Research Article: Plasma sphingomyelins increase in pre-diabetic Korean men with abdominal obesity

Date Published: March 5, 2019

Publisher: Public Library of Science

Author(s): Seung-Soon Im, Hyeon Young Park, Jong Cheol Shon, In-Sung Chung, Ho Chan Cho, Kwang-Hyeon Liu, Dae-Kyu Song, Kyoung Heon Kim.


Abdominal or visceral obesity is a well-known risk factor for metabolic diseases. However, whether abdominal obesity significantly affects plasma lipid profile during the development of type 2 diabetes has not been fully elucidated. We investigated the differences in plasma lipid concentrations in 63 participants categorized into six groups (middle-aged Korean men); Normal, Pre-diabetes (pre-DM), and Diabetes mellitus (DM) with or without abdominal obesity (AO or lean). The lipidomic profiles were determined by using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Sphingomyelin (SM) levels in plasma were significantly higher in the pre-DM with AO than in pre-DM with lean (p = 0.021). SM concentrations correlated positively with waist-to-hip ratio (WHR) (r = 0.256, p = 0.044), cholesteryl ester (CE) (r = 0.483, p < 0.0001), ceramide (r = 0.489, p < 0.0001) and plasmanyl phosphatidylcholine (PC) (r = 0.446, p < 0.0001). The present study found that pre-diabetic patients with AO were characterized by increased plasma concentrations of SM. Plasma SM levels in individuals with AO may be an early prognostic biomarker to better predict the progression toward type 2 diabetes and metabolic syndrome.

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Obesity and type 2 diabetes are rapidly emerging as major public health problems worldwide. The rates of diabetes and obesity tended to increase in Korea [1]. Since all obese individuals are not a diabetic, the mechanism of linking obesity to diabetes is not clear yet. Indeed, Asians and Asian Americans have a lower prevalence of obesity as measured by body mass index (BMI) compared with Caucasians, but have a higher percentage of body fat at the same BMI as Caucasians [2]. In 2016, the Korean Diabetes Association reported that 58% of diabetic patients presented abdominal obesity (AO) and a quarter of the adults 30 years or older had pre-diabetes defined as impaired fasting glucose in the 100–125 mg/dL range [3]. Thus, the influence of AO on the risk of diabetes was found to be more important than that of general obesity in Asians [4]. In fact, clinical measurements of AO such as waist circumference and waist-to-hip ratio (WHR) are regarded as independent predictors for metabolic syndrome such as diabetes, hypertension, and cardiovascular diseases [5–7]. The Bangladesh study also suggested that high waist circumference and WHR reflecting AO are significant predictors of pre-diabetes [8]. Therefore, identifying AO appears to be particularly important among the Asian population at a risk of type 2 diabetes at normal BMI values [4, 9, 10]. It has been hypothesized that quantitative analysis of plasma metabolites can reveal the precise mechanisms by which or where a specific metabolic pathway is altered and deregulated in pathogenic conditions. Many studies have been conducted to identify predictive biomarkers of diabetic susceptibility. However, no biomarkers explaining the relationship between AO and progression of diabetes are yet available. Moreover, only few studies have used lipidomic analysis to characterize the relationship between AO and progression of diabetes.

According to a recent trend of type 2 diabetes in Korea, the prevalence of diabetes is increasingly shifting to obese people, and an inverse linear relationship was detected between BMI and age at diabetes diagnosis among newly diagnosed patients [1]. Nevertheless, there are many non-obese but metabolically unhealthy individuals. Previous research demonstrated that the risk of type 2 diabetes starts at a lower BMI for Asians than for Europeans [22]. Lear et al. determined that healthy Chinese and South Asian individuals present with more visceral adipose tissue than Europeans with the same BMI or waist circumference [23]. Mechanistic studies revealed that visceral adiposity is strongly associated with systemic insulin resistance, which may be one of the key pathophysiological processes in the development of diabetes [2, 24, 25]. The accumulation of visceral and omental fat tissue may induce local inflammation and release various adipocytokines, leading to systemic insulin resistance [2].




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