Download DM Rx. handout by Dr Sarma

Mandatory Examinations
1. Family H/o DM
1. Fasting and PP BG
2. H/o IHD. Angina, IC
2.
Hb A1c on Dx & six monthly
3. H/o Smoking
3.
Lipid profile, Lp(a), hs-CRP
4. H/o Hypoglycemia
4.
CHD Risk factors
5. Exam for all pulses
5.
MAU - ACR
6. B.P recording
6.
ECG for LVH, IHD
7. Foot exam - Trophic
7.
Echo for LVD, LVH
8. PNP and ANP
8. Stress test in equivocal cases
9. Fungal Infect., Pruritus
9.
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Fundus exam for DR
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Diagnosis – O-GTT
75g of oral glucose – 2 hrs. after
DM
DM
126 mg%
200 mg%
IGT
140 mg%
IFG
100 mg%
Normal
Normal
PPGday
• FBGFPG
> 126 & PPBG > 200 - same
• RBG > 200 mg % on 2 occasions or
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Diagnosis - Practical Points
1. Do not label one a diabetic by glycosuria alone
For, one may have renal glycosuria
2. Benedict’s less accurate; shows any reducing substance.
Glucose oxidase test strips confirm glucosuria
3. Do not neglect urine test for acetone
4. Never base Dx on a single blood sugar test
5. O-GTT (2 sample) is the gold standard for Dx. of DM
6. HbA1c – Not for Dx. Follow up once in 3 to 6 months
7. Majority of diabetics are not symptomatic – so screen
One may present first time with complications – too late
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Correlation of MPG - HbA1c
HbA1C %
MPG mg%
5
100
Mean Plasma Glucose =
6
135
7
8
9
10
11
12
13
170
205
240
275
310
345
380
(35.6 x HbA1c %) – 77.3
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HbA1c =
(MPG mg% + 77.3) / 35.6
Diabetes Care
Vol.26 (S), P33, 2003
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Blood Sample – Practical Points
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The whole blood glucose is 15% higher
We need to estimate plasma glucose
Na F is to be used as the anti-coagulant
Centrifuge and separate plasma within 1 hour
For HbA1c – we need EDTA added blood –
HbA1c measurement – No fasting is required
C-Peptide or Serum Insulin – Only on fasting
Shouldn’t add any anti-coagulant for C peptide
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Stages of T2DM
Insulin Resistance
IR
Stage 1
1. Insulin Resistance
2. Hyper Insulinemia
3. Normal Glucose Tolerance
IR + ID
Insulin Deficiency
Stage 2
1. Insulin Resistance
2. Declining Insulin levels
3. Abnormal Glucose Tolerance
Stage 3
1. Insulin Resistance
2. Very low Insulin levels
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ID
3. Hyperglycemia round the clock
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What is new in Rx. of T2DM
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The step-care therapy is not advocated now.
Choice of OAD/Insulin to be individualized
Glycemic targets must be achieved quickly
Multiple therapies may be needed
A1c is the target now - within 6 months
Diet alone is not the option now - difficulties
Even prediabetes needs Rx. aggressively
Total metabolic control – not glycemia alone
Combination of OAD + Insulin, early insulin
Avoid hypoglycemia by proper drug choice
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Stage Based Management
Stage 1
Stage 2
Stage 3
Pre Diabetic State
N FBG, ↑ PPBG
↑ FBG, ↑ PPBG
Weight Reduction
Diet and Exercise
Diet and Exercise
Physical Activity
Metformin, -GI !!
Metformin
May be Metformin
SU, GLN
TZD, SU (↓ effect)
No drug app. FDA
TZD, RA insulin
Basal In, AM PM In.
7% per yr - DM
Amylinomimetics
Exenatide, Pramlin.
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Today’s Treatment Goals
Keeping HbA1c and FBG, PPBG with in limits
1.
2.
Exercise – Diet – Weight reduction
OHAs and Insulin
Correction of all metabolic abnormalities
1.
2.
Normalizing lipids, BP Goal < 130/80
Reducing Obesity and Waist Circumference
Prevention and Rx. of complications
1.
Macrovascular, 2. Microvascular, 3. Metabolic
Special emphasis on Prevention of CHD
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Complications of T2DM
•
Metabolic Complications
1. IR; Obesity, Lipids – ↑TG, ↓HDL, ↑ sLDL
2. Thrombogenic ( ↑PAI-1, ↑ fibrinogen) profile
•
Micro-vascular Complications
1. Diabetic Retinopathy (DR)
2. Diabetic Kidney Disease (DKD) – Nephropathy
3. Diabetic Neuropathy – DPN, DAN
•
Macro-vascular Complication
1. Coronary Artery Disease (CAD)
2. Stroke, CVD, TIA, HT
3. Peripheral Vascular Disease (PVD)
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Ticking Clock of T2DM
1. Micro-vascular Complications
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At the onset of hyperglycemia
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Control of hyperglycemia essential
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The A1c target of less than 7 must (A)
2. Macro-vascular Complication
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•
At the onset of insulin resistance
•
Blood pressure goal of 130/80 (B)
•
Control of lipid abnormalities (C)
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How to Identify IR ?
Features
Insulin Resistance
Insulin Deficiency
Hyperglycemia
↑ PPBG
↑ FBG
Obesity, ACN
Present
Usually absent
Abdominal adiposity
Present
Absent
Metabolic Abnormality
Met S Present
Met S Absent
Hypertension (130/80)
Usually a feature
May or may not be
Recent weight change
Increase
Weight loss
C peptide / Insulin
Increased
Decreased
Medicines
OAD – Met, TZD, RG
OAD - Met + SU + In
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How to treat Insulin Resistance ?
Diet, Exercise, TLC
Weight reduction, Waist reduction
ID
IR
Metformin – unmasks Insulin receptors
Insulin sensitizers – TZDs - PPARγ
Abolition of Glucotoxicity
Control of hypertension
Control of Metabolic abnormalities
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Major Classes of Medications
1. Drugs that sensitize the
body to insulin and/or
control HGO
TZD – Glitazones And
Metformin
2.
Drugs that stimulate the
pancreas to make more
insulin
Sulfonylureas and
Meglitinides
3.
Drugs that slow the
absorption of starches
-Glucosidase
Inhibitors – Acarbose,
Miglitol, Voglibose
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Timeline for Utilization of Therapies
Metformin, TZD, (-GI add on)
SU
Meglitinide
Lifestyle
Glucose
350
300
250
200
150
100
50
Insulin
Post Meal Glucose
Fasting Glucose
250
Relative
Function
200
Insulin Resistance
150
100
50
Insulin Level
At risk
for Diabetes
Beta cell failure
0
-10
-5
0
5
10
15
20
25
30
Years of Diabetes
© International Diabetes Center. From Kendall D, Bergenstal R.
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Efficacy of Monotherapy - OADs
Drug Class
FBG Reduction
↓ HbA1c
Metformin (BG)
60-70 mg%
1.5 %
Sulfonylureas (SU)
60-70 mg%
1.5 %
Glinides (GLT)
35-40 mg%
1.0 %
Gliazones (TZD)
30-40 mg%
1.0 %
Acarbose (-GI)
20-30 mg%
0.6 %
DeFronzo Annals of Internal Medicine 1999;131:281-303, Nathan N Engl J Med 2002; 347:1342-1349
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Summary of all effects of Rx.
Intervention
Diet
Exercise
Metformin
Sulfonylureas
Glitazones
Insulin
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Glycemia
Lipids
B.P.
B.V
Weight
+
+/+
+
+
++
+
+
+
+
+
+
+
+
+
++
++
+
No
No
No
↑
+
+
+
+
+
↑
No
↑↑
Diabetes Spectrum Vol. 5, # 3, 103-108
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Basis of Treatment Decisions
Dx. of T 2 DM (2 readings)
LIFE STYLE
Hb A1c < 9.0 %
Early Insulin +/- OAD
No IR Features
RF N / Abn.
Test Hb A1c %
IR Features +
CHF +/-
N FBG, ↑ PPBG
LFT N /↑
↑FBG, PPBG N
OAD = BG, SU, TZD, RG, AGI,
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Acute/ DKA
Hb A1c > 9.0 %
DM 5 yr / 5+ yrs
SU aller.
lipid
HT
↑FBG, ↑ PPBG
OAD + In. + Amy + Ex
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Treatment Algorithm
NEJM 355; 2478 23 December 7, 2006
Dx. of T 2 DM (2 readings)
HbA1c < 9%
TLC + Metformin 3 mon.
HbA1c < 7
Y
HbA1c > 9%
I+OAD
No
Add Basal Insulin
Add SU
3M
HbA1c < 7
Y
No
↑ Insulin + OAD
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3M
HbA1c < 7
Y
Add TZD
Add TZD
HbA1c < 7%
No
Basal Insulin
No
Y
Add SU 19
Insulin Preparations
Rapidity of Action
Ultra- rapid-action
Onset 10’ -20’ Peak 30 min
Short Acting
Onset 30’ to 60’, Peak 2 hr
Intermediate Acting (Human)
or Analog 1 -4 h, Peak 4 -10 h
Long Acting 1-3 No Peak 24 h
Mixtures (Human)1 h, P 3-12 h
Insulin preparation
Lispro (Humalog), Glulisin (Apidra)
Aspart (Novolog)
Regular (Human) Insulin
Humulin R, Novolin R
NPH (Human) Humulin N, Novolin N
Insulin Detemir (analog) - Levemir
Insulin Glargine (Lantus)
70/30 or 50/50 Humulin, 70/30 Novolin
Mixtures (Analog)
Onset 30’-1h, Peak 3-12 h
75/25 or 50/50 Humalog (NPL + Lispro)
70/30 Novolog neutral (Protamin + Aspart
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Three Types of Profiles
Patient Profile
Choice of Regimen
Choice of Insulin
↑ PPG, N FBG,
RA Insulin Pre Meal
Human Regular or
Lispro or Aspart
↑ FBG, Day time
Euglycemia
Bed time IA Insulin
+/- OAD
Insulin NPH or
Detemir
↑ FBG, ↑ PPG
‘Round the clock
hyperglycemia’
IA insulin BID or
LA Insulin HS + OAD
NPH Detemir BID
or 70:30 BID,
or Glargine HS
Annals of Internal Medicine Volume 145 • Number 2, July 2006
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How to prevention
Complications of Diabetes ?
1.
2.
3.
4.
5.
6.
7.
8.
9.
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Weight reduction, Exercise
Strict control hyperglycemia
Achieving lipid profile targets
Smoking cessation
Rx. of Hypertension with ACEi/ ARB
Low dose Aspirin therapy
Statin therapy for all T2DM
ACEi or ARB for all with MAU
Early detection and evaluation
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Take Home – A B C D E
•
A
•
B
•
•
•
C
D
E
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A1c – target of < 7%; Better 6%
Aspirin for all DM
ACEi or ARB for all DM
Blood Pressure target of 130/80
Blood Glucose monitoring
Cholesterol LDL <100, Statin for all DM
Diet modifications, Do not smoke
Exercise 45’ every day, Education on DM
Equivalent to having CAD is DM
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Issues
Previous Methods
New Practice Guide
T2DM Stages
No definite staging
IR (1)  IR+ID (2)  ID (3)
Diagnosis
Half hourly GTT or Just BS
2 sample O-GTT – Gold Standard
Insulin Resis.
Not given due emphasis
It takes the center stage
Follow Up
FBG or PPBG
HbA1c 3 monthly, Not FBG, PBG
Rx Paradigm
Diet  OAD  Insulin
[TLC+ Met]  other OAD  Insulin
Rx Decisions
Not tailored, Bl Sug. based
HbA1c based, All factors taken
1st line OAD
SU – Diabetes  Daonil
Metformin, ↑ TZD, SU limitations
Insulin use
Delayed until pt is burnt out
Early basal Insulin or intens. Insul
Focus on
Glycemic control alone
Total Metabolic control  A,B,C
Prescriptions
Limited to OAD and Insulin
Aspirin, Statin, ACEi + DM Rx.
Prevention
Was not the emphasis
Prevent DM & prevent complicati.
www.drsarma.in Not worried for  apoptosis
Emphasis
Preserve the  cell at all costs
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