Secondary diabetes mellitus in acromegaly

Moustaki, Melpomeni; Paschou, Stavroula Α.; Xekouki, Paraskevi; Kotsa, Kalliopi; Peppa, Μelpomeni; Ψαλτοπούλου, Θεοδώρα; Kalantaridou, Sophia Ν.; Vryonidou, Andromachi

doi:10.1007/s12020-023-03339-1

Cited by 16 publications

(10 citation statements)

References 152 publications

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“…It appears that their effect is actually marginal, as their use is associated with a transient reduction in insulin levels, without, however, significant effects on glycemic homeostasis [35]. On the other hand, pasireotide is a second-generation SSA known to significantly worsen glucose metabolism, with an average increase of about 0.4-0.5% in HbA1c levels [36,37]; anyway, no patients in our cohort were on treatment with such a drug.…”

Section: Discussionmentioning

confidence: 79%

Effect of Cabergoline on weight and glucose metabolism in patients with acromegaly

Varaldo,

Prencipe,

Bona

et al. 2024

J Endocrinol Invest

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Purpose Cabergoline (CAB) has shown to have benefic effects on the metabolism in different clinical settings but its metabolic role in acromegaly disease has not been studied yet. Aim of our study was to evaluate the impact of CAB on glucose metabolism and weight in patients with acromegaly. Methods All patients with acromegaly undergoing continuous treatment with CAB for at least 6 months were retrospectively screened. Exclusion criteria were discontinuation of CAB for more than one month, change of antidiabetic or other therapy for acromegaly, concomitant untreated hormonal deficiency, initiation of pregnancy and/or breastfeeding. All patients were evaluated in terms of biochemical disease control, glucose metabolism and weight at baseline (T0) and after the introduction of CAB therapy at 6 (T6) and 12 months (T12). Results Twenty-six patients (15 females and 11 males) were evaluated at T0 and T6 and 19 patients (12 females and 7 males) were also evaluated at T12. Insulin-like growth factor I (IGF-I) and prolactin (PRL) levels were significantly lower at T6 and T12 compared to baseline (p < 0.001 for IGF-I, p < 0.05 for PRL) even if no further differences were observed between T12 and T6. Considering the entire cohort, no differences were appreciated regarding the metabolic parameters but a significant reduction in weight and body mass index (BMI) was observed at both T6 (p = 0.009 for weight, p = 0.021 for BMI) and T12 (p = 0.014 for weight, p = 0.017 for BMI) compared to baseline. Conclusion Our results confirm the efficacy of CAB in providing a significant improvement in the biochemical disease control but do not demonstrate a marked benefit on glucose metabolism of acromegaly patients. In such patients, CAB appears to have a rapid effect on weight and BMI, with significant changes noticeable as early as 6 months and persisting for at least 12 months.

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Section: Discussionmentioning

confidence: 79%

Effect of Cabergoline on weight and glucose metabolism in patients with acromegaly

Varaldo,

Prencipe,

Bona

et al. 2024

J Endocrinol Invest

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“…Помимо этого, ГР стимулирует глюконеогенез в печени и почках, а также гликогенолиз в печени и мышцах, снижает утилизацию глюкозы мышцами и нарушает профиль секреции адипокинов, что в совокупности также может приводить к гипергликемии [42]. Еще один важный фактор патогенеза СД при акромегалии -истощение островкового аппарата поджелудочной железы на фоне хронической гиперсекреции инсулина, которая отмечается как натощак, так и постпрандиально [35,43]. На экспериментальных животных моделях было показано, что введение ГР стимулирует быстрое высвобождение инсулина, приводит к усилению инсулинового ответа на гипергликемические и негипергликемические стимулы, индуцирует экспрессию и биосинтез генов инсулина, а также пролиферацию бета-клеток in vitro и ex vivo [43], то есть ГР характеризуется прямым стимулирующим действием на секрецию инсулина.…”

Section: патогенез нарушений углеводного обмена при акромегалииunclassified

“…Еще один важный фактор патогенеза СД при акромегалии -истощение островкового аппарата поджелудочной железы на фоне хронической гиперсекреции инсулина, которая отмечается как натощак, так и постпрандиально [35,43]. На экспериментальных животных моделях было показано, что введение ГР стимулирует быстрое высвобождение инсулина, приводит к усилению инсулинового ответа на гипергликемические и негипергликемические стимулы, индуцирует экспрессию и биосинтез генов инсулина, а также пролиферацию бета-клеток in vitro и ex vivo [43], то есть ГР характеризуется прямым стимулирующим действием на секрецию инсулина. Таким образом, диабетогенный потенциал ГР реализуется не только через механизмы инсулинорезистентности, но и через истощение бета-клеток островкового аппарата поджелудочной железы.…”

Section: патогенез нарушений углеводного обмена при акромегалииunclassified

“…В физиологических условиях ИРФ-1 увеличивает чувствительность к инсулину и его секрецию, а инсулин, в свою очередь, повышает количество рецепторов к ГР в печени и усиливает секрецию ИРФ-1 [43]. Инсулин и ИРФ-1 имеют структурное сходство, и рецепторы к ним являются членами одного подкласса трансмембранных тирозинкиназных рецепторов [47].…”

Section: патогенез нарушений углеводного обмена при акромегалииunclassified

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Diabetes mellitus in acromegaly: prevalence, pathophysiological particulars and treatment strategies

Ilovayskaya,

Galstyan

2023

Almanac of Clinical Medicine

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The prevalence of diabetes mellitus in acromegaly is significantly higher than that in the general population. Carbohydrate metabolism abnormalities often precede other phenotypic manifestations of acromegaly. The review presents data on the prevalence of carbohydrate metabolism disorders in acromegaly and describes their pathophysiological characteristics and approaches to treatment. Growth hormone (GH) excess is recognized as a key factor of glucose homeostasis abnormalities due to decreased insulin sensitivity (resulting from active lipolysis) and direct stimulation of insulin secretion. Insulin-like growth factor 1 (IGF1) improves insulin sensitivity; however, the GH diabetogenic effects prevail over the insulin-sensitizing impact of IGF1. Surgical and radiation treatment for somatotropinoma may indirectly improve carbohydrate metabolism, because they decrease the GH levels. Treatment with first generation somatostatin analogues can both improve glycemic control due to decreased GH levels and worsen it due to deterioration of postprandial insulin release, especially in patients with already manifest carbohydrate metabolism disorders. The GH receptor antagonist pegvisomant blocks the effects of excess GH on the target tissues without suppressing insulin secretion, which results in better glucose control; treatment with this agent can be preferred in patients with acromegaly and diabetes mellitus. Management of carbohydrate metabolism disorders in acromegaly is done in accordance with general treatment principles for type 2 diabetes mellitus.

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“…Acromegaly is characterised by three- to five-fold higher mortality than in the general population. An increased prevalence of some cardiovascular risk factors such as dyslipidemia, hypertension, obesity, impaired glucose tolerance, or diabetes mellitus secondary to acromegaly is typical for acromegaly [ 1 , 2 , 3 , 4 , 5 ]. The major causes of both morbidity and mortality in patients with acromegaly are cardiovascular diseases (CVDs), respiratory system diseases, and cancer.…”

Section: Introductionmentioning

confidence: 99%

FTO Gene Polymorphisms and Their Roles in Acromegaly

Jawiarczyk-Przybyłowska

Kuliczkowska-Płaksej

Kolačkov

et al. 2023

IJMS

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The major causes of both morbidity and mortality in patients with acromegaly are cardiovascular diseases (CVDs). The polymorphisms of the fat mass and obesity-associated gene (FTO) are associated with obesity, as well as with an increased risk of CVDs. The aim of the study was to determine the relationship of risk alleles of four FTO gene polymorphisms with selected parameters of lipid and glucose metabolism as well as with IGF-1 and GH levels in the group of patients with acromegaly compared to the control group. The study group consisted of 104 patients with acromegaly and 64 healthy subjects constituting the control group. In the whole acromegaly group, the data reveal that the homozygous for risk allele carriers (rs1421085, rs9930506, rs9939609) as well as carriers of only one risk allele have lower IGF-1 concentrations. In the well-controlled acromegaly group, the homozygous for three risk allele carriers of FTO gene polymorphisms have lower HDL cholesterol concentration (rs1121980, rs1421085, rs993609). In the cured acromegaly group, homozygous risk allele carriers rs9930506 tend to have higher levels of total cholesterol and LDL cholesterol. These associations are not observed in the control group. Conclusion: there is an association between FTO gene polymorphisms and the metabolism of lipids, suggesting that the FTO gene may be associated with higher CVD risk in patients with acromegaly. In addition, there is an association between FTO gene polymorphisms and IGF-1, implying that FTO gene may influence/modify IGF-1 synthesis. Further investigation on a larger scale is required to provide more precise evidence.

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Secondary diabetes mellitus in acromegaly

Cited by 16 publications

References 152 publications

Effect of Cabergoline on weight and glucose metabolism in patients with acromegaly

Effect of Cabergoline on weight and glucose metabolism in patients with acromegaly

Diabetes mellitus in acromegaly: prevalence, pathophysiological particulars and treatment strategies

FTO Gene Polymorphisms and Their Roles in Acromegaly

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