PMID- 33033064
OWN - NLM
STAT- MEDLINE
DCOM- 20210510
LR  - 20220102
IS  - 1939-327X (Electronic)
IS  - 0012-1797 (Print)
IS  - 0012-1797 (Linking)
VI  - 70
IP  - 1
DP  - 2021 Jan
TI  - Effect of Mild Physiologic Hyperglycemia on Insulin Secretion, Insulin Clearance, 
      and Insulin Sensitivity in Healthy Glucose-Tolerant Subjects.
PG  - 204-213
LID - 10.2337/db20-0039 [doi]
AB  - The aim of the current study was to evaluate the effect of sustained physiologic 
      increase of  approximately 50 mg/dL in plasma glucose concentration on insulin secretion in 
      normal glucose-tolerant (NGT) subjects. Twelve NGT subjects without family 
      history of type 2 diabetes mellitus (T2DM; FH-) and 8 NGT with family history of 
      T2DM (FH+) received an oral glucose tolerance test and two-step hyperglycemic 
      clamp (100 and 300 mg/dL) followed by intravenous arginine bolus before and after 
      72-h glucose infusion. Fasting plasma glucose increased from 94 +/- 2 to 142 +/- 4 
      mg/dL for 72 h. First-phase insulin secretion (0-10 min) increased by 70%, while 
      second-phase insulin secretion during the first (10-80 min) and second (90-160 
      min) hyperglycemic clamp steps increased by 3.8-fold and 1.9-fold, respectively, 
      following 72 h of physiologic hyperglycemia. Insulin sensitivity during 
      hyperglycemic clamp declined by  approximately 30% and  approximately 55% (both P < 0.05), respectively, 
      during the first and second hyperglycemic clamp steps. Insulin secretion/insulin 
      resistance (disposition) index declined by 60% (second clamp step) and by 62% 
      following arginine (both P < 0.005) following 72-h glucose infusion. The effect 
      of 72-h glucose infusion on insulin secretion and insulin sensitivity was similar 
      in subjects with and without FH of T2DM. Following 72 h of physiologic 
      hyperglycemia, metabolic clearance rate of insulin was markedly reduced (P < 
      0.01). These results demonstrate that sustained physiologic hyperglycemia for 72 
      h 1) increases absolute insulin secretion but impairs beta-cell function, 2) causes 
      insulin resistance, and 3) reduces metabolic clearance rate of insulin.
CI  - (c) 2020 by the American Diabetes Association.
FAU - Merovci, Aurora
AU  - Merovci A
AD  - Division of Diabetes, Department of Medicine, University of Texas Health Science 
      Center, San Antonio, TX.
FAU - Tripathy, Devjit
AU  - Tripathy D
AD  - Division of Diabetes, Department of Medicine, University of Texas Health Science 
      Center, San Antonio, TX.
AD  - Audie L. Murphy VA Hospital, South Texas Veterans Heath Care System, Foundation 
      for Advancing Veterans' Health Research, San Antonio, TX.
FAU - Chen, Xi
AU  - Chen X
AD  - Division of Diabetes, Department of Medicine, University of Texas Health Science 
      Center, San Antonio, TX.
FAU - Valdez, Ivan
AU  - Valdez I
AD  - Division of Diabetes, Department of Medicine, University of Texas Health Science 
      Center, San Antonio, TX.
FAU - Abdul-Ghani, Muhammad
AU  - Abdul-Ghani M
AUID- ORCID: 0000-0003-4556-1787
AD  - Division of Diabetes, Department of Medicine, University of Texas Health Science 
      Center, San Antonio, TX.
FAU - Solis-Herrera, Carolina
AU  - Solis-Herrera C
AUID- ORCID: 0000-0002-6215-9418
AD  - Division of Diabetes, Department of Medicine, University of Texas Health Science 
      Center, San Antonio, TX.
FAU - Gastaldelli, Amalia
AU  - Gastaldelli A
AUID- ORCID: 0000-0003-2594-1651
AD  - Division of Diabetes, Department of Medicine, University of Texas Health Science 
      Center, San Antonio, TX.
FAU - DeFronzo, Ralph A
AU  - DeFronzo RA
AUID- ORCID: 0000-0002-8581-6273
AD  - Division of Diabetes, Department of Medicine, University of Texas Health Science 
      Center, San Antonio, TX albarado@uthscsa.edu.
AD  - Audie L. Murphy VA Hospital, South Texas Veterans Heath Care System, Foundation 
      for Advancing Veterans' Health Research, San Antonio, TX.
LA  - eng
GR  - R01 DK024092/DK/NIDDK NIH HHS/United States
GR  - R56 DK024092/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20201008
PL  - United States
TA  - Diabetes
JT  - Diabetes
JID - 0372763
RN  - 0 (Blood Glucose)
RN  - 0 (Insulin)
SB  - IM
MH  - Adult
MH  - Blood Glucose/*metabolism
MH  - Female
MH  - Glucose Clamp Technique
MH  - Glucose Tolerance Test
MH  - Healthy Volunteers
MH  - Humans
MH  - Hyperglycemia/blood/*metabolism
MH  - Insulin/*metabolism
MH  - Insulin Resistance/*physiology
MH  - Insulin Secretion/*physiology
MH  - Male
MH  - Middle Aged
PMC - PMC7881846
EDAT- 2020/10/10 06:00
MHDA- 2021/05/11 06:00
PMCR- 2022/01/01
CRDT- 2020/10/09 05:31
PHST- 2020/02/12 00:00 [received]
PHST- 2020/10/06 00:00 [accepted]
PHST- 2020/10/10 06:00 [pubmed]
PHST- 2021/05/11 06:00 [medline]
PHST- 2020/10/09 05:31 [entrez]
PHST- 2022/01/01 00:00 [pmc-release]
AID - db20-0039 [pii]
AID - 200039 [pii]
AID - 10.2337/db20-0039 [doi]
PST - ppublish
SO  - Diabetes. 2021 Jan;70(1):204-213. doi: 10.2337/db20-0039. Epub 2020 Oct 8.