Insulin, Glucagon and Oral

Hypoglycaemic Agents
Control of blood glucose
PANCREAS & ITS
ENDOCRINE ROLE

• It functions as both an exocrine as well as an

endocrine gland
• Located in the curve of the duodenum.
• Roughly 99% of the pancreatic cells are arranged in
clusters called acini that produce digestive enzymes,
• Scattered among the acini are the 1-2 million tine
cluster of endocrine tissue called pancreatic islets or
islets of Langerhans .
Microscopic picture of islet of Langerhans

An inflammation of body tissue (especially that below the

skin) characterized by fever and swelling and redness
and pain
Hormones secreted by pancreas
• Each islet contains 4 types of hormone producing
cells.
 α or A cells – Secrete GLUCAGON
 β or B cells – Secrete INSULIN
 δ or D cells – Secrete SOMATOSTATIN
 F cells – Remainder of the pancreatic islet cells & secrete
PANCREATIC POLYPEPTIDE
• Glucagon elevates the blood glucose levels
• Insulin lowers the blood glucose level
• Somatostatin acts in a paracrine manner to inhibit
both insulin and glucagon release from neighboring
beta and alpha cells.
• Pancreatic polypeptide somatostatin secretion
Regulation of glucagon & insulin secretion

Hypoglycemia glucagon secretion

Hyperglycemia (Glucose Glycogen)

. Glucagon & Insulin secretion

. Entry of glucose into cells especially skeletal

muscle & its utilization; speed Glycogenesis in the
liver
. Increase cellular uptake of amino acids & protein
synthesis
. Speed Lipogenesis , Gluconeogenesis &
glycogenolysis
 Other stimuli that cause insulin release

• hGH (Human growth hormone)

• ACTH
• Acetylcholine
• Arginine& Leucine (amino acids in meals)
• Adrenaline
Factors regulating insulin secretion
Diabetes Mellitus
Diabetes Mellitus is a chronic metabolic disorder
characterized by hyperglycemia due to an absolute
or relative lack of insulin or to a cellular resistance
to insulin
Hyperglycemia :-
• There is an inability of a cell to oxidize carbohydrates
due to disturbance in insulin secretion/function.
• High blood glucose concentration (fasting plasma
glucose > 7.0 mmol/l (126mg/dl), or plasma glucose >
11.1 mmol/l (200mg/dl), 2 hours after a meal)
 Diabetes Mellitus
Diabetes is any disorder characterized by :-

• excessive urine secretion

• hyperglycemia,
• glucosuria,
• ketosis,
• ketonuria,
• Polyuria
• Polydypsia (excessive thirst)
• Polyphagia (excessive hunger)
• Muscle wasting
 Diabetes Mellitus
Impact on health of population
• Sixth leading cause of death due to cardiovascular effects
resulting in atherosclerosis, coronary artery disease, and
stroke
• Leading cause of end stage renal failure
• Major cause of blindness
• Most frequent cause of non-traumatic amputations
• Diabetes affects estimated 15.7 million people (10.3 million
are diagnosed; 5.4 million are undiagnosed)
• Increasing prevalence of Type 2 Diabetes in older adults and
minority groups (African American, American Indian and
Hispanic populations)
Type of Diabetes Mellitus
• Type I Diabetes (insulin-dependent diabetes
mellitus, IDDM)
– characterized by severe insulinopenia and
dependence on exogenous insulin to prevent
ketosis and to preserve life
– onset occurs predominantly in childhood
– probably has some genetic predisposition and is
likely autoimmune-mediated
• Type II Diabetes (non-insulin-dependent
diabetes mellitus, NIDDM)
– patients are not insulin dependent and rarely
develop ketosis
Type of Diabetes Mellitus
– generally occurs after age 40, and there is a high
incidence of associated obesity
– insulin secretion generally adequate; insulin
resistance is present
– no associated genetic predisposition
• Secondary Diabetes
– occurs in response to other disease processes:
• exocrine pancreatic disease (cystic fibrosis)
• Cushing syndrome
• poison ingestion (rodenticides)
Type I Diabetes Mellitus
• Metabolic condition in which the beta cells of
pancreas no longer produce insulin; characterized
by hyperglycemia, breakdown of body fats and
protein and development of ketosis
• Accounts for 5 – 10 % of cases of diabetes; most
often occurs in childhood or adolescence
• Formerly called Juvenile-onset diabetes or insulin-
dependent diabetes (IDDM)

Pathophysiology
• Autoimmune reaction in which the beta cells that
produce insulin are destroyed
• Alpha cells produce excess glucagons causing
hyperglycemia
Type I Diabetes Mellitus
Risk Factors
• Genetic predisposition for increased susceptibility
• Environmental triggers stimulate an autoimmune
response
• Viral infections (mumps, rubella, coxsackievirus B4)
• Chemical toxins
Manifestations
• Process of beta cell destruction occurs slowly;
hyperglycemia occurs when 80 – 90% is destroyed;
often trigger stressor event (e. g. illness)
Type I Diabetes Mellitus
• Hyperglycemia leads to

 Polyuria (hyperglycemia acts as osmotic diuretic)

 Glycosuria (renal threshold for glucose: 180 mg/dL)
 Polydipsia (thirst from dehydration from polyuria)
 Polyphagia (hunger and eats more since cell cannot
utilize glucose)
 Weight loss (body breaking down fat and protein to
restore energy source
 Malaise and fatigue (from decrease in energy)
 Blurred vision (swelling of lenses from osmotic
effects)
 Type I Diabetes Mellitus
Diabetic Ketoacidosis (DKA)

• Results from breakdown of fat and

overproduction of ketones by the liver and loss
of bicarbonate
• Occurs when Diabetes Type 1 is undiagnosed or
known diabetic has increased energy needs,
when under physical or emotional stress or fails
to take insulin :- Mortality as high as 14%
• Pathophysiology
 Hypersomolarity (hyperglycemia, dehydration)
 Metabolic acidosis (accumulation of ketones)
 Fluid and electrolyte imbalance (from osmotic
diuresis)
Type I Diabetes Mellitus
Diagnosis
• Patient is symptomatic plus
• Casual plasma glucose (non-fasting) is 200 mg/dl OR
• Fasting plasma glucose of 126 mg/dl or higher OR
• Two hour plasma glucose level of 200 mg/dl or greater
during an oral glucose tolerance test
Diagnostic tests
• Blood glucose greater than 250 mg/dL
• Blood pH less than 7.3
• Blood bicarbonate less than 15 mEq/L
• Ketones present in blood
• Ketones and glucose present in urine
• Electrolyte abnormalities (Na, K, Cl)
• Serum osmolality < 350 mosm/kg (normal 280-300)
Type 2 Diabetes Mellitus
• Characterized by chronic hyperglycemia
• Condition of fasting hyperglycemia occurring
despite availability of body’s own insulin
• Generally arises from a combination of insulin
resistance and β -cell dysfunction
• Was known as non-insulin dependent diabetes or
adult onset diabetes
Pathophysiology
• Sufficient insulin production to prevent DKA; but
insufficient to lower blood glucose through uptake
of glucose by muscle and fat cells
• Cellular resistance to insulin increased by obesity,
inactivity, illness, age, some medications
Type 2 Diabetes Mellitus
What is insulin resistance?
• Major defect in individuals with type 2 diabetes
• Reduced biological response to insulin
• Strong predictor of type 2 diabetes
• Closely associated with obesity
What is β -cell dysfunction?
• Major defect in individuals with type 2 diabetes
• Reduced ability of β -cells to secrete insulin in
response to hyperglycemia
Insulin resistance and β -cell dysfunction
are core defects of type 2 diabetes

Genetic susceptibility,
obesity, Western lifestyle

Insulin
resistance IR β β -cell
dysfunction

Type 2 diabetes
Insulin resistance – reduced
response to circulating insulin

Insulin
resistance IR

Liver Muscle Adipose

tissue

↑ Glucose output ↓ Glucose uptake ↓ Glucose uptake

Hyperglycemia
Type 2 Diabetes : Complex pathophysiology
Dual defects → bipolar disease

Carbohydrate
DIGESTIVE ENZYMES
Glucose Excessive
fatty acid release
s e (G) I G
o
Gluc
I
Insulin G I
Defective Adipose
(I) G

G
β −cell secretion Tissue

I
G
Pancreas I G
G
I
I G Reduced
Liver G
I
I Glucose
Excess G
uptake
G

glucose
production
Muscle

Partial defect of insulin secretion Resistance to the action of insulin

Type 2 Diabetes Mellitus
Risk Factors

• History of diabetes in parents or siblings

• Obesity (especially of upper body)
• Physical inactivity
• Race/ethnicity: African American, Hispanic, or
American Indian origin
• Women: history of gestational diabetes,
polycystic ovary syndrome, delivered baby with
birth weight > 9 pounds
• Clients with hypertension; HDL cholesterol < 35
mg/dL, and/or triglyceride level > 250 mg/dl.
Diabetes Mellitus
• Syndrome X or Metabolic Syndrome
– Chronic, low grade inflammatory process
– Gives rise to diabetes type 2, ischemic heart
disease, left ventricular hypertrophy
– Group of disorders with insulin resistance as
the main feature
– Includes
• Obesity especially around the waist and abdomen
• Low levels of physical activity
• High blood pressure
• Increased blood cholesterol (high LDL, low HDL, high
triglycerides
More than 80% of patients progressing to
type 2 diabetes are insulin resistant
Insulin sensitive;
low insulin secretion
(16%)

Insulin resistant;
Insulin low insulin secretion
sensitive; (54%)
good insulin
secretion (1%)

Insulin resistant;
good insulin secretion
(29%)
Diabetes Mellitus
Manifestations
1. Client usually unaware of diabetes
• Discovers diabetes when seeking health care for another
concern
• Most cases aren’t diagnosed for 5-6 years after the
development of the disease
• Usually does not experience weight loss
2. Possible symptoms or concerns
• Hyperglycemia (not as severe as with Type 1)
• Polyuria
• Polydipsia
• Blurred vision
• Fatigue
• Paresthesias (numbness in extremities)
• Skin Infections
Diabetes Mellitus
3.Specific manifestations
• Cool, clammy skin
• Rapid heartbeat
• Hunger
• Nervousness, tremor
• Faintness, dizziness
• Unsteady gait, slurred and/or incoherent speech
• Vision changes
• Seizures, coma
• Severe hypoglycemia can result in death
• Clients taking medications, such as beta-adrenergic
blockers may not experience manifestations associated
with autonomic nervous system
• Hypoglycemia unawareness: clients with Diabetes Type 1
for 4 or 5 years or more may develop severe hypoglycemia
without symptoms which can delay treatment
Diabetes Mellitus
Complications of Diabetes
A. Alterations in blood sugars: hyperglycemia and
hypoglycemia
B. Macrocirculation (large blood vessels)
• Atherosclerosis occurs more frequently, earlier in
diabetics
• Involves coronary, peripheral, and cerebral arteries
C. Microcirculation (small blood vessels)
• Affects basement membrane of small blood vessels
and capillaries
• Involves tissues affecting eyes and kidneys
D. Prevention of complications
• Managing diabetes
• Lowering risk factors for conditions
• Routine screening for complications
• Implementing early treatment
Diabetes Mellitus
Complications Affecting Cardiovascular
System, Vision, and Kidney Function
A. Coronary Artery Disease
1. Major risk of myocardial infarction in Type 2 diabetics
Increased chance of having a silent MI and delaying
medical treatment
2. Most common cause of death for diabetics (40 – 60%)
3. Diabetics more likely to develop Congestive Heart
Failure
B. Hypertension
1. Affects 20 – 60 % of all diabetics
2. Increases risk for retinopathy, nephropathy
Diabetes Mellitus
C. Stroke:
• Type 2 diabetics are 2 – 6 times more likely to
have stroke as well as Transient Ischemic
Attacks (TIA) or mini stroke

D. Peripheral Vascular Disease

1. Increased risk for Types 1 and 2 diabetics
2. Development of arterial occlusion and thrombosis
resulting in gangrene
3. Gangrene from diabetes most common cause of
non-traumatic lower limb amputation
Diabetes Mellitus
Diabetic Retinopathy
 Retinal changes related to diabetes
Hemorrhage, swelling, decreased vision
 Leads to retinal ischemia and breakdown of blood-
retinal barrier
 Leading cause of blindness ages 25 – 74
• Affects almost all Type 1 diabetics after 20 years
• Affects 60 % of Type diabetics
 Diabetics should be screened for retinopathy and
receive treatment (laser photocoagulation surgery) to
prevent vision loss (Should be sent immediately to
ophthalmologist upon diagnosis because may already have damage)
 Diabetics also have increased risk for cataract
development
Diabetes Mellitus
Diabetic Nephropathy
• Glomerular changes in kidneys of diabetics
leading to impaired renal function
• First indicator: microalbuminuria
• Diabetics without treatment go on to develop
hypertension, edema, progressive renal
insufficiency
– In type 1 diabetics, 10 – 15 years
– May occur soon after diagnosis with type 2 diabetes since many are
undiagnosed for years
• Most common cause of end-stage renal failure in
U.S.
• Kimmelstiel-Wilson syndrome:
glomerulosclerosis associated with diabetes
Diabetes Mellitus
Other Complications from Diabetes
A. Increased susceptibility to infection
• Predisposition is combined effect of other
complications
• Normal inflammatory response is diminished
• Slower than normal healing
B. Periodontal disease
C. Foot ulcers and infections: predisposition is
combined effect of other complications
D. Male erectile dysfunction
• Half of all diabetic men have erectile dysfunction
Diabetes Mellitus
Collaborative Care
A. Based on research from 10-year study of Type 1
diabetics conducted by NIH focus is on keeping
blood glucose levels as close to normal by active
management interventions; complications were
reduced by 60%
B. Treatment interventions are maintained through
• Medications
• Dietary management
• Exercise
C. Management of diabetes with pancreatic
transplant, pancreatic cell or Beta cell transplant
is in investigative stage
 Diabetes Mellitus
Diagnostic tests to monitor diabetes management
1. Fasting Blood Glucose (normal: 70 – 110 mg/dL)
2. Glycosylated hemoglobin (c) (Hemoglobin A1C)
• Considered elevated if values above 7%
• Blood test analyzes excess glucose attached to
hemoglobin. Since RBC lives about 120 days gives
an average of the blood glucose over previous 2 to
3 months
– Not a fasting test, can be drawn any time of the day
– % of glycated (glucose attached) hemoglobin measures
how much glucose has been in the bloodstream for the
past 3 months
)
 Diabetes Mellitus
3. Urine glucose and ketone levels (part of routine
urinalysis)
• Glucose in urine indicates hyperglycemia (renal threshold is
usually 180 mg/dL)
• Presence of ketones indicates fat breakdown, indicator of
DKA; ketones may be present if person not eating
4. Urine albumin (part of routine urinalysis)
• If albumin present, indicates need for workup for nephropathy
• Typical order is creatinine clearance testing
5. Cholesterol and Triglyceride levels
• LDL < 100 mg/dl, HDL > 45 mg/dL, TG < 150 mg/dL
• Monitor risk for atherosclerosis and CVS complications
6. Serum electrolytes in clients with DKA or HHNS
Treatment of Diabetes Mellitus
1. Non-medicine treatment
• Regular mild to moderate exercise
• Controlled diet
2. Treatment of IDDM
• Insulin replacement therapy (a must)
• Insulin + Oral hypoglycemic agents (sometimes)
3. Treatment of NIDDM
• Oral hypoglycemic agents
Treatment of Diabetes Mellitus
Medications - Insulin
Clients who need insulin as therapy:
• All type 1 diabetics since their bodies essentially no
longer produce insulin
• Some Type 2 diabetics, if oral medications are not
adequate for control (both oral medications and
insulin may be needed)
• Diabetics enduring stressor situations such as
surgery, corticosteroid therapy, infections, treatment
for DKA
• Women with gestational diabetes who are not
adequately controlled with diet
• Some clients receiving high caloric feedings
including tube feedings or parenteral nutrition
 Insulin
• For there is evidence that precise control of
blood glucose , with using insulin, is imp. for
preventing the long-term complications which
are responsible for the morbidity and mortality
associated with DM.
• Insulin is assayed by using biological method
and its quantity is expressed in terms of ‘units’
• 1 Unit = Amount of insulin that is required to
reduce blood conc. of glucose in fasting rabbits
by 45 mg/dl.
• Insulin preparations, commonly available in
India, are in strengths of 40 IU/ml and 100 IU/ml
Some physiological aspects of insulin

Insulin release in response to blood glucose

Release of preformed insulin (Phase I)

Phase II
NORMAL

NIDDM

IDDM

0 15 30 45 60 75 min (Time for which glucose was infused)

 Insulin
• Insulin preparations – Bovine, Porcine, or Human
• Insulin, used clinically, is extracted from bovine or porcine
pancreatic tissue and is not identical with the human
hormone.
• Bovine insulin differs in three amino acid residues and
pork insulin in one.
• Bovine insulin preparations are most antigenic whereas
the Human insulin preparations are least.
• The use of techniques involving chain recombinant DNA
in bacteria is (crb) insulin and enzymatic techniques to
modify pork insulin (emp insulin).
• Crystalline, soluble insulin has rapid but short-lived
action. It can be given intravenously
• Longer-acting insulin preparations (lente, semilente,
ultralente) are insoluble and are given by s.c. route.
 Insulin
• When rapid acting or short acting insulin is mixed with
longer acting insulin, draw the short acting insulin into
the syringe first.
• Prevents contamination of the shorter acting insulin
with the longer acting insulin
• Insuling glargine (Lantus) should not be mixed with
any other insulin
• Insulin preparations should always be stored at a
temp. of 2-80 C
• Injection sites
– Abdominal areas is the most preferred because of rapid
absorption
– Do not aspirate insulin injections
– Administration covered in the lab
Insulin
Insulin - Injection Sites
 Type of Insulin
TYPE Appea- Added Buffer Action (Hours)
rance protein Onset Peak Duration
RAPID

Regular (cryst.) Clear None None 0.3-0.7 2-4 5-8

Semilente Cloudy None Acetate 0.5-1 2-8 12-16

INTERMEDIATE

NPH (Isophane) Cloudy Protam. Phosph. 1-2 6-12 18-24

Lente Cloudy None Acetate 1-2 6-12 18-24

SLOW

Ultralente Cloudy None Acetate 4-6 16-18 20-36

Protamine zinc Cloudy Protam. Phosph. 4-6 14-20 24-36

Insulin
• Alternative insulin administration
– Insulin pump
• Continuous subcutaneous
infusion of a basal dose
with increases at meal times
– Implanted pumps
• Implanted into the peritoneal cavity
– Inhaled insulin
• Under development
MECHANISM OF ACTION OF INSULIN

Insulin binding to its receptors located on the surface

of its target cell

Aggregation of insulin-occupied receptors

Endocytosis of insulin

Intracellular actions of insulin

Insulin signalling pathways
Summary of insulin effects on metabolism

Liver cells Fat cells Muscle

Carbohydrate gluconeogenesis glucose uptake glucose uptake

metabolism
glycogenolysis glycerol synth. glycolysis

glycolysis glycogenesis

glycogenesis

Fat metabol. lipogenesis synth. of TGs.

fatty acid syth.
Prot. Metabol. prot. Breakdown __ am. acid uptake
prot. Synth.
Overview of insulin action
Fatty Glucose Amino
acids acids

TGs Glycogen Protein

Adipose Liver Muscle
tissue

Fatty acids
 Clinical uses of insulin
• Patients with type 1 diabetes require long-term insulin:
– an intermediate-acting preparation (e.g. isophane insulin) is often
combined with soluble insulin taken before meals.
• Soluble insulin is used (intravenously) in emergency treatment of
hyperglycaemic emergencies (e.g. diabetic ketoacidosis).
• Many patients with type 2 diabetes ultimately need insulin.
• Short-term treatment of patients with type 2 diabetes or impaired
glucose tolerance during intercurrent events (e.g. operations,
infections, myocardial infarction).
• During pregnancy, for gestational diabetes not controlled by diet
alone.
• Emergency treatment of hyperkalaemia: insulin is given with
glucose to lower extracellular K+ via redistribution into cells.
 Insulin
ADVERSE EFFECTS
• Insulin resistance (rare) due to development of insulin
antibodies
• Allergic reactions
• Insulin induced hypoglycemic shock (in case of
overdose), coma, death.
DRUG INTERACTIONS
• Drugs which decrease hypoglycemic effects of insulin
Oral contraceptives, Corticosteroids, Diltiazem, Smoking,
Thiazide diuretics.
• Drugs which increase hypoglycemic effects of insulin
Propranolol, Anabolic steroids, Salicylates
Treatment of Diabetes Mellitus
Oral Hypoglycaemic Agents
• Used to treat Diabetes Type 2
• Client must also maintain prescribed diet and
exercise program; monitor blood glucose levels
• Not used with pregnant or lactating women
• Several different oral hypoglycemic agents and
insulin may be prescribed for the client
• Specific drug interactions may affect the blood
glucose levels
• Must have some functioning beta cells
Oral Hypoglycaemic Agents
Classification of OHA
• Sulfonylureas :-
Glipizide (Glucotrol), Chlorpropamide (Diabinese),
Tolazamide (Tolinase)
• Meglitinides :-
Repaglinide (Prandin), Nateglinide (Starlix)
• Biguanides :-
Metformin (Glucophage)
• Alpha-glucoside Inhibitors :-
Acarbose (Precose), Miglitol (Glyset), Voglibose
• Thizaolidinediones (Glitazones) :-
Rosiglitazone (Avandia), Pioglitazone (Actos)
Oral Hypoglycaemic Agents
Sulfonylureas
• Sulfonylureas that stimulate insulin secretion (e.g.
tolbutamide, glibenclamide)
– can cause hypoglycaemia (which stimulates appetite and
leads to weight gain)
– are effective only if β-cells are functional
– block ATP-sensitive potassium channels in β-cells
– Stimulates pancreatic cells to secrete more insulin and
increases sensitivity of peripheral tissues to insulin
– Used: to treat non-obese Type 2 diabetics
– are well tolerated but promote weight gain
Oral Hypoglycaemic Agents
Meglitinides
• Meglitinides (Repaglinide,Nateglinide)
– Act, like the sulfonylureas, by blocking the sulfonylurea
receptor on KATP channels in pancreatic B cells and
stimulates pancreatic cells to secret more insulin.
– Much less potent than most sulfonylureas (with the
exception of tolbutamide), and has rapid onset and offset
kinetics.
– Rapid absorption (time to maximal plasma concentration
approximately 55 minutes after an oral dose) and
elimination (half-life approximately 3 hours), short duration
of actiona (low risk of hypoglycaemia)
– Taken just before meals,
– Used in non-obese diabetics
Oral Hypoglycaemic Agents
Biguanides
• Biguanides (e.g. metformin):
– have complex peripheral actions in the presence of residual
insulin, increasing glucose uptake in striated muscle and
inhibiting hepatic glucose output and intestinal glucose
absorption
– Metabolized by the kidney, do not use with renal patients
– cause anorexia and encourage weight loss
– can be combined with sulfonylureas.
– Used in obese diabetics
– Does not stimulate insulin release
Oral Hypoglycaemic Agents
Alpha-glucoside Inhibitors
• α-Glucosidase inhibitor: Acarbose, Miglitol,
Voglibose
– Reduces carbohydrate digestion and delay rate of
glucose absorption
– Take with first bite of the meal or 15 min. after
– Adjunct to diet to decrease blood glucose levels
– causes flatulence and diarrhoea
Oral Hypoglycemic Agents
Thizaolidinediones (Glitazones)
• Thiazolidinediones (e.g. rosiglitazone, pioglitazone)
– increase insulin sensitivity and lower blood glucose in type 2
diabetes
– Sensitizes peripheral tissues to insulin :- Improves sensitivity
to insulin in muscle, and fat tissue
– Inhibits glucose production
– are peroxisome proliferator-activated receptor-γ (a nuclear
receptor) agonists.
– can cause weight gain and oedema
The dual action of thiazolidinediones
reduces HbA1c

+
Insulin β -cell
resistance IR β function

HbA1c
Oral Hypoglycaemic Agents
• Patients with Type 2 DM who are obese have
insulin resistance, they produce enough
insulin
– Should use Glucophage, Actos or Avandia
– Enhances insulin secretion in tissue, but does not
increase amount of insulin secreted
• Patients with Type 2 DM who are thin do not
produce enough insulin, they are not insulin
resistant
– Need sulfonylurea agents like Diabinese, Tolinase,
Glucotrol, Diabeta
Primary sites of action of oral
hypoglycaemic agents

α -glucosidase Sulfonylureas/
inhibitors meglitinides Biguanides Thiazolidinediones

↓ Carbohydrate ↑ Insulin ↓ Glucose ↓ Insulin

breakdown/ secretion output resistance
absorption ↓ Insulin resistance
Clinical uses of oral hypoglycaemic
agents
• Type 2 diabetes mellitus, to reduce symptoms
from hyperglycemia (e.g. thirst, excessive
urination).
• Metformin is preferred for obese patients unless
contraindicated by factor(s) that predispose to
lactic acidosis (renal or liver failure, heart failure,
hypoxaemia).
• Acarbose (α-glucosidase inhibitor) reduces
carbohydrate absorption; it causes flatulence and
diarrhoea.
• Drugs that act on the sulfonylurea receptor (e.g.
tolbutamide, glibenclamide) are well tolerated but
often promote weight gain.
Treatment of Diabetes Mellitus
Role of Diet in Diabetic Management
A. Goals for diabetic therapy include
• Maintain as near-normal blood glucose levels as possible with
balance of food with medications
• Obtain optimal serum lipid levels
• Provide adequate calories to attain or maintain reasonable weight
B. Diet Composition
• Carbohydrates: 60 – 70% of daily diet
– Carbohydrates convert quickly to sugars
• Advice patient to consume a similar amount of carbs at each meal
• Medications can work on a consistent glucose response from foods
• Protein: 15 – 20% of daily diet
• Fats: No more than 10% of total calories from saturated fats
Treatment of Diabetes Mellitus
• Fiber: 20 to 35 grams/day; promotes intestinal motility and
gives feeling of fullness
• Sodium: recommended intake 1000 mg per 1000 kcal
• Sweeteners approved by FDA instead of refined sugars
• Limited use of alcohol: potential hypoglycemic effect of
insulin and oral hypoglycemics
C. Diet
• Look for more dietary information online at
http://www.diabetes.org/nutrition-and-
receipes/nutrition/overview.jsp
Treatment of Diabetes Mellitus
Care of diabetic older clients
• 40% of all clients with diabetes are over age of 65
• Need to include spouse, members of family in teaching
who may assist with client meeting medical needs
• Diet changes may be difficult to implement since client
has established eating habits
• Exercise programs may need adjustment to meet
individual’s abilities (such as physical limitations from
other chronic illnesses)
– Obesity worsens diabetes
– Minimum of 30 minutes of moderate exercise like walking or
swimming most days of the week
Treatment of Diabetes Mellitus
• Individual reluctance to accept assistance to deal
with chronic illness, assist with hygiene
• Limited assets for medications, supplies, dietary
• Visual deficits or learning challenges to learn insulin
administration, blood glucose monitoring
• Assisting clients with problem-solving strategies for
specific concerns
• Providing information about diabetic resources,
community education programs, and support groups
• Utilizing any client contact as opportunity to review
coping status and reinforce proper diabetes
management and complication prevention
Diabetes insipidus
• Chronic excretion of very large amounts of pale urine
of low specific gravity, causing dehydration and
extreme thirst
• Ordinarily results from inadequate output of pituitary
antidiuretic hormone; may be mimicked as a result of
excessive fluid intake, as in psychogenic polydipsia
• Disorder of ADH secretion, which can be
– Neurogenic : due to reduced secretion of ADH
– Nephrogenic : due to impaired response of the nephron to
ADH
• Some drugs (lithium, demeclocycline, colichcine,
vinca alkaloids) cause diabetes insipidus
Glucagon
• Glucagon is a single-chain polypeptide of 21 amino acid
residues.
• Glucagon is a fuel-mobilising hormone, stimulating
gluconeogenesis and glycogenolysis, also lipolysis and
proteolysis. It increases blood sugar and also increases
the force of contraction of the heart.
SYNTHESIS, SECRETION AND ACTION
• Glucagon is synthesised mainly in the A cell of the islets,
but also in the upper GIT. It has considerable structural
homology with other gastrointestinal tract hormones,
including secretin vasoactive intestinal peptide and GIP.
One of the main physiological stimuli to glucagon
secretion is the concentration of amino acids, in particular
L-arginine, in plasma.
Glucagon
• Sympathetic nerve activity and circulating adrenaline stimulate
glucagon release via β adrenoceptors. Parasympathetic nerve
activity also increases secretion, whereas somatostatin, released
from D cells adjacent to the glucagon-secreting A cells in the
periphery of the islets, inhibits glucagon release.
• Glucagon increases blood glucose and causes breakdown of fat
and protein. It acts on specific G-protein-coupled receptors to
stimulate adenylate cyclase, and consequently its actions are
somewhat similar to β adrenoceptor-mediated actions of
adrenaline.
• Glucagon stimulates glycogen breakdown and gluconeogenesis,
and inhibits glycogen synthesis and glucose oxidation.
Clinical uses of glucagon
• Glucagon can be given intramuscularly or subcutaneously as
well as intravenously.
• Treatment of hypoglycaemia in unconscious patients (who
cannot drink); unlike intravenous glucose, it can be
administered by non-medical personnel (e.g. spouses or
ambulance crew). It is useful if obtaining intravenous access is
difficult.
• Treatment of acute cardiac failure precipitated by β-
adrenoceptor antagonists.
• Metabolic actions of glucogen on target tissues are thus the
opposite of those of insulin. Glucagon increases the rate and
force of contraction of the heart, although less markedly than
adrenaline.