Glycaemic control on nutritional support: finding stability in unstable times
Authors: Pieter Gillard, Sara Charleer, Chantal Mathieu
Journal: The Lancet Diabetes & Endocrinology (2019)

Achieving good glycaemic control in hospital inpatients is a challenge for physicians and nursing teams.1Ng LS Curley MAQ “One more thing to think about…” Cognitive burden experienced by intensive care unit nurses when implementing a tight glucose control protocol.J Diabetes Sci Technol. 2012; 6: 58-64Crossref PubMed Scopus (10) Google Scholar Time spent in hyperglycaemia, episodes of hypoglycaemia, and glycaemic variability contribute to increased morbidity, mortality, length of hospital stay, and costs.2Moghissi ES Korytkowski MT DiNardo M et al.American Association of Clinical Endocrinologists and American Diabetes Association consensus statement on inpatient glycemic control.Diabetes Care. 2009; 32: 1119-1131Crossref PubMed Scopus (924) Google Scholar, 3Finfer S Liu B Chittock DR et al.Hypoglycemia and risk of death in critically ill patients.N Engl J Med. 2012; 367: 1108-1118Crossref PubMed Scopus (686) Google Scholar, 4Mendez CE Mok K-T Ata A Tanenberg RJ Calles-Escandon J Umpierrez GE Increased glycemic variability is independently associated with length of stay and mortality in noncritically ill hospitalized patients.Diabetes Care. 2013; 36: 4091-4097Crossref PubMed Scopus (134) Google Scholar The difficulty associated with achieving good inpatient glycaemic control is driven by the complexity of clinical conditions associated with high or low glucose. Patients requiring insulin therapy are admitted to different departments throughout the hospital because of the existence of diverse pathologies, and they are often not under the care of a specialist diabetes team, contributing to glycaemic instability. Other factors contributing to this complexity are associated comorbidities, such as inflammation, fever, sepsis, and pain, as well as varying amounts of food intake, and intake of steroids. The background of pre-existing diabetes also differs substantially among hospital inpatients, with patients using a wide variety of antidiabetes therapies before being admitted to hospital. Furthermore, enteral and parenteral nutrition are well known causes of hyperglycaemia in people with and without pre-existing diabetes.5Davidson P Kwiatkowski CA Wien M Management of hyperglycemia and enteral nutrition in the hospitalized patient.Nutr Clin Pract. 2015; 30: 652-659Crossref PubMed Scopus (33) Google Scholar, 6Pasquel FJ Spiegelman R McCauley M et al.Hyperglycemia during total parenteral nutrition: an important marker of poor outcome and mortality in hospitalized patients.Diabetes Care. 2010; 33: 739-741Crossref PubMed Scopus (106) Google Scholar Patients receive enteral and parenteral nutrition in variable ways, ranging from continuous treatment to intermittent or bolus infusion, sometimes in combination with unpredictable and variable oral intake or intravenous glucose administration. Patients presenting with hyperglycaemia are typically given intravenous, subcutaneous, or oral antidiabetes therapy while in hospital. Existing guidelines emphasise the importance of good glycaemic control for inpatients, but for patients on nutritional support this usually involves complex insulin regimens.7American Diabetes AssociationDiabetes care in the hospital: standards of medical care in diabetes.Diabetes Care. 2019; 42: S173-S181Crossref PubMed Scopus (155) Google Scholar Intravenous insulin delivery is an efficient way to keep glycaemia within acceptable ranges; however, it places a substantial burden on workload and resources and is not usually allowed outside the critical care setting. Many services, therefore, prefer subcutaneous insulin therapy over the burden of intravenous insulin delivery. In The Lancet Diabetes & Endocrinology, Charlotte Boughton and colleagues8Boughton CK Bally L Martignoni F et al.Fully closed-loop insulin delivery in inpatients receiving nutritional support: a two-centre, open-label, randomised controlled trial.Lancet Diabetes Endocrinol. 2019; (published online March 29.)http://dx.doi.org/10.1016/S2213-8587(19)30061-0Summary Full Text Full Text PDF PubMed Scopus (43) Google Scholar report the results of a randomised controlled trial comparing subcutaneous insulin administration via a fully closed-loop system with conventional subcutaneous insulin therapy in accordance with local clinical practice in two centres (in the UK and Switzerland). They showed that, in patients on enteral or parenteral nutrition (or both), an investigational closed-loop system provides superior glycaemic control to conventional therapy. Few studies have been published on the use of a closed-loop delivery system in non-critical care settings. Previous evidence for the efficacy of closed-loop insulin delivery on general wards comes from the same group, in patients with type 2 diabetes.9Bally L Thabit H Hartnell S et al.Closed-loop insulin delivery for glycemic control in noncritical care.N Engl J Med. 2018; 379: 547-556Crossref PubMed Scopus (111) Google Scholar, 10Thabit H Hartnell S Allen JM et al.Closed-loop insulin delivery in inpatients with type 2 diabetes: a randomised, parallel-group trial.Lancet Diabetes Endocrinol. 2017; 5: 117-124Summary Full Text Full Text PDF PubMed Scopus (72) Google Scholar This study8Boughton CK Bally L Martignoni F et al.Fully closed-loop insulin delivery in inpatients receiving nutritional support: a two-centre, open-label, randomised controlled trial.Lancet Diabetes Endocrinol. 2019; (published online March 29.)http://dx.doi.org/10.1016/S2213-8587(19)30061-0Summary Full Text Full Text PDF PubMed Scopus (43) Google Scholar adds to the existing evidence and supports the use of closed-loop systems in inpatients on enteral or parental feeding (or both), whose glycaemia is difficult to control. A possible limitation of Boughton and colleagues' analysis8Boughton CK Bally L Martignoni F et al.Fully closed-loop insulin delivery in inpatients receiving nutritional support: a two-centre, open-label, randomised controlled trial.Lancet Diabetes Endocrinol. 2019; (published online March 29.)http://dx.doi.org/10.1016/S2213-8587(19)30061-0Summary Full Text Full Text PDF PubMed Scopus (43) Google Scholar is that the closed-loop protocol is detailed, but conventional subcutaneous insulin therapy was pragmatic and done in accordance with local clinical practice. Although absence of a clear protocol for conventional therapy is often the reality due to the variability in patients and circumstances, a standardised protocol with clear glycaemic targets, a minimal number of glucose measurements, and type and timing of insulin adjusted to feeding regimens could have resulted in similar outcomes to those achieved with the closed-loop system. Closed-loop systems have the potential to reduce workload because of automation of both insulin delivery and glucose measurements, but might also increase the burden on diabetes teams; for example, technical issues or defects might occur, and back-up protocols will need to be activated to avoid unsafe dysregulation of glycaemic control. In a quarter of patients, the study was suspended temporarily because of transfer to intensive care, surgery, or other procedures (eg, radiology). In these cases, back-up protocols should be in place, which might lead to an increase in workload. Therefore, future studies should report on workload and costs, including the initial and continued training needed for teams not specialised in diabetes on general wards, the additional work required for diabetes or endocrinology teams, costs related to the safe reuse of parts of the closed-loop system, and costs of and work needed for integration of these systems into electronic medical records.11Wang M Singh LG Spanakis EK Advancing the use of CGM devices in a non-ICU setting.J Diabetes Sci Technol. 2019; (published online Jan 13.)DOI:10.1177/1932296818821094Crossref Scopus (19) Google Scholar Another point of concern in this trial8Boughton CK Bally L Martignoni F et al.Fully closed-loop insulin delivery in inpatients receiving nutritional support: a two-centre, open-label, randomised controlled trial.Lancet Diabetes Endocrinol. 2019; (published online March 29.)http://dx.doi.org/10.1016/S2213-8587(19)30061-0Summary Full Text Full Text PDF PubMed Scopus (43) Google Scholar is that almost a quarter of patients discontinued the closed-loop system because of discomfort when wearing the device, indicating that future work should focus on the acceptability of wearing these kinds of multifaceted devices and in motivating patients to do the necessary handling, such as finger-sticking, correctly. The positive feedback of participants at the end of the study indicates that closed-loop systems were received positively by most patients. Improvements in wearability, elimination of interference with drugs commonly used in hospital (eg, paracetamol or heparin), and reductions in the need for calibrations (as has been achieved with some more recently introduced glucose sensors) might further improve acceptability. Finally, the use of closed-loop systems might help in the study of optimal glycaemic targets in patients in both critical and non-critical care settings. These studies have not been done partly because of difficulties in designing and executing such complex trials. Closed-loop systems should be able to keep glucose concentrations within tight preset ranges while decreasing adverse events linked to severe hypoglycaemia and hyperglycaemia. If future studies show improvement in patient morbidity and mortality, and savings in workload and costs (ie, by reducing length of hospital stay), in addition to improvements in glycaemic control, then the use of closed-loop insulin delivery in inpatients will be a step closer to reality. But first, investigational closed-loop systems should be approved by regulatory authorities to become commercially available, even in the less complex outpatient setting. PG reports personal fees from Novo Nordisk, Janssen Pharmaceuticals, Boehringer Ingelheim, Medtronic, Bayer, and Abbott, and non-financial support for travel from Sanofi, Menarini, and Roche. SC reports non-financial support for travel from Medtronic and Roche Diabetes Care. CM reports research grants and personal fees from Novo Nordisk, Sanofi, Merck Sharp & Dohme, Eli Lilly, Novartis, Boehringer Ingelheim, Roche Diagnostics, Medtronic, Intrexon, and Abbott, and personal fees from ActoBio Therapeutics, AstraZeneca, Pfizer, Hanmi Pharmaceuticals, UCB, and Dianax. Fully closed-loop insulin delivery in inpatients receiving nutritional support: a two-centre, open-label, randomised controlled trialClosed-loop insulin delivery is an effective treatment option to improve glycaemic control in patients receiving nutritional support in hospital. Full-Text PDF Open Access