Updates in the Management of Diabetes Type 2

8/14/2019 Updates in the Management of Diabetes Type 2

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Updates in thepdates in theManagementanagementof Type 2 Diabetesf Type 2 Diabetes

Abdullah M. Kharbosh, B.Sc. Pharm


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Disorders of insulin action & secretion

It is characterized by symptomatic glucose intolerance as well asalterations in lipid & protein metabolism

Type 2 diabetes is the most common form of diabetes (90%)

What ?Typ

e 2 Introduction


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Type 2 diabetes is frequently undiagnosed for many yearsbecause hyperglycemia develops gradually & at earlier stages

It is often not severe enough for the patient to notice any of theclassic symptoms of diabetes

Nevertheless, such patients are at increased risk of developingMacro & Micro-vascular complications

What ?e 2

Introduction, contd


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What ?he

Red Zone

WHO report (2000)

More prevalenceLess population

Less prevalenceMore population

Genetic:Ethnicity Family history

Nutritional:Diet changeCalorie intake

Cultural:Physical activity

50% of the total Diabetic patients (~ 100 millions)50% of the total Diabetic patients (~ 100 millions)

0

5

10

15

20

25

W est co u n tries E ast co u n tries

Type 2 DM Prevalence


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Diseases Distribution in KSA - 2000

What ?e 2

High Prevalence in KSA

Diabetes is the leadingdisease that put a greatpressure on the health

system

0 5 10 15 20 25 30

Epilepsy

Tuberculosis

Hepatitis

Duodenal Ulcer

Asthma

Hypertension

Hyperlipidemia

Diabetes

%


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Obesity in KSA

What ?e 2

High Prevalence in KSA

44%32%

24%

NormalOver-weightObese


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Prevalence of Microvascular complications: Comparing dataComparing datafrom Arab countries with data of the highest & lowestfrom Arab countries with data of the highest & lowestprevalence world wide in the year 2000prevalence world wide in the year 2000

What ?e 2 High Prevalence in KSA

0

10

20

30

40

50

M w x i c

S a u d

i A r a U S A J a p a n S u d a n

S a u d

i A r a S p a i n T h a i l a n

S a u d

i A r a E g y p F r a n c

WHO report (2000)

Nephropathy

NeuropathyRetinopathy


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Homeostatic mechanisms maintain plasma glucoseconc. between 55 - 140 mg/dL (3.1 to 7.8 mmol/L)

A minimum concentration of 40 - 60 mg/dL(2.2 to 3.3 mmol/L) is required to provideadequate fuel for (CNS), which uses glucose as itsprimary energy source.

What ?boh ydrate Metabolism

CNS: Central Nervous System


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Blood glucose conc. exceed the re-absorptive capacityof the kidneys( 180 mg/dL ), glucose spills into theurine resulting in a loss of calories & water

Muscle & fat use glucose as major source of

energy, but these tissues require insulin for glucose uptake

If glucose is unavailable, these tissues are able to useamino acids & fatty acids for fuel



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Postprandial Glucose Metabolism in Nondiabetics


AA: Amino Acids; FFAs: Free Fatty Acids; TGs: Triglycerides

In muscle , insulin promotes the uptake of glucose& its storage as glycogen

It also stimulate the uptake of AA & their conversion toprotein

In adipose tissue , glucose is converted to FFAs &stored as TGs

Insulin prevents a breakdown of these TGs to FFAs

The liver doesn't require insulin for glucosetransport, but insulin facilitates the conversion of glucose to glycogen & FFAs


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Fasting Glucose Metabolism in Nondiabetics


Epi:Epinephrine; GH:Growth Hormone; GCs:Glucocorticoides

As blood glucose conc. drop toward normal during thefasting state, insulin release is inhibited

A number of counter regulatory hormones that promotean increase in blood sugar are released (e.g.,glucagon, Epi, GH, GCs )

Several processes maintain a minimum bloodglucose conc. for the CNS


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Fasting Glucose Metabolism in Nondiabetics Contd


AA: Amino Acids; FFAs: Free Fatty Acids; TGs: Triglycerides

Glycogen: in the liver glucose

AAs: transported from muscle liver glucose

Uptake of glucose by insulin dependent tissuesis diminished to conserve glucose for the brain

TGs are broken down into FFAs used as alternativefuel sources


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What ?yp e 2 Pathogenesis

(5) Excess glucose accumulationin the circulation

(2) Resistance to action of insulin

(6) HyperglycemiaStimulates thepancreasto produce more

insulin

(4) Glucoseoutput

(3) Glucoseutilization

(1) impaired Insulinsecretion

Hepatic Peripheral


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What ?Typ e 2 Risk Factors

Overweight/Obesity - Inactivity

HTN

A first degree relative with DM

Previous Gestational DM

Coronary Heart Disease

Dyslipidemia

Previously identified impaired fasting glucose (IFG) OR

Impaired glucose tolerance (IGT)


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What ?ype 2 Complications

Microvascular Microvascular Macrovascular Macrovascular Diabetic Retinopathy & CataractsLeading cause of 12.5% blindnesscases in working-age adults

Stroke2.5 fold increase in stroke

Diabetic NephropathyLeading cause of 42% of ESRD cases

Cardiovascular disease2 - 4 in HTN & CV Mortality25% of cardiac surgeries75% diabetics die from CV events

Erectile Dysfunction Peripheral Vascular Disease

Peripheral Neuropathy Diabetic FootLeading cause of 50% of all non-traumatic lower extremity amputations


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What ? Ty pe 2 Diagnosis

American Diabetes Association 2009

Diagnostic Criteria Of Type 2 DM

FPG 126 mg/dl (7 mmol/l). Fasting is defined as no caloric intakefor at least 8 h OR

A casual (random) plasma glucose 200 mg/dl (11.1 mmol/l) &symptoms of hyperglycemia OR

Results of a 2-hour 75- g OGTT > 200 mg/dl (11.1 mmol/l)


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What ? Ty pe 2 Screening

Screening of Asymptomatic Individuals

Screening of asymptomatic individuals at high risk for Type 2 DM should be carried out on an opportunistic basis

Screening should begin at age 40 years, & be considered at anearlier age (e.g. 30 years) if risk factors for DM are present

Screening should be carried out every 3 years for those withnormal glucose tolerance & annually for those with impairedfasting glucose (IFG) or impaired glucose tolerance (IGT)


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MANAGEMENT OF TYPE 2 DMCurrent Recommendations


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What ?Ma nagement Goals

Adapted from Applied Therapeutics, 2005

Biochemical IndexBiochemical Index GoalGoal

Pre-prandialPre-prandial GlucoseGlucose 9090 130130 mg/dlmg/dl

Blood Glucose EquivalentBlood Glucose Equivalent 8080 120120 mg/dlmg/dl

AverageAverage 22 -h-h PostprandialPostprandial PGPG


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What ?Ma nagement Goals

Adapted from Applied Therapeutics, 2005

Blood PressureBlood Pressure > 5050 >> 1.41.4LDL: Low Density LipoproteinHDL: High Density Lipoprotein

TG: Triglycerides


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What ?en t Old Stepped Care Approach

Lifestyle changes: Diet, Exercise, Smoking, LipidsLifestyle changes: Diet, Exercise, Smoking, Lipids

Single Oral AgentSingle Oral Agent

Combination Oral TherapyCombination Oral Therapy

Oral Therapy Plus InsulinOral Therapy Plus Insulin

InsulinInsulin

Insulin Plus Thiazolidinediones, Metformin, or SUInsulin Plus Thiazolidinediones, Metformin, or SU


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What ?ana gement Outcome

Diabetes is a reversiblepathological conditionthat can be done with:

ExerciseDietDrugs

Cumulative incidence of DM type 2 with:

placebo, metformin and lifestyle intervention

N Engl J Med 2002; 346: 393-403.


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What ?en t New Stepped Care Approach

Lifestyle Mod: Diet, Exercise, Smoking, LipidsLifestyle Mod: Diet, Exercise, Smoking, Lipids Single Oral AgentSingle Oral Agent

Combination Oral TherapyCombination Oral Therapy

Oral Therapy Plus InsulinOral Therapy Plus Insulin

InsulinInsulin

Insulin Plus Thiazolidinediones, Metformin, or SUInsulin Plus Thiazolidinediones, Metformin, or SU

PLUSPLUS


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What ?ent Medical Nutrition Therapy

Lifestyle ModificationLifestyle modification is a cornerstone of DM management &comprises the following: Medical Nutrition Therapy

Physical activity and exerciseAvoidance of smoking and alcoholic beverages

MNT & exercise prescription should be the initial therapy in:Obese (BMI > 30.0 ) &Overweight (BMI > 25.0 ) type 2 diabetic patients UNLESS they are:SYMPTOMATIC or SEVERELY HYPERGLYCEMIC


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What ?

MNT should be individualizedSaturated fat intake should not exceed 10%, with CHO 50-60% &Proteins 15-20% of total calorie intake

Diet should include foods from each of the basic food groups

An EXERCISE PROGRAM TAILORED to suit the individualsage, fitness, aptitude and interest should be prescribed

A PRE-EXERCISE EVALUATION to identify Macro-, Micro-

vascular & neurological complications is recommendedAn essential component of MNT is to avoid Smoking & Alcohol

What ?ent Medical Nutrition Therapy


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What ?em ent Antidiabetic Agents

- G l u c o s i d a s

e

I n h i b i t o r s

A c a r b o s e

M i g l i t o l

SulfonylureasGlibenclamideGliclazideGlipizide

Glimepiride

I n c r e t i n M i m

e t i c s

E x e n a t i d e

T h i a z o l i d i n e d i o n e s R o s i g l i t a z o n e P i o g l i t a z o n e

D P P - 4 I n h i b i t o r S i t a g l i p t i n

Am y l i n An a l o g P r a m l i n t i d e

G l i n i d e s

R e p a g l i n i d e

N a t e g l i n i d e

BiguanidesMetformin


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GLUCOSE ABSORPTION

GLUCOSE PRODUCTION

MUSCLE

PERIPHERAL GLUCOSE UPTAKE

PANCREAS

INSULIN SECRETION

ADIPOSE TISSUELIVER

Alpha-glucosidase inhibitors

INTESTINE

SU, Repaglinide, Nateglinide

Thiazolidinediones, MetforminThiazolidinediones, Metformin

iabetics Sites of Action

Sonnenberg, Kotchen Curr Opin Nephrol Hypertens 1998; 7:551-5.


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HypoglycemiaHypoglycemia WtWt EdemaEdema GIGI L. AcidosisL. Acidosis HepaticHepaticGlibenclamideGlibenclamide 4+ + 0 0

GliclazideGliclazide 2+ + 0 0

GlimepirideGlimepiride 2+ + 0 0

RepaglinideRepaglinide 1+ + 0 0 0 0NateglinideNateglinide 1+ ? 0 0 0 0

MetforminMetformin 0 0 0 2+ + 0

AcarboseAcarbose 0 0 0 3+ 0

RosiglitazoneRosiglitazone** 0 + + 0 0

PioglitazonePioglitazone** 0 + + 0 0 *

* Liver Enzyme Monitoring Recommended In Product Monographs

be tics Adverse Reactions

Adapted from Lebovitz H: Endocrinol & Metab Clinics of NA; 30 (4)909-933


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A1CA1C%% Wt (kgWt (kg)) DisadvantagesDisadvantages Other AdvantagesOther AdvantagesMetforminMetformin 1.5 Lactic acidosis TG 10-20% -

TC 5-10%Not Expensive

SUSU 1.5 2 Wt gain Not Expensive

RepaglinideRepaglinide 1.5 Wt gain Short Duration

AcarboseAcarbose 0.5-0.8 Expensive, TID dose Wt Neutral

TZDsTZDs 0.5-1.4 Expensive, Wt gain Improve lipid profile

ExenatideExenatide 0.5 1 2-3 Injections,Expensive,L

ittle experience

Weight loss

PramlintidePramlintide 0.5 0.7 1-1.5

idia betics Comparison


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Consider Consider AvoidAvoid

Renal FunctionRenal Function Glipizide, Glimepiride, Insulin, TZDs,Repaglinides

Acarbose, Metformin

Liver FunctionLiver Function Insulin, Repaglinide, Miglitol Acarbose, Metformin, TZDs

HyperlipidemiaHyperlipidemia Metformin, TZDs --------------------ObesityObesity Acarbose, Miglitol, Metformin Insulin, SU, Repaglanide

Hypoglycemia dueHypoglycemia dueto irregular eatingto irregular eatingpatternspatterns

Metformin, Acarbose, Repaglinide,TZDs

Insulin, Long acting SU

tics Use in Special Situations


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Step 1Step 1 Step 2Step 2 Step 3Step 3

1:Well-Validated

1:Well-Validated Lifestyle + Metformin

At diagnosis:Lifestyle

+Metformin

+Basal insulin

Lifestyle + Metformin+

Sulfonylurea


Intensive insulin


Pioglitazone


GLP-1 Agonist

No hypoglycemiaOedema/CHF/Bone loss

No hypoglycemiaWt loss/Nausea/Vomiting

Lifestyle + Metformin+ Pioglitazone

Sulfonylurea +

Lifestyle + Metformin+ Basal insulinGLP-1: Glucagon-like

peptide-1 (Exenatide)

Diabetes Care 2008 (Dec);31:1-11.

ment Stepwise Approach

2:Less Well-Validated

2:Less Well-Validated

In the last guideline try firstLSM if failed add meds.

Currently, Start LSM + medsat the diagnosis


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Diabetes Care 2008 (Dec);31:1-11.

ent Titration of Metformin

Begin with low dose (500 mg) OD or BID with meals or 850 mg OD

After 5-7 days, if no GI SEs, dose to 850 mg, or two 500 mg tablet, BID(before breakfast &/or dinner )

If GI SEs appear as doses advanced, to previous lower dose & try toadvance the dose at a later time

Max. effective dose can be up to 1 gm BID but is often 850 mg BIDModestly greater effectiveness has been observed with doses up toabout 2.5 gm/day. GI SEs may limit the dose that can be used

A longer acting formulations is available & can be given OD

1

2

3

4

5


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Start with HS intermediate acting or HS or AM LA insulin (can initiate with 10 U or 0.2 U/kg)

Check FG (usually daily) and dose, typically by 2 U Q3D until FG levels are consistently in target

range (3.9-7.2 mmol/l [70-130 mg/dl]). Can dose in larger increments, e.g., by 4 U Q3D, if FG is >10 mmol/l (180 mg/dl)

If hypoglycemia occurs, or FG level

Updates in the Management of Diabetes Type 2

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