TY - JOUR
T1 - Paradigm shifts in nocturnal glucose control in type 2 diabetes
AU - Basu, Ananda
AU - Joshi, Nisha
AU - Miles, John
AU - Carter, Rickey E.
AU - Rizza, Robert A.
AU - Basu, Rita
N1 - Publisher Copyright:
© 2018 Oxford University Press. All rights reserved.
PY - 2018/10/1
Y1 - 2018/10/1
N2 - Context: A better understanding of nocturnal regulation of glucose homeostasis will provide the framework for designing rational therapeutic strategies to improve the management of overnight glucose in patients with type 2 diabetes (T2D). Objective: To establish the nocturnal pattern and regulation of glucose production (EGP) in humans and to determine whether the pattern is dysregulated in people with T2D. Design: Subjects were infused with [3-3-H] glucose overnight. Arterial blood samples were drawn for hormones and analytes to estimate EGP throughout the night. Deuterium-labeled water was provided to measure gluconeogenesis (GNG) using the hexamethylenetetramine method of Landau. Setting: Mayo Clinic Clinical Research Trials Unit, Rochester, MN, USA. Participants and Interventions: A total of 43 subjects [23 subjects with T2D and 20 nondiabetic (ND) subjects comparable for age and body mass index] were included in this study. Main Outcome(s) Measure(s): Glucose and EGP. Results: Plasma glucose, C-peptide, and glucagon concentrations were higher throughout the night, whereas insulin concentrations were higher in subjects with T2D vs ND subjects at 1:00 and 4:00 AM but similar at 7:00 AM. EGP was higher in the subjects with T2D than in the ND subjects throughout the night (P , 0.001). Glycogenolysis (GGL) fell and GNG rose, resulting in significantly higher (P < 0.001) rates of GNG at 4:00 and 7:00 AMand significantly (P < 0.001) higher rates of GGL at 1:00, 4:00, and 7:00 AM in T2D as compared with ND. Conclusions: These data imply that optimal therapies for T2D for nocturnal/fasting glucose control should target not only the absolute rates of EGP but also the contributing pathways of GGL and GNG sequentially.
AB - Context: A better understanding of nocturnal regulation of glucose homeostasis will provide the framework for designing rational therapeutic strategies to improve the management of overnight glucose in patients with type 2 diabetes (T2D). Objective: To establish the nocturnal pattern and regulation of glucose production (EGP) in humans and to determine whether the pattern is dysregulated in people with T2D. Design: Subjects were infused with [3-3-H] glucose overnight. Arterial blood samples were drawn for hormones and analytes to estimate EGP throughout the night. Deuterium-labeled water was provided to measure gluconeogenesis (GNG) using the hexamethylenetetramine method of Landau. Setting: Mayo Clinic Clinical Research Trials Unit, Rochester, MN, USA. Participants and Interventions: A total of 43 subjects [23 subjects with T2D and 20 nondiabetic (ND) subjects comparable for age and body mass index] were included in this study. Main Outcome(s) Measure(s): Glucose and EGP. Results: Plasma glucose, C-peptide, and glucagon concentrations were higher throughout the night, whereas insulin concentrations were higher in subjects with T2D vs ND subjects at 1:00 and 4:00 AM but similar at 7:00 AM. EGP was higher in the subjects with T2D than in the ND subjects throughout the night (P , 0.001). Glycogenolysis (GGL) fell and GNG rose, resulting in significantly higher (P < 0.001) rates of GNG at 4:00 and 7:00 AMand significantly (P < 0.001) higher rates of GGL at 1:00, 4:00, and 7:00 AM in T2D as compared with ND. Conclusions: These data imply that optimal therapies for T2D for nocturnal/fasting glucose control should target not only the absolute rates of EGP but also the contributing pathways of GGL and GNG sequentially.
UR - http://www.scopus.com/inward/record.url?scp=85054431961&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85054431961&partnerID=8YFLogxK
U2 - 10.1210/jc.2018-00873
DO - 10.1210/jc.2018-00873
M3 - Article
C2 - 30020503
AN - SCOPUS:85054431961
SN - 0021-972X
VL - 103
SP - 3801
EP - 3809
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
IS - 10
ER -