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Biomedical subjects

C D Agardh

Publications and source records attributed to C D Agardh.

At least 19 recordsLinked to original sources

The association between retinopathy, nephropathy, cardiovascular disease and long-term metabolic control in type 1 diabetes mellitus: a 5 year follow-up study of 442 adult patients in routine care.

The aim of the present study was to examine mean HbA1c and blood pressure levels during a 5 year period in 442 type 1 adult diabetic patients in relation to the incidence and progression of retinopathy, nephropathy and to cardiovascular morbidity and mortality. The study showed, that in patients under routine care at a diabetic unit with four visits to the out-patient clinic per year, the intraindividual coefficient of variation for HbA1c values was 11 +/- 4% (mean +/- S.D.), and 7 +/- 3 and 8 +/- 2% for systolic and diastolic blood pressure, respectively. In 121 patients without retinopathy at entry, the 5 year incidence of any retinopathy was 47% (n = 57). Patients who developed retinopathy had higher mean HbA1c levels (P < 0.01), as well as mean systolic (P < 0.01) and diastolic (P < 0.05) blood pressure levels. In 123 patients with background retinopathy at entry, progression to severe retinopathy, i.e. clinically significant macular oedema, severe non-proliferative or proliferative retinopathy, occurred in 41% (n = 51). In those patients, the degree of metabolic control was worse (P < 0.001), the systolic (P < 0.05) and diastolic (P < 0.01) blood pressure levels were higher. The patients were stratified into four groups according to their urinary albumin concentration at entry: (1) normal albuminuria (< 12.5 mg/l), (2) borderline albuminuria (12.5-30 mg/l), (3) microalbuminuria (31-299 mg/l), i.c. incipient nephropathy and (4) clinical nephropathy (> or = 300 mg/l). An increase of urinary albumin concentration in patients who had normoalbuminuria or borderline albuminuria at entry was associated with mean HbA1c levels (r = 0.24, P < 0.01 and r = 0.27, P < 0.01, respectively). No such association was seen in patients with microalbuminuria or clinical nephropathy at entry. There was no association between the increase of urinary albumin level and mean systolic blood pressure levels in patients who had normoalbuminuria and microalbuminuria at entry. In contrast, there was an association between the increase of urinary albumin level in patients with borderline albuminuria (r = 0.36, P < 0.001), clinical nephropathy (r = 0.26, P < 0.05) and mean systolic blood pressure (P < 0.05). There was no association between the increase of urinary albumin levels and mean diastolic blood pressure in any of the albuminuria groups. As for the incidence of cardiovascular disease, renal insufficiency or death, the duration of diabetes (P < 0.01), urinary albumin concentration at entry (P < 0.001), mean systolic blood pressure (P < 0.05) and treatment with loop diuretics (P < 0.001) were but age, age at onset of diabetes, mean levels of HbA1c and diastolic blood pressure as well as treatment with beta- or Ca-blockers or ACE inhibitors were not related to these end-points. In conclusion, the present study showed that there was an association between the degree of metabolic control and both development and progression of retinopathy and progression of nephropathy of early stages in type 1 diabetic patients treated under routine conditions. Moreover, both the incidence and progression of retinopathy and progression of nephropathy at later stages were also associated with the long-term blood pressure levels. However, HbA1c levels were not associated with morbidity and mortality in cardiovascular disease or development of renal insufficiency.

Adult

Artery blood pressure oscillation after active standing up: an indicator of sympathetic function in diabetic patients.

Dynamic artery blood pressure (Finapres) response to active standing up, normally consisting of initial rise, fall and recovery above the baseline (overshoot), was compared with the early steady-state artery blood pressure level to measure sympathetic vasomotor function in healthy subjects (n = 23, age 35 +/- 9 years; mean +/-SD) and in type I diabetic patients without autonomic neuropathy (AN) (group 1: n = 18, 38 +/- 13 years), with AN but no cardiovascular drugs (group 2a: n = 7, 44 +/- 11 years) and with both AN and cardiovascular drugs (group 2b: n = 10, 47 +/- 7 years). Systolic and diastolic overshoot were similar in the control (15 +/- 13/15 +/- 11 mmHg) and group 1 subjects. Systolic overshoot disappeared in 57% of patients in group 2a (-1 +/- 9 mmHg; P < 0.03), whereas artery blood pressure still overshot in diastole (8 +/- 7 mmHg; NS). Systolic overshoot disappeared in all patients in group 2b (-22 +/- 22 mmHg; P < 0.0006) and diastolic overshoot disappeared in 60% of these patients (-6 +/- 16 mmHg; P = 0.0006). Systolic early steady-state level was not lower in group 2a than in group 1 (NS), but it was impaired in group 2b (P < 0.006), in which six diabetic patients had a pathological response beyond the age-related reference values. There was a strong association between the overshoot and steady-state levels (P for chi 2 < 0.001, n = 58). Overshoot of the control subjects and patients in group 2b correlated to their respective steady-state blood pressure levels (r > or = 0.76; P < or = 0.001). In conclusion, baroreceptor reflex-dependent overshoot of the artery blood pressure after active standing up diminishes with the development of AN and it is associated with the early steady-state level of the artery blood pressure.

Adult

Restitution of neurophysiological functions, performance, and subjective symptoms after moderate insulin-induced hypoglycaemia in non-diabetic men.

The restoration of cognitive function was studied in 10 healthy men aged 26 years (25.5 +/- 1.2 years; mean +/- SD) after insulin-induced hypoglycaemia (arterialized blood glucose 2.5 +/- 0.4 mmol l-1) for 62 +/- 8 min. Another group of six men participated in a single blind sham study for comparison. The hypoglycaemic event caused a significant increase (p = 0.006) in serum adrenaline levels. Ratings of adrenergically mediated symptoms increased during hypoglycaemia (p = 0.006), as did neuroglycopenic symptoms (p = 0.002), although neuroglycopenia ratings increased in both studies. During hypoglycaemia, P300 amplitudes in a relatively demanding visual search task decreased (p = 0.02), whereas easier tasks were unaffected. The amplitudes were restored after 40 min of normoglycaemia. Reaction time deteriorated after restoration of normoglycaemia, suggesting an effect of hypoglycaemia on learning. Thus, hypoglycaemia at a blood glucose level that is common among patients treated with insulin causes clear cognitive dysfunction, although restoration of the cognitive dysfunction to normal was fast.

Adult

The effect of the non-ionic contrast medium iohexol on glomerular and tubular function in diabetic patients.

The effect of the non-ionic contrast medium iohexol (Omnipaque) on renal function was investigated in diabetic patients with signs of peripheral ischaemia. Forty-six patients, 70 +/- 11 years (mean +/- SD) old, age at diabetes diagnosis 53 +/- 17 years, and with varying degrees of diabetic nephropathy were studied before 1, 2, and 30 days after aortobifemoral arteriography. Serum creatinine, creatinine clearance, urinary excretion of immunoglobulin G, albumin collagen IV (NC1), kappa and lambda chains, alpha-1 microglobulin and Tamm-Horsfall protein were evaluated. Within 1 month before and 30 days after arteriography, the glomerular filtration rate was measured by clearance of iohexol. The acute effect of the radiocontrast medium was an increase in the serum creatinine level in 41 (89%) patients, with a more than 25% increase in 12 (26%) patients. The excretion rates of immunoglobulin G and albumin decreased, whereas the proximal and distal tubular function and the excretion of collagen IV did not change. The increment in serum creatinine was associated with the preangiographic renal function (p < 0.05), a history of heart failure (p < 0.01), but not with age, duration and type of diabetes, gender, systolic or diastolic blood pressure, glycated haemoglobin (HbAlc) or blood glucose levels. The increase of serum creatinine was associated with a pre-existing proximal tubular dysfunction and a worsening of distal tubular function. No changes in the parameters measured persisted 30 days after angiography. In summary, a transient increment in serum creatinine level after arteriography occurred in 89% of diabetic patients. It was associated with the preangiographic renal function, a history of heart failure and signs of preexisting proximal tubular dysfunction and worsening of distal tubular function. However, these changes were reversible.

Age of Onset

Retinal nitro blue tetrazolium staining and catalase activity in rat models of diabetes.

BACKGROUND: Recent studies have suggested that reactive oxygen species may be involved in the development of diabetic retinopathy. METHODS: Nitro blue tetrazolium (NBT) staining, a marker of reductants which may be induced by free radicals such as superoxide, and catalase activity, as an indirect measure of hydrogen peroxide (H2O2) generation, were studied in the rat retina in three conditions known to cause diabetes-like retinopathy, i.e. rats with spontaneous diabetes (the BB Wistar rat), rats with streptozotocin-induced diabetes mellitus, and rats fed on galactose. Male Wistar BB rats were studied 4-10 weeks after diagnosis of diabetes. Streptozotocin (60 mg/kg) was injected i.p. at 8 weeks of age and the experiments were performed after 8 weeks of diabetes. Young Sprague-Dawley rats were fed a 50% galactose diet for 9, 12 or 22 months. RESULTS: In trypsinized vessel preparations, more intense NBT staining was observed only in rats fed a galactose diet for 22 months. In cross sections, the number of stained vessels were increased in BB rats (p < 0.01), but not in rats with streptozotocin-induced diabetes. Catalase activity did not differ between any of the experimental groups and their matched controls. CONCLUSIONS: Increased amount of NBT reductants in retinal vessels occurred in BB Wistar rats and to some extent in galactose-fed rats, indicating a possible role for free radicals in the development of diabetic retinopathy. There was no evidence of increased retinal H2O2 production or activation of catalase, indicating that this particular enzyme was not affected during the conditions studied.

Animals

HLA-DQB1*0201/0302 is associated with severe retinopathy in patients with IDDM.

Some insulin-dependent diabetic (IDDM) patients develop severe forms of retinopathy. Putative risk factors such as hypertension, poor metabolic control, nephropathy and growth hormone levels do not fully explain the progress of retinopathy in these patients. It has been discussed whether there is a genetic marker, since some diabetic patients without any known predisposing risk factors develop severe retinopathy and others do not. In the present study, HLA-DR and DQ were compared in two patient groups with IDDM. One group consisted of patients with early-onset diabetes, with severe non-proliferative or proliferative retinopathy; the other group had no or only mild signs of retinopathy. High resolution HLA typing was carried out by polymerase chain reaction (PCR) and hybridization with allele specific probes. Alleles on the DR3-DQ2 haplotype, DRB1*0301, DQA1*0501 and DQB1*0201, were more frequent in patients with severe retinopathy. A difference was seen when combining certain alleles in the genotypes of DQA1*03/0501 (p > 0.05) and DQB1*0201/0302 (p < 0.01). The findings of the present study suggest that DQB1*0201/0302 is the strongest genetic marker for severe retinopathy and DRB1*0301/0401 only has a secondary influence when combined with this genotype. It seems as if IDDM patients who are positive for the genotype DR3-DQ2/DR4-DQ8 (DRB1*0301-DQA1*0501-DQB1*0201/DRB1*0401 -DQA1*03-DQB1*0302) are at greater risk of developing severe retinopathy.

Adult

The prognostic value of albuminuria for the development of cardiovascular disease and retinopathy: a 5-year follow-up of 451 patients with type 2 diabetes mellitus.

The aim of the present study was to evaluate the risk for vascular morbidity or death and retinopathy in relation to urinary albumin concentration. To that end, we performed a 5-year follow-up study of all type 2 diabetic patients attending the outpatient-clinic. A total of 444 (98.4%) out of 451 adult patients initially studied were evaluated for the degree of retinopathy and levels of HbA1c blood pressure, serum creatinine and urinary albumin. Vascular morbidity and causes of death were registered by one and the most severe event only. Forty-seven patients developed atherosclerotic vascular disease, i.e. myocardial infarction (n = 19), cerebrovascular disease (n = 20), or amputation (n = 8), and 42 died. The observed annual mortality rate was 22.1/1000 compared to an expected rate of 13.6/1000 for the general population with corresponding age and sex. Urinary albumin concentration was found to be a prognostic marker for the development of vascular disease and death in patients treated with insulin at baseline (P < 0.01), whereas this was not the case in patients treated with diet and/or oral agents at baseline. However, insulin treatment per se was not associated with an increased mortality or mortality or morbidity. Urinary albumin concentration was not correlated with incidence or progression of retinopathy regardless of type of diabetes treatment. In conclusion, this study showed that albuminuria was a prognostic factor for vascular morbidity and death in type 2 diabetic patients treated with insulin but not in patients treated with diet or oral agents. Furthermore, albuminuria was not a predictor for incidence or progression of retinopathy.

Adult

Glucose levels and insulin secretion during a 75 g glucose challenge test in normal pregnancy.

OBJECTIVES: The aim of the study was to evaluate glucose levels and insulin secretion early in pregnancy and at a time when gestational diabetes mellitus frequently occurs in order to define reference values for glucose tolerance during pregnancy. The results were also related to maternal factors that might identify subjects at risk of developing gestational diabetes mellitus as well as foetal factors that might be a result of impaired glucose tolerance during pregnancy. DESIGN: A prospective study. SETTING: All Caucasian women attending one antenatal out-patient care unit were offered a 75 g oral glucose tolerance test at the 17th and 32nd week of gestation. SUBJECTS: A total of 586 consecutive pregnant women were included in the study. All 586 women were examined by repeated blood glucose measurements and 298 agreed to perform oral glucose tolerance tests as well. MAIN OUTCOME MEASURES: Venous whole blood glucose values were measured in the fasting state and in samples obtained 15, 30, 45, 60, 75, 90 and 120 min after oral intake of 75 g glucose. Serum insulin and C-peptide were also measured at these times. In all subjects, a random blood glucose sample was taken at the first visit, and thereafter at the 20th, 30th and 36th week of gestation. Information was also obtained from all subjects regarding body mass index, weight gain during pregnancy, smoking habits, family history of diabetes and hypertension, hypertension during pregnancy, past obstetric history, parity, and fetal outcome. RESULTS: The glucose tolerance was significantly impaired at the 32nd week of gestation compared with the 17th week of gestation. The mean +2SD 2 h glucose value during the oral glucose tolerance test at the 32nd week of gestation was 8.0 mmol L-1. Impaired glucose tolerance was characterised by increased insulin resistance, with a significant rise in serum insulin and C-peptide concentrations and in the insulin/glucose index during the oral glucose tolerance test at the 32nd week of gestation. Maternal factors associated with an impaired glucose tolerance were a family history of diabetes mellitus, smoking, a weight gain more than 18 kg during pregnancy, and glucosuria, while a family history of hypertension and hypertension present during pregnancy were not. Foetal factors that might be a result of impaired glucose tolerance during pregnancy, e.g. macrosomia and prematurity as well as complicated deliveries such as vacuum extraction/forceps or Caesarean section, all tended to be associated with higher blood glucose values. The same pattern was seen when the Apgar score was < 7. CONCLUSIONS: The results from this study show that the present cut-off values for diagnosis of gestational diabetes mellitus should be revised. Even if some maternal factors might indicate an increased risk for impaired glucose tolerance during pregnancy, they are probably not enough to detect women with gestational diabetes mellitus. Therefore, a screening programme for gestational diabetes should be considered.

Adult

The importance of early diagnosis of treatable diabetic retinopathy for the four-year visual outcome in older-onset diabetes mellitus.

The four-year visual outcome was retrospectively studied in patients with older-onset diabetes mellitus and diabetic retinopathy in need of laser treatment. Visual acuity in 53 patients examined by ophthalmologists who referred the patients for an evaluation of retinopathy before laser treatment, was compared to that of 47 patients examined by ophthalmologists who also performed the photocoagulation. The number of eyes that became blind (visual acuity < or = 6/60) during the four-year period was higher (23/90 vs 9/91; p < 0.01) among referred patients, whereas the number of retinal examinations per patient during the three-year period prior to laser treatment did not differ between the two groups. Among referred patients, 13% had not been ophthalmologically examined before the treatment-requiring retinopathy was found. Corresponding figure for those examined at the laser centre was 23%. Severe macular oedema in regularly examined patients was more common among referred patients (9/30 vs 1/32; p < 0.01). The results indicate that screening for diabetic retinopathy in older-onset diabetes was not performed satisfactorily. In addition, laser treatment was delayed in older-onset diabetic patients controlled by ophthalmologists who referred patients for photocoagulation, resulting in an increased incidence of legally blind eyes. The study also stresses the importance of carrying out knowledge of when and how to diagnose early sight-threatening diabetic retinopathy to ophthalmologists referring patients for laser treatment.

Age of Onset

Greater reduction of urinary albumin excretion in hypertensive type II diabetic patients with incipient nephropathy by lisinopril than by nifedipine.

A double-blind, randomised, parallel group, multicentre, multinational study compared the effects of 12 months' treatment with lisinopril (10-20 mg once daily) or nifedipine retard tablets (20-40 mg twice daily) in 239 males (aged 18-75 years) and 96 post-menopausal females (aged 40-75 years). They all had a history of clinically stable type II diabetes > 3 months, microalbuminuria and early diabetic nephropathy (a urinary albumin excretion (UAE) rate ranging from 20 to 300 micrograms/min) and a sitting diastolic blood pressure (DBP) 90-100 mm Hg (Korotkoff phase V) inclusive at both entry and after 3-4 weeks' placebo treatment. The aim of treatment was to achieve a reduction in sitting DBP to < 90 mm Hg 24-30 h after the last dose of lisinopril or 12-18 hours after the last dose of nifedipine and to evaluate the effect of these treatments on UAE over 12 months. The effect of the two treatments on ambulatory blood pressure (BP) was also evaluated in a subset of patients. Management of diabetes with oral hypoglycaemic drugs, diet and insulin alone or in combination was permitted. Median UAE fell on lisinopril from 65.5 (range 20-297) micrograms/min at baseline to 39.0 (2-510) micrograms/min after 12 months. On nifedipine median UAE fell from 63.0 (range 20-289) micrograms/min at baseline to 58.0 (9-1192) micrograms/min after 12 months. The estimated median difference between the effects of the two treatments was 20 micrograms/min (P = 0.0006). Over 12 months both treatments produced similar falls in sitting BP from 163 +/- 17/99 +/- 6 mm Hg (mean +/- s.d.) to 147 +/- 18/88 +/- 10 mm Hg for lisinopril and from 161 +/- 18/97 +/- 5 mm Hg to 150 +/- 18/88 +/- 9 mm Hg for nifedipine. Ambulatory BP was assessed in a subset of patients and using areas under the BP-time curve (AUC) a comparison of the effects of the two treatments showed no between-treatment differences. Creatinine clearance, glycaemic control (HbA1c) and lipid profiles did not change significantly during either treatment. Frequency of withdrawals and adverse events were similar for both treatments. We conclude that lisinopril has a significantly more beneficial effect on UAE than nifedipine despite similar effects on both BP and glycaemic control in type II diabetic patients with hypertension.

Adolescent

The cerebral vascular response to a rapid decrease in blood glucose to values above normal in poorly controlled type 1 (insulin-dependent) diabetes mellitus.

The effect of rapid lowering of blood glucose on cerebral blood flow (CBF) was studied in 10 Type 1 (insulin-dependent) diabetic patients (age 23.5 +/- 3.8 years; mean +/- S.D.) with longstanding, poor metabolic control (HbAlc 11.2 +/- 1.0%; normal value 4.0-5.3%) using an intravenous xenon 133 single photon emission computed tomography technique. After a fall in blood glucose, during 81 +/- 11 min (mean +/- S.E.M.), from 18.2 +/- 1.4 mmol/l to 9.2 +/- 0.9 mmol/l CBF was unchanged, but increased from its initial value of 48.8 +/- 2.9 ml/100 g per min to 57.1 +/- 2.4 ml/100 g per min (P < 0.001) when the blood glucose level was restored. The CBF was higher in the right compared to the left hemisphere at all measurements (1.8 +/- 0.5 ml/100 g per min, P < 0.01; 1.9 +/- 0.5 ml/100 g per min, P < 0.05; 2.1 +/- 0.7 ml/100 g per min, P < 0.05, respectively). The change in CBF was inversely correlated with time for fall of blood glucose, but there was no correlation with absolute levels of blood glucose. The respiratory end-tidal PCO2 decreased during the low blood glucose level, but there was no correlation between the PCO2 and CBF. The cerebral volume was unchanged during the study. The results indicate that in patients with chronic hyperglycemia a rapid fall in blood glucose may cause a rise in CBF of the same magnitude as previously shown during absolute hypoglycemia in patients with well controlled diabetes mellitus and in normal subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Decreasing incidence of major amputation in diabetic patients: a consequence of a multidisciplinary foot care team approach?

The purpose of this retrospective study was to evaluate the changes in diabetes-related lower extremity amputations following the implementation of a multidisciplinary programme for prevention and treatment of diabetic foot ulcers in a 0.2 million population with a 2.4% prevalence of diabetes. All diabetes-related primary amputations from toe to hip from 1 January 1982 to 31 December 1993 were included. In 294 diabetic patients, 387 primary major (above the ankle) or minor (through or below the ankle) amputations were performed, constituting 48% of all lower extremity amputations. The annual number of amputations at all levels decreased from 38 to 21, equalling a decrease of incidence from 19.1 to 9.4/100,000 inhabitants (p = 0.001). The incidence of major amputations decreased by 78% from 16/1 to 3.6/100,000 inhabitants (p < 0.001). The absolute number of amputations with a final level below the ankle showed no increase, but their proportion increased from 28 to 53% (p < 0.001) and the reamputation rate decreased from 36 to 22% (p < 0.05) between the first and last 3-year period. Thus, a substantial long-term decrease in the incidence of major amputations was seen as well as a decrease in the total incidence of amputations in diabetic patients. Seventy-one per cent of the amputations were precipitated by a foot ulcer. These findings indicate that a multidisciplinary approach plays an important role to reduce and maintain a low incidence of major amputations in diabetic patients.

Adult

Clinical characteristics in relation to final amputation level in diabetic patients with foot ulcers: a prospective study of healing below or above the ankle in 187 patients.

The aim of this study was to describe the clinical characteristics in relation to final amputation level in diabetic patients with foot ulcers. In a prospective series, 187 consecutively presenting patients were investigated. From admission until final outcome, the patients were treated by a multidisciplinary team both as in- and out-patients. All the patients had one or more signs of neuropathy and 171 had evidence of peripheral vascular disease. Healing with an amputation below the ankle occurred in 74 patients, 88 patients healed with an amputation above the ankle, and 25 patients died unhealed. Amputation above the ankle was associated with high age, living in an institution, a limited walking capacity, cerebrovascular disease, congestive heart failure, and a low hemoglobin level. Amputation below the ankle was associated with diabetes diagnosis before 30 years of age and diabetes duration. In conclusion, older age, history of cerebrovascular disease and low hemoglobin level are associated with above ankle amputation level in diabetic patients with foot ulcers. However, level selection cannot be based upon these factors only, since some patients at high age, with cerebrovascular disease or with a low hemoglobin value, healed with an amputation below the ankle. None of these factors per se should be taken as a cause to choose a primary amputation above the ankle, unless amputation is supported by the total clinical picture, including local characteristics, such as type and localization of ulcer, and signs of peripheral vascular disease. More attention should be paid to biological than to chronological age.

Adult

Plasma beta-hexosaminidase isoenzymes A and B exhibit different relations to blood glucose levels in a population of Type 1 diabetic patients.

The activity of lysosomal enzymes, such as beta-hexosaminidase (Hex), is increased in the plasma and serum of diabetic patients. A positive association has been shown between enzyme activity and glycated proteins, indicating an association with the degree of metabolic control. Several isoenzymes of Hex exist. Studies have reported different proportions of the isoenzymes in plasma from diabetic patients, compared with healthy subjects. In the present study, Hex isoenzymes were examined in 76 Type 1 diabetic patients, of mean age 37.4 years (SD 12.9) compared with 38 age- and sex-matched healthy control subjects in an attempt to evaluate the influence of long- and short-term changes in blood glucose levels on these isoenzymes. The results show that Hex A activity (p<0.01), but not Hex B activity, was higher in the diabetic patients. Hex A activity was positively associated with both the actual blood glucose levels (r = 0.48, p<0.001) and haemoglobin A1c (HbA1c) (r = 0.43, p<0.001), while Hex B activity was associated with the level of HbA1c only (r = 0.42, p<0.001). Both Hex A and B activities were also positively associated with early signs of diabetic nephropathy (e.g. urinary excretion of Hex, fractional albumin excretion ratio and urinary albumin). There was no association between Hex A and B activities and different degrees of retinopathy. In conclusion, the present study demonstrates an association between Hex A and B and metabolic parameters in diabetes as well as with clinical signs of early diabetic nephropathy, but no association with the degree of retinopathy. Furthermore, Hex A seems to be more influenced than Hex B by short-term changes in blood glucose levels.

Adult

Increased catalase levels and hypoxanthine-enhanced nitro-blue tetrazolium staining in rat retina after ischemia followed by recirculation.

In the present study, using retinal ischemia as a model, we examined if different periods of ischemia and recirculation influenced the generation of reactive oxygen species, i.e. in hydrogen peroxide generation and nitroblue tetrazolium (NBT) reduction. Ischemia was induced for 30 and 90 min by ligation of the optic nerve with the vessels and recirculation was established by removing the ligature. The rats were sacrificed after 15 min or 3 days of recirculation. The retinas were separated from the pigment epithelium for measurements of catalase activity and examination of NBT staining. Compared to controls, the catalase activity was increased after 30 and 90 min of ischemia followed by 15 min of recirculation, and after 90 min of ischemia followed by 3 days of recirculation. As in controls, NBT staining was observed, both after 30 and 90 min of ischemia followed by 15 min of recirculation, in photoreceptors, in both plexiform layers, in some ganglion and glial cells, and, occasionally, in cells in the inner nuclear layer. Opposite to controls, addition of hypoxanthine to the NBT solution resulted in an increased staining in vessels in the inner nuclear layer in retinas subjected to 30 min of ischemia followed by 3 days of recirculation. The increased catalase activity suggests an increased amount of this free radical scavenger after ischemia followed by short-term and long-term recirculation. The hypoxanthine-enhanced NBT staining of blood vessel walls after ischemia followed by long-term recirculation indicates an activation of xanthine oxidase and an increased production of NBT reductants, some of which may represent oxygen free radicals.

Animals

Nitro blue tetrazolium staining and hydrogen peroxide production in the rat retina in vitamin E deficiency and after light exposure.

Nitro blue tetrazolium (NBT) staining in normal rat retina was previously found to be affected by inhibition of free radical-related enzyme systems, indicating that NBT might be useful as a marker of free radicals. The aim of the present study was to investigate NBT staining in rat retina in vitamin E deficiency and after blue light exposure, and also to measure hydrogen peroxide (H2O2) production indirectly by measuring catalase activity under these conditions. Vitamin E deficiency resulted in morphological changes in the retina and increased NBT staining in the photoreceptors and in the outer plexiform layer. Light exposure caused increased staining in the inner segments of photoreceptors. The increased staining was not clearly influenced by addition of the free radical scavengers superoxide dismutase and catalase. The catalase activity was not influenced by light exposure, while it was increased in vitamin E-deficient retina compared to controls. The results indicate that reducing systems as measured by NBT were activated in the retina under these conditions. However, to what extent the reductants represent free radicals still has to be established using other methods.

Animals

Influence of intensified insulin regimen on quality of life and metabolic control in insulin-dependent diabetes mellitus.

Seventy-eight non-randomized patients with IDDM, aged 33.8 +/- 9.6 years (mean +/- S.D.), with a duration of diabetes of 16.6 +/- 9.5 years and a HbA1c level of 8.0% +/- 1.5 at baseline were included in the study. The effects of a change from a 3-dose insulin regimen using conventional syringes to a treatment mode using 4 injections per day with a pen injector on metabolic control, perceived distress from diabetes on everyday life and correspondence between expectations and experiences of treatment during a 1-year trial were assessed. The experience measures were registered at baseline and after 3 and 12 months, respectively. HbA1c levels were measured every 3 months. Neither the metabolic control nor the body mass index or rate of hypoglycemic episodes changed during the study period. However, the patients experienced a decreased distress from diabetes, which appeared during the first 3 months and remained unchanged thereafter. The expectations of advantages from the intensified insulin therapy were generally high and were mostly either fulfilled or exceeded by experiences. We conclude that multiple insulin injection therapy, under routine treatment conditions, is subjectively preferable to patients and has favourable effects on their quality of life although something more is required in order to also achieve an improvement of metabolic control.

Adult

A 5-year follow-up study on the incidence of retinopathy in type 1 diabetes mellitus in relation to medical risk indicators.

OBJECTIVES: The aim of the present study was to describe the 5-year incidence of retinopathy in type 1 diabetes mellitus and to characterize risk indicators for the development and progression of retinopathy. DESIGN: A cross-sectional study of type 1 diabetic patients taken care of at a medical department. SETTING: All type 1 diabetic patients attending the Department of Internal Medicine, University Hospital, Lund, during a 2-year period were offered ophthalmological examination. SUBJECTS: A total of 396 out of 461 (85.9%) initially examined type 1 diabetic patients formed the basis for this 5-year follow-up study. MAIN OUTCOME MEASURES: The degree of retinopathy was based on fundus photography or biomicroscopy. Degree of metabolic control was assessed by HbA1c levels, signs of nephropathy by albumin creatinine clearance ratio and urinary albumin levels. Blood pressure was measured in the supine position. Duration of diabetes, age, and insulin dosage were registered. RESULTS: The incidence of retinopathy was 47.2% and progression from background to severe retinopathy occurred in 41%. Risk indicators for the development of retinopathy were duration of diabetes (P < 0.001), degree of metabolic control (P < 0.001), insulin dosage (P < 0.05) and signs of nephropathy based on measurements of albumin creatinine clearance ratio (P < 0.01) and urinary albumin concentration (P < 0.05). Two risk indicators could be identified for progression of retinopathy, i.e. the degree of metabolic control (P < 0.01) and diastolic blood pressure (P < 0.05). CONCLUSIONS: The results suggest that apart from poor metabolic control, development of retinopathy in type 1 diabetes is associated with long diabetes duration and clinical signs of diabetic nephropathy. Progression of retinopathy is associated with poor metabolic control and elevated diastolic blood pressure levels.

Adult