Relationship between hemoglobin A1c and cardiovascular disease in mild-to-moderate hypercholesterolemic Japanese individuals: subanalysis of a large-scale randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Although the ADA/EASD/IDF International Expert Committee recommends using hemoglobin A1c (HbA1c) to define diabetes, the relation between HbA1c and cardiovascular disease (CVD) has not been thoroughly investigated. We analyzed this relation using clinical data on Japanese individuals with hypercholesterolemia.</p> <p>Methods</p> <p>In the large-scale MEGA Study 7832 patients aged 40 to 70 years old with mild-to-moderate hypercholesterolemia without CVD were randomized to diet alone or diet plus pravastatin and followed for >5 years. In the present subanalysis of that study a total of 4002 patients with baseline and follow-up HbA1c data were stratified according to having an average HbA1c during the first year of follow-up <6.0%, 6.0%-<6.5%, or ≥6.5% and their subsequent 5-year incidence rates of CVD compared according to sex, low-density lipoprotein cholesterol (LDL-C), and treatment arm.</p> <p>Results</p> <p>Overall, risk of CVD was significantly 2.4 times higher in individuals with HbA1c ≥6.5% versus <6.0%. A similar relation was noted in men and women (hazard ratio [HR], 2.1; p <0.01 and HR, 3.0; p <0.01, respectively) and was regardless of treatment arm (diet alone group: HR, 2.2; p <0.001; diet plus pravastatin group: HR, 1.8; p = 0.02). Spline curves showed a continuous risk increase according to HbA1c level in all subpopulations studied.</p> <p>Conclusions</p> <p>In hypercholesterolemic individuals the risk of CVD increases linearly with HbA1c level. This significant contribution by elevated HbA1c to increased CVD is independent of pravastatin therapy, and thus requires appropriate HbA1c management in addition to lipids reduction.</p

身体消費エネルギー量と総白血球数，白血球分画の関係

内科学（第三）講座 講座主任　内潟安子教授退任記念特別

Preventive Effects of Salacia reticulata on Obesity and Metabolic Disorders in TSOD Mice

The extracts of Salacia reticulata (Salacia extract), a plant that has been used for the treatment of early diabetes, rheumatism and gonorrhea in Ayurveda, have been shown to have an anti-obesity effect and suppress hyperglycemia. In this study, the effects of Salacia extract on various symptoms of metabolic disorder were investigated and compared using these TSOD mice and non-obese TSNO mice. Body weight, food intake, plasma biochemistry, visceral and subcutaneous fat (X-ray and CT), glucose tolerance, blood pressure and pain tolerance were measured, and histopathological examination of the liver was carried out. A significant dose-dependent decline in the gain in body weight, accumulation of visceral and subcutaneous fat and an improvement of abnormal glucose tolerance, hypertension and peripheral neuropathy were noticed in TSOD mice. In addition, hepatocellular swelling, fatty degeneration of hepatocytes, inflammatory cell infiltration and single-cell necrosis were observed on histopathological examination of the liver in TSOD mice. Salacia extract markedly improved these symptoms upon treatment. Based on the above results, it is concluded that Salacia extract has remarkable potential to prevent obesity and associated metabolic disorders including the development of metabolic syndrome

Impact of population aging on trends in diabetes prevalence : A meta-regression analysis of 160,000 Japanese adults

Aims/IntroductionTo provide age- and sex-specific trends, age-standardized trends, and projections of diabetes prevalence through the year 2030 in the Japanese adult population. Materials and MethodsIn the present meta-regression analysis, we included 161,087 adults from six studies and nine national health surveys carried out between 1988 and 2011 in Japan. We assessed the prevalence of diabetes using a recorded history of diabetes or, for the population of individuals without known diabetes, either a glycated hemoglobin level of 6.5% (48mmol/mol) or the 1999 World Health Organization criteria (i.e., a fasting plasma glucose level of 126mg/dL and/or 2-h glucose level of 200mg/dL in the 75-g oral glucose tolerance test). ResultsFor both sexes, prevalence appeared to remain unchanged over the years in all age categories except for men aged 70years or older, in whom a significant increase in prevalence with time was observed. Age-standardized diabetes prevalence estimates based on the Japanese population of the corresponding year showed marked increasing trends: diabetes prevalence was 6.1% among women (95% confidence interval [CI] 5.5-6.7), 9.9% (95% CI 9.2-10.6) among men, and 7.9% (95% CI 7.5-8.4) among the total population in 2010, and was expected to rise by 2030 to 6.7% (95% CI 5.2-9.2), 13.1% (95% CI 10.9-16.7) and 9.8% (95% CI 8.5-12.0), respectively. In contrast, the age-standardized diabetes prevalence using a fixed population appeared to remain unchanged. ConclusionsThis large-scale meta-regression analysis shows that a substantial increase in diabetes prevalence is expected in Japan during the next few decades, mainly as a result of the aging of the adult population.Peer reviewe

Cardiovascular disease, chronic kidney disease, and diabetes mortality burden of cardiometabolic risk factors from 1980 to 2010: A comparative risk assessment

Background: High blood pressure, blood glucose, serum cholesterol, and BMI are risk factors for cardiovascular diseases and some of these factors also increase the risk of chronic kidney disease and diabetes. We estimated mortality from cardiovascular diseases, chronic kidney disease, and diabetes that was attributable to these four cardiometabolic risk factors for all countries and regions from 1980 to 2010. Methods: We used data for exposure to risk factors by country, age group, and sex from pooled analyses of population-based health surveys. We obtained relative risks for the effects of risk factors on cause-specific mortality from meta-analyses of large prospective studies. We calculated the population attributable fractions for each risk factor alone, and for the combination of all risk factors, accounting for multicausality and for mediation of the effects of BMI by the other three risks. We calculated attributable deaths by multiplying the cause-specific population attributable fractions by the number of disease-specific deaths. We obtained cause-specific mortality from the Global Burden of Diseases, Injuries, and Risk Factors 2010 Study. We propagated the uncertainties of all the inputs to the final estimates. Findings: In 2010, high blood pressure was the leading risk factor for deaths due to cardiovascular diseases, chronic kidney disease, and diabetes in every region, causing more than 40% of worldwide deaths from these diseases; high BMI and glucose were each responsible for about 15% of deaths, and high cholesterol for more than 10%. After accounting for multicausality, 63% (10·8 million deaths, 95% CI 10·1-11·5) of deaths from these diseases in 2010 were attributable to the combined effect of these four metabolic risk factors, compared with 67% (7·1 million deaths, 6·6-7·6) in 1980. The mortality burden of high BMI and glucose nearly doubled from 1980 to 2010. At the country level, age-standardised death rates from these diseases attributable to the combined effects of these four risk factors surpassed 925 deaths per 100 000 for men in Belarus, Kazakhstan, and Mongolia, but were less than 130 deaths per 100 000 for women and less than 200 for men in some high-income countries including Australia, Canada, France, Japan, the Netherlands, Singapore, South Korea, and Spain. Interpretation: The salient features of the cardiometabolic disease and risk factor epidemic at the beginning of the 21st century are high blood pressure and an increasing effect of obesity and diabetes. The mortality burden of cardiometabolic risk factors has shifted from high-income to low-income and middle-income countries. Lowering cardiometabolic risks through dietary, behavioural, and pharmacological interventions should be a part of the global response to non-communicable diseases. Funding: UK Medical Research Council, US National Institutes of Health. © 2014 Elsevier Ltd

Poor Eating Behaviors Related to the Progression of Prediabetes in a Japanese Population: An Open Cohort Study

This study aimed to examine lifestyle factors associated with the change in glucose categories among individuals without diabetes. We analyzed cohort data of medical check-ups at baseline between April 2008 and December 2012. The primary and secondary outcomes were the change in glucose categories from normoglycemia (glycated hemoglobin (HbA1c) &lt; 5.7% and fasting plasma glucose (FPG) &lt; 5.6 mmol/L) to prediabetes (HbA1c 5.7&ndash;6.4% or FPG 5.6&ndash;6.9 mmol/L) and from prediabetes to normoglycemia. During a mean follow-up of 2.4 years, 7083 of 57,018 individuals with normoglycemia developed prediabetes, whereas 4629 of 9926 individuals with prediabetes returned to normoglycemia. Factors associated with progression to prediabetes were baseline BMI (hazard ratio [95% confidence interval]: 1.08 [1.07&ndash;1.09]), change in BMI during follow-up (1.05 [1.03&ndash;1.07]), late dinner/snacking (1.16 [1.10&ndash;1.22]), skipping breakfast (1.12 [1.06&ndash;1.18]), and heavy alcohol consumption (1.33 [1.24&ndash;1.42]). Factors associated with return to normoglycemia from prediabetes were baseline BMI (0.94 [0.93&ndash;0.95]) and change in BMI during follow-up (0.95 [0.93&ndash;0.97]). In conclusion, poor eating behaviors, such as skipping breakfast, late dinner/snacking, and heavy alcohol consumption, were associated with the progression from normoglycemia to prediabetes

総白血球数とその分画,空腹時インスリン,メタボリックシンドロームの関係

(医学部内科学(第三)教室岩本安彦教授退任記念特別号

総白血球数とその分画,空腹時インスリン,メタボリックシンドロームの関係

(医学部内科学(第三)教室岩本安彦教授退任記念特別号