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1.
Diabetes Obes Metab ; 2020 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-32618386

RESUMO

AIMS: It is important to understand links among urinary albumin-to-creatinine ratio (UACR), estimated glomerular filtration rate (eGFR) and outcomes in contemporary type 2 diabetes (T2D) populations receiving standard treatments. We aimed to assess cardiorenal outcomes by baseline UACR and eGFR in the contemporary LEADER cohort. MATERIALS AND METHODS: LEADER was a multinational, double-blind trial. Patients with T2D and high cardiovascular (CV) risk were randomized 1:1 to the glucagon-like peptide-1 analog liraglutide (≤1.8 mg daily; n = 4668) or placebo (n = 4672) plus standard care and followed for 3.5 to 5 years. Primary composite outcome: time to first non-fatal myocardial infarction, non-fatal stroke or CV death. Post hoc Cox regression analyses of outcomes by baseline UACR and eGFR subgroups were conducted with adjustment for baseline variables. RESULTS: In the LEADER population 1598 (17.5%), 2917 (31.9%), 1200 (13.1%), 1611 (17.6%), 845 (9.2%) and 966 (10.6%) had UACR =0, >0-<15, 15-<30, 30-<100, 100-<300, ≥300 mg/g respectively. Increasing UACR and decreasing eGFR were linked with higher risks of the primary outcome, heart failure hospitalization, a composite renal outcome and death (P-values for Cochran-Armitage test for trends all <0.0001). Across UACR and eGFR subgroups, risks of cardiorenal events and death were generally lower or similar with liraglutide versus placebo. CONCLUSIONS: In a contemporary T2D population, increasing baseline UACR and declining eGFR were linked with higher risks of cardiorenal events and death. ClinicalTrials.gov NCT01179048. This article is protected by copyright. All rights reserved.

2.
N Engl J Med ; 382(26): 2493-2503, 2020 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-32579810

RESUMO

BACKGROUND: Higher serum urate levels are associated with an increased risk of diabetic kidney disease. Lowering of the serum urate level with allopurinol may slow the decrease in the glomerular filtration rate (GFR) in persons with type 1 diabetes and early-to-moderate diabetic kidney disease. METHODS: In a double-blind trial, we randomly assigned participants with type 1 diabetes, a serum urate level of at least 4.5 mg per deciliter, an estimated GFR of 40.0 to 99.9 ml per minute per 1.73 m2 of body-surface area, and evidence of diabetic kidney disease to receive allopurinol or placebo. The primary outcome was the baseline-adjusted GFR, as measured with iohexol, after 3 years plus a 2-month washout period. Secondary outcomes included the decrease in the iohexol-based GFR per year and the urinary albumin excretion rate after washout. Safety was also assessed. RESULTS: A total of 267 patients were assigned to receive allopurinol and 263 to receive placebo. The mean age was 51.1 years, the mean duration of diabetes 34.6 years, and the mean glycated hemoglobin level 8.2%. The mean baseline iohexol-based GFR was 68.7 ml per minute per 1.73 m2 in the allopurinol group and 67.3 ml per minute per 1.73 m2 in the placebo group. During the intervention period, the mean serum urate level decreased from 6.1 to 3.9 mg per deciliter with allopurinol and remained at 6.1 mg per deciliter with placebo. After washout, the between-group difference in the mean iohexol-based GFR was 0.001 ml per minute per 1.73 m2 (95% confidence interval [CI], -1.9 to 1.9; P = 0.99). The mean decrease in the iohexol-based GFR was -3.0 ml per minute per 1.73 m2 per year with allopurinol and -2.5 ml per minute per 1.73 m2 per year with placebo (between-group difference, -0.6 ml per minute per 1.73 m2 per year; 95% CI, -1.5 to 0.4). The mean urinary albumin excretion rate after washout was 40% (95% CI, 0 to 80) higher with allopurinol than with placebo. The frequency of serious adverse events was similar in the two groups. CONCLUSIONS: We found no evidence of clinically meaningful benefits of serum urate reduction with allopurinol on kidney outcomes among patients with type 1 diabetes and early-to-moderate diabetic kidney disease. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; PERL ClinicalTrials.gov number, NCT02017171.).

4.
J Nephrol ; 2020 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-32474762

RESUMO

The use of "omics" is increasing in research areas looking to identify biomarkers or early preclinical signs of disease or to increase understanding of complex pathological processes that determines prognosis of the disease. Diabetic kidney disease is no exception as it is an area in need of further improvement of both understanding and prognosis. In addition, there is a notion that pretreatment investigations using techniques like proteomics, lipidomics and metabolomics can help individualize therapy thus fulfilling the wish for personalized medicine. An increasing number of cohort studies using these techniques are published, but only few have been validated in external cohorts or even replicated by other groups. In essence, to achieve clinical impact and usefulness, prospective validation is needed. So far, only the urinary proteomics based PRIORITY study has tried to do this, as discussed in this review. Other areas are promising, but are currently lacking such efforts. In this review we report and discuss the current status of urinary proteomics as well as plasma metabolomics and lipidomics with an overview of the results so far, and with some comments and perspectives regarding future developments and implementation. As is evident, these techniques are promising, but there is still some way before widespread clinical use can be foreseen.

7.
Eur J Epidemiol ; 2020 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-32383070

RESUMO

Epidemiology studies suggested that low birthweight was associated with a higher risk of hypertension in later life. However, little is known about the causality of such associations. In our study, we evaluated the causal association of low birthweight with adulthood hypertension following a standard analytic protocol using the study-level data of 183,433 participants from 60 studies (CHARGE-BIG consortium), as well as that with blood pressure using publicly available summary-level genome-wide association data from EGG consortium of 153,781 participants, ICBP consortium and UK Biobank cohort together of 757,601 participants. We used seven SNPs as the instrumental variable in the study-level analysis and 47 SNPs in the summary-level analysis. In the study-level analyses, decreased birthweight was associated with a higher risk of hypertension in adults (the odds ratio per 1 standard deviation (SD) lower birthweight, 1.22; 95% CI 1.16 to 1.28), while no association was found between genetically instrumented birthweight and hypertension risk (instrumental odds ratio for causal effect per 1 SD lower birthweight, 0.97; 95% CI 0.68 to 1.41). Such results were consistent with that from the summary-level analyses, where the genetically determined low birthweight was not associated with blood pressure measurements either. One SD lower genetically determined birthweight was not associated with systolic blood pressure (ß = - 0.76, 95% CI - 2.45 to 1.08 mmHg), 0.06 mmHg lower diastolic blood pressure (ß = - 0.06, 95% CI - 0.93 to 0.87 mmHg), or pulse pressure (ß = - 0.65, 95% CI - 1.38 to 0.69 mmHg, all p > 0.05). Our findings suggest that the inverse association of birthweight with hypertension risk from observational studies was not supported by large Mendelian randomization analyses.

8.
J Diabetes Complications ; 34(7): 107593, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32349898

RESUMO

AIMS: Lipoprotein(a)(Lp(a)) has emerged as an independent risk marker for cardiovascular disease (CVD) in the general population and among persons with existing CVD. We investigated associations between serum Lp(a)concentrations and renal function decline, incident CVD and all-cause mortality in individuals with type 2 diabetes (T2D) and microalbuminuria. METHODS: Prospective study including 198 individuals with T2D, microalbuminuria and no CVD. Yearly p-creatinine was measured after baseline in 176 of the participants. The renal endpoint was defined as decline in eGFR of >30% from baseline. CVD events and mortality were tracked from national registries. Cox regression analyses were applied both unadjusted and adjusted for traditional risk factors (sex, age, systolic blood pressure, LDL-cholesterol, smoking, HbA1c, creatinine and urinary albumin creatinine ratio (UAER)). RESULTS: Baseline mean (SD) age was 59 (9)years, eGFR 89 (17) mL/min/1.73 m2, 77% were male, and median [IQR] UAER was 103 [38-242] mg/24-h. Median Lp(a)was 8.04 [3.42-32.3] mg/dL. Median follow-up was 6.1 years; 38 CVD events, 26 deaths and 43 renal events were recorded. For each doubling of baseline Lp(a), the following hazard ratios (95% confidence intervals) were found before and after adjustment respectively: 0.98 (0.84-1.15) and 1.01 (0.87-1.18) for decline in eGFR > 30%, 0.96 (0.81-1.13) and 0.99 (0.82-1.18) for CVD events, 1.04 (0.85-1.27) and 1.06 (0.87-1.30) for all-cause mortality. CONCLUSIONS: In this cohort of individuals with T2D and microalbuminuria, the baseline concentration of Lp(a)was not a risk marker for renal function decline, CVD events or all-cause mortality.

9.
J Diabetes Complications ; 34(7): 107590, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32340841

RESUMO

AIMS: Sodium glucose transport inhibitors (SGLT2i) can reduce risk of heart failure (HF) and cardiovascular death in people with type 2 diabetes (T2D) and existing cardiovascular disease. Our aim was to examine the effect of the SGLT2i dapagliflozin on cardiac function in people with T2D and albuminuria. METHODS: A secondary analysis of a double-blind, randomized, cross-over study of 12 weeks treatment with dapagliflozin 10 mg versus placebo. Myocardial function was assessed by echocardiography and biomarkers of cardiac risk were measured. An exploratory diastolic composite of echocardiographic variables was computed. RESULTS: Of the 36 participants completing the study 89% were male, mean age 64 ±â€¯8 years, diabetes duration 16.4 ±â€¯4.7 years and HbA1c 73 ±â€¯15 mmol/mol (8.9 ±â€¯1.4%), 30.6% had former cardiovascular events and 32% had macroalbuminuria. Mean left ventricular ejection fraction (LVEF) was 55.4% after placebo and 54.3% after dapagliflozin (p = 0.15), global longitudinal strain -16.1 vs. -15.9, (p = 0.64), E/e' 7.6 vs. 7.6 (p = 0.082), and tissue Doppler velocity e' 10.0 vs. 10.6 (p = 0.05). The composite score showed diastolic function improvement of 19.8% (p = 0.021). No other significant changes were observed. CONCLUSIONS: Dapagliflozin may have minor effects on diastolic function in people with T2D, albuminuria and preserved LVEF.

10.
J Clin Endocrinol Metab ; 105(7)2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32271379

RESUMO

CONTEXT: There is a need for novel biomarkers and better understanding of the pathophysiology of diabetic kidney disease. OBJECTIVE: To investigate associations between plasma metabolites and kidney function in people with type 2 diabetes (T2D). DESIGN: 3089 samples from individuals with T2D, collected between 1999 and 2015, from 5 independent Dutch cohort studies were included. Up to 7 years follow-up was available in 1100 individuals from 2 of the cohorts. MAIN OUTCOME MEASURES: Plasma metabolites (n = 149) were measured by nuclear magnetic resonance spectroscopy. Associations between metabolites and estimated glomerular filtration rate (eGFR), urinary albumin-to-creatinine ratio (UACR), and eGFR slopes were investigated in each study followed by random effect meta-analysis. Adjustments included traditional cardiovascular risk factors and correction for multiple testing. RESULTS: In total, 125 metabolites were significantly associated (PFDR = 1.5×10-32 - 0.046; ß = -11.98-2.17) with eGFR. Inverse associations with eGFR were demonstrated for branched-chain and aromatic amino acids (AAAs), glycoprotein acetyls, triglycerides (TGs), lipids in very low-density lipoproteins (VLDL) subclasses, and fatty acids (PFDR < 0.03). We observed positive associations with cholesterol and phospholipids in high-density lipoproteins (HDL) and apolipoprotein A1 (PFDR < 0.05). Albeit some metabolites were associated with UACR levels (P < 0.05), significance was lost after correction for multiple testing. Tyrosine and HDL-related metabolites were positively associated with eGFR slopes before adjustment for multiple testing (PTyr = 0.003; PHDLrelated < 0.05), but not after. CONCLUSIONS: This study identified metabolites associated with impaired kidney function in T2D, implying involvement of lipid and amino acid metabolism in the pathogenesis. Whether these processes precede or are consequences of renal impairment needs further investigation.

11.
Lancet Diabetes Endocrinol ; 8(4): 301-312, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32135136

RESUMO

BACKGROUND: Microalbuminuria is an early sign of kidney disease in people with diabetes and indicates increased risk of cardiovascular disease. We tested whether a urinary proteomic risk classifier (CKD273) score was associated with development of microalbuminuria and whether progression to microalbuminuria could be prevented with the mineralocorticoid receptor antagonist spironolactone. METHODS: In this multicentre, prospective, observational study with embedded randomised controlled trial (PRIORITY), we recruited people with type 2 diabetes, normal urinary albumin excretion, and preserved renal function from 15 specialist centres in ten European countries. All participants (observational cohort) were tested with the CKD273 classifier and classified as high risk (CKD273 classifier score >0·154) or low risk (≤0·154). Participants who were classified as high risk were entered into a randomised controlled trial and randomly assigned (1:1), by use of an interactive web-response system, to receive spironolactone 25 mg once daily or matched placebo (trial cohort). The primary endpoint was development of confirmed microalbuminuria in all individuals with available data (observational cohort). Secondary endpoints included reduction in incidence of microalbuminuria with spironolactone (trial cohort, intention-to-treat population) and association between CKD273 risk score and measures of impaired renal function based on estimated glomerular filtration rate (eGFR; observational cohort). Adverse events (particularly gynaecomastia and hyperkalaemia) and serious adverse events were recorded for the intention-to-treat population (trial cohort). This study is registered with the EU Clinical Trials Register (EudraCT 20120-004523-4) and ClinicalTrials.gov (NCT02040441) and is completed. FINDINGS: Between March 25, 2014, and Sept 30, 2018, we enrolled and followed-up 1775 participants (observational cohort), 1559 (88%) of 1775 participants had a low-risk urinary proteomic pattern and 216 (12%) had a high-risk pattern, of whom 209 were included in the trial cohort and assigned to spironolactone (n=102) or placebo (n=107). The overall median follow-up time was 2·51 years (IQR 2·0-3·0). Progression to microalbuminuria was seen in 61 (28%) of 216 high-risk participants and 139 (9%) of 1559 low-risk participants (hazard ratio [HR] 2·48, 95% CI 1·80-3·42; p<0·0001, after adjustment for baseline variables of age, sex, HbA1c, systolic blood pressure, retinopathy, urine albumin-to-creatinine ratio [UACR], and eGFR). Development of impaired renal function (eGFR <60 mL/min per 1·73 m2) was seen in 48 (26%) of 184 high-risk participants and 119 (8%) of 1423 low-risk participants (HR 3·50; 95% CI 2·50-4·90, after adjustment for baseline variables). A 30% decrease in eGFR from baseline (post-hoc endpoint) was seen in 42 (19%) of 216 high-risk participants and 62 (4%) of 1559 low-risk participants (HR 5·15, 95% CI 3·41-7·76; p<0·0001, after adjustment for basline eGFR and UACR). In the intention-to-treat trial cohort, development of microalbuminuria was seen in 35 (33%) of 107 in the placebo group and 26 (25%) of 102 in the spironolactone group (HR 0·81, 95% CI 0·49-1·34; p=0·41). In the safety analysis (intention-to-treat trial cohort), events of plasma potassium concentrations of more than 5·5 mmol/L were seen in 13 (13%) of 102 participants in the spironolactone group and four (4%) of 107 participants in the placebo group, and gynaecomastia was seen in three (3%) participants in the spironolactone group and none in the placebo group. One patient died in the placebo group due to a cardiac event (considered possibly related to study drug) and one patient died in the spironolactone group due to cancer, deemed unrelated to study drug. INTERPRETATION: In people with type 2 diabetes and normoalbuminuria, a high-risk score from the urinary proteomic classifier CKD273 was associated with an increased risk of progression to microalbuminuria over a median of 2·5 years, independent of clinical characteristics. However, spironolactone did not prevent progression to microalbuminuria in high-risk patients. FUNDING: European Union Seventh Framework Programme.

12.
Eur J Endocrinol ; 182(5): 481-488, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32209724

RESUMO

Aims: Patients with type 1 diabetes have a high risk of cardiovascular disease. Yet, the importance of routine assessment of myocardial function in patients with type 1 diabetes is not known. Thus, we examined the prognostic importance of NT-proBNP and E/e', an echocardiographic measure of diastolic function, in type 1 diabetes patients with preserved left ventricular ejection fraction (LVEF) and without known heart disease. Methods and results: Type 1 diabetes patients without known heart disease and LVEF ≥45% enrolled in the Thousand and 1 study were included and followed through nationwide registries. The risk of major cardiovascular events (MACE) and death associated with levels of NT-proBNP and E/e' was examined. Of 960 patients, median follow-up of 6.3 years (Q1-Q3: 5.7-7.0), 121 (12%) experienced MACE and 51 (5%) died. Increased levels of both NT-proBNP and E/e' were associated with worse outcomes (adjusted hazard ratios for MACE = 1.56 (1.23-1.98) and 4.29 (2.25-8.16) per Loge increase for NT-proBNP and E/e', respectively). NT-proBNP and E/e' combined significantly improved the discrimination power of the Steno T1D risk engine (MACE, C-index: 0.813 (0.779-0.847) vs 0.779 (0.742-0.816); P = 0.0001; All-cause mortality, C-index 0.855 (0.806-0.903) vs 0.828 (0.776-0.880); P = 0.03). Conclusion: In patients with type 1 diabetes, preserved ejection fraction, and no known heart disease, NT-proBNP and E/e' were associated with increased risk of MACE and all-cause mortality. The risks associated with NT-proBNP and E/e' combined identified patients at remarkably high risk.


Assuntos
Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/diagnóstico por imagem , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/diagnóstico por imagem , Ecocardiografia/métodos , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Adulto , Idoso , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Prognóstico , Volume Sistólico/fisiologia , Função Ventricular Esquerda/fisiologia
13.
Diabetes Obes Metab ; 22(6): 904-915, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32009286

RESUMO

The guidance issued to the pharmaceutical industry by the US Food and Drug Administration in 2008 has led to the publication of a series of randomized, controlled cardiovascular outcomes trials with newer therapeutic classes of glucose-lowering medications. Several of these trials, which evaluated the newer therapeutic classes of sodium-glucose co-transporter-2 inhibitors and glucagon-like peptide-1 receptor agonists, have reported a reduced incidence of major adverse cardiovascular and/or renal outcomes, usually relative to placebo and standard of care. Metformin was the first glucose-lowering agent reported to improve cardiovascular outcomes in the UK Prospective Diabetes Study (UKPDS) and thus became the foundation of standard care. However, as this clinical trial reported more than 20 years ago, differences from current standards of trial design and evaluation complicate comparison of the cardiovascular profiles of older and newer agents. Our article revisits the evidence for cardiovascular protection with metformin and reviews its effects on the kidney.

15.
Nephrol Dial Transplant ; 35(2): 274-282, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-32030417

RESUMO

BACKGROUND: Recent cardiovascular outcome trials have shown that sodium-glucose co-transporter 2 (SGLT2) inhibitors slow the progression of chronic kidney disease (CKD) in patients with type 2 diabetes at high cardiovascular risk. Whether these benefits extend to CKD patients without type 2 diabetes or cardiovascular disease is unknown. The Dapagliflozin and Prevention of Adverse Outcomes in CKD (DAPA-CKD) trial (NCT03036150) will assess the effect of the SGLT2 inhibitor dapagliflozin on renal and cardiovascular events in a broad range of patients with CKD with and without diabetes. METHODS: DAPA-CKD is a randomized, double-blind, placebo-controlled, trial in which ∼4300 patients with CKD Stages 2-4 and elevated urinary albumin excretion will be enrolled. The vast majority will be receiving a maximum tolerated dose of a renin-angiotensin system inhibitor at enrolment. RESULTS: After a screening assessment, eligible patients with a urinary albumin:creatinine ratio ≥200 mg/g and estimated glomerular filtration rate (eGFR) between 25 and 75 mL/min/1.73 m2 are randomly assigned to placebo or dapagliflozin 10 mg/day. Enrolment is monitored to ensure that at least 30% of patients do not have diabetes and that no more than 10% have an eGFR >60 mL/min/1.73 m2. The primary endpoint is a composite of a sustained decline in eGFR of ≥50%, end-stage renal disease, renal death or cardiovascular death. The trial will conclude when 681 primary renal events have occurred, providing 90% power to detect a 22% relative risk reduction (α level of 0.05). CONCLUSION: DAPA-CKD will determine whether the SGLT2 inhibitor dapagliflozin, added to guideline-recommended therapies, safely reduces the rate of renal and cardiovascular events in patients across multiple CKD stages with and without diabetes.

16.
Cardiovasc Res ; 2020 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-32077919

RESUMO

AIMS: Diabetes is a known risk factor for coronary artery disease. There is accumulating evidence that coronary artery disease pathogenesis differs for individuals with type 1 diabetes. However, the genetic background has not been extensively studied. We aimed to discover genetic loci increasing coronary artery disease susceptibility especially in type 1 diabetes, to examine the function of these discoveries and to study the role of the known risk loci in type 1 diabetes. METHODS AND RESULTS: We performed the largest genome-wide association study to date for coronary artery disease in type 1 diabetes, comprising 4869 individuals with type 1 diabetes (cases/controls: 941/3928). Two loci reached genome-wide significance, rs1970112 in CDKN2B-AS1 (OR = 1.32, p=1.50 × 10-8), and rs6055069 on DEFB127 promoter (OR = 4.17, p=2.35 × 10-9), with consistent results in survival analysis. The CDKN2B-AS1 variant replicated (p=0.04) when adjusted for diabetic kidney disease in three additional type 1 diabetes cohorts (cases/controls: 434/3123). Furthermore, we explored the function of the lead discoveries with a cardio-phenome-wide analysis. Among the eight suggestive loci (p<1 × 10-6), rs70962766 near B3GNT2 associated with central blood pressure, rs1344228 near CNTNAP5 with intima media thickness, and rs2112481 on GRAMD2B promoter with serum leucocyte concentration. Finally, we calculated genetic risk scores for individuals with type 1 diabetes with the known susceptibility loci. General population risk variants were modestly but significantly associated with coronary artery disease also in type 1 diabetes (p=4.21 × 10-7). CONCLUSIONS: While general population coronary artery disease risk loci had limited effect on the risk in type 1 diabetes, for the first time, variants at the CDKN2B-AS1 locus were robustly associated with coronary artery disease in individuals with type 1 diabetes. The novel finding on ß-defensin DEFB127 promoter provides a link between diabetes, infection susceptibility and coronary artery disease, although pending on future confirmation. TRANSLATIONAL PERSPECTIVE: Genetic association studies enable the discovery of novel genes and genetic pathways associated with the disease. Thus, this study provides an insight into coronary artery disease mechanisms specific to type 1 diabetes. The DEFB127 discovery may lead to a therapeutic target and improve patient care, if replicated in the future. Furthermore, genetic studies on coronary artery disease in type 1 diabetes are required for accurate personalized treatment plans achieved through genetic data for those with type 1 diabetes.

17.
Cardiovasc Diabetol ; 19(1): 16, 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-32041610

RESUMO

BACKGROUND: Cardiac adipose tissue may have local paracrine effects on epicardial arteries and the underlying myocardium, promoting calcification and affecting myocardial microcirculation. We explored whether the total amount of cardiac adipose tissue was associated with coronary artery calcium score (CAC) and myocardial flow reserve in persons with type 1 or type 2 diabetes and healthy controls. METHODS: We studied three groups: (1) 30 controls, (2) 60 persons with type 1 diabetes and (3) 60 persons with type 2 diabetes. The three groups were matched for sex and age. The three groups derived from retrospective analysis of two clinical studies. All underwent cardiac 82Rb positron emission tomography/computed tomography (PET/CT) scanning. Cardiac adipose tissue volume (the sum of epicardial and pericardial fat), CAC, and myocardial flow reserve (ratio of pharmacological stress flow and rest flow) were evaluated using semiautomatic software. We applied linear regression to assess the association between cardiac adipose tissue, CAC and myocardial flow reserve. RESULTS: Mean (SD) cardiac adipose tissue volume was 99 (61) mL in the control group, 106 (78) mL in the type 1 diabetes group and 228 (97) mL in the type 2 diabetes group. Cardiac adipose tissue was positively associated with body mass index in all three groups (p ≤ 0.02). In the controls, cardiac adipose tissue was positively associated with CAC score (p = 0.008) and negatively associated with myocardial flow reserve (p = 0.005). However, cardiac adipose tissue was not associated with CAC or myocardial flow reserve in the groups including persons with type 1 or type 2 diabetes (p ≥ 0.50). CONCLUSIONS: In contrast to what was found in healthy controls, we could not establish a relation between cardiac adipose tissue and coronary calcification or myocardial microvascular function in person with type 1 or type 2 diabetes. The role of cardiac adipose tissue in cardiovascular disease in diabetes remains unclear.

18.
Sci Rep ; 10(1): 885, 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31965056

RESUMO

The chemical composition of feces plays an important role in human metabolism. Metabolomics and lipidomics are valuable tools for screening the metabolite composition in feces. Here we set out to describe fecal metabolite composition in healthy participants in frozen stools. Frozen stool samples were collected from 10 healthy volunteers and cryogenically drilled in four areas along the specimen. Polar metabolites were analyzed using derivatization followed by two-dimensional gas chromatography and time of flight mass spectrometry. Lipids were detected using ultra high-performance liquid chromatography coupled with quadruple time-of-flight mass spectrometry. 2326 metabolic features were detected. Out of a total of 298 metabolites that were annotated we report here 185 that showed a technical variation of x < 30%. These metabolites included amino acids, fatty acid derivatives, carboxylic acids and phenolic compounds. Lipids predominantly belonged to the groups of diacylglycerols, triacylglycerols and ceramides. Metabolites varied between sampling areas, some were broadly homogeneous, others varied 80%. A LASSO-computed network using metabolites present in all areas showed two main clusters describing the system, DAG lipids and phenyllactic acid. In feces from healthy participants, the main groups detected were phenolic compounds, ceramides, diacylglycerols and triacylglycerols.

19.
J Diabetes Complications ; 34(1): 107467, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31676252

RESUMO

AIMS: To investigate levels and changes in diabetes distress over the course of the PRIORITY (Proteomic prediction and Renin angiotensin aldosterone system Inhibition prevention Of early diabetic nephRopathy In people with TYpe 2 diabetes and normoalbuminuria) randomised controlled trial of screening for diabetic kidney disease (DKD) risk among people with type 2 diabetes (T2D) at a specialist diabetes clinic in Denmark. METHODS: Of 436 trial participants with T2D, 216 were invited to complete the 17-item diabetes distress scale at the time of screening (T1, n = 180), immediately after receiving the screening results at 6-8 weeks (T2, n = 169), and at 12 months follow up (T3, n = 107). Linear mixed models were used to explore changes in diabetes distress. RESULTS: No significant changes in diabetes distress were observed between the time of screening, receiving results, and at 12 months. Changes in diabetes distress were not influenced by diabetes empowerment, sense of coherence, or perceived support for diabetes self-management. CONCLUSIONS: In contrast to previous studies demonstrating that screening programmes can have negative psychological consequences, our findings indicate that participating in this screening programme for DKD does not influence emotional burden or physician-related distress among people with T2D.

20.
Methods Mol Biol ; 2067: 287-306, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31701458

RESUMO

Molecular studies of the proteome and metabolome in readily available body fluids such as urine and blood performed in a comprehensive qualitative and quantitative way are a valuable source of information for kidney disease research. They provide potential biomarkers of disease progression, markers of efficacy of interventions, as well as information on the underlying pathophysiology. Identified proteins and metabolites may point to dysregulated biological pathways and this knowledge may be useful in the identification of new treatment targets.Many studies, focusing on chronic kidney disease as well as diabetic nephropathy, demonstrate that peptidome and metabolome analysis can substantially contribute to early detection and prediction of disease progression, but also stratification of kidney disease in clinical practice. An innovative, well-explored application of urinary peptidome analysis is the back-translation of results obtained in humans to animals, for animal model validation and improvement of the preclinical readouts. In this chapter, we provide an overview of urinary proteomic analysis with the CE-MS analytical platform, a strategy that has been successfully employed in several studies for the identification and validation of biomarkers in kidney diseases. We describe how to obtain the orthology between the animal model and humans. We also deliver an overview of the analysis of the metabolome with the GC×GC-TOF-MS and UHPLC-Q-TOF-MS analytical platforms for blood and serum as new methods being applied in kidney disease.It is expected that a systems medicine approach to kidney disease including multiple omics methods will provide us with the best way to understand and treat diabetic kidney disease in the future.

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