ORCID Profile
0000-0002-6127-0448
Current Organisation
Steno Diabetes Center Copenhagen
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Publisher: Springer Science and Business Media LLC
Date: 25-05-2022
DOI: 10.1007/S00125-022-05716-3
Abstract: Lifestyle interventions are the first-line treatment option for body weight and cardiometabolic health management. However, whether age groups or women and men respond differently to lifestyle interventions is under debate. We aimed to examine age- and sex-specific effects of a low-energy diet (LED) followed by a long-term lifestyle intervention on body weight, body composition and cardiometabolic health markers in adults with prediabetes (i.e. impaired fasting glucose and/or impaired glucose tolerance). This observational study used longitudinal data from 2223 overweight participants with prediabetes in the multicentre diabetes prevention study PREVIEW. The participants underwent a LED-induced rapid weight loss (WL) period followed by a 3 year lifestyle-based weight maintenance (WM) intervention. Changes in outcomes of interest in prespecified age (younger: 25–45 years middle-aged: 46–54 years older: 55–70 years) or sex (women and men) groups were compared. In total, 783 younger, 319 middle-aged and 1121 older adults and 1503 women and 720 men were included in the analysis. In the available case and complete case analyses, multivariable-adjusted linear mixed models showed that younger and older adults had similar weight loss after the LED, whereas older adults had greater sustained weight loss after the WM intervention (adjusted difference for older vs younger adults −1.25% [95% CI −1.92, −0.58], p .001). After the WM intervention, older adults lost more fat-free mass and bone mass and had smaller improvements in 2 h plasma glucose (adjusted difference for older vs younger adults 0.65 mmol/l [95% CI 0.50, 0.80], p .001) and systolic blood pressure (adjusted difference for older vs younger adults 2.57 mmHg [95% CI 1.37, 3.77], p .001) than younger adults. Older adults had smaller decreases in fasting and 2 h glucose, HbA 1c and systolic blood pressure after the WM intervention than middle-aged adults. In the complete case analysis, the above-mentioned differences between middle-aged and older adults disappeared, but the direction of the effect size did not change. After the WL period, compared with men, women had less weight loss (adjusted difference for women vs men 1.78% [95% CI 1.12, 2.43], p .001) with greater fat-free mass and bone mass loss and smaller improvements in HbA 1c , LDL-cholesterol and diastolic blood pressure. After the WM intervention, women had greater fat-free mass and bone mass loss and smaller improvements in HbA 1c and LDL-cholesterol, while they had greater improvements in fasting glucose, triacylglycerol (adjusted difference for women vs men −0.08 mmol/l [−0.11, −0.04], p .001) and HDL-cholesterol. Older adults benefited less from a lifestyle intervention in relation to body composition and cardiometabolic health markers than younger adults, despite greater sustained weight loss. Women benefited less from a LED followed by a lifestyle intervention in relation to body weight and body composition than men. Future interventions targeting older adults or women should take prevention of fat-free mass and bone mass loss into consideration. ClinicalTrials.gov NCT01777893.
Publisher: Springer Science and Business Media LLC
Date: 13-04-2017
Publisher: Cold Spring Harbor Laboratory
Date: 19-02-2022
DOI: 10.1101/2022.02.16.480373
Abstract: Metformin is a blood glucose lowering medication with physiological effects that extend beyond its anti-diabetic indication. Recently, it was reported that metformin lowers body weight via induction of growth differentiation factor 15 (GDF15), which suppresses food intake by binding to the GDNF family receptor α-like (GFRAL) in the hindbrain. At the same time, we demonstrated that recombinant GDF15 suppresses voluntary exercise in a GFRAL-dependent fashion. Here, we corroborate that metformin increases circulating GDF15 in mice and humans, but that it does not reduce voluntary running activity in mice. Unexpectedly, we fail to confirm previous reports that the GDF15-GFRAL pathway is necessary for the weight-lowering effects of metformin. Instead, our studies in wild-type, GDF15 knockout and GFRAL knockout mice suggest that the GDF15-GFRAL pathway is dispensable for the effects of metformin on energy balance. The data presented here question whether metformin is a sufficiently strong stimulator of GDF15 to drive anorexia and weight loss and emphasize that additional work is needed to untangle the relationship among metformin, GDF15 and energy balance.
Publisher: Public Library of Science (PLoS)
Date: 27-04-2017
No related grants have been discovered for Kristine Færch.