Diabetes mellitus

1. Diabetes Mellitus
Dr. S. Parasuraman
Faculty of Pharmacy,
AIMST University, Malaysia
Risk factors

2. World Health Day 2016
7 April

3. Diabetes Mellitus
• As per the WHO, diabetes mellitus (DM) is defined as a
hetrogeneous metabolic disorder characterised by
common feature of chronic hyperglycaemia with
disturbance of carbohydrate, fat and protein metabolism.
• Diabetes is a chronic disease that occurs either when the
pancreas dose not produce enough insulin or the body
cannot effectively use the insulin it produces. Uncontrolled
diabetes may lead to serious damage to many body
systems, especially the nervous and blood vessels.

4. DM – Facts sheet June, 2016 by WHO
• The number of people with diabetes has risen from 108
million in 1980 to 422 million in 2014.
• Global prevalence of diabetes among adults over 18 years
of age has raisin from 4.7% in 1980 to 8.5% in 2014.
• Diabetes is a major cause of blindness, kidney failure, heart
attacks, stroke and lower limb amputation.
• In 2012 an estimated 1.5 million deaths were directly
caused by diabetes and another 2.2 million deaths were
attributable to high glucose.
• Healthy diet, regular physical activity, maintaining normal
body weight and avoiding tobacco use are way to prevent
or delay the onset of type 2 diabetes.

5. Etiologic Classification of DM
Type Sub-type
Type 1 Diabetes mellitus
(10%)
Type IA DM: Immune-
mediated
Type IB DM: Idiopathic
Type 2 Diabetes mellitus
(80%)
Other specific types of
diabetes (10%)
• Genetic defect of β-cell function due to mutations in
various enzymes
• Genetic defect in insulin action
• Endocrinopathies
• Drug- or chemical-induced
• Infections
• Uncommon forms of immune-mediated DM (stiff man
syndrome, anti-insulin receptor antibodies)
• Other genetic syndromes (e.g. Down's syndrome,
Klinefelter's syndrome, Turner's syndrome)
Gestational diabetes
mellitus

6. Type 1 Diabetes mellitus
• Type 1 DM occurs commonly in patients under 30
years of age, autoimmune destruction of β-cells can
occur at any age.

7. Type 2 Diabetes mellitus
• It constitutes about 80% cases of DM.
• Type 2 DM earlier called non-insulin-dependent, or
maturity-onset diabetes (MOD).
• Type 2 DM predominantly affects older individuals, it is
now known that it also occurs in obese adolescent
children.

8. Major Risk Factors for Type 2 DDM
• Family history of type 2 DM
• Obesity
• Habitual physical inactivity
• Race and ethnicity (Blacks, Asians, Pacific Islanders)
• Previous identification of impaired fasting glucose or
impaired
• glucose tolerance
• History of gestational DM or delivery of baby heavier than 4
kg
• Hypertension
• Dyslipidaemia (HDL level < 35 mg/dl or triglycerides > 250
mg/dl)
• Polycystic ovary disease and acanthosis nigricans
• History of vascular disease

9. Gestational DM
• About 4% pregnant women develop DM due to metabolic
changes during pregnancy.
• They revert back to normal glycaemia after delivery, these
women are prone to develop DM later in their life.

10. Pathogenesis
• Depending upon etiology of DM, hyperglycaemia may
result from the following:
– Reduced insulin secretion
– Decreased glucose use by the body
– Increased glucose production.

11. Normal Insulin Metabolism
A: Pathway of normal insulin synthesis and release in β-cells of pancreatic islets.
B: Chain of events in action of insulin on target cell.

12. Type 1 Diabetes mellitus

13. Type 1 Diabetes mellitus
• It constitutes about 10% cases of DM.
• Type 1 DM earlier called Insulin-dependent, or juvenile-
onset diabetes.
• It is called insulin dependent DM (IDDM) because it was
known that these patients have absolute requirement for
insulin replacement as treatment.
• Subtype 1A (immune-mediated) DM characterised by
autoimmune destruction of β-cells which usually leads to
insulin deficiency.
• Subtype 1B (idiopathic) DM characterised by insulin
deficiency with tendency to develop ketosis but these
patients are negative for autoimmune markers.

14. Pathogenesis of Type 1 DM
• Type 1 DM is destruction of β-cell mass, usually leading to
absolute insulin deficiency.
• Genetic susceptibility: Type 1A DM involves inheritance of
multiple genes to confer susceptibility to the disorder [identical
twins- has chances of 50% development of Type1A DM to second
twin; genetic predisposition to type 1A DM have the susceptibility
gene located in the HLA region of chromosome 6 (MHC class II region),
particularly HLA DR3, HLA DR4 and HLA DQ locus].
Short arm Long arm

15. Pathogenesis of Type 1 DM
• Autoimmune factors: Immunologic abnormalities such as
• presence of islet cell antibodies against glutamic acid
decarboxylase (GAD) and insulin
• insulitis [occurrence of lymphocytic infiltrate in and around
the pancreatic islets]
• selective destruction of βcells
• role of T cell-mediated autoimmunity
• role of other autoimmune diseases [20% of Type 1 DM
associated with Graves’ disease, Addison’s disease,
Hashimoto’s thyroiditis, pernicious and anaemia]
• Immunosuppressive therapy

16. Pathogenesis of Type I DM
• Environmental factors: Certain viral (mumps, measles,
coxsackie B virus, cytomegalovirus and infectious
mononucleosis), chemicals (alloxan, streptozotocin and
pentamidine) dietary proteins (bovine milk proteins) share
antigenic properties with human cell surface proteins and
trigger the immune attack on β-cells by a process of
molecular mimicry [β-cells act as autoantigens and activate
CD4+ T lymphocytes].

17. Type 2 Diabetes mellitus

18. Pathogenesis of Type 2 DM
• Genetic factors: No definite and consistent genes have
been identified for the development of type 2 DM.
Multifactorial inheritance is the most important factor in
development of type 2 DM.
• Constitutional factors: Certain environmental factors such
as obesity, hypertension, and level of physical activity play
contributory role and modulate the phenotyping of the
disease.
• Insulin resistance: One of the most prominent metabolic
features of type 2 DM is the lack of responsiveness of
peripheral tissues to insulin, especially of the skeletal
muscle and liver. Obesity, in particular, is strongly
associated with insulin resistance and hence type 2 DM.

19. Pathogenesis of Type 2 DM
• Insulin resistance:.

20. • Insulin resistance:
Insulin resistance plays a major
pathogenic role in the
development of the metabolic
syndrome, which may include any
or all of the following:
• Hyperinsulinemia
• Type 2 diabetes or glucose
intolerance
• Central obesity
• Hypertension
• Dyslipidemia that includes high
triglyceride levels
• Low HDL-C level and small,
dense low-density lipoprotein
(LDL) particles
• Hypercoagulability
characterized by an increased
plasminogen activator
inhibitor–1 (PAI-1) level
Pathogenesis of Type 2 DM

21. Pathogenesis of Type 2 DM
• Impaired insulin secretion: Hyperinsulinaemia, failure of β-
cell function, glucose toxicity and lipotoxicity are worsen
the islet cell function.
• Increased hepatic glucose synthesis: Increased hepatic
synthesis of glucose which contributes to hyperglycaemia.

22. Complications of diabetes mellitus
• Acute Metabolic Complications
– Diabetic Ketoacidosis (DKA)
– Hyperosmolar Hyperglycaemic Nonketotic Coma (HHS)
– Hypoglycaemia
• Late Systemic Complications
– Atherosclerosis
– Diabetic microangiopathy
– Diabetic nephropathy
– Diabetic neuropathy
– Diabetic retinopathy
– Infections

23. Diagnosis of diabetes
• Urine testing (Benedict’s qualitative test, Tests for ketone
bodies [Ketonuria])
• Single blood sugar estimation (O-toluidine, Somogyi-
Nelson and glucose oxidase]
• Oral glucose tolerance test
• Other tests (Glycosylated haemoglobin [HbA1C], Glycated
albumin, extended GTT, intravenous GTT, cortisone-primed
GTT, insulin assay, proinsulin assay, C-peptide assay, islet
autoantibodies, screening for diabetes-associated
complications)

24. Diagnosis of diabetes
Diagnosis of Diabetes by Oral GTT (as per American Diabetes Association, 2007).
Plasma Glucose Value Diagnosis
FASTING (FOR > 8 HOURS) VALUE
Below 100 mg/dl (< 5.6 mmol/L) Normal fasting value
100-125 mg/dl (5.6-6.9 mmol/L) Impaired fasting glucose (IFG)
126 mg/dl (7.0 mmol/L) or more Diabetes mellitus
TWO-HOUR AFTER 75 GM ORAL GLUCOSE LOAD
< 140 mg/dl (< 7.8 mmol/L) Normal post-prandial GTT
140-199 mg/dl (7.8-11.1 mmol/L) Impaired post-prandial glucose tolerance
200 mg/dl (11.1 mmol/L) or more Diabetes mellitus
RANDOM VALUE
200 mg/dl (11.1 mmol/L) or more Diabetes mellitus in a symptomatic patient

25. Beat Diabetes
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