Relationship between insulin resistance and β-cell dysfunction in subphenotypes of prediabetes and type 2 diabetes.
BACKGROUND
There is little overlap between diabetes diagnosed by glycated hemoglobin (HbA1c) and blood glucose, and it is unclear which pathophysiological defects are captured when using HbA1c for diagnosis.


OBJECTIVE
We examined and compared the relationship between insulin sensitivity and β-cell function in different subphenotypes of prediabetes and type 2 diabetes (T2D).


METHODS
A cross-sectional analysis of the Danish ADDITION-PRO study was performed (n = 1713). Participants without known diabetes were classified into subgroups of prediabetes and T2D based on fasting or 2-hour glucose criteria or HbA1c. Insulin sensitivity and insulin release were determined from glucose and insulin concentrations during the oral glucose tolerance test, and disposition indices were calculated.


RESULTS
Individuals with prediabetes or T2D diagnosed by fasting glucose had lower absolute insulin release (P ≤ .01) and higher insulin sensitivity in response to glucose intake (P ≤ .01) but a similar disposition index (P ≥ .36), compared with individuals with elevated 2-hour glucose concentrations. Individuals with HbA1c-defined T2D or prediabetes had a mixture of the pathophysiological defects observed in the glucose-defined subgroups, and individuals with normoglycemia by HbA1c had worse pathophysiological abnormalities than individuals with normoglycemia by the glucose criteria.


CONCLUSIONS
On average, the diagnostic HbA1c criteria for diabetes and prediabetes identified individuals with a mixture of the pathophysiological characteristics found when using the glucose criteria, but the diversity and pathophysiology captured by the oral glucose tolerance test cannot be captured when applying the more simple HbA1c criteria. Whether the disease progression and prognosis will differ in individuals diagnosed by fasting glucose, 2-hour glucose, or HbA1c should be examined in longitudinal studies.
Steno Diabetes Center (K.F., N.B.J., M.E.J., D.V.), 2820 Gentofte, Denmark; Danish Diabetes Academy (N.B.J.), 5000 Odense, Denmark; Centre de Recherche Public de la Santé (D.R.W.), 1445 Strassen, Luxembourg; and Institute of Public Health (T.L.), Section of General Practice, University of Aarhus, 8000 Aarhus, Denmark.
Kristine
K
Færch
Nanna B
NB
Johansen
Daniel R
DR
Witte
Torsten
T
Lauritzen
Marit E
ME
Jørgensen
Dorte
D
Vistisen
D000368:Aged; D001786:Blood Glucose / Q000032:analysis; D015992:Body Mass Index; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000503:physiopathology*; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology*; D050417:Insulin-Secreting Cells / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D011236:Prediabetic State / Q000097:blood / Q000503:physiopathology*
D001786:Blood Glucose; D007328:Insulin