In the Name of ALLAH, Ever Beneficent, Infinitely Merciful

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HOW TO DIAGNOSEHOW TO DIAGNOSEDIABETES?DIABETES?

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TREATMENT TARGETSTREATMENT TARGETS

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Efficacy of Monotherapy in Type 2 Diabetes

Agent HbA1c reduction %

Fasting glucose

Reduction (mg/dl)

Sulphonylurea 1.5 - 2.0 60 - 80

Metformin 1.5 - 2.0 60 - 80

Pioglitazone 0.6 - 1.9 50 - 80

Alpha Gucosidase inhibitor

0.5 - 1.0 20 - 30

Bonnie Kimmel, MD and Silvio E. Inzucchi, MD Clinical Diabetes 23:64-76, 200504/11/2304/11/23 77

Current FDA Approved

Combination Therapy Options in Type 2 Combination Additional

Lowering of HbA1c

Additional Lowering of FBG

(mg/dl)

SU + MTF 1.5 – 2.0 60 – 80

SU + TZD 1.0 – 1.5 40 – 60

MTF + TZD 0.6 – 0.8 20 – 40

SU + AGI 1.0 – 1.5 20 – 40

Bonnie Kimmel, MD and Silvio E. Inzucchi, MD Clinical Diabetes 23:64-76, 2005

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Mazze, Strock, Simonson, Kendall, Cuddihy, Bergenstal. SDM Quick Guide 5th Edition, International Diabetes Center, 2009

Staged DiabetesManagement at IDC

*

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Stages of Type 2 Diabetes—Stages of Type 2 Diabetes—UKPDSUKPDS

-C

ell

Funct

ion (

%)

PostprandialHyperglycemia

IGT Type 2DiabetesPhase I Type 2

DiabetesPhase II

Type 2 DiabetesPhase III

25

100

75

0

50

-12 -10 -6 -2 0 2 6 10 14

Years From Diagnosis

Lebovitz H. Diabetes Review. 1999;7:139.04/11/2304/11/23 1010

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Patient J.L., December 15, 1922 Februray 15, 1923

The Miracle of The Miracle of InsulinInsulin

04/11/23 13

Adapted from Stratton IM, et al. UKPDS 35. BMJ 2000; 321:405–412.

UKPDS: decreased risk of diabetes-related complications UKPDS: decreased risk of diabetes-related complications associated with a 1% decrease in A1Cassociated with a 1% decrease in A1C

UKPDS: decreased risk of diabetes-related complications UKPDS: decreased risk of diabetes-related complications associated with a 1% decrease in A1Cassociated with a 1% decrease in A1C

Per

cen

tag

e d

ecre

ase

in r

ela

tive

ris

k co

rres

po

nd

ing

to

a 1

% d

ecre

ase

in H

bA

1C

**

Any diabetes-related endpoint

21%

**

Diabetes-related death

21% **

All cause

mortality

14%*

Stroke

12%

**

Peripheral vascular disease†

43%

**

Myocardial infarction

14%

**

Micro-vascular disease

37%

**

Cataract extraction

19%

Observational analysis from UKPDS study data

†Lower extremity amputation or fatal peripheral vascular disease*P = 0.035; **P < 0.0001

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“The Magnificent Seven”

When should Insulin be used in When should Insulin be used in Type 2 diabetes mellitus?Type 2 diabetes mellitus?

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1. Type 2 diabetes not controlled with maximal doses of Oral Hypoglycaemic agents

What do you mean by maximal doses of OHAs?

Metformin 2500/3000mg a day

+

Glipizide 20mg/glibenclemide15-20mg/day

Gliciazide 320mg/ Glimepride 6-8mg/day

+

Rosiglitazone 8mg/ Pioglitazone 45mg/day

When should Insulin be used in When should Insulin be used in Type 2 diabetes mellitus?Type 2 diabetes mellitus?

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2. Type 2 diabetes during periods of physiological

stress (surgery, infection)

Continue OHAs simultaneously.

Stop metformin in case of severe infections or

impending reduction in renal perfusion

When should Insulin be used in When should Insulin be used in Type 2 diabetes mellitus?Type 2 diabetes mellitus?

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3. gestational diabetes

Metformin may be continued

Discontinue other medications

When should Insulin be used in When should Insulin be used in Type 2 diabetes mellitus?Type 2 diabetes mellitus?

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4. Use of parenteral nutrition

or high-caloric supplements

Indications of Insulin therapy?Indications of Insulin therapy?

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5. Diabetic ketoacidosis (DKA)/Hyperosmolar

hyperglycemic nonketotic syndrome (HHNS)

Indications of Insulin therapy?Indications of Insulin therapy?

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6. Progressive complications:

proliferative retinopathy/maculopathy, progressive or painful neuropathy

For rapid control and tighter adjustment

Indications of Insulin therapy?Indications of Insulin therapy?

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7. Chronic Renal Failure

For all above a creatinine of 4.0mg/dl

Cutoffs for other OHAs:-

Metformin: 1.5mg/dl

Glimeperide/Glibenclemide: 2.0mg/dl

Glipizide: 2.5mg/dl

Pioglitazone/Rosiglitazone: 4.0mg/dl

Indications of Insulin therapy?Indications of Insulin therapy?

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Normal PancreasNormal Pancreas

Insulin is released in response to varying blood glucose levels and hypoglycemia does not occur

Insu

lin E

ffec

t

Basal Insulin (~0.5-1.0 U/hr)

‘Bolus’ Insulin (Meal Associated)

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How does one classify the types of insulin?How does one classify the types of insulin?

Generally classified according to peak effect and duration of action

Rapid acting/lispro /aspart/glulisine

Short acting: regular.

Intermediate acting: NPH.

Long acting(basal) lantus. /levimer.

Premixed:(30/70), (50/50), (75/25)04/11/2304/11/23 2929

Re

lati

ve

Ins

ulin

Eff

ec

tR

ela

tiv

e In

su

lin E

ffe

ct

Time (Hours)

0 2 4 6 8 10 12 14 16

Long-Acting: Glargine (Lantus®)Detemir (Levemir®)

18 20

Intermediate: NPH (Humulin® N, Novolin® N)

Short-Acting: Regular (Humulin® R, Novolin® R)

Rapid-Acting: Lispro (Humalog®), Aspart (NovoLog®),Glulisine (Apidra®)

Insulin Time Action Curves

Bergenstal, “Effective insulin therapy,” International Textbook of Diabetes Mellitus vol 1. 3rd ed, Chichester NY, John Wiley and Sons, Inc., 2004:995-1015. 04/11/23 31

What are the types What are the types of insulin regimens?of insulin regimens?

• Premixed regimen

• Split mix regimen

• Basal bolus regime (multidose)

• Bedtime dosing alone (NPH/Lente/Glargine)

• Infusion

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Premixed insulinPremixed insulinAVAILABLE PREPRATIONSAVAILABLE PREPRATIONS • Premixed(30/70): Regular: 30 % NPH :

70%

• Premixed (50/50): lispro 50% NPL 50%

• Premixed Analogs Biphasic insulin aspart (30/70) 30% : Aspart 70% : protaminated aspart

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Basic Insulin Regimen: Basic Insulin Regimen: Split-Mixed Regimen or Split-Mixed Regimen or

PremixPremix

Regular

NPH

B DL HS B

Endogenous insulin

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Basic Insulin Regimen: Basic Insulin Regimen: Split-Mixed Regimen or Split-Mixed Regimen or

PremixPremix• Does not

mimic normal physiology

• Requires meal consistency

• Snacking may result in weight gain

• Hypo- and hyperglycemia

Regular

NPH

B DL HS B

Endogenous insulin

Hyperglycemia

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Insulin Therapy RegimensInsulin Therapy Regimens

Usual starting dose: 0.5-1.0 unit/kg/day

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Premixed insulinPremixed insulin

• Dose adjustment:

• The fasting sugar depends on the night dose of insulin • The post breakfast sugar depends on the

morning dose of insulin

• Rough calculation increase the insulin by one unit to reduce the sugars by 25mg/dl

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Self Monitoring is crucialSelf Monitoring is crucial

Glucometers

At least 6-8 times a week ideally

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Premixed insulinPremixed insulin Advantages • more accurate dosing

• lesser injections

• Pen devices administer premixed forms

Disadvantages • Fine tuning may not be possible

• Strict meal pattern

• Nocturnal hypoglycemia

• May need “diet changes for insulin” rather than “insulin changes for diet”

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TIMING OF INJECTIONTIMING OF INJECTION

• 70/30 30 MINUTES BEFORE BREAKFAST AND SUPPER

• NOVO MIX 70/30

• HUMALOG MIX 25/75 5—15 MINUTES

• BEFORE BREAKFAST AND SUPPER

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ADVANTAGESADVANTAGES

• SIMPLE AND EASY TO USE ;draw A SINGLE DOSE OF A COMBINATION OF INSULIN IN ONE SYRINGE

• MINIMUM INSULIN DOSING THAT PROVIDES 24-HOUR INSULIN COVERAGE

• HUMALOG MIX 75/25 INSULIN OR NOVO MIX 70/30 INSULIN CAN BE TAKEN 5-15 MINUTES BEFORE A MEAL

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DISADVANTAGESDISADVANTAGES

• 70/30 INSULIN ;SHOULD WAIT 30 MINUTES AFTER INSULIN INJECTION BEFORE EATING THE MEAL

• FIXED RATIO OF INTERMEDIATE AND SHORT OR RAPID ACTING INSULIN MAY NOT CONTROL BLOOD GLUCOSE LEVELS

• CAN NOT ADJUST INTERMEDIATE-ACTING INSULIN COMPONENT WITHOUT ADJUSTING THE SHORT OR RAPID ACTING INSULIN COMPONENT

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DISADVANTAGESDISADVANTAGES

• CAN NOT ADJUST REGULAR INSULIN,INSULINASPART, OR INSULIN LISPRO FOR VARIATION IN FOOD INTAKE, BLOOD GLUCOSE LEVELS OR EXERCISE

• MUST TAKE INSULIN AND EAT MEALS ABOUT THE SAME TIME EVERY DAY MUST EAT ACONSISTANT AMOUNT OF CARBOHYDRATES AT EACH MEAL FROM DAY TO DAY

• LEAST FLEXABLE OF ALL REGIMENS

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INDICATIONSINDICATIONS

• PATIENTS WITH LIMITED CAPABILITIES

• PATIENTS WHO ARE UNWILLING TO INTENSIFY REGIMEN

• INITIAL REGIMEN AFTER DIAGNOSES TO LEARN AND ADAPT TO INJECTIONS

• TYPE 2 DIABETES04/11/2304/11/23 4848

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STARTING DOSESTARTING DOSE

• 2/3 TOTAL DAILY DOSE BEFORE BREAKFAST ,1/3 TOTAL DAILY DOSE BEFORE SUPPER

• 0.5—1.0 U/KG/DAY

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Pre-mix (Pre-mix (70/3070/30))• Gaps in insulin coverage

• Poor long-term control

• Failure to match endogenous secretion pattern

• Dawn phenomenon

• Increased glycaemia

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Can Oral hypoglycaemic agents

be continued at the same time with insulin?

• Metformin Best continued if renal function is normal. May

reduce insulin requirements by 15-30%.• Adjunctive weight reducing effect

• Thiazolidinediones • May be continued with insulin. • Can reduce insulin requirements from 15-60% • Major issue of weight gain, accentuated by

insulin: 7.5%. 15%>5kg.

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Can Oral hypoglycaemic agents

be continued at the same time with insulin?

• Sulphonylureas

• Glimeperide: doses of 2-4mg a day have a peripheral GLUT-4 activity reducing insulin requirement by 10-20%.

• Glipizide and Glibenclemide can reduce insulin requirements by 5-15%.

• Unpredictable- recommended previously in those with high C-peptide levels

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Insulin administration is suitably as premixed fashion for Insulin administration is suitably as premixed fashion for most type 2 diabetes. Split-mix may be required in a most type 2 diabetes. Split-mix may be required in a subset. subset.

The neccessity of self blood glucose monitoring as a The neccessity of self blood glucose monitoring as a accessory is emphasized. accessory is emphasized.

Summarizing……..Summarizing……..

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Aggressively Titrated Premix

70/30+Met+Pio Met+Pio

Baseline A1C 8.1±1.0 7.9±0.9

EOS A1C 6.5±1.0 7.8±1.2

Percentage of Patients With A1C (EOS)

<7.0% 76.3 24.1

≤6.5 59.1 11.5

≤6.0 33.3 2.3

≤5.5 14.0 0

FPG (mg/dl) 130±50 162±41

Raskin et al. Insulin 2007;2 (suppl A):S1104/11/23 55

Comparison of Common Insulin Regimens*

Variable Glargine* NPH1 Premix2,3 Detemir4

Efficacy Insulin Works

Hypoglycemia† 1.0 1.4X 2.5-5.0X 1.0

Insulin Dose 1.0 1.0 1.5-2.0X 1.6-2.1X

Weight Gain 1.0 1.0 1.5X 0.7-1.0X

*Normalized to glargine; sponsored comparator trials †Confirmed hypoglycemia1Riddle MC et al. Diabetes Care 2003;26:3080-3086 2Janka HU et al. Diabetes Care 2005;28:254-259 3Raskin P et al. Diabetes Care 2005;28:260-265 4Rosenstock J et al. ADA 2006; Abstract 555-P

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04/11/2304/11/23 DR MAXUD DIABETOLOGISTDR MAXUD DIABETOLOGIST 5959

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