CD226 rs763361 is associated with the susceptibility to type 1 diabetes and greater frequency of GAD65 autoantibody in a Brazilian cohort.

CD226 rs763361 variant increases susceptibility to type 1 diabetes (T1D) in Caucasians. There is no data about CD226 variants in the very heterogeneous Brazilian population bearing a wide degree of admixture. We investigated its association with T1D susceptibility, clinical phenotypes, and autoimmune manifestations (islet and extrapancreatic autoantibodies). Casuistry. 532 T1D patients and 594 controls in a case-control study. Initially, CD226 coding regions and boundaries were sequenced in a subset of 106 T1D patients and 102 controls. In a second step, two CD226 variants, rs763361 (exon 7) and rs727088 (3' UTR region), involved with CD226 regulation, were genotyped in the entire cohort. C-peptide and autoantibody levels were determined. No new polymorphic variant was found. The variants rs763361 and rs727088 were in strong linkage disequilibrium. The TT genotype of rs763361 was associated with TID risk (OR = 1.503; 95% CI = 1.135-1.991; P = 0.0044), mainly in females (P = 0.0012), greater frequency of anti-GAD autoantibody (31.9% × 24.5%; OR = 1.57; CI = 1.136-2.194; P = 0.0081), and lower C-peptide levels when compared to those with TC + CC genotypes (0.41 ± 0.30 ng/dL versus 0.70 ± 0.53 ng/dL P = 0.0218). Conclusions. The rs763361 variant of CD226 gene (TT genotype) was associated with susceptibility to T1D and with the degree of aggressiveness of the disease in T1D patients from Brazil. Ancestry had no effect.

Postprandial glucose-lowering effect of cagaita (Eugenia dysenterica DC) fruit juice in dysglycemic subjects with metabolic syndrome: An exploratory study.

Cagaita (Eugenia dysenterica DC) is an ellagitannin-containing Myrtaceae fruit from Cerrado biome. This fruit seems to be a promising candidate for an adjuvant in glucose regulation in healthy subjects. However, it is not known whether cagaita juice would have the same effect on dysglycemic subjects with metabolic syndrome (MetS). Therefore, the present work aimed to evaluate the effect of cagaita fruit juice on postprandial glycemia in dysglycemic subjects with MetS, and whether cagaita ellagitannins could be metabolized to urolithins. To evaluate glycemic effects, two different meals were consumed by volunteers (n = 12) with a 1-week interval among them. The first one consisted of white bread (50 g) plus water (300 mL) as a control; the second one, white bread (50 g) plus clarified cagaita juice (300 mL). Bioavailability was assessed in 24 h urine, after the consumption of a single amount of 300 mL of cagaita juice by healthy (n = 16) and MetS subjects (n = 7). The results showed that dysglycemic subjects with MetS presented a 53% reduction of incremental area under the curve (iAUC) of glucose, 38% reduction of insulin, 78% reduction of GIP (glucose-dependent insulinotropic polypeptide), and 58% reduction of C-peptide (p < 0.05), after the consumption of cagaita juice along with bread, in comparison to control water. However, both GLP-1 (glucagon-like peptide-1) and glucagon were not affected by cagaita juice ingestion. Concerning bioavailability, it was observed, for the first time, the metabolization of cagaita ellagitannins to urolithins by healthy and dysglycemic individuals with MetS, with a prevalence of metabotype B in both groups (44% and 42%, respectively), followed by metabotype A (37% and 29%, respectively), and metabotype 0 (19% and 29%, respectively).

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.

Improvement of Body Composition and Quality of Life Following Intragastric Balloon.

BACKGROUND: The aim is to evaluate the effects of IGB in overweight or class I obese patients, by analyzing body composition and quality of life (QOL). METHODS: Prospective study including patients with BMI 27-34.9 kg/m2.body composition analysis (BCA) was performed before IGB implantation and its removal, after 6 months of treatment. QOL was assessed by the Short Form 36 (SF-36) Health Survey at baseline and after treatment. RESULTS: Forty patients were included in this study, but four were excluded. The total weight decreased by 12.29 kg after 6 months of use of IGB, which corresponds to loss of 13.69% of the total weight. There was a significant reduction in body fat mass and fat area. QOL improved in all eight sections analyzed (p < 0.001 to 0.041): functional capacity, physical aspects, pain, general health status, vitality, social aspects, emotional aspects, and mental health. CONCLUSIONS: IGB induces not only weight loss but changes in body composition through the reduction of body fat mass and fat area. Furthermore, it improves QOL.

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.

Estrogen treatment improves arterial distensibility, fibrinolysis, and metabolic profile in postmenopausal women with type 2 diabetes mellitus.

The effects of isolated estrogen therapy on the hemostatic system and arterial distensibility were determined in postmenopausal females with type 2 diabetes mellitus. This was a prospective nonrandomized study of 19 subjects (age, 56.2 +/- 4.7 years; body mass index, 27.8 +/- 2.4 kg/m(2) [mean +/- SD]). Inclusion was done after 2 months of glycemic and blood pressure control. The study consisted of 4 months of placebo treatment immediately followed by an equal period of oral conjugated equine estrogens (CEE) 0.625 mg/d. Measures included anthropometrics, a metabolic profile (oral glucose tolerance test and fasting glycated hemoglobin, total cholesterol and fractions, and triglyceride levels), and coagulation and fibrinolytic factors at the end of the placebo period and after 4 months of oral CEE. Conjugated equine estrogen therapy decreased plasminogen activator inhibitor 1 (placebo x CEE: 16.33 +/- 9.11 x 13.08 +/- 8.87 UI/mL, P < .03) and increased factor VIII activity (134.11% +/- 46.18% x 145.33% +/- 42.04%, P < .04). An increase in high-density lipoprotein cholesterol levels (placebo x CEE: 42.47 +/- 6.80 x 53.32 +/- 11.89 mg/dL, P < .01), and a decrease in glycated hemoglobin (8.45% +/- 1.30% vs 7.58% +/- 1.06%, P < .02) and in fasting glucose levels (121.51 +/- 21.05 x 111.21 +/- 20.74 mg/dL, P = .02) followed CEE therapy. Pulse wave velocity and augmentation index were performed by applanation tonometry and were obtained at the end of the placebo period (placebo), again after an intravenous load of 1.25 mg of CEE (short-term), and after 4 months of oral CEE (long-term). A significant decrease in central (carotid-femoral) pulse wave velocity was seen both after short- and long-term CEE (placebo vs short-term vs long-term: 9.36 +/- 2.58 vs 8.26 +/- 2.20 vs 7.98 +/- 1.90 m/s, respectively [analysis of variance, P < .03]; placebo vs short-term, P < .05; placebo vs long-term, P < .01), whereas augmentation index decreased only after long-term CEE (placebo vs short-term vs long-term: 39.14% +/- 6.94% vs 37.48% +/- 8.67% vs 34.3.3% +/- 8.11% [analysis of variance, P < .05], respectively; placebo vs long-term, P < .05). Long-term administration of CEE leads to an improvement in fibrinolysis and arterial distensibility, associated with an increase of the intrinsic coagulation pathway in postmenopausal women with type 2 diabetes mellitus.

Short and Long Term Effects of a DPP-4 Inhibitor Versus Bedtime NPH Insulin as ADD-ON Therapy in Patients with Type 2 Diabetes.

BACKGROUND: We conducted a comparison between the dipeptidyl-peptidase-4(DPP-4) inhibitor sitagliptin versus NPH insulin as an add-on therapies in patients with type 2 diabetes mellitus (T2D) failing oral medications. The objective was to ascertain the better indication in long-duration diabetes. METHODS: thirty-five T2D patients inadequately controlled with metformin plus glyburide were randomized to receive sitagliptin (n=18) or bedtime NPH insulin (n=17) for 12 months. HbA1c levels and a metabolic and hormonal profile at fasting and post-meal (every 30 minutes for 4 hours) were evaluated before and after 6 months (short-term) and 12 months (long-term) after adding sitagliptin or bedtime NPH insulin to their drug regime. RESULTS: Sitagliptin and NPH insulin decreased HbA1c levels equally after 6 months (p<0.001) with no further improvement after 12 months: sitagliptin (8.1±0.7% vs. 7.3±0.8% vs. 7.4±1.9%) and insulin (8.1±0.6% vs. 7.3±0.7% vs. 7.2±1.0%). Fasting glucose, fasting and postprandial triglyceride and C-peptide levels were also reduced by NPH insulin whereas postprandial insulin was decreased by sitagliptin. Body weight and postchallenge free fatty acid levels increased with insulin treatment. The transitory suppression (at 6 months) of postprandial proinsulin levels with both therapies, and of glucagon with sitagliptin, was followed by values similar or worse to those at pre-treatment. CONCLUSION: The use of either NPH insulin or a DPP-4 inhibitor as add-on treatments improves glucose control in patients with T2D failing on metformin plus glyburide therapy. The results were not attributed to a permanent improvement in alpha or beta cell function in patients with long-duration diabetes.

Effects of nateglinide and rosiglitazone on pancreatic alpha- and beta-cells, GLP-1 secretion and inflammatory markers in patients with type 2 diabetes: randomized crossover clinical study.

BACKGROUND: To compare the effects of nateglinide and rosiglitazone on inflammatory markers, GLP-1 levels and metabolic profile in patients with type 2 diabetes (DM2). METHODS: A prospective study was performed in 20 patients with DM2, mean age 51.82 ± 8.05 years, previously treated with dietary intervention. Participants were randomized into rosiglitazone (4-8 mg/day) or nateglinide (120 mg 3 times a day) therapy. After 4 months, the patients were crossed-over with 8 weeks washout period to the alternative treatment for an additional 4-month period on similar dosage schedule. The following variables were assessed before and after 4 months of each treatment period: (1) a test with a standardized 500 calories meal for 5 h including frequent measurements of glucose, insulin, glucagon, proinsulin, GLP-1, free fat acids (FFA), and triglycerides levels was obtained. The lipid profile and HbA1 levels were measured at fasting. (2) Haemostatic and inflammatory markers: platelet aggregation, fibrinogen, PAI-1 activity, C reactive protein (CRP), IL-6, TNF-α, leptin, sICAM and TGFß levels. RESULTS: Both therapy decreased blood glucose levels under the postprandial curve but neither affected glucagon and GLP-1 levels. Nateglinide was associated with higher insulin and pro-insulin secretion, but similar pro-insulin/insulin ratio when compared with rosiglitazone. Only rosiglitazone decreased Homa ß, PAI-1 activity, CRP, fibrinogen, TGFß, FFA and triglyceride levels. CONCLUSIONS: Nateglinide and rosiglitazone were effective in improving glucose and lipid profile and ß cell function, but rosiglitazone afforded a better anti-inflammatory effect. No drug restored alpha cell sensitivity or changed GLP-1 levels. Maintenance of haemostatic factors, inflammatory factors and glucagon levels can be related to the continuously worsening of cardiovascular function and glucose control observed in DM2.

[Diabetic retinopathy]. / Retinopatia diabética.

Diabetic retinopathy is a frequently observed complication in both type 1 and type 2 diabetes, specially in patients with long term disease and poor glicemic control. Irreversible visual loss appears at the final stages of diabetic retinopathy and it is considered one of the most tragic of diabetic complications. It is also considered an important factor of morbidity and has a high economical impact once it is the leading cause of blindness. The pathophysiology of the retinal microvascular alterations is related to the chronic hyperglycemia that leads to the following circulatory disturbances: loss of vascular tonus, increase in vascular permeability, edema and exudation, with vascular obstruction and ischemia that stimulates neovascularization, which may lead to fibrous retraction and vitreous hemorrhages with retinal detachment. Recent studies have indicated that the strict glicemic and blood pressure controls are effective in reducing or blocking the progression of retinopathy. Up to now no pharmacological agents have shown to be effective in preventing or reducing neovascularization and visual loss. Presently, the most effective available treatment for proliferative retinopathy is laser photocoagulation. Further studies are needed to obtain new products and technologies that could effectively prevent or block retinopathy progression.

Left ventricular diastolic function in patients with type 2 diabetes treated with a dipeptidyl peptidase-4 inhibitor- a pilot study.

BACKGROUND: Blood glucose control is fundamental albeit not enough to prevent diabetic macrovascular complications. Dipeptidyl peptidase-4 (DPP-4) inhibitors are effective in improving metabolic parameters in patients with type 2 diabetes mellitus (T2DM) but little is known about its cardiovascular effects. We compared the DPP-4 inhibitor sitagliptin with bedtime NPH insulin (NPH) as add-on therapy in patients with T2DM, aiming to ascertain which drug would have additional cardioprotective effects. METHODS: Thirty-five T2DM patients inadequately controlled with metformin plus glyburide were randomized to receive sitagliptin (n = 18) or NPH (n = 17) for 24 weeks. Fasting plasma glucose, HbA1c, lipid profile, C-reactive protein, active glucagon-like peptide (aGLP-1) levels, 24-hour ambulatory blood pressure measurement and comprehensive 2-dimensional echocardiogram were determined before and after treatments. RESULTS: Both sitagliptin and NPH therapies decreased HbA1c levels after 24 weeks. Fasting plasma glucose and triglyceride levels decreased in the NPH group whereas only sitagliptin increased aGLP-1 levels. Left ventricular diastolic dysfunction (LVDD) was detected in 58.6% of twenty-nine patients evaluated. Beneficial effects in LVDD were observed in 75% and 11% of patients treated with sitagliptin and NPH, respectively (p = 0.015). Neither therapy changed C-reactive protein or blood pressure. CONCLUSIONS: Sitagliptin and bedtime NPH were similarly effective on glucose control. Improvement in LVDD in T2DM patients treated with sitagliptin was suggested, probably related to the increase of aGLP-1 levels. Therefore, DPP-4 inhibitor seems to have cardioprotective effects independent of glucose control and may have a role in the prevention of diabetic cardiomyopathy.

[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.

Metformin, but not glimepiride, improves carotid artery diameter and blood flow in patients with type 2 diabetes mellitus.

OBJECTIVE: To compare the effects of glimepiride and metformin on vascular reactivity, hemostatic factors and glucose and lipid profiles in patients with type 2 diabetes. METHODS: A prospective study was performed in 16 uncontrolled patients with diabetes previously treated with dietary intervention. The participants were randomized into metformin or glimepiride therapy groups. After four months, the patients were crossed over with no washout period to the alternative treatment for an additional four-month period on similar dosage schedules. The following variables were assessed before and after four months of each treatment: 1) fasting glycemia, insulin, catecholamines, lipid profiles and HbA1 levels; 2) t-PA and PAI-1 (antigen and activity), platelet aggregation and fibrinogen and plasminogen levels; and 3) the flow indices of the carotid and brachial arteries. In addition, at the end of each period, a 12-hour metabolic profile was obtained after fasting and every 2 hours thereafter. RESULTS: Both therapies resulted in similar decreases in fasting glucose, triglyceride and norepinephrine levels, and they increased the fibrinolytic factor plasminogen but decreased t-PA activity. Metformin caused lower insulin and pro-insulin levels and higher glucagon levels and increased systolic carotid diameter and blood flow. Neither metformin nor glimepiride affected endothelial-dependent or endothelial-independent vasodilation of the brachial artery. CONCLUSIONS: Glimepiride and metformin were effective in improving glucose and lipid profiles and norepinephrine levels. Metformin afforded more protection against macrovascular diabetes complications, increased systolic carotid artery diameter and total and systolic blood flow, and decreased insulin levels. As both therapies increased plasminogen levels but reduced t-PA activity, a coagulation process was likely still ongoing.

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 .

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.

Metformin, but not glimepiride, improves carotid artery diameter and blood flow in patients with type 2 diabetes mellitus

OBJECTIVE: To compare the effects of glimepiride and metformin on vascular reactivity, hemostatic factors and glucose and lipid profiles in patients with type 2 diabetes. METHODS: A prospective study was performed in 16 uncontrolled patients with diabetes previously treated with dietary intervention. The participants were randomized into metformin or glimepiride therapy groups. After four months, the patients were crossed over with no washout period to the alternative treatment for an additional four-month period on similar dosage schedules. The following variables were assessed before and after four months of each treatment: 1) fasting glycemia, insulin, catecholamines, lipid profiles and HbA1 levels; 2) t-PA and PAI-1 (antigen and activity), platelet aggregation and fibrinogen and plasminogen levels; and 3) the flow indices of the carotid and brachial arteries. In addition, at the end of each period, a 12-hour metabolic profile was obtained after fasting and every 2 hours thereafter. RESULTS: Both therapies resulted in similar decreases in fasting glucose, triglyceride and norepinephrine levels, and they increased the fibrinolytic factor plasminogen but decreased t-PA activity. Metformin caused lower insulin and pro-insulin levels and higher glucagon levels and increased systolic carotid diameter and blood flow. Neither metformin nor glimepiride affected endothelial-dependent or endothelial-independent vasodilation of the brachial artery. CONCLUSIONS: Glimepiride and metformin were effective in improving glucose and lipid profiles and norepinephrine levels. Metformin afforded more protection against macrovascular diabetes complications, increased systolic carotid artery diameter and total and systolic blood flow, and decreased insulin levels. As both therapies increased plasminogen levels but reduced t-PA activity, a coagulation process was likely still ongoing.

Retinopatia diabética / Diabetic retinopathy

A retinopatia é das complicacões mais comuns e está presente tanto no diabetes tipo 1 quanto no tipo 2, especialmente em pacientes com longo tempo de doenca e mau controle glicêmico. Quando culmina em perda visual é considerada trágica e constitui fator importante de morbidade de elevado impacto econômico, uma vez que a retinopatia diabética é a causa mais freqüente de cegueira adquirida. A fisiopatologia das alteracões microvasculares do tecido retiniano está relacionada à hiperglicemia crônica, que leva a alteracões circulatórias como a perda do tônus vascular, alteracão do fluxo sangüíneo, aumento da permeabilidade vascular e conseqüentemente extravasamentos e edemas e, por fim, obstrucão vascular que leva à neovascularizacão, com vasos frágeis que se rompem, levando a hemorragias e descolamento da retina. O controle metabólico e pressórico estritos podem retardar a progressão da retinopatia. Até o momento, nenhum agente farmacológico se mostrou eficaz em prevenir, retardar ou reverter a retinopatia diabética.O tratamento disponível no momento é a fotocoagulacão a laser de argônio e, em alguns casos, a vitrectomia. O sucesso do tratamento depende da deteccão precoce das lesões. Muitos estudos têm revelado mecanismos, assim como antagonistas importantes na evolucão da retinopatia.

Studies of the immediate postpartum diabetes remission and/or hypoglycemia after cesarean section in diabetic pregnancy

Five non-diabetic subjects, 5 gestational diabetics (GDM) treated with diet and 4 non-insulin dependent pregestational diabetics (NIDDM) treated with beef-pork insulin during their pregnancy, undergoing elective cesarean section (C-s), were given dextrose infusions without insulin for 7 hours (h) starting lh before the operation. Multiple blood samples were drawn up to 72 h after the C-s. The lowest glucose levels were observed at 3 3 or 6 h after surgery in all but two subjects. Plasma glucose below 2.75 mmol/l (49.5 mg/dl) were observed in 2 NIDDM patients. While in the non-diabetics and GDM the free (total) insulin and C-peptide values fell to very low levels, coinciding with the fall in plasma glucose, in the NIDDM there was a negative correlation between nadir glucose and free insulin levels with the progressive fall of antibody-bound insulin. In 3 out of NIDDM patients the antibodybound insulin fell to 57 to 73 per cent of the preoperative values. IGF-I/SmC, lower in the NIDDM, hGH immunoreactivity and hPL fell after C-s. The results suggest increased glucose utilization insulin-independent in the immediate postpartum in the non-diabetic pregnancy and GDM. However, in the NIDMM, in the presence of significant levels of free insulin, they tend to develop lower plasma glucose levels, sometimes hypoglycemia. Furthermore, lower IGF-I/Smc levels in the NIDDM in comparison to the non-diabetics and GDM would discard their role in the induction of hypoglycemia.