diabetes mellitus

DIABETES MELLITUS

Diabetes Mellitus

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)

Diabetes Mellitus

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

Normal Carbohydrate Metabolism and Insulin Action 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

Normal Carbohydrate Metabolism and Insulin Action 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

Normal Carbohydrate Metabolism and Insulin Action 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

Normal Carbohydrate Metabolism and Insulin Action 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

The Role of Insulin in hyperglycaemia and hypoglycaemia 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.

Type I Diabetes Mellitus

Beta cells of pancreas are destroyed or suppressed

Subdivided into idiopathic and immune-mediated types

Type I Diabetes Mellitus

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

Type I Diabetes MellitusPathophysiology of Idiopathic Diabetes Mellitus 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

Type I Diabetes MellitusPathophysiology of Immune-Mediated Diabetes 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

Diabetic Ketoacidosis (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


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


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


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

Type II Diabetes Mellitus

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

Type II Diabetes MellitusPathophysiology

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

Gestational Diabetes Mellitus

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

Gestational Diabetes Mellitus

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

Diabetes in Pregnancy

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

Signs and Symptoms

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

Signs and Symptoms

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

Signs and Symptoms

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

Signs and Symptoms

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

Signs and Symptoms

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

Signs and Symptoms

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

Fetal Complications

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

Fetal Complications

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

Fetal Complications

Fetal Growth Restriction IUGR occurs significantly in pregnancy

where women have pre-existing Type 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

Fetal Complications

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

Fetal Complications

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

Fetal Complications

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

Fetal Complications

Birth Trauma 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

Fetal Complications

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

Fetal Complications

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

Fetal Complications

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

Maternal Complications

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


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


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


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

Tests and InvestigationsHbA1c

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

Tests and InvestigationsHbA1c

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

Tests and InvestigationsPolycose

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

Tests and InvestigationsPolycose

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

Tests and InvestigationsGlucose Tolerance Test

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

Tests and InvestigationsGlucose Tolerance Test

Results Gestational Diabetes Mellitus confirmed

if: Fasting glucose: 5.5 mmol/L or greater 2 hour glucose: 9.0 mmol/L or greater

Section 88 Maternity NoticeReferral Guidelines

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

Section 88 Maternity NoticeReferral Guidelines

LEVEL 3 (Code 8044)- Infant of a Diabetic Mother with any abnormal findings e.g.

Hypoglycaemia Poor feeding Macrosomia

ManagementPre-Pregnancy Care for Type 1 or 2 DM

Assessment is made of current diabetic control, aiming for pre-meal glucose of <6 mmol/L and HbA1c of ≤7%

Insulin dosage reviewed Women with Type 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

ManagementPre-Existing Diabetes Mellitus

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

ManagementPre-Existing Diabetes Mellitus

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

ManagementGestational Diabetes Mellitus

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 Multidisciplinary Team 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

MedicationsInsulin

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

MedicationsInsulin

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

MedicationsMetformin

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

diabetes mellitus

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