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 journalArticle

2 Citations (Scopus)

Abstract

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
Volume103
Issue number10
DOIs
StatePublished - Oct 1 2018

Fingerprint

Medical problems
Type 2 Diabetes Mellitus
Gluconeogenesis
Glucose
Glycogenolysis
Methenamine
C-Peptide
Deuterium
Glucagon
Fasting
Body Mass Index
Homeostasis
Blood
Outcome Assessment (Health Care)
Clinical Trials
Hormones
Insulin
Plasmas
Water
Therapeutics

ASJC Scopus subject areas

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

Cite this

Paradigm shifts in nocturnal glucose control in type 2 diabetes. / Basu, Ananda; Joshi, Nisha; Miles, John; Carter, Rickey E.; Rizza, Robert A.; Basu, Rita.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 103, No. 10, 01.10.2018, p. 3801-3809.

Research output: Contribution to journalArticle

Basu, Ananda ; Joshi, Nisha ; Miles, John ; Carter, Rickey E. ; Rizza, Robert A. ; Basu, Rita. / Paradigm shifts in nocturnal glucose control in type 2 diabetes. In: Journal of Clinical Endocrinology and Metabolism. 2018 ; Vol. 103, No. 10. pp. 3801-3809.
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abstract = "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.",
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