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

AIMS/INTRODUCTION: According to some authors, in type 2 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 type 2 diabetes at onset on the basis of fasting GLP‐1, GIP and ghrelin. MATERIALS AND METHODS: A total of 96 patients with type 2 diabetes within 6 months of onset (mean age 62.40 ± 6.36 years) 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). RESULTS: The analysis resulted in two clusters: cluster 1 (63 patients) had significantly lower levels of GLP‐1 (4.93 ± 0.98 vs 7.81 ± 1.98 pmol/L; P < 0.001), GIP (12.73 ± 9.44 vs 23.88 ± 28.56 pmol/L; P < 0.001) and ghrelin (26.54 ± 2.94 vs 39.47 ± 9.84 pmol/L; P < 0.001) compared with cluster 2 (33 patients). Between the two clusters, no differences in age, duration of disease, sex, clinical‐anthropometric parameters, insulin sensitivity and adipocytokines were highlighted. However, cluster 1 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 ± 97.29 ng/L; P = 0.001), fasting glucose (7.85 ± 1.60 vs 6.93 ± 1.01 mmol/L; P = 0.003) and significantly lower levels of C‐peptide (0.12 ± 0.11 vs 0.20 ± 0.20 nmol/L; P = 0.017). CONCLUSIONS: The present study suggests that fasting incretins play an important role in the pathophysiology of type 2 diabetes, which requires to further investigation.