Clinics in Endocrinology and Metabolism最新文献

Diabetic retinopathy is a common, and potentially blinding or visually disabling complication of diabetes. Nearly all diabetic subjects will have some degree of retinopathy after 20 years of diabetes, and 50% of those with insulin dependent diabetes will have proliferative retinopathy after 15 years. Macular oedema frequently produces central vision loss and legal blindness, most commonly in non-insulin dependent diabetics.

In recent years, several therapeutic modalities have been demonstrated to be effective on the basis of large-scale randomized, controlled clinical trials. These include panretinal photocoagulation (PRP), using the argon laser or xenon arc, for proliferative retinopathy, and focal photocoagulation for macular oedema. Vitrectomy surgery is effective for diabetic vitreous haemorrhage and traction retinal detachment, producing improved vision in most patients, but only a relatively small percentage of patients so treated recover good visual acuity (⩾ 6/12). Other therapeutic modalities, such as hypophysectomy for severe retinopathy, remain controversial, while still others, such as rigorous blood glucose control and aldose reductase inhibitors, are currently under investigation.

The primary care physician who deals with diabetic patients should be familiar with the lesions of diabetic retinopathy and with current therapeutic modalities. He should perform an examination of the posterior retina with the direct ophthalmoscope on each diabetic patient at each visit, and should institute prompt referral to an ophthalmologist at the first sign of change. Periodic examination of all diabetic patients by an ophthalmologist should be conducted at the intervals recommended in the previous section. Definitive evaluation and treatment of diabetic retinopathy should be carried out by the ophthalmologist.

Diabetes causes cataract and certain physical changes in the lens. The diabetic lens is larger than the non-diabetic and shows greater light scatter and fluorescence. Both hyperglycaemia and lowering of blood glucose cause refractive changes and hypermetropia is the most common. Classical ‘snow-flake’ juvenile cataract associated with hyperglycaemia is now rare. It has an osmotic mechanism. Diabetes is a risk factor for cataract in adults which is duration dependent, more frequent in women and leads to earlier surgery. It resembles non-diabetic senile cataract. Extracapsular cataract extraction is the method of choice for diabetic cataract with a better visual result and less risk of rubeosis iridis. A posterior chamber implant may still permit retinal photocoagulation if necessary.

Diabetic retinopathy is still the leading cause of blindness in the working age group. The beneficial effect of photocoagulation has been shown by randomized controlled trials to be long-lasting for both proliferative retinopathy and maculopathy. Therefore there is a need for screening, especially for those with proliferative disease which may be present without symptoms. A knowledge of risk factors will enhance detection rate with duration as the strongest determinant for retinopathy.

Any screening modality should be highly sensitive as well as specific. The role of different professionals as potential screeners should be considered.

Adequate provisions include facilities for checking vision and for dimming ambient lighting. Mydriasis and a good ophthalmoscope light will increase detection rate.

The use of a 45° non-mydriatic camera is unlikely to supplant the use of an ophthalmoscope as a single field is likely to miss important lesions.

A 60° camera may confer a large enough field and the use of transparencies will provide magnification when films are projected but the camera is more difficult to use.

A list of features chosen by a recent study to characterize sight-threatening retinopathy is included and their presence indicates the need for referral to an ophthalmic clinic for treatment or close observation.

Autonomic neuropathy is now well established as a relatively common and significant complication of diabetes mellitus. Its importance has been clarified in recent years during which the extent of autonomic control over all areas of body function has been defined. Using simple cardiovascular reflex tests, autonomic abnormalities can be demonstrated without any corresponding symptoms. The often stated concept of ‘patchy’ involvement in diabetic autonomic neuropathy should now be rejected as too should the view that autonomic neuropathy is either ‘present’ or ‘absent’ based on a single test result. When generalized and predominantly metabolic disturbances, as in diabetes, give rise to impaired nerve function, autonomic as well as somatic components of the nerve are affected. Where damage is severe this leads to the characteristic florid picture of symptomatic autonomic neuropathy with its particularly poor prognosis.

For the physician in a busy clinic, much of the theoretical and experimental basis for autonomic neuropathy may not appear of direct relevance. However, he has now to be aware of the clinical implications of autonomic damage in the diabetic. This may have particular relevance in the care of the diabetic foot (see Chapter 10), the recognition of many of the vague symptoms associated with autonomic damage, the treatment of disabling features such as postural dizziness and nocturnal diarrhoea, and an awareness of the poor prognosis associated with symptomatic autonomic neuropathy. He will also need to be alert to the dangers of general anaesthesia in such patients, and the possibility of sudden unexpected deaths.

Diabetic autonomic neuropathy causes widespread abnormalities, some of which are clinically apparent, some of which can be detected by sensitive tests, and others which have yet to be discovered. Inclusion of the neuropeptides and other hormones within the compass of autonomic control has opened up a whole new area of investigative interest, with many complex interrelationships which still need to be unravelled. This should lead to better understanding of the pathophysiological processes that cause damage to diabetic nerves. With so much research effort directed towards better glycaemic control and aldose reductase inhibitors (see Chapter 8), it may eventually be possible to reverse or prevent this potentially disabling and lethal complication of diabetes.

Duration of disease is the major susceptibility factor for microangiopathy. Microangiopathy does not occur without the metabolic abnormality of diabetes and there is much circumstantial evidence to implicate poor diabetic control in its pathogenesis. The rate of development and severity of complications, however, are variable even in patients with apparently similar control and about 25% of diabetics will never develop clinical evidence of microangiopathy. Studies of identical twins suggest a genetic component in the pathogenesis of retinopathy in NIDDM, and less so in IDDM, but increased capillary basement membrane thickness does not occur in the non-diabetic identical co-twins of insulin dependent diabetics. There may also be genetic heterogeneity not only of diabetes, but also of its complications, although for a given type of diabetes the prevalence of microangiopathy is often very similar in different racial groups.

]Associations between several different HLA molecules (particularly DR4) and microangiopathy in IDDM have been reported but not consistently confirmed. Recently the finding of an increased frequency of the B3 allotype of the fourth component of complement C4B3 in subjects with retinopathy has suggested that there is an HLA linked association. Both complement and the immunoglobulins are concerned with humoral immunity and the report of an association between a phenotype of the IgG heavy chain markers on chromosome 14 and retinopathy is of particular interest. These associations appear to be additive but independent. These reports need confirmation but provide the best evidence we have for an immunogenetic component (HLA and non-HLA linked) of the aetiology of microangiopathy, at least in IDDM.

]The studies of identical twins, HLA and Gm associations provide good evidence that genetic factors are involved in susceptibility to microangiopathy, at least in some diabetics, although the most relevant genes may not have been identified. Searches for better genetic markers must continue in order to identify those patients at increased risk of developing microangiopathy.

• 1.

  Diabetic nephropathy develops in about 45% of insulin dependent diabetics of whom two-thirds will develop renal failure, the rest dying from cardiovascular disease.

• 2.

  Most of the excess mortality of insulin dependent diabetics occurs in those with proteinuria.

• 3.

  Among non-insulin dependent diabetics nephropathy is also an important cause of increased mortality but this is mainly from cardiovascular disease.

• 4.

  Once diabetic nephropathy is established it progresses relentlessly to end-stage renal failure over about seven years, but ranging from five to 20 years. The explanation for the different rates of progression in individual patients is not understood.

• 5.

  Hypertension accompanies diabetic nephropathy and its treatment may retard the progression of renal failure.

• 6.

  Other forms of intervention include glycaemic control which has not been shown to have any effect, and protein restriction for which no conclusions can be drawn at present.

• 7.

  The diagnosis of diabetic nephropathy is straightforward in the presence of a typical history and clinical features. Non-diabetic renal disease is sometimes the cause of renal failure and may require specific treatment; prognosis for renal failure treatment may be better than for nephropathy patients with other diabetic complications.

• 8.

  Other diabetic complications develop as diabetic nephropathy progresses, most notably cardiac and peripheral vascular disease. Proliferative retinopathy and neuropathy are considerable problems and their management needs attention both before and after renal failure treatment.