Spatial frequency-selective losses with pattern electroretinogram in Type 1 (insulin-dependent) diabetic patients without retinopathy

Summary Neurosensory abnormalities have been implicated in the first stages of diabetic retinopathy. The activity of retinal ganglion cells in 24 Type 1 (insulin-dependent) diabetic patients with short disease duration without retinopathy on fluorescein angiography was investigated by using a pattern electroretinogram in response to sinusoidal gratings of different spatial frequencies (0.6, 1.0, 1.4, 2.2, 4.8 cycles/deg), counterphase modulated at 8 Hz. The pattern electroretinogram reflects, at least in part, the activity of subsets of generators (i. e., ganglion cells) which show spatial selectivity. Mean pattern electroretinogram amplitude was significantly reduced in patients at lower and intermediate, but not at higher spatial frequencies compared with 40 agematched control subjects. At 1.4 cycles/deg the pattern electroretinogram amplitude was significantly correlated (r=0.59) with age at onset (p=0.002) and duration of disease (p=0.002). Our results suggest that in Type 1 diabetic patients without retinopathy, there is an early sensory deficit of specific inner retina neurons which respond preferentially to gratings of medium and large size.     

Electrophysiological assessment of visual function in newlydiagnosed IDDM patients

Summary Electrophysiological tests (electroretinogram, oscillatory potentials, visual evoked potentials, in the basal condition and after photostress) reveal an abnormal function of the visual system in insulin-dependent diabetic (IDDM) patients. The aim of our work was to assess whether electrophysiological abnormalities in visual function exist in newly-diagnosed diabetic patients free of any fluorangiographic signs of retinopathy. Ten control subjects (age 28.7 ± 2.44 years) and ten IDDM patients (age 25.2 ± 6.78 years; disease duration 5.3 ± 3.5 months) in stable metabolic control (HbA_{1 C} 7.5 ± 1.1 %) were evaluated. Flash-electroretinograms and oscillatory potentials were similar in both groups. Visual evoked potentials (VEP) recorded under basal conditions showed that P100 latency was significantly increased in the diabetic patients compared to control subjects (p < 0.01), while N75-P100 amplitude was similar in both groups. The recovery time of VEP after photostress was equivalent in diabetic patients and control subjects. The impaired basal VEPs suggest an early involvement of the nervous conduction in the optic nerve. However, the preserved flash-electroretinogram and the normal recovery time after photostress indicate that a short disease duration does not induce physiopathological changes in the outer retinal layers or in the macular function. [Diabetologia (1995) 38: 804–808] Received: 8 July 1994 and in revised form: 23 December 1994     

Long-term recovery from unawareness,deficient counterregulation and lack of cognitive dysfunction during hypoglycaemia,following institution of rational,intensive insulin therapy in IDDM

Summary Hypoglycaemia unawareness, is a major risk factor for severe hypoglycaemia and a contraindication to the therapeutic goal of near-normoglycaemia in IDDM. We tested two hypotheses, first, that hypoglycaemia unawareness is reversible as long as hypoglycaemia is meticulously prevented by careful intensive insulin therapy in patients with short and long IDDM duration, and that such a result can be maintained long-term. Second, that intensive insulin therapy which strictly prevents hypoglycaemia, can maintain long-term near-normoglycaemia. We studied 21 IDDM patients with hypoglycaemia unawareness and frequent mild/severe hypoglycaemia episodes while on conventional insulin therapy, and 20 nondiabetic control subjects. Neuroendocrine and symptom responses, and deterioration in cognitive function were assessed in a stepped hypoglycaemia clamp before, and again after 2 weeks, 3 months and 1 year of either intensive insulin therapy which meticulously prevented hypoglycaemia (based on physiologic insulin replacement and continuous education, experimental group, EXP, n=16), or maintenance of the original conventional therapy (control group, CON, n=5). At entry to the study, all 21 IDDM-patients had subnormal neuroendocrine and symptom responses, and less deterioration of cognitive function during hypoglycaemia. After intensive insulin therapy in EXP, the frequency of hypoglycaemia decreased from 0.5±0.05 to 0.045±0.02 episodes/patient-day; HbA_1C increased from 5.83±0.18 to 6.94±0.13% (range in non-diabetic subjects 3.8–5.5%) over a 1-year period; all counterregulatory hormone and symptom responses to hypoglycaemia improved between 2 weeks and 3 months, with the exception of glucagon which improved at 1 year; and cognitive function deteriorated further as early as 2 weeks (p<0.05). The improvement in responses was maintained at 1 year. The improvement in plasma adrenaline and symptom responses inversely correlated with IDDM duration. In contrast, in CON, neither frequency of hypoglycaemia, nor neuroendocrine responses to hypoglycaemia improved. Thus, meticulous prevention of hypoglycaemia by intensive insulin therapy reverses hypoglycaemia unawareness even in patients with long-term IDDM, and is compatible with long-term near-normoglycaemia. Because carefully conducted intensive insulin therapy reduces, not increases the frequency of moderate/severe hypoglycaemia, intensive insulin therapy should be extended to the majority of IDDM patients in whom it is desirable to prevent/delay the onset/progression of microvascular complications.Abbreviations IDDM Insulin-dependent diabetes mellitus - IIT intensive insulin therapy - HU hypoglycaemia unawareness - EXP experimental patient group - CON control group     

A 3–19-year follow-up study on diabetic retinopathy in patients diagnosed in childhood and treated with conventional therapy

Few data are available from follow-up studies on diabetic retinopathy in patients diagnosed with insulin-dependent (Type 1) diabetes mellitus in childhood and treated with conventional therapy. We report the results of conventional insulin therapy on development of diabetic retinopathy in 100 children and adolescents (47 females and 53 males), aged 8.3 ± 3.5 (1.2–16.4) years at diagnosis of disease. Oral or intravenous fluorescein angiography was performed during a 3–19 year follow-up in all patients. Retinopathy was staged according to the criteria of the Italian Society of Diabetology (SID). During follow-up, retinopathy was observed in 28 patients (28 %). At the end of follow-up, retinopathy was present in 23 patients and had disappeared in 5. Life-table analysis showed a median disease-free interval of 10.8 years. At 10 years from diagnosis the percentage of patients free of retinopathy was 66 %. Poor metabolic control, age, and degree of pubertal development at diagnosis were the most important risk factors. © 1997 John Wiley & Sons, Ltd.