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Physiological factors contributing to HbA1c in the normal and pre-diabetic range: a cross-sectional analysis

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@article{ab4eba86cc084c87ba574f0c872b73eb,
title = "Physiological factors contributing to HbA1c in the normal and pre-diabetic range: a cross-sectional analysis",
abstract = "Purpose: Little is known about the underlying physiology that contributes to Haemoglobin A1c (HbA 1c) 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 1c 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 1c 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 1c with the different measures of glucose metabolism were analysed by linear regression analysis. Results: HbA 1c 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 1c 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 1c levels (P < 0.05). HbA 1c was not associated with peripheral or hepatic insulin sensitivity, endogenous glucose production or 2hPG levels. Conclusion: HbA 1c 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 1c are not straightforward. More research on how to improve the health of beta cells either directly or indirectly in high-risk individuals is needed. ",
keywords = "2-h plasma glucose (2hPG), Fasting plasma glucose (FPG), Haemoglobin A1c (HbA ), Insulin secretion, Insulin sensitivity, Pre-diabetes",
author = "Lea Bruhn and Dorte Vistisen and Vain{\o}, {Camilla Trine Ravn} and Leigh Perreault and Kristine F{\ae}rch",
year = "2020",
month = may,
day = "1",
doi = "10.1007/s12020-020-02234-3",
language = "English",
volume = "68",
pages = "306--311",
journal = "Endocrine",
issn = "1355-008X",
publisher = "Humana Press, Inc",
number = "2",

}

RIS

TY - JOUR

T1 - Physiological factors contributing to HbA1c in the normal and pre-diabetic range

T2 - a cross-sectional analysis

AU - Bruhn, Lea

AU - Vistisen, Dorte

AU - Vainø, Camilla Trine Ravn

AU - Perreault, Leigh

AU - Færch, Kristine

PY - 2020/5/1

Y1 - 2020/5/1

N2 - Purpose: Little is known about the underlying physiology that contributes to Haemoglobin A1c (HbA 1c) 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 1c 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 1c 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 1c with the different measures of glucose metabolism were analysed by linear regression analysis. Results: HbA 1c 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 1c 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 1c levels (P < 0.05). HbA 1c was not associated with peripheral or hepatic insulin sensitivity, endogenous glucose production or 2hPG levels. Conclusion: HbA 1c 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 1c are not straightforward. More research on how to improve the health of beta cells either directly or indirectly in high-risk individuals is needed.

AB - Purpose: Little is known about the underlying physiology that contributes to Haemoglobin A1c (HbA 1c) 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 1c 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 1c 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 1c with the different measures of glucose metabolism were analysed by linear regression analysis. Results: HbA 1c 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 1c 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 1c levels (P < 0.05). HbA 1c was not associated with peripheral or hepatic insulin sensitivity, endogenous glucose production or 2hPG levels. Conclusion: HbA 1c 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 1c are not straightforward. More research on how to improve the health of beta cells either directly or indirectly in high-risk individuals is needed.

KW - 2-h plasma glucose (2hPG)

KW - Fasting plasma glucose (FPG)

KW - Haemoglobin A1c (HbA )

KW - Insulin secretion

KW - Insulin sensitivity

KW - Pre-diabetes

UR - http://www.scopus.com/inward/record.url?scp=85081358629&partnerID=8YFLogxK

U2 - 10.1007/s12020-020-02234-3

DO - 10.1007/s12020-020-02234-3

M3 - Journal article

C2 - 32112239

VL - 68

SP - 306

EP - 311

JO - Endocrine

JF - Endocrine

SN - 1355-008X

IS - 2

ER -

ID: 59467005