Hypothalamic-pituitary-adrenal axis activity is associated with the prevalence of chronic kidney disease in diabetic patients

Asao, Takako; Oki, Kenji; Yoneda, Masayasu; Tanaka, Junko; Kohno, Nobuoki

doi:10.1507/endocrj.ej15-0360

Cited by 24 publications

(21 citation statements)

References 44 publications

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“…In such a young population as ours, with a short history of disease, these findings would support an early origin of T1D‐related vascular damage to be further investigate trough long‐term follow‐up studies …”

Section: Discussionsupporting

confidence: 56%

Metabolomics reveals new metabolic perturbations in children with type 1 diabetes

et al. 2017

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Objective: Using an untargeted metabolomics approach we investigated the metabolome of children with type 1 diabetes (T1D) in comparison with healthy peers and explored the contribution of HbA1c and clinical features to the observed difference. Research Design and Methods:We enrolled children with T1D aged 6-15 years, attending the pediatric diabetes clinic of University of Padova (Italy). Healthy controls were enrolled on voluntary basis and matched for age, sex, pubertal status, body mass index (BMI). We performed a liquid chromatography and mass spectrometry analysis (LC-MS) on fasting urinary samples of the 2 groups.Results: A total of 56 patients with T1D aged (11.4 AE 2.2) years, and 30 healthy controls (10.7 AE 2.8) years were enrolled. We identified 59 urinary metabolites having a higher level in children with T1D, mainly represented by gluco-and mineralcorticoids, phenylalanine and tryptophan catabolites (kynurenine), small peptides, glycerophospholipids, fatty acids, and gut bacterial products. We did not find any association between HbA1c, pubertal status, disease duration, and metabolome profile within the case group.Conclusions: T1D profoundly disrupts the metabolome of pediatric patients. The excess of cortisol and aldosterone may contribute to the development of macrovascular complications in adulthood, while the increase of tryptophan derivates may have a role in neuronal damage associated to hyperglycemia. Determinants of such findings, other than HbA1c, should be explored. To date, the metabolome-based approach has demonstrated that, despite insulin treatment and a good glycemic control, in terms of In this study, we investigated a larger cohort by an untargeted metabolomics approach based on a different analytical platform (Ultra Performance Liquid Chromatography-Mass Spectrometry) able to detect thousand metabolites with 2 different polarity.The aim of this study was to investigate whether early metabolomic perturbations are detectable already in urinary metabolome of children with T1D when compared with healthy peers, in order to identify early markers of impaired metabolic pathways and generate novel hypothesis regarding the future complications described in adulthood.2 | METHODS | ParticipantsWe sequentially enrolled all pediatric patients with T1D admitted to | Sample preparationA 3 mL urine sample was collected from each subject enrolled and | Liquid chromatography and mass spectrometry analysis (LC-MS)The urine samples were analyzed with a Q-ToF Synapt G2high-resolution mass spectrometer interfaced with an Acquity Ultra Performance Liquid Chromatography (UPLC) (Waters Co., Milford, their ratio of mass on charge and retention time. A detailed description of the chromatographic analysis, and of the data pretreatment and processing is given in the Section 1 of Appendix S1, Supporting Information. | Statistical analysisMultivariate data analysis based on projection methods was applied to model the collected data. Specifically, exploratory data analysis was performed by Principal Componen...

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Section: Discussionsupporting

confidence: 56%

Metabolomics reveals new metabolic perturbations in children with type 1 diabetes

et al. 2017

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“…It is well established that whole body insulin sensitivity declines in obese children with normal compared to those with impaired glucose tolerance. 36 , 37 Importantly, obese children with IGT are uniformly markedly insulin resistant while those with NGT have insulin sensitivity levels ranging from highly sensitive to markedly resistant, similar to those with IGT. 38 Reduced insulin sensitivity in obese children is in most cases associated with a typical lipid partitioning profile generally characterized by increased intra-abdominal (visceral), intra-hepatic, and intramyocellular lipid deposition.…”

Section: Introductionmentioning

confidence: 99%

Prediabetes in youths: mechanisms and biomarkers

Weiss

Santoro

Giannini

et al. 2017

The Lancet Child & Adolescent Health

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Obesity has been estimated to decrease life expectancy by as little as 0.8 to as much as 7 years being the second leading cause of preventable death in the United States after smoking. Along with the increase in the prevalence of obesity, there has been a dramatic rise of the prevalence of prediabetes and type 2 diabetes among adolescents. Despite that, very little is known about the pathogenesis of these conditions in pediatrics and about how we could detect prediabetes in an early stage in order to prevent full blown diabetes. In this review we summarize the current knowledge on the pathophysiology of prediabetes and type 2 diabetes in adolescents and describe how biomarkers of beta-cell function might help identifying those individuals who are prone to progress from normal glucose tolerance towards prediabetes and overt type 2 diabetes. To better understand and fight this disease, we will need to explore and develop novel therapeutic strategies and individuate more sensitive and specific biomarkers that can allow an earlier detection of the disease.

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“…GC is known to cause deterioration in kidney function both directly by affecting glomerular and tubular function and indirectly by affecting the cardiovascular system (14). Excess GC due to endogenous GC overproduction in PAHC plays a pivotal role in hypertension and causes increased cardiac output, total peripheral resistance, and renal blood flow (9). Focusing on the effect of GC on the kidney, GCs increased renal vascular resistance in the general population (15), and chronic GC exposure may decrease GFR and lead to a higher cardiovascular risk in patients with PAHC (14).…”

Section: Discussionmentioning

confidence: 99%

“…In fact, some clinical investigations showed the negative effect of GC on kidney function in the general population. In diabetic patients, autonomous cortisol secretion affected kidney function negatively in a dose-dependent manner (9). Serum cortisol level was measured after overnight dexamethasone suppression at a dose of 1 mg and significantly correlated with worse estimated glomerular filtration rate (eGFR) and spot urine albumin to creatinine ratio.…”

Section: Introductionmentioning

confidence: 99%

Overweight Patients Less Improved Kidney Function After Laparoscopic Surgery for Adrenocortical Adenoma With Excess Cortisol Secretion

et al. 2019

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Purpose: Glucocorticoid (GC) is known to be involved in the deterioration of kidney function both directly by affecting the glomeruli and renal tubules and indirectly by affecting cardiovascular function. Autonomous GC secretion is the main feature of primary adrenal hypercortisolism (PAHC). However, the ideal treatment option (operation vs. medical treatment and observation) for patients with PAHC has not been established yet. In this study, we assessed a time series of kidney function in patients with PAHC treated via laparoscopic adrenalectomy and investigated the predictive factors for kidney function 1 year after surgery. Methods: From September 1997 to July 2017, 175 laparoscopic adrenalectomies were performed for adrenal tumors at Akita University. Thirty patients, who were diagnosed as having PAHC via preoperative endocrinological evaluations and followed up for at least 1 year after surgery, were included in this study. Patients with severe complications or simultaneous aldosteronism were excluded. The mean age of the 30 patients was 57.5 years (range, 33–79 years; males, 4; females, 26), and the right and left sides were affected in 9 and 21 patients, respectively. Results: In all, 18 patients were diagnosed as having Cushing's syndrome and 12 as having subclinical Cushing's syndrome. The steroid cover was required in all cases after surgery. The estimated glomerular filtration rate significantly improved (78.4 mL/min [64.8–95.8] vs. 84.1 mL/min [66.8–104.0], p = 0.012) 1 year after surgery. Patients showing 5% or more improvement in kidney function and those showing less than 5% improvement were compared. On performing univariate analyses, factors such as a longer operative time, heavy body mass index (BMI), and preoperative unsuppressed ACTH were associated with worse improvement in kidney function. No significant associations were observed regarding metabolic disorders, clinical symptoms, and gross proteinuria. On multivariate analysis, patients with a higher BMI (≥ 24 kg/m 2 ) showed worse improvement in kidney function at 1 year after surgery (odds ratio 14.0, 95% confidence interval 1.3–142.9, p = 0.012). Conclusions: In PAHC patients, after 1 year of follow-up, kidney function improved in terms of estimated glomerular filtration rate. Therefore, this improvement seems to be delayed in overweight patients, suggesting its direct role in renal function.

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Hypothalamic-pituitary-adrenal axis activity is associated with the prevalence of chronic kidney disease in diabetic patients

Cited by 24 publications

References 44 publications

Metabolomics reveals new metabolic perturbations in children with type 1 diabetes

Metabolomics reveals new metabolic perturbations in children with type 1 diabetes

Prediabetes in youths: mechanisms and biomarkers

Overweight Patients Less Improved Kidney Function After Laparoscopic Surgery for Adrenocortical Adenoma With Excess Cortisol Secretion

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