Association of scan frequency with CGM-derived metrics and influential factors in adults with type 1 diabetes mellitus.

Introduction: This study aimed to investigate the association between scan frequency and intermittently scanned continuous glucose monitoring (isCGM) metrics and to clarify the factors affecting scan frequency in adults with type 1 diabetes mellitus (T1D). Methods: We enrolled adults with T1D who used FreeStyle® Libre. Scan and self-monitoring of blood glucose (SMBG) frequency and CGM metrics from the past 90-day glucose data were collected. The receiver operating characteristic curve was plotted to obtain the optimal cutoff values of scan frequency for the target values of time in range (TIR), time above range (TAR), and time below range (TBR). Results: The study was conducted on 211 adults with T1D (mean age, 50.9 ± 15.2 years; male, 40.8%; diabetes duration, 16.4 ± 11.9 years; duration of CGM use, 2.1 ± 1.0 years; and mean HbA1c, 7.6 ± 0.9%). The average scan frequency was 10.5 ± 3.3 scan/day. Scan frequency was positively correlated with TIR and negatively correlated with TAR, although it was not significantly correlated with TBR. Scan frequency was positively correlated with the hypoglycemia fear survey-behavior score, while it was negatively correlated with some glycemic variability metrics. Adult patients with T1D and good exercise habits had a higher scan frequency than those without exercise habits. The AUC for > 70% of the TIR was 0.653, with an optimal cutoff of 11 scan/day. Conclusions: In real-world conditions, frequent scans were linked to improved CGM metrics, including increased TIR, reduced TAR, and some glycemic variability metrics. Exercise habits and hypoglycemia fear-related behavior might affect scan frequency. Our findings could help healthcare professionals use isCGM to support adults with T1D.Clinical Trial Registry No. UMIN000039376.

Association of Impaired Awareness of Hypoglycemia with Driving Safety and Hypoglycemia Problem-solving Abilities among Patients with Type 1 Diabetes in Japan: The PR-IAH Study.

Objective Patients with type 1 diabetes (T1D) and impaired awareness of hypoglycemia (IAH) are at an elevated risk of experiencing automobile accidents. We therefore investigated the association of IAH with driving safety and hypoglycemia problem-solving abilities in adults with T1D. Methods This cross-sectional survey used Gold's method in adult patients with T1D at the National Hospital Organization (NHO) Hospital from February 14, 2020, to October 31, 2021. The participants were divided into control and IAH groups. The data included information on demographics, worries and distress regarding hypoglycemia, hypoglycemia problem-solving abilities, and adverse driving events. Patients We enrolled 233 participants (mean age: 48.5±12.8 years old, mean hemoglobin A1c level: 7.6%±0.9%) from NHO collaborating centers in Japan. Results Among a total of 233 participants (mean age: 48.5±12.8 years old, mean hemoglobin A1c level: 7.6%±0.9%), the prevalence rate of IAH was 11.6% [95% confidence interval (CI): 7.8-16.4%]. IAH was significantly associated with near-miss car accidents (odds ratio: 5.41; 95% CI:1.64-17.80). Diabetic peripheral neuropathy was associated with an increased risk of IAH, while treatment with continuous subcutaneous insulin infusion was not associated with a decreased risk of IAH. The average hypoglycemia problem-solving perception, detection control, and seeking preventive strategies scores in the IAH group were significantly reduced compared with those in the control group. Conclusion IAH was associated with an increased risk of near-miss car accidents among adults with T1D. Furthermore, good hypoglycemia problem-solving abilities were associated with a decreased risk of IAH.

The Effect of a mHealth App (KENPO-app) for Specific Health Guidance on Weight Changes in Adults With Obesity and Hypertension: Pilot Randomized Controlled Trial.

BACKGROUND: Commercial smartphone apps that promote self-monitoring of weight loss are widely available. The development of disease-specific apps has begun, but there is no app for specific health guidance (SHG) to prevent metabolic syndrome, type 2 diabetes, and cardiovascular diseases in middle-aged adults in Japan. OBJECTIVE: This study aimed to determine the efficacy of an SHG mobile health app in facilitating weight loss in Japanese adults with obesity and hypertension. METHODS: In a 12-week, statistician-blinded, randomized parallel controlled trial, 78 overweight and obese men aged 40-69 years were assigned in a 1:1 ratio to either the usual support plus KENPO-app group (intervention group) or the active control group. KENPO-app (release April 10, 2019; OMRON Healthcare Co., Ltd.) was developed by the study team and focus groups and uses behavior change techniques (ie, self-monitoring and goal-setting theory). This app was developed for SHG based on the four specific health checkups and guidance system in Japan: (1) focusing primarily on achieving the target (weight loss of ≥2 kg); (2) assessing healthy eating, exercise habits, smoking habits, relaxation, and self-weighing; (3) providing information on the results of specific health checkups; and (4) starting an intervention period of 6 months with the interim assessment at 3 months. The initial assessment explored the following: personality traits (4 types), health checkup data concerns (10 items), symptom concerns (10 items), and the aim of the intervention (weight loss, improving fitness, symptoms, laboratory data). Chatbot-supported health information on health and health behavior was selected from 392 quizzes based on app data and was provided to participants. The KENPO-app had chatbot-supported feedback and information provision combined with a self-monitoring tool (weight, steps, and blood pressure). Data on active exercise, healthy eating, and healthy lifestyle habits were obtained using a web-based self-administered questionnaire at baseline and 12 weeks. RESULTS: The trial's retention rate was 95% (74/78). The adherence to daily self-weighing, wearing the pedometer, and blood pressure monitoring in the KENPO-app group was significantly higher than those in the active control group. Compared with the active control group, the median body weight and BMI of the intervention group significantly decreased at 3 months (-0.4, IQR -2.0 to 0.6 kg vs -1.1, IQR -2.7 to -0.5 kg; P=.03; -0.1, IQR -0.6 to 0.3 kg vs -0.4, IQR -0.8 to -0.2 kg; P=.02, respectively). The intervention increased the percentage of participants who self-reported taking ≥8000 steps, eating vegetables before rice, eating slowly, and relaxing. Personality traits were associated with the degree of weight loss in the intervention group. CONCLUSIONS: The SHG-specific KENPO-app was feasible and induced modest but significant weight loss in adults with obesity. TRIAL REGISTRATION: University Hospital Medical Information Network Center UMIN000046263; https://tinyurl.com/bderys3b.

Protective and risk factors of impaired awareness of hypoglycemia in patients with type 1 diabetes: a cross-sectional analysis of baseline data from the PR-IAH study.

BACKGROUND: Hypoglycemia in type 1 diabetes (T1D) is associated with mortality and morbidity, especially when awareness of hypoglycemia is impaired. This study aimed to investigate the protective and risk factors for impaired awareness of hypoglycemia (IAH) in adults with T1D. METHODS: This cross-sectional study enrolled 288 adults with T1D (mean age, 50.4 ± 14.6 years; male, 36.5%; diabetes duration, 17.6 ± 11.2 years; mean HbA1c level, 7.7 ± 0.9%), who were divided into IAH and non-IAH (control) groups. A survey was conducted to assess hypoglycemia awareness using the Clarke questionnaire. Diabetes histories, complications, fear of hypoglycemia, diabetes distress, hypoglycemia problem-solving abilities, and treatment data were collected. RESULTS: The prevalence of IAH was 19.1%. Diabetic peripheral neuropathy was associated with an increased risk of IAH (odds ratio [OR] 2.63; 95% confidence interval [CI] 1.13-5.91; P = 0.014), while treatment with continuous subcutaneous insulin infusion and hypoglycemia problem-solving perception scores were associated with a decreased risk of IAH (OR, 0.48; 95% CI, 0.22-0.96; P = 0.030; and OR, 0.54; 95% CI, 0.37-0.78; P = 0.001, respectively). There was no difference in continuous glucose monitoring use between the groups. CONCLUSION: We identified protective factors in addition to risk factors for IAH in adults with T1D. This information may help manage problematic hypoglycemia. TRIAL REGISTRATION: University hospital Medical Information Network (UMIN) Center: UMIN000039475). Approval date 13 February 2020.

Factors associated with hemoglobin glycation index in adults with type 1 diabetes mellitus: The FGM-Japan study.

AIMS/INTRODUCTION: The discrepancy between HbA1c and glucose exposure may have significant clinical implications; however, the association between the hemoglobin glycation index (HGI) and clinical parameters in type 1 diabetes remains controversial. This study aimed to find the factors associated with HGI (laboratory HbA1c - predicted HbA1c derived from the continuous glucose monitoring [CGM]). MATERIALS AND METHODS: We conducted a cross-sectional study of adults with type 1 diabetes (n = 211, age 50.9 ± 15.2 years old, female sex = 59.2%, duration of CGM use = 2.1 ± 1.0 years). All subjects wore the CGM for 90 days before HbA1c measurement. Data derived from the FreeStyle Libre sensor were used to calculate the glucose management indicator (GMI) and glycemic variability (GV) parameters. HGI was defined as the difference between the GMI and the laboratory HbA1c levels. The participants were divided into three groups according to the HGI tertile (low, moderate, and high). Multivariate regression analyses were performed. RESULTS: The female sex ratio, HbA1c, and % coefficient of variation (%CV) significantly increased over the HGI tertile, while eGFR and Hb decreased over the HGI tertile. In multivariate analysis, the factors associated with HGI were %CV and eGFR, after adjusting for HbA1c level and sex (R2  = 0.44). CONCLUSIONS: This study demonstrated that HGI is associated with female sex, eGFR, and some glycemic variability indices, independently of HbA1c. Minimizing glycemic fluctuations might reduce HGI. This information provides diabetic health professionals and patients with personalized diabetes management for adults with type 1 diabetes.

To Use or Not to Use a Self-monitoring of Blood Glucose System? Real-world Flash Glucose Monitoring Patterns Using a Cluster Analysis of the FGM-Japan Study.

Objective This study investigated self-monitoring of blood glucose (SMBG) adherence and flash glucose monitoring patterns using a cluster analysis in Japanese type 1 diabetes (T1D) patients with intermittently scanned continuous glucose monitoring (isCGM). Methods We measured SMBG adherence and performed a data-driven cluster analysis using a hierarchical clustering in T1D patients from Japan using the FreeStyle Libre system. Clusters were based on three variables (testing glucose frequency and referred Libre data for hyperglycemia or hypoglycemia). Patients We enrolled 209 participants. Inclusion criteria were patients with T1D, duration of isCGM use ≥3 months, age ≥20 years old, and regular attendance at the collaborating center. Results The rate of good adherence to SMBG recommended by a doctor was 85.0%. We identified three clusters: cluster 1 (low SMBG test frequency but high reference to Libre data, 17.7%), cluster 2 (high SMBG test frequency but low reference to Libre data, 34.0%), and cluster 3 (high SMBG test frequency and high reference to Libra data, 48.3%). Compared with other clusters, individuals in cluster 1 were younger, those in cluster 2 had a shorter Libre duration, and individuals in cluster 3 had lower time-in-range, higher severe diabetic distress, and high intake of snacks and sweetened beverages. There were no marked differences in the incidence of diabetic complications and rate of wearing the Libre sensor among the clusters. Conclusion We stratified the patients into three subgroups with varied clinical characteristics and CGM metrics. This new substratification might help tailor diabetes management of patients with T1D using isCGM.

A Pragmatic Pilot Cluster-Randomized Study of Tobacco Screening and Smoking Cessation Program for Community Pharmacies in Japan: FINE Program.

OBJECTIVES: To investigate the effectiveness of a smoking cessation program (FINE program) in community pharmacies. METHODS: A cluster-randomized controlled trial was conducted in 11 community pharmacies in Japan. The participants were randomly assigned to a pharmacist-led structured smoking cessation program (intervention group) or pharmacist-led usual care (control group). The intervention group was followed up over the telephone on the third day of smoking cessation, and ongoing follow-up and advice were provided according to the original smoking cessation guidebook developed for the current study based on a behavioral change approach. The control group received brief advice and ready-made pamphlets on smoking cessation from pharmacists upon their visit to these community pharmacies. The primary outcome was continued smoking cessation as determined by self-reporting and carbon monoxide monitoring with a microsmokerlyzer after 3 months. RESULTS: Five hundred and seventy-two smokers who met the eligibility criteria visited the pharmacies included in the study. Of these individuals, 24 patients agreed to participate in the study. The quit rates were 45.5% and 18.2% in the intervention and control groups, respectively (P = 0.380, effect size = 0.60). CONCLUSION: Based on the effect size values, the FINE program may be effective to some extent, but the difference was not significant. We speculate that this is related to the small sample size due to difficulty in recruiting. Further studies with an effective recruitment method and larger sample sizes are needed to accurately verify the effectiveness of this program.

Diurnal variations of brown fat thermogenesis and fat oxidation in humans.

BACKGROUND/OBJECTIVES: Disturbed circadian rhythm is associated with an increased risk of obesity and metabolic disorders. Brown adipose tissue (BAT) is a site of nonshivering thermogenesis (NST) and plays a role in regulating whole-body energy expenditure (EE), substrate metabolism, and body fatness. In this study, we examined diurnal variations of NST in healthy humans by focusing on their relation to BAT activity. METHODS: Forty-four healthy men underwent 18F-fluoro-2-deoxy-D-glucose positron emission tomography and were divided into Low-BAT and High-BAT groups. In STUDY 1, EE, diet-induced thermogenesis (DIT), and fat oxidation (FO) were measured using a whole-room indirect calorimeter at 27 °C. In STUDY 2, EE, FO, and skin temperature in the region close to BAT depots (Tscv) and in the control region (Tc) were measured at 27 °C and after 90 min cold exposure at 19 °C in the morning and in the evening. RESULTS: In STUDY 1, DIT and FO after breakfast was higher in the High-BAT group than in the Low-BAT group (P < 0.05), whereas those after dinner were comparable in the two groups. FO in the High-BAT group was higher after breakfast than after dinner (P < 0.01). In STUDY 2, cold-induced increases in EE (CIT), FO, and Tscv relative to Tc in the morning were higher in the High-BAT group than in the Low-BAT group (P < 0.05), whereas those after dinner were comparable in the two groups. CIT in the High-BAT group tended to be higher in the morning than in the evening (P = 0.056). CONCLUSION: BAT-associated NST and FO were evident in the morning, but not in the evening, suggesting that the activity of human BAT is higher in the morning than in the evening, and thus may be involved in the association of an eating habit of breakfast skipping with obesity and related metabolic disorders.

Pharmacist-Delivered Smoking Cessation Program in Community Pharmacy (The FINE Program) in Japan-The Development of a Training Course and a Feasibility Study.

AIM: Although smoking cessation support has been recommended as a routine component of pharmacists'duties, there is limited evidence of smoking cessation being achieved successfully in community pharmacy. The aim of this study was to develop a new smoking cessation program for use in the community pharmacy setting and investigate its feasibility. METHODS: A feasibility study (the Family pharmacist's Intervention for Nicotine Elimination [FINE] program) was conducted using 8 pharmacists at 2 community pharmacies in Japan. The pharmacists recruited as subjects smokers 20 or more years of age who were taking medications such as antidiabetes drugs. The patients completed questionnaires assessing their smoking status, and the pharmacists provided them with smoking cessation support services. Participating patients met with the pharmacists or talked to them on the phone 5 times at 2- to 4-week intervals and received personalized and structured brief smoking cessation advice. The primary outcome was continuous abstinence determined by Micro Smokerlyzer carbon monoxide monitor at 3 months. RESULTS: Of 5306 patients, 2296 patients were screened and the rate of smoking was found to be 12.7%. Five smoking patients received the FINE program from pharmacists who had received training. One of the 5 succeeded in quitting smoking after 3 months. CONCLUSIONS: This is the first study to target Japanese smoking patients in community pharmacies with a brief structured intervention. The results tentatively support the feasibility of the FINE program. Further research including a randomized controlled trial is required to confirm the effectiveness of the FINE program.

An optimal condition for the evaluation of human brown adipose tissue by infrared thermography.

Brown adipose tissue (BAT) is responsible for non-shivering thermogenesis and is an attractive therapeutic target for combating obesity and related diseases. Human BAT activity has been evaluated by 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (18FDG-PET/CT) under acute cold exposure, but the method has some serious limitations, including radiation exposure. Infrared thermography (IRT) may be a simple and less-invasive alternative to evaluate BAT activity. In the present study, to establish an optimal condition for IRT, using a thermal imaging camera, skin temperature was measured in the supraclavicular region close to BAT depots (Tscv) and the control chest region (Tc) in 24 young healthy volunteers. Their BAT activity was assessed as the maximal standardized uptake value (SUVmax) by 18FDG-PET/CT. Under a warm condition at 24-27°C, no significant correlation was found between the IRT parameters (Tscv, Tc,, and the difference between Tscv and Tc,, Δtemp) and SUVmax, but 30-120 min after cold exposure at 19°C, Tscv and Δtemp were significantly correlated with SUVmax (r = 0.40-0.48 and r = 0.68-0.76). Δtemp after cold exposure was not affected by mean body temperature, body fatness, and skin blood flow. A lower correlation (r = 0.43) of Δtemp with SUVmax was also obtained when the participant's hands were immersed in water at 18°C for 5 min. Receiver operating characteristic analysis revealed that Δtemp after 30-60 min cold exposure can be used as an index for BAT evaluation with 74% sensitivity, 92% specificity, and 79% diagnostic accuracy. Thus, IRT may be useful as a simple and less-invasive method for evaluating BAT, particularly for large-scale screening and longitudinal repeat studies.

Dietary salt reduction in rural patients with albuminurea using family and community support: the Mima study.

BACKGROUND: Residents of rural communities are often more socially connected compared to urban dwellers. Using family and community support to motivate health behavior change may be useful in rural settings. The objective of this study was to pilot a salt reduction (SR) intervention for rural albuminuria patients using support from family and neighborhood residents compared to a usual care condition. The primary outcome was change in urine albumin-creatinine ratio (ACR). METHODS: All consecutive outpatients with an ACR >= 30 mg/gCr were recruited from the Koyadaira Clinic. Patients self-selected their participation in the intervention group (IG) or the control group (CG) because the rural population expressed concern about not being treated at the same time. In the IG, patients and their families were educated in SR for 30 minutes in their home by experienced dieticians. In addition, patients, families and neighborhood residents were also educated in SR for 2 hours at a public town meeting hall, with educational content encouraging reduction in salt intake through interactive activity. The CG received conventional treatment, and ACR and blood pressure (BP) were measured after 3 months. RESULTS: Of the 37 subjects recruited (20 male, 16 female, mean age; 72.8 +/- 9.2 years), 36 completed the 3-month follow up and were analyzed. In the IG, ACR decreased significantly from baseline (706 +/- 1,081 to 440 +/- 656; t = 2.28, p = 0.04) and was reduced compared to the CG (213 +/- 323 to 164 +/- 162; F = 3.50, p = 0.07), a treatment effect approaching significance. Systolic BP in the IG (145 +/- 14 to 131 +/- 13 mmHg; t = 3.83, p = 0.002) also decreased significantly compared to the CG (135 +/- 13 to 131 +/- 14; F = 4.40, p = 0.04). CONCLUSIONS: Simultaneous education of patients, their families and neighborhood residents may be important in rural areas for treatments and interventions requiring health behavior change. TRIAL REGISTRATION: UMIN000001972.

S447X polymorphism in the lipoprotein lipase gene and the adiponectin level in the general population: results from the Mima study.

AIM: Lipoprotein lipase (LPL) plays an important role in lipid metabolism. There is an association between the common S447X polymorphism in the LPL gene and high-density lipoprotein cholesterol (HDL-C) levels, and some association between circulating HDL-C and adiponectin levels has been suggested; however, it is not known whether there is any association between the S447X polymorphism and adiponectin levels. The aim of this study was to investigate whether the LPL S447X polymorphism was associated with adiponectin in the general population. METHODS: LPL S447X was analyzed in 277 community-dwelling subjects (123 men and 154 women, mean age; 65+/-13 years) in the Mima study. Whole samples were genotyped using a fluorescent allele-specific DNA primer assay system. The allele frequencies and any associations with serum lipid and adiponectin levels were investigated. RESULTS: The allele frequencies were S=0.875 and X=0.125 for the LPL S447X polymorphism. The carriers of the X allele had significantly higher levels of adiponectin and HDL-C than non-carriers. The presence of the X allele was significantly associated with higher adiponectin levels, independent of age, sex, body mass index, smoking and HDL-C in multiple regression analyses. CONCLUSION: The LPL S447X polymorphism might therefore be significantly associated with higher adiponectin levels, independent of HDL-C.

Oxidative stress, inflammation, and atherosclerotic changes in retinal arteries in the Japanese population; results from the Mima study.

Oxidative stress and inflammation are known to play roles in the pathogenesis of vascular events. The aim of this study was to investigate the relationship between oxidative stress, inflammation, and atherosclerosis in the general population. A population-based, cross-sectional study was made of 282 people (126 men and 156 women, mean age; 65 13, mean BMI; 25.4 2.7 kg/m (2) ) recruited from the Mima study in Tokushima Prefecture. Risk factors included age, sex, body mass index (BMI), cigarette smoking, systolic and diastolic pressure, fasting blood glucose, serum lipids, and high-sensitive C-reactive protein (hs-CRP). Oxidative stress in blood samples was measured by the diacron reactive oxygen metabolites (ROMs) test. The degree of sclerotic change was determined from fundus photographs according to Scheie's classification. After adjustment for age and sex, ROM levels positively correlated with hs-CRP levels, but not with ghrelin, leptin and adiponectin levels. Furthermore, ROM and hs-CRP levels positively and individually correlated with the grade of sclerotic change in the fundus oculi independent of age in a multiple regression analysis. These results suggest that oxidative stress and chronic inflammation promote atherosclerosis in the retinal arteries in the general population.

The common -55 C/T polymorphism in the promoter region of the uncoupling protein 3 gene reduces prevalence of obesity and elevates serum high-density lipoprotein cholesterol levels in the general Japanese population.

Uncoupling protein 3 (UCP3) is considered to be associated with obesity, given its function in the regulation of energy and lipid metabolism. An increased body mass index (BMI) and a decreased level of high-density lipoprotein cholesterol (HDL-C) are risk factors for cardiovascular disease. The purpose of this study was to investigate whether the UCP3 promoter -55 C/T single nucleotide polymorphism (UCP3 -55 C/T SNP) was associated with obesity according to the criteria for Japanese (BMI > or = 25 kg/m2), BMI, and serum HDL-C levels in the general Japanese population. The subjects, numbering 282 and aged 65 +/- 13 years (mean +/- SD), were recruited through an annual health checkup of residents of Mima city, Tokushima, in Japan. Body mass index, blood pressure, biochemical indexes including lipid, and lipoprotein profiles were measured. The UCP3 -55 C/T SNP was determined with a fluorescence-based allele-specific DNA primer assay system. The frequency of the -55 T allele was 30.0%. Subjects with the T/T genotype had significantly higher HDL-C levels than those with the C/C genotype or the C/T genotype. Furthermore, subjects with the T/T genotype had a significantly lower BMI than those with the C/C genotype. A multivariate analysis revealed that the -55 T allele was a significant independent variable contributing to the variance in HDL-C levels and BMI. The T/T genotype was associated with a lower prevalence of obesity than the C/C and C/T genotypes, with an odds ratio of 0.358 (95% confidence interval, 0.132-0.972; P = .037). In conclusion, the UCP3 -55 C/T SNP was associated with elevated HDL-C levels and a reduced BMI, independent of modifiable factors such as lifestyle. Furthermore, this polymorphism, when expressed in its homozygous form, reduced the prevalence of obesity in Japanese.

The UCP2-866 A/A genotype is associated with low density lipoprotein particle sizes in the general population.

BACKGROUND: It has been reported that a common G-->A single nucleotide polymorphism (SNP) at the position -866 of the uncoupling protein-2 promoter (UCP2-866 G/A SNP) modulates UCP2 expression in adipose tissue and pancreatic beta-cell function, and lipid profiles. Reduced low density lipoprotein (LDL) particle size is a significant predictor of the development for coronary artery disease. The purpose of this study was to investigate whether the UCP2-866 G/A SNP was associated with serum LDL particle characteristics in a general Japanese population. MATERIAL/METHODS: In 279 subjects (age 65+/-13 years), body mass index (BMI), percent body fat, blood pressure, and blood biochemical profiles were measured. The UCP2-866 G/A SNP was determined with a fluorescence-based allele-specific DNA primer assay system. LDL particle characteristics were analyzed by high-resolution polyacrylamide gel electrophoresis. RESULTS: The frequency of the -866 A allele was 47.8%. There was no difference in triglyceride, total cholesterol, LDL-cholesterol, HDL-cholesterol, and small dense LDL levels between genotypes. However, subjects with the -866 A/A genotype had significantly lower mean LDL particle size levels (263.5+/-4.9 angstroms) than those with the -866 G/G genotype (264.6+/-4.9 angstroms, P=0.034). Multiple regression analysis revealed that the -866 A/A genotype was a significant variable contributing to the variance in the reduced LDL particle size levels (P=0.012). CONCLUSIONS: The -866 A/A genotype may contribute to reduced LDL particle size levels, a significant risk factor for the development of coronary artery disease.

The Trp64Arg polymorphism of the beta3-adrenergic receptor gene is associated with increased small dense low-density lipoprotein in a rural Japanese population: the Mima study.

The presence of small dense low-density lipoprotein (sdLDL) is closely associated with an increased risk of developing coronary artery disease. The Trp64Arg polymorphism of the beta(3)-adrenergic receptor (beta(3)-AR) gene is a genetic marker for obesity-related traits. However, any possible association between this polymorphism and sdLDL profiles is unclear. The objective of this study is to investigate the effects of the polymorphism of the beta(3)-AR gene on LDL particle size and sdLDL in a rural Japanese population. Among 277 subjects, body mass index, blood pressure, fasting serum insulin levels, and insulin resistance index (fasting glucose x fasting insulin/405) were determined. The polymorphism of the beta(3)-AR gene was assessed by polymerase chain reaction-restriction fragment length polymorphism using buccal samples. Low-density lipoprotein particle size and sdLDL were measured with the electrophoretic separation of lipoproteins on the LipoPrint System (Quantimetrix, Redondo Beach, CA). The frequency of the beta(3)-AR allele was 0.19. In Arg carriers (Trp/Arg or Arg/Arg), the mean value of LDL particle size was smaller than that of non-Arg carriers (Trp/Trp) (P < .05). The area percentage of sdLDL was higher in Arg carriers (P < .05) than in non-Arg carriers. A multiple regression analysis showed that the area percentage of sdLDL was correlated with the polymorphism of the beta(3)-AR gene (P < .05), independently of age, sex, body mass index, smoking, and insulin resistance index. The present findings suggest that the beta(3)-AR gene polymorphism plays a role in the genetic predisposition to increased sdLDL, independently of insulin resistance.