Faidon Magkos1, Michelle H Lee2, Maybritte Lim2, Alex R Cook3, Vanna Chhay4, Tze Ping Loh5, Kee Seng Chia3, Sonia Baig2, Ian Yi Han Ang3, Joanne Y Y Tay6, Chin Meng Khoo7, Jeffrey B Halter8, Sue-Anne Toh9. 1. Department of Nutrition, Exercise and Sports, University of Copenhagen, Denmark. 2. Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. 3. Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore. 4. Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. 5. Department of Laboratory Medicine, National University Hospital, Singapore. 6. NOVI Health, Singapore. 7. Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Department of Medicine, National University Hospital, Singapore. 8. Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Division of Geriatric and Palliative Medicine, University of Michigan, USA. 9. Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; NOVI Health, Singapore; Department of Medicine, National University Hospital, Singapore; Regional Health System Office, National University Health System, Singapore; Singapore Population HEalth ImpRovement Centre (SPHERiC), National University Health System, Singapore. Electronic address: mdcsates@nus.edu.sg.
Abstract
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.
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.