RESUMO
Obesity is associated with environmental factors; however, information about gene-environment interactions is lacking. We aimed to elucidate the effects of gene-environment interactions on obesity, specifically between genetic predisposition and various obesity-related lifestyle factors, using data from a population-based prospective cohort study. The genetic risk score (GRS) calculated from East Asian ancestry single-nucleotide polymorphisms was significantly associated with the body mass index (BMI) at baseline (P<0.001). Significant gene-environment interactions were observed for six nutritional factors, alcohol intake, metabolic equivalents-hour per day and the homeostasis model assessment ratio. The GRS altered the effects of lifestyle factors on BMI. Increases in the BMI at baseline per unit intake for each nutritional factor differed depending on the GRS. However, we did not observe significant correlations between the GRS and annual changes in BMI during the follow-up period. This study suggests that the effects of lifestyle factors on obesity differ depending on the genetic risk factors. The approach used to evaluate gene-environment interaction in this study may be applicable to the practice of preventive medicine.
Assuntos
Interação Gene-Ambiente , Predisposição Genética para Doença , Obesidade/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Genótipo , Humanos , Pessoa de Meia-Idade , Obesidade/patologia , Polimorfismo de Nucleotídeo Único , Fatores de RiscoRESUMO
Bilateral adrenal infarction is an extremely rare disease, and it has been reported that some coagulation abnormalities, including essential thrombocythemia (ET), exist in the background. We herein report a 76-year-old patient in whom the platelet count had been in the normal range at the onset of adrenal infarction but subsequently increased to 102×104/µL at 7 months later, leading to the diagnosis of JAK2V617F-positive ET. As the presence of the JAK2V617F mutation increases the risk of thrombosis, Janus kinase 2 (JAK2) genetic testing should be considered in some cases of nonspecific unknown thrombosis, even if there are no obvious hematological findings, such as clonal hematopoiesis of indeterminate potential (CHIP).
Assuntos
Doenças das Glândulas Suprarrenais , Trombocitemia Essencial , Trombose , Humanos , Idoso , Trombocitemia Essencial/complicações , Trombocitemia Essencial/diagnóstico , Trombocitemia Essencial/genética , Trombose/genética , Contagem de Plaquetas , Mutação , Infarto/diagnóstico por imagem , Infarto/etiologia , Janus Quinase 2/genéticaRESUMO
Aims: We aimed to verify the usefulness of targeted next-generation sequencing (NGS) technology for diagnosing monogenic diabetes in a single center. Methods: We designed an amplicon-based NGS panel targeting 34 genes associated with known monogenic diabetes and performed resequencing in 56 patients with autoantibody-negative diabetes mellitus diagnosed at < 50 years who had not been highly obese. By bioinformatic analysis, we filtered significant variants based on allele frequency (< 0.005 in East Asians) and functional prediction. We estimated the pathogenicity of each variant upon considering the family history. Results: Overall, 16 candidate causative variants were identified in 16 patients. Among them, two previously known heterozygous nonsynonymous single-nucleotide variants associated with monogenic diabetes were confirmed as causative variants: one each in the GCK and WFS1 genes. The former was found in two independent diabetes-affected families. Two novel putatively deleterious heterozygous variants were also assumed to be causative from the family history: one frameshift and one nonsynonymous single-nucleotide variant in the HNF4A gene. Twelve variants remained as candidates associated with the development of diabetes. Conclusion: Targeted NGS panel testing was useful to diagnose various forms of monogenic diabetes in combination with familial analysis, but additional ingenuity would be needed for practice. Supplementary Information: The online version contains supplementary material available at 10.1007/s13340-023-00669-3.
RESUMO
In several countries including Japan, people without obesity but with a clustering of metabolic risk factors (MetRFs) were not considered to have the metabolic syndrome (MetS). Here, we examined whether lifestyle characteristics differed between non-obese and obese subjects with or without a clustering of MetRFs. From a population-based cross-sectional study of Japanese subjects aged ≥ 40 years, 1,601 subjects (age: 61.9 ± 10.3 years; 710/891 men/women) were recruited. Physical activity status and daily nutritional intake were estimated using questionnaires. A clustering of MetRFs was defined based on the presence of at least two non-essential risk factors for the diagnosis of the MetS in Japan. Energy intake was not higher in subjects with a clustering of MetRFs compared with those without. Among men, energy expenditure at work was significantly lower in non-obese (9.0 ± 8.2 vs. 11.3 ± 9.3 metabolic equivalents (METs), P = 0.025) and obese (9.0 ± 7.9 vs. 11.6 ± 9.4 METs, P = 0.017) subjects with a clustering of MetRFs than in those without. Multiple logistic regression analysis showed that energy expenditure at work was significantly associated with a clustering of MetRFs after adjusting for possible confounding factors including total energy intake. The ORs (per 1 METs) were 0.970 (95% CI, 0.944-0.997; P = 0.032) in non-obese men and 0.962 (0.926- 0.999; P = 0.043) in obese men. Similar associations were not observed in women. In Japanese males, lower physical activity, but not excessive energy intake, is a risk factor for a clustering of MetRFs independent of their obesity status.
Assuntos
Metabolismo Energético , Síndrome Metabólica/epidemiologia , Atividade Motora , Obesidade/fisiopatologia , Sobrepeso/fisiopatologia , Comportamento Sedentário , Adulto , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Estudos de Coortes , Estudos Transversais , Ingestão de Energia , Feminino , Humanos , Japão/epidemiologia , Masculino , Síndrome Metabólica/etnologia , Síndrome Metabólica/etiologia , Síndrome Metabólica/metabolismo , Pessoa de Meia-Idade , Fatores de Risco , Comportamento Sedentário/etnologia , Fatores SexuaisRESUMO
OBJECTIVE: Targeted drugs are generally associated with a lower toxicity than conventional systemic cytotoxic drugs and, thus, are administered for long periods. As a result, unusual adverse effects, including thyroid dysfunction, have become important clinical issues. METHODS: We retrospectively collected the data and compared the incidence and the time of onset of thyroid dysfunction in 33 patients (M/F: 26/7, age: 34-77) with metastatic renal cell carcinoma treated with the small-molecule tyrosine kinase inhibitors (TKIs) sunitinib, sorafenib and axitinib in Yamagata University Hospital, Japan, from 2005 to 2010. RESULTS: The incidence of thyroid dysfunction tended to be higher in patients treated with axitinib (6 of 6: 100%) than in those treated with sunitinib (9 of 15: 60%) or sorafenib (6 of 12: 50%) (P= 0.1113). The median thyroid dysfunction-free survival evaluated using the Kaplan-Meier product-limit method with the log-rank test was significantly shorter in patients treated with axitinib than in those treated with sunitinib/sorafenib (3 vs. 16 weeks, P=0.0198). A multivariate Cox regression model for thyroid dysfunction-free survival with several probable confounding factors as co-variables showed that patients treated with axitinib were more likely to have thyroid dysfunction than the others (hazard ratio: 4.53, 95% confidence interval: 1.40-14.63, P=0.0116). CONCLUSIONS: Patients treated with the tyrosine kinase inhibitors developed thyroid dysfunction frequently. Furthermore, those treated with axitinib developed thyroid dysfunction significantly more and at a faster rate than the others. Therefore, when the tyrosine kinase inhibitors, especially axitinib, are used, close monitoring of thyroid function is recommended, at least for the initial 1-2 months, to avoid clinical symptoms derived from thyroid dysfunction.
Assuntos
Benzenossulfonatos/efeitos adversos , Carcinoma de Células Renais/tratamento farmacológico , Imidazóis/efeitos adversos , Indazóis/efeitos adversos , Indóis/efeitos adversos , Neoplasias Renais/tratamento farmacológico , Inibidores de Proteínas Quinases/efeitos adversos , Piridinas/efeitos adversos , Pirróis/efeitos adversos , Doenças da Glândula Tireoide/induzido quimicamente , Adulto , Idoso , Antineoplásicos/efeitos adversos , Axitinibe , Carcinoma de Células Renais/patologia , Feminino , Humanos , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Niacinamida/análogos & derivados , Compostos de Fenilureia , Proteínas Tirosina Quinases/antagonistas & inibidores , Sorafenibe , Sunitinibe , Doenças da Glândula Tireoide/epidemiologia , Doenças da Glândula Tireoide/mortalidade , Glândula Tireoide/efeitos dos fármacos , Glândula Tireoide/fisiopatologia , Tireotoxicose/induzido quimicamenteRESUMO
The association of the FTO gene polymorphism, rs9939609, with obesity was examined using the population of the Takahata study (n (M/F): 2,639 (1,168 / 1,470); age: 63.0 +/- 10.2 years), a Japanese community-based study. The effects of lifestyle-related factors, including nutritional intake and physical activities, on the association were also examined. Body mass index (BMI) was significantly associated with the FTO gene polymorphism (p<0.001). A case-control association study of the FTO gene polymorphism with obesity using multiple logistic regression analysis showed a significant association of the genotype AA (odds ratio, 1.53 [95% confidential interval, 1.04-2.24]) after adjustment for age and gender. Analysis to examine the differences in lifestyle-related factors among the genotype groups showed a significant difference in the energy expenditure for moderate to high-intensity physical activity (PA) (> or = 3.0 METs) (p=0.012) with a significant decrease toward the genotype AA (p=0.027). The effect of energy expenditure for moderate to high-intensity PA on the association of the polymorphism with obesity was then examined using study groups stratified based on the energy expenditure for moderate to high-intensity PA (Low-PA and High-PA). The BMI was significantly higher in the genotype AA in the Low-PA group (p=0.016) but not in the High-PA group (p=0.103). Furthermore, the genotype AA was significantly associated with obesity (odds ratio, 2.39 [95% confidential interval, 1.19-4.80]) in the Low-PA group but not in the High- PA group (p=0.650). The FTO gene, rs9939609, was associated with obesity, and the association was evident in subjects with low-PA, suggesting a PA-dependent association.
Assuntos
Obesidade/genética , Polimorfismo Genético/genética , Proteínas/genética , Idoso , Dioxigenase FTO Dependente de alfa-Cetoglutarato , Índice de Massa Corporal , Estudos de Casos e Controles , Estudos Transversais , Dieta , Ingestão de Energia , Metabolismo Energético/genética , Feminino , Genótipo , Humanos , Japão , Estilo de Vida , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Esforço FísicoRESUMO
The association of the Ser326Cys polymorphism of the 8-oxoguanine glycosylase 1 (OGG1) gene with type 2 diabetes was examined using a Japanese population (n (M/W): 4585 (2085/2500); age: 62.6 +/- 10.9 years). HbA1c levels and frequency of diabetic subjects were significantly higher in subjects with genotypes with Cys allele than in those without (p = 0.032 and 0.037, respectively). Multiple logistic regression analysis showed that genotypes with Cys allele were significantly associated with diabetes (OR: 1.32, p = 0.0289). In subjects whose glucose tolerance was classified by FPG and 2-h PG (n = 1.634), the association was more substantial (genotypes with Cys allele vs. without, OR: 1.70, p = 0.0059; genotypes Cys/Cys vs. Ser/Ser, OR: 2.19, p = 0.0008). In subjects with genotype Ser/Ser, the insulin secretion index, HOMA-beta, increased in the subjects with glucose intolerance and decreased in the subjects with diabetes, while, in subjects with genotypes Ser/Cys + Cys/Cys, HOMA-beta decreased as the glucose tolerance progressed (p for trend = 0.010).
Assuntos
DNA Glicosilases/genética , Diabetes Mellitus Tipo 2/genética , Predisposição Genética para Doença , Polimorfismo Genético , Idoso , Substituição de Aminoácidos , Povo Asiático/genética , Cisteína/genética , Diabetes Mellitus Tipo 2/metabolismo , Feminino , Humanos , Insulina/metabolismo , Secreção de Insulina , Masculino , Pessoa de Meia-Idade , Serina/genéticaRESUMO
To examine the association of the tumor necrosis factor-alpha (TNF-alpha) gene region with type 2 diabetes (DM), 11 single-nucleotide polymorphisms (SNPs) of the region were analyzed. The initial study using a sample set (148 cases vs. 227 controls) showed a significant association of the SNP IVS1G+123A of the TNF-alpha gene with DM (p=0.0056). Multiple logistic regression analysis using an enlarged sample set (225 vs. 716) revealed the significant association of the SNP with DM independently of any clinical traits examined (OR: 1.49, p=0.014). The functional relevance of the SNP were examined by the electrophoretic mobility shift assays using nuclear extracts from the U937 and NIH3T3 cells and luciferase assays in these cells with Simian virus 40 promoter- and TNF-alpha promoter-reporter gene constructs. The functional analyses showed that YY1 transcription factor bound allele-specifically to the SNP region and, the IVS1+123A allele had an increase in luciferase expression compared with the G allele.
Assuntos
Diabetes Mellitus Tipo 2/genética , Polimorfismo Genético , Fator de Necrose Tumoral alfa/genética , Idoso , Alelos , Animais , Povo Asiático/genética , Ensaio de Desvio de Mobilidade Eletroforética , Feminino , Genes Reporter , Humanos , Japão , Luciferases/genética , Masculino , Camundongos , Pessoa de Meia-Idade , Células NIH 3T3 , Regiões Promotoras Genéticas , Fator de Transcrição YY1/metabolismoRESUMO
The associations of five SNPs (SNPs1-5: A-5468G, A-3333G, C-1794T, C437T and T9148C) of the class II phosphoinositide 3-kinase gamma-subunit (PIK3C2G) gene with type 2 diabetes were examined using a population of the Takahata Study (n (M/W): 2930 (1328/1602); age: 63.3+/-10.2 years), a Japanese community-based study. Quantitative association study of the SNPs with HbA1c levels showed significant association for SNPs 2 and 4 (p=0.018 and 0.004, respectively). A case-control association study of SNP 4 with diabetes by multiple logistic regression analysis showed a significant association of the genotype TT of the SNP with an odds ratio of 2.21 (p=0.001) independently of age, gender and BMI. In the NGT subjects, serum fasting insulin levels in the at-risk genotype group of SNP 4 were significantly lower than those in the others (TT, TC, and CC, 4.9+/-2.6, 5.4+/-3.0, and 5.6+/-3.4muU/ml, respectively; p=0.029).
Assuntos
Diabetes Mellitus Tipo 2/genética , Fosfatidilinositol 3-Quinases/genética , Polimorfismo de Nucleotídeo Único , Idoso , Povo Asiático/genética , Estudos de Casos e Controles , Feminino , Humanos , Desequilíbrio de Ligação , Masculino , Pessoa de Meia-IdadeRESUMO
The associations of the C825T polymorphism (rs5443) of the G-protein beta3 subunit (GNB3) gene and eight adjacent single nucleotide polymorphisms (SNPs) with diabetes were examined using a Japanese population (n (M/W): 2956 (1335/1621); age: 63.0+/-10.2 years). Fasting plasma glucose (FPG) levels were significantly associated with the C825T polymorphism and two flanking SNPs (rs2301339 and rs5446) (p=0.002, 0.001, and 0.008, respectively). A case-control association study of the C825T polymorphism with diabetes using multiple logistic regression analysis showed a significant association of the genotypes TT+TC with an odds ratio of 0.62 (p=0.008) independent of age, gender, and BMI. The effects of salt consumption on the association were then examined (n=1635). The FPG levels were significantly associated with the C825T polymorphism only in subjects with low salt consumption (<12.44 g/day) (p=0.002). A case-control association study also showed a significant association with diabetes only in subjects with low salt consumption (p=0.006).
Assuntos
Diabetes Mellitus Tipo 2/etiologia , Predisposição Genética para Doença , Proteínas Heterotriméricas de Ligação ao GTP/genética , Polimorfismo de Nucleotídeo Único , Cloreto de Sódio na Dieta/administração & dosagem , Idoso , Povo Asiático/genética , Glicemia , Estudos de Casos e Controles , Estudos Transversais , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/genética , Jejum , Ligação Genética , Humanos , Japão/epidemiologia , Pessoa de Meia-IdadeRESUMO
Rats of the Jcl: Wistar-TgN (ARGHGEN) 1Nts strain (Mini rats) are transgenic animals carrying an antisense RNA transgene for rat growth hormone (GH); they show poor somatic growth and a low blood GH level compared to age-matched wild-type Wistar (non-Mini) rats. The purpose of the present study was to investigate age-related changes in growth hormone-immunoreactive (GH-IR) cells in the anterior pituitary gland (AP) of Mini rats at four, six, and eight weeks of age. The body weight and size of the GH-IR cells of Mini rats was significantly lower than that of non-Mini rats at six and eight weeks of age; however, this difference was not observed at four weeks of age. The AP volume and the number of GH-IR cells in Mini rats were significantly smaller than those of the age-matched non-Mini rats at the three ages. These results suggest that the abnormal development of GH-IR cells in the AP induced by the GH antisense RNA transgene is responsible for the poor somatic growth and the low blood GH levels in Mini rats.
Assuntos
Envelhecimento/metabolismo , Hormônio do Crescimento/metabolismo , Adeno-Hipófise/metabolismo , Envelhecimento/patologia , Animais , Animais Geneticamente Modificados , Hormônio do Crescimento/antagonistas & inibidores , Hormônio do Crescimento/genética , Imuno-Histoquímica , Masculino , Adeno-Hipófise/citologia , RNA Antissenso/genética , Ratos , Ratos WistarRESUMO
In September and October, 2004, an outbreak of encephalopathy of unknown etiology occurred in certain areas of Japan including Yamagata, Akita, and Niigata prefectures. These patients had a history of chronic renal failure, most of them had undergone hemodialysis, and also had a history of eating Sugihiratake (Pleurocybella porrigens), an autumn mushroom without known toxicity. Since clinical details of this type of encephalopathy remain unknown, we analyzed the clinical, radiological and electroencephalographic (EEG) features of ten cases of this encephalopathy in Yamagata prefecture. The summary of the present study is as follows: 1. Ten patients had chronic renal failure, and seven underwent hemodialysis. 2. Each patient had a history of eating Sugihiratake within 2-3 weeks of the onset of neurological symptoms. 3. The onset was subacute; the initial symptoms were tremor, dysarthria, and/or weakness of the extremities, which lasted an average of 4.5 days (ranging from 2 to 11 days), followed by severe consciousness disturbance and intractable seizures, resulting in status epilepticus in 5 patients. Myoclonus was also seen in 4 patients and Babinski reflex in 3. 4. Brain CT and MRI examinations were unremarkable in the early stages of the disease. Three to eight days after onset, however, conspicuous lesions appeared in the areas of the insula and basal ganglia in 6 patients. On MRI, these brain lesions were hyperintense on T2-weighted and FLAIR images, and hypointense on T1-weighted images. 5. EEG examination was performed in 6 patients, all of whom showed abnormal EEG findings. Periodic synchronous discharge (PSD) was seen in 2 patients, spike and wave complex in one patient, and non-specific slow waves in 3. 6. Prognosis was different from case to case. Three patients died at 13, 14, and 29 days after onset. Two patients still showed persistent disturbance of consciousness one month after onset. One patient showed parkinsonism after recovering from consciousness disturbance. Four patients recovered nearly completely around one month after onset In 3 of the 4 recovered patients, renal failure was not severe and they did not need to undergo hemodialysis. This suggests that the degree of renal failure is a key for the prognosis of this type of encephalopathy. The present study suggests that this endemic disease is a newly recognized clinical entity of encephalopathy.
Assuntos
Encefalopatias/etiologia , Surtos de Doenças , Falência Renal Crônica/complicações , Intoxicação Alimentar por Cogumelos/etiologia , Idoso , Idoso de 80 Anos ou mais , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Encefalopatias/diagnóstico , Eletroencefalografia , Feminino , Humanos , Falência Renal Crônica/terapia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Intoxicação Alimentar por Cogumelos/epidemiologia , Prognóstico , Diálise Renal , Tomografia Computadorizada por Raios XRESUMO
Plasma renin activity (PRA) is accepted as a marker for increased risk of cardiovascular diseases. However, the association between PRA and total mortality has not been fully explored in a general population. We here examined whether PRA is associated with increased total mortality in a general Japanese population. The participants of the Takahata study (3502 subjects; age, 62.5 ± 10.4 years), a population-based, longitudinal study of Japanese held from 2004 to 2006, were enrolled and followed up for up to 7 years. The incidence of death and causes of death were monitored annually to the end of 2010 (median follow-up, 2280 days). During the follow-up period, 143 subjects died. Kaplan-Meier analysis showed a significantly increased risk for total mortality in subjects with higher PRA (log-rank P < .001). Cox proportional hazard model analyses with adjustment for factors correlated with PRA (age, sex, weight, diastolic blood pressure, high-density lipoprotein cholesterol, uric acid, B-type natriuretic peptide, serum total protein, antihypertensive treatment, and diabetes) showed that higher PRA was associated with increased total mortality in linear regression models (per 1 increase in log 10 × PRA [nanograms per milliliter per hour]: hazard ratio, 2.12; 95% confidence interval, 1.47-3.06), between groups of patients stratified by quartiles of PRA (highest vs lowest quartile: 2.63, 1.57-4.41) and in subjects with high (≥ 2.0 ng/[mL h]) vs low (<2.0 ng/[mL h]) PRA (1.97, 1.37-2.83). Higher PRA was a significant and independent risk factor for increased total mortality in this Japanese population and may be a marker for subjects at an increased risk of total mortality.
Assuntos
Mortalidade , Renina/sangue , Pressão Sanguínea/fisiologia , Proteínas Sanguíneas/análise , Peso Corporal/fisiologia , Colesterol/sangue , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , Japão/epidemiologia , Estimativa de Kaplan-Meier , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Estudos Prospectivos , Ácido Úrico/sangueRESUMO
OBJECTIVE: To identify metabolites showing changes in serum levels among Japanese male with diabetes. METHODS: We performed metabolite profiling by coupling capillary electrophoresis with electrospray ionization time-of-flight mass spectrometry using fasting serum samples from Japanese male subjects with diabetes (n=17), impaired glucose tolerance (IGT; n=5) and normal glucose tolerance (NGT; n=14). RESULTS: Other than the expected differences in characteristics related to abnormal glucose metabolism, the percent body fat was significantly different among subjects with diabetes, IGT and NGT (27.3±6.2, 22.2±4.5 and 19.2±6.0%, respectively, p=0.0022). Therefore, percent body fat was considered as a possible confounding factor in subsequent analyses. Of 560 metabolites detected using our platform, the levels of 74 metabolites were quantified in all of the serum samples. Significant differences between diabetes and NGT were observed for 24 metabolites. The top-ranked metabolite was glycerol-3-phophate (glycerophosphate), which was significantly higher in subjects with diabetes than in those with NGT, even after Bonferroni correction for multiple testing (11.7±3.6 vs. 6.4±1.9 µM, respectively; corrected p=0.0222). Stepwise multiple regression analyses revealed that serum glycerophosphate levels were significantly correlated with 2-h plasma glucose after a 75-g oral glucose tolerance test (r=0.553, p=0.0005), independently of other characteristics, including FPG and HbA1c. CONCLUSION: Serum glycerophosphate levels were found to be elevated in Japanese men with diabetes, and correlated with 2-h PG, independent of FPG and HbA1c. Namely, serum glycerophosphate level at fasting condition can be a marker for predicting glucose intolerance. These results warrant further studies to evaluate the relevance of glycerophosphate in the pathophysiology of diabetes.
Assuntos
Diabetes Mellitus Tipo 2/sangue , Glicerofosfatos/sangue , Adiposidade , Idoso , Antropometria , Glicemia/análise , Pressão Sanguínea , Composição Corporal , Fatores de Confusão Epidemiológicos , Diabetes Mellitus Tipo 2/fisiopatologia , Eletroforese Capilar , Intolerância à Glucose/sangue , Teste de Tolerância a Glucose , Hemoglobinas Glicadas/análise , Humanos , Resistência à Insulina , Japão , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Período Pós-Prandial , Espectrometria de Massas por Ionização por ElectrosprayRESUMO
The association of the clusterin (CLU) gene polymorphism (single nucleotide polymorphisms [SNPs] 1-4: rs1532278, rs1532277, rs2279590, and rs2279591, respectively) with type 2 diabetes mellitus was examined using a population of the Funagata study (n [male-female] = 1631 [741:884]; age, 62.0 ± 12.1 years), a Japanese community-based study. Single nucleotide polymorphisms 1 to 3 were significantly associated with hemoglobin A(1c) levels (P = .0154, .0021, and .0006, respectively) and diabetes (.0310, .0170, and .0021, respectively). A case-control association study of SNP 3 with diabetes by multiple logistic regression analysis showed a significant association of genotype AA (the at-risk genotype) with an odds ratio (OR) of 2.33 (P = .0039) independently of age and sex. The association was marginally validated by a study with another Japanese community-based sample, the Takahata Study (n [male-female] = 2.948 [1333:1615]; age, 63.0 ± 10.2 years) (OR, 1.59; P = .0595; χ(2)P = .0264). When the 2 samples were combined, the association became more significant (OR, 1.75; P = .0025). In subjects with the non-at-risk genotypes, the insulin resistance index--homeostasis model assessment of insulin resistance (HOMA-R)--increased significantly (P < .0001) and the insulin secretion index--HOMA-ß--appeared to decrease (P = .1803 and .0097, respectively, for the genotypes AG and GG) as the glucose tolerance progressed toward diabetes (normal glucose tolerance to glucose intolerance to diabetes). However, in subjects with the at-risk genotype, HOMA-R and HOMA-ß showed a significant increase already in the subjects with normal glucose tolerance (P = .0239 and .0305, respectively); and as the glucose tolerance progressed toward diabetes, HOMA-R stayed approximately the same, whereas HOMA-ß decreased significantly (P = .0332). The CLU gene was associated with diabetes, probably through an increase in insulin resistance primarily and through an impairment of insulin secretion secondarily.
Assuntos
Clusterina/genética , Diabetes Mellitus Tipo 2/genética , Idoso , Índice de Massa Corporal , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Frequência do Gene , Genótipo , Humanos , Hipertensão/complicações , Hipertensão/genética , Insulina/metabolismo , Resistência à Insulina/genética , Resistência à Insulina/fisiologia , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético/genética , Polimorfismo de Nucleotídeo Único , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
The predictive value of hemoglobin A1c (HbA1c) in comparison to fasting plasma glucose (FPG) is evaluated for 5-year incident diabetes (DM), as HbA1c may be more practical than FPG in the screening for DM in the future. Of 1189 non-DM subjects aged 35-89 years old from the Funagata Study, 57 subjects (4.8%) had developed DM on the WHO criteria at 5-year follow-up. The odds ratio (95% confidence interval: CI) for a one standard deviation increase in FPG/HbA1c was 3.40 (2.44-4.74)/3.49 (2.42-5.02). The area under the receiver operating characteristic curve for FPG/HbA1c was 0.786 (95% CI: 0.719-0.853)/0.785 (0.714-0.855). The HbA1c corresponding to FPG 5.56 mmol/l was HbA1c 5.3%. There was no statistical difference in sensitivity between FPG 5.56 mmol/l and HbA1c 5.3% (61.4% vs. 56.1%), while specificity was higher in HbA1c 5.3% than FPG 5.56 mmol/l (87.8% vs. 82.5%, p-value<0.001). The fraction of incident case from those with baseline IGT was similar between the groups, however the fraction of people above the cut-off was significantly lower in HbA1c 5.3% than FPG 5.56 mmol/l (14.3% vs. 19.6%, p-value<0.001). HbA1c is similar to FPG to evaluate DM risk, and HbA1c could be practical and efficient to select subjects for intervention.
Assuntos
Glicemia/análise , Diabetes Mellitus/sangue , Hemoglobinas Glicadas/análise , Adulto , Idoso , Idoso de 80 Anos ou mais , Glicemia/metabolismo , Pressão Sanguínea , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/fisiopatologia , Progressão da Doença , Jejum , Feminino , Seguimentos , Teste de Tolerância a Glucose , Hemoglobinas Glicadas/metabolismo , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Curva ROC , Sensibilidade e EspecificidadeAssuntos
Anti-Hipertensivos/administração & dosagem , Tronco Encefálico/patologia , Hipertensão/complicações , Encefalopatia Hipertensiva/diagnóstico , Imageamento por Ressonância Magnética/métodos , Quimioterapia Combinada , Seguimentos , Humanos , Hipertensão/diagnóstico , Hipertensão/tratamento farmacológico , Encefalopatia Hipertensiva/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Medição de Risco , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
Raised FPG was better at identifying future diabetes than either IDF MetS or a constellation of risk factors except for raised FPG with and without abdominal adiposity. This should shed light on a screening program for future DM in Japan.