Marrow adipose tissue composition in adults with morbid obesity

Abstract

Patients with type 2 diabetes mellitus (T2DM) have increased fracture risk despite normal or increased bone mineral density (BMD). Elevations in marrow adipose tissue (MAT) and declines in MAT unsaturation are both associated with increased skeletal fragility. The objective of our study was to characterize the quantity and composition of MAT in adults with morbid obesity and T2DM, and to evaluate determinants of MAT. We studied 21 adults with morbid obesity prior to bariatric surgery, 8 of whom had T2DM. All subjects underwent 1H-MR spectroscopy of the lumbar spine and femur for assessment of MAT and dual-energy x-ray absorptiometry (DXA) and quantitative computed tomography (QCT) of the lumbar spine and hip for assessment of areal BMD (aBMD) and volumetric BMD (vBMD). Visceral (VAT) and subcutaneous adipose tissue (SAT) were quantified by CT at L1-2. Subjects with T2DM had higher vBMD of the femoral neck and higher total MAT at the lumbar spine and femoral metaphysis compared to non-diabetic controls (p≤0.04). Lipid unsaturation index (UI) was significantly lower at the femoral diaphysis in T2DM (p=0.03). Within the entire cohort, HbA1c was positively associated with MAT (p≤0.03), and age was associated with higher MAT and lower MAT unsaturation (p≤0.05). Lumbar spine vBMD was inversely associated with lumbar spine MAT (p=0.04). There was an inverse association between SAT and diaphyseal MAT (p<0.05) while there were no associations with VAT. Subjects with morbid obesity and T2DM have higher MAT with a lower proportion of unsaturated lipids, despite higher femoral neck vBMD. MAT is positively associated with age and HbA1c, and inversely associated with vBMD, suggesting that MAT may serve as an imaging biomarker of skeletal health and metabolic risk.

Bone Marrow Fat Changes After Gastric Bypass Surgery Are Associated With Loss of Bone Mass

“…(22,23,48) In humans, marrow fat differences with diabetes are less clear, (32,43,49,50) although in one recent study of morbidly obese adults, participants with type 2 diabetes had higher amounts of marrow fat than nondiabetics. (51) Similarly, Baum and colleagues found in their study of 26 postmenopausal women (13 with type 2 diabetes and 13 ageand BMI-matched controls) that those with higher HbA1c levels had higher vertebral marrow fat content (r ¼ 0.83, p < 0.01). (24) In our study, we did not identify a higher mean marrow fat content among diabetic versus nondiabetic women, but our longitudinal findings support the influence of glucose metabolism on marrow fat.…”

“…Animal models of both type 1 and type 2 diabetes have demonstrated increased marrow fat and bone mass loss compared with controls . In humans, marrow fat differences with diabetes are less clear, although in one recent study of morbidly obese adults, participants with type 2 diabetes had higher amounts of marrow fat than nondiabetics . Similarly, Baum and colleagues found in their study of 26 postmenopausal women (13 with type 2 diabetes and 13 age‐ and BMI‐matched controls) that those with higher HbA1c levels had higher vertebral marrow fat content ( r = 0.83, p < 0.01) .…”

Insulin Signaling in Bone Marrow Adipocytes

“…1). Adults with morbid obesity and T2D, who have high serum insulin levels, exhibited higher total BMAT at the lumbar spine and femoral metaphysis compared with those without diabetes [23]. Thus, current literature suggests that alterations in insulin receptor function or insulin level regulate BMAT formation.…”

Energy Metabolism of Bone

“…Likewise, some have reported that increased MAT is not a feature in obese type 2 DM subject (de Araujo et al , 2017). Yet, others have described a greater MAT content in lumbar spine and femoral metaphysis of morbid obese subjects with type 2 DM using insulin therapy or anti-diabetic oral agents (Yu et al , 2017). This highlights that MAT function and its determinants in diabetes condition needs to be better understood.…”