Insulin Resistance In Japanese Research Articles

Association between alcohol consumption and incidence of impaired insulin secretion and insulin resistance in Japanese: The Saku study

AimsTo investigate the effect of alcohol consumption on impaired insulin secretion and insulin resistance in Japanese. MethodsThe participants in this 5-year cohort study were 2100 Japanese aged 30–74 years without type 2 diabetes mellitus, impaired insulin secretion, or insulin resistance who underwent a medical checkup including 75-g OGTT between April 2008 and March 2009 at Saku Central Hospital. Alcohol consumption was categorized as follows: non-drinker (0 g/week), light drinker (1–139 g/week in men and 1–69 g/week in women), moderate drinker (140–274 g/week in men and 70–139 g/week in women) and heavy drinker (≥275 g/week in men and ≥140 g/week in women). The hazard ratios (HRs) and 95% CIs among light to heavy drinkers for incidence of impaired insulin secretion (insulinogenic index ≤51.7) and insulin resistance (HOMA-IR ≥ 2.5), detected by an OGTT at the time of a follow-up medical checkup before the end of March 2014, were estimated by multivariable adjusted Cox proportional hazard models as reference values for non-drinkers. ResultsThere were 708 cases of impaired insulin secretion and 191 cases of insulin resistance. The HRs (95% CIs) for impaired insulin secretion in light, moderate and heavy drinkers were 1.16 (0.96–1.40), 1.35 (1.07–1.70) and 1.64 (1.24–2.16), respectively (P for trend <0.001). For insulin resistance, the HRs were 1.22 (0.84–1.76), 1.42 (0.91–2.22) and 1.59 (0.96–2.65), respectively (P for trend = 0.044). ConclusionAlcohol consumption was positively associated with the incidence of both impaired insulin secretion and insulin resistance.

Westernization of lifestyle affects quantitative and qualitative changes in adiponectin

BackgroundAlthough Japanese–Americans and native Japanese share the same genetic predispositions, they live different lifestyles, resulting in insulin resistance in Japanese–Americans. We investigated whether the quantitative and qualitative changes in adiponectin (APN) due to differences in lifestyle contribute to the development of insulin resistance.MethodsWe evaluated 325 native Japanese in Hiroshima, Japan and 304 Japanese–Americans in Los Angeles, the United States, who were aged between 30 and 70 years and underwent medical examinations between 2009 and 2010. All participants underwent a 75-g oral glucose tolerance test (OGTT) to assess their glucose tolerance. The insulin response to oral glucose load, the Matsuda index, total APN levels, and C1q-APN/total-APN ratios were compared between native Japanese and Japanese–Americans.ResultsCompared with the native Japanese, the Japanese–Americans had significantly lower Matsuda index and higher area under the curve values for serum insulin concentration during OGTT in the normal glucose tolerance (NGT) and impaired glucose tolerance (IGT) groups, but not in the diabetes mellitus (DM) group. Furthermore, the Japanese–Americans had significantly lower total APN levels and higher C1q-APN/total-APN ratios than the native Japanese in the NGT and IGT groups, but not in the DM group.ConclusionsThis study suggested that, in Japanese people, the westernization of their lifestyle might affect quantitative and qualitative changes in APN and induce insulin resistance.

Relationships between Composition of Major Fatty Acids and Fat Distribution and Insulin Resistance in Japanese.

Objective. The aim of this study was to evaluate the relationships between the composition of free fatty acids (FFAs) and metabolic parameters, including body fat distribution, in Japanese. Methods. The study subjects were 111 Japanese patients (54 males, 57 females). Metabolic parameters and visceral and subcutaneous fat areas as determined by CT scanning at the umbilical level were measured. Glucose tolerance test (GTT) was performed by administering 75 g glucose orally. Results. The percentage of linoleic acid (C18:2), the greatest constituent among FFAs, was negatively correlated with visceral fat area (r = −0.411, p < 0.0001), fasting glucose (r = −0.330, p < 0.0001), HbA1c (r = −0.231, p = 0.0146), and systolic blood pressure (r = −0.224, p = 0.0184). Linoleic acid percentage was also significantly negatively correlated with HOMA-IR (r = −0.416, p < 0.0001) by simple correlation. Based on the findings of OGTT, the 111 subjects were classified into three groups: 33 with normal glucose tolerance, 71 with impaired glucose tolerance (IGT), and 7 diabetic subjects. The percentage of serum linoleic acid in diabetic subjects was significantly lower than that in normal subjects. Conclusion. We conclude that serum linoleic acid level is negatively correlated with the accumulation of visceral fat in relation to a reduction of insulin resistance in Japanese subjects.

Distribution of the Matsuda Index in Japanese healthy subjects.

We investigated the cut-off point of the Matsuda Index in Japanese according to the guideline from the Clinical and Laboratory Standards Institute. A total of 1,596 subjects free from medications for diabetes mellitus, dyslipidemia and/or hypertension, and without cardiovascular diseases or chronic renal failure underwent a health check-up and oral glucose tolerance test (OGTT). We recruited 204 healthy reference individuals with normal glucose tolerance without obesity, any component of metabolic syndrome or elevated alanine aminotransferase. The Matsuda Index was calculated with 0- and 120-min data during OGTT. As the index was not normally distributed (P<0.001 by the Shapiro-Wilk test), the log-transformed value (P=0.876 by the Shapiro-Wilk test) was used. The mean±2 standard deviations were taken as the reference limits. The lower reference limit of the Matsuda Index was then calculated to be 4.3. Our result shows that a Matsuda Index <4.3 indicates the presence of insulin resistance in Japanese.

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/m(2) 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).

Association of gene polymorphism of the fat-mass and obesity-associated gene with insulin resistance in Japanese

It was reported that gene polymorphisms in the fat-mass and obesity-associated gene (FTO) were associated with obesity and diabetes in several genome-wide association studies. A recent report indicated that FTO-knockout mice exhibited phenotypes of skinny body shape and normal metabolic profiles. Thus, FTO could be important in metabolic disorders. The aim of this study was to clarify the role of single nucleotide polymorphisms (SNPs) in FTO in metabolic disorders such as hypertension, obesity, diabetes, dyslipidemia, insulin resistance and metabolic syndrome in the Japanese general population using data from a cohort study in Hokkaido, namely the Tanno-Sobetsu study. Written informed consent for the genetic analysis was obtained from each subject participating in the study. A total of 1514 subjects were genotyped by TaqMan PCR methods for three SNPs, rs9939609, rs1121980 and rs1558902, in FTO. Association analyses between the SNPs and metabolic parameters were performed. Although two SNPs, rs9939609 and rs1558902, were not significantly associated with hypertension, obesity, metabolic syndrome or any metabolic parameters, additive and recessive models of rs1121980 were strongly associated with plasma immunoreactive insulin (IRI) level and homeostasis model assessment insulin resistance (HOMA-IR), even after adjusting for confounding factors such as age, gender and body mass index. A haplotype of three SNPs was also significantly associated with IRI and HOMA-IR. One SNP, rs1121980, and a haplotype of three SNPs in FTO that contains this SNP, might be important in the progression of insulin resistance in Japanese subjects.

Association of Urinary Albumin Excretion with Insulin Resistance in Japanese Subjects: Impact of Gender Difference on Insulin Resistance

To investigate the relationship between homeostasis model assessment for insulin resistance (HOMA-R) and urinary albumin excretion in Japanese and clarify gender difference in albuminuria-related insulin resistance. The subject group consisted of 752 Japanese who had no history of diabetes, hypertension or dyslipidemia. After anthropometric examination, fasting blood samples were obtained to determine plasma glucose (FPG), lipids and HOMA-R. The urinary excretion of albumin in the first void urine was expressed as the creatinine ratio (ACR, mg/gCr). Estimated glomerular filtration rate (eGFR) was calculated from serum creatinine using the formula for Japanese. HOMA-R showed a significant correlation with ACR, and the correlation between HOMA-R and ACR was evident in the subjects with central obesity, whereas no significant correlation was found in the non-obese subjects. There was no correlation between HOMA-R and eGFR. HOMA-R increased according to the quintile of ACR and followed a significant trend. This association was obvious in males; however, in females there was no significant trend. Multiple regression analysis revealed that HOMA-R showed a significant correlation with age, waist circumference, blood pressure and serum triglyceride. In addition, ACR exhibited an independent association with HOMA-R. The association of HOMA-R and ACR was observed only in males, and was not present in females. Microalbuminuria is associated with insulin resistance in Japanese, where central obesity might play an essential role. This association is gender-specific suggesting the involvement of sex hormones in the pathogenesis of albuminuria-related insulin resistance.

Association between C-reactive Protein and Insulin Resistance in a Japanese Population: The Minoh Study

To investigate the association between C-reactive protein (CRP) and insulin resistance. This study included 1,624 Japanese participants (652 men and 972 women) aged 40 to 69 years who were non-diabetics or did not have medication for hypertension or dyslipidemia, a history of cardiovascular disease or CRP levels >10 mg/l. Serum CRP level, fasting glucose level, and fasting insulin level were measured, and the degree of insulin resistance was assessed using the homeostasis model assessment of insulin resistance (HOMA-IR). Categories of CRP were defined by the following tertiles: <0.25 mg/l, 0.25-0.59 mg/l, and > or = 0.60 mg/l. Elevated CRP levels were associated with increased fasting insulin levels, fasting glucose levels, and HOMA-IR in both men and women. Although the adjustment for body mass index in addition to age, cigarette smoking, and alcohol consumption attenuated the associations between CRP and fasting insulin, fasting glucose, and HOMA-IR, elevated CRP levels were associated with increased insulin levels and HOMA-IR in both sexes. Stratified analyses by CRP level and obesity showed that obesity status was associated with increased fasting insulin levels, fasting glucose levels, and HOMA-IR in both sexes and that fasting insulin levels, fasting glucose levels, and HOMA-IR were higher among obese individuals than among non-obese individuals at the same level of CRP. These results suggest a possible role of subclinical inflammation in insulin resistance and glucose intolerance in Japanese, but it only partly explains the link between obesity and impaired glucose homeostasis.

Variations in vitamin D-binding protein (group-specific component protein) are associated with fasting plasma insulin levels in Japanese with normal glucose tolerance.

The locus of the vitamin D-binding protein (DBP; also known as group-specific component protein or Gc) gene, chromosome 4q12, has been reported to be associated with glucose metabolism in several ethnic groups, including Pima Indians. We have recently reported the association of the DBP genotype with type 2 diabetes mellitus in Japan. The aim of this study was to investigate whether genetic variations of DBP have any influence on glucose metabolism without secondary effects of hyperglycemia or diabetes mellitus using 82 Japanese with normal glucose tolerance. The variations of the DBP gene (Gc 1F, 1S, and 2) were determined by PCR-restriction fragment length polymorphism. Fasting plasma insulin concentration and homeostasis model assessment, an index of insulin resistance, were significantly different based on the DBP genotype (P < 0.01 and P < 0.05, respectively). The people with Gc 1S-2 (5.73 +/- 2.57 microU/mL) and 1S-1S (5.30 +/- 3.46 microU/mL) had significantly higher fasting plasma concentrations than those with 1F-1F (2.84 +/- 1.67 microU/mL) (P < 0.01 and P < 0.03, respectively). There was no significant difference in plasma glucose concentration, body mass index, total cholesterol, triglyceride, and blood pressure. In conclusion, genetic variations of DBP are associated with insulin resistance in Japanese with normal glucose tolerance, which might contribute to the development of type 2 diabetes.

日本人および日系米人女性におけるアポE表現型と脂質代謝, インスリン抵抗性の関連

日本人および日系米人女性におけるアポE表現型と脂質代謝, インスリン抵抗性の関連