Long-term Glycemic Variability Research Articles

124-OR: HbA1c Variability Is Independently Associated with Lower-Extremity Amputation and Death among Patients with Diabetic Foot Ulcers

Background: Higher HbA1c on admission is associated with increased amputation risk in patients with diabetic foot ulcers (DFUs) ; however, the impact of long-term glycemic control and glycemic variability after hospital discharge on amputation risk is unclear. Methods: We performed retrospective analyses of hospitalized patients with a DFU who were followed for >1 year after index admission with at least two HbA1c measurements and > 1-year follow-up (n=479) . Using multivariable logistic regression analysis, we examined the associations of HbA1c measures [HbA1c nadir change (difference between the baseline HbA1c and the single lowest prospective HbA1c level during the follow-up) , standard deviation (SD-HbA1c) , mean HbA1c change, and HbA1c variability score (HVS) ] with a composite outcome [minor and major lower extremity amputations (LEA) and mortality]. Results: The median age was 55.3 (IQR: 47.9, 62.8) years. During a mean follow-up of 2.4 years, 250 (52.2%) patients had a LEA or death [minor LEA: 116 (24.2%) ; major LEA: 113 (23.4%) ; death: 21 (4.4%) ]. In the fully adjusted model, HbA1c variability metrics were significantly associated with higher LEA and/or death rates, except HVS (Table) . Conclusion: Our findings indicate that visit-to-visit HbA1c variability, especially HbA1c nadir change, and SD-HbA1c are independent biomarkers of LEA risk in patients with DFU. Disclosure R.Jagannathan: None. M.Schechter: None. J.A.Alvarez: None. G.Blanco: None. R.Rajani: None. G.Santamarina: None. G.E.Umpierrez: Research Support; AstraZeneca, Dexcom, Inc., Novo Nordisk. M.Fayfman: None. Funding Emory Medical Care Foundation to MCS and MF

Impact of anxiety, depression and disease-related distress on long-term glycaemic variability among subjects with Type 1 diabetes mellitus

BackgroundAnxiety, depression, and disease-related distress are linked to worse overall glycaemic control, in terms of HbA1c. This study was aimed to evaluate whether traits of these emotional disorders are associated with long-term glycaemic variability in subjects with Type 1 diabetes.MethodsLongitudinal retrospective study. Six-year HbA1c data (2014–2019) from 411 subjects with Type 1 diabetes who had participated in a previous study to design a diabetes-specific quality of life questionnaire in the year 2014 were included. Scores for Spanish versions of the Hospital Anxiety and Depression Scale (HADS) and Problem Areas in Diabetes (PAID) scale were obtained at baseline, along with sociodemographic and clinical data. Long-term glycaemic variability was measured as the coefficient of variation of HbA1c (HbA1c-CV). The association between HADS and PAID scores and HbA1c-CV was analysed with Spearman correlations and multiple regression models, both linear and additive, including other covariates (age, sex, diabetes duration time, type of treatment, baseline HbA1c, use of anxiolytic or antidepressant drugs, education level and employment status).ResultsScores of depression, anxiety and distress were positively and significantly correlated to HbA1c-CV in univariate analyses. Multiple regression study demonstrated an independent association only for diabetes distress score (p < 0.001). Age, diabetes duration time, baseline HbA1c, education level and employment status were also significantly associated with HbA1c-CV. However, when subjects were analyzed separately in two age groups, distress scores were associated with HbA1c-CV only among those aged 25 years or older, while anxiety scores, but not distress, were associated with HbA1c-CV among those younger than 25 years.ConclusionsPsychological factors, particularly disease-related distress and anxiety, are associated with long-term glycaemic variability in subjects with Type 1 diabetes.

Association Between Long-Term HbA1c Variability and Functional Limitation in Individuals Aged Over 50 Years: A Retrospective Cohort Study.

BackgroundAs mean HbA1c provides incomplete information regarding glycemic variability, there has been considerable interest in the emerging association between glycemic variability and macrovascular events and with microvascular complications and mortality in adults with and without diabetes. However, the association between long-term glycemic variability, represented by visit-to-visit HbA1c variability, and functional limitations has not been clarified in previous literature. The present study aimed to explore the longitudinal association between long-term glycemic variability, represented by visit-to-visit HbA1c variability and functional limitations.MethodsThis cohort study included adults aged over 50 years who participated in the 2006 to 2016 waves of the Health and Retirement Study. Physical functions, including mobility, large muscle function, activities of daily living (ADLs), and instrumental ADLs (IADLs), were assessed at baseline and every 2 years, and HbA1c levels were assessed at baseline and every 4 years. Visit-to-visit HbA1c variability was calculated using the HbA1c variability score (HVS) during the follow-up period. Generalized estimating equation models were used to evaluate the longitudinal association between HbA1c variability and functional limitations with adjustment for a series of confounders.ResultsA total of 5,544 participants having three HbA1c measurements from 2006 to 2016, having two or more physical function measures (including one at baseline), and age over 50 years were included in this analysis. The mean age at baseline was 66.13 ± 8.39 years. A total of 916 (16.5%) participants had an HVS = 100, and 35.1% had an HVS = 50. The highest HVS category (HVS =100) was associated with increased functional status score (β = 0.093, 95% CI: 0.021–0.165) in comparison with the lowest HVS category (HVS = 0). Sensitivity analyses using the CV and SD of HbA1c as measures of variability showed similar associations between HbA1c variability and functional limitation. An incremental increase in HbA1c-CV (β = 0.630, 95% CI: 0.127–1.132) or HbA1c-SD (β = 0.078, 95% CI: 0.006–0.150) was associated with an increase in functional limitation in the fully adjusted model. ConclusionsHbA1c variability was associated with heightened difficulty in performing functional activities over time after adjusting for mean HbA1c levels and multiple demographics and comorbidities. This study provides further evidence regarding the detrimental effect of HbA1c variability and highlights the significance of steady glycemic control.

An Operations Approach for Reducing Glycemic Variability: Evidence from a Primary Care Setting

Problem definition: Diabetes is a highly prevalent and expensive chronic disease that affects millions of Americans and is associated with multiple comorbidities. Clinical research has found long-term variation in a patient’s glycated hemoglobin levels to be linked with adverse health outcomes, such as increased hospitalizations. Consequently, there is a need for innovative approaches to reduce long-term glycemic variability and efficient ways to implement them. Academic/practical relevance: Although the operations literature has extensively explored ways to manage variability across patients, relatively little attention has been paid to within-patient variability. We draw on the management and healthcare literatures to hypothesize and then show that a key operational lever—continuity of care (CoC)—can be used to reduce glycemic variability, which in turn, improves patient health. In the process, we explore the moderating role of a key demographic characteristic: patient’s marital status. We also shed light on an important mechanism through which CoC reduces variability—adherence of patients to prescribed medications—thereby advancing the compliance literature. Academically, our study adds to the understanding of the importance of managing variability (via continuity in service) in settings where customers repeatedly interact with service providers. Methodology: We use a detailed and comprehensive data set from the Veterans Health Administration, the largest integrated healthcare delivery system in the United States. This permits us to control for potential sources of heterogeneity. We analyze more than 300,000 patients—over an 11-year period—with diabetes, a chronic disease whose successful management requires managing glycemic variability. We use an empirical approach to, first, quantify the relationship between CoC and glycemic variability and second, show how this relationship differs based on patient’s marital status. Third, we estimate the mediation effect of patients’ adherence to medications. Finally, we quantify how glycemic variability mediates the relationship between CoC and three important outcomes. Our findings are validated by extensive robustness checks and sensitivity analyses. Results: We find that CoC is related to reductions in glycemic variability, more so for patients who are not married. However, this reduction is not linear in continuity; we find evidence of curvilinearity but with a sufficiently high stationary point so that benefits almost always accrue, albeit at a diminishing rate. Additionally, we find that one mechanism through which CoC may reduce variability is through patients’ adherence to medications. We also find evidence of partial mediation for glycemic variability in the CoC outcomes process chain. Our counterfactual analysis reveals the extent of improvement that enhanced continuity can bring, depending on where it is targeted. Managerial implications: Identifying the process measures through which continuity of care reduces variability is of interest to practitioners and policy makers as it can help design appropriate policies and pathways in terms of both processes and staffing/work allocation.

Long-Term Glycemic Variability and Risk of Cardiovascular Events in Type 2 Diabetes: A Meta-Analysis.

Long-term glycemic fluctuation has been associated with cardiovascular risk in patients with type 2 diabetes mellitus (T2DM). However, the findings are inconsistent. We performed a meta-analysis to summarize the association between parameters of long-term glycemic variability and risk of cardiovascular events in T2DM patients. Medline, Embase, and Web of Science databases were searched for longitudinal follow-up studies comparing the incidence of cardiovascular events in T2DM patients with higher or lower long-term glycemic variability. A random-effect model incorporating the potential heterogeneity among the included studies was used to pool the results. Twelve follow-up studies with 146 653 T2DM patients were included. The mean follow-up duration was 4.9 years. Pooled results showed that compared to those with the lowest glycemic variability, patients with the highest glycemic variability had significantly increased risk of cardiovascular events, as evidenced by the standard deviation of glycated hemoglobin [HbA1c-SD: relative risk (RR)=1.44, 95% confidence interval (CI): 1.23 to 1.69, p<0.001; I2=70%], HbA1c coefficient of variation (HbA1c-CV: RR=1.46, 95% CI: 1.19 to 1.79. p<0.001; I2=83%), standard deviation of fasting plasma glucose (FPG-SD: RR=1.33, 95% CI: 1.07 to 1.65, p=0.009; I2=0%), and FPG coefficient of variation (FPG-CV: RR=1.29, 95% CI: 1.01 to 1.64, p=0.04; I2=47%). In conclusion, increased long-term glycemic variability may be an independent risk factor for cardiovascular events in T2DM patients.

Implications of fasting plasma glucose variability on the risk of incident peripheral artery disease in a population without diabetes: a nationwide population-based cohort study

BackgroundDiabetes have been known as a traditional risk factor of developing peripheral artery disease (PAD). However, the study evaluating the impact of long-term glycemic variability on the risk of developing PAD is limited, especially in a general population without diabetes.MethodsWe included 152,931 individuals without diabetes from the Korean National Health Insurance Service–Health Screening Cohort. Fasting plasma glucose (FPG) variability was measured using coefficient variance (FPG-CV), standard deviation (FPG-SD), and variability independent of the mean (FPG-VIM).ResultsA total of 16,863 (11.0%) incident cases of PAD were identified during a median follow-up of 8.3 years. Kaplan–Meier curves showed a progressively increasing risk of PAD in the higher quartile group of FPG variability than in the lowest quartile group (log rank P < 0.001). Multivariable Cox proportional hazard analysis showed the hazard ratio for PAD prevalence as 1.11 (95% CI 1.07–1.16, P < 0.001) in the highest FPG-CV quartile than in the lowest FPG-CV quartile after adjusting for confounding variables, including mean FPG. Similar degree of association was shown in the FPG-SD and FPG-VIM. In sensitivity analysis, the association between FPG variability and the risk of developing PAD persisted even after the participants were excluded based on previously diagnosed diseases, including stroke, coronary artery disease, congestive heart failure, chronic kidney disease, or current smokers or drinkers. Subgroup analysis demonstrated that the effects of FPG variability on the risk of PAD were more powerful in subgroups of younger age, regular exercisers, and those with higher income.ConclusionsIncreased long-term glycemic variability may have a significant prognostic effect for incident PAD in individuals without diabetes.Graphical

Long-term glycemic variability and risk of stroke in patients with diabetes: a meta-analysis

ObjectivesLong-term glycemic variability has been related to increased risk of vascular complication in patients with diabetes. However, the association between parameters of long-term glycemic variability and risk of stroke remains not fully determined. We performed a meta-analysis to systematically evaluate the above association.MethodsMedline, Embase, and Web of Science databases were searched for longitudinal follow-up studies comparing the incidence of stroke in diabetic patients with higher or lower long-term glycemic variability. A random-effect model incorporating the potential heterogeneity among the included studies were used to pool the results.ResultsSeven follow-up studies with 725,784 diabetic patients were included, and 98% of them were with type 2 diabetes mellitus (T2DM). The mean follow-up duration was 7.7 years. Pooled results showed that compared to those with lowest category of glycemic variability, diabetic patients with the highest patients had significantly increased risk of stroke, as evidenced by glycemic variability analyzed by fasting plasma glucose coefficient of variation (FPG-CV: risk ratio [RR] = 1.24, 95% confidence interval [CI] 1.11 to 1.39, P < 0.001; I2 = 53%), standard deviation of FPG (FPG-SD: RR = 1.16, 95% CI 1.02 to 1.31, P = 0.02; I2 = 74%), HbA1c coefficient of variation (HbA1c-CV: RR = 1.88, 95% CI 1.61 to 2.19 P < 0.001; I2 = 0%), and standard deviation of HbA1c (HbA1c-SD: RR = 1.73, 95% CI 1.49 to 2.00, P < 0.001; I2 = 0%).ConclusionsLong-term glycemic variability is associated with higher risk of stroke in T2DM patients.

Long-term glycemic variability is associated with coronary artery calcification with type 1 diabetes.

Long-term glycemic variability is associated with coronary artery calcification with type 1 diabetes.

Glycemic control is not related to cerebral small vessel disease in neurologically asymptomatic individuals with type 1 diabetes

AimsTo determine if medium- and long-term blood glucose control as well as glycemic variability, which are known to be strong predictors of vascular complications, are associated with underlying cerebral small vessel disease (cSVD) in neurologically asymptomatic individuals with type 1 diabetes.MethodsA total of 189 individuals (47.1% men; median age 40.0, IQR 33.0–45.2 years) with type 1 diabetes (median diabetes duration of 21.7, IQR 18.3–30.7 years) were enrolled in a cross-sectional retrospective study, as part of the Finnish Diabetic Nephropathy (FinnDiane) Study. Glycated hemoglobin (HbA1c) values were collected over the course of ten years before the visit including a clinical examination, biochemical sampling, and brain magnetic resonance imaging. Markers of glycemic control, measured during the visit, included HbA1c, fructosamine, and glycated albumin.ResultsSigns of cSVD were present in 66 (34.9%) individuals. Medium- and long-term glucose control and glycemic variability did not differ in individuals with signs of cSVD compared to those without. Further, no difference in any of the blood glucose variables and cSVD stratified for cerebral microbleeds (CMBs) or white matter hyperintensities were detected. Neither were numbers of CMBs associated with the studied glucose variables. Additionally, after dividing the studied variables into quartiles, no association with cSVD was observed.ConclusionsWe observed no association between glycemic control and cSVD in neurologically asymptomatic individuals with type 1 diabetes. This finding was unexpected considering the large number of signs of cerebrovascular pathology in these people after two decades of chronic hyperglycemia and warrants further studies searching for underlying factors of cSVD.

Long-Term Glycemic Variability Is Associated With Arterial Stiffness in Chinese Adults.

ObjectiveThe aim of the study was to investigate the association between the visit-to-visit variability (VVV) of fasting plasma glucose (FPG) and arterial stiffness in Chinese adults.MethodsWe performed a cohort study involving 2002 Chinese adults with no history of myocardial infarction or stroke. All the participants attended three visits (the baseline visit in 2008, the 2nd visit in 2009 and the 3rd visit in 2013). We used four measures to define the VVV of FPG across the three visits: the standard deviation (SD), the coefficient of variation (CV), the average successive variability (ASV) and the variability independent of the mean (VIM). We used brachial-ankle pulse wave velocity (ba-PWV) to measure arterial stiffness at the 2nd and the 3rd visits.ResultsCompared with the lowest tertile of all the four measurements of VVV of FPG, significantly increased levels of ba-PWV change, ratio of ba-PWV change and the occurrence of the elevated ba-PWV were found in the highest tertile. The odds ratio (OR) and 95% confidence interval (CI) comparing participants in the highest tertile vs. the lowest tertile of FPG-SD was 1.37 (1.01-1.86) for risks of having elevated ba-PWV, even after adjustment for covariates including the mean FPG. Similar results were found for FPG-CV and FPG-VIM.ConclusionGreater long-term variability of FPG was associated with an increased risk of arterial stiffness, suggesting that the VVV of FPG could be used for an early detection of subclinical atherosclerosis.

Association between visit-to-visit variability of glycated albumin and diabetic retinopathy among patients with type 2 diabetes - A prospective cohort study.

There is a paucity of studies regarding the association between long-term glycemic variability with the risk of diabetic retinopathy (DR) in patients with type 2 diabetes. Therefore, the purpose of this study is to explore the association of glycated albumin (GA) variability and HbA1c variability with the risk of DR in patients with type 2 diabetes. This prospective cohort study included 315 inpatients with type 2 diabetes (191 males and 124 females) with at least 3 measurements of GA and HbA1c within 2years prior to the baseline investigation. Different GA and HbA1c variability markers were calculated, including CV, variability independent of the mean (VIM), and the average real variability (ARV). Cox proportional hazard regression models were used to explore the association between visit-to-visit variability of GA and HbA1c and the risk of DR. After an average follow-up of 3.42years, 81 patients developed incident DR. Multivariable-adjusted (diabetes duration, smoking status, systolic blood pressure, albumin to creatinine ratio, triglycerides, using fibrates, and mean HbA1c) hazard ratios of DR associated with each unit increase in GA-CV, GA-VIM, and GA-ARV were 1.05 (95% CI 1.02-1.09), 1.69 (95% CI 1.24-2.32), and 1.13 (95%CI 1.04-1.23), respectively. However, there was no significant association between visit-to-visit HbA1c variability and the risk of DR. The present study indicated that visit-to-visit variability of GA can predict the risk of incident DR in patients with type 2 diabetes, and the prediction ability is independent of the average HbA1c levels.

Association of visit-to-visit glycemic variability with risk of cardiovascular diseases in high-risk Japanese patients with type 2 diabetes: A subanalysis of the EMPATHY trial.

Aims/IntroductionLong‐term glycemic variability is important for predicting diabetic complications, but evaluation in a Japanese population is lacking. The aim of this study was to explore the relationship between visit‐to‐visit glycemic variability (VVV) and cardiovascular diseases (CV) in Japanese patients with type 2 diabetes, using the prospective cohort of the EMPATHY trial.Materials and MethodsAmong 4532 participants with at least three HbA1c measurements, VVV was defined using the coefficient of variation (CV‐HbA1c). The outcomes were the composite cardiovascular endpoints, including cardiac, cerebral, renal, and vascular events. The odds ratios (ORs) for the development of outcomes were estimated by using logistic regression models.ResultsDuring a median follow‐up of 38 months, 190 subjects developed CV events. The risk of developing CV events increased significantly with increasing quintile of CV‐HbA1c, after multivariable adjustment including the mean‐HbA1c (OR for the fifth vs first quintile, 1.73; 95%CI, 1.03–2.91; P for trend test = 0.003). There was a stronger association between CV‐HbA1c and CV events in patients with a mean‐HbA1c of <7% compared with those with a mean‐HbA1c of ≥7% (OR per 1 standard deviation, 1.51; 95%CI, 1.23–1.85 and 1.13; 95%CI, 0.98–1.29, respectively; P for interaction = 0.02).ConclusionsIncreases of VVV were associated with the risk of CV events in Japanese patients with type 2 diabetes independent of the mean‐HbA1c. The long‐term variability of HbA1c as well as the mean HbA1c might be an important glycemic indicator in the management of patients with type 2 diabetes, especially in those with a mean‐HbA1c of <7%.

Increased Hemoglobin A1c Time in Range Reduces Adverse Health Outcomes in Older Adults With Diabetes.

Short- and long-term glycemic variability are risk factors for diabetes complications. However, there are no validated A1C target ranges or measures of A1C stability in older adults. We evaluated the association of a patient-specific A1C variability measure, A1C time in range (A1C TIR), on major adverse outcomes. We conducted a retrospective observational study using administrative data from the Department of Veterans Affairs and Medicare from 2004 to 2016. Patients were ≥65 years old, had diabetes, and had at least four A1C tests during a 3-year baseline period. A1C TIR was the percentage of days during the baseline in which A1C was in an individualized target range (6.0-7.0% up to 8.0-9.0%) on the basis of clinical characteristics and predicted life expectancy. Increasing A1C TIR was divided into categories of 20% increments and linked to mortality and cardiovascular disease (CVD) (i.e., myocardial infarction, stroke). The study included 402,043 veterans (mean [SD] age 76.9 [5.7] years, 98.8% male). During an average of 5.5 years of follow-up, A1C TIR had a graded relationship with mortality and CVD. Cox proportional hazards models showed that lower A1C TIR was associated with increased mortality (A1C TIR 0 to <20%: hazard ratio [HR] 1.22 [95% CI 1.20-1.25]) and CVD (A1C TIR 0 to <20%: HR 1.14 [95% CI 1.11-1.19]) compared with A1C TIR 80-100%. Competing risk models and shorter follow-up (e.g., 24 months) showed similar results. In older adults with diabetes, maintaining A1C levels within individualized target ranges is associated with lower risk of mortality and CVD.

91-OR: Visit-to-Visit Variability of Glycated Albumin Was Associated with the Risk of Diabetic Retinopathy in Patients with Type 2 Diabetes

Background: The association between long-term glycemic variability and diabetic retinopathy (DR) among patients with type 2 diabetes has not been clarified yet. Objective: The aim of this study was to investigate the association of visit-to-visit variability of hemoglobin A1c (HbA1c) and glycated albumin (GA) with the risk of DR in patients with type 2 diabetes. Design: A prospective cohort study of 315 patients (191 males and 124 females) with at least 3 measurements of HbA1c and GA prior to baseline was performed. Different GA and HbA1c variability markers were calculated, including coefficient of variation (CV), variability independent of the mean (VIM), and the average real variability (ARV). Cox proportional hazard regression models were used to explore the association between visit-to-visit HbA1c and GA variability and the risk of DR. Results: During a mean follow-up period of 3.42 years, 81 participants developed incident DR. Multivariate-adjusted hazard ratios (HRs) of DR across tertiles of GA-CV values were 1.00, 1.42, and 2.12 (P for trend=0.027), respectively. When we used GA-VIM and GA-ARV values as exposures, similar positive associations with the risk of DR were found. Multivariable-adjusted HRs of DR associated with each unit increase in GA-CV, GA-VIM, and GA-ARV were 1.05 (95% CI 1.02-1.09), 1.69 (95% CI 1.24-2.32), and 1.13 (95%CI 1.04-1.23), respectively. However, there was no significant association between visit-to-visit variability of HbA1c and the risk of DR after multivariate adjustment. Conclusion: The visit-to-visit variability of GA can predict the risk of incident DR in patients with type 2 diabetes, and the prediction ability is independent of the average HbA1c levels. Disclosure J. Zhou: None. D. Dai: None. Y. Shen: None. J. Lu: None. Y. Wang: None. W. Zhu: None. Y. Bao: None. G. Hu: None. Funding National Key Research and Development Project of China (2018YFC2000802); Shanghai Municipal Education Commission (20161430); Shanghai Municipal Key Clinical Specialty

Relationship between short and long-term glycemic variability and oxidative stress in type 1 diabetes mellitus under daily life insulin treatment.

The purpose of this study was to investigate the heterogeneity of the association between glycemic variability and oxidative stress markers in T1DM patients under daily life insulin treatment. We studied, in a cross-sectional analysis, 76 T1DM patients without clinical chronic diabetes complications and 22 healthy individuals. Were evaluated the short-term glycemic variability (STGV), long-term glycemic variability (LTGV), oxidative stress markers [8-isoprostaglandin-F2α (Ur-8-iso-PGF2α), nitric oxide (NO), thiobarbituric acid reactive substances (TBARS) and erythrocytes reduced/oxidized glutathione (GSH/GSSG)] and biochemical dosages (glycaemia, HbA1c, lipidogram, albuminuria). Plasmatic NO was positively associated with LTGV (last year average of HbA1c) (8.7 ± 1.6% or 71 ± 18 mmol) (rS: 0.278; p: 0.042). Plasmatic TBARS, erythrocytes GSH/GSSH and Ur-8-iso-PGF-2α didn't show correlation with glycemic variability. GSH/GSSG was inversely correlated with LDL-cholesterol (rS: - 0.417; p: 0.047) and triglycerides (rS: -0.521; p: 0.013). Albuminuria was positive correlated with age (rS: 0.340; p: 0.002), plasmatic NO (rS: 0.267; p 0.049) and TBARS (rS: 0.327; p: 0.015). In daily life insulin treatment, young T1DM patients have higher plasmatic NO than healthy subjects. However, the correlation between glycemic variability and oxidative stress markers is heterogeneous. Lipid profile and albuminuria are associated with different oxidative stress markers. These data collaborate to explain the controversial results in this issue.

Long-term Fasting Glycemic Variability and Microvascular Complications in Type 2 Diabetes.

Long-term Fasting Glycemic Variability and Microvascular Complications in Type 2 Diabetes.

Letter to the Editor from Watanabe et al: “Long-term Glycemic Variability and Vascular Complications in Type 2 Diabetes: Post Hoc Analysis of the FIELD Study”

Letter to the Editor from Watanabe et al: “Long-term Glycemic Variability and Vascular Complications in Type 2 Diabetes: Post Hoc Analysis of the FIELD Study”

Association between alterations of corneal sub-basal nerve plexus analyzed with in vivo confocal microscopy and long-term glycemic variability.

The effect of long-term glycemic variability upon corneal sub-basal nerve plexus (CSNP) morphology analyzed by in vivo confocal microscopy (IVCM) has been poorly investigated in the setting of type 1 diabetes mellitus (T1DM). Our purpose was to analyze the association between morphometric parameters of CSNP and new markers of glycemic variability in a population of patients with T1DM. Forty patients with T1DM underwent: assessment of diabetic neuropathy (DN); analysis of subcutaneous advanced glycated end-products; IVCM scans of CSNP. The fully automated software ACCMetrics was employed to analyze IVCM images and calculate seven corneal nerve parameters. Data of diabetes duration, mean and standard deviation (SD) of either last-year and all-time glycated hemoglobin (HbA1C) were retrieved. Diabetes duration and all-time SD of HbA1C were independently associated with CNFD (R = -0.26, p = 0.01; R = -0.27, p = 0.047 respectively), CNFL (R = -0.12; p = 0.01; R = -0.17, p = 0.01 respectively) and CNFrD (R = -0.001, p = 0.009; R = -0.002, p = 0.007 respectively). The analysis of the association among IVCM parameters and specific subtypes of DN showed that altered cold sensitivity was independently associated with CNFD (B = -0.24, p = 0.01), CNFL (B = -0.46, p = 0.01) and CNFrD (B = -28.65, p = 0.03). All-time SD of HbA1C and disease duration were found to be independent predictors of damage to CSNP in patients with T1DM.

Fasting plasma glucose variability in midlife and risk of Parkinson's disease: A nationwide population-based study

AimDespite the recognized association between type 2 diabetes (T2D) and Parkinson's disease (PD), the implications of glycaemic variability for patients with PD are as yet unknown. For this reason, our study assessed the future risk of incident PD according to visit-to-visit fasting plasma glucose (FPG) variability, as calculated by standard deviation (FPG-SD), coefficient variance (FPG-CV) and variability independent of the mean (FPG-VIM). MethodsUsing the Korean National Health Insurance Service Health Screening Cohort, 131,625 Korean adults without diabetes were followed. They were divided into a midlife group (age<65 years) and an elderly group (age≥65 years) throughout a median follow-up of 8.4 years. ResultsAdjusted hazard ratios (HRs) were calculated using multivariable Cox proportional-hazards analysis. In the midlife group, HRs for incident PD in the highest quartile of FPG variability (as measured by SD, CV and VIM) were 1.37 [95% confidence interval (CI): 1.09–1.73], 1.33 (95% CI: 1.06–1.68) and 1.35 (95% CI: 1.07–1.70), respectively, vs the lowest variability quartile group. However, while incident PD did not differ according to FPG variability in the elderly group, Kaplan–Meier curves of PD probability in the midlife group showed a progressively increasing risk of PD the higher the FPG variability. According to a multivariable adjusted model, every 1-SD unit increment in glycaemic variability was associated with a 9% higher risk of incident PD in the midlife group. ConclusionIncreased long-term glycaemic variability may be a precipitating risk factor for developing PD in the midlife population without diabetes.

Fasting Plasma Glucose Variability and Gastric Cancer Risk in Individuals Without Diabetes Mellitus: A Nationwide Population-Based Cohort Study.

INTRODUCTION:Long-term glycemic variability is associated with various adverse health outcomes in patients with diabetes mellitus (DM). However, the relationship between glycemic variability and gastric cancer remains unclear. We aimed to investigate the association between glycemic variability and gastric cancer incidence in individuals without DM.METHODS:We used the Korean National Health Insurance Service data sets of claims and health checkups and included 202,562 individuals without DM. Fasting plasma glucose (FPG) variability was measured using the variability independent of the mean (VIM), coefficient of variation, SD, and average successive variability. The association between FPG variability and gastric cancer incidence was analyzed using Cox regression adjusting for age, sex, body mass index, smoking status, alcohol consumption, regular exercise, income level, family history of cancer, mean FPG level, and number/mean interval of FPG measurements.RESULTS:In total, 1,920 patients developed gastric cancer (0.95%) within a median follow-up of 5.6 (5.3, 6.4) years. The fully adjusted hazard ratio and 95% confidence interval for gastric cancer were 1.26 and 1.18–1.34, respectively, in the highest quartile of FPG variability assessed by VIM compared with that in the lowest quartile. Similar results were obtained in the normal and impaired fasting glucose groups and when using the variability indexes, including coefficient of variation, SD, and average successive variability. There was a sequential increase in the incidence of gastric cancer according to the increase in the deciles of FPG variability (P for linear trend <0.001). A 1-SD increase in FPG variability assessed by VIM was significantly associated with a 10.0% increase in gastric cancer risk in the fully adjusted model.DISCUSSION:In a DM-free population, high variability in visit-to-visit FPG levels was independently associated with an increased risk of gastric cancer.