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2. 
 A metabolic disease characterized by hyperglycemia
with or without glycosuria resulting from defects in
insulin secretion (Type I), insulin action (Type II).
DM

3. 
 Type-1 DM :
 insulin-dependent DM
 juvenile-onset diabetes
 Type-2 DM :
 non-insulin-dependent DM
 adult-onset diabetes
Classification of DM

4. 

5. 

6. 

7. 
 Insulin Resistance
 Abdominal obesity
 Men waist circumference greater than 102cm (40
inches)
 Women waist circumference greater than 88cm (35
inches)
 Triglycerides greater than 150 mg/dL (1.70 mmol/L)
 HDL cholesterol
 Men less than 40 mg/dL (1.04 mmol/L)
 Women less than 50 mg/dL (1.3 mmol/L
Etiology (for type II)

8. 
Risk Factors (for type II)

9.  Glucose intolerance occurring during pregnancy
Gestational diabetes

10. 
 Immunosuppressant (decrease insulin synthesis)
 Corticosteroids, ACTH, GH and combined oral contraceptives
(increase gluconeogenesis & lipolysis or increase tissue
resistance to insulin)
Factors inducing DM

11. 
Type-1 and Type-2 DM diagnosis (non-pregnant)
 Fasting plasma glucose (FPG)
Easy and preferred method
≥ 110 mg/dL
 Random plasma glucose
≥ 180 mg/dL with symptoms of hyperglycemia
(polyuria, polydepsia, and unexplained weight loss)
Prudent to obtain HbA1c level as well
 Oral glucose tolerance test (OGTT)
Plasma glucose concentration obtained at time intervals of 30 min. after a
75g oral glucose ingestion ≥ 200 mg/dL
More sensitive and specific than FBG
 HbA1c (Glycated hemoglobin)
-6.5% or greater
-Confirmed by repeating
-Does not require fasting
Diagnosis

12. 
Other diagnostic tests differentiate between type 1 and type 2 DM
C -peptide (measure of insulin secretion)
-Negligible in type-1 DM and
-Normal or elevated in type-2 DM
-used for differentiation between type 1 and type 2
Islet cell autoantibodies, autoantibodies to insulin
(suggest autoimmune activity)

13. 
More common in
DM type 1

14. 
Complications of Diabetes

15. 
Prevent acute or chronic complications
 Acute complications.
 Hyperglycemia, Diabetic ketoacidosis (DKA).
 Chronic complications (Micro and Macro)
Glycemic goals of therapy
 HbA1c < 7.0%
 Fasting plasma glucose 70-130 mg/dL
 Peak postprandial glucose (1-2 hours after meal) <180 mg/dL
Non-glycemic goals of therapy
 Blood pressure < 130/80 mm Hg
 LDL-C < 100 mg/dL
 TG < 150 mg/dL
Management Goal

16. 
Goals of gestational diabetes management
Prevent complications in mother or child:
- Mother: type-2 DM after pregnancy, hypertension,
preeclampsia.
Glycemic goals of therapy (more stringent)
- Fasting plasma glucose 95 mg/dL or less
- 1-hour postprandial glucose 140 mg/dL or less
- 2-hour postprandial glucose 120 mg/dL or less
Management Goal

17. 
Treatment
1. Diet (caloric restriction in obese patients)
2. Oral hypoglycemic drugs
3. Insulin :
- Alone (in type 1 DM or in Gestational Diabetes)
- Or in combination with oral hypoglycemic drug
(in type 2 DM)

18. 
A- Sulphonylureas
B- Glinids (meglitinides)
C- Biguanides (metformin)
D- Thiazolidinediones (Glitazones)
E- Alpha - glucosidase inhibitors
F- Dipeptidyl peptidase-4 inhibitors (Gliptins)
G- Sodium–glucose cotransporter 2 inhibitors
Oral Hypoglycemic Drugs

19.  GLP-1
(incretin)
Target Cell
Polysach. 
Starch
Oligo
Glucose
α -
glucosidase
insulin
K+
Ca++
↓ Glucagon, ↓ GER, ↑ Satiety
Inactive cpd
Amylin
DPP IV
↑ insulin ↓ Glucagon,
↓ GER, ↑ Satiety

20. 
Sulphonyl Urea
(Drug Inter. Effect)
Meglitinide
Repaglinide
Nateglinide
(Rapid & short
acting)
↑Insulin release,
↑ risk of
hypoglycemia
& weight gain
GLP-1
(incretin)Target Cell
Polysach. 
Starch
Oligo
Glucose
α-glucosidase
inhibitor
Acarbose
↓ pancreatic α
Amylase & α
Glucoside 
↓ Glucose
Absorption
α -
glucosidase
GLP-1 Analogue
(Incretin mimetic)
Exenatide
Liraglutide
DPP IV inh.
Sitagliptin
Saxagliptin
↓ breakdown of
GLP-1
Amylin
Analogue
Pramlinitide
(SC. injection)
All ↑Insulin Secretion, ↓ Glucagon,
↓ GER, ↑ Satiety
insulin
Biguanides
(Metformin)
TZD
(Pioglizone)
Just ↑ action of
normal insulin.
No
hypoglycemia &
no weight gain.
K+
Ca++
Dulaglutide
Once per week
Inactive cpd
DPP IV
Amylin

21. Sodium–glucose cotransporter 2 inhibitors
The SGLT2 is responsible for reabsorbing filtered glucose in the
tubular lumen of the kidney. By inhibiting SGLT2, these agents:
- Decrease reabsorption of glucose,
- Increase urinary glucose excretion,
- And lower blood glucose

22. 
 Classification of sulphonylureas:
 Second generation:
 Third generation:
 N.B First-generation agents are rarely used today
A- Sulphonylureas
Gliclazide
Glibenclamide
Glimepiride

23. 
S.Es
 Hypoglycemia in high doses
 increased appetite and weight gain
 Nausea, vomiting, allergic reactions, headache
 Confusion, ataxia, drowsiness
 Teratogenicity**
Sulphonylureas

24. 
Interactions:
Sulphonylureas
Drugs Reducing the effects
of SU leading to loss of
glucose control:
• Corticosteroids
• Diuretics
• Sympathomimetics
• oral contraceptives
Drugs potentiate the
effects of SU leading to
hypoglycemia:
• Beta-blockers
• Chloramphenicol
• Clarithromycin
• Salicylates
• sulfonamides

25. 
 Increase insulin release by blocking ATP K channels
 Decrease risk of hypoglycemia
 Rapid acting and very short acting
 Effective against the release of insulin after meals
(postprandial glucose regulators).
 Adverse effects: weight gain, upper respiratory
infection
B- Glinides (Meglitinides)
Repaglinide - Nateglinide

26. 
 Metabolized to inactive products by CYP3A4 in the
liver and execreted through the bile, so
contraindicated in liver disease and have some drug
interactions.
 Interactions:
Drugs that induce
CYP3A4 decrease
repaglinide effect:
• Barbiturates
• Carbamazepine
• Rifampin
Drugs that inhibit
CYP3A4 increase
repaglinide effect:
• Fluconazole
• Erythromycin
• Clarythromycin

27. Mechanism of action:
 increase Glycolysis (peripheral tissues)
 Decrease Gluconeogenesis (liver)
 Slowing glucose absorption from gut
 Decrease Glucagon level
 increase Insulin binding to its receptor( decrease insulin resistance)
Adverse Effects:
 Nausea, diarrhea, loss of appetite, metallic taste
Contraindications:
 Renal diseases
 Pulmonary disease
 Cardiac diseases
Interaction:
Long term use may interfere with vitamin B12 absorption
C- Biguanides(Metformin)

28. 
Rosiglitazone - Pioglitazone
Mechanism of action
 Increases expression of genes responsible for glucose
metabolism, resulting in improved insulin sensitivity
Adverse Effects
 Weight gain,
 Risk of bone fractures,
 Fluid retention
 Increased risk of heart failure,
myocardial infarction
and cardiovascular death
D- Thiazolidinediones
(glitazones)

29. 
Acrabose
Mechanism of action
 Slows the absorption of glucose from the intestine
into the bloodstream by slowing the breakdown of
large carbohydrates into smaller absorbable sugars
Adverse Effects
 Flatulence, diarrhea
 Increased levels of liver enzymes levels observed
with high doses of Acarbose
E- Alpha glucosidase inhibitor

30. 
Sitagliptin, Saxagliptin
Mechanism of action
 Inhibits the breakdown of glucagon-like peptide-1 (GLP-
1) secreted during meals, which in turn:
 increases pancreatic insulin secretion
 limits glucagon secretion
 slows gastric emptying
 promotes satiety
Adverse Effects
 Upper respiratory and urinary tract infections, headache
F- Dipeptidyl-peptidase-4 inhibitors
(Gliptins)

31. Canagliflozin - Dapagliflozin - Empagliflozin
G- Sodium–glucose cotransporter 2
inhibitors
Mechanism of action
The SGLT2 is responsible for
reabsorbing filtered glucose in the
tubular lumen of the kidney. By
inhibiting SGLT2, these agents:
- Decrease reabsorption of glucose,
- Increase urinary glucose excretion,
- And lower blood glucose

32. Adverse effects:
 The most common adverse effects with SGLT2 inhibitors
are female genital mycotic infections (for example
candidiasis), urinary tract infections, and urinary
frequency.
 Hypotension has also occurred, particularly in the elderly
or patients on diuretics

33. 

34. 
Pramlinitide
- Sc injection
- Increase Insulin Secretion,
decrease Glucagon secretion ,
decrease GER, and increase Satiety
Amylin analogue

35. 
When does it necessary to use insulin?
 Type I DM
 In Type II DM if:
 HbA1c > 10
 Or Random glucose > 300 mg/dL or fasting glucose > 250
mg/dL
 Or Presence of urine ketones
Insulin

36. 
 Insulin is categorized on the basis of duration of
therapy after injection
Insulin

37. 

38. 
Dosage and Administration
 Insulin is not effective if given orally (destroyed by
proteolytic enzymes of GIT)
 All insulin preparations are given S/C.
 Soluble insulin (Regular insulin) can be given
intravenously in emergency cases.
(Dosage is measured in international units standardized by
chemical assay.)
Iinsulin pump (Continuous subcutaneous insulin infusion)
Device allows very patient-specific hourly basal dosing and
bolus insulin dosing (use rapid-acting insulins).
https://www.youtube.com/watch?v=t7ajHnpaLpk

39. 
Local adverse effects
 Allergy, secondary infection, atrophy or hypertrophy
of S/C fat
Systemic adverse effects
 Hypersensitivity reaction
 Hypoglycemia, hypoglycemic coma (due to excess
insulin, little food or excessive muscular exercise
Insulin S.Es

40. 
 Rapid hypoglycemia: sweating, tachycardia, tremors
 Slow hypoglycemia: headache, blurred vision,
diplopia, mental confusion, convulsions, coma
**Treatment
 If conscious: glucose, oral sweets
 If comatosed: 50% glucose I.V., adrenaline S/C,
glucagon I.M. or S/C
Hypoglycemia

41. 
A 40 year old previously healthy man presents to the
emergency room with a 2-week history of polyuria, polydipsia
and a 20-lb unintentional weight loss. He complains of
weakness, fatigue, nausea and abdominal pain. Physical
examination reveals dry, parched mucous membranes, blood
pressure is 110/70 mmHg and the pulse is 90 beats per minute
(bpm) supine. Respiratory rate is 30 breaths /min. Lab
diagnosis revealed ketoacidosis.
Case 1

42. 
Normal ValuePatient valueParameter
Less than 110 mg/dl420 mg/dlFasting Blood glucose
136-145 mmol/L130 mmol/lsodium
3.5-5.0 mmol/L3.7 mmol/lpotassium
mmol/l95-10597 mmol/lChloride
23-30 mmol/L10 mmol/lbicarbonate
37 ºC39 ºCtemperature
Lab analysis:

43. 
 A- Type 2 DM without hyperosmolar state.
 B- Type 2 DM with diabetic ketoacidosis.
 C- Type 1 DM without diabetic ketoacidosis.
 D- Type 1 DM without hyperosmolar state.
1) What is the most likely diagnosis
in this patient? rationalize your answer.
Type 2 >>> age (40 years)
DKA >>> ↓ bicarbonates (so acidosis)

44. 
 A. Control serum glucose as tightly as possible
 B. Control triglyceride biosynthesis
 C. Maintain adequate hepatic glycogen stores
 D. Maintain serum K+ homeostasis
2) Which of the following is the goal of
insulin therapy?

45. 
 a- Urine monitoring.
 b- Blood monitoring.
 c- Renal function monitoring.
 d- Cardiovascular monitoring.
3) The most useful glucose test used
in monitoring DM therapy is:

46. 
 Family history
 Lack of exercise
 Unhealthy diet
 Obesity
4) Enumerate the risk factors for
diabetes?

47. 
 If glycated haemoglobin HbA1c > 10.
 If Random glucose > 300 mg/dL or fasting glucose > 250
mg/dL.
 If ketone bodies were found in urine.
5) When does it necessary to use
insulin?

48. 
 Hypoglycemia
6) If we use sulphonylureas in
treatment of type 2 DM. What is the
most common side effect ?

49. 
Because oral contraceptives reduce the effects of
sulphonylureas leading to loss of glucose control as they
increase gluconeogenesis.
7) Rationalize, Oral contraceptives used
cautiously when given with
sulphonylureas during treatment of DM?

50. 
 Renal diseases
 Pulmonary diseases
 Cardiac diseases
8) Biguanides are contraindicated in
many diseases. Enumerate.

51. 
9) What is the etiology of DM?
 Insulin Resistance
 Abdominal Obesity
Men waist circumference greater than 102 cm (40 inches)
Women waist circumference greater than 88 cm (35 inches)
 Triglycerides greater than 150 mg/dL (1.70 mmol/L)
 Decrease level of HDL cholesterol
Men less than 40 mg/dL (1.04 mmol/L)
Women less than 50 mg/dL (1.3 mmol/L

52. 
 Sulfonylureas
 Meglitinides
 Dipeptidyl peptidase-4 inhibitors
 GLP-1 analogs
 Amylin analogue
10) Enumerate different drug classes
which increase insulin level?

53. A.B. is a retired 69-year-old man with a 5-year history of type 2 diabetes.
Although he was diagnosed in 2013, he had symptoms indicating
hyperglycemia for 2 years before diagnosis.
1- Why this is not a type 1 diabetes?
Age (69 year)
2- What are the symptoms that indicate hyperglycemia?
Polyuria, polydipsia
Case 2

54. A.B. states that he has “never been sick a day in my life.” He recently sold his
business and has become very active in a variety of volunteer organizations.
He lives with his wife of 48 years and has two married children. Although both
his mother and father had type 2 diabetes, A.B. has limited knowledge
regarding diabetes self-care management and states that he does not
understand why he has diabetes since he never eats sugar.
3- What is the importance of the past information?
That type 2 diabetes is a genetic disease and since his parents both are
diabetic, A.B. should have paid much attention to his health.

55. He had fasting blood glucose records indicating values of 118–127 mg/dl,
which were described to him as indicative of “borderline diabetes.” He also
remembered past episodes of nocturia associated with large pasta meals
and Italian pastries. Referred by his family physician to the diabetes specialty
clinic, A.B. presents with recent weight gain, suboptimal diabetes control,
and foot pain. At the time of initial diagnosis, he was advised to lose weight
(“at least 10 lb (5 kg).”). He has been trying to lose weight and increase his
exercise for the past 6 months without success.
4- Why was he advised to lose weight?
This is a non-pharmacological treatment for patients with diabetes Type
2, as losing weight improves insulin sensitivity.

56. He had been started on glyburide (Diabeta), 2.5 mg every morning.
5- To which class does this drug belong? What is the MAIN
mechanism of action? What are the common side effects of this
class?
- Sulfonylureas
- Insulin secretagogue (may also ↑ peripheral insulin sensitivity, ↓
hepatic gluconeogenesis)
- Hypoglycemia/hyperinsulinemia that can be accompanied with
dizziness, sweating, and agitation.

57. A.B has tolerated this medication and adheres to the daily schedule. He does
not test his blood glucose levels at home and expresses doubt that this
procedure would help him improve his diabetes control. “What would knowing
the numbers do for me?,” he asks. “The doctor already knows the sugars are
high.”
6- What is the advice for diabetic patients to control their situation?
To have a device to measure the blood glucose level at home.
A.B had stopped taking his drug because of dizziness, often accompanied by
sweating and a feeling of mild agitation, in the late afternoon.
A.B. also takes atorvastatin (Lipitor), 10 mg daily
7- What is the indication of this drug?
For hypercholesterolemia (elevated LDL cholesterol, low HDL cholesterol,
and elevated triglycerides).

58. A.B.’s diet history reveals excessive carbohydrate intake and limited
physical activity.
The medical documents that A.B. brings to this appointment indicate that his
hemoglobin A1c(A1C) has never been <8%.
8- What does this value indicate?
His glucose is very high for long period that it glycated Hb, the required
value is to have A1C below 7%.
A.B. has never had a foot exam as part of his primary care exams, nor
has he been instructed in preventive foot care.
9- What is the indication of this sentence?
Diabetes is known to cause neuropathy as a complication that affects
the sensation in the periphery, mostly the foot.

59. Physical Exam
A physical examination reveals the following:
 Weight: 178 lb (178/2.2=82 Kg); height: 5′2″; body mass index (BMI): 32.6 kg/m2
 Fasting capillary glucose: 166 mg/dl
 Blood pressure: lying, right arm 154/96 mmHg; sitting, right arm 140/90 mmHg
 Pulse: 88 bpm; respirations 20 per minute
 Eyes: corrective lenses, pupils equal and reactive to light and accommodation,
Fundi-clear, no arteriolovenous nicking, no retinopathy
 Thyroid: nonpalpable
 Lungs: clear to auscultation
 Heart: Rate and rhythm regular, no murmurs or gallops
 Vascular assessment: no carotid bruits; femoral, popliteal, and dorsalis pedis
pulses 2+ bilaterally
 Neurological assessment: diminished vibratory sense to the forefoot, absent
ankle reflexes, monofilament (5.07 Semmes-Weinstein) felt only above the
ankle

60. Lab Results
Results of laboratory tests (drawn 5 days before the office visit) are as follows:
 Glucose (fasting): 178 mg/dl (normal range: 65–109 mg/dl)
 Creatinine: 1.0 mg/dl (normal range: 0.5–1.4 mg/dl)
 Blood urea nitrogen: 18 mg/dl (normal range: 7–30 mg/dl)
 Sodium: 141 mg/dl (normal range: 135–146 mg/dl)
 Potassium: 4.3 mg/dl (normal range: 3.5–5.3 mg/dl)
 Lipid panel
• Total cholesterol: 162 mg/dl (normal: <200 mg/dl)
• HDL cholesterol: 43 mg/dl (normal: ≥40 mg/dl)
• LDL cholesterol (calculated): 84 mg/dl (normal: <100 mg/dl)
• Triglycerides: 177 mg/dl (normal: <150 mg/dl)
• Cholesterol-to-HDL ratio: 3.8 (normal: <5.0)
 AST: 14 IU/l (normal: 0–40 IU/l)
 ALT: 19 IU/l (normal: 5–40 IU/l)
 Alkaline phosphotase: 56 IU/l (normal: 35–125 IU/l)
 A1C: 8.1% (normal: 4–6%)
 Urine microalbumin: 45 mg (normal: <30 mg)

61. 10. What do these values indicate?
The patient has dyslipidemia controlled by atorvastatin, hyperglycemia,
peripheral neuropathy and an initial change in the kidney function (high
urine microalbumin) although creatinine and BUN are within the normal
range. This marker is indicator of probability of decreased glomerular
capacity to filtrate blood and it is used for early diagnosis of diabetic
nephropathy.

62. 11. What is the assessment for A.B case depending on his medical history,
records, physical exam, and lab results?
A.B is assessed as follows:
- Uncontrolled type 2 diabetes (A1C >7%)
- Obesity (BMI 32.4 kg/m2)
- Hyperlipidemia (controlled with atorvastatin)
- Peripheral neuropathy (distal and symmetrical by exam)
- Hypertension (by previous chart data and exam)
- Elevated urine microalbumin level
- Self-care management/lifestyle deficits
- Limited exercise
- High carbohydrate intake
- No SMBG program (self-monitoring blood glucose)
- Poor understanding of diabetes

63. 