Rapid Weight Loss, Central Obesity Improvement and Blood Glucose Reduction Are Associated with a Stronger Adaptive Immune Response Following COVID-19 mRNA Vaccine

Obesity is associated with a poor COVID-19 prognosis, and it seems associated with reduced humoral response to vaccination. Public health campaigns have advocated for weight loss in subjects with obesity, hoping to eliminate this risk. However, no evidence proves that weight loss leads to a better prognosis or a stronger immune response to vaccination. We aimed to investigate the impact of rapid weight loss on the adaptive immune response in subjects with morbid obesity. Twenty-one patients followed a hypocaloric, very-low-carbohydrate diet one week before to one week after the two mRNA vaccine doses. The diet’s safety and efficacy were assessed, and the adaptive humoral (anti-SARS CoV-2 S antibodies, Abs) and cell-mediated responses (IFNγ secretion on stimulation with two different SARS CoV-2 peptide mixes, IFNγ-1 and IFNγ-2) were evaluated. The patients lost ~10% of their body weight with metabolic improvement. A high baseline BMI correlated with a poor immune response (R −0.558, p = 0.013 for IFNγ-1; R −0.581, p = 0.009 for IFNγ-2; R −0.512, p = 0.018 for Abs). Furthermore, there was a correlation between weight loss and higher IFNγ-2 (R 0.471, p = 0.042), and between blood glucose reduction and higher IFNγ-1 (R 0.534, p = 0.019), maintained after weight loss and waist circumference reduction adjustment. Urate reduction correlated with higher Abs (R 0.552, p = 0.033). In conclusion, obesity is associated with a reduced adaptive response to a COVID-19 mRNA vaccine, and weight loss and metabolic improvement may reverse the effect.

Investigation of possible underlying mechanisms behind water-induced glucose reduction in adults with high copeptin

Elevated copeptin, a surrogate marker of vasopressin, is linked to low water intake and increased diabetes risk. Water supplementation in habitual low-drinkers with high copeptin significantly lowers both fasting plasma (fp) copeptin and glucose. This study aims at investigating possible underlying mechanisms. Thirty-one healthy adults with high copeptin (> 10.7 pmol·L−1 (men), > 6.1 pmol−1 (women)) and 24-h urine volume of < 1.5L and osmolality of > 600 mOsm·kg−1 were included. The intervention consisted of addition of 1.5 L water daily for 6 weeks. Fp-adrenocorticotropic hormone (ACTH), fp-cortisol, 24-h urine cortisol, fasting and 2 h (post oral glucose) insulin and glucagon were not significantly affected by the water intervention. However, decreased (Δ baseline-6 weeks) fp-copeptin was significantly associated with Δfp-ACTH (r = 0.76, p < 0.001) and Δfp-glucagon (r = 0.39, p = 0.03), respectively. When dividing our participants according to baseline copeptin, median fp-ACTH was reduced from 13.0 (interquartile range 9.2–34.5) to 7.7 (5.3–9.9) pmol L−1, p = 0.007 in the top tertile of copeptin, while no reduction was observed in the other tertiles. The glucose lowering effect from water may partly be attributable to decreased activity in the hypothalamic–pituitary–adrenal axis.ClinicalTrials.gov: NCT03574688.

Comparative free radical scavenging and hypoglycemic activities of n-hexane, ethyl-acetate, and aqueous fractions of Azanza garckeana pulp

Background: The prevalence of diabetes mellitus is increasing on a global trend. The aim of the present study is to identify the most effective antioxidants and hypoglycemic fraction of Azanza garckeana. Methods: The fractions (nhexane or ethyl-acetate or aqueous) of A. garckeana were administered to the alloxan-induced diabetic rats at doses of 100, 200, and 400 mg/kg for 15 days. Antioxidants activities were evaluated at concentrations of 62.5, 125, 250, and 500 µg/mL using the DPPH scavenging assay. Results: Results revealed that both the hexane, ethyl-acetate, and aqueous fractions exhibited hypoglycemic and antioxidants activities in a dose-dependent manner. The n-hexane fraction demonstrated highest percentage DPPH scavenging effect of 26.34±3.43, 38.44±4.35, 59.34±3.45, and 74.83±5.35 at 62.5, 125, 250, and 500 µg/mL respectively. The ethyl-acetate fraction demonstrated 19.33±2.98, 28.94±3.24, 47.34±2.90, and 57.82±4.54 respectively while the aqueous fraction exhibited the least activities of 12.45±23.45, 18.64±2.94, 27.94±3.89, and 39.43±3.89 at concentrations of 62.5, 125, 250, and 500 µg/mL respectively. In addition, the n-hexane fraction demonstrated the most significant hypoglycemic effect with the highest glucose reduction of 58.97 ±3.45 %, 63.86±5.35 %, and 66.51±4.35 %, ethyl acetate fraction demonstrated glucose reduction of 7.55±0.54%, 21.77±2.35 %, and 29.56±3.46 % while the aqueous fraction demonstrated the least hypoglycemic effect of 9.89±2.67 %, 18.09±3.45 %, and 18.87±3.24 at 100, 200 and 400 mg/kg bw respectively. Conclusion: The n-hexane fraction of Azanza garckeana extract could serve as a reservoir of bioactive agents that could be useful for the development of a new anti-diabetic agent

Chronic Antidiabetic Actions of Leptin: Evidence from Parabiosis Studies for a CNS-Derived Circulating Antidiabetic Factor

We used parabiosis to determine whether the central nervous system (CNS)-mediated antidiabetic effects of leptin are mediated by release of a brain-derived circulating factor(s). Parabiosis was surgically induced at 4 weeks of age and an intracerebroventricular (ICV) cannula was placed in the lateral cerebral ventricles at 12 weeks of age for ICV infusion of leptin or saline vehicle. Ten days after surgery, food intake, body weight and blood glucose were measured for 5 consecutive days and insulin-deficiency diabetes was induced in all rats by a single streptozotocin (STZ) injection (40 mg/kg). Five days after STZ injection, leptin or vehicle was infused ICV for 7 days, followed by 5-day recovery period. STZ increased blood glucose and food intake. Chronic ICV leptin infusion restored normoglycemia in leptin-infused rats while reducing blood glucose by ~27% in conjoined vehicle-infused rats. This glucose reduction was caused mainly by decreased hepatic gluconeogenesis. Chronic ICV leptin infusion also reduced net cumulative food intake and increased GLUT4 expression in skeletal muscle in leptin/vehicle compared to vehicle/vehicle conjoined rats. These results indicate that leptin’s CNS-mediated antidiabetic effects are mediated, in part, by release into the systemic circulation of a leptin-stimulated factor(s) that enhances glucose utilization and reduces liver gluconeogenesis.

Chronic Antidiabetic Actions of Leptin: Evidence from Parabiosis Studies for a CNS-Derived Circulating Antidiabetic Factor

We used parabiosis to determine whether the central nervous system (CNS)-mediated antidiabetic effects of leptin are mediated by release of a brain-derived circulating factor(s). Parabiosis was surgically induced at 4 weeks of age and an intracerebroventricular (ICV) cannula was placed in the lateral cerebral ventricles at 12 weeks of age for ICV infusion of leptin or saline vehicle. Ten days after surgery, food intake, body weight and blood glucose were measured for 5 consecutive days and insulin-deficiency diabetes was induced in all rats by a single streptozotocin (STZ) injection (40 mg/kg). Five days after STZ injection, leptin or vehicle was infused ICV for 7 days, followed by 5-day recovery period. STZ increased blood glucose and food intake. Chronic ICV leptin infusion restored normoglycemia in leptin-infused rats while reducing blood glucose by ~27% in conjoined vehicle-infused rats. This glucose reduction was caused mainly by decreased hepatic gluconeogenesis. Chronic ICV leptin infusion also reduced net cumulative food intake and increased GLUT4 expression in skeletal muscle in leptin/vehicle compared to vehicle/vehicle conjoined rats. These results indicate that leptin’s CNS-mediated antidiabetic effects are mediated, in part, by release into the systemic circulation of a leptin-stimulated factor(s) that enhances glucose utilization and reduces liver gluconeogenesis.

Hypoglycemic and Hepatorenal Effect of Ocimium gratissimium in Alloxan Induced Diabetic Rats

Diabetes Mellitus is a disease of public health concern which is caused by pancreatic defect in insulin secretion or failure of the receptor cells to effectively utilize secreted insulin. Diabetes account for 2-3% death in the poorest countries hence the need for alternative control measure. This stud evaluated the hypoglycemic and hepatorenal effect of Ocimium gratissimium and glibenclamide in alloxan induced diabetic rats. Twenty- four rats were randomly divided into 6 groups of 4 animals in each group (1,2,3,4,5 & 6), groups 2,3,4,5 & 6 were induced diabetes intraperitoneally with 150 mg\kg alloxan (Sigma Ltd), diabetes was confirmed by fasting blood glucose of >10.0mmol/L. Groups 3,4,5 & 6 were subsequently treated with 400 mg/kg of extract, 5mg glibenclamide, 800 mg/kg of extract, 400 mg/kg extract combined with 5mg glibenclamide respectively. Blood glucose, hepatic function variables (Aspartate aminotransferase (AST), Alanine aminotransferase(ALT), Total bilirubin (TB) and renal parameters Sodium (Na+), Potassium (K+), Urea were analyzed. The result shows an increase in glucose, hepatic and renal parameters in diabetic induced groups which was significantly reduced in a dose dependent manner in the diabetic treated groups, the high dose of the extract (800mg/kg) was more effective in blood glucose reduction than the standard antidiabetic drug, (5mg glibenclamide). However, 5mg glibenclamide was found to be more effective in blood glucose reduction than the low dose (400mg/kg) extract, the combination of 5mg glibenclamide and 400mg/kg was found to be more effective in blood glucose reduction than the low dose extract. A significant increase was observed in the Total bilirubin and urea parameters of the high dose (800mg/kg) of the extract treated groups and in the combined group (400 mg/kg+5 mg glibenclamide). When compared to the low dose extract group(400mg/kg). Low dose ocimium gratissimium potentiates 5mg glibenclamide in blood glucose reduction. Ocimium gratissimium and glibenclamide decreased blood glucose and ameliorates alloxan induced hepatic and renal damage. The use of the high dose of the extract and the use of the combination of the drug (5mg glibenclamide) and the low dose of the extract in diabetes management may be detrimental to the liver and kidney according to this study.

Synergies of herbal teas on improved plasma antioxidant capacity and postprandial hypoglycemic response in healthy adults

Herbal teas play a major role in the global traditional food cultures. There are a variety of herbal teas used for general wellness and prevention and management of chronic diseases including diabetes mellitus. The present study aimed to determine the phenolic content and antioxidant activities of herbal teas prepared with matured jackfruit (Artocarpus heterophyllus) leaves after senescence and abscission, and dried Cassia (Cassia auriculata) flowers and buds. The sensory evaluation was performed using 50 untrained panelists to determine the amount of herbal ingredient to be used in the preparation of herbal tea. Furthermore, the potential single dose efficacy of three herbal teas, namely, Jackfruit leaves tea (JLT), Cassia flower tea (CFT) and mixed jackfruit leaves and Cassia flower tea (JCT) on postprandial glycemic response and plasma antioxidant capacity (PAC) of healthy adults were investigated. Phenolics were identified using high performance liquid chromatography–tandem mass spectrometry. A randomized crossover study was led with 16 healthy adults who consumed 250 mL of freshly prepared herbal beverage with 50 g glucose and 50 g glucose in 250 mL water as the control randomly within three visits with a washout period of four days between two visits. Blood samples were collected using microcapillary tubes at the baseline and postprandial at 30, 45, 60, 90, and 120 min. The plasma was analyzed for glucose concentration (PGC) and PAC. JLT and JCT showed a significant reduction of PGC compared to the control at 30, 45, and 60 min time points. JLT and JCT showed higher efficacy in plasma glucose reduction than CFT. All herbal teas significantly increased PAC at the end of 120 min post ingestion. Further research is warranted to examine the synergistic effect of two mixed ingredients for herbal tea and the long-term efficacy of multiple dose ingestion of respective herbal teas in the prevention and management of hyperglycemia and type 2 diabetes.

Cardiovascular outcomes of antidiabetic drugs

Type 2 Diabetes Mellitus (T2DM) is associated with a high risk of atherosclerotic cardiovascular disease (ASCVD). Intensive blood glucose reduction with antidiabetic drugs significantly reduce microvascular complications but there is no strong evidence of reduction in cardiovascular (CV) events. In 2008, the US Food and Drug Administration (FDA) issued guidance to demonstrate cardiovascular safety of newer antidiabetic drugs in addition to reduction in blood glucose level. After which a number of CVOTs were conducted involving newer antidiabetic drugs. The newer drugs (e.g. GLP-1 RAs, SGLT2 inhibitors and DPP 4 inhibitors) might have potential effects on body weight, lipid parameters and blood pressure, as well as endothelial dysfunctions, inflammatory markers and oxidative stress. The current review summarizes the results of the main trials focused on the cardiovascular outcomes of traditional as well as newer antidiabetic drugs.

Cost-Effectiveness Analysis of Type 2 Diabetes Mellitus (T2DM) Treatment in Patients with Complications of Kidney and Peripheral Vascular Diseases in Indonesia

Type 2 diabetes mellitus (T2DM) is a chronic disease with high-cost treatment. This study aimed to analyze the cost-effectiveness of T2DM treatment in hospitalized patients with complications of kidney and peripheral vascular disease (PVD) in Indonesia by focusing on patients of Health Social Security Agency (BPJS Kesehatan). An observational study was applied by collecting data retrospectively from patients’ medical record at the biggest public hospital in West Java Province, Indonesia. Two perspectives of payer and healthcare provider were applied to estimate the treatment cost. We considered following inclusion criteria: (i) Hospitalized T2DM patients without complication, with complications of kidney and PVD during 2014–2017; (ii) member of BPJS Kesehatan; (iii) >18 years old patients; and (iv) patients with complete medical record data. The results showed that the majority patients were female (56.72%), 45–64 years old (69.40%), and had a length of stay at 4–10 days (54.48%). The greatest contributions in the total treatment cost were found to be hospital room, medical services and medicines for the treatment of T2DM without complications, with complications of kidney and PVD, respectively. From the perspective of payer, the incremental cost-effectiveness ratios (ICERs) of T2DM treatment with complications of kidney and PVD would be IDR 215,723 and IDR 234,591 per 1 mg/dL blood glucose reduction, respectively. From the perspective of healthcare provider, the ICERs of T2DM treatment with complications of kidney and PVD would be IDR 166,289 and IDR 681,853 per 1 mg/dL blood glucose reduction in both perspectives (1 US$ = IDR 13,451). In a comparison with T2DM without complication, reducing 1 mg/dL blood glucose in T2DM treatment with complication of PVD would require higher cost than in T2DM treatment with complication of kidney from both perspectives.