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Microvascular abnormalities in pediatric diabetic patients
Anthony T W Cheung1, Amber R Price, Patricia L Duong
1Department of Medical Pathology, University of California, Davis School of Medicine, 95616, USA.
Insights
Pediatric type 1 diabetes patients exhibit microvascular abnormalities, similar to adults, detectable noninvasively. These abnormalities correlate with hemoglobin A1c, not disease duration, suggesting early pathogenesis.
Area of Science:
- Ophthalmology
- Diabetology
- Vascular Biology
Background:
- Microvascular abnormalities are linked to organ damage in adult diabetics.
- The presence and study of these abnormalities in pediatric diabetics were previously limited by technological and methodological constraints.
Purpose of the Study:
- To investigate the presence of microvascular abnormalities in pediatric type 1 diabetes mellitus (T1DM) patients.
- To adapt computer-assisted intravital microscopy (CAIM) for noninvasive in vivo assessment of conjunctival microcirculation in young patients.
Main Methods:
- CAIM was utilized to quantify microvascular abnormalities in the bulbar conjunctiva of 12 pediatric T1DM patients (ages 6-16).
- A severity index (SI) was developed by summing all observed microvascular abnormalities.
- SI in T1DM patients was compared to a control group and correlated with hemoglobin A1c and disease duration.
Main Results:
- All pediatric T1DM patients displayed microvascular abnormalities in the conjunctiva.
- The severity index (SI) was significantly higher in T1DM patients compared to controls (P < 0.0001).
- SI correlated with hemoglobin A1c levels but not with the duration of diabetes.
Conclusions:
- Microvascular abnormalities are present in pediatric T1DM patients, even with short disease duration.
- CAIM is a viable real-time technology for studying conjunctival microvascular changes in pediatric and adult vascular diseases.
- Diabetic pathogenesis may begin before clinical diagnosis or overt symptoms in children.
Abstract:
Microvascular abnormalities are associated with and causative of the development of end-stage organ complications in adult diabetic patients. Whether the same microvascular abnormalities are present in pediatric patients is not known and has not been studied because of a lack of real-time technology, methodology to study young patients, and availability of an appropriate noninvasive site for in vivo studies. We hypothesized that microvascular abnormalities should be present in pediatric patients despite their young age and the relatively short durations of the disease. In this study, computer-assisted intravital microscopy (CAIM) was adapted to blindly quantify microvascular abnormalities in 12 pediatric type 1 diabetic mellitus (T1DM) patients (ages = 6-16 years; mean +/- SD = 11.42 +/- 3.42; duration since diagnosis = 2-14 years; mean +/- SD = 6.75 +/- 3.79) in vivo, using the microcirculation of the bulbar conjunctiva as a noninvasive site. Microvascular abnormalities, commonly found in adult patients, existed in the conjunctival microcirculation of all pediatric T1DM patients in varying degrees despite their relatively young age. A severity index (SI) was developed to reflect the cumulative severity of the microvascular abnormalities and was computed as the summation of all microvascular abnormalities found in each patient. SI for the 12 T1DM patients (mean +/- SD = 7.42 +/- 1.88; median = 8; mode = 9) differed significantly from that for the nondiabetic controls (mean +/- SD = 0.67 +/- 0.78; median = 0.5; mode = 0; P < 0.0001). In addition, SI correlated with hemoglobin A1c levels (mean +/- SD = 9.18 +/- 1.57) of T1DM patients but did not correlate with the duration of disease since diagnosis of the same patients. This observation raises the possibility that diabetic pathogenesis may precede the onset of overt disease or clinical diagnosis. This study confirms that CAIM may represent the availability of a useful real-time technology to study conjunctival microvascular abnormalities in vascular diseases in juvenile as well as adult patients.