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A family of ten children is described. Five were hypothyroid and two had coeliac disease, both disorders coexisting in one child. IgA deficiency was present in the mother and one child.

Along term clinical study of semi-synthetic human monocomponent insulin (short and intermediate formulations) was undertaken in 32 patients with Type I diabetes. After a two-month run-in period, patients were randomised to either human or porcine insulin and blood glucose profiles and haemoglobin A1 were measured two monthly. Thirty-one patients (15—porcine, 16—human) have been treated for 12 months. There were no statistically significant differences between the two insulins in terms of fasting blood glucose (8.9±4.8 mmol/l porcine, 9.5±5.0 mmol/l human), haemoglobin A1 (10.4±2.6% porcine, 10.3±1.3 human), total daily dose (46.5±2.1 U porcine, 38.9±14.8 U human) or body weight (70.4±9.3 Kg porcine, 67.5±9.5 Kg human). Sera from both groups were tested for IgG binding to human and porcine insulin. In the patients treated with human insulin, binding to human insulin was 4.5±2.2μg/l at randomisation and 3.9±2.1 μg/l after six months. For the porcine group, binding to human insulin was 7.6±6.6 μg/l at randomisation and 7.8±7.2 μg/l after six months. These changes were not statistically significant. Thus no difference was found between patients treated with human or porcine insulin.

Twenty patients who had never previously received insulin were treated with a highly purified preparation (NPH LEO in R.I. quality). Insulin antibody estimations were performed over a 14 to 19 month period. Detectable amounts of antibodies were formed by 18 of the 20 patients. The levels were lower than those found in patients on conventional insulins but moderate levels were found in 7 patients. No correlation was found between the development of antibodies and changes in insulin requirement.

The association of diabetes mellitus and ‘stiff hands’ is well documented. We report on twenty-three cases of the syndrome and the incidence of diabetic complications in this group relative to controls matched for age, sex, duration of diabetes and therapy.

The early and long term complications of subtotal thyroidectomy in 306 hyperthyroid patients (multinodular goitre and diffuse hyperplasia) followed for up to 30 yr are reviewed. There were no perioperative deaths. Sixteen patients (5·2 per cent) had transient symptomatic hypocalcaemia, while 9 (2·9 per cent) had permanent hypocalcaemia. Permanent unilateral vocal cord paralysis occurred in 11 (3·6 per cent) patients (1·8 per cent of nerves at risk). Cumulative per cent (± s.e.m.) relapse and hypothyroid rates at 30yr (life-table analysis) were 15·6 ± 2·4 per cent and 20·5 ± 2·1 per cent, respectively. Lifelong follow-up of post-thyroidectomy patients is mandatory because of the risk of relapse or hypothyroidism.

A controlled trial of pen injection of insulin was performed in 78 patients, with assessment of metabolic control and lifestyle. After a 6-week run-in period, during which control was optimized, the patients were randomized, either to stay on a twice daily insulin regimen (n = 37), or to change to a three times daily pen regimen with human ultralente at night (n = 41). Over the 20 weeks, there was no significant change in mean glycosylated haemoglobin (syringe, mean +/- SD, 11.1 +/- 2.5% to 10.9 +/- 2.0%; pen, 11.3 +/- 2.6% to 11.2 +/- 2.0%), in blood glucose profiles or in frequency of hypoglycaemic attacks in either group. A self-completed questionnaire demonstrated high patient satisfaction with the pen injector (NovoPen), 78% for effect on lifestyle and 81% for increased flexibility. Ninety-five percent preferred the pen injector regimen to conventional treatment and stayed on it.

TWENTY-SEVEN insulin requiring diabetics, who had been treated with conventional non-purified insulins for at least four years, were transferred to a regimen of highly purified mixed species (porcine/bovine) insulin.

Pancreatic and salivary amylase/creatinine clearance ratios in patients with various degrees of renal impairment were compared with those obtained for control subjects. In chronic renal insufficiency (mean GFR 30 ml/min +/- 15 SD; n = 13) the clearance ratios for pancreatic (mean 3.5 +/- 1.85 SD) and salivary (mean 2.3 +/- 1.3 SD) amylase were significantly higher (P less than 0.05) than those in controls. Corresponding control values (n = 26) were 2.64 +/- 0.86 (pancreatic) and 1.64 +/- 0.95 (salivary). Three patients showed values above the normal limit. In the diabetic group (mean GFR 41 ml/min +/- 22 SD; n = 10) salivary amylase/creatinine clearance ratios (mean 2.36 +/- 1.55 SD) were significantly higher than in controls (P less than 0.05). Three patients showed raised values. Pancreatic amylase clearance was raised in only one of these patients. Three patients with terminal disease (mean GFR 10 ml/min) showed markedly raised (two- to threefold) clearance ratios for both salivary and pancreatic amylase. Of a total of 26 patients, eight had increased total amylase/creatinine clearance ratios. Pancreatic amylase/creatinine clearance was increased in seven patients, while nine patients showed raised salivary amylase/creatinine ratios. Patients with raised clearance ratios did not have clinical evidence of pancreatitis. We suggest that, in the presence of impaired renal function, a high amylase/creatinine clearance ratio need not be indicative of pancreatic disease.

Twenty-five patients presenting with intermittent claudication were studied with radionuclide arteriography to evaluate blood flow, capillary perfusion and left ventricular function. A comparison with the clinical presentation and contrast angiography showed that the radionuclide methods permitted a greater understanding of the physiological effects of ischaemia on the patient.

Sixty-six insulin-dependent diabetic patients with normal visual acuity were studied (132 eyes). The mean age was 27.7 years with a mean duration of diabetes mellitus of 8.7 years. Their mean electro-oculogram ratio, Arden grating and Munsell-Farnsworth scores were markedly abnormal (p much less than 0.00001). Background retinopathy was present in 53 eyes (40.2%), abnormal Arden grating scores (greater than 82) in 70 eyes (53%), abnormal Farnsworth-Munsell 100-hue score (greater than 100) in 88 eyes (56.7%), and 29 eyes (22%) had an electro-oculogram ratio less than 160. These abnormalities of retinal function did not correlate with retinopathy and were not secondary to it. Smoking caused a significant deterioration in contrast sensitivity.

Many authorities are currently suggesting specific strategies for optimal obstetrical management of pregnant diabetic patients which involve early admission, frequent monitoring and a high Caesarean section rate. The author suggests that a more conservative approach may be indicated. In support of this contention, he cites from his personal experience of managing over 1,000 diabetic pregnancies during the past 34 years. As there were no therapeutic abortions, the series is consecutive and unmodified. There were no maternal deaths, and the perinatal loss during the 34-year period was 7.4%. In the years 1979-1984 the perinatal loss in 285 viables was 4.5%, and the Caesarean section rate was 25.9%. In 87 primigravidae, the Caesarean rate was 31%.

A patient who developed hyperparathyroidism and osteomalacia causing a pathological fracture of the neck of the femur, with development of a neuropathy, while on long term phenytoin and phenobarbitone treatment is described.

The clinical outcome of 141 consecutive diabetic pregnancies managed in the National Maternity Hospital between January 1, 1979, and October 31, 1982, is described. Patients with gestational diabetes were excluded. There were 12 spontaneous abortions, and the perinatal mortality in 129 viable pregnancies was 31/1000. The malformation rate was 6.4%. Significant perinatal morbidity occurred in 20% of infants. The incidence of cesarean section was 20%. Spontaneous labor after 38 weeks occurred in 30% because there was a deliberate policy to allow all uncomplicated pregnancies to continue to term. This policy had benefits for the infant as well as the mother because there was a notable reduction in neonatal morbidity. Possible explanations of high cesarean section rates in other centers are discussed.(Obstet Gynecol 62:279, 1983)

Seventy-seven pregnancies (79 infants) complicated by hyperthyroidism were seen at three Dublin Maternity Hospitals during a 25 year period. Hyperthyroidism was diagnosed following conception in 14 pregnancies. Treatment was with carbimazole alone in 73 pregnancies, in a usual dose of 5 to 10 mg daily. The total fetal loss was 15.2 per cent with a perinatal loss of 5.1 per cent. The perinatal loss in patients treated with carbimazole alone was 4.1 per cent (excluding one death due to congenital malformation). Four infants (5.1 per cent) had goitre and 57 (85.1 per cent) of the surviving infants were above the 25th centile for gestational age. Spontaneous premature labour occurred in 7 pregnancies (9.1 per cent). There was a relative excess of infants with a birth weight less than the 25th centile, of neonatal goitre and premature labour after pregnancy in which treatment was started following conception. Hyperthyroidism complicating pregnancy can be treated effectively with antithyroid drugs given alone and in the minimal effective dose.

Goitre is common and alterations in biochemical indices of thyroid function are invariable during pregnancy , but thyroid disease, of which hyperthyroidism is the most frequent (0,05% of 72,257 pregnancies at three Dublin Maternity Hospitals, 1979-81) is rare. Good results in terms of perinatal loss (4/112, 3.57%) has been achieved by one of us (MID) in 109 pregnancies using antithyroid drugs alone. Neonatal thyrotoxicosis occurs in one to two percent of babies born to mothers with thyroid disease. The condition is usually transient but a prolonged course may occur in up to 20 percent. Successful pregnancy is possible despite maternal hypothyroidism; three such pregnancies have been managed by one of us (MID). Clinical hyperthyroidism due to trophoblastic disease is very rare and is cured by evacuation of molar tissue. The course of thyroid cancer is not affected by pregnancy.

CLASSIFICATION by cause provided the basis for appropriate adjustment in treatment of 30 insulin treated diabetics, e.g.

Twenty patients with primary idiopathic haemochromatosis were tissue typed. HLA-A3 and B7 were increased in frequency. The significance of these findings in relation to other studies is assessed.

The efficacy of our current educational programme for diabetic patients was assessed. Cognitive and behavioural tests were administered to 75 Type 1 (insulin-dependent) diabetic patients, aged less than or equal to 30 years attending the Diabetic Clinic of the Mater Misericordiae Hospital, Dublin, Ireland. An overall deficiency in knowledge was evident. Fifty-one patients responded incorrectly to greater than 20% of the items tested. Twenty-nine patients lacked the ability to communicate a simple understanding of diabetes. Whereas most (70 +) correctly identified the methodology of urinalysis, uncertainty was evident concerning appropriate action needed in response to such tests. Forty-nine did not know the significance of thirst and polyuria and 20 were unaware that hyperglycaemia could progress to coma. The ability to modify insulin dosage was poor as was the ability to use exchanges. Of patients aged greater than or equal to 20 years, those from the Dublin region scored better than did those from surrounding towns or rural areas, (r = 0.5; p less than 0.01). Regular out-patient attenders scored less well than non-attenders (r = 0.24; p less than 0.05) but had better glycosylated haemoglobin levels (r = 0.3; p less than 0.01). Gycosylated haemoglobin showed no significant correlation with level of knowledge held.

Summary Among a diabetic clinic population of 5,000 there were 113 patients (1.1%) with concurrent clinical thyroid dysfunction (56 hyperthyroid, 57 hypothyroid). Seventy-one (62.8%) of these patients were insulin-dependent and diabetes preceded thyroid disease in 85 (75.2%). Twenty patients were given carbimazole for two or more years and of these 15 (75%) relapsed, a percentage not significantly different from that seen in non-diabetic patients. The value of screening diabetic patients for evidence of thyroid dysfunction is discussed.

This propective study was undertaken to evaluate serial measurements of glycosylated haemoglobin (HbA1) as an index of control in diabetic pregnancy. Glucose and haemoglobin A1 were measured at weekly intervals throughout 88 pregnancies. Levels of HbA1 and glucose correlated significantly. Elevated HbA1 levels in the second and third trimester and postnatally were associated with hydramnios. Other obstetrical complications were too few to permit meaningful correlations. Smoking practice was associated with raised mean HbA1 levels in the first and second trimester. In patients of White’s Class A, smoking was strongly associated with lower birth weight and weight centile. Foetal loss (abortion, stillbirth) or malformation correlated significantly with the mean HbA1 overall and with the mean HbA1 in the second trimester. Although the number of neonatal complications pertaining to an individual baby correlated with the mean HbA1 overall and with the mean HbA1 in the third trimester neither neonatal hypoglycaemia nor hyperbilirubinemia showed a correlation. Levels of HbA1 correlated with skinfold thickness but not with baby weight. The value of HbA1 as an index of diabetic control in pregnancy is discussed.

Esophageal function in 20 subjects with diabetes mellitus was assessed using esophageal manometry, 24-hr ambulatory esophageal pH monitoring, and esophageal scintigraphy. Seven patients had abnormal esophageal manometric studies, and this abnormality was significantly associated with peripheral neuropathy. Almost half of the subjects studied demonstrated excessive gastroesophageal acid reflux, but there was no correlation between the likelihood of abnormal reflux and the presence of peripheral neuropathy. Esophageal scintigraphy was relatively insensitive in the detection of abnormal esophageal function in diabetics.

The distribution of HLA antigens in a group of Irish patients with hyperthyroidism was studied, in an attempt to define whether specific antigens were associated with relapse of the disease following medical therapy. The increase in HLA-B8 and DR3 found by others in this disease was confirmed, but no difference in HLA type was documented in 33 patients who had relapsed compared to 24 who had not relapsed. Forty-six per cent of the relapsed group were DR3 as against 45% of the non-relapsed group.

A review of the outcome of treatment by subtotal thyroidectomy, radio-iodine and carbimazole of 837 patients with hyperthyroidism seen consecutively over the period 1954--78 inclusive is presented. The age and sex distribution, the male to female ratio, the ABO blood group distribution and the prevalence of pernicious anaemia and diabetes mellitus in these patients was also analysed. Life-table data showed that the five-year and ten-year cumulative relapse rates following a two-year course of carbimazole (n = 162) were 56 per cent and 62 per cent; following surgery (n = 266), 6 per cent and 10 per cent and following radio-iodine (n = 43), 3 per cent and 14 per cent. Five-year and ten-year cumulative hypothyroid rates after surgery were 10 per cent and 18 per cent, and after radio-iodine 10 per cent and 30 per cent. Hypothyroidism did not occur after carbimazole therapy. Of 31 patients who took carbimazole for less than two years (mean 11 months, range 6--19 months), 91 per cent had relapsed at five years. Of 79 patients treated for longer than two years (mean 3.8 years, range 2 1/2--14 years), relapse rates at five and eight years were 49 per cent and 62 per cent. Nine patients (3.4 per cent) suffered permanent vocal cord paralysis and five (1.9 per cent) had permanent hypocalcaemia. The male/female ratio was 9.9 to 1, with a peak female prevalence between 25 and 30 years and a peak male prevalence between 40 and 45 years. The ABO blood group distribution among patients did not differ significantly from the distribution in the general population (chi 2 = 13.4, p = 0.2). Forty-seven patients (5.6 per cent) had diabetes mellitus and thyrotoxicosis whilst two patients (0.23 per cent) had diabetes, thyrotoxicosis and pernicious anaemia.

Early recognition of Reye’s syndrome is important as prompt treatment may reduce morbidity and mortality. We report a case where the syndrome presented as ketoacidosis in a known diabetic.

Master, Colleagues, Ladies and Gentlemen, I am grateful for the honour you have done me in inviting me to give the Ninian Falkiner Memorial Lecture for 1982.

In a consecutive series of 600 pregnancies (618 infants) in 300 clinically diabetic patients, treated in Dublin, Ireland, the maternal mortality was 0 and the loss of viable infants was 9.5%. Therapeutic abortion and sterilization were not practiced. The cesarean section rate was 23%. The major causes of perinatal loss were hyaline membrane disease and congenital malformations. Recent routine estimation of the L/S ratio in amniotic fluid led to a reduced incidence of respiratory distress syndrome and a consequent improvement in perinatal mortality. At a very early stage in pregnancy diabetic patients should be referred to a center in which physician, obstetrician, nurse, and pediatrician operate as a team. Strict control of diabetes is essential.

Eight patients with necrobiosis lipoidica diabeticorum, in association with diabetes mellitus, were seen in the past 14 years out of a diabetic clinic population of 2,000. These patients are evaluated and the histological appearances of skin biopsies are discussed. The most recent literature on the aetiology, histological features and relationship to diabetes mellitus of N.L.D. is discussed. The value of cortisone modified glucose tolerance testing in patients presenting with N.L.D. lesions is emphasized. That the classical clinical presentation is often difficult to substantiate histopathologically is apparent from the detailed studies reported in the literature and reviewed briefly.

Summary Glycosuria, a family history of diabetes mellitus, a history of previous unexplained fetal loss or of large babies may indicate possible latent diabetes in pregnancy. The value of the oral glucose tolerance test in detecting latent diabetes in an antenatal clinic over a five-year period is reviewed and 220 women with latent diabetes were observed in 293 pregnancies. The fetal loss in 244 viable pregnancies in which latent diabetes was recognized prior to delivery was 2.9 per cent. The cortisone modified glucose tolerance test employed after the puerperium in 108 of the women was of less diagnostic value as a test for latent diabetes than pregnancy itself.