Altered Glucose Homeostasis Is Associated with Increased Serum Apelin Levels in Type 2 Diabetes Mellitus

Abstract

BackgroundApelin is an adipokine that plays a role in the regulation of glucose homeostasis and in obesity. The relationship between apelin serum concentration and dysmetabolic conditions such as type 2 diabetes (T2D) is still controversial. Aims of our study are: 1) determine the circulating levels of apelin in a large cohort of Italian subjects with T2D, T1D and in non-diabetic controls; 2) identify putative metabolic determinants of modified apelin concentrations, in order to search possible mechanism of apelin control; 3) investigate changes in apelin levels in response to sharp modifications of glucose/insulin metabolism in T2D obese subjects before and 3 days after bariatric surgery.MethodsWe recruited 369 subjects, 119 with T2D, 113 with T1D and 137 non-diabetic controls. All subjects underwent a complete clinical examination, including anthropometric and laboratory measurements. Serum apelin levels were determined by EIA (immunoenzyme assay).ResultsPatients with T2D had significantly higher serum apelin levels compared to controls (1.23±1.1 ng/mL vs 0.91±0.7 ng/mL, P<0.001) and to T1D subjects (0.73±0.39 ng/mL, P<0.001). Controls and T1D subjects did not differ significantly in apelin levels. Apelin concentrations were directly associated with fasting blood glucose (FBG), body mass index (BMI), basal Disposition Index (DI-0), age, and diagnosis of T2D at bivariate correlation analysis. Multiple regression analysis confirmed that diagnosis of T2D, basal DI-0 and FBG were all determinants of serum apelin levels independently from age and BMI. Bariatric surgery performed in a subgroup of obese diabetic subjects (n = 12) resulted in a significant reduction of apelin concentrations compared to baseline levels (P = 0.01).ConclusionsOur study demonstrates that T2D, but not T1D, is associated with increased serum apelin levels compared to non-diabetic subjects. This association is dependent on impaired glucose homeostasis, and disappears after bariatric surgery, providing further evidence regarding the relationship between apelin and the regulation of glucose metabolism.

Apelin receptors: From signaling to antidiabetic strategy

“…Cavallo et al reported different results: Type 2, but not type 1 diabetic patients, had increased serum apelin concentrations compared to non-diabetic subjects. (Cavallo et al, 2012). These discrepancies for type 1 diabetes could be explained by the differences in the population studied (age, body mass index and diabetes duration).…”

The apelin receptor APJ: journey from an orphan to a multifaceted regulator of homeostasis

“…Clinical studies have shown a promising therapeutic value for apelin, as apelin displays beneficial glucose-lowering effects in human adipose tissue and plasma apelin levels correlate with glucose (Soriguer et al 2009) and HbA1c (Dray et al 2010) levels. Apelin is linked to the pathogenesis of T2D -plasma apelin concentrations are increased in insulin-resistant patients (Li et al 2006), in type T2D patients (Cavallo et al 2012) and in morbidly obese T2D individuals (Soriguer et al 2009), perhaps indicating a compensatory role of apelin in the reduction of insulin resistance. However, conversely, plasma apelin levels are reduced in newly diagnosed T2D patients (Erdem et al 2008) and increased in T2D patients and obese non-diabetic individuals (Boucher et al 2005, Dray et al 2010.…”

On the relationship between serum apelin levels and some parameters related to oxidative stress and energy metabolism in obese and non-obese

“…14 Researchers found a significant decrease in serum apelin levels after bariatric surgery in obese subjects with Type 2 diabetes in the same study group. The results from researchers' work indicate that the relationship between Type 2 diabetes and apelin is related to glucose balance, but not to obesity and other metabolic abnormalities.…”

“…Increased apelin with hyperinsulinemia was observed in obese subjects. [14][15][16] There are studies reporting that the antioxidant capacity is impaired in obesity. 17,18 Sudden or excessive oxygen entrance into the organism due to various metabolic reasons, antioxidant defense system insufficiency or oxidant-antioxidant balance to gravitate towards the oxidant side, which then leads to occurrence of oxidative stress.…”