Glycaemic Variability in Diabetes

Introduction

Glycaemic variability (GV) is characterized by fluctuations in blood glucose levels, encompassing variations throughout the day, including instances of hypoglycaemia, postprandial elevations, and changes observed on different days.^1-4 The assessment of glycaemic control in clinical practice is significantly influenced by Glycaemic Variability. Studies on GV play a crucial role in enabling healthcare providers to recognize glucose level patterns, establish patient goals, monitor advancements, and assess the risk of long-term complications in diabetes. Growing evidence indicates a link between glycaemic variability and the onset of long-term complications in diabetes. Notably, there is a substantial decrease in the risk of long-term complications for each 10% increase in the time spent within the time in range (TIR).^5-8 Certain interventions in clinical practice, such as continuous glucose monitoring (CGM), medications, dietary adjustments, and exercise training, have the potential to enhance Glycaemic Variability. The use of CGM devices has significantly enhanced the evaluation of GV in clinical settings, providing a valuable metric to consider when assessing glycaemic control.^9-13 It is important to note that GV goals should be individualised based on the patient's needs and preferences and overall health status.

Complications of Glycaemic Variations

Glycaemic variability is significant as it can contribute to the development of both short-term and long-term complications associated with diabetes. Some key terminologies about glycaemic variability in diabetes are as noted below.

1. Hypoglycaemia: Significant fluctuations in blood glucose levels can result in occurrences of hypoglycaemia, characterized by low blood sugar levels. Symptoms of hypoglycaemia include shakiness, dizziness, confusion, and, in severe instances, loss of consciousness. Prompt treatment is essential for managing hypoglycaemia, as it is a serious condition. 
2. Hyperglycaemia: Glycaemic variability can result in elevated blood sugar levels, leading to hyperglycaemia. Prolonged periods of heightened blood sugar levels increase the risk of experiencing complications associated with diabetes, such as heart disease, kidney dysfunction, nerve damage, and visual disturbances.
3. Glucose Control: Glycaemic variability makes it difficult to achieve and maintain optimal glucose control. Fluctuating blood sugar levels can make it difficult to determine appropriate dosage of medication and insulin requirements.
4. Quality of Life: The unpredictable nature of glycaemic variability can negatively impact the quality of life in patients with diabetes. Constant monitoring, adjustments in the dosage of medication and the fear of hypoglycaemia can be stressful. The fear of hypoglycaemia causes greater stress and disrupts normal life.

Discussion

Clinical guidelines to detect glycaemic variations

Guidelines for detecting glycaemic variations in individuals with type 2 diabetes mellitus suggest using HbA1c as a diagnostic tool when fasting plasma glucose levels range between 100 and 125 mg/dL. The recommended frequency of HbA1c testing is contingent on the specific clinical circumstances, the treatment protocol in use, and the discretion of the healthcare provider.² Measurement every three months helps in the determination of achievement and maintenance of glycaemic targets by the patient. A 14- day CGM assessment of TIR and glucose management indicator (GMI) can be a surrogate for HbA1c in clinical management.² Presently, there is no unanimous agreement on the metrics for evaluating glycaemic variability. However, capillary blood glucose testing through self-monitored blood glucose (SMBG) and continuous glucose monitoring (CGM) stand as valuable tools for assessing GV. These tools aid clinicians and patients in addressing the limitations of HbA1c in diabetes management. It is noteworthy that the frequency of hypoglycaemic events in individuals with type 2 diabetes treated with insulin or oral antidiabetic agents has shown a notable increase when GV surpasses the mean standard deviation (SD) value.³

Glycaemic variability refers to the swings noted in blood glucose levels, including episodes of hypoglycaemia and postprandial hyperglycaemia.¹ It is an essential clinical practice to consider while assessing glycaemic control.² Real-time continuous glucose monitoring (RT-CGM) provides information on GV, time in range (TIR), and guidance to avoid hypoglycaemia, complementing HbA1c for diabetes management.³ TIR is the percentage of time per day within the target glucose range (3.9- 10.0 mmol/L).² It is a new parameter to evaluate blood glucose control in patients with diabetes.⁴ Studies have shown that GV and TIR are independently associated with chronic and acute complications encountered in diabetes.³ Hence, while managing diabetes, GV and increasing TIR are essential. The TIR initiative promotes the utilization of TIR data from continuous glucose monitors (CGMs) by patients and clinicians to guide treatment and lifestyle choices, aiming to enhance health outcomes.⁵ The patients can use CGM devices to monitor blood glucose levels in real-time. The dose of insulin has to be adjusted based on CGM data to maintain glucose levels within the target range. It is necessary to adapt a healthy diet and undertake regular exercise to facilitate regulation of blood glucose levels. One should avoid skipping meals or taking insulin doses at the wrong time. They have to work with a healthcare provider to develop an individualised diabetes management plan. Management of GV and increasing TIR are essential for diabetes management. CGM devices can provide valuable information to help patients and healthcare providers in adjusting the insulin dose and lifestyle changes to improve glycaemic control.

Medications or therapies that target glycaemic variability in diabetes

Basal insulin therapy effectively reduces fasting plasma glucose (FPG) and pre-prandial blood glucose levels.^1,2

Glucagon-related peptide-1-based therapy: This is a modern diabetes management modality that can help reduce GV.

Newer insulins: These are modern diabetes management modalities that can help to reduce GV.

Modern insulin pumps: These aids help in improving glucose control and minimize the risk of glucose extremes and severe hypoglycaemia.

Continuous glucose monitors (CGMs): These monitors play a crucial role in enhancing glycemic management and reducing the chances of extreme glucose levels and severe hypoglycemia. CGMs offer real-time glucose readings, aiding both patients and healthcare providers in recognizing patterns of glucose variability (GV). Key CGM metrics include time within the glycemic target range (70-180 mg/dL), time above the range (>180 mg/ dL), time below the hypoglycemic range (<70 mg/dL and <54 mg/dL), and GV represented by the coefficient of variation (CV).¹⁵

It is crucial to emphasize that the preferred treatment for GV should be customized according to the individual patient's specific requirements, preferences, and overall health condition.¹⁵

Time-in-range used in diabetes management

Time in range is a recently introduced metric in diabetes management, indicating the proportion of time during which blood glucose levels remain within a predefined range for individuals with diabetes. It is measured as a percentage of total hours in the day someone's blood sugar stays between 70-180 mg/dL, but the goal range can vary. TIR provides a more accurate picture of blood glucose over a period of time and is recommended to maintain a blood glucose range of 70 mg/dL (low) - 180 mg/dL (high) at least 70% of the time. TIR has emerged as a valuable metric for blood glucose, offering insights 'beyond HbA1c' and providing a deeper understanding of glycemic control in individuals with diabetes. TIR is related to diabetes management as it provides additional insights beyond HbA1c. It offers insight into the duration individuals experience elevated or reduced glucose levels during the day, detects daily fluctuations in blood sugar, and enables individuals to gauge the time spent within the optimal, feel-good range. Research findings indicate that both GV and TIR are independently linked to chronic and acute complications in diabetes. Hence, managing GV and increasing TIR are essential for diabetes management. The TIR initiative promotes the utilization of TIR data obtained from continuous glucose monitors by both patients and clinicians for making informed decisions regarding treatment and lifestyle adjustments, aiming to enhance overall health outcomes. In the realm of diabetes management, patients can leverage TIR data from CGMs to fine-tune insulin dosages and implement lifestyle modifications, fostering better glycemic control. Additionally, adhering to a nutritious diet, engaging in regular exercise, and avoiding the omission or mistiming of meals and insulin doses are essential practices for improved diabetes management. It is necessary to work with a diabetologist to develop an individualised diabetes management plan. While TIR is a potent tool for enhancing diabetes management, it should not be the sole metric employed. To overcome hurdles for the use of CGM, sustained efforts are required. It is anticipated that CGM measurements, particularly TIR, will be increasingly adopted in clinical practice.¹⁶

Summary

GV data can provide healthcare providers valuable insights to improve patient care. They can tailor treatment plans by identifying glucose level patterns for each individual’s needs. Patients can adjust medication or insulin dosages to maintain a balanced range, leading to better outcomes. The dosage of the medication or of insulin can be altered with the improvement of glycaemic control. Thus, the providers can offer personalised care.

Conflict of Interest

None

Financial support

Nil