Comment on Martínez-Delgado et al. Using Absorption Models for Insulin and Carbohydrates and Deep Leaning to Improve Glucose Level Predictions. Sensors 2021, 21, 5273.

The paper "Using Absorption Models for Insulin and Carbohydrates and Deep Leaning to Improve Glucose Level Predictions" (Sensors2021, 21, 5273) proposes a novel approach to predicting blood glucose levels for people with type 1 diabetes mellitus (T1DM). By building exponential models from raw carbohydrate and insulin data to simulate the absorption in the body, the authors reported a reduction in their model's root-mean-square error (RMSE) from 15.5 mg/dL (raw) to 9.2 mg/dL (exponential) when predicting blood glucose levels one hour into the future. In this comment, we demonstrate that the experimental techniques used in that paper are flawed, which invalidates its results and conclusions. Specifically, after reviewing the authors' code, we found that the model validation scheme was malformed, namely, the training and test data from the same time intervals were mixed. This means that the reported RMSE numbers in the referenced paper did not accurately measure the predictive capabilities of the approaches that were presented. We repaired the measurement technique by appropriately isolating the training and test data, and we discovered that their models actually performed dramatically worse than was reported in the paper. In fact, the models presented in the that paper do not appear to perform any better than a naive model that predicts future glucose levels to be the same as the current ones.

Pichia pastoris Mediated Digestion of Water-Soluble Polysaccharides from Cress Seed Mucilage Produces Potent Antidiabetic Oligosaccharides.

Diabetes mellitus is a heterogeneous metabolic disorder that poses significant health and economic challenges across the globe. Polysaccharides, found abundantly in edible plants, hold promise for managing diabetes by reducing blood glucose levels (BGL) and insulin resistance. However, most of these polysaccharides cannot be digested or absorbed directly by the human body. Here we report the production of antidiabetic oligosaccharides from cress seed mucilage polysaccharides using yeast fermentation. The water-soluble polysaccharides extracted from cress seed mucilage were precipitated using 75% ethanol and fermented with Pichia pastoris for different time intervals. The digested saccharides were fractionated through gel permeation chromatography using a Bio Gel P-10 column. Structural analysis of the oligosaccharide fractions revealed the presence of galacturonic acid, rhamnose, glucuronic acid, glucose and arabinose. Oligosaccharide fractions exhibited the potential to inhibit α-amylase and α-glucosidase enzymes in a dose-dependent manner in vitro. The fraction DF73 exhibited strong inhibitory activity against α-amylase with IC50 values of 38.2 ± 1.12 µg/mL, compared to the positive control, acarbose, having an IC50 value of 29.18 ± 1.76 µg/mL. Similarly, DF72 and DF73 showed the highest inhibition of α-glucosidase, with IC50 values of 9.26 ± 2.68 and 50.47 ± 5.18 µg/mL, respectively. In in vivo assays in streptozotocin (STZ)-induced diabetic mice, these oligosaccharides significantly reduced BGL and improved lipid profiles compared to the reference drug metformin. Histopathological observations of mouse livers indicated the cytoprotective effects of these sugars. Taken together, our results suggest that oligosaccharides produced through microbial digestion of polysaccharides extracted from cress seed mucilage have the potential to reduce blood glucose levels, possibly through inhibition of carbohydrate-digesting enzymes and regulation of the various signaling pathways.

Useful of proximal gastrectomy with double-tract reconstruction in preventing glucose spikes.

BACKGROUND: Volatile glucose levels after gastrectomy induce dumping syndrome, which adversely affects patient quality of life. This study aimed to evaluate the glycemic variability of proximal gastrectomy with double-tract reconstruction (PGDTR) as a function-preserving procedure. METHODS: This study used a continuous glucose monitoring (CGM) system to record glycemic profiles of patients who underwent PGDTR or total gastrectomy (TG) and compared them. Moreover, this study evaluated postgastrectomy syndrome, including dumping symptoms, between the PGDTR and TG groups using the 37-item Postgastrectomy Syndrome Assessment Scale (PGSAS-37) questionnaire. RESULTS: Of note, 44 patients underwent PGDTR, and 42 patients underwent TG, which included more advanced cases. CGM results showed that the SD, relative SD, and maximum drop in glucose level between 30 min and 2 h after a meal were smaller in the PGDTR group than in the TG group (14.81 vs 22.40 mg/dL [P < .001], 0.14 vs 0.20 mg/dL [P < .001], and 42.06 vs 117.67 mg/dL [P < .001], respectively). For nocturnal glucose levels, SD and percentage time below the range were smaller in the PGDTR group than in the TG group (11.76 vs 15.16 mg/dL [P = .005] and 11.25% vs 35.27% [P < .001]). The PGDTR group generally performed better than the TG group on all the PGSAS-37 questionnaire items. Patients in the PGDTR group without food inflow into the remnant stomach showed similar CGM results as those in the TG group but with stronger dumping symptoms. CONCLUSION: Food inflow into the remnant stomach is essential for PGDTR to be a function-preserving procedure as it leads to the control of dumping symptoms and lower glucose level spikes.

Quantification of the Anti-diabetic Effect of Allium cepa.

BACKGROUND: Allium cepa, or onion, boosts numerous health benefits, including anti-diabetic effects. Its rich array of antioxidants and sulfur compounds not only aids heart health by lowering cholesterol and blood pressure but also exhibits anti-inflammatory properties. Onion's antibacterial and antiviral properties help combat infections, while its compounds like quercetin show promise in cancer prevention. Additionally, Allium cepa supports respiratory health by relieving coughs and colds and aids digestion with its prebiotic properties. Incorporating onions into a balanced diet can enhance overall well-being, including managing blood sugar levels in individuals with diabetes. AIM AND OBJECTIVE: This study aims to determine if the ethanolic extract from the dried peel of Allium cepa holds potential as an anti-diabetic agent, with a focus on its ability to manage diabetes and reduce blood sugar levels. METHODOLOGY: To prepare the ethanolic extract from dried onion peel, the peel was finely ground and soaked in ethanol. The mixture was then agitated and filtered to separate the liquid extract. Finally, the filtrate was concentrated using methods such as rotary evaporation or vacuum distillation to obtain a concentrated extract for further analysis like alpha-amylase inhibition assay and alpha-glucosidase inhibition assay. RESULTS: The ethanolic extracts derived from dried onion peel demonstrate inhibition of alpha-glucosidase, leading to reduced blood glucose levels. Additionally, this inhibition prompts an increase in insulin production. CONCLUSION: The study underscores that the efficacy of the ethanolic extract of dried onion peel increases with concentration. It highlights the presence of beneficial compounds like total phenolics, flavonoids, quercetin, and its derivatives in onion peel, known for their therapeutic roles in cardiovascular health, weight management, diabetes control, cancer prevention, and antimicrobial activity. These findings affirm the hypoglycemic and anti-diabetic properties of Allium cepa's ethanolic leaf extract.

Effect of Ruzu Herbal Bitters on the Liver Function and Lipid Profile Parameters of Alloxan-Induced Diabetic Rats.

Background: Ruzu herbal bitters (RHB) is a polyherbal mixture produced in Nigeria indicated for diabetes and other ailments. The consumers of the product testify of its efficacy, but there are not much scientific information on RHB. The study determined the effect of RHB on the liver function and lipid profile parameters of alloxan-induced diabetic rats. Method: Fifty-four adult albino rats were divided into nine groups of six rats each. Group 1 was the normal control, while groups 2-6 were diabetic. Group 2 was not treated, while groups 3-6 were respectively treated with 5 mg/kg b.w of glibenclamide, 0.14, 0.29, and 0.57 ml/kg b.w of RHB. Groups 7-9 were not diabetic but treated as groups 4-6. Diabetes was induced by intraperitoneal injection of freshly prepared alloxan into adult male albino Wister rats with a single dose of 120 mg/kg body weight. The blood sugar level, weight, liver function, and lipid profile of the rats were tested using standard methods. Result: The results showed a significant (P < 0.05) increase in the blood glucose level and decrease in weight in the diabetic-untreated group compared to the normal group. The liver function and lipid profile tests showed significant (P<0.05) increases in the activities of gamma-glutamyltransferase (GGT), alkaline phosphatase (ALP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST); increases in the levels of total bilirubin, total cholesterol (T.CHOL), triglycerides (TG), very low-density lipoprotein (VLDL) and lowdensity lipoprotein (LDL); decreases in the levels of total protein, albumin and high-density lipoproteins (HDL), in the diabetic-untreated group compared to the normal group. However, treatment of the diabetic rats with different doses of RHB caused the reversal of these effects to near-normal levels in a dose-dependent manner. Conclusions: Our study reveals that RHB has antidiabetic, hepatoprotective, and antihyperlipidemic effects.

Exogenous Ketone Supplement Administration Abrogated Isoflurane-Anesthesia-Induced Increase in Blood Glucose Level in Female WAG/Rij Rats.

It has been demonstrated that isoflurane-induced anesthesia can increase the blood glucose level, leading to hyperglycemia and several adverse effects. The administration of a mix of ketone diester (KE) and medium-chain triglyceride (MCT) oil, named KEMCT, abolished the isoflurane-anesthesia-induced increase in blood glucose level and prolonged the recovery time from isoflurane anesthesia in a male preclinical rodent model, Wistar Albino Glaxo/Rijswijk (WAG/Rij) rats. While most preclinical studies use exclusively male animals, our previous study on blood glucose changes in response to KEMCT administration showed that the results can be sex-dependent. Thus, in this study, we investigated female WAG/Rij rats, whether KEMCT gavage (3 g/kg/day for 7 days) can change the isoflurane (3%)-anesthesia-induced increase in blood glucose level and the recovery time from isoflurane-evoked anesthesia using the righting reflex. Moreover, KEMCT-induced ketosis may enhance both the extracellular level of adenosine and the activity of adenosine A1 receptors (A1Rs). To obtain information on the putative A1R mechanism of action, the effects of an A1R antagonist, DPCPX (1,3-dipropyl-8-cyclopentylxanthine; intraperitoneal/i.p. 0.2 mg/kg), on KEMCT-generated influences were also investigated. Our results show that KEMCT supplementation abolished the isoflurane-anesthesia-induced increase in blood glucose level, and this was abrogated by the co-administration of DPCPX. Nevertheless, KEMCT gavage did not change the recovery time from isoflurane-induced anesthesia. We can conclude that intragastric gavage of exogenous ketone supplements (EKSs), such as KEMCT, can abolish the isoflurane-anesthesia-induced increase in blood glucose level in both sexes likely through A1Rs in WAG/Rij rats, while recovery time was not affected in females, unlike in males. These results suggest that the administration of EKSs as an adjuvant therapy may be effective in mitigating metabolic side effects of isoflurane, such as hyperglycemia, in both sexes.

Temporal trends in the visual impairment burden attributable to high fasting plasma glucose levels: a population-based study.

AIMS: Elevated fasting plasma glucose (FPG) levels have been associated with visual impairment. Recognising global patterns of high FPG level exposure can facilitate the prevention and treatment of related visual impairment. We aimed to assess the trends of the visual impairment burden attributable to high FPG levels globally, regionally, nationally, and by income level. METHODS: We obtained data on the visual impairment burden attributable to high FPG levels from the Global Burden of Disease Study 2019. We evaluated the trends of related disability-adjusted life-years (DALYs) from 1990 to 2019 through joinpoint regression analysis and calculated the annual percentage change (APC) and average APC (AAPC). Countries/territories were categorised into high-, upper-middle-, lower-middle-, and low-income groups based on the 2019 World Bank criteria. RESULTS: The age-standardised rate of DALYs due to visual impairment attributable to high FPG levels significantly increased globally, from 6.75 (95% uncertainty interval [UI], 1.55-15.79) in 1990 to 8.44 per 100,000 population (95% UI, 2.00-19.63) in 2019 (AAPC, 0.79; 95% confidence interval [CI], 0.69-0.89; p < 0.001). The largest increases were observed in high-income (AAPC, 0.73; 95% CI, 0.60-0.85) and lower-middle-income countries/territories (AAPC, 0.68; 95% CI, 0.62-0.73). In 2019, lower-middle-income countries/territories had the highest age-standardised DALY rate (18.94 per 100,000 population; 95% UI, 4.39-43.98), whereas high-income countries/territories had the lowest (2.97 per 100,000 population; 95% UI, 0.75-6.74). CONCLUSIONS: The visual impairment burden associated with elevated FPG levels has increased significantly, necessitating enhanced public health prevention measures, clinical management, and treatment to mitigate adverse outcomes.

Effectiveness of Oral Health Education and Interventions in Improving Oral Health Outcomes in Type II Diabetes Mellitus Patients: A Prospective Study.

Introduction Diabetes mellitus (DM) is a group of metabolic diseases characterized by hyperglycemia resulting from defects in insulin secretion, insulin action, or both. The study aimed to evaluate the effectiveness of oral health education and intervention in improving oral health outcomes in type 2 DM (T2DM) patients. Methods The present study was conducted in the Department of Oral Medicine and Radiology between February 2023 and August 2023 at Saveetha Dental College and Hospitals in Chennai, India. All of the patients in the study had T2DM with oral manifestations. This study enrolled 105 participants, of whom 63 were female and 42 were male. A standard pro forma was given to all the participants, and the findings were recorded. The pro forma comprises different oral manifestations, blood glucose levels, the Decayed, Missing, and Filled Teeth (DMFT) index, and Russell's periodontal index. The results were then statistically analyzed. Results This study of 105 individuals with T2DM (60% females and 40% males) revealed significant oral health challenges: 33% had periodontitis, 20% had gingivitis, 5% had lichenoid reactions, 23% had xerostomia, 11% had halitosis, and 8% had candidiasis, illustrating diabetes' impact on dental health. Following appropriate, tailor-made treatment for individual patients, such as scaling, root planning, oral hygiene education, pharmacotherapy, and post-intervention, the prevalence of complications notably decreased by 61%. A total of 7% of patients had gingivitis, 11% had periodontitis, 12% had xerostomia, 4% had halitosis, 2% had candidiasis, and 1% had lichenoid reactions, respectively. This highlights the importance of regular oral care positively impacting diabetes patients, with 61% experiencing improved oral health and 39% experiencing no improvement. Conclusion This study provides compelling evidence for the effectiveness of oral health education and interventions in improving oral health outcomes in T2DM patients. This approach offers a promising strategy for managing the oral health complications associated with diabetes and improving this population's overall health and well-being.

Prevention of obesity and carbohydrate metabolism disorders in the population at an industrial facility.

Introduction: One of the urgent tasks of modern healthcare is the development of measures aimed at preventing obesity in the able-bodied population, including in the Republic of Kazakhstan, which would reduce economic losses and increase the coefficient of life expectancy in the population. Aim: To identify measures for the early prevention of excess weight, obesity, and carbohydrate metabolism disorders in the able-bodied population at an industrial facility in Kazakhstan. Material and methods: The study involved 662 people (574 men and 88 women) aged 19 to 64 years. The subjects were divided into 2 groups: the main group - persons with obesity (242 people) and the control group - relatively healthy persons (422 people). The diagnosis of obesity was made based on the medical history of a patient, external examination, and physical, laboratory, and instrumental assessment. Results: Three main factors influencing the development of obesity have been identified: a significant level of inactivity; serum glucose; the presence of comorbidities. Other factors (gender and age, smoking) do not have a significant effect on the increase in the body mass index of persons working at an industrial facility. Conclusions: Accordingly, a priority in the prevention of obesity is a healthy lifestyle, involving regular physical activity and a healthy balanced diet.

Safety assessment of crude aqueous methanol extract of Annona senegalensis stem bark: acute and sub-chronic toxicity studies.

Annona senegalensis Pers., (wild custard apple), is a shrub used traditionally to treat respiratory and skin diseases. Previous studies have demonstrated its anti-malaria, anti-snake envenomation and anti-cancer activities. However, its toxicological profile remains limited, particularly in male and female animals. This study aims to evaluate the safety of crude aqueous methanol extract of Annona senegalensis stem bark (AMEAS) through acute and sub-chronic toxicity studies. The stem bark of A. senegalensis was collected, air-dried, pulverized, and extracted using 70% methanol. Phytochemical screening, elemental analysis, and acute toxicity evaluation were carried out on AMEAS. Sub-chronic toxicity study was conducted on Wistar rats of both sexes at different doses administered orally for 28 days. Elemental analysis revealed the presence of heavy metals and essential mineral elements with the highest contents being calcium (59.88%) and potassium (25.39%). Acute toxicity testing showed no mortality up to 5000 mg/kg, suggesting an LD50 greater than 5000 mg/kg. In the sub-chronic toxicity study, no mortality or significant harmful effects were observed. The blood glucose decreased from 13.68 mMol/L at 250 mg/kg to 10.71 mMol/L at 1000 mg/kg, much lower than the distilled water group (17.06 mMol/L). In conclusion, the extract appeared to be well-tolerated, with no obvious adverse effects. AMEAS is rich in Calcium (Ca) and potassium (K). It has been shown to have LD50 greater than 5000 mg/kg and is assumed to be safe. On repeated use, AMEAS may cause hypoglycemia and weight loss which may be useful in managing diabetes and obesity respectively.

Chemerin in Participants with or without Insulin Resistance and Diabetes.

Chemerin is a chemokine/adipokine, regulating inflammation, adipogenesis and energy metabolism whose activity depends on successive proteolytic cleavages at its C-terminus. Chemerin levels and processing are correlated with insulin resistance. We hypothesized that chemerin processing would be higher in individuals with type 2 diabetes (T2D) and in those who are insulin resistant (IR). This hypothesis was tested by characterizing different chemerin forms by specific ELISA in the plasma of 18 participants with T2D and 116 without T2D who also had their insulin resistance measured by steady-state plasma glucose (SSPG) concentration during an insulin suppression test. This approach enabled us to analyze the association of chemerin levels with a direct measure of insulin resistance (SSPG concentration). Participants were divided into groups based on their degree of insulin resistance using SSPG concentration tertiles: insulin sensitive (IS, SSPG ≤ 91 mg/dL), intermediate IR (IM, SSPG 92-199 mg/dL), and IR (SSPG ≥ 200 mg/dL). Levels of different chemerin forms were highest in patients with T2D, second highest in individuals without T2D who were IR, and lowest in persons without T2D who were IM or IS. In the whole group, chemerin levels positively correlated with both degree of insulin resistance (SSPG concentration) and adiposity (BMI). Participants with T2D and those without T2D who were IR had the most proteolytic processing of chemerin, resulting in higher levels of both cleaved and degraded chemerin. This suggests that increased inflammation in individuals who have T2D or are IR causes more chemerin processing.

Identification and Physiological Assays of Crustacean Hyperglycemic Hormones in the Japanese Spiny Lobster, Panulirus japonicus.

The Japanese spiny lobster Panulirus japonicus lives on rocky shores and is mainly distributed along the Pacific coast around Japan. Due to the high demand for it, the development of aquaculture systems and increasing its resource volume requires further expansive production. However, a major factor preventing the establishment of aquaculture technology for this lobster is the difficulty with rearing processes from larval to juvenile production. A recent study shed light on the molecular mechanisms underlying larval development from the perspective of physiological functions of endocrine factors such as molting hormones. However, physiological studies of P. japonicus are still lacking. In decapod crustaceans, the X-organ/sinus gland complex is a well-known endocrine system that secretes the crustacean hyperglycemic hormone (CHH)-superfamily peptides that regulate growth, molting, sexual maturation, reproduction, and change in body color. In this study, we identified two CHHs from the sinus glands of P. japonicus using reversed-phase high-performance liquid chromatography in order to elucidate their physiological function for the first time.

Association between maternal fasting glucose levels throughout pregnancy and preschoolers' refractive errors.

PURPOSE: We aimed to investigate the association between maternal fasting plasma glucose (FPG) trajectories during pregnancy and children's refractive errors at 6 years old. DESIGN: Based on the Ma'anshan Birth Cohort (MABC) in China, a total of 1987 mother-child pairs were included in this study. METHODS: Using the group-based trajectory model, trajectory fitting was performed on fasting blood glucose levels during the first, second, and third trimesters of pregnancy. Children's vision was measured at 6 years of age using the standard logarithmic visual acuity E-chart and cycloplegic refraction examination. Logistic regression models and multi-informant generalized estimating equations were used to analyze the association between maternal blood glucose level and 6-year-old children's visual acuity. RESULTS: Children born of mothers with high level FPG trajectory had a higher risk of developing refractive error [OR=1.46 (95% CI 1.08 1.97)], hypermetropia [OR=1.64 (95% CI 1.09, 2.46)] and astigmatism [OR=1.60 (95% CI 1.06, 2.41)] at age six compared to those with low level trajectory. Maternal blood glucose level in the first [ß=-0.012 (95% CI -0.024, -0.001)] and the second [ß=-0.016 (95% CI -0.025, -0.006)] trimesters was associated with 6 year children's distance vision value. CONCLUSIONS: High level of fasting plasma glucose trajectories during pregnancy has been observed to be associated with 6-year-old children's refractive error, hypermetropia and astigmatism. The first and the second trimesters may be critical periods for the effects of maternal blood glucose on children's vision. The long-term effect of maternal glucose metabolism on children's visual development deserves further study.

Novel lipid mediator 7S,14R-docosahexaenoic acid: biogenesis and harnessing mesenchymal stem cells to ameliorate diabetic mellitus and retinal pericyte loss.

Introduction: Stem cells can be used to treat diabetic mellitus and complications. ω3-docosahexaenoic acid (DHA) derived lipid mediators are inflammation-resolving and protective. This study found novel DHA-derived 7S,14R-dihydroxy-4Z,8E,10Z,12E,16Z,19Z-docosahexaenoic acid (7S,14R-diHDHA), a maresin-1 stereoisomer biosynthesized by leukocytes and related enzymes. Moreover, 7S,14R-diHDHA can enhance mesenchymal stem cell (MSC) functions in the amelioration of diabetic mellitus and retinal pericyte loss in diabetic db/db mice. Methods: MSCs treated with 7S,14R-diHDHA were delivered into db/db mice i.v. every 5 days for 35 days. Results: Blood glucose levels in diabetic mice were lowered by 7S,14R-diHDHA-treated MSCs compared to control and untreated MSC groups, accompanied by improved glucose tolerance and higher blood insulin levels. 7S,14R-diHDHA-treated MSCs increased insulin+ ß-cell ratio and decreased glucogan+ α-cell ratio in islets, as well as reduced macrophages in pancreas. 7S,14R-diHDHA induced MSC functions in promoting MIN6 ß-cell viability and insulin secretion. 7S,14R-diHDHA induced MSC paracrine functions by increasing the generation of hepatocyte growth factor and vascular endothelial growth factor. Furthermore, 7S,14R-diHDHA enhanced MSC functions to ameliorate diabetes-caused pericyte loss in diabetic retinopathy by increasing their density in retina in db/db mice. Discussion: Our findings provide a novel strategy for improving therapy for diabetes and diabetic retinopathy using 7S,14R-diHDHA-primed MSCs.

A personalized multitasking framework for real-time prediction of blood glucose levels in type 1 diabetes patients.

Real-time prediction of blood glucose levels (BGLs) in individuals with type 1 diabetes (T1D) presents considerable challenges. Accordingly, we present a personalized multitasking framework aimed to forecast blood glucose levels in patients. The patient data was initially categorized according to gender and age and subsequently utilized as input for a modified GRU network model, creating five prediction sub-models. The model hyperparameters were optimized and tuned after introducing the decay factor and incorporating the TCN network and attention mechanism into the GRU model. This step was undertaken to improve the capability of feature extraction. The Ohio T1DM clinical dataset was used to train and evaluate the performance of the proposed model. The metrics, including Root Mean Square Error (RMSE), Mean Absolute Error (MAE) and Clark Error Grid Analysis (EGA), were used to evaluate the performance. The results showed that the average RMSE and the MAE of the proposed model were 16.896 and 9.978 mg/dL, respectively, over the prediction horizon (PH) of 30 minutes. The average RMSE and the MAE were 28.881 and 19.347 mg/dL, respectively, over the PH of 60 min. The proposed model demonstrated excellent prediction accuracy. In addition, the EGA analysis showed that the proposed model accurately predicted 30-minute and 60-minute PH within zones A and B, demonstrating that the framework is clinically feasible. The proposed personalized multitask prediction model in this study offers robust assistance for clinical decision-making, playing a pivotal role in improving the outcomes of individuals with diabetes.

Differences in physiology and behavior between male winner and loser mice in the tube test.

Social hierarchy is a crucial element for survival, reproduction, fitness, and the maintenance of a stable social group in social animals. This study aimed to investigate the physiological indicators, nociception, unfamiliar female mice preference, spatial learning memory, and contextual fear memory of male mice with different social status in the same cage. Our findings revealed significant differences in the trunk temperature and contextual fear memory between winner and loser mice. However, there were no major discrepancies in body weight, random and fasting blood glucose levels, whisker number, frontal and perianal temperature, spleen size, mechanical and thermal pain thresholds, preference for unfamiliar female mice, and spatial memory. In conclusion, social status can affect mice in multiple ways, and, therefore, its influence should be considered when conducting studies using these animals.

Sex- and time-specific associations of obesity with glycaemic traits: A two-step multivariate Mendelian randomization study.

AIM: To assess the sex- and time-specific causal effects of obesity-related anthropometric traits on glycaemic traits. MATERIALS AND METHODS: We used univariate and multivariate Mendelian randomization to assess the causal associations of anthropometric traits (gestational variables, birth weight, childhood body mass index [BMI], BMI, waist-to-hip ratio [WHR], BMI-adjusted WHR [WHRadj BMI]) with fasting glucose and insulin in Europeans from the Early Growth Genetics Consortium (n ≤ 298 142), the UK Biobank, the Genetic Investigation of Anthropometric Traits Consortium (n ≤ 697 734; females: n ≤ 434 794; males: n ≤ 374 754) and the Meta-Analyses of Glucose and Insulin-related traits Consortium (n ≤ 151 188; females: n ≤ 73 089; males: n ≤ 67 506), adjusting for maternal genetic effects, smoking, alcohol consumption, and age at menarche. RESULTS: We observed a null association for gestational variables, a negative association for birth weight, and positive associations for childhood BMI and adult traits (BMI, WHR, and WHRadj BMI). In female participants, increased birth weight causally decreased fasting insulin (betaIVW , -0.07, 95% confidence interval [CI] -0.11 to -0.03; p = 1.92 × 10-3 ), but not glucose levels, which was annulled by adjusting for age at menarche. In male participants, increased birth weight causally decreased fasting glucose (betainverse-variance-weighted (IVW) , -0.07, 95% CI -0.11 to -0.03; p = 3.22 × 10-4 ), but not insulin levels. In time-specific analyses, independent effects of birth weight were absent in female participants, and were more pronounced in male participants. Independent effects of childhood BMI were attenuated in both sexes; independent effects of adult traits differed by sex. CONCLUSIONS: Our findings provide evidence for causal and independent effects of sex- and time-specific anthropometric traits on glycaemic variables, and highlight the importance of considering multiple obesity exposures at different time points in the life course.

Metabolic Disorders During Prolactinomas.

The metabolic profile during prolactinoma may be subject to significant changes. We aimed to describe the different metabolic aspects in patients monitored for prolactinoma and to study the correlations between the size of the prolactinoma and the metabolic parameters. We conducted a retrospective, descriptive, and analytical study of 77 cases of prolactinomas collected and monitored at the endocrinology and diabetology department of the Hedi Chaker Hospital in Sfax between 2000 and 2017. Our patients were divided into three groups according to the size of their prolactinomas. Statistical correlations were sought between tumor size and clinical and biological parameters. The mean age of our patients was 38.3 ± 14.2 years. They were divided into 51 women (66.2%) and 26 men (33.7%). Pituitary tumor syndrome was the most common circumstance of discovery in our population (62.3%). The clinical examination revealed an average waist circumference of 95.71 cm. Android fat distribution was observed in 25 women (49%) and 12 men (46.1%). A statistically significant positive correlation was objectified between waist circumference and tumor size (r = 0.29 and P = 0.019). The average body mass index was 28.08 kg/m2. Obesity was noted in 56 cases (72.7%). Glucose tolerance disorders and hypertriglyceridemia were also more evident each time prolactinoma size increased in contrast to the level of high-density lipoprotein cholesterol which decreased with adenoma size. Our study highlighted the metabolic and hormonal repercussions of prolactinomas. Metabolic syndrome was more common in patients with larger prolactinoma. These results should guide the initial assessment and therapeutic management of prolactin adenomas.

Metabolic consequences of flavonoid and saponin extracts from Gongronema Latifolium leaves in offspring of rats that consumed sucrose during lactation.

Objectives: This study examines the metabolic consequences of saponin and flavonoid extracts of Gongronema latifolium leaves in rat offspring whose mothers consumed sucrose during breastfeeding. Methods: Thirty-two female albino Wistar rats were randomly assigned to control group, given water only: sucrose group, given sucrose solution only; flavonoid groups, given sucrose solution and 100 mg/kg b.w. and 200 mg/kg b.w. of flavonoid and saponin groups, given sucrose solution and 100 mg/kg b.w. and 200 mg/kg b.w. of saponin extracts, for 3 weeks during lactation. Then the body, hepatic and pancreatic weights, food intake, glucose tolerance, lipid profile, insulin, and leptin levels of their offspring were measured. Results: There was a significant decrease in the body weight (BW), food intake, and glucose level among the flavonoid and saponin groups compared to the control group. However, when compared to the sucrose group, there was a significant decrease in food intake, blood glucose level, triglyceride, and very low-density lipoprotein cholesterol levels and a significant increase in the BW. There was no significant difference in insulin and leptin levels, hepatic, and pancreatic weights among groups. Conclusion: This study shows that G. lactifolium consumption among lactating rats maintains metabolic homeostatic as it protects against elevated blood glucose level and dyslipidemia in offspring post-weaning. It also suggests that the hypoglycemic and hypolipidemic properties of G. latifolium maybe as a result of saponin and flavonoids inherent in the plant.

Automated blood glucose regulation for nonlinear model of type-1 diabetic patient under uncertainties: GWOCS type-2 fuzzy approach.

Regulating blood glucose level (BGL) for type-1 diabetic patient (T1DP) accurately is very important issue, an uncontrolled BGL outside the standard safe range between 70 and 180 mg/dl results in dire consequences for health and can significantly increase the chance of death. So the purpose of this study is to design an optimized controller that infuses appropriate amounts of exogenous insulin into the blood stream of T1DP proportional to the amount of obtained glucose from food. The nonlinear extended Bergman minimal model is used to present glucose-insulin physiological system, an interval type-2 fuzzy logic controller (IT2FLC) is utilized to infuse the proper amount of exogenous insulin. Superiority of IT2FLC in minimizing the effect of uncertainties in the system depends primarily on the best choice of footprint of uncertainty (FOU) of IT2FLC. So a comparison includes four different optimization methods for tuning FOU including hybrid grey wolf optimizer-cuckoo search (GWOCS) and fuzzy logic controller (FLC) method is constructed to select the best controller approach. The effectiveness of the proposed controller was evaluated under six different scenarios of T1DP using Matlab/Simulink platform. A 24-h scenario close to real for 100 virtual T1DPs subjected to parametric uncertainty, uncertain meal disturbance and random initial condition showed that IT2FLC accurately regulate BGL for all T1DPs within the standard safe range. The results indicated that IT2FLC using GWOCS can prevent side effect of treatment with blood-sugar-lowering medication. Also stability analysis for the system indicated that the system operates within the stability region of nonlinear system.