Pathophysiology of Type 2 Diabetes and Lifestyle Management Flashcards
How is glucose stored in the body?
- In liver and muscle as glycogen
* Fat (longer-term storage)
Mechanism of insulin release?
- Glucose is transported into the pancreatic β-cell by GLUT2 and is metabolised, to increase ATP conc.
- ATP binds to the KATP channel and causes closure; K+ can no longer enter the cell so depolarisation occurs, opening the Ca2+ channel
- Intracellular Ca2+ conc. increases and this stimulates insulin within vesicles to be released
Pathophysiology of hyperglycaemia?
Insulin resistance and β-cell dysfunction is caused by: • Diabetes genes • Adipokines • Inflammation • Hyperglycaemia • Free fatty acids
Pancreas produces more insulin which:
• Regulates lipolysis from fat; also regulates glucose production within the liver, which increases blood glucose
• Stimulates glucose uptake into muscle
Core physiological defects in T2DM?
- Insulin resistance
* β-cell dysfunction
Explain insulin resistance
Insulin binds to receptor triggering production of glucose transport proteins to allow glucose to enter the cell
In insulin resistance, the receptor is less responsive to the insulin molecule and thus less glucose enters the cell; results in accumulation of glucose in the blood
Cause of insulin resistance?
- Ectopic fat accumulation and increase FFA (free fatty acid) circulation; this decreases glucose transport
- Increased inflammatory mediators (CRP)
These both cause inhibition of insulin via serine kinases (responsible for phosphorylation of insulin receptor substrate-1, IRS-1); this results in reduced insulin-stimulated-glycogen synthesis due to reduced glucose transport
What is insulin resistance assoc. with?
- Intra-abdominal obesity and inactivity
- Genetics and aging
- Medications
- Smoking
- Fetal malnutrition
- Endothelial disease and dysfunction, PCOS (Polycystic Ovary Syndrome), microalbuminaemia, T2DM, hypertension, non-alcoholic fatty liver disease, dyslipidaemia and macrovascular disease
What is β-cell dysfunction?
Reduced ability of β-cells to secrete insulin in response to hyperglycaemia
Initially the β-cells compensate for insulin resistance by increaseing insulin production (i.e: there is impaired glucose tolerance); but pancreatic burnout occurs and insulin production decreases with a rise in blood glucose levels
Consequences of insulin resistance?
- Glucotoxicity (hyperglycaemia)
- Lipotoxicity (elevated FFA and triglycerides)
Both cause declining β-cell function
Describe β-cell function at the time of diagnosis of T2DM
β-cell dysfunction is already significant (approx. 50% of β-cell function is lost)
What is reversal T2DM?
Normalisation of β-cell function in assoc. with decreased pancreas and liver triacylglycerol
This is possible with strict calorie control to ~800 calories per day; there can be normal fat levels in the pancreas and near-normal post-prandial insulin production
Presence of insulin resistance pre-diagnosis?
Early defect in T2DM, preceding it by up to 20 years
General weight of people with T2DM?
90% are overweight/obese; some are not, but this is atypical
Apple vs pear shaped risk?
Apple-shaped patients (weight in the a central distribution) have a higher risk of T2DM and CV disease, compared to pear-shaped patients (weight on the hips)
Apple-shaped people have more intra-abdominal fat, i.e: around their organs as well as subcutaneously
What is central-adiposity assoc. with?
- High BP
- High triglycerides
- Low HDL
- Insulin resistance
i.e: the metabolic syndrome
Why are T2DM complications often present at diagnosis?
Many patients have T2DM 9-12 years pre-diagnosis and chronic damage may occur in this time and presentation with life-threatening metabolic problems can occur, e.g:
• Hyperglycaemia, hyperosmolar, non-ketotic coma (HONK)
Other complications: • Retinopathy • Neuropathy • Nephropathy • Erectile dysfunction
Typical features of TD2M presentation?
Age (uncommon <50 years and certainly <40 years; may still occur but atypical)
Obesity is common
Other metabolic features:
• Dyslipidaemia
• Hypertension
Often a strong FH
Differential diagnoses to consider alongside T2DM?
Red flags for:
• T1DM (young age, usually ~12 years old)
• Pancreatic disease
• LADA (similar presentation to T1DM but later in life, usually 35-40 years)
• Medication-induced
How to determine if it is safe to treat T2DM with lifestyle changes alone?
Consider:
• HbA1c level
• Osmotic symptoms
• Weight loss
Therapy staircase of T2DM?
- Diet and exercise (lifestyle changes)
- Oral monotherapy
- Oral combination
- Injectable (exogenous insulin) and oral combination
Presenting features of T2DM?
Insidious onset of symptoms, which may include: • Thirst (polydipsia) • Polyuria • Fatigue • Thrush
There is NO weight loss, generally, and most people are obese
Conditions in the FH that may indicate T2DM?
FH of T2DM or gestation diabetes
Conditions in the PMH that may indicate T2DM?
- Gestational diabetes
- PCOS (Polycystic Ovarian Syndrome)
- Pancreatitis
- Cystic Fibrosis or myotonic dystrophy
Drugs that can cause T2DM or signs that indicate it?
Steroids, statins, thiazides
SH to consider in potential T2DM presentation?
Alcohol intake (consider pancreatic issues, e.g: pancreatitis)
Smoking
Signs on examination of T2DM?
Acanthosis nigricans (thickening and hyperpigmentation of the skin, often in skin folds, due to INSULIN RESISTANCE)
No signs of other endocrine disease, e.g: Cushing’s disease
Lifestyle advice to help control T2DM?
- Weight loss (improves survival and reduces risk of diabetes-related death)
- Exercise
- Smoking cessation
- Improve diet
Relationship between obesity and relative risk in T2DM of mortality?
As BMI increase, past 25, relative risk of mortality increases
However, this can be adjusted, e.g: in the South-East Asian population, BMI cut-off can be 22
Consequences of obesity?
Increased risk of diabetes and CV disease
Guidelines for physical activity in older adults?
Some physical activity is better than none and more activity provides greater health benefits
Older adults at risk of falls should incorporate physical activity to improve balance and coordination on at least 2 days of the week
Factors that affect self-management of T2DM?
- Health literacy, education/knowledge
- Motivation, e.g: wearable technology, like pedometers, apps, activity monitors
- Competing priorities, time
- Other health issues
- Social and mood problems
Methods of aiding patient self-management?
- Education, e.g: structured education programmes (should be offered to all T2DM patients)
- Motivational interviewing
- Personal info sharing
- Behaviour changing
Low health literacy levels are assoc. with?
- Increased rate of chronic condition, e.g: diabetes, obesity and hypertension
- Poor disease Mx, poor glycaemic control,
- Complications
- Hypoglycaemia
- Higher risk of death
What is House of Care for diabetes?
Motivation interviewing that involves: • Goal setting, e.g: target HbA1c • Behaviour change • Information sharing • Education
