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Primary care physicians are central to the care of people with diabetes. Through an in-depth case study, the SingHealth Duke-NUS Diabetes Centre shares how general practitioners can leverage on continuous glucose monitoring to achieve optimal glycaemic control for their patients.
Glucose monitoring is vital to achieving optimal glycaemia in diabetes care. Glucose monitoring has evolved over the last century from urine glucose measurement and self-monitored capillary glucose measurements to continuous glucose monitoring (CGM).
Haemoglobin A1c (HbA1c) remains an essential surrogate for glycaemia as it strongly correlates with long-term diabetes complications. HbA1c also has a strong correlation with 24-hour mean glucose. However, HbA1c does not predict the risk of hypoglycaemia or postprandial hyperglycaemia.
CGM has improved rapidly in terms of accuracy as well as the duration of wear. Most CGM devices available currently can be worn for seven to 14 days, and require twice daily calibration or are factory-calibrated.
Sensor accuracy is constantly improving, and sensor technology is moving towards not requiring calibration as a standard. A CGM provides a sensor glucose every five to 15 minutes, translating to 96 to 288 readings per 24 hours.
Through a comprehensive case study, this article will discuss the use of CGM in a person with type 2 diabetes.
John, a 55-year-old male banker, is under your care. He has had type 2 diabetes for 15 years, a myocardial infarction ten years ago treated with percutaneous coronary intervention, dyslipidaemia and fatty liver.
Since adding a sodium-glucose cotransporter-2 inhibitor (SGLT2i) two years ago, his HbA1c has improved from an average of 10% to 8.5%. His latest HbA1c is 8.7%.
He weighs 72 kg with a BMI of 27 kg/m2. He takes 26 units of U100 glargine, linagliptin 5 mg, dapagliflozin 10 mg and gliclazide MR 120 mg, all once in the morning, and metformin 1000 mg twice daily. His estimated glomerular filtration rate (eGFR) is 63 ml/min/1.73 m2.
How would you further intensify John’s therapy to achieve optimal glycaemia?
John’s oral medications are at maximal / near maximal doses. His glargine dose of 26 units is 0.36 u/kg/day and could be increased further if there is persistent fasting hyperglycaemia.
What does an HbA1c of 8.7% tell you about John’s current glycaemia?
The HbA1c of 8.7% suggests that John’s 24-hour mean glucose is 12.5 mmol/L (mean glucose [mmol/L] = A1c x 2.32 - 7.68, using the updated glucose management indicator (GMI) equation). However, the HbA1c does not give you any information about his fasting glycaemia, hypoglycaemia or postprandial hyperglycaemia.
John is not keen to do more intensive capillary glucose monitoring, and in discussion with him, you decide to use a CGM to understand his glycaemia better.
TIME IN RANGES
What it is
Time in range (TIR) is the recommended glucose metric to quickly analyse a large amount of CGM data. TIR is the percentage of glucose readings between 3.9 and 10 mmol/L. A target of > 70% is recommended, which correlates to a HbA1c of < 7%.
Equally important is time below range (TBR) (level 1: < 3.9-3.0 mmol/L, level 2: < 3.0 mmol/L). Time below range is the sum of level 1 and level 2.
The recommended target for TBR is < 4%. Additionally, a stricter target of <1% is recommended for level 2 TBR (< 3 mmol/L).
John’s TIR is only 49% (target > 70%), his TBR is 0% and he has significant time above range (TAR) (> 10 mmol/L, 16 + 35 = 51%).
Time in ranges lets you immediately understand the major glycaemic issue from a CGM download. For John, it is hyperglycaemia. He does not have any hypoglycaemia.
However, time in ranges alone does not tell whether John’s fasting glycaemia is optimal, neither does it tell the periods of the day when he has hyperglycaemia. For this, we look at the ambulatory glucose profile.
AMBULATORY GLUCOSE PROFILE
The ambulatory glucose profile (AGP) is a 24-hour glucose overlay graph that summarises glucose data collected throughout the sensor wear period, depicting the distribution of glucose in different periods.
The x-axis denotes the time, and y-axis the glucose levels. The bold central line indicates the median glucose level, while the dark and light blue shaded areas represent the 25th to 75th and 5th to 95th percentile distribution of glucose, respectively.
AGP helps to identify the periods in a day when significant hypoglycaemia or hyperglycaemia occurs.
John’s overnight glucose level is within target and steady with no hypoglycaemia. However, he has significant postprandial hyperglycaemia during the day. His fasting glycaemia is in target; hence, no further increase of his basal insulin dose is necessary.
John is not surprised at his higher glucose levels in the daytime. At your advice, he has previously tried to limit his daytime meal portions but reports extreme hunger resulting in him reverting to his usual dietary habits.
You start glucagon-like-peptide-1 receptor agonist (GLP1-RA) injections after stopping linagliptin to target the predominant postprandial hyperglycaemia.
There is a significant improvement in TIR from 49% pre-GLP1-RA to 78%. However, the level 1 TBR is now 4%. John does not report any symptomatic hypoglycaemia but reports waking up with a bad headache on some days. Does John have nocturnal hypoglycaemia?
The AGP shows that John has episodes of nocturnal hypoglycaemia between 4am and 6am. Significant improvement in postprandial hyperglycaemia is also evident.
You recommend a reduction of the dose of U100 glargine from 26 to 20 units to avoid nocturnal hypoglycaemia.
DAILY GLUCOSE CURVES
Daily glucose curves are a valuable educational tool for going through diabetes self-care behaviours.
The graph shows that John had an episode of hypoglycaemia around 7.30am, followed by a rapid rise in glucose to about 16 mmol/L.
Hypoglycaemia should be treated with 15 g of quick-acting glucose (e.g. half a glass of fruit juice, three teaspoons of sugar or two to three pieces of jelly sweets). Overtreatment of hypoglycaemia can result in post-treatment hyperglycaemia.
John returns with a HbA1c of 7.8%. He now weighs 66 kg and has self-reduced his U100 glargine dose to 14 units based on his fasting glucose.
John was advised to monitor his fasting glucose for a few days every week and reduce his basal insulin dose by 10% (approximately 2 units) each time he developed recurrent fasting glucose readings < 4 mmol/L.
John’s TIR is 77% with a TBR of 2%, well within the recommended target of < 4%.
John’s AGP depicts much better glycaemia with minimal hypoglycaemia and much better postprandial hyperglycaemia. He does have post-breakfast hyperglycaemia, which could be improved further.
HbA1c alone does not provide a complete picture of a person’s glycaemia.
HbA1c does not provide information on the extent of hypoglycaemia, postprandial hyperglycaemia or glucose variability.
Continuous glucose monitoring (CGM) provides a detailed view of a person’s glycaemia and is a valuable complement to HbA1c.
Time in ranges provides a quick overview of a large amount of CGM data and identifies the major glycaemic issue. A time in range of > 70% correlates to an HbA1c of < 7%. A time below range of < 4% is recommended.
The ambulatory glucose profile helps to identify the specific periods of the day dysglycaemia is occurring. It also helps to match the diabetes therapy to the glycaemic patterns observed.
Daily glucose curves are a valuable tool to identify suboptimal diabetes self-care behaviours and educate people with diabetes.
When intensive insulin therapy is required
Insulin-deficient type 2 diabetes
All people with type 1 diabetes
Post pancreatectomy diabetes
For technology-assisted optimisation of diabetes care
Insulin pump therapy
For patients with obesity and diabetes
Obesity resistant to initial lifestyle and therapeutic interventions
Tadej Battelino et al. Clinical Targets for Continuous Glucose Monitoring Data Interpretation: Recommendations From the International Consensus on Time in Range. Diabetes Care 2019
American Diabetes Association. Diabetes Technology: Standards of Medical Care in Diabetes 2022. Diabetes Care 2022
S Rama Chandran et al. Beyond HbA1c: Comparing Glycemic Variability and Glycemic Indices in Predicting hypoglycaemia in type 1 and type 2 diabetes. Diabetes Technol Ther 2018
Bergenstal RM et al. Glucose management indicator (GMI): A new term for estimating A1c from continuous glucose monitoring. Diabetes Care 2018
Dr Suresh Rama Chandran is a Consultant with the Department of Endocrinology at Singapore General Hospital (SGH). He graduated with honours in MBBS, 2004 at the Jawaharlal Institute of Postgraduate Medical Education and Research, India; completed his post-graduate internal medicine training in 2009; and obtained MRCP, United Kingdom in 2010.
He completed his specialist training in diabetes and endocrinology at SGH in 2016. He completed a one-year clinical research fellowship at the King’s College Hospital, London, focusing on the holistic care of people with type 1 diabetes, and the use of technology to improve outcomes for people with type 1 diabetes while reducing the burden of self-care.
His research interests are in the optimal use of continuous glucose monitoring and the integration of technology into the daily lives of people with diabetes to improve their care.
Dr Daphne Gardner is a Senior Consultant with the Department of Endocrinology in Singapore General Hospital (SGH). She graduated from Oxford University, United Kingdom (UK) and was a clinical lecturer in Plymouth, UK before attaining specialist accreditation in endocrinology in Singapore. Her fellowship year was spent in the Oxford Centre for Diabetes, Endocrinology and Metabolism, UK.
Dr Gardner is the lead clinician for the Young Adults with Diabetes and Intensive Insulin therapy programme at SGH. She is on the physician faculty for the SingHealth Endocrinology Senior Residency Programme and is the Director of Education at the SingHealth Duke-NUS Diabetes Centre.
She has held two grants aimed at stratifying diabetes to direct personalised therapy and is the lead investigator for GLiMPSE (Glucose Monitoring Programme Singapore) which aims to use flash glucose monitoring and structured education to advance diabetes outcomes.
GPs can call the SingHealth Duke-NUS Diabetes Centre for appointments at the following hotlines:
Singapore General Hospital: 6326 6060Changi General Hospital: 6788 3003Sengkang General Hospital: 6930 6000KK Women’s and Children’s Hospital: 6692 2984Singapore National Eye Centre: 6322 9399