Ioanna Kosteria

Plasma Metabolomic Profiling Suggests Early Indications for Predisposition to Latent Insulin Resistance in Children Conceived by ICSI

Background There have been increasing indications about an epigenetically-based elevated predisposition of assisted reproductive technology (ART) offspring to insulin resistance, which can lead to an unfavorable cardio-metabolic profile in adult life. However, the relevant long-term systematic molecular studies are limited, especially for the IntraCytoplasmic Sperm Injection (ICSI) method, introduced in 1992. In this study, we carefully defined a group of 42 prepubertal ICSI and 42 naturally conceived (NC) children. We assessed differences in their metabolic profile based on biochemical measurements, while, for a subgroup, plasma metabolomic analysis was also performed, investigating any relevant insulin resistance indices. Methods & Results Auxological and biochemical parameters of 42 6.8±2.1 yrs old ICSI-conceived and 42 age-matched controls were measured. Significant differences between the groups were determined using univariate and multivariate statistics, indicating low urea and low-grade inflammation markers (YKL-40, hsCRP) and high triiodothyronine (T3) in ICSI-children compared to controls. Moreover, plasma metabolomic analysis carried out for a subgroup of 10 ICSI- and 10 NC girls using Gas Chromatography-Mass Spectrometry (GC-MS) indicated clear differences between the two groups, characterized by 36 metabolites linked to obesity, insulin resistance and metabolic syndrome. Notably, the distinction between the two girl subgroups was accentuated when both their biochemical and metabolomic measurements were employed. Conclusions The present study contributes a large auxological and biochemical dataset of a well-defined group of pre-pubertal ICSI-conceived subjects to the research of the ART effect to the offsprings health. Moreover, it is the first time that the relevant usefulness of metabolomics was investigated. The acquired results are consistent with early insulin resistance in ICSI-offspring, paving the way for further systematic investigations. These data support that metabolomics may unravel metabolic differences before they become clinically or biochemically evident, underlining its utility in the ART research.

NGAL and cystatin C: two possible early markers of diabetic nephropathy in young patients with type 1 diabetes mellitus: one year follow up.

OBJECTIVEDiabetic nephropathy constitutes a major long-term complication in patients with type 1 diabetes mellitus (T1D) and its diagnosis is based on microalbuminuria. The aim of this observational follow-up study was to explore the role of neutrophil-gelatinase-associated lipocalin (NGAL) and cystatin C in unravelling early diabetic nephropathy even in patients with normoalbuminuria.DESIGNFifty-six euthyroid patients with T1D, with mean age 13.1 (SD: 3.2) years, and 49 healthy controls with mean age 12.8 (SD: 6.6) were recruited. Besides standard blood chemistry and urinary albumin excretion, serum NGAL (ELISA) and cystatin C (nephelometry) were measured at enrollment and after 12–15 months. GFR was calculated with the bedside Schwartz formula (eGFR) and the Lund strategy formula (L-eGFR).RESULTSAt baseline, mean NGAL levels were not significantly different between children with diabetes and controls. At re-evaluation, mean NGAL value and mean eGFR value in patients with diabetes were increased (p = 0.032 and p = 0.003 respectively). At both baseline and reevaluation, NGAL was positively correlated with cystatin C (r=0.41, p<0.001), systolic arterial pressure z-score (r=0.3, p = 0.031) and creatinine (r=0.32, p = 0.010). NGAL correlated negatively with eGFR (r=−0.26, p = 0.049) and L-eGFR (r=−0.33, p = 0.010). Cystatin C had a negative correlation to eGFR (r=−0.29, p = 0.025) and a positive one with creatinine (r=0.35, p = 0.009) at reevaluation. No statistically significant correlation was found between cystatin C and microalbuminuria (p = 0.736).CONCLUSIONSNGAL and cystatin C, known markers of renal injury, correlate with renal function decline in T1D, suggesting that they may be used as supplementary tests to urine albumin excretion in order to unmask early renal dysfunction.

Possibilities and challenges of a large international benchmarking in pediatric diabetology—The SWEET experience

Despite the existence of evidence‐based guidelines for the care of children with diabetes, widespread gaps in knowledge, attitude, and practice remain. The purpose of this paper is to present a review of benchmarking practices and results of this process within SWEET, moreover focusing on current challenges and future directions.

The influence of treatment, age at onset, and metabolic control on height in children and adolescents with type 1 diabetes-A SWEET collaborative study

To describe the association between height, demographics, and treatment in youths with type 1 diabetes participating in an international network for pediatric diabetes centers (SWEET).

Pediatric endocrine and metabolic diseases and proteomics

The principles of Predictive, Preventive and Personalized Medicine (PPPM) dictate the need to recognize individual susceptibility to disease in a timely fashion and to offer targeted preventive interventions and treatments. Proteomics is a state-of-the art technology- driven science aiming at expanding our understanding of the pathophysiologic mechanisms that underlie disease, but also at identifying accurate predictive, diagnostic and therapeutic biomarkers, that will eventually promote the implementation of PPPM. In this review, we summarize the wide spectrum of the applications of Mass Spectrometry-based proteomics in the various fields of Pediatric Endocrinology, including Inborn Errors of Metabolism, type 1 diabetes, Adrenal Disease, Metabolic Syndrome and Thyroid disease, ranging from neonatal screening to early recognition of specific at-risk populations for disease manifestations or complications in adult life and to monitoring of disease progression and response to treatment. SIGNIFICANCE Proteomics is a state-of-the art technology- driven science aiming at expanding our understanding of the pathophysiologic mechanisms that underlie disease, but also at identifying accurate predictive, diagnostic and therapeutic biomarkers that will eventually lead to successful, targeted, patient-centric, individualized approach of each patient, as dictated by the principles of Predictive, Preventive and Personalized Medicine. In this review, we summarize the wide spectrum of the applications of Mass Spectrometry-based proteomics in the various fields of Pediatric Endocrinology, including Inborn Errors of Metabolism, type 1 diabetes, Adrenal Disease, Metabolic Syndrome and Thyroid disease, ranging from neonatal screening, accurate diagnosis, early recognition of specific at-risk populations for the prevention of disease manifestation or future complications.