Management of critically ill patients with type 2 diabetes: The need for personalised therapy

Table 8 Observational and interventional studies and outcomes related to glycaemic variability (chronological order)

Ref.	Year	Study pts	Study point	Non diabetic patients	Diabetic patients	Overall message
Egi et al[65]	2006	7049	GV (measured by SD and %CV) vs mortality (hospital and ICU)	Both mean and GV of blood glucose were significantly and independently associated with ICU and hospital mortalityGV was a stronger predictor of ICU mortality than mean glucose concentration	Inc mortality when comparing highest and lowest glucose SDNo other significant relation with blood glucose (SD and mean) and ICU/hospital mortality Logistic regression: DM associated with decrease OR for ICU mortality	The mean ± SD of blood glucose: Survivors 1.7 ± 1.3 mmol/L vs Non survivors 2.3 ± 1.6 mmol/L (P < 0.001)Post logistic regression analysis, both mean and SD of blood glucose were significantly associated with ICU and hospital
Ali et al[66]	2008	1246	GV vs hospital mortality in septic ICU patients	GV is independently associated with hospital mortality in sepsis	Mortality rise remained even after adjusting for a diagnosis of diabetes	Higher observed mortality with increasing levels of variabilityHigher odds of hospital mortality with lower mean blood glucose + high GV or higher mean blood glucose + lower GV
Krinsely[67]	2008	3252	GV vs mortality in ICU patients	Inc GV conferred a strong independent risk of mortality	Multivariable regression analysis demonstrated that diabetes had an independent positive correlation to SD	Amount of GV had a significant effect on mortality - e.g., patients with mean blood glucose 3.9-5.5 mmol/L mortality: Lowest GV 6% while high GV 30%
Krinsely[68]	2009	4084	Impact of DM or its absence on GV as a risk factor for mortality	Low GV was associated with increased survivalHigh GV was associated with increased mortality	Higher measures of GVNo association between GV and mortality among diabetics	Attempts to minimize GV may have a significant beneficial impact on outcomes of critically ill patients without diabetes
Lundelin et al[69]	2010	42	Glycemic dynamics (measured via non-lineal dynamics) vs mortality in ICU patients	Loss of complexity (therefore higher variability) in glycaemia time series is associated with higher mortality	This association persisted in diabeticsNo difference in DFA (detrended fluctuation analysis a measure of complexity) between DM and nondiabetics	In critically ill patients, there is a difference in the complexity of the glycaemic profile between survivors and nonsurvivorsLoss of complexity correlates with higher mortality
1Meyfroidt et al[71]	2010	2 748	Blood glucose signal characteristics vs hospital mortality,	GV was independently associated with hospital mortality	Increased mortality was seen in both diabetics and non diabetic patients.	Increased glucose amplitude variation was associated with mortality, irrespective of blood glucose level
Hoang et al[44]	2014	299	Prevalance of unrecognized DM amongst those with CIAH and the association between baseline glycaemia and mortality	102 (34%) had no history of DM14/102 (14%) had unrecognized DM (diagnosed with HbA1c ≥ 6.5)	197 (66%) had a history of DM	Lower HbA1c had inc mortality (in this population of CIAH patients) despite lower median glucose values and less glucose variabilityMortality in HbA1c < 6.5 (19%) vs HbA1c ≥ 6.5 (12%), P = 0.04
Donati et al[70]	2014	2 782	GV and mean BGLs vs mortality and intensive care unit-acquired infections	High GV is associated with higher risk of ICU acquired infection and mortality	Diabetic patients had higher mean BGL and GVNo change in mortality or infections	Mean BGL was not associated with infections and mortality

¹Interventional study data - pooled from the Leuven trials. GV: Glycaemic variability; SD: Standard deviation; %CV: Coefficient of variation; Inc: Increased; Dec: Decreased; OR: Odds rat.