Key result
Hyperglycemia in T1D elevates oxidative stress, correlating with increased vascular stiffness and diabetic kidney disease.
Why the study?
The relationship between plasma oxidant and antioxidant levels in response to acute and chronic hyperglycemia and their association with vascular stiffness and diabetic kidney disease in type 1 diabetes is not fully understood.
Does acute and chronic hyperglycemia alter oxidant and antioxidant levels and associate with vascular stiffness and diabetic kidney disease in individuals with type 1 diabetes?
Observational (n=153)
Yes
Does acute and chronic hyperglycemia alter oxidant and antioxidant levels and associate with vascular stiffness and diabetic kidney disease in individuals with type 1 diabetes?
p-value: p=<0.01
Biomarkers of oxidative stress are elevated following acute and chronic hyperglycemia in type 1 diabetes and correlate with vascular stiffness and diabetic kidney disease severity.
Oxidative stress markers associate with stiffness and DKD in T1D; leaves open whether they add prognostic value beyond HbA1c or warrant targeted intervention.
BACKGROUND: Hyperglycemia-induced oxidative stress is a well-established pathological mediator of vascular complications in diabetes. We assessed plasma oxidant and antioxidant levels in response to acute and chronic hyperglycemia in relation to vascular stiffness and varying degrees of kidney disease in type 1 diabetes individuals. METHODS: The acute hyperglycemia study included 22 type 1 diabetic individuals with normal albumin excretion rate (AER) and 13 non-diabetic controls. These individuals received an acute glucose challenge during a 120-minute hyperglycemic clamp. The chronic hyperglycemia study included 118 type 1 diabetic individuals with chronically low (n = 60) or high (n = 58) HbA1c concentrations and varying degrees of diabetic kidney disease (DKD) classified as normal, moderate, or severe albuminuria (AER). Levels of malondialdehyde (MDA), reactive oxygen metabolites (ROMs), total antioxidant capacity (TAC), biological antioxidant potential (BAP) and superoxide dismutase (SOD) were measured from plasma or serum samples in the FinnDiane study. RESULTS: Levels of MDA (p < 0.01) and ROMs (p < 0.01) were elevated in type 1 diabetes individuals compared to non-diabetic controls at baseline. Acute hyperglycemia further increased MDA levels (p < 0.05) and sustained the elevation of ROMs in type 1 diabetes individuals. Acute hyperglycemic challenge impaired TAC in both non-diabetic (p < 0.05) and type 1 diabetes (p < 0.01) individuals compared to baseline whereas BAP was increased (p < 0.05) with no difference observed in non-diabetic controls. There was a positive association between high circulating MDA and AIx (r2 = 0.611, p = 0.05), and between delta ROMs and delta AIx (r2 = 0.955, p = 0.014) in combined analysis of individuals with type 1 diabetes and non-diabetic controls. Type 1 diabetes individuals with varying status of DKD, showed elevated levels of ROMs in those with high HbA1c compared to their counterpart with low HbA1c (p < 0.05). Individuals with severe albuminuria showed elevated ROM levels (p < 0.01) and depressed antioxidant capacity (p < 0.01) compared to those with normal AER of comparable HbA1c concentrations. CONCLUSIONS: Biomarkers of oxidative stress are associated with vascular stiffness and DKD following acute and chronic hyperglycemic exposure and may provide added value to HbA1c in understanding disease pathology, predicting risk and assessing the status of secondary complications of type 1 diabetes.
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Adeshara et al. (2024) conducted an observational in Type 1 diabetes (n=153). Acute and chronic hyperglycemia vs. Non-diabetic controls and low HbA1c was evaluated on Plasma oxidant (MDA, ROMs) and antioxidant (TAC, BAP) levels (p=<0.01). Acute and chronic hyperglycemia in type 1 diabetes significantly elevated oxidative stress markers (MDA and ROMs, p < 0.01), which positively correlated with increased vascular stiffness and diabetic kidney disease severity.
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