Abstract Introduction Glycemic control is important to avoid diabetes complications in individuals with cancer. There is no evidence for HbA1c and fructosamine as reliable biomarkers in these conditions. There are particularities in caring for patients with diabetes and cancer that can alter these biomarkers. Objective The aim of this study was to evaluate HbA1c and fructosamine as glycemic biomarkers in people with type 2 diabetes and cancer, undergoing clinical or surgical oncological treatment. Methods The authors conducted a single-center, retrospective analysis with people who have cancer and diabetes. Comparison of glycemic biomarkers (HbA1c, fructosamine, and Self-Monitoring of Blood Glucose [SMBG]) was performed including evaluation in individuals undergoing chemotherapy, using glucocorticoids, with anemia, hypoproteinemia or with reduced estimated Glomerular Filtration Rate (eGFR). Results There was a strong positive correlation between fructosamine and HbA1c (n = 318, r= 0.66, p < 0.001) in people with diabetes and cancer even in those under chemotherapy (n = 101, r= 0.61, p < 0.001) or using glucocorticoids (n = 96, r= 0.67, p<0.001). There was a strong correlation between HbA1c and fructosamine in subjects with anemia (n = 111, r= 0.66, p < 0.001), hypoproteinemia (n = 54, r= 0.67, p < 0.001), or with eGFR ≥ 60 mL/min/1.73 m2 (n = 189, r= 0.70, p < 0.001), and moderate correlation with hypoalbuminemia (n = 21, r= 0.54, p = 0.001) and with reduced eGFR (n = 67, r= 0.57, p < 0.001). The correlations between fructosamine and HbA1c with SMBG were moderate (n = 164, r= 0.49, p < 0.001; n = 111, r= 0.55, p < 0.001, respectively), strong in subjects undergoing chemotherapy, with hypoalbuminemia or hypoproteinemia, and at least moderate, if eGFR < 60 mL/min/1.73 m2 or with anemia. Conclusions Fructosamine and HbA1c can be used as glycemic biomarkers in people with diabetes and cancer, even in those with anemia, hypoproteinemia, or undergoing chemotherapy. HbAc HbA c conditions treatment singlecenter, singlecenter single center, center single-center HbA1c, (HbA1c SelfMonitoring Self Monitoring [SMBG] eGFR. . (eGFR) 318 r 066 0 66 0.66 0.001 0001 001 101 061 61 0.61 96 067 67 0.67 p<0.001. p0001 p<0.001 p<0.001) 111 , 54 6 mLmin173 mLmin mL min 1 73 mL/min/1.7 m 189 070 70 0.70 21 054 0.54 057 57 0.57 0.001. 164 049 49 0.49 055 55 0.55 respectively, respectively respectively) [SMBG (eGFR 31 06 0.6 0.00 000 00 10 9 p000 p<0.00 11 5 mLmin17 7 mL/min/1. 18 07 0.7 05 0.5 16 04 4 0.4 3 0. 0.0 p00 p<0.0 mLmin1 mL/min/1 p0 p<0. mL/min/ p<0 mL/min p<

ABSTRACT Objective: The aim of this study was to investigate the factors associated with hypoglycemia and severe hypoglycemia (SH) in individuals with type 1 diabetes mellitus (T1D) in Brazil. Materials and methods: This multicenter, cross-sectional study was conducted between August 2011 and August 2014 across 10 Brazilian cities. The data were obtained from 1,760 individuals with T1D. Sociodemographic and clinical characteristics related to hypoglycemic events in the previous 4 weeks were evaluated. Results: Of 1,760 individuals evaluated, 1,319 (74.9%) reported at least one episode of hypoglycemia in the previous 4 weeks. The main factors associated with hypoglycemia were lower hemoglobin A1c (HbA1c) level, better adherence to self-monitoring of blood glucose (SMBG), and higher education level. Episodes of SH were reported by 251 (19%) individuals who, compared with subjects with nonsevere hypoglycemia, received lower doses of prandial insulin and higher doses of basal insulin, in addition to reporting less frequent use of long-acting basal insulin analogs. The percentage of SH episodes was evenly distributed across all ranges of HbA1c levels, and there were no correlations between the mean number of nonsevere or severe hypoglycemic events and HbA1c values. Higher alcohol consumption and more frequent hospitalizations were independently associated with SH. Conclusion: Although individuals presenting with hypoglycemia had lower HbA1c values than those not presenting hypoglycemia, there were no correlations between the number of nonsevere hypoglycemia or SH and HbA1c values. Also, the frequency of SH was evenly distributed across all ranges of HbA1c values. Better adherence to SMBG and higher education level were associated with hypoglycemia, while alcohol consumption, higher doses of basal insulin, and more frequent hospitalizations in the previous year were associated with SH.

ABSTRACT Objective: We assessed metrics related to inpatient glycemic control using InsulinAPP, an application available for free in Brazil, on the hospitalist-managed ward of our hospital. Subjects and methods: We performed a retrospective study of patients with type 2 diabetes (T2D) admitted from November 2018 to October 2019. InsulinAPP recommends NPH and regular insulins three times a day, in bolus-correction or basal-bolus schemes. Parameters that included BG within range of 70-180 mg/dL, insulin treatment regimen and frequency of hypoglycemia were evaluated. Results: A total of 147 T2D individuals (23% medicine and 77% surgery) were included (mean age 62.3 ± 12.7 years, HbA1c: 8.3 ± 3.0%). The initial insulin regimen was 50% bolus-correction, 47% basal-bolus and 3% with sliding scale insulin. During hospitalization, 71% patients required a bolus-basal regimen. In the first 10 days of the protocol, 71% BG measurements were between 70-180 mg/dL and 26% patients experienced one or more episodes of hypoglycemia < 70 mg/dL, and 5% with BG < 54 mg/dL. Conclusion: The results of this retrospective study indicate the InsulinAPP application using human insulin formulations was effective and safe for the management of hyperglycemia on a hospitalist-managed ward, with more than 70% BG measurements within the therapeutic range and a low rate of hypoglycemia.

ABSTRACT Objective To analyze interstitial glucose behavior during glucocorticoid use in non-diabetic patients receiving chemotherapy for hematologic malignancies. Methods Prospective pilot study carried out to assess interstitial glucose levels in 15 non-diabetic individuals with hematologic malignancies who received glucocorticoids in combination with chemotherapy. The FreeStyle Libre flash monitoring system (Abbott Diabetes Care) was used for up to 14 days to measure interstitial glucose. Results Median age and body mass index were 53 (42-61) years and 25 (23-28) kg/m2 respectively. Interstitial glucose levels >180mg/dL lasting at least one hour were detected in 60% of participants. Interstitial glucose profile parameters (median and peak interstitial glucose levels and percentage of time during which interstitial glucose levels were >180mg/dL) were significantly (p<0.01) higher during glucocorticoid use (115mg/dL, 218mg/dL and 10% respectively) than after glucocorticoid discontinuation (97mg/dL, 137mg/dL and 0% respectively). Mean interstitial glucose levels increased in the afternoon and at night during glucocorticoid use. Conclusion This pilot study was the first to evaluate interstitial glucose levels in non-diabetic individuals using glucocorticoids in treatment of hematologic cancer. Glucocorticoid use during chemotherapy significantly increases interstitial glucose levels in these patients.

Em decorrência do hiperinsulinismo endógeno (HHE), a hipoglicemia é diagnosticada em um indivíduo sintomático com níveis baixos de glicose plasmática, concomitante a valores elevados de insulina plasmática e peptídeo-C. Entre as causas de HHE, estão as doenças das células-b das ilhotas pancreáticas, o uso de secretagogos e a hipoglicemia autoimune. Neste artigo de revisão, estudamos 24 pacientes com hipoglicemia decorrente de hiperinsulinismo endógeno com a finalidade de descrever os aspectos de diagnóstico e tratamento. Nosso estudo mostrou que, após a realização do teste de jejum de 12h (minijejum) em três dias diferentes, todos os pacientes preencheram os critérios diagnósticos de HHE. Adicionalmente, encontramos que 11 dos 12 pacientes (91,7%) que realizaram o teste do glucagon apresentaram níveis de glicose no tempo 120 minutos menores que 50 mg/dL e inferiores ao valor basal. O teste do minijejum (3 amostras) e o teste do glucagon poderiam ser úteis para evitar a realização do jejum prolongado no diagnóstico do hiperinsulinismo endógeno.

Hypoglycemia due to endogenous hyperinsulinism (EH) is diagnosed in a symptomatic patient with low levels of plasma glucose concomitant with elevated plasma insulin and C-peptide. Causes of EH are pancreatic islet-cells disease, use of insulin secretagogues, and autoimmune hypoglycemia. In this review, the authors studied 24 patients with hypoglycemia due to endogenous hyperinsulinism in order to describe aspects of diagnosis and treatment. Our study demonstrated that after 12 hours of fasting (mini-fasting test; at least three samples), all patients presented the diagnostic criteria for EH. Additionally, we found that 11 of 12 patients (91.7%) who underwent glucagon test achieved glucose levels less than 50 mg/dL and below baseline after 120 minutes. Mini-fasting (3 samples) and glucagon test may be useful to prevent prolonged fasting test to clarify the diagnosis of endogenous hyperinsulinism.

INTRODUÇÃO: O CGMS (sigla do inglês continuous glucose monitoring system) é um instrumento valioso no controle glicêmico e utiliza uma calibração por meio de 3 ou 4 medidas de glicemia capilar inseridas pelo paciente em cada dia do exame. OBJETIVO: Avaliar a interferência da calibração durante a madrugada na acurácia do sistema. MÉTODOS: Os dados das monitorizações foram divididos retrospectivamente em dois grupos: com (Grupo A) ou sem (Grupo B) a calibração da madrugada (entre 1:00 e 5:00 AM). A acurácia do método foi mostrada pela diferença relativa absoluta (DRA%). RESULTADOS: Trinta e quarto dados de monitorização foram avaliados em um total de 112 noites. Um total de 289 leituras pareadas foi analisado - 195 no Grupo A e 94 no Grupo B. Não foi encontrada diferença em DRA% em nenhum período do dia quando adicionada a calibração durante a madrugada. CONCLUSÕES: Esses dados sugerem que a calibração da madrugada não altera a acurácia do método.

INTRODUCTION: Continuous glucose monitoring system is a valuable instrument to measure glycemic control, which uses a retrospective calibration based upon 3 to 4 capillary glucose meter values inserted by the patient each day. OBJECTIVE: We evaluated the interference of calibration during the dawn period in the system accuracy. METHODS: The monitoring data were retrospectively divided into two groups: with (Group A) or without (Group B) the dawn period calibration (between 1:00 and 5:00 AM). Accuracy of the method was expressed by relative absolute difference. RESULTS: Thirty-four continuous glucose monitoring data were evaluated comprising a total of 112 nights. A total of 289 paired readings were analyzed - 195 in Group A and 94 in Group B. We did not find a difference in relative absolute difference (RAD%) in any analyzed period of day by adding dawn calibration. CONCLUSIONS: These data suggest that dawn calibration does not alter accuracy of method.

Este estudo avaliou a eficácia do método de ensino teórico e prático sobre diabetes e a atitude de profissionais médicos quanto à realização de controle glicêmico intensivo. Participaram de um curso de imersão em diabetes, com dois dias de duração, 48 médicos-residentes de clínica médica ou endocrinologia. Os participantes receberam treinamento de monitorização de glicemia capilar, técnicas de aplicação de insulina e contagem de carboidratos, sendo orientados a se portarem como diabéticos e a seguir prescrição médica individual. Foram avaliados através de questionários. No questionário de conhecimentos, observou-se um aumento significante de 12% no índice de acertos entre o início e o final do curso (61,2% e 73,2%, respectivamente, com p < 0,0001). Antes do curso, 70,8% dos participantes diziam ter dificuldades na contagem de carboidratos e 89,6%, na automonitorização glicêmica. Após a experiência prática, 82,9% dos participantes encontraram dificuldades na realização de contagem de carboidratos e 80,8%, na automonitorização; 40,4% fizeram uso de todas as medicações prescritas e 36,1% monitorizaram todas as glicemias. Os resultados deste estudo mostram que esse tipo de curso é eficaz para a aquisição de conhecimentos e contribui com a sensibilização do profissional médico quanto às dificuldades cotidianas enfrentadas pelo portador de diabetes melito na aderência às recomendações.

This study evaluated the effectiveness of theoretical and practical teaching method in diabetes and doctors' position about feasibility of intensive blood glucose control. Forty-eight internal medicine or endocrinology residents participated in a two-day diabetes immersion course. The participants received training on self-blood glucose monitoring, techniques of insulin administration and carbohydrate counting. They were also instructed to behave as patients with diabetes and to follow individual medical prescription. They were assessed through questionnaires. In knowledge assessment, a significant increase of 12% was observed between the beginning and the end of the course (61.2% and 73.2%, respectively, with p < 0.0001). Before the course, 70.8% and 89.6% of the participants believed there were complications in performing carbohydrate counting and blood glucose monitoring, respectively. After the experience, 82.9% of them had difficulties in carbohydrate counting and 80.8% in self-monitoring; 40.4% took all medications prescribed and 36.1% monitored blood glucose correctly. These results show that the methodology of this course is an effective way to disseminate knowledge and that it contributes to doctors becoming more sensitive to daily problems faced by patients with diabetes melito concerning the acceptance of medical recommendations.

Os autores analisam a resistência à insulina, a síndrome metabólica e a disfunção endotelial como consequência de um antecedente comum, a inflamação de baixo nível, o que mostra que a obesidade é um estado inflamatório cronicamente ativado do tecido adiposo. Discute-se, aqui, a sinalização inflamatória de acordo com a localização do tecido adiposo subcutâneo ou visceral.

The authors analyze insulin resistance, the metabolic syndrome and endothelial dysfunction as consequence of a common antecedent, a low grade inflammation, indicating that in obesity there is a chronically activated inflammatory state of the adipose tissue. Furthermore, the inflammatory signaling is discussed according to the adipose tissue depot, visceral or subcutaneous.

A doença de Cushing é rara em crianças e sua ocorrência em gêmeos é ainda mais rara. O presente estudo relata a ocorrência de gêmeas idênticas discordantes quanto à doença de Cushing. Uma das gêmeas, desenvolveu síndrome de Cushing aos 10 anos de idade. Sua investigação demonstrou cortisol urinário elevado, ACTH sérico elevado e testes de supressão com dexametasona compatíveis com doença de Cushing. A RMN mostrou macroadenoma hipofisário que foi operado por via transesfenoidal. O estudo imuno-histoquímico confirmou a presença de células produtoras de ACTH. A paciente entrou em remissão clínica e laboratorial desde a cirurgia. Após o desaparecimento dos estigmas do Cushing, a paciente reiniciou ganho estatural, mas permanece menor que sua irmã gêmea. Esta última permanece saudável 4 anos após o início da doença de sua irmã. Este é o terceiro caso do gênero relatado na literatura. Estes achados sugerem que fatores não genéticos estão envolvidos na gênese da doença de Cushing.

Cushing's disease is rare in children and its ocurrence in identical twins is extremely rare. This paper reports on identical twins discordant for Cushing's disease. One of them first presented with a cushingoid phenotype by the age of 10. Her evaluation showed an increased urinary free-cortisol and serum ACTH. Her pattern in the dexametazone supression tests was compatible with Cushing's disease. MRI disclosed a pituitary macroadenoma which was removed by the transesphenoidal approach. Immunohistochemical studies of the tumor showed the presence of ACTH-producing cells. The patient went into clinical and laboratorial remission after surgery. She re-started to grow after the disappearance of the Cushing's phenotype but she is still shorter than her healthy sister. The latter remains disease-free 4 years after her sister's diagnosis. This represents the third such case reported in the literature. Our findings suggest that acquired factors may be responsible for the genesis of Cushing's disease.

Os autores apresentam uma definição de resistência à insulina e discutem os métodos diagnósticos desde o padrão-ouro - o "clamp" euglicêmico hiperinsulinêmico -, passando pela prova de supressão da insulina, a infusão contínua de glicose, a prova de tolerância à glicose endovenosa com um modelo matemático mínimo, até o teste de tolerância à insulina. Analisam também a glicemia e insulina basais e após sobrecarga oral de glicose. Finalmente mostram fatores que influenciam a ação da insulina, como: peso corporal, condicionamento físico, pêso ao nascimento, tipo de fibra muscular predominante, hormônios, densidade capilar e fluxo no músculo esquelético, dieta, idade e hereditariedade.

The authors define insulin resistance and discuss the diagnostic methods from the "gold-standard" - the euglycemic hyperinsulinemic clamp -, going through the insulin suppression test, the continuous glucose infusion, the intravenous glucose tolerance test with the minimal mathematical model, to the insulin tolerance test. Fasting and post-oral glucose load levels of glucose and insulin are also evaluated. Finally, factors influencing insulin action, as body weight, fitness, weight at birth, type of predominant muscle fibers, hormones, capillary density and flow through the skeletal muscle, diet, age and heredity, are indicated.

Apoplexia pituitária aguda é fenômeno relativamente raro, mesmo em macroadenomas. No entanto, a presença de áreas necro-hemorrágicas intratumorais nestes tumores que não se relacionam a qualquer sintomatologia aguda parece ser bem mais frequente do que se imaginava na era da tomografia. Com o advento da ressonância magnética estas áreas podem ser facilmente diagnosticadas pré-operatoriamente. Dentre os 40 últimos macroadenomas operados e examinados com RMN, 10 possuíam áreas apopléticas subclínicas em seu interior. Sete destes tumores eram não secretores, 2 secretores de GH e um de prolactina. O quadro clínico incluiu, além daqueles correspondentes à eventual secreção endócrina, perda visual progressiva (sem história de piora abrupta ou rápida) (n=8) e cefaléia (n=3). Após a remoção cirúrgica destes tumores e descompressão do aparato óptico, obtivemos melhora visual em 6 pacientes e em 2 a visão permaneceu inalterada. A cefaléia desapareceu em 2 casos. A presença de áreas apopléticas nestes macrotumores bem como sua ausência em séries de microtumores relatadas na literatura sugere que se relacionam mais ao tamanho do tumor do que ao seu caráter secretor ou não, o que é compatível com a provável natureza (insuficiência vascular) da apoplexia subclínica nesses casos.

Acute pituitary apoplexy is a rare event, even in patients with pituitary macroadenomas. On the other hand, the presence of necrotic/hemorrhagic areas, especially in macroadenomas, seems to be more common than earlier reported in the CT period. After the introduction of MR in the presurgical workup of these patients, these apopleptic areas have been more easily diagnosed preoperatively. Forty consecutive patients with pituitary macroadenomas were studied with high-resolution 1.5 T T1 coronal, sagittal and axial slices over the sellar region. Special attention was paid in the detection of necrotic, cystic and hemorrhagic areas within these tumors. Ten patients had hemorrhagic/necrotic areas within their tumors, without any sign or symptom of acute apoplexy. These areas varied from small (2 mm) to very large (30 mm) ones. Seven patients had non-secreting tumors, 2 GH and 1 prolactin secreting tumors, which is the same profile of secretory pattern for the whole series (40 patients). The clinical picture included (other than that caused by endocrine secretion) slowly progressive (but not acute) visual loss (n=8) and headache (n=3). After surgical decompression of the surrounding structures and visual apparatus, which was facilitated by the presence of the necrotic areas, there was visual improvement in 6 patients and headache resolution in 2. The presence of asymptomatic apopleptic areas in these macroadenomas and their absence in microadenomas as can be seen in the literature suggest that they are related more to the size of the tumor than to its endocrine secretion pattern. This is in agreement with a vascular insufficiency hypothesis in the pathogenesis of these lesions.

A apoplexia pituitária é evento raro e a ocorrência de remissão endócrina em pacientes portadores de tumores secretores é ainda mais incomum. O presente estudo relata os casos de dois pacientes portadores de macroadenomas (um com doença de Cushing e outro com acromegalia) nos quais houve remissão endócrina após apoplexia tumoral. A primeira paciente era portadora de doença de Cushing e teve episódio ictal espontâneo de cefaléia e vômitos, após o qual iniciou remissão endócrina. Como houvesse persistência de imagem de macroadenoma à ressonância magnética, a paciente foi submetida a cirurgia transesfenoidal, sendo encontrado apenas cisto hemorrágico hipertensivo, sem sinais de tumor. O segundo paciente apresentava acromegalia e enquanto realizava um teste de LHRH teve evento agudo de cefaléia e vômitos, sem perda visual e instalação de diabetes insipidus. A tomografia computadorizada de sela túrcica mostrou sinais de sangue. Como não houve quadro visual agudo, o paciente foi seguido com exames de imagens seriadas, que demonstraram o desaparecimento completo da lesão e o aparecimento de sela vazia. A avaliação endócrina mostrou remissão da acromegalia. Tendo em vista a tendência à recidiva já documentada na literatura, esses pacientes devem continuar em seguimento a longo prazo.

Pituitary apoplexy is rare and endocrine remission in patients with apopletic secreting pituitary adenomas is even rarer. This study reports on two patients with pituitary macroadenomas (one with Cushing's disease and the other with acromegaly) in whom endocrine remission occurred after apoplexy. The first patient had Cushing's disease and had an ictus of headache and vomiting after which she started a progressive remission of hypercortisolism. A post-apoplexy MRI disclosed persistence of a sellar and supra-sellar mass. She was submitted to transesphenoidal surgery. An hypertensive hemorhagic cyst was found with no tumor. The second patient had acromegaly. While performing a LHRH-stimulation test he had an ictus of headache, vomiting, no visual loss and appearance of diabetes insipidus. A CT scan disclosed an intrasellar hematoma. Despite the size of the tumor and since there was no visual impairment, this patient was followed up without surgery. Imaging follow-up showed a progressive shrinkage and disappearance of the mass, which was corroborated by endocrine remission. A high rate of recurrence is reported in such patients in the literature. Both patients are being currently followed-up on a long-term basis.

O critério imagenológico clássico para diagnóstico de invasão de seio cavernoso é a presença de tumor lateralmente à carótida em cortes coronais. Estudamos 17 pacientes com macroadenomas hipofisários com ressonância compátivel a invasão de seio cavernoso e que tiveram esta invasão confirmada cirurgicamente. Somente 8 destes pacientes possuíam tumor lateralmente à carótida (critério clássico). Treze pacientes possuíam tumor localizado entre as porções intracavernosas da carótida e em todos havia ruptura da captação anelar de contraste no seio cavernoso. Dez pacientes possuíam abertura dos folhetos posteriores do seio cavernoso. Todos os pacientes foram tratados por via transesfenoidal. Somente um caso obteve cura endocrinológica. Somente 3 pacientes portadores de algum destes sinais imagenológicos foram identificados em uma série de cerca de 250 casos e não possuíam invasão de seio cavernoso. Os critérios acima parecem adequadamente permitir prever a invasão do seio. Este diagnóstico é relevante já que a maioria dos pacientes com invasão de seio cavernoso acaba realizando terapia complementar.

The classical imaging gold-standard for this diagnosis is the presence of tumor lateral to the carotid artery. Seventeen patients with pituitary macroadenomas with intraoperative confirmation of cavernous sinus invasion were studied with MRI. Only 8 patients had tumor lateral to the carotid artery; 13 had tumor within the carotid syphon and all lacked the ring enhancement of the medial wall of the cavernous sinus. In 10 patients, widening of the posterior double leaflets of the cavernous sinus could be. All patients were operated by the transesphenoidal route. Only one patient was cured by surgery alone. Only 3 patients disclosing the above mentioned MRI features were identified in a series of 250 patients and did not have cavernous sinus invasion. The present criteria proved to be useful in the pre-operative diagnosis of cavenous sinus invasion and patients' counselling. Pre-operative diagnosis of cavernous sinus invasion of pituitary tumors has a great impact in the management of such patients.