Toward Defining the Threshold Between Low and High Glucose Variability in Diabetes

Monnier, L.; Colette, C; Wojtusciszyn, Anne; Dejager, S.; Renard, Éric; Molinari, Nicolas; Owens, David R.

doi:10.2337/dc16-1769

Cited by 295 publications

(261 citation statements)

References 38 publications

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“…By CGM analysis with a large number of participants, we have shown here that the duration of hypoglycemia was inversely correlated with HbA 1c level in patients with type 2 diabetes treated with sulfonylureas. Whereas previous CGM‐based studies with smaller numbers of participants showed that hypoglycemia occurs more frequently in individuals treated with sulfonylureas than in those not taking these drugs, the relationship between HbA 1c level and the duration of hypoglycemia was not analyzed in these studies. A meta‐analysis found that the incidence of hypoglycemia was inversely correlated with baseline HbA 1c level in type 2 diabetes patients who initiated medications, including sulfonylureas, with the development of hypoglycemia being detected by symptoms or self‐monitoring of blood glucose, which does not allow quantitative assessment.…”

Section: Discussionmentioning

confidence: 98%

Relationship between glycated hemoglobin level and duration of hypoglycemia in type 2 diabetes patients treated with sulfonylureas: A multicenter cross‐sectional study

Matsuoka

Hirota

Takeda

et al. 2019

J of Diabetes Invest

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Aims/Introduction Sulfonylurea‐related hypoglycemia increases the risk of cardiovascular sequela, such as cardiac arrhythmia. This study aimed to clarify the relationship between the level of glycated hemoglobin (HbA1c) and the duration of hypoglycemia in type 2 diabetes patients treated with sulfonylureas. Materials and Methods Glucose levels in the enrolled patients (n = 300) were investigated with a professional continuous glucose monitoring device in the outpatient setting at six diabetes centers in Japan. Results A total of 269 participants completed the study. The duration of hypoglycemia with glucose values of <54 mg/dL was significantly longer in patients with an HbA1c level of ≤6.4% than in those with an HbA1c level of ≥8.0%, and that of hypoglycemia with glucose values of <70 mg/dL was significantly longer in patients with an HbA1c level of ≤6.4%, 6.5–6.9% or 7.0–7.4% than in those with an HbA1c level of ≥8.0%. Patients with an HbA1c level of ≤6.4% were exposed to glucose values of <70 mg/dL for >10% of the time in daily life (6.8 ± 5.6 min/h). The duration of hypoglycemia with glucose values of <70 mg/dL was longer at night than during the daytime, and the nadir of glucose values occurred between 03.00 and 05.00 hours irrespective of HbA1c level. The duration of hypoglycemia was associated with the duration of diabetes and sulfonylurea dose. Conclusions The duration of hypoglycemia was inversely correlated with HbA1c level and was longer during the night‐time than daytime in type 2 diabetes patients treated with sulfonylureas.

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Section: Discussionmentioning

confidence: 98%

Relationship between glycated hemoglobin level and duration of hypoglycemia in type 2 diabetes patients treated with sulfonylureas: A multicenter cross‐sectional study

Matsuoka

Hirota

Takeda

et al. 2019

J of Diabetes Invest

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“…We previously reported the association of glycaemic fluctuations, as detected by CGM, with hypoglycaemia in patients with T2D . Glycaemic fluctuations increase the risk of hypoglycaemia, regardless of the treatment used, including oral hypoglycaemic agents and insulin . Night‐time glycaemic fluctuations are also known to affect the quality of sleep, indicating that prevention of such fluctuations may lead to improved sleep quality and quality of life for patients with diabetes.…”

Section: Discussionmentioning

confidence: 99%

Addition of canagliflozin to insulin improves glycaemic control and reduces insulin dose in patients with type 2 diabetes mellitus: A randomized controlled trial

Torimoto

Okada

Goshima

et al. 2019

Diabetes Obesity Metabolism

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The aim of this study was to evaluate the efficacy of canagliflozin in reducing the required insulin dose and the risk of hypoglycaemia in type 2 diabetes (T2D). This study was conducted in patients with T2D treated with insulin. They were randomly assigned to the control (n = 17) and canagliflozin (n = 17, plus 100 mg/day canagliflozin) groups. In both groups, a defined insulin dose adjustment protocol was applied to achieve the same level of glycaemic control. The change from baseline in daily insulin dose was significantly smaller in the canagliflozin group (3.9 units/day) than in the control group (13.4 units/day; P = 0.040). Low blood glucose index and predicted % of blood glucose (BG) <70 mg/dL, which are hypoglycaemia-related variables, worsened significantly in the control group but both remained unchanged in the canagliflozin group. The standard deviation for night-time BG levels improved significantly only in the canagliflozin group. Supplementation of insulin therapy with 100 mg canagliflozin in patients with T2D reduced the required insulin dose and hypoglycaemic risk and flattened night-time glycaemic fluctuations while maintaining the same level of glycaemic control. K E Y W O R D Scanagliflozin, continuous glucose monitoring, hypoglycaemia, insulin therapy, type 2 diabetes

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“…An international consensus of expert opinion concluded that the CoV should become the primary measure of GV, with SD as a key secondary measure . Stable glucose levels were defined as a CoV under 36%, and unstable glucose levels were defined as a CoV of at least 36% . This provides a metric against which glucose data can be assessed and clinical intervention can be judged.…”

Section: Definition Of Glycaemic Variabilitymentioning

confidence: 99%

“…A recent study demonstrated that, in individuals without diabetes, mean GV measured by coefficient of variation (CoV) during the day and during the night was 17% ± 3% and 13% ± 4%, respectively, with a median of 96% of time spent between 70 and 140 mg/dL (3.9‐7.8 mmol/L) . Data concerning individuals with T1DM suggest that even those patients with so‐called “good variability” demonstrate a CoV of approximately 37%, which is more than twice that of individuals without diabetes …”

Section: Introductionmentioning

confidence: 99%

Glycaemic variability: The under‐recognized therapeutic target in type 1 diabetes care

Wilmot

Choudhary

Leelarathna

et al. 2019

Diabetes Obesity Metabolism

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Type 1 diabetes mellitus (T1DM) remains one of the most challenging long‐term conditions to manage. Despite robust evidence to demonstrate that near normoglycaemia minimizes, but does not completely eliminate, the risk of complications, its achievement has proved almost impossible in a real‐world setting. HbA1c to date has been used as the gold standard marker of glucose control and has been shown to reflect directly the risk of diabetes complications. However, it has been recognized that HbA1c is a crude marker of glucose control. Continuous glucose monitoring (CGM) provides the ability to measure and observe inter‐ and intraday glycaemic variability (GV), a more meaningful measure of glycaemic control, more relevant to daily living for those with T1DM. This paper reviews the relationship between GV and hypoglycaemia, and micro‐ and macrovascular complications. It also explores the impact on GV of CGM, insulin pumps, closed‐loop technologies, and newer insulins and adjunctive therapies. Looking to the future, there is an argument that GV should become a key determinant of therapeutic success. Further studies are required to investigate the pathological and psychological benefits of reducing GV.

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Toward Defining the Threshold Between Low and High Glucose Variability in Diabetes

Abstract: A %CV of 36% appears to be a suitable threshold to distinguish between stable and unstable glycemia in diabetes because beyond this limit, the frequency of hypoglycemia is significantly increased, especially in insulin-treated subjects.

Cited by 295 publications

References 38 publications

Relationship between glycated hemoglobin level and duration of hypoglycemia in type 2 diabetes patients treated with sulfonylureas: A multicenter cross‐sectional study

Relationship between glycated hemoglobin level and duration of hypoglycemia in type 2 diabetes patients treated with sulfonylureas: A multicenter cross‐sectional study

Addition of canagliflozin to insulin improves glycaemic control and reduces insulin dose in patients with type 2 diabetes mellitus: A randomized controlled trial

Glycaemic variability: The under‐recognized therapeutic target in type 1 diabetes care

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