[Continuous glucose monitoring. Utility and indications]. / Monitoreo continuo de glucosa. Utilidad e indicaciones.

An adequate glycemic control prevents and/or delays the development and/or progression of chronic complications in patients with diabetes mellitus (DM). To achieve this control, it is necessary to adjust insulin doses, in type 1 or insulinized type 2 DM persons, based on traditional capillary glucose self-monitoring, which has limitations to generate an adequate data record, is invasive and has low adherence. In contrast, new continuous glucose monitoring (CGM) systems provide more complete and dynamic information, and better compliance. In these systems, a subcutaneous sensor continuously sends glucose values which are captured and stocked by a receptor module. Real-time models (CGMRT) allow continuous and real-time readings of interstitial glucose, whereas CGM-Flash/EI systems require lector approach to sensor module performing intermittent scanning. CGM shows if glycemic levels are increasing or decreasing and how fast it is happening (tendency). CGM decreases glycosylated hemoglobin between 0.53% and 1.0%, as well as time in hypoglycemia by 38%, increasing the time in range of glucose levels, in patients with high adherence. The objectives of this review are to describe the glycemic homeostasis, to evaluate the accuracy of the CGM to interpret the data adequately and finally, based on the information provided by these novel monitoring systems, to suggest a practical way to be added to the traditional intensive insulin therapy.

Efficacy of anthropometric measures for identifying cardiovascular disease risk in adolescents: review and meta-analysis.

INTRODUCTION: To compare the ability of Body Mass Index (BMI), waist circumference (WC) and waist to height ratio (WHtR) to estimate cardiovascular disease (CVD) risk levels in adolescents. EVIDENCE ACQUISITION: A systematic review and meta-analysis was performed after a database search for relevant literature (Cochrane, Centre for Review and Dissemination, PubMed, British Nursing Index, CINAHL, BIOSIS citation index, ChildData, metaRegister). EVIDENCE SYNTHESIS: The study included 117 records representing 96 studies with 994,595 participants were included in the systematic review, 14 of which (13 studies, N.=14,610) were eligible for the meta-analysis. The results of the meta-analysis showed that BMI was a strong indicator of systolic blood pressure, diastolic blood pressure, triglycerides, high-density lipoprotein cholesterol and insulin; but not total cholesterol, low-density lipoprotein or glucose. Few studies were eligible for inclusion in the meta-analysis considering WC or WHtR (N.≤2). The narrative synthesis found measures of central adiposity to be consistently valid indicators of the same risk factors as BMI. CONCLUSIONS: BMI was an indicator of CVD risk. WC and WHtR were efficacious for indicating the same risk factors BMI performed strongly for, though there was insufficient evidence to judge the relative strength of each measure possibly due to heterogeneity in the methods for measuring and classifying WC.

The Metreleptin Effectiveness and Safety Registry (MEASuRE): concept, design and challenges.

BACKGROUND: Metreleptin, a recombinant analog of human leptin, is an approved therapy, adjunct to diet, to treat the metabolic complications of leptin deficiency in patients with lipodystrophy - a group of rare diseases characterized by a paucity of adipose tissue. MEASuRE (Metreleptin Effectiveness And Safety Registry) is a post-authorization, voluntary registry that gathers long-term safety and effectiveness data on metreleptin. Here, we present the aims and evolution of MEASuRE. METHODS: MEASuRE was established to collect data from patients receiving commercially supplied metreleptin in the United States (US) and European Union (EU). MEASuRE aims to determine the incidence and severity of safety events and describe the clinical characteristics and therapeutic outcomes in the metreleptin-treated population. A key feature of MEASuRE is that it accumulates data from different sources to meet post-authorization objectives. US data are received directly from treating physicians via a contract research organization-mediated electronic data capture system. In the EU, data are received via the European Registry of Lipodystrophies managed by the European Consortium of Lipodystrophies (ECLip), a platform established by researchers and physicians to advance the knowledge of lipodystrophy. MEASuRE complies with applicable regulatory requirements governing privacy, and the storage, management, and access of data. RESULTS: Leveraging processes, infrastructure, and data from the ECLip registry presented several challenges that were addressed during MEASuRE's development, including the expansion of the ECLip registry to accommodate MEASuRE-specific data elements, extensive data matching processes to ensure data consistency regardless of source, and rigorous data validation following the amalgamation of global data. Through the support of ECLip, MEASuRE is now a fully operational registry with the capacity for gathering and integrating standardized US- and EU-derived data. As of 31st October 2022, 15 US and four EU sites have participated in the MEASuRE, enrolling 85 patients globally. CONCLUSIONS: Our experiences show that a post-authorization product registry can be successfully integrated into an existing patient registry. We propose that, through collaboration with existing registries and use of their established resources, patient enrolment timelines and data collection for new registries can be expedited. The learnings presented here may be applicable to other registries with similar objectives. TRIAL REGISTRATION: NCT02325674; Registered 25 December 2014 - Retrospectively registered'. https://clinicaltrials.gov/ct2/show/NCT02325674 .

Low glomerular filtration rate values are associated with higher TSH in an elderly population at high cardiovascular disease risk.

Background: Hypothyroidism is associated with impaired glomerular filtration rate (GFR), a recognized cardiovascular disease (CVD), and mortality risk factor. In older adults, this association remains unexplored. We aimed to determine the relationship of elevated TSH with GFR in an elderly population at high CVD risk. Methods: Older adults (age>65ys) with high CVD risk defined by two or more CVD risk factors: smoking (S), high blood pressure (HBP), high total cholesterol, low HDL cholesterol, diabetes (DM), metabolic syndrome or previous cardiovascular event, were prospectively included at our ambulatory Endocrine Clinic. Patients under levothyroxine or thyroid disease were excluded. TSH> 6mU/l defined subclinical hypothyroidism (ScH) with normal free T4 levels. Estimated GFR was calculated by the Berlin-Initiative Study (BIS)-1 formula for elderly population. Urinary albumin to creatinine ratio (uACR), IL-6 and TNF-α, and Carotid intima-media thickness (CIMT) were also determined. The U Mann-Whitney test, the Spearman test, and multiple linear regression were used as statistical tests. Results: Finally 246 patients (68% females) were included and 20 (8%) had ScH. This group, was older (median, Q1-Q3: 77,72-78; 72,68-77 years, p=0.01) and DM was less frequent than in the euthyroid group (35 vs 58%, p=0.039). Lower fasting glucose (-20%,p=0.01), GFR (-14%,p=0.01) and freeT4 (-10%,p<0.001) were found compared to euthyroid patients. A higher prevalence of Kidney failure was found in ScH (80 vs. 46%, p=0.003) vs. euthyroid individuals. Significant correlations with GFR were detected: age (r-0.482,p<0.001), TSH (r-0.172,p=0.004), IL-6 (r-0.150,p=0.047), TNF-α (r-0.274,p<0.001), uACR (r-0.170,p=0.009) and CIMT(r-0.189,p=0.004). By multiple linear regression, in a model adjusted by age, sex, BMI, uACR, S, DM, TNF-α and HBP, TSH (Bst -0.14, p=0.023, R2 = 0.25) was found an independent predictor of GFR. Conclusion: In older adults with high CVD risk, ScH is associated with lower renal function, and this relationship is present regardless of other cardiometabolic risk factors. These results suggest that ScH could contribute to low GFR and excess CVD risk, although this hypothesis should be addressed in longitudinal studies.

[Triglycerides/HDL-cholesterol ratio: in adolescents without cardiovascular risk factors]. / Indice triglicéridos/HDL-colesterol: en una población de adolescentes sin factores de riesgo cardiovascular.

Triglycerides/HDL-cholesterol ratio (TG/HDL) is an easy resource determination and it has good correlation with the HOMA index in adults. Due to physiological insulin resistance (IR) in adolescence it is necessary to find markers of IR independent of age, sex and pubertal stage. The objective was to identify reference values of TG/HDL ratio in a population of adolescents without cardiovascular risk factors. We evaluated 943 adolescents, 429 females and 514 males between 11 and 14. Anthropometric measures were determined and body mass index was calculated (BMI). Blood was extracted after 12 hours of fasting to determine glucose, triglycerides, HDL. The metabolic syndrome (MS) was diagnosed according to criteria of NCEP/ATP III modified by Cook. We excluded adolescents with MS or any component of it. We evaluated 562 adolescents (289 women and 273 men) with a weight of 48.91 +/- 6.51kg, BMI: 18.95 +/- 1.78, systolic blood pressure of 108.12 +/- 13.60 mmHg, diastolic blood pressure: 63.82 +/- 9.43 and waist circumference: 65.09 +/- 4.54 cm. TG/HDL ratio was 1.25 +/- 0.43, with a 95 percentile of 2.05. In adults, TG/HDL ratio greater than 3 is a marker of insulin resistance. We believe that a higher value to 2.05 might be a good index of insulin resistance in adolescence. TG/HDL ratio has the advantage of being methodologically simpler, more economical and independent of pubertal stage.

Cardiometabolic risk factors as apolipoprotein B, triglyceride/HDL-cholesterol ratio and C-reactive protein, in adolescents with and without obesity: cross-sectional study in middle class suburban children.

BACKGROUND: The prevalence of obesity (OB), overweight (OW), and metabolic syndrome (MS) has increased worldwide. That imposes a substantial risk for type 2 diabetes and premature cardiovascular disease. However, to date no unified criteria exist to asses risk or outcomes in children and adolescents. OBJECTIVES: To establish the presence of OB/OW and MS and risk factors for cardiovascular disease in adolescents. DESIGN AND SUBJECTS: Male (n = 514) and female (n = 429) adolescents from high school were studied (11-14 yr). Weight, height, body mass index (BMI), waist circumference (WC), and blood pressure were determined in all subjects. Glucose, lipoprotein profile, apolipoprotein B (apoB), and high-sensitivity C-reactive protein (hs-CRP) levels were measured. Triglyceride/high-density lipoprotein-cholesterol (TG/HDL-cholesterol) ratio was calculated. RESULTS: The frequency of OB/OW and MS were 22.2 and 3.7%, respectively. In comparison to healthy adolescents, TG/HDL-cholesterol ratio was increased in OB/OW (2.9 ± 2.5 vs. 1.6 ± 1.0) and MS groups (4.0 ± 2.5 vs. 1.6 ± 0.9), p < 0.001. OB/OW adolescents presented higher values of hs-CRP in comparison to non-obese, median (range): 1.9 (0.1-9.4) vs. 1.4 (0.1-9.9), mg/L, p < 0.001. ApoB (mean ± SD) was 71 ± 21 mg/dL in MS group and 59 ± 17 mg/dL in those without MS (p < 0.001). TG/HDL-cholesterol ratio positively correlated with BMI (r = 0.18, p < 0.001), WC (r = 0.24, p < 0.001), and apoB (r = 0.24, p < 0.001); hs-CRP correlated with WC (r = 0.14, p < 0.001) and BMI (r = 0.17, p < 0.001). CONCLUSIONS: Even when the frequency of OB, OW, and MS in adolescents was low, those subjects presented an atherogenic lipoprotein. These findings emphasize the importance to evaluate cardiovascular risk factors in adolescents to assess strategies to prevent future disease.

Heart Failure and Diabetes: Perspective of a Dangerous Association.

The relationship between diabetes and risk of heart failure has been described in previous trials, releasing the importance of the hyperglycemic state that, added to other risk factors, favors the development of coronary heart disease. The mechanism by which, in the absence of hypertension, obesity and/or dyslipidemia, diabetic patients develop cardiomyopathy has been less studied. Recently, the Sodium Glucose Co-transporter type 2 inhibitors (SGLT2 inhibitors) used for the treatment of heart failure patients with or without diabetes has been a breakthrough in the field of medicine. This review describes the established pathophysiology of diabetic cardiomyopathy and SGLT2 inhibitors, their mechanisms of action, and benefits in this group of patients.

Glycemic variability and cardiovascular disease in patients with type 2 diabetes.

Glycated hemoglobin is currently the gold standard for assessment of long-term glycemic control and response to medical treatment in patients with diabetes. Glycated hemoglobin, however, does not address fluctuations in blood glucose. Glycemic variability (GV) refers to fluctuations in blood glucose levels. Recent clinical data indicate that GV is associated with increased risk of hypoglycemia, microvascular and macrovascular complications, and mortality in patients with diabetes, independently of glycated hemoglobin level. The use of continuous glucose monitoring devices has markedly improved the assessment of GV in clinical practice and facilitated the assessment of GV as well as hypoglycemia and hyperglycemia events in patients with diabetes. We review current concepts on the definition and assessment of GV and its association with cardiovascular complications in patients with type 2 diabetes.

[New generation of insulins: glargine U300. Summary of clinical evidence]. / Nueva generación de insulinas: glargina U300. Resumen de evidencia clínica.

Type 2 diabetes is a chronic, progressive disease with increasing prevalence and still late diagnostic. This leads to an increase in the incidence of chronic complications, with signifi cantly increasing health costs. There is also a delay in the onset of insulin therapy in patients with type 2 diabetes for causes related to both patients and physicians. Despite advances in treatment, a low proportion of patients achieve adequate glycemic control. The high hypoglycemia prevalence, consequence of insulin, has led to the development of a new generation long-acting basal insulins to achieve a more stable and prolonged action profile, reducing the variability and risk of hypoglycemia. The EDITION program evaluated the efficacy and safety of glargine U300 compared to glargine U100 in patients with type 1 and 2 diabetes at different stages of the disease. Gla-300 is a new formulation of insulin glargine which has a more stable and prolonged pharmacokinetic and pharmacodynamic profile. Gla-300 demonstrated efficacy and tolerability comparable to glargine U100, with a significant decrease in the risk of hypoglycemia, at night and in 24 hours, providing greater flexibility in the injection schedule, with a window of 6 hours. No increase in weight was observed compared to glargine U100. Bright study (2018) compared glargine U300 vs. degludec U100, demonstrating greater benefit in relation to the risk of hypoglycemia with Gla-300 during titration period. Gla-300 is a last-generation basal insulin, available to improve metabolic control, with a lower risk of hypoglycemia.

La diabetes mellitus tipo 2 tiene evolución crónica y progresiva, prevalencia creciente y aún es diagnosticada tardíamente. Esto conlleva mayor incidencia de complicaciones crónicas, con incremento de costos en salud. Existe retraso en el inicio de insulinoterapia por causas relacionadas tanto al paciente como al médico. A pesar de los avances en su tratamiento, una baja proporción de enfermos logra control glucémico adecuado. La alta prevalencia de hipoglucemia en pacientes insulino-tratados, impulsó el desarrollo de una nueva generación de insulinas basales de acción prolongada, mayor estabilidad con menor variabilidad y riesgo de hipoglucemias. El programa EDITION evaluó la eficacia y seguridad de glargina U300 vs. glargina U100 en pacientes con diabetes tipo 1 y 2, en distintas etapas de la enfermedad. Glargina U300 es una nueva formulación de insulina glargina con perfil farmacocinético y farmacodinámico más estable y prolongado que glargina U100. Glargina U300 demostró eficacia y tolerabilidad comparable a glargina U100, con descenso significativo del riesgo de hipoglucemias nocturnas y en 24 horas, aportando mayor flexibilidad en el horario de inyección, con una ventana de 6 horas. Además, no se observó mayor aumento de peso que con glargina U100. El estudio Bright (2018) comparó glargina U300 vs. degludec U100, demostrando mayor beneficio en relación al riesgo de hipoglucemia con Gla-300 durante el período de titulación. Gla-300 es una insulina basal de última generación, disponible para mejorar el control metabólico, con menor riesgo de hipoglucemia.

Long-term efficacy of leptin replacement in patients with generalized lipodystrophy.

Ectopic fat accumulation has been implicated as a contributing factor in the abnormal metabolic state of obesity. One human model of ectopic fat deposition is generalized lipodystrophy. Generalized lipodystrophy is a rare disorder characterized by a profound deficiency of adipose tissue with resultant loss of triglyceride storage capacity and reduced adipokines, including leptin. Subjects with generalized lipodystrophy and reduced leptin levels often have an increased appetite leading to hyperphagia. Excess fuel consumption, coupled with a lack of adipose tissue, contributes to the significant ectopic triglyceride accumulation in the muscle and liver seen in these subjects. This ectopic fat, along with the deficiency in leptin signaling and perhaps other adipokines, likely contributes to insulin resistance, diabetes, and hepatic steatosis. We report here the long-term effects of leptin replacement in a cohort of these subjects. Fifteen patients with generalized lipodystrophy were treated with twice-daily recombinant methionyl human leptin (r-metHuLeptin) for 12 months. We evaluated metabolic parameters at baseline and every 4 months. Antidiabetes medications were decreased or discontinued as necessary. Reductions were seen in serum fasting glucose (from 205 +/- 19 to 126 +/- 11 mg/dl; P < 0.001), HbA1c (from 9 +/- 0.4 to 7.1 +/- 0.5%; P < 0.001), triglycerides (from 1,380 +/- 500 to 516 +/- 236 mg/dl; P < 0.001), LDL (from 139 +/- 16 to 85 +/- 7 mg/dl; P < 0.01), and total cholesterol (from 284 +/- 40 to 167 +/- 21 mg/dl; P < 0.01). HDL was unchanged (from 31 +/- 3 to 29 +/- 2 mg/dl; P = 0.9). Liver volumes were significantly reduced (from 3,663 +/- 326 to 2,190 +/- 159 cm3; P < 0.001), representing loss of steatosis. Decreases were seen in total body weight (from 61.8 +/- 3.6 to 57.4 +/- 3.4 kg; P = 0.02) and resting energy expenditure (from 1,929 +/- 86 to 1,611 +/- 101 kcal/24 h; P < 0.001). R-metHuLeptin led to significant and sustained improvements in glycemia, dyslipidemia, and hepatic steatosis. Leptin represents the first novel, effective, long-term treatment for severe forms of lipodystrophy.

Metreleptin Treatment in Three Patients with Generalized Lipodystrophy.

Generalized lipodystrophy (GL) is a rare inherited or acquired disease characterized by widespread loss of subcutaneous fat, leading to leptin deficiency, ectopic fat deposition, and severe metabolic abnormalities. Previous studies have shown the benefit of leptin replacement (metreleptin) in ameliorating metabolic complications, but little is known about the experience of metreleptin treatment outside of a research setting. We report on post-marketing clinical experience with metreleptin therapy in three patients with GL and marked hypoleptinemia, uncontrolled diabetes, and hypertriglyceridemia. After metreleptin treatment for 12-168 weeks, the mean glycated hemoglobin decreased from 10.9% to 5.8%, and serum triglycerides were normalized (a mean decline of 90%). These benefits were observed within weeks of starting therapy, were durable, and were accompanied by subjective improvements in quality of life, decreased need for concomitant medications, and no significant adverse effects. Metreleptin was safe and effective in normalizing certain severe metabolic abnormalities in the clinic setting.

La pandemia Covid-19 y la continuidad de los procesos de formación de los profesionales de la salud: virtualización de las experiencias de aprendizaje en la Sociedad Argentina de Diabetes / The Covid-19 pandemic and the continuity of the training processes of health professionals: virtualization of learning experiences in the Argentine Society of Diabetes

El año 2020 se nos presentó a todos como un año diferente en el que nos vimos obligados, individualmente y como comunidad, a generar formas distintas de comunicación e intercambio. Transcurría febrero y los docentes de la Sociedad Argentina de Diabetes (SAD) generábamos propuestas para desarrollar durante el año, compartiendo reuniones y tratando de responder inquietudes surgidas de los debates, planificando los temas, a quiénes dirigirnos o qué competencias queríamos desarrollar. Pero marzo nos sorprendió con el contexto de aislamiento sanitario producto de la pandemia y esto generó un desafío en materia educativa con más incertidumbres que certezas, dentro de un marco de mucha angustia en lo personal y laboral.

The long-term effect of recombinant methionyl human leptin therapy on hyperandrogenism and menstrual function in female and pituitary function in male and female hypoleptinemic lipodystrophic patients.

Lipodystrophy patients are hypoleptinemic and insulin resistant. Women have enlarged polycystic ovaries, hyperandrogenism, and amenorrhea. We have determined the role of correction of hypoleptinemia on these metabolic and neuroendocrine parameters. Ten females and 4 males with generalized lipodystrophy were treated with recombinant methionyl human leptin (r-metHuLeptin) in physiologic doses in an open-labeled study for a period of 12 and 8 months, respectively. In the female group, serum free testosterone decreased from 39.6 +/- 11 to 18.9 +/- 4.5 ng/dL (P < 0.01) and serum sex hormone binding globulin increased from 14 +/- 2.5 to 25 +/- 4.8 nmol/L (P < 0.02). Luteinizing hormone (LH) responses to LH releasing hormone were more robust after therapy and significantly changed in the youngest group of 3 female patients (P < 0.01). Ovarian ultrasound showed a polycystic ovarian disease pattern in all patients and did not change after therapy. Eight of the 10 patients had amenorrhea prior to therapy and all 8 developed normal menses after therapy. In the male group, serum testosterone tended to increase from 433 +/- 110 to 725 +/- 184 ng/dL (P = 0.1) and sex hormone binding globulin also increased from 18.25 +/- 2.6 to 27 +/- 1.7 nmol/L (P < 0.04) following r-metHuLeptin therapy. Serum LH response to LH releasing hormone did not show significant changes. Five additional hypoleptinemic male subjects with minimal metabolic abnormalities underwent normal pubertal development without receiving r-metHuLeptin therapy. In both genders, insulin-like growth factor increased significantly and there were no differences in growth hormone, thyroid, or adrenal hormone levels following r-metHuLeptin therapy. Glycemic parameters significantly improved after r-metHuLeptin therapy in both groups. Hypoglycemic medications were discontinued in 7 of 12 patients and dramatically reduced in 5 patients. r-metHuLeptin therapy plays an important role in insulin sensitivity. In females, it plays an additional role in normalizing menstrual function. This is likely to occur both from increasing insulin sensitivity and from restoring LH pulsatility. The persistent hypoleptinemic state in these subjects did not inhibit pubertal development.

Myxedema madness complicating postoperative follow-up of thyroid cancer.

Although hypothyroidism is associated with an increased prevalence of psychiatric manifestations, myxedema madness is rarely observed. We report the case of a 62-year-old woman with no prior history of psychiatric disorders, who presented to the emergency department with psychomotor agitation 6 weeks after total thyroidectomy for papillary thyroid cancer. Serum thyroid stimulating hormone (TSH) on admission was 62.9 mIU/L and free T4 was < 0.35 ng/dL, indicating severe hypothyroidism. After ruling out other possible causes, the diagnosis of myxedema madness was considered; hence, antipsychotic drug treatment and intravenous levothyroxine were prescribed. Behavioral symptoms returned to normal within 4 days of presentation, while levels of thyroid hormones attained normal values 1 week after admission. Recombinant TSH (Thyrogen®) was used successfully to prevent new episodes of mania due to thyroid hormone withdrawal in further controls for her thyroid cancer. This case illustrates that myxedema madness can occur in the setting of acute hypothyroidism, completely reverting with levothyroxine and antipsychotic treatment. Recombinant TSH may be a useful tool to prevent myxedema madness or any severe manifestation of levothyroxine withdrawal for the follow-up of thyroid cancer.

Ten years cardiovascular risk estimation according to Framingham score and non HDL-cholesterol in blood donors.

UNLABELLED: Cardiovascular disease (CVD) is currently the primary cause of morbidity and mortality. AIMS: (1) Assess the 10 years risk for CVD in Argentinean blood donors, according to Framingham score (updated by ATP III), (2) evaluate the prevalence of the MS, (3) evaluate non HDL-cholesterol level in this population as other risk for CVD. MATERIALS AND METHODS: A prospective, epidemiological, transversal study was performed to evaluate 585 volunteer blood donors for two years. Non HDL-C was calculated as total cholesterol minus HDL-C and we evaluated the 10 years risk for CVD according to Framingham score (updated by ATP III). RESULTS: Metabolic syndrome prevalence was estimated according to ATP III and IDF criteria. Non HDL-C was (media±SD) 178.3±48.0 mg/dl in participants with MS and 143.7±39.3 mg/dl without MS (ATPIII) and 160.1±43.6 mg/dl in participants with MS and 139.8±43.1 mg/dl without MS (IDF). Participants with MS presented an OR of 3.1; IC 95% (2-5) of CVD according to de Framingham score. CONCLUSION: Individuals with MS and elevated non HDL-C are at a higher estimated risk for cardiovascular events in the next 10 years according to the Framingham risk score.

Association between worse metabolic control and increased thyroid volume and nodular disease in elderly adults with metabolic syndrome.

BACKGROUND: Metabolic syndrome has been associated with nodular goiter. Our aim was to evaluate which metabolic parameters in elderly patients with metabolic syndrome are associated with thyroid enlargement or increased prevalence of thyroid nodules. METHODS: In this cross-sectional study, 77 patients >65 years of age with metabolic syndrome were included. We evaluated the presence of thyroid nodules and thyroid volume by ultrasonography and several biochemical, metabolic and anthropometric parameters. Only patients with thyrotropin (thyroid-stimulating hormone, TSH) levels between 0.3 and 6 mU/L were included. We further divided subjects into two groups-type 2 diabetes mellitus (T2DM) and non-T2DM and established comparisons between them. RESULTS: Among all parameters analyzed we found a significant correlation between glycated hemoglobin (HbA1c) and volume (r=0.261, P=0.027) or number of nodules (r=0.266, P=0.023). Neither sex, age, body mass index (BMI), metformin, nor levothyroxine use were associated with thyroid volume or nodularity. Within the whole cohort, those patients with T2DM had larger thyroid volumes compared to non-T2DM [median (confidence interval, CI) 6.976 (5.220-10.789) vs. 5.034 (3.796-6.034) mL, P<0.008). Furthermore, a larger proportion of T2DM patients presented thyroid volumes >5.8 mL [69 vs. 23%, P<0.001; odds ratio=7.25 (CI 2.04-25.56)]. CONCLUSIONS: In elderly patients with metabolic syndrome, worse metabolic control, represented by higher HbA1c levels, was found associated to increased prevalence of thyroid nodules and larger thyroid volume. Moreover, within the whole metabolic syndrome group, patients with T2DM had the largest thyroid volumes.

Monitoreo continuo de glucosa: indicaciones, interpretación de datos y toma de decisiones terapéuticas. Recomendaciones de expertos / Continuous glucose monitoring: indications, data interpretation and making therapeutic decisions. Expert recommendations

Las herramientas para evaluar el grado de control glucémico se modificaron últimamente. La emoglobina glicosilada (HbA1c), parámetro de referencia (gold standard), refleja el control glucémico de los últimos tres meses de manera retrospectiva, sin expresar la variabilidad glucémica. El automonitoreo glucémico capilar (AGC) brinda información inmediata y prospectiva, pero dispone de pocos datos glucémicos para generar promedios y desviaciones estándares representativas. No detecta tendencias y tiene limitaciones para obtener datos nocturnos o durante la actividad física. Es invasivo y muchas veces rechazado. Contrariamente, el monitoreo continuo de glucosa (MCG) mide la glucosa instantáneamente, y muestra sus tendencias y su variabilidad en forma continua, incorporando nuevas métricas de control. Mediante el perfil ambulatorio de glucosa (PAG) se analizan los patrones del control glucémico durante el sueño, los ayunos prolongados, la actividad física y las intercurrencias, expresándolos como curvas con sus desviaciones estándar durante períodos de horas (8 a 24 horas) o días (7, 14, 30 y 90 días). El PAG contiene las siguientes métricas: porcentaje de tiempo en rango TIR (del inglés, time in range), porcentaje de tiempo por encima del rango TAR (del inglés, time above range), porcentaje de tiempo por debajo del rango o hipoglucemia TBR (del inglés, time below range) y coeficiente de variabilidad (%CV). La información continua permite tomar decisiones inmediatas, ya sea con la ingesta de carbohidratos o con la aplicación de insulina. El MCG con terapéuticas insulínicas inyectables (TII) o bomba portable de insulina (BPI) es una herramienta muy útil y complementaria para el tratamiento de la diabetes mellitus tipo 1 (DM1) y la DM2 en la insulinoterapia. Su utilización se asoció con descensos significativos en la HbA1c, disminución de la variabilidad glucémica, reducción de las hipoglucemias totales y nocturnas, y mejoría de la calidad de vida en estos pacientes. Nuestro propósito como grupo de expertos es generar una guía práctica para regular la implementación del MCG.

The tools to assess the degree of glycemic control were modified lately. Glycosylated hemoglobin (HbA1c), the gold standard, reflects the glycemic control of the last 3 months retrospectively, without expressing glycemic variability. Selfblood glucose monitoring (SBGM) provides immediate and prospective information, but has little glycemic data to generate representative averages and standard deviations. It does not detect trends and has limitations to obtain nocturnal data or during physical activity. It is invasive and often rejected. On the contrary, continuous glucose monitoring (CGM), allows to measure glucose instantly, shows your trends and variability continuously, incorporating new control metrics. The ambulatory glucose profile (AGP) analyzes the patterns of glycemic control during sleep, prolonged fasting, physical activity and intercurrences, expressing them as curves with their standard deviations during periods of hours (8 to 24 hours) or days (7, 14, 30 and 90 days). The AGP contains the following metrics: percentage time in range (TIR), percentage time above range mg/dl (TAR), percentage time below range or hypoglycemia (TBR) and coefficient of variation (%CV). CGM with IIT or continuous subcutaneous insulin infusion (CSII), is a very useful and complementary tool for the treatment of DM1 and DM2 in insulin therapy. Its use was associated with significant decreases in HbA1c, decreased glycemic variability, reduction of total and nocturnal hypoglycemia and improvement of the quality of life in these patients. Our aim as a group of experts is to generate a practical guide to regulate the implementation of the CGM.

Clinical course of genetic diseases of the insulin receptor (type A and Rabson-Mendenhall syndromes): a 30-year prospective.

The interaction of insulin with its cell surface receptor is the first step in insulin action and the first identified target of insulin resistance. The insulin resistance in several syndromic forms of extreme insulin resistance has been shown to be caused by mutations in the receptor gene. We studied 8 female patients with the type A form of extreme insulin resistance and 3 patients (2 male and 1 female) with the Rabson-Mendenhall syndrome and followed the natural history of these patients for up to 30 years. The 11 patients ranged in age from 7 to 32 years at presentation. All 11 patients had extreme insulin resistance, acanthosis nigricans, and hyperandrogenism in the female patients, and all but 1 were of normal body weight. This phenotype strongly predicts mutations in the insulin receptor: of the 8 patients studied, 7 were found to have mutations. Similar results from the literature are found in other patients with type A and Rabson-Mendenhall syndromes and leprechaunism. The hyperandrogenic state resulting from hyperinsulinemia and insulin resistance in these patients was extreme: 6 of 8 patients had ovarian surgery to correct the polycystic ovarian syndrome and elevation of serum testosterone. By contrast, a larger group of insulin-resistant patients who were obese with hyperandrogenism, insulin resistance, and acanthosis nigricans (HAIR-AN syndrome) did not have a high probability of mutations in the insulin receptor. The morbidity and mortality of these patients were high: 3 of 11 died, 9 of 11 were diabetic and 1 had impaired glucose tolerance, and 7 of 9 patients had 1 or more severe complication of diabetes. Our literature review revealed that the mortality of leprechaunism is so high that the term leprechaunism should be restricted to infants or young children under 2 years of age. Analogous to patients with the common forms of type 2 diabetes, these patients had a heterogeneous course. In 2 patients who were able to maintain extremely high endogenous insulin production, the fasting blood glucose remained normal even though post-glucose-challenge levels were elevated. Most patients, however, required large doses of exogenous insulin to ameliorate the severe hyperglycemia. Preliminary results of a recent study suggest that recombinant leptin administration may benefit these patients with severe insulin resistance.

Nueva generación de insulinas: glargina U300: Resumen de evidencia clínica / New generation of insulins: glargine U300. Summary of clinical evidence

La diabetes mellitus tipo 2 tiene evolución crónica y progresiva, prevalencia creciente y aún es diagnosticada tardíamente. Esto conlleva mayor incidencia de complicaciones crónicas, con incremento de costos en salud. Existe retraso en el inicio de insulinoterapia por causas relacionadas tanto al paciente como al médico. A pesar de los avances en su tratamiento, una baja proporción de enfermos logra control glucémico adecuado. La alta prevalencia de hipoglucemia en pacientes insulino-tratados, impulsó el desarrollo de una nueva generación de insulinas basales de acción prolongada, mayor estabilidad con menor variabilidad y riesgo de hipoglucemias. El programa EDITION evaluó la eficacia y seguridad de glargina U300 vs. glargina U100 en pacientes con diabetes tipo 1 y 2, en distintas etapas de la enfermedad. Glargina U300 es una nueva formulación de insulina glargina con perfil farmacocinético y farmacodinámico más estable y prolongado que glargina U100. Glargina U300 demostró eficacia y tolerabilidad comparable a glargina U100, con descenso significativo del riesgo de hipoglucemias nocturnas y en 24 horas, aportando mayor flexibilidad en el horario de inyección, con una ventana de 6 horas. Además, no se observó mayor aumento de peso que con glargina U100. El estudio Bright (2018) comparó glargina U300 vs. degludec U100, demostrando mayor beneficio en relación al riesgo de hipoglucemia con Gla-300 durante el período de titulación. Gla-300 es una insulina basal de última generación, disponible para mejorar el control metabólico, con menor riesgo de hipoglucemia.

Type 2 diabetes is a chronic, progressive disease with increasing prevalence and still late diagnostic. This leads to an increase in the incidence of chronic complications, with signifi cantly increasing health costs. There is also a delay in the onset of insulin therapy in patients with type 2 diabetes for causes related to both patients and physicians. Despite advances in treatment, a low proportion of patients achieve adequate glycemic control. The high hypoglycemia prevalence, consequence of insulin, has led to the development of a new generation long-acting basal insulins to achieve a more stable and prolonged action profile, reducing the variability and risk of hypoglycemia. The EDITION program evaluated the efficacy and safety of glargine U300 compared to glargine U100 in patients with type 1 and 2 diabetes at different stages of the disease. Gla-300 is a new formulation of insulin glargine which has a more stable and prolonged pharmacokinetic and pharmacodynamic profile. Gla-300 demonstrated efficacy and tolerability comparable to glargine U100, with a significant decrease in the risk of hypoglycemia, at night and in 24 hours, providing greater flexibility in the injection schedule, with a window of 6 hours. No increase in weight was observed compared to glargine U100. Bright study (2018) compared glargine U300 vs. degludec U100, demonstrating greater benefit in relation to the risk of hypoglycemia with Gla-300 during titration period. Gla-300 is a last-generation basal insulin, available to improve metabolic control, with a lower risk of hypoglycemia.