SR. CONSULTANT PHYSICIAN
DIABETOLOGIST
MAHARAJA AGRASEN
HOSPITAL, P.BAGH, DELHI
NORTH DELHI DIABETES
CENTRE, ROHINI, DELHI
The prevalence of Type-2 Diabetes mellitus is
rising to epidemic proportions. DM is feared most for morbidity & mortality
associated with its chronic complications.
Since the introduction of new oral agents, insulin
devices & better patient care fortunately both Type-I & Type-2
diabetics now enjoy significant longivity but unfortunately with that we are
witnessing rising pool of micro & macro vascular complications. This is
going to put enormous financial & manpower burden on the total health care
system & medical faternity since the cost of treating complications happens
to be even more than five times then treating diabetes mellitus itself.
Although all diabetic patients are prone to
microvascular complications namely – Diabetic Neuropathy, nephropathy,
retinopathy, which can impede their quality of life but it is macrovascular
complications which most increase morbidity and mortality1
Vascular complications are one of the most serious
consequences of diabetes and are responsible for most of the excess mortality
observed in diabetic patients. It is likely that all blood vessels both small
& large are abnormal in diabetic patients with long standing disease.
Although there is a generalized microangiopathy but
microvascular blood vessel in retina, renal glomeruli & microvessels of
large nerves seem to have significant pathology.
Similarly, of the large vessels, the arteries of
the lower limbs are particularly affected, although the carotid & coronary
vessels are also involved. Statistics for vascular disease in patients with
Type-2 diabetes are alarming. The risk of coronary artery disease or stroke is
increased 2-4 folds compared with general population, and the risk of
peripheral vascular disease is increased four times 2,3
Diabetic microvascular complications can occur in
patients with either Type-1 or Type-2 diabetes despite improvements in
management of glucose, blood pressure and lipid levels.
As many as 37% of patients with diabetes suffer at
least one microvascular complication, and at least 13% have more than one4
In a study of 3010 diabetics by Ramachandran A.5
, the prevalence of microvascular complications was – Retinopathy – 23.7%,
Nephropathy-5.5%, Neuropathy-27.5% & Prevalence of CHD-11.4% & PVD was
4%.
In our own study from North Delhi Diabetes Centre6 comprising 720 type-2 diabetics, Retinopathy
was seen in 21.2%, Micoralbuminuria in 41%, Peripheral Neuropathy in 15.3%, CAD
in 7% & PVD was seen in 7.4% of patients.
Screening for microvascular complications
There is no perfect way to predict which patients
with diabetes will develop microvascular complications, nor the severity and at
what stage will microvascular complications shall manifest 7,8
Infect, many studies have established beyond doubt
that about 20% patients do have atleast one or more microvascular &
macrovascular complications at the time of diagnosis of Type-2 Diabetes 9
(UKPDS).
In our own study10 the prevalence of
various microvascular and macrovascular complications at onset was – NPDR 10%,
peripheral neuropathy – 20%, microalbuminuria.- 16%
1.
Diabetic Nephropathy Screening –
As per ADA Clinical
Practice Recommendations 2006 – perform an annual test for the presence of
microalbuminuria in Type-1 diabetic patients with diabetes duration of > 5
years and in all type-2 diabetic patients, starting at diagnosis and during
pregnancy 11
Serum creatinine should be
measured at time of diagnosis and at least annually for the estimation of
glomerular filtration rate (GFR) in all adults with diabetes regardless of the
degree of Urine albumin excretion12,13
2.
Diabetic Retinopathy Screening –
ADA recommends that adults
& adolescents with type-1 diabetes should have an initial dilated and
comprehensive eye examination by an ophthalmologist or optometrist within 3-5
years after the onset of diabetes14
Patients with type-2 diabetes
should have an initial dilated and comprehensive eye examination shortly after
the diagnosis of diabetes and subsequently every one year. Less frequent
examination (every 2-3 years) may be considered in the setting of a normal eye
exam & more frequent exam will be required if retinopathy is progressing15
However, women who are
planning pregnancy or who have become pregnant should have a comprehensive eye
examination during 1st Trimester with close follow up during
pregnancy & should be counseled on the risk of development or progression
of diabetic retinopathy16
3.
Neuropathy Screening
Patients with diabetes
should be screened for Distal symmetric polyneuropathy (DPN) at diagnosis using
tests such as pinprick sensation, temperature and vibration perception (Using a
128 Hz tunning fork), 10 gm monofilament pressure sensation at the dorsal
surface of both great toes, just proximal to the nail bed and ankle reflexes17,18
Combinations of more than one test have > 87% sensitivity in detecting DPN. Loss of 10 gm monofilament perception and reduced vibration perception predict foot ulcers.
A minimum of one clinical
test should be carried out annually, and the use of two tests will increase
diagnostic ability.
Focal & multifocal neuropathy assessment requires clinical
examination in the area related to the neurological symptoms. Similarly
screening for autonomic neuropathy (AN) should be instituted at diagnosis of
Type-2 diabetes. Cardiovascular autonomic neuropathy may be indicated by
resting tachycardia > 100 bpm, orthostasis (a fall in systolic blood
pressure > 20 mm upon standing) or other disturbances in autonomic nervous
system function involving the skin, pupils or gastrointestinal and
genitourinary systems19.
Special
electrophysiological testing for DPN & AN is rarely needed & may not
effect management and outcomes.
Once the diagnosis of DPN
is established a referral for preventive specialist or podiatrist for special footwear is
appropriate.
Early recognition and
appropriate management of neuropathy in diabetics is important because upto 50%
of DPN may be asymptomatic and these patients are at risk of insensate injury
to their feet. Moreover, autonomic neuropathy may involve every system in the
body and especially cardiovascular autonomic neuropathy causes substantial
morbidity and mortality.
1.
Foot Screening
A comprehensive foot
examination should be performed at diagnosis and subsequently annually using a
monoflament, tunning fork, palpation of foot vessels and a visual examination
for skin colour, nail changes, callous or foot ulcers20 Consider
obtaining an ankle brachial index (ABI), as many patients with PVD or lower
arterial disease (LEAD) are asymptomatic, moreover, presense of PVD or LAED
should be taken as a corrugator marker for presence of simultaneous Coronary
artery disease (CAD)21
A multidisciplinary
approach is recommended for patients with diabetic foot or foot ulcers and all
patients with significant PVD, foot ulcers or neuroischaemic foot should be
referred to foot specialist or podiatrist because foot ulceration and ultimate
amputation are most common consequences of diabetic neuropathy and
neuroischemic foot contributing to major morbidity and mortality in
patients with diabetes22.
The risk of ulcers or amputations is significantly
increased in people who have have diabetes > 10 yrs, are male, have poor
glycemic control or have cardiovascular, retinal or renal complications.
2.
CVD
CVD is the major cause of
mortality for individuals with diabetes. It is also a major contributor to
morbidity and direct and indirect costs of diabetes.
Type-2 Diabetes itself is
an independent risk factor for macrovascular disease, and its common
co-existing conditions (e.g. Hypertension and dyslipidemia) are also risk
factors.23.
Various studies have shown
the efficacy of reducing cardiovascular risk factors in preventing or slowing
CVD.
I)
Blood pressure should be measured at every routine diabetes visit.
Patients found to have systolic blood pressure > 130 mmHg or diastolic blood
pressure > 80 mmHg should get it confirmed on a separate day & if found
Hypertensive should be treated to a blood pressure < 130/80 mmHg 24
II)
Dyslipidaemia – In Type-2 Diabetics a detailed lipid profile should be
done at onset & subsequently annually at least & more often at times to
achieve the following goals
LDL < 100 mg/dl
HDL > 50 mg/dl
Tgs <
150 mg/dl
Lifestyle modification
focusing on the reduction of saturated fats & cholesterol intake, weight
loss (if indicated), and increased physical activitly has been shown to improve
the lipid profile in patients with diabetes.
Lipid management aimed at
lowering LDL cholesterol, raising HDL cholesterol, and lowering Tgs has been
shown to reduce macrovasular disease and mortality in patients with Type-2
diabetes, particularly in those who have had prior cardiovascular events.25
III)
CHD Screening.
In asymptomatic patients
consider a risk factor evaluation at least annually to stratify patients by 10
yr. risk and treat risk factors accordingly.26 These risk factors
include dyslipidaemia, hypertension, smoking, a positive family history of CAD
& the presence of micro or macroalbuminuria.
Candidates for a
diagnostic cardiac stress test include those with
a)
Typical or atypical cardiac symptoms
and
b)
An abnormal resting ECG.
The screeing of asymptomatic patients remains controversial although studies have demonstrated that a significant percentage of patients with diabetes who have no symptoms of CAD have abnormal stress tests, either by ECG or echo and nuclear perfusion imaging27
It is also demonstrated
that patients with silent myocardial ischaemia have a poorer prognosis than
those with normal stress tests. Their risk is further accentuated if cardiac
autonomic neuropathy coexists.28 Approximately 1 in 5 will have an
abnormal test & >1 in 15 will have major abnormality.
However, more information
is needed concerning prognosis, and the value of early intervention (invasive
or noninvasive) before wide spread screening is recommended as there are no
large controlled prospective trials with adequate control groups to shed light
on approach towards diabetic patients with silent ischaemia.
A recent report indicated
that only 37% of adults with diagnosed diabetes achieved on HbAic < 7%, only
36% had a blood pressure < 130/80 mmHg and just 48% had a cholesterol <
200 mg/dl. Most distressing was that only 7.3% diabetic subjects achieved all
three treatment goals.29
Both DCCT30
& UKPDS31 trials have proven that at any given time about 35% à 65% diabetic patients
having hyperglycemia shall develop some or the other microvascular or
macrovascular complication with conventional treatment.
Several lines of evidence
suggest that the increased risk of vascular disease in diabetes starts about 10
years earlier – possibly even from birth or even from womb.
As many as 50% of patients
with newly diagnosed Type-2 Diabetes already have evidence of some
macrovascular disease,32 hence, inspite of great strides in the
management of diabetes death rate continues to rise largely from vascular
disease33 Hence, message is very clear that having type-2 diabetes
is like having had an MI in the past. So diabetics are considered to be CAD
equivalent.
Hence, approach to a
patient with diabetes requires a multidisciplinary approach with special
emphasis on early screening for various vascular complications first at the
time of diagnosis & subsequently at least once a year to retard or check
the further propagation of complications.
References:
1.
Alberti K, Zimmett P, De Fronzo
R.
International Textbook of diabetes mellitus
2nd ed. Chichester : John Wiley & Sons, 1997.
2.
Stampler J, Vaccaro O, Neaton JD
et al
For the
MRFIT Reseach Group Diabetes, Other risk factors and 12 year cardiovascular
mortality for men screened in the multiple risk factor intervention trial
Diabetes Care 1993; 16:424-44
3.
Kannel WB, McGee DL.
Diabetes and cardiovascular disease : the Framinghan Study.
JAMA 1979;241 : 2035-8.
4.
United Kingdom Prespective
Diabetes Study Group
Lancet. 1998; 352:837-853.
5.
Ramachandran A.
Diabetes Research Centre, Chennai
Personal Communication.
6.
Chawla R, Rathor P- North Delhi
Diabetes Centre –
To
study the prevalence of Diabetic peripheral Neuropathy by biothesiometric
evaluation & its co-association with other complications – Novonordisk
Diabtes update – 2004 proceedings.
7.
Morgan CL et al.
Diabet Med. 2000; 17:146-151
8.
Lawrence J, Robinson A.
Prev.
Cardiol 2003;6:78-84
9.
Stratton IM, Adler AI
Association
of glycemia with macrovascular and microvascular complications of Type-2
diabetes (UKPDS35) : Prospective observational study.
BMJ 321
: 405 – 412, 200.
10.
Chawla R, Arora G, Ahuja CP.
To
evaluate the clinical profile and determine the prevalence of complications in
newly diagnosed Type-2 Diabetic patients.
RSSDI-2005
11.
Garg JP, Bakris GL :
Microalbuminuria
: Marker of vascular dysfunction, risk factors for cardiovascular disease.
Vasc. Med 7:35-43, 2002
12.
Gall MA, Hougaard P, Borch
Johnsen K, Parving HH
Risk
factors for development of incipient and overt diabetic nephropathy in patient
with non insulin dependent diabetes : prospective observational study.
BMJ 314
: 783-788, 1997
13.
American Diabetes Association :
Nephropathy in diabetes (position statement)
Diabetes Care 27 (Suppl –1) : S79-S83, 2004
14.
Fong DS, Aiello LP, Ferris FL 3rd
, Klein R: Diabetic Retinopathy : Diabetes Care 27: 2540-2553, 2004.
15.
Vijan S, Hofer TP, Hayward RA
Cost
utility analysis of screening intervals for diabetec retionopathy in patients
with T-2 DM.
JAMA
283 : 889-896, 2000
16.
The Diabetes Control and
complications Trial Research group : effect of pregnancy on microvascular
complications in the diabetes control & complication trial.
Diabetes Care 23: 1084-1091, 2000
17.
Boulton AJ, Vinik AI, Arezzo Jc –
Diabetic Neuropathy
a statement by American Diabetes Association
Diabetes Care – 28: 956-962, 2005
18.
Vinik AI, Mehrabyan A :
Diabetic neuropathies
Med clin North Am 88:947-999, 2004
19.
Vinik AI, Maser RE, Mitchell BD
Diabetic Autonomic Neuropathy
Diabetes Care 26:1553-1579, 2003
20.
American Diabetes Association
preventive foot care in diabetes (Position statement) –
Diabetes care (suppl 1) S63-S64, 2004.
21.
American Diabetes Association
Peripheral arterial disease in people with diabetes (consensus
statement)
Diabetes care 26:3333-3341, 2003.
22.
American Diabetes Association
Consensus
development conference on Diabetic foot wound care : 7-8 April 1999, Boston,
Massachusetts, American Diabetes Association.
Diabetes Care 22 : 1354-1360, 1999.
23.
Stamler J. , Vaccaro O, Neaton JD
:
Diabetes,
other risk factors and 12 yr. cardiovascular mortality for men screened in
MRFIT.
Diabetes
Care 16:424-444, 1993
24.
Alder AI, Stratton IM, Neil HA –
Association
of systolic blood pressure with macrovascular & microvascular complications
of T-2 Diabetes (UKPDS 26) – Prospective observational study.
BMJ 321: 412-419, 2000.
25.
Pyorala K, Pederson TR, Kjekshus
J.
Cholesterol
lowering with simvastatin improves prognosis of diabetic patients with Coronary
heart disease – a subgroup analysis of the Scandinavian Simvastatin Survival
Study (4S)
Diabetes
Care 2-:614-620, 1997
26.
American Diabetes Association
Consensus
development Conference on the diagnosis of CAD in people with diabetes – 10-11
Feb, Miami, 1998, Florida.
Diabetes
Care 21:1551-1559, 1998.
27.
Wackers FJ, Young LH, Inzucchi
SE,
Detection
of Ischaemia in asymptomatic Diabetics subjects : the DIAD Study
Diabetes
Care 27: 1954-1961, 2004.
28.
Valensi P, Sachs RN, Harfouche B.
Predictive
value of cardiac autonomic neuropathy in diabetic patients with or without
silent myocardial Ischaemia
Diabetes Care 24:339-343, 2001
29.
Saydah SH, Fradkin J, Cowie cc
Poor
control of risk factors for vascular disease among adults with previously
diagnosed diabetes
JAMA
291, 335-342, 2004.
30.
The Diabetes Control &
complications Trial Research Group
The
effect of intensive treatment of diabetes on the development and progression of
long term complications in Insulin dependent diabetes mellitus.
N Engl
J Med 329:977-986, 1993
31.
UK prospective Diabetes study
(UKPDS) Group
Intensive
blood glucose control with SUs or Insulin compared with conventional treatment
and risk of complications in patients with type –2 diabetes (UKPDS 33)
Lancet
352 : 837-853, 1998
32.
UKPDS study design, progress and
performance-
UKPDS VIII, Diabetologia 34 : 877-90, 1991
33.
Mckinlay J, Marceau L-U.S. Public
health and 21st century : Diabetes Mellitus
Lancet, 356 : 757-61, 2000