Endocrine

The Era of Hips & Waists

Hypertension in Metabolic syndrome

Common risk factors for chronic diseases

Deaths from 4 chronic diseases

Deaths from all other causes
50% of all deaths

3 risk factors

Tobacco

Poor diet
Lack of exercice

4 chronic diseases

Cancer

Type 2 diabetes
Chronic respiratory disease
Cardiovascular
Oxford Health Alliance 2003

Obesity, Type 2 Diabetes, Hypertension or Dyslipidemia

Relative risk
Waist circumference (cm)
Adapted from Lee ZSK et al. Obes Rev 2002; 3: 173-82 andKo GT et al. Int J Obes Relat Metab Disord 1997; 21: 995-1001
0

History of MS

1923 - Kylin first to describe the clustering of hypertension, hyperglycemia, hyperuricemia
1936 - Himsworth first reported Insulin insensitivity in diabetics
1965 - Yalow and Berson developed insulin assay and correlated insulin levels & glucose lowering effects in resistant and non-resistant individuals

1988 - Reaven in his Banting lecture at the ADA meeting coined the term Syndrome X and brought into focus the clustering of features of Metabolic Syndrome
Reaven now prefers the name, Insulin-Resistance Syndrome - feels insulin resistance is the common denominator for Metabolic Syndrome

Metabolic Syndrome

Etiology – not fully elucidated
Insulin Resistance
Acquired causes
• Overweight and central (visceral) obesity
• Physical inactivity, aging, ethnicity
• High CHO diets (>60%)
Proinflammatory state, hormones
Poly Genic causes


INSULIN RESISTANCE - MECHANISMS
Pre receptor ( abnormal insulin or insulin
antibodies)
Receptor ( decreased receptor number or affinity)
Postreceptor (abnormal signal transduction and phosphorylation)
Glucose transporter ( decreased GLUT 4 molecule)

INSULIN RESISTANCE & HYPERTENSION

More than 50 % of hypertensives are found to be Insulin Resistant and Hyperinsulinemic.

IR and Hyperinsulinemia have been

documented to be present even in lean
Hypertensives who are not Diabetic

MS Clustering of Components:

Hypertension: BP. > 140/90
Dyslipidemia: TG > 150 mg/ dL ( 1.7 mmol/L )
HDL- C < 35 mg/ dL (0.9 mmol/L)
Obesity (central): BMI > 30 kg/M2
Waist girth > 94 cm (37 inch)
Waist/Hip ratio > 0.9
Impaired Glucose Handling: IR , IGT or DM
FPG > 110 mg/dL (6.1mmol/L)
2hr.PG >200 mg/dL(11.1mmol/L)
Microalbuninuria (WHO)


Necessary Criteria to Make Diagnosis
WHO:
Impaired G handling + 2 other criteria.
Also requires microalbuminuria - Albumen/ creatinine ratio >30 mg/gm creatinine
NCEP/ATP III:
Require three or more of the five criteria

IDF(2006):

Abdominal obesity plus two other components: elevated BP, low HDL, elevated TG, or impaired fasting glucose

Measurement of Waist

Normal

Visceral Adiposity

Courtesy of Wilfred Y. Fujimoto, MD.

Visceral Fat Distribution

IDF Waist Circumference

MS
2 times increase risk of HT
3 times increase risk of CHD or stroke
5 times increase risk of DM
Chronic liver disease
Increase risk of more than 60 diseases

Resulting Clinical Conditions:

Type 2 diabetes
Essential hypertension
Polycystic ovary syndrome (PCOS)
Nonalcoholic fatty liver disease
Sleep apnea
Cardiovascular Disease (MI, PVD, Stroke)
Cancer (Breast, Prostate, Colorectal, Liver)


Hypertension in MS:
IDF:
BP >130/85 or on Rx for previously Dxed hypertension
WHO:
BP >140/90
NCEP ATP III:
BP >130/80

Obesity Effects on Blood Pressure

Mean DBP (mmHg)

Clock time (hours)
Intra-abdominal (Visceral) Fat Area Tertiles and 24-hour Ambulatory Blood Pressure and Pulse Rate in Chinese Type 2 Diabetic Patients
Clock time (hours)
Mean HR (bpm)
Clock time (hours)
Mean SBP (mmHg)
DBP: diastolic blood pressure
HR: heart rate
SBP: systolic blood pressure

Copyright © 1997 American Diabetes Association

Adapted from Diabetes Care ®, Vol. 20, 1997; 1854-8
Reprinted with permission from The American Diabetes Association

Metabolic variables in white coat (WC) and sustained (SUST) borderline hypertension Tecumseh study
Julius et al., Hypertension 16, 1990. Tecumseh

NORMAL WC SUST

N=621
N=28
N=34

n.s.

p<.001
26
22
18
14
Insulin Level


10

p<.001

Hypertension is a very prominent feature of the metabolic syndrome, present in up to 85% of patients.

Metabolic Syndrome & Hypertension

Randomized prospective study in Italy with >1700 people with HTN (mean 155/95) & no CVD, followed for a mean of 4 years
During follow up, 162 pts developed CV events, a total of 593 pts had metabolic syndrome using NCEP guidelines
Those with MS had an almost double CV event rate 3.23 vs 1.76per 100pt years.

Insulin Resistance and Hypertension Mechanisms

Hyperinsulinemia
Produces renal sodium retention.
Stimulates Sympathetic Nervous activity
Vascular smooth muscle hypertrophy (mitogenic action of insulin)
cytokines and other lipokines
Augmentation of the pressor and
aldosterone response to angiotensin II
Endothelial dysfunction and decreased production of NO


Results of current long term outcome studies support the hemodynamic concept of insulin
resistance in hypertension

HYPOTHESIS

If in addition to cardiovascular responses, the metabolic responses were also decreased in hypertension, the patient’s ability to dissipate calories would be diminished and they would gain more weight.

BP Control - How Important?

MRFIT and Framingham Heart Studies:
Conclusively proved the increased risk of CVD with long-term sustained hypertension
Demonstrated a 10 year risk of cardiovascular disease in treated patients vs non-treated patients to be 0.40.
40% reduction in stroke with control of HTN

therapy

a multi-target approach based on the assessment of the overall cardiovascular risk should be applied;
A-non-pharmacological therapy; sodium restriction, alcohol and calorie restriction, smoking cessation, weight reduction, and increase physical activity.

Antihypertensive Medications:

Angiotensin -converting Enzyme Inhibitors (ACEI)
Angiotensin II Receptor (ARB) Blockers
Combination with Thiazides, Calcium Channel Blockers, Cardioselective Beta Blockers
Target BP: <130/80

Fit vs. Fat: Can you be both?

Overweight and obese people who are fit are less likely to die prematurely than unfit people who are lean (Lee, CD, et al., Am J Clin Nutr 1999; 69:373-380)
Highly Fit men with 2 or 3 risk factors had about the same mortality risk as Low Fit men with no risk (Blair, SN, et al., JAMA 1996; 276: 205-210)
Low Fitness is as significant a risk factor for premature death as smoking, high blood pressure, diabetes, and high blood cholesterol, regardless of weight ( Barlow et al., Int J Obes Metab Disord, 19(suppl 4):41, 1995 and Wei et al., JAMA, 282: 1547, 1999)










-For preventive purposes

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