Glucose variability and low bone turnover in people with type 2 diabetes

Objective To investigate the differences in bone turnover between diabetic patients and controls. Design A systematic review and meta-analysis. Methods A literature search was conducted using the databases Medline at PubMed and EMBASE. The free text search terms ‘diabetes mellitus’ and ‘bone turnover’, ‘sclerostin’, ‘RANKL’, ‘osteoprotegerin’, ‘tartrate-resistant acid’ and ‘TRAP’ were used. Studies were eligible if they investigated bone turnover markers in patients with diabetes compared with controls. Data were extracted by two reviewers. Results A total of 2881 papers were identified of which 66 studies were included. Serum levels of the bone resorption marker C-terminal cross-linked telopeptide (−0.10 ng/mL (−0.12, −0.08)) and the bone formation markers osteocalcin (−2.51 ng/mL (−3.01, −2.01)) and procollagen type 1 amino terminal propeptide (−10.80 ng/mL (−12.83, −8.77)) were all lower in patients with diabetes compared with controls. Furthermore, s-tartrate-resistant acid phosphatase was decreased in patients with type 2 diabetes (−0.31 U/L (−0.56, −0.05)) compared with controls. S-sclerostin was significantly higher in patients with type 2 diabetes (14.92 pmol/L (3.12, 26.72)) and patients with type 1 diabetes (3.24 pmol/L (1.52, 4.96)) compared with controls. Also, s-osteoprotegerin was increased among patients with diabetes compared with controls (2.67 pmol/L (0.21, 5.14)). Conclusions Markers of both bone formation and bone resorption are decreased in patients with diabetes. This suggests that diabetes mellitus is a state of low bone turnover, which in turn may lead to more fragile bone. Altered levels of sclerostin and osteoprotegerin may be responsible for this.

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Decision letter for "Bone turnover markers do not predict fracture risk in type 2 diabetes"

10.1002/jbmr.4140/v3/decision1 ◽

2020 ◽

Keyword(s):

Type 2 Diabetes ◽

Bone Turnover ◽

Fracture Risk ◽

Bone Turnover Markers ◽

Turnover Markers ◽

Predict Fracture Risk

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Review for "Bone turnover markers do not predict fracture risk in type 2 diabetes"

10.1002/jbmr.4140/v1/review1 ◽

2019 ◽

Author(s):

Niklas Jørgensen

Keyword(s):

Type 2 Diabetes ◽

Bone Turnover ◽

Fracture Risk ◽

Bone Turnover Markers ◽

Turnover Markers ◽

Predict Fracture Risk

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Plasma heat shock protein response to euglycemia in type 2 diabetes

BMJ Open Diabetes Research & Care ◽

10.1136/bmjdrc-2020-002057 ◽

2021 ◽

Vol 9 (1) ◽

pp. e002057

Author(s):

Alexander S Atkin ◽

Abu Saleh Md Moin ◽

Ahmed Al-Qaissi ◽

Thozhukat Sathyapalan ◽

Stephen L Atkin ◽

...

Keyword(s):

Type 2 Diabetes ◽

Heat Shock ◽

Protein Interactions ◽

Glucose Variability ◽

Interacting Protein ◽

Ubiquitin Conjugating Enzyme ◽

Shock Proteins ◽

Protein Response ◽

Design And Methods

IntroductionGlucose variability is associated with mortality and macrovascular diabetes complications. The mechanisms through which glucose variability mediates tissue damage are not well understood, although cellular oxidative stress is likely involved. As heat shock proteins (HSPs) play a role in the pathogenesis of type 2 diabetes (T2D) complications and are rapidly responsive, we hypothesized that HSP-related proteins (HSPRPs) would differ in diabetes and may respond to glucose normalization.Research design and methodsA prospective, parallel study in T2D (n=23) and controls (n=23) was undertaken. T2D subjects underwent insulin-induced blood glucose normalization from baseline 7.6±0.4 mmol/L (136.8±7.2 mg/dL) to 4.5±0.07 mmol/L (81±1.2 mg/dL) for 1 hour. Control subjects were maintained at 4.9±0.1 mmol/L (88.2±1.8 mg/dL). Slow Off-rate Modified Aptamer-scan plasma protein measurement determined a panel of HSPRPs.ResultsAt baseline, E3-ubiquitin-protein ligase (carboxyl-terminus of Hsc70 interacting protein (CHIP) or HSPABP2) was lower (p=0.03) and ubiquitin-conjugating enzyme E2G2 higher (p=0.003) in T2D versus controls. Following glucose normalization, DnaJ homolog subfamily B member 1 (DNAJB1 or HSP40) was reduced (p=0.02) in T2D, with HSP beta-1 (HSPB1) and HSP-70-1A (HSP70-1A) (p=0.07 and p=0.09, respectively) also approaching significance relative to T2D baseline levels.ConclusionsKey HSPRPs involved in critical protein interactions, CHIP and UBE2G2, were altered in diabetes at baseline. DNAJB1 fell in response to euglycemia, suggesting that HSPs are reacting to basal stress that could be mitigated by tight glucose control with reduction of glucose variability.

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