{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T14:17:21Z","timestamp":1784557041085,"version":"3.55.0"},"reference-count":20,"publisher":"Bioscientifica","content-domain":{"domain":["edm.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2013,9,1]]},"abstract":"Summary<\/jats:title>\n \n A state of insulin resistance is common to the clinical conditions of both chronic growth hormone (GH) deficiency and GH excess (acromegaly). GH has a physiological role in glucose metabolism in the acute settings of fast and exercise and is the only anabolic hormone secreted in the fasting state. We report the case of a patient in whom knowledge of this aspect of GH physiology was vital to her care. A woman with well-controlled type 1 diabetes mellitus who developed hypopituitarism following the birth of her first child required GH replacement therapy. Hours after the first dose, she developed a rapid metabolic deterioration and awoke with hyperglycaemia and ketonuria. She adjusted her insulin dose accordingly, but the pattern was repeated with each subsequent increase in her dose. Acute GH-induced lipolysis results in an abundance of free fatty acids (FFA); these directly inhibit glucose uptake into muscle, and this can lead to hyperglycaemia. This glucose\u2013fatty acid cycle was first described by Randle\n et al<\/jats:italic>\n . in 1963; it is a nutrient-mediated fine control that allows oxidative muscle to switch between glucose and fatty acids as fuel, depending on their availability. We describe the mechanism in detail.\n <\/jats:p>\n \n Learning points<\/jats:title>\n \n \n \n There is a complex interplay between GH and insulin resistance: chronically, both GH excess and deficiency lead to insulin resistance, but there is also an acute mechanism that is less well appreciated by clinicians.<\/jats:p>\n <\/jats:list-item>\n \n GH activates hormone-sensitive lipase to release FFA into the circulation; these may inhibit the uptake of glucose leading to hyperglycaemia and ketosis in the type 1 diabetic patient.<\/jats:p>\n <\/jats:list-item>\n \n The Randle cycle, or glucose\u2013fatty acid cycle, outlines the mechanism for this acute relationship.<\/jats:p>\n <\/jats:list-item>\n \n Monitoring the adequacy of GH replacement in patients with type 1 diabetes is difficult, with IGF1 an unreliable marker.<\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1530\/edm-13-0047","type":"journal-article","created":{"date-parts":[[2013,9,30]],"date-time":"2013-09-30T08:59:26Z","timestamp":1380531566000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-2","source":"Crossref","is-referenced-by-count":1,"title":["GH replacement causing acute hyperglycaemia and ketonuria in a type 1 diabetic patient"],"prefix":"10.1530","volume":"2013","author":[{"given":"Dominic","family":"Cavlan","sequence":"first","affiliation":[{"name":"Department of Endocrinology, St Bartholomew's Hospital, West Smithfield, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanti","family":"Vijayaraghavan","sequence":"additional","affiliation":[{"name":"1 Newham University Hospital, Glen Road, London E13 8SL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Gelding","sequence":"additional","affiliation":[{"name":"1 Newham University Hospital, Glen Road, London E13 8SL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Drake","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, St Bartholomew's Hospital, West Smithfield, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"ref41","first-page":"785","article-title":"The glucose fatty-acid cycle. Its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus","volume":"1","year":"1963","journal-title":"Lancet"},{"key":"ref121","doi-asserted-by":"crossref","first-page":"1442","DOI":"10.1210\/jc.2006-1487","article-title":"A 10-year prospective study of the metabolic effects of growth hormone replacement in adults","volume":"92","year":"2007","journal-title":"Journal of Clinical Endocrinology and Metabolism"},{"key":"ref51","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1152\/ajpendo.00093.2009","article-title":"The cycle revisited : a new head for an old hat of and","author":"HueL","year":"2009","journal-title":"American Journal Physiology Endocrinology Metabolism"},{"key":"ref171","doi-asserted-by":"crossref","first-page":"2301","DOI":"10.2337\/diabetes.50.10.2301","article-title":"Pharmacological antilipolysis restores insulin sensitivity during growth hormone exposure","volume":"50","year":"2001","journal-title":"Diabetes"},{"key":"ref181","doi-asserted-by":"crossref","first-page":"1834","DOI":"10.1210\/jc.2006-2659","article-title":"Dose\u2013response effects of free fatty acids on glucose and lipid metabolism during somatostatin blockade of growth hormone and insulin in humans","volume":"92","year":"2007","journal-title":"Journal of Clinical Endocrinology and Metabolism"},{"key":"ref191","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1046\/j.1365-2265.2003.01714.x","article-title":"The effect of growth hormone (GH) replacement therapy in adult patients with type 1 diabetes mellitus and GH deficiency","volume":"58","year":"2003","journal-title":"Clinical Endocrinology"},{"key":"ref91","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1046\/j.1365-2265.2003.01714.x","article-title":"The effect of growth hormone (GH) replacement therapy in adult patients with type 1 diabetes mellitus and GH deficiency","volume":"58","year":"2003","journal-title":"Clinical Endocrinology"},{"key":"ref81","doi-asserted-by":"crossref","first-page":"1834","DOI":"10.1210\/jc.2006-2659","article-title":"Dose\u2013response effects of free fatty acids on glucose and lipid metabolism during somatostatin blockade of growth hormone and insulin in humans","volume":"92","year":"2007","journal-title":"Journal of Clinical Endocrinology and Metabolism"},{"key":"ref111","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1210\/er.2008-0027","article-title":"Effects of growth hormone on glucose, lipid, and protein metabolism in human subjects","volume":"30","year":"2009","journal-title":"Endocrine Reviews"},{"key":"ref01","doi-asserted-by":"crossref","first-page":"1453","DOI":"10.1210\/jc.2003-030218","article-title":"Growth hormone replacement therapy and insulin sensitivity","volume":"88","year":"2003","journal-title":"Journal of Clinical Endocrinology and Metabolism"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"1442","DOI":"10.1210\/jc.2006-1487","article-title":"A 10-year prospective study of the metabolic effects of growth hormone replacement in adults","volume":"92","year":"2007","journal-title":"Journal of Clinical Endocrinology and Metabolism"},{"key":"ref141","first-page":"785","article-title":"The glucose fatty-acid cycle. 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