Galectin-1 is inversely associated with type 2 diabetes independently of obesity – A SCAPIS pilot study

Abstract

Objectives Galectin-1 is a recently discovered adipokine that increases with obesity and increased energy intake in adipose tissue. Our aim was to assess whether serum galectin-1 is associated with type 2 diabetes (T2D) and other parameters of the metabolic syndrome independently of body mass index (BMI) in a cohort from the general population. Methods In this cross-sectional population-based cohort study from the western part of Sweden, we investigated associations between serum galectin-1, clinical characteristics and inflammatory markers in 989 women and men aged 50–65 years [part of the Swedish CArdioPulmonary bioImage Study (SCAPIS) pilot cohort]. Results We showed in linear models that serum galectin-1 was independently and: (1) inversely associated with T2D (p < 0.05) and glucose (p < 0.05); and (2) positively associated with age (p < 0.01), sex (p < 0.01), BMI (p < 0.01), insulin (p < 0.01) and C-reactive protein (p < 0.01). Furthermore, galectin-1 demonstrated univariate correlations with triglycerides (r = 0.20, p < 0.01), homeostasis model assessment for insulin resistance (r = 0.24, p < 0.01), tumor necrosis factor-α (r = 0.24, p < 0.01), interleukin-6 (IL-6; r = 0.20, p < 0.01) and HbA1c (r = 0.14, p < 0.01). Conclusion In a cross-sectional study of a middle-aged population, we showed that serum galectin-1 is: (1) inversely associated with T2D independently of BMI; and (2) independently associated with other markers of the metabolic syndrome These results warrant prospective and functional studies on the role of galectin-1 in T2D.

The role of circulating galectin-1 in type 2 diabetes and chronic kidney disease: evidence from cross-sectional, longitudinal and Mendelian randomisation analyses

“…The relationship between obesity, type 2 diabetes and declined renal function is well known [ 31 – 33 ], although the causal pathways are not fully established [ 34 ]. In agreement with earlier epidemiological studies, BMI and related clinical markers of the metabolic syndrome correlated with circulating galectin-1 levels in our study [ 17 , 35 ]. Conversely, we have previously reported that there is an inverse relationship between galectin-1 and type 2 diabetes when adjusting for BMI [ 17 ].…”

“…In agreement with earlier epidemiological studies, BMI and related clinical markers of the metabolic syndrome correlated with circulating galectin-1 levels in our study [ 17 , 35 ]. Conversely, we have previously reported that there is an inverse relationship between galectin-1 and type 2 diabetes when adjusting for BMI [ 17 ]. A study on pregnant women also reported that participants develop gestational diabetes when the adaptive increase of galectin-1 is impaired during pregnancy [ 36 ].…”

“…Galectin-1 was measured at baseline and analysed years after the initial sampling; however, we have tested the stability of galectin-1 in five repeated freeze–thaw cycles of biobanked samples without significant changes in galectin-1 concentration (data not shown). Furthermore, galectin-1 levels measured in this cohort were comparable with those in our recent study [ 17 ]. Another limitation is that diabetes type was not specified for 46% of the incident cases in the MDCS-CC.…”

“…Interestingly, in previous studies, we have measured higher galectin-1 levels in the subcutaneous interstitial fluid, but similar serum levels, in individuals with type 2 diabetes compared with healthy control participants [ 16 ]. We have also observed a strong cross-sectional association between circulating levels of galectin-1 and several markers of the metabolic syndrome in a population-based cohort, but BMI-adjusted galectin-1 levels were lower in individuals with type 2 diabetes [ 17 ]. However, longitudinal evidence on the association between galectin-1 and diabetes risk remains to be shown.…”

The Combined Partial Knockdown of CBS and MPST Genes Induces Inflammation, Impairs Adipocyte Function-Related Gene Expression and Disrupts Protein Persulfidation in Human Adipocytes

“…Pharmacological inhibition of LGALS1 displayed important anti-obesogenic and anti-adipogenic effects [ 48 , 49 ], strengthening the role of this protein in the development of fat mass and obesity. Otherwise, circulating galectin-1 levels were negatively associated with type 2 diabetes [ 50 , 51 ], indicating that it might be associated with healthy adiposity. PHB is induced during adipocyte differentiation, in response to insulin and PPARγ agonist, and its overexpression in 3T3-L1 fibroblasts was sufficient to induce adipogenesis [ 52 ], but its gene knockdown reduces the expression of adipogenic genes and lipid accumulation and impairs mitochondrial dysfunction [ 53 , 54 ].…”