Type 2 Diabetes Mellitus and Alzheimer's Disease: from physiopathology to treatment implications.

Alzheimer's Disease (AD) is the most common cause of dementia worldwide. Type 2 Diabetes Mellitus (T2DM) is a disease characterized by insulin resistance (IR) and progressive ß cell failure, and affected individuals are at increased risk to develop several forms of cognitive dysfunction, including AD. Different mechanisms have already been identified linking visceral obesity, IR and AD. Insulin resistance is associated with a decrease in glucose uptake by neurons, an increase in Amyloid ß production and secretion, in the formation of senile plaques, and also in tau protein phosphorylation. Other mechanisms also include a decrease in Insulin Degrading Enzyme (IDE) activity and an increase in oxidative stress secondary to hyperglycemia. Taken together, these mechanisms suggest that drugs used to ameliorate hyperglycemia and IR may also have beneficial effects in diabetic patients with AD. Indeed, manuscripts investigating the effects of metformin, thiazolinediones, leptin, GLP-1 therapies, insulin and bariatric surgery in cognition and AD have been published with very promising results, and may indicate an alternative approach for these patients. This article is protected by copyright. All rights reserved.

Waist circumference is independently associated with liver steatosis and fibrosis in LMNA-related and unrelated Familial Partial Lipodystrophy women.

BACKGROUND: Lipodystrophies are a heterogeneous group of diseases characterized by the selective loss of subcutaneous adipose tissue and ectopic fat deposition in different organs, including the liver. This study aimed to determine the frequencies of liver steatosis (LS) and liver fibrosis (LF) in a sample of individuals with LMNA-related and unrelated Familial Partial Lipodystrophy. METHODS: This cross-sectional study included 17 women with LMNA-related FPLD and 15 women with unrelated FPLD. LS and LF were assessed using transient elastography (TE) with FibroScan®. Anthropometric and biochemical variables were included in a multiple linear regression analysis to identify the variables that were independently related to liver disease. RESULTS: Regarding the presence of LF, 22 (68.2%) women were classified as having non-significant fibrosis, and 10 (31.8%) were classified as having significant or severe fibrosis. Regarding LS, only six women (20.7%) were classified as having an absence of steatosis, and 23 (79.3%) had mild to severe steatosis. After multiple linear regression, waist circumference (but not age, body mass index, or waist-to-hip ratio) was found to be independently related to LS and LF. Among the biochemical variables, only triglyceride levels were independently related to LS but not LF. CONCLUSIONS: In women with FPLD, visceral fat accumulation appears to be the most important determinant of liver disease, including LF, rather than fat scarcity in the lower limbs.

Determinants of glycemic control in type 2 diabetes mellitus in Brazil: A sub-analysis of the longitudinal data from the BrazIian type 1 & 2 diabetes disease registry (BINDER).

BACKGROUND: Data on glycemic control and its determinants among Brazilian patients with type-2 diabetes (DM2) are scarce. The BrazIliaN Type 1 & 2 DiabetEs Disease Registry (BINDER) is a multicenter, longitudinal study, designed to investigate the glycemic control in a real-word scenario. METHODS: 1142 patients participated in the five visits of the BINDER study between April/2017 and October/2019. For each visit, glycemic control was assessed using the last measure available for HbA1c. Sociodemographic and anthropometric characteristics were also analyzed. RESULTS: At baseline, the median HbA1c level was 7.1% (4.1-15.0%); 259 (31.4%) participants had HbA1c ≤ 6.5% and 396 (48.2%) had HbA1c ≤ 7.0%. Younger age (p = 0.014), low educational level (p = 0.025) and the type of healthcare service (public sector; p = 0.0058) were independently associated with the elevated HbA1c. After 2 years, there were no statistically significant differences in HbA1c median values in relation to baseline. CONCLUSIONS: In this sample of DM2 patients, younger age, low educational level and being treated at the public service were associated with worse glycemic control. Over a 2-year follow-up, there was no significant change in the median HbA1c. These findings suggest that strategies are needed to improve glycemic control, especially in those treated in the public service.

Proposal of an obesity classification based on weight history: an official document by the Brazilian Society of Endocrinology and Metabolism (SBEM) and the Brazilian Society for the Study of Obesity and Metabolic Syndrome (ABESO).

Obesity is a chronic disease associated with impaired physical and mental health. A widespread view in the treatment of obesity is that the goal is to normalize the individual's body mass index (BMI). However, a modest weight loss (usually above 5%) is already associated with clinical improvement, while weight losses of 10%-15% bring even further benefits, independent from the final BMI. The percentage of weight reduction is accepted as a treatment goal since a greater decrease in weight is frequently difficult to achieve due to metabolic adaptation along with environmental and lifestyle factors. In this document, the Brazilian Society of Endocrinology and Metabolism (SBEM) and the Brazilian Society for the Study of Obesity and Metabolic Syndrome (ABESO) propose a new obesity classification based on the maximum weight attained in life (MWAL). In this classification, individuals losing a specific proportion of weight are classified as having "reduced" or "controlled" obesity. This simple classification - which is not intended to replace others but to serve as an adjuvant tool - could help disseminate the concept of clinical benefits derived from modest weight loss, allowing individuals with obesity and their health care professionals to focus on strategies for weight maintenance instead of further weight reduction. In future studies, this proposed classification can also be an important tool to evaluate possible differences in therapeutic outcomes between individuals with similar BMIs but different weight trajectories.

Impact of binge eating disorder in the psychopathological profile of obese women.

OBJECTIVE: Our objective was to evaluate the psychopathological profile of obese women with binge eating disorder (BED) using the Symptom Checklist-90 (SCL-90). METHODS: Two hundred twelve obese women who seek for weight loss treatment were sequentially selected to participate in the study. Binge eating disorder was diagnosed using the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Binge eating disorder severity was assessed using Binge Eating Scale. Depressive symptoms were assessed using Beck Depression Inventory. The psychopathological profile was assessed using the SCL-90. RESULTS: Binge eating disorder was diagnosed in 54 patients (26.6%). Obese patients with BED presented significant higher scores in all domains of SCL-90 (P < .05 for all) in comparison with obese patients without BED. A significant relationship was found among Binge Eating Scale, Beck Depression Inventory, and all domains of the SCL-90 (P < .05 for all). After linear regression, obsessivity-compulsivity (P = .03), interpersonal sensitivity (P = .0064), paranoid ideas (P = .03), and psychoticism (P = .01) were independently related to the severity of BED. CONCLUSION: Obese women with BED presented a more severe psychopathological profile than obese controls. Among all, obsessivity-compulsivity, interpersonal sensitivity, paranoid ideas, and psychoticism seem to be strongly linked to BED severity.

Post-prandial hypoglycemia after bariatric surgery: pharmacological treatment with verapamil and acarbose.

Postprandial hypoglycemia is a common complication of bariatric surgery. It is usually caused by late dumping syndrome, but a few other causes have already been described, including insulinoma and noninsulinoma pancreatogenous hypoglycemic syndrome (NIPHS). Considering that NIPHS is a recently described syndrome and is also very rare, therapeutic approaches are still not consensual. We report the case of a 26-year-old woman who was submitted to bariatric surgery and presented episodic postprandial hypoglycemic episodes after 16 months. Fasting C-peptide, insulin, and glucose were normal. Because of the possibility of NIPHS, clinical treatment was initiated with verapamil and acarbose, leading to a significant reduction of hypoglycemic episodes and also their severity. Surgery is the most common approach to NIPHS. However, in cases of mild or moderate symptoms, it is important to consider the possibility of pharmacological treatment. This approach may result, at least for some time, in an amelioration of symptoms without the need of an aggressive procedure.

Pancreatic fat deposition is increased and related to beta-cell function in women with familial partial lipodystrophy.

BACKGROUND: To study pancreatic fat deposition and beta-cell function in familial partial lipodystrophy (FPLD) patients. METHODS: In a cross-sectional study, eleven patients with FPLD, and eight healthy volunteers were matched for age and body mass index and studied at a referral center. Body composition was assessed using dual-energy X-ray absorptiometry and the Dixon method of magnetic resonance imaging was used to quantify pancreatic and liver fat. Fasting plasma glucose, insulin, leptin, lipids and homeostasis model assessment of insulin resistance values were measured, and an oral glucose tolerance test was performed. The insulinogenic index, Matsuda insulin sensitivity index and beta-cell disposition index were calculated. RESULTS: The FPLD group presented a higher waist-to-hip ratio and fat mass ratio and lower total, truncal and lower-limb fat masses. Pancreatic and liver fat contents (log transformed) were significantly higher in the FPLD group (5.26 ± 1.5 vs. 4.08 ± 0.64, p = 0.034 and 0.77 ± 0.50 vs. 0.41 ± 0.18, p = 0.056, respectively). Pancreatic fat was inversely related to the DI (r = - 0.53, p = 0.027) and HDL-cholesterol (r = - 0.63, p = 0.003) and directly related to WHR (r = 0.60; p = 0.009), HbA1c (r = 0.58; p = 0.01) and serum triglyceride (r = 0.48, p = 0.034). Higher triglyceride and lower HDL-cholesterol levels were observed in the FPLD group. CONCLUSIONS: This study demonstrated for the first time that pancreatic fat deposition is increased in FPLD. Moreover, an inverse relationship was demonstrated between pancreatic fat and beta-cell function. The findings of this study may be consistent with the expandability hypothesis and the twin cycle hypothesis.

Does binge eating disorder alter cortisol secretion in obese women?

It is still poorly determined whether the presence of Binge Eating Disorder (BED) would alter cortisol secretion in obese patients. We aimed at investigating levels of salivary cortisol (SC) in patients with and without BED. Forty seven (47) obese women between 30 and 65 years old were sequentially selected to participate in the study. The diagnosis of BED was assessed according to the Structured Clinical Interview for DSM-IV. Binge Eating Scale (BES) was used to assess binge severity. A trend toward a negative correlation was observed between SC and body mass index in the whole sample (p=0.06). The presence of BED was not associated with increased levels of SC. In women without BED, SC levels correlated inversely with BMI (p=0.01). On the other hand, in women with BED, SC levels correlated significantly with BES (p=0.01). Although obesity is associated with decreased levels of cortisol, this relationship may be lost in patients with BED. In patients with BED, binge eating severity may be a more relevant regulator of cortisol secretion than obesity itself.

Proposal of an obesity classification based on weight history: an official document by the Brazilian Society of Endocrinology and Metabolism (SBEM) and the Brazilian Society for the Study of Obesity and Metabolic Syndrome (ABESO)

ABSTRACT Obesity is a chronic disease associated with impaired physical and mental health. A widespread view in the treatment of obesity is that the goal is to normalize the individual's body mass index (BMI). However, a modest weight loss (usually above 5%) is already associated with clinical improvement, while weight losses of 10%-15% bring even further benefits, independent from the final BMI. The percentage of weight reduction is accepted as a treatment goal since a greater decrease in weight is frequently difficult to achieve due to metabolic adaptation along with environmental and lifestyle factors. In this document, the Brazilian Society of Endocrinology and Metabolism (SBEM) and the Brazilian Society for the Study of Obesity and Metabolic Syndrome (ABESO) propose a new obesity classification based on the maximum weight attained in life (MWAL). In this classification, individuals losing a specific proportion of weight are classified as having "reduced" or "controlled" obesity. This simple classification - which is not intended to replace others but to serve as an adjuvant tool - could help disseminate the concept of clinical benefits derived from modest weight loss, allowing individuals with obesity and their health care professionals to focus on strategies for weight maintenance instead of further weight reduction. In future studies, this proposed classification can also be an important tool to evaluate possible differences in therapeutic outcomes between individuals with similar BMIs but different weight trajectories.

Relation between insulin resistance and hematological parameters in a Brazilian sample.

It has already been demonstrated that insulin resistance (IR) is associated with the stimulation of erythroid progenitors and with increased levels of inflammation markers. Therefore, IR should also be associated with increased red blood cell (RBC) and white blood cell (WBC) count. The aim of this study is to demonstrate that IR is independently associated with altered hematological parameters in a Brazilian sample. We analyzed laboratorial exams from 925 subjects. All data on hematological parameters, insulin resistance (Homeostasis Model Assessment [HOMA]) and lipid levels were included in the analysis. Demographic information included age and gender. HOMA correlated positively with RBC (r= 0.17, p< 0.001), plasma hemoglobin concentrations (r= 0.14, p< 0.001), hematocrit value (r= 0.15, p< 0.001) and WBC (r= 0.17, p< 0.01). Subjects in the upper quartile of IR had higher levels of plasma glucose, fasting insulin, triglycerides, hematocrit, hemoglobin, RBC and WBC count than those in the lower quartile. In conclusion, IR seems to be associated with alterations in several hematological parameters. These hematological alterations may be considered an indirect feature of the IR syndrome.

[Lipid profile of patients with increased risk for cardiovascular events in daily clinical practice]. / Perfil lipídico de pacientes com alto risco para eventos cardiovasculares na prática clínica diária.

Although there are specific guidelines regarding the treatment of dyslipidemia in highly risk patients, these recommendations are usually inadequately followed. The aim of this study is to investigate risk factors in patients with increased cardiovascular risk currently treated in Brazil and Venezuela. Medical charts of 412 patients were selected in 4 institutions. Patients were divided into groups according to the use of lipid-lowering drugs (LLD), particularly statins. Patients who did not use LLD showed higher levels of total cholesterol (p< 0.001), LDL cholesterol (p< 0,001) and HDL cholesterol (p< 0.001), besides lower levels of triglycerides (p< 0.001). The use of statins was associated with a decrease in levels of total cholesterol (from 251.0 +/- 40.0 to 196.0 +/- 46.0), LDL cholesterol (from 168.0 +/- 36.0 to 116.0 +/- 39.0), HDL cholesterol (from 51.0 +/- 46.0 to 46.0 +/- 12.0) and triglycerides (from 181.0 +/- 120.0 to 160.0 +/-79.0). Finally, only a small percentage of patients, even those under treatment with LLD, showed cholesterol levels according to currently available guidelines. Therefore, although the guidelines for the treatment of dyslipidemia are widely known, only a small percentage of patients achieve adequate levels of cholesterol. It is necessary to decrease lipid levels of these patients by increasing the dose of the statins or using a second drug.

[Hyperparathyroidism associated with hypophosphatemic osteomalacia: case report and review of the literature]. / Hiperparatireoidismo associado à osteomalacia hipofosfatêmica do adulto: relato de caso e revisão da literatura.

Adult-onset hypophosphatemic osteomalacia is a rare disease characterized by hypophosphatemia, increased levels of alkaline phosphatase and decreased bone mass. Oral supplementation with phosphate and vitamin D is the main treatment and, in cases of oncogenic osteomalacia, tumor resection is mandatory. We report the case of a patient with hypophosphatemic osteomalacia of an unknown cause. Despite extensive search, no tumor was found. The patient was treated with phosphate for a long period and developed tertiary hyperparathyroidism. Serum PTH levels did not return to normal after surgical excision of three parathyroids and the patient refused to continue clinical investigation and treatment. After ten years absent from the hospital, during which medications were used irregularly, she was admitted with multiple fractures and respiratory insufficiency caused by severe thoracic deformities, and died. The authors discuss the relationship between osteomalacia and hyperparathyroidism and the aggressive course of the disease.

Impact of a 6-month treatment with intragastric balloon on body composition and psychopathological profile in obese individuals with metabolic syndrome.

BACKGROUND: The aim of this study was to investigate the effects of a 6-month treatment with intragastric balloon (IGB) on body composition and depressive/anxiety symptoms in obese individuals with metabolic syndrome (MS). METHODS: Fifty patients (aged 18-50 years) with obesity and MS were selected for treatment with IGB for 6 months. Body composition was verified with dual-energy X-ray absorptiometry (DXA) at baseline and right after IGB removal. Anxiety/depressive symptoms were assessed with the Beck Depression Inventory (BDI) and the hospital anxiety and depression scale (HADS) at baseline and after 6 months of treatment. RESULTS: In total, 39 patients completed the study. After 6 months, there were significant decreases in weight (11.7 ± 9.6 kg, p < 0.0001) and waist circumference (9.3 ± 8.2 cm, p < 0.0001). Weight loss was also demonstrated by DXA and corresponded to decreases of 3.0 ± 3.4% in body fat percentage, 7.53 ± 7.62 kg in total body fat, and 3.70 ± 4.89 kg in lean body mass (p < 0.001 for all comparisons). Depressive symptoms scores decreased by a mean of 4.57 ± 10.6 points when assessed with the BDI (p = 0.002) and 1.82 ± 5.16 points when assessed with the HADS-Depression (p = 0.0345). Anxiety symptoms scores decreased by a mean of 1.84 ± 4.04 points when determined with the HADS-anxiety (p = 0.0066). The decrease in body fat percentage was the parameter that best correlated with improvements in depressive (p = 0.008) and anxiety symptoms (p = 0.014). CONCLUSIONS: In obese individuals with MS, fat mass reduction was associated with short-term improvements in depressive and anxiety symptoms. Trial Registration Registered at ClinicalTrials.gov, NCT01598233.

Treatment of obese adolescents with sibutramine: a randomized, double-blind, controlled study.

Adolescent obesity is becoming a health problem in both developed and developing countries. Antiobesity drug therapy is not currently indicated for the treatment of adolescent obesity and remains investigational at this time. The aim of this study was to determine the efficacy and safety of sibutramine in obese adolescents. A randomized, double-blind, placebo-controlled trial, enrolling 60 adolescents, aged 14-17 yr, for 6 months was conducted. In the first month, all patients received placebo and a hypocaloric diet plus exercise orientation. For the next 6 months, participants received either sibutramine or placebo. Patients assigned to sibutramine group lost an average of 10.3 +/- 6.6 kg, and patients in placebo group lost 2.4 +/- 2.5 kg (P < 0.001). The mean body mass index reduction was significantly greater in the sibutramine group (3.6 +/- 2.5 kg/m(2)) than in the placebo group (0.9 +/- 0.9 kg/m(2); P < 0.001). No participant withdrew because of adverse events, and no difference in blood pressure or heart rate was noted between groups. There were no changes in echocardiographic parameters. In conclusion, sibutramine plus diet and exercise induced significantly more weight loss in obese adolescents.

[Translation into Portuguese and assessment of the reliability of a scale for the diagnosis of diabetic distal polyneuropathy]. / Tradução para o português e avaliação da confiabilidade de uma escala para diagnóstico da polineuropatia distal diabética.

The aim of this study was to translate into Portuguese and to assess the reliability of an instrument for the diagnosis of diabetic distal polyneuropathy (DPN). The process for translation and adaptation into Portuguese of the Neuropathy Symptom Score (NSS) and the Neuropathy Disability Score (NDS) was performed following internationally standardized procedures. The instruments were applied by 2 raters in 57 consecutive subjects. Spearman correlation was used to evaluate the reliability and Cronbachs' alpha to evaluate the internal consistency of the items. Both, ECN and ESN, showed a good reliability (r= 0.77, p< 0.0001 and r= 0.76, p< 0.0001, respectively). ESN showed a good internal consistency (alpha= 0.74). The diagnosis of DPN, defined as the combination of the two scores (ECN+ESN) also showed a good reliability (r= 0.63, p< 0.0001). The Portuguese versions of the ESN and the ECN seem to be adequate for the diagnosis of DPN in this population.

[Evaluation of the sibutramine effect on satiety with a visual analogue scale in obese adolescents]. / Avaliação do efeito da sibutramina sobre a saciedade por escala visual analógica em adolescentes obesos.

Initially used to measure algic symptoms, visual analogue scales (VAS) can also be useful for the evaluation of satiety. The antiobesity agent sibutramine, unlike anorectic agents, decreases food intake mainly by stimulating satiety. To evaluate the effect of sibutramine on satiety, we used a VAS in obese adolescents participating in a double-blind, randomized trial comparing 10 mg of sibutramine to placebo. Each patient received 13 scales to be checked at hourly intervals, in a single day, from 9 am to 9 pm. A 500 kcal deficit diet was divided into 3 meals, with previously fixed times: 9:30 h, 12:30 h, 18:30 h. Using the scores obtained from each scale, a line graph was designed to represent the average satiety score throughout the day. Comparing the area under the curve for the 2 groups, we found 4.609 +/- 1.309 for the group treated with sibutramine and 4.141 +/- 1.432 for the placebo group, not reaching statistical significance (p= NS). Therefore, sibutramine does not seem do have an effect on satiety of obese adolescents, at least when satiety is evaluated by a VAS.

Is cognitive impairment associated with the presence and severity of peripheral neuropathy in patients with type 2 diabetes mellitus?

BACKGROUND: Peripheral Diabetic Neuropathy (PDN) and cognitive impairment are complications of Diabetes Mellitus (DM) that seem to share several underlying mechanisms. The aim of this study was to investigate whether diabetic patients would have worse cognitive function than non diabetic individuals and within diabetic patients, whether those with PDN would present an even more significant cognitive impairment. FINDINGS: Ninety four (94) outpatients with Type 2 DM were sequentially evaluated. Also, Fifty four (54) healthy individuals were sequentially selected to match the diabetic group. For the assessment of neuropathy, Portuguese versions of the Neuropathy Disability Score (NDS) and Neuropathy Symptom Score (NSS) were used. Global cognitive function was assessed by using the Portuguese Version of the Mini-Mental State Examination (MMSE), Trail Making Tests A and B and Verbal Fluency Test. Significantly lower scores were found in the Type 2 DM group in comparison to control group in the MMSE (25.7 [16-30] vs 27.6 [19-30]; p <0.001). Within T2DM group, forty five (45) patients were diagnosed with PDN. No differences were found between patients with and without PDN in all cognitive tests (p >0.05 in all comparison). No correlation was also found among NSS, NDS and any of the cognitive tests. CONCLUSION: Although diabetic patients do have a worse cognitive function, this impairment does not seem to be related to the presence and/or severity of PDN.