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Horm Metab Res 2018; 50(05): 408-413
DOI: 10.1055/a-0594-2404
Endocrine Care
© Georg Thieme Verlag KG Stuttgart · New York

Impact of Glucose Metabolism Disorders on IGF-1 Levels in Patients with Acromegaly

Sema Ciftci Dogansen
1   Istanbul University, Istanbul Faculty of Medicine, Division of Endocrinology and Metabolism, Istanbul, Turkey
,
Gulsah Yenidunya Yalin
1   Istanbul University, Istanbul Faculty of Medicine, Division of Endocrinology and Metabolism, Istanbul, Turkey
,
Seher Tanrikulu
1   Istanbul University, Istanbul Faculty of Medicine, Division of Endocrinology and Metabolism, Istanbul, Turkey
,
Sema Yarman
1   Istanbul University, Istanbul Faculty of Medicine, Division of Endocrinology and Metabolism, Istanbul, Turkey
› Author Affiliations
Further Information

Publication History

received 11 June 2017

accepted 07 March 2018

Publication Date:
11 April 2018 (online)

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Abstract

In this study, we aimed to evaluate the presence of glucose metabolism abnormalities and their impact on IGF-1 levels in patients with acromegaly. Ninety-three patients with acromegaly (n=93; 52 males/41 females) were included in this study. Patients were separated into three groups such as; normal glucose tolerance (n=23, 25%), prediabetes (n=38, 41%), and diabetes mellitus (n=32, 34%). Insulin resistance was calculated with homeostasis model assessment (HOMA). HOMA-IR > 2.5 or ≤2.5 were defined as insulin resistant or noninsulin resistant groups, respectively. Groups were compared in terms of factors that may be associated with glucose metabolism abnormalities. IGF-1% ULN (upper limit of normal)/GH ratios were used to evaluate the impact of glucose metabolism abnormalities on IGF-1 levels. Patients with diabetes mellitus were significantly older with an increased frequency of hypertension (p<0.001, p=0.01, respectively). IGF-1% ULN/GH ratio was significantly lower in prediabetes group than in normal glucose tolerance group (p=0.04). Similarly IGF-1% ULN/GH ratio was significantly lower in insulin resistant group than in noninsulin resistant group (p=0.04). Baseline and suppressed GH levels were significantly higher in insulin resistant group than in noninsulin resistant group (p=0.024, p<0.001, respectively). IGF-1% ULN/GH ratio is a useful marker indicating glucose metabolism disorders and IGF-1 levels might be inappropriately lower in acromegalic patients with insulin resistance or prediabetes. We suggest that IGF-1 levels should be re-evaluated after the improvement of insulin resistance or glycemic regulation for the successful management of patients with acromegaly.

Key words

acromegaly - insulin resistance - prediabetes - diabetes mellitus - IGF-1 levels - IGF-1/GH ratio
 

  • References

  • 1 Colao A, Ferone D, Marzullo P, Lombardi G. Systemic complication of acromegaly: Epidemiology, pathogenesis and management. Endocr Rev 2004; 25: 102-152
    CrossrefPubMedGoogle Scholar
  • 2 Møller N, Jørgensen JO. Effects of growth hormone on glucose, lipid and protein metabolism in human subjects. Endocr Rev 2009; 30: 152-177
    CrossrefPubMedGoogle Scholar
  • 3 Kasayama S, Otsuki M, Takagi M, Saito H, Sumitani S, Kouhara H, Koga M, Saitoh Y, Ohnishi T, Arita N. Impaired beta cell function in the presence of reduced insulin sensitivity determines glucose tolerance status in acromegalic patients. Clin Endocrinol (Oxf) 2000; 52: 549-555
    CrossrefPubMedGoogle Scholar
  • 4 Kreze A, Kreze-Spirova E, Mikulecky M. Risk factors for glucose intolerance in active acromegaly. Braz J Med Biol Res 2001; 34: 1429-1433
    CrossrefPubMedGoogle Scholar
  • 5 Stelmachowska-Banas M, Zdunowski P, Zgliczynski W. Abnormalities in glucose homeostasis in acromegaly. Does the prevalence of glucose intolerance depend on the level of activity of the disease and the duration of the symptoms?. Endokrynol Pol 2009; 60: 20-24
    PubMedGoogle Scholar
  • 6 Fieffe S, Morange I, Petrossians P, Chanson P, Rohmer V, Cortet C, Borson-Chazot F, Brue T, Delemer B. Diabetes in acromegaly, prevalence, risk factors, and evolution: Data from the French Acromegaly Registry. Eur J Endocrinol 2011; 164: 877-884
    CrossrefPubMedGoogle Scholar
  • 7 Rodrigues TC, Costenaro F, Fedrizzi D, Oliveira MD, Lima PB, Boschi V, Czepielewski MA. Diabetes mellitus in a cohort of patients with acromegaly. Arq Bras Endocrinol Metabol 2011; 55: 714-719
    CrossrefPubMedGoogle Scholar
  • 8 Espinosa-de-los-Monteros AL, González B, Vargas G, Sosa E, Mercado M. Clinical and biochemical characteristics of acromegalic patients with different abnormalities in glucose metabolism. Pituitary 2011; 14: 231-235
    CrossrefPubMedGoogle Scholar
  • 9 Kim SK, Suh S, Lee JI, Hur KY, Chung JH, Lee MK, Min YK, Kim JH, Kim JH, Kim KW. The Ability of β-Cells to Compensate for Insulin Resistance is Restored with a Reduction in Excess Growth Hormone in Korean Acromegalic Patients. J Korean Med Sci 2012; 27: 177-183
    CrossrefPubMedGoogle Scholar
  • 10 Alexopoulou O, Bex M, Kamenicky P, Mvoula AB, Chanson P, Maiter D. Prevelance and risk factors of impaired glucose tolerance and diabetes mellitus at diagnosis of acromegaly: A study in 148 patients. Pituitary 2013; 17: 81-89
    PubMedGoogle Scholar
  • 11 Park JY, Kim JH, Kim SW, Chung JH, Min YK, Lee MS, Lee MK, Kim KW. Using growth hormone levels to detect macroadenoma in patients with acromegaly. EndocrinolMetab (Seoul) 2014; 29: 450-456
    PubMedGoogle Scholar
  • 12 Mercado M, Gonzalez B, Vargas G, Ramirez C, de los Monteros AL, Sosa E, Jervis P, Roldan P, Mendoza V, López-Félix B, Guinto G. Successful mortality reduction and control of comorbidities in patients with acromegaly followed at a highly specialized multidisciplinary clinic. J Clin Endocrinol Metab 2014; 99: 4438-4446
    CrossrefPubMedGoogle Scholar
  • 13 Suda K, Fukuoka H, Iguchi G, Hirota Y, Nishizawa H, Bando H, Matsumoto R, Takahashi M, Sakaguchi K, Takahashi Y. The prevalence of acromegaly in hospitalized patients with type 2 diabetes. Endocr J 2015; 62: 53-59
    CrossrefPubMedGoogle Scholar
  • 14 Cheng S, Gomez K, Serri O, Chik C, Ezzat S. The role of diabetes in acromegaly associated neoplasia. PLoS One 2015; 21: e0127276
    PubMedGoogle Scholar
  • 15 Portocarrero-Ortiz LA, Vergara-Lopez A, Vidrio-Velazquez M, Uribe-Diaz AM, García-Dominguez A, Reza-Albarrán AA, Cuevas-Ramos D, Melgar V, Talavera J, Rivera-Hernandez AJ, Valencia-Méndez CV, Mercado M. Mexican Acromegaly Registry Group . The Mexican Acromegaly Registry: Clinical and biochemical characteristics at diagnosis and therapeutic outcomes. J Clin Endocrinol Metab 2016; 18: jc20161937
    PubMedGoogle Scholar
  • 16 Frara S, Maffezzoni F, Mazziotti G, Giustina A. Current and Emerging Aspects of Diabetes Mellitus in Acromegaly. Trends Endocrinol Metab 2016; 27: 470-483
    CrossrefPubMedGoogle Scholar
  • 17 Lim DJ, Kwon HS, Cho JH, Kim SH, Choi YH, Yoon KH, Cha BY, Lee KW, Son HY, Kang SK. Acromegaly associated with type 2 diabetes showing normal IGF-1 levels under poorly controlled glycemia. Endocr J 2007; 54: 537-541
    CrossrefPubMedGoogle Scholar
  • 18 Arihara Z, Sakurai K, Yamada S, Murokami O, Takahashi K. Acromegaly with normal IGF-1 levels probably due to poorly controlled diabetes mellitus. Tohoku J Exp Med 2008; 216: 325-329
    CrossrefPubMedGoogle Scholar
  • 19 Lee HM, Lee SH, Yang IH, Hwang IK, Hwang YC, Ahn KJ, Chung HY, Hwang HJ, Jeong IK. Acromegaly with Normal Insulin-Like Growth Factor-1 Levels and Congestive Heart Failure as the First Clinical Manifestation. Endocrinol Metab (Seoul) 2015; 30: 395-401
    CrossrefPubMedGoogle Scholar
  • 20 Wijayaratne DR, Arambewela MH, Dalugama C, Wijesundera D, Somasundaram N, Katulanda P. Acromegaly presenting with low insulin-like growth factor-1 levels and diabetes: a case report. J Med Case Rep 2015; 9: 241
    CrossrefPubMedGoogle Scholar
  • 21 Otsuka F, Ogura T, Yamauchi T, Shikata K, Kageyama J, Makino H. IDDM accompanied by a growth hormone-producing pituitary adenoma. A case report. Diabetes Care 1997; 20: 1838-1841
    CrossrefPubMedGoogle Scholar
  • 22 Yamauchi T, Miyatake T, Ohno Y, Aoki N. Type 1 diabetes associated with asymptomatic acromegaly successfully treated with surgery after pregnancy: a case report. Endocr J 2005; 52: 413-420
    CrossrefPubMedGoogle Scholar
  • 23 Hofmann EA, Polonsky KS, Weiss RE. Diagnosis of acromegaly in a patient with type 1 diabetes mellitus. Endocr Pract 2002; 8: 113-118
    CrossrefPubMedGoogle Scholar
  • 24 Katznelson L, Laws Jr ER, Melmed S, Molitch ME, Murad MH, Utz A, Wass JA. Endocrine Society. Acromegaly: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 2014; 99: 3933-3951
    CrossrefPubMedGoogle Scholar
  • 25 Fukuoka H, Takahashi Y, Iida K, Kudo T, Nishizawa H, Imanaka M, Takeno R, Iguchi G, Takahashi K, Okimura Y, Kaji H, Chihara K. Low serum IGF-I/GH ratio is associated with abnormal glucose tolerance in acromegaly. Horm Res 2008; 69: 165-171
    CrossrefPubMedGoogle Scholar
  • 26 American Diabetes Association . Standards of Medical Care in Diabetes. Classification and diagnosis of diabetes mellitus. Diabetes Care 2016; 39: S13-S23
    CrossrefPubMedGoogle Scholar
  • 27 International Expert Committee . International Expert Committee report on the role of the A1C assay in the diagnosis of diabetes. Diabetes Care 2009; 32: 1327-1334
    CrossrefPubMedGoogle Scholar
  • 28 Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985; 28: 412-419
    CrossrefPubMedGoogle Scholar
  • 29 Ascaso JF, Pardo S, Real JT, Lorente RI, Priego A, Carmena R. Diagnosing insulin resistance by simple quantitative methods in subjects with normal glucose metabolism. Diabetes Care 2003; 26: 3320-3325
    CrossrefPubMedGoogle Scholar
  • 30 Satman I, Omer B, Tutuncu Y, Kalaca S, Gedik S, Dinccag N, Karsidag K, Genc S, Telci A, Canbaz B, Turker F, Yilmaz T, Cakir B, Tuomilehto J. TURDEP-II Study Group . Twelve-year trends in the prevalence and risk factors of diabetes and prediabetes in Turkish adults. Eur J Epidemiol 2013; 28: 169-180
    Google Scholar
  • 31 Dreval AV, Trigolosova IV, Misnikova IV, Kovalyova YA, Tishenina RS, Barsukov IA, Vinogradova AV, Wolffenbuttel BH. Prevalence of diabetes mellitus in patients with acromegaly. Endocr Connect 2014; 3: 93-98
    CrossrefPubMedGoogle Scholar
  • 32 Kinoshita Y, Fujii H, Takeshita A, Taguchi M, Miyakawa M, Oyama K, Yamada S, Takeuchi Y. Impaired glucose metabolism in Japanese patients with acromegaly is restored after successful pituitary surgery ifpancreatic {beta}-cell function is preserved. Eur J Endocrinol 2011; 164: 467-473
    CrossrefPubMedGoogle Scholar
  • 33 Nabarro JD. Acromegaly. Clin Endocrinol 1987; 26: 481-512
    CrossrefPubMedGoogle Scholar
  • 34 Dominici FP, Turyn D. Growth hormone-induced alterations in the insulin-signaling system. Exp Biol Med (Maywood) 2002; 227: 149-157
    CrossrefPubMedGoogle Scholar
  • 35 Higham CE, Rowles S, Russell-Jones D, Umpleby AM, Trainer PJ. Pegvisomant improves insulinsensitivity and reduces overnight free fatty acid concentrations in patients with acromegaly. J Clin Endocrinol Metab. 2009; 94: 2459-2463
    CrossrefPubMedGoogle Scholar
  • 36 Coculescu M, Niculescu D, Lichiardopol R, Purice M. Insulin resistance and insulin secretion in non-diabetic acromegalic patients. Insulin resistance and insulin secretion in non-diabetic acromegalic patients. Exp Clin Endocrinol Diabetes 2007; 115: 308-316
    Article in Thieme ConnectPubMedGoogle Scholar
  • 37 Sonksen PH, Greenwood FC, Ellis JP, Lowy C, Rutherford A, Nabarro JD. Changes of carbohydrate tolerance in acromegaly with progress of the disease and in response to treatment. J Clin Endocrinol Metab 1967; 27: 1418-1430
    CrossrefPubMedGoogle Scholar
  • 38 Wallace TM, Levy JC, Matthews DR. Use and abuse of HOMA modeling. Diabetes Care 2004; 27: 1487-1495
    CrossrefPubMedGoogle Scholar
  • 39 Moses AC, Young SC, Morrow LA, O’Brien M, Clemmons DR. Recombinant human insulin-like growth factor I increases insulin sensitivity and improves glycemic control in type II diabetes. Diabetes 1996; 45: 91-100
    PubMedGoogle Scholar
  • 40 Dominici FP, Argentino DP, Muñoz MC, Miquet JG, Sotelo AI, Turyn D. Influence of the crosstalk between growth hormone and insulin signalling on the modulation of insulin sensitivity. Growth Horm IGF Res 2005; 15: 324-336
    CrossrefPubMedGoogle Scholar
  • 41 O'Connell T, Clemmons DR. IGF-I/IGF-binding protein-3 combination improves insulin resistance by GH-dependent and independent mechanisms. J Clin Endocrinol Metab 2002; 87: 4356-4360
    CrossrefPubMedGoogle Scholar
  • 42 Niculescu D, Purice M, Coculescu M. Insulin-like growth factor-I correlates more closely than growth hormone with insulin resistance and glucose intolerance in patients with acromegaly. Pituitary 2013; 16: 168-174
    CrossrefPubMedGoogle Scholar
  • 43 Barkan AL, Beitins IZ, Kelch RP. Plasma insulin-like growth factor-I/somatomedin-C in acromegaly: correlation with the degree of growth hormone hypersecretion. J Clin Endocrinol Metab 1988; 67: 69-73
    CrossrefPubMedGoogle Scholar
  • 44 Grottoli S, Gasco V, Ragazzoni F, Ghigo E. Hormonal diagnosis of GH hypersecretory states. J Endocrinol Invest 2003; 26 Suppl 27-35
    PubMedGoogle Scholar
  • 45 Herlihy OM, Perros P. Elevated serum growth hormone in a patient with Type 1 diabetes: a diagnostic dilemma. Diabetes Metab Res Rev 2000; 16: 211-216
    CrossrefPubMedGoogle Scholar
  • 46 Clayton KL, Holly JM, Carlsson LM, Jones J, Cheetham TD, Taylor AM, Dunger DB. Loss of the normal relationships between growth hormone, growth hormone-binding protein and insulin-like growth factor-I in adolescents with insulin-dependent diabetes mellitus. Clin Endocrinol (Oxf) 1994; 41: 517-524
    CrossrefPubMedGoogle Scholar
  • 47 Volzke H, Nauck M, Rettig R, Dorr M, Higham C, Brabant G, Wallaschofski H. Association between hepatic steatosis and serum IGF1 and IGFBP-3 levels in a population-based sample. Eur J Endocrinol 2009; 161: 705-713
    CrossrefPubMedGoogle Scholar
  • 48 Sandhu MS, Heald AH, Gibson JM, Cruickshank JK, Dunger DB, Wareham NJ. Circulating concentrations of insulin-like growth factor-I and development of glucose intolerance: A prospective observational study. Lancet 2002; 359: 1740-1745
    CrossrefPubMedGoogle Scholar
  • 49 Petersenn S, Buchfelder M, Gerbert B, Franz H, Quabbe HJ, Schulte HM, Grussendorf M, Reincke M. Participants of the German Acromegaly Register . Age and sex as predictors of biochemical activity in acromegaly: analysis of 1,485 patients from the German Acromegaly Register. Clin Endocrinol (Oxf) 2009; 71: 400-405
    CrossrefPubMedGoogle Scholar