Periodontal diseases assessed by average bone resorption are associated with microvascular complications in patients with type 2 diabetes.

Periodontal disease often develops in patients with diabetes, and further exacerbated with diabetic complications. It would be clinically important to clarify the relationship between diabetic microvascular diseases and periodontal disease. This study aimed to evaluate the association between periodontal disease and diabetic complications in patients with type 2 diabetes with poor glycemic control. A total of 447 patients with type 2 diabetes hospitalized at Rakuwakai Otowa Hospital, Japan, were initially recruited in this study. After excluding 134 patients who lacked clinical data or were edentulous, 312 were included in our study. The severity of periodontal disease was evaluated based on the average bone resorption rate. Patients with diabetic nephropathy developed severe periodontal disease (multivariate-adjusted odds ratio, 3.00 [95% CI 1.41-5.19]). Diabetic neuropathy was positively associated with the severity of periodontal disease; the multivariate-adjusted odds ratio (95% CI) was 1.62 (0.87‒2.99) for moderate and 4.26 (2.21‒8.20) for severe periodontal disease. In contrast, diabetic retinopathy was linked with moderate periodontal disease (multivariate-adjusted odds ratio 2.23 [95% CI 1.10-4.10]), but not with severe conditions (multivariate-adjusted odds ratio 0.92 [95% CI 0.67-3.07]). In conclusion, periodontal disease, evaluated by average bone resorption rate, was associated with diabetic nephropathy and neuropathy. Supplementary Information: The online version contains supplementary material available at 10.1007/s13340-022-00591-0.

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.

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.

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.

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.

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.

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.

Association between Psychosocial Factors and Oral Symptoms among Residents in Fukushima after the Great East Japan Earthquake: A Cross-Sectional Study from the Fukushima Health Management Survey.

Oral health is closely related to subjective general health and systemic diseases. This cross-sectional study aimed to identify the factors related to oral symptoms and their worsening in relation to psychosocial factors after the Great East Japan Earthquake. In this study, 64,186 residents aged 15-101 years old, who experienced the earthquake on 11 March 2011, were surveyed regarding their oral symptoms; psychological factors, such as post-traumatic reactions and psychological distress; and social factors such as evacuation, work change, and loss of a close person; history of systemic diseases; and lifestyle. Binomial logistic regression analysis was used to calculate odds ratios, and 95% confidence intervals were established for each factor associated with prevalent and exacerbated oral symptoms. The proportions of participants with prevalent and exacerbated oral symptoms were 10.3% and 1.6%, respectively. The multivariate odds ratios and 95% CI of psychosocial factors associated with exacerbated oral symptoms were as follows: post-traumatic stress disorder symptoms, 2.24 (1.64-3.06); work changes, 1.88 (1.34-2.65); history of dyslipidemia, 1.74 (1.27-2.39); and subjective current poor health condition, 2.73 (2.00-3.75). Psychological factors, social factors, and physical factors were associated with both prevalent and exacerbated oral symptoms.

Evaluation of Dantrolene Granules Extemporaneously Reformulated from Capsules in a Pharmacy.

Dantrolene capsule, an effective therapeutic agent for the treatment of spasticity, is administered to children who cannot swallow the capsule after reformulation into a powder. The powdered drug can alter the specified dosage and it is also difficult to dispense the powdered formulation because of its bulky and sticky nature. To resolve these problems, we reformulated dantrolene capsules into granules using a centrifugal planetary mixer in the pharmacy. The granules containing lactose-cornstarch, D-mannitol, or microcrystalline cellulose as a diluent were examined to determine particle size distribution, flowability, drug content uniformity, and disintegration time. The granules with microcrystalline cellulose were superior to the other forms, owing to their smaller size, good drug content uniformity, and rapid disintegration. We further investigated the usability of the granules in the dispensing procedure (dividing and packing) and in the dosing process (retrieval from package) using the powders as controls. The deviation of the divided amount and loss on dosing were reduced relative to the powders. In addition, drug dissolution properties and storage stability for 12 months were the same as those of the powders. Therefore, we concluded that dantrolene granules are excellent alternatives as an extemporaneous preparation in pharmacies.

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.

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.

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.

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.

Higher circulating orosomucoid and lower early-phase insulin secretion in midlife Japanese with slower glucose disposal during oral glucose tolerance tests.

OBJECTIVE: We examined whether serum orosomucoid, an acute phase protein as with C-reactive protein, in addition to insulin resistance and beta-cell dysfunction, was involved in glucose disposal during oral glucose tolerance tests. RESEARCH DESIGN AND METHODS: 124 midlife Japanese (65 women, 66% with normal glucose tolerance) received dual-energy X-ray absorptiometry and 75 g oral glucose tolerance tests with multiple postload glucose and insulin measurements. Subjects were divided based on the relationship between postload and fasting glucose. Obesity measures, insulin resistance, insulin secretion, serum orosomucoid and adiponectin were cross-sectionally analyzed by analysis of variance and then Bonferroni's multiple comparison procedure. RESULTS: In 10 subjects (group A) and 19 subjects (group B), postload glucose fell below fasting glucose at 1 h and 2 h, respectively. In the remaining 95 subjects (group C), postload glucose never fell below fasting glucose. The insulinogenic index was lower and area under the glucose curve was higher in groups B and C as compared to group A (both p<0.05), whereas the Matsuda index, the homeostasis model assessment of insulin resistance, adipose insulin resistance (the product of fasting free fatty acid and insulin) and area under the insulin curve did not differ. Although there was no difference in fat mass index, trunk/leg fat ratio and adiponectin, orosomucoid was higher in group C as compared to group A (p<0.05). CONCLUSIONS: Lower early-phase insulin secretion and low-grade inflammation were associated with slower glucose disposal during an oral glucose tolerance test in midlife Japanese. The rate of glucose disposal was not related to adiposity and insulin resistance.

Reduced Birth Weight, Decreased Early-Phase Insulin Secretion, and Increased Glucose Concentrations after Oral Glucose Tolerance Test in Japanese Women Aged 20 Years with Family History of Type 2 Diabetes.

INTRODUCTION: We tested the hypothesis that family history of type 2 diabetes (FHD) is associated with reduced birth weight and reduced insulin secretion later in life. MATERIALS AND METHODS: Birth weight, body composition by whole-body dual-energy X-ray absorptiometry, and homeostasis model assessment-insulin resistance were compared between Japanese women aged 20 years with positive (n = 73) and negative (n = 258) FHD. A subsample of 153 women (57 with positive FHD) underwent a 75 g oral glucose tolerance test. Multivariate logistic regression analyses were used to identify the most important determinants of FHD. RESULTS: Women with positive as compared with negative FHD had lower birth weight (3132 ± 364 vs. 3238 ± 418 g, p = 0.04). However, the current fat mass index and trunk/leg fat ratio, sophisticated measures of general and abdominal fat accumulation, respectively, did not differ. Women with positive FHD had a lower insulinogenic index (2.4 ± 7.3 vs. 6.2 ± 16, p = 0.007) and higher area under the glucose curve (217 ± 47 vs. 198 ± 36 mg/dL/2 h, p = 0.006). However, fasting and postload insulinemia, homeostasis model assessment-insulin resistance, and Matsuda index did not differ. In multivariate logistic regression analysis, birth weight was marginally associated with FHD (odds ratio, 0.999; 95% confidential interval, 0.98-1.00000; p = 0.0509). CONCLUSIONS: FHD was associated not only with reduced birth weight but also with decreased early-phase insulin secretion and increased postload glucose concentrations in Japanese women aged 20 years. These findings may be in keeping with the fetal insulin hypothesis and provide some evidence that FHD can alter size at birth, probably through genetic and shared environmental components, which consequently resulted in decreased early-phase insulin secretion and increased glucose excursion in the early twenties. FHD was not related to sophisticated measures of general and abdominal adiposity and insulin resistance/sensitivity.

Associations of ABC (Hemoglobin A1c, Blood Pressure and Low-Density Lipoprotein Cholesterol) Goal Achievement With Chronic Kidney Disease in Type 2 Diabetic Patients With Preserved Kidney Function.

BACKGROUND: We investigated cross-sectional and prospective associations of ABC (hemoglobin A1c (HbA1c), blood pressure and low-density lipoprotein cholesterol) goal attainment with chronic kidney disease. Cross-sectional association with carotid intima-media thickness (IMT) was evaluated as well. METHODS: Prevalence of low estimated glomerular filtration rate (eGFR < 60 mL/min/1.73 m2) and albuminuria (urinary albumin-to-creatinine ratio (ACR) ≥ 30 mg/g) were assessed at baseline and after a median follow-up of 6.0 years in 168 patients with type 2 diabetes with preserved kidney function (aged 62.3 years, 53.6% men). Carotid IMT was measured at baseline only. RESULTS: At baseline, 47 (28.0%), 45 (26.8%), 63 (37.5%) and 13 (7.7%) patients achieved triple-goal, dual-goal, single-goal and no-goal, respectively. Achieving more ABC targets was associated with lower log ACR (P < 0.01), lower percentage of albuminuria (P = 0.02), and lower carotid IMT (P < 0.01) at baseline. Over 6.0 years, eGFR decreased from 76 ± 16 to 67 ± 18 mL/min/1.73 m2 (P < 0.01) whereas ACR levels did not change. There were 32 patients with incident reduced eGFR, eight with GFR stage progression, 15 with progression of albuminuric stages and five with doubling of ACR within the microalbuminuric range. Achieving more ABC targets decreased the percentage of deterioration of GFR stages (30.8%, 28.6%, 24.4% and 14.9%, respectively, P = 0.01). Achieving two or more (8.9% and 8.5%, respectively) compared with one or less ABC targets (15.4% and 15.9%, respectively) was associated with less deterioration of albuminuria (P < 0.001). Although achieving more ABC targets was associated with lower annual decline in eGFR, the difference was not significant. CONCLUSIONS: ABC goal achievement has shown cross-sectional and prospective associations with deterioration of chronic kidney disease in type 2 diabetic patients with preserved kidney function. Cross-sectional association with carotid IMT has been demonstrated as well. Reaching more ABC treatment targets may be important for preventing adverse renal outcomes.

Association of Age and Anemia With Adiponectin Serum Levels in Normal-Weight Japanese Women.

BACKGROUND: Adiponectin serum levels are affected by sex, ethnicities, adiposity, age and several pathological conditions such as anemia. The prevalence of hyperadiponectinemia (≥ 20 mg/L) in relation to anemia (hemoglobin < 12 g/dL) was examined in normal-weight Japanese women. METHODS: Serum adiponectin and blood hemoglobin were measured in 311 young women aged 18 - 24 years (A), 148 of their middle-aged mothers aged 39 - 60 years (B) and 322 community-dwelling women aged ≥ 65 years (C) with a mean body mass index (BMI) of 20.4, 22.0 and 22.4 kg/m2, respectively. Elderly women were subdivided into three age groups: between 65 and 74 years (n = 95, X), between 75 and 84 years (n = 176, Y) and older than 85 years (n = 51, Z). RESULTS: The prevalence of hyperadiponectinemia (A: 3.9%, B: 3.4%, C: 22.7%, P < 0.001) was low and serum adiponectin (A: 11.5 ± 4.3 mg/L, B: 11.8 ± 4.9 mg/L, C: 15.3 ± 7.8 mg/L, P < 0.001) did not change until middle-aged but increased thereafter in a stepwise fashion (X: 18.9%, Y: 22.7%, Z: 35.3%, P = 0.07 and X: 13.9 ± 6.9 mg/L, Y: 15.1 ± 7.7 mg/L, Z: 18.7 ± 8.6 mg/L, P = 0.001, respectively). There were inverse associations of adiponectin with age (r = -0.201, P < 0.001) and hemoglobin (r = -0.318, P < 0.001) in elderly women but not even in young and middle-aged women combined. Furthermore, anemia was associated with higher prevalence of hyperadiponectinemia (34.8% vs. 20.6%, P = 0.01) and higher serum adiponectin (18.3 ± 9.4 mg/L vs. 14.5 ± 7.1 mg/L, P < 0.001) in elderly women but not in younger and middle-aged women. CONCLUSIONS: In normal-weight Japanese women, the prevalence of hyperadiponectinemia and serum adiponectin were increased and associated with anemia at 65 years of age and older.

Higher circulating adiponectin and lower orosomucoid were associated with postload glucose ≤70 mg/dL, a possible inverse marker for dysglycemia, in young Japanese women.

Objective: To examine whether serum adiponectin and orosomucoid were associated with postload glucose ≤70 mg/dL during an oral glucose tolerance test (OGTT), termed as postload low glycemia, a possible inverse marker for dysglycemia. Research design and methods: 75 g OGTTs were performed with multiple postload glucose and insulin measurements over a 30-120 min period in 168 normal-weight Japanese women (18-24 years). Insulin resistance (IR) and ß-cell function inferred from serum insulin kinetics during OGTT, fat mass and distribution by dual-energy X-ray absorptiometry (DXA), serum adiponectin and inflammatory markers were compared cross-sectionally between 39 women with and 129 women without postload low glycemia. Results: Of 168 women, 161 had normal glucose tolerance. Women with as compared with those without postload low glycemia had lower fasting and postload glycemia despite similar fasting and postload insulinemia. They had higher insulinogenic index (p=0.03) and lower adipose IR (a product of fasting free fatty acid and insulin, p=0.01), although DXA-derived general and central adiposity, the Matsuda Index and homeostasis model assessment-IR did not differ. In addition, they had higher adiponectin and lower orosomucoid (both p<0.001). Multivariate logistic regression analyses revealed that adiponectin (OR: 1.14, 95% CI 1.03 to 1.26, p=0.009) and orosomucoid (0.96, 0.93 to 0.97, p=0.008) were associated with postload low glycemia independently of adipose IR and insulinogenic index. Conclusions: Higher adiponectin and lower orosomucoid were associated with 70 or lower mg/dL of postload glucose, a possible inverse marker for dysglycemia, in young women independently of DXA-derived fat mass and distribution, insulin secretion and IR.