HOMA-IR in acromegaly: a systematic review and meta-analysis

Biagetti, Betina; Aulinas, Anna; Casteràs, Anna; Pérez‐Hoyos, S.; Simó, Rafael

doi:10.1007/s11102-020-01092-6

Cited by 16 publications

(11 citation statements)

References 94 publications

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“…Up to half of patients have impaired glucose tolerance and diabetes mellitus ( 366 ) due to GH-mediated insulin resistance and long-term decreased pancreatic insulin reserve ( 367 ). Diabetes mellitus increases cardiovascular mortality ( 368 ) and influences the choice of medical therapy, with pegvisomant generally preferred to the SRL pasireotide due to a greater risk for hyperglycemia with use of pasireotide ( 369 ).…”

Section: Long-term Comorbidities and Mortality Outcomesmentioning

confidence: 99%

Clinical Biology of the Pituitary Adenoma

et al. 2022

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All endocrine glands are susceptible to neoplastic growth, yet the health consequences of these neoplasms differ between endocrine tissues. Pituitary neoplasms are highly prevalent and overwhelmingly benign, exhibiting a spectrum of diverse behaviors and impact on health. To understand the clinical biology of these common yet often innocuous neoplasms, we review pituitary physiology, and adenoma epidemiology, pathophysiology, behavior, and clinical consequences. The anterior pituitary develops in response to a range of complex brain signals integrating with intrinsic ectodermal cell transcriptional events that together determine gland growth, cell type differentiation, and hormonal production, in turn maintaining optimal endocrine health. Pituitary adenomas occur in ten percent of the population; however, the overwhelming majority remain harmless during life. Triggered by somatic or germline mutations, disease-causing adenomas manifest pathogenic mechanisms that disrupt intra-pituitary signaling to promote benign cell proliferation associated with chromosomal instability. Cellular senescence acts as a mechanistic buffer protecting against malignant transformation, an extremely rare event. It is estimated that fewer than one thousandth of all pituitary adenomas cause clinically significant disease. Adenomas variably and adversely affect morbidity and mortality depending on cell type, hormone secretory activity, and growth behavior. For most clinically apparent adenomas, multimodal therapy controlling hormone secretion and adenoma growth lead to improved quality of life and normalized mortality. The clinical biology of pituitary adenomas and particularly their benign nature stands in marked contrast to other tumors of the endocrine system such as thyroid and neuroendocrine tumors.

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Section: Long-term Comorbidities and Mortality Outcomesmentioning

confidence: 99%

Clinical Biology of the Pituitary Adenoma

et al. 2022

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“…Acromegaly is a state of insulin resistance. According to a recent, large metanalysis (492 patients with acromegaly vs. 12,745 population group), homeostasis model assessment for insulin resistance (HOMA-IR) in treatment-naïve patients is higher than in the reference population [ 33 ]. Consistently, cohort studies demonstrate decreased insulin sensitivity (Si) during intravenous glucose tolerance test [ 34 ], decreased glucose infusion rate during hyperinsulinemic euglycemic clamp [ 35 ], and decreased homeostasis model assessment for insulin sensitivity [ 5 ].…”

Section: Insulin Sensitivitymentioning

confidence: 99%

“…Consistently, cohort studies demonstrate decreased insulin sensitivity (Si) during intravenous glucose tolerance test [ 34 ], decreased glucose infusion rate during hyperinsulinemic euglycemic clamp [ 35 ], and decreased homeostasis model assessment for insulin sensitivity [ 5 ]. These insulin sensitivity indices are impaired not only in patients with secondary DM but also in patients with NGT [ 5 , 33 , 34 , 36 ], suggesting that insulin resistance is the primary pathophysiologic defect of glucose metabolism in acromegaly.…”

Section: Insulin Sensitivitymentioning

confidence: 99%

“…Insulin resistance is amenable upon successful acromegaly treatment, shown by significant improvements in the above markers post-surgery [ 33 , 35 , 36 ]. Interestingly, HOMA-IR decreases as early as 9 days postoperatively [ 36 ], reflecting exclusively the previous effect of acromegaly in insulin sensitivity.…”

Section: Insulin Sensitivitymentioning

confidence: 99%

“…Considering its secondary nature, the most effective treatment of DM is remission of acromegaly itself. Indeed, surgical treatment results into diabetes remission [ 10 ], improvement of glycemic status [ 7 ] and insulin sensitivity [ 33 , 35 , 36 ]. However, surgical remission cannot be achieved in 50% of cases [ 2 ] and medical therapy or radiotherapy may be needed.…”

Section: Treatment Of Secondary and Pasi-induced Dm In Acromegalymentioning

confidence: 99%

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Secondary diabetes mellitus in acromegaly

et al. 2023

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Secondary diabetes mellitus (DM) is a common complication of acromegaly, encountered in up to 55% of cases. Vice versa, the prevalence of acromegaly is markedly higher in cohorts of patients with type 2 DM (T2DM). The presence of secondary DM depends primarily on acromegaly status and is associated with increased cardiovascular morbidity, malignancy rate and overall mortality. The principal pathophysiologic mechanism is increased insulin resistance due to excessive lipolysis and altered fat distribution, reflected at the presence of intermuscular fat and attenuated, dysfunctional adipose tissue. Insulin resistance is ascribed to the direct, diabetogenic effects of growth hormone (GH), which prevail over the insulin-sensitizing effects of insulin-like growth factor 1 (IGF-1), probably due to higher glucometabolic potency of GH, IGF-1 resistance, or both. Inversely, GH and IGF-1 act synergistically in increasing insulin secretion. Hyperinsulinemia in portal vein leads to enhanced responsiveness of liver GH receptors and IGF-1 production, pointing towards a mutually amplifying loop between GH-IGF-1 axis and insulin. Secondary DM occurs upon beta cell exhaustion, principally due to gluco-lipo-toxicity. Somatostatin analogues inhibit insulin secretion; especially pasireotide (PASI) impairs glycaemic profile in up to 75% of cases, establishing a separate pathophysiologic entity, PASI-induced DM. In contrast, pegvisomant and dopamine agonizts improve insulin sensitivity. In turn, metformin, pioglitazone and sodium-glucose transporters 2 inhibitors might be disease-modifying by counteracting hyperinsulinemia or acting pleiotropically. Large, prospective cohort studies are needed to validate the above notions and define optimal DM management in acromegaly.

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