Diabetes Flashcards
What is Diabetes?
- group of metabolic disorders
- characterised by hyperglycaemia
- results from defect in insulin secretion, insulin action or both
What are the symptoms of Diabetes?
- polyuria
- polydypsia
- weightloss
- fatigue
- blurred vision
*chronic = susceptible to certain infections
What are some acute life threatening consequences of uncontrolled diabetes?
- Ketoacidosis
- non ketoacidosis hyperosmolar syndrome
What are the types of diabetes? Explain.
Type 1:
- auto immune mediated
- juvenile
- absolute deficiency of insulin
Type 2:
- life style dependent
- combination of resistance to insulin action and inadequate compensatory insulin secretory response
Do individuals with normal glycemic control need insulin?
- No
- Individuals with adequate insulin glycemic control with weight reduction, exercise, oral glucose lowering agents do not require insulin
- Individuals with some residual exogenous insulin for adequate glycemic control can survive without it
Do individuals with extensive b-cell destruction with no residual insulin secretion need insulin?
Yes
What are the glucose levels according to the ADA on an empty stomach and 2 hours after a meal?
- Empty stomach: > 7 mmol/L (126mg/dl)
- 2 hours after a meal: > 11.1 mmol/L (200mg/dl)
What are some long term complications from diabetes?
- retinopathy: potential vision loss
- nephropathy: leading to renal failure
- peripheral neuropathy: risk of foot ulcers & amputations
- autonomic neuropathy: GI, GU, CV symptoms and sexual dysfunction
What is type 1 diabetes?
- auto immune destruction of B cells in pancreas
- usually leads to absolute insulin deficiency
- level of B cell destruction varies
- 5-10% of people who are diabetic
What is idiopathic diabetes?
- T1DM some forms have unknown causes
- Some with permanent insulinopenia and prone to ketoacidosis
- often no evidence of autoimmunity
- varying degrees of insulin deficiency
- strongly inherited
What is type 2 diabetes?
- non-insulin dependent diabetes
- insulin resistance and with relative insulin deficiency
- most common type of diabetes
- initially, do not require insulin to survive
- Most of these diabetic patients are obese and this can cause some degree of insulin resistance
What are the risks of developing type 2 diabetes?
- increasing age
- obesity
- lack of exercise
- hypertension
- women who had GDM before
What are the treatment goals for diabetes?
- control glycemia
- control of CV risk factors
- patient active participation
- improve QOL
- prevent complications
Why is self monitoring blood glucose SMBG beneficial?
- Beneficial for patients on intensive insulin regimen
- multiple doses or a continuous insulin infusion
- Should blood glucose before meals, postprandial, before sleeping, before exercise, before major efforts or when suspecting low blood glucose
What is Hb1Ac?
- Glycosylated Hb (Hb1Ac) is the average value of plasma glycemia over the previous 2-3 months in a single measurement
Hoe are patients with T1DM treated?
- most patients require multiple doses of insulin injections or continuous subcutaneous insulin injections
- they should use insulin analogues to reduce their risk of hypoglycemia
- Choice of glycemic target and drugs used varies and should be individualised to the patients
What are biguanides? MOA? Contraindications? Side effects?
- e.g. metformin
- first line medication for T2DM
MOA:
- Reduction in insulin resistance via modification of glucose metabolic pathways
- Inhibits mitochondrial glycerophosphate dehydrogenase (mGPD) → ↓ hepatic gluconeogenesis and intestinal glucose absorption
- Increases peripheral insulin sensitivity → ↑ peripheral glucose uptake and glycolysis
- Lowers postprandial and fasting blood glucose levels
- Reduces LDL, increases HDL
- most preferred way of reducing glucose in T2DM patients
- Well tolerated drug
- Contraindicated in lactation and pregnancy
When can dual therapy be used in treating diabetes?
- Hb1Ac is 9% or higher to achieve glycemic control more quickly
e.g. biguanides can be combined with sulfonylureas derivatives or SGLT-2 Inhibitors
What are sulfonylureas derivative drugs? MOA? Side effects? Contraindications?
- e.g. Glibenclamide
- oral medication which lower glucose by stimulating insulin secretion
MOA:
-Block ATP-sensitive potassium channels of the pancreatic β cells → depolarization of the cell membrane → calcium influx → insulin secretion
- Extrapancreatic effect: ↓ hepatic gluconeogenesis, ↑ peripheral insulin sensitivity
Contraindications: B blockers, obesity, severe CV comorbidities
Side effects: weight gain, risk of hypoglycemia
- others SU derivates e.g. Glipizide or Glicazide have a lower risk of hypoglycemia
What are Meglitinide drugs? MOA? Side effects? Contraindications?
- e.g. Repaglinide or Nateglinide (less effective)
- stimulate insulin secretion
- shorter half life than SU derivatives
Side effect: risk of weight gain,
What are alpha-glucosidase inhibitor drugs? MOA? Side effects? Contraindications?
- e.g. Miglitol and acarbose
- Inhibit alpha-glucosidase (a brush border enzyme expressed by intestinal epithelial cells) → delayed and ↓ intestinal glucose absorption and ↓ carbohydrate breakdown, resulting in ↓ hyperglycemia after food ingestion
- primarily lower post-prandial glucose levels without causing hypoglycemia
Contraindications: severe renal failure, IBD
Side effects: increase transaminases, flatulence, abdominal pain
What are thiazolidinedione drugs? MOA? Side effects? Contraindications?
- e.g. Pioglitazone and rosiglitazone
MOA:
- activation of the transcription factor PPARγ (peroxisome proliferator-activated receptor of gamma type in the nucleus) → ↑ transcription of genes involved in glucose and lipid metabolism → ↑ levels of adipokines such as adiponectin and insulin sensitivity → ↑ storage of fatty acids in adipocytes, ↓ products of lipid metabolism (e.g., free fatty acids) → ↓ free fatty acids in circulation → ↑ glucose utilization and ↓ hepatic glucose production
- increase insulin sensitivity and offer high glucose lowering efficacy
- TZDs increase HDL and assist in lowering CVD risks and hepatic steatohepatitis
- Side effects: fluid retention, weight gain and possible worsening of CHF and bone fracture, therefore contraindicated in CHF and severe liver failure
What are SGLT2 drugs? MOA? Side effects? Contraindications?
E.g. Dapaglifzolin, Empaglifzolin and Canaglifzolin
*renal function determines the drugs efficacy on glucose lowering
MOA:
- reversible inhibition of SGLT-2 in the proximal tubule of the kidney → ↓ glucose reabsorption in the proximal convoluted tubule of the kidney → glycosuria and polyuria
- reduce plasma glucose by enhancing urinary excretion of glucose
- decreases BP
Side effects: UTI’s, dehydrations, weight loss, orthostatic hypotension, severe diabetic ketoacidosis
Contraindications: chronic kidney disease, recurrent UTI’s
- CAUTION when combined with ACEi or ARBs
What are GLP-1 agonist drugs? MOA? Side effects? Contraindications?
- e.g. Exenatide, liraglutide
- Incretins: Endogenous hormone secreted by cells in the GI tract - potentiate insulin secretion postprandially depending on glucose
- exert effects by various G-protein coupled receptors on B cells
Incretin mimetic drugs bind to the GLP-1 receptors and are resistant to degradation by DPP-4 enzyme → ↑ insulin secretion, ↓ glucagon secretion, slow gastric emptying (↑ feeling of satiety, ↓ weight)
Side effects: GI symptoms, satiety, pancreatitis, weight loss (liraglutide shown to reduce CV events)
Contraindicated: existing GI motility dysfunction, chronic pancreatitis or family history of pancreatic tumors
What are DPP-4 inhibitor drugs? MOA? Side effects? Contraindications?
e.g. Saxagliptin, alogliptin and sitagliptin
- Increase insulin secretion and reduce glucagon secretion
MOA:
- indirectly increase the endogenous incretin effect by inhibiting the DPP-4 that breaks down GLP-1 → ↑ insulin secretion, ↓ glucagon secretion, delayed gastric emptying
- when in combo with SU derivatives, risk of hypoglycemia increases by 50%
Side effects: diarrhea/constipation, arthralgia, satiety, increased risk of pancreatitis, worsening renal function
Contraindications: liver failure or renal failure
What is the role of insulin for diabetes therapy?
- Insulin lowers glucose in a dose dependent manner over a wide range
Side effects: weight gain, glucose monitoring, constant titration for optimal dose
Different formulations: intermediate and long term
- different onset of action, duration of action and risks of hypoglycemia
What is basal insulin? Uses?
E.g. Degludec and glargine (U300 & U100)
- Degludec reduce risk of hypoglycemia
- Glargine reduces risk of nocturnal hypoglycemia (U300 compared to U100)
- Long acting insulin that covers the body’s basal metabolic insulin requirement in contrast to a bolus or prandial insulin
- preferred initial insulin formulations in patients with T2DM
