Changes in 25(OH) vitamin D levels, leptin levels and ...1 Centre de recherche de l'Institut...
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Changes in 25(OH) vitamin D levels, leptin levels and visceral adipose tissue volume: Results from a lifestyle intervention program in viscerally obese men. Anne Gangloff 1,2,3 (MD, PhD), Jean Bergeron 2 (MD, MSc) Isabelle Lemieux 1 (PhD), Angelo Tremblay 1 (PhD), Paul Poirier 1 (MD, PhD), Natalie Alméras 1 (PhD), Jean-Pierre Després 1 (PhD) 1 Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec, Québec City, Québec, Canada. 2 Lipid Research Centre, Service of Lipidology, Department of Medicine, Université Laval, Centre Hospitalier Universitaire de Québec, Pavilion CHUL, Québec City, Québec, Canada. 3 Endocrinology and Nephrology Unit, CHU de Québec Research Centre, 2705 Boulevard Laurier, Québec City, Canada. Abstract Background/synopsis: Vitamin D deficiency and elevated leptinemia have both been associated with obesity in numerous studies. To date, whether there is an association between vitamin D and leptin levels independent from adiposity remains uncertain. Purpose: To investigate the associations between changes in 25(OH) vitamin D levels, changes in adiposity variables and changes in leptin levels following a 1-year lifestyle intervention program. Methods: Design and Setting: Intervention study (SYNERGIE study) performed on participants recruited from the general community. Participants: Sedentary, abdominally obese and dyslipidemic men (n=113) involved in a 1-year lifestyle modification program. Intervention: Subjects were individually counselled by a kinesiologist and a nutritionist once every 2 weeks during the first 4 months with subsequent monthly visits in order to elicit a 500 kcal daily energy deficit and to increase physical activity/ exercise habits. Main Outcome Measures: Cardiometabolic risk profile and adiposity mapping by computed tomography, to which a plasma vitamin D measurement was added. Results: The 1-year intervention resulted in a 27% increase in plasma 25(OH) vitamin D (from 50±18 nmol/L to 60±18 nmol/L, p<0.0001), a 26% decrease in visceral adipose tissue volume (from 1951±481 cm 3 to 1463±566 cm 3 ) and a 27% decrease in leptin (from 12±8 ng/mL to 9±8 ng/mL). One-year increases in 25(OH)D levels correlated inversely with 1-year changes in leptin levels (r=-0.41, p<0.001). The association remained significant after adjustment for 1-year changes in various adiposity indices: visceral adipose tissue (r=-0.30, p=0.002), subcutaneous adipose tissue (r=-0.35, p=0.0004), total abdominal adipose tissue (r=-0.31, p=0.002) and fat mass (r=-0.31, p=0.001). Conclusions: Changes in 25(OH) vitamin D were independently associated with changes in leptinemia after adjustment for adiposity changes. This finding supports the notion of a possible link between 25(OH)D vitamin D and leptin independent from adiposity. Conclusion Objective Methods Acknowledgements Summary To investigate the associations between changes in 25(OH) vitamin D levels, changes in adiposity variables and changes in leptin levels following a 1-year lifestyle intervention program. Subjects: 113 men between 30 and 65 years, presenting abdominal obesity (waist circumference ≥90 cm), triglyceride levels ≥1.69 mmol/L and/or HDL-cholesterol <1.03 mmol/L were included in a lifestyle intervention. Subjects with type 2 diabetes, body mass index (BMI) values <25 or >40 kg/m 2 , taking medication targeting glucose metabolism, lipid metabolism, or blood pressure management were excluded. Intervention: Subjects were individually counselled by a dietician and a kinesiologist once every 2 weeks during the first 4 months of the intervention with subsequent monthly visits. The goal was to reduce calorie consumption by 500 kcal/day during the first year. The physical activity program aimed to reach 160 min/week of moderate intensity endurance exercise. Diet and fitness assessment: A 3-day dietary record both at the initial visit and at the 1-year follow-up was used to quantify overall nutritional quality. A standardized exercise test was performed to assess cardiorespiratory fitness using the subject's heart rate at a standardized submaximal treadmill workload (3.5 mph, 2% slope). Anthropometry, body composition and adiposity mapping: Height, weight, hip circumference and waist circumference were measured according to standardized procedures. Dual-energy X-ray absorptiometry was used to assess fat mass. VAT, subcutaneous adipose tissue (SAT) and total adipose tissue (TAT) cross-sectional areas were assessed by computed tomography and partial volumes between L2–L3 and L4–L5 were calculated. 25(OH) vitamin D measurement: Plasma samples were collected in EDTA vacutainers at the initial and at the 1-year follow-up visits. The Vitamin D Total assay from Roche was used and measurements were performed in batch on a MODULAR ANALYTICS E170 (Roche). Circulating 25(OH)D levels were adjusted for the season of venipuncture. Leptin and adiponectin measurements: Plasma leptin and adiponectin concentrations (B- Bridge, CA) were determined by ELISA on frozen plasma samples (-80°C). Statistical analysis: All statistical analyses were performed using SAS 9.4. • Vitamin D [25(OH)D] insufficiency and obesity are two prevalent health conditions worldwide. • A high prevalence of 25(OH)D insufficiency has been reported among obese individuals. • Cross-sectional studies have already established a negative association between visceral adipose tissue (VAT) volume and circulating 25(OH)D levels. We have recently reported that the reduction in adiposity, especially VAT reduction, produced by a lifestyle modification program was associated with an increase in circulating vitamin D levels (Gangloff A. et al. Int J Obes 2015, 39; 1638-1643). • A recent meta-analysis investigating the effects of vitamin D supplementation on adipokine levels indicated that increases in 25(OH)D levels following vitamin D supplementation were significantly associated with decreases in leptin levels. No significant effect of vitamin D supplementation on adiponectin and leptin levels was found (Dinca M. et al. Pharmacol Res 2016, 107; 360-371). • To date, no intervention study has investigated whether the relationship between adipose tissue volume loss and increases in circulating 25(OH)D levels in non-vitamin D supplemented men could be mediated, at least in part, by changes in adipokine levels. Background Results • One-year changes in adiposity, 25(OH)D, leptin, adiponectin, steps per day and heart rate at submaximall treadmill workload were all statistically significant and improved between baseline and the 1-year visits (Table 1). • Significant associations were found between changes in circulating 25(OH)D levels and changes in volume of every adipose tissue depot (Table 2). • One-year changes in adipokine levels (leptin and adiponectin) are associated with 1-year changes in adiposity volume variables (Table 3). • One-year changes in 25(OH)D levels were correlated with changes in leptin and adiponectin levels, the association being stronger between 25(OH)D changes and leptin changes (Figures 1 and 2). • The relationship between changes in 25(OH)D levels and changes in leptin levels remained significant after adjusting for changes in adipose tissue volume (Table 4). • However, the relationship between changes in 25(OH)D and changes in adiponectin levels became nonsignificant after control for changes in adipose tissue volume (Table 4). Changes in 25(OH) vitamin D were independently associated with changes in leptinemia after adjustment for adiposity changes. This finding supports the notion of a possible link between 25(OH)D vitamin D and leptin independent from adiposity. This study was supported by the Canadian Institutes of Health Research. Table 1: Characteristics of the sample of 113 men involved in the 1-year lifestyle intervention program Table 2: Correlations between 1-year changes in 25(OH)D and 1-year changes in adiposity variables Table 3: Correlations between 1-year changes in adipokines and 1-year changes in adiposity variables Figure 1: Correlation between changes in leptinemia and changes in 25(OH) vitamin D levels in response to a 1-year lifestyle modification program Figure 2: Correlation between changes in adiponectinemia and changes in 25(OH) vitamin D in response to a 1-year lifestyle modification program Table 4: Partial correlations between 1-year changes in 25(OH)D and 1-year changes in adipokines after adjustment for 1-year changes in adiposity indices 1#year changes in 1#year changes in 25(OH)D r value P value SAT volume "0.27 0.0057 VAT volume "0.30 0.0018 TAT volume "0.33 0.0007 Fat mass "0.28 0.0035 BMI "0.28 0.0026 Waist girth "0.28 0.0032 1#year changes in 1#year changes in r value P value LEPTIN SAT volume 0.49 <0.0001 VAT volume 0.48 <0.0001 TAT volume 0.51 <0.0001 Fat mass 0.55 <0.0001 BMI 0.55 <0.0001 Waist girth 0.49 <0.0001 ADIPONECTIN SAT volume #0.40 <0.0001 VAT volume #0.30 0.0023 TAT volume #0.35 0.0004 Fat mass #0.38 <0.0001 BMI #0.34 0.0003 Waist girth #0.36 0.0002 1"year changes in Adjusted for 1"year changes in 1"year changes in 25(OH)D Partial r value P value Leptin SAT volume "0.35 0.0004 Leptin VAT volume "0.30 0.0019 Leptin TAT volume "0.31 0.0015 Leptin Fat mass "0.31 0.0010 Adiponectin SAT volume 0.12 NS Adiponectin VAT volume 0.12 NS Adiponectin TAT volume 0.12 NS Adiponectin Fat mass 0.11 NS Baseline Post 1 year Absolute changes % changes P value Age (years) 48 ±9 49 ±9 +1.2 ±0.1 +3 <0.0001 Anthropometry Weight (kg) 95.0 ±11.9 88.2 ±12.1 H6.8 ±4.6 H7 <0.0001 BMI (kg/m 2 ) 31.1 ±3.1 28.9 ±3.3 H2.2 ±1.5 H7 <0.0001 Waist circumference (cm) 108.3 ±8.9 99.9 ±10.0 H8.7 ±5.4 H8 <0.0001 Adiposity SAT volume (cm 3 ) 1781 ±639 1454 ±575 H330 ±264 H18 <0.0001 VAT volume (cm 3 ) 1951 ±481 1463 ±566 H497 ±349 H26 <0.0001 TAT volume (cm 3 ) 3723 ±893 2900 ±936 H832 ±560 H23 <0.0001 Fat mass (kg) 29.5 ±7.1 23.5 ±7.7 H6.0 ±3.9 H21 <0.0001 Hormones 25(OH) vitamin D (nmol/L) 50 ±18 60 ±18 +10 ±13 +27 <0.0001 Leptin (ng/mL) 12.0 ±8.1 8.5 ±7.8 H3.5 ±4.1 H27 <0.0001 Adiponectin (ug/mL) 3.8 ±1.5 4.5 ±1.8 +0.8 ±1.1 +26 <0.0001 Lifestyle Daily caloric intake (kcal) 3033 ±627 2439 ±504 H571 ±669 H17 <0.0001 Steps per day 7614 ±2810 9759 ±3198 +2022 ±2791 +37 <0.0001 Heart rate at submaximal treadmill workload (beats/min) 118 ±14 104 ±14 H13 ±11 H11 <0.0001 r=#0.41, p<0.0001 !25 !20 !15 !10 !5 0 5 10 !50 !40 !30 !20 !10 0 10 20 30 40 50 60 1#year changes in lep6n levels (ng/mL) 1#year changes in circula6ng 25(OH) vitamin D (nmol/L) r=0.24, p=0.01 !2 !1 0 1 2 3 4 5 !50 !40 !30 !20 !10 0 10 20 30 40 50 60 1+year changes in adiponec7n levels (ug/mL) 1+year changes in circula7ng 25(OH) vitamin D (nmol/L)
Transcript of Changes in 25(OH) vitamin D levels, leptin levels and ...1 Centre de recherche de l'Institut...
Changes in 25(OH) vitamin D levels, leptin levels and visceral adipose tissue volume: Results from a lifestyle intervention program in viscerally obese men.
Anne Gangloff1,2,3 (MD, PhD), Jean Bergeron2 (MD, MSc) Isabelle Lemieux1 (PhD), Angelo Tremblay1 (PhD), Paul Poirier1 (MD, PhD), Natalie Alméras1 (PhD), Jean-Pierre Després1
(PhD) 1 Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec, Québec City, Québec, Canada.
2 Lipid Research Centre, Service of Lipidology, Department of Medicine, Université Laval, Centre Hospitalier Universitaire de Québec, Pavilion CHUL, Québec City, Québec, Canada. 3 Endocrinology and Nephrology Unit, CHU de Québec Research Centre, 2705 Boulevard Laurier, Québec City, Canada.
Abstract
Background/synopsis: Vitamin D deficiency and elevated leptinemia have both been associated with obesity in numerous studies. To date, whether there is an association between vitamin D and leptin levels independent from adiposity remains uncertain. Purpose: To investigate the associations between changes in 25(OH) vitamin D levels, changes in adiposity variables and changes in leptin levels following a 1-year lifestyle intervention program. Methods: Design and Setting: Intervention study (SYNERGIE study) performed on participants recruited from the general community. Participants: Sedentary, abdominally obese and dyslipidemic men (n=113) involved in a 1-year lifestyle modification program. Intervention: Subjects were individually counselled by a kinesiologist and a nutritionist once every 2 weeks during the first 4 months with subsequent monthly visits in order to elicit a 500 kcal daily energy deficit and to increase physical activity/exercise habits. Main Outcome Measures: Cardiometabolic risk profile and adiposity mapping by computed tomography, to which a plasma vitamin D measurement was added. Results: The 1-year intervention resulted in a 27% increase in plasma 25(OH) vitamin D (from 50±18 nmol/L to 60±18 nmol/L, p<0.0001), a 26% decrease in visceral adipose tissue volume (from 1951±481 cm3 to 1463±566 cm3) and a 27% decrease in leptin (from 12±8 ng/mL to 9±8 ng/mL). One-year increases in 25(OH)D levels correlated inversely with 1-year changes in leptin levels (r=-0.41, p<0.001). The association remained significant after adjustment for 1-year changes in various adiposity indices: visceral adipose tissue (r=-0.30, p=0.002), subcutaneous adipose tissue (r=-0.35, p=0.0004), total abdominal adipose tissue (r=-0.31, p=0.002) and fat mass (r=-0.31, p=0.001). Conclusions: Changes in 25(OH) vitamin D were independently associated with changes in leptinemia after adjustment for adiposity changes. This finding supports the notion of a possible link between 25(OH)D vitamin D and leptin independent from adiposity.
Conclusion
Objective
Methods
Acknowledgements
Summary To investigate the associations between changes in 25(OH) vitamin D levels, changes in adiposity variables and changes in leptin levels following a 1-year lifestyle intervention program.
Subjects: 113 men between 30 and 65 years, presenting abdominal obesity (waist circumference ≥90 cm), triglyceride levels ≥1.69 mmol/L and/or HDL-cholesterol <1.03 mmol/L were included in a lifestyle intervention. Subjects with type 2 diabetes, body mass index (BMI) values <25 or >40 kg/m2, taking medication targeting glucose metabolism, lipid metabolism, or blood pressure management were excluded. Intervention: Subjects were individually counselled by a dietician and a kinesiologist once every 2 weeks during the first 4 months of the intervention with subsequent monthly visits. The goal was to reduce calorie consumption by 500 kcal/day during the first year. The physical activity program aimed to reach 160 min/week of moderate intensity endurance exercise. Diet and fitness assessment: A 3-day dietary record both at the initial visit and at the 1-year follow-up was used to quantify overall nutritional quality. A standardized exercise test was performed to assess cardiorespiratory fitness using the subject's heart rate at a standardized submaximal treadmill workload (3.5 mph, 2% slope). Anthropometry, body composition and adiposity mapping: Height, weight, hip circumference and waist circumference were measured according to standardized procedures. Dual-energy X-ray absorptiometry was used to assess fat mass. VAT, subcutaneous adipose tissue (SAT) and total adipose tissue (TAT) cross-sectional areas were assessed by computed tomography and partial volumes between L2–L3 and L4–L5 were calculated. 25(OH) vitamin D measurement: Plasma samples were collected in EDTA vacutainers at the initial and at the 1-year follow-up visits. The Vitamin D Total assay from Roche was used and measurements were performed in batch on a MODULAR ANALYTICS E170 (Roche). Circulating 25(OH)D levels were adjusted for the season of venipuncture. Leptin and adiponectin measurements: Plasma leptin and adiponectin concentrations (B-Bridge, CA) were determined by ELISA on frozen plasma samples (-80°C). Statistical analysis: All statistical analyses were performed using SAS 9.4.
• Vitamin D [25(OH)D] insufficiency and obesity are two prevalent health conditions worldwide.
• A high prevalence of 25(OH)D insufficiency has been reported among obese individuals.
• Cross-sectional studies have already established a negative association between visceral adipose tissue (VAT) volume and circulating 25(OH)D levels. We have recently reported that the reduction in adiposity, especially VAT reduction, produced by a lifestyle modification program was associated with an increase in circulating vitamin D levels (Gangloff A. et al. Int J Obes 2015, 39; 1638-1643).
• A recent meta-analysis investigating the effects of vitamin D supplementation on adipokine levels indicated that increases in 25(OH)D levels following vitamin D supplementation were significantly associated with decreases in leptin levels. No significant effect of vitamin D supplementation on adiponectin and leptin levels was found (Dinca M. et al. Pharmacol Res 2016, 107; 360-371).
• To date, no intervention study has investigated whether the relationship between adipose tissue volume loss and increases in circulating 25(OH)D levels in non-vitamin D supplemented men could be mediated, at least in part, by changes in adipokine levels.
Background Results
• One-year changes in adiposity, 25(OH)D, leptin, adiponectin, steps per day and heart rate at submaximall treadmill workload were all statistically significant and improved between baseline and the 1-year visits (Table 1).
• Significant associations were found between changes in circulating 25(OH)D levels and changes in volume of every adipose tissue depot (Table 2).
• One-year changes in adipokine levels (leptin and adiponectin) are associated with 1-year changes in adiposity volume variables (Table 3).
• One-year changes in 25(OH)D levels were correlated with changes in leptin and adiponectin levels, the association being stronger between 25(OH)D changes and leptin changes (Figures 1 and 2).
• The relationship between changes in 25(OH)D levels and changes in leptin levels remained significant after adjusting for changes in adipose tissue volume (Table 4).
• However, the relationship between changes in 25(OH)D and changes in adiponectin levels became nonsignificant after control for changes in adipose tissue volume (Table 4).
Changes in 25(OH) vitamin D were independently associated with changes in leptinemia after adjustment for adiposity changes. This finding supports the notion of a possible link between 25(OH)D vitamin D and leptin independent from adiposity.
This study was supported by the Canadian Institutes of Health Research.
Table 1: Characteristics of the sample of 113 men involved in the 1-year lifestyle intervention program
Table 2: Correlations between 1-year changes in 25(OH)D and 1-year changes in adiposity variables
Table 3: Correlations between 1-year changes in adipokines and 1-year changes in adiposity variables
Figure 1: Correlation between changes in leptinemia and changes in 25(OH) vitamin D levels in response to a 1-year lifestyle modification program
Figure 2: Correlation between changes in adiponectinemia and changes in 25(OH) vitamin D in response to a 1-year lifestyle modification program
Table 4: Partial correlations between 1-year changes in 25(OH)D and 1-year changes in adipokines after adjustment for 1-year changes in adiposity indices
!1#year!changes!in! 1#year!changes!in!25(OH)D!!r!value!
!P!value!
! ! !SAT!volume!! "0.27! 0.0057!VAT!volume! "0.30! 0.0018!TAT!volume! "0.33! 0.0007!Fat!mass! "0.28! 0.0035!BMI! "0.28! 0.0026!Waist!girth! "0.28! 0.0032!!
!1#year!changes!in! 1#year!changes!in!!r!value!
!P!value!
! ! !!! LEPTIN! !!SAT!volume!! 0.49! <0.0001!VAT!volume! 0.48! <0.0001!TAT!volume! 0.51! <0.0001!Fat!mass! 0.55! <0.0001!BMI! 0.55! <0.0001!Waist!girth! 0.49! <0.0001!!! !! !!!! ADIPONECTIN! !!SAT!volume!! #0.40! <0.0001!VAT!volume! #0.30! 0.0023!TAT!volume! #0.35! 0.0004!Fat!mass! #0.38! <0.0001!BMI! #0.34! 0.0003!Waist!girth! #0.36! 0.0002!!
1"year'changes'in' Adjusted'for'1"year'changes'in'
1"year'changes'in'25(OH)D'Partial'r'value'
P'value'
' ' ' 'Leptin' SAT'volume' "0.35' 0.0004'Leptin' VAT'volume' "0.30' 0.0019'Leptin' TAT'volume' "0.31' 0.0015'Leptin' Fat'mass' "0.31' 0.0010''' '' ' ''Adiponectin' SAT'volume' 0.12' NS'Adiponectin' VAT'volume' 0.12' NS'Adiponectin' TAT'volume' 0.12' NS'Adiponectin' Fat'mass' 0.11' NS'!
!! Baseline! Post!1!year!! Absolute!
changes!
%!changes! !P!value!
!!
! ! ! ! ! !
Age!(years)! 48!±9! 49!±9! +1.2!±0.1! +3! <0.0001!
!! !! !! !! ! !!
Anthropometry! !! !! !! ! !!
Weight!(kg)! 95.0!±11.9! 88.2!±12.1! H6.8!±4.6! H7! <0.0001!
BMI!(kg/m2)! 31.1!±3.1! 28.9!±3.3! H2.2!±1.5! H7! <0.0001!
Waist!circumference!(cm)! 108.3!±8.9! 99.9!±10.0! H8.7!±5.4! H8! <0.0001!
!! !! !! !! ! !!
Adiposity! !! !! !! ! !!
SAT!volume!(cm3)! 1781!±639! 1454!±575! H330!±264! H18! <0.0001!
VAT!volume!(cm3)! 1951!±481! 1463!±566! H497!±349! H26! <0.0001!
TAT!volume!(cm3)! 3723!±893! 2900!±936! H832!±560! H23! <0.0001!
Fat!mass!(kg)! 29.5!±7.1! 23.5!±7.7! H6.0!±3.9! H21! <0.0001!
!! !! !! !! ! !!
Hormones! !! !! !! ! !!
25(OH)!vitamin!D!(nmol/L)! 50!±18! 60!±18! +10!±13! +27! <0.0001!
Leptin!(ng/mL)! 12.0!±8.1! 8.5!±7.8! H3.5!±4.1! H27! <0.0001!
Adiponectin!(ug/mL)! 3.8!±1.5! 4.5!±1.8! +0.8!±1.1! +26! <0.0001!
!! !! !! !! ! !!
Lifestyle! !! !! !! ! !!
Daily!caloric!intake!(kcal)! 3033!±627! 2439!±504! H571!±669! H17! <0.0001!
Steps!per!day! 7614!±2810! 9759!±3198! +2022!±2791! +37! <0.0001!
Heart!rate!at!submaximal!
treadmill!workload!
(beats/min)!
118!±14! 104!±14! H13!±11! H11! <0.0001!
!
r=#0.41,)p<0.0001)
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