Contributions of basal and postprandial hyperglycemia over a wide range of A1C levels before and after treatment intensification in type 2 diabetes.
OBJECTIVE
To determine the relative contributions of basal hyperglycemia (BHG) versus postprandial hyperglycemia (PPHG) before and after treatment intensification in patients with glycated hemoglobin A(1c) (A1C) >7.0% while on prior oral therapy.


METHODS
Self-measured, plasma-referenced glucose profiles and A1C values were evaluated from participants in six studies comparing systematically titrated insulin glargine with an alternative regimen (adding basal, premixed, or prandial insulin, or increasing oral agents). Hyperglycemic exposure (>100 mg/dL [5.6 mmol/L]) as a result of BHG versus PPHG was calculated.


RESULTS
On prior oral therapy, 1,699 participants (mean age 59 years, diabetes duration 9 years) had mean fasting plasma glucose (FPG) of 194 mg/dL (10.8 mmol/L), and mean A1C was 8.7%. BHG contributed an average of 76-80% to hyperglycemia over the observed range of baseline A1C levels. Adding basal insulin for 24 or 28 weeks lowered mean FPG to 117 mg/dL (6.5 mmol/L), A1C to 7.0%, and BHG contribution to 32-41%. Alternative regimens reduced FPG to 146 mg/dL (8.1 mmol/L), A1C to 7.1%, and the contribution of BHG to 64-71%. BHG contributions for patients with A1C averaging 7.6-7.7% were 76% at baseline and 34 and 68% after adding basal insulin or other therapies, respectively.


CONCLUSIONS
When A1C is >7.0% despite oral therapy, BHG routinely dominates exposure. Intensified therapy reduces A1C and changes this relationship, but BHG amenable to further intervention still accounts for one-third of total hyperglycemia after basal insulin treatment and two-thirds after alternative methods.
Department of Medicine, Division of Endocrinology, Diabetes & Clinical Nutrition, Oregon Health and Science University, Portland, Oregon, USA. riddle@ohsu.edu
Matthew
M
Riddle
Guillermo
G
Umpierrez
Andres
A
DiGenio
Rong
R
Zhou
Julio
J
Rosenstock
D001786:Blood Glucose / Q000187:drug effects*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism*; D006801:Humans; D006943:Hyperglycemia / Q000188:drug therapy*; D000069036:Insulin Glargine; D007336:Insulin, Isophane / Q000008:administration & dosage; D049528:Insulin, Long-Acting / Q000008:administration & dosage*; D061386:Insulin, Regular, Human / Q000008:administration & dosage; D000068880:Isophane Insulin, Human; D008297:Male; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
D001786:Blood Glucose; D006442:Glycated Hemoglobin; D000069036:Insulin Glargine; D007336:Insulin, Isophane; D049528:Insulin, Long-Acting; D061386:Insulin, Regular, Human; D000068880:Isophane Insulin, Human