Diabetes

Question 1

Glucose?

Answer 1

• Glucose is leading energy source for humans
  
  • stored for rapid release
  • utilised in times of stress so that serum conc is maintained at level that provides constant supply of glucose to neurons-SNS
    
    • danger of high and low cycling
  • minute-to-minute control is function of endocrine pancreas gland
• HbA1c test provides 3-month average of glucose levles

Question 2

Talk to me about Insulin please

Answer 2

• Hormone
• Normally produced and released from pancreatic beta cells-endocrine part
  
  • Islets of Langerhans
    
    • alpha cells release glucagon in response to low glucose
    • beta cells release insulin in response to high glucose
      
      • work together to maintain serum glucose level within normal limits of 3.5-8mmol/L
• Stimulates adipose and muscle cells to uptake glucose
  
  • Binds to specific insulin receptor sites on cell membranes, stimulating transport of glucose into cells
    
    • by facilitated diffusion
• Also stimulates synthesis of glycogen (glucose stored for immediate releasure during times of stress/low glucose)
  
  • glucagon breaks down glycogen-glucose (liver)
• Insulin release reduced as blood glucose levels fall

Question 3

Hyperglycaemia

Answer 3

• Fasting blood sugar >11mmol/l
  
  • glycosuria (sugar in urine)-infection
  • cells cannot use glucose present-fatigue
  • hungry/thirsty
  • ketoacidosis-metabolism shifts to use of fat and ketone waste cannot be removed effectively-fruity breath-DANGER
  • muscle breakdown-need amino acids-protein in urine
  • slowed wound healing-all above
  • thickening of basement membrane in blood vessels, decreased blood flow
    
    • heart attacks/strokes
    • retinopathy (eyes)
    • neuropathies (feet and legs)
    • nephropathy (renal)

Question 4

Hypoglycaemia

Answer 4

• Blood sugar <3mmol/l
• starvation or too much insulin
• body reacts immediately because cells need glucose to survive-esp. neurons
• parasympathetic stimulation
  
  • increased GI activity-increase digestion and absorption
• SNS then responds by increasing Blood glucose levels
  
  • glucagon, breakdown of fat/glycogen
• Signs: nervousness, anxiety, sweating, pale, cool, headache, shakiness
  
  • extreme-loss of consciousness and coma

Question 5

Talk to me about Diabetes Mellitus (Honey Urine) Type I and treatment options?

Answer 5

• Don’t produce Insulin
• Usually only onset-childhood
  
  • don’t know how or why, just suddenly happens? genetic link? viral destruction?
• <10%
  
  • (although now thoughts that there may be several more sub-types of diabetes)
• Currently treatment aimed at tightly regulating blood sugar levels through use of Insulin
  
  • transplantation-successful but experimental

Question 6

What are the side effects of insulin replacements?

Answer 6

• Fat hypertrophy at injection site
• transient oedema
• local reaction at injection site
• Other options? external/implantable insulin pump, inhaled insulin, insulin patch

Question 7

When are Insulin replacements used?

Answer 7

• Diebetes mellitus, type I
  
  • sometimes in type II if not controlled by diet/pills, ketoacidosis or frequent hypoglaecimias
• OK in pregnancy and breastfeeding
• NOT if MAOIs-decrease glucose levels
• Allergies to animal insulin-although now most are human analogues-made in laboratories using recombinant DNA technology and E. Coli

Contraindications (and side effects) include;

• hypoglycaemia
• ketoacidosis

Question 8

Outline Humalog

Answer 8

Rapid-acting

• starts working within 15mins (peak = 1 hour)
• used in adults + children over 3 years old

Question 9

Outline Humulin 1

Answer 9

Intermediate-acting

• Peak activity between 1-8 hours
• Human isophane insulin

Question 10

Glargine

Answer 10

Long-acting

• baseline over 24 hours
• Human insulin analogue

Question 11

Novomix 30

Answer 11

mixed

• biphasic insulin
• Short acting - contains 30% soluble insulin aspart
• intermediate acting - contains 70% insulin aspart crystalised with protamine

Question 12

Talk to me about Diabetes Mellitus (Honey Urine) Type II and treatment options?

Answer 12

• Mature adults (increasing in teenagers/young adult)
  
  • slow and progressive onset
    
    • Can be related to life-style factors
• Cells don’t produce enough Insulin OR Insulin resistance OR person may not have enough receptor sites to support body size-obesity
• >90% of cases
• Initial treatment
  
  • diet-control amount and timing, and weight loss decrease Rs needed
  • exercise-increases movement of glucose into cells by activation of SNS and increase in K+
    
    • When no longer work, oral angents and possibly eventually insuline

Question 13

What happens with Insulin Resistance?

Answer 13

• receptors do not recognise insulin
  
  • glucose stays in the blood
  • pancreas keeps releasing Insulin as seems that not effective
  • blood becomes heavy with Insulin-increased BP
  • can’t use enegry-tired, sluggish, hungry

Question 14

What are the contraindications of Oral Agents?

Answer 14

• Keotacidosis for all
• Bladder? for Pioglitazone
• Allergies
• Pregnancy

Question 15

Gliclazide

Answer 15

• Sulphonylurea-first oral agents-often baseline, others added/combined
• Augmenting insulin secretions
  
  • acts on beta cells (so activity needs to be present)
  • closes K+ channels causing membrane depolarisation
  • Ca2+ enters the cell, signalling exocytosis of insulin

Question 16

What are the side effects of Gliclazide?

Answer 16

• Hypoglycaemia
• Blood Disorders

Question 17

Exenatide

Answer 17

Incretin mimetic hormone that agonises GLP-1 Receptor on beta cells in pancreas to;

• Increases Insulin Secretion
• Supresses Glucagon secretion
• Slows gastric emptying

Question 18

What are the side effects of Exenatide?

Answer 18

• Abdominal Pain
• Diarrhoea
• Agitation
• Decreased Appetite

Question 19

Sitagliptin

Answer 19

DPP4 inhibitor-slows inactivation of incretin hormones-including GLP-1

• increases insulin secretion
• Also lowers glucagon secretion

Question 20

What are the side effects of Sitagliptin?

Answer 20

• GI disturbances
• Pain
• Peripheral odeoma

Question 21

Metformin

Answer 21

Biguanides-acts in liver

• decreases gluconeogenesis
• increases peripheral utilisation of glucose
• increases uptake of glucose by skeletal muscle

Question 22

What are the side effects of Metformin?

Answer 22

• GI disturbances
• Taste Disturbances
• Anorexia Nervosa

Question 23

Pioglitazone

Answer 23

TZD

• acts on Insulin Receptor Sites
• reduces peripheral insulin resistance
• leading to reduced blood-glucose concentration

Question 24

What are the side effects of Pioglitazone?

Answer 24

• Anaemia
• Dizziness
• Headaches

Question 25

Dapagliflozin

Answer 25

* Irreversibly inhibits Sodium-Glucose Transporter (SGLT-2) * reduce glucose reabsorption in the kidney * responsible for at least 90% of Glucose reabsorption in the kidney * blocking causes increased urinary glucose excretion *

Question 26

What are the side effects of Dapagliflozin?

Answer 26

* Constipation * Thirst * Back Pain * Thirst

Question 27

Obesity-Orlistat

Answer 27

* Lipase inhibitor * reduces absorption of dietary fat

Question 28

What are the side effects of Orlistat?

Answer 28

* Fecal incontinence * Anxiety * Headaches * abdominal pain

Question 29

What are the contraindications of Orlistat?

Answer 29

* Malabsorption of fat-soluble vitamins * cholestasis (reduction of bile flow)