The efficacy and safety of saxagliptin when added to metformin therapy in patients with inadequately controlled type 2 diabetes with metformin alone.

OBJECTIVE: This 24-week trial assessed the efficacy and safety of saxagliptin as add-on therapy in patients with type 2 diabetes with inadequate glycemic control with metformin alone. RESEARCH DESIGN AND METHODS: This was a randomized, double-blind, placebo-controlled study of saxagliptin (2.5, 5, or 10 mg once daily) or placebo plus a stable dose of metformin (1,500-2,500 mg) in 743 patients (A1C > or =7.0 and < or =10.0%). Efficacy analyses were performed using an ANCOVA model using last observation carried forward methodology on primary (A1C) and secondary (fasting plasma glucose [FPG] and postprandial glucose [PPG] area under the curve [AUC]) end points. RESULTS: Saxagliptin (2.5, 5, and 10 mg) plus metformin demonstrated statistically significant adjusted mean decreases from baseline to week 24 versus placebo in A1C (-0.59, -0.69, and -0.58 vs. +0.13%; all P < 0.0001), FPG (-14.31, -22.03, and -20.50 vs. +1.24 mg/dl; all P < 0.0001), and PPG AUC (-8,891, -9,586, and -8,137 vs. -3,291 mg . min/dl; all P < 0.0001). More than twice as many patients achieved A1C <7.0% with 2.5, 5, and 10 mg saxagliptin versus placebo (37, 44, and 44 vs. 17%; all P < 0.0001). beta-Cell function and postprandial C-peptide, insulin, and glucagon AUCs improved in all saxagliptin treatment groups at week 24. Incidence of hypoglycemic adverse events and weight reductions were similar to those with placebo. CONCLUSIONS: Saxagliptin once daily added to metformin therapy was generally well tolerated and led to statistically significant improvements in glycemic indexes versus placebo added to metformin in patients with type 2 diabetes inadequately controlled with metformin alone.

Orbital metastasis as primary clinical manifestation of thyroid carcinoma: case report and literature review / Metástase orbital como manifestação clínica primária de carcinoma de tireóide: relato de caso e revisão de literatura

Capillary thyroid carcinoma (PTC) is the most common neoplasm of thyroid. It usually grows slowly and is clinically indolent, although rare, its aggressive forms with local invasion or distant metastases can occur. Metastatic thyroid carcinoma rarely involves the orbit. We reported an uncommon case of orbital metastasis of PTC. A 66-years-old woman presented proptosis of the right eye. The biopsy of the tumor in orbit revealed metastatic thyroid carcinoma. The ultrasensitive TSH level was 1,34 mUI/L and free T4 level was 1,65 ng/dL. A total thyroidectomy was performed and histopathological analysis of the nodule revealed follicular variant of papillary thyroid carcinoma. Currently, the patient has been receiving palliative chemotherapy with Clodronate Disodium. The importance of the case is due to its unusual presentation, which emerged as a primary clinical manifestation. Although rare, thyroid carcinoma should be suspected in orbit metastasis.

Carcinoma papilífero da tiróide (PTC) é a neoplasia mais comum da tiróide. Geralmente cresce lentamente e é clinicamente indolente, embora raras, as formas agressivas com invasão local ou metástases distantes podem ocorrer. Carcinoma metastático da tiróide raramente envolve a órbita. Relatamos um caso raro de metástase orbital de PTC. Uma mulher de 66 anos apresentou proptose no olho direito. A biópsia do tumor em órbita revelou carcinoma metastático da tiróide. O nível ultra-sensível do TSH foi de 1,34 mUI/L e T4 livre foi de 1,65 ng/dL. A tireoidectomia total foi realizada e a análise histopatológica do nódulo revelou carcinoma papilífero variante folicular da tiróide. Atualmente, a paciente recebe quimioterapia paliativa com clodronato dissódico. A importância do caso é devido à sua apresentação incomum que surgiu como principal manifestação clínica. Embora raro, o carcinoma da tiróide deve ser pensado em metástase orbitária.

Orbital metastasis as primary clinical manifestation of thyroid carcinoma--case report and literature review.

Capillary thyroid carcinoma (PTC) is the most common neoplasm of thyroid. It usually grows slowly and is clinically indolent; although rare, its aggressive forms with local invasion or distant metastases can occur. Metastatic thyroid carcinoma rarely involves the orbit. We reported an uncommon case of orbital metastasis of PTC. A 66-years-old woman presented proptosis of the right eye. The biopsy of the tumor in orbit revealed metastatic thyroid carcinoma. The ultrasensitive TSH level was 1,34 mUI/L and free T4 level was 1,65 ng/dL. A total thyroidectomy was performed and histopathological analysis of the nodule revealed follicular variant of papillary thyroid carcinoma. Currently, the patient has been receiving palliative chemotherapy with Clodronate Disodium. The importance of the case is due to its unusual presentation, which emerged as a primary clinical manifestation. Although rare, thyroid carcinoma should be suspected in orbit metastasis.

Event related P300 potential in NIDDM patients without cognitive impairment and its relationship with previous hypoglycemic episodes.

OBJECTIVES: The purpose of this study was to evaluate the ERP P300 in non insulin dependent diabetes mellitus (NIDDM) patients without cognitive impairment and the relationship with clinical variables, the presence of retinopathy and previous hypoglycemic episodes. METHODS: NIDDM patients (N=44) without evidence of cognitive impairment and controls (N=17) were studied clinically and with ancillary exams and the ERPs P300 were recorded. Patients were examined clinically and with the Folstein Mini-Mental Examination (MMSE) for cognitive function and all patients showed a score higher than 26 (maximal value=30). Previous hypoglycemia was evaluated through a questionnaire establishing the number of episodes and the symptoms of hypoglycemia in a scale scoring from zero to 15. RESULTS: ERP P300 latencies were significantly higher in NIDDM patients than in controls (p<0.03). ERP P300 measures were significantly related to age (Pearson, p<0.01) and not to metabolic variables, disease duration or the presence of retinopathy. Severity of hypoglycemia was not associated to ERP P300 latency. CONCLUSIONS: Our study supports the evidence that NIDDM patients, without signs of nervous system involvement, have ERP P300 alterations and this is not related to retinopathy, metabolic variables or previous hypoglycemic episodes. Chronic hyperglycemia may alter brain glucose transport and increase tolerance to hypoglycemia effects in the nervous system.

Comparison between continuous subcutaneous insulin infusion and multiple insulin injection therapy in type 1 diabetes mellitus: 18-month follow-up.

OBJECTIVE: To compare the results with continuous subcutaneous insulin infusion (CSII) versus multiple daily injections (MDI) of insulin in the treatment of type 1 diabetes during 18 months of follow-up. METHODS: We prospectively studied 29 patients with type 1 diabetes in Brazil; 17 patients elected to change from conventional insulin therapy (2 injections daily) (N = 3) or MDI (N = 14) to CSII therapy, and the other 12 continued to receive MDI therapy. All patients were treated with insulin lispro; patients in the MDI treatment group also received NPH insulin. We compared hemoglobin A1c (HbA1c) values, determined at baseline and every 3 months, between the two treatment groups. Other variables analyzed included weight, body mass index, total daily dose of insulin, and incidence of severe hypoglycemia. RESULTS: Patients in the CSII group had a significant decrease (P<0.001) in mean HbA1c at 18 months in comparison with baseline (8.3% versus 6.5%). In the MDI group, no significant changes were found in mean HbA1c. After 3 months of treatment, patients in the CSII group had a significantly lower mean HbA1c level than did patients receiving MDI (P<0.05). Of the 17 patients treated with CSII, all had HbA1c values less than 7.5% at 18 months, and 13 (76%) had HbA1c levels less than 7%. Although no significant variations in weight were observed in either group, the insulin/weight ratio decreased in the CSII group from baseline to 18 months (0.8 U/kg to 0.6 U/kg; P = 0.02). No episodes of severe hypoglycemia were noted in either group. CONCLUSION: Patients with diabetes treated with insulin lispro have better glycemic control with CSII than with MDI. Most of our patients in the CSII group were able to achieve target HbA1c levels less than 7% at 18 months without an increase in hypoglycemic episodes.

Tratamento do diabetes mellitus tipo 1 com bomba de infusäo subcutânea contínua de insulina e insulina lispro / Type 1 diabetes mellitus treatment with a continuous subcutaneous insulin infusion pump and insulin lispro

Objetivo: Avaliar a eficácia do tratamento do diabetes mellitus tipo 1 por um período de 18 meses, em 17 pacientes, utilizando-se um processo de infusäo subcutânea contínua de insulina (ISCI) e de um análogo da insulina (insulina lispro) através de uma bomba infusora. Estudamos os seguintes parâmetros: hemoglobina glicosilada, peso, índice de massa corpórea, relaçäo insulina/peso, quantidade de insulina/dia administrada, relaçäo da insulina administrada na forma de .bolus (antes das refeiçöes) com a insulina basal e efeitos adversos desta terapia. Após esse período observamos que os pacientes estavam melhor controlados com níveis de HbAI c significativamente reduzidos (p< 0,05). Apresentavam uma reduçäo significativa da relaçäo insulina/peso (p< 0,05) e melhor aproveitamento da insulina relacionado a alimentaçäo dado pelo aumento significativo da relaçäo bolus/basal quando comparado com a relaçäo de insulina regular/NPH antes do tratamento (p< 0,05).