Postgrad Med J: first published as 10.1136/pgmj.23.258.185 on 1 April 1947. Downloaded from

THE DIAGNOSIS AND TREATMENT OF GLYCOSURIA By STELLA INSTONE, M.D., M.R.C.P. Assistant Physician, New Sussex Hospital for Women, Brighton

Part I. The Diagnosis of Glycosuria I. Diabetic Glycosuria When a young adult complains of thirst, Introduction excessive hunger, polyuria, exhaustion and Since glycosuria is often found only on loss of weight, the discovery of glycosuria routine examination of the urine, the impor- usually confirms an obvious diagnosis of tance of this simple procedure in every case is Diabetes Mellitus. Milder cases, especially in obvious. Unless this symptom is severe or patients over middle age, may have less marked long-standing, many of these patients make no symptoms. Minor degrees of wasting and suggestive complaint when first seen. lassitude should not be dismissed without When .a reducing substance is found in the examination of the urine, together with a glucose tolerance test, or at least a urine, it is necessary to prove that it is glucose. fasting by copyright. Fehling's solution should not be used, since blood-sugar estimation, if glycosuria is found. this reagent is reduced not only by sugar, but Sometimes one of the complications of also by uric acid, glycuronic acid and diabetes may first suggest the need to test the creatinine; the degree of reduction is slight, urine. Thus the patient may present with usually only a change in colour to green or recurrent boils, carbuncles or other septic vellowish-green. The more delicate Benedict's infection. It is important in such cases not to test may detect such sugars as lactose, laevulose miss a diabetic origin, so that the patient may be or pentose, which need more elaborate tests for properly prepared for any operative treat- http://pmj.bmj.com/ their identification. ment needed. Lactosuria is suggested by the presence of Pulmonary tuberculosis *is common in sugar in the urine during pregnancy or lacta- diabetics, and its symptoms may be few and tion, or when breast-feeding is suddenly undetected unless the chest be X-rayed in stopped. Lactose is identified by the yeast- every case. Less often, the pulmonary lesion fermentation test (glucose being the only sugar may cause symptoms before diabetes is which ferments yeast), and by the characteristic suspected; in these cases a urine test is most on September 29, 2021 by guest. Protected 'hedgehog' crystals of lactosazone. Laevulo- important. suria may occur during the course of liver Nervous symptoms may have a diabetic disease. Pentosuria is extremely rare. basis. In addition to peripheral neuritis, pains The usual type of glycosuria is due to the in the legs resembling sciatica may be associated presence ofglucose in the urine. Four varieties with diabetes, without other suggestive will be considered. symptoms. I. Diabetic Glycosuria. In severe diabetes the tendon reflexes may II. Renal Glycosuria. be absent, and paraesthesia and signs of posterior column involvement may lead to a III. Glycosuria of Cerebral Origin. suspicion of tabes unless their origin is IV. Glycosuria of Endocrine (non- appreciated. In cases of failing vision, the pancreatic) origin. urine should always be tested; diabetic Postgrad Med J: first published as 10.1136/pgmj.23.258.185 on 1 April 1947. Downloaded from i86 POST-GRADUATE MEDICAL JOURNAL APril, I 947 cataract and retinitis can be improved, or at Alimentary Glycosuria least 'arrested in their progress, by early In this condition, after a large meal of treatment. carbohydrate, the patient passes sugar in the urine. There may be no diabetic symptoms, Coma and renal glycosuria may be suspected, but a In every unconscious patient, whatever the glucose tolerance test will show that the blood history, the urine must be examined for sugar, sugar rises abnormally high and takes unduly acetone bodies and albumen. The finding of long to return to its fasting value, which may glycosuria and ketosis strongly suggests be above the normal. These cases are diabetic coma,' but some cerebral lesions may essentially mild diabetics, with lowered carbo- produce these signs (q.v.). If there is a history hydrate tolerance, in which the insulin of previous diabetes the diagnosis is simple. produced is enough to deal with average, but Useful confirmatory signs are' the low ocular not heavy, carbohydrate meals. The transient tension (rarely found except in conditjons of glycosuria sometimes found in fat, hypertensive dehydration leading to coma), dry skin, lips women after middle age, is probably of this and tongue, a smell of acetone in the breath nature. and, if available, laboratory findings showing hypeiglycaemia and a lowered alkali reserve. II. Renal Glycosuria If blood sugar estimations are not available, The normal renal threshold for sugar, is the distinction of hypoglycaemia from diabetic about i8o mgm. per cent. and above this leval coma may be difficult. In the former, the onset the storage mechanisms prevent a further rise is more sudden, the skin moist and sweating of blood sugar. In cases of renal glycosuria, and the ocular tension -normal. Sugar and the renal threshold is lower than normal, and acetone are usually absent from the urine, at these patients pass sugar in the urine when the by copyright. least, in the second specimen obtained. The blood sugar is only I40-I50 mgm. per cent., immediate response to the giving of sugar in' or less. The patient is usually a healthy young hypoglycaemia is also diagnostic. adult without diabetic symptoms. He may Glycosuria may be an incident in coma due complain of recurrent boils, or of local pruritus, to poisoning, uraemia or a cerebral vascular but the glycosuria is often found only on lesion; in such cases there will be charac- routine examination. A glucose tolerance test teristic physical signs. Even when glycosuria shows that' the fasting blood sugar is rather is found, every comatose patient should, be low and that the blood sugar never, rises above http://pmj.bmj.com/ thoroughly examined to make sure that no i8o mgm. per cent.-usually'not above I50 lesion other than diabetes is present. In mgm. per cent.-but that sugar appears in the particular, one should note the state of the urine each time its blood level exceeds I40-150 reflexes, cranial nerves and pupil reactions, mgm. per cent. This test is the only certain also, the presence of any needle marks or signs method of diagnosing renal glycosuria. of poisoning. The breath may smell of acetone and so lead to the detection of III. Glycosuria of Cerebral Origin on September 29, 2021 by guest. Protected glycosuria. Since Claude Bernard first described glyco- When the cause of coma is in doubt, lumbar suria following puncture of the floor of the puncture should be done to exclude the fourth ventricle, the condition has been noted presence of a subarachnoid haemorrhage. In in many basal cerebral lesions. When neuro- some cases of severe diabetic coma, the logical signs predominate the case, and presence of albumen and casts in the urine glycosuria is incidentally found, there is no may suggest uraemia and may cause neglect of difficulty in diagnosis. Some difficulty may the essential treatment with insulin and arise from lesions near the fourth ventricle in glucose. In every case of coma the urine which glycosuria precedes other signs. should be examined for albumen and sugar In some cases of cerebral haemorrhage, and, if possible, the blood urea should be glycosuria and even acetonuria may occur- estimated. the latter following starvation and vomiting. Apl I947 DIAGNOSIS AND TREATMENT OF GLYCOSURIA I87 Postgrad Med J: first published as 10.1136/pgmj.23.258.185 on 1 April 1947. Downloaded from Subarachnoid haemorrhage is suggested by adrenalin upon the blood sugar. Great the sudden onset of intense headache, coma emotional disturbances may possibly produce and signs of meningeal irritation, often with glycosuria by means of an outpouring of glycosuria. The cerebrospinal fluid, first adrenalin. Such an effect would be transient, bloodstained and later stained yellow, is under but it is possible that prolonged mental strain greatly increased pressure, and is diagnostic. might, by the same mechanism, cause diabetes. Internal capsular haemorrhage may track This would explain the common development into the ventricle; but in this coma the onset of diabetes in times of stress. Any disturbance is more rapid than in diabetic coma, and there of function of the ductless glands which are some localizing signs, e.g., hemiplegia and antagonize the pancreas may, if sustained, conjugate deviation of the eyes. cause true diabetes. Glycosuria occurring, for Tuberculous meningitis occurs especially in example, in hyperthyroidism, cannot therefore childhood, in which diabetes is uncommon. be dismissed as unimportant. Even through glycosuria may coexist, the presence of meningeal irritation, ocular pareses Summary of Differential Diagnosis of and raised intracranial pressure should Glycosuria establish the diagnosis. i. The importance of routine examination of the urine is stressed. IV. Endocrine Glycosuria 2. If sugar is found, it must first be identified Sometimes diabetes is part of a generalized as glucose. pancreatic insufficiency; these cases show 3. If glycosuria is accompanied by hunger, other signs such as chronic dyspepsia, steator- thirst, polyuria, loss of weight and lassitude, rhoea, raised blood and urinary diastase, and the diagnosis is diabetes mellitus. a positive Loewi's adrenalin test. The signs Recurrent 4. septic infections, cataract or by copyright. may be due to pancreatitis, neoplasm or retinitis, pulmonary tuberculosis or other syphilitic infection. well-known complications of diabetes, should Glycosuria is not uncommon in thyroid and always call for an examination of the urine. pituitary diseases; the thyroid, pituitary and 5. Inconstant glycosuria in a healthy young suprarenal hormones antagonize insulin, so adult is probably due to a low renal threshold that their hypersecretion may cause a state of for sugar. This should be confirmed by a lowered carbohydrate tolerance. In hyper- glucose tolerance test. thyroidism, glycosuria and some degree of 6. If glycosuria only follows a heavy carbo- hyperglycaemia are common. If clinical signs hydrate meal, and there are no diabetic http://pmj.bmj.com/ are not obvious, a glucose tolerance test will symptoms, the possibility of a low carbohydrate usually show a normal fasting level but high tolerance must be confirmed, and distinguished blood sugar readings after food. from renal glycosuria, by a glucose tolerance A more difficult problem is the early test. diagnosis of acromegaly, in which glycosuria 7. Signs of raised intracranial pressure, or may also occur. The blood sugar findings are localizing cerebral signs, or evidence of on September 29, 2021 by guest. Protected the same as in hyperthyroidism. Enlargement meningitis or subarachnoid haemorrhage in a of the nose, tongue, supraorbital ridges, hands case of glycosuria, should suggest that the and feet; pressure signs such as headaches latter is only incidental. and hemianopia,,may show that the glycosuria 8. In every case of glycosuria it is important is due to pituitary disease. A rarer lesion is to exclude hyperthyroidism, acromegaly or the basophil adenoma (Cushing syndrome), other endocrine disorder which might explain which causes obesity, hypertrichosis, genital this symptom without the presence of true atrophy, glycosuria, albuminuria and diabetes. hypertension. With the exception of the rare chromaffin Part II. The Treatment of tumour (hypersecretory adenoma) of the Glycosuria medulla, suprarenal disease is rarely associated Glycosuria being only a symptom, treatment with glycosuria, in spite of the effect of must be directed towards its underlying cause; 88 POST-GRADUATE MEDICAL JOURNAL Atp,il. 147 Postgrad Med J: first published as 10.1136/pgmj.23.258.185 on 1 April 1947. Downloaded from the prnciples of treatment being understood, restrictions later, when the patient w'B 'e less. the detailed management will depend upon the amenable. special features of each individual case. Balancing I. Diabetes Mellitus During. stabilization, the patient should be *The diagnosis being certain,. the ideal allowed as much normal activity as possible,. procedure is initially to stabilize..each case if complications.are absent and ketosis.slight. under hospital conditions. The essential Supposing that the diet needed is one of points are: 2,000 calories, one would start by giving a i. Permanent elimination from.the.urine of I,500 calorie diet; the following ..day, every trace of acetone, with due'attention to specimens of urine are.'obtained half-an-hour the detection and treatment of focal infections. before and' two 'hours after each of the three main meals: breakfast,' midday "meal and 2. Arrest, or reduction to a minimum, of supper. Each specimen is tested' for sugar and the loss of sugar in the urine. acetone and treatment, is determined by these These aims are fulfilled by giving a diet results. If acetone is present in, any specimen. .containing sufficient carbohydrate-to prevent in more than a trace, insulin should be started. the formation of acetone bodies and, if Details of insulin necessary, insulin to enable the patient to dosage will:be given later. utilize this, carbohydrate. At the end .of a week, the calorie' value of- the diet is increased and the insulin' dosage increased if necessary. Insulin.will be needed Diet permanently in every case showing persistent In planning the diet and mode of life of acetonuria and also when glycosuria 'of more a stabilized patient, it should be remembered than a moderate degree is continued. by copyright. that ' a happy diabetic is better than a s.ugar- Provided that the patient's renal threshold free man.' It is best to work with key' diets for glucose be known as a result of an initial devised by a specialist in dietetics. The follow- glucose tolerance test, it is not necessary to ing diets would be suitably balanced: make repeated blood sugar estimations during- Calories Carbohydrate Prrotein Fat treatment. When the patient is thought to be- (gms.) (gms.) (gms.) balanced, this may 1,500 120-150 8o 60-70 be confirmed by four-hourly- 1,750 170 8o 8o0 estimations of the blood sugar during one day,, 2,0o0 200 8o 90 e.g., at 8 a.m., I2 noon, 4 p.m. and 8 p.m. http://pmj.bmj.com/ 2,250 248 8o I00 The patient's calorie requirements can be Insulin judged sufficiently from his general appearance. If the urine picture, during stabilization A big, active man will need at least 2,300, a shows the need for insulin, it is best to start- sedentary worker 2jO00, most women i,750 by giving 5-10 units of soluble insulin at and some small people 1,500. Children, 6 a.m., 12 noon and 6- p.m. (half-an-hour especially adolescents, need proportionately before each meal). After four days the urine on September 29, 2021 by guest. Protected more calories and more protein. The vitamin picture is reviewed and as long as acetonuria content of the diet should be adequate, par- persists, each dose of insulin is inereased by ticularly as regards vitamins Bi and C. five units. When aceton has disappeared. The patient should be taught how to weigh and only sugar remains, it s best to allow a out his diet and, when balanced, he should week for spontaneous improvement ,before continue to'do this regularly on one day a week. making any further increase in insulin dosage. During stabilization, it is impossible to Week by week, the diet is increased until the decide whether a given case will prove to be patient is receiving his correct number. of mild or severe until the reaction to treatment calories, the insulin being concurrently in- can be seen. It is therefore better to begin creased until the urine picture is satisfactory. with a strict regime and then to slacken, Whenever possible, the total dose of insulin rather than to begin leniently and increase should finally be given as a' singie injection Atril. iA7 DIAGNOSIS AND TREATMENT OF GLYCOSURIA i89 Postgrad Med J: first published as 10.1136/pgmj.23.258.185 on 1 April 1947. Downloaded from before breakfast of Protamine Zinc insulin or III. Circulatory failure. Whether it be Globin insulin combined with soluble insulin. established or only threatening, this most Thus if a patient is balanced on soluble serious complication needs warmth, absolute insulin, 25, 20 and 25 units, this can be rest and circulatory stimulants, e.g., replaced by P.Z. insulin 40 units and soluble insulin 25 units each morning, the results Strophanthin gr. i/ ioo subcutaneously. being checked and dosage adjusted by urine Coramine 1-2 C.C., and blood sugar tests. Caffeine, gr., 3, A diabetic is considered to be balanced Adrenalin m. 3, when he is receiving his full complement of IV. Constipation is treated by enema or calories and not more than two of the six aperient. Drastic purgation may cause urine specimens of the day contain sugar. collapse. Before leaving hospital, the patient should Subsequent stabilization will be necessary. be able to give his own insulin, test his own urine and understand the nature of his complaint and it's chief risks, including Alimentary Glycosuria hypoglycaemia. These cases can usually be controlled by Diabetes is an outstanding example of the reducing the total amount of carbohydrate in need to study the patient as well as his disease. the day's diet and dividing what is allowed Mlost diabetics are fairly intelligent and equally between the four meals taken. The appreciate the fact that their future health will patient should be seen at regular intervals in depend largely upon their own co-operation. case diabetes supervenes, especially if he or

It is important to inculcate the idea that, she be over middle age. by copyright. with his diet and insulin maintained in order, a diabetic can live as a normal man and is not in any way to be considered as an invalid. 11. Renal Glycosuria Routine care and observation should be These patients should be kept on a suitably maintained at fortnightly and, later, monthly planned diet, in which the carbohydrate intervals. Children may need to be seen more content must be kept in the neighbourhood of often. I50-i8o gm. per day, equally divided between four meals. The calorie value should be made http://pmj.bmj.com/ good by extra protein and fat. If glycosuria' Diabetic Coma be not minimized in these p4tients, they tend Immediate treatment is needed for: to develop fuirunculosis and local pruritus. I. Ketosis. Any causative infection must be found and treated. Adequate therapy must III. Glycosuria of Cerebral Origin be given with glucose and soluble insulin, if on September 29, 2021 by guest. Protected necessary, by the intravenous route. The Treatment in each case is directed to the initial dose should be 50 units of soluble causative disease. insulin and 5ogm. of glucose, repeated 2-4 hourly as indicated by the urine picture. Some cases need as much as I,ooo units of IV. Endocrine Glycosuria insulin, covered by glucose, in the first 24 hours. I. Generalized lesions of the pancreas II. Dehydration. Fluid and salt loss should The possibility of a syphilitic fibrosis may be .made good by giving normal saline intra- have to be considered. If the Wassermann venously and by mouth without delay. Six reaction is found to be positive, the appropriate pints may be needed by slow drip over two treatment must be given. hours or longer. In pancreatitis of the chronic type, the diet Igo POST-GRADUATE MEDICAL JOURNAL April, I947 Postgrad Med J: first published as 10.1136/pgmj.23.258.185 on 1 April 1947. Downloaded from should be planned so that the patient receives a raised metabolism, it is unwise to restrict no more protein and fat than he can digest. their intake of carbohydrate. Carbohydrate should be given, as far as possible, as sugar, not as starch. In severe III. Acromegaly and pituitary basophilism pancreatitis and in haemochromatosis, insulin Treatment is by surgical measures when therapy will be needed. possible or by radiotherapy. The carbo- In pancreatic neoplasm the treatment is hydrate intake should not be unduly restricted surgical. pending treatment. IV. Suprarenal disease II. Hyperthyroidism. The glycosuria is usually The paroxysmal hyperglycaemia associated controlled by adequate treatment of the with the hypersecretory adenoma of the thyroid condition. Since these patients have medulla is cured if the tumour can be removed.

NERVE SUTURE By J. H. KIRKHAM, M.B., CH.B., F.R.C.S.(Ed.)

As there are no means yet available by In order to obviate this, the following which we can accelerate the regeneration of method has been adopted, and although theby copyright. nerves after their division, it follows that the opportunity for its employment has arisen best results can be attained only by so repair- in only two cases, the final results have been ing the site of division that conditions are so near perfection that I consider the method optimum for the natural downgrowth of the worthy of extended trial. It may be applied axons from the proximal end to the periphery.' to both primary and secondary nerve suture, It will be seen by anyone who has attempted although both the above cases were primary nerve suture that the usual method of end-to- sutures. end suture, by fine sutures through the sheath The nerve ends having been identified, they http://pmj.bmj.com/ only, tends to cause a bunching up of the axons are first trimmed square, preferably with very at the site of approximation and, in addition, sharp-pointed scissors in a primary suture or a varying number of axons from both distal a razor blade held in artery forceps in a and proximal ends protrude through the line secondary suture, as this causes minimal of anastomosis (Fig. i). trauma. No instrument is used to hold the The axons which protrude from the proximal nerve itself, and the sheath is best held in fine end will naturally become lost in the surround- conjunctival fixation forceps, or better still, on September 29, 2021 by guest. Protected ing tissues, and can never function again. iris forceps. The delicacy of touch required Those which protrude from the distal end will for the operation is equivalent to that necessary cause loss of the tubes of connective tissue and for the majority ofophthalmological operaticons. Schwann cells, by which means alone the The distal end of the sheath is then incised downgrowing axons from the proximal end longitudinally for about - in. at points dia- can attain their peripheral destinations, as metrically opposite to each other, the two the entrances to the tubes now lie outside the halves then being very carefully dissected nerve sheath. from the underlying nerve fibres and reflected This loss of the possible number of axons distally as two cuffs of sheath. It will then be which can ever reach the periphery must possible to cut back the nerve fibres X in. appreciably affect the perfection of the final further distally than the end of the sheath, result. thus leaving an empty tube of sheath i in.