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Objective: To i) compare incretin responses to oral glucose and mixed meal of diabetic patients with the normoglycaemic population and ii) to investigate whether incretin responses are associated with hypertriglyceridaemia and alanine aminotransferase (ALT) as liver fat marker., Design: A population-based study., Methods: A total of 163 persons with normal glucose metabolism (NGM), 20 with intermediate hyperglycaemia and 20 with type 2 diabetes aged 40-65 years participated. Participants received a mixed meal and oral glucose load on separate occasions. Glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP) and glucagon profiles were analysed as total area under the curve (tAUC) and incremental area under the curve., Results: In diabetic patients compared with persons with NGM, we found increased GLP-1 secretion (tAUC per hour) following oral glucose (23.2 pmol/l (95% CI 17.7-28.7) vs 18.0 (95% CI 16.9-19.1), P<0.05) but not after the mixed meal. GIP secretion among diabetic patients was increased on both occasions (82.9 pmol/l (55.9-109.8) vs 47.1 (43.8-50.4) for oral glucose and 130.6 (92.5-168.7) vs 83.2 (77.5-88.9) for mixed meal, both P<0.05). After oral glucose, GLP-1 (tAUC per hour) was inversely related to fasting triglycerides. GIP (tAUC per hour) was positively related to fasting and postprandial triglycerides. Higher fasting GIP levels were related to higher fasting and postprandial triglyceride levels and ALT., Conclusion: This study confirms that in type 2 diabetes, GLP-1 secretion is generally preserved and that GIP secretion is exaggerated. The mechanism underlying the divergent associations of GLP-1 and GIP metabolism with fat metabolism and liver fat accumulation warrants further study.

Aims: To investigate the associations of HbA1c, fasting glucose, and postload plasma glucose with 10-year fatal and non-fatal cardiovascular disease (CVD) and all-cause mortality in Caucasian individuals between 50 and 75 years of age without diabetes., Method and Results: The 10-year risk of all-cause mortality and CVD in relation to HbA1cand glucose levels was assessed with Cox survival analysis in 1674 non-diabetic individuals of a population-based cohort (Hoorn Study). Analyses were stratified according to sex and adjustments were made for age and known CVD risk factors. After full adjustment, HbA1c levels ≥ 6.0% were significantly associated with an increased risk of non-fatal CVD compared with the lowest category of HbA1c (≤ 5.1%) in women [hazards ratio (HR) 2.27 (1.24-4.14)]. In addition, HbA1c as a continuous variable was significantly related to non-fatal CVD in both men [HR 1.40 (1.01-1.95)] and women [HR 2.41 (1.51-3.83)]. The relationships of HbA1 c with fatal CVD and all-cause mortality were explained by traditional CVD risk factors in both the sexes, along with the associations between fasting or postload plasma glucose and any of the outcome measures., Conclusion: In Caucasian men and especially in women between 50 and 75 years of age who are without diabetes, high HbA1c levels are associated with increased risk of future non-fatal CVD, independent of other CVD risk factors.