2015 PDCI Core Kit 3b PERKENI Standards of Medical Care -

Standards of Medical Care

Learning Objectives

• Discuss the PERKENI Diabetes Mellitus National Practice Guidelines/Standards of Care

• Review a summary of the ADA Standards of Care for preventing, diagnosing and treating prediabetes and diabetes

Standards of Care: PERKENI and ADA

• PERKENI created “Diabetes Mellitus National Clinical Practice Guidelines” (2011-revises)

• ADA Standards of Medical Care in Diabetes composes all current and key clinical recommendations from the ADA

PERKENI: Standards of Care

• Diabetes care must be:– Continuous, not episodic

– Proactive, not reactive

– Planned, not sporadic

– Patient centered rather than provider centered

– Population based, as well as individual based

– Team care

PERKENI: Standards of Care

• Ideal core team members:

– A physician

– A nurse

– A dietician

– at least one of whom is certified diabetes educator

• Other team members will vary according to the patient

need, patient load, organization constraints, resources,

clinical setting and professional skills

– e.g.: podiatrist, pharmacist, psychological or social workers

Mensing C. Diabetes Care 2000:23:682-9.

PERKENI: Screening

• Screening is conducted on those who have diabetes risks, but do not show any symptoms of DM.

• Screening seeks to capture undiagnosed DM or prediabetes so it can be managed earlier and more appropriately.

• Mass screening is not recommended considering the costs, which are generally not followed by action plan for those who were found abnormal.

Prevention/ Delay of T2DM

PERKENI: Diabetes Prevention

High-risk population at >30-year old

• Family history of DM• Cardiovascular disorder• Overweight• Sedentary life style• Known IFG or IGT• Hypertension• Elevated triglyceride, low

HDL or both• History of Gestational DM• History of given birth

> 4000g• PCOS

• Medical Nutritional Therapy

• Physical activity

• Weight reduction

• If overweight, reduce body weight by 5-10%

• Physical exercise for 30 minutes,

5 times/week, or 150 minutes/week

• Not yet recommended

Early Detection Lifestyle ChangesPharmacology

Therapy

Periodic Blood Glucose & Risk

Factor Monitoring

• Hypertension

• Dyslipidemia

• Physical health

• Body weight control

• 2-hour OGTT is the most sensitive method for early detection and a recommended screening test procedure

Management

Diagnosis

Screening/Testing for Diabetes in

Asymptomatic Patients

PERKENI Guidelines 2011

Diabetes Symptoms

Diabetes Classic Symptoms (+) Diabetes Classic Symptoms (-)

FBG ≥126 <126

RBG >200 <200

FBG and PPG

FBG >126 <126

RBG ≥200 <200

Diabetes Mellitus

FBG ≥126 100-125

RBS >200 140-199

<100

<140

OGTT 2 hour BG

Evaluation of Nutritional StatusEvaluation Diabetic Complications

Evaluation Dietary Need and Dietary Planning

>200 140-199

IGT IFG Normal

<140

EducationDietary Planning

Physical ExerciseAchieving Ideal Body Weight

atau atau

atau

FBG = Fasting Blood GlucoseRBG = Random Blood GlucoseIGT = Impaired Glucose ToleranceIFG = Impaired Fasting Glucose

PERKENI: Diagnostic Criteria for Diabetes Mellitus

• Classic symptoms of diabetes + random glucose plasma level ≥ 200 mg/dL. Random glucose plasma level is a test which access glucose plasma level at a single time without concerning about last meal schedule.

or• Classical symptoms of diabetes + fasting plasma glucose

≥ 126 mg/dL. Fasting means patients not getting intake calories for minimum 8 hours.

or• 2-h plasma glucose at glucose tolerance test ≥ 200 mg/dL.

Glucose tolerance test done by the WHO standard using 75g anhydrous glucose which solvent in the 100 cc water

or• HbA1c ≥ 6.5%

PERKENI GUIDELINES 2011-revices

PERKENI: Standard Values of Random Blood Glucose and Fasting Blood Glucose for Screening and Diagnosis of DM (mg/dL)

Non DM Uncertain DM DM

Random blood glucose level(mg/dL)

Venous plasma

<100 100-199 ≥200

Capillary blood <90 90-199 ≥200

Fasting blood glucose level (mg/dL)

Venous plasma

<100 100-125 ≥126

Capillary blood <90 90-99 ≥100

Note: For high-risk groups which show no abnormal results, the test should be done every year. For those aged > 45 years without other risk factors, screening can be done every 3 years.

PERKENI GUIDELINES 2011-revices

HbA1c

• Check at first visit

– Used as tool for diagnosis (≥6.5%)

• Every 3 months later on (at least every 6 months)

– For blood control evaluation

PERKENI GUIDELINES 2011-revices

Diabetes Care

Target of Treatment

Risk CVD (-) Risk CVD (+)

BMI (kg/m2) 18.5 – <23 18.5 – <23

Blood Glucose

• FPG (mg/dL) <100 <100

• Post Prandial BG (mg/dL) <140 <140-180

A1C (%) <7.0 <7.0

Blood Pressure <130/80 <130/80

Lipid

Total Cholesterol (mg/dL) <200 <200

Triglyceride (mg/dL) <150 <150

HDL Cholesterol (mg/dL) >40 / >50 >40 / >50

LDL Cholesterol (mg/dL) <100 <70

PERKENI GUIDELINES 2011-revices

Strategies for Improving Diabetes Care

Diabetes Self-Management

Team Care:

Physician

Nurse

Dietitian

Educator

Role of Team Members

To prepare people with diabetes to make self-management

decisions on their own

People with diabetes are at the center of the health team and

can learn to self-manage their diabetes

Who’s teaching the diabetics? Etzwiler DD. Diabetes 1967:16:111-7.

PERKENI: Patient Education

• Daily activities– Be active most of the time

– Be productive

• Self-management skills– Preparing pills, insulin

– Follow drug schedule

– Side effect awareness

• Foot care– Daily foot care & appropriate shoes

• Medical checkup

PERKENI: Patient Education

• Healthy eating: – healthy food choices, food composition (carbs, protein,

fat, fiber)

• Body weight maintenance: – achieved target of BMI or reduced 5 – 10% of body

weight

• Exercise• Monitoring:

– self-monitoring of blood glucose, A1C

• Hypoglycemia: awareness & self-treatment

Self-Monitoring of Blood Glucose (SMBG)

SMBG: one tool to assess therapy in diabetic patients that is

recommended especially in:

• Patients that will undergo insulin therapy

• Patients receiving insulin therapy

• Patients with A1C level did not reach the target

• Women planned for pregnancy / pregnant women with

hyperglycemia

• Patients with recurrent hypoglycemia.

Diabetes Management – DiabCare Asia 2008 – Type of Management

Diabetes Management Variable n (%)*

Type of Management

• Diet only -

• OAD Insulin monotherapy 1133 (61.88)

• Insulin monotherapy 317 (17.31) 35

• Insulin and OAD combination 356 (19.44)

• Herbal 5 (0.27)

• None 20 (1.09)

*n = 1785

Soewondo P. Med J Indones 2010;19(4):235-244

Diabetes Management – DiabCare Asia 2008 – Type of OAD Therapy

Diabetes Management Variable n (%)*

Type of OAD Therapy

• Biguanides 1085 (59.26)

• Sulphonylureas 1036 (56.58)

• Meglinitides 8 (0.44)

• Alpha glucosidase inhibitors 461 (25.18)

• TZDs 51 (2.79)

• Other OADs 48 (2.62)

• Traditional herbal medicines 5 (0.27)

• Double drug fixed dose combination 88 (4.81)

Soewondo P. Med J Indones 2010;19(4):235-244

DM Phase - I Phase - II Phase - III

Lifestyle Modification

+

Intensive Insulin

Alternative:• Insulin not available• Patient preference• Glucose control not

optimal

Lifestyle Modification

OAD Monotherapy +

Lifestyle Modification

2 OADs Combination

+

Lifestyle Modification

2 OADs Combination

Basal Insulin

+

+

Lifestyle Modification

3 OADs Combination

Notes:Fail: not achieving A1c target < 7% after 2-3 months of treatment(A1c = average blood glucose conversion, ADA 2010)

PERKENI Guidelines 2011-revice

< 7% 7 – 8% 8 - 9% > 9% 9 - 10% > 10%

Lifestyle Modification

Lifestyle Modification

+

Monotherapy

Met, SU, AGI, Glinid, TZD,

DPP-IV

Lifestyle Modification

+

2 OADs Combination

Met, SU, AGI, Glinid, TZD,

DPP-IV

Lifestyle Modification

+

3 OADs Combination

Met, SU, AGI, Glinid, TZD,

DPP-IV

Lifestyle Modification

+

2 OADs Combination

Met, SU, AGI, Glinid, TZD,

DPP-IV

+

Basal Insulin

Lifestyle Modification

+

Intensive Insulin

Notes:Fail: not achieving A1c target < 7% after 2-3 months of treatment(A1c = average blood glucose conversion, ADA 2010)

PERKENI Guidelines 2011-revice

Study Microvasc CVD Mortality

UKPDS DCCT / EDIC*

ACCORD ADVANCE

VADT

Long Term Follow-up

Initial Trial

* in T1DM

Kendall DM, Bergenstal RM. © International Diabetes Center 2009

UK Prospective Diabetes Study (UKPDS) Group. Lancet 1998;352:854.

Holman RR et al. N Engl J Med. 2008;359:1577. DCCT Research Group. N Engl J Med 1993;329;977.

Nathan DM et al. N Engl J Med. 2005;353:2643. Gerstein HC et al. N Engl J Med. 2008;358:2545.

Patel A et al. N Engl J Med 2008;358:2560. Duckworth W et al. N Engl J Med 2009;360:129. (erratum:

Moritz T. N Engl J Med 2009;361:1024)

Impact of Intensive Therapy for Diabetes: Summary of Major Clinical Trials

Individualized target of therapy

Most Intensive Level Approximately 6.0%

Factors Least Intensive Level Approximately 8.0%

Highly motivated, adherent,

knowledgeable, strong self-care capability

Psychosocial considerations

Less motivated, non-adherent, less

knowledge, weak self-care capability

Adequate Resources or support systems

inadequate

Low Risk of hypoglycemia High

Short Duration of type-2 DM long

Long Life expectancy Short

None Microvascular disease Advances

None Cardiovascular disease Established

None Coexisting conditions Multiple, severe, or both

Ismail-Beigi. N Engl J Med 366:1319, 2012

Glycated Hemoglobin Range

Suggested goals for Glycemic Treatment in Patients with Type-2 Diabetes

METF DPP-4 I GLP1 RA TZD AGI COL SVL

BCR OR

SU/glinide

INSULIN SGLT2 PRAML

HYPOs

Neutral Neutral Neutral Neutral Neutral Neutral Neutral

Moderate to severe

Mild

Moderate to severe

Neutral Neutral

Weight Slight loss Neutral Loss Gain Neutral Neutral Neutral Gain Gain Loss Loss

Renal / GU Contra indicated grd 3B,4,5

Neutral ?Exenaitide

contra indicate in clr crt<30%

May worsen

fluid retention

Neutral Neutral Neutral More

hypoglycemia

More hypo risk & fluid retention

Infection Neutral

GI Sx Moderate Neutral Moderate Neutral Moderate Mild Moderate Neutral Neutral Neutral Moderate

CHF Neutral Neutral Neutral Moderate Neutral Neutral Neutral Neutral Neutral Neutral Neutral

CVD Benefit Neutral Neutral Neutral Neutral Neutral Benefit ? Neutral Neutral Neutral

BONE Neutral Neutral neutral Moderate bone loss

Neutral Neutral Neutral Neutral Neutral Bone loss?

Neutral

Few adverse events or possible benefits

Used with caution Likelihood of adverse events

Profiles of Antidiabetic Medications

Comorbid Drugs

Recurrent HYPOs Metformin / GLP-1RA / DPP4-inh / AGI / TZD

Overweight / Obese GLP-1RA / DPP4-I / Metformin / AGI

Cardiovascular Diseases Metformin / TZD / incretin Tx (?)

Congestive Heart Failure Insulin / Metformin (±) / Incretin Tx

Chronic Kidney Disease Insulin / DPP4-I or AGI (adjust dose)

Liver diseases Insulin, TZD (hepatosteatosis), DPP4-I (?)

Type-2 Diabetic Patients Lifestyle intervention + 1st initial drug

A1c not at target

Existing A1c and A1c Target of Tx

Stringent group A1c target <7%

Less Stringent group A1c target ±8%

Gap between existing A1c and target of Tx > 2% Gap between existing A1c

and target of Tx < 2%

insulin

Other drugs than metformin can be used as initial treatment in some cases

Treatment Approach

Detection and Diagnosis Gestational Diabetes

(GDM)

Gestational Diabetes Mellitus (GDM)

• Diagnosis of GDM based on OGTT (75 g glucose orally)• Diagnose:

– FBG ≥ 95 mg/dl; 1 hr PP ≥ 180 mg/dl; 2 hr PP ≥ 150 mg/dl

• Manage by team care– Objective: to reduce morbidity and mortality of the mother and

the baby

• Target of treatment– FBG : ≤95 mg/dl– 2hrPP : ≤120 mg/dl

Assessment of Common Comorbid Complications

Dyslipidemia

• Dyslipidemia increases cardiovascular risk• Check lipid profile in first visit newly diabetic

patient and repeat at least every 1 year• Target of treatment:

– LDL: • Without CVD < 100 mg/dl• With CVD < 70 mg/dl

– HDL:• Men > 40 mg/dl; women > 50 mg/dl

– TG: • <150 mg/dl

• Therapy:– Non pharmacology– Pharmacology: statin, fibrate, niacin

Hypertension

• Initiation therapy when BP: >130/80 mmHg• Target of treatment: 130/80 mmHg• Therapy:

– Non pharmacology• Reduce BW• Exercise• Stop smoking and alcohol• Reduce salt intake

– Pharmacology:• ACE-I• ARB• CCB• Low dose diuretic• Alpha-receptor blocker

Anti Platelet coagulation

• Low dose aspirin (75-160 mg/day), is used for:– Diabetic patients with cardiovascular risk– Patient > 40 years old

• Not recommended for patient < 21 years old• Combination with other anti-platelet use for

patient with high risk• Other anti-platelet is used for patient with

intolerance to aspirin

Nephropathy

• Assess urine albumin excretion annually– Persistence micro-albuminuria (30-299 mg/24 hrs)

indicated DN

• Measure albumin/creatinine ratio annually

• Control blood glucose

• Control blood pressure

Recommendations: Hypoglycemia

• Glucose (15 – 20g) preferred treatment for conscious individual with hypoglycemia

• Check blood glucose 15 minute after glucose therapy (oraly/iv)

• Glucagon should be prescribed for all individuals at significant risk of severe hypoglycemia and caregivers/family members instructed in administration

• Those with hypoglycemia unawareness or ≥ 1 episodes of severe hypoglycemia should raise glycemic targets to reduce risk of future episodes

ADA. V. Diabetes Care. Diabetes Care 2012;35(suppl 1):S27.

Summary

• According to the most recent PERKENI and ADA Standards of Care:– optimal diabetes care requires appropriate and

evidence-based prevention, screening, diagnosis, treatment and educational strategies.

40

Thank You

41

Oral Diabetes Drugs in Indonesia

Class Generic name

Trade name mg/tab Daily dose (mg) Duration of action (hrs)

Freq/day Taking time

Sulfonylurea

Glibenclamid Daonil 2.5 – 5 2.5 – 15 12 – 24 1 – 2

Before meal

GlipizidMinidiab 5 – 10 5 – 20 10 – 16 1 – 2

Glucotrol-XL 5 – 10 5 – 20 12 – 16** 1

GliklazidDiamicron 80 80 – 320 10 – 20 1 – 2

Diamicron-MR 30 – 60 30 – 120 24 1

Glikuidon Glurenorm 30 30 – 120 6 – 8 2 – 3

Glimepirid

Amaryl 1-2-3-4 0.5 – 6 24 1

Gluvas 1-2-3-4 1 – 6 24 1

Amadiab 1-2-3-4 1 – 6 24 1

Metrix 1-2-3-4 1 – 6 24 1

GlinideRepaglinid Dexanorm 1 1.5 – 6 3

Nateglinid Starlix 120 360 – 3

Thiazolidinedione Pioglitazone

Actos 15 – 30 15 – 45 24 1Not depend on meal

Deculin 15 – 30 15 – 45 24 1

Pionix 15 – 30 15 – 45 18 – 24 1

Gluckosidase alpha inhibitor

AcarboseGlucobay 50 – 100 100 – 300 3

First spoonEclid 50 – 100 100 – 300 3

Biguanide

MetforminGlucophage 500 – 850 250 – 3000 6 – 8 1 – 3

With/after meal

Glumin 500 500 – 3000 6 – 8 2 – 3

Metformin XRGlucophage XR 500 – 750 24 1

Glumin XR 500 500 – 2000 24 1

Oral Diabetes Drugs in Indonesia

Class Generic name

Trade name mg/tab Daily dose (mg) Duration of action (hrs)

Freq/day Taking time

DPP-IV inhibitors

Vildagliptin Galvus 50 50 – 100 12 – 24 1 – 2Not depend on meal

Sitagliptin Januvia 25, 50, 100 25 – 100 24 1

Saxagliptin Onglyza 5 5 24 1

Fixed combintaion

Metformin + Glibenclamid

Glucovance

250/1.25Max dose of

glibenclamid 20 mg/day12 – 24 1 – 2

With / after meal

500/2.5

500/5

Glimepirid + Metformin

Amaryl-Met FDC1/250 2/500 2

2/500 4/1000

Pioglitazone + Metformin

Pionix M15/500 Max dose of

pioglitazone 45 mg/day18 – 24 1

30/850

Sitagliptin + Metformin

Janumet50/500 Max dose of sitagliptin

100 mg/hari1

50/1000

Vildagliptin + Metformin

Galvusmet

50/500Max dose of

vildagliptin 100 mg/hari12 – 24 250/850

50/1000

Insulin in Indonesia

Insulin Onset of action Peak of action Duration of action

Insulin Prandial (Meal Related)

Insulin Short Acting

Reguler (Actrapid®, Humulin® R) 30-60 minute 30-90 minute 3-5 hrs Vial, pen/cartridge

Insulin Analog Rapid Acting

Insulin Lispro (Humalog®) 5-15 minute 30-90 minute 3-5 hrs Pen/cartridge

Insulin Glulisine (Apidra®) 5-15 minute 30-90 minute 3-5 hrs Pen

Insulin Aspart (Novorapid®) 5-15 minute 30-90 minute 3-5 hrs Pen, Vial

Insulin Intermediate Acting

NPH (Insulatard®, Humulin® N) 2-4 hrs 4-10 hrs 10-16 hrs Vial, Pen/cartridge

Insulin Long Acting

Insulin Glargine (Lantus®) 2-4 hrs No Peak 20-24 hrs Pen

Insulin Detemir (Levemir®) 2-4 hrs No Peak 16-24 hrs Pen

Insulin Campuran

70% NPH 30% Reguler(Mixtard®, Humulin® 30/70)

30-60 minute Dual 10-16 hrs Pen/cartridge

70% Insulin Aspart Protamin 30% Insulin Aspart (Novomix® 30)

10-20 minute Dual 15-18 hrs Pen

75% Insulin Lispro Protamin30% Insulin Lispro (HumalogMix® 25)

5-15 minute Dual 16-18 hrs Pen/cartridge

Class Mechanism Advantages Disadvantages CostBiguanides • Activates AMP-

kinase• Hepatic glucose production

• Extensive experience• No hypoglycemia• Weight neutral• ? CVD

• Gastrointestinal• Lactic acidosis• B-12 deficiency• CKD

Low

SUs / Meglitinides

• Closes K-ATP- channels• Insulin secretion

• Extensive experience• Microvasc. risk

• Hypoglycemia• Weight gain• Low durability• ? Ischemic preconditioning

Low

TZDs • PPAR-g activator• insulin sensitivity

• No hypoglycemia• Durability• TGs, HDL-C • ? CVD (pio)

• Weight gain• Edema / heart failure• Bone fractures• ? MI (rosi)• ? Bladder ca (pio)

High

Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of print]

DPP-4inhibitors

• Inhibits DPP-4• Increases GLP-1, GIP

• No hypoglycemia• Well tolerated

• Modest A1c • ? Pancreatitis• Urticaria

High

Properties of anti-hyperglycemic agents

Class Mechanism Advantages Disadvantages Costa-GIs • Inhibits -a

glucosidase• Slows carbohydrate absorption

• No hypoglycemia• Nonsystemic• Post-prandial glucose• ? CVD events

• Gastrointestinal• Dosing frequency• Modest A1c

Mod.

GLP-1 receptor agonists

• Activates GLP-1 R• Insulin, • glucagon• gastric emptying• satiety

• Weight loss• No hypoglycemia• ? Beta cell mass• ? CV protection

• GI• ? Pancreatitis• ? Medullary cancer • Injectable

High

Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of print]

Insulin • Activates insulin receptor• peripheral glucose uptake

• Universally effective• Unlimited efficacy• Microvascular risk

• Hypoglycemia• Weight gain• ? Mitogenicity• Injectable• Training requirements• “Stigma”

Variable

Properties of anti-hyperglycemic agents

First Line of Drugs

IDF 2012

AACE 2012

ADA – EASD 2014

NICE 2009

GSH

+

Intensive Insulin *

+

2 drugs combination

Met, SU,AGI, Glinid,

TZD

+

Basal Insulin

+

3 drugs combination

Met, SU,AGI, Glinide,TZD, DPP IV

+

2 drugs combination

Met, SU,AGI, Glinid,TZD, DPP IV

+

Monotherapy

Met, SU,AGI, Glinid,TZD, DPP IV

HLS

Healthy Lifestyle

• Reduced BW•Healthy Diet • Exercise

HbA1c

<7% <7-8% <8-9% 9-10% >10%

* Intensive insulin : basal bolus approach

HLS

HLS

HLS

HLS

HLS

Indonesian Society of Endocrinology , 2011

Type-2 DM Drug Treatment Guideline

DIABETES

TARGET of TREATMENT< 7%

(more stringent)± 8%

(less stringent)

CO-CONDITIONS DRUGS CHOICES

Recurrent HYPOs

Cardio Vascular Disease

Congestive Heart Failure

Chronic Kidney Disease

Liver disease

Overweight / obese

?

?

?

?

?

?

Gap of A1c to target ?

Treatment approach