Diabetes Treatment Flashcards
what causes type 1 diabetes
results from an autoimmune response to pancreatic β-cell component(s) triggered possibly by a viral infection
what causes type 2 diabetes
hyperglycaemia may be due to
(a) impaired insulin secretion
(b) receptor and post receptor defects producing increased (insulin resistance)
(c) increased hepatic glucose production
Describe the prevalence, signs, diagnosis and treatment of LADA - Latent Autoimmune Diabetes in Adulthood
6-10% of type 2 diabetes patients
Suspect if:
- lack of metabolic syndrome features; poor glucose control with oral agents; evidence of autoimmune disease (thyroid disease and pernicious anaemia)
Diagnosis: - clinical features + anti-GAD antibodies
- If GAD +ve progress to insulin dependency more quickly
Treatment: - focus on controlling hyperglycaemia. Can develop ketoacidosis especially when insulin dependent
when are you not allowed to use HbA1c
- Do NOT use HbA1c for the diagnosis of type 1 diabetes
- Increased red cell turnover (including pregnancy!), anaemia and haemoglobinopathies
- Blood sugar levels have risen rapidly (type 1 diabetes, acute illness, drugs and raise blood sugar rapidly such as oral steroids and antipsychotics)
More sugar on it - more blood sugar
describe the treatment for type 2 diabetes
Lifestyle measures should be encouraged
If HbA1c ≥ (48mmol/mol) after a trial of lifestyle interventions start:
- Monotherapy: first-line metformin the vast majority of the time
- Alternative monotherapy if metformin not tolerated or contraindicated: depends on severity of hyperglycaemia, comorbidities, need to avoid hypoglycaemia and patient preference
If HbA1c remains ≥ 48 mmol/mol on maximum dose monotherapy, add a second drug
what is the mechanism of acton of Metformin
Several mechanisms of action have been proposed:
- reduces hepatic glucose output (activates liver AMP kinase)
- gut related glucose lowering effect
- increases liver, muscle and fat cell sensitivity to insulin - enhances peripheral glucose uptake and utilisation
at what level of serum creatinine must you stop using metformin
Stop metformin if serum creatinine increases above 150micromol/L or eGFR < 30mL/min/1.73m2
what are the Mechanisms of Sulfonylurea Action
Stimulate the release of insulin from pancreatic β cells:
- Sulfonylureas bind to SUR and block ATP-dependent K+ channels
- This reduces K+ efflux leading to:
β cell depolarization, calcium influx and secretion of insulin - May also increase the sensitivity of peripheral issues to insulin
describe the therapeutic uses of Sulfonylureas, name some of the drugs that may be antagonists to it
Of value only in the management of type 2 diabetic patients that have not demonstrated ketosis and have not responded adequately to dietary therapy and weight control
- must have functional beta cells
Therapeutic effect may be antagonized by thiazide diuretics, corticosteroids or any agents that inhibit insulin release or antagonize peripheral action
During periods of increased physical or emotional stress insulin therapy is often needed
Gliclazide, Glimepiride, Glyburide oral before meal (s)
describe Side effects of Oral Hypoglycaemics (Sulfonylureas)
May cause HYPOGLYCEAMIA:
- alcohol
- monoamine oxidase inhibitors, sulfonamides, beta blocker
- all lower blood sugar
- all enhance effects of sulfonylureas
WEIGHT GAIN, allergic reactions, pruritus, rash, hepatotoxicity and photosensitivity are possible
Hyponatraemia and water retention - non β cell effects
describe incretin hormones (GLP-1) and how they work
GLP-1 - Glucagon-Like Peptide-1
30 amino acid polypeptide
Secreted from L-cells in small intestine
Stimulated by lipids and carbohydrate
Binds to G-protein coupled receptors on B cell → insulin secretion
Degraded by dipeptidyl peptidase IV (DPP-IV) t½ 1 min
Increase insulin biosynthesis and stimulates B cell growth
Inhibits glucagon secretion, hepatic glucose output, gastric
emptying and promotes satiety
Probably x3 → x5 more potent than GIP
describe incretin hormones (GLP-1) and how they work
GLP-1 - Glucagon-Like Peptide-1
30 amino acid polypeptide
Secreted from L-cells in small intestine
Stimulated by lipids and carbohydrate
Binds to G-protein coupled receptors on cell → insulin secretion
Degraded by dipeptidyl peptidase IV (DPP-IV) t½ 1 min
Increase insulin biosynthesis and stimulates cell growth
Inhibits glucagon secretion, hepatic glucose output, gastric
emptying and promotes satiety
Probably x3 → x5 more potent than GIP
RESULT IN WEIGHT LOSS
what are some of the issues/side effects of Glucagon-like Peptide-1 Analogues
Given by subcutaneous injection (daily or weekly)
Prescribed as 2 x 3 mL prefilled pens
Can cause gastrointestinal disturbance : nausea, vomiting
Rarely associated with hypoglycaemia
Associated with increased risk of pancreatitis
? Cancer risk - pancreas / thyroid
describe the Mode of action of Gliptins (DPP IV Inhibitors)
- Inhibit depredation of incretin hormones GLP-1 and GIP by DPP4 enzymes
- this increases levels of GLP-1 and GIP leading to increased synthesis and release of insulin by pancreatic B cells.
- Glucagon secretion from pancreatic a cells is also reduced
Overall effect:
- increased glucose uptake by target tissues
- inhibit glucagon secretion
- reduce hepatic glucose output
- delay gastric emptying
- promote satiety
- reduced blood glucose levels
describe the side effects of gliptins
- nasopharyngitis (common cold)
- upper respiratory tract infection
- headache
- nausea
- peripheral oedema
Weight neutral or small weight gain, and possible risk of heart failure especially if heart/kidney disease
Caution in renal disease (see specific guidance in BNF as varies from drug to drug)
how does a SGLT2 inhibitor work
SGLT2 is highly expressed in the S1 segment of the proximal convoluted tubule were >90% of glucose re-absorption occurs
Inhibition of glucose re-absorption by blocking the action of SGLT2 will reduce the renal threshold for glucose allowing excretion of excess glucose in the urine thus lowering plasma glucose levels
Loss of calories associated ≈ 2kg weight loss with small decrease in systolic blood pressure
Empaglifozin may reduce risk of some adverse CV outcomes (cardiovascular death, heart failure (not MI))
what is the ending for Sodium-Glucose Co-transporter (SGLT2) Inhibitors
give some examples
-gliflozin
Dapagliflozin
Canagliflozin
Empagliflozin
list some adverse effects of SGLT Inhibitors
- Polyuria therefore ↑ urinary tract infections
↑Risk of acute kidney injury especially if heart failure and with drug interactions eg diuretics, ACE/ARBs, NSAID’s
Ketoacidosis (can occur without large increase in blood glucose) advise patients of potential symptoms, check ketones and to stop if significant illness / major surgery (EMA estimates risk 1:1000)
↑ risk osteoporosis / bone fracture
All Flozins(MHRA) : consider stopping if significant lower limb complications (ulcer, osteomyelitis, peripheral vascular disease) as ↑ risk amputation (mainly toe)
what are the indications for insulin therapy in type 2 diabetes
Significant hyperglycaemia at presentation
Hyperglycaemia despite maximal doses of oral agents
Decompensation (failure of an organ due to a disease)
- acute injury, stress, infection
- severe hyperglycaemia with ketonaemia and/or ketonuria
- uncontrolled weight loss
Surgery
Pregnancy
Renal disease
Allergy or serious reaction to oral agents
how do thiazolidinediones work
“Insulin Resistance Reducers”
Thiazolidinediones impact fatty acid metabolism by binding to:
Peroxisome Proliferator-activated receptors PPAR (У isoform)
Only effective in the presence of insulin
(endogenous or injected)
increase the sensitivity of tissues to insulin by recruiting glucose transporters to cell surface
overall effect:
- reduce insulin resistance
- leads to enhanced uptake of glucose/fatty acids and a reduction in blood glucose levels
what are some of the contraindications with Thiazolidinediones
Causes weight gain and potential for heart failure especially in combination with insulin
