Electrophysiological studies in newly onset type 2 diabetes without visible vascular retinopathy.

The purpose of this study was to investigate the early alterations of retinal function, assessed with electrophysiology, in newly onset type 2 diabetes patients without vascular retinopathy. Seventeen patients with newly diagnosed type 2 diabetes (duration 7±3 months), without any vascular retinopathy in fundus photographs, were examined with full-field electroretinogram (ERG) and multifocal ERG (mfERG). The results were compared with those of age-matched subjects without diabetes. In the dark-adapted full-field ERG, the a-wave and the 30-Hz flicker implicit times were delayed in diabetes patients compared to controls, P=0.001 and P=0.020. In the first-order kernel of the mfERG, the first positive wave, P1, was delayed in all areas measured. The electrophysiological examinations demonstrate early alterations of retinal function characterised by a delayed a-wave implicit time in the dark-adapted full-field ERG, representing the rod signalling, and alterations in the multifocal ERG reflecting cone and/or postreceptoral function.

Retinopathy in subjects with impaired fasting glucose: the NANSY-Eye baseline report.

AIMS: Network for Pharmacoepidemiology (NEPI) Antidiabetes Study-Eye is a randomized placebo-controlled Swedish trial investigating if treatment with sulphonylurea, in addition to dietary regulation and increased exercise, delays the development of retinopathy in subjects with impaired fasting glucose (IFG). METHODS: Subjects were surveyed in primary care with repeated fasting blood glucose measurements. Those with a mean of two consecutive values >or=5.6 and <6.1 mmol/l were invited to participate. Baseline physical examination included blood pressure and body mass index (BMI). Fundus photos were taken in two fields using 35-mm diafilm. The alternative classification of the Wisconsin Epidemiologic Study of Diabetic Retinopathy was used to classify the retinopathy level. RESULTS: At baseline, 90 men and 64 women with IFG were photographed. Of these, 16 subjects (10%) had mild or very mild retinopathy. There was no difference in occurrence of retinopathy between subjects with known diagnosis of hypertension or not. However, subjects with retinopathy had significantly higher systolic (154 vs. 141 mmHg, p = 0.013) and diastolic (86 vs. 81 mmHg, p = 0.008) blood pressure levels independent of differences in age, sex and known hypertension. There was a corresponding difference in BMI, being greater in subjects with than in those without retinopathy (32.4 vs. 29.2 kg/m(2), p = 0.013). There were no associations between levels of fasting blood glucose or haemoglobin A1c, on the one hand, and retinopathy, on the other. CONCLUSION: Retinopathy may be present even before type 2 diabetes is manifest. It is associated with higher blood pressure levels and higher BMI values, that is, with predominant features of the metabolic syndrome.

Nephropathy, but not retinopathy, is associated with the development of heart disease in Type 1 diabetes: a 12-year observation study of 462 patients.

AIMS: To study the occurrence of heart disease and death in Type 1 diabetic patients and evaluate whether presence of microangiopathy, i.e. nephropathy and retinopathy, was associated with the outcome. METHODS: A 12-year observation study of 462 Type 1 diabetic patients without a previous history of heart disease at baseline who were treated under routine care in a hospital out-patient clinic. RESULTS: A total of 85 patients developed signs of heart disease, i.e. myocardial infarction (n = 41), angina (n = 23), and heart failure (n = 17) and 56 patients died. The mortality for patients without signs of heart disease during the observation period was 7.6% compared with 51% in patients with myocardial infarction (P < 0.001), 26% in patients with angina (P < 0.01) and 65% in patients with heart failure (P < 0.001). The relative risk for death was 9.0 (P < 0.001) and 2.5 (P < 0.05) times higher in patients with macroalbuminuria and microalbuminuria, respectively. The risk for cardiovascular death was 18.3 times (P < 0.001) higher in patients with macroalbuminuria compared with patients with normoalbuminuria. In patients with sight-threatening retinopathy, the relative risk for death was 7.0 times higher (P < 0.01) and the risk for coronary heart disease events 4.4 times higher (P < 0.05) compared with patients with no retinopathy. However, when retinopathy was adjusted for presence of macroalbuminuria, this association disappeared. CONCLUSION: This study shows a high incidence of heart disease in patients with Type 1 diabetes. The worse prognosis was seen in patients with sight-threatening retinopathy and macroalbuminuria and microalbuminuria at baseline. Macroalbuminuria and microalbuminuria were independently associated with a high risk for heart disease and death while the association with sight-threatening retinopathy only occurred in the presence of nephropathy.

Diabetic retinopathy, visual acuity, and medical risk indicators: a continuous 10-year follow-up study in Type 1 diabetic patients under routine care.

The objective of this study was to describe incidence and progression of diabetic retinopathy in relation to medical risk indicators as well as visual acuity outcome after a continuous follow-up period of 10 years in a Type 1 diabetic population treated under routine care. The incidence and progression of retinopathy and their association to HbA(1c), blood pressure, urinary albumin, serum creatinine levels, and insulin dosage were studied prospectively in 452 Type 1 diabetic patients. The degree of retinopathy was classified as no retinopathy, background, or sight-threatening retinopathy, i.e. clinically significant macular edema, severe nonproliferative, or proliferative retinopathy. Impaired visual acuity was defined as a visual acuity <0.5 and blindness as a visual acuity < or =0.1 in the best eye. In patients still alive at follow-up (n=344), 61% (69/114) developed any retinopathy, 45% (51/114) background retinopathy, and 16% (18/114) sight-threatening retinopathy. Progression from background to sight-threatening retinopathy occurred in 56% (73/131). In 2% (6/335), visual acuity dropped to <0.5 and in less than 1% (3/340) to < or =0.1. Patients who developed any retinopathy and patients who progressed to sight-threatening retinopathy had higher mean HbA(1c) levels over time compared to those who remained stable (P<.001 in both cases). Patients who developed any retinopathy had higher levels of mean diastolic blood pressure (P=.036), whereas no differences were seen in systolic blood pressure levels between the groups. Cox regression analysis, including all patients, showed mean HbA(1c) to be an independent risk indicator for both development and progression of retinopathy, whereas mean diastolic blood pressure was only a risk indicator for the incidence of retinopathy. Metabolic control is an important risk indicator for both development and progression of retinopathy, whereas diastolic blood pressure is important for the development of retinopathy in Type 1 diabetes. The number of patients who became blind during 10 years of follow-up was low.

Contrast sensitivity and visual recovery time in diabetic patients treated with panretinal photocoagulation.

PURPOSE: To study patients treated with panretinal photocoagulation regarding contrast sensitivity and visual recovery time after exposure to glare. METHODS: To compare contrast sensitivity and visual recovery-time after exposure to glare in eyes (n=20) from 20 type 1 diabetic patients treated with panretinal photocoagulation for proliferative retinopathy with eyes (n= 19) from 19 un-treated type 1 diabetic patients. Contrast sensitivity was tested with a low contrast acuity chart, before and during exposure to either a uniform background illumination or a spotlight. Visual recovery time was defined as the time required to regain baseline visual acuity during light exposure. RESULTS: Contrast thresholds values were higher in eyes treated with panretinal photocoagulation compared to un-treated eyes before illumination 4.2 +/- 1.2% vs. 3.1 +/- 1.7% (p=0.006), during background illumination 5.8 +/- 5.1% vs. 3.9 +/- 4.8% (p=0.001), and during spotlight exposure 5.6 +/- 2.2% vs. 3.2 +/- 1.8% (p<0.001). Furthermore, recovery time was longer both during background illumination, 20; 5-50 sec vs. 2; 2-80 sec. (md;range), (p<0.001) and during spotlight illumination 27; 5-70 sec vs. 2;1-60 sec. (md;range) (p<0.001). CONCLUSION: Eyes treated with panretinal photocoagulation had higher contrast threshold levels at baseline and during glare, as well as a prolonged visual recovery time compared to un-treated eyes with mild background retinopathy.

Photocoagulation of diabetic macular oedema--complications and visual outcome.

PURPOSE: To describe complications and visual outcome of photocoagulation for clinically significant macular oedema. SUBJECTS AND METHODS: Evaluation of macular oedema and complications of photocoagulation in 194 eyes, defined as subretinal fibrosis, atrophic creep of the pigment epithelium and subretinal neovascularization was based on stereo fundus photo grading. The study included 25 patients with type 1 and 93 patients with type 2 diabetes (age 32 +/- 10 and 65 +/- 9 years, respectively). The statistical evaluations were based on one eye per patient. RESULTS: Follow-up time was 5.5 +/- 2.4 years (mean +/- SD). Complications within 1/3 ODD from the centre of the macula were seen in 4% (1/23) of eyes of patients with type 1 diabetes, compared to 26% (20/76) of eyes among patients with type 2 diabetes (p=0.02). Hard exsudates before treatment were more common in type 2 than in type 1 diabetic eyes, 70/82 vs. 11/23 (p<0.001). In all eyes, hard exsudates were more often associated with subretinal fibrosis or atrophic creep (35/133 eyes) than diffuse oedema (5/44 eyes) (p=0.04). CONCLUSION: Photocoagulation for clinically significant macular oedema with hard exudates, particularly when subfoveally located, was more often associated with subretinal fibrosis or atrophic creep of the pigment epithelium than photocoagulation of oedema without hard exudates. Hard exudates as well as complications after photocoagulation were more common in type 2 than in type 1 diabetes, resulting in poorer visual outcome in this group of patients.

The temporal development of retinopathy and nephropathy in type 1 diabetes mellitus during 15 years diabetes duration.

In this prospective study, the 10- and 15-year incidence and course of retinopathy were examined in relation to medical risk indicators from 3.1 +/- 1.9 (mean -/+ SD) years diabetes duration and onwards in 29 adult type 1 diabetic patients treated under routine care. A total of 28 patients were followed for 10 years and 20 patients for 15 years diabetes duration. After 10 years diabetes duration, 11 patients had developed any retinopathy (ten patients background retinopathy and one patient clinically-significant macular oedema). After 15 years diabetes duration, 16 patients had developed any retinopathy (12 patients developed background retinopathy and four patients developed potentially sight-threatening retinopathy, i.e. clinically significant macular oedema (n = 2) or severe non-proliferative retinopathy (n = 2)). None of the patients developed proliferative retinopathy. No differences were seen in mean HbA1c values between patients without any retinopathy and patients with background retinopathy, whereas patients who developed potentially sight-threatening retinopathy had higher mean HbA1c levels than patients without any retinopathy. Patients who developed potentially sight-threatening retinopathy had higher levels of mean HbA1c both after 10 (9.7 +/- 1.6 vs 6.9 +/- 1.5%; P < 0.05) and 15 years diabetes duration (9.3 +/- 1.2 vs 7.1 +/- 1.3%; P < 0.05), compared to patients without any retinopathy. They also had higher levels of mean HbA1c than patients with background retinopathy after 15 years diabetes duration (9.3 +/- 1.2 vs 7.7 +/- 1.1%; P < 0.05). There were no differences in blood pressure levels between patients who developed retinopathy and those who did not. Only two patients developed clinical signs of nephropathy (urinary albumin 320-1590 mg/l) after 12 and 13 years diabetes duration, respectively. At those time points, both patients had already developed background retinopathy since 2 years. In conclusion, the present study shows that the incidence of retinopathy is associated with the duration of diabetes and that there is a strong association between the degree of metabolic control and development of potentially sight-threatening retinopathy. The study also indicates that the development of retinopathy does not seem to be associated with hypertension or clinical signs of nephropathy.

The incidence of nephropathy in type 1 diabetic patients with proliferative retinopathy: a 10-year follow-up study.

Patients with type 1 diabetes mellitus and with proliferative retinopathy often have a concomitant diabetic nephropathy. However, in cross-sectional studies it has been shown that 35% of patients with proliferative retinopathy do not show signs of diabetic nephropathy. The aim of the present study was to examine the incidence of diabetic nephropathy in type 1 diabetic patients with proliferative retinopathy but without signs of nephropathy. To that end, out of 102 consecutive patients with proliferative retinopathy attending the University Hospital, Lund, in 1986, 24 patients did not show any clinical signs of nephropathy, and were followed for 10 years regarding the development of nephropathy. Their age was 36.7 +/- 9.8 years, age at onset 11.8 +/- 7.5 years, diabetes duration 25.7 +/- 6.9 years and duration of proliferative retinopathy 4.6 +/- 3.8 years (mean +/- S.D.). At entry, no patient had albuminuria (< 30 mg/l), and albumin creatinine clearance ratio was < 0.01 x 10(-3). During the 10-year follow-up period, two of the patients showed isolated higher peaks of elevated urinary albumin, but none of the 24 patients developed persistent microalbuminuria (> or = 30 mg/l). Two patients died before follow-up, but none of these had developed microalbuminuria at the time for death. Based on mean annual measurements, there were no increases in HbA1c, systolic and diastolic blood pressure, and serum creatinine levels. At entry, seven of the patients were treated with antihypertensive drugs and another three patients received such treatment during the study period. In conclusion, in a subgroup of patients with proliferative retinopathy, i.e. without clinical signs of diabetic nephropathy, no patient developed persistent microalbuminuria during a 10-year follow-up period. These results indicate further evidence for at least partly different pathogenic mechanisms behind diabetic retinopathy and nephropathy.

Poor metabolic control, early age at onset, and marginal folate deficiency are associated with increasing levels of plasma homocysteine in insulin-dependent diabetes mellitus. A five-year follow-up study.

In a previous study, we showed that diabetic patients exhibited significantly increased concentrations of total plasma homocysteine (tHcy), but not until the onset of nephropathy. It was suggested that the hyperhomocysteinaemia might contribute to the accelerated atherosclerotic process in diabetic patients. In the present study, we have analysed the main determinants of plasma homocysteine (i.e. serum cobalamin, blood folate and serum creatinine), and also some other parameters related to diabetes mellitus, such as medical history, metabolic and renal quantities, on two occasions with a 5-year interval in 50 patients with insulin-dependent diabetes mellitus, in order to further elucidate the relation between plasma tHcy and diabetes mellitus. The result of the present study shows that diabetic patients with the lowest age at onset and with the poorest metabolic control are those most prone to a rapid increase in plasma tHcy concentration. The increment in plasma tHcy concentration in this group of patients may at least partly be explained by a marginal deficiency of blood folate concentrations.

Pre-eclampsia is a potent risk factor for deterioration of retinopathy during pregnancy in Type 1 diabetic patients.

The aim of the present study was to examine the influence of pregnancy on deterioration of retinopathy in patients with Type 1 diabetes mellitus. Sixty-five pregnant Type 1 diabetic women attending the University Hospital in Lund were studied retrospectively. The degree of retinopathy, and levels of HbA1c and blood pressure 12 months before, during, and 6 months after pregnancy were compared of those of 56 non-pregnant Type 1 diabetic women matched for age and duration of diabetes. For all patients, sight-threatening deterioration of retinopathy did not differ between the pregnancy group (9/65) and the control group (6/56). Over time, pregnant patients had lower HbA1c levels than controls (p < 0.001). Pregnant patients with sight-threatening deterioration of retinopathy had higher HbA1c levels than those without (p = 0.028 and the decrement in HbA1c between the 6-14th and the 20th week of gestation was more pronounced (p = 0.006). In those patients who developed pre-eclampsia during pregnancy, deterioration of retinopathy ocurred more frequently compared to those without pre-eclampsia (4/8 vs 5/65; p = 0.005). In conclusion, sight-threatening deterioration of retinopathy was not more common during pregnancy in IDDM patients than among age- and duration-matched control patients. In pregnant patients, deterioration of retinopathy was associated with the pregestational degree of metabolic control as well as with a rapidly improved glycaemic control acheived during pregnancy. Among those in whom deterioration occurred during pregnancy, pre-eclampsia was a potent risk factor.