LECTURES COURSE BMW 3010
THE METABOLIC SYNDROME
Course Content
HC 1 Introduction lecture 3
HC 2 Energy balance in the metabolic syndrome 9
HC 3 Regulation and dysregulation of metabolic homeostasis by the liver 11
HC 4 Muscle as a metabolic organ in development, progression and treatment of the 18
metabolic syndrome
HC 5 The role of macrophages in the development of the metabolic syndrome and 25
atherosclerosis
HC 6 Pathophysiology of adipose tissue in the metabolic syndrome 30
HC 7 The gastro-intestinal tract and the pancreas in the development and treatment of 38
the metabolic syndrome
HC 8 Surgical interventions in the treatment of the metabolic syndrome 44
,HC 1 Introduction lecture
The metabolic syndrome
Cluster of metabolic disorders ‘cluster’ in knowledge required
Multiple organ disorder
Understanding inter-organ relationships is key
Nutritional, exercise and pharmaceutical treatment approaches
From syndrome X to metabolic syndrome. Syndrome X can be:
Resistance to insulin-stimulated glucose uptake (common)
Glucose intolerance
Hyperinsulemia (compensatory effect)
Increased very-low-density lipoprotein triglyceride
Decreased high-density lipoprotein cholesterol
Hypertension (patients are at increased risk of CVD; this risk is not blunted upon anti-
hypertensive treatment)
o Clustering of consequences of insulin resistance may contribute to hypertension and
CVD
There is a progressive decline in insulin mediated glucose uptake in subjects (prone to/with) type 2
diabetes. The glucose uptake decreases when there is an impaired glucose tolerance (IGT) or in non-
insulin dependent diabetes mellitus (NIDDM).
In normal glucose tolerant subjects, the insulin mediated glucose uptake is increased and there is a
low fasting plasma glucose. In patients with an impaired glucose tolerance, the insulin mediated
glucose uptake is reduced, but the fasting blood glucose is still low. In patients with NIDDM, the
insulin mediated glucose uptake is low and the fasting plasma glucose is high.
Essentially, there is no relationship between plasma glucose and insulin stimulated glucose
disposal
Insulin resistance of adipose tissue:
o progressive increase in insulin concentration
OGTT (oral glucose tolerance test):
o no effect of antihypertensive treatment
Fructose-induced insulin resistance (in rats):
o Blood glucose and insulin levels after 3 hours of infusion of glucose with low insulin
are lower compared to blood glucose and insulin levels after 3 hours of infusion with
fructose
Reduced insulin sensitivity associates with:
Hyperinsulinemia
Reduced glucose tolerance
Hypertriglyceridemia
Reduced HDL
Hypertension
Note:
In 1988 the most findings were associations (GLUT4, the insulin regulatable glucose
transporter has been discovered in 1987)
Experimental interventions are largely from animal work
It is unclear what triggers the reduction in insulin sensitivity
2
, It is unclear why combined factors associate with hypertension
It is unclear why the cardiovascular risk is increased
No major emphasis on inter-organ relationship
No major role for the body mass is implicated
3
THE METABOLIC SYNDROME
Course Content
HC 1 Introduction lecture 3
HC 2 Energy balance in the metabolic syndrome 9
HC 3 Regulation and dysregulation of metabolic homeostasis by the liver 11
HC 4 Muscle as a metabolic organ in development, progression and treatment of the 18
metabolic syndrome
HC 5 The role of macrophages in the development of the metabolic syndrome and 25
atherosclerosis
HC 6 Pathophysiology of adipose tissue in the metabolic syndrome 30
HC 7 The gastro-intestinal tract and the pancreas in the development and treatment of 38
the metabolic syndrome
HC 8 Surgical interventions in the treatment of the metabolic syndrome 44
,HC 1 Introduction lecture
The metabolic syndrome
Cluster of metabolic disorders ‘cluster’ in knowledge required
Multiple organ disorder
Understanding inter-organ relationships is key
Nutritional, exercise and pharmaceutical treatment approaches
From syndrome X to metabolic syndrome. Syndrome X can be:
Resistance to insulin-stimulated glucose uptake (common)
Glucose intolerance
Hyperinsulemia (compensatory effect)
Increased very-low-density lipoprotein triglyceride
Decreased high-density lipoprotein cholesterol
Hypertension (patients are at increased risk of CVD; this risk is not blunted upon anti-
hypertensive treatment)
o Clustering of consequences of insulin resistance may contribute to hypertension and
CVD
There is a progressive decline in insulin mediated glucose uptake in subjects (prone to/with) type 2
diabetes. The glucose uptake decreases when there is an impaired glucose tolerance (IGT) or in non-
insulin dependent diabetes mellitus (NIDDM).
In normal glucose tolerant subjects, the insulin mediated glucose uptake is increased and there is a
low fasting plasma glucose. In patients with an impaired glucose tolerance, the insulin mediated
glucose uptake is reduced, but the fasting blood glucose is still low. In patients with NIDDM, the
insulin mediated glucose uptake is low and the fasting plasma glucose is high.
Essentially, there is no relationship between plasma glucose and insulin stimulated glucose
disposal
Insulin resistance of adipose tissue:
o progressive increase in insulin concentration
OGTT (oral glucose tolerance test):
o no effect of antihypertensive treatment
Fructose-induced insulin resistance (in rats):
o Blood glucose and insulin levels after 3 hours of infusion of glucose with low insulin
are lower compared to blood glucose and insulin levels after 3 hours of infusion with
fructose
Reduced insulin sensitivity associates with:
Hyperinsulinemia
Reduced glucose tolerance
Hypertriglyceridemia
Reduced HDL
Hypertension
Note:
In 1988 the most findings were associations (GLUT4, the insulin regulatable glucose
transporter has been discovered in 1987)
Experimental interventions are largely from animal work
It is unclear what triggers the reduction in insulin sensitivity
2
, It is unclear why combined factors associate with hypertension
It is unclear why the cardiovascular risk is increased
No major emphasis on inter-organ relationship
No major role for the body mass is implicated
3
