‘Amang’ Rodriguez Memorial Medical Center

Sumulong Highway, Marikina City

Department of Internal Medicine

Type 2 Diabetes Mellitus

COMPLICATIONS
LOUIJE P. MOMBAEL
ARMMC - POST GRADUATE INTERN
OBJECTIVES:

To present a case of a type 2 DM with associated

complication

To discuss the different possible complications

associated with type 2 DM

To discuss the management of type 2 DM

complications
 GENERAL DATA:
A.B.

60 year old

Male

Filipino

Born on January 1, 1951 at Rodriguez, Rizal

Roman Catholic

Currently residing at Rodriguez, Rizal

CHIEF COMPLAINT:

“I have a horrible pain (burning-like)

sensation in my feet especially at night”
HISTORY OF PRESENT ILLNESS:
Patient is a known case of Diabetes Mellitus Type 2 &
Hypertensive Stage II for 5 years
• Sudden onset of pain (burning-like) sensation started with right foot first and then left and worsen especially at night.
• Denies any range of motion (ROM) limitations, weakness, tremors, twitching, swelling, redness or musculoskeletal trauma.
• No medications taken. No consult done
3 MONTHS
PTC

• Still with above symptom.

• No medications taken. No consult done
• Patient claims that he was not able to monitor his blood glucose levels for the past few months but his wife always monitor his blood
DURING THE pressure using the automated BP apparatus with his usual BP was ranging 130s-140s/80s-90s mmHg. He claims that he is compliant
INTERIM with his medications for diabetes and hypertension.

Persistence of
the symptom CONSULT
PAST MEDICAL HISTORY:
Diabetes mellitus (DM) for 5 year
• Sitagliptin + Metformin 50mg + 1000 mg OD

Hypertension (HTN) for 5 years

• Amlodipine / Olmesartan 5mg / 20mg OD

Denies bronchial asthma, tuberculosis, coronary artery disease (CAD), or

peripheral vascular disease. Denies any previous surgeries or hospitalization

No known allergies to food or drugs

Unrecalled childhood vaccines, No adult vaccines given

Childhood illness: patient claims that he had, mumps, chicken pox, measles.
FAMILY MEDICAL HISTORY:
Mother: 80 y/o. Apparently well, but with HTN.

Father: died at age 56 from an industrial accident.

2 brothers: 40 & 48 y/o, one with HTN and one with alcohol abuse.

Denies other heredo-familial disorder such as diabetes, asthma, tuberculosis,

coronary artery disease (CAD), peripheral vascular disease (PVD), cerebral
vascular disease (CVD), or cancer (CA).
PERSONAL AND SOCIAL HISTORY:
Smokes 1 pack per day x 20
years (20 pack years).
1-2 bottles of beer per day, up
to 3-4 bottles during occasions.
Patients diet history reveals high carbohydrate
intake in the form of bread, rice and pasta.
• Usual lunch/dinner consists of 1-2 cups rice, meat or sometimes 1-
2 servings of cooked pasta with 1-2 slices of bread.
• During the day, he often has “a slice or two” of bread with butter.
He also eats eight to ten pieces of fresh fruit per
day every after meals and during snacks.

Denies illicit drug use.

Since retired already, he has
less physical activity, he usually
does gardening.
He prefers chicken and fish, but it is usually served
with a tomato or cream sauce accompanied by rice
or pasta.
 REVIEW OF SYSTEMS
General: CVS:
​(-) chills​​ (-) tremors​​ (-) dizziness​​ (-) fever ​(-) chest pain​​ (-) dyspnea (-) easy fatigability ​(-) orthopnea​​ (-) palpitation​​ (-) syncope
​(-) malaise ​ (-) weakness​​ (-) weight loss ​ (-) fatigue ​ 
GIT:
Integumentary: ​(-) abdominal enlargement​ (-) anorexia​ (-) constipation (-) diarrhea ​(-) dysphagia​​
(​ -) dryness​​ (-) itchiness (-) jaundice​ (-) pigmentation ​(-) hematoma​​ (-) (-) flatulence ​(-) hematemesis​ (-) hematochezia ​(-) melena​​ (-) nausea​
sweating (-) sore (-) lesions/rashes
(-) steatorrhea​ (-) vomiting (-) decrease appetite
​
Head and Neck:
GUT:
​(-) head injury ​(-) lymphadenopathy​ (-) mass
​(-) discharge ​(-) dysuria (-) flank/suprapubic pain (-) frequency (-) hematuria
​(-) incontinence​ (+) nocturia​ (-) oliguria (-) passage of stone
Eyes:
(+) polyuria (-) urinary incontinence
​(-) diplopia​​ (+) corrective glasses (-) Blurring of vision (-) photophobia
​(-) lacrimation​ (-) eye pain​ (-) eye redness
Musculoskeletal:
​(-) atrophy (-) back pain​​ (-) bone deformation (-) joint pain (-) muscle pain
Ears: (-) weakness
​(-) hearing loss ​(-) tinnitus
​ Neurological:
Nose and Sinuses: ​(-) dizziness​ (-) memory loss​​ (-) seizures​ (-) syncope (-) tremors​​ (-) hallucinations
​(-) disturbance in smell (-) epistaxis (-) obstruction​ (-) pain
​ Endocrine:
Mouth: ​(-) abnormal growth​​ (-) easy fatigability​​ (-) goiter​​​(-) insomnia
​(-) disturbance of taste ​(-) sore throat (-) heat/cold intolerance (+) polydipsia ​(+) polyphagia​ (+) polyuria
​  
Respiratory: Hematological:
​(-) back pain​​ ​(-) chest pain ​(-) colds​​ ​(-) dyspnea (-) wheezes​​ (-) cough ​(-) easy bruisability ​(-) easy fatigability​​ (-) pallor
PHYSICAL EXAMINATION
GENERAL SURVEY:
The patient is awake, conscious and coherent, well groomed, alert and calm, no
slurring of speech, and cooperative. He is well nourished, with large body built and
good posture., ambulatory. Patient is afebrile and not in cardiac or respiratory
distress.

VITAL SIGNS:
BP = 130/80 mmHg PR = 82 BPM Weight = 85 kgs BMI = 30.14 kg/m2
T = 36.8 °C RR = 19 CPM Height = 168 cm (OBESE II )

INTEGUMENTARY:
The skin is brown, thick, smooth, moist with good skin turgor and mobility. No
presence of abnormal pigmentations, ecchymoses, rashes and edema noted. Upper
and lower extremities and trunk are warm to touch. Nails are clean, light pink in color,
no clubbing and no nail plate abnormalities noted. Capillary refill >3 sec.
Cont… PHYSICAL EXAMINATION
HEENT:
The cranium is normocephalic, symmetrical and has no
deformities. No tenderness and no masses. Temporal arteries
not visible but palpable with strong pulsations. Face is
symmetrical, no abnormal facies seen.
No sign of exophthalmos and enophthalmos. Anicteric sclerae,
Pink palpebral conjunctiva, no edema and no lesions. Pupils
are equal, round, and about 3mm upon constriction, reactive
to both direct and consensual reflex. Full visual fields, upon
fundoscopic examination red reflex present, no papilledema or
AV nicking noted.
External ears are symmetrical, no deformities, no lesion and no
tenderness. External auditory canal is patent, walls are pinkish,
no discharges and no foreign bodies. Intact tympanic
membrane. Rinne test: air > bone conduction bilaterally,
Weber test: midline
Nose is symmetrical. No flaring of ala nasi. Vestibule is
patent, mucosa is pinkish, with no secretions and no
bleeding. Nasal septum is at the midline. No tenderness and
clouding of Paranasal sinuses upon Trans illumination.
Lips are pinkish, dry, no lesions. Buccal mucosa is pinkish,
moist, no lesion, no swelling. Tongue is moist, no lesions,
not atrophied/hypertrophied and is not deviated. Patient is
noted to have dentures. Palate is pinkish, intact, no lesions.
Uvula is at midline, pink, no lesion and located at midline.
Tonsils are normal, pink, not swollen, no secretions.
Neck is symmetrical, has well developed muscles and has no
deviation. Trachea is in the midline. No lymphadenopathy,
No mass noted.
Cont.. PHYSICAL EXAMINATION
RESPIRATORY:
Symmetrical chest expansion, no retractions, clear breath sounds

CARDIOVASCULAR:
Adynamic precordium, no heaves nor thrills, normal rate regular rhythm, no murmur

DRE:
GASTROINTESTINAL:
No skin tags, No palpable mass, No
Flabby, normoactive bowel sounds, soft, non-tender, no palpable mass, tympanitic on all quadrants tenderness, No blood on the examining
finger noted.

EXTREMITIES:
Grossly normal extremities, no edema, no cyanosis, full and equal pulses, slight tenderness on upon
passive ROM of the both feet

GENITOURINARY:
Normal looking external genitalia, no lesions.
 Cont.. PHYSICAL EXAMINATION
Mental Status: conscious, coherent

Cerebrum:
NEUROLOGIC

Speech is normal and with appropriate content. Well oriented to time, place and
person. She was able to follow simple and complex commands and do simple
calculation. Has an intact immediate, recent and remote memory. She was able to
recognize objects and distinguished its appropriate function.

Cerebellum:
Patient was able to perform finger to nose test with no arm dysmetria noted.
Negative for dysdiadochokinesia, she was able to alternately do pronation and
supination. No dysmetria of lower extremities, she was able to perform heel to shin
test smoothly at both sides.
 Cont.. PHYSICAL EXAMINATION
Cranial Nerves:

CN 8 - The patient was able to repeat words whispered to her

CN 1 - no anosmia and able to localized sound. Sounds are equally heard on both
ears with normal neurosensory hearing and no conductive
hearing loss.
CN 2 – Pupils are 2-3 mm in diameter, equally reactive to
NEUROLOGIC

light, VA: 20/100 OU, but 20/20 OU w/ corrective glasses,

[+] ROR, no papilledema or AV nicking noted. CN 9, 10 - Gag reflex was present bilaterally, uvula is at the
midline and no hoarseness was noted.

CN 3, 4, 6 - no limitation of EOM

CN 11 - No fasciculations, tremors or atrophy noted. Patient

was able to shrug her shoulders symmetrically, flex her head,
CN 5 – Able to distinguish sharp from blunt object. He rotate head and bend laterally against resistance
was able to contract his temporals and master muscle by
clenching his teeth. (+) corneal reflex.

CN 7 - Well delineated with normal facial creases, no CN 12 - Tongue is in the midline, symmetrical when protruded.
change in sense of taste, no facial asymmetry, able to No fasciculation or involuntary movement observed.
smile, frown, blow cheeks, and close his eyes.
 Cont.. PHYSICAL EXAMINATION
Motor: No fasciculation, atrophy, and no involuntary movements. Muscles
are normotonic, 5/5 both upper and lower extremities

Sensory: No impairment on position sense, vibratory sense and pain

sensation of UE & LE (except on his both feet noted to have an increase
pain sensation)
NEUROLOGIC

Deep Tendon Reflexes: Biceps, triceps, and knee reflexes are (2+),
Decreased on ankle (1+)

Pathologic Reflexes: No Babinski

Meningeal Signs: No nuchal rigidity, Kernig’s or Brudzinski’s sign

 SALIENTFEATURES
SALIENT FEATURES
• 1-2 bottles of beer per day, up to 3-4 bottles
Subjective:
• 60 year old
• Male
• Diabetes mellitus (DM) type II for 5 year
 Sitagliptin + Metformin 50mg + 1000 mg OD
• Hypertension (HTN) St. II for 3 years
 Amlodipine + Olmesartan 5mg /20mg OD
• 3months PTC, sudden onset of pain (burning-like)
sensation started with right foot first and then
left and worsen especially at night.
• Denies any ROM limitations, weakness, tremors,
twitching, swelling, redness or musculoskeletal
trauma
• Childhood illness: patient claims that he had,
mumps, chicken pox, measles.
• BP monitoring was ranging 130-140/80-90
mmHg.
• Not able to monitor his blood glucose levels for
the past few months.
• Smokes 1 pack per day x 20 years (20 pack years),
during occasions. Objective:
• BMI = 30.14 kg/m2 (Obese II)
• Since retired already, he has less physical
activity, he usually does gardening.
• Patients diet history reveals excessive
• Slight tenderness on upon passive ROM
carbohydrate intake in the form of bread,
rice and pasta.
of the both feet
 His usual lunch/dinner consists of 1-2
cups rice, meat or sometimes 1-2 • No impairment on position sense,
servings of cooked pasta with 1-2 slices
of bread. vibratory sense and pain sensation of UE
 During the day, he often has “a slice or
two” of bread with butter. & LE except on his both feet noted to
• He also eats eight to ten pieces of fresh fruit have an increase pain sensation.
per day every after meals and during
snacks.
• He prefers chicken and fish, but it is usually
• Decreased ankle DTR (1+)
served with a tomato or cream sauce
accompanied by rice or pasta.
• (-) Lesions/rashes
• (+) polydipsia;
• ​(+) polyphagia​;
• (+) polyuria
• (+) Nocturia
DIFFERENTIAL DIAGNOSIS
GOUTY ARTHRITIS
Rule in:
 60 year old Rule out:
 Male
 Diabetes Mellitus Type II & Hypertension St. II
 No swelling, No redness, No heat
 Sudden onset of pain (burning-like) sensation started
with right foot first and then left usually worsen at night.  Usually single joint is affected (like big toe)
 1-2 bottles of beer per day, up to 3-4 bottles during
occasions.
 BMI = 30.14 kg/m2 (Obese II)
 Slight tenderness on upon passive ROM of the both feet ** Can also be ruled out with Laboratory test
 No impairment on position sense, vibratory sense and
pain sensation of UE & LE except on his both feet noted to determine the level of blood uric acid and
to have an increase pain sensation.
presence of uric acid crystals.

-RULE OUT-
Cont… DIFFERENTIAL DIAGNOSIS
THROMBOANGITIS OBLITERANCE (BUERGER’S DISEASE)
Rule in:
Men
Diabetes Mellitus Type II &
Hypertension St. II
Sudden onset of pain (burning-like)
sensation started with right foot first
and then left usually worsen at night.
Smokes 1 pack per day x 20 years (20
pack years),
-RULE OUT-
Rule out:
 More often in <45 y/o
 No numbness, No tingling
 No skin ulcers/gangrene
 No claudication
*** Can also be ruled out using Arteriography (positive
findings will reveal nonatherosclerotic, segmental occlusive
lesions of small & medium-sized vessels with formation of
distinctive small collateral vessels around areas of occlusion
[corkscrew collaterals])
Cont… DIFFERENTIAL DIAGNOSIS
ATYPICAL HERPES ZOSTER (ZOSTER SINE HERPETE)
Rule in:
60 year old
Diabetes Mellitus Type II
Sudden onset of pain (burning-
like) sensation on both feet.
Childhood illness: chicken pox
(-) Lesions/rashes
-RULE OUT-
Rule out:
Usually unilateral pain
 Usually thoracoabdominal affectation
 Commonly seen face, neck, one side of torso or the
eyes.
 No numbness/itchiness
 (-) Hyper sensitivity to touch
*** Can be also ruled out by PCR test (detect VZV DNA
rapidly and sensitively)
Cont… DIFFERENTIAL DIAGNOSIS
ALCOHOLIC NEUROPATHY
Rule in:
60 year old Rule out:
Male No Sensory symptoms (like numbness, allodynia,
Sudden onset of pain (burning-like) sensation started paresthesia, dysesthesias, and loss of vibration or
with right foot first and then left usually worsen at
position sense)
night.
1-2 bottles of beer per day, up to 3-4 bottles during No motor symptoms (like weakness)
occasions.
 No history of gait ataxia and difficulty walking or a
Slight tenderness on upon passive ROM of the both feet
No impairment on position sense, vibratory sense and history of frequent falls
pain sensation of UE & LE except on his both feet noted *** Can also be ruled out with Laboratory test (Liver
to have an increase pain sensation.
Function Test; Screening for DM; Creatinine; and Thiamine,
Decreased ankle DTR (1+)
B12, Folic acid levels)

-CANNOT TOTALY RULE OUT-

 Cont… DIFFERENTIAL DIAGNOSIS
DIABETIC NEUROPATHY
 60 year old  (+) polydipsia;
 Male  ​(+) polyphagia​;
 Diabetes Mellitus Type II & Hypertension St. II
 (+) polyuria
 Sudden onset of pain (burning-like) sensation started
with right foot first and then left foot usually worsen at  (+) Nocturia
-RULE IN-

night.  BMI = 30.14 kg/m2 (Obese II)

 Not able to monitor his blood glucose levels for the past
few months.  Slight tenderness on upon passive ROM of the
both feet
 Smokes 1 pack per day x 20 years (20 pack years)
 No impairment on position sense, vibratory
 1-2 bottles of beer per day, up to 3-4 bottles during
occasions.
sense and pain sensation of UE & LE except on
his both feet noted to have an increase pain
 Since he is retired already, he has less physical activity, sensation.
he usually does gardening.
 Decreased ankle DTR (1+)
 Patients diet history reveals excessive carbohydrate
intake in the form of bread, rice and pasta.
IMPRESSION:

PERIPHERAL NEUROPATY SECONDARY TO TYPE 2 DIABETES MELLITUS r/o ALCOHOLIC NEUROPATHY

DIABETES MELLITUS TYPE 2

HYPERTENSIVE STAGE II – CONTROLLED

HYPERLIPIDEMIA

OBESE II
DISCUSSION
TYPE 2 DIABETES MELLITUS:
COMPLICATIONS
 PREVALENCE
 Number of people with diabetes rose
from 108422 M (19802014)
 Global prevalence of diabetes among
adults over 18y/o rose from 4.7 
8.5% in (1980  2014).
 Between 2000 and 2016, there was a
5% increase in premature mortality
from diabetes.
 Rising more rapidly in low and
middle income countries than in high
income countries.
 Diabetes is a major cause of blindness,
kidney failure, heart attacks, stroke and
lower limb amputation.
 In 2016, an estimated 1.6 million deaths
were directly caused by diabetes. Another
2.2 million deaths were attributable to
high blood glucose in 2012.
 Almost half of all deaths attributable to
high blood glucose occur before the age of
70 years.
 WHO estimates that diabetes was the
seventh leading cause of death in 2016.
IDF Diabetes Atlas Ninth edition 2019 provides the latest
figures, information and projections on diabetes worldwide.

In 2019,
• Approximately 463 million
adults (20-79 years) were living
with diabetes; by 2045 this will rise
to 700 million
• The proportion of people with type
2 diabetes is increasing in most
countries
• 79% of adults with diabetes
were living in low- and middle-
income countries
• 1 in 5 of the people who are above 65
years old have diabetes
• 1 in 2 (232 million) people with
diabetes were undiagnosed
• Diabetes caused 4.2 million deaths
• Diabetes caused at least USD 760
billion dollars in health expenditure in
2019 – 10% of total spending on adults
• 374 million people are at increased
risk of developing type 2 diabetes
PREVALENCE

The Philippines LAST UPDATE: 14/05/2020

The Philippines is one of the 39 countries and territories of the IDF WP region.
463 million people have diabetes World-wide and
163 million people in the WP Region;
by 2045 this will rise to 212 million.
Total adult population : 63,265,700
Prevalence of diabetes in adults : 6.3%
Total cases of diabetes in adults : 3,993,300
• Diabetes-related complications • Type 2 DM often has a long
affect many organ systems asymptomatic period of
• Responsible for the majority of hyperglycemia before diagnosis,
morbidity and mortality many individuals with type 2 DM
• In the United States, diabetes is the have complications at the time of
leading cause of new blindness in diagnosis.
adults, renal failure, and • Can be prevented or delayed:
nontraumatic lower extremity  early detection,
amputation.  aggressive glycemic control,
• Usually do not appear until the  efforts to minimize the risks of
second decade of hyperglycemia. complications.
 Retinopathy
Non-proliferative
Proliferative
EYE DISEASE
Macular edema

SENSORY & MOTOR

MICROVASCULA  Mononeuropathy
R
 Polyneuropathy
NEUROPATHY
AUTONOMIC
NEPHROPATHY
 Albuminuria
VASCULAR  Declining renal function Other comorbid conditions
associated with diabetes
(relationship to
Coronary hyperglycemia is uncertain)
 Depression
OTHERS:
heart disease Gastrointestinal  Obstructive sleep apnea
 Gastroparesis  Fatty liver disease
DM-Related  Diarrhea  Hip fracture
Complications Peripheral  Genitourinary  Cognitive impairment
MACROVASCULAR  Uropathy  Dementia
arterial disease  Sexual Dysfunction  Low testosterone in men
 Dermatologic
 Infectious
NON- Cerebrovascular
 Cataracts
OTHERS disease
 Glaucoma
VASCULAR  Cheiroarthropathy
 Periodontal disease
 Hearing loss
 MICROVASCULAR
 Nephropathy:
Presence of chronic kidney
disease and/or albuminuria
 Retinopathy:
History of retinopathy or retinal
laser photocoagulation
 Neuropathy:
Autonomic neuropathy,
peripheral neuropathy, and
erectile dysfunction

MACROVASCULAR
 Coronary artery disease:
History of coronary artery
disease, angina, myocardial
infarction, percutaneous
coronary intervention, and
coronary artery bypass grafting
 Cerebrovascular disease:
Stroke, transient ischemic
attack, carotid artery stenting,
and carotid endarterectomy
 Peripheral artery disease:
History of peripheral artery
disease including
revascularization procedures,
diabetic foot, and amputation

Source:
DISCOVER study
 GLYCEMIC CONTROL &
COMPLICATIONS
• The microvascular complications of both type 1 and type 2 DM result
from chronic hyperglycemia.
• Evidence implicating a causative role for chronic hyperglycemia in the
development of macrovascular complications is less conclusive.
• CHD events and mortality rate are 2-4x greater in patients with type 2
DM and correlate with fasting and postprandial plasma glucose levels
as well as the hemoglobin A1c (HbA1c).
• Other factors such as dyslipidemia and hypertension also play
important roles in macrovascular complications.
The United Kingdom Prospective
Diabetes Study (UKPDS)
 >5000 individuals with type 2 DM for >10 years.
 This study used multiple treatment regimens and
monitored the effect of intensive glycemic control and risk
factor treatment on the development of diabetic
complications.
 Newly diagnosed individuals with type 2 DM were
randomized with the goal of symptom prevention.
 Intensive management using various combinations of
insulin, sulfonylurea or metformin
 Conventional therapy using dietary modification and
pharmacotherapy
 INTENSIVE TREATMENT arm achieved an HbA1c of 7%,
compared to a 7.9% in the STANDARD TREATMENT group.
 Each percentage point reduction in HbA1c was
associated with a 35% reduction in microvascular
complications.
Improved glycemic control also reduced
the cardiovascular event rate in the
follow-up period of >10 years
Strict BP control significantly reduced
both macrovascular & microvascular
complications.
The beneficial effects of BP control >
glycemic control.
Lowering BP to moderate goals (144/82
mmHg) reduced the risk of DM related
death, stroke, microvascular endpoints,
retinopathy, and heart failure (risk
reductions between 32 and 56%).
 Long-Term Results of the Kumamoto Study on
Optimal Diabetes Control in Type 2 Diabetic Patients

• Similar reductions in the risks of retinopathy and nephropathy

were also seen in a small trial of lean Japanese individuals with
type 2 DM
• Randomized to either intensive glycemic control or standard
therapy with insulin.
• Results demonstrate the effectiveness of intensive glycemic
control can delay the onset and progression of the early stages of
diabetic microvascular complications
• The ACCORD (Action to Control Cardiovascular Risk in Diabetes) and
ADVANCE (Action in Diabetes and Vascular Disease: Preterax and
Diamicron MR Controlled Evaluation) trials also found that improved
glycemic control reduced microvascular complications.

• Chronic hyperglycemia plays a causative role in the pathogenesis of

diabetic microvascular complications.
• Cardiovascular events were reduced at follow-up of >10 years, even
though the improved glycemic control was not maintained.
• The positive impact of a period of improved glycemic control on
later disease has been termed a legacy effect or metabolic memory.
 FEATURES OF DIABETES-RELATED
COMPLICATIONS
1) Duration/degree of hyperglycemia
correlate with complications.
2) Intensive glycemic control is
beneficial in all forms of DM.
3) Blood pressure control is critical,
especially in type 2 DM.
4) Survival in patients with type 1 DM
is improving, and diabetes-related
complications are declining.
5) Not all individuals with diabetes
develop diabetes-related
complications. Other incompletely
defined factors appear to modulate the
development of complications.
** Many of these patients have glycemic
control that is indistinguishable from those
who develop microvascular complications,
suggesting a genetic susceptibility for
developing particular complications.
MECHANISMS OF COMPLICATIONS
• Chronic hyperglycemia is an important etiologic factor leading to
complications of DM
• The mechanism(s) by which it leads to such diverse cellular and organ
dysfunction is unknown.
• An emerging hypothesis is that hyperglycemia leads to epigenetic
changes that influence gene expression in affected cells.
 Increased
MECHANISMS intracellular glucose
OF
COMPLICATIONS
Advance glycosylation
end products

Nonenzymatic glycosylation of
intra- & extra- cellular proteins

Bind to the cell

surface receptor

Cross-linking of Accelerated Glomerular Endothelial Altered extracellular

proteins atherosclerosis dysfunction dysfunction matrix composition
MECHANISMS OF
COMPLICATIONS
Hyperglycemia

Using aldose reductase

Sorbitol Pathway
inhibitors, has not
(aldose reductase)
demonstrated beneficial effects

Increases
glucose
metabolism
 Hyperglycemia

MECHANISMS OF
Increases the
COMPLICATIONS formation of
diacylglycerol

Activation of
protein kinase C

Alters the
transcription of
genes

Contractile Extracellular
Fibronectin Type IV collagen
proteins matrix proteins

Endothelial cells Neurons

 Hyperglycemia
MECHANISMS OF
COMPLICATIONS
Hexosamine Fructose-6-phosphate
pathway

O-linked glycosylation Proteoglycan production

Changes in gene expression of

Altered function by transforming growth factor β
Plasminogen
glycosylation of proteins (TGF-β) activator inhibitor-1

Endothelial nitric
oxide synthase
MECHANISMS OF COMPLICATIONS
• Growth factors may play an important role in some diabetes-related
complications, and their production is increased by most of these
proposed pathways.
• Vascular endothelial growth factor A (VEGF-A) is increased locally in
diabetic proliferative retinopathy.
• TGF-β is increased in diabetic nephropathy and stimulates basement
membrane production of collagen and fibronectin by mesangial cells.
• The possible unifying mechanism is that hyperglycemia leads to
increased production of reactive oxygen species or superoxide in the
mitochondria; these compounds may activate all four of the pathways
NEUROPATHY AND DIABETES MELLITUS
• Diabetic neuropathy occurs in ~50%
of individuals with long standing type
1 & type 2 DM.
• It may manifest as
 Polyneuropathy,
 Mononeuropathy
 Autonomic neuropathy.
• As with other complications of DM,
the development of neuropathy
correlates with:
 Duration of diabetes
 Glycemic control
• Other risk factors:
 BMI, (the greater the BMI, the greater the risk
of neuropathy)
 Smoking.
 Presence of CVD
 Elevated triglycerides
 Hypertension
• Both myelinated and unmyelinated nerve
fibers are lost.
• Clinical features of are similar to those of
other neuropathies, the diagnosis of
diabetic neuropathy should be made only
after the other possible etiologies are
excluded
POLYNEUROPATHY
• The most common form of diabetic • Pain typically involves the lower
neuropathy is distal symmetric extremities, is usually present at rest, and
polyneuropathy. worsens at night.
• It most frequently presents with distal sensory • The acute form is sometimes treatment-
loss and pain, but up to 50% of patients do not related, occurring in the context of
have symptoms of neuropathy. improved glycemic control.
• Any combination of these symptoms may
• As diabetic neuropathy progresses, the pain
develop as neuropathy progresses:
 Hyperesthesia
subsides and disappears, but a sensory
 Paresthesia deficit in the lower extremities persists.
 Dysesthesia • PE:
 Sensation of numbness, tingling, sharpness, or  Sensory loss,
burning that begins in the feet and spreads  Loss of ankle deep-tendon reflexes
proximally.
 Abnormal position sense
 Neuropathic pain.
 DIABETIC POLYRADICULOPATHY
• Syndrome characterized by severe disabling pain in the distribution of
one or more nerve roots.
• It may be accompanied by motor weakness.
• Intercostal/truncal radiculopathy  pain over the thorax/abdomen.
• Involvement of the lumbar plexus / femoral nerve  severe pain in
the thigh/hip and may be associated with muscle weakness in the
hip flexors or extensors (diabetic amyotrophy).
• Usually self-limited and resolve over 6–12 months.
MONONEUROPATHY
• Mononeuropathy (dysfunction of
isolated cranial or peripheral
nerves) is less common than
polyneuropathy and presents with
pain and motor weakness in the
distribution of a single nerve.
• Occur at entrapment sites (carpal
tunnel) or non-compressive
(vascular etiology).
• Third cranial nerve is most
common  diplopia.
• PE:
 Ptosis
 Ophthalmoplegia
 Normal pupillary constriction to light
• Sometimes other cranial nerves,
such as IV, VI, or VII (Bell’s palsy),
are affected.
• Peripheral mononeuropathies or
simultaneous involvement of more
than one nerve (mononeuropathy
multiplex) may also occur.
Autonomic Neuropathy
• Individuals with long-standing type 1 or 2 DM may Reduce
develop signs of autonomic dysfunction involving: counterregulatory
 Cholinergic, hormone release
(catecholamines)
 Noradrenergic
 Peptidergic (peptides such as pancreatic polypeptide,
substance P, etc.)
• Can involve multiple systems: Inability to sense
Cardiovascular  Resting tachycardia and orthostatic hypoglycemia
hypotension appropriately
(hypoglycemia unawareness)
Gastrointestinal  Gastroparesis
Genitourinary  Bladder emptying abnormalities
Sudomotor:
® Hyperhidrosis of the upper extremities
® Anhidrosis of the lower extremities Complicating efforts
Risk of severe
 Anhidrosis of the feet can promote dry skin with cracking, which to improve glycemic
increases the risk of foot ulcers. hypoglycemia
control
Metabolic systems
• Improved glycemic control should be
aggressively pursued
® Improve nerve conduction velocity
® Symptoms of diabetic neuropathy may not
necessarily improve.
• Efforts to improve glycemic control in long-
standing diabetes may be confounded by
autonomic neuropathy and hypoglycemia
unawareness.
• Risk factors like hypertension and
hypertriglyceridemia should be treated.
• Avoidance of neurotoxins (alcohol) and smoking,
• Supplementation with vitamins for possible
deficiencies (B12, folate),
• Symptomatic treatment are the
mainstays of therapy.
• Loss of sensation in the foot 
risk for ulceration and its
sequelae.
 Prevention of such problems
Check their feet daily
 Take precautions (footwear) 
preventing calluses or ulcerations.
• If foot deformities  Podiatrist
• Chronic, painful diabetic neuropathy
is difficult to treat but may respond to:
Duloxetine  Amitriptyline
 Gabapentin  Valproate
 Pregabalin  Opioids
• Duloxetine and Pregabalin, approved
by the U.S. FDA for pain associated
with diabetic neuropathy, but no
treatments are satisfactory.
• Referral to a pain management center
may be necessary.
• Pain of acute diabetic
neuropathy may resolve over
time.
• Medications may be
discontinued as progressive
neuronal damage from DM
occurs.
• Therapy of orthostatic • Nonpharmacologic maneuvers
hypotension secondary to  Adequate salt intake
autonomic neuropathy is also  Avoidance of dehydration and
challenging. diuretics
• A variety of agents have limited  Lower extremity support hose
success:
 Fludrocortisone
 Midodrine
 Clonidine
 Octreotide
 Yohimbine
 STEPS TO PREVENT OR DELAY NERVE
DAMAGE
Keep your blood sugar levels in your target range
• Meal planning, physical activity and medications, if needed, all can
help you reach your target range.
• There are two ways to keep track of your blood sugar levels:
 Use a blood glucose meter to
 Help you make decisions about day-to-day care.
 Get an A1C test (a lab test) at least twice a year
 To find out your average blood sugar for the past 2-3 months.
• Checking your blood sugar levels will tell you whether your diabetes
care plan is working or whether changes are needed.
Treatment:
 Intensive glycemic and blood pressure control
 During the first 6–12 mos. of improved glycemic control, established diabetic MILD
retinopathy may transiently worsen (temporary)
 Prophylactic laser photocoagulation when initiating intensive therapy.
Non-proliferative  May progress to more
extensive disease
 Advanced retinopathy is present  glycemic control (less benefit). Late in the first decade or early in
 Changes in venous vessel
the second decade of the disease.
 Regular, comprehensive eye examinations & adequate ophthalmologic care can prevent caliber
 retinal vascular
most blindness.  Intraretinal microvascular
 Microaneurysms
 Laser photocoagulation is very successful in preserving vision. abnormalities
 Blot hemorrhages
 Proliferative retinopathy is usually treated with panretinal laser photocoagulation  Numerous microaneurysms
 Cotton-wool spots and hemorrhages.
 Macular edema is treated with focal laser photocoagulation and anti–vascular
 Pathophysiologic Mechanism:
endothelial growth factor therapy (ocular injection).
Loss of retinal pericytes,
 Aspirin therapy does not appear to influence the natural history of diabetic retinopathy.
Inc. retinal vascular permeability
Alterations in retinal blood flow SEVERE
Abnormal retinal microvasculature,
 Greater the chance of evolution
 Retinal ischemia.
to proliferative retinopathy within 5
Retinopathy years.

OPHTHALMOLOGIC
COMPLICATIONS OF Proliferative
DIABETES MELLITUS
Macular edema  Hallmark: neovascularization
DM is the leading cause of in response to retinal hypoxemia.
blindness ages of 20 – 74 in Fluorescein  Pathophysiologic Mechanism:
the United States. angiography and optical Newly formed vessels appear
25x more likely to be coherence tomography (optic nerve and/or macula)
legally blind  Rupture easily
25% chance of
 Vitreous hemorrhage
moderate visual loss over
 Fibrosis
the next 3 years.
 Retinal detachment .
 RENAL COMPLICATIONS OF DIABETES
MELLITUS
• Diabetic Nephropathy is the leading cause of chronic kidney
disease (CKD), ESRD, and CKD requiring renal replacement
therapy.
• Prognosis of diabetic patients on dialysis is poor, w/ survival
• Albuminuria in individuals with DM is associated with an
increased risk of cardiovascular disease.
• Individuals with diabetic nephropathy commonly have diabetic
retinopathy.
• Pathogenesis: related to chronic hyperglycemia, although
incompletely defined, involve the effects of:
 Soluble factors (growth factors, angiotensin II, endothelin,
advanced glycation end products [AGEs]),
 Hemodynamic alterations in the renal microcirculation
(glomerular hyperfiltration or hyperperfusion, increased
glomerular capillary pressure)
 Structural changes in the glomerulus (increased extracellular
matrix, basement membrane thickening, mesangial expansion,
fibrosis).
• Smoking accelerates the decline in renal function.
• 20–40% of patients with diabetes develop
diabetic nephropathy
• Known risk factors:
Race (African-Americans, Native Americans,
and Hispanic )
Family history
• First years after the onset of DM, glomerular
hyperperfusion and renal hypertrophy are
associated with an increase of the GFR.
• First 5 years of DM, thickening of the glomerular
basement membrane, glomerular hypertrophy,
and mesangial volume expansion occur as the GFR
returns to normal.
 RENAL COMPLICATIONS OF DIABETES
MELLITUS
American Diabetes Association (ADA)
• Increased urinary protein
 Microalbuminuria
30–299 mg/d in a 24-h collection
30–299μg/mg creatinine in a spot
collection
“persistent albuminuria (30–299 mg/
24h)”
 Macroalbuminuria
>300 mg/24 h
“persistent albuminuria (≥300 mg/24 h)”
*** To better reflect the continuous nature of
albumin excretion in the urine as risk factor for
nephropathy and cardiovascular disease (CVD).
• Microalbuminuria or macroalbuminuria may be
present when type 2 DM is diagnosed (long
asymptomatic period)
• Hypertension more commonly accompanies
microalbuminuria or macroalbuminuria
• Microalbuminuria may be less predictive of
diabetic nephropathy and likelihood of progression
to macroalbuminuria in type 2 DM, in large part
due to increased CV mortality in this population.
• Albuminuria may be secondary to factors
unrelated to DM:
Hypertension
congestive heart failure (CHF)
Prostate disease
Infection.
TREATMENT: Diabetic Nephropathy
• Albuminuria should be detected at an early
stage when effective therapies can be
instituted.
• GFR in the absence of albuminuria, annual
measurement of the serum creatinine to
estimate GFR should also be performed.
• Annual microalbuminuria measurement
(albumin-to-creatinine ratio in spot urine)
• Routine urinalysis does not detect these
low levels of albumin excretion.
• Screening for albuminuria should
commence at the time of diagnosis.
• Type IV renal tubular acidosis (hyporeninemic
hypoaldosteronism)
• These individuals develop a propensity to hyperkalemia
and acidemia, which may be exacerbated by medications
(ACE inhibitors, ARBs, and spironolactone).
• Patients with DM are predisposed to radiocontrast-
induced nephrotoxicity.
• Risk factors for radiocontrast-induced nephrotoxicity:
 Preexisting nephropathy
 Volume depletion.
• Individuals with DM undergoing radiographic procedures
with contrast dye should be:
 Well hydrated before and after dye exposure, and the
serum creatinine
 Monitored for 24–48 h following the procedure.
• Metformin should be held if indicated.
TREATMENT: Diabetic Nephropathy
• Optimal therapy for diabetic
nephropathy is prevention by
control of glycemia.
• Interventions effective in slowing
progression of albuminuria:
Improved glycemic control
Strict BP control
Administration of an ACE
inhibitor or ARBs.
• Dyslipidemia should also be treated
• Improved glycemic control reduces the rate at which
microalbuminuria appears and progresses.
• Once macroalbuminuria is present, it is unclear whether
improved glycemic control will slow progression of renal
disease.
• If ACE inhibitors or ARBs is not possible or the BP is not
controlled, then, diuretics, calcium channel blockers
(non-dihydropyridine class), or beta blockers should be
used.
• Complications of atherosclerosis are the leading cause
of death in DM nephropathy and hyperlipidemia should
be treated aggressively.
• Renal transplantation from a living related donor is the
preferred therapy, requires chronic immunosuppression.
• Combined pancreas-kidney transplant offers the
promise of normoglycemia and freedom from dialysis.
 GASTROINTESTINAL GENITOURINARY
DYSFUNCTION DYSFUNCTION
• The most prominent GI symptoms: • Diabetic autonomic neuropathy may lead to
 Delayed gastric emptying (gastroparesis) genitourinary dysfunction:
 Altered small- and large-bowel motility (constipation or diarrhea). Cystopathy
• Gastroparesis may present with symptoms: Female sexual dysfunction (reduced sexual desire, dyspareunia,
 Anorexia reduced vaginal lubrication). Symptoms of
 Nausea/Vomiting • Cystopathy
 Early satiety,
Inability to sense a full bladder and a failure to void completely.
 Abdominal bloating.
As bladder contractility worsens, bladder capacity and the
• Retinopathy and neuropathy are usually present. postvoid residual increase  s/sx:
Urinary hesitancy,
• Nuclear medicine scintigraphy  document delayed gastric emptying, but
may not correlate well with the patient’s symptoms. Decreased voiding frequency
Incontinence
• Noninvasive “breath tests”  have been developed, but are not yet Recurrent urinary tract infections.
validated.
Diagnostic evaluation:
• Parasympathetic dysfunction secondary to chronic hyperglycemia is Cystometry
important in the development of gastroparesis, hyperglycemia itself also Urodynamic studies.
impairs gastric emptying.
• Erectile dysfunction and retrograde ejaculation are very
• Nocturnal diarrhea, alternating with constipation, is a feature of DM-
related GI autonomic neuropathy.
common in DM and may be one of the earliest signs of
diabetic neuropathy
TREATMENT:
Gastrointestinal Dysfunction
• Improved glycemic control should be a primary
goal, because some aspects (neuropathy 
gastric function) may improve.
• Smaller, more frequent meals that are easier to
digest (liquid) and low in fat and fiber may
minimize symptoms of gastroparesis.
• Metoclopramide has been used but is now
restricted in both the United States and Europe.
Not advised for long-term use.
• Gastric electrical stimulatory devices are
available but not approved.
• Diabetic diarrhea in the absence of bacterial
overgrowth is treated symptomatically
TREATMENT:
Genitourinary Dysfunction
• Diabetic cystopathy should be treated
with scheduled voiding or self-
catheterization.
• Drugs that inhibit type 5-
phosphodiesterase are effective for
erectile dysfunction, but their efficacy
in individuals with DM is slightly lower
• Sexual dysfunction in women may be
improved with use:
Vaginal lubricants
Treatment of vaginal infections
Systemic or local estrogen replacement
 CARDIOVASCULAR MORBIDITY AND
MORTALITY
• CVD is increased • The AHA has designated DM as a “CHD risk equivalent,”
and type 2 DM patients without a prior MI have a similar
• FH Study  marked increase (one- to fivefold) in DM
risk for coronary artery–related events as nondiabetic
 PAD individuals who have had a prior MI.
 Coronary artery disease
• Cardiovascular risk is lower and not equivalent in a
 MI younger individual with a brief duration of type 2 DM.
 CHF
• Extremely high prevalence of underlying CVD in individuals
• Prognosis for individuals with diabetes who have coronary with diabetes, evidence of atherosclerotic vascular disease
artery disease or MI is worse than for nondiabetics. should be sought who has symptoms suggestive of cardiac
• CHD is more likely to involve multiple vessels in individuals
ischemia or peripheral or carotid arterial disease.
with DM. • The screening of asymptomatic individuals with diabetes
• Cerebrovascular disease is increased in individuals with DM for CHD, even with a risk-factor scale, is not recommended
(threefold increase in stroke).  recent studies have not shown a clinical benefit.
• Type 2 DM increases the cardiovascular death rate: • The absence of chest pain (“silent ischemia”) is common in
individuals with diabetes, and a thorough cardiac
 Two-fold in men evaluation should be considered prior to major surgical
 Four-fold in women. procedures.
 CARDIOVASCULAR MORBIDITY AND
MORTALITY
• Increase in cardiovascular morbidity and • Additional risk factors more prevalent in the
mortality rates in diabetes appears to relate diabetic population:
to the synergism of hyperglycemia with other  Microalbuminuria
cardiovascular risk factors.  Macroalbuminuria
• Risk factors for macrovascular disease in  Elevation of serum creatinine
diabetic individuals:  Abnormal platelet function
 Dyslipidemia
 Endothelial dysfunction
 Hypertension
• Treatment with insulin and the sulfonylureas
 Obesity
did not increase the risk of CVD in type 2 DM.
 Reduced physical activity
 Cigarette smoking.
TREATMENT: Cardiovascular Disease
• Revascularization procedures for CHD
 Percutaneous coronary interventions (PCI)
 Coronary artery bypass grafting (CABG)
• Diabetic patients have higher rates of restenosis and
lower long-term patency and survival rates.
• Aggressive cardiovascular risk modification in all
individuals with DM and glycemic control should be
individualized
• CHD and type 2 DM:
 ACE inhibitor (or ARB),
 Statin
 Acetylsalicylic acid (ASA; aspirin)
• Using beta blockers in individuals who have diabetes
should not prevent use  benefit diabetic patients after
MI.
• CHF  thiazolidinediones should not be used
• Metformin can be used in patients with stable CHF, if
the renal function is normal.
• Antiplatelet therapy reduces cardiovascular events in
individuals with DM who have CHD and is
recommended.
• ADA: include the use of aspirin for primary prevention
of coronary events in diabetic individuals with an
increased 10-year cardiovascular risk >10% (at least
one risk factor)
Hypertension
Smoking
Family history
Albuminuria
Dyslipidemia: MEN >50 y/o or WOMEN >60 y/o
• ASA is not recommended for primary prevention in
those with a 10-year cardiovascular risk <10%.
CARDIOVASCULAR RISK FACTORS: Dyslipidemia
• The most common pattern of dyslipidemia
 Hypertriglyceridemia
 Reduced high-density lipoprotein
(HDL) cholesterol levels.
• DM itself does not increase levels of low-
density lipoprotein (LDL)
• Small dense LDL particles found in type 2
DM are more atherogenic because they are
more easily glycated and susceptible to
oxidation.
• Reductions in LDL reduce cardiovascular
events and morbidity in individuals with
DM.
• ADA: Priorities in the treatment of dyslipidemia
are as follows:
lower the LDL cholesterol
raise the HDL cholesterol
decrease the triglycerides.
• Treatment strategy depends on the pattern of
lipoprotein abnormalities.
• Initial therapy for all forms of dyslipidemia, include:
Dietary changes
Lifestyle modifications (smoking cessation, BP control,
weight loss, increased physical activity).
• The dietary recommendations include:
Increased monounsaturated
Fat
Carbohydrates
Reduced saturated fats and cholesterol
CARDIOVASCULAR RISK FACTORS: Dyslipidemia
• Target lipid values in diabetic individuals (age • Improvement in glycemic
>40 years) without CVD should be as follows:
 LDL <2.6 mmol/L (100 mg/dL) control will lower triglycerides
 HDL >1 mmol/L (40 mg/dL) in men & >13 mmol/L and have a modest beneficial
(50 mg/dL) in women
 Triglycerides <1.7 mmol/L (150 mg/dL).
effect by raising HDL.
• ADA: In patients >40 years, recommends • If the patient is known to have
addition of a statin, regardless of the LDL CHD, ADA recommends: LDL
level, in patients with CHD and those
without CHD who have CHD risk factors. goal of <18 mmol/L (70 mg/dL)
• ACC/AHA: recommend that diabetic
individuals aged 40–75 without CHD and a
LDL of 70–189 mg/dl receive “moderate”
intensity statin therapy.
CARDIOVASCULAR RISK FACTORS: Dyslipidemia
• The ACC/AHA: do not advocate a
specific LDL for statin therapy.
• HMG-CoA reductase inhibitors are
the agents of choice for lowering LDL.
• Combination therapy with an HMG-
CoA reductase inhibitor and a fibrate
or another lipid-lowering agent
(ezetimibe, niacin) may be considered
but increases the possibility of side
effects such as myositis and has not
been shown to be beneficial.
• Nicotinic acid effectively raises HDL and
can be used in patients with diabetes, but
may worsen glycemic control and increase
insulin resistance and has not been shown
to provide additional benefit
• Bile acid–binding resins should not be
used if hypertriglyceridemia is present.
• In large clinical trials, statin usage is
associated with a mild increase in the risk
of developing type 2 DM.
• The cardiovascular benefits of statin use
outweigh the mildly increased risk of
diabetes.
 CARDIOVASCULAR RISK FACTORS: Hypertension
• Accelerate other complications of DM, • Realizing that more than one agent is usually required
particularly CVD, nephropathy, and retinopathy. to reach the blood pressure goal, the ADA
recommends that all patients with diabetes and
• Target goal of BP: <140/80 mmHg, but should hypertension be treated with an ACE inhibitor or an
be individualized ARB.
• Therapy should first emphasize lifestyle • Subsequently, agents that reduce cardiovascular risk
(beta blockers, thiazide diuretics, and calcium channel
modifications such as: blockers) should be incorporated into the regimen.
 Weight loss • ACE inhibitors and ARBs are likely equivalent in most
 Exercise patients with diabetes and renal disease.
 Stress management • Serum potassium and renal function should be
monitored.
 Sodium restriction
• High prevalence of atherosclerotic disease in
• In some younger individuals, the provider may individuals with type 2 DM, the possibility of
target a BP of <130/80 mmHg. renovascular hypertension should be considered when
the blood pressure is not readily controlled
LOWER EXTREMITY COMPLICATIONS
• DM is the leading cause of nontraumatic lower
extremity amputation in the United States.
• Foot ulcers and infections are also a major source
of morbidity in individuals with DM.
• The reasons for the increased incidence of these
disorders in DM involve the interaction of several
pathogenic factors:
 Neuropathy
 Abnormal foot biomechanics
 PAD
 Poor wound healing
• The peripheral sensory neuropathy interferes with
normal protective mechanisms and allows the
patient to sustain major or repeated minor trauma
to the foot, often without knowledge of the injury.
• Disordered proprioception causes abnormal
weight bearing while walking and subsequent
formation of callus or ulceration.
• Motor and sensory neuropathy lead to abnormal
foot muscle mechanics and to structural changes in
the foot
 Hammer toe
 Claw toe deformity
 Prominent metatarsal heads
 Charcot joint
• Autonomic neuropathy results in anhidrosis and
altered superficial blood flow in the foot, which
promote drying of the skin and fissure formation.
• PAD and poor wound healing impede resolution of
minor breaks in the skin, allowing them to enlarge
and to become infected.
 LOWER EXTREMITY TREATMENT:
Lower Extremity
COMPLICATIONS Complications
• Many individuals with type 2 DM develop a foot ulcer • Prevention through identification of high-
and a significant subset who develop an ulceration will
ultimately undergo amputation (14–24% risk with that
risk patients, education of the patient, and
ulcer or subsequent ulceration). institution of measures to prevent
• Risk factors for foot ulcers or amputation include:
ulceration.
 Male sex • High-risk patients should be identified during
 Diabetes for >10 years the routine, annual foot examination
 Peripheral neuropathy performed on all patients with DM.
 Abnormal structure of foot (bony abnormalities, callus,
thickened nails) • If the monofilament test or one of the other
 PAD tests is abnormal, the patient is diagnosed
 Smoking with loss of protective sensation  screening
 History of previous ulcer or amputation, for asymptomatic PAD in individuals >50
 Visual impairment years of age who have diabetes and other
 Poor glycemic control. risk factors using ankle brachial index testing
• Large calluses are often precursors to or overlie in high-risk individuals.
ulcerations
TREATMENT:
Lower Extremity Complications
• Patient education should emphasize • Attention to other risk factors for vascular disease (smoking,
 Careful selection of footwear dyslipidemia, hypertension) and improved glycemic control.
 Daily inspection of the feet to detect early signs of poor-fitting • Despite preventive measures, foot ulceration and infection are
footwear or minor trauma common and represent a serious problem.
 Daily foot hygiene to keep the skin clean and moist • Multifactorial pathogenesis of lower extremity ulcers,
 Avoidance of self-treatment of foot abnormalities and high-risk management of these lesions is multidisciplinary and often
behavior (walking barefoot) demands expertise in
 Prompt consultation with a health care provider if an  Orthopedics
abnormality arises.  Vascular surgery
• Patients at high risk for ulceration or amputation may benefit from  Endocrinology
evaluation by a foot care specialist.  Podiatry
 Infectious diseases
• Calluses and nail deformities should be treated by a podiatrist.
• The plantar surface of the foot is the most common site of
• Interventions directed at risk factor modification: ulceration.
 Orthotic shoes and devices • Ulcers may be primarily neuropathic (no accompanying
 Callus management infection) or may have surrounding cellulitis or osteomyelitis.
 Nail care • Cellulitis without ulceration is also frequent and should be
 Prophylactic measures to reduce increased skin pressure from treated with antibiotics that provide broad-spectrum
abnormal bony architecture. coverage, including anaerobes
TREATMENT:
Lower Extremity Complications
• Patient education should emphasize • An infected ulcer is a clinical diagnosis, because superficial culture
 Careful selection of footwear of any ulceration will likely find multiple possible bacterial species.
 Daily inspection of the feet to detect early signs of poor-fitting • The infection surrounding the foot ulcer is often the result of
footwear or minor trauma multiple organisms, with aerobic gram-positive cocci (staphylococci
 Daily foot hygiene to keep the skin clean and moist including MRSA, Group A and B streptococci) being most common
and with aerobic gram-negative bacilli and/or obligate anaerobes as
 Avoidance of self-treatment of foot abnormalities and high-risk co-pathogens.
behavior (walking barefoot)
• Gas gangrene may develop in the absence of clostridial infection.
 Prompt consultation with a health care provider if an
abnormality arises. • Cultures taken from the surface of the ulcer are not helpful; a
culture from the debrided ulcer base or from purulent drainage or
• Patients at high risk for ulceration or amputation may benefit from aspiration of the wound is the most helpful.
evaluation by a foot care specialist.
• Wound depth should be determined by inspection and probing with
• Calluses and nail deformities should be treated by a podiatrist. a blunt-tipped sterile instrument.
• • Plain radiographs of the foot should be performed to assess the
Interventions directed at risk factor modification:
possibility of osteomyelitis in chronic ulcers that have not responded
 Orthotic shoes and devices to therapy.
 Callus management • Magnetic resonance imaging (MRI) is the most specific modality,
 Nail care with nuclear medicine scans and labeled white cell studies as
 Prophylactic measures to reduce increased skin pressure from alternatives.
abnormal bony architecture. • Surgical debridement is often necessary.
TREATMENT:
Lower Extremity Complications
• Osteomyelitis is best treated by a combination of
prolonged antibiotics (IV, then oral) and/or possibly
debridement of infected bone.
• The possible contribution of vascular insufficiency
should be considered in all patients.
• Peripheral arterial bypass procedures are often effective
in promoting wound healing and in decreasing the need
for amputation of the ischemic limb.
• ADA identified six interventions with demonstrated
efficacy in diabetic foot wounds:
 Off-loading
 Debridement
 Wound dressings
 Appropriate use of antibiotics,
 Revascularization
 Limited amputation
• Oral antibiotics directed predominantly at methicillin-susceptible
staphylococci and streptococci (e.g., dicloxacillin, cephalosporin,
amoxicillin/clavulanate).
• MRSA often requires the use of clindamycin, doxycycline, or
trimethoprim-sulfamethoxazole.
• Trimethoprim-sulfamethoxazole exhibits less reliable coverage of
streptococci than the β-lactams, and diabetic patients may develop
adverse effects including acute kidney injury and hyperkalemia.
• IV antibiotics should provide broad-spectrum coverage directed
toward Staphylococcus aureus, including MRSA, streptococci, gram-
negative aerobes, and anaerobic bacteria.
• Initial antimicrobial regimens include vancomycin plus a β-lactam/β-
lactamase inhibitor or carbapenem or vancomycin plus a combination
of quinolone plus metronidazole.
• Daptomycin, ceftaroline, or linezolid may be substituted for
vancomycin.
• If the infection surrounding the ulcer is not improving with IV
antibiotics, reassessment of antibiotic coverage and reconsideration
of the need for surgical debridement or revascularization are
indicated.
End…