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Introduction: Waist circumference (WC) and fasting plasma glucose (FPG) have been demonstrated as risk factors for type 2 diabetes mellitus (T2DM). Evidence is limited regarding the association of the combination of WC and FPG (WyG) with the risk of T2DM. The primary aim of the study was to investigate the relationship between WyG and T2DM. Research design and methods: The current study was a population-based cohort study using data from the NAGALA database. Participants were divided into tertiles based on WyG. Cox proportional hazard regression model was applied to identify the association of WyG with T2DM. Results: During a median follow-up of 6.19 years in the normoglycemia group and 5.58 years in the prediabetes group, respectively, 88 and 285 individuals in the two groups received a diagnosis of T2DM. After full adjustment, risk of T2DM increased in step-wise fashion with increasing tertiles of WyG. For a per-SD increase in WyG, the hazard ratios for T2DM were 3.05 (95% CI 2.64 - 3.51) in all populations, 1.94 (95% CI 1.46 - 2.58) in the normoglycemia group and 1.63 (95% CI 1.40 - 1.90) in the prediabetes group. The interaction between WyG and fatty liver on T2DM was statistically significant in the prediabetes group (P for interaction = 0.034). Conclusions: Elevated WyG was independently associated with incident T2DM in Japan. Baseline WyG help identify individuals at high risk of T2DM and implement effective preventive measures. [ABSTRACT FROM AUTHOR]

Background. Insulin resistance is a risk factor for sarcopenia. The triglycerides (TG)/high-density lipoprotein cholesterol (HDL-C) ratio is an indirect indicator of insulin resistance. We aimed to assess the association between sarcopenia and the TG/HDL-C ratio in Japanese older adults. Methods: Older adults in Wakasa town, Fukui, Japan, were examined between June 2019 and November 2021. We collected data regarding age, sex, height, weight, body mass index, muscle mass, fat mass, muscle mass to fat mass ratio, appendicular lean muscle mass, skeletal muscle mass index, glycated haemoglobin, TG, HDL-C, low-density lipoprotein cholesterol, TG/HDL-C ratio, 5-m gait speed, and grip strength (both sides). Sarcopenia was defined in accordance with the 2019 criteria of the Asian Working Group for Sarcopenia via grip strength, gait speed, and skeletal muscle indices. Results: In total, 65 men and 93 women (mean age, 78 years) were classified as normal (n=114), pre-sarcopenic (n=35), or sarcopenic (n=9). Compared with the normal and pre-sarcopenia groups, the sarcopenia group had the lowest HDL-C level (p=0.013) and highest TG/HDL-C ratio (p=0.008). Risk factors associated with sarcopenia were age (odds ratio=1.35, p=0.002) and the TG/HDL-C ratio (odds ratio=1.62, p=0.008). Conclusions: Older age and an elevated TG/HDL-C ratio are risk factors for sarcopenia. An elevated TG/HDL-C ratio may indicate progression from pre-sarcopenia to sarcopenia. [ABSTRACT FROM AUTHOR]

Background: Insulin resistance (IR) plays a crucial role in the occurrence and progression of diabetes. This study aimed to evaluate and compare the predictive value of four IR surrogates, including the triglycerides glucose (TyG) index, TyG and body mass index (TyG-BMI), triglycerides/high-density lipoprotein cholesterol (TG/HDL-C) ratio, and the metabolic score for IR (MetS-IR) for diabetes in two large cohorts. Methods: A total of 116,661 adult participants from the China Rich Healthcare Group and 15,464 adult participants from the Japanese NAGALA cohort were included in the study. Multivariable Cox proportional hazards models were used to assess the standardized hazard ratio (HR) of the TyG index, TyG-BMI, TG/HDL-C ratio, and MetS-IR directly associated with diabetes. Receiver operating characteristic (ROC) curve and time-dependent ROC curve analysis were performed to evaluate and compare the predictive value of the four IR surrogates for diabetes. Results: In the two independent cohorts, the average follow-up time was 3.1 years in the China cohort, with 2681(2.30%) incident cases of diabetes recorded, and 6.13 years in the Japan cohort, with 373 incident cases (2.41%) of diabetes recorded. After adjusting for potential confounding factors, we found that among the four IR surrogates, TyG-BMI and MetS-IR showed stronger associations with diabetes. The stronger associations persisted even after further stratification by age, sex, hypertension, and obese subgroups. In terms of diabetes prediction, based on ROC analysis, TyG-BMI demonstrated the highest predictive accuracy for diabetes in the Chinese population, while both TyG-BMI and MetS-IR showed the highest predictive accuracy in the Japanese population. The results of further subgroup ROC analysis confirmed the robustness of these findings. Furthermore, the time-dependent ROC results indicated that among the four IR surrogates, MetS-IR exhibited the highest accuracy in predicting future diabetes at various time intervals in the Japanese population. Conclusion: Our findings suggest that evaluating TyG-BMI and MetS-IR as IR surrogates may be the most useful for predicting diabetes events and assessing the risk of developing diabetes in East Asian populations. [ABSTRACT FROM AUTHOR]

Background: Body mass index (BMI) and fasting plasma glucose (FPG) are known risk factors for type 2 diabetes mellitus (T2DM), but data on the prospective association of the combination of BMI and FPG with T2DM are limited. This study sought to characterize the association of the combination of BMI and FPG (ByG) with T2DM. Methods: The current study used the NAGALA database. We categorized participants by tertiles of ByG. The association of ByG with T2DM was expressed with hazard ratios (HRs) with 95% confidence intervals (CIs) after adjustment for potential risk factors. Results: During a median follow-up of 6.19 years in the normoglycemia cohort and 5.58 years in the prediabetes cohort, the incidence of T2DM was 0.75% and 7.79%, respectively. Following multivariable adjustments, there were stepwise increases in T2DM with increasing tertiles of ByG. After a similar multivariable adjustment, the risk of T2DM was 2.57 (95% CI 2.26 - 2.92), 1.97 (95% CI 1.53 - 2.54) and 1.50 (95% CI 1.30 - 1.74) for a per-SD change in ByG in all populations, the normoglycemia cohort and the prediabetes cohort, respectively. Conclusion: ByG was associated with an increased risk of T2DM in Japan. The result reinforced the importance of the combination of BMI and FPG in assessing T2DM risk. [ABSTRACT FROM AUTHOR]

Introduction: Insulin resistance syndrome and lipoatrophic diabetes are characterized by severe insulin resistance and are often refractory to treatment. Trials assessing the efficacy of antidiabetes drugs for these rare conditions have been limited, however. Sodium-glucose cotransporter 2 (SGLT2) inhibitors, which lower glycemia independently of insulin action, have shown efficacy for type 2 diabetes with insulin resistance. We here investigated the efficacy and safety of the SGLT2 inhibitor empagliflozin for treatment of insulin resistance syndrome and lipoatrophic diabetes. Methods: The trial was conducted at five academic centers in Japan and included seven patients with insulin resistance syndrome and one patient with lipoatrophic diabetes. Participants received 10 mg of empagliflozin daily. If the hemoglobin A1c (HbA1c) level was ≥ 7.0% (52 mmol/mol) after 12 weeks, the dose was adjusted to 25 mg. The study duration was 24 weeks, and the primary outcome was the change in HbA1c level by the end of the treatment period. Safety evaluations were performed for all participants. Results: By the end of the 24-week treatment period, the mean HbA1c level for all eight patients had decreased by 0.99 percentage points (10.8 mmol/mol) (95% confidence interval [CI], 0.59 to 1.38 percentage points, 6.6 to 14.9 mmol/mol) and the mean fasting plasma glucose concentration had declined by 63.9 mg/dL (3.55 mmol/L) (95% CI 25.5 to 102.3 mg/dL, 1.42 to 5.68 mmol/L). Continuous glucose monitoring revealed a reduction in mean glucose levels from 164.3 ± 76.1 to 137.6 ± 46.6 mg/dL (9.13 ± 4.23 to 7.65 ± 2.59 mmol/L) as well as an increase in the time in range (70–180 mg/dL) from 58.9 ± 36.1% to 70.8 ± 18.3%. Seventeen mild adverse events were recorded in five individuals throughout the study period. No severe events were reported. The mean body mass showed a slight decrease and the mean serum ketone body concentration showed a slight increase during treatment. Conclusion: Our results demonstrate that empagliflozin shows a certain level of efficacy and safety for treatment of insulin resistance syndrome and lipoatrophic diabetes. Trial Registration: jRCTs2051190029 and NCT04018365. [ABSTRACT FROM AUTHOR]

Context Branched-chain amino acids (BCAA) are substrates for protein synthesis. Although their intake may contribute to an increase in skeletal muscle mass, elevated serum BCAA levels have been reported to be associated with insulin resistance, potentially resulting in decreased skeletal muscle mass. Objective This study aimed to explore the association between elevated serum BCAA levels and longitudinal skeletal muscle loss. Design and Setting A cohort analysis was conducted, in which serum amino acids were analyzed in healthy individuals who underwent a medical health checkup at Kameoka Municipal Hospital (HOZUGAWA study), Japan. Patients Seventy-one participants (37 men and 34 women) underwent follow-up checkups after the baseline visit. The follow-up duration was 1.2 ±.4 years. Main Outcome Measures The relationship between fasting baseline serum BCAA levels and lifestyle factors, body composition, blood test results, dietary history, and changes in skeletal muscle mass was evaluated. Results In both men and women, serum BCAA levels were positively correlated with body weight, body mass index, skeletal muscle mass index (SMI), and serum triglycerides but inversely correlated with serum high-density lipoprotein cholesterol. In men, fasting serum BCAA levels were inversely associated with the rate of change in SMI (adjusted β = −.529, P =.006), and elevated BCAA levels were independently associated with a longitudinal decrease in skeletal muscle mass (odds ratio: 1.740; 95% confidence interval: 1.023-2.960 per 50 nmol/mL serum BCAAs increase). Conclusion Increased circulating BCAAs could be an indicator of skeletal muscle loss in men. [ABSTRACT FROM AUTHOR]

Aim: This study examined the association between the metabolic score for insulin resistance (METS-IR), a novel surrogate indicator of insulin resistance, and brachial-ankle pulse wave velocity (baPWV) in Japanese health check participants. Methods: A cross-sectional research was conducted involving individuals in a program of medical health screening at the Medical Health Check-up Center in Japan. The study assessed the connection between METS-IR and baPWV in 912 participants who joined the program between 3/1/2004 and 12/31/2012. Serum laboratory tests and lifestyle surveys were the covariates. Multivariate linear regression analysis and subgroup analyses were performed. Results: 912 participants were involved in this cross-sectional study. Adjusted for age, sex, BMI, AST, UA, HDL, eGFR, ankle-brachial index (ABI), alcohol consumption, and smoking status, multivariate linear regression analysis showed that METS-IR and baPWV showed a significant positive association (adjusted β=15.3, 95% confidence interval (CI): 6.61-23.98) with METS-IR as a continuous variable. When converting METS-IR to quartile categorical variables, higher quartile METS-IR indices had longer baPWV (Q3 vs Q1, β=86.14, 95% CI: 23.45-148.83; Q4 vs Q1, β=125.41, 95% CI: 39.99-210.84). In subgroup analysis, METS-IR was associated with baPWV in people with eGFR > 60 ml/min (adjusted β= 14.44, 95% CI: 5.61-23.26, P=0.001), none or light alcohol consumption (adjusted β=16.92, 95% CI: 6.85-27, P=0.001), non-smokers (adjusted β=15.48, 95% CI: 5.86-25.1, P=0.002), non-regular exercisers(adjusted β=17.34, 95% CI: 8.03-26.65, P<0.001), non-fatty liver (adjusted β=17.65, 95% CI: 5.92-29.39, P=0.003), and non-hypertensive (adjusted β=16.13, 95% CI:8.45-23.8, P<0.001). Conclusion: METS-IR are remarkably associated with baPWV among health check-up participants in Gifu, Japan. As a simple, easily calculated predictor of arterial stiffness, METS-IR could be considered for primary care as a monitoring tool to identify people with high risk of cardiovascular disease in order to intervene early on risk factors. Future prospective, large-sample researches are still needed to confirm this. [ABSTRACT FROM AUTHOR]

Metabolic diseases, including obesity, diabetes, and fatty liver disease, are dramatically increasing around the world. Seaweed is low in calories and rich in many active ingredients that are necessary for maintaining good health, and is expected to be effective for preventing metabolic diseases. The purpose of this study was to examine the effects of a traditional Japanese edible seaweed Hypnea asiatica (H. asiatica) on obesity, using a mouse model. H. asiatica was dried and powdered, mixed with a high-fat diet, and fed to male C57BL/6J mice for 13 weeks. On the last day of the experiment, blood samples were collected under anesthesia and biochemical parameters such as lipids and adipokines were measured. Liver and adipose tissue were excised, weighed, and oxidant/antioxidant parameters were measured. Some mice were perfused with a fixative solution containing formalin, and tissue specimens were prepared. A glucose tolerance test was used to assess insulin resistance. The inhibition of lipase activity was evaluated in vitro. Thirteen-week supplementation with H. asiatica suppressed body weight gain, body fat accumulation, and blood glucose levels. H. asiatica also improved fatty liver and hypercholesterolemia, and reduced the oxidant and inflammatory parameters of serum and liver. H. asiatica increased fecal triglyceride excretion and polyphenol-rich ethanol extract of H. asiatica inhibited lipase activity in vitro. These results suggest that polysaccharides and polyphenols in H. asiatica may ameliorate obesity and diabetes by inhibiting intestinal fat absorption and reducing oxidative stress and inflammation. H. asiatica may be useful in preventing metabolic diseases such as obesity, diabetes, and fatty liver. [ABSTRACT FROM AUTHOR]

Summary: This study aimed to investigate how the COVID‐19 pandemic since 2020 has affected the homeostasis model assessment of insulin resistance (HOMA‐IR), body mass index (BMI) and degree of obesity among Japanese children. HOMA‐IR, BMI and degree of obesity were calculated for 378 children 14–15 years old (boys/girls, 208/170) who underwent checkups during 2015–2021. Changes in these parameters over time and correlations between parameters were assessed, and the proportions of participants with IR (HOMA‐IR ≥2.5) were compared. HOMA‐IR values increased significantly over the study period (p < 0.001), with a significantly large proportion of participants with IR in 2020–2021 (p < 0.001). Conversely, BMI and degree of obesity did not change significantly. HOMA‐IR did not correlate with BMI or degree of obesity during 2020–2021. In conclusion, the COVID‐19 pandemic may have had an impact on the increase in the proportion of children with IR, regardless of BMI or degree of obesity. [ABSTRACT FROM AUTHOR]

High fish consumption may be associated with lower inflammation, suppressing atherosclerotic CVD (ASCVD). Long sleep duration, as well as short sleep, may contribute to inflammation, thus facilitating ASCVD. This study investigated the overall association between fish consumption, sleep duration and leucocytes count. We conducted a cross-sectional study between April 2019 and March 2020 with a cohort of 8947 apparently healthy participants with no history of ASCVD (average age, 46·9 ± 12·3 years and 59 % males). The average frequency of fish consumption and sleep duration were 2·13 ± 1·26 d/week and 6·0 ± 0·97 h/d. Multivariate linear regression analysis revealed that increased fish consumption was an independent determinant of sleep duration (β = 0·084, P < 0·0001). Additionally, habitual aerobic exercise (β = 0·059, P < 0·0001) or cigarette smoking (β = −0·051, P < 0·0001) and homoeostasis model assessment-insulin resistance (HOMA-IR) (β = −0·039, P = 0·01) were independent determinants of sleep duration. Furthermore, multivariate linear regression analysis identified fish consumption as an independent determinant of leucocytes count (β = −0·091, P < 0·0001). However, a significant U-shaped curve was found between leucocytes count and sleep duration, with 6–7 h of sleep as the low value (P = 0·015). Higher fish consumption may be associated with a lower leucocytes count in the presence of adequate sleep duration and healthy lifestyle behaviors. However, long sleep duration was also related to increased inflammation, even in populations with high fish consumption. Further studies are needed to clarify the causality between these factors. [ABSTRACT FROM AUTHOR]

Aim: Identifying plasma molecules associated with skeletal muscle properties can elucidate the pathophysiology of sarcopenia. Because adipocytokines are a promising candidate marker, the current study aimed to clarify the possible associations between adiponectin and leptin levels and mid‐thigh muscle cross‐sectional area and mean attenuation value, which are indices of muscle mass and fat deposition in muscle, respectively. Methods: The current study included 1440 older Japanese adults (mean age 69.3 years). Mid‐thigh skeletal muscle cross‐sectional area and mean attenuation value were evaluated through computed tomography scan. A low attenuation value showed a greater fat deposition in muscle. Circulating adiponectin and leptin levels were assessed using blood specimens collected during the baseline investigation. Results: Plasma leptin level was inversely correlated with muscle cross‐sectional area, but not with attenuation value. The association with cross‐sectional area was independent of possible confounding factors including body size (Q1: reference; Q2: β = −0.032, P = 0.033; Q3: β = −0.064, P < 0.001; Q4: β = −0.111, P < 0.001). In contrast, adiponectin level was independently and inversely associated with attenuation value (Q1: reference; Q2: β = −0.044, P = 0.122; Q3: β = −0.080, P = 0.006; Q4: β = −0.159, P < 0.001), but not with cross‐sectional area. These associations between adipocytokine levels and muscle properties were independent of abdominal fat area and insulin resistance. Conclusions: There were adiposity‐ and insulin resistance‐independent associations between adipocytokines levels and skeletal muscle mass and fat deposition in muscle, suggesting an involvement of adipocytokines in muscle properties. Geriatr Gerontol Int 2023; 23: 444–449. [ABSTRACT FROM AUTHOR]

Aims/Introduction: To investigate the genetic background of Japanese patients with suspected maturity‐onset diabetes of the young (MODY). Materials and Methods: On 340 proband patients referred from across Japan, genomic variants were analyzed using a targeted multigene panel analysis combined with the multiplex ligation probe amplification (MLPA) analysis, mitochondrial m.3243A > G analysis and methylation‐specific polymerase chain reaction of the imprinted 6q24 locus. Pathogenic/likely pathogenic variants were listed according to the 2015 American College of Medical Genetics and Genomics and the Association for Molecular Pathology criteria. Additionally, variants with a population frequency <0.001 and Combined Annotation Dependent Depletion score >20 (CS >20) were listed as rare variants of uncertain significance‐CS >20. Results: A total of 157 pathogenic/likely pathogenic variants and 44 rare variants of uncertain significance‐CS >20 were identified. In the pathogenic/likely pathogenic variants, alterations in the GCK gene were the most common (82, 52.2%) followed by HNF1A (29, 18.5%), HNF4A (13, 8.3%) and HNF1B (13, 8.3%). One patient was a 29.5% mosaic with a truncating INSR variant. In the rare variants of uncertain significance‐CS >20, 20 (45.5%) were in the genes coding for the adenosine triphosphate‐sensitive potassium channel, KCNJ11 or ABCC8, and four were in the genes of the insulin‐signaling pathway, INSR and PIK3R1. Four variants in ABCC8 were previously reported in patients with congenital hyperinsulinism, suggesting the inactivating nature of these variants, and at least two of our patients had a history of congenital hyperinsulinism evolving into diabetes. In two patients with INSR or PIK3R1 variants, insulin resistance was evident at diagnosis. Conclusions: Causative genomic variants could be identified in at least 46.2% of clinically suspected MODY patients. ABCC8‐MODY with inactivating variants could represent a distinct category of MODY. Genes of insulin resistance should be included in the sequencing panel for MODY. [ABSTRACT FROM AUTHOR]

Background: Diabetes and the etiology of breast cancer are clearly associated. However, the impact of diabetes on prognosis is not yet understood. Therefore, we conducted a retrospective cohort study to examine the relationship between diabetes and patient outcomes in breast cancer patients. Methods: We investigated 332 Japanese women with breast cancer who underwent curative surgery at our hospital. Patients without sufficient clinical information including hemoglobin A1c (HbA1c) and those with an observation period of less than 1 year were excluded. Results: Among the patients examined, 106 had diabetes at the time of their breast cancer diagnosis. Among the 296 patients with invasive breast carcinoma, 36 patients developed distant metastases during the mean observation period of 45 months. Sixteen patients died due to breast cancer, while 13 died of other causes. Multivariate analysis revealed that diabetes, tumor size, and estrogen receptor (ER) status were independent factors related to distant metastasis-free survival (DMFS) (p = 0.038, p < 0.001, and p = 0.006, respectively). Kaplan-Meier curve analysis revealed that diabetes negatively affected the outcomes of ER-negative breast cancer patients both in DMFS and overall survival (p = 0.045 and p = 0.029, respectively). Meanwhile, patient outcomes did not differ according to the level of HbA1c in diabetes patients. Conclusion: Patients with diabetes had a significantly shorter DMFS, and the negative effect of diabetes on patient outcomes was more evident in ER-negative breast cancer. Our data indicates the importance of primary prevention of diabetes for breast cancer patients. [ABSTRACT FROM AUTHOR]

The present study investigated the associations of serum gamma-glutamyl transferase (GGT), a marker of fatty liver and oxidative stress, and ALT/AST, a marker of fatty liver, with percentage trunk fat and postload glucose, insulin resistance, and β-cell function in middle-aged Japanese individuals, whose BMI averaged < 23.0 kg/m 2 . Pancreatic β-cell function was assessed using the disposition index calculated by a product of the insulinogenic index (IGI) and Matsuda insulin sensitivity index, a biomarker of early-phase glucose-stimulated insulin secretion and whole-body insulin sensitivity, respectively. Multivariate linear regression analyses revealed that the disposition index was associated inversely with GGT independently of percentage trunk fat, homeostasis model assessment insulin resistance (HOMA-IR), a marker of insulin resistance, and Matsuda index. When IGI was included instead of the disposition index, IGI (inversely) and HOMA-IR were associated with GGT independently of percentage trunk fat and Matsuda index. When the area under the glucose concentration curve (AUCg) during an oral glucose tolerance test was included instead of the disposition index, AUCg and HOMA-IR emerged as independent determinants of GGT. ALT/AST was associated with HOMA-IR alone. Results suggest a different pathophysiologic basis between GGT and ALT/AST in predicting diabetic risk in non-obese Japanese., (© 2024. The Author(s).)

The relationship of adipose tissue insulin resistance (AT-IR, a product of fasting insulin and free fatty acids) and homeostasis-model assessment-insulin resistance (HOMA-IR) to β-cell function was studied cross-sectionally in the setting of subtle glucose dysregulation. Associations of AT-IR and HOMA-IR with fasting and post-glucose glycemia and β-cell function inferred from serum insulin kinetics during a 75 g oral glucose tolerance test were studied in 168 young female Japanese students. β-cell function was evaluated by disposition index calculated as a product of the insulinogenic index (IGI) and Matsuda index. AT-IR, not HOMA-IR, showed positive associations with post-glucose glycemia and area under the glucose response curve although both indices were associated with fasting glycemia. HOMA-IR, not AT-IR, was associated positively with log IGI whereas both indices were inversely associated with Matsuda index. AT-IR, not HOMA-IR, showed inverse associations with log disposition index. Associations of adipose tissue insulin resistance with β-cell function (inverse) and glucose excursion in young Japanese women may suggest that lipotoxicity to pancreatic β-cells for decades may be associated with β cell dysfunction found in Japanese patients with type 2 diabetes. Positive association of HOMA-IR with insulinogenic index may be associated with compensatory increased insulin secretion., (© 2024. The Author(s).)

Associations of adipose tissue insulin resistance index (AT-IR, a product of fasting insulin and free fatty acids) with body fat mass and distribution and appendicular skeletal muscle mass (ASM) were compared with results of homeostasis-model assessment-insulin resistance (HOMA-IR) in 284 Japanese female university students and 148 their biological mothers whose BMI averaged < 23 kg/m 2 . Although mothers compared with daughters had higher BMI, body fat percentage, trunk fat to body fat (TF/BF) ratio and lower leg fat to body fat (LF/BF), AT-IR and HOMA-IR did not differ. We had multivariable linear regression analyses which included TF/BF ratio, LF/BF ratio, weight-adjusted ASM (%ASM), height-adjusted ASM index (ASMI), fat mass index (FMI), and body fat percentage. In young women, AT-IR was independently associated with LF/BF ratio (Standardized β [Sβ]: - 0.139, p = 0.019) and ASMI (Sβ: - 0.167, p = 0.005). In middle-aged women, LF/BF ratio (Sβ: - 0.177, p = 0.049) and %ASM (Sβ: - 0.205, p = 0.02) emerged as independent determinants of AT-IR. HOMA-IR was associated with TF/BF ratio and FMI, a proxy of abdominal and general adiposity, respectively, in both young and middle-aged women. The inverse association of AT-IR with leg fat may support the notion that limited peripheral adipose storage capacity and small skeletal muscle size are important etiological components in insulin-resistant cardiometabolic disease in Japanese women., (© 2024. The Author(s).)

Aims: Nonalcoholic fatty liver disease (NAFLD) is known to be associated with atherosclerosis. This study focused on upstream changes in the process by which NAFLD leads to atherosclerosis. The study aimed to confirm the association between NAFLD and the cardio-ankle vascular index (CAVI), an indicator of subclinical atherosclerosis, and explore metabolites involved in both by assessing 94 plasma polar metabolites., Methods: A total of 928 Japanese community-dwellers (306 men and 622 women) were included in this study. The association between NAFLD and CAVI was examined using a multivariable regression model adjusted for confounders. Metabolites commonly associated with NAFLD and CAVI were investigated using linear mixed-effects models in which batch numbers of metabolite measurements were used as a random-effects variable, and false discovery rate-adjusted p-values were calculated. To determine the extent to which these metabolites mediated the association between NAFLD and CAVI, mediation analysis was conducted., Results: NAFLD was positively associated with CAVI (coefficients [95% Confidence intervals (CI)]=0.23 [0.09-0.37]; p=0.001). A total of 10 metabolites were involved in NAFLD and CAVI, namely, branched-chain amino acids (BCAAs; valine, leucine, and isoleucine), aromatic amino acids (AAAs; tyrosine and tryptophan), alanine, proline, glutamic acid, glycerophosphorylcholine, and 4-methyl-2-oxopentanoate. Mediation analysis showed that BCAAs mediated more than 20% of the total effect in the association between NAFLD and CAVI., Conclusions: NAFLD was associated with a marker of atherosclerosis, and several metabolites related to insulin resistance, including BCAAs and AAAs, could be involved in the process by which NAFLD leads to atherosclerosis.

Aims: We report the key factors that motivate reluctant Japanese people with type 2 diabetes (T2D) to initiate insulin treatment.Methods: Participants were asked questions pertaining to 2 primary areas of exploration in a concurrent mixed methods approach: (a) understanding people's thoughts and perceptions before and after insulin initiation and any related factors; and (b) exploring the reasons behind people's responses. Data were analyzed using Steps for Coding and Theorization.Results: Participant responses broadly related to 3 themes which influence insulin initiation; 1. Advice from a health care provider (HCP) that insulin is an appropriate treatment; 2. Demonstration by HCPs on how to use the insulin pen/needle and the injection process; and 3. Resignation/surrender/acceptance of insulin, where participants felt there was no other choice but to commence insulin.Conclusions: Based on the 3 identified themes, it is important for HCPs to explain the benefits of insulin and demonstrate and explain the injection procedure to reluctant Japanese people with T2D. We also identified resignation/surrender/acceptance of insulin as a reason for treatment commencement. This study provides important information to assist HCPs in helping reluctant Japanese people with T2D to initiate basal insulin therapy. [ABSTRACT FROM AUTHOR]

Although sodium-glucose cotransporter 2 (SGLT2) inhibitors lower serum uric acid, their long-term effect on uric acid metabolism is not well understood. We analyzed pooled data from studies wherein patients with type 2 diabetes mellitus received luseogliflozin, an SGLT2 inhibitor. Upon stratifying patients by baseline glycated hemoglobin (HbA1c) or serum uric acid, lower HbA1c or higher serum uric acid level was associated with a greater reduction in serum uric acid after treatment. At week 12 of treatment, significant increases in urinary glucose/creatinine (Cr) ratio and urinary uric acid clearance/Cr clearance ratio (CUA/CCr ratio) and a significant reduction in serum uric acid were observed. Comparison of the subgroups of patients with a reduction or an increase in serum uric acid showed that the increase subgroup had a higher estimated glomerular filtration rate (eGFR) at baseline, and the eGFR was significantly reduced, associated with a significant reduction in the CUA/CCr ratio. Multiple regression analysis showed that the reduction in serum uric acid in the luseogliflozin group was strongly associated with baseline high serum uric acid, low HbA1c levels, and an increase in eGFR. Luseogliflozin was shown to reduce serum uric acid by enhancing urinary uric acid excretion in association with increased urinary glucose. Treatment with luseogliflozin resulted in increased serum uric acid in some patients, which may be due to reduced glomerular filtration of uric acid via the tubuloglomerular feedback. SGLT2 inhibitors reduced serum uric acid desirably in patients with type 2 diabetes mellitus with low HbA1c and high serum uric acid. [ABSTRACT FROM AUTHOR]

Background: The obesity epidemic has become a serious public health problem in many countries worldwide. Seaweed has few calories and is rich in active nutritional components necessary for health promotion and disease prevention. The aim of this study was to investigate the effects of the Campylaephora hypnaeoides J. Agardh (C. hypnaeoides), an edible seaweed traditionally eaten in Japan, on high-fat (HF) diet-induced obesity and related metabolic diseases in mice. Methods: Male C57BL/6J mice were randomly divided into the following groups: normal diet group, HF diet group, HF diet supplemented with 2% C. hypnaeoides, and HF diet supplemented with 6% C. hypnaeoides. After 13 weeks of treatment, the weight of the white adipose tissue and liver, and the serum levels of glucose, insulin, adipokines, and lipids were measured. Hepatic levels of adipokines, oxidant markers, and antioxidant markers were also determined. Insulin resistance was assessed by a glucose tolerance test. Polysaccharides of C. hypnaeoides were purified and their molecular weight was determined by high-performance seize exclusion chromatography. The anti-inflammatory effects of purified polysaccharides were evaluated in RAW264.7 cells. Results: Treatment of HF diet-induced obese mice with C. hypnaeoides for 13 weeks suppressed the increase in body weight and white adipose tissue weight. It also ameliorated insulin resistance, hyperglycemia, hepatic steatosis, and hypercholesterolemia. The ingestion of an HF diet increased serum levels of malondialdehyde (MDA), tumor necrosis factor α (TNF-α), and monocyte chemoattractant protein-1 (MCP-1), while it decreased serum adiponectin levels. In the liver, an HF diet markedly increased the MDA, TNF-α, and interleukin-6 (IL-6) levels, while it decreased glutathione and superoxide dismutase. These metabolic changes induced by HF diet feeding were ameliorated by dietary C. hypnaeoides. Purified polysaccharides and ethanol extract from C. hypnaeoides inhibited the lipopolysaccharide-induced overproduction of nitric oxide and TNF-α in macrophage RAW264.7 cells. Conclusions: The present results indicated that C. hypnaeoides was able to alleviate HF diet-induced metabolic disorders, including obesity, hyperglycemia, hepatic steatosis, and hypercholesterolemia by attenuating inflammation and improving the antioxidant capacity in mice. Polysaccharides and polyphenols may be involved in these beneficial effects of C. hypnaeoides. [ABSTRACT FROM AUTHOR]

Diabetes mellitus (DM) is a major risk and prognostic factor for heart failure (HF). Insulin resistance (IR) is an important component of DM, but the relationship between IR and HF prognosis has not yet been established across a wide variety of HF populations. We retrospectively evaluated the relationship between IR and clinical outcomes of HF patients at our hospital between 2017 and 2021. IR was defined as a homeostatic model assessment of IR (HOMA-IR) index ≥ 2.5, calculated from fasting blood glucose and insulin concentrations. The primary outcome was a composite of all-cause death and hospitalisation for HF (HHF). Among 682 patients included in the analyses, 337 (49.4%) had IR. The median age was 70 [interquartile range (IQR): 59-77] years old, and 66% of the patients were men. Among the patients, 41% had a left ventricular ejection fraction below 40%, and 32% had DM. The median follow-up period was 16.5 [IQR: 4.4-37.3] months. IR was independently associated with the primary outcome (HR: 1.91, 95% CI: 1.39-2.62, p < 0.0001), death (hazard ratio [HR]: 1.86, 95% confidence interval [CI]: 1.28-2.83, p < 0.01), and HHF (HR: 1.91, 95% CI: 1.28-2.83, p < 0.01). HOMA-IR is an independent prognostic factor of HF in a wide variety of HF populations.

Background and Aims: Diameter, plaque score, and resistance index (RI) in the common carotid artery (CCA) are indicators of arterial remodeling, atherosclerosis, and vascular resistance, respectively. This study investigated the longitudinal association between adipose tissue insulin resistance or serum free fatty acid (FFA) levels and the CCA parameters., Methods: This retrospective cohort analysis included 1089 participants (mean age 57.6 years; 40.0 % women) with data on health checkups from January 1982 to March 2003 and carotid artery ultrasonography from January 2015 to June 2019. Baseline serum FFA and immunoreactive insulin levels were assessed before and 30, 60, and 120 min after glucose ingestion. Adipose insulin resistance index (Adipo-IR) was calculated as the product of fasting serum insulin and FFA levels. An RI value >0.75 was defined as high RI., Results: A significant association was found between Adipo-IR and RI; however, Adipo-IR showed no association with CCA diameter or plaque score. The incidence of high RI increased with Adipo-IR quartile (Q) groups (47.3 % in Q1, 52.8 % in Q2, 53.3 % in Q3, 62.4 % in Q4; Cochrane-Armitage test for trend, p < 0.001). In multivariate analysis, Adipo-IR levels (Q4 vs. Q1 odds ratio: 1.67, 95 % confidence interval: 1.12-2.51) were positively associated with high RI incidence. Moreover, a significant association was found between RI and serum FFA levels after glucose intake, but not fasting FFA levels., Conclusions: Future vascular resistance was predicted by insulin resistance in the adipose tissue. After glucose intake, serum FFA levels may significantly impact vascular resistance development., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Aims: The aim of the present study is to estimate insulin resistance (IR) using clinically available parameters except for serum insulin or C-peptide concentration to overcome the limitation of homeostasis model assessment of IR (HOMA-IR), which has been widely used in clinical practice. Patients and Methods: Fifty-two admitted patients with type 2 diabetes or impaired glucose tolerance were enrolled, and steady state plasma glucose (SSPG) method and cookie meal tolerance test were performed together with fasting blood sampling and anthropometric measurements. Insulin sensitivity measured by SSPG was estimated as glucose clearance corrected by the excretion of glucose into urine (C-GC). Results: Log-transformed (C-GC) was negatively correlated with fasting plasma glucose (FPG), log (Fasting triglyceride: TG), log (Fasting TG/Fasting high-density lipoprotein cholesterol: HDLC), and their area under the curves (AUCs). Fasting and AUC-HDLC was positively and fasting free fatty acid (FFA) was negatively correlated with log (C-GC). Body fat (%) was negatively correlated with log (C-GC). Multiple regression analysis on log (C-GC) as an outcome variable revealed that FPG, log (AUC-TG/AUC-HDLC), body fat (%), and fasting FFA were selected as significant predictive variables and contributed to log (C-GC) by 60% (adjusted R 2 ). Replacing log (AUC-TG/AUC-HDLC) with its fasting value, log (Fasting TG/Fasting HDLC), this model still showed a strong contribution to log (C-GC) by 57% (adjusted R 2 ). These contributions were stronger than those in log (HOMA-IR) (52.5%), log (Fasting C-peptide) (45.7%) to log (C-GC). Conclusions: It is plausible that our estimation for IR without the inclusion of plasma insulin concentration can be applied in Japanese patients whose HOMA-IR is not appropriately available. The model using fasting values is less complicated and could be the best way for the estimation of IR.

Background Chronic inflammation and insulin resistance are factors that are related to obesity. We have suggested that the administration of heat-treated Lactobacillus plantarum OLL2712 (OLL2712) cells can improve glucose and lipid metabolism by suppressing chronic inflammation in mouse models and a preliminary clinical study. Objective The aim of this study was to investigate whether ingesting OLL2712 cells can reduce body fat accumulation and improve metabolic risk factors, in overweight, healthy adults. Methods This study was a randomized, double-blind, placebo-controlled, parallel-group trial conducted at a single center in Japan. The study participants included 100 overweight (BMI range, ≥25 to <30 kg/m2) adults aged 20–64 y. They were randomly assigned to either the placebo or OLL2712 group (n  = 50 each) and were administered conventional yogurt or yogurt containing >5 × 109 heat-treated OLL2712 cells, respectively, daily for 12 wk. The primary outcome was the 12-wk change in the abdominal fat area, as assessed by computed tomography, and the secondary outcomes were glucose and lipid metabolism-related parameters and chronic inflammation markers, which were analyzed using a linear mixed model. Results The 12-wk change of abdominal fat area (difference: 8.5 cm2; 95% CI: 0.3, 16.6 cm2; P  = 0.040) and fasting plasma glucose (difference: 3.2 mg/dL; 95% CI: 0.8, 5.6 mg/dL; P  = 0.021) were significantly less in the OLL2712 group than the placebo group. The overall trend of serum IL-6 was significantly decreased in the OLL2712 group compared with baseline and the placebo group. Conclusions The ingestion of heat-treated OLL2712 cells reduces body fat accumulation and the deterioration of glycemic control and chronic inflammation, in overweight, healthy adults. We hypothesize that OLL2712 cells may prevent obesity by regulating chronic inflammation. This trial was registered at the University Hospital Medical Information Network Clinical Trials Registry as UMIN000027709. [ABSTRACT FROM AUTHOR]

Background: It is unclear whether light physical activity is beneficially associated with insulin resistance, similar to moderate and/or vigorous physical activity. This cross-sectional study was performed to determine the relationship between the amount of light physical activity, as determined with a triaxial accelerometer, and insulin resistance. Methods: A total of 807 healthy men and women participated in this study. Physical activity was measured using a triaxial accelerometer worn for 28 days and summarized as light intensity (1.1-2.9 METs) or moderate to vigorous intensity (= 3.0 METs). Insulin resistance was evaluated by HOMA_R (FPG [mg/dL] x IRI [µU/mL]/405). Results: The daily time spent in light physical activity was inversely associated with HOMA_R (r = -0.173, P < 0.05). After adjustment for confounders, the association between light physical activity and HOMA_R remained statistically significant (β = -0.119, P < .05). Light physical activity remained significantly associated with HOMA_R following further adjustment for moderate to vigorous intensity activity (β = -0.125, P < .05). Similar results were observed when light physical activity was modeled as quartiles, especially in elderly women. Conclusions: These cross-sectional data suggest that light-intensity physical activity is beneficially associated with insulin resistance in elderly Japanese women. [ABSTRACT FROM AUTHOR]

Aims: The present study aimed to clarify the relationships between novel and traditional anthropometric indices and insulin sensitivity (SI) in young and middle-aged Japanese persons with normal glucose tolerance (NGT), and middle-aged Japanese persons with NGT and glucose intolerance. Methods: Plasma glucose and insulin levels were measured in 1270 young (age <40 years) and 2153 middle-aged persons with NGT ( n  = 1531) and glucose intolerance ( n  = 622) during a 75-g oral glucose tolerance test. Height (Ht), weight, and waist circumference (WC) were measured. The body mass index (BMI), WC, and the WC/Ht ratio were used as traditional anthropometric indices. A body shape index (ABSI) and the body roundness index (BRI) were calculated as novel indices. Indices of SI (Matsuda index and 1/homeostasis model assessment of insulin resistance) were calculated and compared with anthropometric indices. Results: The ABSI showed a weak correlation with SI indices in all groups. The BRI showed almost the same correlation with SI indices as the BMI, WC, and WC/Ht in all groups. The inverse correlation between each of the anthropometric indices other than ABSI and SI indices was weak in young persons, at 0.16-0.27 (Spearman's ρ values), but strong in middle-aged persons, at 0.38-1.00. On receiver-operating characteristic (ROC) curve analysis for detection of insulin resistance, the ABSI had a lower area under the ROC curve (AUC) than the other anthropometric indices, and the BRI and the WC/Ht ratio showed similar AUCs. The AUCs for the BRI and WC/Ht ratio were the highest in middle-aged men with NGT and glucose intolerance. Conclusions: The BRI, not the ABSI, was better correlated with SI in young and middle-aged Japanese persons. The BRI and WC/Ht ratio were comparable in their correlations with SI and the detection of insulin resistance in the participants of the present study.

Background: Body mass index (BMI) and fasting plasma glucose (FPG) are known risk factors for type 2 diabetes mellitus (T2DM), but data on the prospective association of the combination of BMI and FPG with T2DM are limited. This study sought to characterize the association of the combination of BMI and FPG (ByG) with T2DM., Methods: The current study used the NAGALA database. We categorized participants by tertiles of ByG. The association of ByG with T2DM was expressed with hazard ratios (HRs) with 95% confidence intervals (CIs) after adjustment for potential risk factors., Results: During a median follow-up of 6.19 years in the normoglycemia cohort and 5.58 years in the prediabetes cohort, the incidence of T2DM was 0.75% and 7.79%, respectively. Following multivariable adjustments, there were stepwise increases in T2DM with increasing tertiles of ByG. After a similar multivariable adjustment, the risk of T2DM was 2.57 (95% CI 2.26 - 2.92), 1.97 (95% CI 1.53 - 2.54) and 1.50 (95% CI 1.30 - 1.74) for a per-SD change in ByG in all populations, the normoglycemia cohort and the prediabetes cohort, respectively., Conclusion: ByG was associated with an increased risk of T2DM in Japan. The result reinforced the importance of the combination of BMI and FPG in assessing T2DM risk., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhao, Yao, Song, Fan, Liu, Gao, Wang, Lu and Liu.)

Background: The association between chronic lipopolysaccharide exposure and the development of metabolic syndrome (MetS) is unclear. In this study we examined the association between serum lipopolysaccharide-binding protein (LBP) levels, an indicator of lipopolysaccharide exposure, and the development of MetS in a general Japanese population., Methods: 1,869 community-dwelling Japanese individuals aged ≥40 years without MetS at baseline examination in 2002-2003 were followed up by repeated examination in 2007-2008. MetS was defined according to the Japanese criteria. Serum LBP levels were classified into quartiles (quartiles 1-4: 2.20-9.56, 9.57-10.78, 10.79-12.18, and 12.19-24.34 µg/mL, respectively). Odds ratios (ORs) for developing MetS were calculated using a logistic regression model., Results: At the follow-up survey, 159 participants had developed MetS. Higher serum LBP levels were associated with greater risk of developing MetS after multivariable adjustment for age, sex, smoking, drinking, and exercise habits (OR [95% confidence interval] for quartiles 1-4: 1.00 [reference], 2.92 [1.59-5.37], 3.48 [1.91-6.35], and 3.86 [2.12-7.03], respectively; P for trend <0.001). After additional adjustment for homeostasis model assessment of insulin resistance, this association was attenuated but remained significant (P for trend = 0.007). On the other hand, no significant association was observed after additional adjustment for serum high-sensitivity C-reactive protein (P for trend = 0.07)., Conclusion: In the general Japanese population, our findings suggest that higher serum LBP levels are associated with elevated risk of developing MetS. Low-grade endotoxemia could play a role in the development of MetS through systemic chronic inflammation and insulin resistance.

Aim: This study examined the association between the metabolic score for insulin resistance (METS-IR), a novel surrogate indicator of insulin resistance, and brachial-ankle pulse wave velocity (baPWV) in Japanese health check participants., Methods: A cross-sectional research was conducted involving individuals in a program of medical health screening at the Medical Health Check-up Center in Japan. The study assessed the connection between METS-IR and baPWV in 912 participants who joined the program between 3/1/2004 and 12/31/2012. Serum laboratory tests and lifestyle surveys were the covariates. Multivariate linear regression analysis and subgroup analyses were performed., Results: 912 participants were involved in this cross-sectional study. Adjusted for age, sex, BMI, AST, UA, HDL, eGFR, ankle-brachial index (ABI), alcohol consumption, and smoking status, multivariate linear regression analysis showed that METS-IR and baPWV showed a significant positive association (adjusted β=15.3, 95% confidence interval (CI): 6.61~23.98) with METS-IR as a continuous variable. When converting METS-IR to quartile categorical variables, higher quartile METS-IR indices had longer baPWV (Q3 vs Q1, β=86.14, 95% CI: 23.45~148.83; Q4 vs Q1, β=125.41, 95% CI: 39.99~210.84). In subgroup analysis, METS-IR was associated with baPWV in people with eGFR > 60 ml/min (adjusted β= 14.44, 95% CI: 5.61~23.26, P=0.001), none or light alcohol consumption (adjusted β=16.92, 95% CI: 6.85~27, P=0.001), non-smokers (adjusted β=15.48, 95% CI: 5.86~25.1, P=0.002), non-regular exercisers(adjusted β=17.34, 95% CI: 8.03~26.65, P<0.001), non-fatty liver (adjusted β=17.65, 95% CI: 5.92~29.39, P=0.003), and non-hypertensive (adjusted β=16.13, 95% CI:8.45~23.8, P<0.001)., Conclusion: METS-IR are remarkably associated with baPWV among health check-up participants in Gifu, Japan. As a simple, easily calculated predictor of arterial stiffness, METS-IR could be considered for primary care as a monitoring tool to identify people with high risk of cardiovascular disease in order to intervene early on risk factors. Future prospective, large-sample researches are still needed to confirm this., Competing Interests: The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Liu.)

Objectives: This study aims to evaluate the endocrine differences among polycystic ovary syndrome (PCOS) phenotypes in Japanese women., Methods: 118 Japanese women that we diagnosed with PCOS agreed to be included in the study. The study group was classified into the following 4 phenotypes: (A) hyperandrogenism (HA); ovulatory disorder (OvD) and polycystic ovary morphology (PCOM); (B) HA and OvD; (C) HA and PCOM; and (D) OvD and PCOM. We also recruited 66 healthy Japanese women to the study as control participants. Age, body mass index, androgens, luteinizing hormone, follicle-stimulating hormone, and insulin resistance (IR) index were evaluated and compared., Results: The proportions of phenotypes A, B, C, and D were 57/120 (47.5%), 4/120 (3.3%), 13/120 (10.8%), and 46/120 (38.3%), respectively. The proportion of phenotype B was too small; therefore, phenotypes A and B were grouped as classical PCOS for intergroup comparisons. The luteinizing hormone/follicle-stimulating hormone ratio in the classical PCOS group was higher than that in the phenotype D group (P < 0.001). Androgen concentrations in the phenotype D group were significantly lower than those in the other groups (P < 0.01). Phenotype D was more common in lean women with PCOS. The surrogate marker of IR (homeostasis model assessment of IR) was not different irrespective of PCOS and its phenotypes., Conclusions: Except for androgens, endocrine differences by PCOS phenotype are not evident, suggesting that diversity among patients with PCOS is relatively low in Japanese women., (Copyright © 2023 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. Published by Elsevier Inc. All rights reserved.)

Aims: To determine the prevalence and severity of endocrine and metabolic derangements in childhood-onset ALL survivors from Thailand and to describe the associated risk factors. Settings and Design: Paediatric department in medical school hospital, cross-sectional study. Methods: Insulin Tolerance Test (ITT), IGF-I and IGFBP-3 levels, Thyroid and gonadal function, serum sodium and metabolic profiles were investigated in 30 childhood onset ALL survivors. (16 males, 14 females, mean age: 14.66 ± 7.16 years). Results: Endocrine abnormalities were displayed in 73.33% of patients, 46.7% had two or more abnormalities. Grade3 of severity were present in 16.67%. Growth hormone deficiency (GHD) was detected in 10 patients (33%). Early onset of ALL was the potential risk factor of GHD. Adult height was more deteriorated in the female group. Twenty percent of patients were found with subnormal cortisol responses. Gonadal failure was evidenced in one case that experienced testicular irradiation. No diabetes insipidus was detected. Among 6 obese patients, 2 patients developed metabolic syndrome. Moreover, one patient was diagnosed with insulin-depleted diabetes mellitus. Conclusion: Our results highlighted various endocrine and metabolic sequelae occurring in childhood-onset ALL survivors after completion of their therapy. The prevalence of GHD was higher than the one previously described in Japan population. Subclinical hormonal abnormalities may affect health outcomes. Biochemical and hormonal abnormalities should be carefully monitored for immediate treatment. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer (CRC), which is related with insulin resistance, is a one of the most common cancers. Triglyceride-glucose index (TyG index) was made for a marker of insulin resistance. We conducted the investigation of association between TyG index and incident CRC. Methods: We examined the affect of TyG index on incident CRC in this historical cohort study of 27,944 (16,454 men and 11,490 women) participants. TyG index was calculated as ln [fasting triglycerides (mg/dL) × fasting plasma glucose (mg/dL)/2]. The impact of TyG index on incident CRC was investigated using Cox proportional hazard models, adjusting for sex, age, body mass index, smoking status, alcohol consumption, exercise, systolic blood pressure and creatinine. The covariate-adjusted receiver operating characteristic (ROC) curve calculated the area under the curve (AUC) and cut-off value of TyG index for the incidence of CRC. Results: During the median 4.4-year follow-up, 116 participants were diagnosed as CRC. The cumulative incidence rate of CRC were 0.4%. In Cox proportional hazard model, the HRs of TyG index were 1.38 (95% Confidence interval (CI), 1.00–1.91, p = 0.049) after adjusting for covariates. In the covariate-adjusted ROC curve analysis, the cut-off value of TyG index for incident CRC was 8.272 (AUC 0.687 (95%CI, 0.637–737, sensitivity = 0.620, specificity = 0.668, p < 0.001)). Conclusions: TyG index can predict the onset of CRC. For early detection of CRC, we should encourage people with high TyG index to undergo screening for CRC. [ABSTRACT FROM AUTHOR]

Triglyceride (TG) is a tri-ester composed of a glycerol and 3 fatty acids. Degradation of TG in adipose tissue is increased in the fasting state but inhibited in the postprandial state. Although insulin suppresses adipose TG degradation, patients with insulin resistance have high concentrations of insulin and free glycerol (FG) in the fasting state. We examined whether the fasting FG concentration reflects visceral obesity and insulin sensitivity in middle-aged Japanese men. We measured the fasting serum FG concentration in 72 males aged 30 to 50 years using a simple enzymatic method. The subjects were divided into tertiles according to their homeostasis model assessment of insulin resistance (HOMA-IR). Besides routine glucose- and lipid-related parameters, we determined insulin sensitivity as the rate of glucose disappearance in a 2-step hyperinsulinemic-euglycemic clamp and the abdominal visceral fat area (VFA) by magnetic resonance imaging. The highest HOMA-IR tertile group had a higher fasting FG concentration than the middle- and lowest-tertile groups (0.077 ± 0.024 vs 0.063 ± 0.017 and 0.061 ± 0.016 mmol/L, P <.05 and P <.01). The FG concentration was positively correlated with VFA (rs = 0.36; P <.01) and the HOMA-IR score (rs = 0.26, P <.05) but negatively correlated with insulin sensitivity (rs = −0.26, P <.05). Multivariate regression analysis revealed that the FG concentration is independently associated with VFA and insulin sensitivity. The fasting FG concentration reflects VFA and insulin sensitivity in middle-aged Japanese men. The fasting FG concentration may be a potential surrogate marker of visceral obesity and insulin resistance in outpatients. • We measured the fasting free glycerol (FG) levels in 72 middle-aged Japanese men. • The fasting FG level was positively correlated with visceral fat area. • The fasting FG level was negatively correlated with insulin sensitivity. • The fasting FG concentration reflects visceral obesity and insulin resistance. • The fasting FG level may be a surrogate marker of visceral fat area and insulin resistance. [ABSTRACT FROM AUTHOR]

Background: Sleep deprivation and circadian disruption are associated with decreased insulin sensitivity and hyperglycemia. It is uncertain whether circadian sleep‐wake disorder (CRSWD), which relates to both the homeostatic sleep system and the circadian timing system, affects glycemic regulation and insulin secretion. We aimed to examine the associations among sleep duration, sleep architecture or circadian rhythm of the sleep‐wake cycle, and glucose metabolism in children, adolescents, and young adults with CRSWD. Methods: This cross‐sectional observational study of 124 patients with CRSWD took place at Hyogo Children's Sleep and Development Medical Research Center in Hyogo, Japan. The patients underwent a 3‐hour oral glucose tolerance test, anthropometric measurements, sleep‐log analyses, and polysomnography. Analysis of covariance models were used to assess the association between sleep architecture or circadian rhythm of sleep‐wake cycle and glucose/insulin homeostasis, adjusted for confounding variables such as age, gender, standardized body mass index, and sleep apnea index. Results: Impaired glucose tolerance was detected in 25.8% of all patients with CRSWD. After adjustment for confounding variables, we found a negative association between total sleep time (TST) and the 2‐hour plasma glucose level. Stage N1 (%TST) was also a significant predictor of 3‐hour glucose level. However, we did not detect an association between circadian rhythm of the sleep‐wake cycle and glucose/insulin measures. Conclusions: Decreased sleep duration and increased stage N1 (%TST) were associated with hyperglycemia in patients with CRSWD. Further research should elucidate how circadian misalignment in patients with CRSWD is associated with glucose and insulin homeostasis. [ABSTRACT FROM AUTHOR]

Introduction: EMOTION was a multinational, noninterventional study surveying current insulin-using adults with type 2 diabetes mellitus (T2D) who were initially reluctant to begin insulin treatment. In this Japanese population subanalysis of EMOTION, we identify the frequency and level of helpfulness of healthcare provider (HCP) actions, and we analyze life events ('actions/events') that assist T2D patients with psychological insulin resistance in the decision to initiate insulin. Methods: Participants were selected from Survey Sampling International and their local partners' market research panels in Japan. Quantitative surveys were administered between December 2016 and August 2017 to patients who met the study criteria. Participants were asked whether 45 actions/events occurred, and to rate the level of helpfulness of the actions/events in contributing to their decision to initiate insulin. Results: Among the 594 eligible participating adults in the EMOTION study, 99 were from Japan. Despite initial reluctance to begin insulin treatment, 80.8% of the Japanese participants immediately commenced insulin. Practical demonstrations by HCPs on how to use insulin were rated by participants as most helpful. Examples of such practical demonstrations, reported as helping moderately or a lot, were 'HCP walked patient through the process of exactly how to take insulin' (82.8%), 'HCP showed an insulin pen' (79.7%), and 'HCP helped patient to see how simple it was to inject insulin' (79.1%). Conclusion: This study identifies actions that HCPs can use to assist Japanese patients in deciding whether to initiate insulin. These findings may aid the development of clinical interventions addressing reluctance to begin insulin treatment among Japanese patients with T2D. Funding: Eli Lilly and Company and Boehringer Ingelheim. Plain Language Summary: Plain language summary available for this article. Plain Language Summary: The increasing prevalence of type 2 diabetes mellitus (T2D) is a major health concern globally. In Japan, the prevalence of diabetes is predicted to increase over the next decades. Insulin is a hormone which keeps blood glucose levels within the normal range. People with diabetes often require insulin therapy as they do not make sufficient insulin, or the insulin that is produced does not work optimally. Many patients delay insulin therapy due to a variety of factors. Reluctance to begin insulin treatment is known as 'psychological insulin resistance' (PIR). Several studies have described recommendations to address PIR, but there is little research regarding effective strategies that help reluctant patients begin insulin. Reports describing PIR among Japanese patients are limited. EMOTION was a multinational study surveying insulin-using adults with T2D and initial PIR. We report a Japanese population subanalysis of EMOTION, identifying factors which help reluctant Japanese patients begin insulin therapy. Our results indicate that healthcare provider (HCP) actions are associated with a patient's decision to use insulin. Practical demonstrations by HCPs on how to use insulin were reported as most helpful. Reassurance concerning pain of injection, explanations regarding blood glucose numbers and future health, encouragement to make contact in case of any problems, and occurrence of a positive life event were also rated by Japanese participants as being helpful in deciding to commence insulin. This study provides important information on actions that can be used by HCPs to treat Japanese patients with T2D who are reluctant to begin insulin treatment. [ABSTRACT FROM AUTHOR]

Introduction: Insulin is synthesized in the β-cells from preproinsulin. Preproinsulin becomes proinsulin after leaving the signal peptide. Proinsulin is separated into C-peptide and insulin by 2 enzymes. Hyperproinsulinemia is suspected to be a pancreatic β-cell defect that is augmented by the increased demand placed on the β-cell by hyperglycemia. Case presentation: A 39-year-old Japanese man visited to Shin-suma hospital in May 2013. Liver dysfunction, dyslipidemia, and hyperuricemia had been found in medical checkups in his workplace. Therefore, he visited Shin-suma hospital in order to receive intensive examination. Diet and exercise therapy were initiated. In November 2013, intact proinsulin and proinsulin per insulin (PI/I) ratio were evaluated as part of an ongoing study. His intact proinsulin level and PI/I ratio were markedly elevated. A 75 g oral OGTT revealed that his glucose tolerance was impaired. His glycosylated hemoglobin was 6.9%. He was diagnosed as having type 2 diabetes mellitus. Although, diet and exercise therapy continued, his hyperproinslinemia and diabetes mellitus remained. Therefore, aloguliptin was started in order to recover insulin secretion in November 2014. Thereafter, pioglitazone was added to improve insulin resistance. Finally, luseogliflozin was commenced to expect glucose-lowering effects. His HbA1c was stabilized. To the best of our knowledge, there have been few reports of patients with hyperproinsulinemia. Conclusion: When the physicians face treatment resistance in diabetes mellitus, we emphasize that evaluation of proinsulin should be considered as one of the methods. [ABSTRACT FROM AUTHOR]

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/m 2 , respectively. Results: On multivariate linear regression analysis in young women, ALT/AST was associated with trunk/leg fat ratio (standardized β  = 0.202, P  = 0.007), a marker of abdominal fat accumulation, and AT-IR (standardized β  = 0.185, P  = 0.003) independently of HOMA-IR and Matsuda index ( R 2  = 0.07). In middle-aged women, leptin/adiponectin ratio (standardized β  = 0.446, P  < 0.001) and AT-IR (standardized β  = 0.292, P  = 0.009) emerged as determinants of ALT/AST independently of trunk/leg fat ratio, OGTT-derived hepatic IR, leptin, and adiponectin ( R 2  = 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.

Aim. To identify the involvement of leanness and impaired insulin secretion with Japanese gestational diabetes mellitus (GDM). Method. A cross-sectional study was conducted comprising 219 at-risk pregnant women who underwent a 75g glucose tolerance test at a single institute in Tokyo, Japan. We identified GDM and normal glucose tolerance (NGT). The cut-off value of the homeostasis model assessment insulin resistance (HOMA-IR) for detecting GDM was determined. The GDM group was divided into subgroups according to insulin resistance based on the cut-off value of HOMA-IR. We compared the prepregnancy body mass index (BMI) and homeostasis model assessment of β-cell function (HOMA-β) between the group comprising low insulin resistance (LIR) and the group comprising high insulin resistance (HIR). Results. Seventy GDM cases and 149 NGT cases were identified. By using receiver operating characteristic curve analysis, the HOMA-IR cut-off value was determined to be 1.41. Twenty-five GDM cases (36%) were classified as LIR and forty-five GDM cases (64%) were classified as HIR. The background including indications for having 75gOGTT and the gestational age having 75gOGTT did not differ between groups. The BMI of the LIR group was significantly lower than that of the HIR group (20.9±2.8 vs. 24.4 ± 5.5, p<0.01), and the HOMA-β of the LIR group was significantly lower than that of the HIR group (95.5±30.3 vs. 146.0±70.1, p<0.01). A positive linear correlation was found between BMI and HOMA-β in cases of GDM (r=0.27, p=0.02). Conclusion. Leanness with impaired insulin secretion is deeply involved in Japanese gestational diabetes mellitus. [ABSTRACT FROM AUTHOR]

Objective. The number of patients with type 2 diabetes has increased in Japan, and type 2 diabetes has attracted attention as a risk factor for asthma. However, the risk factors for the development of asthma in patients with type 2 diabetes have not been determined. This study was performed to clarify whether visceral fat accumulation (VFA) and insulin resistance are risk factors for the development of asthma in patients with type 2 diabetes. Materials and Methods. A cross-sectional study was conducted. The study group comprised 15 patients with type 2 diabetes with asthma, and the control group comprised 145 patients with type 2 diabetes without asthma. Their fat distribution was evaluated by measuring the VFA by abdominal computed tomography at the umbilical level. Their glucose status was assessed by measuring the fasting plasma glucose (FPG) concentration, fasting immunoreactive insulin concentration, homeostasis model assessment (HOMA) index, and hemoglobin A1c concentration. Results. Among patients with type 2 diabetes, VFA was significantly greater in patients with asthma than those without asthma (P<0.0001). The FPG concentration, fasting immunoreactive insulin concentration, and HOMA index were higher in patients with asthma than those without asthma (P<0.05, P<0.0001, and P<0.0001, respectively). Multiple logistic regression analysis showed that VFA and the HOMA index were significantly associated with asthma in patients with type 2 diabetes (odds ratio, 1.78; 95% confidence interval, 1.31–3.89; P=0.0115 and odds ratio, 3.65; 95% confidence interval, 1.37–7.85; P=0.0078, respectively). Conclusions. Our data suggest that VFA and insulin resistance are associated with the development of asthma in patients with type 2 diabetes. [ABSTRACT FROM AUTHOR]

Background: Based on non-clinical data, it is expected that azilsartan, an angiotensin II receptor blocker, will help improve insulin resistance in addition to its hypotensive action. The present study is aimed to explore the effect of azilsartan compared to telmisartan on insulin sensitivity in hypertensive patients in the clinical setting. Methods: This multicenter, randomized, open-label, parallel-group exploratory study was conducted in Japan. We randomized adult patients (≥20 years old) with grade I or II essential hypertension and coexisting type 2 diabetes (1:1) to receive either oral azilsartan (20 mg/day;17 patients) or telmisartan (40 mg/day;16 patients) for 12 weeks. The primary endpoint was the change in the homeostasis model assessment ratio of insulin resistance (HOMA-R) from the baseline at the end of the treatment period. We also evaluated its safety and efficacy on other diabetes-related variables and blood pressure. Findings: The mean changes in HOMA-R at the end of treatment were 0.22 (95% CI, −1.09–1.52) in the azilsartan group and −0.23 (95% CI, −0.72–0.27) in the telmisartan group. We found no clinically remarkable changes between the groups in diabetes-related variables such as fasting blood glucose, fasting insulin, HbA1c (NGSP), HOMA-β, or 1,5-anhydroglucitol. Reductions in clinic systolic and diastolic blood pressure were observed at week 4 and the reduced levels were maintained throughout the treatment period in both groups. No serious treatment-emergent adverse events (TEAEs) were observed. Only one drug-related TEAE (mild decrease in blood pressure) was reported in one patient in the azilsartan group. Conclusion: Neither azilsartan nor telmisartan had any clinically remarkable effects on insulin resistance parameters when administered for 12 weeks to patients with grade I or II essential hypertension and coexisting type 2 diabetes mellitus. Azilsartan (20 mg/day) and telmisartan (40 mg/day) exerted comparable antihypertensive effects. Trial registration: ClinicalTrials.gov [ABSTRACT FROM AUTHOR]

Aims: Information on the clinical efficacy of SGLT2 inhibitors in the Japanese population is limited. The aim of this single-arm, single-center, open-label study was to confirm the body weight- and fat mass-lowering effects of canagliflozin (CANA) and the accompanying improvement in insulin resistance in Japanese patients with Type 2 diabetes mellitus (T2DM).Methods: Thirty-eight patients were enrolled and administered 100 mg CANA once daily for 24 weeks. Blood and anthropometric parameters were examined before and after treatment. In a subset of patients, insulin sensitivity was assessed based on the glucose infusion rate (GIR) during a hyperinsulinemic euglycemic clamp test.Results: CANA treatment significantly decreased hemoglobin A1c, fasting plasma glucose, and plasma liver enzyme levels, and increased plasma adiponectin levels. In addition, a significant reduction in body weight, visceral and subcutaneous fat area, fat and lean mass, and liver steatosis was also observed. The change in plasma adiponectin levels significantly correlated with the changes in both body fat mass and visceral fat area. GIR increased from 3.25 ± 1.53 to 4.11 ± 1.30 mg/kg/min (P < 0.05).Conclusions: CANA improved insulin resistance and decreased visceral fat mass in Japanese patients with T2DM. [ABSTRACT FROM AUTHOR]

Background: Causative mutations cannot be identified in the majority of Asian patients with suspected maturity‐onset diabetes of the young (MODY). Objectives: To elucidate the genetic basis of Japanese patients with MODY‐like diabetes and gain insight into the etiology of patients without mutations in the major MODY genes. Subjects A total of 263 Japanese patients with early‐onset, non‐obese, MODY‐like diabetes mellitus referred to Osaka City General Hospital for diagnosis. Methods: Mutational analysis of the four major MODY genes (GCK, HNF1A, HNF4A, HNF1B) by Sanger sequencing. Mutation‐positive and mutation‐negative patients were further analyzed for clinical features. Results: Mutations were identified in 103 (39.2%) patients; 57 mutations in GCK; 29, HNF1A; 7, HNF4A; and 10, HNF1B. Contrary to conventional diagnostic criteria, 18.4% of mutation‐positive patients did not have affected parents and 8.2% were in the overweight range (body mass index [BMI] >85th percentile). HOMA‐IR at diagnosis was elevated (>2) in 15 of 66 (22.7%) mutation‐positive patients. Compared with mutation‐positive patients, mutation‐negative patients were significantly older (P = 0.003), and had higher BMI percentile at diagnosis (P = 0.0006). Interestingly, maternal inheritance of diabetes was significantly more common in mutation‐negative patients (P = 0.0332) and these patients had significantly higher BMI percentile as compared with mutation‐negative patients with paternal inheritance (P = 0.0106). Conclusions: Contrary to the conventional diagnostic criteria, de novo diabetes, overweight, and insulin‐resistance are common in Japanese patients with mutation‐positive MODY. A significant fraction of mutation‐negative patients had features of early‐onset type 2 diabetes common in Japanese, and non‐Mendelian inheritance needs to be considered for these patients. [ABSTRACT FROM AUTHOR]

The bibliometric analysis assesses the productivity of scholarship in a given field and provides information on the frontiers of relevant developments. However, no bibliometric analysis study has quantitatively analyzed publications in geriatric sarcopenia therapies. This study investigates the scholarly productivity and frontiers of publications in geriatric sarcopenia therapies. The bibliometric data came from English-language Web of Science Core Collection articles published between 1995 and October 19, 2022. Three software programs, R version 3.5.6, VOSviewer, and CiteSpace, were applied for this bibliometric analysis. In twenty-eight years, the annual publications in geriatric sarcopenia therapies have increased yearly, with an annual growth rate of 21.23 %. A total of 1379 publications have been published. The United States was the country with the highest number of publication signatures (n=1,537) (including joint publication releases), followed by Japan (n=1099). Journal of Cachexia, Sarcopenia, and Muscle contributed the best journal publications (n=80). The newest hot subjects in the study about geriatric sarcopenia therapy include malnutrition, obesity, insulin resistance, and cancer. This bibliometric study presents a comprehensive overview of the current and future research directions in geriatric sarcopenia therapies over the past 28 years. Overall, this study has complemented the gaps in bibliometric analysis in geriatric sarcopenia therapies. This paper will provide a valuable reference for future research in geriatric sarcopenia therapies., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2023 The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.)

Purpose It has been demonstrated that circulating microRNA profiles are affected by physiological conditions. Several studies have demonstrated that microRNAs play important roles in the regulation of adiposity. However, few have investigated the relationship between circulating microRNAs and obesity, which has become a major public health problem worldwide. This study investigated the association between circulating microRNAs and obesity in a Japanese population. Methods Obesity parameters, such as subcutaneous and visceral fat adipose tissue, body fat percentage, and body mass index were assessed in a cross-sectional sample of 526 participants who attended health examinations in Yakumo, Japan. In addition, five circulating microRNAs (miR-20a, -21, -27a, -103a, and -320), which are involved in adipocyte proliferation and differentiation, were quantified using real-time polymerase chain reaction amplification. Results We compared the circulating microRNA concentrations in a percentile greater than 75th (high) with below the value (low) of subcutaneous adipose tissue, visceral fat adipose tissue, body mass index, and per cent body fat. For visceral fat adipose tissue, significant decrease in miR-320 expression was observed in high group. Also, for body mass index, significant change of miR-20a, -27a, 103a, and 320 expression level was observed in high group. Multiple linear regression analysis demonstrated that circulating levels of some microRNA such as miR-27a were significantly associated with subcutaneous adipose tissue, visceral fat adipose tissue, and body mass index. Conclusions Our findings support the need for further studies to determine whether such changes are consistent across different populations and whether the identified microRNAs may represent novel biomarkers to predict the susceptibility and progression of obesity-related disorders. [ABSTRACT FROM AUTHOR]

Levels of isoflavones, biomarkers of soy intake, in 24-hour urine (24U) were inversely related to coronary heart disease (CHD) mortality in the World Health Organization's Cardiovascular Disease and Alimentary Comparison Study. Considering 24U isoflavone levels were highest and CHD mortality was lowest in the Japanese, who maintained the world's longest life expectancy, the association of regular soy intake with cardiometabolic risk was investigated in Japanese adults (20-49 years old) and elderly (50-79 years old). In multivariate analysis adjusted for age, sex, and drug treatments, mean 24U isoflavone excretion was significantly inversely associated with insulin resistance in the elderly and significantly associated with blood folate and potassium in the elderly, but also positively associated with 24U salt in the elderly. These findings indicate that low-salt soy should be recommended to improve glucose metabolism in elderly Japanese. [ABSTRACT FROM AUTHOR]

Aim: Physical activity (PA) and cognition have reportedly been associated with each other. However, it remains to be elucidated what intensities of PA are most strongly associated with cognition. In the current study, we aimed to determine the association between the intensities of objectively measured PA and cognitive function. Methods: The present study was a cross‐sectional analysis of the data obtained at registration in a randomized control trial in Toyota, Japan. Participants were community‐dwelling older adults who had cognitive complaints. A battery of neuropsychological and physical assessments was carried out. Daily PA data were collected with the activity monitor. PA was categorized into one of three activity levels defined as light (<3.0 metabolic equivalents; LPA), moderate and vigorous (3.0 metabolic equivalents) activity. Partial correlation analysis was used to investigate the correlation between PA and cognition, with adjustments for age, sex and school years. We then carried out a multiple regression analysis to investigate the association of cognitive performance with PA, adjusting for insulin resistance or depressive mood. Results: Partial correlation adjusted for age, sex and schooling years showed that LPA was significantly correlated with the Digit Symbol Substitution test, Trail Making Test (TMT) part A and TMT‐B, whereas moderate and vigorous activity showed no correlations. Multiple regression analysis with several models with different adjustments showed that LPA was associated with the Digit Symbol Substitution test, TMT‐A and TMT‐B independently from insulin resistance or depressive mood. Conclusions: In the current study, we found that LPA was significantly associated with the performance of executive functional assessments. Geriatr Gerontol Int 2018; 18: 922–928. [ABSTRACT FROM AUTHOR]

An easily understandable index that measures the quality of carbohydrate may aid people in adopting dietary habits that improve their glucose tolerance. We aimed to evaluate the relationship between a ratio of dietary fibre to carbohydrate intakes (fibre:carbohydrate ratio (F:C-R)) and glucose tolerance cross-sectionally and longitudinally. Subjects were 190 Japanese men and women without type 2 diabetes (mean age 55·4 years) who participated in a 5-month diet and exercise programme. We compared baseline anthropometric, dietary and metabolic profiles between those with higher F:C-R and those with lower ratios. Multivariable regression analyses were performed to examine the associations between the F:C-R and homoeostasis model of assessment for insulin resistance (HOMA-IR) and HbA1c at baseline and between changes in the F:C-R and changes in HOMA-IR and HbA1c over the 5-month period. At baseline, the higher F:C-R group had significantly lower body weight, lean body mass, fasting insulin level and HOMA-IR as compared with the lower F:C-R group. The two groups had similar intakes of carbohydrate and fat, whereas protein intake was greater in the high F:C-R group. Baseline F:C-R was not significantly associated with HOMA-IR or HbA1c at the beginning of the study in multivariable models. Increases in the ratio during the 5-month programme was associated with reductions in HbA1c (P<0·001). These findings highlight the potential utility of the F:C-R in strategies aimed at type 2 diabetes prevention. [ABSTRACT FROM AUTHOR]