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21.02.2024

Glucose intolerance in acromegaly is driven by low insulin secretion; results from an intravenous glucose tolerance test

verfasst von: Laura Georgiana Zaifu, Dan Alexandru Niculescu, Andreea Elena Kremer, Andra Caragheorgheopol, Mariana Sava, Carmen Nicoleta Iordachescu, Roxana Dusceac, Iulia Florentina Burcea, Catalina Poiana

Erschienen in: Pituitary | Ausgabe 2/2024

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Abstract

Purpose

Insulin sensitivity (S_i) and its role in glucose intolerance of acromegaly has been extensively evaluated. However, data on insulin secretion is limited. We aimed to assess stimulated insulin secretion using an intravenous glucose tolerance test (IVGTT) in active acromegaly.

Methods

We performed an IVGTT in 25 patients with active acromegaly (13 normal glucose tolerance [NGT], 6 impaired glucose tolerance [IGT] and 6 diabetes mellitus [DM]) and 23 controls (8 lean NGT, 8 obese NGT and 7 obese IGT). Serum glucose and insulin were measured at 20 time points along the test to calculate S_i and acute insulin response (AIRg). Medical treatment for acromegaly or diabetes was not allowed.

Results

In acromegaly, patients with NGT had significantly (p for trend < 0.001) higher AIRg (3383 ± 1082 pmol*min/L) than IGT (1215 ± 1069) and DM (506 ± 600). AIRg was higher in NGT (4764 ± 1180 pmol*min/L) and IGT (3183 ± 3261) controls with obesity than NGT (p = 0.01) or IGT (p = 0.17) acromegaly. S_i was not significantly lower in IGT (0.68 [0.37, 0.88] 10⁶*L/pmol*min) and DM (0.60 [0.42, 0.84]) than in NGT (0.81 [0.58, 1.55]) patients with acromegaly. NGT (0.33 [0.30, 0.47] 10⁶*L/pmol*min) and IGT (0.37 [0.21, 0.66]) controls with obesity had lower S_i than NGT (p = 0.001) and IGT (p = 0.43) acromegaly.

Conclusion

We demonstrated that low insulin secretion is the main driver behind glucose intolerance in acromegaly. Compared to NGT and IGT controls with obesity, patients with NGT or IGT acromegaly had higher S_i. Together, these findings suggest that impaired insulin secretion might be a specific mechanism for glucose intolerance in acromegaly.

Gadelha MR, Kasuki L, Lim DST, Fleseriu M (2019) Systemic complications of Acromegaly and the impact of the Current Treatment Landscape: an update. Endocr Rev 40:268–332. https://doi.org/10.1210/er.2018-00115CrossRefPubMed

Melmed S, Kaiser UB, Lopes MB, Bertherat J, Syro LV, Raverot G, Reincke M, Johannsson G, Beckers A, Fleseriu M, Giustina A, Wass JAH, Ho KKY (2022) Clinical Biology of the Pituitary Adenoma. Endocr Rev 43:1003–1037. https://doi.org/10.1210/ENDREV/BNAC010CrossRefPubMedPubMedCentral

Fleseriu M, Langlois F, Lim DST, Varlamov EV, Melmed S (2022) Acromegaly: pathogenesis, diagnosis, and management. Lancet Diabetes Endocrinol 10:804–826. https://doi.org/10.1016/S2213-8587(22)00244-3CrossRefPubMed

Giustina A, Barkhoudarian G, Beckers A, Ben-Shlomo A, Biermasz N, Biller B, Boguszewski C, Bolanowski M, Bollerslev J, Bonert V, Bronstein MD, Buchfelder M, Casanueva F, Chanson P, Clemmons D, Fleseriu M, Formenti AM, Freda P, Gadelha M, Geer E, Gurnell M, Heaney AP, Ho KKY, Ioachimescu AG, Lamberts S, Laws E, Losa M, Maffei P, Mamelak A, Mercado M, Molitch M, Mortini P, Pereira AM, Petersenn S, Post K, Puig-Domingo M, Salvatori R, Samson SL, Shimon I, Strasburger C, Swearingen B, Trainer P, Vance ML, Wass J, Wierman ME, Yuen KCJ, Zatelli MC, Melmed S (2020) Multidisciplinary management of acromegaly: a consensus. Rev Endocr Metab Disord 21:667–678. https://doi.org/10.1007/s11154-020-09588-zCrossRefPubMedPubMedCentral

Giustina A, Barkan A, Beckers A, Biermasz N, Biller BMK, Boguszewski C, Bolanowski M, Bonert V, Bronstein MD, Casanueva FF, Clemmons D, Colao A, Ferone D, Fleseriu M, Frara S, Gadelha MR, Ghigo E, Gurnell M, Heaney AP, Ho K, Ioachimescu A, Katznelson L, Kelestimur F, Kopchick J, Krsek M, Lamberts S, Losa M, Luger A, Maffei P, Marazuela M, Mazziotti G, Mercado M, Mortini P, Neggers S, Pereira AM, Petersenn S, Puig-Domingo M, Salvatori R, Shimon I, Strasburger C, Tsagarakis S, van der Lely AJ, Wass J, Zatelli MC, Melmed S (2020) A consensus on the diagnosis and treatment of acromegaly comorbidities: an update. J Clin Endocrinol Metab 105:E937–E946. https://doi.org/10.1210/clinem/dgz096CrossRef

Frara S, Maffezzoni F, Mazziotti G, Giustina A (2016) Current and emerging aspects of diabetes Mellitus in Acromegaly. Trends Endocrinol Metab 27:470–483. https://doi.org/10.1016/j.tem.2016.04.014CrossRefPubMed

Albertelli M, Nazzari E, Dotto A, Grasso LF, Sciallero S, Pirchio R, Rebora A, Boschetti M, Pivonello R, Ricci Bitti S, Colao AAL, Ferone D (2021) Possible protective role of metformin therapy on colonic polyps in acromegaly: an exploratory cross-sectional study. Eur J Endocrinol 184:423–429. https://doi.org/10.1530/EJE-20-0795CrossRef

Moustaki M, Paschou SA, Xekouki P, Kotsa K, Peppa M, Psaltopoulou T, Kalantaridou S, Vryonidou A (2023) Secondary diabetes mellitus in acromegaly. Endocrine 81:1–15. https://doi.org/10.1007/s12020-023-03339-1CrossRefPubMedPubMedCentral

Biagetti B, Aulinas A, Casteras A, Pérez-Hoyos S, Simó R (2021) HOMA-IR in acromegaly: a systematic review and meta-analysis. Pituitary 24:146–158. https://doi.org/10.1007/s11102-020-01092-6CrossRefPubMed

10.

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 (2003) Glucose homeostasis in acromegaly: effects of long-acting somatostatin analogues treatment. Clin Endocrinol (Oxf) 59:492–499. https://doi.org/10.1046/j.1365-2265.2003.01876.xCrossRefPubMed

11.

Battezzati A, Benedini S, Fattorini A, Losa M, Mortini P, Bertoli S, Lanzi R, Testolin G, Biolo G, Luzi L (2003) Insulin action on protein metabolism in acromegalic patients. Am J Physiol Endocrinol Metab 284:E823–E829. https://doi.org/10.1152/ajpendo.00020.2002CrossRefPubMed

12.

Moller N, Schmitz O, Joorgensen JO, Astrup J, Bak JF, Christensen SE, Alberti KG, Weeke J (1992) Basal- and insulin-stimulated substrate metabolism in patients with active acromegaly before and after adenomectomy. J Clin Endocrinol Metab 74:1012–1019PubMed

13.

Alexopoulou O, Bex M, Kamenicky P, Mvoula AB, Chanson P, Maiter D (2014) Prevalence and risk factors of impaired glucose tolerance and diabetes mellitus at diagnosis of acromegaly: a study in 148 patients. Pituitary 17:81–89. https://doi.org/10.1007/s11102-013-0471-7CrossRefPubMed

14.

Wang Z, Gao L, Guo X, Feng C, Deng K, Lian W, Feng M, Bao X, Xing B (2019) Preoperative fasting C-Peptide acts as a promising predictor of improved glucose tolerance in patients with Acromegaly after Transsphenoidal surgery: a retrospective study of 64 cases from a large Pituitary Center in China. Front Endocrinol (Lausanne) 10:736. https://doi.org/10.3389/fendo.2019.00736CrossRefPubMed

15.

Shekhawat VS, Bhansali S, Dutta P, Mukherjee KK, Vaiphei K, Kochhar R, Sinha SK, Sachdeva N, Kurpad AV, Bhat K, Mudaliar S, Bhansali A (2019) Glucose-dependent Insulinotropic polypeptide (GIP) resistance and β-cell dysfunction contribute to Hyperglycaemia in Acromegaly. Sci Rep 9:5646. https://doi.org/10.1038/s41598-019-41887-7CrossRefPubMedPubMedCentral

16.

Niculescu D, Purice M, Lichiardopol R, Coculescu M (2010) Both insulin resistance and insulin secretion are involved in the pre-diabetes of Acromegaly. Acta Endocrinol 6:35–42. https://doi.org/10.4183/aeb.2010.35CrossRef

17.

Kinoshita Y, Fujii H, Takeshita A, Taguchi M, Miyakawa M, Oyama K, Yamada S, Takeuchi Y (2011) Impaired glucose metabolism in Japanese patients with acromegaly is restored after successful pituitary surgery if pancreatic {beta}-cell function is preserved. Eur J Endocrinol 164:467–473. https://doi.org/10.1530/EJE-10-1096CrossRefPubMed

18.

He W, Yan L, Wang M, Li Q, He M, Ma Z, Ye Z, Zhang Q, Zhang Y, Qiao N, Lu Y, Ye H, Lu B, Shou X, Zhao Y, Li Y, Li S, Zhang Z, Shen M, Wang Y (2019) Surgical outcomes and predictors of glucose metabolism alterations for growth hormone-secreting pituitary adenomas: a hospital-based study of 151 cases. Endocrine 63:27–35. https://doi.org/10.1007/s12020-018-1745-7CrossRefPubMed

19.

Niculescu DA, Dusceac R, Caragheorgheopol A, Popescu N, Poiana C (2019) Disposition Index in active acromegaly. Front Endocrinol (Lausanne) 10:637. https://doi.org/10.3389/fendo.2019.00637CrossRefPubMed

20.

Giustina A, Biermasz N, Casanueva FF, Fleseriu M, Mortini P, Strasburger C, van der Lely AJ, Wass J, Melmed S (2023) Consensus on criteria for acromegaly diagnosis and remission. https://doi.org/10.1007/s11102-023-01360-1. Acromegaly Consensus GroupPituitary

21.

ElSayed NA, Aleppo G, Aroda VR, Bannuru RR, Brown FM, Bruemmer D, Collins BS, Hilliard ME, Isaacs D, Johnson EL, Kahan S, Khunti K, Leon J, Lyons SK, Perry M, Lou, Prahalad P, Pratley RE, Seley JJ, Stanton RC, Gabbay RA, on behalf of the American Diabetes Association (2023) 2. Classification and diagnosis of diabetes: standards of Care in Diabetes-2023. Diabetes Care 46:S19–S40. https://doi.org/10.2337/dc23-S002CrossRefPubMed

22.

Cersosimo E, Solis-Herrera C, Trautmann ME, Malloy J, Triplitt CL (2014) Assessment of pancreatic β-cell function: review of methods and clinical applications. Curr Diabetes Rev 10:2–42CrossRefPubMedPubMedCentral

23.

Bunt JC, Krakoff J, Ortega E, Knowler WC, Bogardus C (2007) Acute insulin response is an independent predictor of type 2 diabetes mellitus in individuals with both normal fasting and 2-h plasma glucose concentrations. Diabetes Metab Res Rev 23:304–310. https://doi.org/10.1002/dmrr.686CrossRefPubMedPubMedCentral

24.

Gastaldelli A (2022) Measuring and estimating insulin resistance in clinical and research settings. Obesity 30:1549–1563. https://doi.org/10.1002/oby.23503CrossRefPubMed

25.

Espinosa-de-Los-Monteros AL, Gonzalez B, Vargas G, Sosa E, Mercado M (2011) Clinical and biochemical characteristics of acromegalic patients with different abnormalities in glucose metabolism. Pituitary 14:231–235CrossRefPubMed

26.

Ciresi A, Amato MC, Pivonello R, Nazzari E, Grasso LF, Minuto F, Ferone D, Colao A, Giordano C (2013) The metabolic profile in active acromegaly is gender-specific. J Clin Endocrinol Metab 98:E51–E59. https://doi.org/10.1210/jc.2012-2896CrossRefPubMed

27.

Niculescu D, Purice M, Coculescu M (2013) Insulin-like growth factor-I correlates more closely than growth hormone with insulin resistance and glucose intolerance in patients with acromegaly. Pituitary 16:168–174. https://doi.org/10.1007/s11102-012-0396-6CrossRefPubMed

28.

Petrossians P, Daly AF, Natchev E, Maione L, Blijdorp K, Sahnoun-Fathallah M, Auriemma R, Diallo AM, Hulting AL, Ferone D, Hana V, Filipponi S, Sievers C, Nogueira C, Fajardo-Montañana C, Carvalho D, Hana V, Stalla GK, Jaffrain-Réa ML, Delemer B, Colao A, Brue T, Neggers SJCMM, Zacharieva S, Chanson P, Beckers A (2017) Acromegaly at diagnosis in 3173 patients from the Liège Acromegaly Survey (LAS) database. Endocr Relat Cancer 24:505–518. https://doi.org/10.1530/ERC-17-0253CrossRefPubMedPubMedCentral

29.

Arosio M, Reimondo G, Malchiodi E, Berchialla P, Borraccino A, De Marinis L, Pivonello R, Grottoli S, Losa M, Cannavò 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, Italian Study Group of Acromegaly (2012) Predictors of morbidity and mortality in acromegaly: an Italian survey. Eur J Endocrinol 167:189–198. https://doi.org/10.1530/EJE-12-0084CrossRefPubMed

30.

Mestron A, Webb SM, Astorga R, Benito P, Catala M, Gaztambide S, Gomez JM, Halperin I, Lucas-Morante T, Moreno B, Obiols G, de Pablos P, Paramo C, Pico A, Torres E, Varela C, Vazquez JA, Zamora J, Albareda M, Gilabert M (2004) Epidemiology, clinical characteristics, outcome, morbidity and mortality in acromegaly based on the Spanish Acromegaly Registry (Registro Espanol De Acromegalia, REA). Eur J Endocrinol 151:439–446CrossRefPubMed

31.

Wolf P, Dormoy A, Maione L, Salenave S, Young J, Kamenický P, Chanson P (2022) Impairment in insulin secretion without changes in insulin resistance explains hyperglycemia in patients with acromegaly treated with pasireotide LAR. Endocr Connect 11:e220296. https://doi.org/10.1530/EC-22-0296CrossRefPubMedPubMedCentral

32.

Freda PU, Shen W, Reyes-Vidal CM, Geer EB, Arias-Mendoza F, Gallagher D, Heymsfield SB (2009) Skeletal muscle mass in acromegaly assessed by magnetic resonance imaging and dual-photon x-ray absorptiometry. J Clin Endocrinol Metab 94:2880–2886. https://doi.org/10.1210/jc.2009-0026CrossRefPubMedPubMedCentral

33.

Ferraù F, Albani A, Ciresi A, Giordano C, Cannavò S (2018) Diabetes secondary to Acromegaly: Physiopathology, clinical features and effects of Treatment. Front Endocrinol (Lausanne) 9:358. https://doi.org/10.3389/fendo.2018.00358CrossRefPubMed

34.

Hauguel-Moreau M, Hergault H, Cazabat L, Pépin M, Beauchet A, Aïdan V, Ouadahi M, Josseran L, Hage M, Rodon C, Dubourg O, Massy Z, Mansencal N (2023) Prevalence of prediabetes and undiagnosed diabetes in a large urban middle-aged population: the CARVAR 92 cohort. Cardiovasc Diabetol 22:31. https://doi.org/10.1186/s12933-023-01761-3CrossRefPubMedPubMedCentral

35.

Moody A, Cowley G, Ng Fat L, Mindell JS (2016) Social inequalities in prevalence of diagnosed and undiagnosed diabetes and impaired glucose regulation in participants in the health surveys for England series. BMJ Open 6:e010155. https://doi.org/10.1136/bmjopen-2015-010155CrossRefPubMedPubMedCentral

36.

Bjarkø VV, Haug EB, Sørgjerd EP, Stene LC, Ruiz PL, Birkeland KI, Berg TJ, Gulseth HL, Iversen MM, Langhammer A, Åsvold BO (2022) Undiagnosed diabetes: prevalence and cardiovascular risk profile in a population-based study of 52,856 individuals. The HUNT study, Norway. Diabet Med 39:e14829. https://doi.org/10.1111/dme.14829CrossRefPubMedPubMedCentral

37.

Yu H, Ho M, Liu X, Yang J, Chau PH, Fong DYT (2023) Incidence and temporal trends in type 2 diabetes by weight status: a systematic review and meta-analysis of prospective cohort studies. J Glob Health 13:04088. https://doi.org/10.7189/jogh.13.04088CrossRefPubMedPubMedCentral

38.

Yu H, Ho M, Liu X, Yang J, Chau PH, Fong DYT (2022) Association of weight status and the risks of diabetes in adults: a systematic review and meta-analysis of prospective cohort studies. Int J Obes 46:1101–1113. https://doi.org/10.1038/s41366-022-01096-1CrossRef

39.

Wang S, Wu J, Wang N, Zeng L, Wu Y (2017) The role of growth hormone receptor in β cell function. Growth Horm IGF Res 36:30–35. https://doi.org/10.1016/j.ghir.2017.08.002CrossRefPubMed

Titel: Glucose intolerance in acromegaly is driven by low insulin secretion; results from an intravenous glucose tolerance test
verfasst von: Laura Georgiana Zaifu
Dan Alexandru Niculescu
Andreea Elena Kremer
Andra Caragheorgheopol
Mariana Sava
Carmen Nicoleta Iordachescu
Roxana Dusceac
Iulia Florentina Burcea
Catalina Poiana
Publikationsdatum: 21.02.2024
Verlag: Springer US
Erschienen in: Pituitary / Ausgabe 2/2024
Print ISSN: 1386-341X
Elektronische ISSN: 1573-7403
DOI: https://doi.org/10.1007/s11102-024-01386-z

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