diabetes mellitus cpg

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CLINICAL PRACTICE GUIDELINES FOR THE DIAGNOSIS AND MANAGEMENT OF DIABETES MELLITUS Ezekiel Arteta, M.D. Charlene Bularan, M.D. Department of Family and Community Medicine Ospital ng Maynila Medical Center

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Clinical Practice Guidelines for the Diagnosis and Management of Diabetes Mellitus in Pediatric, Adult and Pregnant age group

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Page 1: Diabetes Mellitus CPG

CLINICAL PRACTICE GUIDELINES FOR THE DIAGNOSIS AND MANAGEMENT OF DIABETES MELLITUS

Ezekiel Arteta, M.D.

Charlene Bularan, M.D.

Department of Family and Community Medicine

Ospital ng Maynila Medical Center

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OUTLINE

• Definition of Diabetes Mellitus• Classification• Spectrum• Summary of the Clinical Practice

Guidelines for each Specialty:• Pediatrics (AAP)• Medicine (ADA and PSEM)• Obstetrics (POGS)

• Pharmacology of Anti-Diabetic Drugs

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DIABETES MELLITUS

• Complex metabolic disorder characterized by persistent hyperglycemia resulting from:o Reduced insulin secretiono Decreased glucose utilizationo Increased glucose production

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CLASSIFICATION OF DIABETES MELLITUS

• Type 1 Diabetes (insulin-dependent/ Juvenile DM)o Complete or near-total insulin deficiencyo Caused by the autoimmune destruction of β-

cells of the pancreatic isletso May be idiopathic

• Type 2 Diabetes (non–insulin-dependent DM)o Variable degrees of insulin resistance, impaired

insulin secretion, and increased glucose production

• Gestational Diabetes Mellitus (Type 4)o DM that is diagnosed for the first time in

pregnancy

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DIFFERENTIATION BETWEEN TYPE 1 AND TYPE 2 DM

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DEFINITION OF DIABETES MELLITUS

TEST WHO ADA Philippine CPG

AACE IDF

Fasting Plasma Glucose

≥126 mg/dL (7.0 mmol/L)

2-h Plasma Glucose after 75-g OGTT

≥200 mg/dL (11.1 mmol/L)

HbA1c ≥6.5%

Random Plasma Glucose

≥200 mg/dL (11.1 mmol/L) + symptoms

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PRE-DIABETES

• Impaired Fasting Glucoseo FPG of 100–125 mg/dL (5.6–6.9

mmol/L) ADA, AACE, Phil. CPG

o FPG of 110–125 mg/dL (6.1–6.9 mmol/L) WHO:

• Impaired Glucose Toleranceo 2h 75-g OGTT of 140–199 mg/dL (7.8–

11.0 mmol/L) ADA, WHO, AACE, Phil. CPG

• Increased HbA1c (ADA)o HbA1c level of 5.7 – 6.4% ADA, WHO, Phil. CPG

o HbA1c level of 5.5 – 6.4% AACE

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DIABETES MELLITUS IN THE PEDIATRIC AGE GROUP

Sources:

American Academy of Pediatrics CPG on DMT2

American Diabetes Association CPG on DM

UNITE Philippines CPG on DM

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SCREENING FOR DIABETES MELLITUS

• Screening for Type 1 diabetes among children is NOT recommended because the disease appears to be of low prevalence; screening tests using serologic markers are not readily available and do not appear to be cost-effective; and there are as yet no clearly effective preventive approaches.

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SCREENING FOR DIABETES MELLITUS

• Screening for pre-diabetes and Type 2 DM is recommended among asymptomatic children commencing at age10 years or at onset of puberty , if puberty occurs at a younger age (ADA) with the following risk factors: (Grade C, Level 4):o Overweight (BMI > 85th percentile for age and

sex, weight-for-height > 85th percentile, or weight > 120% of ideal for height) OR

o Obese: BMI >95th centile or > +2SD

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SCREENING FOR DIABETES MELLITUS

• Screening for pre-diabetes and Type 2 DM is recommended among asymptomatic children commencing at age10 years or at onset of puberty , if puberty occurs at a younger age (ADA) with the following risk factors: (Grade C, Level 4):o Plus any 2 of the following risk factors

Family history (especially parents and grandparents) of Type 2 DM

Signs of insulin resistance (Acanthosis nigricans, hypertension, dyslipidemia, PCOS, or small for gestational age birth weight)

Maternal history of diabetes or GDM during the child’s gestation

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SCREENING FOR DIABETES MELLITUS

• Should screening for Type 2 DM be done in children?o Screening for pre-diabetes and Type 2 DM is

recommended among asymptomatic children commencing at age10 years or at onset of puberty, if puberty occurs at a younger age (ADA) with the following risk factors: (Grade C, Level 4):

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SCREENING FOR DIABETES MELLITUS

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DIABETES MELLITUS IN THE ADULT AND THE ELDERLY

Sources:

American Diabetes Association CPG on DM, 2013

UNITE Philippines CPG on DM

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SCREENING

• All individuals being seen at any physician’s clinic or by any healthcare provider should be evaluated annually for risk factors for type 2 diabetes and pre-diabetes. (Table 2) (Grade D, Level 5)

• Obesity, pre-diabetes, components of the metabolic syndrome, PCOS, previous GDM, family history and schizophrenia are some of the risk factors for DM.

• Universal screening using laboratory tests is not recommended as it would identify very few individuals who are at risk. (Grade D, Consensus)

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SCREENING

• Laboratory testing for diabetes and prediabetes is recommended for individuals with any of the risk factors for Type 2 diabetes mellitus. (Table 2) (Level 3-4, Grade B)

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SCREENING

• Testing should ideally be carried out within the health \care setting (clinics, hospitals, local health centers) because of the need for follow-up and discussion of abnormal results by qualified health care professionals (nurse, diabetes educator, physician). (Grade B, Level 3)

• Testing at any setting should be supervised by a qualified health care professional. (Grade D, Level 5)

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SCREENING

• If initial test/s are negative for diabetes, repeat testing should ideally be done annually. (Grade D, Level 5)

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DIAGNOSIS

• The diagnosis of Diabetes Mellitus can be made based on the following criteria*: (Grade B, Level 2) o Plasma glucose > 126 mg/dL (7.0 mmol/L) after

an overnight fasto Two-hour plasma glucose > 200 mg/dl (11.1

mmol/l) during an Oral Glucose Tolerance Testo A random plasma glucose > 200 mg/dl (11.1

mmol/l) in a patient with classic symptoms of hyperglycemia (weight loss, polyuria, polyphagia, polydipsia) or with signs and symptoms of hyperglycaemic crisis.

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DIAGNOSIS

• *Among ASYMPTOMATIC individuals with positive results, any of the three tests should be REPEATED within two weeks for confirmation. (Grade C, Level 4)

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DIAGNOSIS

• A 75-gram OGTT is preferred as the first test in the following individuals who have: (Grade B, Level 3) • A previous FBS showing Impaired Fasting

Glucose (100 to 125 mg/dL or 5.6 to 6.9 mmol/L)

• Previous diagnosis of Cardiovascular Disease (Coronary Artery Disease, Stroke, Peripheral Arteriovascular Disease) or who are at high risk for cardiovascular disease.

• A diagnosis of Metabolic Syndrome

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DIAGNOSIS

• At the present time, we cannot recommend the routine use of the following tests for the diagnosis of diabetes: (Grade C, Level 3)o HBA1c (because of poor access and lack of

standardiazation) o Capillary Blood Glucose o Fructosamine

However, if a result is available upon consultation due to prior testing, it should be interpreted with caution and should be confirmed by any of the 3 tests that are considered standard: fasting plasma glucose, oral glucose tolerance test or random plasma glucose. (Grade B, Level 2)

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DIAGNOSIS

• We do not recommend the following tests for the diagnosis of diabetes (Grade B, Level 3): o Urine glucoseo Plasma Insulin

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MANAGEMENT AND MONITORING

• Initial evaluation - comprehensive medical history and PEo Coronary heart disease risk assessmento Foot evaluation: assess risk for foot ulcer

(identify high-risk feet)o Eye exam: fundoscopy on diagnosiso Dental history or oral health history

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MANAGEMENT AND MONITORING

• Minimal initial tests to be requested• Fasting blood glucose, complete lipid profile• HbA1c• Liver function tests• Urinalysis; spot urine albumin-to-creatinine ratio• Serum creatinine and calculated GFR

• Optional tests• ECG and TET• TSH in type 1 diabetes, dyslipidemia or women

over age 50 y

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GLUCOSE CONTROL

  IDF AACE ADAHBA1c ≤6.5% ≤6.5% < 7%Preprandial plasma glucose

< 110 mg/dL

< 110 mg/dL

70-130 mg/dL

Peak postprandial glucose

NA < 140 mg/dL

< 180 mg/dL

Bedtime plasma glucose

NA NA 110-150 mg/dL

*Goals should be individualized*Certain populations require special considerations*Less intensive glycemic goals may be individualized in patients with frequent or severe hypoglycemia

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MANAGEMENT AND MONITORING

Glycemic targets should be achieved

within 6 months of diagnosis or first

prescription.

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MANAGEMENT

• The major components of the treatment of diabetes are:

• Diet and ExerciseA

• Oral hypoglycaemic therapyB

• Insulin TherapyC

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MANAGEMENT

• Diet is a basic part of management in every case. Treatment cannot be effective unless adequate attention is given to ensuring appropriate nutrition.

• Dietary treatment should aim at:• Ensuring weight control• Providing nutritional requirements• Allowing good glycaemic control with blood

glucose levels as close to normal as possible• Correcting any associated blood lipid

abnormalities• Controlling of blood pressure

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MANAGEMENT

• Protein:o Intake can range between 10-15% total energy

(0.8-1 g/kg of desirable body weight)o Should be derived from both animal and

vegetable sources. Recommended: One serving of protein from

animal sources every other day

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MANAGEMENT

• Carbohydrates:• Should be 50-60% of total caloric content of the

diet• Has the greatest effect on blood glucose• Enough Glucose available throughout the day

(not so much not little)• Consistent timing and composition of meals and

snacks from day to day• Evening snack helps prevent nocturnal

hypoglycemia

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Whole grain bread Cereals

LegumesFruits and Vegetables

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• ↑ GI can raise Blood glucose faster

• ↓ GI can raise Blood glucose slower

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MANAGEMENT

• Fats:o Should provide 25-35% of total intake of

calories o Saturated fat intake should not exceed 10% of

total energy. o Cholesterol consumption should be restricted

and limited to 300 mg or less dailyo With elevated LDL and overweight

Saturated fat: limit to 7% Cholesterol: limit to less than 200 mg daily

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MANAGEMENT

• Fats:o Low intake of unsaturated fat + high

carbohydrate + low total fat + energy intake = help lower LDL and cholesterol

o High monounsaturated fat diet Lower postprandial rise in blood glucose, insulin,

and triglycerides Does not improve fasting blood glucose

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MANAGEMENT

• Salto Excessive salt intake is to be avoided,

particularly in people with hypertension and those with nephropathy.

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MANAGEMENT AND MONITORING

• Initiate treatment with metformin for monotherapy unless with contraindications or intolerance of its ADE’so Diarrheao Severe nauseao Abdominal pain

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MANAGEMENT AND MONITORING

• When optimization of therapy is needed, choose the second drug according to the following -o Degree of HbA1c loweringo Hypoglycemia risko Weight gain/losso Patient profile (dosing complexity,

renal/hepatic problems, other contraindications and age)

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Sequence of Antihyperglycemic Therapy (ADA, 2012)

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MANAGEMENT AND MONITORING

• Since HbA1c reduction is the overriding goal, the precise combination used may not be as important as the glucose level achieved.

• There is no evidence that a specific combination is any more effective in lowering glucose levels or preventing complications than another.o SU + Pio = SU + Metformin (Hanefield et al, 2004 & Nagasaka et al, 2004)

o SU + Met = SU + DPP-IV inhibitors (?)

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MANAGEMENT AND MONITORING

• The goal BP for most persons with diabetes is <140/90 mm Hg.o Lifestyle therapy alone for 3 months if pre-

hypertensive (SBP 130-139 mm Hg or DBP 80-89 mm Hg)

o Pharmacologic + lifestyle therapy if SBP>140 mm Hg or DBP >90 mm Hg, or pre-hypertensive uncontrolled with lifestyle therapy alone

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MANAGEMENT AND MONITORING

• ACE inhibitors & ARBs are generally recommended as initial therapy. If one class is not tolerated, the other should be substituted.

• Multiple drug therapy (>2 agents at maximal doses) is generally required to achieve BP targets. Thiazide-type diuretics, calcium channel blockers and B-blockers may be given as additional agents.

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MANAGEMENT AND MONITORING

Recommendations are consistent with Philippine Practice Guidelines for the

Treatment of Dyslipidemia.

• LDL is the primary target for dyslipidemia management in persons with diabetes

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MANAGEMENT AND MONITORING

• Statin therapy should be added to lifestyle therapy, regardless of baseline levels for diabeticso With overt CVD (A)o Without CVD who are >40 y and have ≥1 more

other CVD risk factors (A)

• For patients at lower risk (e.g. without overt CVD and <40 y), statin therapy should be considered in addition to lifestyle therapy if• LDL-C remains >100 mg/dL• Those with multiple risk factors (hypertension,

familial hypercholesterolemia, LVH, smoking, family history of premature CAD, male sex, age >55 y, proteinuria, albuminuria, BMI>25)

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MANAGEMENT AND MONITORING

The 100-70 rule• Without overt CVD, goal is LDL-C <100

mg/dL (2.6 mmol/L) [A]• With overt CVD, goal is LDL-C <70 mg/dl

(1.8 mmol/L). Use of high dose statin is an option. [B]

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MANAGEMENT AND MONITORING

• Insufficient evidence to recommend aspirin for primary prevention in lower risk individualso Men < 50 yo Women <60 y

Clinical judgment if with multiple risk factors

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MANAGEMENT AND MONITORING

• Use aspirin therapy for secondary prevention strategy in those with DM and a history of CVD [A].

• For patients with CVD and documented aspirin allergy, clopidogrel (75 mg/day) should be used.

• Combination therapy of ASA (75-162 mg/day) and clopidogrel (75 mg/day) is reasonable up to a year after an acute coronary syndrome [B].

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LIPID PROFILE, BLOOD PRESSURE AND BMI TARGET

Parameter Ideal Acceptable Bad

TG <1.5 mmol/L(150 mg/dl)

<2.2mmol/L > 2.2 mmol/L

TC < 4.5mmol/L (200 mg/dl)

>4.5 mmol/L > 6.0 mmol/L

LDL < 2.5 mmol/L (100 mg/dl) < 4.4mmol/L > 4.4 mmol/L

HDL > 1.1 mmol/L(40 mg/dl in men; 50 mg/dl in women)

0.9-1.1mmol/L < 0.9 mmol/L

BP < 130/80mmHg >130/80-<140/90

> 140/90

BMI (Males) < 25 <27 ≥ 27

BMI (Females) < 24 <26 ≥26

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MANAGEMENT AND MONITORING

• The following patients must be referred to internists or diabetes specialists (endocrinologists or diabetologists) -o Type 1 diabeteso Moderate to severe hyperglycemiao Co-morbid conditions (infections, acute

CV events i.e. CHF or acute MI)o Significant hepatic and renal

impairmento Women with diabetes who are pregnant

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CLINICAL PRACTICE GUIDELINES FOR THE DIAGNOSIS AND MANAGEMENT OF DIABETES MELLITUS

Ezekiel Arteta, M.D.

Charlene Bularan, M.D.

Department of Family and Community Medicine

Ospital ng Maynila Medical Center

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CASE 3

A 29 y/o G1P0 26 weeks AOG by LMP, NIL came in for pre-natal check-up.

VS: 140/90 (done twice) – 89 – 20 – 37.0C

Patient’s FBS = 91 mg/dl at 26 weeks AOG. Test was repeated at 32 weeks AOG which revealed 114 mg/dl. UA revealed +1 albumin, +1 sugar.

Diagnosis?

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DIABETES MELLITUS IN PREGNANCY

Source:

Philippine Obstetrics and Gynecology Society CPG on DM

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EPIDEMIOLOGY

• 7% of all pregnancies are complicated with GDM worldwide

• In PH, 1.9% of pregnant women admitted have GDM

• 5.1% of Filipinas had DMT2 or GDM according to POGS, Inc.

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RISK FACTORS

• Increase overall and abdominal obesity• Sedentary lifestyle and change in diet

(caloric diet)• Cigarette smoking• Inadequate β cell response as seen

among Japanese population• LBW and undernutrition in utero• Genes (SEA descent)• Chronic infections (HBV and PTB)• Exposure to environmental irritants• Moderate Fe++ overload i.e.,

hemoglobinopathies

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ASSOCIATED DISEASES

• Childhood autism• Fetal overnutrition (macrosomia) and

insulin resistance

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COMPLICATIONS

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COMPLICATIONS

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SCREENING AND DETECTION

Recommendations for Filipino Pregnant Women• DM recognized during pregnancy may be classified

as either GDM or overt DM based on plasma glucose levels (Level III, Grade C)

• Universal screening for GDM is recommended among Filipino Gravidas (Level III, Grade B)

• At 1st PNCU determine if gravida is high risk accdg to history and risk factors (Level III, Grade B)

• If low risk, with normal intial test (FBS, HBA1c or RBS), screening should be done at 24-28 weeks AOG using 2 hr 75g OGTT

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SCREENING AND DETECTION

Recommendations for Filipino Pregnant Women• If OGTT is normal at 24-28 weeks AOG, re-test at

32 wks AOG or earlier if there are sx of hyperglycemia (3 P’s, plus polyhydramnios, accelerated fetal growth)

• OGTT should be performed in the morning after an overnight fasting of 8-14 hours.o Have an unrestricted diet 3 days or more prior

to testing, i.e., >/ 150 g of CHO per dayo Do not smoke and remain seated during the

test

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GDM WHO ADA POGS

FBS >125 mg/dL (6.9 mmol/L)

>92 mg/dL (5.1

mmol/dL)

>92 mg/dL (5.1

mmol/dL)

Overt: >/126 mg/dl (7 mmol/L)

1 hr >180 mg/dL (10 mmol/dL)

2 hr >140 mg/dL (7.8 mmol/dL)

>153 mg/dL (8.5

mmol/dL)

>140 mg/dL (7.8

mmol/dL)

Overt: >/ 200mg/dL

(11.1 mmol/L)

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TREATMENT

• DIET! – Medical Nutrition therapyo For normal-weight women (BMI: 20-25

kg/m2) 30 kcal/kg should be prescribed; o For overweight and obese women (BMI

> 24-34 kg/m2) calories should be restricted to 25 kcal/kg,

o For morbidly obese women (BMI > 34 kg/m2) calories should be restricted to 20 kcal/kg or less

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TREATMENT

• Weight Management – weight gain recommendations for women with GDM who had normal weight or were underweight prepregnancy is the same as for those without GDM

• Energy intake for overweight or obese women with GDM may be modestly restricted as long as weight gain is appropriate while minimizing risk of ketosis.

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TREATMENT

• Lifestyle changes – cessation of smoking and counseling about alcohol consumption.

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The most important thing in the reduction

of complications among women with GDM is glycemic

control…

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GOALS OF MANAGEMENT

OUTPATIENT GLUCOSE TRAGETS FOR PREGNANT WOMEN

For GDM treatment goals are: - Pre-prandial glucose concentration of

≤95mg/dL (5.3 mmol/L)- 1-hour postmeal glucose value of

≤140mg/dL (7.8 mmol/L)- 2-hour post meal glucose value of

≤120mg/dL (6.7 mmol/L)

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GOALS OF MANAGEMENT

For women with pre-existing DM type I or II who become pregnant, goals are:- Premeal, bedtime, and overnight glucose

values of 60-99mg/dL (3.3-5.4 mmol/L)- Peak post prandial glucose value of 100-

129mg/dL (5.4- 7.1 mmol/L)- HbA1c of ≤ 6%

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TREATMENT

The optimal treatment for women with GDM or type 2

DM who are not able to maintain normoglycemia with

CHO restricted diet INSULIN

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TREATMENT

Dosages:- 0.7-0.8 U/kg BW on 1st trimester- 1.0 U/kg BW on 2nd trimester- 1.2 U/kg BW on 3rd trimester

- 2/3 given before breakfast, 1/3 given before dinner (NPH insulin)

- Regular insulin and rapid acting insulin are best dosed with each meal

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TREATMENT

• Oral Hypoglycemic Agents use?o ACOG and the ADA do not currently

recommend oral hypoglycemic agents. 

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PHARMACOLOGY OF ANTI-DIABETIC DRUGS

Source:

Pharmacotherapy 101 by Dr. Agnes Cruz

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Sequence of Antihyperglycemic Therapy (ADA, 2012)

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ORAL HYPOGLYCEMIC AGENTS

Source: Pharmacotherapy 101 by Dr. Agnes Cruz

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• There are currently six classes of oral anti-diabetic agents: Biguanides Insulin Secretagogues – Sulphonylureas Insulin Secretagogues – Non-sulphonylureas α-glucosidase inhibitors Thiazolidinediones (TZDs) DPP-IV Inhibitors

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Drug Class Agents Mechanism of ActionAlpha-glucosidase

inhibitorsAcarboseVoglibose

Delay intestinal carbohydrate absorption

Biguanides Metformin

↓ Hepatic glucose production

↑ Liver and muscle insulin sensitivity

Insulin secretagogues—sulfonylureas

GlimepirideGlipizideGlyclazideGlibenclamide (glyburide)

↑ insulin secretion

Insulin secretagogues—Meglitinides

Nateglinide, Repaglinide ↑ insulin secretion

DPP-IV InhibitorsSitagliptinVildagliptinSaxagliptin

↑ Postrandial insulin secretion,

↓ glucagon secretion, Delay gastric emptying

ThiazolidinedionesPioglitazoneRosiglitazone

↑ Adipose and muscle insulin sensitivity

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Biguanide: METFORMIN

• Primary effects are to decrease hepatic glucose production and increase insulin-mediated peripheral glucose uptake

• Efficacy:

HbA1c• 1-2%• 11-22 mmol/mol

FPG• 40-70 mg/dl• 2.2-3.9 mmol/mol

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METFORMINSIDE EFFECTS CONTRAINDICATIONS DRUG

INTERACTIONPreparation

Lactic acidosis (rare; in patients with CHF)Diarrhea and abdominal discomfortWeight loss

Kidney failureLiver diseaseLactic acidosis

CimetidineFurosemideNifedipine

Tablets: 500, 850, and 1000 mg. Tablets (extended release): 500, 750, and 1000 mg. Solution: 500 mg/5 ml

• Usual dose:o 500 mg BID to TID

• Max dose:o 850 mg TID to 3g/day

• Max effective dose:o 1000 mg BID

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METFORMIN

BRAND NAME

STOCK DOSE

PRICE

RiteMed 500 3.09

Gludin 500 3.20

Neoform 500 3.35

Diamet 500 500 3.50

Pharex 500 3.75

Nidcor 500 4.32

Winthrop 500 4.50

Diafat 500 5.19

Glucoform 500 5.60

I-Max 500 5.60

BRAND NAME

STOCK DOSE

PRICE

Melta-SE 500 6.00

Neomet 500 6.00

Panfor SR 500 6.50

Ansures MR

500 7.00

Glumet 500 7.22

Fornidd 500 7.40

Euform Retard

850 8.90

Humamet 500 9.40

Glucophage 500, 750, 850

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Secretagogues

These medications try to replace the natural stimulus for beta cells to secrete insulin.

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SULFONYLUREAS• Efficacy:

HbA1c• 1-2%• 11-22 mmol/mol

FPG• 40-70 mg/dl• 2.2-3.9 mmol/mol

• Short-acting:o Tolbutamide

• Intermediate-acting:o Tolazamideo Glipizideo Glyburide/ Glibenclamide

• Long-acting:o Chloropropamideo Glimepiride

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SULFONYLUREASSIDE EFFECTS CONTRAINDICATIONS DRUG INTERACTION

HypoglycemiaWeight gain

IDDMDKADiabetic ComaPregnancy, Lactation

(next slide)

• Short-acting:o Tolbutamide: not available

• Intermediate-acting:o Tolazamide: not availableo Glipizide: Minidiab 5,10mg OD max: 40mg/do Glyburide/ Glibenclamide: Daonil 5mg Maintenance: 5-10 mg/day

• Long-acting:o Chloropropamide: not availableo Glimepiride: Aforglim 2, 3 mg ODo Glicazide: Diamicron 30, 80mg OD

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SULFONYLUREASBRAND NAME

GENERIC NAME

STOCK DOSE

PRICE

Benmide Glibenclamide 5 0.75

Azukon MR

Gliclazide 30 3.95

Euglodin Glibenclamide 5 4.00

Glazide Gliclazide 80 4.00

Euglotab Glibenclamide 5 4.50

Zebet Gliclazide 80 4.50

Glicla Gliclazide 30 5.00

Gliget MR Gliclazide 30 5.45

Daonil Glibenclamide 5 5.48

Getz Gliclazide 30 6.00

Clibite Gliclazide 80 6.00

Allase Glibenclamide 5 6.09

Orabetic Glibenclamide 5 6.16

Gluconil Gliclazide 80 6.28

BRAND NAME

GENERIC STOCK DOSE

PRICE

Clizid Gliclazide 80 7.00

Gluban Glibenclamide

5 7.00

Glubitor Gliclazide 80 7.08

Glimax Glipizide 5 7.43

Dianorm Gliclazide 80 7.62

Brilizid Glipizide 5 7.80

Diaberid Glimepiride 2 8.00

Lodulce Glibenclamide

5 8.00

Rimepril Glimepiride 2 9.00

Diamicron Gliclazide 80 9.10

Diamicron MR

Gliclazide 30 9.10

Acotril Glimepiride 2 9.61

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SULFONYLUREASBRAND NAME

GENERIC NAME

STOCK DOSE

PRICE

Arya Glimepiride 2 9.90

Aforglim 2 Glimepiride 2 9.96

Neoglim Glimepiride 2 10.50

Euglucon Glibenclamide 5 10.81

Glipiren Glimepiride 2 11.83

Euglim Glimepiride 2 12.00

Glimesyn Glimepiride 2 12.00

Diaglim Glimepiride 2 12.33

Glimed Glimepiride 2 14.00

Getryl Glimepiride 2 14.15

Winthrop Glimepiride 2 14.60

Azulix Glimepiride 2 15.00

Glimarex Glimepiride 2 15.00

Mira Glimepiride 2 15.00

Norizec Glimepiride 2 15.11

BRAND NAME

GENERIC STOCK DOSE

PRICE

Sulfast Glimepiride 2 15.40

Amara 4 Glimepiride 4 15.75

Soladin Glimepiride 2 16.00

Minidiab Glipizide 5 19.35

Solosa Glimepiride 2 21.93

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MEGLITINIDES• Efficacy:

HbA1c• 0.5-1.5%• 5.5-16.5 mmol/mol

FPG• 20-60 mg/dl• 1.1-3.3 mmol/mol

PPG• 75-100 mg/dl• 4.2-5.6 mmol/mol

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MEGLITINIDES

SIDE EFFECTS CONTRAINDICATIONS DRUG INTERACTION

Hypoglycemia (less)Weight gain

DKAT1DMPregnancy and Lactation

NSAIDsSalicylatesMAOIsNonselective β-blockersThiazidesCorticosteroidsThyroid preparationSympathomimeticsOral antidiabetic agentsCYP2C9 inhibitors

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MEGLITINIDES

BRAND NAME

GENERIC NAME

STOCK DOSE

PRICE

Novonorm Repaglinide 0.5 15.67

Starlix Nateglinide 120 31.27

• Nateglinide: Starlix 120mg/tab TID• Repaglinide Novonorm 0.5,1.2mg- TID

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ALPHA-GLUCOSIDASE INHIBITORS• Efficacy:

HbA1c• 0.5-1%• 5.5-11 mmol/mol

FPG• 10-20 mg/dl• 0.5-1.1 mmol/mol

PPG• 40-50 mg/dl• 2.2-2.8 mmol/mol

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ALPHA-GLUCOSIDASE INHIBITORS

SIDE EFFECTS CONTRAINDICATIONS DRUG INTERACTION

FlatulenceAbdominal discomfort

Chronic intestinal disorders associated w/ distinct disturbances of digestion & absorption, conditions which may deteriorate as a result of increased intestinal gas formation. Patients w/ CrCl <25 mL/min/1.73 mL, hepatic impairment. Pregnancy & lactation. Patients <18 yr.

Cholestyramine, intestinal absorbents & digestive enzymes may attenuate its effect

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ALPHA-GLUCOSIDASE INHIBITORS

BRAND NAME

GENERIC NAME

STOCK DOSE

PRICE

Basen Voglibose 0.2 12.35

Glucobay Acarbose 50 12.96

• Acarbose: 50, 100mg/tab, TID• Miglitol (glyset) – NA• Voglibose (Basen)- 0.2-0.3 mg/ TID

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THIAZOLIDINEDIONES• Increase the sensitivity of muscle and

adipose cells to insulin and suppressing hepatic glucose production

• Inhibit hepatic gluconeogenesis• Stabilize beta cell dysfunction• Efficacy:

HbA1c• 0.5-1.5%• 5.5-16.5 mmol/mol

FPG• 20-55 mg/dl• 1.1-3.1 mmol/mol

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THIAZOLIDINEDIONESSIDE EFFECTS CONTRAINDICATIONS DRUG INTERACTION

Weight gainEdemaRisk of fractures

Patients with abnormal liver functionCHF patients

Other antidiabetic agentsβ-blockersSalicylic acid preparationMAOIsFibrate derivativesWarfarinEpinephrineAdrenocortical & thyroid hormoneCYP2C8 inducer eg rifampicin & inhibitor eg gemfibrozil

• Pioglitazone - 15mg, 30mg/tab, OD• Rosiglitazone - not available – inc risk for CVD• Troglitazone (Rezulin), which was withdrawn from the market

due to an increased incidence of drug-induced hepatitis.

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THIAZOLIDINEDIONES

BRAND NAME

GENERIC NAME

STOCK DOSE

PRICE

Pioglon Pioglitazone 15 3.50

Insulact Pioglitazone 15 14.18

Prialta Pioglitazone 15 15.88

Glitaz Pioglitazone 15 15.92

Piozone Pioglitazone 15 16.98

Diabetone Pioglitazone 15 17.25

Zolid Pioglitazone 15 17.75

Ppar Pioglitazone 30 18.00

Piozar Pioglitazone 30 18.50

Actos Pioglitazone 15 67.58

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DPP-4 INHIBITORS• Efficacy:

HbA1c• 0.5-1%• 5.5-11 mmol/mol

FPG• 20 mg/dl• 1.1 mmol/mol

PPG• 45-55 mg/dl• 2.5-3.1 mmol/mol

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DPP-4 INHIBITORS

SIDE EFFECTS CONTRAINDICATIONS DRUG INTERACTION

Generally well toleratedLow risk of hypoglycemiaNot associated with weight gainUpper respiratory tract infection has been reported in clinical studies

Type 1 DMDiabetic ketoacidosis

DigoxinCyclosporine

• Sitagliptin (Januvia): 25, 50,100mg/film coated tab – OD

• Vildagliptin (Galvus): 50mg/tab OD-BID• Saxaglitpin (Onglyza): 2.5, 5mg OD• Linagliptin (Trajenta): 5mg OD

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DPP-4 INHIBITORS

BRAND NAME

GENERIC NAME

STOCK DOSE

PRICE

Galvus Vildagliptin 50 27.15

Onglyza Saxagliptin 5 52.04

Trajenta Linagliptin 5 52.07

Januvia Sitagliptin 25, 50, 100

52.14

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Glucagon-like Peptide 1 agonist

• Aka incretin mimetics

• is an insulin secretagogue, with glucoregulatory effects.

• for patients whose diabetes was not well-controlled on other oral medications.

Page 139: Diabetes Mellitus CPG

GLUCAGON-LIKE PEPTIDE 1 AGONISTS

• Efficacy:

HbA1c• 1-2%• 11-22 mmol/mol

FPG• 5.76-11.7 mg/dl• 0.32-0.65 mmol/mol

PPG• 6.12-17.28 mg/dl• 0.34-0.96 mmol/mol

Page 140: Diabetes Mellitus CPG

GLUCAGON-LIKE PEPTIDE 1 AGONISTS

SIDE EFFECTS CONTRAINDICATIONS DRUG INTERACTION

Moderate and transient nausea, vomiting and diarrheaLow risk of hypoglycemia and no evidence of increased CV risk

Not for type 1 DM or diabetic ketoacidosis. Do not use in end-stage renal disease or severe renal impairment (<30 mL/min), severe GI disease

May increase hypoglycemia when used w/ a sulfonylurea. OC, antibiotics, warfarin

Exenatide (Byetta): 250mcg/mL – 5mcg/dose bid SCLiraglutide (Victoza): 6mg/mL , 3mL – 0.6ml SC daily

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COMBINATION THERAPYBRAND NAME GENERIC NAME STOCK

DOSEPRICE

Azulix MF Glimepiride + Metformin 1+500 8.00

Euglo Plus Glibenclamide + Metformin 2.5+400 9.28

Glimet Glimepiride + Metformin 2+500 14.00

Zolid Plus Pioglitazone + Meformin 15+500 16.98

Pioplus Pioglitazone + Meformin 15+500 16.98

Prialta-Met Pioglitazone + Meformin 15+500 17.57

Solozamet Glimepiride + Metformin 2 +500 21.93

Zoliget Pioglitazone + Glimepiride 30+2 24.55

Galvusmet Metformin + Vildagliptin 500+50 28.18

Janumet Sitagliptin + Metformin 50+500 28.57

Velmetia Sitagliptin + Metformin 50+500 29.43

Actosmet Pioglitazone + Metformin 15+850 33.93

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INSULIN THERAPY

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Insulin Therapy

• Characteristics

Onset is the length of time before insulin reaches the bloodstream and begins lowering blood glucose.

Peaktime is the time during which insulin is at maximum strength in terms of lowering blood glucose.

Duration is how long insulin continues to lower blood glucose.

Page 146: Diabetes Mellitus CPG

INSULIN

• Insulin Therapy Indicationso Short-Term Use:

Acute illness, surgery, stress and emergencies

Pregnancy Breast-feedingInsulin may be used as initial therapy in type

2 diabetes in marked hyperglycaemia Severe metabolic decompensation (diabetic

ketoacidosis, hyperosmolar nonketotic coma, lactic acidosis, severe hypertriglyceridaemia)

Page 147: Diabetes Mellitus CPG

INSULIN

• Insulin Therapyo Long-Term Use:

If targets have not been reached after optimal dose of combination therapy or BIDS, consider change to multi-dose insulin therapy. When initiating this, insulin secretagogues should be stopped and insulin sensitisers e.g. Metformin or TZDs, can be continued.

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Dosing: 0.3 – 1.5/kg BW

• Rapid-acting Insulin: Lispro 100IU/ml 3mL (P705.00/cartridge or pen); aspart 100IU/ml 3mL (P724.00/pen): immediately before meals

• Short-acting: Humulin-R 100IU/mL, 3mL vial (P1,200): 30 mins before meals

• Intermediate-acting: Humulin-N 100IU/mL, 3mL (P526.00/cartridge): AM and PM

• Long-acting: glargine 100IU/mL, 10mL (P2303.00/vial); detemir 100IU/mL, 3ml (P844.00/pen) PM or bedtime

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Pre-mixed

• Humulin 70/30 (70% NPH – 30% regular insulin) Combination of int. acting + SA

• Novomix 30 (70% aspart protamine 30% aspart )

• Humalog mix 25 (75% lispro protamine, 25% lispro)

Page 152: Diabetes Mellitus CPG

Insulin Regimen

To augment beta cell function (0.3 U/kg) – prevents gluconeogenesis during bedtime

BIDS (Bedtime Insulin dailytime SU) Example: Gliclazide 80mg OD + Humulin

N 10U SC at bedtime

To replace beta cell function (0.6-1.0 U/kg) – basal and meal-related (bolus) requirements

Split dose 2/3 – 1/3 rule given before breakfast/dinner respectively

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- Split-mixed: Insulatard (int.) 20U + Actrapid (S.A) 6U before breakfast then Insulatard (int.) 10U + Actrapid (S.A) 6U before dinner

- Modified split-mixed: Humulin N 16U (intermediate acting) + Humulin R 4 U (short acting) before breakfast then Humulin R 6 U at lunch then Humulin N 8U (intermediate acting) + Humulin R 4 U (short acting) before dinner

- Basal plus Regimen: Lantus 20U (basal insulin) OD + Humalog (S.A) 10U before lunch

Page 154: Diabetes Mellitus CPG

- Basal Bolus Regimen: Pre-meal SA + basal insulin i.e., Actrapid 10U SC premeals TID + Humulin N 20U at bedtime

Page 155: Diabetes Mellitus CPG

TREATMENT ALGORITHM FOR PEOPLE WITH T2DM (IDF)

Page 156: Diabetes Mellitus CPG

QUESTIONS???

Page 157: Diabetes Mellitus CPG

THANK YOU!