Physiological factors contributing to HbA in the normal and pre-diabetic range: a cross-sectional analysis.

PURPOSE

Little is known about the underlying physiology that contributes to Haemoglobin A1c (HbA) in the normal and pre-diabetic range. We determined the contribution of fasting plasma glucose (FPG), 2-h plasma glucose (2hPG), insulin secretion, insulin sensitivity and endogenous glucose production to HbA levels in the normal and pre-diabetic range.

METHODS

A total of 62 Danish men and women with normal or impaired glucose regulation were studied. HbA levels were measured and participants underwent an oral glucose tolerance test with measurements of FPG and 2hPG, an intravenous glucose tolerance test for determination of first-phase insulin release, and a hyperinsulinaemic euglycaemic clamp for estimation of peripheral and hepatic insulin sensitivity. Associations of HbA with the different measures of glucose metabolism were analysed by linear regression analysis.

RESULTS

HbA levels ranged from 28 to 45 mmol/mol (4.7-6.3%) in the study population. 1 SD higher (log) FPG concentration (~1 mmol/L) was associated with 2 mmol/mol higher HbA concentration (P < 0.001). In comparison, 1 SD higher levels of (log) first-phase insulin secretion or (log) disposition index were associated with 1.5 mmol/mol lower HbA levels (P < 0.05). HbA was not associated with peripheral or hepatic insulin sensitivity, endogenous glucose production or 2hPG levels.

CONCLUSION

HbA levels within the normal and pre-diabetic range seem to reflect decreased insulin secretion to a higher extent than insulin resistance. Therefore, early prevention strategies for high-risk individuals identified by HbA are not straightforward. More research on how to improve the health of beta cells either directly or indirectly in high-risk individuals is needed.