Priscilla White

Pregnancy complicating diabetes

Following the introduction of insulin by F. G. Banting and C. H. Best in the early 1920’s, diabetes mellitus gradually became a relatively common complication of pregnancy. During the 1930’s and 1940’s, however, the reported mortality rate in the fetuses and neonates of women with this complication varied from almost nil to 70 per cent or more. To a great extent this variation resulted from differences in the severity of the disease and the degree of associated complications in those cases reported. White, of Boston’s Joslin Clinic, first brought some semblance of order into the reports of results with her clinical classification of diabetes based on the age at onset of the disease, its duration, and the presence of atherosclerotic vascular disease and renal complications. In addition, this classification allowed a partial prediction of the course of an individual diabetic patient during pregnancy and the chances for survival of the newborn infant. In 1952, White reported on the outcome of pregnancy in 278 diabetic women. Although 100 per cent of the infants of Class A patients were live-born, the survival rates of patients with clinically overt disease were as follows: Class B, 67 per cent; Class C, 48 per cent; Class D, 32 per cent; Class E, 13 per cent. (Joslin, E. P., Root, H. F., White, P., and Marble, A., editors: The Treatment of Diabetes Mellitus, ed. 9, Philadelphia, 1952, Lea 8c Febiger, Publishers, p. 676). In 1965, she added to the classification those patients with proliferating retinopathy (Class R) (Pregnancy and diabetes, medical aspects, Med. Clin. North Am. 49: 1015, 1965). Recently, the classification was modified further (Diabetes mellitus in pregnancy, Clin. Perinatol. 1: 33 1, 1974). White also contributed to knowledge of the newborn infant of the diabetic mother and of juvenile diabetes by presenting the classic description of the natural course of insulin dependency and neuropathic and vascular complications (Childhood diabetes, its course, and influence on the second and third generations. The Banting Memorial Lecture, Diabetes 9: 345,196O). Because of her leadership in the early diagnosis and rigorous management of prenatal care of women with this disease, White must be credited, to a great degree, with the decrease in the perinatal mortality rate from about 50 per cent three or four decades ago to 3 or 4 per cent at present.

Natural Course and Prognosis of Juvenile Diabetes

One thousand seventy-two juvenile patients of the Joslin Clinic have now lived for more than twenty years. Since in the United States today there are some one hundred thousand individuals who also are surviving childhood diabetes, a summary of the unique experiences of these long-term cases appears to be of value. What is their present status? Why did they develop diabetes? What was the entire course of their disease? How did they grow and mature? What complications did they develop? How did they die and, finally, what can be done toward the solution of their problems? Status. These 1,072 patients comprise 28.7 per cent of the 3,732 juvenile cases treated at the Joslin Clinic up to Aug. 1, 1955. Their present status shows that 82 per cent (879 patients) are living, 16 per cent (169 patients) have died, and 2 per cent remain untraced. Present age and duration. These patients are, of course, no longer children. The oldest (also treated by Dr. John Williams) at fifty-six years of age has survived his diabetic adolescence, youth, middle age, and is now entering the technical old-age period. The majority (61 per cent) are now between 30 and 39 years of age, with 18 per cent between ages 20 and 29, 20 per cent between ages 40 and 49, and 1 per cent now over age 50. The duration of diabetes to Jan. 1, 1956, or to death varied from 20 to 42 years; 70 per cent survived 20 to 29 years and 30 per cent over 30 years, including 3.2 per cent over 35 years. Achievements. Their struggle to survive and their struggle to achieve, even after the development of multiple disabilities, was amazing. A famous case of pituitary dwarfism, reported by Beck and Suter, totally blind and with renal failure, earned his PH.D . degree. A total comprising 30 per cent received college education; 5 per cent did graduate work. They achieved a high socio-economic level. Their occupations compared

Juvenile Diabetes Mellitus After Forty Years

Seventy-three patients with juvenile diabetes mellitus for a mean duration of 42.9 years were retrospectively studied on a nuiltidisciplinary basis. Only three of this group of patients were socially disabled as a result of their long-standing illness. Of all the complications, insulin-induced hypoglycemia was most common. Although diabetic retinopathy was clinically evident in about 75 per cent of patients, only 50 per cent of these seventy-three patients had a significant visual impairment. Nephropathy was apparent in 59 per cent of patients, and neuropathy was demonstrable in half of them. Significant peripheral vascular system impairment was present in 40 per cent and major cardiac complication in 20 per cent.

Pregnancy in Diabetes Complicated by Vascular Disease

Over 50 years of experience with pregnancy in diabetic women is reviewed. In particular, the maternal and fetal survival in mothers with either microvascular or macrovascular disease is considered. This includes White classes E, F, R, RF, H, and T. In this group of patients with vascular disease, maternal survival during pregnancy is virtually 100 per cent with the exception of class H (ischemie heart disease). Fetal survival has steadily improved throughout the time period examined, but is still considerably below that of pregnancies occurring in women without vascular disease. Long-term maternal survival is adversely affected by the first decade after delivery.

Use of female sex hormone therapy in pregnant diabetic patients

T HE inescapable conclusion that female sex hormone therapy gives added maternal and fetal protection when pregnancy complicates diabetes mellitus is based upon experience with more than 1,100 cases of diabetic pregnancies treated in the Joslin Clinic for over half a century. Among these 1,100 cases, assays for one or more of the female sex hormones of pregnancy have been determined in 780 viable pregnancies (completion of 28 weeks).

Pregnancy and diabetes.

Neuropathia Sciatic Diabetic: Reporto De Un Caso Es presentate un caso de extense neuropathia sciatic unilateral occurrente in un femina de cinquanta-nove annos de etate qui habeva diabete de un duration de vinti annos. Su symptomas se manifestava brevemente post le institution del therapia a insulina. In despecto de extense damnos motori e de sever grados de invaliditate in consequentia de hyperesthesias, ilia se restabliva gradualsed definitemente con un regime de cautemente regulate dieta, vitaminas supplementari, e exercitios therapeutic.

Patterns of Serum Immunoreactive Human Placental Lactogen (IR-HPL) and Chorionic Gonadotropin (IR-HCG) in Diabetic Pregnancy

Serum levels of immunoreactive human placental lactogen (IR-HPL) and chorionic gonadotropin (IR-HCG) were evaluated in eighty-four diabetic patients classified according to White. All patients in this group were treated with estrogen/progesterone therapy throughout pregnancy and were compared with a small group of twenty-seven diabetic patients not receiving hormonal therapy. In 164 normal pregnancies, serum IR-HPL is detected first at about six weeks and rises steadily to plateau levels of 6.2 ± 1.4 μg./ml. at thirty-five to thirty-seven weeks. In eighty-four diabetic pregnancies, the pattern of steady rise in IR-HPL levels simulates normal but the mean values are significantly greater than normal with peak values of 10.3 ± 4.7 /μg./ml. at thirty-five to thirty-seven weeks. Serum IR-HCG is first measured in normal pregnancy at about five to seven weeks by this assay, rises rapidly to peak levels of 163 ± 60 IU./ml. at eight to ten weeks and then falls to a nadir of 12.0 ± 2.0 IU./ml. at seventeen to nineteen weeks. Thereafter, there is a gradual secondary rise to a lesser mean peak value of 63 ± 19 IU./ml. at thirty-five to thirty-nine weeks. In diabetic pregnancy, the pattern of serum IR-HCG is similar to normal but with striking quantitative differences. The mean values in the second and third trimesters are significantly higher than normal with extreme variations among different pregnant individuals. The clinical implications of these abnormalities are not clear but suggest that the excessive secretion of HCG may mollify the diabetic imposition of early pregnancy whereas HPL contributes to the exaggerated glucose intolerance in late pregnancy.

Laboratory Assessment of Diabetic Pregnancy: A Brief Review

Pregnancy in the diabetic is at high risk. Recent efforts to improve perinatal mortality have principally been directed at establishing a laboratory assessment which could be used in the management of the diabetic pregnancy. Data on the hormones—estrogen, progesterone, human placental lactogen (HPL) and human chorionic gonadotropin (HCG) and on the enzymes—heat-stable alkaline phosphatase (HSAP) and diamine oxidase (DAO) are briefly reviewed for uncomplicated and for diabetic pregnancies.

Central retinal vein occlusion in juvenile diabetes; case report with consideration of the pathogenic relationship between diabetic retinopathy and retinal vein occlusion.

Abstract The occurrence of central retinal vein occlusion in juvenile diabetics is emphasized. Based on an unusual case report of a 15-year-old diabetic boy in whom diabetic retinopathy developed in one eye in immediate time-relationship of central vein occlusion in the other, the pathogenic relationship between these two conditions is discussed. The mechanism of the production of stasis in the venous retinal circulation in young diabetic individuals and in central retinal vein occlusion is outlined. A chronic condition of stasis in young diabetics appears to be brought about mainly by a distension of the venules as part of a pathophysiologic vasomotor reaction and intravascular aggregation of the red blood cells. It is suggested that a condition of stasis in the venous retinal circulation is a common pathogenic factor in the development of retinopathy and retinal vein thrombosis, and that this may explain the occurrence of central retinal vein occlusion in young diabetics.

The Young Diabetic Panel Discussion

Moderator White: The most important age periods in the management of the juvenile diabetic patient are infancy and adolescence. Some physicians dread the management of diabetes when the patient is under five years of age. The condition sometimes seems difficult to handle and it places extreme strain on the morale of the patients. Dr. Guest, what is your advice in regard to the diabetic infant? Dr. Guest: In my opinion diabetic infants are not necessarily more difficult to manage than older children. I should say that the age of adolescence is a much more difficult period than that of infancy, but then of course, other problems are involved. As most of you know, I recommend the so-called “free-diet-glycosuric” regime which is a subject of continuing debate. (See editorials in Diabetes: 1:487–89, Nov.-Dec. 1952.) In our clinic we have eighteen diabetic infants with onset of diabetes under the age of two years. Of these, eight were under one year of age when symptoms were first recognized. The youngest started glycosuria at nine days of age. The diagnosis was made by the astute mother because she had another diabetic child then aged one and onehalf years. When she noted the new infant was passing a lot of urine, she tested it and found sugar. On admission to the hospital, the babys blood sugar was 350 mg. per 100 cc. The urinalysis showed 3-plus glycosuria but no ketonuria. During twenty-four hours we determined the blood sugar every two hours and found it fluctuating between 300 and 500. Because there was no ketonuria, we felt that a period of observation before starting insulin would do no harm. After that brief period of observation the baby was given an initial dose of three units of protamine zinc insulin. During the next twenty-four hours the blood sugar fell progressively (determined at two-hour intervals) to 150 and then 100. Again, three units of protamine zinc insulin kept the blood sugar within normal range. (Let me stress the necessity for microchemical methods for following blood chemical changes in infants, whether diabetic or nondiabetic.) The baby was sent home on the fifth day, receiving two units of protamine zinc insulin daily. He was breast fed for ten months, on a demand schedule, with the dosage of protamine zinc varying from one to three units daily and solid foods offered at usual ages. (Please note that breast feeding is the ultimate in “free diet”, while it lasts!) That child is now seven years of age and has not suffered any illness that required hospitalization. His urine is rarely free of sugar, but excessive glycosuria with polyuria is likewise rare. Transient ketonuria has occurred occasionally during intercurrent infections, but has always cleared up promptly with the administration of extra doses of quick-acting insulin. The insulin requirement increased slowly with age and increasing body weight, from five units a day at one year of age, to thirty-five units (globin insulin) a day at the present time.