Slide

1. FASTING TRIGLYCERIDES &
GLUCOSE INDEX
as a Diagnostic Test for
INSULIN RESISTANCE in Young Adults
Fernando Guerrero-Romero, Rafael Villalobos-Molina, J. Rafael Jimenez-Flores,
Luis E. Simental-Mendia, Rene Mendez-Cruz,b Miguel Murguıa-Romero, and
Martha Rodrıguez-Moran
Shendy – Fatma – Riska
Pembimbing: Dr. dr. Himawan Sanusi, SpPD-KEMD
Archives of Medical Research 47 (2016) 382-387
http://dx.doi.org/10.1016/j.arcmed.2016.08.012

2. INTRODUCTION
INSULIN RESISTANCE (IR)
• Precedes development of type 2 diabetes and
cardiovascular disease
 EARLY detection !!!
• Gold standard :
Euglycemic-hyperinsulinemic clamp
(Expensive & not available)
• Surrogate indices :
HOMA-IR
TyG index
2

3. INTRODUCTION
TyG index
• Different ethnic groups
– Mexican-Americans and Caucasian descents
– Koreans
– Chinese
– Mexican adults
– Italian
– Brazilian adults
 Useful  identification of IR
Best cost/performance ratio
• Younger adults ??
3

4. INTRODUCTION
Objective :
To evaluate
the TyG index
as a diagnostic test for IR
in healthy young adults
4

5. MATERIALS & METHODS
• Eligible subjects, healthy young adults
• College students
• 18 – 23 years
• Exclusion criteria:
– Pregnancy
– Chronic illness
– Malignancy
– Diabetes
– Intake of drugs during the previous 3 months
5

6. MATERIALS & METHODS
1st step
• Randomized n = 75
• TyG index vs the euglycemic-
hyperinsulinemic clamp test
2nd step
• Diagnostic concordance of TyG index and
HOMA-IR  overall population
6

7. MATERIALS & METHODS
• IR
– Euglycemic-hyperinsulinemic clamp  M rate ≥ 2.8
– HOMA-IR index ≥ 2.9
• Obesity
– BMI ≥ 30 kg/m2
• Overweight
– BMI ≥ 25 kg/m2
• Normal weight
– 19 kg/m2 ≤ BMI < 25 kg/m2
7

8. MATERIALS & mETHODS
8
𝐇𝐎𝐌𝐀 − 𝐈𝐑 =
𝐟𝐚𝐬𝐭𝐢𝐧𝐠 𝐢𝐧𝐬𝐮𝐥𝐢𝐧 (𝐔 𝐦𝐋) × 𝐟𝐚𝐬𝐭𝐢𝐧𝐠 𝐠𝐥𝐮𝐜𝐨𝐬𝐞 (𝐦𝐦𝐨𝐥 𝐋)
𝟐𝟐. 𝟓
TyG index =
Ln [fasting triglycerides (mg/dL) x fasting glucose (mg/dL)] / 2
𝐁𝐌𝐈 =
𝐰𝐞𝐢𝐠𝐡𝐭 (𝐤𝐠)
𝐡𝐞𝐢𝐠𝐡𝐭 (𝐦) 𝟐

9. MATERIALS & METHODS
• Whole blood
• 10 – 12 h overnight fasting
– Triglycerides
– Glucose
– Insulin
9

10. RESULTS
5,538 healthy young adults
Average age 19.2 ± 1.4 years
BMI 24.2 ± 4.4 kg/m2
10
3,795 (68.5%)
1,743 (31.5%)
Normal weight 3,632 (65,6%)
Overweight 1,355 (24.5%)
Obesity 551 (9.9%)

11. RESULTS
11
A total of 5,538 healthy young adults with an average age of 19.2 ± 1.4 years and
BMI of 24.2 ± 4.4 kg/m2 were enrolled. Of these subjects, 3,795 (68.5%) were
men and 1,743 (31.5%) women

12. RESULTS
75 participants
 45 (60%)
 30 (40%)
Normal weight 50 (66.7%)
Overweight 15 (20%)
Obesity 10 (13.3%)
12
TyG index vs euglycemic hyperinsulinemic
clamp

13. RESULTS
13
A total of 5,538 healthy young adults with an average age of 19.2 ± 1.4 years and
BMI of 24.2 ± 4.4 kg/m2 were enrolled. Of these subjects, 3,795 (68.5%) were
men and 1,743 (31.5%) women

14. RESULTS
• Pearson’s correlation coefficient between TyG index
and M rates :
  -0.875 ( p <0 .0001)
  -0.834 ( p < 0.0005)
• ROC scatter plot revealed that the best value of TyG
index for diagnosis of IR
  4.55
 4.68
14

15. RESULTS
15
Figure 1. Receiver operating characteristic curve. Sensitivity represents
true-positive results and 1-specificity the false-positive results. The best
TyG value for diagnosis of insulin resistance was 4.55 (sensitivity 0.687)
and 4.68 (sensitivity 0.673) for women (B) and men (A).



16. RESULTS
16

17. RESULTS
17
HOMA-IR
346
(9.1%)
278
(15.9%)
TyG index
374
(9.8%)
304
(17.4%)
Insulin resistance

18. RESULTS
Pearson correlation between the TyG and HOMA-IR
  0.932 ( p < 0.0005)
  0.918 ( p < 0.0005)
18

19. results
19

20. DISCUSSION
TyG index
•  NPV
•  NLR
• High diagnostic concordance with HOMA-IR
 Screening IR in young adults
Not a diagnostic test for confirming IR
20

21. DISCUSSION
TyG index
• Insulin  not available in all laboratories
• Minimize the cost of screening and expanding
its coverage
 Promissory tool for screening IR in
young adults
21

22. DISCUSSION
TyG index
6.2%
normal-weight
participants
HOMA-IR
5.6%
normal-weight
participants
22
Impaired insulin sensitivity
TyG index  useful for screening of
metabolically obese but normal-weight young adults

23. CONCLUSION
23
TyG index
High NPV
Low NLR
High diagnostic concordance
with HOMA-IR
Screening IR in young adults

26. 26

27. For the euglycemic-hyperinsulinemic clamp technique, two points of
venous access were established. The first was placed in a retrograde
position into any vein in the subject’s hand through a 23-gauge
catheter to obtain blood samples. The hand was wrapped with a
thermal pillow until reaching a temperature above 40 C to improve the
amount of oxygen in venous blood. The second point of venous access
was established in the contralateral arm with a 20-gauge catheter for
infusion. Insulin (Humulin R; Eli Lilly Co., Mexico City, Mexico) was
given as a primed continuous infusion calculated to raise the plasma
insulin concentration to 100U/m2, followed by an insulin infusion rate
fixed at 40U/min/m2.Aconstant blood glucose level was maintained
(with a coefficient of variation5%)throughout the 120- min study by
infusing 10% glucose at various rates according to blood glucose
measurements performed at 5-min intervals. At the end of the clamp
procedure, the 10% glucose infusion was maintained for 30 min to
avoid hypoglycemia. Total glucose metabolism (M) rate was calculated
to evaluate insulin sensitivity (9). All of the studies began at 0800 h
after a 10- to 12-h overnight fast.Mrates of at least 2.8 defined insulin
resistance. 27

28. • Hyperinsulinemic Euglycemic Glucose Clamp Technique. After an
overnight fast, insulin is infused intravenously at a constant rate that
may range from 5~120 mU/m2/min (dose per body surface area per
minute). This constant insulin infusion results in a new steady-state
insulin level that is above the fasting level (hyperinsulinemic). As a
consequence, glucose disposal in skeletal muscle and adipose tissue is
increased while hepatic glucose production is suppressed. Under these
conditions, a bedside glucose analyzer is used to frequently monitor
blood glucose levels at 5~10 min intervals while 20% dextrose is given
intravenously at a variable rate in order to "clamp" blood glucose
concentrations in the normal range (euglycemic). An infusion of
potassium phosphate is also given to prevent hypokalemia resulting
from hyperinsulinemia and increased glucose disposal. After several
hours of constant insulin infusion, steady-state conditions can typically
be achieved for plasma insulin, blood glucose, and the glucose infusion
rate (GIR). Assuming that the hyperinsulinemic state is sufficient to
completely suppress hepatic glucose production, and since there is no
net change in blood glucose concentrations under steady-state clamp
conditions, the GIR must be equal to the glucose disposal rate (M).
Thus, whole body glucose disposal at a given level of hyperinsulinemia
can be directly determined (Adopted from Muniyappa R, et al. Am J
Physiol Endocrinol Metab 294:E15-26, 2008).
28

30. Jenis Pemeriksaan : Trigliserida
Metode : PAP – GPO
Prinsip : Trigliserida ditentukan setelah hidrolisis
enzim dengan lemak. Indikator quinoneimine dibentuk dari
hidrogen peroksida, 4 – aminoantypirine dan 4 – klorofenol di
bawah pengaruh katalisis peroksidase.
Trigliserida lipases gliserol + asam lemak
Gliserol + ATP GK gliserol-3-fosfat + ADP
Gliserol-3-fostat + O2 GPO dihidroksiaseton fosfat + H2O2
H2O2 + aminoantypirine POD quinoneimine + HCl + H2O +
4-Klorofenol

34. Metode dan prinsip tes glukosa
• Metode enzimatik :glucose oxidase / hexokinase
• Prinsip tes:
Darah kapiler diserap ke dalam strip tes, kemudian
mengalir ke area tes dan bercampur dengan reagen
untuk memulai proses pengukuran. Enzim Glucose
dehydrogenase dan koenzim dalam strip tes
mengkonversi glukosa dalam sampel darah menjadi
glukonolakton. Reaksi tersebut menghasilkan listrik
DC yang tidak berbahaya sehingga Meter mampu
mengukur gula darah.

37. Pengatur kadar glukosa dalam darah

38. MEKANISME KERJA INSULIN

53. Pemilihan hipotesis korelatif
Variabel 1 Variabel 2 Uji korelasi yang dipilih
Nominal Nominal Koefisien kontingensi, Lambda
Nominal Ordinal Koefisien kontingensi, Lambda
Ordinal Ordinal Spearman, Gamma, Somers’d
Ordinal Numerik Spearman
Numerik Numerik Pearson
53

54. Panduan interpretasi hasil uji hipotesis berdasarkan
kekuatan korelasi, nilai p dan arah korelasi
No Paramter Nilai Interpretasi
1
Kekuatan
korelasi (r)
0,0 sd < 0,2 Sangat lemah
0,2 sd < 0,4 Lemah
0,4 sd < 0,6 Sedang
0,6 sd < 0,8 Kuat
0,8 sd 1 Sangat kuat
2 Nilai p
P < 0,05 Terdapat korelasi yang bermakna antara dua
variabel yang diuji
P > 0,05 Tidak terdapat korelasi yang bermakna
antara dua variabel yang diuji
3 Arah korelasi
+ (positif) Searah, semakin besar nilai satu variabel
semakin besar pula nilai variabel lainnya.
- (negatif) Berlawanan arah. Semakin besar nilai satu
variabel, semakin kecil nilai variabel lainnya.
54

56. 56
Sehat Sakit
Positif TP
(true positive)
FP
(false positive)
Negatif FN
(false negative)
TN
(true negative)
Sensitivity =
𝐓𝐏
(𝐓𝐏 + 𝐅𝐍)
Specificity =
𝐓𝐍
(𝐓𝐍 + 𝐅𝐏)
PPV =
𝐓𝐏
(𝐓𝐏 + 𝐅𝐏)
(positive predictive value)
NPV =
𝐓𝐍
(𝐓𝐍 + 𝐅𝐍)
(negative predictive value)
PLR =
𝐒𝐞𝐧𝐬𝐢𝐭𝐢𝐯𝐢𝐭𝐲
(𝟏 −𝐒𝐩𝐞𝐜𝐢𝐟𝐢𝐜𝐢𝐭𝐲)
(positive likelihood ratio)
NLR =
(𝟏 − 𝐒𝐞𝐧𝐬𝐢𝐭𝐢𝐯𝐢𝐭𝐲)
𝐒𝐩𝐞𝐜𝐢𝐟𝐢𝐜𝐢𝐭𝐲
(negative likelihood ratio)

57. 57

60. 60
d