Paradigm shifts in nocturnal glucose control in type 2 diabetes

Ananda Basu, Nisha Joshi, John Miles, Rickey E. Carter, Robert A. Rizza, Rita Basu

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)3801-3809
Number of pages9
JournalJournal of Clinical Endocrinology and Metabolism
Issue number10
StatePublished - Oct 1 2018

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical


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