Summary
Both non-insulin-dependent diabetes mellitus and diabetic nephropathy show familial aggregation. If diabetes and renal disease have independent determinants (genetic or otherwise), offspring of parents with diabetic renal disease should have a similar risk of diabetes to those offspring of parents with diabetes alone. To test this hypothesis, the prevalence of diabetes was examined in a population-based pedigree study in Pima Indian offspring of three mutually exclusive parental types: 1) diabetic with renal disease, 2) diabetic, but without renal disease and 3) non-diabetic. Among offspring of one diabetic parent and one non-diabetic parent (n=320) the prevalence of diabetes at ages 15–24 years and 25–34 years was 0% and 11%, respectively if the diabetic parent did not have renal disease compared with 6% and 28% respectively if the diabetic parent did have renal disease. Corresponding rates for offspring of two diabetic parents (n=121) were 10% and 17%, respectively if neither parent had renal disease compared with 30% and 50%, respectively if one parent did have renal disease. The presence of renal disease in a parent with diabetes relative to diabetes alone was associated with 2.5 times the odds of diabetes (95% confidence interval 1.4–4.3) in the offspring controlled for age, age at onset of parental diabetes and diabetes in the other parent using logistic regression. These findings provide support for parental diabetic renal disease, independent of age at onset of parental diabetes, conferring an increased risk for diabetes in the offspring. The results are compatible with the hypothesis that the susceptibility to renal disease in the parents and to diabetes in the offspring are due to shared familial environmental factors or to the same gene or set of genes.
Article PDF
Similar content being viewed by others
Abbreviations
- NIDDM:
-
Non-insulin-dependent diabetes mellitus
- ESRD:
-
end-stage renal disease
References
Rimoin DL (1972) Inheritance in diabetes mellitus. Med Clin N Am 55: 807–819
Köbberling J, Tillil H, Lorenz HJ (1985) Genetics of type 2A- and type 2B-diabetes mellitus. Diabetes Res Clin Pract ii: [Suppl] 1: S311 (Abstract)
Lee ET, Anderson PS, Bryan J, Bahr C, Coniglione T, Cleves M (1985) Diabetes, parental diabetes and obesity in Oklahoma Indians. Diabetes Care 8: 107–113
Viswanathan M, Mohan V, Snehalatha C, Ramachandran A (1985) High prevalence of type 2 (non-insulin-dependent) diabetes among offspring of conjugal type 2 diabetic parents in India. Diabetologia 28: 907–910
Knowler WC, Pettitt DJ, Saad MF, Bennett PH (1990) Diabetes mellitus in the Pima Indians: incidence, risk factors and pathogenesis. Diabetes Metab Rev 6: 1–27
Knowler WC, Pettitt DJ, Savage PJ, Bennett PH (1981) Diabetes incidence in Pima Indians: contributions of obesity and parental diabetes. Am J Epidemiol 113: 144–156
Seaquist ER, Goetz FC, Rich S, Barbosa J (1989) Familial clustering of diabetic kidney disease: evidence for genetic susceptibility to diabetic nephropathy. New Engl J Med 320: 1161–1165
Pettitt DJ, Saad MF, Bennett PH, Nelson RG, Knowler WC (1990) Familial predisposition to renal disease in two generations of Pima Indians with type 2 (non-insulin-dependent) diabetes mellitus. Diabetologia 33: 438–443
Knowler WC, Pettitt DJ, Bennett PH, Williams RC (1983) Diabetes mellitus in the Pima Indians: genetic and evolutionary considerations. Am J Phys Anthropol 62: 107–114
Knowler WC, Savage PJ, Nagulesparan M et al. (1982) Obesity, insulin resistance and diabetes mellitus in the Pima Indians. In: Köbberling JM, Tattersall R (eds) The genetics of diabetes mellitus. Serono Symposium No. 47 Academic Press, London, pp 243–250
Knowler WC, Pettitt DJ, Lillioja S, Nelson RG (1988) Genetic and environmental factors in the development of diabetes mellitus in the Pima Indians. In: Smith U, Eriksson S, LindgÄrde F (eds) Genetic susceptibility to environmental factors — a challenge for public intervention. Almqvist and Wiksell International, Stockholm pp 67–84
Knowler WC, Bennett PH, Hamman RF, Miller M (1978) Diabetes incidence and prevalence in Pima Indians: 19-fold greater incidence than in Rochester Minnesota. Am J Epidemiol 108: 497–505
Bennett PH, Burch TA, Miller M (1971) Diabetes mellitus in American (Pima) Indians. Lancet II: 825–828
WHO Study Group. (1985) Diabetes mellitus. World Health Organization, Geneva pp 9–17 (Tech Rep Ser 727)
Shevsky MC, Stafford DD (1923) A clinical method for the estimation of protein in urine and other body fluids. Arch Intern Med 32: 222–225
Chasson AL, Grady HJ, Stanley MA (1961) Determination of creatinine by means of automatic chemical analysis. Am J Clin Pathol 35: 83–88
Ginsberg JM, Chang BS, Matarese RA, Garella S (1983) Use of single voided urine samples to estimate quantitative proteinuria. New Engl J Med 309: 1543–1546
Shaw AB, Risdon P, Lewis-Jackson JD (1983) Protein creatinine index and Albustix in assessment of proteinuria. BMJ 287: 929–932
Nelson RG, Newman JM, Knowler WC et al. (1988) Incidence of end-stage renal disease in type 2 (non-insulin-dependent) diabetes mellitus in Pima Indians. Diabetologia 31: 730–736
Kleinbaum DG, Kupper LL, Morgenstern H (1982) Epidemiologic research: principles and quantitative methods. Van Nostrand Reinhold, New York, Berkshire, Melbourne, Ontario, 419–446
S. A. G. E. Statistical Analysis for Genetic Epidemiology, Release 2.1. (1992) Computer program package. Department of Biometry and Genetics, LSU Medical Center, New Orleans
Kunzelman CL, Knowler WC, Pettitt DJ, Bennett PH (1989) Incidence of proteinuria in type 2 diabetes mellitus in the Pima Indians. Kidney Int 35: 681–687
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
McCance, D.R., Hanson, R.L., Pettitt, D.J. et al. Diabetic nephropathy: a risk factor for diabetes mellitus in offspring. Diabetologia 38, 221–226 (1995). https://doi.org/10.1007/BF00400098
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00400098