Associations of Plasma 25-Hydroxy Vitamin D and Dietary Vitamin D Intake with Insulin Resistance in Healthy Japanese Women.

We investigated the associations of plasma 25-hydroxy vitamin D (25(OH)D) concentration and the dietary intake of vitamin D with insulin resistance in Japanese women. Study participants were 406 Japanese women attended a health examination. They were not taking hormones or medications for diabetes and had no history of cancer, ischemic heart disease, or stroke. Information regarding medical history and lifestyle factors was obtained by a self-administered questionnaire, while hours of sun exposure were determined through interviews. Dietary intake of vitamin D was evaluated using a validated food frequency questionnaire. Fasting plasma glucose and insulin concentrations were measured, and insulin resistance (HOMA-IR) scores were calculated based on homeostasis model assessment. Women with vitamin D deficiency (25(OH)D<20 ng/mL) had significantly higher fasting plasma insulin concentration and HOMA-IR than did the other women. Plasma 25(OH)D concentration was significantly and inversely associated with fasting plasma insulin level and HOMA-IR after controlling for age, season, menopausal status, BMI, smoking status, alcohol intake, physical exercise, and intakes of fat and calcium. Dietary vitamin D intake was not associated with HOMA-IR concentration after adjusting for these covariates and hours of sun exposure. Although significant inverse association between plasma 25(OH)D concentration and HOMA-IR was observed in women with a low BMI, low fat intake, or a high calcium intake, the interaction terms were not statistically significant. Data suggest that plasma vitamin D, but not dietary vitamin D, is inversely associated with fasting plasma insulin concentration and HOMA-IR in non-diabetic Japanese women.

Cefcapene pivoxil-induced hypocarnitinemic hypoglycemia in elderly man with subclinical ACTH deficiency: a case report.

BACKGROUND: Drug-induced hypocarnitinemia has been noted as a cause of hypoglycemia in children. However, adult cases are extremely rare and pre-existing conditions (including endocrine disorders and frailty) have been suggested to be involved. Hypoglycemia due to drug-induced hypocarnitinemia is quite rare, and there were few reports of pivoxil-containing cephalosporin (PCC)-induced hypocarnitinemia in adults. CASE PRESENTATION: We present a case of an 87-year-old man with malnutrition, and frailty. He developed severe hypoglycemia with unconsciousness after taking cefcapene pivoxil hydrochloride, one of PCC, and hypocarnitinemia was diagnosed. Despite levocarnitine administration, asymptomatic mild hypoglycemia had persisted. Subsequent investigation revealed subclinical ACTH deficiency due to empty sella, which played a key role to maintain mild hypoglycemia as underlying disorder, and PCC-induced hypocarnitinemia triggered severe hypoglycemia. The patient responded to hydrocortisone therapy. CONCLUSIONS: We need to be aware of the facts that PCC can induce severe hypocarnitinemic hypoglycemia in elderly adults associated with frailty, malnutrition, and subclinical ACTH syndrome.

Sleep-related factors and circulating levels of sex hormones in premenopausal Japanese women.

Sleep disruption and circadian disruption have been proposed to be risk factors of breast cancer. The present study examined the associations of sleep-related factors, referring to night shift work, sleep habits, and sleep disturbances, with the plasma levels of sex hormones in premenopausal Japanese women. Study participants were 432 women who had regular menstrual cycles less than 40 days long. Information on their history of night shift work and sleep disturbances was obtained using a self-administered questionnaire. Information on their sleep habits, such as usual wake-up times, bedtimes, and ambient light level while sleeping, was obtained in an interview. The participants' height and weight were measured. Plasma concentrations of estradiol, testosterone, dehydroepiandrosterone sulfate, sex hormone-binding globulin (SHBG), FSH, and LH were also measured. After controlling for the phase of the menstrual cycle and other covariates, more years of night shift work ≥ once a week during the past 10 years was significantly associated with a lower SHBG and a higher free estradiol level. Shorter sleep duration was significantly associated with the higher total, bioavailable, and free testosterone levels. Sleep disturbance by awaking after sleep onset was significantly associated with a high free estradiol level. The data suggest that long-term night shift work, short sleep duration, and arousal during sleep are associated with higher estradiol or testosterone levels in premenopausal women.

Adult-onset reversible idiopathic hypogonadotropic hypogonadism in male adult carrying a WDR11 missense mutation.

Idiopathic hypogonadotropic hypogonadism (IHH) occurs mostly in childhood or adolescence and very rarely in adulthood. It is characterised by delayed onset of secondary sexual characteristics. Many genetic abnormalities have been reported in congenital IHH cases, but rarely in adult-onset IHH cases. IHH requires lifelong hormone replacement therapy; however, a few reports suggest the reversibility of this condition.In this case, after having his first child, a man in his 20s was diagnosed with gynecomastia followed by IHH. He improved with gonadotropin-releasing hormone replacement therapy and had two more children. The treatment was discontinued after 4 years, but the improvement was sustained. He had a heterozygous missense variant in WDR11 (c.2390G>A; p.Arg797His), which may play a role in adult-onset IHH reversal. Accumulation of such cases can contribute to our understanding of the pathogenesis and genetic component of IHH.

Comparison of Interstitial Fluid Glucose Levels Obtained by Continuous Glucose Monitoring and Flash Glucose Monitoring in Patients With Type 2 Diabetes Mellitus Undergoing Hemodialysis.

BACKGROUND: The accuracy of flash glucose monitoring (FGM, FreeStyle Libre Pro [FSL-Pro]) remains unclear in patients with type 2 diabetes mellitus (T2DM) undergoing hemodialysis. METHODS: We assessed 13 patients with T2DM undergoing hemodialysis. They simultaneously underwent FGM, continuous glucose monitoring (CGM, iPro2), and self-monitoring blood glucose (SMBG). RESULTS: Parkes error grid analysis against SMBG showed that 49.0% and 51.0% of interstitial fluid glucose (ISFG) levels measured using FGM and 93.3% and 6.7% of those measured using CGM fell into zones A and B, respectively. Mean absolute relative difference (MARD) against SMBG for FGM was significantly higher than that for CGM (19.5% ± 13.2% vs 8.1% ± 7.6%, P < .0001). Parkes error grid analysis of 2496 paired ISFG levels between FGM and CGM showed that 53.6%, 46.2%, and 0.2% of the plots fell into zones A, B, and C, respectively. Mean ISFG levels were lower with FGM than with CGM (143.7 ± 67.2 mg/dL vs 164.6 ± 58.5 mg/dL; P < .0001). Mean absolute relative difference of ISFG levels between FGM and CGM was 19.2% ± 13.8%. Among three groups classified according to CGM ISFG levels (hypoglycemia, <70 mg/dL; euglycemia, 70-180 mg/dL; and hyperglycemia, >180 mg/dL), the MARDs for hypoglycemia (31.9% ± 25.0%) and euglycemia (22.8% ± 14.6%) were significantly higher than MARD for hyperglycemia (13.0% ± 8.5%) (P < .0001 in both). CONCLUSIONS: Flash glucose monitoring may be clinically acceptable. Average ISFG levels were lower with FGM than with CGM, and MARDs were higher for hypoglycemia and euglycemia in patients with T2DM undergoing hemodialysis.

Combined Predictive Value of Extracellular Fluid/Intracellular Fluid Ratio and the Geriatric Nutritional Risk Index for Mortality in Patients Undergoing Hemodialysis.

The ratio of extracellular fluid (ECF) to intracellular fluid (ICF) may be associated with mortality in patients undergoing hemodialysis, possibly associated with protein-energy wasting. We therefore investigated the relationship of the ECF/ICF ratio and the geriatric nutritional risk index (GNRI) with the all-cause and cardiovascular-specific mortality in 234 patients undergoing hemodialysis. Bioimpedance analysis of the ECF and ICF was performed and the ECF/ICF ratio was independently associated with GNRI (ß = -0.247, p < 0.0001). During a median follow-up of 2.8 years, 72 patients died, of which 29 were cardiovascular. All-cause mortality was independently associated with a lower GNRI (adjusted hazard ratio [aHR] 3.48, 95% confidence interval [CI] 2.01-6.25) and a higher ECF/ICF ratio (aHR 11.38, 95%CI 5.29-27.89). Next, we divided patients into four groups: group 1 (G1), higher GNRI and lower ECF/ICF ratio; G2, lower GNRI and lower ECF/ICF ratio; G3, higher GNRI and higher ECF/ICF ratio; and G4, lower GNRI and higher ECF/ICF ratio. Analysis of these groups revealed 10-year survival rates of 91.2%, 67.2%, 0%, and 0% in G1, G2, G3, and G4, respectively. The aHR for G4 versus G1 was 43.4 (95%CI 12.2-279.8). Adding the GNRI alone, the ECF/ICF ratio alone, or both to the established risk model improved the net reclassification improvement by 0.444, 0.793 and 0.920, respectively. Similar results were obtained for cardiovascular mortality. In conclusion, the ECF/ICF ratio was independently associated with GNRI and could predict mortality in patients undergoing hemodialysis. Combining the GNRI and ECF/ICF ratio could improve mortality predictions.

The associations of fat tissue and muscle mass indices with all-cause mortality in patients undergoing hemodialysis.

Protein-energy wasting, which involves loss of fat and muscle mass, is prevalent and is associated with mortality in hemodialysis (HD) patients. We investigated the associations of fat tissue and muscle mass indices with all-cause mortality in HD patients. The study included 162 patients undergoing HD. The fat tissue index (FTI) and skeletal muscle mass index (SMI), which represent respective tissue masses normalized to height squared, were measured by bioimpedance analysis after dialysis. Patients were divided into the following four groups according to the medians of FTI and SMI values: group 1 (G1), lower FTI and lower SMI; G2, higher FTI and lower SMI; G3, lower FTI and higher SMI; and G4, higher FTI and higher SMI. The associations of the FTI, SMI, and body mass index (BMI) with all-cause mortality were evaluated. During a median follow-up of 2.5 years, 29 patients died. The 5-year survival rates were 48.6%, 76.1%, 95.7%, and 87.4% in the G1, G2, G3, and G4 groups, respectively (P = 0.0002). The adjusted hazard ratio values were 0.34 (95% confidence interval [CI] 0.10-0.95, P = 0.040) for G2 vs. G1, 0.13 (95%CI 0.01-0.69, P = 0.013) for G3 vs. G1, and 0.25 (95%CI 0.07-0.72, P = 0.0092) for G4 vs. G1, respectively. With regard to model discrimination, on adding both FTI and SMI to a model with established risk factors, the C-index increased significantly when compared with the value for a model with BMI (0.763 vs. 0.740, P = 0.016). Higher FTI and/or higher SMI values were independently associated with reduced risks of all-cause mortality in HD patients. Moreover, the combination of the FTI and SMI may more accurately predict all-cause mortality when compared with BMI. Therefore, these body composition indicators should be evaluated simultaneously in this population.

The effect of dulaglutide on body composition in type 2 diabetes mellitus patients on hemodialysis.

AIMS: To evaluate the effect of dulaglutide on body composition in type 2 diabetes mellitus (T2DM) patients undergoing hemodialysis (HD). METHODS: Twenty-one T2DM patients on HD, who had been treated with insulin and newly added teneligliptin (N = 10) or dulaglutide (N = 11), were enrolled. Body composition changes, such as fat mass (FM) and skeletal muscle mass (SMM), glycated albumin (GA), and insulin doses were compared before and after six months of treatment with teneligliptin or dulaglutide. RESULTS: The percentage changes of GA and insulin doses were comparable between the teneliglipin and dulaglutide groups. Conversely, although FM and SMM did not change in the teneligliptin group (from 15.7 kg to 14.1 kg, P = 0.63 and 18.6 kg to 18.9 kg, P = 0.16, respectively), those in the dulaglutide group significantly decreased (from 21.9 kg to 18.9 kg, P = 0.037 and 21.0 kg to 20.2 kg, P = 0.011, respectively). CONCLUSIONS: Six months of dulaglutide treatment significantly reduced not only FM but also SMM, although changes in GA and insulin doses were comparable with those in the teneligliptin group. Dulaglutide may have the effect of promoting sarcopenia; therefore, it may be carefully used in T2DM patients on HD.

The Impact of Abdominal Fat Levels on All-Cause Mortality Risk in Patients Undergoing Hemodialysis.

Although an increased body mass index is associated with lower mortality in patients undergoing hemodialysis (HD), known as the "obesity paradox," the relationship of abdominal fat levels with all-cause mortality has rarely been studied. We investigated the impact of computed-tomography-measured abdominal fat levels (visceral fat area (VFA) and subcutaneous fat area (SFA)) on all-cause mortality in this population. A total of 201 patients undergoing HD were enrolled and cross-classified by VFA and SFA levels according to each cutoff point, VFA of 78.7 cm² and SFA of 93.2 cm², based on the receiver operator characteristic (ROC) curve as following; group 1 (G1): lower VFA and lower SFA, G2: higher VFA and lower SFA, G3: lower VFA and higher SFA, G4: higher VFA and higher SFA. During a median follow-up of 4.3 years, 67 patients died. Kaplan-Meier analysis revealed 10-year survival rates of 29.0%, 50.0%, 62.6%, and 72.4% in G1, G2, G3, and G4 (p < 0.0001), respectively. The adjusted hazard ratio was 0.30 (95% confidence interval [CI] 0.05-1.09, p = 0.070) for G2 vs. G1, 0.37 (95% CI 0.18-0.76, p = 0.0065) for G3 vs. G1, and 0.21 (95% CI 0.07-0.62, p = 0.0035) for G4 vs. G1, respectively. In conclusion, combined SFA and VFA levels were negatively associated with risks for all-cause mortality in patients undergoing HD. These results are a manifestation of the "obesity paradox."

Improved glycemic control with once-weekly dulaglutide in addition to insulin therapy in type 2 diabetes mellitus patients on hemodialysis evaluated by continuous glucose monitoring.

AIMS: To evaluate the efficacy and safety of adding once-weekly dulaglutide to insulin therapy in type 2 diabetes mellitus (T2DM) patients on hemodialysis. METHODS: Fifteen insulin-treated T2DM patients on hemodialysis were enrolled. Continuous glucose monitoring was performed before (1st hospitalization) and after the fifth dulaglutide administration (2nd hospitalization). The insulin dose was reduced after the first administration of dulaglutide (1st hospitalization day 6). Parameters of glycemic control were compared on 1st hospitalization days 4-5, 2nd hospitalization days 3-4, and days 6-7. RESULTS: The median total daily insulin dose was reduced significantly from 12 (12-25) to 0 (0-12) U (p < 0.0001) after treatment with dulaglutide. Mean glucose level on 2nd hospitalization days 3-4 significantly decreased and that on days 6-7 tended to decrease compared with that on 1st hospitalization days 4-5 (median, 8.2 to 6.7 mmol/L, P = 0.006 and 8.2 to 6.9 mmol/L, P = 0.053, respectively). %CV of glucose levels decreased significantly after dulaglutide administration (28.1 to 19.8, P = 0.003 and 28.1 to 21.0, P = 0.019). However, the incidence of hypoglycemia remained unchanged. CONCLUSIONS: Dulaglutide may improve glycemic control and excursion and allow total daily insulin to be reduced without increasing the risk of hypoglycemia in T2DM patients on hemodialysis.

Serum albumin-adjusted glycated albumin as a better indicator of glycemic control in Type 2 diabetes mellitus patients with short duration of hemodialysis.

AIMS: Serum albumin-adjusted glycated albumin (adjusted GA) is reportedly a better predictor of mortality than GA in patients with Type 2 diabetes mellitus (T2DM) on hemodialysis (HD). We compared how accurately GA and adjusted GA reflected glycemic control in these patients. METHODS: We enrolled 31 patients with T2DM on HD. They were divided into two groups according to duration of HD: ≤6months (short HD group, N=16) and >6months (long HD group, N=15). GA or adjusted GA and parameters of glycemic control obtained by continuous glucose monitoring were measured, and the correlations between these were analyzed. RESULTS: GA and adjusted GA were significantly correlated with mean glucose levels (r=0.400, P=0.025 and r=0.508, P=0.0037) in all patients. Similar results were obtained in the long HD group (GA: r=0.554, P=0.032; adjusted GA: r=0.604, P=0.017). However, in the short HD group, adjusted GA (r=0.502, P=0.047) but not GA (r=0.340, P=0.20) was significantly correlated with mean glucose levels. CONCLUSIONS: Adjusted GA may be a better indicator than GA for evaluating glycemic control in T2DM patients with short duration of HD.

Efficacy and safety of teneligliptin in addition to insulin therapy in type 2 diabetes mellitus patients on hemodialysis evaluated by continuous glucose monitoring.

AIMS: Appropriate glycemic control without hypoglycemia is important in patients with type 2 diabetes on hemodialysis. Teneligliptin, a novel dipeptidyl peptidase-4 inhibitor, can be used without dose adjustment for these patients. Using continuous glucose monitoring (CGM), we evaluated the efficacy and safety of adding teneligliptin to insulin therapy. METHODS: Twenty-one type 2 diabetes mellitus patients on hemodialysis treated with insulin were enrolled. After the adjustment of insulin dose, their blood glucose level was monitored by CGM. Insulin dose was reduced after teneligliptin administration. RESULTS: The median total daily insulin dose significantly reduced from 18 (9-24)U to 6 (0-14)U (p<0.0001). Maximum, mean, and standard deviation of blood glucose level on the hemodialysis and non-hemodialysis days did not change after teneligliptin administration. However, minimum blood glucose level was significantly elevated on the hemodialysis day after teneligliptin administration (from 3.9±1.0mmol/L to 4.4±0.9mmol/L, p=0.040). The incidence of asymptomatic hypoglycemia on the hemodialysis day detected by CGM significantly decreased from 38.1% to 19.0% (p=0.049). CONCLUSIONS: Teneligliptin may contribute toward reducing the total daily insulin dose and preventing hypoglycemic events on the hemodialysis day in type 2 diabetes mellitus patients.

Associations of urinary cadmium with circulating sex hormone levels in pre- and postmenopausal Japanese women.

BACKGROUND: Exposure to cadmium has been suspected as a risk factor for breast cancer. The present study examined the associations between urinary cadmium levels and circulating sex hormone levels that are linked to breast cancer risk in healthy women. METHODS: The study subjects were 396 premenopausal Japanese women who had regular menstrual cycles less than 40 days long and 207 postmenopausal Japanese women. Urinary cadmium was measured using spot urine samples. Plasma estradiol, testosterone, and dehydroepiandrosterone sulfate were measured. Additionally, the follicle-stimulating hormone, luteinizing hormone, and sex hormone-binding globulin were measured for premenopausal women. RESULTS: In premenopausal women, the urinary cadmium level either expressed in µg per liter or per g of urine creatinine was significantly inversely associated with total and free testosterone levels after controlling for age, body mass index, smoking status, alcohol intake, and the phase of the menstrual cycle. Total and free testosterone levels were 14.6% and 15.0% lower, respectively, in women in the highest quartile of urinary cadmium per g creatinine in those in the lowest quartile. In postmenopausal women, the urinary cadmium in µg per liter as well as per g creatinine was significantly inversely associated with the estradiol level after controlling for covariates. The estradiol level was 25.8% lower in women in the highest tertile of urinary cadmium per g creatinine than in those in the lowest tertile. CONCLUSIONS: The data suggest inverse associations between urinary cadmium and the plasma estradiol or testosterone level in Japanese women.

Acidosis-Induced Hypochloremic Alkalosis in Diabetic Ketoacidosis Confirmed by The Modified Base Excess Method.

CONTEXT AND OBJECTIVE: Diabetic ketoacidosis (DKA) is associated with a metabolic alkalosis, which is thought to be due to vomiting. However, alkalosis can occur in DKA without vomiting. We retrospectively reviewed the acid-base disturbances in DKA admissions without vomiting. PARTICIPANTS AND METHODS: We included admissions of the patients with blood glucose and beta-hydroxybutyrate (ßOHB) levels > 250 mg/dL and > 1.0 mmol/L, respectively. Admissions without vomiting were classified into a group with a ßOHB > 3.0 mmol/L (DKA group) and a group with ßOHB of 1.0-3.0 mmol/L (pre-DKA group). The acid-base status was analyzed by the modified base excess (BE) method. BE effects were calculated by changes in sodium (BE free water, [BEFW]), and chloride (BECl). Positive and negative values for each parameter suggested alkalosis and acidosis, respectively. RESULTS: Forty-five included admissions were divided into DKA (n = 34) and pre-DKA (n =11) groups. Sodium-corrected chloride level and the chloride/sodium ratio were significantly lower in the DKA group than in the pre-DKA group. In both groups, BEFW values were modestly negative. The mean BECl values were positive in both groups, but significantly higher in the DKA group. The alkalinizing effects by hypochloremia diminished the base deficit in the DKA group by approximately 25%. The BECl value significantly correlated with serum total ketone levels (r = 0.66; P < .0001). CONCLUSION: The modified BE method successfully proved the presence of hypochloremic alkalosis in DKA without vomiting. This suggests the direct participation of serum ketoacids in the pathogenesis of hypochloremic alkalosis.

Serum albumin-adjusted glycated albumin is a better predictor of mortality in diabetic patients with end-stage renal disease on hemodialysis.

AIMS: Glycated albumin (GA) is a marker for monitoring glycemic control in diabetic patients with end-stage renal disease (ESRD). We evaluated whether serum albumin-adjusted GA (adjusted GA) could predict mortality in diabetic patients with ESRD on hemodialysis. METHODS: Seventy-eight patients with type 2 diabetes treated with regular hemodialysis were enrolled and followed up for 5-years. The adjusted GA was calculated from the regression formula and mean GA. The cut-off values for GA and adjusted GA that predicted mortality risk were determined using receiver operating characteristic curve analysis. RESULTS: During the follow-up period (median: 36months), 15 patients died. In the Kaplan-Meier analysis, there were no significant differences in the 5-year cumulative survival rate (58.3% [GA ≥19.8%] vs. 88.6% [GA <19.8%], P=0.075). Conversely, this rate was significantly higher in patients with adjusted GA <21.2% than adjusted GA ≥21.2% (86.4 vs. 49.5%, P=0.0068). After adjustment for other confounders, adjusted GA ≥21.2% was an independent predictor for mortality (hazard ratio 3.76, 95% confidence interval 1.12-17.44, P=0.031), but GA ≥19.8% was not (hazard ratio 2.63, 95% confidence interval 0.65-17.69, P=0.19). CONCLUSIONS: Adjusted GA is a better predictor of mortality than GA in diabetic patients with ESRD on hemodialysis.

Clinical benefits of metformin in gynecologic oncology.

Evidence has suggested that diabetes may contribute to the initiation and progression of specific types of cancer. Metformin, a biguanide, has become the preferred first-line therapy for the treatment of type 2 diabetes. Metformin is inexpensive, has a proven safety profile and is able to be safely combined with additional antidiabetic agents. In addition to the well-established antidiabetic effects of metformin, there has also been notable interest in its antitumor properties. The present review discusses the emerging role of metformin as an example of an existing drug, used worldwide in the treatment of diabetes, which has been demonstrated to exert significant in vitro and in vivo anticancer activities and has thus been investigated in clinical trials. In gynecologic oncology, metformin has been suggested to exhibit significant treatment efficacy against endometrial cancer. Three studies have demonstrated the potential therapeutic effects of metformin on the survival outcome of patients with ovarian cancer and in ovarian cancer prevention. However, this evidence was based on observational studies. Metformin has been shown to exert no statistically significant beneficial effect on cervical cancer incidence or mortality. By cancer site, the current limited insights highlight the need for clinical investigations and better-designed studies, along with evaluation of the effects of metformin on cancer at other sites.

Association of hair dye use with circulating levels of sex hormones in premenopausal Japanese women.

BACKGROUND: Substances identified as animal carcinogens are no longer used as ingredients of hair dyes. However, hair dyes are diverse groups of chemicals, and certain compounds may affect endogenous sex hormone levels. We examined the association between hair dye use and sex hormone levels among premenopausal women. METHODS: Study subjects were 431 premenopausal Japanese women who had regular menstrual cycles less than 40 days long. Information on the use of hair dyes or hair bleach, the type of hair coloring used, the duration of use and the frequency of application was collected using a self-administered questionnaire. Fasting plasma samples were obtained to measure estradiol, testosterone, dehydroepiandrosterone sulfate, sex hormone-binding globulin, follicle-stimulating hormone and luteinizing hormone. RESULTS: After controlling for covariates, the mean plasma total testosterone level was about 14% higher in women who had used hair dyes for 10 or more years than that among women who had never used them (P for trend = 0.02). A similar association was observed when the type of hair dye was restricted to permanent hair dyes. A higher frequency of applying non-permanent hair dyes was marginally significantly associated with higher total and free estradiol levels. CONCLUSIONS: Data suggest that long-term use of hair dyes may be associated with an increase in circulating testosterone levels. As this is, to our knowledge, the first study examining the association between hair dye use and sex hormone levels, replication of the results is required.

Associations of acrylamide intake with circulating levels of sex hormones and prolactin in premenopausal Japanese women.

BACKGROUND: It has been hypothesized that alteration of hormone systems is involved in the carcinogenesis of acrylamide. The aim of the present study was to examine the cross-sectional associations between dietary acrylamide intake and sex hormone levels in premenopausal Japanese women. METHODS: Study subjects were 393 women who had regular menstrual cycles less than 40 days long. Acrylamide intake was assessed with a food-frequency questionnaire and was based on acrylamide concentration reported from analyses of Japanese foods. We measured the plasma concentrations of estradiol, testosterone, dehydroepiandrosterone sulfate, sex hormone-binding globulin, follicle-stimulating hormone, luteinizing hormone, and prolactin. RESULTS: After controlling for age, the phase of the menstrual cycle, and other covariates, acrylamide intake was statistically significantly inversely associated with total and free estradiol levels and statistically significantly positively associated with follicle-stimulating hormone level. Total and free estradiol levels were 18.2% and 19.3% lower, respectively, in women in the highest quartile of acrylamide intake than in those in the lowest quartile of intake. Follicle-stimulating hormone levels were 23.5% higher in women in the highest quartile of acrylamide intake than in those in the lowest quartile of intake. CONCLUSION: The data suggest that acrylamide intake may alter estradiol and follicle-stimulating hormone levels. IMPACT: High estradiol levels have been associated with an increased risk of breast cancer. Although the results need confirmation, they highlight the need to investigate the relationships among dietary acrylamide, sex hormones, and breast cancer risk. Cancer Epidemiol Biomarkers Prev; 24(1); 249-54. ©2014 AACR.

Association of cigarette smoking with skin colour in Japanese women.

OBJECTIVES: Having a lighter skin tone is highly valued among many Asian women. If skin colour is affected by smoking, women may be motivated to avoid tobacco or quit smoking. The present study examined the association of tobacco smoking with skin colour in Japanese women. METHOD: Information on smoking habits was obtained through a self-administered questionnaire completed by 939 Japanese women aged 20-74 in Gifu, Japan, during 2003-2006. Skin colour was examined on the inner side of the upper and lower arm and on the forehead using a Mexameter device (a narrow-band reflective spectrophotometer), which expressed results as a melanin index and erythema index. RESULTS: Current smokers had higher melanin indices than never-smokers and former smokers for all measured sites. The number of cigarettes smoked per day, the years of smoking and pack-years were significantly positively associated with melanin indices for all measured sites after adjustments for age, body mass index, lifetime sun exposure, and room temperature and humidity. Smoking was also significantly associated with erythema indices on the inner upper and lower arms. CONCLUSIONS: These data suggest that smoking is associated with a darker skin colour. If our findings are confirmed by further studies, they could be used in antismoking campaigns or by smoking cessation services.