Marcello Casaccia Bertoluci

Saccharin and aspartame, compared with sucrose, induce greater weight gain in adult Wistar rats, at similar total caloric intake levels

It has been suggested that the use of nonnutritive sweeteners (NNSs) can lead to weight gain, but evidence regarding their real effect in body weight and satiety is still inconclusive. Using a rat model, the present study compares the effect of saccharin and aspartame to sucrose in body weight gain and in caloric intake. Twenty-nine male Wistar rats received plain yogurt sweetened with 20% sucrose, 0.3% sodium saccharin or 0.4% aspartame, in addition to chow and water ad libitum, while physical activity was restrained. Measurements of cumulative body weight gain, total caloric intake, caloric intake of chow and caloric intake of sweetened yogurt were performed weekly for 12 weeks. Results showed that addition of either saccharin or aspartame to yogurt resulted in increased weight gain compared to addition of sucrose, however total caloric intake was similar among groups. In conclusion, greater weight gain was promoted by the use of saccharin or aspartame, compared with sucrose, and this weight gain was unrelated to caloric intake. We speculate that a decrease in energy expenditure or increase in fluid retention might be involved.

Transforming growth factor-beta in the development of rat diabetic nephropathy. A 10-month study with insulin-treated rats.

We investigated the intrarenal distribution of transforming growth factor-beta 1 (TGF-beta 1) protein and the TGF-beta 1 mRNA levels in the glomeruli and renal cortex of Wistar rats with streptozotocin-induced diabetes before and after the onset of diabetic nephropathy. Monthly urinary albumin excretion, glomerular filtration rate, glomerular volume, renal histology and immunohistochemical reaction for type-I collagen were also studied. The results showed progressively higher glomerular immunohistochemical TGF-beta 1 staining in rats with a diabetes duration of 24 and 40 weeks which was correlated with albuminuria (r = 0.905, p < 0.01) and was temporally associated with the appearance of glomerular deposition of total and type-I collagen. The glomerular content of TGF-beta 1 mRNA was higher in rats diabetic for 20 weeks while lower cortical RNA-TGF-beta 1 levels were found in rats with a diabetes duration of 1-40 weeks. These data suggest that this polypeptide may be an important mediator of diabetic glomerulosclerosis.

Endothelial Dysfunction Is Related to Poor Glycemic Control in Adolescents with Type 1 Diabetes under 5 Years of Disease: Evidence of Metabolic Memory

CONTEXT The relation between endothelial dysfunction (ED), glycemic control, and early type I diabetes mellitus (T1DM) is unclear. OBJECTIVE The objective of the study was to evaluate the association of ED, glycemic control, and the duration of diabetes in T1DM. DESIGN This was a cross-sectional study. SETTING The study was conducted at a public outpatient clinic. PATIENTS Fifty-seven T1DM adolescents and 10 healthy age-matched controls participated in the study. INTERVENTION There were no interventions. METHODS AND OUTCOME MEASURES Endothelial function (ED) was evaluated by flow-mediated dilation (FMD) in the brachial artery after reactive hyperemia. Biochemical data, including HbA1c (glycohemoglobin), high-sensitivity C-reactive protein, lipids, and urinary albumin excretion were collected. Means of four HbA1c values collected at 3-month intervals in the first and second year before FMD analyses were obtained. RESULTS Mean FMD was decreased in T1DM compared with controls (P = 0.023), independent of age, smoking, hypertension, or dyslipidemia. Twenty-eight of 57 T1DM patients enrolled (49%) had ED. FMD was decreased in microalbuminuric (4.1%) compared with normoalbuminuric patients (10.1%, P = 0.01) and controls (14.6%, P < 0.001). FMD correlated inversely with mean second-year HbA1c (r = -0.426, P = 0.02), particularly in patients with less than 5 yr of T1DM (r = -0.61, P = 0.004). In these patients, high-sensitivity C-reactive protein was strongly correlated with mean first-year HbA1c (r = -0.66, P = 0.0003). In patients with more than 5 yr of T1DM, we found no significant correlations between ED and glycemic control. CONCLUSIONS Endothelial dysfunction is common in T1DM adolescents with less than 5 yr of disease. It is associated with duration of disease, microalbuminuria, and mean second-year HbA1c but not with mean first-year HbA1c. These data support the metabolic memory hypothesis.

Serotonina e controle hipotalâmico da fome : uma revisão

This paper reviews involvement of the serotonergic system in the control of food intake and satiety. It is of great interest to understand the relevance of this system for physiological control of energy balance and obesity. Over 35 years of research suggest that serotonin (5-HT) plays an important role in satiety. Thus, the serotonergic system has been a viable target for weight control. The 5-HT has control over hunger and satiety through different receptors with distinct functions. The 5-HT2C receptor may be more important in the relationship between food intake and energy balance. This review will discuss the mechanisms of the serotonergic system involved in the control of food intake and satiety.

Impact of renal denervation on renal content of GLUT1, albuminuria and urinary TGF-β1 in streptozotocin-induced diabetic rats

In long-term diabetes mellitus, the progression of nephropathy has been related to the occurrence of autonomic neuropathy. This study was designed to evaluate the effects of bilateral denervation of the kidneys of streptozotocin-diabetic rats, an experimental model that presents diabetic nephropathy with increased abundance of cortical GLUT1 in the kidney and increased urinary excretion of albumin and transforming growth factor-beta1 (TGF-beta1). Twenty-four-hour urinary TGF-beta1 (ELISA), urinary albumin (electroimmunoassay) and GLUT1 protein levels (Western blotting) in the renal cortex and medulla were evaluated in diabetic (n=13) and control (n=13) rats 45 days after streptozotocin injection, submitted or not to surgical renal denervation. Evaluations were performed 15 days after the surgery. The effects of renal denervation were confirmed by intra-renal decrease of norepinephrine levels. Mean arterial pressure did not differ between diabetic and control rats, whether they underwent renal denervation or not. Renal denervation increased cortical (6905+/-287, 3506+/-193, 4144+/-246 and 5204+/-516 AU in renal-denervated controls, controls, renal-denervated diabetics and diabetics, respectively) and medullar GLUT1 protein in control rats, but reverted the cortical GLUT1 protein rise determined by diabetes. Although kidney denervation in diabetic rats induced a decrease in cortical GLUT1 abundance toward normal levels, these levels did not reach those of normal animals. However, renal denervation did not determine any changes in urinary albumin and urinary TGF-beta1 in both diabetic (127.3+/-12 microg/24 h and 111.8+/-24 ng mg(-1) creatinine, respectively) and control rats (45.9+/-3 microg/24 h and 13.4+/-4 ng mg(-1) creatinine, respectively). In conclusion, early-phase renal denervation in streptozotocin-diabetic rats produces a normalisation of previously elevated cortical GLUT1 protein content, but is not enough for reverting the increased urinary TGF-beta1 and albuminuria of diabetes.

Insulin resistance and triglyceride/HDLc index are associated with coronary artery disease

BackgroundInsulin-resistance is associated with cardiovascular disease but it is not used as a marker for disease in clinical practice.AimsTo study the association between the homeostatic model assessment (HOMA-IR) and triglyceride/HDLc ratio (TG/HDLc) with the presence of coronary artery disease in patients submitted to cardiac catheterization.MethodsIn a cross-sectional study, 131 patients (57.0 ± 10 years-old, 51.5% men) underwent clinical, laboratory and angiographic evaluation and were classified as No CAD (absence of coronary artery disease) or CAD (stenosis of more than 30% in at least one major coronary artery).ResultsPrevalence of coronary artery disease was 56.7%. HOMA-IR and TG/HDLc index were higher in the CAD vs No CAD group, respectively: HOMA-IR: 3.19 (1.70-5.62) vs. 2.33 (1.44-4.06), p = 0.015 and TG/HDLc: 3.20 (2.38-5.59) vs. 2.80 (1.98-4.59) p = 0.045) - median (p25-75). After a ROC curve analysis, cut-off values were selected based on the best positive predictive value for each variable: HOMA-IR = 6.0, TG/HDLc = 8.5 and [HOMA-IR×TG/HDLc] = 28. Positive predictive value for coronary artery disease for HOMA-IR>6.0 was 82.6%, for TG/HDLc>8.5 was 85.7% and for [HOMA-IR×TG/HDLc]>28 was 88.0%. Adjusted relative risk (age, gender, diabetes, body mass index, systolic blood pressure) for the presence of coronary artery disease was: for HOMA-IR>6.0, 1.47 (95.CI: 1.06-2.04, p = 0.027), for TG/HDLc>8.5, 1.46 (95% CI:1.07-1.98), p = 0.015) and for [HOMA-IR × TG/HDLc] >28, 1.64 (95%CI: 1.28-2.09), p < 0.001).ConclusionsIncreased HOMA-IR, TG/HDLc and their product are positively associated with angiographic coronary artery disease, and may be useful for risk stratification as a high-specificity test for coronary artery disease.

Microalbuminuria is associated with impaired arterial and venous endothelium-dependent vasodilation in patients with Type 2 diabetes

Background: Microalbuminuria in Type 2 diabetes is associated with arterial endothelial dysfunction, but the venous bed was never evaluated. Aim: To study the endothelial function in the venous and arterial bed in patients with Type 2 diabetes with normoalbuminuria or microalbuminuria. Material and methods: We evaluated 28 patients with Type 2 diabetes, glycated hemoglobin (HbA1c) <7.5%, who were classified as normo- (albuminuria <30 mg/24 h; no.=16) or microalbuminuric (albuminuria 30–300 mg/24 h; no.=12). Venous and arterial endothelial function were assessed by the dorsal hand vein technique (venodilation by acetylcholine) and brachial artery flow-mediated vasodilation, respectively. Results: Patients were normotensive (systolic arterial pressure: 131.1±10.6 mmHg) and on good metabolic control (HbA1c: 6.6±0.6%). Microalbuminuric patients presented impaired venous (32.9±17.4 vs 59.3±26.5%; p=0.004) and arterial vasodilation (1.8±0.9 vs 5.1±2.4; p<0.001), as compared to normoalbuminuric patients. There was a negative correlation between acetylcholine-induced venodilation and albuminuria (r=−0.62; p<0.001) and HbA1c (r=−0.41; p=0.032). The same was observed between flow-mediated arterial vasodilation and albuminuria (r=−0.49; p=0.007) and HbA1c (r=−0.44; p=0.019). Venous and arterial vasodilation was positively correlated (r=0.50; p=0.007). Conclusions: Both venous and arterial endothelial function are impaired in Type 2 microalbuminuric diabetics, in spite of good metabolic control, suggesting that other factors are involved in its pathogenesis.

[Serotonin and hypothalamic control of hunger: a review].

This paper reviews involvement of the serotonergic system in the control of food intake and satiety. It is of great interest to understand the relevance of this system for physiological control of energy balance and obesity. Over 35 years of research suggest that serotonin (5-HT) plays an important role in satiety. Thus, the serotonergic system has been a viable target for weight control. The 5-HT has control over hunger and satiety through different receptors with distinct functions. The 5-HT2C receptor may be more important in the relationship between food intake and energy balance. This review will discuss the mechanisms of the serotonergic system involved in the control of food intake and satiety.

'Correction:' Serum transforming growth factor beta-1 (TGF-beta-1) levels in diabetic patients are not associated with pre-existent coronary artery disease

BackgroundThe association between TGF-β1 levels and long-term major adverse cardiovascular events (MACE) in patients with coronary artery disease (CAD) is controversial. No study specifically addressed patients with CAD and diabetes mellitus (DM). The association between TGF-β1 levels and long-term major adverse cardiovascular events (MACE) in patients with coronary artery disease (CAD) is controversial. No study specifically addressed patients with CAD and diabetes mellitus (DM).MethodsPatients (n = 135, 30–80 years) referred for coronary angiography were submitted to clinical and laboratory evaluation, and the coronary angiograms were evaluated by two operators blinded to clinical characteristics. CAD was defined as the presence of a 70% stenosis in one major coronary artery, and DM was characterized as a fasting glycemia > 126 mg/dl or known diabetics (personal history of diabetes or previous use of anti-hyperglycemic drugs or insulin). Based on these criteria, study patients were classified into four groups: no DM and no CAD (controls, C n = 61), DM without CAD (D n = 23), CAD without DM (C-CAD n = 28), and CAD with DM (D-CAD n = 23). Baseline differences between the 4 groups were evaluated by the χ2 test for trend (categorical variables) and by ANOVA (continuous variables, post-hoc Tukey). Patients were then followed-up during two years for the occurrence of MACE (cardiac death, stroke, myocardial infarction or myocardial revascularization). The association of candidate variables with the occurrence of 2-year MACE was assessed by univariate analysis.ResultsThe mean age was 58.2 ± 0.9 years, and 51% were men. Patients with CAD had a higher mean age (p = 0.011) and a higher percentage were male (p = 0.040). There were no significant baseline differences between the 4 groups regarding hypertension, smoking status, blood pressure levels, lipid levels or inflammatory markers. TGF-β1 was similar between patients with or without CAD or DM (35.1 ×/÷ 1.3, 33.6 ×/÷ 1.6, 33.9 ×/÷ 1.4 and 31.8 ×/÷ 1.4 ng/ml in C, D, C-CAD and D-CAD, respectively, p = 0.547). In the 2-year follow-ip, independent predictors of 2-year MACE were age (p = 0.007), C-reactive protein (p = 0.048) and systolic blood pressure (p = 0.008), but not TGF-β1.ConclusionSerum TGF-β1 was not associated with CAD or MACE occurrence in patients with or without DM.

Intensity-related exercise albuminuria in insulin dependent diabetic patients

Normoalbuminuric insulin-dependent diabetic (IDDM) patients may present higher rates of urinary albumin excretion after submaximal exercise at a standard intensity. To evaluate whether the urinary albumin excretion of IDDM patients is increased after maximal and submaximal exercise when exercise intensities are adjusted according to individual lactate thresholds, 16 normoalbuminuric IDDM patients (mean time from diagnosis 8 years) and 13 normal controls exercised for 20 min at intensities corresponding to 90% of the first and second lactate thresholds and to maximal tolerance on different days. Urinary albumin excretion, blood lactate concentration, heart rate and blood pressure were measured. Metabolic and cardiovascular responses to submaximal and maximal exercise were similar for patients and controls. After exercise at 90% of the first lactate threshold neither patients or controls demonstrated significant changes in urinary albumin excretion. After exercise at 90% of the second lactate threshold both patients and controls demonstrated a similar increase in urinary albumin excretion. After maximal exercise both patients and controls demonstrated marked and similar elevation in the urinary albumin excretion. There was a significant correlation (r = 0.74, P < 0.001) between blood lactate levels at the end of exercise and the decimal logarithm of post-exercise urinary albumin excretion of the diabetic patients. Thus, when exercise intensities are adjusted for lactate thresholds, normoalbuminuric IDDM patients present normal intensity-related urinary albumin excretion during exercise. These data suggest that previously observed differences in exercise induced albuminuria in IDDM patients might be related to inappropriate standardization of submaximal exercise intensities.