Fasting Morning Research Articles

Early start of growth hormone is associated with positive effects on auxology and metabolism in Prader-Willi-syndrome

BackgroundPrader-Willi-Syndrome (PWS) is characterized by hypothalamic-pituitary dysfunction. Recent research suggests starting growth hormone-treatment (GHT) as soon as possible. The aim of this study is to analyze possible differences in auxological parameters, carbohydrate and lipid metabolism between two groups of children with PWS that started GHT either during or after their first year of life.Study designRetrospective longitudinal study of 62 children (31 males) with genetically confirmed PWS. Upon diagnosis all children were offered GHT, some started immediately, others commenced later. Cohort A (n = 21; 11 males) started GHT at 0.3–0.99 yrs. (mean 0.72 yrs) and Cohort B (n = 41; 20 males) commenced GHT at 1.02–2.54 yrs. (mean 1.42 yrs) of age. Fasting morning blood samples and auxological parameters were obtained before the start of therapy and semi-annually thereafter. Differences between the two cohorts were estimated with a linear mixed-effect model.ResultsMean length/height-SDSPWS differed significantly between the groups [1 yr: A: 0.37 (±0.83) vs B: 0.05 (±0.56); 5 yrs.: A: 0.81 (±0.67) vs B: 0.54 (±0.64); p = 0.012]. No significant differences were found in BMI, lean body mass or body fat.Low-density cholesterol was significantly lower in A than in B [LDL: 1 yr: A: 79 (±20) mg/dl vs B: 90 (±19) mg/dl; 5 yrs.: A: 91(±18) mg/dl vs 104 (±26) mg/dl; p = 0.024].We found significant differences in the glucose homeostasis between the groups [fasting insulin: p = 0.012; HOMA-IR: p = 0.006; HbA1c: p < 0.001; blood glucose: p = 0.022].ConclusionsAn early start of GHT during the first year of life seems to have a favorable effect on height-SDS and metabolic parameters.

Associations of ozone exposure with urinary metabolites of arachidonic acid

BackgroundOzone (O3) exposure has been associated with biomarkers of platelet activation and oxidative stress. The metabolism of arachidonic acid (AA) plays an important role in platelet activation and oxidative stress. However, AA metabolic pathways have not been examined in relation to O3 and other air pollutants. MethodsEarly morning urine and fasting blood were longitudinally collected up to four times from 89 healthy adults (22–52 years old, 25 women) in Changsha City, China. We measured three urinary AA metabolites, namely 11-dehydro-Thromboxane B2 (11-dhTXB2) produced from the arachidonic cyclooxygenase pathway, 20-hydroxyeicosatetraenoic acid (20-HETE) from the CYPs pathway, and 8-isoprostane from the non-enzymatic pathway. Urinary malondialdehyde (MDA) and 8-hydroxy-2′-deoxyguanosine (8-OHdG) were measured as indicators of oxidative damage to lipids and DNA, respectively. We measured soluble P-selectin (sCD62p) concentrations in plasma as an indicator of platelet activation. Indoor and outdoor air pollutants were measured and combined with participants’ time-activity pattern to calculate personal exposure to O3, PM2.5, NO2, and SO2 averaged over 12-hour, 24-hour, 1-week, and 2-week periods prior to biospecimen collection, respectively. Linear mixed-effects models were used to examine the relationships of AA metabolites with air pollutant exposures, plasma sCD62p, and urinary MDA & 8-OHdG. ResultsWe found that a 10% increase in 12 h and 24 h O3 exposure were associated with increases in urinary11-dhTXB2 by 1.4% (95%, 0.1% to 2.6%) and 1.3% (0.05% to 2.5%), respectively. These associations remained robust after adjusting for co-pollutant exposures. No significant associations were observed between 11-dhTXB2 and other pollutants or between O3 exposures and other AA metabolites. All the three AA metabolites were significantly and positively associated with urinary MDA and 8-OHdG, whereas only urinary 11-dhTXB2 was significantly and positively associated with plasma sCD62p. ConclusionsA metabolite of AA from the cyclooxygenase pathway was positively associated with short-term O3 exposure, and with a plasma marker of platelet activation and two urinary markers of oxidative stress. The results suggest that O3 exposure may contribute to increased platelet activation and oxidative damages via altering the metabolism of AA.

Associations of estimated 24-h urinary sodium excretion with mortality and cardiovascular events in Chinese adults: a prospective cohort study.

To investigate the associations of sodium excretion with blood pressure, mortality and cardiovascular diseases in Chinese population. We studied 39 366 individuals aged 35-70 years from 115 urban and rural communities in 12 centers across mainland China. Trained research staff conducted face-to-face interview to record baseline information of all participants based on questionnaires, and collected their morning fasting urine samples to estimate 24-h sodium excretion (24hUNaE). Multivariable frailty Cox regression accounting for clustering by centre was performed to examine the association between estimated 24hUNaE and the primary composite outcome of death and major cardiovascular events in a Chinese population. Mean 24hUNaE was 5.68 (SD 1.69) g/day. After a median follow-up of 8.8 years, the composite outcome occurred in 3080 (7.8%) participants, of which 1426 (3.5%) died and 2192 (5.4%) suffered from cardiovascular events. 24hUNaE was positively associated with increased SBP and DBP. Using the 24hUNaE level of 4-4.99 g/day as the reference group, a 24hUNaE of either lower (<3 g/day) or higher (≥7 g/day) was associated with an increased risk of the composite outcome with a hazard ratio of 1.22 (95% confidence interval: 1.01-1.49) and 1.15 (95% confidence interval: 1.01-1.30), respectively. A similar trend was observed between 24hUNaE level and risk of death or major cardiovascular events. These findings support a positive association between estimated urinary sodium excretion and blood pressure, and a possible J-shaped pattern of association between sodium excretion and clinical outcomes, with the lowest risk in participants with sodium excretion between 3 and 5 g/day.

Noninvasive evaluation of diabetic patients with high fasting blood glucose using DWI and BOLD MRI.

To investigate the renal microstructure changes and hypoxia changes in type 2 diabetic patients and the relationship between them and glucose using both diffusion-weighted imaging (DWI) and blood oxygenation level-dependent magnetic resonance imaging (BOLD MRI). After measuring morning fasting blood glucose, DWI and BOLD MRI were performed in 57 patients with type 2 diabetes mellitus (DM group) and 14 healthy volunteers (NC group). According to the fasting blood glucose levels, diabetic patients were divided into a normoglycemic diabetes group (group A), a less hyperglycemic diabetes group (group B) and a more hyperglycemic diabetes group (group C). The renal parenchymal apparent diffusion coefficient (ADC), renal cortical R2* (CR2*), and medullary R2* (MR2*) were measured, and the R2* ratio between the medulla and cortex (MCR) was calculated. To test for differences in ADC, R2*, and MCR among the four groups, the data were analyzed by separate one-way ANOVAs. The correlations between ADC, R2*, and MCR and the clinical index of renal function were analyzed. Groups B and C had significantly lower ADC values in the renal parenchyma (P = 0.048, 0.002) and significantly higher MR2* and MCR values (P < 0.000, P = 0.001, 0.001, and 0.005, respectively) than the NC group. ADC was negatively correlated with glucose, and MR2*, MCR and glucose showed a weak positive correlation. DWI and BOLD may indirectly and qualitatively reflect the kidney microstructure status and hypoxia level of diabetic patients at different blood glucose levels to a certain extent, and possibly guide the clinical treatment of diabetic patients with different blood glucose levels.

Serum osteocalcin is associated with subjective stress in people with depression and type 2 diabetes

BackgroundLow serum osteocalcin is a risk factor for type 2 diabetes mellitus (T2DM), and osteocalcin release from bone is associated with an acute stress response in mice. Both diabetes and stress are associated with depression. Here, we assess relationships between serum osteocalcin, depression and subjective stress in people with T2DM. MethodsParticipants with T2DM (HbA1c above 6.4 %, impaired fasting glucose or impaired glucose tolerance) were assessed for a major depressive episode using the research version of the Structured Clinical Interview for DSM-5 depression criteria (SCID-5RV). Subjective stress over the past month was assessed using the Perceived Stress Scale (PSS). Serum carboxylated (cOCN) and fully decarboxylated (dcOCN) osteocalcin were assayed from fasting morning blood by commercial enzyme-linked immunosorbent assay. ResultsAmong 95 participants (mean age 62.4 ± 9.9, 51 % women), 22 % were experiencing a depressive episode (9 men, 12 women). The presence of a depressive episode was not associated with dcOCN or cOCN concentrations; however, higher concentrations of cOCN were associated with higher PSS scores in participants with depression (r = 0.585, p = 0.005). In an analysis of covariance model controlling for age, sex, body mass index, glycemic control (glycosylated hemoglobin), insulin resistance (homeostatic model), depression, and antidepressant use, cOCN was associated with PSS scores (F=10.302, p = 0.002), and this relationship was stronger in those with depression (depression × cOCN interaction F=4.978, p = 0.028). Although associations between dcOCN concentrations and PSS scores did not reach significance, the same trend seen with cOCN concentrations was observed in participants with depression for dcOCN (r=0.365, p=0.10), and for a depression × dcOCN interaction associated with PSS scores in the whole group (F=2.165, p = 0.15). ConclusionsOsteocalcin is a neuroendocrine marker associated with perceived chronic stress among people with T2DM experiencing a depressive episode.

Preliminary Investigation to Review If a Glycomacropeptide Compared to L-Amino Acid Protein Substitute Alters the Pre- and Postprandial Amino Acid Profile in Children with Phenylketonuria.

In Phenylketonuria (PKU), the peptide structure of the protein substitute (PS), casein glycomacropeptide (CGMP), is supplemented with amino acids (CGMP-AA). CGMP may slow the rate of amino acid (AA) absorption compared with traditional phenylalanine-free amino acids (Phe-free AA), which may improve nitrogen utilization, decrease urea production, and alter insulin response. Aim: In children with PKU, to compare pre and postprandial AA concentrations when taking one of three PS’s: Phe-free AA, CGMP-AA 1 or 2. Methods: 43 children (24 boys, 19 girls), median age 9 years (range 5–16 years) were studied; 11 took CGMP-AA1, 18 CGMP-AA2, and 14 Phe-free AA. Early morning fasting pre and 2 h postprandial blood samples were collected for quantitative AA on one occasion. A breakfast with allocated 20 g protein equivalent from PS was given post fasting blood sample. Results: There was a significant increase in postprandial AA for all individual AAs with all three PS. Postprandial AA histidine (p < 0.001), leucine (p < 0.001), and tyrosine (p < 0.001) were higher in CGMP-AA2 than CGMP-AA1, and leucine (p < 0.001), threonine (p < 0.001), and tyrosine (p = 0.003) higher in GCMP-AA2 than Phe-free AA. This was reflective of the AA composition of the three different PS’s. Conclusions: In PKU, the AA composition of CGMP-AA influences 2 h postprandial AA composition, suggesting that a PS derived from CGMP-AA may be absorbed similarly to Phe-free AA, but this requires further investigation.

Effect of obesity therapy in women of reproductive age on leptin level and hormonal ovarian function

Hypothesis/aims of study. Ovarian insufficiency is present in more than 30% of reproductive-age obese women. The role of leptin in the pathogenesis of ovarian insufficiency is not yet established and has to be clarified. It is of interest to study the effect of obesity therapy on hyperleptinemia, hormonal and ovulatory function in reproductive-age women with alimentary obesity. The aim of this study was to assess the effect of obesity therapy on leptin level and hormonal ovarian function in women of reproductive age.&#x0D; Study design, materials and methods. All studied women underwent a clinical and laboratory examination, including: medical history, anthropometry (height and weight measurement, waist and hip circumferences, body mass index calculation), blood pressure measurement, gynecological examination, ultrasound examination of the pelvic organs, osteodensitometry, determination of serum gonadotropins, sex hormones, insulin, leptin, and blood biochemical parameters, morning fasting blood glucose, and glucose after the glucose tolerance test. The survey and objective examination data were recorded in a specially developed application form, including the following parameters: the patients age, menarche age, the type of the menstrual cycle, data on pregnancies, childbirth and reproductive plans, gynecological and somatic diseases.&#x0D; Results. The relationship between the initial levels of leptin, estradiol, HOMA-IR, the number of follicles in the ovaries and the restoration of ovulatory function after the weight loss was revealed. The analysis produced a mathematical model to estimate the predictive value of these indicators in relation to the recovery of ovulation after the weight loss. An analysis was made of the effectiveness of drugs used to treat excess body weight (metformin and sibutramine).&#x0D; Conclusion. The predictive value of the baseline levels of leptin and estradiol, the number of antral follicles and insulin resistance in relation to the achievement of ovulation after the reduction of body weight in patients with anovulation caused by excess body weight and obesity has been established. Ovulation recovery did not depend on the choice of a drug used to treat excess body weight. When comparing the groups of women who received medication for alimentary obesity using metformin and sibutramine, no significant differences in the frequency of ovulation recovery were found.

Type B insulin resistance syndrome associated with connective tissue disease and psoriasis.

SummaryType B insulin resistance syndrome (TBIR) is characterised by the rapid onset of severe insulin resistance due to circulating anti-insulin receptor antibodies (AIRAs). Widespread acanthosis nigricans is normally seen, and co-occurrence with other autoimmune diseases is common. We report a 27-year-old Caucasian man with psoriasis and connective tissue disease who presented with unexplained rapid weight loss, severe acanthosis nigricans, and hyperglycaemia punctuated by fasting hypoglycaemia. Severe insulin resistance was confirmed by hyperinsulinaemic euglycaemic clamping, and immunoprecipitation assay demonstrated AIRAs, confirming TBIR. Treatment with corticosteroids, metformin and hydroxychloroquine allowed withdrawal of insulin therapy, with stabilisation of glycaemia and diminished signs of insulin resistance; however, morning fasting hypoglycaemic episodes persisted. Over three years of follow-up, metabolic control remained satisfactory on a regimen of metformin, hydroxychloroquine and methotrexate; however, psoriatic arthritis developed. This case illustrates TBIR as a rare but severe form of acquired insulin resistance and describes an effective multidisciplinary approach to treatment.Learning points:We describe an unusual case of type B insulin resistance syndrome (TBIR) in association with mixed connective tissue disease and psoriasis.Clinical evidence of severe insulin resistance was corroborated by euglycaemic hyperinsulinaemic clamp, and anti-insulin receptor autoantibodies were confirmed by immunoprecipitation assay.Treatment with metformin, hydroxychloroquine and methotrexate ameliorated extreme insulin resistance.

Endogenous melatonin mediation of systemic inflammatory responses to ozone exposure in healthy adults

Background/aimMelatonin is a free radical scavenger and an anti-inflammatory biomolecule. Air pollution exposure has been associated with increased inflammatory responses. We hypothesize that endogenous melatonin plays a role in inflammatory responses to air pollution exposure. MethodsWe tested this hypothesis in a cohort of 53 healthy adults (22–52 years old, 16 women), none of whom were on melatonin supplementation. Early morning urine and fasting blood were collected from each participant longitudinally up to three times. We analyzed urinary 6-sulfatoxymelatonin (aMT6s), as a surrogate of circulating melatonin, and pro- and anti-inflammatory cytokines in the plasma samples. Indoor and outdoor air pollutants were measured and combined with participants' time-activity patterns to calculate personal exposure to O3, PM2.5, NO2, and SO2 averaged over 12-hour, 24-hour, 1-week, and 2-week periods prior to biospecimen collection, respectively. Linear mixed-effects models were used to examine the relationships among urinary aMT6s, personal pollutant exposure, and plasma cytokines. A mediation analysis was conducted to examine the role of aMT6s in the relationships between pollutant exposures and inflammatory cytokines. ResultsOne interquartile range (4.2 ppb) increase in 2-week O3 exposure was associated with a ‐26.2% (95% CI: −43.9% to −2.8%) decrease in aMT6s. Within the range of endogenous aMT6s concentrations (0.5–53.0 ng/ng creatinine) across the participants, increased aMT6s was associated with decreased pro-inflammatory cytokines including IL-1β, IL-8, IL-17A, IFN-γ, and TNF-α. These cytokines were significantly and positively associated with 2-week average O3 exposure. Furthermore, 7.4% to 17.4% of the O3-cytokine associations were mediated by aMT6s. We did not find similar effects for the other pollutants. ConclusionsPro-inflammatory responses to O3 exposure in the preceding 2 weeks partly resulted from the depletion of endogenous melatonin by O3.

Fasting Status and Circadian Variation Must be Considered When Performing AUC-based Therapeutic Drug Monitoring of Tacrolimus in Renal Transplant Recipients.

Therapeutic drug monitoring (TDM) is mandatory for the immunosuppressive drug tacrolimus (Tac). For clinical applicability, TDM is performed using morning trough concentrations. With recent developments making tacrolimus concentration determination possible in capillary microsamples and Bayesian estimator predicted area under the concentration curve (AUC), AUC‐guided TDM may now be clinically applicable. Tac circadian variation has, however, been reported, with lower systemic exposure following the evening dose. The aim of the present study was to investigate tacrolimus pharmacokinetic (PK) after morning and evening administrations of twice‐daily tacrolimus in a real‐life setting without restrictions regarding food and concomitant drug timing. Two 12 hour tacrolimus investigations were performed; after the morning dose and the following evening dose, respectively, in 31 renal transplant recipients early after transplantation both in a fasting‐state and under real‐life nonfasting conditions (14 patients repeated the investigation). We observed circadian variation under fasting‐conditions: 45% higher peak‐concentration and 20% higher AUC following the morning dose. In the real‐life nonfasting setting, the PK‐profiles were flat but comparable after the morning and evening doses, showing slower absorption rate and lower AUC compared with the fasting‐state. Limited sampling strategies using concentrations at 0, 1, and 3 hours predicted AUC after fasting morning administration, and samples obtained at 1, 3, and 6 hours predicted AUC for the other conditions (evening and real‐life nonfasting). In conclusion, circadian variation of tacrolimus is present when performed in patients who are in the fasting‐state, whereas flatter PK‐profiles and no circadian variation was present in a real‐life, nonfasting setting.

Serum Melatonin with Respect to Mental Health (Anxiety &amp; Depression) Status of First Year M.B.B.S Students

Introduction: Melatonin is a pineal hormone secreted in circadian manner, with a peak during evening and night. Night-time light exposure is a powerful suppressor of nocturnal melatonin secretion. Dopamine and serotonin have complex relationship in melatonin synthesis and secretion. Reduced levels of melatonin have been associated with severe depression. Melatonin exhibits GABA-like effects may be responsible to reduce anxiety.&#x0D; Objectives: To determine the Serum Melatonin levels with respect to bedtime and its correlation with the severity of anxiety and depression. Also, to find the difference in anxiety score, depression score and serum melatonin level with respect to gender.&#x0D; Methods: A cross sectional study was done amongst first year medical students, and anxiety and depression score was calculated using Hamilton’s anxiety and depression scale. Estimation of Serum Melatonin was done on the fasting morning blood samples.&#x0D; Results and Conclusion: The present study shows that there is no significant difference in melatonin secretion in the students with late bedtime. With the increasing severity of the anxiety the serum melatonin was found to be lower, but the difference was not statistically significant. Similar results were observed with depression. The results shows non-significant higher anxiety and depression scores in females as compared to males. The study results also shows the significant high levels of melatonin in males as compared to females. Low melatonin levels in females may be attributed to high anxiety and depression in females.

Obstructive sleep apnea is not an independent determinant of testosterone in men.

Obstructive sleep apnea (OSA) is generally considered to lower serum testosterone concentration in men, although data supporting this as a direct effect are limited. The aim of this study was to determine the relationship between the presence and severity of OSA and testosterone in a community-based cohort of men aged over 40 years. Anthropometry, polysomnography and biomedical information were collected from enrolled, consenting men from the prospective, longitudinal MAILES study cohort. Fasting morning blood samples (n = 1869) were drawn between 2010 and 2012 for measurement of testosterone using liquid chromatography mass spectrometry. Home polysomnography was completed in 861 men between 2010 and 2012. The final analysis sample consisted of 623 men aged 41-86 years. The effect of OSA on testosterone were analyzed using linear regression models controlling for potential confounders (age, BMI and sex hormone binding globulin (SHBG)). The mean (s.d.) cohort characteristics were: age 59.0 (10.2) years, testosterone 16.8 (5.3) nmol/L, SHBG 32.9 (13.1) nmol/L, BMI 28.6 (4.2) kg/m2 and apnoea hypopnoea index (AHI) 14.9 (13.7). OSA was present in 51.5%. There was an inverse relationship between AHI and testosterone (P = 0.01), which was lost after covariate adjustment. These data suggest that obesity, rather than OSA per se, determine testosterone concentration. This accords with the graded effect of weight loss, but limited effect of continuous positive airway pressure to increase testosterone, and highlights the importance of managing obesity in men with low testosterone concentration, particularly in the context of OSA.

Cognitive behavioural therapy for insomnia does not appear to have a substantial impact on early markers of cardiovascular disease: A preliminary randomized controlled trial.

According to the World Health Organization, cardiovascular diseases are the leading cause of death in the world. Therefore, early prevention of these diseases is a public health priority. Epidemiological data suggest that insomnia may be a modifiable risk factor for cardiovascular diseases. A randomized controlled trial in a sample of insomnia patients without cardiovascular disease was conducted to investigate the effects of insomnia treatment on early markers of cardiovascular diseases assessed by 24-hr ambulatory blood pressure, heart rate and heart rate variability monitoring, and morning fasting blood samples. Forty-six patients with insomnia disorder were randomized to cognitive behavioural therapy for insomnia (CBT-I; n=23) or a waitlist control condition (n=23). Contrary to the hypothesis, intention-to-treat analyses did not show any significant treatment effects on early markers of cardiovascular disease (d=0.0-0.6) despite successful insomnia treatment (d=1.3). Potential methodological and conceptual reasons for these negative findings are discussed. Future studies might include larger sample sizes that are at risk of cardiovascular diseases and focus on other cardiovascular markers.

Susceptibility to Hyperglycemia in Rats With Stress-Induced Depressive-Like Behavior: Involvement of IL-6 Mediated Glucose Homeostasis Signaling.

Depression is a common psychiatric disorder comorbid with diabetes and may lead to high morbidity, disability, and mortality. However, the underlying mechanism behind their association remains unknown. Cytokine-mediated inflammation in brain may play important roles in the pathogenesis of depression and insulin resistance. In the present study, we subjected the rats to chronic unpredictable mild stress (CUMS) for 3 to 8 weeks. The tests to ascertain depression-like behaviors including open field test (OFT) and forced swimming test (FST) were performed, and levels of morning fasting blood glucose, triglyceride (TG), total cholesterol (CHOL), high density lipoprotein cholesterol (HDL-C), and low density lipoprotein cholesterol (LDL-C), body weight, food intake, histopathological examinations of liver, adipose tissues and hypothalamus, hypothalamic GLUT4 as well as the IL-6-mediated glucose homeostasis signaling pathway were measured. The results showed that CUMS exposure resulted in the depression-like behavior at various time points in rats. Moreover, the rats exhibited increased peripheral glucose levels, impaired hepatocytes and hippocampal neurons, and decreased hypothalamic GLUT4 levels after 6 weeks of CUMS exposure. Meanwhile, activated IL-6 but suppressed IL-6-mediated glucose homeostasis signaling was observed in the hypothalamus. Markers of lipid metabolism including TG, CHOL, HDL-C and LDL-C were dysregulated, and body weight and food intake were decreased in the CUMS-exposed rats. Our results show that depressed rats induced by 6-week CUMS stimulation display susceptibility to hyperglycemia, which is associated with IL-6-mediated inhibition of glucose homeostasis signaling in the hypothalamus.

Association between puberty with thyroid morphology and function in women

Objective: To explore the effects of different puberty development stages on thyroid morphology and function in women. Methods: From October to November 2017, a multi-stage cluster sampling method was used to select one junior high school in Minhang district of Shanghai, Haimen city of Jiangsu province, Yuhuan city of Zhejiang province and Deqing county of Zhejiang province respectively. A total of 491 girls in the first grade in 4 schools were included in the study. The subjects were examined with thyroid B-ultrasound and physical examination, and their morning random urine samples and fasting blood samples were collected to detect urinary iodine and thyroid function indexes. Puberty Development Self-rating Scale (PDS) was used to evaluate the stages of puberty; multiple linear regression models and logistic regression models were used to investigate the effects of different puberty stages on thyroid morphology and function. Results: There were differences in thyroid status among women at different stages of puberty. Thyroid volume, the rate of nodules and the level of FT4 were lowest in prepubertal period, followed by pubertal period and postpubertal period (P<0.05). TT3 and FT3 levels were highest in prepubertal period, followed by pubertal period and postpubertal period (P<0.001), and there was an opposite trend on the abnormal rate. TSH and TT4 levels were not affected by the stage of puberty (P>0.05). Multiple linear regression analysis and multivariate logistic regression analysis showed consistent results. There was a negative correlation between puberty development and TT3 and FT3 levels. For each 1 point increase in PDS, TT3 and FT3 levels decreased by 0.067 nmol/L and 0.170 nmol/L in Model 1, respectively, and decreased by 0.065 nmol/L and 0.162 nmol/L in Model 2, respectively. Compared with the prepubertal period, the TT3 and FT3 levels were lower in postpubertal period (Model 1: OR=0.337, 95%CI: 0.173-0.658; OR=0.283, 95%CI: 0.144-0.557; Model 2: OR=0.306, 95%CI: 0.155-0.605; OR=0.263, 95%CI: 0.132-0.524). Conclusions: The process of puberty is related to the thyroid status in women. The better matured during the puberty, the larger volume the thyroid was, more likely the thyroid nodules appeared, and the levels of TT3 and FT3 was much lower.

Does Exercise Timing Affect 24-Hour Glucose Concentrations in Adults With Type 2 Diabetes? A Follow Up to the Exercise-Physical Activity and Diabetes Glucose Monitoring Study

ObjectivesIt is well known that exercise can improve the glycemic profile in individuals with type 2 diabetes (T2D). However, the optimal timing of exercise is often debated. Our aim in this study was to compare the effects of exercise performed at different times of the day and different timing in relation to meals on 24-hour glucose profiles in people with T2D. MethodsFourteen individuals with T2D were recruited and wore continuous glucose monitors for 12 days. During the 12 days, participants completed 4 conditions according to a randomized, crossover design: i) morning (fasting) exercise (MorEx), ii) afternoon exercise (AftEx), iii) evening exercise (EveEx) and iv) seated control. Exercise consisted of 50 minutes of walking at 5.0 km/h. ResultsEight men and 6 women (age, 65±9.0 years; T2D duration, 10.5±6.8 years; mean glycated hemoglobin, 6.7±0.6%) were included in the analysis. Mean 24-hour continuously monitored glucose was 7.4±0.7 mmol/L, 7.3±0.7 mmol/L, 7.5±0.8 mmol/L and 7.5±0.7 mmol/L in the MorEx, AftEx, EveEx and control conditions, respectively, with no significant differences among the 4 conditions (p=0.55). MorEx had a lower respiratory exchange ratio compared with AftEx and EveEx (p<0.01). The decrease in glucose during exercise was less pronounced for MorEx compared with AftEx (p<0.05). ConclusionsFifty minutes of walking at 3 different times of day and at different timing in relation to meals did not lower 24-hour glucose concentrations in people with T2D. The reasons why exercise was not effective at lowering glucose remain unclear.

1088-P: Postprandial Dynamics of Glucagon Secretion in Type 2 Diabetic Patients: Changes Associated with Short-Term Improvements in Glycemic Control

Objective: Type 2 diabetic patients were examined for their postprandial dynamics of glucagon secretion as well as for changes in these dynamics associated with short-term improvements in their glycemic control. Methods: A total of 75 type 2 diabetic patients admitted for glycemic control who were not receiving incretin-related drugs (I) and SGLT2 inhibitors (S) at admission, 5 type 1 diabetic patients, 5 nondiabetic patients were subjected to meal tolerance tests (MTTs) during early morning fasting hours at admission. Blood samples were drawn from these patients preprandially, and 30, 60, and 120 minutes postprandially to measure their glucose, C-peptide and glucagon (Mercodia) values. Of the type 2 diabetic patients, those who improved glycemic control without both I and S (n = 10), were examined for changes in the postprandial dynamics of glucagon associated with improvements in glycemic control. Results: The AUC C-peptide values was shown to be the lowest in type 1 diabetic patients, followed by type 2 diabetic patients and nondiabetic patients, and with AUC-glucose values and AUC-glucagon values were shown to be the highest in type 1 diabetic patients, followed by type 2 diabetic patients and nondiabetic patients. Of the type 2 diabetic patients, those with BMI ≥ 25 kg/m2 and BMI &amp;lt; 25 kg/m2 were not significantly different in their AUC glucose, while those with BMI ≥ 25 kg/m2 had significantly larger AUC C-peptide and AUC glucagon values than those with BMI &amp;lt; 25 kg/m2. MTTs performed after improving glycemic control showed significantly smaller AUC glucose, significantly elevated AUC C-peptide, and significantly smaller AUC glucagon values in those improving glycemic control without both I and S after admission. Conclusions: Study results are in agreement with the conventional finding that decreased α-cell insulin action associated with decreased insulin secretion or insulin resistance leads to glucagon over-secretion secondarily. Disclosure R. Kanai: None. Y. Mori: None. R. Nishimura: Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc. Speaker’s Bureau; Self; Abbott, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly Japan K.K., Medtronic, Merck &amp; Co., Inc., Novo Nordisk Inc., Sanofi K.K., Takeda Pharmaceutical Company Limited.

2222-PUB: Differences In Clinical Background between Patients with and without Increased Glucagon Secretion while on SGLT2 Inhibitors: A Comparison of Canagliflozin and Other SGLT2 Inhibitors

Objective: This study was conducted to characterize differences in clinical background between patients with and without increased glucagon secretion while on SGLT2 inhibitors (S). Methods: Of the 75 type 2 diabetic patients admitted for glycemic control who were not receiving incretin-related drugs nor S at admission, 22 patients received S but no incretin-related drugs after admission and were subjected to meal tolerance tests (MTTs) during early morning fasting hours at admission and after improving glycemic control. Blood samples were drawn from these patients preprandially and 30, 60, and 120 minutes postprandially to measure their glucose, C-peptide, and glucagon (Mercodia) values. First, based on changes in glucagon secretion observed in MTTs, they were divided into those with increased AUC glucagon (n = 13) and those without (n = 9) and compared for changes in MTT parameters. Then, they were also divided canagliflozin (Cana) group (n = 12) and other S (non-Cana) group (n = 10) and compared for changes in MTT parameters. Results: Although those without increased AUC glucagon showed a significant increase in ΔCPR/Δglucose 0-30 min after improving glycemic control, those with increased AUC glucagon did not. Increased Δ CPR/Δ glucose 0-30 min values were noted in 5 of 13 of those with increased AUC glucagon but in 9/9 of those without, suggesting that those without increased AUC glucagon were more likely to be associated with increased Δ CPR/Δ glucose 0-30 min values. On the other hand, no significant difference was seen in changes in AUC glucagon or in the proportion of patients with increased AUC glucagon between the Cana and non-Cana groups. Conclusions: Study results suggest that differences in the recovery of insulin secretion between patients may affect glucagon secretion to a greater extent than differences between S with or without SGLT1-inhibitory properties. Disclosure M. Ishiguro: None. Y. Mori: None. R. Nishimura: Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc. Speaker’s Bureau; Self; Abbott, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly Japan K.K., Medtronic, Merck &amp; Co., Inc., Novo Nordisk Inc., Sanofi K.K., Takeda Pharmaceutical Company Limited.

Plasma glucocorticogenic activity, race/ethnicity and alcohol intake among San Francisco Bay Area women.

Racial and ethnic minorities are at higher risk for a variety of diseases. While sociodemographic and lifestyle factors contribute to racial/ethnic health disparities, the biological processes underlying these associations remain poorly understood. Stress and its biological consequences through the glucocorticoid receptor (GR) have been hypothesized to mediate adverse disease outcomes. In fasting morning samples of 503 control women from the San Francisco Bay Area Breast Cancer Study, we used a sensitive Chemical-Activated LUciferase gene eXpression (CALUX) assay to examine the association of sociodemographic and lifestyle factors with plasma glucocorticogenic (G) activity in three racial/ethnic groups. The G activity is a sensitive measure that reflects biological activity of total plasma glucocorticoids including cortisol and glucocorticoid-like compounds. Associations between G activity and sociodemographic and lifestyle factors were examined using multivariable linear regression models. Latina and non-Latina Black (NLB) women had 9% (P = 0.053) and 14% (P = 0.008) lower morning G activity than non-Latina White (NLW) women, respectively. Additionally, we replicated a previously reported association between G activity and alcohol intake (women who drank >10gms had 19% higher G activity than non-drinkers, P = 0.004) in Latina and NLB women. Further research should assess the association between G activity and health outcomes in a prospective cohort so as to characterize the relationship between total plasma G activity in pre-disease state and disease outcomes across different racial/ethnic populations.

SO091URINE-TO-PLASMA UREA RATIO, AS SURROGATE MARKER FOR URINE CONCENTRATING CAPACITY, IS ASSOCIATED WITH DISEASE PROGRESSION IN ADPKD

Abstract Introduction Predicting disease progression in autosomal dominant polycystic kidney disease (ADPKD) patients poses a challenge, especially in early stage disease when renal function is not yet affected. The ongoing formation and growth of cysts causes the urine concentrating capacity to decrease from early on in the disease. We therefore hypothesized that the easy and inexpensive to measure urine-to-plasma urea ratio (UPU ratio), which is assumed to be surrogate for maximal urine concentrating capacity, can be used as marker to predict disease progression in ADPKD. Methods The UPU ratio was calculated by dividing urea concentration in a fasting morning spot urine sample by plasma urea concentration adjusted for plasma creatinine concentration. First, we validated the UPU ratio in 30 ADPKD patients who underwent a prolonged water deprivation test to measure the maximal urine concentrating capacity. Thereafter, the association of the UPU ratio with renal outcome was evaluated in 583 ADPKD patients participating in the DIPAK observational cohort (inclusion criteria: age&amp;gt;18 years, eGFR &amp;gt;15 mL/min/1.73m2, no concomitant diseases affecting eGFR, without V2 receptor antagonist prescription). Kidney function was assessed as eGFR by the creatinine based CKD-EPI formula, height adjusted total kidney volume (htTKV) by MRI and copeptin (surrogate for vasopressin) by ELISA. Results In the water deprivation test participants (n=30), the UPU ratio was strongly correlated with maximal urine concentrating capacity (R = 0.67, p&amp;lt;0.001). This association remained significant after correcting for sex, age, htTKV and eGFR (st. β = 0.53, p = 0.007). In these subjects maximal urine concentrating capacity as well as UPU ratio were associated with the rate of eGFR decline during a median follow-up of 6.3 yr (12 eGFR assessments per patient) assessed using linear mixed modeling, also when corrected for sex, baseline age and eGFR (β = 0.009, p = 0.04, and β = 5.56, p&amp;lt;0.001, resp.). We subsequently corroborated in the larger DIPAK observational cohort (n=583, 58% female, mean age 47 yr median eGFR 60 mL/min/1.73m2 and htTKV 898 ml/m), that the UPU ratio was significantly associated with rate of eGFR decline during a median follow-up of 4.0 yr (6 eGFR assessments per patient): β = 0.23, p = 0.005. This association remained significant when corrected for sex, baseline age and eGFR (β = 0.32, p&amp;lt;0.001) and even when additionally corrected for Mayo class, PDK mutation and copeptin (β = 0.40, p &amp;lt;0.001). Stepwise backward multivariate regression analysis resulted in a final model including the UPU ratio, PKD mutation, Mayo Class and copeptin. Cox survival analysis showed that a lower baseline UPU ratio (indicating less urine concentrating capacity) was significantly associated with a higher risk to develop the combined renal endpoint of incidence of start of kidney replacement therapy, eGFR &amp;lt;15 mL/min/1.73m2 or eGFR decrease &amp;gt;40% during follow-up (adjusted Hazard Ratio per SD = 1.39, p = 0.007). Limiting the aforementioned analyses to the subgroup of patients with relative early stage disease (n=122, age &amp;lt;40 yr and eGFR &amp;gt;60 mL/min/1.73m2) rendered essentially similar results, with an adjusted β for UPU ratio in the final model of 0.33 (p = 0.04). In this subgroup with a limited number of events (n=10), Cox survival analysis did not reach formal significance (adjusted HR per SD: 2.67, p = 0.055). Conclusion The UPU ratio, which is calculated from routine laboratory measurements, predicts renal prognosis in ADPKD in addition to other, more laborious to measure and expensive risk markers. Notably, this marker of urine concentrating capacity also shows promise in early-stage disease.