Biomedical subjects

C D Agardh

Publications and source records attributed to C D Agardh.

At least 19 recordsLinked to original sources

PubMed2003

Circulating anti-pericyte autoantibodies are present in Type 2 diabetic patients and are associated with non-proliferative retinopathy.

AIMS/HYPOTHESIS: This study aims to determine the prevalence of anti-pericyte autoantibodies in Type 2 diabetes and to characterize these autoantibodies as new markers of disease activity in diabetic retinopathy. METHODS: A total of 299 patients with Type 2 diabetes participated in this study. Retinopathy was assessed by 7-field stereo fundus photography and was graded according to the ETDRS scale. Serum anti-pericyte autoantibodies were detected by immunofluorescence on tissue cultured bovine retinal pericytes. RESULTS: The prevalence of anti-pericyte autoantibodies in Type 2 diabetic patients was 54% and was approximately equal in men and women. The prevalence was approximately 55% with retinopathy at grades from 10 to 53. At grades above 53 the prevalence declined to 23% ( p<0.0001). The highest prevalence by duration of diabetes, 70%, was found at 0 to 5 years and the lowest, 25% at more than 25 years duration ( p<0.0001). CONCLUSION/INTERPRETATION: Anti-pericyte autoantibodies are present at high prevalence in Type 2 diabetes. Their presence during earlier stages of retinopathy could be due to a reaction with antigens expressed by "activated" pericytes. The decline in antibody prevalence in advanced retinopathy could mark pericyte loss and progression to an angiogenic retinal milieu.

Autoantibodies↗

PubMed2003

Socio-demographic and psychosocial factors are associated with features of the metabolic syndrome. The Women's Health in the Lund Area (WHILA) study.

AIM: The aim was to analyse any associations between socio-demographic and psychosocial factors and different features of the metabolic syndrome in a geographically well-defined population of middle-aged women. METHODS: A population of 10 766 Caucasian women aged 50-59 years was investigated regarding biological and socio-demographic conditions, physical activity, dietary habits, aspects of quality of life, and subjective physical and mental symptoms. The screening instrument was used to discriminate subjects as positive or negative on one or more of a total of eight variables considered to be linked to the metabolic syndrome. The cut-off values for positive screening were non-fasting capillary blood glucose >/= 8.0 mmol/l and serum triglycerides >/= 2.3 mmo/l, BMI >/= 30 kg/m2, WHR >/= 0.90, blood pressure >/= 160 and/or 95 mmHg, a family history of diabetes, and pharmacological treatment for hypertension or hyperlipidaemia. RESULTS: Altogether 6805 women (63.2%) participated: 3535 with positive and 3270 with negative screening. Multiple logistic regression analyses showed that comprehensive (OR 1.62, 95% CI 1.41-1.87) and upper secondary (1.40, 1.24-1.57) school, low physical quality of life (1.41, 1.23-1.61) and high sum of subjective physical symptoms (1.06, 1.04-1.08) were positively associated with one or more features of the metabolic syndrome, while high leisure-time exercise and healthy diet (0.84, 0.71-0.99), and low (</= 83 g/week) (0.71, 0.63-0.81) and moderate (84-167 g/week) (0.78, 0.65-0.93) alcohol consumption were negatively associated. CONCLUSIONS: To identify middle-aged women with cardiovascular risk factors and high risk for diabetes, it is important to consider not only biological, but also socio-demographic and psychosocial conditions.

Alcohol Drinking↗

PubMed2001

A screening procedure detecting high-yield candidates for OGTT. The Women's Health in the Lund Area (WHILA) study: a population based study of middle-aged Swedish women.

The objective was to evaluate a screening procedure for detecting high-yield candidates for an OGTT, in a population of middle-aged Swedish women. A two-step screening procedure was performed in 6917 subjects. Women with a positive screening outcome, i.e. increased non-fasting capillary blood glucose, serum triglycerides, BMI, WHR, blood pressure or a family history of diabetes, pharmacological treatment of hypertension or hyperlipidaemia at the primary screening underwent a 75-g OGTT. A control group of women with negative screening outcome (n = 221) also underwent an OGTT. In 2923 women with positive screening outcome, 517 (17.7%) had NFG/IGT (normal fasting venous blood glucose <5.6 mmol/l and 2h-glucose 6.7-9.9 mmol/l), 109 (3.7%) IFG/IGT (fasting 5.6-6.0 and 2h 6.7-9.9 mmol/l) and 223 (7.6%) diabetes (fasting > or = 6.1 or 2h > or = 10.0 mmol/l). These figures were three, five and four times higher, respectively, than in the control group with negative screening outcome (p < 0.001 for all); no differences were found for IFG/NGT (fasting 5.6-6.0 and normal 2h < 6.7 mmol/l) (4.6% vs. 7.2%). For predicting impaired glucose metabolism (IFG/NGT, NFG/IGT, IFG/IGT, diabetes), the screening instrument showed an estimated sensitivity of 70%, specificity of 55%, positive predictive value of 34% and negative predictive value of 85%, based on findings in the control sample. The odds ratio for NFG/IGT increased with the numbers of risk factors from 2.8 to 7.7, for IFG/ IGT from 5.7 to 55.0 and for diabetes from 2.5 to 18.1. High B-glucose, WHR and BMI were the three most important factors associated with an increased risk for NFG/IGT, IFG/IGT and diabetes. In subjects with IFG/NGT, none of the screening variables was associated with an increased risk. In summary, the results show a population screening method focused on features of the metabolic syndrome that discloses high-yield candidates for OGTT. A high prevalence of unknown impaired glucose metabolism was found in middle-aged women with a positive screening profile.

Analysis of Variance↗

PubMed2001

Classifying diabetes according to the new WHO clinical stages.

AIMS/HYPOTHESIS: To test the usefulness of the new WHO criteria for clinical staging of diabetes in the characterization of 1977 diabetic patients. METHODS: The following clinical stages were used: patients on diet and/or oral antidiabetic agents 2 years after diagnosis were considered as non-insulin requiring (NIR; n = 711) and patients who required insulin therapy after 1 year as insulin requiring for control (IRC; n = 543). Patients who because of deteriorating hyperglycemia within 1 year required insulin therapy were considered as insulin requiring for survival (IRS; n = 743). RESULTS: The NIR patients had the highest age at onset (52 +/- 12 years; mean +/- SD), BMI (29.3 +/- 5.2 kg/m2) and C-peptide concentrations (median 0.98 nmol/l; interquartile range 0.72-1.31 nmol/l) but the lowest frequency of GAD antibodies (5.5%) compared to the IRC and IRS groups. The IRC group had a high age at onset (49 +/- 13 years), BMI (28.0 +/- 4.8 kg/m2), frequency of GAD antibodies (16.8%), intermediate C-peptide concentrations (0.56 nmol/l, interquartile range 0.28 +/- 0.94), and the highest prevalence of nephropathy (31.5%) and neuropathy (68.1%). The IRS group had the lowest age at onset (23 +/- 15 years), BMI (24.2 +/- 3.4 kg/m2), C-peptide concentrations (0.05 nmol/l, interquartile range below detection limit 0.01) and highest frequency of GAD antibodies (44.5%). Retinopathy was more common in IRS than in IRC patients (62.1 vs. 43.9%;p < 0.001). CONCLUSIONS: The new WHO criteria seem to discriminate three distinct subgroups and thus provide a useful tool for clinical staging. The IRC patients seem to have a more severe disease than the IRS patients, which has not been clearly acknowledged in the etiological classification. However, because of the cross-sectional nature of these data, they need to be confirmed in a prospective study with defined cut-off limits for when insulin should be initiated.

Aged↗

PubMed2001

Retinal glial cell immunoreactivity and neuronal cell changes in rats with STZ-induced diabetes.

PURPOSE: To study whether diabetes could influence glial cells, retinal neurons, and pigment epithelial cells and if so, to evaluate whether any changes could be influenced by aminoguanidine (AG) or probucol (PB). METHODS: Streptozocin (STZ)-induced diabetic male Wistar rats and age-matched control rats were fed a normal diet, addition of AG in the drinking water (0.5 g/l for diabetic and 1.0 g/l for control rats) or PB in the pellets (1 % w/w) for one or six months. Paraffin embedded retinal sections were incubated in the primary antibodies GFAP, calbindin, RPE65, and Hu, for glial, horizontal, pigment epithelial, and ganglion cells, respectively, and in fluorescent secondary antibodies. RESULTS: One month after STZ injection, GFAP immunoreactivity was sparse, but after six months it was prominent in glial cells in 5/5 diabetic and 1/7 control retinas (p = 0.015). Neither AG, nor PB influenced this immunoreactivity. Numbers of retinal pigment epithelial cells and cells in the ganglion cell layer, were similar at one and six months of diabetes. By time, the number of horizontal cells decreased (p < 0.001) and branching and numbers of their terminals were reduced (p < 0.001). CONCLUSION: Diabetes for six months resulted in increased glial cell immunoreactivity, and by age, horizontal cell numbers and branching of their terminals decreased, morphological patterns that were unaffected by AG or PB. The numbers of retinal pigment epithelial cells and cells in the ganglion cell layer were unaffected both by age and diabetes.

Animals↗

PubMed2000

Effects of norethisterone acetate addition to estradiol in long term HRT.

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

Administration, Cutaneous↗

PubMed2000

Fetal growth is not associated with early onset of severe retinopathy in type 1 diabetes mellitus.

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.

Adult↗

PubMed2000

Direct medical costs for patients with type 2 diabetes in Sweden.

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.

Adult↗

PubMed2000

Severe retinopathy in type 1 diabetic patients is not related to the level of plasma homocysteine.

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.

Adult↗

PubMed1999

[Health economics analysis of diabetes is necessary. It facilitates decision-making and international comparison].

Cost-of-illness studies have shown diabetes to be associated with substantial direct and indirect costs, accounting for 5-6 percent of total health care expenditure. In a Swedish study, where total costs were divided into costs due to management of diabetes and costs due to complications, the total annual cost to the community was estimated to be SEK 5.7 billion in 1994, costs due to complications being the major item, accounting for over 75 per cent of the total. There have been few other Swedish studies of costs for diabetes or diabetes-related complications. The most widely studied category of complications is diabetes-related foot ulcers, with an estimated annual cost of SEK 1-2 billion. However, earlier studies were marred by shortcomings: costs estimated for the main diagnosis only, without breakdown into categories or distinction between type 1 and type 2 diabetes, sources of data other than official data-bases ignored, etc. Diabetes care in Sweden is of high quality, and substantial clinical, epidemiological and health economics research has been carried out. It is important that Sweden contributes to international research on health economics aspects of diabetes.

Controlled Clinical Trials as Topic↗

PubMed1999

Individualized low-dose growth hormone (GH) treatment in GH-deficient adults with childhood-onset disease: metabolic effects during fasting and hypoglycemia.

Growth hormone (GH) has insulin-antagonistic effects, and GH secretion is augmented during fasting and hypoglycemia. In the present study, 10 patients aged 21 to 28 years with childhood-onset GH deficiency (GHD) were studied during a 24-hour fast and a hypoglycemic glucose clamp before and after 9 months of GH replacement. During the 24-hour fast, blood glucose, serum insulin, and serum free fatty acid (FFA) levels were measured. In the hypoglycemic clamp, the counterregulatory hormones (plasma catecholamines, serum glucagon, and serum cortisol), serum insulin-like growth factor (IGF) binding protein-1 (IGFBP-1), serum FFA, and glucose uptake were measured. The GH dose was adjusted to the response of serum IGF-I, and the median GH dose was 0.14 IU/kg/wk (range, 0.08 to 0.19). At the end of the study, serum IGF-I levels were normalized in all but one patient, in whom serum IGF-I was above the normal range. Nine months of GH treatment did not cause any significant changes in the blood glucose level, insulin to glucose ratio, or serum FFA level during the 24-hour fast, and none of the patients experienced hypoglycemia either before or after GH treatment. However, GH therapy resulted in increased insulin resistance during hypoglycemia, without changes in the counterregulatory hormonal responses, serum IGFBP-1, or serum FFA.

Adult↗

PubMed1999

The temporal development of retinopathy and nephropathy in type 1 diabetes mellitus during 15 years diabetes duration.

In this prospective study, the 10- and 15-year incidence and course of retinopathy were examined in relation to medical risk indicators from 3.1 +/- 1.9 (mean -/+ SD) years diabetes duration and onwards in 29 adult type 1 diabetic patients treated under routine care. A total of 28 patients were followed for 10 years and 20 patients for 15 years diabetes duration. After 10 years diabetes duration, 11 patients had developed any retinopathy (ten patients background retinopathy and one patient clinically-significant macular oedema). After 15 years diabetes duration, 16 patients had developed any retinopathy (12 patients developed background retinopathy and four patients developed potentially sight-threatening retinopathy, i.e. clinically significant macular oedema (n = 2) or severe non-proliferative retinopathy (n = 2)). None of the patients developed proliferative retinopathy. No differences were seen in mean HbA1c values between patients without any retinopathy and patients with background retinopathy, whereas patients who developed potentially sight-threatening retinopathy had higher mean HbA1c levels than patients without any retinopathy. Patients who developed potentially sight-threatening retinopathy had higher levels of mean HbA1c both after 10 (9.7 +/- 1.6 vs 6.9 +/- 1.5%; P < 0.05) and 15 years diabetes duration (9.3 +/- 1.2 vs 7.1 +/- 1.3%; P < 0.05), compared to patients without any retinopathy. They also had higher levels of mean HbA1c than patients with background retinopathy after 15 years diabetes duration (9.3 +/- 1.2 vs 7.7 +/- 1.1%; P < 0.05). There were no differences in blood pressure levels between patients who developed retinopathy and those who did not. Only two patients developed clinical signs of nephropathy (urinary albumin 320-1590 mg/l) after 12 and 13 years diabetes duration, respectively. At those time points, both patients had already developed background retinopathy since 2 years. In conclusion, the present study shows that the incidence of retinopathy is associated with the duration of diabetes and that there is a strong association between the degree of metabolic control and development of potentially sight-threatening retinopathy. The study also indicates that the development of retinopathy does not seem to be associated with hypertension or clinical signs of nephropathy.

Adult↗

PubMed1999

The effects of tolbutamide on lipoproteins, lipoprotein lipase and hormone-sensitive lipase.

Type 2 diabetic patients are at increased risk to develop atherosclerotic vascular disease. These patients are often treated with sulphonylurea derivatives, and it has been suggested that this treatment might contribute to the increased atherosclerotic process. The aim of the present study was therefore to investigate whether tolbutamide influences lipid metabolism in such a way that the atherosclerotic process may be promoted. Addition of tolbutamide (5-500 mg/l) to isolated rat fat adipocytes inhibited the lipoprotein lipase (LPL) activity in a dose-dependent manner to levels about 50% of those registered in the absence of tolbutamide. This effect was due to inhibition of the activation of the enzyme in the tissue and not to interference with the interaction of enzyme with its substrate. Addition of tolbutamide (500 mg/l) also inhibited noradrenaline (100 nM) and isoprenaline (40 nM)-induced lipolysis by 48.1 +/- 7.4% (mean +/- S.E.M.) and 47.3 +/- 5.5%, respectively. The decreased lipolysis in tolbutamide preincubated adipocytes was shown to be the result of an inhibition of the phosphorylation of hormone sensitive lipase (HSL). Three months of tolbutamide treatment (0.5 g t.i.d.) in diet treated type 2 diabetic patients did not influence the plasma concentrations of cholesterol, triglycerides, LDL cholesterol, HDL cholesterol as well as HDL triglycerides and HDL phospholipids, and there were no differences compared to placebo treated patients. There was a tendency towards a decrement in the elimination rate of exogenous triglycerides in the tolbutamide group (P = 0.0801). No differences between the groups and no treatment effects were seen on LPL and hepatic lipase activities. In conclusion, our in vitro data show that tolbutamide has dual effects on lipid transport, with impairment of the LPL system, which would tend to decrease plasma lipoproteins by reducing hepatic production of lipoproteins. In vivo, these two effects seem to balance each other and plasma lipoprotein levels remain unaffected.

Adipocytes↗

PubMed1999

A study of Tamm-Horsfall protein excretion in hypertensive patients and type 1 diabetic patients.

OBJECTIVE: The study was performed in order to evaluate to what extent hypertension or diabetes mellitus may affect the urinary excretion rate of Tamm-Horsfall protein. MATERIALS AND METHOD: The urinary excretion rates of albumin and Tamm-Horsfall protein, a measure of glomerular and distal tubular function, respectively were measured in patients with essential hypertension (n = 17) and in type 1 diabetes with (n = 20) or without nephropathy (n = 8) and in apparently healthy subjects (n = 10). RESULTS: Mean 24-h ambulatory blood pressure measurements showed higher blood pressure levels in the hypertensive (167/ 106 mmHg, p < 0.001) than in the diabetic patients with (136/84 mmHg) and without nephropathy (121/74 mmHg) and in healthy subjects (122/76 mmHg). Day and night ratios of systolic and diastolic blood pressure levels were not different among the four groups. Urinary albumin excretion rate was increased in patients with hypertension (30.8 x/ 3.4 microg/min; geometric mean x/tolerance factor; p < 0.001) and diabetes with nephropathy (462 x/ 3.5 microg/min; p < 0.001) compared with diabetic patients without nephropathy and healthy subjects (4.6 x/ 1.9 and 3.7 x/ 1.5 microg/min, respectively). The Tamm-Horsfall protein excretion rate was decreased in patients with diabetic nephropathy (11.6 x/ 3.5 microg/min) compared to patients with hypertension (36.3 x/2.1 1g/min; p < 0.01), diabetes without nephropathy (39.2 x/ 2.0 microg/min; p < 0.05) and healthy subjects (63.0 x/ 1.4 microg/min; p < 0.001), whereas no differences were found among the latter three groups. CONCLUSION: These data indicate that high blood pressure may be associated with albuminuria, while a decrease in excretion rate of Tamm-Horsfall protein may be associated with diabetic nephropathy. These associations need to be studied in a larger population.

Aged↗

PubMed1998

Glutathione levels are reduced in diabetic rat retina but are not influenced by ischemia followed by recirculation.

Free radicals have recently been proposed to play a role in the development of diabetic retinopathy. The aim of the present study was to examine whether the abnormal metabolism caused by diabetes and by ischemia followed by recirculation interferes with a free radical enzyme defense system in the retina, ie, glutathione. Diabetes mellitus was induced by injecting streptozotocin ([STZ] 60 mg/kg body weight [BW] intraperitoneally). After 2 and 6 months, respectively, glutathione levels were measured in the retina and compared against those of age-matched normal control rats. Retinal ischemia was induced by careful ligation of the vessels and the accompanying optic nerve behind the left eye bulb. The right eye served as a control. After 90 minutes of ischemia, retinal circulation was reestablished by removing the ligature. Two-month-old diabetic rats were kept for an additional 3 days and normal rats for 5 minutes, 15 minutes, or 3 days before they were killed for measurement of glutathione. Retinal levels of glutathione were significantly lower in 6-month diabetic compared with 2-month diabetic rats (16.6 +/- 2.9 v 19.0 +/- 2.2 nmol/mg protein, P < .05) and 6-month normal control rats (16.6 +/- 2.9 v 21.0 +/- 2.1 nmol/mg protein, P < .001). Ischemia followed by recirculation did not influence the total tissue level of glutathione either in 2-month-old diabetic rats or in normal rats. The present study indicates that the abnormal metabolism caused by diabetes, rather than by changes in retinal circulation, results in an impaired defense mechanism against free radicals, a factor that may be of importance for the development of diabetic retinopathy. However, since glutathione levels in the present study were measured in the whole retina, it cannot be excluded that particular cell types, such as vascular cells, show an alteration in glutathione that is masked by the glutathione levels in the other nonvascular cells of the retina. Studies using other techniques are needed to further explore this subject.

Animals↗

PubMed1998

The incidence of nephropathy in type 1 diabetic patients with proliferative retinopathy: a 10-year follow-up study.

Patients with type 1 diabetes mellitus and with proliferative retinopathy often have a concomitant diabetic nephropathy. However, in cross-sectional studies it has been shown that 35% of patients with proliferative retinopathy do not show signs of diabetic nephropathy. The aim of the present study was to examine the incidence of diabetic nephropathy in type 1 diabetic patients with proliferative retinopathy but without signs of nephropathy. To that end, out of 102 consecutive patients with proliferative retinopathy attending the University Hospital, Lund, in 1986, 24 patients did not show any clinical signs of nephropathy, and were followed for 10 years regarding the development of nephropathy. Their age was 36.7 +/- 9.8 years, age at onset 11.8 +/- 7.5 years, diabetes duration 25.7 +/- 6.9 years and duration of proliferative retinopathy 4.6 +/- 3.8 years (mean +/- S.D.). At entry, no patient had albuminuria (< 30 mg/l), and albumin creatinine clearance ratio was < 0.01 x 10(-3). During the 10-year follow-up period, two of the patients showed isolated higher peaks of elevated urinary albumin, but none of the 24 patients developed persistent microalbuminuria (> or = 30 mg/l). Two patients died before follow-up, but none of these had developed microalbuminuria at the time for death. Based on mean annual measurements, there were no increases in HbA1c, systolic and diastolic blood pressure, and serum creatinine levels. At entry, seven of the patients were treated with antihypertensive drugs and another three patients received such treatment during the study period. In conclusion, in a subgroup of patients with proliferative retinopathy, i.e. without clinical signs of diabetic nephropathy, no patient developed persistent microalbuminuria during a 10-year follow-up period. These results indicate further evidence for at least partly different pathogenic mechanisms behind diabetic retinopathy and nephropathy.

Adult↗

PubMed1998

Inverse relationship between GAD65 antibody levels and severe retinopathy in younger type 1 diabetic patients.

Several risk factors for severe non-proliferative and proliferative retinopathy in type 1 diabetes mellitus have been proposed without explaining the rapid progression of retinopathy in some patients. Since GAD65 autoantibodies (GAD65Abs) are detected against glutamic acid decarboxylase (GAD), which is mainly expressed in islets and nervous tissue in type 1 diabetic patients, the aim of the present investigation was to test the hypothesis whether GAD65Abs are associated with rapidly progressing severe retinopathy. Patients with severe non-proliferative or proliferative retinopathy (n = 27) were compared with another group, which in spite of long diabetes duration had no or only mild signs of retinopathy (n = 28). GAD65Abs were analysed in a radioimmunoassay using in vitro translated human GAD65, and the levels were expressed as an index in relation to positive and negative reference samples. Using a cut-off level representing the 99th percentile of normals, 6/27 (22%) with and 9/28 (32%) without severe retinopathy were considered GAD65Ab positive. Although there was no difference in the number of GAD65Ab positive patients, the GAD65Ab levels were lower in patients with (0.30; 0.11-0.64) than without (0.68; 0.34-1.12) severe retinopathy (P = 0.03). The patients were also subjected to HLA-DR and DQ typing by PCR and hybridization with oligospecific probes. DQ2/8 was more common in patients with (56%) than without (29%) severe retinopathy (P = 0.05), but DQ2/8 could not account for the lower GAD65Ab levels in patients with severe retinopathy. It is concluded that GAD65Ab levels are inversely correlated with severe retinopathy in young type 1 diabetic patients.

Adult↗

PubMed1998

Sustained elevation of cerebral blood flow after hypoglycaemia in normal man.

During hypoglycaemia, counter-regulatory hormones are released, cognitive function is impaired and cerebral blood flow is increased. In the immediate period after normalisation of blood glucose only counter-regulatory hormones seem to be normalised. The aim of this study was to follow the changes in cerebral blood flow during a prolonged recovery period following moderate hypoglycaemia in normal man. In 15 healthy men, hypoglycaemia was induced by an intravenous infusion of insulin (2.5 mU/kg per min) to a blood glucose of 2.2 +/- 0.3 mmol/l (mean +/- S.D.) and was kept at this level for 66 +/- 11 min. The cerebral blood flow was measured by a single photon emission computed tomography camera (SPECT) recording the clearance of intravenously administered xenon-133. Measurements were performed before, at the beginning and at the end of the hypoglycaemic period, as well as 23 +/- 5, 51 +/- 7 and 97 +/- 7 min after normalisation of the blood glucose. The basal cerebral blood flow was 50.2 +/- 5.2 ml/100 g per min, increased to 55.6 +/- 4.9 ml/100 g per min (P < 0.001) during hypoglycaemia, and remained at this level at all measurements after normalisation of blood glucose. There was no relation between the rate of fall in blood glucose or level of hypoglycaemia and increment in cerebral blood flow or the actual blood flow during hypoglycaemia. The values of plasma adrenaline, serum ACTH, serum cortisol and symptom scores increased significantly during hypoglycaemia. The adrenaline level was back to the basal level at the first measurement after normalisation of blood glucose, while the ACTH level was normalised at the subsequent measurement and the cortisol level at the last measurement. In conclusion, the results show that despite normalisation of counter-regulatory hormones and hypoglycaemic symptoms, the cerebral blood flow remains elevated for at least 97 +/- 7 min following 66 +/- 11 min of moderate hypoglycaemia, indicating that additional factors which are not coupled to the cerebral metabolism influence this vasculatory response.

Adrenocorticotropic Hormone↗