Glycemic variability predicts inflammation in adolescents with type 1 diabetes

Abstract

Background Adolescents with type 1 diabetes (T1D) have increased risk of cardiovascular disease as well as elevations in biomarkers of systemic inflammation, plasma protein oxidation and vascular endothelial injury. It is unclear whether hyperglycemia itself, or variations in blood glucose are predictors of these abnormalities. Methods This study was designed to determine the relationship of inflammatory (C-reactive protein, CRP), oxidative (total anti-oxidative capacity, TAOC) and endothelial injury (soluble intracellular adhesion molecule 1, sICAM1) markers to glycemic control measures from 3 days of continuous glucose monitoring (CGM) and to hemoglobin A1c (HbA1c), and HbA1c × duration area under the curve (A1cDur). Results Seventeen adolescents (8 F/9M; age, 13.1 ± 1.6 years (mean±SD); duration, 4.8 ± 3.8 years, BMI, 20.3 ± 3.1 kg/m2; A1c, 8.3 ± 1.2%) were studied. Log CRP but was not related to age, duration, body mass index (BMI), HbA1c, or A1cDUR. TAOC increased as logA1cDUR increased (n = 13, r = 0.61, p = 0.028). CRP and sICAM were not related to CGM average glucose but log CRP increased as 3 day glucose standard deviation increased (r = 0.66, p = 0.006). TAOC increased as glucose standard deviation increased (r = 0.63, p = 0.028). Conclusions Increased glucose variability is associated with increased inflammation in adolescents withT1D. Increased TAOC with increasing variability may be an effort to compensate for the ongoing oxidative stress.

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“…25,26 It is worth mentioning that although absolute HbA1c levels were used as indicators of glycemic control, glucose variability was not measured in this study. Hoffman et al reported on 17 adolescents with type 1 diabetes, stating that increased glucose variability is associated with increased inflammation in this group, 43 suggesting that pathogenesis in type-1 diabetes is different from T2D. It would be interesting to determine whether patients in the non-controlled glycemia group had increased instances of intermittent hyperglycemia or whether it was sustained hyperglycemia.…”

“…Many studies in human adults have found no association between glucose variability and consequences of inflammation, such as microvascular or macrovascular complications, arterial stiffness, and carotid intimal thickness. 43 On the other hand, other studies stated that fluctuations in glucose, especially during post prandial periods, heightened the triggering effect on oxidative stress compared to sustained hyperglycemia. 45 The major strength of this study is the stringent procedure we used for the selection of the participants to rule out any acute response to inflammation.…”

Continuous glucose monitoring use and glucose variability in pre-school children with type 1 diabetes

“…The role of GV as a risk factor for developing complications of diabetes remains controversial, however, several reports associate GV with oxidative stress and damage to susceptible organs [15,16] and chromosomes [17]. Consequently, preventing excessive glucose fluctuations early in the disease course could provide long-term benefit for children.…”

The prognostic value of inflammatory and vascular endothelial dysfunction biomarkers in microvascular and macrovascular complications in type 1 diabetes

“…The activity of intercellular adhesion molecule 1 (ICAM-1), present on leukocytes and endothelial cells, may be increased by a number of cytokines [66]. Soluble forms of ICAM-1 (sICAM-1) constitute a biomarker of endothelial damage and inflammation [67]. Elevated levels of sICAM-1 are found in autoimmune conditions, including T1DM [65,66].…”