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| 2. |
- Afghahi, Henri, 1966, et al.
(författare)
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Ongoing treatment with renin-angiotensin-aldosterone-blocking agents does not predict normoalbuminuric renal impairment in a general type 2 diabetes population.
- 2013
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Ingår i: Journal of diabetes and its complications. - : Elsevier BV. - 1873-460X .- 1056-8727. ; 27:3, s. 229-34
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Tidskriftsartikel (refereegranskat)abstract
- AIM: To examine the prevalence and the clinical characteristics associated with normoalbuminuric renal impairment (RI) in a general type 2 diabetes (T2D) population. METHODS: We included 94 446 patients with T2D (56% men, age 68.3±11.6years, BMI 29.6±5.3kg/m(2), diabetes duration 8.5±7.1years; means±SD) with renal function (serum creatinine) reported to the Swedish National Diabetes Register (NDR) in 2009. RI was defined as estimated glomerular filtration (eGFR)<60ml/min/1.73m(2) and albuminuria as a urinary albumin excretion rate (AER)>20μg/min. We linked the NDR to the Swedish Prescribed Drug Register, and the Swedish Cause of Death and the Hospital Discharge Register to evaluate ongoing medication and clinical outcomes. RESULTS: 17% of the patients had RI, and 62% of these patients were normoalbuminuric. This group of patients had better metabolic control, lower BMI, lower systolic blood pressure and were more often women, non-smokers and more seldom had a history of cardiovascular disease as compared with patients with albuminuric RI. 28% of the patients with normoalbuminuric RI had no ongoing treatment with any RAAS-blocking agent. Retinopathy was most common in patients with RI and albuminuria (31%). CONCLUSIONS: The majority of patients with type 2 diabetes and RI were normoalbuminuric despite the fact that 25% of these patients had no ongoing treatment with RAAS-blocking agents. Thus, RI in many patients with type 2 diabetes is likely to be caused by other factors than diabetic microvascular disease and ongoing RAAS-blockade.
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| 3. |
- Agardh, Carl-David, et al.
(författare)
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Altered endothelial/pericyte ratio in Goto-Kakizaki rat retina
- 1997
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Ingår i: Journal of Diabetes and its Complications. - 1873-460X .- 1056-8727. ; 11:3, s. 158-162
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Tidskriftsartikel (refereegranskat)abstract
- The Goto-Kakizaki (GK) rat represents a model of hereditary non-insulin-dependent diabetes mellitus (NIDDM), characterized by nonobesity, mild hyperglycemia from early life, impaired glucose tolerance test results, and a markedly defective insulin response to glucose. The rats develop signs of both nephropathy and neuropathy, but, to our knowledge, retinal changes have not been reported so far in this model of NIDDM. Hence, the aim of the present study was to assess whether morphological vascular changes could be demonstrated in retinal vessel preparations of GK rats. The endothelial/pericyte ratio was found to be higher in GK rats aged 8 months as well as after 24-30 months compared to their matched controls (2.3 +/- 0.2 versus 2.0 +/- 0.1; p < 0.01, and 2.6 +/- 0.2 versus 1.9 +/- 0.1; p < 0.001, respectively). Furthermore, in 24 to 30-months-old GK rats, the endothelial/pericyte ratio was higher than in 8 month old GK rats (p < 0.05). Thus, the GK rat appears to be a suitable model for experimental studies of chronic complications, including diabetic retinopathy, in NIDDM.
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- Agardh, Carl-David, et al.
(författare)
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Clinical evidence for the safety of GAD65 immunomodulation in adult-onset autoimmune diabetes.
- 2005
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Ingår i: Journal of Diabetes and its Complications. - : Elsevier BV. - 1873-460X .- 1056-8727. ; 19:4, s. 238-246
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this Phase II study was to evaluate if alum-formulated human recombinant GAD65 is safe and does not compromise beta cell function. The study was conducted as a randomized, double blind, placebo-controlled, dose-escalation clinical trial in a total of 47 Latent Autoimmune Diabetes in Adults (LADA) patients who received either placebo or 4, 20, 100, or 500 μg Diamyd subcutaneously at Weeks 1 and 4. Safety evaluations, including neurology, beta cell function tests, diabetes status assessment, hematology, biochemistry, and cellular and humoral immunological markers, were repeatedly assessed over 24 weeks. None of the patients had significant study-related adverse events (AE). Fasting c-peptide levels at 24 weeks were increased compared with placebo (P=.0015) in the 20 μg but not in the other dose groups. In addition, both fasting (P=.0081) and stimulated (P=.0236) c-peptide levels increased from baseline to 24 weeks in the 20 μg dose group. GADA log levels clearly increased (P=.0002) in response to 500 μg Diamyd. The CD4+CD25+/CD4+CD25− cell ratio increased (P=.0128) at 24 weeks in the 20 μg group. No sudden increase in HbA1c or plasma glucose or decrease in beta cell function was observed in any of the dose groups. These positive findings for clinical safety further support the clinical development of Diamyd as a therapeutic to prevent autoimmune diabetes.
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| 5. |
- 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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| 6. |
- Agardh, Carl-David, et al.
(författare)
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Irreversible progression of severe retinopathy in young type I insulin-dependent diabetes mellitus patients after improved metabolic control
- 1992
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Ingår i: Journal of Diabetes and its Complications. - 1873-460X. ; 6:2, s. 96-100
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Tidskriftsartikel (refereegranskat)abstract
- The impact of metabolic control on the development of rapidly progressive severe retinopathy was studied in 14 young type I insulin-dependent diabetes mellitus (IDDM) patients. Glycosylated hemoglobin (HbAlc) levels 45 months prior to and 12 months after the diagnosis of retinopathy were compared with HbAlc levels in 17 type I IDDM patients with no or minimal background retinopathy, matched for age and duration of diabetes. HbAlc levels were generally higher in patients with severe retinopathy (p less than 0.05) from 39 months until 6 months before the diagnosis of retinopathy. Thereafter, there was a gradual decrease in HbAlc levels reaching the same level as in control patients 6 months after diagnosis of retinopathy. Patients with severe retinopathy required higher doses of insulin prior to the diagnosis of retinopathy (p less than 0.05), but the insulin requirement decreased, and 12 months afterward, the insulin dosage was similar to patients with background retinopathy. Systolic blood pressure levels were slightly increased and higher in patients with severe retinopathy compared with control patients from 18 months before to diagnosis of retinopathy (p less than 0.05). Diastolic blood pressure levels likewise differed at 18 and 12 months before and at the time of diagnosis of retinopathy as well as 12 months afterward (p less than 0.05); however, no differences were seen in urinary albumin or serum creatinine levels between the groups. Thus, years of poor metabolic control, drastically improved, preceded the development of irreversible severe retinopathy in these young type I IDDM patients.
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| 7. |
- Agardh, Carl-David, et al.
(författare)
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Long-standing hyperglycemia in C57BL/6J mice does not affect retinal glutathione levels or endothelial/pericyte ratio in retinal capillaries
- 2000
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Ingår i: Journal of Diabetes and its Complications. - 1873-460X. ; 14:3, s. 146-153
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Tidskriftsartikel (refereegranskat)abstract
- Free radicals have been suggested to play a role in the development of diabetic retinopathy. The aim of the present study was to examine whether the metabolic perturbations caused by high-fat feeding of two strains of mice, the C57BL6/J mice and the NMRI mice, interfere with one of the free radical enzyme defense systems in the retina, i. e., glutathione (GSH), and whether morphological changes occur in the retinal vessels. C57BL/6J mice and NMRI mice were fed a high-fat diet (55%) for 18 months. High-fat fed mice of both strains developed overweight, hyperinsulinemia, and hyperlipidemia. In addition, the high-fat fed C57BL/6J mice also developed sustained hyperglycemia for at least 15 months. The C57BL/6J mice had lower retinal GSH levels than the NMRI mice, both when given a normal diet (29.6+/-1.2 vs. 37.1+/-1.4 nmol/mg protein; p<0.01) and when given a high-fat diet (27.0+/-1.6 vs. 34.7+/-2.6 nmol/mg protein; p<0.05). Despite the long-standing hyperglycemia, hyperinsulinemia and hyperlipidemia in the C57BL/6J mice, high-fat feeding did not cause any changes in the retinal tissue levels of GSH (27.0+/-1.6 vs. 29. 6+/-1.2 nmol/mg protein) or cysteine (7.61+/-0.63 vs. 6.80+/-0.59 nmol/mg protein). Similarly, high-fat feeding did not affect retinal GSH or cysteine levels in NMRI mice. No light microscopical retinal vessel changes were seen, either in C57BL/6J or in NMRI mice. The study therefore shows that long-standing metabolic perturbations induced by dietary obesity do not induce signs of retinopathy in two different strains of mice. Further studies are needed to explore whether this is explained by increased expression of protecting systems making these strains of mice resistant to effects of oxidative stress.
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| 10. |
- Anderzen, J., et al.
(författare)
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Teenagers with poor metabolic control already have a higher risk of microvascular complications as young adults
- 2016
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Ingår i: Journal of Diabetes and Its Complications. - : Elsevier BV. - 1056-8727 .- 1873-460X. ; 30:3, s. 533-536
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Tidskriftsartikel (refereegranskat)abstract
- Aims: To evaluate how HbA1c in adolescents with type 1 diabetes affects microvascular complications in young adults. Methods: All individuals registered in the Swedish paediatric diabetes quality registry (SWEDIABKIDS) 13-18 years of age, and as adults registered in the Swedish National Diabetes Registry (NDR) in both the years 2011 and 2012 were included, in total 4250 individuals. Results: Of the individuals with mean HbA1c >78 mmol/mol in SWEDIABKIDS 83.4% had retinopathy, 15.8% had microalbuminuria and 4.9% had macroalbuminuria in NDR. The logistic regression analysis showed that the OR to develop macroalbuminuria as a young adult was significantly higher in the group with mean HbA1c >78 mmol/mol in SWEDIABKIDS (p < 0.05). Among the patients with mean HbA1c above 78 mmol/mol in both registries there was a significantly higher proportion that had retinopathy, microalbuminuria (p < 0.001) and/or macroalbuminuria (p < 0.01) compared to the group with HbA1c below 57 mmol/mol in both registries. Only 6.5% of the persons in this study were over 30 years of age. Conclusions: Paediatric diabetes teams working with teenagers must be aware of the impact of good metabolic control during adolescence, and should intensify the care during this vulnerable period of life to reduce the risk of microvascular complications in young adults.
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