Interdisciplinary treatment of diabetes mellitus in a military treatment facility.

The American Diabetes Association emphasizes interdisciplinary management as the standard of care for patients with diabetes. Many times, however, interdisciplinary means various health care professionals treating a patient but not necessarily interacting with each other regarding the patient's care. Recently, Tripler Army Medical Center replicated the Joslin Diabetes Center's diabetes outpatient intensive treatment program as part of a Joslin Diabetes Center/Department of Defense/Veteran's Administration research collaboration. Tripler Army Medical Center named this interdisciplinary program Holopono, which is Hawaiian for success. Holopono is a team of health care professionals providing integrated care and education to a group of diabetes patients over 3.5 days. Individual care management, aided by an Internet-based telemedicine system, then continues for 1 year after entry into the program. This article describes the Holopono program, the role of each team member, and how the team functions together to provide comprehensive diabetes care.

Stereo nonmydriatic digital-video color retinal imaging compared with Early Treatment Diabetic Retinopathy Study seven standard field 35-mm stereo color photos for determining level of diabetic retinopathy.

OBJECTIVE: To evaluate the ability to determine clinical levels of diabetic retinopathy, timing of next appropriate retinal evaluation, and necessity of referral to ophthalmology specialists using stereoscopic nonmydriatic digital-video color retinal images as compared with Early Treatment Diabetic Retinopathy Study (ETDRS) seven standard field 35-mm stereoscopic color fundus photographs. DESIGN: Prospective, clinic-based, comparative instrument validation study. PARTICIPANTS: Fifty-four patients (108 eyes) with type 1 or type 2 diabetes mellitus selected after chart review from a single center to include the full spectrum of diabetic retinopathy. METHODS: Nonsimultaneous 45 degrees -field stereoscopic digital-video color images (JVN images) were obtained from three fields with the Joslin Vision Network (JVN) system before pupil dilation. Following pupil dilation, ETDRS seven standard field 35-mm stereoscopic color 30 degrees fundus photographs (ETDRS photos) were obtained. Joslin Vision Network images and ETDRS photos were graded on a lesion-by-lesion basis by two independent, masked readers to assess ETDRS clinical level of diabetic retinopathy. An independent ophthalmology retina specialist adjudicated interreader disagreements in a masked fashion. MAIN OUTCOME MEASURES: Determination of ETDRS clinical level of diabetic retinopathy, timing of next ophthalmic evaluation of diabetic retinopathy, and need for prompt referral to ophthalmology specialist. RESULTS: There was substantial agreement (kappa = 0.65) between the clinical level of diabetic retinopathy assessed from the undilated JVN images and the dilated ETDRS photos. Agreement was excellent (kappa = 0.87) for suggested referral to ophthalmology specialists for eye examinations. Comparison of individual lesions between the JVN images and the ETDRS photos and for interreader comparisons were comparable to the prior ETDRS study. CONCLUSIONS: Undilated digital-video images using the JVN system were comparable photographs for the determination of diabetic retinopathy level. The results validate the agreement between nonmydriatic JVN images and dilated ETDRS photographs and suggest that this digital technique may be an effective telemedicine tool for remotely determining the level of diabetic retinopathy, suggesting timing of next retinal evaluation and identifying the need for prompt referral to ophthalmology specialists. Thus, the JVN system would be an appropriate tool for facilitating increased access of diabetic patients into recommended eye evaluations, but should not be construed as a paradigm that would replace the need for comprehensive eye examinations.

High-dose vitamin E supplementation normalizes retinal blood flow and creatinine clearance in patients with type 1 diabetes.

OBJECTIVE: To determine the effectiveness of vitamin E treatment in normalizing retinal blood flow and renal function in patients with <10 years of type 1 diabetes. RESEARCH DESIGN AND METHODS: An 8-month randomized double-masked placebo-controlled crossover trial evaluated 36 type 1 diabetic and 9 nondiabetic subjects. Subjects were randomly assigned to either 1,800 IU vitamin E/day or placebo for 4 months and followed, after treatment crossover, for a further 4 months. Retinal blood flow was measured using video fluorescein angiography, and renal function was assessed using normalized creatinine clearance from timed urine collections. RESULTS: After vitamin E treatment, serum levels of vitamin E were significantly elevated (P<0.01) in both type 1 diabetic and control patients. Hemoglobin A1c was not affected by vitamin E treatment. Diabetic patient baseline retinal blood flow (29.1+/-7.5 pixel2/s) was significantly (P = 0.030) decreased compared with that of nondiabetic subjects (35.2+/-7.2 pixel2/s). After vitamin E treatment, diabetic patient retinal blood flow (34.5+/-7.8 pixel2/s) was significantly increased (P<0.001) and was comparable with that of nondiabetic subjects. Additionally, vitamin E treatment significantly (P = 0.039) normalized elevated baseline creatinine clearance in diabetic patients. CONCLUSIONS: Oral vitamin E treatment appears to be effective in normalizing retinal hemodynamic abnormalities and improving renal function in type 1 diabetic patients of short disease duration without inducing a significant change in glycemic control. This suggests that vitamin E supplementation may provide an additional benefit in reducing the risks for developing diabetic retinopathy or nephropathy.

Joslin Vision Network Validation Study: pilot image stabilization phase.

PURPOSE: This preliminary study is designed to evaluate the quality of initial images obtained using the Joslin Vision Network (JVN) image capture and retrieval system. METHODS: Digitized images of 18 patients (36 eyes) were obtained using Topcon Non-mydriatic Fundus Camera and various imaging protocols as described for each series of images. Level of retinopathy ranged from no diabetic retinopathy to proliferative diabetic retinopathy. Images were reviewed and evaluated in comparison to medical record notes and Early Treatment Diabetic Retinopathy Study (ETDRS) seven-standard field stereoscopic 35-mm retinal fundus photographs--when available--to determine the ability of JVN digitized images to allow appropriate diagnosis and clinical management. JVN images were also evaluated for presence of photographic artifacts and stereoscopic presentation. The various displays and relative value of each JVN display were also evaluated. RESULTS: Using combinations of JVN image displays, JVN images were shown to match diagnosed level of diabetic retinopathy as determined from record notes and/or ETDRS seven-standard field stereoscopic 35-mm retinal fundus photography. Viewing images with various combinations of JVN image displays delineates possible sources of artifacts in JVN images. Areas to guide future image capture and image reading are identified. CONCLUSIONS: The JVN image capture system and reading of images by certified readers should allow appropriate photodiagnostic information to support the JVN, the diabetes mellitus disease management telemedicine initiative of the Joslin Diabetes Center. A rigid, full-scale, masked study to compare the Joslin Vision Network to seven-standard field stereoscopic 35-mm retinal fundus photography should be pursued to validate the image-gathering and image-reading strategy to support the Joslin Vision Network.

Risk factors for high-risk proliferative diabetic retinopathy and severe visual loss: Early Treatment Diabetic Retinopathy Study Report #18.

PURPOSE: To identify risk factors for the development of high-risk proliferative diabetic retinopathy (PDR) and for the development of severe visual loss or vitrectomy (SVLV) in eyes assigned to deferral of photocoagulation in the Early Treatment Diabetic Retinopathy Study (ETDRS). METHODS: Multivariable Cox models were constructed to evaluate the strength and statistical significance of baseline risk factors for development of high-risk PDR and of SVLV. RESULTS: The baseline characteristics identified as risk factors for high-risk PDR were increased severity of retinopathy, decreased visual acuity (or increased extent of macular edema), higher glycosylated hemoglobin, history of diabetic neuropathy, lower hematocrit, elevated triglycerides, lower serum albumin, and persons with mild to moderate nonproliferative retinopathy, younger age (or type 1 diabetes). The predominant risk factor for development of SVLV was the prior development of high-risk PDR. The only other clearly significant factor was decreased visual acuity at baseline. In the eyes that developed SVLV before high-risk proliferative retinopathy was observed, baseline risk factors were decreased visual acuity (or increased extent of macular edema), older age (or type 2 diabetes), and female gender. CONCLUSIONS: These analyses supported the view that the retinopathy-inhibiting effect of better glycemic control extends across all ages, both diabetes types, and all stages of retinopathy up to and including the severe nonproliferative and early proliferative stages and the possibility that reducing elevated blood lipids and treating anemia slow the progression of retinopathy.

Vascular endothelial growth factor and severity of nonproliferative diabetic retinopathy mediate retinal hemodynamics in vivo: a potential role for vascular endothelial growth factor in the progression of nonproliferative diabetic retinopathy.

PURPOSE: To determine the effect of vascular endothelial growth factor and retinopathy level on retinal hemodynamics in nondiabetic and diabetic rats and to evaluate retinal hemodynamics in nondiabetic and diabetic patients. METHODS: Forty-eight diabetic and 22 nondiabetic patients had their diabetic retinopathy levels determined from fundus photographs according to Early Treatment Diabetic Retinopathy Study (ETDRS). Fluorescein angiograms were recorded from the left eye by video fluorescein angiography. Retinal blood flow was calculated from the digitized angiograms. Human recombinant vascular endothelial growth factor or vehicle alone was injected intravitreally into 13 nondiabetic and 11 diabetic rats. RESULTS: Retinal blood flow decreased 33% in patients with ETDRS retinopathy level 10 compared with control patients (P = .001) and increased sequentially in more advanced stages of retinopathy, with a strong correlation between retinal blood flow and retinopathy level (r2 = 0.434, P = .001). In the diabetic rats, retinal blood flow was decreased 35.6% (P = .01). Vascular endothelial growth factor maximally increased retinal blood flow by 36.1% in nondiabetic rats after 25 minutes (P = .001) and by 73.7% in diabetic rats after only 5 minutes (P = .01) and caused a greater response in diabetic than in nondiabetic rats. CONCLUSIONS: Retinal blood flow increases with advancing nonproliferative diabetic retinopathy in humans, and diabetes accentuates the vascular endothelial growth factor-induced increase in retinal blood flow and venous dilation in rats. Vascular endothelial growth factor may contribute to the changes in retinal hemodynamics and morphology observed in early diabetic retinopathy.

Retinal blood flow changes in patients with insulin-dependent diabetes mellitus and no diabetic retinopathy.

PURPOSE: The authors investigated retinal blood flow changes in patients with insulin-dependent diabetes mellitus (IDDM) and no diabetic retinopathy compared to age-matched subjects without diabetes. They also investigated whether blood glucose levels could modulate retinal blood flow in these patients with diabetes and whether this modulation would impact retinal blood flow data used in cross-sectional studies assessing changes in retinal blood flow. METHODS: Retinal blood flow was measured using video fluorescein angiography, and blood glucose levels were manipulated using glucose clamp methodologies with continuous basal insulin replacement. Blood glucose levels were clamped at 100, 200, and 300 mg/dl. Retinal blood flow measurements were performed at each blood glucose level after subjects had been stabilized for an hour at each of the different blood glucose levels. RESULTS: Retinal blood flow was found to be significantly decreased (P< 0.01) in the group of patients with no diabetic retinopathy (19.4 +/- 4.6 arbitrary units [AU]) compared to retinal blood flow in subjects without diabetes (28.7 +/- 6.4 AU). During glucose clamp adjustment of blood glucose levels, it was found that as blood glucose levels were increased from euglycemia (100 mg/dl) to 200 mg/dl and to 300 mg/dl, retinal blood flow was significantly increased at the 200 mg/dl level (21.5 +/- 4.7 AU, P < 0.05) and at the 300 mg/dl level (25.9 +/- 8.8 AU, P <0.01) compared to the 100 mg/dl level (16.3 +/- 3.8 AU). In addition, the retinal blood flow at the 100 and 200 mg/dl levels was significantly reduced (P < 0.01) compared to nondiabetic retinal blood flow (28.7 +/- 6.4 AU). CONCLUSIONS: Retinal blood flow was found to be decreased in patients with IDDM with no diabetic retinopathy, and acute elevations in blood glucose levels resulted in increased retinal blood flow in these patients. The acute modulation of retinal blood flow by blood glucose levels should be considered in cross-sectional studies investigating retinal blood flow changes in patients with diabetes. The results from this study indicate that if blood glucose levels are not accounted for in the analyses, larger populations would have to be studied to demonstrate statistically significant differences between groups with and without diabetes.

Cardiovascular autonomic neuropathy and proliferative diabetic retinopathy.

PURPOSE: To determine prospectively whether cardiovascular autonomic neuropathy is a risk factor for proliferative diabetic retinopathy. METHODS: A five-year follow-up study of 88 diabetic persons was performed at a center providing primary and specialized care for diabetes. Participants were white, insulin-dependent patients with diabetes of 15 to 21 years' duration. The primary end point was the presence of proliferative diabetic retinopathy, seen either on fundus photography or ophthalmologic examination. Cardiovascular autonomic neuropathy was measured at baseline by using a standard protocol. RESULTS: Fourteen patients developed proliferative diabetic retinopathy during follow-up. One measure of cardiovascular autonomic neuropathy, the 30:15 ratio, the heart rate variation at the 30th beat compared with that at the 15th beat, was lower among patients with proliferative diabetic retinopathy (P = .0049) The risk of proliferative diabetic retinopathy in patients with an abnormal cardiovascular autonomic neuropathy index was 2.59, although the estimate was not statistically significant because of the small number of patients who developed proliferative diabetic retinopathy. CONCLUSIONS: This study provides prospective evidence that cardiovascular autonomic neuropathy is associated with proliferative diabetic retinopathy. In addition to ocular determinants of proliferative diabetic retinopathy, systemic risk factors also should be considered when examining patients with diabetes mellitus.

Influence of HLA-DR phenotype and myopia on the risk of nonproliferative and proliferative diabetic retinopathy.

The relationship between HLA-DR phenotype, refractive error, and risk of both nonproliferative and proliferative diabetic retinopathy was studied among 227 insulin-dependent diabetics participating in a case-control study of diabetic retinopathy. In the absence of myopia, risk of both proliferative and nonproliferative diabetic retinopathy was increased for HLA-DR phenotypes 4/0, 3/0, and X/X (HLA susceptible) compared to HLA-DR phenotypes 3/4, 3/X, and 4/X (HLA nonsusceptible). Odds ratios equalled 11.8 and 7.4 respectively. In the presence of myopia this increased risk associated with HLA status was abolished. Myopia decreased the risk of proliferative and nonproliferative diabetic retinopathy among HLA-susceptible individuals, odds ratio equalled .09 and .09, but had no protective influence among HLA-nonsusceptible individuals.

Multiple factors in the prediction of risk of proliferative diabetic retinopathy.

To identify risk factors for the development of proliferative diabetic retinopathy, we compared 111 patients with longstanding insulin-dependent diabetes who had proliferative retinopathy (cases) with 81 patients with diabetes of similar duration (an average of 26 years) who did not have proliferative diabetic retinopathy (controls). The cases had diabetes that was more difficult to manage, as evidenced by their more frequent blood sugar levels above 200 mg per deciliter (11 mmol per liter) on routine clinic visits (odds ratio, 1.6 for each increment of 10 per cent in the relative frequency), and they expended less effort in managing their diabetes, as indicated by their less frequent testing of urine for sugar (odds ratio, 0.3). Among those who did not have myopia, the cases also had an excess of the HLA-DR phenotypes 4/0, 3/0, or X/X (odds ratio, 10.0). Among those with myopia, these phenotypes did not carry an increased risk of proliferative retinopathy. These results support a multifactorial model for the development of proliferative diabetic retinopathy; however, the mechanisms of action of the identified factors remain unknown.

Neovascular glaucoma and vitreous hemorrhage following cataract surgery in patients with diabetes mellitus.

The potential complications of cataract surgery in the general population are well known. In addition, cataract extraction in the patient with diabetes mellitus is associated with other potential complications common to this disease: neovascular glaucoma and acceleration of proliferative diabetic retinopathy with or without vitreous hemorrhage. We analyzed the records of 154 patients with diabetes mellitus who had undergone standard intracapsular cataract extraction in one eye only with the other eye serving as the unoperated control eye. We were able to determine the status of the diabetic retinopathy before the operation and to note the development of vitreous hemorrhage and rubeosis iridis/neovascular glaucoma after the operation. If either event occurred within six weeks of the surgery, it was considered to be a complication of the cataract extraction. Intracapsular cataract extraction in this diabetic population, without regard of the preoperative status of the retinopathy, was associated with a statistically significant incidence of postoperative rubeosis iridis/neovascular glaucoma (7.8% vs 0%). In patients with preoperative active proliferative diabetic retinopathy, the risk of developing postoperative rubeosis iridis/neovascular glaucoma was even higher (40% vs 0%). There was also a statistically significant incidence of vitreous hemorrhage after surgery in eyes with no diabetic retinopathy or background diabetic retinopathy (6.5% vs 0%). In patients with active proliferative diabetic retinopathy, there was an increased incidence of vitreous hemorrhage after surgery (20% vs 6.5%), but this was not statistically significant due to the small number of patients studied. Possible explanations for these findings are explored and therapeutic and prophylactic measures recommended.

Diabetic retinopathy in Joslin Clinic patients with adult-onset diabetes.

While only a small proportion of adult-onset diabetic patients develop vision threatening retinopathy, this group makes up a major portion of those diabetics seeking ophthalmologic care. Fifty-three percent of patients having fundus photographs at the W.P. Beetham Eye Unit of the Joslin Clinic developed diabetes at the age of 20 or over, and almost 30% at the age of 40 or over. Twenty-two percent of all patients seen with proliferative retinopathy were in this latter group. Ten of 54 patients with proliferative retinopathy in the greater than or equal to 40 onset group were not taking insulin. The older onset patients who developed proliferative retinopathy did so after shorter durations of diabetes and with more visual disability than younger onset patients. Macular edema was more common in adult-onset patients, and its presence in a patient less than 50 years old was usually associated with proliferative or preproliferative retinopathy.