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Tura, A.* ; Grespan, E.* ; Göbl, C.S.* ; Koivula, R.W.* ; Franks, P.W.* ; Pearson, E.R.* ; Walker, M.* ; Forgie, I.M.* ; Giordano, G.N.* ; Pavo, I.* ; Ruetten, H.* ; Dermitzakis, E.T.* ; McCarthy, M.I.* ; Pedersen, O.* ; Schwenk, J.M.* ; Adamski, J. ; De Masi, F.* ; Tsirigos, K.D.* ; Brunak, S.* ; Viñuela, A.* ; Mahajan, A.* ; McDonald, T.J.* ; Kokkola, T.* ; Vangipurapu, J.* ; Cederberg, H.* ; Laakso, M.* ; Rutters, F.* ; Elders, P.J.M.* ; Koopman, A.D.M.* ; Beulens, J.W.* ; Ridderstråle, M.* ; Hansen, T.H.* ; Allin, K.H.* ; Hansen, T.* ; Vestergaard, H.* ; Mari, A.* ; IMI DIRECT Consortium (Grallert, H. ; Sharma, S. ; Thorand, B.)

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.

Diabetes 70, 2092-2106 (2021)

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Differences in glucose metabolism among categories of prediabetes have not been systematically investigated. In this longitudinal study, participants (N=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_r), and insulin secretion potentiation (p<0.002). Conversely, IA1c showed higher IS and ISR_r (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.

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