Acute metabolic responses to a high-carbohydrate meal in outpatients with type 2 diabetes treated with a low-carbohydrate diet: a crossover meal tolerance study

<p>Abstract</p> <p>Background</p> <p>A low-carbohydrate diet (LCD) achieves good glycemic control in type 2 diabetes (T2DM) compared with a high-carbohydrate diet. With respect to energy metabolism, acute metabolic responses to high-carbohydrate meals (HCMs) have not been determined in LCD patients with T2DM.</p> <p>Subjects and methods</p> <p>We enrolled 31 subjects with T2DM (mean age: 62 yrs, mean hemoglobin A1c level: 6.9%), of whom 13 were on a strict LCD (26% carbohydrate diet), and 18 a moderate one (44% carbohydrate diet). Two isocaloric meals were administered to all subjects in a randomized crossover design. The carbohydrate:protein:fat ratios of HCMs and low-carbohydrate meals (LCMs) were 59:20:21 and 7:20:73, respectively. Serum β-hydroxybutyrate, acetoacetate, free fatty acids (FFAs), triglyceride and insulin, and plasma glucose concentrations were measured for 120 minutes after the intake of each meal.</p> <p>Results</p> <p>HCMs rapidly decreased postprandial β-hydroxybutyrate, acetoacetate and FFA concentrations within 2 hours in all patients in combination with rapid increases in serum insulin and plasma glucose, while LCMs increased or did not change β-hydroxybutyrate, acetoacetate and FFAs (<it>P </it>< 0.001 for all). HCMs did not change postprandial triglyceride concentrations over 2 hours, while LCMs gradually increased them (<it>P </it>< 0.001).</p> <p>HCMs sharply and rapidly decreased postprandial β-hydroxybutyrate and acetoacetate concentrations in strict LCD subjects over 2 hours, but only slightly decreased them in moderate LCD subjects (<it>P </it>< 0.001, difference between strict and moderate LCD subjects). The parameter Δketone bodies (level at 120 minutes - level at baseline) was significantly correlated with the insulinogenic index (Spearman's r = 0.503 for β-hydroxybutyrate and 0.509 for acetoacetate), but not with total insulin secretory capacity. Moreover, HCMs slightly decreased postprandial triglyceride levels in strict LCD subjects but somewhat increased them in the moderate LCD subjects (<it>P </it>= 0.002). The parameter Δtriglyceride was significantly correlated with background dietary %carbohydrate (Spearman's r = 0.484).</p> <p>Conclusion</p> <p>HCMs rapidly decreased postprandial ketone body concentrations in T2DM patients treated with a LCD. The decreases were more remarkable in strict than in moderate LCD subjects. HCMs slightly decreased postprandial triglyceride levels in strict LCD subjects. The parameter Δketone bodies was significantly correlated with the insulinogenic index, as was Δtriglyceride with background dietary %carbohydrate.</p

One-Year Period Prevalence of Oral Aphthous Ulcers and Oral Health-Related Quality of Life in Patients with Behçet&apos;s Disease

The aim of this study was to investigate the 1-year period prevalence of oral aphthous ulcers (OAUs) and their association with oral health-related quality of life (OHQOL) in patients with Behçet&apos;s disease (BD) and in the general population. In this cross-sectional study, 675 patients with Behçet&apos;s disease (BD group) and 1,097 males and females in the Japanese general population (control group) completed both questionnaires on their OAU status during the prior year and the General Oral Health Assessment Index (GOHAI). In the BD group, 84% of patients reported experiencing an OAU during the previous year, and the mean number of OAUs/year was 13. In the control group, 31% of individuals experienced an OAU during the previous year, and the mean number of OAUs/year was one. Multivariate analysis indicated that both BD patients (OR, 6.2; 95% CI, 4.8-8.0) and controls (OR, 2.6; 95% CI, 2.0-3.5) who had OAUs at least twice per year were more likely to have GOHAI scores below the norm than were controls who had fewer than two OAUs per year. The association between HLA-B * 51 and OAUs remains unknown. The presence of OAUs has a negative effect on the OHQOL of patients with BD

Alcohol Intake and Serum Lipids–Genetic Modification

Background: Although beneficial associations have been reported between moderate alcohol intake and the serum lipid profile, it is unclear whether polymorphisms in alcohol-metabolizing enzymes can modify these associations. Here, we assessed the effects of ADH1B His48Arg (rs1229984), ALDH2 Glu504Lys (rs671), and their combination on these associations. Furthermore, we examined if the findings for ALDH2 could be replicated. Methods: We categorized 889 male participants in the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study into two groups based on presence or absence of minor allele(s) or four groups based on genotype combinations. We performed regression analyses of serum lipid concentrations on alcohol intake, with multivariable adjustment. The replication study was conducted among 2,562 men in the Shizuoka part of the J-MICC Study. Results: The ALDH2 Glu/Lys or Lys/Lys groups showed significant decreases in serum low-density lipoprotein (LDL) cholesterol with increasing alcohol consumption; the coefficient per intake increase of 10 g/day was −2.49 mg/dL (95% confidence interval [CI], −3.85 to −1.13), and a significant interaction with the polymorphism was confirmed (P for interaction = 0.006). This inverse correlation was more evident among the ADH1B His/His + ALDH2 Glu/Lys or Lys/Lys groups (−3.24 mg/dL, 95% CI, −5.03 to −1.45). Serum triglycerides were positively associated with alcohol consumption in the ADH1B His/His group (P for interaction = 0.020). The stronger association between serum LDL cholesterol and alcohol consumption in the ALDH2 Glu/Lys or Lys/Lys groups was replicated. Conclusions: The ALDH2 Glu504Lys polymorphism can modify the association between alcohol intake and serum LDL cholesterol in Japanese men

A Proposal for Practical Diagnosis of Renal Hypouricemia : Evidenced from Genetic Studies of Nonfunctional Variants of URAT1/SLC22A12 among 30,685 Japanese Individuals

Background: Renal hypouricemia (RHUC) is characterized by a low serum uric acid (SUA) level and high fractional excretion of uric acid (FEUA). Further studies on FEUA in hypouricemic individuals are needed for a more accurate diagnosis of RHUC. Methods: In 30,685 Japanese health-examination participants, we genotyped the two most common nonfunctional variants of URAT1 (NFV-URAT1), W258X (rs121907892) and R90H (rs121907896), in 1040 hypouricemic individuals (SUA ≤ 3.0 mg/dL) and 2240 individuals with FEUA data. The effects of NFV-URAT1 on FEUA and SUA were also investigated using linear and multiple regression analyses. Results: Frequency of hypouricemic individuals (SUA ≤ 3.0 mg/dL) was 0.97% (male) and 6.94% (female) among 30,685 participants. High frequencies of those having at least one allele of NFV-URAT1 were observed in 1040 hypouricemic individuals. Furthermore, NFV-URAT1 significantly increased FEUA and decreased SUA, enabling FEUA and SUA levels to be estimated. Conversely, FEUA and SUA data of hypouricemic individuals are revealed to be useful to predict the number of NFV-URAT1. Conclusions: Our findings reveal that specific patterns of FEUA and SUA data assist with predicting the number of nonfunctional variants of causative genes for RHUC, and can also be useful for practical diagnosis of RHUC even before genetic tests

Genetic variants of SLC17A1 are associated with cholesterol homeostasis and hyperhomocysteinaemia in Japanese men

Hyperuricaemia is an undisputed and highly predictive biomarker for cardiovascular risk. SLC17A1, expressed in the liver and kidneys, harbours potent candidate single nucleotide polymorphisms that decrease uric acid levels. Therefore, we examined SLC17A1 polymorphisms (rs1165196, rs1179086 and rs3757131), which might suppress cardiovascular risk factors and that are involved in liver functioning, via a large-scale pooled analysis of the Japanese general population in a cross-sectional study. Using data from the Japan Multi-Institutional Collaborative Cohort Study, we identified 1842 participants of both sexes, 35–69-years-old, having the requisite data and analysed their SLC17A1 genotypes. In men, logistic regression analyses revealed that minor alleles in SLC17A1 polymorphisms (rs1165196 and rs3757131) were associated with a low-/high-density lipoprotein cholesterol ratio >2.0 (rs1165196: odds ratio [OR], 0.703; 95% confidence interval [CI], 0.536–0.922; rs3757131: OR, 0.658; 95% CI, 0.500–0.866) and with homocysteine levels of >10.0 nmol/mL (rs1165196: OR, 0.544; 95% CI, 0.374–0.792; rs3757131: OR, 0.509; 95% CI, 0.347–0.746). Therefore, these polymorphisms had dominant negative effects on cholesterol homeostasis and hyperhomocysteinaemia, in men, independent of alcohol consumption, physical activity, or daily energy and nutrition intake. Thus, genetic variants of SLC17A1 are potential biomarkers for altered cholesterol homeostasis and hyperhomocysteinaemia in Japanese men

Association of Dietary Acid Load with the Prevalence of Metabolic Syndrome among Participants in Baseline Survey of the Japan Multi-Institutional Collaborative Cohort Study

The association between dietary acid load and metabolic syndrome (MetS) has not been fully investigated. A cross-sectional study was performed on 14,042 men and 14,105 women (aged 35–69 years) who participated in a baseline survey of the Japan Multi-Institutional Collaborative Cohort study. Dietary acid load was assessed using the net-endogenous-acid-production (NEAP) score that is closely correlated with the rate of renal net acid excretion. MetS was diagnosed according to the Joint Interim Statement Criteria of 2009 using body-mass index instead of waist circumference. After adjusting for potential confounders, higher NEAP scores were associated with a significantly increased odds ratio (OR) of MetS, obesity, high blood pressure, and high fasting blood glucose. These associations remained significant after further adjustment for carbohydrate intake or two nutrient-pattern scores significantly associated with MetS. After adjustment for fiber, iron, potassium, and vitamin pattern scores, the OR of MetS for the highest quartile of NEAP scores, relative to the lowest quartile, was 1.25 (95% confidence interval 1.12–1.39). There was no significant interaction between sex, age, or body-mass index and NEAP. Higher dietary acid load was associated with a higher prevalence of MetS and several of its components, independently of carbohydrate intake or nutrient patterns

Sedentary Time and All-Cause Mortality

BACKGROUND: This study aimed to determine the association between sedentary time and mortality with regard to leisure‐time physical activity with or without cardiometabolic diseases such as hypertension, dyslipidemia, and diabetes mellitus. METHODS AND RESULTS: Using data from the J‐MICC (Japan Multi‐Institutional Collaborative Cohort) Study, 64 456 participants (29 022 men, 35 434 women) were analyzed. Hazard ratios (HRs) and 95% CIs were used to characterize the relative risk of all‐cause mortality to evaluate its association with sedentary time (categorical variables: <5, 5 to <7, 7 to <9, ≥9 h/d and 2‐hour increments in exposure) according to the self‐reported hypertension, dyslipidemia, and diabetes mellitus using a Cox proportional hazards model. A total of 2257 participants died during 7.7 years of follow‐up. The corresponding HRs for each 2‐hour increment in sedentary time among participants with all factors, no factors, hypertension, dyslipidemia, and diabetes mellitus were 1.153 (95% CI, 1.114–1.194), 1.125 (95% CI, 1.074–1.179), 1.202 (95% CI, 1.129–1.279), 1.176 (95% CI, 1.087–1.273), and 1.272 (95% CI, 1.159–1.396), respectively. Furthermore, when analyzed according to the combined different factors (hypertension, dyslipidemia, and diabetes mellitus), HRs increased with each additional factor, and participants reporting all 3 conditions had the highest HR of 1.417 (95% CI, 1.162–1.728) independently of leisure‐time metabolic equivalents. CONCLUSIONS: The association between sedentary time and increased mortality is stronger among patients with hypertension, dyslipidemia, and diabetes mellitus regardless of leisure‐time physical activity in a large Japanese population