2. DIABETES MELLITUS BY Dr. HUSSEIN SAAD, MRCP (UK)
Consultant Family Medicine
Assistant Clinical Professor
KKUH

3. DEFINITION
A group of metabolic disorders characterized by hyperglycemia resulting from defects in insulin secretion, insulin action or both.

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 subjects
conducted between 1995 and 2000 in KSA.
The examining age group, 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): 

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< ).
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): 

7. DIAGNOSIS
A 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.

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.

9. 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

10. 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

11. Impaired Glucose Tolerance
● There is growing evidence that at glucose levels
above normal but below the diabetes threshold
diagnostic now referred to as pre-diabetes.
● There is a substantially increased risk of
cardiovascular disease (CVD) and death.
1- The DECODE Study Group: Glucose tolerance and cardiovascular mortality: comparison of fasting and 2-hour diagnostic criteria. Arch Intern Med 161:397–405, 2001
2- Saydah SH, Loria CM, Eberhardt MS, Brancati FL: Subclinical states of glucose intolerance and risk of death in the U.S. Diabetes Care 24:447–453, 2001

12. Impaired Glucose Tolerance
■ In the Finnish study, 522 middle-aged obese (mean BMI 31 kg/m2) subjects with IGT were randomized to receive either brief diet and exercise counseling (control group) or intensive individualized instruction on weight reduction, food intake, and guidance on increasing physical activity (intervention group).
After an average follow-up of 3.2 years, there was a 58% relative reduction in the incidence of diabetes in the intervention group compared with the control subjects.
Tuomilehto J et al Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med 344:1343–1350, 2001

13. Impaired Glucose Tolerance
■ Three diabetes prevention trials used pharmacological therapy, and all have reported a significant lowering of the incidence of diabetes.
1- The Biguanide Metformin reduced the risk of diabetes by 31% in
the DPP (1)
2- The -Glucosidase Inhibitor Acarbose reduced the risk by 32% in the
STOP-NIDDM trial (2)
3- The Thiazolidinedione Troglitazone reduced the risk by 56% in the
TRIPOD study (3)
1- Diabetes Prevention Research Group: Reduction in the evidence of type 2 diabetes with life-style intervention or metformin. N Engl J Med 346:393–403, 2002
2- Chiasson JL et al for the STOP-NIDDM Trial Research Group: Acarbose for prevention of type 2 diabetes mellitus: the STOP-NIDDM randomised trial. Lancet 359:2072–2077, 2002
3- Diabetes 51:2796–2803, 2002

15. Oral medication for type 2 DM
1- Sulphonylurea group:
• Glibenclamide
• Gliclazide
• Glipizide
Action: stimulate the pancreace to secrete
insulin.
Note: Gliclazide is suitable for patients
with impaired hepatic and renal
functions.

16. Oral Medication for type 2 DM
2- Biguanide Group (METFORMIN)
Action: ▪ Inhibit the process of Gluconeogenesis.
▪ Increasing the peripheral utilization of
Glucose.
▪ It acts only in the presence of insulin.
Precaution: Not given in patients with impaired
liver or renal functions (Hold if creatinine
> 160 in males and > 150 mmol/l in
females), severe infections, .

17. Oral Medication for type 2 DM
3- Alpha Glucosidase Inhibitors (ACARBOSE)
■ Used for Post Prandial Hyperglycaemia
Action: inhibit the absorption of carbohydrate.
Side effects: flatulance, distension, soft
stool,..

18. Oral Medication for type 2 DM
4- Meglitinides ( REPAGLINIDE )
■ Used for Post Prandial Hyperglycaemia
Action: • Similar in action to Sulphonylurea
• Rapid onset of action
•Taken immediately before meals
■ Used as Monotherapy or in combination with
Metformin

19. Oral Medication for type 2 DM
4- Thiozolidinediones:
● ROSIGLITAZONE
● PIOGLITAZONE
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

21. INCRETINS

22. Glucagon-like Peptide-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 promotes early satiety with reduced food intake

23. Dipeptidyl Peptidase-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.

24. 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.

25. The American Association of Clinical Endocrinologists (AACE) guidelines make it clear that Incretins can be used early and are not limited to third- or fourth-line therapy for T2DM

26. Medication:
Two agents are currently available in the US that act upon the Incretin hormone system –
● Exenatide (Byetta), a twice-daily glucagon-like peptide-1 (GLP-1) receptor agonist.
● Sitagliptin (Januvia), a dipeptidyl peptidase-4 (DPP-4) inhibitor.
● Agents are currently under review by (FDA). These include the once-daily human GLP-1 analog liraglutide and the DPP-4 inhibitors Alogliptin, Saxagliptin, and Vildagliptin.

29. 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

30. UKPDS Results
% 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:

34. MANAGEMENT OF TYPE 2 DM Obese patients:
Diet and Exercise should be offered for all patients for 2 months.
Obese patients:
■ METFORMIN is the drug of choice
Start with 500 mg PO three times a day up
up to 850 mg or 1 gm PO TDS.
■ If not controlled add Sulphonylurea or
Glitazones

35. MANAGEMENT OF TYPE 2 DM Non-Obese patients Diet and Exercise Metformin
Add Sulphonylurea (e.g. Glibenclamide or Gliclazide)
In secondary failure, consider shifting to Insulin

36. PHYSICAL EXAMINATION Height and Weight Blood Pressure
Fundus Examination
Cardiac examination
Lower Limbs:
■ Skin Examination
■ Evaluation of pulses
■ Foot Examination
■ Neurologic Examination

37. LABORATORY EVALUATION
FPG and 2 hr PP
Midstream Urine
Urea and Creatinine
Lipid Profile (total cholesterol, LDLc, HDLc and triglycerides)
HbA1c
24 hr urine collection for protein
ECG
Chest X-Ray

39. 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
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

40. 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

41. 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.

42. Targets in DM
Bp < 130 / 80
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)

43. CASE 1
A 50-year-old man presents to your office to check the results of some routine investigations.
FPG : 6.6 mmol/L
In another occasion FPG: 6.2
what is your diagnosis ?
what further investigations are you going to do ?

44. How are you going to deal with him?
CASE 2
A 48-year-old man presents to your office for routine checkup for hypertension. Asymptomatic .
On Atenolol 50 mg a day.
FH : his father is diabetic
BMI Bp: 150/94
FPG: 14.6 mmol/L U and E: normal
Cholesterol: mmol/L
Trig mmol/L
How are you going to deal with him?

45. CASE 3
A 44-year-old woman presents to your office with 2 month H/O loss of weight and polyurea.
BMI
RBS : 24.4 mmol/L
Urine dipstick : glucose: 4+
ketones : nil
Protein : ++
what is your diagnosis ?
what is your management ?

46. Case 4
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 ?

47. CASE 5
A 52-year-old man is known case of DM presents to your office for follow up.
He is on : glibenclamide 10 mg po bid
Metformin 1 gm po tid
FBS : mmol/L Cholesterol : 7.3 mmo/L
2hPP: 21.4 mmol/L LDL-C : mmol/L
HDL-C : mmol/L
Trig mmol/L
U& E : norm.
BMI 33
? :
How are you going to manage this patient ?

48. THANK YOU