Decline In Blood Glucose Research Articles

Therapeutic Potential of Fecal Microbiota Transplantation in Type 2 Diabetes Mellitus: A Systematic Review.

Diabetes mellitus is a chronic metabolic disease characterized by insulin resistance and hyperglycemia. It can cause various complications, which result in significant morbidity and mortality. There are multiple treatment options available to combat this disease; however, despite this, the incidence of type 2 diabetes mellitus is continuously increasing. Some promising results have shown that dysbiosis has a role in the pathogenesis of type 2 diabetes mellitus and fecal microbiota transplantation (FMT) in animals; however, the usage of FMT in humans needs further clarification and review. We explored PubMed, Popline, and Cochrane Library to identify relevant papers. Eight articles were then finalized after screening and applying eligibility criteria. These articles explored the role of the therapeutic efficacy of FMT in insulin resistance and hyperglycemia. The studies showed that the FMT had a positive impact on managing hyperglycemia and insulin resistance, which is evident in the decline of blood glucose and HBA1c levels and the rise of insulin and C-peptides. In addition, FMT also helped to control other risk factors such as hyperlipidemia and blood pressure; however, the impact on weight loss is not convincing. FMT also influenced the levels of some microbiota, which could be involved in controlling hyperglycemia and insulin resistance. Due to limited control trials and study periods and the small sample size of diabetic patients, more research is needed to explore the impact of FMT in controlling type 2 diabetes mellitus.

Investigation of Factors Influencing the Effectiveness of Deformable Nanovesicles for Insulin Nebulization Inhalation.

Nebulized inhalation offers a noninvasive method for delivering drugs to treat both local respiratory and systemic diseases. In this study, insulin was used as a model drug to design a series of deformable nanovesicles (DNVs) with key quality attributes, including particle size, deformability, and drug load capacity. We investigated the effects of these properties on aerosol generation, macrophage phagocytosis, and bloodstream penetration. The results showed that deformability improved nebulization performance and reduced macrophage phagocytosis, benefiting local and systemic delivery. However, the advantage of DNVs for transmembrane penetration was not evident in the alveolar epithelium. Within the size range of 80-490 nm, the smaller the particle size of IPC-DNVs, the easier it is to evade clearance by macrophages and the more effective the in vivo hypoglycemic efficacy will be. In the drug load range of 3-5 mg/mL, a lower drug load resulted in better hypoglycemic efficacy. The area above the blood glucose decline curve with time (AAC) of nebulized DNVs was 2.32 times higher than that of the insulin solution, demonstrating the feasibility and advantages of DNVs in the pulmonary delivery of biomacromolecule drugs. This study provides insights into the construction and formulation optimization of pulmonary delivery carriers.

Glycemic Management Around Postprandial Exercise in People With Type 1 Diabetes: Challenge Accepted.

The precise glycemic impact and clinical relevance of postprandial exercise in type 1 diabetes (T1D) has not been clarified yet. This work aimed to examine acute, subacute, and late effects of postprandial exercise on blood glucose (BG). A randomized, controlled trial comprised 4 laboratory visits, with 24-hour follow-up at home. Participants included adults with T1D (n = 8), aged 44 ± 13 years, with body mass index of 24 ± 2.1. Intervention included 30 minutes of rest (CONTROL), walking (WALK), moderate-intensity (MOD), or intermittent high-intensity (IHE) exercise performed 60 minutes after a standardized meal. Main outcome measures included BG change during exercise/control (acute), and secondary outcomes included the subacute (≤2 h after) and late glycemic effects (≤24 h after). Exercise reduced postprandial glucose (PPG) excursion compared to CONTROL, with a consistent BG decline in all patients for all modalities (mean declines -45 ± 24, -71 ± 39, and -35 ± 21 mg/dL, during WALK, MOD, and IHE, respectively (P < .001). For this decline, clinical superiority was demonstrated separately for each exercise modality vs CONTROL. Noninferiority of WALK vs MOD was not demonstrated, noninferiority of WALK vs IHE was demonstrated, and equivalence of IHE vs MOD was not demonstrated. Hypoglycemia did not occur during exercise. BG increased in the hour after exercise (more than after CONTROL; P < .001). More than half of participants showed hyperglycemia after exercise necessitating insulin correction. There were more nocturnal hypoglycemic events after exercise vs CONTROL (P < .05). Postprandial exercise of all modalities is effective, safe, and feasible if necessary precautions are taken (ie, prandial insulin reductions), as exercise lowered maximal PPG excursion and caused a consistent and clinically relevant BG decline during exercise while there was no hypoglycemia during or shortly after exercise. However, there seem to be 2 remaining challenges: subacute postexercise hyperglycemia and nocturnal hypoglycemia.

Construction of a 10rolGLP-1-expressing glucose-lowing Saccharomyces cerevisiae by CRISPR/Cas9 technique

To develop a novel glucose-lowering biomedicine with potential benefits in the treatment of type 2 diabetes, we used the 10rolGLP-1 gene previously constructed in our laboratory and the CRISPR/Cas9 genome editing technique to create an engineered Saccharomyces cerevisiae strain. The gRNA expression vector pYES2-gRNA, the donor vector pNK1-L-PGK-10rolGLP-1-R and the Cas9 expression vector pGADT7-Cas9 were constructed and co-transformed into S. cerevisiae INVSc1 strain, with the PGK-10rolGLP-1 expressing unit specifically knocked in through homologous recombination. Finally, an S. cerevisiae strain highly expressing the 10rolGLP-1 with glucose-lowering activity was obtained. SDS-PAGE and Western blotting results confirmed that two recombinant strains of S. cerevisiae stably expressed the 10rolGLP-1 and exhibited the desired glucose-lowering property when orally administered to mice. Hypoglycemic experiment results showed that the recombinant hypoglycemic S. cerevisiae strain offered a highly hypoglycemic effect on the diabetic mouse model, and the blood glucose decline was adagio, which can avoid the dangerous consequences caused by rapid decline in blood glucose. Moreover, the body weight and other symptoms such as polyuria also improved significantly, indicating that the orally hypoglycemic S. cerevisiae strain that we constructed may develop into an effective, safe, economic, practical and ideal functional food for type 2 diabetes mellitus treatment.

Arene‐Ruthenium(II)/Osmium(II) Complexes Potentiate the Anticancer Efficacy of Metformin via Glucose Metabolism Reprogramming

AbstractTargeting metabolic reprogramming to treat cancer could increase overall survival and reduce side effects. Here, we put forward a strategy using arene‐ruthenium(II)/osmium(II) complexes to potentiate the anticancer effect of metformin (Met.) via glucose metabolism reprogramming. Complexes 1–6 with oxoglaucine derivatives as ligands were synthesized and their anti‐tumor activities were tested under hypoglycemia. Results indicated that 2 and 5 potentiated the anticancer effects of Met. under hypoglycemia, exhibiting lower toxicity, slower blood glucose decline and inhibition of early tumor liver metastasis. Combination of 5 with Met. could be used as a new strategy to treat cancer under hypoglycemia through glucose metabolism reprogramming.

Arene-Ruthenium(II)/Osmium(II) Complexes Potentiate the Anticancer Efficacy of Metformin via Glucose Metabolism Reprogramming.

Targeting metabolic reprogramming to treat cancer could increase overall survival and reduce side effects. Here, we put forward a strategy using arene-ruthenium(II)/osmium(II) complexes to potentiate the anticancer effect of metformin (Met.) via glucose metabolism reprogramming. Complexes 1-6 with oxoglaucine derivatives as ligands were synthesized and their anti-tumor activities were tested under hypoglycemia. Results indicated that 2 and 5 potentiated the anticancer effects of Met. under hypoglycemia, exhibiting lower toxicity, slower blood glucose decline and inhibition of early tumor liver metastasis. Combination of 5 with Met. could be used as a new strategy to treat cancer under hypoglycemia through glucose metabolism reprogramming.

Taurine supplementation enhances endurance capacity by delaying blood glucose decline during prolonged exercise in rats

Taurine enhances physical performance; however, the underlying mechanism remains unclear. This study examined the effect of taurine on the overtime dynamics of blood glucose concentration (BGC) during endurance exercise in rats. Male F344 rats were subjected to transient treadmill exercise until exhaustion following 3 weeks of taurine supplementation or non-supplementation (TAU and CON groups). Every 10 min during exercise, BGC was measured in blood collected through cannulation of the jugular vein. Gluconeogenesis-, lipolysis-, and fatty acid oxidation-related factors in the plasma, liver, and skeletal muscles were also analyzed after 120-min run. Exercise time to exhaustion was significantly longer with taurine supplementation. BGC in the two groups significantly increased by 40 min and gradually and significantly decreased toward the respective exhaustion point. The decline in BGC from the peak at 40 min was significantly slower in the TAU group. The time when the once-increased BGC regressed to the 0-time level was significantly and positively correlated with exercise time until exhaustion. At the 120-min point, where the difference in BGC between the two groups was most significant, plasma free fatty acid concentration and acetyl-carnitine and N-acetyltaurine concentrations in skeletal muscle were significantly higher in the TAU group, whereas glycogen and glucogenic amino acid concentrations and G6Pase activity in the liver were not different between the two groups. Taurine supplementation enhances endurance capacity by delaying the decrease in BGC toward exhaustion through increases of lipolysis in adipose tissues and fatty acid oxidation in skeletal muscles during endurance exercise.

Efficacy and Safety of Low Dose Insulin Infusion against Standard Dose Insulin Infusion in Children with Diabetic Ketoacidosis- An Open Labelled Randomized Controlled Trial.

Objective:To compare the efficacy and safety of low dose insulin infusion (0.05 U/kg/h) against the standard dose insulin infusion (0.1 U/kg/h) in children with diabetic ketoacidosis.Method:Children (age <12 years, n = 30) presenting with diabetic ketoacidosis were enrolled and randomised to receive insulin infusion either as 0.05 U/kg/h (low dose) or 0.1 U/kg/h (standard dose) as an open labelled randomised controlled trial. The rest of the management was identical in both groups. The time taken for resolution of acidosis (pH ≥7.3 and HCO3 ≥15) was the primary outcome variable. The secondary outcome variables included the time taken until a decline in blood glucose to 250 mg/dl, the proportion of children developing hypoglycemia and hypokalemia, and any treatment failure.Results:The two groups were similar with respect to mean age, weight and gender distribution. New-onset diabetes was diagnosed on 24/30. The mean ± SD time for resolution of acidosis was similar between the groups; 27.0 ± 6.1 hours in the low dose group vs 23.4 ± 7.3 hours in standard dose group, P = 0.16. The mean time for the decline in blood glucose to 250 mg/dl was 13.0 ± 5.9 hours in low dose vs 11.6 ± 6.0 hours in standard dose group, P = 0.52. A lesser proportion of participants developed hypoglycemia and hypokalemia in the low dose group, though not statistically significant. There was no incidence of treatment failure in either group.Conclusion:Low dose insulin infusion is equally effective and safe as standard dose insulin infusion in children with diabetic ketoacidosis.

Histopathological Profiles of Rats (Rattus norvegicus) Induced with Streptozotocin and Treated with Aqueous Root Extracts of Ruellia tuberosa L.

Diabetes mellitus (DM) is a serious worldwide health threat since the number of people with DM is forecasted to grow annually. Thus, effective and affordable treatment is urgently needed. Our previous studies used n-hexane and hydroethanolic root extracts of Ruellia tuberosa L. which significantly affected diabetic rats. In this study, aqueous R. tuberosa L. root extracts were used as treatments for the diabetic rat model and their effects were evaluated. Diabetes was generated by the administration of streptozotocin (STZ) at 20 mg/kg within 5 sequential days. Male Wistar rats were orally treated with the extracts and standard drug (metformin 200 mg/kg) and vehicle every day for 4 weeks. Hypoglycemic effects were assessed for normal, diabetic control, standard, and extract-treated groups. Histopathology was also carried out for the pancreatic, hepatic, and kidney tissues. The progression of diabetes was considerably diminished after extract treatment. In treated rats, the highest dose of extract induced a decline in blood glucose and serum malondialdehyde (MDA) levels at 25% and 35%, respectively. Furthermore, aqueous extract of R. tuberosa L. treatment decreased MDA levels in the pancreas by 12%. Histologic examination of the organ tissues of diabetic rats showed deteriorating alterations. After treatment, histopathological damages to the tissues and cells were reversed. The results of the experiments recommend that aqueous extract of R. tuberosa L. has antidiabetic effects on STZ-induced diabetic rats; nevertheless, a higher dose of the aqueous extracts is needed to achieve more significant results.

Evaluation of Mesoporous Silica Nanoparticles as Delivery Vehicles for Novel Hybrid Steroids in Management of Metabolic Syndrome in Mice

This approach aimed to address the efficacy of the newly synthesized hybrid steroids modified by sulfurheterogenous rings and loaded on mesoporous silica nanoparticles in manipulating metabolic syndrome induced by high fructose diet. The designed compounds were synthesized by mechanochemical process and then loaded on mesoporous silica nanoparticles as drug delivery vehicles. Thereafter, these compounds were examined for counteracting metabolic syndrome inmice. The synthesized compounds revealed potentiality to prevent body weight gain as indicated by the decreased BMI of the mice fed high fructose diet. The hypolipidemic effect of the designed compounds was evidenced by the reduction of serum cholesterol, triglycerides, LDL-cholesterol and the enhancement of HDL-cholesterol levels. Moreover, the compounds displayed a significant decline in blood glucose and insulin levels. So, they exhibited significant betterment in insulin resistance of the treated mice. Furthermore, the treatment with these compounds improved serum spexin level in metabolic syndrome-challenged mice. Ultimately, the tested compounds demonstrated powerful free radical scavenging activity manifested by lowering MDA, NO and H2O2 serum levels. Conclusively, the newly modified hybrid steroid compounds proved good performance against metabolic syndrome in mice most probably due to their content of sulfur atom, in addition to their loading on mesoporous silica nanoparticles.

Effect of Six Months Yoga Intervention on Metabolic Profile and Carotid Intima Media Thickness in Prediabetes

Introduction: Diabetes, the most common endocrine disorder, is projected to show a worldwide increase from 366 million people in the year 2011 to 552 million in the year 2030, out of which around 101 million is expected to be contributed by India. Moreover, the disease manifestations start in the early stages of diabetes and before it gets established as a full blown condition in the pre-stage called prediabetes. Aim: To highlight the importance of yoga intervention on metabolic profile and Carotid Intima Media Thickness (CIMT) in prediabetic subjects and implement it as a therapy for primary prevention of diabetes. Materials and Methods: This interventional study was done among adults aged 31-50 years in RUHS College of Medical Sciences and Associated Rukmani Devi Beni Prasad Jaipuria Hospital in Jaipur City, Rajasthan, India. A total of 250 prediabetic subjects were recruited from Jaipuria Hospital. These were divided into two groups, Study group (Group A, n=125) were engaged in yoga session and Control group (Group B, n=125) did not perform any yoga session. Written informed consent was taken from the participants in the local language. Study was conducted over a period of six months from July to December 2018. Statistical analysis was done by student’s paired t-test for intragroup comparison before applying this test the Smirnov-Kolmogorov test was conducted to confirm the normality of each parameter. Results: Yoga intervention resulted in a significant decline in blood glucose (p&lt;0.0001), Glycated haemoglobin (p&lt;0.01), lipid profile Cholesterol (p&lt;0.01), Triglyceride (p&lt;0.01), Low Density Lipoprotein (LDL) (p&lt;0.01), High Density Lipoprotein (HDL) (p-value &gt;0.05) and Very Low Density Lipoprotein (VLDL) (p-value &gt;0.05), CIMT (p-value &lt;0.05) relative to the control group. Conclusion: Yoga intervention was found to be helpful in control of metabolic profile and CIMT in prediabetes subjects. This preliminary study indicates that a yoga intervention would be a possible risk reduction option for adults at high risk for type 2 diabetes. In addition, yoga holds promise as an approach in reducing cardiometabolic risk factors, atherosclerosis and Cardiovascular (CV) events.

Potential of peel extracts of Punica granatum and Citrus aurantifolia on alloxan-induced diabetic rats

BackgroundPeel is one of the major by-products in fruit processing industry. Fruit products (non-edible parts) are also considered as waste products and often discarded in the environment. Fruit peels are now serving as one of the primary sources for isolation and extraction of secondary metabolites in pharmaceutical industry. The present investigation was carried out to screen the phytochemical constituents and HPTLC analysis of peel extracts of Punica granatum and Citrus aurantifolia and their antidiabetic potential in alloxan-induced diabetic rats.ResultsAmong the different solvent extracts, methanol solvent extract was found to possess more amounts of secondary metabolites. In addition, HPTLC analysis of the plant samples revealed the presence of 13 peaks in both the plants by using gallic acid as marker. Different biochemical parameters such as blood glucose, cholesterol, protein, urea, creatinine, and triglycerides level were subjected for estimation by collecting the blood samples from the treated diabetic rats after 21 days. A sharp decline in blood glucose, cholesterol, triglycerides, creatinine, and urea level was noticed when methanolic extracts of Punica granatum and Citrus aurantifolia were given to experimental animals when compared with negative control. However, protein and weight of the animal were found to be enhanced when treated with methanolic extracts of both the plants.ConclusionIt can be concluded that fruit peels of both the plants exhibited antidiabetic potential on alloxan-induced diabetic rats which can be attributed to wide range of active pool of secondary metabolites. Further, screening and isolation of secondary metabolites along with their mode of action is required for effective use of plant-based drugs as antihyperglycemic agent.Graphical abstract

24-OR: Electronic Decision Support for Insulin Therapy Is Safe and Efficient in Inpatients with Type 2 Diabetes

Attainment of good glycemic control in hospitalized patients with type 2 diabetes (T2D) is often hampered by fear of hypoglycemia and insufficient knowledge in insulin therapy. An electronic algorithm-based decision support system (GlucoTab®, decide Clinical Software GmbH, Graz, Austria) for inpatient management was developed and has proven efficacy in clinical trials. After implementing GlucoTab® in routine care, a retrospective analysis of T2D patients requiring subcutaneous insulin therapy on an Endocrinology ward was performed. Data from days when patients received algorithm-steered basal-bolus insulin therapy (BBI) was compared with days when insulin therapy was performed according to local standard care (SC) provided by an endocrinologist. As the treating physician was free to start/stop decision support during inpatient stay, patients switched between BBI and SC. During the first six months following GlucoTab® implementation, a total of 71 T2D patients required subcutaneous insulin therapy and subsequently were included in this analysis. Incomplete treatment days (e.g., admission and discharge days; days, where both therapy schemes applied) were excluded, resulting in 261 BBI and 274 SC days. Baseline characteristics were as follows: 39 % women, 99 % Caucasian, age 73.5 ± 12.5 years, diabetes duration 15.4 ± 10.6 years, HbA1c 70.4 ± 24.2 mmol/mol, BMI 29.0 ± 5.5 kg/m² and creatinine 1.6 ± 1.2 mg/dL. Mean daily glucose was lower for BBI vs. SC: 156.9 ± 35.7 mg/dL vs. 172.1 ± 47.3 mg/dL. Total daily insulin dose was higher for BBI vs. SC: 42.2 ± 25.2 U vs. 33.7 ± 20.9 U. Blood glucose (BG) in target (70-180 mg/dL) was higher for BBI vs. SC: 70 % vs. 61.2 %. BG &amp;lt;70 mg/dL was 1.6 % vs. 1.9 % and BG &amp;lt;54 mg/dL was 0.2 % vs. 0.6 % (BBI vs. SC, respectively). Continuous use of BBI resulted in a BG decline from 182 (day 1) to 147 mg/dL (day 10) while it remained elevated in SC (188 to 177 mg/dL). BBI showed beneficial glycemic control compared to SC in routine use during inpatient diabetes management. Disclosure D.A. Hochfellner: None. H. Ziko: None. M.H. Sagmeister: None. H. Elsayed: None. M. Cigler: None. T. Poettler: None. F. Aberer: None. G. Sendlhofer: None. P. Beck: Employee; Self; decide Clinical Software. Stock/Shareholder; Self; decide Clinical Software. J.K. Mader: Advisory Panel; Self; Becton, Dickinson and Company, Eli Lilly and Company, Medtronic, Prediktor Medical, Sanofi-Aventis. Speaker’s Bureau; Self; Abbott, Eli Lilly and Company, Medtronic, Novo Nordisk A/S, Roche Diabetes Care, Sanofi-Aventis.

Effects of millet based functional foods rich diet on coronary risk factors among subjects with diabetes mellitus: a single arm real world observation from hospital registry

Introduction: Diabetes mellitus has become a global public health problem, characterized by increased intake of western style diets and decline in physical activities which are pro-inflammatory. Food diversity, nutrient profile, glycemic index and lower content of salt sugar and Tran’s fat are an important consideration for a healthy anti-inflammatory diet which may be advised for prevention of diabetes mellitus and cardiovascular diseases (CVDs). This clinical observation aims to examine the effects of a millets based functional food rich intervention diet on coronary risk factors among subjects with known diabetes. Method: After permission from the review board of a hospital, hospital records of 65 subjects with type 2 diabetes mellitus were drawn for this study. Of 65 patients with diabetes, 5 were excluded and remaining 60 were administered millet-based functional food rich intervention diet (millets 60%, soya bean 20%, brown rice 10%, peanuts 8% and flex seeds 2%). Clinical data, dietary intakes and physical activity were assessed by validated questionnaires. Blood pressures were measured by sphygmomanometer. Result: Treatment with millet based intervention diet for 12 weeks was associated with a significant decline in fasting and 2-hour postprandial blood glucose, HbA1c indicating that this diet can prevent diabetes. Total cholesterol, VLDL cholesterol and triglycerides showed a significant decline compared to baseline levels. Pro-inflammatory cytokines; C-reactive proteins, TNF-alpha and interleukin-6 also showed significant reduction after treatment with intervention diet compared to baseline levels. In association with these changes, there was a significant decline in systolic and diastolic blood pressures, parameters of oxidative stress; TBARS, MDA and diene conjugates with an increase in antioxidant vitamins; A,E and C and beta-carotene. Underlying these changes, all subjects received an 11 fold greater amount of millet-based intervention diet which increased from mean 21.36±3.8g/day to 235.20±23.6 (p&lt;0001).Among females (n=33), there was a significant increase in hemoglobin and serum calcium and magnesium indicating that millet based diet can also prevent under nutrition. Conclusion: It is possible that millet-based intervention diet can cause a significant decline in blood glucose, HbA1c, oxidative stress, blood pressures, blood lipoproteins and pro-inflammatory cytokines with an increase in antioxidant vitamins, magnesium, calcium and hemoglobin. Randomized, controlled intervention trials, would be necessary to confirm our findings.

&lt;p&gt;2-dodecyl-6-methoxycyclohexa-2,5-diene-1,4-dione isolated from &lt;em&gt;Averrhoa carambola L&lt;/em&gt;. root ameliorates diabetic nephropathy by inhibiting the TLR4/MyD88/NF-κB pathway&lt;/p&gt;

BackgroundAverrhoa carambola L. is a traditional medicinal herb that has long been used to treat diabetes. Our previous studies found that 2-dodecyl-6-methoxycyclohexa-2,5-diene-1,4-dione (DMDD) isolated from A. carambola L. roots could ameliorate diabetic nephropathy (DN), but its exact mechanism remains unclear.MethodsA DN model was established by streptozotocin (STZ, 100 mg/kg body weight) in TLR4 knockout (TLR4-/-, KO) mice and wild-type (WT) mice. Body weight and blood glucose were evaluated after oral administration of DMDD (12.5, 25, 50 mg/kg body weight/d) in diabetic mice. The levels of serum lipids, including TC, TG, HDL, and LDL and kidney function indexes Scr and BUN, were detected by biochemical equipment. The levels of inflammatory cytokines including IL-6 and TNF-α, were determined by ELISA kits. Furthermore, changes in renal ultrastructure were observed by electron microscopy. Western blot analysis and RT-PCR were used to assess the protein expression and mRNA levels of TLR4, MyD88 and NF-κB.ResultsDMDD treatment attenuated diabetic nephropathy, as a result of a decline in blood glucose, serum creatinine, and blood urine nitrogen levels and an increase in the quantity and density of podocytes, combined with improved dyslipidaemia. DMDD treatment inhibited the inflammatory response and downregulated the expression of the TLR4/MyD88/NF-κB pathway in diabetic mice, and these changes were significantly different in TLR4-/- mice.ConclusionDMDD alleviates diabetic nephropathy by mitigating kidney damage and inflammation via the inhibition of the TLR4/MyD88/NF-κB signalling pathway.

Hindbrain estrogen receptor regulation of ventromedial hypothalamic glycogen metabolism and glucoregulatory transmitter expression in the hypoglycemic male rat

Estrogen receptor-alpha (ERα) and -beta (ERβ) occur in key elements of the brain gluco-homeostatic network in both sexes, including the hindbrain dorsal vagal complex (DVC), but the influence of distinct receptor populations on this critical function is unclear. The ventromedial hypothalamic nucleus (VMN) maintains glucose balance by integrating nutrient, endocrine, and neurochemical cues, including metabolic sensory information supplied by DVC A2 noradrenergic neurons. Current research utilized the selective ERα and ERβ antagonists MPP and PHTPP to characterize effects of DVC ERs on VMN norepinephrine (NE) activity and metabolic neurotransmitter signaling in insulin-induced hypoglycemic (IIH) male rats. Data show that ERβ inhibits VMN glycogen synthase and stimulates phosphorylase protein expression, while attenuating hypoglycemic augmentation of glycogen content. Furthermore, both ERs attenuate VMN glucose concentrations during IIH. Hypoglycemic up-regulation of nitric oxide (NO) and brain-derived neurotrophic factor (BDNF) signaling was correspondingly driven by ERα or -β, whereas GABA and steroidogenic factor-1 were respectively suppressed independently of ER input or by ERβ. IIH intensified VMN NE accumulation by ERβ-dependent mechanisms, but did not alter NE levels in other gluco-regulatory loci. ERβ amplified the magnitude of insulin-induced decline in blood glucose. Both ERs regulate corticosterone, but not glucagon secretion during IIH and oppose hypoglycemic diminution of circulating free fatty acids. These findings identify distinguishing versus common VMN functions targeted by DVC ERα and -β. Sex differences in hypoglycemic VMN NE accumulation, glycogen metabolism, and transmitter signaling may involve, in part, discrepant regulatory involvement or differential magnitude of impact of these hindbrain ERs.

High-Intensity Interval Training Improves Aerobic Capacity Without a Detrimental Decline in Blood Glucose in People With Type 1 Diabetes.

We investigated whether 6 weeks of high-intensity interval training (HIT) induced improvements in cardiometabolic health markers similar to moderate-intensity continuous training (MICT) in people with type 1 diabetes (T1D), and whether HIT abolished acute reductions in plasma glucose levels observed after MICT sessions. Two groups of sedentary individuals with T1D (n = 7 per group) completed 6 weeks of thrice weekly HIT or MICT. Pre- and post-training measurements were made of 24-hour interstitial glucose profiles, using continuous glucose monitors, and cardiometabolic health markers [peak oxygen consumption (V˙o2peak), blood lipid profile, and aortic pulse wave velocity (aPWV)]. Capillary blood glucose (BG) concentrations were assessed before and after exercise to investigate changes in BG levels during exercise in the fed state. Six weeks of HIT or MICT increased V˙o2peak by 14% and 15%, respectively (P < 0.001), and aPWV by 12% (P < 0.001), with no difference between groups. There was no difference in incidence or percentage of time spent in hypoglycemia after training in either group (P > 0.05). In the fed state, the mean change (±SEM) in capillary BG concentration during the HIT sessions was -0.2 ± 0.5 mmol/L, and -5.5 ± 0.4 mmol/L during MICT. Six weeks of HIT improved V˙o2peak and aPWV to a similar extent as MICT. That BG levels remained stable during HIT in the fed state but consistently fell during MICT suggests HIT may be the preferred training mode for some people with T1D.

Exercise modes and their association with hypoglycemia episodes in adults with type 1 diabetes mellitus: a systematic review

ObjectiveType 1 diabetes mellitus rates are rising worldwide. The health benefits of physical exercise in this condition are many, but more than 60% do not participate, mainly from fear of...

Brain-derived neurotrophic factor, insulin like growth factor-1 and inflammatory cytokine responses to continuous and intermittent exercise in patients with type 1 diabetes

AimsType 1 diabetes mellitus (T1DM) is an important risk factor for cognitive decline and motor dysfunction due to progressive muscular atrophy. Chronic hyperglycemia may be responsible for impaired vascular function, loss of muscle mass, and morphological abnormalities in the myocytes. For the proper functioning of the neuromuscular system, two crucial growth factors are necessary: brain-derived neurotrophic factor (BDNF) and insulin-like growth factor-1 (IGF-1), whose reduced expressions have been implicated in progressive neuropathy and muscle atrophy in patients with T1DM.The aim of the study was to compare the effects of two different exercise regimes (continuous and intermittent) on BDNF, IGF-1, blood glucose and inflammatory cytokine responses in young adults with and without Type 1 diabetes. MethodsFourteen patients (aged: 26.9 years) with T1DM and age-matched adults without diabetes participated in a 40 min continuous exercise (ExC, 50% of lactate threshold) and a high intensity intermittent exercise (ExInt, 120% of lactate threshold). During the study the patients performed self-monitoring of blood glucose levels (SMBG) under glycemic control. The effects of ExC and ExInt on BDNF, IGF-1, insulin like growth factor binding protein (IGFBP-3), insulin (INS), vascular endothelial growth factor (VEGF), transforming growth factor beta (TGF-β) and tumor necrosis factor alpha (TNF-α) were analyzed. ResultsBDNF and IGF-1 baseline serum levels were significantly lower in the T1DM patients compared to the healthy controls, but we found that ExInt and ExC significantly increase the secretion of BDNF and IGF-1 levels. Significant increases in BDNF and TGF-β levels, higher blood glucose decline, and a lower incidence of hypoglycaemia in ExInt compared to ExC were observed. Lower IGFBP-3 concentrations were revealed in T1DM patients in response to ExInt compared to ExC, suggesting a positive effect on IGF-1/IGFBP-3 ratio and the bioavailability of IGF-1. ConclusionsAccording to our results physical exercise has beneficial effects on serum BDNF and IGF-1 levels. A high-intensity intermittent exercise may be more effective at reducing the risk of exercise-induced glycaemic disorders in the T1DM patients as compared to continuous exercise.

The Acute Effects of Exercise Intensity on Blood Glucose Levels in Type 1 Diabetics

For individuals with Type 1 diabetes mellitus (T1DM), regular physical activity is a fundamental strategy in the management of glycemic control. Previous studies have shown that continuous, moderate-intensity exercise in individuals with T1DM decreases blood glucose concentrations, often resulting in hypoglycemia, whereas vigorous-intensity exercise can increase blood glucose, impacting the risk of hyperglycemia. Sprint interval training (SIT), characterized by brief, all-out bursts of supramaximal exercise, has been shown to improve indices of cardiometabolic health, despite a minimal time commitment. However, the effects of low volume SIT on individuals with T1DM is largely unknown. PURPOSE: to contrast the acute effects of exercise intensity on blood glucose levels in Type 1 diabetics. METHODS: Four recreationally active college- age students with T1DM, completed a treadmill test to determine maximal aerobic speed (MAS), and performed each of the following 20-min treadmill-based protocols: 1) Moderate-intensity continuous training (MICT): 5-min warm-up (WU), 10 minutes at 70% MAS, 5-min cool-down (CD); 2) high-intensity interval training (HIIT): 5-min WU, 1-min at 90% MAS, 1-min at 30% MAS repeated 5 times, 5-min CD; 3) SIT: 5-min WU, 30-sec at 120% MAS, 2-min, 50-sec at 30% MAS repeated 3 times, 5-min CD. Blood glucose was monitored via glucometer every 5-min during exercise and for 45-min after. RESULTS: A statistically significant decline in blood glucose was observed in both the MICT and HIIT conditions (p <0.001, respectively) but not in the SIT condition (p = 0.696). From baseline to the 45-min mark, blood glucose decreased by 27% in both the MICT (180 ± 27 to 132 ± 39) and HIIT (183 ± 29 to 132 ± 15) protocols, but only 11% in the SIT (193 ± 41 to 165 ± 70) protocol. CONCLUSIONS: The results of this study provide initial proof-of-concept that a low volume SIT protocol can maintain target blood glucose levels while exercising in individuals with T1DM.