| 1. |
- Agardh, Carl David, et al.
(författare)
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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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Ingår i: Journal of Diabetes and its Complications. - 1873-460X. ; 16:6, s. 395-400
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Tidskriftsartikel (refereegranskat)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.
(författare)
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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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Ingår i: Diabetes Research and Clinical Practice. - 1872-8227. ; 35:2-3, s. 113-121
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Tidskriftsartikel (refereegranskat)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.
(författare)
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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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Ingår i: Diabetes Research and Clinical Practice. - : Elsevier BV. - 1872-8227 .- 0168-8227. ; 32:1-2, s. 35-44
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Tidskriftsartikel (refereegranskat)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.
(författare)
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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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Ingår i: Journal of Internal Medicine. - 1365-2796. ; 235:4, s. 353-358
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Tidskriftsartikel (refereegranskat)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.
(författare)
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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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Ingår i: Diabetic Medicine. - 1464-5491. ; 11:3, s. 273-278
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Tidskriftsartikel (refereegranskat)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.
(författare)
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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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Ingår i: Diabetic Medicine. - 1464-5491. ; 6:8, s. 724-727
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Tidskriftsartikel (refereegranskat)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.
(författare)
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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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Ingår i: Journal of Internal Medicine. - 1365-2796. ; 226:1, s. 47-52
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Tidskriftsartikel (refereegranskat)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. |
- Bakoush, Omran, et al.
(författare)
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High proteinuria selectivity index based upon IgM is a strong predictor of poor renal survival in glomerular diseases
- 2001
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Ingår i: Nephrology Dialysis Transplantation. - : Oxford University Press (OUP). - 1460-2385 .- 0931-0509. ; 16:7, s. 1357-1363
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The transport of large proteins across the glomerular capillary wall (GCW) may increase several fold in glomerular diseases. The occurrence of IgM in urine is a consequence of the presence of large defects or shunts in the GCW, whereas albuminuria is probably a result of an altered charge- and size-selectivity of the GCW. In order to examine whether patho-morphological differences influence the renal outcome in proteinuric glomerulopathies, we examined urinary excretion of IgM and albumin as prognostic markers of glomerular disease. METHODS: An observational study over a median of 41 (+/-3) months was conducted in 84 patients with biopsy-verified glomerular disease. The patients were subdivided into groups with low (< or =0.002) and high (>0.002) proteinuria selectivity index based upon IgM (IgM-SI), and into groups with low (< or =200 mg/mmol) and high (>200 mg/mmol) albumin creatinine index (ACI). RESULTS: In the high IgM-SI group, the median creatinine clearance (Ccr) decreased by 26%, and 62% of the patients decreased in Ccr by >5 ml/ min/year during the follow-up time. In comparison, the median Ccr decreased by 8% in the low IgM-SI group (P<0.001) and only 18% of the patients in this group deteriorated by >5 ml/min/year in the Ccr. Eleven (21%) of the 51 patients in the high IgM-SI group developed end-stage renal failure compared with none of the 33 patients in the low IgM-SI group. All the patients that progressed to uraemia had decreased Ccr (<60 ml/min) at entry into the study. However, among all these patients, only those with high IgM-SI, and none with low IgM-SI, developed end stage renal failure. The fall in Ccr did not differ significantly between the patients in high (12%) and low (16%) ACI groups. CONCLUSION: The results of this study indicate that an increased IgM-SI value is a stronger predictor of clinical outcome in proteinuric glomerulopathies than baseline albuminuria. This finding may reflect different patho-histological mechanisms influencing renal survival in glomerular diseases.
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| 9. |
- Bakoush, Omran, et al.
(författare)
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Higher urinary IgM excretion in type 2 diabetic nephropathy compared to type 1 diabetic nephropathy.
- 2002
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Ingår i: Kidney International. - : Elsevier BV. - 1523-1755 .- 0085-2538. ; 61:1, s. 203-208
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Proteinuria, due to impairment of the charge- and/or size selectivity of the glomerular capillary wall (GCW) is the earliest clinical evidence of diabetic nephropathy (DN). To study the pathophysiological differences between patients with DN in type 1 diabetes mellitus (type 1 DN) and type 2 diabetes mellitus (type 2 DN), we compared the patterns of urinary proteins of different size and charge in the two entities of diabetic kidney disease. METHODS: Urine concentrations of albumin, IgG2, IgG4 and IgM were assessed in 22 (15 males and 7 females) patients with type 1 DN, and in 20 (18 males and 2 females) patients with type 2 DN. Comparisons with one control group of 13 (12 males and one female) patients with nephrosclerosis due to systemic hypertension and a second control group of 16 (14 males and 2 females) healthy controls were made. RESULTS: The urine excretion of IgG2 and IgM and the ratio of IgG2 to IgG4 (IgG2/IgG4), were significantly higher in type 2 DN compared to type 1 DN (P < 0.01). Patients with type 2 DN and patients with nephrosclerosis had significantly higher urine excretion of IgG and IgM compared to the age-matched healthy subjects (P < 0.001). The IgG2/IgG4 ratio was higher in type 2 DN compared to nephrosclerosis and healthy controls (P < 0.01). CONCLUSION: The increased urine excretion of IgG and IgM that accompanies albuminuria in type 2 DN suggests that the dominant pathophysiological mechanism of proteinuria in type 2 DN might be an alteration of the size selective properties of the glomerular capillary wall, including the occurrence of non-discriminatory "shunt pathways." The charge selective properties of the glomerular capillary wall seem to be intact in type 2 DN, as indicated by the high IgG2/IgG4 ratio. The mechanisms of proteinuria in type 1 DN seem to be merely a consequence of an impaired charge selectivity of the glomerular capillary wall.
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| 10. |
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| 11. |
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| 12. |
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| 13. |
- Dash, R, et al.
(författare)
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How to predict nephropathy in type 1 diabetic patients - Routine data or provocation by exercise testing?
- 2003
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Ingår i: Scandinavian Journal of Urology and Nephrology. - : Informa UK Limited. - 0036-5599 .- 1651-2065. ; 37:5, s. 437-442
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Do exaggerated increases in blood pressure and albuminuria during exercise occur earlier than microalbuminuria and which type of test is most predictive of diabetic nephropathy? Material and Methods: A total of 33 insulin-dependent normoalbuminuric men (mean duration of diabetes 14 years; mean age 28 years) and 34 age-matched apparently healthy control subjects were studied. Urinary albumin excretion, heart rate and blood pressure were measured during fixed workload (150 W) and fixed heart rate (155 beats/min) tests. Mean follow-up time was 13.1 +/- 3.2 years. A urinary albumin level in early-morning urine persistently >30 mg/l was considered a sign of diabetic nephropathy. Results: Sixteen patients reached the endpoints of the study. Eleven had developed microalbuminuria and five macroalbuminuria (persistent levels of urinary albumin >300 mg/l). Of the latter patients, two needed dialysis. Systolic blood pressure and albumin excretion during the fixed heart rate test were higher in diabetic patients who developed signs of nephropathy than in control subjects and diabetic subjects with persistent healthy kidneys. Such differences were not found in the fixed workload test. There were no differences in glycated haemoglobin, blood pressure levels or albumin excretion at baseline between the two diabetic groups. Conclusions: To predict the development of diabetic nephropathy it seems important to choose a fixed heart rate test. High levels of systolic blood pressure in such a test were associated with the development of micro- and macroalbuminuria.
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| 14. |
- Ekelund, Ulf, et al.
(författare)
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Effektiviserad utredning möjlig vid misstänkt akut koronart syndrom. Nya undersökningsmetoder kan ge bättre vårdkvalitet och spara resurser
- 2005
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Ingår i: Läkartidningen. - 0023-7205. ; 102:7, s. 464-466
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Tidskriftsartikel (refereegranskat)abstract
- The immediate evaluation of patients with suspected acute coronary syndrome (ACS) in the emergency department (ED) has remained almost unchanged for decades. At the same time, therapy for established ACS has undergone a remarkable and successful change towards early active intervention. Studies show that 7 out of 10 patients admitted with a suspicion of ACS do not have it, and that 2-5% of the patients with ACS are incorrectly sent home from the ED. With new diagnostic strategies, including e.g. risk prediction algorithms, new blood samples for plaque instability, special investigations like echocardiography, myocardial perfusion imaging and magnetic resonance imaging, as well as the Chest Pain Unit concept, improvements should definitely be possible. With the structured and evidence-based use of such strategies, it is our belief that more patients can be managed as outpatients, that length of stay can be shortened for those admitted, and that some patients with ACS can get an earlier adequate intervention.
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| 15. |
- Ekelund, Ulf, et al.
(författare)
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Patients with suspected acute coronary syndrome in a university hospital emergency department: an observational study.
- 2002
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Ingår i: BMC Emergency Medicine. - 1471-227X. ; 2:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Improved diagnostics in suspected acute coronary syndrome (ACS) are considered to be needed. To help clarify the current situation and the improvement potential, judged risk in the emergency department (ED) and outcome were analyzed among patients with suspected ACS at a university hospital. Methods: 157 consecutive patients with symptoms of ACS were included at the ED during 10 days. Risk of ACS was estimated in the ED for each patient based on history, physical examination and ECG by assigning them to one of four risk categories; I (obvious myocardial infarction, MI), II (strong suspicion of ACS), III (vague suspicion of ACS), and IV (no suspicion of ACS). Results: 4, 17, 29 and 50% of the patients were allocated to risk categories I-IV respectively. 74 patients (47%) were hospitalized but only 19 (26%) had ACS as the discharge diagnose. In risk categories I-IV, ACS rates were 100, 37, 12 and 0%, respectively. Of those admitted without ACS, at least 37% could probably, given perfect ED diagnostics, have been immediately discharged. 83 patients were discharged from the ED, and among them there were no hospitalizations for ACS or cardiac mortality at 6 months. Only about three patients per 24 h were considered eligible for a potential ED chest pain unit. Conclusions: Almost 75% of the patients hospitalized with suspected ACS did not have it, and some 40% of these patients could probably, given perfect immediate diagnostics, have been managed as outpatients. The potential for diagnostic improvement in the ED seems large.
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| 16. |
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| 17. |
- Holmquist, Peter, et al.
(författare)
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Early urinary changes in Tamm-Horsfall protein and epidermal growth factor in diabetic children
- 2001
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Ingår i: Pediatric Nephrology. - : Springer Science and Business Media LLC. - 1432-198X .- 0931-041X. ; 16:6, s. 488-492
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Tidskriftsartikel (refereegranskat)abstract
- Both glomerular and tubular markers have been used to follow diabetic nephropathy. However, neither albumin nor proximal tubular markers have proven useful in prepubertal diabetes. Hence we studied two markers derived from the distal tubular cells, Tamm-Horsfall protein (THP) and epidermal growth factor (EGF), The urinary excretion of THP and EGF was examined in samples obtained during the first 20 days and 1 year after diagnosis of diabetes in children aged 4-15 years. Fourteen children without and 18 with ketonuria were examined, and 17 age-matched healthy children participated as controls. The excretion rate of EGF was increased at diagnosis, while that of THP was not. After 20 days of treatment the excretion of EGF had normalized, while the excretion of THP was decreased. Similar results were obtained after 1 year. In conclusion, in spite of good metabolic control a reduced excretion of THP persisted for at least 1 year after the diagnosis of diabetes. Whether the finding of reduced excretion of THP has any biological significance awaits further study.
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| 18. |
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| 19. |
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| 20. |
- Holmquist, Peter, et al.
(författare)
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Tubular function in diabetic children assessed by Tamm-Horsfall protein and glutathione S-transferase
- 2008
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Ingår i: Pediatric Nephrology. - : Springer Science and Business Media LLC. - 1432-198X .- 0931-041X. ; 23:7, s. 1079-1083
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Tidskriftsartikel (refereegranskat)abstract
- In a previous study, we found urinary excretion of Tamm-Horsfall protein (THP) to be persistently decreased in 25% of patients during the first year after diagnosis of diabetes mellitus. We thus wanted to study another marker for distal tubular function, pi glutathione S-transferase (pi-GST) and compare this and THP with proximal tubular function evaluated with alpha-GST and alpha-1-microglobulin (HC) in patients with longer duration of diabetes. One hundred and eighty-four diabetic and 16 control children were studied with timed overnight urine collections. Median age was 14 years, and median age at diagnosis was 8 years. The urinary excretion of alpha- and pi-GST was significant lower in diabetic than control children. There were no differences in the excretion of HC and THP. Diabetic children with decreased alpha-GST had higher albumin excretion, HbA(1c) levels, and longer diabetes duration but decreased THP excretion and cystatin-C clearance compared with those with normal excretion. In contrast, a decreased pi-GST or THP excretion was not associated with such differences. Diabetic children with increased HC excretion had increased HbA(1c) levels. Diabetic children, before the stage of microalbuminuria, may have signs of both proximal and distal tubular dysfunction, which is related to diabetes duration and poor metabolic control. Alpha-GST and pi-GST seem to be more sensitive than other parameters studied.
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| 21. |
- Holmquist, Peter, et al.
(författare)
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Urinary transforming growth factor-1, collagen IV and the effect of insulin in children at diagnosis of diabetes mellitus
- 2009
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Ingår i: Scandinavian Journal of Urology and Nephrology. - : Informa UK Limited. - 0036-5599 .- 1651-2065. ; 43:2, s. 142-147
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Tidskriftsartikel (refereegranskat)abstract
- Objective. This study investigated whether metabolic derangement at diagnosis of diabetes mellitus affects the function of the basement membrane and the excretion of several components and whether insulin treatment can normalize this. It was designed to evaluate urinary excretion rates of transforming growth factor-1 (TGF-1), the carboxy-terminal domain of collagen IV (NC1) and albumin in children during the first 20 days of treatment after diagnosis of type 1 diabetes. Material and methods. Thirty-four newly diagnosed diabetic children between 4 and 16 years of age and 26 healthy children of matching age were studied with timed overnight urine collections. Urine was collected during the first 20 days of treatment. Results. Urinary excretion of albumin and TGF-1 in diabetic children were significantly increased at entry but normalized during 20 days of treatment with insulin compared with control children. In contrast, the non-significant high NC1 excretion at diagnosis did not change but became significantly increased after 20 days of insulin treatment. Overall, the kidney size was within normal limits and unaffected by treatment. The largest kidneys had less NC1 excretion (R= - 0.67, p0.05, n=13) and a lower glomerular filtration rate (R= - 0.77, p0.01, n=10) than the smallest kidneys. After 20 days of treatment TGF-1 excretion had decreased in children with kidney size 8.5 cm. Conclusion. Correction of the metabolic derangement with insulin decreased excretion of albumin and TGF-1, but had no effect on kidney size and urine NC1 excretion, presumably because the observation period was too short.
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| 22. |
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| 23. |
- Jendle, Johan, 1963-, et al.
(författare)
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Willingness to pay for health improvements associated with anti-diabetes treatments for people with type 2 diabetes
- 2010
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Ingår i: Current Medical Research and Opinion. - : Informa Healthcare. - 1473-4877 .- 0300-7995. ; 26:4, s. 917-923
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: This study aimed to investigate the most important consequences of diabetes medication, as measured by the patients' willingness to pay (WTP). Research design and methods: People in Sweden were recruited using existing nationwide e-mail panels if they were adults (>= 18 years) with type 2 diabetes and were receiving pharmacological anti-diabetes treatment(s). Data were collected electronically and results were analysed using a standard statistical model designed for choice games (conditional logit). Six characteristics relating to treatment of diabetes were examined: weight (gain or loss), mean glycated haemoglobin level (HbA(1c)), hypoglycaemic events, nausea, need for injections (with or independently of meals), and blood glucose testing. Results: A total of 461 people with type 2 diabetes (291 males; 170 females) completed an internet questionnaire and were eligible for inclusion. Participants placed high value on weight loss and nausea avoidance; they would pay 176 Swedish Krona (SEK)/(sic)15.61 per month to lose 1 kg, and would pay SEK 560 ((sic)49.67) per month to avoid nausea completely. Patients wanting to reduce the number of hypoglycaemic events from three per month to none were willing to pay SEK 419 ((sic)37.17) per month. Patients valued a 1 percentage point reduction in HbA(1c) at SEK 414 ((sic)36.72) per month. Participants preferred taking tablets to injections and required a compensation of SEK 376 ((sic)33.35) to accept one injection/day. Injections independent of meals were preferred to injections with meals (WTP: SEK 140/(sic)12.42 per month). Potential limitations of this study are that the preferences expressed may not match preferences in real-life situations, and bias through the use of electronic questionnaire, which restricted participation to those with access to, and experience with, the internet. Conclusion: People with type 2 diabetes were willing to pay a considerable amount of money each month to lose weight, reduce or avoid hypoglycaemic events and reduce HbA(1C).
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| 24. |
- Kalani, Majid, et al.
(författare)
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Beneficial effects of dalteparin on haemostatic function and local tissue oxygenation in patients with diabetes, severe vascular disease and foot ulcers.
- 2007
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Ingår i: Thrombosis research. - : Elsevier BV. - 0049-3848 .- 1879-2472. ; 120:5, s. 653-61
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: A state of hypercoagulation and fibrinolytic dysfunction is present in individuals with diabetes, which may contribute to disturbed skin microcirculation and impaired ulcer healing. We have previously reported an improved outcome of chronic diabetic foot ulcers during treatment with dalteparin. In the present study we investigated the effects of dalteparin on skin microcirculation and haemostatic function. MATERIALS AND METHODS: 87 patients with diabetes, peripheral arterial obliterative disease and chronic foot ulcers were investigated in a prospective, randomised, double-blind and placebo-controlled study. They were randomised to treatment with subcutaneous injections of 5000 U dalteparin (n=44) or placebo (n=43), once daily until ulcer healing or for a maximum of six months. Plasma fibrinogen, fibrin gel structure [permeability coefficient (Ks) and fiber mass/length ratio (mu)], prothrombin fragment 1+2 (F1+2) antigen, plasminogen activator inhibitor-1 (PAI-1) activity and tissue plasminogen activator (tPA) antigen were analysed before randomization (baseline value), and at the end of the treatment period. The skin microcirculation of the foot was investigated by transcutaneous oxygen tension (TcPO(2)) and laser Doppler fluxmetry (LDF). RESULTS: The changes (Delta-values) of Ks, mu, tPA and TcPO(2) were higher (p<0.05) during treatment with dalteparin, as compared to the changes during treatment with placebo. At baseline, plasma fibrinogen and Ks were significantly correlated to TcPO(2). CONCLUSIONS: Local skin oxygenation improved and a less thrombogenic fibrin gel structure was formed in patients treated with dalteparin. Beneficial effects on haemostatic function are likely to contribute to the improved skin oxygenation observed during treatment with dalteparin.
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| 25. |
- Kalani, Majid, et al.
(författare)
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Effect of dalteparin on healing of chronic foot ulcers in diabetic patients with peripheral arterial occlusive disease: a prospective, randomized, double-blind, placebo-controlled study.
- 2003
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Ingår i: Diabetes care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 26:9, s. 2575-80
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Chronic foot ulcers are a common, severe, and expensive complication threatening life and limb in patients with diabetes. The aim of the present study was to investigate the effect of dalteparin on ulcer outcome in patients with diabetes, peripheral arterial occlusive disease, and chronic foot ulcers. RESEARCH DESIGN AND METHODS: A total of 87 patients were investigated in a prospective, randomized, double-blind, placebo-controlled trial. Participants were randomized to treatment with subcutaneous injection of 5000 units dalteparin (Fragmin, Pharmacia Corporation; n = 44) or an equivalent volume of physiological saline (n = 43) once daily until ulcer healing or for a maximum of 6 months. Ulcer outcome was investigated by evaluating the number of patients 1). who healed with intact skin; 2). in whom the study ulcer was improved, unchanged, or impaired; or 3). who were amputated above or below the ankle level, as compared with control subjects. RESULTS: Two patients, one on dalteparin and one on placebo, dropped out of the study. Ulcer outcome was significantly better (P = 0.042, two-sided chi(2) test for trend) in the dalteparin group (n = 43) compared with the placebo group (n = 42). A total of 29 patients healed with intact skin (n = 14) or decreased the ulcer area >or=50% (n = 15) in the dalteparin group compared with 20 (n = 9 and 11, respectively) in the placebo group. Five patients in each group showed impaired ulcer healing, i.e., the ulcer area increased >or=50%. Two patients in the dalteparin group were amputated compared with eight in the placebo group. Time to healing with intact skin was 17 +/- 8 weeks in the dalteparin group compared with 16 +/- 7 weeks in placebo group (NS). CONCLUSIONS: The results of the present study indicate that dalteparin improves the outcome of chronic foot ulcers in diabetic patients with peripheral arterial occlusive disease.
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| 26. |
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| 27. |
- Lind, Marcus, 1976, et al.
(författare)
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Design and methods of a randomised double-blind trial of adding liraglutide to control HbA1c in patients with type 2 diabetes with impaired glycaemic control treated with multiple daily insulin injections (MDI-Liraglutide trial)
- 2015
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Ingår i: PRIMARY CARE DIABETES. - : Elsevier BV. - 1751-9918 .- 1878-0210. ; 9:1, s. 15-22
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: Patients with type 2 diabetes are generally treated in primary care setting and as a final treatment step to obtain good glycaemic control, multiple daily insulin injections (MDI) are generally used. The aim of this study is to evaluate the effect of GLP-1 analogue liraglutide on glycaemic control in patients with type 2 diabetes treated with MDI with inadequate glycaemic control. METHODS: Overweight and obese patients with type 2 diabetes and impaired glycaemic control treated with MDI were randomised to liraglutide or placebo over 24 weeks. Masked continuous glucose monitoring was performed at baseline and during the trial. The primary endpoint was the change in haemoglobin A1c from baseline to week 24. Additional endpoints include changes in weight, fasting glucose, glycaemic variability, treatment satisfaction, insulin dose, hypoglycaemias, blood pressure and blood lipid levels. RESULTS: Recruitment occurred between February 2013 and February 2014. A total of 124 patients were randomised. Study completion is anticipated in August 2014. CONCLUSIONS: It is expected that the results of this study will establish whether adding liraglutide to patients with type 2 diabetes treated with MDI will improve glycaemic control, lower body weight, and influence glycaemic variability.
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| 28. |
- Lind, Marcus, 1976, et al.
(författare)
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Glucagon-like peptide 1 (GLP-1) analogue combined with insulin reduces HbA1c and weight with low risk of hypoglycemia and high treatment satisfaction
- 2012
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Ingår i: Primary Care Diabetes. - Oxon, United Kingdom : Elsevier BV. - 1751-9918 .- 1878-0210. ; 6:1, s. 41-46
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Tidskriftsartikel (refereegranskat)abstract
- Aims: To evaluate the effects of adding glucagon-like peptide-1 (GLP-1) analogue therapy to insulin on glycated hemoglobin (HbA1c), weight, insulin dosage, treatment satisfaction, and risk of hypoglycaemia. Methods: Type 2 diabetes patients with insulin therapy receiving a GLP-1 analogue at 4 Swedish centers were studied. Hypoglycemia was evaluated using glucometers and patient self-report. The Diabetes Treatment Satisfaction Questionnaire (DTSQ) was used to evaluate treatment satisfaction. Results: Among 65 patients studied, 4 discontinued therapy, none due to hypoglycemia, and there were no suspected severe adverse events. Among 61 patients who remained on therapy over a mean of 7.0 months, 40 were treated with liraglutide and 21 with exenatide. HbA1c decreased from a mean of 8.9% (82.4 mmol/mol) to 7.9% (71.9 mmol/mol) (p < 0.001), weight decreased from 111.1 kg to 104.0 kg (p<0.001) and insulin doses were reduced from 91.1U to 52.2 U (p < 0.001). There was one patient with severe hypoglycemia. The mean number of asymptomatic hypoglycemia per patient and month, reported for the last month (0.085 below 4.0 mmol/l and 0 below 3.0 mmol/l) and documented symptomatic hypoglycemia (0.24 below 4.0 mmol/l and 0.068 below 3.0 mmol/l) was low. The DTSQc showed higher treatment satisfaction than with the previous regimen of 11.9 (scale -18 to +18 points, p<0.001). Conclusions: The addition of GLP-1 analogues to insulin in patients with type 2 diabetes is associated with reductions in HbA1c, weight, and insulin dose, along with a low risk of hypoglycemia and high treatment satisfaction.
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| 29. |
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| 30. |
- Lindqvist, A, et al.
(författare)
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Artery blood pressure oscillation after active standing up: an indicator of sympathetic function in diabetic patients
- 1997
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Ingår i: Clinical Physiology. - : Wiley. - 1365-2281 .- 0144-5979. ; 17:2, s. 159-169
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 31. |
- Lövestam Adrian, Monica, et al.
(författare)
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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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Ingår i: Journal of Diabetes and its Complications. - 1873-460X. ; 15:6, s. 287-294
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Tidskriftsartikel (refereegranskat)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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| 32. |
- Lövestam Adrian, Monica, et al.
(författare)
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Sight-threatening retinopathy is associated with lower mortality in type 2 diabetic subjects: A 10-year observation study.
- 2007
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Ingår i: Diabetes Research and Clinical Practice. - : Elsevier BV. - 1872-8227 .- 0168-8227. ; 77:1, s. 141-147
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Tidskriftsartikel (refereegranskat)abstract
- Aims: To study associations between diabetic retinopathy and development of stroke, myocardial infarction and death in type 2 diabetic patients. Methods: During a 10-year observation period, 363 type 2 diabetic patients (diagnosis >= 30 years of age) attending an outpatient clinic were studied regarding the prevalence and incidence of retinopathy and associated risk factors, i.e., (HbA(1c), blood pressure, albuminuria, plasma creatinine, age, sex and diabetes duration) in relation to the development of myocardial infarction, stroke and death. The degree of retinopathy was classified as no retinopathy, background or sight-threatening retinopathy, i.e., clinically significant macular edema, severe non-proliferative or proliferative retinopathy. Results: During the study period, 62 patients had had myocardial infarction, 54 stroke and 99 patients died. Patients with sight-threatening retinopathy at baseline (n = 41) had a 2.2-fold increased (p < 0.01) risk for death compared to patients with no or background retinopathy, even when controlled for medical risk factors. When adjusted for medical risk factors, patients with no retinopathy at baseline (n = 226) who remained without retinopathy or developed background retinopathy (n = 187) during the study period, had a 3.6-fold increased risk for death (95% CI, 1.1, 11.8), (p = 0.03), compared to patients who developed sight-threatening retinopathy (n = 39), while the incidence of myocardial infarction did not differ. More patients who developed sight-threatening retinopathy were treated with ACE inhibitors than patients who did not (41% versus 24%; p = 0.03). Conclusion: Despite more medical risk factors, patients who developed sight-threatening retinopathy had lower mortality compared to patients with no or background retinopathy at follow-up. More patients who developed sight-threatening retinopathy were treated with ACE inhibitors but this seemed not to have influenced the lower mortality rate in this group, whereas the use of ACE inhibitors in patients who did not develop sight-threatening retinopathy was connected with lower mortality rate.
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| 33. |
- Lövestam-Adrian, Monica, et al.
(författare)
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Type 1 diabetes patients with severe non-proliferative retinopathy may benefit from panretinal photocoagulation.
- 2003
-
Ingår i: Acta Ophthalmologica Scandinavica. - : Wiley. - 1395-3907. ; 81:3, s. 221-225
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Tidskriftsartikel (refereegranskat)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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| 34. |
- Mistry, Hiten D., et al.
(författare)
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Evidence of Augmented Intrarenal Angiotensinogen Associated With Glomerular Swelling in Gestational Hypertension and Preeclampsia : Clinical Implications
- 2019
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Ingår i: Journal of the American Heart Association. - 2047-9980. ; 8:13
-
Tidskriftsartikel (refereegranskat)abstract
- Background AGT (angiotensinogen) synthesis occurs in renal proximal tubular epithelial cells, independent from systemic AGT , as a component of the intrarenal renin-angiotensin system. We investigated urinary AGT , as a biomarker for renin-angiotensin system activation, and electrolyte concentrations, in relation to glomerular volume, as a proxy for glomerular endotheliosis in renal biopsy tissue from pregnant normotensive control and hypertensive women. Methods and Results Urine samples were collected from normotensive control (n=10), gestational hypertensive (n=6), and pre-eclamptic (n=16) women at the time a renal biopsy was obtained. Samples were collected from Lund University Hospital between November 1999 and June 2001. Urinary AGT , potassium, and sodium were measured, normalized to urinary creatinine. Mean glomerular volume was estimated from biopsy sections. AGT protein expression and localization were assessed in renal biopsies by immunohistochemistry. Urinary AGT concentrations were higher in hypertensive pregnancies (median, gestational hypertension: 11.3 ng/mmol [interquartile range: 2.8-13.6]; preeclampsia: 8.4 ng/mmol [interquartile range: 4.2-29.1]; normotensive control: 0.6 ng/mmol [interquartile range: 0.4-0.8]; P<0.0001) and showed a positive relationship with estimated mean glomerular volume. Urinary potassium strongly correlated with urinary AGT ( P<0.0001). Although numbers were small, AGT protein was found in both glomeruli and proximal tubules in normotensive control but was present only in proximal tubules in women with hypertensive pregnancy. Conclusions This study shows that pregnant women with gestational hypertension or preeclampsia have increased urinary AGT and potassium excretion associated with signs of glomerular swelling. Our data suggest that the kidneys of women with hypertensive pregnancies and endotheliosis have inappropriate intrarenal renin-angiotensin system activation, which may contribute toward the pathogenesis of hypertension and renal injury.
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| 35. |
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| 36. |
- Ohlsson, Sophie, et al.
(författare)
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Monocyte chemoattractant protein 1 is a prognostic marker in ANCA-associated small vessel vasculitis.
- 2009
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Ingår i: Mediators of Inflammation. - New York, NY, USA : Hindawi Limited. - 0962-9351 .- 1466-1861. ; 2009:Jul 5
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The (anti neutrophil cytoplasmatic autoantibody ANCA), associated small vessel vasculitides (ASVV) are relapsing-remitting inflammatory disorders, involving various organs, such as the kidneys. (Monocyte chemoattractant protein 1 MCP-1) has been shown to be locally up regulated in glomerulonephritis and recent studies have pointed out MCP-1 as a promising marker of renal inflammation. Here we measure urinary cytokine levels in different phases of disease, exploring the possible prognostic value of MCP-1, together with (interleukin 6 IL-6), (interleukin 8 IL-8) and (immunoglobulin M IgM). METHODS: MCP-1, IL-6 and IL-8 were measured using commercially available ELISA kits, whereas IgM in the urine was measured by an in-house ELISA. RESULTS: The MCP-1 levels in urine were significantly higher in patients in stable phase of the disease, compared with healthy controls. Patients in stable phase, with subsequent adverse events; had significantly higher MCP-1 values than patients who did not. MCP-1 and IgM both tended to be higher in patients relapsing within three months, an observation, however, not reaching statistical significance. Urinary levels of IL-6 correlated with relapse tendency, and IL-8 was associated with disease outcome. CONCLUSIONS: Patients with ASVV have raised cytokine levels in the urine compared to healthy controls, even during remission. Raised MCP-1 levels are associated with poor prognosis and possibly also with relapse tendency. The association with poor prognosis was stronger for U-MCP-1 than for conventional markers of disease like CRP, BVAS, and ANCA, as well as compared to candidate markers like U-IgM and U-IL-8. We thus consider U-MCP-1 to have promising potential as a prognostic marker in ASVV.
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| 37. |
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| 38. |
- Padmanabhan, Sandosh, et al.
(författare)
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Genome-Wide Association Study of Blood Pressure Extremes Identifies Variant near UMOD Associated with Hypertension
- 2010
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Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 6:10
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Tidskriftsartikel (refereegranskat)abstract
- Hypertension is a heritable and major contributor to the global burden of disease. The sum of rare and common genetic variants robustly identified so far explain only 1%-2% of the population variation in BP and hypertension. This suggests the existence of more undiscovered common variants. We conducted a genome-wide association study in 1,621 hypertensive cases and 1,699 controls and follow-up validation analyses in 19,845 cases and 16,541 controls using an extreme case-control design. We identified a locus on chromosome 16 in the 59 region of Uromodulin (UMOD; rs13333226, combined P value of 3.6x10(-11)). The minor G allele is associated with a lower risk of hypertension (OR [95% CI]: 0.87 [0.84-0.91]), reduced urinary uromodulin excretion, better renal function; and each copy of the G allele is associated with a 7.7% reduction in risk of CVD events after adjusting for age, sex, BMI, and smoking status (H.R. = 0.923, 95% CI 0.860-0.991; p = 0.027). In a subset of 13,446 individuals with estimated glomerular filtration rate (eGFR) measurements, we show that rs13333226 is independently associated with hypertension (unadjusted for eGFR: 0.89 [0.83-0.96], p = 0.004; after eGFR adjustment: 0.89 [0.83-0.96], p = 0.003). In clinical functional studies, we also consistently show the minor G allele is associated with lower urinary uromodulin excretion. The exclusive expression of uromodulin in the thick portion of the ascending limb of Henle suggests a putative role of this variant in hypertension through an effect on sodium homeostasis. The newly discovered UMOD locus for hypertension has the potential to give new insights into the role of uromodulin in BP regulation and to identify novel drugable targets for reducing cardiovascular risk.
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| 39. |
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| 40. |
- Rippe, Catarina, et al.
(författare)
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Size and charge selectivity of the glomerular filter in early experimental diabetes in rats
- 2007
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Ingår i: American Journal of Physiology: Renal, Fluid and Electrolyte Physiology. - : American Physiological Society. - 0363-6127. ; 293:5, s. 1533-1538
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Tidskriftsartikel (refereegranskat)abstract
- Microalbuminuria is an early sign of diabetic nephropathy. The aim of the present study was to investigate whether the changes of the glomerular filtration barrier in early experimental diabetes are due to size- or charge-selective alterations. Wistar rats, made diabetic by streptozotocin (STZ) and having their blood glucose maintained at similar to 20 mM for 3 or 9 wk, were compared with age-matched controls. Glomerular clearances of native albumin (C1-HSA) and neutralized albumin (C1-nHSA) were assessed using a renal uptake technique. Glomerular filtration rate and renal plasma flow were assessed using Cr-51-EDTA and [ I-125]iodohippurate, respectively. In a separate set of animals, diabetic for 9 wk, and in controls, glomerular sieving coefficients (theta) for neutral FITC-Ficoll (molecular radius: 15-90 angstrom) were assessed using size exclusion chromatography. At 3 wk of diabetes, C1-HSA and C1-nHSA remained unchanged, indicating no alteration in either size or charge selectivity. By contrast, at 9 wk of diabetes, there was a twofold increase of C1-HSA, whereas C1-nHSA remained largely unchanged, at first suggesting a glomerular charge defect. However, according to a two-pore model, the number of large pores, assessed from both Ficoll and C1-HSA, increased twofold. In addition, a small reduction in proximal tubular reabsorption was observed at 3 wk, which was further reduced at 9 wk. In conclusion, no functional changes were observed in the glomerular filtration barrier at 3 wk of STZ-induced diabetes, whereas at 9 wk there was a decrease in size selectivity due to an increased number of large glomerular pores.
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| 41. |
- Sejdiu, Ilir, et al.
(författare)
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Decreased urinary concentration of Tamm-Horsfall protein is associated with development of renal failure and cardiovascular death within 20 years in type 1 but not in type 2 diabetic patients.
- 2008
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Ingår i: Scandinavian Journal of Urology and Nephrology. - : Informa UK Limited. - 0036-5599 .- 1651-2065. ; 2:4, s. 168-174
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Tidskriftsartikel (refereegranskat)abstract
- Objective. The first changes in the diabetic kidney are glycogen deposits in the epithelial cells of the thick ascending limb of Henle. These cells produce Tamm-Horsfall protein (THP). Is low excretion of THP associated with the development of renal insufficiency or cardiovascular disease? Material and methods. Urine samples were collected at baseline in patients with type 1 (n=131) and type 2 (n=108) diabetes who were followed for a mean of 14 years (range 1-20 years) and 4.5 years (range 1-15 years), respectively. Results. Twenty percent of type 1 and 54% of type 2 diabetic patients died and 24% and 29%, respectively developed uraemia. A decreased urinary concentration of THP (u-THP) was associated with an eight-fold increased risk of renal failure and cardiovascular death in type 1 but not in type 2 diabetic patients, irrespective of the degree of albuminuria and glycosylated haemoglobin and blood pressure levels. There were no differences in the degrees of albuminuria, serum creatinine or u-THP between the two types of diabetic patients at baseline. Low u-THP occurred in 8% and 9% of normoalbuminuric type 1 and type 2 diabetic patients, respectively. Conclusion. A decreased u-THP was associated with an eight-fold increased risk of cardiovascular death and uraemia in type 1 but not in type 2 diabetic patients.
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| 42. |
- Strevens, Helena, et al.
(författare)
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Serum cystatin C for assessment of glomerular filtration rate in pregnant and non-pregnant women. Indications of altered filtration process in pregnancy.
- 2002
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Ingår i: Scandinavian Journal of Clinical & Laboratory Investigation. - : Informa UK Limited. - 1502-7686 .- 0036-5513. ; 62:2, s. 141-147
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Tidskriftsartikel (refereegranskat)abstract
- Serum cystatin C is believed to reflect the glomerular filtration rate (GFR) more closely than serum creatinine in many contexts and a reference interval for serum cystatin C in term pregnancy has been defined to enable its use also in pregnant women. However, serum cystatin C levels were not found to be decreased in term pregnancy, though GFR of low molecular mass substances is known to increase by at least 40% by the third trimester. The aim of this study was therefore to determine whether serum cystatin C is a reliable GFR marker also in pregnant women. GFR was determined by measurement of plasma clearance of iohexol in 48 previously healthy women in their third trimester and in 12 healthy nonpregnant women, and was compared with their serum levels of cystatin C and creatinine. Both serum cystatin C and creatinine levels were significantly related to GFR for both pregnant and non-pregnant women. However, the correlation between cystatin C and GFR was set at different levels for pregnant and nonpregnant women. Our results indicate a physiological difference between the filtration processes in kidneys of pregnant and non-pregnant women, whether it is size-dependent, configuration-dependent or charge-dependent. Nevertheless, serum cystatin C seems to reflect GFR reliably in both non-pregnant and pregnant, healthy and hypertensive women.
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| 43. |
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| 44. |
- Svensson, Maria, et al.
(författare)
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Signs of nephropathy may occur early in young adults with diabetes despite modern diabetes management : Results from the nationwide population-based Diabetes Incidence Study in Sweden (DISS)
- 2003
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Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 26:10, s. 2903-2909
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE - To estimate the occurrence of early-onset renal involvement in a nationwide population-based cohort of young adults with diabetes in Sweden and relate the findings to glycemic control, type of diabetes, sex, smoking, and blood pressure. RESEARCH DESIGN AND METHODS - The Diabetes Incidence Study in Sweden aims to register all incident cases of diabetes in the age-group 15-34 years. In 1987-1988, 806 patients were reported and invited to participate in a follow-up study focusing on microvascular complications. Of them, 469 subjects participated. The assessment was based on questionnaires (n = 469), blood samples (n = 424), urine samples (n = 251) and, when appropriate, medical records (n = 186). RESULTS - During the follow-up time, median 9 years (range 6-12), 31 of 469 patients (6.6%) with incipient or overt diabetic nephropathy (i.e., micro- or macroalbuminuria) were found, 24 of 426 (5.6%) in type 1 and 7 of 43 (16%) in type 2 diabetic subjects (P = 0.016). Additionally, 24 of 31 patients (77%) had microalbuminuria and 7 (23%) had macroalbuminuria, which mainly occurred in patients with type 2 diabetes. In a Cox regression analysis, high mean HbA1c during the follow-up period and high blood pressure at follow-up increased the risk of developing signs of nephropathy (P = 0.020 and P = 0.003, respectively). Compared with patients with type 1 diabetes, those with type 2 diabetes tended to have an increased risk of renal involvement (P = 0.054) when adjusting for sex, tobacco use, glycemic control, and blood pressure. CONCLUSIONS - Despite modern treatment and self-monitoring of blood glucose, young adult patients with diabetes may still develop renal involvement during the first 10 years of diabetes duration. Inadequate HbA 1c high blood pressure, and type 2 diabetes appear to be risk markers for early occurrence of diabetic nephropathy.
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| 45. |
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| 46. |
- Swärd, Per, et al.
(författare)
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Patterns of urinary albumin and IgM associate with markers of vascular ageing in young to middle-aged individuals in the Malmö offspring study
- 2020
-
Ingår i: BMC Cardiovascular Disorders. - : Springer Science and Business Media LLC. - 1471-2261. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Increased urinary excretion of IgM and low-grade albuminuria are associated with increased risk of cardiovascular morbidity and mortality. The objective of this study was to investigate the association between urinary IgM, albuminuria, and vascular parameters reflecting arterial structure and function. METHODS: Subjects of the present study were from the Malmö Offspring study (MOS) cohort, and included 1531 offspring (children and grand-children) to first-generation subjects that participated in the Malmö Diet Cancer-Cardiovascular Arm study cohort. At baseline, technical measurements of arterial stiffness (carotid-femoral pulse wave velocity; c-f PWV), carotid arterial morphology, 24-h ambulatory blood pressure recordings, ankle-brachial-index (ABI), and evaluation of endothelial function (reactive hyperemia index, RHI) were performed. Urinary (U) IgM, U-albumin, and U-creatinine were measured. Multivariate adjusted logistic regression was used to test whether U-IgM excretion and increasing urinary albumin excretion were related to vascular parameters. RESULTS: Detectable U-IgM was independently associated with higher systolic blood pressure, odds ratio (OR) 1.021, 95% confidence interval (CI, 1.003-1.039), p = 0.025 and lower ABI; ABI dx: OR 0.026, 95% CI (0.002-0.381), p = 0.008, ABI sin: OR 0.040, 95% CI (0.003-0.496), p = 0.012. Low-grade albuminuria was independently associated with systolic and diastolic blood pressure, aortic blood pressure, the c-f PWV and the number of carotid intima plaques (p < 0.05). CONCLUSIONS: In young to middle-aged, mostly healthy individuals, increased U-IgM excretion and low-grade albuminuria are associated with adverse vascular parameters. Increased U-IgM excretion may reflect subclinical peripheral atherosclerosis, whereas increased U-albumin excretion is associated with a wide range of cardiovascular abnormalities. This may reflect different pathophysiological mechanisms.
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| 47. |
- Tencer, Jan, et al.
(författare)
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Diagnostic and prognostic significance of proteinuria selectivity index in glomerular diseases
- 2000
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Ingår i: Clinica Chimica Acta. - 0009-8981. ; 297:1-2, s. 73-83
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Tidskriftsartikel (refereegranskat)abstract
- The proteinuria selectivity index (SI) describes changes of the glomerular permeability for macromolecules. In the present study, we examine the implications of SI as a diagnostic (199 patients) and a prognostic (49 patients) marker in glomerular diseases. Using SI based on alpha(2)-macroglobulin (alpha(2)-M-SI) or on IgM (IgM-SI) we found that minimal change nephropathy could be discriminated by low SI values and crescentic necrotizing glomerulonephritis by high SI values compared to other diseases. SI based on IgG (IgG-SI) was less useful in determining specific diagnoses. During a follow-up of 46 months creatinine clearance (Cr cl) decreased 36% in a group of patients with high IgG-SI (>0.2) and 38% in a group of patients with high IgM-SI (>1.5(-3)) compared to only 8% in patients with low IgG-SI (
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- Tofik, Rafid, et al.
(författare)
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Increased urinary IgM excretion in patients with chest pain due to coronary artery disease
- 2013
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Ingår i: BMC Cardiovascular Disorders. - : Springer Science and Business Media LLC. - 1471-2261. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Background: Micro-albuminuria is a recognized predictor of cardiovascular morbidity and mortality in patients with coronary artery disease. We have previously reported, in diabetic and non-diabetic patients, that an increased urinary excretion of IgM is associated with higher cardiovascular mortality. The purpose of this study was to investigate the pattern of urinary IgM excretion in patients with acute coronary syndrome (ACS) and its correlation to cardiovascular outcome. Methods: Urine albumin, and IgM to creatinine concentration ratios were determined in 178 consecutive patients presenting with chest pain to the Department of Emergency Medicine (ED) at the University Hospital of Lund. Fifty eight (23 female) patients had ACS, 55 (19 female) patients had stable angina (SA), and 65 (35 female) patients were diagnosed as non-specific chest pain (NS). Results: Urine albumin and IgM excretions were significantly higher in patients with ACS (p = 0.001, and p = 0.029, respectively) compared to patients with NS-chest pain. During the 2 years follow-up time, 40 (19 female) patients suffered a new major cardiovascular event (ACS, acute heart failure, stroke) and 5 (4 male/1 female) patients died of cardiovascular cause. A high degree of albuminuria and IgM-uria significantly predicted cardiovascular mortality and morbidity (HR = 2.89, 95% CI: 1.48 - 5.66, p = 0.002). Microalbuminuric patients (>= 3 mg/mmol) with high IgM-uria (>= 0.005 mg/mmol) had a 3-fold higher risk for cardiovascular new events compared to patients with low IgM-uria (RR = 3.3, 95% CI: 1.1 - 9.9, p = 0.001). Conclusion: In patients with chest pain, an increased urine IgM excretion, is associated with coronary artery disease and long-term cardiovascular complications. Measuring urine IgM concentration could have a clinical value in risk stratification of patients with ACS.
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- Tofik, Rafid, et al.
(författare)
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Increased urine IgM excretion predicts cardiovascular events in patients with type 1 diabetes nephropathy.
- 2009
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Ingår i: BMC Medicine. - : Springer Science and Business Media LLC. - 1741-7015. ; 7:Aug 4
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Diabetic nephropathy, a major complication of diabetes, is characterized by progressive renal injury and increased cardiovascular mortality. An increased urinary albumin excretion due dysfunction of the glomerular barrier is an early sign of diabetic nephropathy. An increased urinary excretion of higher molecular weight proteins such as IgM appears with progression of glomerular injury. We aim here to study the prognostic significance of urine IgM excretion in patients with type 1 diabetes mellitus (type 1 diabetic nephropathy). METHODS: This is an observational study of 139 patients with type 1 diabetes mellitus (79 males and 60 females) under routine care at the diabetic outpatient clinic at the Lund University Hospital. The median follow-up time was 18 years (1 to 22) years. Urine albumin and urine IgM concentration were measured at time of recruitment. RESULTS: Overall 32 (14 male and 18 female) patients died in a cardiovascular event and 20 (11 male and 9 female) patients reached end-stage renal disease. Univariate analysis indicated that patient survival and renal survival were inversely associated with urine albumin excretion (RR = 2.9 and 5.8, respectively) and urine IgM excretion (RR = 4.6 and 5.7, respectively). Stratified analysis demonstrated that in patients with different degrees of albuminuria, the cardiovascular mortality rate and the incidence of end-stage renal disease was approximately three times higher in patients with increased urine IgM excretion. CONCLUSION: An increase in urinary IgM excretion in patients with type 1 diabetes is associated with an increased risk for cardiovascular mortality and renal failure, regardless of the degree of albuminuria.
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