Bruhn Lea, Vistisen Dorte, Vainø Camilla Trine Ravn, Perreault Leigh, Færch Kristine
Steno Diabetes Center Copenhagen, Gentofte, Denmark.
University of Colorado Denver, Denver, CO, USA.
Endocrine. 2020 May;68(2):306-311. doi: 10.1007/s12020-020-02234-3. Epub 2020 Feb 28.
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.
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.
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.
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.
对于正常及糖尿病前期范围内血红蛋白A1c（HbA）的潜在生理机制知之甚少。我们确定了空腹血糖（FPG）、餐后2小时血糖（2hPG）、胰岛素分泌、胰岛素敏感性和内源性葡萄糖生成对正常及糖尿病前期范围内HbA水平的影响。
共研究了62名丹麦葡萄糖调节正常或受损的男性和女性。测量HbA水平，并让参与者进行口服葡萄糖耐量试验以测量FPG和2hPG，进行静脉葡萄糖耐量试验以测定第一相胰岛素释放，并进行高胰岛素正常血糖钳夹试验以评估外周和肝脏胰岛素敏感性。通过线性回归分析分析HbA与不同葡萄糖代谢指标之间的关联。
研究人群的HbA水平范围为28至45 mmol/mol（4.7-6.3%）。FPG浓度每升高1个标准差（对数）（约1 mmol/L），HbA浓度升高2 mmol/mol（P < 0.001）。相比之下，第一相胰岛素分泌或处置指数每升高1个标准差（对数），HbA水平降低1.5 mmol/mol（P < 0.05）。HbA与外周或肝脏胰岛素敏感性、内源性葡萄糖生成或2hPG水平无关。
正常及糖尿病前期范围内的HbA水平似乎在更大程度上反映了胰岛素分泌减少而非胰岛素抵抗。因此，通过HbA识别高危个体的早期预防策略并不简单。需要更多关于如何直接或间接改善高危个体β细胞健康的研究。
