HbA1c Variability Research Articles

Progress in the Study of Glycosylated Haemoglobin Variability Index in Relation to Chronic Complications of Diabetes Mellitus

Diabetes mellitus (DM) is a common endocrine disease that can cause damage to tissues and organs throughout the body. Glycosylated haemoglobin (HbA1c) is considered to be the gold standard for assessing glycaemic control and treatment outcomes in patients with diabetes, but there is individual variability that affects the accurate interpretation of blood glucose. The glycosylated haemoglobin variability index (HGI) is a measure of individual variability in HbA1c and can be used in the management and treatment of patients with DM. In this paper, the relationship between HGI and chronic complications of DM is reviewed and discussed, with the aim of providing a more individualized and accurate reference for clinical management of blood glucose and risk assessment of chronic complications in DM patients, reducing and delaying the occurrence of chronic complications of diabetes and improving the quality of life of DM patients.

Visit-to-visit HbA1c variability is associated with aortic stiffness progression in participants with type 2 diabetes

BackgroundGlycemic variability plays an important role in the development of cardiovascular disease (CVD). This study aims to determine whether long-term visit-to-visit glycemic variability is associated with aortic stiffness progression in participants with type 2 diabetes (T2D).MethodsProspective data were obtained from 2115 T2D participants in the National Metabolic Management Center (MMC) from June 2017 to December 2022. Two brachial-ankle pulse wave velocity (ba-PWV) measurements were performed to assess aortic stiffness over a mean follow-up period of 2.6 years. A multivariate latent class growth mixed model was applied to identify trajectories of blood glucose. Logistic regression models were used to determine the odds ratio (OR) for aortic stiffness associated with glycemic variability evaluated by the coefficient of variation (CV), variability independent of the mean (VIM), average real variability (ARV), and successive variation (SV) of blood glucose.ResultsFour distinct trajectories of glycated hemoglobin (HbA1c) or fasting blood glucose (FBG) were identified. In the U-shape class of HbA1c and FBG, the adjusted ORs were 2.17 and 1.21 for having increased/persistently high ba-PWV, respectively. Additionally, HbA1c variability (CV, VIM, SV) was significantly associated with aortic stiffness progression, with ORs ranging from 1.20 to 1.24. Cross-tabulation analysis indicated that the third tertile of the HbA1c mean and VIM conferred a 78% (95% confidence interval [CI] 1.23–2.58) higher odds of aortic stiffness progression. Sensitivity analysis demonstrated that the SD of HbA1c and the highest HbA1c variability score (HVS) were significantly associated with the adverse outcomes independent of the mean of HbA1c during the follow-up.ConclusionsLong-term visit-to-visit HbA1c variability was independently associated with aortic stiffness progression, suggesting that HbA1c variability was a strong predictor of subclinical atherosclerosis in T2D participants.

1134-P: Determination of Glucose-Independent Racial Disparity in HbA1c in Youth with Type 1 Diabetes in the Era of Continuous Glucose Monitoring

Introduction: The extent and importance of higher HbA1c levels not due to mean blood glucose (MBG) in non-Hispanic Black (B) versus non-Hispanic White (W) individuals is controversial. We sought to clarify the relationship of HbA1c with metrics of glycemia derived from continuous glucose monitoring (CGM) in a young biracial population. Methods: Glycemic data of 33 B and 85 W, otherwise healthy youth with type 1 diabetes (age 14.7±4.8 years, M/F=51/67, duration of diabetes 5.4±4.7 years) was derived from a factory calibrated CGM and compared with assayed HbA1c. Hemoglobin glycation index (HGI) a metric of MBG difference in HbA1c not due to MBG =assayed HbA1c - Glucose Management Index (GMI). Results: B patients had higher unadjusted levels of HbA1c, MBG, MBGSD, GMI and HGI than W patients. Percent glucose time in range (TIR) and percent sensor use (PSU) were lower for B patients. HbA1c remained higher in B patients (8.6%) versus (7.7%) for W (p<0.0001) after statistical adjustment for MBG, MBGSD, age, gender, insulin delivery method and PSU. MBG and race accounted for 80% of the variation in HbA1c in the model. Results were similar when TIR was substituted for MBG (R2=0.64, p<0.0001). The 95% for HGI=0.47% in W patients, 52% of B patients had HGI ≥0.5%. Percent time below range was similar for both groups. Conclusions: Young B patients have clinically relevant higher HbA1c (~0.9%) at any given level of MBG or TIR than W patients, which may pose an additional risk for diabetes complications. HGI ≥0.5% may be an easy way to identify high risk patients. Disclosure N.J.Christakis: None. D.Felipe: None. R.Gomez: None. S.Chalew: Advisory Panel; Medtronic. Funding National Institutes of Health (1R21DK118643-01A1, U54GM104940)

1353-P: Glycemic Control and Longitudinal Brain MRI in Children Diagnosed with Diabetes before 3 Years of Age (CLARiFY Study)

Though early childhood onset of type 1 diabetes (T1D) is associated with brain development alterations, the affected brain regions and role of glycemic control are unknown. We aimed to examine associations between of HbA1c mean and variability and brain structure in a cohort of children diagnosed with T1D before 3 years of age. We recruited children presenting to a tertiary hospital in Australia from 1990-1992 in the Cognition and Longitudinal Assessment of Risk Factors over 30 Years (CLARiFY) Study. HbA1c was serially measured over 30 years after T1D diagnosis. Brain MRI was performed at ~12- and 30-years post diagnosis. We used linear mixed effects modelling to examine associations between mean HbA1c and HbA1c coefficient of variation and brain MRI structural measures. Data were available for 10 subjects (6 female). The mean age of diabetes diagnosis was 1.9 years. The mean HbA1c at 12- and 30-years post diagnosis was 8.5%. We did not find an association between mean HbA1c and any of the brain structures. Greater HbA1c coefficient of variation was associated with less sub-cortical gray matter volume (β=-41537, p=0.006) and greater cortical thickness (β=0.47, p=0.02) but not other brain structure measures (Table 1). In these preliminary analyses, we found HbA1c variability associated with measures of gray matter. Work is ongoing to confirm and understand the implications of these results. Disclosure C.Moran: None. O.Gbadeyan: None. A.Brown: None. S.A.Sakowski: None. V.Srikanth: None. F.Cameron: None. E.A.Northam: None. E.L.Feldman: None. R.Beare: None. Funding National Institutes of Health (R01DK129320)

795-P: Elucidating the Role of Weight Loss and Glycemia with Observed Benefits of GLP-1 Receptor Agonist Treatment in Patients with T2D

Weight loss has been associated with reduced cardiovascular disease (CVD) risk in people with type 2 diabetes (T2D). Glucagon-like peptide-1 receptor agonists (GLP-1RA) are an advancement in T2D treatment that can regulate glycemia and promote weight loss. However, the impact of weight loss, independent of glycemic control, on real-world clinical outcomes is not well understood. Here, the Cleveland Clinic electronic health record system was utilized to investigate the independent contributions of glycemic control and body mass index (BMI) change on clinical outcomes such as CVD, chronic kidney disease (CKD), hypertension, dyslipidemia, and time to insulin initiation in patients with T2D treated with GLP-1RA. Patients (n=4161) with T2D seen at the Cleveland Clinic between 8/2/2005 and 12/31/2021 who initiated GLP-1RA treatment without documented congestive heart failure, insulin use, and/or an estimated glomerular filtration rate <30 mL/min at the time of treatment initiation were retrospectively analyzed. Patients were required to be receiving GLP-1RA treatment for ≥12 months and have <18 months between physician encounters. Independent of glycemic control, each 1% reduction in BMI was associated with a 4% reduction in CVD risk (P=.008) and a 3% reduction in insulin initiation risk (P=.002). Independent of BMI change, each 1% reduction in HbA1c was associated with a 4% reduction in CKD risk (P=.001) and a 16% reduction in insulin initiation risk (P<.0001). Associations between BMI variability and CVD (HR=1.12, P<.0001) and osteoarthritis (HR=1.09, P=.014) and between HbA1c variability and CKD (HR=1.73, P=.032) and hypertension (HR=1.07, P<.0001) were observed. Durable BMI reduction was associated with a 28% decrease in CKD risk (P=.016) and a 61% reduction in hypertension risk (P=.005). In the real-world setting, decreased BMI was independently associated with reduced risk of CVD, CKD, hypertension, osteoarthritis, and insulin initiation. Disclosure A.Sharma: None. B.Burguera: Research Support; Novo Nordisk. M.Kattan: Consultant; Renalytix, Verici, Research Support; Novo Nordisk, Bayer Inc. A.D.Misra-hebert: Research Support; Bayer Inc., Merck Sharp & Dohme Corp., Novo Nordisk. K.M.Pantalone: Consultant; AstraZeneca, Bayer Inc., Corcept Therapeutics, Diasome, Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk, Sanofi, Research Support; Bayer Inc., Merck & Co., Inc., Novo Nordisk, Twin Health, Speaker's Bureau; AstraZeneca, Corcept Therapeutics, Merck & Co., Inc., Novo Nordisk. D.M.Rotroff: Research Support; Novo Nordisk, Stock/Shareholder; Clarified Precision Medicine. A.Mariam: None. E.Zacherle: None. A.Milinovich: Research Support; Novo Nordisk, Merck & Co., Inc., AbbVie Inc., Amgen Inc., Bayer Inc., Eli Lilly and Company, Twin Health. J.Bauman: None. D.S.Sugano: None. J.Noone: Employee; Novo Nordisk. J.R.Rajpura: Employee; Novo Nordisk. R.S.Zimmerman: Speaker's Bureau; Xeris Pharmaceuticals, Inc.

150-OR: Mean HbA1c and Glycaemic Variability Are Associated with Adverse Outcomes following Infrainguinal Bypass for Peripheral Arterial Disease (PAD)—A Retrospective Cohort Study

Introduction: Glycemic variability (GV) is associated with increased risk of several adverse outcomes in people with diabetes (DM). However, on the impact of GV on graft patency following infra-inguinal bypass (IIB) for peripheral arterial disease (PAD) is unknown. Methods: A 3-year single centre retrospective case notes analysis of those undergoing IIB 2017-2019. HbA1c values for 5 years pre-procedure (minimum of 3) were used to calculate a mean (±SD) HbA1c (MH) and GV. Time to re-intervention, ipsilateral amputation or death were recorded to determine primary (PP) and secondary patency (SP). Results: 193 IIB outcomes were analysed: mean (±SD) age 68.9 (9.2) years; 135 (69.9%) male. 156 (80.8%) had pre-operative HbA1c for analysis and 88 (45.6%) had DM; 87 (45.1%) were current smokers; 107 (55.4%) underwent emergency procedures. Those without diabetes were more likely to smoke (P=0.011), but those with DM had higher Rutherford stage (p<0.01), underwent more distal bypasses (p<0.01) and more emergency procedures (p=0.04). Those with DM had longer mean [IQR] hospital stays 9 [5-21] vs 7 [4-15] days (p=0.017), lower PP 335 [184-542] vs 883 [436-1437] days (p=0.04) and lower SP 751 [387-1108] vs 1079 [895-1593] days (p=0.037). Both MH and GV were associated with amputation free survival time (r=-0.232, p=0.004 and r=-0.243, p=0.011 respectively). A GV>9.1% was associated with significantly lower PP than GV<9.1%, 198[105-377] vs 713 [313-1287] days (p=0.02). On multivariate adjustment, GV >9.1% and level of bypass remained independent predictors of primary patency, HR 1.96 (95% CI:1.12-3.42, p=0.018) and HR 2.54 (95%CI:1.24-5.22, p=0.038) respectively. Conclusions: We have shown a significant relationship between MH and GV and risk of adverse outcomes in people undergoing IIB. Lowering glycemic variability should be an additional therapeutic target together with lowering mean HbA1c. Disclosure K.Dhatariya: Other Relationship; Novo Nordisk, AstraZeneca, Boehringer-Ingelheim, Eli Lilly and Company. P.C.Bennett: None. D.J.Farndon: None.

1117-P: Variability in Glycemia Measured by CGM in Children and Young Adults with Acute Recurrent or Chronic Pancreatitis

Post pancreatitis diabetes mellitus is an underrecognized disorder. Children with pancreatitis are at elevated risk for development of diabetes (DM) in the near term (approximately 9%), and lifetime risk of DM approaches 50%. Unfortunately, there is limited data regarding pathophysiology and disease course. This pilot study was undertaken to investigate glycemic physiology in the free-living state in children with acute recurrent (ARP) or chronic pancreatitis (CP). Methods: Children (<21 years of age) with an established diagnosis of CP or ARP, and participants of INSPPIRE-2 (INternational Study Group of Pediatric Pancreatitis: In search for a cuRE) were invited to participate. Pancreatitis type, demographics and growth parameters were extracted from the INSPPIRE-2 database. HbA1c was collected. A continuous glucose monitor was placed (CGM, Dexcom Pro). Glycemic variability metrics were calculated at the participant level using EasyGV software. The relationship between HbA1c and CGM variables was evaluated via multiple linear regression. Results: 12 children were enrolled, age 10-20.8 years (mean 17.2; 66% female). One subject had known DM prior to enrollment. Participants had normal mean height (0.19+/- 0.72 SD), weight (1.1 +/- 0.98SD) and BMI (0.98 +/- 0.81 SD) z-scores. Mean A1c was 5.73% (range 5.0-8.9) with the known diabetic and 5.42% (5.0-6.1) without. Mean CGM glucose was 121.8 mg/dl +/- 21.4. Of the 11 subjects without DM, 2 had CGM glucose >180 mg/dl > 10% time and 1 had CGM glucose <55 mg/dl > 1% time. HbA1c correlated with mean CGM glucose in univariate analysis and when controlled for age and BMI (p = 0.02, r2 = 0.47). Conclusions: In this small study, A1c correlated well with average CGM glucose in children with ARP and CP, and some had abnormal glycemic excursions on CGM. More research is needed on the use of CGM in children with CP and ARP. Disclosure M.G.Parra villasmil: None. M.Bellin: Consultant; Insulet Corporation, Vertex Pharmaceuticals Incorporated, Research Support; Dexcom, Inc., ViaCyte, Inc. C.Pinnaro: None. K.L.Ode: None.

#4126 LONG-TERM VISIT TO VISIT VARIABILITY IN HBA1C AND KIDNEY RELATED OUTCOMES IN PERSONS WITH DIABETES

Abstract Background and Aims Glycated hemoglobin (HbA1c) is central to the routine monitoring of glycemic control in persons with diabetes, and poor glycemic control is an established contributor to the occurrence and progression of CKD, but whether long-term visit-to-visit variability in glycemic control predicts kidney outcomes is not well studied. Method We included all adults with type 1 or type 2 diabetes in Stockholm, Sweden, during 2006–2019, who had at least one annual outpatient HbA1c test in three consecutive years. We evaluated associations between baseline and time-varying HbA1c variability score (HVS, the percentage of total HbA1c measures that vary by >0.5% [5.5 mmol/mol] during a 3-year window), with the risk of CKD progression (composite of >30% eGFR decline and kidney failure), acute kidney injury (AKI, by clinical diagnosis or increase in creatinine ≥0.3 mg/dL over 48 h or 1.5 times creatinine over 7 days), and worsening of albuminuria. Results We included 93,598 adults with diabetes undergoing 891,536 routine HbA1c tests (median 8 tests per person) during a median follow-up of 5.2 years. Compared with persons showing low HbA1c variability (HVS 0–20%), any increase in variability was associated with a higher risk of adverse kidney outcomes. For example, for patients with a baseline HbA1c variability of 81–100%, the adjusted HR was 1.47 (95% CI, 1.38-1.56) for CKD progression, 1.27 [1.19-1.36] for AKI, and 1.28 [1.21-1.36] for worsening of albuminuria. Results were robust across subgroups (diabetes subtypes, baseline eGFR or albuminuria categories) and in sensitivity analyses including time-weighted average HbA1c or alternative metrics of variability. Conclusion A higher long-term visit-to-visit HbA1c variability is robustly associated with the risks of CKD progression, AKI and worsening of albuminuria.

Relationship between Helicobacter pylori and glycated hemoglobin: a cohort study.

Helicobacter pylori (H. pylori) has increasingly been shown to be related to extragastric diseases. Glycated hemoglobin A1c (HbA1c), an indicator of glycemic control, is closely linked to the event of diabetes. The purpose of this research was to analyze the association between H. pylori and HbA1c through a cohort study. The population who underwent multiple physical checkups in the physical examination center of Taizhou Hospital was included. All of them underwent urea breath test, serological examination and physical parameter measurement. Multiple regression was used for analyzing the influencing factors of HbA1c. In addition, the result of HbA1c on H. pylori infection was studied by restricted cubic spline (RCS) analysis. The triglyceride glucose (TyG) index represents the level of insulin resistance (IR) in the population. The population was classified on the basis of primary and last H. pylori infection, therefore, the variations of HbA1c and TyG index among totally different teams were investigated. Multiple regression demonstrated that H. pylori was an influential factor in HbA1c. RCS analysis showed a nonlinear relationship between HbA1c and H. pylori infection. When HbA1c>5.7%, the chance of H. pylori infection was considerably enlarged. Additionally, long-term H. pylori infection increased HbA1c levels, while HbA1c levels decreased after H. pylori eradication. Similarly, long-term H. pylori infection also increased the TyG index. Prediabetes increases the danger of H. pylori infection, long-term H. pylori infection increases HbA1c and IR levels, and wipeout of H. pylori could have a positive impact for glycemic control in the population.

Visit-to-visit HbA1c variability, dementia, and hippocampal atrophy among adults without diabetes

ObjectivesAdults without diabetes are not completely healthy; they are probably heterogeneous with several potential health problems. The management of hemoglobin A1c (HbA1c) is crucial among patients with diabetes; but whether similar management strategy is needed for adults without diabetes is unclear. Thus, this study aimed to investigate the associations of visit-to-visit HbA1c variability with incident dementia and hippocampal volume among middle-aged and older adults without diabetes, providing potential insights into this question. MethodsWe conducted a prospective analysis for incident dementia in 10,792 participants (mean age 58.9 years, 47.8 % men) from the UK Biobank. A subgroup of 3793 participants (mean age 57.8 years, 48.6 % men) was included in the analysis for hippocampal volume. We defined HbA1c variability as the difference in HbA1c divided by the mean HbA1c over the 2 sequential visits ([latter − former]/mean). Dementia was identified using hospital inpatient records with ICD-9 codes. T1-structural brain magnetic resonance imaging was conducted to derive hippocampal volume (normalized for head size). The nonlinear and linear associations were examined using restricted cubic spline (RCS) models, Cox regression models, and multiple linear regression models. ResultsDuring a mean follow-up (since the second round) of 8.4 years, 90 (0.8 %) participants developed dementia. The RCS models suggested no significant nonlinear associations of HbA1c variability with incident dementia and hippocampal volume, respectively (All P > 0.05). Above an optimal cutoff of HbA1c variability at 0.08, high HbA1c variability (increment in HbA1c) was associated with an increased risk of dementia (Hazard Ratio, 1.88; 95 % Confidence Interval, 1.13 to 3.14, P = 0.015), and lower hippocampal volume (coefficient, −96.84 mm3, P = 0.037), respectively, in models with adjustment of covariates including age, sex, etc. Similar results were found for a different cut-off of 0. A series of sensitivity analyses verified the robustness of the findings. ConclusionsAmong middle-aged and older adults without diabetes, increasing visit-to-visit HbA1c variability was associated with an increased dementia risk and lower hippocampal volume. The findings highlight the importance of monitoring and controlling HbA1c fluctuation in apparently healthy adults without diabetes.

Association of HbA1c trajectory and variability with cognitive function

AbstractBackgroundType 2 diabetes (T2D) is an important modifiable risk factor for cognitive decline, and increasing evidence suggests that worse glucose control, in addition to a diagnosis of T2D, may play a role in cognitive function in later life. Despite this increasing concern, evidence regarding the relative contributions of poor glucose control and higher glucose variability to cognitive dysfunction among individuals with overweight or obesity is limited, mostly due to lack of repeated measures in many studies.MethodLook AHEAD MIND Study participants, aged 45‐76 years at baseline (2001‐04) with T2D and overweight or obesity, were randomized to an intensive lifestyle intervention focused on weight loss or a diabetes support and education condition, which were discontinued after ∼10 years. HbA1c levels were evaluated at years 1‐4, 6, 8, and 10. Cognitive function was evaluated up to four times between years 8‐18 with a cognitive battery that assessed memory, attention, and executive function domains. Cognitive scores were binned into four groups based on relative timing of cognitive assessments (8‐9; 10‐11; 12‐14; and 15‐18 years). We classified HbA1c variability according to: Variability Independent of the Mean (VIM), Average Real Variability (ARV), and data‐driven latent trajectories. Mixed linear regression models for standardized composite cognitive scores were adjusted for: repeated measures, order of cognitive test, years from randomization, randomization arm, age, sex, race/ethnicity, years of education, CVD history, and APOE ε4.ResultFour HbA1c trajectories were identified: increasing, decreasing, stable‐high, and stable‐low. Composite cognitive scores were significantly lower for increasing, decreasing, and stable‐high HbA1c trajectories ‐compared to stable‐low HbA1c (Table). In multivariable analysis, higher baseline HbA1c, ARV, and VIM were associated with lower composite cognitive scores, and differences between groups were similar by years since randomization. Estimates for ARV and VIM were attenuated when adjusted for baseline HbA1c (not shown). Estimates were similar for tests from all cognitive domains, with little heterogeneity by randomization arm.ConclusionAmong individuals with T2D, higher HbA1c at baseline and greater HbA1c variability over 10 years were significantly associated with lower cognitive scores, suggesting that maintaining glucose control may be useful for the prevention of cognitive decline.

Nomogram analysis of the influencing factors of rapid renal decline in patients with biopsy-proven diabetic nephropathy in type 2 diabetes.

HbA1c variability may be related to risk of poor prognoses in chronic kidney disease patients with type 2 diabetes mellitus (T2DM). The aim of this study was to investigate whether HbA1c variability is associated with rapid renal function decline and the related risk factors in type 2 diabetic nephropathy (DN). An observational analysis was performed on 387 DN patients who were diagnosed by kidney biopsy from January 2006 through January 2016 at the Department of Nephrology, Jinling Hospital Affiliated to Nanjing University. The rapid decliners were defined as an estimated glomerular filtration rate (eGFR) decline slope ≥5 mL/min/1.73m2/year. HbA1c variability and 24 baseline clinicopathologic parameters was evaluated using the least absolute shrinkage and selection operator regression (LASSO) and multivariate logistic regression. The nomogram method was applied to score the factors, and a scoring model was constructed. HbA1c variability positively correlated with the rate of renal function decline (r=0.277; p<0.001). Higher baseline eGFR, lower serum calcium concentration, glomerular lesions, arteriosclerosis, and interstitial fibrosis and tubular atrophy (IFTA) were selected into the nomogram. The calibration curve for the probability of survival showed good agreement between the prediction by nomogram and actual observation. The C-index for predicting survival was 0.811 (95% confidence interval (CI) 0.680-0.785). The proposed nomogram and score provide a useful risk estimate of fast renal function decline in patients with type 2 diabetic nephropathy.

Long-term Visit-to-Visit Variability in Hemoglobin A1c and Kidney-Related Outcomes in Persons With Diabetes

To characterize associations between long-term visit-to-visit variability of hemoglobin A1c (HbA1c) and risk of adverse kidney outcomes in patients with diabetes. Observational study. 93,598 adults with diabetes undergoing routine care in Stockholm, Sweden. Categories of baseline and time-varying HbA1c variability score (HVS, the percentage of total HbA1c measures that vary by>0.5% [5.5mmol/mol] during a 3-year window): 0-20%, 21%-40%, 41%-60%, 61%-80%, and 81%-100%, with 0-20% as the reference group. Chronic kidney disease (CKD) progression (composite of>50% estimated glomerular filtration rate [eGFR] decline and kidney failure), acute kidney disease (AKI by clinical diagnosis or transient creatinine elevations according to KDIGO criteria), and worsening of albuminuria. Multivariable Cox proportional hazards regression. Compared with persons showing low HbA1c variability (HVS 0-20%), any increase in variability was associated with a higher risk of adverse kidney outcomes beyond mean HbA1c. For example, for patients with a baseline HbA1c variability of 81%-100%, the adjusted HR was 1.6 (95% CI, 1.47-1.74) for CKD progression, 1.23 [1.16-1.3] for AKI, and 1.28 [1.21-1.36] for worsening of albuminuria. The results were consistent across subgroups (diabetes subtypes, baseline eGFR, or albuminuria categories), in time-varying analyses and in sensitivity analyses including time-weighted average HbA1c or alternative metrics of variability. Observational study, limitations of claims data, lack of information on diet, body mass index, medication changes, and diabetes duration. Higher long-term visit-to-visit HbA1c variability is consistently associated with the risks of CKD progression, AKI, and worsening of albuminuria. The evidence for current guideline recommendations derives from clinical trials that focus on a single HbA1c as the definitive measure of efficacy of an intervention. However, long-term visit-to-visit fluctuations of HbA1c may provide additional value in the prediction of future kidney complications. We evaluated the long-term fluctuations in glycemic control in almost 100,000 persons with diabetes undergoing routine care in Stockholm, Sweden. We observed that higher long-term HbA1c fluctuation is consistently associated with the risks of chronic kidney disease progression, worsening of albuminuria and acute kidney injury. This finding supports a role for long-term glycemic variability in the development of kidney complications and illustrates the potential usefulness of this metric for risk stratification at the bedside beyond a single HbA1c test.

Relative contributions of fasting and postprandial glucose increments, glycemic variability, and non-glycemic factors to HbA1c in individuals with type 1 diabetes.

Evidence for contribution of basal and postprandial glucose increment, and glycemic variability to glycated hemoglobin (HbA1c) among adults with type 1 diabetes (T1D) is limited. This study aimed to capture glycemic fluctuation patterns and quantify contributions of these factors to HbA1c levels among adults with T1D. HbA1c, continuous glucose monitoring (CGM), and diet diaries were collected and pooled from two clinical trials. Available data sets were divided into HbA1c quartiles: group 1 (≤6.7%), group 2 (6.7%-7.3%), group 3 (7.3%-7.8%), and group 4 (≥7.8%). Area under curve above 110 mg/dL (AUC>110mg/dL ) in 24-h profile was defined as overall hyperglycemia and stratified with postprandial hyperglycemia (PHG, AUC>110mg/dL in 3-h period after meals) and basal hyperglycemia (BHG, AUC>110mg/dL in remaining period). Linear regression analysis was used to estimate the proportion of variance in HbA1c explained by BHG, preprandial glucose, PHG, glycemic variability, and non-glycemic factors (age, body mass index, hemoglobin, and duration). A total of 169 550 glucose data in 2409 meals recorded from 102 patients (male/female, 34/68) were included. Age and duration were 35.2 ± 12.6 and 8.9 (2.9, 13.0) years, with 51.0% using pumps. Overall, BHG was four times higher than PHG (p all <.05) and between-group comparisons showed BHG exhibited a progressive increase (group 1 vs. 2, 3, 4, p = .053, .086, .006) with fasting contribution of 76.1%, 82.6%, 81.5%, and 84.3% from group 1 to 4. The increment was not significant among groups 2, 3, and 4 (p > .05). Factors included in analysis explained a total of 74% of the variance in HbA1c, in which BHGaccounted for 32.1% of variance whereas PHG accounted for 24.4%. In group with HbA1c >7.3%, BHG accounted for a higher percentage with 33.8% of the variance in HbA1c. In our study, basal hyperglycemia better predicts overall glycemic control than postprandial hyperglycemia among adults with T1D. The relative contribution of basal hyperglycemia increased gradually with HbA1c increasing and predominant strategy for insulin titration among T1D is different among different levels of glycemic control.

Cover Image

The outside front cover image is based on the Original Article Effects of finerenone in people with chronic kidney disease and type 2 diabetes are independent of HbA1c at baseline, HbA1c variability, diabetes duration and insulin use at baseline by Janet B. McGill MD et al., https://doi.org/10.1111/dom.14999. Image Credit: Bayer.

Racial Residential Segregation and the Health of Black Youth With Type 1 Diabetes.

Black youth with type 1 diabetes (T1D) are at heightened risk for suboptimal glycemic control. Studies of neighborhood effects on the health of youth with T1D are limited. The current study investigated the effects of racial residential segregation on the diabetes health of young Black adolescents with T1D. A total of 148 participants were recruited from 7 pediatric diabetes clinics in 2 US cities. Racial residential segregation (RRS) was calculated at the census block group level based on US Census data. Diabetes management was measured via self-report questionnaire. Hemoglobin A1c (HbA1c) information was gathered from participants during home-based data collection. Hierarchical linear regression was used to test the effects of RRS while controlling for family income, youth age, insulin delivery method (insulin pump versus syringe therapy), and neighborhood adversity. HbA1c was significantly associated with RRS in bivariate analyses, whereas youth-reported diabetes management was not. In hierarchical regression analyses, whereas family income, age, and insulin delivery method were all significantly associated with HbA1c in model 1, only RRS, age, and insulin delivery method were significantly associated with HbA1c in model 2. Model 2 explained 25% of the variance in HbA1c (P = .001). RRS was associated with glycemic control in a sample of Black youth with T1D and accounted for variance in HbA1c even after controlling for adverse neighborhood conditions. Policies to reduce residential segregation, along with improved screening for neighborhood-level risk, hold the potential to improve the health of a vulnerable population of youth.

Higher glucose fluctuation is associated with a higher risk of cardiovascular disease: Insights from pooled results among patients with diabetes.

The relationship between glucose fluctuation and the risk of cardiovascular disease (CVD) in patients with diabetes remains elusive. Glycated hemoglobin (HbA1c) variability is a key parameter of glucose fluctuation. PubMed, Cochrane Library, Web of Science, and Embase were searched up to 1 July 2022. Studies reporting associations of HbA1c variability (HbA1c-SD), coefficient of variation of HbA1c (HbA1c-CV), and HbA1c variability score [HVS] with the risk of CVD among patients with diabetes were included. We used three different insights (a high-low value meta-analysis, a study-specific meta-analysis, and a non-linear dose-response meta-analysis) to explore the relationship between HbA1c variability and CVD risk. A subgroup analysis was also performed to screen the potential confounding factors. A total of 14 studies with 254 017 patients with diabetes were eligible. The highest HbA1c variability was significantly associated with increased risks of CVD (HbA1c-SD, risk ratio [RR] 1.45; HbA1c-CV, RR 1.74; HVS, RR 2.46; all p < .001) compared to the lowest HbA1c variability. The RRs of CVD for per HbA1c variability were significantly >1 (all p < .001). The subgroup analysis for per HbA1c-SD found a significant exposure-covariate interaction in the types of diabetes (p = .003 for interaction). The dose-response analysis showed a positive association between HbA1c-CV and CVD risk (P for nonlinearity <.001). Our study suggests that the higher glucose fluctuation is significantly associated with the higher CVD risk in diabetes patients based on HbA1c variability. The CVD risk associated with per HbA1c-SD might be higher among patients type 1 diabetes than patients with type 2 diabetes.

Decreased plasma iron levels in women with hyperglycemia are associated with inflammatory status and involve increased HbA1c, osmotic stability, and volume variability of red blood cells

Iron deficiency tendency in individuals with hyperglycemia influences the HbA1c levels' ability to estimate the stationary blood glucose levels. This study investigated the associations of iron status indicators and HbA1c levels with anthropometric, inflammatory, regulatory, metabolic, and hematologic variables in women with hyperglycemia to most widely characterize this iron deficiency tendency. A total of 143 volunteers (68 with normoglycemia and 75 with hyperglycemia) participated in this cross-sectional study. Mann-Whitney test was used to compare groups, and the search for associations between pairs of variables used the Spearman correlation method. In women with hyperglycemia, decreased plasma iron level is associated directly with increased HbA1c (p<0.001), and these changes are both related to C-reactive protein elevation (p=0.02 and p<0.05, respectively) and involve decreased mean hemoglobin concentration (p<0.01 and p<0.01), which in turn, involves enhanced osmotic stability (dX) (p<0.05) and volume variability (RDW) (p<0.0001) of erythrocytes, as well as decreased indirect bilirubin/total bilirubin ratio (p=0.04). This indirect bilirubin/total bilirubin decrease, which expresses decreased hemoglobin catabolism, does not seem to be solely a process associated with diminished intracellular concentrations of this protein (p=0.04) since it is associated with CRP elevation (p=0.03) and reduced LDL cholesterol (p<0.0001). In women with hyperglycemia, decreased plasma iron levels were associated with inflammatory status and involved increased HbA1c, osmotic stability, and volume variability of red blood cells.

The relationship between uric acid variability and cardiovascular risk factors in patients with diabetes

Aim: This study aimed to evaluate the relationship between uric acid variability and cardiovascular risk factors, primarily albuminuria and blood lipids, in patients with diabetes.&#x0D; Material and Method: Data from 174 patients with diabetes whose biochemical parameters were examined at least once a year were collected over the course of five years of regular follow-up. The five-year averages and standard deviations of each parameter for each person were calculated. The adjusted standard deviation for each parameter was considered as a measure of individual variability. The patients were divided into two groups according to the median of the mean uric acid and the median of the adjusted standard deviation of uric acid.&#x0D; Results: Between low and high uric acid variability groups, while there was no statistically significant difference for the mean values of following parameters, there was a difference in the variability of glucose (p=0.010), HbA1c (p=0.016), total cholesterol (p=0.008), and low-density lipoprotein-cholesterol (p=0.002). Moreover, there was difference in mean albuminuria (p= 0.019), albuminuria variability (p=0.040), mean triglyceride (p=0.011), triglyceride variability (p=0.018), and mean high-density lipoprotein-cholesterol cholesterol (p=0.008).&#x0D; Conclusion: Clinicians should pay attention to uric acid variability in addition to basal uric acid levels since it is associated with albuminuria, an atherogenic lipid profile, renal functions, and the variability of these parameters, independent of HbA1c and glucose levels.

The Impact of a Lockdown for the COVID-19 Pandemic on Seasonal HbA1c Variation in Patients with Type 2 Diabetes.

Glycemic control in patients with type 2 diabetes may be disrupted due to restricted medical service access and lifestyle changes during COVID-19 lockdown period. This retrospective cohort study examined changes of HbA1c levels in adults with type 2 diabetes 12 weeks before and after May 19 in 2021, the date that COVID-19 lockdown began in Taiwan. The mean levels of HbA1c-after were significantly lower than HbA1c-before in 2019 (7.27 ± 1.27% vs 7.43 ± 1.38%, p < 0.001), 2020 (7.27 ± 1.28% vs 7.37 ± 1.34%, p < 0.001), and 2021 (7.03 ± 1.22% vs 7.17 ± 1.29%, p < 0.001). Considering the seasonal variation of HbA1c, ΔHbA1c values (HbA1c-after minus HbA1c-before) in 2020 (with sporadic COVID-19 cases and no lockdown) were not significantly different from 2021 (regression coefficient [95% CI] = 0.01% [-0.02%, 0.03%]), while seasonal HbA1c variation in 2019 (no COVID-19) was significantly more obvious than in 2021 (-0.05% [-0.07, -0.02%]). In conclusion, HbA1c level did not deteriorate after a lockdown measure during the COVID-19 pandemic in Taiwan. However, the absolute seasonal reduction in HbA1c was slightly less during the COVID-19 pandemic compared with the year without COVID-19.