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.

Influence of the nutritional status on facial morphology in young Japanese women.

Evidence regarding the possible influence of nutritional status on the facial morphology has thus far been insufficient. We examined whether or not the physical body compositions and dietary behaviors were correlated with any morphological characteristics of the face. One hundred and fifteen young Japanese women participated. Variables representing the dietary behaviors were extracted from self-reported survey data, and corresponding three-dimensional (3D) facial images and body compositions were examined. Multivariate analyses identified significant relationships between the nutritional status and facial topography (p < 0.05). The clustering method revealed the existence of three dietary condition patterns ("balanced diet", "high-calorie-diet" with obesity tendency, and "imbalanced low-calorie-diet" with sarcopenic obesity tendency). Among these three patterns, a round face (increased facial width; analysis of variance [ANOVA], p < 0.05) was observed in the high-calorie-diet pattern, while the imbalanced low-calorie-diet pattern showed a more masculine face (increased face height, decreased eye height, increased non-allometric sexual shape differences; ANOVA, p < 0.05), thus suggesting the possibility of sex-hormonal influences. In summary, the body composition and dietary behaviors were found to influence the facial morphology, and potential biological influences were discussed.

Reduced gluteofemoral (subcutaneous) fat mass in young Japanese women with family history of type 2 diabetes: an exploratory analysis.

Limited expandability of subcutaneous adipose tissue may be characteristics of first-degree relatives of type 2 diabetes. We tested the hypothesis that family history of type 2 diabetes (FHD) may be associated with reduced peripheral fat mass. Body composition and metabolic variables were compared between 18 and 111 Japanese female collegiate athletes, and between 55 and 148 nonathletes with positive (FHD +) and negative FHD (FHD-), respectively. We had multivariate logistic regression analyses for FHD + as dependent variable in a total population.BMI averaged < 21 kg/m2 and did not differ between FHD + and FHD- nonathletes. Despite comparable BMI, body fat percentage and serum leptin were lower in FHD + nonathletes. This was due to lower arm and gluteofemoral fat percentage (both p = 0.02) whereas the difference in trunk fat percentage was not significant (p = 0.08). These differences were not found between two groups of athletes. FHD + women had lower HDL cholesterol despite lower BMI in a total population. Fasting insulin, serum adiponectin and high-sensitivity C-reactive protein did not differ between FHD + and FHD- athletes or nonathletes. Multivariate logistic regression analyses revealed independent associations of FHD + with BMI (odds ratio, 0.869; 95% confidential interval, 0.768-0.984; p = 0.02) and HDL cholesterol (odds ratio, 0.977; 95% confidential interval, 0.957-0.997, p = 0.02). In conclusion, FHD may be associated with reduced subcutaneous fat mass in young Japanese women, suggesting impaired adipose tissue expandability.

Birth weight was associated positively with gluteofemoral fat mass and inversely with 2-h postglucose insulin concentrations, a marker of insulin resistance, in young normal-weight Japanese women.

Introduction: We tested whether birth weight might be associated with gluteofemoral fat mass and insulin sensitivity later in life. Materials and methods: Body size trajectory since birth, body composition at age 20, and markers of insulin resistance were measured in 316 Japanese women. A subset of 148 women underwent a 75 g oral glucose tolerance test. Multiple linear regression analyses were used to identify most important determinants of birth weight. Results: Birth weight was correlated positively with height and weight at age 12, 15, and 20 years (all p < 0.001 except for weight at 12 years, p = 0.03). Although it showed no correlation with BMI at age 12 and 15, it was correlated positively with current BMI (p = 0.006). It showed positive correlations with lean mass in arms, legs, trunk, and the whole body at age 20 (all p < 0.001). Additionally, it was correlated positively with leg (gluteofemoral) fat mass (p = 0.007), although there was no correlation with total body and trunk fat mass. Furthermore, weight at birth showed inverse correlations with 2-h postglucose insulin concentrations (p = 0.008) whereas it was not correlated with fasting insulin and homeostasis model assessment-insulin resistance. In a multiple regression analysis, which included anthropometric and biochemical variables as independent variables, appendicular muscle mass (standardized ß 0.394, p < 0.001) emerged as a single determinant of birth weight (R 2 = 0.15). In a model which included gluteofemoral fat mass and 2-h postglucose insulin, birth weight was associated with gluteofemoral fat mass (standardized ß 0.240, p = 0.003) and 2-h postglucose insulin concentrations (standardized ß - 0.217, p = 0.007) (R 2 = 0.09). Conclusions: Birth weight was associated positively with gluteofemoral fat mass and inversely with 2-h postglucose insulin concentrations, a marker of insulin resistance.

Weight Trajectory Since Birth, Current Body Composition, Dietary Intake, and Glucose Tolerance in Young Underweight Japanese Women.

Introduction: We studied weight trajectory since birth and dietary intake in Japanese female students majoring in nutrition sciences. Materials and Methods: Birth weight, adolescent height and weight, current body composition by whole-body dual-energy X-ray absorptiometry, dietary intake, glucose tolerance, lipid profile, and adipokines were cross-sectionally compared between young underweight (body mass index [BMI] <18.5) and normal-weight (BMI ≥18.5 and <25.0) women with overweight (BMI ≥25.0) women as an internal reference. Results: Serum adiponectin (leptin) was the highest (lowest) in 42 underweight women, intermediate levels in 251 normal-weight women, and the lowest (highest) levels in 14 overweight women. Compared with normal-weight women, underweight women had lower weight at birth, at age 12, 15, and 20 years, but comparable height, and hence lower BMI at three time points. Underweight women had higher gluteofemoral fat adjusted for total body fat and weight-adjusted skeletal muscle mass, although absolute and height-adjusted fat mass and skeletal muscle mass were lower. Glucose tolerance assessed by oral glucose testing, serum triglycerides, and high-density lipoprotein cholesterol did not differ between the two groups. Daily intake expressed per kg of body mass of energy and protein was the highest in underweight women, intermediate levels in normal-weight women, and the lowest levels in overweight women. Conclusions: Some young Japanese women are underweight not because of a strong drive for thinness, but because they were born lighter and remained lean until young adults. Underweight was associated with higher gluteofemoral fat adjusted for total body fat and relative skeletal muscle mass.

Serum Orosomucoid Is Associated with Serum Adiponectin, Adipose Tissue Insulin Resistance Index, and a Family History of Type 2 Diabetes in Young Normal Weight Japanese Women.

INTRODUCTION: Adipose tissue (AT) expandability may be facilitated by adiponectin and suppressed by orosomucoid, and reduced AT expandability may be associated with first-degree relatives of type 2 diabetes. We tested the hypothesis that orosomucoid may be associated not only with adiponectin and adipose tissue insulin resistance but also with a family history of type 2 diabetes (FHD). Research Design and Methods. Anthropometric and metabolic variables, adipokines, and measures of inflammatory and insulin resistance were cross-sectionally investigated in 153 young normal weight Japanese women. Stepwise multivariate linear regression analyses were used to identify the most important determinants of orosomucoid. RESULTS: Orosomucoid was higher in women with positive (n = 57) compared to women with negative FHD and was associated positively with FHD (both p = 0.01). Orosomucoid also showed positive associations with fasting glucose (p < 0.001), free fatty acids (p = 0.001), and HbA1c (p = 0.007), whereas there was no association with fasting insulin and serum lipids. In addition, orosomucoid was associated inversely with adiponectin (p = 0.02) and positively with adipose tissue-insulin resistance index (AT-IR, the product of fasting insulin and free fatty acids; p = 0.001) but not with homeostasis model assessment-insulin resistance, leptin, and high-sensitivity C-reactive protein. In multivariate analyses, AT-IR (standardized ß, 0.22; p = 0.003), serum adiponectin (standardized ß, -0.163; p = 0.032), FHD+ (standardized ß, 0.178; p = 0.029), and HbA1c (standardized ß, 0.213; p = 0.005) emerged as independent determinants of orosomucoid and explained 15.2% of its variability. CONCLUSIONS: These results are the first to demonstrate that orosomucoid is associated not only with adipose tissue-insulin resistance and adiponectin but also with FHD.

Associations of Infant Feeding with Body Composition and Cardiometabolic Health in Young Female University Students.

Background: We assessed the association of infant feeding with body composition and cardiometabolic health at 20 years in a setting where infant feeding is not associated with socioeconomic status. Materials and methods: Body size trajectory since birth, current body composition measured using whole-body dual-energy X-ray absorptiometry, and a broad range of cardiometabolic risk factors were compared cross-sectionally among young female university students who were ever breastfed (n = 158, 120 exclusively, and 38 mainly), mixed fed (n = 124), and formula fed (n = 15, 10 mainly, and 5 exclusively) Results: Compared with breastfed and mixed fed women, formula fed women had higher serum total and low-density lipoprotein (LDL) cholesterol although fat mass, fat distribution, fasting glucose, and insulin and high-density lipoprotein cholesterol did not differ. In addition, resting heart rates were higher in formula fed women compared with the other two groups of women although systolic and diastolic blood pressure did not differ. Further, formula fed women had higher adiponectin while serum leptin did not differ. There was no difference in birthweight, weight and height in childhood and adolescence, and glucose tolerance. On multivariate logistic regression analysis, formula feeding was associated with resting heart rates (odds ratio [OR]: 1.06, confidence interval [95% CI]; 1.01-1.12, p = 0.01) and adiponectin (OR: 1.3, 95% CI; 1.1-1.5, p < 0.001) independently of serum total and LDL cholesterol. Conclusions: Breastfeeding may be associated with favorable lipid profile and autonomic nervous function in young adults through mechanisms unrelated to adiposity, implicating potential long-term benefits of breastfeeding for cardiovascular health. Higher adiponectin in nonbreastfed women warrants further studies.

Association of family history of type 2 diabetes with blood pressure and resting heart rate in young normal weight Japanese women.

OBJECTIVE: We suggested association of family history of type 2 diabetes (FHD) with microvascular dysfunction, which may cause blood pressure (BP) elevations. We test whether FHD may be associated with higher BP. RESEARCH DESIGN AND METHODS: Resting BP, heart rates (in beats per minute: bpm), body composition and fasting concentrations of glucose, insulin, leptin and adiponectin were measured in 332 Japanese women aged 18-24 years. They were grouped according to BP category defined by the 2017 American College of Cardiology/American Heart Association Blood Pressure Guideline. RESULTS: BMI averaged < 22 kg/m2 and did not differ cross-sectionally between 73 with (FHD+) and 259 without FHD (FHD-). FHD+ had higher mean (81 ± 9 vs. 77 ± 7 mmHg, p < 0.001), systolic (111 ± 13 vs. 106 ± 10 mmHg, p = 0.003) and diastolic BP (65 ± 8 vs. 60 ± 7 mmHg, p < 0.001). Prevalence of elevated BP (11.0 vs. 6.2%), hypertension stage 1 (4.1 vs. 0.8%) and stage 2 (2.7 vs. 0.4%) was higher as well (p = 0.01). Endurance training in FHD+ abolished the differences in BP readings and BP prevalence. However, the mean resting heart rate in FHD+ athletes (61.2 bpm) was close to those in FHD+ (64.7 bpm) and FHD- nonathletes (64.6 bpm) and was higher than in FHD- athletes (56.5 bpm). Fat mass and distribution evaluated by dual-energy X-ray absorptiometry, markers of insulin resistance, and serum adipokines studied did not differ between the two groups. CONCLUSIONS: FHD was associated with higher BP and higher prevalence of elevated BP and hypertension, suggesting contribution of microvascular dysfunction in BP elevations in normal weight young Japanese women. FHD may be associated with reduced heart rate response to endurance training as well.

Elevated Blood Pressure (≥120/80 mmHg) Is Associated with Elevated Serum Plasminogen Activator Inhibitor-1, Low Birth Weight, and Family History of Diabetes in Young Normal Weight Japanese Women.

Objective: We examined whether elevated blood pressure (BP) (≥120/80 mmHg) was associated with several anthropometric, metabolic, and clinical variables, including the family history of type 2 diabetes (FHD) and low birth weight, in young normal weight Japanese women. Methods: BP, body composition, and fasting glucose, insulin, lipids, lipoproteins, apolipoproteins, and adipokines were measured in 332 young Japanese women. They received a questionnaire on birth weight and FHD. Results: The prevalence of low birth weight was 2.4% and that of positive FHD was 22.9%. Homeostasis model assessment-insulin resistance averaged <1.5 and did not differ cross-sectionally between 32 women with elevated BP and 300 women with normal BP although mean body mass index was higher in the former than in the latter (21.7 ± 2.9 kg/m2 vs. 20.8 ± 2.2 kg/m2, P = 0.02). Women with elevated BP had higher fat mass index (P = 0.02) and trunk fat percentage (P = 0.04). They had lower high-density lipoprotein (HDL) cholesterol and apolipoprotein A1 (both P = 0.01) while fasting triglycerides and apolipoprotein B did not differ. In addition, they had higher plasminogen activator inhibitor-1 (PAI-1) (P = 0.001). Furthermore, the prevalence of low birth weight (9.4% vs. 1.7%, P = 0.03) and positive FHD (40.6% vs. 20.0%, P = 0.01) was higher in women with elevated BP. Multivariable logistic regression analyses revealed that elevated BP was independently associated with PAI-1 [odds ratio (OR); 1.05, 95% confidence interval (CI): 1.02-1.08, P = 0.001], low birth weight (OR: 12.3, 95% CI: 2.3-67.3, P = 0.04), and FHD (OR: 3.0, 95% CI: 1.3-7.9, P = 0.01). Conclusion: Elevated BP was associated with positive FHD, low birth weight, and elevated serum PAI-1 in young normal weight Japanese women.

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.

Associations of serum transthyretin with triglyceride in non-obese elderly Japanese women independently of insulin resistance, HDL cholesterol, and adiponectin.

OBJECTIVE: Studies are limited on the association between serum transthyretin (TTR), a negative acute phase reactant, and triglyceride (TG). RESEARCH DESIGN AND METHODS: TG, TTR, and insulin resistance-related cardiometabolic variables were measured in 159 fasting and 185 nonfasting community-dwelling elderly women aged 50-96 years. Pearson correlation analysis and then stepwise multiple regression analyses were performed to further identify the most significant variables contributing to the variation of fasting and nonfasting TG. RESULTS: Multiple regression analysis for fasting TG as a dependent variable revealed that TTR (standardized ß: 0.299) and HDL cholesterol (standardized ß: -0.545) emerged as determinants of TG independently of percentage of body fat, homeostasis model assessment insulin resistance, serum leptin and adiponectin, and plasminogen activator inhibitor-1 (PAI-1) (R 2 = 0.36). For nonfasting TG, HDL cholesterol (standardized ß: - 0.461), TTR (standardized ß: 0.231), nonfasting insulin, a marker of insulin resistance, (standardized ß: 0.202), and PAI-1 (standardized ß: 0.187) emerged as determinants independently of percentage of body fat, nonfasting glucose, serum leptin and adiponectin, and high-sensitivity C-reactive protein (R 2 = 0.45). CONCLUSIONS: Fasting and nonfasting TG showed positive association with TTR in community-dwelling elderly non-obese women independently of insulin resistance, HDL cholesterol, and adiponectin. These findings may provide a clue as to a physiological function of circulating TTR in human: an influence factor of TG-rich lipoproteins in the circulation.

Higher circulating orosomucoid, an acute-phase protein, and reduced glucose-induced insulin secretion in middle-aged Japanese people with prediabetes.

INTRODUCTION: Circulating orosomucoid, an acute-phase protein, predicted type 2 diabetes mellitus risk in several Western countries. Here, we assessed serum orosomucoid (ORM) in relation to prediabetes in the Japanese. RESEARCH DESIGN AND METHODS: Participants consisted of 83 middle-aged Japanese subjects with normal glucose tolerance (NGT), 37 with prediabetes and 4 with newly identified diabetes, whose homeostasis model assessment-insulin resistance (HOMA-IR) averaged 1.1±0.7, 1.4±0.9 and 1.7±0.8, respectively. Body composition, serum inflammatory markers, adiponectin, ß-cell function and insulin resistance inferred from serum insulin kinetics during an oral glucose tolerance test were compared cross-sectionally between those with prediabetes and NGT. RESULTS: Serum orosomucoid, but not high-sensitivity C reactive protein, was elevated in prediabetes (190±29 vs 141±31 mg/dL) with further elevation in diabetes (295±52 mg/dL) (all p<0.001). Prediabetes was associated with lower Oral Disposition Index (the product of the Insulinogenic Index and Matsuda Index) with further depression in diabetes. No association was found with skeletal muscle mass, HOMA-IR, serum triglyceride, high-density lipoprotein (HDL) cholesterol and adiponectin. CONCLUSIONS: Higher circulating ORM and reduced glucose induced insulin secretion were found in middle-aged Japanese people with prediabetes in the absence of insulin resistance.

Association of ABC (HbA1c, blood pressure and LDL-cholesterol) goal achievement with visit-to-visit ABC variability and postprandial dysmetabolism in type 2 diabetic patients.

BACKGROUND AND OBJECTIVES: Although roles of ABC (HbA1c, blood pressure [BP] and LDL-cholesterol) goal attainment on CVD risk outcomes have been well established, it is less studied whether ABC goal attainment associates with ABC variability, non-traditional risk factors. METHODS AND STUDY DESIGN: Intrapersonal mean levels and standard deviation (SD) of HbA1c, BP and LDL-cholesterol, fasting and post-breakfast plasma glucose (PG) and serum triglyceride (TG) during 12 months were calculated in 168 type 2 diabetes patients (aged 62.3 years, 53.6% men). Associations of ABC goal attainment with non-traditional glycemic, BP and lipid risk factors were analyzed. RESULTS: Among 168 patients, 92 (54.8%), 91 (54.2%) and 111 (66.1%) patients achieved HbA1C, BP and cholesterol goal, respectively, and 47 (28.0 %), 45 (26.8 %), 63 (37.5 %) and 13 (7.7 %) achieved triplegoal, dual-goal, single-goal and no-goal, respectively. Achieving more ABC goals was associated with stepwise decreases in mean levels and SD of fasting and post-breakfast PG, and HbA1c. It was also associated with stepwise decreases in mean levels and SD of fasting and post-breakfast TG, and LDL-cholesterol. Further, achieving more ABC goals was associated with stepwise decreases in brachial pulse pressure and mean levels and SD of systolic BP. CONCLUSIONS: ABC goal achievement was associated with a broad range of non-traditional glycemic, BP and lipid risk factors in type 2 diabetic patients. Reaching more ABC treatment targets may be important for reductions in long-term ABC variability and postprandial dysmetabolism.

Determinants and correlates of adipose tissue insulin resistance index in Japanese women without diabetes and obesity.

INTRODUCTION: Determinants and correlates of a novel index of adipose tissue insulin resistance (AT-IR) (the product of fasting insulin and free fatty acid concentrations) were investigated in Japanese women without diabetes and obesity. RESEARCH DESIGN AND METHODS: Cross-sectional associations of AT-IR with fat mass and distribution, and IR-related cardiometabolic variables were examined in 210 young and 148 middle-aged women whose average body mass index (BMI) was <23 kg/m2 and waist was <80 cm. Multivariate linear regression analyses were used to identify most important determinants of AT-IR. RESULTS: Young and middle-aged women did not differ in AT-IR (3.5±2.7 and 3.2±2.1, respectively). In both young and middle-aged women, AT-IR was positively associated with trunk/leg fat ratio, a sophisticated measure of abdominal fat accumulation, fasting plasma glucose (FPG), fasting triglycerides (FTG), serum alanine aminotransferase and γ-glutamyl-transpeptidase (all p<0.05). Furthermore, in middle-aged but not in young women, AT-IR showed positive associations with BMI, waist, fat mass index, low-density lipoprotein cholesterol, apolipoprotein B and systolic and diastolic blood pressure (BP) (all p<0.05). AT-IR showed no association with hemoglobin A1c, high-density lipoprotein (HDL) cholesterol and apolipoprotein A1 in two groups of women. On multivariate analysis including waist, FPG, FTG, HDL cholesterol and systolic BP as independent variables, FPG, FTG and HDL cholesterol emerged as independent determinants of AT-IR in young women (cumulative R2=0.141) and waist in middle-aged women (cumulative R2=0.056). In a model which included trunk/leg fat ratio instead of waist, trunk/leg fat ratio and systolic BP were determinants of AT-IR in middle-aged women (cumulative R2=0.093). Results did not alter in young women. CONCLUSIONS: AT-IR may be a simple and useful surrogate index of adipose tissue insulin resistance even in populations without diabetes and obesity.

Decreased arterial distensibility and postmeal hyperinsulinemia in young Japanese women with family history of diabetes.

INTRODUCTION: To assess vascular function and characterize insulin secretion using a physiological approach in Japanese women with family history of type 2 diabetes (FHD). RESEARCH DESIGN AND METHODS: Standardized mixed-meal tests were performed with multiple postprandial glucose, insulin and free fatty acids (FFA) measurements over a 30-120 min period in 31 Japanese women aged 21-24 years. Arterial distensibility was assessed as well. RESULTS: Fasting glucose, triglyceride and insulin averaged <90 mg/dL, <60 mg/dL and <5 µU/mL, respectively, and did not differ cross-sectionally between 10 with (FHD+) and 21 without FHD (FHD-). FHD+ showed higher insulin responses not only during the first 30 min (p=0.005) but also during the second hour (60-120 min, p<0,05) in spite of identical postprandial suppression of FFA and identical fasting and postprandial glucose and FFA concentrations, except for higher 60 min FFA in FHD+. Further, FHD+ had decreased arterial distensibility (p=0.003). On multivariate regression analysis, arterial distensibility emerged as the only significant independent predictor of FHD+. Endurance training in FHD+ did not alter decreased arterial distensibility whereas it abolished postprandial hyperinsulinemia. CONCLUSIONS: FHD was associated with decreased arterial distensibility and postprandial hyperinsulinemia despite nearly identical postprandial glycemia and postprandial FFA suppression, suggesting that impaired vascular insulin sensitivity may precede glucose and lipid dysmetabolism in normal weight Japanese women aged 22 years.