Figure 1.
Identification of four distinct metabolic responses.
(A) Glucose concentration during the oral glucose tolerance test (OGTT) across the four cluster groups (B) Insulin concentration during an OGTT across the four cluster groups (C) C-peptide concentration during an OGTT across the four cluster groups. (D) NEFA concentration during an OGTT across the four cluster groups. Cluster 1 is represented by a black line and ♦ marker. Cluster 2 is represented by black dashed line and ■ marker. Cluster 3 is represented by a grey dashed line and grey ▲ marker. Cluster 4 is represented by a grey line and a grey ■ marker. All values are mean ± SEM. The AUC was significantly different across the 4 cluster for glucose (p= 1.6 x 10-16), insulin (p= 1.5 x 10-3) and C-peptide (p= 2.6 x 10-6).
Figure 2.
Differential responses to an OLTT.
(A) Glucose concentration during the OLTT test across the four cluster groups (B) Insulin concentration during the OLTT across the four cluster groups (C) C-peptide concentration during the OLTT across the four cluster groups. (D) Triacylglycerol concentration during the OLTT across the four cluster groups. (E) NEFA concentration during oral lipid tolerance test across the four cluster groups. Cluster 1 is represented by a black line and ♦ marker. Cluster 2 is represented by black dashed line and ■ marker. Cluster 3 is represented by a grey dashed line and ▲ marker. Cluster 4 is represented by a grey line and a ■ marker. All values are mean ± SEM. The AUC was significantly different across the 4 cluster for glucose (p= 7.1 x 10-4), insulin (p= 1.7 x 10-3), C-peptide (p= 2.3 x 10-5), triacylglycerols (p= 9.4 x 10-4), and NEFA (p= 1.7 x 10-4).
Figure 3.
Insulin resistance and β-cell function across the four metabotypes.
(A) Insulin resistance determined by the HOMA-IR (B) β-cell function quantified as ∆I30/∆G30 (C) (∆I30/∆G30)/HOMA-IR and (D) Disposition Index determined as (∆I30/∆G30) x 1/ fasting insulin from an OGTT in 116 individuals. Cluster 1- White bar (n=17), Cluster 2 – Dark grey bar (n =34), Cluster 3 – Black bar (n = 20) and Cluster 4 – Light grey bar (n =45). As glucose tolerance declined, insulin resistance increased and β-cell function deteriorated. HOMA-IR for cluster 1 was significantly different to cluster 2 (p<0.001), cluster 3 (p<0.001) and cluster 4 (p<0.001). Cluster 1 β-cell function quantified as ∆I30/∆G30 was significantly different to cluster 2 (p<0.05) and Cluster 1 β-cell function normalised to HOMA-IR quantified as (∆I30/∆G30)/HOMA-IR was significantly different to cluster 2 (p<0.05). HOMA-IR was calculated as follows: Fasting insulin pmol/l x fasting glucose mmol/L)/ 22.5.