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The age- and sex-related differences on the impacts of body composition on diabetes mellitus (DM) remain uncertain.
The fourth and fifth Korea National Health and Nutrition Examination Survey included 15,586 subjects over 30 years of age who completed dual-energy X-ray absorptiometry. We conducted a cross-sectional study to investigate whether muscle mass index (MMI), defined as appendicular skeletal muscle divided by body mass index (BMI), and fat mass index (FMI), defined as trunk fat mass divided by BMI, were differently associated with DM according to age and sex.
In multivariate logistic regression, the risk for DM significantly increased across quartiles of FMI in men aged ≥70. Meanwhile, MMI showed a protective association with DM in men of the same age. The odds ratios (ORs) for the highest quartile versus the lowest quartile of FMI and MMI were 3.116 (95% confidence interval [CI], 1.405 to 6.914) and 0.295 (95% CI, 0.157 to 0.554), respectively. In women, the ORs of DM was significantly different across FMI quartiles in those over age 50. The highest quartile of FMI exhibited increased ORs of DM in subjects aged 50 to 69 (OR, 1.891; 95% CI, 1.229 to 2.908) and ≥70 (OR, 2.275; 95% CI, 1.103 to 4.69) compared to lowest quartile. However, MMI was not significantly associated with DM in women of all age groups.
Both FMI and MMI were independent risk factors for DM in men aged 70 years or more. In women over 50 years, FMI was independently associated with DM. There was no significant association between MMI and DM in women.
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Skeletal muscle is the largest tissue in the human body, and it plays a major role in exerting force and maintaining metabolism homeostasis. The role of muscle transcription factors in the regulation of metabolism is not fully understood. MondoA is a glucose-sensing transcription factor that is highly expressed in skeletal muscle. Previous studies suggest that MondoA can influence systemic metabolism homeostasis. However, the function of MondoA in the skeletal muscle remains unclear.
We generated muscle-specific MondoA knockout (MAKO) mice and analyzed the skeletal muscle morphology and glycogen content. Along with skeletal muscle from MAKO mice, C2C12 myocytes transfected with small interfering RNA against MondoA were also used to investigate the role and potential mechanism of MondoA in the development and glycogen metabolism of skeletal muscle.
MAKO caused muscle fiber atrophy, reduced the proportion of type II fibers compared to type I fibers, and increased the muscle glycogen level. MondoA knockdown inhibited myoblast proliferation, migration, and differentiation by inhibiting the phosphatase and tensin homolog (PTEN)/phosphoinositide 3-kinase (PI3K)/Akt pathway. Further mechanistic experiments revealed that the increased muscle glycogen in MAKO mice was caused by thioredoxin-interacting protein (TXNIP) downregulation, which led to upregulation of glucose transporter 4 (GLUT4), potentially increasing glucose uptake.
MondoA appears to mediate mouse myofiber development, and MondoA decreases the muscle glycogen level. The findings indicate the potential function of MondoA in skeletal muscle, linking the glucose-related transcription factor to myogenesis and skeletal myofiber glycogen metabolism.
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To elucidate longitudinal changes of complex body composition phenotypes and their association with incident type 2 diabetes mellitus.
A total of 17,280 (mean age, 48.1±8.2 years) Korean adults who underwent medical check-ups were included. The mean follow-up duration was 5.5±0.5 years. Body compositions were assessed using a bioelectrical impedance analysis. Four body composition phenotypes were defined using the median of appendicular skeletal muscle mass (ASM) index and fat mass index: low muscle/low fat (LM/LF); high muscle (HM)/LF; LM/high fat (HF); and HM/HF groups.
Of the individuals in the LM/LF or HM/HF groups, over 60% remained in the same group, and over 30% were moved to the LM/HF group. Most of the LM/HF group remained in this group. In the baseline HM/LF group, approximately 30% stayed in the group, and the remaining individuals transitioned to the three other groups in similar proportions. Incident diabetes was significantly lower in participants who remained in the HM/LF group than those who transitioned to the LM/LF or LM/HF group from the baseline HM/LF group in men. ASM index was significantly associated with a decreased risk for incident diabetes in men regardless of obesity status (adjusted odds ratio [OR], 0.71 per kg/m2; 95% confidence interval [CI], 0.52 to 0.97 in non-obese) (adjusted OR, 0.87; 95% CI, 0.77 to 0.98 in obese) after adjusting for other strong risk factors (e.g., baseline glycosylated hemoglobin and homeostasis model assessment of insulin resistance).
Maintenance of ASM may be protective against the development of type 2 diabetes mellitus in men, regardless of obesity status.
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Sarcopenic obesity (SO) is a serious public health concern, few studies have examined the clinical implications of SO in newly-diagnosed type 2 diabetes mellitus (T2DM) patients. We evaluated the prevalence of the newly diagnosed, drug-naïve T2DM patients with low muscle mass with abdominal obesity and its association with insulin resistance and other diabetic complications.
We classified 233 drug-naïve T2DM subjects into four groups according to abdominal obesity (waist circumference ≥90 cm in men and ≥85 cm in women) and low muscle mass status (appendicular skeletal muscle <7.0 kg/m2 for men and <5.4 kg/m2 for women).
The proportion of the subjects with low muscle mass and abdominal obesity among the newly diagnosed, drug-naïve T2DM patients was 8.2%. Homeostasis model assessment of insulin resistance (HOMA-IR) increased linearly according to body composition group from normal to abdominal obesity to both low muscle mass and abdominal obesity. The multiple logistic regression analysis indicated that subjects with low muscle mass and abdominal obesity (odds ratio [OR], 9.39; 95% confidence interval [CI], 2.41 to 36.56) showed a higher risk for insulin resistance, defined as HOMA-IR ≥3, than those with abdominal obesity (OR, 5.36; 95% CI, 2.46 to 11.69), even after adjusting for other covariates. However, there were no differences in lipid profiles, microalbuminuria, or various surrogate markers for atherosclerosis among the four groups.
Subjects with both low muscle mass and abdominal obesity had a higher risk of insulin resistance than those with low muscle mass or abdominal obesity only.
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Skeletal muscle plays a major role in glucose metabolism. We investigated the association between thigh muscle mass, insulin resistance, and incident type 2 diabetes mellitus (T2DM) risk. In addition, we examined the role of body mass index (BMI) as a potential effect modifier in this association.
This prospective study included 399 Japanese Americans without diabetes (mean age 51.6 years) who at baseline had an estimation of thigh muscle mass by computed tomography and at baseline and after 10 years of follow-up a 75-g oral glucose tolerance test and determination of homeostasis model assessment of insulin resistance (HOMA-IR). We fit regression models to examine the association between thigh muscle area and incidence of T2DM and change in HOMA-IR, both measured over 10 years.
Thigh muscle area was inversely associated with future HOMA-IR after adjustment for age, sex, BMI, HOMA-IR, fasting plasma glucose, total abdominal fat area, and thigh subcutaneous fat area at baseline (
Thigh muscle mass area was inversely associated with future insulin resistance. Greater thigh muscle area predicts a lower risk of incident T2DM for leaner Japanese Americans.
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The study aimed to investigate the influence of hyperglycemia on muscle quality in older men with type 2 diabetes.
This was a subsidiary study of the Korean Longitudinal Study of Health and Aging. Among 326 older men consenting to tests of body composition and muscle strength, 269 men were ultimately analyzed after the exclusion because of stroke (
The muscle mass, strength, and quality in patients with type 2 diabetes did not differ significantly from controls. However, when patients with diabetes were subdivided according to their glycemic control status, patients with a glycosylated hemoglobin (HbA1c) level of ≥8.5% showed significantly decreased leg muscle quality by multivariate analysis (odds ratio, 4.510;
Poor glycemic control in these older patients with diabetes was associated with significant risk of decreased muscle quality and performance status. Glycemic control with an HbA1c of <8.5% might be needed to reduce the risk of adverse skeletal and functional outcomes in this population.
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Visceral adiposity is related to insulin resistance. Skeletal muscle plays a central role in insulin-mediated glucose disposal; however, little is known about the association between muscle mass and metabolic syndrome (MS). This study is to clarify the clinical role of skeletal muscle mass in development of MS.
A total of 1,042 subjects were enrolled. Subjects with prior MS and chronic diseases were excluded. After 24 months, development of MS was assessed using NCEP-ATP III criteria. Skeletal muscle mass (SMM; kg), body fat mass (BFM; kg), and visceral fat area (VFA; cm2) were obtained from bioelectrical analysis. Then, the following values were calculated as follows: percent of SMM (SMM%; %): SMM (kg)/weight (kg), skeletal muscle index (SMI; kg/m2): SMM (kg)/height (m2), skeletal muscle to body fat ratio (MFR): SMM (kg)/BFM (kg), and skeletal muscle to visceral fat ratio (SVR; kg/cm2): SMM (kg)/VFA (cm2).
Among 838 subjects, 88 (10.5%) were newly diagnosed with MS. Development of MS increased according to increasing quintiles of BMI, SMM, VFA, and SMI, but was negatively associated with SMM%, MFR, and SVR. VFA was positively associated with high waist circumference (WC), high blood pressure (BP), dysglycemia, and high triglyceride (TG). In contrast, MFR was negatively associated with high WC, high BP, dysglycemia, and high TG. SVR was negatively associated with all components of MS.
Relative SMM ratio to body composition, rather than absolute mass, may play a critical role in development of MS and could be used as a strong predictor.
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Nonalcoholic fatty liver disease (NAFLD) is closely correlated with abnormal accumulation of visceral fat, but the role of skeletal muscle remains unclear. The aim of this study was to elucidate the role of skeletal muscle in development of NAFLD.
Among 11,116 subjects (6,242 males), we examined the effects of skeletal muscle mass and visceral fat area (VFA, by bioelectric impedance analysis) on NAFLD using by the fatty liver index (FLI).
Of the total subjects (9,565 total, 5,293 males) included, 1,848 were classified as having NALFD (FLI ≥60). Body mass index, lipid profile, fasting plasma glucose, hemoglobin A1c, prevalence of type 2 diabetes (DM), hypertension (HTN), and metabolic syndrome were higher in males than females, but FLI showed no significant difference. The low FLI group showed the lowest VFA and highest skeletal muscle mass of all the groups. Skeletal muscle to visceral fat ratio (SVR) and skeletal muscle index had inverse correlations with FLI, when adjusted for age and gender. In multivariate regression analysis, SVR was negatively associated with FLI. Among SVR quartiles, the highest quartile showed very low risk of NAFLD when adjusted for age, gender, lipid profile, DM, HTN, and high sensitivity C-reactive protein from the lowest quartiles (odds ratio, 0.037; 95% confidence interval, 0.029 to 0.049).
Skeletal muscle mass was inversely associated with visceral fat area, and higher skeletal muscle mass may have a beneficial effect in preventing NAFLD. These results suggest that further studies are needed to ameliorate or slow the progression of sarcopenia.
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Inflammation plays a role in the response to metabolic stress in type 2 diabetes. However, the effects of rosiglitazone on inflammation of skeletal muscle have not been fully examined in type 2 diabetes.
We investigated the effects of the insulin-sensitizing anti-diabetic agent, rosiglitazone, on the progression of skeletal muscle inflammation in Otsuka Long-Evans Tokushima Fatty (OLETF) type 2 diabetic rats. We examined the expression of serologic markers (serum glucose, insulin and free fatty acid) and inflammatory cytokines (tumor-necrosis factor-α, interleukin [IL]-1β and IL-6) in OLETF rats from early to advanced diabetic stage (from 28 to 40 weeks of age).
Serum glucose and insulin concentrations were significantly decreased in rosiglitazone-treated OLETF rats compared to untreated OLETF rats. Rosiglitazone treatment significantly decreased the concentrations of serum inflammatory cytokines from 28 to 40 weeks of age. The mRNA expression of various cytokines in skeletal muscle was reduced in rosiglitazone-treated OLETF rats compared with untreated OLETF rats. Furthermore, rosiglitazone treatment resulted in the downregulation of ERK1/2 phosphorylation and NF-κB expression in the skeletal muscle of OLETF rats.
These results suggest that rosiglitazone may improve insulin sensitivity with its anti-inflammatory effects on skeletal muscle.
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