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PloS One 2023Aberrant brain insulin signaling has been posited to lie at the crossroads of several metabolic and cognitive disorders. Intranasal insulin (INI) is a non-invasive... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Aberrant brain insulin signaling has been posited to lie at the crossroads of several metabolic and cognitive disorders. Intranasal insulin (INI) is a non-invasive approach that allows investigation and modulation of insulin signaling in the brain while limiting peripheral side effects.
OBJECTIVES
The objective of this systematic review and meta-analysis is to evaluate the effects of INI on cognition in diverse patient populations and healthy individuals.
METHODS
MEDLINE, EMBASE, PsycINFO, and Cochrane CENTRAL were systematically searched from 2000 to July 2021. Eligible studies were randomized controlled trials that studied the effects of INI on cognition. Two independent reviewers determined study eligibility and extracted relevant descriptive and outcome data.
RESULTS
Twenty-nine studies (pooled N = 1,726) in healthy individuals as well as those with Alzheimer's disease (AD)/mild cognitive impairment (MCI), mental health disorders, metabolic disorders, among others, were included in the quantitative meta-analysis. Patients with AD/MCI treated with INI were more likely to show an improvement in global cognition (SMD = 0.22, 95% CI: 0.05-0.38 p = <0.00001, N = 12 studies). Among studies with healthy individuals and other patient populations, no significant effects of INI were found for global cognition.
CONCLUSIONS
This review demonstrates that INI may be associated with pro-cognitive benefits for global cognition, specifically for individuals with AD/MCI. Further studies are required to better understand the neurobiological mechanisms and differences in etiology to dissect the intrinsic and extrinsic factors contributing to the treatment response of INI.
Topics: Humans; Insulin; Cognitive Dysfunction; Alzheimer Disease; Cognition; Cognition Disorders
PubMed: 37379265
DOI: 10.1371/journal.pone.0286887 -
The Journal of Clinical Endocrinology... Dec 2023Polycystic ovary syndrome (PCOS) is a complex genetic trait and the most common endocrine disorder of women, clinically evident in 5% to 15% of reproductive-aged women...
PURPOSE
Polycystic ovary syndrome (PCOS) is a complex genetic trait and the most common endocrine disorder of women, clinically evident in 5% to 15% of reproductive-aged women globally, with associated cardiometabolic dysfunction. Adipose tissue (AT) dysfunction appears to play an important role in the pathophysiology of PCOS even in patients who do not have excess adiposity.
METHODS
We undertook a systematic review concerning AT dysfunction in PCOS, and prioritized studies that assessed AT function directly. We also explored therapies that targeted AT dysfunction for the treatment of PCOS.
RESULTS
Various mechanisms of AT dysfunction in PCOS were identified including dysregulation in storage capacity, hypoxia, and hyperplasia; impaired adipogenesis; impaired insulin signaling and glucose transport; dysregulated lipolysis and nonesterified free fatty acids (NEFAs) kinetics; adipokine and cytokine dysregulation and subacute inflammation; epigenetic dysregulation; and mitochondrial dysfunction and endoplasmic reticulum and oxidative stress. Decreased glucose transporter-4 expression and content in adipocytes, leading to decreased insulin-mediated glucose transport in AT, was a consistent abnormality despite no alterations in insulin binding or in IRS/PI3K/Akt signaling. Adiponectin secretion in response to cytokines/chemokines is affected in PCOS compared to controls. Interestingly, epigenetic modulation via DNA methylation and microRNA regulation appears to be important mechanisms underlying AT dysfunction in PCOS.
CONCLUSION
AT dysfunction, more than AT distribution and excess adiposity, contributes to the metabolic and inflammation abnormalities of PCOS. Nonetheless, many studies provided contradictory, unclear, or limited data, highlighting the urgent need for additional research in this important field.
Topics: Humans; Female; Adult; Polycystic Ovary Syndrome; Insulin Resistance; Phosphatidylinositol 3-Kinases; Adipose Tissue; Insulin; Cytokines; Obesity; Inflammation; Glucose
PubMed: 37329216
DOI: 10.1210/clinem/dgad356 -
International Journal of Molecular... May 2023Obesity is a growing public health problem worldwide, and GH and IGF-1 have been studied as potential therapeutic targets for managing this condition. This review... (Review)
Review
Obesity is a growing public health problem worldwide, and GH and IGF-1 have been studied as potential therapeutic targets for managing this condition. This review article aims to provide a comprehensive view of the interplay between GH and IGF-1 and metabolism within the context of obesity. We conducted a systematic review of the literature that was published from 1993 to 2023, using MEDLINE, Embase, and Cochrane databases. We included studies that investigated the effects of GH and IGF-1 on adipose tissue metabolism, energy balance, and weight regulation in humans and animals. Our review highlights the physiological functions of GH and IGF-1 in adipose tissue metabolism, including lipolysis and adipogenesis. We also discuss the potential mechanisms underlying the effects of these hormones on energy balance, such as their influence on insulin sensitivity and appetite regulation. Additionally, we summarize the current evidence regarding the efficacy and safety of GH and IGF-1 as therapeutic targets for managing obesity, including in pharmacological interventions and hormone replacement therapy. Finally, we address the challenges and limitations of targeting GH and IGF-1 in obesity management.
Topics: Animals; Humans; Insulin-Like Growth Factor I; Growth Hormone; Obesity; Adipose Tissue; Insulin; Human Growth Hormone
PubMed: 37298507
DOI: 10.3390/ijms24119556 -
Nutrition Reviews Jan 2024There is substantial evidence that reduced short-chain fatty acids (SCFAs) in the gut are associated with obesity and type 2 diabetes, although findings from clinical... (Meta-Analysis)
Meta-Analysis
CONTEXT
There is substantial evidence that reduced short-chain fatty acids (SCFAs) in the gut are associated with obesity and type 2 diabetes, although findings from clinical interventions that can increase SCFAs are inconsistent.
OBJECTIVE
This systematic review and meta-analysis aimed to assess the effect of SCFA interventions on fasting glucose, fasting insulin, and homeostatic model assessment of insulin resistance (HOMA-IR).
DATA SOURCES
Relevant articles published up to July 28, 2022, were extracted from PubMed and Embase using the MeSH (Medical Subject Headings) terms of the defined keywords [(short-chain fatty acids) AND (obesity OR diabetes OR insulin sensitivity)] and their synonyms. Data analyses were performed independently by two researchers who used the Cochrane meta-analysis checklist and the PRISMA guidelines.
DATA EXTRACTION
Clinical studies and trials that measured SCFAs and reported glucose homeostasis parameters were included in the analysis. Standardized mean differences (SMDs) with 95%CIs were calculated using a random-effects model in the data extraction tool Review Manager version 5.4 (RevMan 5.4). The risk-of-bias assessment was performed following the Cochrane checklist for randomized and crossover studies.
DATA ANALYSIS
In total, 6040 nonduplicate studies were identified, 23 of which met the defined criteria, reported fasting insulin, fasting glucose, or HOMA-IR values, and reported change in SCFA concentrations post intervention. Meta-analyses of these studies indicated that fasting insulin concentrations were significantly reduced (overall effect: SMD = -0.15; 95%CI = -0.29 to -0.01, P = 0.04) in treatment groups, relative to placebo groups, at the end of the intervention. Studies with a confirmed increase in SCFAs at the end of intervention also had a significant effect on lowering fasting insulin (P = 0.008). Elevated levels of SCFAs, compared with baseline levels, were associated with beneficial effects on HOMA-IR (P < 0.00001). There was no significant change in fasting glucose concentrations.
CONCLUSION
Increased postintervention levels of SCFAs are associated with lower fasting insulin concentrations, offering a beneficial effect on insulin sensitivity.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO registration number CRD42021257248.
Topics: Humans; Insulin Resistance; Diabetes Mellitus, Type 2; Insulin; Obesity; Glucose; Fatty Acids, Volatile; Blood Glucose
PubMed: 37290429
DOI: 10.1093/nutrit/nuad042 -
Frontiers in Endocrinology 2023Despite the fact that some evidence suggests that the administration of 17β-estradiol plus norethisterone acetate influences glucose and insulin metabolism in women,... (Meta-Analysis)
Meta-Analysis
The influence of 17β-estradiol plus norethisterone acetate treatment on markers of glucose and insulin metabolism in women: a systematic review and meta-analysis of randomized controlled trials.
OBJECTIVE
Despite the fact that some evidence suggests that the administration of 17β-estradiol plus norethisterone acetate influences glucose and insulin metabolism in women, these findings are still contradictory. Thus, we aimed to examine the impact of the co-administration of 17β-estradiol and norethisterone acetate on glycated haemoglobin (HbA1c), fasting glucose, insulin and C-peptide concentrations in females by means of a systematic review and meta-analysis of randomized controlled trials (RCTs).
METHODS
We searched four databases (PubMed/MEDLINE, Scopus, Embase, and Web of Science) using specific keywords and word combinations. The random-effects model (DerSimonian and Laird model) was employed to compute the weighted mean difference (WMD) and 95% confidence intervals (CIs) for the variations from baseline of HbA1c, fasting glucose, insulin, and C-peptide concentrations.
RESULTS
In total, 14 RCTs were entered into the quantitative synthesis. The combined administration of 17β-estradiol and norethisterone acetate decreased HbA1c (WMD: -0.65%, 95% CI: -1.15 to -0.15; P=0.011), fasting glucose (WMD: -11.05 mg/dL, 95% CI: -16.6 to -5.5; P<0.001) and insulin (WMD: -1.35 mIU/L, 95% CI: -2.20 to -0.50; P=0.001) levels. C-peptide concentrations' declined only in females diagnosed with overweight/obesity or diabetes.
CONCLUSION
Evidence to date points out that the administration of 17β-estradiol and norethisterone acetate has a positive impact on glucose metabolism in women by reducing fasting glucose, HbA1c, and insulin values. Future studies need to confirm the potential benefits of this drug combination in the prevention and/or management of cardiometabolic disorders.
Topics: Female; Humans; Glucose; Norethindrone Acetate; Blood Glucose; Glycated Hemoglobin; C-Peptide; Randomized Controlled Trials as Topic; Insulin; Estradiol
PubMed: 37265701
DOI: 10.3389/fendo.2023.1137406 -
Archives of Endocrinology and Metabolism May 2023Insulin Icodec is a novel basal insulin analogue designed for once-weekly administration, therefore might propitiate reduction in the frequency of injections and... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Insulin Icodec is a novel basal insulin analogue designed for once-weekly administration, therefore might propitiate reduction in the frequency of injections and facilitate treatment adherence. This study aimed to determine the glycemic control and safety profile of Insulin Icodec, compared with Glargine U100 in patients with diabetes mellitus type 2.
MATERIALS AND METHODS
We performed a systematic review and meta-analysis of randomized controlled trials (RCT) data comparing OnceWeekly Insulin Icodec and Once-Daily Insulin Glargine U100 in patients with type 2 diabetes mellitus. PubMed, Embase, and Cochrane databases were searched for trials published up to May 14, 2022. Data were extracted from published reports and quality assessment was performed per Cochrane recommendations.
RESULTS
Three studies were included comprising 453 patients, 230 (50.77%) using Once-Weekly Insulin Icodec and 223 (49.22%) using Once-Daily Insulin Glargine U100. In the pooled data, Glycated Hemoglobin (MD -0.20% CI -0.33 to -0.07%; P=0.002) change from baseline demonstrated a significantly higher reduction in the Icodec group. Time with Glucose in Range (MD 6.60% CI 3.63 to 9.57%; P < 0.0001) and Insulin Dose Difference (MD 0.97UI CI 0.76 to 1.18UI; P < 0.0001) were higher in the Icodec group. There was no significant difference in fasting plasma glucose, body weight change, hypoglycemia or any adverse event evaluated.
CONCLUSION
OnceWeekly Insulin Icodec was associated with a small reduction in Glycated Hemoglobin, as well as higher Time with Glucose in Range, with similar hypoglycemic adverse events, when compared with Once-Daily Insulin Glargine U100.
Topics: Humans; Insulin Glargine; Glycated Hemoglobin; Blood Glucose; Randomized Controlled Trials as Topic; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Insulin; Glucose; Clinical Trials, Phase II as Topic
PubMed: 37249450
DOI: 10.20945/2359-3997000000614 -
Drug Discoveries & Therapeutics Jul 2023Traditional medicines are recently being focused on to treat diabetes and its complications because of their lack of toxic and/or side effects. This report describes the...
Traditional medicines are recently being focused on to treat diabetes and its complications because of their lack of toxic and/or side effects. This report describes the effects of 7-O-galloyl-D-sedoheptulose (GS), a polyphenolic compound isolated from Corni Fructus, on type 2 diabetic db/db mice with hepatic and pancreatic damage. We examined several biochemical factors and oxidative stress- and inflammation-related markers. In the serum, levels of glucose, leptin, insulin, C-peptide, resistin, tumor necrosis factor-α, and interleukin-6 were down-regulated, while adiponectin was augmented by GS treatment. In addition, GS suppressed the reactive oxygen species and lipid peroxidation in the serum, liver, and pancreas, but increased the pancreatic insulin and pancreatic C-peptide contents. These results were derived from attenuating the expression of nicotinamide adenine dinucleotide phosphate oxidase subunit proteins, Nox-4 and p22. Augmented nuclear factor (NF)-E2-related factor 2 and heme oxygenase-1 were reduced with a decrease in oxidative stress during GS treatment. NF-κB-related pro-inflammatory factors were also alleviated in hepatic tissue. Moreover, GS modulated the protein expressions of pro-inflammatory NF-κB, cyclooxygenase-2, inducible nitric oxide synthase, c-Jun N-terminal kinase (JNK), phosphor-JNK, activator protein-1, transforming growth factor-β, and fibronectin. Based on these results, we demonstrated that the anti-diabetic action of GS may be due to its anti-oxidative stress property and anti-inflammatory action.
Topics: Mice; Animals; Cornus; Diabetes Mellitus, Type 2; Polyphenols; NF-kappa B; Diabetes Mellitus, Experimental; C-Peptide; Liver; Pancreas; Insulin
PubMed: 37245985
DOI: 10.5582/ddt.2022.01097 -
Nutrients May 2023Dietary fiber (DF) consumption has been associated with improved glycemic control in epidemiological and long-term interventional studies. However, its acute effects are... (Review)
Review
Dietary fiber (DF) consumption has been associated with improved glycemic control in epidemiological and long-term interventional studies. However, its acute effects are not yet clear. This systematic review aims to elucidate the postprandial effects of DF in starchy products on glycemia and insulinemia. An electronic search of databases was conducted, and forty-one records met the inclusion criteria and underwent a risk-of-bias assessment. It was shown that soluble DF does not clearly affect glycemia in individuals with normal weight, while resistant starch may be more effective in flattening glycemic responses. Concerning insulinemia, both soluble DF and resistant starch have mixed results, with either favorable or no effects. Data on insoluble DF and glucose metabolism are scarce. The same mixed results for glycemia can be seen in healthy volunteers with overweight/obesity, while resistant starch seems to improve insulinemic responses. Finally, more studies need to examine the acute effects of DF in starchy foods on glucose metabolism and insulin secretion in individuals facing glucose abnormalities. Additionally, more studies are needed to prove whether ingesting high-fiber carbohydrate-containing products per se can result in blunted glycemic and insulinemic responses and which DF type and amount are more effective.
Topics: Humans; Blood Glucose; Dietary Carbohydrates; Insulin; Resistant Starch; Cross-Over Studies; Glucose; Dietary Fiber; Postprandial Period; Glycemic Index
PubMed: 37242267
DOI: 10.3390/nu15102383 -
BMC Musculoskeletal Disorders May 2023Hip fracture is a major health problem that occurs more often in the elderly, especially in diabetic patients. Some studies have been conducted regarding the effect of... (Meta-Analysis)
Meta-Analysis
The use of metformin, sulfonylurea compounds and insulin and the risk of hip fractures in diabetic patients: a systematic review and meta-analysis of observational studies.
BACKGROUND
Hip fracture is a major health problem that occurs more often in the elderly, especially in diabetic patients. Some studies have been conducted regarding the effect of anti- diabetic drugs on fractures. But so far, no meta-analysis study has been conducted to investigate the effect of diabetic drugs on hip fractures. Therefore, this study investigated the relationship between anti-diabetic drugs (Metformin, Sulfonylurea, and insulin) with hip fractures.
METHODS
In this systematic review and meta analysis study, PubMed, Scopus, Google Scholar, and Web of Science databases were searched with specific keywords to find relevant studies. Two researchers included related studies after screening based on the title and full text. Cochran's Q and I2 tests were used to assess heterogeneity between studies. Publication bias between studies was evaluated for each drug using Egger's test. A 95% confidence interval was used for effect size significance. Overall, 49 studies, including 6,631,297 participants, were reviewed.
RESULTS
The results showed that metformin significantly reduced the risk of hip fracture (HR: 0.833, 95% CI: 0.759, 0.914, P:0.001). Consumption of sulfonylurea compounds was significantly associated with an increased risk of hip fracture. (HR: 1.175, 95% CI:1.068,1.293, P:0.001), The risk of hip fracture in patients receiving insulin was significantly higher than in diabetic patients who did not receive insulin. (HR:1.366, 95% CI:1.226,1.522, P:0.001).
CONCLUSION
The results of this study showed that taking metformin reduces the risk of hip fracture, and insulin and Sulfonylurea increase the risk of hip fracture.
Topics: Aged; Humans; Insulin; Hip Fractures; Sulfonylurea Compounds; Databases, Factual; Metformin; Diabetes Mellitus
PubMed: 37161384
DOI: 10.1186/s12891-023-06493-9 -
PloS One 2023Tirzeptide is a novel glucagon-like peptide-1 receptor (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) drug, which shows good efficiency for weight loss.... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Tirzeptide is a novel glucagon-like peptide-1 receptor (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) drug, which shows good efficiency for weight loss. Therefore, we aim to investigate the efficacy and safety of tirzepatide for weight loss in type 2 diabetes mellitus (T2DM) and obesity patients in this meta-analysis study.
METHODS
Cochrane Library, PubMed, Embase, Clinical Trials, and Web of Science were searched from inception to October 5, 2022. All randomized controlled trials (RCTs) were included. The odds ratio (OR) was calculated using fixed-effects or random-effects models by Review Manager 5.3 software.
RESULTS
In total, ten studies (12 reports) involving 9,873 patients were identified. A significant loss body weight in the tirzepatide group versus the placebo by -9.81 kg (95% CI (-12.09, -7.52), GLP-1 RAs by -1.05 kg (95% CI (-1.48, -0.63), and insulin by -1.93 kg (95% CI (-2.81, -1.05), respectively. In sub-analysis, the body weight of patients was significantly reduced in three tirzepatide doses (5 mg, 10 mg, and 15 mg) when compared with those of the placebo/GLP-1 RA/insulin. In terms of safety, the incidence of any adverse events and adverse events leading to study drug discontinuation was higher in the tirzepatide group, but the incidence of serious adverse events and hypoglycaemia was lower. Additionally, the gastrointestinal adverse events (including diarrhea, nausea, vomiting and decreased appetite) of tirzepatide were higher than those of placebo/basal insulin, but similar to GLP-1 RAs.
CONCLUSION
In conclusion, tirzeptide can significantly reduce the weight of T2DM and patient with obesity, and it is a potential therapeutic regimen for weight-loss, but we need to be vigilant about its gastrointestinal reaction.
Topics: Humans; Hypoglycemic Agents; Diabetes Mellitus, Type 2; Gastric Inhibitory Polypeptide; Insulin; Weight Loss; Obesity; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor
PubMed: 37141329
DOI: 10.1371/journal.pone.0285197