Profiles of Glucose Metabolism in Different Prediabetes Phenotypes, Classified by Fasting Glycemia, 2-Hour OGTT, Glycated Hemoglobin, and 1-hour OGTT: An IMI DIRECT Study

Abstract

Differences in glucose metabolism among categories of prediabetes have not been systematically investigated. In this longitudinal study, participants (<i>N</i>=2111) underwent 2h-75g OGTT at baseline and 48 months. HbA1c was also measured. We classified participants as having isolated prediabetes defect (impaired fasting glucose, IFG; impaired glucose tolerance, IGT; HbA1c-prediabetes, IA1c), two defects (IFG+IGT, IFG+IA1c, IGT+IA1c), or all defects (IFG+IGT+IA1c). Beta-cell function (BCF) and insulin sensitivity (IS) were assessed from OGTT. At baseline, when pooling participants with isolated defects, they showed impairment in both BCF and IS compared to healthy controls. Pooled groups with two or three defects showed progressive further deterioration. Among groups with isolated defect, IGT showed lower IS, insulin secretion at reference glucose (ISR<sub>r</sub>), and insulin secretion potentiation (p<0.002). Conversely, IA1c showed higher IS and ISR<sub>r</sub> (p<0.0001). Among groups with two defects, we similarly found differences in both BCF and IS. At 48 months, we found higher type 2 diabetes incidence for progressively increasing number of prediabetes defects (odds ratio >2, p<0.008). In conclusion, the prediabetes groups showed differences in type/degree of glucometabolic impairment. Compared to the pooled group with isolated defects, those with double or triple defect showed progressive differences in diabetes incidence.

Criteria for prediabetes and posttransplant diabetes mellitus after kidney transplantation: A 2-year diagnostic accuracy study of participants from a randomized controlled trial

“…Apart from PTDM, we evaluated thresholds for increased diabetes risk using ADA criteria for prediabetes , on the basis that IGT 5 as well as IGT and/or IFG pose specific risk factors after transplantation 6 . In the general population, IGT and IFG have also been shown to be characterized by distinct metabolic characteristics 30 . HbA 1c was not added as a reference criterion for prediabetes because, to our knowledge, HbA 1c 5.7%–6.4% (39–47 mmol/mol) has not been linked to cardiovascular events after transplantation 6 and was only evaluated as an index test, in contrast to IGT and IFG.…”

“…6 In the general population, IGT and IFG have also been shown to be characterized by distinct metabolic characteristics. 30 HbA 1c was not added as a reference criterion for prediabetes because, to our knowledge, HbA 1c 5.7%-6.4% (39-47 mmol/mol) has not been linked to cardiovascular events after transplantation 6 and was only evaluated as an index test, in contrast to IGT and IFG. The diagnostic accuracy of FPG 100-125 mg/ dl (5.6-6.9 mmol/L) and HbA 1c 5.7%-6.4% (39-47 mmol/mol) 1 were therefore assessed in the absence of PTDM and compared with the OGTT-derived diagnosis of IGT and IGT and/or IFG.…”

Does the Effect of a 3-Year Lifestyle Intervention on Body Weight and Cardiometabolic Health Differ by Prediabetes Metabolic Phenotype? A Post Hoc Analysis of the PREVIEW Study

“…Very few previous studies have investigated prediabetes metabolic phenotype and cardiometabolic benefits from long-term lifestyle interventions, but some studies reported differences between individuals with IFG+IGT vs iIFG in type 2 diabetes incidence. In the Innovative Medicines Initiative Diabetes Research on Patient Stratification (IMI DIRECT) study, without intervention, diabetes incidence was higher in individuals with IFG+IGT vs iIFG (30). This pattern, however, did not change after the lifestyle intervention.…”

“…Accordingly, in diabetes and CVD prevention, individuals with prediabetic hyperglycemia but normal HbA1c should also be considered a target population and should not be ignored. Moreover, in the IMI DIRECT study, individuals with both prediabetic hyperglycemia and intermediate HbA1c, especially with intermediate HbA1c+IFG+IGT, had more severe impairments of both β-cell function and insulin sensitivity and higher risk of developing diabetes, compared with those with iIFG and iIGT (30). In the Whitehall II Study, whilst Vistisen et al (33) demonstrated that prediabetes phenotypes influenced CVD risk, the risk was primarily explained by the clustering of cardiometabolic risk factors associated with hyperglycemia (e.g.…”

“…This means that if prediabetes had been defined by using only HbA1c, more than 70% of participants would not have met the criteria for enrolment and not been eligible for the intervention. In the IMI DIRECT study, individuals with prediabetic hyperglycemia, but normal HbA1c, had higher risk of developing type 2 diabetes than those with normal glucose tolerance (30). Accordingly, in diabetes and CVD prevention, individuals with prediabetic hyperglycemia but normal HbA1c should also be considered a target population and should not be ignored.…”