RESUMO
AIMS/HYPOTHESIS: High intraglomerular pressure causes renal inflammation in experimental models of diabetes. Our objective was to determine whether renal hyperfiltration, a surrogate for intraglomerular hypertension, is associated with increased excretion of urinary cytokines/chemokines in patients with type 1 diabetes mellitus. METHODS: Blood pressure, renal haemodynamic function (inulin and para-aminohippurate clearances for glomerular filtration rate (GFR) and effective renal plasma flow (ERPF), respectively) and urine samples were obtained during clamped euglycaemia in individuals with type 1 diabetes with either hyperfiltration (GFR determined using inulin [GFRINULIN] ≥ 135 ml min⻹ 1.73 m⻲, n = 28) or normofiltration (n = 21) and healthy control individuals (n = 18). RESULTS: Baseline clinical characteristics, dietary sodium and protein intake and blood pressure levels were similar in the diabetic and healthy control groups. In addition, HbA1c levels were similar in the two diabetic groups. As expected baseline GFR was higher in hyperfilterers than either normofiltering diabetic patients or healthy control patients (165 ± 9 vs 113 ± 2 and 116 ± 4 ml min⻹ 1.73 m⻲, respectively, p < 0.01). ERPF and renal blood flow were also comparatively higher and renal vascular resistance was lower in hyperfiltering patients (p < 0.01). Hyperfiltering diabetic patients had higher excretion rates for eotaxin, IFNα2, macrophage-derived chemokine, platelet-derived growth factor (PDGF)-AA, PDGF-AB/BB and granulocyte-macrophage colony-stimulating factor (p ≤ 0.01). Urinary monocyte chemoattractant protein (MCP)-1 and RANTES (regulated on activation, normal T expressed and secreted) excretion was also higher in hyperfiltering vs normofiltering diabetic individuals (p < 0.01) and fibroblast growth factor-2, MCP-3 and CD40K excretion was elevated in hyperfiltering diabetic individuals vs healthy controls (p < 0.01). CONCLUSIONS/INTERPRETATION: Renal hyperfiltration is associated with increased urinary excretion of inflammatory cytokines/chemokines in patients with uncomplicated type 1 diabetes.
Assuntos
Quimiocinas/urina , Citocinas/urina , Diabetes Mellitus Tipo 1/complicações , Nefropatias Diabéticas/fisiopatologia , Barreira de Filtração Glomerular/fisiopatologia , Regulação para Cima , Adulto , Biomarcadores/urina , Estudos de Coortes , Nefropatias Diabéticas/diagnóstico , Nefropatias Diabéticas/imunologia , Nefropatias Diabéticas/urina , Diagnóstico Precoce , Feminino , Barreira de Filtração Glomerular/imunologia , Taxa de Filtração Glomerular , Técnica Clamp de Glucose , Humanos , Masculino , Projetos Piloto , Circulação Renal , Índice de Gravidade de Doença , Adulto JovemRESUMO
AIMS: Patients with the highest albumin:creatinine ratio within the normal range are at an increased risk for developing microalbuminuria. The mechanistic basis for this is unknown, but may be related to renal inflammation. Our goal was to characterize the urinary excretion of cytokines/chemokines in normoalbuminuric adolescents with Type 1 diabetes to determine whether higher range normoalbuminuria is associated with evidence of renal inflammation. METHODS: Forty-two urinary cytokines/chemokines were measured in subjects who were screened for the Adolescent Type 1 Diabetes Cardio-Renal Intervention Trial. Urinary cytokines/chemokines were compared across low (n = 50), middle (n = 50) or high (n = 50) albumin:creatinine ratio tertile groups. RESULTS: At baseline, participants in the upper tertile were younger and had shorter diabetes duration compared with the other groups. Other clinical characteristics were similar. Urinary levels of interleukin 6, interleukin 8, platelet-derived growth factor-AA and RANTES differed across albumin:creatinine ratio tertiles, with higher values in patients in the middle and high tertiles compared with the lower tertile (ANCOVA P ≤ 0.01). CONCLUSIONS: Within the normal albumin:creatinine ratio range, higher urinary albumin excretion is associated with elevated urinary levels of inflammatory markers. Ultimately, this may provide mechanistic insights into disease pathophysiology and stratify the risk of nephropathy in Type 1 diabetes.
Assuntos
Albuminúria/urina , Diabetes Mellitus Tipo 1/urina , Nefropatias Diabéticas/urina , Inflamação/urina , Adolescente , Albuminúria/patologia , Biomarcadores/urina , Quimiocinas/urina , Criança , Creatina/urina , Citocinas/urina , Diabetes Mellitus Tipo 1/patologia , Nefropatias Diabéticas/patologia , Progressão da Doença , Método Duplo-Cego , Feminino , Humanos , Masculino , Fatores de RiscoRESUMO
Understanding motivational drivers and barriers to patient participation in diabetes research are important to ensure research is relevant and valuable. Young adults with type 1 diabetes (T1D) completed a 31-question qualitative survey evaluating participant experience, understanding, and motivators and barriers to research involvement. A total of 35 participants, 19-28 years of age, 60% female, completed the survey. Motivating factors included personal benefit, relationship with the study team, curiosity, financial compensation, altruism, and nostalgia. Older participants (>22 years) reported higher levels of trust in the study team (p = 0.02) and their relationship with the study team positively influenced their decision to participate (p = 0.03). Financial compensation was a strong motivator for participants with higher education (p = 0.02). Age, sex, education level, and trust in the study team influenced participants' understanding. Barriers included logistics and lack of familial support. Important motivational drivers and barriers to participation in research by young adults with T1D must be considered to increase research engagement and facilitate the discovery of new knowledge.