Phenotyping of type 2 diabetes mellitus at onset on the basis of fasting incretin tone: Results of a two-step cluster analysis

Aims/IntroductionAccording to some authors, in type2 diabetes there is a reduced postprandial action of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). However, little is known about the role of fasting incretins in glucose homeostasis. Our aim was to evaluate, through a two-step cluster analysis, the possibility of phenotyping patients with type2 diabetes at onset on the basis of fasting GLP-1, GIP and ghrelin. Materials and MethodsA total of 96 patients with type2 diabetes within 6months of onset (mean age 62.406.36years) were cross-sectionally studied. Clinical, anthropometric and metabolic parameters were evaluated. At fasting the following were carried out: assay of GLP-1, GIP, ghrelin, insulin, C-peptide, glucagon and a panel of adipocytokines (visfatin, resistin, leptin, soluble leptin receptor and adiponectin). ResultsThe analysis resulted in two clusters: cluster1 (63 patients) had significantly lower levels of GLP-1 (4.93 +/- 0.98 vs 7.81 +/- 1.98pmol/L; P<0.001), GIP (12.73 +/- 9.44 vs 23.88 +/- 28.56pmol/L; P<0.001) and ghrelin (26.54 +/- 2.94 vs 39.47 +/- 9.84pmol/L; P<0.001) compared with cluster2 (33 patients). Between the two clusters, no differences in age, duration of disease, sex, clinical-anthropometric parameters, insulin sensitivity and adipocytokines were highlighted. However, cluster1 was associated with significantly higher levels of glycated hemoglobin (7.4 +/- 0.61 vs 6.68 +/- 0.57%, P=0.007), glucagon (232.02 +/- 37.27 vs 183.33 +/- 97.29ng/L; P=0.001), fasting glucose (7.85 +/- 1.60 vs 6.93 +/- 1.01mmol/L; P=0.003) and significantly lower levels of C-peptide (0.12 +/- 0.11 vs 0.20 +/- 0.20nmol/L; P=0.017). ConclusionsThe present study suggests that fasting incretins play an important role in the pathophysiology of type2 diabetes, which requires to further investigation.