Mecanismos de formacion de trombos

European Journal of Endocrinology (2008) 158 35–46

ISSN 0804-4643

CLINICAL STUDY

Impact of metformin versus the prandial insulin secretagogue, repaglinide, on fasting and postprandial glucose and lipid responses in non-obese patients with type 2 diabetes
Søren S Lund1, Lise Tarnow1, Merete Frandsen1, Ulla M Smidt1, Oluf Pedersen1,2, Hans-Henrik Parving2,3 and Allan A Vaag1,4
1 StenoDiabetes Center, Niels Steensens Vej 2, 2820 Gentofte, Denmark, 2Faculty of Health Sciences, University of Aarhus, Aarhus, Denmark, 3Department of Medical Endocrinology, Rigshospitalet, University of Copenhagen, 2100 Copenhagen, Denmark and 4Department of Endocrinology, University of Lund, S-20502 Malmo, Sweden ¨

(Correspondence should be addressed to S S Lund; Email: sqrl@steno.dk)

AbstractObjective: Non-obese patients with type 2 diabetes (T2DM) are characterized by predominant defective insulin secretion. However, in non-obese T2DM patients, metformin, targeting insulin resistance, is noninferior to the prandial insulin secretagogue, repaglinide, controlling overall glycaemia (HbA1c). Whether the same apply for postprandial glucose and lipid metabolism is unknown. Here, wecompared the effect of metformin versus repaglinide on postprandial metabolism in non-obese T2DM patients. Design: Single-centre, double-masked, double-dummy, crossover study during 2!4 months involving 96 non-obese (body mass index%27 kg/m2) insulin-naıve T2DM patients. At enrolment, patients stopped ¨ prior oral hypoglycaemic agents therapies and after a 1-month run-in period on diet-only treatment,patients were randomized to repaglinide (2 mg) thrice daily followed by metformin (1 g) twice daily or vice versa each during 4 months with 1-month washout between interventions. Methods: Postprandial metabolism was evaluated by a standard test meal (3515 kJ; 54% fat, 13% protein and 33% carbohydrate) with blood sampling 0–6 h postprandially. Results: Fasting levels and total area under the curve(AUC) for plasma glucose, triglycerides and free fatty acids (FFA) changed equally between treatments. In contrast, fasting levels and AUC of total cholesterol, low-density lipoprotein (LDL) cholesterol, non-high-density lipoprotein (non-HDL) cholesterol and serum insulin were lower during metformin than repaglinide (mean (95% confidence intervals), LDL cholesterol difference metformin versusrepaglinide: AUC: K0.17 mmol/l (K0.26; K0.08)). AUC differences remained significant after adjusting for fasting levels. Conclusions: In non-obese T2DM patients, metformin reduced postprandial levels of glycaemia, triglycerides and FFA similarly compared to the prandial insulin secretagogue, repaglinide. Furthermore, metformin reduced fasting and postprandial cholesterolaemia and insulinaemia comparedwith repaglinide. These data support prescription of metformin as the preferred drug in non-obese patients with T2DM targeting fasting and postprandial glucose and lipid metabolism. European Journal of Endocrinology 158 35–46

Introduction
Individuals with diabetes experience an excess risk of cardiovascular disease (CVD), which is not fully explained by conventional risk factors including fastingdyslipidaemia (1, 2). In individuals with and without diabetes, non-fasting abnormalities in glucose and lipid metabolism have been proposed as independent risk markers for CVD (3–5). In the postprandial state, patients with type 2 diabetes (T2DM) are characterized by more pronounced elevations in levels of glucose, insulin and triglycerides than those seen in nondiabetic individuals (6–9). Inindividuals with and without T2DM, levels of low-density lipoprotein (LDL) cholesterol have been demonstrated to decrease in the postprandial state (10, 11), and it has been suggested that LDL particles
q 2008 Society of the European Journal of Endocrinology

have an increased atherogenic potential in the postprandial compared with the fasting state (12). Moreover, levels of glycaemia,...