Prevent hypoglycaemia when using automated insulin delivery systems in type 1 diabetes requires near normal glycaemic variability.

Aim: Although newer technologies of insulin delivery in type 1 diabetes have facilitated an improvement in glycaemic control the risk of hypoglycaemia remains a threat. Therefore, it is important to define the thresholds of glycaemic variability below which the risk of hypoglycaemia can be eliminated or at least minimized.

Methods: Randomized controlled trials conducted from 2017 to 2023 comparing Sensor-Augmented-Pumps and Augmented Insulin Delivery Systems (n = 16 and 22 studies, respectively) were selected.

Glycaemic variabilities: Key questions in pursuit of clarity.

After years of intensive investigation, the definition of glycaemic variability remains unclear and the term variability in glucose homoeostasis might be more appropriate covering both short and long-term glycaemic variability. For the latter, we remain in the search of an accurate definition and related targets. Recent work leads us to consider that the within-subject variability of HbA1c calculated from consecutive determinations of HbA1c at regular time-intervals could be the most relevant index for assessing the long-term variability with a threshold value of 5% (%CV = SD of HbA1c/mean HbA1c) to separate stability from lability of HbA1c.

Glucose variability and diabetes complications: Risk factor or biomarker? Can we disentangle the "Gordian Knot"?

« Variability in glucose homoeostasis » is a better description than « glycaemic variability » as it encompasses two categories of dysglycaemic disorders: i) the short-term daily glucose fluctuations and ii) long-term weekly, monthly or quarterly changes in either HbA1c, fasting or postprandial plasma glucose. Presently, the relationship between the "variability in glucose homoeostasis" and diabetes complications has never been fully clarified because studies are either observational or limited to retrospective analysis of trials not primarily designed to address this issue. Despite the absence of definitive evidence from randomized controlled trials (RCTs), it is most likely that acute and long-term glucose homoeostasis "cycling", akin to weight and blood pressure "cycling" in obese and hypertensive individuals, are additional risk factors for diabetes complications in the presence of sustained ambient hyperglycaemia.

The obesity treatment dilemma: Why dieting is both the answer and the problem? A mechanistic overview.

Restricted-calorie diets are the most worldwide used treatments for obesity. Although such strategies are based on the first law of thermodynamics, the real life clinical practice demonstrates that the observed weight losses are divergent from those theoretically predicted. Loosely adherence to recommendations is one of the main causes for the limited efficacy of dieting, but many additional factors can be involved in the hurdles to weight loss.

Application of medium-term metrics for assessing glucose homoeostasis: Usefulness, strengths and weaknesses.

This review aims to address the issue of whether or not the newer metrics, developed for continuous glucose monitoring [real-time CGM (rtCGM), intermittently scanned CGM (isCGM)], enhance assessment of the "glucose tetrad": Ambient hyperglycaemia, short-term glycaemic variability, postprandial glucose excursions and hypoglycaemia. The ever-increasing number of metrics offered with rtCGM and isCGM includes intermediate-term indicators referred to as "time in range" (TIR), the time spent in the range of 70-180mg/dL (TIR 70-180); time spent above the range of 180mg/dL (TAR>180); and time spent below the range of 70mg/dL or 54mg/dL (TBR<70 or TBR<54). The former two values are strongly correlated with HbA1c levels and can therefore serve as short- or medium-term markers of ambient hyperglycaemia, depending on whether glucose sensors are worn over periods of several days or weeks, respectively, whereas the latter indices (TBR<70 or<54) are more relevant for capturing hypoglycaemic events and quantifying their magnitude and duration, in contrast to random spot testing with self-monitoring of blood glucose.

Review of methods for detecting glycemic disorders.

Prediabetes (intermediate hyperglycemia) consists of two abnormalities, impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) detected by a standardized 75-gram oral glucose tolerance test (OGTT). Individuals with isolated IGT or combined IFG and IGT have increased risk for developing type 2 diabetes (T2D) and cardiovascular disease (CVD). Diagnosing prediabetes early and accurately is critical in order to refer high-risk individuals for intensive lifestyle modification.

Respective Contributions of Glycemic Variability and Mean Daily Glucose as Predictors of Hypoglycemia in Type 1 Diabetes: Are They Equivalent?

Objective: To evaluate the respective contributions of short-term glycemic variability and mean daily glucose (MDG) concentration to the risk of hypoglycemia in type 1 diabetes.

Research Design And Methods: People with type 1 diabetes ( = 100) investigated at the University Hospital of Montpellier (France) underwent continuous glucose monitoring (CGM) on two consecutive days, providing a total of 200 24-h glycemic profiles. The following parameters were computed: MDG concentration, within-day glycemic variability (coefficient of variation for glucose [%CV]), and risk of hypoglycemia (presented as the percentage of time spent below three glycemic thresholds: 3.

Glucocentric risk factors for macrovascular complications in diabetes: Glucose 'legacy' and 'variability'-what we see, know and try to comprehend.

Recognizing the role of dysglycaemia, 'ambient' hyperglycaemia, 'metabolic memory' and glycaemic variability as risk factors for macrovascular diseases is mandatory for effective diabetes management. Chronic hyperglycaemia, also referred to as 'ambient hyperglycaemia', was only fully acknowledged as a risk factor for adverse cardiovascular events when the beneficial effects of intensive glucose-lowering strategies were consolidated in the extended follow-up (> 10 years) of patients included in the United Kingdom Prospective Diabetes Study (UKPDS) and Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) Study. These studies led to the concept of the glucose-lowering 'legacy effect' (metabolic memory), which depends on the duration and magnitude of glucose-lowering, and is not a 'forever' phenomenon, as demonstrated in the 15-year follow-up of the Veterans Affairs Diabetes Trial (VADT).

The application of simple metrics in the assessment of glycaemic variability.

The assessment of glycaemic variability (GV) remains a subject of debate with many indices proposed to represent either short- (acute glucose fluctuations) or long-term GV (variations of HbA). For the assessment of short-term within-day GV, the coefficient of variation for glucose (%CV) defined as the standard deviation adjusted on the 24-h mean glucose concentration is easy to perform and with a threshold of 36%, recently adopted by the international consensus on use of continuous glucose monitoring, separating stable from labile glycaemic states. More complex metrics such as the Low Blood Glucose Index (LBGI) or High Blood Glucose Index (HBGI) allow the risk of hypo or hyperglycaemic episodes, respectively to be assessed although in clinical practice its application is limited due to the need for more complex computation.

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

Objective: To define the threshold for excess glucose variability (GV), one of the main features of dysglycemia in diabetes.

Research Design And Methods: A total of 376 persons with diabetes investigated at the University Hospital of Montpellier (Montpellier, France) underwent continuous glucose monitoring. Participants with type 2 diabetes were divided into several groups-groups 1, 2a, 2b, and 3 ( = 82, 28, 65, and 79, respectively)-according to treatment: ) diet and/or insulin sensitizers alone; ) oral therapy including an insulinotropic agent, dipeptidyl peptidase 4 inhibitors (group 2a) or sulfonylureas (group 2b); or ) insulin.

Near normal HbA1c with stable glucose homeostasis: the ultimate target/aim of diabetes therapy.

Achieving near normal glucose homeostasis implies that all components of dysglycemia that are present in diabetes states be eliminated. Reducing ambient/overall hyperglycemia is a pre-requisite to eliminate the risk of development and progression of diabetes complications. More controversially however, are the relative and related contributions of postprandial glucose excursions, glucose variability, hypoglycemia and the dawn phenomenon across the spectrum of dysglycemia.

Postprandial and basal hyperglycaemia in type 2 diabetes: Contributions to overall glucose exposure and diabetic complications.

Both postprandial and fasting (basal) hyperglycaemia contribute to overall hyperglycaemia (ambient hyperglycaemia) in type 2 diabetes (T2D). Postprandial glucose is the main contributor in fairly well controlled individuals, whereas basal hyperglycaemia becomes the preponderant contributor in poorly controlled patients. A more generally acceptable description of the contribution of postprandial glucose is to simply say that the absolute impact of postprandial glucose to HbA1c remains constant at approximately 1% across the entire HbA1c spectrum of non-insulin-treated patients with T2D.

Ramadan and diabetes: What we see, learn and understand from continuous glucose monitoring.

Abstinence from eating and drinking from dawn to sunset characterizes the holy month of Ramadan. For the 50 million Muslims worldwide with diabetes who adhere to this religious fast, the practice results in marked changes in glucose homoeostasis. The sunset meal (Iftar) that breaks the fasting state is followed by exaggerated surges in blood glucose and sustained overnight hyperglycaemia in cases of nocturnal overfeeding.