| 1. |
- 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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| 2. |
- Agardh, Elisabet, et al.
(författare)
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Effects of inhibition of glycation and oxidative stress on the development of cataract and retinal vessel abnormalities in diabetic rats
- 2000
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Ingår i: Current Eye Research. - 0271-3683. ; 21:1, s. 543-549
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To study effects of inhibition of glycation, and oxidative stress on the development of cataract and retinal vessel abnormalities in diabetic rats. METHODS: Diabetes was induced in male Wistar rats with streptozocin (STZ; 60 mg/kg BW, i.p.). Diabetic as well as strain matched control rats were fed 1) a normal diet, 2) addition of aminoguanidine in the drinking water (0.5 g/l for diabetic rats and 1.0 g/l for control rats) or 3) probucol in the pellets (1% w/w). After 6 months, the number of acellular vessels, endothelial cells and pericytes were counted in trypsin digested retinal vessel preparations, and the total retinal tissue amount of glutathione (GSH) and cysteine was measured with HPLC. RESULTS: Cataract formation occurred after 13 weeks in diabetic animals compared with 17 weeks for those treated with aminoguanidine, and 16 weeks for those treated with probucol (p < 0.001 in both cases). Aminoguanidine inhibited the formation of acellular collapsed capillary strands, 9 (3-14) vs. 18 (12-262) (median, range) per quadrant in untreated diabetic rats (p = 0.004), while probucol did not have any effect. Neither aminoguanidine, nor probucol influenced the endothelial/pericyte ratio. Diabetes caused a reduction in the GSH/cysteine ratio (10.7 +/- 0.6 vs. 15.3 +/- 1. 5) (mean +/- SD; p < 0.001). Probucol partly restored this imbalance (p < 0.05) whereas aminoguanidine did not. CONCLUSIONS: The results indicate that cataract formation in diabetes involves both glycation and oxidative stress processes. The reduced formation of acellular collapsed capillary strands by aminoguanidine suggests a potential role for glycation in vascular damage. The positive effect of probucol on cysteine/GSH metabolism imbalance indicates that derangements of one of the retinal defense systems against oxidative stress can be normalized by antioxidants.
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| 3. |
- Agardh, Elisabet, et al.
(författare)
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Fetal growth is not associated with early onset of severe retinopathy in type 1 diabetes mellitus
- 2000
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Ingår i: Diabetes Research and Clinical Practice. - 1872-8227. ; 48:1, s. 61-65
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Tidskriftsartikel (refereegranskat)abstract
- Reduced fetal growth has been suggested as a possible risk factor for diabetic nephropathy. The aim of the present study was to examine whether there could be an association also with rapidly progressing severe retinopathy in younger type 1 diabetic patients. Maternal pregnancy, as well as birth parameters of 27 type 1 diabetic patients with severe retinopathy diagnosis at a median age of 25 years, were studied retrospectively. The control group consisted of 22 type 1 diabetic patients with mild background retinopathy and with similar age, age at onset, and duration of diabetes. Mothers of the subjects with severe retinopathy had a higher body mass index (P = 0.03) but similar age, blood pressure levels, and weight gain during pregnancy as those of the control group. All but four babies, two in each group, were born after 37 completed gestational weeks. There were no differences regarding birth weight or of relative birth weight corrected for gestational length. Head circumference, birth length, and placenta weight were similar. The results indicate that fetal growth is not a factor of major importance for the development of severe retinopathy in younger type 1 diabetic patients.
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| 4. |
- Agardh, Elisabet, et al.
(författare)
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Severe retinopathy in type 1 diabetic patients is not related to the level of plasma homocysteine
- 2000
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Ingår i: Scandinavian Journal of Clinical & Laboratory Investigation. - : Informa UK Limited. - 1502-7686 .- 0036-5513. ; 60:3, s. 169-174
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Tidskriftsartikel (refereegranskat)abstract
- The vascular-injuring amino acid homocysteine was previously shown to be increased in plasma in type 1 diabetic patients with clinical signs of nephropathy. Previous studies have also shown an inconsistent relationship between the development of diabetic nephropathy and retinopathy, indicating different pathogenetic mechanisms. In this study, plasma homocysteine was measured in 25 type 1 diabetic patients with a well-characterized form of severe retinopathy. Furthermore, a group of 24 type 1 diabetic patients with similar age at onset of diabetes and diabetes duration with no or minimal background retinopathy were investigated, in order to determine whether plasma homocysteine levels are different from those in patients with severe retinopathy. Patients with severe retinopathy did not have higher plasma levels of homocysteine (13.9 micromol/L; 5.9-30.7, median and range) than those without retinopathy (10.4 micromol/L; 5.7-18.9). Within the group of patients with severe retinopathy, increased homocysteine levels were confined to the patients (19.9 micromol/L; 10.0-30.7, n=9) with serum creatinine levels > 100 micromol/L, compared to those patients (9.6; 5.9-14.3 micromol/L, n=15) with a serum creatinine below 100 micromol/L. None of the patients without or with minimal background retinopathy had serum creatinine levels > 100 micromol/L. We conclude that diabetic retinopathy is not associated with increased plasma homocysteine levels, but plasma homocysteine accumulates, probably owing to reduced glomerular filtration, in diabetic patients with signs of nephropathy. In these patients, the promoting effect of nephropathy on the development of retinopathy does not seem to be mediated through homocysteine.
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| 5. |
- Henriksson, F, et al.
(författare)
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Direct medical costs for patients with type 2 diabetes in Sweden
- 2000
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Ingår i: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 248, s. 387-
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To estimate the total direct medical costs to society for patients with type 2 diabetes in Sweden and to investigate how different factors, for example diabetic late complications, affect costs. DESIGN: Cross-sectional data regarding health care utilization, clinical characteristics and quality of life, were collected at a single time-point. Data on resource use cover the 6-month period prior to this time point. SETTING: Patient recruitment and data collection were performed in nine primary care centres in three main regions in Sweden. SUBJECTS: Only patients with an age at diabetes diagnosis >/= 30 years (type 2 diabetes) were included (n = 777). RESULTS: The total annual direct medical costs for the Swedish diabetes type 2 population were estimated at about 7 billion SEK (Swedish Kronor) in 1998 prices, which is about 6% of the total health care expenditures and more than four times higher than the former Swedish estimate obtained when using diabetes as main diagnosis for calculating costs. The annual per patient cost was about 25 000 SEK. The largest share of this cost was hospital inpatient care. Costs increased with diabetes duration and were higher for patients treated with insulin compared to those treated with oral hypoglycaemic drugs or with life style modification only. Patients with both macro- and microvascular complications had more than three times higher costs compared with patients without such complications. CONCLUSIONS: Type 2 diabetes is a serious and expensive disease and the key to reducing costs seems to be intensive management and control in order to prevent and delay the associated late complications.
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| 6. |
- Li, Cairu, et al.
(författare)
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Effects of norethisterone acetate addition to estradiol in long term HRT
- 2000
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Ingår i: Maturitas. - 1873-4111. ; 36:2, s. 139-152
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The aim of this study was to evaluate the efficacy and tolerability of hormone replacement therapy (HRT) among postmenopausal women living in the Lund area of Southern Sweden and to analyze treatment effects in different types or routes of HRT administration, as well as to compare with unopposed estrogen therapy. METHOD: in an ongoing, large population-based, prospective cohort study, this interim analysis included 3900 women. Of them, 693 postmenopausal women were eligible in the present analyses as they continued to use one of the four commercial HRT products for at least 2-3 years, i.e. continuous oral estradiol (E(2)) 2 mg+norethisterone acetate (NETA) 1 mg (CON-O), sequential oral estradiol 2 mg + norethisterone acetate 1 mg (CYC-O), sequential transdermal estradiol 50 microg + norethisterone acetate 250 microg (CYC-TRANS) and estradiol monotherapy. These women completed one generic questionnaire and one specific 'hormonal' questionnaire, as well as a personal interview pertaining to socio-demographics, detailed status of HRT use, and therapeutic efficacy and untoward side-effects by HRT. RESULTS: comparing the three combined E(2)+NETA groups with E(2) monotherapy, the beneficial effects on sexual desire and emotional well-being were significantly less in the combined groups than in E(2) monotherapy group. There was no significant difference regarding the negative side-effects between the groups. No significant difference was found between CON-O and CYC-O groups either in positive effects or in negative side-effects. A higher prevalence of positive effects was found in CYC-TRANS group than that in CYC-O group, especially in amelioration of sleep and urinary symptoms. Higher odd ratios of negative effects by HRT, such as irregular bleeds, weight gain, food craving and skin disorders were also found in CYC-TRANS group. CONCLUSION: in long-term HRT administration, the addition of a progestogen in HRT could compromise the beneficial effects of estradiol, particularly, the effects on women's emotional well being and psychosexual functioning. Administration of NETA continuously and sequentially had similar therapeutic efficacy and tolerability. More marked positive effects, such as improving of sleep and urinary symptoms, as well as nuisance side-effects, i.e. irregular bleeds, weight gain, food craving and skin disorders were encountered by the women using sequential transdermal regimen
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| 7. |
- Li, Cairu, et al.
(författare)
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Important factors for use of hormone replacement therapy: a population-based study of Swedish women. The Women's Health in Lund Area (WHILA) Study
- 2000
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Ingår i: Menopause. - 1530-0374. ; 7:4, s. 273-281
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The aim of this study was to delineate the use of hormone replacement therapy (HRT) among women who were born between December 2, 1935, and December 1, 1945, and living in the Lund area of southern Sweden and to analyze factors that contribute to the acceptance and continuation of HRT. METHODS: All women received a generic questionnaire pertaining to demographic background, lifestyle, health behavior, and climacteric symptoms and underwent a personal interview. An interim analysis was carried out on 3,900 women. We mailed a hormone questionnaire to the women who were using HRT (n = 1,875). This hormone questionnaire covered, for example, menopausal status, complaints, and alterations in and efficacy of HRT use, as well as the reasons for discontinuing HRT use. RESULTS: A total of 1,415 (76%) women answered the hormone questionnaire. Forty-eight percent were HRT ever users, and 32% were current users. Mean duration of HRT use was 47 months. The most common incentives for HRT use were alleviation of menopausal symptoms (72%) and prevention of bone loss (50%) and/or cardiovascular disease (31%). Forty-seven percent of HRT users reported that they had changed regimens at least once. HRT users had higher education, full-time work, and a higher consumption of alcohol but less consumption of cigarettes. They reported higher frequencies of climacteric symptoms, past histories of premenstrual syndrome, use of oral contraceptives, and hysterectomy. They also had a higher consumption of healthcare resources. A total of 177 women withdrew from therapy. The most common reasons for discontinuation of HRT were weight gain, anxiety of cancer, bleeding, breast tenderness, and emotional problems. Compared with current users, past users had less positive as well as fewer negative effects of HRT. Several variables contributed to compliance, including education, full-time work, regular exercise, low frequency of persistent climacteric symptoms, and alteration of regimens. CONCLUSION: Education, working conditions, lifestyle, interest in prevention, and severity of the climacteric symptoms are determinants for both acceptance of and compliance with HRT.
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| 8. |
- Torffvit, Ole, et al.
(författare)
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The prognosis for type 2 diabetic patients with heart disease. A 10-year observation study of 385 patients
- 2000
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Ingår i: Journal of Diabetes and its Complications. - 1873-460X. ; 14:6, s. 301-306
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Tidskriftsartikel (refereegranskat)abstract
- The objective was to study the development and progression of heart disease in type 2 diabetic patients and to evaluate the influence of revascularisation procedures on its outcome. A 10-year observation study in 385 patients attending a hospital-based outpatient clinic was performed. A total of 156/385 patients developed myocardial infarction (n=68), angina (n=44), heart failure (n=34) or died (n=109). A high mortality was seen in patients with myocardial infarction (73%) and heart failure (71%), in contrast, to patients with angina (25%). Thirty patients had a coronary angiography because of angina, out of which 23 were revascularised. Four (17%) of patients with bypass surgery or angioplasty died compared with 57 (67%) of the patients with no intervention (p<0.001). The occurrence of myocardial infarction was associated with age (p<0.0001), and mean systolic (p<0.05) and diastolic (p<0.05) blood pressure and degree of albuminuria at entry (p<0.05). Heart failure was associated with age (p<0.0001), and mean HbA(1c) levels (p<0.05), while angina was associated with age only (p<0.05). Death was associated with age (p<0.0001), diabetes duration (p<0.05), mean diastolic blood pressure (p<0.05), and degree of albuminuria at entry (p<0.0001). This study shows a high incidence of heart disease in patients with type 2 diabetes. The prognosis was better in patients who had had a revascularisation procedure. Thus, a more active attitude towards revascularisation may potentially improve the prognosis for type 2 diabetic patients with atherosclerotic heart disease.
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