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BMJ (Clinical Research Ed.) May 2022To investigate the association between gestational diabetes mellitus and adverse outcomes of pregnancy after adjustment for at least minimal confounding factors. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To investigate the association between gestational diabetes mellitus and adverse outcomes of pregnancy after adjustment for at least minimal confounding factors.
DESIGN
Systematic review and meta-analysis.
DATA SOURCES
Web of Science, PubMed, Medline, and Cochrane Database of Systematic Reviews, from 1 January 1990 to 1 November 2021.
REVIEW METHODS
Cohort studies and control arms of trials reporting complications of pregnancy in women with gestational diabetes mellitus were eligible for inclusion. Based on the use of insulin, studies were divided into three subgroups: no insulin use (patients never used insulin during the course of the disease), insulin use (different proportions of patients were treated with insulin), and insulin use not reported. Subgroup analyses were performed based on the status of the country (developed or developing), quality of the study, diagnostic criteria, and screening method. Meta-regression models were applied based on the proportion of patients who had received insulin.
RESULTS
156 studies with 7 506 061 pregnancies were included, and 50 (32.1%) showed a low or medium risk of bias. In studies with no insulin use, when adjusted for confounders, women with gestational diabetes mellitus had increased odds of caesarean section (odds ratio 1.16, 95% confidence interval 1.03 to 1.32), preterm delivery (1.51, 1.26 to 1.80), low one minute Apgar score (1.43, 1.01 to 2.03), macrosomia (1.70, 1.23 to 2.36), and infant born large for gestational age (1.57, 1.25 to 1.97). In studies with insulin use, when adjusted for confounders, the odds of having an infant large for gestational age (odds ratio 1.61, 1.09 to 2.37), or with respiratory distress syndrome (1.57, 1.19 to 2.08) or neonatal jaundice (1.28, 1.02 to 1.62), or requiring admission to the neonatal intensive care unit (2.29, 1.59 to 3.31), were higher in women with gestational diabetes mellitus than in those without diabetes. No clear evidence was found for differences in the odds of instrumental delivery, shoulder dystocia, postpartum haemorrhage, stillbirth, neonatal death, low five minute Apgar score, low birth weight, and small for gestational age between women with and without gestational diabetes mellitus after adjusting for confounders. Country status, adjustment for body mass index, and screening methods significantly contributed to heterogeneity between studies for several adverse outcomes of pregnancy.
CONCLUSIONS
When adjusted for confounders, gestational diabetes mellitus was significantly associated with pregnancy complications. The findings contribute to a more comprehensive understanding of the adverse outcomes of pregnancy related to gestational diabetes mellitus. Future primary studies should routinely consider adjusting for a more complete set of prognostic factors.
REVIEW REGISTRATION
PROSPERO CRD42021265837.
Topics: Cesarean Section; Diabetes, Gestational; Female; Fetal Macrosomia; Humans; Infant, Newborn; Insulin; Pregnancy; Pregnancy Complications; Pregnancy Outcome
PubMed: 35613728
DOI: 10.1136/bmj-2021-067946 -
Reproductive Biology and Endocrinology... Jan 2023Metformin is the gold standard insulin sensitizer, which is widely used to treat insulin resistance in polycystic ovary syndrome (PCOS). However, metformin may induce... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Metformin is the gold standard insulin sensitizer, which is widely used to treat insulin resistance in polycystic ovary syndrome (PCOS). However, metformin may induce gastrointestinal side effects.
OBJECTIVE
Inositols have long been debated as a potential alternative for metformin in treating PCOS. Therefore, the present systematic review aimed to evaluate the efficacy and safety of inositols in treating PCOS.
METHODS
The present systematic search was performed in CENTRAL, MEDLINE, and Embase from the inception until October 20th, 2021. Eligible randomized controlled trials (RCTs) included women diagnosed with PCOS and compared any inositols with metformin or placebo. Our primary outcome was cycle normalization, whereas secondary outcomes were body mass index (BMI), parameters of carbohydrate metabolism and clinical and laboratory hyperandrogenism. Results are reported as risk ratios or mean differences (MDs) with 95% confidence intervals (CIs).
RESULTS
Twenty-six RCTs were identified, including data of 1691 patients (806 inositol, 311 with placebo, and 509 metformin groups). In patients treated with inositols, the risk (CI: 1.13; 2.85) of having a regular menstrual cycle was found by 1.79 higher than in the case of placebo. Moreover, the inositols showed non-inferiority compared to metformin in this outcome. In the case of BMI (MD = -0.45; CI: -0.89; -0.02), free testosterone (MD = -0,41, CI: -0.69; -0.13), total testosterone (MD = -20.39, CI: -40.12; -0.66), androstenedione (MD = -0.69, CI: -1,16; -0.22), glucose (MD = -3.14; CI: -5.75; -0.54) levels and AUC insulin (MD = -2081.05, CI: -2745.32; -1416.78) inositol treatment induced greater decrease compared to placebo. Inositol increased sex-hormone-binding globulin significantly compared to placebo (MD = 32.06, CI:1.27; 62.85).
CONCLUSION
Inositol is an effective and safe treatment in PCOS. Moreover, inositols showed non-inferiority in most outcomes compared to the gold standard treatment; metformin.
TRIAL REGISTRATION
PROSPERO registration number: CRD42021283275.
Topics: Female; Humans; Polycystic Ovary Syndrome; Inositol; Hypoglycemic Agents; Randomized Controlled Trials as Topic; Metformin; Testosterone; Insulins
PubMed: 36703143
DOI: 10.1186/s12958-023-01055-z -
The Journal of Clinical Endocrinology... Oct 2020The effect of diet on insulin resistance (IR) in polycystic ovary syndrome (PCOS) is controversial. Thus, we conducted this systematic review and meta-analysis to... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The effect of diet on insulin resistance (IR) in polycystic ovary syndrome (PCOS) is controversial. Thus, we conducted this systematic review and meta-analysis to evaluate whether diet could reduce IR in women with PCOS while providing optimal and precise nutrition advice for clinical practice.
DESIGN
The search was conducted in 8 databases through June 30, 2019. The systematic review was performed following the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. A random-effects model was adopted to calculate the overall effects.
RESULTS
A total of 19 trials (1193 participants) were included. The analysis showed that diet was significantly related to improvements in IR and body composition (eg, homeostasis model assessment of insulin resistance, fasting insulin, fasting plasma glucose, body mass index [BMI], weight, and waist circumference) in PCOS patients. The Dietary Approaches to Stop Hypertension diet and calorie-restricted diets might be the optimal choices for reducing IR and improving body composition, respectively, in the PCOS population. Additionally, the effects were associated with the course of treatment. The longer the duration, the greater the improvement was. Compared with metformin, diet was also advantageous for weight loss (including BMI and weight) and had the same effects on insulin regulation.
CONCLUSION
Overall, our findings suggest that diet is an effective, acceptable and safe intervention for relieving IR, and professional dietary advice should be offered to all PCOS patients.
Topics: Blood Glucose; Body Mass Index; Caloric Restriction; Counseling; Dietary Approaches To Stop Hypertension; Dietary Services; Fasting; Female; Humans; Insulin; Insulin Resistance; Polycystic Ovary Syndrome; Time Factors; Treatment Outcome; Weight Loss
PubMed: 32621748
DOI: 10.1210/clinem/dgaa425 -
International Journal of Molecular... Nov 2022The prevalence of type 1 diabetes (T1D) is rising steadily. A potential contributor to the rise is vitamin D. In this systematic review, we examined the literature... (Review)
Review
The prevalence of type 1 diabetes (T1D) is rising steadily. A potential contributor to the rise is vitamin D. In this systematic review, we examined the literature around vitamin D and T1D. We identified 22 papers examining the role of vitamin D in cultured β-cell lines, islets, or perfused pancreas, and 28 papers examining vitamin D in humans or human islets. The literature reports strong associations between T1D and low circulating vitamin D. There is also high-level (systematic reviews, meta-analyses) evidence that adequate vitamin D status in early life reduces T1D risk. Several animal studies, particularly in NOD mice, show harm from D-deficiency and benefit in most studies from vitamin D treatment/supplementation. Short-term streptozotocin studies show a β-cell survival effect with supplementation. Human studies report associations between VDR polymorphisms and T1D risk and β-cell function, as assessed by C-peptide. In view of those outcomes, the variable results in human trials are generally disappointing. Most studies using 1,25D, the active form of vitamin D were ineffective. Similarly, studies using other forms of vitamin D were predominantly ineffective. However, it is interesting to note that all but one of the studies testing 25D reported benefit. Together, this suggests that maintenance of optimal circulating 25D levels may reduce the risk of T1D and that it may have potential for benefits in delaying the development of absolute or near-absolute C-peptide deficiency. Given the near-complete loss of β-cells by the time of clinical diagnosis, vitamin D is much less likely to be useful after disease-onset. However, given the very low toxicity of 25D, and the known benefits of preservation of C-peptide positivity for long-term complications risk, we recommend considering daily cholecalciferol supplementation in people with T1D and people at high risk of T1D, especially if they have vitamin D insufficiency.
Topics: Mice; Animals; Humans; Vitamin D; Diabetes Mellitus, Type 1; C-Peptide; Mice, Inbred NOD; Vitamins
PubMed: 36430915
DOI: 10.3390/ijms232214434 -
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 -
The American Journal of Clinical... Oct 2019Low-glycemic index (GI) diets are thought to reduce postprandial glycemia, resulting in more stable blood glucose concentrations. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Low-glycemic index (GI) diets are thought to reduce postprandial glycemia, resulting in more stable blood glucose concentrations.
OBJECTIVE
We hypothesized that low-GI diets would be superior to other diet types in lowering measures of blood glucose control in people with type 1 or type 2 diabetes, or impaired glucose tolerance.
METHODS
We searched PubMed, the Cochrane Library, EMBASE, and clinical trials registries for published and unpublished studies up until 1 March, 2019. We included 54 randomized controlled trials in adults or children with impaired glucose tolerance, type 1 diabetes, or type 2 diabetes. Continuous data were synthesized using a random effects, inverse variance model, and presented as standardized mean differences with 95% CIs.
RESULTS
Low-GI diets were effective at reducing glycated hemoglobin (HbA1c), fasting glucose, BMI, total cholesterol, and LDL, but had no effect on fasting insulin, HOMA-IR, HDL, triglycerides, or insulin requirements. The reduction in fasting glucose and HbA1c was inversely correlated with body weight. The greatest reduction in fasting blood glucose was seen in the studies of the longest duration.
CONCLUSIONS
Low-GI diets may be useful for glycemic control and may reduce body weight in people with prediabetes or diabetes.
Topics: Blood Glucose; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diet; Glycemic Index; Humans; Insulin
PubMed: 31374573
DOI: 10.1093/ajcn/nqz149 -
Current Pain and Headache Reports Aug 2022Painful diabetic neuropathy (PDN) manifests with pain typically in the distal lower extremities and can be challenging to treat. The authors appraised the literature for... (Review)
Review
PURPOSE OF REVIEW
Painful diabetic neuropathy (PDN) manifests with pain typically in the distal lower extremities and can be challenging to treat. The authors appraised the literature for evidence on conservative, pharmacological, and neuromodulation treatment options for PDN.
RECENT FINDINGS
Intensive glycemic control with insulin in patients with type 1 diabetes may be associated with lower odds of distal symmetric polyneuropathy compared to patients who receive conventional insulin therapy. First-line pharmacologic therapy for PDN includes gabapentinoids (pregabalin and gabapentin) and duloxetine. Additional pharmacologic modalities that are approved by the Food and Drug Administration (FDA) but are considered second-line agents include tapentadol and 8% capsaicin patch, although studies have revealed modest treatment effects from these modalities. There is level I evidence on the use of dorsal column spinal cord stimulation (SCS) for treatment of PDN, delivering either a 10-kHz waveform or tonic waveform. In summary, this review provides an overview of treatment options for PDN. Furthermore, it provides updates on the level of evidence for SCS therapy in cases of PDN refractory to conventional medical therapy.
Topics: Diabetes Mellitus; Diabetic Neuropathies; Gabapentin; Humans; Insulins; Pregabalin; Spinal Cord Stimulation
PubMed: 35716275
DOI: 10.1007/s11916-022-01061-7 -
Clinical Toxicology (Philadelphia, Pa.) Oct 2020Beta-adrenoreceptor antagonist (beta-blocker) poisoning is a common overdose which can lead to significant morbidity and mortality. To evaluate the effects of...
Beta-adrenoreceptor antagonist (beta-blocker) poisoning is a common overdose which can lead to significant morbidity and mortality. To evaluate the effects of treatments for beta-adrenoreceptor antagonist poisoning. Searches were conducted across MEDLINE (1946-26 November 2019, Ovid); Embase (1974-26 November 2019, Ovid); and the Cochrane Central Register of Controlled Trials (CENTRAL, to 26 November 2019) utilising a combination of subject headings and free text. The search strategy identified 15, 553 citations. Two reviewers screened titles and abstracts prior to selecting 141 articles (Kappa on articles included = 0.982, 95% CI 0.980-0.985). Primary outcomes included mortality and improvement in haemodynamic parameters (e.g., heart rate, blood pressure or a composite measure able to quantitate a haemodynamic response). The risk of bias was high for all interventions. Fifteen case reports described the administration of activated charcoal and five detailed the use of gastric lavage. As there was concurrent utilisation of multiple interventions, it was difficult to draw definitive conclusions regarding the relative contribution of these interventions to mortality or survival. The use of catecholamines in treating beta-blocker toxicity was reported in 16 case reports, 3 case series and 2 animal studies. These agents most likely provided a survival benefit and improved haemodynamics. Multiple intravenous boluses of atropine were associated with improvement in heart rate and blood pressure in one case report. Intravenous calcium was associated with an improvement in haemodynamics in three out of six case reports but in association with multiple other therapies as well as in two animal studies. The use of this therapy was associated with mortality benefit in 10 case series. Two case reports showed clear haemodynamic improvement in a timeframe consistent with insulin administration (bolus then continuous infusion). Maintenance dosing ranged from 1 to 10 units/kg/h of insulin. However, it is unclear whether high-dose insulin euglycaemic therapy improved haemodynamic response above catecholamines and other inotropic agents in humans. Hypoglycaemia and hypokalemia were commonly observed adverse effects. Glucagon was associated with minor improvements in haemodynamics through an increase in heart rate in two cases series, nine case reports and five animal studies. Four case reports reported an association with improvement in haemodynamics following administration of methylene blue but in the setting of co-ingestion with amlodipine. There was variable response to intravenous lipid emulsion therapy reported in 10 case series, 5 animal studies and 21 case reports. There were four case reports showing variable response to lignocaine in arrhythmias secondary to beta-blocker toxicity. Fructose diphosphate, levosimendan and amrinone did not provide a mortality or significant haemodynamic benefit in three animal studies and nine case reports. . Veno-arterial extracorporeal membrane oxygenation was associated with improved survival in patients with severe cardiogenic shock or cardiac arrest in an observational study and four cases series. The evidence of four case reports suggest haemodialysis may assist in the management of massive overdose of specific water-soluble beta-blockers (e.g., atenolol) by improving elimination; however, a survival or haemodynamic benefit was not established. One case series and a single case report showed the utility of temporary overdrive cardiac pacing to prevent arrhythmias in sotalol toxicity. Catecholamines, vasopressors, high-dose insulin euglycaemic therapy and veno-arterial extracorporeal membrane oxygenation were associated with reduced mortality. However, it must be acknowledged that multiple treatments were often given simultaneously. Haemodynamic improvements in blood pressure and cardiac output were seen with the use of catecholamines, vasopressin and high-dose insulin euglycaemic therapy. Evidence for treatment recommendations is almost entirely drawn from very low- to low-quality studies and subject to bias. However, it is reasonable to have a graduated response to cardiovascular instability beginning with intravenous fluids, commencement of a single or a combination of catecholamine inotropes and vasopressors depending upon the type of haemodynamic compromise (bradycardia, left ventricular dysfunction, vasodilation). High-dose insulin euglycaemic therapy can be introduced as an adjunctive inotrope and lastly, more invasive methods such as veno-arterial extracorporeal membrane oxygenation should be considered in cases unresponsive to other therapies.
Topics: Adrenergic beta-Antagonists; Animals; Atropine; Catecholamines; Drug Overdose; Extracorporeal Membrane Oxygenation; Fat Emulsions, Intravenous; Hemodynamics; Humans; Insulin; Practice Guidelines as Topic
PubMed: 32310006
DOI: 10.1080/15563650.2020.1752918 -
Diabetes & Metabolic Syndrome Sep 2022Insulin icodec is currently the most advanced candidate insulin suitable for once-weekly administration. We aim to conduct a systematic review of the literature to find... (Review)
Review
BACKGROUND AND AIMS
Insulin icodec is currently the most advanced candidate insulin suitable for once-weekly administration. We aim to conduct a systematic review of the literature to find out the efficacy and safety of insulin icodec in patients with diabetes mellitus.
METHODS
We systematically searched the electronic database of PubMed, and Google Scholar from inception until August 20, 2022, using MeSH keywords. Ongoing trials of insulin icodec were additionally searched from the ClinicalTrials.Gov. We retrieved all the available granular details of phase 1 to phase 3 studies of insulin icodec in both type 1 and type 2 diabetes.
RESULTS
Phase 1 study showed insulin icodec having a half-life of 196 h (>1 week) while a steady state is achieved after 3 to 4 weekly injections. Phase 2 studies compared once-weekly icodec to insulin glargine (U-100) and found a similar glucose control with no significantly greater hypoglycemia risks. Top-line results from the five phase 3 studies reported better glucose control with once-weekly icodec compared to both once-daily insulin glargine (ONWARDS 1) and once-daily degludec (in both ONWARDS 2 and 4) with similar rates of hypoglycemia in type 2 diabetes, although there was a higher hypoglycemic event with insulin icodec in type 1 diabetes (ONWARDS 6) compared to once-daily degludec despite a similar glycemic control.
CONCLUSION
A brighter prospect of once-weekly insulin icodec is on the card in particular in type 2 diabetes in terms of reducing injection pricks by >85% vs. once-daily basal insulin analogs, although few unknowns still exist.
Topics: Humans; Insulin Glargine; Diabetes Mellitus, Type 2; Blood Glucose; Hypoglycemic Agents; Hypoglycemia; Glycated Hemoglobin
PubMed: 36108418
DOI: 10.1016/j.dsx.2022.102615 -
Archivos de La Sociedad Espanola de... Apr 2023The Purpose is to identify, through a systematic literature review, the current evidence regarding the effectiveness of topical insulin treatment in ocular surface... (Review)
Review
The Purpose is to identify, through a systematic literature review, the current evidence regarding the effectiveness of topical insulin treatment in ocular surface pathologies. A literature search was implemented in Medline (Pubmed), Embase and Web Of Science medical indexing databases by using keywords such as "insulin" AND "cornea" OR "corneal" OR "dry eye" in published papers in English or Spanish within the last eleven years (2011-2022). Nine papers were identified with 180 participants from the United States, Spain, Ireland, Canada, Portugal and Malaysia, with persistent refractory epithelial defects and secondary to vitrectomy, whose extension of the lesion was from 3,75mm to 65.47mm. The preparation was dissolved with artificial tears and the insulin concentration ranged from 1 IU/ml to 100 IU/ml. In all cases, the resolution of the clinical picture was complete with a healing time from 2.5 days to 60.9 days, the latter being a secondary case to a difficult-to-control caustic burn. Topical insulin has been effective for the treatment of persistent epithelial defects. The intermediate action and low concentrations showed a shorter resolution time in neurotrophic ulcers and induced during vitreoretinal surgery.
Topics: Humans; Insulin; Cornea; Wound Healing; Lubricant Eye Drops; Administration, Topical
PubMed: 36871851
DOI: 10.1016/j.oftale.2023.03.007