Metformin ameliorates neuronal necroptosis after intracerebral hemorrhage by activating AMPK

2021 ◽  
Vol 18 ◽  
Author(s):  
Chenhan Lin ◽  
Kaichuang Yang ◽  
Guoqiang Zhang ◽  
Jun Yu
Keyword(s):  
Type 2 Diabetes ◽  
Cell Death ◽  
Intracerebral Hemorrhage ◽  
Neurological Function ◽  
Future Research ◽  
Secondary Injury ◽  
First Line ◽  
New Perspective ◽  
Related Pathway

Background: Intracerebral hemorrhage (ICH) is a major cause of death and disability globally. As a type of secondary injury after ICH, treatment for cell death can promote the recovery of neurological function. Methods: Among all the cell death, neuronal necroptosis has recently been demonstrated of significance in the pathogenesis of ICH. However, the administration of drugs against necroptosis has many limitations. Results: In the present study, we found that metformin, a first-line medication for the treatment of type 2 diabetes, can effectively inhibit neuronal necroptosis after ICH through activating AMPK related pathway, thereby significantly improving neurological function scores and reducing brain edema. Conclusion: These results will provide a new perspective for future research in necroptosis.

A grading scale for surgically treated patients with spontaneous supratentorial intracerebral hemorrhage: the Surgical Swedish ICH Score

2020 ◽  
Vol 133 (3) ◽  
pp. 800-807 ◽  
Author(s):  
Andreas Fahlström ◽  
Henrietta Nittby Redebrandt ◽  
Hugo Zeberg ◽  
Jiri Bartek ◽  
Andreas Bartley ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Intracerebral Hemorrhage ◽  
External Validation ◽  
Grading Scale ◽  
Ich Score ◽  
Gcs Score ◽  
Strength Of Association ◽  
Point Type ◽  
Clinical Grading

OBJECTIVEThe authors aimed to develop the first clinical grading scale for patients with surgically treated spontaneous supratentorial intracerebral hemorrhage (ICH).METHODSA nationwide multicenter study including 401 ICH patients surgically treated by craniotomy and evacuation of a spontaneous supratentorial ICH was conducted between January 1, 2011, and December 31, 2015. All neurosurgical centers in Sweden were included. All medical records and neuroimaging studies were retrospectively reviewed. Independent predictors of 30-day mortality were identified by logistic regression. A risk stratification scale (the Surgical Swedish ICH [SwICH] Score) was developed using weighting of independent predictors based on strength of association.RESULTSFactors independently associated with 30-day mortality were Glasgow Coma Scale (GCS) score (p = 0.00015), ICH volume ≥ 50 mL (p = 0.031), patient age ≥ 75 years (p = 0.0056), prior myocardial infarction (MI) (p = 0.00081), and type 2 diabetes (p = 0.0093). The Surgical SwICH Score was the sum of individual points assigned as follows: GCS score 15–13 (0 points), 12–5 (1 point), 4–3 (2 points); age ≥ 75 years (1 point); ICH volume ≥ 50 mL (1 point); type 2 diabetes (1 point); prior MI (1 point). Each increase in the Surgical SwICH Score was associated with a progressively increased 30-day mortality (p = 0.0002). No patient with a Surgical SwICH Score of 0 died, whereas the 30-day mortality rates for patients with Surgical SwICH Scores of 1, 2, 3, and 4 were 5%, 12%, 31%, and 58%, respectively.CONCLUSIONSThe Surgical SwICH Score is a predictor of 30-day mortality in patients treated surgically for spontaneous supratentorial ICH. External validation is needed to assess the predictive value as well as the generalizability of the Surgical SwICH Score.

scholarly journals Hyperinsulinemia and Its Pivotal Role in Aging, Obesity, Type 2 Diabetes, Cardiovascular Disease and Cancer

2021 ◽  
Vol 22 (15) ◽  
pp. 7797
Author(s):  
Joseph A. M. J. L. Janssen
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Insulin Secretion ◽  
Early Stage ◽  
Insulin Clearance ◽  
Future Research ◽  
Age Related ◽  
Hepatic Insulin Clearance

For many years, the dogma has been that insulin resistance precedes the development of hyperinsulinemia. However, recent data suggest a reverse order and place hyperinsulinemia mechanistically upstream of insulin resistance. Genetic background, consumption of the “modern” Western diet and over-nutrition may increase insulin secretion, decrease insulin pulses and/or reduce hepatic insulin clearance, thereby causing hyperinsulinemia. Hyperinsulinemia disturbs the balance of the insulin–GH–IGF axis and shifts the insulin : GH ratio towards insulin and away from GH. This insulin–GH shift promotes energy storage and lipid synthesis and hinders lipid breakdown, resulting in obesity due to higher fat accumulation and lower energy expenditure. Hyperinsulinemia is an important etiological factor in the development of metabolic syndrome, type 2 diabetes, cardiovascular disease, cancer and premature mortality. It has been further hypothesized that nutritionally driven insulin exposure controls the rate of mammalian aging. Interventions that normalize/reduce plasma insulin concentrations might play a key role in the prevention and treatment of age-related decline, obesity, type 2 diabetes, cardiovascular disease and cancer. Caloric restriction, increasing hepatic insulin clearance and maximizing insulin sensitivity are at present the three main strategies available for managing hyperinsulinemia. This may slow down age-related physiological decline and prevent age-related diseases. Drugs that reduce insulin (hyper) secretion, normalize pulsatile insulin secretion and/or increase hepatic insulin clearance may also have the potential to prevent or delay the progression of hyperinsulinemia-mediated diseases. Future research should focus on new strategies to minimize hyperinsulinemia at an early stage, aiming at successfully preventing and treating hyperinsulinemia-mediated diseases.

scholarly journals Current Perspectives on Management of Type 2 Diabetes in Youth

Children ◽  
2021 ◽  
Vol 8 (1) ◽  
pp. 37
Author(s):  
Sachi Singhal ◽  
Seema Kumar
Keyword(s):  
Type 2 Diabetes ◽  
Severe Obesity ◽  
Rapid Development ◽  
Adult Onset ◽  
Socioeconomically Disadvantaged ◽  
Lifestyle Modifications ◽  
First Line ◽  
Diabetes In Youth ◽  
First Line Treatment

The prevalence of type 2 diabetes mellitus (T2DM) in children and adolescents is on the rise, and the increase in prevalence of this disorder parallels the modern epidemic of childhood obesity worldwide. T2DM affects primarily post-pubertal adolescents from ethnic/racial minorities and those from socioeconomically disadvantaged backgrounds. Youth with T2DM often have additional cardiovascular risk factors at diagnosis. T2DM in youth is more progressive in comparison to adult onset T2DM and shows lower rates of response to pharmacotherapy and more rapid development of diabetes-related complications. Lifestyle modifications and metformin are recommended as the first-line treatment for youth with T2DM in the absence of significant hyperglycemia. Assessment of pancreatic autoimmunity is recommended in all youth who appear to have T2DM. Pharmacotherapeutic options for youth with T2DM are limited at this time. Liraglutide, a GLP-1 agonist, was recently approved for T2DM in adolescents 10 years of age and older. Several clinical trials are currently underway with youth with T2DM with medications that are approved for T2DM in adults. Bariatric surgery is associated with excellent rates of remission of T2DM in adolescents with severe obesity and should be considered in selected adolescents.

Strategies to enhance compliance to physical activity for patients with insulin resistance

2007 ◽  
Vol 32 (3) ◽  
pp. 549-556 ◽  
Author(s):  
Alison Kirk ◽  
Pierpaolo De Feo
Keyword(s):  
Physical Activity ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Wearable Sensors ◽  
Physical Activity Promotion ◽  
Physical Activity Behaviour ◽  
Future Research ◽  
Evidence Based ◽  
Activity Promotion

The evidence that physical activity is an effective therapeutic tool in the management of insulin resistance and type 2 diabetes is well documented. Limited research has addressed how best to promote and maintain physical activity in these individuals. This paper explores strategies to enhance compliance to physical activity for patients with insulin resistance. Several evidence-based guidelines and reviews recommend that physical activity interventions are based on a valid theoretical framework. However, there is no evidence-based consensus on the best theory or the combination of theories to use. Motivational tools such as pedometers, wearable sensors measuring energy expenditure, and point of choice prompts appear to be effective at stimulating short-term substantial increases in physical activity, but further strategies to maintain physical activity behaviour change are required. Physical activity consultation has demonstrated effective physical activity promotion over periods of up to 2 years in people with type 2 diabetes. Future research should identify the longer term effects of this intervention and the effectiveness of different methods of delivery. Overall, there needs to be a lot more focus on this area of research. Without this, the abundance of research investigating the effects of physical activity on people with insulin resistance and type 2 diabetes is essentially redundant.

scholarly journals Quinoa’s Potential to Enhance Dietary Management of Obesity and Type-2 Diabetes: A Review of the Current Evidence

Diabetology ◽  
2021 ◽  
Vol 2 (2) ◽  
pp. 77-94
Author(s):  
Alexander Little ◽  
Kevin Murphy ◽  
Patrick Solverson
Keyword(s):  
Type 2 Diabetes ◽  
Best Management Practices ◽  
Management Practices ◽  
The United States ◽  
Lipid Absorption ◽  
Current Evidence ◽  
Future Research ◽  
Dietary Management ◽  
Obesity And Diabetes

The prevalence of diet-induced obesity and type-2 diabetes remains a growing concern in the United States. As best management practices still include improved diet and physical activity, bioactive food components, contained within functional foods, show promise in curbing the cardiometabolic complications associated with excess weight and diabetes. Quinoa is an emerging candidate crop for its versatility in wide-ranging growing conditions as one approach to address food security, but it also contains several components that may serve as a dietary tool for post-industrial countries struggling with the health complications of caloric excess. Preliminary rodent feeding studies demonstrate that components within quinoa, namely, phytosteroids, phenolics, polysaccharides, and peptides, can prevent adiposity, dyslipidemia, and hyperglycemia. Mechanistic activity may involve reduced lipid absorption and adipogenesis, increased energy expenditure and glucose oxidation and corrected gut microbiota. Other intestinal actions may include blocked carbohydrate digestion with enhanced incretin signaling. Evidence in clinical trials is lacking and future research spanning cells to the clinic is needed to further elucidate the interesting preliminary reports reviewed here. Quinoa offers several unique attributes that could be harnessed to improve the dietary management of obesity and diabetes.

Does Insulin Use Worsen the Prognosis of COVID-19 Patients with Type 2 Diabetes Mellitus? A Current Update

2021 ◽  
Vol 18 ◽  
Author(s):  
Elvan Wiyarta ◽  
Wismandari Wisnu
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Disease Progression ◽  
Grey Literature ◽  
Final Analysis ◽  
Eligibility Criteria ◽  
New Perspective ◽  
Insulin Use

Background: Insulin has recently received special attention concerning its use in COVID-19 patients. Although controversial, insulin can be able to worsen the prognosis of COVID-19 patients with Type 2 Diabetes Mellitus (T2DM) through an inflammatory pathway. This uncertain aspect brings a new perspective related to insulin use in this pandemic era. Objective: We tried to collect and analyze various studies related to this issue to provide a complete picture of the prognosis of insulin use in COVID-19 patients with T2DM. Methods: We comprehensively searched PubMed, Cochrane CENTRAL, Embase, EBSCO CINAHL, MEDLINE, and grey literature databases for studies investigating the effect of insulin on COVID-19 outcomes, including mortality, hospitalization, disease progression, other prognostic surrogates. Records were screened against the eligibility criteria. Result: 2556 articles were retrieved and were screened. A total of 8 studies were included in the final analysis. There are no studies with solid evidence supporting the effect of insulin treatment on the worsening of the prognosis of COVID-19 patients with T2DM. Although several studies have shown that insulin is associated with a poor prognosis, most studies have not considered confounders. This certainly makes it challenging to analyze the effects of insulin independently. Conclusion: We propose that COVID-19 patients with T2DM continue to receive insulin, but with careful observation of the risk of disease progression.

Trends in First-Line Glucose-Lowering Drug Use in Adults With Type 2 Diabetes in Light of Emerging Evidence for SGLT-2i and GLP-1RA

Diabetes Care ◽  
2021 ◽  
pp. dc202926
Author(s):  
HoJin Shin ◽  
Sebastian Schneeweiss ◽  
Robert J. Glynn ◽  
Elisabetta Patorno
Keyword(s):  
Type 2 Diabetes ◽  
Drug Use ◽  
First Line ◽  
Glucose Lowering ◽  
Lowering Drug

977-P: Trends in First-Line Glucose-Lowering Drug Use in Adults with Type 2 Diabetes in Light of Emerging Evidence for SGLT2i and GLP-1RA

Diabetes ◽  
2021 ◽  
Vol 70 (Supplement 1) ◽  
pp. 977-P
Author(s):  
HOJIN SHIN ◽  
SEBASTIAN SCHNEEWEISS ◽  
ROBERT GLYNN ◽  
ELISABETTA PATORNO
Keyword(s):  
Type 2 Diabetes ◽  
Drug Use ◽  
First Line ◽  
Glucose Lowering ◽  
Lowering Drug

scholarly journals AC-YVAD-CMK Inhibits Pyroptosis and Improves Functional Outcome after Intracerebral Hemorrhage

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Xiao Lin ◽  
Haotuo Ye ◽  
Felix Siaw-Debrah ◽  
Sishi Pan ◽  
Zibin He ◽  
...  
Keyword(s):  
Cell Death ◽  
Intracerebral Hemorrhage ◽  
Cell Damage ◽  
Neuronal Cell ◽  
Neurological Function ◽  
Inflammatory Factors ◽  
Neuroprotective Effects ◽  
Caspase 1 ◽  
Cell Death Pathways ◽  
Cell Death Pathway

Intracerebral hemorrhage (ICH) refers to bleeding in the brain and is associated with the release of large amount of inflammasomes, and the activation of different cell death pathways. These cell death pathways lead to removal of inactivated and damaged cells and also result in neuronal cell damage. Pyroptosis is a newly discovered cell death pathway that has gained attention in recent years. This pathway mainly depends on activation of caspase-1-mediated cascades to cause cell death. We tested a well-known selective inhibitor of caspase-1, AC-YVAD-CMK, which has previously been found to have neuroprotective effects in ICH mice model, to ascertain its effects on the activation of inflammasomes mediated pyroptosis. Our results showed that AC-YVAD-CMK could reduce caspase-1 activation and inhibit IL-1β production and maturation, but has no effect on NLRP3 expression, an upstream inflammatory complex. AC-YVAD-CMK administration also resulted in reduction in M1-type microglia polarization around the hematoma, while increasing the number of M2-type cells. Furthermore, AC-YVAD-CMK treated mice showed some recovery of neurological function after hemorrhage especially at the hyperacute and subacute stage resulting in some degree of limb movement. In conclusion, we are of the view that AC-YVAD-CMK could inhibit pyroptosis, decrease the secretion or activation of inflammatory factors, and affect the polarization of microglia resulting in improvement of neurological function after ICH.

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