Fasting Glucose Variation Predicts Microvascular Risk in ACCORD and VADT

Abstract Aims The association of glycemic variability with microvascular disease complications in type 2 diabetes (T2D) has been understudied and remains unclear. We investigated this relationship using both Action to Control Cardiovascular Risk in Diabetes (ACCORD) and the Veteran Affairs Diabetes Trial (VADT). Methods In ACCORD, fasting plasma glucose (FPG) was measured 1-3 times/year for up to 84 months in 10,251 individuals. In the VADT, FPG was measured every 3 months for up to 87 months in 1,791 individuals. Variability measures included coefficient of variation (CV) and average real variability (ARV) for fasting glucose. The primary composite outcome was time to either severe nephropathy or retinopathy event and secondary outcomes included each outcome individually. To assess the association, we considered variability measures as time-dependent covariates in Cox proportional hazard models. We conducted a meta-analysis across the two trials to estimate the risk of fasting glucose variability as well as to assess the heterogenous effects of FPG variability across treatment arms. Results In both ACCORD and the VADT, CV and ARV of FPG were associated with development of future microvascular outcomes even after adjusting for other risk factors, including measures of average glycemic control (i.e., cumulative average of HbA1c). Meta-analyses of these two trials confirmed these findings and indicated FPG variation may be more harmful in those with less intensive glucose control. Conclusions This post-hoc analysis indicates that variability of FPG plays a role in, and/or is an independent and readily available marker of, development of microvascular complications in T2D.

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Effect of folate supplementation on insulin sensitivity and type 2 diabetes: a meta-analysis of randomized controlled trials

American Journal of Clinical Nutrition ◽

10.1093/ajcn/nqy234 ◽

2019 ◽

Vol 109 (1) ◽

pp. 29-42 ◽

Cited By ~ 13

Author(s):

Mads Vendelbo Lind ◽

Lotte Lauritzen ◽

Mette Kristensen ◽

Alastair B Ross ◽

Jane Nygaard Eriksen

Keyword(s):

Insulin Resistance ◽

Type 2 Diabetes ◽

Randomized Controlled Trials ◽

Fasting Glucose ◽

Meta Analysis ◽

Controlled Trials ◽

Folate Supplementation ◽

Randomized Controlled ◽

Meta Analyses

ABSTRACT Background Various mechanisms link higher total homocysteine to higher insulin resistance (IR) and risk of type 2 diabetes (T2D). Folate supplementation is recognized as a way to lower homocysteine. However, randomized controlled trials (RCTs) show inconsistent results on IR and T2D outcomes. Objective The aim of this study was to examine the effect of folate supplementation on IR and T2D outcomes. Design We conducted a systematic literature search in PubMed, Web of Science, and EMBASE and prior systematic reviews and meta-analyses and identified 29 RCTs (22,250 participants) that assessed the effect of placebo-controlled folate supplementation alone or in combination with other B vitamins on fasting glucose, insulin, homeostasis model assessment for insulin resistance (HOMA-IR), glycated hemoglobin (HbA1c), or risk of T2D. The meta-analysis was conducted using both random- and fixed-effects models to calculate weighted mean differences (WMDs) or risk ratios with 95% CIs. Subgroup analyses were conducted based on intervention type (folate alone or in combination with other B vitamins), as well as analysis based on population characteristics, duration, dose, and change in homocysteine. Results When compared with placebo, folate supplementation lowered fasting insulin (WMD: −13.47 pmol/L; 95% CI: −21.41, −5.53 pmol/L; P < 0.001) and HOMA-IR (WMD: −0.57 units; 95% CI: −0.76, −0.37 units; P < 0.0001), but no overall effects were observed for fasting glucose or HbA1c. Heterogeneity was low in all meta-analyses, and subgroup analysis showed no signs of effect modification except for change in homocysteine, with the most pronounced effects in trials with a change of >2.5 µmol/L. Changes in homocysteine after folate supplementation correlated with changes in fasting glucose (β = 0.07; 95% CI: 0.01, 0.14; P = 0.025) and HbA1c (β = 0.46; 95% CI: 0.06, 0.85; P = 0.02). Only 2 studies examined folate supplementation on risk of T2D, and they found no change in RR (pooled RR: 0.91; 95% CI: 0.80, 1.04; P = 0.16). Conclusion Folate supplementation might be beneficial for glucose homeostasis and lowering IR, but at present there are insufficient data to conclusively determine the effect on development of T2D. This trial was registered on the Prospero database as CRD42016048254.

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Visit-to-Visit Fasting Glucose Variability in Young Adulthood and Cardiac Structure and Function at Midlife: The CARDIA Study

Frontiers in Cardiovascular Medicine ◽

10.3389/fcvm.2021.687054 ◽

2021 ◽

Vol 8 ◽

Author(s):

Zhenyu Xiong ◽

Peihan Xie ◽

Jiaying Li ◽

Zhi-chong Chen ◽

Yifen Lin ◽

...

Keyword(s):

Young Adulthood ◽

Fasting Glucose ◽

Glycemic Variability ◽

Glucose Variability ◽

Left Ventricular ◽

Structure And Function ◽

Cardiac Structure ◽

Early Peak ◽

Cardiac Structure And Function ◽

And Function

Glycemic variability was found associated with left ventricular structure and function in type 2 diabetes. But it is still unclear that whether the greater visit-to-visit fasting glucose (FG) variability in young adulthood among the community population is associated with cardiac function alteration and cardiac remodeling at midlife. The community-based prospective cohort study of Coronary Artery Risk in Young Adult (CARDIA) recruited young participants at the baseline age of 18–30 years during the period of 1985–1986 (Year 0). FG was measured at Year 0, 2, 10, 15, 20, and 25. The echocardiographic evaluation of cardiac structure and function was conducted at year 25. A total of 2,600 young adults mean (SD) aged at 24.9 years (3.6) of which 57.3% were women and 46.7% were African Americans had been included in the study. After multivariable adjusted, higher SD of mean FG (SDFG) is associated with lower early peak diastolic septal mitral annular velocity (e') (β [SE], −0.214 [0.080], P < 0.01) and higher E/e' (β [SE], 0.307 [0.094], P < 0.01), and higher coefficient of variation of the mean FG (CVFG) is also associated with lower e' (β [SE], −0.141[0.066], P < 0.05) and higher E/e' (β [SE], 0.204 [0.078], P < 0.01). The higher average real variation of mean FG (ARVFG) is associated with higher E/e' (β [SE], 0.178 [0.085], P < 0.05) and higher left ventricular mass index (LVMI) (β [SE], 1.240 [0.618], P < 0.05). The higher FG variability in young adulthood is associated with the subclinical change of left ventricular (LV) diastolic function at midlife.

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Novel DNA methylation sites of glucose and insulin homeostasis: an integrative cross-omics analysis

10.1101/432070 ◽

2018 ◽

Author(s):

Jun Liu ◽

Elena Carnero-Montoro ◽

Jenny van Dongen ◽

Samantha Lent ◽

Ivana Nedeljkovic ◽

...

Keyword(s):

Dna Methylation ◽

Glucose Level ◽

In Silico ◽

Fasting Glucose ◽

Meta Analysis ◽

Tissue Expression ◽

P Value ◽

Cis Acting ◽

Functional Relevance ◽

Meta Analyses

Despite existing reports on differential DNA methylation in type 2 diabetes (T2D) and obesity, our understanding of the functional relevance of the phenomenon remains limited. Because obesity is the main risk factor for T2D and a driver of methylation from previous study, we aimed to explore the effect of DNA methylation in the early phases of T2D pathology while accounting for body mass index (BMI). We performed a blood-based epigenome-wide association study (EWAS) of fasting glucose and insulin among 4,808 non-diabetic European individuals and replicated the findings in an independent sample consisting of 11,750 non-diabetic subjects. We integrated blood-based in silico cross-omics databases comprising genomics, epigenomics and transcriptomics collected by BIOS project of the Biobanking and BioMolecular resources Research Infrastructure of the Netherlands (BBMRI-NL), the Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC), the DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) consortium, and the tissue-specific Genotype-Tissue Expression (GTEx) project. We identified and replicated nine novel differentially methylated sites in whole blood (P-value < 1.27 × 10-7): sites in LETM1, RBM20, IRS2, MAN2A2 genes and 1q25.3 region were associated with fasting insulin; sites in FCRL6, SLAMF1, APOBEC3H genes and 15q26.1 region were associated with fasting glucose. The association between SLAMF1, APOBEC3H and 15q26.1 methylation sites and glucose emerged only when accounted for BMI. Follow-up in silico cross-omics analyses indicate that the cis-acting meQTLs near SLAMF1 and SLAMF1 expression are involved in glucose level regulation. Moreover, our data suggest that differential methylation in FCRL6 may affect glucose level and the risk of T2D by regulating FCLR6 expression in the liver. In conclusion, the present study provided nine new DNA methylation sites associated with glycemia homeostasis and also provided new insights of glycemia related loci into the genetics, epigenetics and transcriptomics pathways based on the integration of cross-omics data in silico.

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Impact of age at type 2 diabetes mellitus diagnosis on mortality and vascular complications: systematic review and meta-analyses

Diabetologia ◽

10.1007/s00125-020-05319-w ◽

2020 ◽

Author(s):

Natalie Nanayakkara ◽

Andrea J. Curtis ◽

Stephane Heritier ◽

Adelle M. Gadowski ◽

Meda E. Pavkov ◽

...

Keyword(s):

Type 2 Diabetes ◽

Observational Studies ◽

Microvascular Complications ◽

Microvascular Disease ◽

Age At Diagnosis ◽

Diabetes Diagnosis ◽

Risk Of Mortality ◽

All Cause Mortality ◽

Meta Analyses

Abstract Aims/hypothesis Few studies examine the association between age at diagnosis and subsequent complications from type 2 diabetes. This paper aims to summarise the risk of mortality, macrovascular complications and microvascular complications associated with age at diagnosis of type 2 diabetes. Methods Data were sourced from MEDLINE and All EBM (Evidence Based Medicine) databases from inception to July 2018. Observational studies, investigating the effect of age at diabetes diagnosis on macrovascular and microvascular diabetes complications in adults with type 2 diabetes were selected according to pre-specified criteria. Two investigators independently extracted data and evaluated all studies. If data were not reported in a comparable format, data were obtained from authors, presented as minimally adjusted ORs (and 95% CIs) per 1 year increase in age at diabetes diagnosis, adjusted for current age for each outcome of interest. The study protocol was recorded with PROSPERO International Prospective Register of Systematic Reviews (CRD42016043593). Results Data from 26 observational studies comprising 1,325,493 individuals from 30 countries were included. Random-effects meta-analyses with inverse variance weighting were used to obtain the pooled ORs. Age at diabetes diagnosis was inversely associated with risk of all-cause mortality and macrovascular and microvascular disease (all p < 0.001). Each 1 year increase in age at diabetes diagnosis was associated with a 4%, 3% and 5% decreased risk of all-cause mortality, macrovascular disease and microvascular disease, respectively, adjusted for current age. The effects were consistent for the individual components of the composite outcomes (all p < 0.001). Conclusions/interpretation Younger, rather than older, age at diabetes diagnosis was associated with higher risk of mortality and vascular disease. Early and sustained interventions to delay type 2 diabetes onset and improve blood glucose levels and cardiovascular risk profiles of those already diagnosed are essential to reduce morbidity and mortality.

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Diagnosing type 2 diabetes using Hemoglobin A1c: a systematic review and meta-analysis of the diagnostic cutpoint based on microvascular complications

Acta Diabetologica ◽

10.1007/s00592-020-01606-5 ◽

2020 ◽

Author(s):

Alexandra E. Butler ◽

Emma English ◽

Eric S. Kilpatrick ◽

Linda Östlundh ◽

Hiam S. Chemaitelly ◽

...

Keyword(s):

Random Effects ◽

Hemoglobin A1c ◽

Meta Analysis ◽

Microvascular Complications ◽

Grey Literature ◽

High Specificity ◽

Diagnostic Threshold ◽

Published Evidence ◽

Meta Regression ◽

Meta Analyses

Abstract Aims Diabetic microvascular complications of retinopathy, nephropathy and neuropathy may occur at hemoglobin A1c levels (HbA1c) below the 6.5% (48 mmol/mol) diagnostic threshold. Our objective was to assess the validity of the HbA1c diagnostic cutpoint of 6.5% based upon published evidence of the prevalence of retinopathy, nephropathy and neuropathy as markers of diabetes. Methods Data Sources PubMed, Embase, Cochrane, Scopus and CINAHL from 1990-March 2019, grey literature sources. Study Selection All studies reported after 1990 (to ensure standardized HbA1c values) where HbA1c levels were presented in relation to prevalence of retinopathy, nephropathy or neuropathy in subjects not known to have diabetes. Data Extraction Studies were screened independently, data abstracted, and risk of bias appraised. Data Synthesis Data were synthesized using HbA1c categories of < 6.0% (< 42 mmol/mol), 6.0–6.4% (42–47 mmol/mol) and ≥ 6.5% (≥ 48 mmol/mol). Random-effects meta-analyses were conducted for retinopathy, nephropathy and neuropathy prevalence stratified by HbA1c categories. Random-effects multivariable meta-regression was conducted to identify predictors of retinopathy prevalence and sources of between-study heterogeneity. Results Pooled mean prevalence was: 4.0%(95% CI: 3.2–5.0%) for retinopathy, 10.5% (95% CI: 4.0–19.5%) for nephropathy, 2.5% (95% CI: 1.1–4.3%) for neuropathy. Mean prevalence when stratified for HbA1c < 6.0%, 6.0–6.4% and ≥ 6.5% was: retinopathy: 3.4% (95% CI: 1.8–5.4%), 2.3% (95% CI: 1.6–3.2%) and 7.8%(95% CI: 5.7–10.3%); nephropathy: 7.1% (95% CI: 1.7–15.9%), 9.6% (95% CI: 0.8–26.4%) and 17.1% (95% CI: 1.0–46.9%); neuropathy: 2.1% (95% CI: 0.0–6.8%), 3.4% (95% CI: 0.0–11.6%) and 2.8% (95% CI: 0.0–12.8%). Multivariable meta-regression showed HbA1c ≥ 6.5% (OR: 4.05; 95% CI: 1.92–8.57%), age > 55 (OR: 3.23; 95% CI 1.81–5.77), and African-American race (OR: 10.73; 95% CI: 4.34–26.55), to be associated with higher retinopathy prevalence. Marked heterogeneity in prevalence estimates was found across all meta-analyses (Cochran’s Q-statistic p < 0.0001). Conclusions The prevalence of nephropathy and moderate retinopathy was increased in subjects with HbA1c values ≥ 6.5% confirming the high specificity of this value for diagnosing T2DM; however, at HbA1c < 6.5% retinopathy increased at age > 55 years and, most strikingly, in African-Americans, suggesting there may be excess microvascular complication prevalence (particularly nephropathy) in individuals below the diabetes diagnostic threshold.

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Association Between Fasting Glucose Variability in Young Adulthood and the Progression of Coronary Artery Calcification in Middle Age

10.2337/figshare.12588878 ◽

2020 ◽

Author(s):

Weijing Feng ◽

Zhibin Li ◽

Wenjie Guo ◽

Xianglin Fan ◽

Feiran Zhou ◽

...

Keyword(s):

Coronary Artery ◽

Young Adulthood ◽

Coronary Artery Calcification ◽

Middle Age ◽

Fasting Glucose ◽

Glucose Variability ◽

Diabetes Incidence ◽

The Difference ◽

Average Real Variability

OBJECTIVE <a>To investigate whether intraindividual variability of fasting glucose (FG) in young adulthood is associated with coronary artery calcification (CAC) progression in middle age.</a> RESEARCH DESIGN AND METHODS We included 2,256 CARDIA (<a></a><a>Coronary Artery Risk Development Study in Young Adults</a>) participants with CAC assessment by computed tomography scanner at baseline (2000–2001) and 10 years later (2010-2011). CAC progression was assessed for each individual as the difference of logarithmic CAC scores at follow-up and baseline (log [CAC (follow-up) + 1] - log [CAC (baseline) + 1]). FG variability was defined by the coefficient of variation about the mean FG (FG-CV), the SD of FG (FG-SD), and the average real variability of FG (FG-ARV) during 10-year follow-up. We investigated the association between FG variability and CAC progression with adjustment for demographics, clinical risk factors, mean FG level, change in FG level, diabetes incidence and medication use. RESULTS After multivariable adjustment, 1-SD increment in FG-CV was associated with worse progression of CAC as demonstrated as percent change in CAC with 5.9% (incident CAC, 95% CI 1.0%, 10.7%) and 6.7% (any CAC progression, 95% CI 2.3%, 11.1%) progression during 10 years. Similar findings were also observed in FG-SD and FG-ARV. CONCLUSIONS Higher FG variability during young adulthood was associated with greater CAC progression in middle age, suggesting its value in predicting risk for subclinical coronary artery diseases.

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Long-Term Glycemic Variability and Vascular Complications in Type 2 Diabetes: Post Hoc Analysis of the FIELD Study

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgaa361 ◽

2020 ◽

Vol 105 (10) ◽

pp. e3638-e3649 ◽

Cited By ~ 1

Author(s):

Emma S Scott ◽

Andrzej S Januszewski ◽

Rachel O’Connell ◽

Gregory Fulcher ◽

Russell Scott ◽

...

Keyword(s):

Type 2 Diabetes ◽

Fasting Glucose ◽

Microvascular Complications ◽

Vascular Complications ◽

Total Mortality ◽

Glycemic Variability ◽

Increased Risk ◽

Post Hoc

Abstract Aims To investigate whether long-term glycemic variability (GV) is associated with vascular complication development in type 2 diabetes. Methods In a post hoc FIELD trial analysis, GV was calculated as the standard deviation and coefficient of variation (CV) of glycated hemoglobin A1c (HbA1c) and fasting plasma glucose. Baseline variables were compared across quartiles of on-study variability by chi square and ANOVA. Prospective associations between baseline to 2-year GV and subsequent vascular and mortality outcomes were analyzed using landmark logistic and Cox proportional hazards regression. Results Baseline factors associated with higher on-study GV included younger age, male gender, longer diabetes duration, and higher pharmacological therapies usage. Both HbA1c and fasting glucose CV were associated with increased risk of microvascular complications (HR 1.02 [95% CI, 1.01-1.03] P < 0.01; and HR 1.01 [95% CI, 1.00-1.01] P < 0.001, respectively). HbA1c and fasting glucose CV were associated with increased cardiovascular disease (HR 1.02 [95% CI, 1.00-1.04]; and HR 1.01 [95% CI, 1.00-1.02], both P < 0.05). HbA1c CV associated with increased stroke (HR 1.03 [95% CI, 1.01-1.06) P < 0.01). Glucose CV associated with increased coronary events (HR 1.01 [95% CI, 1.00-1.02] P < 0.05). Both HbA1c and glucose CV associated with increased total mortality (HR 1.04 [95% CI, 1.02-1.06]; and HR 1.01 [95% CI, 1.01-1.02], both P < 0.001) and noncardiovascular mortality (HR 1.05 [95% CI, (1.03-1.07]; and HR 1.02 [95% CI, 1.01-1.03], both P < 0.001). HbA1c CV associated with coronary mortality (HR 1.04 [95% CI, 1.01-1.07] P < 0.05). Conclusions Long-term GV was associated with increased risk of vascular outcomes in type 2 diabetes.

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Hyperglycemia, hypoglycemia and glycemic variability in the elderly: a fatal triad?

Monaldi Archives for Chest Disease ◽

10.4081/monaldi.2015.726 ◽

2016 ◽

Vol 84 (1-2) ◽

Author(s):

Matteo Monami ◽

Sara Aleffi

Keyword(s):

Diabetes Mellitus ◽

Cardiovascular Risk ◽

Weight Gain ◽

Microvascular Complications ◽

Glycemic Variability ◽

Glucose Variability ◽

Review Literature ◽

Morbidity And Mortality ◽

Diabete Mellito ◽

Cardiovascular Morbidity And Mortality

Diabetes mellitus is one of the most important causes of cardiovascular morbidity and mortality; the incidence of chronic complications of diabetes appears to be closely related to the degree of hyperglycaemia. However, results of clinical trials showed that intensive treatment of hyperglycaemia prevents microvascular complications, but has little or no effect on the incidence of cardiovascular events. Different hypoglycaemic drugs show different effects on cardiovascular risk. However, those trials have shown a neutral effect on cardiovascular mortality. This paradoxical result could be explained with the frequent use, in the past, of glucose-lowering agents capable of increasing the risk of hypoglicemia, glycemic variability and weight gain. In conclusion, an adequate glycemic control, in particular in elderly patients, should be achieved, whenever possible, using agents not inducing hypogycemia, glucose fluctuations, and weight gain. In fact, hypoglycaemia and glucose variability should be considered as independent cardiovascular risk factors to a similar extent to hyperglycemia. In this article, the author will review literature supporting the hypothesis that hyperglycemia, hypoglycaemia and glycemic variability are a fatal triad capable of increasing morbidity and mortality in patients with diabetes mellitus. RiassuntoIl diabete mellito è una delle più importanti cause di morbilità e mortalità cardiovascolare, ed è stata dimostrata una stretta correlazione tra compenso glicometabolico ed incidenza di complicanze croniche del diabete mellito. Tuttavia, negli studi di intervento, il controllo accurato dell’iperglicemia sembra poter prevenire le complicanze microvascolari, ma ha effetti soltanto marginali sull’incidenza di eventi cardiovascolari secondari a malattia macrovascolare. Inoltre, i grandi trial di intervento hanno mostrato come la riduzione degli eventi cardiovascolari non si accompagni ad una riduzione della mortalità cardiovascolare. Tale paradosso potrebbe essere spiegato dal fatto che spesso, in passato, per ottenere un miglioramento glicometabolico si sono utilizzati farmaci ipoglicemizzanti in grado di aumentare il rischio ipoglicemico, la variabilità glicemica ed il peso corporeo. In conclusione, il miglioramento del compenso glicemico, specie nel paziente anziano, dovrebbe essere ottenuto, quando possibile, con farmaci a basso rischio ipoglicemico e non inducenti aumenti di peso, per evitare gli effetti negativi di ipoglicemie e eccessive fluttuazioni della glicemia che di per sé costituiscono dei fattori di rischio cardiovascolari al pari dell’iperglicemia. In questo articolo, si esplorerà l’ipotesi che iperglicemia, ipoglicemia e variabilità glicemica costituiscano una triade fatale in grado di aumentare morbilità e mortalità nei pazienti affetti da diabete mellito.

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Meta-Analysis: Association Between Hypoglycemia and Serious Adverse Events in Older Patients Treated With Glucose-Lowering Agents

Frontiers in Endocrinology ◽

10.3389/fendo.2021.571568 ◽

2021 ◽

Vol 12 ◽

Author(s):

Katharina Mattishent ◽

Yoon K. Loke

Keyword(s):

Adverse Events ◽

Older Patients ◽

Meta Analysis ◽

Microvascular Complications ◽

Cardiovascular Death ◽

Vascular Events ◽

Serious Adverse Events ◽

Glucose Lowering ◽

Time Period ◽

Meta Analyses

AimsWe conducted a meta-analysis of serious adverse events (dementia, macro- and micro-vascular events, falls and fractures, and death) associated with hypoglycemia in older patients treated with glucose lowering drugs.Materials and MethodsMeta-analysis of studies reporting on hypoglycemia and adverse events. The search included studies from two previously published systematic reviews, and an updated search of MEDLINE and EMBASE from April 2014 to November 2019. We assessed study validity based on ascertainment of hypoglycemia, adverse events and adjustment for confounders, and conducted a random effects meta-analyses, assessing heterogeneity using the I2 statistic.ResultsWe included 44 studies involving 2,507,434 participants. Most of the studies used adjusted analysis for confounders and hypoglycaemic events were typically identified based on healthcare databases (severe events). Hypoglycemia was associated with increased likelihood of death in a meta-analysis of eighteen studies, pooled OR 2.02 (95% Confidence Interval 1.75–2.32). Studies assessing mortality signal a time-response relationship with a higher risk of adverse events occurring within the first 90 days after hypoglycemia. Our meta-analysis of nine studies demonstrated that hypoglycaemic episodes were associated with dementia – pooled OR 1.50 (95% CI 1.29–1.74). Our meta-analysis of nineteen studies demonstrated associations between hypoglycaemia and macrovascular complications, pooled OR 1.81 (95% CI 1.70–1.94), and microvascular complications (two studies) pooled OR 1.77 (95% CI 1.49–2.10). There is also an association between hypoglycemia and cardiovascular death (six studies) – pooled OR 2.11 (95% CI 1.55 to 2.87). Similarly, our meta-analysis of six studies demonstrated an association between hypoglycemia and falls and fractures, pooled OR 1.78 (95% CI 1.44–2.21) and 1.68 (95% CI 1.37–2.07) respectively.ConclusionThis meta-analysis confirms previously reported concerns of serious harm following hypoglycemia, especially in the immediate time period after a hypoglycaemic event. Avoidance of hypoglycaemic episodes should be a priority in this vulnerable population.

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