Is biochemical hypoglycemia necessary during an insulin tolerance test?

ABSTRACT Objective The insulin tolerance test (ITT) has been accepted as the gold standard test for assessing the integrity of the growth hormone (GH) - insulin-like growth factor (IGF-1) axis and the hypothalamic-pituitary-adrenal (HPA) axis. The goal of the test is to achieve clinical and biochemical hypoglycemia at a blood glucose level ≤ 40 mg/dL to effectively and correctly assess the HPA and GH-IGF-1 axes. In this study, the GH and cortisol responses of patients who achieved and failed to achieve biochemical hypoglycemia during an ITT were compared. Subjects and methods One hundred thirty-five patients with pituitary disorders were included in the study. Samples for blood glucose levels were obtained after clear symptoms of clinical hypoglycemia developed. The patients were enrolled in the hypoglycemic and nonhypoglycemic groups according to whether their plasma glucose level ≤ 40 mg/dL or > 40 mg/dL during an ITT, and the groups were compared in terms of their GH and cortisol responses. Results The mean age, body mass index and waist circumference of the two patient groups were found to be similar. The mean blood glucose level was significantly lower in the hypoglycemic group than in the nonhypoglycemic group (19.3 and 52.0 mg/dL, respectively). When the two groups were compared in terms of peak cortisol and GH responses, no statistically significant differences were found. Conclusion The data presented suggest that clinically symptomatic hypoglycemia is as effective as biochemically confirmed hypoglycemia during an ITT. Arch Endocrinol Metab. 2020;64(1):82-8

Performance during a strenuous swimming session is associated with high blood lactate: pyruvate ratio and hypoglycemia in fasted rats

The aim of this study was to investigate the effect of lactatemia elevation and glycemia reduction on strenuous swimming performance in fasted rats. Three rats were placed in a swimming tank at the same time. The first rat was removed immediately (control group) and the remaining ones were submitted to a strenuous swimming session. After the second rat was exhausted (Exh group), the third one was immediately removed from the water (Exe group). According to the period of time required for exhaustion, the rats were divided into four groups: low performance (3-7 min), low-intermediary performance (8-12 min), high-intermediary performance (13-17 min), and high performance (18-22 min). All rats were removed from the swimming tanks and immediately killed by decapitation for blood collection or anesthetized for liver perfusion experiments. Blood glucose, lactate, and pyruvate concentrations, blood lactate/pyruvate ratio, and liver lactate uptake and its conversion to glucose were evaluated. Exhaustion in low and low-intermediary performance were better associated with higher lactate/pyruvate ratio. On the other hand, exhaustion in high-intermediary and high performance was better associated with hypoglycemia. Lactate uptake and glucose production from lactate in livers from the Exe and Exh groups were maintained. We concluded that there is a time sequence in the participation of lactate/pyruvate ratio and hypoglycemia in performance during an acute strenuous swimming section in fasted rats. The liver had an important participation in preventing hyperlactatemia and hypoglycemia during swimming through lactate uptake and its conversion to glucose.

Allostatic load and canine companionship: a comparative study using biomarkers in older adults / Carga alostática e companhia canina: um estudo comparativo utilizando biomarcadores em idosos / Carga alostática y compañía canina: un estudio comparativo mediante biomarcadores en adultos mayores

ABSTRACT Objective: to compare the biomarkers and the allostatic load levels in a sample of older persons with and without canine companionship. Method: descriptive and comparative study. Data were collected using a sociodemographic questionnaire and a fasting blood sample. The allostatic load comprised 11 biomarkers that are primary and secondary stress mediators, which arise from the following systems: neuroendocrine, immune, metabolic, cardiovascular and anthropometric. Results: a significant difference was found in two biomarkers: cortisol (t= -3.091, df=104, p=0.003) and total cholesterol (t= -2.566, df=104, p=0.012), in the allostatic load levels between older adults with and without a canine companionship (U= 1714.00, Z= 2.01, p=0.044). By associating the allostatic load level with the canine companionship, there was a higher frequency of older adults with low allostatic load among those who have canine companion, compared with those who do not have canine companionship. (χ2= 3.69, df=1, p= 0.043). Conclusion: canine companionship influences health in a positive way, as the allostatic load is lower in older adults who have a dog as companion, in addition to presenting lower levels of cortisol and total cholesterol.

RESUMO Objetivo: comparar os biomarcadores e o nível de carga alostática em uma amostra de idosos com e sem companhia canina. Método: estudo descritivo e comparativo. Os dados foram coletados por meio de uma ficha sociodemográfica e uma amostra de sangue em jejum. A carga alostática incluiu 11 biomarcadores que são mediadores primários e secundários de estresse, os quais são resultantes dos sistemas: neuroendócrino, imune, metabólico, cardiovascular e antropométrico. Resultados: houve diferença significativa em dois biomarcadores: cortisol (t= -3,091; gl=104; p=0,003) e colesterol total (t= -2,566; gl=104; p=0,012), no nível de carga alostática entre os idosos com e sem companhia canina (U= 1714,00; Z= 2,01; p= 0,044). Ao associar o nível de carga alostática com a companhia canina, houve uma maior frequência de idosos com baixa carga alostática naqueles que têm companhia canina, em comparação com aqueles que não têm a companhia canina (χ2= 3,69; gl=1; p=0,043). Conclusão: a companhia canina interfere na saúde de maneira positiva, pois a carga alostática dos idosos que têm um cão como companhia é menor, além de apresentarem uma concentração menor de cortisol e de colesterol total.

RESUMEN Objetivo: comparar los biomarcadores y el nivel de carga alostática en una muestra de adultos mayores con y sin acompañamiento canino. Método: estudio descriptivo, comparativo. Los datos se colectaron mediante una ficha sociodemográfica y una muestra de sangre en ayuno. La carga alostática incluyó 11 biomarcadores que son mediadores primarios y secundarios del estrés, los cuales provienen de los sistemas: neuroendocrino, inmune, metabólico, cardiovascular y antropométrico. Resultados: hubo diferencia significativa en dos biomarcadores: cortisol (t=-3.091, gl=104, p=0.003) y colesterol total (t=-2.566, gl=104, p=0.012), en el nivel de carga alostática entre los adultos mayores con y sin compañía canina (U=1714.00, Z=2.01, p=0.044). Al asociar el nivel de carga alostática con la compañía canina, existió mayor frecuencia de adultos mayores con carga alostática baja en quienes son acompañados por un canino, comparado con aquellos que no tienen acompañamiento canino (χ2=3.69, gl=1, p=0.043). Conclusión: el acompañamiento canino interviene en la salud de forma positiva, ya que es menor la carga alostática de los adultos mayores que tienen un perro como compañía, asimismo, presentan menor concentración de cortisol y colesterol total.

Correlation between parameters of self-monitoring of blood glucose and the perception of health-related quality of life in patients with type 1 diabetes mellitus

ABSTRACT Objective The aim of this study was to evaluate how different parameters of short-term glycemic control would correlate with the perception of health-related quality of life (HRQoL) in patients with type 1 diabetes mellitus (T1D). Subjects and methods A total of 50 T1D patients aged 18 to 50 years were evaluated with the questionnaires Problem Areas in Diabetes (PAID) scale and Diabetes Quality of Life (DQOL) measure after 30 days of self-monitoring of blood glucose (SMBG). Glycemic control was evaluated using glycated hemoglobin (HbA1c), mean glucose levels (MGL) in the prior month's data from SMBG (Accu-Check 360o), number of hypoglycemic episodes (< 70 mg/dL and < 50 mg/dL), and glycemic variability (GV). Results PAID correlated positively with MGL (r = 0.52; p < 0.001) and HbA1c (r = 0.36; p < 0.0097), but not with GV (r = 0.17; p = 0.23) or number of hypoglycemic episodes (r = 0.15; p = 0.17 for glucose < 70 mg/dL and r = 0.02; p = 0.85 for glucose < 50 mg/dL). After multiple linear regression, only MGL remained independently related to PAID scores. DQOL scores had a positive correlation with MGL (r = 0.45; p = 0.001), but not with HbA1c (r = 0.23; p = 0.09), GV (r = 0.20; p = 0.16), or number of hypoglycemic episodes (r = 0.06 p = 0.68). Conclusion In T1D patients, MGL, but not HbA1c or number hypoglycemic episodes, was the glycemic control parameter that best correlated with short-term perception of HRQoL.

Risk factors for unstable blood glucose level: integrative review of the risk factors related to the nursing diagnosis / Risco de glicemia instável: revisão integrativa dos fatores de risco do diagnóstico de enfermagem / Riesgo de nivel de glucemia inestable: revisión integradora de los factores de riesgo del diagnóstico de enfermeira

ABSTRACT Objective: to identify evidence in the literature on the possible risk factors for the risk of unstable blood glucose diagnosis in individuals with type 2 diabetes mellitus, and to compare them with the risk factors described by NANDA International. Method: an integrative literature review guided by the question: what are the risk factors for unstable blood glucose level in people with type 2 diabetes mellitus? Primary studies were included whose outcomes were variations in glycemic levels, published in English, Portuguese or Spanish, in PubMed or CINAHL between 2010 and 2015. Results: altered levels of glycated hemoglobin, body mass index>31 kg/m2, previous history of hypoglycemia, cognitive deficit/dementia, autonomic cardiovascular neuropathy, comorbidities and weight loss corresponded to risk factors described in NANDA International. Other risk factors identified were: advanced age, black skin color, longer length of diabetes diagnosis, daytime sleepiness, macroalbuminuria, genetic polymorphisms, insulin therapy, use of oral antidiabetics, and use of metoclopramide, inadequate physical activity and low fasting glycemia. Conclusions: risk factors for the diagnosis, risk for unstable blood glucose level, for persons with type 2 diabetes mellitus were identified, and 42% of them corresponded to those of NANDA International. These findings may contribute to the practice of clinical nurses in preventing the deleterious effects of glycemic variation.

RESUMO Objetivo: identificar evidências na literatura acerca de possíveis fatores de risco do diagnóstico risco de glicemia instável para pessoas com diabetes mellitus tipo 2 e compará-los com os fatores de risco descritos pela NANDA International . Método: revisão integrativa norteada pela pergunta: quais são os fatores de risco de glicemia instável em pessoas com diabetes mellitus tipo 2? Incluíram-se estudos primários cujos desfechos eram variações nos níveis glicêmicos, publicados em inglês, português ou espanhol no PubMed ou CINAHL entre 2010 e 2015. Resultados: observou-se que alteração nos níveis de hemoglobina glicada, índice de massa corpórea>31 Kg/m2, história prévia de hipoglicemia, déficit cognitivo/demência, neuropatia autonômica cardiovascular, comorbidades e perda de peso correspondiam a fatores de risco descritos pela NANDA International . Outros fatores de risco identificados foram: idade avançada, raça negra, maior tempo de diagnóstico de diabetes, sonolência diurna, macroalbuminúria, polimorfismos genéticos, insulinoterapia, uso de antidiabéticos orais, uso de metoclopramida, atividade física inadequada e glicemia de jejum baixa. Conclusões: identificaram-se fatores de risco do diagnóstico risco de glicemia instável para pessoas com diabetes mellitus tipo 2, dos quais 42% correspondiam àqueles da NANDA International . Esses achados podem contribuir para a prática de enfermeiros clínicos na prevenção dos efeitos deletérios da variação glicêmica.

RESUMEN Objetivo: identificar evidencias en la literatura acerca de posibles factores de riesgo del diagnóstico "riesgo de nivel de glucemia inestable" para personas con diabetes mellitus tipo 2 y compararlos con los factores de riesgo descritos por la NANDA International . Método: revisión integradora orientada por la pregunta: ¿Cuáles son los factores de riesgo de nivel de glucemia inestable en personas con diabetes mellitus tipo 2? Se incluyeron estudios primarios cuyos resultados eran variaciones en los niveles glucémicos, publicados en inglés, portugués o español en el PubMed o CINAHL entre 2010 y 2015. Resultados: se observó que una alteración en los niveles de: hemoglobina glucosilada, índice de masa corporal >31 Kg/m2, historia previa de hipoglucemia, déficit cognitivo/demencia, neuropatía autonómica cardiovascular, comorbilidades y pérdida de peso, correspondían a factores de riesgo descritos por la NANDA International . Otros factores de riesgo identificados fueron: edad avanzada, raza negra, mayor tiempo de diagnóstico de diabetes, somnolencia diurna, macroalbuminuria, polimorfismos genéticos, insulinoterapia, uso de antidiabéticos orales, uso de metoclopramida, actividad física inadecuada y glucemia de ayuno baja. Conclusiones: se identificaron factores de riesgo del diagnóstico riesgo de nivel de glucemia inestable para personas con diabetes mellitus tipo 2, de los cuales 42% correspondían a los de la NANDA International . Esos hallazgos pueden contribuir para la práctica de enfermeros clínicos en la prevención de los efectos deletéreos de la variación glucémica.

Blood levels of pro-inflammatory and anti-inflammatory cytokines during an oral glucose tolerance test in patients with symptoms suggesting reactive hypoglycemia

We evaluated the impact of postprandial glycemia on blood levels of pro-inflammatory and anti-inflammatory cytokines during an oral glucose tolerance test in non-diabetic patients with symptoms suggesting reactive hypoglycemia. Eleven patients with clinical symptoms suggesting reactive hypoglycemia received an oral glucose solution (75 g) Blood was collected at 0 (baseline), 30, 60, 120 and 180 min after glucose ingestion and the plasma concentrations of interferon-α (IFN-α), interferon-γ (IFN-γ), interleukin-1 receptor antagonist (IL-1RA), interleukin 2 (IL-2), interleukin-2 receptor (IL-2R), interleukin 4 (IL-4), interleukin 6 (IL-6), interleukin 8 (IL-8), interleukin 10 (IL-10), interleukin-12 (IL-12), interleukin 13 (IL-13), interleukin 15 (IL-15), interleukin 17 (IL-17), IFN-γ inducible protein 10 (IP-10), monocyte chemotactic protein 1 (MCP1), monokine induced by IFN-γ (MIG), macrophage inflammatory protein-1α (MIP-1α), interleukin-1β (IL-1β), colony stimulating factor (G-CSF), granulocyte-macrophage CSF (GM-CSF), basic fibroblast growth factor (FGF-basic), eotaxin, tumor necrosis factor α (TNFα), epidermal growth factor (EGF), hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), macrophage inflammatory protein-1α (MIP-1α), and 1β (MIP-1β) were evaluated. Overall, glycemic levels increased, reached its maximum at 30 min (phase 1), returned to baseline levels at 120 min (phase 2), followed by a mild hypoglycemia at 180 min (phase 3). During phase 1, cytokine blood levels were maintained. However, we observed a synchronous fall (P<0.05) in the concentrations of pro-inflammatory (IL-15, IL-17, MCP-1) and anti-inflammatory cytokines (FGF-basic, IL-13, IL-1RA) during phase 2. Furthermore, a simultaneous rise (P<0.05) of pro-inflammatory (IL-2, IL-5, IL-17) and anti-inflammatory cytokines (IL-4, IL-1RA, IL-2R, IL-13, FGF-basic) occurred during phase 3. Thus, mild acute hypoglycemia but not a physiological increase of glycemia was associated with increased blood levels of anti-inflammatory and pro-inflammatory cytokines.

Risk of hypoglycemia during hemodialysis in diabetic patients is related to lower pre-dialysis glycemia

Objective To compare the occurrence of hypoglycemia during hemodialysis in chronic kidney disease diabetic patients who present different levels of pre-dialysis glycemia both when using dialysis solutions with and without glucose. Subjects and methods Twenty type 2 diabetic patients in maintenance hemodialysis were submitted to three dialysis sessions (at a 7-day interval each) with dialysis solutions without glucose, with glucose at 55 mg/dL, and at 90 mg/dL subsequently. Blood glucose levels were measured immediately pre-dialysis and at 4 moments during the session, and values under 70 mg/dL were considered as hypoglycemia. Results Average pre-dialysis glycemia was lower in those who presented intra-dialytic hypoglycemia than in those who did not, both in glucose-free (140.4 ± 50.7 vs. 277.7 ± 91.0 mg/dL; p = 0.005; 95%CI: 46.4 to 228.1) and in glucose 55 mg/dL (89.5 ± 10.6 vs. 229.7 ± 105.0 mg/dL; p < 0.05; 95%CI: 9.8 to 270.5). In patients with pre-dialysis glycemia under 140 mg/dL, average intradialytic glycemia was significantly lower than pre-dialysis glycemia only when using glucose-free dialysate (p < 0.0001; 95%CI: 29.9 to 56.0 - t-test). Hypoglycemia during dialysis was observed only when using glucose-free or glucose-poor dialysis solutions. Conclusions The use of glucose-free or glucose-poor dialysis solution presents a high risk of intradialytic hypoglycemia in diabetic renal patients, especially in those with presumed better glycemic control. .

Evaluation of diabetic patients after three month use of continuous subcutaneous insulin infusion, dispensed by a protocolled form at outpatient reference clinic of Taguatinga Regional Hospital

Objective To evaluate the data of continuous subcutaneous insulin infusion protocol (CSII) for diabetics waived by the Health State Secretariat of Distrito Federal (HSSDF) and therapeutic responses three months after the transfer of multiple daily injections regimen for CSII. Subjects and methods Eighty patients (49 female) took part in this experimental study, mean age and disease duration were 27.9 years and 13 years, respectively; 96% patients had type 1 diabetes mellitus. Results The entire sample (ECO) and 3 subgroups (group 1 – A1c decrease, group 2 – A1c stable, and group 3 – A1c increase), stratified according to a ≥ 0.5% change in A1c, were analyzed. Group 1 involved 64% of the patients. The ECO showed a significant A1c decrease: MDI 8.1 ± 1.4% vs. CSII 7.3 ± 0.9%, p < 0.0001 (0.8% difference pro CSII therapy). Group 1 demonstrated an A1c decrease from 8.7% to 7.3% (1.4% difference). Group 2 mean A1c was 7.1%. Rate of hypoglycemia (< 50 mg/dL) decreased 61% in the ECO and 79% in Group 2. Conclusion This study reinforces the safety and efficacy of CSII with a robust A1c reduction and hypoglycemia. The pioneer care HSSDF ambulatory attests to be achievable the free dispensing by Unified Health System (UHS) following a protocol, and this approach results in less wastage to the patient and represents a rational policy of therapy with CSII for UHS. Arch Endocrinol Metab. 2015;59(1):23-8 .

Blood electrolyte disturbances during severe hypoglycemia in Korean patients with type 2 diabetes

BACKGROUND/AIMS: To investigate abnormalities in blood electrolyte levels during severe hypoglycemia in Korean patients with type 2 diabetes mellitus (T2DM) in a clinical setting. METHODS: Blood electrolyte levels in adult T2DM patients during severe hypoglycemia were collected from January 1, 2008 to December 31, 2012. Patients who maintained normal serum creatinine and blood urea nitrogen levels were utilized in the study. Severe hypoglycemia was defined as a condition requiring medical assistance, such as administering carbohydrates when serum glucose levels less than 70 mg/dL were observed, in conjunction with other symptoms of hypoglycemia. RESULTS: A total of 1,068 patients who visited the emergency room with severe hypoglycemia were screened, of which 219 patients were included in this study. The incidence of abnormal levels for any electrolyte was 47%. Hypokalemia ( 100 beats per minute) and severe hypertension (> or = 180/120 mmHg) were 30 mg/dL (range, 14 to 62) and 35 mg/dL (range, 10 to 69; p = 0.04), 18.8% and 7.2% (p = 0.02), and 20.8% and 10.2% (p = 0.05) in the hypokalemia and normokalemia groups, respectively. CONCLUSIONS: During severe hypoglycemia, hypokalemia occurred in 21.9% of T2DM patients and was associated with tachycardia and severe hypertension. Therefore, the results suggest that severe hypoglycemia may increase cardiovascular events in T2DM.

Avoiding or coping with severe hypoglycemia in patients with type 2 diabetes

Hypoglycemia is a major barrier to achieving the glycemic goal in patients with type 2 diabetes. In particular, severe hypoglycemia, which is defined as an event that requires the assistance of another person to actively administer carbohydrates, glucagon, or take other corrective actions, is a serious clinical concern in patients with diabetes. If severe hypoglycemia is not managed promptly, it can be life threatening. Hypoglycemia-associated autonomic failure (HAAF) is the main pathogenic mechanism behind severe hypoglycemia. Defective glucose counter-regulation (altered insulin secretion, glucagon secretion, and an attenuated increase in epinephrine during hypoglycemia) and a lack of awareness regarding hypoglycemia (attenuated sympathoadrenal activity) are common components of HAAF in patients with diabetes. There is considerable evidence that hypoglycemia is an independent risk factor for cardiovascular disease. In addition, hypoglycemia has a significant influence on the quality of life of patients with diabetes. To prevent hypoglycemic events, the setting of glycemic goals should be individualized, particularly in elderly individuals or patients with complicated or advanced type 2 diabetes. Patients at high-risk for the future development of severe hypoglycemia should be selected carefully, and intensive education with reinforcement should be implemented.

Avaliação da frutosamina como parâmetro de controle glicêmico na gestante diabética / Evaluation of fructosamine as a parameter of blood glucose control in diabetic pregnant women

Objetivo Avaliar parâmetros alternativos para monitorar a glicemia em portadoras de diabetes na gestação estudando a relação entre a frutosamina e a automonitoração em gestantes portadoras de diabetes. Materiais e métodos: A frutosamina sérica e os parâmetros da automonitoração nos 14 dias que antecederam a coleta da frutosamina foram avaliados em 47 gestantes portadoras de diabetes. Resultados Setenta e uma determinações de frutosamina e 2.238 glicemias capilares (GCs) foram analisadas. A frutosamina correlacionou-se com o índice de excursões hiperglicêmicas (HBGI) e o desvio-padrão das glicemias (r = 0,28; p = 0,021 e r = 0,26; p = 0,03, respectivamente). A comparação entre as mães dos neonatos com peso adequado ou grandes ao nascer com as genitoras que tiveram neonatos pequenos para a idade gestacional (PIG) revelou que estas tiveram menor média glicêmica (105 vs. 114 e 119 mg/dL), maior índice de excursões hipoglicêmicas (5,8 vs. 1,3 e 0,7) e maior percentual de hipoglicemias (11 vs. 0 e 0%) mesmo com frutosamina dentro dos valores de referência (242 vs. 218 e 213 μmol/l). Conclusão A frutosamina pode ser utilizada como parâmetro auxiliar à automonitoração para avaliação de hiperglicemias e variabilidade glicêmica, entretanto pode subestimar hipoglicemias em gestantes com fetos PIG. .

Objective To evaluate the alternative parameters to monitor glycemia in pregnant women with diabetes studying the relationship between fructosamine testing and self monitoring of blood glucose in pregnant women with diabetes. Materials and methods Serum fructosamine levels and the self monitoring of blood glucose over 14 days before the collection of fructosamine were evaluated in 47 diabetic pregnant women. Results Seventy-one fructosamine levels and 2,238 glucose measurements (CGs) were analysed. Levels of fructosamine correlated with high blood glucose index (HBGI) and the standard deviation of glycemias (r = 0.28; p = 0.021 and r = 0.26; p = 0.03, respectively). The comparison between the mothers of the newborns with appropriated or large birthweight and those who gave birth to small newborns for their gestational age (SGA) showed that the latter had a lower glycemic mean (105 vs. 114 and 119 mg/dL), a higher low blood glucose index (5.8 vs. 1.3 and 0.7) and a higher percentage of hyperglycemias (11 vs. 0 and 0%) even when the fructosamine falls within the reference values (242 vs. 218 and 213 μmol/l). Conclusion The levels of fructosamine can be used as further parameter to aid self monitoring of blood glucose to evaluate hyperglycemias and glycemic variability, however, this can underestimate hypoglycemias in pregnant women carrying small-for-gestational age fetuses. .

Beneficial effects of Ginkgo biloba extract on insulin signaling cascade, dyslipidemia, and body adiposity of diet-induced obese rats

Ginkgo biloba extract (GbE) has been indicated as an efficient medicine for the treatment of diabetes mellitus type 2. It remains unclear if its effects are due to an improvement of the insulin signaling cascade, especially in obese subjects. The aim of the present study was to evaluate the effect of GbE on insulin tolerance, food intake, body adiposity, lipid profile, fasting insulin, and muscle levels of insulin receptor substrate 1 (IRS-1), protein tyrosine phosphatase 1B (PTP-1B), and protein kinase B (Akt), as well as Akt phosphorylation, in diet-induced obese rats. Rats were fed with a high-fat diet (HFD) or a normal fat diet (NFD) for 8 weeks. After that, the HFD group was divided into two groups: rats gavaged with a saline vehicle (HFD+V), and rats gavaged with 500 mg/kg of GbE diluted in the saline vehicle (HFD+Gb). NFD rats were gavaged with the saline vehicle only. At the end of the treatment, the rats were anesthetized, insulin was injected into the portal vein, and after 90s, the gastrocnemius muscle was removed. The quantification of IRS-1, Akt, and Akt phosphorylation was performed using Western blotting. Serum levels of fasting insulin and glucose, triacylglycerols and total cholesterol, and LDL and HDL fractions were measured. An insulin tolerance test was also performed. Ingestion of a hyperlipidic diet promoted loss of insulin sensitivity and also resulted in a significant increase in body adiposity, plasma triacylglycerol, and glucose levels. In addition, GbE treatment significantly reduced food intake and body adiposity while it protected against hyperglycemia and dyslipidemia in diet-induced obesity rats. It also enhanced insulin sensitivity in comparison to HFD+V rats, while it restored insulin-induced Akt phosphorylation, increased IRS-1, and reduced PTP-1B levels in gastrocnemius muscle. The present findings suggest that G. biloba might be efficient in preventing and treating obesity-induced insulin signaling impairment.

Pathomorphological effects of alloxan induced acute hypoglycaemia in rabbits

Alloxan is one of the frequently used beta-cytotoxic agents for the induction of Type-1 diabetes mellitus in animal models and is the drug of choice in rabbits. Its beta-cytotoxic action results in a sudden release of insulin leading to severe hypoglycaemia and even mortality if glucose therapy is not given. In the present investigation the pathological effects of alloxan induced acute hypoglycaemia were studied in rabbits. New Zealand White rabbits, 1-1.5 kg body weight, were administered alloxan@100 mg/kg b.w., as a single intravenous dose. Blood glucose levels were monitored [0 h, 20 min, 1 h, and then hourly up to 5 h] and clinical signs noted. Rabbits dead due to hypoglycaemia were necropsied and histopathology performed. Severe histopathological changes were observed especially in the brain [neuronal degeneration and necrosis], kidneys [nephrosis, nephritis] and liver [hepatosis, hepatitis] and also, other organs. Histopathological observation of beta-cytolysis was suggestive that the drug induced hypoglycaemia is insulin mediated. It was concluded that acute hypoglycaemia causes severe pathological changes and the alloxan induced immediate hypoglycaemia if not managed in time, might exacerbate the pathological effects of hyperglycaemia in the induced diabetic models

Type B insulin-resistance syndrome presenting as autoimmune hypoglycemia, associated with systemic lupus erythematosus and interstitial lung disease

We describe an unusual case of systemic lupus erythematosus with pulmonary manifestations presenting as hypoglycemia due to anti-insulin receptor antibodies. A 38-year-old female suffered an episode of unconsciousness and was admitted to hospital where her blood glucose was found to be 18 mg/dL. During the hypoglycemic episode, her serum insulin level was inappropriately high (2,207.1 pmol/L; normal range, 18 to 173) and C-peptide level was elevated (1.7 nmol/L; normal range, 0.37 to 1.47). Further blood tests revealed the presence of antinuclear antibodies, anti-double-stranded DNA antibodies, and anti-Ro/SSA, anti-La/SSB, anti-ribonucleoprotein, and anti-insulin receptor antibodies. A computed tomography scan of the abdomen, aimed at tumor localization, such as an insulinoma, instead revealed ground-glass opacities in both lower lungs, and no abnormal finding in the abdomen. For a definitive diagnosis of the lung lesion, video-associated thoracoscopic surgery was performed and histopathological findings showed a pattern of fibrotic non-specific interstitial pneumonia.

Influence of Pre-operative Fasting Time on Blood Glucose in Older Patients

PURPOSE: This study was performed to identify changes in blood glucose at preoperative fasting time in surgical patients over 60 yr. METHODS: Data collection was performed from July, 2008 through July, 2009. Participants consisted of 80 nondiabetic surgical patients. Blood glucose was checked from 3 to 5 times. The 5 times were 2-hr fasting on the pre-operative day (T1, n=80), 8 hr (T2, n=80), 10 hr (T3, n=17), 12 hr (T4, n=34) and 14 hr fasting on the day of the operation (T5, n=29). RESULTS: Of the patients, 27.5% had a blood glucose level of less than 79 mg/dL at T2; 17.6% at T3; 32.4% at T4; and 17.2% at T5. Mean blood glucose levels were 93.8 mg/dL at T1; 88.4 mg/dL at T2; 91.7 mg/dL at T3; 87.4 mg/dL at T4: and 94.1 mg/dL at T5. Blood glucose was the lowest at T2 (p60 yr-of-age be observed for hypoglycemia during pre-operative fasting of more than 10 hr and that surgical patients >60 yr-of-age with risks for hypoglycemia be scheduled for operation within 10 hr preoperative fasting.

Hypoglycemia Revisited in the Acute Care Setting

Hypoglycemia is a common finding in both daily clinical practice and acute care settings. The causes of severe hypoglycemia (SH) are multi-factorial and the major etiologies are iatrogenic, infectious diseases with sepsis and tumor or autoimmune diseases. With the advent of aggressive lowering of HbA1c values to achieve optimal glycemic control, patients are at increased risk of hypoglycemic episodes. Iatrogenic hypoglycemia can cause recurrent morbidity, sometime irreversible neurologic complications and even death, and further preclude maintenance of euglycemia over a lifetime of diabetes. Recent studies have shown that hypoglycemia is associated with adverse outcomes in many acute illnesses. In addition, hypoglycemia is associated with increased mortality among elderly and non-diabetic hospitalized patients. Clinicians should have high clinical suspicion of subtle symptoms of hypoglycemia and provide prompt treatment. Clinicians should know that hypoglycemia is associated with considerable adverse outcomes in many acute critical illnesses. In order to reduce hypoglycemia-associated morbidity and mortality, timely health education programs and close monitoring should be applied to those diabetic patients presenting to the Emergency Department with SH. ED disposition strategies should be further validated and justified to achieve balance between the benefits of euglycemia and the risks of SH. We discuss relevant issues regarding hypoglycemia in emergency and critical care settings.

Perfil das mães de neonatos com controle glicêmico nas primeiras horas de vida / Profile of mothers of newborns with blood glucose control in the first hours of life / Perfil de las madres de neonatos con control glucémico en las primeras horas de vida

Alguns fatores maternos associados ao quadro de hipoglicemia neonatal indicam a monitoração dos níveis glicêmicos nas primeiras 24 horas de vida. O estudo objetivou descrever as características sócio-demográficas e obstétricas de mães de neonatos com controle de glicemia capilar nas primeiras 24 horas de vida, internadas em Alojamento Conjunto de um Hospital Amigo da Criança. Estudo descritivo-exploratório que analisou dados de 380 prontuários médicos de mães internadas entre julho e dezembro de 2006, na unidade de Alojamento Conjunto do Hospital Universitário da Universidade de São Paulo. Diabetes gestacional foi verificado em 18 (5,6 por cento) mães; nenhuma tratou com hipoglicemiante oral; 53 (16,2 por cento) tiveram hipertensão arterial na gestação, e 17 (32,1 por cento) fizeram uso de anti-hipertensivo; 215 (56,6 por cento) receberam soro glicosado, 5 por cento no trabalho de parto e parto. Estudos correlacionais analisando variáveis maternas e ocorrência de hipoglicemia neonatal devem ser realizados, objetivando identificar os fatores preditores desta morbidade neonatal.

Some maternal factors associated with neonatal hypoglycemia justify monitoring blood glucose levels in the first 24 hours of life. The objective of this study was to describe the socio-demographic and obstetric characteristics of mothers to newborns undergoing capillary blood glucose control in the first 24 hours of life, hospitalized in a rooming-in maternity ward of a Baby Friendly Hospital. This is a descriptive exploratory study which involved the analysis of data from 380 medical records of mothers hospitalized from July to December, 2006 at the maternity ward of the University of São Paulo Teaching Hospital. It was found that 18 (5.6 percent) mothers developed gestational diabetes, none of them were treated with oral hypoglycemic agents, 53 (16.2 percent) had hypertension during pregnancy and 17 (32.1 percent) used anti-hypertensive medication, 215 (56.6 percent) received glucose 5 percent continuous infusion during labor and delivery. Correlation studies linking maternal variables and neonatal hypoglycemia are needed to identify the predicting factors of this neonatal morbidity.

Algunos factores maternos asociados al cuadro de hipoglucemia neonatal indican la monitorización de los niveles de glucemia en las primeras 24 horas de vida. El estudio tuvo como objetivo describir las características sociodemográficas y obstétricas de madres de neonatos con control de glucemia capilar en las primeras 24 horas de vida, internadas en Alojamiento Conjunto de un Hospital Amigo de la Niñez. Estudio de tipo descriptivo exploratorio que analizó datos de 380 historias clínicas de madres internadas entre julio y diciembre de 2006 en la Unidad de Alojamiento Conjunto del Hospital Universitario de la Universidad de San Pablo. Se verificó diabetes gestacional en 18 madres (5,6 por ciento), ninguna recibió tratamiento con hipoglucemiantes orales, 53 de ellas (16,2 por ciento) tuvieron hipertensión arterial durante la gestación y 17 (32,1 por ciento) hicieron uso de antihipertensivos; 215 (56,6 por ciento) recibieron suero glucosado al 5 por ciento durante el trabajo de parto y el parto en sí. Deben ser efectuados estudios correlacionales, analizando variables maternas y ocurrencia de hipoglucemia neonatal, con el objetivo de identificar los factores predictores de esta patología neonatal.

Utilização da insulina glargina em crianças menores de oito anos de idade / Use of insulin glargine in type 1 diabetes children with less than eight years old

OBJETIVOS: Avaliar prospectivamente a eficácia e a segurança da insulina glargina no controle metabólico de crianças com diabetes melito tipo 1 (DMT1) com menos de oito anos de idade. MÉTODOS: Foram avaliados 19 meninos e 11 meninas. Antes de iniciar a insulina glargina, todas as crianças foram colocadas em tratamento intensivo com insulina NPH e insulina asparte durante três meses. Posteriormente, os pacientes foram acompanhados por 12 meses para o tratamento com glargina. Todos os pacientes realizavam medidas da glicemia capilar 3-7 vezes ao dia. Desfechos principais: controle metabólico por meio da hemoglobina glicada (A1c); ocorrência de hipoglicemia leve (glicemia capilar < 60 mg/dL) e ocorrência de hipoglicemia grave (perda ou alteração na consciência, convulsão ou necessidade de intervenção médica). RESULTADOS: A1c média no início do estudo foi 8,68 por cento, semelhante ao valor obtido ao final dos 12 meses de tratamento com glargina (8,64 por cento; p = 0,82). A frequência de hipoglicemia leve às 3 horas da madrugada foi 1,43/3 meses por paciente com insulina NPH e de 0,28/3 meses por paciente com insulina glargina (p < 0,007). Em relação à hipoglicemia severa, houve uma diferença favorável à glargina: 0,008 versus 0,56 eventos/3 meses por paciente (p < 0,002). CONCLUSÕES: O uso da insulina glargina no tratamento de crianças com DMT1 foi considerado tão eficaz quanto o uso da NPH, apresentando, no entanto, melhor perfil de segurança caracterizado pelo menor risco de hipoglicemia noturna e severa.

OBJECTIVES: To evaluate prospectively the efficacy and safety of insulin glargine use for the metabolic control of type 1 diabetes mellitus (T1DM) children younger than eight years old. METHODS: Nineteen boys and 11 girls with T1DM were included. Before initiating insulin glargine, all children received intensive NPH and aspart insulins for three months. Afterwards, they were assisted for 12 more months for glargine treatment. All patients performed self blood glucose monitoring before and two hours after meals and in early morning (3:00 AM). Primary endpoints: metabolic control using A1C levels; frequency of mild hypoglycemia (capillary glycemia < 60 mg/dL); and frequency of severe hypoglycemia (loss or alteration of consciousness, seizures or need for medical intervention). RESULTS: Mean A1C at the study entry was 8.68 percent and after 12 months of glargine, was 8.64 percent (p = 0.82). Frequency of mild hypoglycemia at 3.00 AM was 1.43/3 months during the NPH period and 0.28/3 months during the glargine period (p < 0.007). Frequency of severe hypoglycemia was 0.56/3 months during the NPH period and 0.008/3 months during the glargine period (p < 0.002). CONCLUSIONS: The treatment of T1DM children with insulin glargine was considered as efficacious as with NPH. However, a better safety profile, disclosed by the lower incidence of nocturnal and severe hypoglycemia episodes, was observed for insulin glargine.

Efficacy, safety and acceptability of biphasic insulin aspart 30 in Indian patients with type 2 diabetes: results from the PRESENT study.

AIM: The Physicians' Routine Evaluation of Safety and Efficacy of NovoMix 30 Therapy (PRESENT) study was done to assess the safety and effectiveness of biphasic insulin aspart 30 (BIAsp 30) in patients with type 2 diabetes mellitus in routine clinical practice. MATERIALS AND METHODS: This was a prospective, multicentric, multinational, observational study in type 2 diabetes patients. The patients were transferred to BIAsp 30 with or without oral antidiabetic drugs (OADs). We present the results of 6 months of treatment in the Indian cohort (n = 3559) with type 2 diabetes mellitus who were inadequately controlled on current treatment. RESULTS: At three and six months, significant reductions from baseline were observed in the mean glycated haemoglobin (HbA1c) (-1.32% and -1.94%), fasting plasma glucose (-56.16 mg/dl and -75.24 mg/dl) and post-prandial plasma glucose (-88.74 mg/dl and -119.16 mg/dl) (p < 0.001). A significantly greater proportion of patients achieved target HbAlc of less than 7% at six months (31.1%), compared with baseline (3.1%), of which 70.4% did not report hypoglycaemia. The rate of total hypoglycaemia was reduced from 3.1 events per patient-year at baseline to 1.5 events per patient-year at end of the study. Episodes were mostly minor and diurnal. Except for two serious adverse drug reactions (ADRs) reported by one patient at 3 months, there were no reports of ADRs during the treatment period. More than 95% of patients and doctors were "very satisfied" or "satisfied" with BIAsp 30 treatment, compared to previous treatment. CONCLUSIONS: The use of BIAsp 30 monotherapy or in combination with OADs in clinical practice was effective and safe in poorly controlled Indian type 2 diabetes patients. Both patients and doctors showed a high degree of treatment satisfaction.