Associations of ALT/AST, a marker of hepatosteatosis, with pulse rate in young women and with blood pressure in middle-aged women independently of abdominal fat accumulation and insulin resistance.

We examined whether alanine aminotransferase/aspartate aminotransferase (ALT/AST), a marker of hepatosteatosis, may be associated with a wider constellation of variables related to metabolic syndrome in Japanese women. Body fat and distribution, and metabolic syndrome-related variables were measured in 311 young and 148 middle-aged women. We had Pearson's correlation analysis and then stepwise multivariate linear regression analyses. In both middle-aged and young women, ALT/AST was associated with homeostasis model assessment insulin resistance (HOMA-IR), trunk/leg fat ratio and pulse rate. In middle-aged women but not in young women, ALT/AST was associated with waist circumference, fasting glucose, triglyceride, HDL cholesterol (inversely), systolic, diastolic and mean blood pressure (BP). Further, in middle-aged women only, the ratio was associated with BMI, percentage body fat, apolipoprotein B and plasminogen activator inhibitor-1. Among these variables, pulse rate in young women and systolic BP in middle-aged women were associated with ALT/AST independently of trunk/leg fat ratio, a sophisticated measures of abdominal fat accumulation,　HOMA-IR, fasting glucose, triglyceride and HDL cholesterol. In conclusion, ALT/AST was associated with pulse rate in young women and with systolic BP in middle-aged women independently of abdominal fat accumulation and insulin resistance. It is noted that their waist circumference averaged < 80 cm and ALT < 30 U/L, suggesting minimum accumulation of abdominal and hepatic fat, respectively, key drivers of insulin resistance and metabolic syndrome. Supplementary Information: The online version contains supplementary material available at 10.1007/s13340-023-00689-z.

Higher childhood weight gain, lower skeletal muscle mass, and higher cereal consumption in normal-weight Japanese women with high-percentage trunk fat: a subanalysis study.

Normal-weight but high-percentage trunk fat phenotype was characterized in a setting where adiposity is not associated with educational and socioeconomic status. Body size trajectory since birth, current body composition measured using whole-body dual-energy X-ray absorptiometry, cardiometabolic traits, serum adipokines, and dietary intake were measured cross-sectionally in 251 normal weight Japanese female university students whose fasting triglyceride and homeostasis model assessment-insulin resistance (HOMA-IR) averaged 56 mg/dL and 1.2, respectively. They were grouped according to tertile of percentage trunk fat. Although HOMA-IR did not differ among three groups, high-percentage trunk fat was associated with higher triglyceride and apolipoprotein B, and lower HDL cholesterol and apolipoprotein A1. In multivariate logistic regression analyses, weight-adjusted skeletal muscle mass (OR: 0.13, 95% CI: 0.04-0.38, p < 0.001), weight gain from birth to age 12 years (OR: 1.214、95% CI: 1.008-1.463、p = 0.04), and cereal consumption (OR:1.008, 95% CI: 1.000-1.016, p = 0.04) were associated with high-percentage trunk fat independent of birthweight, HOMA-IR, adipose tissue-insulin resistance index (the product of fasting insulin and free fatty acid), triglyceride, HDL cholesterol, apolipoprotein A1 and B, leptin, adiponectin, blood pressure, and high-sensitivity C-reactive protein. Early childhood growth, lower skeletal muscle mass, and higher cereal consumption may be associated with normal-weight but high-percentage trunk fat phenotype in Japanese female university students in this subanalysis study. Atherogenic profile of lipids and apolipoproteins may be directly related to abdominal fat accumulation.

Associations of Alanine Aminotransferase/Aspartate Aminotransferase, a Marker of Hepatosteatosis, with Adipose Tissue Insulin Resistance Index and Leptin/Adiponectin Ratio in Japanese Women.

Objective: We assessed whether alanine aminotransferase/aspartate aminotransferase (ALT/AST), a marker of hepatic steatosis, may be associated with adipose tissue dysfunction more closely than hepatic and muscle insulin resistance (IR). Methods: Associations with adipose tissue IR index (AT-IR) calculated as a product of fasting insulin and free fatty acids, leptin/adiponectin ratio, a proxy of adipocyte dysfunction, homeostasis model assessment IR (HOMA-IR), hepatic and muscle IR inferred from plasma insulin kinetics during a 75 grams oral glucose tolerance test (OGTT) were studied in nondiabetic 307 young and 148 middle-aged Japanese women, whose body mass index averaged 20 and 22 kilograms/m2, respectively. Results: On multivariate linear regression analysis in young women, ALT/AST was associated with trunk/leg fat ratio (standardized ß = 0.202, P = 0.007), a marker of abdominal fat accumulation, and AT-IR (standardized ß = 0.185, P = 0.003) independently of HOMA-IR and Matsuda index (R2 = 0.07). In middle-aged women, leptin/adiponectin ratio (standardized ß = 0.446, P < 0.001) and AT-IR (standardized ß = 0.292, P = 0.009) emerged as determinants of ALT/AST independently of trunk/leg fat ratio, OGTT-derived hepatic IR, leptin, and adiponectin (R2 = 0.34). Conclusions: ALT/AST was associated with AT-IR and adipocyte dysfunction more closely than hepatic and muscle IR even in nondiabetic lean Japanese women.

Associations of alanine aminotransferase/aspartate aminotransferase with insulin resistance and ß-cell function in women.

We tested whether alanine aminotransferase/aspartate aminotransferase (ALT/AST), a marker of hepatosteatosis, associates with insulin resistance, ß-cell function and postglucose glycemia. We studied 311 young and 148 middle-aged Japanese women, whose BMI averaged < 23.0 kg/m2. Insulinogenic index and Matsuda index were evaluated in 110 young and 65 middle-aged women. In two groups of women, ALT/AST was associated positively with homeostasis model assessment insulin resistance (HOMA-IR) and inversely with Matsuda index. In middle-aged women only, the ratio was also associated positively with fasting and postload glycemia and HbA1c. The ratio showed negative association with disposition index (a product of insulinogenic index and Matsuda index). On multivariate linear regression analysis, HOMA-IR emerged as a single determinant of ALT/AST in young and middle-aged women (standardized ß: 0.209, p = 0.003 and 0.372, p = 0.002, respectively). ALT/AST was associated with insulin resistance and ß-cell function even in non-obese Japanese women, suggesting a pathophysiologic basis in its prediction of diabetic risk.

Association between serum leptin concentrations and homeostasis model assessment-insulin resistance of 2.5 and higher in normal weight Japanese women.

Normal weight insulin resistant phenotype was characterized in 251 Japanese female university students using homeostasis model assessment-insulin resistance. Birth weight, body composition at age 20, cardiometabolic traits and dietary intake were compared cross-sectionally between insulin sensitive (< 1.6, n = 194) and insulin resistant (2.5 and higher, n = 16) women. BMI averaged < 21 kg/m2 and waist < 72 cm and did not differ between two groups. The percentage of macrosomia and serum absolute and fat-mass corrected leptin concentrations were higher in insulin resistant women although there was no difference in birth weight, fat mass index, trunk/leg fat ratio and serum adiponectin. In addition, resting pulse rate, serum concentrations of free fatty acids, triglycerides and remnant-like particle cholesterol were higher in insulin resistant women although HDL cholesterol and blood pressure did not differ. In multivariate logistic regression analyses, serum leptin (odds ratio:1.68, 95% confidential interval:1.08-2.63, p = 0.02) was associated with normal weight insulin resistance independently of macrosomia, free fatty acids, triglycerides, remnant-like particle cholesterol and resting pulse rate. In conclusion, normal weight IR phenotype may be associated with increased plasma leptin concentrations and leptin to fat mass ratio in young Japanese women, suggesting higher leptin production by body fat unit.

Weight trajectories since birth, current body composition and metabolic traits in young, normal-weight Japanese women with high percentage body fat.

INTRODUCTION: We tested whether normal-weight obesity might be associated with weight trajectories, body composition and metabolic traits. RESEARCH DESIGN AND METHODS: Body size trajectory since birth, body composition at age 20 years and metabolic traits were compared cross-sectionally among normal-weight Japanese women with low (<25.0%, n=67), normal (25.0-34.9%, n=160) and high (≥35.0 %, n=24) percentage body fat. Multivariate logistic regression analyses were used to identify most important determinants of normal-weight obesity (high percentage body fat). RESULTS: Fasting glucose averaged <84 mg/dL, homeostasis model assessment-insulin resistance <1.4 and triglyceride <70 mg/dL and did not differ among three groups. However, waist and trunk/leg fat ratio were higher, and weight-adjusted skeletal muscle mass was lower in normal-weight obesity. Serum and LDL cholesterol, apolipoprotein B (ApoB) and high-sensitivity C reactive protein were higher, and apolipoprotein A1 was lower in normal-weight obesity compared with the other two groups, whereas HDL cholesterol did not differ. Weight gain from birth to age 12 years was higher in normal-weight obesity. In multivariate logistic regression analyses, weight gain until 12 years (OR: 1.17,95% CI 1.02 to 1.34, p=0.02), ApoB (OR: 1.15, 95% CI 1.06 to 1.24, p<0.001) and weight-adjusted skeletal muscle mass (OR: 0.22, 95% CI 0.10 to 0.49, p<0.001) were associated with normal-weight obesity independently of trunk/leg fat ratio, high-sensitivity C reactive protein and apolipoprotein A1. CONCLUSIONS: Normal-weight obesity may be associated with early childhood growth, lower skeletal muscle mass and higher serum ApoB in young Japanese women through mechanisms unrelated to abdominal adiposity, inflammation and insulin resistance.

Higher fasting glucose, triglycerides, resting pulse rate and high-sensitivity C reactive protein in adipose insulin-resistant but normal weight young Japanese women.

INTRODUCTION: Adipose insulin-resistant but normal weight phenotype has not been reported and hence was characterized in young Japanese women. RESEARCH DESIGN AND METHODS: Body composition, a broad range of cardiometabolic health and dietary intake were cross-sectionally measured in 166 normal weight young Japanese women. They were grouped into tertile of adipose tissue-insulin resistance (AT-IR) index (fasting insulin×free fatty acids) and analyzed by analysis of variance and then Bonferroni's multiple comparison procedure. RESULTS: Body mass index averaged <21 kg/m2 and waist <72 cm, and did not differ among three groups of women. Fasting glucose and triglycerides and homeostasis model assessment-insulin resistance were higher in the highest compared with the median and lowest AT-IR tertile. However, there was no difference in fat mass and distribution, high-density lipoprotein cholesterol and blood pressure. In addition, high-sensitivity C reactive protein (hsCRP) and resting pulse rate were higher as well. In multivariate logistic regression analyses, fasting glucose (OR: 1.10, 95% CI: 1.02 to 1.18, p=0.012), fasting triglycerides (OR: 1.04, 95% CI: 1.02 to 1.06, p<0.001), resting pulse rate (OR: 1.07, 95% CI: 1.03 to 1.11, p<0.001) and hsCRP (OR: 2.30, 95% CI: 1.01 to 5.2, p=0.04) were associated with the high AT-IR tertile. CONCLUSIONS: Adipose insulin-resistant but normal weight phenotype may be associated with increased sympathetic nervous system and low-grade systemic inflammation in addition to glucose and lipid dysmetabolism through mechanisms unrelated to adiposity in young Japanese women.