Abstract
Background/aimsPrevious 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.Methods1002 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).ResultsPrevalence 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).ConclusionsOur 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.
Highlights
Prediabetes status forms an intermediate stage in the natural history of type 2 diabetes mellitus (T2DM), and behaves a high risk of cardiovascular complications
Based in this previous evidence, the aim of this study was examined the degree of postprandial lipemia response measured with the fat tolerance test according to their diabetic status: prediabetic, non-diabetic and diabetic patients from the large cohort of CORDIOPREV clinical trial (NCT00924937)
One way analysis of variance (ANOVA) BMI body mass index, HbA1c glycated hemoglobin, hsCRP high sensitivity C-reactive protein, HOMA-IR homeostatic model assessment insulin resistance, oral glucose tolerance test (OGTT) standard overload glucose tolerance test, HIRI hepatic insulin resistance index, muscle insulin sensitibity index (MISI) muscle insulin resistance index * p < 0.05 posthoc Bonferroni analysis according three subgroups according to the diabetic status in the CORDIOPREV population: 57 non diabetic, 364 prediabetic and 581 diabetic
Summary
Prediabetes status forms an intermediate stage in the natural history of type 2 diabetes mellitus (T2DM), and behaves a high risk of cardiovascular complications. The average risk of development diabetes increases 0.7 % per year in people with normal glucose levels, and 5–10 % per year in prediabetic patients [1] At this stage of the disease, it is possible to return a normal state [2]. T2DM has been associated with abnormal postprandial lipoprotein metabolism, with a significant delay in the clearance of lipoproteins, including triglycerides (TG) and chylomicrons [3] This fact could support the hypothesis to consider T2DM as a systems disease with loss of flexibility in one or more metabolic processes involved. The capacity to adapt in time and location to alterations in external factors, such as environmental conditions, is called phenotypic flexibility [4] One biomarker of this phenotypic inflexibility is the degree of postprandial triglyceride response. It is important to understand whether the underlying causes of metabolic inflexibility may influence the maintenance of overall triglycerides homoeostasis in the prediabetic status
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