Relationship between body adiposity, marrow adipose tissue and bone mass in human type 1 Diabetes Mellitus

Author(s)

Adriana Lelis Carvalho

• Document type: Doctoral Thesis
• Press: Ribeirão Preto.
• Institution: Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto (PCARP/BC)
• Defense date: 2017-02-14

Examining board members

Francisco Jose Albuquerque de Paula; Sonir Roberto Rauber Antonini; Marise Lazaretti Castro; Sérgio Atala Dib; Luiz Carlos Carvalho Navegantes

• Advisor: Francisco Jose Albuquerque de Paula

Abstract

Adipose tissue can impact differently depending on its localization and amount of stored fat. Marrow adipose tissue (MAT) expansion occurs in catabolic conditions associated with bone loss, such as anorexia nervosa and glucocorticoid therapy. Conversely, obesity is related to high or normal BMD and no change in MAT. Our aim was to evaluate the relationship of lipids depots with bone mass and MAT in conventionally treated T1D and T1D subjects submitted to hematopoietic stem cell transplantation (HSCT). The study comprised 3 groups matched by age, gender, height and weight: Control (13M/11F; 29±6 years; 67.4±14.4 Kg; 1.68±0.08 m; 23.8±3.7 Kg/m2), T1D (13M/10F; 32±13 years; 72.3±10.6 Kg; 1.69±0.08 m; 25.3±3.4 Kg/m2,17±11 years of diabetes duration) e T1D-HSCT (5M/4F; 25±6 years; 66.9±11 Kg; 1.72±0.11 m; 22.5±2.2 Kg/m2; 6 months to 10 years after HSCT). Blood samples were collected to evaluate glycemic control. BMD were assessed by DXA. 1-H magnetic resonance spectroscopy (1,5T) was used to evaluate MAT [fat/(fat+water) %] in L3 vertebrae. Subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), and intrahepatic lipids (IHL) were also evaluated by MRI. Only T1D exhibited poor metabolic control (HbA1c: Control=5.3±0.3%; T1D=9.6±2.2%; T1D-HSCT=6.4±0.5%; p<0,0001). Most T1D patients were overweighed (57%) and 1/3 of them had higher % body fat. BMD was similar between groups (e.g. L1-L4: Control=0.995±0.138 g/cm2; T1D=0.977±0.132 g/cm2; T1D-HSCT=0.971±0.115 g/cm2; p>0.05). Low bone mass (Z-score> -2,0 or T-score> -1,0) prevalence among individuals was 12,5% (n=3) in the Control group, 26% (n=6) in the T1D conventionally treated group and 11% (n=1) in the T1D-HSCT group. SAT was higher in T1D whereas there was no difference in VAT, IHL and MAT (Control: 34.4±11.7 %; T1D: 34.2±8.5%; T1D-HSCT: 40.3±8.5%; p>0.05). Also, there no difference in MAT lipid composition between groups (p>0.05). SAT had a positive association with femoral neck BMD (+0.0000055 g/cm2; p=0.02). Also, IHL had an inverse relationship with total hip and lumbar spine BMD (-0,012 g/cm2; p=0,03). Other factors such as age and glycemic control also had a negative impact on bone mass. There was a positive correlation between VAT and IHL (r=0,40) whereas no association between IHL and MAT was found (+0.226%, p>0.05). Cholesterol (+0,09%; p=0,0006) was an important preditor of MAT in L3. Yet, age (+0,252%; p=0,0006) had a significant association with saturated fraction of MAT and male gender (-1,379%, p<0,0001) was a negative factor for the unsaturated fraction of MAT. Moreover, MAT did not have any association with lumbar spine BMD (-0,002 g/cm2; p=0,16). Therefore, T1D bone mass was preserved and there were no changes in MAT content, independently of clinical treatment. This could be related to the nutritional status of T1D subjects. SAT accumulation was higher in T1D conventionally treated subjects compared to T1D-HSCT individuals probably due to more intense peripheral hyperinsulinemia. On the other hand, there was no increase in VAT and IHL between groups. The increase in SAT associated with higher BMD whereas it was not observed any relationship between VAT and bone mass. MAT did not have a deleterious impact on bone mass. However, cholesterol was a better predictor of MAT and its saturation compared to glycemic control. Further studies are required to better understand nutritional role and bone-fat interactions in T1D condition. (AU)

• FAPESP's process: 13/09853-6 - Relationship between visceral, hepatic and bone adiposity with bone mineral density and fracture occurrence in type 1 diabetes mellitus.
• Grantee: Adriana Lelis Carvalho
• Support Opportunities: Scholarships in Brazil - Doctorate