (27.0 vs. 27.9 micromol per kg per min) and exercise (33.9 vs. 33.5 micromol per kg per min) periods. Mean glucose absorption was significantly delayed by acarbose (7.8 vs. 10.2 micromol per kg per min; P < 0.02), but was compensated by the lack of postprandial suppression of hepatic glucose production (106% of basal hepatic glucose production vs. 81%; P < 0.006). Episodes of hypoglycaemia were no different (three vs. six). CONCLUSION: These results indicate that, in Type 1 diabetic subjects, acarbose results in a better glycaemic profile during postprandial exercise and suggest that it could lead to a lower risk of exercise-induced hypoglycaemia due to delayed glucose absorption and less suppression of hepatic glucose production.
Asunto(s)
Glucemia/metabolismo , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Inhibidores Enzimáticos/uso terapéutico , Ejercicio Físico/fisiología , Alimentos , Inhibidores de Glicósido Hidrolasas , Acarbosa/uso terapéutico , Adulto , Estudios Cruzados , Glucosa/biosíntesis , Homeostasis , Humanos , Cinética , Hígado/metabolismo , Masculino , PlacebosRESUMEN
OBJECTIVE: To evaluate and validate appropriate premeal insulin dose reductions for postprandial exercises of different intensities and durations to minimize the risk of exercise-induced hypoglycemia in type 1 diabetic subjects. RESEARCH DESIGN AND METHODS: Eight male type 1 diabetic patients on a basal-bolus insulin regimen of ultralente (UL) as basal insulin and lispro (LP) as premeal insulin were tested in a randomized, crossover fashion during postprandial exercise at 25% VO2max for 60 min, 50% VO2max for 30 and 60 min, and 75% VOmax for 30 min starting 90 min after a standardized mixed breakfast (600 kcal, 75 g carbohydrates). Each subject served as his own control and was rested after a full dose of insulin LP (LP 100%) and/or 50% (LP 50%) and/or 25% (LP 25%) of the current dose. RESULTS: At all intensities, the full premeal insulin dose was associated with an increased risk of hypoglycemia. At 25% VO2max for 60 min, a 50% reduction in the premeal insulin dose resulted in plasma glucose of -0.62 mmol/l compared with baseline at the end of exercise. At 50% VO2max for 30 and 60 min, 50 and 75% reductions of the premeal insulin dose were associated with plasma glucose of -0.39 and +0.49 mmol/l, respectively, at the end of the exercise. At 75% VO2max, a 75% reduction of the premeal insulin dose was required to achieve appropriate postexercise plasma glucose (+0.71 mmol/l). Such reductions in the premeal insulin dose resulted in a 75% decrease in the incidence of exercise-induced hypoglycemia. CONCLUSIONS In well-controlled type 1 diabetic subjects on intensive insulin therapy with the basal-bolus (UL-LP) insulin regimen, risk of hypoglycemia can be minimized during postprandial exercises of different intensities and different durations by appropriate reduction of premeal insulin LP.
Asunto(s)
Diabetes Mellitus Tipo 1/tratamiento farmacológico , Ejercicio Físico , Hipoglucemiantes/uso terapéutico , Insulina de Acción Prolongada/uso terapéutico , Insulina/uso terapéutico , Adulto , Glucemia/metabolismo , Estudios Cruzados , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 1/fisiopatología , Esquema de Medicación , Ingestión de Alimentos , Ingestión de Energía , Guías como Asunto , Humanos , Hipoglucemia/epidemiología , Hipoglucemia/prevención & control , Hipoglucemiantes/administración & dosificación , Insulina/administración & dosificación , Insulina/análogos & derivados , Insulina Lispro , Insulina de Acción Prolongada/administración & dosificación , Masculino , Consumo de Oxígeno , Periodo Posprandial , Factores de Riesgo , Factores de TiempoRESUMEN
To evaluate the influence of a low glycaemic index (GI), high GI and high fibre diet on glycaemic control and insulin requirement in Type 1 diabetic patients on intensive insulin therapy, nine well-controlled, highly-motivated Type 1 diabetic patients were put on a control diet for 12 days and then randomized in a consecutive manner to 12 days of each diet, in a crossover design. During each experimental diet, the study subjects adjusted their premeal insulin (soluble) dose to maintain their 1-h postprandial capillary glucose at or below 10 mmol l(-1). At the end of each experimental diet, they were submitted to a standardized breakfast of the diet under study, using the same premeal insulin dose as that required for the control diet. The control diet contained 16.0+/-3.0 g of fibre day(-1) with a GI of 77.4+/-2.7 compared to 15.3+/-6.3 and 66.2+/-1.2 for the low GI diet, 17.1+/-7.2 and 92.9+/-3.6 for the high GI diet, and 56.1+/-3.6 (including 15 g of guar) and 73.5+/-2.1 for the high fibre diet. Prebreakfast capillary blood glucose (6.2+/-1.2 mmol l(-1)) on the low GI diet and postbreakfast capillary blood glucose (8.7+/-1.8 mmol l(-1)) on the high fibre diet were significantly lower than the values obtained with the control diet (8.0+/-1.8 and 10.6+/-2.4, respectively; p<0.05). No change in premeal or basal insulin dose was required. During the standardized breakfasts, the incremental area under the curve was 1.6+/-1.5 mmol l(-1) min(-1) for the control diet compared to 1.1+/-1.8 for the low GI diet, 3.2+/-1.4 for the high GI diet (p<0.05 versus low GI and high fibre; p=0.08 versus control), and 1.0+/-0.9 for the high fibre diet. These observations indicate that in well-controlled Type 1 diabetic subjects on intensive insulin therapy, major alterations in the GI and fibre content of meals induce small but significant changes in glucose profile. In everyday life, however, these differences are blunted, and plasma glucose remains within the target range for optimal metabolic control.
Asunto(s)
Glucemia/metabolismo , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Dieta para Diabéticos , Carbohidratos de la Dieta , Fibras de la Dieta , Glucosa/metabolismo , Hipoglucemiantes/uso terapéutico , Insulina/uso terapéutico , Estudios Cruzados , Diabetes Mellitus Tipo 1/dietoterapia , Esquema de Medicación , Femenino , Fructosamina/sangre , Hemoglobina Glucada/análisis , Humanos , Hipoglucemiantes/administración & dosificación , Insulina/administración & dosificación , Sistemas de Infusión de Insulina , MasculinoRESUMEN
This study was designed to characterize the impact of endurance training on the hepatic response to glucagon. We measured the effect of glucagon on hepatic glucose production (HGP) in resting trained (n = 8) and untrained (n = 8) healthy male subjects (maximal rate of O2 consumption: 65.9 +/- 1.6 vs. 46.8 +/- 0.6 ml O2.kg-1.min-1, respectively, P < 0.001). Endogenous insulin and glucagon were suppressed by somatostatin (somatotropin release-inhibiting hormone) infusion (450 micrograms/h) over 4 h. Insulin (0.15 mU.kg-1.min-1) was infused throughout the study, and glucagon (1.5 ng.kg-1.min-1) was infused over the last 2 h. During the latter period, plasma glucagon and insulin remained constant at 138.2 +/- 3.1 vs. 145.3 +/- 2.1 ng/l and at 95.5 +/- 4.5 vs. 96.2 +/- 1.9 pmol/l in trained and untrained subjects, respectively. Plasma glucose increased and peaked at 11.4 +/- 1.1 mmol/l in trained subjects and at 8.9 +/- 0.8 mmol/l in untrained subjects (P < 0.001). During glucagon stimulation, the mean increase in HGP area under the curve was 15.8 +/- 2.8 mol.kg-1.min-1 in trained subjects compared with 7.4 +/- 1.6 mol.kg-1.min-1 in untrained subjects (P < 0.01) over the first hour and declined to 6.8 +/- 2.8 and 4.9 +/- 1.4 mol.kg-1.min-1 during the second hour. In conclusion, these observations indicate that endurance training is associated with an increase in HGP in response to physiological levels of glucagon, thus suggesting an increase in hepatic glucagon sensitivity.
Asunto(s)
Glucagón/farmacología , Gluconeogénesis/efectos de los fármacos , Hígado/metabolismo , Resistencia Física/fisiología , Adulto , Alanina/sangre , Glucagón/antagonistas & inhibidores , Glucagón/sangre , Humanos , Infusiones Intravenosas , Insulina/administración & dosificación , Insulina/sangre , Insulina/farmacología , Antagonistas de Insulina/farmacología , Lactatos/sangre , Hígado/efectos de los fármacos , Masculino , Consumo de Oxígeno/efectos de los fármacos , Valores de Referencia , Somatostatina/administración & dosificación , Somatostatina/farmacología , Factores de TiempoRESUMEN
OBJECTIVE: To characterize the effect of pregnancy on glucose turnover and gluconeogenesis in healthy women and in women with well-controlled insulin-dependent diabetes mellitus (IDDM). DESIGN: Prospective clinical study. SETTING: Clinical research unit of the Hôtel-Dieu de Montréal hospital. PARTICIPANTS: Five healthy pregnant women and 6 pregnant women with IDDM. INTERVENTIONS: Glucose turnover and gluconeogenesis in the postabsorptive state at 16 and 32 weeks' gestation and at 24 weeks postpartum were studied with the use of a double stable isotope technique (D[2,3,4,6,6(2)H]-glucose and L[1,2,3(13)C]-alanine). In the women with IDDM, plasma glucose levels were controlled by continuous subcutaneous insulin infusion throughout pregnancy and with a Biostator on the morning of the study. RESULTS: In the women without IDDM, hepatic glucose production was 11.6 (standard error of the mean [SEM] 2.2) mumol/kg per minute at 16 weeks' gestation, 12.5 (SEM 1.8) mumol/kg per minute at 32 weeks' gestation, and 13.2 (SEM 1.9) mumol/kg per minute at 24 weeks postpartum. In the women with IDDM, it was 10.7 (SEM 2.4) mumol/kg per minute, 10.5 (SEM 1.2) mumol/kg per minute and 12.3 (SEM 0.5) mumol/kg per minute at the same respective periods. The difference in levels between the 2 groups was not significant. Levels of the gluconeogenic precursors alanine and lactate were increased during pregnancy in both the women without IDDM (from 0.18 [SEM 0.02] mmol/L and 0.64 [SEM 0.09] mmol/L, respectively, to 0.25 [SEM 0.02] mmol/L and 1.15 [SEM 0.17] mmol/L, respectively, p < 0.01) and in those with IDDM (from 0.15 [SEM 0.01] mmol/L and 0.47 [SEM 0.04] mmol/L, respectively, to 0.19 [SEM 0.02] mmol/L and 0.70 [SEM 0.01] mmol/L, respectively, p < 0.05). After an overnight fast, gluconeogenesis from alanine was not affected by pregnancy in both groups of women. In the women without IDDM, the plasma insulin level was low in early pregnancy (33.6 [SEM 3.6] pmol/L) and increased in late gestation (87.6 [SEM 9.6] pmol/L) compared with postpartum levels (60.0 [SEM 7.8] pmol/L). Plasma glucagon levels tended to rise in late gestation (from 95.1 [SEM 6.7] ng/L to 116.0 [SEM 36.0] ng/L). In the women with IDDM, the free plasma insulin and plasma glucagon levels were higher in early pregnancy (55.2 [SEM 6.6] pmol/L and 196.1 [SEM 29.8] ng/L, respectively) and did not change significantly during pregnancy. CONCLUSION: Basal glucose turnover and gluconeogenesis are not increased during pregnancy in women without IDDM or in women with well-controlled IDDM. The decrease in the plasma glucose level during pregnancy suggests that the use of glucose by the growing fetus is augmented and that this is not totally compensated for by a rise in postabsorptive hepatic glucose production. The glucose requirement by the growing fetus is probably supplied by the increased postprandial plasma glucose level.
Asunto(s)
Diabetes Mellitus Tipo 1/metabolismo , Gluconeogénesis , Glucosa/metabolismo , Embarazo en Diabéticas/metabolismo , Alanina/metabolismo , Isótopos de Carbono , Deuterio , Estradiol/sangre , Ayuno , Femenino , Glucagón/sangre , Humanos , Hidrocortisona/sangre , Insulina/sangre , Hígado/metabolismo , Lactógeno Placentario/sangre , Embarazo , Progesterona/sangre , Prolactina/sangre , Estudios ProspectivosRESUMEN
OBJECTIVE: To study the effect of fluoxetine, a specific serotonin reuptake inhibitor, on insulin sensitivity in obese patients with non-insulin-dependent diabetes mellitus (NIDDM) independently of its action on body weight. RESEARCH DESIGN AND METHODS: In a randomized, double-blind, placebo-controlled trial, insulin-mediated glucose disposal was measured in 12 obese patients with NIDDM on diet alone before and after four weeks of treatment with either placebo (n = 6) or fluoxetine (n = 6) at a dose level of 60 mg once a day. Insulin-mediated glucose disposal was assessed by the 2-step euglycemic hyperinsulinemic clamp technique. Patients were instructed on a weight-maintaining diet. RESULTS: Insulin infusion at 40 mU.m-2.min-1 resulted in insulin levels of 720 +/- 70 pmol. L-1 with a mean plasma glucose value of 6.4 +/- 0.2 mmol. L-1. Compared to placebo, fluoxetine increased glucose disposal (M) by 2.4-fold (P < 0.05), the insulin sensitivity index (M/I) by 2.7-fold (P < 0.03) and the glucose metabolic clearance rate (MCR) by 2.9-fold (P < 0.03). Insulin infusion at 400 mU.m-2. min-1 elicited insulin levels of 12947 +/- 1512 pmol. L-1 with a mean plasma glucose value of 5.6 +/- 0.4 mmol. L-1. Compared to placebo, fluoxetine increased M by 30% (P = NS), M/I by 40% (P < 0.04) and MCR by 23% (P < 0.04). Patient weight remained stable throughout the study with no change in dietary intake. CONCLUSION: Fluoxetine improves insulin-mediated glucose disposal in obese patients with NIDDM independently of weight loss.
Asunto(s)
Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus/tratamiento farmacológico , Fluoxetina/uso terapéutico , Insulina/sangre , Obesidad , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéutico , Glucemia/efectos de los fármacos , Glucemia/metabolismo , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/fisiopatología , Método Doble Ciego , Femenino , Fluoxetina/administración & dosificación , Técnica de Clampeo de la Glucosa , Humanos , Infusiones Intravenosas , Insulina/administración & dosificación , Insulina/metabolismo , Masculino , Persona de Mediana Edad , Inhibidores Selectivos de la Recaptación de Serotonina/administración & dosificación , Pérdida de Peso/efectos de los fármacosRESUMEN
This study was designed to further characterize the role of insulin and glucagon in the regulation of glucose production and gluconeogenesis during a 2-h mild intensity exercise (40% VO2max) in 14 h fasted healthy male subjects. Endogenous insulin and glucagon secretions were suppressed by the infusion of somatostatin. The pancreatic hormones were replaced singly or in combination to match the hormonal concentrations observed during exercise in control subjects. Glucose turnover was determined by a tracer method using the stable isotope D-[2,3,4,6,6-2H]glucose. Gluconeogenesis was estimated by the simultaneous infusion of L-[1,2,3-13C]alanine to follow the conversion of alanine to glucose. Hepatic glucose production significantly increased from a resting rate of 12.1 +/- 0.2 to 27.6 +/- 1.4 mumol.kg-1.min-1 during exercise (p < 0.05). In the absence of glucagon, this increase in hepatic glucose production during exercise was totally abolished (p < 0.05). When insulin was made deficient, in the presence of glucagon, there was an overshoot in the increase in hepatic glucose production during exercise to 36.4 +/- 1.6 mumol.kg-1.min-1 (p < 0.05). The normal increase in hepatic glucose output during exercise was reproduced when both insulin and glucagon were replaced. Exercise increased gluconeogenesis by 47% above the resting level (p < 0.05). When glucagon was made deficient, in the absence or presence of insulin, this increase in gluconeogenesis was totally suppressed (p < 0.05). Furthermore, glucagon replacement during exercise in the absence of insulin resulted in a further increase in gluconeogenesis to 93% above resting value (p < 0.05). From these observations, it is concluded that during prolonged mild intensity exercise in healthy subjects, the rise in glucagon is essential for the increase in hepatic glucose production and the increase in gluconeogenesis. It is also suggested that the lower level of insulin during exercise still exerts a restraining effect on glucagon-stimulated glucose production and gluconeogenesis, thus preventing hyperglycemia.
Asunto(s)
Ejercicio Físico/fisiología , Glucagón/fisiología , Gluconeogénesis/fisiología , Glucosa/metabolismo , Insulina/fisiología , Hígado/metabolismo , Adulto , Alanina/sangre , Alanina/metabolismo , Glucemia/metabolismo , Isótopos de Carbono , Deuterio , Ayuno/metabolismo , Glucagón/metabolismo , Glicerol/sangre , Humanos , Insulina/sangre , Insulina/metabolismo , Secreción de Insulina , Ácido Láctico/sangre , Masculino , Hormonas Pancreáticas/sangre , Somatostatina/farmacologíaRESUMEN
The present study was designed to characterize further the role of insulin in the regulation of glucose utilization during a 2-h exercise at 40% VO2max in 14 h fasted, healthy subjects. Endogenous insulin and glucagon were suppressed by somatostatin infusion and replaced singly or in combination to match the hormonal concentrations observed during similar exercise in saline-treated control subjects. Glucose kinetics were determined by a tracer method using D-[2,3,4,6,6-2H]glucose. In the exercising controls, during the last hour of the exercise, plasma glucose remained stable (4.26 +/- 0.06 mmol/L) and glucose utilization (Rd) increased significantly (p < 0.05) from 12.2 +/- 0.2 to 28.6 +/- 1.3 mumol.kg-1.min-1. During insulin deficiency without glucagon replacement, plasma glucose was maintained at 3.74 +/- 0.10 mmol/L by dextrose infusion, but with glucagon replacement plasma glucose increased to 6.69 +/- 0.24 mmol/L (p < 0.05). These hormonal changes were associated with an increase in Rd to 18.6 +/- 1.1 mumol.kg-1.min-1 (p = ns versus resting controls) and to 37.9 +/- 1.9 mumol.kg-1.min-1 (p < 0.05 versus resting controls), respectively. When insulin was replaced without glucagon replacement, plasma glucose was maintained at 3.85 +/- 0.06 mmol/L by dextrose infusion and Rd increased significantly (p < 0.05) from the resting value to 25.9 +/- 0.7 mumol.kg-1.min-1. When insulin was replaced together with glucagon, the plasma glucose (4.29 +/- 0.15 mmol/L) and the Rd (32.1 +/- 0.9 mumol.kg-1.min-1, p < 0.05 versus the resting value) obtained were similar to the values from the saline exercising control. Glucose metabolic clearance rate (MCR) significantly increased (p < 0.05) during exercise in all protocols. When insulin was made deficient, MCR increased 2-fold (p < 0.05) during exercise (2.7 to 4.8 and 5.4 mL.kg-1.min-1, respectively, with and without glucagon deficiency). However, when insulin was present, with and without glucagon deficiency, it increased further to 6.7 and 7.5 mL.kg-1.min-1, respectively, and values were different (p < 0.05) from glucose MCRs during insulin deficiencies. It is concluded that in 14 h fasted, healthy subjects, exercise per se can stimulate whole body glucose uptake even when insulin is made deficient. Insulin is necessary, however, for optimal glucose utilization during prolonged mild intensity exercise.
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Ejercicio Físico/fisiología , Glucosa/metabolismo , Insulina/fisiología , Adulto , Glucemia/efectos de los fármacos , Glucemia/metabolismo , Ayuno/metabolismo , Ácidos Grasos no Esterificados/sangre , Glucagón/sangre , Humanos , Insulina/sangre , Masculino , Hormonas Pancreáticas/sangre , Hormonas Pancreáticas/metabolismo , Somatostatina/farmacologíaAsunto(s)
Actividades Cotidianas , Demencia/rehabilitación , Terapia del Lenguaje , Terapia Ocupacional , Anciano , HumanosRESUMEN
The present study was designed to compare continuous subcutaneous insulin infusion (CSII) using the Mill-Hill Infuser (Muirhead Medical Products Ltd., London, England) with multiple injections (MI) using the Medi-Jector (Derata Corporation, Minneapolis, Minnesota) in the treatment of insulin-dependent diabetes mellitus (IDDM), and to assess the effect of glucose control on diabetes complications. Twelve diabetic subjects were treated 3 mo with CSII and 3 mo with MI (bedtime ultralente and premeal boluses of regular insulin) in a randomized fashion. Prestudy preprandial/postprandial glucose levels were 147-215 mg/dl and improved to 108-138 mg/dl during CSII, and to 115-139 mg/dl during MI with glycosylated hemoglobin of 12.9%, 9.1%, and 8.7%, respectively. This improved glucose control with either CSII or MI was associated with an increase in sural nerve conductivity from 42.9 to 45 m/s and a decrease in proteinuria from 1.9 to 0.5 g/24 h. The 24-h insulin dose consisted of 45 U before the study, 44 U during CSII, and 56 U during MI. After the study, seven patients opted to continue with the Mill-Hill Infuser, and five with the Medi-Jector. We conclude the following: (1) treatment with both the Mill-Hill Infuser and the Medi-Jector was well accepted by the patients and resulted in similar improvement in measured blood glucose and glycosylated hemoglobin; (2) this improved metabolic control was associated with an increased nerve conductivity and a decreased protein excretion; and (3) MI required 20% more insulin than CSII to achieve similar glycemic control.