Dopamine receptor agonists mechanism of actions on glucose lowering and their connections with prolactin actions.

Robust experiment evidence suggests that prolactin can enhance beta-cell proliferation and increase insulin secretion and sensitivity. Apart from acting as an endocrine hormone, it also function as an adipokine and act on adipocytes to modulate adipogenesis, lipid metabolism and inflammation. Several cross-sectional epidemiologic studies consistently showed that circulating prolactin levels positive correlated with increased insulin sensitivity, lower glucose and lipid levels, and lower prevalence of T2D and metabolic syndrome. Bromocriptine, a dopamine receptor agonist used to treat prolactinoma, is approved by Food and Drug Administration for treatment in type 2 diabetes mellitus since 2009. Prolactin lowering suppress insulin secretion and decrease insulin sensitivity, therefore dopamine receptor agonists which act at the pituitary to lower serum prolactin levels are expected to impair glucose tolerance. Making it more complicating, studies exploring the glucose-lowering mechanism of bromocriptine and cabergoline have resulted in contradictory results; while some demonstrated actions independently on prolactin status, others showed glucose lowering partly explained by prolactin level. Previous studies showed that a moderate increase in central intraventricular prolactin levels stimulates hypothalamic dopamine with a decreased serum prolactin level and improved glucose metabolism. Additionally, sharp wave-ripples from the hippocampus modulates peripheral glucose level within 10 minutes, providing evidence for a mechanistic link between hypothalamus and blood glucose control. Central insulin in the mesolimbic system have been shown to suppress dopamine levels thus comprising a feedback control loop. Central dopamine and prolactin levels plays a key role in the glucose homeostasis control, and their dysregulation could lead to the pathognomonic central insulin resistance depicted in the "ominous octet". This review aims to provide an in-depth discussion on the glucose-lowering mechanism of dopamine receptor agonists and on the diverse prolactin and dopamine actions on metabolism targets.

A Randomized Controlled Trial of R-Form Verapamil Added to Ongoing Metformin Therapy in Patients with Type 2 Diabetes.

CONTEXT: There is a medical need for effective insulin-independent antidiabetic drugs that can promote pancreatic ß-cell function and have a low risk of hypoglycemia in type 2 diabetes mellitus (T2DM) patients. R-form verapamil (R-Vera), which is able to enhance the survival of ß-cells and has higher cardiovascular safety margin compared with racemic verapamil, was developed as a novel approach for T2DM treatment. OBJECTIVE: This randomized, double-blind, placebo-controlled clinical trial was designed to evaluate the efficacy and safety of 3 dosages of R-Vera added to ongoing metformin therapy in T2DM patients who had inadequate glycemic control on metformin alone. METHODS: Participants were randomly assigned in an equal ratio to receive R-Vera 450, 300, or 150 mg per day, or matching placebo, in combination with metformin. The primary endpoint was change in hemoglobin A1c (HbA1c) after 12 weeks of treatment. RESULTS: A total of 184 eligible participants were randomized to receive either R-Vera or placebo plus metformin. At week 12, significant reductions in HbA1c were observed for R-Vera 300 mg/day (-0.36, P = 0.0373) and 450 mg/day (-0.45, P = 0.0098) compared with placebo. The reduction in HbA1c correlated with decreasing fasting plasma glucose levels and improved HOMA2-ß score. Treatment with R-Vera was well tolerated with no hypoglycemic episodes occurring during the trial. CONCLUSION: Addition of R-Vera twice daily to ongoing metformin therapy significantly improved glycemic control in T2DM patients. The favorable efficacy and safety profile of R-Vera 300 mg/day can be considered as the appropriate dose for clinical practice.

Using a simple spectrophotometer to analyze cypress hydrolat composition.

The Pure Dew (Cypress Hydrolat), which could be extracted from the waste material after the extracting essential oil from Taiwan cypress, has a good bactericidal effect. However, due to the high cost on quality control and concentration measurement of the Pure Dew, its application was restricted. This research tries to find suitable spectral frequencies through which the absorbance detected by the spectrometer could be used as the index of the pure dew concentration. This study used Gas Chromatography-Mass Spectrophotometer (GC-MS) to analyze the composition of Taiwan cypress hydrolat. After obtaining the composition, the raw liquor of cypress hydrolat was diluted to 100, 50, 25 and 0% v/v with pure water. The test samples were then tested by a simple spectrophotometer. After the spectrographic detection of absorbance using a simple spectrophotometer, it is confirmed that the spectrum of wavelength between 205-350 nm is the most representative. The absorptance and the pure dew concentration was roughly in linear relation which suggested that a simple spectrophotometer can be used to develop a low-cost and high.

Nocturia in Women With Type 2 Diabetes Mellitus: A Cross-sectional, Correlation Study.

PURPOSE: The first aim of this study was to compare nighttime voiding frequency (nocturia), serum hemoglobin A1c level, peripheral neuropathy score, and global sleep quality score in younger (>40 to <65 years) versus older (≥65 years) women with type 2 diabetes mellitus (DM). Additional aims were to identify factors associated with clinically relevant nocturia (≥2 episodes/night) and to analyze relationships between nocturia frequency, glycemic control, peripheral neuropathy, and sleep quality in these women. DESIGN: Cross-sectional study. SETTING AND SUBJECTS: Participants were 118 women older than 40 years and with type 2 DM. Their mean age was 65.25 (SD = 9.66) years; the mean duration since diagnosis of type 2 DM was 10.96 (SD = 7.66) years. The study setting was 2 metabolism and endocrinology outpatient departments located in Taipei City and Taoyuan, Taiwan. METHODS: Data were collected using a questionnaire that queried sociodemographic information, lower urinary tract symptoms, and sleep quality. We also assessed peripheral neuropathy and lower extremity edema and obtained pertinent information from participants' medical records. Independent t tests, multivariate logistic regression analyses, Spearman's rank correlation coefficients, and one-way analysis of variance were used to address the 3 study aims. RESULTS: Analyses found that older women (aged ≥65 years) had a significantly higher nighttime voiding frequency, a higher peripheral neuropathy score, and a higher sleep quality score than younger (>40 to <65 years) women. Multivariate logistic regression analyses identified 4 factors associated with clinically relevant nocturia advanced age, elevated hemoglobin A1c level, suspected peripheral neuropathy, and lower extremity edema. Significant correlation coefficients were found between nighttime voiding frequency and serum hemoglobin A1c levels, peripheral neuropathy scores, and sleep quality scores. Analyses also found that women with a greater nocturia frequency had higher hemoglobin A1c levels, peripheral neuropathy scores, and sleep quality scores. CONCLUSIONS: Healthcare professionals should screen for nocturia in women with type 2 DM and provide appropriate management for those experiencing nocturia.

Fast honey classification using infrared spectrum and machine learning.

Honey has been one previous natural food in human history. However, as the supply cannot satisfy the market demand, many incidents of adulterated and fraudulent honey have been reported. In Taiwan, some common adulterated honey and fraudulent honey incidents include (1) mixing honey with fructose, (2) importing cheap honey abroad but labeling them as domestic honey, and (3) labeling cheaper honey (for example, nectar and lychee honey) as high-price honey (for example, longan honey). It is very difficult for consumers to tell the genuineness of the labeling of honey. To protect consumers and honest honey producers, we aim at exploring and developing an efficient and convenient technology that can effectively classify honey. We analyze the infrared spectra of honey samples and apply machine learning technologies to classify honey. The experimental results confirm that this technology can effectively distinguish several main honey types in Taiwan. This technology has the advantages of non-destruction, immediacy, and low manpower. It can serve as an effective tool to fast screen honey products.

Are Older Adults without a Healthy Diet Less Physically Active and More Sedentary?

Few studies on older populations consider several energy balance-related behaviors together. This cross-sectional study compared subjectively and objectively measured physical activity (PA) and sedentary behavior (SB) patterns between older adults with and without a healthy diet. We recruited 127 community-dwelling older Taiwanese adults (69.9 ± 5.0 years); data were collected during April and September 2018. Objectively measured total PA, moderate-to-vigorous PA, light PA, step count, total sedentary time, duration of sedentary bouts, number of sedentary bouts, and number of sedentary breaks were assessed using activity monitors. Subjectively measured PA and SB were measured using the International Physical Activity Questionnaire and Sedentary Behavior Questionnaire for Older Adults. Chi-square tests and independent sample t-tests were performed. For subjective measures, older adults without a healthy diet spent significantly less total leisure time on PA and more leisure sitting time than those with a healthy diet. For objective measures, older adults without a healthy diet spent less time on light PA and had a higher total sedentary time, duration of sedentary bouts, times of sedentary bouts, and times of sedentary breaks than those with a healthy diet. Regardless of the use of objective or subjective measurements, older adults without a healthy diet engaged in a more inactive and sedentary lifestyle. These findings have implications for health promotion practitioners in designing tailored interventions.

ß-human chorionic gonadotropin-secreting intracranial germ-cell tumor associated with high testosterone in an adult man: A case report.

A 38-year-old male patient presented with general weakness, polydipsia and a body weight loss of 10 kg in two years. Hypopituitarism with central hypothyroidism and central adrenal insufficiency were noted at Taipei City Hospital (Taipei, Taiwan). However, hypogonadotropic hypergonadism was also observed. The patient was diagnosed with an intracranial ß-human chorionic gonadotropin (ß-hCG) secreting germ-cell tumor, and brain magnetic resonance imaging revealed that the tumor involved the pineal gland, stalk, posterior pituitary gland, right basal ganglion, hypothalamus, corpus callosum and posterior hippocampus. The cerebrospinal fluid (CSF) ß-hCG level was 1936 IU/l, while the α-fetoprotein (AFP) level was <0.24 ng/ml. The serum AFP level of the patient was 3.28 ng/ml, and the ß-hCG level was 178 IU/l with a CSF:serum ß-hCG ratio >2:1. The patient was successfully treated with chemotherapy and radiotherapy, as demonstrated by a marked decrease in size of the tumor and in the serum ß-hCG levels. Intracranial ß-hCG secreting germ-cell tumors are rare in adults and manifest differently compared with patients of early pubertal age. In contrast with the precocious puberty frequently observed in young patients, the diagnosis of adult patients is often delayed and the symptoms are associated with tumor size and location. The present case report described an adult male with an intracranial ß-hCG secreting GCT, demonstrating hypopituitarism and asymptomatic hyperandrogenemia, and reviews and discusses the literature relevant to the case.

Differential microRNA Profiles Predict Diabetic Nephropathy Progression in Taiwan.

OBJECTIVES: Diabetic nephropathy (DN) is a major leading cause of kidney failure. Recent studies showed that serological microRNAs (miRs) could be utilized as biomarkers to identify disease pathogenesis; the DN-related miRs, however, remained to be explored. METHODS: A prospective case-control study was conducted. The clinical significance of five potential miRs (miR-21, miR-29a, miR-29b, miR-29c and miR192) in type 2 Diabetes Mellitus (T2DM) patients who have existing diabetic retinopathy with differential Albumin:Creatinine Ratio (ACR) and estimated Glomerular Filtration Rate (eGFR) was performed using quantitative RT-PCR analysis. The subjects with diabetic retinopathy enrolled in Taipei City Hospital, Taiwan, were classified into groups of normal albuminuria (ACR<30mg/g; N=12); microalbuminuria (30mg/g300mg/g; N=21) as well as 18 low-eGFR (eGFR<60ml/min) and 32 high-eGFR (eGFR>60ml/min). The level of serum miRs was statistically correlated with age, Glucose AC, ACR, eGFR and DN progression. RESULTS: The levels of miR-21, miR-29a and miR-192 were significantly enriched in the overt proteinuria group compared with microalbuminuria and/or overt proteinuria groups. It was shown that only miR-21 level was significantly up-regulated in low-eGFR group compared with high-eGFR patients. Interestingly, Pearson's correlation coefficient analysis demonstrated that DN progressors showed significantly greater levels of miR-21, miR-29a, miR-29b and miR-29c in comparison with non-progressors implying the clinical potential of DN associated miRs in monitoring and preventing disease advancement. CONCLUSION: Our findings showed that miR-21, miR-29a/b/c and miR-192 could reflect DN pathogenesis and serve as biomarkers during DN progression.

Association of thyroid-stimulating hormone and cardiovascular risk factors.

Thyroid hormone plays an important role in regulating the lipid and glucose metabolism. Previously, much attention has been drawn to define the pathophysiological relationship between thyroid dysfunction and the incidence of cardiovascular diseases (CVDs). While the conditions of overt hypothyroidism and subclinical hypothyroidism were both emphasized, the association between CVD risks and the deregulated circulating thyroid-stimulating hormone (TSH) level remains to be elucidated. Nevertheless, multiple TSH-mediated physiological adaptations, including alteration of the serum lipids, body mass index, blood pressure and insulin sensitivity, have led to the difficulty of clearly examining the association between the TSH level and CVD prevalence. The current review aims to 1) summarize the evidence for the role of thyroid dysfunction and TSH abnormality in CVD pathogenesis and 2) explore the possible underlying molecular mechanisms of TSH-mediated cardiovascular pathology in hopes of providing better therapeutic strategies for the patients with deregulated TSH.

Circulating microRNA as a diagnostic marker in populations with type 2 diabetes mellitus and diabetic complications.

Diabetes mellitus (DM) is a global health care issue resulting from hyperglycemia-mediated life-threatening complications. Although the use of glucose-lowering agents is routinely practiced, high dependence on medication leads to poor quality of life for DM patients. While it is still not feasible to precisely determine the critical timing when DM is truly established, perhaps the best way to reduce DM-associated mortality is to prevent it. To this end, an exploration of prognostic molecules sensitive enough to detect early physiological alteration at the initiating stage would be required. Recently discovered small noncoding molecules, microRNAs (miRs), in body fluid seem promising to be utilized as a biomarker to monitor DM initiation and progression, as it is believed that expression of circulating miRs reflects disease pathology. Current DM-related miRs were often referred to miRs differentially expressed in insulin target organs (liver, muscle, and adipose tissues) or circulating blood (peripheral blood) in diabetic patients compared to their control counterparts, although these miRs could merely be resultant nucleotides from DM-induced organ impairment instead of the indicators of onset/progression of DM. In the current review, studies showing circulating miRs associated with type 2 DM and its complications are summarized, and future scope of using miRs as biomarkers for disease prognosis/diagnosis is also emphasized.

The regulation and function of the NUAK family.

AMP-activated protein kinase (AMPK) is a critical regulator of cellular and whole-body energy homeostasis. Twelve AMPK-related kinases (ARKs; BRSK1, BRSK2, NUAK1, NUAK2, QIK, QSK, SIK, MARK1, MARK2, MARK3, MARK4, and MELK) have been identified recently. These kinases show a similar structural organization, including an N-terminal catalytic domain, followed by a ubiquitin-associated domain and a C-terminal spacer sequence, which in some cases also contains a kinase-associated domain 1. Eleven of the ARKs are phosphorylated and activated by the master upstream kinase liver kinase B1. However, most of these ARKs are largely unknown, and the NUAK family seems to have different regulations and functions. This review contains a brief discussion of the NUAK family including the specific characteristics of NUAK1 and NUAK2.

Two RFID-based solutions to enhance inpatient medication safety.

Owing to the low cost and convenience of identifying an object without physical contact, Radio Frequency Identification (RFID) systems provide innovative, promising and efficient applications in many domains. An RFID grouping protocol is a protocol that allows an off-line verifier to collect and verify the evidence of two or more tags simultaneously present. Recently, Huang and Ku (J. Med. Syst, 2009) proposed an efficient grouping protocol to enhance medication safety for inpatients based on low-cost tags. However, the Huang-Ku scheme is not secure; an attacker can easily make up fake grouping records to cheat the verifier. This weakness would seriously endanger the safety of inpatient medication safety. This paper will show the weaknesses, and then propose two RFID-based solutions to enhance medication safety for two different scenarios. The proposed schemes are practical, secure and efficient for medication applications.