Increased Blood Glucose Levels Research Articles

Clinical Observation of Hfnc Use Along With Non-rebreather Mask on Critical Covid-19 Diabetic Patients

Purpose: This study aimed to observe and compare the efficacy of High-flow Nasal Cannula (HFNC) with/without a non-rebreather mask (NRM) on ICU-admitted COVID-19 diabetic patients.
 Methodology: We collected epidemiological, biochemical, and clinical information from patients (diabetic = 136; non-diabetic = 104) admitted into four hospitals in Chattogram, Bangladesh. SPSS v25 was used to analyze the data with the Chi-Square, Fisher’s Exact, and Independent Samples T-test. We also built regression models to find out the impact of the variables.
 Results: Most of the patients with fever (59.1%) and hypertension (68.3%) had diabetes. We also noticed diabetic patients stayed in ICU longer (9.06±5.70) than non-diabetic patients (7.41±5.11). Moreover, elevated creatinine level was found in most diabetic cases (70.4%). After only HFNC administration, the partial pressure of oxygen significantly improved in non-diabetic patients. However, both diabetic and non-diabetic patients were observed to have an almost equal partial pressure of oxygen after HFNC with NRM management. Patients with elevated blood sugar additionally needed NRM more than fivefold compared to those with normal blood sugar levels. Besides, age and hypertension were significantly associated with HFNC+NRM-treated diabetic patients.
 Future Implications: The results of this study imply that oxygen supply with HFNC and NRM may be beneficial for elderly/hypertensive diabetic patients with COVID-19-associated AHRF; and that increased blood glucose level could be a determinant for the need for HFNC + NRM treatment.
 Bioresearch Commu. 9(2): 1285-1296, 2023 (July)

146-OR: Causative Role of Hypothalamic Ventromedial Glucose-Inhibited Neurons in Impaired Counterregulatory Responses to Hypoglycemia

The development of impaired counterregulatory responses (CRR) after recurrent hypoglycemia (RH) is one of the most life-threatening and debilitating aspects of Type 1 Diabetes (T1D). Numerous scientific evidence points to the ventromedial nucleus of the hypothalamus (VMH) glucose-inhibited (GI) neurons as major players in the development of impaired CRR. However, there is no current evidence of a causative role of VMH GI neurons in impaired CRR. In this study, we used a protocol in which mice were injected with insulin (2.5 U/kg, i.p.) for 4 consecutive days. These mice displayed impaired CRR after 2-deoxy-D-glucose (2-DG) administration (200 mg/kg, i.p. injected on the 5th day) with blunted levels of circulating glucose, corticosterone, and epinephrine in comparison to mice with intact CRR after 2-DG administration. Using a TRAP2:tdTomato mouse model, we labeled (tdTomato) GI neurons by injecting 4-hydroxytamoxifen after 2-DG administration. Four weeks later, the mice were injected with either insulin or vehicle for 4 days followed by 2-DG administration, of which the brains were then immunostained and analyzed for cFos in the VMH. We observed a significant decrease in double-labeled tdTomato/cFos cells in mice with impaired CRR compared to the controls, thus suggesting an altered VMH GI neuronal activation following insulin-induced RH. In support of this, chemogenetic activation of VMH GI neurons in mice with impaired CRR significantly increased blood glucose levels following 2-DG administration compared to mice with impaired CRR. Overall, our data provide evidence for a direct and causal involvement of VMH GI neurons in the development of impaired CRR following RH. Disclosure F.Copperi: None. X.Shen: None. S.Diano: None. Funding Naomi Berrie Diabetes Center; National Institute of Diabetes and Digestive and Kidney Diseases (DK107293)

Analysis Of The Relationship Between HBA1C and Serum Galectin-3 Levels in Subjects With Type 2 Of Diabetes Mellitus

<div><table cellspacing="0" cellpadding="0" align="left"><tbody><tr><td align="left" valign="top"><p><em>Type 2 diabetes mellitus is a disease characterized by increased blood glucose levels known as hyperglycemia. This disease can be diagnosed by examining HbA1c (glycated hemoglobin). Hemoglobin A1c is a minor component of hemoglobin related to glucose. Meanwhile, galectin-3 is a protein encoded in humans by the LGALS3 gene. This study aimed to clarify the relationship between HbA1c and serum galectin-3 levels in patients with type 2 diabetes. This study was conducted using an observational analysis technique with a cross-sectional study design</em><em>. This research was conducted at the Clinical Pathology Laboratory, Hasanuddin University State University Hospital, and Laboratorium Universitas Hasanuddin Medical Research Center State College Hospital Universitas Hasanuddin Makassar</em><em>. This research was conducted from January to March 2023</em><em>. </em><em>The population in this study were all patients with type 2 DM who visited the Hasanuddin University Hospital (RSPTN-UH) for treatment a total of 112 patients</em><em>. Research sampling technique with non-probability purposive sampling. The sample of this study was 60 patients. Data analysis with the Independent T-test or Mann-Whitney test. The results of the study were that serum Galectin-3 levels in uncontrolled type 2 diabetes mellitus had a higher average value of 20.18 ± 6.15 ng/mL compared to controlled type 2 diabetes mellitus, namely 14.80 ± 6.41 ng/ mL although there was a statistically significant difference (p=0.012) but no significant correlation was found between HbA1c and serum Galectin-3 levels in type 2 diabetes mellitus subjects (r=0.176 p=0.179) with the distribution of data in the Scatterplot not forming a linear relationship pattern</em><em>. </em><em>It is recommended that type 2 Diabetes Mellitus patients carry out an HbA1c examination as an effective test to control glucose levels, reduce the risk of complications, and maintain a healthy lifestyle to avoid type 2 DM.</em></p><p><em><br /></em></p></td></tr></tbody></table></div><strong><em>Keyword: HbA1c, Serum Galectin-3, Type 2 Diabetes Mellitus</em></strong>

Phytotherapy for Diabetes: An Overview of Indian Traditional Plants with Saponins as a Phytoconstituent

The present article consists of the basic knowledge about diabetes with its classification as Type 1, Type 2, gestational diabetes as well as other types of diabetes mellitus (DM). Diabetes mellitus is a long-term metabolic disorder defined by increased blood glucose levels. Insulin secretion and action are defective in diabetic patients. Diabetes leads to irreversible damage and failure of many organs because of chronic hyperglycemia. They have a complex etiology that arises when the equilibrium of offensive and protective components is altered. The limited effectiveness and severe adverse effects of the currently available medications make treatment extremely difficult. In experimental models of anti-diabetic preparations, natural items such as herbal plants and their extracted components have been frequently used. Saponins, a glycosidic molecule, is proven to have therapeutic potential and they are used as an alternative treatment for insulin in diabetic patients. Saponin-induced dyslipidemia will aid diabetic people in lowering their risk of cardiovascular disease and atherosclerosis. This review aims to explain the antidiabetic function of saponins as well as its potential in the management of diabetes.

Comparative analysis of predictive machine learning algorithms for diabetes mellitus

Diabetes mellitus (DM) is a serious worldwide health issue, and its prevalence is rapidly growing. It is a spectrum of metabolic illnesses defined by perpetually increased blood glucose levels. Undiagnosed diabetes can lead to a variety of problems, including retinopathy, nephropathy, neuropathy, and other vascular abnormalities. In this context, machine learning (ML) technologies may be particularly useful for early disease identification, diagnosis, and therapy monitoring. The core idea of this study is to identify the strong ML algorithm to predict it. For this several ML algorithms were chosen i.e., support vector machine (SVM), Naïve Bayes (NB), K nearest neighbor (KNN), random forest (RF), logistic regression (LR), and decision tree (DT), according to studied work. Two, Pima Indian diabetic (PID) and Germany diabetes datasets were used and the experiment was performed using Waikato environment for knowledge analysis (WEKA) 3.8.6 tool. This article discussed about performance matrices and error rates of classifiers for both datasets. The results showed that for PID database (PIDD), SVM works better with an accuracy of 74% whereas for Germany KNN and RF work better with 98.7% accuracy. This study can aid healthcare facilities and researchers in comprehending the value and application of ML algorithms in predicting diabetes at an early stage.

Metabolic outcomes and changes in innate immunity induced by diesel exhaust particles airway exposure and high-fat high-sucrose diet

AimsEpidemiological studies have shown that exposure to diesel exhaust particles (DEP) is associated with metabolic diseases. We used mice with nonalcoholic fatty liver disease (NAFLD) caused by a high-fat, high-sucrose diet (HFHSD), which mimics a Western diet, to investigate the mechanism of NAFLD exacerbation via changes in innate immunity in the lungs by airway exposure to DEP. Main methodsSix-week-old C57BL6/J male mice were fed HFHSD, and DEP was administered endotracheally once a week for eight weeks. The histology, gene expression, innate immunity cells in the lung and liver, and the serum inflammatory cytokine levels, were investigated. Key findingsUnder the HFHSD, DEP increased blood glucose levels, serum lipid levels, and NAFLD activity scores, and also the expression of genes associated with inflammation in the lungs and liver. DEP caused an increase in ILC1s, ILC2s, ILC3s, and M1 macrophages in the lungs and a marked increase in ILC1s, ILC3s, M1 macrophages, and natural killer cells in the liver, while ILC2 levels were not changed. Furthermore, DEP caused high levels of inflammatory cytokines in the serum. SignificanceChronic exposure to DEP in HFHSD-fed mice increased inflammatory cells involved in innate immunity in the lungs and raised local inflammatory cytokine levels. This inflammation spread throughout the body, suggesting the association with the progression of NAFLD via increased inflammatory cells involved in innate immunity and inflammatory cytokine levels in the liver. These findings contribute to a better understanding of the role of innate immunity in air pollution-related systemic diseases, especially metabolic diseases.

IN SILICO STUDY OF APTAMER SPECIFICITY FOR DETECTION OF ADENOSINE TRIPHOSPHATE (ATP) AS BIOSENSOR DEVELOPMENT FOR MITOCHONDRIA DIABETES DIAGNOSIS

Diabetes Mellitus (DM) is characterized by increased blood glucose levels. It is generally caused by the pancreas' inability to produce insulin due to cell damage or insulin resistance. Due to the inhibition of adenosine triphosphate (ATP) production, which is essential for insulin secretion, one clinical pathology of this complication is insulin secretion dysfunction. Common methods of blood sugar diagnostics cannot distinguish mitochondrial diabetes and can lead to medication errors. Furthermore, an approach was developed through ATP biomarkers using an electrochemical biosensor with the help of an aptamer. However, it remains unknown precisely how and where the molecular interactions between the modified aptamer and ATP occur. Simulations were conducted in this study for 100 ns in silico using the amber18 computer program to determine the stability of the interaction and specificity between aptamer-ATP were compared to ADP and AMP. The results showed that the significant interactions are three hydrogen bonds between ATP and G7, G8, and A24. It was discovered that the aptamer-ATP complex had moderately good interaction and better potential for specificity than ADP and AMP. According to the RMSD, RMSF, and binding energy profiles, the system is still searching for the best conformation, necessitating a longer simulation time and additional studies to optimize the system. As a result, the system can reach a stable state and determine a more accurate energy calculation, hence, it is interpreted according to real applications.

How does l-theanine treatment affect the levels of serum and hippocampal BDNF, insulin and adipocytokines in diabetic rats?

BackgroundDiabetes Mellitus (DM), a metabolic disease characterized by the increased blood glucose level, insulin deficiency or ineffectiveness, may cause structural and functional disorders in the brain. l-Theanine (LTN) has the relaxing, psychoactive, antidepressant, anti-inflammatory and antinecrotic properties, and regulates the functions of hippocampus (HP) in brain. In the present study, the aim was to identify the effects LTN on the levels of BDNF, insulin and adipocytokines (TNF-α, leptin, adiponectin and resistin) in both HP and serum of diabetic rats. Methods32 male Wistar rats were divided into four groups (n = 8/group): Control, LTN, DM and DM + LTN. Diabetes was induced by by nicotinamide/streptozotocin. 200 mg/kg/day LTN treatment was applied for 28 days. The serum and hippocampal levels of the parameters were determined by using commercial ELISA kits. Additionally, HP tissues examined histopathologically. ResultsLTN treatment significantly decreased leptin and adiponectin levels in HP tissues in diabetic rats (p < 0.05). Although it decreased the insulin level in both serum and HP, this was not statistically significant. No significant effect on other parameters was observed (p > 0.05). In histopathological analysis, although the damage was reduced by LTN in all sections of HP, this change was significant mainly in CA3 region (p < 0.05). ConclusionIt was concluded that LTN has the ability to reduce hippocampal degeneration and modulates adipocytokines in diabetic rats.

In Silico and In Vivo Studies of Decursin Isolated From the Ethanolic Extract of Feronia elephantum Correa (Rutaceae) Bark as a Potential Antidiabetic and Antihyperlipidemic Agents in STZ-induced Diabetic Rats

Background: Feronia elephantum (Rutaceae), frequently named wood apple, is a preferable medicinal plant. In Ayurveda, its bark has been recommended for treating diabetes. In addition, it is one of the active chemical constituents, decursin, shown in recent research to significantly impact colon cancer, breast cancer, Alzheimer's disease, inflammation, and ulcerative colitis. Objective: The present study was carried out to investigate the traditional use of Feronia elephantum bark in streptozotocin-induced diabetes and lipid-lowering action in rats. Decursin has been isolated from the bark and tested for in vitro and in vivo biological activities. Methods: The Soxhlet extraction method obtained the ethanolic extract, and fractionation was done with column chromatography and TLC. The structure of isolated decursin has been confirmed by Fourier transform infrared (FTIR) and nuclear magnetic resonance (NMR) spectroscopy. Results: The decursin noticeably depletes increased blood glucose levels and positively affects altered lipid profiles after administering a dose of 150 mg/kg orally compared with the hypoglycemic drug metformin. In molecular docking simulations, decursin exhibited excellent inhibition of α-amylase, dipeptidyl peptidase-IV, and moderate activity against α-glucosidase and glucokinase. Furthermore, the enzymes 3- hydroxy-3-methylglutaryl coenzyme A and Niemann-Pick C1-Like 1 are ideal targets to control hyperlipidemia and have shown moderate inhibition by decursin. Conclusion: From these results, it has been concluded that decursin is the perfect candidate for further optimization as a lead molecule to treat diabetes and hyperlipidemia.

Brain circuits underlying the sympathetic control of the liver

The sympathetic nervous system plays an important role in the maintenance of hepatic glucose homeostasis, through stimulating glucose production and glycogenolysis. Pre-sympathetic neurons in the brainstem and hypothalamus govern the sympathetic output to the liver and thus control hepatic metabolism and glycemia. Intriguingly, despite the importance of this central pathway, specific information regarding the neural circuits and properties of liver-related neurons is limited. In this study, we tested the hypothesis that liver-related neurons in the paraventricular nucleus of the hypothalamus (PVN) and ventral lateral medulla of the brainstem (VLM) are part of a pre-sympathetic central circuit that is involved in the control of energy intake and regulation of glucose homeostasis. First, liver-related neurons were identified with a retrograde trans-synaptic viral tracer and their phenotype was revealed. In the VLM, ~23.2% of liver-related neurons expressed Dopamine Beta Hydroxylase (n=5) and ~9.3% Tyrosine Hydroxylase (n=6), which is consistent with previous reports demonstrating that catecholaminergic neurons in the VLM play a critical role in glucose regulation. In the PVN, ~6.8% of liver-related neurons expressed oxytocin (n=7) and ~27.5% expressed Single Minded 1 (Sim1) protein (n=7), two major neuronal populations in the PVN known for their involvement in the regulation of energy metabolism. Next, pre-sympathetic liver-related PVN neurons with projections to the VLM were identified and optogenetic approach was used to reveal functional connections between PVN neurons and pre-sympathetic liver-related neurons in the VLM. Light stimulation of projections of Sim1-expressing PVN neurons resulted in evoked excitatory postsynaptic currents in a subset of liver-related VLM neurons, which suggests the existence of monosynaptic connections between PVN and pre-sympathetic liver-related neurons in the VLM. Then the involvement of pre-sympathetic, VLM-projecting PVN neurons was determined in the regulation of energy homeostasis using chemogenetic approaches. Stimulation of VLM-projecting PVN neurons increased blood glucose levels (basal=137± 6 mg/dl vs. CNO (1mg/kg)=181± 12 mg/dl; paired t-test P=0.01, n=9) and decreased food intake during refeeding (two way ANOVA on paired and repeated measures, P&lt;0.0001, n=9), while the respiratory exchange ratio and locomotor activity were not altered. In summary, our data strongly suggest the existence of a central circuit involving direct connections between pre-sympathetic PVN and catecholaminergic, liver-related VLM neurons and demonstrate that these neurons are involved in the regulation of energy homeostasis. Moreover, these results provide novel information about the pre-sympathetic central circuits involved in the regulation of the liver, and thus energy homeostasis and are crucial for the development of new strategies to improve glucose homeostasis via the autonomic nervous system. NIDDK122842 and Tulane Brain Institute Marko Spark Innovation Research Fund This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

The effect of 6% hydroxyethyl starch 130/0.4 preloading on the blood glucose levels in diabetic patients undergoing orthopedic surgery with spinal anesthesia: a randomized pilot study.

Perioperative hyperglycemia can occur in surgical patients and may increase postoperative morbidity and mortality, especially in patients with diabetes. Therefore, we conducted the present study to evaluate whether the administration of 6% hydroxyethyl starch (HES)-130/0.4 increases blood glucose levels in patients with diabetes. Forty patients undergoing lower limb surgery under spinal anesthesia were randomly allocated into two groups according to the fluids administered 20 min before spinal anesthesia (Group L, lactated Ringer's solution; Group H, 6% HES-130/0.4). Patient characteristics, intraoperative variables, blood glucose levels, mean blood pressure (MBP), and heart rate (HR) were recorded at five time-points (0, 20, 60, 120, and 240 min). A total of 39 patients were analyzed (Group L, n = 20; Group H, n = 19). The amount of intraoperative fluid was significantly higher in Group L than in Group H (718.2 ml vs. 530.0 ml, P = 0.010). There were no significant differences in the changes in blood glucose levels, HR, or MBP between the two groups (P = 0.737, P = 0.896, and P = 0.141, respectively). Serial changes in mean blood glucose levels from baseline also showed no significant differences between the groups (P = 0.764). There were no significant changes in blood glucose levels when lactated Ringer's solution or 6% HES-130 was used. When compared to the lactated Ringer's solution, no evidence that 6% HES-130/0.4 produces hyperglycemia in diabetic patients could be found. Further evaluation of larger populations is needed.

The dietary regulation of LEAP2 depends on meal composition in mice.

Ghrelin represents a key hormone regulating energy balance. Upon activation of the growth hormone secretagogue receptor (GHSR), ghrelin increases blood glucose levels, food intake, and promotes weight gain. The liver-expressed antimicrobial peptide 2 (LEAP2) acts as an endogenous antagonist of the GHSR. While the regulation of LEAP2 and its effect on the GHSR likely occur in an opposite pattern to that of ghrelin, the dietary regulation of LEAP2 remains to be described. We, therefore, examined the regulation of LEAP2 by different acute meal challenges (glucose, mixed meal, olive, lard, and fish oil) and diets (chow vs. high-fat) in C57BL/6 male mice. In addition, the effect of specific fatty acids (oleic, docosahexaenoic, and linoleic acid) on LEAP2 was assessed in murine intestinal organoids. While only mixed meal increased liver Leap2 expression, all meal challenges except fish oil increased jejunal Leap2 expression compared to water. Leap2 expression correlated with levels of hepatic glycogen and jejunal lipids. Lipid versus water dosing increased LEAP2 levels in the systemic circulation and portal vein where fish oil was associated with the smallest increase. In line with this, oleic acid, but not docosahexaenoic acid increased Leap2 expression in intestinal organoids. Feeding mice with high-fat versus chow diet not only increased plasma LEAP2 levels, but also the increment in plasma LEAP2 upon dosing with olive oil versus water. Taken together, these results show that LEAP2 is regulated by meal ingestion in both the small intestine and the liver according to the meal/diet of interest and local energy stores.

Mexican Plants Involved in Glucose Homeostasis and Body Weight Control: Systematic Review

Background: Obesity is defined as abnormal or excessive fat accumulation, provoking many different diseases, such as obesity and type 2 diabetes. Type 2 diabetes is a chronic-degenerative disease characterized by increased blood glucose levels. Obesity and type 2 diabetes are currently considered public health problems, and their prevalence has increased over the last few years. Because of the high cost involved in the treatment of both diseases, different alternatives have been sought. However, the general population uses medicinal plants, in the form of tea or infusions, to treat different diseases. Therefore, traditional medicine using medicinal plants has been investigated as a possible treatment for type 2 diabetes and body weight control. Aim of the study: The purpose of this review is to find medicinal plants used in Mexico that could exert their beneficial effect by regulating insulin secretion and body weight control. Material and method: For the development of this review, Mexican plants used in traditional medicine to treat type 2 diabetes and body weight control were searched in PubMed, Google Scholar, and Scopus. The inclusion criteria include plants that presented a significant reduction in blood glucose levels and/or an increase in insulin secretion. Results: We found 306 Mexican plants with hypoglycemic effects. However, plants that did not show evidence of an increase in insulin secretion were eliminated. Finally, only five plants were included in this review: Momordica charantia L. (melón amargo), Cucurbita ficifolia bouché (chilacayote), Coriandrum sativum L. (cilantro), Persea americana Mill. (aguacate) Bidens pilosa (amor seco), including 39 articles in total. Here, we summarized the plant extracts (aqueous and organic) that have previously been reported to present hypoglycemic effects, body weight control, increased secretion and sensitivity of insulin, improvement of pancreatic β cells, and glucose tolerance. Additionally, these effects may be due to different bioactive compounds present in the plants’ extracts. Conclusion: Both in vivo and in vitro studies are required to understand the mechanism of action of these plant extracts regarding insulin secretion to be used as a possible treatment for type 2 diabetes and body weight control in the future.

Evaluation of Antidiabetic Activity of Oxadiazole Derivative in Rats.

The oxadiazole ring has long been used for the treatment of several diseases. This study aimed to analyze the antihyperglycemic and antioxidant roles of the 1,3,4-oxadiazole derivative with its toxicity. Diabetes was induced through intraperitoneal administration of alloxan monohydrate at 150 mg/kg in rats. Glimepiride and acarbose were used as standards. Rats were divided into groups of normal control, disease control, standard, and diabetic rats (treated with 5, 10, and 15 mg/kg of 1,3,4-oxadiazole derivative). After 14 days of oral administration of 1,3,4-oxadiazole derivatives (5, 10, and 15 mg/kg) to the diabetic group, the blood glucose level, body weight, glycated hemoglobin (HbA1c), insulin level, antioxidant effect, and histopathology of the pancreas were performed. The toxicity was measured by estimating liver enzyme, renal function, lipid profile, antioxidative effect, and liver and kidney histopathological study. The blood glucose and body weight were measured before and after treatment. Alloxan significantly increased blood glucose levels, HbA1c, alanine transaminase, aspartate aminotransferase, urea, cholesterol, triglycerides, and creatinine. In contrast, body weight, insulin level, and antioxidant factors were reduced compared to the normal control group. Treatment with oxadiazole derivatives showed a significant reduction in blood glucose levels, HbA1c, alanine transaminase, aspartate aminotransferase, urea, cholesterol, triglycerides, and creatinine as compared to the disease control group. The 1,3,4-oxadiazole derivative significantly improved body weight, insulin level, and antioxidant factors compared to the disease control group. In conclusion, the oxadiazole derivative showed potential antidiabetic activity and indicated its potential as a therapeutic.

Molecular Modeling and Synthesis of Indoline-2,3-dione-Based Benzene Sulfonamide Derivatives and Their Inhibitory Activity against α-Glucosidase and α-Amylase Enzymes.

Diabetes is also known as a critical and noisy disease. Hyperglycemia, that is, increased blood glucose level is a common effect of uncontrolled diabetes, and over a period of time can cause serious effects on health such as blood vessel damage and nervous system damage. However, many attempts have been made to find suitable and beneficial solutions to overcome diabetes. Considering this fact, we synthesized a novel series of indoline-2,3-dione-based benzene sulfonamide derivatives and evaluated them against α-glucosidase and α-amylase enzymes. Out of the synthesized sixteen compounds (1-16), only three compounds showed better results; the IC50 value was in the range of 12.70 ± 0.20 to 0.90 ± 0.10 μM for α-glucosidase against acarbose 11.50 ± 0.30 μM and 14.90 ± 0.20 to 1.10 ± 0.10 μM for α-amylase against acarbose 12.20 ± 0.30 μM. Among the series, only three compounds showed better inhibitory potential such as analogues 11 (0.90 ± 0.10 μM for α-glucosidase and 1.10 ± 0.10 μM for α-amylase), 1 (1.10 ± 0.10 μM for α-glucosidase and 1.30 ± 0.10 μM for α-amylase), and 6 (1.20 ± 0.10 μM for α-glucosidase and 1.60 ± 0.10 μM for α-amylase). Molecular modeling was performed to determine the binding affinity of active interacting residues against these enzymes, and it was found that benzenesulfonohydrazide derivatives can be indexed as suitable inhibitors for diabetes mellitus.

Carnosine-Based Reversal of Diabetes-Associated Cognitive Decline via Activation of the Akt/mTOR Pathway and Modulation of Autophagy in a Rat Model of Type 2 Diabetes Mellitus

Introduction: Carnosine can suppress secondary complications in diabetes and show robust neuroprotective activity against neurodegenerative diseases. Here, we report that carnosine ameliorates diabetes-associated cognitive decline in vivo through the modulation of autophagy. Methods: A high-fat diet (HFD) and one intraperitoneal injection of 30 mg/kg streptozotocin (STZ) were used to induce type 2 diabetes mellitus in Sprague-Dawley rats. The rats were randomly divided into five groups: control (CON), HFD/STZ, and three intragastric carnosine treatment groups receiving low (100 mg/kg), medium (300 mg/kg), and high (900 mg/kg) doses over 12 weeks. Body weight, blood glucose levels, and cognitive function were continuously monitored. From excised rat hippocampi, we determined superoxide dismutase (SOD) activity and malondialdehyde (MDA) levels; carnosine concentration; protein expressions of Akt, mTOR and the autophagy markers LC3B and P62 and performed histopathological evaluations of the cornu ammonis 1 region. Results: The HFD/STZ group showed increased blood glucose levels and decreased body weight compared to the CON group. However, there were no significant differences in body weight and blood glucose levels between carnosine-treated and -untreated HFD-STZ-induced diabetic rats. Diabetic animals showed obvious learning and memory impairments in the Morris water maze test compared to the CON group. Compared to those in the HFD/STZ group, carnosine increased SOD activity and decreased MDA levels, increased hippocampal carnosine concentration, increased p-Akt and p-mTOR expression, decreased LC3B and P62 expression, alleviated neuronal injuries, and improved cognitive performance in a dose-dependent manner. Conclusion: Independent of any hyperglycemic effect, carnosine may improve mild cognitive impairments by mitigating oxidative stress, activating the Akt/mTOR pathway, and modulating autophagy in the hippocampus of type 2 diabetic rats.

Mastication inefficiency due to diminished or lack of occlusal support is associated with increased blood glucose levels in patients with type 2 diabetes.

It has been shown that mastication may contribute to a lower risk of diabetes, and occlusal support reduced the risk of diabetes by improving glucose metabolism after meals. However, the relationship between inefficient mastication and blood glucose levels in patients with type 2 diabetes (T2D) remains unclear. This retrospective study, therefore, aimed to investigate the association between mastication inefficiency due to diminished occlusal support and blood glucose control in subjects with T2D. Ninety-four subjects (mean of 54.9 years) were recruited in this study. Subjects with at least 1-year T2D medical history and current medications for T2D were included. Subjects were divided into 2 groups: The control group (41 subjects) included Eichner group A (4 occlusal functional areas in the posterior area). The test group (53 subjects) included Eichner group B (1-3 occlusal functional areas) and group C (no natural occlusal contact). Blood glucose level was significantly lower in the control group participants than in the test group. Subject(s) showing diminished or lack of occlusal support and requiring a fixed restoration were treated with an implant-supported fixed restoration. These groups' levels of glycated hemoglobin (A1c) were compared using the independent student t-test. Blood glucose level was significantly lower in the control group (7.48) as compared to those in the test group (9.42). The mean differences between the two groups were 1.94 ± 0.39 (p = 0.0001). Differences in white blood cell counts and body mass index (BMI) were not statistically significant between groups. Blood glucose levels could be reduced (from A1c 9.1 to 6.2) following a fixed implant-supported restoration in T2D patients with diminished occlusal support. The results suggested that masticatory inefficiency due to diminished dental occlusion was associated with an increase in poor controlled-blood glucose levels among T2D patients.

Lymphocytes regulate expression of the SARS-CoV-2 cell entry factor ACE2 in the pancreas of T2DM patients.

COVID-19 patients with type 2 diabetes mellitus (T2DM) show both poorer clinical outcomes and have an increased risk of death. SARS-CoV-2 virus infection requires simultaneous expression of the SARS-CoV-2 cell entry factors angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine type 2 (TMPRSS2) in the same cell. The aim of the study was to explore the underlying mechanisms of a COVID-19 infection in patients with T2DM. The distribution and expression of AEC2 and TMPRSS2 in different pancreatic cell types in clinical samples of T2DM patients and diabetic mouse models were analysed by single-cell sequencing, bioinformatics analysis and basic experiments. The results showed that ACE2 and TMPRSS2 are expressed in the ducts of the human pancreas. These findings suggest that SARS-CoV-2 can infect ductal cells in vivo through ACE2 and TMPRSS2. T2DM can promote the co-expression of ACE2 and TMPRSS2 in exocrine ducts, including in the human pancreas. We hypothesize that ACE2 expression levels are associated with increased numbers of lymphocytes in vivo. Increased blood glucose levels are associated with increased ACE2 expression and an increased number of lymphocytes. At the same time, lymphocytes can promote ACE2 expression.

GCK exonic mutations induce abnormal biochemical activities and result in GCK-MODY.

Objective: Glucokinase-maturity-onset diabetes of the young (GCK-MODY; MODY2) is a rare genetic disorder caused by mutations in the glucokinase (GCK) gene. It is often under- or misdiagnosed in clinical practice, but correct diagnosis can be facilitated by genetic testing. In this study, we examined the genes of three patients diagnosed with GCK-MODY and tested their biochemical properties, such as protein stability and half-life, to explore the function of the mutant proteins and identify the pathogenic mechanism of GCK-MODY. Methods: Three patients with increased blood glucose levels were diagnosed with MODY2 according to the diagnostic guidelines of GCK-MODY proposed by the International Society for Pediatric and Adolescent Diabetes (ISPAD) in 2018. Next-generation sequencing (whole exome detection) was performed to detect gene mutations. The GCK gene and its mutations were introduced into the pCDNA3.0 and pGEX-4T-1 vectors. Following protein purification, enzyme activity assay, and protein immunoblotting, the enzyme activity of GCK was determined, along with the ubiquitination level of the mutant GCK protein. Results: Genetic testing revealed three mutations in the GCK gene of the three patients, including c.574C>T (p.R192W), c.758G>A (p.C253Y), and c.794G>A (p.G265D). The biochemical characteristics of the protein encoded by wild-type GCK and mutant GCK were different, compared to wild-type GCK, the enzyme activity encoded by the mutant GCK was reduced, suggesting thermal instability of the mutant GST-GCK. The protein stability and expression levels of the mutant GCK were reduced, and the enzyme activity of GCK was negatively correlated with the levels of fasting blood glucose and HbA1c. In addition, ubiquitination of the mutant GCK protein was higher than that of the wild-type, suggesting a higher degradation rate of mutant GCK than WT-GCK. Conclusion: GCK mutations lead to changes in the biochemical characteristics of its encoded proteins. The enzyme activities, protein expression, and protein stability of GCK may be reduced in patients with GCK gene mutations, which further causes glucose metabolism disorders and induces MODY2.

Faktor Risiko Kejadian Diabetes Melitus Tipe 2 Pada Pasien Rawat Jalan Di RSUD Sanjiwani Gianyar

Diabetes mellitus (DM) is a chronic disease characterized by increased blood glucose levels and is the fourth leading cause of death worldwide. The majority of diabetes mellitus sufferers worldwide are type 2 DM. The prevalence of DM continues to increase due to multifactorial changes in people's lifestyles and eating patterns. This study aimed to determine the risk factors associated with type 2 DM in outpatients at Sanjiwani Hospital, Gianyar. It was case-control with a consecutive sampling technique. The number of samples was 138 people, and they were analyzed using the Chi-Square test. Data was collected by interview and physical examination. The results of the analysis showed that the variable age &gt; 45 years old with OR 2,438 (p-value = 0,003; 95% CI 1,491–5,923), gender or sex with OR 0,872 (p-value 0,711; 95% CI 0,422- 1,802), family history of DM with OR 4,219 (p-value 0,003; 95% CI 1,443–4,887), obesity with OR 2,278 (p-value 0,017; 95% CI 1,152-4,503), history of hypertension with OR 2,119 (p-value 0,035; 95% CI 1,049 – 4,280), less physical activity with OR 2,412 (p-value 0,014; 95% CI 1,188-4,900) and smoking with OR 0,779 (p-value 0,541; 95% CI 0,349- 1,737). In conclusion, a family history of DM, obesity, hypertension, and lack of physical activity were significant risk factors for the incidence of type 2 diabetes mellitus in Sanjiwani Hospital, Gianyar.