The relation between HbA1c variability and diabetic autonomic neuropathy among type-2 diabetic patients

Background: Diabetic autonomic neuropathy (DAN) is the most neglected major and widespread microvascular complication of type-2 diabetes mellitus, involving multiple body organs. DAN is a subtype of diabetic peripheral neuropathy.Objective: To investigate the relationship between the variability of HbA1c and diabetic autonomic neuropathy in type-2 diabetes patients.Materials and methods: This study recruited a total of 150 type-2 diabetic patients to screen for diabetic autonomic neuropathy and estimated quarterly levels of HbA1c were performed within the year before enrollment. With a noninvasive procedure, DAN was validated by careful history taking, anthropometric assessment, clinical manifestations and neurological assessment.Results: Out of 150 type- 2 diabetic patients, recruited randomly, where 81 were female and 69 were male. Among all patients 29 (19.33%) had been screened positive for DAN which showed higher HbA1c than non-DAN patients. Different autonomic neuropathic dysfunction among total diabetic patients were also studies and found that the highest prevalence of sexual dysfunction among all autonomic dysfunction prevalence which is 16.66% whereas the lowest prevalence was postural hypotension that is 6.66%. The second higher prevalence is urinary incontinence (10.66%). Abnormal sweating (9.33%) and nocturnal diarrheas (7.33%) are in third and fourth position respectively. No significant (p>0.05) differences were found in the case of BMI, sex, systolic, and diastolic blood pressure between DAN and non-DAN. Data shows a major (p<0.05) risk factor for DAN has also been the prolonged period of diabetes and older age.Conclusion: The study indicates that the increased level of HbA1c in type-2 diabetic patients is closely correlated with DAN and may be considered a potent predictor of DAN in the recruited patients.International Journal of Human and Health Sciences Vol. 06 No. 01 January’22 Page: 89-95

HbA1C variability among type 2 diabetic patients: a retrospective cohort study

Background Studies have found that HbA1C variability is an independent risk factor for diabetic complications in type 2 diabetic patients. This study aims to find factors contributing to higher HbA1C variability in the community. Methods The study was conducted in the southern district of Israel, in Clalit Health Services (CHS). The study population was type 2 diabetic individuals aged 40–70 years in 2005, with a follow-up period of 11 years, until 2015. The definition of HbA1C variability was done by the standard deviation from the average HbA1C value of the entire study period, which was calculated for each participant. The study population was divided into two groups, “variability group” with HbA1C SD > 1.2, and “comparison group” of participants with HbA1C SD ≤ 1.2. In the univariate analysis we used X2 or Fisher test for categorical variables and independent t-test for numeric continuous variables. In the multivariate analysis we used logistic regression as well as assessing for possible interactions. Statistical analysis was ascribed for p < 0.05. All the data was drawn from the computerized medical system used by all primary care physicians and nurses in CHS working in the community. Results The study population included 2866 participants, the average age was 58.6 years, 43.3% men and 56.7% women. Each participant had an average of 20.9 HbA1C measures in their computerized medical record during the 11 years of follow up. The mean HbA1C value was 7.8%. We found 632 patients (22%) with a high variability, whereas 2234 (78%) had a low variability of HbA1C. In the “variability group” there was a higher percentage of smokers, BMI ≥ 30 and a higher rate of visits to diabetic clinics compared to the “no variability” group. In the “variability group” we found a much higher use of insulin and ACE inhibitors. The highest frequency of variability was between HbA1c values of 8.1–8.5. The multivariate analysis showed that HbA1C variability was associated with insulin use (OR = 4.1, p < 0.001), with age (OR = 0.939, p < 0.001), and Ischemic heart disease (OR = 1.258, p = 0.03). BMI ≥ 30 was almost statistically significant (OR = 1.206, p = 0.063). Gender was statistically insignificant. Conclusions In conclusion, HbA1C variability might be used as an additional marker in Diabetes Mellitus type 2, reflecting the disease complexity characteristics and the patient’s lifestyle profile.

Hba1c Variability Has a Strong Relationship With Peripheral Sensory And Motor Neuropathy in Type-2 Diabetes Mellitus

Diabetic peripheral neuropathy (DPN) is one of the most common long-term microvascular complications of diabetes. This study was undertaken to investigate the association of HbA1c variability with diabetic peripheral neuropathy (sensory and motor) in patients with type-2 diabetes. In this cross-sectional study, a total of 150 type-2 diabetic patients were 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 neurological abnormalities assessment. Among the recruited patients, 24% (n = 36) were found to have DPN, and these patients also presented with a higher HbA1c as compared to the patients without DPN (p<0.05). In addition, the advanced age and longer duration of diabetes were important and significant (p<0.05) risk factors for peripheral neuropathy. Overall study suggests that increased HbA1c level is strongly associated with DPN (sensory and motor) in type-2 diabetic patients and could be considered as a potent indicator for DPN in the recruited patients. J. Bio-Sci. 29(1): 93-100, 2021 (June)

Relationship between glycemic intraday variations evaluated in continuous glucose monitoring and HbA1c variability in type 2 diabetes: pilot study

Background HbA1c variability is independent of mean HbA1c, and associated with mortality due to vascular complications. However, the significance of HbA1c variability is unknown at present. In this study, we used flash glucose monitoring (FGM) and evaluated glycemic intraday variations, and then examined the association with HbA1c variability. Methods We conducted a retrospective pilot study of 26 patients treated at the Outpatient department for type 2 diabetes mellitus (T2DM), and evaluated the following items associated with blood glucose levels and their changes/variations using FGM. The primary endpoint was factor(s) associated with standard deviation (SD) HbA1c over a 6-month period. To adjust for the effect of varying numbers of HbA1c measurements, we used the adjusted SD of HbA1c. Results There were significant correlations between mean HbA1c and each of glucose management indicator, maximum, percent time at glucose > 180 mg/day, mean of daily difference of blood glucose, and high blood glucose index. Adjusted SD HbA1c correlated significantly with percent time at glucose < 70 mg/dL and low blood glucose index. We estimated the regression coefficient of adjusted SD HbA1c using multivariate linear regression analysis, and noted that the presence of hypoglycemia affected Adjusted SD HbA1c (β = 0.130, SE = 0.044, P = 0.008). Hypoglycemia was noted in 17 patients, and adjusted SD HbA1c was significantly higher (p = 0.001) in the hypoglycemic group (0.22 ± 0.12%), compared with the non-hypoglycemic group (0.08 ± 0.05%). The cut-off value of adjusted SD HbA1c was 0.109% in the hypoglycemic group. Conclusions The results showed that HbA1c variability is associated with hypoglycemia. For patients with high HbA1c variability, we recommend evaluation for the presence of hypoglycemia and reconsideration of their treatment regimen including their glucose-lowering medications. Trial registration The study protocol and opt-out method of informed consent were approved by the ethics committees of the University of Occupational and Environmental Health (Trial registration: H27-186, Registered 25 Dec 2015)

Association of Mean and Variability of HbA1c with Heart Failure in Patients with Type 2 Diabetes

Heart failure (HF) is a common presentation in patients with type 2 diabetes mellitus (T2DM). Previous studies revealed that the HbA1c level is significantly associated with HF. However, little is known about the association between HbA1c variability and HF. We aimed to evaluate the association of mean and variability of HbA1c with HF in patients with T2DM. Using Diabetes Share Care Program data, patients with T2DM who had mean HbA1c (HbA1c-Mean), and HbA1c variability (tertiles of HbA1c-SD and HbA1c-adjSD) within 12–24 months during 2001–2008 were included. The cutoffs of HbA1c-Mean were set at <7%, 7–7.9%, and ≥8%. Hazard ratios (HRs) for HF during 2008–2018 were estimated using Cox proportional hazard models. A total of 3824 patients were included, of whom 315 patients developed HF during the observation period of 11.72 years. The associated risk of HF increased with tertiles of HbA1c variability and cutoffs of HbA1c-Mean. In mutually adjusted models, HbA1c-Mean showed a consistent dose-response association with HF, while the association of HbA1c variability with HF disappeared. Among patients with HbA1c-Mean <7%, the associated risk of HF in patients with HbA1c variability in tertile 3 was comparable to patients with HbA1c-Mean ≥8%. In conclusion, mean HbA1c was an independent predictor of HF and not explained by HbA1c variability. In addition to absolute HbA1c level, targeting on stability of HbA1c in patients with good glycemic control was also important for the development of HF in patients with T2DM.

Prediction of atrial fibrillation and sudden cardiac death in type 2 diabetic patients on insulin: a territory-wide observational cohort study

Funding Acknowledgements Type of funding sources: None. Introduction With the global shift towards a more personalized approach in the management of diabetes, there is an increasing interest in exploring the application of new parameters, such as HbA1c and lipid variability, to better monitor disease progression and evaluate the prognosis. Given that metabolic abnormalities may exacerbate the risk of adverse outcomes in patients with type 2 diabetes mellitus, patients who are partially or fully dependent on insulin are more likely to have severe disease and may be at higher risks of arrhythmias. Purpose The aim of the present study aims was to assess the predictive value of HbA1c and lipid variability towards ventricular tachycardia (VT), ventricular fibrillation (VF), or SCD, as well as incident AF in type 2 diabetic patients receiving insulin therapy. Methods The territory-wide retrospective observational study consists of type 2 diabetic patients prescribed with insulin, who attended publicly funded clinics and hospitals in Hong Kong between January 1st, 2009 to December 31st, 2009. Variability in total cholesterol, low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), triglyceride, and HbA1c were assessed through their standard deviation (SD) and coefficient of variation (CV) for patients with at least three measurements of the respective indices. Univariate and multivariate Cox regression analysis was used to predict for the primary outcomes- incident SCD and AF. Results A total of 23329 patients (mean ± SD age: 64 ± 14 years old; 51% male; mean HbA1c 8.6 ± 1.3%) were included. In total, 2512 and 1846 patients experienced incident SCD and AF respectively over the course of follow-up. On multivariate analysis, higher HbA1c variability (SD: hazard ratio [HR]: 1.45, 95% confidence interval [CI] 1.21-1.75; p &lt; 0.0001) and triglyceride variability (SD: HR: 1.36, 95%CI: 1.24-1.49; p &lt; 0.0001) were associated with increased of SCD risk. By contrast, only the increase in LDL-C variability was predictive of AF (SD: HR 2.95, 95%CI 1.37-6.39; p= 0.006). Conclusions Higher HbA1c variability and lipid variability were associated with increased of SCD risk while only higher LDL-C variability was predictive of incident AF. Therefore, poor glucose control and variability in lipid parameters in diabetic patients are associated with SCD and incident AF. These observations suggest the need to re-evaluate the extent of glycemic control required for outcome optimization.

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.