RESUMO
OBJECTIVE: To estimate the prevalence of diabetes, hypertension, obesity, and describe demographic, anthropometric and medical characteristics, in a genetically distinct population: the Brazilian Xavante Indians. DESIGN: Population-based survey carried out among 948 Xavante from Mato Grosso, Brazil. Fasting and 2-hour after 75 g glucose capillary glycemia were measured by a portable glucometer (HemoCue Glucose201+). Diabetes was defined according to WHO criteria. Anthropometric data and medical characteristics were measured, and fat mass (%) was evaluated using bioelectrical impedance. Blood pressure was measured by an automated device (OMRON 742INTC), and hypertension was defined according to WHO criteria. RESULTS: Age-adjusted prevalence rates with 95% confidence intervals were diabetes: 28.2% (25.3-31.1) in general, 18.4% (14.9-22.2) in men and 40.6% (36.2-45.1) in women (P<.001); impaired glucose tolerance: 32.3% (20.5-26.0) in general, 29.7% (25.4-33.9) in men and 34.4% (30.2-38.8) in women (P>.05); hypertension: 17.5% (15.1-19.9) in general. Obesity was found in 50.8% of the individuals. Fat mass (%) was associated with diabetes in men (P<.05) and women (P<.05). Thigh circumference and waist/ thigh ratio were lower in those with diabetes, in men and women (P<.001). CONCLUSIONS: The high prevalence of diabetes and obesity in Xavante is likely related to their recent change in food habits and physical activities. Our results should raise awareness about the magnitude of this health problem and also indicate that it could increase dramatically in the future if no preventive actions are adopted.
Assuntos
Diabetes Mellitus Tipo 2/etnologia , Indígenas Sul-Americanos/estatística & dados numéricos , Adulto , Antropometria , Brasil , Feminino , Intolerância à Glucose/etnologia , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/etnologia , PrevalênciaRESUMO
Lipodystrophies are characterized by complete or selective loss of adipose tissue and can be acquired or inherited. Familial partial lipodystrophy (FPLD) is a hereditary lipodystrophy commonly caused by mutations in the LMNA gene. Herein, we report two cases of FPLD associated with podocytopathies. Patient 1 was diagnosed with FPLD associated with the heterozygous p.Arg482Trp variant in LMNA and had normal glucose tolerance and hyperinsulinemia. During follow-up, she developed nephroticrange proteinuria. Renal biopsy was consistent with minimal change disease. Patient 2 was diagnosed with FPLD associated with a de novo heterozygous p.Arg349Trp variant in LMNA. Microalbuminuria progressed to macroalbuminuria within 6 years and tonephrotic range proteinuria in the last year. He remained without diabetes and with hyperinsulinemia. Renal biopsy revealed focal segmental glomerulosclerosis not otherwise specified. This report provides further evidence of variable features of lipodystrophy associated with LMNA variants and the importance of long-term follow-up with evaluation of kidney dysfunction.
Assuntos
Lamina Tipo A , Lipodistrofia Parcial Familiar , Humanos , Lamina Tipo A/genética , Lipodistrofia Parcial Familiar/genética , Lipodistrofia Parcial Familiar/complicações , Feminino , Masculino , Adulto , Podócitos/patologia , MutaçãoRESUMO
It has been suggested that the higher susceptibility of Hispanics to metabolic disease is related to their Native American heritage. A frequent cholesterol transporter ABCA1 (ATP-binding cassette transporter A1) gene variant (R230C, rs9282541) apparently exclusive to Native American individuals was associated with low high-density lipoprotein cholesterol (HDL-C) levels, obesity and type 2 diabetes in Mexican Mestizos. We performed a more extensive analysis of this variant in 4405 Native Americans and 863 individuals from other ethnic groups to investigate genetic evidence of positive selection, to assess its functional effect in vitro and to explore associations with HDL-C levels and other metabolic traits. The C230 allele was found in 29 of 36 Native American groups, but not in European, Asian or African individuals. C230 was observed on a single haplotype, and C230-bearing chromosomes showed longer relative haplotype extension compared with other haplotypes in the Americas. Additionally, single-nucleotide polymorphism data from the Human Genome Diversity Panel Native American populations were enriched in significant integrated haplotype score values in the region upstream of the ABCA1 gene. Cells expressing the C230 allele showed a 27% cholesterol efflux reduction (P< 0.001), confirming this variant has a functional effect in vitro. Moreover, the C230 allele was associated with lower HDL-C levels (P = 1.77 x 10(-11)) and with higher body mass index (P = 0.0001) in the combined analysis of Native American populations. This is the first report of a common functional variant exclusive to Native American and descent populations, which is a major determinant of HDL-C levels and may have contributed to the adaptive evolution of Native American populations.
Assuntos
Transportadores de Cassetes de Ligação de ATP/genética , HDL-Colesterol/sangue , Indígenas Norte-Americanos/genética , Seleção Genética , Transportador 1 de Cassete de Ligação de ATP , Transportadores de Cassetes de Ligação de ATP/fisiologia , Adulto , Alelos , HDL-Colesterol/genética , Feminino , Frequência do Gene , Genética Populacional , Estudo de Associação Genômica Ampla , Geografia , Haplótipos , Humanos , Desequilíbrio de Ligação , MasculinoRESUMO
BACKGROUND AND AIMS: Common variants in fat mass and obesity-associated (FTO) gene have been implicated as a susceptibility locus for obesity and type 2 diabetes in different populations. Here, in an indigenous population-based study, we examined whether FTO rs9939609 has a role in susceptibility to glucose intolerance and obesity. METHODS: The study population comprised 949 full Xavante indigenous people (465 men) aged 18-99 years. The participants were submitted to clinical examination, anthropometrical measures and basal and 2-h post 75g oral glucose load capillary glucose measurements. FTO rs9939609 was genotyped and logistic regression was carried out to test the additive effect of the risk allele. RESULTS: The frequency of the minor allele of the FTO rs9939609 (0.06) was lower in Xavante than observed in some populations. A significant association between the variant and overweight was observed (OR = 1.56 (95% CI:1.06-2.29, p = 0.02), using an additive model of inheritance, adjusted by age and gender and considering the family structure. We found no associations with obesity or glucose intolerance. CONCLUSIONS: The FTO rs9939609 is associated with overweight, but not with obesity or glucose intolerance. The low frequency of the A allele suggests that it is not an important risk determinant for these conditions in Xavante indigenous people.
Assuntos
Diabetes Mellitus Tipo 2 , Intolerância à Glucose , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética , Índice de Massa Corporal , Brasil , Diabetes Mellitus Tipo 2/complicações , Predisposição Genética para Doença , Genótipo , Intolerância à Glucose/complicações , Intolerância à Glucose/epidemiologia , Intolerância à Glucose/genética , Humanos , Povos Indígenas , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Polimorfismo de Nucleotídeo Único , Adulto JovemRESUMO
AIMS: Maturity-Onset Diabetes of the Young (MODY) caused by glucokinase (GCK) mutations is characterized by lifelong mild non-progressive hyperglycemia, with low frequency of coronary artery disease (CAD) compared to other types of diabetes. The aim of this study is to estimate cardiovascular risk by coronary artery calcification (CAC) score in this group. MATERIALS AND METHODS: Twenty-nine GCK-MODY cases, 26 normoglycemic controls (recruited among non-affected relatives/spouses of GCK mutation carriers), and 24 unrelated individuals with type 2 diabetes were studied. Patients underwent CAC score evaluation by computed tomography and were classified by Agatston score ≥ or < 10. Framingham Risk scores of CAD in 10 years were calculated. RESULTS: Median [interquartile range] CAC score in GCK-MODY was 0 [0,0], similar to controls (0 [0,0], P = 0.49), but lower than type 2 diabetes (39 [0, 126], P = 2.6 × 10-5). A CAC score ≥ 10 was seen in 6.9% of the GCK group, 7.7% of Controls (P = 1.0), and 54.2% of individuals with type 2 diabetes (P = 0.0006). Median Framingham risk score was lower in GCK than type 2 diabetes (3% vs. 13%, P = 4 × 10-6), but similar to controls (3% vs. 4%, P = 0.66). CONCLUSIONS: CAC score in GCK-MODY is similar to control individuals from the same family and/or household and is significantly lower than type 2 diabetes. Besides demonstrating low risk of CAD in GCK-MODY, these findings may contribute to understanding the specific effect of hyperglycemia in CAD.
Assuntos
Cálcio/sangue , Vasos Coronários/metabolismo , Diabetes Mellitus Tipo 2/diagnóstico , Fatores de Risco de Doenças Cardíacas , Adulto , Idoso , Cálcio/análise , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/etiologia , Estudos de Casos e Controles , Vasos Coronários/química , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/genética , Angiopatias Diabéticas/sangue , Angiopatias Diabéticas/diagnóstico , Feminino , Glucoquinase/genética , Humanos , Hiperglicemia/genética , Masculino , Pessoa de Meia-Idade , Mutação , Prognóstico , Medição de Risco , Fatores de RiscoRESUMO
BACKGROUND AND AIMS: Type 2 diabetes is a multifactorial disease resulting from diverse genetic and environmental factors as well as the interaction between them. Low levels of 25-hydroxyvitamin D [25(OH)D], an indicator of vitamin D status, have been associated with an increased risk of type 2 diabetes, but not consistently. Also, it remains to be determined if this association differs among ethnic groups. Therefore, we aimed to evaluate vitamin D status and its association with glucose intolerance in a Brazilian indigenous population, the Xavante Indians. METHODS: The study population consisted of 819 full Xavante Indians (410 women), aged ≥18 years and living in two indigenous reserves located in Mato Grosso State, central region of Brazil. Clinical examination and anthropometrical measurements were made, blood samples were obtained for total cholesterol, HDL-cholesterol, triglycerides and 25(OH)D measurement. Fasting and 2-h post 75 g oral glucose load capillary glucose was measured. Vitamin D status was defined by serum 25(OH)D levels: vitamin D sufficiency (25(OH)D: 30-100 ng/mL), vitamin D insufficiency (25(OH)D: 20- <30 ng/mL) and vitamin D deficiency (25(OH)D: < 20 ng/mL). Multiple logistic regression was performed to identify independent associations between 25(OH)D levels and impaired glucose tolerance or diabetes mellitus. RESULTS: Analyses stratified by 25(OH)D levels shows that 65.5% of the population had vitamin D deficiency/insufficiency (25(OH)D < 30 ng/mL). 25(OH)D concentrations were lower in individuals with impaired glucose tolerance or diabetes mellitus than in normal glucose tolerant individuals. Multiple logistic regression analysis showed an inverse association between increments of 25(OH)D and presence of diabetes mellitus (OR per 1 ng/mL increase in 25(OH)D: 0.97; 95% confidence interval: 0.95-0.99), or impaired glucose tolerance (OR per 1 ng/mL increase in 25(OH)D: 0.87; 95% confidence interval: 0.85-0.89), in an age, sex, BMI and season of sampling-adjusted model. CONCLUSIONS: The present population-based study found a high prevalence of hypovitaminosis D among Xavante Indians. In this at-risk population of type 2 diabetes, a significant association of higher serum 25(OH)D with a decreased prevalence of diabetes mellitus and impaired glucose tolerance was observed.
Assuntos
Intolerância à Glucose/epidemiologia , Grupos Populacionais/estatística & dados numéricos , Deficiência de Vitamina D/epidemiologia , Vitamina D/análogos & derivados , Adulto , Idoso , Índice de Massa Corporal , Brasil/epidemiologia , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Intolerância à Glucose/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Fatores Sexuais , Vitamina D/sangue , Circunferência da CinturaRESUMO
Congenital hyperinsulinism of infancy (CHI) is the most common cause of hypoglycemia in newborns and infants. Several molecular mechanisms are involved in the development of CHI, but the most common genetic defects are inactivating mutations of the ABCC8 or KCNJ11 genes. The classical treatment for CHI has been pancreatectomy that eventually leads to diabetes. More recently, conservative treatment has been attempted in some cases, with encouraging results. Whether or not the patients with heterozygous ABCC8 mutations submitted to conservative treatment may spontaneously develop type 2 diabetes in the long run, is a controversial issue. Here, we report a family carrying the dominant heterozygous germ line E1506K mutation in ABCC8 associated with persistent hypoglycemia in the newborn period and diabetes in adulthood. The mutation occurred as a de novo germ line mutation in the mother of the index patient. Her hypoglycemic symptoms as a child occurred after the fourth year of life and were very mild, but she developed glucose metabolism impairment in adulthood. On the other hand, in her daughter, the clinical manifestations of the disease occurred in the neonatal period and were more severe, leading to episodes of tonic-clonic seizures that were well controlled with octreotide or diazoxide. Our data corroborate the hypothesis that the dominant E1506K ABCC8 mutation, responsible for CHI, predisposes to the development of glucose intolerance and diabetes later in life.
Assuntos
Transportadores de Cassetes de Ligação de ATP/genética , Hiperinsulinismo Congênito/complicações , Diabetes Mellitus/genética , Diabetes Gestacional/genética , Epilepsia Tônico-Clônica/etiologia , Canais de Potássio Corretores do Fluxo de Internalização/genética , Receptores de Droga/genética , Adulto , Criança , Hiperinsulinismo Congênito/genética , Diazóxido/uso terapêutico , Epilepsia Tônico-Clônica/tratamento farmacológico , Epilepsia Tônico-Clônica/genética , Feminino , Humanos , Hipoglicemia/complicações , Hipoglicemia/genética , Recém-Nascido , Octreotida/uso terapêutico , Gravidez , Receptores de SulfonilureiasRESUMO
OBJECTIVE: Adiponectin is an important mediator of insulin sensitivity, encoded by the ADIPOQ gene. Here we describe two Japanese-Brazilian families with hypoadiponectinaemia due to a novel mutation in ADIPOQ. DESIGN AND PATIENTS: In this study, we examined the entire translated regions of adiponectin in Japanese-Brazilians, a population with one of the highest prevalence rates of diabetes worldwide. We screened 200 patients with type 2 diabetes (DM) and 240 age-matched subjects with normal glucose tolerance. RESULTS: A novel heterozygous T deletion at position 186 in exon 2 of ADIPOQ, causing a frameshift at codon 62 and leading to a premature termination at codon 168 (p.Gly63ValfsX106), was found in two individuals with diabetes. This mutation was not found in 240 nondiabetic control subjects. In addition, we screened the mutation in an expanded set of 100 nondiabetic subjects from the general Brazilian population, but we found no mutations. In addition, six family members of the probands were identified as mutation-carriers. Individuals who were mutation-carriers had markedly low plasma adiponectin concentrations compared with those without the mutation [DM: 0.65 (0.59-1.34) microg/ml vs. 5.30 (3.10-8.55) microg/ml, P < 0.0001; normal glucose tolerance: 0.95 (0.76-1.48) microg/ml vs. 8.50 (5.52-14.55) microg/ml, P = 0.003]. All individuals carrying the p.Gly63ValfsX106 mutation and older than 30 years were found to be diabetic. CONCLUSIONS: We describe for the first time a frameshift mutation in exon 2 of the ADIPOQ gene, which modulates adiponectin levels and may contribute to the genetic risk of late-onset diabetes in Japanese-Brazilians.
Assuntos
Adiponectina/genética , Adiponectina/metabolismo , Diabetes Mellitus Tipo 2/etnologia , Diabetes Mellitus Tipo 2/genética , Mutação da Fase de Leitura , Adiponectina/química , Adulto , Sequência de Aminoácidos , Povo Asiático/genética , Sequência de Bases , Brasil/epidemiologia , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , LinhagemRESUMO
SUMMARY Lipodystrophies are characterized by complete or selective loss of adipose tissue and can be acquired or inherited. Familial partial lipodystrophy (FPLD) is a hereditary lipodystrophy commonly caused by mutations in the LMNA gene. Herein, we report two cases of FPLD associated with podocytopathies. Patient 1 was diagnosed with FPLD associated with the heterozygous p.Arg482Trp variant in LMNA and had normal glucose tolerance and hyperinsulinemia. During follow-up, she developed nephrotic-range proteinuria. Renal biopsy was consistent with minimal change disease. Patient 2 was diagnosed with FPLD associated with a de novo heterozygous p.Arg349Trp variant in LMNA. Microalbuminuria progressed to macroalbuminuria within 6 years and to nephrotic range proteinuria in the last year. He remained without diabetes and with hyperinsulinemia. Renal biopsy revealed focal segmental glomerulosclerosis not otherwise specified. This report provides further evidence of variable features of lipodystrophy associated with LMNA variants and the importance of long-term follow-up with evaluation of kidney dysfunction.
RESUMO
UNLABELLED: Maternal inherited diabetes and deafness (MIDD) has been related to an A to G transition in the mitochondrial RNA Leu (UUR) at base pair 3243. The prevalence of MIDD in the diabetes population ranges between 0.5-3.0% depending on the ethnic background. AIM: To examine the frequency and clinical features of diabetes associated with this mutation in Brazilian patients with glucose intolerance. METHODS: The study population comprised: 78 type 1 diabetic subjects (group I), 148 patients with type 2 diabetes (group II), 15 patients with either type 1 or type 2 diabetes and hearing loss (group III) and 492 Japanese Brazilians with varying degrees of glucose intolerance. DNA was extracted from peripheral blood leucocytes and the A3243G mutation was determined by PCR amplification and Apa 1 digestion. In some individuals DNA was also extracted from buccal mucosa and hair follicles. The 3243 bp mutation was found in three individuals, all from group III, resulting in a prevalence of 0.4%. These subjects had an early age of diagnosis of diabetes, low or normal body mass index and requirement of insulin therapy. In conclusion MIDD is rare in our population and should be investigate in patients with diabetes and deafness.
Assuntos
DNA Mitocondrial/genética , Surdez/genética , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 2/genética , Doenças Mitocondriais/genética , Mutação/genética , Adulto , Brasil/epidemiologia , Metabolismo dos Carboidratos/genética , Surdez/diagnóstico , Feminino , Frequência do Gene , Humanos , Transmissão Vertical de Doenças Infecciosas , Japão/etnologia , Masculino , Pessoa de Meia-Idade , Doenças Mitocondriais/diagnóstico , Linhagem , Reação em Cadeia da PolimeraseRESUMO
Neonatal diabetes, defined as the onset of diabetes within the first six months of life, is very rarely caused by pancreatic agenesis. Homozygous truncating mutations in the PTF1A gene, which encodes a transcriptional factor, have been reported in patients with pancreatic and cerebellar agenesis, whilst mutations located in a distal pancreatic-specific enhancer cause isolated pancreatic agenesis. We report an infant, born to healthy non-consanguineous parents, with neonatal diabetes due to pancreatic agenesis. Initial genetic investigation included sequencing of KCNJ11, ABCC8 and INS genes, but no mutations were found. Following this, 22 neonatal diabetes associated genes were analyzed by a next generation sequencing assay. We found compound heterozygous mutations in the PTF1A gene: A frameshift mutation in exon 1 (c.437_462 del, p.Ala146Glyfs*116) and a mutation affecting a highly conserved nucleotide within the distal pancreatic enhancer (g.23508442A>G). Both mutations were confirmed by Sanger sequencing. Isolated pancreatic agenesis resulting from compound heterozygosity for truncating and enhancer mutations in the PTF1A gene has not been previously reported. This report broadens the spectrum of mutations causing pancreatic agenesis.
Assuntos
Hiperglicemia/genética , Pâncreas/anormalidades , Fatores de Transcrição/genética , Humanos , Lactente , Recém-Nascido , Doenças do Recém-Nascido , Masculino , MutaçãoRESUMO
AIMS: Maturity-Onset Diabetes of the Young (MODY) comprises a heterogeneous group of monogenic forms of diabetes caused by mutations in at least 14 genes, but mostly by mutations in Glucokinase (GCK) and hepatocyte nuclear factor-1 homeobox A (HNF1A). This study aims to establish a national registry of MODY cases in Brazilian patients, assessing published and unpublished data. METHODS: 311 patients with clinical characteristics of MODY were analyzed, with unpublished data on 298 individuals described in 12 previous publications and 13 newly described cases in this report. RESULTS: 72 individuals had GCK mutations, 9 described in Brazilian individuals for the first time. One previously unpublished novel GCK mutation, Gly178Ala, was found in one family. 31 individuals had HNF1A mutations, 2 described for the first time in Brazilian individuals. Comparisons of GCK probands vs HNF1A: age 16±11 vs 35±20years; age at diagnosis 11±8 vs 21±7years; BMI 19±6 vs 25±6kg/m2; sulfonylurea users 5 vs 83%; insulin users 5 vs 17%; presence of arterial hypertension 0 vs. 33%, all p<0.05. No differences were observed in lipids and C-peptide. CONCLUSIONS: Most MODY cases in Brazil are due to GCK mutations. In agreement with other studied populations, novel mutations are common. Only 14% of patients with familial diabetes carry a HNF1A mutation. Diagnosis of other rare forms of MODY is still a challenge in Brazilian population, as well as adequate strategies to screen individuals for molecular diagnosis.
Assuntos
Diabetes Mellitus Tipo 2/genética , Fator 1-alfa Nuclear de Hepatócito/genética , Adolescente , Adulto , Brasil , Diabetes Mellitus Tipo 2/diagnóstico , Feminino , Humanos , Masculino , Sistema de Registros , Adulto JovemRESUMO
Maternally-inherited diabetes and deafness (MIDD) has been related to an A to G transition in the mitochondrial tRNA Leu (UUR) gene at the base pair 3243. Although some previous articles have reported that this mutation may be a cause of cardiomyopathy in diabetes, the degree of cardiac involvement and a specific treatment has not been established. Here, we reported a case of a patient with MIDD who developed congestive heart failure and the therapeutic usefulness of Coenzyme Q10 (CoQ10). In our patient, after the introduction of Coenzyme Q10 150 mg/day, there was a gradual improvement on left ventricular function evaluated by echocardiography. The fractional shortening (FS) and ejection fraction (EF) increased from 26 to 34% and from 49 to 64%, respectively. No side effects were noted. Three months after CoQ10 discontinuation, the parameters of systolic function evaluated by echocardiography decreased, suggesting that CoQ10 had a beneficial effect. Identification of diabetes and cardiomyopathy due to mitochondrial gene mutation may have therapeutic implications and Coenzyme Q10 is a possible adjunctive treatment in such patients.
Assuntos
Cetoacidose Diabética/tratamento farmacológico , Coração/fisiopatologia , Ubiquinona/análogos & derivados , Adulto , Antioxidantes/uso terapêutico , Coenzimas , DNA Mitocondrial/genética , Cetoacidose Diabética/complicações , Feminino , Testes de Função Cardíaca , Humanos , Insulina/uso terapêutico , Mutação de Sentido Incorreto , RNA de Transferência de Leucina/genética , Ubiquinona/uso terapêutico , Síndrome de Wolff-Parkinson-White/complicaçõesRESUMO
The objective of this study was to investigate whether decreased baseline adiponectin levels are an independent risk factor for development of glucose intolerance in a population-based study of Japanese-Brazilians, a group with one of the highest prevalence rates of diabetes worldwide. We examined 210 Japanese-Brazilians (97 male and 113 female, aged 56.7+/-10.1 years) with normal glucose tolerance (NGT). Plasma adiponectin, insulin, fasting and 2-h plasma glucose and lipid profile were evaluated at baseline and also at 7-year follow-up. Plasma adiponectin levels were significantly lower in glucose intolerance progressors compared with subjects who remained NGT. By increasing tertiles of adiponectin, the frequencies of subjects who progressed to glucose intolerance were 40%, 33% and 27% and the frequencies of subjects who remained NGT were 13%, 35% and 52% (chi2=15.8, p=0.001). Logistic regression analyses showed that adiponectin levels (OR for the highest versus lowest tertile: 0.31; 95% CI: 0.12-0.84, p=0.021), male sex (OR: 2.61, 95% CI: 1.21-5.65, p=0.015), fasting plasma glucose (0R: 3.05, 95% CI: 1.35-6.91, p=0.008) and waist circumference (OR: 1.04, 95% CI: 1.00-1.08, p=0.046) were independent risk factors for the progression to glucose intolerance. In conclusion, low plasma levels of adiponectin is one of several independent predictors of glucose intolerance in a Japanese-Brazilian population.
Assuntos
Adiponectina/sangue , Intolerância à Glucose/sangue , Adulto , Idoso , Glicemia/análise , Índice de Massa Corporal , Brasil/epidemiologia , Feminino , Seguimentos , Intolerância à Glucose/epidemiologia , Humanos , Japão/etnologia , Lipídeos/sangue , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
Wolfram syndrome (WS) is an autosomal recessive progressive neurodegenerative disorder characterized by diabetes mellitus and optic atrophy. Diabetes insipidus and sensorineural deafness are also noted frequently, explaining the acronym DIDMOAD (diabetes insipidus, diabetes mellitus, optic atrophy and deafness) by which the syndrome is also referred. Additional manifestations such as atonic bladder, ataxia, nystagmus and predisposition for psychiatric illness may be present. The Wolfram syndrome gene, WFS1, was mapped to chromosome 4p16.1 by positional cloning. It encodes an 890-amino-acid polypeptide named wolframin. Although the wolframin function is still not completely known, its localization to the endoplasmic reticulum suggests it can play a role in calcium homeostasis, membrane trafficking and protein processing. Knowing the cellular function of wolframin is necessary for understanding the pathophysiology of Wolfram syndrome. This knowledge may lead to development of therapies to prevent or reduce the outcomes of WS.
Assuntos
Proteínas de Membrana/fisiologia , Síndrome de Wolfram , Humanos , Proteínas de Membrana/genética , Mutação , Fatores de Tempo , Síndrome de Wolfram/genética , Síndrome de Wolfram/patologia , Síndrome de Wolfram/fisiopatologiaRESUMO
[This corrects the article DOI: 10.1186/1758-5996-4-40.].
RESUMO
Captopril, an angiotensin-converting enzyme (ACE) inhibitor, has been reported to improve insulin sensitivity. However, despite extensive investigation, the mechanisms responsible for this effect are not fully understood. Reduction of plasma angiotensin II and inhibition of kininase II have been suggested to contribute to improve insulin sensitivity. Insulin binding was measured at tracer insulin concentration in intact cells with or without captopril treatment. Specific binding, expressed as percent of total insulin added, was not different in control and captopril-treated cells. However, captopril treatment caused an increase in insulin-induced insulin receptor substrate-1 (IRS-1) phosphorylation accompanied by an increased association of IRS-1 with phosphoinositide-3 kinase (PI-3 kinase), despite no change on insulin receptor (IR) autophosphorylation. There was also an increased threonine kinase B (AKT) phosphorylation in captopril-treated cells followed by enhanced basal and insulin-stimulated glucose uptake. These results indicate that captopril treatment has a direct effect on early phosphorylation events induced by insulin in BC3H-1 myocytes.
Assuntos
Captopril/farmacologia , Insulina/farmacologia , Músculos/efeitos dos fármacos , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Animais , Transporte Biológico/efeitos dos fármacos , Linhagem Celular , Desoxiglucose/metabolismo , Glucose/metabolismo , Insulina/metabolismo , Proteínas Substratos do Receptor de Insulina , Peptídeos e Proteínas de Sinalização Intracelular , Camundongos , Camundongos Endogâmicos C3H , Músculos/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Fosfoproteínas/metabolismo , Fosforilação , Fosfotirosina/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Proto-Oncogênicas c-akt , Receptor de Insulina/metabolismoRESUMO
INTRODUCTION: A missense mutation in the glucagon receptor gene (Gly40Ser) has been associated with type 2 diabetes mellitus in some populations. AIM: To investigate whether this mutation is associated with type 2 diabetes in Brazilian patients and its functional significance in vivo. METHODOLOGY: One hundred fifteen patients with type 2 diabetes and 115 control subjects were screened by restriction-enzyme digestion with BstE II. The in vivo implications were investigated by 1 mg glucagon intravenous injection and plasma C-peptide (before and after 6 minutes) and glucose measurements (before and after 30, 60, 90, and 120 minutes), and first-phase insulin response (1 + 3 minutes) to intravenous glucose tolerance test. These procedures were performed in two groups of patients with diabetes, which differed only by the presence or absence of the Gly40Ser mutation, and two groups of control subjects. RESULTS: The mutation was detected in two patients with diabetes (1.7%) and in four control subjects (3.5%) (not significant). Patients with diabetes and carriers of Gly40Ser showed basal C-peptide levels significantly lower than noncarriers (0.70 ng/mL versus 1.50 ng/mL, p = 0.008). No differences were found between Gly40Ser carriers and noncarriers in control subjects within the parameters studied. CONCLUSION: Our results show that the Gly40Ser mutation in the glucagon receptor gene is not associated with type 2 diabetes in a Brazilian population. However, a reduction of insulin secretion was observed in Gly40Ser carriers.
Assuntos
Diabetes Mellitus Tipo 2/genética , Mutação de Sentido Incorreto , Receptores de Glucagon/genética , Adulto , Idoso , Brasil , Diabetes Mellitus Tipo 2/diagnóstico , Feminino , Fármacos Gastrointestinais/sangue , Testes Genéticos , Glucagon/sangue , Teste de Tolerância a Glucose , Heterozigoto , Humanos , Insulina/metabolismo , Secreção de Insulina , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND & AIMS: The aim of this study was to evaluate the usefulness of Body Adiposity Index (BAI) as a predictor of body fat in Xavante Indians and to investigate which anthropometric measures of adiposity best correlate with body fat in this population. METHODS: We evaluated 974 individuals (476 male), aged 42.3 ± 19.5 years. Percentage of body fat (%BF) determined by bioimpedance analysis (BIA) was used as the reference measure of adiposity. Bland-Altman analysis was used to assess the agreement between the two methods: BAI and BIA. Associations between anthropometric measures of adiposity were investigated by Pearson correlation analysis. RESULTS: BAI overestimates %BF (mean difference: 4.10%), mainly at lower levels of adiposity. Significant correlations were found between %BF and all measurements, being the strongest correlation with BAI. However, stratified analyses according to gender showed that among men waist circumference has the strongest correlation (r = 0.73, p < 0.001) and among women BAI (r = 0.71, p < 0.001), BMI (r = 0.69, p < 0.001) and waist circumference (r = 0.70, p < 0.001) performed similarly. CONCLUSION: BAI can be a useful tool to predict %BF in Xavante Indians, although it has some limitations. However, it is not a better predictor of adiposity than waist circumference in men or BMI and waist circumference in women.
Assuntos
Tecido Adiposo/metabolismo , Adiposidade , Indígena Americano ou Nativo do Alasca , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Peso Corporal , Estudos Transversais , Impedância Elétrica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Circunferência da Cintura , Adulto JovemRESUMO
BACKGROUND: Adiponectin circulates in different multimer complexes comprised of low molecular weight trimeric form (LMW), hexamer of middle molecular weight (MMW) and high molecular weight multimers (HMW). In Japanese-Brazilians, a population with high prevalence of glucose metabolism disturbances, we examined the associations of total adiponectin and its multimers with diabetes mellitus. METHODS: Two study groups were examined: 26 patients with diabetes mellitus (DM,14 women and 12 men, aged 55.3 ± 8.6 years) and 27 age-matched control subjects with normal glucose tolerance (NGT,12 women and 15 men, aged 54.0 ± 9.2 years). RESULTS: We found no significant differences in total [NGT: 6.90 ug/ml (4.38-13.43); DM: 5.38 ug/ml (3.76-8.56), p = 0.35], MMW [NGT:2.34 ug/ml (1.38-3.25); DM: 1.80 ug/ml (1.18-2.84), p = 0.48] or LMW adiponectin [NGT: 2.07 ug/ml (1.45-3.48), DM: 2.93 ug/ml (1.78-3.99), p = 0.32] between groups. In contrast, HMW adiponectin levels were significantly lower in patients with DM [TGN: 2.39 ug/ml (1.20-4.75); DM: 1.04 ug/ml (0.42-1.60), p = 0.001]. A logistic regression analysis was done to identify independent associations with diabetes mellitus. The results showed that HOMA-IR and HMW adiponectin in women were independently associated with diabetes mellitus. CONCLUSION: The current investigation demonstrates that in Japanese-Brazilians HMW adiponectin is selectively reduced in individuals with type 2 diabetes, while no differences were found in MMW and LMW adiponectin isoforms.