Background and Aim: Inflammatory and methylation imbalances occur in patients with type 2 diabetes mellitus (T2DM). The aim of the present study was to analyze the effect of acute resistance exercise on the inflammatory profile and on DNA methylation of elderly patients with T2DM using metformin. Methods: For this purpose, we enrolled 22 male and female older adults (68.2 ± 5.3 years), of whom 13 had controlled T2DM (D) under metformin use and 9 were nondiabetics (ND). All subjects underwent a neuromuscular circuit (8 exercises in 40 min, with each exercise performed in 3 sets of 40 s each and a 20-s interval between repetitions). Results: The main results indicated a significant difference between groups for baseline interleukin (IL)-10, with a higher concentration in the D group compared to the ND group (p = 0.019). An increase in IL-6 concentration after intervention was observed in group D (p = 0.035). No effect was observed in total DNA methylation within or between groups. Conclusions: The resistance training protocol applied in this study modulates the IL-10 and IL-6 concentrations in elderly people with T2DM and under metformin use, possibly as a result of physiological adaptations, with no effect on nondiabetic elderly. No effects on absolute levels of DNA methylation were observed.

1.
Scott
D
,
Seibel
M
,
Cumming
R
,
Naganathan
V
,
Blyth
F
,
Le Couteur
DG
, et al
Sarcopenic Obesity and Its Temporal Associations With Changes in Bone Mineral Density, Incident Falls, and Fractures in Older Men: The Concord Health and Ageing in Men Project
.
J Bone Miner Res
.
2017
Mar
;
32
(
3
):
575
83
.
[PubMed]
0884-0431
2.
Megale
RZ
,
Ferreira
ML
,
Ferreira
PH
,
Naganathan
V
,
Cumming
R
,
Hirani
V
, et al
Association between pain and the frailty phenotype in older men: longitudinal results from the Concord Health and Ageing in Men Project (CHAMP)
.
Age Ageing
.
2018
May
;
47
(
3
):
381
7
.
[PubMed]
0002-0729
3.
Ryan
DJ
,
Stebbings
GK
,
Onambele
GL
.
The emergence of sedentary behaviour physiology and its effects on the cardiometabolic profile in young and older adults
.
Age (Dordr)
.
2015
Oct
;
37
(
5
):
89
.
[PubMed]
2452-0756
4.
Nascimento
CM
,
Mambrini
JV
,
de Oliveira
CM
,
Giacomin
KC
,
Peixoto
SV
.
Diabetes, hypertension and mobility among Brazilian older adults: findings from the Brazilian National Household Sample Survey (1998, 2003 and 2008)
.
BMC Public Health
.
2015
Jun
;
15
(
1
):
591
.
[PubMed]
1471-2458
5.
American Diabetes Association
.
Diagnosis and classification of diabetes mellitus
.
Diab Ca
.
2010
;
33
Suppl1
:
62
9
.
6.
Zheng
Y
,
Ley
SH
,
Hu
FB
.
Global aetiology and epidemiology of type 2 diabetes mellitus and its complications
.
Nat Rev Endocrinol
.
2018
Feb
;
14
(
2
):
88
98
.
[PubMed]
1759-5029
7.
Aumueller
E
,
Remely
M
,
Baeck
H
,
Hippe
B
,
Brath
H
,
Haslberger
AG
.
Interleukin-6 CpG Methylation and Body Weight Correlate Differently in Type 2 Diabetes Patients Compared to Obese and Lean Controls
.
J Nutrigenet Nutrigenomics
.
2015
;
8
(
1
):
26
35
.
[PubMed]
1661-6499
8.
Rodrigues
KF
,
Pietrani
NT
,
Bosco
AA
,
Campos
FM
,
Sandrim
VC
,
Gomes
KB
.
IL-6, TNF-α, and IL-10 levels/polymorphisms and their association with type 2 diabetes mellitus and obesity in Brazilian individuals
.
Arch Endocrinol Metab
.
2017
Sep-Oct
;
61
(
5
):
438
46
.
[PubMed]
2359-3997
9.
Boraska
V
,
Rayner
NW
,
Groves
CJ
,
Frayling
TM
,
Diakite
M
,
Rockett
KA
, et al
Large-scale association analysis of TNF/LTA gene region polymorphisms in type 2 diabetes
.
BMC Med Genet
.
2010
May
;
11
(
1
):
69
.
[PubMed]
1471-2350
10.
Erdogan
M
,
Cetinkalp
S
,
Ozgen
AG
,
Saygili
F
,
Berdeli
A
,
Yilmaz
C
.
Interleukin-10 (-1082G/A) gene polymorphism in patients with type 2 diabetes with and without nephropathy
.
Genet Test Mol Biomarkers
.
2012
Feb
;
16
(
2
):
91
4
.
[PubMed]
1945-0265
11.
Curti
ML
,
Pires
MM
,
Barros
CR
,
Siqueira-Catania
A
,
Rogero
MM
,
Ferreira
SR
.
Associations of the TNF-alpha -308 G/A, IL6 -174 G/C and AdipoQ 45 T/G polymorphisms with inflammatory and metabolic responses to lifestyle intervention in Brazilians at high cardiometabolic risk
.
Diabetol Metab Syndr
.
2012
Nov
;
4
(
1
):
49
.
[PubMed]
1758-5996
12.
Tang
L
,
Ye
H
,
Hong
Q
,
Wang
L
,
Wang
Q
,
Wang
H
, et al
Elevated CpG island methylation of GCK gene predicts the risk of type 2 diabetes in Chinese males
.
Gene
.
2014
Sep
;
547
(
2
):
329
33
.
[PubMed]
0378-1119
13.
McKay
JA
,
Mathers
JC
.
Diet induced epigenetic changes and their implications for health
.
Acta Physiol (Oxf)
.
2011
Jun
;
202
(
2
):
103
18
.
[PubMed]
1748-1708
14.
Jeon
JP
,
Koh
IU
,
Choi
NH
,
Kim
BJ
,
Han
BG
,
Lee
S
.
Differential DNA methylation of MSI2 and its correlation with diabetic traits
.
PLoS One
.
2017
May
;
12
(
5
):
e0177406
.
[PubMed]
1932-6203
15.
Yang
BT
,
Dayeh
TA
,
Volkov
PA
,
Kirkpatrick
CL
,
Malmgren
S
,
Jing
X
, et al
Increased DNA methylation and decreased expression of PDX-1 in pancreatic islets from patients with type 2 diabetes
.
Mol Endocrinol
.
2012
Jul
;
26
(
7
):
1203
12
.
[PubMed]
0888-8809
16.
Petersen
AK
,
Zeilinger
S
,
Kastenmüller
G
,
Römisch-Margl
W
,
Brugger
M
,
Peters
A
, et al
Epigenetics meets metabolomics: an epigenome-wide association study with blood serum metabolic traits
.
Hum Mol Genet
.
2014
Jan
;
23
(
2
):
534
45
.
[PubMed]
0964-6906
17.
Nilsson
E
,
Jansson
PA
,
Perfilyev
A
,
Volkov
P
,
Pedersen
M
,
Svensson
MK
, et al
Altered DNA methylation and differential expression of genes influencing metabolism and inflammation in adipose tissue from subjects with type 2 diabetes
.
Diabetes
.
2014
Sep
;
63
(
9
):
2962
76
.
[PubMed]
0012-1797
18.
Ribel-Madsen
R
,
Fraga
MF
,
Jacobsen
S
,
Bork-Jensen
J
,
Lara
E
,
Calvanese
V
, et al
Genome-wide analysis of DNA methylation differences in muscle and fat from monozygotic twins discordant for type 2 diabetes
.
PLoS One
.
2012
;
7
(
12
):
e51302
.
[PubMed]
1932-6203
19.
Dayeh
T
,
Volkov
P
,
Salö
S
,
Hall
E
,
Nilsson
E
,
Olsson
AH
, et al
Genome-wide DNA methylation analysis of human pancreatic islets from type 2 diabetic and non-diabetic donors identifies candidate genes that influence insulin secretion
.
PLoS Genet
.
2014
Mar
;
10
(
3
):
e1004160
.
[PubMed]
1553-7390
20.
Shinozaki
G
,
Braun
PR
,
Hing
BW
,
Ratanatharathorn
A
,
Klisares
MJ
,
Duncan
GN
, et al
Epigenetics of Delirium and Aging: Potential Role of DNA Methylation Change on Cytokine Genes in Glia and Blood Along With Aging
.
Front Aging Neurosci
.
2018
Oct
;
10
:
311
.
[PubMed]
1663-4365
21.
Foran
E
,
Garrity-Park
MM
,
Mureau
C
,
Newell
J
,
Smyrk
TC
,
Limburg
PJ
, et al
Upregulation of DNA methyltransferase-mediated gene silencing, anchorage-independent growth, and migration of colon cancer cells by interleukin-6
.
Mol Cancer Res
.
2010
Apr
;
8
(
4
):
471
81
.
[PubMed]
1541-7786
22.
Horsburgh
S
,
Robson-Ansley
P
,
Adams
R
,
Smith
C
.
Exercise and inflammation-related epigenetic modifications: focus on DNA methylation
.
Exerc Immunol Rev
.
2015
;
21
:
26
41
.
[PubMed]
1077-5552
23.
Hodge
DR
,
Xiao
W
,
Clausen
PA
,
Heidecker
G
,
Szyf
M
,
Farrar
WL
.
Interleukin-6 regulation of the human DNA methyltransferase (HDNMT) gene in human erythroleukemia cells
.
J Biol Chem
.
2001
Oct
;
276
(
43
):
39508
11
.
[PubMed]
0021-9258
24.
Balducci
S
,
Sacchetti
M
,
Haxhi
J
,
Orlando
G
,
D’Errico
V
,
Fallucca
S
, et al
Physical exercise as therapy for type 2 diabetes mellitus
.
Diabetes Metab Res Rev
.
2014
Mar
;
30
(
S1
Suppl 1
):
13
23
.
[PubMed]
1520-7552
25.
Hundal
RS
,
Krssak
M
,
Dufour
S
,
Laurent
D
,
Lebon
V
,
Chandramouli
V
, et al
Mechanism by which metformin reduces glucose production in type 2 diabetes
.
Diabetes
.
2000
Dec
;
49
(
12
):
2063
9
.
[PubMed]
0012-1797
26.
Bridgeman
SC
,
Ellison
GC
,
Melton
PE
,
Newsholme
P
,
Mamotte
CD
.
Epigenetic effects of metformin: from molecular mechanisms to clinical implications
.
Diabetes Obes Metab
.
2018
Jul
;
20
(
7
):
1553
62
.
[PubMed]
1462-8902
27.
Elbere
I
,
Silamikelis
I
,
Ustinova
M
,
Kalnina
I
,
Zaharenko
L
,
Peculis
R
, et al
Significantly altered peripheral blood cell DNA methylation profile as a result of immediate effect of metformin use in healthy individuals
.
Clin Epigenetics
.
2018
Dec
;
10
(
1
):
156
.
[PubMed]
1868-7075
28.
Cuyàs
E
,
Fernández-Arroyo
S
,
Verdura
S
,
García
RA
,
Stursa
J
,
Werner
L
, et al
Metformin regulates global DNA methylation via mitochondrial one-carbon metabolism
.
Oncogene
.
2018
Feb
;
37
(
7
):
963
70
.
[PubMed]
0950-9232
29.
Zhong
T
,
Men
Y
,
Lu
L
,
Geng
T
,
Zhou
J
,
Mitsuhashi
A
, et al
Metformin alters DNA methylation genome-wide via the H19/SAHH axis
.
Oncogene
.
2017
Apr
;
36
(
17
):
2345
54
.
[PubMed]
0950-9232
30.
Lee
JH
,
Lee
R
,
Hwang
MH
,
Hamilton
MT
,
Park
Y
.
The effects of exercise on vascular endothelial function in type 2 diabetes: a systematic review and meta-analysis
.
Diabetol Metab Syndr
.
2018
Mar
;
10
(
1
):
15
.
[PubMed]
1758-5996
31.
Tan
S
,
Du
P
,
Zhao
W
,
Pang
J
,
Wang
J
.
Exercise Training at Maximal Fat Oxidation Intensity for Older Women with Type 2 Diabetes
.
Int J Sports Med
.
2018
May
;
39
(
5
):
374
81
.
[PubMed]
0172-4622
32.
Morais Junior
GS
,
Souza
VC
,
Machado-Silva
W
,
Henriques
AD
,
Melo Alves
A
,
Barbosa Morais
D
, et al
Acute strength training promotes responses in whole blood circulating levels of miR-146a among older adults with type 2 diabetes mellitus
.
Clin Interv Aging
.
2017
Sep
;
12
:
1443
50
.
[PubMed]
1176-9092
33.
World Health Organization
.
Physical status: the use and interpretation of anthropometry
.
Geneva World Health Organization
;
1995
. pp.
1
452
.
34.
World Health Organization
.
Global recommendations on physical activity for health
.
Geneva
:
World Health Organization
;
2010
. p.
60
.
35.
Romero-Arenas
S
,
Martínez-Pascual
M
,
Alcaraz
PE
.
Impact of resistance circuit training on neuromuscular, cardiorespiratory and body composition adaptations in the elderly
.
Aging Dis
.
2013
Oct
;
4
(
5
):
256
63
.
[PubMed]
2152-5250
36.
Hu
FB
,
Meigs
JB
,
Li
TY
,
Rifai
N
,
Manson
JE
.
Inflammatory markers and risk of developing type 2 diabetes in women
.
Diabetes
.
2004
Mar
;
53
(
3
):
693
700
.
[PubMed]
0012-1797
37.
Hotamisligil
GS
.
Inflammation and metabolic disorders
.
Nature
.
2006
Dec
;
444
(
7121
):
860
7
.
[PubMed]
0028-0836
38.
Borowska
M
,
Dworacka
M
,
Wesołowska
A
,
Winiarska
H
,
Krzyżagórska
E
,
Dworacki
G
.
The Impact of Pharmacotherapy of Type 2 Diabetes Mellitus on IL-1β, IL-6 and IL-10 Secretion
.
Pharmacology
.
2016
;
97
(
3-4
):
189
94
.
[PubMed]
0031-7012
39.
Ostrowski
K
,
Rohde
T
,
Asp
S
,
Schjerling
P
,
Pedersen
BK
.
Pro- and anti-inflammatory cytokine balance in strenuous exercise in humans
.
J Physiol
.
1999
Feb
;
515
(
Pt 1
):
287
91
.
[PubMed]
0022-3751
40.
Ostrowski
K
,
Schjerling
P
,
Pedersen
BK
.
Physical activity and plasma interleukin-6 in humans—effect of intensity of exercise
.
Eur J Appl Physiol
.
2000
Dec
;
83
(
6
):
512
5
.
[PubMed]
1439-6319
41.
Petersen
AM
,
Pedersen
BK
.
The anti-inflammatory effect of exercise
.
J Appl Physiol (1985)
.
2005
Apr
;
98
(
4
):
1154
62
.
[PubMed]
8750-7587
42.
Pedersen
BK
,
Steensberg
A
,
Fischer
C
,
Keller
C
,
Keller
P
,
Plomgaard
P
, et al
The metabolic role of IL-6 produced during exercise: is IL-6 an exercise factor?
Proc Nutr Soc
.
2004
May
;
63
(
2
):
263
7
.
[PubMed]
0029-6651
43.
Broholm
C
,
Laye
MJ
,
Brandt
C
,
Vadalasetty
R
,
Pilegaard
H
,
Pedersen
BK
, et al
LIF is a contraction-induced myokine stimulating human myocyte proliferation
.
J Appl Physiol (1985)
.
2011
Jul
;
111
(
1
):
251
9
.
[PubMed]
1522-1601
44.
Pedersen
BK
,
Febbraio
MA
.
Muscles, exercise and obesity: skeletal muscle as a secretory organ
.
Nat Rev Endocrinol
.
2012
Apr
;
8
(
8
):
457
65
.
[PubMed]
1759-5029
45.
Pedersen
BK
,
Febbraio
MA
.
Muscle as an endocrine organ: focus on muscle-derived interleukin-6
.
Physiol Rev
.
2008
Oct
;
88
(
4
):
1379
406
.
[PubMed]
0031-9333
46.
Muñoz-Cánoves
P
,
Scheele
C
,
Pedersen
BK
,
Serrano
AL
.
Interleukin-6 myokine signaling in skeletal muscle: a double-edged sword?
FEBS J
.
2013
Sep
;
280
(
17
):
4131
48
.
[PubMed]
1742-464X
47.
Intine
RV
,
Sarras
MP
 Jr
.
Metabolic memory and chronic diabetes complications: potential role for epigenetic mechanisms
.
Curr Diab Rep
.
2012
Oct
;
12
(
5
):
551
9
.
[PubMed]
1534-4827
48.
Yu
Y
,
Mingjiao
W
,
Yang
X
,
Sui
M
,
Zhang
T
,
Liang
J
, et al
Association between DNA methylation of SORL1 5′-flanking region and mild cognitive impairment in type 2 diabetes mellitus
.
Ann Endocrinol (Paris)
.
2016
Dec
;
77
(
6
):
625
32
.
[PubMed]
0003-4266
49.
Nitert
MD
,
Dayeh
T
,
Volkov
P
,
Elgzyri
T
,
Hall
E
,
Nilsson
E
, et al
Impact of an exercise intervention on DNA methylation in skeletal muscle from first-degree relatives of patients with type 2 diabetes
.
Diabetes
.
2012
Dec
;
61
(
12
):
3322
32
.
[PubMed]
0012-1797
50.
Rönn
T
,
Ling
C
.
Effect of exercise on DNA methylation and metabolism in human adipose tissue and skeletal muscle
.
Epigenomics
.
2013
Dec
;
5
(
6
):
603
5
.
[PubMed]
1750-1911
51.
Rönn
T
,
Ling
C
.
DNA methylation as a diagnostic and therapeutic target in the battle against Type 2 diabetes
.
Epigenomics
.
2015
;
7
(
3
):
451
60
.
[PubMed]
1750-1911
52.
Bortolon
PC
,
de Medeiros
EF
,
Naves
JO
,
Karnikowski
MG
,
Nóbrega
OT
.
[Analysis of the self-medication pattern among Brazilian elderly women]
.
Cien Saude Colet
.
2008
Jul-Aug
;
13
(
4
):
1219
26
.
[PubMed]
1413-8123
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.