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.

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.

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.

"Mild dysglycemia" in type 2 diabetes: to be neglected or not?

"Mild dysglycemia" in type 2 diabetes can be defined by the range of HbA1c levels≥6.5% (48 mmol/mol) and<7% (53 mmol/mol), which corresponds to when the risk for vascular complications begins to increase. This "mild dysglycemia" is characterized by both a dawn phenomenon (a spontaneous blood glucose rise in the early morning) and an excess of post-prandial glucose excursions in the absence of abnormal elevation in basal glucose, especially during nocturnal periods.

Magnitude of the dawn phenomenon and its impact on the overall glucose exposure in type 2 diabetes: is this of concern?

Objective: To assess the magnitude of the dawn phenomenon and its impact on the total glucose exposure in type 2 diabetes.

Research Design And Methods: A total of 248 noninsulin-treated persons with type 2 diabetes who underwent continuous glucose monitoring were divided into three groups selected by treatments: diet alone (n = 53); insulin sensitizers alone (n = 82); and insulin secretagogues alone or in combination with insulin sensitizers (n = 113). The dawn phenomenon (∂ glucose, mg/dL) was quantified by its absolute increment from nocturnal nadir to prebreakfast value.

Frequency and severity of the dawn phenomenon in type 2 diabetes: relationship to age.

Objective: To know whether age has an independent effect on the dawn phenomenon in noninsulin-using type 2 diabetes.

Research Design And Methods: Eighty-one individuals with type 2 diabetes were matched for HbA(1c) and divided by age into three subgroups of 27 individuals (1: ≥70 years; 2: 60-69 years; and 3: ≤59 years). All underwent ambulatory continuous glucose monitoring for quantifying the dawn phenomenon (i.

Add-on therapies to metformin in type 2 diabetes: what modulates the respective decrements in postprandial and basal glucose?

Background: Oral hypoglycemic agents (OHAs) are usually divided into postprandial and basal drugs. As their actions are probably more complex, it is important to ascertain which factors can modulate their effects.

Subjects And Methods: Thirty-one type 2 diabetes patients treated with metformin (glycosylated hemoglobin [HbA1c] 6.

The glycemic triumvirate and diabetic complications: is the whole greater than the sum of its component parts?

The dysglycemia of diabetes mellitus can be depicted as the glycemic triumvirate with its 3 main components: the sustained chronic (ambient) hyperglycemia, glucose variability and hypoglycemic episodes. The respective contributions of these glycemic disorders to the overall risk for diabetic complications remain a subject of debate. At present, there is cogent evidence for the direct deleterious effect of ambient hyperglycemia while the roles exerted by glucose variability and hypoglycemia remain less documented and only based on observational and pathophysiological studies.

Postprandial and basal glucose in type 2 diabetes: assessment and respective impacts.

The independent contribution of postprandial glucose (PPG) excursions to the overall glucose exposure and its role in the development of both micro- and macrovascular complications of diabetes remain subject to continuing debate in type 2 diabetes. Discussion continues on whether postprandial hyperglycemia is the main contributor to the overall hyperglycemia in fairly well-controlled individuals, whereas basal hyperglycemia becomes the preponderant contributor in poorly controlled patients. The concern about the role of PPG as a risk factor for diabetes complications is related to the controversial data obtained in individuals with impaired glucose tolerance.

The contribution of glucose variability to asymptomatic hypoglycemia in persons with type 2 diabetes.

Background: The present study was designed to define the relative contributions of glucose variability and ambient glycemia to the incidence of asymptomatic hypoglycemia in type 2 diabetes.

Methods: Two hundred twenty-two persons with type 2 diabetes were divided into three groups: Group I (n = 53) on insulin sensitizers alone, Group II (n = 87) on oral hypoglycemic agents (OHAs) to include at least one insulin secretagogue, and Group III (n = 82) on insulin alone or in combination with OHAs. Ambient mean glucose concentration (MG) values (in mmol/L) and glycemic variability (SD around the mean glucose value) (in mmol/L) or mean amplitude of glycemic excursions (in mmol/L) were assessed by a continuous glucose monitoring system.

Insulin therapy has a complex relationship with measure of oxidative stress in type 2 diabetes: a case for further study.

Background: Because pharmacotherapies in type 2 diabetes exert complex effects, we examined the different anti-diabetic strategies, especially the influence of insulin doses, on the activation of oxidative stress, a key player in atherosclerosis, ageing and the risk of cancer.

Methods: This observational study included 122 persons with type 2 diabetes, 61 treated with oral hypoglycaemic agents alone (group I), 61 treated with a combination of oral hypoglycaemic agents and insulin at either a low dose (<0.40 unit/kg/day, group IIa, n = 30) or high dose (≥0.