MSc in Diabetes A population approach

1
MSc in DiabetesA population approach
UniS
Epidemiology of Type 1 Diabetes
Ross Lawrenson Postgraduate Medical
School University of Surrey
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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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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
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Prevalence
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Prevalence of Type 1 diabetes per 1000
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Incidence
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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)
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Type 1 in older patients

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

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Type 1 in older patients

• 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.
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Gender

• 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.
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Gender

• 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
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Type 1 Diabetes

• Increasing incidence

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Increasing incidence

• 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.
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Type 1 diabetes is becoming commoner in children
Williams R. 2001
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Geographical Variation
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Adjusted incidence per 100,000 person year of
Type 1 diabetes under 15 yr (1980)

• Finland
• Sweden
• Scotland
• England
• Netherlands
• France

• 29.5
• 22.4
• 19.9
• 15.6
• 9.7
• 4.4

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

• Canada PEI
• Minnesota
• Colorado
• California
• Cuba

• 25.5
• 20.8
• 15.1
• 9.4
• 2.6

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Geographical Variation

• 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.

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Geographical variation

• 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 .

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Seasonal variation
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Number of cases per month of Type 1 diabetes
(n226)
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(No Transcript)
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Ethnicity and genetics
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Ethnicity - incidence per 100,000 in different
ethnic groups

• US Virgin Islands
• Hispanics 7.2
• Whites 28.9
• Blacks 5.9
• Hokkaido 1.7
• Aust Euro 13.2

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Genetics

• 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 1995311913-7
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Genetic susceptibility

• 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

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Risk of Type 1 diabetes in siblings.

• 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
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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
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Nicotinamide

• 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)

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Cows milk
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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
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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

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Maternal age
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Maternal age

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

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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
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Viruses

• Coxsackievirus and cytomegalovirus have both been
  implicated.
• Multiple infections in early infancy seem to be
  protective

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Mortality and Morbidity
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Mortality

• Mortality in UK patients with Type 1 diabetes

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SMR by age and sex for people with Type 1 diabetes
Laing et al BDA cohort study. Diabetic medicine
1999 161-7
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Survival (all causes of death) type 1 diabetes
Probability of survival ()
Age
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Mortality in Type 1 diabetes over time
McNally P et al. Trends in mortality of
childhood-onset insulin-dependent diabetes
mellitus in Leicestershire 1940-1991.
Diabet.Med. 1995 12 961-966.
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Summary of aetiological findings

• Type 1 diabetes is increasing
• Probably caused by a combination of genetic and
  environmental influences
• Role of cows milk?
• Nicotinamide?
• Seasonal variation
• Diet?
• Viruses?

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Conclusion

• 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