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