Skip to main content
SpringerLink
Log in

Low IGF-1 levels are associated with cardiovascular risk factors in haemodialysis patients

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

Cardiovascular diseases (CVD) constitute a significant risk and may, in part, explain the high morbidity and mortality rates among haemodialysis (HD) patients. Several studies have implicated reduced insulin like growth factor (IGF-1) levels in the development of CVD. However, it is not clear whether IGF-1, and its relationship with other hormones such as leptin, insulin, and growth hormone (GH), as well as anthropometric variables may explain the high incidence of vascular complications in chronic kidney disease (CKD) patients. This study was designed to measure total serum IGF-1, leptin, insulin and GH levels in CKD patients and in age-matched control subjects and to elucidate the relationship between IGF-1 and GH, leptin, and insulin as well as other known aetiological risk factors for CVD including blood pressure, body mass index (BMI), and age. The study consisted of 50 CKD patients [36 M and 14 F; mean age; 41.8 ± 10.3 years) on maintenance haemodialysis and 50 healthy control subjects (36 M and 14 F; mean age 41.6 ± 10.2 years) matched for age and sex. None of the subject among patients and controls reported either smoking or history of diabetes mellitus. The circulating levels of IGF-1 were significantly lower (P < 0.001) in both male and female patients compared to the control subjects. Moreover, IGF-1 was strongly and inversely correlated with both systolic blood pressure (SBP) (r = −0.360; P < 0.01) and diastolic blood pressure (DBP) (r = −0.512; P < 0.001) in the CKD group, and when the two groups were combined SBP (r = −0.396; P < 0.001) and DBP (r = −0.296; P < 0.01). When adjusted for age, the correlation was more significant, however, when adjusted for BMI no significant correlation was observed between IGF-1 and blood pressure. IGF-1 was inversely correlated with age (r = −0.367; P < 0.01) and BMI (r = −0.310; P < 0.05) in the control group, but not the patient group. In controls and patients, respectively, a positive correlation between leptin and BMI (r = 0.358; P < 0.01; r = 0.640, P < 0.001) was observed. The results show that circulating levels of IGF-1 were significantly lower in CKD patients as compared to healthy normal subjects and were inversely correlated with SBP and DBP independent of age, but not BMI indicative of a strong relationship between cardiovascular risk factors and low IGF-1 levels. Although, the data do not clearly indicate low IGF-1 levels as a cause or an effect of these cardiovascular risk factors, they do point to an interesting relationship between low IGF-1 levels and increased cardiovascular risk factors among CKD patients as compared to age-matched healthy control subjects.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Qureshi AR, Alvestrand A, Divino-Filho JC, Gutierrez A, Heimburger O, Lindholm B, Bergstrom J (2002) Inflammation, malnutrition, and cardiac disease as predictors of mortality in hemodialysis patients. J Am Soc Nephrol 13:S28–S36

    PubMed  Google Scholar 

  2. de Mutsert R, Krediet RT (2006) Malnutrition, inflammation and atherosclerosis (MIA-syndrome) in dialysis patients. Ned Tijdschr Geneeskd 150:2023–2027

    PubMed  Google Scholar 

  3. Laron Z, Wang XL, Klinger B, Silbergeld A, Davidovits M, Eisentein Wilcken D (1996) Growth hormone treatment increase circulating lipoproteins in children with chronic renal failure. J Pediatr Endocrinol Metab 9:533–537

    PubMed  CAS  Google Scholar 

  4. Owen WF, Madore F, Brenner BM (1996) An observational study of cardiovascular characteristics of long-term end-stage renal disease survivors. Am J Kidney Dis 28:931–936

    PubMed  CAS  Google Scholar 

  5. Goldsmith DJ, Covic AC, Venning MC, Ackrill P (1997) Ambulatory blood pressure monitoring in renal dialysis and transplant patients. Am J Kidney Dis 29:593–600

    PubMed  CAS  Google Scholar 

  6. Kohlhagen J, Kelly J (2003) Prevalence of vascular risk factors and vascular disease in predialysis chronic renal failure. Nephrology 8:274–279

    Article  PubMed  Google Scholar 

  7. Covic A, Gusbeth-Tatomir P, Goldsmith D (2003) The challenge of cardiovascular risk factors in end stage renal disease. J Nephrol 16:476–486

    PubMed  Google Scholar 

  8. Paoletti E, Specchia C, Di Maio G, Bellino D, Damasio B, Cassottana P, Cannella G (2004) The worsening of left ventricular hypertrophy is the strongest predictor of sudden cardiac death in haemodialysis patients: a 10-year survey. Nephrol Dial Transplant 19:1829–1834

    Article  PubMed  Google Scholar 

  9. Ferns GA, Morani AS, Anggard EE (1991) The insulin-like growth factors: their putative role in atherosgenesis. Artery 18:197–225

    PubMed  CAS  Google Scholar 

  10. Janssen JA, Stolk RP, Pols HA (1998) Serum free IGF-I, total IGF-I, IGFBP-1 and IGFBP-3 levels in an elderly population: relation to age and sex steroid levels. Clin Endocrinol 48:471–478

    Article  CAS  Google Scholar 

  11. Harrela M, Koistinen R, Tuomilehto J, Nissinen A, Seppala M (2000) Low serum insulin-like growth factor-binding protein-1 is associated with an unfavourable cardiovascular risk profile in elderly men. Ann Med 32:424–428

    PubMed  CAS  Google Scholar 

  12. Juul A, Scheike T, Davidsen M, Gyllenborg J, Jorgensen T (2002) Low serum insulin-like growth factor-1 is associated with increased risk of ischemic heart disease: a population-based study case control. Circulation 106:939–944

    Article  PubMed  CAS  Google Scholar 

  13. Laughlin GA, Barret- Conner E, Criqui MH, Kritz-Silverstein D (2004) The prospective association of serum insulin-like growth factor-1 and IGF-binding protein-1 levels with all cause and cardiovcascular disease mortality in older adults: the rancho Bernardo Study. J Clin Endocrinol Metab 89:114–120

    Article  PubMed  CAS  Google Scholar 

  14. Laviades C, Gil MJ, Monreal I, Gonzalez A, Diez J (1997) Is the tissue availability of circulating insulin-like growth factor involved in orhgan damage and glucose regulation in hypertension? J Hypertension 15:1159–1165

    Article  CAS  Google Scholar 

  15. Van den Brande JL, Hoogerbrugge CM, Beyreuther K, Roepstorff P, Jansen J, van Buul-Offers SC (1990) Isolation and partial characterization of IGF-like peptides from Cohn fraction IV of human plasma. Acta Endocrinol (Copenh) 122:683–695

    Google Scholar 

  16. Mathews LS, Norstedt G, Palmiter RD (1986) Regulation of insulin-like growth factor I gene expression by growth hormone. Proc Natl Acad Sci USA 83:9343–9347

    Article  PubMed  CAS  Google Scholar 

  17. Radosavljevic T, Todorovic V, Vucevic D, Sikic B (2005) The growth hormone axis and insulin-like growth factors. Med Pregl 58:558–562

    Article  PubMed  Google Scholar 

  18. Raile K, Klammt J, Schneider A, Keller A, Laue S, Smith R, Pfaffle R, Kratzsch J, Keller E, Kiess W (2006) Clinical and functional characteristics of the human Arg59Ter insulin-like growth factor 1 receptor (IGF1R) mutation: implications for a gene dosage effect of the human IGF1R. J Clin Endocrinol Metab doi:10.1210/jc

  19. Szczech LA, Reddan DN, Klassen PS, Coladonato J, Chua B, Lowrie EG, Lazarus JM, Owen WF Jr (2003) Interactions between dialysis-related volume exposures, nutritional surrogates and mortality among ESRD patients. Nephrol Dial Transplant 18:1585–1591

    Article  PubMed  Google Scholar 

  20. Fouque D, Juillard L, Lasne Y, Tabakian A, Laville M, Joly MO, Laville M (1998) Acute leptin regulation in end-stage renal failure: the role of growth hormone and IGF-1. Kidney Int 54:932–937

    Article  PubMed  CAS  Google Scholar 

  21. Rodriguez-Carmona A, Perez Fontan M, Cordido F, Garcia Falcon T, Garcia-Buela J (2000) Hyperleptinemia is not correlated with markers of protein malnutrition in chronic renal failure: a cross-sectional study in predialysis, peritoneal dialysis and hemodialysis patients. Nephron 86:274–280

    Article  PubMed  CAS  Google Scholar 

  22. Rouche F, Westermann F, Englaro P, Blum WF, Schonau E (1998) Serum leptin is suppressed by growth hormone therapy in growth hormone-deficient children. Horm Res 50:18–21

    Article  Google Scholar 

  23. Patel L, Webb NJ, Bradbury MG, Zaman N, Smith P, Lewis MA Postlethwaite RJ, Price DA, Clayton PE (2002) Serum leptin and IGF-I during growth hormone treatment in chronic renal failure. Pediatr Nephrol 17:643–647

    Article  PubMed  Google Scholar 

  24. Fervenza FC, Friedlaender MM, Ike JO, Rabkin R (1998) Insulin-like growth factor-I treatment to enhance renal function in advanced chronic renal failure. Ren Fail 20:349–356

    Article  PubMed  CAS  Google Scholar 

  25. Frystyk J, Ivarsen P, Skjaerbaek C, Flyvbjerg A, Pedersen EB, Orskov H (1999) Serum-free insulin-like growth factor I correlates with clearance in patients with chronic renal failure. Kidney Int 56:2076–2084

    Article  PubMed  CAS  Google Scholar 

  26. Obineche EN, Gillett PT, Abdulle AM, Sulaiman MN, Rokhaimi MA (2002) Leptin, lipid and lipid metabolism-related hormones in Chronic kidney disease in Arabia. Nephrology 7:115–120

    Article  CAS  Google Scholar 

  27. Burkhard Tönshoff, Daniela Kiepe, Sonia Ciarmatori (2005) Growth hormone/insulin-like growth factor system in children with chronic renal failure. Pediatr Nephrol 20:279–289

    Article  PubMed  Google Scholar 

  28. Haffner D, Blum W, Heinrich U, Mehls O, Tönshoff B (1997) Impaired Postprandial Regulation of Insulin-Like Growth Factor Binding Protein-1in Children with Chronic Renal Failure. J Clin Endocrinol Metab 82:2832–2835

    Article  PubMed  CAS  Google Scholar 

  29. Burch WM, Correa J, Shively JE, Powell DR (1990) The 25 kilodalton insulin-like growth factor (IGF)-binding protein inhibits both basal and IGF-mediated growth of chick embryo pelvic cartilage in vitro. J Clin Endocrinol Metab 70:173–180

    PubMed  CAS  Google Scholar 

  30. Lewitt MS, Denyer GS, Cooney GJ, Baxter RC (1991) Insulin-like growth factor binding protein-1 modulates blood glucose levels. Endocrinology 129:2254–2256

    Article  PubMed  CAS  Google Scholar 

  31. Benbassat CA, Maki KC, Unterman TG (1997) Circulating levels of insulin-like growth factor (IGF) binding protein-1 and -3 in ageing men: relationships to insulin, glucose, IGF, and dehydroepiandrosterone sulfate levels and anthropometric measures. J Clin Endocrinol Metab 82:1484–1491

    Article  PubMed  CAS  Google Scholar 

  32. Powell DR, Suwanichkul A, Cubbage ML, DePaolis LA, Snuggs MB, Lee PD (1991) Insulin inhibits transcription of the human gene for insulin-like growth factor-binding protein-1. J Biol Chem 266:18868–18876

    PubMed  CAS  Google Scholar 

  33. Wheatcroft SB, Kearney MT, Shah AM, Grieve DJ, Williams IL, Miell JP, Crossey PA (2003) Vascular endothelial function and blood pressure homeostasis in mice overexpressing IGF binding protein-1. Diabetes 52:2075–2082

    Article  PubMed  CAS  Google Scholar 

  34. Watanabe T, Itokawa M, Nakagawa Y, Iguchi T, Katagiri T (2003) Increased levels of insulin-like growth factor binding protein-3 in hypertensive patients with carotid atherosclerosis. Am J Hypertens 16:754–760

    Article  PubMed  CAS  Google Scholar 

  35. Kurbanov RD, Eliseeva MR, Tursunov RR, Kurbanova DR, Zakirova FA (2003) Humoral markers of endothelial dysfunction in essential hypertension. Kardiologiia 43:61–64

    Google Scholar 

  36. Landin-Wilhelmsen K, Wilhelmsen L, Lappas G (1994) Serum insulin-like growth factor I in a random population sample of men and women: relation to age, sex, smoking habits, coffee consumption and physical activity, blood pressure and concentrations of plasma lipids, fibrinogen, parathyroid hormone and osteocalcin. Clin Endocrinol 41:351–357

    CAS  Google Scholar 

  37. Holmes MD, Pollak MN, Hankinson SE (2002) Lifestyle Correlates of Plasma Insulin-like Growth Factor I and Insulin-like Growth Factor Binding Protein 3 Concentrations. Cancer Epidemiol Biomark Prev 11:862–867

    CAS  Google Scholar 

  38. Teramukai S, Rohan T, Eguchi H, Oda T, Shinchi K, Kono S (2002) Anthropometric and Behavioral Correlates of Insulin-like Growth Factor I and Insulin-like Growth Factor Binding Protein 3 in Middle-aged Japanese Men. Am J Epidemiol 156:344–348

    Article  PubMed  Google Scholar 

  39. Goodman-Gruen D, Barrett-Connor E (1997) Epidemiology of insulin-like growth factor-I in elderly men and women. The Rancho Bernardo Study. Am J Epidemiol 145:970–976

    PubMed  CAS  Google Scholar 

  40. Harris T, Kiel D, Roubenoff R, Langlois J, Hannan M, Havlik R (1997) Association of insulin-like growth factor-I with body composition, weight history, and past health behaviors in the very old: The Framingham Heart Study. J Am Geriatr Soc 45:133–139

    PubMed  CAS  Google Scholar 

  41. Johanson AJ, Blizzard RM (1981) Low somatomedin-C levels in older men rise in response to growth hormone administration. Johns Hopkins Med J 149:115–117

    PubMed  CAS  Google Scholar 

  42. Sonksen PH, Cuneo RC, Salomon F, McGauley G, Wiles CM, Wilmshurst P, Byrne C, Hesp R, Lowy C, Weissberger A (1991) Growth hormone therapy in adults with growth hormone deficiency. Acta Paediatr Scand 379:139–147

    CAS  Google Scholar 

  43. Tungtrongchitr R, Pongpaew P, Phonrat B, Tribunyatkul S, Viroonudomphol D, Supawan V, Jintaridhi P, Lertchavanakul A, Vudhivai N, Schelp FP (2001) Serum leptin and lipid profiles in Thai obese and overweight subjects. Int J Vit Nut Res 71:74–81

    Article  CAS  Google Scholar 

  44. D’Costa AP, Ingram RL, Lenham JE, Sonntag WE (1993) The regulation and mechanisms of action of growth hormone and insulin-like growth factor 1 during normal ageing. J Reprod Fertil Suppl 46:87–98

    PubMed  CAS  Google Scholar 

  45. Juul A, Bang P, Hertel NT (1994) Serum insulin-like growth factor-I in 1030 healthy children, adolescents, and adults: relation to age, sex, stage of puberty, testicular size, and body mass index. J Clin Endocrinol Metab 78:744–752

    Article  PubMed  CAS  Google Scholar 

  46. O’Connor KG, Tobin JD, Harman SM (1998) Serum levels of insulin-like growth factor-I are related to age and not to body composition in healthy women and men. J Gerontol A Biol Sci Med Sci 53:176–182

    Google Scholar 

  47. Seck T, Scheidt-Nave C, Ziegler R (1998) Positive association between circulating free thyroxine and insulin-like growth factor l concentrations in euthyroid elderly individuals. Clin Endocrinol 48:361–366

    Article  CAS  Google Scholar 

  48. Rutanen EM, Karkkainen T, Stenman UH, Yki-Jarvinen H (1993) Ageing is associated with decreased suppression of insulin-like growth factor binding protein-1 by insulin. J Clin Endocrinol Metab 77:1152–1155

    Article  PubMed  CAS  Google Scholar 

  49. Juul A (2003) Serum levels of insulin-like growth factor I and its binding proteins in health and disease. Growth Horm IGF Res 13:113–170

    Article  PubMed  CAS  Google Scholar 

  50. Kocyigit Y, Bayhan G, Atamer A, Atamer Y (2004) Serum levels of leptin, insulin-like growth factor-I and insulin-like growth factor binding protein-3 in women with pre-eclampsia, and their relationship to insulin resistance. Gynecol Endocrinol 18:341–348

    Article  PubMed  CAS  Google Scholar 

  51. Adeyemi E, Abdulle A (2000) A comparison of plasma leptin levels in obese and lean individuals in the United Arab Emirates. Nutr Res 20:157–166

    Article  CAS  Google Scholar 

  52. Ogier V, Ziegler O, Mejean L, Nicolas JP, Stricker-Krongrad A (2002) Obesity is associated with decreasing levels of the circulating soluble leptin receptor in humans. Int J Obes Relat Metab Disord 26:496–503

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

This study was supported by a grant from the Faculty of Medicine and Health Sciences (FMHS), United Arab Emirates University, Al-Ain, UAE.

Author information

Authors and Affiliations

  1. Department of Internal Medicine, Faculty of Medicine and Health Sciences, UAE University, 17666, Al Ain, UAE

    Abdishakur M. Abdulle & Enyioma N. Obineche

  2. Department of Biochemistry, Saba University, School of Medicine, Saba, Netherlands-Antilles

    Michael P. T. Gillett

  3. Department of Nephrology, Tawam Hospital, Al Ain, UAE

    Samra Abouchacra

  4. Department of Psychiatry, Faculty of Medicine, UAE University, Al-Ain, UAE

    Sufyan M. Sabri

  5. Department of Nephrology, Dubai Hospital, Dubai, UAE

    Mona Al Rukhaimi

  6. Department of Biological Sciences, Faculty of Science, University of Central Lancashire, PR1 2HE, Preston, UK

    Jaipaul Singh

Authors
  1. Abdishakur M. Abdulle
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Michael P. T. Gillett
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Samra Abouchacra
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sufyan M. Sabri
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mona Al Rukhaimi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Enyioma N. Obineche
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jaipaul Singh
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Abdishakur M. Abdulle.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Abdulle, A.M., Gillett, M.P.T., Abouchacra, S. et al. Low IGF-1 levels are associated with cardiovascular risk factors in haemodialysis patients. Mol Cell Biochem 302, 195–201 (2007). https://doi.org/10.1007/s11010-007-9441-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-007-9441-6

Keywords

Search

Navigation