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

Leon-Acuña A, Alcala-Diaz JF, Delgado-Lista J, Torres-Peña JD, Lopez-Moreno J, Camargo A, Garcia-Rios A, Marin C, Gomez-Delgado F, Caballero J, Van-Ommen B, Malagon MM, Perez-Martinez P, Lopez-Miranda J - Cardiovasc Diabetol (2016)

Bottom Line: 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).Our findings demonstrate that prediabetic patients show a lower phenotypic flexibility after external aggression, such as OFTT compared with nondiabetic patients.

View Article: PubMed Central - PubMed

Affiliation: Lipid and Atherosclerosis Unit, IMIBIC/Reina Sofia University Hospital/University of Cordoba, Cordoba, Spain.

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.

No MeSH data available.


Related in: MedlinePlus

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)
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Fig4: 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)

Mentions: Furthermore, the dynamic response was evaluated in non-diabetic patients and in diabetic patients without pharmacological treatment according to the different groups of baseline insulin resistance: liver-IR, muscle-IR, liver and muscle-IR, non-liver and non-muscle-IR. 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). No differences were observed according to the magnitude of postprandial response in group of patients with liver-IR group compared with those patients with liver-IR and muscle-IR (p > 0.05) (Fig. 3). Pearson’s correlation and linear regression were used to associate postprandial response of TG and insulin resistance indices variables: HIRI and MISI. Multiple regression analysis using the AUC-TG as dependent variable showed a significant association with HIRI (R: 0.309; CI 95 % (15327.162–24080.365); p < 0001). It has not been observed association between postprandial response and muscle-IR index. (p > 0.05) (Fig. 4a, b). Similar results were obtained using iAUC-TG as dependent variable. The analysis showed a significant association with HIRI (R: 0.2; IC 95 %: (4437.52–9238.68); p < 0.001). No significant association was observed between postprandial response and MIRI index (R: −0.012; IC 95 %: (−2047.05 to 1439.18); p = 0.732) (Fig. 4c). Finally, we explored the influence of pharmacological treatments (antihypertensives, statins, other hypolipidemic drugs, antiplaquelet, and antidiabetic drugs) on the magnitude of postprandial response and the results did not change.Fig. 3


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

Leon-Acuña A, Alcala-Diaz JF, Delgado-Lista J, Torres-Peña JD, Lopez-Moreno J, Camargo A, Garcia-Rios A, Marin C, Gomez-Delgado F, Caballero J, Van-Ommen B, Malagon MM, Perez-Martinez P, Lopez-Miranda J - Cardiovasc Diabetol (2016)

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)
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4837552&req=5

Fig4: 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)
Mentions: Furthermore, the dynamic response was evaluated in non-diabetic patients and in diabetic patients without pharmacological treatment according to the different groups of baseline insulin resistance: liver-IR, muscle-IR, liver and muscle-IR, non-liver and non-muscle-IR. 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). No differences were observed according to the magnitude of postprandial response in group of patients with liver-IR group compared with those patients with liver-IR and muscle-IR (p > 0.05) (Fig. 3). Pearson’s correlation and linear regression were used to associate postprandial response of TG and insulin resistance indices variables: HIRI and MISI. Multiple regression analysis using the AUC-TG as dependent variable showed a significant association with HIRI (R: 0.309; CI 95 % (15327.162–24080.365); p < 0001). It has not been observed association between postprandial response and muscle-IR index. (p > 0.05) (Fig. 4a, b). Similar results were obtained using iAUC-TG as dependent variable. The analysis showed a significant association with HIRI (R: 0.2; IC 95 %: (4437.52–9238.68); p < 0.001). No significant association was observed between postprandial response and MIRI index (R: −0.012; IC 95 %: (−2047.05 to 1439.18); p = 0.732) (Fig. 4c). Finally, we explored the influence of pharmacological treatments (antihypertensives, statins, other hypolipidemic drugs, antiplaquelet, and antidiabetic drugs) on the magnitude of postprandial response and the results did not change.Fig. 3

Bottom Line: 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).Our findings demonstrate that prediabetic patients show a lower phenotypic flexibility after external aggression, such as OFTT compared with nondiabetic patients.

View Article: PubMed Central - PubMed

Affiliation: Lipid and Atherosclerosis Unit, IMIBIC/Reina Sofia University Hospital/University of Cordoba, Cordoba, Spain.

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.

No MeSH data available.


Related in: MedlinePlus