O receptor sensor do cálcio (CASR) desempenha um importante papel na manutenção da concentração plasmática do cálcio. Desde a sua descrição, mais de 200 mutações foram descritas podendo levar à perda ou ao ganho de função, resultando em situações de hiper ou hipocalcemia, respectivamente. Mutações inativadoras estão associadas à hipercalcemia hipocalciúrica familiar (HHF) e ao hiperparatireoidismo neonatal grave (HPTNG), enquanto que mutações ativadoras estão associadas à hipocalcemia autossômica dominante (HAD) e à Síndrome de Bartter tipo V. O objetivo deste estudo foi realizar o diagnóstico molecular, por meio da análise do gene CASR, em pacientes com HPTNG, HHF, hipocalcemia com PTH inapropriadamente normal ou baixo e hipoparatireoidismo idiopático com hipercalciúria na vigência de tratamento. Para cada criança (n = 2) com diagnóstico clínico e laboratorial de HPTNG, uma mutação \"nonsense\" em homozigose foi identificada na região codificadora do CASR (p.E519X e p.R544X). O estudo molecular dos pais das crianças mostrou tratar-se de casos herdados caracterizando-os como indivíduos com HHF e possibilitou o aconselhamento genético para estas famílias. Mutações pontuais em heterozigose na região codificadora do CASR (p.R25X, p.R69H, p.T627I) foram detectadas em três dos quatro pacientes selecionados com diagnóstico inicial de hiperparatireoidismo primário e bioquímica compatível com hipercalcemia hipocalciúrica. Estes achados constituem a base molecular da HHF e permitiram o rastreamento de outros casos de HHF nas respectivas famílias com impacto na abordagem terapêutica dos mesmos. Na paciente em que não foi detectada nenhuma mutação na região codificadora do CASR, o estudo prosseguiu com a pesquisa de alterações no número de cópias gênicas e de mutações nas regiões promotoras P1 e P2 como possíveis causas do fenótipo em questão. O resultado destas abordagens foi normal. Dos quatro pacientes selecionados com quadro de hipoparatireoidismo idiopático e hipercalciúria na vigência de tratamento, em apenas uma, a causa molecular foi definida por mutação \"missense\" em heterozigose na região codificadora do CASR (p.E767K) repercutindo positivamente no seu tratamento. Nos demais casos (n = 3), a pesquisa de alterações no número de cópias gênicas e de mutações nas regiões promotoras P1 e P2 também resultou normal. / The calcium sensing receptor (CASR) plays an important role in maintaining the plasma concentration of calcium. From its first description, more than 200 mutations have been described leading to loss or gain of function, resulting in conditions of either hyper or hypocalcemia, respectively. Inactivating mutations are associated with familial hypocalciuric hypercalcemia (FHH) and neonatal severe hyperparathyroidism (NSHPT), whereas activating mutations are associated with autosomal dominant hypocalcemia (ADH) and type V Bartter\'s syndrome. The aim of this study was to perform the molecular diagnosis, by analyzing the CASR gene, in patients with NSHPT, FHH, hypocalcemia with inappropriately normal or low PTH and idiopathic hypoparathyroidism with hypercalciuria during treatment. In every child (n = 2) with clinical and laboratory diagnosis of NSHPT, a nonsense mutation in homozygosity was identified in the coding region of the CASR (p.E519X and p.R544X). The molecular analysis of the child\'s parents showed that they were inherited cases qualifying them as individuals with FHH and it enabled a genetic counseling for these families. Point mutations in heterozygosity in the coding region of the CASR (p.R25X, p.R69H, p.T627I) have been detected in three out of the four selected patients with an initial diagnosis of primary hyperparathyroidism and biochemistry compatible with hypocalciuric hipercalcemia. These findings are the molecular basis of FHH and allowed the screening of other FHH cases in these families impacting on their therapeutic approach. In patients where no mutation in the coding region of the CASR was detected, the study went on researching for changes in the number of gene copies and mutations in P1 and P2 promoter regions as possible causes to the phenotype in question. The result of these approaches has been normal. The molecular cause has been defined as missense mutation in heterozygosis in the coding region of the CASR (p.E767K) in only one out of the four selected patients with idiopathic hypoparathyroidism and hypercalciuria during treatment, with a positive impact on her treatment. In the other cases (n = 3), the search for changes in the number of gene copies and mutations in the P1 and P2 promoter regions was normal.

Abstract not available

[Formulae and special characters can only be approximated here. Please see the pdf version of the abstract for an accurate reproduction.] Atherosclerosis is a common degenerative disease in which the clinical manifestations are often through stroke or myocardial infarction. Some of the established risk factors for atherosclerosis include elevated plasma low-density lipoprotein (LDL)-cholesterol levels, obesity, diabetes mellitus (DM) and cigarette smoking. Of the risk factors, an elevation in plasma LDL is one of the most established and the most researched. This is partly a consequence of the deposition of cholesterol within arterial intima being a crucial step in the progression of atherosclerosis, combined with the finding that LDL particles are a major transporter of cholesterol in circulation. Recently there is increasing evidence showing a role of the other major transporter of cholesterol in circulation, chylomicron remnants, in the progression of atherosclerosis. The notion of atherosclerosis as a postprandial phenomenon has been further substantiated by the emergence of evidence showing a direct role of chylomicron remnants in arterial cholesterol deposition. Based on evidence that chylomicron remnants are proatherogenic, the suggestion arises that accumulation of postprandial lipoproteins in plasma may add another dimension of risk to the development of coronary artery disease (CAD). This thesis tests the general hypothesis that individuals with or at high risk of CAD have postprandial dyslipidaemia and that this metabolic abnormality is correctable with a class of lipid-lowering drugs called statins. To test the hypothesis, clinical studies were conducted in normolipidaemic CAD patients, heterozygous familial hypercholesterolaemia (FH) and postmenopausal women with type 2 DM. Determination of postprandial dyslipidaemia by comparison with control populations were conducted initially in each patient group (Studies 1, 3 and 5), followed by intervention studies investigating possible modulation of the dyslipidaemia with a statin (Studies 2, 4 and 6). Six observation statements based on case-control comparisons of postprandial lipaemia in patients with or at risk of CAD and the effects of statins on postprandial dyslipidaemia in the patient groups were derived from the general hypothesis. The observation statements were examined in the individual studies described below. Postprandial lipoprotein metabolism was assessed using a number of methods. For comparison of postprandial lipaemia in Studies 1 and 2, a classic oral fat challenge was utilised. As markers of chylomicrons and chylomicron remnants, retinyl palmitate and triglyceride were measured postprandially as well as apolipoprotein (apo) B48 concentrations, a specific marker of intestinal lipoproteins. ApoB48 was also measured in the fasting state and found to predict the postprandial responses of retinyl palmitate, triglyceride and apoB48. This suggested that fasting measurement of apoB48 could be used as a simple indicator of postprandial dyslipidaemia. Consequently for Studies 3 - 6, fasting apoB48 measurements were used as primary markers of postprandial dyslipidaemia. Other markers for chylomicrons and their remnants utilised were fasting plasma concentrations of remnant-like particle-cholesterol (RLP-C) and apoC-III. As well as these static markers, chylomicron remnant catabolism was measured using a stable isotope breath test. The breath test involves the intravenous injection of a chylomicron remnant-like emulsion labelled with ¹³C-oleate and measurement of enriched ¹³CO2 in expired breath by isotope ratio mass spectrometry. The fractional catabolic rate (FCR) of the injected emulsion was subsequently calculated using multi-compartmental modeling (SAAM II). The studies are presented in this thesis as published and unpublished works. In Study 1, postprandial lipoprotein metabolism was compared between 18 normolipidaemic CAD patients (cholesterol 4.54 ± 0.12 mmol/L, triglyceride 1.09 ± 0.16) with 13 asymptomatic healthy controls using an oral fat challenge. Normolipidaemic CAD patients had higher postprandial area-under-curve (AUC) for triglyceride (+34%, p=0.019), retinyl palmitate (+74%, p=0.032) and apoB48 (+36%, p<0.001). Fasting apoB48 was also higher (+41%, p=0.001) and found to correlate significantly with AUC of triglyceride (p=0.017), retinyl palmitate (p=0.001) and apoB48 (p<0.001). The data suggest that normolipidaemic CAD patients have increased concentrations of intestinal lipoproteins in the fasting and postprandial state. In addition to these findings, significant correlations of fasting apoB48 with postprandial markers (p<0.02) suggests the fasting marker to be a simpler surrogate marker for the degree of total postprandial lipaemia. Study 2 investigated the effect of atorvastatin treatment on postprandial dyslipidaemia found in the 18 near-normolipidaemic CAD patients from Study 1. The trial was conducted in a randomised, placebo-controlled design, using oral fat challenges before and after 12-weeks atorvastatin/placebo treatment. Compared with the placebo group, atorvastatin decreased the total postprandial AUC for iii triglyceride (-22%, p=0.05) and apoB48 (-34%, p=0.013). Fasting markers of apoB48 (-35%, p=0.019) and RLP-C (-36%, p=0.032) also decreased significantly. Atorvastatin was also found to increase LDL-receptor activity by +218% (p<0.001) as reflected in binding studies. The data suggest atorvastatin reduces the fasting levels of intestinal lipoproteins as well as total postprandial lipaemia, but without acute dynamic changes in postprandial lipaemia. The reduction in fasting and total postprandial lipoprotein levels could be partly attributed to an increase in LDL-receptor mediated removal from circulation. In Study 3, postprandial lipaemia was compared in 15 heterozygous FH patients with 15 healthy controls. FH patients had higher fasting concentrations of apoB48 (+56%, p<0.001) and RLP-C (+48%, p=0.003). The elevation in these fasting markers of chylomicrons and their remnants suggests FH patients have postprandial dyslipidaemia due to an accumulation of these particles in plasma. Study 4 examined the effects of long- (> 6 months) and short-term (4 weeks) simvastatin treatment on modulating postprandial dyslipidaemia found in the 15 FH patients from Study 3. Short- and long-term simvastatin treatment decreased the fasting concentrations of apoB48 (-29% and 15% respectively, p<0.05) and RLP-C (both -38%, p<0.001), but did not significantly alter the FCR of the injected chylomicron remnant-like emulsion. The data suggest that in heterozygous FH both long- and short-term simvastatin treatments decrease the fasting markers of postprandial lipoproteins by mechanisms that may not be mediated via processes differentiated by the 13CO2 breath test. This implies that the effect on postprandial lipaemia may be from a decrease in production and/or a possible increase in catabolism of triglyceride-rich lipoproteins (TRLs). In Study 5, postprandial lipaemia was compared in 24 postmenopausal women age and body mass index matched with 14 postmenopausal women with type 2 DM. Postmenopausal diabetic women were found to have higher fasting concentrations of apoB48 (+21%, p=0.021) and apoC-III (+16%, p=0.042) as well as lower FCR of the chylomicron remnant-like emulsion (-50%, p<0.001). The data suggest that postmenopausal diabetic women have postprandial dyslipidaemia, and that this is due to delayed catabolism of chylomicron remnants. Study 6 was an hypothesis-generating exercise examining the effects of 4-weeks pravastatin treatment on postprandial dyslipidaemia found in 7 postmenopausal women with type 2 DM from Study 5. Although plasma LDL-cholesterol was reduced (-19%, p=0.028), there were no significant effects found on fasting apoB48 concentrations (-12%, p=0.116) or the FCR of the chylomicron remnant-like emulsion (+38%, p=0.345). A larger sample size of patients and/or treatment with a more potent statin at a dosage known to affect chylomicron remnant metabolism would be required to demonstrate a significant reduction in postprandial dyslipidaemia in postmenopausal women with type 2 DM. The results of the above mentioned studies combined support the general hypothesis that postprandial dyslipidaemia is a feature of patients with or at risk of CAD. This defect may be demonstrated using fasting apoB48 as an indicator of the degree of postprandial lipaemia. Postprandial dyslipidaemia may reflect a reduction in catabolism, as suggested with the breath test in type 2 DM, and/or an over overproduction of chylomicrons. Both these mechanisms would also increase competition for lipolysis and clearance pathways between hepatically and intestinally-derived lipoproteins. The exact mechanisms by which postprandial dyslipidaemia occurs are yet to be determined. Statins appear to improve defective postprandial lipaemia in patients with or at risk of CAD, which is in agreement with the general hypothesis. The effectiveness of a statin is dependant on their potency in inhibiting cholesterol biosynthesis and increasing receptor mediated clearance of LDL and chylomicron remnants. The studies conducted in this thesis show that postprandial dyslipidaemia can be reduced by statins but not to the extent demonstrated in controls. However, the demonstrated reduction in fasting and total postprandial lipaemia translates to a lowering in overall arterial exposure to circulating proatherogenic particles. The elevation in fasting and postprandial levels of proatherogenic chylomicron remnants found in the patient groups described in this thesis indicates another dimension to their risk of coronary disease. The reductions in the overall levels of proatherogenic particles in patients with or at high CAD risk, infers a possible reduction in the risk of coronary disease in these patients.

O receptor sensor do cálcio (CASR) desempenha um importante papel na manutenção da concentração plasmática do cálcio. Desde a sua descrição, mais de 200 mutações foram descritas podendo levar à perda ou ao ganho de função, resultando em situações de hiper ou hipocalcemia, respectivamente. Mutações inativadoras estão associadas à hipercalcemia hipocalciúrica familiar (HHF) e ao hiperparatireoidismo neonatal grave (HPTNG), enquanto que mutações ativadoras estão associadas à hipocalcemia autossômica dominante (HAD) e à Síndrome de Bartter tipo V. O objetivo deste estudo foi realizar o diagnóstico molecular, por meio da análise do gene CASR, em pacientes com HPTNG, HHF, hipocalcemia com PTH inapropriadamente normal ou baixo e hipoparatireoidismo idiopático com hipercalciúria na vigência de tratamento. Para cada criança (n = 2) com diagnóstico clínico e laboratorial de HPTNG, uma mutação \"nonsense\" em homozigose foi identificada na região codificadora do CASR (p.E519X e p.R544X). O estudo molecular dos pais das crianças mostrou tratar-se de casos herdados caracterizando-os como indivíduos com HHF e possibilitou o aconselhamento genético para estas famílias. Mutações pontuais em heterozigose na região codificadora do CASR (p.R25X, p.R69H, p.T627I) foram detectadas em três dos quatro pacientes selecionados com diagnóstico inicial de hiperparatireoidismo primário e bioquímica compatível com hipercalcemia hipocalciúrica. Estes achados constituem a base molecular da HHF e permitiram o rastreamento de outros casos de HHF nas respectivas famílias com impacto na abordagem terapêutica dos mesmos. Na paciente em que não foi detectada nenhuma mutação na região codificadora do CASR, o estudo prosseguiu com a pesquisa de alterações no número de cópias gênicas e de mutações nas regiões promotoras P1 e P2 como possíveis causas do fenótipo em questão. O resultado destas abordagens foi normal. Dos quatro pacientes selecionados com quadro de hipoparatireoidismo idiopático e hipercalciúria na vigência de tratamento, em apenas uma, a causa molecular foi definida por mutação \"missense\" em heterozigose na região codificadora do CASR (p.E767K) repercutindo positivamente no seu tratamento. Nos demais casos (n = 3), a pesquisa de alterações no número de cópias gênicas e de mutações nas regiões promotoras P1 e P2 também resultou normal. / The calcium sensing receptor (CASR) plays an important role in maintaining the plasma concentration of calcium. From its first description, more than 200 mutations have been described leading to loss or gain of function, resulting in conditions of either hyper or hypocalcemia, respectively. Inactivating mutations are associated with familial hypocalciuric hypercalcemia (FHH) and neonatal severe hyperparathyroidism (NSHPT), whereas activating mutations are associated with autosomal dominant hypocalcemia (ADH) and type V Bartter\'s syndrome. The aim of this study was to perform the molecular diagnosis, by analyzing the CASR gene, in patients with NSHPT, FHH, hypocalcemia with inappropriately normal or low PTH and idiopathic hypoparathyroidism with hypercalciuria during treatment. In every child (n = 2) with clinical and laboratory diagnosis of NSHPT, a nonsense mutation in homozygosity was identified in the coding region of the CASR (p.E519X and p.R544X). The molecular analysis of the child\'s parents showed that they were inherited cases qualifying them as individuals with FHH and it enabled a genetic counseling for these families. Point mutations in heterozygosity in the coding region of the CASR (p.R25X, p.R69H, p.T627I) have been detected in three out of the four selected patients with an initial diagnosis of primary hyperparathyroidism and biochemistry compatible with hypocalciuric hipercalcemia. These findings are the molecular basis of FHH and allowed the screening of other FHH cases in these families impacting on their therapeutic approach. In patients where no mutation in the coding region of the CASR was detected, the study went on researching for changes in the number of gene copies and mutations in P1 and P2 promoter regions as possible causes to the phenotype in question. The result of these approaches has been normal. The molecular cause has been defined as missense mutation in heterozygosis in the coding region of the CASR (p.E767K) in only one out of the four selected patients with idiopathic hypoparathyroidism and hypercalciuria during treatment, with a positive impact on her treatment. In the other cases (n = 3), the search for changes in the number of gene copies and mutations in the P1 and P2 promoter regions was normal.

MPH / Department of Public Health / Obesity has been viewed as a serious problem that affects people of all ages, races, ethnicity, and political, religious, social and economic status. It presents a major health challenge worldwide, with an estimated 2 to 3 billion of overweight adults and 700 million of obese individuals. A cross- sectional descriptive research survey using quantitative approach was used to collect data from 318 adults aged 18-45 at Tshikota Location.. Data will be analysed using the Statistical Package for Social Sciences (SPSS) version 22.0. Cross tabulations and the Pearson’s Chi-square test will be used to obtain the associations and strength of relationship between independent and dependent variables. Results: Higher prevalence of obesity (35.5%) and overweight (28.6%) was found among the sampled population. The prevalence of obesity was found to be higher in males (51.3%) than females (46.7%), males also showed high prevalence in overweight (57.1%) than females (42.9%). There was significant different between socioeconomic status, family history and BMI. 75.2% of the participants who are obese was of those participants who do not engage in physical activity. Majority of the participants (63.5%) take meals 3 times a day and they are more likely to be obese, 19.2% of the participants do not skip breakfast. Mode of transport was positive significant to BMI as a sedentary behaviour. Neighbourhoods environment and psychological factors showed negative significant to BMI. Conclusion: The findings of this study found the prevalence of obesity and overweight to be high among residents of Tshikota Location. Males showed higher prevalence of obesity than females, they also showed high prevalence in overweight compared to that of females. Factors contributing to obesity were found to be diverse, they include socio- demographic, lifestyle, behavioral, environment, psychological and family history. / NRF

MPH / Department of Public Health / Sedentary lifestyle may contribute to obesity and non-communicable diseases, which are the major public health problem in South Africa. This study investigated the relationship between sedentary lifestyle and obesity among adults in Ha-Tshikundamalema area. A quantitative descriptive cross-sectional study among 298 participants (116 males and 182 females) aged 20-60 years, sampled systematically was conducted. Socio-demographic and, sedentary lifestyle and physical activity information was collected using a questionnaire, while anthropometric indices were measured according to ISAK protocol. Data were analysed using SPSS, version 24.0; where Pearson correlation and linear regression analyses to determine significant predictors of obesity were performed. The prevalence of TV viewing and low participation in moderate-vigorous activity were 75.8%, 69.1% and 82.6%, respectively. Twenty-nine point nine percent and 27.2% were overweight and obese, while 26.8% had very high WC (central obesity). According to Pearson correlation, TV viewing time, food, household activity, walking days and time, vigorous activity work vigorous activity, female gender, age (30-39), being married, unemployment, smoking and alcohol consumption were significantly related to BMI and WC. No significant association was found between most of the sedentary behaviours, level of education and socio-economic status. However, obesity was more prevalent among those with less education and low socio-economic status. In regression analyses, only TV viewing time, work vigorous activity, gender, being married and smoking were the independent and significant predictors of high BMI and WC (obesity) (P< 0.05). There was an association of sedentary lifestyle and socio-demographic characteristics, and obesity. Intervention to prevent sedentary lifestyle and obesity should target females, particularly married, unemployed and those with less level of education. / NRF

Indiana University-Purdue University Indianapolis (IUPUI) / Giant axonal neuropathy (GAN) is a rare genetic disease that causes progressive damage to the nervous system. Neurons in GAN patients develop an abnormal organization of cytoskeletal proteins called intermediate filaments (IFs), which normally provide strength and support for the overall cell structure. The irregular IF structure in GAN patient neurons leads to a progressive loss of motor skills in children and subsequent death in adolescence. GAN is caused by reduced levels of the gigaxonin (Giga) protein. Giga functions to control the degradation of other cellular proteins, and the loss of Giga in GAN cells results in significantly elevated levels of the galectin-1 (Gal-1) protein. Gal-1 stabilizes the active form of the Ras signaling protein, which functions as a molecular switch to regulate the phosphorylation and subsequent organization of IFs. The connection between these pathways led us to propose that Giga regulates IF phosphorylation and structure by modulating Ras signaling through the degradation of Gal-1. Using GAN patient cells, we demonstrated that restoring Giga reduced Gal-1 protein levels, decreased IF phosphorylation, and reestablished normal IF organization. Similar effects of reduced IF phosphorylation and improved IF structure were also obtained in GAN cells by directly decreasing the protein levels of either Gal-1, or downstream Ras signaling proteins. Taken together, these results demonstrate that the loss of Giga induces Gal-1 mediated activation of Ras signaling, thereby leading to the increased IF phosphorylation and abnormal IF structure observed in GAN cells. Identification of aberrant Ras signaling is significant because it is the first to specify a mechanism by which the loss of Giga leads to the development of GAN and provides targets for novel drug therapies for the treatment of this currently immedicable genetic disease.

Indiana University-Purdue University Indianapolis (IUPUI) / Non-alcoholic fatty liver disease and metabolic syndrome induced by high nutrient status have increasingly become a global health concern as it cause multiple complications. The mTOR complex is central in regulating anabolic reactions within cells under growth factors or under high nutrients stimulation. Constitutive and persistent activation of mTOR can impair cellular functions. In the first part of this study, we demonstrate a damping oscillation of mTOR activity during a long-term treatment of high fat diet. TFEB translocation and lysosomal enzyme activity also oscillate, but in an opposite direction. TFEB controls the lysosomal activity, autophagic degradation and lipid metabolism. Overexpression of wild type and mutant TFEB could inhibit NAFLD development in mice. In addition, TFEB location in nucleus inversely correlates with NAFLD severity in patients. mTOR activation under hypernutrition status suppresses TFEB translocation, inhibits lysosomal functions and autophagic degradation of lipid droplets. Inhibition of mTOR activity by rapamycin reverse the above phenotypes. Because mTOR activation also requires normal lysosomal function, the inhibition of TFEB by mTOR leads to decreased lysosomal function and mTOR downregulation. This negative feedback may explain the oscillation pattern of mTOR activation in long term high fat diet regimen and is a novel mechanism for inhibition of mTOR. In the second part of study, we report that Bid protein, previously known for its pro-apoptosis function in promoting mitochondrial permeability, plays an unexpected role in regulating fatty acid beta oxidation. Deletion of Bid in mice reprograms the body's response to hyper-nutrition caused by high fat diet, leading to the resistance to the development of obesity, liver steatosis and metabolic syndrome. These mice present a higher oxygen consumption, a lower respiratory quotient, and an increased beta-oxidation rate. Mechanistically, the high fat diet regimen triggers translocation of the full length Bid molecule to mitochondrial membrane. Genetic deletion of Bid also affects the stability of its binding protein, MTCH2 in the mitochondrial membrane. In summary, we describe in this study a mTOR-TFEB-lysosome feedback loop, which can regulate NAFLD development, and a novel Bid-mediated regulatory mechanism in beta-oxidation, which limits energy expenditure and promotes obesity development.

Indiana University-Purdue University Indianapolis (IUPUI) / Signal Transducer and Activator of Transcription 3 (STAT3) is known to be related to bone metabolism. Mutation of STAT3 causes a rare disorder in which serum levels of IgE are elevated. This causes various skeletal problems similar to osteoporosis. To examine the effect of STAT3 in the osteoclast, we obtained two osteoclast specific STAT3 knockout mouse models: one using the CTSK promoter to drive Cre recombinase and another using a TRAP promoter. Examination of these mice at 8 weeks of age revealed a decreased trabecular bone volume in CTSK specific STAT3 knockout mice along with a slight decrease in osteoclast number in both CTSK and TRAP specific STAT3 knockout females. We also noticed changes in bone mineral density and bone mechanical strength in females. These data suggest that STAT3 plays a part in the function of the osteoclast.

INTRODUÇÃO: O consumo mundial de açúcar triplicou nos últimos 50 anos e a sua ingesta abusiva é responsável pela resistência periférica à insulina, que origina a síndrome metabólica - obesidade, diabetes melito, hipertensão arterial e doenças coronarianas . Motivados pelo elevado número de pacientes que nos procuram com queixas vestibulares associadas aos distúrbios de metabolismo da glicose (DMG) resolvemos avaliar de forma objetiva, a influência dos DMG nas disfunções labirínticas e o efeito da dieta restritiva de carboidratos como forma de tratamento. OBJETIVO: Observar o impacto da dieta fracionada e restritiva de carboidratos na qualidade de vida dos pacientes portadores de distúrbios do equilíbrio corporal e DMG por meio da posturografia dinâmica computadorizada (PDC), do disability index (DI) e da escala análogo-visual (EAV). CASUÍSTICA E METODOLOGIA: Este estudo foi desenhado como um ensaio clínico prospectivo controlado randomizado realizado no Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. A amostra foi constituída de 51 pacientes divididos em dois grupos: Grupo Dieta (GD): indivíduos tratados com comprimidos de placebo e dieta fracionada com restrição de glicose, Grupo Controle (GC): receberam apenas placebo. Os pacientes realizaram PDC, DI e EAV no primeiro e trigésimo dias do estudo. RESULTADOS: A amostra mostrou-se homogêna quando comparados os grupos e observou-se melhora, estatísticamente comprovada nas condições posturográficas avaliadas quando comparados GD e GC. Observou-se ainda melhora clínica do GD na análise da EAV. CONCLUSÃO: A dieta fracionada e restritiva de carboidratos mostrou-se eficaz no tratamento da nossa amostra de pacientes portadores de disfunções vestibulares associadas a DMG. / INTRODUCTION: World sugar consumption has tripled in the last 50 years and its abusive ingestion is responsible for peripheral insulin resistance, which leads to metabolic syndrome - obesity, diabetes mellitus, hypertension and coronary heart disease. Because of the high number of patients with vestibular complaints and with glucose metabolism disorders (GMD) we decided to objectively evaluate the effect of glucose restrictive and fractionated diet as a option of treatment in these patients. OBJECTIVE: To evaluate the impact of the glucose restrictive and fractionated diet on the Computerized Dynamic Posturography (CDP), disability index (DI) and the visual analogue scale (VAS) in patients with balance disorders and disorders of glucose metabolism. SAMPLES AND METHODOLOGY: Randomized controlled trial. Sample of 51 patients divided into two groups: Diet Group (DG) treated with placebo pills and glucose restrictive and fractionated diet and Control Group (CG) with only placebo. The individuals performed CDP, DI and VAS at first and thirtieth days of study. RESULTS: The sample groups were homogeneous before the study. There were significant improvement of DG on CDP conditions 4, 5, 6 and composite score. There was, also, significant improvement of VAS analysis on DG after intervention. CONCLUSION: The glucose restrictive and fractionated diet was effective in the treatment of patients with vestibular dysfunction associated with glucose metabolism disorders