Skip to main content
Log in

Maternal diabetes mellitus - early consequences for the offspring

  • Original Article
  • Published:
Pediatric Nephrology Aims and scope Submit manuscript

Abstract

Although several studies have focused on the effects of nutritional status during intrauterine development, few have addressed the impact of maternal diabetes mellitus on renal function and morphology in the young offspring. In the present study, renal morpho-functional aspects were studied in the offspring of diabetic rats. Diabetes was induced in female rats with a single dose of streptozotocyn (STZ), 10 days before mating. After weaning, the offspring (DO) had free access to food and water. Arterial blood pressure was measured, by tail plethysmography, from 2 months on. Renal function was evaluated in 2- and 3-month-old rats in the DO group and in controls (C). Analysis of renal morphology was carried out in newborn and in 1-, 2- and 3-month-old rats in both groups. Although the nephron number was not changed in the DO group, glomerular hypertrophy was observed from 2 months on. At the same age, the glomerular filtration rate was significantly reduced in DO, and blood pressure was significantly increased, when compared to C. Glucose tolerance test (GTT) from DO showed a different profile when compared to C. The number of PCNA positive cells in renal tissue was similar in both groups. Our data suggests that exposure to intrauterine diabetes may be an important cause of both impaired renal function and hypertension in offspring, without changes in the nephron number.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Barker DJ, Osmond C, Golding J, Kuh D, Wadsworth ME (1989) Growth in utero, blood pressure in childhood and adult life and mortality from cardiovascular disease. BMJ 298:564–567

    Article  CAS  Google Scholar 

  2. Barker DJ (1995) Fetal origins of coronary heart disease. BMJ 311:171–174

    Article  CAS  Google Scholar 

  3. Campbell DM, Hall MH, Barker DJ, Cross J, Shiell AW, Godfrey KM (1996) Diet in pregnancy and the offspring’s blood pressure 40 years later. Br J Obstet Gynaecol 103:273–280

    Article  CAS  Google Scholar 

  4. Barker DJ (1998) In utero programming of chronic disease. Clin Sci 95:115–128

    Article  CAS  Google Scholar 

  5. Pedersen L, Tygstrup I, Pedersen J (1964) Congenital malformations in newborn infants of diabetic women. Lancet 13:1124–1126

    Article  Google Scholar 

  6. Martinez-Frias ML (1994) Epidemiological analysis of outcomes of pregnancy in diabetic mothers:identification of the most frequent congenital anomalies. Am J Med Gen 51:108–113

    Article  CAS  Google Scholar 

  7. Travers J, Pratten M, Beck F (1989) Effects of low insulin levels on rat embryonic growth and development. Diabetes 38:773–778

    Article  CAS  Google Scholar 

  8. Amri K, Freund N, Vilar J, Merlet-Benichou C, Lelièvre-Pegorier M (1999) Adverse effects of hyperglycemia on kidney development in rats. Diabetes 48:2240–2245

    Article  CAS  Google Scholar 

  9. Hoy WE, Rees M, Kile E, Mathews JD, Wang Z (1999) A new dimension to the Barker hypothesis: low birth weight and susceptibility to renal disease. Kidney Int 56:1072–1077

    Article  CAS  Google Scholar 

  10. Rocha SO, Gomes GN, Forti ALL, Franco MCP, Fortes ZB, Cavanal MF, Gil FZ (2005) Long-term effects of maternal diabetes on vascular reactivity and renal function in rat male offspring. Pediatr Res 58:1274–1279

    Article  Google Scholar 

  11. Brenner BM, Cheetow GM (1994) Congenital oligonephropathy and the etiology of adult hypertension and progressive renal injury. Am J Kidney Dis 23:171–175

    Article  CAS  Google Scholar 

  12. Brenner BM, Garcia DL, Anderson S (1988) Glomeruli and blood pressure. Less of one, more of the other? Am J Hypertension 1:335–347

    Article  CAS  Google Scholar 

  13. Lucas SR, Zaladek Gil F, Costa Silva VL, Miraglia SM (1991) Functional and morphometric evaluation of intrauterine under-nutrition on kidney development of the progeny. Braz J Med Biol Res 24:967–970

    CAS  PubMed  Google Scholar 

  14. Lucas SR, Miraglia SM, Zaladek Gil F, Coimbra TM (2001) Intrauterine food restriction as a determinant of nephrosclerosis. Am J Kidney Dis 37:467–476

    Article  Google Scholar 

  15. Malavazi AG, Barão MA, Gomes GN, Odo LN, Franco MC, Nigro D, Lucas SR, Laurindo FR, Brandizzi LI, Zaladek Gil F (2002) L-arginine effects on blood pressure and renal function of intrauterine restricted rats. Pediatr Nephrol 17:856–862

    Article  Google Scholar 

  16. Gil FZ, Lucas SR, Gomes GN, Cavanal MF, Coimbra TR (2005) Effects of intrauterine food restriction and long-term dietary supplementation with L-arginine on age-related changes in renal function and structure of rats. Pediatr Res 57:724–731

    Article  CAS  Google Scholar 

  17. Nascimento-Gomes G, Zaladek Gil F, Mello-Aires M (1997) Alterations of the renal handling of H+ in diabetic rats. Kidney Blood Press Res 20:251–257

    Article  CAS  Google Scholar 

  18. Franco MC, Akamine EH, Di Marco GS, Casarini DE, Fortes ZB, Tostes RC, Carvalho MH, Nigro D (2003) NADPH oxidase and enhanced superoxide generation in intrauterine undernourished rats: involvement of the renin-angiotensin system. Cardiovasc Res 59:767–775

    Article  CAS  Google Scholar 

  19. Nold JL, Georgieff MK (2004) Infants of diabetic mothers. Pediatr Clin North Am 51:619–637

    Article  Google Scholar 

  20. Carey AV, Carey RM, Gomez RA (1992) Expression of alpha smooth muscle actin in the developing kidney vasculature. Hypertension 19(suppl II):168–175

    Google Scholar 

  21. Hall PA, Levison DA, Woods AL, Yu CC, Kellock DB, Watkins JA, Barnes DM, Gillett CE, Camplejohn R, Dover R (1990) Proliferating cell nuclear antigen (PCNA) immunolocalization in paraffin sections: the index of cell proliferation with evidence of deregulated expression in some neoplasms. J Pathol 162:285–294

    Article  CAS  Google Scholar 

  22. Srinivasan M, Aalinkeel R, Song F, Patel MS (2003) Programming of islet functions in the progeny of hyperinsulinemic/obese rats. Diabetes 52:984–990

    Article  CAS  Google Scholar 

  23. Marcantoni C, Jafar TH, Oldrizzi L, Levey AS, Maschio G (2000) The role of systemic hypertension in the progression of nondiabetic renal disease. Kidney Int Suppl 75:S44–S48

    Article  CAS  Google Scholar 

  24. Tolbert EM, Weisstuch J, Feiner HD, Dworkin LD (2000) Onset of glomerular hypertension with aging precedes injury in the spontaneously hypertensive rat. Am J Physiol Renal Physiol 278:F839–F846

    Article  CAS  Google Scholar 

  25. Moeller I, Allen AM, Chai SY, Zhuo J, Mendelsohn FA (1998) Bioactive angiotensin peptides. J Hum Hypertens 12:289–293

    Article  CAS  Google Scholar 

  26. Lemos VS, Silva DM, Walther T, Alenina N, Bader M, Santos RA (2005) The endothelium-dependent vasodilator effect of the nonpeptide Ang(1–7) mimic AVE 0991 is abolished in the aorta of mas-knockout mice. J Cardiovasc Pharmacol 46:274–279

    Article  CAS  Google Scholar 

  27. Li P, Chappell MC, Ferrario CM, Brosnihan KB (1997) Angiotensin-(1–7) augments bradykinin-induced vasodilation by competing with ACE and releasing nitric oxide. Hypertension 29:394–400

    Article  CAS  Google Scholar 

  28. Woods LL, Weeks DA, Rasch R (2001) Hypertension after neonatal uninephrectomy in rats precedes glomerular damage. Hypertension 38:337–342

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This study was supported by FAPESP (Fundação de Amparo à Pesquisa do Estado de São Paulo) and CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico, Brazil).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Guiomar Nascimento Gomes.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Magaton, A., Gil, F.Z., Casarini, D.E. et al. Maternal diabetes mellitus - early consequences for the offspring. Pediatr Nephrol 22, 37–43 (2007). https://doi.org/10.1007/s00467-006-0282-4

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00467-006-0282-4

Keywords

Navigation