Diabetes Diabetes MellitusMellitusin Clinical in Clinical PracticePractice

Dr. Muhieddin OmarDr. Muhieddin OmarDr. Raed Abu Sham’aDr. Raed Abu Sham’a

Definition of DiabetesDefinition of Diabetes It is a group of It is a group of metabolic diseasesmetabolic diseases

characterized by hyperglycemia characterized by hyperglycemia resulting from defects of resulting from defects of insulin insulin

secretion and/or increased cellular secretion and/or increased cellular resistance to insulinresistance to insulin. .

Chronic hyperglycemiaChronic hyperglycemia and other and other metabolic disturbances of DM lead to metabolic disturbances of DM lead to

long-term tissue and organ damage as long-term tissue and organ damage as well as dysfunction.well as dysfunction.

Type 2 diabetes is a major clinical and public Type 2 diabetes is a major clinical and public

health problem. health problem.

It is estimated that in the year 2000, 171 It is estimated that in the year 2000, 171 million people worldwide had type 2 diabetesmillion people worldwide had type 2 diabetes

In PalestineIn Palestine, the prevalence of diabetes , the prevalence of diabetes between 9 – 13% of the population.between 9 – 13% of the population.

Type 2 diabetesType 2 diabetesthe modern epidemicthe modern epidemic

Diabetes in the UK is Diabetes in the UK is increasingincreasing

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Adapted from: 1. Diabetes UK. Diabetes in the UK 2004. Diabetes UK, London, 2004.2. Diabetes UK. State of the Nation 2005. Diabetes UK, London, 2005.

How we How we

Diagnose Diabetes?Diagnose Diabetes?

Criteria for the diagnosis of Criteria for the diagnosis of DMDM

1.1. Symptoms of diabetes plus Symptoms of diabetes plus

random plasma glucoserandom plasma glucose

concentration >200 mg/dL.concentration >200 mg/dL.

2.2. Fasting plasma glucoseFasting plasma glucose >126 >126

mg/dL. (Fasting for at least 8 h.)mg/dL. (Fasting for at least 8 h.)

Criteria for the diagnosis of Criteria for the diagnosis of DMDM

3.3. Two-hour plasma glucoseTwo-hour plasma glucose >200 >200

mg/dL during an mg/dL during an OGTTOGTT (75 g). (75 g).

4.4. HbA1c > 6.5%HbA1c > 6.5% (ADA in 2010)(ADA in 2010)

Diagnosing Diabetes Using A1CDiagnosing Diabetes Using A1C

Diabetes diagnosed when A1C ≥6.5%Diabetes diagnosed when A1C ≥6.5%

Confirm with a repeat A1C test

Not necessary to confirm in symptomatic

persons with PG >200 mg/dL

If A1C testing not possible, use previous If A1C testing not possible, use previous

teststests

Can not be used during pregnancyCan not be used during pregnancy

because of changes in red cell turnoverbecause of changes in red cell turnover

July 2009, International Committee, American Diabetes Association & International Diabetes Federation

Diagnosing Diabetes Using A1CDiagnosing Diabetes Using A1C

A1C ≥6.0% should receive preventive A1C ≥6.0% should receive preventive

interventions (pre-diabetes)interventions (pre-diabetes)

A1C: reliable measure of chronic glucose A1C: reliable measure of chronic glucose

levels; values vary less than FPG and testing levels; values vary less than FPG and testing

more convenient for patients (can be done more convenient for patients (can be done

any time of day)any time of day)July 2009, International Committee, American Diabetes Association & International Diabetes Federation

Ease of testing- non fasting, one timeEase of testing- non fasting, one time

ReproducibilityReproducibility

ReliabilityReliability

Less variable than FBG that has Less variable than FBG that has 6-6-10% 10% intra-individual variability intra-individual variability

and the 2h PG that has variability and the 2h PG that has variability up to up to 15%15%

Diabetes CareDiabetes Care

Who should be screened for Who should be screened for diabetesdiabetes

All individuals >45 yearsAll individuals >45 years

If normal, repeat every 3 yearsIf normal, repeat every 3 years

Consider testing at a younger age Consider testing at a younger age or more frequently for high-risk or more frequently for high-risk individualsindividuals

HIGH-RISKHIGH-RISK Individuals Individuals

ObeseObese (BMI >27 kg/m²) (BMI >27 kg/m²)

Having a Having a first-degree relativefirst-degree relative with DMwith DM

High-risk High-risk ethnic populationethnic population

HIGH-RISKHIGH-RISK Individuals Individuals

Delivered a Delivered a baby weighing >4 kgbaby weighing >4 kg or or

gestational DMgestational DM

HypertensiveHypertensive (>140/90 mmHg) (>140/90 mmHg)

Having Having HDL-C <35HDL-C <35 mg/dL and/or a mg/dL and/or a

Triglyceride >250Triglyceride >250 mg/dL mg/dL

IGTIGT or or IFGIFG on previous testing on previous testing

In clinical settings . . .In clinical settings . . .

The The FPGFPG is preferred over the is preferred over the

OGTT due to: OGTT due to:

Ease of administration

Convenience, patient acceptability

Lower cost

Can we prevent or delay the Can we prevent or delay the

onset of Diabetes?onset of Diabetes?

Who should start the Who should start the preventionprevention

Strategies for prevention of Strategies for prevention of type 2 diabetestype 2 diabetes

1.1. Weight loss of 5 – 10%Weight loss of 5 – 10%

2.2. Physical activity ~ 30 min/dayPhysical activity ~ 30 min/day

3.3. Metformin [some patients]Metformin [some patients]

The Plate MethodThe Plate Method

Fruit Fruit Vegetables Vegetables

BreadsGrains StarchyVeggies

BreadsGrains StarchyVeggies

MeatsProteinsMeatsProteins

Dairy Dairy

Strategies for prevention of Strategies for prevention of type 2 diabetestype 2 diabetes (Con…) (Con…)

Monitoring for the development of diabetes Monitoring for the development of diabetes should be performed every should be performed every 1–2 years1–2 years..

Close attention and treatment for other Close attention and treatment for other CVD risk factors.CVD risk factors.

Drug therapy should not be routinely used Drug therapy should not be routinely used to prevent diabetes. to prevent diabetes.

However, metformin could be used However, metformin could be used cautiously in selected patients.cautiously in selected patients.

Management of

Diabetes

Type 2 Diabetes: Type 2 Diabetes: A Progressive DiseaseA Progressive Disease

LifestyleInterventions

Medical Nutrition Therapy

Alone

orwith Medications

Medical Nutrition Therapy

Medications

Insulin

Meds

Goals for Glycemic ControlGoals for Glycemic Control

Goals for Lipid ControlGoals for Lipid Control

Goals for BP ControlGoals for BP Control

< 130/80 mmHg< 130/80 mmHg

Stepwise Management Stepwise Management of Type 2 Diabetesof Type 2 Diabetes

Insulin ± oral agents

Oral combination

Oral monotherapy

Diet & exercise

How to follow up your How to follow up your

diabetic patient?diabetic patient?

Assessment guidelinesAssessment guidelines

EVERY VISITEVERY VISITBlood pressureBlood pressure

WeightWeight

Visual foot examinationVisual foot examination

QUARTERLYQUARTERLYHemoglobin A1CHemoglobin A1C

BIANNUALBIANNUALDental examinationDental examination

Assessment guidelinesAssessment guidelines

ANNUALLYANNUALLY

Albumin/creatinine ratioAlbumin/creatinine ratio (unless (unless

proteinuria is documented)proteinuria is documented)

Pedal Pedal pulsespulses and and neurologicneurologic examination examination

EyeEye examination (by ophthalmologist) examination (by ophthalmologist)

Blood Blood lipidslipids

Correlation of A1C with Average Correlation of A1C with Average GlucoseGlucose

Mean plasma glucoseMean plasma glucose

A1C (%)A1C (%)mg/dlmg/dl

66126126

77154154

88183183

99212212

1010240240

1111269269

1212298298

Diabetes Care 32(Suppl 1):S19, 2009

Glycemic ControlGlycemic Control

Each 1% reduction in mean HbA1c Each 1% reduction in mean HbA1c

was associated with:was associated with:

21% for deaths related to diabetes 21% for deaths related to diabetes

14% for myocardial infarction 14% for myocardial infarction

37% for microvascular complications 37% for microvascular complications

Stratton IM, Adler AI, Neil HA, et alStratton IM, Adler AI, Neil HA, et alBMJBMJ 2000 Aug 12;321(7258):405-12 2000 Aug 12;321(7258):405-12

Non-insulin agents in the Non-insulin agents in the management of type 2 management of type 2

diabetesdiabetes

InsulinInsulin in the Management of in the Management of

Type 2 DiabetesType 2 Diabetes

Combination between Combination between

InsulinInsulin and other and other

antihyperglycemicsantihyperglycemics

ConclusionsConclusionsMany, if not most, patients with Many, if not most, patients with

type 2 diabetes will eventually type 2 diabetes will eventually

require insulin to achieve their require insulin to achieve their

glycemic goals.glycemic goals.

Insulin should be offered to patients as Insulin should be offered to patients as

a safe and effective treatment option, a safe and effective treatment option,

not as a punishmentnot as a punishment

ConclusionsConclusions Insulin doses must be Insulin doses must be adjusted adjusted

frequentlyfrequently until the patient achieves until the patient achieves

the desired target.the desired target.

Treatment is initiated with a Treatment is initiated with a single single

bedtime injection of basal insulinbedtime injection of basal insulin

and the dose is titrated until the and the dose is titrated until the fasting fasting

glucose is normal.glucose is normal.

ConclusionsConclusions If the If the fasting glucose normalizesfasting glucose normalizes but the but the

A1C remains elevatedA1C remains elevated, additional , additional injections, typically given as injections, typically given as pre-meal pre-meal dosesdoses of rapid-acting insulin, may be of rapid-acting insulin, may be

required.required.

Patients with long-standing diabetes Patients with long-standing diabetes and non-obese, frequently may require and non-obese, frequently may require

multiple daily insulin injections.multiple daily insulin injections.

Take Home PointsTake Home Points When Oral Agents Fail, Add Basal Insulin When Oral Agents Fail, Add Basal Insulin

While Continuing OralsWhile Continuing Orals

Titrate Basal Insulin Titrate Basal Insulin RapidlyRapidly To Normalize To Normalize FBSFBS

When FBS Normal But A1C Elevated, Add When FBS Normal But A1C Elevated, Add Mealtime Bolus Insulin One Meal At A Mealtime Bolus Insulin One Meal At A

Time Time & Withdraw Sulfonylurea when & Withdraw Sulfonylurea when All Meals CoveredAll Meals Covered

Don’t Forget The ABC’s Don’t Forget The ABC’s

Complications of Complications of DiabetesDiabetes

Diabetic NephropathyDiabetic Nephropathy

Optimize glucose controlOptimize glucose control

Optimize blood pressure controlOptimize blood pressure control

Limit protein intake Limit protein intake

Test for microalbuminuria Test for microalbuminuria

Measure serum creatinine annually Measure serum creatinine annually

Treat with either ACE inhibitors or ARBsTreat with either ACE inhibitors or ARBs

Monitoring and Preventing Monitoring and Preventing HypertensionHypertension

BP should be measured at every routine BP should be measured at every routine

diabetes visit.diabetes visit.

Patients with diabetes should be treated Patients with diabetes should be treated

to a SBP <130/80 mmHg. to a SBP <130/80 mmHg.

Multiple drug therapy is generally Multiple drug therapy is generally

required to achieve targets.required to achieve targets.

Monitoring and Preventing Monitoring and Preventing HypertensionHypertension

Initial drug therapy for raised BP should Initial drug therapy for raised BP should

be with be with ACE inhibitors or ARBsACE inhibitors or ARBs

All patients with diabetes and All patients with diabetes and

hypertension should be treated with a hypertension should be treated with a

regimen that includes either an regimen that includes either an ACE ACE

inhibitor or an ARBinhibitor or an ARB..

Monitoring Lipid LevelsMonitoring Lipid Levels

In adults, test for lipid disorders at least In adults, test for lipid disorders at least annually and more often if needed to achieve annually and more often if needed to achieve

goals. goals.

Lifestyle modificationLifestyle modification including reduction including reduction of saturated fat and cholesterol intake, of saturated fat and cholesterol intake,

weight loss, and increased physical activity.weight loss, and increased physical activity.

In individuals without overt CVD, the primary In individuals without overt CVD, the primary goal is an LDL <100 mg/ dL. In those with goal is an LDL <100 mg/ dL. In those with

overt CVD, the goal is <70 mg/dL.overt CVD, the goal is <70 mg/dL.

Monitoring Lipid LevelsMonitoring Lipid Levels

For those over the age of 40 years, For those over the age of 40 years, statinstatin

therapy to achieve an therapy to achieve an LDL reduction of 30–LDL reduction of 30–

40% regardless of baseline LDL levels40% regardless of baseline LDL levels..

Lower Lower LDL cholesterolLDL cholesterol to <100 mg/dL to <100 mg/dL

Lower Lower triglyceridestriglycerides to <150 mg/dL to <150 mg/dL

Raise Raise HDL cholesterolHDL cholesterol to >40 mg/dL. to >40 mg/dL.

In women, an HDL goal should be >50 mg/dL.In women, an HDL goal should be >50 mg/dL.

The The AAction to ction to CControl ontrol

CCardiardiOOvascular vascular RRisk in isk in

DDiabetesiabetes

STUDY HYPOTHESIS:STUDY HYPOTHESIS:

A therapeutic strategy that targets HbA1c < 6.0%

reduces the rate of CVD events more than a

strategy that targets HbA1c 7.0% to 7.9%

ACCORDACCORD

257 Deaths257 Deaths In Intensive Arm In Intensive Arm

203 Deaths203 Deaths In Conventional Arm In Conventional Arm

Not Due To HypoglycemiaNot Due To Hypoglycemia

Not Due To MedicationNot Due To Medication

The ACCORD Study Group. N Engl J Med. 2008;358:2545-2559.The ACCORD Study Group. N Engl J Med. 2008;358:2545-2559.

ACCORD: Primary OutcomeACCORD: Primary Outcome

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YearsYears

PP=0.16=0.16

StandardStandard

IntensiveIntensive

ACCORD: All-Cause ACCORD: All-Cause MortalityMortality

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The ACCORD Study GroupThe ACCORD Study Group. N Engl J Med. N Engl J Med. 2008;358:2545-2559.. 2008;358:2545-2559.

PP=0.04=0.04

StandardStandard

IntensiveIntensive

ADVANCEADVANCEAction In Diabetes And Vascular Disease:Action In Diabetes And Vascular Disease:

Preterax And Diamicron MR Controlled Preterax And Diamicron MR Controlled EvaluationEvaluation

11,140 Patients, Age ~66, With Type 2 11,140 Patients, Age ~66, With Type 2 DM, And High CV RiskDM, And High CV Risk

Intensive (Intensive (A1c 6.4%A1c 6.4%) vs Conventional ) vs Conventional ((A1c 7%A1c 7%))

NoNo Excess Mortality In Intensive GroupExcess Mortality In Intensive Group

P=0.28

Advance Collaborative Group. New Engl. J. Med. 2008;358:2572.

ADVANCE: All-Cause MortalityADVANCE: All-Cause Mortality

P=0.32

Advance Collaborative Group. New Engl. J. Med. 2008;358:2572.Advance Collaborative Group. New Engl. J. Med. 2008;358:2572.

ADVANCE: Macrovascular EventsADVANCE: Macrovascular Events

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VADTVADTVeterans Affairs Diabetes TrialVeterans Affairs Diabetes Trial

Glycemic Control And CV EventsGlycemic Control And CV Events

Somewhat Less Intense Glycemic Somewhat Less Intense Glycemic Separation Separation ((6.9% vs 8.4%6.9% vs 8.4%))

Optimal CV Risk Factor ControlOptimal CV Risk Factor Control

Completed May And Presented At The Completed May And Presented At The ADA June, 2008ADA June, 2008

NoNo Excess Mortality In Intensive GroupExcess Mortality In Intensive Group

Hazard Ratio & CLHazard Ratio & CL

0.868 (0.728, 1.036) 0.868 (0.728, 1.036) PP=0.12=0.12

00 11 22 33 44 55 66 770.00.0

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0.80.8

1.01.0

Follow-Up (years)Follow-Up (years)

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Duckworth WC. ADA 68Duckworth WC. ADA 68thth Scientific Sessions; June 8, 2008; San Francisco, CA. Scientific Sessions; June 8, 2008; San Francisco, CA.

VADTVADT : Primary Outcome : Primary Outcome

StandardStandard

IntensiveIntensive

77Follow-Up (years)Follow-Up (years)

VADT: Total MortalityVADT: Total Mortality

Duckworth WC. ADA 68Duckworth WC. ADA 68thth Scientific Sessions; June 8, 2008; San Francisco, CA. Scientific Sessions; June 8, 2008; San Francisco, CA.

Hazard Ratio & CLHazard Ratio & CL

1.065 (0.801, 1.416) 1.065 (0.801, 1.416) PP=0.67=0.67

00 11 22 33 44 55 660.00.0

0.20.2

0.40.4

0.60.6

0.80.8

1.01.0

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StandardStandard

IntensiveIntensive

VA Diabetes TrialVA Diabetes TrialEnd of Trial Median End of Trial Median

ValuesValues BPBP LDLLDL

VADTVADT 127/69 127/69 72 72

ADVANCE 137/74ADVANCE 137/74 102 102

Abraira CA. ADA 68Abraira CA. ADA 68thth Scientific Sessions; June 8, 2008; San Francisco, CA. Scientific Sessions; June 8, 2008; San Francisco, CA.

ConclusionsConclusionsThe Overall Effect Of Glycemic Target The Overall Effect Of Glycemic Target

On On Macrovascular Events, If Any, Is Macrovascular Events, If Any, Is SmallSmall

Extremely Tight Glycemic Control In Extremely Tight Glycemic Control In Very Very High Risk Patients Is Not BenignHigh Risk Patients Is Not Benign

Lipid And BP Control, Smoking Cessation Lipid And BP Control, Smoking Cessation And Anti-platelet Therapy Remain And Anti-platelet Therapy Remain

Most Most Important For Reducing CVD Important For Reducing CVD Risk In Risk In Diabetes Diabetes

ADA Standards for Control

A1c

Normal < 6%

Goal <7%

Fasting: 90-130; HS 110-140

Goal <6.5%

Post-prandial < 140 mg

AACE Standards for Control

A1c As Close to Normal A1c As Close to Normal Without HypoglycemiaWithout HypoglycemiaAnd Goals Need to Be And Goals Need to Be

Individualized!Individualized!

Relative Risk of Progression of Relative Risk of Progression of Diabetic Complications Diabetic Complications

DCCT Research Group, N Engl J Med 1993, 329:977-986.

1

3

5

7

9

11

13

15

6 7 8 9 10 11 12

Retinop

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Mean A1C

UKPDS 35. BMJ 2000; 321: 405-12

Glycemic control and complicationsGlycemic control and complicationsUKPDS studyUKPDS study

0

20

40

60

80

0 5 6 7 8 9 10 11

Myocardialinfarction

Microvasculardisease

Updated mean HbA1c (%)

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The patients agenda may not be The patients agenda may not be yours ! ! ! !yours ! ! ! !

So remember…So remember…

Type 2 diabetes is largely Type 2 diabetes is largely asymptomatic and the treatments are asymptomatic and the treatments are inconvenient, impose on daily life and inconvenient, impose on daily life and

employmentemploymentThe patient’s agenda may be very The patient’s agenda may be very

different from yoursdifferent from yoursLifestyle change is the most important Lifestyle change is the most important

but the most difficult to achievebut the most difficult to achieveIn insulin-treated patients, In insulin-treated patients,

hypoglycaemia is a major risk, hypoglycaemia is a major risk, especially in the young and elderly.especially in the young and elderly.

SummarySummary

Most patients with type 2 diabetes still die of Most patients with type 2 diabetes still die of

cardiovascular disease regardless of their cardiovascular disease regardless of their

blood glucose control. blood glucose control.

Patients with highest HbA1c have most to Patients with highest HbA1c have most to

gain from any improvement in blood glucose gain from any improvement in blood glucose

controlcontrol