Lecture 26: Metabolic syndrome and diabetes Flashcards
What is insulin resistance?
For a given concentration of insulin there is a subnormal glucose response. (ie. high insulin levels with normal or high glucose)
Pre receptor, receptor or post receptor (mostly post - inside cell)
Very common and preceeds diabetes by years being associated with :
- Obesity, Type 2 diabetes, Endocrine disorders (eg. cushings, acromegaly) and metabolic syndrome.
How to recognize insulin resistance in a patient?
- Metabolic syndrome cluster - central obesity with two of : hypertension, abn. glucose, high triglycerides (due to uncontrolled lipolysis) or low HDL (due to insulin resistance in liver)
- Acanthosis nigricans - Darker regions due to Insulin-like GF
- PCOS - women with PCOS are insulin resistant (normally overweight and present with hirsutism and acne)
What causes Insulin resistance?
- Inherited factors
- Environmental factors - intrauterine (SGA and fatter in adult = high risk. Normal and normal = lower risk) , Obesity
Increased visceral fat (bigger not more cells) and therfore stored triglyceride -> large adipocytes that are resistant to the ability of insulin to supress lipolysis. Increased lipolysis leads to increased release of non-esterfied fatty acids (NEFA) and glycerol.
NEFA and glycerol + inflammatory cytokines released by visceral adipose tissue (eg. TNFa, IL6) aggravate insulin resistance in muscle and LIVER.- liver starts producing more and more glucose and become cirrhosed
May also cause lipotoxicity in the beta cells
Adiponectin and/or resistin implications in insulin resistance?
Adiponectin and resistin may provide a link between obesity and insulin resistance.
Adiponectin deficiency may play a role in development of insulin resistance and type 2 diabetes
Resistin is secreted by adipocytes of obese mice and decreases adipocyte glucose uptake.
Concequences of Insulin resistance?
Glucose:
- Hepatic glucose output not supressed
- Insulin mediated glucose uptake in muscles (GLUT 4) in reduced
- thus, only hyperinsulinaemia can maintain normale levels
Fat
- Metabolic - rise in FFA, triglycerides (perpetuating cycle)
- Hormones - Adipocytokines
Concequences of glucose and other things rising?
Glucose rising causes toxicity to beta cells
FFA causes lipotoxixity in beta cell, lover and muscles
Results in:
- Poor first phase insulin release leadin gto post prandial hyperglycaemia
- Alpha cell dysregulation and hyperglucagonaemia
- beta cell dysfunction is a critical step in the pathogenesis of type 2 diabetes (decreased cell mass - genetic or maternal as well as decresed function - less pulses, lipotogluotoxicity or incretin dysfunction)
The metabolic syndrome?
What is diabetes mellitus?
A metabolic disorder characterised by the presence of hyperglycaemia due to defective insulin secretion, insulin action or both
or
disorder of premature widespread athersclerosis with hyperglycaemia as an associated feature
HbA1c?
HbA0 - bulk standard Haemaglobin
A1a b and c
a and b are normal but in low amounts
c - takes on glucose (4-6% of Hb). Therefore the higher the HbA1c is a good monitoring tool and diagnstic tool
Classification of Diabetes?
Type 1
- immune-mediates B cell destruction
- idiopathic
Type 2
- obesity-related, insulin resistance
Genetic
Pancreatic disease
Endocrinopathies
Drugs Gestational
Concequences of diabetes?
Mircovascular complications
- retinopathy - silent, leading cause of blindness
- peripheral neuropathy (mono and autonomic) - burning, numbness, ulcers and foot infections
- Nephropathy - proteinuria > reduction of GFR. Commonest cause of ESRF with high mortality
Macrovascular complications
- IHD (70% of deaths in diabetes)
- PVD - further complicates peripheral neuropathy
- CVA (cerebrovascular attack)
Management of diabetes?
- lifestyle factors of diet and exercise paramount
- medication to control glucose
- Insulin in type 1 and about 50% of T2
- Metformin
- Sulphonylurea
- Insulin incretin therapy
- Attention to BP, lipids, smoking etc
