1. DIABETES MELLITUS
Prof. ADEL A EL-SAYED MD
Chairman Elect
Middle East and North Africa )MENA( Region
)International Diabetes Federation )IDF
Professor of Internal Medicine
Sohag Faculty of Medicine
Sohag-EGYPT

2. The Problem
• Diabetes occurs world-wide and the incidence of
both type 1 and type 2 diabetes are rising; it is
estimated that, in the year 2000, 171 million
people had diabetes, and this is expected to
double by 2030.
• This global pandemic principally involves type 2
diabetes, to which several factors contribute,
including greater longevity, obesity,
unsatisfactory diet, sedentary lifestyle and
increasing urbanizations.

3. 3
Diabetes: the growing global
burden
1
Prevalence estimates of diabetes mellitus 2025
2003
2001
2000
No data
< 2%
2–5%
5–8%
8–11%
11–14%
14–17%
> 17%
International Diabetes Federation )IDF(:2
• Diabetes currently affects nearly 250 million people worldwide
• It is expected to affect 380 million by 2025
1
Adapted from IDF. E-Atlas. Available at: www.eatlas.idf.org )accessed 26.12.08(.
2
Diabetes Atlas, third edition© International Diabetes Federation, 2006.

4. The IDF Diabetes Atlas
5th Edition
December 2011
A summary of the figures and key
findings

5. The global burden
 366 million people have diabetes in 2011; by 2030 this will have
risen to 552 million
 The number of people with type 2 diabetes is increasing in every
country
 80% of people with diabetes live in low-and middle-income countries
 The greatest number of people with diabetes are between 40 to 59
years of age
 183 million people (50%) with diabetes are undiagnosed
 Diabetes caused 4.6 million deaths in 2011
 Diabetes caused at least USD 465 billion dollars in healthcare
expenditures in 2011; 11% of total healthcare expenditures in adults
(20-79 years)
 78,000 children develop type 1 diabetes every year

7. The Top 10s
((number of people with diabetes

8. The Top 10s
(% (prevalence

9. Undiagnosed diabetes

10. Healthcare
expenditures
• USD 465 billion
spent on
healthcare for
diabetes
• 11% of all
healthcare
spending is for
diabetes
• USD 1,274 is
spent on diabetes
care per person
with diabetes in
2011

12. Diabetes and Tuberculosis
• Focused on the linkages between the
two diseases and a review of the
evidence
• Calculated the attributable cases of
tuberculosis to diabetes
• Highlights areas where there is a high
double burden

14. Key Messages
1. Diabetes is a huge and growing problem, and the
costs to society are high and escalating
2. Diabetes is a neglected development issue,
affecting all countries
3. There are cost-effective solutions to reverse the
global diabetes epidemic
4. Diabetes is not only a health issue, its causes are
multi-sectoral and it requires a multi-sectoral
response
5. The UN High-level Meeting is not the end of
international commitments on diabetes; it is the
start of concerted and coordinated action

15. AETIOLOGICAL CLASSIFICATION
OF DIABETES MELLITUS
• Type 1 diabetes
• Type 2 diabetes
• Gestational diabetes
• Other forms endocrine diseases such as
acromegaly or Cushing's syndrome
unusual genetic diseases

16. AETIOLOGY AND PATHOGENESIS OF
DIABETES
• In both of the common types of diabetes, environmental
factors interact with genetic susceptibility to determine
which people develop the clinical syndrome.
• However, the underlying genes, precipitating
environmental factors and pathophysiology differ
substantially between type 1 and type 2 diabetes.
• Type 1 diabetes (previously IDDM) is invariably
associated with profound insulin deficiency requiring
replacement therapy.
• Type 2 diabetes (previously NIDDM) patients retain the
capacity to secrete some insulin but exhibit impaired
sensitivity to insulin (insulin resistance) and can usually
be treated without insulin replacement therapy.

17. TYPE 1 DIABETES
Pathology
Type 1 diabetes is a slowly progressive T cell-mediated
autoimmune disease. Family studies have produced
evidence that destruction of the insulin-secreting cells in
the pancreatic islets takes place over many years.
Hyperglycaemia accompanied by the classical symptoms
of diabetes occurs only when 70-90% of ß cells have
been destroyed.
The pathological picture in the pre-diabetic pancreas in
type 1 diabetes is characterised by: 'insulitis'
Islet cell antibodies can be detected before the clinical
development of type 1 diabetes
Type 1 diabetes is associated with other autoimmune
disorders, including thyroid disease, coeliac disease,
Addison's disease, pernicious anaemia and vitiligo.

18. Environmental factors
• Although genetic susceptibility appears to be a
prerequisite for the development of type 1 diabetes, the
concordance rate between monozygotic twins is less
than 40%and environmental factors have an important
role in promoting clinical expression of the disease.
• The evidence that viral infection might cause some forms
of type 1 diabetes is derived from studies where virus
particles known to cause cytopathic or autoimmune
damage to ß cells have been isolated from the pancreas.
• Several viruses have been implicated, including mumps,
Coxsackie B4, retroviruses, rubella (in utero),
cytomegalovirus and Epstein-Barr virus.

19. Environmental factors
• Circumstantial evidence supports the proposition
that dietary factors may influence the
development of type 1 diabetes.
• Bovine serum albumin (BSA), a major
constituent of cow's milk, has been implicated in
triggering type 1 diabetes, since children who
are given cow's milk early in infancy are more
likely to develop type 1 diabetes than those who
are breastfed.
• Other factors.

20. Metabolic disturbances in type 1
diabetes
• Profound insulin deficiency is associated with metabolic
sequelae.
• Hyperglycaemia leads to glycosuria and dehydration.
• Unrestrained lipolysis and proteolysis result in weight
loss, increased gluconeogenesis and ketogenesis.
• When generation of ketone bodies exceeds the capacity
for their metabolism, ketoacidosis results.

21. TYPE 2 DIABETES
Pathology
• Type 2 diabetes is a more complex condition than type 1
diabetes because there is a combination of resistance to
the actions of insulin in liver and muscle together with
impaired pancreatic ß-cell function leading to 'relative'
insulin deficiency
• Insulin resistance appears to come first, and leads to
elevated insulin secretion in order to maintain normal
blood glucose levels.
• However, in susceptible individuals the pancreatic ß cells
are unable to sustain the increased demand for insulin
and a slowly progressive insulin deficiency develops.

22. 22
Type 2 diabetes is a progressive disease: early
intervention is critical
Macrovascular complications
Microvascular complications
β-cell function
Insulin
resistance
Blood
glucose
–10 Prevention 0 Treatment 10+ Years
Diagnosis
IFG/IGT Type 2 diabetes
IFG: impaired fasting glucose
IGT: impaired glucose tolerance
Adapted from DeFronzo RA. Med Clin N Am 2004;88:787–835.

23. UKPDS: progressive decline of
β-cell function over time
100
80 Start of treatment
β-cell function )%(
60
40
20 P < 0.0001
0
–10 –9 –8 –7 –6 –5 –4 –3 –2 –1 1 2 3 4 5 6
Time from diagnosis )years(
HOMA model, diet-treated (n = 376)
Adapted from Holman RR. Diabetes Res Clin Pract 1998; 40 (Suppl.):S21–S25.

24. Metabolic disturbances in type 2
diabetes
• Patients with type 2 diabetes have a slow onset
of 'relative' insulin deficiency.
• Ketoacidosis are rare.
• Glycosuria occurs when the blood glucose
concentration exceeds the renal threshold.
• The severity of the classical 'osmotic' symptoms
of polyuria and polydipsia is related to the
degree of glycosuria.
• Thus, patients are often asymptomatic, but
usually present with a long history (typically
many months) of fatigue, with or without osmotic
symptoms.

25. INVESTIGATIONS
• URINE TESTING: Glucose, Ketones
Protein.
• BLOOD TESTING: Glucose, Glycated
haemoglobin, Blood lipids.
• The diagnostic criteria for diabetes
mellitus

26. Clinical assessment
• Hyperglycaemia causes a wide variety of
symptoms.
• The classical symptoms of thirst, polyuria,
nocturia and rapid weight loss are
prominent in type 1 diabetes, but are often
mild or absent in patients with type 2
diabetes.
• fatigue and malaise.
• increased susceptibility to infection.

27. Clinical assessment
• The physical signs in patients with type 2
diabetes at diagnosis depend on the mode of
presentation:
• More than 70% are overweight, and obesity
may be central (truncal or abdominal).
• Hypertension is present in at least 50% of
patients with type 2 diabetes.
• Although hyperlipidaemia is also common, skin
lesions such as xanthelasma and eruptive
xanthomas are rare.

28. Patient Education
• Outpatient education: achieved by a
multidisciplinary team (doctor, dietitian,
specialist nurse and podiatris).
• Inpatient education: when insulin
injections are needed.
• Self-assessment of glycaemic control:
urine, SMBG.
• Education of treatment targets: BG, BP,
Serum lipids.

29. Advice to patients with IGT
• Lifestyle advice.
• Monitoring of blood glucose level.
• Other cardiovascular risk factors should
be treated aggressively.

30. Management
• dietary/lifestyle modification (diet and
excercise).
• oral anti-diabetic agents.
• insulin injections.
• In parallel with treatment of
hyperglycaemia, other risk factors for
complications of diabetes need to be
addressed (hypertension, dyslipidaemia
and advice on smoking cessation).

31. ORAL ANTI-DIABETIC DRUGS
• Although their mechanisms of action are
different, most depend upon a supply of
endogenous insulin. No role in treatment of type
1 DM.
• The sulphonylureas and the biguanides have
been the mainstay of treatment for many years
and have the strongest evidence of preventing
complications of diabetes.
• Newer agents include the insulin sensitizers the
thiazolidinediones, the a-glucosidase inhibitors
and incretins.
• Primary and secondary failure.

32. SULPHONYLUREAS
• Mechanism of action: The principal effect of
sulphonylureas is to stimulate the release of insulin from
the pancreatic ß cell (insulin secretagogue).
• Indications for use: valuable in the treatment of non-
obese patients with type 2 diabetes who fail to respond
to dietary measures alone.
• The main differences between the individual compounds
lie in their potency, duration of action and cost.
• Tolbutamide and chlorpropamide are now rarely used.
• gliclazide and glipizide, glibenclamide and glimepride are
used more often now.
• Side effects.

33. BIGUANIDES
• Metformin is the only biguanide available.
• Indications for use.
• Advantages.
• Side effects and contraindications.
• Dose and method of administration.

34. ALPHA-GLUCOSIDASE INHIBITORS
• The a-glucosidase inhibitors delay
carbohydrate absorption in the gut.
• Acarbose or miglitol is available and is
taken with each meal.
• Lower post-prandial blood glucose and
modestly improve overall glycaemic
control.
• The main side-effects are flatulence,
abdominal bloating and diarrhoea.

35. THIAZOLIDINEDIONES
• These drugs (also called TZD drugs, 'glitazones'
or PPAR? agonists) bind and activate
peroxisome proliferator-activated receptor.
• A nuclear receptor present mainly in adipose
tissue that regulates the expression of several
genes involved in metabolism, and work by
enhancing the actions of endogenous insulin.
• Plasma insulin concentrations are not increased
and hypoglycaemia is not a problem.
• Types, price, indications, and side effects.

36. INCRETIN MIMETICS
• A new class of therapeutic agents is being
developed for treatment of type 2 diabetes.
• The secretion of insulin in response to a rise in
blood glucose is greater when glucose is given
by mouth, rather than by intravenous infusion.
• In part this is caused by secretion of gut
hormones, or incretins, which potentiate
glucose-induced insulin secretion.
• Glucagon-like peptide (GLP-1) is an incretin
hormone which stimulates insulin secretion in a
glucose-dependent manner, thus hypoglycaemia
is unlikely.

37. INCRETIN MIMETICS
• In addition, GLP-1 suppresses glucagon
secretion, delays gastric emptying, reduces
appetite and encourages weight loss.
• It has to be given by injection.
• As GLP-1 is rapidly degraded by the enzyme,
dipeptidyl peptidase IV, inhibitors of this enzyme
will have to be given to prolong its biological
effect.
• Alternatively, long-acting GLP-1 analogues are
being developed. These include liraglutide and
exenatide (synthetic exendin-4).
• DPP4 inhibitors.

38. INSULIN
• History, manufacture and formulation.
• Regular insulin.
• The duration of action of short-acting,
unmodified insulin ('soluble' or 'regular' insulin),
which is a clear solution, can be extended by the
addition of protamine and zinc at neutral pH
(isophane or NPH insulin) or excess zinc ions
(lente insulins).
• Pre-mixed formulations.
• Insulin analogues.

39. INSULIN
• Insulin delivery.
• Insulin regimens.