DIABETES MELLITUS

IKA HUDAYANI
POLEWALI PUBLIC HOSPITAL
POLMAN

OUTLINE

Definition
Epidemiology
Pathophysiology
Diagnosis Criteria
Management
Complication

Definition
Group of metabolic
diseases characterized
by hyperglycemia
resulting from defects
in insulin secretion,
insulin action, or both

Classification

Type 1
Type 2
Gestational DM
DM associated
with other
conditions/
syndrome

Epidemiology
In 2030, DM prevalence in Indonesia reached 21.3
million people (Diabetes Care, 2004)
Riskesdas 2007:

cause of death due to DM in 45-54 yrs age group : 2 nd rank

in urban areas (14.7%) & 6th rank in rural areas (5.8%)

ST
OP
DIABET
ES

Regulation of Insulin
Secretion
Intracellular transport of
glucose is mediated by
GLUT-2 (insulin-independent
glucose transporter in cells)
Glucose undergoes oxidative
metabolism in the -cells to yield
ATP
ATP inhibits an inward K+ channel
receptor
Inhibition of this receptor leads to
membrane depolarization, influx of
Ca2+ ions, and release of stored
insulin from -cells

Metabolic actions of insulin in striated

muscle, adipose tissue, and liver

Glucose
uptake

Lipogenesis
Lipolysis

Striated
muscle
Glucose
uptake
Glycogen
synthesis

Adipose
tissue

Insulin

Liver

Gluconeogenesi
s
Glycogen
synthesis

Insulin action on a
target cell

MAP kinase: mitogen-activated protein kinase pathway for insulin &insulin-like growth
factor (mitogenic=proliferation)
PI-3K: phosphatidylinositol-3-kinase (Metabolic activity)

Pathogenesis of T2D
Much less in knownmultifactorial complex disease
1) Environmental factors, such as a sedentary life style
and dietary habits
2) Genetic factors are also involved:
Concordance rate of 35-60% in monozygotic twins
Risk for T2D in an offspring is more than double if both
parents are affected
No HLA association or autoimmune reaction

Insulin resistance & -cell dysfunction

are core defects of type 2 diabetes
Genetic
susceptibility,
obesity,
Western
lifestyle
Insulin
resistance

IR

-cell
dysfunction

Type 2 diabetes
Rhodes CJ & White MF. Eur J Clin Invest 2002; 32
(Suppl. 3):313.

Insulin resistance reduced

response to circulating insulin
Insulin
resistance

Liver

Glucose output

IR
Adipose
tissue

Muscle

Glucose uptake

Glucose uptake

Hyperglycemia

Why does the -cell fail?

Oversecretion of
insulin to
compensate for
insulin resistance1,2

Glucotoxicity2

Chronic
hyperglycemi
a

Lipotoxicity3

Pancrea
s

High
circulating
free fatty acids

-cell
dysfunction
Boden G & Shulman GI. Eur J Clin Invest 2002; 32:1423.
Kaiser N, et al. J Pediatr Endocrinol Metab 2003; 16:522.
3
Finegood DT & Topp B. Diabetes Obes Metab 2001; 3 (Suppl.
1

Clinical Manifestations
3 Ps: polyuria,
polydipsia, & polyphagia
Fatigue & weakness
Sudden vision changes
Tingling or numbness in
hands/feet
Dry skin
Skin lesions/wounds that
are slow to heal
Recurrent infections

Diagnostic Criteria
A1C 6.5%
OR

Fasting plasma glucose (FPG) 126

mg/dL (7.0 mmol/L)
OR

2-h plasma glucose 200 mg/dL

(11.1 mmol/L) during an OGTT
OR

A random plasma glucose 200

mg/dL (11.1 mmol/L)
ADA. Classification and Diagnosis. Diabetes Care 2013;36(suppl 1):S13; Table 2.

 A1C : The test should be performed in

a laboratory using a method that is
NGSP certified and standardized to
the DCCT assay*
Fasting is defined as no caloric intake
for at least 8 h*
OGTT : The test should be performed
as described by the WHO, using a
glucose load containing the
equivalent of 75 g anhydrous glucose
dissolved in water*
*In the absence of unequivocal hyperglycemia, result should be confirmed by repeat
testing.
ADA. Classification and Diagnosis. Diabetes Care 2013;36(suppl 1):S13; Table 2.

Prediabetes : IFG, IGT,

Increased A1C
FPG 100125 mg/dL (5.66.9
mmol/L): IFG
OR

2-h plasma glucose in the 75-g OGTT

140199 mg/dL (7.811.0 mmol/L):
IGT
OR

A1C 5.76.4%

*For all three tests, risk is continuous, extending below the lower limit of a range and
becoming disproportionately greater at higher ends of the range.

ADA. Classification and Diagnosis. Diabetes Care 2013;36(suppl 1):S13; Table 3.

Criteria for Testing for

Diabetes in
Asymptomatic Adult
1.Testing should be considered in all adults
Individuals
who are overweight (BMI 25 kg/m *) and
2

have
additional
risk factors:
Physical
HDL cholesterol level <35
inactivity
mg/dL (0.90 mmol/L) and/or a
First-degree relative with
TG level >250 mg/dL (2.82
diabetes
mmol/L)
High-risk race/ethnicity (e.g.,
Women with polycystic ovary
African American, Latino,
syndrome (PCOS)
Native American, Asian
A1C 5.7%, IGT, or IFG on
American, Pacific Islander)
previous testing
Women who delivered a
baby weighing >9 lb or were Other clinical conditions
diagnosed with GDM
associated with insulin
resistance (e.g., severe
Hypertension (140/90
*At-risk
BMI may
lower
in somefor
ethnic groups.obesity, acanthosis nigricans)
mmHg
orbeon
therapy
History of CVD
hypertension)

ADA. Testing for Diabetes in Asymptomatic Patients. Diabetes Care 2013;36(suppl 1):S14; Table 4.

2. In the absence of criteria (risk

factors on previous slide), testing for
diabetes should begin at age 45
years
3. If results are normal, testing should
be repeated at least at 3-year
intervals, with consideration of more
frequent testing depending on initial
results (e.g., those with prediabetes
should be tested yearly), and risk
status
ADA. Testing for Diabetes in Asymptomatic Patients. Diabetes Care 2013;36(suppl 1):S14; Table 4.

Management

Education
The purpose of education in DM
Supports the efforts of diabetics to understand the
natural history of the disease & its management
Recognize health problems / complications that may
arise
Adherence monitoring and management of disease
independently (SMBG)
Changes in behavior / health habits

Medical Nutritional
Therapy
Individuals who have prediabetes or diabetes
should receive individualized MNT as needed to
achieve treatment goals, preferably provided by
a registered dietitian familiar with the
components of diabetes MNT

ADA. Diabetes Care. Diabetes Care 2013;36(suppl 1):S22.

 Weight loss (overweight/obese) and weight

maintenance
Use of low carbohydrate, low fat calorie-restricted, or
Mediterranean diet
Monitor lipids, renal function, and protein intake
Individual diet plan for intake of carbohydrates,
proteins, and fats
Saturated fat < 7 % of total calories (9 calories per
gram of fat); limit trans fats
Addition of physical activity (design to meet patients
ability)
Increase intake of whole grains to get recommended
daily intake for fiber
Limit alcohol intake to moderate (1 drink per day
women; 2 per day men)
Specific vitamin supplementation not currently
supported by evidence
ADA. Standards of medical care in diabetes - 2013. Diabetes Care. 2013;36(1): S11-S66

Exercise
Regular physical exercise 3-4 times a week for
30 minutes
Aerobic such as walking, jogging, cycling, and
swimming
To maintain fitness and lose weight and improve
insulin sensitivity

Primary sites of action of oral

antidiabetic agents
-glucosidase
inhibitors

Sulfonylureas/
meglitinides

Biguanides

Carbohydrate
breakdown/
absorption

Insulin
secretion

Glucose output
Insulin resistance

Thiazolidinediones

Insulin
resistance

Kobayashi M. Diabetes Obes Metab 1999; 1 (Suppl. 1):S32S40.

Nattrass M & Bailey CJ. Baillieres Best Pract Res Clin Endocrinol
Metab 1999; 13:309329.

Medications for DM:

Biguanides - Metformin (Glucophage)

decrease hepatic glucose output - weight neutral or mild

loss, no hypoglycemia, cheap - GI side effects,
contraindicated in CRI and unstable CHF because of risk of
lactic acidosis, B12 deficiency

Sulfonylureas - Glipizide (Glucotrol), glimeperide

(Amaryl)
enhance insulin secretion - cheap - weight gain,
hypoglycemia

Insulins - Lispro (Humalog), aspart (Novolog),

glulisine (Apidra); Regular; NPH; glargine (Lantus),
detemir (Levemir); and fixed combinations

no dose limit, NPH and Regular are cheap, improve lipids injections, weight gain, hypoglycemia, analogs are
expensive

 Thiazolidinediones (TZDs or Glitazones) Pioglitazone (Actos)

increase sensitivity to insulin - improve lipids, potential

decrease in MI, no hypoglycemia - fluid retention, weight gain,
CHF, fractures, expensive, ?bladder cancer (taken off of market
in France and Germany)

DPP-4 Inhibitors - Sitagliptin (Januvia), saxagliptan

(Onglyza), linagliptin (Tradjenta), alogliptin (Nesina)

increase glucose-mediated insulin secretion, suppress glucagon

secretion - weight neutral, no hypoglycemia - expensive, ?
effects on immune system/pancreatitis/pancreatic cancer, long
term effects not known

GLP-1 Agonists (Incretin Mimetics) - Exenatide

(Byetta, Bydureon), liraglutide (Victoza)

potentiate glucose-stimulated insulin secretion, suppress

glucagon secretion, slow gastric motility - weight loss, ?
delay/prevention of beta cell failure, no hypoglycemia injections, expensive, GI side effects, ?pancreatitis/pancreatic
cancer, ?medullary CA of the thyroid, long term effects not
known.

 -Glucosidase Inhibitors - Acarbose (Precose)

reduce the rate of digestion of polysaccharides - weight neutral, no
hypoglycemia - severe GI side effects, expensive, three times daily

Glinides - Nateglinide (Starlix), repaglinide

(Prandin)

stimulate insulin secretion - weight gain, three times daily, expensive,

hypoglycemia

Amylin Agonists - Pramlintide (Symlin)

slow gastric emptying, decrease glucagon secretion - weight loss, no

hypoglycemia - injections, expensive, GI side effects, long term effects
not known

Bile Acid Resins - Colesevelam (WelChol)

mechanism of action unknown

Dopamine Receptor Agonists - Bromocriptine

(Cycloset)
mechanism of action unknown, but probably normalizes aberrant
hypothalamic neurotransmitter activities

Sodium-glucose Transporter-2 Inhibitors

(SGLT2s) - Canagliflozin (Invokana)
block reabsorption of glucose in the kidneys

Updated PERKENI Type 2 Diabetes

Treatment Algorithm
Diabetes

STEP 1

Healthy life style

Note:
1. Therapy failed if
target of HbA1c
< 7% is not
achieved within
2-3 months for
each step
2. In case of no
HbA1c test, the
use of blood
glucose level is
also permitted.
Average blood
glucose level for
a few BG test in
one day can be
converted to
HbA1c (ref: ADA
2010)

Healthy life
style
+
Mono therapy

STEP 2

Healthy life
style
+
2 OAD
Combination

Alternative option, if :
No insulin is available
The patient is objecting insulin
Blood glucose is still not
optimally controlled

Healthy life
style
+
3 OAD
Combination

STEP 3

Healthy life
style
+
Combination 2
OAD
+
Basal insulin

Insulin
Intensification*

*Intensive Insulin: use of basal insulin together with insulin prandial

Glycemic Recommendations for

Nonpregnant Adults with Diabetes
A1C
Preprandial capillary
plasma glucose
Peak postprandial
capillary plasma
glucose

<7.0%*
70130 mg/dL*
(3.97.2 mmol/L)
<180 mg/dL*
(<10.0 mmol/L)

*Individualize goals based on these values.

Postprandial glucose measurements should be made 12 h after the beginning of the
meal, generally peak levels in patients with diabetes.
ADA. Diabetes Care. Diabetes Care 2013;36(suppl 1):S21; Table 9.

The benefits of good

blood glucose control are
clear
Myocardial

Good control is
7.0% HbA1c

infarction

HbA1c measures
the average blood
glucose level over
the last 3 months HbA1c

-1%

-14%
Microvascular
complications

-37%
Deaths related
to diabetes

-21%
Source: UKPDS = United Kingdom Prospective Diabetes Study.
Stratton IM et al. BMJ. 2000;321(7258):405-412.

 Goals should be individualized based on

Duration of diabetes
Age/life expectancy
Comorbid conditions
Known CVD or advanced microvascular
complications
Hypoglycemia unawareness
Individual patient considerations

More/less stringent glycemic goals may

be appropriate for individual patients
Postprandial glucose may be targeted if
A1C goals are not met despite reaching
preprandial glucose goals

Microvascular Complications:
Nephropathy
Retinopathy
Neuropathy
Foot
ulcers/lesions
Numbness,
pain
Sexual
dysfunction
Gastroparesis

Macrovascular Complications
Cardiovascular
Diseases (CVD)
Coronary Artery
Disease (CAD)
Myocardial
Infarction (MI)
Stroke or
transient
ischemic attack
(TIA)
Peripheral Artery
Disease (PAD)

Acute Complications of
Diabetes
Hypoglycemia50-60 or less
DKA
HHNS

Hypoglycemia
Caused by too much insulin or oral agents, too
little food or excessive physical activity
Surge in epinephrine and norepinephrine
results in sweating, tremors, tachycardia,
palpitations, nervousness and hunger
CNS effectsinability to concentrate, headache,
lightheadedness, confusion, memory problems,
slurred speech, incoordination, double vision,
seizures and even loss of consciousness

Hypoglycemic
unawareness
Related to autonomic neuropathy
Will not experience the sympathetic surgewith
sweating, shakiness, HA, etc

Treatment for
hypoglycemia

2-3 tsp. of sugar or honey

6-10 hard candies
4-6oz. of fruit juice or soda
3-4 commercially prepared glucose tablets
Recheck BS 15 minutes, same s/s, repeat treatment.
After improvement, then cheese and crackers or milk.
Extreme situations, give glucagon. (can cause n/v).
D50W.

Diabetic Ketoacidosis
Clinical features:
1. Hyperglycemia
2. Dehydration and electrolyte
loss
3. Acidosis
3 main causes: illness, undiagnosed & untreated
and decreased insulin
Other causes: patient error, intentional skipping of
insulin

Presentation of DKA

3 Ps
Orthostatic hypotension
Ketosis
GI s/s
Acetone breath
hyperventilation

Diagnostic Findings of
DKA

BS between 300-800
Acidosis
Electrolyte abnormalities
Elevated BUN, creatinine and hct r/t dehydration

Medical Management
of DKA
Rehydrate with normal saline, then follow with .
45% NaCl then D5.45NS (or other)
Restore electrolytes
ECGs
Hourly blood sugars
IV insulin
Avoid bicarbonate as can affect serum K+

Hyperglycemic Hyperosmolar
Nonketotic Syndrome
Predominated by hyperosmolarity and
hyperglycemia
Minimal ketosis
Osmotic diuresis
Glycosuria and increased osmolarity
Occurs over time
Blood sugar is usually over 600

HHNS

Occurs more often in older people

Type 2 diabetes mellitus
No ketosis
Do not usually have the concomitant n/v
Hyperglycemia, dehydration and
hyperosmolarity may be more severe than in
DKA

Medical Management
Similar treatment as seen in DKA
Watch fluid resuscitation if history of heart
failure
ECG
Lytes monitoring
Fluids with potassium replacement

Thank you
for your
attention