β-cell function in subjects spanning the range from normal glucose tolerance to overt diabetes

A new analysis

Ele Ferrannini, Amalia Gastaldelli, Yoshinori Miyazaki, Masafumi Matsuda, Andrea Mari, Ralph A Defronzo

Research output: Contribution to journalArticle

343 Citations (Scopus)

Abstract

The nature of the progressive β-cell failure occurring as normal glucose tolerant (NGT) individuals progress to type 2 diabetes (T2DM) is incompletely understood. We measured insulin sensitivity (by a euglycemic insulin clamp) and insulin secretion rate (by deconvolution of plasma C-peptide levels during an oral glucose tolerance test) in 188 subjects [19 lean NGT (body mass indes [BMI] ≤ 25 kg/m2), 42 obese NGT, 22 BMI-matched impaired glucose tolerance [IGT], and 105 BMI-matched T2DM]. Main determinants of β-cell function on the oral glucose tolerance test were derived from a mathematical model featuring the following: 1) glucose concentration-insulin secretion dose response (glucose sensitivity), 2) a secretion component proportional to the derivative of plasma glucose concentration (rate sensitivity); and 3) a potentiation factor. When NGT and T2DM were subgrouped by 2-h plasma glucose concentrations, insulin secretion rate revealed an inverted U-shaped pattern, rising through NGT up to IGT and falling off thereafter. In contrast, β-cell glucose sensitivity dropped in a monophasic, curvilinear fashion throughout the range of 2-h plasma glucose. Within the NGT range (2-h glucose of 4.1-7.7 mmol/liter), β-cell glucose sensitivity declined by 50-70% (P < 0.02). Insulin sensitivity decreased sharply in the transition from lean to obese NGT and then declined further in IGT and mild T2DM to level off in the higher three quartiles of diabetic hyperglycemia. In T2DM, defective β-cell potentiation and rate sensitivity also emerged (P ≤ 0.05). In the whole data set, insulin sensitivity and the dynamic parameters of β-cell function explained 89% of the variability of 2-h plasma glucose levels. The following conclusions were reached: 1) β-cell glucose sensitivity falls already within the NGT range in association with rising 2-h plasma glucose concentrations, although absolute insulin secretion rates increase; and 2) throughout the glucose tolerance range, dynamic parameters of β-cell function (glucose sensitivity, rate sensitivity, and potentiation) and insulin sensitivity are independent determinants of 2-h plasma glucose levels.

Original languageEnglish (US)
Pages (from-to)493-500
Number of pages8
JournalJournal of Clinical Endocrinology and Metabolism
Volume90
Issue number1
DOIs
StatePublished - Jan 2005

Fingerprint

Medical problems
Reference Values
Glucose
Insulin
Plasmas
Glucose Intolerance
Insulin Resistance
Glucose Tolerance Test
Glucose Clamp Technique
C-Peptide

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

β-cell function in subjects spanning the range from normal glucose tolerance to overt diabetes : A new analysis. / Ferrannini, Ele; Gastaldelli, Amalia; Miyazaki, Yoshinori; Matsuda, Masafumi; Mari, Andrea; Defronzo, Ralph A.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 90, No. 1, 01.2005, p. 493-500.

Research output: Contribution to journalArticle

Ferrannini, Ele ; Gastaldelli, Amalia ; Miyazaki, Yoshinori ; Matsuda, Masafumi ; Mari, Andrea ; Defronzo, Ralph A. / β-cell function in subjects spanning the range from normal glucose tolerance to overt diabetes : A new analysis. In: Journal of Clinical Endocrinology and Metabolism. 2005 ; Vol. 90, No. 1. pp. 493-500.
@article{912907f6a82a4d999561911f1536c53c,
title = "β-cell function in subjects spanning the range from normal glucose tolerance to overt diabetes: A new analysis",
abstract = "The nature of the progressive β-cell failure occurring as normal glucose tolerant (NGT) individuals progress to type 2 diabetes (T2DM) is incompletely understood. We measured insulin sensitivity (by a euglycemic insulin clamp) and insulin secretion rate (by deconvolution of plasma C-peptide levels during an oral glucose tolerance test) in 188 subjects [19 lean NGT (body mass indes [BMI] ≤ 25 kg/m2), 42 obese NGT, 22 BMI-matched impaired glucose tolerance [IGT], and 105 BMI-matched T2DM]. Main determinants of β-cell function on the oral glucose tolerance test were derived from a mathematical model featuring the following: 1) glucose concentration-insulin secretion dose response (glucose sensitivity), 2) a secretion component proportional to the derivative of plasma glucose concentration (rate sensitivity); and 3) a potentiation factor. When NGT and T2DM were subgrouped by 2-h plasma glucose concentrations, insulin secretion rate revealed an inverted U-shaped pattern, rising through NGT up to IGT and falling off thereafter. In contrast, β-cell glucose sensitivity dropped in a monophasic, curvilinear fashion throughout the range of 2-h plasma glucose. Within the NGT range (2-h glucose of 4.1-7.7 mmol/liter), β-cell glucose sensitivity declined by 50-70{\%} (P < 0.02). Insulin sensitivity decreased sharply in the transition from lean to obese NGT and then declined further in IGT and mild T2DM to level off in the higher three quartiles of diabetic hyperglycemia. In T2DM, defective β-cell potentiation and rate sensitivity also emerged (P ≤ 0.05). In the whole data set, insulin sensitivity and the dynamic parameters of β-cell function explained 89{\%} of the variability of 2-h plasma glucose levels. The following conclusions were reached: 1) β-cell glucose sensitivity falls already within the NGT range in association with rising 2-h plasma glucose concentrations, although absolute insulin secretion rates increase; and 2) throughout the glucose tolerance range, dynamic parameters of β-cell function (glucose sensitivity, rate sensitivity, and potentiation) and insulin sensitivity are independent determinants of 2-h plasma glucose levels.",
author = "Ele Ferrannini and Amalia Gastaldelli and Yoshinori Miyazaki and Masafumi Matsuda and Andrea Mari and Defronzo, {Ralph A}",
year = "2005",
month = "1",
doi = "10.1210/jc.2004-1133",
language = "English (US)",
volume = "90",
pages = "493--500",
journal = "Journal of Clinical Endocrinology and Metabolism",
issn = "0021-972X",
publisher = "The Endocrine Society",
number = "1",

}

TY - JOUR

T1 - β-cell function in subjects spanning the range from normal glucose tolerance to overt diabetes

T2 - A new analysis

AU - Ferrannini, Ele

AU - Gastaldelli, Amalia

AU - Miyazaki, Yoshinori

AU - Matsuda, Masafumi

AU - Mari, Andrea

AU - Defronzo, Ralph A

PY - 2005/1

Y1 - 2005/1

N2 - The nature of the progressive β-cell failure occurring as normal glucose tolerant (NGT) individuals progress to type 2 diabetes (T2DM) is incompletely understood. We measured insulin sensitivity (by a euglycemic insulin clamp) and insulin secretion rate (by deconvolution of plasma C-peptide levels during an oral glucose tolerance test) in 188 subjects [19 lean NGT (body mass indes [BMI] ≤ 25 kg/m2), 42 obese NGT, 22 BMI-matched impaired glucose tolerance [IGT], and 105 BMI-matched T2DM]. Main determinants of β-cell function on the oral glucose tolerance test were derived from a mathematical model featuring the following: 1) glucose concentration-insulin secretion dose response (glucose sensitivity), 2) a secretion component proportional to the derivative of plasma glucose concentration (rate sensitivity); and 3) a potentiation factor. When NGT and T2DM were subgrouped by 2-h plasma glucose concentrations, insulin secretion rate revealed an inverted U-shaped pattern, rising through NGT up to IGT and falling off thereafter. In contrast, β-cell glucose sensitivity dropped in a monophasic, curvilinear fashion throughout the range of 2-h plasma glucose. Within the NGT range (2-h glucose of 4.1-7.7 mmol/liter), β-cell glucose sensitivity declined by 50-70% (P < 0.02). Insulin sensitivity decreased sharply in the transition from lean to obese NGT and then declined further in IGT and mild T2DM to level off in the higher three quartiles of diabetic hyperglycemia. In T2DM, defective β-cell potentiation and rate sensitivity also emerged (P ≤ 0.05). In the whole data set, insulin sensitivity and the dynamic parameters of β-cell function explained 89% of the variability of 2-h plasma glucose levels. The following conclusions were reached: 1) β-cell glucose sensitivity falls already within the NGT range in association with rising 2-h plasma glucose concentrations, although absolute insulin secretion rates increase; and 2) throughout the glucose tolerance range, dynamic parameters of β-cell function (glucose sensitivity, rate sensitivity, and potentiation) and insulin sensitivity are independent determinants of 2-h plasma glucose levels.

AB - The nature of the progressive β-cell failure occurring as normal glucose tolerant (NGT) individuals progress to type 2 diabetes (T2DM) is incompletely understood. We measured insulin sensitivity (by a euglycemic insulin clamp) and insulin secretion rate (by deconvolution of plasma C-peptide levels during an oral glucose tolerance test) in 188 subjects [19 lean NGT (body mass indes [BMI] ≤ 25 kg/m2), 42 obese NGT, 22 BMI-matched impaired glucose tolerance [IGT], and 105 BMI-matched T2DM]. Main determinants of β-cell function on the oral glucose tolerance test were derived from a mathematical model featuring the following: 1) glucose concentration-insulin secretion dose response (glucose sensitivity), 2) a secretion component proportional to the derivative of plasma glucose concentration (rate sensitivity); and 3) a potentiation factor. When NGT and T2DM were subgrouped by 2-h plasma glucose concentrations, insulin secretion rate revealed an inverted U-shaped pattern, rising through NGT up to IGT and falling off thereafter. In contrast, β-cell glucose sensitivity dropped in a monophasic, curvilinear fashion throughout the range of 2-h plasma glucose. Within the NGT range (2-h glucose of 4.1-7.7 mmol/liter), β-cell glucose sensitivity declined by 50-70% (P < 0.02). Insulin sensitivity decreased sharply in the transition from lean to obese NGT and then declined further in IGT and mild T2DM to level off in the higher three quartiles of diabetic hyperglycemia. In T2DM, defective β-cell potentiation and rate sensitivity also emerged (P ≤ 0.05). In the whole data set, insulin sensitivity and the dynamic parameters of β-cell function explained 89% of the variability of 2-h plasma glucose levels. The following conclusions were reached: 1) β-cell glucose sensitivity falls already within the NGT range in association with rising 2-h plasma glucose concentrations, although absolute insulin secretion rates increase; and 2) throughout the glucose tolerance range, dynamic parameters of β-cell function (glucose sensitivity, rate sensitivity, and potentiation) and insulin sensitivity are independent determinants of 2-h plasma glucose levels.

UR - http://www.scopus.com/inward/record.url?scp=12244299450&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=12244299450&partnerID=8YFLogxK

U2 - 10.1210/jc.2004-1133

DO - 10.1210/jc.2004-1133

M3 - Article

VL - 90

SP - 493

EP - 500

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 1

ER -