HbA1c Coefficient Of Variation Research Articles

Serum Metabolomics Reveals a Potential Benefit of Methionine in Type 1 Diabetes Patients with Poor Glycemic Control and High Glycemic Variability.

Glycemic variability (GV) in some patients with type 1 diabetes (T1D) remains heterogeneous despite comparable clinical indicators, and whether other factors are involved is yet unknown. Metabolites in the serum indicate a broad effect of GV on cellular metabolism and therefore are more likely to indicate metabolic dysregulation associated with T1D. To compare the metabolomic profiles between high GV (GV-H, coefficient of variation (CV) of glucose ≥ 36%) and low GV (GV-L, CV < 36%) groups and to identify potential GV biomarkers, metabolomics profiling was carried out on serum samples from 17 patients with high GV, 16 matched (for age, sex, body mass index (BMI), diabetes duration, insulin dose, glycated hemoglobin (HbA1c), fasting, and 2 h postprandial C-peptide) patients with low GV (exploratory set), and another 21 (GV-H/GV-L: 11/10) matched patients (validation set). Subsequently, 25 metabolites were significantly enriched in seven Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways between the GV-H and GV-L groups in the exploratory set. Only the differences in spermidine, L-methionine, and trehalose remained significant after validation. The area under the curve of these three metabolites combined in distinguishing GV-H from GV-L was 0.952 and 0.918 in the exploratory and validation sets, respectively. L-methionine was significantly inversely related to HbA1c and glucose CV, while spermidine was significantly positively associated with glucose CV. Differences in trehalose were not as reliable as those in spermidine and L-methionine because of the relatively low amounts of trehalose and the inconsistent fold change sizes in the exploratory and validation sets. Our findings suggest that metabolomic disturbances may impact the GV of T1D. Additional in vitro and in vivo mechanistic studies are required to elucidate the relationship between spermidine and L-methionine levels and GV in T1D patients with different geographical and nutritional backgrounds.

Joint effect of visit-to-visit variability in LDL-cholesterol, HDL-cholesterol and HbA1c on cardiovascular and total mortality in patients with diabetes

BackgroundWe aimed to investigate the joint effect of visit-to-visit variability (VVV) in low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides and glycosylated hemoglobin (HbA1c) on cardiovascular mortality and total mortality in patients with diabetes.MethodsAmong 5194 participants with type 2 diabetes enrolled in the ACCORD lipid trial, VVVs of LDL-C, triglycerides, HDL-C, and HbA1c were assessed from baseline to 2 years of follow-up and expressed as coefficient of variation (CV). The study outcomes included cardiovascular mortality and all-cause mortality.ResultsOver a median follow-up of 3.0 years from the end of variability measurements at years 2, there were 305 (5.9%) cases of all-cause mortality, of which, 144 were cardiovascular causes. The positive relations between LDL-C CV and cardiovascular mortality were significantly stronger among participants with higher HDL-C CV (P for interaction = 0.023), and higher HbA1c CV (P for interaction = 0.015). However, there were no significant interactions between LDL-C CV and triglycerides CV (P for interaction = 0.591). Similar trends were found for all-cause mortality. Consistently, there were graded trends in the risk of mortality with the increasing numbers of higher CV of the three variables: LDL-C, HbA1c, and HDL-C (P for trend = 0.008 for cardiovascular mortality, and P for trend < 0.001 for all-cause mortality).ConclusionVVVs in LDL-C, HDL-C, and HbA1c may jointly affect the risks of cardiovascular and all-cause mortality in diabetes patients. Those with higher CVs of all three variables had the highest risks of cardiovascular and all-cause mortality.

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.

The Effect of HbA1c Variability as a Risk Measure for Microangiopathy in Type 1 Diabetes Mellitus.

Background: To measure the relationship between variability in HbA1c and microalbuminuria (MA) and diabetic retinopathy (DR) in the long term. Methods: A prospective case-series study, was conducted on 366 Type 1 Diabetes Mellitus patients with normoalbuminuria and without diabetic retinopathy at inclusion. The cohort was followed for a period of 12 years. The Cox survival analysis was used for the multivariate statistical study. The effect of variability in microangiopathy (retinopathy and nephropathy) was evaluated by calculating the standard deviation of HbA1c (SD-HbA1c), the coefficient of variation of HbA1c (CV-HbA1c), average real variability (ARV-HbA1c) and variability irrespective of the mean (VIM-HbA1c) adjusted for the other known variables. Results: A total of 106 patients developed diabetic retinopathy (29%) and 73 microalbuminuria (19.9%). Overt diabetic nephropathy, by our definition, affected only five patients (1.36%). Statistical results show that the current age, mean HbA1c, SD-HbA1c and ARV-HbA1c are significant in the development of diabetic retinopathy. Microalbuminuria was significant for current age, mean HbA1c, CV-HbA1c and ARV-HbA1c. Conclusions: By measuring the variability in HbA1c, we can use SD-HbA1c and ARV-HbA1c as possible targets for judging which patients are at risk of developing DR and MA, and CV-HbA1c as the target for severe DR.

Long-term HbA1c variability and the development and progression of diabetic retinopathy in subjects with type 2 diabetes

This study aimed to investigate whether long-term HbA1c variability is associated with the development and progression of diabetic retinopathy (DR) in subjects with type 2 diabetes. We retrospectively reviewed 434 type 2 diabetes subjects without DR who underwent regular DR screening. We reviewed fundus findings, collected HbA1c levels, and calculated the coefficient of variation (CV) and average real variability (ARV) of each subject’s HbA1c level. DR was developed in 55 subjects and progressed to moderate nonproliferative DR or worse DR in 23 subjects. On Cox proportional hazards regression analysis, HbA1c ARV, but not HbA1c CV, was significantly associated with DR development. However, the association between HbA1c variability and the DR progression rate to moderate nonproliferative DR or worse DR was not significant. The inter-visit HbA1c difference value on consecutive examination predicted DR development well and more careful screening for DR is needed for those with an absolute value change of 2.05%, an absolute increase of 1.75%, and an absolute decrease of 1.45% in HbA1c levels on consecutive examination. These results indicate that long-term glucose variability measured by HbA1c ARV might be an independent risk factor for DR development in addition to the mean HbA1c level in early diabetic subjects.

Association between visit-to-visit HbA1c variability and the risk of cardiovascular disease in patients with type 2 diabetes.

To investigate the association between visit-to-visit HbA1c variability and the risk of cardiovascular disease in patients with type 2 diabetes. We performed a retrospective cohort study of 29 260 patients with at least four HbA1c measurements obtained within 2 years of their first diagnosis of type 2 diabetes. Different HbA1c variability markers were calculated, including the standard deviation (SD), coefficient of variation (CV) and adjusted SD. Cox proportional hazards regression models were used to estimate the association of these HbA1c variability markers with incident cardiovascular disease. During a mean follow-up of 4.18 years, a total of 3746 incident cardiovascular disease cases were diagnosed. Multivariate-adjusted hazard ratios for cardiovascular disease across the first, second, third and fourth quartiles of HbA1c SD values were 1.00, 1.30 (95% confidence interval [CI] 1.18-1.42), 1.40 (95% CI 1.26-1.55) and 1.59 (95% CI 1.41-1.77) (P for trend <.001), respectively. When we utilized HbA1c CV and adjusted HbA1c SD values as exposures, similar positive associations were observed. HbA1c variability was also associated with the risk of first and recurrent severe hypoglycaemic events. A mediating effect of severe hypoglycaemia was observed between HbA1c variability and incident cardiovascular disease. Large visit-to-visit HbA1c variability is associated with an increased risk of cardiovascular disease in patients with type 2 diabetes. Severe hypoglycaemia may mediate the association between HbA1c variability and incident cardiovascular disease.

Visit-to-visit HbA1c variability is associated with in-stent restenosis in patients with type 2 diabetes after percutaneous coronary intervention

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

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

To investigate whether long-term glycemic variability (GV) is associated with vascular complication development in type 2 diabetes. 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. 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). Long-term GV was associated with increased risk of vascular outcomes in type 2 diabetes.

Prognostic Significance of Long-term HbA1c Variability for All-Cause Mortality in the ACCORD Trial.

The association between high glycemic variability and all-cause mortality has been widely investigated in epidemiological studies but rarely validated in glucose-lowering clinical trials. We aimed to identify the prognostic significance of visit-to-visit HbA1c variability in treated patients in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial population. We studied the risk of all-cause mortality in relation to long-term visit-to-visit HbA1c variability, expressed as coefficient of variation (CV), variability independent of the mean (VIM), and average real variability (ARV), from the 8th month to the transition from intensive to standard glycemic therapy. Multivariable Cox proportional hazards models were used to estimate adjusted hazard ratio (HR) and 95% CI. Compared with the standard therapy group (n = 4,728), the intensive therapy group (n = 4,755) had significantly lower mean HbA1c (6.6% [49 mmol/mol] vs. 7.7% [61 mmol/mol], P < 0.0001) and lower CV, VIM, and ARV (P < 0.0001). In multivariate adjusted analysis, all three HbA1c variability indices were significantly associated with total mortality in all patients as well as in the standard- and intensive-therapy groups analyzed separately. The hazard ratios for a 1-SD increase in HbA1c variability indices for all-cause mortality were 1.19 and 1.23 in intensive and standard therapy, respectively. Cross-tabulation analysis showed the third tertile of HbA1c mean and VIM had significantly higher all-cause mortality (HR 2.05; 95% CI 1.17-3.61; P < 0.01) only in the intensive-therapy group. Long-term visit-to-visit HbA1c variability was a strong predictor of all-cause mortality. HbA1c VIM combined with HbA1c mean conferred an increased risk for all-cause mortality in the intensive-therapy group.

Effect of mean HbA1c on the association of HbA1c variability and all-cause mortality in patients with type 2 diabetes.

To evaluate the effect of mean HbA1c on the correlation between HbA1c variability and all-cause mortality, and the risks associated with different levels of HbA1c and glycaemic control status in patients with type 2 diabetes. Patients with type 2 diabetes and at least three HbA1c measurements within 12-24 months were included. HbA1c variability score, coefficient of variation (CV) and standard deviation (SD) were used to evaluate variability. A variability score of 50 was set as a cutoff to define low and high variability. A total of 4216 patients were included, of whom 1196 died during the observation period (11.1 ± 3.2 years). All-cause mortality increased with HbA1c variability score and the quartiles of HbA1c CV and SD. The strength of this association was attenuated after adjustment for mean HbA1c, and the risks associated with HbA1c variability and glycaemic control status were similar. The highest associated risk was observed with an HbA1c variability score of >50 and mean HbA1c of ≥7.5%. Mortality risk was significantly higher with a mean HbA1c of ≤6.0% and >8.5% and of ≤6.0% and >8.0% for low and high HbA1c variability, respectively. Mean HbA1c contributed to the correlation between HbA1c variability and all-cause mortality. The risks associated with HbA1c variability and glycaemic control status were similar. The relationship between mean HbA1c and mortality presented a J-shaped distribution for both low and high HbA1c variability.

Living alone is associated with visit-to-visit HbA1c variability in men but not in women in people with type 2 diabetes: KAMOGAWA-DM cohort study.

The purpose of this study was to evaluate the association between living alone and glycemic parameters, especially glycemic variability, in men and women with type 2 diabetes. Lifestyle factors, including living alone, were assessed by a questionnaire in this cross-sectional study. Average, standard deviation (SD), and coefficient of variation (CV) of HbA1c were calculated using the values of HbA1c, which were extracted from the medical record for 1 year. Eighteen percent of men (35/198) and 17% of women (18/103) were living alone. In men, the average of HbA1c (59.9 mmol/mol [11.0] vs. 55.7 mmol/mol [9.1], 7.6% [1.0] vs. 7.2% [0.8], p = 0.018), and CV of HbA1c (0.06 [0.03-0.08] vs. 0.03 [0.02-0.05], p < 0.001) were all significantly higher in men who were living alone than in men who weren't. However, there were no differences in the average (53.2 mmol/mol [11.4] vs. 56.0 mmol/mol [8.8], 7.0% [1.0] vs. 7.3% [0.8], p = 0.252) or CV (0.03 [0.02-0.05] vs. 0.03 [0.02-0.04], p = 0.845) between women who were living alone and women who weren't. Multiple regression analyses revealed that living alone was associated with CV of HbA1c after adjusting for covariates in men (β = 0.180, p = 0.005), but not in women (β = 0.085, p = 0.369). We showed that living alone is associated with visit-to-visit HbA1c variability in men, but not women, with type 2 diabetes. In clinical practice, it is necessary to pay attention to glycemic control in men who are living alone.

Relationship between daily and visit-to-visit glycemic variability in patients with type 2 diabetes.

The aim of the study was to explore the relationship between daily glycemic variability (GV) and visit-to-visit glycemic variability (VVV) in patients with type 2 diabetes (T2DM). A total of 156 outpatients with T2DM who had undergone continuous glucose monitoring (CGM) for 5 days were included in this study. Indices of GV, i.e., standard deviation and coefficient of variation (CV) of glucose, mean amplitude of glycemic excursion (MAGE) and mean of the daily differences (MODD) were calculated from the CGM data. VVV was calculated as CV of HbA1c or glycated albumin (GA) from HbA1c or GA measured for 3 years. Relationships among clinical parameters, GV and VVV were evaluated. Age was positively, and BMI and C-peptide index were inversely correlated with GV such as CV glucose and MAGE, while BMI was positively correlated with VVV. Mean glucose rather than GV was correlated with VVV. In contrast, time in range (TIR, 70-180 mg/dL) was correlated with both mean HbA1c or GA and VVV. In conclusion, GV and VVV were differently correlated with clinical parameters and were hardly correlated with each other. TIR was correlated with both mean HbA1c and VVV, suggesting that efforts to achieve optimal TIR are practical strategies to reduce VVV in patients with T2DM.

HbA1c variability in adults with type 1 diabetes on continuous subcutaneous insulin infusion (CSII) therapy compared to multiple daily injection (MDI) treatment

ObjectiveTo determine if continuous subcutaneous insulin infusion (CSII) therapy is associated with lower glycatedhaemoglobin (HbA1c) variability (long-term glycaemic variability; GV) relative to multiple daily injection (MDI) treatment in adults with...

Skipping breakfast is associated with glycemic variability in patients with type 2 diabetes.

The association between skipping breakfast and glycemic parameters, including glycemic variability, in patients with type 2 diabetes is not well understood. Therefore, the aim of this study was to investigate the effects of skipping breakfast on glycemic parameters, including glycemic variability, in patients with type 2 diabetes. In this cross-sectional study, we assessed lifestyle factors, including skipping breakfast, using a questionnaire method. We calculated the average, SD, and coefficient of variation (CV) of hemoglobin (Hb)A1c levels. The CV of HbA1c was defined as follows: CV=(SD / average HbA1c)×100 (%). Among 317 patients, 22 (6.9%) skipped breakfast. Patients who did not eat breakfast were younger (58 [14.5] versus 67.4 [10.1] y, P < 0.001) than those who did. The proportion of current smokers among patients skipping breakfast was higher than the proportion of smokers among patients who did not (40.9 versus 11.5%, P < 0.001). Average (7.7 [1.3] versus 7.1 [0.8]%, P=0.003), SD (0.32 [0.17-0.85] versus 0.21 [0.14-0.35], P=0.024) and CV (0.04 [0.03-0.10] versus 0.03 [0.02-0.05], P=0.028) of HbA1c level were higher among patients who skipped breakfast than among those who did not. Multiple regression analysis revealed that skipping breakfast was associated with average HbA1c (β = 0.527, P=0.006) and CV of HbA1c (β=0.026, P=0.001) after adjusting for age, sex, body mass index, duration of diabetes, exercise, smoking, amount of alcohol consumption, total energy intake, carbohydrate intake, and medications for diabetes. Skipping breakfast is independently associated with poor glycemic control, including glycemic variability, in patients with type 2 diabetes.

1652-P: The Association between Long-Term HbA1c Variability, Blood Pressure, Cholesterol, and Body Weight in Type 2 Diabetes: Subanalysis of ABC Study

Aim: Visit-to-visit variability (VVV) of HbA1c was reported to be the risk of cardiovascular disease (CVD) in patients with type 2 diabetes mellitus (T2DM). However, factors related to VVV of HbA1c remain unclear. This study is first examined relationship between VVV of HbA1c and various parameters including VVV of blood pressure (BP), low-density lipoprotein-cholesterol (LDL-C), and body mass index (BMI). Material and Methods: Analyzed were 4,678 patients with T2DM throughout Japan (38 hospitals). The inclusion criteria were patients whose HbA1c, BP, LDL-C, and BMI were measured 12 or more times during the 24-month period. VVV of HbA1c, BP, LDL-C, and BMI were evaluated using the coefficient of variation (CV). This study is sub-analysis of ABC trial (UMIN000034231). Results: Mean age of participants was 61.3 ± 9.4 years (mean ± SD) and HbA1c was 57.2 ± 13.5 mmol/mol (7.4 ± 1.2%). Table shows univariate correlate and multiple regression analysis of HbA1c CV. HbA1c CV was correlated with HbA1c baseline, SBP CV, LDL-C CV, and BMI CV. In the multiple regression analysis, HbA1c baseline, LDL-C, and BMI CV were the strongest predictors of HbA1c CV. Conclusion: VVV of HbA1c was strongly correlated with VVV of LDL-C and BMI, and HbA1c baseline in patients with T2DM. A large-scale clinical trial needs to be conducted to clarify factors affecting VVV of HbA1c. Disclosure S. Minato: None. D. Matsutani: None. Y. Tsujimoto: None. Y. Kayama: None. M. Sakamoto: None. M. Nishikawa: None. K. Utsunomiya: None.

Prognostic impact of visit-to-visit glycemic variability on the risks of major adverse cardiovascular outcomes and hypoglycemia in patients with different glycemic control and type 2 diabetes.

The prognostic impact of visit-to-visit glycemic variability on clinical outcomes in patients with different glycemic control and type 2 diabetes remains obscure. We investigated glucose variability and clinical outcomes for patients in the groups of Good glycemic control (GC), Insufficient glycemic control (IC), and Poor glycemic control (PC) in a prospective cohort study. By using data from Action in Diabetes and Vascular disease: preterAx and diamicroN-MR Controlled Evaluation (ADVANCE), 930 patients were enrolled from 61 centers in China and grouped into GC, IC, and PC according to their glycated hemoglobin A1c (HbA1c) and fasting plasma glucose (FPG). Visit-to-visit glycemic variability was defined using the coefficient of variation (CV) of five measurements of HbA1c and FPG taken 3-24 months after treatment. Multivariable Cox proportional hazards models were employed to estimate adjusted hazard ratio (aHR). Among 930 patients in the intensive glucose control, 82, 538, and 310 patients were assigned to GC, IC, and PC, respectively. During the median of 4.8 years of follow-up, 322 patients were observed hypoglycemia and 244 patients experienced major adverse cardiovascular events (MACE). The CV of HbA1c and FPG was significantly lower for GC (6.0 ± 3.8, 11.2 ± 6.2) than IC (8.3 ± 5.6, 17.9 ± 10.6) and PC (9.5 ± 6.3, 19.3 ± 10.8). High glycemic variability was associated with a greater risk of MACE (aHR: 2.21; 95% confidence interval (CI): 1.61-3.03; p < 0.001) and hypoglycemia (aHR: 1.36; 95% CI: 1.04-1.79; p = 0.025) than low glycemic variability in total patients. The consistent trend was also found in subgroups of GC, IC, and PC. This prospective cohort study showed that glycemic variability was significantly lower for GC than IC and PC. Furthermore, glycemic variability was associated with the risk of MACE and hypoglycemia in total patients and subgroups of different glycemic control.

Visit-to-visit HbA1c variability is inversely related to baroreflex sensitivity independently of HbA1c value in type 2 diabetes

BackgroundThe relationship between long-term glycemic variability (GV) represented by visit-to-visit HbA1c variability and baroreflex sensitivity (BRS) in type 2 diabetes mellitus (T2DM) has not been clarified by previous literature. The present study is the first to examine the relationships between visit-to-visit HbA1c variability and BRS.MethodsThis retrospective study initially analyzed data on 94 patients with T2DM. Visit-to-visit HbA1c variability was evaluated using the intrapersonal coefficient of variation (CV), standard deviation (SD), and adjusted SD of 8 or more serial measurements of HbA1c during a 2-year period. The BRS was analyzed using the sequence method. Short-term GV was assessed by measuring the glucose CV during 24-h continuous glucose monitoring (CGM). The primary objective was to determine if there was a relationship between visit-to-visit HbA1c variability (HbA1c CV) and BRS. Secondary objectives were to examine the relationship between other variables and BRS and the respective and combined effects of long-term GV (HbA1c CV) and short-term GV (CGM CV) on BRS.ResultsA total of 57 patients (mean age 67.2 ± 7.7 years, mean HbA1c 7.3 ± 1.0%) who met this study’s inclusion criteria were finally analyzed. In the univariate analysis, HbA1c CV (r = − 0.354, p = 0.007), HbA1c SD (r = − 0.384, p = 0.003), and adjusted HbA1c SD (r = − 0.391, p = 0.003) were significantly related to low levels of BRS. Multiple regression analysis showed that HbA1c CV, HbA1c SD, and adjusted HbA1c SD were inversely related to BRS. Furthermore, although the increase in either long-term GV (HbA1c CV) or short-term GV (CGM CV) as determined by 24-h CGM was inversely correlated with BRS, additional reductions in BRS were not shown in participants with both HbA1c CV and CGM CV values above the median.ConclusionsVisit-to-visit HbA1c variability was inversely related to BRS independently of the mean HbA1c in patients with T2DM. Therefore, visit-to-visit HbA1c variability might be a marker of reduced BRS in T2DM.

HbA1c variability and diabetic peripheral neuropathy in type 2 diabetic patients

BackgroundDiabetic complications may be associated with impaired time-dependent glycemic control. Therefore, long-term glycemic variability, assessed by variations in haemoglobin A1c (HbA1c), may be a potential risk factor for microvascular complications, such as diabetic peripheral neuropathy (DPN). We investigated the association of HbA1c variability with DPN in patients with type 2 diabetes.MethodsIn this cross-sectional study, 563 type 2 diabetic patients who had been screened for DPN and undergone quarterly HbA1c measurements during the year preceding enrolment were recruited. DPN was confirmed in patients displaying both clinical manifestations of neuropathy and abnormalities in a nerve conduction evaluation. HbA1c variability was assessed by the coefficient of variation of HbA1c (CV-HbA1c), and the mean of HbA1c (M-HbA1c) was calculated. In addition, medical history and clinical data were collected.ResultsAmong the recruited patients, 18.1% (n = 102) were found to have DPN, and these patients also presented with a higher CV-HbA1c than the patients without DPN (p < 0.001). The proportion of patients with DPN increased significantly from 6.9% in the first to 19.1% in the second and 28.5% in the third tertile of CV-HbA1c (p for trend < 0.001). After adjusting for initial HbA1c, M-HbA1c and other clinical factors via multiple logistic regression analysis, the odds ratios (ORs) for DPN in the second and third versus those in the first CV-HbA1c tertile were 3.61 (95% CI 1.62–8.04) and 6.48 (2.86–14.72), respectively. The area under the receiver operating characteristic (ROC) curve of CV-HbA1c was larger than that of M-HbA1c, at 0.711 (95% CI 0.659–0.763) and 0.662 (0.604–0.721), respectively. ROC analysis also revealed that the optimal cutoff value of CV-HbA1c to indicate DPN was 15.15%, and its corresponding sensitivity and specificity were 66.67% and 65.73%, respectively.ConclusionsIncreased HbA1c variability is closely associated with DPN in type 2 diabetic patients and could be considered as a potent indicator for DPN in these patients.

Visit-to-visit HbA1c variability and systolic blood pressure (SBP) variability are significantly and additively associated with mortality in individuals with type 1 diabetes: An observational study.

To investigate the relationship between variability in both visit-to-visit HbA1c and SBP and mortality in individuals with type 1 diabetes. The Scottish Care Information (SCI) Diabetes dataset was used to identify 5952 individuals with type 1 diabetes for inclusion in this observational study. The SCI-Diabetes dataset allowed access to blood pressure values, HbA1c readings, demographic information and mortality rates for all study participants. Participants were dichotomized to above and below median values for both HbA1c coefficient of variation (CV) and SBP CV, thus dividing participants into 4 cohorts for survival analysis. Survival analysis was carried out over 1430 days. A Cox proportional hazard model was used to allow comparison of mortality between the 4 cohorts. Of the 5952 patients, death occurred in 416. CV for both HbA1c and SBP were significantly associated with mortality. The median values for HbA1c CV and SBP CV were 8.0 and 8.1, respectively. The hazard ratio for high HbA1c CV only (P = .0015) was 1.78 ± 0.36. The hazard ratio for high SBP CV only (P = .0018) was 1.69 ± 0.33. The hazard ratio for both high HbA1c CV and high SBP CV (P < .00001) was 2.37 ± 0.32. Our findings demonstrate that variability of both HbA1c and SBP is significantly and additively associated with mortality in individuals with type 1 diabetes. The variability of these parameters might be useful for risk stratification and is a potential target for future interventional studies.

HbA1c variability is associated with increased mortality and earlier hospital admission in people with Type 1 diabetes.

Despite evidence of morbidity, no evidence exists on the relationship between HbA1c variability and mortality in Type 1 diabetes. We performed an observational study to investigate whether the association between HbA1c variability and mortality exists in a population of people with Type 1 diabetes. As a secondary outcome, we compared onset of first hospital admission between groups. People with Type 1 diabetes were identified for inclusion from the Scottish Care Information - Diabetes data set. This database includes data of all people known to have diabetes who live within Scotland. A survival analysis was carried out over a 47-month period comparing two groups; group 1 with a HbA1c coefficient of variation (CV) above the median CV value, and group 2 with a CV below the median value. Time to death or first admission was also analysed. ACox proportional hazard model was used to compare time to death, adjusting for appropriate covariables. Some 6048 individuals with Type 1 diabetes were included in the analysis. Median HbA1c CV was 7.9. The hazard ratio (HR) for mortality for those with an HbA1c CV above the median value is 1.5 over 47months of follow-up (P<0.001). HR for survival to either the first admission to hospital or death for those with an HbA1c CV above the median value was 1.35 (95% confidence interval 1.25-1.45) over 730days of follow-up (P<0.001). Our results show that people with greater HbA1c variability have a higher rate of mortality and earlier hospital admission in Type 1 diabetes.