Exercise ameliorates serum MMP-9 and TIMP-2 levels in patients with type 2 diabetes.
OBJECTIVE
This study assessed the impact of regular exercise on inflammatory markers (high-sensitivity C-reactive protein [hsCRP], fibrinogen), and matrix metalloproteinases (MMPs) and their inhibitors (TIMPs), in patients with type 2 diabetes mellitus (T2DM).


METHODS
Fifty overweight patients with T2DM were randomly assigned to two groups: (A) an exercise group (EXG, n=25), with self-controlled exercise for at least 150 min/week and one additional supervised exercise session/week; and (B) a control group (COG, n=25), with no exercise instructions. All participants were taking oral antidiabetic drugs, and none had diabetic complications. Clinical parameters, exercise capacity (VO(2 peak)), ventilatory threshold (VT), insulin resistance indices (fasting insulin, HOMA-IR, HOMA%S), hsCRP, fibrinogen, MMP-2, MMP-9, TIMP-1 and TIMP-2 were assessed at baseline and after 16 weeks.


RESULTS
No significant changes were found in body mass index, waist/hip ratio, insulin-resistance indices, MMP-2 and TIMP-1 throughout the study in either group (P>0.05). Compared with controls, the EXG showed a significant decrease in systolic and mean blood pressure, total and LDL cholesterol, and HbA(1c) (P<0.05). Also, exercise significantly suppressed levels of fibrinogen (P=0.047), hsCRP (P=0.041) and MMP-9 (P=0.028), and the MMP-9-to-TIMP-1 ratio (P=0.038), whereas VO(2 peak) (P=0.011), VT (P=0.008) and plasma TIMP-2 levels (P=0.022) were considerably upregulated in the EXG vs. COG. Standard multiple-regression analyses revealed that MMP-9 changes were independently associated with fibrinogen and HbA(1c) changes, while fibrinogen changes independently predicted TIMP-2 alterations with exercise.


CONCLUSIONS
Mostly self-controlled exercise of moderate intensity ameliorated serum levels of pro- and anti-atherogenic markers in patients with T2DM, with no effects on body weight. These data offer further insight into the cardioprotective mechanisms of exercise in patients with T2DM.
1st Department of Internal Medicine, Hippokratio General Hospital of Thessaloniki, Thessaloniki, Greece. nikoskad@yahoo.com
N P E
NP
Kadoglou
I S
IS
Vrabas
N
N
Sailer
A
A
Kapelouzou
G
G
Fotiadis
G
G
Noussios
P E
PE
Karayannacos
N
N
Angelopoulou
D000368:Aged; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis; D016009:Chi-Square Distribution; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000201:enzymology / Q000628:therapy; D015444:Exercise / Q000502:physiology*; D005260:Female; D005340:Fibrinogen / Q000032:analysis; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood*; D008875:Middle Aged; D012044:Regression Analysis; D012307:Risk Factors; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000097:blood*
D015415:Biomarkers; D019716:Tissue Inhibitor of Metalloproteinase-2; D005340:Fibrinogen; D002097:C-Reactive Protein; D020780:Matrix Metalloproteinase 9