• Normal level: 3.5–8.0 mmol/L (63–144 mg/dL)
• Liver absorbs/stores glucose in the postabsorptive state and releases it
into the circulation between meals to match the rate of glucose
utilization by peripheral tissues.
• Liver combines 3-carbon molecules derived from breakdown of fat,
muscle glycogen (lactate) and protein into the 6-carbon glucose
molecule by the process of gluconeogenesis.
• Insulin is involved in storage of glycogen in liver and muscle, and
triglyceride in fat.
• During meal: insulin is released from pancreas into the portal vein and
facilitates glucose uptake by fat and muscle and suppresses glucose
production by the liver.
• Fasting state: insulin are low and modulates glucose production from
• Counter-regulatory hormones: glucagon, adrenaline, cortisol and GH:
opposes insulin and cause production of glucose from the liver and less
utilization of glucose in fat and muscle for a given plasma level of
Type 1 diabetes mellitus:
• due to an autoimmune destruction of the pancreatic β
• occurs in genetically susceptible individuals and is
triggered by environmental antigens
• Autoantibodies against insulin and islet cell antigens
(e.g. glutamic acid decarboxylase) predate the onset of
clinical disease by several years.
• It is an association with other organ-specific
autoimmune diseases (autoimmune thyroid disease,
Addison’s disease and pernicious anaemia)
Type 2 DM
• genetic causes of type 2 DM include:
>mutations of the insulin receptor
> structural alterations of the insulin molecule
• Environmental factors: central obesity: trigger
DM in susceptible individuals
• β-cell mass is reduced to 50% at time of DX
• Hyperglycemia: result of reduced insulin
secretion and peripheral insulin resistance
• Young pt: 2– 6week hx: thirst, polyuria and wt loss
• Polyuria is due to osmotic diuresis, blood glucose exceed
renal tubular reabsorptive capacity
• Fluid and electrolyte losses stimulate thirst.
• Wt loss is due to fluid depletion and breakdown of fat and
muscle secondary to insulin deficiency.
• Ketoacidosis: if early sx are not recognized and treated.
• Older patients may present with the same symptoms,
although less marked and extending over several months.
• may also complain of lack of energy, visual problems and
pruritus vulvae or balanitis due to Candida infection.
if any one of the following is present:
• Casual plasma glucose ≥11.1 mmol/l
• Fasting plasma glucose ≥7.0 mmol/l
• 2-hour postprandial plasma glucose ≥11.1
• Metformin is a biguanide
• it reduces glucose production by the liver and
sensitizes target tissues to insulin.
• It is the first line treatment in patients who
have not achieved optimal glucose control
with diet alone, in overweight patients
• It reduces cardiovascular risk in diabetics.
• Metformin: can be used in combination tx
when single agent has failed to control DM
• anorexia and diarrhoea
• Lactic acidosis in pts with severe heart failure,
liver disease or renal disease (serum
creatinine > 150 μmol/L), in whom its use is
Sulphonylureas: promote insulin secretion.
• Glibenclamide is best avoided in elderly people
and in those with renal failure because of its
relatively long duration of action (12–20 hours)
and renal excretion.
• Tolbutamide, which is shorter acting and
metabolized by the liver, is a better choice in
• The most common side-effect of sulphonylureas
is hypoglycaemia, which may be prolonged.
• Meglitinides, e.g. repaglinide and nateglinide, are
also insulin secretagogues.
• They have a rapid onset of action and short
duration of action and are administered shortly
before each main meal.
Acarbose: inhibits intestinal α-glucosidases and
impairs carbohydrate digestion and slows
• Postprandial glucose peaks are reduced.
• Gastrointestinal side-effects, e.g. flatulence,
bloating and diarrhoea, are common and limit
the dose and acceptability of this treatment.
• Weight loss is associated with improved diabetic
control and even remission of diabetes.
• Orlistat is an intestinal lipase inhibitor and
reduces the absorption of fat from the diet.
• It promotes weight loss in patients under careful
dietary supervision on a low fat diet.
• Gastric banding and gastric bypass surgery should
be offered to those with marked obesity
unresponsive to 6 months intensive attempts at
dieting and graded exercise.
main types of insulin:
1. Short-acting (soluble) insulins:
• start working within 30–60 minutes andlast for 4–6 hours.
• They are given 15–30 minutes before meals in patients on
multiple dose regimens
2. Short-acting insulin analogues
• human insulin analogues (insulin aspart, insulin lispro,
insulin glulisine) have a faster onset and shorter duration of
action than soluble insulin but overall do not improve
• They have a reduced carry-over effect compared to soluble
insulin and are used with the evening meal in patients who
are prone to nocturnal hypoglycaemia.
3. Longer-acting insulins.
• Insulins premixed with retarding agents (either
protamine or zinc) precipitate crystals of varying size
according to the conditions employed
• These insulins are intermediate (12–24 hours) or long
acting (more than 24 hours).
• The protamine insulins are also known as isophane or
• zinc insulins as lente insulins
• Insulin glargine is a structurally modified insulin that
precipitates in tissues and is then slowly released from
the injection site.
• Thank you google…
• WHO guideline