PMID- 33277338
OWN - NLM
STAT- MEDLINE
DCOM- 20210510
LR  - 20220202
IS  - 1939-327X (Electronic)
IS  - 0012-1797 (Print)
IS  - 0012-1797 (Linking)
VI  - 70
IP  - 2
DP  - 2021 Feb
TI  - Baseline Assessment of Circulating MicroRNAs Near Diagnosis of Type 1 Diabetes 
      Predicts Future Stimulated Insulin Secretion.
PG  - 638-651
LID - 10.2337/db20-0817 [doi]
AB  - Type 1 diabetes is an autoimmune disease resulting in severely impaired insulin 
      secretion. We investigated whether circulating microRNAs (miRNAs) are associated 
      with residual insulin secretion at diagnosis and predict the severity of its 
      future decline. We studied 53 newly diagnosed subjects enrolled in placebo groups 
      of TrialNet clinical trials. We measured serum levels of 2,083 miRNAs, using RNA 
      sequencing technology, in fasting samples from the baseline visit (<100 days from 
      diagnosis), during which residual insulin secretion was measured with a mixed 
      meal tolerance test (MMTT). Area under the curve (AUC) C-peptide and peak 
      C-peptide were stratified by quartiles of expression of 31 miRNAs. After 
      adjustment for baseline C-peptide, age, BMI, and sex, baseline levels of 
      miR-3187-3p, miR-4302, and the miRNA combination of miR-3187-3p/miR-103a-3p 
      predicted differences in MMTT C-peptide AUC/peak levels at the 12-month visit; 
      the combination miR-3187-3p/miR-4723-5p predicted proportions of subjects 
      above/below the 200 pmol/L clinical trial eligibility threshold at the 12-month 
      visit. Thus, miRNA assessment at baseline identifies associations with C-peptide 
      and stratifies subjects for future severity of C-peptide loss after 1 year. We 
      suggest that miRNAs may be useful in predicting future C-peptide decline for 
      improved subject stratification in clinical trials.
CI  - (c) 2020 by the American Diabetes Association.
FAU - Snowhite, Isaac
AU  - Snowhite I
AD  - Diabetes Research Institute, Leonard M. Miller School of Medicine, University of 
      Miami, Miami, FL.
FAU - Pastori, Ricardo
AU  - Pastori R
AD  - Diabetes Research Institute, Leonard M. Miller School of Medicine, University of 
      Miami, Miami, FL.
AD  - Division of Endocrinology and Metabolism, Department of Medicine, Leonard M. 
      Miller School of Medicine, University of Miami, Miami, FL.
FAU - Sosenko, Jay
AU  - Sosenko J
AUID- ORCID: 0000-0002-7204-8367
AD  - Division of Endocrinology and Metabolism, Department of Medicine, Leonard M. 
      Miller School of Medicine, University of Miami, Miami, FL.
FAU - Messinger Cayetano, Shari
AU  - Messinger Cayetano S
AD  - Department of Public Health Sciences, Leonard M. Miller School of Medicine, 
      University of Miami, Miami, FL.
FAU - Pugliese, Alberto
AU  - Pugliese A
AUID- ORCID: 0000-0002-7211-0319
AD  - Diabetes Research Institute, Leonard M. Miller School of Medicine, University of 
      Miami, Miami, FL apuglies@med.miami.edu.
AD  - Division of Endocrinology and Metabolism, Department of Medicine, Leonard M. 
      Miller School of Medicine, University of Miami, Miami, FL.
AD  - Department of Microbiology and Immunology, Leonard M. Miller School of Medicine, 
      University of Miami, Miami, FL.
LA  - eng
SI  - figshare/10.2337/figshare.13281188
GR  - U01 DK085476/DK/NIDDK NIH HHS/United States
GR  - U01 DK061010/DK/NIDDK NIH HHS/United States
GR  - U01 DK106993/DK/NIDDK NIH HHS/United States
GR  - U01 DK103282/DK/NIDDK NIH HHS/United States
GR  - UC4 DK106993/DK/NIDDK NIH HHS/United States
GR  - U01 DK061042/DK/NIDDK NIH HHS/United States
GR  - U01 DK085509/DK/NIDDK NIH HHS/United States
GR  - UC4 DK117009/DK/NIDDK NIH HHS/United States
GR  - U01 DK085466/DK/NIDDK NIH HHS/United States
GR  - U01 DK103153/DK/NIDDK NIH HHS/United States
GR  - U01 DK061058/DK/NIDDK NIH HHS/United States
GR  - U01 DK085453/DK/NIDDK NIH HHS/United States
GR  - UL1 TR002736/TR/NCATS NIH HHS/United States
GR  - U01 DK106984/DK/NIDDK NIH HHS/United States
GR  - U01 DK085499/DK/NIDDK NIH HHS/United States
GR  - U01 DK107013/DK/NIDDK NIH HHS/United States
GR  - U01 DK103266/DK/NIDDK NIH HHS/United States
GR  - U01 DK107014/DK/NIDDK NIH HHS/United States
GR  - U01 DK106994/DK/NIDDK NIH HHS/United States
GR  - U01 DK061034/DK/NIDDK NIH HHS/United States
GR  - U01 DK085461/DK/NIDDK NIH HHS/United States
GR  - U01 DK103180/DK/NIDDK NIH HHS/United States
GR  - U01 DK085465/DK/NIDDK NIH HHS/United States
GR  - U01 DK085504/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20201204
PL  - United States
TA  - Diabetes
JT  - Diabetes
JID - 0372763
RN  - 0 (C-Peptide)
RN  - 0 (Circulating MicroRNA)
RN  - 0 (Insulin)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - C-Peptide/blood
MH  - Child
MH  - Circulating MicroRNA/*blood
MH  - Diabetes Mellitus, Type 1/blood/*diagnosis
MH  - Female
MH  - Humans
MH  - Insulin/*blood
MH  - Insulin Secretion/*physiology
MH  - Male
MH  - Meals
MH  - Young Adult
PMC - PMC7881864
EDAT- 2020/12/06 06:00
MHDA- 2021/05/11 06:00
PMCR- 2022/02/01
CRDT- 2020/12/05 05:26
PHST- 2020/08/07 00:00 [received]
PHST- 2020/11/24 00:00 [accepted]
PHST- 2020/12/06 06:00 [pubmed]
PHST- 2021/05/11 06:00 [medline]
PHST- 2020/12/05 05:26 [entrez]
PHST- 2022/02/01 00:00 [pmc-release]
AID - db20-0817 [pii]
AID - 200817 [pii]
AID - 10.2337/db20-0817 [doi]
PST - ppublish
SO  - Diabetes. 2021 Feb;70(2):638-651. doi: 10.2337/db20-0817. Epub 2020 Dec 4.