Pharmacotherapy of Diabetes Mellitus
PST 06106
Basic Pharmacotherapy
Session 22: Pharmacotherapy of Diabetes Mellitus
Learning Objectives
By the end of this session students are expected to be able to:
Define diabetes mellitus
Explain pathophysiology of diabetes mellitus
Explain the clinical presentation of diabetes mellitus
Outline diagnosis of diabetes mellitus
Describe pharmacological treatment of diabetes mellitus
Describe the monitoring of diabetes mellitus therapy
Activity: Buzzing
What is Diabetes
Mellitus ?
Definition of Diabetes Mellitus
Diabetes mellitus (DM) is a group of metabolic disorders of fat, carbohydrate, and protein metabolism characterized by hyperglycemia
that results from defects in insulin secretion, insulin action (sensitivity), or both.
Or
Diabetes mellitus is a chronic disease caused by inherited and/or acquired deficiency in production of insulin by the pancreas, or by the ineffectiveness of the insulin produced which results in increased concentrations of glucose in the blood, which in turn damage many of the body's systems, in particular the blood vessels and nerves.
Definition of Diabetes Mellitus
Cont.…..
There are two types of DM
Type 1
diabetes (formerly known as insulin-dependent) in which the pancreas fails to produce the insulin which is essential for survival. This form develops most frequently in children and adolescents, but is being increasingly noted later in life.
Type 2
diabetes (formerly named non-insulin-dependent) which results from the body's inability to respond properly to the action of insulin produced by the pancreas.
Definition of Diabetes Mellitus Cont.…..
Type 2 diabetes is much more common and accounts for around 90% of all diabetes cases worldwide.
It occurs most frequently in adults, but is being noted increasingly in adolescents as well.
Certain genetic markers have been shown to increase the risk of developing Type 1 diabetes.
Type 2 diabetes is strongly familial, but it is only recently that some genes have been consistently associated with increased risk for Type 2 diabetes in certain populations.
Definition of Diabetes Mellitus Cont.…..
Both types of diabetes are complex diseases caused by mutations in more than one gene, as well as by environmental factors.
DM if not well managed can result into complications including;
Microvascular complications such as retinopathy, neuropathy, and nephropathy
Macrovascular
complications such as coronary heart disease, stroke, and peripheral vascular disease.
Definition of Diabetes Mellitus Cont.…..
Gestational Diabetes
It is a condition in which a woman without
diabetes
develops
high
blood sugar
levels
during
pregnancy
Diabetes in pregnancy may give rise to several adverse outcomes, including congenital malformations, increased birth weight and an elevated risk of perinatal mortality.
Strict metabolic control may reduce these risks to the level of those of non-diabetic expectant mothers
Pathophysiology Of Diabetes Mellitus
Type 1 DM
Type 1 DM is the result of a combination of genetic and environmental influences.
Type 1 DM is characterized by an absolute deficiency of pancreatic
β
-cell function.
Most often this is the result of an
immune mediated
destruction of pancreatic
β
cells, but rare unknown or idiopathic processes may contribute.
It most commonly results from autoimmune destruction of insulin-producing β-cells in the pancreas.
Pathophysiology Of Diabetes Mellitus Cont.….
One or more environmental factors, such as enteroviruses, dietary factors or toxins, might trigger the development of T-cell dependent autoimmunity in genetically susceptible individuals
Autoimmunity is manifested by detectable antibodies to ICA512/IA-2, insulin autoantibody (IAA) and glutamic acid decarboxylase (GAD).
Insulitis with gradual β-cell destruction leads to pre-diabetes and finally to overt DM.
Pathophysiology Of Diabetes Mellitus Cont.….
Type 2 DM
Type 2 diabetic individuals are characterized by
defects in insulin secretion; and
Insulin resistance involving muscle, liver, and the adipocyte.
Impaired insulin secretion
Impaired insulin secretion is a decrease in glucose responsiveness, which is observed before the clinical onset of disease.
More specifically, impaired glucose tolerance (IGT) is induced by a decrease in glucose-responsive early-phase insulin secretion, and a decrease in additional insulin secretion after meals causes postprandial
hyperglycaemia
Pathophysiology Of Diabetes Mellitus Cont.….
In the type 2 diabetic patient, decreased postprandial insulin secretion is due to both impaired pancreatic beta cell function and a reduced stimulus for insulin secretion from gut
hormones
Normally
there is an increased insulin secretion in response to an oral glucose stimulus and which is referred to as “the incretin effect”
The incretin effect is the result that gut-derived hormones (,glucagon-like peptide 1 (GLP-1) and glucose-dependent
insulinotropic
polypeptide (GIP)) when stimulated by glucose.
In type 2 diabetic patients, this “incretin effect” is very minimal
Pathophysiology Of Diabetes Mellitus Cont.….
The two gut hormones, glucagon-like peptide 1 (GLP-1) and glucose-dependent insulin tropic polypeptide (GIP), are responsible for over 90% of the increased insulin secretion seen in response to an oral glucose load.
Patients with type 2 diabetes remain sensitive to GLP-1 while they are often resistant to GIP.
Pathophysiology Of Diabetes Mellitus Cont.….
Insulin resistance
Insulin resistance is a condition in which insulin in the body does not exert sufficient action proportional to its blood concentration.
The impairment of insulin action in major target organs such as liver and muscles is a common pathophysiological feature of type 2 diabetes.
Insulin resistance develops and expands prior to disease onset.
Pathophysiology Of Diabetes Mellitus Cont.….
Insulin resistance is related to genetic factors and environmental factors (hyperglycaemia, free fatty acids, inflammatory mechanism, etc.).
Known genetic factors, such as change in the shape of insulin receptors that directly affect insulin signalling mechanisms is associated with visceral obesity and promote insulin resistance.
Glucolipotoxicity and inflammatory mediators are also important as the mechanisms for impaired insulin secretion and insulin signalling impairment
Clinical Presentation Of Diabetes Mellitus
The clinical presentations of type 1 DM and type 2 DM are very different.
Autoimmune type 1 DM can occur at any age.
Individuals with type 1 DM are often thin and are prone to develop diabetic ketoacidosis if insulin is withheld, or under conditions of severe
stress;-
P
olyuria,(Excessive urination)
P
olydipsia
,
(Excessive thirst)
P
olyphagia (Excessive eating)
Weight loss.
Blurred vision
Slow-healing sores
Frequent infections
Clinical Presentation Of Diabetes Mellitus
Signs And Symptoms Of Type 2
Diabetes
Patients
with type 2 DM often present without symptoms,
Even though complications tell us that they may have been hyperglycemic
For several years.
Often these patients are diagnosed secondary to unrelated blood testing.
Lethargy,
polyuria,
nocturnal,
and
polydipsia
Blurred vision
Slow-healing sores
Frequent infections
Patients can have normal to grossly abnormal insulin
sensitivity.
Clinical Presentation of DM
Diagnosis Of Diabetes Mellitus
DM is diagnosed by both
clinical using
signs and symptoms together with blood tests
The following are blood test for diagnosis of
DM
Glycated hemoglobin (A1C) test.
This blood test, which doesn't require fasting, indicates your average blood sugar level for the past two to three months.
It measures the percentage of blood sugar attached to hemoglobin, the oxygen-carrying protein in red blood cells.
An A1C level of 6.5 percent or higher on two separate tests indicates DM.
An A1C between 5.7 and 6.4 percent indicates prediabetes.
Below 5.7 is considered normal
.
Diagnosis Of Diabetes
Mellitus
Cont
….
Random blood glucose test.
A blood sample will be taken at a random time.
Normal blood glucose is 11
millimoles
Reading of 11.1
millimoles
per liter (
mmol
.
Fasting blood glucose test.
A blood sample will be taken after an overnight fast.
A fasting blood glucose level less than 5.6
mmol
A fasting blood glucose level from 5.6 to 6.9
mmol
A fasting blood glucose of 7
mmol
Diagnosis Of Diabetes
Mellitus
Cont
….
Oral glucose tolerance test.
For this test, fasting blood glucose level is measured after overnight fast.
Then a patient drink sugary liquid and blood glucose levels are measured periodically for the next two hours.
A blood sugar level less
than
7.8
mmol
More than 11.1
mmol
A reading between 7.8
mmol
mmol
.
Urinalysis
If type
1 diabetes
is suspected, Urinalysis will be done to investigate for the presence of ketones bodies
Diagnostic criteria for DM
Activity
: Small Group Discussion
What
is the treatment of Diabetes
Mellitus
?
Pharmacological Treatment Of Diabetes Mellitus
The primary goals of DM management are to;
reduce the risk for microvascular and macrovascular disease complications,
ameliorate symptoms,
reduce mortality,
Improve quality of life.
Near-normal
glycaemia
will reduce the risk for development of microvascular disease complications,
Pharmacological Treatment Of Diabetes
Mellitus
Cont
…
Aggressive management of traditional cardiovascular risk factors (i.e., smoking cessation, treatment of dyslipidemia, intensive blood pressure control, and antiplatelet therapy) are needed to reduce the likelihood of development of
macrovascular
disease.
Pharmacological treatment of DM depends on the type and the severity of the disease
Insulin are the mainstay for treatment of type 1 DM
Pharmacological Treatment Of Diabetes Mellitus
Cont
…
Treatment of Type 2
DM
Oral
Antihyperglycemic Drugs
Biguanide
:
Metformin
Metformin is considered the agent of first line for treatment of T2DM, in the absence of contraindications
It decreases fasting blood glucose by approximately 20% and HbA1c by 1.5%.
Pharmacological Treatment Of Diabetes Mellitus
Cont
…
Treatment of Type 2 DM
Oral Antihyperglycemic
Drugs…..
It
can be given in combination with sulfonylureas,
Glinides
, alpha-glucosidase inhibitors, insulin, thiazolidinedione (TZD), glucagon-like peptide-1 receptor agonist (RA-GLP1), dipeptidyl peptidase 4 inhibitors (iDPP4), and sodium-glucose co-transporter 2 inhibitors (iSGLT2).
Metformin
is contraindicated in patients with factors that predispose to lactic acidosis.
The predisposing factors are: A renal function damaged, concomitant liver disease or excessive alcohol intake, unstable or acute heart failure and personal history of lactic
acidosis
Pharmacological Treatment Of Diabetes Mellitus
Cont
…
Antihyperglycemic
drugs
Pharmacological Treatment Of Diabetes Mellitus
Cont
…
Antihyperglycemic drugs
Pharmacological Treatment Of Diabetes Mellitus
Cont
…
Antihyperglycemic drugs
Pharmacological Treatment Of Diabetes Mellitus
Cont
…
Antihyperglycemic drugs
Monitoring of Diabetes Mellitus Therapy
A comprehensive pharmaceutical care plan for the patient with DM is needed in order to reach treatment goals
Parameters
to monitor include
Glycemic control (tested minimally yearly; HbA
lc
<8% is good control and
HbA
lc
>9% is poor control),
Minimally, HbA
lc
should be measured twice a year in patients meeting treatment goals on a stable therapeutic regimen.
Quarterly assessments are recommended for those whose therapy has changed or who are not meeting glycemic goals.
Glycemic control requires frequent assessment and adjustment in diet, exercise, and pharmacologic
therapies
Monitoring of Diabetes Mellitus
Therapy Cont.….
L
dL
)
Fasting lipid profiles should be obtained as part of an initial assessment and thereafter at each
Follow-up visit, annually, or every 2 years if the lipid profile suggests low risk.
Documenting
regular frequency of foot exams (each visit), urine albumin assessment
(annually), dilated ophthalmologic exams (yearly or more frequently with identified abnormalities), and office visits for follow-up are also important.
Management of other cardiovascular risks (e.g., smoking and antiplatelet therapy) are components of preventive medicine strategies
Key
Points
Diabetes
mellitus (DM) is a group of metabolic disorders of fat, carbohydrate, and protein metabolism
characterized by hyperglycemia
that results from defects in insulin secretion, insulin action (sensitivity), or both
Symptoms of Diabetes Mellitus are variable and depends on the type of the disease
wheather
is type 1 or 2 DM.
Insulin is the mainstay pharmacological treatment for type 1 DM while Metformin is first line pharmacological treatment for type 2 DM obese patient
Evaluation
What
is Diabetes Mellitus?
What is the pathophysiology of Diabetes Mellitus?
What are the signs and symptoms of Diabetes Mellitus?
How is the treatment of Diabetes Mellitus?
References
Wells
BG,
DiPiro
J,
Schwinghammer
T (2013),
Pharmacotherapy Handbook
(6
th
Ed). New York, NY: McGraw-Hill.
DiPiro
JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey ML, (2008):
Pharmacotherapy: A Pathophysiologic Approach
(7
th
ed
): New York, NY: McGraw-Hill.
Katz M D., Matthias KR., Chisholm-Burns M A., Pharmacotherapy(2011)
Principles & Practice Study Guide: A Case-Based Care Plan Approach
: New York, NY: McGraw-Hill.
Schwinghammer
TL, Koehler JM (2009)
Pharmacotherapy Casebook: A Patient-Focused Approach
(7
th
ed
): New York, NY: McGraw-Hill.
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