Body composition in diabetes endotypes

Objective: New clustering approaches successfully distinguished between severe and moderate diabetes endotypes. It remains unclear if body composition differs between diabetes endotypes. We hypothesize that individuals with moderate age-related diabetes (MARD) (i) have a lower fat free mass index (FFMI) and a higher fat mass index (FMI) than would be expected from their BMI, sex and age, and (ii) exhibit worsening of their phenotype during the early course of diabetes.

Methods: Body composition was measured by bioelectrical impedance analysis in participants of the prospective German Diabetes Study (GDS; n=864, BMI 29±7 kg/m2, age 47±13 y, known diabetes duration<1 y). FFMI (kg/m2) and FMI (kg/m2) were expressed as standard deviation score (SDS) for BMI, age and sex using reference data from a population without diabetes (n=1958, BMI 17-46 kg/m2, age 18-97 y). In people with weight changes ( > 2 kg) during 5-years, changes in FFM during weight changes (∆FFM/∆ body weight) were assessed using the deviation from body composition predicted by Hall&apos;s formula, which corrects for the fact that changes in body composition depend on the initial fat mass.

Results: At baseline, people with moderate obesity-related diabetes (MOD; n=246) and severe insulin resistance diabetes (SIRD; n=57) had the highest BMI (35±5, 35±6 kg/m2), FMI [12.7(11.0; 15.7), 13.0(10.2; 16.2)] and FFMI [21.7(20.3; 22.8), 21.3(19.5; 23.1)] compared to other diabetes endotypes (all p<0.01). Normalization for BMI, age and sex revealed that MOD had the lowest FMI-SDS [-0.77(-1.18; -0.38)] compared to severe autoimmune diabetes [SAID; n=289; -0.40(-0.82; 0.04)], SIRD [- 0.37(-0.76; 0.14)], MARD [n=251; 0.14(-0.36; 062)] and severe insulin-deficient diabetes [SIDD; n=21; 0.03(-0.19; 0.58), all p<0.001]. By contrast, MARD had a higher FMI-SDS compared to SIRD (p<0.05), MOD and SAID (both p<0.001) as well as a lower FFMI-SDS [-0.05(-0.54; 0.46)] compared to MOD [0.83(0.44; 1.22), p<0.001] and SIRD [0.45(0.07; 0.912), p<0.05]. With weight gain, people with MOD had a higher ∆FFM/∆body weight than predicted (p<0.05), whereas changes did not differ from predicted values in SAID (p=0.46), SIRD (p=0.63) and MARD (p=0.09). With weight loss, ∆FFM/∆body weight was higher than predicted in SIRD (p<0.01), MOD and MARD (both p<0.001).

Conclusion: Interestingly, individuals with MARD are at highest risk for sarcopenia which might be relevant intensifying diagnostic measures and tailoring treatment strategies. The lower FMI-SDS and disproportionately higher increase in FFM with weight gain in people with MOD may explain their lower risk for diabetes-related complications compared to people with SIRD at a similar BMI.

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Artikel online veröffentlicht:
18. April 2024