The metabolic syndrome

THE METABOLIC
SYNDROME
Reza Nejat, M.D.
Anesthesiologist, FCCM
Former Assistant Prof., SBMU
the 4th International Congress on CCM, January 2017, Tehran, IRAN

The Metabolic Syndrome
 The Metabolic Syndrome:
 the constellation of conditions
which impose the patients to
 AtheroSclerotic
CardioVascular Diseases
(ASCVD) for two-fold
and
 Type 2 Diabetes Mellitus
(T2DM) in non-diabetics for
five-fold

 Kylin, a Swedish physician as
early as 1920s:
 The combination of
 hypertension,
 hyperglycemia
 hyperuricemia
 was noticed as an entity
with adverse outcome

 Professor Gerald M. Reaven,
from Stanford University
(1988):
 the syndrome X
 as the cluster of the conditions
which could predispose the
patients to both ASCVD and
T2DM.

 Mets and high serum
glucose level may play
significant role in
increasing the incidence
ICU-acquired infections.
 MetS increases ICU
mortality

 defined by:
 A cardiologist as
 a “state of increased coronary heart disease risk’’;
 A diabetologist as
 a ‘‘prediabetic state”;
 An endocrinologist as
 an ‘‘insulin resistance state with dyslipidemia’’;
 A hepatologist as
 ‘‘nonalcoholic fatty liver disease’’;
 A nephrologist as
 ‘‘hypertension and prehypertension.’’

 Names suggested:
 cardiometabolic syndrome,
 insulin resistance syndrome,
 the deadly quartet
 GHO Syndrome
 Adult Treatment Panel III (ATP III)
in 2001 and endorsed subsequently in
2014 by a group of experts :
 “the metabolic syndrome”

 the diagnostic criteria:
 not clustered according to prospective
studies but with the aim of:
 early identifying patients at risk
 improving the outcome of the patient
with changing of their lifestyle
1. Obesity
2. Hypertriglyceridemia
3. Hypertension
4. Glucose intolerance

 Definition of the Metabolic Syndrome
proposed by IDF:
 central obesity (Hyper-weight) plus
any two of the following 4 criteria:
a) Hyper-TG
b) Hypo-HDL cholesterol
c) Hyper-glycemia
d) Hyper-tension

 Obesity quantitatively determined by:
body mass index (BMI)
 𝑩𝑩𝑩𝑩𝑩𝑩 =
𝑾𝑾𝑾𝑾𝑾𝑾 𝑾𝑾 𝑾𝑾𝑾𝑾 𝑲𝑲𝑲𝑲
𝑯𝑯𝑯𝑯𝑯𝑯𝑯𝑯𝑯𝑯𝑯𝑯 𝒎𝒎 𝟐𝟐
 25 ≤BMI≤ 29.9
 overweight
 30 ≤BMI≤ 34.9
 obesity
 35 ≤BMI≤ 40
 morbid obesity
 Ideal BMI < 25
 the lower cuff point of ideal BMI is not defined yet.

 Central obesity or increasing the
waist circumference:
 waist circumference (European)
i. ≥ 94 cm (male),
ii. ≥80 cm (female)
 waist circumference (Asian)
i. ≥ 90 cm (male),
ii. ≥80 cm (female)
 waist circumference (USA)
i. ≥ 102 cm (male)
ii. ≥ 88 cm (female)

proposed by IDF:
 central obesity (Hyper-weight) plus any two of the
following 4 criteria:
1) Hyper-TG,
2) Hypo-HDL cholesterol,
3) Hyper-glycemia
4) Hyper-tension
 Hyper-TG
 TG ≥ 150 mg/dl (1·7 mmol/L) or
 specific treatment for this lipid
abnormality

proposed by IDF:
1) Hyper-triglyceridemia,
3) Hyper-glycemia
4) Hyper-tension
 Hypo-HDL cholesterol
 < 40 mg/dl (1·03 mmol/L) (male)
 < 50 mg/dl (1·29 mmol/L) (female)

proposed by IDF:
3) Hyper-glycemia
4) Hyper-tension
 Hyper-glycemia
 FPG≥ 100 md/dl (5.6 mmol/L) or
 previously diagnosed T2DM

proposed by IDF:
3) Hyper-glycemia
4) Hyper-tension
 Hyper-tension
 Blood pressure ≥130/85 (mmHg) or
 treatment of previously diagnosed
hypertension

 The Metabolic Syndrome criteria in
children and adolescents:
1. Obesity (visceral);
2. Hypertension;
3. Hyperinsulinemia/insulin
resistance, IGT/type 2 diabetes
mellitus;
4. Dyslipidemia (hyper-TG,
low HDL cholesterol)
 the cutoff values generally differ from study to
study and abdominal obesity is not well defined
 FAMILY Hx (>50% were over-weight with
dyslipemia)

 Has been associated with:
 essential hypertension,
 lung dysfunction due to abdominal obesity,
 chronic kidney disease,
 polycystic ovary syndrome (PCOD),
 nonalcoholic fatty liver disease (NAFLD),
 certain forms of cancer,
 obstructive sleep apnea,
 cholesterol gallstones,
 gout,
 depression,
 musculosketal disease

 Does the brain shrink as the
waist expands?
 Higher adiposity:
 frontal GM atrophy across all ages
 parietal and temporal GM atrophy
in middle and old age.

 prevalence:
 cannot be determined accurately:
 No precise definition of the metabolic
syndrome
 The cutoff point relevant to each criteria
differs in different populations
 In adults: from 10% to 40%
 In children: 2-9% in General Population
to 12-44% in overweight children
 most often seen in populations with:
 excessive caloric intake
 sedentary life style

 in IRANian population:
 more prevalent in 60-69 year age-group
than in 20-29 year age-group
 Azizi F, et al. Diabetes Res Clin Pract
(2003) 61: 29–37
 consistent with the epidemiological
findings in the USA and France
 Eckel R. H., et al. Lancet (2005) 365:
1415–28
 ranges from 10-60% depending on the
age, gender, region
 Hajian-Tilaki K. Caspian J Intern Med.
2015; 6(2): 51-61

 Clinical Presentation:
 Physical inactivity,
 Obesity,
 Ageing
 Hormonal Imbalance
 may present in variable ways:
 which component of its criteria takes the
dominant feature?
atherogenic dyslipidemia, elevated blood pressure
and dysglycemia:
 ASCVD as the clinical presentation

 Obesity
 is a true risk factor for the metabolic
syndrome; NOT THE CAUSE;
 Non-obese have metabolic risk factors,
too!!!
 took precedence among the other
contributing factors
 predisposes to insulin resistance
 Non-obese might be resistant to insulin,
too!!!
 Over-eating or over-nutrition:
 the mainstay of the syndrome

 Fat normally settles down in
adipose tissue.
 Excess of fat is distributed
ectopically in the liver and
muscles
 Over-nutrition provides
ectopic fat

 Obesity might occur:
 in the upper part of the body
 (apple-shaped body)
 in the lower part of the body
 (pear-shaped body)
 APPLE-SHAPED obesity,
predisposes to:
 the metabolic syndrome
 visceral fat more than
subcutaneous fat

 upper-body adipose tissue:
supplies ectopic fat
releasing non-esterified fatty acids
(NEFA)
 Liver
o Metabolizes these FAs,
o Re-erterifizes these Fas,
o Incorporates NEFA in VLDL as
TRIGLYSERIDES.

 Insulin in Critically ill patients (CIP)
has:
potent anti-inflammatory effects
protect against organ damage
Hyperglycemia in CIP:
glucagon, growth hormone, catecholamines,
glucocorticoids and cytokines such as IL-1,
IL-6 and TNF-α, dextrose and nutritional
support
Insulin deficiency
Insulin resistance (TRIB3 gene product)
Increased gluconeogenesis

Insulin resistance:
 reduced sensitivity to the metabolic effects
of insulin
 leads to the impaired insulin-stimulated
glucose uptake and oxidation,
uncontrolled hepatic glucose production
 increases T2DM, CVSD, NAFLD, NASH,
malignancies
Its severity may vary for sixfold??!!

Insulin resistance:
How to Dx?
 Euglycemic hyperinsulinemic clamp (the best
way)
 Homeostatic model assessment-insulin
resistance (HOMA-IR) index and
𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻 − 𝐼𝐼 𝐼𝐼 = [𝐼𝐼𝐼𝐼𝐼𝐼𝐼𝐼𝐼𝐼𝐼𝐼𝐼𝐼
𝑈𝑈
𝑚𝑚𝑚𝑚
× 𝐵𝐵𝐵𝐵
𝑚𝑚𝑚𝑚
𝑑𝑑𝑑𝑑
]/405
 Quantitative insulin sensitivity check
index(QUICKI)
𝑄𝑄𝑄𝑄𝑄𝑄𝑄𝑄 𝑄𝑄𝑄𝑄 = 1/[log 𝐼𝐼𝐼𝐼𝐼𝐼𝐼𝐼𝐼𝐼𝐼𝐼𝐼𝐼
𝑈𝑈
𝑚𝑚𝑚𝑚
+ log 𝐵𝐵𝐵𝐵(
𝑚𝑚𝑚𝑚
𝑑𝑑𝑑𝑑
)]

White Adipose Tissue:
 extensive communicative system with
other tissues and organs.
 Adipocyte direct signal to other
tissues:
skeletal muscle
the adrenal cortex.
 a distinct cross-talk between white
adipocytes and the brain through
leptin and the sympathetic nervous
system.

 White Adipose Tissue
 is not just a fuel storage
 is an endocrine organ
 secrets several major hormones (SECRETOMES)
 In a autocrine/paracrine fashion
 proteins implicated in neuroendocrine and immunity
 ADIPOCYTOKINES
 ADIPOKINOMES
 ADIPOKINES
 Leptin
 Adiponectin

 SECRETOMES:
 adipokines together with lipid moieties
released, such as fatty acids and
prostaglandins,
 ADIPOKINES (over fifty):
 classical cytokines (TNFa, IL-6,
IL-8),
 growth factors [transforming
growth factor-β (TGF-β),
FGF21]
 proteins of the alternative
complement system (adipsin,
acylation-stimulating protein)

 ADIPOKINES, involved in :
 vascular hemostasis (plasminogen activator
inhibitor-1 (PAI-1), tissue factor),
 the regulation of blood pressure
(angiotensinogen, mineralocorticoids)
 lipid metabolism (retinol-binding protein,
cholesteryl ester transfer protein),
 glucose homeostasis (adiponectin, possibly
resistin) and
 angiogenesis (vascular endothelial growth
factor; VEGF),
 acute-phase and stress reactants (haptoglobin,
metallothionein)

 Adiponectine:
 synthesised only in adipose
tissue
 With anti-atherogenic and anti-
inflammatory effects
 With inhibitory implication on
phagocytic activity and TNFα
production
 falls in obesity and T2DM
 inversely related to insulin
resistance

 TNF-α in obesity, involved in:
 insulin resistance,
 chronic low-grade inflammatory state
 has inhibitory effect on the insulin
receptor signaling pathway
 stimulate CRP release from the liver;
 CRP level rises with BMI and falls with
weight loss
 Secretion of nerve growth factor (NGF)
associated with atherosclerosis and
wound healing
 Apoptosis
 Production of IL-6 and Haptoglobulin

IL-6 is expressed in and
secreted by adipocytes:
has local actions within WAT
released into the circulation
 IL-6 expression in WAT:
elevated in obesity and insulin
resistance
conveying information from
adipocytes to the hypothalamus
regulating balance of energy

 TGF-β, of pleiotropic
growth factor family with:
 immuno-regulatory properties
 malignancies,
 autoimmune disorders,
 susceptibility to opportunistic
infections and
 fibrotic complications in
chronic inflammatory
conditions

 PAI-1:
 synthesis in WAT is raised in obesity
 SAA:
 major acute-phase reactants
 pro-inflammatory and anti-
inflammatory
 CRP:
 WAT a major player in the raised
circulating levels of CRP in obesity,
 through the indirect route of
adipocyte-derived IL-6

 Leptin:
 Secreted by adipose tissue
 Crosses BBB readily
 Signals to the brain of the
status of body energy stores
 Inhibit food intake
 Leptin deficiency and resistance

 rezanejat.com
 icuaticu.com
 2icuedu.com

EKG

The metabolic syndrome

Recommandé

Recommandé

Contenu connexe

Tendances

Tendances (20)

Similaire à The metabolic syndrome

Similaire à The metabolic syndrome (20)

Plus de Reza Nejat, M.D., FCCM

Plus de Reza Nejat, M.D., FCCM (15)

Dernier

Dernier (20)

The metabolic syndrome