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Complementary Therapies in Clinical... Aug 2023Effects of ketone supplements as well as relevant dose-response relationships and time effects on blood β-hydroxybutyrate (BHB), glucose and insulin are controversial. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Effects of ketone supplements as well as relevant dose-response relationships and time effects on blood β-hydroxybutyrate (BHB), glucose and insulin are controversial.
OBJECTIVE
This study aimed to summarize the existing evidence and synthesize the results, and demonstrate underlying dose-response relationships as well as sustained time effects.
METHODS
Medline, Web of Science, Embase, and Cochrane Central Register of Controlled Trials were searched for relevant randomized crossover/parallel studies published until 25th November 2022. Three-level meta-analysis compared the acute effects of exogenous ketone supplementation and placebo in regulating blood parameters, with Hedge's g used as measure of effect size. Effects of potential moderators were explored through multilevel regression models. Dose-response and time-effect models were established via fractional polynomial regression.
RESULTS
The meta-analysis with 327 data points from 30 studies (408 participants) indicated that exogenous ketones led to a significant increase in blood BHB (Hedge's g = 1.4994, 95% CI [1.2648, 1.7340]), reduction in glucose (Hedge's g = -0.3796, 95% CI [-0.4550, -0.3041]), and elevation in insulin of non-athlete healthy population (Hedge's g = 0.1214, 95%CI [0.0582, 0.3011]), as well as insignificant change in insulin of obesity and prediabetes. Nonlinear dose-response relationship between ketone dosage and blood parameter change was observed in some time intervals for BHB (30-60 min; >120 min) and insulin (30-60 min; 90-120 min), with linear relationship observed for glucose (>120 min). Nonlinear associations between time and blood parameter change were found in BHB (>550 mg/kg) and glucose (450-550 mg/kg), with linear relationship observed in BHB (≤250 mg/kg) and insulin (350-550 mg/kg).
CONCLUSION
Dose-response relationships and sustained time effects were observed in BHB, glucose and insulin following ketone supplementation. Glucose-lowering effect without increasing insulin load among population of obesity and prediabetes was of remarkable clinical implication.
REGISTRY AND REGISTRY NUMBER
PROSPERO (CRD42022360620).
Topics: Humans; Insulin; Glucose; 3-Hydroxybutyric Acid; Ketones; Prediabetic State; Obesity; Dietary Supplements; Blood Glucose
PubMed: 37327753
DOI: 10.1016/j.ctcp.2023.101774 -
Islets Mar 2017The maintenance of viable and functional pancreatic islets is crucial for successful islet transplantation from brain-dead donors. To overcome islet quality loss during... (Meta-Analysis)
Meta-Analysis Review
The maintenance of viable and functional pancreatic islets is crucial for successful islet transplantation from brain-dead donors. To overcome islet quality loss during culture, some studies have co-cultured islets with mesenchymal stem/stromal cells (MSC). However, it is still uncertain if MSC-secreted factors are enough to improve islet quality or if a physical contact between MSCs and islets is needed. Therefore, we performed a systematic review and meta-analysis to clarify the effect of different culture contact systems of islets with MSCs on viability and insulin secretion outcomes. Pubmed and Embase were searched. Twenty studies fulfilled the eligibility criteria and were included in the qualitative synthesis and/or meta-analysis. For both outcomes, pooled weighted mean differences (WMD) between islet cultured alone (control group) and the co-culture condition were calculated. Viability mean was higher in islets co-cultured with MSCs compared with islet cultured alone [WMD = 18.08 (95% CI 12.59-23.57)]. The improvement in viability was higher in islets co-cultured in indirect or mixed contact with MSCs than in direct physical contact (P <0.001). Moreover, the mean of insulin stimulation index (ISI) was higher in islets from co-culture condition compared with islet cultured alone [WMD = 0.83 (95% CI 0.54-1.13)], independently of contact system. Results from the studies that were analyzed only qualitatively are in accordance with meta-analysis data. Co-culture of islets with MSCs has the potential for protecting islets from injury during culture period. Moreover, culture time appears to influence the beneficial effect of different methods of co-culture on viability and function of islets.
Topics: Animals; Coculture Techniques; Humans; Insulin; Insulin Secretion; Islets of Langerhans; Mesenchymal Stem Cells
PubMed: 28151049
DOI: 10.1080/19382014.2017.1286434 -
Current Drug Safety Nov 2013An association of insulin use and risk of cancer has been reported but evidence is conflicting and methodological issues have been identified. (Review)
Review
BACKGROUND
An association of insulin use and risk of cancer has been reported but evidence is conflicting and methodological issues have been identified.
OBJECTIVE
To summarize results regarding insulin use and cancer risk by a systematic review and meta-analysis of cohort and case-control studies examining risk of cancer associated with insulin use in patients with diabetes.
DATA SOURCES
Systematic literature search in 5 databases: PubMed, Embase, Web of Science, Scopus and Cochrane Library. STUDY ELIGIBILITY CRITERIA (PICOS):
POPULATION
diabetes patients.
EXPOSURE
Users of any exogenous insulin. Comparison: Diabetes patients with or without use of antidiabetic drugs.
OUTCOME
Any incident cancer.
STUDY DESIGN
Cohort and case-control studies.
RESULTS
42 eligible studies examined risk of any cancer and 27 site-specific cancers. Results of individual studies were heterogeneous. Meta-analyses were significant for: Insulin vs No Insulin: Increased risk for pancreas, liver, kidney, stomach and respiratory cancer, decreased risk for prostate cancer. Insulin vs Non-Insulin Antidiabetics: Increased risk for any, pancreatic and colorectal cancer. Glargine vs Non-Glargine Insulin: Increased risk for breast cancer, decreased risk for colon cancer.
LIMITATIONS
Few studies available for most cancer sites and exposure contrasts, and few assess effect of dose and duration of exposure. Methodological issues in several studies. Availability of confounders.
CONCLUSIONS
Insulin use was associated with risk of cancer at several sites. Cautious interpretation of results is warranted as methodological issues and limitations in several of the included studies have been identified. Choice of study design may have a profound effect on estimated cancer risk.
Topics: Breast Neoplasms; Case-Control Studies; Cohort Studies; Colorectal Neoplasms; Diabetes Mellitus; Female; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Neoplasms; Observational Studies as Topic; Publication Bias; Registries; Research Design
PubMed: 24215311
DOI: 10.2174/15680266113136660067 -
Advances in Therapy May 2023The objective of this systematic literature review was to evaluate the available literature concerning the clinical, economic, and patient-reported benefits of insulin...
INTRODUCTION
The objective of this systematic literature review was to evaluate the available literature concerning the clinical, economic, and patient-reported benefits of insulin pen platforms, including connected insulin pens/caps/sleeves and insulin platforms, as well as mobile apps capable of receiving near real-time insulin dosing information.
METHODS
Medline and Embase databases and the Cochrane Library were searched for published literature between January 2015 and May 2021, and manual searches for conference abstracts from 2018 to May 2021 were performed. These searches were supplemented by internet searches for relevant literature and clinical trials. Study selection involved the population, intervention, comparator, outcomes, time frame, and study design outline. Included studies investigated connected insulin systems or connected caps/sleeves enabling pens to be connected, or apps able to connect to these systems, in individuals of all ages with type 1 or type 2 diabetes mellitus.
RESULTS
Searches identified a total of 26 publications (mostly observational studies and conference abstracts) for inclusion, representing ten unique, predominantly small studies. Evidence in this field is still in its early stages, and only two randomized controlled trials met our inclusion criteria. Available results showed that connected insulin pens and their systems potentially helped reduce suboptimal insulin use and may therefore improve glycemic control. Satisfaction of people with diabetes with the technologies used was high, and economic benefits were noted. Features of effective connected insulin pen devices include simplicity of use and data upload/sharing, useful "point-of-care" alerts, and simple and understandable data presentation to facilitate more effective consultations.
CONCLUSIONS
Connected insulin pen systems could be increasingly considered as part of routine clinical care for insulin-treated persons with diabetes who must manage the complexity of their daily insulin routine. Future research focusing on the way data obtained from these devices can be most effectively used alongside other information is urgently needed.
Topics: Humans; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Randomized Controlled Trials as Topic; Insulin; Hypoglycemic Agents; Mobile Applications; Point-of-Care Systems; Injections, Subcutaneous; Cost-Benefit Analysis
PubMed: 36928495
DOI: 10.1007/s12325-023-02478-1 -
The Cochrane Database of Systematic... Apr 2013Pancreatic resections are associated with high morbidity (30% to 60%) and mortality (5%). Synthetic analogues of somatostatin are advocated by some surgeons to reduce... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Pancreatic resections are associated with high morbidity (30% to 60%) and mortality (5%). Synthetic analogues of somatostatin are advocated by some surgeons to reduce complications following pancreatic surgery; however, their use is controversial.
OBJECTIVES
To determine whether prophylactic somatostatin analogues should be used routinely in pancreatic surgery.
SEARCH METHODS
We searched the Cochrane Upper Gastrointestinal and Pancreatic Diseases Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 1), MEDLINE, EMBASE and Science Citation Index Expanded to February 2013.
SELECTION CRITERIA
We included randomised controlled trials comparing prophylactic somatostatin or one of its analogues versus no drug or placebo during pancreatic surgery (irrespective of language or publication status).
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed trials for inclusion and independently extracted data. We analysed data with both the fixed-effect and random-effects models using Review Manager (RevMan). We calculated the risk ratio (RR), mean difference (MD) or standardised mean difference (SMD) with 95% confidence intervals (CI) based on an intention-to-treat or available case analysis. When it was not possible to perform either of the above, we performed a per protocol analysis.
MAIN RESULTS
We identified 21 trials (19 trials of high risk of bias) involving 2348 people. There was no significant difference in the perioperative mortality (RR 0.80; 95% CI 0.56 to 1.16; n = 2210) or the number of people with drug-related adverse effects between the two groups (RR 2.09; 95% CI 0.83 to 5.24; n = 1199). Quality of life was not reported in any of the trials. The overall number of participants with postoperative complications was significantly lower in the somatostatin analogue group (RR 0.70; 95% CI 0.61 to 0.80; n = 1903) but there was no significant difference in the re-operation rate (RR 1.26; 95% CI 0.58 to 2.70; n = 687) or hospital stay (MD -1.29 days; 95% CI -2.60 to 0.03; n = 1314) between the groups. The incidence of pancreatic fistula was lower in the somatostatin analogue group (RR 0.66; 95% CI 0.55 to 0.79; n = 2206). The proportion of these fistulas that were clinically significant was not mentioned in most trials. On inclusion of trials that clearly distinguished clinically significant fistulas, there was no significant difference between the two groups (RR 0.69; 95% CI 0.38 to 1.28; n = 292).
AUTHORS' CONCLUSIONS
Somatostatin analogues may reduce perioperative complications but do not reduce perioperative mortality. Further adequately powered trials with low risk of bias are necessary. Based on the current available evidence, somatostatin and its analogues are recommended for routine use in people undergoing pancreatic resection.
Topics: Gastrointestinal Agents; Humans; Length of Stay; Octreotide; Pancreas; Pancreatectomy; Pancreatic Diseases; Pancreatic Fistula; Pancreaticoduodenectomy; Postoperative Complications; Publication Bias; Randomized Controlled Trials as Topic; Reoperation; Sepsis; Somatostatin
PubMed: 23633353
DOI: 10.1002/14651858.CD008370.pub3 -
The Cochrane Database of Systematic... Jun 2012Pancreatic resections are associated with high morbidity (30% to 60%) and mortality (5%). Synthetic analogues of somatostatin are advocated by some surgeons to reduce... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Pancreatic resections are associated with high morbidity (30% to 60%) and mortality (5%). Synthetic analogues of somatostatin are advocated by some surgeons to reduce complications following pancreatic surgery, however their use is controversial.
OBJECTIVES
To determine whether prophylactic somatostatin analogues should be used routinely in pancreatic surgery.
SEARCH METHODS
We searched the Cochrane Upper Gastrointestinal and Pancreatic Diseases Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 12), MEDLINE, EMBASE and Science Citation Index Expanded to December 2011.
SELECTION CRITERIA
We included randomised controlled trials comparing prophylactic somatostatin or one of its analogues versus no drug or placebo during pancreatic surgery (irrespective of language or publication status).
DATA COLLECTION AND ANALYSIS
Two authors independently assessed trials for inclusion and independently extracted data. We analysed data with both the fixed-effect and random-effects models using Review Manager (RevMan). We calculated the risk ratio (RR), mean difference (MD) or standardised mean difference (SMD) with 95% confidence intervals (CI) based on an intention-to-treat or available case analysis. When it was not possible to perform either of the above, we performed per protocol analysis.
MAIN RESULTS
We identified 19 trials (17 trials of high risk of bias) involving 2245 patients. There was no significant difference in the perioperative mortality (RR 0.80; 95% CI 0.56 to 1.16; N = 2210) or the number of patients with drug-related adverse effects between the two groups (RR 2.09; 95% CI 0.83 to 5.24; N = 1199). Quality of life was not reported in any of the trials. The overall number of patients with postoperative complications was significantly lower in the somatostatin analogue group (RR 0.69; 95% CI 0.60 to 0.79; N = 1858) but there was no significant difference in the re-operation rate (RR 1.26; 95% CI 0.58 to 2.70; N = 687) or hospital stay (MD -1.04 days; 95% CI -2.54 to 0.46; N = 1269) between the groups. The incidence of pancreatic fistula was lower in the somatostatin analogue group (RR 0.63; 95% CI 0.52 to 0.77; N = 2161). The proportion of these fistulas that were clinically significant was not mentioned in most trials. On inclusion of trials that clearly distinguished clinically significant fistulas, there was no significant difference between the two groups (RR 0.69; 95% CI 0.34 to 1.41; N = 247).
AUTHORS' CONCLUSIONS
Somatostatin analogues may reduce perioperative complications but do not reduce perioperative mortality. Further adequately powered trials with low risk of bias are necessary. Based on the current available evidence, somatostatin and its analogues are recommended for routine use in patients undergoing pancreatic resection.
Topics: Gastrointestinal Agents; Humans; Length of Stay; Octreotide; Pancreas; Pancreatectomy; Pancreatic Diseases; Pancreatic Fistula; Pancreaticoduodenectomy; Postoperative Complications; Publication Bias; Randomized Controlled Trials as Topic; Sepsis; Somatostatin
PubMed: 22696379
DOI: 10.1002/14651858.CD008370.pub2 -
The British Journal of Nutrition Jun 2023Although previous studies suggested the protective effect of Zn for type 2 diabetes (T2D), the unitary causal effect remains inconclusive. We investigated the causal... (Meta-Analysis)
Meta-Analysis Review
Triangulating evidence for the causal impact of single-intervention zinc supplement on glycaemic control for type 2 diabetes: systematic review and meta-analysis of randomised controlled trial and two-sample Mendelian randomisation.
Although previous studies suggested the protective effect of Zn for type 2 diabetes (T2D), the unitary causal effect remains inconclusive. We investigated the causal effect of Zn as a single intervention on glycaemic control for T2D, using a systematic review of randomised controlled trials and two-sample Mendelian randomisation (MR). Four primary outcomes were identified: fasting blood glucose/fasting glucose, HbA1c, homeostatic model assessment for insulin resistance (HOMA-IR) and serum insulin/fasting insulin level. In the systematic review, four databases were searched until June 2021. Studies, in which participants had T2D and intervention did not comprise another co-supplement, were included. Results were synthesised through the random-effects meta-analysis. In the two-sample MR, we used single-nucleotide polymorphisms (SNP) from MR-base, strongly related to Zn supplements, to infer the relationship causally, but not specified T2D. In the systematic review and meta-analysis, fourteen trials were included with overall 897 participants initially. The Zn supplement led to a significant reduction in the post-trial mean of fasting blood glucose (mean difference (MD): -26·52 mg/dl, 95 % CI (-35·13, -17·91)), HbA1c (MD: -0·52 %, 95 % CI: (-0·90, -0·13)) and HOMA-IR (MD: -1·65, 95 % CI (-2·62, -0·68)), compared to the control group. In the two-sample MR, Zn supplement with two SNP reduced the fasting glucose (inverse-variance weighted coefficient: -2·04 mmol/l, 95 % CI (-3·26, -0·83)). From the two methods, Zn supplementation alone may causally improve glycaemic control among T2D patients. The findings are limited by power from the small number of studies and SNP included in the systematic review and two-sample MR analysis, respectively.
Topics: Humans; Diabetes Mellitus, Type 2; Blood Glucose; Glycated Hemoglobin; Risk Factors; Glycemic Control; Insulin Resistance; Insulins; Zinc; Insulin; Randomized Controlled Trials as Topic
PubMed: 35946077
DOI: 10.1017/S0007114522002616 -
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 -
Journal of Cosmetic Dermatology Nov 2022This study aimed to evaluate the Standardized Mean Difference (SMD) of insulin resistance parameters in women with IH, compared to healthy and polycystic ovary syndrome... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
This study aimed to evaluate the Standardized Mean Difference (SMD) of insulin resistance parameters in women with IH, compared to healthy and polycystic ovary syndrome (PCOS) controls.
MATERIALS AND METHODS
PubMed, Scopus, Web of Sciences, and Embase were searched for retrieving studies published up to November 2021 investigating the insulin resistance parameters in women with IH, compared to control groups. Meta-regression and subgroup analysis were conducted to evaluate the effect of potential confounders, such as age, BMI, and study design.
RESULTS
A meta-analysis of 20 studies revealed that higher SMDs of fasting insulin (SMD: 0.58; 95% CI: 0.10, 1.06), HOMA-IR (SMD: 0.53; 95% CI: 0.09, 0.97), and FBS levels (SMD: 0.11; 95% CI: 0.03, 0.19) in women with IH than healthy. It also showed that the SMD of HOMA-IR was significantly lower in women with IH than PCOS patients (SMD: -0.49; 95% CI: -0.88, -0.09). A subgroup analysis of cross-sectional studies showed higher SMDs of fasting insulin (SMD: 0.86; 95% CI: 0.05, 1.68), HOMA-IR (SMD: 0.83; 95% CI: 0.01, 1.64), and FBS levels (SMD: 0.14; 95% CI: 0.00, 0.28) in women with IH than healthy, whereas there was no difference in the SMD of these metabolic parameters between IH and PCOS groups, except for SMD of HOMA-IR (SMD: -0.22; 95% CI: -0.42, -0.02).
CONCLUSIONS
The results of the study demonstrate that insulin resistance parameters are related to IH, although insulin resistance values in women with IH are not as high as in patients with PCOS. According to the results of the study, measuring these metabolic parameters can be beneficial to evaluate all hirsute women with IH.
Topics: Female; Humans; Hirsutism; Insulin Resistance; Cross-Sectional Studies; Polycystic Ovary Syndrome; Insulin
PubMed: 35531788
DOI: 10.1111/jocd.15070 -
Nutrients May 2022To assess the relationship between fat mass percentage (FMP) and glucose metabolism in children aged 0−18 years we performed a systematic review of the literature on... (Meta-Analysis)
Meta-Analysis Review
To assess the relationship between fat mass percentage (FMP) and glucose metabolism in children aged 0−18 years we performed a systematic review of the literature on Medline/PubMed, SinoMed, Embase and Cochrane Library using the PRISMA 2020 guidelines up to 12 October 2021 for observational studies that assessed the relationship of FMP and glucose metabolism. Twenty studies with 18,576 individuals were included in the meta-analysis. The results showed that FMP was significantly associated with fasting plasma glucose (FPG) (r = 0.08, 95% confidence interval (CI): 0.04−0.13, p < 0.001), fasting plasma insulin (INS) (r = 0.48, 95% CI: 0.37−0.57, p < 0.001), and homeostasis model assessment (HOMA)- insulin resistance (IR) (r = 0.44, 95% CI: 0.33−0.53, p < 0.001). The subgroup analysis according to country or overweight and obesity indicated that these associations remained significant between FMP and INS or HOMA-IR. Our results demonstrated that there is a positive relationship between FMP and FPG. Moreover, subgroup analysis according to country or overweight and obesity indicated that FMP is significantly associated with INS and HOMA-IR. This is the first known systematic review and meta-analysis to determine the associations of FMP with glucose metabolism in children and adolescents.
Topics: Adolescent; Blood Glucose; Child; Glucose; Humans; Insulin; Insulin Resistance; Obesity; Overweight
PubMed: 35684072
DOI: 10.3390/nu14112272