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Uni S. MSc in Diabetes A population approach. Epidemiology of Type 1 Diabetes. Ross Lawrenson Postgraduate Medical School University of Surrey. Type 1 Diabetes. An auto immune disorder characterised by islet cell destruction Used to equate to insulin dependent diabetes mellitus (IDDM).

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Msc in diabetes a population approach l.jpg

UniS

MSc in DiabetesA population approach

Epidemiology of Type 1 Diabetes

Ross Lawrenson

Postgraduate Medical School

University of Surrey


Type 1 diabetes l.jpg
Type 1 Diabetes

  • An auto immune disorder characterised by islet cell destruction

  • Used to equate to insulin dependent diabetes mellitus (IDDM)


Diagnosis l.jpg
Diagnosis?

  • Insulin dependent diabetes associated with auto antibodies e.g Islet Cell Antibodies (ICA) Insulin Autoantibodies (IAA) and Glutamic Acid Decarboxylase Antibodies (GADA) - 90% of white children with newly diagnosed diabetes have auto antibodies

  • Some apparent type 1 diabetics have no demonstrable auto antibodies - 10%

  • Epidemiological definition is IDDM developing in people before age of 35 years

Atkinson MA, Eisenbarth GS. Lancet 2001; 358: 221-9





Slide7 l.jpg
Incidence of Type 1 Diabetes - new cases for every 100,000 per year by age groups 0-4, 5-9,10-14,15-19 (1992)


Type 1 in older patients l.jpg
Type 1 in older patients per year by age groups 0-4, 5-9,10-14,15-19 (1992)

  • Both these ladies developed diabetes at the age of 48 years.


Type 1 in older patients9 l.jpg
Type 1 in older patients per year by age groups 0-4, 5-9,10-14,15-19 (1992)

  • A study Danish adults over the age of 30 has found an incidence rate of type 1 diabetes of 8.2 cases/100,000/year.

  • This rate is lower than that found in Danish children (21.5 cases/100,000/year)

  • Assuming that all type 1 diabetes is incident in children might lead to an underestimation the incidence of type 1 diabetes in the population as a whole.

  • Molbak AG. Incidence of insulin-dependent diabetes mellitus in age groups over 30 years in Denmark. Diabet.Med. 1994; 11: 650-655.


Gender l.jpg
Gender per year by age groups 0-4, 5-9,10-14,15-19 (1992)

  • With the exception of one study from America, no difference in incidence of type 1 diabetes in children has been observed between males and females.

  • The American study suggested a male excess

  • Allen C et al. Incidence and differences in urban-rural seasonal variation of type 1 (insulin-dependent) diabetes in Wisconsin. Diabetologia 1986; 29: 629-633.


Gender11 l.jpg
Gender per year by age groups 0-4, 5-9,10-14,15-19 (1992)

  • No sex-specific significant difference is apparent in the prevalence of type 1 diabetes in children,

  • In adults appears more prevalent in men, with a prevalence of 0.42% of men aged 25-29, but 0.19% of women.

  • This male excess disappears in older age groups - above 65 years of age the prevalence is 0.11% in men and 0.08% in women.

Waugh NR et al.The Dundee prevalence study of insulin-treated diabetes;

intervals between diagnosis and start of insulin therapy. Diabet.Med. 1989; 6: 346-350


Type 1 diabetes12 l.jpg
Type 1 Diabetes per year by age groups 0-4, 5-9,10-14,15-19 (1992)

  • Increasing incidence


Increasing incidence l.jpg
Increasing incidence per year by age groups 0-4, 5-9,10-14,15-19 (1992)

  • UK

    • 1951-60: 3.8 per 100,000

    • 1961-70: 5.3 per 100,000

    • 1971-80: 10.6 per 100,000

    • 1985-95: 18.6 per 100,000

Gardner et al. BMJ 1998 showed a 4% annual increase in

incidence since 1985 and in the under fives this was an 11% increase.


Type 1 diabetes is becoming commoner in children l.jpg
Type 1 diabetes is becoming commoner in children per year by age groups 0-4, 5-9,10-14,15-19 (1992)

Williams R. 2001


Geographical variation l.jpg
Geographical Variation per year by age groups 0-4, 5-9,10-14,15-19 (1992)


Adjusted incidence per 100 000 person year of type 1 diabetes under 15 yr 1980 l.jpg

Finland per year by age groups 0-4, 5-9,10-14,15-19 (1992)

Sweden

Scotland

England

Netherlands

France

29.5

22.4

19.9

15.6

9.7

4.4

Adjusted incidence per 100,000 person year of Type 1 diabetes under 15 yr (1980)


Adjusted incidence per 100 000 person year of type 1 diabetes under 15 yr 198017 l.jpg

Canada PEI per year by age groups 0-4, 5-9,10-14,15-19 (1992)

Minnesota

Colorado

California

Cuba

25.5

20.8

15.1

9.4

2.6

Adjusted incidence per 100,000 person year of Type 1 diabetes under 15 yr (1980)


Geographical variation18 l.jpg
Geographical Variation per year by age groups 0-4, 5-9,10-14,15-19 (1992)

  • A variation in incidence of type 1 diabetes in the British Isles has been observed.

  • Rates in Scotland (20 cases/100,000/year), Wessex (17.1 cases/100,000/year) and East Anglia (17.7 cases/100,000/year), whilst significantly lower rates were found in the Thames region (8-12 cases/100,000/year), Northern Ireland (10.9 cases/100,000/year) and Eire (6.8 cases/100,000/year).

  • No geographical pattern is apparent within the variation, and the hypothesis of a North-South difference is not supported.


Geographical variation19 l.jpg
Geographical variation per year by age groups 0-4, 5-9,10-14,15-19 (1992)

  • Statistically significant clustering of incidence has been noted in Yorkshire, even at the ward level, as well as in Northern Ireland and Scotland.

  • The clustering of incident cases of type 1 diabetes has been linked with deprivation and household crowding and suggest environmental, rather than genetic, components.

  • A role for ecological factors, such as nitrates in drinking water, cannot be excluded.

  • Geographical variation is not unique to Britain: in Finland regional differences have been observed, with an inverse correlation between population density and incidence of type 1 diabetes .


Seasonal variation l.jpg
Seasonal variation per year by age groups 0-4, 5-9,10-14,15-19 (1992)


Number of cases per month of type 1 diabetes n 226 l.jpg
Number of cases per month of Type 1 diabetes (n=226) per year by age groups 0-4, 5-9,10-14,15-19 (1992)


Ethnicity and genetics l.jpg
Ethnicity and genetics per year by age groups 0-4, 5-9,10-14,15-19 (1992)


Ethnicity incidence per 100 000 in different ethnic groups l.jpg
Ethnicity - incidence per 100,000 in different ethnic groups per year by age groups 0-4, 5-9,10-14,15-19 (1992)

  • US Virgin Islands

    • Hispanics 7.2

    • Whites 28.9

    • Blacks 5.9

  • Hokkaido 1.7

  • Aust Euro 13.2


Genetics l.jpg
Genetics per year by age groups 0-4, 5-9,10-14,15-19 (1992)

  • If an identical twin has Type 1 diabetes then in 50% of cases the other twin will also develop Type 1 diabetes.

  • If the twins are not identical then less than 10% chance.

Kyvik,K. BMJ 1995;311:913-7


Genetic susceptibility l.jpg
Genetic susceptibility per year by age groups 0-4, 5-9,10-14,15-19 (1992)

  • HLA-DR3 and HLA-DR4 are more likely to develop Type 1 diabetes

  • HLA-DR2 seems protective

  • Genetics cannot be specified on classical lines of dominant, recessive or intermediate genes


Risk of type 1 diabetes in siblings l.jpg
Risk of Type 1 diabetes in siblings. per year by age groups 0-4, 5-9,10-14,15-19 (1992)

  • 4% developed Type 1 diabetes by age 22 years.

  • 12% risk in those with HLA DR3 or DR4

  • 56% with raised Islet Cell Antibodies went on to diabetes.

Deschamps I. Diabetologia 1992


Use of nicotinamide in children with high levels of circulating ica l.jpg
Use of nicotinamide in children with high levels of circulating ICA.

  • 8 children who were 1 st degree relatives of Type 1 diabetics with ICA levels above 80 units were followed for 5 years. All became diabetic after a mean 17 months.

  • 14 other children who were 1 st degree relatives and had raised ICA were given 150 - 300 mg Nicotinamide and followed for 5 years.

  • 1 became diabetic after 25 months

  • Has led to a major RCT (report in 2003)

Elliott R. Diabetologia 1991


Nicotinamide l.jpg
Nicotinamide circulating ICA.

  • DENIS (Deutsche Nicotinamide Intervention Study) showed no difference in randomised trial involving 55 children for 3 years. (Lampeter EF. Klinghammer A. Scherbaum WA. Heinze E. Haastert B. Giani G. Kolb H. The Deutsche Nicotinamide Intervention Study: an attempt to prevent type 1 diabetes. DENIS Group. Diabetes. 1998; 47(6):980-4)

  • Much larger multi national randomised trial (ENDIT) will report in 2003 (Gale et al)


Cows milk l.jpg
Cows milk circulating ICA.


Incidence of type 1 diabetes in relation to mean yearly consumption of cows milk l.jpg
Incidence of Type 1 diabetes in relation to mean yearly consumption of cows milk

Finland

Sweden

UK

NZ

Netherlands

France

Japan

Diabetes Care Nov 1991


Cows milk32 l.jpg
Cows milk consumption of cows milk

  • Exclude cows milk from rats diet and the incidence of diabetes falls.

  • Children with diabetes have been breast fed for a shorter period than controls.

  • Western Samoan children did not get Type 1 diabetes until they moved to New Zealand


Maternal age l.jpg
Maternal age consumption of cows milk


Maternal age34 l.jpg
Maternal age consumption of cows milk

  • Recent study have suggested Type 1 diabetes in children maybe associated with maternal age


Slide35 l.jpg
Cumulative risk of developing diabetes in siblings of children with Type 1 diabetes in quintiles (median age range 21 -34 years)

I.F. Douek, P.J. Bingley, E.A.M. Gale. EASD Suppl 1999


Viruses l.jpg
Viruses children with Type 1 diabetes in quintiles (median age range 21 -34 years)

  • Coxsackievirus and cytomegalovirus have both been implicated.

  • Multiple infections in early infancy seem to be protective


Mortality and morbidity l.jpg

Mortality and Morbidity children with Type 1 diabetes in quintiles (median age range 21 -34 years)


Mortality l.jpg
Mortality children with Type 1 diabetes in quintiles (median age range 21 -34 years)

  • Mortality in UK patients with Type 1 diabetes


Smr by age and sex for people with type 1 diabetes l.jpg
SMR by age and sex for people with Type 1 diabetes children with Type 1 diabetes in quintiles (median age range 21 -34 years)

Laing et al BDA cohort study. Diabetic medicine 1999: 16;1-7


Slide40 l.jpg

Survival (all causes of death): type 1 diabetes children with Type 1 diabetes in quintiles (median age range 21 -34 years)

Probability of survival (%)

Age


Mortality in type 1 diabetes over time l.jpg
Mortality in Type 1 diabetes over time children with Type 1 diabetes in quintiles (median age range 21 -34 years)

  • McNally P et al. Trends in mortality of childhood-onset insulin-dependent diabetes mellitus in Leicestershire: 1940-1991. Diabet.Med. 1995; 12: 961-966.


Summary of aetiological findings l.jpg
Summary of aetiological findings children with Type 1 diabetes in quintiles (median age range 21 -34 years)

  • Type 1 diabetes is increasing

  • Probably caused by a combination of genetic and environmental influences

  • Role of cows milk?

  • Nicotinamide?

  • Seasonal variation

    • Diet?

    • Viruses?


Conclusion l.jpg
Conclusion children with Type 1 diabetes in quintiles (median age range 21 -34 years)

  • Incomplete information on aetiological factors

  • A number of possibilities for prevention have been raised but have yet to lead to a worthwhile population approach

  • Still great potential for preventing increase in developed communities


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