7641 Epidemiology of Type 1 Diabetes

UniS 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) 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 Prevalence Prevalence of Type 1 diabetes per 1000 10 9 8 7 6 5 4 3 2 1 0 0 10 20 30 40 50 60 70 80 90 Male Female 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) 30 25 20 15 10 5 0 0-4 5 10 15 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. Molbak AG. Incidence of insulin-dependent diabetes mellitus in age groups over 30 years in Denmark. Diabet.Med. 1994; 11: 650-655. 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. 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 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 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 30 25 20 15 10 5 0 1978 1983 1988 1993 1998 0 to 4 5 to 9 10 to 14 Williams R. 2001 Geographical Variation 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 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 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) 35 30 25 20 15 10 5 0 Cases Ja n Fe b M ar A pr M ay Ju n A ug O ct N ov D ec Ju l Se p Ethnicity and genetics Ethnicity - incidence per 100,000 in different ethnic groups • US Virgin Islands – Hispanics – Whites – Blacks 7.2 28.9 5.9 • Hokkaido • Aust Euro 1.7 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. Kyvik,K. BMJ 1995;311:913-7 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. Deschamps I. Diabetologia 1992 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 • 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 35 30 25 20 15 10 5 0 -5 0 100 200 Yearly consumption of milk person/litre 300 Japan Incidence of Type 1 diabetes Finland Sweden UK Netherlands France NZ Countries Linear (Countries) Diabetes Care Nov 1991 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) 70 60 50 40 30 20 10 0 1 2 3 4 5 % developing diabetes I.F. Douek, P.J. Bingley, E.A.M. Gale. EASD Suppl 1999 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 Age at death 1-19 20-39 40-59 Male 2.3 3.1 3.3 Female 3.6 5.4 3.9 Laing et al BDA cohort study. Diabetic medicine 1999: 16;1-7 Survival (all causes of death): type 1 diabetes Probability of survival (%) 1 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0 30 40 50 60 Age 70 80 90 100 Non-diabetic males Non-diabetic females Males type 1 Females type 1 Mortality in Type 1 diabetes over time 1200 1000 800 600 400 200 0 1940-49 1950-59 1960-69 1970-79 1980-89 Male Female McNally P et al. Trends in mortality of childhood-onset insulindependent diabetes mellitus in Leicestershire: 1940-1991. Diabet.Med. 1995; 12: 961-966. 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