Recunoașatere tardivă a debutului diabetului zaharat tip 1, complicat cu cetoacidoză diabetică si asociat cu tiroidită autoimună-prezentare de caz

Rezumat

Recunoașterea întârziată și trimiterea la evaluare a unui copil cu suspiciune de diabet zaharat tip 1(DZ tip 1) poate conduce la cetoacidoză diabetică (CAD) cu consecințe imediate și pe termen lung asupra sănătății copilului. Cetoacidoză diabetică (CAD) reprezintă o complicație acută severă care apare frecvent înainte de diagnosticarea DZ tip 1. Incidența CAD că și formă de debut a DZ tip 1 a copiilor și adolescenților în diferite țări în ultima decadă variază de la 14.7% în Denmarca la 79.8% în Arabia Saudită. Ea este considerate încă înalta, deși un anumit declin a fost totuși înregistrat. Un studiu recent, prospectiv, observațional al CAD la debutul DZ tip 1 în 31 țări a clasat România printre cele cu frecventele cele mai înalte. Prezentăm un caz clinic al unei fetițe cu debut insidious de DZ tip 1, precipitat de o infecție acută a cailor respiratorii, complicat cu CAD și asociat cu o altă boală autoimună de la debutul acestuia.

Concluzie. Acest caz atrage atenția asupra nevoii de recunoaștere precoce de către medicii de familie a acestei patologii serioase a copiilor, care trebuie să se focuseze mai intens pe educația părinților privind aderența la examenele de bilanț și recunoaștere a primelor semne de boală. Există o necesitate de recunoaștere de către părinți și profesioniștii din asistență medicală primară a simptomelor diabetului, avînd în vedere prezentarea tîrzie și trimiterea intirziata pentru evaluări și intervenții care pot reduce excesul de morbiditate și mortalitate a acestei patologii.

Cuvinte cheie: diabet zaharat tip 1, copii, recunoaștere întârziată, cetoacidoza diabetică

 


RUBRICA DISCIPLINEI MEDICINA DE FAMILIE UMF „Iuliu Hațieganu” CLUJ-NAPOCA ȘI A ASOCIAȚIEI MEDICILOR DE FAMILIE CLUJ

Delayed recognition of new onset type 1 diabetes mellitus complicated with ketoacidosis and associated with autoimmune thyroiditis-a case report

Case report

Abstract

Delayed recognition and referral of the new onset type 1 diabetes mellitus (T1DM) can lead to diabetic ketoacidosis (DKA) with potentially harmful consequences. Diabetic ketoacidosis (DKA) represents a severe acute complication frequently occurring before the first diagnosis of T1DM. The rates of DKA of new-onset T1DM in children and adolescents in different countries available over the last decade varied from 14.7% (Denmark) to 79.8% (Saudi Arabia). DKA rates are still high, but a decline can also be recognized. A recent prospective observational study of diabetic ketoacidosis at onset of Type 1 diabetes in 31 countries rated Romania among those with highest frequencies of DKA at T1DM diagnosis. We present the unrecognized insidious onset of T1DM precipitated by acute respiratory virus, complicated with diabetic ketoacidosis (DKA), and the association of an autoimmune disease since the onset of the disease.

Conclusion. This case report draws attention to the need for early recognition of this serious pathology of children by family doctors, which should strengthen parents’ education for taking children’s balance tests and awareness of the first signs of illness. There is a need for increased awareness of the symptoms of diabetes among parents and primary care professionals, given the delayed presentation and delayed referral by general practitioners for future interventions to reduce this excess morbidity and mortality.

Keywords: type 1 diabetes mellitus, children, delayed recognition, diabetic ketoacidosis

Introduction

Type 1 diabetes mellitus is the most frequent endocrine disease in children, with 65,000 children diagnosed worldwide every year. Up to 80% of these children present with diabetic ketoacidosis (DKA), which is associated with both short-term risks and long-term consequences (1). Delayed recognition and referral of the new onset type 1 diabetes mellitus (T1DM) can lead to diabetic ketoacidosis (DKA) with potentially harmful consequences. Delayed referral was defined as a primary healthcare contact due to diabetes-related symptoms 0-4 weeks before hospital admission without immediate referral, or registered elevated glucose levels at primary healthcare centers without immediate referral (2).

Type 1 diabetes is an autoimmune disease characterized by immune-mediated self-destruction of pancreatic beta cells in a chronic inflammatory process. The detection of autoimmunity markers (auto Ac GAD, IAA, ICA, etc.) is a clear proof in favor of this mechanism. The approximately 50 genes susceptible to diabetes carry a high risk of developing other autoimmune diseases at the same time or at a distance from the onset of diabetes.

There is often a tendency for family aggregation for autoimmune diseases, which is an additional argument in favor of genetic predisposition. Over time, other glandular autoimmune diseases (e.g. autoimmune thyroiditis, Addison’s disease) or non-endocrine disorders (e.g. celiac disease, autoimmune gastritis/pernicious anemia, vitiligo, rheumatoid arthritis) may be associated. Early detection of specific autoantibodies and latent organic damage allow for early therapeutic measures to prevent the worsening of autoimmune disease and the decompensation of diabetes (3).

Diabetic ketoacidosis (DKA) is defined as a severe metabolic imbalance resulting from insulin deficiency and concomitant decrease in fluids and electrolytes. It is a complication of type 1 diabetes and possible in type 2 diabetes as well.

The diagnostic criteria for ketoacidosis are: hyperglycemia 11 mmol/l (>200 mg/dl), venous pH <7.3 or Bicarbonate <15 mmol/l, ketonemia or ketonuria (4).

Case report

The disease of a 5-year-old girl began insidiously 1 month before hospitalization with polyuria, polydipsia, weight loss (5 kg in 4 weeks), fatigue and drowsiness, subsequently associating clinical signs of respiratory viral infection. At presentation in the emergency department the child had altered general condition, wrinkled facies, dry lips, angular cheilitis, dry skin and lips, acetonemic breath, Kussmaul respiration, polyuria, polydipsia.

Para clinical examinations in the Emergency Department were blood glucose: 460 mg/dl, pH =7.1, HCO3=8.1 mmol/l, BE= -23 mmol/l, Na=129 mEq/l, Ketonemia=6.1 mmol/l, Glycosuria +++, Ketonuria +++.

Diagnosis established in Emergency Department was Type 1 diabetes mellitus complicated with inaugural diabetic ketoacidosis.

Case Management. Parenteral hydro electrolytic rebalancing therapy and continuous rapid insulin replacement were performed. During the hospitalization the para clinical investigations were continued. After restoration of digestive tolerance and improvement of metabolic acidosis, replacement therapy with insulin analogues was administered subcutaneously. Administration, in 4 doses/day, with a requirement of 1 IU insulin/kg/day: Novorapid and Levemir. The caloric requirement was established according to appetite: 1600 kcal/day, of which 220 g carbohydrates, 60 g protein and 54 g lipids, distributed in 3 main meals and 3 snacks.

During the hospitalization in the Pediatric Clinic, she presented acute complications of diabetes, manifested by critical cerebral crises in the context of severe hypoglycemia (glycaemia 40 mg/dl), with remission after administration of glucose iv. Subsequently, the blood glucose returned to normal values during hospitalization, the ketonemia decreased to 2.9-0.2 mmol/l. At discharge glycosuria and ketonemia become negative.

The glycosylated hemoglobin HbA1c=11.1 %; Peptide C=0.151 ng/ml; Antibody GAD-II: 10 kU/ml; Anti-tyrosine phosphatase IA2=0.66k U/ml; Beta Insular Cells Antibody ICA=1:<10; Anti TPO=104 IU/ml; TSH = 3.05 uIU/ml; FreeT4 = 1.08 ng/dl and Transglutaminase IgA Antibodies were negative. These examinations confirmed the diagnosis of type 1 diabetes mellitus, stage III of metabolic decompensation (hyperglycemia, ketonemia, glycosuria, ketonuria, decompensated metabolic acidosis, hyponatremia). The high value of glycosylated hemoglobin confirms the hyperglycemic status of approximately 3 months prior to hospitalization. The low level of Peptide C showed low reserve of pancreatic beta cells that leads to Type 1 Diabetes mellitus and the presence of pancreatic autoantibodies (anti GAD) confirms the autoimmune etiopathogenesis.

The possible association with other autoimmune diseases was also evaluated. Autoimmune thyroiditis was confirmed by positive anti TPO with normal thyroid function and normal size, volume and structure at thyroid ultrasound.  Gluten enteropathy (celiac disease) has been clinically, and para clinically refuted by transglutaminase negative antibodies.

Discussion

The rates of DKA of new-onset T1DM in children and adolescents in different countries available over the last decade varied from 14.7 % (Denmark) to 79.8 % (Saudi Arabia). DKA rates are still high, but a decline can also be recognized in 2018 (5).

A recent Swedish prospective observational study of diabetic ketoacidosis at onset of Type 1 diabetes included 237 patients, among which parental suspicion of new-onset diabetes before healthcare contacts was reported in 39 %. Parental suspicion of diabetes was associated with higher pH values at diagnosis. Patients in contact with primary health care providers before hospital admission had a delayed referral in 43 % of the cases. Delayed referral was associated with lower pH values at hospital admission. Parental suspicion of diabetes was associated with milder DKA at hospital admission. Delayed referral was seen in a considerable proportion of children with primary healthcare contacts for symptoms associated with diabetes (2).

A systematic review about the variation between countries in the frequency of diabetic ketoacidosis at first presentation of type 1 diabetes in children included 31 countries. The frequency of DKA at diagnosis ranged from 12.8 % to 80 %, with highest frequencies in the United Arab Emirates, Saudi Arabia and Romania, and the lowest in Sweden, the Slovak Republic and Canada. Multivariable modelling showed the frequency of DKA was inversely associated with gross domestic product, latitude and background incidence of type 1 diabetes. This study demonstrates large variations that may, at least in part, be explained by different levels of disease awareness and healthcare provision and suggests ways to decrease the excess morbidity and mortality associated with DKA at diagnosis (1). Unfortunately, Romania was rated in 2012 among the countries with the highest frequencies of diabetic ketoacidosis at the first presentation of type 1 diabetes in children, a situation that continues to persist as evidenced by this case report.

Due to modern treatment strategies: insulin pumps coupled with continuous blood glucose self-monitoring (CGMS), diabetes monitoring and treatment has become much easier for children and young people with type 1 diabetes in Romania. Family doctors should be trained to contribute with diabetologists and pediatricians to the specific education of diabetic children and their parents both in self-monitoring of blood glucose and in the prevention of long-term complications. Pancreatic beta cell transplantation is feasible, but currently the results are unsatisfactory, and many multicenter studies are underway and will lead to better results.

Case report’s particularities. The insidious onset of T1DM precipitated by acute respiratory virus and the association of an autoimmune disease since the onset of the disease are the particularities of this clinical case.

Conclusion

This case report draws attention to the need for early recognition of this serious pathology of children by family doctors, which should strengthen parents’ education for taking children’s balance tests and awareness of the first signs of illness.

 

Conflict of interst: none/Conflict de interese: nu există

Acknowledgments: All authors contributed equally to this article/ Toţi autorii au avut contribuţie egală la acest articol

       References/Bibliografie

  1. Usher-Smith JA, Thompson M, Ercole A, Walter FM. Variation between countries in the frequency of diabetic ketoacidosis at first presentation of type 1 diabetes in children: a systematic review. Diabetologia. 2012;55(11):2878-94. Available from: doi: 10.1007/s00125-012-2690-2.
  2. Wersäll JH, Adolfsson P, Forsander G, Ricksten SE, Hanas R. Delayed referral is common even when new-onset diabetes is suspected in children. A Swedish prospective observational study of diabetic ketoacidosis at onset of Type 1 diabetes. Pediatr Diabetes. 2021;22(6):900-908. Available from: doi: 10.1111/pedi.13229.
  3. ISPAD Clinical Practice Consensus Guidelines 2018. Available from: https://www.ispad.org/page/ISPADGuidelines2018 [Accessed 5th September 2021].
  4. ISPAD Clinical Practice Consensus Guidelines 2018. Diabetic ketoacidosis and the hyperglycemic hyperosmolar state. Available from:https://doi.org/10.1111/pedi.12701.
  5. Große J, Hornstein H, Manuwald U, Kugler J, Glauche I, Rothe U. Incidence of Diabetic Ketoacidosis of New-Onset Type 1 Diabetes in Children and Adolescents in Different Countries Correlates with Human Development Index (HDI): An Updated Systematic Review, Meta-Analysis, and Meta-Regression. Horm Metab Res. 2018;50(3):209-222. Available from: doi: 10.1055/s-0044-102090.

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