RESUMEN
AIMS: To investigate the effect on glycaemic control of adding glimepiride to on-going treatment with metformin and insulin in patients with known diabetes more than 10 years. METHODS: Glimepiride 4 mg or placebo was added in randomised order for three months with a washout period of 6 weeks. All insulin regimens were allowed. Insulin doses were reduced if considered necessary. Continuous glucose monitoring was performed at the end of each period. RESULTS: Forty-three patients, median age 66 years (46-74), diabetes duration 16 (10-30), BMI 30 kg/m(2) (25-37) and mean HbA1c 7.1% NGSP, (64 mmol/mol IFCC) were randomised. With placebo there was no change in HbA1c while a decrease of 0.6%, (7 mmol/mol IFCC) (P < 0.001), was observed with glimepiride even though insulin doses had to be reduced in 23 patients (median change 29%, range 2-100%). Minor hypoglycaemia was reported but no severe hypoglycaemic event was observed. The ratio between C-peptide/glucose increased significantly (P < 0.001) with glimepiride, both fasting and postprandially and, in a stepwise multiple regression analysis of possible predictive factors for response, a more pronounced decrease in HbA1c was associated with the magnitude of the increment in C-peptide/glucose. Older age was associated with a smaller response. Twenty-nine patients (67%) were defined as responders if this was defined as an HbA1c decrease ≥0.5% (5 mmol/mol IFCC) or an insulin dose reduction ≥20%. CONCLUSIONS: Even after long duration of diabetes, addition of glimepiride to insulin and metformin can be effective in lowering HbA1c and/or reducing the need for exogenous insulin.
Asunto(s)
Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Insulina/uso terapéutico , Metformina/uso terapéutico , Compuestos de Sulfonilurea/uso terapéutico , Anciano , Glucemia , Estudios Cruzados , Método Doble Ciego , Quimioterapia Combinada , Ayuno , Femenino , Humanos , Masculino , Persona de Mediana Edad , Periodo Posprandial , Resultado del TratamientoRESUMEN
AIM: The present study aimed to describe changes over 10 years in HbA(1c) and beta-cell function, as assessed by postprandial C-peptide (PP-CPT) and C-peptide/glucose (PP-CPT/glucose) ratio, and to investigate whether treatment with sulphonylurea (SU) exerts a deleterious effect on beta-cell function. METHODS: During 1997-1998, HbA(1c), PP-CPT and PP glucose were measured in 462 patients. Ten years later, 171 of the 341 patients who were still alive were followed-up. RESULTS: HbA(1c) decreased from 7.41 to 6.96% (P=0.002) as treatments were intensified. There was a decrease in both PP-CPT (P<0.001) and PP-CPT/glucose ratio (P=0.063). A multivariable-regression model was used to evaluate the effects on beta-cell function changes, using the following variables as effect modifiers: gender; age; BMI; diabetes duration; baseline PP-CPT/glucose ratio; HbA(1c); GAD-antibody class; and SU treatment (continuously, periodically, never). Baseline PP-CPT/glucose ratio was the most important variable (R(2)=45%; P<0.001) for explaining variations in beta-cell function. An increase in HbA(1c) was associated with a decrease in beta-cell function, and beta-cell function remained unchanged if glycaemic control was improved. Long-term treatment with SU had no effect on long-term changes in beta-cell function (R(2)=0.1%; P=0.894). CONCLUSION: Both HbA(1c) and beta-cell function decreased over 10 years with SU treatment, but such treatment was not associated with a pronounced decline in beta-cell function. These results, however, need to be interpreted with caution, as this was an observational study. Nevertheless, the present study findings do not support the notion that SU, as used in clinical practice, is harmful to beta-cell function.
Asunto(s)
Péptido C/sangre , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hemoglobina Glucada/análisis , Células Secretoras de Insulina/efectos de los fármacos , Compuestos de Sulfonilurea/efectos adversos , Adulto , Anciano , Anciano de 80 o más Años , Glucemia/análisis , Índice de Masa Corporal , Femenino , Humanos , Células Secretoras de Insulina/fisiología , Masculino , Persona de Mediana Edad , Periodo Posprandial , Análisis de Regresión , Compuestos de Sulfonilurea/uso terapéutico , Factores de TiempoRESUMEN
AIMS: To assess the effect of sulphonylurea (SU) in patients with Type 2 diabetes undergoing long-term combination therapy with insulin, by withdrawal of SU, and to identify clinically useful markers of long-term response. METHODS: We studied 25 patients, aged 59-83 years, mean glycated haemoglobin (HbA(1c)) 7.0 +/- 0.6%, who had been treated with SU for 16 years (7-24 years) in combination with insulin for 10 years (6-15 years). After basal measurements, SU was withdrawn. Fasting plasma glucose (FPG) and C-peptide were then monitored every 2-3 days during the following 2 weeks. If FPG increased > 40% or P-glucose exceeded 20 mmol/l, SU was restarted. If neither criterion was met, a clinical follow-up visit with measurement of HbA(1c) was scheduled within 8 weeks. RESULTS: Twenty patients were restarted on SU because of worsening glycaemic control, eight within the first 4 weeks and the remaining 12 at the follow-up visit as their HbA(1c) had increased by 1.1% (range 0.4-2.0%). All these patients were defined as 'SU responders'. The increase in FPG during the initial 2 weeks correlated positively with duration of diabetes (P < 0.01) and duration of SU treatment (P < 0.001). The 'SU responders' had higher levels of basal fasting C-peptide (0.84 +/- 0.44 vs. 0.41 +/- 0.15 nmol/l, P < 0.05), but the variation was wide and none of the measured variables identified 'SU responders'. CONCLUSIONS: In 80% of this group of patients, glycaemic control deteriorated after SU withdrawal despite long duration of SU treatment.
Asunto(s)
Glucemia/metabolismo , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hemoglobina Glucada/análisis , Hipoglucemiantes/uso terapéutico , Insulina/uso terapéutico , Compuestos de Sulfonilurea/administración & dosificación , Anciano , Anciano de 80 o más Años , Péptido C/sangre , Diabetes Mellitus Tipo 2/sangre , Quimioterapia Combinada , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Compuestos de Sulfonilurea/uso terapéuticoRESUMEN
OBJECTIVE: To evaluate the accuracy of nocturnal continuous glucose monitoring by CGMS. RESEARCH DESIGN AND METHODS: A CGMS was inserted in 14 type 2 diabetic patients on combined oral and insulin therapy at altogether 15 occasions. During the second (48 hours) and third (72 hours) night of registration each subject was observed and plasma glucose was analysed seven times during the night by venous sampling and compared to CGMS. These venous values were not used for calibration of the sensor. Pairs of data were analysed using correlation coefficient, Bland-Altman graphs and Clarke Error Grid analysis. RESULTS: 32% of CGMS data did not meet the quality criteria for optimal accuracy and were excluded. A correlation coefficient of 0.80 (p < 0.0001) was seen after 48 hours and a lower coefficient of 0.33 (p = 0.0082) after 72 hours. Bland-Altman analyses demonstrated that the dispersion of the values around the mean of differences was wider after 72 hours as compared to after 48 hours. In the Clark Error Grid analysis 100% of data were within zones A and B after 48 hours, with 60% in zone A. After 72 hours only 44% were in zone A and 7% of data were in the clinically unacceptable zone D. CONCLUSION: The MiniMed Medtronic CGMS has acceptable nocturnal accuracy after 48 hours of registration, but the accuracy thereafter deteriorates with time, implicating that the CGMS thereafter may prove less useful for nocturnal monitoring.