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Diabetes & Metabolic Syndrome Apr 2023We aimed to summarise the existing literature on insulin dose titration in gestation diabetes.
BACKGROUND AND AIMS
We aimed to summarise the existing literature on insulin dose titration in gestation diabetes.
METHODS
Databases: Medline, EMBASE, CENTRAL and CINAHL were systematically searched for trials and observational studies comparing insulin titration strategies in gestational diabetes.
RESULTS
No trials comparing insulin dose titration strategies were identified. Only one small (n = 111) observational study was included. In this study, patient-led daily basal insulin titration was associated with higher insulin doses, tighter glycaemic control, and lower birthweight, vs weekly clinician-led titration.
CONCLUSIONS
There is a paucity of evidence to support optimal insulin titration in gestational diabetes. Randomized trials are required.
Topics: Pregnancy; Female; Humans; Insulin; Diabetes, Gestational; Hypoglycemic Agents; Pregnancy in Diabetics; Birth Weight; Diabetes Mellitus, Type 2; Observational Studies as Topic
PubMed: 36966543
DOI: 10.1016/j.dsx.2023.102746 -
European Journal of Pharmacology May 2023To update the evidence about the diabetogenic effect of statins. (Meta-Analysis)
Meta-Analysis Review
AIMS
To update the evidence about the diabetogenic effect of statins.
METHODS
We searched for randomized-controlled trials reporting the effects of statin therapy on glycosylated hemoglobin (HbA1c) and/or homeostatic model insulin resistance (i.e., HOMA-IR) as indexes of diabetes. Studies were classified between the ones testing normal vs individuals with already altered glycemic control (HbA1c ≥ 6.5%; and HOMA-IR ≥ 2.15). Furthermore, studies were separated by statin type and dosage prescribed. Data are presented as mean difference (MD) and 95% confidence intervals.
RESULTS
A total of 67 studies were included in the analysis (>25,000 individuals). In individuals with altered glycemic control, statins increased HbA1c levels (MD 0.21%, 95% CI 0.16-to-0.25) and HOMA-IR index (MD 0.31, 95% CI 0.24-to-0.38). In individuals with normal glycemic control, statin increased HbA1c (MD 1.33%, 95% CI 1.31-to-1.35) and HOMA-IR (MD 0.49, 95% CI 0.41-to-0.58) in comparison to the placebo groups. The dose or type of statins did not modulate the diabetogenic effect.
CONCLUSIONS
Statins, slightly but significantly raise indexes of diabetes in individuals with adequate or altered glycemic control. The diabetogenic effect does not seem to be influenced by the type or dosage of statin prescribed.
Topics: Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Glycated Hemoglobin; Insulin Resistance; Glycemic Control; Diabetes Mellitus; Blood Glucose; Insulin; Diabetes Mellitus, Type 2
PubMed: 36965747
DOI: 10.1016/j.ejphar.2023.175672 -
Canadian Journal of Diabetes Jun 2023Our aim in this study was to compare the efficacy and safety of commercially available fixed-ratio combinations (FRCs) of glucagon-like peptide-1 receptor agonists... (Meta-Analysis)
Meta-Analysis
Comparison of Efficacy and Safety of Commercially Available Fixed-Ratio Combinations of Insulin Degludec/Liraglutide and Insulin Glargine/Lixisenatide: A Network Meta-analysis.
OBJECTIVES
Our aim in this study was to compare the efficacy and safety of commercially available fixed-ratio combinations (FRCs) of glucagon-like peptide-1 receptor agonists (GLP-1RAs) and basal insulins by a network meta-analysis of randomized controlled trials (RCTs) of people with type 2 diabetes.
METHODS
We present a systematic review and network meta-analyses of RCTs of individuals with type 2 diabetes randomized to FRCs or to their components for ≥24 weeks. All reports were obtained from PubMed or ClinicalTrials.gov up to February 28, 2022. The primary outcome was glycated hemoglobin (A1C) level attained. Secondary outcomes included fasting plasma glucose, change in body weight, and incident hypoglycemia. Treatment effects were estimated as mean difference (MD) and standard error (SE), or as odds ratio (OR) with 95% confidence interval (CI) using the fixed combination of insulin glargine 100 IU/mL and lixisenatide (iGlarLixi) as reference.
RESULTS
We included 29 RCTs from among the 1,404 articles identified. No direct comparisons between FRCs were found. After excluding some insulin-capped trials to reach model consistency, both FRCs were more efficacious regarding A1C than their components, but no difference between FRCs was found (MD, -0.10%; SE, 0.10%). The effect of the fixed combination of insulin degludec and liraglutide (IDegLira) (MD, -0.47 mmol/L; SE, 0.24 mmol/L) and basal insulins was similar to that of iGlarLixi (reference) on fasting glucose, whereas GLP-1RAs had lower efficacy than iGlarLixi. Weight gain was lower with GLP-1RAs and IDegLira (MD, -0.72 kg; SE, 0.32 kg) than with iGlarLixi (reference) and higher with basal insulins. Incident hypoglycemia (based on different definitions) was least frequent with GLP-1RAs, followed by IDegLira (OR, 0.78; 95% CI, 0.39 to 1.57), iGlarLixi (reference), and basal insulins.
CONCLUSIONS
For A1C, both FRCs were more efficacious over their individual components, with similar efficacies of the 2 FRCs.
Topics: Humans; Liraglutide; Insulin Glargine; Network Meta-Analysis; Glycated Hemoglobin; Blood Glucose; Drug Combinations; Hypoglycemic Agents; Diabetes Mellitus, Type 2; Hypoglycemia; Randomized Controlled Trials as Topic
PubMed: 36963632
DOI: 10.1016/j.jcjd.2023.03.002 -
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 -
International Journal of Molecular... Mar 2023Meningioma is the most frequent brain tumor, and the incidence is ever-increasing. Though often benign and slow growth, recurrence rates are substantial and today's...
Meningioma is the most frequent brain tumor, and the incidence is ever-increasing. Though often benign and slow growth, recurrence rates are substantial and today's surgical and radiation-based treatment are not without complications. No drugs specific for meningiomas are hitherto approved and patients with inoperable or recurrent meningioma are left with few treatment options. Somatostatin receptors are previously detected in meningiomas and may inhibit growth when stimulated by somatostatin. Hence, somatostatin analogs could provide a targeted drug therapy. The aim of this study was to compile the current insights of somatostatin analogs for patients with meningioma. This paper adheres to the PRISMA extension for Scoping Reviews. A systematic search was conducted in the search databases PubMed, Embase via Ovid, and Web of Science. Seventeen papers adhered to the inclusion and exclusion criteria, and critical appraisal was conducted. The overall quality of evidence is low, as none of the studies were randomized or controlled. Various efficacy of somatostatin analogs is reported, and adverse effects are sparse. Due to the beneficial effects reported by some studies, somatostatin analogs may offer a novel last-option treatment for severely ill-patients. Nonetheless, only a controlled study, preferably a randomized clinical trial, could clarify the efficacy of somatostatin analogs.
Topics: Humans; Meningeal Neoplasms; Meningioma; Neoplasm Recurrence, Local; Octreotide; Randomized Controlled Trials as Topic; Receptors, Somatostatin; Somatostatin
PubMed: 36902224
DOI: 10.3390/ijms24054793 -
Nutrients Feb 2023There has been an emerging concern that non-nutritive sweeteners (NNS) can increase the risk of cardiometabolic disease. Much of the attention has focused on acute... (Meta-Analysis)
Meta-Analysis
There has been an emerging concern that non-nutritive sweeteners (NNS) can increase the risk of cardiometabolic disease. Much of the attention has focused on acute metabolic and endocrine responses to NNS. To examine whether these mechanisms are operational under real-world scenarios, we conducted a systematic review and network meta-analysis of acute trials comparing the effects of non-nutritive sweetened beverages (NNS beverages) with water and sugar-sweetened beverages (SSBs) in humans. MEDLINE, EMBASE, and The Cochrane Library were searched through to January 15, 2022. We included acute, single-exposure, randomized, and non-randomized, clinical trials in humans, regardless of health status. Three patterns of intake were examined: (1) uncoupling interventions, where NNS beverages were consumed alone without added energy or nutrients; (2) coupling interventions, where NNS beverages were consumed together with added energy and nutrients as carbohydrates; and (3) delayed coupling interventions, where NNS beverages were consumed as a preload prior to added energy and nutrients as carbohydrates. The primary outcome was a 2 h incremental area under the curve (iAUC) for blood glucose concentration. Secondary outcomes included 2 h iAUC for insulin, glucagon-like peptide 1 (GLP-1), gastric inhibitory polypeptide (GIP), peptide YY (PYY), ghrelin, leptin, and glucagon concentrations. Network meta-analysis and confidence in the network meta-analysis (CINeMA) were conducted in R-studio and CINeMA, respectively. Thirty-six trials involving 472 predominantly healthy participants were included. Trials examined a variety of single NNS (acesulfame potassium, aspartame, cyclamate, saccharin, stevia, and sucralose) and NNS blends (acesulfame potassium + aspartame, acesulfame potassium + sucralose, acesulfame potassium + aspartame + cyclamate, and acesulfame potassium + aspartame + sucralose), along with matched water/unsweetened controls and SSBs sweetened with various caloric sugars (glucose, sucrose, and fructose). In uncoupling interventions, NNS beverages (single or blends) had no effect on postprandial glucose, insulin, GLP-1, GIP, PYY, ghrelin, and glucagon responses similar to water controls (generally, low to moderate confidence), whereas SSBs sweetened with caloric sugars (glucose and sucrose) increased postprandial glucose, insulin, GLP-1, and GIP responses with no differences in postprandial ghrelin and glucagon responses (generally, low to moderate confidence). In coupling and delayed coupling interventions, NNS beverages had no postprandial glucose and endocrine effects similar to controls (generally, low to moderate confidence). The available evidence suggests that NNS beverages sweetened with single or blends of NNS have no acute metabolic and endocrine effects, similar to water. These findings provide support for NNS beverages as an alternative replacement strategy for SSBs in the acute postprandial setting.
Topics: Humans; Sugar-Sweetened Beverages; Aspartame; Ghrelin; Glucagon; Cyclamates; Network Meta-Analysis; Blood Glucose; Glucose; Non-Nutritive Sweeteners; Beverages; Sucrose; Insulin; Sugars; Glucagon-Like Peptide 1; Water
PubMed: 36839408
DOI: 10.3390/nu15041050 -
Cells Feb 2023Diabetic and obese patients have a high prevalence of non-alcoholic fatty liver disease (NAFLD). This condition groups a spectrum of conditions varying from simple... (Review)
Review
Diabetic and obese patients have a high prevalence of non-alcoholic fatty liver disease (NAFLD). This condition groups a spectrum of conditions varying from simple steatosis to non-alcoholic steatohepatitis (NASH), with or without fibrosis. Multiple factors are involved in the development of NAFLD. However, details about its pathogenesis and factors that promote the progression to NASH are still missing. Growth hormone (GH) and insulin-like growth factor 1 (IGF-1) regulate metabolic, immune, and hepatic stellate cell functions. Increasing evidence suggests they may have roles in the progression from NAFLD to NASH. Following the PRISMA reporting guidelines, we conducted a systematic review to evaluate all clinical and experimental studies published in the literature correlating GH and IGF-1 to inflammation and fibrosis in NAFLD and NASH. Our results showed that GH and IGF-1 have a fundamental role in the pathogenesis of NASH, acting in slightly different ways to produce a synergic effect. Indeed, GH may mediate its protective effect in the pathogenesis of NASH by regulating lipogenesis pathways, while IGF-1 has the same effect by regulating cholesterol transport. Therefore, they could be used as therapeutic strategies in preventing NAFLD progression to NASH.
Topics: Humans; Non-alcoholic Fatty Liver Disease; Growth Hormone; Insulin-Like Growth Factor I; Insulin; Liver Cirrhosis; Human Growth Hormone; Insulin, Regular, Human; Hepatitis
PubMed: 36831184
DOI: 10.3390/cells12040517 -
International Journal of Obesity (2005) May 2023The effect of exercise training on whole-body insulin sensitivity has not been systematically summarized. We aimed to summarize the data from randomized controlled... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND OBJECTIVE
The effect of exercise training on whole-body insulin sensitivity has not been systematically summarized. We aimed to summarize the data from randomized controlled trials evaluating the effect of exercise training on insulin action, in adults.
SUBJECTS
MEDLINE, EMBASE, and CENTRAL databases were searched until January 2021. Randomized controlled trials lasting ≥4 weeks, including adults, and evaluating the effect of exercise on insulin-stimulated glucose disposal measured using the hyperinsulinemic euglycemic clamp, were included.
METHODS
Three reviewers extracted summary data from published trials. The primary outcome was insulin-stimulated glucose disposal. Standardized weighted mean differences (SMD) in glucose disposal between intervention and control were compared. The PEDro scale was used to assess risk of bias.
RESULTS
We included 25 trials (36 interventions, N = 851). Exercise increased insulin-stimulated glucose disposal relative to control, SMD = 0.52 (95% confidence interval [CI]: 0.39, 0.65; p < 0.001; I = 47%) without significantly suppressing hepatic glucose production. In trials without isotopic tracers, exercise increased glucose disposal (SMD = 0.63; 95% CI: 0.48, 0.77; p < 0.001, I = 55%). In trials with isotopic tracers, exercise increased glucose disposal only when tracers were added to the exogenous glucose used for clamping (SMD = 0.34; 95% CI: 0.03, 0.66, p = 0.034. I = 0%). In a meta-regression model including aerobic exercise, weight change, and tracer technique, only percent weight change explained between trial heterogeneity (β = 0.069; 95% CI: 0.005, 0.013). The PEDro rating indicated relatively low risk of bias (5.8 ± 0.22).
CONCLUSIONS
Exercise training for at least four weeks significantly increases insulin-stimulated glucose disposal. Weight loss maximizes the effect and may be needed to improve hepatic insulin sensitivity. Differences in tracer methodology contribute to divergent outcomes and should be considered when assessing conclusions from research examining the effect of exercise on insulin action.
REGISTRATION
PROSPERO (CRD42019124381).
Topics: Adult; Humans; Insulin; Glucose; Insulin Resistance; Randomized Controlled Trials as Topic; Exercise
PubMed: 36828899
DOI: 10.1038/s41366-023-01283-8 -
Advances in Nutrition (Bethesda, Md.) Jan 2023Bread is a major source of grain-derived carbohydrates worldwide. High intakes of refined grains, low in dietary fiber and high in glycemic index, are linked with... (Meta-Analysis)
Meta-Analysis Review
Bread is a major source of grain-derived carbohydrates worldwide. High intakes of refined grains, low in dietary fiber and high in glycemic index, are linked with increased risk for type 2 diabetes mellitus (T2DM) and other chronic diseases. Hence, improvements in the composition of bread could influence population health. This systematic review evaluated the effect of regular consumption of reformulated breads on glycemic control among healthy adults, adults at cardiometabolic risk or with manifest T2DM. A literature search was performed using MEDLINE, Embase, Web of Science and the Cochrane Central Register of Controlled Trials. Eligible studies employed a bread intervention (≥2 wk) in adults (healthy, at cardiometabolic risk or manifest T2DM) and reported glycemic outcomes (fasting blood glucose, fasting insulin, HOMA-IR, HbA1c, and postprandial glucose responses). Data were pooled using generic inverse variance with random-effects model and presented as mean difference (MD) or standardized MD between treatments with 95% CIs. Twenty-two studies met the inclusion criteria (n = 1037 participants). Compared with "regular" or comparator bread, consumption of reformulated intervention breads yielded lower fasting blood glucose concentrations (MD: -0.21 mmol/L; 95% CI: -0.38, -0.03; I = 88%, moderate certainty of evidence), yet no differences in fasting insulin (MD: -1.59 pmol/L; 95% CI: -5.78, 2.59; I = 38%, moderate certainty of evidence), HOMA-IR (MD: -0.09; 95% CI: -0.35, 0.23; I = 60%, moderate certainty of evidence), HbA1c (MD: -0.14; 95% CI: -0.39, 0.10; I = 56%, very low certainty of evidence), or postprandial glucose response (SMD: -0.46; 95% CI: -1.28, 0.36; I = 74%, low certainty of evidence). Subgroup analyses revealed a beneficial effect for fasting blood glucose only among people with T2DM (low certainty of evidence). Our findings suggest a beneficial effect of reformulated breads high in dietary fiber, whole grains, and/or functional ingredients on fasting blood glucose concentrations in adults, primarily among those with T2DM. This trial was registered at PROSPERO as CRD42020205458.
Topics: Adult; Humans; Diabetes Mellitus, Type 2; Bread; Blood Glucose; Glycated Hemoglobin; Randomized Controlled Trials as Topic; Insulin; Dietary Fiber; Cardiovascular Diseases
PubMed: 36811592
DOI: 10.1016/j.advnut.2022.10.008 -
European Journal of Pediatrics May 2023Hybrid closed loop (HCL) systems are the combination of a pump for insulin delivery and a glucose sensor for continuous glucose monitoring. These systems are managed by... (Review)
Review
Hybrid closed loop (HCL) systems are the combination of a pump for insulin delivery and a glucose sensor for continuous glucose monitoring. These systems are managed by an algorithm, which delivers insulin on the basis of the interstitial glucose levels. The MiniMed™ 670G system was the first HCL system available for clinical purpose. In this paper, we reviewed the literature about metabolic and psychological outcomes in children, adolescents and young adults with type 1 diabetes treated with MiniMed™ 670G. Only 30 papers responded to the inclusion criteria and thus were considered. All the papers show that the system is safe and effective in managing glucose control. Metabolic outcomes are available up to 12 months of follow-up; longer study period are lacking. This HCL system may improve HbA1c up to 7.1% and time in range up to 73%. The time spent in hypoglycaemia is almost neglectable. Better improvement in blood glucose control is observed in patients with higher HbA1c at HCL system start and larger daily use of auto-mode functionality. Conclusion: The Medtronic MiniMed™ 670G is safe and well accepted, without any increase in the burden for patients. Some papers report an improvement in the psychological outcomes, but other papers do not confirm this finding. So far, it significantly improves the management of diabetes mellitus in children, adolescents and young adults. Proper training and support by the diabetes team are mandatory. Studies for a period longer than 1 year would be appreciated to better understand the potentiality of this system. What is Known: • The Medtronic MiniMed 670G is a hybrid closed loop system which combines a continuous glucose monitoring sensor with an insulin pump. • It has been the first hybrid closed loop system available for clinical purpose. Adequate training and patients support play a key role in diabetes management. What is New: • The Medtronic MiniMed 670G may improve HbA1c and CGM metrics up to 1-year of follow-up, but the improvement appears lower than advanced hybrid closed loop systems. This system is effective to prevent hypoglycaemia. • The psychosocial effects remain less understood in terms of improvement of psychosocial outcomes. The system has been considered to provide flexibility and independence by the patients and their caregivers. The workload required to use this system is perceived as a burden by the patients who decrease the use of auto-mode functionality over time.
Topics: Humans; Child; Adolescent; Young Adult; Hypoglycemic Agents; Glycated Hemoglobin; Blood Glucose; Blood Glucose Self-Monitoring; Diabetes Mellitus, Type 1; Insulin; Hypoglycemia
PubMed: 36809498
DOI: 10.1007/s00431-023-04833-4