Metabolic syndrome and diabetes

Question 1

Metabolic Syndrome (Met-S)

Answer 1

Metabolic Syndrome is a highly complex and multifactorial disorder, which shares several common underlying mechanisms, including:
– Fat accumulation (ectopic fat e.g. visceral/intra-abdominal fat)
– Impaired insulin sensitivity (i.e. insulin resistance), and
– Low-grade chronic systemic inflammation (the pro-inflammatory state).

Met-S is rapidly increasing in prevalence worldwide as a consequence of the continued obesity ‘‘epidemic’’

Question 2

The pathophysiological effects of Met-S

Answer 2

• are diverse; clinically diseases :
  – Type 2 diabetes (T2d),
  – Non-alcoholic Fatty Liver Diseases (NAFLD),
  – Cardiovascular diseases (CVD)

Question 3

World Health Organization Criteria - Definitions of Met-S

Answer 3

• Impaired Glucose Regulation/Insulin Resistance
• Abdominal/Central Obesity
• Hypertriglycemia
• Low Levels of HDL Cholesterol
• Raised Blood Pressure
• Microalbuminuria

Question 4

Fat accumulation & Met-S

Answer 4

• Adipose tissue the largest endocrine organ
• Adipocytes are the primary cell type of adipose tissue
• Adipose tissue is a highly active metabolic and endocrine organ.
– The primary site of storage for excess energy
– An endocrine organ - synthesizing a number of biologically active compounds that regulate metabolic homeostasis.

Question 5

(2) Insulin resistance & Met-S

Answer 5

• Insulin signaling regulates glucose, lipid, and energy homeostasis.
• Insulin has 3 major target tissues: skeletal muscle, liver and adipose tissue.
– Insulinreceptors(IR)areoverexpressedinthecellsofthesetissues,
• Insulin resistance is defined where insulin levels are normal or elevated but
target cells become less sensitive to insulin. Consequences:
– After a meal – hyperglycemia & compensatory hyperinsulinaemia

Question 6

(3) Low-grade chronic systemic inflammation & MetS

Answer 6

• A chronic state of inflammation appears to be a central mechanism underlying the pathophysiology of MetS

Question 7

Circulating fats (lipids and lipoproteins)

Answer 7

• Lipoproteins - carry lipids in the bloodstream – Protein component called apolipoprotein
• Very low density lipoproteins (VLDL) – Known as “bad cholesterol”
• Intermediate density lipoproteins (IDL)
• Low density lipoproteins (LDL)
• High density lipoproteins (HDL)
– Known as “good cholesterol”

** Elevated lipids can lead to cardiovascular disease such as atherosclerosis

Question 8

The role lipoproteins in atherosclerosis

Answer 8

• Atherosclerotic lesions initiate with endothelial cell dysfunction causing modification of apolipoproteins containing LDL, VLDL

Question 9

Endocrine Pancreas

Answer 9

• Pancreas secretes hormones produced in pancreatic islets:
• Insulin (produced by β cells)
– Lowers blood glucose levels
• Glucagon (produced by α cells)
– Increases blood glucose levels
• Somatostatin (produced by δ cells) – inhibits insulin and glucagon secretion

Question 10

Diabetes mellitus (DM)

Answer 10

• Due to lack of insulin secretion or action or both
• Characterised by chronic hyperglycaemia
• Main types of diabetes:
• • Type 1, Type 2, Gestational (women during pregnancy)

Question 11

Impaired insulin signalling

Type 1

Answer 11

autoimmune disease > no insulin > high blood glucose levels > complications with heart and liver

• person is unable to produce insulin that delivers sugar from their bloodstream into their cells
• most common form of diabetes in children , only 5% of diabetes in adults
• rapid onset, defect: destruction of beta-cells,

Question 12

Impaired insulin signalling

Type 2

Answer 12

life style and genetics >
1. insulin deficiency > type 2 diabetes > vascular disease
or
2. obesity and metabolic stress > vascular disease

represent 90-95% in adults

• dual defect of resistance to the action of insulin, combined with an inability to make enough insulin to overcome resistance
• slow onset, normal or icnreased insulin secretion, defet: insulin resistance

Question 13

gastational diabetes

Answer 13

3 - 8 % of pregnant women

due to hormones from pregnancy or shortage of insulin

Question 14

Diabetes - Long term effects

Answer 14

• Diabetics - shorter life expectancy than the general population – Depends on the patients ability to control circulating glucose levels.

Question 15

damage:

Answer 15

• 1. Vascular damage: damage to large blood vessels supplying heart and vein
- glycation and fat deposits build up
* diabetic retinopathy: Renal failure and blindness
• Neuropathies
– impaired blood flow damages nerves of the CNS and PNS - damage to small blood vessels supply kidney > increased BP and fluid retention

• DIABETIC NEPHROPATHY - CHRONIC LOSS OF KIDNEY FUNCTION
• renal failure largest cause of death

Question 16

Diabetes – Treatment*

Answer 16

based on managing blood glucose