Week 8: Diabetes Flashcards
normal reaction to glucose
When you eat, your body breaks food down into glucose. Glucose is a type if sugar that is your body’s main energy source.
- As blood glucose rises, the body sends signals to the pancreas, which releases insulin
- Insulin (B-cells) binds to insulin receptors, unlocking the cell so glucose can pass into it (bringing GLUT 4 receptors to the surface of cells)
- Most glucose is used for energy right away
pancreatic islet cells
beta- insulin
alpha- glucagon
why does blood glucose rise in diabetes
2 fundamental principle mechanisms
- Inability to produce insulin due to beta cell failure
- Insulin production adequate but insulin resistance prevents insulin working effectively and invariably linked to obesity
types of diabetes related to blood glucose
- Type 1 and 2
- Gestation
- Prediabetes
normal blood glucose rnage
3.3-7 mmol/l
diagnostic criteria of diabetes based on
-
Diagnosis
- Symptoms (retinopathy, neuropathy etc) plus one abnormal result or
- Two abnormal results at different times (at least week)
-
Glucose levels
- Fasting >7.0 mmol/l and/or
- 2 hours after 75g glucose >11.1 mmol/l
- Hba1c >6.5%
fasting blood glucose above
7.0 mmol/l
Oral glucose tolerance test above
11.1 mmol/l 2 hours after 75g
Hba1c above
6.5%
General management of DM
*
- Glycaemic control
- Diet and exercise
- Oral hypoglycaemic drugs
- Insulins
- Limiting cardiovascular risk by targeting risk factors
type 1 diabetes
- Absolute insulin requirement
- Pathophysiology: Autoimmune destruction of beta cells leading to absolute insulin deficiency
- Associated with other autoimmune disease- e.g. thyroid
- Causes
- Not well understood
- Genetic predisposition
- Virus’
presentation of type 1 diabetes
- <30 years old usually
- Rapid onset (usually weeks)
- Weight loss
- Polyuria
- Polydipsia
- Ketosis
- BMI below 35 usually
- Late presentation- may be vomiting due to ketoacidosis
diagnosis of type 1 diabetes
- Elevated plasma glucose- HbA1C, FBG, random plasma glucose of higher than 11.1mmol/l
- Presence of autoantibodies
- Islet cells- GAD65
- Presence of ketones is an indication for immediate insulin therapy
target Hba1c for T1DM
A target HbA1c level of 48 mmol/mol (6.5%) or lower, to minimize the risk of long-term vascular complications
management of T1DM
- Insulin therapy (exogenous)
- Numerous devices subcut injection
- Intermediates
- Rapid
- Mixtures
- Analogues
- Numerous devices subcut injection
- Pt education
- Exercise
- Diet
- Glucose monitoring with BM
- Regular HbA1ctesting and complications screening
types of insulin and example names
type 2 diabetes mellitus
relative insulin deficiency
Background
- Pancreas loses ability to produce insulin or insulin production is adequate but insulin resistance prevents insulin working effectively
- Cause- environmental
- Obesity (central obesity)
- Muscle and liver fat deposition
- Physical inactivity
- Genetic influence
RF for T2Dm
- Prediabetes
- High BMI
- Genetically inclined
- Physically inactive
- Have had gestational diabetes
- African American, Indian,
presentation of T2DM
- >45 yo usually (getting younger)
- Onset more gradual
- Thirst
- Polyuria
- Tiredness
- Infections
- Change in vision
diagnosis of T2DM
- Based on clinical features
- HbA1c of 48mmol/mol (6.5%) or more
- FPG of 7 mmol/l or more in presence of symptoms of diabetes
- Random plasma glucose of 11.1 mmol/l in presence of symptoms or signs of diabetes
- If pt has no symptoms do a repeat testing of Hba1c
management of T2DM
- Lifestyle- weight loss
- Non-insulin therapies (oral hypoglycaemics)
- Biguanide i.e. metformin
- Sulphonylureas
- GLP1 analogues
- SGLT2
- Anti-obesity drugs- orlistat
- Insulin
- Patient education
pharmacological management fo t2DM
if patient doesnt tolerate metformin what is the next step
modified release metformin
when is metformin offered
metformin is still first-line and should be offered if the HbA1c rises to 48 mmol/mol (6.5%)* on lifestyle interventions
if whilst taking emtformin the HbA1c increases to 58 mmol/mol (7.5%) then a second drug should be added from the following list:
- sulfonylureas
- glicazide
- gliptin
- saxagliptin
- pioglitazone
- SGLT-2 inhibitor
- canagliflozin
if despite double therapy the HbA1c rises to, or remains above 58 mmol/mol (7.5%) then triple therapy with one of the following combinations should be offered:
- metformin + gliptin + sulfonylurea
- metformin + pioglitazone + sulfonylurea
- metformin + sulfonylurea + SGLT-2 inhibitor
- metformin + pioglitazone + SGLT-2 inhibitor
- OR insulin therapy should be considered
Criteria for glucagon-like peptide1 (GLP1) mimetic (e.g. exenatide)
- if triple therapy is not effective, not tolerated or contraindicated then NICE advise that we consider combination therapy with metformin, a sulfonylurea and a glucagon-like peptide1 (GLP1) mimetic if:
- BMI >= 35 kg/m² and specific psychological or other medical problems associated with obesity or
- BMI < 35 kg/m² and for whom insulin therapy would have significant occupational implications or weight loss would benefit other significant obesity-related comorbidities
- only continue if there is a reduction of at least 11 mmol/mol [1.0%] in HbA1c and a weight loss of at least 3% of initial body weight in 6 months
Cannot tolerate metformin or contraindicated
- if the HbA1c rises to 48 mmol/mol (6.5%) on lifestyle interventions, consider one of the following:
- sulfonylurea
- gliptin
- pioglitazone
- if the HbA1c has risen to 58 mmol/mol (7.5%) then a one of the following combinations should be used:
- gliptin + pioglitazone
- gliptin + sulfonylurea
- pioglitazone + sulfonylurea
- if despite this the HbA1c rises to, or remains above 58 mmol/mol (7.5%) then consider insulin therapy
Managing risk factors of diabetes
- Regular BM testing, Hba1C
- Reduce weight / BMI
- Physical activity
- DIET
- Managing CVD risk
- Statins for high cholesterol (atorvostatin)
- Antihypertensives
- Screening for diabetes complications
antihypertensives in diabetics
ACE inhibitors or angiotensin II receptor blockers (ARB) are first-line
- an ARB is preferred if the patient has a black African or African–Caribbean family origin
Screening in T2DM
- HbA1C monitored every 3-6 months
- 12 monthly check with diabetic nurse
- Kidney function
- U and E
- Creatinine
- Albumin
- Diabetic eye screening
- Foot ulcer clinics
- Cholesterol screening
- BP
- Kidney function
routine delivery of insulin
- HbA1C monitored every 3-6 months
- 12 monthly check with diabetic nurse
- Kidney function
- U and E
- Creatinine
- Albumin
- Diabetic eye screening
- Foot ulcer clinics
- Cholesterol screening
- BP
- Kidney function
MOA of insulin
- Insulin binds to insulin receptor
- Causes cascade of events which causes GLUT4 receptors to translocate from the cytoplasm to the membrane
- GLUT4 increases uptake of glucose into the cell lowering blood glucose
Adverse drug response of insulin
- Hypoglycaemia
- Lipodystrophy
- Lipohypertrophy or
- lipoatrophy
contradiction of insulin
- renal impairment- hypoglycaemia risk
drug-drug interaction of insulin
- dose needs increasing with systemic steroids (steroids increase blood glucose)
- caution with other hypoglycaemic agents
basal bolus dosin
A common dosing schedule for young active TIDM patients which provides some flexibility if adherence is good
- Basal- long acting e.g. glargine
- Given once a day
- Bolus- rapid acting e.g. aspart
- Given before meals
sulphonylureas
glicazides
- stimulates pancreatic insulin secretion
- beware of hypoglycaemia
- weight gain
- PO
biguanides
metformin
- reduces hepatic glucose output- stop glucoseneogenesis
- no risk of hypoglycaemia
- suppresses appetite
- PO
thiazolidinediones (glitazones)
pioglitazone
- PPAR agonist
- enhanced insulin sensitivity
- risk of hypoglycaemia
- increase weight
Dipeptidyl peptidase-5 (DPP-4) inhibitors (gliptins)
saxagliptin, sitagliptin
- prevent breakdown of incretins- incretins promote insulin secretion and suppress glucagon release
- no risk of hypoglycaemia
- reduces appetite
SGLT-2 inhibitors
canagliflozin
- reduces glucose reabsorption via sodium glucose channel
- no risk of hypoglycaemia
- helps decrease weight
glucagon-like peptide-1 (GLP1) receptor agonists (incretin mimetic)
exenatide, liraglutide
- mimics incretin- increases glucose-dependant synthesis of insulin
- no risk of hypoglycaemia
- increased satiety
- Sub cut injection
Macrovascular complications of DM
- Cerebrovascular
- stroke
- Cardiovascular
- MI
- Angina
- Peripheral vascular disease
- Intermittent claudication
- Gangrene
- Peripheral neuropathy leading to
- Diabetic foot ulceration
- Charcot’s foot
Microvascular complications
- Retinopathy
- Nephropathy
- Diabetic nephropathy
- Neuropathy
- Erectile dysfunction
- Foot ulceration
acute complications
ketoacidosis and HHNS
diabetic ketoacidosis triad
- glucose > 11 mmol/l or known diabetes mellitus
- pH < 7.3
- ketones > 3 mmol/l or urine ketones ++ on dipstick
