Determinants of undercarboxylated and carboxylated osteocalcin concentrations in type 1 diabetes

Thrailkill, Kathryn M.; Jo, Chan‐Hee; Cockrell, Gael; Moreau, Cynthia; Lumpkin, Charles K.; Fowlkes, John L.

doi:10.1007/s00198-011-1807-7

Cited by 46 publications

(32 citation statements)

References 33 publications

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“…However, ucOC levels in patients with T1DM did not differ from those in healthy adults. ucOC levels were higher in younger subjects and correlated positively with IGF1 (64). In healthy children, higher ucOC levels were associated with higher insulin secretion (65) as well as with higher high-molecular weight adiponectin, while children with prediabetes had lower ucOC concentrations and b-cell dysfunction (66).…”

Section: Clinical Evidence From Measurement Of Ucocmentioning

confidence: 99%

MECHANISMS IN ENDOCRINOLOGY: The endocrine role of the skeleton: background and clinical evidence

Schwetz

Pieber²,

Obermayer-Pietsch

2012

European Journal of Endocrinology

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Based on the observation that diabetes, obesity, and hypogonadism influence bone metabolism, the existence of a feedback loop and a common regulation was postulated and an endocrine role ascribed to the skeleton. In the first part of this review, two pathways are described whereby adipose tissue acts on bone mass. In the first, leptin activates the sympathetic nervous system via serotonin and diminishes bone mass accrual. The second pathway functions via the activation of CART (CARTPT) and inhibits bone resorption. The first pathway leads to a decrease in bioactivity of the osteoblast-produced hormone osteocalcin (OC) (part 2). In its undercarboxylated form, OC acts on the three targets pancreas, adipose tissue, and gonads (part 3) and thereby causes an increase in insulin secretion and sensitivity, b-cell proliferation, and male fertility. Insulin (part 4) is part of a recently discovered regulatory feedback loop between pancreas and osteoblasts. It is a strong counterplayer of leptin as it causes a decrease in OPG expression and enhances bone resorption and OC decarboxylation. Numerous clinical studies (part 5) have shown associations of total and undercarboxylated OC and markers of energy metabolism. Interventional studies, to date only performed in murine models, have shown positive effects of OC administration on energy metabolism. Whether bone tissue has an even further-reaching endocrine role remains to be elucidated. European Journal of Endocrinology 166 959-967

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Section: Clinical Evidence From Measurement Of Ucocmentioning

confidence: 99%

MECHANISMS IN ENDOCRINOLOGY: The endocrine role of the skeleton: background and clinical evidence

Schwetz

Pieber²,

Obermayer-Pietsch

2012

European Journal of Endocrinology

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“…A finding of low bone formation markers in association with T1D has been reported in most [35, 38, 47•, 50, 67, 68•, 69, 70], but not all studies [29]. Results for bone resorption markers have been variable, with most studies reporting normal levels [35, 38, 50, 70, 71], and others finding lower [47•, 59•, 72], or in one case higher levels [69] in T1D participants compared to controls. A cross-sectional study in adults identified an inverse relationship between non-fasting glucose and P1NP and CTX [73], and a longitudinal study in children found an inverse relationship between HbA1c and OCN and CTX [67], suggesting a negative effect of hyperglycemia on bone turnover.…”

Section: Introductionmentioning

confidence: 99%

Epidemiology of Skeletal Health in Type 1 Diabetes

Weber

Schwartz

2016

Curr Osteoporos Rep

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The skeleton is adversely affected by type 1 diabetes (T1D). Patients with T1D of both sexes have an increased risk of fracture that begins in childhood and extends across the entire lifespan. T1D is characterized by mild to modest deficits in bone density, structure, and microarchitecture. Current evidence suggests that the observed bone deficits in T1D are the result of impaired bone formation rather than increased bone resorption. There is emerging data that bone quality is impaired in T1D, which may explain the findings that fracture risk is elevated out of proportion to the degree of bone mineral deficit. In this review, we summarize the current knowledge regarding the epidemiology of skeletal health in T1D. Given the high individual and societal burden of osteoporotic fracture, there is an urgent need to better understand the etiology of T1D-related bone disease so that clinical strategies to prevent fracture can be developed.

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“…Because IGF-I mediates a number of osteo-promoting actions within skeletal tissues [4], deficiencies of IGF-I could contribute to skeletal abnormalities observed in T1D. IGF-I concentrations correlate positively with serum markers of bone formation in humans with T1D and IGF-I concentrations are lowest in osteopenic diabetic individuals compared to those without osteopenia [5–7]. Nevertheless, the role that IGF-I may play in the pathogenesis and/or prevention of T1D skeletal deficits has not been fully established.…”

Section: 1 Introductionmentioning

confidence: 99%

Osteo-promoting effects of insulin-like growth factor I (IGF-I) in a mouse model of type 1 diabetes

Fowlkes

Nyman

Bunn

et al. 2013

Bone

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Objective Using a streptozotocin (STZ)-induced mouse model of type 1 diabetes (T1D), we have previously demonstrated that long-term diabetes inhibits regenerative bone formation during tibial distraction osteogenesis (DO) and perturbs skeletal integrity by decreasing cortical thickness, bone mineral density and bone’s resistance to fracture. Because long-standing T1D is also associated with a deficiency of insulin-like growth factor I (IGF-I), we examined the effects of systemic IGF-I treatment on skeletal microarchitecture and strength, as well as on bone formation in diabetic mice. Research Design and Methods Streptozotocin-induced diabetic or control mice were treated with recombinant human IGF-I (rhIGF-I, 1.5 mg/kg/day as subcutaneous infusion) or vehicle throughout a 14 day DO procedure. Thereafter, trunk blood was assayed for glucose, insulin, rhIGF-I, mouse IGF-I and leptin. Bone formation in distracted tibiae was quantified. Effects on cortical bone strength and trabecular bone architecture were assessed by µCT analysis and three-point bend testing of contralateral femurs. Results New bone formation during DO was reduced in diabetic mice but significantly improved with rhIGF-I treatment. The contralateral femurs of diabetic mice demonstrated significant reductions in trabecular thickness, yield strength and peak force of cortical bone, which were improved with rhIGF-I treatment. rhIGF-I also reduced intracortical porosity in control mice. However, treatment with rhIGF-I did not normalize serum glucose, or correct concurrent deficiencies of insulin or leptin seen in diabetes. Conclusions These findings demonstrate that despite persistent hyperglycemia, rhIGF-I promoted new bone formation and improved biomechanical properties of bone in a model of T1D, suggesting that it may be useful as a fracture preventative in this disease.

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Determinants of undercarboxylated and carboxylated osteocalcin concentrations in type 1 diabetes

Cited by 46 publications

References 33 publications

MECHANISMS IN ENDOCRINOLOGY: The endocrine role of the skeleton: background and clinical evidence

MECHANISMS IN ENDOCRINOLOGY: The endocrine role of the skeleton: background and clinical evidence

Epidemiology of Skeletal Health in Type 1 Diabetes

Osteo-promoting effects of insulin-like growth factor I (IGF-I) in a mouse model of type 1 diabetes

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