Eiko Takahashi

Optimal reference interval for homeostasis model assessment of insulin resistance in a Japanese population

The aim of the present study was to establish a reference interval for homeostasis model assessment of insulin resistance (HOMA‐IR) in a Japanese population based on the C28‐A3 document from the Clinical and Laboratory Standards Institute (CLSI). We selected healthy subjects aged 20–79 years, with fasting plasma glucose < 100 mg/dL, body mass index < 25 kg/m2 and alanine aminotransferase < 31 U/L. HOMA‐IR values were log transformed, values beyond mean ± 3 standard deviations (SD) were truncated, and the mean ± 2 SD of log HOMA‐IR values were taken as the upper and lower reference limits of HOMA‐IR. We selected 2173 subjects as reference individuals, and 2153 subjects were used for analysis. The reference interval for HOMA‐IR was established as between 0.4 and 2.4. This represents the first reference interval study for HOMA‐IR that applies the stringent CLSI C28‐A3 document. HOMA‐IR ≥ 2.5 should be considered a reasonable indicator of insulin resistance in Japanese. (J Diabetes Invest, doi: 10.1111/j.2040‐1124.2011.00113.x, 2011)

Self-rated health as a comprehensive indicator of lifestyle-related health status

ObjectivesTo evaluate the usefulness of self-rated health (SRH) as a comprehensive indicator of lifestyle-related health status by examining the relationships between SRH and: (1) history of cancer and cardiovascular disease; (2) treatment of hypertension, diabetes, and dyslipidemia; (3) abnormalities in clinical parameters including blood pressure, fasting glucose, and lipids; and (4) lifestyle habits.Methods3744 health-check examinees at Tokai University Hachioji Hospital seen between April 2009 and March 2010 were enrolled. SRH was graded as “good,” “relatively good,” “relatively poor,” or “poor.” For statistical comparison, the differences among “healthy” (=good), “relatively healthy” (=relatively good), and “unhealthy” (=relatively poor plus poor) groups were examined. Mantel–Haenszel odds ratios were calculated to remove the confounding effect of age, using the healthy group as the reference. The Mantel-extension method was used as a trend test.Results1049 subjects rated their health as good, 2194 as relatively good, 428 as relatively poor, and 73 as poor. The prevalence of all diseases showed significant odds ratios and trends as SRH deteriorated. Obesity, blood pressure, glucose metabolism, and lipids deteriorated significantly as SRH became poorer, and a trend was observed in all parameters. Weight change, exercise, smoking, and rest showed significant odds ratios and trends as SRH deteriorated.ConclusionSRH appears useful as a comprehensive indicator of lifestyle-related health status.

HDL2-cholesterol/HDL3-cholesterol ratio was associated with insulin resistance, high-molecular-weight adiponectin, and components for metabolic syndrome in Japanese

AIMS Recent data have suggested a relationship between the high-density lipoprotein (HDL) subclass ratio and metabolic syndrome (MetS). However, limited information is available regarding the relationships between the HDL subclass ratio and insulin resistance, associated adipocytokine levels, and MetS components. The associations of the high-density lipoprotein 2 cholesterol (HDL2-C) to high-density lipoprotein 3 cholesterol (HDL3-C) ratio with the homeostasis model assessment of insulin resistance (HOMA-IR) index, high-molecular-weight adiponectin (HMW-Ad) levels, and MetS components were examined. METHODS The study included 1155 Japanese subjects who met our inclusion criteria and underwent an annual health examination that included an HDL subclass analysis. RESULTS The HDL2-C/HDL3-C ratio and the HMW-Ad level gradually decreased as the number of MetS components increased. In contrast, HOMA-IR gradually increased as the number of MetS components increased. The HDL2-C/HDL3-C ratio correlated inversely with HOMA-IR and positively with the HMW-Ad level. A strong positive correlation was observed between the HDL2-C/HDL3-C ratio and the HDL-C level. The HDL2-C/HDL3-C ratio exhibited moderate negative correlations with the body mass index, waist circumference, and triglyceride level. Weak negative correlations were observed for the HDL2-C/HDL3-C ratio with the systolic and diastolic blood pressure and fasting plasma glucose levels. CONCLUSIONS Our data indicated that the HDL2-C/HDL3-C ratio was associated with insulin resistance, the HMW-Ad level, and MetS components, and it was useful for evaluating MetS in Japanese individuals.

Optimal cut-off point for homeostasis model assessment of insulin resistance to discriminate metabolic syndrome in non-diabetic Japanese subjects.

We have recently established a ‘health‐associated’ reference interval of homeostasis model assessment of insulin resistance (HOMA‐IR) between 0.4 and 2.4. In the present study, the aim was to establish a ‘decision‐based’ limit of HOMA‐IR for the discrimination of metabolic syndrome (MetS) in non‐diabetic Japanese subjects. The receiver–operating characteristic curve of HOMA‐IR for detecting MetS was developed using data from 6868 non‐diabetic subjects (3727 men, 3141 women). The optimal cut‐off point was determined based on the point that yielded the minimum value of the square root of [(1 – sensitivity)2 + (1 – specificity)2]. HOMA‐IR = 1.7 was determined as the optimal cut‐off value, with a sensitivity and specificity of 73.4% and 70.5% for men, and 81.5% and 77.0% for women, respectively. In conclusion, the optimal cut‐off value for HOMA‐IR to discriminate MetS in non‐diabetic Japanese subjects appears to be 1.7. (J Diabetes Invest, doi: 10.1111/j.2040‐1124.2012.00194.x, 2012)

Status of Dyslipidemia Treatment in Japanese Adults: An Analysis of the 2009 Japan Society of Ningen Dock Database

OBJECTIVE The Japan Atherosclerosis Society (JAS) has recommended serum lipid management goals (SLMGs) based on the coronary heart disease (CHD) risk classification included in its 2007 guidelines for the diagnosis and prevention of atherosclerotic cardiovascular disease in the Japanese population (JAS GL 2007). The Japan Society of Ningen Dock created a database of subjects receiving annual health examinations at 21 institutes nationwide. Using this database, we evaluated the efficacy of current treatment for patients with dyslipidemia by identifying risk factors for CHD development, based on the JAS recommendations. METHODS This multicenter, retrospective study was conducted using data obtained from 21 institutions across Japan. 17,991 adults taking dyslipidemia medications were enrolled. The JAS GL 2007 was used for evaluation. Since the guideline indicated separate goals (secondary prevention for subjects with a prior history of CHD and primary prevention for those with other CHD risk factors), we evaluated the percentages of goals met. The serum low-density lipoprotein cholesterol (LDL-C) levels were calculated using the Friedewald formula. The LDL-C level was measured using a direct homogeneous assay if the triglycerides (TG) level was 400 mg/dL or higher. RESULTS The achievement rates of the SLMGs were as follows: LDL-C, 72.3%; high-density lipoprotein cholesterol (HDL-C), 94.6%; and TG, 69.7%. CONCLUSION Our results regarding Japanese patients receiving dyslipidemia treatment for CHD prevention identified insufficient reductions in the levels of LDL-C and TG in those at high risk for CHD and suggest the need for more aggressive lipid-lowering therapy.

Non-HDL Cholesterol is a More Superior Predictor of Small-Dense LDL Cholesterol than LDL Cholesterol in Japanese Subjects with TG Levels ＜400 mg/dL

Aim: The Japan Atherosclerosis Society (JAS) guidelines for the diagnosis and treatment of hyperlipidemia in Japanese adults recommend using low-density lipoprotein cholesterol (LDL-C) calculated by Friedewald formula (F_LDL-C) for subjects with triglyceride (TG) levels <400 mg/dL and non-high-density lipoprotein cholesterol (non-HDL-C) levels for subjects with TG levels ≥400 mg/dL. Because small-dense LDL particles are more atherogenic than large LDL particles, we sought the better lipid parameter which was more reflective of the high small-dense LDL-C (sdLDL-C) levels in subjects with TG levels <400 mg/dL. Methods: This study included 769 Japanese subjects who met our inclusion criteria and underwent an annual health examination, including sdLDL-C analyses. Results: The correlation coefficient of non-HDL-C for sdLDL-C (r = 0.760) was significantly higher than that of F_LDL-C (r = 0.601). The area under the curve (95% confidence interval) was 0.771 (0.731, 0.811) for F_LDL-C and 0.871 (0.842, 0.901) for non HDL-C, which showed significantly higher predictive value for more than fourth quartile value of sdLDL-C (46 mg/dL). The optimal cut-off point of non-HDL-C was 158 mg/dL. Even in subjects stratified by waist circumstance, homeostasis model assessment of insulin resistance, TG, and F_LDL-C levels and non-HDL-C showed stronger relationships with sdLDL-C than F_LDL-C. Moreover, non-HDL-C showed a better relationship with sdLDL-C than total cholesterol (TC), TC/HDL-C, and non-HDL-C/HDL-C. Conclusion: Our data suggested that non-HDL-C is superior to F_LDL-C and one of the reliable surrogate lipid markers of sdLDL-C in Japanese subjects with TG levels <400 mg/dL.

Association between insulin resistance and metabolic syndrome risk factors in Japanese.

Aims/Introduction:  It is important to identify individuals at risk of metabolic syndrome (MetS), namely those with insulin resistance. Therefore, the aim of the present study was to find anthropometric and metabolic parameters that can better predict insulin resistance.

Lifestyle and glycemic control in Japanese adults receiving diabetes treatment: An analysis of the 2009 Japan Society of Ningen Dock database

We investigated the level of glycemic control in 7020 patients treated with diabetes medications. We found that the overall mean HbA1c was 7.3% (56 mmol/mol). Over half had HbA1c levels ≥7.0% (53 mmol/mol) and poorer glycemic control was associated with unhealthy lifestyle habits.

HDL2/HDL3 Ratio Changes, Metabolic Syndrome Markers, and Other Factors in a Japanese Population

AIM AND METHODS The high-density lipoprotein 2 cholesterol (HDL2-C) to HDL3-C ratio is associated with insulin resistance, high-molecular-weight adiponectin (HMW-Ad), and metabolic syndrome (MetS) components and is useful for evaluating MetS in Japanese individuals. We investigated potential associations between changes in HDL2-C/HDL3-C and changes in MetS components, insulin resistance, adipocytokine, lipids, and lifestyle habits in 892 Japanese subjects who underwent annual health examinations twice at a mean interval of 1.1 years. Study subjects were divided into three groups on the basis of HDL2-C/HDL3-C changes. RESULTS Average changes in waist circumference (WC) and HDL-C were significantly lower and higher, respectively, in the 0 to ＜0.5 and ≥0.5 HDL2-C/HDL3-C change groups compared with those in the reference group (＜0 HDL2-C/HDL3-C change). Among MetS components, average changes in HDL2-C/HDL3-C were associated with changes in WC and HDL-C. Average changes in HMW-Ad and the homeostasis model assessment of insulin resistance were significantly higher and lower, respectively, in the ≥0.5 HDL2-C/HDL3-C change group compared with those in the reference group. In addition, the average low-density lipoprotein cholesterol (LDL-C) gradually decreased as HDL2-C/HDL3-C increased. The average change in LDL-C was significantly lower in the 0 to ＜0.5 and ≥0.5 HDL2-C/HDL3-C change groups than in the reference group. Moreover, a ≥0.5 HDL2-C/HDL3-C change positively correlated with good lifestyle statuses in terms of smoking, physical activity, and alcohol consumption. CONCLUSION Changes in HDL2-C/HDL3-C inversely correlated with changes in WC, insulin resistance, and LDL-C and positively correlated with HMW-Ad and good lifestyle habits. Therefore, HDL2-C/HDL3-C changes comprise a useful marker for both MetS and atherogenic conditions in Japanese population.

Evaluation of Malondialdehyde Low-Density Lipoprotein Stratified by Low-Density Lipoprotein Cholesterol

BACKGROUND Malondialdehyde low-density lipoprotein (MDA-LDL) is a major form of oxidized LDL and considered to be more atherogenic than LDL. Information on major determinants of MDA-LDL and their association in subjects who are not under treatment for diabetes mellitus and dyslipidemia is limited. METHODS This study included 778 Japanese subjects who were not taking medication for diabetes mellitus and dyslipidemia. All subjects underwent an annual health examination that included MDA-LDL analysis. Study subjects were divided into four groups according to mean values of LDL-C and MDA-LDL, and the metabolic profile was compared. RESULTS LDL cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were mainly associated with MDA-LDL. When subjects were stratified based on LDL-C levels, small dense LDL-C and MDA-LDL levels increased as LDL-C levels increased. Comparison of the characteristics of study subjects in the same LDL-C level group revealed that subjects with high MDA-LDL showed high metabolic risk in all LDL-C groups, particularly notable in the group with LDL-C levels < 120 mg/dL. CONCLUSIONS Our data indicated that high LDL-C and low HDL-C levels were independently associated with high MDA-LDL. To prevent high MDA-LDL, it is important to lower LDL-C level as well as to increase HDL-C even in subjects with low LDL-C level by lifestyle modification.