Shape of the OGTT glucose curve and risk of impaired glucose metabolism in the EGIR-RISC cohort

doi:10.1016/j.metabol.2017.02.007

Metabolism

Volume 70, May 2017, Pages 42-50

https://doi.org/10.1016/j.metabol.2017.02.007 Get rights and content

Abstract

Objective

To study whether the shape of the oral glucose tolerance test (OGTT)-glucose curve is a stable trait over time; it is associated with differences in insulin sensitivity, ß-cell function and risk of impaired fasting glucose (IFG) and glucose tolerance (IGT) in the Relationship between Insulin Sensitivity and Cardiovascular Disease (RISC) cohort.

Methods

OGTT-glucose curve shape was classified as monophasic, biphasic, triphasic and anomalous in 915 individuals. Oral glucose insulin sensitivity (OGIS), Matsuda insulin sensitivity index (ISI) and ß-cell function were assessed at baseline and 3 years apart.

Results

The OGTT-glucose curve had the same baseline shape after 3 years in 540 people (59%; κ = 0.115; p < 0.0001). Seventy percent of the participants presented with monophasic OGTT-glucose curve shape at baseline and after 3 years (percent positive agreement 0.74). Baseline monophasic shape was associated with significant increased risk of IFG (OR 1.514; 95% CI 1.084–2.116; p = 0.015); biphasic shape with reduced risk of IGT (OR 0.539; 95% CI 0.310–0.936) and triphasic shape with reduced risk of IFG (OR 0.493; 95% CI 0.228–1.066; P = 0.043) after 3 years. Increased risks of IFG (OR 1.509; 95% CI 1.008–2.260; p = 0.05) and IGT (OR 1.947; 95% CI 1.085–3.494; p = 0.02) were found in people who kept stable monophasic morphology over time and in switchers from biphasic to monophasic shape (OR of IGT = 3.085; 95% CI 1.377–6.912; p = 0.001).

Conclusion

After 3 years follow-up, the OGTT-glucose shape was stable in 59% of the RISC cohort. Shapes were associated with different OGIS and ß-cell function; persistence over time of the monophasic shape and switch from biphasic to monophasic shape with increased risk of impaired glucose metabolism.

Introduction

The oral glucose tolerance test (OGTT) is diagnostic for impaired glucose tolerance (IGT) or type 2 diabetes (T2D) [1]. The OGTT is also informative of insulin sensitivity and ß-cell function estimated by mathematical models that have produced indexes [2], [3], [4], [5], [6]. Recent studies have pointed out that the shape of the glucose curve during the OGTT reveals the risk of developing IGT [7], [8], being associated with differences in insulin sensitivity and secretion in youth [8], [9]. The peak and decay of plasma glucose during the OGTT reflect the interplay among different factors, such as the rate of intestinal glucose absorption, insulin sensitivity, ß-cell function and its components (namely ß-cell glucose sensitivity, ß-cell rate insulin sensitivity and potentiation factor), as well as the release of several gut hormones. By using robust methodology, a study of obese adolescents found that the shape of the glucose response curve during an OGTT, monophasic versus biphasic, identifies physiologically distinct groups of individuals with differences in insulin secretion and sensitivity [8]. The researchers found that the monophasic group had significantly higher glucose, insulin, c-peptide and free fatty acid OGTT areas under the curve compared with the biphasic group, with no differences in levels of glucagon, total glucagon-like peptide 1, glucose-dependent insulinotropic polypeptide and pancreatic polypeptide. Furthermore, the monophasic group had significantly lower in vivo hepatic and peripheral insulin sensitivity, lack of compensatory first and second phase insulin secretion, and impaired ß-cell function relative to insulin sensitivity that may pose them at increased risk of developing T2D [8]. Most of the previous studies [9], [10], [11], [12] did not demonstrate whether the OGTT-glucose curve shape is longitudinally associated with increased risk of T2D. Abdul-Ghani et al. [12], on the contrary, found that the risk of incident T2D was double in people with monophasic shape respect to the risk of people with biphasic shape over 8 years of follow-up. None of these studies investigated whether the shape of the glucose curve is a stable individual's trait that persists over years.

In the present study, we analyzed longitudinal data from the Relationship between Insulin Sensitivity and Cardiovascular Disease (RISC) Study [13]. The RISC Study had the ideal study design to answer these questions. Insulin sensitivity was estimated using the euglycemic hyperinsulinemic clamp (EHC) at baseline; the Matsuda's insulin sensitivity index [2] (ISI) and the oral glucose insulin sensitivity (OGIS) [3] at baseline and 3 years apart. ß-cell function was estimated using the Mari's model [5], [6].

Section snippets

Research Design and Methods

The RISC study is a prospective, 3-year, observational cohort study. Its primary objective was to test whether insulin resistance (IR) predicts the deterioration of atherosclerosis, as measured by the intima media thickness of the carotid arteries, as well as the deterioration of cardiovascular risk markers, diabetes, obesity, and cardiovascular disease. Secondary aim was to develop mathematical models to identify people with IR in clinical practice.

The RISC cohort included adults, aged 30–60

Description of the Sample

Table 1 shows anthropometric and laboratory data of participants at baseline and follow-up. Insulin sensitivity as measured by the EHC was correlated with OGIS and ISI (r_Sp = 0.539 and 0.560, respectively; p < 0.0001 for both). At baseline, neodiagnosis of IGT was done in some participants and some anthropometric and metabolic parameters deteriorated over-time in the cohort as a whole. Prevalence of IFG increased from 15% to 27.3% and IGT from 9% to 12.7% (IGT group at follow-up included 5 cases of

Discussion

The monophasic glucose curve was the most frequent shape occurring in about 70% of the participants. It was associated with increased risk of developing impaired glucose metabolism after 3 years in people who retained stable the shape over time and in those who switched the shape from the monophasic one. In keeping with Kim et al. [8], we found that people with monophasic shape have the lowest OGTT derived indexes of insulin sensitivity, the highest value of plasma glucose at 1 h and under the

Author Contributions

All authors have approved the final version of the manuscript; MM drafted the manuscript and all the authors critically revised it; MM conceived the design of the study and interpreted results; GN analyzed data; Z.P., L.M., F.P. G.R., A.M. G.M. acquired data.

Funding

The RISC Study was supported by EU grant QLG1-CT-2001-01252 additional support has been provided by AstraZeneca (Sweden).

The EGIR group activities are supported by an unrestricted research grant from Merck Serono, France.

Disclosure

Authors have no conflict of interest to disclose.

Acknowledgment

RISC recruiting centers and investigators.

Amsterdam, the Netherlands: R.J. Heine, J. Dekker, S. de Rooij, G. Nijpels, and W. Boorsma. Athens, Greece: A. Mitrakou, S. Tournis, K. Kyriakopoulou, and P. Thomakos. Belgrade, Serbia: N. Lalic, K. Lalic, A. Jotic, L. Lukic, and M. Civcic. Dublin, Ireland: J. Nolan, T.P. Yeow, M. Murphy, C. DeLong, G. Neary, M.P. Colgan, and M. Hatunic. Frankfurt, Germany: T. konrad, H. Böhles, S. Fuellert, F. Baer, and H. Zuchhold. Geneva, Switzerland: A. Golay, E.

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Clinical ScienceShape of the OGTT glucose curve and risk of impaired glucose metabolism in the EGIR-RISC cohort

Abstract

Objective

Methods

Results

Conclusion

Introduction

Section snippets

Research Design and Methods

Description of the Sample

Discussion

Author Contributions

Funding

Disclosure

Acknowledgment

Metab Clin Exp

Expert committee on the diagnosis and classification of diabetes mellitus report of the American Diabetes Association

Diabetes Care

Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp

Diabetes Care

A model-based method for assessing insulin sensitivity from the oral glucose tolerance test

Diabetes Care

Use of the oral glucose tolerance test to assess insulin release and insulin sensitivity

Diabetes Care

Meal and oral glucose tests for assessment of β-cell function: modeling analysis in normal participants

Am J Physiol Endocrinol Metab

Assessing insulin secretion by modeling in multiple-meal tests: role of potentiation

Diabetes

The shape of plasma glucose concentration curve during OGTT predicts future risk of type 2 diabetes

Diabetes Metab Res Rev

The shape of the glucose response curve during an oral glucose tolerance test heralds biomarkers of type 2 diabetes risk in obese youth

Diabetes Care

Clinical Science
Shape of the OGTT glucose curve and risk of impaired glucose metabolism in the EGIR-RISC cohort