Dynamic assessment of insulin secretion and insulin resistance in Asians with prediabetes
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Dynamic assessment of insulin secretion and insulin resistance in Asians with prediabetes. / Magkos, Faidon; Lee, Michelle H; Lim, Maybritte; Cook, Alex R; Chhay, Vanna; Loh, Tze Ping; Chia, Kee Seng; Baig, Sonia; Ang, Ian Yi Han; Tay, Joanne Y Y; Khoo, Chin Meng; Halter, Jeffrey B; Toh, Sue-Anne.
In: Metabolism, Vol. 128, 154957, 2022.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Dynamic assessment of insulin secretion and insulin resistance in Asians with prediabetes
AU - Magkos, Faidon
AU - Lee, Michelle H
AU - Lim, Maybritte
AU - Cook, Alex R
AU - Chhay, Vanna
AU - Loh, Tze Ping
AU - Chia, Kee Seng
AU - Baig, Sonia
AU - Ang, Ian Yi Han
AU - Tay, Joanne Y Y
AU - Khoo, Chin Meng
AU - Halter, Jeffrey B
AU - Toh, Sue-Anne
N1 - Copyright © 2021. Published by Elsevier Inc.
PY - 2022
Y1 - 2022
N2 - Aims/hypothesis: Prediabetes and type 2 diabetes are highly prevalent in Asia. Understanding the pathophysiology of abnormal glucose homeostasis in Asians will have important implications for reducing disease burden, but there have been conflicting reports on the relative contributions of insulin secretion and action in disease progression. In this study, we aimed to assess the contribution of β-cell dysfunction and insulin resistance in the Asian prediabetes phenotype.Methods: We recruited 1679 Asians with prediabetes (n = 659) or normoglycemia (n = 1020) from a multi-ethnic population in Singapore. Participants underwent an oral glucose tolerance test, an intravenous glucose challenge, and a hyperinsulinemic-euglycemic clamp procedure to determine glucose tolerance, β-cell responsivity, insulin secretion, insulin clearance and insulin sensitivity.Results: Participants with prediabetes had significantly higher glucose concentrations in the fasting state and after glucose ingestion than did normoglycemic participants. Insulin sensitivity (M/I ratio) was ~15% lower, acute insulin response (AIR) to intravenous glucose and β-cell responsivity to oral glucose were ~35% lower, but total insulin secretion rate in the fasting state and after glucose ingestion was ~10% greater in prediabetic than in normoglycemic participants. The decrease in β-cell function with worsening glucose homeostasis in Asians with prediabetes was associated with progressively greater defects in AIR rather than M/I. However, analysis using static surrogate measures (HOMA indices) of insulin resistance and β-cell function revealed a different pattern.Conclusions: Lower AIR to intravenous glucose and β-cell responsivity to oral glucose, on a background of mild insulin resistance, are the major contributors to the dysregulation of glucose homeostasis in Asians with prediabetes.
AB - Aims/hypothesis: Prediabetes and type 2 diabetes are highly prevalent in Asia. Understanding the pathophysiology of abnormal glucose homeostasis in Asians will have important implications for reducing disease burden, but there have been conflicting reports on the relative contributions of insulin secretion and action in disease progression. In this study, we aimed to assess the contribution of β-cell dysfunction and insulin resistance in the Asian prediabetes phenotype.Methods: We recruited 1679 Asians with prediabetes (n = 659) or normoglycemia (n = 1020) from a multi-ethnic population in Singapore. Participants underwent an oral glucose tolerance test, an intravenous glucose challenge, and a hyperinsulinemic-euglycemic clamp procedure to determine glucose tolerance, β-cell responsivity, insulin secretion, insulin clearance and insulin sensitivity.Results: Participants with prediabetes had significantly higher glucose concentrations in the fasting state and after glucose ingestion than did normoglycemic participants. Insulin sensitivity (M/I ratio) was ~15% lower, acute insulin response (AIR) to intravenous glucose and β-cell responsivity to oral glucose were ~35% lower, but total insulin secretion rate in the fasting state and after glucose ingestion was ~10% greater in prediabetic than in normoglycemic participants. The decrease in β-cell function with worsening glucose homeostasis in Asians with prediabetes was associated with progressively greater defects in AIR rather than M/I. However, analysis using static surrogate measures (HOMA indices) of insulin resistance and β-cell function revealed a different pattern.Conclusions: Lower AIR to intravenous glucose and β-cell responsivity to oral glucose, on a background of mild insulin resistance, are the major contributors to the dysregulation of glucose homeostasis in Asians with prediabetes.
KW - Faculty of Science
KW - Asian prediabetes
KW - Insulin secretion
KW - Insulin sensitivity
KW - Hyperinsulinemic-euglycemic clamp
KW - Acute insulin response
KW - Oral glucose minimal modeling
U2 - 10.1016/j.metabol.2021.154957
DO - 10.1016/j.metabol.2021.154957
M3 - Journal article
C2 - 34942192
VL - 128
JO - Metabolism
JF - Metabolism
SN - 0026-0495
M1 - 154957
ER -
ID: 288857162