Diabetes Flashcards
DIabetes is characterised by…
…increased urine production.
Two types of diabetes:
Diabetes mellitus and insipidus
Whats diabetes mellitus characterised by?
1) persistent glucosuria
- Excretion of glucose in urine
- Due to hyperglycemia (high blood [glucose])
Diabetes insipidus: caused by …
…inadequate secretion of vasopressin (AVP) by the pituitary gland or failure of kidneys to respond to AVP
AVP produced when we are…
…dehydrated causing the kidneys to absorb more water leading to concentrated urine to be produced.
Lack of AVP leads to …
…very dilute urine production and extreme thirst (polydipsia)
Whats type 2 diabetes due to?
due to insulin resistance &/or inadequate insulin production
Whats type 1 diabetes due to?
Type 1: β-cells of endocrine pancreas destroyed
Whats gestational diabetes?
Hormonal changes and insulin resistance due to pregnancy
Whats diabetes MODY?
- Maturity Onset Diabetes of the Young
- No associated with obesity, but inherited due to string risk factors
Whats double diabetes?
Has both type I and II
Whats steroid diabetes?
due to taking steroid anti-inflammatory drugs
Whats secondary diabetes?
due to another medical condition
Only type I and II diabetes mellitus are …
…well defined
Type I diabetes mellitus Characterised by …
…absolute deficiency of insulin secretion
Causative element of type 1 diabetes?
No one definitive causative element, but there is involvement of:
- Autoimmune components involved in the destruction of pancreatic islet cells
- Genetics
- Exposure to viruses and other environmental factors
Type I diabetes mellitus risk factors?
- Family history: E.g. parent or sibling
- Genetics: Variants of HLA-DQA1, HLA-DQB1 and HLA-DRB1 genes
- Geography: T1DM incidence increases travelling away from the equator
- Age: Two noticeable peaks in children – a) 4 - 7 years old, b) 10 - 14 years old
Type II diabetes mellitus Caused by a combination of:
- Resistance to insulin action
- Inadequate compensatory insulin secretory response
In inadequate compensatory insulin secretory response (type 2 diabetes):
- Hyperglycemia sufficient to cause pathologic and functional changes in various target tissues exists, but without clinical symptoms – asymptomatic
- Asymptomatic hyperglycemia may be present for a long period of time before diabetes is detected
The world health organisation defines several other causes which are:
1) The world health organisation defines several other causes
- 7.3.1 Genetic defects of beta-cell function
- 7.3.2 Genetic defects in insulin action
- 7.3.3 Diseases of the exocrine pancreas
- 7.3.4 Endocrinopathies
- 7.3.5 Drug- or chemical-induced diabetes
- 7.3.6 Infections
- 7.3.7 Uncommon but specific forms of immune-mediated diabetes mellitus
- 7.3.8 Other genetic syndromes sometimes associated with diabetes
2) Lead to classification of type 3(a-h) diabetes mellitus by some
In 2008, Monte and Wands, put forward a proposal that Alzheimer’s disease could be termed …
…type 3 diabetes.
In 2008, Monte and Wands, put forward a proposal that Alzheimer’s disease could be termed type 3 diabetes.
Their reasoning is based on the observation that …
…insulin resistance within the brain is feature of Alzheimer’s disease.
Diabetes is a group of …
…metabolic diseases, characterized by hyperglycemia due to defects in:
- Insulin secretion
- Insulin action
- Insulin secretion AND insulin action
Chronic diabetes hyperglycemia results in long-term damage, dysfunction and failure of organs, e.g.:
Eyes
Kidneys
Nerves
Heart
Blood vessels
Pathogenic processes involved in the development of diabetes include
- Autoimmune destruction of the pancreatic b-cells that results in insulin deficiency
- Abnormalities resulting in resistance to insulin action
Deficient insulin action on target tissues results in …
…abnormalities in metabolism of macronutrients such as carbohydrates, fat, and protein.
Deficient insulin action results from:
- Inadequate insulin secretion, and/or
- Diminished tissue responses to insulin
Impaired insulin secretion and defects in insulin action frequently …
…coexist in patients.
- It is unclear which abnormality, if either alone, is the primary cause of the resultant hyperglycemia
Symptoms of marked hyperglycemia include:
- Polyuria
- Polydipsia
- Weight loss (sometimes with polyphagia - excessive eating or appetite)
- Blurred vision
WHats polyuria?
production of abnormally large volumes of dilute urine
Whats polydipsia?
increased thirst
Chronic hyperglycemia may also be accompanied by:
- Impaired growth
- Susceptibility to certain infections
Acute, life-threatening consequences of uncontrolled diabetes are hyperglycemia with:
- Ketoacidosis
- Non-ketotic hyperosmolar syndrome (very high blood glucose levels without keto acidosis causes osmotic problems)
Whats ketoacidosis ?
acidification of the blood due to high levels of ketones
WHats Non-ketotic hyperosmolar syndrome?
very high blood glucose levels without keto acidosis causing osmotic problems
Long-term complications of diabetes include:
1) Retinopathy with potential loss of vision
2) Nephropathy leading to renal failure
3) Peripheral neuropathy with risk of foot ulcers, amputations, and Charcot joints
4) Autonomic neuropathy causing symptoms in the following systems:
- Gastrointestinal
- Genitourinary (and sexual dysfunction)
- Cardiovascular
Diabetic patients also have an increased incidence of:
- Atherosclerotic CVD
- Peripheral arterial disease (PAD)
- Cerebrovascular disease
- Hypertension
- Abnormalities of lipoprotein metabolism
- Alzheimer’s disease
Patients at increased risk of developing inadequate compensatory insulin secretory response can be identified by:
1) Autoimmune pathologic process occurring in the pancreatic islets
2) Markers of the immune destruction of the β-cell include:
- Islet cell autoantibodies
- Autoantibodies to insulin
- Autoantibodies to GAD (GAD65)
- Autoantibodies to tyrosine phosphatases (IA-2 and IA-2b)
3) Genetic markers (HLA genes)
During the asymptomatic period abnormal carbohydrate metabolism can be evidenced by measuring:
- Fasting plasma glucose levels
- After a challenge with an oral glucose load
- A1c levels (haemoglobin-bound glucose)
Haemoglobin A1c reveals …
…average levels ofblood sugar over previous 2 – 3 months
A1c ranges:
- Healthy patients: 4 - 5.6%
- Asymptomatic or pre-diabetic patients: 5.7 - 6.4 %
- Diabetics: > 6.5%
Haemoglobin-bound Glucose Also referred to as:
- HbA1c test
- Glycated haemoglobin test
- Glycohaemoglobin test
The rate carbohydrates enter the blood from ingested food is termed its …
…glycaemic index (GI)
Conclusions of Ojo O, Ojo O, Adebowale F, Wang X. (2018) The Effect of Dietary Glycaemic Index on Glycaemia in Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Nutrients. 10(3):373. ?
“The low-GI diet is more effective in controlling glycated haemoglobin and fasting blood glucose compared with a higher-GI diet or control in patients with type 2 diabetes.”
In the presence of insulin, Glut4 vesicles…
…fuse with the plasma membrane
Glut4 allows…
…glucose to enter the cell.
Insulin inhibits…
…lipolysis (fat degradation) and promotes fat storage
Glucagon stimulates …
…lipolysis and release of fatty acids & glycerol
Insulin insensitivity thus promotes …
…fat storage
Hormone-sensitive lipase initiates …
…lipolysis
Non-modifiable causes of type 2 diabetes?
Native American, Pima Indians, Hispanic or Black race (genetic & environmental)
Family history of type II Diabetes (genetic predisposition)
Ageing
Polycystic ovary syndrome
Modifiable causes of type 2 diabetes?
Polycystic ovary syndrome
Obesity (approx. 90% of obese people develop Type II Diabetes)
Fat distribution (visceral vs. subcutaneous)
Sedentary lifestyle
Smoking
High levels of chronic stress and anxiety (cortisol & adrenalin)
What are general risk factors in type 2 diabetes mellitus?
- Obesity & body composition
- Waist circumference – fat distribution
- Social Class
- Gestational diabetes
- Age
- Genetics / Race
- Non-modifiable risk factors
Behavioural Risk Factors of type 2 diabetes?
- Low levels of physical activity & sedentary lifestyle
- Central adiposity due to increased (chronic) stress levels
- Adrenaline & cortisol are Hyper-glycaemic hormones
- The omentum stores fat and has cortisol receptors. Cortisol leads to fat accumulation
Diabetes Has a Greater Impact on CVD in…
…Women Than in Men.
Causative Dietary Elements of type 2 diabetes mellitus?
- High levels of high GI foods – High glycaemic load
- Poor intake of essential fatty acids / Reduced n-3:n-6 ratio
- Consumption of high levels of saturated fat and trans fats
- Poor soluble fibre intake – Non-starch polysaccharide (soluble fibre)
- Deficiencies of many micronutrients (copper, iodine, manganese, molybdenum, zinc, etc.)
- Poor vegetable and fruit intake - Low levels of antioxidants (e.g. carotenoids, flavonoids, tocopherols)
- Deficiency in antioxidant vitamins and minerals
- Barbecued and chargrilled food
- High salt intake (or Na+/K+ imbalance)
- Excessive alcohol
Symptoms of type 2 diabetes mellitus on the eyes?
Blurred vision (no glucose in eyes)
Symptoms of type 2 diabetes mellitus on the breath?
- Smell of nail polish remover
Symptoms of type 2 diabetes mellitus on the skin?
- Dry, itchy skin
- Poor wound healing
Central effects of diabetes mellitus?
- Polydipsia
- Polyphagia
- Lethargy
Symptoms of type 2 diabetes mellitus on the gastric?
- Nausea
- Vomiting
- Abdominal pain
Symptoms of type 2 diabetes mellitus on the urinary tract?
- Polyuria
- Glycosuria
Main Clinical Features of type 2 diabetes mellitus?
- Rapid weight loss
- Excessive hunger (polyphagia)
- Fatigue
- Glucosuria (excretion of glucose into the urine)
- Frequent micturation (polyuria) and nocturia
- Dehydration and thirst - polydipsia
- Blurred vision
- Deep sighing breathing (Kussmaul breathing)
- Eventually – ketosis -> confusion -> coma
Pathophysiology of hyperinsulinemia and hyperglycaemia?
1) Hyperinsulinemia & hyperglycaemia
2) Atherogenic dyslipidaemia
3) Increased lipogenesis in arterial tissue & atherosclerosis
4) Stimulated Na+ reabsorption in distal kidney tubules & Alteration in Na+/K+ distribution
5) Ketogenesis
6) Protein glycation (Glycated or glycosylated haemoglobin)
7) Inflammation
8) Decreased Plasma antioxidants
9) Increased Plasma fibrinogen
10) Tissue damage - Diabetic retinopathy, nephropathy and neuropathy
Whats Hyperinsulinemia?
A condition where the bodys cells become less responsive to the effects of insulin, requiring the pancreas to produce more insulin to compensate.
Developmental Pathway for Diabetes?
1) Chronic glucose overload chronic hyperglycaemia
2) Hyperinsulinemia
3) IR downregulation (muscle and adipose tissue)
4) Lack of activation – decreased IR density on cell membrane – insulin resistance
5) Glucose retained in the blood
6) Hyperglycaemia – glucose intolerance
7) Diabetes
What happens in Atherogenic Dyslipidaemia?
High LDL & triglycerides
Low HDL
High LDL = high risk
> 3.0 mmol/L
High HDL = low risk
> 1.1 mmol/L
In Atherogenic Dyslipidaemia, there is increased…
…lipogenesis in arterial tissue and proliferation of smooth muscle cells (atheroma) = atherosclerosis
Stimulated Na+ Reabsorption in Distal Kidney Tubules increases the risk of …
…Hypertension
Na+-glucose linked transporter (SGLT) are also termed…
…Na+-dependent Glucose Co-transporters
What happens in Na+-glucose linked transporter (SGLT) in diabetes?
The kidney automatically tries to reabsorb the glucose, and in the process reabsorbs sodium too. Both increase blood pressure.
Process of ketogenesis?
1) Insulin resistance adipocytes and myocytes starved of glucose
2) Signal for adipocytes to increase lipolysis
3) Lipolysis releases FFA + glycerol (FA can be used as an alternate fuel by several tissues including the muscles, but NOT by the brain)
4) FAs increase in the blood
5) FAs increasingly utilised by mitochondria - large quantities of Acetyl CoA
6) Liver is overloaded and Acetyl CoA spills over into metabolic pathways acetone, acetoacetic acid and β-hydroxybutyric acid ketone bodies in blood and urine
7) Breath smell of acetone (nail polish remover)
8) Blood pH change
What is Protein Glycation ?
Non-enzymatic reaction that adds a carbohydrate group to a protein or peptide.
What happens in Protein Glycation (Glycated or Glycosylated Haemoglobin) chronically?
excess glucose binds to collagen and other proteins (Hb)
Protein glycation is a process proportionate to…
…the level of hyperglycaemia
What are AGEs?
Advanced Glycation End Products
Common features of mild chronic inflammation?
Metabolic syndrome, Obesity , Diabetes
Conclusions of the study titled “Metabolic syndrome: a comprehensive perspective based on interactions between obesity, diabetes, and inflammation. Circulation”?
“Individuals with the highest concentrations of inflammatory markers are found to go on to develop type II diabetes; twice as likely as those without elevation of inflammatory markers”
Conclusions of the study titled “The Effects of a Low GI Diet on Cardiometabolic and Inflammatory Parameters in Patients with Type 2 and Gestational Diabetes: A Systematic Review and Meta-Analysis of Randomised Controlled Trials. Nutrients”?
“With respect to the inflammatory parameters, the low GI diet significantly decreased interleukin–6 in patients with type 2 diabetes compared to the higher GI diet”.
What enzymes are involved in Reduced Levels of Plasma Antioxidant Protection?
1) Superoxide dismutase
2) Catalase
3) Glutathione peroxidase
Increased Plasma Fibrinogen results in…
…High blood viscosity
What are people with Increased Plasma Fibrinogen susceptible to?
Susceptibility to vascular damage & thrombosis & Cerebral Vascular Accident (aka Stroke)
Risk of Increased Plasma Fibrinogen raised by…
- Obesity
- Hypertension
- Hyperglycaemia
- Hypercholesterolemia
- Some oral contraceptives
Neuropathy is a …
…chronic and acute sensory disorder
Types of Tissue Damage - Microvascular Disease?
1) Diabetic Retinopathy
2) Neuropathy
3) Autonomic neuropathy
3) Nephropathy
Symptoms of Tissue Damage - Microvascular Disease?
Painful cramps, muscle weakness, numbness to touch and vibration, spontaneous tingling or burning pain
How does Tissue Damage - Microvascular Disease progress?
Loss of feeling -> ulceration -> infection -> amputation
Whats Nephropathy?
Kidney tubule damage
- Diabetic Glomerulosclerosis (scarring)
Key concepts in setting glycaemic goals?
- A1C is the primary target for glycemic control
- Goals should be individualized based on various factors.
Glycemic goals should be individualised based on…
- duration of diabetes
- age/life expectancy
- Comorbid conditions
- Known CVD or advanced microvascular complications
- Hypoglycaemia unawareness
- Individual patient considerations
More or less stringent glycemic goals may be appropriate for…
…invididual patients
Postprandial glucose may be targeted if A1C goals are not met despite …
… reaching pre-prandial glucose goals.
Glycaemic Recommendations for Diabetic Adults - A1C ?
A1C = <7.0%
Glycaemic Recommendations for Diabetic Adults - Pre-prandial capillary plasma glucose ?
Pre-prandial capillary plasma glucose = 70 - 130 mg/dl (3.9 - 7.2 mmol/l)
Glycaemic Recommendations for Diabetic Adults - Peak post-prandial capillary plasma glucose ?
<180 mg/dl (<10.0 mmol/l)
How is type II diabetes prevented?
- Increase physical activity & increase muscle mass (not only for weight loss but to improve blood glucose control)
- Decrease adiposity lifestyle changes
- Balancing macronutrients
- Low glycaemic index / load diet
- Increase natural dietary antioxidants
- Omega-6 / omega-3 ratio (No higher than 5:1)
- Saturated fat
- Salt intake (Na+/K+ balance)
- Alcohol
