Development and assessment of the disposition index based on the oral glucose tolerance test in subjects with different glycaemic status

Abstract

Insulin secretion and insulin sensitivity indexes are related by hyperbolic functions, allowing the calculation of the disposition index (DI) as the product of the acute insulin response (AIR) and the insulin sensitivity index (Si) from intravenous glucose tolerance test (IVGTT). Our objective was to develop an oral-DI based on the oral glucose tolerance test (OGTT) and to assess its association with glucose tolerance status. This research is structured in three studies. Study 1: OGTT were performed in 833 non-diabetic Chilean women (18-60 years) without family history of diabetes mellitus. Study 2: an independent group of n = 57 non-diabetic (18-46 years) without family history of diabetes mellitus carried out an OGTT and an abbreviated IVGTT. Study 3: a sample of 1674 Chilean adults (18-60 years) with different glycaemic status performed an OGTT. An adequate statistical fit for a rectangular hyperbola was found between the area under the curve of insulin-to-glucose ratio (AUCI/G-R) and the Matsuda ISI-COMP index (study 1). The oral-DI derived as AUCI/G-R × ISI-COMP was previously termed insulin-secretion-sensitivity index-2 (ISSI-2). ISSI-2 significantly correlated with DI from IVGTT (rho = 0.34; p = 0.009) (study 2). ISSI-2 shows important differences across groups of subjects with different glycaemic status (study 3). We have confirmed that ISSI-2 replicates the mathematical properties of DI, showing significant correlations with DI from the abbreviated MM-IVGTT. These results indicate that ISSI-2 constitutes a surrogate measure of insulin secretion relative to insulin sensitivity and emphasizes the pivotal role of impaired insulin secretion in the development of glucose homeostasis dysregulation.

Dopamine gene methylation patterns are associated with obesity markers and carbohydrate intake

“…The MENA cohort is constituted by previous clinical trials analyzing genome‐environmental interactions concerning weight management and associated metabolic outcomes (Abete et al., 2015; Huerta, Navas‐Carretero, Prieto‐Hontoria, Martínez, & Moreno‐Aliaga, 2015; Larsen et al., 2010; Martínez‐González et al., 2014; Petersen et al., 2006; San‐Cristobal et al., 2015; Santos et al., 2016; Zulet et al., 2011). Each study received ethical approval from appropriate local Human Research Ethics Committees.…”

Prediabetes and working memory in older adults

“…Total AUC ins/gluc × Matsuda index has been significantly and modestly related to the DI obtained from an IVGTT (Retnakaran et al, 2009;Santos et al, 2016). It has discriminated between NGT, impaired glucose tolerance and type 2 diabetes groups, declining from normal to diabetes, and illustrating a progressive loss of β-cell function and decreased insulin secretion in the context of increasing insulin resistance (Retnakaran et al, 2008;Santos et al, 2016). According to Kahn et al (1993), the DI is a valid measure of pancreatic β-cell function if a rectangular hyperbolic relationship between insulin secretion and insulin sensitivity can be established.…”

PPARGC1A Gene Promoter Methylation as a Biomarker of Insulin Secretion and Sensitivity in Response to Glucose Challenges

“…A group of n = 57 non-obese, non-diabetic Chilean women from the GEDYMET cohort (Genetics, Dysglycemia and Metabolism) (age: 27.4 ± 6.9 years; body mass index (BMI): 23.8 ± 3.5 kg/m 2 ) participated in this study [42]. In a first visit, biochemical and anthropometric measurements were carried out after overnight fasting, which included weight, height, blood glucose, insulin, total cholesterol, HDL cholesterol, triglycerides; and systolic and diastolic arterial pressure.…”

“…The C-peptidogenic index is equivalent to the insulinogenic index using plasma C-peptide instead of insulin measurements [44]. OGTT-based Oral Disposition Indexes (ODIs), which are surrogates of insulin secretion adjusted by systemic insulin sensitivity, were calculated as previously described [42] and as the product of the Matsuda-ISICOMP index by the C-peptidogenic index.…”