Aims: This study aimed to explore the new role of telomere length (TL) in the novel classification of type 2 diabetes mellitus (T2DM) patients driven by cluster analysis. Materials and Methods: A total of 541 T2DM patients were divided into 4 subgroups by k-means analysis: mild obesity-related diabetes (MOD), severe insulin-deficient diabetes (SIDD), severe insulin-resistant diabetes (SIRD), and mild age-related diabetes (MARD). After patients with insufficient data were excluded, further analysis was conducted on 246 T2DM patients. The TL was detected using telomere restriction fragment, and the related diabetic indexes were also measured by clinical standard procedures. Results: The MARD group had significantly shorter TLs than the MOD and SIDD groups. Then, we subdivided all T2DM patients into the MARD and NONMARD groups, which included the MOD, SIDD, and SIRD groups. The TLs of the MARD group, associated with age, were discovered to be significantly shorter than those of the NONMARD group (p = 0.0012), and this difference in TL disappeared after metformin (p = 0.880) and acarbose treatment (p = 0.058). The linear analysis showed that metformin can more obviously reduce telomere shortening in the MARD group (r = 0.030, 95% CI 0.010–0.051, p = 0.004), and acarbose can more apparently promote telomere attrition in the SIRD group (r = –0.069, 95% CI –0.100 to –0.039, p< 0.001) compared with other T2DM patients after adjusting for age and gender. Conclusions: The MARD group was found to have shorter TLs and benefit more from the antiaging effect of metformin than other T2DM. Shorter TLs were observed in the SIRD group after acarbose use.

1.
International Diabetes Federation
.
IDF Diabetes Atlas
.
Ninth
;
2019
.
2.
Ahlqvist
E
,
Storm
P
,
Käräjämäki
A
,
Martinell
M
,
Dorkhan
M
,
Carlsson
A
, et al.
Novel subgroups of adult-onset diabetes and their association with outcomes: a data-driven cluster analysis of six variables
.
Lancet Diabetes Endocrinol
.
2018
May
;
6
(
5
):
361
9
.
[PubMed]
2213-8587
3.
Zou
X
,
Zhou
X
,
Zhu
Z
,
Ji
L
.
Novel subgroups of patients with adult-onset diabetes in Chinese and US populations
.
Lancet Diabetes Endocrinol
.
2019
Jan
;
7
(
1
):
9
11
.
[PubMed]
2213-8587
4.
Shampay
J
,
Blackburn
EH
.
Tetrahymena micronuclear sequences that function as telomeres in yeast
.
Nucleic Acids Res
.
1989
Apr
;
17
(
8
):
3247
60
.
[PubMed]
0305-1048
5.
Sanchez
M
,
Hoang
S
,
Kannengiesser
C
,
Potier
L
,
Hadjadj
S
,
Marre
M
, et al.
Leukocyte Telomere Length, DNA Oxidation, and Risk of Lower-Extremity Amputation in Patients With Long-standing Type 1 Diabetes
.
Diabetes Care
.
2020
Apr
;
43
(
4
):
828
34
.
[PubMed]
0149-5992
6.
Mitteldorf
JJ
.
Telomere biology: cancer firewall or aging clock?
Biochemistry (Mosc)
.
2013
Sep
;
78
(
9
):
1054
60
.
[PubMed]
0006-2979
7.
Liu
M
,
Huo
YR
,
Wang
J
,
Wang
C
,
Liu
S
,
Liu
S
, et al.
Telomere Shortening in Alzheimer’s Disease Patients
.
Ann Clin Lab Sci
.
2016
May
;
46
(
3
):
260
5
.
[PubMed]
1550-8080
8.
Zhan
Y
,
Hägg
S
.
Telomere length and cardiovascular disease risk
.
Curr Opin Cardiol
.
2019
May
;
34
(
3
):
270
4
.
[PubMed]
0268-4705
9.
Hamel
FG
.
Telomeres and type 2 diabetes
.
Transl Res
.
2010
Apr
;
155
(
4
):
164
5
.
[PubMed]
1931-5244
10.
Chang
AM
,
Halter
JB
.
Aging and insulin secretion
.
Am J Physiol Endocrinol Metab
.
2003
Jan
;
284
(
1
):
E7
12
.
[PubMed]
0193-1849
11.
Geloneze
B
,
de Oliveira
MS
,
Vasques
AC
,
Novaes
FS
,
Pareja
JC
,
Tambascia
MA
.
Impaired incretin secretion and pancreatic dysfunction with older age and diabetes
.
Metabolism
.
2014
Jul
;
63
(
7
):
922
9
.
[PubMed]
0026-0495
12.
Rosa
EC
,
Dos Santos
RR
,
Fernandes
LF
,
Neves
FA
,
Coelho
MS
,
Amato
AA
.
Leukocyte telomere length correlates with glucose control in adults with recently diagnosed type 2 diabetes
.
Diabetes Res Clin Pract
.
2018
Jan
;
135
:
30
6
.
[PubMed]
0168-8227
13.
Bell
WR
,
Meeker
AK
,
Rizzo
A
,
Rajpara
S
,
Rosenthal
IM
,
Flores Bellver
M
, et al.
A unique telomere DNA expansion phenotype in human retinal rod photoreceptors associated with aging and disease
.
Brain Pathol
.
2019
Jan
;
29
(
1
):
45
52
.
[PubMed]
1015-6305
14.
Xiong
Y
,
Zhou
L
.
The Signaling of Cellular Senescence in Diabetic Nephropathy
.
Oxid Med Cell Longev
.
2019
Oct
;
2019
:
7495629
.
[PubMed]
1942-0900
15.
Ma
D
,
Zhu
W
,
Hu
S
,
Yu
X
,
Yang
Y
.
Association between oxidative stress and telomere length in Type 1 and Type 2 diabetic patients
.
J Endocrinol Invest
.
2013
Dec
;
36
(
11
):
1032
7
.
[PubMed]
1720-8386
16.
Campbell
JM
,
Bellman
SM
,
Stephenson
MD
,
Lisy
K
.
Metformin reduces all-cause mortality and diseases of ageing independent of its effect on diabetes control: A systematic review and meta-analysis
.
Ageing Res Rev
.
2017
Nov
;
40
:
31
44
.
[PubMed]
1568-1637
17.
Barzilai
N
,
Crandall
JP
,
Kritchevsky
SB
,
Espeland
MA
.
Metformin as a Tool to Target Aging
.
Cell Metab
.
2016
Jun
;
23
(
6
):
1060
5
.
[PubMed]
1550-4131
18.
Jiang
X
,
Ruan
XL
,
Xue
YX
,
Yang
S
,
Shi
M
,
Wang
LN
.
Metformin Reduces the Senescence of Renal Tubular Epithelial Cells in Diabetic Nephropathy via the MBNL1/miR-130a-3p/STAT3 Pathway
.
Oxid Med Cell Longev
.
2020
Feb
;
2020
:
8708236
.
[PubMed]
1942-0900
19.
Cameron
AR
,
Morrison
VL
,
Levin
D
,
Mohan
M
,
Forteath
C
,
Beall
C
, et al.
Anti-Inflammatory Effects of Metformin Irrespective of Diabetes Status
.
Circ Res
.
2016
Aug
;
119
(
5
):
652
65
.
[PubMed]
0009-7330
20.
Valencia
WM
,
Palacio
A
,
Tamariz
L
,
Florez
H
.
Metformin and ageing: improving ageing outcomes beyond glycaemic control
.
Diabetologia
.
2017
Sep
;
60
(
9
):
1630
8
.
[PubMed]
0012-186X
21.
de Kreutzenberg
SV
,
Ceolotto
G
,
Cattelan
A
,
Pagnin
E
,
Mazzucato
M
,
Garagnani
P
, et al.
Metformin improves putative longevity effectors in peripheral mononuclear cells from subjects with prediabetes. A randomized controlled trial
.
Nutr Metab Cardiovasc Dis
.
2015
Jul
;
25
(
7
):
686
93
.
[PubMed]
0939-4753
22.
Ma
D
,
Yu
Y
,
Yu
X
,
Zhang
M
,
Yang
Y
.
The changes of leukocyte telomere length and telomerase activity after sitagliptin intervention in newly diagnosed type 2 diabetes
.
Diabetes Metab Res Rev
.
2015
Mar
;
31
(
3
):
256
61
.
[PubMed]
1520-7552
23.
Liu
J
,
Ge
Y
,
Wu
S
,
Ma
D
,
Xu
W
,
Zhang
Y
, et al.
Association between antidiabetic agents use and leukocyte telomere shortening rates in patients with type 2 diabetes
.
Aging (Albany NY)
.
2019
Jan
;
11
(
2
):
741
55
.
[PubMed]
1945-4589
24.
American Diabetes Association
.
Standards of medical care in diabetes—2010
.
Diabetes Care
.
2010
Jan
;
33
Suppl 1
:
S11
61
.
[PubMed]
0149-5992
25.
Ouellette
MM
,
Liao
M
,
Herbert
BS
,
Johnson
M
,
Holt
SE
,
Liss
HS
, et al.
Subsenescent telomere lengths in fibroblasts immortalized by limiting amounts of telomerase
.
J Biol Chem
.
2000
Apr
;
275
(
14
):
10072
6
.
[PubMed]
0021-9258
26.
Jamieson
AR
,
Giger
ML
,
Drukker
K
,
Li
H
,
Yuan
Y
,
Bhooshan
N
.
Exploring nonlinear feature space dimension reduction and data representation in breast Cadx with Laplacian eigenmaps and t-SNE
.
Med Phys
.
2010
Jan
;
37
(
1
):
339
51
.
[PubMed]
0094-2405
27.
Zhu
Y
,
Liu
X
,
Ding
X
,
Wang
F
,
Geng
X
.
Telomere and its role in the aging pathways: telomere shortening, cell senescence and mitochondria dysfunction
.
Biogerontology
.
2019
Feb
;
20
(
1
):
1
16
.
[PubMed]
1389-5729
28.
Zee
RY
,
Castonguay
AJ
,
Barton
NS
,
Germer
S
,
Martin
M
.
Mean leukocyte telomere length shortening and type 2 diabetes mellitus: a case-control study
.
Transl Res
.
2010
Apr
;
155
(
4
):
166
9
.
[PubMed]
1931-5244
29.
Tamura
Y
,
Takubo
K
,
Aida
J
,
Araki
A
,
Ito
H
.
Telomere attrition and diabetes mellitus
.
Geriatr Gerontol Int
.
2016
Mar
;
16
Suppl 1
:
66
74
.
[PubMed]
1444-1586
30.
Savage
N
.
New tricks from old dogs join the fight against ageing. Nature 2017;552:S57-s59. Diman A, Boros J, Poulain F, Rodriguez J, Purnelle M, Episkopou H, Bertrand L, Francaux M, Deldicque L, Decottignies A: Nuclear respiratory factor 1 and endurance exercise promote human telomere transcription. Sci Adv 2016;2:e1600031. Kulkarni AS, Gubbi S, Barzilai N: Benefits of Metformin in Attenuating the Hallmarks of Aging. Cell Metab 2020. Aulinas A, Ramirez MJ, Barahona MJ, Valassi E, Resmini E, Mato E, Santos A, Crespo I, Bell O, Surralles J, Webb SM: Dyslipidemia and chronic inflammation markers are correlated with telomere length shortening in Cushing’s syndrome
.
PLoS One
.
2015
;
10
:
e0120185
.1932-6203
31.
Diman
A
,
Boros
J
,
Poulain
F
,
Rodriguez
J
,
Purnelle
M
,
Episkopou
H
, et al.
Nuclear respiratory factor 1 and endurance exercise promote human telomere transcription
.
Sci Adv
.
2016
Jul
;
2
(
7
):
e1600031
.
[PubMed]
2375-2548
32.
Kulkarni
AS
,
Gubbi
S
,
Barzilai
N
.
Benefits of Metformin in Attenuating the Hallmarks of Aging
.
Cell Metab
.
2020
Jul
;
32
(
1
):
15
30
.
[PubMed]
1550-4131
33.
Aulinas
A
,
Ramírez
MJ
,
Barahona
MJ
,
Valassi
E
,
Resmini
E
,
Mato
E
, et al.
Dyslipidemia and chronic inflammation markers are correlated with telomere length shortening in Cushing’s syndrome
.
PLoS One
.
2015
Mar
;
10
(
3
):
e0120185
.
[PubMed]
1932-6203
34.
Sharma
R
,
Gupta
A
,
Thungapathra
M
,
Bansal
R
.
Telomere mean length in patients with diabetic retinopathy
.
Sci Rep
.
2015
Dec
;
5
(
1
):
18368
.
[PubMed]
2045-2322
35.
Tentolouris
N
,
Nzietchueng
R
,
Cattan
V
,
Poitevin
G
,
Lacolley
P
,
Papazafiropoulou
A
, et al.
White blood cells telomere length is shorter in males with type 2 diabetes and microalbuminuria
.
Diabetes Care
.
2007
Nov
;
30
(
11
):
2909
15
.
[PubMed]
0149-5992
36.
Guadagnini
D
,
Rocha
GZ
,
Santos
A
,
Assalin
HB
,
Hirabara
SM
,
Curi
R
, et al.
Microbiota determines insulin sensitivity in TLR2-KO mice
.
Life Sci
.
2019
Oct
;
234
:
116793
.
[PubMed]
0024-3205
37.
Winer
DA
,
Luck
H
,
Tsai
S
,
Winer
S
.
The Intestinal Immune System in Obesity and Insulin Resistance
.
Cell Metab
.
2016
Mar
;
23
(
3
):
413
26
.
[PubMed]
1550-4131
38.
Henke
MT
,
Kenny
DJ
,
Cassilly
CD
,
Vlamakis
H
,
Xavier
RJ
,
Clardy
J
.
Ruminococcus gnavus, a member of the human gut microbiome associated with Crohn’s disease, produces an inflammatory polysaccharide
.
Proc Natl Acad Sci USA
.
2019
Jun
;
116
(
26
):
12672
7
.
[PubMed]
0027-8424
39.
Zhang
M
,
Feng
R
,
Yang
M
,
Qian
C
,
Wang
Z
,
Liu
W
, et al.
Effects of metformin, acarbose, and sitagliptin monotherapy on gut microbiota in Zucker diabetic fatty rats
.
BMJ Open Diabetes Res Care
.
2019
Sep
;
7
(
1
):
e000717
.
[PubMed]
2052-4897
40.
Valdes
AM
,
Andrew
T
,
Gardner
JP
,
Kimura
M
,
Oelsner
E
,
Cherkas
LF
, et al.
Obesity, cigarette smoking, and telomere length in women
.
Lancet
.
2005
Aug
;
366
(
9486
):
662
4
.
[PubMed]
0140-6736
41.
Vasan
RS
,
Demissie
S
,
Kimura
M
,
Cupples
LA
,
Rifai
N
,
White
C
, et al.
Association of leukocyte telomere length with circulating biomarkers of the renin-angiotensin-aldosterone system: the Framingham Heart Study
.
Circulation
.
2008
Mar
;
117
(
9
):
1138
44
.
[PubMed]
0009-7322
42.
Kimura
M
,
Stone
RC
,
Hunt
SC
,
Skurnick
J
,
Lu
X
,
Cao
X
, et al.
Measurement of telomere length by the Southern blot analysis of terminal restriction fragment lengths
.
Nat Protoc
.
2010
Sep
;
5
(
9
):
1596
607
.
[PubMed]
1754-2189
43.
Montpetit
AJ
,
Alhareeri
AA
,
Montpetit
M
,
Starkweather
AR
,
Elmore
LW
,
Filler
K
, et al.
Telomere length: a review of methods for measurement
.
Nurs Res
.
2014
Jul-Aug
;
63
(
4
):
289
99
.
[PubMed]
0029-6562
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