Hypoglycemia Risk and Glucose Variability Indices Derived from Routine Self-Monitoring of Blood Glucose Are Related to Laboratory Measures of Insulin Sensitivity and Epinephrine Counterregulation

Abstract

Background: The widely held assumptions that in type 1 diabetes glucose variability may correlate with insulin sensitivity and impaired epinephrine counterregulation have not been studied directly. Here we investigate possible relationships between outpatient measures of glucose variability and risk for hypoglycemia with physiological characteristics: insulin sensitivity and hypoglycemia counterregulation. Methods: Thirty-four subjects with type 1 diabetes (14 women, 20 men; 37 AE 2.1 years old; glycosylated hemoglobin [HbA1c], 7.6 AE 0.21%) performed self-monitoring of blood glucose (SMBG) for a month, followed by an inpatient hyperinsulinemic euglycemic and hypoglycemic clamp. SMBG field data were used to calculate measures of glucose variability and risk of hypoglycemia, while the clamp procedure was used to evaluate insulin sensitivity and epinephrine response during induced hypoglycemia. Spearman partial correlations adjusted for age, duration of diabetes, body mass index, gender, and HbA1c were used to assess the relationship between the field indices of glucose variability and the physiological characteristics of diabetes. Results: Two glucose variability measures correlated positively (P < 0.01) with insulin sensitivity: the Average Daily Risk Range (ADRR) (r ¼ 0.5) and the Glycemic Lability Index (r ¼ 0.48). The Low Blood Glucose Index, a measure of the risk for hypoglycemia, and the ADRR correlated negatively with maximum epinephrine response during hypoglycemia: r ¼ À0.46, P < 0.01 and r ¼ À0.4, P ¼ 0.03, respectively. Conclusions: Higher insulin sensitivity and lower epinephrine response during hypoglycemia are related to increased glucose variability (as quantified by the ADRR), irrespective of HbA1c and other patient characteristics. Lower epinephrine relates to risk for hypoglycemia as well.

Are Risk Indices Derived From CGM Interchangeable With SMBG-Based Indices?

“…Based on these cutoff values, 3 risk zones, that is, HBGI < 4.5, HBGI between 4.5 and 9, and HBGI > 9, were identified to classify the subjects' risk of hyperglycemia from SMBG data points. 3 Given the capability of LBGI and HBGI of assessing the glycemic condition of a patient, their evaluation in the quantification of glucose variability (GV) was largely exploited in the literature, [4][5][6][7][8][9][10][11][12][13][14][15][16] replacing less sensitive markers such as mean and standard deviation (SD). 4,5 LBGI and HBGI were used to characterize the different GV of subjects with type 1 diabetes mellitus (T1DM) as compared to type 2 diabetes patients 6 , within the artificial pancreas to assess the performance of the control algorithm in terms of GV-related risk 7 , and, as computed on 1-hour segments of continuous glucose monitoring (CGM) profiles, to provide graphic representations of the evolution of the risk of hypo-and hyperglycemia as a function of the time of the day 8 .…”

“…Based on a structured theory of risk analysis of BG data presented in Kovatchev et al 3 , performance of glycemic control was widely assessed using LBGI/HBGI 9,10 , and 2 diabetes-specific computational algorithms were designed to predict probability of future hypoglycemic events and HbA1c levels [11][12][13][14] , which established LBGI and HBGI as necessary mediators in the algorithmic evaluation of risk of SH and metabolic control. If combined within the average daily risk range (ADRR) metric, 15 LBGI and HBGI were also shown to relate to insulin sensitivity and epinephrine counterregulation after hypoglycemia, 16 with an increased GV as quantified by ADRR occurring with higher insulin sensitivity and lower epinephrine response.…”

Glycaemic variability in diabetes: a tool for assessing the quality of glycaemic control and the risk of complications

“…Диагностика, контроль и лечение одним их лучших в оценке качества контроля гликемии благодаря высокой чувствительности и прогностической ценности [11][12][13]. Кроме того, ADRR представляет собой основу для выделения категорий пациентов с разным ри-ском лабильности гликемии [14].…”

“…Как показало моделирование гипогликемии в условиях гиперинсулинемического клэмпа, у больных СД1 параме-тры ВГ (показатели ADRR, LBGI), определенные по ре-зультатам самоконтроля глюкозы крови в течение месяца, отрицательно коррелируют с выраженностью адренало-вого ответа на гипогликемию [13]. Известно, что ответ надпочечников и вегетативной нервной системы на гипо-гликемию может снижаться при любом типе СД.…”

“…Аналогично, перенесенная накануне гипогликемия у больных СД2 приводит к запаздыванию выброса глюкагона, катехола-минов и к уменьшению выраженности адренергических и нейрогликопенических симптомов во время гипогли-кемии на следующий день: недавняя предшествующая ги-погликемия приводит не только к нарушению в системе контррегуляции, но и к нераспознаванию гипогликемий. Установлено, что повышенная чувствительность к ин-сулину, повышенный риск гипогликемии и сниженный адреналовый ответ на гипогликемию, измеряемый био-химически, связаны с увеличенной ВГ (ADRR, LI, LBGI) независимо от уровня НbA 1c [45]. Описанными особенно-стями можно объяснить тот факт, что приступы тяжелой гипогликемии у больных СД1 чаще происходят в пери-оды повышенной ВГ, которые можно ретроспективно на-блюдать по данным самоконтроля.…”