Imeglimin profoundly affects the circadian clock in mouse embryonic fibroblasts.

OBJECTIVE: Imeglimin is a novel antidiabetic drug structurally related to metformin. Metformin has been shown to modulate the circadian clock in rat fibroblasts. Accordingly, in the present study, we aimed to determine whether imeglimin can impact the circadian oscillator in mouse embryonic fibroblasts (MEFs). METHODS: MEFs carrying a Bmal1-Emerald luciferase (Bmal1-ELuc) reporter were exposed to imeglimin (0.1 or 1 mM), metformin (0.1 or 1 mM), a nicotinamide phosphoribosyltransferase inhibitor FK866, and/or vehicle. Subsequently, Bmal1-ELuc expression and clock gene mRNA expression levels were measured at 10-min intervals for 55 h and 4-h intervals for 32 h, respectively. RESULTS: Imeglimin significantly prolonged the period (from 26.3 to 30.0 h at 0.1 mM) and dose-dependently increased the amplitude (9.6-fold at 1 mM) of the Bmal1-ELuc expression rhythm; however, metformin exhibited minimal effects on these parameters. Moreover, imeglimin notably impacted the rhythmic mRNA expression of clock genes (Bmal1, Per1, and Cry1). The concurrent addition of FK866 partly inhibited the effects of imeglimin on both Bmal1-ELuc expression and clock gene mRNA expression. CONCLUSION: Collectively, these results reveal that imeglimin profoundly affects the circadian clock in MEFs. Further studies are needed to evaluate whether imeglimin treatment could exert similar effects in vivo.

Associations between dairy consumption and the physical function in Japanese community-dwelling older adults: The Shimane CoHRE study.

OBJECTIVES: We investigated sex differences in the associations between dairy consumption and the physical function among community-dwelling older adults. METHODS: Six hundred and fifty-six older adults (75.6 ± 6.4 years old) participated in this study. Dairy consumption (5-item Likert score) and the physical function (gait speed, handgrip strength, and skeletal muscle mass) were measured. The linear and quadratic associations between dairy consumption and the physical function measures were examined by a multiple linear regression analysis adjusted for covariates. RESULTS: Among women, an increased dairy consumption was significantly linearly associated with greater hand-grip strength and faster gait speed (both p<0.05) after adjusting for covariates. Among men, dairy consumption was not associated with the physical function measures. Dairy consumption was not associated with the muscle mass in either sex. CONCLUSIONS: Increased dairy consumption was associated with a superior physical function in older women.

Nutritional status in female patients with nontuberculous mycobacterial lung disease and its association with disease severity.

BACKGROUND: In women, slender body habitus has been reported to be one of the predisposing factors underlying the development and poor prognosis of non-tuberculous mycobacterial lung disease (NTM-LD). Given the lack of nutritional data contributing to treatment strategies, we aimed to clarify the nutritional status of female patients with NTM-LD and its association with disease severity. METHODS: In this single-center observational study, we enrolled 81 female outpatients with NTM-LD. Data on healthy women of similar ages were selected from our previous survey data and categorized as controls. First, we compared anthropometric and dietary survey data between patients and controls. Second, after the patients were categorized into relatively mild (mild, n = 40) and relatively severe groups (severe, n = 41) based on pulmonary X-ray-image finding scores, body composition, nutritional intake, and biochemical markers were compared between the groups. To identify nutritional factors associated with disease severity, logistic regression analyses were performed. RESULTS: Compared with controls, patients with NTM-LD had significantly lower energy intake, body mass index, body fat, and skeletal muscle mass (all p < 0.001). Compared with the mild group, the severe group had significantly lower skeletal muscle mass (p = 0.037), albumin (p = 0.029), transthyretin (prealbumin) (p = 0.002), retinol-binding protein (p = 0.011), and hemoglobin (p = 0.001); however, no between-group differences were observed in energy or nutrient intake. Logistic analyses revealed that transthyretin (p = 0.025) and hemoglobin (p = 0.003) levels were independent factors associated with disease severity. CONCLUSIONS: This is the first study to comprehensively report the association between NTM-LD severity and nutritional status, including body composition, nutrient intake, and biomarkers. The results suggest that initiating nutritional therapy from the mild stage of the disease to prevent undernutrition is warranted.

Diurnal variations of brown fat thermogenesis and fat oxidation in humans.

BACKGROUND/OBJECTIVES: Disturbed circadian rhythm is associated with an increased risk of obesity and metabolic disorders. Brown adipose tissue (BAT) is a site of nonshivering thermogenesis (NST) and plays a role in regulating whole-body energy expenditure (EE), substrate metabolism, and body fatness. In this study, we examined diurnal variations of NST in healthy humans by focusing on their relation to BAT activity. METHODS: Forty-four healthy men underwent 18F-fluoro-2-deoxy-D-glucose positron emission tomography and were divided into Low-BAT and High-BAT groups. In STUDY 1, EE, diet-induced thermogenesis (DIT), and fat oxidation (FO) were measured using a whole-room indirect calorimeter at 27 °C. In STUDY 2, EE, FO, and skin temperature in the region close to BAT depots (Tscv) and in the control region (Tc) were measured at 27 °C and after 90 min cold exposure at 19 °C in the morning and in the evening. RESULTS: In STUDY 1, DIT and FO after breakfast was higher in the High-BAT group than in the Low-BAT group (P < 0.05), whereas those after dinner were comparable in the two groups. FO in the High-BAT group was higher after breakfast than after dinner (P < 0.01). In STUDY 2, cold-induced increases in EE (CIT), FO, and Tscv relative to Tc in the morning were higher in the High-BAT group than in the Low-BAT group (P < 0.05), whereas those after dinner were comparable in the two groups. CIT in the High-BAT group tended to be higher in the morning than in the evening (P = 0.056). CONCLUSION: BAT-associated NST and FO were evident in the morning, but not in the evening, suggesting that the activity of human BAT is higher in the morning than in the evening, and thus may be involved in the association of an eating habit of breakfast skipping with obesity and related metabolic disorders.

Oral dryness and moisture degree at the lingual but not buccal mucosa predict prognosis in end-of-life cancer patients.

PURPOSE: The aim of this study is to investigate the association of oral dryness with overall survival and determine the threshold points of moisture degree for predicting 7-day survival in palliative care patients. METHODS: A total of 147 consecutive palliative care patients were included between January 2017 and November 2018. Oral dryness at the lingual and buccal mucosa was measured using an oral moisture-checking device. Overall survival was compared between patients with and without oral dryness using Kaplan-Meier curves with a log-rank test. Prediction accuracy was evaluated by the receiver operating characteristic (ROC) curve and the area under the curve (AUC). RESULTS: Median survival (95% confidence interval) in patients with oral dryness at the lingual mucosa was shorter than that in patients without oral dryness (17 [11-24] days vs. 28 [22-37] days, log-rank test, p <0.001), but not at the buccal mucosa. Time-dependent ROC revealed that the AUCs for 7-, 14-, 21-, and 28-day survival predictions were 0.72, 0.68, 0.61, and 0.59 with a cutoff value of 19.2%, respectively. The prevalence of performance status (PS) 4 and oxygen administration in the 7-day death group were higher than those in the non-7-day death group. A stratified analysis indicated that moisture degree <19.2% showed fair predictive performance with an AUC of 0.74 and 0.74, in the case of PS ≤3 or without oxygen administration. CONCLUSION: Oral dryness was associated with increased risk of mortality in palliative care patients. Moisture degree <19.2% at the lingual mucosa predicted less than 7-day survival.

Diagnostic accuracy of patient-reported dry mouth as a predictor for oral dryness in terminally ill cancer patients.

PURPOSE: The aim of the study was to determine the diagnostic accuracy of patient-reported dry mouth using an oral moisture-checking device in terminally ill cancer patients. METHODS: The study was conducted following the STARD guidelines, and the participants were recruited prospectively from the Palliative Care Unit, Kyoto Medical Center, Japan, between 1 January 2017 and 30 November 2018. Patients reporting dry mouth were asked to rate oral dryness on a 5-point rating scale. The outcome was oral dryness at the lingual mucosa, measured using an oral moisture-checking device. Receiver operating characteristic (ROC) curves were plotted, and the sensitivity, specificity, positive and negative predictive values (PPV and NPV), positive and negative likelihood ratios (LR), and overall diagnostic accuracy were calculated. RESULTS: Of 103 participants, the prevalence of oral dryness was 65.0%. ROC analysis indicated that patient-reported dry mouth was a poor predictor of oral dryness, with an area under the curve of 0.616 (95% confidence interval: 0.508-0.723), a sensitivity of 46.3%, a specificity of 75.8%, a PPV of 55.9%, an NPV of 68.1, a positive LR of 1.9, a negative LR of 0.7, and an overall diagnostic accuracy of 64.1%, with a cut-off value of 3 points. CONCLUSION: In conclusion, patient-reported dry mouth is not a useful parameter for the assessment of oral dryness in terminally ill cancer patients.

LDL-cholesterol and PCSK9 in patients with familial hypercholesterolemia: influence of PCSK9 variants under lipid-lowering therapy.

BACKGROUND: Familial hypercholesterolemia (FH), an autosomal dominant genetic disease with the elevated levels of low-density lipoprotein (LDL) cholesterol (LDL-C), increases the risk of coronary artery disease (CAD). The proprotein convertase subtilisin/kexin type 9 (PCSK9) gene is associated with FH. There is a positive relationship between circulating LDL-C and PCSK9 levels, a potential CAD condition, without lipid-lowering therapy (LLT); however, we do not know whether their correlation exists in FH patients under LLT. METHODS: This study compared the correlation of PCSK9 variants among patients with FH under LLT (n = 70; mean age, 53 years; male, 63%). LDLR, PCSK9 and APOB variants were analyzed using next-generation sequencing. RESULTS: The LDL-C and PCSK9 levels in patients with gain-of-function (GOF) variants of PCSK9 (n = 7) were mostly similar to those in patients with LDLR variants (n = 17) or variant-negative patients (n = 46). A significant positive correlation was observed between LDL-C and PCSK9 levels in patients with GOF variants of PCSK9 (r = 0.79, p = 0.04), but not in patients with LDLR variants or variant-negative patients. CONCLUSION: The LDL-C-PCSK9 correlation is suggested to be retained in FH patients with GOF variants of PCSK9 even under LLT, and these variants can be used as molecular markers for additional treatment with statins in FH patients.

Association between socioeconomic status and small-for-gestational-age in Japan: A single center retrospective cohort study.

AIM: Small-for-gestational-age (SGA) status has negative health consequences in neonates and later life. Low socioeconomic status (SES) is a reported risk factor for adverse birth outcomes, such as SGA and preterm birth (PTB). The present study investigated whether maternal SES is associated with adverse outcomes in Japanese pregnant women. METHODS: Retrospective data were collected for 1970 Japanese women with singleton pregnancies who delivered between January 2007 and December 2011 at a single center: low SES group (n = 197); and controls (n = 1773). Low SES was defined according to the criteria of the Japanese pregnant-childbirth hospitalization support policy system. RESULTS: The low SES group included a significantly higher proportion of young women, women with single marital status, greater parity, pre-pregnancy smoking and a lack of regular employment (P < 0.001, respectively). The crude odds ratio (OR) for the association between low maternal SES and SGA was 1.80 (95% confidence interval [CI] 1.15-2.82, P = 0.010). After adjustment for baseline maternal age, parity, body mass index, smoking and gestational weight gain, the adjusted OR for the association between low maternal SES and SGA was 1.92 (95% CI 1.17-3.17, P = 0.010). No significant association was found between maternal SES and PTB. CONCLUSION: The present results suggest that low maternal SES is associated with SGA births in the Japanese population. Mitigation of low maternal SES could be urgent public health to prevent disadvantage birth outcome.

JTE-607, a multiple cytokine production inhibitor, targets CPSF3 and inhibits pre-mRNA processing.

JTE-607 is a small molecule that was developed as an inflammatory cytokine inhibitor and also as an anti-leukemia reagent for monocytic leukemia. However, the mode of action of JTE-607 remains unknown. In this study, we identified JTE-607 to be a prodrug compound that is converted to an active form by ester hydrolysis. Furthermore, we determined that the active form of JTE-607 bound cleavage and polyadenylation specificity factor subunit 3 (CPSF3), using compound-immobilized affinity chromatography. CPSF3 is a 73-kDa subunit of the cleavage and polyadenylation specificity factor complex, which functions as an RNA endonuclease. The protein is involved in the 3'-end processing of messenger RNA precursors (pre-mRNAs) at the cleavage site located downstream of the poly(A) addition signal. We found that treatment with JTE-607 caused accumulation of pre-mRNAs. Furthermore, knockdown experiments showed that CPSF3 deficiency also caused accumulation of pre-mRNAs and suppressed the expression of inflammatory cytokines, like JTE-607. These findings indicated that CPSF3 is a direct target of JTE-607 and a new potential target for the treatment of disease-related abnormal cytokine production.

The study of metabolic improvement by nutritional intervention controlling endogenous GIP (Mini Egg study): a randomized, cross-over study.

BACKGROUND: Given the major role of glucose-dependent insulinotropic polypeptide (GIP) in the regulation of adiposity, this study examined the effects induced by a diet based on the Japanese tradition (SMART WASHOKU) on the visceral fat area (VFA) and GIP secretions. METHODS: Overweight/obese men (n = 21; mean age, 41.0 ± 9.0 years; mean BMI, 25.2 ± 2.0 kg/m2) without diabetes were placed on either a SMART WASHOKU or control meal for 2 weeks, in a randomized, cross-over setup with a four-week washout period. RESULTS: For the meal tolerance test, blood samples were collected at 0, 30, 60, 120, 180, and 240 min post-meal, followed by measuring blood glucose, insulin, GIP, and glucagon-like peptide-1 (GLP-1) levels. Relative to a control meal, SMART WASHOKU meal yielded significantly lower plasma postprandial GIP concentrations (AUC: 700.0 ± 208.0 vs. 1117.0 ± 351.4 pmol/L・4 h, P < 0.05); however, between meals, there was no significant difference in the levels of GLP-1, peptide YY, and ghrelin. Compared to the control meal, SMART WASHOKU intervention significantly reduced VFA and the levels of LDL-cholesterol, triglyceride, and HbA1c after the chronic meal intervention. CONCLUSIONS: In conclusion, a SMART WASHOKU meal may decrease VFA and improve metabolic parameters in overweight/obese men, possibly via suppressing GIP secretion.

Pretreatment Blood Pressure is a Simple Predictor of Hemorrhagic Infarction after Intravenous Recombinant Tissue Plasminogen Activator (rt-PA) Therapy.

BACKGROUND: Hemorrhagic infarction (HI) is among the most severe complications that can occur following the administration of intravenous recombinant tissue plasminogen activator (rt-PA). In the present study, we aimed to determine the optimal cut-off points of blood pressure (BP) for HI after rt-PA treatment, and to compare our findings with those for other prediction models. METHODS: We analyzed data from 109 consecutive patients with stroke treated at our hospital between 2009 and 2016. HI was confirmed via computed tomography or magnetic resonance imaging. Patients were classified into a symptomatic HI group, an asymptomatic HI group, and a non-HI group. BP was measured on admission and before rt-PA treatment. Glucose Race Age Sex Pressure Stroke Severity (GRASPS) and Totaled Health Risks in Vascular Events (THRIVE) scores were also calculated. Receiver operating characteristic (ROC) analysis was used to determine factors associated with symptomatic and asymptomatic HI. RESULTS: Among the 109 total patients, 25 patients developed symptomatic HI, while 22 patients developed asymptomatic HI. ROC analysis for predicting symptomatic and asymptomatic HI revealed that the area under the curve for pretreatment systolic BP (SBP) was .88 (95% confidence interval[CI]: .83-.94), while those for GRASPS and THRIVE scores were .75 (95% CI: .66-.85) and .69 (95% CI: .59-.79), respectively. We identified an optimal cut-off point of 160 mm Hg (sensitivity: 82.3%; specificity: 76.6%; diagnostic accuracy: 80.0%; positive predictive value: 76.6%; negative predictive value: 82.5%). CONCLUSIONS: Pre-treatment SBP may be a simple predictor of symptomatic and asymptomatic HI in patients with stroke undergoing rt-PA treatment.

Applicability of Supraclavicular Oxygenated and Total Hemoglobin Evaluated by Near-Infrared Time-Resolved Spectroscopy as Indicators of Brown Adipose Tissue Density in Humans.

Brown adipose tissue (BAT) may potentially be used in strategies for preventing lifestyle-related diseases. We examine evidence that near-infrared time-resolved spectroscopy (NIRTRS) is capable of estimating human BAT density (BAT-d). The parameters examined in this study are total hemoglobin [total-Hb]sup, oxygenated Hb [oxy-Hb]sup, deoxygenated Hb [deoxy-Hb]sup, Hb O2 saturation (StO2sup), and the reduced scattering coefficient in the supraclavicular region (µs'sup), where BAT deposits can be located; corresponding parameters in the control deltoid region are obtained as controls. Among the NIRTRS parameters, [total-Hb]sup and [oxy-Hb]sup show region-specific increases in winter, compared to summer. Further, [total-Hb]sup and [oxy-Hb]sup are correlated with cold-induced thermogenesis in the supraclavicular region. We conclude that NIRTRS-determined [total-Hb]sup and [oxy-Hb]sup are useful parameters for evaluating BAT-d in a simple, rapid, non-invasive manner.

Maslinic acid derived from olive fruit in combination with resistance training improves muscle mass and mobility functions in the elderly.

Maslinic acid, derived from olive fruit, reduces pro-inflammation cytokines, which are involved in muscle fiber atrophy. Therefore, the maslinic acid ingestion may enhance the muscular response to resistance training through anti-inflammatory action. We therefore conducted a parallel, double-blind, randomized, placebo-controlled trial that examined whether a combination of maslinic acid supplementation and resistance training improve mobility functions in community-dwelling elderly persons. Over a 12-week period, 36 participants underwent moderate resistance training and are assigned to the maslinic acid supplementation (n = 17, 60 mg/day) or the placebo (n = 19) group. At baseline and at 12-weeks, we assessed body composition, grip strength, walking speed, leg strength, mobility functions, and knee pain scores. Following the 12-weeks, skeletal muscle mass, segmental muscle mass (right arm, left arm, and trunk) and knee pain score of the right leg were significantly improved in the maslinic acid group, while there was no change or parameters had worsened in the placebo group. Grip strength of the better side significantly increased only in the maslinic acid group. These results suggest that maslinic acid supplementation combined with moderate resistance training may increase upper muscle mass and grip strength, and reduce knee pain, could be effective for preventing mobility-related disability in elderly persons. Clinical trial registration number: UMIN000017207.

The HIV-1 Tat Protein Is Monomethylated at Lysine 71 by the Lysine Methyltransferase KMT7.

The HIV-1 transactivator protein Tat is a critical regulator of HIV transcription primarily enabling efficient elongation of viral transcripts. Its interactions with RNA and various host factors are regulated by ordered, transient post-translational modifications. Here, we report a novel Tat modification, monomethylation at lysine 71 (K71). We found that Lys-71 monomethylation (K71me) is catalyzed by KMT7, a methyltransferase that also targets lysine 51 (K51) in Tat. Using mass spectrometry, in vitro enzymology, and modification-specific antibodies, we found that KMT7 monomethylates both Lys-71 and Lys-51 in Tat. K71me is important for full Tat transactivation, as KMT7 knockdown impaired the transcriptional activity of wild type (WT) Tat but not a Tat K71R mutant. These findings underscore the role of KMT7 as an important monomethyltransferase regulating HIV transcription through Tat.

ACTN3 GENE R577X POLYMORPHISM ASSOCIATED WITH HIGH-DENSITY LIPOPROTEIN CHOLESTEROL AND ADIPONECTIN IN RUGBY PLAYERS.

OBJECTIVE: To determine the relationship between the R577X polymorphism of the α-actinin-3 (ACTN3), which may play a role in the individual differences observed in the effects of exercise on health benefits and antiatherogenic markers (i.e., high-density lipoprotein cholesterol [HDL-C] and adiponectin) in athletes. METHODS: Seventy-six male rugby players (mean age 19.8 years) were enrolled in this study. Genomic DNA was extracted from peripheral blood samples, and restriction fragment length polymorphism-polymerase chain reactions were conducted to assess ACTN3 genotypes. Body mass index (BMI), waist circumference, serum lipids including HDL-C, and adiponectin levels were measured. Current smoking and alcohol intake habits were evaluated with a questionnaire. All of the parameters were compared between 2 groups displaying frequently observed genotypes: one group consisting of patients having either the R/R or R/X genotype and a second group with the X/X genotype. RESULTS: The frequency of the X allele was 0.55 and the distribution of the genotypes was 35.5% (n = 27) for X/X, 39.5% (n = 30) for R/X, and 25.0% (n = 19) for R/R. Serum HDL-C and adiponectin levels were significantly higher in X/X genotype compared to the R/R or R/X genotype (HDL-C 1.6 ± 0.3 [SD] vs. 1.4 ± 0.2 mmol/L; P<.01, adiponectin 8.8 ± 2.6 vs. 6.9 ± 2.3 µg/mL; P<.01), even after adjustments for confounders (P<.01). CONCLUSION: There may be a relationship between the ACTN3 genotype and HDL-C and adiponectin levels in rugby players. This may be useful information when determining the individual responses of antiatherogenic markers to exercise. ABBREVIATIONS: ACTN3 = α-actinin-3 BMI = body mass index CVD = cardiovascular disease HDL-C = high-density lipoprotein cholesterol LDL-C = low-density lipoprotein cholesterol R = arginine (R) at amino acid position 577 of the ACTN3 protein TC = total cholesterol TG = triglyceride X = truncation at amino acid position 577 of the ACTN3 protein.

Fasting Lipoprotein Lipase Protein Levels Can Predict a Postmeal Increment of Triglyceride Levels in Fasting Normohypertriglyceridemic Subjects.

BACKGROUND: Although a postprandial increment in triglyceride (TG) levels is considered to be a risk factor for atherogenesis, tests (e.g., fat load) to assess postprandial changes in TG levels cannot be easily applied to clinical practice. Therefore, fasting markers that predict postprandial TG states are needed to be developed. One current candidate is lipoprotein lipase (LPL) protein, a molecule that hydrides TGs. This study investigated whether fasting LPL levels could predict postprandial TG levels. METHODS: A total of 17 subjects (11 men, 6 women, mean age 52 ± 11 years) with normotriglyceridemia during fasting underwent the meal test. Several fasting parameters, including LPL, were measured for the area under the curve of postprandial TGs (AUC-TG). RESULTS: The subjects' mean fasting TG level was 1.30 mmol/l, and their mean LPL level was 41.6 ng/ml. The subjects' TG levels increased after loading (they peaked after two postprandial hours). Stepwise multiple regression analysis demonstrated that fasting TG levels were a predictor of the AUC-TG. In addition, fasting LPL mass levels were found to be a predictor of the AUC-TG (ß = 0.65, P < 0.01), and this relationship was independent of fasting TG levels. CONCLUSION: Fasting LPL levels may be useful to predict postprandial TG increment in this population.

Efficacy of a 3-month lifestyle intervention program using a Japanese-style healthy plate on body weight in overweight and obese diabetic Japanese subjects: a randomized controlled trial.

BACKGROUND AND OBJECTIVES: The portion size of food is a determinant of energy intake, linking with obese traits. A healthy plate for portion control has recently been made in a Japanese style. The aim of the current study was to assess the efficacy of a lifestyle intervention program using the Japanese-style healthy plate on weight reduction in overweight and obese diabetic Japanese subjects. METHODS: We randomized overweight and obese diabetic subjects (n = 19, 10 women) into an intervention group including educational classes on lifestyle modification incorporating the healthy plate (n = 10) or a waiting-list control group (n = 9). The intervention period was three months, and the educational classes using the healthy plate were conducted monthly in a group session for the intervention group. The body weight, blood glycemic and metabolic measures, and psychosocial variables were measured at the baseline and after the 3-month intervention in both groups. The impression of the intervention was interviewed using a structured questionnaire. RESULTS: There was one drop-out in the control group. No adverse events were reported in the groups. Subjects in the intervention group had a greater weight change from baseline to the end of the 3-month intervention period (-3.7 +/- 2.5 [SD] kg in the intervention group vs. -0.1 +/- 1.4 kg in the control group, P = 0.002). Most subjects recorded that the use of a healthy plate could be recommended to other people. CONCLUSIONS: The lifestyle intervention program using the Japanese-style healthy plate, which was developed for portion control, may effectively reduce body weight in overweight and obese diabetic subjects in Japan. Further studies are needed to establish the efficacy of this methodology on weight management.

High-density lipoprotein size distribution can differ between subjects with alcoholic and non-alcoholic fatty liver disease.

BACKGROUND: While alcohol consumption is associated with levels of high-density lipoprotein (HDL)-cholesterol (HDL-C), a cardiovascular risk marker, HDL size distribution has yet to be characterized in subjects with alcoholic fatty liver disease (AFLD) and non-alcoholic fatty liver disease (NAFLD). METHODS: The present study compared HDL subfractional characteristics between subjects with AFLD (36 men, age 61 +/- 14) and NAFLD (35 men, age 65 +/- 13), recruited during general health check-ups. Serum HDL subfractions were measured with the electrophoretic separation of lipoproteins employing the Lipoprint system. RESULTS: The subjects with AFLD had a significantly greater proportion of small-sized HDL part (6.6 +/- 5.7%) than those with NAFLD (3.8 +/- 4.9%, p = 0.029). CONCLUSIONS: More percentages of small-sized HDL part were observed in the subjects with AFLD than in those with NAFLD in Japanese general population. Whether the difference of HDL size is associated with cardiovascular manifestations should be studied further.

Innovations and applications of ketone body monitoring in diabetes care.

Ketone bodies, comprising ß-hydroxybutyric acid (BHB), acetoacetate (AcAc), and acetone, play a vital role as essential energy substrates. In individuals with diabetes, ketone bodies can be elevated under various conditions, including diabetic ketoacidosis, use of sodium-glucose transporter type 2 (SGLT2) inhibitors, and extreme carbohydrate restriction. There are three methods for measuring ketone bodies. Urine ketone analysis (AcAc) is a standard clinical test, whereas blood ketone testing (BHB+AcAc) is valuable in identifying or resolving diabetic ketoacidosis. Recently, technology for measuring breath acetone has been introduced, which provides an easy means of monitoring ketogenic diets in obese individuals. The basic breath alcohol detector also reacts with breath acetone. Therefore, it is important for professional drivers taking SGLT2 inhibitors to be cautious as workplace breath alcohol detectors may show false-positive results. Conversely, if a positive result is obtained, a detailed examination of ketosis is necessary. This review provides an overview of ketone body measurements in individuals with diabetes.