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Journal Club
Tripathy D1, Cobb JE, Gall W, Adam KP, George T, Schwenke DC,
Banerji M, Bray GA, Buchanan TA, Clement SC, Henry RR, Kitabchi
AE, Mudaliar S, Ratner RE, Stentz FB, Reaven PD, Musi N,
Ferrannini E, DeFronzo RA.
A Novel Insulin Resistance Index to Monitor Changes in Insulin
Sensitivity and Glucose Tolerance: the ACT NOW Study.
J Clin Endocrinol Metab. 2015 Jan 20:jc20143824.
2015年1月29日 8:30-8:55
８階医局
埼玉医科大学総合医療センター内分泌・糖尿病内科
Department of Endocrinology and Diabetes,
Saitama Medical Center, Saitama Medical University
松田昌文
Matsuda, Masafumi
Prevention of Diabetes Mellitus
Trial
publication
follow-up,
year
No. of new
No.(total)
on-set of DM
drug
event
per 1000
person-years
control
37
21
16
391
397
393
105.1
58.8
45.2
37
122
121.3
No. of new
No.(total)
on-set of DM
event
per 1000
person-years
Thiazolidine
*DPP
2005
0.9
Troglitazone
10
387
28.7
Placebo
Metformin
ILS
TRIPOD
2002
2.5
Troglitazone
17
114
59.6
Placebo
PIPOD
2006
3.0
Pioglitazone
11
86
42.6
-
*DREAM
2006
3.0
Rosiglitazone
306
2365
43.1
Placebo
686
2634
86.8
*ACTNOW
2008
4.0
Pioglitazone
10
303
8.3
Placebo
45
299
37.6
*CANOE
2010
3.9
Met+Rosi
14
103
34.9
Placebo
41
104
101.1
Other (α-GI, statin, fibrate, glinide)
WOSCOP
2001
5
Pravastation
57
2999
3.8
Placebo
82
3975
5.5
*STOP- NIDDM
2002
3.3
Acarbose
221
682
98.2
Placebo
285
686
125.9
BIP
2004
6.2
Bezafibrate
66
156
68.2
Placebo
80
147
87.8
*VICTORY
2009
4
Voglibose
50
897
13.9
Placebo
106
881
30.0
*NAVIGATOR
2010
6.5
Nateglinide
1674
3726
69.1
Placebo
1580
3747
64.9
Matsuda M.;GEKKAN TOUNYOUBYOU;2,16-22,2010 2:16-22, 2010.
EFFECT OF PIOGLITAZONE AND PLACEBO ON
MATSUDA INDEX OF INSULIN SENSITIVITY
Placebo
Pioglitazone
10
Matsuda Index
8
6
Insulin sensitivity as measured with the
Matsuda index increased more with
pioglitazone than with placebo (4.31±0.24
to 7.65±0.34 vs. 4.31±0.30 to 5.23±0.31,
P<0.001).
P<0.001
4
2
0
Pre
Post
Pre
Post
72％reduction!
N Engl J Med 2011;364:1104-15.
1Texas
Diabetes Institute, San Antonio, Texas
of Texas Health Science Center, San Antonio, Texas
3Phoenix VA Health Care System, Phoenix, Arizona
4College of Nursing and Health Innovation, Arizona State University, Phoenix, Arizona
5SUNY Health Science Center at Brooklyn, Brooklyn, New York
6Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, Louisiana
7University of Southern California Keck School of Medicine, Los Angeles, California
8Division of Endocrinology and Metabolism, Georgetown University, Washington, D.C.
9VA San Diego Healthcare System, San Diego, California
10University of California at San Diego, San Diego, California
11Division of Endocrinology, Diabetes, and Metabolism, University of Tennessee, Memphis, Tennessee
12Medstar Research Institute, Hyattsville, Maryland
13Cardiometabolic Risk Unit, Institute of Clinical Physiology, Pisa, Italy
In a stepwise multiple-variable analysis, only HbA1c and
β-cell function (ln[log] insulin secretion/insulin resistance
index) predicted the development of diabetes (r = 0.49;
P < 0.0001).
2University
Diabetes Care 36:3607–3612, 2013
J Clin Endocrinol Metab. 2015 Jan 20:jc20143824.
1Texas
Diabetes Institute, University of Texas Health Science Center and S Texas Veterans Health Care System, Audie L. Murphy
Division, San Antonio, TX;
2Metabolon, Inc. 617 Davis Dr, Ste. 400, Durham, NC 27713
3Phoenix VA Health Care System, Phoenix, AZ,
4College of Nursing and Health Care Innovation., AZ State University, Phoenix, AZ;
5Suny Health Science Center at Brooklyn, Brooklyn, NY;
6Pennington Biomedical Research Center/LSU, Baton Rouge, LA;
7University of Southern California Keck School of Medicine, Los Angeles, CA,
8VA San Diego Healthcare System and University of California at San Diego;
9University of Tennessee, Division of Endocrinology, Diabetes and Metabolism, Memphis, TN;
10Inova Fairfax Hospital, Falls Church, VA;
11Medstar Research Institute;
12Department of Clinical & Experimental Medicine, University of Pisa School of Medicine, Pisa, Italy
Objective:
To test the clinical utility of Quantose MQ to
monitor changes in insulin sensitivity following
pioglitazone therapy in prediabetic subjects. MQ is
derived from fasting measurements of insulin, αhydroxybutyrate, linoleoyl-glycerophosphocholine,
and oleate, three non-glucose metabolites shown
to correlate with insulin-stimulated glucose
disposal.
Research design and methods:
Participants were 428 of the total of 602 ACT
NOW IGT subjects randomized to pioglitazone
(45 mg/day) or placebo and followed for, 2.4
years. At baseline and study end fasting plasma
metabolites required for determination of
Quantose, HbA1c, and OGTT with frequent
plasma insulin and glucose measurements to
calculate, Matsuda Index of insulin sensitivity
were obtained.
The Quantose M index (MQ) is derived from a multiple linear regression based on
fasting measurements (logarithmically transformed) of plasma a-HB, L-GPC, oleic
acid, and insulin, as previously described (20). We chose the metabolites which
had the highest correlation with insulin sensitivity obtained from
hyperinsulinemic euglcyemic clamp studies a-HB –0.36, LGPC 0.33, and oleate –
0.22 (20). MQ is designed to estimate the clamp-derived M value.
Cobb J, Gall WE,AdamKP, Nakhle P, Button E, Hathorn J, Lawton K,
Milburn M, Perichon R, Mitchell M, Natali A, Ferrannini E. A novel fasting
blood test for insulin resistance and prediabetes. J Diab Sci Tech.
2013;7:100–110.
Figure 1. Baseline (left panels) and change at close-out (right panels) values for Matsuda Index (top panels) and
Quantose MQ (bottom panels) according to glucose tolerance status at close-out
(NGTnormal glucose tolerance, IGTimpaired glucose tolerance, T2Dtype 2 diabetes) in subjects randomized to
pioglitazone or placebo. Plots are mean 95% confidence intervals.
#P = .008 for the difference between NGT and IGT/T2D;
* P = .01 for the difference between NGT and IGT/T2D and
§ P =.01 for the difference between pioglitazone and placebo by 2-way ANOVA.
During a median follow-up of 2.4 years, 42 individuals in the placebo group and 12
in the pioglitazone group developed diabetes (HR = 0.25, 95%CI = 0.13– 0.50,
P<.0001). Of the other 374 subjects, 181 regressed to NGT (110 with pioglitazone
vs 71 with placebo, P <.02).
Figure 2. Relationship between close-out changes in Quantose MQ and Matsuda
Index in subjects randomized to pioglitazone or placebo. The best fit is linear in
both groups (r=0.69, P <.0001 for pioglitazone, and r=0.77, P<.0001 for placebo);
the fitted line for the pioglitazone group is significantly (P<.01) different from that
of the placebo group.
Supplemental Figure 1 - Change at close-out for Quantose MQ components according
to glucose tolerance status at close-out (NGT=normal glucose tolerance, IGT=impaired
glucose tolerance, T2D=type 2 diabetes) in subjects randomized to pioglitazone. Plots
are mean + 95% confidence intervals. # p<0.0005 and * p<0.005 for the difference
between NGT and IGT/T2D by 2-way ANOVA.
Results:
Pioglitazone treatment lowered IGT conversion to diabetes
(HR=0.25, 95%CI = 0.13–0.50, p<0.0001). While HbA1c did
not track with insulin sensitivity, MQ increased in pioglitazonetreated subjects (by 1.45[3.45] mg.min−1.kgwbm−1
(median[interquartile range]), (p<0.001 vs placebo) as did,
Matsuda Index (by 3.05[4.77] units, p<0.0001). MQ correlated
with Matsuda Index at baseline and change in Matsuda
Index from baseline (rho's of 0.85 and 0.79, respectively,
p<0.0001) and was progressively higher across close-out
glucose tolerance status (diabetes, IGT, NGT). In logistic
models including only anthropometric and fasting
measurements, MQ outperformed both Matsuda and fasting
insulin in predicting incident diabetes.
Conclusions:
In IGT subjects, Quantose MQ parallels changes
in insulin sensitivity and glucose tolerance with
pioglitazone therapy. Due to its strong correlation
with improved insulin sensitivity and its ease of
use, Quantose MQ may serve as a useful clinical
test to identify and monitor therapy in insulin
resistant patients.
Message
インスリン感受性指標か、血糖上昇のリスク因子か
位置づけは今一つはっきりとはしないが、血糖以外
から血糖について予言するというおもしろい指標が
提唱された。
いろいろ測定しておくのは面倒かもしれない。（が
糖負荷をしなくていのが面白い！）
Matsuda index との対比があるが、インスリン分泌
能がインスリン抵抗性よりも大切なはずで、本来は
disposition indexを計算するところと思うが。
一番重要なのは、空腹時のインスリン感受性改善が
インスリン分泌を回復させそう！リンクにQM計算に
用いた物質が関係しそう。

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