Diabetes, obesity & metabolism · 2022
Type 2 diabetes subgroups and response to glucose-lowering therapy: Results from the EDICT and Qatar studies.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Abdul-Ghani Tamam, Puckett Curtiss, Migahid Osama, Abdelgani Siham, Migahed Ayman, Adams John, Triplitt Curtis, DeFronzo Ralph, Jayyousi Amin, Abdul-Ghani Muhammad
Аннотация
AIM: To examine the efficacy of glucose-lowering medications in subgroups of patients with type 2 diabetes mellitus (T2DM).
RESEARCH DESIGN AND METHODS: Cluster analysis was performed in participants in the Efficacy and Durability of Initial Combination Therapy for Type 2 Diabetes (EDICT) study and the Qatar study using age, body mass index (BMI), glycated haemoglobin (HbA1c), and homeostatic model assessment of insulin resistance (HOMA-IR) and beta-cell function (HOMA-β). Participants also underwent an oral glucose tolerance test with measurement of plasma glucose, insulin and C-peptide concentrations to derive independent measures of insulin secretion and insulin sensitivity. The response to glucose-lowering therapies (change in HbA1c) was measured in each participant cluster for 3 years.
RESULTS: Three distinct and comparable clusters/groups of T2DM patients were identified in both the EDICT and Qatar studies. Participants in Group 1 had the highest HbA1c and manifested severe insulin deficiency. Participants in Group 3 had comparable insulin sensitivity to those in Group 1 but better beta-cell function and better glucose control. Participants in Group 2 had the highest BMI with severe insulin resistance accompanied by marked hyperinsulinaemia, which was primarily attributable to decreased insulin clearance. Unexpectedly, participants in Group 1 had better response to combination therapy with pioglitazone plus exenatide than with insulin therapy or metformin sequentially followed by glipizide and basal insulin, while participants in Group 2 responded equally well to both therapies despite very severe insulin resistance.
CONCLUSION: Distinct metabolic phenotypes characterize different T2DM clusters and differential responses to glucose-lowering therapies. Participants with severe insulin deficiency respond better to agents that preserve beta-cell function, while, surprisingly, patients with severe insulin resistance did not respond favourably to insulin sensitizers.
RESEARCH DESIGN AND METHODS: Cluster analysis was performed in participants in the Efficacy and Durability of Initial Combination Therapy for Type 2 Diabetes (EDICT) study and the Qatar study using age, body mass index (BMI), glycated haemoglobin (HbA1c), and homeostatic model assessment of insulin resistance (HOMA-IR) and beta-cell function (HOMA-β). Participants also underwent an oral glucose tolerance test with measurement of plasma glucose, insulin and C-peptide concentrations to derive independent measures of insulin secretion and insulin sensitivity. The response to glucose-lowering therapies (change in HbA1c) was measured in each participant cluster for 3 years.
RESULTS: Three distinct and comparable clusters/groups of T2DM patients were identified in both the EDICT and Qatar studies. Participants in Group 1 had the highest HbA1c and manifested severe insulin deficiency. Participants in Group 3 had comparable insulin sensitivity to those in Group 1 but better beta-cell function and better glucose control. Participants in Group 2 had the highest BMI with severe insulin resistance accompanied by marked hyperinsulinaemia, which was primarily attributable to decreased insulin clearance. Unexpectedly, participants in Group 1 had better response to combination therapy with pioglitazone plus exenatide than with insulin therapy or metformin sequentially followed by glipizide and basal insulin, while participants in Group 2 responded equally well to both therapies despite very severe insulin resistance.
CONCLUSION: Distinct metabolic phenotypes characterize different T2DM clusters and differential responses to glucose-lowering therapies. Participants with severe insulin deficiency respond better to agents that preserve beta-cell function, while, surprisingly, patients with severe insulin resistance did not respond favourably to insulin sensitizers.