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.

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.

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.

Plasma amino acid profiles are associated with biomarkers of breast cancer risk in premenopausal Japanese women.

OBJECTIVE: Recently, profiles of plasma amino acids have been utilized to detect diseases including breast cancer. However, there is a possibility that the amino acid status may be associated with the risk of breast cancer. We investigated the relationship of plasma levels of amino acids with levels of sex hormones and insulin-like growth factor (IGF)-1, which are relevant to the etiology of premenopausal breast cancer, in normal premenopausal women. METHODS: Participants were 350 Japanese women who had regular menstrual cycles less than 40-day long. Fasting plasma samples were assayed for estradiol, testosterone, dehydroepiandrosterone sulfate, sex-hormone-binding globulin (SHBG), and IGF-1. A total of 20 amino acids in plasma were quantified by liquid chromatography-mass spectrometry. Information on lifestyle and reproductive factors was obtained using a self-administered questionnaire. RESULTS: The plasma arginine level was significantly inversely correlated with plasma levels of total and free estradiol and IGF-1 after adjusting for age, body mass index, and phase of the menstrual cycle. Plasma leucine and tyrosine levels were significantly positively correlated with the free testosterone level. The ratio of plasma asparagine to the total amino acids was significantly positively correlated with SHBG level. CONCLUSIONS: Plasma levels of some specific amino acids, such as arginine, leucine, tyrosine, and asparagine, were associated with the levels of sex hormones, SHBG, or IGF-1 in premenopausal women. However, the present cross-sectional study cannot provide a cause-effect relation. The implication of amino acids in the etiology of breast cancer needs to be addressed in future studies.

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.

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.

Associations of intakes of fat, dietary fiber, soy isoflavones, and alcohol with levels of sex hormones and prolactin in premenopausal Japanese women.

OBJECTIVE: Endogenous sex hormones have been implicated in the etiology of breast cancer. Dietary factors such as fat, dietary fiber, soy isoflavones, and alcohol have been suggested to influence endogenous estrogen and other steroid hormone levels. We examined the relationship among these dietary factors and plasma sex hormone levels in premenopausal Japanese women. METHODS: We measured the plasma concentrations of estradiol, estrone, testosterone, dehydroepiandrosterone sulfate, sex hormone-binding globulin, a follicle-stimulating hormone, a luteinizing hormone, and prolactin among 393 premenopausal women who had regular menstrual cycles fewer than 40 days apart. The dietary intakes were estimated with a validated food frequency questionnaire. RESULTS: After controlling for age, BMI, phase of the menstrual cycle, number of births, age at first birth, history of breastfeeding, and smoking status, the saturated fat intake was significantly positively associated with total estradiol and free estradiol levels. Intakes of the other types of fat, dietary fiber, soy isoflavones, and alcohol were not significantly associated with levels of any hormone measured. CONCLUSIONS: These data suggest that a high intake of saturated fat is associated with increased estradiol levels in premenopausal Japanese women. Saturated fat intake may have implications in the etiology of breast cancer.

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.

Associations of body size and reproductive factors with circulating levels of sex hormones and prolactin in premenopausal Japanese women.

OBJECTIVE: Body size and reproductive factors are important risk factors of breast cancer. The aim of the present study was to examine the associations of these factors with blood concentrations of sex hormones and prolactin in premenopausal Japanese women. METHODS: We measured the plasma concentrations of estradiol, estrone, testosterone, dehydroepiandrosterone sulfate (DHEAS), sex hormone-binding globulin (SHBG), follicle-stimulating hormone, luteinizing hormone, and prolactin among 436 women who had regular menstrual cycles less than 40 days long. Information on menstrual and reproductive factors including history of breastfeeding was obtained using a self-administered questionnaire. Height and weight were measured. RESULTS: After controlling for age and the phase of the menstrual cycle, the body mass index (BMI) was significantly inversely associated with total estradiol, estrone and SHBG and significantly positively associated with total and free testosterone and DHEAS. Nulliparous women had significantly higher levels of total and free testosterone, DHEAS, and prolactin than parous women. Duration of breastfeeding for the first child was significantly inversely associated with free testosterone and prolactin levels. CONCLUSIONS: The data suggest that an increased risk of premenopausal breast cancer associated with low BMI is partially mediated by an increased total estradiol. Androgens and prolactin may explain the breast cancer protection provided by giving birth and breastfeeding.

Association of dietary fat, vegetables and antioxidant micronutrients with skin ageing in Japanese women.

Daily diet may have implications for skin ageing. However, data on the relationship between diet and the parameters of skin conditions are scarce. The present study aimed to examine the associations of biophysical properties of the skin of women with intakes of fats and antioxidant micronutrients as well as food groups as sources of these nutrients. In a cross-sectional study, we measured the hydration, surface lipids and elasticity of the skin of 716 Japanese women using non-invasive techniques. The extent of facial wrinkles in the crow's-foot area was determined by observation using the Daniell scale. Each subject's usual diet was determined with the use of a validated FFQ. After controlling for covariates including age, smoking status, BMI and lifetime sun exposure, the results showed that higher intakes of total fat, saturated fat and monounsaturated fat were significantly associated with increased skin elasticity. A higher intake of green and yellow vegetables was significantly associated with a decreased Daniell wrinkling score. Intake of saturated fat was significantly inversely associated with the Daniell wrinkling score after additional adjustment for green and yellow vegetable intake. Further studies with more accurate measurement methods are needed to investigate the role of daily diet in skin ageing.

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.

Association of intakes of fat, dietary fibre, soya isoflavones and alcohol with uterine fibroids in Japanese women.

Certain dietary components which could affect oestrogen may have implications in the aetiology of uterine fibroids. We previously found that soya intake was inversely associated with a subsequent risk of hysterectomy, suggesting a potentially protective effect of soya against uterine fibroids, the major clinical indication for hysterectomy. We cross-sectionally assessed the associations of intakes of fat, soya foods, dietary fibre and alcohol with uterine fibroids. Study subjects were 285 premenopausal Japanese women participating in a health-check up programme, including gynaecological examinations, provided by a general hospital between October 2003 and March 2006. The presence of fibroids was confirmed by transvaginal sonogram. If women had undergone hysterectomy, self-report of fibroids was accepted. Each subject's usual diet, including alcohol, was determined with the use of a validated FFQ. Fifty-four women were identified as prevalent cases of fibroids or having had hysterectomy due to fibroids. The mean alcohol intake was statistically significantly higher among women with fibroids than among those without fibroids after controlling for known or suspected risk factors. For the highest compared with the lowest tertile of alcohol intake, the OR of uterine fibroids was 2.78 (95% CI 1.25, 6.20). There was no significant association of intake of fats, soya isoflavones or dietary fibre with uterine fibroids. The data suggest that higher alcohol intake is associated with a higher prevalence of uterine fibroids. Further studies on diet, especially phyto-oestrogens, and uterine fibroids are needed given the limited data currently available.

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 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."

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.

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.

Circulating insulin-like growth factor-1 and insulin-like growth factor binding protein-3 are associated with early carotid atherosclerosis.

OBJECTIVE: Growth hormone (GH)-insulin-like growth factor (IGF)-1 axis regulates growth and survival of vascular cells and cardiomyocytes. The role of GH-IGF-1 axis in cardiovascular disease is controversial. METHODS AND RESULTS: We assessed the association of circulating levels of IGF-1 and IGF binding protein-3 (IGFBP-3) with early carotid atherosclerosis and atherosclerotic risk factors in 330 Japanese men (age 51.6+/-8.6 years, range 29 to 77, body mass index [BMI] 23.6+/-2.9 kg/m2). Intima-media thickness (IMT) of the common carotid artery was measured by ultrasound. Abdominal visceral adipose and subcutaneous adipose tissue area by computer-assisted tomographic scan were determined. Correlation coefficients were calculated by partial correlation analysis. BMI and plasma insulin showed positive associations with circulating IGF-1 and IGFBP-3. Subcutaneous adipose tissue was correlated with IGF-1. High-density lipoprotein cholesterol was inversely associated with IGF-1. Blood pressure, total cholesterol, triglyceride, and visceral adipose tissue were positively associated with IGFBP-3. IGF-1 and IGFBP-3 were associated with carotid IMT independent of age, BMI, blood pressure, and insulin. Insulin was associated with carotid IMT in univariate analysis. However, it was not correlated with carotid IMT in the multivariate analyses which included IGF-1 or IGFBP-3 as a covariate. CONCLUSIONS: Increased circulating IGF-1 and IGFBP-3 may be stimulators of atherosclerosis.