The cardio-metabolic protein profile is associated with development of type 2 diabetes at long term follow-up after gestational diabetes mellitus: Results from the OGFUS study

Abstract

Aims: Women with previous gestational diabetes mellitus (GDM) have an increased risk for later development of type 2 diabetes. During pregnancy, GDM affects the cardio-metabolic protein profile; however, it is unknown how GDM affects the cardio-metabolic protein profile in the long term and if it is associated with type 2 diabetes after GDM. We hypothesise that the cardio-metabolic protein profile is affected long term and is associated with the development of type 2 diabetes after GDM.

Materials and methods: A case-control follow-up study based on the Odense GDM Follow-Up Study (OGFUS) cohort, which included women with previous GDM (n = 128) and matched controls without previous GDM (n = 70). Blood samples from a follow-up assessment 8-10 years after delivery were analysed using a 29-plex panel of apolipoproteins, transport and inflammation/immune proteins using multiple-reaction-monitoring mass spectrometry.

Results: Apolipoprotein A-I, D and M were significantly lower in women with previous GDM compared to controls (all p < 0.001), while apolipoprotein L-I, H, vitamin D binding protein, CRP, vitronectin, transthyretin and complement factors 3 and B were significantly higher (p = 0.008, p < 0.001, p < 0.001, p < 0.001, p < 0.001, p = 0.005, respectively). All associations remained significant after adjustment for multiple testing except CRP, whereas apolipoprotein D, vitronectin and complement factors 3 and B were associated with the development of type 2 diabetes in women with previous GDM (p = 0.02, p = 0.001, p < 0.001, p = 0.004, respectively).

Conclusions: The cardio-metabolic protein profile 8-10 years after pregnancy is altered in women with previous GDM. Apolipoprotein D, vitronectin and complement factors 3 and B are candidate risk markers of type 2 diabetes after GDM pregnancy.

Keywords: cohort study; dyslipidaemia; gestational diabetes; insulin resistance; type 2 diabetes.

FIGURE 1

Forest plot displaying beta coefficients with 95% CI for association of cardio‐metabolic proteins to previous GDM (pGDM) and to pGDM and type 2 diabetes. Previous pregnancy with GDM (pGDM) (n = 128) compared with non‐GDM (n = 70) (blue circle). Previous GDM and type 2 diabetes development at follow‐up (n = 33) compared with non‐GDM (n = 70) (red circle). Filled circles p < 0.05; Open circles non‐significant. Lipoproteins were adjusted for HDL at follow‐up. Beta coefficients were calculated using log2 protein ratios transformed to z‐score. Apo, apolipoprotein; C3, complement factor 3; CFB, complement factor B; TTR, transthyretin; VDP, vitamin D‐binding protein; VN, vitronectin.

FIGURE 2

Correlation matrix table. (A) Transport inflammation and innate immunity proteins and markers of lipid metabolism and indices of beta‐cell function, insulin resistance and insulin sensitivity. (B) Apolipoproteins and markers of lipid metabolism and indices of beta‐cell function, insulin resistance and insulin sensitivity. Data are presented as Pearson correlation coefficient (r). HOMA‐IR: Homeostatic model assessment of insulin resistance, BIGTT‐SI: BIGTT sensitivity index, HOMA‐beta: Homeostatic model assessment of beta cell function, BIGTT‐AIR: BIGTT acute insulin response. Apo, apolipoprotein; AZGP1, zinc‐alpha‐2‐glycoprotein; C3, complement factor 3; C4b, complement factor 4b; C9, complement factor 9; CBG, corticosteroid‐binding globulin; CERU, ceruloplasmin; CFB, complement factor B; CFH, complement factor H; CRP, c‐reactive protein; Lp(a) KIV‐2 and Lp(a) KIV‐peptidase S1, variants of apo(a); RBP‐4, retinol‐binding protein 4; TFE, serotransferrin (transferrin); TTR, transthyretin; VDP, vitamin D‐binding protein; VN, vitronectin.