Summary
The objective of the present study was to assess the prevalence of familial aggregation of Type 1 (insulin-dependent) diabetes mellitus among Danish families with a diabetic child aged 20 years or less and to compare epidemiological data for familial and sporadic cases. We attempted to identify all patients with Type 1 diabetes aged 0–19 years in Denmark treated at paediatric departments or at departments of internal medicine. This comprises more than 98% of all patients with Type 1 diabetes in this age group. Patients were identified through the local diabetic out-patient registry and asked to complete a questionnaire regarding data on diabetes onset and family history. Of 1574 probands 1419 agreed to participate (90.2%). Additional cases of Type 1 diabetes were found in 171 families (12.8%). Of these 115 were parent-offspring affected families, and in 56 families at least two siblings had Type 1 diabetes and healthy parents. Significant correlation in age at onset of Type 1 diabetes in concordant siblings was observed (r=0.5, p=0.0004). Significantly more probands had an affected father with Type 1 diabetes than a mother affected (p<0.0001). Heterogeneity in epidemiological characteristics was observed between familial and sporadic cases, i.e. familial index cases were younger at onset of the disease, their parents were younger at birth of the index case, and there was no difference in gender of familial cases in contrast to sporadic cases where significantly more males were found. Over a 4-year period (1986–1989) an increasing trend in incidence was observed. However, an increase in incidence compared to previous Danish data from the 1970s and 1980 s could not be demonstrated.
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References
Diabetes Epidemiology Research International Group (1988) Geographic patterns of childhood insulin-dependent diabetes mellitus. Diabetes 37: 1113–1119
The WHO Multinational Project for Childhood Diabetes Group (1991) Familial insulin-dependent diabetes mellitus (IDDM) epidemiology: standardization of data for the DIAMOND project. Bull WHO 69: 767–777
Field LL (1988) Insulin-dependent diabetes mellitus: a model for the study of multifactorial disorders. Am J Hum Genet 43: 793–798
Thomson G, Robinson WP, Kuhner MK et al. (1988) Genetic heterogeneity, modes of inheritance, and risk estimates for a joint study of Caucasians with insulin-dependent diabetes mellitus. Am J Hum Genet 43: 799–816
Dorman JS, LaPorte RE, Stone RA, Trucco M (1990) Worldwide differences in the incidence of type I diabetes are associated with amino acid variation at position 57 of the HLA-DQ β chain. Proc Natl Acad Sci USA 87: 7370–7374
Degnbøl B, Green A (1978) Diabetes mellitus among first- and second degree relatives of early onset diabetics. Ann Hum Genet 42: 25–47
Jaworski MA, Colle E, Guttmann RD et al. (1980) Insulin dependent diabetes: a comparison of families with single and multiple affected siblings. Diabetologia 19: 97–100
Gamble DR (1980) An epidemiological study of childhood diabetes affecting two or more siblings. Diabetologia 19: 341–344
Wagener DK, Sacks JM, LaPorte RE, MacGregor JM (1982) The Pittsburgh study of insulin-dependent diabetes mellitus. Risk for diabetes among relatives of IDDM. Diabetes 31: 136–144
Chern MM, Anderson VE, Barbosa J (1982) Empirical risk for insulin-dependent diabetes (IDD) in sibs. Further definition of genetic heterogeneity. Diabetes 31: 1115–1118
Cheta D, Dumitrescu C, Georgescu M et al. (1990) A study of the types of diabetes mellitus in first degree relatives of diabetic patients. Diabete Metab 16: 11–15
Warram JH, Krolewski AS, Gottlieb MS, Kahn CR (1984) Differences in risk of insulin-dependent diabetes in offspring of diabetic mothers and diabetic fathers. N Engl J Med 311: 149–152
Tillil H, Köbberling J (1987) Age-corrected empirical genetic risk estimates for first degree relatives of IDDM patients. Diabetes 36: 93–99
Dahlquist G, Blom L, Tuvemo T, Nyström L, Sandström A, Wall S (1989) The Swedish childhood diabetes study — Results from a nine year case register and a one year case-referent study indicating that type 1 (insulin-dependent) diabetes mellitus is associated with both type 2 (non-insulin-dependent) diabetes mellitus and autoimmune disorders. Diabetologia 32: 2–6
Tuomilehto J, Lounamaa R, Tuomilehto-Wolf E et al. (1992) Epidemiology of childhood diabetes mellitus in Finland — background of a nationwide study of type 1 (insulin-dependent) diabetes mellitus. Diabetologia 35: 70–76
Tuomilehto J, Podar T, Reunanen A et al. (1991) Comparison of incidence of IDDM in childhood between Estonia and Finland, 1980–1988. Diabetes Care 14: 982–988
Christau B, Kromann H, Andersen O et al (1977) Incidence, seasonal and geographical patterns of juvenile-onset insulin-dependent diabetes mellitus in Denmark. Diabetologia 13: 281–284
Mortensen HB, Hartling SG, Petersen KE, The Danish Study Group of Diabetes in Childhood (1988) A nation-wide cross-sectional study of glycosylated haemoglobin in Danish children with type 1 diabetes. Diabetic Med 5: 871–876
Mortensen HB, Marinelli K, Nørgaard K et al. (1990) A nationwide cross-sectional study of urinary albumin excretion rate, arterial blood pressure and blood glucose control in Danish children with type 1 diabetes. Diabetic Med 7: 887–897
Statistisk Arbog (Statistical Yearbook) 1991. Danmarks Statistik, Copenhagen
Sukkersyge. Organisation af undersøgelse og behandling (1981) Sundhedsstyrelsen (National Board of Health), Copenhagen
Dahlquist G, Blom L, Holmgren G et al. (1985) The epidemiology of diabetes in Swedish children 0–14 years — a six-year prospective study. Diabetologia 28: 802–808
Joner G, Søvik O (1989) Increasing incidence of diabetes mellitus in Norwegian children 0–14 years of age, 1973–1982. Diabetologia 32: 79–83
Blohmé G, Nyström L, Arnqvist HJ et al. (1992) Male predominance of type 1 (insulin-dependent) diabetes mellitus in young adults: results from a 5-year prospective nationwide study of the 15–34-year age group in Sweden. Diabetologia 35: 56–62
O'Leary LA, Dorman JS, LaPorte RE et al. (1991) Familial and sporadic insulin-dependent diabetes: evidence for heterogeneous etiologies. Diabetes Res Clin Pract 14: 183–190
Gamble DR, Taylor KW (1969) Seasonal incidence of diabetes mellitus. BMJ 3: 631–633
Green A, Andersen PK (1983) Epidemiological studies of diabetes mellitus in Denmark: 3. Clinical characteristics and incidence of diabetes among males aged 0 to 19 years. Diabetologia 25: 226–230
Bingley PJ, Gale EAM (1989) Incidence of insulin dependent diabetes in England: a study in the Oxford region, 1985–6. BMJ 298: 558–560
Flood TM, Brink SJ, Gleason RE (1982) Increased incidence of type I diabetes in children of older mothers. Diabetes Care 5: 571–573
Wagener DK, LaPorte RE, Orchard TJ, Cavender D, Kuller LH, Drash AL (1983) The Pittsburgh diabetes mellitus study 3: An increased prevalence with older maternal age. Diabetologia 25: 82–85
Warram JH, Krolewski AS, Kahn CR (1988) Determinants of IDDM and perinatal mortality in children of diabetic mothers. Diabetes 37: 1328–1334
Warram JH, Martin BC, Krolewski AS (1991) Risk of IDDM in children of diabetic mothers decreases with increasing maternal age at pregnancy. Diabetes 40: 1679–1684
McCarthy BJ, Dorman JS, Aston CE (1991) Investigating genomic imprinting and susceptibility to insulin-dependent diabetes mellitus: an epidemiological approach. Genet Epidemiol 8: 177–186
Takemore T, Rajewski K (1984) Mechanism of neonatally induced idiotype suppression and its relevance for the acquisition of self-tolerance. Immunol Rev 79: 103–117
Vadheim CM, Rotter JI, MacLaren NK, Riley WJ, Anderson E (1986) Preferential transmission of diabetic alleles within the HLA gene complex. N Engl J Med 315: 1314–1318
Swain JL, Stewart TA, Leder P (1987) Parental legacy determines methylation and expression of an autosomal transgene: a molecular mechanism for parental imprinting. Cell 50: 719–727
Hall JG (1990) Genomic imprinting: review and relevance to human disease. Am J Hum Genet 46: 857–873
Julier C, Hyer RN, Davies J et al. (1991) Insulin-IGF2 region on chromosome 11 p encodes a gene implicated in HLA-DR4-dependent diabetes susceptibility. Nature 354: 155–159
Mølbak AG, Nørgaard K, Christau B, Kjær M, Nerup J (1987) Secular trend in the incidence of insulin-dependent diabetes mellitus in Denmark. Acta Endocrinol 115 [Suppl 289]: 48 (Abstract)
Green A, Gale EAM, Patterson CC, the EURODIAB ACE Study Group (1992) Incidence of childhood-onset insulin-dependent diabetes mellitus: the EURODIAB ACE study. Lancet 339: 905–909
Patterson CC, Smith PG, Webb J, Heasman MA, Mann JI (1988) Geographical variation in the incidence of diabetes mellitus in Scottish children during the period 1977–1983. Diabetic Med 5: 160–165
Burden AC, Hearnshaw JR, Swift PGF (1989) Childhood diabetes mellitus: an increasing incidence. Diabetic Med 6: 334–336
Soltész G, Madácsy L, Békefi D, Dankó I, the Hungarian Childhood Diabetes Epidemiology Group (1990) Rising incidence of type 1 diabetes in Hungarian children (1978–1987). Diabetic Med 7: 111–114
Tuomilehto J, Rewers M, Reunanen A et al. (1991) Increasing trend in type 1 (insulin-dependent) diabetes mellitus in childhood in Finland. Analysis of age, calender time and birth cohort effects during 1965 to 1984. Diabetologia 34: 282–287
Green A, Andersen PK, Svendsen AJ, Mortensen K (1992) Increasing incidence of early onset type 1 (insulin-dependent) diabetes mellitus: a study of Danish male birth cohorts. Diabetologia 35: 178–182
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The Danish Study Group of Diabetes in Childhood is an association of paediatricians with a special interest in diabetes research. For participating departments in the present study see Acknowledgements
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Pociot, F., Nørgaard, K., Hobolth, N. et al. A nationwide population-based study of the familial aggregation of Type 1 (insulin-dependent) diabetes mellitus in Denmark. Diabetologia 36, 870–875 (1993). https://doi.org/10.1007/BF00400364
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DOI: https://doi.org/10.1007/BF00400364