Editorial
Acromegaly: Diabetes and HOMA-IR
Diabetes y HOMA-IR en la acromegalia
a Servicio de Endocrinología y Nutrición, Hospital Universitario Vall d’Hebron, Universidad Autónoma de Barcelona, Grupo de investigación en Diabetes, Endocrinología y Metabolismo, Instituto de Investigación Vall d’Hebron (VHIR)
b Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
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array:4 [ "autoresLista" => "Betina Biagetti, Rafael Simó" "autores" => array:2 [ 0 => array:4 [ "nombre" => "Betina" "apellidos" => "Biagetti" "email" => array:2 [ 0 => "bbiagetti@hotmail.es" 1 => "bbiagetti@vhebron.net" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "Rafael" "apellidos" => "Simó" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Servicio de Endocrinología y Nutrición, Hospital Universitario Vall d’Hebron, Universidad Autónoma de Barcelona, Grupo de investigación en Diabetes, Endocrinología y Metabolismo, Instituto de Investigación Vall d’Hebron (VHIR)" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III (ISCIII), Madrid, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Diabetes y HOMA-IR en la acromegalia" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">The Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) is classically considered to be a good insulin resistance (IR) index in acromegaly (ACRO).<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> However, recent studies have provided data against the long assumed classical concept that insulin resistance is the main reason for the high prevalence of type 2 diabetes mellitus (DM2) in patients with ACRO.<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,3</span></a> In addition, the underlying pathophysiological mechanisms contributing to altered glucose metabolism in ACROs are not fully understood, and may be different from those traditionally implicated in DM2.<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4,5</span></a> On the other hand, insulin-like growth factor type I (IGF-1) is more closely correlated to glucose abnormalities than growth hormone (GH) measured randomly or after a glucose overload.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> Thus, although DM2 is a well-recognized comorbidity in ACRO, it remains subject to debate whether or not IR is the main underlying mechanism.</p><p id="par0010" class="elsevierStylePara elsevierViewall">HOMA-IR is a surrogate marker of IR based on the relationship between fasting glucose and insulin levels proposed by Matthews in 1985,<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> the formula being expressed as follows depending on the units in which glucose is expressed: <elsevierMultimedia ident="eq0005"></elsevierMultimedia><elsevierMultimedia ident="eq0010"></elsevierMultimedia></p><p id="par0015" class="elsevierStylePara elsevierViewall">Its use in ACRO is widespread, though there are certain aspects inherent to this disease condition that should be considered when interpreting HOMA-IR:<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">(1)</span><p id="par0020" class="elsevierStylePara elsevierViewall">In patients with ACRO, the HOMA-IR values could lead to falsely elevated results due to the cross-reactivity between IGF-1 and endogenous insulin observed in some of the currently available kits for measuring circulating insulin.</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">(2)</span><p id="par0025" class="elsevierStylePara elsevierViewall">It is not easy to determine whether a patient with ACRO has diabetes as a result of acromegaly or presented previous diabetes.</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">(3)</span><p id="par0030" class="elsevierStylePara elsevierViewall">Somatostatin analogs (SSAs) widely used in the treatment of ACRO can bind to somatostatin receptor subtypes 2 and 5 of the pancreatic beta cell, inhibiting insulin secretion,<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> and thus invalidating the use of the Matthews formula in this context.</p></li></ul></p><p id="par0035" class="elsevierStylePara elsevierViewall">The prevalence of DM2 in ACRO differs significantly among studies, ranging from 19 to 56%.<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4,8,9</span></a> This prevalence is not only higher than that of the general population, but is also higher than that of population groups at high risk of developing diabetes.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> Although this classically has been attributed to the diabetogenic action of growth hormone (GH), other possible implicated factors should be considered.</p><p id="par0040" class="elsevierStylePara elsevierViewall">Potential diagnostic bias is one such factor, since most patients undergo an oral glucose tolerance test during the ACRO diagnostic procedure. In addition, factors other than those traditionally involved in the development of DM2, such as the ectopic presence and dysfunction of visceral adipose tissue and alterations to certain adipokines,<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> as well as increased gluconeogenesis, could contribute to glycemic worsening in these patients.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,5,11</span></a> In this regard, our group found a reduction in branched-chain amino acid levels in 30 patients with active ACRO as compared to age-matched controls, consistent with activation of this gluconeogenic pathway.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> In addition, an increased prevalence of diabetes was reported during the follow-up of these patients,<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> probably reflecting the influence of other confounding factors such as age, specific treatment of acromegaly, and/or beta-cell deterioration.<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3,14</span></a> Overall, other factors in addition to GH appear to play a significant role in explaining the high prevalence of diabetes in patients with ACRO.</p><p id="par0045" class="elsevierStylePara elsevierViewall">In order to clarify the significance of HOMA-IR in patients with ACRO, we conducted a meta-analysis assessing HOMA-IR in patients with ACRO with and without diabetes as compared to their reference population.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> The results of this meta-analysis showed that HOMA-IR in previously untreated patients with active ACRO was higher than in the reference population, even in patients without diabetes. This finding confirms that insulin resistance is an early event in ACRO. In addition, the metabolic impact was different after surgery than it was when SSAs were used. Thus, although a decrease in HOMA-IR was seen with both treatments, it proved more effective with surgery at the expense of post-treatment improvement in basal glucose, which was not seen after SSA administration. This finding deserves specific comment, because the reduction in insulin levels induced by SSAs led to lower HOMA-IR values, which did not imply parallel reductions in insulin resistance. In fact, these patients had higher basal blood glucose levels associated with lower insulin levels. These findings suggest that HOMA-IR is not useful as a measure of insulin resistance in patients treated with SSAs.</p><p id="par0050" class="elsevierStylePara elsevierViewall">In sum, in patients with active ACRO without medical treatment, there is an increase in IR as assessed by HOMA versus the reference population, even in patients without diabetes. However, HOMA-IR is not a good method for assessing IR in ACRO patients treated with SSAs.</p><p id="par0055" class="elsevierStylePara elsevierViewall">Lastly, stricter monitoring of glucose levels in patients treated with SSAs seems advisable.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Biagetti B, Simó R. Diabetes y HOMA-IR en la acromegalia. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 4 | 1 | 5 |
| 2024 October | 42 | 13 | 55 |
| 2024 September | 28 | 16 | 44 |
| 2024 August | 28 | 15 | 43 |
| 2024 July | 28 | 9 | 37 |
| 2024 June | 23 | 7 | 30 |
| 2024 May | 17 | 10 | 27 |
| 2024 April | 20 | 4 | 24 |
| 2024 March | 20 | 9 | 29 |
| 2024 February | 19 | 4 | 23 |
| 2024 January | 28 | 3 | 31 |
| 2023 December | 16 | 4 | 20 |
| 2023 November | 33 | 6 | 39 |
| 2023 October | 30 | 6 | 36 |
| 2023 September | 26 | 1 | 27 |
| 2023 August | 20 | 2 | 22 |
| 2023 July | 18 | 6 | 24 |
| 2023 June | 24 | 7 | 31 |
| 2023 May | 34 | 7 | 41 |
| 2023 April | 33 | 3 | 36 |
| 2023 March | 16 | 2 | 18 |
| 2023 February | 29 | 1 | 30 |
| 2023 January | 54 | 8 | 62 |
| 2022 December | 21 | 7 | 28 |
| 2022 November | 9 | 4 | 13 |
| 2022 October | 14 | 7 | 21 |
| 2022 September | 16 | 8 | 24 |
| 2022 August | 19 | 12 | 31 |
| 2022 July | 16 | 10 | 26 |
| 2022 June | 10 | 9 | 19 |
| 2022 May | 12 | 10 | 22 |
| 2022 April | 7 | 7 | 14 |
| 2022 March | 20 | 9 | 29 |
| 2022 February | 14 | 10 | 24 |
| 2022 January | 31 | 4 | 35 |
| 2021 December | 30 | 12 | 42 |
| 2021 November | 35 | 10 | 45 |
| 2021 October | 45 | 10 | 55 |
| 2021 September | 28 | 6 | 34 |
| 2021 August | 41 | 1 | 42 |
| 2021 July | 18 | 11 | 29 |
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