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European Journal of Clinical... Nov 2023The association between non-alcoholic fatty liver disease (NAFLD) and metabolic disorders, especially type-2 diabetes (T2DM), has been proven to be bidirectional.... (Review)
Review
Comparison of the efficacy and safety of hypoglycemic treatments in patients with non-alcoholic fatty liver disease and type-2 diabetes: a systematic review and Bayesian network analysis.
PURPOSE
The association between non-alcoholic fatty liver disease (NAFLD) and metabolic disorders, especially type-2 diabetes (T2DM), has been proven to be bidirectional. Hypoglycemic agents may be promising treatments for those disorders. However, there is currently no approved hypoglycemic therapy for NAFLD. In this review, we aimed to compare the efficacy and safety of twelve different hypoglycemic treatments in patients with NAFLD and T2DM.
METHODS
We systematically screened randomized controlled trials (RCTs) published from March 2013 to March 2023 by searching PubMed, Embase, Medline, and Web of Science without any language restriction. We registered this project on the PROSPERO website: https://www.crd.york.ac.uk/PROSPERO/ (ID: CRD42023429701). All subsequent analyses were performed under the registered protocol. The mean difference (MD) and 95% confidence interval (95% CI) were adapted to evaluate the effect size of the treatment. The surface under the cumulative sorting curve (SUCRA) was used to rank the efficacy of the included treatments.
RESULTS
We included 19 trials involving 1212 patients in total. Insulin plus glucagon-like peptide-1 receptor agonist (GLP1RA) combination therapy was probably the most effective treatment for reducing weight and body mass index (BMI) (SUCRA: 0.93 and 1.00). Thiazolidinediones (TZD) were probably the most effective treatment for reducing glycosylated hemoglobin (HbA1c) and γ-glutamyltranspeptidase (γ-GGT) levels (SUCRA: 0.78 and 0.97). Sodium-glucose cotransporter 2 inhibitors (SGLT2i) had the highest probability of presenting good therapeutic efficacy in reducing triglyceride (TG) levels (SUCRA: 0.72). The most common adverse reactions were gastrointestinal disorders, mainly after the administration of GLP1RA, and mild hypoglycemia, which was closely related to the use of insulin.
CONCLUSION
GLP1RA plus insulin combination therapy, GLP1RA, SGLT2i, and TZD may be the most effective therapeutic methods for patients with NAFLD and T2DM.
Topics: Humans; Hypoglycemic Agents; Non-alcoholic Fatty Liver Disease; Diabetes Mellitus, Type 2; Insulin; Thiazolidinediones
PubMed: 37682287
DOI: 10.1007/s00228-023-03561-w -
European Journal of Epidemiology Apr 2022Physical inactivity in individuals with spinal cord injury (SCI) has been suggested to be an important determinant of increased cardiometabolic disease (CMD) risk.... (Meta-Analysis)
Meta-Analysis Review
Physical inactivity in individuals with spinal cord injury (SCI) has been suggested to be an important determinant of increased cardiometabolic disease (CMD) risk. However, it remains unclear whether physically active SCI individuals as compared to inactive or less active individuals have truly better cardiometabolic risk profile. We aimed to systematically review and quantify the association between engagement in regular physical activity and/or exercise interventions and CMD risk factors in individuals with SCI. Four medical databases were searched and studies were included if they were clinical trials or observational studies conducted in adult individuals with SCI and provided information of interest. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was applied to rate the certainty of evidence. Of 5816 unique citations, 11 randomized clinical trials, 3 non-randomized trial and 32 cross-sectional studies comprising more than 5500 SCI individuals were included in the systematic review. In meta-analysis of RCTs and based on evidence of moderate certainty, physical activity in comparison to control intervention was associated with: (i) better glucose homeostasis profile [WMD of glucose, insulin and Assessment of Insulin Resistance (HOMA-IR) were - 3.26 mg/dl (95% CI - 5.12 to - 1.39), - 3.19 μU/ml (95% CI - 3.96 to - 2.43)] and - 0.47 (95% CI - 0.60 to - 0.35), respectively], and (ii) improved cardiorespiratory fitness [WMD of relative and absolute oxygen uptake relative (VO) were 4.53 ml/kg/min (95% CI 3.11, 5.96) and 0.26 L/min (95% CI 0.21, 0.32) respectively]. No differences were observed in blood pressure, heart rate and lipids (based on evidence of low/moderate certainty). In meta-analysis of cross-sectional studies and based on the evidence of very low to low certainty, glucose [WMD - 3.25 mg/dl (95% CI - 5.36, - 1.14)], insulin [- 2.12 μU/ml (95% CI - 4.21 to - 0.03)] and total cholesterol [WMD - 6.72 mg/dl (95% CI - 13.09, - 0.34)] were lower and HDL [WMD 3.86 mg/dl (95% CI 0.66, 7.05)] and catalase [0.07 UgHb-1 (95% CI 0.03, 0.11)] were higher in physically active SCI individuals in comparison to reference groups. Based on limited number of cross-sectional studies, better parameters of systolic and diastolic cardiac function and lower carotid intima media thickness were found in physically active groups. Methodologically sound clinical trials and prospective observational studies are required to further elaborate the impact of different physical activity prescriptions alone or in combination with other life-style interventions on CMD risk factors in SCI individuals.
Topics: Adult; Humans; Cardiometabolic Risk Factors; Carotid Intima-Media Thickness; Cross-Sectional Studies; Exercise; Glucose; Insulins; Observational Studies as Topic; Spinal Cord Injuries; Clinical Trials as Topic
PubMed: 35391647
DOI: 10.1007/s10654-022-00859-4 -
Diabetes Research and Clinical Practice Apr 2022We performed a systematic review and meta-analysis to investigate the effects of high-intensity interval training (HIIT) on postprandial glucose (PPG) and insulin (PPI)... (Meta-Analysis)
Meta-Analysis Review
AIMS
We performed a systematic review and meta-analysis to investigate the effects of high-intensity interval training (HIIT) on postprandial glucose (PPG) and insulin (PPI) versus non-exercise control and moderate-intensity continuous training (MICT) in participants with both normal and impaired glucose.
METHODS
The PubMed, Scopus, and Web of Science electronic databases were searched up to October 2021 for randomized trials evaluating HIIT versus control and/or versus MICT on glucose and insulin AUC using oral glucose tolerance testing. Subgroup analyses based on intervention duration (short-duration < 8 weeks, moderate-duration ≥ 8 weeks), baseline glucose levels (normal glucose and impaired glucose) and type of HIIT (L-HIIT and SIT) were also conducted across included studies.
RESULTS
A total of 25 studies involving 870 participants were included in the current meta-analysis. HIIT effectively reduced glucose [-0.37 (95% CI -0.60 to -0.13), p = 0.002] and insulin [-0.36 (95% CI -0.68 to -0.04), p = 0.02] AUC when compared with a CON group. Reductions in glucose AUC were significant for those with impaired glucose at baseline (p = 0.03), but not for those with normal glucose levels (p = 0.11) and following moderate-duration (p = 0.01), but not short-duration interventions (p = 0.18). However, there were no differences in glucose (p = 0.76) or insulin (p = 0.43) AUC between HIIT and MICT intervention arms.
CONCLUSIONS
Our results demonstrated that both HIIT and MICT are effective for reducing postprandial glycemia and insulinemia, particularly by moderate-duration interventions, and in those with impaired glucose.
Topics: Blood Glucose; Glucose; High-Intensity Interval Training; Humans; Insulin; Insulin, Regular, Human
PubMed: 35271876
DOI: 10.1016/j.diabres.2022.109815 -
Frontiers in Endocrinology 2023Insulin-like growth factor binding protein-1 (IGFBP-1) is considered a decline in polycystic ovary syndrome (PCOS), but it remains controversial that whether such... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Insulin-like growth factor binding protein-1 (IGFBP-1) is considered a decline in polycystic ovary syndrome (PCOS), but it remains controversial that whether such reduction is attributed to obesity.
AIMS
This systematic review aims to explore whether IGFBP-1 is reduced in PCOS, and whether such reduction is associated with obesity.
RESULTS
Our pooled study included 12 studies with a total of 450 participants. IGFBP-1 levels in PCOS were significantly lower than that in non-PCOS (SMD (95%CI)=-0.49(-0.89, -0.09), =0.02). No significant difference in IGFBP-1 levels between patients with or without PCOS classified by BMI. Whilst, stratification by PCOS status revealed a significant decrease in IGFBP-1 in overweight (SMD (95%CI)=-0.92(-1.46, -0.37), P=0.001). When comparing fasting insulin in the same way, PCOS patients had significantly elevated fasting insulin level but not statistically declined IGFBP-1 after classified by BMI.
CONCLUSION
This meta-analysis provides evidence that the decrease of IGFBP-1 in PCOS was more strongly influenced by comorbid obesity than by PCOS itself. Additionally, contrast to previous findings that insulin significantly suppresses IGFBP-1, our results suggested that the suppression of PCOS-related hyperinsulinemia on IGFBP-1 seemed diminished. Overall, our work may provide a novel perspective on the mechanism between insulin and IGFBP-1 underlying PCOS development.
Topics: Female; Humans; Insulin; Insulin-Like Growth Factor Binding Protein 1; Insulin-Like Peptides; Obesity; Polycystic Ovary Syndrome
PubMed: 38174331
DOI: 10.3389/fendo.2023.1279717 -
Pituitary Feb 2023In the past few decades, acromegaly and colonic polyps have been associated with an increased risk of colorectal cancer. Previous studies highlighted the importance of... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
In the past few decades, acromegaly and colonic polyps have been associated with an increased risk of colorectal cancer. Previous studies highlighted the importance of serum biomarkers of colonic polyps in patients with acromegaly.
METHODS
We reviewed studies on serum biomarkers of colonic polyps in patients with acromegaly, published on PubMed, Embase, Cochrane Library, Medline, and Chinese databases from January 1, 1966, to May 8, 2022. Meta-analysis and systematic review were conducted using Stata MP 14.0.
RESULTS
Eight articles were included in this study. The mean (standard deviation) concentrations of serum biomarkers for acromegaly with and without colorectal polyps were extracted from these studies. Meta-analysis results showed that, compared to patients without colonic polyps, the levels of insulin-like growth factor-1 × upper limit of normal range (IGF-1 × ULN) and fasting insulin were significantly increased; while the levels of growth hormone (GH) were significantly decreased in patients with acromegaly and colonic polyps (IGF-1 × ULN: SMD 0.23; 95% CI 0.03-0.42, p < 0.05) (fasting insulin: SMD 0.95; 9 5% CI 0.11-1.8, p < 0.05) (GH: SMD - 0.25; 95% CI - 0.41 to - 0.08, p < 0.05). IGF-1 and FPG levels did not differ significantly (IGF-1: SMD -0.03; 95% CI - 0.22 to 0.17, p > 0.05) (FPG: SMD 0.14; 95% CI - 0.23 to 0.52, p > 0.05). The systematic review results suggest no significant differences in hemoglobin A1C, TSH, free thyroxine, FT4, T3, PRL, total cholesterol, HDL, LDL, fibrinogen, clathrate antigen, serum antigen 19-9, and α-fetoprotein levels, but serum Klotho levels.
CONCLUSION
We present the first meta-analysis and systematic review of serum biomarkers in patients with acromegaly or colonic polyps. The prevalence of colonic lesion polyps, is associated with higher IGF-1 × ULN levels, higher insulin levels in acromegaly. Further research is required to confirm GH and serum soluble Klotho levels as biomarkers of colonic polyps. When IGF-1 × ULN, fasting insulin levels change in patients with acromegaly, the occurrence of colonic polyps should be monitored. Early detection may reduce the possibility of developing malignant colon neoplasms.
Topics: Humans; Acromegaly; Colonic Polyps; Insulin-Like Growth Factor I; Growth Hormone; Human Growth Hormone; Insulin; Biomarkers
PubMed: 36542278
DOI: 10.1007/s11102-022-01287-z -
Journal of General Internal Medicine Aug 2021Increasing availability of competing biosimilar alternatives makes it challenging to make treatment decisions. The purpose of this review is to evaluate the comparative... (Meta-Analysis)
Meta-Analysis Review
Comparative Efficacy and Safety of Ultra-Long-Acting, Long-Acting, Intermediate-Acting, and Biosimilar Insulins for Type 1 Diabetes Mellitus: a Systematic Review and Network Meta-Analysis.
BACKGROUND
Increasing availability of competing biosimilar alternatives makes it challenging to make treatment decisions. The purpose of this review is to evaluate the comparative efficacy and safety of ultra-long-/long-/intermediate-acting insulin products and biosimilar insulin compared to human/animal insulin in adults with type 1 diabetes mellitus (T1DM).
METHODS
MEDLINE, EMBASE, CENTRAL, and grey literature were searched from inception to March 27, 2019. Randomized controlled trials (RCTs), quasi-experimental studies, and cohort studies of adults with T1DM receiving ultra-long-/long-/intermediate-acting insulin, compared to each other, as well as biosimilar insulin compared to human/animal insulin were eligible for inclusion. Two reviewers independently screened studies, abstracted data, and appraised risk-of-bias. Pairwise meta-analyses and network meta-analyses (NMA) were conducted. Summary effect measures were mean differences (MD) and odds ratios (OR).
RESULTS
We included 65 unique studies examining 14,200 patients with T1DM. Both ultra-long-acting and long-acting insulin were superior to intermediate-acting insulin in reducing A1c, FPG, weight gain, and the incidence of major, serious, or nocturnal hypoglycemia. For fasting blood glucose, long-acting once a day (od) was superior to long-acting twice a day (bid) (MD - 0.44, 95% CI: - 0.81 to - 0.06) and ultra-long-acting od was superior to long-acting bid (MD - 0.73, 95% CI - 1.36 to - 0.11). For weight change, long-acting od was inferior to long-acting bid (MD 0.58, 95% CI: 0.05 to 1.10) and long-acting bid was superior to long-action biosimilar od (MD - 0.90, 95% CI: - 1.67 to - 0.12).
CONCLUSIONS
Our results can be used to tailor insulin treatment according to the desired results of patients and clinicians and inform strategies to establish a competitive clinical market, address systemic barriers, expand the pool of potential suppliers, and favor insulin price reduction.
PROSPERO REGISTRATION
CRD42017077051.
Topics: Biosimilar Pharmaceuticals; Diabetes Mellitus, Type 1; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin, Long-Acting; Network Meta-Analysis
PubMed: 33742305
DOI: 10.1007/s11606-021-06642-7 -
Journal of Diabetes and Its... Oct 2023One of the greatest barriers to the treatment of T2DM is nonadherence which particularly applies to insulin therapy. There is a need for a comprehensive overview of all... (Review)
Review
BACKGROUND AND AIM
One of the greatest barriers to the treatment of T2DM is nonadherence which particularly applies to insulin therapy. There is a need for a comprehensive overview of all factors associated with nonadherence to insulin therapy. The aim of this study was to identify factors associated with adherence or nonadherence to insulin therapy among adults with T2DM.
METHODS
A scoping review was conducted in accordance with the PRISMA 2020 statement. A systematic search was performed in PubMed, Cinahl, and Web of Science (January 2013 to March 2023).
RESULTS
A final sample of 48 studies was included in the scoping review. The synthesis revealed 30 factors associated with adherence or nonadherence. The factors were grouped into 6 themes: demographics, attitude and perceptions, management of diabetes, impact on daily living, disease and medication, and healthcare system.
CONCLUSION
The most prominent factors identified were age, cost of healthcare, personal beliefs towards insulin therapy, social stigma, patient education, complexity of diabetes treatment, impact of insulin therapy on daily life, and fear of side effects. The results indicate a need for further research to determine threshold values for the factors associated with adherence or nonadherence.
Topics: Humans; Adult; Diabetes Mellitus, Type 2; Insulin; Medication Adherence; Insulin, Regular, Human; Drug-Related Side Effects and Adverse Reactions
PubMed: 37651772
DOI: 10.1016/j.jdiacomp.2023.108596 -
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 -
Nutrition Reviews Aug 2023In preclinical Alzheimer's disease (AD), the brain gradually becomes insulin resistant. As a result, brain glucose utilization is compromised, causing a cellular energy... (Meta-Analysis)
Meta-Analysis
CONTEXT
In preclinical Alzheimer's disease (AD), the brain gradually becomes insulin resistant. As a result, brain glucose utilization is compromised, causing a cellular energy deficit that leads to the accumulation of free radicals, which increases inflammation and damages neurons. When glucose utilization is impaired, ketone bodies offer an alternative energy source. Ketone bodies are synthesized from fats, obtained from either the diet or adipose tissue. Dietary medium-chain fatty acids (MCFAs), which are preferentially metabolized into ketone bodies, have the potential to supply the insulin-resistant brain with energy.
OBJECTIVE
This systematic review and meta-analysis aims to review the effect of MCFA supplements on circulating ketone bodies and cognition in individuals with subjective cognitive decline, mild cognitive impairment, and AD.
DATA SOURCES
A comprehensive search of electronic databases was performed on August 12, 2019, to retrieve all publications meeting the inclusion criteria. Alerts were then set to identify any publications after the search date up until January 31, 2021.
DATA EXTRACTION
Data were extracted by 2 authors and assessed by a third. In total, 410 publications were identified, of which 16 (n = 17 studies) met the inclusion criteria.
DATA ANALYSIS
All studies assessing change in levels of blood ketone bodies due to MCFA supplementation (n = 12) reported a significant increase. Cognition outcomes (measured in 13 studies), however, varied, ranging from no improvement (n = 4 studies) to improvement (n = 8 studies) or improvement only in apolipoprotein E allele 4 (APOE ε4) noncarriers (n = 2 studies). One study reported an increase in regional cerebral blood flow in APOE ε4 noncarriers and another reported an increase in energy metabolism in the brain.
CONCLUSION
MCFA supplementation increases circulating ketone body levels, resulting in increased brain energy metabolism. Further research is required to determine whether this MCFA-mediated increase in brain energy metabolism improves cognition.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO registration number CRD42019146967.
Topics: Humans; Alzheimer Disease; Apolipoprotein E4; Fatty Acids; Ketone Bodies; Insulin; Glucose
PubMed: 36633304
DOI: 10.1093/nutrit/nuac104 -
Diabetes, Obesity & Metabolism Dec 2023To summarize the evidence of recently published randomized controlled trials (RCTs) studying efficacy, in terms of glycaemic control, and safety of the newly developed... (Meta-Analysis)
Meta-Analysis
AIM
To summarize the evidence of recently published randomized controlled trials (RCTs) studying efficacy, in terms of glycaemic control, and safety of the newly developed once-weekly basal insulin analogues.
METHODS
A systematic literature search was conducted through Medline (via PubMed), Cochrane Library and Google Scholar until June 30, 2023. Double-independent study selection, data extraction and quality assessment were performed. Results were summarized with random-effects meta-analysis.
RESULTS
A total of 3962 patients with type 2 diabetes mellitus (T2DM) among nine RCTs were analysed. All RCTs had low risk of bias according to the Cochrane Collaboration risk-of-bias tool (RoB2). Once-weekly insulins demonstrated better efficacy in glycated haemoglobin (HbA1c) reduction (mean difference [MD] -0.13%, 95% confidence interval [CI] -0.23, -0.03; P = 0.08) and a significantly greater time in range compared with once-daily insulin analogues (MD 3.54%, 95% CI 1.56, 5.53; P = 0.005). Based on subgroup analyses, the reduction in HbA1c and the odds of achieving an end-of-treatment HbA1c <6.5% were significantly greater for icodec compared to the once-daily insulin (MD -0.18%, 95% CI -0.27, -0.09 [P < 0.001] and odds ratio [OR] 1.75, 95% CI 1.34, 2.29 [P < 0.001], respectively). Once-weekly insulins were associated with higher odds of level 1 hypoglycaemia during the 24-hour period (OR 1.3, 95% CI 1.04, 1.64; P = 0.02) but were safer in terms of level 2 or 3 nocturnal hypoglycaemic events (OR 0.74, 95% CI 0.56, 0.97; P = 0.03). No difference was observed regarding serious adverse events between the two groups.
CONCLUSION
The once-weekly basal insulin analogues seem to be at least equally efficient in glycaemic management and safe compared to once-daily injections in people with T2DM. Phase 4 RCTs are expected to shed further light on the effectiveness and safety of once-weekly insulin therapy over the long term.
Topics: Humans; Insulin; Glycated Hemoglobin; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Hypoglycemia; Insulin, Regular, Human
PubMed: 37667676
DOI: 10.1111/dom.15259