Non-obese Japanese Research Articles

Association of decrease in carbohydrate intake with reduction in abdominal fat during 3-month moderate low-carbohydrate diet among non-obese Japanese patients with type 2 diabetes

ObjectiveThe effectiveness of a moderate low-carbohydrate diet (M-LCD) has been demonstrated in terms of glycemic control, body weight and serum lipid profiles. We investigated the effect of a 3-monthM-LCD on visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT), and examined an association between decrease in carbohydrate intake and reduction in abdominal fat among patients with Type 2 diabetes mellitus (T2DM). MethodsSeventy-six patients (45 men and 31 women; mean age±SD: 59.5±11.1years) with T2DM were instructed to follow an M-LCD for 3months. We assessed abdominal fat distribution using computed tomography and macronutrient intakes from 3-day dietary records at baseline and after 3months. ResultsThe patients complied well with the M-LCD – %carbohydrate: %fat: %protein at baseline and after 3months were 51:27:15 and 41:33:18 in men and 54:27:16 and 42:37:19 in women, respectively. VAT and SAT significantly decreased during the 3months (P for time <0.001 for both). Decrease in carbohydrate intake (g/day) and %carbohydrate were correlated with decrease (%) in VAT. The correlations were significant in men (Spearman correlation coefficient r=0.469 for carbohydrate intake (g) and r=0.402 for %carbohydrate) but not in women (r=0.269 and 0.278, respectively). The correlations in men remained significant in multiple regression analysis adjusted for age and changes in energy intake. ConclusionsIn men, decrease in carbohydrate intake was significantly correlated with VAT loss during a 3-monthM-LCD, independently of reduction in energy intake.

The association between impaired proinsulin processing and type 2 diabetes mellitus in non-obese Japanese individuals.

We aimed to examine the association between impaired proinsulin processing in pancreatic beta cells and type 2 diabetes mellitus in non-obese Japanese patients. Participants were divided into groups for normal glucose tolerance, prediabetes, and type 2 diabetes based on the oral glucose tolerance test (OGTT). Activities of prohormone convertase (PC) 1/3 and PC2 in fasting states were estimated. Multiple regression analysis was undertaken to ascertain if alteration of the activities of these enzymes contributes to the development of impaired glucose tolerance by comparison with HOMA-β and the oral disposition index (DI(O)). Overall, 452 subjects were included. PC1/3 activity tended to decrease in type 2 diabetes compared with normal glucose tolerance. PC2 activity showed no difference among the three groups. Decreased estimated PC1/3 activity was significantly associated with type 2 diabetes after adjustment for sex, age, creatinine, triglycerides, HOMA-β and DI(O). Odds ratios (95% CI) of PC1/3, HOMA-β, and DI(O) were 2.16 (1.12-4.19), 3.44 (1.82-6.52) and 14.60 (7.87-27.11), respectively. Furthermore, decreased PC1/3(≤1.7) combined with decreased HOMA-β (≤30) had a sensitivity of 73% and specificity of 62%. Decreased PC1/3 activity may be a useful measurement of beta-cell function alongside decreased HOMA-β or DI(O). A combined decrease in estimated fasting PC1/3 activity and HOMA-β measurement led to suspicion of type 2 diabetes in the non-obese Japanese population studied.

A Case of Obstructive Sleep Apnea Syndrome, whose Sole Complaint of Night Sweat was Eliminated with Continuous Positive Airway Pressure

A 69-year-old non-obese Japanese man with obstructive sleep apnea syndrome (OSAS) complaining solely about night sweat was treated successfully with continuous positive airway pressure. Nocturnal sweating of a common symptom of OSAS is also caused by drugs/alcohol/heroin, malignancies, infections, gastro-esophageal reflux, and endocrine/rheumatologic diseases. Family physicians should include OSAS in the differential diagnosis of this symptom.

Impact of abdominal and epicardial fat on the association between plasma adipocytokine levels and coronary atherosclerosis in non-obese patients

Objective: Ectopic fat accumulation is associated with coronary artery disease. Visceral adipose tissue has paracrine and systemic effects and is a source of adipocytokines. It has been implicated in the pathogenesis of coronary atherosclerosis; however, nothing is known about whether increases in epicardial fat have the same effect on coronary atherosclerosis as increases in abdominal visceral fat. Methods: We examined 216 consecutive patients suspected to have coronary artery disease. Individuals with acute coronary syndrome and inadequate computed tomography (CT) imaging were excluded. We enrolled 164 patients (65 ± 10 years old; 70% men; body mass index [BMI], 23.8 ± 3.6 kg/m2). The plasma concentrations of adiponectin, interleukin-6 (IL-6), plasminogen activator inhibitor-1, and vascular endothelial growth factor were measured. The characteristics of coronary plaque, abdominal visceral fat area, and epicardial fat volume (EFV) were determined by 64-slice CT imaging. Results: EFV was greater in subjects with noncalcified plaque than in those with no plaque or with calcified plaque (126 ± 39 mL vs. 98 ± 34 mL and 97 ± 45 mL, respectively; P = 0.010). EFV was significantly correlated with BMI, triglycerides, and the triglyceride/high-density lipoprotein cholesterol ratio (r = 0.51, 0.19, and 0.20, respectively) but not with plasma levels of adipocytokines. The plasma adiponectin and IL-6 concentration was significantly correlated with abdominal visceral fat area in coronary plaque patients (r = −0.49 and 0.20). Conclusions: In non-obese Japanese patients, epicardial fat may have unique mechanisms affecting the development of coronary atherosclerosis, which is different from abdominal visceral fat.

Clinical features of fatty liver in nonobese Japanese without regular alcohol intake

The clinical features of fatty liver (FL) detected by ultrasonography (US) in nonobese and diabetes mellitus type 2 are not yet understood, and metabolic syndrome (MetS) has become an important health issue throughout the world. We investigated the clinical features of fatty liver (FL) in nonobese patients. From 2008 to 2010, 2192 Japanese patients underwent a medical checkup at our hospital. Obesity was defined as a body mass index (BMI) ≥25 kg/m2, while normal waist circumference (WC) was defined as <85 cm in males and <90 cm in females. FL was determined in 958 after excluding subjects who regularly drank alcohol (≥20 g/day), who were obese, or had an abnormal WC. We evaluated the clinical backgrounds [biological and lipid examination results, fasting blood sugar, hemoglobin A1c, insulin, HOMA-R, blood pressure (BP), BMI, and medical interviews]. BP, triglyceride, and HOMA-R levels were significantly elevated in nonobese with normal WC with FL (males: 122/78 vs. 120/76 mmHg, 161.5 vs. 105.5 mg/dl, 1.9 vs. 1.3, respectively; females: 120/73 vs. 116/71 mmHg, 115.2 vs. 82.0 mg/dl, 1.7 vs. 1.3, respectively). Both males and females with FL had a past history of increased body weight over 10 kg after reaching the age of 20 years as compared to those without FL (P < 0.01 and P = 0.04, respectively). Nonobese subjects with normal WC and FL had significantly higher BP, triglyceride, and HOMA-R levels than nonobese subjects with normal WC without FL. Lifestyle instruction should be given to such individuals to prevent insulin resistance and progression to MetS.

Resting heart rate predicts metabolic syndrome in apparently healthy non-obese Japanese men

Autonomic nervous dysfunction is considered to be one of the mechanisms of metabolic syndrome (MetS). The aim of this study is to investigate whether resting heart rate, a marker of autonomic nervous dysfunction, is a predictor of MetS in apparently healthy non-obese [body mass index (BMI) <25 kg/m(2)] Japanese men. This is an observational study through 3 years in apparently healthy Japanese 1,265 men and 793 women without MetS and with no history of cardiovascular disease and no use of antihypertensive, antidiabetic, or antihyperlipidemic medication at baseline. Hazard ratios (HRs) of incident MetS were calculated for each 1 SD increase in heart rate stratified by gender and obesity. Incidence of MetS for each tertile of heart rate and HRs of MetS for the highest tertile (T3) compared with the lowest tertile (T1) were calculated stratified by gender and obesity. The HRs [95% confidence intervals (CIs)] of MetS for each 1 SD increase in heart rate were 1.319 (1.035-1.681) (p = 0.025) in non-obese men, 1.172 (0.825-1.665) (p = 0.377) in obese men, 1.115 (0.773-1.608) (p = 0.560) in non-obese women, and 1.401 (0.944-2.078) (p = 0.094) in obese women adjusted for BMI, age, smoking, alcohol drinking, and physical activity. The HRs (95% CIs) of MetS for T3 were 2.138 (1.071-4.269) (p = 0.031) in non-obese men and 1.341 (0.565-3.180) (p = 0.506) in obese men adjusted for pre-existing five components of MetS, age, smoking, alcohol drinking, and physical activity. In conclusion, an increase in resting heart rate was a significant predictor of MetS in non-obese Japanese men.

Kir6.2 E23K polymorphism is related to secondary failure of sulfonylureas in non‐obese patients with type 2 diabetes

The Kir6.2 E23K polymorphism was studied with a special reference to secondary sulfonylurea (SU) failure in non-obese patients with type2 diabetes. We recruited 278 non-obese (body mass index ≤30.0kg/m(2)) Japanese patients with type2 diabetes who had a history of SU treatment (for 11.2±6.3years) and compared the frequency of the secondary SU failure among the genotypes of the polymorphism. Genotyping of the Kir6.2 E23K was carried out by polymerase chain reaction-restriction fragment length polymorphism. The genotype frequencies of the polymorphism were similar to those previously reported in Japanese patients with type2 diabetes. The frequency with which patients deteriorated into secondary SU failure was significantly higher in those with the KK genotype than those with EE or EK genotypes. Among 214 patients who eventually received insulin therapy because of secondary SU failure, the period of SU treatment in those with the KK genotype was significantly shorter than those with the EE or EK genotype, although the period from diagnosis to the start of SU treatment was not significantly different. These data suggest that the Kir6.2 E23K polymorphism is related to the acceleration of secondary SU failure in non-obese Japanese patients with type2 diabetes.

Circulating TNF receptor 2 is associated with the development of chronic kidney disease in non-obese Japanese patients with type 2 diabetes

AimsChronic low-grade inflammation and/or obesity are suggested to induce chronic kidney disease (CKD) in patients with type 2 diabetes. This cross-sectional study was performed to investigate the relationship between inflammatory biomarkers and CKD in non-obese patients with type 2 diabetes. Methods106 non-obese Japanese patients with type 2 diabetes were recruited for the measurement of GFR, TNF, HMW adiponectin, leptin, hsCRP and some variables including urinary albumin. BMI, serum creatinine, and urinary albumin levels were 22.2±0.2kg/m2 (17.1–24.9kg/m2), 0.76±0.02mg/dl (0.39–1.38mg/dl), 40.4±4.3mg/gCr (1.6–195.0mg/gCr), respectively. They were stratified into two groups based on the value of eGFR: low eGFR (eGFR<60ml/min/1.73m2) and normal eGFR (eGFR>60ml/min/1.73m2). Logistic regression analysis was used for statistical analysis. ResultsWhereas univariate logistic regression analysis showed that gender, diabetes duration, triglyceride, HDL cholesterol, uric acid, urinary albumin, and soluble TNF receptors (sTNF-R1, sTNF-R2) are associated with the development of stage 3 CKD, multivariate logistic regression analysis revealed that sTNF-R2 (Odds ratio 1.003, 95% confidence interval 1.000 to 1.005, P=0.030) showed significant associations with the development of stage 3 CKD. ConclusionsCirculating TNF receptor 2 is an independent risk factor for CKD in non-obese Japanese patients with type 2 diabetes.

The combined effect of the T2DM susceptibility genes is an important risk factor for T2DM in non-obese Japanese: a population based case-control study

BackgroundType 2 diabetes mellitus (T2DM) is a complex endocrine and metabolic disorder. Recently, several genome-wide association studies (GWAS) have identified many novel susceptibility loci for T2DM, and indicated that there are common genetic causes contributing to the susceptibility to T2DM in multiple populations worldwide. In addition, clinical and epidemiological studies have indicated that obesity is a major risk factor for T2DM. However, the prevalence of obesity varies among the various ethnic groups. We aimed to determine the combined effects of these susceptibility loci and obesity/overweight for development of T2DM in the Japanese.MethodsSingle nucleotide polymorphisms (SNPs) in or near 17 susceptibility loci for T2DM, identified through GWAS in Caucasian and Asian populations, were genotyped in 333 cases with T2DM and 417 control subjects.ResultsWe confirmed that the cumulative number of risk alleles based on 17 susceptibility loci for T2DM was an important risk factor in the development of T2DM in Japanese population (P < 0.0001), although the effect of each risk allele was relatively small. In addition, the significant association between an increased number of risk alleles and an increased risk of T2DM was observed in the non-obese group (P < 0.0001 for trend), but not in the obese/overweight group (P = 0.88 for trend).ConclusionsOur findings indicate that there is an etiological heterogeneity of T2DM between obese/overweight and non-obese subjects.

Insulin-secretion capacity in normal glucose tolerance, impaired glucose tolerance, and diabetes in obese and non-obese Japanese patients.

Aims/Introduction: Pronounced reduction of insulin secretion in response to a rise in glucose level has been reported in Japanese patients compared with Caucasian patients, but the mean body mass index (BMI) is also lower in Japanese patients. As BMI is a determinant of insulin secretion, we examined insulin-secretion capacity in obese and non-obese Japanese patients. Using the oral glucose tolerance test (OGTT), we estimated the insulin-secreting capacity in obese (BMI ≥ 25) and non-obese (BMI < 25) Japanese patients, including 1848 patients with normal glucose tolerance (NGT), 321 patients with impaired glucose tolerance (IGT) and 69 diabetes (DM) patients. The insulinogenic index (I.I.), calculated by dividing the increment in serum insulin by the increment in plasma glucose from 0 to 30 min during OGTT, decreased from NGT to IGT and to DM in patients with and without obesity. In patients with NGT, IGT and DM, the I.I. values of obese patients were higher than those of the non-obese patients. The peak of insulin concentration in OGTT appeared at 60 min in NGT and at 120 min in IGT in both obese and non-obese patients, but in DM it was observed at 120 min in obese patients and at 60 min in non-obese patients. These results show that early-phase insulin secretion in obese Japanese patients is higher than in non-obese patients in all stages of glucose tolerance, and delayed insulin-secretion capacity is also conserved in obese Japanese patients, even in IGT and DM, which is similar to Caucasian patients. (J Diabetes Invest, doi:10.1111/j.2040-1124.2011.00180.x, 2011).

Impaired glucose metabolism in Japanese patients with acromegaly is restored after successful pituitary surgery if pancreatic β-cell function is preserved

Impaired glucose metabolism is common in acromegaly, but it is not clear how glucose metabolism is impaired or what predicts its restoration after cure of the disease. To identify factors involved in the impairment of glucose metabolism in acromegaly, we evaluated clinical parameters before and immediately after surgical cure of the disease. We retrospectively analyzed clinical data of 92 consecutive Japanese patients with acromegaly who underwent successful pituitary surgery. Patients who had received medical therapy for acromegaly or insulin treatment for diabetes were excluded. We evaluated insulin resistance (IR) and pancreatic β-cell function in addition to GH and IGF1 levels before and after surgery. Results In this study of Japanese patients with acromegaly, average body mass index (BMI) was 23.4, and no patient had a BMI>30. IR was involved in the impairment of glucose metabolism, which was restored upon surgical cure of acromegaly if β-cell function was preserved. Insufficient β-cell function did not improve after normalization of GH/IGF1 and was associated with impaired glucose metabolism before and after surgery. of receiver operating characteristic analysis of preoperative clinical parameters suggest that insulinogenic index (IGI) >0.50 best predicts restoration of normal glucose metabolism upon cure of acromegaly in Japanese patients. IR impairs glucose metabolism in acromegaly. Once β-cell function is impaired, abnormal glucose metabolism persists even after cure of acromegaly. IGI>0.50 indicates that β-cell function is preserved in non-obese Japanese patients with acromegaly.

Normal Response of Active GLP-1 Level like Substances to Test Meal in Non-Obese Type 2 Diabetic Japanese Patients with Complications and Receiving Treatments

Background: Study has shown no significant differences in basal and postprandial plasma active glucagon-like peptide-1 (p-active GLP-1) levels following test meal (TM) between complication- and treatment-naive non-obese Japanese patients with type 2 diabetes (T2DM) and controls. Methods: In non-obese Japanese patients with T2DM (n=23, group 1) and healthy individuals as control (n=13, group 2), blood levels of plasma glucose (PG), serum insulin (s-IRI), serum C-peptide (s-CPR) and p-active GLP-1 like substances (p-active GLP-1-S) were measured 0, 30, and 60 min after TM (520-560 kcal. 23% fat, 60% carbohydrate and 17% protein). HbA1c levels were also measured in the groups. Patients with mean of 9.2 years disease had various complications and treatment with diet, exercise and/or oral medical drugs except incretin-related drugs for hyperglycemia. Results: There was no significant difference in mean of sex, age, or BMI between groups. Means of HbA1c and basal and postprandial PG with area under curve (AUC), and HOMA-R were significantly higher in group 1 than in group 2. Means of HOMA-β and insulinogenic index after ingestion of TM were significantly lower in group 1 than in group 2. However, there were no significant differences in means of basal and postprandial with AUC levels of s-IRI, s-CPR and p-active GLP-1-S levels between groups. Conclusion: These results indicated that a response of p-active GLP-1-S to TM in non-obese Japanese patients with T2DM associated with a long duration of disease, various complications and various treatments with except incretin-related drugs was similar to those in non-obese healthy individuals.

Dietary Patterns Only Partially Explain the Effect of Short Sleep Duration on the Incidence of Obesity

To investigate whether dietary patterns explain the possible association between short sleep duration and obesity. Longitudinal study. Annual health checkup at a Japanese workplace over a 4-year period from 1994-1995 (baseline) to 1998-1999 (follow-up). Nonobese Japanese male workers aged 40 to 59 years (n = 2632). Trained health professionals conducted a questionnaire-based survey. Preference for fatty food, skipping breakfast, and eating out were significantly associated with short sleep duration. Snacking and preference for fatty food significantly predicted the incidence of obesity, which was defined as a body mass index of at least 25 kg/m2. Hierarchic logistic regression analyses were conducted to test the significance of the association between sleep duration and the incidence of obesity, before and after controlling for covariates, including dietary patterns (preference for fatty food, skipping breakfast, snacking, and eating out). Participants who slept less than 6 hours were compared with those who slept 7.0 to 7.9 hours. The odds ratio for the incidence of obesity was 2.55 (95% confidence interval [CI] 1.48, 4.42; trend P = 0.007) with covariate adjustment, except for dietary patterns, and 2.46 (95% CI 1.41, 4.31; trend P = 0.011) with complete adjustment, including dietary patterns. Preference for fatty food, skipping breakfast, snacking, and eating out only partially explained the effects of short sleep duration on the incidence of obesity, suggesting that other factors, including physiologic mechanisms, may largely explain the sleep-obesity association.

Palatinose-blended sugar compared with sucrose: different effects on insulin sensitivity after 12 weeks supplementation in sedentary adults

Background: We investigated the effects of daily palatinose intake on the risk factors of metabolic syndrome in sedentary non-obese Japanese adults.Methods: Japanese adults (40 females and 10 males, age: 53 ± 9 years, range: 31–72 years old) were randomized into two groups for a double-blind, placebo-controlled intervention study and given either 40 g/day palatinose-blended sugar (PS group) or 40 g/day sucrose (S group) in their diet for 12 weeks.Results: After the intervention, the insulin resistance index (HOMA-IR) had significantly decreased only in the PS group; the inter-group difference was significant at P = 0.006. Although the S group showed a significant increase in the leptin concentration and the systolic blood pressure, the PS group showed no significant changes; the inter-group differences were significant at P = 0.018 and P = 0.037, respectively.Conclusion: Palatinose intake possibly improves insulin sensitivity when compared with sucrose intake.

Similar incretin secretion in obese and non-obese Japanese subjects with type 2 diabetes

Incretin secretion and effect on insulin secretion are not fully understood in patients with type 2 diabetes. We investigated incretin and insulin secretion after meal intake in obese and non-obese Japanese patients with type 2 diabetes compared to non-diabetic subjects. Nine patients with type 2 diabetes and 5 non-diabetic subjects were recruited for this study. Five diabetic patients were obese (BMI ⩾ 25) and 4 patients were non-obese (BMI < 25). In response to a mixed meal test, the levels of immunoreactive insulin during 15–90 min and C-peptide during 0–180 min in non-obese patients were significantly lower than those in obese patients. Total GLP-1 and active GIP levels showed no significant difference between obese and non-obese patients throughout the meal tolerance test. In addition, there were no significant differences between diabetic patients and non-diabetic subjects. In conclusion, incretin secretion does not differ between Japanese obese and non-obese patients with type 2 diabetes and non-diabetic subjects.

High Blood Pressure in Obese and Nonobese Japanese Children: Blood Pressure Measurement is Necessary Even in Nonobese Japanese Children

BackgroundAlthough the prevalences of obesity and hypertension (HT) are increasing in children, there have been few epidemiological studies of HT in Japanese children. We evaluated the prevalences of HT and high-normal blood pressure (HNBP), and examined the relationship between blood pressure (BP) and body mass index (BMI), in Japanese children.MethodsThe subjects of this study were 2420 children living in the town of Ina, Saitama Prefecture, Japan during the period from 2006 through 2008. Body height, weight, and BP were measured. HT and HNBP were defined according to the HT criteria for Japanese children. Children with HNBP or HT were defined as having high blood pressure (HBP).ResultsThe prevalences of HBP were 15.9% and 15.8% in fourth-grade boys and girls, respectively, and 11.1% and 10.8% in seventh-grade boys and girls, respectively. Irrespective of sex or grade level, a higher BMI was associated with a higher prevalence of HBP (P < 0.001). When compared with the <50th percentile BMI category, the crude odds ratios (ORs) were statistically significant for the 75th to 84th percentile category in fourth-grade boys (OR: 4.54, 95% CI: 2.36–8.76), the ≥95th percentile in fourth-grade girls (13.29, 5.93–29.77), the 85th to 94th percentile (3.16, 1.46–6.84) in seventh-grade boys, and the ≥95th percentile (7.96, 3.18–19.93) in seventh-grade girls.ConclusionsBMI was associated with HBP in Japanese school children. In addition, some children in the lower BMI categories also had HBP.

1229 A phase I study of continuous and intermittent schedules of lapatinib in combination with vinorelbine in solid tumors

The aim of the present study was to investigate the relationship between insulin resistance and tumor necrosis factor α (TNF-α) as well as soluble TNF receptors (sTNF-R), body mass index (BMI), leptin, adiponectin, and serum lipid profile including triglycerides in nonobese Japanese patients with type 2 diabetes.A total of 88 nonobese Japanese type 2 diabetic patients were studied. The duration of diabetes was 11.0 ± 0.8 years. In conjunction with BMI, glycosylated hemoglobin (HbA1c), fasting concentrations of plasma glucose, serum lipids (triglycerides, high-density lipoprotein cholesterol, and total cholesterol), serum leptin, serum adiponectin, serum TNF-α, and soluble TNF receptors (sTNF-R1 and sTNF-R2) were also measured. Insulin resistance was estimated by the insulin resistance index of homeostasis model assessment.Insulin resistance was positively correlated with BMI, triglycerides, leptin, and total cholesterol and negatively correlated with adiponectin and high-density lipoprotein cholesterol. In contrast, insulin resistance was not associated with TNF-α, nor sTNF-R (sTNF-R1 and sTNF-R2) in our diabetic patients. There was no significant relationship between the 3 measures of TNF-α system (TNF-α, sTNF-R1, and sTNF-R2) and BMI, serum triglycerides, leptin, or adiponectin in these patients.From these results, it can be concluded that peripheral levels of TNF-α system activity are not a major factor responsible for insulin resistance in nonobese Japanese type 2 diabetic patients.

Trp64Arg Polymorphism in Beta3-Adrenergic Receptor Gene Is Associated with Decreased Fat Oxidation Both in Resting and Aerobic Exercise in the Japanese Male

The purpose of our study was to investigate whether the Trp64Arg polymorphism in β3-AR gene and the −3826A/G polymorphism in the UCP1 gene were associated with the reduction in energy expenditure and fat oxidation both in resting and aerobic exercise in Japanese. Eighty-six nonobese young healthy Japanese were recruited. Energy expenditure was measured using indirect calorimetry. The subjects performed an aerobic exercise program at 60% of their maximal heart rate for 30 minutes. The level of fat oxidation at rest and aerobic exercise of the male subjects with Trp/Arg of the β3-AR gene was significantly lower than that of the Trp/Trp genotype. No difference in FO0−30 was observed in the female subjects. There was no association between UCP-1 polymorphism and energy expenditure during aerobic exercise. It was revealed that the Trp64Arg polymorphism in β3-AR gene is associated with reduction of fat oxidation both in resting and aerobic exercise in healthy, young Japanese males.

A Common P2 Promoter Polymorphism of the Hepatocyte Nuclear Factor-4.ALPHA. Gene Is Associated with Insulin Secretion in Non-Obese Japanese with Type 2 Diabetes

Heterozygous mutations of the hepatocyte nuclear factor (HNF)-4alpha gene cause a particular form of maturity-onset diabetes of the young (MODY1). Recent genetic studies have shown that single nucleotide polymorphisms (SNPs) of the beta-cell type P2 promoter of the HNF-4alpha gene are associated with type 2 diabetes in some populations. In the Japanese population, a haplotype consisting of two SNPs (rs1884614 and rs2144908) in the P2 promoter region is reported to show a significant association with type 2 diabetes. Both rs1884614 and rs2144908 were genotyped in 349 type 2 diabetic patients and 203 non-diabetic controls. The relation of these SNPs to clinical characteristics was also examined in the diabetic subjects. There were no differences in the genotype distribution of the two SNPs between the control and diabetic subjects, and the haplotype distribution was also similar in the two groups. However, the rs1884614 T/T genotype was significantly associated with a smaller area under the plasma insulin curve (AUC) during the OGTT in non-obese (BMI <25 kg/m(2)) patients (p=0.0272; adjusted for age and sex). SNP rs1884614 in the P2 promoter region of the HNF-4alpha gene may influence insulin secretion in non-obese Japanese subjects with type 2 diabetes.

Association of novel promoter single nucleotide polymorphisms in vasopressin V1a receptor gene with essential hypertension in nonobese Japanese

We studied the association between four novel single nucleotide polymorphisms (SNPs) in the promoter region of V1aR gene and essential hypertension in 620 Japanese subjects (365 hypertensives and 255 healthy). A significant association was found between one of the genotypes and alleles at SNP -6951 and hypertension in a subsample of nonobese individuals. This association demonstrated an independent risk for nonobese hypertension.