The major finding of this study is that compared to patients with T2D and control subjects, the levels of IMA were significantly elevated in patients with T2DK. Diabetic ketosis was the significant factor influencing serum IMA levels in the participants. Insulin treatment had a favorable effect on glycemic control, IMA and CRP levels. IMA was a risk marker for T2DK and more sensitive than CRP in distinguishing T2DK.
In recent years, researchers have focused their attention on the pathological role of chronic inflammatory and free radicals in T2D. Existing data that show that before the complications of diabetes become clinically evident, hyperglycemia-induced oxidative stress occurs.18
IMA was a biochemical evaluation based on serum albumin binding to cobalt. IMA is not tissue specific and is elevated in subjects who undergo oxidative stress other than cardiac ischemia. There are concerns about tissue-specificity of IMA, as it has been suggested that IMA is a biomarker for other oxidative stress or ischemia-related diseases.19
The possible role of IMA was confirmed in previous studies.4,6,10–12
In the present study, the T2DK patients had significantly poorer glycemic control, which was associated with an increase in inflammatory and oxidative stress biomarkers. Higher levels of IMA and CRP were detected in patients with T2D and T2DK. Hyperglycemia and inflammation reduces the capacity of albumin to bind cobalt, resulting in higher IMA levels.20
Based on the above data, the IMA is a relatively new biomarker that may be a valuable signal for oxidative stress in patients with T2DK.
Increased levels of oxidative stress, pro-inflammatory markers, and downstream effector adhesion molecules occur in patients with T2D.16,21,22
T2D is intimately linked to hypertriglyceridaemia. The level of CRP is increased in diabetic patients with severe DKA, even in the absence of an infection, and may serve as a marker for systemic inflammatory response syndrome.23
Diabetic ketonuria is common among newly diagnosed or untreated patients with T2D and has been used to predict pathologic features or metabolic acidosis.14
Among Japanese patients with acute onset diabetic ketosis, there was a preponderance of males.24
The present study obtained similar results: T2DK was poorly controlled and male in the majority. An increase in serum IMA was associated with hyperketonemia in patients. However, there was no correlation between the IMA and CRP. CRP is regulated by the pro-inflammatory cytokines IL-6, IL-1β, and TNF-α.15
The mechanisms of CRP and IMA production are apparently different. The results of the ROC analysis revealed that IMA could reflect T2DK and was superior to CRP. In contrast, plasma CRP levels were not sensitive or specific enough to reflect T2DK. In agreement with the present study, the IMA could be a risk biomarker for T2DK. The sensitivity and specificity of the IMA depend on the clinical characteristics of the patients under investigation. The contributing factors and associations are being elucidated but remain unclear in T2DK states. Further studies are required to investigate the role of IMA in diabetic crises.
Diabetic ketoacidosis and nonketotic hyperglycemia are two acute hyperglycemic emergencies. The plasma levels of pro-inflammatory cytokines, markers of oxidative stress, and lipid peroxidation are elevated on admission in patients with hyperglycemic crises.25
The elevated levels of ketone body acetoacetate can generate oxygen radicals and cause lipid peroxidation in endothelial cells.26
In diabetic ketotic patients, the serum IMA and CRP concentrations were high at the beginning of hospitalization. T2D patients with ketonuria were more likely to be treated with insulin than those without ketonuria. In this study, the CRP and IMA levels were reduced in the T2DK patients, and control over plasma glucose was improved. T2D eventually leads to absolute or relative insulin deficiency. T2DK is the cause of pancreatic β-cells aggravation. As evident by a reduction in CRP, during T2D, insulin may have a modest anti-inflammatory effect. Insulin suppresses pro-inflammatory cytokines, not only by preventing hyperglycemia but also by modulating key inflammatory molecules.27
In summary, the markers CRP and IMA are higher in patients with T2DK but decreased following the treatments. Increasing levels of IMA were independently and significantly associated with T2DK. The present results suggest that IMA may be an interesting biomarker for predicting T2DK. The status of the proinflammatory cytokines and markers of oxidative stress in hyperglycemic crises of diabetic ketosis should be explored.