Msc in Diabetes a population approach Type 1 Diabetes

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