Two major patterns of dynamics in adipokine serum concentrations over 2 years of dietary weight-loss intervention

M Blueher, A Rudich, N Kloeting, R Golan, E Rubin, D Schwarzfuchs, M Fiedler, Y Gepner, O Tangi, M Stampfer

Research output: Chapter in Book/Report/Conference proceedingConference contributionpeer-review


Background and aims: During dietary interventions, adipokines’ serum
concentrations may be affected by changes in adipose tissue mass and/or by
direct effects of healthier dieting. However, which are the adipokines that follow hormones and lipid parameters that mainly reflect weight changes, versus
those that are primarily affected by the dietary change that could persist beyond weight change is largely unknown.
Materials and methods: In the 2-year Dietary Intervention Randomized Controlled Trial (DIRECT) among patients with type 2 diabetes (T2D, n=45) and nondiabetics (n=277), which have been randomly assigned to one of three diets: lowfat, Mediterranean, or low-carbohydrate, we analyzed the dynamics in circulating
levels of adipokines, as well as serum concentrations of traditional biomarkers, and
their association with 2-year changes in homeostasis model assessment-insulin
resistance (HOMA-IR) and carotid artery intima-media thickness (IMT).
Results: Both qualitative analysis of the changes in biomarker levels at baseline, 6 and 24 months of intervention, and utilizing a non-biased mathematical modeling approach, revealed 2 major patterns of dynamics. Pattern A
included biomarkers whose dynamics closely reflect changes in body weight,
which exhibited a rapid decline (0-6 months) followed by weight stabilization
or regain (7-24 months). This pattern included fasting circulating levels of
insulin, triglycerides (TG), leptin, chemerin, monocyte chemoattractant protein-1 (MCP-1), and retinol binding protein-4 (RBP4). Pattern B consisted
of biomarkers that displayed a continuing, cumulative increase or decrease
throughout the 24 months of dietary intervention, despite the partial regain
in mean body weight. This group included high molecular weight (HMW)
adiponectin, HDL-cholesterol, CRP, fetuin-A, progranulin, and vaspin. Patterns A and B were similar among patients with T2D and non-diabetics. In
models adjusted for age, sex and assigned diet group, a greater decline in either chemerin (beta=0.136, p=0.034) or leptin (beta=0.250, p<0.001) within
the first 6 months of intervention were associated with lower levels of HOMAIR at 24 months. In multivariate models adjusted for age, sex, assigned diet
group, and 24 months changes in weight, chemerin, progranulin and MCP-1,
greater decrease in fetuin-A predicted a larger decline in IMT of the carotid
artery by the end of the 2 years intervention (beta = 0.201, p=0.040).
Conclusion: During a 2-year dietary intervention, leptin, chemerin, MCP-1 and
RBP4 corresponded mainly to body weight, similar to serum insulin and TG levels. In contrast, HMW adiponectin, fetuin-A, progranulin, and vaspin exhibited
cumulative improvement despite partial weight regain, similar to the changes in
HDL-cholesterol and CRP. The two patterns underscore weight -associated versus
healthy diet -induced beneficial effects beyond weight loss, and suggest a potential
predictive value for clinically-relevant metabolic and cardiovascular endpoints.
Original languageEnglish GB
Title of host publicationDIABETOLOGIA
StatePublished - 2010


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