1. DIABETES MELLITUS
• Diabetes mellitus is a clinical syndrome. which is
characterized by the presence of hyperglycaemia (mellitus
being Latin for ‘sweet’).
• The prevalence of diabetes is rising.
• Globally, it is estimated that 463 million people had diabetes
in 2019. This figure is expected to reach 700 million by 2045.
2. • All forms of diabetes are ultimately a consequence of absolute or
relative insulin deficiency.
• Type 2 diabetes accounts for around 90% of cases, while type 1
diabetes accounts for most of the remainder.
• Although type 1 and type 2 diabetes share the clinical phenotype of
hyperglycaemia and carry risks of similar complications, but their
aetiology and pathophysiology are very different
3. •Diagnostic criteria for diabetes and pre-diabetes
Definitions of ‘pre-diabetes’
- impaired fasting glucose:
fasting plasma glucose between 110 to126 mg/dl .
- impaired glucose tolerance:
fasting plasma glucose <126 mg/dL and 2-hr glucose after
75 g oral glucose drink ≥140 mg/dL and <200 mg/dL.
- HbA1c:
39–47 mmol/mol (American Diabetes Association).
4. • Diabetes is confirmed If
-plasma glucose in random sample or 2-hrs after a 75 g glucose load
≥200 mg/dL)or
- fasting plasma glucose ≥126 mg/dL or
- HbA1c ≥6.5 %
-In asymptomatic patients, two diagnostic tests are required to confirm
diabetes.
5. Oral glucose tolerance test (OGTT)
• Preparation before test
-Unrestricted carbohydrate diet for 3 days
- Fasted overnight for at least 8 hours
-Rest for 30 mins
- Remain seated for the duration of the test, with no smoking
• Sampling
-Measure plasma glucose before and 2 hours after a 75 g oral
glucose drink.
6. Aetiological classification of diabetes mellitus
1)Type 1 diabetes
2)Type 2 diabetes
3)Other specific types diabetes
- Genetic defects of β-cell function
- Genetic defects of insulin action (e.g., lipodystrophies)
- Pancreatic disease (e.g. pancreatitis, pancreatectomy, neoplastic
haemochromatosis, fibrocalculous pancreatopathy)
- Excess endogenous production of hormonal antagonists to insulin,
e.g.:
Growth hormone – acromegaly
Glucocorticoids – Cushing’s syndrome
9. Type 1 diabetes
Pathogenesis
- Type 1 diabetes is an immune-mediated disorder involving T-
cell destruction of β cells in the pancreatic islets (‘insulitis’).
- The natural history of type 1 diabetes is classically based on a
‘gene-environment interaction’ model, i.e. genetically susceptible
individuals develop β-cell autoimmunity following exposure to an
environmental trigger.
11. Genetic predisposition
• Type 1 diabetes is strongly influenced by genetic factors, but does not
follow a simple Mendelian pattern of inheritance.
• Monozygotic twins have a concordance rate of 30%–50% for the
condition, while dizygotic twins have a concordance of 6%–10%.
• Children of mothers with type 1 diabetes have a 1%–4% risk of
developing type 1 diabetes, but children of fathers with type 1 diabetes
have a 10% risk.
• If both parents have the condition the risk is up to 30%.
• The HLA haplotypes DR3 and/or DR4 are associated with increased
susceptibility to type 1 DM.
13. Clinical course of type 1 diabetes
• The natural course of type 1 diabetes involves initially a loss of
First-phase insulin secretion, followed by a period of pre-
diabetes and then clinically undiagnosed diabetes,
• Before a diagnosis of diabetes is made more than 80%–90% of β-
cell mass has usually been destroyed.
• While type 1 diabetes is classically thought of as a disease of
children and young adults ,But it can manifest at any age.
• Over 40% of cases developing in adults over 30 years of age
14.
15. Latent autoimmune diabetes of adulthood (LADA)
• LADA also known as a slowly evolving immune-mediated diabetes of
adults.
• This is essentially a subset of type 1 diabetes with usually a single islet
autoantibody present in high titre (usually anti-GAD), greater retention of
β-cell function and hyperglycaemia that does not require immediate
commencement of insulin therapy.
• Affected individuals often have features of the metabolic syndrome.
• managed with a working diagnosis of type 2 diabetes, but requires having
progressed more rapidly to requiring insulin treatment than is typical for
type 2 diabetes
16. Type 2 diabetes
• Type 2 diabetes is a heterogeneous condition characterized by
varying degrees of insulin resistance and β-cell dysfunction,
commonly associated with obesity.
• Approximately 40% of overall type 2 diabetes risk is determined
by genetic factors, with the rest due to environmental (acquired)
factors.
• Insulin resistance and β-cell dysfunction have both genetic and
environmental determinants .
17. • Individuals at high risk of type 2 diabetes usually have a degree of genetic
predisposition to either
- pancreatic β-cell dysfunction (measured as β-cell glucose sensitivity),
- insulin resistance (measured as insulin-mediated glucose uptake) or
both.
- As β-cell function continues to decline over time, there is an escalating
requirement for glucose-lowering therapy.
-In the most extreme form, there is pancreatic β-cell ‘exhaustion’ and, as
in type 1 diabetes, insulin therapy is required to prevent ketoacidosis.
18. Risk factors for type 2 diabetes
• Genetic predisposition
- The largest population genetic effect described to date is a variation in
TCF7L2 (a transcription factor involved in glucose metabolism in pancreas
and liver).
• Lifestyle factors and obesity
• Age-Type 2 diabetes is more common with increasing age.
• Ethnicity-white ethinicity peoples are lesser risk compared to black
ethinicity population.
• Environmental factors are also important, such as cultural practices and
socio-economic status, which in turn are reflected in diet, physical
activity and levels of obesity
19. Pancreatic diabetes
• It may be caused by acute or chronic pancreatitis, either due to alcohol
excess or to gall bladder (stone) disease.
• While chronic pancreatitis may be associated with recurrent abdominal
pain, it is important to be aware of the possibility of pancreatic exocrine
deficiency in all cases of diabetes;
• this can be detected by screening for low faecal enzyme elastase in a
stool sample, particularly in the presence of chronic diarrhoea .
• Adequate oral pancreatic enzyme replacement can reduce abdominal
pain, improve absorption of ingested nutrients and enhance well-being.
20. Maturity-onset diabetes of the young (MODY)
• It is a monogenic disorders of the β cell of pancrease.
• It develops under the age of 25 years . It is dominantly inherited and
MODY has been recognised with multiple single gene subtypes.
• One form is caused by a mutation in the β-cell glucose sensor enzyme
glucokinase and affected individuals have an altered set-point for
glucose. Glucokinase MODY results in a high fasting glucose 99mg/dL, but
a normal post-prandial response and slight elevation of HbA1c
21. • The other forms of MODY are mostly caused by defective
transcription factors that play a key role in β-cell development and
function (hepatocyte nuclear factor (HNF) 1α, 1β and 4α).
• Patients with transcription factor MODY develop progressive diabetes
in adolescence or early adulthood and the diabetes is progressive,
requiring oral glucose-lowering therapy before eventually needing
insulin.
• Patients with HNF1α and 4α MODY are extremely sensitive to
sulphonylureas, so this is the treatment of choice for these
individuals.
22. Management of diabetes
• The aims for both types 1 and 2 diabetes are initially to relieve
osmotic symptoms and then to minimise the risks of long-term
microvascular and macrovascular complications.
• Microvascular complications are prevented by targeting
hyperglycaemia, but control of macrovascular complications also
requires management of associated risk factors, particularly
hypertension, dyslipidaemia and cigarette smoking.
23. • Type 2 diabetes Where there are no ‘red flags’ of ketosis or
rapid weight loss,
• initial management of type 2 diabetes involves dietary and
lifestyle advice, which should aim at inducing remission of
the condition.
• However, adding in oral glucose-lowering drugs is more
likely to be required at an early stage for those who have
symptomatic hyperglycaemia or a high HbA1c.
24. MEDICAL NUTRITION THERAPY AND PHYSICAL ACTIVITY
• Example-Low calorie,
-carbohydrate controlled diet,
-exercise
• Mechanism of action-decreases insulin resistance ,
-increases insulin secretion
• Advantages-other health benefits
• Disadvantages-compliance difficult,
-long term success low
25. Factors that determine which of these drugs
should be prescribed first –
• individual profile (severity of initial symptoms, degree of obesity)
• glucose-lowering efficacy
• protective properties in relation to cardiovascular and renal complications.
• adverse effect profile (hypoglycaemia, weight gain)
• renal function
• drug factors (mechanism of clearance/metabolism)
• ability or willingness to self-inject
• occupation (e.g. driving, working at heights)
• cost: important whether covered by a national health-care system or not.
26. ORAL -HYPOGLYCEMIC DRUGS
Biguanides
• Example-Metformin
• Mechanism of action-decrease hepatic glucose production
-increases insulin sensitivity
-influence gut function
. Advantages-weight neutral
-do not cause hypoglcemia
-inexpensive
-extensive experience
-decreases cv events
. Disadvantages-diarrhea,nausea,lactic acidosis,vit B12 deficiency
34. AMYLIN AGONISTS
• Example-Pramlintide
• Mechanism of action-slow gastric emptying,
-decreases glucagon
• Advantages-reduces postprandial glycemia,
-weight loss
• Disadvantages-infection,
-nausea,
-increase risk of hypoglycemia with insulin
35. Insulin
• Insulin is synthesized in the β cells of the pancreatic islets of
Langerhans as a pro-hormone (pro-insulin).
• It consisting of A- and B-chains, linked by C-peptide. C-peptide is
cleaved by β-cell peptidases to create insulin and free C-peptide.
• Insulin is an anabolic hormone (i.e. it promotes the storage of
nutrients) and has pleiotropic effects on glucose, fat and protein
metabolism.
• A key action of insulin is to lower blood glucose and, in part, this is
mediated by promoting the uptake of glucose into muscle and
adipose tissue.
36.
37. DIABETES RELATED COMPLICATIONS
• MICROVASCULAR
-EYE DISEASES-Retinopathy,
-macular edema
-NEUROPATHY-Sensory and motor(mono and polyneuropathy)
-NEPHROPATHY-(albuminuria and declining renal function)
• MACROVASCULAR
-Coronary heart disease
-Peripheral arterial disease
-Cerebrovascular disease
42. MANAGEMENT OF DIABETIC KETOACIDOSIS
• Confirm diagnosis(increased serum glucose,increased serum beta-
hydroxybutyrate,metabolic acidosis)
• Admit to hospital,intensive care setting may be necessary for
frequent monitoring,if ph<7.00.
• Assess-
-serum electrolytes(k+,Na+,Mg++,Cl-,bicarbonate,phosphate)
-Acid base status-ph,HCO3-,PCO2,beta hydroxybutyrate
-Renal function(creatinine,urine output)
43. • REPLACE FLUIDS;2-3L of 0.9% Saline or Ringer lactate over first 1-
3h(10-20ml/kg per hour).
• subsequently,0.45%Saline at 250-500ml/h,change to 5% glucose and
0.45% Saline or RL at 150-250ml/hr.
• Regular insulin infusion .
• Correction of potassium .
• Correction of bicarbonate if acidosis not reversed.
