Familiality of Diabetes Mellitus

 

 Buy Article Permissions and Reprints

Abstract

The aims of this study were to estimate relative risk for type 1 and type 2 diabetes in relatives of diabetic patients, and to test for excess relatedness among diabetic patients. Additionally, the difference in parental transmission of diabetes was investigated. This study used a unique Utah genealogical resource, linked to electronic medical records of the largest health provider in Utah. We identified 19,640 patients with a diagnosis of type 1 or type 2 diabetes. Relative Risks (RRs) for type 1 and type 2 diabetes were assessed for first-, second- and third-degree relatives of diabetic patients. The observed average relatedness of diabetic patients was compared to the expected relatedness using the Genealogical Index of Familiality (GIF). We observed significantly elevated RRs for type 1 diabetes in first-degree (RR=8.68; P<0.0001), second-degree (RR=1.93; P<0.0001) and third-degree relatives (RR=1.74; P<0.0001) of type 1 diabetic patients. RRs for type 2 diabetes were significantly increased in first-degree (RR=2.24; P<0.0001), second-degree (RR=1.36; P<0.0001) and third-degree relatives (RR=1.14; P<0.0001) of type 2 diabetic patients. Significantly increased RRs for type 1 diabetes were observed in the relatives of type 2 diabetic patients, and vice versa. The GIF analysis showed significant excess relatedness for type 1 diabetes cases, and independently for type 2 diabetes cases. Offspring of diabetic fathers were at significantly higher risk for type 1 diabetes than offspring of diabetic mothers (RR=9.73; P<0.0001 compared to RR=4.99; P<0.0001). No significant difference in parental transmission was observed for type 2 diabetes. Our results strongly support the existence of a genetic contribution to both type 1 and type 2 diabetes, and additionally suggest a relationship between both types of diabetes. Furthermore, our results suggest a significant difference in parental transmission of type 1 diabetes.

References

• 1 Allen-Brady K, Camp NJ, Ward JH, Cannon-Albright LA. Lobular breast cancer: excess familiality observed in the Utah Population Database.  Int J Cancer. 2005;  117 655-661
  CrossrefPubMedGoogle Scholar
• 2 Bean LL, Mineau GP, Anderton DL. Fertility Change on the American Frontier. Berkeley, CA, University of California Press 1990
• 3 Bleich D, Polak M, Eisenbarth GS, Jackson RA. Decreased risk of type 1 diabetes in offspring of mothers who acquire diabetes during adrenarchy.  Diabetes. 1993;  42 1433-1439
  CrossrefPubMedGoogle Scholar
• 4 Bureau of Health Promotion . , Hispanic and Latino Health in Utah: A Diabetes Report. Utah Department of Health, Salt Lake City (UT), 2003. Available from http://health.utah.gov/diabetes/pdf/fctsandfig/diabeteshispanic.pdf , Accessed 21 April 2006
• 5 Camp NJ, Farnham JM, Cannon Albright LA. Genomic search for prostate cancer predisposition loci in Utah pedigrees.  Prostate. 2005;  65 365-374
  CrossrefPubMedGoogle Scholar
• 6 Cannon-Albright LA, Camp NJ, Farnham JM, MacDonald J, Abtin K, Rowe KG. Genealogical assessment of heritable predisposition to aneurysms.  J Neurosurg. 2003;  99 637-643
  PubMedGoogle Scholar
• 7 Cannon-Albright LA, Thomas A, Goldgar DE, Gholami K, Rowe K, Jacobsen M, MacWorther WP, Skolnick MH. Familiality of cancer in utah.  Cancer Res. 1994;  54 2378-2385
  PubMedGoogle Scholar
• 8 Carel JC, Boitard C, Bougneres PF. Decreased insulin response to glucose in islet cell antibody-negative siblings of type 1 diabetic children.  J Clin Invest. 1993;  92 509-513
  PubMedGoogle Scholar
• 9 Chern MM, Anderson VE, Barbosa J. Empirical risk for insulin-dependent diabetes (IDD) in sibs. Further definition of genetic heterogeneity.  Diabetes. 1982;  31 1115-1118
  CrossrefPubMedGoogle Scholar
• 10 Dahlquist G, Blom L, Tuvemo T, Nystrom L, Sandstrom A, Wall S. 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. 1989;  32 2-6
  PubMedGoogle Scholar
• 11 Dean L, MacEntyre J. The Genetic Landscape of Diabetes.  , National Library of Medicine (US) (online book), 2004. Available from http://www.ncbi.nlm.nih.gov/books/bv.fcgi?idref=diabetes , Accessed 10 January, 2006
  PubMedGoogle Scholar
• 12 Elbein SC, Chiu KC, Permutt MA. Type 2 diabetes mellitus. In: King A, Rotter JI, Motulsky AG (eds). The Genetics Basis of Common Disease. New York: Oxford University Press 2002: 457-480
  Google Scholar
• 13 Fagerudd JA, Pettersson-Fernholm KJ, Grönhagen-Riska C, Groop PH. The impact of a family history of Type II (non-insulin-dependent) diabetes mellitus on the risk of diabetic nephropathy in patients with Type I (insulin-dependent) diabetes mellitus.  Diabetologia. 1999;  42 519-526
  CrossrefPubMedGoogle Scholar
• 14 Goldgar DE, Easton DF, Cannon Albright LA, Skolnick MH. Systematic population-based assessment of cancer risk in first-degree relatives of cancer probands.  Journal of the National Cancer Institute. 1994;  86 1600-1608
  CrossrefPubMedGoogle Scholar
• 15 Gottlieb MS. Diabetes in offspring and siblings of juvenile- and maturity-onset-type diabetics.  J Chronic Dis. 1980;  33 331-339
  CrossrefPubMedGoogle Scholar
• 16 Groop L, Forsblom C, Lehtovirta M, Tuomi T, Karanko S, Nissen M, Ehrnstrom BO, Forsen B, Isomaa B, Snickars B, Taskinen MR. Metabolic consequences of a family history of niddm (the botnia study): evidence for sex-specific parental effects.  Diabetes. 1996;  5 1585-1593
  PubMedGoogle Scholar
• 17 Horne BD, Camp NJ, Muhlestein JB, Cannon Albright LA. Evidence for a heritable component in death resulting from aortic and mitral valve diseases.  American Heart Association. 2004;  110 3143-3148
  PubMedGoogle Scholar
• 18 Horne BD, Camp NJ, Muhlestein JB, Cannon-Albright LA. Identification of excess clustering of coronary heart diseases among extended pedigrees in a genealogical population database.  Am Heart J. 2006;  152 305-311
  CrossrefPubMedGoogle Scholar
• 19 Hill JR. A kinship survey of cancer in the Utah Mormon population.  , Ph.D. Thesis, University of Utah, Salt Lake City, Utah, 1980; 
  PubMedGoogle Scholar
• 20 Hill JR. A survey of cancer sites by kinship in the Utah Mormon population. In: Cairns J, Lyon JL, Skolnick M (eds). Cancer Incidence in Defined Populations, Banbury Report No.4 New York: Cold Spring Harbor Laboratory Press 1980: 299-318
  Google Scholar
• 21 Hirschhorn JN. Genetic epidemiology of type 1 diabetes.  Pediatric Diabetes. 2003;  4 87-100
  CrossrefPubMedGoogle Scholar
• 22 Intermountain Healthcare . , Annual report 2004. Available from http://intermountainhealthcare.org/xp/public/ , Accessed 02 February 2006
• 23 Jorde LB, Carey JC, Bamshad MJ, White RL. Medical Genetics. 2nd ed. Mosby 1999
• 24 Kamb A, Shattuck-Eidens D, Eeles R, Liu Q, Gruis NA, Ding W, Hussey C, Tran T, Miki Y, Weaver-Feldhaus J, MacClure M, Aitken JF, Anderson DE, Bergman W, Frants R, Goldgar DE, Green A, MacLennan R, Martin NG, Meyer LJ, Youl P, Zone JJ, Skolnick MH, Cannon-Albright LA. Analysis of the p16 gene (CDKN2) as a candidate for the chromosome 9p melanoma susceptibility locus.  Nature Genetics. 1994;  8 22-26
  CrossrefPubMedGoogle Scholar
• 25 Karter AJ, Rowell SE, Ackerson LM, Mitchell BD, Ferrara A, Selby JV, Newman B. Excess maternal transmission of type 2 diabetes the northern california kaiser permanente diabetes registry.  Diabetes Care. 1999;  22 938-943
  CrossrefPubMedGoogle Scholar
• 26 Li H, Isomaa B, Taskinen MR, Groop L, Tuomi T. Consequences of a family history of type 1 and type 2 diabetes on the phenotype of patients with type 2 diabetes.  Diabetes Care. 2000;  23 589-594
  CrossrefPubMedGoogle Scholar
• 27 Li H, Lindholm E, Almgren P, Gustafsson A, Forsblom C, Groop L, Tuomi T. Possible human leukocyte antigen-mediated genetic interaction between type 1 and type 2 Diabetes.  J Clin Endocrinol Metab. 2001;  86 574-582
  PubMedGoogle Scholar
• 28 Lorenzen T, Pociot F, Stilgren L, Kristiansen OP, Johannesen J, Olsen PB, Walmar A, Larsen A, Albrechtsen NC, Eskildsen PC, Andersen OO, Nerup J. The Danish IDDM Epidemiology, and Genetics Group . Predictors of iddm recurrence risk in offspring of Danish iddm patients.  Diabetologia. 1998;  41 666-673
  CrossrefPubMedGoogle Scholar
• 29 Malécot G. Les Mathématiques de l’Hérédité. Paris: Masson et Cie 1948
• 30 Medici F, Hawa M, Ianari A, Pyke DA, Leslie RDG. Concordance rate for type 2 diabetes mellitus in monozygotic twins: actuarial analysis.  Diabetologia. 1999;  42 146-150
  CrossrefPubMedGoogle Scholar
• 31 MacCarthy M. The genetics of type 2 diabetes: the consequences of complexity.  GeneScreen. 2000;  1 81-84
  CrossrefPubMedGoogle Scholar
• 32 MacCarthy M, Cassell P, Tran T, Mathias L, t Hart LM, Maassen JA, Snehalatha C, Ramachandran A, Viswanathan M, Hitman GA. Evaluation of the importance of maternal history of diabetes and of mitochondrial variation in the development of niddm.  Diabetic Medicine. 1996;  13 420-428
  CrossrefPubMedGoogle Scholar
• 33 MacLellan T, Jorde L, Skolnick M. Genetic distances between the utah mormons and related populations.  Am J Hum Genet. 1984;  36 836-837
  PubMedGoogle Scholar
• 34 Meigs JB, Cupples LA, Wilson PWF. Parental transmission of type 2 diabetes the framingham offspring study.  Diabetes. 2000;  49 2201-2207
  CrossrefPubMedGoogle Scholar
• 35 Miki Y, Swensen J, Shattuck-Eidens D, Futreal PA, Harshman K, Tavtigian S, Lui Q, Cochran C, Bennett LM, Ding W, Bell R, Rosenthal J, Hussey C, Tran T, MacClure M, Frye C, Hattier T, Phelps R, Haugen-Strano A, Katcher H, Yakumo K, Gholami Z, Shaffer D, Stone S, Bayer S, Wray C, Bogden R, Dayananth P, Ward J, Tonin P, Narod S, Bristow PK, Norris FH, Helvering L, Morrison P, Rosteck P, Lai M, Barrett JC, Lewis C, Neuhausen S, Cannon-Albright LA, Goldgar D, Wiseman R, Kamb A, Skolnick MH. A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1.  Science. 1994;  266 66-71
  CrossrefPubMedGoogle Scholar
• 36 Mitchell BD, Kammerer CM, Reinhart LJ, Stern MP, MacCluer JW. Is there an excess in maternal transmission of niddm?.  Diabetologia. 1995;  38 314-317
  PubMedGoogle Scholar
• 37 Mitchell BD, Valdex R, Hazuda HP, Haffner SM, Monterrosa A, Stern MP. Differences in the prevalence of diabetes and impaired glucose tolerance according to maternal or paternal history of diabetes.  Diabetes Care. 1993;  16 1262-1267
  CrossrefPubMedGoogle Scholar
• 38 National Institute of Diabetes and Digestive and Kidney Diseases . , National Diabetes Statistics fact sheet: general information and national estimates on diabetes in the United States, U.S. Department of Health and Human Services, National Institute of Health, Bethesda (MD), 2005. Available from http://diabetes.niddk.nih.gov/dm/pubs/statistics/index.htm , Accessed 02 December, 2005
• 39 National Committee for Quality Assurance: HEDIS 2006 .Health plan employer data and information set. Volume 2: Technical specifications. Washingtion, DC: National Committee for Quality Assurance 2005
• 40 National Committee for Quality Assurance NCQA Programs: HEDIS . , Available from: http://www.ncqa.org/Programs/HEDIS/ , Accessed 10 January, 2006
• 41 Office of Public Health Assessment . , Local health district overview report (2003-2004 Utah Health Status Survey Report). Utah Department of Health, Salt Lake City (UT), 2005. Available from http://health.utah.gov/opha/publications/2003hss/lhd/03-04HSS_LHD_COMPLETE.pdf , Accessed 19 April, 2006
• 42 Quatraro A, Consoli G, Ceriello A, Giugliano D. Heterogeneity of diabetes mellitus.  Diabetologia. 1987;  30 678-679
  PubMedGoogle Scholar
• 43 Raffel LJ, Rotter JI. Type 1 diabetes mellitus. In: King A, Rotter JI, Motulsky AG (eds). The Genetics Basis of Common Disease. New York: Oxford University Press 2002: 431-456
  Google Scholar
• 44 Redondo MJ, Fain PR, Eisenbarth GS. Genetics of type 1a diabetes.  Recent Progress in Hormone Research. 2001;  56 69-90
  CrossrefPubMedGoogle Scholar
• 45 Rich SS, Panter SS, Goetz FC, Hedlund B, Barbosa J. Shared genetic susceptibility of type 1 (insulin-dependent) and type 2 (non-insulin- dependent) diabetes mellitus: contribution of HLA and haptoglobin.  Diabetologia. 1991;  34 350-355
  CrossrefPubMedGoogle Scholar
• 46 Riley MD, Blizzard CL, MacCarty DJ, Senator GB, Dwyer T, Zimmet P. Parental history of diabetes in an insulin-treated diabetes registry.  Diabetic Medicine. 1997;  14 35-41
  PubMedGoogle Scholar
• 47 Skolnick M. The utah genealogical data base: A resource for genetic epidemiology. In: Cairns J, Lyon JL, Skolnick M (eds). Cancer Incidence in Defined Populations, Banbury Report No.4 New York: Cold Spring Harbor Laboratory Press 1980: 285-297
  Google Scholar
• 48 Sveinbjornsdottir S, Hicks AA, Jonsson T, Petursson H, Gugmundsson G, Frigge ML, Kong A, Gulcher JR, Stefansson K. Familial aggregation of parkinson's disease in iceland.  N Engl J Med. 2000;  343 1765-1770
  CrossrefPubMedGoogle Scholar
• 49 Tavtigian SV, Simard J, Teng DHF, Abtin V, Baumgard M, Beck A, Camp NJ, Carillo AR, Chen Y, Dayananth P, Desrochers M, Dumont M, Farnham JM, Frank D, Frye C, Ghaffari S, Gupte JS, Hu R, Iliev D, Janecki T, Kort EN, Laity KE, Leavitt A, Leblanc G, MacArthur-Morrison J, Pederson A, Penn B, Peterson KT, Reid JE, Richards S, Schroeder M, Smith R, Snyder SC, Swedlund B, Swensen J, Thomas A, Tranchant M, Woodland AM, Labrie F, Skolnick MH, Neuhausen S, Rommens J, Cannon-Albright LA. A candidate prostate cancer susceptibility gene at chromosome 17p.  Nature Genetics. 2001;  27 172-180
  PubMedGoogle Scholar
• 50 Tillil H, Köbberling J. Age-corrected empirical genetic risk estimates for first-degree relatives of IDDM patients.  Diabetes. 1987;  36 93-99
  CrossrefPubMedGoogle Scholar
• 51 Utah Resource for Genetic and Epidemiology Research . , RGE: Utah Resource for Genetic and Epidemiologic Research. Utah Resource for Genetic and Epidemiology Research, 2005. Available from http://www.research.utah.edu/rge/ , Accessed 02 March, 2006
• 52 Utah Governor's Office of Planning and Budget . , Notes on the economic 2006. Economic Summary. Governor's Office of Planning and Budget, 2006. Available from http://www.governor.utah.gov/dea , Accessed 08 June, 2006
• 53 Wagener DK, Sacks JM, LaPorte RE, Macgregor JM. The Pittsburgh study of insulin-dependent diabetes mellitus. Risk for diabetes among relatives of IDDM.  Diabetes. 1982;  31 136-144
  CrossrefPubMedGoogle Scholar
• 54 Warram JH, Krolewski AS, Gottlied MS, Kahn CR. Differences in risk of insulin-dependent diabetes in offspring of diabetic mothers and diabetic fathers.  N Engl J Med. 1984;  311 149-152
  PubMedGoogle Scholar
• 55 Wylie JE, Mineau GP. Biomedical databases: protecting privacy and promoting research.  TRENDS in Biotechnology. 2003;  21 113-116
  CrossrefPubMedGoogle Scholar

Correspondence

Dipl. Inform. Med. M. B. Weires

Department of Medical Informatics

University of Heidelberg

Im Neuenheimer Feld 400

69120 Heidelberg

Germany

Phone: +49/6221/56 74 83

Fax: +49/6221/56 49 97

Email: m.weires@dkfz.de