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Aging and disease    2017, Vol. 8 Issue (2) : 240-249     DOI: 10.14336/AD.2016.0819
Original Article |
Serum Leptin Concentration is Associated with Incident Frailty in Older Adults
Lana Alberto1,2, Valdés-Bécares Ana1, Buño Antonio3, Rodríguez-Artalejo Fernando2, Lopez-Garcia Esther2
1Department of Medicine, Preventive Medicine and Public Health Area, School of Medicine and Health Sciences, Universidad de Oviedo, Oviedo, Spain
2Department of Preventive Medicine and Public Health, School of Medicine, Universidad Autónoma de Madrid, IdiPaz (Instituto de Investigación Sanitaria Hospital Universitario La Paz), and CIBERESP (CIBER of Epidemiology and Public Health), Madrid, Spain
3Department of Laboratory Medicine, Hospital University La Paz, Madrid, Spain
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Obesity has been associated with higher risk of frailty in older adults, but the pathophysiological mechanisms are unclear. No previous study has examined the association between leptin, an adipokine, and the risk of frailty in older adults, and whether this association could be explained by insulin resistance or chronic inflammation. Data were taken from 1,573 individuals without diabetes mellitus, aged ≥60 years, from the Seniors-ENRICA cohort. In 2008-2010, leptin, the homeostasis model assessment of insulin resistance (HOMA-IR) and C-reactive protein (CRP) were measured. Study participants were followed-up through 2012 to assess incident frailty, defined as at least two of the following Fried criteria: exhaustion, weakness, low physical activity, and slow walking speed. Analyses were performed with logistic regression and adjusted for the main confounders. Over a median follow-up of 3.5 years, 280 cases of incident frailty were identified. Compared to individuals in the lowest tertile of serum leptin, those in the highest tertile showed an increased risk of frailty (odds ratio [OR]: 2.12; 95% confidence interval [CI]: 1.47-3.06; p-trend <0.001). Further adjustment for the percentage of body fat led to an OR of 1.69 (95% CI: 1.11-2.61; p-trend=0.01). After additional adjustment for HOMA-IR and CRP, the OR for frailty was 1.59 (95% CI: 1.01-2.52; p-trend=0.04). Results did not vary according to sex, abdominal obesity or the percentage of body fat. Being in the highest versus lowest tertile of leptin was associated with increased risk of exhaustion (OR: 2.16; 95% CI: 1.32-3.55; p-trend=0.001) and muscle weakness (OR: 1.77; 95% CI: 1.25-2.51; p-trend=0.001), in the analyses adjusted for potential confounders and body fat. Higher leptin concentration was associated with greater risk of frailty in older adults. This association was only modestly explained by insulin resistance and chronic inflammation, as measured by CRP.

Keywords older adults      leptin      biological markers      obesity      insulin resistance     
Corresponding Authors: Lana Alberto   
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These authors contributed equally to this work

Issue Date: 01 April 2017
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Lana Alberto
Valdés-Bécares Ana
Buño Antonio
Rodríguez-Artalejo Fernando
Lopez-Garcia Esther
Cite this article:   
Lana Alberto,Valdés-Bécares Ana,Buño Antonio, et al. Serum Leptin Concentration is Associated with Incident Frailty in Older Adults[J]. Aging and disease, 2017, 8(2): 240-249.
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Leptin concentration
Tertile 1
Tertile 2Tertile 3
Participants, n528531514
Age, y68.4 (6.6)68.0 (6.0)68.9 (6.3)0.17
Men, %46.646.346.90.93
University education, %
Current smoker, %
Moderate drinker, %56.359.759.10.34
Leisure-time physical activity, MET-h/wk24.2 (15.8)22.6 (14.9)19.3 (14.3)<0.001
TV watching, h/d2.2 (1.3)2.5 (1.4)2.8 (1.7)<0.001
Energy, kcal/d2,040 (556)2,051 (561)2,014 (567)0.46
Trichopoulou index score4.7 (1.5)4.5 (1.5)4.4 (1.6)0.02
Waist circumference, cm89.2 (10.5)95.8 (9.1)104.2 (10.6)<0.001
Body fat, %33.9 (6.5)36.8 (6.5)40.5 (7.2)<0.001
Morbidity, %
 Cardiovascular disease4.
 Chronic lung disease4.
 Osteomuscular disease40.749.252.3<0.001
Independent in IADL, %91.390.288.30.02
Optimal self-rated health, %78.871.062.8<0.001
HOMA-IR1.4 (1.0)2.0 (1.1)3.0 (2.0)<0.001
CRP, mg/L0.25 (0.4)0.39 (0.9)0.43 (0.7)<0.001
Table 1  Characteristics of study participants according to sex-specific tertilesa of serum leptin concentration. (N=1,573)
Leptin concentration
Tertile 1
Tertile 2Tertile 3
 Participants, n528531514
 Frailty cases6582133
 Model 1a1.001.38 (0.96-1.99)2.57 (1.83-3.60)<0.001
 Model 2b1.001.27 (0.87-1.87)2.12 (1.47-3.06)<0.001
 Model 3b1.001.19 (0.79-1.78)1.69 (1.11-2.61)0.01
 Model 4b1.001.14 (0.75-1.72)1.59 (1.01-2.52)0.04
Sensitivity analyses
Frailty including weight loss
 Participants, n528531514
 Frailty cases142358
 Model 1a1.001.89 (0.94-3.80)5.26 (2.83-9.80)<0.001
 Model 2b1.001.66 (0.80-3.46)4.25 (2.18-8.29)<0.001
 Model 3b1.001.64 (0.76-3.52)4.09 (1.90-8.79)<0.001
 Model 4b1.001.41 (0.65-3.08)2.95 (1.29-6.72)0.005
Defining weakness as lowest quintile of grip strength in our sample
 Participants, n528531514
 Frailty cases5560102
 Model 1a1.001.15 (0.77-1.72)2.25 (1.55-3.26)<0.001
 Model 2b1.001.04 (0.67-1.59)1.78 (1.19-1.66)0.003
 Model 3b1.001.09 (0.69-1.72)1.78 (1.10-2.88)0.01
 Model 4b1.001.05 (0.66-1.68)1.67 (1.01-2.80)0.04
Participants independent in IADL
 Participants, n478474448
 Frailty cases5261104
 Model 1a1.001.35 (0.90-2.02)2.60 (1.79-3.77)<0.001
 Model 2b1.001.22 (0.80-1.88)2.13 (1.43-3.19)<0.001
 Model 3b1.001.06 (0.68-1.65)1.58 (0.99-2.52)0.04
 Model 4b1.001.03 (0.65-1.62)1.50 (0.91-2.49)0.09
Participants with optimal self-rated health
 Participants, n444357
 Frailty cases413372320
 Model 1a1.001.20 (0.76-1.90)1.86 (1.20-2.89)0.006
 Model 2b1.001.15 (0.71-1.88)1.66 (1.04-2.65)0.03
 Model 3b1.001.03 (0.62-1.71)1.32 (0.76-2.28)0.32
 Model 4b1.001.03 (0.61-1.73)1.33 (0.73-2.41)0.35
Participants without diagnosed chronic disease
 Participants, n284229203
 Frailty cases231931
 Model 1a1.001.12 (0.58-2.15)2.20 (1.22-3.98)0.009
 Model 2b1.001.21 (0.61-2.40)2.17 (1.15-4.12)0.02
 Model 3b1.001.05 (0.52-2.12)1.53 (0.73-3.21)0.26
 Model 4b1.001.04(0.51-2.15)1.51 (0.68-3.35)0.32
Participants who spent < 2 h/d watching TV
 Participants, n318219235
 Frailty cases353149
 Model 1a1.001.43 (0.87-2.35)2.23 (1.37-3.63)0.001
 Model 2b1.001.30 (0.76-2.24)1.96 (1.14-3.37)0.01
 Model 3b1.001.11 (0.62-1.97)1.45 (0.77-2.75)0.24
 Model 4b1.001.05 (0.58-1.91)1.33 (0.66-2.66)0.40
Participants whose diet had a Trichopoulou index ≥ 5
 Participants, n297277245
 Frailty cases364463
 Model 1a1.001.57 (0.96-2.58)2.61 (1.63-4.20)<0.001
 Model 2b1.001.54 (0.90-2.65)2.36 (1.40-3.98)0.001
 Model 3b1.001.27 (0.72-2.26)1.73 (0.93-3.19)0.08
 Model 4b1.001.18 (0.65-2.12)1.57 (0.81-3.05)0.18
Table 2  Odds ratios (95% confidence interval) for the association between serum concentration of leptin and risk of frailty, in the total study sample and according to characteristics of study participants. (N=1,573)
Leptin concentration
Tertile 1
Tertile 2Tertile 3
Abdominal obesity
 Participants, n287288285
 Frailty cases466290
 Model 1a1.001.15 (0.71-1.86)1.94 (1.15-3.26)0.006
 Model 2b1.001.09 (0.64-1.85)1.56 (0.88-2.77)0.09
No abdominal obesity
 Participants, n238238237
 Frailty cases251938
 Model 1a1.000.73 (0.38-1.43)1.74 (0.85-3.56)0.120.12
 Model 2b1.000.69 (0.33-1.41)1.72 (0.79-3.72)0.150.16
Body fat % ≥ median in study sample
 Participants, n262263262
 Frailty cases425886
 Model 1a1.001.17 (0.64-2.13)1.88 (1.08-3.25)0.001
 Model 2b1.001.12 (0.59-2.13)1.69 (0.93-3.06)0.02
Body fat % < median in study sample
 Participants, n265260261
 Frailty cases252936
 Model 1a1.001.37 (0.83-2.28)2.14 (1.09-4.20)0.020.47
 Model 2b1.001.38 (0.79-2.40)2.03 (0.96-4.29)0.050.56
Table 3  Odds ratios (95% confidence interval) for the association between serum concentration of leptin and risk of frailty, by abdominal obesity and body fat (N=1,573).
Leptin concentration
Tertile 1
Tertile 2Tertile 3
Participants, n528531514
 Criterion present495596
 Model 1a1.001.16 (0.77-1.76)2.29 (1.57-3.34)<0.001
 Model 2b1.001.06 (0.68-1.65)2.05 (1.36-3.10)<0.001
 Model 3c1.001.12 (0.70-1.79)2.16 (1.32-3.55)0.001
 Model 4d1.001.14 (0.71-1.84)2.24 (1.32-3.80)0.002
Low physical activity
 Criterion present6771105
 Model 1a1.001.06 (0.74-1.52)1.77 (1.26-2.47)0.001
 Model 2b1.000.97 (0.64-1.42)1.40 (0.97-2.01)0.06
 Model 3c1.000.94 (0.63-1.40)1.18 (0.77-1.81)0.42
 Model 4d1.000.91 (0.60-1.37)1.11 (0.70-1.77)0.61
Slow walking speed
 Criterion present646885
 Model 1a1.001.10 (0.76-1.15)1.41 (0.99-2.01)0.06
 Model 2b1.001.08 (0.74-1.57)1.30 (0.90-1.89)0.16
 Model 3c1.001.14 (0.77-1.69)1.48 (0.96-2.29)0.08
 Model 4d1.001.01 (0.67-1.52)1.19 (0.74-1.92)0.46
Muscle weakness
 Criterion present132149230
 Model 1a1.001.26 (0.94-1.69)2.61 (1.97-3.46)<0.001
 Model 2b1.001.17 (0.86-1.58)2.35 (1.75-3.17)<0.001
 Model 3c1.001.05 (0.76-1.43)1.77 (1.25-2.51)0.001
 Model 4d1.001.01 (0.73-1.40)1.68 (1.15-2.44)0.005
Weight loss
 Criterion present313243
 Model 1a1.001.04 (0.62-1.73)1.45 (0.90-2.35)0.12
 Model 2b1.001.02 (0.61-1-73)1.40 (0.84-2.33)0.18
 Model 3c1.000.98 (0.57-1.69)1.34 (0.74-2.42)0.32
 Model 4d1.000.97 (0.55-1.67)1.25 (0.66-2.35)0.49
Table 4  Odds ratios (95% confidence interval) for the association between plasma concentration of leptin and risk of each frailty criterion. (N=1,573)
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