CLINICAL PRACTICE

GUIDELINES FOR THE

DIAGNOSIS AND MANAGEMENT
OF DIABETES MELLITUS
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
DIABETES MELLITUS

Complex metabolic disorder characterized by

persistent hyperglycemia resulting from:
o Reduced insulin secretion
o Decreased glucose utilization
o Increased glucose production
CLASSIFICATION OF
DIABETES MELLITUS
Type 1 Diabetes (insulin-dependent/ Juvenile

DM)
o Complete or near-total insulin deficiency
o Caused by the autoimmune destruction of
-cells of the pancreatic islets
o May be idiopathic
Type 2 Diabetes (noninsulin-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
DIFFERENTIATION
BETWEEN TYPE 1 AND
TYPE 2 DM
 DEFINITION OF
DIABETES
TEST
MELLITUS
WHO ADA Philippi AACE IDF
ne CPG
Fasting
Plasma 126 mg/dL (7.0 mmol/L)
Glucose
2-h
Plasma
Glucose 200 mg/dL (11.1 mmol/L)
after 75-g
OGTT
HbA1c 6.5%
Random
Plasma 200 mg/dL (11.1 mmol/L) + symptoms
PRE-DIABETES

Impaired Fasting Glucose

o FPG of 100125 mg/dL (5.66.9 mmol/L) ADA, AACE,
Phil. CPG

o FPG of 110125 mg/dL (6.16.9 mmol/L) WHO:

Impaired Glucose Tolerance

o 2h 75-g OGTT of 140199 mg/dL (7.811.0
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

Diabetes mellitus in
the ADULT AND THE
ELDERLY

SOURCES:
AMERICAN DIABETES ASSOCIATION CPG ON DM, 2013
UNITE PHILIPPINES CPG ON DM
SCREENING

All individuals being seen at any physicians

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)
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)
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)
SCREENING

If initial test/s are negative for diabetes, repeat

testing should ideally be done annually. (Grade
D, Level 5)
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 fast
o Two-hour plasma glucose > 200 mg/dl (11.1
mmol/l) during an Oral Glucose Tolerance
Test
o 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.
DIAGNOSIS

*Among ASYMPTOMATIC individuals with

positive results, any of the three tests should be
REPEATED within two weeks for confirmation.
(Grade C, Level 4)
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
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)
DIAGNOSIS

We do not recommend the following tests for

the diagnosis of diabetes (Grade B, Level 3):
o Urine glucose
o Plasma Insulin
MANAGEMENT AND
MONITORING
Initial evaluation - comprehensive medical
history and PE
o Coronary heart disease risk assessment
o Foot evaluation: assess risk for foot ulcer
(identify high-risk feet)
o Eye exam: fundoscopy on diagnosis
o Dental history or oral health history
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
 GLUCOSE CONTROL
IDF AACE ADA
HBA1c 6.5% 6.5% < 7%
Preprandial < 110 < 110 70-130
plasma glucose mg/dL mg/dL mg/dL
Peak NA < 140 < 180
postprandial mg/dL mg/dL
glucose
Bedtime plasma NA NA 110-150
glucose mg/dL
*Goals should be individualized
*Certain populations require special
considerations
*Less intensive glycemic goals may be
MANAGEMENT AND
MONITORING
Glycemic targets
should be achieved
within 6 months of
diagnosis or first
prescription.
MANAGEMENT

The major components of the treatment of

diabetes are:
Diet and
A Exercise

Oral
B hypoglycaemic
therapy

C Insulin Therapy
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
MANAGEMENT AND
MONITORING
Initiate treatment with metformin for
monotherapy unless with contraindications or
intolerance of its ADEs
o Diarrhea
o Severe nausea
o Abdominal pain
MANAGEMENT AND
MONITORING
When optimization of therapy is needed, choose
the second drug according to the following -
o Degree of HbA1c lowering
o Hypoglycemia risk
o Weight gain/loss
o Patient profile (dosing complexity, renal/hepatic
problems, other contraindications and age)
Sequence of Antihyperglycemic Therapy (ADA, 2012)
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 (?)

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
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.
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
MANAGEMENT AND
MONITORING
Statin therapy should be added to lifestyle therapy,
regardless of baseline levels for diabetics
o 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)
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]
MANAGEMENT AND
MONITORING
Insufficient evidence to recommend aspirin for
primary prevention in lower risk individuals
o Men < 50 y
o Women <60 y

Clinical judgment if with multiple risk factors

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].
 LIPID PROFILE, BLOOD
PRESSURE AND BMI
Parameter Ideal Acceptable Bad
TGTARGET <1.5 mmol/L <2.2mmol/L > 2.2
(150 mg/dl) mmol/L
TC < 4.5mmol/L >4.5 mmol/L > 6.0
(200 mg/dl) mmol/L
LDL < 2.5 mmol/L (100 < 4.4mmol/L > 4.4
mg/dl) mmol/L
HDL > 1.1 mmol/L 0.9- < 0.9
(40 mg/dl in men; 50 1.1mmol/L mmol/L
mg/dl in women)
BP < 130/80mmHg >130/80- > 140/90
<140/90
BMI (Males) < 25 <27 27
BMI < 24 <26 26
MANAGEMENT AND
MONITORING
The following patients must be referred to
internists or diabetes specialists
(endocrinologists or diabetologists) -
o Type 1 diabetes
o Moderate to severe hyperglycemia
o Co-morbid conditions (infections, acute CV events
i.e. CHF or acute MI)
o Significant hepatic and renal impairment
o Women with diabetes who are pregnant
Pharmacology of
anti-diabetic drugs
Sequence of Antihyperglycemic Therapy (ADA, 2012)
Oral hypoglycemic
agents
 There are currently six classes of oral anti-
diabetic agents:
Biguanides
Insulin Secretagogues Sulphonylureas
Insulin Secretagogues Non-
sulphonylureas
-glucosidase inhibitors
Thiazolidinediones (TZDs)
DPP-IV Inhibitors
 Drug Class Agents Mechanism of Action
Alpha-glucosidase Acarbose Delay intestinal
inhibitors Voglibose carbohydrate absorption
Hepatic glucose
production
Biguanides Metformin
Liver and muscle
insulin sensitivity
Glimepiride
Insulin Glipizide
secretagogues Glyclazide insulin secretion
sulfonylureas Glibenclamide
(glyburide)
Insulin
Nateglinide,
secretagogues insulin secretion
Repaglinide
Meglitinides
Postrandial insulin
Sitagliptin
secretion,
DPP-IV Inhibitors Vildagliptin
glucagon secretion,
Saxagliptin
Delay gastric emptying
Pioglitazone Adipose and muscle
Thiazolidinediones
Rosiglitazone insulin sensitivity
Biguanide:
METFORMIN
Primary effects are to decrease hepatic

glucose production and increase insulin-
mediated peripheral glucose uptake
Efficacy:

HbA1c FPG
1-2% 40-70 mg/dl
11-22 mmol/mol 2.2-3.9 mmol/mol
METFORMIN
SIDE EFFECTS CONTRAINDICATIO DRUG Preparation
NS
INTERACTION
Lactic acidosis Kidney failure Cimetidine Tablets: 500,
(rare; in patients Liver disease Furosemide 850, and 1000
with CHF) Lactic acidosis Nifedipine mg. Tablets
Diarrhea and (extended
abdominal release): 500,
discomfort 750, and 1000
Weight loss 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
METFORMIN
BRAND STOC PRICE BRAND STOCK PRICE
NAME K NAME DOSE
DOSE Melta-SE 500 6.00
RiteMed 500 3.09 Neomet 500 6.00
Gludin 500 3.20 Panfor SR 500 6.50
Neoform 500 3.35 Ansures 500 7.00
Diamet 500 3.50 MR
500 Glumet 500 7.22
Pharex 500 3.75 Fornidd 500 7.40
Nidcor 500 4.32 Euform 850 8.90
Winthrop 500 4.50 Retard
Diafat 500 5.19 Humamet 500 9.40
Glucofor 500 5.60 Glucophag 500,
m e 750, 850
I-Max 500 5.60
Secretagogues

These medications try to

replace the natural
stimulus for beta cells to
secrete insulin.
SULFONYLUREAS
Efficacy:

HbA1c FPG
1-2% 40-70 mg/dl
11-22 mmol/mol 2.2-3.9 mmol/mol

Short-acting:
o Tolbutamide
Intermediate-acting:
o Tolazamide
o Glipizide
o Glyburide/ Glibenclamide
Long-acting:
o Chloropropamide
o Glimepiride
 SULFONYLUREAS
SIDE EFFECTS CONTRAINDICATION DRUG INTERACTION
S
Hypoglycemia IDDM (next slide)
Weight gain DKA
Diabetic Coma
Pregnancy, Lactation
Short-acting:
o Tolbutamide: not available
Intermediate-acting:
o Tolazamide: not available
o Glipizide: Minidiab 5,10mg OD max: 40mg/d
o Glyburide/ Glibenclamide: Daonil 5mg Maintenance: 5-10 mg/day
Long-acting:
o Chloropropamide: not available
o Glimepiride: Aforglim 2, 3 mg OD
o Glicazide: Diamicron 30, 80mg OD
ALPHA-GLUCOSIDASE
INHIBITORS
Efficacy:

HbA1c FPG
0.5-1% 10-20 mg/dl
5.5-11 mmol/mol 0.5-1.1 mmol/mol

PPG
40-50 mg/dl
2.2-2.8 mmol/mol
 ALPHA-GLUCOSIDASE
INHIBITORS
SIDE EFFECTS CONTRAINDICATION DRUG INTERACTION
S
Flatulence Chronic intestinal Cholestyramine,
Abdominal discomfort disorders associated w/ intestinal absorbents &
distinct disturbances of digestive enzymes
digestion & absorption, may attenuate its
conditions which may effect
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.
THIAZOLIDINEDION
ES
Increase the sensitivity of muscle and adipose cells to
insulin and suppressing hepatic glucose production
Inhibit hepatic gluconeogenesis
Stabilize beta cell dysfunction
Efficacy:

HbA1c FPG
0.5-1.5% 20-55 mg/dl
5.5-16.5 mmol/mol 1.1-3.1 mmol/mol
THIAZOLIDINEDIONES
SIDE EFFECTS CONTRAINDICATION DRUG INTERACTION
S
Weight gain Patients with abnormal Other antidiabetic
Edema liver function agents
Risk of fractures CHF patients -blockers
Salicylic acid
preparation
MAOIs
Fibrate derivatives
Warfarin
Epinephrine
Adrenocortical &
thyroid hormone
CYP2C8 inducer eg
rifampicin & inhibitor
Pioglitazone - 15mg, 30mg/tab, OD
eg gemfibrozil
Rosiglitazone - not available inc risk for CVD
Troglitazone (Rezulin), which was withdrawn from the market
due to an increased incidence of drug-induced hepatitis.
DPP-4 INHIBITORS
Efficacy:

HbA1c FPG
0.5-1% 20 mg/dl
5.5-11 mmol/mol 1.1 mmol/mol

PPG
45-55 mg/dl
2.5-3.1 mmol/mol
 DPP-4 INHIBITORS
SIDE EFFECTS CONTRAINDICATION DRUG INTERACTION
S
Generally well Type 1 DM Digoxin
tolerated Diabetic ketoacidosis Cyclosporine
Low risk of
hypoglycemia
Not associated with
weight gain
Upper respiratory tract
infection has been
reported in clinical Sitagliptin (Januvia): 25, 50,100mg/film
studies
coated tab OD
Vildagliptin (Galvus): 50mg/tab OD-BID
Saxaglitpin (Onglyza): 2.5, 5mg OD
Linagliptin (Trajenta): 5mg OD
Glucagon-like Peptide
1 agonist
Aka incretin mimetics

is an insulinsecretagogue, with glucoregulatory

effects.

for patients whose diabetes was not well-

controlled on otheroral medications.
GLUCAGON-LIKE
PEPTIDE Efficacy:

1 AGONISTS
HbA1c FPG
1-2% 5.76-11.7 mg/dl
11-22 mmol/mol 0.32-0.65 mmol/mol

PPG
6.12-17.28 mg/dl
0.34-0.96 mmol/mol
GLUCAGON-LIKE
PEPTIDE 1 AGONISTS
SIDE EFFECTS CONTRAINDICATION DRUG INTERACTION
S
Moderate and Not for type 1 DM or May increase
transient nausea, diabetic ketoacidosis. hypoglycemia when
vomiting and diarrhea Do not use in end- used w/ a sulfonylurea.
Low risk of stage renal disease or OC, antibiotics,
hypoglycemia and no severe renal warfarin
evidence of increased impairment (<30
CV risk mL/min), severe GI
disease
Exenatide (Byetta): 250mcg/mL
5mcg/dose bid SC
Liraglutide (Victoza): 6mg/mL , 3mL 0.6ml
SC daily
Insulin therapy
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.
INSULIN

Insulin Therapy Indications

o Short-Term Use:
Acuteillness, surgery, stress and
emergencies
Pregnancy

Breast-feeding

Insulinmay be used as initial therapy in type

2 diabetes in marked hyperglycaemia
Severe metabolic decompensation (diabetic
ketoacidosis, hyperosmolar nonketotic coma,
lactic acidosis, severe hypertriglyceridaemia)
INSULIN

Insulin Therapy
o Long-Term Use:
Iftargets 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.
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
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)
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
 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
- Basal Bolus Regimen: Pre-meal SA + basal
insulin i.e., Actrapid 10U SC premeals TID +
Humulin N 20U at bedtime
TREATMENT
ALGORITHM FOR
PEOPLE WITH T2DM
(IDF)
Thank you!