Download PDF
Horm Metab Res 2016; 48(05): 299-305
DOI: 10.1055/s-0035-1569277
Endocrine Care
© Georg Thieme Verlag KG Stuttgart · New York

Evolution of Glucose Tolerance After Treatment of Acromegaly: A Study in 57 Patients

C. Jonas
1   Division of Endocrinology and Nutrition, Cliniques universitaires St Luc, Université catholique de Louvain, Brussels, Belgium
,
D. Maiter
1   Division of Endocrinology and Nutrition, Cliniques universitaires St Luc, Université catholique de Louvain, Brussels, Belgium
,
O. Alexopoulou
1   Division of Endocrinology and Nutrition, Cliniques universitaires St Luc, Université catholique de Louvain, Brussels, Belgium
› Author Affiliations
Further Information

Publication History

received 04 September 2015

accepted 11 November 2015

Publication Date:
05 February 2016 (online)

Also available at
    Permissions and Reprints

Abstract

The aim of our study was to evaluate the evolution of glucose metabolism in 57 patients after treatment of their acromegaly and to determine risk factors for the persistence of abnormal glucose tolerance. Therefore, we performed IGF-I measurements, oral glucose tolerance tests (OGTTs), and HOMA to evaluate insulin sensitivity (HOMA-S) and β-cell function (HOMA-β) at diagnosis and at last visit (median follow-up 7 years). At diagnosis of acromegaly, 14 patients (25%) were diabetic and 15 (26%) had impaired glucose tolerance, whereas at the last visit, 32% were diabetic and 26% remained glucose intolerant. There was a decrease in fasting glucose (median − 7.0 mg/dl) in the 20 patients cured by surgery, whereas it increased in the 28 patients controlled under medical therapy (median + 2.0 mg/dl; p<0.05 vs. cured group) and in the 9 patients with active disease (median + 4.0 mg/dl). Loss of β-cell function was more pronounced in the patients under medical treatment (median − 87.9%) vs. the cured group (median − 30.4%; p<0.05). There was a decrease in HbA1c between diagnosis and last visit in patients under pegvisomant (mean − 19.2 mmol/mol) vs. a small increase in patient treated by somatostatin analogues (+ 3.4 mmol/mol; p<0.05). Independent risk factors for persistent abnormal glucose tolerance were the glucose tolerance status at diagnosis and ongoing treatment with somatostatin analogues. In conclusion, we found that more than 50% of patients still have IGT or diabetes after treatment of acromegaly. Improvement of glucose metabolism is mainly observed in cured patients and in patients treated with pegvisomant.

Key words

acromegaly - insulin-growth factor-I - growth hormone - diabetes - glucose - HOMA - OGTT

Supporting Information

 

  • References

  • 1 Kasayama S, Otsuki M, Takagi M, Saito H, Sumitani S, Kouhara H, Koga M, Saitoh Y, Ohnishi T, Arita N. Impaired betacell function in the presence of reduced insulin sensitivity determines glucose tolerance status in acromegalic patients. Clin Endocrinol (Oxf) 2000; 52: 549-555
    CrossrefPubMedGoogle Scholar
  • 2 Kreze A, Kreze-Spirova E, Mikulecky M. Risk factors for glucose intolerance in active acromegaly. Braz J Med Biol Res 2001; 34: 1429-1433
    PubMedGoogle Scholar
  • 3 Alexopoulou O, Bex M, Kameniky P, Bessomo Mvoula A, Chanson P, Maiter D. Prevalence and risk factors of impaired glucose tolerance and diabetes mellitus at diagnosis of acromegaly: a study in 148 patients. Pituitary 2014; 17: 81-89
    CrossrefPubMedGoogle Scholar
  • 4 Colao A, Ferone D, Marzullo P, Lombardi G. Systemic complications of acromegaly: epidemiology, pathogenesis, and management. Endocr Rev 2004; 25: 102-152
    CrossrefPubMedGoogle Scholar
  • 5 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
  • 6 Reid TJ, Post KD, Bruce JN, Nabi KM, Reyes-Vidal CM, Freda PU. Features at diagnosis of 324 patients with acromegaly did not change from 1981 to 2006: acromegaly remains under-recognized and under-diagnosed. Clin Endocrinol (Oxf) 2010; 72: 203-208
    CrossrefPubMedGoogle Scholar
  • 7 Arosio M, Reimondo G, Malchiodi E, Berchialla P, Borraccino A, De Marinis L, Pivonello R, Grottoli S, Losa M, Cannavo S, Minuto F, Montini M, Bondanelli M, De Menis E, Martini C, Angeletti G, Velardo A, Peri A, Faustini-Fustini M, Tita P, Pigliaru F, Borretta G, Scaroni C, Bazzoni N, Bianchi A, Appetecchia M, Cavagnini F, Lombardi G, Ghigo E, Beck-Peccoz P, Colao A, Terzolo M. Predictors of morbidity and mortality in acromegaly: an Italian survey. Eur J Endocrinol 2012; 167: 189-198
    PubMedGoogle Scholar
  • 8 Bex M, Abs R, T’sjoen G, Mockel J, Velkeniers B, Muermans K, Maiter D. AcroBel–the Belgian registry on acromegaly: a survey of the ‘real-life’ outcome in 418 acromegalic subjects. Eur J Endocrinol 2007; 157: 399-409
    CrossrefPubMedGoogle Scholar
  • 9 Serri O, Beauregard C, Hardy J. Long-term biochemical status and disease-related morbidity in 53 postoperative patients with acromegaly. J Clin Endocrinol Metab 2004; 89: 658-661
    CrossrefPubMedGoogle Scholar
  • 10 Jaffrain-Réa ML, Minniti G, Moroni C, Esposito V, Ferretti E, Santoro A, Infusino T, Tamburrano G, Cantore G, Cassone R. Impact of successful transsphenoidal surgery on cardiovascular risk factors in acromegaly. Eur J Endocrinol 2003; 148: 193-201
    CrossrefPubMedGoogle Scholar
  • 11 Colao AM, Auriemma RS, Galderio M, Cappabianca P, Cavallo LM, Esposito F, Grasso LFS, Lombardi G, Pivonello R. Impact of somatostatin analogs versus surgery on glucose metabolism in acromegaly: results of a 5-year observational, open, prospective study. J Clin Endocrinol Metab 2009; 94: 528-537
    CrossrefPubMedGoogle Scholar
  • 12 Tzanela M, Vassiliadi DA, Gavalas N, Szabo A, Margelou E, Valatsou A, Vassilopoulos C. Glucose homeostasis in patients with acromegaly treated with surgery or somatostatin analogues. Clin Endocrinol (Oxf) 2011; 75: 96-102
    CrossrefPubMedGoogle Scholar
  • 13 Urbani C, Saedella C, Calevro A, Rossi G, Scattina I, Lombardi M, Lupi I, Manetti L, Martino E, Bogazzi F. Effects of medical therapies for acromegaly on glucose metabolism. Eur J Endocrinol 2013; 169: 99-108
    CrossrefPubMedGoogle Scholar
  • 14 Stelmachowska-Banas M, Zielinski G, Zdunowski P, Podgorski J, Zgliczynski W. Impact of transsphenoidal surgery on glucose homeostasis and insulin resistance in acromegaly. Neurol Neurochir Pol 2011; 45: 328-334
    PubMedGoogle Scholar
  • 15 Madsen M, Poulsen PL, Orskov H, Moller N, Jorgensen JO. Cotreatment with pegvisomant and somatostatin analog (SA) in SA-responsive acromegalic patients. J Clin Endocrinol Metab 2011; 98: 2405-2413
    PubMedGoogle Scholar
  • 16 Rodrigues TC, Costenaro F, Fedrizzi D, Oliveira MD, de Lima PB, Boschi V, Czepielewski MA. Diabetes mellitus in a cohort of patients with acromegaly. Arq Bras Endocrinol Metab 2011; 55: 714-719
    PubMedGoogle Scholar
  • 17 Steffin B, Gutt B, Bidlingmaier M, Dieterle C, Oltmann F, Schopohl J. Effects of the long-acting somatostatin analogue Lanreotide Autogel on glucose tolerance and insulin resistance in acromegaly. Eur J Endocrinol 2006; 155: 73-78
    CrossrefPubMedGoogle Scholar
  • 18 Levy JC, Matthews DR, Hermans MP. Correct Homeostasis model assessment (HOMA) evaluation uses the computer programm. Diabetes Care 1998; 21: 2191-2192
    CrossrefPubMedGoogle Scholar
  • 19 American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care 2014; 37: s81-s90
    CrossrefPubMedGoogle Scholar
  • 20 Melmed S, Casanueva FF, Klibanski A, Bronstein MD, Chanson P, Lamberts SW, Strasburger CJ, Wass JA, Giustina A. A consensus on the diagnosis and treatment of acromegaly complications. Pituitary 2013; 16: 294-302
    CrossrefPubMedGoogle Scholar
  • 21 Melmed S, Colao AM, Barkan A, Molitch M, Grossman AB, Kleinberg D, Clemmons D, Chanson P, Laws E, Schlechte J, Vance ML, Ho K, Giustina A. Guidelines for acromegaly management: an update. J Clin Endocrinol Metab 2009; 94: 1509-1517
    CrossrefPubMedGoogle Scholar
  • 22 Giustina A, Chanson P, Bronstein MD, Klibanski A, Lamberts S, Casanueva FF, Trainer P, Ghigo E, Ho K, Melmed S. A consensus on criteria for cured acromegaly. J Clin Endocrinol Metab 2010; 95: 3141-3148
    Google Scholar
  • 23 Brabant G, von zur Mühlen A, Wuster C, Ranke MB, Kratzsch J, Kiess W, Ketelslegers JM, Wilhelmsen L, Hulthen L, Saller B, Mattsson A, Wilde J, Schemer R, Kann P. Serum insulin-like growth factor I reference values for an automated chemiluminescence immunoassay system: results from a multicenter study. Horm Res 2003; 60: 53-60
    CrossrefPubMedGoogle Scholar
  • 24 Puder JJ, Nilavar S, Post KD, Freda PU. Relationship between disease-related morbidity and biochemical markers of activity in patients with acromegaly. J Clin Endocrinol Metab 2005; 90: 1972-1978
    CrossrefPubMedGoogle Scholar
  • 25 Espinosa-de-Los-Monteros AL, Gonzalez 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
  • 26 Colao AM, Auriemma RS, Savastano S, Galderio M, Grasso LFS, Lombardi G, Pivonello R. Glucose tolerance and somaostatin analog treatment in acromegaly: a 12-month study. J Clin Endocrinol Metab 2009; 94: 2907-2914
    CrossrefPubMedGoogle Scholar
  • 27 Petrossians P, Tichomirowa MA, Stevenaert A, Martin D, Daly AF, Beckers A. The Liege Acromegaly Survey (LAS): a new software tool for the study of acromegaly. Ann Endocrinol (Paris) 2012; 73: 190-201
    CrossrefPubMedGoogle Scholar
  • 28 Couture E, Bongard V, Maiza JC, Bennet A, Caron P. Glucose status in patients with acromegaly receiving primary treatment with the somatostatin analog lanreotide. Pituitary 2012; 15: 518-525
    CrossrefPubMedGoogle Scholar
  • 29 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 if pancreatic beta-cell function is preserved. Eur J Endocrinol 2011; 164: 467-473
    CrossrefPubMedGoogle Scholar
  • 30 Cheng S, Al-Agha R, Araujo PB, Serri O, Asa LS, Ezzat S. Metabolic glucose status and pituitary pathology portend therapeutic outcomes in acromegalic. PloS One 2013; e73543
    PubMedGoogle Scholar
  • 31 Diabetes Atlas. www.idf.org/diabetesatlas (Accessed 13/03/2014)
    PubMed
  • 32 Clemmons DR. Roles of insulin-like growth factor-I and growth hormone in mediating insulin resistance in acromegaly. Pituitary 2002; 5: 181-183
    CrossrefPubMedGoogle Scholar
  • 33 Dominici FP, Argentino DP, Munoz MC, Miquet JG, Sotelo AI, Turyn D. Influence of the crosstalk between growth hormone and insulin signelling on the modulation of the insulin sensitivity. Growth Horm IGF Res 2005; 15: 324-336
    CrossrefPubMedGoogle Scholar
  • 34 Nielsen JH, Linde S, Welinder BS, Billestrup N, Madsen OD. Growth hormone is a growth factor for the differentiated pancreatic beta-cell. Mol Endocrinol 1989; 3: 165-173
    CrossrefPubMedGoogle Scholar
  • 35 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
  • 36 Alexopoulou O, Bex M, Abs R, T’sjoen G, Velkeniers B, Maiter D. Divergence between growth hormone and insulin-like growth factor-i concentrations in the follow-up of acromegaly. J Clin Endocrinol Metab 2008; 93: 1324-1330
    CrossrefPubMedGoogle Scholar
  • 37 Baldelli R, Battista C, Leonetti F, Ghiggi MR, Ribaudo MC, Paoloni A, D’Amico E, Ferretti E, Baratta R, Liuzzi A, Trischitta V, Tamburrano G. Glucose homeostasis in acromegaly: effects of long-acting somatostatin analogues treatment. Clin Endocrinol 2003; 59: 492-499
    CrossrefPubMedGoogle Scholar
  • 38 Mazziotti G, Floriani I, Bonadonna S, Torri V, Chanson P, Giustina A. Effects of somatostatin analogs on glucose homeostasis: a metaanalysis of acromegaly studies. J Clin Endocrinol Metab 2009; 94: 1500-1508
    CrossrefPubMedGoogle Scholar
  • 39 Linberg-Larsen R, Moller N, Schmitz O, Nielsen S, Andersen M, Orskov H, Jorgensen JO. The impact of pegvisomant treatment on substrate metabolism and insulin sensitivity in patients with acromegaly. J Clin Endocrinol Metab 2007; 92: 1724-1728
    CrossrefPubMedGoogle Scholar
  • 40 Drake WM, Rowles SV, Roberts ME, Fode FK, Besser GM, Monson JP, Trainer PJ. Insulin sensitivity and glucose tolerance improve in patients with acromegaly converted from depot octreotide to pegvisomant. Eur J Endocrinol 2003; 149: 521-527
    CrossrefPubMedGoogle Scholar
  • 41 Higham CE, Rowles S, Russell-Jones D, Umpleby AM, Trainer PJ. Pegvisomant improves insulin sensitivity and reduces overnight free fatty acid concentrations in patients with acromegaly. J Clin Endocrinol Metab 2009; 94: 2459-2463
    CrossrefPubMedGoogle Scholar
  • 42 Barkan AL, Burman P, Clemmons DR, Drake WM, Gagel RF, Harris PE, Trainer PJ, van der Lely AJ, Vance ML. Glucose homeostasis and safety in patients with acromegaly converted from long-acting octreotide to pegvisomant. J Clin Endocrinol Metab 2005; 90: 5684-5691
    CrossrefPubMedGoogle Scholar
  • 43 Colao A, Pivonello R, Auriemma RS, De Martino MC, Bidlingmaier M, Briganti F, Tortora F, Burman P, Kourides IA, Strasburger CJ, Lombardi G. Efficacy of 12-month treatment with the GH receptor antagonist pegvisomant in patients with acromegaly resistant to long-term, high-dose somatostatin analog treatment: effect on IGF-I levels, tumor mass, hypertension and glucose tolerance. Eur J Endocrinol 2006; 154: 467-477
    CrossrefPubMedGoogle Scholar