| 1. |
- Agardh, Carl-David, et al.
(author)
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Association between urinary N-acetyl-beta-glucosaminidase and its isoenzyme patterns and microangiopathy in type 1 diabetes mellitus
- 1991
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In: Clinical Chemistry. - 0009-9147. ; 37:10 Pt 1, s. 1696-1699
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Journal article (peer-reviewed)abstract
- Urinary N-acetyl-beta-glucosaminidase (NAG) and its isoenzymes (NAG A and NAG B) in samples from 87 type 1 diabetic patients and 40 apparently healthy reference subjects were studied with enzyme immunoassays. The diabetic patients had higher concentrations of urinary NAG than did the control subjects (P less than 0.01), but the isoenzyme pattern did not differ. There was a positive correlation between metabolic control (Hb A1c concentrations) and total NAG (P less than 0.01), NAG A (P less than 0.01), and NAG B (P less than 0.001). The diabetic patients were divided into three groups, depending on the degree of retinopathy. Subjects with severe forms of retinopathy did not have increased concentrations of urinary NAG unless they had concomitant nephropathy. The isoenzyme pattern was similar irrespective of degree of retinopathy or nephropathy. The results indicate that concentrations of urinary NAG are positively correlated to the degree of nephropathy, whereas there is no such correlation to the degree of retinopathy.
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| 2. |
- Agardh, Carl-David
(author)
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Diabetesnefropati
- 1992
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In: Nordisk medicin. - 0029-1420. ; 107:8-9, s. 215-216
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Journal article (peer-reviewed)abstract
- Diabetic nephropathy is a common complication in diabetes mellitus. In addition to the risk of renal failure, patients with established nephropathy are at increased risk of proliferative retinopathy and cardiovascular disease. As the earliest prodrome of nephropathy is microalbuminuria, albumin excretion needs to be monitored with a reliable method in all diabetics. In the event of microalbuminuria, diabetes treatment needs to be intensified to optimise metabolic regulation. Early institution of antihypertensive treatment is essential to avoid progression to clinical nephropathy.
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| 3. |
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| 4. |
- Agardh, Carl-David, et al.
(author)
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Free radical production and ischemic brain damage: influence of postischemic oxygen tension
- 1991
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In: International Journal of Developmental Neuroscience. - : Wiley. - 1873-474X .- 0736-5748. ; 9:2, s. 127-138
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Journal article (peer-reviewed)abstract
- It is now becoming increasingly clear that free radicals contribute to brain damage in several conditions, such as hyperoxia and trauma. It has been more difficult to prove that free radical production mediates ischemic brain damage, but it has often been suggested that it may be a major contributor to reperfusion damage, observed following transient ischemia. Recent results demonstrate that cerebral ischemia of long duration, particularly when followed by reperfusion, leads to enhanced production of partially reduced oxygen species, notably hydrogen peroxide (H2O2). It has also been suggested that postischemic hyperoxia, e.g. an increased oxygen tension during the recirculation period, adversely affects recovery following transient ischemia. Other data support the notion that brain damage caused by permanent ischemia (stroke) is significantly influenced by production of free radicals. The present study, however, fails to show that recirculation following brief periods of ischemia (15 min) leads to an enhanced H2O2 production, and that hyperoxia aggravates the ischemic damage. This study was undertaken to reveal whether variations in oxygen supply in the postischemic period following forebrain ischemia in rats affect free radical production and the brain damage incurred. To that end, rats ventilated on N2O/O2 (70:30) were subjected to 15 min of transient ischemia. Normoxic animals were ventilated with the N2O/O2 mixture, hyperoxic animals with 100% O2, and hypoxic ones with about 10% O2 (balance either N2O/N2 or N2) during the recirculation. At the end of this period, the animals were decapitated for assessment of H2O2 production with the aminotriazole/catalase method. This method is based on the notion that aminotriazole interacts with H2O2 to inactivate catalase; thus, the rate of inactivation of catalase in aminotriazole treated animals reflects H2O2 production. In a parallel series, animals ventilated with one of the three gas mixtures in the early recirculation period, respectively, were allowed to recover for 7 days, with subsequent perfusion-fixation of brain tissues and light microscopical evaluation of the brain damage. Animals given aminotriazole, whether rendered ischemic or not, showed a reduced tissue catalase activity, reflecting H2O2 production in the brain. Hyperoxic animals failed to show increased tissue H2O2 production, while hypoxic ones showed a tendency towards decreased production. However, all three groups (hypo, normo- and hyperoxic) had similar density and distribution of neuronal damage. These results suggest that although postischemic oxygen tensions may determine the rates of H2O2 production, variations in oxygen tensions do not influence the final brain damage incurred. In conclusion, there was thus no indication that variations in the postischemic oxygen supply altered production of free radicals, or modulated the damage incurred as a result of the ischemia. We conclude that free radical production may not be an important factor in the pathogenesis of brain damage following brief periods of ischemia, but may represent an important modulator following longer periods of ischemia, when a vascular component becomes an important factor in the pathological events.
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| 5. |
- Agardh, Carl-David, et al.
(author)
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Growth hormone levels in the basal state and after thyrotropin-releasing hormone stimulation in young type 1 (insulin-dependent) diabetic patients with severe retinopathy
- 1992
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In: Diabetes Research (Edinburgh, Scotland). - 0265-5985. ; 19:2, s. 81-85
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Journal article (peer-reviewed)abstract
- Sixteen young patients with type 1 diabetes mellitus and rapidly progressive severe retinopathy were examined regarding serum levels of growth hormone before and after the i.v. administration of 200 micrograms thyrotropin-releasing hormone (TRH). Serum IGF I, HbA1c, blood pressure, urinary albumin, and serum creatinine levels were also measured. The control group consisted of type 1 diabetic patients matched for age, duration of diabetes and metabolic control with no or minimal background retinopathy. The results show that basal growth hormone levels were above normal in both groups, and that there was a paradoxical increment in growth hormone levels after TRH stimulation (p < 0.05) in patients with severe retinopathy, but the values did not differ from patients with background retinopathy. IGD I levels were normal in all patients but one, and no differences were seen between the two groups. HbA1c, serum creatine, blood pressure, and urinary albumin levels were similar in the groups but patients with severe retinopathy were treated with more insulin (p < 0.001). Thus, neither abnormal growth hormone levels, nor IGF I, seems to be associated with the development of severe retinopathy in young type 1 diabetic patients.
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| 6. |
- Agardh, Carl-David, et al.
(author)
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Irreversible progression of severe retinopathy in young type I insulin-dependent diabetes mellitus patients after improved metabolic control
- 1992
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In: Journal of Diabetes and its Complications. - 1873-460X. ; 6:2, s. 96-100
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Journal article (peer-reviewed)abstract
- The impact of metabolic control on the development of rapidly progressive severe retinopathy was studied in 14 young type I insulin-dependent diabetes mellitus (IDDM) patients. Glycosylated hemoglobin (HbAlc) levels 45 months prior to and 12 months after the diagnosis of retinopathy were compared with HbAlc levels in 17 type I IDDM patients with no or minimal background retinopathy, matched for age and duration of diabetes. HbAlc levels were generally higher in patients with severe retinopathy (p less than 0.05) from 39 months until 6 months before the diagnosis of retinopathy. Thereafter, there was a gradual decrease in HbAlc levels reaching the same level as in control patients 6 months after diagnosis of retinopathy. Patients with severe retinopathy required higher doses of insulin prior to the diagnosis of retinopathy (p less than 0.05), but the insulin requirement decreased, and 12 months afterward, the insulin dosage was similar to patients with background retinopathy. Systolic blood pressure levels were slightly increased and higher in patients with severe retinopathy compared with control patients from 18 months before to diagnosis of retinopathy (p less than 0.05). Diastolic blood pressure levels likewise differed at 18 and 12 months before and at the time of diagnosis of retinopathy as well as 12 months afterward (p less than 0.05); however, no differences were seen in urinary albumin or serum creatinine levels between the groups. Thus, years of poor metabolic control, drastically improved, preceded the development of irreversible severe retinopathy in these young type I IDDM patients.
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| 7. |
- Agardh, Carl-David, et al.
(author)
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Lack of association between plasma homocysteine levels and microangiopathy in type 1 diabetes mellitus
- 1994
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In: Scandinavian Journal of Clinical & Laboratory Investigation. - : Informa UK Limited. - 1502-7686 .- 0036-5513. ; 54:8, s. 637-641
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Journal article (peer-reviewed)abstract
- The reactive vascular-injuring amino acid homocysteine was previously shown to be increased in plasma in diabetic patients with clinical signs of nephropathy. In this study, plasma homocysteine was measured in type 1 diabetic patients with normoalbuminuria (n = 22), microalbuminuria (n = 40) and proteinuria (n = 14) in order to investigate whether plasma homocysteine levels are increased already at the stage of incipient nephropathy, i.e. microalbuminuria. Furthermore, patients were characterized according to the degree of retinopathy. Plasma homocysteine in the whole population (n = 76) was related to B-Folate (r = 0.38, p < 0.01), S-Creatinine (r = 0.55, p < 0.001), S-Urea (r = 0.37, p < 0.01), U-Albumin (r = 0.46, p < 0.001), urinary N-acetyl-beta- glucosaminidase (r = 0.40, p < 0.001), systolic blood pressure (r = 0.36, p < 0.01) and diabetes duration (r = 0.44, p < 0.001). There were no differences in plasma homocysteine levels between patients with normoalbuminuria (8.0 +/- 1.7 mumol l-1; mean +/- SD) and those with microalbuminuria (9.1 +/- 3.4 mumol l-1). However, patients with clinical signs of nephropathy had higher plasma homocysteine levels (12.9 +/- 5.7 mumol l-1, p < 0.01) compared to the other two groups. There was no association between plasma homocysteine levels and different degrees of retinopathy. Thus, the present study does not show any relation between plasma homocysteine levels and early stages of diabetic nephropathy or retinopathy indicating that elevated concentrations of plasma homocysteine does not explain the increased risk for atherosclerosis observed in patients with microalbuminuria.
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| 8. |
- Agardh, Carl-David, et al.
(author)
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The influence of hypothermia on hypoglycemia-induced brain damage in the rat
- 1992
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In: Acta Neuropathologica. - 1432-0533. ; 83:4, s. 379-385
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Journal article (peer-reviewed)abstract
- The effects of hypothermia on hypoglycemic brain damage were studied in rats after a 30-min period of hypoglycemic coma, defined as cessation of spontaneous EEG activity. The rats were either normothermic (37 degrees C) or moderately hypothermic (33 degrees C). Morphological brain damage was evaluated after various periods of recovery. Hypothermic animals with halothane anesthesia never resumed spontaneous respiration, thus requiring artificial ventilation during recovery (maximally 8 h). In contrast, when isoflurane was used as the anesthetic agent, all animals survived and were examined after 1 week of recovery. There was a tendency towards gradually higher arterial plasma glucose levels during hypoglycemia with lower body temperature. The time period from insulin injection until isoelectric EEG appeared was gradually prolonged by hypothermia, and was shorter when isoflurane was used for anesthesia. Brain damage was examined within the neocortex, caudoputamen and hippocampus (CA1, subiculum and the tip of the dentate gyrus). Damage to neurons was found to be of two types, namely condensed dark purple neurons (pre-acidophilic) and shrunken bright red-staining neurons (acidophilic). In the neocortex, no clear influence of temperature on the degree of injury was seen. In the caudoputamen, the number of injured neurons clearly decreased at lower temperature (33 degrees C, P less than 0.001) when halothane was used, while no such difference was seen when isoflurane was used as the anesthetic agent. Likewise, a protective effect of hypothermia was seen in subiculum (P less than 0.01) when halothane, but not isoflurane was used.(ABSTRACT TRUNCATED AT 250 WORDS)
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| 9. |
- Agardh, Elisabet, et al.
(author)
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A 5-year follow-up study on the incidence of retinopathy in type 1 diabetes mellitus in relation to medical risk indicators
- 1994
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In: Journal of Internal Medicine. - 1365-2796. ; 235:4, s. 353-358
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Journal article (peer-reviewed)abstract
- 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.
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| 10. |
- Agardh, Elisabet, et al.
(author)
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A four-year follow-up study on the incidence of diabetic retinopathy in older onset diabetes mellitus
- 1994
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In: Diabetic Medicine. - 1464-5491. ; 11:3, s. 273-278
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Journal article (peer-reviewed)abstract
- Out of 369 diabetic patients with an age at onset of diabetes > or = 30 years previously studied, 325 (88%) were included in an ophthalmological follow-up examination 4 years later. In patients treated with oral drugs at baseline, the incidence of any type of retinopathy was 30.8% and of severe retinopathy 5.7%. All patients who developed severe retinopathy received insulin during the follow-up period. At baseline, duration of diabetes, diastolic blood pressure, and signs of nephropathy (p < 0.05 in all cases) as well as degree of metabolic control (p < 0.01) differed between patients who developed retinopathy and those who did not. At follow-up, there were no longer any differences regarding degree of metabolic control and diastolic blood pressure. In patients treated with insulin at baseline, the incidence of any type of retinopathy was 41.0% and of severe retinopathy 16.1%. At baseline, duration of diabetes (p < 0.01), degree of metabolic control, and insulin dosage (p < 0.05 in both cases) differed between patients who developed retinopathy and those who did not. At follow-up, there was no longer any difference in insulin dosage.
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