Impact of Aerobic Exercise Training on Insulin Sensitivity

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					                                                                                        IMPACT OF ENDURANCE EXERCISE ON INSULIN SENSITIVITY, PHYSICAL FITNESS AND
                                                                                            MUSCLE OXIDATIVE CAPACITY IN OFFSPRING OF TYPE 2 DIABETIC PATIENTS
                                                                                                                                             Torben Østergård 1, Kevin R Short 2, Bengt Saltin 3, KS Nair 2, Ole Schmitz 1
                                                                                                                                      1Medical
                                                                                                                                Dpt. M (Endocrinology and Diabetes), Aarhus University Hospital, Denmark;
                                                                                      2    Division of Endocrinology, Mayo Clinic and Foundation, Rochester, MN, USA; 3Copenhagen Muscle Research Center, Rigshospitalet, Denmark


             First-degree relatives of type 2 diabetic patients (FDR) are
                                                                                                                                                                                                                                                                                                                                                                                                                         r=0.06, P=0.76                                                                                                 r=0.57, P=0.01
             often employed when studying potentially early steps in the
                                                                                                                                                                                                                                                                                                                                                                                                               6                                                                                                       6




  1          development of type 2 diabetes. Insulin resistance and
                                                                                                                                   3                                                                                                                                                    Control
                                                                                                                                                                                                                                                                                                                                       5                                                                       4                                                                                                       4




                                                                                                                                                                                                                                                                                                                                                                                           ∆ISGU (mg/kg/min)




                                                                                                                                                                                                                                                                                                                                                                                                                                                                             ∆ISGU (mg/kg/min)
             impaired physical capacity (VO2max) are frequently                                                                                                                                                                    FDR                                                                                     p                                                                                   2                                                                                                       2

                                                                                                                                                                                                                                                                                        subjects
             demonstrated in healthy and normal glucose tolerant FDR.                                                                                                                                                                                                                                                                                                                                          0                                                                                                       0


                                                                                                                                                     N                                                                             29                                                   19
Background


                                                                                                                                                                                                                                                                                                                                                                                                               -2                                                                                               -2

             Both insulin sensitivity and VO2max are associated with
                                                                                                                                                     Gender (m/f)                                                                  19/10                                                14/5
             skeletal muscle oxidative capacity. Interestingly, evidence of
                                                                                                                                                                                                                                                                                                                                                                                                               -4                                                                                               -4
                                                                                                                                                                                                                                                                                                                                                                                                                    -5     0           5        10         15      20   25                                                         -5      0     5         10        15          20      25

                                                                                                                                                                                                                                                                                                                                                                                                                                       ∆VO2max (ml/kg/min)                                                                                       ∆VO2max (ml/kg/min)

             reduced muscle oxidative capacity and impaired                                                                                          Age (years)                                                                   33.3 ± 5.5                                           30.7 ± 5.5                         0.11
             mitochondrial function have recently been demonstrated in                                                                               BMI (kg/m 2)                                                                  26.3 ± 1.6                                           25.8 ± 3.0                         0.54
                                                                                                                                                                                                                                                                                                                                                                                                                                      Changes in insulin sensitivity and in VO2max were only
                                                                                                                                                                                                                                                                                                                                                                                                                                                    related in control subjects
             both patients with type 2 diabetes (1) as well as in healthy




                                                                                                                                  Subjects
             first-degree relatives of patients with type 2 diabetes (2).                                                                            Waist-hip ratio                                                               0.90 ± 0.05                                          0.89 ± 0.07                        0.31
                                                                                                                                                                                                                                                                                                                                                                                      70
                                                                                                                                                                                                                                                                                                                                                                                                                                    P=0.12
                                                                                                                                                                                                                                                                                                                                                                                                                                              P=0.32                                                                               50                              P=0.10




                                                                                                                                                                                                                                                                                                                                     Results
             Thus, as mitochondrial dysfunction might link insulin                                                                                   F-p-glucose (mM)                                                              5.3 ± 0.5                                            5.1 ± 0.3                          0.07                                                                                                                                                                                                                          P=0.07




                                                                                                                                                                                                                                                                                                                                                   COX enzyme activity (arb. units)
                                                                                                                                                                                                                                                                                                                                                                                      60




                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 CS enzyme activity (arb. units)
             resistance and decreased VO2max we sought to explore
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   40
                                                                                                                                                                                                                                                                                                                                                                                      50                                                             *
                                                                                                                                                                                                                                                                                                                                                                                                                                *                                                                                                                                         *
             whether first-degree relatives differ in the ability to improve                                                                         F-s-insulin (pM)                                                              54 ± 29                                              55 ± 30                            0.98                                                       40                                                                                                                                           30                *

             skeletal muscle oxidative capacity, insulin sensitivity and




                                                                                                                                                                                                                                                                                                                                                                                                                                    Post-ex



                                                                                                                                                                                                                                                                                                                                                                                                                                                         Post-ex
                                                                                                                                                                                                                                                                                                                                                                                      30




                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         Post-ex



                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               Post-ex
                                                                                                                                                                                                                                                                                                                                                                                                                         Pre-ex



                                                                                                                                                                                                                                                                                                                                                                                                                                               Pre-ex
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   20




                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               Pre-ex



                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    Pre-ex
                                                                                                                                                     F-C-peptide                                                                   646 ± 207                                            531 ± 150                          0.04*
             physical capacity compared with a group of age, gender and
                                                                                                                                                                                                                                                                                                                                                                                      20
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   10
                                                                                                                                                                                                                                                                                                                                                                                      10

             BMI matched control group.                                                                                                              VO2 max (ml/kg/min)                                                           38.0 ± 6.5                                           40.8 ± 6.1                         0.14                                                       0
                                                                                                                                                                                                                                                                                                                                                                                                                               Offspring             Controls
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    0
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  Offspring               Controls

             1. Kelley DE, He J, Menshikova EV, Ritov VB. Dysfunction of mitochondria in human skeletal muscle in type 2                             Insulin sensitivity, M
             diabetes. Diabetes 2002; 51(10):2944-2950.                                                                                                                                                                            5.5 ± 1.9                                            7.2 ± 2.6                          0.01*                                                                         At baseline COX and CS enzyme activities in skeletal muscle tended to be
             2. Petersen KF, Dufour S, Befroy D, Garcia R, Shulman GI. Impaired mitochondrial activity in the insulin-resistant                      (mg/kg/min)
             offspring of patients with type 2 diabetes. N Engl J Med 2004; 350(7):664-671.
                                                                                                                                                                                                                                                                                                                                                                                                       reduced in first-degree relatives. Exercise increased enzyme activities in both
                                                                                                                                                                                                                                                                                                                                                                                                       groups (* P < 0.001). The magnitude of these changes did not differ between
                                                                                                                                                                                                                                                                                                                                                                                                                             first-degree relatives and controls.




             Inclusion criterias:                                                                                                                                                                                                                                                                                                                  In conclusion:
             •Sedentary (VO2max ≤ 50 ml/kg/min)                                                                                                                                                     r=0.009, P=0.96
                                                                                                                                                                                                                                                                                                                                                   In conclusion, this study shows that first-degree
                                                                                                                                                                                 16                                                                                     16
                                                                                                                                                                                                                                                                                        r=0.67, P=0.002




                                                                                                                                                                                                                                                                                                                                     Conclusions
2                                                                                                                                 4
                                                                                                                                                                                 14                                                                                     14

             •Age 20-50 years                                                                                                                                                                                                                                                                                                                      relatives of type 2 diabetic patients are able to




                                                                                                                                                         ISGU (mg/kgLBM/min)




                                                                                                                                                                                                                                                  ISGU (mg/kgLBM/min)
                                                                                                                                                                                 12                                                                                     12


             •BMI ≤ 30 kg/m2                                                                                                                                                     10                                                                                     10
                                                                                                                                                                                                                                                                                                                                                   respond adequately to endurance training in terms
             •Normal glucose tolerance                                                                                                                                               8                                                                                         8



             •Offspring: at least two relatives diagnosed with type 2                                                                                                                6                                                                                         6                                                                   of changes in VO2max and insulin sensitivity.
             diabetes (at least one parent)
                                                                                                                                                                                     4                                                                                         4
                                                                                                                                                                                                                                                                                                                                                   However, contrasting that of the control group we
                                                                                                                                                                                                                                                                                                                                                   found a lack of a significant correlation between the
                                                                                                                                                                                     2                                                                                         2

             •Control subjects: no relatives diagnosed with type 2                                                                                                                            35      40     45      50     55

                                                                                                                                                                                                              VO2max (ml/kgLBM/min)
                                                                                                                                                                                                                                   60   65   70                                    35     40      45       50   55    60

                                                                                                                                                                                                                                                                                                   VO2max (ml/kgLBM/min)
                                                                                                                                                                                                                                                                                                                           65   70




             diabetes                                                                                                                                                                               At baseline insulin sensitivity and VO2max did only correlate in controls
                                                                                                                                                                                                                                                                                                                                                   increased VO2max and insulin sensitivity. In
             Exercise-protocol:                                                                                                                                                                                                                                                                                                                    accordance with previous studies we found
             10 weeks of cycle-ergometer training, 3 times per week, 45
                                                                                                                                                                                                                                                                                                                                                   indications of reduced oxidative capacity (citrate
                                                                                                                                  Results
                                                                                                                                                                                               55                                                                                  10
Design




             minutes each session at 70% of VO2max.                                                                                                                                            50
                                                                                                                                                                                                                                                                                   9                                                               synthase and cytochrome c oxidase activities) in
                                                                                                                                                                                                                                                                                                                                                   first-degree relatives of type 2 diabetic patients.
                                                                                                                                                                         VO2max (ml/kg/min)




                                                                                                                                                                                                                                                            ISGU (mg/kg/min)
             Before and after the training period:
                                                                                                                                                                                                                                                                                   8


                                                                                                                                                                                                                                                                                                                                                   Whether these observations are interrelated cannot
                                                                                                                                                                                               45


             •Hyperinsulinemic (1 mU/kg/min), euglycemic (5 mmol/l)
                                                                                                                                                                                                                                                                                   7



             glucose clamp for 150 minutes (M-value).
                                                                                                                                                                                               40
                                                                                                                                                                                                                                                                                   6                                                               be determined by this study. Nonetheless, in the
                                                                                                                                                                                               35
                                                                                                                                                                                                                                                                                   5                                                               light of previous reports documenting reduced
             •Incremental maximal exercise test (bicycle ergometer test)                                                                                                                                   Pre-ex vs. post-ex: P<0.001                                                         Pre-ex vs. post-ex: P<0.05
                                                                                                                                                                                               30                                                                                  4                                                               oxidative capacity in type 2 diabetic subjects and
                                                                                                                                                                                                                                                                                                                                                   their offspring we consider it to be a very tempting
                                                                                                                                                                                                            Week 0        Week 5   Week 10                                                        Pre-ex        Post-ex
             •Skeletal muscle citrate synthase (CS) and cytochrome c
             oxidase (COX) activites                                                                                                                                                                       VO2max and insulin sensitivity were improved equally in both
                                                                                                                                                                                                                                                                                                                                                   hypothesis.
                                                                                                                                                                                                               first-degree relatives (●) and control subjects (o)

				
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Description: Aerobic exercise refers to increased heart rate, increase the workload of the lungs and heart movement, need to speed up the operation of the heart and lungs to the body parts to improve the amount of oxygen, it can accelerate the blood circulation of oxygen in the process, including jogging, running, swimming, cycling, rowing and jumping and so is aerobic exercise.