RESUMEN
We evaluated the effect of sitagliptin on glycemic control, endogenous insulin secretion, and beta cell function in Japanese patients with type 2 diabetes mellitus (T2DM) receiving a combination of oral antidiabetics and basal insulin analog glargine (basal-supported oral therapy [BOT]). Twenty-one patients showing inadequate glycemic control with BOT were given dipeptidylpeptidase-4 inhibitor (DPP-4I) sitagliptin at 50 mg/day for 12 weeks. Clinical markers of glycemic control, HbA1c, glycated albumin (GA), and 1,5-anhydroglucitol (1,5-AG), were measured before and 4 and 12 weeks after the start of sitagliptin. A 2-hour morning meal test was performed upon enrollment and at 12 weeks, and plasma glucose (PG), serum C-peptide, and plasma intact proinsulin (PI) were measured. HbA1c, GA, and 1,5-AG at 4 and 12 weeks were significantly improved over enrollment levels. The area under the PG concentration curve (AUC-PG) during the meal test at 12 weeks was significantly reduced (from 350 ± 17 mg ï½¥ hr/dL before sitagliptin treatment to 338 ± 21 mg ï½¥ hr/dL [mean ± SE], P < 0.05,); the AUC-C-peptide was unchanged (from 3.4 ± 0.4 ng ï½¥ hr/mL to 3.6 ± 0.5 ng ï½¥ hr/mL). However, both fasting and 2-hour PI/C-peptide ratios at 12 weeks were significantly decreased (from 13.3 ± 2.3 to 11.1 ± 2.0 [P < 0 .05] and from 9.5 ± 1.6 to 5.3 ± 0.9 [P < 0.01], respectively). Adding sitagliptin to BOT in Japanese T2DM patients appears to improve glycemic control without increasing endogenous insulin secretion and to reduce fasting and 2-hour postprandial PI/C-peptide ratios.
Asunto(s)
Diabetes Mellitus Tipo 2/tratamiento farmacológico , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , Resistencia a Medicamentos , Hiperglucemia/prevención & control , Células Secretoras de Insulina/efectos de los fármacos , Proinsulina/metabolismo , Pirazinas/uso terapéutico , Triazoles/uso terapéutico , Administración Oral , Anciano , Algoritmos , Biomarcadores/sangre , Péptido C/sangre , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/etnología , Diabetes Mellitus Tipo 2/fisiopatología , Inhibidores de la Dipeptidil-Peptidasa IV/administración & dosificación , Monitoreo de Drogas , Quimioterapia Combinada , Ácidos Grasos no Esterificados/antagonistas & inhibidores , Ácidos Grasos no Esterificados/sangre , Femenino , Hemoglobina Glucada/análisis , Humanos , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/uso terapéutico , Insulina Glargina , Insulina de Acción Prolongada/administración & dosificación , Insulina de Acción Prolongada/uso terapéutico , Células Secretoras de Insulina/metabolismo , Japón , Masculino , Proinsulina/sangre , Pirazinas/administración & dosificación , Fosfato de Sitagliptina , Triazoles/administración & dosificaciónRESUMEN
The aim of the present study was to evaluate the effect of insulin glargine (Gla) (as part of basal-supported oral therapy) on endogenous insulin secretion and beta-cell function in type 2 diabetic patients. In 33 insulin-naive patients showing poor glycemic control on treatment with sulfonylurea (SU)-based OADs without DPP4 inhibitors, once-daily injection of Gla was added without changing OADs, and the dose of Gla was titrated to attain a fasting plasma glucose (FPG) <110 mg/dL over 24 weeks. Morning meal tests were done at baseline, 12 weeks and 24 weeks. FPG and 2-hour plasma glucose (2HPG) and serum C-peptide (FCPR and 2HCPR) were measured 3 times, while serum intact proinsulin (FPI and 2HPI) was measured at baseline and 24 weeks. Levels of FPG, FCPR, 2HPG, and HbA1c were significantly reduced from baseline at 24 weeks (176±52 to 117±27 mg/dL, p<0.01; 2.0±0.9 to 1.6±1.0 ng/mL, p<0.01; 257±53 to 202±27 mg/dL, p<0.01; and 8.4±0.9 to 7.3±0.6%, p<0.01, Mean±SD), but 2HCPR was unchanged. The patients were divided into two groups depending on whether FPG at 24 weeks was <110 mg/dL or not: attained group (n=15) and not attained group (n=18). The dose of Gla did not differ between the two groups, but the 2HPI/2HCPR ratio at 24 weeks showed a significant decrease from baseline in the attained group. Supplementation with Gla improved glycemic control and maintained intrinsic basal insulin secretion, without changing 2-hour postprandial secretion. Achieving good glycemic control with an FPG<110 mg/dL by adding Gla decreased the 2HPI/2HCPR ratio at 24 weeks.
Asunto(s)
Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipoglucemiantes/administración & dosificación , Insulina de Acción Prolongada/administración & dosificación , Células Secretoras de Insulina/efectos de los fármacos , Células Secretoras de Insulina/fisiología , Insulina/metabolismo , Anciano , Glucemia/análisis , Péptido C/sangre , Ayuno , Femenino , Hemoglobina Glucada/análisis , Humanos , Insulina Glargina , Secreción de Insulina , Japón , Masculino , Persona de Mediana Edad , Periodo Posprandial , Compuestos de Sulfonilurea/administración & dosificaciónRESUMEN
Insulin glulisine (Glu) is a rapidly-acting insulin analog with a faster onset of action than the other insulin analogs of its class, which are insulin aspart (Asp) and insulin lispro (Lisp). While insulin Glu is usually injected just before meals, postprandial injection may help to avoid unexpected postprandial hypoglycemia or hyperglycemia by adjusting the insulin dosage according to food intake. However, the effect of postprandial insulin Glu on the glucose profile has not been evaluated. The aim of this study was to compare daily glucose excursion by continuous glucose monitoring (CGM) between multiple daily doses of preprandial insulin Asp or postprandial insulin Glu. In a randomized cross-over trial, we performed CGM to evaluate the 48-hour glucose profile during treatment with the same dosage of insulin Asp just before each meal in 12 hospitalized patients with type 2 diabetes. Patients also received the same dosage of long-acting insulin glargine at bedtime. The average glucose level, standard deviation of the glucose level, mean amplitude of glucose excursion, and daily glucose profile did not differ between preprandial Asp and postprandial Glu. The incidence of hypoglycemic episodes (glucose level<70 mg/dL with or without symptoms) and the area under the curve of glucose<70 mg/dL also did not differ between the two insulin regimens. Multiple daily injections of preprandial Asp and postprandial Glu achieved the same daily glucose excursion profile. Postprandial injection of Glu may provide greater flexibility for patients who require insulin therapy.
Asunto(s)
Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hiperglucemia/prevención & control , Hipoglucemia/prevención & control , Hipoglucemiantes/uso terapéutico , Insulina Aspart/uso terapéutico , Insulina/análogos & derivados , Adulto , Anciano , Glucemia/análisis , Estudios Cruzados , Complicaciones de la Diabetes/prevención & control , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/complicaciones , Esquema de Medicación , Quimioterapia Combinada/efectos adversos , Femenino , Hemoglobina Glucada/análisis , Humanos , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/efectos adversos , Insulina/administración & dosificación , Insulina/efectos adversos , Insulina/uso terapéutico , Insulina Aspart/administración & dosificación , Insulina Aspart/efectos adversos , Insulina Glargina , Insulina de Acción Prolongada/administración & dosificación , Insulina de Acción Prolongada/uso terapéutico , Masculino , Persona de Mediana Edad , Monitoreo AmbulatorioRESUMEN
UNLABELLED: Aims/Introduction: Biphasic insulin aspart 30 (BIAsp 30) has an earlier and stronger peak effect with a similar duration of action to biphasic human insulin 30 (BHI 30). However, direct comparison of daily glucose excursion during treatment with these two types of insulin has not been carried out. MATERIALS AND METHODS: We carried out continuous glucose monitoring (CGM) and evaluated the 48-h glucose profile during twice-daily injections of BIAsp 30 or BHI 30 at the same dosage in 12 hospitalized patients with type 2 diabetes who participated in a randomized cross-over trial. RESULTS: The 48-h average glucose level and mean amplitude of glucose excursion (MAGE) were lower during BIAsp 30 treatment than with BHI 30. The average glucose level during 2-3 h after breakfast and 2-4 h after dinner, and the incremental postprandial glucose from just before to 4 h after dinner were lower with BIAsp 30 treatment than with BHI 30. Furthermore, BIAsp 30 treatment reduced the SD from 30 min before to 4 h after breakfast and lunch compared with BHI 30. The average glucose level and SD during the 30 min before each meal and during the night were not different between the two insulin preparations, and hypoglycemia was not observed with either treatment. CONCLUSIONS: Twice-daily BIAsp 30 reduced the 48-h average glucose and MAGE, the postprandial glucose (after breakfast and dinner), and the SD of glucose excursion (after breakfast and lunch) compared with the same dosage of BHI 30, without causing hypoglycemia or deterioration of glycemic control before meals and at night. This trial was registered with UMIN (no. UMIN000005129). (J Diabetes Invest, doi: 10.1111/j.2040-1124.2011.00123.x, 2011).