Diabetes Mellitus

2. BY
Dr. HUSSEIN SAAD, MRCP (UK)
Assistant Professor
Consultant Family Medicine
College of Medicine
King Saud University
DIABETES MELLITUS

3. Genetic predisposition
IGT
Insulin Resistance
(Hyperinsulinemia)  Cell
Defect
Usually 50% of  cells are
functioning at time of
diagnosis
Type 2 Diabetes

4. CLASSIFICATION
 Type 1 diabetes (absolute insulin deficiency)
 Type 2 diabetes (insulin resistance with relative insulin
def.)
 Gestational diabetes mellitus
 Other types (genetic or secondary types)

5. Prevalence of DM in Saudi Arabia

A community based study of 17232 subjects
conducted between 1995 and 2000 in KSA.
 The examining age group, 30-70 years of selected
households during 5-year period
Mansour M. Al-Nozha et al,The prevalence of CAD among Saudis of both sexes, in rural as
well as urban communities, as well as modifiable risk factors for CAD.
Saudi Medical Journal 2004; Vol. 25 (9): 1165-1171

6. Prevalence of DM in Saudi Arabia
 The overall prevalence of DM obtained from this
study is 23.7% in KSA.
 The prevalence in males and females were
26.2% and 21.5% respectively (p<0.00001).
 A large number of diabetics 1116 (27.9%) were
unaware of having DM.
Mansour M. Al-Nozha et al,The prevalence of CAD among Saudis of both sexes, in
rural as well as urban communities, as well as modifiable risk factors for CAD.
Saudi Medical Journal 2004; Vol. 25 (9): 1165-1171

7. Current DIAGNOSIS
 Symptomatic patient plus casual plasma glucose
≥ 11.1 mmol/L or FPG ≥ 7.0 mmol/L.
 During an OGTT 2-hr post 75 gm-glucose ≥ 11.1
mmol/L.
 In the absence of symptoms suggestive of DM, these
criteria should be confirmed by repeat testing on a
different day.
 HbA1C ≥ 6.5% DIABETES CARE, VOLUME 33, SUPPLEMENT
1, JANUARY 2014.

8. DIAGNOSIS
 FPG ≤ 5.5 mmol/L = normal
 FPG ≥ 5.6 mmol/L to 6.9 mmol/L= IFG
 FPG ≥ 7.0 mmol/L = provisional diagnosis of DM and
must be confirmed in asymptomatic person.
 HbA1C ≥ 6.5%
 If two different tests (such as A1C and FPG) are both
above the diagnostic thresholds the diagnosis of diabetes
is confirmed.

9. Screening FOR DM IN ASYMPTOMATIC
 All individuals at age 45 years or above.
 At younger age or more frequently in whom:
■ Are Obese
■ Have a first degree relative with diabetes
■ Are Hypertensive ≥ 140/90
■ Have been diagnosed with GDM
■ Have Dyslipidaemia
■ Had IGT or IFG or HbA1C ≥ 5.7
■ Women with polycystic ovarian syndrome (POS)
Women with polycystic ovarian syndrome (PCOS)
≥

10. Diagnosis based on: Glucose Tolerance Test
2 hr post 75 gm glucose
 If < 7.8 mmol/L = normal GTT
 If ≥ 7.8 mmol/L and < 11.1 mmol/L = Impaired GTT
 If ≥ 11.1 mmol/L = provisional diagnosis of
Diabetes

11. Prediabetes
Persons with an A1C of 5.7–6.4%, IGT, or IFG should
be counseled on lifestyle changes.
Three large studies of lifestyle intervention has shown
sustained reduction in the rate of conversion to type 2
diabetes,
 43% reduction at 20 years in the Da Qing study.
 43% reduction at 7 years in the Finnish Diabetes
Prevention Study (FDPS).
 34% reduction at 10 years in the U.S. Diabetes
Prevention Program Study (DPPS) .
 A consensus panel felt that Metformin should be the
choice of drug considered .

12. When to add Metformin in pre-diabetes?
 In addition to lifestyle counseling, Metformin is
considered in IFG plus:
Hypertension,
Low HDL cholesterol,
Elevated triglycerides,
Family history of diabetes (first-degree relative),
Obese,
Under 60 years of age.
DIABETES CARE, JANUARY 2012.

14. Optimal Treatment of Type 2 Diabetes means treating
Hyperglycaemia and the Dysmetabolic Syndrome
NEED TO
TREAT
Good glycaemic control
Microvascular
& Macrovascular
Complications
Insulin resistance, obesity,
hyperinsulinaemia, hypertension,
dyslipidaemia, atherosclerosis,
procoagulant state
Dysmetabolic syndrome

15. Approach to Management
Diabetes management is a team work
Individualize management
Set Target goals
 Glycaemic Targets
 Bp goals
 Lipid goals
Education
Is associated with increased use of primary and
preventive services and lower use of acute,
inpatient hospital services.

16. ADA1 ACE2
HbA1c < 7.0%
(general goal)
≤ 6.5%
Preprandial
plasma glucose
70–130 mg/dL
(3.9–7.2 mmol/L)
< 110 mg/dL
(< 6.1 mmol/L)
Postprandial
plasma glucose
< 180 mg/dL
(< 10.0 mmol/L)
< 140 mg/dL
(< 7.8 mmol/L)
ACE=American College of Endocrinology; ADA=American Diabetes Association; HbA1c=hemoglobin A1c;
Adapted from: 1ADA / EASD consensus statement: Nathan DM, et al. Diabetes Care. 32:193–203;
2American Association of Clinical Endocrinologists, American College of Endocrinology. Endocr Pract. 2002; 8 (Suppl
1): 5–11;
Current Treatment Goals for
Glycaemic Control

17. Life Style Modification
For all patients, advise for
◙ Weight Management (in overweight/obese
patients can improve insulin sensitivity)
◙ Exercise (walking 150 mins / week)
◙ Diet (Provided by a Dietitian)
 Can reduce HbA1C by 1-2%
 Problems
 Poor adherence over time

18. ADA algorithm for the management of type 2
diabetes
Nathan et al., Diabetes Care 2009
SUs other than glibenclamide Insufficient clinical use to be confident regarding safety.
Met=metformin; Pio=pioglitazone; SU=sulfonylurea
Lifestyle and Met +
intensive insulin
At diagnosis:
Lifestyle
+
Metformin
Step 1 Ste p 2 Step 3
Lifestyle and
Met + Pio
No hypoglycaemia
Edema/CHF
Bone loss
Lifestyle and Met
+ DDP-4 inhibitor
Lifestyle and
Met + Pio + SU
Lifestyle and
Met + basal insulin
Tier 2: Less well validated therapies
Lifestyle and
Met + SU
Lifestyle and
Met + basal insulin
Reinforce lifestyle interventions every visit and check HbA1C every
3 -4 months until HbA1C is <7% and then at least every 6 months.
The interventions should be changed if HbA1C is ≥7%
Tier 1: Well validated therapies

19. Life Style +Metformin
Add on Oral Medication
Sulphonylurea
Glibenclamide
Gliclazide MR
TZD
Pioglitazone
15 -30 mg OD
DPP4 inhibitor
Sitagliptin (Januvia)
100 mg OD
Hypoglycemia
Weight gain
Weight gain
Fluid retention
Fractures
?Durability
?Long term risks
A1C > 7 %
Acarbose
PP Hyperg
50-100 mg TDS
Flatulence
Diarrhoea

20. Metformin
Effective & well validated therapy
Choice as initial therapy
Acts by reducing hepatic glucose production
Other
 Reduces appetite & may delay absorption
 Improves peripheral insulin sensitivity
No hypoglycemia and mild weight loss
Start with 500 mg once or twice per day with meals
and increase every few days till reach maximum dose
of 2 gm per day.

21. Oral Medication in Type 2 DM
4- Thiozolidinediones:
● PIOGLITAZONE (15mg)
 Reduce insulin resistance
 Promotes glucose uptake by skeletal muscles and
adipose tissue
 Inhibits hepatic gluconeogenesis
 Used in combination with metformin and
sulphonylurea
 Periodic monitoring of liver enzymes
 Not given in patients with heart failure
 Recently, Debate about increase incidence of Cancer
bladder ??

22. INCRETINS

23. Glucose
in Intestine
DPP-4
Plasma
Mixed Meal
Active
Incretins
Stimulate B cells
(Pancreas) to
secrete Insulin
Inactive Incretin
Renal
Clearance

24. Physiological effects of GLP-1
Bunck MC, et al. Diabetologia. 2010;53 (Suppl 1):S338.

25. Glucagon-like Peptide-1 (GLP-1)
 GLP-1 is secreted throughout the day by intestinal
mucosa in response to oral glucose in the gut.
 GLP-1 causes anabolic actions on the synthesis of
insulin in beta cells by stimulating all steps of insulin
biosynthesis.
 GLP-1 provides continued and augmented release of
insulin for secretion in response to glucose without
overproduction that could lead to hypoglycemia.
 GLP-1 also acts on islet alpha cells, causing strong
inhibition of postprandial glucagon secretion.
 GLP-1 slows gastric emptying and acts on brain to
promote early satiety with reduced food intake

26. Dipeptidyl Peptidase-4 (DPP-4)
• Within minutes of secretion or exogenous
administration, GLP-1 is rapidly degraded by
dipeptidyl peptidase-4 (DPP-4).
• DPP-4 is found in many body tissues, including liver,
renal, and intestinal brush- border membranes;
lymphocytes; and endothelial cells.

27. INCRETINS
The incretin system is impaired in patients with T2DM,
which, as a consequence of its insulinotropic actions,
contributes to fasting and postprandial hyperglycemia.
The impairment of GLP-1 secretion varies directly with
the degree of insulin resistance; those who are more
insulin resistant have a lower rise in GLP-1 in response
to a meal.

28. Medication:
● Exenatide: GLP-1 receptor agonist, SC, twice-daily
● Liraglutide: GLP-1 analog, SC, once daily
● Sitagliptin (Januvia), (DPP-4) inhibitor, 100 mg OD
Other DPP-4 inhibitors, Vildagliptin, Saxagliptin, …
Type 2 diabetes only
 Monotherapy or with Metformin or TZD
 Weight neutral
 Does not cause hypoglycemia

29. Which antidiabetic Drugs are contraindicated or should be
only very cautiously when the following Co-Morbidity is
present?
 Chronic Kidney Failure: Metformin, Acarbose,
Sitagliptin,
Insulin & SUs (reduced
dosage)
 Heart Failure: TZDs
 Osteoporosis: TZDs
 Myocardial Infarction: Hypoglycemias should be
avoided
when Insulin or SUs are taken.

30. Indication of Insulin in Type 2 DM
If HbA1c is ≥ 9 %
After maximum metformin and suphonylurea,
you should consider adding Insulin and taper the
Sulphonylurea.

31. Antiplatelet agents
● Consider Aspirin therapy (75–162 mg/day) as a
primary prevention strategy in those with type 1 or
type 2 diabetes at increased cardiovascular risk (10-
year risk 10%).
This includes most men 50 years of age or women 60
years of age who have at least one additional major
risk factor (family history of CVD, hypertension,
smoking, dyslipidemia, or albuminuria).

32. Statins and Diabetes
Statin therapy should be added to lifestyle therapy,
regardless of baseline lipid levels, for diabetic patients:
 with CVD. (A)
 without CVD who are over the age of 40 years and
have one or more other CVD risk factors. (A)

33. Statins and Diabetes
Low risk patients (without CVD and age of < 40)
Statin therapy should be considered in addition to
lifestyle therapy:
if LDL cholesterol remains above 100 mg/dl or
with multiple CVD risk factors.

34. Hypertension and Diabetes
Goal: < 140 / 80
Choice of Medication:
ACE inhibitors
Angiotensin Receptor Blockers (ARP)

35. •Influenza vaccine (yearly)
•Pneumococcal vaccine (once in lifetime)
Vaccination

36. Targets in DM
Bp < 140 / 80 (ACEi / ARB, if not achieved add
Thiazide)
HbA1C ≤ 7 % (European Diab. Soc. ≤ 6.5 %)
LDL-C < 100 mg/dl (2.6 mmol/L)
HDL-C > 40 mg/dl (males)
> 50 mg/dl (females)
Trig. < 150 mg/dl (1.7 mmol/L)

39. UKPDS
Aim:
To determine whether intensified blood glucose control
with either sulfonylurea or insulin reduces the risk of
Macrovascular or Microvascular complications in type 2
diabet.

40. UKPDS Results 1997
% decrease
P
Conventional
rate
Intensive rate
Cause
12
0.029
46
40.9
Any
Diabetes
related
16
0.052
17.4
14.7
MI
-
0.52
5
5.6
Stroke
-
0.15
1.6
1.1
PVD
25
0.0029
11.4
8.6
Microvascular
Lancet 1998;352:837-853

41. UKPDS Results 2007
Sulfonylurea / Insulin
Intensive Bp lowering
2007
P
2007 RRR %
1997
P
1997 RRR %
End Point
0.001
24
0.0099
25
Microvascular Disease
0.014
15
0.052
16
Myocardial infarction
0.007
13
0.44
6
All Cause Mortality
2007
P
2007 RRR %
1997
P
1997 RRR %
End point
0.20
16
0.0092
37
Microvascular Disease
0.18
11
0.13
21
Myocardial infarction
0.18
11
0.17
18
All Cause Mortality

42. ◙ May 27, 2009 — A new meta-analysis suggests that
intensively controlling blood glucose levels (HbA1c) to
< 7.0%, significantly reduces the risk of (MI) and (CHD)
events and has no effect on all-cause mortality and
Stroke. The findings include UKPDS, ADVANCE, VADT,
ACCORD, and PROACTIVE studies.
◙ The concerns stemmed particularly from the
(ACCORD) and (ADVANCE) and (VADT) which
showed no significant response on Macrovascular
outcomes.
◙ ACCORD, on the other hand, was stopped early
because of an increased risk of death in patients who
underwent intensive blood glucose lowering.

44. PHYSICAL EXAMINATION
 Height and Weight (BMI)
 Blood Pressure (2 readings)
 Fundus Examination ( Hard and soft exudates, new vessel
formation, macular oedema….)
 Cardiac examination
 Lower Limbs:
■ Skin Examination
■ Evaluation of pulses
■ Foot Examination
■ Neurologic Examination

45. LABORATORY EVALUATION
 FPG and 2 hr PP
 Midstream Urine (for Ketones, protein, pus cells,…)
 Urea and Creatinine
 Lipid Profile (total cholesterol, LDLc, HDLc and
triglycerides)
 HbA1C (every 3 m for insulin / every 6 m for controlled)
 Test for Microalbuminuria or
 Albumin to creatinine ratio / 24 hr urine collection
for protein / Creatinine Clearance
 ECG
 Chest X-Ray

46. Yearly Check Up:
Investigations
 HbA1C
 Urea and Creatinine
 Lipid Profile (Cholesterol, Triglyceride, LDL-C and HDL-C)
 Albumin to creatinine ratio / 24 hour urine collection for
protein
Check :
 Eye: Fundus Examination / eye referral
 Feet : Visual inspection and Neurovascular status

48. TREATMENT REGIMENS OF TYPE 1
DM
 Conventional Insulin Therapy
Two injections of NPH and Regular Insulin
 Mixed Insulin
Two injections of 70/30 or 60/40 or 50/50
 Multiple Insulin Injections
►1 or 2 injections of NPH plus 3 injections of
Regular or Lispro Insulin.
►One injection of Glargine or Detemir plus
3 injections of Regular or Lispro Insulin.

49. INSULIN GLARGINE (LANTUS)
 The first clear long-acting insulin
 Acidic (pH of 4) when injected it is neutralized by the
body, causing Glargine crystals to be precipitated and
slowly absorbed.
 It is taken once a day
 Being acidic, cannot be mixed with other insulin

51. 0600 0800 1800
1200 2400 0600
Time of day
20
40
60
80
100
B L D
Basal-Bolus Insulin Treatment
With Insulin Analogues
B=breakfast; L=lunch; D=dinner
Glargine
Lispro, or Aspart
Normal pattern
U/mL

52. Glargine / Lispro
0
10
20
30
40
50
60
B
r
e
a
k
f
a
s
t
N
o
o
n
D
i
n
n
e
r
M
N
Lispro
TID
Glargine
•
Avoids fasting
hyperinsulinaemia and
hypoglycemia
•
Can mimic pancreatic ß-
cell insulin secretion
•
36% had hypoglycemia
vs
50% on NPH.
Dose: Glargine 50% and
Lispro 50%

53. Initiation and adjustment of insulin regimens
Long acting insulin at bedtime 10 U or 0.2 U/Kg
Check FG daily, increase by 2 – 4 U every 3 days until
FG 70 – 130 mg/dl (3.9 – 7.2 mmol/L)
HbA1C ≥ 7% after 2-3 months
If hypoglycaemia occurs, or FG
< 3.9 reduce bedtime by 4
units or 10 % which is greater
If FG in range check before lunch, dinner and
bedtime, add second injection. Begin with 4 U
before each. Adjust by 2 U every 3 days .
Pre-bed is high add
rapid acting insulin
at dinner
Pre-dinner is high
add NPH at
breakfast or rapid
acting at lunch
Pre-lunch is high, add
rapid acting insulin at
breakfast

54. Insulin administration
•
•Do not mix Glargine with other insulin products.
•Insulin site should be clean, but wiping with alcohol is not
needed.
• Syringe reuse acceptable but meticulous attention to
cleanliness is needed.
• Insulin pens improve the dose accuracy.
• Injection site rotation reduces the lipoatrophy.
• Abdomen region has a faster absorption rate than the Arm,
which is faster than the leg.

55. CASE 1
A 53-year-old man presents to your office to check
the results of some routine investigations.
BP 134 / 76 BMI 29.4
FPG : 6.6 mmol/L
In another occasion FPG: 6.2
HbA1C: 6.1 %
What is your management plan?

56. CASE 2
A 48-year-old man presents to your office for routine
checkup for hypertension. Asymptomatic .
On Bisoprolol 5 mg a day.
FH : his father is diabetic
BMI 36 Bp: 148/92
FPG: 10.3 mmol/L U and E: normal
Cholesterol: 5.8 mmol/L LDL: 3.78 HDL: 0.88
Trig. 3.46 mmol/L
What are the next actions?
 Diagnosis
 Choice of medication for HTN, Lipids
 Further work up

57. Case 3
Mohammed a 35 year old referred from A/E because of being
recently diagnosed diabetic. He was put on glibenclamide
5 mg per day. A/E: RBS: 38.3
Urine: Ketones 3+
Glucose 4+
BMI 36 Bp 120 / 72
In clinic RBS by glucocheck: 14.7
Chol. 5.8 LDL-C: 4.3 HDL-C: 0.8
Trig. 2.1
Hb A1C: 11.1 %
24 hr urine for protein: 0.2784 gm (0.01 – 0.15)
Creatinine Clearance: 160.96 ml/min (75 – 125)
How are you going to manage him?

58. CASE 4
A 44-year-old woman presents to your office with 2
month H/O loss of weight and polyuria.
BMI 20
RBS : 24.4 mmol/L
Urine dipstick : glucose: 4+
ketones : nil
Protein : ++
 What is your plan of management ?

59. Case 5
A 22-year-old university student, presents to your
office with one week H/O fatigue and nocturia.
He lost 6 kg per last month.
RBS : 24.6 mmol/L
What is the most important next step to do ?

60. CASE 6
A 52-year-old man is known case of DM presents
to your office for follow up. BMI 33
He is on : Glibenclamide 10 mg po bid
Metformin 1 gm po Bid
FBS : 16.2 mmol/L Cholesterol : 7.3 mmo/L
HbA1C: 11.6 % LDL-C : 4.8 mmol/L
HDL-C : 0.88 mmol/L
Trig. 4.6 mmol/L
U& E : norm.
 How are you going to manage this patient ?

61. American Diabetes
Association
January 2014
Referrence