این فایل جهت یادگیری بهتر دانشجویان پزشکی فراهم شده است. دکتر هاله چهره گشا فوق تخصص غدد و عضو هیات علمی دانشگاه ایران بیمارستان حضرت رسول اکرم تهران chehrehgosha.h@iums.ac.ir

1. In the name of God

2. Basic principles
Diagnosis and classification
Management
2
Agenda

3. Management

4. 25. Why do some patients with prediabetes/early diabetes present with postprandial hypoglycemia?
4

5. How to manage?
A 44-year-old obese male, was incidentally detected
to have T2DM with fasting blood glucose 150 mg/dl
and HbA1c 8%. He had no diabetes related
complications. He insists on avoiding medications.
“
Case 1

6. Answer, case 1
6

7. 26. What is the use of artificial sweeteners in the management of diabetes?
7

8. 27. Can exercise improve insulin sensitivity without weight loss?
8

9. 28. How to advice a patient with T2DM regarding exercise?
9

10. 29. Why is metformin considered as the first-line drug for the management of patients with T2DM?
10

11. 30. Mechanism of action
11

12. 31. Why metformin therapy is not associated with increased risk of hypoglycemia?
12

13. Should metformin be
discontinued?
A 44-year-old obese male with type 2 diabetes for 5
years is on therapy with metformin 500 mg twice a
day, with fasting blood glucose 100 mg/dl, HbA1c
7.1% and serum creatinine of 1.6 mg/dl.
“
Case 2

14. Answer, case 2
14

15. What to do next?
A 62-year-old postmenopausal female with type 2
diabetes for 3 years, is on therapy with metformin 2
g/day, has HbA1c of 7.8%. She is skeptical of using
sulfonylureas because of a previous hypoglycemic
event.
“
Case 3

16. Answer, case 3
16

17. What to do next?
A 58-year-old male with T2DM for 3 years, is on
therapy with metformin 2 g/day, has HbA1c of 8.7%.
He has congestive heart failure and is fearful of
insulin.
Case 4
“

18. Answer, case 4
18

19. Drug class
19

20. 20

21. 21
https://pharmadoodles.com

22. 32. What is the dosing schedule and time of administration of sulfonylureas?
22

23. 33. What should be the time of administration of antidiabetic drugs?
23

24. 34. What is the HbA1c-reducing efficacy of various treatment modalities in the management of diabetes?
24

25. What are the probabilities?
A 58-year-old male well controlled (HbA1c 7.1%) with
metformin, sulfonylurea, and pioglitazone presented
with a history of sudden worsening of vision.
Case 5
“

26. Answer, case 5
26

27. 35. Is the risk for bladder cancer with pioglitazone real?
27

28. 36. What are the differences between GLP1 agonist and DPP4 inhibitors?
28

29. 37. How is the insulin secretion stimulated by DPP4 inhibitors different from sulfonylureas?
29

30. 38. Why is therapy with DPP4 inhibitors/GLP1 analogues associated with low risk of hypoglycemia in
patients with T2DM?
30

31. 39. What are the nondiabetic benefits of GLP1 analogues?
31

32. 40. Is there a risk of pancreatitis with incretin-based therapy?
Suspected
pancreatitis
Not
stablished
reported
Clinical
trials
Causality
Discontinue
32

33. 41. Is there a risk of tumors with incretin therapy?
Liraglutide
rodents
Thyroid C-cell
tumors
Human
Relevance not
determined
33

34. 42. What is the rationale of combining GLP1 agonists and basal insulin?
34

35. 43. What are SGLT2 inhibitors?
if eGFR is <45 ml/min or if
baseline HbA1c is <7.7%
SGLT2i
suppresses 30–40%
loss of 300 Kcal
(~75 g glucose)
per day
35

36. 44. What are the characteristics of SGLT2 inhibitors?
36

37. 45. What are the unique features of insulin glargine?
“peakless”
long-acting
acidic pH of 4
Micro
precipitates
in
subcutaneous
tissue
Cannot be
mixed with
other insulins
duration of
action 18–24
h
10% of
patients
require twice
daily
usually basal
insulin during
night
37

38. 46. What are the concerns with the use of insulin glargine?
insulin glargine is converted into metabolites,
which has much lesser affinity for IGF1 receptor
as compared to human insulin
not supported
by most
meta-analysis
and ORIGIN
study
supported
by in vitro
data
Many
observational
studies:
increased risk
of cancer
this risk has been
refuted
progression
of diabetic
retinopathy
38

39. 47. Which insulin is weight neutral?
39

40. 48. What are the characteristics of insulin detemir?
40

41. 49. How does insulin degludec differ from glargine?
41

42. 50. What is the utility of premixed insulin in the management of T2DM?
42

43. 51. When to initiate insulin in patients with type 2 diabetes at diagnosis?
HbA1c >9%
osmotic
symptoms
significant
weight loss
fasting
plasma
glucose
>200–250
mg/dl
ketosis/ket
oacidosis
Complication
(infections,
ACS,
significant
hepatic-renal
dysfunction)
43

44. 52. What is Monnier’s hypothesis?
HbA1C
>10.2%
HbA1C
7.3-10.2%
HbA1C
<7.3%
70% by post-
prandial
fasting = post-
prandial
70% by fasting
44

45. 53. What should be targeted first in a patient with diabetes who have both fasting and postprandial
hyperglycemia?
Fasting Postprandial
45

46. What to do next?
A 52-year-old man with type 2 DM of 8 year duration
had FPG 170 mg/dl and HbA1c 8.9%. He is on
metformin 2 g per day and glibenclamide 2 mg per
day.
Case 6
“

47. Answer, case 6
further increase in doses of
sulfonylurea or metformin has only
modest effects on glycemia
The addition of DPP4 inhibitors, SGLT2
inhibitors or α-glucosidase inhibitors
will decrease HbA1c only by 0.5–0.8%
Addition of pioglitazone may not help
to achieve target HbA1c in this
individual
addition of basal insulin, or long acting
GLP-1 agonist
Best option
47

48. 54. When to add basal insulin?
It is ideal to add basal insulin as early as possible because T2DM is also an
insulin-deficient state.
Various studies have demonstrated that use of insulin in newly diagnosed
T2DM even for 2–4 weeks resulted in early attainment of target HbA1c, stable
glycemic control, and preservation of β-cell function over the next few years.
In clinical practice, basal insulin is added either in second tier or third tier to
control fasting hyperglycemia, especially if HbA1c is >8.5%.
48

49. 55. Who are the candidates for self-monitoring of blood glucose?
Candidates
All T1DM or
T2DM on
intensive insulin
therapy
Type 2 diabetes
on less intensive
insulin therapy
All gestational
diabetes
49

50. What to do next?
A 57-year-old man was referred for glycemic
management. He was diagnosed with type-2 diabetes
3 months prior by his primary care physician. HbA1
level of 9.7 % with a fasting plasma glucose of 258
mg/dL.
Case 7
“
• Polyurea and polydipsia
• Weight loss
• Metformin ER 500 mg once daily
• loose stools and bloating
• Denies hypoglycemia
• Body Mass Index 33.4 kg/m2
• Creatinine 1.0 mg/dL

51. 56. What Are Appropriate Glycemic Goals for This Patient?
51

52. Goals in diabetes
52

53. What Are the Various Treatment Options for Newly Diagnosed Patients with Type-2 Diabetes?
53

54. If HbA1c above goal
54

55. • Past medical history: nephrolithiasis and cholecystectomy 8
years ago.
• Family history: mother diagnosed with type-2 diabetes, his
father had coronary artery disease at age 53.
• He denies any history of tobacco or alcohol use. Current
medications: aspirin 81 mg daily, hydrochlorothiazide 25
mg daily, metformin ER 500 mg once daily.
Case 7 …
“
Creatinine 1.0 mg/dL
LDL 126 mg/dL
Triglycerides 209 mg/dL
HDL 37 mg/dL

56. 57. Should This Patient Be Screened for Cardiovascular Disease?
Abnormal renal function
Abnormal resting ECG
Abnormal fundoscopic examination
Cardiac symptoms
Family history of premature coronary disease
Modifiable risk factors such as elevated LDL cholesterol and obesity
56

57. 58. Should This Patient with an LDL Cholesterol of 126 mg/dL Be Treated?
57

58. 59. Should We Continue This Patient’s Low Dose Aspirin Therapy?
58

59. 60. What Are the Target Blood Pressure Goals for This Patient with Newly Diagnosed Type-2 DM?
59

60. 61. What Initial Clinical and Laboratory Evaluation Is Recommended
for This Patient with Newly Diagnosed Type-2 Diabetes?
60

61. • A 65-year-old woman was diagnosed with diabetes 8 years prior to
her presentation by routine blood work. She was initially started
on metformin 500 mg twice daily at the time of diagnosis.
Metformin dose was increased to 1,000 mg twice daily 3 years
after diagnosis.
• She had experienced good glycemic control until 1 year ago. HbA1c
level was 6.8 % 1 year prior to this visit. The patient was feeling
well. She denied polyuria, polydipsia, visual changes, or
hypoglycemia or distal paresthesias.
Case 8
“
Fasting blood glucose
levels ranged from 170
to 190 mg/dL
BMI 28.9 kg/m2

62. What to do next?
Sulfonylurea
DPP4i
GLP-1 RA
SGLT2i
Meglitinide
Insulin
62

63. 62. Oral antidiabetic agents?
Generic
name
Dosage forms Starting
dose
Maximum
dose
Metformin 500, 1000 mg 500 mg qd 2000 mg qd
Gliclazide Modified release 30, 60 mg
Immediate release 80 mg
30 mg qd
80 mg BD
120 mg qd
320 mg/day
Repaglinide 0.5, 1, 2 mg 0.5 mg TDS 4 mg TDS
Sitagliptin 25, 50, 100 mg 100 mg qd 100 mg qd
Linagliptin 5 mg 5 mg qd 5 mg qd
Liraglutide 6 mg/ml 0.6 mg qd 1.8 mg qd
Empagliflozin 10, 25 mg qd qd
Pioglitazone 15, 30, 45 mg 15 mg qd 45 mg qd 63

64. 64
Which is better for this patient?
Interaction
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65. 63. When to Consider Transitioning to Insulin Therapy?
The United Kingdom Prospective
Diabetes Survey (UKPDS)
gradual worsening of glycemic
control in type-2 diabetes
result of progressive loss of
insulin producing pancreatic beta
cells
need for insulin therapy after a
diabetes duration of 10–15 years
is common
65

66. 64. When insulin should be started in T2DM?
66

67. 65. How to start insulin in T2DM?
67

68. 66. Are patients on basal insulin attaining glycemic targets?
68

69. 67. Insulin formulations?
69

70. Types of insulin regimens
70
Insulin pump Multiple insulin injection
regimen
NPH/regular regimen

71. 69. Comparing long-acting analogue insulins over NPH insulin?
NPH insulin
Long-acting analogue
insulins
Nocturnal
hypoglycaemia
71

72. 70. Premixed insulin?
① once daily
dose
10 U/day once daily
or 0.3-0.5 U/kg/day
TDD < 20 U
② Twice a day if TDD >20 U
titrate once or twice
weekly
Premixed
insulin
72

73. 71. Premix human insulin vs. Premix analogue insulin?
73

74. 72. Regular insulin vs. rapid-acting insulins?
The use of
regular insulin
generally discouraged
less physiologic
pharmacokinetic profile
slower absorption
longer duration of
action
inadequate prandial
coverage
late postprandial
hypoglycemia
74

75. 73. Comparing the effects of basal insulins alone versus premixed
insulin injections twice daily?
75

76. 74. How to calculate the insulin-to-carbohydrate ratio
The 500 rule
dividing 500 by
the total daily
insulin dose
grams of carbohydrate
covered by 1 unit of
rapid-acting insulin
76

77. What are the probabilities?
A 30-year-old woman with chief complaint of a “recurrent yeast
infection.” Over the last several years, she has gained more than
10 Kg. She had excessive weight gain in pregnancy and her baby
had to be delivered by cesarean because he weighed 4500 g.
Family history is unknown. BMI = 31.6. Blood pressure is 140/90.
Vaginal candidiasis was detected.
Case 9
“

78. Question 1 and answer, case 9
Q1: What is the most
likely primary
diagnosis for this
patient?
A1: IFG or T2DM
(fetal macrosomia,
GDM or
unrecognized T2DM)
Q2. What physical
findings are
suggestive of this
diagnosis?
A2: Obesity,
acanthosis nigricans,
hypertension,
candidal vaginitis
78

79. A 45-year-old man with diabetes since one years ago and 8-
week history of progressive polyuria, polydipsia, fatigue, blurred
vision, and an 4 kg weight loss. He was on metformin and
sulfonylurea with BS 140 mg/dl by another physician. No FH of
DM. BMI, 22.7, FPG 320 mg/dL, bicarbonate 14 mEq/L, LDL 82
mg/dL, HDL 60 mg/dL, and TG 56 mg/dL, serum ketone +
Case 10

80. Question 1 and answer, case 10
Q1. What type of DM
does the patient have?
Type 1: Weight loss, lean body habitus,
lack of FH of DM, lack of HTN, and
dyslipidemia
Type 2: Older age, more common overall,
lack of ketoacidosis
80

81. Question 2 and answer, case 10
Q2. What is the final
diagnosis?
A2. Patient had positive anti-GAD
antibodies. LADA = latent autoimmune
diabetes in adults (T1.5DM).
81

82. An 8-year-old girl had hyperglycemia (715 mg/dL) and marked
growth retardation (birth weight – 1650 g). She has been treated
with insulin since birth. Diabetes-related antibodies have been
undetectable on several occasions. Basal serum c-peptide
concentrations were low at birth, declined further with age, and did
not increase in response to glucagon. The girl has no evidence of
diabetic complications. Her mother has IFG, and her father has IGT
but neither parent is obese.
Case 11

83. Question 1 and answer, case 11
Q1. What type of DM
does the patient have?
The patient is young and thin which
favors T1DM. However, she has no
evidence of autoimmunity and no
reported episodes of DKA which favors
T2DM.
Next look at the family for evidence of
T2DM. Both the mother and father have
prediabetes, but neither is obese. This
makes you wonder about T2DM.
83

84. Question 2 and answer, case 11
Q2. What tests could help distinguish between T1DM and T2DM?
You might consider remeasuring autoantibodies if the panel was
incomplete.
C-peptide measurements are less helpful at diagnosis because c-peptide
can be low in both new-onset T1DM and new-onset, uncontrolled T2DM.
We are told that c-peptide measurements have declined over time so
remeasuring them now is probably unnecessary.
84

85. Question 3 and answer, case 11
Q3. What is the most likely diagnosis?
Most likely Dx is MODY. In this case you should send DNA for sequencing to determine the exact
cause.
MODY is a monogenic diabetes caused by mutations in the glucokinase enzyme gene or
hepatocyte/ islet transcription factors.
In the former case (MODY2), higher glucose levels are required to elicit insulin secretory responses,
thus altering the set point for insulin secretion.
In the latter case, several forms of MODY may be due to abnormal development of pancreatic β-
cells.
85

86. Question 4 and answer, case 11
Q4. What tests could help distinguish between T1DM and T2DM?
Most patients with MODY are treated with sulfonylurea drugs
because it is principally a genetic problem in the pancreatic beta-
cell.
These agents are more or less effective depending on the exact
cause of the disorder.
86

87. 68. The causes of secondary drug failure to Oral hypoglycemic
agents?
87

88. References
88