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Transcript of MSc in Diabetes A population approach Ross Lawrenson Postgraduate Medical School University of...
MSc in DiabetesA population approach
Ross LawrensonPostgraduate Medical School
University of Surrey
Impaired glucose tolerance and undiagnosed diabetes
UniS
Metabolic syndrome
• Impaired glucose tolerance
• Undiagnosed Type 2 diabetes
Theories on the aetiology of Type 2 diabetes
• Barker hypothesis
• Reaven Syndrome
• Thrifty genotype
Barker hypothesis
• The thrifty phenotype
Odds ratio of NIDDM and IGT related to birth weight
0
1
2
3
4
5
6
7
8
<=5.5 5.5-6.4 6.5-7.4 7.5-8.4 8.5-9.4 >9.5
Birth Weight in pounds
Odds Ratio
Barker hypothesis
• Malnutrition in the prenatal and early infant years. (Hales and Barker)
• Beta cells increase of 130 times between 12 th intra-uterine week and 5 th post natal month.
• Malnutrition.
• Obesity in later life.
Reaven syndrome
• First described by Himsworth in 1936
• Described in New Zealand by Ian Prior in 1966 in Maori (obesity, hypertension diabetes and gout)
• Syndrome X sometimes called Reaven syndrome after Gerry Reaven
Relationship between glucose uptake and fasting plasma glucose
0
100
200
300
400
500
600
700
0 50 100 150 200 250 300
NormalIGTNIDDM
Reaven G. Diabetes 1988
Reaven syndrome
• Reaven syndrome or Syndrome X– Resistance to insulin-stimulated glucose uptake
– Hyperinsulinaemia or glucose intolerance
– Hypertension
– Decreased HDL
– Increased VLDL
– Central obesity
Thrifty genotype
• Thrifty genotype– Ability to lay down fat
– Survive times of hardship
– Alternative metabolic pathway in high protein diet
Age adjusted prevalence of NIDDM and IGT in adults aged over 20 years
Maleeuropean
MaleAsian
FemaleEuropean
FemaleAsian
NIDDMknown
1.4% 7.2% 1.5% 6.8%
NIDDMnew
1.8% 5.2% 3.1% 4.3%
IGT 5.7% 9.8% 6.8% 11.2%
Total 8.9% 20.2% 11.4% 22.3%
Simmons D. The Coventry Diabetes Study. Quarterly Journal of Medicine. 1991; 81: 1021-1030
Prevalence of undiagnosed NIDDM with age in New Zealand adults aged over 20 years. The overall crude
rate was 56/3896 (1.4%).
20-2425-29
30-3435-39
40-4445-49
50-5455-59
60-6465-69
70-7475-79
80-8485-89
90+0
1
2
3
4
5
6
Age
Percent with undiagnosed NIDDM
Prevalence of undiagnosed NIDDM per 1000 people screened by BMI.
0-24 25-29 30-34 35-39 40+0
10
20
30
40
50
BMI
Prevalence per 1000
Mean BMI of men and women by ethnic origin.
Mean BMI 95% CI % with BMI >=30
Maori male 30.7 30.1 - 31.3 55%
Maori ethnic origin male 29.3 27.7 - 30.9 46%
European male 27.1 26.8 - 27.3 23%
Maori female 30.6 30.0 - 31.2 47%
Maori ethnic origin female 28.0 26.6 - 29.4 32%
European female 26.4 26.2 - 26.7 23%
Variables associated with the presence of undiagnosed diabetes in people 40 years.
Adjusted Odds Ratio 95% Confidence interval
Age 1.05 1.02 -1.07
BMI 1.09 1.03 - 1.15
Thirst 2.28 1.11 - 4.68
Ethnicity 2.26 1.08 - 4.72
Diastolic blood pressure 1.02 1.00 - 1.05
Gender 1.49 0.85 - 2.62 ns
Smoking .88 0.41 - 1.89 ns
Urinary frequency 1.04 0.57 - 1.89 ns
Significant factors associated with undiagnosed diabetes in Europeans over the age of 40 years.
Variable Adjusted OR95% Confidence interval
Age 1.07 1.04 - 1.10
BMI 1.13 1.06 - 1.21
Family history 2.34 1.16 - 4.71
Study using the General Practice Research Database - characteristics of subjects
Type 1Type 2
Mean age in 1992 33.4 63.6
Mean age at diagnosis (yrs) 18.0 56.7
Mean duration to 1992 (yrs) 16.2 7.1
Mean period of follow-up (yrs) 5.3 5.1
Total of 5528 type 1 and 25707 type 2 patients
Impaired glucose tolerance
• This group are asymptomatic and do not have diabetes
• Do not suffer the microvascular complications
• The diagnosis is important because:– High rate of macrovascular disease– A number will eventually become diabetic– Secondary prevention in this group may reduce
morbidity and mortality
Prevalence
Country/Race Male FemaleNauru 18.4 18.3
Papua New Guinea 3.5 1.2Italy 4.9 7.7
Australia 4.3 3.3
USA 10.2 11.1
Coventry Euro 5.7 6.8Coventry Asian 9.8 11.2
Progression to diabetes
Subjects studied Rate per yearBirmingham 4.5Sweden men 1.7
Bedford 1.5Japan 2.0
London men 2.9
Impaired glucose tolerance• After 10 years between 15 and 45% will have diabetes• After 10 years about 1/3 will be normal• If OGTT is repeated within 3 months approximately 50% will have a
normal GTT• Tukitonga showed that those with IGT in Niue who progressed to
diabetes were more likely to be sedentary whilst those who were active were more likely to return to normal
• Tuomilheto J, Lindstrom J, Eriksson JG, Valle TT, Hamalainen H, Ilanne-Parikka P et al. Prevention of Type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. New England Journal of Medicine 2001; 344(18) 1343-9
Summary• Type 2 diabetes is increasing
• Intervention strategies are needed to reduce incidence
• Identifying undiagnosed patients with type 2 diabetes may reduce onset of complications
• Identifying and treating IGT has proved worthwhile