An ton v Hiu qu

Ca Insulin Analogue trong iu tr

i Tho ng Tp 2

GS.TS. Nguyn Hi Thy

Trng i Hc Y Dc Hu

SlametS 1
 t vn

SlametS 2
 T ghi nhn 1552 BC

Georg Moritz Ebers (1837 -1898) v bn tho c ch Ai Cp

SlametS 3
 M t lm sng T thi k c i

Aretaeus of Cappadocia v Hippocrates

T c xem nh mt n t hnh v v phng cu cha
SlametS 4
SlametS 5
 Sir Frederick Grant Banting
(November 14, 1891 February 21, 1941)
Savior of Humanity
 Bnh nhn s dng insulin u tin trn th gii
11/01/1922

John Leonard Thompson (1908-1935) nhim toan cetone ch cht v

c cu sng nh s dng mi insulin u tin trn th gii.

SlametS 8
 Elizabeth Hughes Gossett (1907-1981)
Ngi nhn huy chng chch insulin trn 50 nm
SlametS 9
 Tin trnh ca T tp 2
Glucose (mg/dL)
350 Postmeal Glucose
Prediabetes Diabetes
300
(Obesity, IFG, IGT) diagnosis
250
200
Fasting glucose
150
100
50
-15 -10 -5 0 5 10 15 20 25 30
250 Years
Relative Amount

200 -cell failure Insulin resistance

150
100
50 Insulin level

0
-15 -10 -5 0 5 10 15 20 25 30
Onset Years
diabetes
Macrovascular changes
Clinical
features Microvascular changes
IFG, impaired fasting glucose;
Kendall DM, et al. Am J Med 2009;122:S37-S50.
IGT, impaired glucose tolerance.
Kendall DM, et al. Am J Manag Care 2001;7(suppl):S327-S343.
UKPDS: kim sot ng huyt km dn theo thi gian

Thng quy (n=200) Insulin (n=199)

9 Glibenclamide (n=148) Chlorpropamide (n=129)

Metformin (n=181)
HbA1C trung bnh (%)

7
Mc tiu theo ADA (7.0%)

6 Gii hn trn ca bnh thng (6.2%)

0
0 2 4 6 8 10
Thi gian t khi chia ngu nhin vo cc nhm iu tr (nm)
ADA=American Diabetes Association; HbA1c=hemoglobin A1c
Adapted from UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998; 352: 854865.
 Phi hp thuc trong T tp 2

Sulfonylureas

Alpha-glucosidase
Biguanides Inhibitors

Meglitinide Thiazolidinediones

Insulin
Khng phi ch n tr liu OAD mi tht bi, m k
c iu tr OAD kt hp cui cng cng tht bi

2220 bnh nhn i tho ng tp 2 iu tr vi MET + SU

Patients on SU + Metformin with HbA1c > 8%

100%
85%
Patients with HbA 1c >8%

79%
80%
68%
60%
44%
40%

20%

0%
First year Second year Third year Fourth year

Years after addition of SU to MET

Cook et al. Diabetes Care 2005; 28:995-1000

 ADOPT: Nng HbA1c tng
lin quan suy gim chc nng t bo
8.0
Annualised slope (95% CI)
7.6

7.2
Hb1Ac (%)

6.8

6.4

Rosiglitazone 0.07 (0.06 to 0.09)

6.0 Metformin 0.14 (0.13 to 0.16)*
Glibenclamide 0.24 (0.23 to 0.26)*
0
0 1 2 3 4 5

Number of subjects Nm
4,012 3,308 2,991 2,583 2,197 822

*C s khc bit c ngha gia nhm Rosiglitazone v cc nhm iu tr khc (sau hiu chnh Hochberg)

Kahn SE, et al. N Engl J Med. 2006; 355: 242743.

 Nguyn nhn suy gim chc nng t bo ty

hiu ng Khng insulin Di truyn

Incretin (TCF 7L2)

Lng ng
cht amyloid RL chc nng Tui
t bo ty

Nhim c Nhim c lipid

Glucose FFA
 Glycemic Recommendations for
Nonpregnant Adults with Diabetes
HbA1C <7.0%*
(<53 mmol/mol)

Preprandial capillary 80130 mg/dL*

plasma glucose (4.47.2 mmol/L)

Peak postprandial <180 mg/dL*

capillary plasma (<10.0 mmol/L)
glucose
* Goals should be individualized.
Postprandial glucose measurements should be made 12 hours
after the beginning of the meal.

American Diabetes Association Standards of Medical Care in Diabetes.

Glycemic targets. Diabetes Care 2016; 39 (Suppl. 1): S39-S46
 Nhp vin cp cu lin quan thuc bn > 65 tui

35,000 35%
Number of hospital admissions

Percentage of admissions
30,000 30%

25,000 25%

20,000 20%

15,000 15%

10,000 10%

5,000 5%

0 0%

Data given are number and percentage of annual national estimates of hospitalisations. Data from the NEISS-CADES
project.
ER visits n=265,802/Total cases n=12,666
Budnitz et al. N Engl J Med 2011;365:21
 c tnh s bnh nhn T gia nm 2000 v
2030 cc nc ang pht trin (v % thay i)

+247%

+308%

+189%

Wild, S et al.: Global prevalence of diabetes: Estimates for 2000 and

projections for 2030 Diabetes Care 2004 In press
Approach to the Management of Hyperglycemia

ADA. 6. Glycemic Targets. Diabetes Care 2015;38(suppl 1):S37. Figure 6.1; adapted with
permission from Inzucchi SE, et al. Diabetes Care, 2015;38:140-149
MC TIU KIM SOT GLUCOSE
MU CHO BNH NHN T
C NHN HA
ng thun kim sot ng mu cho bnh nhn T
ngi cao tui ( 65 tui) ca Hi i Tho ng Hoa
K v Hi Lo Khoa Hoa K nm 2016
c im ngi bnh HbA1C ng mu ng mu
T cao tui ( 65 cho php i hoc trc trc khi i
tui) n (mg/dL) ng (mg/dL)
Khng bnh phi hp , < 7.5% 90130 90150
sng lu, t nguy c,
minh mn
C bnh phi hp v sa < 8.0% 90150 100180
st tr tu mc nh
Nhiu bnh phi hp, < 8.5% 100180 110200
bnh tim mch nng,
nguy c h ng
huyt cao, sa st tr tu
nng
 Kim sot HbA1C km l hin tng
ph bin trn lm sng
ng u (n=2,605)
HbA1c < 7.0% HbA1c 7.0%

36.0
64.0 VIETNAM Thailand Singapore n
(Diabcare 2003) (Diab Registry2) (Diabcare3) (DEDICOM4)

Chu (n=5,376)
28.4 30.2 33.0 37.8
37.8
71.6 69.8 67.0 62.2
37.3
62.7 Hong Kong Trung Quc Hn Quc M
(Diab Registry5) (Diabcare6) (KNHANES7) (NHANES8)

Chu M Latin (n=1,712) 41.1 43.5 57.0

39.7
43.0
60.3 58.9 56.5
36.0
64.0
1. Bryant W, et al. MJA 2006;185:305309. 2. Kosachunhanun N, et al. J Med Assoc Thai 2006;89:S66S71.
3. Lee WRW, et al. Singapore Med J 2001;42:501507. 4. Nagpal J & Bhartia A. Diabetes Care 2006;29:23412348.
5. Tong PCY, et al. Diab Res Clin Pract 2008;82:346352. 6. Pan C, et al. Curr Med Res Opin 2009;25:3945.
7. Choi YJ, et al. Diabetes Care 2009;32:20162020. 8. Cheung BMY, et al. Am J Med 2009;122:443453.
 Chc nng t bo beta suy gim
chin lc iu tr cn thay i
FBG t mc tiu
Basal-bolus (ton phn)
HbA1c > HbA1c mc tiu

Thm nsulin nhanh trc 3 ba n

FBG t mc tiu

HbA1c > HbA1c mc tiu Basal-plus ( bn phn)

FBG > FBG mc tiu

Thm insulin nhanh trc ba n chnh
HbA1c > HbA1c mc tiu
Basal . Thm insulin nn v chnh liu

Thay i li sng + metformin ( thuc vin khc)

Suy gim chc nng t bo beta tin trin

Raccah D, et al. Diabetes Metab Res Rev 2007;23:25764.
 WHAT!?
Did you say
INSULIN?!

Ro cn x dng
insulin cho bnh
nhn T tp 2
 Ro cn thng gp khi iu tr Insulin
cho bnh nhn i tho ng tp 2

Pha bnh nhn T Bc s

Cm ngh bnh nng, Khng ch
tht bi iu tr. S dng insulin phc
S dng insulin phc tp
tp S h ng huyt
S h ng huyt S tng cn
S tng cn Khng c thuc..
S kim, s tim Nhiu kin cn
Xu h khi tim tham kho thm.
insulin m ng
Ross SA et al. Curr Med Res Opin. 2011;27 Suppl 3:13-20.
2.Vai tr insulin analogue trong
kim sot ng mu trong
bnh i tho ng tp 2
 1922 Banting and Best use bovine insulin extract on
human
1996 Lilly Humalog "insulin lispro INN" approved by
the U.S. Food and Drug Administration
2003 Aventis Lantus "glargine" insulin analogue
approved in USA [20]
2004 Sanofi Aventis Apidra insulin "glulisine"
analogue approved in the USA.
2006 Novo Nordisk's Levemir "insulin detemir INN"
analogue approved in the USA-
2007 Novo Nordisk created "aspart" and marketed it
as NovoLog/NovoRapid (UK-CAN) as a rapid acting
insulin analogue
 Thi gian
Action tc dng
Profiles ca cc loi insulin
of Insulins
Aspart, glulisine, lispro 45 hours
Plasma Regular 68 hours
insulin NPH 1216 hours
levels
Detemir ~14 hours
Ultralente 1820 hours
Glargine ~24 hours

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24
Hours
Burge MR, Schade DS. Endocrinol Metab Clin North Am. 1997;26:575-598; Barlocco D. Curr Opin Invest
Drugs. 2003;4:1240-1244; Danne T et al. Diabetes Care. 2003;26:3087-3092
 Serum concentration and half-life of insulin
degludec and insulin glargine
IDeg 0.8 U/kg
IGlar 0.8 U/kg
Insulin concentration

T1D - IGlar, insulin glargine

(% of maximum)

Time since injection (hours)

IDeg IGlar

0.4 U/kg 0.6 U/kg 0.8 U/kg 0.4 U/kg 0.6 U/kg 0.8 U/kg

Half-life (hours) 25.9 27.0 23.9 11.8 14.0 11.9

Mean half-life 25.4 12.5

Heise et al. IDF 2011:P-1444; Diabetologia 2011;54(Suppl. 1):S425; Diabetes 2011;60(Suppl. 1A):LB11
BM INSULIN (INSULIN PUMP)

32
 H THNG CUNG CP INSULIN QUA DA
Transdermal Insulin Drug Delivery (TDD) System

Dng sng siu m

a insulin vo
c th qua:
- Nang lng
- L m hi
INSULIN HT
Exubera Pfizer FDA 1.2006

34
 Slide 35

3.Liu php insulin nn

Cho bnh nhn TTp 2
Tit insulin sinh l hng ngy
 Liu php insulin nn v insulin tng cng
Basal insulin
Suppresses glucose production between
meals and overnight
Nearly constant levels
50% of daily needs
Ideally, for insulin-replacement therapy, each
component should come from a different insulin
with a specific profile
 Slide 38

v c th bt u insulin nn vo bt
k thi im no
V kinh in, insulin dnh cho bc iu tr cui
cng
tuy nhin, cn nhc li ch ca n nh ng
huyt, insulin c th bt u sm hn v ngay
khi c th

KHNG KiM
+ 1 LoI + 2 LoI + 3 LoI
SOT C
BNG LI SNG THUC VIN THUC VIN THUC VIN

BT U INSULIN NN
 Healthy eating, weight control, increased physical activity & diabetes education
Mono-
therapy Metformin
Efficacy* high
Hypo risk low risk
Weight neutral/loss
Side effects GI / lactic acidosis
MetforminCosts low

intolerance or If HbA1c target not achieved after ~3 months of monotherapy, proceed to 2-drug combination (order not meant to denote
any specific preference - choice dependent on a variety of patient- & disease-specific factors):
contraindication Metformin Metformin Metformin Metformin Metformin Metformin
+ + + + + +
Dual Sulfonylurea Thiazolidine- DPP-4 SGLT2 GLP-1 receptor Insulin (basal)
therapy dione inhibitor inhibitor agonist
Efficacy* high high intermediate intermediate high highest
Hypo risk moderate risk low risk low risk low risk low risk high risk
HbA1c Weight gain gain neutral loss loss gain
9% Side effects hypoglycemia edema, HF, fxs rare GU, dehydration GI hypoglycemia
Costs low low high high high variable

If HbA1c target not achieved after ~3 months of dual therapy, proceed to 3-drug combination (order not meant to denote
any specific preference - choice dependent on a variety of patient- & disease-specific factors):
Metformin Metformin Metformin Metformin Metformin Metformin
+ + + + + +
Triple Sulfonylurea Thiazolidine-
dione
DPP-4
Inhibitor
SGLT-2
Inhibitor
GLP-1 receptor
agonist
Insulin (basal)
therapy + + + + + +
TZD SU SU SU SU TZD

or DPP-4-i or DPP-4-i or TZD or TZD or TZD or DPP-4-i

or SGLT2-i or SGLT2-i or SGLT2-i or DPP-4-i or Insulin or SGLT2-i

Uncontrolled or GLP-1-RA or GLP-1-RA or Insulin or Insulin or GLP-1-RA

hyperglycemia or or Insulin
Insulin
(catabolic features,
BG 300-350 mg/dl,
If HbA1c target not achieved after ~3 months of triple therapy and patient (1) on oral combination, move to injectables, (2) on GLP-1 RA, add
HbA1c 10-12%) basal insulin, or (3) on optimally titrated basal insulin, add GLP-1-RA or mealtime insulin. In refractory patients consider adding TZD or SGL T2-i:
Metformin
+
Combination
injectable Basal Insulin + Mealtime Insulin or GLP-1-RA
therapy
Diabetes Care 2015;38:140-149; Diabetologia 2015;58:429-442
 Insulin nn + thuc vin

Thuc vin ung vo

ban ngy

8pm 2am 8am 2pm 8pm 2am 8am

Tim insulin
nn (vo bui
ti)
T lm gim H i s gim H sut 24 gi

Insulin nn
Thuc vin
Plasma glucose (mg/dl)

Ngi bnh thng

Ba n Ba n Ba n

Time of day (hours)

Polonsky K et al. N Engl J Med 1988;318:12311239

Liu lng theo thi gian insulin nn
i vi liu 1 ln/ngy

Xt nghim H
vo bui sng
Liu insulin
trc lc ng

Das et al. JAPI 2009 http://www.japi.org/february_2009/premix_insulin.html

Chun liu insulin nn
Meneghini v cng s (3-0-3) cch chnh liu

Chun liu da vo tr s trung bnh ca H trong 3 ngy trc khi chun

Pre-prandial blood glucose value Basal insulin

dose adjustment
mmol/L mg/dL Units

< 4.4 < 80 -3

4.4-6.1 80-110 No adjustment

> 6.1 > 110 +3

Bt k cn h ng huyt no nn c xem xt trc khi chun

Meneghini L et al. DOM 2007;9:902-13

Hiu chnh insulin nn da vo ng huyt vo bui sng
(NPH bui ti) theo Unnikrishnan v cng s (2009)

Glucose mu i bui sng Liu insulin hiu chnh

mmol/l mg/dl UI insulin
< 4,4 < 80 -2 U
4,4- 6,1 80-110 Khng thay i
6,2-7,8 111-140 +2 U
7,8 140 +4 U
 Hiu chnh liu insulin nn theo AACE,
ADA/EASD (2012)
ADA/EASD AACE
Liu bt u khi:
HbA1c : 7-< 8% 0,1-0,2 U/kg 0,1-0,2 U/kg
HbA1c : 8% 0,3-0,4 U/kg 0,2-0,3 U/kg
(Glucose tng cao)
Mc tiu ng mu Lc i/trc n : Lc i/trc
<130 mg/dl ba n <110
Trc khi i ng mg/dl
<180 mg/dl
Lch trnh iu chnh Tng 1-2 U / 2 ln Tng 2 U/ 2-3
liu mi tun ngy
T l BN t HbA1c<7% sau khi thm
Insulin nn
100 2312 BN iu tr 6 thng bng Insulin analogue tc dng ko di
90
75.4%
80
% Bnh nhn
70 62.8%
60 55.8%
46.5%
50
40 33.9%
30
20
10
0
Baseline HbA1c <8.0 8.0-8.4 8.5-8.9 9.0-9.4 >9.4
n 581 436 360 327 608
Mean BL HbA1c 7.56 8.19 8.69 9.20 10.19

Riddle MC et al Diabetes 2009; 58(Suppl 1):A125

Khuyn co s dng insulin nn
Gio dc bnh nhn ti thi im
s dng insulin u tin

- K thut v v tr chch Insulin

- Bo qun Insulin, qu trnh i li v ti
trng hc
- Nhn bit v iu tr h glucose mu
- Nguyn tc s dng liu insulin c bit lin
quan tp th dc.
- Ch tit thc tm quan trng thi gian n
v n dm
- Hng dn nhng ngy b m
 Slide 50

Dc ng hc
cc loi insulin tc dng ko di

c tnh (gi)
Khi u nh tc
Loi insulin Tn insulin
tc dng dng
Insulin ngi tc dng trung bnh Insulatard 1.5 4 4 - 10

Humulin N 1.5 4 4 - 10

Insulin analogue tc dng di Insulin Detemir (Levemir) 1-3

Insulin Glargine (Lantus) 1-3

Adapted from Mooradian et al. Ann Intern Med 2006; 145: 125-34
Idealized Profiles of Human Insulin
and Insulin Analogs
Rapid-acting: lispro, aspart, glulisine

Regular insulin
NPH

Insulin detemir
Plasma Insulin
Concentration Insulin glargine

0:00 2:00 4:00 6:00 8:00 10:00 12:00 14:00 16:00 18:00 20:00 22:00 24:00

Time

Rosenstock J. Goldstein BJ et al, eds. Textbook of Type 2 Diabetes. Martin Dunitz;2003:131-154.

Plank J et al. Diabetes Care. 2005;28:1107-1112.
Glargine vs NPH Insulin in Diabetic patients
Action Profiles by Glucose Clamp

6
NPH
Glucose utilization rate

5
Glargine
4
(mg/kg/h)

0
0 10 20 30
Time (h) after SC injection
End of observation period

Lepore, et al. Diabetes. 1999;48(suppl 1):A97.

So snh bin c h glucose mu
gia Insulin Analogue v NPH
Events per patient exposureyear

1.4 *
1.2
* NPH
* Insulin glargine
*
1.0 *
Basal *
0.8
insulin
0.6 *

0.4

0.2
Breakfast Lunch Dinner
0
20 22 24 2 4 6 8 10 12 14 16 18
Time of day (h)
Hypoglycaemia defined as plasma glucose 72 mg/dL
*P<0.05 vs insulin glargine
Adapted from Riddle M, et al. Diabetes Care. 2003;26:3080-3086. Used with permission.
Bin php khc phc hiu ng Somogyi

Khng tng insulin liu vo bui chiu

Kim tra ng mu mao mch lc 3 gi
sng xc nh h ng huyt
Cn ba n ph bui ti.
Gim liu insulin nn
Thay NPH bng nhm Analogue chm
Hin tng Down
56
 Hin tng Dawn

L s gia tng ng huyt bui sng .

Do cc hormone (GH,Cortisol,Cathecholamine)
tc ng gan lm phng thch mt s lng ng
vo mu.
C th bnh nhn phng thch insulin kim sot
s tng ng mu ny nhng khng insulin
Tng liu insulin nn vo bui ti theo khuyn
co.
 Bin chng v hu qu
ca h ng huyt
Mc ng huyt

110
6

100

5 90

80 Tng nguy c Thiu glucose no

4
70 lon nhp tim1 t t2
60

Suy gim nhn thc

3
50 Ko di bt thng
40 thi gian ti cc tim Hnh vi bt thng
QTc v QTd
2
30
ng kinh
1 20
t t
mmol/L Hn m
10
Cht no
mg/dL

1. Landstedt-Hallin L et al. J Intern Med. 1999;246:299307.

58
2. Cryer PE. J Clin Invest. 2007;117(4):868870.
59
6
 Definition of Hypoglycemia
Low plasma glucose causing neuroglycopenia
Clinical definition of hypoglycaemia:
Mild: self-treated
Severe: requiring help for recovery
Biochemical definition of a low plasma glucose:
3.0 mmol/L (<54.1 mg/dL) (EMA)1
3.9 mmol/L (70 mg/dL) (ADA)2
4.0 mmol/L (<72 mg/dL) for clinical use in patients treated with
insulin or an insulin secretagogue (CDA)3
ADA, American Diabetes Association; CDA, Canadian Diabetes Association; EMA, European Medicines Agency
1. EMA. CPMP/EWP/1080/00. 2006; 2. ADA. Diabetes Care 2005;28:12459; 3. Yale et al. Canadian J Diabetes 26:2235
Gio dc bnh nhn ti thi im
s dng insulin u tin
Tho lun vi BN c bnh thn mn v nguy c h
ng huyt do ko di tc dng insulin khi b suy thn.
2013 Novo Nordisk's Tresiba "insulin degludec INN" analogue
approved in Europe (EMA with additional monitoring]
Designing insulin degludec: structure

Jonassen et al., Pharm Res 2012 Published online April 2012 DOI 10.1007/s11095-012-0739-z
Liu php insulin tng cng
 Insulin tit sinh l trong cc ba n

75
Breakfast Lunch Dinner
Plasma insulin (U/ml)

50

25

4:00 8:00 12:00 16:00 20:00 24:00 4:00 8:00

Time
 Liu php insulin tng cng
Bolus insulin (mealtime or prandial)
Limits hyperglycemia after meals
Immediate rise and sharp peak at 1 hour
10% to 20% of total daily insulin requirement
at each meal
Ideally, for insulin-replacement therapy, each
component should come from a different insulin
with a specific profile
 #
Figure 3. Injections Complexity
Basal Insulin
Approach 1 (usually with metformin +/- low
other non-insulin agent)
to starting
& adjusting Start: 10U/day or 0.1-0.2 U/kg/day
Adjust: 10-15% or 2-4 U once-twice weekly to
insulin in reach FBG target.
For hypo: Determine & address cause;
T2DM dose by 4 units or 10-20%.

If not
controlled after
FBG target is reached
(or if dose > 0.5 U/kg/day),
treat PPG excursions with
meal-time insulin.
(Consider initial
Add 1 rapid insulin* injections GLP-1-RA Change to
2 mod.
before largest meal trial.) premixed insulin* twice daily

Start: 4U, 0.1 U/kg, or 10% basal dose. If Start: Divide current basal dose into 2/3 AM,
A1c<8%, consider basal by same amount. 1/3 PM or 1/2 AM, 1/2 PM.
Adjust: dose by 1-2 U or 10-15% once- Adjust: dose by 1-2 U or 10-15% once-
twice weekly until SMBG target reached. twice weekly until SMBG target reached.
For hypo: Determine and address cause; For hypo: Determine and address cause;
corresponding dose by 2-4 U or 10-20%. corresponding dose by 2-4 U or 10-20%.

If not If not
controlled, Add 2 rapid insulin* injections controlled,
3+ consider basal-
before meals ('basal-bolus) consider basal- high
bolus. bolus.
Start: 4U, 0.1 U/kg, or 10% basal dose/meal. If
A1c<8%, consider basal by same amount.
Adjust: dose by 1-2 U or 10-15% once-twice
weekly to achieve SMBG target.
For hypo: Determine and address cause;
corresponding dose by 2-4 U or 10-20%.

Diabetes Care 2015;38:140-149;

Diabetologia 2015;58:429-442 Flexibility more flexible less flexible
 Bc 2 : 0 - 0 - RA - G

Add 0.1 U/kg RA before largest meal, increase dose

until pre-BT target is reached or 0.2 U/kg for RA
RA levemir
Serum insulin (mU/L)

50

40

30
RA
20 SMBG SMBG SMBG

10
levemir
0
0 2 4 6 8 10 12 14 16 18 20 22 24
Hours
 Nn + 1 nhanh vs insulin hai pha (premix)

2 MI TIM , 2 BT 1 MI TIM , 1 BT

Thuc vin ung

8pm 2am 8am 2pm 8pm 2am 8am

Insulin nn
+ Insulin nhanh Insulin trn sn
trc n (vo bui ti)
(vo bui ti)
 Bc 3 : RA - 0 - RA - G

Add 0.1 U/kg RA before next largest meal, increase dose

until 2 hours post meal target is reached or 0.2 U/kg for RA

RA RA levemir
Serum insulin (mU/L)

50

40

30
RA RA
20 SMBG SMBG SMBG SMBG

10
levemir
0
0 2 4 6 8 10 12 14 16 18 20 22 24
Hours
 Quy c dung Insulin phi hp giai
oan 2
R/N-0-R/N-0 hoc RA/N-0-RA/N-0

R/N R/N
Serum insulin (mU/L)

Overinsulinization
50
Overinsulinization
40 Overinsulinization

30
SMBG SMBG SMBG SMBG SMBG
20 Reg Reg

10
NPH NPH
0
0 2 4 6 8 10 12 14 16 18 20 22 24

Thi gian (Hours)

Additional SMBG required to differentiate relative versus absolute hypoglycemia
Liu lng theo thi gian Insulin 2 pha
i vi liu 1 ln/ngy

Nu H ban m
cao hn Liu insulin vi ba
n sng chnh

Nu H bui sng
cao hn Liu insulin vi ba
n chiu chnh

Das et al. JAPI 2009 http://www.japi.org/february_2009/premix_insulin.html

Chun liu insulin
Unnikrishnan v cng s - Phng php
chun liu

Chun liu da vo tr s h thp nht ca bt k 3 ngy trc khi chun

Pre-prandial blood glucose value Premix insulin

dose adjustment
mmol/L mg/dL Units
< 4.4 < 80 -2
4.4-6.1 80-110 No adjustment
6.2-7.8 111-140 +2
>7.8 >140 +4

Bt k cn h ng huyt no
nn xem xt trc khi chun liu

Unnikrishnan et al. IJCP 2009: 63(11):1571-7,

Expert Opinion, BDI Advisory Group Jun 5-6, 2012
 Liu php insulin tch cc
3 phng /nn (Basal bolus)
 Bc sau cung : RA - RA - RA - G

Add 0.1 U/kg RA before mid-day meal, increase dose

until post meal target is reached or total daily dose reaches 1.5 U/kg
Consider additional injection of RA for snacks

RA RA RA levemir
Serum insulin (mU/L)

50

40

30
RA RA
20 SMBG SMBGRA SMBG SMBG

10
levemir
Glargine
0
0 2 4 6 8 10 12 14 16 18 20 22 24

Hours
Cc chin lc iu tr insulin tng cng
trong T tp 2
Bnh tin trin Cn tng liu kim sot H sau n

1 mi 2 mi 3 mi
1 bt 1 bt 1 bt

Khi u PreMix 2 PreMix 3

PreMix 1 ln mi ngy ln mi ngy
ln mi ngy

Khi u insulin
nn
iu tr nhiu iu tr nhiu
PHC
miTP
timHAY KHNG TH
miCHP THUN
tim nn
1 ln mi ngy
Nn- nhanh phng

1 mi 1 +1 mi 1 + 2/3 mi
2 bt 2 bt
 Khuyn co s dng
liu php insulin tng cng
 Thun li
- Kim sot ng huyt c c s hn vi
kh nng chn liu insulin theo s thay i
ch tit thc, hot ng th lc v au m
- Tr hon s khi u v s tin trin ca :
bnh vng mc, bnh thn (protein niu v
microalbumin niu), bnh thn kinh, bnh vi
mch
- Gim nguy c ca RLLP mu
- Ci thin s thoi mi
- Gim t vong m v thai nhi trong thai k
Chn insulin nhanh Insulin analog
Bt u tc dng : 5 pht
Insulin Insulin analog
(Glulisine-Aspart-Lispro) nh : 1 gi
sinh l
Ko di : 3 gi

Insulin ngi

Nhc im insulin ngi:

Khng ging tit insulin sinh l

Tng ng huyt sau n

H ng huyt xa ba n

Phi tim trc ba n 30 pht

 Slide 83

Dc ng hc
cc loi insulin nhanh v hn hp
c tnh

Khi u nh tc
Loi insulin Tn insulin
tc dng dng

Insulin analogue tc dng ngn Insulin Aspart (NovoRapid) 0.2 0.5 0.5 - 2

Insulin Lispro (HumaLog) 0.2 0.5 0.5 - 2

Insulin Gluisine (Apidra) 0.2 0.5 0.5 - 2

Insulin ngi tc dng nhanh ActRapid 0.5 1 0.5 - 1

Humulin R 0.5 1 0.5 - 1

Insulin analogue pha sn Insulin Aspart (NovoMix) 0.2 0.5 1-4

Insulin NPL (HumaLog) 0.2 0.5 1-4

Insulin ngi pha sn Mixtard 0.5 1 3 - 12

Humulin Mix 0.5 1 3 - 12

Adapted from Mooradian et al. Ann Intern Med 2006; 145: 125-34
Insulin Analogs
Glulisine and Aspart Plasma Insulin Profiles

400 500
Plasma insulin (pmol/L)

Plasma insulin (pmol/L)

350 Regular 450 Regular
Glulisine 400 Aspart
300
350
250 300
200 250
150 200
150
100
100
50 50
0 0
0 30 60 90 120 150 180 210 240 0 50 100 150 200 250 300
Time (min) Time (min)
Meal Meal
SC injection SC injection

Heinemann, et al. Diabet Med. 1996;13:625629; Mudaliar, et al. Diabetes Care.

1999;22:15011506.
Bo qun insulin

Bo qun Thng tin thm

Bt tim Nhit phng Hp ng Insulin c
insulin ang (ti a khong th gip gi insulin
s dng 25C) mt trong thi tit
trong 46 tun nng
Insulin d Gi trong t Nn ly insulin ra
tr lnh, khong 4 khi t lnh t nht
8C. 30 pht trc khi
Khng ngn tim
Lun kim hn
dng trc khi tim
Insulin nn xa tr em
Royal College of Nursing. http://www.rcn.org.uk/publications/pdf/
Starting%20insulin%20in%20adults%20with%20type%202%20diabetes.pdf, 2005
CHN BM TIM INSULIN

86
 Thiu liu lng thuc chch vo
trnh bt kh trong ng tim, bnh
nhn thng cho ra ngoi 1 hoc 2 git
thuc trc khi tim Trc y 1 git
Insulin ch cha (20 git = 40 UI
Insulin/ml) 2 UI
Hnh thc ng gi mi ny 1 git ( 20
git = 100 UI insulin/ml) cha 5 UI
Insulin. Nh vy s lng thuc b tht
thot nhiu.
Gim cht lng l thuc
Do a kim tim vo l thuc 1000
UI, trung bnh 100 ln ( ln 10 UI)
nguy c cao v h thuc ( thuc
thay i mu hoc vn c..)
 Nhim trng
Mi ln chch nhu cu bnh nhn trung
bnh ch 10 UI
S dng ht l thuc s ln a kim
vo np cao su trung bnh 100 ln
Nguy c nhim trng cao do t cu v
lin cu ti ch chch vi nguy c hoi
t v teo t chc da.
Thit b bt tim so vi ng tim

Bt tim ng tim
Kn o Khng

Mang theo d dng Khng

Liu chnh xc Li liu ph bin (trn)

D s dng Kh s dng

o to t o to nhiu hn

n gin Phng php phc tp

K thut tim
C 4 bc
1. m kim ~90
2. n nt tim insulin
3. Gi kim tim ti ch tim v m n s 7
4. Ly kim ra

Nu cn, vo da khi tim:

Cch vo da khi tim ng Vo da gia ngn ci v 2
ngn tay
m kim vo
Gi np da
Tim insulin
Gi nguyn v tr kim tim
Correct Incorrect Needle ti ch tim m n s 7
insertion Bung np vo da ra
Rt kim ra

http://www.bddiabetes.com/us/pdf/injection_techniques_bd_pen_needles.pdf, 2005
Royal College of Nursing. http://www.rcn.org.uk/publications/pdf/
Starting%20insulin%20in%20adults%20with%20type%202%20diabetes.pdf, 2005
Injection Technique

2004 BD
 V tr chch insulin
Where to inject :
Abdomen
Thigh (upper & side)
Backside
Under upper arm
(loose skin)

93
 T l phn b
cc v tr LMDDB dy nht trn SA

%
2.6
1

2 4.33

3 11.94
4 26.84 39.83
5

6 11.26
7 2.1
8 1.1

0 5 10 15 20 25 30 35 40
 SlametS

Nguy c h ng huyt sau n

Lit d dy (Gastroparesis)

97
 Nguy c h ng huyt
Bnh thn T giai on cui
 2014
Ashfield Healthcare
Communications

- Tng nhng cn h ng huyt nng

- H ng huyt khng nhn bit
- Tng cn
- Bc pht thong qua bnh vng mc
(him tr em)
- Tng thi gian, n lc, chi ph
- Bnh nhn dng bm insulin, tang nhim
toan, v nhim khun v tr truyn
- t thch hp cho tr <7 tui
ng thun kim sot ng mu cho bnh nhn T
ngi cao tui ( 65 tui) ca Hi i Tho ng Hoa
K v Hi Lo Khoa Hoa K nm 2016
c im ngi bnh HbA1C ng mu ng mu
T cao tui ( 65 cho php i hoc trc trc khi i
tui) n (mg/dL) ng (mg/dL)
Khng bnh phi hp , < 7.5% 90130 90150
sng lu, t nguy c,
minh mn
C bnh phi hp v sa < 8.0% 90150 100180
st tr tu mc nh
Nhiu bnh phi hp, < 8.5% 100180 110200
bnh tim mch nng,
nguy c h ng
huyt cao, sa st tr tu
nng
Khuyn co liu insulin nhanh ( plus/bolus)
trc n cho bnh nhn T tp 2 ?
 1. D nh chch insulin cho ba n no
(sng, tra, ti) chn t
insulin/carbohydrate choice

2. Loi insulin dng human hay analogue

3. Lng thc n cha cht ng s

tiu th trong ba n (k c lng cht
x cha cht ng)
 4. Chn t CHO/insulin (dnh cho lng
CHO d kin s s dng, ph thuc ba n
v ngi bo gy)
Trung bnh 1 UI insulin cho 1 CHO choice
(10 -15 gam CHO ty thi im ba n, th
trng bo gy)
 Thc hnh ty Carb/Insulin

Bnh nhn nng di 70 kg:

Example: 60 grams = 4 UI insulin
15
Bnh nhn nng trn 70 kg
Example: 60 grams = 6 UI insulin
10

104
 5. Kim tra ng mu trc n ca mi
chch iu chnh liu insulin ph hp
hn.
6. Ch s ISF : iu chnh insulin khi ng
mu trc n cao hoc thp hn mc tiu
bnh thng ( 1 UI insulin c th gim glucose
huyt tng 30-50 mg/dl ty theo loi insulin
human hay analogue)
7 .Tng liu insulin s dng trong ngy tnh
ISF.
8. Tng liu CHO s dng trong ngy tnh
ISF.
 CACH TINH YU T NHAY INSULIN (ISF)
D oan nng glucose mg/dl gim cho 1 UI insulin
Cng thc ISF = S Rules/tng liu insulin trong ngy

Quy nh y t dung Rules tinh ISF.

1500 Rules dnh cho insulin tac dng ngn
(Insulin regular)
1800 Rules i vi insulin tac dng nhanh (Insulin
analogue).
 9. D nh n ba ph sau chch (thi gian
v s lng carbohydrate)

10.Hnh thc tp luyn th lc sau ba n

c th gy h ng huyt ( b sung CHO
trong qu trnh tp luyn)
 Hng dn th dc 1

Loi th dc Nu glucose mu Tng CHO ngh thc

phm
Thi gian ngn hoc < 80-100 mg/dl 10-15 grams. 1 fruit or 1 bread
cng trung bnh 100 mg/dl Not necessary ___

Cng trung bnh < 80 mg/dl 25-50 grams before meat sandwich +
exercise then 10-15 milk or fruit
grams/hr, if
necessary
80-170 mg/dl 10-15 grams 1 fruit or 1 bread
180-300 mg/dl Not necessary ___
300 mg/dl Dont exercise ___

Hot ng mnh < 80 mg/dl 50 grams 1 meat sandwich +

hoc tp th dc milk or fruit
180-300 mg/dl 10-15 grams/hr 1 fruit or 1 bread
300 mg/dl Dont exercise ___

110
 11.Chc nng thn ( 25% insulin thi qua
thn hng ngy ) nhm gim liu insulin
ngi hn insulin analogue.

12.Bnh l d dy T (Gastroparesis) nhm

chn thi im chch insulin nhanh cho
tng ba n trnh h ng huyt ngay sau
n .

 SlametS

Lit d dy
(Gastroparesis)

112
RECEPTOR BINDING, METABOLIC AND
MITOGENIC POTENCY OF IA
 Slide 115

Kt lun
Insulin vn l thuc h ng huyt hiu
qu nht v hu ht bnh nhn i tho
ng tp 2 u cn insulin trong giai on
no
Ngy nay iu tr insulin sm t mc
tiu ng huyt c khuyn co
Bt u v la chn insulin hin nay ty
thuc vo tng bnh nhn
S dng insulin analogue an ton v hiu
qu hn so vi insulin thng quy trong kim
sot ng huyt ph hp vi tng bnh
nhn.
 Kt lun
Liu php insulin cho bnh nhn T tp 2 c
hiu qu l mt s hp tc tt gia
Thy thuc , iu dng, Bnh nhn v Thn nhn

Bn cnh can thip li sng, dinh dng, s dng

hp l insulin v phng tin theo di ng
huyt. S dng insulin kim sot ng huyt
cn ch c nhn ha
Chn thnh cm n s theo di ca
Qu ng Nghip
 Knh mi qu ng nghip tham d
Hi Ngh i Tho ng-Ni Tit-Ri Lon Chuyn
Ha Min Trung-Ty Nguyn M Rng ln X
Ti Bun M Thut (9-10/12/2016)
 Lm th no xc nh liu insulin
trc n cho bnh nhn T tp 2 ?
BN nam 55 tui, T typ 2 a 10 nm. Hin s dung liu phap
insulin phong nn (bolus-basal) vi 34 UI.insulin analogue
Ba n tra nay d kin 15
15
15 17 grapes

1 cup coffee
w/ 3 sugar packets 0
3 oz salmon 1 cup french fries
Coffee w/ sugar 15 grams
Salmon 0 grams
French fries 15 grams 15
Cabbage 15 grams
Grapes + 15 grams

1 cups cooked red cabbage

TOTAL = 60 g carbs
Glucose trc n tra = 226 mg/dl Liu insulin phng
Muc tiu glucose mau oi = 100 mg/dl tra l ?
Cas LS 1 : Xac inh liu insulin trc n
Tng liu insulin= 34 units
Muc tiu glucose oi = 100 mg/dl
Nng glucose trc n = 226 mg/dl
Insulin:carbohydrate ratio : 500 34 = 14.7. Ratio= 1:15
Lng glucose d kin tiu thu 60 grams
ISF = 1800 34 = 52.9 (khoang 53)
Khac bit glucose gia muc tiu va hin tai = 226 100 =126
mg/dl
Lng insulin lam giam glucose trc n = 126 53 = 2.3 units

Tra li : liu insulin trc n

Lng insulin kim soat carbohydrates = 60 15 = 4 units
Insulin trc n = 2.3 units + 4 units = 6.3 units
122
 Bnh an s 2

BN n 56 tui, T typ 2 a 10 nm . Hin ang dung liu phap

insulin plus-basal (nn va 1 mui phong vao bui tra).
Tra nay khu phn n d kin 40 g CHO
Nng glucose trc n tra = 57 mg/dl
Nng glucose lc i theo muc tiu = 110 mg/dl
Ty Insulin: CHO=1:13 va ISF (Insulin Sensitivity Factor)=35
Y kin quy ng nghip trong tinh hung nay

A: Tng lng CHO ba n tra

B: Giam liu insulin trc n tra

C: Tri hoan gi chich insulin trc n tra

123
Cas LS 2 : Kim soat ha glucose trc n
Ty Insulin:carbohydrate = 1:13 va ISF = 35
60 grams of carbohydrate se tiu thu
Nong glucose trc n = 57 mg/dl
Nng glucose theo muc tiu = 110 mg/dl

ap an #1: Tng lng carbohydrate

1 grams of carbohydrate se tng glucose mau 35mg/dl
ap n # 2: Giam liu insulin trc n
Lng insulin kim soat carbohydrates= 60 13 = 4.5 units of insulin
Lng insulin d kin giam : Khac bit glucose muc tiu va hin tai ISF = 53
mg/dl 35 = 1.5 units insulin
Liu insulin trc n = 4.5 units 1.5 units = 3 units
ap an # 3: Tri hoan chich insulin trc n

1. Practical Carbohydrate Counting, American Diabetes Association, 2001

124