Renal and vascular function in women with previous preeclampsia: A comparison of low- and high-degree proteinuria

The degree of proteinuria during preeclampsia has been considered to be a marker of severity of the disease and of endothelial dysfunction. The aim of the study was to assess whether the degree of proteinuria in preeclamptic pregnancy is related to impairment of vascular dilatation and/or kidney function years after the index pregnancy. Thirty women with a history of severe preeclampsia divided into low (n=8, dU-prot <5g/day) and high (n=22, dU-prot ≥5g/day) proteinuric groups and 21 women with previous normotensive pregnancy were studied 5–6 years after index pregnancy. Renal function and blood pressure were assessed together with venous occlusion plethysmography, where changes in brachial artery blood flow, induced by intra-arterial infusions of an endothelium-independent (sodium nitroprusside) and an endothelium-dependent (acetylcholine) vasodilator, were measured. The results showed similar renal function in all groups. There was no difference in vasodilation between preeclamptic groups and controls or correlation between degree of proteinuria during index pregnancy and present vasodilation. We conclude that the degree of proteinuria during preeclampsia does not predict vascular dilatation or renal function 5–6 years after preeclamptic pregnancy

The association between bacterial infections and the risk of coronary heart disease in type 1 diabetes

Background Diabetes increases the risk of infections as well as coronary heart disease (CHD). Whether infections increase the risk of CHD and how this applies to individuals with diabetes is unclear. Objectives To investigate the association between bacterial infections and the risk of CHD in type 1 diabetes. Methods Individuals with type 1 diabetes (n = 3781) were recruited from the Finnish Diabetic Nephropathy Study (FinnDiane), a prospective follow-up study. CHD was defined as incident events: fatal or non-fatal myocardial infarction, coronary artery bypass surgery or percutaneous coronary intervention, identified through national hospital discharge register data. Infections were identified through national register data on all antibiotic purchases from outpatient care. Register data were available from 1.1.1995-31.12.2015. Bacterial lipopolysaccharide (LPS) activity was measured from serum samples at baseline. Data on traditional risk factors for CHD were collected during baseline and consecutive visits. Results Individuals with an incident CHD event (n = 370) had a higher mean number of antibiotic purchases per follow-up year compared to those without incident CHD (1.34 [95% CI: 1.16-1.52], versus 0.79 [0.76-0.82],P <0.001), as well as higher levels of LPS activity (0.64 [0.60-0.67], versus 0.58 EU mL(-1)[0.57-0.59],P <0.001). In multivariable-adjusted Cox proportional hazards models, the mean number of antibiotic purchases per follow-up year was an independent risk factor for incident CHD (HR 1.21, 95% CI: 1.14-1.29,P <0.0001). High LPS activity was a risk factor for incident CHD (HR 1.93 [1.34-2.78],P <0.001) after adjusting for static confounders. Conclusion Bacterial infections are associated with an increased risk of incident CHD in individuals with type 1 diabetes.Peer reviewe

Waist‑height ratio and waist are the best estimators of visceral fat in type 1 diabetes

Visceral fat is associated with cardiovascular and kidney disease. However, the relationship between body composition and anthropometric measures in type 1 diabetes is unknown. Using z-statistics, we ranked the ability of body mass index (BMI), waist circumference (WC), waist-hip ratio (WHR), waist-height ratio (WHtR) and a body shape index (ABSI) to capture measures of body composition from 603 Dual-energy-X-Ray-Absorptiometry scans of adults with type 1 diabetes. Albuminuria was defined as urinary albumin excretion rate of at least 30 mg/24 h. Women with albuminuria had higher visceral fat mass % (VFM%) (0.9 vs. 0.5%, p = 0.0017) and lower appendicular lean mass % (AppLM%) (25.4 vs 26.4%, p = 0.03) than those without. Men with albuminuria had higher VFM% (1.5 vs. 1.0%, p = 0.0013) and lower AppLM% (30.0 vs 32.3, p < 0.0001) than those without. In men, WHtR estimated VFM% best (z-statistics = 21.1), followed by WC (z = 19.6), BMI (z = 15.1), WHR (z = 14.6) and ABSI (z = 10.1). In women, the ranking was WC (z = 28.9), WHtR (z = 27.3), BMI (z = 20.5), WHR (z = 12.7) and ABSI (z = 10.5). Overall, the ranking was independent of albuminuria. Adults with type 1 diabetes and albuminuria have greater VFM% and lower AppLM% than those without. WHtR and WC best estimate the VFM% in this population, independently of albuminuria and sex.Peer reviewe

Associations of dietary macronutrient and fibre intake with glycaemia in individuals with Type 1 diabetes

Aims To study the association between dietary intake and glycaemia in Type 1 diabetes. Methods Data on energy and nutrient intakes, and the mean and coefficient of variation of self-monitored blood glucose measurements were obtained from records completed by 1000 adults with Type 1 diabetes. Associations between these measures of glycaemia and dietary intake were investigated using generalized linear regression, with and without macronutrient substitution. Results In the first set of analyses, fibre intake was associated with lower mean self-monitored blood glucose values (beta = -0.428, 95% CI -0.624 to -0.231; PPeer reviewe

Urinary Proteomics Identifies Cathepsin D as a Biomarker of Rapid eGFR Decline in Type 1 Diabetes

Publisher Copyright: © 2022 by the American Diabetes Association.OBJECTIVE Understanding mechanisms underlying rapid estimated glomerular filtration rate (eGFR) decline is important to predict and treat kidney disease in type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS We performed a case-control study nested within four T1D cohorts to identify urinary proteins associated with rapid eGFR decline. Case and control subjects were categorized based on eGFR decline ≥3 and <1 mL/min/1.73 m2 /year, respectively. We used targeted liquid chromatography–tandem mass spectrome-try to measure 38 peptides from 20 proteins implicated in diabetic kidney dis-ease. Significant proteins were investigated in complementary human cohorts and in mouse proximal tubular epithelial cell cultures. RESULTS The cohort study included 1,270 participants followed a median 8 years. In the discovery set, only cathepsin D peptide and protein were significant on full adjustment for clinical and laboratory variables. In the validation set, associations of cathepsin D with eGFR decline were replicated in minimally adjusted models but lost significance with adjustment for albuminuria. In a meta-analysis with combination of discovery and validation sets, the odds ratio for the association of cathepsin D with rapid eGFR decline was 1.29 per SD (95% CI 1.07–1.55). In complementary human cohorts, urine cathepsin D was associated with tubulointerstitial injury and tubulointerstitial cathepsin D expression was associated with increased cortical interstitial fractional volume. In mouse proximal tubular epithelial cell cultures, advanced glycation end product–BSA increased cathepsin D activity and inflammatory and tubular injury markers, which were further increased with cathepsin D siRNA. CONCLUSIONS Urine cathepsin D is associated with rapid eGFR decline in T1D and reflects kidney tubulointerstitial injury.Peer reviewe

Efficacy of vildagliptin in combination with insulin in patients with type 2 diabetes and severe renal impairment

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Ammonia in breath and emitted from skin

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Association Analysis of Type 2 Diabetes Loci in Type 1 Diabetes

OBJECTIVE—To search for a possible association of type 1 diabetes with 10 validated type 2 diabetes loci, i.e., PPARG, KCNJ11, WFS1, HNF1B, IDE/HHEX, SLC30A8, CDKAL1, CDKN2A/B, IGF2BP2, and FTO/RPGRIP1L