| 1. |
- Agardh, Carl David, et al.
(author)
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Effects of inhibition of glycation and oxidative stress on the development of diabetic nephropathy in rats.
- 2002
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In: Journal of Diabetes and its Complications. - 1873-460X. ; 16:6, s. 395-400
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Journal article (peer-reviewed)abstract
- We investigated whether aminoguanidine (AG), an inhibitor of advanced glycated end product formation, or probucol (PB), a free radical scavenger, could influence signs of glomerular and distal tubular function and morphological changes in kidneys of male Wistar rats after 6 months of streptozocin (STZ)-induced diabetes. Diabetic rats had a higher kidney weight/body weight ratio (P<.001), but neither AG nor PB influenced the increased ratio. Diabetes caused an increased urinary albumin excretion (P<.05), which was normalized by AG, but further exaggerated by PB (P<.001). Diabetes also caused an increase in the urinary excretion of Tamm–Horsfall protein (P<.001). Both AG and PB attenuated this increase (P<.05 for both). A few glomeruli displayed focal thickening of varying degrees. Silver staining disclosed the glomerulopathy to be intercapillary glomerulosclerosis. Rats on PB-enriched diet displayed less pronounced changes than untreated rats (P<.01), while AG had no effect. The results suggest that oxidative stress could be involved in the development of diabetic nephropathy.
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| 2. |
- Agardh, Carl-David, et al.
(author)
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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
- 1997
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In: Diabetes Research and Clinical Practice. - 1872-8227. ; 35:2-3, s. 113-121
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Journal article (peer-reviewed)abstract
- 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.
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| 3. |
- Agardh, Carl-David, et al.
(author)
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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
- 1996
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In: Diabetes Research and Clinical Practice. - : Elsevier BV. - 1872-8227 .- 0168-8227. ; 32:1-2, s. 35-44
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Journal article (peer-reviewed)abstract
- 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.
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| 4. |
- 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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| 5. |
- 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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| 6. |
- Agardh, Elisabet, et al.
(author)
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Putative risk factors associated with retinopathy in patients with diabetes diagnosed at or after 30 years of age
- 1989
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In: Diabetic Medicine. - 1464-5491. ; 6:8, s. 724-727
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Journal article (peer-reviewed)abstract
- In a cross-sectional study of diabetic patients diagnosed at or after 30 years, and with different stages of retinopathy, factors such as duration of diabetes, treatment mode, metabolic control, blood pressure, and clinical signs of nephropathy were examined. The different stages of retinopathy used were absence of retinopathy, simplex, and severe retinopathy. Patients with simplex and severe retinopathy were older than those without retinopathy (p less than 0.001, and p less than 0.01, respectively). They also had a longer duration of diabetes (p less than 0.001), and were more often treated with insulin (p less than 0.001) and in larger doses (p less than 0.001). Their glycosylated haemoglobin levels were higher (p less than 0.01). Their systolic blood pressure was higher (p less than 0.01), but the diastolic blood pressure did not differ, and the number of patients treated for hypertension was similar in all groups. Albumin clearance was higher (p less than 0.01 and p less than 0.001), as were urinary albumin levels (p less than 0.001). The only variables that distinguished patients with simplex from those with severe retinopathy were albumin clearance (p less than 0.01) and urinary albumin levels (p less than 0.05).
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| 7. |
- Agardh, Elisabet, et al.
(author)
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The prevalence of retinopathy and associated medical risk factors in type I (insulin-dependent) diabetes mellitus
- 1989
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In: Journal of Internal Medicine. - 1365-2796. ; 226:1, s. 47-52
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Journal article (peer-reviewed)abstract
- The prevalence of diabetic retinopathy and the associated medical risk factors, such as age at onset and duration of diabetes, metabolic control, blood pressure, albumin clearance and serum creatinine, were studied in 501 patients with type I diabetes mellitus. The prevalence of retinopathy, characterized as simplex, maculopathy, preproliferative, and proliferative, was 60.5%. Patients with retinopathy were younger at the onset of diabetes, and had a longer duration of disease. In patients with more than 10 years of diabetes, proliferative retinopathy was more frequent if onset was before they were 15 years old, despite the fact that the duration of diabetes did not differ. Patients with severe retinopathy had worse metabolic control, and were more frequently treated for hypertension. In addition, the systolic blood pressure was elevated in all groups of patients with any type of retinopathy, whereas the diastolic blood pressure was elevated only in patients with more severe forms. Patients with severe retinopathy also had higher levels of albumin clearance.
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| 8. |
- Lövestam Adrian, Monica, et al.
(author)
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Diabetic retinopathy, visual acuity, and medical risk indicators: a continuous 10-year follow-up study in Type 1 diabetic patients under routine care
- 2001
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In: Journal of Diabetes and its Complications. - 1873-460X. ; 15:6, s. 287-294
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Journal article (peer-reviewed)abstract
- 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.
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| 9. |
- Lövestam-Adrian, Monica, et al.
(author)
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Type 1 diabetes patients with severe non-proliferative retinopathy may benefit from panretinal photocoagulation.
- 2003
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In: Acta Ophthalmologica Scandinavica. - : Wiley. - 1395-3907. ; 81:3, s. 221-225
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Journal article (peer-reviewed)abstract
- Purpose: To examine whether panretinal photocoagulation for severe non-proliferative retinopathy in type 1 diabetes patients could halt the progression of retinopathy with subsequent vitreous haemorrhages and visual impairment. Methods: During a 10-year follow-up study period of 344 type 1 diabetes patients, 81 subjects went through panretinal photocoagulation. Forty patients were treated for severe non-proliferative retinopathy (age at onset of diabetes 14 ± 8 years, diabetes duration 18 + 10 years) and 41 for proliferative retinopathy (age at onset 15 ± 10 years, diabetes duration 22 + 13 years). One randomly selected eye per patient forms the basis for the study. Metabolic control, systolic and diastolic blood pressure, serum creatinine and urinary albumin levels were measured and analysed yearly during the follow-up period. Results: A total of 35% (14/40) of eyes treated for severe non-proliferative retinopathy developed neovascularizations during a mean time of 2.9 ± 1.5 years. Vitreous haemorrhages were more frequent in eyes with proliferative retinopathy at treatment than in eyes with severe non-proliferative retinopathy (12/41 versus 2/40; p = 0.007). The number of vitrectomies due to vitreous haemorrhages in eyes treated for severe non-proliferative retinopathy tended to be lower (1/40 versus 6/41; p = 0.052). Before photocoagulation, visual acuity (VA) was similar in eyes with severe non-proliferative retinopathy and in those with proliferative retinopathy (1.0, 0.4-1.0 versus 1.0, 0.1-1.0; median and range). Visual impairment and blindness tended to develop more often in eyes treated for proliferative retinopathy compared to those treated for severe non-proliferative retinopathy (10/40 versus 4/40; p = 0.056). Eyes with neovascularizations at follow-up were more often visually impaired (VA < 0.5) than eyes without neovascularizations (15/55 versus 1/26; p = 0.016). Conclusion: In type 1 diabetes, panretinal photocoagulation may be beneficial even at the severe non-proliferative retinopathy stage in terms of preventing vitreous haemorrhage, subsequent vitrectomy and visual impairment.
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| 10. |
- Torffvit, Ole, et al.
(author)
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Albuminuria and associated medical risk factors: a cross-sectional study in 451 type II (noninsulin-dependent) diabetic patients. Part 2
- 1991
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In: Journal of Diabetic Complications. - 0891-6632. ; 5:1, s. 29-34
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Journal article (peer-reviewed)abstract
- The association between urinary albumin concentration (UAC) in a morning urine sample and medical risk factors was evaluated in a cross-sectional study of 451 type II (noninsulin-dependent) diabetic patients. The following four groups of patients were created according to their urinary albumin levels: A) normal (less than 12.5 mg/L); B) high normal (12.5-30 mg/L); C) microalbuminuria, ie, incipient nephropathy (31-299 mg/L); and D) clinical nephropathy (greater than or equal to 300 mg/L). The patients with high normal levels had higher HbA1c and systolic blood pressure levels than patients with values within normal limits. The prevalence of incipient and clinical diabetic nephropathy was 20 and 7%, respectively. Incipient nephropathy was associated with higher blood pressures and body weights. Patients with clinical nephropathy had even further increases in these parameters, were older, and had longer duration of diabetes. In both groups of nephropathy, men were preponderant. Thirty six percent of all patients and 73% of patients with clinical nephropathy were treated for hypertension; 55% were treated with insulin. The insulin-treated patients had poorer metabolic control, but there were no differences in blood pressure or serum creatinine levels as compared with those of patients not receiving insulin treatment. The proportion of patients with severe retinopathy increased with the degree of albuminuria, although 22% of the patients with clinical nephropathy continued to be nonretinopathic.
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