Comparison of retinopathy in insulin-dependent diabetics with and without thyroid disease.
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Biomedical subjects
Publications and source records attributed to B F Clarke.
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All newly diagnosed insulin dependent diabetics presenting consecutively to the Diabetic Department of the Royal Infirmary from the City of Edinburgh or its environs, between the years 1964 and 1977, were analysed for sex (297 males, 205 females), age at diagnosis (range 10--75 years), month of diagnosis, duration of symptoms and month of symptomatic onset. Males aged 10--19 years showed a significant seasonal variation in diagnosis (p less than 0.025) with an increase in autumn and winter months which was not seen in females aged 10--19 years nor in patients of either sex aged more than 19 years at diagnosis. The duration of diabetic symptoms increased with increasing age at diagnosis in both males and females and was consistently greater in females than in males for each age group at diagnosis. When the month of symptomatic onset was considered in relation to sex and age at diagnosis, having excluded patients with duration of symptoms of more than three months, only males aged 10--19 years at diagnosis showed a significant seasonal variation in incidence (p less than 0.005).
This review attempts to outline the present understanding of diabetic autonomic neuropathy. The clinical features have been increasinly recognised but knowledge of the localization and morphology of the lesions and their pathogenesis remains fragmentary. A metabolic causation as postulated in somatic nerves accords best with clinical observations. Most bodily systems, particularly the cardiovascular, gastrointestinal and urogenital, are involved with added disturbances of thermoregulatory function and pupillary reflexes. Possible effects on neuroendocrine and peptidergic secretion and respiratory control await definition. Current interest centres around the development of a new generation of tests of autonomic nerve function that are simple, non-invasive, reproducible and allow precision in diagnosis and accurate quantitation. Most are based on cardiovascular reflexes and abnormality in them is assumed to reflect autonomic damage elsewhere. Probably no single test suffices and a battery of tests reflecting both parasympathetic and sympathetic function is preferable. Little is known of the natural history. The prevalence may be greater than previously suspected and although symptoms are mild in the majority, a few develop florid features. The relation of control and duration of diabetes to the onset and progression of autonomic neuropathy is not clearly established. Once tests of autonomic function become abnormal they usually remain abnormal. Symptomatic autonomic neuropathy carries a greatly increased mortality rate possibly due to indirect mechanisms such as renal failure and direct mechanisms such as cardio-resiratory arrest. Improved treatment of some of the more disabling symptoms has been possible in recent years.
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The left ventricular response to the Valsalva manoeuvre was studied in 5 normal subjects (group 1), 6 diabetics without autonomic neuropathy (group 2), and 5 diabetics with autonomic neuropathy (group 3), using the maximum amplitude of the praecordial accelerocardiogram (DE) as a noninvasive index of left ventricular performance. During the Valsalva manoeuvre DE decreased in all 3 groups. In groups 1 and 2, DE increased significantly above the control value after release of the manoveuvre (DE overshoot) but this did not occur in group 3. It is suggested that the overshoot of DE in groups 1 and 2 reflects an increase in left ventricular contractility after release of the Valsalva manoeuvre and the absence of an overshoot in DE in the patients with autonomic neuropathy is the result of loss of cardiac adrenergic innervation. The ability to detect an abnormal cardiovascular response to the Valsalva manoeuvre using the non-invasive technique of praecordial accelerocardiography may be of practical value in the assessment of left ventricular function.
Fifty-one diabetic patients with mononeuropathies wereoneuropathy were studied to examine possible etiological factors, to determine the relationship with other diabetic complications, and to correlate with the presence and severity of background peripheral and autonomic neuropathy. The median, ulnar, and lateral popliteal nerves were most commonly affected and cranial neuropathy was relatively uncommon. When bilateral involvement of the same nerve was excluded, multiple mononeuropathies were found in only five patients. Median and ulnar mononeuropathy were gradual in onset and affected the dominant limb whereas other types of mononeuropathies were acute in onset with no predilection for either side. No consistent relationship was shown between the onset of mononeuropathy and age, sex, diabetic treatment, duration of diabetes, diabetic control, or other diabetic complications. In particular, there was no significant background peripheral and autonomic neuropathy, as assessed clinically and by objective tests, in almost one-half of the patients studied. It is concluded that diabetic mononeuropathy may occur independently of peripheral and autonomic neuropathy. It is possible, however, that a minimal degree of background damage, known to be present in all diabetic patients, may render them more susceptible than the general population to the various factors causing mononeuropathy.
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The immediate heart-rate response to standing was measured in 22 normal controls and 25 patients with diabetes, 15 of whom had autonomic neuropathy. The response in the controls and patients without autonomic neuropathy was characteristic and consistent, with tachycardia maximal at around the 15th beat and relative bradycardia maximal at around the 30th beat. The diabetics with autonomic neuropathy, however, showed a flat response. In three controls the response was abolished with intravenous atropine but not with propranolol, showing that it is mediated through the vagus. A simplified test using routine ECGs and measuring the R-R interval at beats 15 and 30 with a ruler is easily performed as an outpatient procedure and may be used as a measure of autonomic function in diabetes.
The clinical effectiveness of metformin was compared with that of chlorpropamide in closely similar groups of 216 non-obese patients recently diagnosed as cases of maturity-onset diabetes that could not be controlled by diet. The incidences of primary and secondary drug failures in each group and the numbers of patients satisfactorily maintained on each of the hypoglycaemic agents throughout the first year proved remarkably similar. In 61 of the successfully treated patients who were studied by crossover to the other drug and observed for a further year the mean blood glucose concentrations at the end of the year were roughly comparable, but the mean weight response was a small loss of 1.5 +/- 3.8 kg with metformin but a gain of 4.6 +/- 3.9 kg with chlorpropamide. Thus for non-obese, maturity-onset diabetics whose disease cannot be controlled by diet and who require oral treatment sulphonylureas and biguanides are equally effective, the choice depending on whether the patient is underweight and the severity of symptoms.
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A study of 296 diabetics demonstrated an association between the type of diabetes in the propositi and their first-degree relatives (aged 40 to 89 yr), the type of diabetes being defined as insulin-dependent (type I) or insulin-independent (type II). This association was significant at the 1% level and was still maintained when only the propositi in whom the diabetes was diagnosed at the age of 30 years or later were considered. The findings also suggest that there is a greater genetic independence between these two types than was previously supposed and that the disease should be subdivided into type according to the treatment needed rather than by the age of onset.
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Gastric emptying was studied in 12 diabetic patients, six with and six without objective evidence of autonomic neuropathy and in 20 non-diabetic controls, using a double isotope scinti-scanning technique which differentiated between solid and liquid emptying. Three patients with autonomic neuropathy exhibited gastric stasis, although this was detected by conventional radiology in only one. Neither the patients with stasis nor those without exhibited abnormally rapid early gastric emptying. In patients without stasis, the normal differentiation between solid and liquid emptying was impaired, suggesting an abnormality of antral peristalsis not attributable to vagal denervation. Both intravenous and oral metoclopramide produced symptomatic improvement in two patients with gastric stasis and restored their gastric emptying to normal.
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The plasma beta-thromboglobulin (betaTG) content was measured in 56 diabetic patients with known complications of this disease, including neuropathy, retinopathy, and ischemic skin lesions. Although two patients were found to have elevated levels beyond the normal range, there was no significant difference between the diabetic group as a whole and the group of 35 controls. The significance of these findings with regard to the proposed contribution of small-vessel platelet sequestration in the pathogenesis of late complications of diabetes mellitus is discussed.