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.

Visceral adiposity index (VAI) is predictive of an altered adipokine profile in patients with type 2 diabetes.

AIMS: Although there is still no clear definition of "adipose tissue dysfunction" or ATD, the identification of a clinical marker of altered fat distribution and function may provide the needed tools for early identification of a condition of cardiometabolic risk. Our aim was to evaluate the correlations among various anthropometric indices [BMI, Waist Circumference (WC), Hip Circumference (HC), Waist/Hip ratio (WHR), Body Adiposity Index (BAI) and Visceral adiposity Index (VAI)] and several adipocytokines [Visfatin, Resistin, Leptin, Soluble leptin receptors (sOB-R), Adiponectin, Ghrelin, Adipsin, PAI-1, vascular endothelial growth factor (VEGF), Hepatocyte growth factor (HGF) TNF-α, hs-CRP, IL-6, IL-18] in patients with type 2 diabetes (DM2). MATERIALS AND METHODS: Ninety-one DM2 patients (age: 65.25 ± 6.38 years; 42 men and 49 women) in stable treatment for the last six months with metformin in monotherapy (1.5-2 g/day) were cross-sectionally studied. Clinical, anthropometric, and metabolic parameters were evaluated. Serum adipocytokine levels were assayed with Luminex based kits. RESULTS: At the Pearson's correlation, among all the indices investigated, VAI showed a significant correlation with almost all adipocytokines analyzed [Visfatin, Resistin and hsCRP (all p<0.001); Adiponectin, sOb-R, IL-6, IL-18, HGF (all p<0.010); Ghrelin and VEGF (both p<0.05)]. Through a two-step cluster analysis, 55 patients were identified with the most altered adipocytokine profile (patients with ATD). At a ROC analysis, VAI showed the highest C-statistic [0.767 (95% CI 0.66-0.84)] of all the indices. CONCLUSIONS: Our study suggests that the VAI, among the most common indexes of adiposity assessment, shows the best correlation with the best known adipocytokines and cardiometabolic risk serum markers. Although to date we are still far from clearly identifying an ATD, the VAI would be an easy tool for clearly mirroring a condition of cardiometabolic risk, in the absence of an overt metabolic syndrome.