10/9/24, 11:40 Diabete
AM s
Diabetes Mellitus (Part 1)
Diabetes - excessive secretion of urine
Diabetes Mellitus - refers to the disorder of carbohydrates, fat, and protein metabolism with
absolute or relative insulin deficiency
Note: Frequent urination, increased thirst, increased hunger
● Beta cells - store and release insulin (reduces blood glucose)
● Ketoacidosis - develops when body is unable to produce enough insulin so body
breaks down fat for fuel = buildup of ketones in bloodstream.
Etiology Type 1 DM
Type 1 is categorized into 2 types:
1. Autoimmune Type 1A
a. Accounts for 90-95% of type 1 DM cases
b. Specific loss of beta cells in the pancreatic islets of Langerhans
c. Includes cases of diabetes that are primarily the result of beta cells
destruction which leads to absolute insulin deficiency and is prone to
ketoacidosis
d. Result of the genetic-environment interaction
e. Genes:
i. MHC (major histocompatibility complex) genes on Chromosome 6
which encode for human leukocyte antigen HLA-DQ and HLA-DR
ii. In particular, HLA-DR3 and HLA-DR4 is associated with an increased
risk of Type 1A diabetes that is 20-40 times higher than that of the general
population
iii. HLA-DR2 - human leukocytes that are thought to decrease the risk
of developing Type 1 diabetes
iv. Chromosome 11 - insulin gene regulating beta cell replication and
function
f. In most cases, there is likely a polygenic inheritance of Type 1 diabetes -
meaning that susceptible individuals have more than one genetic
polymorphism. (occurs when one characteristic is controlled by two or more
genes)
i. More than one gene that codes for T1 DM
g. Between 10 and 13% individuals with newly diagnosed Type 1 diabetes have
a first-degree relative with type 1 diabetes
h. Autoantibodies (produced by immune system directed against one or more of the
individual’s own proteins; attacks self-antigens): specific to beta cell destruction
include;
i. Insulin autobodies
ii. Islet cell autoantibodies
iii. Antibodies directed at other islet autoantigens (such as glutamic
acid decarboxylases - GAD and tyrosine phosphatase IA-2)
i. Environmental factors such as drugs and chemicals interact with genes too
about:blan 1/
k 17
,10/9/24, 11:41 Diabete
AM s
j. Chemicals and Alloxan, streptozotocin and vacor as well as certain drugs such
as Pentamidine have been associated with type 1 diabetes
k. Nutritional intake of Bovine milk and high levels of nitrosamines has also been
linked to type 1 diabetes
l. Virus: 40% of individuals with congenital rubella infection develop diabetes
type 1 later, persistent cytomegalovirus infection appear relevant in some cases
of type 1 diabetes
m. There is a small number of adults (~10%) classifies as having type 2 who appear
to have immune mediated destruction of beta cells who actually fall into the
category of type 1A diabetes
i. It is called “latent autoimmune disease in adult” or LADA - otherwise,
type 1 diabetes is diagnosed in childhood for the most part
ii. Diagnosis peaks at 12 years of age and is rare before 9 months of age
2. Idiopathic Type 1B/Non-immune Type 1 Diabetes
a. No evidence of autoimmunity; the etiology is unknown
b. Accounts for <10% of those with type 1 diabetes
c. Strong genetic component to the development of type 1B diabetes
d. Most affected individuals are of African or Asian descent
e. Varying levels of insulin deficiency - episodic ketoacidosis
f. Affected individuals have varying degrees of insulin deficiency that can come
and go which leads to varying degrees of insulin deficiency that can come and
go which leads to episodic ketoacidosis
Etiology Type 2 DM
● Type 2 diabetes is a heterogeneous condition characterized by hyperglycemia,
insulin resistance and relative impairment in insulin secretion
● Range from predominant insulin resistance with relative insulin deficiency to
a predominant secretory defect with insulin resistance
● It is an environment-genetic interaction - 12-25% will develop either impaired glucose
tolerance or diabetes
● Variants of genes have been identified that increase the risk for Type 2 Diabetes:
○ Genetic defects of beta cell function
○ Genetic defects in insulin synthesis, secretion and action
○ Genes that encode proteins for pancreatic development
○ Amyloid deposition in beta cells
○ Cellular insulin resistance and impaired regulation of gluconeogenesis
● Risk factor for type 2 diabetes:
○ Age
○ Obesity
○ Hypertension
○ Physical inactivity
○ Family hx
○ Metabolic syndrome - high risk of developing type 2 diabetes with
cardiovascular complications
● Type 2 DM occurs mostly in adults
○ Canadian aboriginal children are particularly affected
about:blan 2/
k 17
, 10/9/24, 11:41 Diabete
AM s
Etiology GDM (Gestational) and Other
Gestational Diabetes Mellitus
● Any degree of glucose intolerance with onset or first recognition during pregnancy
● Pregestational diabetes - pregnancy in persons with pre-existing diabetes
● Combination of insulin resistance and impaired insulin secretion are most
definitely contributing factors
● Risk factors:
○ Older age
○ Family hx
○ Hx of glucose intolerance
○ Obesity
○ Membership in certain ethnic/racial group
○ Hx of poor obstetric outcomes and infant weighing greater than 9lbs
● Diagnosis is made based on the gestational diabetes screen which is a 50g glucose
load followed by a plasma glucose level 1h later
● Diagnosis of gestational diabetes is made based on different lab values
● Untreated gestational diabetes leads to increased maternal and perinatal morbidity
Other:
● Specific genetically defined forms of diabetes include: genetic defects of beta
cell function and genetic defects in insulin action
● MODY (Maturity Onset Diabetes of the Young) - specific grouping of
genetically defined form of diabetes
○ Individuals present at a young age have mild disease due to beta cell dysfunction
with some insulin production and inherit the disease via autosomal dominant
transmission
○ There is normal insulin sensitivity in individuals with MODY
○ These genetic abnormalities are not often referred to their specific description,
for example: MODY 2 excompasses over a dozen mutations in the glucokinase
on chromosome 7
Note:
● Beta cell dysfunction
● Some insulin production
● Normal insulin sensitivity
● Autosomal-dominant inheritance - genetic inheritance pattern where an abnormal
gene (inherited from one parent) is dominant over the normal gene (inherited
from another parent)
○ Individual characteristics associated with abnormal gene
about:blan 3/
k 17
AM s
Diabetes Mellitus (Part 1)
Diabetes - excessive secretion of urine
Diabetes Mellitus - refers to the disorder of carbohydrates, fat, and protein metabolism with
absolute or relative insulin deficiency
Note: Frequent urination, increased thirst, increased hunger
● Beta cells - store and release insulin (reduces blood glucose)
● Ketoacidosis - develops when body is unable to produce enough insulin so body
breaks down fat for fuel = buildup of ketones in bloodstream.
Etiology Type 1 DM
Type 1 is categorized into 2 types:
1. Autoimmune Type 1A
a. Accounts for 90-95% of type 1 DM cases
b. Specific loss of beta cells in the pancreatic islets of Langerhans
c. Includes cases of diabetes that are primarily the result of beta cells
destruction which leads to absolute insulin deficiency and is prone to
ketoacidosis
d. Result of the genetic-environment interaction
e. Genes:
i. MHC (major histocompatibility complex) genes on Chromosome 6
which encode for human leukocyte antigen HLA-DQ and HLA-DR
ii. In particular, HLA-DR3 and HLA-DR4 is associated with an increased
risk of Type 1A diabetes that is 20-40 times higher than that of the general
population
iii. HLA-DR2 - human leukocytes that are thought to decrease the risk
of developing Type 1 diabetes
iv. Chromosome 11 - insulin gene regulating beta cell replication and
function
f. In most cases, there is likely a polygenic inheritance of Type 1 diabetes -
meaning that susceptible individuals have more than one genetic
polymorphism. (occurs when one characteristic is controlled by two or more
genes)
i. More than one gene that codes for T1 DM
g. Between 10 and 13% individuals with newly diagnosed Type 1 diabetes have
a first-degree relative with type 1 diabetes
h. Autoantibodies (produced by immune system directed against one or more of the
individual’s own proteins; attacks self-antigens): specific to beta cell destruction
include;
i. Insulin autobodies
ii. Islet cell autoantibodies
iii. Antibodies directed at other islet autoantigens (such as glutamic
acid decarboxylases - GAD and tyrosine phosphatase IA-2)
i. Environmental factors such as drugs and chemicals interact with genes too
about:blan 1/
k 17
,10/9/24, 11:41 Diabete
AM s
j. Chemicals and Alloxan, streptozotocin and vacor as well as certain drugs such
as Pentamidine have been associated with type 1 diabetes
k. Nutritional intake of Bovine milk and high levels of nitrosamines has also been
linked to type 1 diabetes
l. Virus: 40% of individuals with congenital rubella infection develop diabetes
type 1 later, persistent cytomegalovirus infection appear relevant in some cases
of type 1 diabetes
m. There is a small number of adults (~10%) classifies as having type 2 who appear
to have immune mediated destruction of beta cells who actually fall into the
category of type 1A diabetes
i. It is called “latent autoimmune disease in adult” or LADA - otherwise,
type 1 diabetes is diagnosed in childhood for the most part
ii. Diagnosis peaks at 12 years of age and is rare before 9 months of age
2. Idiopathic Type 1B/Non-immune Type 1 Diabetes
a. No evidence of autoimmunity; the etiology is unknown
b. Accounts for <10% of those with type 1 diabetes
c. Strong genetic component to the development of type 1B diabetes
d. Most affected individuals are of African or Asian descent
e. Varying levels of insulin deficiency - episodic ketoacidosis
f. Affected individuals have varying degrees of insulin deficiency that can come
and go which leads to varying degrees of insulin deficiency that can come and
go which leads to episodic ketoacidosis
Etiology Type 2 DM
● Type 2 diabetes is a heterogeneous condition characterized by hyperglycemia,
insulin resistance and relative impairment in insulin secretion
● Range from predominant insulin resistance with relative insulin deficiency to
a predominant secretory defect with insulin resistance
● It is an environment-genetic interaction - 12-25% will develop either impaired glucose
tolerance or diabetes
● Variants of genes have been identified that increase the risk for Type 2 Diabetes:
○ Genetic defects of beta cell function
○ Genetic defects in insulin synthesis, secretion and action
○ Genes that encode proteins for pancreatic development
○ Amyloid deposition in beta cells
○ Cellular insulin resistance and impaired regulation of gluconeogenesis
● Risk factor for type 2 diabetes:
○ Age
○ Obesity
○ Hypertension
○ Physical inactivity
○ Family hx
○ Metabolic syndrome - high risk of developing type 2 diabetes with
cardiovascular complications
● Type 2 DM occurs mostly in adults
○ Canadian aboriginal children are particularly affected
about:blan 2/
k 17
, 10/9/24, 11:41 Diabete
AM s
Etiology GDM (Gestational) and Other
Gestational Diabetes Mellitus
● Any degree of glucose intolerance with onset or first recognition during pregnancy
● Pregestational diabetes - pregnancy in persons with pre-existing diabetes
● Combination of insulin resistance and impaired insulin secretion are most
definitely contributing factors
● Risk factors:
○ Older age
○ Family hx
○ Hx of glucose intolerance
○ Obesity
○ Membership in certain ethnic/racial group
○ Hx of poor obstetric outcomes and infant weighing greater than 9lbs
● Diagnosis is made based on the gestational diabetes screen which is a 50g glucose
load followed by a plasma glucose level 1h later
● Diagnosis of gestational diabetes is made based on different lab values
● Untreated gestational diabetes leads to increased maternal and perinatal morbidity
Other:
● Specific genetically defined forms of diabetes include: genetic defects of beta
cell function and genetic defects in insulin action
● MODY (Maturity Onset Diabetes of the Young) - specific grouping of
genetically defined form of diabetes
○ Individuals present at a young age have mild disease due to beta cell dysfunction
with some insulin production and inherit the disease via autosomal dominant
transmission
○ There is normal insulin sensitivity in individuals with MODY
○ These genetic abnormalities are not often referred to their specific description,
for example: MODY 2 excompasses over a dozen mutations in the glucokinase
on chromosome 7
Note:
● Beta cell dysfunction
● Some insulin production
● Normal insulin sensitivity
● Autosomal-dominant inheritance - genetic inheritance pattern where an abnormal
gene (inherited from one parent) is dominant over the normal gene (inherited
from another parent)
○ Individual characteristics associated with abnormal gene
about:blan 3/
k 17
