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Table of Contents
Year : 2018  |  Volume : 11  |  Issue : 2  |  Page : 81-83

Transient neonatal diabetes in extremely low-birth-weight baby treated with long-acting insulin (Glargine)

1 Department of Paediatrics, Neonatal Intensive Care Unit, Dubai Hospital, Dubai, United Arab Emirates
2 Department of Paediatrics, Paediatric Endocrinology Unit, Dubai Hospital, Dubai, United Arab Emirates

Date of Web Publication26-Jun-2018

Correspondence Address:
Khalid Iqbal
Department of Paediatrics, Neonatal Intensive Care Unit, Dubai Hospital, Dubai
United Arab Emirates
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/HMJ.HMJ_14_18

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Neonatal diabetes mellitus (NDM) is not uncommon amongst extreme preterm or extremely low-birth-weight (ELBW) neonates. The treatment for NDM to achieve normoglycemia is not without challenges because of lack of one ideal strategy for appropriate treatment. The management of NDM begins with insulin, but it is very difficult to adjust the doses and route of administration because of the dilemma of frequently developing hypoglycaemia and then hyperglycaemia again after stopping insulin. We report here an ELBW baby initially treated with regular insulin and then glargine, long-acting insulin, was administered subcutaneously as once daily dose with successful control of hyperglycaemia. Previously, two cases have been reported where glargine was used to control NDM. The possibility of recommendation for successful treatment with subcutaneous long-acting insulin to treat NDM amongst ELBW neonates is discussed.

Keywords: Diabetes, extremely low birth weight, glargine, hypoglycemia, neonatology

How to cite this article:
Galal M, Iqbal K, Khan A, Malallah AJ, Hassan MA, Khan W. Transient neonatal diabetes in extremely low-birth-weight baby treated with long-acting insulin (Glargine). Hamdan Med J 2018;11:81-3

How to cite this URL:
Galal M, Iqbal K, Khan A, Malallah AJ, Hassan MA, Khan W. Transient neonatal diabetes in extremely low-birth-weight baby treated with long-acting insulin (Glargine). Hamdan Med J [serial online] 2018 [cited 2022 Jan 20];11:81-3. Available from: http://www.hamdanjournal.org/text.asp?2018/11/2/81/235229

  Introduction Top

Neonatal diabetes mellitus (NDM) is broadly defined as persistent hyperglycaemia within the 1st month of life lasting at least 2 weeks and requiring management with insulin.[1] NDM is a rare disease, results from impaired insulin secretion and presents with persisting hyperglycaemia requiring insulin treatment. Usually, the neonatologists face challenges with regard to the management either by intermittent intravenous insulin or as continuous infusion to achieve normoglycaemia according to the common guidelines used by most of the units.[1],[2],[3]

NDM is subclassified into transient NDM (TNDM) or permanent NDM (PNDM). The diagnosis of TNDM versus PNDM is not typically clear initially as a result of similar presenting symptoms and often requires further workup. The course of TNDM is highly variable, ranging from permanent resolution within the first several weeks or months of life to recurrence later in childhood.

Management of NDM begins with insulin; however, the correct dose, choice of formulation and route of administration are complicated by the risk of neonatal hypoglycaemia that is common, especially amongst extremely preterm babies.[4] Usually, management of hyperglycaemia in this category of extremely low-birth-weight (ELBW) babies remains challenging and difficult because of adjustment of doses and development of hypoglycaemia. Routinely, regular insulin (Humulin R) either as intravenous bolus or intravenous continuous infusion is the mode of treating hyperglycaemia amongst neonates, and long-acting insulin is not considered as the choice of treatment because of the paucity of subcutaneous fat (especially in low-birth-weight infants), the minute doses of insulin required and in particular the high risk of hypoglycaemia.[5] There are very few cases of ELBW neonates reported so far treated successfully with the long-acting subcutaneous insulin analogue, glargine. We report here an ELBW baby initially treated with regular insulin and then glargine was administered subcutaneously with successful control of hyperglycaemia.

  Case Report Top

This female baby was born preterm at 24 weeks plus 6 days of gestation, birth weight was 620 g, born by normal vaginal delivery to primi mother with premature rupture of membrane. This mother conceived by in vitro fertilisation and received two doses of betamethasone. Mother was not diabetic and had no other risk factor.

The baby was born limp and needed resuscitation with bag and mask ventilation and chest compression. Apgar score was 0 at 1 min, 4 at 5 min and 8 at 10 min. The baby was intubated and connected to mechanical ventilator. The baby was treated for respiratory distress syndrome and received surfactant.

On day 3 of life, she developed hyperglycaemia with blood sugar values above 300 mg/dl, so she was given insulin intravenously as boluses on dose started with 0.05 U/Kg and then increased to 0.075 U/kg/dose. After two boluses, blood sugar level remained high >250 mg/dl, and according to our departmental protocol, the baby was started on insulin infusion with doses from 0.01 to 0.05 U/kg/hr. After control of blood sugar, the doses were titrated accordingly, but the baby developed hypoglycaemia even after reducing the dose and eventually, insulin infusion was stopped. Just after few hours after stopping insulin, the baby started having high blood sugar to >250 mg/dl. This time two more doses of insulin given as intravenous boluses still hyperglycaemia not controlled; therefore, insulin infusion was started and doses were increased gradually to 0.1 U/Kg/h to achieve normoglycaemia, and as blood sugar level dropped down to <200 mg/dl, insulin doses were reduced gradually, but at the same time, blood dropped to 40 mg/dl. After stopping insulin infusion, blood sugar remained normal for a day and again started rising to >200 mg/dl.

During the third episode of hyperglycaemia, blood sugar level increased to >280 mg/dl. She was started on insulin infusion due to persistent hyperglycaemia (>250 mg/dl) with infusion rate from 0.01 to 0.05 U/kg/h, and sugar level was ranging from 150 to 280 mg/dl. However, due to hypoglycaemia again, the insulin infusion stopped.

The baby was receiving total parenteral nutrition with glucose intake of 4 mg/kg/min till baby was on full feeds by 2 weeks of age.

After three episodes of hyperglycaemia and unsuccessful use of insulin, baby continued to have high sugar ranging >270 mg/dl, while the baby was on full feeds with fortified expressed breast milk. This time paediatric endocrinologist was consulted and this time long-acting insulin, glargine (0.5 U/kg subcutaneous once/day), was started [Table 1]. The response to glargine was better, and blood sugar levels gradually controlled to normal level (150 to 200 mg/dl). The dose of glargine was tapered and stopped after 16 days due to resolved hyperglycaemia. All investigations sent were normal.
Table 1: Laboratory results

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The baby was discharged home after lengthy hospital stay because baby remained ventilated for long time and then was on non-invasive ventilation mode. She was kept on ventilator for 62 days due to chronic lung disease and unsuccessful trials of extubation. She was oxygen dependent until weaned from oxygen at the age of 87 days. She had an episode of clinical deterioration, septic workup revealed high C-reactive protein and was treated with antibiotics. Subsequently, the baby improved, but still, she was on nasogastric tube feeding and gradually started sucking. The breastfeeding was tried and established slowly and was discharged at the age of 5 months. On discharge, she was breastfeeding well with normal blood sugar levels. She is being followed up with paediatric endocrinology team. Her weight on discharge was 4.27 kg.

  Discussion Top

Hyperglycaemia is not uncommon amongst extremely preterm and ELBW babies. Nevertheless, management of severe hyperglycaemia amongst these ELBW neonates is never without challenges. Due to the paucity of subcutaneous fat and muscles in these tiny ELBW babies, regular insulin is routinely used intravenously, initially as boluses and in case of persistent or uncontrolled hyperglycaemia, insulin infusion is tried. This usually leads to the dilemma of either hypoglycaemia or hyperglycaemia again after stopping insulin. We faced the same frustrating situation of developing severe hypoglycaemia (20 mg/dl–30 mg/dl) requiring intravenous glucose boluses after slowly increasing the dose of infusion according to blood sugar levels and then gradually developing hyperglycaemia (>250 mg/dl) after stopping insulin infusion. This cycle of hyperglycaemia followed by hypoglycaemia with insulin administration led to an uncertain condition where we were unable to achieve the euglycaemia. On advice from paediatric endocrinologist, the trial of long-acting insulin glargine was very successful and we were able to achieve normoglycaemia.

There are few reported cases [6],[7],[8] where long-acting insulin had been used for hyperglycaemia in ELBW babies. Stefano Passanisi et al.[7] reported that a term intrauterine growth restriction baby who developed hyperglycaemia at the age of 12 h. In this case, subcutaneous neutral protamine Hagedorn introduced as twice daily doses, but baby developed hypoglycaemia and after withdrawal became hyperglycaemic similar to our case. However, they shifted to the administration of insulin glargine, once every 24 h at the initial dose of 0.45 unit/kg/day subcutaneously into the buttock. The daily dose of insulin glargine was progressively lowered to 0.2 IU/kg/day. This regimen allowed a satisfactory blood glucose control.

In another case reported by Barone et al.,[6] where an ELBW baby (680 g) 28-week gestational age was treated with regular insulin initially as a continuous infusion but had same scenario of hypoglycaemia followed by hyperglycaemia after discontinuation of the insulin. Therefore, they transitioned to subcutaneous insulin glargine administered every 12 h (0.27 unit/kg/day) into the abdomen or buttocks. The daily insulin dose was lowered (0.1 units/dose) as a result of severe hypoglycaemia encountered with excellent response and achieving and maintaining persistent euglycaemia prompted discontinuation of insulin glargine. The patient displayed no further episodes of hyperglycaemia or hypoglycaemia and did not require further treatment.

Jeha et al.[8] reported three neonates who were successfully treated with glargine as well. Glargine, long-acting, basal insulin analogue, is manufactured by recombinant DNA expression in Saccharomyces cerevisiae, with the removal of an amino acid residue at position B30 and placement of a 14-carbon fatty acid attached to the amino acid residue at B29. The prolonged action of this insulin is the result of reversible binding of the fatty acid residue to serum albumin, which slows the release of active insulin monomers into systemic circulation following subcutaneous injection.[9] From a pharmacokinetic perspective, the duration of action of long-acting insulin is dose-dependent, ranging from 5.7 to 23.2 h, with onset of action at approximately 1–3 h and with peak effect occurring between 3 and 10 h post-administration. The pharmacokinetics of glargine has been evaluated in patients as young as 6 years of age and do not differ significantly when compared to pharmacokinetics in adolescents and adults [5] but no pharmacokinetic studies evaluated glargine in neonates.

Our findings and outcome were similar to the case report by Barone et al. where euglycaemia was achieved successfully by the use of glargine in ELBW baby, but our case is with the lowest weight (620 g) treated with glargine. It is suggested to perform studies evaluating the stability and pharmacokinetics of different dilutions of long-acting insulin in neonates to prepare recommendation to treat neonates and especially low-birth-weight babies with this regimen. Our experience in addition to other reported cases might guide the neonatologists to manage the cases of NDM using long-acting insulin products in neonates.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Aguilar-Bryan L, Bryan J. Neonatal diabetes mellitus. Endocr Rev 2008;29:265-91  Back to cited text no. 1
Kataria A, Palliyil Gopi R, Mally P, Shah B. Neonatal diabetes mellitus: Current perspective, Research and Reports in Neonatology, 2014;4:55-64.  Back to cited text no. 2
Neu A, Beyer P, et al. Diagnosis, Therapy and Control of Diabetes Mellitus in Children and Adolescents, German Diabetes Associaton: Clinical Practice Guidelines, Clin Endocrinol Diabetes 2014;122:425-34.  Back to cited text no. 3
Danne T, Lupke K, Walte K, et al. Insulin detemir is characterized by a consistent pharmacokinetic profile across age groups in children, adolescents, and adults with type 1 diabetes. Diabetes Care. 2003;26:3087-92.  Back to cited text no. 4
Yaffe SJ, Aranda JA. Pediatric Pharmacology: Therapeutic Principles in Practice (2/e) Philadelphia, PA: WB Saunders Co; 1992.  Back to cited text no. 5
Barone JV, Tillman EM, Ferry RJ. Treatment of transient neonatal diabetes mellitus with subcutaneous insulin glargine in an extremely low birth weight neonate. J Pediatr Pharmacol Ther 2011;16:291-7.  Back to cited text no. 6
Passanisi S, et al. Treatment of Transient Neonatal Diabetes Mellitus: Insulin Pump or Insulin Glargine? Our Experience, Diabetes Technol Ther 2014;16:880-4.  Back to cited text no. 7
Jeha GS, Venkatesh MP, Edelen RC, Kienstra KA, Karaviti L, Fernandes C. J. Neonatal diabetes mellitus: Patient reports and review of current knowledge and clinical practice. J Pediatr Endocrinol Metab 2005;18:1095-02.  Back to cited text no. 8
NovoNordisk. Levemir [package insert] NovoNordisk; 2009  Back to cited text no. 9


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