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Aim: To compare nocturnal glucose profiles according to hourly plasma glucose measurements during treatment with insulin degludec and insulin glargine U100 in a cohort of people with type 1 diabetes prone to nocturnal severe hypoglycaemia. Materials and methods: The HypoDeg trial is a 2‐year investigator‐initiated, randomized, controlled crossover trial in 149 participants randomized to treatment with insulin degludec and insulin glargine U100 for 12 months each. The 51 participants in this predefined substudy stayed at least one night in hospital during each treatment arm for plasma glucose samples to be taken. Endpoints were glucose profiles, including mean plasma glucose, glycaemic variability and risk of hypoglycaemia. Results: There were no differences between treatments regarding mean plasma glucose. We saw a flatter glucose profile during insulin degludec compared with insulin glargine U100 treatment, which had a nadir at 4:00 AM, with a subsequent rise. During treatment with insulin degludec, the participants had lower glycaemic variability, with an estimated treatment difference of −4.3% (95% confidence interval [CI] −8.1 to −0.5; P < 0.05). Participants treated with insulin degludec were less likely to experience nocturnal hypoglycaemia below 3.0 mmol/L (hazard ratio 0.36 [95% CI 0.17‐0.73; P < 0.05]). Conclusion: Based on nocturnal plasma glucose measurements, treatment with insulin degludec compared with insulin glargine U100 administered in the evening results in lower glycaemic variability and lower risk of nocturnal hypoglycaemia without differences in mean plasma glucose. [ABSTRACT FROM AUTHOR]

Plasma exposure of the endothelin receptor antagonist atrasentan varies between individuals and is associated with nephroprotective effects and the risk of heart failure. We examined the influence of genetic polymorphisms on atrasentan plasma exposure and pharmacodynamic effects. We performed a substudy of the Study of Diabetic Nephropathy With Atrasentan (SONAR) trial which enrolled adults with type 2 diabetes and chronic kidney disease (estimated glomerular filtration rate: 25–75 mL/min/1.73 m2, and a urine albumin‐to‐creatinine ratio of 300–5,000 mg/g). Single nucleotide polymorphisms (SNPs) were determined for prespecified membrane transporters, metabolizing enzymes, and the endothelin‐1 peptide. The associations among genotype, atrasentan plasma exposure, and the effect of atrasentan on the prespecified kidney and heart failure hospitalization (HHF) outcomes was assessed with Cox proportional hazards regression models. Of 3,668 patients randomized, 2,329 (63.5%) consented to genotype analysis. Two SNPs in the SLCO1B1 gene (rs4149056 and rs2306283), encoding the hepatic organic anion transporter 1B1 (OATP1B1), showed the strongest association with atrasentan plasma exposure. Based on their SLCO1B1 genotype, patients were classified into normal (atrasentan area under the plasma‐concentration time curve from zero to infinity (AUC0−inf) 41.3 ng·h/mL) or slow (atrasentan AUC0−inf 49.7 ng·h/mL, P < 0.001) OATP1B1 transporter phenotypes. Among patients with a normal OATP1B1 phenotype, the hazard ratio (HR) with atrasentan for the primary kidney and HHF outcomes were 0.61 (95% confidence interval (CI): 0.45–0.81) and 1.35 (95% CI: 0.84–2.13), respectively. In the slow transporter phenotype, HRs for kidney and HHF outcomes were 1.95 (95% CI: 0.95–4.03, P‐interaction normal phenotype = 0.004), and 4.18 (95% CI: 1.37–12.7, P‐interaction normal phenotype = 0.060), respectively. OATP1B1 gene polymorphisms are associated with significant between‐patient variability in atrasentan plasma exposure and long‐term efficacy and safety. [ABSTRACT FROM AUTHOR]

Aim: To investigate whether the long‐acting insulin analogue insulin degludec compared with insulin glargine U100 reduces the risk of nocturnal symptomatic hypoglycaemia in patients with type 1 diabetes (T1D). Methods: Adults with T1D and at least one episode of nocturnal severe hypoglycaemia during the last 2 years were included in a 2‐year prospective, randomized, open, multicentre, crossover trial. A total of 149 patients were randomized 1:1 to basal‐bolus therapy with insulin degludec and insulin aspart or insulin glargine U100 and insulin aspart. Each treatment period lasted 1 year and consisted of 3 months of run‐in or crossover followed by 9 months of maintenance. The primary endpoint was the number of blindly adjudicated nocturnal symptomatic hypoglycaemic episodes. Secondary endpoints included the occurrence of severe hypoglycaemia. We analysed all endpoints by intention‐to‐treat. Results: Treatment with insulin degludec resulted in a 28% (95% CI: 9%‐43%; P =.02) relative rate reduction (RRR) of nocturnal symptomatic hypoglycaemia at level 1 (≤3.9 mmol/L), a 37% (95% CI: 16%‐53%; P =.002) RRR at level 2 (≤3.0 mmol/L), and a 35% (95% CI: 1%‐58%; P =.04) RRR in all‐day severe hypoglycaemia compared with insulin glargine U100. Conclusions: Patients with T1D prone to nocturnal severe hypoglycaemia have lower rates of nocturnal symptomatic hypoglycaemia and all‐day severe hypoglycaemia with insulin degludec compared with insulin glargine U100. [ABSTRACT FROM AUTHOR]

Atrasentan, an endothelin receptor antagonist, showed clinically significant albuminuria reduction with minimal signs of fluid retention in phase II trials. We evaluated whether plasma exposure was associated with long‐term outcomes for kidney protection and heart failure in the phase III SONAR trial (n = 3668) in type 2 diabetics with chronic kidney disease. A population pharmacokinetic model was used to estimate plasma exposure of atrasentan 0.75 mg/day. Parametric time‐to‐event models were used to quantify the association between plasma exposure and long‐term outcomes. Mean atrasentan plasma exposure was 41.4 ng.h/mL (2.5th to 97.5th P: 14.2 to 139.9). Compared with placebo, a mean atrasentan exposure translated in a hazard ratio of 0.76 (95% confidence interval (CI): 0.28–0.85) for kidney events and 1.13 (95% CI: 1.03–2.20) for heart failure events. At the mean atrasentan exposure, the kidney protective effect was larger than the increase in heart failure supporting the atrasentan 0.75 mg/day dose in this population. [ABSTRACT FROM AUTHOR]

Background: Clinical characteristics such as HbA1c, systolic blood pressure (SBP), albuminuria and estimated glomerular filtration rate (eGFR) are important when treating type 1 diabetes. We investigated the variability in these measures as risk markers for micro‐ and macrovascular complications. Methods: This prospective study included 1062 individuals with type 1 diabetes. Visit‐to‐visit variability of HbA1c, SBP, albuminuria and eGFR was calculated as the SD of the residuals in individual linear regression models using all available measures in a specified period of 3 years (VV). Endpoints included were as follows: cardiovascular events (CVE) defined as myocardial infarction, non‐fatal stroke, or coronary or peripheral arterial intervention; end‐stage kidney disease (ESKD) defined as eGFR <15 ml/min/1.73 m2, chronic dialysis or kidney transplantation; eGFR decline ≥30%; and mortality. Adjustment included age, sex, cholesterol, HbA1c, SBP, body mass index, smoking, albuminuria, eGFR, and mean, intercept, slope of respective exposure variables and regression models. Results: SBP VV was significantly associated with CVE (adjusted hazard ratio per 50% increase, (CI 95%); p: 1.21 [1.05–1.39]; p = 0.008), ESKD (1.51 [1.16–1.96]; p = 0.002) and mortality (1.25 [1.09–1.44]; p = 0.002). HbA1c VV was significantly associated with mortality (1.51 [1.30–1.75]; p < 0.001); albuminuria VV with eGFR decline (1.14 [1.08–1.20]; p = 0.024) and ESKD (1.14 [1.02–1.27]; p < 0.001), but neither CVE nor mortality. Adjusted eGFR VV was not associated with endpoints. Conclusion: In type 1 diabetes, higher variability of basic clinical risk markers adds important risk stratification information for the development of micro‐ and macrovascular complications. [ABSTRACT FROM AUTHOR]

Aim: To evaluate whether atrasentan plasma exposure explains between‐patient variability in urinary albumin‐to‐creatinine ratio (UACR) response, a surrogate for kidney protection, and B‐type natriuretic peptide (BNP) response, a surrogate for fluid expansion. Methods: Type 2 diabetic patients with chronic kidney disease (n = 4775) received 0.75 mg atrasentan for 6 weeks in the active run‐in period. Individual area under the concentration‐time‐curve (AUC) was estimated using a population pharmacokinetic model. The association between atrasentan AUC, other clinical characteristics, and UACR and BNP response, was estimated using linear regression. Results: The median atrasentan AUC was 43.8 ng.h/mL with a large variation among patients (2.5th‐97.5th percentiles [P]: 12.6 to 197.5 ng.h/mL). Median UACR change at the end of enrichment was −36.0% and median BNP change was 8.7%, which also varied among patients (UACR, 2.5th‐97.5th P: −76.2% to 44.5%; BNP, 2.5th‐97.5th P: −71.5% to 300.0%). In the multivariable analysis, higher atrasentan AUC was associated with greater UACR reduction (4.88% per doubling in ng.h/mL [95% confidence interval {CI}: 6.21% to 3.52%], P <.01) and greater BNP increase (3.08% per doubling in ng.h/mL [95% CI: 1.12% to 4.11%], P <.01) independent of estimated glomerular filtration rate, haemoglobin or BNP. Caucasian patients compared with black patients had greater UACR reduction (7.06% [95% CI: 1.38% to 13.07%]) and also greater BNP increase (8.75% [95% CI: 1.65% to 15.35%]). UACR response was not associated with BNP response (r = 0.06). Conclusion: Atrasentan plasma exposure varied among individual patients and partially explained between‐patient variability in efficacy and safety response. [ABSTRACT FROM AUTHOR]

Aims: Metformin could have benefits on cardiovascular disease and kidney disease progression but is often withheld from individuals with diabetes and chronic kidney disease (CKD) because of a concern that it may increase the risk of lactic acidosis. Materials and methods: All‐cause mortality, cardiovascular death, cardiovascular events (death, hospitalization for heart failure, myocardial infarction, stroke or myocardial ischemia), end stage renal disease (ESRD) and the kidney disease composite (ESRD or death) were compared in metformin users and non‐users with diabetes and CKD enrolled in the Trial to Reduce Cardiovascular Events with Aranesp (darbepoeitin‐alfa) Therapy (TREAT) (NCT00093015). Outcomes were compared after propensity matching of users and non‐users and in multivariable proportional hazards models. Results: There were 591 individuals who used metformin at baseline and 3447 non‐users. Among propensity‐matched users, the crude incidence rate for mortality, cardiovascular mortality, cardiovascular events and the combined endpoint was lower in metformin users than in non‐users, but ESRD was marginally higher (4.0% vs 3.6%). Metformin use was independently associated with a reduced risk of all‐cause mortality (HR, 0.49; 95% CI, 0.36‐0.69), cardiovascular death (HR, 0.49; 95% CI, 0.32‐0.74), the cardiovascular composite (HR, 0.67, 95% CI, 0.51‐0.88) and the kidney disease composite (HR, 0.77; 95% CI, 0.61‐0.98). Associations with ESRD (HR, 1.01; 95% CI, 0.65‐1.55) were not significant. Results were qualitatively similar in adjusted analyses of the full population. Two cases of lactic acidosis were observed. Conclusions: Metformin may be safer for use in CKD than previously considered and may lower the risk of death and cardiovascular events in individuals with stage 3 CKD. [ABSTRACT FROM AUTHOR]

Sodium retention and volume overload are the main determinants of poor response to renin‐angiotensin‐aldosterone system (RAAS) inhibition in patients with diabetes. As volume excess can exist without symptoms, biomarkers are needed to identify a priori which patients are volume overloaded and may experience less benefit from RAAS inhibition. N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) is released in the setting of increased cardiac wall stress and volume overload. We conducted a post hoc analysis among 5081 patients with type 2 diabetes mellitus participating in the ALTITUDE trial to investigate whether NTproBNP can predict the effects of additional therapy with aliskiren on cardio‐renal endpoints. Aliskiren compared to placebo reduced the risk of the primary cardio‐renal endpoint events by 20% (95% confidence interval [CI] 16 to 61) and 2% (95% CI –42 to 30) in the two lowest NT‐proBNP tertiles, and it increased the risk by 25% (95% CI –4 to 96) in the highest NT‐proBNP tertile (P value for trend = 0.009). Similar trends were observed for the cardiovascular and end‐stage renal disease endpoints. Effects of aliskiren compared to placebo on safety outcomes (hyperkalaemia and hospitalization for acute kidney injury) were independent of NT‐proBNP. In conclusion, baseline NT‐proBNP may be used as a marker to predict the response to aliskiren with regard to cardio‐renal outcomes when added to standard therapy with RAAS inhibition. [ABSTRACT FROM AUTHOR]

This study aimed to identify the optimal dose of the endothelin‐1 receptor antagonist atrasentan with maximal albuminuria reduction and minimal signs of sodium retention, as manifested by increase in bodyweight. Data from the RADAR‐JAPAN studies were used, evaluating the effect of 0.75 or 1.25 mg/d of atrasentan in 161 patients with type 2 diabetes and kidney disease. Individual pharmacokinetic parameters were estimated using a population pharmacokinetic approach. Subsequently, changes in the urinary albumin‐to‐creatinine ratio (UACR) and bodyweight from baseline after 2 weeks' exposure were modelled as a function of the pharmacokinetic parameters. The 0.75 and 1.25 mg doses showed a mean UACR reduction of 34.0% and 40.1%, whereas mean bodyweight increased by 0.9 and 1.1 kg, respectively. A large variation between individuals was observed in the UACR and bodyweight responses. Individual pharmacokinetic parameters correlated significantly with both individual UACR and bodyweight responses (P < .01). The individual response curves for UACR and bodyweight crossed at approximately the mean trough concentration of 0.75 mg atrasentan, indicating that 0.75 mg/d of atrasentan is the optimal dose for kidney protection with maximal efficacy (albuminuria reduction) and safety (minimal sodium retention). [ABSTRACT FROM AUTHOR]

Aim: The SONAR trial uses an enrichment design based on the individual response to the selective endothelin receptor antagonist atrasentan on efficacy (the degree of the individual response in the urinary albumin‐to‐creatinine ratio [UACR]) and safety/tolerability (signs of sodium retention and acute increases in serum creatinine) to assess the effects of this agent on major renal outcomes. The patient population and enrichment results are described here. Methods: Patients with type 2 diabetes with an estimated glomerular filtration rate (eGFR) within 25 to 75 mL/min/1.73 m2 and UACR between 300 and 5000 mg/g were enrolled. After a run‐in period, eligible patients received 0.75 mg/d of atrasentan for 6 weeks. A total of 2648 responder patients in whom UACR decreased by ≥30% compared to baseline were enrolled, as were 1020 non‐responders with a UACR decrease of <30%. Patients who experienced a weight gain of >3 kg and in whom brain natriuretic peptide exceeded ≥300 pg/mL, or who experienced an increase in serum creatinine >20% (0.5 mg/dL), were not randomized. Results: Baseline characteristics were similar for atrasentan responders and non‐responders. Upon entry to the study, median UACR was 802 mg/g in responders and 920 mg/g in non‐responders. After 6 weeks of treatment with atrasentan, the UACR change in responders was −48.8% (95% CI, −49.8% to −47.9%) and in non‐responders was −1.2% (95% CI, −6.4% to 3.9%). Changes in other renal risk markers were similar between responders and non‐responders except for a marginally greater reduction in systolic blood pressure and eGFR in responders. Conclusions: The enrichment period has successfully identified a population with a profound UACR reduction without clinical signs of sodium retention in whom a large atrasentan effect on clinically important renal outcomes is possible. The SONAR trial aims to establish whether atrasentan confers renal protection. [ABSTRACT FROM AUTHOR]

Aims: Individuals with diabetes and chronic kidney disease (CKD) are at high risk for renal events. Recent trials of novel treatments have been negative, possibly because of variability in response to treatment of the target risk factor. Atrasentan is a selective endothelin A receptor antagonist that reduces urinary albumin‐to‐creatinine ratio (UACR), with a large variability between patients. We are assessing its effect on renal outcomes in the Study Of diabetic Nephropathy with AtRasentan (SONAR; NCT01858532) with an enrichment design (>30% lowering of albuminuria) to select patients most likely to benefit. Materials and Methods: SONAR is a randomized, double‐blind, placebo‐controlled trial with approximately 3500 participants who have stage 2–4 CKD and macroalbuminuria and are receiving a maximum tolerated dose of a renin‐angiotensin system inhibitor. Results: After 6 weeks of exposure to atrasentan 0.75 mg once daily (enrichment period), participants with ≥30% UACR decrease and no tolerability issues (responders) were randomly assigned to placebo or atrasentan 0.75 mg/day. The responder group will be used for primary efficacy and safety analyses. Approximately 1000 participants with <30% UACR reduction (non‐responders) were also randomized to placebo or atrasentan. The primary endpoint is a composite of a sustained doubling of serum creatinine or end‐stage renal disease. The original power calculation indicated that a total of 425 primary renal events in the responder group provides 90% power to detect a 27% reduction in relative risk (alpha level of .05). Conclusion: SONAR aims to determine whether atrasentan added to guideline‐recommended therapies safely reduces the risk of CKD progression and delays the onset of end‐stage renal disease in patients with type 2 diabetes and nephropathy. SONAR also aims to establish whether the enrichment of patients based on their initial “surrogate” response to atrasentan will deliver a trial design in accord with personalized treatment of diabetic kidney disease. [ABSTRACT FROM AUTHOR]

We assessed the effect of atrasentan therapy on a pre-specified panel of 13 urinary metabolites known to reflect mitochondrial function in patients with diabetic kidney disease. This post-hoc analysis was performed using urine samples collected during the RADAR study which was a randomized, double-blind, placebo-controlled trial that tested the effects of atrasentan on albuminuria reduction in patients with type 2 diabetes and nephropathy. At baseline, 4 of the 13 metabolites, quantified by gas-chromatography mass spectrometry, were below detectable levels, and 6 were reduced in patients with eGFR < 60 mL/min/1.73 m2. After 12 weeks of atrasentan treatment in patients with eGFR < 60 mL/min/1.73 m2, a single-value index of the metabolites changed by −0.31 (95%CI −0.60 to −0.02; P = .035), −0.08 (−12 to 0.29; P = .43) and 0.01 (−0.21 to 0.19; P = .913) in placebo, atrasentan 0.75 and 1.25 mg/d, respectively. The metabolite index difference compared to placebo was 0.13 (−0.17 to 0.43; P = .40) and 0.35 (0.05-0.65; P = .02) for atrasentan 0.75 and 1.25 mg/d, respectively. These data corroborate previous findings of mitochondrial dysfunction in patients with type 2 diabetes, nephropathy and eGFR < 60 mL/min/1.73 m2, suggesting that atrasentan may prevent the progression of mitochondrial dysfunction common to this specific patient population. Future studies of longer treatment duration with atrasentan are indicated. [ABSTRACT FROM AUTHOR]

Aims The selective endothelin ( ET) A receptor antagonist atrasentan has been shown to lower albuminuria in North American and Asian patients with type 2 diabetes and nephropathy. As drug responses to many drugs may differ between North American and Asian populations, we assessed the influence of geographical region on the albuminuria and fluid retention response to atrasentan. Materials and methods Two 12-week double-blind randomised controlled trials were performed with atrasentan 0.75 or 1.25 mg/d vs placebo in patients with type 2 diabetes and nephropathy. The efficacy endpoint was the percentage change in albuminuria. Bodyweight change, a proxy of fluid retention, was used as a safety endpoint. Pharmacodynamics were determined in Asians ( N = 77) and North Americans ( N = 134). Atrasentan plasma concentration was measured in 161 atrasentan-treated patients. Results Mean albuminuria reduction in Asian, compared to North American, patients was, respectively, −34.4% vs −26.3% for 0.75 mg/d ( P = .44) and −48.0% vs −28.9% for 1.25 mg/d ( P = .035). Bodyweight gain did not differ between North American and Asian populations. Atrasentan plasma concentrations were higher in Asians compared to North Americans and correlated with albuminuria response (7.2% albuminuria reduction per doubling atrasentan concentration; P = .024). Body surface area (β = −1.09 per m2; P < .001) and bilirubin, as a marker of hepatic organic anion transporter activity, (β = 0.69 per mg/ dL increment; P = .010) were independent determinants of atrasentan plasma concentration; correction by body surface area and bilirubin left no significant difference in plasma concentration between Asian and North American populations. Conclusion The higher exposure and albuminuria reduction of atrasentan in Asian patients is not associated with more fluid retention, suggesting that Asian patients are less sensitive to atrasentan-induced sodium retention. [ABSTRACT FROM AUTHOR]

Aims Angiotensin receptor blockers (ARBs) are renoprotective and targeted to blood pressure. However, ARBs have multiple other (off-target) effects which may affect renal outcome. It is unknown whether on-target and off-target effects are congruent within individuals. If not, this variation in short term effects may have important implications for the prediction of individual long term renal outcomes. Our aim was to assess intra-individual variability in multiple parameters in response to ARBs in type 2 diabetes. Methods Changes in systolic blood pressure (SBP), albuminuria, potassium, haemoglobin, cholesterol and uric acid after 6 months of losartan treatment were assessed in the RENAAL database. Improvement in predictive performance of renal outcomes (ESRD or doubling serum creatinine) for each individual using ARB-induced changes in all risk markers was assessed by the relative integrative discrimination index (RIDI). Results SBP response showed high variability (mean -5.7 mmHg, 5th to 95th percentile -36.5 to +24.0 mmHg) between individuals. Changes in off-target parameters also showed high variability between individuals. No congruency was observed between responses to losartan in multiple parameters within individuals. Using individual responses in all risk markers significantly improved renal risk prediction (RIDI 30.4%, P < 0.01) compared with using only SBP changes. Results were successfully replicated in two independent trials with irbesartan, IDNT and IRMA-2. Conclusions In this post hoc analysis we showed that ARBs have multiple off-target effects which vary between and within individuals. Combining all ARB-induced responses beyond SBP provides a more accurate prediction of who will benefit from ARB therapy. Prospective trials are required to validate these findings. [ABSTRACT FROM AUTHOR]

For approximately 6 years, the only commercially available direct renin inhibitor, aliskiren, which inhibits the renin-angiotensin-aldosterone system at the initial rate limiting step, has been marketed for the treatment of hypertension. Concurrently, much attention has been given to the possibility that renin inhibition could hold potential for improved treatment in patients with chronic kidney disease, with diabetic nephropathy as an obvious group of patients to investigate, as the activity of the renin-angiotensin-aldosterone system is enhanced in these patients and as there is an unmet need for improved treatment and prognosis in these patients. Several short term studies have been performed in diabetic nephropathy, showing a consistent effect on the surrogate endpoint lowering of albuminuria, both as monotherapy and in combination with other blockers of the renin-angiotensin-aldosterone system. In addition, combination treatment also seemed safe and effective in patients with impaired kidney function. These initial findings formed the basis for the design of a large morbidity and mortality trial investigating aliskiren as add-on to standard treatment. The study has just concluded, but was terminated early as a beneficial effect was unlikely and there was an increased frequency of side effects. Also in non-diabetic kidney disease a few intervention studies have been carried out, but there is no ongoing hard outcome study. In this review we provide the current evidence for renin inhibition in chronic kidney disease by reporting the studies published so far as well as a perspective on the future possibilites. [ABSTRACT FROM AUTHOR]

Objective Microalbuminuria and obesity are both associated with cardiovascular disease (CVD). The aim of this study was to determine the association between obesity (measured by body mass index, waist-to-hip ratio, waist circumference) and different levels of microalbuminuria. We also aimed to determine the risk of death and CVD at different levels of microalbuminuria and obesity. Design Population-based observational study based on 2696 men and women, 30–70 years of age. Urinary albumin excretion (UAE), body mass index, waist-to-hip ratio, waist circumference and other cardiovascular risk factors were measured during the years 1992–1994 at the Copenhagen City Heart Study. End-points were registered until 1999–2000 with respect to CVD and until 2004 with respect to death. Results There was a strong association between microalbuminuria and obesity. Microalbuminuria and obesity had additive effects on the relative risk of death independently of other risk factors. In contrast there was no statistically significant association between microalbuminuria and risk of CVD when stratified by obesity. Conclusions Microalbuminuria (UAE > 5 µg/min) confers increased risk of death and to a similar extent as obesity. This effect is independent of concomitant obesity. We suggest microalbuminuria to be included in health examinations besides measurements of obesity. [ABSTRACT FROM AUTHOR]

ABSTRACT. Purpose: This study presents an evaluation of cataract surgery on diabetic patients. One experienced surgeon carried out phaco emulsification on all subjects and the same surface-coated one-piece PMMA-lens-type was implanted. The lens fluorescence and the blood-aqueous barrier (BAB) were then evaluated as experimental preoperative risk indicators. Results: During follow-up, 10 out of 39 diabetic patients progressed unilaterally in diabetic retinopathy or developed macular oedema, a significant relative risk. Neither lens fluorescence, BAB, HbA1c , level of retinopathy, type/duration of diabetes, diabetes treatment or antihypertensive treatment differed significantly between the group of patients with postoperative progression of retinopathy/macular oedema and those without. Results indicated NIDDM (non-insulin-dependent diabetes mellitus/type 2 diabetes) patients might have increased risk of a postoperative macular oedema. Conclusion: When diabetic retinopathy (DR) is not in a proliferative phase it should not be regarded as a contraindication to modern cataract surgery. Neither lens fluorescence nor BAB is valuable as a risk indicator for postoperative progression of DR. [ABSTRACT FROM AUTHOR]