Paradigm Shifts in Nocturnal Glucose Control in Type 2 Diabetes.

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 [3-3H] 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.

• Authors: Ananda Basu, Nisha Joshi, John Miles, Rickey E Carter, Robert A Rizza, Rita Basu
• Journal: The Journal of clinical endocrinology and metabolism (J Clin Endocrinol Metab) Vol. 103 Issue 10 Pg. 3801-3809 (10 01 2018) ISSN: 1945-7197 [Electronic] United States
• PMID: 30020503 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

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

Topics

• 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, prevention & control)
• Female
• Follow-Up Studies
• Glucagon (analysis)
• Homeostasis
• Humans
• Insulin (analysis)
• Male
• Middle Aged
• Prognosis
• Sleep (physiology)