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Aim: Angiotensin receptor blockers (ARBs) reduce vascular complications in diabetes independently of blood pressure. Experimental studies suggested that ARBs may restore the detoxifying enzyme glyoxalase 1, thereby lowering dicarbonyls such as methylglyoxal. Human data on the effects of ARBs on plasma dicarbonyl levels are lacking. We investigated, in individuals with type 2 diabetes, whether irbesartan lowered plasma levels of the dicarbonyls methylglyoxal, glyoxal, 3‐deoxyglucosone and their derived advanced glycation end products (AGEs), and increased d‐lactate, reflecting greater methylglyoxal flux. Methods: We analysed a subset of the Irbesartan in Patients with T2D and Microalbuminuria (IRMA2) study. We measured plasma dicarbonyls methylglyoxal, glyoxal and 3‐deoxyglucosone, free AGEs and d‐lactate using ultra‐performance liquid chromatography tandem mass‐spectrometry (UPLC‐MS/MS) in the treatment arm receiving 300 mg irbesartan (n = 121) and a placebo group (n = 101) at baseline and after 1 and 2 years. Effect of treatment was analysed with repeated measurements ANOVA. Results: There was a slight, but significant difference in baseline median methylglyoxal levels [placebo 1119 (907–1509) nmol/l vs. irbesartan 300 mg 1053 (820–1427) nmol/l], but no significant changes were observed in any of the plasma dicarbonyls over time in either group and there was no effect of irbesartan treatment on plasma free AGEs or d‐lactate levels at either 1 or 2 years. Conclusion: Irbesartan treatment does not change plasma levels of the dicarbonyls methylglyoxal, glyoxal and 3‐deoxyglucosone, free AGEs or d‐lactate in type 2 diabetes. This indicates that increased dicarbonyls in type 2 diabetes are not targetable by ARBs, and other approaches to lower systemic dicarbonyls are needed in type 2 diabetes. (Clinical Trial Registry No: #NCT00317915). [ABSTRACT FROM AUTHOR]

Background: Evidence links the lectin pathway of complement activation to diabetic kidney disease. Upon carbohydrate-recognition by pattern-recognition molecules, eg, mannan-binding lectin (MBL), the MBL-associated serine protease (MASP-2) is activated and initiates the complement cascade. The MASP2 gene encodes MASP-2 and the alternative splice product MBL-associated protein 19 (MAp19). Both MAp19 and MASP-2 circulate in complex with MBL. We tested the hypothesis that MAp19 and MASP-2 concentrations predict the risk of incident microalbuminuria.Methods: Baseline MAp19 and MASP-2 were measured in 270 persons with newly diagnosed type 1 diabetes tracked for incidence of persistent microalbuminuria in a prospective observational 18-year-follow-up study.Results: Seventy-five participants (28%) developed microalbuminuria during follow-up. MBL-associated protein 19 concentrations were higher in participants that later progressed to microalbuminuria as compared with those with persistent normoalbuminuria (268 ng/mL [95% CI, 243-293] vs 236 ng/mL [95% CI, 223-250], P = .02). Participants with MAp19 concentration within the highest quartile of the cohort had an increased risk of microalbuminuria as compared with participants with MAp19 concentration within the combined lower 3 quartiles in unadjusted Cox analysis, hazard ratio 1.86 ([95% CI, 1.17-2.96], P = .009). This remained significant in adjusted models, eg, adjusting for age, sex, HbA1c , systolic blood pressure, urinary albumin excretion, smoking, serum creatinine, and serum cholesterol. MBL-associated serine protease concentration was not associated with incidence of microalbuminuria.Conclusions: In conclusion, the results show an association between baseline MAp19 concentration and the incidence of microalbuminuria in an 18-year-follow-up study on persons with newly diagnosed type 1 diabetes. [ABSTRACT FROM AUTHOR]

Background: In addition to its glucose-lowering effect, metformin treatment has been suggested to improve lipidaemia in patients with type 2 diabetes. In contrast, in patients with type 1 diabetes (T1DM), information about the effect of metformin treatment on lipidaemia is limited. In this study, we report the effect of a 1-year treatment with metformin vs. placebo on plasma lipids in T1DM patients and persistent poor glycaemic control. Methods: One hundred T1DM patients with haemoglobinA1c (HbA1c) ≥8.5% during the year before enrolment entered a 1-month run-in period on placebo treatment. Thereafter, patients were randomized (baseline) to treatment with either metformin (1000 mg twice daily) or placebo for 12 months (double masked). Patients continued ongoing insulin therapy and their usual outpatient clinical care. Outcomes were assessed at baseline and after 1 year. Results: After 1 year, in those patients who did not start or stop statin therapy during the trial, metformin treatment significantly reduced total and LDL cholesterol by approximately 0.3 mmol/l compared with placebo (p = 0.021 and p = 0.018 respectively). Adjustment for statin use or known cardiovascular disease did not change conclusions. In statin users (metformin: n = 22, placebo: n = 13), metformin significantly lowered levels of LDL and non-HDL cholesterol by approximately 0.5 mmol/l compared with placebo (adjusted for changes in statin dose or agent: p = 0.048 and p = 0.033 respectively). HbA1c (previously reported) was not significant different between treatments. Conclusion: In patients with poorly controlled T1DM, at similar glycaemic levels, adjunct metformin therapy during 1 year significantly lowered levels of proatherogenic cholesterolaemia independent of statin therapy. [ABSTRACT FROM AUTHOR]

Objectives: Intrauterine growth retardation, as seen in individuals with low weight at birth, may give rise to a reduction in nephron number. Oligonephropathy has been linked to hypertension and renal disease in adult life. We tested the concept that low weight at birth acts as a risk factor for progression of diabetic nephropathy.Design and Subjects: We performed an observational follow-up study of 161 (97 men) type 1 diabetic patients with diabetic nephropathy [mean age (SD): 35 (11) years, mean duration of diabetes: 22 (8) years]. All patients had been followed for at least 3 years [median (range): 8 (3-20)] with at least three measurements [9 (3-31)] of glomerular filtration rate (GFR) (51Cr-EDTA). Information about birth size was obtained from midwife registrations.Settings: Steno Diabetes Center, a tertiary referral centre.Main Outcome Measures: Loss of kidney function according to birth weight and weight/length ratio at birth.Results: There was no correlation in univariate analysis between birth weight or weight/length ratio and rate of decline in GFR, neither in men nor in women. Furthermore, the 27 patients with birth weights below the 20th centile had a rate of decline in GFR [median (range)] similar to the 134 patients above: 2.6 (-4.7; 9.6) vs. 3.4 (-2.3; 19.3) mL min(-1) year(-1), respectively (NS). A multiple regression analysis revealed that albuminuria, arterial blood pressure, and haemoglobin A1C during follow-up showed a significant correlation with the decline in GFR [R2 (adjusted) = 0.34], whereas birth weight and birth weight/length ratio did not.Conclusions: Our study does not suggest that weight at birth is associated with progression of established diabetic nephropathy in type 1 diabetic patients, whilst several other potential modifiable risk factors were identified. [ABSTRACT FROM AUTHOR]

Aims: Among patients with type 2 diabetes and albuminuria, cardiorenal morbidity and mortality are high despite multifactorial treatment. Short-term reduction in albuminuria is considered suggestive of long-term renoprotective effects. We evaluated the renal effects of the glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide on top of multifactorial care, including renin-angiotensin-system (RAS)-inhibition., Materials and Methods: Randomized, double-blind, placebo-controlled, cross-over trial including patients with type 2 diabetes and persistent albuminuria (urinary albumin-to-creatinine ratio >30 mg/g) and estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m 2 . Patients received liraglutide (1.8 mg/d) and matched placebo for 12 weeks in a random order. The primary endpoint was change in 24-h urinary albumin excretion rate (UAER)., Results: A total of 32 patients were randomized and 27 completed the study. After placebo treatment, geometric mean (IQR) UAER was 199 (81-531) mg/24-h, mean (SD) measured GFR (mGFR) 75 (36) mL/min/1.73 m 2 , 24-h blood pressure 145/80 (15/8) mm Hg and HbA1c 61 (11) mmol/mol. Liraglutide reduced HbA1c by 8 (95% CI: 5; 11) mmol/mol (P < .001) and weight by 1.8 (95% CI: 0.2; 3.4) kg (P = .032) compared to placebo. Furthermore, liraglutide reduced UAER by 32 (95% CI: 7; 50)% ( P = .017) compared with placebo. The change in mGFR was -5 (95% CI: -11; 2) mL/min/1.73 m 2 ( P = .15), and change in 24-h systolic blood pressure was -5 (95% CI: -10; 0) mm Hg ( P = .07). In multivariate regression models, change in UAER was associated with change in 24-h systolic blood pressure ( P = .025) but not with change in HbA1c, weight or mGFR ( P ≥ .14), overall model R 2 = .39., Conclusions: Our placebo-controlled randomized trial suggests that liraglutide has renoprotective effects on top of multifactorial treatment, including RAS-inhibition, in patients with type 2 diabetes and albuminuria., (© 2016 John Wiley & Sons Ltd.)