Abstract
Aims
Increased adiposity confers elevated risk for diabetic kidney disease (DKD) progression
in type 2 diabetes mellitus (T2DM). This 3-year prospective study examined whether
worsening of metabolic control e.g. development of uncontrolled diabetes mediated
the relationship between increased adiposity and DKD deterioration.
Methods
T2DM subjects who had adequately controlled diabetes (HbA1c < 8%) at initial recruitment
were analysed (N = 853). HbA1c ≥ 8% at follow-up was classified as development of
uncontrolled T2DM. Absolute changes in body weight (ΔWeight), body mass index (ΔBMI),
and body fat mass (ΔBFM) were calculated by subtracting baseline from follow-up values.
DKD deterioration (outcome) was defined as an increase in the composite ranking of
relative risk by glomerular filtration rate and albuminuria levels (Kidney Disease:
Improving Global Outcomes 2009).
Results
Subjects with deteriorated DKD displayed lower reduction in body composition at follow-up
than those who remained stable or/improved (all P < 0.05). In separate regression models, ΔWeight (risk ratio (RR):1.04, 95% CI:1.01–1.06),
ΔBMI (RR:1.07, 95% CI:1.01–1.13), and ΔBFM (RR:1.03, 95% CI:1.01–1.06) were independently
associated with worsened DKD. The associations were attenuated after accounting for
the loss of glycaemic control. Binary mediation analysis revealed that the development
of uncontrolled diabetes explained 41.7%, 45.4% and 39.7%, respectively, of the effects
of ΔWeight, ΔBMI and ΔBFM on the outcome.
Conclusions
Among T2DM individuals who had adequately-controlled T2DM at initial recruitment,
the relationship between gain in adiposity and DKD deterioration is mediated by the
development of poor glycaemic control over time. Therefore, preventing worsening adiposity
and hyperglycaemia is pivotal to impede DKD progression.
Keywords
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Article info
Publication history
Published online: August 08, 2019
Accepted:
August 6,
2019
Received in revised form:
July 15,
2019
Received:
February 18,
2019
Identification
Copyright
© 2019 Published by Elsevier B.V.
