Lifestyle interventions to prevent diabetes and cardiovascular by hkksew3563rd

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									      Lifestyle interventions to prevent
diabetes and cardiovascular disease in
                                 PCOS.
                                           Dr Kathryn Hart RD
                                Division of Nutritional Sciences
                       Faculty of Health and Medical Sciences
                                           k.hart@surrey.ac.uk


      In collaboration with Dr Yvonne Jeanes & Suzanne Barr at
                                        Roehampton University
Presentation outline


• Multi-organ, multi-symptom, multi-stage
  condition
• Risk profile of PCOS sufferers
• Current lifestyle practices
  – Diet, exercise & alternative therapies
• Recommended lifestyle practices
  – Management of weight, central obesity &
    insulin resistance
PCOS – a multi-organ syndrome

                            pituitary




              liver
                                adrenals
                                ovaries
    adipose
     tissue
                       acne
                                              pituitary

               hirsuitism




               liver
                                               adrenals      excess
obesity                                                     androgens
                                                ovaries
     adipose                  infertility
      tissue                                                 menstrual
                                              Abnormal      disturbances
            Insulin                         gonadotrophin
          resistance                          dynamics
                       acne
                                              pituitary

               hirsuitism




               liver
                                               adrenals      excess
obesity                                                     androgens
                                                ovaries
     adipose                  infertility
      tissue                                                 menstrual
                                              Abnormal      disturbances
            Insulin                         gonadotrophin
          resistance                          dynamics
(Adapted from Moran
& Norman, 2004 &
Hopkinson et al., 1998)
                                      Insulin resistance
                                       Central obesity



                      Endocrine                             Metabolic
                     manifestations                        manifestations

                          ↑ insulin
                                                                glucose
                                                              intolerance
             liver        ovary        adrenal     hypertension         dyslipidaemia
     ↓ SHBG

                ↑ androgen activity
                                                              long term
                                                            consequences
                        clinical
                     presentation
 “Our aim here is to emphasize that women
  with PCOS should no longer be regarded
 as merely having reproductive or cosmetic
problems, but as having a metabolic disorder
  that potentially puts them at high risk for
  developing diabetes and heart disease.”


                             Sharma & Nestler, 2006
                          Endothelial
CVD risk profile          dysfunction

    Chronic low grade             Hypertension
    inflammation
                                        Impaired cardiopulmonary
    - ↑CRP                              functional capacity
    -↑WBC’s                             - ↑ Heart rate recovery

                 ↑PAI-1                                     excess
 obesity                                                   androgens


                                           Abnormal lipid profile
                                           - ↓ HDL
               Insulin                     - ↑ LDL (inc ↑ sml dense LDL)
             resistance                    - ↑ Triglycerides



                                          (see Giallauria et al 2008; Liepa et al
                                        2008; Westerveld et al 2008; Sharma &
                                                                   Nestler 2006)
                        Endothelial
CVD risk profile        dysfunction

    Chronic low grade           Hypertension
    inflammation
                                      Impaired cardiopulmonary
    - ↑CRP                            functional capacity
    -↑WBC’s                           - ↑ Heart rate recovery

               ↑PAI-1                                  excess
 obesity                                              androgens


                                        Abnormal lipid profile
                                        - ↓ HDL
             Insulin                    - ↑ LDL (inc ↑ sml dense LDL)
           resistance                   - ↑ Triglycerides
                                 Endothelial
CVD risk profile                 dysfunction

    Chronic low grade                    Hypertension
    inflammation
                                               Impaired cardiopulmonary
    - ↑CRP                                     functional capacity
    -↑WBC’s                 ↑ Thrombosis       - ↑ Heart rate recovery

                          ↑ Subclinical                          excess
                 ↑PAI-1
 obesity             atherosclerotic disease                    androgens
                          ↑ Early onset CVD
                                                 Abnormal lipid profile
                                                 - ↓ HDL
               Insulin                           - ↑ LDL (inc ↑ sml dense LDL)
             resistance                          - ↑ Triglycerides




                                                (Sharma & Nestler 2006, Talbott et al
                                                             2000, Wild et al 1985)
Diabetes risk profile




 obesity


                         menstrual
                        disturbances
             Insulin
           resistance
Diabetes risk profile




                        ↑ impaired glucose
                            tolerance

 obesity                ↑Early onset T2DM
                             ↑ T2DM
                        ↑Conversion IGT →                   menstrual
                             T2DM                          disturbances
             Insulin
           resistance



                                            (Liepa et al 2008; Legro et al 2005;
                                        Norman et al 2001; Ehrmann et al 1999;
                                                               Legro et al 1999)
Multi-organ/ symptom/ stage
…multi-approach?
• Focus on reducing long term risk as well as
  managing current symptoms
         ..this complex and multifaceted disease requires a
  comprehensive approach in order to achieve concrete beneficial
  effects for PCOS patients. Multidisciplinary programs, including
   dietary, and educational counselling, exercise training, stress
  management and psychosocial support, might represent the gold
                             standard..
                                                    Giallauria et al 2008




          • Majority of endocrinologists and gynaecologists believe
          that the first line of treatment for all presentations of PCOS
          should be diet & exercise (Cussons et al 2005)
Multi-organ/ symptom/ stage
…multi-approach?
• Focus on reducing long term risk as well as
  managing current symptoms


      Diet     Exercise    Psychological   +/-   Pharmacological Rx
                           support


       Lifestyle therapy
Aims of lifestyle intervention
                    Overweight/ obese?


         Yes                                No

      ↓ weight
                                      Central obesity?
    Initial 5-10%
     Long term               Yes                             No
   maintenance of
      10-20%              ↓ waist
                                                         IGT/ Insulin
                        measurement
                                                         resistance?


                                              Yes
                                            ↑ insulin
                                           sensitivity
What management strategies are
wPCOS using?

• Postal survey – strategies used & benefits
  perceived
  – Exercise
     • 48% (100/208) reported increasing exercise to
       manage their condition with a further 2% (5/208)
       attempting to reduce stress
     • Of these women 80% (86/107) believed these
       lifestyle changes had improved their symptoms,
       15% (16/107) reported no change and only 2
       women (2%) felt their condition had worsened
– Exercise
                                                                      Percentage of
    • Current activity levels                vigorous                  time spent in
                                              activity
                                                                    physical activity,
                                          m oderate
                                           activity
                                                                         by intensity
                                                                          (n=194, postal
                                                                                survey)




                                                         light activity




 Time (mins) spent in moderate or vigorous activity
 (n=194, postal survey)
               12000


               10000
mean steps/d




                8000


                6000


                4000


                2000


                   0
                       whole sample (n=38)   <25.0 kg/m2 (n=24)   >=25.0 kg/m2 (n=14)


                                               BMI group
                       Mean steps per day (n=38, observational study)
– Exercise
  • Current activity levels
     – Self reported exercisers not significantly more
       active than others, although trend towards
       increased time spent in vigorous activity (12.04
       [28.1] mins ‘v’ 5.74 [11.0], Z= -1.8, p=0.07)

     – Step counts negatively correlated with waist
       measurement (r = -0.36, p=0.03) and positively
       correlated with HDL (r = 0.54, p=0.001)
     – Trend towards a correlation with %body fat
       (r = -0.31, p=0.07)
– Alternative therapies
  • 41% (85/208) reported using some form of natural
    remedy or supplement with 54% perceiving an
    improvement
                         25

                         20
      Frequency




                         15

                         10

                          5

                          0




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      Natural remedies and supplements taken by women with PCOS
       – Dietary strategies:
            • 55% were following a specific diet to manage their
            PCOS

                                                     Low GI 49%
Food avoidance (e.g.
                                                     Other 26%
   wheat) modified
protein & fruit intakes                              Low fat 10%

                                                     Reduced sugar 9%

                                                     Healthy Eating 6%


                    Dietary strategies employed by women with PCOS
What should they be using?
• Weight management
  – NICE (2006)
     • Use multi-component interventions (behavioural change,
       activity/ inactivity, energy intake, diet quality)
     • Assess readiness to change & explore barriers to change
     • Provide tailored advice

  – National Obesity Forum (2006)
     • First line: achieve 500kcal deficit through changes in diet &
       physical activity
     • Second line: consider drug treatments, behavioural therapy,
       alternative therapies, specialist obesity clinic, surgery

           • Focus on maintenance not just loss
           – successful maintainers = low fat diet, regular self
           monitoring, high physical activity (Wing & Hill 2001)
 What should they be using?
                          May → greater wt              Sig ↓ BMI ‘v’
                          loss than exercise               control
                             (10% ‘v’ 5%)               (Vigorito et al
           Diet alone                                       2007)
                             (Palomba et al
                                 2008)
Range of dietary                                          Exercise
interventions →                                            alone
5-15% ↓ wt                    Weight management
(Moran et al 2008)                in wPCOS

                                       Combined
       ↓6.3-10.2kg in 6mths
                                        approach
       (Clark et al 1995 & 1998)    (exercise, diet &   NB. Generally
                                       behaviour)       uncontrolled
                                                        studies
 What should they be using?

• Reducing central obesity
  – Exercise
    • Higher levels of physical activity associated with
      ↓central fat (cross sectional & intervention) (Kim et al.,
      2008; Samaras & Campbell, 1997)

    • ↓ waist (0.2-2.9cm) seen in overweight women in
      long term physical activity interventions (time >
      intensity) (Lau et al 2007)
    • Interval training and progressive resistance training
      have positive effects on trunk fat in T2DM which
      may be indep of body mass (Kay & Fiatarone Singh, 2006)
 What should they be using?

• Reducing central obesity
  – Exercise (continued)
    • Aerobic & resistance exercise may affect fat stores
      via different methods (Van Etten et al 1995) BUT resistance
      exercise may have practical benefits over aerobic
    • Moderate & high intensive exercise shown to be
      effective for reducing abdominal fat but
      ? effectiveness of lower intensities (Kay & Fiatarone Singh,
      2006)
What should they be using?

• Reducing central obesity
  – Diet
    • MUFA rich diets (‘v’ CHO rich) associated with ↓
      central fat redistribution (Paniagua et al., 2007)
    • Potential role of high dairy calcium in promoting fat
      loss independent of weight loss (e.g. Zemel et al 2005)
    • Higher wholegrain intakes associated with lower
      central adiposity in cross sectional studies (Harland &
      Garton 2008)

    • Wholegrain enriched hypocaloric diet → sig
      ↓abdominal fat ‘v’ refined grain diet in obese adults
      with Metabolic Syndrome (Katcher et al 2008)
What should they be using?
                        ↓ central obesity in
                             wPCOS

              Diet +
                                                   Exercise
             exercise
                                                    alone
   20wk hypocaloric
                        12 week programme       3-6mth structured
  diet +/- exercise →
                            of nutrition or          exercise
  sig ↓waist (11%).
                         nutrition + exercise      programmes
  + Exercise → 45%      → sig ↓waist (~5%).      (aerobic) → sig
  greater ↓ body fat                             greater ↓waist
                               ↓
                          12%↓ skinfold
    ‘v’ diet alone                              circumference ‘v’
                            thickness in
 (Thomson et al 2008)   combined approach          control/ diet
                        ‘v’ 3% in diet alone    (Vigorito et al 2007,
                          No sig ↓weight        Palomba et al 2008)

                          (Bruner et al 2006)
What should they be using?

• Increasing insulin sensitivity
  – Exercise
     • acute exercise and training→ ↑ insulin sensitivity of
       skeletal muscle & ↑ glucose tolerance and insulin
       sensitivity
     • short term effects of exercise seen independent of
       changes in adiposity
     • Resistance training → improved muscle quality
       (strength & fibre composition) → ↑glucose uptake
       (Brooks et al., 2007)

     • regular physical activity may prevent or delay
     development of T2DM (indep. of starting BMI), e.g. DaQuing
     study
• Increasing insulin sensitivity
  – Exercise
     • protective effect of physical activity strongest for
      individuals at highest risk of developing T2DM
      (Barwell et al 2008, Ivy 1997)
What should they be using?

• Increasing insulin sensitivity
  – Diet
     1. FAT
     • High MUFA (‘v’ high SFA) significantly improves
       insulin sensitivity in healthy, obese & T2DM (Vessby et al
      2001, Summers et al 2003)

     • ↑ total fat → ↓ insulin sensitivity BUT mediated by
       weight
     • Increase in total fat from 20% → 40% energy has NO
       impact on insulin sensitivity when corrected for wt.
      (Ricardi & Rivellese, 2000)
• Increasing insulin sensitivity
  – Diet
     2. Carbohydrate (Volek & Feinman, 2005)
     • Quality – lower GI/ GL
     • Quantity - reduced CHO (even without wt loss or in
       comparison to low fat) can have positive impact on
       fasting & post challenge insulin (Douglas et al 2006)
        • Replace CHO with…nothing or MUFA or protein
        • ~40% CHO (from 55%), very low carbohydrate diets
          not necessary
     • Wholegrains → ↓postprandial glucose due to slower
       digestion & absorption (Kaline et al 2007)
     • ↑ dietary fibre intakes associated with ↑insulin
       sensitivity (Liese et al 2005)
• Increasing insulin sensitivity
  – Diet
     3. Supplements
     • Chromium
        • may ↑insulin sensitivity in T2DM (Martin et al., 2006)
        • ? deficiency associated with insulin resistance (Diabetes
           Education, 2004)

     • Vitamin D replenishment improves glycaemia &
       insulin secretion in T2DM (Palomer et al 2008)
     • Inconclusive evidence for the effect of cinnamon on
       insulin resistance – may have a moderate effect in
       lowering plasma glucose in poorly controlled T2DM
      (Pham et al 2007)
 What should they be using?
                            V low CHO →
        Diet                   ↓insulin
                                                                 Exercise
                            (Hays et al 2003)
  Higher protein →
    ↓postprandial                                                  6mth structured
   glucose (‘v’ low                                             exercise → 41% ↓IR
       protein)                                                independent of weight
                                                                 loss (‘v’ 9% for diet
  (Moran et al 2003)         ↑ Insulin sensitivity in                   alone)
                                    wPCOS                       (Palomba et al 2008)

NB. All overwt/ obese
Some uncontrolled +/-
small samples
                                     Supplementation

               Cinnamon extract       Chromium may ↑        Vit D supplementation
                 may ↓ insulin        glucose disposal      → ↑insulin secretion &
                  resistance                rate            improved lipid profile
               (Wang et al 2007)       (Lydic et al 2006)      (Kotsa et al 2008)
What should they be using?

• Summary
  – Exercise recommendations
     • Exercise of benefit across PCOS population BUT ?
       Type/ duration & intensity
     • Aim for adherence over intensity
     • General population guidelines remain appropriate
       (and sufficiently challenging!) targets for many, e.g.
       30mins, 5x week
     • Promote global and concrete benefits, e.g. ↓stress,
       ↑self esteem, ↓waist
     • Emphasise benefits for increase/ maintenance of
       LBM, esp. for those aiming to lose weight
What should they be using?

• Summary
  – Diet recommendations
     • Low saturated fat (<10%) (replace with MUFA) and
       low-moderate total fat (<30-37% energy)
     • High fibre/ wholegrain carbohydrate choices
     • 20% E from protein, increased (with ↓CHO) if
       required for satiety/ wt control
     • Energy restriction for weight loss (200-500kcal/d)
     • Adequate intake of n3 fats, e.g. 1-2 portions/ wk
       oily fish (or fish oil/ flaxseed oil)
     • Adequate intake of Vitamin D and calcium
What should they be using?

• Summary
  – General recommendations
     • Avoid ‘scale obsession’ - improvements in
       abdominal obesity and insulin sensitivity may occur
       without significant ↓wt
     • ‘standard practice’ ‘v’ ‘specialised practice’ - if
       overweight or obese → effective weight loss
       strategies as 1st line treatment
     • Psychological & social support – importance in
       non-PCOS weight loss/ behaviour change
       recognised and suggestion that psychological
       ‘need’ may be even greater in PCOS
Conclusion

• Therapeutic management of PCOS must
  recognise it multi-organ, multi-feature, multi-
  stage nature.
• Substantial evidence from the insulin resistance/
  diabetes literature can be translated into
  appropriate interventions for the PCOS
  population
• Further robust research is needed within the
  lean PCOS population specifically to fill in the
  gaps where more specialised approaches may
  be warranted.
Acknowledgements

  Dr Yvonne Jeanes & Suzanne Barr (Roehampton)


  Internal funding from University of Surrey & Roehampton University


  All students and technical staff who have assisted with the studies


  All women who have participated in the research
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    Nutrition. 21:323-41.
•   Zemel MB, Richards J, Mathis S et al (2005) Dairy augmentation of total and central
    fat loss in obese subjects. Int J Obes. 29(4):391-7.
DaQuing Study
Exercise: ↑ daily leisure physical activity




                                              50% reduction in progression
                                              to T2DM with exercise +/- diet



                                                   Pan et al 1997, cited in Ruderman et
                                                   al., 1998
Why target this group?




                                                  Lack of National guidelines/ consistent
  Clinical need                   Personal need




                                                         management strategies
                      Cost
                  effectiveness

								
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