DEFINITION

— The term diabetes mellitus describes a metabolic disorder of multiple etiology

characterized by chronic hyperglycemia with disturbances of carbohydrate, fat, and
protein metabolism resulting from defects in insulin secretion (in both types of DM),
Diabetes Mellitus insulin action, or both.

Dr. Dina Qa’adan

2022

Epidemiology
— Diabetes likely will continue to be one of the most common diagnoses made by family physicians.
— approximately one-fourth of Americans with diabetes are undiagnosed.
— The prevalence of diabetes diagnoses is projected to increase from 9.1% of the U.S. population in 2014 to
13% in 2030 and 17% in 2060.
— Approximately 90% to 95% of people with diabetes have type 2 diabetes.
— Diabetes is an expensive disease, and medical costs for a person with diabetes are double that of a person
without diabetes.
— In 2015, diabetes mellitus was the seventh leading cause of death in the United States.

According to IDF ( International Diabetes Federation) :

— The global diabetes prevalence in 2019 is estimated to be 9.3% (463 million people),
— Rising to 10.2% (578 million) by 2030 and 10.9% (700 million) by 2045.

— The prevalence of D.M in Jordan is 17.1%

 Type Of Diabetes
Secondary Diabetes Mellitus
— Type 1 Diabetes Mellitus: 5-10%, due to β-cell destruction, usually leading to absolute insulin
deficiency, autoimmune and idiopathic forms. The most common causes of secondary diabetes are as follows:
— Type 2 Diabetes Mellitus: 90%, due to a progressive insulin secretory defect on the background of — Diseases of the pancreas that destroy the pancreatic beta cells
insulin resistance.
◦ (eg, hemochromatosis, pancreatitis, cystic fibrosis, pancreatic cancer)
— Gestational Diabetes: any degree of glucose intolerance with onset or first recognition during
— Hormonal syndromes that interfere with insulin secretion
pregnancy.
◦ (eg, Pheochromocytoma)
— Other types:
— Hormonal syndromes that cause peripheral insulin resistance
vLADA (Latent Autoimmune Diabetes of Adulthood) Type 1.5 diabetes: a form of type 1
diabetes with an insidious-slow onset that occurs in middle-aged adults (patients are above 30 ◦ (eg, Acromegaly, Cushing syndrome, Pheochromocytoma)
at time of diagnosis, mostly not obese), presents like type 2 diabetes. Defined by the presence — Drugs
of any β-cell antibody. ◦ (eg, phenytoin, estrogens, Steroids, thiazides, Beta Blocker)
LADA ‫ وﺑﺑﻠش ﻋﻼج ﻋﻠﻰ ھﺎﻷﺳﺎس ﻟﻛن ﺑﻌد ﻓﺗرة ﺑﯾﻔﺷل اﻟﻌﻼج وﺑﺻﯾروا ﯾﺷﻛوا اﻧﮫ‬2‫ﻟﻣﺎ ﯾﯾﺟﻲ ﺑﺎﻟﻌﯾﺎدة ﺑﻔﻛروه ﺗﺎﯾب‬v ◦ ‫ﻣﺟرد ﻣﺎ وﻗﻔﻧﺎ اﻟدواء ﺑطﯾب‬
vMODY (maturity-onset diabetes of youth): 0.5-1%, a type of genetic defects of β-cell function,
present at a young age and have mild disease.
vSecondary Diabetes Mellitus (caused by other illnesses or medications).

Differences between type 1 and type 2 diabetes Diabetes Diagnosis

— Type 1 diabetes is caused by autoimmune destruction of the islet cells of the pancreas, — Diagnostic testing should be performed in individuals with a clinical history indicative of
and onset is typically in childhood. Type 2 diabetes is caused by insulin resistance and is diabetes.
more common in patients who are obese. — Symptoms that should prompt consideration of diabetes include:
◦ polyuria, polydipsia, fatigue, blurry vision, weight loss, poor wound healing, numbness, and tingling.
— Diagnosis of type 2 diabetes can be made using:
— Previously thought to primarily affect adults, type 2 diabetes is now being diagnosed ◦ Fasting plasma glucose
more often in children and adolescents with obesity. ◦ A1C testing
◦ Random plasma glucose testing
◦ Oral glucose tolerance test (OGTT):
— End-organ damage and complications are similar in both types of diabetes. – DO NOT eat or drink anything (other than sips of water) for 8 to 14 hours before your test. (You also cannot eat during
the test).
– You will be asked to drink a liquid that contains glucose (75 g).
– You will have blood drawn before you drink the liquid, and again 2 more times every 60 minutes after you drink it. Each
time, your blood glucose level will be checked.
– Allow at least 2 hours for this test.
 Criteria for Diabetes Diagnosis:
A1C ≥6.5% *

FPG ≥126 mg/dL (7.0 mmol/L) *

Fasting defined as no caloric intake for ≥8 hrs
2-hr PG ≥200 mg/dL (11.1 mmol/L) during OGTT (75-g) *
Performed as described by the WHO, using glucose load containing the equlivalent of 75g anhydrous glucose
dissolved in water
Random PG ≥200 mg/dL (11.1 mmol/L)
In persons with symptoms of hyperglycemia or hyperglycemic crisis

* In the absence of unequivocal hyperglycemia results should be confirmed using repeat testing

Ø Results should be confirmed with repeat testing on a subsequent day; however, a single random
plasma glucose level of 200 mg per dL or greater with typical signs and symptoms of
We need two positive readings of FPG, OGTT, or HbA1C to diagnose DM /or hyperglycemia likely indicates diabetes.
One positive reading of random glucose with hyperglycemia symptoms or crisis Ø Additional testing to determine the etiology of diabetes is not routinely recommended.
.‫ﻌﻤﻞ ﻓﺤﺺ ﺛﺎﻟﺚ ﻣﻦ ﻧﻮع آﺧﺮ‬L ‫ﻴﺠﺔ ﻣﺨﺘﻠﻔﺔ‬H‫ ﻟﻮ ﻃﻠﻌﺖ اﻟﻨ‬,‫ﻢ ﻳﻔﻀﻞ ﻳﻜﻮﻧﻮا ﺑﻴﻮﻣ'ن ﻣﺘﺘﺎﻟﻴ'ن وﻣﻦ ﻧﻔﺲ اﻟﻨﻮع‬1‫ رح اوﺧﺬ‬+*‫اﻟﻘﺮاءﺗ'ن اﻟ‬
iadeal ‫ﻤﮫ ال‬1 ‫ اﻟﺜﺎﻧﻴ'ن ﻋﺸﺎن‬3‫ﺎن ﻣﻌﮫ أﻋﺮاض ﻳﻔﻀﻞ ا\ﻲ أﺗﺄﻛﺪ وأﻋﻤﻞ ﻓﺤﺺ ﻣﻦ ال‬Y‫( و‬Random glucose) ‫ﻟﻮ أﻧﺎ ﻋﻤﻠﺖ‬

HBA1C Testing
— A1C refers to the % of glycosylation of the hemoglobin A1C chain and approximates
average blood glucose levels over the previous two to three months.
— A1C was first included in the ADA guidelines as a diagnostic test for diabetes in 2010.
— A1C is not recommended as a tool for diagnosing gestational diabetes ( it is a less
reliable marker of glycemia during pregnancy as physiological changes may lower
HbA1c levels).
— A1C may be misleading in some clinical settings (see next slide)
◦ We may use the fructose amine test instead of the AbA1C test in these cases.
 Diabetes Screening Diabetes Screening “Who Should Be Screened”
TYPE 1 DIABETES The American Diabetes Association (ADA) recommendations:
— Screening for type 1 DM in asymptomatic low-risk individuals is not — Type 2 diabetes testing should be done in all asymptomatic adults (above 18 years

recommended. old) who are overweight (BMI ≥25 kg per m 2 ) who have ≥1 of the following diabetes
risk factor:
— However, in patients at high risk (eg, those who have first-degree
ü Physical inactivity
relatives with type 1 DM), it may be appropriate to perform annual ü First-degree relative with type II diabetes
screening for anti-islet antibodies before the age 10 years, along with 1 ü High-risk race/ethnicity (i.e., African American, Latino, Native American, Asian American, and Pacific Islander)
additional screening during adolescence. ü Women who delivered a baby >9 lb or were diagnosed with GDM
ü HDL-C <35 mg/dL or/and TG >250 mg/dL
TYPE 2 DIABETES ü Hypertension (≥140/90 mm Hg or on therapy)

— Screening is recommended for type 2 diabetes because reliable tests ü A1C ≥5.7%, IGT, or IFG on previous testing (repeat the test annually)
ü Conditions associated with insulin resistance: severe obesity, acanthosis nigricans, PCOS
are available, and lifestyle changes and medications reduce
ü Cardiovascular disease (CVD) history
progression and adverse sequelae of the disease, even in persons who
are initially asymptomatic. — Testing should begin at age 35 if no risk factors. (ADA 2022)
— If normal results: repeat testing in ≥3-yr intervals

Key Points for Practice

— Prediabetes is not a diagnosis but rather an opportunity to
prevent or delay a future diagnosis of type 2 diabetes.
Prediabetes — Intensive lifestyle programs are the most effective intervention
for preventing or delaying a diagnosis of diabetes in patients
with prediabetes.
— In patients with prediabetes, Metformin therapy will slow the
progression to type 2 diabetes, although less effectively than
lifestyle programs over time.

Prediabetes testing
—can be done using A1C, FPG, or 2-h PG after 75-g OGTT.
ü Impaired Fasting Glucose (IFG)
FPG = 100 to 125 mg/dl ( 5.6 to 6.9 mmol/L)
ü Impaired Glucose Tolerance (IGT)
2 hr pp = 140-199 mg/dl ( 7.8-11 mmol/L)
ü HbA1C = 5.7%-6.4%
— Screening for and treatment of modifiable CVD risk factors
(obesity, hypertension, smoking and dyslipidemia) suggested
— At least annual laboratory monitoring for the development of — Age <60 years
diabetes in those with prediabetes is suggested
Clinical evaluation of DM patients
Strategies for Preventing or Delaying Type 2 Diabetes in Prediabetes
Ø Strong evidence supports lifestyle interventions to delay or prevent diabetes.
Programs that include diet, weight loss, and exercise reduce type 2 diabetes diagnoses by up to
58% over three years.
The ADA recommends lifestyle modification as the primary intervention, goals as follow:
— Sustained weight loss of at least 7% of body weight.
— at least 150 minutes of moderate-intensity exercise weekly.
— Smoking cessation
Ø Medications can delay or prevent type 2 diabetes but are less effective than lifestyle programs.
● Metformin has the strongest evidence, whereas some other anti-DM medications have some
evidence of benefit.
● Initially, Metformin is nearly as effective as lifestyle modification; however, over time, lifestyle
interventions demonstrate clear superiority.
Consider metformin therapy for type 2 diabetes prevention, especially in the presence of:
— BMI >35 kg/m2
— Women with prior GDM
— in whom lifestyle interventions fail to improve glycemic indices..
Signs and symptoms
— Many patients with type 2 diabetes are asymptomatic.
Ø Clinical manifestations of hyperglycemia include the following:
— Classic symptoms: Polyuria, polydipsia, polyphagia, and weight loss.
● Other symptoms that may suggest hyperglycemia include
Ø Blurred vision
Ø Lower-extremity paresthesias
Ø Yeast infections
Hypoglycemia symptoms: (assess in patients taking insulin or insulin secretagogues)
— Pallor Focused Diabetes History
— Tremor
— Dizziness or lightheadedness
— Sweating — How and when was the diagnosis of DM and what was the initial management ( lifestyle
— Hunger or nausea & pharmacological)?
— Palpitation
— Difficulty concentrating
— Current status
— Fatigue ü Symptoms of out-of-control
— Irritability or anxiety Polyuria, polydipsia, polyphagia, nocturia, weight loss, fatigue, recurrent infections
— Headache
(UTIs, vaginal candidiasis), and delayed wounds healing.
— Tingling or numbness of the lips, tongue or cheek
— Confusion, unusual behavior or both, such as the inability to complete routine tasks ü Current DM medications, compliance to medications, and any S.Es
— Loss of coordination ü Compliance with lifestyle changes (diet & physical activity)
— Difficulty speaking or slurred speech
ü Self glucose monitoring.
— Blurry vision
— Muscle weakness
— Drowsiness
— Severe hypoglycemia may cause Convulsions or seizures, Unconsciousness, and Death.

— Complications
Acute
— Hypoglycemia / hypoglycemic symptoms, If so, when, how often, and how does the patient treat
these episodes
— Hx of DKA or NKHH ( ER visit or admission)
Macrovascular
— When was the patient's HbA1c last measured, and what was it
— CVS: chest pain (cardiac), hx of CAD ,excertional dyspnea, orthopnea, PND, L.L edema — What is the patient’s immunization history - Eg, influenza,
— Cerbrovascular: weakness, speech difficulty, hx of stroke/TIA
— Intestinal : severe abdominal pain postprandial, vomiting.. pneumococcal, hepatitis B, tetanus, herpes zoster
— PAD: intermittent claudication, or a history of vascular bypass
— Does the patient have hypertension; what medications are
Microvascular
— Retinopathy: last dilated eye examination, and what were the results, any blurred vision , red taken
painful eye
— Nephropathy: last measurements of urine protein and serum creatinine levels , any urinary — Does the patient have CAD
symptoms
— Neuropathy: — What are the patient's most recent lipid levels; is the patient
ØPeripheral symmetrical : numbness, tingling or pain in extremities
ØAutonomic: gastroparesis, impotence, orthostatic hypotension, impaired sweating…
taking lipid-lowering medication
ØMononeuropathy: cranial nerve palsy, carpal tunnel… — Family history of DM or chronic disease
Foot ulcer or amputations
 Physical Examination Diabetic Foot Examination
— Early in the course of diabetes mellitus, the physical examination findings are likely to
be unrevealing. Ultimately, however, end-organ damage may be observed.
— A diabetes-focused examination includes
ØVital signs, BMI, waist and hip circumferences.
ØFunduscopic examination( ‫ اﻟﻠﻲ ﺑﻧﺷوف ﻓﯾﮫ ال‬optic nerve)
Ølimited Vascular, Cardiac, and Neurologic examinations
ØFoot assessment

Diabetic Foot Examination

Inspection
— Inspect the lower limbs, and look at the posterior aspect of each leg and between each of the toes for hidden ulcers or pathology.
— Note Skin color and if dry or shiny waxy
Peripheral cyanosis: bluish discoloration of the skin, may be present in PVD due to poor perfusion.
Ø
Peripheral pallor: a pale color of the skin that can indicate poor perfusion.
Ø
— Swelling (edema)
— Muscle atrophy
— Varicose veins
— Ulcers (Location, Base, Floor, Size, Color)
ØVenous ulcers: typically, large and shallow ulcers with irregular borders that are only mildly painful. These ulcers most commonly
develop over the medial aspect of the ankle.
ØArterial ulcers: typically small, well-defined, deep ulcers that are very painful. These ulcers most commonly develop in the most
peripheral regions of a limb (e.g. the ends of digits).
— Missing limbs, toes, fingers: due to amputation
— Scars: may indicate previous surgical procedures (e.g. bypass surgery) or healed ulcers.
— Hair loss: occurs due to chronic impairment of tissue perfusion in PVD.
— Nails - yellow thick deformed, brittle nails
— Specific skin findings in DM- Necrobiosis lipodica, Diabetic dermatopathy
— Deformity (e.g. Charcot arthropathy)
Charcot arthropathy — Necrobiosis lipoidica is a
rare, chronic granulomatous
— involves the progressive degeneration of a weight- disease of the skin. Skin
bearing joint due to peripheral neuropathy. involvement usually begins as
red-brown papules, plaques, or
— The typical clinical features of a Charcot’s joint include:
nodules and rapidly progresses
ØEffusion to yellow-brown, atrophic,
telangiectatic plaques, seen
ØDistortion
more in type I DM.
ØOverlying erythema
— Diabetic dermopathy,
ØLoss of joint function spots or pigmented pretibial
patches, it is a skin condition
usually found on the lower legs
of people with diabetes.

Palpation
— Temperature
— Place the dorsal aspect of your hand onto the patient’s lower limbs to assess and
compare temperature:
— In healthy individuals, the lower limbs should be symmetrically warm, suggesting adequate
perfusion.
— A cool and pale limb is indicative of poor arterial perfusion.

— Capillary refill time

◦ On the skin or in the nails

— Pulses
— Palpate the posterior tibial and dorsalis pedis pulse to briefly assess peripheral perfusion.
Absence of peripheral pulses is suggestive of peripheral vascular disease.
ØPosterior tibial pulse
located posterior and inferior to the medial malleolus of the tibia.
ØDorsalis pedis pulse
located over the dorsum of the foot, lateral to the extensor hallucis longus tendon, over
the second and third cuneiform bones.
 — Sensation
Pinprick test
ability to feel a pinprick
Monofilament
1. Provide an example of the monofilament sensation on the patient’s arm or sternum.
2. With the patient’s eyes closed, apply the monofilament to each of the following locations in
turn:
◦ The pulp of the hallux.
◦ The pulp of the third digit.
◦ Metatarsophalangeal joints 1, 3, and 5.

3. When applying the monofilament to each area:

◦ Ask the patient to report when they feel the monofilament touch their foot.
◦ Press the monofilament against the skin until it bends slightly (this will ensure that only 10g of
pressure is applied).
◦ Hold the monofilament against the skin for 1-2 seconds.
◦ Avoid calluses and scars as they have a reduced level of sensation that is not representative of the
surrounding tissue.

Vibration sensation
1. Ask the patient to close their eyes and to let you know both when they can detect vibration and when it
stops.
2. Tap a 128 Hz tuning fork and place it onto the patient’s sternum to check they can feel it vibrating.
3. Tap the tuning fork again and place it onto the interphalangeal joint of the patient’s big toe. If the patient
can accurately identify when the vibration begins and when it stops at this point in both lower limbs, the
assessment is complete.
4. If vibration sensation is impaired at the interphalangeal joint of the patient’s big toe, continue to
sequentially assess more proximal joints (e.g. metatarsophalangeal joint of the big toe → ankle joint →
knee joint) until the patient can accurately identify vibration.

Proprioception (joint position sense).

1. Begin assessment of proprioception at the interphalangeal joint of the big toe by holding the distal
phalanx of the big toe by its sides. (don’t touch the nails)
2. Demonstrate movement of the big toe “upwards” and “downwards” to the patient whilst they watch.
3. Ask the patient to close their eyes and state if you are moving their big toe up or down.
4. Move the big toe up or down 3-4 times in a random sequence to see if the patient can accurately identify
joint position with their eyes closed.
5. If the patient is unable to correctly identify the direction of movement, continue to sequentially assess
more proximal joints (e.g. metatarsophalangeal joint of the big toe → ankle joint → knee joint).
 Ankle-jerk reflex
— Assess the ankle-jerk reflex in each of the patient’s lower limbs.
— The ankle jerk reflex may be absent in advanced peripheral neuropathy.

1. With the patient on the examination couch support their leg so that their hip
is slightly abducted, the knee is flexed, and the ankle is dorsiflexed.
2. Tap the Achilles tendon with the tendon hammer and observe for a
contraction in the gastrocnemius muscle with associated plantarflexion of the
foot.

Assess the patient’s gait

— Patients with peripheral neuropathy may demonstrate
a conservative gait strategy in which their walking speed
is reduced and their foot stance is broadened. The
development of foot drop is also more common in
diabetic patients, which can result in a high-stepping
gait.

Inspect the patient’s footwear

 Investigations Management of DM
— HBA1C every 3-6 months
◦ Every 3 months and every 6 months if the patient is controlled without insulin and
has a good lifestyle.
— Check feet daily+ annual Comprehensive foot exam ( podiatry referral)
— Annual Dilated eye examination The goals of treatment for diabetes are to prevent
or delay complications and maintain quality of life.
— Annual dental check
— Annual microalbuminuria, Urine albumin-to-creatinine ratio (spot urine), • Lifestyle modification and diabetes
Serum creatinine (with estimated glomerular filtration rate [eGFR]) education are the core of management.
— Annual fasting lipid profile
• We must pay attention to BP, lipid, CV, and
kidney management in DM patients.
Ø In patients with type 1 diabetes we also measure, periodically:
— Serum thyroid-stimulating hormone (TSH)
— Celiac antibodies to screen for celiac disease

More or less stringent targets may be appropriate if can be achieved without

Glycemic Targets for Nonpregnant Adults With Diabetes
A1C
Preprandial capillary PG
Peak postprandial capillary PG
significant hypoglycemia or adverse events
More stringent target (<6.5%) Less stringent target (<8%)
• Short diabetes duration • Severe hypoglycemia history
<7.0% • Long life expectancy • Limited life expectancy
Lowering A1C below or around 7.0% has been shown to reduce: • No significant CVD/vascular complications • Advanced Microvascular or macrovascular
• Microvascular complications complications
• Macrovascular disease • Extensive comorbidities
80-130 mg/dL (4.1-7.2 mmol/L) • Long-term diabetes in whom general A1C target
difficult to attain
<180 mg/dL (<10.0 mmol/L)
Postprandial glucose measurements should be made 1-2 hours after the
beginning of the meal Individual risk stratification is highly recommended.

Individualize targets based on: Age/life expectancy For example:

Comorbid conditions In patients with advanced type 2 diabetes who are at high risk for cardiovascular disease, lowering
Diabetes duration HbA1c to 6% or lower may increase the risk of cardiovascular events.
Hypoglycemia status
Individual patient considerations ‫ﻞ ﻣﺎ ﺷﺪﻳﺖ ﻋﻠﻴﮫ‬M ‫ﺎظ ﺑﺨﻔﻒ ﻣﻌﮫ ﺑﺎﻟﻌﻼج ﻻﻧﮫ‬C BA‫ﺑﺎﻟﻌﻤﺮواﻟﺴﻜﺮي ﻋﻨﺪﻩ ﻣﻦ زﻣﺎن وﻋﻨﺪﻩ ﻛﻮﻣﻮر>ﻴﺪﻳ‬+*‫ﺾ اﻟﻜﺒ‬$‫اﳌﺮ‬
Known CVD/advanced microvascular complications
.‫ﺪﻩ ﺳﻮء‬$‫ﺎظ ﺑﺰ‬C‫ﺎ ا[\ﺎﻧ]ﻴﺔ و‬Z‫ﺪ ﺑﺎﻋﺮاﺿ‬$‫ﺔ و>ﺰ‬$‫ﺪ ﺑﺎﻷدو‬$‫ اﻧﺎ ﻗﺎﻋﺪ ﺑﺰ‬BS‫ﻌ‬R

Management
— Diabetes mellitus is a complex and challenging disease requiring daily self-
management decisions.
— Goals of treatment are as follows:
Ø Microvascular (ie, eye, and kidney disease) risk reduction through control of
glycemia and blood pressure
Ø Macrovascular (ie, coronary, cerebrovascular, peripheral vascular) risk reduction
.‫ﺧﻠص وﺿﻌﮫ ﻛﺛﯾر ﺳﻲء ﻟﻛن ﻻ اﻻﻧﺳوﻟﯾن ھو اﻓﺿل ﻋﻼج ﻟﻠﺳﻛري ﻣﻊ ﻻﯾف ﺳﺗﺎﯾل ﻻﻧﮫ ھو اﻻﻗرب ﻟﻠطﺑﯾﻌﻲ‬
through control of lipids and hypertension, smoking cessation, and aspirin
therapy
Ø Metabolic and neurologic risk reduction through control of glycemia.
The EASD/ADA position statement contains 7 key points:
1. Individualized glycemic targets and glucose-lowering therapies
2. Diet, exercise, and education as the foundation of the treatment program
3. Use of Metformin as the optimal first-line drug unless contraindicated
4. After Metformin, the use of 1 or 2 additional oral or injectable agents, with a goal of
minimizing adverse effects if possible
5. Ultimately, insulin therapy alone or with other agents if needed to maintain blood
glucose control
‫ اﻟﻧﺎس ﺑﺗﻔﻛر اﻧﮫ ﻟو ﺑﻠش ﯾوﺧذ اﻧﺳوﻟﯾن‬,‫– ﺑﻌض اﻟدراﺳﺎت ﺑﺗﺣﻛﻲ اﻧﮫ ﻛل ﻣﺎ ﺑﻠﺷﻧﺎ ﺑﺎﻻﻧﺳوﻟﯾن اﺑﻛر ﺑﻛون اﺣﺳن‬
6. Where possible, all treatment decisions should involve the patient, with a focus on
patient preferences, needs, and values
7. A major focus on comprehensive cardiovascular risk reduction

Management/Lifestyle Weight reduction

Lifestyle management is a fundamental aspect of diabetes care and includes :
— Physical activity and Exercise ( 150 min/weak or 30 min/day at least 3 times/week) — Reduction of 5-10% in weight can have a major
Smoking cessation counseling,
—
— Weight reduction.
impact on the clinical course of type 2 DM.
— Avoid stress.
Psychosocial care.
—
— Normal or near normal weight will:
— Diet and Nutrition:
P Decrease total calorie intake (500 k cal deficit diet) a) Optimize insulin sensitivity
Divide meals to small frequent meals; 5 meals (3 main meals + 2 snacks)
P
b) Minimize insulin requirement
P Avoid sugar-sweetened beverages (including fruit juices)
P High fiber diet including vegetables, fruits, legumes, whole grains c) Minimize cardiovascular risks
P Avoid fruits rich in sugar like (grapes, figs), one type of fruit is allowed in the day.
P Low fat, Encourage intake of monounsaturated and polyunsaturated fat.
P Limit sodium intake to 2,300 mg/day.
— Moderation in alcohol consumption (< 21 units/week for men and < 12 units for women).
 — The majority of type 2 diabetic patients require oral hypoglycemic agents.
ORAL HYPOGLYCEMIC AGENTS & INSULIN — At time of diagnosis pancreatic function is 50% of normal.
— Choice of pharmacologic therapy should be based on patient-centered approach,
considering
q Efficacy, Cost
q Potential side effects , Effects on weight
q Comorbidities
q Hypoglycemia risk
q Patient preferences
Insulin is eventually needed for many patients due to the progressive nature of type 2
diabetes
1) Failure of dietary and medication compliance
2) Final exhaustion of beta cells.

ORAL HYPOGLYCEMIC AGENTS CLASSES Incretin-based GLP-1 receptor

therapies agonists
Exenatide
Liraglutide
Activation of the GLP- ↓
1 receptor so
No 1.0-2.0% Mild transient nausea, vomiting,
& diarrhea, headache and
Should not be used
in history of
MAIN CLASS NAMES/ MOA WT HYPOGL HbA1c S.Es Cautions Semaglutide stimulates insulin, dizziness pancreatitis
CATEGORY EXAMPLES EFFECT YCEMIA reduction reduce Albiglutide suppresses glucagon
cardiovascular Dulaglutide secretion, and slows
GLP-1 and GIP gastric emptying.
Insulin Biguanides Metformin ↑ muscle glucose Neutral or NO 0.8-2.0% GI S.E (nausea, Contraindication in mortality
are glucose- Decrease appetite
sensitizers uptake ↓ vomiting, diarrhea , severe hepatic or renal
dependent DPP4 inhibitors Sitagliptin Inhibit enzymic Neutral No 0.4-1.0% Angioedema, urticaria Acute Should not be used
‫ ↓ اﺣﻔظوه ﻛﺎﻣل ﻣﻣﻛن ﯾﯾﺟﻲ‬hepatic cramping), B12 insufficiency (eGFR˂ 30,
insulin Vildagliptin degradation of ↓ pancreatitis. Nasopharyngitis. in history of
counseling ‫ ﻋﻠﯾﮫ ﺳﺗﯾﺷن‬gluconeogenesis deficiency, lactic severe infection,
secretion Saxagliptin incretins ( GIP, GLP-1) Risk for heart failure (saxagliptin, pancreatitis.
acidosis (rare) dehydration, and heart
failure. Major operation Linagliptin alogliptin) Dose titration in
or iodine-contrast use Gemigliptin severe hepatic or
within 48 hours Alogliptin renal insufficiency
Teneligliptin
Anagliptin
Thiazolidinediones Pioglitazone [Actos] Activate PPAR-ᵧ ↑ No 0.6-1.5% Edema, anemia, bone Heart failure, severe Inhibitors of Alpha- Acarbose Inhibit digestive ↓ No 0.4-1.0% GI side effects (flatulence, Severe hepatic or
/TZDs (Glitazones) Rosiglitazone [Avandia] receptor, ↑ Insulin fracture, heart failure hepatic or renal CHO glucosidase voglibose enzyme diarrhea, bloating) renal insufficiency,
sensitivity (muscle, insufficiency inhibitor chronic inflammatory
absorption
adipose tissue), ↓ ‫ﺑﺣطم اﻻﻧزﯾﻣﺎت اﻟﻠﻲ ﺑﺗﻛﺳر‬ ,‫ ﺗﺧﯾل ﻛﻣﯾﺔ اﻟﺳﻛر واﻟﻛﺎرﺑز ﺑﺎﻟﻘوﻟون‬bowel disease with
(last choice ‫اﻟﺳﻛر وﺑﺗﺳﺎﻋد ﻋﻠﻰ‬ ‫ ﻓﺎﻋراض ﻛﺛﯾرة‬malabsorption,
hepatic
gluconeogenesis (‫وﻏﯾر ﻣﺳﺗﺧدم‬ ‫اﻣﺗﺻﺎﺻﮫ ﺑﻔظل اﻟﺳﻛر‬ severe infection
Insulin Sulfonylurea Gliclazide Stimulate insulin ↑ Yes 1.0-2.0% Severe hepatic or renal GI ‫ﻣوﺟود ﺑﺎل‬
secretagogues ‫ر‬‫ﺛ‬‫ﻛ‬ ‫أ‬ ‫م‬ ‫د‬‫ﺧ‬‫ﺗ‬‫ﺳ‬‫ﻣ‬ ‫و‬ ‫ر‬ ‫و‬ ‫ﮭ‬‫ﺷ‬‫ﻣ‬ Glipizide secretion from B-cells insufficiency, secondary
glyburide of pancreas failure
Glimepiride ↓ Renal SGLT2 inhibitors Dapagliflozin Selective sodium- ↓ No 0.5–1.1% Genitourinary tract infections, renal impairment (ie,
glibenclamide glucose ‫ دواء ﺟدﯾد وﻓﻌﺎل‬canagliflozin glucose transporter-2 polyuria, dehydration, DKA estimated glomerular
Meglitinide Repaglinide Stimulate insulin ↑ Yes (less) 0.6-2.0% Severe hepatic or renal Ipragliflozin inhibitors ‫اﻟﻣرﯾض ﻻزم ﯾﺷرب ﻛﻣﯾﺎت ﻛﺑﯾرة ﻣن اﻟﻣﻲ‬ filtration rate [eGFR]
reabsorption
derivatives Nateglinide secretion / shorter- insufficiency Empagliflozin ‫ ﺣﺗﻰ‬,‫ﻋﺷﺎن ﻣﺎ ﯾﺻﯾر ﻣﻌﮫ اﻟﺗﮭﺎﺑﺎت‬ < 60
(Prandial glucose Mitiglinide acting ertugliflozin ‫ﺑطﻠﻊ اﻟﺳﻛر ﺑﺎﻟﺑول‬ ‫ﺑرﻣﺿﺎن ﺑﻧﺣﻛﯾﻠﮫ ﯾﻔطر وﯾظل ﯾﺷرب ﻣﻲ‬
regulators)
 INSULIN SENSITIZERS
Biguanides: (↓ HbA1C 0.8-2.0%) — GLP-1 receptor agonists reduce cardiovascular mortality, all-
q Metformin is the only biguanide in clinical use.
q Metformin is the drug of choice for treatment of type 2 diabetic cause mortality, and stroke in people with CVD. (SOR: A,
patient. consistent, good-quality patient-oriented evidence.)
q Metformin lowers basal and postprandial plasma glucose levels
q It does not cause hypoglycemia, No weight gain ( maybe weight loss) — SGLT-2 inhibitors reduce cardiovascular mortality, all-cause
and improve lipid profile.
q Metformin decrease blood glucose by: mortality, and hospitalization from heart failure in people
üdecreasing hepatic gluconeogenesis with CVD. (SOR: A, consistent, good-quality patient-oriented evidence).
üdecreasing intestinal absorption of glucose
üincreasing peripheral glucose uptake and utilization.
q Daily dose 1.5 – 2.5 g
q Side effects = diarrhea, nausea, lactic acidosis . Long term use may be
associated with vitamin B12 deficiency,
q Stop if doing a radiologic contrast study within 48 hours.
(avoid in patient with renal, hepatic and unstable heart failure).
53

‫اﺣﻔظ ﻛﻣﻘﺎرﻧﺔ ﺑﯾﻧﮭم‬

INSULIN
Basal Insulin accounts for approximately 50% of total insulin
secreted each day whereas the remaining 50% of the
insulin is secreted in response to meals.
‫ﯾﻔرز ﻋﻠﻰ ﻣدار اﻟﯾوم ﺑﻐض اﻟﻧظر اﻧﺗت ﻣﺎﻛل أو ﻷ‬Basal insulin ‫ال‬
Types of Insulin:
1) Rapid-acting analog e.g Aspart, Lispro, glulisine
2) Short-acting e.g Regular
3) Intermediate-acting e.g NPH (isophane), Lente
4) Long-acting e.g Glargine, Detemir, degludec (basal insulin)
5) Premixed Insulin

55
 Gestational D.M (GDM)

For basal insulin

‫ﻮ ﺑﻮﺧﺬ‬J‫ ﻣﻊ ﻋﻘﺎرب اﻟﺴﺎﻋﺔ و‬BA@‫ ﻣﺜﻼ ﻳﻤ‬,‫ﻘﻦ‬:9‫اﻣﺎﻛﻦ ا‬54‫ﻐ‬2 ‫ﺾ‬0‫ﻲ ﻟﻠﻤﺮ‬+‫داﺋًﻤﺎ ﺑﻨﺤ‬
‫ ﺑﻄﻨﮫ‬RQ ‫ن‬4‫ﺴﻮﻟ‬O‫اﻻ‬

Screening for gestational diabetes is usually performed during

— Women with gestational diabetes mellitus (GDM) who have the second trimester (24 – 28 weeks of pregnancy). However,
in high-risk women, the screening can be done early in the
fasting hyperglycemia have a three- to four-fold increased risk of
pregnancy.
infant malformations.
— The goal of screening is to reduce maternal and fetal Ø ADA, ACOG and CDC advise screening pregnant women in their
complications such as preeclampsia, cesarean delivery, first trimester if they have risk factors for developing type 2
congenital malformations, macrosomia (and later diabetes or GDM, including obesity, advanced maternal age
childhood/adolescent overweight), shoulder dystocia, nerve (older than 35 years), history of GDM, family history of
palsy, bone fracture, jaundice, and infant death. diabetes, and belonging to a high-risk ethnic group.
Ø However, AAFP and the USPSTF recommend screening for
GDM only after 24 weeks' gestation.
Gestational D.M Diagnosis (at 24–28 weeks of gestation) Glycemic Targets in Pregnancy
The ADA has recommended the use of either
Ø The one step approach: (75-g OGTT) v Fasting and postprandial self-monitoring of blood glucose are
The diagnosis of GDM is made when any of the following is met or exceeded : recommended in pregnancy to achieve optimal glucose levels.
Fasting: 92 mg/dL (5.1 mmol/L) Glucose targets are
1 hour: 180 mg/dL (10.0 mmol/L)
2 hour: 153 mg/dL (8.5 mmol/L). — fasting plasma glucose <95 mg/dL (5.3 mmol/L)
Or and either
Ø The Two step approach: — 1-h postprandial glucose <140 mg/dL (7.8 mmol/L)
Challenge test: 50 g glucose load then test at 1 hr (non fasting)
or
If > 135-140, perform a fasting 100-g OGTT.
The diagnosis of GDM is made if at least two of the following 4 plasma glucose levels — 2-h postprandial glucose <120 mg/dL (6.7 mmol/L).
(measured during OGTT) are met or exceeded :
Fasting: 95 mg/dL (5.3 mmol/L)
1 hour: 180 mg/dL (10.0 mmol/L) v In majority gestational D.M resolve after pregnancy but is likely to
2 hour: 155 mg/dL (8.6 mmol/L) recur.
3 hour: 140 mg/dL (7.8 mmol/L)

GDM Management
— Lifestyle change is an essential component of management of GDM and may suffice for
ACUTE COMPLICATIONS
the treatment of many women.
Øshould consume a high-nutrient and high-fiber diet and avoid a high-sugar and high- 1) Diabetic Ketoacidosis (DKA)
fat diet. 2) Nonketotic Hyperosmolar Hyperglycemia (NKHH)
ØRegular physical activity helps reduce blood glucose levels and maintain weight gain
during pregnancy. 30 minutes of moderate exercise are recommended, including 3) Hypoglycemia
walking, cycling, and swimming. 4) Lactic acidosis
— About 30% of diabetes during pregnancy is not controlled by diet and exercise. In these
cases, blood glucose levels must be managed by insulin injections.
— Some physicians may advise oral diabetic medicines. However, all oral agents lack long-
term safety data and it is not clear whether these medicines can control blood glucose
levels as effectively as injectable insulin.

— Another vital thing is to closely monitor the growth and development of the baby
through frequent ultrasounds and other related tests.

64
SIGNS & SYMPTOMS KETOACIDOSIS (DKA) NONKETOTIC HYPEROSMOLAR
Hypoglycemia in Diabetic Patient
More common Less common
mortality rate 0.2-2% much higher 5-20%
occurs mainly in type 1 diabetes but it
is not uncommon in some type 2
most commonly seen in type 2 DM — Management:
diabetes Ø(Mild) oral rapidly absorbed food
Preceding infection , missed insulin, stress Infection, stroke or myocardial
infarction Ø(Severe) I.V solution of hypertonic glucose (Dextrose Saline)
DEHYDRATION ++++ ++++ severe Profound dehydration, up
to an average of 9L
—Never Give Oral Glucose In Severe Cases as it may precipitate
STUPOR, COMA mild confusion; frank coma is Some alteration in consciousness Aspiration Pneumonia
uncommon
KUSSMAUL BREATHING Present Absent
— Hypoglycemia corrected by glucose last only 1-2 hrs therefore
BLOOD GLUCOSE over 250 mg/dL 600 mg/dL or greater a meal with complex CHO and protein must follow within that
SERUM OSMOLALITY 290 mOsm/L or greater 320 mOsm/kg or greater
period.
KETOSIS in blood ketonemia and ketonuria. Absent — Glucagon injection (1mg ) I.M also helpful
ACIDOSIS pH less than 7.3 pH greater than 7.3

CHRONIC COMPLICATIONS
Coronary Heart Disease
Macrovascular Complications of Diabetes
(Atherosclerotic vascular disease) Ø Risk for CHD is 2-4 times greater in patients with diabetes than it is in individuals
1) Coronary artery disease without diabetes
2) C.V.A
Ø Up to 75% of type 2 DM & 35% of type 1 DM die from CVD
3) Peripheral vascular dis.
Ø CVD is the largest contribute to the direct and indirect costs of diabetes
4) Intestinal ischemia
5) Renal artery stenosis
* Up to 80% of pts. with type 2 diabetes will develop Ø Control of hypertension, aspirin therapy, and lowering of LDL cholesterol levels are
or die of macrovascular disease. vitally important in reducing CHD risk.
Microvascular Complications of Diabetes
1) Diabetic nephropathy
2) Peripheral and Autonomic neuropathy
3) Diabetic retinopathy

67 38
 Hypertension & DM Dyslipidemia in DM
Ø Hypertension role in increasing microvascular and macrovascular risk in patients with Ø Trials have shown that the use of statins is effective for primary
diabetes mellitus has been confirmed
and secondary prevention of coronary heart disease (CHD) events
Target BP (JNC 8 + ADA ) in patients with diabetes.
Ø in most DM patients is :140/90 Ø For individuals with Type 1 DM who are at high or very-high risk,
Ø For patients with a high risk of cardiovascular a blood pressure target of <130/ 80 mmHg
may be appropriate. statins are recommended.
Ø if proteinuria and renal insufficiency : target BP is < 125/75 Ø For patients with type 2 diabetes mellitus
— at very-high risk (10-year risk of CV death ≥10%), an LDL-C
Ø The ADA recommendations blood pressure measurement “at every routine clinical care
visit” reduction of at least 50% from baseline and an LDL-C goal of
Ø Medication either ACE inhibitor or ARBs, because of their proven renal protection effects in below 1.4 mmol/L (<55mg/dL) is recommended.
patients with diabetes.
(CCB : in cases of intolerance or contraindication to ACE inhibitors) — For those at high risk (10-year risk for CV death of 5% to <10%),
an LDL-C reduction of at least 50% from baseline and an LDL-C
goal of below 1.8 mmol/L (<70 mg/dL) is recommended.

Diabetic Nephropathy
Diabetic Nephropathy
Ø Diabetic nephropathy occurs in 20-40% of patients with diabetes
— Screening
Ø DM is the most common single leading cause of end-stage renal disease (ESRD) Ø Annually measure urine albumin excretion in type 1 patients with ≥5-yr diabetes duration,
Ø Optimize glucose and BP control to reduce the risk for or slow the progression and all type 2 patients starting at diagnosis
— Treatment
of nephropathy
vNormal BP, normal urinary albumin to-creatinine ratio (<30 mg/g creatinine), and normal
Ø The most Useful screening test is the albumin: creatinine ratio(AC Ratio) on eGFR = treatment with ACRI or ARB is not recommended
the 1st morning urine sample. More than one positive test is required over a vNon-pregnant with modest elevations (30-299 mg/24 h) or higher levels (≥300 mg/24 h) of
few weeks or months urinary albumin excretion = Use ACEI or ARB (but not in combination)

Ø Microalbuminuria (persistent albuminuria in the range of 30-299 mg/24 hr) is

(When using ACEI, ARB, diuretic should monitor creatinine and potassium levels)
the earliest stage of diabetic nephropathy and a marker of CVD risk
Ø ACE inhibitors usage is associated with significant reduction in progress to overt
proteinuria & increase regression to normoalbuminuria
 Diabetic Retinopathy (DR) Diabetic Neuropathy
v D.R is the leading cause of blindness v Main types:
v diabetic patients have 10% chance of acquiring blindness from retinopathy 1) Distal symmetrical polyneuropathy (irreversible)
v Glaucoma, cataracts and other disorders of the eye occur earlier & more
frequently in people with diabetes 2) Mononeuropathy & Multiple mononeuropathy (may be reversible)
3) Autonomic neuropathy
Screening
In type 2 DM start screening at time of diagnosis v Up to 30% of diabetic develop neuropathy
— If no retinopathy for ≥1 eye exam: consider exams every 2 yrs
— If retinopathy: annual exam v Symptoms : Numbness, parasthesia, pain, absence sensation, ulcer , allodynia , may be
— Retinopathy progressing or sight threatening: more frequent exams asymptomatic (50%).

— Optimize glycemic control, BP control and lipid control.

— Laser photocoagulation is indicated in patients with PDR, macular edema and
some cases of NPDR

Diabetic Neuropathy Diabetic Foot

v Neuropathic Pain Management: v Foot ulcer occurs in 5-10% of diabetic patient
— Low-dose tricyclic antidepressants (TCA) v Three pathophysiologic process result in injury predisposition + potential amputation:
— Duloxetine a) Neuropathic ulcer b) Ischemia c) Sepsis
— Anticonvulsants (eg, phenytoin, gabapentin, carbamazepine)
— Topical capsaicin — All individuals with diabetes:
— Various pain medications, including NSAIDs. qAnnual foot exam to identify risk factors predictive of ulcers and amputations
qAssessment of foot pulses, loss of protective sensation (LOPS) testing
qProvide foot self-care education.

v Foot self-care education: daily inspection , cleaning & drying, nails cutting, low-heeled
shoes of soft leather, smoking cessation, avoid hot objects, never go barefoot, taking advise
of doctors for any foot problem. In patients with advanced neuropathy, water temperature
must be checked by a companion or with a thermometer
 Continuous glucose monitors (CGMs)
— Used for the self-management of diabetes mellitus and have a subcutaneously
inserted sensor that measures glucose in the interstitial fluid and transmits the
result to a receiver.
Diabetes and technology — Used is adults and children with type 1 diabetes and adults with insulin-treated
type 2 diabetes.
* — The FreeStyle Libre 14-day system is an intermittently scanned or “flash” CGM
Diabetes Future that was approved by the U.S. FDA in 2017.

CGMs Closed loop system “Future treatment for DM type 1”

— It displays glucose values when the sensor is
scanned with the receiver. — The Food and Drug Administration has approved two
— The sensor is placed on the posterior upper arm artificial pancreases for people with type 1 diabetes who
— Real-time CGMs measure glucose every one to are age 14 and older.
five minutes and issue alarms when glucose — The device, also called a closed loop system, is implanted
values are too high or low. in the body, links a continuous glucose monitor to an
— Some brands may need to be calibrated by self- insulin pump. The monitor checks blood sugar levels
monitoring of capillary blood glucose (SMBG), every five minutes. The device automatically delivers the
which uses a finger stick and test strips correct amount of insulin when the monitor shows that
it's needed.
 Islet cell transplantation
— Researchers are experimenting with islet cell transplantation.
— This provides new insulin-producing cells from a donor pancreas.
— This experimental procedure had some problems in the past, but
new techniques and better drugs to prevent islet cell rejection may
improve its chances of becoming a successful treatment.

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