Waist-height ratio and waist are the best estimators of visceral fat in type 1 diabetes

In this study, we investigated for the first time the body composition of individuals with type 1 diabetes with and without albuminuria. We showed that individuals with albuminuria, regardless of sex, had greater visceral fat percentage and lower appendicular lean mass percentage, which is a dangerous combination regarding the risk of CVD8,18,19. This finding is even more relevant if we consider that this population already has a high cardiovascular risk because of diabetes and DN1,3,20.We showed that individuals with similar BMI have very different body composition, especially concerning the percentage of visceral fat and lean mass. This result emphasizes the importance of knowing the body composition instead of only BMI in a high cardiovascular risk population. The increase in body weight with a central distribution favours the accumulation of visceral fat that leads to an inflammatory state and insulin resistance10, which has been associated with kidney disease11,12,21. To make the situation worse, low lean mass22 and kidney disease23 are also associated with muscle insulin resistance. Considering that this is a cross-sectional study, it is not possible to say if the visceral fat, which is linked to chronic inflammation and insulin resistance, is contributing to the development of albuminuria or the albuminuric stage is worsening the visceral fat and insulin resistance due to physical inactivity, inflammation, changes in the microbiome or other factors21.Most importantly, in this study, we found a strong association between VFM% and simple measures such as WHtR and WC, independently of the albuminuric stage and sex. We are not aware of any other study in individuals with type 1 diabetes that have previously assessed such relationships, especially looking at different stages of albuminuria. WHtR has been associated with central obesity and cardiovascular risk in the general population and in people with type 2 diabetes13,14,15. Furthermore, in a large prospective study including 109,536 postmenopausal women, it has been linked to cardiovascular events24. However, the relationship between WHtR and VFM% has never been described in individuals with type 1 diabetes with and without albuminuria. Given that DN increases cardiovascular mortality several-fold20,25 and that visceral fat is closely associated with CVD8, 18, our results regarding the association between WHtR and visceral fat are consistent with the literature which has shown the WHtR is a better screening tool than BMI for cardiometabolic risk factors16. Therefore, this study brings up new important information regarding central obesity in individuals with type 1 diabetes, a subject that most of the time has been related to type 2 diabetes. In this respect, it is important to acknowledge that obesity is increasing among individuals with type 1 diabetes and at the same time, there has been an increase in the mortality rate starting from a normal range of BMI1.Another novel finding of this study was the negative association between BLM% and WHtR and WC, independently of the albuminuric stage. Although BLM% was best estimated by WHtR in men and by BMI in women, the simple measurement of WC was the second-best for the estimation of BLM% in both sexes. A plausible explanation for why WC and WHtR can estimate the percentage of body lean mass is the negative association between BLM% and VFM%. Although a recent publication showed that the fat-free mass was not associated with CVD7, it does not exclude the relevance of our findings, since one has to take into consideration that the fat-free mass measured by bioimpedance includes not only the muscle mass and, in our study, we measured the body lean mass by DXA, which has better accuracy than the bioimpedance5. From a clinical perspective, we found a simple and accessible tool to estimate the body lean mass in individuals with type 1 diabetes, independently of albuminuria.Since low skeletal muscle mass is linked to CVD19 and muscle wasting has been associated with premature death in individuals with end-stage renal disease26 another important clinical finding was that, independently of sex, individuals with albuminuria have lower AppLM% compared to those without albuminuria, which might contribute to the increase in the cardiovascular risk of this high-risk population. Muscle wasting is not rare in individuals with end-stage renal disease26,27 and although we did not include such individuals in our analyses, we showed that individuals with type 1 diabetes at the earlier stages of DN (micro and macroalbuminuria) already show a decrease in their BLM% compared to those with normoalbuminuria.According to previous publications including individuals with obesity and/or type 2 diabetes, in the current study, the ABSI was positively associated with central obesity and negatively associated with body lean mass28,29. However, it was inferior to the other anthropometric measures for the estimation of BFM%, VFM% and BLM% in our sample composed by Caucasian-Finnish individuals with type 1 diabetes. Since ABSI is a formula composed by WC adjusted for weight and height, the association between ABSI and body composition may vary depending on the characteristics of the studied population and on ethnicity.In our study, BMI was not the anthropometric measure to best estimate VFM% in both sexes, and this inability of BMI to reflect the abdominal fat has been discussed erlier4. It was not useful to estimate BFM% and BLM% in men either, although it was in women. The relationship between BMI and BFM% was studied previously in the general population30 and the percentage of body fat mass related to the BMI was similar to our study. However, the American study30 did not investigate the associations between VFM%, BLM% with BMI, not either with WHtR and WC such as our study.Furthermore, BMI misclassified BFM% in 26% of the total cases and underestimated it in 21% of them. Although the level of misclassification by BMI in our study is lower than in a previous study31, it might be explained by the different methods used to assess the body composition. In the previous study, they used bioimpedance while we used DXA, which provides better accuracy5. However, such as misclassification is clinically relevant, since individuals considered to have normal body weight by BMI might, in fact, have an excess of body fat and visceral fat, which are both closely associated with cardiovascular mortality8,13,32,33. The misclassification by BMI is another possible explanation of why the mortality rate in individuals with type 1 diabetes starts to increase already from the normal range of BMI1 Interestingly, the WC and WHtR misclassify the BFM% at least similarly to BMI, although they are in fact measures to estimate the central fat and not the total body fat. This finding is clinically important since a simple measure of WHtR or WC could not only better estimate visceral fat than BMI, but was able to classify obesity (BFM%) as well as BMI.Another novelty of this study is to show, by our linear models, how much of the body fat mass and visceral fat mass percentages are related to the cut-offs of BMI, WC and WHtR. Interestingly, the BFM% and VFM% related to the BMI of 25 kg/m2 are similar to BFM% and VFM% related to the WHtR of 0.5. Therefore, our finding may provide a clue, why there is an increase in the mortality rate of this population starting from a BMI of 24.8 kg/m2 1. These results may question whether the BMI of 25 kg/m2 is the best cut-off to define central obesity and cardiovascular risk in individuals with type 1 diabetes.A limitation of this study is that we can not exclude confounding factors such as lifestyle and ethnicity. Since we studied a homogenous all-Caucasian Finnish population with type 1 diabetes and there are different thresholds for waist circumference and BMI for different ethnicities4,34, our results may not be applicable for all ethnicities. Another limitation is its cross-sectional design; therefore, it is not possible to conclude any causality between the associations we found nor any prediction of CVD risk. However, these results motivate further prospective studies to investigate the impact of body composition on chronic diabetes complications in individuals with type 1 diabetes. Another strength is its wide applicability to clinical practice since we here provide easily applicable tools to estimate the percentage of visceral fat and lean mass in a population with a high cardiovascular risk.In conclusion, this study shows that simple measures such as WHtR and WC can estimate the VFM% in adults with type 1 diabetes independently of albuminuric stage and sex. Furthermore, it showed that individuals with type 1 diabetes and albuminuria, a population of high CVD risk, have greater VFM% and lower AppLM% compared to those with normoalbuminuria. From the clinical perspective, this study supports the routine monitoring of WHtR in adults with type 1 diabetes.

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