This document discusses diabetes mellitus, including its types and pathophysiology. It defines diabetes as a chronic metabolic disorder where the body cannot properly metabolize carbohydrates, fats and proteins due to lack of or ineffective insulin. The three main types are type 1, type 2, and gestational diabetes. Complications for both mother and fetus are explained.
2. DiabetesMellitus
Chronic metabolic disorder
Body cannot metabolise fats, carbohydrates,
and proteins because of a lack of, or
ineffective use of the hormone insulin
classified into three primary types that are
different disease entities but share the
symptoms and complications of
hyperglycemia (high blood glucose)
3. DiabetesMellitus
Type I Diabetes Mellitus:
Previously “Insulin Dependent Diabetes Mellitus” (IDDM)
Or Juvenile-Onset Diabetes
Type II Diabetes Mellitus:
Previously “Non-Insulin Dependent Diabetes Mellitus”
(NIDDM)
Or Adult-Onset Diabetes
Gestational Diabetes Mellitus:
Or GDM
4. NormalCarbohydrateMetabolism
andInsulinAction
Following the consumption of food,
carbohydrates are broken down into glucose
molecules in the gut
Glucose is absorbed into the bloodstream
elevating blood glucose levels
This rise in glycaemia stimulates the
secretion of insulin from the beta cells of the
pancreas
Insulin is needed by most cells to allow
glucose entry
5. NormalCarbohydrateMetabolism
andInsulinAction
Insulin binds to specific cellular receptors and
facilitates entry of glucose into the cell, which
uses the glucose for energy
The increased insulin secretion from the
pancreas and the subsequent cellular
utilization of glucose results in lowered of
blood glucose levels
Lower glucose levels then result in decreased
insulin secretion
6. NormalCarbohydrateMetabolism
andInsulinAction
Following meals, the amount of glucose
available from carbohydrate breakdown
often exceeds the cellular need for glucose
Excess glucose is stored in the liver in the
form of glycogen, which serves as a ready
reservoir for future use
When energy is required, glycogen stores in
the liver are converted into glucose via
glycogenolysis, elevating blood glucose levels
and providing the needed cellular energy
source
7. NormalCarbohydrateMetabolism
andInsulinAction
The liver also produces glucose from fat (fatty
acids) and proteins (amino acids) through the
process of gluconeogenesis
Glycogenolysis and gluconeogenesis both
serve to increase blood glucose levels
Thus, glycaemia is controlled by a complex
interaction between the gastrointestinal
tract, the pancreas, and the liver
8. TheRoleof Insulinin
hyperglycaemiaandhypoglycaemia
If insulin production and secretion are altered by
disease, blood glucose dynamics will also change
If insulin production is decreased, glucose entry
into cells will be inhibited, resulting in
hyperglycaemia
The same effect will be seen if insulin is secreted
from the pancreas but is not used properly by
target cells
If insulin secretion is increased, blood glucose
levels may become very low (hypoglycaemia) as
large amounts of glucose enter tissue cells and
little remains in the bloodstream.
9. TypeI DiabetesMellitus
Beta cells of pancreas are destroyed or
suppressed
Subdivided into idiopathic and immune-
mediated types
10. TypeI DiabetesMellitus
Onset is usually abrupt, before 30 years of
age but may be diagnosed at any age
Type I Diabetics are usually of normal weight,
or may be thin in stature
Since the pancreas produces absolutely no
insulin, the patient must rely on exogenous
insulin, administered for survival
Patients are highly susceptible to diabetic
ketoacidosis
11. TypeI DiabetesMellitus
PathophysiologyofIdiopathicDiabetesMellitus
With idiopathic type, patients have a
permanent insulin deficiency with no
evidence of autoimmunity
Often lack antibodies found in immune-
mediated type 1 diabetes
May be able to go without insulin therapy for
some periods of time
12. TypeI DiabetesMellitus
PathophysiologyofImmune-MediatedDiabetes
Occurs when there is autoimmune
destruction in which the body secretes
substances that attack and destroy the beta
cells in the islets of Langerhans within the
pancreas
This attack causes an inflammatory response
in the pancreas called insulitis, ceasing insulin
production
One or more key antibodies are found in 85-
90% of people with this form of type 1
diabetes
13. DiabeticKetoacidosis(DKA)
Inadequate insulin hinders glucose uptake by
fat and muscle cells
Glucose accumulates in blood
Liver responds to demands of energy starved
cells by converting glycogen to glucose,
further increasing blood glucose levels
When glucose levels exceed renal threshold,
excess excreted in urine
Insulin-deprived cells respond by rapid
metabolism of proteins
14. DiabeticKetoacidosis(DKA)
Results in loss of intracellular potassium and
phosphorus and excessive liberation of amino
acids
Liver converts these acids into urea and
glucose
Blood glucose levels grossly elevated
Results in increased serum osmolarity and
glucosuria, leading to massive fluid loss from
osmotic diuresis causing fluid and electrolyte
imbalances
15. DiabeticKetoacidosis(DKA)
Water loss excedes glucose and electrolyte
loss, contributing to hyperosmolarity
This perpetuates dehydration, decreasing the
glomerular filtration rate and reducing
amount of glucose excreted in urine
DEADLY CYCLE:
Diminished glucose excretion raises blood
glucose levels hyperosmolarity and
dehydration SHOCK COMA DEATH
16. DiabeticKetoacidosis(DKA)
SIMULTANEOUSLY – Absolute insulin
deficiency causes cells to convert fats into
glycerol and fatty acids for energy
Fatty acids can’t be metabolised as quickly as
released, so accumulate in liver
Converted to ketones (ketoacids)
Ketones accumulate in blood and urine
(acidosis)
Acidosis leads to more tissue breakdown
More ketosis More acidosis Eventually
SHOCK COMA DEATH
17. TypeII DiabetesMellitus
Caused by:
Resistance to insulin action in target tissues
Abnormal insulin secretion
Inappropriate hepatic gluconeogenesis (over
production of glucose)
Consequence of obesity and sedentary lifestyle
18. TypeII DiabetesMellitus
Pathophysiology
Problems arise when insufficient insulin
produced or body (fat, muscle or liver) cells
resist insulin
When body cells develop a resistance to
insulin, there is a difficulty with glucose
entering cells
As a result, cells don’t get enough energy
Lack of energy causes glucose to build up in
the blood vessels
Can result in damage to body organs
especially if poorly managed
19. GestationalDiabetesMellitus
Gestational diabetes mellitus (GDM) is
defined as glucose intolerance of variable
degree with onset or first recognition during
pregnancy
The placental hormones – oestrogen,
placental lactogen , glucagon and cortisol
interfere with insulin receptors making the
woman temporarily diabetic
Usually develops in the second or third
trimester
20. GestationalDiabetesMellitus
Risk factors for gestational diabetes include:
Advanced maternal age (>30 years)
Ethnicity (Maori, Pacific Islander, Indian, Chinese)
Obesity (Prepregnancy BMI >30
– dependent on ethnicity)
Obstetrical history of diabetes , unexplained still birth
or neonatal death or macrosomia
Strong family history of diabetes
Glucosuria on two separate occassions in current
pregnancy
Multiple pregnancy
21. DiabetesinPregnancy
Pregnancy characterised by several factors that
produce a diabetogenic state
Insulin and carbohydrate metabolism is altered
in order to make glucose more readily available
to the fetus
Women with DM do not have the capacity to
increase insulin secretion in response to the
altered carbohydrate metabolism in pregnancy
Glucose therefore accumulates in the maternal
and fetal system, leading to significant morbidity
and mortality
22. SignsandSymptoms
Polyuria and polydipsia: Polyuria is due to
osmotic diuresis secondary to hyperglycemia.
Thirst is due to the hyperosmolar state and
dehydration
Polyphagia with weight loss or muscle
wasting:The weight loss with a normal or
increased appetite is due to depletion of
water and a catabolic state with reduced
glycogen, proteins, and triglycerides
23. SignsandSymptoms
Fatigue and weakness:This may be due to
muscle wasting from the catabolic state of
insulin deficiency, hypovolemia, and
hypokalemia
Nocturnal enuresis (bed-wetting): Severe
enuresis secondary to polyuria can be an
indication of onset of diabetes in young
children
24. SignsandSymptoms
Blurred vision:This also is due to the effect of
the hyperosmolar state on the lens and
vitreous humor. Glucose and its metabolites
cause dilation of the lens, altering its normal
focal length
Muscle cramps:This is due to electrolyte
imbalance
25. SignsandSymptoms
Gastrointestinal symptoms: Nausea,
abdominal discomfort or pain, and change in
bowel movements may accompany acute
DKA. Acute fatty liver may lead to distention
of the hepatic capsule, causing right upper
quadrant pain. Persistent abdominal pain
may indicate another serious abdominal
cause of DKA, eg, pancreatitis. Chronic
gastrointestinal symptoms in the later stage
of diabetes are due to visceral autonomic
neuropathy
26. SignsandSymptoms
Peripheral neuropathy:This presents as
numbness and tingling in both hands and
feet, in a glove and stocking pattern. It is
bilateral, symmetric, and ascending
neuropathy, which results from many factors,
including the accumulation of sorbitol in
peripheral sensory nerves due to sustained
hyperglycemia
27. SignsandSymptoms
Symptoms at the time of the first clinical
presentation can usually be traced back several
days to several weeks; however, beta cell
destruction may have started months, or even
years, before the onset of clinical symptoms
28. FetalComplications
Miscarriage
In women with pre-existing diabetes, there is a 9-
14% risk of miscarriage
Supoptimal glycaemic control and advanced
diabetes also posses a significant risk
29. FetalComplications
Birth Defects
With DM the risk of structural abnormality is increased
to 5-10% (normally 1-2%)with poor glycaemic control
prior to conception
Two-thirds of anomalies affect the cardiovascular and
nervous systems
Neural tube defects occur 13-20 times more frequently
in diabetic women
Genitourinary, gastrointestinal, and skeletal anomalies
are also more common
Because birth defects occur during the critical 3-6 weeks
after conception, nutritional and metabolic intervention
must be initiated well before pregnancy begins
30. FetalComplications
Fetal Growth Restriction
IUGR occurs significantly in pregnancy where
women have pre-existingType 1 DM
The most important predictor of fetal growth
restriction is underlying maternal vascular disease
Specifically, pregnant patients with diabetes-
associated retinal or renal vasculopathies and/or
chronic hypertension are most at risk for growth
restriction
31. FetalComplications
Fetal Growth Acceleration
Caused by excessive body fat stores, stimulated by
excessive glucose delivery during diabetic
pregnancy
Approximately 30% of fetuses of women with
diabetes mellitus in pregnancy are large for
gestational age (LGA). In pre-existing diabetes
mellitus this incidence appears slightly higher, 38%
Maternal obesity, common in type 2 diabetes,
appears to significantly accelerate the risk of infants
being LGA
32. FetalComplications
Fetal Obesity
The macrosomic fetus in diabetic pregnancy
develops a unique pattern of overgrowth, involving
central deposition of subcutaneous fat in the
abdominal and interscapular areas. Skeletal growth
is largely unaffected
Macrosomia is typically defined as a birthweight
above the 90th percentile for gestational age or
greater than 4000 grams
Birth injury, including shoulder dystocia and brachial
plexus trauma, are more common among infants of
diabetic mothers, and macrosomic fetuses are at the
highest risk
33. FetalComplications
Metabolic Syndrome
Glucose intolerance and higher serum insulin levels
are more frequent in children of diabetic mothers as
compared to normal controls
The childhood metabolic syndrome includes
childhood obesity, hypertension, dyslipidemia, and
glucose intolerance
Fetuses of diabetic women that are born large for
gestational age appear to be at the greatest risk
34. FetalComplications
BirthTrauma
Injuries of birth, including shoulder dystocia and
brachial plexus trauma, are more common among
infants of diabetic mothers
Common birth injuries associated with diabetes are
brachial plexus, facial nerve injury, and
cephalohematoma
35. FetalComplications
Polycythaemia
Hyperglycemia is a powerful stimulus to fetal
erythropoietin production mediated by decreased
fetal oxygen tension
Hypoglycaemia
Aproximately 15-25% of neonates delivered from
women with diabetes during gestation develop
hypoglycemia during the immediate newborn
period
Unrecognized postnatal hypoglycemia may lead to
neonatal seizures, coma, and brain damage
36. FetalComplications
Hyperbilirubinaemia
Causes of hyperbilirubinemia in infants of diabetic
mothers are multiple, but prematurity and
polycythemia are the primary contributing factors
Increased destruction of red blood cells contributes
to the risk of jaundice and kernicterus
37. FetalComplications
Respiratory Problems
The majority of the literature indicates a significant
biochemical and physiological delay in infants of
diabetic mothers
Fetal lung maturity is thought to occur later in
pregnancies with poor glycaemic control regardless
of class of diabetes
38. MaternalComplications
Diabetic Retinopathy
Leading cause of blindness in women aged 24-64 years
Some form of retinopathy is present in virtually 100% of
women who have had type 1 diabetes for 25 years or
more
Studies show that while half the women with pre-
existing retinopathy experienced deterioration during
pregnancy, all the patients had partial regression
following delivery and returned to their prepregnant
state by 6 months postpartum
Rapid induction of glycaemic control in early pregnancy
stimulates retinal vascular proliferation
39. MaternalComplications
Renal Function
In general, patients with underlying nephropathy can
expect varying degrees of deterioration of renal
function during a pregnancy
As renal blood flow and glomerular filtration rate
increase 30-50% during pregnancy, the degree of
proteinuria will also increase
Perinatal complications are greatly increased in
patients with diabetic nephropathy. Preterm birth,
intrauterine growth restriction, and preeclampsia are
all significantly more common in women with diabetic
nephropathy during pregnancy
40. MaternalComplications
Chronic Hypertension
Complicates approximately 1 in 10 diabetic
pregnancies overall
Patients with underlying renal or retinal vascular
disease are at a substantially higher risk
Patients with chronic hypertension and diabetes are
at increased risk of intrauterine growth restriction,
superimposed preeclampsia, abruptio placentae,
and maternal stroke
41. MaternalComplications
Pre-Eclampsia
Preeclampsia is more frequent among women with
diabetes, occurring in approximately 12% as compared
to 8% of the nondiabetic population
The risk of preeclampsia is also related to maternal age
and the duration of preexisting diabetes
In patients who have chronic hypertension coexisting
with diabetes, preeclampsia may be difficult to
distinguish from near-term blood pressure elevations
The rate of preeclampsia has been found to be related
to the level of glycemic control and pregravid body
mass index
42. TestsandInvestigations
HbA1c
HbA1c is a test that measures the amount of
glycosylated hemoglobin in blood
Glycosylated hemoglobin is a molecule in red
blood cells that attaches to glucose (blood sugar)
Elevated levels of glycosylated hemoglobin if
there more glucose in the blood
The test gives a good estimate of how well
diabetes is being managed over the last 2 or 3
months (life of erythrocyte)
No preparation or fasting required prior
43. TestsandInvestigations
HbA1c
Results
An elevated HbA1c increases the risk of
complications such as retinopathy, nephropathy,
neuropathy, heart disease, and stroke
Especially true if HbA1c remains high for a long
period of time
HbA1c normally 3-6%
Abnormal results mean that blood glucose levels
have not been well-regulated over a period of weeks
to months
If HbA1c is above 7%, it means diabetes is poorly
controlled
44. TestsandInvestigations
Polycose
Woman without known diabetes should be
offered routine screening for GDM
Test is a non fasting 1 hour 50g glucose challenge
test, preferably in morning
One hour later, blood is taken
Performed at 24-28 weeks of pregnancy
Women need written and full information about
this so they can make an informed choice
45. TestsandInvestigations
Polycose
Results
If result is >7.8 mmol/L
GTT
If result is 7.2 – 7.7 mmol/L
Rescreen 2 weeks later if known risk
factors for GDM
If result is <7.8 mmol/L but known risk factors are
present
Offer rescreening or GTT to assess whether
glucose tolerance deteriorating
46. TestsandInvestigations
GlucoseToleranceTest
Test is a fasting 75g glucose tolerance test
Blood is taken:
- Prior to test
- 1 hour after glucose load
- 2 hours after glucose load
Usual diet in days prior to the test
Fast for 12 hours prior to the test
Repeat if clinically indicated, even though first
GTT has been normal
48. Section88 MaternityNotice
ReferralGuidelines
LEVEL 3 (Code 1019)
- Pre-existing DM Insulin Dependent or Non Insulin
Dependent
LEVEL 2 (Code 1020)
- GDM well controlled on diet
LEVEL 3 (Code 1021)
- GDM requiring Insulin
Consideration of ‘Shared Care’ or intrapartum
midwifery care may be an option for women
with GDM
50. Management
Pre-PregnancyCareforType1or2DM
Assessment is made of current diabetic control,
aiming for pre-meal glucose of <6 mmol/L and
HbA1c of ≤7%
Insulin dosage reviewed
Women withType 2 DM on oral hypoglycaemics
will need to transfer to insulin to prevent
possibility of teratogenesis
Higher-dose folic acid supplementation
Smoking cessation support is arranged
Assessment and management is provided for
diabetes complications
51. Management
Pre-ExistingDiabetesMellitus
Booking visit – care recommendations and options
Ideally should be seen in a combined clinic by a team
that includes a physician, obstetrician, specialist
diabetes nurse, specialist midwife and dietician
Seen as often as required in order to maintain good
diabetic control and undertake relevant screening
Blood glucose levels should be monitored frequently
(4-8x per day using reflective meter) and insulin levels
adjusted accordingly
Additional estimations of blood glucose control, such as
monthly HbA1c measurements recommended
Diet high in fibre beneficial as carbohydrates released
slowly and therefore more constant BSL can be
achieved
52. Management
Pre-ExistingDiabetesMellitus
Advise women on early recognition of the signs and
symptoms of urinary and vaginal infections
Anomaly ultrasound should be offered at 20 weeks
gestation, and consider fetal echocardiography at
20-22 weeks to detect cardiac abnormalities
Serum screening for Down Syndrome is altered with
maternal diabetes and care should be taken when
interpreting results
A baseline measurement of the fetal AC should be taken
at 20 weeks gestation, followed by serial measurements
every 2-4 weeks commencing at 24 weeks to detect
IUGR, macrosomia and polyhydramnios
See in daily assessment unit if problems or on wards if
inpatient
53. Management
GestationalDiabetesMellitus
After screening and confirmation, referral according to
Section 88 Guidelines
Educate women regarding complications of
uncontrolled blood glucose levels on her health and her
baby’s
Partake in 3-way discussion as MultidisciplinaryTeam
member
Good communication with women regarding scope
and with other professionals regarding care
Refer if Blood glucose levels high/unstable
Be aware of local protocols
Continue to support, educate, offer continuity of care
eg. for postnatal care, etc
54. Medications
Insulin
NovoRapid
Insulin aspart, whereby its molecules enable the
uptake of glucose into cells by binding onto
receptor sites and concurrently preventing the
release of glucose from the liver
Dosage is based on the needs of the patient when
reviewed by the physician and facilitates a quick
onset of action when comparing it to human
insulin, and a shorter duration of action after
subcutaneous injection
Unlike glucose however, insulin does not cross the
placental barrier
55. Medications
Insulin
Protaphane
Similar to NovoRapid
Is an isophane insulin suspension and its actions
are equal to that of human insulin
One significant difference is that its time of onset
is 1.5 hours, longer than NovoRapid and long
acting, lasting for up to 24 hours
Again, the dose is patient-dependent, and
determined by the physician in accordance with
the needs of the patient
56. Medications
Metformin
Metformin is a biguanide by-product, which produces an
antihyperglycaemic effect where there is insulin secretion
from the pancreas, although the action of the drug is not fully
understood
It is suggested that it may mimic or improve the effects of
insulin on peripheral receptor sites, and that this increased
sensitivity appears to be a result of an increase in the amount
of insulin receptor sites on the cell surface
Other proposed mechanisms of action include glucogenesis
inhibition within the liver or a delay in the absorption of
glucose from the gastrointestinal tract
In pregnancy metformin does cross the placenta, however
there is no research to indicate that metformin is teratogenic