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Original article
Trabecular bone score and 25-hydroxyvitamin D levels in microvascular complications of type 2 diabetes mellitus
Índice trabecular óseo y niveles de 25-hidroxivitamina D en las complicaciones microvasculares de la diabetes mellitus tipo 2
Meryam Maamar el Asria, Emilio Pariente Rodrigoa,
Corresponding author
emilio.pariente@scsalud.es

Corresponding author.
, Sara Díaz-Salazar de la Flora, Stefanie Pini Valdiviesob, M. Carmen Ramos Barrónc, José M. Olmos Martínezd, José L. Hernández Hernándezd
a Centro de Salud Camargo-Interior, Universidad de Cantabria, Santander, Spain
b Servicio de Hospitalización Domiciliaria, Hospital Universitario Marqués de Valdecilla, Santander, Spain
c Centro de Salud Camargo-Costa, Universidad de Cantabria, Santander, Spain
d Servicio de Medicina Interna, Unidad de Metabolismo Óseo, Hospital Universitario Marqués de Valdecilla-IDIVAL, Universidad de Cantabria, Santander, Spain
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Diabetes mellitus &#40;DM&#41; is a major public health problem worldwide&#46; It is characterised by high plasma glucose levels and its nature often includes chronic complications that have a significant negative affect on the quality of life&#44; and add a high economic burden on patients and health systems<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a>&#46; Type 1 DM &#40;T1DM&#41; is associated with an autoimmune destruction of the pancreatic cells &#946;&#8239;leading to an absolute insulin deficiency&#46; Type 2 DM &#40;T2DM&#41;&#44; which accounts for more than 90&#37; of DM cases&#44; involves a functional deterioration of the cell&#8239;&#946;&#44; with a synergistic role being played by insulin resistance and inflammation&#46; The diabetic complications include microvascular diseases &#40;MVD&#41; &#8211; retinopathy&#44; nephropathy&#44; and neuropathy &#8211; and macrovascular disorders &#8211; ischemic heart disease &#40;IHD&#41;&#44; cerebrovascular disease &#40;CVD&#41;&#44; and peripheral arterial disease &#40;PAD&#41;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a>&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">Both types of diabetes have an increased risk of fracture&#46; T1DM is associated with an increased risk of hip fracture &#40;RR&#8239;&#61;&#8239;8&#46;9&#59; 95&#37; CI 7&#46;1&#8211;11&#46;2&#41;&#44; vertebral fracture &#40;VF&#41; and proximal humerus&#46; With respect to T2DM&#44; reports show an RR for hip fractures of 2&#46;7 &#40;95&#37; CI 1&#46;7&#8211;4&#46;4&#41; and an increased risk of VF in women &#40;OR&#8239;&#61;&#8239;1&#46;9&#59; 95&#37; CI 1&#46;1&#8211;3&#46;1&#41; and in men &#40;OR&#8239;&#61;&#8239;4&#46;7&#59; 95&#37; CI 2&#46;1&#8211;10&#46;2&#41;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a>&#46; In patients with T1DM the bone mineral density &#40;BMD&#41; is decreased&#44; while in those with T2DM it is often normal or even increased&#44; compared to non-diabetic subjects of the same age<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a>&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">The Trabecular Bone Score &#40;TBS&#41; is a parameter obtained from the bone densitometry image&#46; Two-dimensional densitometry images are transformed into three-dimensional structures using software installed on the densitometer itself&#44; and the score measures the texture of an image that correlates with the 3D determination of the trabecular structure&#46; This dimensionless score provides an indirect estimate of the trabecular architecture&#44; correlating well with the histomorphometric parameters&#44; and several studies have shown that low TBS values are associated with an increased risk of fracture due to fragility&#44; regardless of the BMD<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a>&#46; The TBS presents lower values in diabetic subjects than in non-diabetic subjects<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a>&#44; and it has proved useful in assessing the fracture risk in patients with T2DM<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a>&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Inflammation&#44; oxidative stress&#44; low bone turnover&#44; adipokine alterations&#44; WNT dysregulation&#44; and increased risk of falls related to sarcopenia or vitamin D deficiency are determinant factors of fracture risk in patients with T2DM<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a>&#46; It has also been suggested that MVD may be a key factor in skeletal disorders of the disease<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;3</span></a>&#44; suggesting that these microvascular alterations inside the diabetic bone could cause adverse changes in bone microstructure and&#44; consequently&#44; cause its quality to deteriorate<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a>&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">However&#44; other authors have not observed a specific relationship between MVD and bone fragility<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a>&#44; and from that perspective it has been argued that MVD would simply act as a marker of long-term DM or DM with poor metabolic control<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a>&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">There is an open debate on this issue<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a>&#44; with several aspects that have not yet been clarified&#46; One of them is the possible relationship between MVD and a decreased TBS&#44; on the assumption that MVD causes a deterioration in the trabecular microstructure which is an analysis to our knowledge that has not yet performed&#46; There is also controversy about the relationship between vitamin D deficiency and MVD<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8&#44;9</span></a>&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Based on the above&#44; we have proposed this study with the main objective of comparing the value of TBS in type 2 diabetic patients with and without MVD&#46; A secondary objective has been to determine the association between plasma levels of 25-hydroxyvitamin D &#40;25&#40;OH&#41;D&#41; and MVD&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Patients and methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Participants and study design</span><p id="par0040" class="elsevierStylePara elsevierViewall">A cross-sectional&#44; analytical observational study nested in a cohort was conducted&#46; The patients belong to a prospective population-based study&#44; the Camargo Cohort&#44; started in 2006 and set up to study bone metabolic diseases in the general population of our geographic area&#46; The cohort consists of males who are 50 years of age and older and postmenopausal females&#44; and their composition and design have been previously published<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a>&#46; At the baseline visit&#44; all patients were provided with a questionnaire on bone metabolism and general diseases&#44; current or past medication use&#44; and risk factors for osteoporosis and fractures&#46; They also underwent a laboratory study &#40;general and specific aimed at assessing bone metabolism&#41;&#44; a simple x-ray of the spine&#44; a bone densitometry &#40;DXA&#41; and a calcaneal ultrasonography&#46; After receiving information about the purpose of the cohort study&#44; the subjects were invited to participate&#44; and all participants gave their informed written consent&#46; The Camargo Cohort study was approved by the Cantabria Clinical Research Ethics Committee &#40;Internal Code&#58; 2016&#46;003&#41;&#46; The Declaration of Helsinki postulates for human research studies were followed&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">The study inclusion criteria were a previous diagnosis of T2DM and an initial assessment that ruled out the presence of diseases or treatments with an effect on bone metabolism&#44; such as primary hyperparathyroidism&#44; hyperthyroidism or the consumption of bisphosphonates&#44; estrogens&#44; raloxifene&#44; strontium ranelate&#44; teriparatide&#44; <span class="elsevierStyleSmallCaps">l</span>-thyroxine&#44; anticonvulsants or glucocorticoids&#44; in the year prior to inclusion&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Clinical variables</span><p id="par0050" class="elsevierStylePara elsevierViewall">Weight &#40;in kg&#41; and abdominal circumference &#40;in cm&#41; were logged&#46; Body mass index &#40;BMI&#41; was measured in kg&#47;m<span class="elsevierStyleSup">2</span>&#44; with obesity considered as BMI&#8239;&#62;&#8239;30&#8239;kg&#47;m<span class="elsevierStyleSup">2</span>&#46; Glomerular filtration &#40;GFR&#41;&#44; expressed in mL&#47;min&#47;1&#46;73&#8239;m<span class="elsevierStyleSup">2</span>&#44; was estimated according to the CKD-EPI formula<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a>&#46; Vertebral fracture &#40;VF&#41; was classified according to the grades of the Genant et al&#46; semiquantitative scale<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a>&#46; The diagnosis of macrovascular disease &#40;IHD&#44; CVD&#44; PAD&#41; was made according to the clinical history&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Microvascular disease &#40;MVD&#41;</span><p id="par0055" class="elsevierStylePara elsevierViewall">The definition of MVD was given due to the presence of nephropathy&#44; neuropathy and&#47;or retinopathy in a diabetic patient&#44; classed as nephropathy when albuminuria&#8239;&#8805;&#8239;30&#8239;mg&#47;g creatinine and&#47;or a sustained reduction in GFR estimated below 60&#8239;mL&#47;min&#47;1&#46;73&#8239;m<span class="elsevierStyleSup">2</span> for at least 3 months&#59; as neuropathy when a pathological monofilament test or the criterion of the American Diabetes Association of &#8220;the presence of symptoms and&#47;or signs of peripheral nerve dysfunction in a diabetic person in the absence of another diagnosis&#8221;&#59; and as retinopathy when confirmed by the ophthalmologist&#8217;s clinical diagnosis after an examination of the fundus<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;8</span></a>&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">The sample was classified into subjects without microvascular disease &#40;MVD&#8722;&#41; and subjects with microvascular disease &#40;MVD&#43;&#41;&#46; Additionally&#44; 4 subgroups were defined&#58; group A &#40;MVD- with macrovascular disease&#41;&#44; group B &#40;MVD- without macrovascular disease&#41;&#44; group C &#40;MVD&#43; with macrovascular disease&#41; and group D &#40;MVD&#8239;&#43;&#8239;without macrovascular disease&#41;&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Laboratory parameters</span><p id="par0065" class="elsevierStylePara elsevierViewall">Blood samples were obtained from a vein in the forearm in the early hours of the morning&#44; after a 12-h fast&#46; Concentrations of calcium&#44; phosphorus&#44; albumin&#44; total alkaline phosphatase &#40;tALP&#41;&#44; C-reactive protein &#40;CPR&#41;&#44; thyrotropin &#40;TSH&#41;&#44; total cholesterol&#44; high-density lipoprotein-bound cholesterol &#40;HDLc&#41;&#44; triglycerides and glycosylated hemoglobin &#40;HbA1c&#41; were obtained by an automated method &#40;ADVIA&#174; 2400 Chemistry System Autoanalyzer&#44; Siemens&#44; Germany&#41;&#46; Procollagen Type 1 N-terminal Propeptide &#40;P1NP&#41; and &#946;-C-terminal telopeptide of type 1 collagen &#40;&#946;-CTX&#41; were analysed as bone turnover markers &#40;BTMs&#41;&#46; The concentrations of 25&#40;OH&#41;D&#44; P1NP&#44; &#946;-CTX and intact parathyroid hormone &#40;iPTH&#41; were determined by an automated electrochemiluminescence method &#40;Elecsys&#174; 2010&#44; Roche Diagnostics&#44; GmbH&#44; Mannheim&#44; Germany&#41;&#46; The detection limits of iPTH&#44; P1NP and &#946;-CTX were 6&#8239;pg&#47;mL&#44; 5&#8239;ng&#47;mL and 0&#46;01&#8239;ng&#47;mL and the ranges of normality were 15&#8211;65&#8239;pg&#47;mL&#44; 15&#8722;78&#8239;ng&#47;mL and 0&#46;069&#8722;0&#46;760&#8239;ng&#47;mL&#44; respectively&#46; The 25&#40;OH&#41;D variable was analysed quantitatively&#46; Given the variations in vitamin D in relation to sunlight and the seasons<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a>&#44; the plasma level of 25&#40;OH&#41;D was analysed according to the month and season of the year in which the blood was taken&#46; The latitude of our geographical area &#40;Camargo&#44; Cantabria&#44; Spain&#41; is 43&#46;4086&#176; N&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Bone mineral density and TBS</span><p id="par0070" class="elsevierStylePara elsevierViewall">The BMD was assessed by DXA with the QDR-4500 machine by Hologic&#174; in 3 locations&#59; lumbar spine&#44; femoral neck and total hip&#46; In vivo precision was 0&#46;4&#8211;1&#46;5&#37; and the results were expressed in gr&#47;cm<span class="elsevierStyleSup">2</span>&#46; All measurements were performed by the same technician&#46; The TBS was obtained from lumbar spine DXA images &#40;L1-L4&#41; using specific software &#40;TBS iNsight&#174; v2&#46;1&#44; Medimaps&#44; M&#233;rignac&#44; France&#41; installed on the densitometer&#46; A degraded trabecular microstructure was considered as a TBS value&#8239;&#60;&#8239;1&#46;230&#44; partially degraded between 1&#46;230&#8722;1&#46;310&#44; and a normal TBS&#8239;&#62;&#8239;1&#46;310<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a>&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Statistical analysis</span><p id="par0075" class="elsevierStylePara elsevierViewall">Quantitative variables were expressed as mean &#40;standard deviation&#44; SD&#41; or median &#91;interquartile range&#93;&#44; as appropriate&#46; After checking the assumption of normality with the Kolmogorov-Smirnov test&#44; contrast tests were used such as the Student&#8217;s t-test&#44; ANOVA&#44; Kruskal-Wallis H or the Median test&#46; The Jonckheere-Terpstra test was used to calculate the <span class="elsevierStyleItalic">p-value</span> of trend&#46; The categorical variables were expressed as a percentage&#44; and the test was used for comparison &#967;<span class="elsevierStyleSup">2</span>&#46; Correlation analyses were performed using Pearson&#8217;s r or Spearman&#8217;s rho&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">In order to perform additional analyses&#44; the quantitative variables of age&#44; HbA1c and duration of the diabetes were transformed into dichotomous variables according to the median of the distributions&#46; The strength of an association was expressed with the <span class="elsevierStyleItalic">odds ratio</span> &#40;OR&#41; and its corresponding 95&#37; confidence interval &#40;95&#37; CI&#41;&#46; Two multivariate analyses &#40;logistic regression and general linear model&#41; were performed to discover the relationships between MVD and TBS&#44; adjusting for possible confounding variables&#46; A p-value of &#60;0&#46;05 was considered as significant&#46;</p></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Results</span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Sample description</span><p id="par0085" class="elsevierStylePara elsevierViewall">Of the 388 people with T2DM included in the Camargo Cohort&#44; 15 were ruled out for not meeting the inclusion criteria and 12 due to a lack of data &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; Finally&#44; 361 patients were analysed&#46; Of these&#44; 269 &#40;74&#46;5&#37;&#41; were MVD&#8722;&#44; distributed between group A &#40;n&#8239;&#61;&#8239;52&#41; and group B &#40;n&#8239;&#61;&#8239;217&#41;&#46; The remaining 92 &#40;25&#46;5&#37;&#41; were MVD&#43;&#44; distributed between group C &#40;n&#8239;&#61;&#8239;26&#41; and group D &#40;n&#8239;&#61;&#8239;66&#41;&#46; <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> summarises the general characteristics of the analysed sample&#46; The study-patients had a mean age of 63&#46;8 &#40;9&#46;7&#41; years&#44; an age range of 47&#8211;91 years&#44; an HbA1c of 7&#37;&#44; and an estimated GFR of 72&#8239;mL&#47;min&#47;1&#46;73&#8239;m<span class="elsevierStyleSup">2</span>&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0090" class="elsevierStylePara elsevierViewall">The MVD&#8239;&#43;&#8239;patients presented nephropathy &#40;n&#8239;&#61;&#8239;50&#41;&#44; neuropathy &#40;n&#8239;&#61;&#8239;15&#41;&#44; retinopathy &#40;n&#8239;&#61;&#8239;11&#41;&#44; or a combination of all three &#40;n&#8239;&#61;&#8239;16&#41;&#46; 78 patients were registered with macrovascular disease&#58; CI &#40;n&#8239;&#61;&#8239;25&#41;&#44; CVD &#40;n&#8239;&#61;&#8239;21&#41;&#44; PAD &#40;n&#8239;&#61;&#8239;13&#41; or a combination of these &#40;n&#8239;&#61;&#8239;18&#41;&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Bivariate analysis</span><p id="par0095" class="elsevierStylePara elsevierViewall">In the 361 diabetic patients&#44; HbA1c had significant inverse correlations with the TBS &#40;<span class="elsevierStyleItalic">r</span>&#8239;&#61;&#8239;&#8722;0&#46;17&#59; <span class="elsevierStyleItalic">p</span>&#8239;&#61;&#8239;0&#46;002&#41;&#44; with the BMD-LS &#40;<span class="elsevierStyleItalic">r</span>&#8239;&#61;&#8239;&#8722;0&#46;11&#59; <span class="elsevierStyleItalic">p</span>&#8239;&#61;&#8239;0&#46;049&#41;&#44; and with P1NP and &#946;-CTX &#40;<span class="elsevierStyleItalic">r</span>&#8239;&#61;&#8239;&#8722;0&#46;26&#59; <span class="elsevierStyleItalic">p</span>&#8239;&#61;&#8239;0&#46;0001 and <span class="elsevierStyleItalic">r</span>&#8239;&#61;&#8239;&#8722;0&#46;20&#59; <span class="elsevierStyleItalic">p</span>&#8239;&#61;&#8239;0&#46;0001&#44; respectively&#41;&#46; No significant associations were observed between HbA1c and 25&#40;OH&#41;D or BMD levels in the femoral neck or total hip&#46; The years of duration of diabetes and the TBS showed no correlation &#40;<span class="elsevierStyleItalic">r</span>&#8239;&#61;&#8239;0&#46;03&#59; <span class="elsevierStyleItalic">p</span>&#8239;&#61;&#8239;0&#46;47&#41;&#46; 25&#40;OH&#41;D levels were negatively correlated with iPTH &#40;<span class="elsevierStyleItalic">r</span>&#8239;&#61;&#8239;&#8722;0&#46;27&#59; <span class="elsevierStyleItalic">p</span>&#8239;&#61;&#8239;0&#46;0001&#41;&#44; and positively correlated with the TBS &#40;<span class="elsevierStyleItalic">r</span>&#8239;&#61;&#8239;0&#46;11&#59; <span class="elsevierStyleItalic">p</span>&#8239;&#61;&#8239;0&#46;03&#41;&#44; in a ratio that remained significant after adjusting for sex&#44; age&#44; iPTH levels&#44; BMI and season of the year&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">The MVD&#8239;&#43;&#8239;patients were older&#44; had poorer metabolic control&#44; increased insulin and oral antidiabetic use&#44; a lower plasma level of 25&#40;OH&#41;D&#44; and a lower TBS&#46; These characteristics were maintained when stratified by sex &#40;<a class="elsevierStyleCrossRefs" href="#tbl0005">Tables 1 and 2</a>&#41;&#46; The value of the BMD in the 3 locations and of the analysed BTMs&#44; P1NP and &#946;-CTX&#44; was similar in both groups&#44; and there were no significant differences in the prevalence and severity of VF &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0105" class="elsevierStylePara elsevierViewall">The group with isolated MVD &#40;Group D&#44; 68&#46;2 &#91;9&#46;6&#93; years&#41; presented the lowest TBS&#44; while the group with isolated macrovascular disease &#40;Group A&#44; 69&#46;7 &#91;9&#46;2&#93; years&#41; presented the highest TBS&#46; Between both of them&#44; the TBS values of the group without macrovascular or microvascular disease &#40;Group B&#44; 66&#46;1 &#91;8&#46;6&#93; years&#41; and of the group with both diseases &#40;Group C&#44; 71&#46;8 &#91;9&#46;3&#93; years&#41; were positioned&#46; &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46; The lowest TBS was observed in patients with retinopathy &#40;TBS&#8239;&#61;&#8239;1&#46;186 &#91;0&#46;2&#93;&#41;&#44; followed by nephropathy &#40;TBS&#8239;&#61;&#8239;1&#46;234 &#91;0&#46;2&#93;&#41; and neuropathy &#40;TBS&#8239;&#61;&#8239;1&#46;252 &#91;0&#46;2&#93;&#41;&#44; although the differences were not significant &#40;<span class="elsevierStyleItalic">p</span>&#8239;&#61;&#8239;0&#46;59&#41;&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0110" class="elsevierStylePara elsevierViewall">46&#46;2&#37; of the MVD&#8239;&#43;&#8239;patients and 30&#46;1&#37; of MVD&#8722; patients had a TBS&#8239;&#60;&#8239;1&#46;230&#44; while 36&#46;6&#37; of those with MVD&#43; and 47&#46;2&#37; of those with MVD&#8722; had TBS values &#62;1&#46;310 &#40;<span class="elsevierStyleItalic">p</span>&#8239;&#61;&#8239;0&#46;01&#41;&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">When the patients were classified simultaneously according to the HbA1c value and the duration of disease&#44; it was seen that the MVD&#43; patients had an elevated HbA1c accompanied by TBS&#8239;&#60;&#8239;1&#46;230&#44; regardless of the duration of the disease &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#41;&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0120" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#fig0020">Fig&#46; 4</a> shows the variations in 25&#40;OH&#41;D levels relative to the TBS&#46; MVD&#43; patients showed significantly lower values of 25&#40;OH&#41;D in the presence of a TBS corresponding to a degraded or partially degraded trabecular architecture&#44; while in the MVD- patients the values of 25&#40;OH&#41;D did not show any variation in relation with the TBS &#40;<a class="elsevierStyleCrossRef" href="#fig0020">Fig&#46; 4</a>&#41;&#46; The MVD was associated with a significant risk as it presented a plasma level of 25&#40;OH&#41;D&#8239;&#60;&#8239;20&#8239;ng&#47;mL&#44; with an OR&#8239;&#61;&#8239;1&#46;88 &#40;95&#37; CI 1&#46;06&#8211;3&#46;31&#59; p&#8239;&#61;&#8239;0&#46;028&#41;&#44; after adjusting for sex&#44; age&#44; BMI&#44; season of the year&#44; the GFR&#44; iPTH levels&#44; the TBS&#44; lumbar BMD and the presence of prevalent VF&#46;</p><elsevierMultimedia ident="fig0020"></elsevierMultimedia></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Multivariable models</span><p id="par0125" class="elsevierStylePara elsevierViewall">The mean value of TBS in patients with MVD&#43; was 1&#46;252 &#40;95&#37; CI 1&#46;230&#8722;1&#46;274&#41;&#44; compared with a value of 1&#46;281 &#40;95&#37; CI 1&#46;267&#8722;1&#46;295&#41; in those MVD&#8722; &#40;<span class="elsevierStyleItalic">p</span>&#8239;&#61;&#8239;0&#46;034&#41;&#44; after adjusting for sex&#44; age&#44; BMI&#44; MS&#44; tobacco and alcohol use&#44; insulin treatment&#44; OADs and statins&#44; GFR&#44; 25&#40;OH&#41;D levels&#44; iPTH&#44; P1NP and &#946;-CTX&#44; lumbar BMD&#44; HbA1c&#44; duration of diabetes and the presence of macrovascular disease&#46; Additionally&#44; MVD was associated with an increased risk of developing a TBS value &#60;1&#46;230&#44; with an OR&#8239;&#61;&#8239;2&#46;66 &#40;95&#37; CI 1&#46;18&#8211;6&#46;00&#59; <span class="elsevierStyleItalic">p</span>&#8239;&#61;&#8239;0&#46;018&#41;&#44; after adjusting for the same confounders as in the general linear model&#46; The ROC curve associated with the logistic regression model showed an area under the curve of 0&#46;898 &#40;95&#37; CI 0&#46;861&#8722;0&#46;934&#41;&#59; <span class="elsevierStyleItalic">p</span>&#8239;&#61;&#8239;0&#46;0001&#46;</p></span></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Discussion</span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Microvascular disease and TBS</span><p id="par0130" class="elsevierStylePara elsevierViewall">In this study conducted with patients with T2DM&#44; those with MVD&#43; had a significantly lower TBS than the MVD&#8722; patients&#44; after adjusting for the duration of the disease and the degree of metabolic control&#44; etc&#46; In contrast&#44; the BMD showed no significant differences between the two groups&#46; To our knowledge&#44; this is the first study to show a relationship between diabetic MVD and a low TBS&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">The different clinical manifestations of MVD were associated with the bone fragility of the DM&#46; Thus&#44; retinopathy was associated with a low BMD<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> and with an increased risk of incidental fracture<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a>&#46; In a prospective study of 3654 subjects &#62; 49 years old&#44; Ivers et al&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> observed&#44; after a two-year follow-up&#44; that diabetic retinopathy&#44; a duration of diabetes &#62; 10 years&#44; advanced cataracts and insulin treatment were significantly associated with an increased risk of fracture&#44; and suggested that retinopathy would act as a marker of advanced and severe diabetes&#46; Regarding nephropathy&#44; Vestergaard et al&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> studied 124&#44;655 cases of fracture and 373&#44;962 controls matched according to sex and age&#44; and observed that only nephropathy&#44; and not other complications of DM&#44; increased the risk of fracture in patients with T1DM and T2DM&#46; The authors suggested the possibility of an association of nephropathy with high blood glucose levels&#44; which could weaken bone strength&#46; In relation to neuropathy and the incidence of fracture&#44; proprioceptive impairment has been associated as a trigger to an increased risk of falls&#46; However&#44; other lines of research have recently been proposed&#44; such as the molecular and cellular link between neuropathy and the bone&#44; and the changes in blood microcirculation associated with this complication<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a>&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">There is an open debate about if MVD simply develops in parallel with diabetic bone disease due to similar pathophysiological mechanisms &#40;both are markers of long-term disease and poor glycemic control&#41;&#44; or if there is a specific causal relationship between the two entities<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a>&#46; There is evidence that changes in the bone structure in the diabetic patient may be partly related to poor perfusion&#44; so that microvascular complications would act as risk factors for bone deterioration in T1DM and T2DM<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a>&#46; In fact&#44; in line with previous studies<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a>&#44; recent studies in patients with MVD have shown a relationship between low transcutaneous oxygen pressure &#8211; as a microvascular blood flow measure &#8211; and an increase in cortical porosity &#8211; assessed by high-resolution peripheral quantitative computed tomography&#44; HR-pQCT &#8211; after adjusting for age&#44; sex and BMI<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a>&#46; Based on these observations&#44; it has been suggested that bone fragility could be part of an extended clinical spectrum of MVD<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a>&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">A proposed pathophysiological mechanism&#44; which would mediate between microvascular complications and bone fragility<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4&#44;5</span></a>&#44; are the advanced glycation end products &#40;AGEs&#41;&#46; AGEs are a heterogeneous group of molecules generated by the non-enzymatic reaction of proteins&#44; including type I collagen&#44; that increase in the bone matrix with age and hyperglycemia&#46; Through the nuclear factor &#954;-&#946;&#44; the AGEs increase oxidative stress and the expression of inflammatory mediators<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a>&#44; as well as the apoptosis of osteoblasts<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a> and reduce the bone material strength index measured by microindentation<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a>&#46; All of this occurs with adverse effects on the biomechanical properties of cortical and trabecular bone<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a>&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">The significant poor metabolic control presented by MVD&#43; patients in our study would facilitate the accumulation of AGEs&#44; which curiously appear to also accelerate atherosclerotic calcification in the bone microcirculation<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a>&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">The need for further studies to examine the values of bone parameters for different values of HbA1c and the different duration of diabetes is ongoing<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a>&#46; Both can influence the risk of fracture&#44; and act as confounder variables that must be considered<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a>&#46; Following this concept&#44; we have analysed both variables and we have not seen any relationship between the duration of diabetes and the TBS&#46; On the contrary&#44; we have observed a significant inverse correlation between HbA1c and the TBS&#46; In the same sense&#44; in people with MVD&#43;&#44; the impact of metabolic control on the TBS has been greater than that of the duration of diabetes&#58; in particular&#44; in MVD&#43; patients&#44; a high HbA1c was accompanied by a TBS in the range of degraded trabecular structure&#44; regardless of the duration of the disease &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#41;&#46; Both the duration of the diabetes and the value of HbA1c were included as adjustment variables in the multivariable models&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall">The effect of MVD on the bone was not been reflected in the BMD or plasma levels of P1NP and &#946;-CTX&#46; Published studies indicate that the DXA does not adequately characterise increased bone fragility in patients with T2DM and MVD<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a>&#46; Based on our results&#44; the MVD appears to affect another determinant of bone fragility&#44; independent of BMD&#44; such as the trabecular structure&#46; Regarding the BTMs&#44; the data published in the MVD are scarce and inconsistent<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a>&#46; However&#44; in the interpretation of the results it is worth noting the possible interference of the AGEs in the measurement of &#946;-CTX&#44; and the fact that the BTMs reflect the overall activity of the skeleton&#44; rather than a defect in the cellular activity of a particular compartment&#44; the cortical or trabecular bone&#46;</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Microvascular disease and plasma level of 25&#40;OH&#41;D</span><p id="par0165" class="elsevierStylePara elsevierViewall">According to our results&#44; a low level of 25&#40;OH&#41;D was associated with the prevalent MVD&#44; and in turn&#44; the MVD was associated with a significant risk of presenting 25&#40;OH&#41;D &#60;20&#8239;ng&#47;mL levels&#44; after adjusting for the confounding variables&#46;</p><p id="par0170" class="elsevierStylePara elsevierViewall">Vitamin D deficiency is currently considered a risk factor for cardiovascular disease&#44; and these patients present an increased risk for DM&#44; coronary heart disease&#44; and stroke&#44; as well as increased cardiovascular mortality<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a>&#46; In a previous study by the Camargo Cohort of 998 men &#62; 50 years of age from the general population&#44; it was observed that vitamin D deficiency was inversely related to abdominal aortic calcification &#40;AAC&#41;&#44; evaluated according to the 24-point scale&#46; Specifically&#44; as the plasma level of 25&#40;OH&#41;D descended &#40;&#62;30&#44; 20&#46;1&#8211;30&#44; 10&#46;1&#8211;20 and &#8804;10&#8239;ng&#47;mL&#41;&#44; increased values of AAC &#40;2&#46;7&#8239;&#177;&#8239;4&#46;9&#44; 3&#46;1&#8239;&#177;&#8239;4&#46;5&#44; 4&#8239;&#177;&#8239;0&#46;7 and 4&#46;4&#8239;&#177;&#8239;4&#46;1&#44; respectively&#59; <span class="elsevierStyleItalic">p</span>&#8239;&#61;&#8239;0&#46;03&#41;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a>&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">Also&#44; according to the publication&#44; there seems to be an association between vitamin D deficiency and microcirculation disorders&#44; such as cerebral small vessel disease&#44; retinopathy&#44; nephropathy&#44; peripheral neuropathy&#44; or coronary microcirculation disorders<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a>&#46; In the same way&#44; a longitudinal work&#44; based on data from the FIELD study<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a>&#44; showed that low plasma levels of 25&#40;OH&#41;D&#44; at 5 years of follow-up&#44; were predictors of MVD or macrovascular disease&#44; regardless of treatment and duration of diabetes&#46; Based on these observations&#44; the sequence &#8220;<span class="elsevierStyleItalic">vitamin D deficiency-microvascular disorders-cardiovascular disease</span>&#8221;&#44; with endothelial activation and inflammation as mediating factors&#44; has been put forward<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a>&#46;</p><p id="par0180" class="elsevierStylePara elsevierViewall">Additionally&#44; vitamin D deficiency has traditionally been considered to greatly affect the cortical bone<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a>&#59; however&#44; recent studies on the general population have linked vitamin D deficiency to an altered trabecular structure&#44; after adjusting for confounding variables<a class="elsevierStyleCrossRefs" href="#bib0145"><span class="elsevierStyleSup">29&#44;30</span></a>&#46; Although there is no strong evidence of an association between vitamin D deficiency and TBS in the general population<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a>&#44; in our study on the T2DM population a direct correlation was observed between 25&#40;OH&#41;D levels and TBS values &#40;<span class="elsevierStyleItalic">r</span>&#8239;&#61;&#8239;0&#46;11&#59; <span class="elsevierStyleItalic">p</span>&#8239;&#61;&#8239;0&#46;03&#41;&#44; which remained significant after adjusting for age&#44; sex&#44; BMI&#44; iPTH levels and the season of the year&#46;</p><p id="par0185" class="elsevierStylePara elsevierViewall">According to our results&#44; patients with MVD associated at least two adverse circumstances for bone trabecular structure&#58; a poor metabolic control &#8211; which facilitates the accumulation of AGEs<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;3</span></a> &#8211; and a low plasma level of 25&#40;OH&#41;D&#44; which based on the recent studies&#44; could contribute to the development of MVD<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a> and a reduction in the TBS<a class="elsevierStyleCrossRefs" href="#bib0145"><span class="elsevierStyleSup">29&#44;30</span></a>&#46;</p><p id="par0190" class="elsevierStylePara elsevierViewall">The study has some limitations that need to be considered&#46; First&#44; the cross-sectional design makes it possible to detect associations&#44; but not to establish causality&#46; The number of patients in the cohort who met inclusion criteria was relatively low&#44; with the added effect of successive stratification on statistical power and the risk of making a type II error&#46; Dietary intake of dairy products or calcium and&#47;or vitamin D supplements have not been analysed as possible confounding variables&#46; On the other hand&#44; we believe there are two points of interest&#46; To our knowledge&#44; it is the first study to demonstrate a relationship between diabetic MVD and impaired trabecular architecture as measured by the TBS&#46; Finally&#44; the analysed population belongs to a large prospective study&#44; the Camargo Cohort&#44; which has been an added advantage in terms of reliability and data quality&#46;</p></span></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Conclusions</span><p id="par0195" class="elsevierStylePara elsevierViewall">In this study&#44; performed on 361 type 2 diabetic patients belonging to the general population&#44; with an acceptable metabolic control and a low prevalence of VF&#44; MVD&#43; patients presented a significantly lower TBS than the MVD- patients&#44; after adjusting for the confounding variables&#46; There has also been a consistent and significant association between low plasma levels of 25&#40;OH&#41;D and the prevalent MVD&#46;</p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Conflict of interest</span><p id="par0200" class="elsevierStylePara elsevierViewall">The authors state that they have no conflicts of interest&#46;</p></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0150">Funding</span><p id="par0205" class="elsevierStylePara elsevierViewall">The study is funded in part by the <span class="elsevierStyleGrantSponsor" id="gs0005">Carlos III Health Institute</span> &#40;<span class="elsevierStyleGrantNumber" refid="gs0005">PI18&#47;00762</span>&#41;&#44; which includes ERDF funds from the EU &#40;Ministry of Economy and Competitiveness&#44; Spain&#41;&#46;</p></span></span>"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Background and objective</span><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Diabetic microvascular disease &#40;MVD&#41; has been associated with increased bone fragility&#46; The objective was to analyse the relationship between MVD and trabecular microstructure &#8211; assessed by the trabecular bone score &#40;TBS&#41; &#8211; in type 2 diabetic &#40;T2D&#41; patients&#46; A second aim was to know the relationship between vitamin D and MVD&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Patients and methods</span><p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Cross-sectional study&#44; which included men &#62;50 years and postmenopausal women participating in a population-based cohort&#44; diagnosed with T2D&#46; The presence of nephropathy&#44; neuropathy and&#47;or retinopathy was classified as MVD&#43;&#46; Clinical and laboratory variables&#44; TBS&#44; 25&#40;OH&#41;D and BMD by DXA&#44; were evaluated&#46; Bivariate and multivariate analysis were performed&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">We evaluated 361 patients &#40;51&#46;1&#37; women&#41;&#44; 63&#46;8 &#40;9&#41; years old&#46; Of them&#44; 92 were MVD&#43; and presented poorer metabolic control&#44; longer duration of T2D&#44; lower TBS &#91;1&#46;235 &#40;0&#46;1&#41; vs&#46; 1&#46;287 &#40;0&#46;1&#41;&#59; p&#8239;&#61;&#8239;0&#46;007&#93; and lower levels of 25&#40;OH&#41;D &#91;18&#46;3 &#40;7&#41; vs&#46; 21&#46;6 &#40;8&#41;&#8239;ng&#47;mL&#59; p&#8239;&#61;&#8239;0&#46;0001&#41;&#46; There were no differences between MVD&#43; and MVD&#8722; with regard to BMD or P1NP and &#946;-CTX markers&#46; After adjusting for confounders&#44; including HbA1c and duration of T2D&#44; the TBS value in MVD&#43; was 1&#46;252 &#40;95&#37; CI 1&#46;230&#8211;1&#46;274&#41; vs&#46; 1&#46;281 &#40;95&#37; CI 1&#46;267&#8211;1&#46;295&#41; in MVD&#8722; &#40;p&#8239;&#61;&#8239;0&#46;034&#41;&#46; MVD was associated with a 25&#40;OH&#41;D level &#60;20&#8239;ng&#8239;ml with an adjusted OR of 1&#46;88 &#40;95&#37; CI 1&#46;06&#8211;3&#46;31&#59; p&#8239;&#61;&#8239;0&#46;028&#41;&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">The MVD&#43; patients presented a significantly lower TBS&#44; after adjusting for confounders&#46; Furthermore&#44; multivariable analysis showed a significant relationship between a low 25&#40;OH&#41;D level and a prevalent MVD&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Background and objective"
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          1 => array:2 [
            "identificador" => "abst0010"
            "titulo" => "Patients and methods"
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          2 => array:2 [
            "identificador" => "abst0015"
            "titulo" => "Results"
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          3 => array:2 [
            "identificador" => "abst0020"
            "titulo" => "Conclusions"
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      "es" => array:3 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Antecedentes y objetivo</span><p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">La enfermedad microvascular &#40;EMV&#41; diab&#233;tica ha sido asociada con una fragilidad &#243;sea incrementada&#46; El objetivo fue analizar la relaci&#243;n entre la EMV y la microestructura trabecular &#8211; evaluada mediante el &#237;ndice trabecular &#243;seo &#40;trabecular bone score&#44; TBS&#41; &#8211; en pacientes diab&#233;ticos tipo 2 &#40;DM2&#41;&#46; Adicionalmente&#44; conocer la relaci&#243;n entre la vitamina D y la EMV&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Pacientes y m&#233;todos</span><p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">Dise&#241;o transversal anal&#237;tico&#44; que incluy&#243; varones &#62; 50 a&#241;os y mujeres postmenop&#225;usicas con DM2&#44; participantes en una cohorte poblacional&#46; Se clasific&#243; como EMV&#43; la presencia de nefropat&#237;a&#44; neuropat&#237;a y&#47;o retinopat&#237;a&#46; Fueron analizadas variables cl&#237;nicas&#44; de laboratorio&#44; el TBS&#44; la 25-hidroxivitamina D &#91;25&#40;OH&#41;D&#93; y la densidad mineral &#243;sea &#40;DMO&#41;&#46; Se realizaron an&#225;lisis bivariable y multivariable&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">Fueron evaluados 361 pacientes &#40;51&#44;1&#37; mujeres&#41;&#44; de 63&#44;8 &#40;9&#41; a&#241;os&#46; De ellos&#44; 92 ten&#237;an EMV&#44; con un peor control metab&#243;lico&#44; mayor duraci&#243;n de la DM2&#44; menor TBS &#40;1&#44;235 &#91;0&#44;1&#93; vs&#46; 1&#44;287 &#91;0&#44;1&#93;&#59; p&#8239;&#61;&#8239;0&#44;003&#41; y menores niveles de 25&#40;OH&#41;D &#40;18&#44;3 &#91;7&#93; vs&#46; 21&#44;6 &#91;8&#93;&#8239;ng&#47;mL&#59; p&#8239;&#61;&#8239;0&#44;0001&#41;&#46; No hubo diferencias entre EMV&#43; y EMV&#8722; en la DMO ni en los marcadores P1NP y &#946;-CTX&#46; Tras ajustar por confusores&#44; incluyendo HbA1c y duraci&#243;n de la DM2&#44; el TBS en EMV&#43; fue 1&#44;252 &#40;IC 95&#37; 1&#44;230&#8211;1&#44;274&#41; vs&#46; 1&#44;281 &#40;IC 95&#37; 1&#44;267&#8211;1&#44;295&#41; en EMV&#8722; &#40;p&#8239;&#61;&#8239;0&#44;034&#41;&#46; La EMV se asoci&#243; a un nivel de 25&#40;OH&#41;D&#8239;&#60;&#8239;20&#8239;ng&#47;mL con una OR ajustada&#8239;&#61;&#8239;1&#44;88 &#40;IC 95&#37; 1&#44;06&#8211;3&#44;31&#59; p&#8239;&#61;&#8239;0&#44;028&#41;&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0090" class="elsevierStyleSimplePara elsevierViewall">Los pacientes con EMV presentaron un TBS significativamente menor&#44; tras ajustar por confusores&#46; El an&#225;lisis multivariable mostr&#243; asimismo una asociaci&#243;n significativa entre un nivel bajo de 25&#40;OH&#41;D y la EMV prevalente&#46;</p></span>"
        "secciones" => array:4 [
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            "titulo" => "Pacientes y m&#233;todos"
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            "identificador" => "abst0035"
            "titulo" => "Resultados"
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          3 => array:2 [
            "identificador" => "abst0040"
            "titulo" => "Conclusiones"
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    "NotaPie" => array:1 [
      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Maamar el Asri M&#44; Pariente Rodrigo E&#44; D&#237;az-Salazar de la Flor S&#44; Pini Valdivieso S&#44; Ramos Barr&#243;n MC&#44; Olmos Mart&#237;nez JM&#44; et al&#46; &#205;ndice trabecular &#243;seo y niveles de 25-hidroxivitamina D en las complicaciones microvasculares de la diabetes mellitus tipo 2&#46; Med Clin &#40;Barc&#41;&#46; 2022&#59;158&#58;308&#8211;314&#46;</p>"
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          "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">TBS values in the patients of the sample&#44; classified according to the presence of microvascular and macrovascular disease&#46;</p>"
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          "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Plasma values of 25&#40;OH&#41;D in the study patients&#44; according to the TBS value and the presence of microvascular disease&#46;</p>"
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          "leyenda" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">MVD&#43;&#58; with microvascular disease&#59; MVD&#8722;&#58; without microvascular disease&#59; HbA1c&#58; glycosylated hemoglobin&#46;</p><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Quantitative variables&#44; expressed as mean &#40;SD&#41; or median &#40;interquartile range&#41;&#46;</p>"
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Total</th><th class="td" title="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Women</th><th class="td" title="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Men</th></tr><tr title="table-row"><th class="td" title="\n
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                  \t\t\t\t" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t" scope="col">MVD&#43;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col">MVD&#8722;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col"><span class="elsevierStyleItalic">p</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">MVD&#43;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">MVD-&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col"><span class="elsevierStyleItalic">p</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col">MVD&#43;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col">MVD&#8722;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col"><span class="elsevierStyleItalic">p</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&#40;n&#8239;&#61;&#8239;92&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&#40;n&#8239;&#61;&#8239;269&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t">Age <span class="elsevierStyleItalic">&#40;years&#41;</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">69&#46;3 &#40;9&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">66&#46;8 &#40;8&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#46;023&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">68&#46;8 &#40;10&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">66&#46;6 &#40;8&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;19&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Years of menopause&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">17&#46;8 &#40;10&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;026&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">21&#46;7 &#40;12&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">17&#46;8 &#40;10&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;024&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Abdominal circumference <span class="elsevierStyleItalic">&#40;cm&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">103&#46;8 &#40;11&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;013&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">106 &#40;14&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">103&#46;5 &#40;11&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;22&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">109&#46;9 &#40;10&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">104 &#40;10&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;003&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Body mass index <span class="elsevierStyleItalic">&#40;kg&#47;m</span><span class="elsevierStyleSup">2</span><span class="elsevierStyleItalic">&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">32 &#40;5&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">30&#46;6 &#40;4&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;025&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">32&#46;3 &#40;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">31&#46;5 &#40;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;35&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">31&#46;6 &#40;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">29&#46;8 &#40;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;015&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">C-reactive protein <span class="elsevierStyleItalic">&#40;mg&#47;dL&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">0&#46;61&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">0&#46;47&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">0&#46;57&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">0&#46;53&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">0&#46;71&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">0&#46;66&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">0&#46;41&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">0&#46;06&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Glomerular filtration <span class="elsevierStyleItalic">&#40;mL&#47;min&#47;1&#46;73 m</span><span class="elsevierStyleSup">2</span><span class="elsevierStyleItalic">&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">67&#46;8 &#91;25&#93;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">71&#46;5 &#91;23&#93;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">65&#46;9 &#91;22&#93;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">65&#46;9 &#91;19&#93;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">67&#46;4 &#91;26&#93;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">76&#46;8 &#91;21&#93;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Years of diagnosis&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">7&#46;1 &#40;5&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">HbA1c&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;027&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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