“Vascular  Complications in Diabetes – Its clinical evaluation & screening”

 

DR. RAJEEV CHAWLA

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.

 

Screening for Macrovascular Complications

 

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