Multifactor approach in diabetes

Salman Razvi
Jakarta
th
12 February 2015

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)

Global cardiometabolic risk*

* working definition

Gelfand EV et al, 2006; Vasudevan AR et al, 2005

International Diabetes Federation

(IDF) Consensus Definition 2005
The new IDF definition focusses on abdominal obesity rather than
insulin resistance

Fat Topography In Type 2

Diabetic Subjects

Intramuscular
Subcutaneous

Intrahepatic
Intraabdominal

FFA*
TNF-alpha*
Leptin*
IL-6 (CRP)*
Tissue Factor*
PAI-1*
Angiotensinogen*

Abdominal obesity and increased

risk of cardiovascular events
The HOPE study

Adjusted relative risk

Waist
circumference (cm):

1.4

Tertile 1

Men
<95

Women
<87

Tertile 2
Tertile 3

95103
>103

8798
>98

1.29

0.8

1.27

1.17

1.2
1

1.16
1

CVD death

1.35

1.14
1

MI

All-cause deaths

Adjusted for BMI, age, smoking, sex, CVD disease, DM, HDL-cholesterol, total-C;
CVD: cardiovascular disease; MI: myocardial infarction; BMI: body mass index;
DM: diabetes mellitus; HDL: high-density lipoprotein cholesterol
Dagenais GR et al, 2005

Abdominal obesity increases the

risk of developing type 2 diabetes
24

Relative risk

20
16
12
8
4
0
<71

7175.9

7681

81.186

86.191 91.196.3

>96.3

Waist circumference (cm)

Carey VJ et al, 1997

Abdominal obesity is linked to an

increased risk of coronary heart
disease
Waist circumference has been shown to be independently
associated with increased age-adjusted risk of CHD, even after
adjusting for BMI and other cardiovascular risk factors
3.0

Relative risk

2.5

p for trend = 0.007

2.31

2.44

2.06

2.0
1.5

1.27

1.0

0.5
0.0
<69.8

69.8<74.2

74.2<79.2 79.2<86.3

86.3<139.7

Quintiles of waist circumference (cm)

CHD: coronary heart disease; BMI: body mass index
Rexrode KM et al, 1998

Central obesity: a driving force for

cardiovascular disease & diabetes
Front

Back

Balzac by Rodin

Insulin Resistance: Associated

Conditions

Linked Metabolic Abnormalities:

Impaired glucose handling/ insulin resistance
Atherogenic dyslipidemia
Endothelial dysfunction
Prothrombotic state
Hemodynamic changes
Proinflammatory state
Excess ovarian testosterone production
Sleep-disordered breathing

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)

Multiple Risk Factor Management

Obesity
Glucose Intolerance
Insulin Resistance
Lipid Disorders
Hypertension
Goals: Minimize Risk of Type 2 Diabetes and
Cardiovascular Disease

Glucose Abnormalities:
IDF:

FPG >100 mg/dL (5.6 mmol. L) or previously

diagnosed type 2 diabetes
(ADA: FBS >100 mg/dL [ 5.6 mmol/L ])

Hypertension:
IDF:

BP >130/85 or on Rx for previously

diagnosed hypertension

Lifestyle modification

Diet
Exercise
Weight loss
Smoking cessation

If a 1% reduction in HbA1c is achieved,

you could expect a reduction in risk
of:
21% for any diabetes-related
endpoint
37% for microvascular
complications
14% for myocardial infarction

However, compliance is poor and most patients will require

oral pharmacotherapy within a few years of diagnosis
Stratton IM et al. BMJ 2000; 321: 405412.

BP Control - How Important?

Goal: BP.<130/80
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
Precedes literature on Metabolic Syndrome

Lipid Control - How Important?

Goals: HDL >40 mg% (>1.1 mmol /l)
LDL <100 mg/dL (<3.0 mmol /l)
TG <150 mg% (<1.7 mmol /l)
Multiple major studies show 24 - 37% reductions
in cardiovascular disease risk with use of statins
and fibrates in the control of hyperlipidemia.

Substantial residual cardiovascular risk in

statin-treated patients
The MRC/BHF Heart Protection Study

% patients

30

Placebo
Statin

20

Risk reduction=24%
(p<0.0001)

19.8% of statin-treated
patients had a major
cardiovascular event
by 5 years

10

0
0

3
4
Year of follow-up

Heart Protection Study Collaborative Group, 2002

A Critical Look at the Metabolic Syndrome

Lifestyle
The advice remains to treat individual risk factors
when present & to prescribe therapeutic lifestyle
changes & weight management for obese
patients with multiple risk factors.

Recommendations for treatment

Primary management for the Metabolic Syndrome is healthy lifestyle
promotion. This includes:
moderate calorie restriction (to achieve a 5-10% loss of body weight in
the first year)
moderate increases in physical activity
change dietary composition to reduce saturated fat and total intake,
increase fibre and, if appropriate, reduce salt intake.

Management of the Metabolic Syndrome

Appropriate & aggressive therapy is essential
for reducing patient risk of cardiovascular disease
Lifestyle measures should be the first action
Pharmacotherapy should have beneficial effects on

Glucose intolerance/diabetes
Obesity
Hypertension
Dyslipidaemia

Ideally, treatment should address all of the components of the

syndrome and not the individual components