Resumen ejecutivo: Documento de posicionamiento: evaluación y manejo de la hipoglucemia en el paciente con diabetes mellitus 2020. Grupo de Trabajo de Diabetes Mellitus de la Sociedad Española de Endocrinología y Nutrición / Executive summary: Position document: Evaluation and management of hypoglycemia in the patient with diabetes mellitus 2020. Diabetes Mellitus Working Group of the Spanish Society of Endocrinology and Nutrition

Proporcionar unas recomendaciones prácticas para la evaluación y el manejo de la hipoglucemia en pacientes con diabetes mellitus. Miembros del Grupo de Trabajo de Diabetes Mellitus de la Sociedad Española de Endocrinología y Nutrición (SEEN). Las recomendaciones se formularon según el sistema Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) para establecer tanto la fuerza de las recomendaciones como el grado de evidencia. Se realizó una búsqueda sistemática en MEDLINE (PubMed) de la evidencia disponible para cada tema, y se revisaron artículos escritos en inglés y castellano con fecha de inclusión hasta el 28 de febrero de 2020. En este resumen ejecutivo incluimos la evidencia reciente incorporada desde 2013. El documento establece unas recomendaciones prácticas basadas en la evidencia acerca de la evaluación y manejo de la hipoglucemia en pacientes con diabetes mellitus.

To provide practical recommendations for the evaluation and management of hypoglycemia in patients with diabetes mellitus. Members of the Diabetes Mellitus Working Group of the Spanish Society of Endocrinology and Nutrition (SEEN). The recommendations were made based on the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system to establish both the strength of the recommendations and the level of evidence. A systematic search was made in MEDLINE (PubMed) for the available evidence on each subject, and articles written in English and Spanish with an inclusion date up to 28 February 2020 were reviewed. This executive summary takes account of the evidence incorporated since 2013. The document establishes practical evidence-based recommendations regarding the evaluation and management of hypoglycemia in patients with diabetes mellitus.

Como prevenir y tratar las hipoglucemias farmacológicas / How to prevent and treat pharmacological hypoglycemias

Mujer de 58 años con diabetes tipo 2 diagnosticada hace 3 años, en tratamiento con metformina 850mg cada 12h y glimepirida 4mg cada 24h. Tras iniciar glimepirida hace 9 meses ha incrementado 5kg su peso habitual, y presenta hipoglucemias frecuentes que han afectado a su capacidad para conducir. Su índice de masa corporal es 35,5kg/m2. Presenta además hipertensión arterial en tratamiento con telmisartán e hidroclorotiazida con adecuado control, e hipercolesterolemia en tratamiento con atorvastatina 40mg/día. Acude a consulta para revisión, aporta fondo de ojo, con resultado normal y resultados de la analítica que muestra una HbA1c de 7,0%, microalbuminuria negativa, colesterol total 149mg/dl, HDL colesterol 52mg/dl, LDL colesterol 98mg/dl y triglicéridos 123mg/dl. La tensión arterial es de 129/81mmHg, no presenta hipotensión ortostática, y la exploración neurológica periférica en miembros inferiores es normal. En resumen, se trata de una paciente joven, con una diabetes tipo 2 y obesidad, sin complicaciones crónicas, y con hipoglucemias frecuentes ¿Cómo deber ser evaluada y tratada esta paciente? (AU)

A 58 year-old woman with type 2 diabetes diagnosed 3 years before came to our clinic. Her treatment was metformin 850mg every 12hours and glimepiride 4mg every 24hours. After the initiation of glimepiride 9 months before her weight has increased 5kg, and she suffers frequent hypoglycemias which have affected her while driving. Her BMI is 35.5kg/m2. She has a normal eye fund exam. She has hypertension treated with telmisartán and hidroclorotiazide with adequate control, and also hypercholesterolemia treated with atorvastatine 40mg every 24hours. Her blood test shows an HbA1c of 7.0%, normal values of microalbuminuria, total cholesterol 149mg/dl, HDL cholesterol 52mg/dl, LDL cholesterol 98mg/dl and triglycerides 123mg/dl. Her blood pressure is 129/81mmHg, there was no orthostatic hypotension, and her peripheral neurological examination shows normal results. In summary, our case is a young woman with type 2 diabetes and obesity, without chronic complications and which has frequent hypoglycaemia. How must this woman be evaluated and treated? (AU)

How to prevent and treat pharmacological hypoglycemias.

A 58 year-old woman with type 2 diabetes diagnosed 3 years before came to our clinic. Her treatment was metformin 850 mg every 12 hours and glimepiride 4 mg every 24 hours. After the initiation of glimepiride 9 months before her weight has increased 5 kg, and she suffers frequent hypoglycemias which have affected her while driving. Her BMI is 35.5 kg/m². She has a normal eye fund exam. She has hypertension treated with telmisartán and hidroclorotiazide with adequate control, and also hypercholesterolemia treated with atorvastatine 40 mg every 24 hours. Her blood test shows an HbA1c of 7.0%, normal values of microalbuminuria, total cholesterol 149 mg/dl, HDL cholesterol 52 mg/dl, LDL cholesterol 98 mg/dl and triglycerides 123 mg/dl. Her blood pressure is 129/81 mmHg, there was no orthostatic hypotension, and her peripheral neurological examination shows normal results. In summary, our case is a young woman with type 2 diabetes and obesity, without chronic complications and which has frequent hypoglycaemia. How must this woman be evaluated and treated?

Liraglutida en el tratamiento de la diabetes tipo 2: recomendaciones para una mejor selecci¨®n de los pacientes, desde una visi¨®n multidisciplinar / Liraglutide in the treatment of type 2 diabetes: recommendations for better patients¡¯ selection from a multidisciplinary approach

Liraglutida es el primer an¨¢logo humano del p¨¦ptidosimilar al glucag¨®n tipo 1 (GLP-1) administrado unavez al d¨ªa, y con el que presenta una homolog¨ªa del97%. El f¨¢rmaco ha sido recientemente aprobadopor la European Medicines Agency y por la Food andDrug Administration para su uso en el tratamiento dela diabetes mellitus tipo 2. La aprobaci¨®n inicial espara su uso una vez al d¨ªa en combinaci¨®n, bien conmetformina o con una sulfonilurea, as¨ª como encombinaci¨®n con metformina m¨¢s una sulfonilurea ouna tiazolidindiona. En Estados Unidos, tambi¨¦n est¨¢indicada en monoterapia. Los resultados del programade estudios LEAD (Liraglutide Effect and Action inDiabetes) demuest ran que liraglutida disminuye deforma significativa la hemoglobina glucosilada(HbA1c) con muy bajo riesgo de hipoglucemia. El tratamientocon liraglutida tambi¨¦n se asocia con unap¨¦rdida de peso signifi cativa y mantenida en el tiempo,disminuci¨®n de la presi¨®n arterial sist¨®lica, mejor¨ªade la funci¨®n de las c¨¦lulas ¦Â y reducci¨®n deotros factores de riesgo cardiovascular. En este art¨ªculose revisa la evidencia m¨¢s actualizada obtenidadel programa LEAD, centr¨¢ndose en consideracionespr¨¢cticas sobre la manera de utilizar de forma ¨®ptimaesta nueva terapia para la diabetes mellitus tipo 2(AU)

Liraglutide is the first once daily human glucagonlikepeptide-1 (GLP-1) analogue, with a 97% homology.Liraglutide has recently been approved bythe European Medicines Agency and by the Foodand Drug Administration to be used in the medicalmanagement of type 2 diabetes mellitus. Initial approvalis for be using in combination with metformin,a sulphonylurea or a combination of metforminwith a sulphonylurea or thiazolidinedione. Monotherapywith liraglutide is also approved in UnitedStates. Results from the LEAD (Liraglutide Effectand Action in Diabetes) clinical trials programmeshow that liraglutide significantly lowers HbA1c, witha very low risk of hypoglycemia. Liraglutide treatmentwas also associated with significant and sustainedweight loss, decreased systolic blood pressure,improved ¦Â-cell function, and reductions inother cardiovascular risk markers. In this article wereview the most up-to-date evidence emanatingfrom the LEAD programme, focussing on practicalconsiderations on how to optimally use this new therapyfor type 2 diabetes mellitus(AU)

Effects of raloxifene therapy on circulating osteoprotegerin and RANK ligand levels in post-menopausal osteoporosis.

Previous in vitro studies suggest that the anti-resorptive effect of raloxifene might be mediated by changes in several cytokines involved in the bone remodeling process. In this context, the osteoprotegerin (OPG)- receptor activator of NF kappa B ligand (RANKL) system is considered a key component in the osteoclastogenesis regulation. The aim of this study was to determine the effects of raloxifene treatment on serum concentrations of OPG, receptor RANKL and its relationship with biochemical markers of bone turnover and bone mineral density (BMD) in previously untreated women with post-menopausal osteoporosis. We selected 47 post-menopausal women (mean age 63+/-7 yr) with densitometric criteria of osteoporosis. We determined at baseline, 3, 6, and 12 months anthropometric parameters, biochemical markers of bone turnover, serum levels of 25(OH) D, serum levels of OPG and RANKL. BMD (dual-energy x-ray absorptiometry) in lumbar spine (LS) femoral neck and total hip was measured at baseline and 12 months after raloxifene (60 mg/day) treatment. Serum levels of OPG decreased in the 3rd and 6th month of treatment (p<0.001) and returned to basal levels in the 12th month. There was a significant decrease of RANKL levels and OPG/RANKL ratio after 1 yr of raloxifene treatment. In addition, BMD in LS increased significantly (2.5%) in the 12th month of treatment (p=0.031). Finally, the biochemical markers of bone turnover (total alkaline phosphatase, bone alkaline phosphatase, osteocalcin, tartrate-resistant acid phosphatase, urine cross-linked carboxi-terminal telopeptide of type I collagen) decreased significantly from the 3rd month of treatment. In conclusion, our results support the hypothesis that raloxifene may inhibit osteoclast activity, at least partly modulating the OPG-RANKL system.

Importancia del IGF-I en el metabolismo óseo / Importance of IGF-I in bone metabolism

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Performance of quantitative ultrasound in the discrimination of prevalent osteoporotic fractures in a bone metabolic unit.

There is a growing interest in ultrasound evaluation of bone status as an alternative to the measurement with dual X-ray absorptiometry (DXA), due to its low cost, portability, and nonionizing radiation. The aim of our study was to investigate the relation among DXA, QUS, clinical, anthropometric, and lifestyle factors, and to determine QUS cutoff values in order to discriminate fractures in patients referred to the Bone Metabolic Unit at an Endocrinology Service. We studied 300 patients (281 females and 19 males; age 58 +/- 11 years) referred for evaluation of osteoporosis. In all cases we determined basic anthropometric parameters, a clinical history including previous osteoporotic fractures and risk factors for osteoporosis, and QUS parameters in calcaneus (Hologic Sahara), and BMD in lumbar spine (LS) and femoral neck (FN), by DXA (Hologic QDR 1000). Using the WHO densitometric criteria, 37, 46.7, and 16.3% of our population were osteoporotic, osteopenic, and normal, respectively. A QUI T-score

Prevención y tratamiento de la osteoporosis / Prevention and treatment of osteoporosis

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Performance of COLIA1 polymorphism and bone turnover markers to identify postmenopausal women with prevalent vertebral fractures.

Some studies have suggested that bone turnover markers (BTM) and collagen type I alpha 1 gene (COLIA1) may be useful in the prediction of rates of future bone loss, and may therefore provide information about fracture risk. Our study aimed to examine the association of the COLIA1 genotype with the risk of vertebral fracture and to investigate the predictive value of this genetic factor in comparison with bone mineral density (BMD) and BTM, in ambulatory postmenopausal Spanish women. We determined the COLIA1 polymorphism by polymerase chain reaction, BMD by dual-energy X-ray absorptiometry and BTM in 43 postmenopausal women with prevalent vertebral fracture and a control group of 101 postmenopausal women without fracture. There was a significant overrepresentation of the 'T' allele in fractured women ( p = 0.029). BTM exhibited no differences between women with or without fractures or COLIA1 genotype groups. After adjusting for all other variables, the osteoporosis densitometric criteria variable was the most strongly associated with fracture (OR = 5 [1.8-13.3]) followed by COLIA1 (OR = 2.1 [1-4.3] per copy of the 'T' allele). Our study shows that COLIA1 is associated with prevalent vertebral fracture independently of bone mass, and the performance of this genetic factor to assess prevalent vertebral fracture is better than bone turnover markers.

Relation between vitamin D insufficiency, bone density, and bone metabolism in healthy postmenopausal women.

Although only few postmenopausal women exhibit biochemical signs of hypovitaminosis D, vitamin D insufficiency has been shown to have adverse effects on bone metabolism and could be an important risk factor for osteoporosis and fracture. We determined serum levels of 25-hydroxyvitamin D [25(OH)D], intact parathyroid hormone (iPTH), bone turnover markers, dietary calcium intake, and bone mineral density (BMD; measured by dual X-ray absorptiometry) in 161 consecutive ambulatory women, healthy except for osteoporosis, referred to a bone metabolic unit. The prevalence of vitamin D insufficiency [25(OH)D < or = 15 ng/ml] was 39.1%. 25(OH)D was lower in the osteoporotic subjects (15.7 +/- 5.3 ng/ml vs. 21.8 +/- 9.7 ng/ml; p < 0.001). After controlling for all other variables, lumbar spine (LS) BMD was found to be significantly associated with 25(OH)D, body mass index (BMI), and years after menopause (YSM) (R2 = 0.253; p < 0.001). For femoral neck (FN), significant independent predictors of BMD were YSM, BMI, iPTH, and 25(OH)D (R2 = 0.368; p < 0.001). The probability of meeting osteoporosis densitometric criteria was higher in the vitamin D insufficiency group (odds ratio [OR], 4.17, 1.83-9.48) after adjusting by YSM, BMI, iPTH, and dietary calcium intake. Our study shows that vitamin D insufficiency in an otherwise healthy postmenopausal population is a common risk factor for osteoporosis associated with increased bone remodeling and low bone mass.

The contribution of IGF-I to skeletal integrity in postmenopausal women.

OBJECTIVES: The pathogenic role of the decline in serum concentrations of IGF-I in postmenopausal osteoporosis is not fully elucidated. We investigated the associations among IGF-I, bone mineral density (BMD), ultrasound parameters and prevalence of vertebral fractures in postmenopausal women. DESIGN: A cross-sectional study. PATIENTS: One hundred and fifty-four ambulatory postmenopausal women (61 +/- 7 years) referred for osteoporosis screening. MEASUREMENTS: IGF-I was measured by radioimmunoassay and BMD using dual-energy X-ray absorptiometry. Broadband ultrasound attenuation (BUA) and speed of sound (SOS) at calcaneus were measured by a quantitative ultrasound system. RESULTS: IGF-I was significantly lower in osteoporotic subjects and correlated positively with BMD, BUA and SOS. After adjusting for age, years since menopause and body mass index, IGF-I accounted for 8.5% of the variance at lumbar spine BMD, 4.6% at femoral neck and 7.1% at calcaneal BUA. BUA was associated with IGF-I independently of BMD. IGF-I was lower in women with vertebral fractures (91 +/- 39 microg/l vs. 114 +/- 44 microg/l; P = 0.003). The osteoporosis densitometric criteria (t-score < or = -2.5 SD) was the most strongly independent associated variable with prevalent vertebral fractures [odds ratio (OR): 3.3 (1.4-7.6)], followed by IGF-I levels below 75th percentile [OR: 3 (1-8.8)]. CONCLUSIONS: Our study shows that IGF-I is strongly associated with bone mineral density and reflects aspects of bone quality. The contribution of IGF-I to skeletal integrity in postmenopausal women is clinically relevant.

Utilidad de los marcadores de remodelado óseo / Utility of bone remodelling markers

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Evolución de la masa ósea en una mujer con hiperprolactinemia / Bone mass changes in a woman with increased prolactinemia

Presentamos el caso clínico de una mujer de 31 años de edad que fue diagnosticada de osteoporosis secundaria a hiperprolactinemia producida por un macroadenoma hipofisario resistente a tratamiento y la evolución de la masa ósea antes y después de tratamiento con terapia hormonal sustitutiva. (AU)

[Usefulness of bone densitometry in the evaluation of primary hyperparathyroidism]. / Utilidad de la densitometría ósea en la evaluación del hiperparatiroidismo primario.

BACKGROUND: In recent years, the clinical profile of primary hyperparathyroidism (PH) is predominantly characterized by mild or asymptomatic forms. In this context, the effects of the PH on bone metabolism reach a growing importance in the adoption of therapeutic decisions. PATIENTS AND METHODS: 116 patients with PH were studied, 95 women (25 premenopausal, 70 postmenopausal) and 21 males. In all cases parathyroidectomy criteria were evaluated. Bone mineral density (BMD) was determined in 71 patients in lumbar spine (LS) and femoral neck by dual-X-Ray absorptiometry (DXA) and the influence of this measurement in the decision of surgical treatment was analyzed. RESULTS: The patients with PH showed a significant reduction of BMD at all sites (p < 0.001) and 71.8% met osteoporosis densitometric criteria. The most frequent parathyroidectomy criteria was the presence of specific clinical manifestations (51.7%) followed by decrease of the BMD in LS (49.3%). The probability of meeting criteria for surgical treatment was significantly higher in patients in which BMD was measured (odds ratio: 3.09 [1.03-9.22]; p = 0.036). CONCLUSIONS: In its current presentation, PH presents a significant decrease of bone mass. The systematic performance of bone densitometry has a decisive influence in its appropriate management.