Postprandial glucose profiles may reflect heterogeneity in insulin secretion and sensitivity in type 2 diabetes

A. Giosuè, V. Skantze, R. Testa, G. D’Abbronzo, G. Costabile, M. Vitale, A. Corrado, M. Jirstrand, R. Landberg, G. Riccardi, and L. Bozzetto. Metabolism, vol. 181, p. 156626, May 2026.

Abstract

BackgroundContinuous glucose monitoring (CGM) reveals heterogeneity of postprandial glucose responses (PPGR), a key target for optimizing glycemic control in type 2 diabetes (T2D). We analyzed PPGR patterns to identify subtypes reflecting pathophysiological differences.

Methods

Cross-sectional CGM data from 100 individuals with T2D were collected over 4 h following a standardized meal consumed twice. Dynamic PPGR features—glucose peak, incremental area under the curve (iAUC), rise and fall rates, final vs. fasting glucose—were used for K-Means clustering, with stability assessed using a Random Forest classifier trained on the first meal. In 50 participants, postprandial plasma glucose and insulin were measured, and clinical/metabolic parameters compared across clusters using one-way ANOVA.

Results

Three CGM-defined PPGR clusters were identified. Cluster 1 (n = 19) showed the highest peak and iAUC, with post-meal glucose remaining persistently above baseline. Cluster 2 (n = 56) and 3 (n = 25) had lower peaks and iAUCs, but Cluster 3 exhibited higher rise and fall rates than Cluster 2. Clusters did not differ in age, sex, BMI, or diabetes duration, but metformin use was lower in Cluster 3. Cluster 1 showed significantly lower insulin secretion (HOMA2-B%: 77.42 ± 25.64 vs. 104.96 ± 43.94) and higher insulin resistance (HOMA-IR: 7.94 ± 3.27 vs. 4.84 ± 2.78) than Cluster 3, with intermediate values for Cluster 2, confirmed by postprandial indices. Cluster 3 had a higher early insulin response than Cluster 1 and 2 (60-min insulinogenic index: 1.67 ± 1.07, 0.84 ± 0.31, 0.84 ± 0.58, respectively; p < 0.05).
Conclusions

CGM-derived PPGR features could identify T2D subtypes with similar clinical profiles but distinct insulin secretion and sensitivity impairments, supporting targeted interventions.




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