RESUMO
OBJECTIVE: To compare the long-term effects of glucose-lowering medications (insulin glargine U-100, glimepiride, liraglutide, and sitagliptin) when added to metformin on insulin sensitivity and ß-cell function. RESEARCH DESIGN AND METHODS: In the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE) cohort with type 2 diabetes (n = 4,801), HOMA2 was used to estimate insulin sensitivity (HOMA2-%S) and fasting ß-cell function (HOMA2-%B) at baseline and 1, 3, and 5 years on treatment. Oral glucose tolerance test ß-cell responses (C-peptide index [CPI] and total C-peptide response [incremental C-peptide/incremental glucose over 120 min]) were evaluated at the same time points. These responses adjusted for HOMA2-%S in regression analysis provided estimates of ß-cell function. RESULTS: HOMA2-%S increased from baseline to year 1 with glargine and remained stable thereafter, while it did not change from baseline in the other treatment groups. HOMA2-%B and C-peptide responses were increased to variable degrees at year 1 in all groups but then declined progressively over time. At year 5, CPI was similar between liraglutide and sitagliptin, and higher for both than for glargine and glimepiride [0.80, 0.87, 0.74, and 0.64 (nmol/L)/(mg/dL) * 100, respectively; P < 0.001], while the total C-peptide response was greatest with liraglutide, followed in descending order by sitagliptin, glargine, and glimepiride [1.54, 1.25, 1.02, and 0.87 (nmol/L)/(mg/dL) * 100, respectively, P < 0.001]. After adjustment for HOMA2-%S to obtain an estimate of ß-cell function, the nature of the change in ß-cell responses reflected those in ß-cell function. CONCLUSIONS: The differential long-term effects on insulin sensitivity and ß-cell function of four different glucose-lowering medications when added to metformin highlight the importance of the loss of ß-cell function in the progression of type 2 diabetes.
Assuntos
Diabetes Mellitus Tipo 2 , Resistência à Insulina , Metformina , Compostos de Sulfonilureia , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Insulina Glargina/uso terapêutico , Hipoglicemiantes/uso terapêutico , Glucose/uso terapêutico , Liraglutida/farmacologia , Liraglutida/uso terapêutico , Resistência à Insulina/fisiologia , Peptídeo C , Glicemia , Metformina/uso terapêutico , Fosfato de Sitagliptina/uso terapêuticoRESUMO
OBJECTIVE: We investigated sex and racial differences in insulin sensitivity, ß-cell function, and glycated hemoglobin (HbA1c) and the associations with selected phenotypic characteristics. RESEARCH DESIGN AND METHODS: This is a cross-sectional analysis of baseline data from 3,108 GRADE (Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study) participants. All had type 2 diabetes diagnosed <10 years earlier and were on metformin monotherapy. Insulin sensitivity and ß-cell function were evaluated using the HOMA of insulin sensitivity and estimates from oral glucose tolerance tests, including the Matsuda Index, insulinogenic index, C-peptide index, and oral disposition index (DI). RESULTS: The cohort was 56.6 ± 10 years of age (mean ± SD), 63.8% male, with BMI 34.2 ± 6.7 kg/m2, HbA1c 7.5 ± 0.5%, and type 2 diabetes duration 4.0 ± 2.8 years. Women had higher DI than men but similar insulin sensitivity. DI was the highest in Black/African Americans, followed by American Indians/Alaska Natives, Asians, and Whites in descending order. Compared with Whites, American Indians/Alaska Natives had significantly higher HbA1c, but Black/African Americans and Asians had lower HbA1c. However, when adjusted for glucose levels, Black/African Americans had higher HbA1c than Whites. Insulin sensitivity correlated inversely with BMI, waist-to-hip ratio, triglyceride-to-HDL-cholesterol ratio (TG/HDL-C), and the presence of metabolic syndrome, whereas DI was associated directly with age and inversely with BMI, HbA1c, and TG/HDL-C. CONCLUSIONS: In the GRADE cohort, ß-cell function differed by sex and race and was associated with the concurrent level of HbA1c. HbA1c also differed among the races, but not by sex. Age, BMI, and TG/HDL-C were associated with multiple measures of ß-cell function and insulin sensitivity.
Assuntos
Diabetes Mellitus Tipo 2 , Resistência à Insulina , Glicemia , Peptídeo C , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Lactente , Insulina , MasculinoRESUMO
Transitioning from the inpatient to outpatient setting is often a problematic aspect of diabetes mellitus (DM) care. Different factors during hospitalization may adversely affect glycemic control in patients, who are frequently discharged on regimens that differ markedly from prehospitalization outpatient regimens. Moreover, the discharge recommendations may not have been tested adequately during a relatively short hospital length of stay and pose a significant threat to patient safety upon discharge. Our pilot study evaluated the effect on hospital utilization of the transitional care clinic (TCC), where patients with DM are seen within 2 to 5 days of hospital discharge. One hundred patients with DM, who were either medically indigent (no insurance or Medicaid and no primary care providers) or covered by Medicaid, and who did not have a primary care provider, were randomized into either a control or an intervention group upon discharge from the hospital. Subjects from the intervention group (n = 50) were seen in the TCC. All subjects were contacted 90 days after discharge to collect information about emergency department visits and readmissions. Thirteen subjects from the control group and 13 from the intervention group visited the emergency department within 90 days of discharge. Fourteen control subjects (28%) and 10 intervention patients (20%) were rehospitalized for various medical conditions during the follow-up period (P = not significant). Among patients originally admitted for DM-related issues, 6 of 14 in the control group (42.9%) and 2 out of 16 in the intervention group (12.5%) were readmitted during follow-up (P < 0.05). We conclude that the TCC may be effective for the prevention of rehospitalizations in indigent patients admitted for DM-related problems and who did not have primary care providers. The benefit of the TCC was not seen when patients with DM were admitted for other medical problems. Larger randomized controlled trials are needed to confirm this preliminary finding.