Insulin-like growth factor 1#Aging

Insulin-like growth factor 1 (IGF-1), also called somatomedin C, is a hormone similar in molecular structure to insulin which plays an important role in childhood growth, and has anabolic effects in adults.{{cite journal | vauthors = Tahimic CG, Wang Y, Bikle DD | title = Anabolic effects of IGF-1 signaling on the skeleton | journal = Frontiers in Endocrinology | volume = 4 | pages = 6 | date = 2013 | pmid = 23382729 | pmc = 3563099 | doi = 10.3389/fendo.2013.00006 | doi-access = free }} In the 1950s IGF-1 was called "sulfation factor" because it stimulated sulfation of cartilage in vitro,{{cite journal | vauthors = Salmon WD, Daughaday WH | title = A hormonally controlled serum factor which stimulates sulfate incorporation by cartilage in vitro | journal = The Journal of Laboratory and Clinical Medicine | volume = 49 | issue = 6 | pages = 825–836 | date = June 1957 | pmid = 13429201 }} and in the 1970s due to its effects it was termed "nonsuppressible insulin-like activity" (NSILA).{{cite journal | vauthors = Meuli C, Zapf J, Froesch ER | title = NSILA-carrier protein abolishes the action of nonsuppressible insulin-like activity (NSILA-S) on perfused rat heart | journal = Diabetologia | volume = 14 | issue = 4 | pages = 255–259 | date = April 1978 | pmid = 640301 | doi = 10.1007/BF01219425 }}

IGF-1 is a protein that in humans is encoded by the IGF1 gene.{{cite journal | vauthors = Höppener JW, de Pagter-Holthuizen P, Geurts van Kessel AH, Jansen M, Kittur SD, Antonarakis SE, Lips CJ, Sussenbach JS | title = The human gene encoding insulin-like growth factor I is located on chromosome 12 | journal = Human Genetics | volume = 69 | issue = 2 | pages = 157–160 | year = 1985 | pmid = 2982726 | doi = 10.1007/BF00293288 | s2cid = 5825276 }}{{cite journal | vauthors = Jansen M, van Schaik FM, Ricker AT, Bullock B, Woods DE, Gabbay KH, Nussbaum AL, Sussenbach JS, Van den Brande JL | title = Sequence of cDNA encoding human insulin-like growth factor I precursor | journal = Nature | volume = 306 | issue = 5943 | pages = 609–611 | year = 1983 | pmid = 6358902 | doi = 10.1038/306609a0 | s2cid = 4336584 | bibcode = 1983Natur.306..609J }} IGF-1 consists of 70 amino acids in a single chain with three intramolecular disulfide bridges. IGF-1 has a molecular weight of 7,649 daltons.{{cite journal | vauthors = Rinderknecht E, Humbel RE | title = The amino acid sequence of human insulin-like growth factor I and its structural homology with proinsulin | journal = The Journal of Biological Chemistry | volume = 253 | issue = 8 | pages = 2769–2776 | date = April 1978 | pmid = 632300 | doi = 10.1016/S0021-9258(17)40889-1 | doi-access = free }} In dogs, an ancient mutation in IGF1 is the primary cause of the toy phenotype.{{cite journal | vauthors = Callaway E | title = Big dog, little dog: mutation explains range of canine sizes | journal = Nature | volume = 602 | issue = 7895 | pages = 18 | date = February 2022 | pmid = 35087254 | doi = 10.1038/d41586-022-00209-0 | s2cid = 246359754 | bibcode = 2022Natur.602...18C }}

IGF-1 is produced primarily by the liver. Production is stimulated by growth hormone (GH). Most of IGF-1 is bound to one of 6 binding proteins (IGF-BP). IGFBP-1 is regulated by insulin. IGF-1 is produced throughout life; the highest rates of IGF-1 production occur during the pubertal growth spurt.{{cite journal | vauthors = Decourtye L, Mire E, Clemessy M, Heurtier V, Ledent T, Robinson IC, Mollard P, Epelbaum J, Meaney MJ, Garel S, Le Bouc Y, Kappeler L | title = IGF-1 Induces GHRH Neuronal Axon Elongation during Early Postnatal Life in Mice | journal = PLOS ONE | volume = 12 | issue = 1 | pages = e0170083 | date = 2017 | pmid = 28076448 | pmc = 5226784 | doi = 10.1371/journal.pone.0170083 | doi-access = free | bibcode = 2017PLoSO..1270083D }} The lowest levels occur in infancy and old age.{{cite journal | vauthors = Suwa S, Katsumata N, Maesaka H, Tokuhiro E, Yokoya S | title = Serum insulin-like growth factor I (somatomedin-C) level in normal subjects from infancy to adulthood, pituitary dwarfs and normal variant short children | journal = Endocrinologia Japonica | volume = 35 | issue = 6 | pages = 857–864 | date = December 1988 | pmid = 3250861 | doi = 10.1507/endocrj1954.35.857 | s2cid = 6965802 | doi-access = free }}{{cite journal | vauthors = Landin-Wilhelmsen K, Wilhelmsen L, Lappas G, Rosén T, Lindstedt G, Lundberg PA, Bengtsson BA | title = 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 | journal = Clinical Endocrinology | volume = 41 | issue = 3 | pages = 351–357 | date = September 1994 | pmid = 7955442 | doi = 10.1111/j.1365-2265.1994.tb02556.x | s2cid = 24346368 }}

Low IGF-1 levels are associated with cardiovascular disease, while high IGF-1 levels are associated with cancer. Mid-range IGF-1 levels are associated with the lowest mortality.

A synthetic analog of IGF-1, mecasermin, is used for the treatment of growth failure in children with severe IGF-1 deficiency.{{cite journal | vauthors = Keating GM | title = Mecasermin | journal = BioDrugs | volume = 22 | issue = 3 | pages = 177–188 | year = 2008 | pmid = 18481900 | doi = 10.2165/00063030-200822030-00004 }} Cyclic glycine-proline (cGP) is a metabolite of hormone insulin-like growth factor-1 (IGF-1). It has a cyclic structure, lipophilic nature, and is enzymatically stable which makes it a more favourable candidate for manipulating the binding-release process between IGF-1 and its binding protein, thereby normalising IGF-1 function.{{cite journal | vauthors = Guan J, Li F, Kang D, Anderson T, Pitcher T, Dalrymple-Alford J, Shorten P, Singh-Mallah G | title = Cyclic Glycine-Proline (cGP) Normalises Insulin-Like Growth Factor-1 (IGF-1) Function: Clinical Significance in the Ageing Brain and in Age-Related Neurological Conditions | journal = Molecules | volume = 28 | issue = 3 | pages = 1021 | date = January 2023 | pmid = 36770687 | pmc = 9919809 | doi = 10.3390/molecules28031021 | doi-access = free }}

Synthesis and circulation

{{see also|Neurobiological effects of physical exercise#IGF-1 signaling}}

The polypeptide hormone IGF-1 is synthesized primarily in the liver upon stimulation by growth hormone (GH). It is a key mediator of anabolic activities in numerous tissues and cells, such as growth hormone-stimulated growth, metabolism and protein translation.{{cite journal | vauthors = Larsson SC, Michaëlsson K, Burgess S | title = IGF-1 and cardiometabolic diseases: a Mendelian randomisation study | journal = Diabetologia | volume = 63 | issue = 9 | pages = 1775–1782 | date = September 2020 | pmid = 32548700 | pmc = 7406523 | doi = 10.1007/s00125-020-05190-9 }} Due to its participation in the GH-IGF-1 axis it contributes among other things to the maintenance of muscle strength, muscle mass, development of the skeleton and is a key factor in brain, eye and lung development during fetal development.{{Cite journal | vauthors = Guo J, Xie J, Zhou B, Găman MA, Kord-Varkaneh H, Clark CC, Salehi-Sahlabadi A, Li Y, Han X, Hao Y, Liang Y |date=2020-04-01 |title=The influence of zinc supplementation on IGF-1 levels in humans: A systematic review and meta-analysis |journal=Journal of King Saud University - Science |volume=32 |issue=3 |pages=1824–1830 |doi=10.1016/j.jksus.2020.01.018 |issn=1018-3647}}

Studies have shown the importance of the GH/IGF-1 axis in directing development and growth, where mice with a IGF-1 deficiency had a reduced body- and tissue mass. Mice with an excessive expression of IGF-1 had an increased mass.{{cite journal | vauthors = Xie W, Tang Z, Guo Y, Zhang C, Zhang H, Han Y, Yuan Z, Weng Q | title = Seasonal expressions of growth hormone receptor, insulin-like growth factor 1 and insulin-like growth factor 1 receptor in the scented glands of the muskrats (Ondatra zibethicus) | journal = General and Comparative Endocrinology | volume = 281 | pages = 58–66 | date = September 2019 | pmid = 31121166 | doi = 10.1016/j.ygcen.2019.05.014 | s2cid = 163168020 }}

The levels of IGF-1 in the body vary throughout life, depending on age, where peaks of the hormone is generally observed during puberty and the postnatal period. After puberty, when entering the third decade of life, there is a rapid decrease in IGF-1 levels due to the actions of GH. Between the third and eighth decade of life, the IGF-1 levels decrease gradually, but unrelated to functional decline. However, protein intake is proven to increase IGF-1 levels.{{cite journal | vauthors = Levine ME, Suarez JA, Brandhorst S, Balasubramanian P, Cheng CW, Madia F, Fontana L, Mirisola MG, Guevara-Aguirre J, Wan J, Passarino G, Kennedy BK, Wei M, Cohen P, Crimmins EM, Longo VD | title = Low protein intake is associated with a major reduction in IGF-1, cancer, and overall mortality in the 65 and younger but not older population | journal = Cell Metabolism | volume = 19 | issue = 3 | pages = 407–417 | date = March 2014 | pmid = 24606898 | pmc = 3988204 | doi = 10.1016/j.cmet.2014.02.006 }}Image:IGF-1.GIF

Mechanism of action

IGF-1 is a primary mediator of the effects of growth hormone (GH). Growth hormone is made in the anterior pituitary gland, released into the bloodstream, and then stimulates the liver to produce IGF-1. IGF-1 then stimulates systemic body growth, and has growth-promoting effects on almost every cell in the body, especially skeletal muscle, cartilage, bone, liver, kidney, nerve, skin, hematopoietic, and lung cells. In addition to its insulin-like effects (insulin being the main anabolic hormone in the body),{{cite book | vauthors = Voet D, Voet JG | title = Biochemistry | date = 2011 | publisher = Wiley | location = New York | edition = 4th }} IGF-1 can also regulate cellular DNA synthesis.{{cite journal | vauthors = Yakar S, Rosen CJ, Beamer WG, Ackert-Bicknell CL, Wu Y, Liu JL, Ooi GT, Setser J, Frystyk J, Boisclair YR, LeRoith D | title = Circulating levels of IGF-1 directly regulate bone growth and density | journal = The Journal of Clinical Investigation | volume = 110 | issue = 6 | pages = 771–781 | date = September 2002 | pmid = 12235108 | pmc = 151128 | doi = 10.1172/JCI15463 }}

IGF-1 binds to at least two cell surface receptor tyrosine kinases: the IGF-1 receptor (IGF1R), and the insulin receptor. Its primary action is mediated by binding to its specific receptor, IGF1R, which is present on the surface of several cell types in a multitude of tissues. Binding to the IGF1R initiates intracellular signaling. IGF-1 is one of the most potent natural activators of the Akt signaling pathway, a stimulator of cell growth and proliferation, and a potent inhibitor of programmed cell death.{{cite journal | vauthors = Peruzzi F, Prisco M, Dews M, Salomoni P, Grassilli E, Romano G, Calabretta B, Baserga R | title = Multiple signaling pathways of the insulin-like growth factor 1 receptor in protection from apoptosis | journal = Molecular and Cellular Biology | volume = 19 | issue = 10 | pages = 7203–7215 | date = October 1999 | pmid = 10490655 | pmc = 84713 | doi = 10.1128/mcb.19.10.7203 }}{{cite journal | vauthors = Juin P, Hueber AO, Littlewood T, Evan G | title = c-Myc-induced sensitization to apoptosis is mediated through cytochrome c release | journal = Genes & Development | volume = 13 | issue = 11 | pages = 1367–1381 | date = June 1999 | pmid = 10364155 | pmc = 316765 | doi = 10.1101/gad.13.11.1367 }} The IGF-1 receptor and insulin receptor are two closely related members of a transmembrane tetrameric tyrosine kinase receptor family. They control vital brain functions, such as survival, growth, energy metabolism, longevity, neuroprotection and neuroregeneration.{{cite journal | vauthors = Moloney AM, Griffin RJ, Timmons S, O'Connor R, Ravid R, O'Neill C | title = Defects in IGF-1 receptor, insulin receptor and IRS-1/2 in Alzheimer's disease indicate possible resistance to IGF-1 and insulin signalling | journal = Neurobiology of Aging | volume = 31 | issue = 2 | pages = 224–243 | date = February 2010 | pmid = 18479783 | doi = 10.1016/j.neurobiolaging.2008.04.002 | s2cid = 14265087 }}

= Metabolic effects =

As a major growth factor, IGF-1 is responsible for stimulating growth of all cell types, and causing significant metabolic effects.{{cite journal | vauthors = Clemmons DR | title = Metabolic actions of insulin-like growth factor-I in normal physiology and diabetes | journal = Endocrinology and Metabolism Clinics of North America | volume = 41 | issue = 2 | pages = 425–43, vii-viii | date = June 2012 | pmid = 22682639 | pmc = 3374394 | doi = 10.1016/j.ecl.2012.04.017 }} One important metabolic effect of IGF-1 is signaling cells that sufficient nutrients are available for them to undergo hypertrophy and cell division.{{cite journal | vauthors = Bikle DD, Tahimic C, Chang W, Wang Y, Philippou A, Barton ER | title = Role of IGF-I signaling in muscle bone interactions | journal = Bone | volume = 80 | pages = 79–88 | date = November 2015 | pmid = 26453498 | pmc = 4600536 | doi = 10.1016/j.bone.2015.04.036 }} Its effects also include inhibiting cell apoptosis and increasing the production of cellular proteins. IGF-1 receptors are ubiquitous, which allows for metabolic changes caused by IGF-1 to occur in all cell types. IGF-1's metabolic effects are far-reaching and can coordinate protein, carbohydrate, and fat metabolism in a variety of different cell types. The regulation of IGF-1's metabolic effects on target tissues is also coordinated with other hormones such as growth hormone and insulin.{{cite journal | vauthors = Clemmons DR | title = The relative roles of growth hormone and IGF-1 in controlling insulin sensitivity | journal = The Journal of Clinical Investigation | volume = 113 | issue = 1 | pages = 25–27 | date = January 2004 | pmid = 14702105 | pmc = 300772 | doi = 10.1172/JCI200420660 }}

= The IGF system =

IGF-1 is part of the insulin-like growth factor (IGF) system. This system consists of three ligands (insulin, IGF-1 and IGF-2), two tyrosine kinase receptors (insulin receptor and IGF-1R receptor) and six ligand binding proteins (IGFBP 1–6).{{cite journal | vauthors = García-Mato Á, Cervantes B, Murillo-Cuesta S, Rodríguez-de la Rosa L, Varela-Nieto I | title = Insulin-like Growth Factor 1 Signaling in Mammalian Hearing | journal = Genes | volume = 12 | issue = 10 | pages = 1553 | date = September 2021 | pmid = 34680948 | pmc = 8535591 | doi = 10.3390/genes12101553 | doi-access = free }} Together they play an essential role in proliferation, survival, regulation of cell growth and affect almost every organ system in the body.{{cite journal | vauthors = Annunziata M, Granata R, Ghigo E | title = The IGF system | journal = Acta Diabetologica | volume = 48 | issue = 1 | pages = 1–9 | date = March 2011 | pmid = 21042815 | doi = 10.1007/s00592-010-0227-z | s2cid = 24843614 }}

Similarly to IGF-1, IGF-2 is mainly produced in the liver and after it is released into circulation, it stimulates growth and cell proliferation. IGF-2 is thought to be a fetal growth factor, as it is essential for a normal embryonic development and is highly expressed in embryonic and neonatal tissues.{{cite book | vauthors = Winston BW, Ni A, Aurora RC | chapter = Insulin-like Growth Factors | veditors = Laurent GJ, Shapiro SD | title = Encyclopedia of Respiratory Medicine |date=2006 |pages=339–346 |doi=10.1016/B0-12-370879-6/00453-1 | isbn = 978-0-12-370879-3 | quote = GF-II appears to be essential for normal embryonic development and, as such, IGF-II is thought to be a fetal growth factor. IGF-II is highly expressed in embryonic and neonatal tissues and promotes proliferation of many cell types primarily of fetal origin. }}

= Variants =

A splice variant of IGF-1 sharing an identical mature region, but with a different E domain is known as mechano-growth factor (MGF).{{cite journal | vauthors = Carpenter V, Matthews K, Devlin G, Stuart S, Jensen J, Conaglen J, Jeanplong F, Goldspink P, Yang SY, Goldspink G, Bass J, McMahon C | title = Mechano-growth factor reduces loss of cardiac function in acute myocardial infarction | journal = Heart, Lung & Circulation | volume = 17 | issue = 1 | pages = 33–39 | date = February 2008 | pmid = 17581790 | doi = 10.1016/j.hlc.2007.04.013 }}

Related disorders

= Laron syndrome =

= Acromegaly =

Acromegaly is a syndrome caused by the anterior pituitary gland producing excess growth hormone (GH).{{Cite web |title=Acromegaly - NIDDK |url=https://www.niddk.nih.gov/health-information/endocrine-diseases/acromegaly |access-date=2024-05-11 |website=National Institute of Diabetes and Digestive and Kidney Diseases |language=en-US}} A number of disorders may increase the pituitary's GH output, although most commonly it involves a tumor called pituitary adenoma, derived from a distinct type of cell (somatotrophs). It leads to anatomical changes and metabolic dysfunction caused by elevated GH and IGF-1 levels.{{cite journal | vauthors = Giustina A, Chanson P, Kleinberg D, Bronstein MD, Clemmons DR, Klibanski A, van der Lely AJ, Strasburger CJ, Lamberts SW, Ho KK, Casanueva FF, Melmed S | title = Expert consensus document: A consensus on the medical treatment of acromegaly | journal = Nature Reviews. Endocrinology | volume = 10 | issue = 4 | pages = 243–248 | date = April 2014 | pmid = 24566817 | doi = 10.1038/nrendo.2014.21 | doi-access = free }}

High level of IGF-1 in acromegaly is related to an increased risk of some cancers, particularly colon cancer and thyroid cancer.{{cite journal | vauthors = AlDallal S | title = Acromegaly: a challenging condition to diagnose | journal = International Journal of General Medicine | volume = 11 | pages = 337–343 | date = August 2018 | pmid = 30197531 | pmc = 6112775 | doi = 10.2147/IJGM.S169611 | doi-access = free | department = review }}

Use as a diagnostic test

= Growth hormone deficiency =

IGF-1 levels can be analyzed and used by physicians as a screening test for growth hormone deficiency (GHD),{{cite journal | vauthors = Shen Y, Zhang J, Zhao Y, Yan Y, Liu Y, Cai J | title = Diagnostic value of serum IGF-1 and IGFBP-3 in growth hormone deficiency: a systematic review with meta-analysis | journal = European Journal of Pediatrics | volume = 174 | issue = 4 | pages = 419–427 | date = April 2015 | pmid = 25213432 | doi = 10.1007/s00431-014-2406-3 }} acromegaly and gigantism.{{cite journal | vauthors = Trivellin G, Daly AF, Faucz FR, Yuan B, Rostomyan L, Larco DO, Schernthaner-Reiter MH, Szarek E, Leal LF, Caberg JH, Castermans E, Villa C, Dimopoulos A, Chittiboina P, Xekouki P, Shah N, Metzger D, Lysy PA, Ferrante E, Strebkova N, Mazerkina N, Zatelli MC, Lodish M, Horvath A, de Alexandre RB, Manning AD, Levy I, Keil MF, Sierra M, Palmeira L, Coppieters W, Georges M, Naves LA, Jamar M, Bours V, Wu TJ, Choong CS, Bertherat J, Chanson P, Kamenický P, Farrell WE, Barlier A, Quezado M, Bjelobaba I, Stojilkovic SS, Wess J, Costanzi S, Liu P, Lupski JR, Beckers A, Stratakis CA | title = Gigantism and acromegaly due to Xq26 microduplications and GPR101 mutation | journal = The New England Journal of Medicine | volume = 371 | issue = 25 | pages = 2363–2374 | date = December 2014 | pmid = 25470569 | pmc = 4291174 | doi = 10.1056/NEJMoa1408028 }} However, IGF-1 has been shown to be a bad diagnostic screening test for growth hormone deficiency.{{cite journal | vauthors = Iwayama H, Kitagawa S, Sada J, Miyamoto R, Hayakawa T, Kuroyanagi Y, Muto T, Kurahashi H, Ohashi W, Takagi J, Okumura A | title = Insulin-like growth factor-1 level is a poor diagnostic indicator of growth hormone deficiency | journal = Scientific Reports | volume = 11 | issue = 1 | pages = 16159 | date = August 2021 | pmid = 34373538 | pmc = 8352887 | doi = 10.1038/s41598-021-95632-0 | bibcode = 2021NatSR..1116159I }}{{cite journal | vauthors = Fatani TH | title = Diagnostic Value of IGF-1 in Growth Hormone-Deficient Children: Is a Second Growth Hormone Stimulation Test Necessary? | journal = Journal of the Endocrine Society | volume = 7 | issue = 4 | pages = bvad018 | date = February 2023 | pmid = 36846213 | pmc = 9954969 | doi = 10.1210/jendso/bvad018 | doi-access = free }}

The ratio of IGF-1 and insulin-like growth factor-binding protein 3 has been shown to be a useful diagnostic test for GHD.{{cite journal | vauthors = Haj-Ahmad LM, Mahmoud MM, Sweis NW, Bsisu I, Alghrabli AM, Ibrahim AM, Zayed AA | title = Serum IGF-1 to IGFBP-3 Molar Ratio: A Promising Diagnostic Tool for Growth Hormone Deficiency in Children | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 108 | issue = 4 | pages = 986–994 | date = March 2023 | pmid = 36251796 | doi = 10.1210/clinem/dgac609 }}{{cite journal | vauthors = Lambrecht N | title = IGF-1/IGFBP-3 Serum Ratio as a Robust Measure to Determine GH Deficiency and Guide Human Recombinant GH Therapy | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 108 | issue = 4 | pages = e54–e55 | date = March 2023 | pmid = 36454697 | doi = 10.1210/clinem/dgac687 }}

= Liver fibrosis =

Low serum IGF-1 levels have been suggested as a biomarker for predicting fibrosis, but not steatosis, in people with metabolic dysfunction–associated steatotic liver disease.{{cite journal |vauthors=Marques V, Afonso MB, Bierig N, Duarte-Ramos F, Santos-Laso Á, Jimenez-Agüero R, Eizaguirre E, Bujanda L, Pareja MJ, Luís R, Costa A, Machado MV, Alonso C, Arretxe E, Alustiza JM, Krawczyk M, Lammert F, Tiniakos DG, Flehmig B, Cortez-Pinto H, Banales JM, Castro RE, Normann A, Rodrigues CM |date=2021-06-23 |title=Adiponectin, Leptin, and IGF-1 Are Useful Diagnostic and Stratification Biomarkers of NAFLD |journal=Frontiers in Medicine |language=English |volume=8 |pages=683250 |doi=10.3389/fmed.2021.683250 |pmc=8260936 |pmid=34249975 |doi-access=free}}

Causes of elevated IGF-1 levels

Medical conditions:
acromegaly (especially when GH is also high)
delayed puberty{{cite journal |vauthors=Imran SA, Pelkey M, Clarke DB, Clayton D, Trainer P, Ezzat S |date=2010 |title=Spuriously Elevated Serum IGF-1 in Adult Individuals with Delayed Puberty: A Diagnostic Pitfall |department=primary |journal=International Journal of Endocrinology |volume=2010 |pages=1–4 |doi=10.1155/2010/370692 |pmc=2939391 |pmid=20862389 |doi-access=free}}
pregnancy{{cite journal |vauthors=Freda PU |date=August 2009 |title=Monitoring of acromegaly: what should be performed when GH and IGF-1 levels are discrepant? |department=review |journal=Clinical Endocrinology |volume=71 |issue=2 |pages=166–170 |doi=10.1111/j.1365-2265.2009.03556.x |pmc=3654652 |pmid=19226264}}
hyperthyroidism
some rare tumors, such as carcinoids, secreting IGF-1{{cite journal |vauthors=Phillips JD, Yeldandi A, Blum M, de Hoyos A |date=October 2009 |title=Bronchial carcinoid secreting insulin-like growth factor-1 with acromegalic features |department=primary |journal=The Annals of Thoracic Surgery |volume=88 |issue=4 |pages=1350–1352 |doi=10.1016/j.athoracsur.2009.02.042 |pmid=19766843}}
Diet:
High-protein diet{{cite journal | vauthors = Kazemi A, Speakman JR, Soltani S, Djafarian K | title = Effect of calorie restriction or protein intake on circulating levels of insulin like growth factor I in humans: A systematic review and meta-analysis | journal = Clinical Nutrition | volume = 39 | issue = 6 | pages = 1705–1716 | date = June 2020 | pmid = 31431306 | doi = 10.1016/j.clnu.2019.07.030}}
consumption of dairy products (except for cheese){{cite journal|author=Watling CZ, Kelly RK, Tong TYN, Piernas C, Watts EL, Tin Tin S, Knuppel A, Schmidt JA, Travis RC, Key TJ, Perez-Cornago A.|year=2023|title=Associations between food group intakes and circulating insulin-like growth factor-I in the UK Biobank: a cross-sectional analysis|journal=European Journal of Nutrition|volume=62|issue=1|pages=115–124|doi=10.1007/s00394-022-02954-4|pmid=35906357|pmc=9899744}}
consumption of fish
IGF-1 assay problems

Calorie restriction has been found to have no effect on IGF-1 levels.

Causes of reduced IGF-1 levels

Metabolic dysfunction–associated steatotic liver disease, especially at advanced stages of steatohepatitis and fibrosis{{cite journal | vauthors = Ma IL, Stanley TL | title = Growth hormone and nonalcoholic fatty liver disease | journal = Immunometabolism | volume = 5 | issue = 3 | pages = e00030 | date = July 2023 | pmid = 37520312 | pmc = 10373851 | doi = 10.1097/IN9.0000000000000030 }}

Health effects

= Mortality =

Both high and low levels of IGF‐1 increase mortality risk, with the mid‐range (120–160 ng/ml) being associated with the lowest mortality.{{cite journal | vauthors = Rahmani J, Montesanto A, Giovannucci E, Zand H, Barati M, Kopchick JJ, Mirisola MG, Lagani V, Bawadi H, Vardavas R, Laviano A, Christensen K, Passarino G, Longo VD | title = Association between IGF-1 levels ranges and all-cause mortality: A meta-analysis | journal = Aging Cell | volume = 21 | issue = 2 | pages = e13540 | date = February 2022 | pmid = 35048526 | pmc = 8844108 | doi = 10.1111/acel.13540 | author-link14 = Valter Longo }}

== Dairy consumption ==

It has been suggested that consumption of IGF-1 in dairy products could increase cancer risk, particularly prostate cancer.{{cite journal | vauthors = Harrison S, Lennon R, Holly J, Higgins JP, Gardner M, Perks C, Gaunt T, Tan V, Borwick C, Emmet P, Jeffreys M, Northstone K, Rinaldi S, Thomas S, Turner SD, Pease A, Vilenchick V, Martin RM, Lewis SJ | title = Does milk intake promote prostate cancer initiation or progression via effects on insulin-like growth factors (IGFs)? A systematic review and meta-analysis | journal = Cancer Causes & Control | volume = 28 | issue = 6 | pages = 497–528 | date = June 2017 | pmid = 28361446 | pmc = 5400803 | doi = 10.1007/s10552-017-0883-1 }}{{cite web | url = https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/803090/COC_2018_S01_IGF-1_COC_Statement.pdf | title = Statement on possible carcinogenic hazard to consumers from insulin-like growth factor-1 (IGF-1) in the diet | work = assets.publishing.service.gov.uk | access-date = 4 February 2023 }} However, significant levels of intact IGF-1 from oral consumption are not absorbed as they are digested by gastric enzymes.{{cite journal |vauthors=Juskevich JC, Guyer CG|title=Bovine Growth Hormone: Human Food Safety Evaluation |journal=Science |volume=249 |issue=4971 |pages=875–84 |date=August 1990 |pmid=2203142 |doi= 10.1126/science.2203142|jstor=2877952}} IGF-1 present in food is not expected to be active within the body in the way that IGF-1 is produced by the body itself.

The Food and Drug Administration has stated that IGF-I concentrations in milk are not significant when evaluated against concentrations of IGF-I endogenously produced in humans.{{Cite web|date=2000|title=FDA rejects petition to ban rBST|url=https://www.avma.org/javma-news/2000-06-15/fda-rejects-petition-ban-rbst|website=American Veterinary Medical Association|language=en-GB|archive-date=August 13, 2020|archive-url=https://web.archive.org/web/20200813180950/https://www.avma.org/javma-news/2000-06-15/fda-rejects-petition-ban-rbst|url-status=live}}

A 2018 review by the Committee on Carcinogenicity of Chemicals in Food, Consumer Products and the Environment (COC) concluded that there is "insufficient evidence to draw any firm conclusions as to whether exposure to dietary IGF-1 is associated with an increased incidence of cancer in consumers". Certain dairy processes such as fermentation are known to significantly decrease IGF-1 concentrations.{{cite journal | vauthors = Meyer Z, Höflich C, Wirthgen E, Olm S, Hammon HM, Hoeflich A | title = Analysis of the IGF-system in milk from farm animals - Occurrence, regulation, and biomarker potential | journal = Growth Hormone & IGF Research | volume = 35 | issue = | pages = 1–7 | date = August 2017 | pmid = 28544872 | doi = 10.1016/j.ghir.2017.05.004 | doi-access = free }} The British Dietetic Association has described the idea that milk promotes hormone related cancerous tumor growth as a myth, stating "no link between dairy containing diets and risk of cancer or promoting cancer growth as a result of hormones".{{Cite web|date=2024|title=Cancer Diets: Myths and More|url=https://www.bda.uk.com/resource/cancer-diets-myths-and-more.html|website=British Dietetic Association|language=en-GB|archive-date=July 26, 2024|archive-url=https://web.archive.org/web/20240726215251/https://www.bda.uk.com/resource/cancer-diets-myths-and-more.html|url-status=live}}

= Cardiovascular disease =

Increased IGF-1 levels are associated with a 16% lower risk of cardiovascular disease and a 28% reduction of cardiovascular events.{{cite journal | vauthors = Li T, Zhao Y, Yang X, Feng Y, Li Y, Wu Y, Zhang M, Li X, Hu H, Zhang J, Yuan L, Liu Y, Sun X, Qin P, Chen C, Hu D | title = Association between insulin-like growth factor-1 and cardiovascular events: a systematic review and dose-response meta-analysis of cohort studies | journal = Journal of Endocrinological Investigation | volume = 45 | issue = 12 | pages = 2221–2231 | date = December 2022 | pmid = 35596917 | doi = 10.1007/s40618-022-01819-1 | s2cid = 248924624 }}

= Diabetes =

Low IGF-1 levels are shown to increase the risk of developing type 2 diabetes and insulin resistance.{{cite journal | vauthors = Biadgo B, Tamir W, Ambachew S | title = Insulin-like Growth Factor and its Therapeutic Potential for Diabetes Complications - Mechanisms and Metabolic Links: A Review | journal = The Review of Diabetic Studies | volume = 16 | issue = 1 | pages = 24–34 | date = 2021-05-01 | pmid = 33905470 | pmc = 9380093 | doi = 10.1900/RDS.2020.16.24 | doi-broken-date = 1 November 2024 }} On the other hand, a high IGF-1 bioavailability in people with diabetes may delay or prevent diabetes-associated complications, as it improves impaired small blood vessel function.

IGF-1 has been characterized as an insulin sensitizer.{{cite journal |vauthors=Yuen KC, Dunger DB |date=January 2007 |title=Therapeutic aspects of growth hormone and insulin-like growth factor-I treatment on visceral fat and insulin sensitivity in adults |journal=Diabetes, Obesity & Metabolism |volume=9 |issue=1 |pages=11–22 |doi=10.1111/j.1463-1326.2006.00591.x |pmid=17199714}}

Low serum IGF‐1 levels can be considered an indicator of liver fibrosis in type 2 diabetes mellitus patients.{{cite journal | vauthors = Miyauchi S, Miyake T, Miyazaki M, Eguchi T, Niiya T, Yamamoto S, Senba H, Furukawa S, Matsuura B, Hiasa Y | title = Insulin-like growth factor-1 is inversely associated with liver fibrotic markers in patients with type 2 diabetes mellitus | journal = Journal of Diabetes Investigation | volume = 10 | issue = 4 | pages = 1083–1091 | date = July 2019 | pmid = 30592792 | pmc = 6626962 | doi = 10.1111/jdi.13000 }}