Paradigm Shifts in Nocturnal Glucose Control in Type 2 Diabetes

被引:11
作者
Basu, Ananda [1 ]
Joshi, Nisha [2 ]
Miles, John [3 ]
Carter, Rickey E. [4 ]
Rizza, Robert A. [2 ]
Basu, Rita [1 ]
机构
[1] Univ Virginia, Sch Med, Dept Endocrinol, Charlottesville, VA 22904 USA
[2] Mayo Clin, Endocrine Res Unit, Rochester, MN 55905 USA
[3] Univ Kansas, Med Ctr, Div Endocrinol Metab & Genet, Kansas City, KS 66160 USA
[4] Mayo Clin, Dept Hlth Sci Res, Jacksonville, FL 32216 USA
基金
美国国家卫生研究院;
关键词
HEPATIC GLYCOGEN; FASTING HYPERGLYCEMIA; INTRAVENOUS GLUCOSE; NONDIABETIC HUMANS; DIURNAL PATTERN; INSULIN ACTION; GLUCONEOGENESIS; METABOLISM; MELLITUS; PEOPLE;
D O I
10.1210/jc.2018-00873
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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-H-3] 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 A Mand significantly (P < 0.001) higher rates of GGL at 1:00, 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.
引用
收藏
页码:3801 / 3809
页数:9
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