Paradigm Shifts in Nocturnal Glucose Control in Type 2 Diabetes

J Clin Endocrinol Metab. 2018 Oct 1;103(10):3801-3809. doi: 10.1210/jc.2018-00873.


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 [3-3H] 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 am and 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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Biomarkers / blood*
  • Blood Glucose / analysis*
  • Blood Glucose Self-Monitoring
  • Body Mass Index
  • C-Peptide / analysis*
  • Case-Control Studies
  • Circadian Rhythm*
  • Diabetes Mellitus, Type 2 / physiopathology
  • Diabetes Mellitus, Type 2 / prevention & control*
  • Female
  • Follow-Up Studies
  • Glucagon / analysis*
  • Homeostasis
  • Humans
  • Insulin / analysis*
  • Male
  • Middle Aged
  • Prognosis
  • Sleep / physiology


  • Biomarkers
  • Blood Glucose
  • C-Peptide
  • Insulin
  • Glucagon