Glucosamine Use, Inflammation, and Genetic Susceptibility, and Incidence of Type 2 Diabetes: A Prospective Study in UK Biobank

Abstract

Glucosamine is a widely used supplement typically taken for osteoarthritis and joint pain. Emerging evidence suggests potential links of glucosamine with glucose metabolism, inflammation, and cardiometabolic risk. We prospectively analyzed the association of habitual glucosamine use with risk of type 2 diabetes (T2D) and assessed whether genetic susceptibility and inflammation status might modify the association. RESEARCH DESIGN AND METHODSThis study analyzed 404,508 participants from the UK Biobank who were free of diabetes, cancer, or cardiovascular disease at baseline and completed the questionnaire on supplement use. Cox proportional hazards models were used to evaluate the association between habitual use of glucosamine and risk of incident T2D. RESULTSDuring a median of 8.1 years of follow-up, 7,228 incident cases of T2D were documented. Glucosamine use was associated with a significantly lower risk of T2D (hazard ratio 0.83, 95% CI 0.78-0.89) after adjustment for age, sex, BMI, race, center, Townsend deprivation index, lifestyle factors, history of disease, and other supplement use. This inverse association was more pronounced in participants with a higher blood level of baseline C-reactive protein than in those with a lower level of this inflammation marker (P-interaction 5 0.02). A genetic risk score for T2D did not modify this association (P-interaction 5 0.99). CONCLUSIONSOur findings indicate that glucosamine use is associated with a lower risk of incident T2D.Glucosamine is a widely used supplement typically taken for osteoarthritis and joint pain (1). It has been estimated that ;20% of middle-aged adults use this supplement in the U.S., U.K., and Australia (2-4), although studies on the effectiveness of glucosamine on osteoarthritis have reported conflicting results (5).In a recent study, we found that habitual glucosamine use was significantly associated with lower risks of cardiovascular diseases (4). Notably, previous studies have also linked glucosamine use with glucose metabolism, although the evidence is not consistent. Several in vitro studies reported that glucosamine altered glucose

Glucosamine and O-GlcNAcylation: a novel immunometabolic therapeutic target for OA and chronic, low-grade systemic inflammation?

“…11 In turn, epidemiological data provided by several sound studies strongly suggested an association between GlcN use and lower risk of CVD, cancer and other diseases. [5][6][7][8] The current report by Li et al, involving 495 077 individuals, provides further evidence for the association between GlcN use and lower risk for all-cause mortality (15%) and causespecific mortality, including CVD (18%), cancer (6%), respiratory (27%) and digestive (26%), 6 supporting previous studies. 5 12 However, these data should be evaluated with caution, as unexpected bias in the study design could exist.…”

“…14 Furthermore, studies on type 2 diabetes (T2D) also indicate that patients on GlcN treatment showed a decrease in T2D incidence, after adjustment for different confounding factors. 8 Again, the decrease in T2D incidence was greater in patients with higher serum CRP. Overall, a relationship between the higher rate of CSI and the protective effect of GlcN intake is observed.…”

“…2 Although the efficacy of glucosamine (GlcN) in the treatment of OA is still a controversial issue 3 4 , recent high-quality epidemiological studies confirm previous data showing that prolonged GlcN intake, regardless of its effect on OA progression, could decrease cardiovascular disease (CVD) events, and the incidence of CVDassociated diseases. [5][6][7][8] These data should be analysed keeping in mind that CVD is the main cause of death in patients with OA. 9 Different authors suggest that this protective effect may be associated with the anti-inflammatory properties of GlcN, 5 although the molecular basis has been only partially defined.…”

Glucose transporters in adipose tissue, liver, and skeletal muscle in metabolic health and disease

“…On the other hand, glucosamine was shown to extend the life span of Caenorhabditis elegans and aging mice which was associated with an induction of mitochondrial biogenesis, lowered blood glucose levels, and increased amino acid catabolism, as found in the context of low-carbohydrate diets [251]. Interestingly, a recent study showed that long-term (8-year) supplementation of glucosamine is associated with a lower risk of incident type 2 diabetes in humans [137].…”

Glucosamine sulphate: an umbrella review of health outcomes

“…62 Present data, although limited by the narrative nature of the review, confirmed that GS is safe from a metabolic point of view, being in agreement with a large longitudinal study using the UK Biobank showing that the use of GS in OA is associated with a lower incidence of diabetes, over 8 years of follow up. 63 In the same database, it is reported that GS can lead to a reduction in cardiovascular disease 64 and all-cause and specific-cause mortality. 65 Further studies are encouraged in order to confirm these promising findings, since in the UK Biobank the data are reported for different glucosamine preparations and not specifically for GS.…”