The Relationship Between Corneal Nerve Density and Hemoglobin A1c in Patients With Prediabetes and Type 2 Diabetes

Diabetic polyneuropathy (DPN) and endothelial dysfunction are prevalent complications of diabetes mellitus. Currently, there are two non-invasive markers for endothelial dysfunction: flow-mediated dilation and reactive hyperaemia peripheral arterial tonometry (RH-PAT). However, the relationship between diabetic small fibre neuropathy and macroangiopathy remains obscure thus far. Corneal confocal microscopy (CCM) has emerged as a new diagnostic modality to assess DPN, especially of small fibre. To clarify the relationship between diabetic small fibre neuropathy and vascular dysfunction, we aimed to determine the functions of peripheral nerves and blood vessels through clinical tests such as nerve conduction study, coefficient of variation in the R-R interval, CCM, and RH-PAT in 82 patients with type 2 diabetes. Forty healthy control subjects were also included to study corneal nerve parameters. Correlational and multiple linear regression analyses were performed to determine the associations between neuropathy indices and markers for vascular functions. The results revealed that patients with type 2 diabetes had significantly lower values for most variables of CCM than healthy control subjects. RH-PAT solely remained as an explanatory variable significant in multiple regression analysis for several CCM parameters and vice versa. Other vascular markers had no significant multiple regression with any CCM parameters. In conclusion, endothelial dysfunction as revealed by impaired RH-PAT was significantly associated with CCM parameters in patients with type 2 diabetes. This association may indicate that small fibre neuropathy results from impaired endothelial dysfunction in type 2 diabetes. CCM parameters may be considered surrogate markers of autonomic nerve damage, which is related to diabetic endothelial dysfunction. This study is the first to report the relationship between corneal nerve parameter as small fibre neuropathy in patients with type 2 diabetes and RH-PAT as a marker of endothelial dysfunction.

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An Inconvenient Relationship of Hemoglobin A1c Level with Endothelial Function in Type 2 Diabetes

10.21203/rs.3.rs-23581/v1 ◽

2020 ◽

Author(s):

Takayuki Yamaji ◽

Takahiro Harada ◽

Yu Hashimoto ◽

Yuji Takaeko ◽

Masato Kajikawa ◽

...

Keyword(s):

Type 2 Diabetes ◽

Endothelial Dysfunction ◽

Endothelial Function ◽

Hba1c Level ◽

Hemoglobin A1c ◽

Antidiabetic Drugs ◽

Flow Mediated Vasodilation ◽

Relationship Of ◽

The Relationship

Abstract Background Diabetes is associated with endothelial dysfunction. However, there is little information on the relationship between hemoglobin A1c (HbA1c) level and endothelial function. This study evaluated the relationship between HbA1c level and flow-mediated vasodilation (FMD).Methods We measured FMD in 1215 patients with type 2 diabetes including 349 patients not taking antidiabetic drugs and 866 patients taking antidiabetic drugs. The patients were divided into four groups based on HbA1c levels: <48 mmol/mol, 48–52 mmol/mol, 53–63 mmol/mol, and ≥ 64 mmol/mol. (< 6.5%, 6.5–6.9%, 7.0-7.9%, ≥ 8.0%)Results An inverted U-shaped pattern of association between HbA1c level and FMD was observed at the peak of HbA1c of about 53 mmol/mol (7%). FMD was significantly smaller in the HbA1c < 48 mmol/mol (6.5%) group than in the HbA1c 48–52 mmol/mol (6.5–6.9%) group and HbA1c 53–63 mmol/mol (7.0-7.9%) group (p < 0.001 and p < 0.001), and FMD values were similar in the HbA1c < 48 mmol/mol (6.5%) group and HbA1c ≥ 64 mmol/mol (8.0%) group. There were no significant differences in nitroglycerine-induced vasodilation (NID) values among the four groups. After adjustments for confounding factors, FMD was significantly smaller in the HbA1c < 48 mmol/mol (6.5%) group than in the HbA1c 48–52 mmol/mol (6.5–6.9%) and HbA1c 53–63 mmol/mol (7.0-7.9%) group (p = 0.002 and p = 0.04). In patients not taking antidiabetic drugs, FMD was also significantly smaller in the HbA1c < 48 mmol/mol (6.5%) group than in the HbA1c 48–52 mmol/mol (6.5–6.9%) group and HbA1c 53–63 mmol/mol (7.0-7.9%) group (p < 0.001 and p = 0.02), and there were no significant differences in NID values among the four groups.Conclusions These findings suggest that a low HbA1c level of < 48 mmol/mol (6.5%) is associated with endothelial dysfunction. An HbA1c level of 48–52 mmol/mol (6.5–6.9%) may be appropriate for maintenance of endothelial function.

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