Utility of different glycemic control metrics for optimizing management of diabetes

Abstract

The benchmark for assessing quality of long-term glycemic control and adjustment of therapy is currently glycated hemoglobin (HbA1c). Despite its importance as an indicator for the development of diabetic complications, recent studies have revealed that this metric has some limitations; it conveys a rather complex message, which has to be taken into consideration for diabetes screening and treatment. On the basis of recent clinical trials, the relationship between HbA1c and cardiovascular outcomes in long-standing diabetes has been called into question. It becomes obvious that other surrogate and biomarkers are needed to better predict cardiovascular diabetes complications and assess efficiency of therapy. Glycated albumin, fructosamin, and 1,5-anhydroglucitol have received growing interest as alternative markers of glycemic control. In addition to measures of hyperglycemia, advanced glucose monitoring methods became available. An indispensible adjunct to HbA1c in routine diabetes care is self-monitoring of blood glucose. This monitoring method is now widely used, as it provides immediate feedback to patients on short-term changes, involving fasting, preprandial, and postprandial glucose levels. Beyond the traditional metrics, glycemic variability has been identified as a predictor of hypoglycemia, and it might also be implicated in the pathogenesis of vascular diabetes complications. Assessment of glycemic variability is thus important, but exact quantification requires frequently sampled glucose measurements. In order to optimize diabetes treatment, there is a need for both key metrics of glycemic control on a day-to-day basis and for more advanced, user-friendly monitoring methods. In addition to traditional discontinuous glucose testing, continuous glucose sensing has become a useful tool to reveal insufficient glycemic management. This new technology is particularly effective in patients with complicated diabetes and provides the opportunity to characterize glucose dynamics. Several continuous glucose monitoring (CGM) systems, which have shown usefulness in clinical practice, are presently on the market. They can broadly be divided into systems providing retrospective or real-time information on glucose patterns. The widespread clinical application of CGM is still hampered by the lack of generally accepted measures for assessment of glucose profiles and standardized reporting of glucose data. In this article, we will discuss advantages and limitations of various metrics for glycemic control as well as possibilities for evaluation of glucose data with the special focus on glycemic variability and application of CGM to improve individual diabetes management.

Keywords: Continuous glucose monitoring; Diabetes mellitus; Glucose dynamics; Glycemic variability; Hemoglobin A1c; Markers of glycemic control; Postprandial glucose; Risk of hyperglycemia and hypoglycemia; Standardization.

Figure 1

Relationship between hemoglobin A1c and mean glucose obtained from (A) continuous glucose monitoring and (B) self-monitoring of blood glucose in a cohort of 114 non-insulin treated type 2 diabetic patients. Medians (25^th-75^th percentile) for age, diabetes duration, and HbA1c were 59.0-68.0 yr, 2.0-10.0 yr, and 6.0%-7.3% (42-56 mmol/mol), respectively. The lines denote the regression lines (black), 95%CI (blue), and prediction intervals (red) (Kohnert et al, Unpublished data). CGM: Continuous glucose monitoring; HbA1c: Hemoglobin A1c.

Figure 2

Differentiation between treatment groups of type 2 diabetic patients using the average daily risk range scores. Sample size for each group is given in parenthesis. Between-treatment group differences were evaluated by one-way analysis of variance and are statistically significant (P < 0.001). MET: Metformin; SU: Sulfonylurea; OAD: Oral antidiabetic drugs; INS: Insulin (Kohnert et al, Unpublished data).

Figure 3

Continuous glucose monitoring traces from seven patients with an HbA1c value of 6.5% selected from the type 2 diabetes cohort treated with oral antidiabetes drugs. Average 24-h glucose profiles are shown. Shading indicates the glucose target range 3.9-10.0 mmol/L (modified from Kohnert et al, Bull Karaganda University 2013; 72: 6-15).

Figure 4

Glycemic Markers and Risk of Diabetic Complications. The solid lines show established relationships of the glycemic markers with microvascular and macrovascular diabetes complications; dotted lines represent possible relations with glycemic variability. FPG: Fasting plasma glucose; PPG: Postprandial plasma glucose; HbA1c: Hemoglobin A1c; GA: Glycated albumin; 1,5 AG: 1,5 Anhydroglucitol; SD: Standard deviation of plasma glucose values; MAGE: Mean amplitude of glycemic excursions; CV: Coefficient of variation; ADRR: Average daily risk range; GRADE: Glycemic risk assessment diabetes equation.