Our study was undertaken to determine if a correlation existed between vertebral bone marrow fat content and abdominal adipose tissue, lumbar vBMD, and blood values in T2DM postmenopausal women and healthy controls. The results demonstrated that vertebral bone marrow fat content is inversely correlated with lumbar vBMD and positively correlated with subcutaneous and total abdominal adipose tissue in both subject groups. Moreover, we observed significant correlations of vertebral bone marrow fat content with visceral adipose tissue and HbA1c in postmenopausal women with T2DM, suggesting that vertebral bone marrow fat content may be a biomarker for how well diabetes is controlled.
Gallagher et al. reported significantly altered total body adipose tissue distribution in T2DM subjects with more VAT and less SAT compared to healthy controls (1
). These alterations of the adipose tissue distribution were not only observed in T2DM subjects but also in subjects with impaired glucose tolerance (21
). Heshka et al. found T2DM to be associated with less total fat, leg fat and leg lean mass and more truncal fat and lean mass than controls (3
). Our study showed similar abdominal SAT and higher abdominal VAT and TAT values in T2DM subjects compared to healthy controls. While these differences were non-significant, diabetic subjects had significantly higher VAT/TAT ratios than healthy controls. In addition, we found significant correlations between the mean vertebral bone marrow fat content and SATadj
and between the mean vertebral bone marrow fat content and TATadj
in both groups and combined for all subjects. Furthermore a significant correlation was found between mean vertebral bone marrow fat content and VATadj
in the diabetic subjects. These findings suggest an association between abdominal adipose tissue and vertebral bone marrow fat. Interestingly, Bredella et al. observed only a significant correlation between VAT and vertebral bone marrow fat in a previous study that included premenopausal women with normal weight, overweight and obesity (6
We found no significant correlations between abdominal adipose tissue and lumbar vBMD in either subject group, whereas significant correlations between adipose tissue and BMD in older persons were reported previously, partly demonstrating beneficial effects of subcutaneous and detrimental effects of visceral fat on bone strength (22
). The relatively small sample size in our study may explain why no significant correlations were found. In contrast to abdominal adipose tissue parameters, vertebral bone marrow fat content showed inverse correlations with lumbar vBMD in each group and combined for all subjects. Previous studies reported similar findings in men as well as pre- and postmenopausal women (6
). While most studies used DXA and performed 1
H-MRS only at one lumbar vertebra, we assessed volumetric BMD by using QCT and measured vertebral bone marrow fat content from L1–L3. These measurements may be more representative and also showed that a vBMD decrease from L1–L3 is associated with a corresponding vertebral bone marrow fat content increase in both subject groups. The possible effects of T2DM on the vertebral bone marrow fat are more difficult to address. Diabetic subjects and healthy controls were age- and BMI-matched and showed similar vBMD values (averaged over L1–L3: 135.60 ± 32.21 mg/ml vs. 129.46 ± 33.03 mg/ml) and similar vertebral bone marrow fat content (averaged over L1–L3: 69.3 ± 7.5% vs. 67.5 ± 6.1%). However, the mean vertebral bone marrow unsaturated lipid fraction was significantly lower in diabetic subjects compared to healthy controls (6.7 ± 1.0% vs. 7.9 ± 1.6%; p=0.006). We also observed a highly significant correlation (r=0.825; p<0.001) between vertebral bone marrow fat content and HbA1c levels in the diabetic subjects, suggesting an effect of T2DM on the vertebral bone marrow fat. This became more apparent when the diabetic subjects were stratified based on HbA1c levels with a cut-off point of 7% and significantly higher vertebral bone marrow fat content was found in subjects with HbA1c levels >7%. We chose this cut-off point, since targeting HbA1c levels <7% are recommended to reduce microvascular complications (31
). To our knowledge, this is the first study, which examined the relationship between HbA1c levels and vertebral bone marrow fat content in subjects with T2DM. We found no significant correlation between fasting plasma glucose level and vertebral bone marrow fat. Both HbA1c and fasting plasma glucose have their diagnostic value for T2DM (33
). However, HbA1c levels reflect a 2–3-month average of blood glucose concentrations in contrast to fasting plasma glucose as short-term marker (35
). That might be the reason why a significant correlation with vertebral bone marrow fat content was only found for HbA1c and not for fasting plasma glucose. The association of HbA1c levels and vertebral bone marrow fat content in subjects with T2DM may further our understanding of this metabolic disease, similar to findings of Bredella et al. who reported an inverse correlation between vertebral bone marrow fat content and insulin-like growth factor 1 (IGF-1) in obese women, supporting the role of IGF-1 as an important regulator of the fat and bone lineage (6
). In contrast to vertebral bone marrow fat content, no significant correlations of mean vertebral bone marrow unsaturated lipid fraction with vBMD, abdominal adipose tissue and HbA1c levels were found in either group (p>0.05). This may be explained by the relatively small unsaturated lipid fraction compared to the predominant saturated lipid fraction in the bone marrow spectrum.
We observed no differences of vitamin D, calcium and PTH levels in diabetic subjects and healthy controls. Vertebral bone marrow fat content and lumbar vBMD did not correlate with these blood values in our study, while previous studies reported associations between vitamin D status, parathyroid function and BMD (37
). This might be explained by the comparatively small study population with the focus on subjects with T2DM in our study.
Our study had several limitations. First, the sample size of our study was rather small with 13 diabetics and 13 controls. However, this was a pilot study and it was beyond the scope to apply this multi-modal study design to a large sample size. Further investigation with a larger sample size is needed in the future. Secondly, these results were reflected in T2DM postmenopausal women. It is unclear whether these correlations can be observed in younger, as well as male T2DM populations. Thirdly, our study population only included Asians and Caucasian patients. An additional study with African-Americans, who have been shown to have a high prevalence of T2DM, should be investigated in the future (39
). Fourthly, VAT may be overestimated due to inadequately assigned pixels (e.g. bowel content within the same attenuation range as VAT), which is a limitation of the study (41
). Lastly, reproducibility of the imaging modalities is critical, especially for 1
H-MRS. However, we demonstrated acceptable reproducibility errors, not only for 1
H-MRS, but for the abdominal fat segmentation of QCT images as well.
In conclusion, this study demonstrated that vertebral bone marrow fat content correlates significantly with abdominal adipose tissue and lumbar spine volumetric BMD in postmenopausal women with and without T2DM. The observed association of vertebral bone marrow fat content with HbA1c levels in T2DM subjects demonstrates an effect of T2DM on vertebral bone marrow fat content that suggests that bone marrow fat may be a biomarker for the extent of glycemic control and potentially for late diabetic complications. Further studies with larger cohorts will need to investigate the role of 1H-MRS based vertebral bone marrow fat quantitation in T2DM.