Quality of Life in Japanese People with Type 2 Diabetes Switching from Multiple Daily Insulin Injections to Once-Daily iGlarLixi: SIMPLIFY Japan.

INTRODUCTION: Previous studies have shown that iGlarLixi, a fixed-ratio combination of insulin glargine 100 U/ml and lixisenatide, provides effective glycemic control in people with type 2 diabetes (T2D). The SIMPLIFY Japan study assessed the impact of switching from multiple daily insulin injections (MDI) to once-daily iGlarLixi on health-related quality of life (HRQOL) and glycemic parameters in Japanese people with moderately controlled T2D. METHODS: This 24-week, prospective, observational cohort study enrolled Japanese adults with T2D who switched from MDI therapy to iGlarLixi. Data were collected at baseline, 12, and 24 weeks; changes in Diabetes Therapy-Related Quality of Life (DTR-QOL) questionnaire score, glycated hemoglobin (HbA1c), body weight and self-reported treatment adherence were evaluated; the primary endpoint was change in DTR-QOL at 24 weeks. RESULTS: Sixty-six participants were enrolled and 61 were included in the full analysis set. Significant improvements were observed in total DTR-QOL score from baseline to week 24 (mean change + 10.8 points; P < 0.001), with higher scores observed in individual domains related to social/daily activities, treatment satisfaction, and reductions in treatment-related anxiety (P < 0.05). A small HbA1c increase was noted at week 24 (P < 0.001), while this did not appear to adversely affect HRQOL or treatment satisfaction. A significant reduction in body weight was observed at week 12 (mean change - 0.7 kg; P = 0.046). Self-reported treatment adherence increased from baseline to week 24, with the proportion of participants who never missed an insulin injection increasing from 55.7 to 77.6%. At week 24, the incidence of hypoglycemia and gastrointestinal adverse events was 18.2 and 27.3%, respectively. CONCLUSIONS: Switching from MDI to iGlarLixi therapy in Japanese people with T2D was associated with enhanced HRQOL (despite slight elevation in HbA1c) and improved treatment adherence, with a favorable safety profile. These findings support the beneficial role of iGlarLixi in the management of T2D in real-world Japanese clinical practice. STUDY REGISTRATION: Japan Registry of Clinical Trials (jRCT1041210151).

Impact of Participant Characteristics on Clinical Outcomes with iGlarLixi in Type 2 Diabetes: Post Hoc Analysis of SPARTA Japan.

INTRODUCTION: The real-world SPARTA Japan study confirmed the effectiveness and safety of the fixed-ratio combination of insulin glargine 100 U/mL plus lixisenatide (iGlarLixi) once daily over 6 months in Japanese people with type 2 diabetes (T2D). This post hoc analysis examined the impact of participant characteristics on the achievement of age-defined glycaemic targets with iGlarLixi therapy. METHODS: The retrospective, observational SPARTA Japan study included adults with T2D who initiated iGlarLixi. In this analysis, data from insulin-naïve and insulin-experienced participants were separately assessed to compare glycated haemoglobin (HbA1c), body weight and safety outcomes between those who achieved ('achieved' group) and those who did not achieve ('not-achieved' group) age-defined glycaemic targets after 6 months of iGlarLixi. The not-achieved group was further stratified by whether or not their iGlarLixi dose was increased during treatment. RESULTS: In total, 418 participants were included in this analysis (138 insulin naïve and 280 insulin experienced). Among both insulin-naïve and insulin-experienced participants, those in the achieved group were older and had lower baseline HbA1c than those in the not-achieved group. Compared with the not-achieved group, the achieved group showed significantly greater HbA1c reductions from baseline (in both insulin-naïve and insulin-experienced participants) and significantly greater body weight reductions (in insulin-naïve participants), despite some participants in the not-achieved group receiving significantly higher insulin glargine doses than those in the achieved group. In both insulin-naïve and insulin-experienced participants, the incidence of hypoglycaemia and gastrointestinal-related adverse events was similar in the achieved and not-achieved groups. In a multivariate analysis, glycaemic target achievement was significantly more likely in older individuals and those who lost weight during iGlarLixi treatment. CONCLUSIONS: Achievement of age-defined glycaemic targets with iGlarLixi treatment for 6 months was significantly affected by increased age and body weight loss, regardless of prior insulin exposure. TRIAL REGISTRATION: UMIN-CTR Trials Registry, UMIN000044126; registered 10 May 2021.

iGlarLixi is an injectable product used to treat type 2 diabetes that contains a fixed combination of two drugs, insulin glargine (at a concentration of 100 U/mL) and lixisenatide. The SPARTA Japan study investigated the effectiveness of controlling blood glucose levels and the safety of iGlarLixi in Japanese people when taken once daily for over 6 months as part of their routine medical care. The analysis reported in this article looked back at data from SPARTA Japan to assess whether certain characteristics of the people who took part in the study affected how well blood glucose targets were met. People who had previously taken insulin and those who had not were identified, and their results were assessed separately. The people were divided into those who had met their blood glucose level target (with the target defined as the glycated haemoglobin level for each person based on their age) and those who had not met their target. It was found that people who achieved their blood glucose target while receiving iGlarLixi were more likely to be older, to have had a lower glycated haemoglobin level before starting iGlarLixi, and to have lost weight during treatment than those who did not achieve their target, whether or not they had previously been treated with insulin. Side effects of excessively low blood glucose levels or gastrointestinal upset with iGlarLixi treatment occurred in a similar number of people who achieved or did not achieve their blood glucose target.

Use of iGlarLixi for the Management of Type 2 Diabetes in Japanese Clinical Practice: Prior Treatment Subgroup Analysis of the SPARTA Japan Study.

INTRODUCTION: iGlarLixi, a fixed-ratio combination of insulin glargine 100 U/mL and the glucagon-like peptide 1 receptor agonist (GLP-1 RA) lixisenatide, is one option for treatment intensification in individuals with type 2 diabetes (T2D) who are unable to achieve targeted glycaemic control with their current glucose-lowering agent. Real-world data on the impact of prior treatment on the effectiveness and safety of iGlarLixi may be useful to guide individualised treatment decisions. METHODS: This analysis of the 6-month, retrospective, observational SPARTA Japan study compared glycated haemoglobin (HbA1c), body weight and safety for pre-specified subgroups defined by prior treatment: post oral antidiabetic agent (OAD), GLP-1 RA, basal insulin (BI) + OADs (BOT), GLP-1 RA + BI or multiple daily injections (MDI). The post BOT and MDI subgroups were further divided on the basis of prior dipeptidyl peptidase 4 inhibitor (DPP-4i) use, and the post MDI group was divided on the basis of whether participants continued bolus insulin. RESULTS: Of the 432 participants in the full analysis set (FAS), 337 were included in this subgroup analysis. Across subgroups, mean baseline HbA1c ranged from 8.49% to 9.18%. iGlarLixi significantly (p < 0.05) reduced mean HbA1c from baseline in all but the post GLP-1 RA + BI group. At 6 months, these significant reductions ranged from 0.47% to 1.27%. Prior DPP-4i exposure had no impact on the HbA1c-lowering effect of iGlarLixi. Mean body weight decreased significantly in the FAS (0.5 kg) and the post BOT (1.2 kg) and MDI (1.5 and 1.9 kg) subgroups but increased in the post GLP-1 RA subgroup (1.3 kg). iGlarLixi treatment was generally well tolerated, with very few participants discontinuing because of hypoglycaemia or gastrointestinal events. CONCLUSION: In participants with suboptimal glycaemic control on various regimens, 6 months of iGlarLixi treatment improved HbA1c in all but one prior treatment subgroup (GLP-1 RA + BI), and was generally well tolerated. TRIAL REGISTRATION: UMIN-CTR Trials Registry, UMIN000044126; registered 10 May 2021.

Despite initially receiving oral treatment for their diabetes, many individuals with type 2 diabetes are unable to achieve their blood glucose targets and require treatment intensification as their disease progresses. In these individuals, options for treatment intensification include adding an injectable therapy, such as a glucagon-like peptide 1 receptor agonist or basal insulin, or the combination of both. However, the impact of previously received treatments on the ability of treatment intensification to improve outcomes in these individuals has yet to be evaluated. Here, we report the findings of an analysis that aimed to determine the influence of different treatment backgrounds on the effectiveness and safety of iGlarLixi, a fixed-ratio combination (i.e. combined as a single subcutaneous injection) of the glucagon-like peptide 1 receptor agonist lixisenatide and basal insulin glargine 100 U/mL, in Japanese individuals with type 2 diabetes. We found that iGlarLixi improved glycaemic control and was well tolerated in most individuals, regardless of previously received treatments. These results suggest that iGlarLixi may offer an effective option for improving outcomes in Japanese individuals with type 2 diabetes who require treatment intensification.

Use of iGlarLixi for Management of Type 2 Diabetes in Japanese Clinical Practice: SPARTA Japan, a Retrospective Observational Study.

INTRODUCTION: Many individuals with type 2 diabetes (T2D) experience suboptimal glycemic control. Treatment intensification options include fixed-ratio combination products containing a basal insulin and a glucagon-like peptide-1 receptor agonist, such as iGlarLixi (insulin glargine 100 U/mL and lixisenatide). This study aimed to provide real-world evidence of the effect of iGlarLixi in Japanese clinical practice. METHODS: SPARTA Japan was a non-comparative, observational study conducted at 27 institutions in Japan. Anonymized individual-level data from adults with T2D receiving iGlarLixi in routine clinical practice were retrospectively collected. The primary study objective was to assess the impact of iGlarLixi on the change in glycated hemoglobin (HbA1c) at 6 months' post-treatment initiation, with preplanned subanalyses to determine the influence of baseline characteristics. Secondary and exploratory endpoints included assessment of the proportion of individuals achieving HbA1c targets, change in body weight, and incidence and severity of hypoglycemia and gastrointestinal events. RESULTS: The full analysis set included 432 individuals, with data available at 6 months for 426. Of the 432 individuals, the mean (SD) age at baseline was 61.6 (12.8) years and the majority had a T2D duration of ≥ 10 years [mean (SD) 13.3 (10.4) years]. At 6 months, HbA1c had significantly decreased versus baseline ( -0.85%; P < 0.0001), with a greater decrease in those aged < 65 years, with a shorter duration of T2D and higher baseline HbA1c. A significant increase in the proportion of participants achieving age-specific HbA1c versus baseline was observed. Mean body weight decreased by 0.5 kg (P = 0.0034 versus baseline). There were few hypoglycemia and gastrointestinal events (in individuals with HbA1c data); no severe hypoglycemic events were reported. CONCLUSIONS: The results of this real-world study indicate that iGlarLixi may improve glycemic control without serious adverse events in Japanese individuals with T2D who have suboptimal glycemic control on current treatment regimens and switch to iGlarLixi. TRIAL REGISTRATION: UMIN-CTR Trials Registry, UMIN000044126; registered 10 May 2021.

The first medicines for treating diabetes that many individuals with type 2 diabetes receive are administered orally; however, for most individuals, these oral drugs are not enough to achieve blood glucose targets as their disease progresses. Treatment intensification options include adding an injectable therapy, such as a glucagon-like peptide-1 receptor agonist or basal insulin, or the combination of both, the use of which has been studied extensively and has been shown to be a simple and well-tolerated option. Here, we report the findings of a study that retrospectively evaluated the outcomes of 432 Japanese individuals who took iGlarLixi, which consists of the glucagon-like peptide-1 receptor agonist lixisenatide and basal insulin glargine 100 U/mL as a fixed-ratio combination (i.e., combined as a single subcutaneous injection), over 6 months of treatment. We found that iGlarLixi improved blood glucose levels in these individuals, and was associated with few hypoglycemia or gastrointestinal adverse events. These results suggest that iGlarLixi may offer an effective option for improving glycemic control in Japanese individuals with type 2 diabetes who require treatment intensification because their blood glucose goals have not been achieved with oral drugs alone or co-administered with a glucagon-like peptide-1 receptor agonist or basal insulin.

Use of digital artery perforator flaps for repairing soft tissue defects after fasciectomy for Dupuytren's contractures in the ring and little fingers: A case report.

Fasciectomy is the standard treatment for Dupuytren's contracture, but, in many cases, skin defects may occur after fasciectomy. If the preoperative contracture is severe, the skin defect is large, which makes covering the defect difficult. We describe a case of severe skin defects after fasciectomy of Dupuytren's contractures in the ring and little fingers covered with multiple digital artery perforator (DAP) flaps . A 58-year-old man with extension restrictions of the ring and little fingers on his left hand was diagnosed with Dupuytren's contracture. The angles of insufficient extension were 70° and 40° for the metacarpophalangeal and proximal interphalangeal joints, respectively, of the little finger and 42° for the metacarpophalangeal joint of the ring finger. DAP flaps were used to cover the defect on the ring finger's metacarpophalangeal joint and little finger's proximal interphalangeal joint, whereas an ulnar palmar DAP flap was used on the defect on the little finger's metacarpophalangeal joint. The flaps survived without any complications, and, at 6 months postoperatively, satisfactory results were obtained. The extension angles were 0° for the metacarpophalangeal and proximal interphalangeal joints of the little finger and -5° for the ring finger's metacarpophalangeal joint. Such flaps can be designed to fit the width of the skin defect and can be applied to a large skin defect by combining the perforator flaps. Thus, the use of DAP flaps after fasciectomy to cover defects is considered helpful, even in cases of Dupuytren's contracture with severe extension restriction.

Ulnar Artery Perforator Adiposal Flap for Paraffinoma Treatment in a Patient With Leprosy: A Case Report.

Leprosy is a chronic infection in humans that mainly affects the peripheral nerves and skin. Paraffin filling has been previously used for muscle atrophy treatment. However, the formation of paraffin granulomas (paraffinomas) can occur over the long term. We encountered a patient with leprosy who had hypothenar muscle atrophy caused by ulnar neuropathy. The patient was treated with paraffin injection at the hypothenar site for cosmetic appearance 60 years ago. Consequently, the paraffin formed a paraffinoma and a recurrent infected skin ulcer. Thus, paraffinoma removal and transfer of ulnar artery perforator adiposal flap (140 × 20 mm) were performed. The ulnar artery perforator adiposal flap was used for infection control and filling the dead space after paraffin removal. The skin healed without complications. Ultrasound confirmed residual adipose tissue and blood flow at the last follow-up.

A Real-World, Observational Study of the Initiation, Use, and Effectiveness of Basal-Bolus or Premixed Insulin in Japanese People with Type 2 Diabetes.

INTRODUCTION: Basal-bolus (BB) and premixed insulin regimens may lower fasting plasma glucose (FPG) and postprandial plasma glucose (PPG), but are complex to use and associated with weight gain and hypoglycaemia. Although randomized controlled trials and prospective observational studies in insulin-naïve Japanese patients with type 2 diabetes (T2D) inadequately controlled with oral antidiabetic drugs (OADs) initiating these regimens have been conducted, real-world data are lacking. This study describes the characteristics of patients initiating these regimens in routine clinical practice and identifies the course and outcomes of therapy in the year following initiation. METHODS: Adults with T2D initiating BB or premixed regimens following OAD therapies held in a Japanese electronic medical record database were identified (2010-2019). Subcohorts were determined by treatment changes during ≤ 12 months of follow-up (no change, intensified, switched, discontinued). Outcomes included change in glycated haemoglobin levels (HbA1c), probability of first reaching HbA1c < 7% (stratified by baseline OAD number, HbA1c and age), and hypoglycaemia incidence. RESULTS: The main cohorts comprised 1315 BB and 1195 premixed therapy initiators. Most individuals (67.9%) initiated BB as inpatients; 50.8% switched at a mean of 47.6 days. Mean HbA1c lowering was - 2.5% for BB and - 1.4% for premixed regimens (no change cohorts). Overall, a greater proportion achieved HbA1c < 7% if they were (at baseline) taking fewer OADs, in a lower HbA1c category, and aged ≥ 65 years. Hypoglycaemia incidence (< 70 mg/dl) was higher with BB than premixed regimens and lower in patients aged < 65 years. CONCLUSION: Greater HbA1c reductions, but a higher incidence of hypoglycaemia, were reported with BB versus premixed regimens, while both cohorts demonstrated clinically meaningful reductions in HbA1c during follow-up. After initiation, most premixed regimens remained unchanged, whereas switches from BB to less intensive regimens were numerous, in accordance with the use of BB for a limited duration to improve FPG and PPG control.

Digital artery perforator flap transfer for volar soft tissue defect due to dissociation from joint contracture in camptodactyly.

Camptodactyly is a condition defined by persistent flexion contracture of the proximal interphalangeal joints of the hand. Surgical treatment requires flaps for the dissection of the skin and the resulting soft tissue defect, soft tissue release, and sometimes reconstruction of the extension mechanism. Z-plasty and transposition flap have been reported as methods used in soft tissue defects. In this case, covering the defects of the digits was necessary for keeping the wound clean; thus, we should select a surgical method that facilitates stable and reliable blood flow of the flap. The digital artery perforator flap is pedicled and its transfer does not require the dissection of neurovascular bundles; therefore, it can be used safety and relatively easily. We considered the digital artery perforator flap to be a useful technique in terms of securing stable and reliable blood flow and not twisting the skin. Thus, we performed a digital artery perforator flap transfer for a volar soft tissue defect due to dissociation from proximal interphalangeal joint contracture in camptodactyly.

A Real-World Observational Study Evaluating the Probability of Glycemic Control with Basal Insulin or Glucagon-Like Peptide-1 Receptor Agonist in Japanese Patients with Type 2 Diabetes.

INTRODUCTION: The effectiveness of basal insulin (BI) or glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in providing glycemic control in patients with type 2 diabetes (T2D) in Japanese routine practice is not well known. This real-world observational study evaluated the probability of achieving glycemic control in Japanese patients with T2D uncontrolled by oral antidiabetic drugs (OADs) who initiated BI or GLP-1 RA therapy. METHODS: Patients with T2D aged ≥ 18 years initiating BI or GLP-1 RA therapy following treatment with OADs were selected from real-world data (RWD) retrieved from a large electronic medical record database in Japan, using data from 01 January 2010 to 30 June 2019. Patients were required to have glycated hemoglobin (HbA1c) ≥ 7% within 90 days prior to the first prescription of BI or GLP-1 RA. The probability of reaching first HbA1c < 7% was assessed over a 24-month period in cohorts of patients who initiated BI (n = 3477) or GLP-1 RA (n = 780) and in subcohorts by number of OADs at baseline (1, 2, or ≥ 3), HbA1c at baseline (≥ 7 to < 8%, ≥ 8 to < 9%, or ≥ 9%), and age (< 65 or ≥ 65 years). RESULTS: Mean (standard deviation) baseline HbA1c was 9.4% (1.8%) and 8.8% (1.4%) in patients initiating BI or GLP-1 RA therapy, respectively. The cumulative probability of achieving glycemic control was 50.1% with BI and 60.3% with GLP-1 RA therapy, respectively, at 12 months, and 60.8% and 66.6%, respectively, at 24 months. Quarterly (3-month intervals) conditional probabilities of achieving glycemic control decreased over time and were < 10% after 12 months. Patients with more OADs or higher HbA1c at baseline had a lower probability of achieving glycemic control. CONCLUSION: Among Japanese patients with T2D who initiated BI or GLP-1 RA therapy after treatment with OADs, the probability of reaching first glycemic control diminished over time. Further therapy intensification is warranted in patients who do not achieve glycemic control within 6-12 months with BI or GLP-1 RA, particularly those with high HbA1c or taking multiple OADs.

Patients with type 2 diabetes (T2D) who are taking oral antidiabetic drugs (OADs) but still have high blood glucose often require injectable drugs, such as basal insulin (BI) or glucagon-like peptide-1 receptor agonists (GLP-1 RAs). While BI and GLP-1 RAs have been shown to be effective in controlled clinical trials, it is unclear how well they improve blood glucose in real-world routine practice. Here, we report the results of an observational study that used data retrieved from a large electronic medical records database in Japan to explore how well BI and GLP-1 RAs allow patients to achieve glycemic control [glycated hemoglobin (HbA1c) < 7%].In Japanese patients with T2D receiving treatment with OADs and initiating BI or GLP-1 RA therapy, the probability of achieving glycemic control in the first quarter (3 months) after initiation was 20.3% with BI and 38.6% with GLP-1 RA. Among those patients who had not previously reached glycemic control, the probability of achieving first glycemic control declined over time, as evidenced in each quarterly assessment, and it was < 10% after the first year. Patients who had higher HbA1c levels or were taking multiple OADs were less likely to achieve glycemic control compared with those with lower HbA1c or taking fewer OADs. Our findings suggest that patients who have not achieved their glycemic goals within the first 6­12 months after starting BI or GLP-1 RA therapy have a low likelihood of achieving their target by maintaining the same therapy. For such patients, intensification with additional medication (e.g., combined BI and GLP-1 RA therapy) should be considered early in treatment.

Volar Locking Plate Fixation for Distal Radius Fractures by Intraoperative Computed Tomographic-Guided Navigation.

Purpose: Unstable distal radius intra-articular fractures require restoration of alignment. Exact fixation of intra-articular fragments is ideal. Here, we employed intraoperative computed tomography (CT) navigation to insert screws accurately in the intra-articular dorsal fragments during treatment with a volar locking plate for distal radius intra-articular fractures. The main purposes of this study were to evaluate the accuracy of this procedure and the postoperative stability of the articular fragments through CT findings, as well as to assess clinical outcomes. Methods: This study included 26 patients with distal radius fractures, who were treated with a volar locking plate using intraoperative CT navigation with a minimum follow-up of 12 months. Mean patient age was 63 years and mean follow-up was 16 months. We examined the position of the inserted distal screws and articular displacement on preoperative, intraoperative, and post-bone union CT images. The 3 distal ulnar screw positions that influence the stability of the dorsoulnar articular fragment were evaluated. The Mayo wrist score and Disabilities of the Arm, Shoulder, and Hand score were also clinically evaluated. Results: Computed tomography evaluation revealed that the distal locking screws were appropriately inserted at the subchondral position, with sufficient length to stabilize the dorsal fragments, and reduction and stability of the articular fragment were acceptable. At the final follow-up, mean Mayo wrist score was 90.8 and mean Disabilities of the Arm, Shoulder, and Hand score was 9.6. Conclusions: Intraoperative CT navigation was successfully used for volar locking plate fixation of intra-articular distal radius fractures. Computed tomography evaluation revealed that the screws were precisely inserted for articular fragments and bone union was achieved, maintaining good intra-articular alignment. The findings demonstrate the accuracy of volar locking plate fixation assisted by intraoperative CT navigation and the good clinical outcomes of this procedure. Type of study/level of evidence: Therapeutic IV.

Self-reported dietary flavonoid intake and serum markers of inflammation: the multiethnic cohort.

PURPOSE: To examine if dietary intake of foods rich in flavonoids, which have been shown to be inversely associated with chronic diseases, is associated with inflammatory processes. METHODS: This analysis includes controls of case-control studies nested within the Multiethnic Cohort (MEC) who completed a validated food frequency questionnaire at cohort entry. Biomarkers were assessed in blood donated during follow-up (mean = 9.6 years). We used multivariate linear regression adjusted for potential confounders to estimate associations between intake of flavanones, flavonols, and isoflavones and levels of adiponectin, leptin, C-reactive protein, interleukin (IL)-1ß, IL-6, IL-10, and tumor necrosis factor-α. RESULTS: Among the 1,287 participants, the respective median intakes of flavanones, flavonols, and isoflavones were 26.5, 12.4, and 1.3 mg/day at cohort entry. With the exception of flavanone intake, which was statistically significantly inversely associated with adiponectin (p = 0.01) and IL-6 concentrations (p = 0.01), none of the examined flavonoids was related with levels of adipokines or inflammatory markers. Heterogeneity by ethnicity was only observed for flavonol intake and IL-10 (pinteraction = 0.04) and may be the result of multiple testing. These null findings were confirmed in a subset of participants who completed a second dietary history within 2.6 years of blood draw. CONCLUSION: The current results do not support a consistent association between dietary intake of flavonoids and markers of inflammatory processes.

Dietary Red and Processed Meat Intake and Markers of Adiposity and Inflammation: The Multiethnic Cohort Study.

OBJECTIVE: The potential influence of dietary factors on inflammation is important for cancer prevention. Utilizing data from control participants (312 men, 911 women) in 2 nested case-control studies of cancer within the Multiethnic Cohort, we examined the associations of red and processed meat intake with serum levels of leptin, adiponectin, C-reactive protein (CRP), tumor necrosis factor (TNF)-α, and interleukin (IL)-6 and the mediator effect of body mass index (BMI) on the above associations (if present). METHODS: Multivariable linear models were applied to assess the association between red and processed meat intake at cohort entry and serum biomarker levels measured 9.1 years later after adjusting for covariates and to determine the mediator effect of BMI. RESULTS: Overall red and processed meat intake was positively associated with serum leptin levels in men (ß = 0.180, p = 0.0004) and women (ß = 0.167, p < 0.0001). In women, higher red and processed meat consumption was significantly associated with higher CRP (ß = 0.069, p = 0.03) and lower adiponectin levels (ß = -0.082, p = 0.005). In mediation analyses with red and processed meat intake and BMI as predictors, the associations of red and processed meat with biomarkers decreased substantially (as indicated by percentage change in effect: leptin in men, 13.4%; leptin in women, 13.7%; adiponectin in women, -4.7%; CRP in women, 7.4%) and were no longer significant (p > 0.05), whereas BMI remained significantly associated with serum leptin (men: ß = 3.209, p < 0.0001; women: ß = 2.891, p < 0.0001), adiponectin (women: ß = -1.085, p < 0.0001), and CRP (women: ß = 1.581, p < 0.0001). CONCLUSION: The current data suggest that the amount of excess body weight or the degree of adiposity may mediate the relations between dietary red and processed meat intake and serum biomarkers associated with obesity and inflammation.

Soy Food Intake and Biomarkers of Breast Cancer Risk: Possible Difference in Asian Women?

Soy foods may protect against breast cancer in Asian but not in Western populations. We examined if the levels of various markers of breast cancer risk and inflammation, as well as the effects of soy food consumption on these markers, differ between Asian and non-Asian premenopausal women in two soy intervention trials. One study randomized 220 women to a 2-yr intervention and the other one randomized 96 women in a crossover design to examine the effects of consumption of 2 daily soy servings on nipple aspirate fluid (NAF) volume; estrogens in serum, NAF, and urine; insulin-like growth factor-1 (IGF-1), IGF-binding protein 3, and inflammatory markers in serum; and mammographic densities. Mixed linear models were applied to assess ethnic differences in biomarkers and response to the soy diet. Serum C-reactive protein, serum leptin, NAF volume, and NAF estrone sulfate were lower, while urinary isoflavones were higher in Asian than in non-Asian women. A significant interaction (pinteraction = 0.05) between ethnicity and soy diet was observed for IGF-1 but not for other biomarkers. The current findings suggest possible ethnic differences in levels of biomarkers for breast cancer risk but little evidence that Asian women respond differently to soy foods than non-Asian women.

Bioimpedence to Assess Breast Density as a Risk Factor for Breast Cancer in Adult Women and Adolescent Girls.

Although high mammographic density is one of the strongest predictors of breast cancer risk, X-ray based mammography cannot be performed before the recommended screening age, especially not in adolescents and young women. Therefore, new techniques for breast density measurement are of interest. In this pilot study in Guam and Hawaii, we evaluated a radiation-free, bioimpedance device called Electrical Breast DensitometerTM (EBD; senoSENSE Medical Systems, Inc., Ontario, Canada) for measuring breast density in 95 women aged 31-82 years and 41 girls aged 8-18 years. Percent density (PD) was estimated in the women's most recent mammogram using a computer-assisted method. Correlation coefficients and linear regression were applied for statistical analysis. In adult women, mean EBD and PD values of the left and right breasts were 230±52 and 226±50 Ω and 23.7±15.1 and 24.2±15.2%, respectively. The EBD measurements were inversely correlated with PD (rSpearman=-0.52, p<0.0001); the correlation was stronger in Caucasians (rSpearman=-0.70, p<0.0001) than Asians (rSpearman=-0.54, p<0.01) and Native Hawaiian/Chamorro/Pacific Islanders (rSpearman=-0.34, p=0.06). Using 4 categories of PD (<10, 10-25, 26-50, 51-75%), the respective mean EBD values were 256±32, 249±41, 202±46, and 178±43 Ω (p<0.0001). In girls, the mean EBD values in the left and right breast were 148±40 and 155±54 Ω; EBD values decreased from Tanner stages 1 to 4 (204±14, 154±79, 136±43, and 119±16 Ω for stages 1-4, respectively) but were higher at Tanner stage 5 (165±30 Ω). With further development, this bioimpedance method may allow for investigations of breast development among adolescent, as well as assessment of breast cancer risk early in life and in populations without access to mammography.

Adherence to cancer prevention recommendations and antioxidant and inflammatory status in premenopausal women.

For cancer prevention, the World Cancer Research Fund and American Institute for Cancer Research (WCRF/AICR) emphasise recommendations to improve individual behaviour, including avoidance of tobacco products, maintaining a lean body mass, participating in physical activity, consuming a plant-based diet, and minimising the consumption of energy-dense foods, such as sodas, red and processed meats and alcohol. In the present study of 275 healthy premenopausal women, we explored the association of adherence scores with levels of three biomarkers of antioxidant and inflammation status: serum C-reactive protein (CRP), serum γ-tocopherol and urinary F2-isoprostane. The statistical analysis applied linear regression across categories of adherence to WCRF/AICR recommendations. Overall, seventy-two women were classified as low ( ≤ 4), 150 as moderate (5-6), and fifty-three as high adherers ( ≥ 7). The unadjusted means for CRP were 2.7, 2.0 and 1.7 mg/l for low, moderate and high adherers (P trend= 0.03); this association was strengthened after adjustment for confounders (P trend= 0.006). The respective values for serum γ-tocopherol were 1.97, 1.63 and 1.45 µg/ml (P trend= 0.02 before and P trend= 0.03 after adjustment). Only for urinary F2-isoprostane, the lower values in high adherers (16.0, 14.5, and 13.3 ng/ml) did not reach statistical significance (P trend= 0.18). In an analysis by BMI, overweight and obese women had higher biomarker levels than normal weight women; the trend was significant for CRP (P trend< 0.001) and γ-tocopherol (P trend= 0.003) but not for F2-isoprostane (P trend= 0.14). These findings suggest that both adherence to the WCRF/AICR guidelines and normal BMI status are associated with lower levels of biomarkers that indicate oxidative stress and inflammation.

Association of estrogen measurements in serum and urine of premenopausal women.

AIMS: We evaluated conjugated and unconjugated urinary estrogen metabolites as surrogate biomarkers for serum levels of unconjugated E1 and E2 in premenopausal women. MATERIALS & METHODS: Repeated blood and urine samples were analyzed for estrogens and their metabolites using radioimmunoassays and liquid chromatography/mass spectrometry. RESULTS: The strongest correlation (r = 0.39) was observed between serum E1 and urinary E1 and E2. The correlations of urinary E2 (r = 0.35), E1 (r = 0.29), all E2 metabolites (r = 0.30), all E1 metabolites (r = 0.23) and total estrogens (r = 0.26) with serum E2 were only moderate although statistically significant. All correlations were substantially stronger for Whites than Asians. CONCLUSION: Urinary E2 emerged as the best predictor for serum E1 and E2, but the large intra-subject variability in urinary estrogen levels limits its use as a biomarker.

Disparity in diabetes risk across Native Hawaiians and different Asian groups: the multiethnic cohort.

We evaluated the impact of body mass index (BMI) and lifestyle risk factors on ethnic disparity in diabetes incidence among 89 198 Asian, Native Hawaiian, and white participants of the Multiethnic Cohort who completed multiple questionnaires. After 12 years of follow-up, 11 218 new cases were identified through self-report and health plan linkages. BMI was lowest in Chinese/Koreans, Japanese, and Filipinos (22.4, 23.5, and 23.9 kg/m(2)). Using Cox regression, the unadjusted hazard ratios were 1.9 (Chinese/Korean), 2.1 (Japanese, Mixed-Asian), 2.2 (Filipino), 2.5 (Native Hawaiian), and 2.6 (part-Asian) as compared with whites. With BMI added, the risk for Japanese, Filipinos, Chinese/Koreans, and mixed-Asians increased (8%-42%) but declined in part-Asians and Native Hawaiians (17%-31%). When lifestyle and dietary factors were also included, the risk was attenuated in all groups (6%-14%). Despite their lower BMI, Asian Americans have a higher diabetes risk than whites, but dietary and lifestyle factors do not account for the excess risk.

Various adiposity measures show similar positive associations with type 2 diabetes in Caucasians, native Hawaiians, and Japanese Americans: the multiethnic cohort.

The authors evaluated the association of body mass index (BMI), waist circumference (WC) and hip circumference (HC), waist-to-hip ratio (WHR), and waist-to-height ratio (WHtR) with diabetes in Caucasians, Native Hawaiians, and Japanese Americans aged 45 to 75 years in the Multiethnic Cohort. Diabetes cases were obtained from self-reports and by linkages with health insurance plans. The authors estimated adjusted prevalence odds ratios (PORs) and compared the area under the receiver operating characteristic curves (AUC). All measures were positively associated with diabetes prevalence; the PORs were 1.25 to 1.64 in men and 1.52 to 1.83 in women. In all 3 ethnic groups, the AUCs in men were greater for BMI than for the other measures, whereas in women, the AUCs were greater for combined models than for BMI alone, but the differences were small and not clinically significant. It does not appear that one anthropometric measure best reflects diabetes prevalence or performs better in one ethnic group than in another.

A priori-defined diet quality indexes and risk of type 2 diabetes: the Multiethnic Cohort.

AIMS/HYPOTHESIS: Dietary patterns have been associated with the incidence of type 2 diabetes, but little is known about the impact of ethnicity on this relationship. This study evaluated the association between four a priori dietary quality indexes and risk of type 2 diabetes among white individuals, Japanese-Americans and Native Hawaiians in the Hawaii component of the Multiethnic Cohort. METHODS: After excluding participants with prevalent diabetes and missing values, the analysis included 89,185 participants (11,217 cases of type 2 diabetes). Dietary intake was assessed at baseline with a quantitative food frequency questionnaire designed for use in the relevant ethnic populations. Sex- and ethnicity-specific HRs were calculated for the Healthy Eating Index-2010 (HEI-2010), the Alternative HEI-2010 (AHEI-2010), the Alternate Mediterranean Diet Score (aMED) and the Dietary Approaches to Stop Hypertension (DASH). RESULTS: We observed significant inverse associations between higher DASH index scores and risk of type 2 diabetes in white men and women, as well as in Japanese-American women and Native Hawaiian men, with respective risk reductions of 37%, 31%, 19% and 21% (in the highest compared with the lowest index category). A higher adherence to the AHEI-2010 and aMED diet was related to a 13-28% lower risk of type 2 diabetes in white participants but not in other ethnic groups. No significant associations with risk of type 2 diabetes were observed for the HEI-2010 index. CONCLUSIONS/INTERPRETATION: The small ethnic differences in risk of type 2 diabetes associated with scores of a priori-defined dietary patterns may be due to a different consumption pattern of food components and the fact that the original indexes were not based on diets typical for Asians and Pacific Islanders.