Elsevier

Early Human Development

Volume 91, Issue 11, November 2015, Pages 655-659
Early Human Development

The potential risks and benefits of insulin treatment in hyperglycaemic preterm neonates

https://doi.org/10.1016/j.earlhumdev.2015.08.011Get rights and content

Abstract

Preterm hyperglycaemia in the first 2 weeks of life is common under 29 weeks gestation and is associated with increased mortality and morbidity. While the definition of hyperglycaemia is reasonably consistent (> 8 mmol/L) the treatment threshold varies widely in clinical practice. Insulin therapy is the most common approach despite international guidance urging caution because of hypoglycaemia. Significant hypoglycaemia is unusual outside studies targeting normoglycaemia. Insulin treatment also forms part of a nutritional strategy aiming to optimise early protein and energy intake so minimising the risk of preterm postnatal growth failure. Early parenteral amino acids also improve blood glucose control. There is some evidence of improved postnatal head growth with this approach but longer term neurodevelopmental studies are required. Glucose reduction is the alternative approach. This compromises early nutritional intake but avoids the potential for long-term cardiovascular and metabolic complications linked with high postnatal nutritional intakes and theoretically, insulin treatment.

Section snippets

Mechanisms of preterm hyperglycaemia

The mechanism of hyperglycaemia in preterm infants is not fully understood but it may relate to both relative insulin resistance and defective islet β-cell function [6]. The former is suggested by:

  • 1.

    Higher postnatal blood glucose and insulin levels compared to term equivalent [1]

  • 2.

    Failure to suppress glucose production despite hyperglycaemia (increased hepatic insulin resistance) [6]

  • 3.

    Less abundant insulin-sensitive tissue (increased peripheral insulin resistance)

  • 4.

    Hepatic and peripheral insulin

Definition and incidence of hyperglycaemia

There is a reasonably consistent definition of neonatal hyperglycaemia in the literature: 6.9–8.3 mmol/l [18]. In a study of infants < 1500 g, 80% of infants had evidence of glucose levels > 8 mmol/L in the first week of life [19]. However, the treatment threshold varies widely between neonatal services with nearly all UK tertiary neonatal intensive care units using blood glucose levels between 8 and 14 mmol/L (Fig. 1a) [20].The majority choose > 12 mmol/l in 2 consecutive blood glucose measurements < 4 

Use of insulin in current clinical practice

A number of small observational studies have shown that insulin is an effect way to treat hyperglycaemia in the preterm infants. The American Academy of Paediatrics has supported the use of insulin for 30 years and many international nutrition surveys confirm widespread use of insulin [20], [21], [22]. UK surveys indicate one third of level 3 NICUs avoid insulin use (Fig. 1b), by limiting early glucose intakes and/or reducing glucose intake in the event of hyperglycaemia [20], [21]. Glucose

Benefits

There is clear evidence [27] from multiple observational studies and one small RCT [28] that insulin infusions can effectively treat hyperglycaemia in VPI. No differences in mortality or morbidity have been identified although no study has been adequately powered to investigate these outcomes [27]. More recently, the focus has been on comparing differing insulin regimens and the potential benefits of achieving consistent normoglycaemia. Similar approaches in adult intensive care initially

Glucose reduction

Glucose reduction is an effective treatment for preterm hyperglycaemia [27]. There is only one small RCT comparing this approach with insulin infusion [48]. Glucose reduction is theoretically less likely to cause hypoglycaemia although this has yet to be proven in a clinical trial. The main risk is inadequate early energy intake and growth failure. Lower energy intakes in the first week of life are associated with poorer neurodevelopmental outcome [49]. Given the limits imposed by the risk and

Implications for clinical practice

Variations in current clinical practice clearly reflect the state of equipoise that follows from the limited evidence base. The use of insulin therapy allows the potential benefits of a high nutrient intake strategy (including insulin therapy) for head growth and neurodevelopment and may have direct benefits for growth and development. However, concerns remain about the risk of hypoglycaemia and neurological sequelae leading many clinicians to opt for glucose reduction as the combined or sole

Future research

  • 1.

    An RCT comparing insulin therapy (with maximum parenteral protein and energy intake) and glucose reduction (with modified protein and energy intake) for hyperglycaemia in VPI and powered to investigate long-term neurocognitive outcomes is required.

  • 2.

    Physiological studies exploring the interaction between AA (both total and individual), exogenous insulin administration, and insulin-IGF-I growth axis are needed.

  • 3.

    Studies are required to evaluate better glucose monitoring and insulin dosage regimens

Conflict of interest

The author has no competing interests to declare.

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