MSc in Diabetes a population approach Type 1 Diabetes



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MSc in Diabetes A population approach


Type 1 Diabetes

  • An auto immune disorder characterised by islet cell destruction

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



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



Prevalence



Prevalence of Type 1 diabetes per 1000



Incidence



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

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



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.



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



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.



Type 1 Diabetes

  • Increasing incidence



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


Type 1 diabetes is becoming commoner in children



Geographical Variation



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

  • Finland

  • Sweden

  • Scotland

  • England

  • Netherlands

  • France



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

  • Canada PEI

  • Minnesota

  • Colorado

  • California

  • Cuba



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.



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 .



Seasonal variation



Number of cases per month of Type 1 diabetes (n=226)





Ethnicity and genetics



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



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.



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



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.



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)



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)



Cows milk



Incidence of Type 1 diabetes in relation to mean yearly consumption of cows milk



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



Maternal age

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



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



Viruses

  • Coxsackievirus and cytomegalovirus have both been implicated.

  • Multiple infections in early infancy seem to be protective



Mortality and Morbidity



Mortality

  • Mortality in UK patients with Type 1 diabetes



SMR by age and sex for people with Type 1 diabetes





Mortality in Type 1 diabetes over time



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?


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




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