scholarly journals THE IMPACT OF TYPE 1 DIABETES MELLITUS ON BONE HEALTH IN CHILDREN

Author(s):  
Marco Janner ◽  
Christoph Saner

This paper gives an overview of the impact of type 1 diabetes on bone health in children and adolescents. First, we analyse studies using DXA (dual x-ray absorptiometry) to assess BMC (bone mineral content) and BMD (bone mineral density). Then, we discuss modern, non-invasive techniques including pQCT (peripheral quantitative computer tomography) and HRpQCT (high-resolution peripheral quantitative computer tomography) for the detailed assessment of bone health aspects including bone mass, bone geometry, bone microarchitecture and bone strength. Thereafter, we explore some of the mechanisms that are responsible for diabetic bone disease in children, like low bone turnover and high sclerostin levels. Finally, we summarise some of the evidence for the importance of microvascular disease in the pathophysiology of diabetic bone disease.

2020 ◽  
Vol 8 (1) ◽  
pp. e001384 ◽  
Author(s):  
Gitte Fuusager ◽  
Nikolaj Milandt ◽  
Vikram Vinod Shanbhogue ◽  
Anne Pernille Hermann ◽  
Anders Jørgen Schou ◽  
...  

IntroductionPatients with type 1 diabetes has an increased risk of fracture. We wished to evaluate estimated bone strength in children and adolescents with type 1 diabetes and assess peripheral bone geometry, volumetric bone mineral density (vBMD) and microarchitecture.Research design and methodsIn a cross-sectional study, high-resolution peripheral quantitative CT (HR-pQCT) was performed of the radius and tibia in 84 children with type 1 diabetes and 55 healthy sibling controls. Estimated bone strength was assessed using a microfinite element analysis solver. Multivariate regression analyses were performed adjusting for age, sex, height and body mass index.ResultsThe median age was 13.0 years in the diabetes group vs 11.5 years in healthy sibling controls. The median (range) diabetes duration was 4.2 (0.4−15.9) years; median (range) latest year Hb1Ac was 7.8 (5.9−11.8) % (61.8 (41−106) mmol/mol). In adjusted analyses, patients with type 1 diabetes had reduced estimated bone strength in both radius, β −390.6 (−621.2 to −159.9) N, p=0.001, and tibia, β −891.9 (−1321 to −462.9) N, p<0.001. In the radius and tibia, children with type 1 diabetes had reduced cortical area, trabecular vBMD, trabecular number and trabecular bone volume fraction and increased trabecular inhomogeneity, adjusted p<0.05 for all. Latest year HbA1c was negatively correlated with bone microarchitecture (radius and tibia), trabecular vBMD and estimated bone strength (tibia).ConclusionChildren with type 1 diabetes had reduced estimated bone strength. This reduced bone strength could partly be explained by reduced trabecular bone mineral density, adverse microarchitecture and reduced cortical area. We also found increasing latest year HbA1c to be associated with several adverse changes in bone parameters. HR-pQCT holds potential to identify early adverse bone changes and to explain the increased fracture risk in young patients with type 1 diabetes.


2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Volha V. Zhukouskaya ◽  
Alla P. Shepelkevich ◽  
Iacopo Chiodini

Type 1 diabetes (T1D) is autoimmune disease with chronic hyperglycaemic state. Besides diabetic retinopathy, nephropathy, and neuropathy, T1D is characterized by poor bone health. The reduced bone mineralization and quality/strength, due to hyperglycemia, hypoinsulinemia, autoimmune inflammation, low levels of insulin growth factor-1 (IGF-1), and vitamin D, lead to vertebral/hip fractures. Young age of T1D manifestation, chronic poor glycemic control, high daily insulin dose, low BMI, reduced renal function, and the presence of complications can be helpful in identifying T1D patients at risk of reduced bone mineral density. Although risk factors for fracture risk are still unknown, chronic poor glycemic control and presence of diabetic complications might raise the suspicion of elevated fracture risk in T1D. In the presence of the risk factors, the assessment of bone mineral density by dual-energy X-ray absorptiometry and the search of asymptomatic vertebral fracture by lateral X-ray radiography of thorax-lumbar spine should be recommended. The improvement of glycemic control may have a beneficial effect on bone in T1D. Several experiments showed promising results on using anabolic pharmacological agents (recombinant IGF-1 and parathyroid hormone) in diabetic rodents with bone disorder. Randomized clinical trials are needed in order to test the possible use of bone anabolic therapies in humans with T1D.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Stefana Catalina Bilha ◽  
Letitia Leustean ◽  
Cristina Preda ◽  
Dumitru D. Branisteanu ◽  
Laura Mihalache ◽  
...  

Abstract Background Despite the increased fracture risk, bone mineral density (BMD) is variable in type 1 (T1D) and type 2 (T2D) diabetes mellitus. We aimed at comparing independent BMD predictors in T1D, T2D and control subjects, respectively. Methods Cross-sectional case-control study enrolling 30 T1D, 39 T2D and 69 age, sex and body mass index (BMI) – matched controls that underwent clinical examination, dual-energy X-ray absorptiometry (BMD at the lumbar spine and femoral neck) and serum determination of HbA1c and parameters of calcium and phosphate metabolism. Results T2D patients had similar BMD compared to T1D individuals (after adjusting for age, BMI and disease duration) and to matched controls, respectively. In multiple regression analysis, diabetes duration – but not HbA1c- negatively predicted femoral neck BMD in T1D (β= -0.39, p = 0.014), while BMI was a positive predictor for lumbar spine (β = 0.46, p = 0.006) and femoral neck BMD (β = 0.44, p = 0.007) in T2D, besides gender influence. Age negatively predicted BMD in controls, but not in patients with diabetes. Conclusions Long-standing diabetes and female gender particularly increase the risk for low bone mass in T1D. An increased body weight partially hinders BMD loss in T2D. The impact of age appears to be surpassed by that of other bone regulating factors in both T1D and T2D patients.


Author(s):  
Melina Bezerra Loureiro ◽  
Marcela Abbott Galvão Ururahy ◽  
Karla Simone Costa de Souza ◽  
Yonara Monique da Costa Oliveira ◽  
Heglayne Pereira Vital da Silva ◽  
...  

2021 ◽  
Author(s):  
Phoebe Loxton ◽  
Kruthika Narayan ◽  
Craig F Munns ◽  
Maria E Craig

<u>Background</u> <p>There is substantial evidence that adults with type 1 diabetes have reduced bone mineral density (BMD), however findings in youth are inconsistent.</p> <p><u>Purpose</u></p> <p>Systematic review and meta-analysis of BMD in youth with type 1 diabetes using multiple modalities: dual energy X-ray absorptiometry (DXA), peripheral quantitative computed tomography (pQCT) and/or quantitative ultrasound (QUS).</p> <p><u>Data Sources</u></p> <p>PubMed, Embase, Scopus and Web of Science from 01/01/1990 to 31/12/2020, limited to humans, without language restriction.</p> <p><u>Study Selection</u></p> <p>Inclusion criteria: cross sectional or cohort studies that included BMD measured either by DXA, pQCT and/or QUS in youth (age <20 years) with type 1 diabetes and matched controls. </p> <p><u>Data extraction</u></p> <p>Total body (TB), lumbar spine (LS) and femoral BMD (DXA); tibia, radius and lumbar spine (pQCT); and phalanx and calcaneum (QUS). Weighted mean difference (WMD) or standardized mean difference (SMD) were estimated and meta-regression was performed using age, diabetes duration and HbA1c as covariates.</p> <p><u>Data Synthesis </u></p> <p>We identified 1300 non-duplicate studies; 46 met the inclusion criteria, including 2617 cases and 3851 controls. Mean age was 12.6 ± 2.3 years. Youth with type 1 diabetes had lower BMD: TB (WMD -0.04 g/cm<sup>2</sup>, 95% CI -0.06 to -0.02, <i>P</i>=0.0006); LS (-0.02 g/cm<sup>2</sup>, -0.03 to -0.0, <i>P = 0.01</i>); femur (-0.04 g/cm<sup>2</sup>, -0.05 to -0.03, <i>P</i><0.00001); tibial trabecular (-11.32 g/cm<sup>3</sup>,-17.33 to -5.30, <i>P</i>=0.0002), radial trabecular (-0.91, -1.55 to -0.27, <i>P=0.005</i>); phalangeal (-0.32, -0.38 to -0.25, <i>P</i><0.00001) and calcaneal (SMD -0.69, -1.11 to -0.26, <i>P</i>=0.001). Using meta-regression TB BMD was associated with older age (coefficient -0.0063, -0.0095 to -0.0031, <i>P</i>=0.002), but not longer diabetes duration or HbA1c.</p> <p><u>Limitations</u></p> <p>Meta-analysis was limited by the small number of studies using QUS and pQCT and lack of use BMD z-scores in all studies. </p> <p><u>Conclusions</u></p> <p>Bone development is abnormal in youth with type 1 diabetes, assessed by multiple modalities. Routine assessment of BMD should be considered in all youth with type 1 diabetes.</p>


2018 ◽  
Vol 4 (4) ◽  
pp. 37 ◽  
Author(s):  
Giuseppina E. Grieco ◽  
Dorica Cataldo ◽  
Elena Ceccarelli ◽  
Laura Nigi ◽  
Giovanna Catalano ◽  
...  

Type 1 diabetes (T1D) is characterized by bone loss and altered bone remodeling, resulting into reduction of bone mineral density (BMD) and increased risk of fractures. Identification of specific biomarkers and/or causative factors of diabetic bone fragility is of fundamental importance for an early detection of such alterations and to envisage appropriate therapeutic interventions. MicroRNAs (miRNAs) are small non-coding RNAs which negatively regulate genes expression. Of note, miRNAs can be secreted in biological fluids through their association with different cellular components and, in such context, they may represent both candidate biomarkers and/or mediators of bone metabolism alterations. Here, we aimed at identifying miRNAs differentially expressed in serum of T1D patients and potentially involved in bone loss in type 1 diabetes. We selected six miRNAs previously associated with T1D and bone metabolism: miR-21; miR-24; miR-27a; miR-148a; miR-214; and miR-375. Selected miRNAs were analyzed in sera of 15 T1D patients (age: 33.57 ± 8.17; BMI: 21.4 ± 1.65) and 14 non-diabetic subjects (age: 31.7 ± 8.2; BMI: 24.6 ± 4.34). Calcium, osteocalcin, parathormone (PTH), bone ALkaline Phoshatase (bALP), and Vitamin D (VitD) as well as main parameters of bone health were measured in each patient. We observed an increased expression of miR-148a (p = 0.012) and miR-21-5p (p = 0.034) in sera of T1D patients vs non-diabetic subjects. The correlation analysis between miRNAs expression and the main parameters of bone metabolism, showed a correlation between miR-148a and Bone Mineral Density (BMD) total body (TB) values (p = 0.042) and PTH circulating levels (p = 0.033) and the association of miR-21-5p to Bone Mineral Content-Femur (BMC-FEM). Finally, miR-148a and miR-21-5p target genes prediction analysis revealed several factors involved in bone development and remodeling, such as MAFB, WNT1, TGFB2, STAT3, or PDCD4, and the co-modulation of common pathways involved in bone homeostasis thus potentially assigning a role to both miR-148a and miR-21-5p in bone metabolism alterations. In conclusion, these results lead us to hypothesize a potential role for miR-148a and miR-21-5p in bone remodeling, thus representing potential biomarkers of bone fragility in T1D.


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