Dataset Information

HbA_1c variability associated with dementia risk in people with type 2 diabetes.

ABSTRACT:

Introduction

Although poor glycemic control is associated with dementia, it is unknown if variability in glycemic control, even in those with optimal glycosylated hemoglobin A_1c (HbA_1c) levels, increases dementia risk.

Methods

Among 171,964 people with type 2 diabetes, we evaluated the hazard of dementia association with long-term HbA_1c variability using five operationalizations, including standard deviation (SD), adjusting for demographics and comorbidities.

Results

The mean baseline age was 61 years (48% women). Greater HbA_1c SD was associated with greater dementia hazard (adjusted hazard ratio = 1.15 [95% confidence interval: 1.12, 1.17]). In stratified analyses, higher HbA_1c SD quintiles were associated with greater dementia hazard among those with a mean HbA_1c < 6% (P = 0.0004) or 6% to 8% (P < 0.0001) but not among those with mean HbA_1c ≥ 8% (P = 0.42).

Discussion

Greater HbA_1c variability is associated with greater dementia risk, even among those with HbA_1c concentrations at ideal clinical targets. These findings add to the importance and clinical impact of recommendations to minimize glycemic variability.

Highlights

We observed a cohort of 171,964 people with type 2 diabetes (mean age 61 years). This cohort was based in Northern California between 1996 and 2018. We examined the association between glycosylated hemoglobin A_1c (HbA_1c) variability and dementia risk. Greater HbA_1c variability was associated with greater dementia hazard. This was most evident among those with normal-low mean HbA_1c concentrations.

SUBMITTER: Moran C

PROVIDER: S-EPMC11350038 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature

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Publications

HbA<sub>1c</sub> variability associated with dementia risk in people with type 2 diabetes.

Moran Chris C Whitmer Rachel A RA Dove Zoe Z Lacy Mary E ME Soh Yenee Y Tsai Ai-Lin AL Quesenberry Charles P CP Karter Andrew J AJ Adams Alyce S AS Gilsanz Paola P

Alzheimer's & dementia : the journal of the Alzheimer's Association 20240703 8

<h4>Introduction</h4>Although poor glycemic control is associated with dementia, it is unknown if variability in glycemic control, even in those with optimal glycosylated hemoglobin A<sub>1c</sub> (HbA<sub>1c</sub>) levels, increases dementia risk.<h4>Methods</h4>Among 171,964 people with type 2 diabetes, we evaluated the hazard of dementia association with long-term HbA<sub>1c</sub> variability using five operationalizations, including standard deviation (SD), adjusting for demographics and com ...[more]

PMID: 38959429

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Project description:Aims/hypothesisMinimal evidence supports the efficacy of flash monitoring in lowering HbA1c. We sought to assess the impact of introducing flash monitoring in our centre.MethodsWe undertook a prospective observational study to assess change in HbA1c in 900 individuals with type 1 diabetes following flash monitoring (comparator group of 518 with no flash monitoring). Secondary outcomes included changes in hypoglycaemia, quality of life, flash monitoring data and hospital admissions.ResultsThose with baseline HbA1c ≥58 mmol/mol (7.5%) achieved a median -7 mmol/mol (interquartile range [IQR] -13 to -1) (0.6% [-1.2 to -0.1]%) change in HbA1c (p < 0.001). The percentage achieving HbA1c <58 mmol/mol rose from 34.2% to 50.9% (p < 0.001). Median follow-up was 245 days (IQR 182 to 330). Individuals not using flash monitoring experienced no change in HbA1c across a similar timescale (p = 0.508). Higher HbA1c (p < 0.001), younger age at diagnosis (p = 0.003) and lower social deprivation (p = 0.024) were independently associated with an HbA1c fall of ≥5 mmol/mol (0.5%). More symptomatic (OR 1.9, p < 0.001) and asymptomatic (OR 1.4, p < 0.001) hypoglycaemia was reported after flash monitoring. Following flash monitoring, regimen-related and emotional components of the diabetes distress scale improved although the proportion with elevated anxiety (OR 1.2, p = 0.028) and depression (OR 2.0, p < 0.001) scores increased. Blood glucose test strip use fell from 3.8 to 0.6 per day (p < 0.001). Diabetic ketoacidosis admissions fell significantly following flash monitoring (p = 0.043).Conclusions/interpretationFlash monitoring is associated with significant improvements in HbA1c and fewer diabetic ketoacidosis admissions. Higher rates of hypoglycaemia may relate to greater recognition of hitherto unrecognised events. Impact upon quality of life parameters was mixed but overall treatment satisfaction was overwhelmingly positive.

Project description:BackgroundPatients with type 2 diabetes are under substantially higher risk of in-stent restenosis (ISR) after coronary stent implantation. We sought to investigate whether visit-to-visit HbA1c variability is a potential predictor of ISR in diabetic patients after stent implantation.MethodsWe consecutively enrolled type 2 diabetic patients who underwent successful elective percutaneous coronary intervention and performed follow-up coronary angiography after around 12 months. The incidence of ISR and its relationship with visit-to-visit HbA1c variability, expressed as coefficient of variation (CV), standard deviation (SD) and variability independent of the mean (VIM), were studied. Multivariable Cox proportional hazards models were constructed to analyze the predictive value of HbA1c variability for ISR.ResultsFrom September 2014 to July 2018 in Ruijin Hospital, a total of 420 diabetic patients (688 lesions) after stent implantation were included in the final analysis. During a mean follow-up of 12.8 ± 1.3 months, the incidence of ISR was 8.6%, which was significantly increased in patients with higher CV of HbA1c (P = 0.001). The mean diameter stenosis (DS), net luminal loss and net luminal gain were 22.9 ± 16.8%, 0.42 ± 0.88 mm and 1.66 ± 0.83 mm, respectively. Greater DS was observed in subjects with higher tertiles of CV of HbA1c (P < 0.001), and this trend was more prominent in patients with optimal glycemic control (HbA1c ≤ 7%) in the baseline. In multivariate analysis, HbA1c variability was independently associated with incidence of ISR after adjustment for traditional risk factors and mean HbA1c (HR: 3.00 [95% CI 1.14-7.92] for highest vs. lowest tertile). Inclusion of CV of HbA1c led to a better risk stratification accuracy. Assessing HbA1c variability by SD or VIM yielded similar findings.ConclusionsThis study suggests that visit-to-visit HbA1c variability is an independent predictor of incidence of ISR in patients with type 2 diabetes after stent implantation. Trial registration NCT02089360: NCT.

Project description:Aims/hypothesisThe role of HbA1c variability in the progression of diabetic kidney disease is unclear, with most studies to date performed in White populations and limited data on its role in predicting advanced kidney outcomes. Our aim was to evaluate if long-term intra-individual HbA1c variability is a risk factor for kidney disease progression (defined as an eGFR decline of ≥50% from baseline with a final eGFR of <30 ml/min per 1.73 m2) in an ethnically heterogeneous cohort of people with type 1 diabetes with a preserved eGFR ≥45 ml/min per 1.73 m2 at baseline.MethodsElectronic health record data from people attending outpatient clinics between 2004 and 2018 in two large university hospitals in London were collected. HbA1c variability was assessed using three distinct methods: (1) SD of HbA1c (SD-HbA1c); (2) visit-adjusted SD (adj-HbA1c): SD-HbA1c/√n/(n-1), where n is the number of HbA1c measurements per participant; and (3) CV (CV-HbA1c): SD-HbA1c/mean-HbA1c. All participants had six or more follow-up HbA1c measurements. The eGFR was measured using the Chronic Kidney Disease Epidemiology Collaboration equation and clinical/biochemical results from routine care were extracted from electronic health records.ResultsIn total, 3466 participants (50% female, 78% White, 13% African Caribbean, 3% Asian and 6% of mixed heritage or self-reporting as 'other') were followed for a median (IQR) of 8.2 (4.2-11.6) years. Of this cohort, 249 (7%) showed kidney disease progression. Higher HbA1c variability was independently associated with a higher risk of kidney disease progression, with HRs (95% CIs) of 7.76 (4.54, 13.26), 2.62 (1.75, 3.94) and 5.46 (3.40, 8.79) (lowest vs highest HbA1c variability quartile) for methods 1-3, respectively. Increasing age, baseline HbA1c, systolic BP and urinary albumin/creatinine ratio were also associated with kidney disease progression (p<0.05 for all). African Caribbean ethnicity was associated with an increased risk of kidney disease progression (HR [95% CI] 1.47 [1.09, 1.98], 1.76 [1.32, 2.36] and 1.57 [1.17, 2.12] for methods 1-3, respectively) and this effect was independent of glycaemic variability and other traditional risk factors.Conclusions/interpretationWe observed an independent association between HbA1c variability, evaluated using three distinct methods, and significant kidney disease progression in a multi-ethnic type 1 diabetes cohort. Further studies are needed to elucidate the mechanisms that may explain our results and evaluate if HbA1c variability is a modifiable risk factor for preventing diabetic kidney disease progression.

Project description:Aims/hypothesisRetinal microvascular diameters are biomarkers of cardio-metabolic risk. However, the association of (pre)diabetes with retinal microvascular diameters remains unclear. We aimed to investigate the association of prediabetes (impaired fasting glucose or impaired glucose tolerance) and type 2 diabetes with retinal microvascular diameters in a predominantly white population.MethodsIn a population-based cohort study with oversampling of type 2 diabetes (N = 2876; n = 1630 normal glucose metabolism [NGM], n = 433 prediabetes and n = 813 type 2 diabetes, 51.2% men, aged 59.8 ± 8.2 years; 98.6% white), we determined retinal microvascular diameters (measurement unit as measured by retinal health information and notification system [RHINO] software) and glucose metabolism status (using OGTT). Associations were assessed with multivariable regression analyses adjusted for age, sex, waist circumference, smoking, systolic blood pressure, lipid profile and the use of lipid-modifying and/or antihypertensive medication.ResultsMultivariable regression analyses showed a significant association for type 2 diabetes but not for prediabetes with arteriolar width (vs NGM; prediabetes: β = 0.62 [95%CI -1.58, 2.83]; type 2 diabetes: 2.89 [0.69, 5.08]; measurement unit); however, there was a linear trend for the arteriolar width across glucose metabolism status (p for trend = 0.013). The association with wider venules was not statistically significant (prediabetes: 2.40 [-1.03, 5.84]; type 2 diabetes: 2.87 [-0.55, 6.29], p for trend = 0.083; measurement unit). Higher HbA1c levels were associated with wider retinal arterioles (standardised β = 0.043 [95% CI 0.00002, 0.085]; p = 0.050) but the association with wider venules did not reach statistical significance (0.037 [-0.006, 0.080]; p = 0.092) after adjustment for potential confounders.Conclusions/interpretationType 2 diabetes, higher levels of HbA1c and, possibly, prediabetes, are independently associated with wider retinal arterioles in a predominantly white population. These findings indicate that microvascular dysfunction is an early phenomenon in impaired glucose metabolism.

Project description:Aims/hypothesisWe assessed the real-world effect of flash monitor (FM) usage on HbA1c levels and diabetic ketoacidosis (DKA) and severe hospitalised hypoglycaemia (SHH) rates among people with type 1 diabetes in Scotland and across sociodemographic strata within this population.MethodsThis study was retrospective, observational and registry based. Using the national diabetes registry, 14,682 individuals using an FM at any point between 2014 and mid-2020 were identified. Within-person change from baseline in HbA1c following FM initiation was modelled using linear mixed models accounting for within-person pre-exposure trajectory. DKA and SHH events were captured through linkage to hospital admission and mortality data. The difference in DKA and SHH rates between FM-exposed and -unexposed person-time was assessed among users, using generalised linear mixed models with a Poisson likelihood. In a sensitivity analysis, we tested whether changes in these outcomes were seen in an age-, sex- and baseline HbA1c-matched sample of non-users over the same time period.ResultsPrevalence of ever-FM use was 45.9% by mid-2020, with large variations by age and socioeconomic status: 64.3% among children aged <13 years vs 32.7% among those aged ≥65 years; and 54.4% vs 36.2% in the least-deprived vs most-deprived quintile. Overall, the median (IQR) within-person change in HbA1c in the year following FM initiation was -2.5 (-9.0, 2.5) mmol/mol (-0.2 [-0.8, 0.2]%). The change varied widely by pre-usage HbA1c: -15.5 (-31.0, -4.0) mmol/mol (-1.4 [-2.8, -0.4]%) in those with HbA1c > 84 mmol/mol [9.8%] and 1.0 (-2.0, 5.5) mmol/mol (0.1 [-0.2, 0.5]%) in those with HbA1c < 54 mmol/mol (7.1%); the corresponding estimated fold change (95% CI) was 0.77 (0.76, 0.78) and 1.08 (1.07, 1.09). Significant reductions in HbA1c were found in all age bands, sexes and socioeconomic strata, and regardless of prior/current pump use, completion of a diabetes education programme or early FM adoption. Variation between the strata of these factors beyond that driven by differing HbA1c at baseline was slight. No change in HbA1c in matched non-users was observed in the same time period (median [IQR] within-person change = 0.5 [-5.0, 5.5] mmol/mol [0.0 (-0.5, 0.5)%]). DKA rates decreased after FM initiation overall and in all strata apart from the adolescents. Estimated overall reduction in DKA event rates (rate ratio) was 0.59 [95% credible interval (CrI) 0.53, 0.64]) after FM vs before FM initiation, accounting for pre-exposure trend. Finally, among those at higher risk for SHH, estimated reduction in event rates was rate ratio 0.25 (95%CrI 0.20, 0.32) after FM vs before FM initiation.Conclusions/interpretationFM initiation is associated with clinically important reductions in HbA1c and striking reduction in DKA rate. Increasing uptake among the socioeconomically disadvantaged offers considerable potential for tightening the current socioeconomic disparities in glycaemia-related outcomes.

Dataset Information

HbA_1c variability associated with dementia risk in people with type 2 diabetes.

Introduction

Methods

Results

Discussion

Highlights

Publications

HbA<sub>1c</sub> variability associated with dementia risk in people with type 2 diabetes.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

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Dataset Information

HbA1c variability associated with dementia risk in people with type 2 diabetes.

Introduction

Methods

Results

Discussion

Highlights

Publications

HbA&lt;sub&gt;1c&lt;/sub&gt; variability associated with dementia risk in people with type 2 diabetes.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

HbA_1c variability associated with dementia risk in people with type 2 diabetes.

HbA<sub>1c</sub> variability associated with dementia risk in people with type 2 diabetes.