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Preventing and reversing type 2 diabetes _PowerPoint_ - Robert

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Preventing and reversing type 2 diabetes _PowerPoint_ - Robert Powered By Docstoc
					Preventing and reversing
    type 2 diabetes
               Robert Schmidli
               Endocrinologist
        MB ChB, MRCP, FRACP, PhD
Senior Staff Specialist, The Canberra Hospital
    Senior Lecturer, ANU Medical School


       www.schmidli.com.au
            Lecture outline
   Background
   Diabetes prevention
   Diabetes reversal
Background
                  History
   1425 – “diabete” recorded
    in medical text
   1675 – “mellitus”
    – sweet taste of urine
   1889 – removal of
    pancreas in dogs
   Pre-1921 – diabetes uniformly fatal
   1921 – treatment of diabetic boy with
    insulin derived from human pancreas
   Long-term complications
           Other milestones
   1936 – type 1 distinct from type 2
    diabetes
   1942 – sulphonylureas for type 2
    diabetes
   1950s – biguanides
    (phenformin/metformin)
   1960 – measurement of insulin
   1993 – relationship between control
    and complications (1998 type 2)
       Definition of diabetes
         “Elevation of blood glucose
        due to an absolute or relative
               lack of insulin”

Type 1 diabetes:
      Lack of insulin due to destruction of insulin-producing
      beta cells
Type 2 diabetes:
      Complex multisystem condition
     Definition of diabetes and “pre-
                 diabetes”
                      Diabetes
    • Fasting               > 7.0mmol/l
    • 2 hr after glucose    > 11.1mmol


                 Pre-diabetes
   Impaired glucose tolerance
    • 2 hr after glucose    7.8 – 11mmol/l
   Impaired fasting glucose
    • Fasting               5.6 – 6.9mmol/l
 What is insulin?

       Insulin




                 Cell

Receptor
    Defects in type 2 diabetes




Reduced insulin                                           Increased blood
                      Pancreas
    production                    Blood glucose
                                                          glucose levels


                                                       Adipose
                                                       tissue (fat)
                          Liver
       Excessive
          glucose
                                         Muscle
  production from
                                                  Resistance to action of
              liver
                                                  insulin

                                                    Adapted from Saltiel 1996, Jones 1999
                Genetics

   “Single gene diabetes” (MODY) rare
   Strong inheritance
   Polygenic – involves multiple genes
   Risk in unaffected identical twin 90%
   Huge difference in ethnic groups
    despite same environment
              Lifestyle factors
   Inadequate exercise
    • Sedentary occupations
    • Automation
    • Long working hours
   Diet
    • Excess food available
    • Processed food
   Sleep disorders
    • Reduced sleep
    • Sleep apnoea (3x more common in diabetes)
Progression of type 2 diabetes
Obesity            Pre-     Diabetes         Diabetes
Insulin resistance diabetes (diet/tablets)   (insulin-requiring)




                             Insulin resistance




                             Insulin production

                          Time
                  Diabetic complications

Retinopathy
Diabetes is the
most common
cause of visual loss                                                                                           Cardiovascular
in Australian adults                                                                                           disease
< 60 y.o.                                                                                                      The most common
                                                                                                               cause of death in
                                                                                                               people with diabetes



Nephropathy                                                                                                    Diabetic
Diabetes is a leading                                                                                          neuropathy
cause of end-stage renal                                                                                       Foot ulcers, gangrene,
disease                                                                                                        amputations




       DOHW Report 1999 www.health.gov.au/internet/wcms/publishing.nsf/Content/health-pq-diabetes-pubs-diabetes99.htm Accessed November 29 2007.
              Diabetes in Australia
   AusDiab study
    • 42 randomly selected sites
    • 11,247 individuals tested
   Results
    •   7.5% of population ≥25y diabetic, 8.0% ♂, 7.0 ♀
    •   ≥ 75 years 23.6% diabetic
    •   50% undiagnosed
    •   30% high blood pressure or on treatment
    •   1/6 no physical activity, 50% 150 min/week
    •   1,000,000 Australians with diabetes
    •   60% overweight or obese, 2.5x that in 1980
    •   Number with diabetes has trebled since 1981
              Drug treatment
   ↑ Insulin secretion
    • Sulphonylureas
    • GLP-1 analogues
   Insulin sensitisers
    • Metformin
    • “Glitazones”
   ↓ glucose absorption
    • Acarbose
   Insulin
Diabetes prevention
Diabetes/Prediabetes screening
   Age ≥50y
   Age ≥45 plus
    • Obesity (BMI 30 kg/m2)
    • First-degree relative with type 2 diabetes
    • Hypertension
   Aboriginal and Torres Strait Islanders ≥35
   High-risk non–English-speaking ≥ 35y
   Impaired glucose tolerance/fasting glucose
   Clinical cardiovascular disease
   Women with previous gestational diabetes
   Obese women with polycystic ovary syndrome
    Diabetes Prevention Program
   USA study
   Over 3000 obese individuals with IGT
   Target:   7% weight loss
              150 min/week exercise
   Compared to:
    • Metformin
    • Placebo (information on diet/exercise)
Diabetes Prevention Program
                     Reductions
                      Metformin
                       31%
                      Lifestyle
                       58%
          Problems with DPP
            Cost effectiveness
   Cost over 30 years:
    • Lifestyle intervention   $62,600
    • Metformin                $35,400
    • Delay until onset        $24,500

          Usefulness in “real life”
   Long-term adherence out of research
    project poor
     Drug prevention of diabetes
   Numerous drugs shown to reduce
    progression from pre-diabetes
    • Metformin
    • Sulphonylureas
    • Glitazones
    • Acarbose
   Benefit no greater than lifestyle
   May simply mask rise in blood glucose
   Risk probably reverts if drug stopped
   Huge numbers, costly
   Health benefits unknown
     Population health measures
   Advertising restrictions
   Education programs
   Media publicity
   Cost incentives/disincentives
   Limiting food types (eg schools)
   Exercise programs in
    schools/workplaces

      Few of these used to date
Diabetes reversal
           Diabetes reversal
   No published evidence with standard
    lifestyle measures
   Prevention more important
   May occur with major lifestyle
    change
   Increased interest in surgical weight
    loss
   “Remission” not “Cure”
    • Normal blood glucose off medications
          Criteria for surgery
   Failed dietary/lifestyle management
   BMI ≥ 40
   Other conditions (diabetes, sleep
    apnoea, joints etc) and BMI ≥ 35
   Acceptable surgical risk
   Well motivated
         Restrictive procedures
Laparoscopic adjustable gastric   Vertical banded gastroplasty
banding “lap-band”                “stomach stapling”
Roux-en-Y gastric bypass
            Other procedures
                           “Cosmetic” procedures
   Apronectomy            Fat usually reaccumulates
   Abdominoplasty         High complication rate
   Liposuction            No reversal of diabetes
                           Not recommended



   Jejuno-ileal bypass         “Desperate” cases
   Biliopancreatic diversion   Seldom done in Aus
   Above + duodenal switch     Complications
     Analysis of bariatric surgery
   134 studies, 22,094 patients

                                 Mean ↓wt
                   No patients      (kg)
Total population         7588         39.7
Gastric banding           482         28.6
Gastric bypass           2742            43
Gastroplasty              936         39.8
B/P diversion,
duod switch              1282         46.4
       Improvement in diabetes

                   Complete                   FBG
                   resolution   HbA1C (%)   (mmol/l)
                      (%)         Drop        Drop

Total population        76.8          2.4         3.9

Gastric banding         47.8          1.2         3.1

Gastric bypass          83.8            3         3.4

Gastroplasty            68.2                      4.8
B/P diversion,
duod switch             97.9                      5.8
              Conclusions
   Diabetes may be preventable and
    reversible
   Usually controlled rather than cured
   Lifestyle measures essential but
    unlikely to reverse diabetes
   Surgery useful in selected individuals
   Few attempts at population approach

				
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