The chronic complications of diabetes involve the small (microvascular) and large(macrovascular) vessels of the body.
Macrovascullar Complications
Diabetics are Inore vulnernhle to all~erosclerosis than non-diabetics. The large vessels supplying the heart, brain iuid periplicries are the areas where atherosclerotic vessels cause life-threatening clinical events. There are risk factors li)r atherosclerosis other than diabetes, namely smol<ing, hypertension, liypcrlipidemia, lnale sex, :und central obesity and genelic I'rictors. Hence macro-vascular complications :Ire more lil<ely to occur in those who have these i~dditional risk f'actors. This has iniportant implicntions
in the management and cont1.01.Good control ol'diilbetcs is essential in improving tlic prognosis of patients who have developecl these complications. tloweve~; since the pathogcncsis of macro-vascular disease is multi-factorial, perfect control 01' ciiribctcs per se is not known to prevent (both primary and secondary prevention) tlicsc complications.
Diabetics have charnctcristic lipid :~l?norniulitics. 'Uney tend to have clcvutcd triglyceride levels, rind low high dctisity lipopl-otcins (HDI,). Tlnougli clevatecl t~iglycerides are not known lo he parliculrlrly atherogcnic in non-diabetics, they huvebeen shown to pose u high nthcrogcnic risli in diabetics.Low HDL lcvcls are known to be athcrogcnic in non-diabetics ancl the salnc holcis true in the clii,helic population.Low clensily lipoprotein: licccnlly there Inns been rcsenrch interest in thc conil,osilion of low density lipoprotein fraction (L,DI,) in dinbctics. Thc m:ljor LDL 1'r:lction in normal serum contains npo-R. In diahctics, a greater proportion of LUI, also contai~ls apo(a), and are rich in triglycericics, This [,Dl., is also known us Lp(a), the particles are small and dense, ancl are tlioi~gltl to be more athcrogcnic.
Good control of diabetes lowers TG and LIIL levels but I-IDL levels tend lo remain low, though insulin 1Iicr;lpy and cxercisc is shown to elevate I-IDL.High levcls of bloocl sugar over a long period of time result in "glycosylntion" ~und "oxidation" of the lipopt-oteins; this is important in pathogenesis of v:lscula~.complicntions, and arc menlionetl in clctnil Intel..
Hypertension is rnore prevalent in the diiil3clic population versus the non-diabetics.The pathogenesis of Iiyl,cr~ension is related to the following:
a) Rertal clisense: The onset of ncpliropatlny accelerates prc-cxisting hypertension in diabetics, and usually initiates hyj~ertension in those who were previously nonnotensive.
b) Hypertension: Hypertension is present in dinbctics (without renal diseasc) with the twice the frequency in non-diabelics. 7his excess prevalence of liypel-tension is thought to be related to hyperinsulinert~ia, ~mtl obesity. The mechanisms by which hypcrinsulinemia causcs hypertension has been studied and is possibly mediated via increased sodiurn retntion by the kidney tubules, ancl by increasing vascular tone and thereby peripheral sesisitnoce.
C)Ortlzostntic hypotension: This is occur in diabetics who have autonomic neuropathy, or severe cardiomyopathy which results in a decreased cardiac output.
d) Isolated systolic hypertension: This is defined as a systolic pressure at o r above 160 mm Hg with diastolic pressure less than 90 min Hg. This is a result of atherosclerotic rigidity or decreased elasticity of arteries. Normally the larger anel-ies expand during systole to accoinlnodate the larger volume; when this cannot occur, there is a sudden elevation in pressure during systole.
Obesity: Obesity and type 11 diabetes are closely related, both conditions manifesting insuliil resistance.
Coronary Artery Disease
Diabetics are very prone to developing coronary artery disease which occurs at younger ages than in the non-diabetic population. Non-diabetic pren~enopausal women ate protected from ischemic hear1 disease, but this advantage is lost in diabetic women, in whoin the prevalence of heart disease equals that in men. Hence a young diabetic woman complaining of chest pain must be considered to have ischemic heart disease unless proved otherwise.The National Diabetes Education Piogramine, USA states that 65 per cent of deaths in diabeteics are due to cardiovascular disease.
Macrovascullar Complications
Diabetics are Inore vulnernhle to all~erosclerosis than non-diabetics. The large vessels supplying the heart, brain iuid periplicries are the areas where atherosclerotic vessels cause life-threatening clinical events. There are risk factors li)r atherosclerosis other than diabetes, namely smol<ing, hypertension, liypcrlipidemia, lnale sex, :und central obesity and genelic I'rictors. Hence macro-vascular complications :Ire more lil<ely to occur in those who have these i~dditional risk f'actors. This has iniportant implicntions
in the management and cont1.01.Good control ol'diilbetcs is essential in improving tlic prognosis of patients who have developecl these complications. tloweve~; since the pathogcncsis of macro-vascular disease is multi-factorial, perfect control 01' ciiribctcs per se is not known to prevent (both primary and secondary prevention) tlicsc complications.
Diabetics have charnctcristic lipid :~l?norniulitics. 'Uney tend to have clcvutcd triglyceride levels, rind low high dctisity lipopl-otcins (HDI,). Tlnougli clevatecl t~iglycerides are not known lo he parliculrlrly atherogcnic in non-diabetics, they huvebeen shown to pose u high nthcrogcnic risli in diabetics.Low HDL lcvcls are known to be athcrogcnic in non-diabetics ancl the salnc holcis true in the clii,helic population.Low clensily lipoprotein: licccnlly there Inns been rcsenrch interest in thc conil,osilion of low density lipoprotein fraction (L,DI,) in dinbctics. Thc m:ljor LDL 1'r:lction in normal serum contains npo-R. In diahctics, a greater proportion of LUI, also contai~ls apo(a), and are rich in triglycericics, This [,Dl., is also known us Lp(a), the particles are small and dense, ancl are tlioi~gltl to be more athcrogcnic.
Good control of diabetes lowers TG and LIIL levels but I-IDL levels tend lo remain low, though insulin 1Iicr;lpy and cxercisc is shown to elevate I-IDL.High levcls of bloocl sugar over a long period of time result in "glycosylntion" ~und "oxidation" of the lipopt-oteins; this is important in pathogenesis of v:lscula~.complicntions, and arc menlionetl in clctnil Intel..
Hypertension is rnore prevalent in the diiil3clic population versus the non-diabetics.The pathogenesis of Iiyl,cr~ension is related to the following:
a) Rertal clisense: The onset of ncpliropatlny accelerates prc-cxisting hypertension in diabetics, and usually initiates hyj~ertension in those who were previously nonnotensive.
b) Hypertension: Hypertension is present in dinbctics (without renal diseasc) with the twice the frequency in non-diabelics. 7his excess prevalence of liypel-tension is thought to be related to hyperinsulinert~ia, ~mtl obesity. The mechanisms by which hypcrinsulinemia causcs hypertension has been studied and is possibly mediated via increased sodiurn retntion by the kidney tubules, ancl by increasing vascular tone and thereby peripheral sesisitnoce.
C)Ortlzostntic hypotension: This is occur in diabetics who have autonomic neuropathy, or severe cardiomyopathy which results in a decreased cardiac output.
d) Isolated systolic hypertension: This is defined as a systolic pressure at o r above 160 mm Hg with diastolic pressure less than 90 min Hg. This is a result of atherosclerotic rigidity or decreased elasticity of arteries. Normally the larger anel-ies expand during systole to accoinlnodate the larger volume; when this cannot occur, there is a sudden elevation in pressure during systole.
Obesity: Obesity and type 11 diabetes are closely related, both conditions manifesting insuliil resistance.
Coronary Artery Disease
Diabetics are very prone to developing coronary artery disease which occurs at younger ages than in the non-diabetic population. Non-diabetic pren~enopausal women ate protected from ischemic hear1 disease, but this advantage is lost in diabetic women, in whoin the prevalence of heart disease equals that in men. Hence a young diabetic woman complaining of chest pain must be considered to have ischemic heart disease unless proved otherwise.The National Diabetes Education Piogramine, USA states that 65 per cent of deaths in diabeteics are due to cardiovascular disease.
Pel-ipheral Vascular Disease (BVD)
Occlusion of the lower Liinb arteries is a known complication and is responsible along with neuropathy for foot ulceration and amputations in diabetics. The occlusion may be at the a0110 iliac site, superficial femoral; or the tibia1 arteries. The small vessels of the foot themselves are rarely involved. Clinical examination of a diabetic includes feeling all distal pulses, as well feeling the femoral and popliteal pulsations.
PVD is seen in the following sites:
1) Aorto-iliac: This leads to pain in the buttocks and thighs.
2 ) Femoro-popliteal: This leads to typical calf-claudication.
3)Leriche syndrome: This is due to distal aortic occlusion leading to absence of both femoral pulses, claudication and impotence.In advanced PVD, the patient has pain at rest with some relief on hanging the feet down from the edge of the bed. The skin is mottled and cool, ulcerations and gangrene may be noted.
AnMeBrachial Index: Using a small portable Doppler instrument blood pressures at the ankle and brachial arteries are checked. The ankle brachial systolic pressure ratio is usually more than one, but in PVD it is <I, and in severe disease may be ~ 0 . 5 .
Occlusion of the lower Liinb arteries is a known complication and is responsible along with neuropathy for foot ulceration and amputations in diabetics. The occlusion may be at the a0110 iliac site, superficial femoral; or the tibia1 arteries. The small vessels of the foot themselves are rarely involved. Clinical examination of a diabetic includes feeling all distal pulses, as well feeling the femoral and popliteal pulsations.
PVD is seen in the following sites:
1) Aorto-iliac: This leads to pain in the buttocks and thighs.
2 ) Femoro-popliteal: This leads to typical calf-claudication.
3)Leriche syndrome: This is due to distal aortic occlusion leading to absence of both femoral pulses, claudication and impotence.In advanced PVD, the patient has pain at rest with some relief on hanging the feet down from the edge of the bed. The skin is mottled and cool, ulcerations and gangrene may be noted.
AnMeBrachial Index: Using a small portable Doppler instrument blood pressures at the ankle and brachial arteries are checked. The ankle brachial systolic pressure ratio is usually more than one, but in PVD it is <I, and in severe disease may be ~ 0 . 5 .
Diabetic Foot
As stated earlier foot ulceration and gangrene occurs due to a combination of ischemia and neuropathy. The features of a neuropathic foot and of a neuro-ischemic foot are given in the box below:
As stated earlier foot ulceration and gangrene occurs due to a combination of ischemia and neuropathy. The features of a neuropathic foot and of a neuro-ischemic foot are given in the box below:
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| The Ncuropnthic Ulccr |
Pathogenesis o i Foot Ulceration
In the neuropathic foot small intrinsic muscles of the foot atrophy causing 'hammer-toe deformity", or curling-up of the toes. There is excessive pressure on the metatarsal heads. Thickening of the plantar surface of the foot just beneath the metatarsal heads takes place. These corns and calluses are liable to fissuring,Cardiovnscular Related Disorders allowing infection to enter and cause ulceration. Situations that prolnote ently of infection into the foot are:
1) Breaks in the skin from fissures, corns and calluses.
2) Maceration of' skill between toes due to inadeclunte dryi~ig, or perspiration.
3) Fungal infections, and other dermatitis.
4) Heat, intense cold, or chemical issitants can cause blistering and subsecluently infection.
5) Ill-fitting shoes cause blistering.
6) Toe nail injury at the time of cutting, or by an ingrowing toe nail.
7)Odema of the foot leads to infection.
Once infection gains entry, it can spread rapidly because of the repeated friction from.weight-bearing, ischemia and tlie poor healing due to the laetabolic dcfect. Hence the following foot-care lips should be taught to all diabetics and stressed repeatedly at each visit:
Foot-care Tips
1) Never walk barefoot both inside and outside the house.
2 ) Wash and dry feet daily and inspect it for fissures, blisters, ulcerations, and report to the doctor immediately.
3)Cut toenails "across" in a straight line, and not curve at the edges.
4) Do not apply heat in any f o m ~ to the feet.
5 ) Chappals should be well fitting. The ideal chappal for a pa~ient with neuropathy is one which has a sole nlade of micro-cellulm rubbec There should be a back-strap so that the chappal can be held in contact with foot without the need Lo gi-ip with the toes (which are weak and will cause the cahppal to slip off]. There should be no toe hold as this may constrict the big toe, and is difficult to put on.
Management of Neuropathic Ulceration
Reinoval of Callus
The callus should be pared off with a scalpel very cuefi~lly to expose the floor of the ulcer and allow drainage and healing. This is best done by a foot specialist (podiatrist, but such specialists are not available in India. A dermatologist ma) be approached).
Infection Eradication
This is a polyinicrobial infection, hence broad spectru~n antibiotics are needed. A small superficial ulceration can be treated as an outpatient with strict bed rest and antibiotics such as quinolones, oral cephalosporins. Daily dressings are mandatory,and a physician should inspect the foot every 2-3 days. If there is cellulitis, gangrene then urgent hospitalization is mandatory. In this situation intravenous antibiotics such as 3rd generation cepahalosporinsfor augmentin and metronidazole should be administered intravenously (check guidelines). Surgical debridement needs to be doneto remove necrotic tissue, drainage of pus collections, and amputation of gangrenous digits (ray amputation).
Amputation
Often infection cannot be contained by these measures and below knee or above knee amputations become necessiu-y. Limited amputations such as trans metatarsal amputation of the forefoot is also done to preserve Home function.
Medical Management
Aspirin is useful in long-term secondary prevention. Pentoxyphylline (trental) appears to be of some benefit. Recently a new drug cilostazol has been foi~nd to be better in improving sy~nptoms in affected patients.
Revascularization
Surgical bypass grafting is the gold standard and has a high patency rate a1 five years,with the besl results in aorto-iliac disease. The vessels below the tibia were coilsidered to be inaccessible for bypass duc to their snlall size, but infra-popliteal bypasses are being done successfully. Such procedures can cause rapid her-lling of recalcitranl 11011-healing foot ulcers. Unforluniltely few centers in India have the expertise for vascular surgery.
Percuta~eous artery dilatation an? stent insertions have now becoine available, but their patency rate is not yet as long-lasting as surgical therapy. However, Lhis is an attractive though expensive alternative to surgery.
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