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Diabetic ketoacidosis (DKA) is a severe metabolic complication in children with newly diagnosed type 1 diabetes mellitus (T1DM) and may be associated with early injury of vital organs such as the kidneys and the heart. Early detection of organ dysfunction is important for identifying children at increased risk for complications.
This observational cross-sectional study aims to evaluate biomarkers of acute organ injury and associated clinical and echocardiographic parameters in children with newly diagnosed T1DM presenting with DKA, compared with children with newly diagnosed T1DM without DKA and healthy controls. Biomarkers including KIM-1, NGAL, high-sensitivity troponin, NT-proBNP, interleukin-6, and C-reactive protein will be measured during hospital admission and within the first 24-48 hours of hospitalization.
Diabetic ketoacidosis (DKA) is a common and potentially life-threatening metabolic complication in children with newly diagnosed type 1 diabetes mellitus (T1DM). In addition to the acute metabolic disturbances, DKA may lead to early or subclinical injury of vital organs, particularly the kidneys and the cardiovascular system, due to dehydration, hypovolemia, metabolic acidosis, electrolyte disturbances, and inflammatory activation.
Recent studies suggest that novel biomarkers may allow early detection of organ dysfunction before conventional clinical indicators become abnormal. Biomarkers such as kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), cystatin C, high-sensitivity troponin (hs-troponin), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) have been proposed as sensitive indicators of kidney and myocardial injury. Inflammatory markers such as interleukin-6 (IL-6) and C-reactive protein (CRP) may also reflect systemic inflammatory activation associated with metabolic decompensation.
The aim of this observational cross-sectional study is to investigate and compare biomarkers of acute organ injury and related clinical and echocardiographic parameters in children with newly diagnosed T1DM presenting with DKA, compared with children with newly diagnosed T1DM without DKA and healthy controls.
Participants will be categorized into three groups: (1) children with newly diagnosed T1DM presenting with DKA, (2) children with newly diagnosed T1DM without DKA, and (3) healthy children serving as controls. Blood samples will be collected at hospital admission for measurement of biomarkers including KIM-1, NGAL, hs-troponin, NT-proBNP, IL-6, and CRP, as well as standard laboratory parameters such as serum creatinine, cystatin C, albuminuria, pH, bicarbonate levels, and HbA1c.
All participants with T1DM will undergo cardiological evaluation including clinical examination, electrocardiogram, and transthoracic echocardiography with conventional measurements as well as advanced techniques such as tissue Doppler imaging and speckle-tracking echocardiography. Data collection will be performed at admission and within the first 24-48 hours of hospitalization.
The primary objective of the study is to compare biomarker levels and clinical parameters among the three study groups in order to identify early evidence of acute or subclinical organ dysfunction associated with diabetic ketoacidosis in children with newly diagnosed T1DM.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Newly Diagnosed T1DM with DKA | Children with newly diagnosed type 1 diabetes mellitus presenting with diabetic ketoacidosis at hospital admission. |
| |
| Newly Diagnosed T1DM without DKA | Children with newly diagnosed type 1 diabetes mellitus without diabetic ketoacidosis. |
| |
| Healthy Controls | Age-matched healthy children without diabetes serving as the control group. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Biomarker and Echocardiographic Assessment | Diagnostic Test | Blood and urine samples and echocardiographic evaluation performed as part of the clinical assessment of children with newly diagnosed type 1 diabetes. |
| Measure | Description | Time Frame |
|---|---|---|
| Neutrophil Gelatinase-Associated Lipocalin | Measurement of neutrophil gelatinase-associated lipocalin (NGAL, ng/mL) as a biomarker of early renal injury in children with newly diagnosed type 1 diabetes. | Within 48 hours of hospitalization |
| Kidney Injury Molecule-1 | Measurement of kidney injury molecule-1 (KIM-1, ng/mL) as a biomarker of renal injury in children with newly diagnosed type 1 diabetes. | Within 48 hours of hospitalization |
| High-Sensitivity Troponin | Measurement of high-sensitivity troponin (hs-troponin, ng/L) as a biomarker of myocardial injury in children with newly diagnosed type 1 diabetes. | Within 48 hours of hospitalization |
| N-terminal pro-B-type Natriuretic Peptide | Measurement of N-terminal pro-B-type natriuretic peptide (NT-proBNP, pg/mL) as a biomarker of cardiac stress in children with newly diagnosed type 1 diabetes. | Within 48 hours of hospitalization |
| Interleukin-6 | Measurement of interleukin-6 (IL-6, pg/mL) as a biomarker of systemic inflammation in children with newly diagnosed type 1 diabetes. | Within 48 hours of hospitalization |
| C-reactive Protein | Measurement of C-reactive protein (CRP, mg/L) as a biomarker of systemic inflammation in children with newly diagnosed type 1 diabetes. | Within 48 hours of hospitalization |
| Measure | Description | Time Frame |
|---|---|---|
| Serum Creatinine | Measurement of serum creatinine (mg/dL) in children with newly diagnosed type 1 diabetes. | Within 48 hours of hospitalization |
| Cystatin C | Measurement of and cystatin C (mg/L) in children with newly diagnosed type 1 diabetes. |
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Inclusion Criteria:
For control group:
- Age-matched healthy children without diabetes
Exclusion Criteria:
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Children aged 2-16 years admitted to the pediatric department with newly diagnosed type 1 diabetes mellitus, with or without diabetic ketoacidosis, as well as age-matched healthy children serving as controls.
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Athina Stamati | Contact | +30 6958796612 | atstamati@gmail.com |
| Name | Affiliation | Role |
|---|---|---|
| Athanasios Christoforidis | Aristotle University Of Thessaloniki | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hippokration General Hospital of Thessaloniki | Recruiting | Thessaloniki | Central Makedonia | Greece |
Individual participant data will not be shared due to privacy and data protection regulations and the presence of sensitive clinical information from pediatric participants.
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| ID | Term |
|---|---|
| D003922 | Diabetes Mellitus, Type 1 |
| D016883 | Diabetic Ketoacidosis |
| D058186 | Acute Kidney Injury |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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Blood and urine samples collected during hospital admission will be stored for the measurement of biomarkers related to acute organ injury, including KIM-1, NGAL, hs-troponin, NT-proBNP, IL-6, CRP, and cystatin C. Samples may be retained for future analyses related to the objectives of this study.
| Within 48 hours of hospitalization |
| Left Ventricular Ejection Fraction | Assessment of left ventricular systolic function using left ventricular ejection fraction measured by transthoracic echocardiography. | Within 48 hours of hospitalization |
| Left Ventricular Fractional Shortening | Evaluation of left ventricular systolic function using fractional shortening measured by transthoracic echocardiography. | Within 48 hours of hospitalization |
| E/e' Ratio | Assessment of left ventricular diastolic function using the ratio of transmitral early filling velocity (E) to tissue Doppler early diastolic velocity (e'). | Within 48 hours of hospitalization |
| Left Ventricular Global Longitudinal Strain | Assessment of subclinical left ventricular systolic function using global longitudinal strain derived from speckle-tracking echocardiography. | Within 48 hours of hospitalization |
| Glutamic Acid Decarboxylase Antibodies (GAD65) | Measurement of glutamic acid decarboxylase antibodies (GAD65) in children with newly diagnosed type 1 diabetes. | Within 48 hours of hospitalization |
| Insulin Autoantibodies (IAA) | Measurement of insulin autoantibodies (IAA) in children with newly diagnosed type 1 diabetes. | Within 48 hours of hospitalization |
| Islet Antigen-2 Antibodies (IA-2) | Measurement of islet antigen-2 antibodies (IA-2) in children with newly diagnosed type 1 diabetes. | Within 48 hours of hospitalization |
| Zinc Transporter 8 Antibodies (ZnT8) | Measurement of zinc transporter 8 antibodies (ZnT8) in children with newly diagnosed type 1 diabetes. | Within 48 hours of hospitalization |
| Severity of Diabetic Ketoacidosis | Classification of diabetic ketoacidosis severity at hospital admission based on venous blood pH and serum bicarbonate levels according to international pediatric guidelines. Diabetic ketoacidosis will be categorized as mild (pH <7.30, bicarbonate <15 mmol/L), moderate (pH <7.20, bicarbonate <10 mmol/L), or severe (pH <7.10, bicarbonate <5 mmol/L). | Baseline |
| D004700 | Endocrine System Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
| D007662 | Ketosis |
| D000138 | Acidosis |
| D000137 | Acid-Base Imbalance |
| D048909 | Diabetes Complications |
| D051437 | Renal Insufficiency |
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |