IGF and Diabetes Complications

Review

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Rev Diabet Stud, 2020, 16:24-34 DOI 10.1900/RDS.2020.16.24

Insulin-like Growth Factor and its Therapeutic Potential for Diabetes Complications - Mechanisms and Metabolic Links: A Review

Belete Biadgo1, Workineh Tamir2, Sintayehu Ambachew1

1Department of Clinical Chemistry, School of Biomedical and Laboratory Sciences, College of Medicine and Health Sciences, University of Gondar, Ethiopia
2Department of Medical Laboratory Science, College of Medicine and Health Sciences, Debre Markos University, Debre Markos, Ethiopia
Address correspondence to: Belete Biadgo, e-mail: beletebiadigo@yahoo.com

Manuscript submitted August 16, 2020; resubmitted October 10, 2020; accepted October 31, 2020.

Keywords: insulin-like growth factor, diabetes complications, type 2 diabetes, insulin

Abstract

BACKGROUND: The insulin-like growth factor (IGF) system is an important system in normal physiological functioning of the body. In diabetes mellitus, alterations of IGF-binding protein (IGFBP) levels have been described, mainly in vascular complications. AIM: The aim of this review was to explore the role of the IGF system in reducing diabetes complications and its role as potential therapeutic target. RESULTS: IGF-1 plays a role in neuronal growth and developmental processes. Low concentrations of IGF-1 have been associated with neuropathy and other diabetes complications. Moreover, impaired IGF synthesis and function may result in cellular senescence and impaired vascular endothelial proliferation, adhesion, and integration. Of note, high IGF-1 bioavailability may prevent or delay the inception of diabetes-associated complications in diabetes patients. The mechanism of normal functioning IGF-1 is induced by increasing nitric oxide synthesis and potassium ion channel opening in cardiovascular physiology, which improves impaired small blood vessel function and reduces the occurrence of diabetes complications associated with reduced concentrations of IGF-1. CONCLUSIONS: IGF may be considered an alternative therapy for diabetes and diabetes-associated complications. Therefore, future studies should focus on the mechanism of action and therapeutic potential of IGFs in reducing the risk of development and progression of the disease in different clinical settings.

Abbreviations: ALS - acid-labile subunit; BRB - blood-retinal barrier; CVD - cardiovascular disease; DN - diabetic nephropathy; DNP - diabetic neuropathy; DR - diabetic retinopathy; ESRD - end-stage renal disease; fIGF - free insulin-like growth factor; GH - growth hormone; GHR - growth hormone receptor; IGF - insulin-like growth factor; IGF-1R/2R - insulin-like growth factor 1 receptor / 2 receptor; IGFBP - insulin-like growth factor binding protein; IR - insulin resistance; LDL - low-density lipoprotein; MetS - metabolic syndrome; T1D - type 1 diabetes mellitus; T2D - type 2 diabetes mellitus; VEGF - vascular endothelial growth factor

1. Introduction

The insulin-like growth factor (IGF) system is involved in the regulation of mammalian cell growth and differentiation, proliferation, and survival [1]. The system affects any of the other systems in our body. IGF-1 is a small protein consisting of 70 amino acids, with a molecular weight of 7.65 kilo Dalton, and the gene is located at chromosome 12q23 [1]. It is mainly produced by liver cells, but also by many other cells in our body [2].

The IGF system consists of:

  • 2 cell-surface receptors (IGF-1R and IGF-2R)
  • 2 ligands (IGF-1 and IGF-2)
  • 6 high-affinity IGF-binding proteins (IGFBP-1 to IGFBP-6) [3, 4]
  • Several associated IGFBP degrading protease enzymes.

The entire system is strongly controlled by a feedback loop involving growth hormones (GH) secreted by the pituitary, and GH production and secretion controlled by growth hormone-releasing hormone (GHRH) in the hypothalamus [4, 5] (Figure 1).

IGF-1 and IGFBP-3 are GH-dependent [6], while IGFBP-1 is insulin-regulated. IGFBP-1 production from the liver is significantly elevated during insulinopenia, and serum levels of bioactive IGF-1 are increased by insulin [7]. The production of IGFBP-3, -4, and -5 is stimulated by GH. IGFBP-3 is formed by the liver sinusoidal cells at the junction of the intravascular space. In circulation, IGF-1 is mainly bound to IGFBP-3, and this binary complex then binds to a large protein called the acid-labile subunit (ALS) to form a ternary complex [8, 9].

Insulin and IGF-1 are two related peptides with similar structure. They exercise their effects by interacting with their corresponding receptors, namely the insulin receptor and IGF-1R. The receptor-ligand interactions induce intracellular signaling cascades resulting in metabolic or mitogenic effects [10, 11] and are involved in regulation of metabolism. In contrast, IGF-1 overproduction in some pancreatic and non-pancreatic cancers has been linked to severe hypoglycemia [11].

Insulin encourages the constitutive secretion of IGF-1 from the liver. In turn, IGF-1 overruns insulin secretion even in normoglycemic situations [12]. Furthermore, a previous study showed that IGF-1 causes insulin activity and peripheral glucose utilizations to increase, hepatic glucose production to decrease, and lipid profiles in diabetes patients to improve [13].

IGFBP-1 is regulated mainly by insulin. It interacts with IGF-1 and IGF-2, and is used as a shuttle for IGFs to target tissues and regulate the action of free IGF-1. IGFPB-1 is regarded as the primary regulator of IGF-1 bioactivity and has an important part in the progression of diabetes and diabetes-related complications [14]. Lewitt et al. reported that the IGF system has an imperative pathophysiological role across a range of metabolic abnormalities, including obesity, insulin resistance (IR), and diabetes [15].

The exact mechanisms by which type 1 diabetes (T1D) and poor glycemic control relate to the GH-axis and its interaction with IGF-1 and IGFBP-3 remain to be determined. Nambam and Schatz have shown that GH insensitivity in combination with low concentrations of IGF-1 is frequently observed in T1D patients [16]. However, controversies have been described in diabetes complications such as diabetic retinopathy (DR) [17]. According to Bazzaz et al., growth factors are associated with the development of DR, diabetic nephropathy (DN), and diabetic neuropathy (DNP). However, this article showed that growth factors, including vascular endothelial growth factor (VEGF), IGF-1, and tumor necrosis growth factor, may have a protective role in the progression and development of diabetes complications [18].

The pathogenesis of DR is a complex process involving ischemia and hyperglycemia; growth factors may result in neovascularization and loss of vision. There is controversy about the serum IGF-1 level that correlates with the progression of retinal neovascularization in clinical diabetes and increased or decreased concentrations of IGF-1 in the vitreous or serum levels of patients with DR [19]. Neamtu et al. showed that decreased concentrations of IGF-1 were positively correlated with diabetes and diabetes-related complications [20].

Evidence has suggested that patients with T1D may have aberrations of the GH/IGF/IGFBP axis, including GH hypersecretion, decreased concentrations of circulating IGF-1 and IGFBP-3, and elevated levels of IGFBP-1 [12]. These abnormalities may exacerbate hyperglycemia in patients with T1D and play a role in the pathogenesis of diabetes-related complications [21]. Also, IGF-1 deficit has been reported to be significantly associated with the risk of developing impaired glucose tolerance, IR, and type 2 diabetes mellitus (T2D) [22]. The study also suggested that IGF-1 deficit may be a factor in the pathogenesis of schizophrenia [22]. Knott in 1998 presented a clear association between high levels of IGF-1 and the progression of DR [23]. Therefore, the aim of this review was to discuss a large body of evidence on the therapeutic potential of human IGF-1 in diabetes complications and to understand the mechanism and metabolic links of IGF in diabetes complications.

2. The physiology of the IGF system

Acknowledgments: BB, WT, and SA each contributed to literature search, writing, and editing of this article.

References

  1. Brissenden JE, Ullrich A, Francke U. Human chromosomal mapping of genes for insulin-like growth factors I and II and epidermal growth factor. Nature 1984. 310(5980):781-784. [DOD] [CrossRef]
  2. Le Roith D, Scavo L, Butler A. What is the role of circulating IGF-I? Trends Endocrinol Metab 2001. 12(2):48-52. [DOD] [CrossRef]
  3. Hwa V, Oh Y, Rosenfeld RG. The insulin-like growth factor-binding protein (IGFBP) superfamily. Endocr Rev 1999. 20(6):761-787. [DOD] 
  4. Romero CJ, Pine-Twaddell E, Sima DI, Miller RS, He L, Wondisford F, et al. Insulin-like growth factor 1 mediates negative feedback to somatotroph GH expression via POU1F1/CREB binding protein interactions. Mol Cell Biol 2012. 32(21):4258-4269. [DOD] [CrossRef]
  5. Roelfsema V, Clark RG. The growth hormone and insulin-like growth factor axis: its manipulation for the benefit of growth disorders in renal failure. J Am Soc Nephrol 2001. 12(6):1297-1306. [DOD] 
  6. Wang Y, Zhang H, Cao M, Kong L, Ge X. Analysis of the value and correlation of IGF-1 with GH and IGFBP-3 in the diagnosis of dwarfism. Exp Ther Med 2019. 17(5):3689-3693. [DOD] 
  7. Bae JH, Song DK, Im SS. Regulation of IGFBP-1 in metabolic diseases. J Lifestyle Med 2013. 3(2):73. [DOD] 
  8. David A, Hwa V, Metherell LA, Netchine I, Camacho-Hübner C, Clark AJ, Rosenfeld RG, Savage MO. Evidence for a continuum of genetic, phenotypic, and biochemical abnormalities in children with growth hormone insensitivity. Endocr Rev 2011. 32(4):472-497. [DOD] [CrossRef]
  9. Blum WF, Alherbish A, Alsagheir A, El Awwa A, Kaplan W, Koledova E, Savage MO. The growth hormone-insulin-like growth factor-I axis in the diagnosis and treatment of growth disorders. Endocr Connect 2018. 7(6):R212-R222. [DOD] [CrossRef]
  10. Bäck K. Interaction between insulin and IGF-I receptors in insulin sensitive and insulin resistant cells and tissues. Linköping University Electronic Press, 2011. [DOD] 
  11. Lu S, Purohit S, Sharma A, Zhi W, He M, Wang Y, Li C, She J. Serum insulin-like growth factor binding protein 6 (IGFBP6) is increased in patients with type 1 diabetes and its complications. Int J Clin Exp Med 2012. 5(3):229. [DOD] 
  12. Palakawong P, Arakaki R. Diabetic ketoacidosis in acromegaly: A case report. Endocr Pract 2012. 27:1-15. [DOD] [CrossRef]
  13. Janssen JA, Lamberts SW. The role of IGF-I in the development of cardiovascular disease in type 2 diabetes mellitus: is prevention possible? Eur J Endocrinol 2002. 146(4):467-477. [DOD] 
  14. Gu T, Falhammar H, Gu HF, Brismar K. Epigenetic analyses of the insulin-like growth factor binding protein 1 gene in type 1 diabetes and diabetic nephropathy. Clin Epigenetics 2014. 6(1):10. [DOD] [CrossRef]
  15. Lewitt M, Dent M, Hall K. The insulin-like growth factor system in obesity, insulin resistance and type 2 diabetes mellitus. J Clin Med 2014. 3(4):1561-1574. [DOD] [CrossRef]
  16. Nambam B, Schatz D. Growth hormone and insulin-like growth factor-I axis in type 1 diabetes. Growth Horm IGF Res 2018. 38:49-52. [DOD] [CrossRef]
  17. Khan ZA, Chakrabarti S. Growth factors in proliferative diabetic retinopathy. Exp Diabesity Res 2003. 4(4):287-301. [DOD] [CrossRef]
  18. Bazzaz JT, Amoli MM, Taheri Z, Larijani B, Pravica V, Hutchinson IV. TGF-beta1 and IGF-I gene variations in type 1 diabetes microangiopathic complications. J Diabetes Metab Disord 2014. 13(1):45. [DOD] [CrossRef]
  19. Kummer A, Pulford BE, Ishii DN, Seigel GM. Des (1-3) IGF-1 treatment normalizes type 1 IGF receptor and phospho-Akt (Thr 308) immunoreactivity in predegenerative retina of diabetic rats. Int J Exp Diabesity Res 2003. 4(1):45-57. [DOD] [CrossRef]
  20. Neamtu MC, Avramescu ET, Marcu IR, Turcu-stiolica A, Boldeanu MV, Neamtu OM, Tudorache S, Miulescu RE. The correlation between insulin-like growth factor with glycemic control, glomerular filtration rate, blood pressure, hematological changes or body mass index in patients with type 2 diabetes mellitus. Rom J Morphol Embryol 2017. 58:857-861. [DOD] 
  21. Thrailkill KM. Insulin-like growth factor-I in diabetes mellitus: its physiology, metabolic effects, and potential clinical utility. Diabetes Technol Ther 2000. 2(1):69-80. [DOD] [CrossRef]
  22. Venkatasubramanian G, Chittiprol S, Neelakantachar N, Naveen MN, Thirthall J, Gangadhar BN, Shetty KT. Insulin and insulin-like growth factor-1 abnormalities in antipsychotic-naive schizophrenia. Am J Psychiatry 2007. 164(10):1557-1560. [DOD] [CrossRef]
  23. Knott RM. Insulin-like growth factor type 1 - friend or foe? BMJ Publishing Group Ltd, 1998. [DOD] 
  24. Roith DL. The insulin-like growth factor system. Exp Diabesity Res 2003. 4(4):205-212. [DOD] [CrossRef]
  25. Retnakaran R. The insulin-like growth factor axis: a new player in gestational diabetes mellitus? Diabetes 2016. 65(11):3246-3248. [DOD] 
  26. Adamek A, Kasprzak A. Insulin-like growth factor (IGF) system in liver diseases. Int J Mol Sci 2018. 19(5):1308. [DOD] [CrossRef]
  27. Arcaro A. Targeting the insulin-like growth factor-1 receptor in human cancer. Front Pharmacol 2013. 4:30. [DOD] [CrossRef]
  28. Sima AA, Li ZG, Zhang W. The insulin-like growth factor system and neurological complications in diabetes. Exp Diabesity Res 2003. 4(4):235-256. [DOD] [CrossRef]
  29. Skalkidou A, Petridou E, Papathoma E, Salvanos H, Kedikoglou S, Chrousos G, Trichopoulos D. Determinants and consequences of major insulin-like growth factor components among full-term healthy neonates. Cancer Epidemiol Biomarkers Prev 2003. 12(9):860-865. [DOD] 
  30. Bajpai A, Menon P. Insulin like growth factors axis and growth disorders. Indian J Pediatr 2006. 73(1):67-71. [DOD] [CrossRef]
  31. Laron Z. Insulin-like growth factor 1 (IGF-1): a growth hormone. Mol Pathol 2001. 54(5):311. [DOD] [CrossRef]
  32. Ishii DN, Lupien SB. Insulin-like growth factor replacement therapy for diabetic neuropathy: Experimental basis. Exp Diabesity Res 2003. 4(4):257-269. [DOD] [CrossRef]
  33. Kim HS, Rosenfeld RG, Oh Y. Biological roles of insulin-like growth factor binding proteins (IGFBPs). Exp Mol Med 1997. 29(2):85. [DOD] [CrossRef]
  34. Rajpathak SN, He M, Sun Q, Kaplan RC, Muzumdar R, Rohan TE, Gunter MJ, Pollak M, Kim M, Pessin JE, et al. Insulin-like growth factor axis and risk of type 2 diabetes in women. Diabetes 2012. 61(9):2248-2254. [DOD] [CrossRef]
  35. Bachner-Melman R, Zohar AH, Nemanov L, Heresco-Levy U, Gritsenko I, Ebstein RP. Association between the insulin-like growth factor 2 gene (IGF2) and scores on the eating attitudes test in nonclinical subjects: a family-based study. Am J Psychiatry 2005. 162(12):2256-2262. [DOD] [CrossRef]
  36. Boucher J, Kleinridders A, Kahn CR. Insulin receptor signaling in normal and insulin-resistant states. Cold Spring Harb Perspect Biol 2014. 6(1):a009191. [DOD] [CrossRef]
  37. Leung KC, Johannsson G, Leong GM, Ho KK. Estrogen regulation of growth hormone action. Endocr Rev 2004. 25:693-721. [DOD] [CrossRef]
  38. Berryman DE, Glad CA, List EO, Johannsson G. The GH/IGF-1 axis in obesity: Pathophysiology and therapeutic considerations. Nat Rev Endocrinol 2013. 9:346-356. [DOD] [CrossRef]
  39. Dynkevich YR, Rother KI, Whitford I, Qureshi S, Galiveeti S, Szulc AL, Danoff A, Breen TL, Kaviani N, Shanik MH, et al. Tumors, IGF-2, and hypoglycemia: Insights from the clinic, the laboratory, and the historical archive. Endocr Rev 2013. 34:798-826. [DOD] [CrossRef]
  40. Kostecka Z, Blahovec J. Animal insulin-like growth factor binding proteins and their biological functions. Vet Med (Praha) 2002. 47(2/3):75-84. [DOD] 
  41. Ahmed RL, Thomas W, Schmitz KH. Interactions between insulin, body fat, and insulin-like growth factor axis proteins. Cancer Epidemiol Biomarkers Prev 2007. 16(3):593-597. [DOD] [CrossRef]
  42. Clemmons DR. Metabolic actions of insulin-like growth factor-I in normal physiology and diabetes. Endocrinol Metab Clin North Am 2012. 41:425-443. [DOD] [CrossRef]
  43. Gutefeldt K, Hedman CA, Thyberg IS, Bachrach-Lindström M, Spangeus A, Arnqvist HJ. Dysregulated growth hormone insulin-like growth factor-1 axis in adult type 1 diabetes with long duration. Clin Endocrinol 2018. 89:424-430. [DOD] [CrossRef]
  44. Fu Z, R Gilbert E, Liu D. Regulation of insulin synthesis and secretion and pancreatic Beta-cell dysfunction in diabetes. Curr Diabetes Rev 2013. 9(1):25-53. [DOD] [CrossRef]
  45. Fernandez AM, Kim JK, Yakar S, Dupont J, Hernandez-Sanchez C, Castle AL, Filmore J, Shulman GI, Roith DL. Functional inactivation of the IGF-I and insulin receptors in skeletal muscle causes type 2 diabetes. Genes Dev 2001. 15(15):1926-1934. [DOD] [CrossRef]
  46. Djiogue S, Kamdje AH, Vecchio L, Kipanyula MJ, Farahna M, Aldebasi Y, Etet PF. Insulin resistance and cancer: the role of insulin and IGFs. Endocr Relat Cancer 2013. 20(1):R1-R17. [DOD] [CrossRef]
  47. Yakar S, Liu JL, Fernandez AM, Wu Y, Schally AV, Frystyk J, Chernausek SD, Mejia W, Roith DL. Liver-specific igf-1 gene deletion leads to muscle insulin insensitivity. Diabetes. 2001. 50(5):1110-1118. [DOD] 
  48. Yakar S, Kim H, Zhao H, Toyoshima Y, Pennisi P, Gavrilova O, Leroith D. The growth hormone-insulin like growth factor axis revisited: lessons from IGF-1 and IGF-1 receptor gene targeting. Pediatr Nephrol 2005. 20(3):251-254. [DOD] [CrossRef]
  49. Friedrich N, Thuesen B, Jørgensen T, Juul A, Spielhagen C, Wallaschofksi H, Linneberg A. The association between IGF-I and insulin resistance: a general population study in Danish adults. Diabetes Care 2012. 35(4):768-773. [DOD] [CrossRef]
  50. McDonald A, Williams RM, Regan FM, Semple RK, Dunger DB. IGF-I treatment of insulin resistance. Eur J Endocrinol 2007. 157(Suppl 1):S51-S56. [DOD] [CrossRef]
  51. Clemmons DR. The relative roles of growth hormone and IGF-1 in controlling insulin sensitivity. J Clin Invest 2004. 113(1):25-27. [DOD] [CrossRef]
  52. Loh K, Zhang L, Brandon A, Wang Q, Begg D, Qi Y, Fu M, Kulkarni R, Teo J, Baldock P, et al. Insulin controls food intake and energy balance via NPY neurons. Mol Metab 2017. 6(6):574-584. [DOD] [CrossRef]
  53. Dahlkvist HH. Insulin and IGF-1 as Critical Metabolic Regulators. Endocrinol Metab Syndr 2015. 4:1. [DOD] [CrossRef]
  54. Heald AH, Kärvestedt L, Anderson SG, McLaughlin J, Knowles A, Wong L, Grill V, Cruickshank JK, White A, Gibson JM, Brismar K. Low insulin-like growth factor-II levels predict weight gain in normal weight subjects with type 2 diabetes. Am J Med 2006. 119(2):167. [DOD] 
  55. Barzilai N, Huffman DM, Muzumdar RH, Bartke A. The critical role of metabolic pathways in aging. Diabetes 2012. 61(6):1315-1322. [DOD] [CrossRef]
  56. Kreitschmann-Andermahr I, Suarez P, Jennings R, Evers N, Brabant G. GH/IGF-I regulation in obesity–mechanisms and practical consequences in children and adults. Horm Res Paediatr 2010. 73(3):153-160. [DOD] [CrossRef]
  57. Le Roith D. Seminars in medicine of the Beth Israel Deaconess Medical Center. insulin-like growth factors. N Engl J Med 1997. 336: 633-640. [DOD] [CrossRef]
  58. Sesti G, Sciacqua A, Cardellini M, Marini MA, Maio R, Vatrano M, Succurro E, Lauro R, Federici M, Perticone F. Plasma concentration of IGF-I is independently associated with insulin sensitivity in subjects with different degrees of glucose tolerance. Diabetes Care 2005. 28(1):120-125. [DOD] [CrossRef]
  59. Sharma A, Purohit S, Sharma S, Bai S, Zhi W, Ponny SR, Hopkins D, Steed L, Bode B, Anderson SW, She JX. IGF-binding proteins in type-1 diabetes are more severely altered in the presence of complications. Front Endocrinol 2016. 7:2. [DOD] [CrossRef]
  60. Kielczewski JL, Calzi SL, Shaw LC, Cai J, Qi X, Ruan Q, Wu L, Liu L, Hu P, Chan-Ling T, et al. Free insulin-like growth factor binding protein-3 (IGFBP-3) reduces retinal vascular permeability in association with a reduction of acid sphingomyelinase (ASMase). Invest Ophthalmol Vis Sci 2011. 52(11):8278-8286. [DOD] [CrossRef]
  61. Zhang J, Zhang L, Quan L, Qi W, Jiang Y, Jiang S. Correlation of retinopathy with serum levels of growth hormones and insulin-like growth factor-1 in patients with diabetic retinopathy. Int J Clin Exp Med 2017. 10(1):1325-1329. [DOD] 
  62. Wang H, Xu J, Chen J, Little PJ, Zheng W. Role of IGF-1 signaling in the pathology of diabetic retinopathy. Ther Targets Neurol Dis 2015. 2:e639. [DOD] 
  63. Tepper OM, Galiano RD, Capla JM, Kalka C, Gagne PJ, Jacobowitz GR, Levine JP, Gurtner GC. Human endothelial progenitor cells from type II diabetics exhibit impaired proliferation, adhesion, and incorporation into vascular structures. Circulation 2002. 106(22):2781-2786. [DOD] [CrossRef]
  64. Bach LA. Endothelial cells and the IGF system. J Mol Endocrinol 2014. 54(1):R1-R13. [DOD] [CrossRef]
  65. Frystyk J, Ledet T, Moller N, Flyvbjerg A, Orskov H. Cardiovascular disease and insulin-like growth factor 1. Circulation 2002. 106 (8):893-895. [DOD] [CrossRef]
  66. Conti E, Musumeci MB, De Giusti M, Dito E, Mastromarino V, Autore C, Volpe M. IGF-1 and atherothrombosis: relevance to pathophysiology and therapy. Clin Sci (Lond) 2011. 120(9):377-402. [DOD] [CrossRef]
  67. Piccioli L, Arcopinto M, Salzano A, D’Assante R, Schiavo A, Stagnaro FM, Lombardi A, Panicara V, Valente P, Vitale G, et al. The impairment of the growth hormone/insulin-like growth factor 1 (IGF-1) axis in heart failure: A possible target for future therapy. Monaldi Arch Chest Dis 2018. 88(3):975. [DOD] [CrossRef]
  68. Wallander M, Norhammar A, Malmberg K, Öhrvik J, Ryden L, Brismar K. Insulin-like growth factor binding protein 1 predicts cardiovascular morbidity and mortality in patients with acute myocardial infarction and type 2 diabetes. Diabetes Care 2007. 30(9):2343-2348. [DOD] [CrossRef]
  69. Komamura K, Miyatake K, Hanatani A, Hashimura K, Kimu C, Ueda H. Insulin-like growth factor-1 improves cardiac function and symptoms in the patients on the waiting list for transplantation with dilated cardiomyopathy. Clinical and Basic Research in Heart Failure (M). The 69th Annual Scientific Meeting of the Japanese Circulation Society. Circulation 2005. 69:130. [DOD] 
  70. Barton J, Hindmarsh P, Preece M. Serum insulin-like growth factor 1 in congenital heart disease. Arch Dis Child 1996. 75(2):162-163. [DOD] [CrossRef]
  71. Watkins P, Thomas P. Diabetes mellitus and the nervous system. J Neurol Neurosurg Psychiatry 1998. 65(5):620-632. [DOD] [CrossRef]
  72. Maji D, Singh A. Clinical trial of D-400, a herbomineral preparation in diabetes mellitus. J Diabetic Assoc India 1995. 35(1):1-4. [DOD] 
  73. Zhuang HX, Wuarin L, Fei ZJ, Ishii DN. Insulin-like growth factor (IGF) gene expression is reduced in neural tissues and liver from rats with non-insulin-dependent diabetes mellitus, and IGF treatment ameliorates diabetic neuropathy. J Pharmacol Exp Ther 1997. 283(1):366-374. [DOD] 
  74. Friedrich N, Thuesen B, Jorgensen T, Juul A, Spielhagen C, Wallaschofksi H, Linneberg A. The association between IGF-I and insulin resistance: a general population study in Danish adults. Diabetes Care 2012. 35(4):768-773. [DOD] [CrossRef]
  75. Malone JI. Diabetic central neuropathy: CNS damage related to hyperglycemia. Diabetes 2016. 65(2):355-357. [DOD] [CrossRef]
  76. American Diabetes Association. Standards of medical care in diabetes-2015 abridged for primary care providers. Clin Diabetes 2015. 33(2):97. [DOD] [CrossRef]
  77. Pugliese G. Updating the natural history of diabetic nephropathy. Acta Diabetol 2014. 51(6):905-915. [DOD] [CrossRef]
  78. Persson F, Rossing P. Diagnosis of diabetic kidney disease: state of the art and future perspective. Kidney Int Suppl 2018. 8(1):2-7. [DOD] [CrossRef]
  79. Nazar CM. Diabetic nephropathy; principles of diagnosis and treatment of diabetic kidney disease. J Nephropharmacol 2014. 3(1):15. [DOD] 
  80. Kamenicky P, Mazziotti G, Lombes M, Giustina A, Chanson P. Growth hormone, insulin-like growth factor-1, and the kidney: pathophysiological and clinical implications. Endocr Rev 2014. 35(2):234-281. [DOD] [CrossRef]
  81. Carroll PV, Christ ER, Umpleby AM, Gowrie I, Jackson N, Bowes SB, Hovorka R, Croos P, Sönksen PH, Russell-Jones DL. IGF-I treatment in adults with type 1 diabetes: effects on glucose and protein metabolism in the fasting state and during a hyperinsulinemic-euglycemic amino acid clamp. Diabetes 2000. 49(5):789-796. [DOD] [CrossRef]

 
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