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The Journal of Clinical Endocrinology... Dec 2022The preventive effect of sodium-glucose cotransporter 2 (SGLT2) inhibitors for new-onset diabetes was investigated in secondary analyses of several randomized controlled... (Meta-Analysis)
Meta-Analysis
CONTEXT
The preventive effect of sodium-glucose cotransporter 2 (SGLT2) inhibitors for new-onset diabetes was investigated in secondary analyses of several randomized controlled trials (RCTs). However, the results were inconsistent.
OBJECTIVE
This work aimed to synthesize available evidence and evaluate whether SGLT2 inhibitors are effective in preventing new-onset diabetes.
METHODS
In this systematic review and meta-analysis of RCTs, MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials were searched through February 11, 2022. Two independent authors screened the search results and extracted summary data from eligible RCTs (including original and post hoc analyses) comparing SGLT2 inhibitors and placebo for the risk of new-onset diabetes among adults with prediabetes. Meta-analysis was conducted using random-effects models to calculate risk ratios and 95% CIs.
RESULTS
We included 4 RCTs with 5655 participants who had prediabetes. Based on the random-effects meta-analysis, SGLT2 inhibitors were significantly associated with a lower risk of new-onset diabetes (relative risk, 0.79; 95% CI, 0.68-0.93). The relative risks of new-onset diabetes in dapagliflozin and empagliflozin were 0.68 (95% CI, 0.52-0.89) and 0.87 (95% CI, 0.72-1.04), respectively (P-for-heterogeneity = .14). The frequency of severe hypoglycemia was not elevated in the SGLT2 inhibitors group compared to the placebo group.
CONCLUSION
In this meta-analysis, SGLT2 inhibitors were associated with a reduced risk of new-onset type 2 diabetes among adults with prediabetes and heart failure or chronic kidney disease. These findings indicate the potential usefulness of SGLT2 inhibitors in preventing diabetes among high-risk populations with prediabetes.
Topics: Adult; Humans; Sodium-Glucose Transporter 2 Inhibitors; Hypoglycemic Agents; Prediabetic State; Randomized Controlled Trials as Topic; Diabetes Mellitus, Type 2; Glucose; Sodium
PubMed: 36217306
DOI: 10.1210/clinem/dgac591 -
The American Journal of Psychiatry Apr 2015Public health campaigns encouraging early help seeking have increased rates of mild cognitive impairment (MCI) diagnosis in Western countries, but we know little about... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Public health campaigns encouraging early help seeking have increased rates of mild cognitive impairment (MCI) diagnosis in Western countries, but we know little about how to treat or predict dementia outcomes in persons with the condition.
METHOD
The authors searched electronic databases and references for longitudinal studies reporting potentially modifiable risk factors for incident dementia after MCI. Two authors independently evaluated study quality using a checklist. Meta-analyses were conducted of three or more studies.
RESULTS
There were 76 eligible articles. Diabetes and prediabetes increased risk of conversion from amnestic MCI to Alzheimer's dementia; risk in treated versus untreated diabetes was lower in one study. Diabetes was also associated with increased risk of conversion from any-type or nonamnestic MCI to all-cause dementia. Metabolic syndrome and prediabetes predicted all-cause dementia in people with amnestic and any-type MCI, respectively. Mediterranean diet decreased the risk of conversion to Alzheimer's dementia. The presence of neuropsychiatric symptoms or lower serum folate levels predicted conversion from any-type MCI to all-cause dementia, but less formal education did not. Depressive symptoms predicted conversion from any-type MCI to all-cause dementia in epidemiological but not clinical studies.
CONCLUSIONS
Diabetes increased the risk of conversion to dementia. Other prognostic factors that are potentially manageable are prediabetes and the metabolic syndrome, neuropsychiatric symptoms, and low dietary folate. Dietary interventions and interventions to reduce neuropsychiatric symptoms, including depression, that increase risk of conversion to dementia may decrease new incidence of dementia.
Topics: Alzheimer Disease; Cognitive Dysfunction; Dementia; Depression; Diabetes Mellitus; Diet, Mediterranean; Disease Progression; Educational Status; Folic Acid; Humans; Longitudinal Studies; Metabolic Syndrome; Prediabetic State; Protective Factors; Risk Factors
PubMed: 25698435
DOI: 10.1176/appi.ajp.2014.14070878 -
BMJ Open Nov 2017Explore the cost-effectiveness of lifestyle interventions and metformin in reducing subsequent incidence of type 2 diabetes, both alone and in combination with a... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Explore the cost-effectiveness of lifestyle interventions and metformin in reducing subsequent incidence of type 2 diabetes, both alone and in combination with a screening programme to identify high-risk individuals.
DESIGN
Systematic review of economic evaluations.
DATA SOURCES AND ELIGIBILITY CRITERIA
Database searches (Embase, Medline, PreMedline, NHS EED) and citation tracking identified economic evaluations of lifestyle interventions or metformin alone or in combination with screening programmes in people at high risk of developing diabetes. The International Society for Pharmaco-economics and Outcomes Research's Questionnaire to Assess Relevance and Credibility of Modelling Studies for Informing Healthcare Decision Making was used to assess study quality.
RESULTS
27 studies were included; all had evaluated lifestyle interventions and 12 also evaluated metformin. Primary studies exhibited considerable heterogeneity in definitions of pre-diabetes and intensity and duration of lifestyle programmes. Lifestyle programmes and metformin appeared to be cost effective in preventing diabetes in high-risk individuals (median incremental cost-effectiveness ratios of £7490/quality-adjusted life-year (QALY) and £8428/QALY, respectively) but economic estimates varied widely between studies. Intervention-only programmes were in general more cost effective than programmes that also included a screening component. The longer the period evaluated, the more cost-effective interventions appeared. In the few studies that evaluated other economic considerations, budget impact of prevention programmes was moderate (0.13%-0.2% of total healthcare budget), financial payoffs were delayed (by 9-14 years) and impact on incident cases of diabetes was limited (0.1%-1.6% reduction). There was insufficient evidence to answer the question of (1) whether lifestyle programmes are more cost effective than metformin or (2) whether low-intensity lifestyle interventions are more cost effective than the more intensive lifestyle programmes that were tested in trials.
CONCLUSIONS
The economics of preventing diabetes are complex. There is some evidence that diabetes prevention programmes are cost effective, but the evidence base to date provides few clear answers regarding design of prevention programmes because of differences in denominator populations, definitions, interventions and modelling assumptions.
Topics: Cost-Benefit Analysis; Diabetes Mellitus, Type 2; Humans; Life Style; Metformin; Prediabetic State; Preventive Health Services; Quality-Adjusted Life Years; Randomized Controlled Trials as Topic
PubMed: 29146638
DOI: 10.1136/bmjopen-2017-017184 -
Diabetes Care Jul 2020While observational studies have shown an association between vitamin D insufficiency and diabetes, it is unclear whether intervention with vitamin D supplements can... (Meta-Analysis)
Meta-Analysis
BACKGROUND
While observational studies have shown an association between vitamin D insufficiency and diabetes, it is unclear whether intervention with vitamin D supplements can lower the risk of type 2 diabetes mellitus (T2DM).
PURPOSE
To assess whether vitamin D supplementation reduces the risk of T2DM in people with prediabetes.
DATA SOURCES
We searched MEDLINE, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) from inception to 5 July 2019.
STUDY SELECTION
We included randomized controlled trials assessing vitamin D supplementation versus placebo in relation to new-onset T2DM in people with prediabetes.
DATA EXTRACTION
We screened studies and extracted data from published trials independently.
DATA SYNTHESIS
We identified eight eligible trials with a total of 4,896 subjects. Vitamin D supplementation significantly reduced the risk of T2DM (risk ratio [RR] 0.89 [95% CI 0.80-0.99]; = 0%). Benefit was found in nonobese subjects (RR 0.73 [95% CI 0.57-0.92]) but not in obese subjects (RR 0.95 [95% CI 0.84-1.08]) ( = 0.048). The reversion of prediabetes to normoglycemia occurred in 116 of 548 (21.2%) participants in the vitamin D group and 75 of 532 (14.1%) in the control group. Vitamin D supplementation increased reversion rate of prediabetes to normoglycemia (RR 1.48 [95% CI 1.14-1.92]; = 0%.) LIMITATIONS: Definitions of prediabetes and new-onset diabetes in eligible studies were different, and long-term data on outcomes of T2DM prevention were lacking.
CONCLUSIONS
In persons with prediabetes, vitamin D supplementation reduces the risk of T2DM and increases the reversion rate of prediabetes to normoglycemia. The benefit of the prevention of T2DM could be limited to nonobese subjects. Individual participant data meta-analyses are needed to confirm these findings.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Controlled Clinical Trials as Topic; Diabetes Mellitus, Type 2; Dietary Supplements; Female; Humans; Male; Middle Aged; Prediabetic State; Vitamin D; Young Adult
PubMed: 33534730
DOI: 10.2337/dc19-1708 -
Diabetes, Obesity & Metabolism Aug 2019Traditional Chinese medicine (TCM) has recorded knowledge of diabetes for over 2000 years. Because a considerable number of TCM studies exhibit design defects, such as... (Meta-Analysis)
Meta-Analysis
Traditional Chinese medicine (TCM) has recorded knowledge of diabetes for over 2000 years. Because a considerable number of TCM studies exhibit design defects, such as limited intervention duration, small sample sizes and inconsistent efficacy evaluations, the role of TCM in the treatment of diabetes cannot be fully elucidated. In this review, we evaluate randomized controlled trials of prediabetes, diabetes and diabetic complications published in the past decade. We found that TCM could significantly improve glucose control and clinical indices in patients with diabetes and effectively delay the progression of diabetes. We also summarize potential pharmacological mechanisms underlying the efficacy of TCM medication/herbs and their active ingredients for treating diabetes. More rigorously designed experiments and long-term evaluation of TCM for diabetes will allow for more effective diabetes management.
Topics: Adult; Diabetes Complications; Diabetes Mellitus, Type 2; Drugs, Chinese Herbal; Female; Humans; Male; Medicine, Chinese Traditional; Phytotherapy; Prediabetic State; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 31050124
DOI: 10.1111/dom.13760 -
Diabetes, Obesity & Metabolism Dec 2022Very low carbohydrate/ketogenic diets (VLC/KDs) are popular but their role in managing pre-diabetes and type 2 diabetes (T2D) is uncertain. This study uses a systematic... (Meta-Analysis)
Meta-Analysis
AIM
Very low carbohydrate/ketogenic diets (VLC/KDs) are popular but their role in managing pre-diabetes and type 2 diabetes (T2D) is uncertain. This study uses a systematic review and meta-analysis of randomized controlled trials to estimate the effect of these diets in this population.
MATERIALS AND METHODS
A systematic review identified randomized controlled trials of at least 6 months duration comparing efficacy and safety of VLC/KDs (≤50 g carbohydrate or ≤10% total energy from carbohydrate per day) with a control diet (carbohydrate above the VLC/KD threshold) in adults with pre-diabetes or T2D. The primary outcome variable was glycated haemoglobin (HbA1c) after 12 months. The meta-analysis method was inverse variance weighting of mean values for continuous variables.
RESULTS
Key word searches identified 2290 studies; 2221 were not in scope. A full text review of 69 studies identified eight meeting inclusion criteria; in total, it involved 606 participants. Six studies reported HbA1c (%) at 12 months; four as change from baseline with a fixed effects estimate (95% confidence interval): VLC/KD minus control of 0.01% (-0.22 to 0.25), p = .91; and two as change from baseline: -0.65% (-0.99; -0.31) [-7.1 mmol/mol (-10.8; -3.4)], p < .001. Serum triglycerides were lower with VLC/KD versus control: -0.28 mmol/L (-0.44 to -0.11), p < .001. High-density lipoprotein was higher with an estimate of 0.04 mmol/L (0.01 to 0.08), p = .03, in the five studies reporting 12-month summary data.
CONCLUSIONS
A VLC/KD may cause reductions in HbA1c and triglycerides in those with pre-diabetes or T2D but evidence of an advantage over other strategies is limited. More well-designed studies are required to provide certain evidence.
Topics: Adult; Humans; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Diet, Ketogenic; Prediabetic State; Randomized Controlled Trials as Topic; Diet, Carbohydrate-Restricted; Triglycerides
PubMed: 36064937
DOI: 10.1111/dom.14837 -
Diabetes Research and Clinical Practice Oct 2019Cinnamon has been used as a dietary component and in the management of diabetes mellitus. This study systematically reviewed and synthesized evidence on the efficacy of... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Cinnamon has been used as a dietary component and in the management of diabetes mellitus. This study systematically reviewed and synthesized evidence on the efficacy of cinnamon for the treatment of type 2 diabetes mellitus (T2DM) and pre-diabetes patients.
METHODS
Databases of Web of Sciences, the Cochrane library, PubMed, CINAHL and SCOPUS were searched. Stata version 13 (College Station, Texas 77845 USA) and RevMan var. 5.3 software were used for meta-analysis. Heterogeneity was assessed using Chi-square and I tests.
RESULTS
Sixteen randomized controlled studies were included in the meta-analysis. Cinnamon significantly reduced fasting blood glucose (FBG) and homeostatic model assessment for insulin resistance (HOMA-IR) level compared to placebo with weighted mean difference (WMD) of -0.545 (95% CI: -0.910, -0.18) mmol/L, I = 83.6% and -0.714(-1.388, -0.04), I = 84.4% respectively. There was no significant change in weighted mean difference of glycosylated hemoglobin A1C (HbA1c) % and lipid profiles (mmol/L). Meta-regression did not show any factor significantly affecting the treatment response.
CONCLUSION
Cinnamon reduced FBG and HOMA-IR, level in T2DM and pre-diabetes patients compared to placebo. High heterogeneity observed among included studies warrants further clinical trials after standardization of cinnamon formulation.
Topics: Cinnamomum zeylanicum; Diabetes Mellitus, Type 2; Humans; Prediabetic State
PubMed: 31425768
DOI: 10.1016/j.diabres.2019.107815 -
Minerva Endocrinology Sep 2022Certain pharmacological and lifestyle interventions have been shown to reduce progression of prediabetes. We aimed to perform a systematic review and meta-analyses of... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Certain pharmacological and lifestyle interventions have been shown to reduce progression of prediabetes. We aimed to perform a systematic review and meta-analyses of studies assessing the outcomes of zinc supplementation in individuals with prediabetes.
EVIDENCE ACQUISITION
A comprehensive search was conducted in PubMed, SciVerse Scopus and Web of Science databases. Controlled clinical trials in prediabetics individuals, on zinc supplementation with or without other nutrients, assessing at least one accepted glycemic parameter as an outcome were deemed eligible.
EVIDENCE SYNTHESIS
Three papers were included in the systematic review and meta-analysis, with a total of 265 participants. Duration of zinc supplementation ranged from 6-12 months. The zinc dose ranged from 20-30 mg/day. In the pooled analysis, zinc supplementation significantly reduced FBG both when given alone (-10.86 mg/dL; 95% CI, -14.74 to -6.98; P<0.001) and with other micronutrients (-11.77 mg/dL; P<0.001). Similarly, 2hr-OGTT blood glucose was reduced by 21.08 mg/dL (95% CI, -40.05 to -2.11; P=0.03) in the pooled analysis of studies using zinc alone and in combination with other micronutrients. One study demonstrated a significant reduction of HbA
1c by 0.5% with combined supplementation, while another reported a significant reduction in CRP with zinc supplementation. When all trials were considered, TC, HDL-c and HOMA-β showed significant improvement. Zinc supplementation significantly improved the zinc status from baseline.CONCLUSIONS
Zinc supplementation demonstrated beneficial effects on glycemic and lipid parameters in individuals with prediabetes. It may have the potential to reduce the prevalence of prediabetes and control associated morbidity and mortality.
Topics: Blood Glucose; Dietary Supplements; Humans; Lipids; Micronutrients; Prediabetic State; Zinc
PubMed: 33759442
DOI: 10.23736/S2724-6507.21.03234-X -
The Cochrane Database of Systematic... Oct 2018Intermediate hyperglycaemia (IH) is characterised by one or more measurements of elevated blood glucose concentrations, such as impaired fasting glucose (IFG), impaired... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Intermediate hyperglycaemia (IH) is characterised by one or more measurements of elevated blood glucose concentrations, such as impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and elevated glycosylated haemoglobin A1c (HbA1c). These levels are higher than normal but below the diagnostic threshold for type 2 diabetes mellitus (T2DM). The reduced threshold of 5.6 mmol/L (100 mg/dL) fasting plasma glucose (FPG) for defining IFG, introduced by the American Diabetes Association (ADA) in 2003, substantially increased the prevalence of IFG. Likewise, the lowering of the HbA1c threshold from 6.0% to 5.7% by the ADA in 2010 could potentially have significant medical, public health and socioeconomic impacts.
OBJECTIVES
To assess the overall prognosis of people with IH for developing T2DM, regression from IH to normoglycaemia and the difference in T2DM incidence in people with IH versus people with normoglycaemia.
SEARCH METHODS
We searched MEDLINE, Embase, ClincialTrials.gov and the International Clinical Trials Registry Platform (ICTRP) Search Portal up to December 2016 and updated the MEDLINE search in February 2018. We used several complementary search methods in addition to a Boolean search based on analytical text mining.
SELECTION CRITERIA
We included prospective cohort studies investigating the development of T2DM in people with IH. We used standard definitions of IH as described by the ADA or World Health Organization (WHO). We excluded intervention trials and studies on cohorts with additional comorbidities at baseline, studies with missing data on the transition from IH to T2DM, and studies where T2DM incidence was evaluated by documents or self-report only.
DATA COLLECTION AND ANALYSIS
One review author extracted study characteristics, and a second author checked the extracted data. We used a tailored version of the Quality In Prognosis Studies (QUIPS) tool for assessing risk of bias. We pooled incidence and incidence rate ratios (IRR) using a random-effects model to account for between-study heterogeneity. To meta-analyse incidence data, we used a method for pooling proportions. For hazard ratios (HR) and odds ratios (OR) of IH versus normoglycaemia, reported with 95% confidence intervals (CI), we obtained standard errors from these CIs and performed random-effects meta-analyses using the generic inverse-variance method. We used multivariable HRs and the model with the greatest number of covariates. We evaluated the certainty of the evidence with an adapted version of the GRADE framework.
MAIN RESULTS
We included 103 prospective cohort studies. The studies mainly defined IH by IFG (FPG mmol/L 5.6 to 6.9 mmol/L or 100 mg/dL to 125 mg/dL), IFG (FPG 6.1 mmol/L to 6.9 mmol/L or 110 mg/dL to 125 mg/dL), IGT (plasma glucose 7.8 mmol/L to 11.1 mmol/L or 140 mg/dL to 199 mg/dL two hours after a 75 g glucose load on the oral glucose tolerance test, combined IFG and IGT (IFG/IGT), and elevated HbA1c (HbA1c: HbA1c 5.7% to 6.4% or 39 mmol/mol to 46 mmol/mol; HbA1c: HbA1c 6.0% to 6.4% or 42 mmol/mol to 46 mmol/mol). The follow-up period ranged from 1 to 24 years. Ninety-three studies evaluated the overall prognosis of people with IH measured by cumulative T2DM incidence, and 52 studies evaluated glycaemic status as a prognostic factor for T2DM by comparing a cohort with IH to a cohort with normoglycaemia. Participants were of Australian, European or North American origin in 41 studies; Latin American in 7; Asian or Middle Eastern in 50; and Islanders or American Indians in 5. Six studies included children and/or adolescents.Cumulative incidence of T2DM associated with IFG, IFG, IGT and the combination of IFG/IGT increased with length of follow-up. Cumulative incidence was highest with IFG/IGT, followed by IGT, IFG and IFG. Limited data showed a higher T2DM incidence associated with HbA1c compared to HbA1c. We rated the evidence for overall prognosis as of moderate certainty because of imprecision (wide CIs in most studies). In the 47 studies reporting restitution of normoglycaemia, regression ranged from 33% to 59% within one to five years follow-up, and from 17% to 42% for 6 to 11 years of follow-up (moderate-certainty evidence).Studies evaluating the prognostic effect of IH versus normoglycaemia reported different effect measures (HRs, IRRs and ORs). Overall, the effect measures all indicated an elevated risk of T2DM at 1 to 24 years of follow-up. Taking into account the long-term follow-up of cohort studies, estimation of HRs for time-dependent events like T2DM incidence appeared most reliable. The pooled HR and the number of studies and participants for different IH definitions as compared to normoglycaemia were: IFG: HR 4.32 (95% CI 2.61 to 7.12), 8 studies, 9017 participants; IFG: HR 5.47 (95% CI 3.50 to 8.54), 9 studies, 2818 participants; IGT: HR 3.61 (95% CI 2.31 to 5.64), 5 studies, 4010 participants; IFG and IGT: HR 6.90 (95% CI 4.15 to 11.45), 5 studies, 1038 participants; HbA1c: HR 5.55 (95% CI 2.77 to 11.12), 4 studies, 5223 participants; HbA1c: HR 10.10 (95% CI 3.59 to 28.43), 6 studies, 4532 participants. In subgroup analyses, there was no clear pattern of differences between geographic regions. We downgraded the evidence for the prognostic effect of IH versus normoglycaemia to low-certainty evidence due to study limitations because many studies did not adequately adjust for confounders. Imprecision and inconsistency required further downgrading due to wide 95% CIs and wide 95% prediction intervals (sometimes ranging from negative to positive prognostic factor to outcome associations), respectively.This evidence is up to date as of 26 February 2018.
AUTHORS' CONCLUSIONS
Overall prognosis of people with IH worsened over time. T2DM cumulative incidence generally increased over the course of follow-up but varied with IH definition. Regression from IH to normoglycaemia decreased over time but was observed even after 11 years of follow-up. The risk of developing T2DM when comparing IH with normoglycaemia at baseline varied by IH definition. Taking into consideration the uncertainty of the available evidence, as well as the fluctuating stages of normoglycaemia, IH and T2DM, which may transition from one stage to another in both directions even after years of follow-up, practitioners should be careful about the potential implications of any active intervention for people 'diagnosed' with IH.
Topics: Blood Glucose; Diabetes Mellitus, Type 2; Disease Progression; Humans; Hyperglycemia; Incidence; Prediabetic State; Prognosis; Prospective Studies
PubMed: 30371961
DOI: 10.1002/14651858.CD012661.pub2