Significant inverse association between serum osteocalcin and incident type 2 diabetes in a middle‐aged cohort

Hua, Shucheng; Pei, Yu; Chen, Kang; Lu, Juming

doi:10.1002/dmrr.2808

Cited by 19 publications

(18 citation statements)

References 34 publications

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“…These findings are in accordance with previous results showing that N-MID was protective against T2DM by improving insulin sensitivity and secretion. Furthermore, the same role of osteocalcin in glucose metabolism was also demonstrated in previous population studies [19,26,27] . Therefore, osteocalcin is a critical molecule that favorably modulates glucose homeostasis.…”

Section: Discussionsupporting

confidence: 81%

“…Furthermore, the intermittent infusion of osteocalcin was shown to partially correct the glucose intolerance caused by a high-fat diet in mice [15] . Although animal studies have provided evidence supporting a key role for bone in energy metabolism via osteocalcin, the association between osteocalcin and glucose metabolism remains controversial based on previous observational studies in humans [16][17][18][19] .…”

Section: Introductionmentioning

confidence: 99%

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Association of bone turnover markers with glucose metabolism in Chinese population

et al. 2017

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The association between type 2 diabetes (T2DM) and bone metabolism has been discussed previously but is controversial. In this study we aimed to evaluate the association of bone turnover markers with glucose metabolism in Chinese population, in which 919 males and 4171 postmenopausal females in a region of Shanghai were recruited. Anthropometric and biochemical traits related to glucose and bone metabolism were analyzed. Participants were classified according to their glucose tolerance as normal glucose tolerance (NGT), impaired glucose regulation (IGR) or T2DM. Males and females were analyzed separately, and then associations between bone turnover markers (BTMs) and glucose metabolism were evaluated. The results showed that in females, the serum levels of N-terminal osteocalcin (N-MID), N-terminal procollagen of type I collagen (PINP) and β-cross-linked C-telopeptide of type I collagen (β-CTX) were significantly decreased in the T2DM group compared to the NGT group (P<0.01). When age, body mass index, serum lipids, fat percentage, visceral fat area, subcutaneous fat area, anti-diabetic medicines, PINP, N-MID and β-CTX were included in one logistic model, N-MID (OR [95% CI]: 0.954 [0.932; 0.976]; P=0.0001) was significantly associated with T2DM in females. In females, N-MID was associated with insulin sensitivity and HOMA-β. PINP was significantly associated with HOMA-β, GUTT-ISI, Stumvoll first-phase insulin secretion index (STU-1) and Stumvoll second-phase insulin secretion index (STU-2), but β-CTX was associated only with HOMA-β (β±SE: 0.1331±0.0311; P=1.95×10) and GUTT-ISI (β±SE: 0.0727±0.0229; P=0.0015). In males, N-MID was significantly correlated with HOMA-β (β±SE: 0.3439±0.0633; P=7.75×10), GUTT-ISI (β±SE: 0.1601±0.0531; P=0.0027) and STU-1 (β±SE: 0.2529±0.1033; P=0.0146). Significant associations were also detected between β-CTX and HOMA-β (β±SE: 0.2736±0.0812; P=0.0009). This study reveals that BTMs are highly associated with T2DM, insulin sensitivity and beta cell function in both Chinese males and postmenopausal females.

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Section: Discussionsupporting

confidence: 81%

Section: Introductionmentioning

confidence: 99%

Association of bone turnover markers with glucose metabolism in Chinese population

et al. 2017

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“…In a large cross-sectional analysis of older men aged 70 to 89 years residing in the community of Perth, Western Australia, higher ucOC was found inversely associated with reduced diabetic risk [25]. Shu et al found OC at baseline was negatively related to the risk of incident T2DM during a 3-year follow-up [26]. In addition, maternal oral administration of ucOC during gestation protected high-fat, high-sucrose diet-fed female offspring from metabolic disorders induced by maternal obesity [27].…”

Section: Discussionmentioning

confidence: 99%

Association between serum osteocalcin and glucose/lipid metabolism in Chinese Han and Uygur populations with type 2 diabetes mellitus in Xinjiang: two cross-sectional studies

Chen

Zhao

et al. 2017

Lipids Health Dis

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BackgroundRecent studies have shown osteocalcin (OC) plays an important role in regulating glucose and lipid metabolism. Thus, the aim of this study was to investigate the association of OC with glucose and lipid metabolism in patients with type 2 diabetes mellitus (T2DM) in the Chinese Han and Uygur population.MethodsA total of 1397 T2DM patients (705 Han and 692 Uygur T2DM patients) were enrolled in the present study. Lipid profile, glucose metabolic indices and total OC (TOC) were measured. Homeostasis model assessment of β-cells function (HOMA-β), insulin sensitivity (HOMA-IS) and insulin resistance (HOMA-IR) were also calculated in all participants. Pearson/Spearman correlation analysis and multivariate stepwise regression analysis were adopted to test the relationships between OC and those parameters.ResultsUygur T2DM patients had significantly higher body mass index (BMI), hemoglobin A1C (HbA1C) and lower TOC compared with their Han counterparts (all P < 0.05). HbA1C was negatively associated with TOC in all Uygur and Han T2DM patients (Total: Uygur: t = −3.468, P = 0.001; Han: t = −4.169, P < 0.001). BMI was inversely associated with TOC in all Uygur T2DM patients (Males: t = −2.893, P = 0.014; Females: t = −2.250, P = 0.027, respectively). Multivariate stepwise regression analysis showed that TOC was positively correlated with HOMA-β in the Uygur male group (β = 2.101, P = 0.040) and negatively associated with BMI in all Uygur T2DM patients (Males: β = −1.563, P = 0.011; Females: β = −1.284, P = 0.016, respectively). No significant differences were observed between TOC and lipid profiles in all participants (all P > 0.05).ConclusionThere were differences in the associations between TOC and glucose metabolism in Han and Uygur T2DM patients, indicating genetic factors may play a role in modulating OC and glucose metabolism in different ethnic population.

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“…In a meta‐analysis assessing the association between OCN and T2DM, higher serum OCN was associated with a lower incidence of T2DM in cross‐sectional studies, whereas in cohort trials, the risk of T2DM was only marginally decreased in individuals with higher serum OCN . Several large‐scale human studies from Japan and China demonstrated that a lower baseline serum OCN level, for example, less than 6 ng/mL, was associated with increased risk of future development of T2DM and prediabetes . Thus, the predictive value of OCN with respect to incident dysglycaemia and diabetes should be further tested and verified in different ethnic populations …”

Section: Osteoblast‐derived Ocn As An Insulin Secretagogue and Insulimentioning

confidence: 99%

“…52 Several large-scale human studies from Japan and China demonstrated that a lower baseline serum OCN level, for example, less than 6 ng/mL, was associated with increased risk of future development of T2DM and prediabetes. [53][54][55] Thus, the predictive value of OCN with respect to incident dysglycaemia and diabetes should be further tested and verified in different ethnic populations. 47 It should be noted that only ucOC has metabolically active functions in mouse studies 6 and that the γ-carboxyglutamate (Gla) residuals of OCN differ between mice and humans.…”

Section: Osteoblast-derived Ocn As An Insulin Secretagogue and Insumentioning

confidence: 99%

Bone: Another potential target to treat, prevent and predict diabetes

Liu¹,

Mosialou

Liu

2018

Diabetes Obesity Metabolism

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Type 2 diabetes mellitus is now a worldwide health problem with increasing prevalence. Mounting efforts have been made to treat, prevent and predict this chronic disease. In recent years, increasing evidence from mice and clinical studies suggests that bone-derived molecules modulate glucose metabolism. This review aims to summarize our current understanding of the interplay between bone and glucose metabolism and to highlight potential new means of therapeutic intervention. The first molecule recognized as a link between bone and glucose metabolism is osteocalcin (OCN), which functions in its active form, that is, undercarboxylated OCN (ucOC). ucOC acts in promoting insulin expression and secretion, facilitating insulin sensitivity, and favouring glucose and fatty acid uptake and utilization. A second bone-derived molecule, lipocalin2, functions in suppressing appetite in mice through its action on the hypothalamus. Osteocytes, the most abundant cells in bone matrix, are suggested to act on the browning of white adipose tissue and energy expenditure through secretion of bone morphogenetic protein 7 and sclerostin. The involvement of bone resorption in glucose homeostasis has also been examined. However, there is evidence indicating the implication of the receptor activator of nuclear factor κ-B ligand, neuropeptide Y, and other known and unidentified bone-derived factors that function in glucose homeostasis. We summarize recent advances and the rationale for treating, preventing and predicting diabetes by skeleton intervention.

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Significant inverse association between serum osteocalcin and incident type 2 diabetes in a middle‐aged cohort

Cited by 19 publications

References 34 publications

Association of bone turnover markers with glucose metabolism in Chinese population

Association of bone turnover markers with glucose metabolism in Chinese population

Association between serum osteocalcin and glucose/lipid metabolism in Chinese Han and Uygur populations with type 2 diabetes mellitus in Xinjiang: two cross-sectional studies

Bone: Another potential target to treat, prevent and predict diabetes

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