Role of reduced insulin-stimulated bone blood flow in the pathogenesis of metabolic insulin resistance and diabetic bone fragility

Hinton, Pamela S.

doi:10.1016/j.mehy.2016.05.008

Cited by 11 publications

(7 citation statements)

References 62 publications

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“…e institutionalized group comprised only patients with well-controlled diabetes without late-stage complications. ere was some difference in the serum concentration of vitamin D between the three groups of patients, where vitamin D acted by stimulating intestinal absorption of calcium and phosphorus [5], as evident by the correlation between the Ca 2+ and 25(OH)D level for T1DM (R � 0.507; p � 0.001); for T2DM (R � 0.277; p � 0.01).Consequently, vitamin D regulates calcium and phosphorus homeostasis.…”

Section: Discussionmentioning

confidence: 98%

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Alterations of Bone Metabolism in Patients with Diabetes Mellitus

Safarova

2019

International Journal of Endocrinology

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Aim. The study aims to develop a practical model for screening bone turnover state in patients with diabetes and evaluate its clinical usefulness to identify diabetic osteopathy. Materials. The study was conducted in 2015–2017 in the Endocrinology Department of the Therapeutic Clinic of AM University. A total of 235 patients were assessed in the study (98 with T1DM and 137 with T2DM). 89 nondiabetic subjects served as controls. Bone mineral density (BMD) [by dual energy X-ray absorptiometry (DXA)] and serum markers of bone remodeling [aminoterminal propeptide of procollagen type I (P1NP) and c-terminal telopeptide of type I collagen (CTX)], parathyrin, and 25(OH)D were measured in all 235 patients. Results. Our results show that patients with T2DM have lower b-CTx values and relatively higher levels of P1NP, reflecting less pronounced changes in bone metabolism compared to patients with T1DM, regardless of age or duration of the disease. Osteoporosis was detected in 50% of patients with T1DM, compared to 13% of patients with T2DM. Conclusion. In some cases, bone remodeling markers are useful for improving the assessment of the state of bone tissue in early stages of diabetes, while alterations in bone microarchitecture may not always be captured by bone mineral density measurements.

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Section: Discussionmentioning

confidence: 98%

“…Changes in bone tissue metabolism in patients with type 2 diabetes occur somewhat differently [3,4]. e risk of developing fractures is 10-30% higher in T2DM patients than in those without diabetes that were matched for age [4][5][6]. Age-related bone loss increases the risk of fracture in the geriatric population (≥65 years).…”

Section: Introductionmentioning

confidence: 99%

Alterations of Bone Metabolism in Patients with Diabetes Mellitus

Safarova

2019

International Journal of Endocrinology

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“…An inverse association of fasting insulin with periosteal circumference has been reported in healthy adolescents 14 , 15 , and insulin resistance correlated inversely with periosteal and endosteal circumference 16 , 17 . Other putative indirect mechanisms whereby insulin resistance may affect bone involve a suggested role of hyperinsulinemia in bone ageing 18 , 19 , reduced blood flow to the bone tissue adversely affecting bone remodeling 19 and it has been shown that osteoblast-specific disruption of the insulin receptor leads to impaired osteoblast differentiation and reduced trabecular bone formation 20 , 21 . Experimental studies indicated that similar to skeletal muscle, hepatic, and adipose tissue, insulin resistance can develop in bone tissue, and that this compromised insulin signaling is associated with decreased bone remodeling 22 .…”

Section: Discussionmentioning

confidence: 99%

Effect of soy on bone turn-over markers in men with type 2 diabetes and hypogonadism – a randomised controlled study

Sathyapalan

Aye

Rigby

et al. 2017

Sci Rep

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Type 2 diabetes (T2DM) is associated with increased risk of fractures. Soy supplementation has been shown to have a beneficial effect on bone turnover markers (BTM) in postmenopausal women. However, the effect of soy supplementation on BTM in T2DM and particularly in men is unclear. We performed an analysis of a randomized double blind parallel study of 200 men with T2DM treated with soy, either with or without isoflavones. Outcome measures were type I collagen crosslinked beta C-telopeptide (βCTX), and type 1 procollagen-N-propeptide (P1NP). The men, with a total testosterone <12 nmol/L, were treated with 15 g soy protein containing 66 mg of isoflavones (SPI) or 15 g soy protein alone without isoflavones (SP) daily for three months. There was a 15% reduction in βCTX after three months of SPI compared to SP supplementation. There was no significant difference in P1NP with either SPI or SP supplementation. There was a significant linear correlation between the reduction in βCTX in the SPI group with the reduction in HbA1c (r 2 = 0.42; p = 0.04) and HOMA-IR (r 2 = 0.54; p = 0.02). Our study indicates that there was a significant reduction in bone resorption following 3 months of SPI supplementation that correlated with an improvement of glycemic control in men with T2DM.There is substantial epidemiological evidence that people with T2DM has increased risk of fractures 1,2 . This increase in fracture risk occurs despite bone mineral density (BMD) being comparatively higher in those with T2DM than those without. In a meta-analysis, Vestergaard reported an increased Z-score of 0.41 at the spine and 0.27 at the hip associated with T2DM 2 . T2DM has been shown to be an independent risk factor for fractures, which is not attributable to increased body mass index (BMI) or other classical osteoporosis risk factors 3 .Testosterone is anabolic for bone primarily through its aromatization to estrogen in adipose tissue 4 . Low testosterone in the setting of low or inappropriately normal luteinizing hormone and follicle-stimulating hormone is common in the diabetes population and may contribute to impaired bone strength in these men with T2DM 5 .Production and consumption of soy foods within Western countries have increased dramatically with postulated health benefits including improvement in bone health, especially in women 6 . Habitual intake of soy isoflavones has also been associated with a reduced risk of T2DM and cardiovascular disease (CVD) 7 .Bone turnover markers (BTMs) are biomarkers for fracture risk that have been used for the evaluation of effects of osteoporosis treatments, and include both bone resorption markers (e.g. type I collagen crosslinked Beta C-telopeptide (βCTX)) and bone formation markers (e.g. type I procollagen-N-propeptide (PINP)). Hypogonadal men with type 2 diabetes have smaller bone size and lower bone turn over 8 . We conducted this analysis to study the effect of soy isoflavone supplementation on BTMs in men with T2DM and low testosterone levels (<12 nmol/L).

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“…Other putative indirect mechanisms whereby insulin resistance may affect bone geometry involve a suggested role of hyperinsulinemia in bone ageing (35,36), and reduced blood flow to the bone tissue, which in turn adversely affects bone remodeling (37).…”

Section: Discussionmentioning

confidence: 99%

Insulin Resistance Is Associated With Smaller Cortical Bone Size in Nondiabetic Men at the Age of Peak Bone Mass

Verroken

Zmierczak

Goemaere

et al. 2016

The Journal of Clinical Endocrinology &Amp; Metabolism

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Context: In type 2 diabetes mellitus, fracture risk is increased despite preserved areal bone mineral density. Although this apparent paradox may in part be explained by insulin resistance affecting bone structure and/or material properties, few studies have investigated the association between insulin resistance and bone geometry.Objective: We aimed to explore this association in a cohort of nondiabetic men at the age of peak bone mass.Design, Setting, and Participants: Nine hundred ninety-six nondiabetic men aged 25 to 45 years were recruited in a cross-sectional, population-based sibling pair study at a university research center.Main Outcome Measures: Insulin resistance was evaluated using the homeostasis model assessment of insulin resistance (HOMA-IR), with insulin and glucose measured from fasting serum samples. Bone geometry was assessed using peripheral quantitative computed tomography at the distal radius and the radial and tibial shafts.Results: In age-, height-, and weight-adjusted analyses, HOMA-IR was inversely associated with trabecular area at the distal radius and with cortical area, periosteal and endosteal circumference, and polar strength strain index at the radial and tibial shafts ( b # 20.13, P , 0.001). These associations remained essentially unchanged after additional adjustment for dual-energy X-ray absorptiometry-derived body composition, bone turnover markers, muscle size or function measurements, or adiponectin, leptin, insulin-like growth factor 1, or sex steroid levels. Conclusion:In this cohort of nondiabetic men at the age of peak bone mass, insulin resistance is inversely associated with trabecular and cortical bone size. These associations persist after adjustment for body composition, muscle size or function, or sex steroid levels, suggesting an independent effect of insulin resistance on bone geometry. (J Clin Endocrinol Metab 102: [1807][1808][1809][1810][1811][1812][1813][1814][1815] 2017) T he prevalence of type 2 diabetes mellitus (T2DM) has reached epidemic proportions. In addition to wellknown microvascular and macrovascular complications, skeletal fragility is being increasingly recognized as another important diabetes-associated condition. Indeed, despite having a comparable areal bone mineral density (aBMD) as measured by dual-energy X-ray absorptiometry (DXA), individuals with T2DM present with an Abbreviations: 25(OH)D, 25-hydroxyvitamin D; aBMD, areal bone mineral density; CSA, cross-sectional area; CTX, C-terminal telopeptide of type I collagen; CV, coefficient of variation; DXA, dual-energy X-ray absorptiometry; EC PC , endosteal circumference additionally adjusted for periosteal circumference; FE2, free estradiol; FT, free testosterone; HOMA-IR, homeostasis model assessment of insulin resistance; IGF-1, insulin-like growth factor 1; P1NP, procollagen type 1 N-terminal propeptide; pQCT, peripheral quantitative computed tomography; PTH, parathyroid hormone; SHBG, sex hormone-binding globulin; SSIp, polar strength strain index; T2DM, type 2 diabetes mellitus; v...

show abstract

Role of reduced insulin-stimulated bone blood flow in the pathogenesis of metabolic insulin resistance and diabetic bone fragility

Cited by 11 publications

References 62 publications

Alterations of Bone Metabolism in Patients with Diabetes Mellitus

Alterations of Bone Metabolism in Patients with Diabetes Mellitus

Effect of soy on bone turn-over markers in men with type 2 diabetes and hypogonadism – a randomised controlled study

Insulin Resistance Is Associated With Smaller Cortical Bone Size in Nondiabetic Men at the Age of Peak Bone Mass

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