Diabetes

• Diabetes is both a symptom and a disease
• The disease diabetes occurs when there are problems with the body’s regulation of serum glucose levels or antidiuretic hormone (ADH) levels both of which are characterized by polyuria
• About 10% of Canadians have diabetes and it is the most common endocrine dysfunction
• Diabetes causes at least 2X increase in mortality
• 2 types of diabetes

  1. Diabetes mellitus
  2. Diabetes insipidus
• Diabetes Mellitus

  • “Lots of sweet urine” or “sugar diabetes”
  • The urine is sweet because there is lots of sugar in it
  • There is lots of urine because the dissolved sugar in the urine draws water into the urine by osmosis. The sugary urine is excreted in large quantities
• Diabetes insipidus

  • “Lots of tasteless urine”
  • A disease of where this a lack of, or lack of responsiveness to antidiuretic hormone (ADH)
  • ADH works to concentrate the urine
• Diabetes Insipidus

  • The common cause for this disease is a decrease or blockage of the secretion of antidiuretic hormone (ADH)
  • Happens in the CNS
  • May be due to trauma to the stalk connecting the pituitary to the hypothalamus. This stalk is called the infundibulum
  • Pituitary tumors or the surgery on tumors as well as infection of the pituitary and hypothalamus can also lead to damage
  • Without ADH water is not as well reabsorbed from the filtrate back into the blood
  • Poor water reabsorption results in increased urine flow
  • The treatment is ADH (can be supplied in a nose spray)
• A less common cause of DI is nephrogenic DI

  • Results from the kidney becoming insensitive to the ADH
  • Damage is often secondary to drug use (e.g. lithium, demeclocycline, amphotericin B)
  • The treatment is to consume adequate amounts of fluid to avoid dehydration and and alterations in electrolyte levels
  • Rare: 1 case in 25,000 people
• ADH pathway

  • Neurosecretory cells are stored in the supraoptic nucleus of the hypothalamus
  • High blood osmotic pressure (such as when you are dehydrated) stimulates neurosecretory cells in the hypothalamus to release ADH in the posterior pituitary
  • ADH leaves the pituitary and travels to the kidney where it causes the kidney to reabsorb water from the filtrate. It also increased blood pressure and inhibits sweating
• Insulin

  • A water soluble polypeptide released by the beta cells of pancreas
  • Attaches to a cell surface receptor that has intrinsic tyrosine kinase activity
• Insulin causes:

  • Increase facilitated diffusion of glucose into cells
  • Conversion of glucose into glycogen
  • Synthesis of fatty acids
  • Synthesis of proteins from amino acids
  • Slows glycogen breakdown into glucose (glycogenolysis)
  • All these processes lower the blood glucose levels and thus will ultimately inhibit insulin release
  • Negative feedback to maintain glucose homeostasis
• Exocrine acinus: about 99% of the pancreas volumes consist of exocrine acini. They secrete 1200-1500 ml of pancreatic juice per day. The fluid contains digestive enzymes and bicarbonate to buffer the gastric juice
• Beta cells: secrete insulin when blood glucose in high and when there is a parasympathetic stimulation
• Alpha cells: secrete glucagon when blood glucose is low but also when there is sympathetic stimulation. Glucagon leads to glucose production in the liver
• Diabetes Mellitus

  • In both types, blood sugar stays high (hyperglycemia) after meals, sugar is spilled into the urine (glycosuria/glucosuria) and the much urine is produced (polyuria
• 2 types of diabetes mellitus

  1. Insulin dependent diabetes mellitus (IDDM or Type 1)
  2. Non-insulin dependent diabetes mellitus (NIDDM or Type 2)
• Type 1 Diabetes

  • A result of inadequate production of insulin
  • The beta cells which are responsible for insulin production do not work
  • Always treated with insulin which decreases blood sugar
  • This disease usually occurs in young adults, so it is sometimes called “juvenile onset diabetes”
  • The beta cells seem to be ruined by an autoimmune response, but in 5% the insulinopenia is due to other factors
  • Often the insulin is delivered with a pump but in the past it was an injection
• The effect of a lack of insulin

  • The cells which rely on insulin for sugar begin to starve
  • As the cells starve, they begin to burn fat in large quantities
• The effect of a lack of insulin

  • Burning of fat leads to the production of poorly metabolized fragments of fat which are called “ketone bodies”
  • The ketone bodies include odorous molecules like acetone so the breath smells fruity
  • The ketone bodies are also acidic so the blood pH falls, this is called ketoacidosis
• The effect of a lack of insulin

  • All the fat in circulation begins to deposit on blood vessel walls causing vascular damage
  • As a consequence of the vascular damage, the retinas can be damaged, and gangrene can occur in the hands and feet
• The effect of a lack of insulin

  • The person loses weight and is constantly hungry
  • The person begins to starve to death even though there is plenty of sugar in the blood
  • This insulin dependence occurs in only very severe Type 2 diabetes, since most NIDDM have high adiposity
• Diabetic Foot Ulcers

  • The large amounts of lipids in the bloodstream and other problems caused by hyperglycemia lead to damage to the arterial walls and poor circulation
  • Areas which are predisposed to poor circulation and have friction will tend to ulcerate and may become infected and need to be amputated
  • 70% of all non-traumatic leg and foot amputations are due to diabetes
• Non-insulin dependent diabetes mellitus/ Type 2 Diabetes

  • Associated with adulthood and is sometimes called adult-onset diabetes
  • A result of inadequate response to insulin
  • The cells which should be responding to insulin are resistant to the effects of insulin
  •  There is usually enough insulin response to keep ketoacidosis from occurring but not enough to stop hyperglycemia
  • After a long period of Type 2 diabetes, the beta cells begin to wear out and insulin make become necessary
• Non-insulin dependent diabetes mellitus/ Type 2 Diabetes

  • Increases in body weight and high body weight
  • About 90% of the type 2 case are in people with obesity
  • 36.3% of adults are living with overweight
  • 26.8% are living with obesity
  • Certain cultural groups are particularly at risk of this disease suggesting that genetics plays a major role
  • Treatment is usually diet, exercise and oral hypoglycemics (like metformin)
  • Showing up in juvenile populations due to increase in childhood obesity
  • 23.7% of youth are living with overweight or obesity
• Pregnancy and Blood Sugar

  The same regulatory systems are in place to deal with blood sugar whether someone is pregnant or not
• The fetus only receives blood glucose from the maternal circulation, but it deals with blood sugar in the same way as the adult
• The fetus constantly takes in sugar across the placenta to continue to grow and that sugar comes from the maternal bloodstream
• During pregnancy hypoglycemia (low blood sugar) may occur during sleep.

  This occurs because the fetus continues to draw glucose across the placenta from the maternal bloodstream, even during periods of fasting.
• • Fasting glucose levels in pregnancy are about 10-20% lower than in non-pregnant women.
• • Some hormones produced during pregnancy cause the maternal cells, which normally respond to insulin, to resist the effects of insulin and not take up glucose
  • These effects are most pronounced later in pregnancy when the reproductive hormone levels are highest
• • Insulin levels are 30% higher in the third trimester compared to the non-pregnant state.
  • The reduced maternal response to insulin allows the baby to get more glucose to grow
  • Insulin increases by the pregnant person may not be enough to keep increases of blood sugar after meals in the normal range thus we call pregnancy diabetogenic (i.e., it can cause diabetes)
• • When diabetes occurs as a new disease in pregnancy it is called Gestational Diabetes mellitus (GDM)
  • Abnormal glucose regulation occurs in 3-10% of pregnancies
  • 80% or more of this glucose intolerance occurs with gestational diabetes mellitus (GDM)
• • The risk magnitude of these morbidities in individual cases is proportional to

  the degree of maternal hyperglycemia

  • The diabetes can be screened for using an oral glucose challenge test.
• What happens with high maternal glucose

  • The increased glucose in maternal circulation moves through the placenta to the fetus which causes the fetus to secrete large amounts of insulin
  • This can cause an increase in the among to fat produced (lipogenesis) but the baby
  • Maternal insulin cannot get across to the fetus because the placenta destroys the peptide
• • High insulin and glucose in the baby also stimulates the release of insulin-like growth factors (IGFs)
  • The baby becomes much larger (macroscomic) but not more developed
  • Increased maternal and neonatal death rates
  • C-section delivery for cephalopelvic disproportion and for non-progression of labor is twice as frequent if the infant has macrosomia (19% v 8%)
  • Brachial plexus paralysis and clavicular fractures are more frequent in infants weighing more than 4000g than in smaller infants (2.5% v 0.01% and 5.5% v 0.06% respectively)
• The fetus develops chronic hyperinsulinemia (high insulin levels) to deal with high sugar load
• • The glucose challenge is simply a drink with a lot of glucose, usually 75g
  • A standard tests for pregnant people in some areas of canada
• Altered response to glucose is a part of normal pregnancy and facilitates fetal growth
• The normal maternal response to glucose in the 3rd trimester looks a lot like type 2 diabetes