Association of long-term visit-to-visit variability of HbA1c and fasting glycemia with hypoglycemia in type 2 diabetes mellitus

Abstract

BackgroundSelf-management of blood glucose levels to avoid hypoglycemia is vital for patients with type 2 diabetes mellitus (T2DM). The association between specific metrics of glycemic variability (glycosylated hemoglobin A1c [HbA1c] and fasting plasma glucose [FPG]) and severe hypoglycemia has not been fully studied in patients with T2DM.MethodsIn this post hoc analysis, patients with established T2DM with a high risk of cardiovascular disease were included in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study. The Cox proportional hazards model was used to investigate the relationship between glycemic variability and hypoglycemia requiring medical assistance (HMA) and hypoglycemia requiring any third-party assistance (HAA). The prognostic value of HbA1c/FPG variability for our predefined outcomes was compared using Harrell’s C method.ResultsAfter adjusting for confounders, each increase in HbA1c variability of 1 standard deviation (SD) indicated a higher risk of HAA (hazard ratio [HR]: 1.10; 95% confidence interval [CI]: 1.03–1.16; P < 0.01) and HMA events (HR: 1.11; 95% CI: 1.03–1.20; P < 0.01). Meanwhile, each increase in FPG variability of 1 SD increased the risk of HAA (HR: 1.40; 95% CI: 1.31–1.49; P < 0.01) and HMA events (HR: 1.46; 95% CI: 1.35–1.57; P < 0.01). Meanwhile, models, including FPG variability, had better prognostic value for our predefined outcomes than HbA1c variability (P < 0.01).ConclusionsIncreased visit-to-visit variability in HbA1c and fasting glycemia is associated with a greater risk of severe hypoglycemic events in T2DM patients. FPG variability is a more sensitive indicator than HbA1c variability.Trial registrationhttp://www.clinicaltrials.gov. Unique identifier: NCT00000620.

Depression is associated with heart failure in patients with type 2 diabetes mellitus

“…In contrast to previous studies, all participants in the ACCORD study had T2DM with CVD or a higher risk of CVD; thus, they had a higher risk of HF than previous studies ( 6 , 18 ). Therefore, our study might have had more power to detect an association between depressive symptoms and incidence of HF than previous studies.…”

“…Depression is also one of the most prevalent symptoms in patients with HF. Symptoms of depression worsen the quality of life and the prognosis of patients with established HF (6,7). However, it is unclear whether depression is a risk factor for HF or an incidental comorbidity of HF, due to different populations and instruments used to assess depressive symptoms (8)(9)(10)(11)(12).…”

Higher HbA1c variability is associated with increased arterial stiffness in individuals with type 1 diabetes

“…The sustained long-term effects of a past hyperglycaemic period, entailed in the concept of metabolic memory and possibly mediated through epigenetic changes [ 39 ], might require a longer period spent in hyperglycaemia than that captured by short-term GV, which would intriguingly explain the distinct role of long-term GV as a risk factor. On the other hand, HbA 1c variability has been associated with a greater risk of severe hypoglycaemic events in individuals with type 2 diabetes [ 40 ]. Hypoglycaemia itself is proposed as a cardiovascular risk factor, possibly through hemodynamic changes, arrhythmias, and a combination of oxidative stress, endothelial dysfunction, inflammation and thrombosis, which seem to further increase in response to rebound hyperglycaemia [ 14 , 41 – 43 ].…”

A study of factors influencing long-term glycemic variability in patients with type 2 diabetes: a structural equation modeling approach

“…These results suggest that the HbA 1C fluctuations observed in this study were relatively stable, and that lower HbA 1C variability in diabetic patients could potentially reduce or delay the occurrence of complications associated with diabetes ( 33 ). Moreover, lower levels of HbA 1C variability in patients could potentially reduce the number of hypoglycemic events, alleviate economic and psychological stress, and improve their quality of life ( 27 ).…”

“…Among diabetic patients, HbA 1c variability is a risk factor for mortality and death due to cardiovascular disease ( 22 , 23 ), and it is independent of HbA 1c levels ( 24 ). In addition, numerous observational and randomized clinical trial studies have demonstrated that HbA 1c variability is linked to the risk of both microvascular and macrovascular complications in diabetes patients, as well as increased occurrences of hypoglycemia ( 12 , 19 , 25 – 27 ). Furthermore, a meta-analysis revealed that HbA 1c variability is connected with the incidence of dementia among diabetic patients ( 28 ).…”