Hepatic insulin resistance both in prediabetic and diabetic patients determines postprandial lipoprotein metabolism: from the CORDIOPREV study

Abstract

Background/aims: Previous evidences have shown the presence of a prolonged and exaggerated postprandial response in type 2 diabetes mellitus (T2DM) and its relation with an increase of cardiovascular risk. However, the response in prediabetes population has not been established. The objective was to analyze the degree of postprandial lipemia response in the CORDIOPREV clinical trial (NCT00924937) according to the diabetic status.

Methods: 1002 patients were submitted to an oral fat load test meal (OFTT) with 0.7 g fat/kg body weight [12 % saturated fatty acids (SFA), 10 % polyunsaturated fatty acids (PUFA), 43 % monounsaturated fatty acids (MUFA), 10 % protein and 25 % carbohydrates]. Serial blood test analyzing lipid fractions were drawn at 0, 1, 2, 3 and 4 h during postprandial state. Postprandial triglycerides (TG) concentration at any point >2.5 mmol/L (220 mg/dL) has been established as undesirable response. We explored the dynamic response in 57 non-diabetic, 364 prediabetic and 581 type 2 diabetic patients. Additionally, the postprandial response was evaluated according to basal insulin resistance subgroups in patients non-diabetic and diabetic without pharmacological treatment (N = 642).

Results: Prevalence of undesirable postprandial TG was 35 % in non-diabetic, 48 % in prediabetic and 59 % in diabetic subgroup, respectively (p < 0.001). Interestingly, prediabetic patients displayed higher plasma TG and large triacylglycerol-rich lipoproteins (TRLs-TG) postprandial response compared with those non-diabetic patients (p < 0.001 and p = 0.003 respectively). Moreover, the area under the curve (AUC) of TG and AUC of TRLs-TG was greater in the prediabetic group compared with non-diabetic patients (p < 0.001 and p < 0.005 respectively). Patients with liver insulin resistance (liver-IR) showed higher postprandial response of TG compared with those patients with muscle-IR or without any insulin-resistance respectively (p < 0.001).

Conclusions: Our findings demonstrate that prediabetic patients show a lower phenotypic flexibility after external aggression, such as OFTT compared with nondiabetic patients. The postprandial response increases progressively according to non-diabetic, prediabetic and type 2 diabetic state and it is higher in patients with liver insulin-resistance. To identify this subgroup of patients is important to treat more intensively in order to avoid future cardiometabolic complications.

Keywords: CORDIOPREV study; Insulin resistance; Phenotypic flexibility; Postprandial lipemia; Prediabetic; Triglycerides.

Figures

Fig. 1

Prevalence of undesirable postprandial triglycerides (TG) in the CORDIOPREV population according to diabetic status: non-diabetic, prediabetic and diabetic subgroups. The black bars represent the percentage of patients with postprandial TG concentration at any point >220 mg/dL within each group

Fig. 2

Evolution of (a) triglycerides (TG) and (b) large triacylglycerol-rich lipoproteins (TRLs)-TG after the oral fat tolerance test, according to the presence of prediabetes, non-diabetes or diabetes state. Results are plotted as mean ± SD. Variables were compared using repeated measured ANOVA, with age, gender and BMI as covariates

Fig. 3

Evolution of triglycerides (TG) after the oral fat tolerance test according to the different basal insulin-resistance groups: muscle-IR and liver-IR, non muscle-IR and non liver-IR, liver-IR and muscle-IR. Results are plotted as mean ± SD. Variables were compared using repeated measured ANOVA, with age, gender and BMI as covariates

Fig. 4

Dispersion diagram and regression line according to AUC-TG and logarithm of HIRI (a) and MISI (b). Dispersion diagram and regression line according to iAUC-TG and logarithm of HIRI (c)