Strict control of glycaemia: effects on blood flow in the large retinal vessels and in the macular microcirculation.

AIMS: The purpose of this study was to investigate the effect of instituting strict diabetic glycaemic control on the retinal macular microcirculation and to compare this effect with that observed in the main retinal veins. METHODS: In 28 insulin dependent diabetic patients with poor glycaemic control a regimen of strict diabetic control, consisting of four daily insulin injections was instituted and maintained for 6 months. Retinal haemodynamics were investigated in the macular microcirculation by the blue field simulation technique and in the major retinal veins by a combination of bidirectional laser Doppler velocimetry and monochromatic fundus photography. Progression of diabetic retinopathy was assessed from fundus photographs taken at baseline and at the end of the study. RESULTS: Institution of strict diabetic control resulted in a significant increase in leucocyte velocity in the macular circulation (p = 0.013). No significant difference in this increase was observed between eyes that showed progression (n = 8) and no progression (n = 20) of retinopathy during the study. Significant correlations were found between relative changes over time of blood flow measured in the main retinal veins and relative changes of leucocyte velocity determined in the macular microcirculation at 2 months (p = 0.008) and 6 months (p = 0.001) but not at 5 days (p = 0.49). In the eight eyes that showed progression of retinopathy, the product of leucocyte velocity and density at baseline was significantly higher than normal (p < 0.05). During the length of this study, this product was also significantly higher in the eight eyes that showed retinopathy progression than in the 20 eyes that did not show progression (p = 0.005). CONCLUSION: Our results suggest that increased flow in the macular microcirculation may be associated with progression of retinopathy, thus supporting the hypothesis that increased blood flow may play a role in the development of diabetic microangiopathy. Although there are correlations between the changes detected in the macular microcirculation and those measured in the main retinal vessels, there are also differences which need to be further investigated in order to better understand pathogenetic mechanisms.

Strict metabolic control and retinal blood flow in diabetes mellitus.

The effects of strict diabetic control on retinal haemodynamics were studied to elucidate whether such effects are associated with retinopathy changes. In 28 patients with poorly controlled insulin dependent diabetes mellitus and non-proliferative retinopathy, retinal haemodynamics were investigated at baseline, 5 days, 2 months, and 6 months after the institution of strict diabetic control using the bidirectional laser Doppler velocimetry technique and monochromatic fundus photography. Changes in retinal blood flow measured in a major retinal vein (Q) on the fifth day of strict diabetic control correlated significantly with changes in retinopathy level observed at the end of the 6 months of this study (rank correlation 0.65, p < 0.01). On the fifth day of strict diabetic control, 16 out of 20 eyes that showed no progression (NP) of retinopathy at the end of the study had decreases in Q, whereas six out of eight eyes that showed progression (P) had increases in Q. The difference in these changes in Q between P and NP eyes was statistically significant (one way analysis of variance, p = 0.001). No significant changes in Q were detected at 2 months or 6 months. Following the institution of strict diabetic control, no significant changes in time were detected in the regulatory response to 100% oxygen breathing characterised as the percentage decrease in Q at 4-6 minutes of oxygen breathing (analysis of variance, p = 0.36). Changes in Q following institution of strict diabetic control are associated with progression of retinopathy. Measurements described in this study may help identify diabetic patients at risk of progression when their metabolic control is improved.

Evaluation of new rapid office test for microalbuminuria and its comparison to fully quantitative radioimmunoassay.

A novel enzyme-linked immunosorbent assay (ELISA [Dialbumin]) for rapid office measurement of microalbuminuria was evaluated and its performance compared with that of a commercially available radioimmunoassay (double-antibody albumin). Urine samples containing between 0.75 and 1800 micrograms/ml of albumin were obtained from 31 diabetic patients and assayed by both methods. A comparison of the paired values obtained from the two methods gave a correlation coefficient of greater than 0.99. The Dialbumin assay, which used detachable eight-well strips (1 strip/sample), 10-min incubation, tap water wash, and a 2-min color development step, was read on both an ELISA reader and a hand-held analytical device (Acc-U-Dial) designed specifically for this test. The findings of this study indicate that the Dialbumin assay, used in conjunction with the Acc-U-Dial device, affords a rapid, convenient, and sensitive method for quantitative determination of a broad range (0.3-1280 micrograms/ml) of urinary albumin levels in the office setting.

Diabetic glycemic control and retinal blood flow.

The effect of strict glycemic control on retinal volumetric blood flow rate (Q) was investigated in 13 insulin-dependent diabetic patients with laser Doppler velocimetry and monochromatic fundus photography. Strict glycemic control was achieved by glucose monitoring and four daily insulin injections. Q was determined in a major retinal vein at baseline and then 5 days, 2 mo, and 6 mo after the institution of strict control. Level of retinopathy was assessed from stereocolor fundus photographs taken at baseline and 6 mo. After 6 mo of strict diabetic control, five eyes demonstrated progression (P) by one or more retinopathy levels, and eight eyes showed no progression (NP). At 5 days, there was a significant decrease in Q of 1.4 +/- 0.9 microliters/min (P less than 0.005) in NP eyes and a nonsignificant increase in Q of 1.2 +/- 1.7 microliters/min in P eyes. Changes in Q from baseline observed at 5 days were strongly correlated with changes in retinopathy level at 6 mo (r = 0.79, P less than 0.005). No significant changes in Q from baseline were observed at 2 and 6 mo. A lack of decrease in Q at 5 days was associated with the progression of retinopathy that occurs in some patients after the institution of strict glycemic control and may serve as a predictor for progression of retinopathy.

Retinal vascular autoregulation in diabetes mellitus.

The blue field entoptic technique was used to study autoregulation of the macular retinal circulation in response to acute alterations of intraocular pressure in 71 diabetic eyes and 30 normals matched for age, systemic blood pressure, and ophthalmic artery diastolic pressure. IOPmax, the maximal intraocular pressure at which flow is maintained normal by autoregulation, was normal in eyes with no retinopathy (30 +/- 3.2 mm Hg) but decreased with progression of retinopathy, approaching the resting intraocular pressure in eyes with proliferative retinopathy. The hyperemia observed by normals to an acute reduction of intraocular pressure was not observed frequently in the diabetics with no retinopathy. The frequency of observation of the hyperemia decreased with progression of retinopathy and was uniformly absent in eyes with proliferative retinopathy. A group of eyes with minimal microangiopathy was found to have an abnormal IOPmax and no hyperemic response. The prognostic significance of these parameters remains to be established.

Metoclopramide to treat gastroparesis due to diabetes mellitus: a double-blind, controlled trial.

Ten patients with diabetic gastroparesis were selected for a randomized, double-blind, controlled trial of metoclopramide. Each patient had longstanding insulin-requiring diabetes mellitus and symptoms of gastric stasis. The patients were evaluated for the symptoms of gastric stasis and radionucleotide gastric emptying was measured before the patients entered the study and after they were given either metoclopramide or placebo treatment. Metoclopramide, 10 mg orally, stimulated an increase in the rate of gastric emptying (56.8% +/- 7.4%) in contrast to the response to placebo (37.6% +/- 7.7%) (p less than 0.01). The overall symptoms and symptoms of vomiting were markedly reduced during metoclopramide treatment in contrast to those during placebo treatment. Before the study five patients were constipated (less than three bowel movements per week); during metoclopramide treatment the patients' bowel habits were improved. There was a poor correlation between improved gastric emptying and decreased symptoms. Metoclopramide may improve symptoms of diabetic gastric stasis through two mechanisms: its peripheral effect on gastric smooth muscle, which increases gastric emptying; and its central effects on the chemoreceptor vomiting zone, which decrease nausea.

Comparison of clinical couse and sequential electrophysiological tests in diabetics with symptomatic polyneuropathy and its implications for clinical trials.

The use of electrophysiological (EP) tests as the primary basis for determining outcome in clinical trials of therapy for symptomatic diabetic polyneuropathy, and the frequently short duration of such trials, is based on assumptions at variance with the pathology and natural history of this disorder and with the evidence that the commonly employed EP tests predominantly reflect the status of the large myelinated nerve fibers. The course of painful, distal symmetrical, primarily sensory polyneuropathy was studied in nine chronic diabetics, aged 21--59 yr, selected for the absence of other forms of diabetic neuropathy, other causes of neuropathy, and other significant illness. All were treated with modifications of diet, insulin, and a daily multivitamin tablet, and, on a randomized basis, also received either placebo or myo-inositol tablets. Initially, and after 2, 4, and 6 mo, a standardized questionnaire was used to assess symptoms, and a standardized neurological examination and battery of EP tests were performed. A minimum of 6 mo was found necessary to assess the clinical course of this syndrome. Clinical improvement occurred in both legs and arms in four patients, as judged by improvement both in symptoms and in the extent of deficits in pinprick and temperature perception; abnormalities in sensory modalities mediated by large myelinated fibers, however, were generally unaltered after 6 mo. A nonuniform distribution of abnormal EP tests of sensory components of the commonly studied nerves of the leg and arm was demonstrated in the study group at the outset, and clinical improvement was not accompanied by evidence of any consistent pattern of improvement in the initially abnormal EP tests. A significant fraction of chronic diabetics with painful, distal symmetrical, primarily sensory polyneuropathy selected by standard criteria appear to have potential for clinical improvement over 6 mo, but primarily in sensory modalities that make it inappropriate to use the common EP tests as the primary basis of judging outcome.

Unusual presentation of ocular toxocariasis in friends.

Two cases of presumed ocular toxocariasis are reported in 19-year-old college students. One presented with an acute exudative intraocular inflammation, with marked peripheral eosinophilia, while the other had only minimal inflammatory changes of the disc and vitreous. Both had elevated Toxocara antibody titers by the enzyme-linked immunosorbent assay (ELISA) method. The simultaneous occurrence of ocular toxocariasis in friends and the early presentation and detection of their ocular lesions make these 2 cases interesting. The presence of positive laboratory data with only minimal clinical disease in one of the cases suggests that ocular toxocariasis may be more common than is usually appreciated.