Ummu K. Jamaludin

Performance of STAR virtual trials for diabetic and non-diabetic in HTAA intensive care unit

Critically ill patients are commonly linked to stress-induced hyperglycaemia which relates to insulin resistance and the risk of per-diagnosed with diabetes and other metabolic illnesses. Thus, it is essential to choose the best practice of blood glucose management in order to reduce morbidity and mortality rates in intensive care unit. This study is focusing on clinical data of 210 critically ill patients in Hospital Tengku Ampuan Afzan (HTAA), Kuantan who underwent Intensive Insulin Therapy which utilized a sliding scale method. Patients were identified in two main groups of diabetic (123) and non-diabetic (87) where stochastic model is generated to observe 90% confidence interval of insulin sensitivity. Blood glucose levels comparison between these two cohorts is conducted to observe the percentage of blood glucose levels within targeted band of 4.4–10.0 mmol/L. It is found that 82% of BG levels are within tar gated band for non-diabetes cohort under stochastic targeted (STAR) glycaemic control protocol. However, only 59.6% and 70.6% BG levels are within targeted band for diabetes cohort for insulin infusion therapy used in HTAA and STAR protocols. Thus, further investigation on blood glucose control protocol for diabetes patients is required to increase the reliability and efficacy of current practice despite of patient safety.

Impact of haemodialysis on insulin sensitivity of acute renal failure (ARF) patients with sepsis in critical care

Critically ill patients often develop renal failure in addition to their primary diagnosis. However, the effect and impact of haemodialysis (HD) on insulin sensitivity in critically ill patients remains unclear. Specifically, this study investigates insulin sensitivity of acute renal failure (ARF) patients with sepsis who underwent HD and glycaemic control. Model-based insulin sensitivity (SI) profiles were identified for 20 critically ill ARF patients on Specialized Relative Insulin Nutrition Titration (SPRINT) glycaemic control during intervals onto HD (OFF/ON), and after HD (ON/OFF). Patients exhibited a median -18% (IQR -36% to -5% p<;0.05) reduction in measured SI after the OFF/ON dialysis transition, and a median 9% (IQR -5% to 37%, p<;0.05) rise after the ON/OFF transition. Almost 80% of patients exhibited decreased SI at the OFF/ON interval, and 60% exhibited increased SI at the ON/OFF transition. Results indicate that HD commencement has significant effect on insulin pharmacokinetics at a cohort and per-patient level. These results provide the data to design conclusive studies of HD effects on SI, and to inform glycaemic control protocol development and implementation for this specific group of critically ill patients with ARF-sepsis.

Levels and diagnostic value of model-based insulin sensitivity in sepsis: A preliminary study

Background and Aims: Currently, there is a lack of real-time metric with high sensitivity and specificity to diagnose sepsis. Insulin sensitivity (SI) may be determined in real-time using mathematical glucose-insulin models; however, its effectiveness as a diagnostic test of sepsis is unknown. Our aims were to determine the levels and diagnostic value of model-based SI for identification of sepsis in critically ill patients. Materials and Methods: In this retrospective, cohort study, we analyzed SI levels in septic (n = 18) and nonseptic (n = 20) patients at 1 (baseline), 4, 8, 12, 16, 20, and 24 h of their Intensive Care Unit admission. Patients with diabetes mellitus Type I or Type II were excluded from the study. The SI levels were derived by fitting the blood glucose levels, insulin infusion and glucose input rates into the Intensive Control of Insulin-Nutrition-Glucose model. Results: The median SI levels were significantly lower in the sepsis than in the nonsepsis at all follow-up time points. The areas under the receiver operating characteristic curve of the model-based SI at baseline for discriminating sepsis from nonsepsis was 0.814 (95% confidence interval, 0.675–0.953). The optimal cutoff point of the SI test was 1.573 × 10−4 L/mu/min. At this cutoff point, the sensitivity was 77.8%, specificity was 75%, positive predictive value was 73.7%, and negative predictive value was 78.9%. Conclusions: Model-based SI ruled in and ruled out sepsis with fairly high sensitivity and specificity in our critically ill nondiabetic patients. These findings can be used as a foundation for further, prospective investigation in this area.

Insulin sensitivity and sepsis score: A correlation between model-based metric and sepsis scoring system in critically ill patients

Sepsis is highly correlated with mortality and morbidity. Sepsis is a clinical condition demarcated as the existence of infection and systemic inflammatory response syndrome, SIRS. Confirmation of infection requires a blood culture test, which requires incubation, and thus results take at least 48 h for a syndrome that requires early direct treatment. Since sepsis has a strong inflammatory component, it is hypothesized that metabolic markers affected by inflammation, such as insulin sensitivity, might provide a metric for more rapid, real-time diagnosis. This study uses clinical data from 30 sepsis patients (7624 h in ICU) of whom 60% are male. Median age and median Apache II score are 63 years and 19, respectively. Model-identified insulin sensitivity (SI) profiles were obtained for each patient, and insulin sensitivity and its hourly changes were correlated with modified hourly sepsis scores (SSH1). SI profiles and values were similar across the cohort. The sepsis score is highly variable and changes rapidly. The modified hourly sepsis score, SSH1, shows a better relation with insulin sensitivity due to less fluctuation in the SIRS element. Median SI and median ΔSI of the cohort is 0.4193e-3 and 0.004253e-3 L/mU.min, respectively. Additionally, median SI are 4.392 × 10−4 L/mU min (SSH1 = 0), 4.153 × 10−4 L/mU min (SSH1 = 1), 3.752 × 10−4 L/mU min (SSH1 = 2) and 2.353 × 10−4 L/mU min (SSH1 = 3). Significant relationship between insulin sensitivity across different SSH1 groups was observed (p < 0.05) even when corrected for multiple comparisons. CDF of SI indicates that insulin sensitivity is more significant when comparing an hourly sepsis score at a very distinguished level.

Investigation of Glucose-Insulin Model Efficacy for Diabetes Patient in the ICU

This paper investigates the inter-relationship of blood glucose (BG) model fitting error percentage for both diabetic and non-diabetic patient’s status with ICING glucose-insulin model efficacy. Data were taken from 132 critically ill patients admitted in ICU of Hospital Tunku Ampuan Afzan (HTAA), Kuantan, Malaysia. The BG fitting error results are important to determine the efficacy and safety of chosen glucose-insulin model-based. Analysis results of per-patient and by-cohort were used to suggest whether diabetes is an influential factor for model BG fitting error efficacy. For diabetic per-patient and by-cohort, median model fit error are 0.29 and 0.31% respectively Meanwhile, for non-diabetic per-patient and by-cohort model fit error are 0.27 and 0.29% respectively. In conclusion, results demonstrated no significant difference between diabetic and non-diabetic patient in model fitting error. Thus, ICING model may be used to deliver real time model-based insulin therapy whether patient is diabetic or non-diabetic.

Blood glucose and sepsis score on sepsis patients requiring insulin therapy

Early treatment of sepsis is crucial in improving the patient condition and reduces mortality. The lack of information and methods to diagnose sepsis at an early stage is a significant barrier to early treatment. Treatment is normally based on clinical judgment since blood cultures are negative in the majority of sepsis or septic shock cases as reported in several studies. Even with blood cultures result, a delay in diagnosis may happen while waiting for the results. Therefore, clinical guidelines are still required to provide guidance for the clinician caring for a patient with severe sepsis or septic shock. In this study, a validated glucose-insulin model is used to capture patient-specific insulin sensitivity profile. The validated model is incorporated with a sepsis system to create a glucose-insulin model that describe sepsis occurrence. The relationship between insulin sensitivity, blood glucose and sepsis score is investigated using a retrospective data of 8 patients admitted in the Tengku Ampuan Afzan Hospital, Kuantan. Results indicate that there was a significant relationship between blood glucose level and sepsis score (p < 0.001), and insulin sensitivity with a sepsis score (p < 0.001). Additionally, blood glucose level was higher in a severe sepsis group compared to the non-sepsis group. Whereas, insulin sensitivity is lower in a severe sepsis group. Insulin sensitivity profile can be incorporated with the sepsis system for monitoring sepsis patients requiring insulin therapy as seen in this study. Thus, the sepsis glucose-insulin model can potentially be used as an indicator or tools for sepsis diagnosis.

Incretin effects and enteral feed transitions

Critically ill patients are regularly fed with constant enteral nutrition infusions. However, the incretin effects of its impact on endogenous insulin concentration and secretion remains to be investigated. Many studies concluded the incretin effects are strongly driven by enteral feeding. This chapter deliberates current scenario in intensive care unit dealing with hyperglycemia which can be assisted by glycemic control protocol to prevent mortality and other adverse occurrences. Brief discussions on methodology consideration including enteral nutrition criterion and the identification of insulin sensitivity were included. Analyses based on the findings of glycemic control protocol with enteral feed-driven incretin effects were also highlighted to allow investigation on the incretin effect in critically ill patients via the changes in insulin sensitivity between feeding transitions. Although results have made distinct the incretin effect successfully, there are still limitations to the current study such as isolated gastrointestinal hormones. Thus, this chapter aims to aid clinicians and researchers to integrate this physiological effect into their current practice and applications in treating critically ill patients with hyperglycemia and other conditions. It also provides platform to design conclusive studies on incretin effect and to inform glycemic control protocol development and implementation in critical care.

Observation of changes in model-based insulin sensitivity during haemodialysis transitions for critically ill patients

Abstract Most critically ill patients exhibit a myriad of symptoms with irregular glycaemic regulation and renal failure contributing to a large proportion of mortality and morbidity. Hence, the effect of dialysis on glycaemic regulation should be of interest to clinicians as it is a common therapy addressing renal failure. In this investigation, we measure transient changes in model-based insulin sensitivity during the commencement and end of dialysis periods in 51 critically ill patients with acute renal failure (ARF). The clinically validated model-based insulin sensitivity ( S I ) metric is a lumped parameter, which, in this case, can account for variance in insulin pharmacokinetics and production, as well as the efficiency of insulin mediated glucose uptake. Apparent S I is expected to be higher during renal failure as insulin will not be cleared as fast as the model assumed. Thus, it is hypothesized given model assumptions on steady, population levels of renal insulin clearance, that dialysis will cause a drop in model-based S I , and vice versa. This study is the first to investigate the effect of dialysis on insulin action of critically ill patients. This investigation found a significant reduction in model-based S I after the commencement of dialysis, but an insignificant change when dialysis was stopped. As dialysis was considered to have little effect on true insulin sensitivity and the effect on insulin production would have been contrary to the observed behavior, it was concluded that commencing dialysis had a significant effect in increasing insulin clearance over the cohort. This effect was not reciprocated immediately following dialysis due to a slower return to complete renal failure following treatment.

OP006 ENTERAL NUTRITION-ASSOCIATED INCRETIN EFFECT IN THE CRITICALLY ILL

Rationale: The effects of tight glycemic control (TGC) are beneficial in case of predominant use of parenteral nutrition (PN), but not when enteral nutrition (EN) is the predominant source of calories. This suggests the presence of an incretin effect, i.e. an increased release of endogenous insulin induced by EN. This effect would be supported if the amount of exogenous insulin required for glycemic control was increased during interruptions of EN, thereby reflecting improved insulin sensitivity (SI) due to the EN-related greater release of incretins.