Person:

Cavallerano, Jerry

Objective: To assess complication prevalence and identify protective factors in patients with diabetes duration of (\geq)50 years. Characterization of a complication-free subgroup in this cohort would suggest that some individuals are protected from diabetes complications and allow identification of endogenous protective factors. Research Design and Methods: Cross-sectional, observational study of 351 U.S. residents who have survived with type 1 diabetes for (\geq)50 years (Medalists). Retinopathy, nephropathy, neuropathy, and cardiovascular disease were assessed in relation to HbA(_{1c}), lipids, and advanced glycation end products (AGEs). Retrospective chart review provided longitudinal ophthalmic data for a subgroup. Results: A high proportion of Medalists remain free from proliferative diabetic retinopathy (PDR) (42.6%), nephropathy (86.9%), neuropathy (39.4%), or cardiovascular disease (51.5%). Current and longitudinal (the past 15 years) glycemic control were unrelated to complications. Subjects with high plasma carboxyethyl-lysine and pentosidine were 7.2-fold more likely to have any complication. Of Medalists without PDR, 96% with no retinopathy progression over the first 17 years of follow-up did not experience retinopathy worsening thereafter. Conclusions: The Medalist population is likely enriched for protective factors against complications. These factors might prove useful to the general population with diabetes if they can be used to induce protection against long-term complications. Specific AGE combinations were strongly associated with complications, indicating a link between AGE formation or processing with development of diabetic vasculopathy.

Objective: To evaluate the ability of certified retinal imagers to identify presence versus absence of sight-threatening diabetic retinopathy (stDR) (moderate nonproliferative diabetic retinopathy or worse or diabetic macular edema) at the time of retinal imaging in a telemedicine program. Research Design and Methods: Diabetic patients in a primary care setting or specialty diabetes clinic received Joslin Vision Network protocol retinal imaging as part of their care. Trained nonphysician imagers graded the presence versus absence of stDR at the time of imaging. These gradings were compared with masked gradings of certified readers. Results: Of 158 patients (316 eyes) imaged, all cases of stDR (42 eyes [13%]) were identified by the imagers at the time of imaging. Six eyes with mild nonproliferative diabetic retinopathy were graded by the imagers to have stDR (sensitivity 1.00, 95% CI 0.90–1.00; specificity 0.97, 0.94–0.99). Conclusions: Appropriately trained imagers can accurately identify stDR at the time of imaging.

Objectives: To evaluate the effect of pupillary dilation on electronic-ETDRS visual acuity (EVA) in diabetic subjects and to assess post-dilation EVA as a surrogate for pre-dilation visual acuity (VA). Methods and Design: DRCR.net-protocol refraction and EVA were measured pre- and post-dilation in diabetic subjects by independent, masked examiners. Results: In 129 eyes of 66 subjects, median [25th, 75th percentiles] pre-dilation EVA score was 69 [54, 86] (Snellen-equivalent 20/40-1 [20/80-1, 20/20+1]). Pre-dilation VA was ≥20/20, 20/25-20/40, 20/50-20/80, and <20/80 in 29%, 19%, 26%, and 26% of eyes, respectively. Median EVA change post-dilation was -3 letters [-7, 0]. EVA change was ≥15 letters (≥ 3 ETDRS lines) in 9% of eyes and ≥10 letters (≥ 2 ETDRS lines) in 19% of eyes. Extent of change (range +12 to -25 letters) was associated with baseline VA. No relationship was identified between EVA change and gender, race, lens status, refractive error, DR severity, or primary cause of vision loss. Conclusions: In an optimized clinical trial setting, there is a decline in best-corrected EVA after dilation in diabetic subjects. The large range and magnitude of VA change preclude using post-dilation EVA as a surrogate for undilated VA.

Purpose: To compare visual acuity (VA) scores obtained after autorefraction or using a pinhole occluder to scores obtained after refraction according to a standard clinical research protocol. Design: Prospective, comparative case series Participants: One hundred and ten study participants (209 eyes) with diabetes mellitus and a broad range of diabetic retinopathy severity and visual acuity (VA). Methods: VA was measured after autorefraction by a Topcon KR-8000 autorefractor as well as after a Diabetic Retinopathy Clinical Research Network (DRCR.net) protocol manual refraction. The order of testing was randomized and examiners were masked to the source of each refraction. A second VA measurement, utilizing an identical DRCR.net manual refraction, was made in a subset of eyes (N = 144, 69%) in order to establish test-retest variability for comparison purposes. All eyes underwent VA testing using a pinhole occluder. Main Outcome Measures: Best corrected VA as measured by the Electronic Early Treatment Diabetic Retinopathy Study Visual Acuity Test© (E-ETDRS). Results: In all eyes, the median E-ETDRS VA letter score (EVA) obtained after manual refraction (MR-EVA) was 69 (Snellen equivalent 20/40), ranging from 4 to 93 (20/800 to 20/16). The median MR-EVA was slightly better than the median EVA obtained after autorefraction (AR-EVA), with a median difference (AR-EVA – MR-EVA) of −1 letter (25th, 75th percentiles: −4, 2 letters). The absolute difference between AR-EVA and MR-EVA was similar to the test-retest variability of MR-EVA alone. In contrast, MR-EVA was better than EVA obtained using a pinhole occluder (PH-EVA), (median PH-EVA – MR-EVA: −4 letters [−9, 0]), and had significantly less test-retest variability (P<0.001). Generally, the spherical equivalent of autorefraction was slightly more hyperopic (or less myopic) than the spherical equivalent of manual refraction (median difference: +0.25 Diopters [0, +0.63 Diopters]). Conclusions: Given the substantial time and effort required for training and certification of study protocol refractionists, and the similarity between AR-EVA and MR-EVA, further evaluation of autorefraction, but not pinhole occluder testing, as an alternative to the current clinical research gold standard of ETDRS protocol manual refraction in study participants with diabetic retinopathy is warranted.

OBJECTIVE—The aim of this study was to evaluate the regional effects of type 2 diabetes and associated conditions on cerebral tissue volumes and cerebral blood flow (CBF) regulation.

RESEARCH DESIGN AND METHODS—CBF was examined in 26 diabetic (aged 61.6 ± 6.6 years) and 25 control (aged 60.4 ± 8.6 years) subjects using continuous arterial spin labeling (CASL) imaging during baseline, hyperventilation, and CO2 rebreathing. Regional gray and white matter, cerebrospinal fluid (CSF), and white matter hyperintensity (WMH) volumes were measured on a T1-weighted inversion recovery fast-gradient echo and a fluid attenuation inversion recovery magnetic resonance imaging at 3 Tesla.

RESULTS—The diabetic group had smaller global white (P = 0.006) and gray (P = 0.001) matter and larger CSF (36.3%, P < 0.0001) volumes than the control group. Regional differences were observed for white matter (−13.1%, P = 0.0008) and CSF (36.3%, P < 0.0001) in the frontal region, for CSF (20.9%, P = 0.0002) in the temporal region, and for gray matter (−3.0%, P = 0.04) and CSF (17.6%, P = 0.01) in the parieto-occipital region. Baseline regional CBF (P = 0.006) and CO2 reactivity (P = 0.005) were reduced in the diabetic group. Hypoperfusion in the frontal region was associated with gray matter atrophy (P < 0.0001). Higher A1C was associated with lower CBF (P < 0.0001) and greater CSF (P = 0.002) within the temporal region.

CONCLUSIONS—Type 2 diabetes is associated with cortical and subcortical atrophy involving several brain regions and with diminished regional cerebral perfusion and vasoreactivity. Uncontrolled diabetes may further contribute to hypoperfusion and atrophy. Diabetic metabolic disturbance and blood flow dysregulation that affects preferentially frontal and temporal regions may have implications for cognition and balance in elderly subjects with diabetes.

OBJECTIVE Diabetes increases the risk for cerebromicrovascular disease, possibly through its effects on blood flow regulation. The aim of this study was to assess the effects of type 2 diabetes on blood flow velocities (BFVs) in the middle cerebral arteries and to determine the relationship between white matter hyperintensities (WMHs) on magnetic resonance imaging (MRI) and BFVs.

RESEARCH DESIGN AND METHODS We measured BFVs in 28 type 2 diabetic and 22 control subjects (aged 62.3 ± 7.2 years) using transcranial Doppler ultrasound during baseline, hyperventilation, and CO2 rebreathing. WMHs were graded, and their volume was quantified from fluid-attenuated inversion recovery images on a 3.0 Tesla MRI.

RESULTS The diabetic group demonstrated decreased mean BFVs and increased cerebrovascular resistance during baseline, hypo- and hypercapnia (P < 0.0001), and impaired CO2 reactivity (P = 0.05). WMH volume was negatively correlated with baseline BFV (P < 0.0001). A regression model revealed that baseline BFVs were negatively associated with periventricular WMHs, HbA1c (A1C), and inflammatory markers and positively associated with systolic blood pressure (R2 = 0.86, P < 0.0001).

CONCLUSIONS Microvascular disease in type 2 diabetes, which manifests as white matter abnormalities on MRI, is associated with reduced cerebral BFVs, increased resistance in middle cerebral arteries, and inflammation. These findings are clinically relevant as a potential mechanism for cerebrovascular disease in elderly with type 2 diabetes.