Does educational mobility in mid-life affect mortality? A cohort study covering 1.3 million individuals in Sweden.

•Studies on how increased formal educational level in mid-life affects mortality is lacking.•We found that women who increased their educational level in mid-life had a reduced risk of mortality.•In men, mortality was reduced only for those who increased their education from a low level.

Cannabis Use as Risk or Protection for Type 2 Diabetes: A Longitudinal Study of 18 000 Swedish Men and Women.

Aims. Whether or not cannabis use may increase or decrease the risk of type 2 diabetes is not clear. We analyzed the association between cannabis and subsequent type 2 diabetes and if a potential positive or reverse association persisted after controlling for potential confounders. Methods. In this population-based cohort study, 17,967 Swedish men and women (aged 18-84 years), who answered an extensive questionnaire in 2002 (including questions on cannabis use), were followed up for new cases of type 2 diabetes (n = 608) by questionnaire (in 2010) and in health registers during 2003-2011. Odds ratios (ORs) with 95% CIs were estimated in a multiple logistic regression analysis. Potential confounders included age, sex, BMI, physical inactivity, smoking, alcohol use, and occupational position. Results. The crude association showed that cannabis users had a reduced risk of type 2 diabetes OR = 0.68 (95% CIs: 0.47-0.99). However, this inverse association attenuated to OR = 0.94 (95% CIs: 0.63-1.39) after adjusting for age. Conclusions. The present study suggests that there is no association between cannabis use and subsequent type 2 diabetes after controlling for age. To make more robust conclusions prospective studies, with longer periods of follow-up and more detailed information about cannabis use, are needed.

Socio-economic position at three points in life in association with type 2 diabetes and impaired glucose tolerance in middle-aged Swedish men and women.

BACKGROUND: It has been suggested that low socio-economic position (SEP) during childhood and adolescence predicts risk of adult type 2 diabetes. We investigated the associations between type 2 diabetes and childhood SEP (fathers' occupational position), participants' education and adult SEP (participants' occupational position). To determine possible independent associations between early SEP (fathers' occupational position and participants' education) and disease, we adjusted for adult SEP and factors present in adult life associated with type 2 diabetes. METHODS: This cross-sectional study comprised 3128 men and 4821 women aged 35-56 years. All subjects have gone through a health examination and answered a questionnaire on lifestyle factors. At the health centre, an oral glucose tolerance test was administered and identified 55 men and 52 women with previously undiagnosed type 2 diabetes. Relative risks (RRs) with 95% CIs were calculated in multiple logistic regression analyses. RESULTS: The age-adjusted RRs of type 2 diabetes if having a father with middle occupational position were 2.3 [Confidence interval (CI:1.0-5.1) for women and, 2.0 (CI:0.7-5.6) for men]. Moreover, low education was associated with type 2 diabetes in women, RR = 2.5 (CI:1.2-4.9). Low occupational position in adulthood was associated with type 2 diabetes in women, RR = 2.7 (CI:1.3-5.9) and men, RR = 2.9 (CI:1.5-5.7). The associations between early SEP and type 2 diabetes disappeared after adjustment for adult SEP and factors associated with type 2 diabetes. CONCLUSION: The association between type 2 diabetes and low SEP during childhood and adolescence in middle-aged Swedish subjects disappeared after adjustment for adult SEP and adult risk factors of diabetes.

The impact of family history of diabetes and lifestyle factors on abnormal glucose regulation in middle-aged Swedish men and women.

AIMS/HYPOTHESIS: We investigated associations between abnormal glucose regulation and family history of diabetes, separately and in combination with lifestyle risk factors. SUBJECTS AND METHODS: This cross-sectional study comprised 3,128 men and 4,821 women, aged 35-56 years, half with a family history of diabetes. Oral glucose tolerance testing identified subjects with previously undiagnosed prediabetes (IFG, IGT) and type 2 diabetes. Information on lifestyle factors was obtained by questionnaire. Biological interaction was measured with the synergy index. RESULTS: A family history of diabetes conferred a higher odds ratio (OR) for type 2 diabetes in men (OR=3.1, 95% CI 1.7-5.6) than in women (OR=1.7, 95% CI 1.0-3.0), and the synergy index was 2.8 (95% CI 0.9-9.0), suggesting interaction between a family history of diabetes and sex. For prediabetes and diabetes combined, the synergy index was 1.7 (1.0-2.8). Exposure to only one lifestyle risk factor (obesity, physical inactivity, smoking or low sense of coherence [a psychosocial index]) increased the risk to a similar extent in men and women. Combined exposure to a family history of diabetes and lifestyle-related risk factors had a greater effect on type 2 diabetes than any of these factors alone, especially in men. However, analysis of interaction between a family history of diabetes and the lifestyle factors did not indicate any interaction for diabetes, but did indicate interaction for a family history of diabetes and obesity in women with prediabetes. CONCLUSIONS/INTERPRETATION: Our data suggest a more pronounced effect of a family history of diabetes on the risk of type 2 diabetes in men than in women. While both a family history of diabetes and lifestyle risk factors had effects on type 2 diabetes, irrespective of sex, these effects did not appear to interact.

The -374 T/A polymorphism in the gene encoding RAGE is associated with diabetic nephropathy and retinopathy in type 1 diabetic patients.

AIMS/HYPOTHESIS: The receptor for AGE (RAGE) is considered to be mainly an intracellular signal-transducer or pro-inflammatory peptide of possible importance for inflammation and autoimmune diseases. Our aim was to study whether the -374 T/A polymorphism in the gene encoding RAGE (AGER) is associated with diabetes type and presence of diabetic complications. METHODS: The AGER -374 T/A polymorphism was genotyped in 867 type 1 diabetic patients, 2,467 type 2 diabetic patients and 205 non-diabetic control subjects of Scandinavian origin. RESULTS: AGER polymorphism was related to different HLA-DQB1 genotypes and the presence of diabetic complications. Type 1 diabetic patients had a higher frequency of the AGER -374 A/A or T/A genotypes than type 2 diabetic patients (51.1 vs 44.9%, p=0.002) and control subjects (51.1 vs 47.6%, p=0.0006). The RAGE -374 T/A polymorphism was associated with HLA-DQB1 genotypes; patients with HLA risk genotypes had a higher frequency of the A/A or T/A genotypes than patients with other HLA-DQB1 genotypes (60.3 vs 40.3%, p<0.000001). In type 1 diabetic patients, the frequency of the A/A or T/A genotypes was higher in patients with diabetic nephropathy than without (61.1 vs 46.8%, p=0.006) and with sight-threatening retinopathy than without (56.1 vs 47.6%, p=0.03). In type 2 diabetic patients with HbA(1c) values below the median, the T/T genotype was more frequent in patients with diabetic nephropathy than without (54.3 vs 38.2%, p=0.02). CONCLUSIONS/INTERPRETATION: Our results show an association between the AGER -374 T/A polymorphism and type 1 diabetes. This association was HLA-DQB1-dependent. The polymorphism was associated with diabetic nephropathy in both type 1 and type 2 diabetes, in an HbA(1c)-dependent manner in the latter group, and also with sight-threatening retinopathy in type 1 diabetic patients.

Visual acuity and perimetry as measures of visual function in diabetic macular oedema.

AIMS/HYPOTHESIS: We examined to what extent visual acuity and perimetric sensitivity as measures of central and paracentral visual function would be useful for evaluating the presence and severity of diabetic macular oedema. MATERIALS AND METHODS: We evaluated 59 eyes of 59 diabetic patients by identifying the presence (n=20) or absence (n=39) of macular oedema on stereo fundus photographs. The area of oedema and its distance to the centre of the macula were measured. Ischaemic macular damage was quantified by measuring the foveal avascular zone and adjacent perifoveolar intercapillary areas on fluorescein angiograms. Visual function was assessed by visual acuity charts and by short-wavelength perimetry and standard white-on-white perimetry of the central 10 degrees field. RESULTS: Visual acuity did not differ between eyes with and without macular oedema. In eyes with oedema, visual acuity was correlated to the distance of the oedema from the centre of the macula (log of minimum angle of resolution {LogMar} score decreased by 0.15/mm; p=0.006) and to the thickness of the retina when the centre was affected (LogMar score decreased by 0.003/mum of thickness; p=0.0002). Multivariate analyses confirmed the results (R (2)=0.46 and 0.77, respectively). Short-wavelength perimetry sensitivity was more depressed in eyes with oedema (p=0.033) but was not significantly associated with the presence of oedema after correction for macular ischaemic damage. There was no correlation between these field defects and the severity of oedema. CONCLUSIONS/INTERPRETATION: Visual acuity was a useful measure of visual function in diabetic macular oedema involving the centre. Visual field defects were more common in eyes with macular oedema but reflected ischaemic damage of the macula rather than macular oedema itself.

Visual fields correlate better than visual acuity to severity of diabetic retinopathy.

AIMS/HYPOTHESIS: We compared the outcomes of perimetric and visual acuity tests in patients with diabetic retinopathy. METHODS: We examined 59 diabetic patients with different degrees of retinopathy using stereo fundus photography in accordance with the Early Treatment of Diabetic Retinopathy Study (ETDRS) and fluorescein angiography. Conventional white-on-white perimetry (WWP) and short wavelength automated perimetry (SWAP) were performed and analysed with reference to normal values. Visual acuity was measured with ETDRS charts. RESULTS: Regression analysis revealed that visual acuity was significantly associated with increasing severity of retinopathy according to the ETDRS scale when visual acuity was estimated by counting logarithm of minimum angle of resolution (LogMar) scores, but not when visual acuity was measured by the conventional reading of the smallest line that could be seen. Visual acuity decreased by 0.02 LogMar per ETDRS step (p=0.03). The degree of visual field loss was significantly associated with increasing severity of retinopathy according to the ETDRS scale, perimetric sensitivity decreasing by 0.44 dB per ETDRS step (p=0.0001) using WWP, and by 0.40 dB per ETDRS step (p=0.04) with SWAP. The size of the area of the foveal avascular zone and adjacent perifoveal intercapillary areas (PIAs) also affected the central visual field as obtained both by WWP (-2.6 dB/mm2, p=0.03), and by SWAP (-7.9 dB/mm2, p=0.002), but did not affect visual acuity. The regression model fit for peripheral retinopathy according to the ETDRS scale was better using WWP than SWAP or visual acuity, while SWAP testing was superior to both WWP and visual acuity when measuring effects caused by enlarged foveal avascular zones and PIAs. CONCLUSIONS/INTERPRETATION: Perimetry can provide more useful information than visual acuity on functional loss in diabetic retinopathy, particularly when the perifoveal capillary network is damaged.

Nephropathy, but not retinopathy, is associated with the development of heart disease in Type 1 diabetes: a 12-year observation study of 462 patients.

AIMS: To study the occurrence of heart disease and death in Type 1 diabetic patients and evaluate whether presence of microangiopathy, i.e. nephropathy and retinopathy, was associated with the outcome. METHODS: A 12-year observation study of 462 Type 1 diabetic patients without a previous history of heart disease at baseline who were treated under routine care in a hospital out-patient clinic. RESULTS: A total of 85 patients developed signs of heart disease, i.e. myocardial infarction (n = 41), angina (n = 23), and heart failure (n = 17) and 56 patients died. The mortality for patients without signs of heart disease during the observation period was 7.6% compared with 51% in patients with myocardial infarction (P < 0.001), 26% in patients with angina (P < 0.01) and 65% in patients with heart failure (P < 0.001). The relative risk for death was 9.0 (P < 0.001) and 2.5 (P < 0.05) times higher in patients with macroalbuminuria and microalbuminuria, respectively. The risk for cardiovascular death was 18.3 times (P < 0.001) higher in patients with macroalbuminuria compared with patients with normoalbuminuria. In patients with sight-threatening retinopathy, the relative risk for death was 7.0 times higher (P < 0.01) and the risk for coronary heart disease events 4.4 times higher (P < 0.05) compared with patients with no retinopathy. However, when retinopathy was adjusted for presence of macroalbuminuria, this association disappeared. CONCLUSION: This study shows a high incidence of heart disease in patients with Type 1 diabetes. The worse prognosis was seen in patients with sight-threatening retinopathy and macroalbuminuria and microalbuminuria at baseline. Macroalbuminuria and microalbuminuria were independently associated with a high risk for heart disease and death while the association with sight-threatening retinopathy only occurred in the presence of nephropathy.

Coffee consumption, type 2 diabetes and impaired glucose tolerance in Swedish men and women.

OBJECTIVES: The association between coffee consumption, type 2 diabetes and impaired glucose tolerance was examined. In addition, indicators of insulin sensitivity and beta-cell function according to homeostasis model assessment were studied in relation to coffee consumption. DESIGN: Population-based cross-sectional study. SETTING AND SUBJECTS: The study comprised 7949 healthy Swedish subjects aged 35-56 years residing within five municipalities of Stockholm. An oral glucose tolerance test identified 55 men and 52 women with previously undiagnosed type 2 diabetes and 172 men and 167 women with impaired glucose tolerance. Information about coffee consumption and other factors was obtained by questionnaire. RESULTS: The relative risks (adjusted for potential confounders) of type 2 diabetes and impaired glucose tolerance when drinking >/=5 cups of coffee per day compared with /=5 cups day(-1)) was inversely associated with insulin resistance. In addition, in those with type 2 diabetes and in women (not in men) with impaired glucose tolerance high coffee consumption was inversely associated with low beta-cell function. In women, but not obviously in men, with normal glucose tolerance, coffee consumption was associated with a reduced risk of insulin resistance. CONCLUSIONS: The results of this study indicated that high consumers of coffee have a reduced risk of type 2 diabetes and impaired glucose tolerance. The beneficial effects may involve both improved insulin sensitivity and enhanced insulin response.

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.

Diabetic retinopathy, visual acuity, and medical risk indicators: a continuous 10-year follow-up study in Type 1 diabetic patients under routine care.

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.

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.

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.

Effects of inhibition of glycation and oxidative stress on the development of cataract and retinal vessel abnormalities in diabetic rats.

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.

Long-standing hyperglycemia in C57BL/6J mice does not affect retinal glutathione levels or endothelial/pericyte ratio in retinal capillaries.

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.

Screening and prevention of diabetic blindness.

Diabetic eye disease remains a major cause of blindness in the world. Laser treatment for proliferative diabetic retinopathy and diabetic macular edema became available more than two decades ago. The outcome of treatment depends on the timing of laser treatment. The laser treatment is optimally delivered when high-risk characteristics have developed in proliferative retinopathy or diabetic macular edema and before this has significantly affected vision. Laser treatment is usually successful if applied during this optimal period whereas the treatment benefit falls sharply if the treatment is applied too late. In order to optimize the timing of laser treatment in diabetic eye disease screening programs have been established. The oldest screening program is 20 years old and several programs have been established during the last decade. In this paper the organisation and methods of screening programs are described including direct and photographic screening. The incidence and prevalence of blindness is much lower in populations where screening for diabetic eye disease has been established compared to diabetic populations without screening. Technical advantages may allow increased efficiency and telescreening. From a public health standpoint screening for diabetic eye disease is one of the most cost effective health procedures available. Diabetic eye disease can be prevented using existing technology and the cost involved is many times less than the cost of diabetic blindness.

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.

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.

Contrast sensitivity and visual recovery time in diabetic patients treated with panretinal photocoagulation.

PURPOSE: To study patients treated with panretinal photocoagulation regarding contrast sensitivity and visual recovery time after exposure to glare. METHODS: To compare contrast sensitivity and visual recovery-time after exposure to glare in eyes (n=20) from 20 type 1 diabetic patients treated with panretinal photocoagulation for proliferative retinopathy with eyes (n= 19) from 19 un-treated type 1 diabetic patients. Contrast sensitivity was tested with a low contrast acuity chart, before and during exposure to either a uniform background illumination or a spotlight. Visual recovery time was defined as the time required to regain baseline visual acuity during light exposure. RESULTS: Contrast thresholds values were higher in eyes treated with panretinal photocoagulation compared to un-treated eyes before illumination 4.2 +/- 1.2% vs. 3.1 +/- 1.7% (p=0.006), during background illumination 5.8 +/- 5.1% vs. 3.9 +/- 4.8% (p=0.001), and during spotlight exposure 5.6 +/- 2.2% vs. 3.2 +/- 1.8% (p<0.001). Furthermore, recovery time was longer both during background illumination, 20; 5-50 sec vs. 2; 2-80 sec. (md;range), (p<0.001) and during spotlight illumination 27; 5-70 sec vs. 2;1-60 sec. (md;range) (p<0.001). CONCLUSION: Eyes treated with panretinal photocoagulation had higher contrast threshold levels at baseline and during glare, as well as a prolonged visual recovery time compared to un-treated eyes with mild background retinopathy.

Photocoagulation of diabetic macular oedema--complications and visual outcome.

PURPOSE: To describe complications and visual outcome of photocoagulation for clinically significant macular oedema. SUBJECTS AND METHODS: Evaluation of macular oedema and complications of photocoagulation in 194 eyes, defined as subretinal fibrosis, atrophic creep of the pigment epithelium and subretinal neovascularization was based on stereo fundus photo grading. The study included 25 patients with type 1 and 93 patients with type 2 diabetes (age 32 +/- 10 and 65 +/- 9 years, respectively). The statistical evaluations were based on one eye per patient. RESULTS: Follow-up time was 5.5 +/- 2.4 years (mean +/- SD). Complications within 1/3 ODD from the centre of the macula were seen in 4% (1/23) of eyes of patients with type 1 diabetes, compared to 26% (20/76) of eyes among patients with type 2 diabetes (p=0.02). Hard exsudates before treatment were more common in type 2 than in type 1 diabetic eyes, 70/82 vs. 11/23 (p<0.001). In all eyes, hard exsudates were more often associated with subretinal fibrosis or atrophic creep (35/133 eyes) than diffuse oedema (5/44 eyes) (p=0.04). CONCLUSION: Photocoagulation for clinically significant macular oedema with hard exudates, particularly when subfoveally located, was more often associated with subretinal fibrosis or atrophic creep of the pigment epithelium than photocoagulation of oedema without hard exudates. Hard exudates as well as complications after photocoagulation were more common in type 2 than in type 1 diabetes, resulting in poorer visual outcome in this group of patients.