Effect of TCF7L2 polymorphism on pancreatic hormones after exenatide in type 2 diabetes.

BACKGROUND: Glucagon-like peptide 1 (GLP-1) stimulates insulin secretion and reduces blood glucose in type 2 diabetes mellitus (T2DM). TCF7L2 rs7903146 polymorphism has been associated with decreased insulin secretion, reduced GLP-1 action, and possible impaired peripheral insulin sensitivity. OBJECTIVES: To evaluate the postprandial pancreatic hormone response in patients with T2DM carriers of the TCF7L2 variant rs7903146 (CT/TT) compared with noncarriers of this variant (CC) after treatment with the GLP-1 agonist exenatide. METHODS: Intervention study. Patients with T2DM (n = 162) were genotyped for the TCF7L2 rs7903146 single nucleotide polymorphism (SNP). Individuals with CT/TT and CC genotypes were compared regarding basal serum levels of glucose, glycosylated hemoglobin A1C (HbA1c), HDL, uric acid, insulin, and C-peptide. A subset of 56 individuals was evaluated during a 500-calorie mixed-meal test with measurements of glucose, insulin, proinsulin, C-peptide and glucagon before and after treatment with exenatide for 8 weeks. RESULTS: Patients with genotypes CC and CT/TT presented similar glucose area under the curve (AUC) 0-180 min before treatment and a similar decrease after treatment (p < 0.001). Before exenatide, insulin levels at 30-120 min were higher in CT/TT versus CC subjects (p < 0.05). After treatment with exenatide, only CT/TT individuals demonstrated insulin reduction at 30-180 min during the meal test (p < 0.05). Patients with the CC genotype presented no differences in insulin concentrations before and after treatment. The areas under the glucagon curve between 0 and 180 min were similar before treatment and reduced after treatment in both groups (p < 0.001). CONCLUSIONS: The presence of the TCF7L2 rs7903146 T allele in patients with T2DM was associated with increased secretion of insulin response to a mixed-meal test. Furthermore, after treatment with exenatide, only the carriers of the T allele showed significantly decreased postprandial plasma insulin peak levels comparing with non carriers.

TCF7L2 correlation in both insulin secretion and postprandial insulin sensitivity.

BACKGROUND: The TCF7L2 rs7903146 variant is strongly associated with type 2 diabetes mellitus (T2DM). However, the mechanisms involved in this association remain unknown and may include extrapancreatic effects. The aim of this study was to perform a metabolic characterization of T2DM patients with and without the TCF7L2 rs7903146 risk T allele and analyze some influences of the TCF7L2 genotype on glucose metabolism. METHODS: Patients with T2DM (n = 162) were genotyped for the TCF7L2 rs7903146 single nucleotide polymorphism. Individuals with CT/TT and CC genotypes were compared regarding basal serum levels of glucose, glycosylated hemoglobin A1C, HDL, uric acid, insulin, and C-peptide. A subset of 56 individuals was evaluated during a 500-calorie mixed-meal test with measurements of glucose, insulin, proinsulin, C-peptide and glucagon. Additional secondary assessments included determination of insulinogenic index (IGI30), and insulin sensitivity (%S) and resistance (IR) by Homeostatic model assessment (HOMA). RESULTS: Patients with the CT/TT genotype showed lower baseline plasma concentrations of C-peptide when compared with those with the CC genotype. Of the 56 individuals who participated in the mixed-meal test, 26 and 30 had the CC and CT/TT genotypes, respectively. CT/TT subjects, compared with CC individuals, had higher post prandial plasma levels of insulin and C-peptide at 30-120 min (p < 0.05) and proinsulin at 45-240 min (p < 0.05). Interestingly CT/TT individuals presented at baseline higher %S (p = 0.021), and lower IR (p = 0.020) than CC individuals. No significant differences in IGI30 values were observed between groups. CONCLUSIONS: The T2DM individuals carrying the rs7903146 T allele of the TCF7L2 gene presented higher IR pattern in response to a mix-meal test, different of beta cell function at baseline assessed by C-peptide levels which was lower, and Homa-IR was lower when comparing with non-carriers.

Percutaneous ethanol injection versus conservative treatment for benign cystic and mixed thyroid nodules

ABSTRACT Objective To evaluate the efficacy and safety of percutaneous ethanol injection (PEI) in reducing the volume of cystic and mixed thyroid nodules. Materials and methods A total of 36 patients with nodules treated with PEI and 13 individuals who declined PEI and were followed clinically or received other non surgical treatment (control group). Assessments were performed at baseline (immediately before treatment in the PEI group or evaluation of the nodule on ultrasonography in the control group) at short-term (on average 30 days after the last injection in the PEI group), and long-term (on average 14 months after baseline in the PEI group or 26 months after baseline in the control group). Results In the PEI group, the mean baseline volume of 10.4 ± 9.8 cm3 reduced at short-term follow-up to 2.9 ± 3.1 cm3 (67.7 ± 19.9%, p < 0.001) and at long-term follow-up to 2.0 ± 2.5 cm3 (78.2 ± 19.5%, p < 0.01 versus baseline and p = 0.009 versus short-term follow-up). Both types of nodules showed similar degrees of reduction. In the control group, mean volume was 5.8 ± 3.4 cm3 at baseline and 6.2 ± 3.0 cm3 at long-term follow-up (p = 0.507). Compared with the control group, the PEI group showed larger reduction (p < 0.001). Conclusions PEI is effective in reducing the volume of cystic and mixed benign thyroid nodules, with sustained long-term efficacy and better outcome when compared with conservative therapies. Treatment with PEI is a safe alternative, with minimal, transient and self-limited adverse events.

Percutaneous ethanol injection versus conservative treatment for benign cystic and mixed thyroid nodules.

OBJECTIVE: To evaluate the efficacy and safety of percutaneous ethanol injection (PEI) in reducing the volume of cystic and mixed thyroid nodules. MATERIALS AND METHODS: A total of 36 patients with nodules treated with PEI and 13 individuals who declined PEI and were followed clinically or received other non surgical treatment (control group). Assessments were performed at baseline (immediately before treatment in the PEI group or evaluation of the nodule on ultrasonography in the control group) at short-term (on average 30 days after the last injection in the PEI group), and long-term (on average 14 months after baseline in the PEI group or 26 months after baseline in the control group). RESULTS: In the PEI group, the mean baseline volume of 10.4 ± 9.8 cm3 reduced at short-term follow-up to 2.9 ± 3.1 cm3 (67.7 ± 19.9%, p < 0.001) and at long-term follow-up to 2.0 ± 2.5 cm3 (78.2 ± 19.5%, p < 0.01 versus baseline and p = 0.009 versus short-term follow-up). Both types of nodules showed similar degrees of reduction. In the control group, mean volume was 5.8 ± 3.4 cm3 at baseline and 6.2 ± 3.0 cm3 at long-term follow-up (p = 0.507). Compared with the control group, the PEI group showed larger reduction (p < 0.001). CONCLUSIONS: PEI is effective in reducing the volume of cystic and mixed benign thyroid nodules, with sustained long-term efficacy and better outcome when compared with conservative therapies. Treatment with PEI is a safe alternative, with minimal, transient and self-limited adverse events.

Clinical variables associated with depression in patients with type 2 diabetes.

BACKGROUND: the aim of the study was to evaluate the relationship between type 2 diabetes (T2DM), depression and depressive symptoms and their clinical impact on T2DM. METHODS: the authors evaluated 214 outpatients, 105 with diabetes (T2DM group) and 109 non-diabetics (control group), with ages ranging between 50 and 75 years (T2DM group 65.1 ± 5.6 years, control group 63.4 ± 5.8 years). Use of antidepressant treatment or score ≥ 16 on the Beck depression inventory (BDI) was considered depression. Complications of diabetes and total symptom score (TSS) for peripheral neuropathy were reported by patients. RESULTS: diabetes group had a higher frequency of depression (35.2%) compared to controls (21.1%) (p=0,021), with 2.4 times increased risk of depression. The presence of depressive symptoms was also higher in T2DM group (mean BDI 9.5 ± 8.8 versus 6.9 ± 6.2; p=0.039). Symptoms of diabetic neuropathy were higher in depressed subjects. The metabolic control and presence of complications in T2DM group were not associated with depression. CONCLUSION: T2DM led to an increased risk of depression, but this did not influence the metabolic control or the presence of other complications.

Clinical variables associated with depression in patients with type 2 diabetes / Características clínicas associadas à depressão em pacientes com diabetes tipo 2

SummaryBackground:the aim of the study was to evaluate the relationship between type 2 diabetes (T2DM), depression and depressive symptoms and their clinical impact on T2DM.Methods:the authors evaluated 214 outpatients, 105 with diabetes (T2DM group) and 109 non-diabetics (control group), with ages ranging between 50 and 75 years (T2DM group 65.1 ± 5.6 years, control group 63.4 ± 5.8 years). Use of antidepressant treatment or score ≥ 16 on the Beck depression inventory (BDI) was considered depression. Complications of diabetes and total symptom score (TSS) for peripheral neuropathy were reported by patients.Results:diabetes group had a higher frequency of depression (35.2%) compared to controls (21.1%) (p=0,021), with 2.4 times increased risk of depression. The presence of depressive symptoms was also higher in T2DM group (mean BDI 9.5 ± 8.8 versus 6.9 ± 6.2; p=0.039). Symptoms of diabetic neuropathy were higher in depressed subjects. The metabolic control and presence of complications in T2DM group were not associated with depression.Conclusion:T2DM led to an increased risk of depression, but this did not influence the metabolic control or the presence of other complications.

ResumoObjetivo:avaliar a relação entre diabetes mellitus tipo 2 (DM2), depressão e sintomas depressivos e seu impacto no controle clínico do DM2.Métodos:foram avaliados 214 pacientes ambulatoriais, 105 com DM2 e 109 não diabéticos, com idade entre 55 e 75 anos (grupo DM2 65,1±5,6 anos e grupo controle 63,4±5,8 anos). Considerou-se depressão o uso de tratamento antidepressivo ou escore ≥16 no inventário de Beck (BDI). Complicações do DM2 e escore total de sintomas (TSS) para neuropatia periférica foram questionados aos pacientes.Resultados:o grupo DM2 apresentou maior frequência de depressão (35,2%) em relação aos controles (21,1%) (p=0,021), com um risco 2,4 vezes maior de apresentar depressão. A presença de sintomas depressivos também foi superior no grupo DM2 (média BDI 9,5±8,8 versus 6,9±6,2; p=0,039). Os sintomas de neuropatia diabética foram superiores nos depressivos. O controle metabólico e a presença de complicações no grupo DM2 não foram associados à depressão.Conclusão:o DM2 determinou um maior risco de depressão; porém, essa associação não influenciou o controle metabólico e a presença de outras complicações da doença.

Redução da mobilidade funcional e da capacidade cognitiva no diabetes melito tipo 2 / Reduction of functional mobility and cognitive capacity in type 2 diabetes mellitus

Objetivos Avaliar a mobilidade funcional e sua relação com a capacidade cognitiva em pacientes com diabetes tipo 2 (DM2) entre 50 e 65 anos de idade, e com menos de 10 anos de diagnóstico. Materiais e métodos Estudo observacional, analítico e transversal envolvendo indivíduos não diabéticos e pacientes com DM2 com controle glicêmico inadequado, selecionados por amostra de conveniência. Em ambos os grupos, foram aplicados questionário estruturado, avaliação cognitiva com Miniexame do Estado Mental (MEEM) e teste do relógio (TDR), além da avaliação de mobilidade funcional pelo teste Timed Up & GO (TUG). Resultados No TUG os pacientes com DM2 apresentaram tempo médio de 11,27 segundos versus 9,52 segundos nos controles (p = 0,013). A associação entre declínio cognitivo e dismobilidade foi positiva nos indivíduos com DM2 (p = 0,037). No subgrupo que apresentou dismobilidade e declínio cognitivo associados, 18% eram portadores de DM2 e 1,6% era do grupo sem DM2 (p < 0,01). Conclusões Pacientes com DM2 apresentaram pior mobilidade funcional e desempenho cognitivo, favorecendo a hipótese de que o DM2 influencia a mobilidade funcional e capacidade cognitiva antes do aparecimento de complicações vasculares ou neuropáticas. Esses dados sugerem que a hiperglicemia é um fator agravante no desempenho de atividades que exijam funções mentais como atenção, orientação e memória de trabalho. Arq Bras Endocrinol Metab. 2014;58(9):946-52 .

Objectives The aim of the present study was to evaluate the functional mobility and its relationship to cognitive ability in patients with type 2 diabetes (T2DM), age between 50 and 65 years and under 10 years of diagnosis. Materials and methods An observational, analytical and cross-sectional study, involving no diabetic and type 2 diabetic individuals with inadequate glycemic control, selected by convenience sampling. In both groups, were administered structured questionnaire and cognitive assessment with Mini-Mental State Examination (MMSE) and the clock drawing test (CDT), besides assessment of functional mobility by the Timed Up & Go (TUG). Results In TUG, DM2 patients presented a mean time of 11.27 seconds versus 9.52 seconds (p = 0.013). The association between cognitive decline and decrease of mobility was positive in individuals with T2DM (p = 0.037). In the subgroup that showed decrease of mobility and associated cognitive decline, 18% were patients with DM2 and 1.6% were individuals without T2DM (p < 0.01). Conclusions Patients with T2DM presented worse functional mobility and cognitive performance, supporting the hypothesis that DM2 influence functional mobility and cognitive ability, regardless of neuropathic or vascular complications. These data suggest that hyperglycemia is an aggravating factor in the performance of activities requiring mental functions such as attention, working memory and orientation. Arq Bras Endocrinol Metab. 2014;58(9):946-52 .

[Reduction of functional mobility and cognitive capacity in type 2 diabetes mellitus]. / Redução da mobilidade funcional e da capacidade cognitiva no diabetes melito tipo 2.

OBJECTIVES: The aim of the present study was to evaluate the functional mobility and its relationship to cognitive ability in patients with type 2 diabetes (T2DM), age between 50 and 65 years and under 10 years of diagnosis. MATERIALS AND METHODS: An observational, analytical and cross-sectional study, involving no diabetic and type 2 diabetic individuals with inadequate glycemic control, selected by convenience sampling. In both groups, were administered structured questionnaire and cognitive assessment with Mini-Mental State Examination (MMSE) and the clock drawing test (CDT), besides assessment of functional mobility by the Timed Up & Go (TUG). RESULTS: In TUG, DM2 patients presented a mean time of 11.27 seconds versus 9.52 seconds (p = 0.013). The association between cognitive decline and decrease of mobility was positive in individuals with T2DM (p = 0.037). In the subgroup that showed decrease of mobility and associated cognitive decline, 18% were patients with DM2 and 1.6% were individuals without T2DM (p < 0.01). CONCLUSIONS: Patients with T2DM presented worse functional mobility and cognitive performance, supporting the hypothesis that DM2 influence functional mobility and cognitive ability, regardless of neuropathic or vascular complications. These data suggest that hyperglycemia is an aggravating factor in the performance of activities requiring mental functions such as attention, working memory and orientation.

Comparative analysis of risk for falls in patients with and without type 2 diabetes mellitus.

OBJECTIVE: To compare frequency and risk of falls based on a functional mobility test in diabetic and non-diabetic individuals. METHODS: Cross-sectional study involving patients with and without type 2 diabetes mellitus (DM2) selected by convenience sampling. Men and women between the ages of 50 and 65 were included and divided as group 1 (G1) - with DM2 diagnosis for < 10 years fasting blood glucose at interview/test time, as well as prior > 200 mg/dL; and group 2 (G2) - no diabetes, same age group, and fasting blood glucose < 100 mg/dL. Both groups responded to a structured questionnaire about their health, fall risk, and underwent a physical exam and a mobility assessment test (Timed Up and Go - TUG). The results were analyzed by the software SPSS, with TUG being categorized in ranges of risk for fall. We considered that the risk was positive for all those who fit into medium- and high-risk range. RESULTS: Fifty patients with DM2 and 68 patients without DM2 were assessed. There were no statistical differences in the number of falls between the groups, however non-diabetic subjects obtained a higher performance in TUG test (p = 0.003) as the risk categories were observed. Reduced visual acuity and difficulty in getting up were more frequently reported in G1 (p < 0.05). CONCLUSION: There appears to be an association between hyperglycemic status and poorer mobility, with an increased fall risk even in younger patients and in those with shorter disease duration.

Análise comparativa do risco de quedas entre pacientes com e sem diabetes mellitus tipo 2 / Comparative analysis of risk for falls in patients with and without type 2 diabetes mellitus

OBJETIVO: Comparar a frequência e o risco de quedas baseado em teste de mobilidade funcional entre diabéticos e não diabéticos. MÉTODOS: Estudo transversal envolvendo pacientes com e sem diabetes mellitus tipo 2 (DM2) selecionados por amostra de conveniência. Foram incluídos homens e mulheres entre 50 e 65 anos, sendo divididos em: grupo 1 (G1) - com diagnóstico de DM2 < 10 anos, glicemia de jejum > 200 mg/dL no momento da inclusão e prévia; e grupo 2 (G2) - sem diabetes, de mesma faixa etária, e glicemia de jejum < 100 mg/dL. Ambos responderam a questionário estruturado sobre sua saúde, risco de quedas e se submeteram a exame físico e ao Timed Up & Go (TUG), teste de avaliação de mobilidade. Os resultados foram analisados pelo programa Statistical Package for the Social Sciences (SPSS), sendo que o TUG foi categorizado em faixas de risco para quedas. Consideramos risco positivo para todos os que se enquadraram em médio e alto risco. RESULTADOS: Foram avaliados 50 pacientes com DM2 e 68 sem a doença. Não houve diferença estatística entre o número de quedas para os grupos, entretanto os não diabéticos obtiveram melhor desempenho no teste TUG (p = 0,003) quando observadas as categorias de risco descritas. A redução da acuidade visual e a dificuldade para levantar foram mais referidas no G1 (p < 0,05). CONCLUSÃO: Parece haver uma associação entre estado hiperglicêmico e piora da mobilidade, com risco aumentado de quedas, mesmo em pacientes mais jovens e com menor tempo de doença.

OBJECTIVE: To compare frequency and risk of falls based on a functional mobility test in diabetic and non-diabetic individuals. METHODS: Cross-sectional study involving patients with and without type 2 diabetes mellitus (DM2) selected by convenience sampling. Men and women between the ages of 50 and 65 were included and divided as group 1 (G1) - with DM2 diagnosis for < 10 years fasting blood glucose at interview/test time, as well as prior > 200 mg/dL; and group 2 (G2) - no diabetes, same age group, and fasting blood glucose < 100 mg/dL. Both groups responded to a structured questionnaire about their health, fall risk, and underwent a physical exam and a mobility assessment test (Timed Up and Go - TUG). The results were analyzed by the software SPSS, with TUG being categorized in ranges of risk for fall. We considered that the risk was positive for all those who fit into medium- and high-risk range. RESULTS: Fifty patients with DM2 and 68 patients without DM2 were assessed. There were no statistical differences in the number of falls between the groups, however non-diabetic subjects obtained a higher performance in TUG test (p = 0.003) as the risk categories were observed. Reduced visual acuity and difficulty in getting up were more frequently reported in G1 (p < 0.05). CONCLUSION: There appears to be an association between hyperglycemic status and poorer mobility, with an increased fall risk even in younger patients and in those with shorter disease duration.