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BACKGROUND: Overeating and inactivity are associated with type 2 diabetes. This study aimed to investigate its pathological basis using integrated omics and db/db/mice, a model representing this condition. METHODS: The study involved housing 8-week-old db/m and db/db mice for 8 weeks. Various analyses were conducted, including gene expression in skeletal muscle and small intestine using next-generation sequencing; cytokine arrays of serum; assessment of metabolites in skeletal muscle, stool, and serum; and analysis of the gut microbiota. Histone modifications in small intestinal epithelial cells were profiled using CUT&Tag. RESULTS: Compared with db/m mice, db/db mice had 22.4% lower grip strength and approximately five times the visceral fat weight (P < 0.0001). Serum cytokine arrays showed a 2.8-fold relative concentration of VEGF-A in db/db mice (P < 0.0001) and lower concentrations of several other cytokines. mRNA sequencing revealed downregulation of Myh expression in skeletal muscle, upregulation of lipid and glucose transporters, and downregulation of amino acid transporters in the small intestine of db/db/mice. The concentrations of saturated fatty acids in skeletal muscle were significantly higher, and the levels of essential amino acids were lower in db/db mice. Analysis of the gut microbiota, 16S rRNA sequencing, revealed lower levels of the phylum Bacteroidetes (59.7% vs. 44.9%) and higher levels of the phylum Firmicutes (20.9% vs. 31.4%) in db/db mice (P = 0.003). The integrated signal of histone modifications of lipid and glucose transporters was higher, while the integrated signal of histone modifications of amino acid transporters was lower in the db/db mice. CONCLUSIONS: The multi-omics approach provided insights into the epigenomic alterations in the small intestine, suggesting their involvement in the pathogenesis of inactivity-induced muscle atrophy in obese mice.
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BACKGROUND: Sarcopenic obesity, a combination of sarcopenia and obesity, is a pathological feature of type 2 diabetes. Several human studies have shown that milk is useful in the prevention of sarcopenia. This study was aimed at clarifying the effect of milk on the prevention of sarcopenic obesity in db/db mice. METHODS: A randomized and investigator-blinded study was conducted using male db/db mice. Eight-week-old db/db mice were housed for 8 weeks and fed milk (100 µL/day) using a sonde. The faecal microbiota transplantation (FMT) group received antibiotics for 2 weeks, starting at 6 weeks of age, followed by FMT twice a week until 16 weeks of age. RESULTS: Milk administration to db/db mice increased grip strength (Milk-: 164.2 ± 4.7 g, Milk+: 230.2 ± 56.0 g, P = 0.017), muscle mass (soleus muscle, Milk-: 164.2 ± 4.7 mg, Milk+: 230.2 ± 56.0 mg, P < 0.001; plantaris muscle, Milk-: 13.3 ± 1.2 mg, Milk+: 16.0 ± 1.7 mg, P < 0.001) and decreased visceral fat mass (Milk-: 2.39 ± 0.08 g, Milk+: 1.98 ± 0.04 mg, P < 0.001), resulting in a significant increase in physical activity (light: P = 0.013, dark: P = 0.034). FMT from mice fed milk not only improved sarcopenic obesity but also significantly improved glucose intolerance. Microarray analysis of gene expression in the small intestine revealed that the expression of amino acid absorption transporter genes, namely, SIc7a5 (P = 0.010), SIc7a1 (P = 0.015), Ppp1r15a (P = 0.041) and SIc7a11 (P = 0.029), was elevated in mice fed milk. In 16S rRNA sequencing of gut microbiota, the genus Akkermansia was increased in both the mice fed milk and the FMT group from the mice fed milk. CONCLUSIONS: The findings of this study suggest that besides increasing the intake of nutrients, such as amino acids, milk consumption also changes the intestinal environment, which might contribute to the mechanism of milk-induced improvement of sarcopenic obesity.
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Diabetes Mellitus Tipo 2 , Sarcopenia , Animais , Masculino , Camundongos , Akkermansia , Fezes , Leite , Obesidade/complicações , RNA Ribossômico 16S , Sarcopenia/prevenção & controleRESUMO
INTRODUCTION: Brazilian green propolis is an important honeybee product that is considered beneficial for health. Here, we examined the therapeutic potential of dietary supplementation with propolis against sarcopenic obesity using Db/Db mice. METHODS: Db/m mice fed a normal diet alone and Db/Db mice fed normal diet alone, or supplemented with different amounts of propolis (0.08, 0.4 and 2%), were examined for effects on sarcopenic obesity. RESULTS: Propolis improved the glucose tolerance (P < 0.001), increased the grip strength (P < 0.001) and the weight of soleus (P = 0.006) and plantaris muscles (P = 0.008). Moreover, propolis improved the non-alcoholic fatty liver disease activity score (P < 0.001) and decreased the expression of genes related to inflammation, liver fibrosis and fatty acid metabolism. Propolis decreased the accumulation of saturated fatty acids in the liver and increased their excretion in faeces. With regard to the innate immunity, propolis decreased the ratio of M1 macrophages (P = 0.008) and Type 1 and 3 innate lymphoid cells to CD45-positive cells (P < 0.001) and increased the ratio of M2 macrophages (P = 0.002) and ILC2s (P = 0.007) in the liver. Additionally, propolis decreased the expression of genes related to muscle atrophy and inflammation and the concentration of saturated fatty acids in the soleus muscle. 16S rRNA phylogenetic sequencing revealed that propolis increased the Bacteroidetes/Firmicutes ratio, and the abundance of Butyricicoccus and Acetivibrio genera. Gut microbiota related to the pentose phosphatase pathway and glycerolipid metabolism was more prevalent after the administration of propolis. CONCLUSIONS: This is the first study to demonstrate that propolis can improve sarcopenic obesity by improving dysbiosis due to overeating and provides new insights into diet-microbiota interactions during sarcopenic obesity.
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Imunidade Inata , Própole , Camundongos , Abelhas , Animais , Própole/farmacologia , Própole/uso terapêutico , Dieta Hiperlipídica , RNA Ribossômico 16S , Filogenia , Linfócitos/metabolismo , Disbiose/tratamento farmacológico , Obesidade/tratamento farmacológico , Ácidos GraxosRESUMO
INTRODUCTION: Sarcopenia index (SI), calculated by (serum creatinine/cystatin C)×100, is reported to be associated with sarcopenia. Few studies reported the association between SI and subclinical atherosclerosis. We evaluated the association between SI and subclinical atherosclerosis, assessed by brachial-ankle pulse wave velocity (baPWV). RESEARCH DESIGN AND METHODS: One hundred seventy-four patients with type 2 diabetes were included in this cross-sectional study. The relationship between SI and baPWV was assessed by Pearson's correlation coefficient. To calculate area under the receiver operator characteristic (ROC) curve (AUC) of SI for the presence of subclinical atherosclerosis, which was defined as baPWV >1800 cm/s, ROC analysis was performed. Logistic regression analyses were performed to assess the effect of SI on the prevalence of subclinical atherosclerosis adjusting for covariates. RESULTS: Mean age, duration of diabetes, baPWV, and SI were 66.9 (10.1) years, 17.7 (11.6) years, 1802 (372) cm/s, and 77.6 (15.8), respectively. There was an association between SI and baPWV (men; r=-0.25, p=0.001, and women; r=-0.37, p=0.015). The optimal cut-off point of SI for the presence of subclinical atherosclerosis was 77.4 (sensitivity=0.72, specificity=0.58, p<0.001, AUC 0.66 (95% CI: 0.57 to 0.74)). In addition, SI was associated with the prevalence of subclinical atherosclerosis (adjusted OR 0.95, 95% CI: 0.91 to 0.99, p=0.015). CONCLUSIONS: SI is associated with the prevalence of subclinical atherosclerosis in patients with type 2 diabetes.
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Aterosclerose , Diabetes Mellitus Tipo 2 , Sarcopenia , Idoso , Índice Tornozelo-Braço , Aterosclerose/diagnóstico , Aterosclerose/epidemiologia , Aterosclerose/etiologia , Creatinina/sangue , Estudos Transversais , Cistatina C/sangue , Diabetes Mellitus Tipo 2/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Onda de PulsoRESUMO
BACKGROUND: Diabetes mellitus increases the excretion of urinary glucose from the renal glomeruli due to elevated blood glucose levels. In the renal tubules, SGLT2 is expressed and reabsorbs the excreted urinary glucose. In the pathogenesis of diabetes mellitus, glucose reabsorption by SGLT2 is increased, and SGLT2 inhibitors improve hyperglycaemia by inhibiting this reabsorption. When urinary glucose excretion is enhanced, glucose supply to skeletal muscle may be insufficient and muscle protein catabolism may be accelerated. On the other hand, SGLT2 inhibitors not only ameliorate hyperglycaemia but also improve fatty acid metabolism in muscle, which may prevent muscle atrophy. METHODS: Eight-week-old male db/m mice or db/db mice were fed a standard diet with or without the SGLT2i luseogliflozin (0.01% w/w in chow) for 8 weeks. Mice were sacrificed at 16 weeks of age, and skeletal muscle and serum lipidomes, as well as skeletal muscle transcriptome, were analysed. RESULTS: Administration of SGLT2i led to not only decreased visceral fat accumulation (P = 0.004) but also increased soleus muscle weight (P = 0.010) and grip strength (P = 0.0001). The levels of saturated fatty acids, especially palmitic acid, decreased in both muscles (P = 0.017) and sera (P = 0.041) upon administration of SGLT2i, while the content of monosaturated fatty acids, especially oleic acid, increased in both muscle (P < 0.0001) and sera (P = 0.009). Finally, the accumulation of transcripts associated with fatty acid metabolism, such as Scd1, Fasn, and Elovl6, and of muscle atrophy-associated transcripts, such as Foxo1, Mstn, Trim63, and Fbxo32, decreased following SGLT2i administration. CONCLUSIONS: Intramuscular fatty acid metabolism and gene expression were influenced by the extracellular lipidome, which was modified by SGLT2i. Hence, secondary effects, other than the hypoglycaemic effects of SGLT2i, might lead to the alleviation of sarcopenia.
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Inibidores do Transportador 2 de Sódio-Glicose , Animais , Lipidômica , Masculino , Camundongos , Músculo Esquelético , Atrofia Muscular , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Sorbitol/análogos & derivadosRESUMO
Background: Sarcopenia has reportedly been associated with increased risk of mortality in general populations. However, few studies have investigated the association between sarcopenia and mortality in older people with type 2 diabetes mellitus (T2D). This study aimed to investigate the effect of sarcopenia on incident all-cause mortality in older people with T2D. Methods: Low muscle strength were set at handgrip strength <28 kg for men and <18 kg for women, and low skeletal muscle mass index (SMI), evaluated using the impedance body composition analyzer, were set at SMI <7.0 kg/m2 for men and <5.7 kg/m2 for women. People who had both low muscle strength and low SMI were diagnosed with sarcopenia. Due to a low incidence of all-cause mortality, the propensity score was used. The propensity score was evaluated using multivariable logistic regression models with the following parameters: age, sex, duration of diabetes, history of heart disease, history of cancer, smoking, exercise, alcohol, sodium-glucose cotransporter-2 inhibitor, glucagon-like peptide-1 receptor agonist, insulin, corticosteroid, hypertension, body mass index, glycosylated hemoglobin A1c, triglycerides, and creatinine, and the C-statistic was 0.89. Results: In this prospective cohort study, 396 people with an average age and duration of diabetes of 71.3 (6.3) years and 16.3 (11.3) years, respectively, were included. Of those included, 14.6% had sarcopenia. During the average 40.5 (16.5) months of follow-up, 13 people (6 out of the 338 without sarcopenia and 7 out of the 58 with sarcopenia) died. Incident rate were 5.1/1000 person years of follow-up in people without sarcopenia and 41.3/1000 person years of follow-up in people with sarcopenia. According to Cox regression analysis, sarcopenia was associated with all-cause mortality (adjusted hazard ratio: 6.12, 95% confidence interval: 1.52-24.7, p = 0.011). Conclusion: Sarcopenia is associated with incident all-cause mortality in older outpatients with T2D.
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Diabetes Mellitus Tipo 2/mortalidade , Diabetes Mellitus Tipo 2/fisiopatologia , Sarcopenia/mortalidade , Sarcopenia/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Diabetes Mellitus Tipo 2/diagnóstico , Feminino , Seguimentos , Força da Mão/fisiologia , Humanos , Masculino , Mortalidade/tendências , Força Muscular/fisiologia , Estudos Prospectivos , Fatores de Risco , Sarcopenia/diagnósticoRESUMO
The aim of this prospective cohort study was to examine the relationships between the intakes of various vitamins and the loss of muscle mass in older people with type 2 diabetes (T2DM). The change in skeletal muscle mass index (SMI, kg/m2) (kg/m2/year) was defined as follows: (SMI at baseline (kg/m2) - SMI at follow-up (kg/m2))/follow-up period (year). The rate of SMI reduction (%) was calculated as follows (the change in SMI (kg/m2/year)/SMI at baseline (kg/m2)) × 100. The rate of SMI reduction ≥ 1.2% was considered as the loss of muscle mass. Among 197 people with T2DM, 47.2% of them experienced the loss of muscle mass at the 13.7 ± 5.2 month follow-up. Vitamin B1 (0.8 ± 0.3 vs. 0.8 ± 0.3 mg/day, p = 0.031), vitamin B12 (11.2 ± 8.3 vs. 13.4 ± 7.5 µg/day, p = 0.049), and vitamin D (16.5 ± 12.2 vs. 21.6 ± 13.0 µg/day, p = 0.004) intakes in people with the loss of muscle mass were significantly lower than those without. Vitamin D intake was related to the loss of muscle mass after adjusting for sex, age, exercise, alcohol, smoking, body mass index, SMI, glucagon-like peptide-1 agonist, sodium glucose cotransporter-2 inhibitor, insulin, HbA1c, creatinine, energy intake, and protein intake (adjusted odds ratio 0.93, 95% confidence interval: 0.88-0.97, p = 0.003). This study showed that vitamin D intake was related to the loss of muscle mass in older people with T2DM. Vitamin B12 intake tended to be related to the loss of muscle mass, although vitamin A, vitamin B2, vitamin B6, vitamin C, and vitamin E intake were not related.
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Diabetes Mellitus Tipo 2/fisiopatologia , Dieta/efeitos adversos , Estado Nutricional , Sarcopenia/epidemiologia , Vitaminas/análise , Idoso , Diabetes Mellitus Tipo 2/complicações , Dieta/estatística & dados numéricos , Inquéritos sobre Dietas , Ingestão de Energia/fisiologia , Feminino , Humanos , Japão/epidemiologia , Masculino , Músculo Esquelético/fisiopatologia , Estudos Prospectivos , Sarcopenia/etiologiaRESUMO
BACKGROUND: Hepatic steatosis has a pivotal role in the development of chronic liver diseases, even in alcohol-related liver disease. Alcoholic fatty liver disease is an important phenotype among alcohol-related liver diseases. While metabolic syndrome is a dominant risk factor of incident nonalcoholic fatty liver disease, the role of metabolic syndrome in alcoholic fatty liver disease has not been clarified yet. METHODS: A retrospective cohort study was performed at a health check-up center in Japan. Subjects consisted of male participants without fatty liver who consumed ethanol of 420 g/week or higher. Adjusted hazard ratios and 95% confidence intervals at the baseline examinations for incident alcoholic fatty liver disease were estimated using Cox model. RESULTS: A total of 640 participants were included in this study. During 3.91 years (IQR 1.63-7.09) of follow-up, 168 new cases of alcoholic fatty liver disease developed (49.1 cases per 1000 persons per year). After adjustment for age, smoking status, alcohol consumption, the hazard ratio for a 1 kg/m2 increase in body mass index was 1.2 (1.12-1.28). The hazard ratio of subjects with high triglyceride and low high-density lipoprotein-cholesterol levels were 1.56 (1.12-2.18) and 1.52 (1.03-2.25), respectively. CONCLUSIONS: Obesity, high triglyceridemia, and low high-density lipoprotein-cholesterolemia are independent risk factors of alcoholic fatty liver disease in Japanese men who consumed alcohol habitually. In people with these risks, triglyceride lowering and high-density lipoprotein-cholesterol raising by improving insulin resistance and weight maintenance in addition to abstinence from alcohol would be effective in preventing the development of alcoholic fatty liver disease.
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Fígado Gorduroso Alcoólico , Síndrome Metabólica , Hepatopatia Gordurosa não Alcoólica , Fígado Gorduroso Alcoólico/epidemiologia , Humanos , Masculino , Síndrome Metabólica/complicações , Síndrome Metabólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Obesidade/complicações , Obesidade/epidemiologia , Estudos Retrospectivos , Fatores de RiscoRESUMO
Background and aims: Group 2 innate lymphoid cells (ILC2s) have been implicated in the regulation of metabolic homeostasis in mice. Methods: In this study, the role of ILC2s in white adipose tissue (WAT) was investigated using ST2, an IL-33 receptor that is expressed on ILC2 knockout mice. Results: The deficiency of ST2 decreased ILC2s in WAT, whereas ex-ILC2, which acquired group 1 innate lymphoid cell (ILC1)-like traits, was increased. This led to significant metabolic disorders such as visceral fat obesity, decreased browning in WAT, reduction of energy metabolism, and impaired glucose tolerance, compared to wild type (WT) mice. Those metabolic abnormalities of ST2-knockout (ST2KO) mice were not ameliorated by IL-33 administration, but impaired glucose tolerance and visceral fat obesity were significantly improved by transplantation of ILCs from the bone marrow of WT mice. The relative expression of Cd36 in WAT increased due to the deficiency of ST2, and the storage of saturated fatty acids in WAT of ST2KO mice was significantly higher than that of WT mice. Moreover, saturated fatty acids aggravated the chronic inflammation in adipocytes, promoted the differentiation of M1-like macrophages, and inhibited that of M2-like macrophages. Conclusions: Our results indicated that ILC2 regulates diet-induced obesity and chronic inflammation through the regulation of saturated fatty acid absorption in visceral adipose tissue.
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Glicemia/metabolismo , Ácidos Graxos/metabolismo , Intolerância à Glucose/metabolismo , Imunidade Inata , Resistência à Insulina , Gordura Intra-Abdominal/metabolismo , Linfócitos/metabolismo , Absorção Fisiológica , Transferência Adotiva , Animais , Glicemia/efeitos dos fármacos , Antígenos CD36/metabolismo , Intolerância à Glucose/tratamento farmacológico , Intolerância à Glucose/genética , Intolerância à Glucose/imunologia , Homeostase , Imunidade Inata/efeitos dos fármacos , Inflamação/imunologia , Inflamação/metabolismo , Mediadores da Inflamação/metabolismo , Proteína 1 Semelhante a Receptor de Interleucina-1/genética , Proteína 1 Semelhante a Receptor de Interleucina-1/metabolismo , Interleucina-33/farmacologia , Gordura Intra-Abdominal/efeitos dos fármacos , Gordura Intra-Abdominal/imunologia , Linfócitos/efeitos dos fármacos , Linfócitos/imunologia , Macrófagos/imunologia , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Obesidade/imunologia , Obesidade/metabolismo , Células RAW 264.7RESUMO
Background and Aims: Many nutritional and epidemiological studies have shown that high consumption of trans fatty acids can cause several adverse effects on human health, including cardiovascular disease, diabetes, and cancer. In the present study, we investigated the effect of trans fatty acids on innate immunity in the gut by observing mice fed with a diet high in trans fatty acids, which have been reported to cause dysbiosis. Methods: We used C57BL6/J mice and fed them with normal diet (ND) or high-fat, high-sucrose diet (HFHSD) or high-trans fatty acid, high-sucrose diet (HTHSD) for 12 weeks. 16S rRNA gene sequencing was performed on the mice stool samples, in addition to flow cytometry, real-time PCR, and lipidomics analysis of the mice serum and liver samples. RAW264.7 cells were used for the in vitro studies. Results: Mice fed with HTHSD displayed significantly higher blood glucose levels and advanced fatty liver and intestinal inflammation, as compared to mice fed with HFHSD. Furthermore, compared to mice fed with HFHSD, mice fed with HTHSD displayed a significant elevation in the expression of CD36 in the small intestine, along with a reduction in the expression of IL-22. Furthermore, there was a significant increase in the populations of ILC1s and T-bet-positive ILC3s in the lamina propria in mice fed with HTHSD. Finally, the relative abundance of the family Desulfovibrionaceae, which belongs to the phylum Proteobacteria, was significantly higher in mice fed with HFHSD or HTHSD, than in mice fed with ND; between the HFHSD and HTHSD groups, the abundance was slightly higher in the HTHSD group. Conclusions: This study revealed that compared to saturated fatty acid intake, trans fatty acid intake significantly exacerbated metabolic diseases such as diabetes and fatty liver.
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Glicemia/efeitos dos fármacos , Dieta Hiperlipídica/efeitos adversos , Enterite/induzido quimicamente , Intolerância à Glucose/induzido quimicamente , Imunidade Inata/efeitos dos fármacos , Intestino Delgado/efeitos dos fármacos , Linfócitos/efeitos dos fármacos , Ácidos Graxos trans/toxicidade , Animais , Glicemia/metabolismo , Antígenos CD36/metabolismo , Sacarose Alimentar/toxicidade , Disbiose , Enterite/imunologia , Enterite/metabolismo , Enterite/microbiologia , Microbioma Gastrointestinal/efeitos dos fármacos , Intolerância à Glucose/sangue , Intolerância à Glucose/imunologia , Interleucinas/metabolismo , Intestino Delgado/imunologia , Intestino Delgado/metabolismo , Intestino Delgado/microbiologia , Fígado/efeitos dos fármacos , Fígado/imunologia , Fígado/metabolismo , Linfócitos/imunologia , Linfócitos/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/induzido quimicamente , Hepatopatia Gordurosa não Alcoólica/imunologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Células RAW 264.7 , Interleucina 22RESUMO
Background and Aims: Emerging evidence has revealed that innate lymphoid cells (ILCs) play a key role in regulating metabolic disorders. Here, we investigated the role of group 3 ILCs (ILC3s) in the modulation of Non-alcoholic fatty liver disease (NAFLD). Methods: RORγ gfp/gfp (RORgt KI/KI) and Rag2-/- mice with the administration of A213, RORgt antagonist, fed with a high-fat-diet (HFD) for 12 weeks, were used. We performed flow cytometry, real time PCR, and lipidomics analysis of serum and liver, and used RAW264.7 cells and murine primary hepatocytes in vitro. Results: HFD increased ILC3s and M1 macrophages in the liver, and RORgt KI/KI mice deficient in ILC3 showed significant fatty liver, liver fibrosis and significantly increased palmitic acid levels in serum and liver. In addition, administration of A213 to Rag2-/- mice caused significant fatty liver, liver fibrosis, and a significant increase in serum and liver palmitate concentrations, as in RORgt KI/KI mice. Addition of palmitc acid stimulated IL-23 production in cell experiments using RAW264.7. IL-22 produced by ILC3s inhibited the palmitate-induced apoptosis of primary hepatocytes. Conclusions: HFD stimulates IL-23 production by M1 macrophages, thus promoting ILC3 proliferation, whereas IL-22 secreted by ILC3s contributes to the upregulation of hepatic lipid metabolism and has anti-apoptosis activity.
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Fígado Gorduroso/imunologia , Imunidade Inata/imunologia , Fígado/imunologia , Linfócitos/imunologia , Macrófagos/imunologia , Animais , Apoptose/imunologia , Células Cultivadas , Dieta Hiperlipídica/efeitos adversos , Fígado Gorduroso/etiologia , Fígado Gorduroso/metabolismo , Hepatócitos/citologia , Hepatócitos/imunologia , Fígado/metabolismo , Fígado/patologia , Linfócitos/metabolismo , Macrófagos/classificação , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Ácido Palmítico/sangue , Ácido Palmítico/imunologia , Ácido Palmítico/metabolismo , Substâncias Protetoras/metabolismo , Células RAW 264.7RESUMO
BACKGROUND & AIM: Past studies reported that the intake of adequate energy is more important than protein intake; however, the relationship between energy intake and muscle mass loss remains unclear thus far. This study therefore explored the association between energy intake and muscle mass loss in people with type 2 diabetes (T2D). METHODS: In this prospective cohort study, impedance body composition and a brief-type self-administered diet history questionnaire were used for analyzing body composition and habitual diet intake, respectively. Skeletal muscle mass index (SMI, kg/m2) was defined as appendicular muscle mass (kg) ÷ height-squared (m2). Rate of SMI change (%) was calculated as ([SMI at baseline - SMI at follow-up]/[follow-up duration (years) × baseline SMI (kg/m2)]) × 100, and muscle mass loss was defined as rate of SMI change ≥0.5%. Energy intake was defined as total energy intake (kcal/day) divided by ideal body weight (kg), defined as 22 × patient height-squared (m2). RESULTS: Among non-older and older participants, 54.8% (n = 51/93) and 58.9% (n = 116/197) experienced muscle mass loss at 16.3 (6.4) and 18.1 (7.1) months' follow-up, respectively. Logistic regression analyses showed that energy intake was associated with incident muscle mass loss after adjusting for age, sex, insulin, sodium glucose cotransporter-2 inhibitor, glucagon-like peptide-1 agonist, steroids, smoking, exercise, alcohol intake, body mass index, SMI, presence of renal failure, and protein intake (g/actual body weight/day) in the older people (odds ratio [OR] 0.94 [95% confidence interval [CI] 0.88-0.996], p = 0.037), whereas energy intake was not associated with incident muscle mass loss in the non-older people (OR 0.96 [95% CI 0.86-1.06], p = 0.423). CONCLUSIONS: Insufficient energy intake is associated with muscle mass loss in older people with T2D. Therefore, it is recommended to consume enough energy for older people with T2D to keep muscle mass.
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Índice de Massa Corporal , Diabetes Mellitus Tipo 2/fisiopatologia , Dieta/efeitos adversos , Ingestão de Energia/fisiologia , Sarcopenia/etiologia , Composição Corporal , Peso Corporal , Diabetes Mellitus Tipo 2/complicações , Inquéritos sobre Dietas , Proteínas Alimentares/análise , Impedância Elétrica , Comportamento Alimentar/fisiologia , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/fisiopatologia , Estudos ProspectivosRESUMO
BACKGROUND: Colorectal cancer (CRC), which is related with insulin resistance, is a one of the most common cancers. Triglyceride-glucose index (TyG index) was made for a marker of insulin resistance. We conducted the investigation of association between TyG index and incident CRC. METHODS: We examined the affect of TyG index on incident CRC in this historical cohort study of 27,944 (16,454 men and 11,490 women) participants. TyG index was calculated as ln [fasting triglycerides (mg/dL) × fasting plasma glucose (mg/dL)/2]. The impact of TyG index on incident CRC was investigated using Cox proportional hazard models, adjusting for sex, age, body mass index, smoking status, alcohol consumption, exercise, systolic blood pressure and creatinine. The covariate-adjusted receiver operating characteristic (ROC) curve calculated the area under the curve (AUC) and cut-off value of TyG index for the incidence of CRC. RESULTS: During the median 4.4-year follow-up, 116 participants were diagnosed as CRC. The cumulative incidence rate of CRC were 0.4%. In Cox proportional hazard model, the HRs of TyG index were 1.38 (95% Confidence interval (CI), 1.00-1.91, p = 0.049) after adjusting for covariates. In the covariate-adjusted ROC curve analysis, the cut-off value of TyG index for incident CRC was 8.272 (AUC 0.687 (95%CI, 0.637-737, sensitivity = 0.620, specificity = 0.668, p < 0.001)). CONCLUSIONS: TyG index can predict the onset of CRC. For early detection of CRC, we should encourage people with high TyG index to undergo screening for CRC.
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Glicemia/análise , Neoplasias Colorretais/diagnóstico , Triglicerídeos/sangue , Adenocarcinoma/sangue , Adenocarcinoma/diagnóstico , Adenocarcinoma/epidemiologia , Adulto , Biomarcadores/sangue , Glicemia/metabolismo , Estudos de Coortes , Neoplasias Colorretais/sangue , Neoplasias Colorretais/epidemiologia , Detecção Precoce de Câncer , Feminino , Indicadores Básicos de Saúde , Humanos , Incidência , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos RetrospectivosRESUMO
OBJECTIVE: The Visceral Adiposity Index (VAI) is a marker of visceral fat accumulation and dysfunction. We aimed to investigate the association between VAI and incident colorectal cancer (CRC). DESIGN: In this historical cohort study of 27 921 (16 434 men and 11 487 women) participants, we divided the participants into tertiles according to VAI. We calculated VAI: men, VAI = (waist circumference (WC)/(39.68+1.88 × body mass index (BMI))) × (triglycerides (TG)/1.03) × (1.31/high-density lipoprotein cholesterol (HDL)); women, VAI = (WC/(36.58+1.89 × BMI)) × (TG/0.81) × (1.52/HDL). We performed Cox proportional hazard models, adjusting for sex, age, smoking, alcohol consumption, exercise, haemoglobin A1c and systolic blood pressure. RESULTS: During the median 4.4-year follow-up, 116 participants developed CRC. Compared with the lowest tertile, the HRs of incident CRC in the middle and the highest tertiles were 1.30 (95% CI 0.76 to 2.28, p=0.338) and 2.41 (1.50 to 4.02, p<0.001) in univariate analysis. Moreover, the HRs of incident CRC in the middle and the highest tertiles were 1.27 (0.73 to 2.23, p=0.396) and 1.98 (1.15 to 3.39, p=0.013) after adjusting for covariates. CONCLUSIONS: VAI can be a predictor of incident CRC. For early detection, we should encourage people with high VAI to undergo screening for CRC.
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HDL-Colesterol/sangue , Gordura Intra-Abdominal/patologia , Obesidade Abdominal/patologia , Triglicerídeos/sangue , Adulto , Índice de Massa Corporal , Estudos de Coortes , Neoplasias Colorretais/epidemiologia , Feminino , Humanos , Incidência , Gordura Intra-Abdominal/metabolismo , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Obesidade Abdominal/complicações , Obesidade Abdominal/epidemiologia , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Circunferência da Cintura/fisiologiaRESUMO
Omega-3 fatty acids intake is important to maintain muscle mass. However, the relationship between omega-3 fatty acids intake and sarcopenia in elderly patients with type 2 diabetes has been unclear. We used the brief-type self-administered diet history questionnaire for the assessment of habitual food and nutrient intake. Body composition of patients was evaluated using bioimpedance analysis. To investigate the effect of energy intake on the presence of sarcopenia, we performed logistic regression analyses. Among the patients, 45 patients (13.2%) were diagnosed as sarcopenia. Patients with sarcopenia were aged [74.2 (5.7) vs 71.4 (5.9) years, p = 0.003] and lower body mass index [21.2 (3.5) vs 24.3 (4.6) kg/m2, p<0.001] than those without. In addition, omega-3 fatty acids intake of patients with sarcopenia was lower than that without [2.6 (1.0) vs 3.0 (1.2) kcal/day, p = 0.046]. Omega-3 fatty acids intake was negatively associated with the presence of sarcopenia (odds ratio: 0.29, 95% confidence interval: 0.14-0.60, p<0.001) after adjusting for age, sex, exercise, smoking status, diabetes duration, hemoglobin A1c, energy intake, protein intake, fat intake and omega-3 fatty acids intake. Omega-3 fatty acids intake was negatively associated with the presence of sarcopenia in elderly patients with type 2 diabetes.
RESUMO
BACKGROUND AND AIMS: Visceral adiposity index (VAI), calculated with body mass index, high-density lipoprotein cholesterol, triglyceride and waist circumference, has been proposed as a marker of visceral fat accumulation and dysfunction. METHODS: The impact of VAI on incident nonalcoholic fatty liver disease (NAFLD) in a historical cohort study of 8399 (3773 men and 4626 women) participants. NAFLD was defined as having fatty liver diagnosed by abdominal ultrasonography. We divided the participants into two groups according to sex and into quartiles according to VAI (Q1-4). We calculated VAI using the formulas. Men: VAI = [waist circumference (WC)/39.68 + (1.88 × body mass index [BMI])] × [triglycerides (TG)/1.03] × [1.31/high-density lipoprotein cholesterol (HDL)]; women: VAI = [WC/36.58 + (1.89 × BMI)] × (TG/0.81) × (1.52/HDL). We performed Cox proportional hazard models, adjusting for age, alanine aminotransferase, fasting plasma glucose, systolic blood pressure, alcohol consumption, smoking status and exercise. RESULTS: During the median 4.5-year follow-up for men and 4.9-year follow-up for women, 1078 participants (737 men and 341 women) developed NAFLD. The 4000 days cumulative incidence rate of NAFLD for men and women were 7.5% and 2.2% in Q1, 14.5% and 4.0% in Q2, 22.3% and 6.7% in Q3 and 33.8% and 16.7% in Q4. The hazard ratios of incident NAFLD in Q4 (VAI: men, > 1.13; women, > 0.83) were 3.69 (95% confidence interval 2.84-4.86, P < 0.001) in men and 4.93 (3.28-7.73, P < 0.001) in women, compared to Q1 (VAI: men, < 0.44; women, < 0.36). CONCLUSIONS: The visceral adiposity index can be a predictor of incident NAFLD.
Assuntos
Adiposidade , Gordura Intra-Abdominal , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Adulto , Alanina Transaminase/sangue , Consumo de Bebidas Alcoólicas , Glicemia/análise , Pressão Sanguínea , Índice de Massa Corporal , HDL-Colesterol/sangue , Intervalos de Confiança , Exercício Físico , Jejum/sangue , Fígado Gorduroso/diagnóstico por imagem , Feminino , Humanos , Incidência , Estudos Longitudinais , Masculino , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores Sexuais , Fumar , Triglicerídeos/sangue , Ultrassonografia , Circunferência da CinturaRESUMO
Nonalcoholic fatty liver disease (NAFLD) is associated with testosterone deficiency. However, NAFLD patients generally do not respond to treatment with testosterone alone. We investigated the innate immune mechanisms underlying the effects of treatment with testosterone alone, estrogen alone, or combined testosterone and estrogen on high-fat diet (HFD)-induced NAFLD due to testosterone deficiency. Orchiectomized (OCX) male Rag2-/- mice were used as a model of testosterone deficiency. To assess NAFLD severity, NAFLD activity score (NAS) is adopted. Moreover, immunological change was analyzed by multicolor flow cytometry. Treatment with both testosterone and estrogen significantly decreased body weight to that of the sham mice/normal diet (ND). NAS and liver fibrosis in OCX-HFD mice were significantly deteriorated, and treatment with testosterone and estrogen improved same as sham-ND mice. HFD increased the ratio of both type 2 and 3 innate lymphoid cells (ILC2s and ILC3s) to CD45-positive cells in the liver. Treatment with testosterone alone decreased the ratio of ILC2 to CD45 but not the ILC3-to-CD45 ratio. Addition of estrogen to the treatment reduced the ratios of ILC2-to-CD45 and ILC3-to-CD45 to the same level observed in sham-HFD mice. Moreover, OCX-HFD mice had a decreased proportion of M2 macrophages compared with sham-ND mice. Treatment with testosterone alone did not restore the proportion of M2 macrophages; however, combination treatment with both estrogen and testosterone increased that to the same level as that in sham-HFD mice. Treatment with both testosterone and estrogen improves liver fibrosis and decreases ILC3 and increases M2 macrophage abundance in the liver.NEW & NOTEWORTHY The progression of nonalcoholic fatty liver disease (NAFLD) is associated with testosterone deficiency. NAFLD patients generally do not respond to treatment with testosterone alone. In animal studies, treatment with testosterone and estrogen reduced the ratios of ILC2:CD45 and ILC3:CD45 and increased M2 macrophages in liver. Our study suggests, based on our immunological data, that a combination of estrogen and testosterone may be clinically relevant for the treatment of NAFLD in patients with male menopause.
Assuntos
Estradiol/farmacologia , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Testosterona/farmacologia , Aminoácidos , Animais , Carcinoma Hepatocelular , Linhagem Celular Tumoral , Cromo , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Cadeia alfa 1 do Colágeno Tipo I , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Dieta Hiperlipídica/efeitos adversos , Regulação para Baixo , Estradiol/administração & dosagem , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Insulina , Cirrose Hepática , Neoplasias Hepáticas , Masculino , Camundongos , Camundongos Knockout , Ácidos Nicotínicos , Hepatopatia Gordurosa não Alcoólica/patologia , Orquiectomia , Células RAW 264.7 , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores CCR2/genética , Receptores CCR2/metabolismo , Testosterona/administração & dosagem , Testosterona/deficiência , Fator de Crescimento Transformador beta1/genética , Fator de Crescimento Transformador beta1/metabolismoRESUMO
BACKGROUND AND AIMS: Visceral adiposity index (VAI), calculated with body mass index, high density lipoprotein-cholesterol, triglycerides and waist circumference, has been proposed as a marker of visceral fat accumulation and dysfunction in adipose tissue. METHODS: The impact of VAI on incident chronic kidney disease (CKD) in a historical cohort study of 15,159 (8,260 men and 6,899 women) participants was investigated. CKD was defined when estimated glomerular filtration rate was <60 mL/min/1.73 m2 or proteinuria (positive: ≥1+). We divided the participants into 2 groups according to sex and into quartiles according to VAI (Q1-4). We performed Cox proportional hazard models, adjusting for age, smoking status, exercise, alcohol consumption, systolic blood pressure, hemoglobin A1c, uric acid, and creatinine. RESULTS: During the median 3.3-year follow-up for men and 3.2-year follow-up for women, 1,078 participants (629 men and 449 women) developed CKD. The 4,000 days cumulative incidence rate of CKD for men and women were 3.7 and 3.9% in Q1, 5.2 and 5.9% in Q2, 6.5 and 7.0% in Q3, and 8.4 and 9.3% in Q4 respectively. Compared to Q1, the hazard ratios of incident CKD in Q2, Q3 and Q4 for men and women were 1.23 (95% CI 0.91-1.66, p = 0.184) and 1.30 (0.87-1.96, p = 0.203), 1.42 (1.06-1.90, p = 0.018) and 1.38 (0.94-2.05, p = 0.105), and 1.51 (1.12-2.02, p = 0.006) and 1.65 (1.12-2.46, p = 0.013) respectively. Additionally, the area under the curve of VAI for incidence of CKD was superior to that of VAI in men (0.595 vs. 0.552, p < 0.001) and equal to in women (0.597 vs. 0.591, p = 0.708). CONCLUSIONS: The VAI can be a predictor of incident CKD.
Assuntos
Gordura Intra-Abdominal/fisiopatologia , Obesidade Abdominal/complicações , Insuficiência Renal Crônica/etiologia , Adulto , Estudos de Coortes , Feminino , Humanos , Estudos Longitudinais , Masculino , Obesidade Abdominal/patologia , Insuficiência Renal Crônica/patologiaRESUMO
We have previously reported that the creatinine (Cre) to cystatin C (CysC) ratio is associated with height-adjusted skeletal muscle mass index (SMI). However, weight-adjusted SMI is reported to be a more useful marker of insulin sensitivity than height-adjusted SMI. Thus, we hypothesized that the creatinine to (cystatin C × body weight [BW]) relationship (Cre/[CysC × BW]) might be associated with weight-adjusted SMI. In this cross-sectional study of 169 males and 132 females, a body composition analyzer was used and the weight-adjusted SMI was calculated as (absolute muscle mass [kg]/BW [kg]) × 100. The cut-off of low muscle mass was defined as weight-adjusted SMI <37.0% for males and <28.0% for females. The Cre/(CysC × BW) was correlated with weight-adjusted SMI in both males (r = 0.484, p < 0.001) and females (r = 0.538, p < 0.001). In addition, Cre/(CysC × BW) was associated with weight-adjusted SMI in both males (standardized ß = 0.493, p < 0.001) and females (standardized ß = 0.570, p < 0.001) after adjusting for covariates. According to the receiver operator characteristic (ROC) curve analysis, the optimal cut-off point of Cre/(CysC × BW) for low muscle mass was 0.0145 (area under the ROC curve [AUC] 0.756 [95% confidence interval {95% CI} 0.644-0.842], sensitivity = 0.96, specificity = 0.47, p < 0.001) in males and 0.0090 (AUC 0.976 [95% CI 0.894-0.995], sensitivity = 1.00, specificity = 0.93, p < 0.001) in females. There is a correlation between Cre/(CysC × BW) and weight-adjusted SMI. The Cre/(CysC × BW) could be a practical screening marker for low muscle mass.
Assuntos
Peso Corporal/fisiologia , Creatinina/sangue , Cistatina C/sangue , Músculo Esquelético/anatomia & histologia , Sarcopenia/diagnóstico , Idoso , Composição Corporal/fisiologia , Índice de Massa Corporal , Estudos Transversais , Feminino , Humanos , Resistência à Insulina/fisiologia , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Tamanho do Órgão , Valor Preditivo dos Testes , Estudos Retrospectivos , Sarcopenia/sangue , Sarcopenia/patologiaRESUMO
OBJECTIVE: Reduction of muscle mass and strength is an important treatment target for patients with type 2 diabetes. Recent studies have reported that high-intensity resistance training improves physical function; however, all patients found it difficult to perform high-intensity resistance training. Radio calisthenics, considered as therapeutic exercises to promote health in Japan, are simple exercises that can be performed regardless of age and help move the muscles and joints of the whole body effectively according to the rhythm of radio. We investigated the efficacy of radio calisthenics for muscle mass in patients with type 2 diabetes in this retrospective cohort study. RESEARCH DESIGN AND METHODS: A total of 42 hospitalized patients with type 2 diabetes were recruited. The skeletal muscle mass index (SMI, kg/m2) was calculated as appendicular muscle mass (kg) divided by height squared (m2). We defined the change of SMI as the difference of SMI between the beginning and end of hospitalization. RESULTS: Among 42 patients, 15 (11 men and 4 women) performed radio calisthenics. Body weights of both radio calisthenics exercisers and non-exercisers decreased during hospitalization. The change of SMI was significantly lesser in radio calisthenics exercisers than in non-exercisers (7.1±1.4 to 7.1±1.3, -0.01±0.09 vs 6.8±1.1 to 6.5±1.2, -0.27±0.06 kg/m2, p=0.016). The proportion of decreased SMI was 85.2% (23/27 patients) in non-radio calisthenics exercisers, whereas that in radio calisthenics exercisers was 46.7% (7/15 patients). CONCLUSIONS: Radio calisthenics prevent the reduction of skeletal muscle mass. Thus, radio calisthenics can be considered effective for patients with type 2 diabetes.