Abstract

BackgroundA novel classification has been introduced to promote precision medicine in diabetes. The current study aimed to investigate the relationship between leptin and resistin levels with novel refined subgroups in patients with type 2 diabetes mellitus (T2DM).MethodsThe k-means analysis was conducted to cluster 541 T2DM patients into the following four subgroups: mild obesity-related diabetes (MOD), severe insulin-deficient diabetes (SIDD), severe insulin-resistant diabetes (SIRD) and mild age-related diabetes (MARD). Individuals meeting the exclusion criteria were eliminated, the data for 285 patients were analyzed. Characteristics were determined using various clinical parameters. Both the leptin and resistin levels were determined using enzyme-linked immunosorbent assay.ResultsThe highest levels of plasma leptin were in the MOD group with relatively lower levels in the SIDD and SIRD groups (P < 0.001). The SIRD group had a higher resistin concentration than the MARD group (P = 0.024) while no statistical significance in resistin levels was found between the SIDD and MOD groups. Logistic regression demonstrated that plasma resistin was associated with a higher risk of diabetic nephropathy (odds ratios (OR) = 2.255, P = 0.001). According to receiver operating characteristic (ROC) curves, the area under the curve (AUC) of resistin (0.748, 95% CI 0.610–0.887) was significantly greater than that of HOMA2-IR (0.447, 95% CI 0.280–0.614) (P < 0.05) for diabetic nephropathy in the SIRD group.ConclusionsLeptin levels were different in four subgroups of T2DM and were highest in the MOD group. Resistin was elevated in the SIRD group and was closely related to diabetic nephropathy.

Highlights

  • A novel classification has been introduced to promote precision medicine in diabetes

  • The overall cluster characteristics of the five variables were described in Fig. 1 in line with Ahlqvist’s study (P values for five variables within the different subgroups (MOD, severe insulin-deficient diabetes (SIDD), severe insulin-resistant diabetes (SIRD), mild agerelated diabetes group (MARD)) < 0.001)

  • The results showed that the levels of leptin, resistin, alanine transaminase (ALT), AST, serum creatinine (SCr) and decreased glomerular filtration rate (eGFR) differed significantly among the novel subgroups (Table 1)

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Summary

Introduction

A novel classification has been introduced to promote precision medicine in diabetes. One possible reason is that type 2 diabetes mellitus (T2DM) has high heterogeneity and diabetes classification is too simple To address this issue, in 2018, Ahlqvist et al firstly defined five diabetic subgroups according to six different variables (glutamate decarboxylase antibodies (GADA), age at diagnosis, body mass index (BMI), hemoglobin A1c (HbA1c), homeostatic model assessment 2 estimates of β-cell function (HOMA2-B) and insulin resistance (HOMA2-IR)) to provide more individual and precise strategies. In Zou’s study, the diabetic patients who are GADA negative (namely T2DM patients) were stratified into four subgroups (MOD, SIDD, SIRD, MARD) using five variables (age at diagnosis, BMI, HbA1c, HOMA2-B and HOMA2-IR) using Chinese populations and obtained similar conclusions [4]. Older diabetic patients with modest metabolic disorders are defined as the MARD group [3]

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