Moshe Karp

Pregnancy outcome in patients with insulin-dependent diabetes mellitus with preconceptional diabetic control: A comparative study

Forty-four of 75 pregnant women with juvenile-onset insulin-dependent diabetes, who attended a preconceptional clinic, were seen regularly by a diabetologic team. Glycemic control was obtained by intensified insulin therapy and monitored by blood glucose self-monitoring. When these patients were compared with a group of 31 nonattenders of the preconceptional clinic, in the former normoglycemia and normal hemoglobin A1 values were achieved before conception, whereas in the latter good control was reached by the second trimester. This group had also more maternal complications, such as preeclampsia, and higher cesarean section rates. Congenital anomalies were 9.6% among offspring of nonattenders, while none occurred in those with preconceptional counseling. We confirm the evidence accumulated in the recent literature that congenital malformations in pregnancy complicated by diabetes may be linked to disturbances in maternal metabolism during the period of embryogenesis. Consequently we concur with the recommendation that tight diabetic control is required before the patient attempts to conceive.

The Prevalence of Cutaneous Manifestations in IDDM Patients and Their Association With Diabetes Risk Factors and Microvascular Complications

OBJECTIVE The aim of our study was to evaluate the frequency of skin manifestations, including the diabetic hand syndrome, in young IDDM patients. In addition, we studied the relation of the cutaneous manifestations to diabetes duration, glycemic control, and microvascular complications. RESEARCH DESIGN AND METHODS The frequency of skin manifestations, including the diabetic hand syndrome, were examined in 238 IDDM patients (disease duration >5 years) and 122 healthy control subjects in a cross-sectional study. In addition, we studied the relation of the cutaneous manifestations with diabetes duration, glycemic control, BMI, microvascular complications, and stratum corneum hydration using a stepwise logistic regression. RESULTS Diabetic skin manifestations were detected in 168 of 238 (71%) IDDM patients and in 18 of 122 (14%) of the control subjects. Ichthyosiform skin changes of the shins, scleroderma-like skin changes, tinea pedis, and dry scaly palms were detected in 48 vs. 7%, 39 vs. 0%, 32 vs. 7%, and 21 vs. 0.8% of the patients and control subjects, respectively. In the diabetic patients, a significant association was found between ichthyosis of the shins and sclerodermalike skin changes of the hand (P < 0.001) and between scleroderma-like skin changes and the skin dryness of the palms (P < 0.0001). When diabetic risk factors were considered, diabetes duration was significantly associated with scleroderma-like skin changes and ichthyosis of the shins (P < 0.0001). The latter was also found to be related to diabetic retinopathy (P < 0.0001). Keratosis pilaris was present in 21% of the patients versus 9% in control subjects and was found to be exclusively associated with high BMI. CONCLUSIONS Acquired ichthyosis is a common finding and the most prevalent skin manifestation in young IDDM patients. The development of several skin manifestations in insulin-dependent patients seems to be related to duration of diabetes and to development of diabetic microvascular complications.

Short- and long-range complications in offspring of diabetic mothers

The perinatal mortality rate of infants of diabetic mothers (IDMs) has declined dramatically from 250 per 1000 live births in the 1960s to a near-normal 20 per 1000 live births in the 1980s. Five to 8% of all IDMs suffer from major congenital malformations, and it is the latter that are responsible for 50% of these perinatal deaths. It has been shown that tight glycemic control prior to conception and during pregnancy can prevent an excess rate of congenital malformations, fetal macrosomia, birth trauma, and neonatal respiratory distress syndrome. We briefly review the short- and long-range complications that occur in offspring of diabetic mothers (ODMs) from gestation through young adulthood. Short-term neonatal complications, such as hypoglycemia, hypocalcemia, hypomagnesemia, hyperbilirubinemia, and polycythemia, are related mainly to fetal hyperinsulinemia, hypoxemia, and prematurity. They are readily controllable within the setup of modern neonatal intensive care units. Long-range complications include an increased rate of childhood and adolescent obesity, impaired glucose tolerance or diabetes mellitus, and subtle neuropsychological dysfunctions. These may be related to the severity of the maternal hyperglycemia during pregnancy, the consequent fetal hyperinsulinemia, and third trimester maternal lipid metabolism disturbances. Today we have at hand the knowledge and tools to properly treat both pregestational and gestational diabetes. Increased education of the general practitioner and the target population regarding early referral of pregestational diabetic mothers and the implementation of screening programs for gestational diabetes will further reduce diabetic pregnancy-related morbidity.

A Multidisciplinary, Comprehensive, Ambulatory Treatment Scheme for Diabetes Mellitus in Children

A study has been carried out on 262 children with juvenile diabetes and their parents, treated up to 10 yr on an ambulatory basis by a multidisciplinary team composed of pediatric endocrinologist, nurse, dietitian, psychologist, and social worker. Comparison of the findings with those of a study performed before inception of the Counselling Center for Juvenile Diabetics revealed the following positive influences: the degree of control attained was both higher and sustained with greater regularity; there were fewer complications with no episodes of coma, brittle diabetes, or severe ketoacidosis and almost no need for hospitalization; the attitude of the affected child, his parents, and his teachers was found to be considerably improved; there was better understanding of the nature of the disease and its requirements; the childs motivation to maintain the diabetic regimen was greater and conflicts within the family circle were markedly reduced; the childs self-concept was much higher; and both scholastic achievements and social adjustment were greater. We concluded that psychological stability is a basic factor in the control of diabetes, and the value of the multidisciplinary approach in the treatment of this chronic disease is indicated.

Crisis Intervention Program in Newly Diagnosed Diabetic Children

A group of 223 insulin-dependent diabetic patients, aged 7–24 yr, who had been under the regular care of our clinic up to 15 yr, were rated by two independent judges on a two-level scale of adjustment and maladjustment. The patients were divided into two groups. Group A (N = 107) comprised those who had been under care from diagnosis of the disease and had been subjected to the special crisis intervention program offered to every family upon referral of a newly diagnosed patient. Group B (N = 116) comprised patients who were diagnosed and treated initially in a clinic that had no crisis intervention program. Significant differences between the two groups were found in respect to three of the four aspects studied, i.e., compliance, familial relationships, and sociability, with group A showing a better adjustment than group B. There was no significant difference in the fourth aspect studied, i.e., school achievement and work performance. It was found that it took three times the effort, i.e., the time invested in counseling and psychotherapeutic measures, to bring group B to a good level of adjustment than it did to achieve similar results with group A. It is suggested that the initial period after diagnosis of diabetes in a child should be considered a period of crisis, requiring special muitidisciplinary services to reduce future psychosocial maladjustments and improve compliance.

Risk Factors for Development of Diabetic Nephropathy and Retinopathy in Jewish IDDM Patients

Risk factors associated with diabetic microvascular complications, with special reference to ethnic origin, were looked for in 231 young Jewish insulin-dependent diabetes mellitus (IDDM) patients with duration of diabetes ≥10 yr. Median age at diagnosis of diabetes was 9.2 yr (range 0.04–26.2 yr), and median duration of the disease was 15.3 yr (range 10.0–37.2 yr). Sixty-three percent of the patients were Ashkenazi Jews, and 37% were non-Ashkenazi Jews. HbA1 was evaluated every 3 mo in the last 10 yr of follow-up, and albumin excretion rate was tested in three 24-h urine collections. Direct and indirect ophthalmoscopy was performed every year since diagnosis of diabetes, and if retinal pathology was suspected, color photographs were taken. Microalbuminuria was detected in 31% and macroalbuminuria in 7% of the patients. Nonproliferative and proliferative retinopathy was found in 44 and 12% of the patients, respectively. On logistic regression analysis, two variables were significantly and independently associated with diabetic nephropathy—non-Ashkenazi origin and mean HbA1 values over the first 5 of 10 yr of follow-up. Variables significantly and independently related to diabetic retinopathy were non-Ashkenazi origin, mean HbA1 values over the last 10 yr of follow-up, and duration of diabetes. Because non-Ashkenazi Jews in Israel are of lower socioeconomic status than Ashkenazi Jews, we stratified our patients according to their socioeconomic parameters, median HbA1 values, and duration of diabetes. Non-Ashkenazi patients were at a higher risk to develop complications in all strata. We further stratified patients into four quartiles according to mean HbA1 values; there was a steep increase in the risk to develop macroalbuminuria in the 4th quartile of HbA1 (odds ratio [OR] 4.3 vs. 1.2 in the 3rd quartile) and proliferative retinopathy (OR 13.0 in the 4th quartile of HbA, vs. 2.8 in the 3rd quartile). We conclude that non-Ashkenazi Jewish IDDM patients are at significant risk to develop microvascular complications, independent of their glycemic control, duration of diabetes, and socioeconomic status. Careful follow-up and special efforts toward improving glycemic control should be focused on high-risk subgroups of patients.

The Incidence of Insulin-dependent Diabetes Mellitus in Israeli Children and Adolescents 0–20 Years of Age: A Retrospective Study, 1975–1980

A survey of the entire population of Israel revealed 392 newly diagnosed type I diabetic children and adolescents aged 0–20 for the period of 1975–80. The mean annual age specific incidence of type I (insulin-dependent) diabetes mellitus was 3.8/105 for the age group 0–14 yr and 4.2/105 for the age group 0–20 yr. The incidence among the Jews of Ashkenazi origin was 6.8 × 105 and that for Jews of non-Ashkenazi origin was 4.3 × 105, whereas that for the Arabs was 1.2 × 105. The overall incidence is lower than that reported for similar populations in most European countries, the USA, Canada, and New Zealand; similar to that reported for Arabs in Kuwait; and higher than only that found in Japan. The relative importance of environmental and genetic factors in the interpopulation differences in incidence of type I diabetes remains to be established.

Residual B cell function in diabetic children as determined by urinary C-peptide

SummaryC-peptide was determined in 24-h urine collections and in fasting plasma of 27 Type 1 (insulin-dependent) diabetic children (duration of disease 0–6 years) and in 11 matched normal children. Grouping the patients according to duration of disease from onset to 6 years, it was found that in the first year of disease the B cell reserve was a mean of 4.89±1.95 pmol · mg creatinine-1. 24 h-1 compared with a mean of 24.51±2.91 pmol · mg-1 · 24 h-1 in the control group. A further diminution was seen with increase in the duration of disease, until after 6 years when only traces of C-peptide could be detected. There was a good correlation between the levels of plasma C-peptide and urinary C-peptide values as related to creatinine (r = 0.89; p = < 0.001). In view of this, and since it is simpler and less traumatic to obtain frequent urine samples from children than it is to obtain blood samples, it was felt that the determination of urinary C-peptide constitutes a valuable tool in the evaluation of the diabetic child.

Preconceptional diabetes control in insulin-dependent diabetes mellitus patients with continuous subcutaneous insulin infusion therapy

Preconceptional diabetes management is an important prerequisite for pregnancy planning and its value has been well-documented. Glucose control and the outcome of pregnancy, managed in the preconceptional period, with continuous subcutaneous insulin infusion therapy to those receiving insulin injections are compared. Fifty-two juvenile onset insulin dependent diabetic women contemplating pregnancy were regularly consulted by a diabetology team starting at least two months before conception. Glucose control was achieved by continuous subcutaneous insulin infusion pumps (CSIIP) in 18 patients, and 34 women received intensive insulin therapy (IIT). In both groups, normal glucose levels and normal HbA1 were achieved at conception, maintained during the period of organogenesis and throughout pregnancy. In view of the fact that perinatal results, such as the occurrence of malformations, mean gestational age, mean birth weight and neonatal complications were not significantly different in both groups, we believe that both methods are equally effective. Consequently, the less costly and yet effective IIT may be the method of choice, while the more expensive pump should be used mainly in selected cases.

Pregnancy complicated by diabetic nephropathy

Diabetes mellitus is a high risk complication of pregnancy and this is particularly true whenever long standing diabetes is complicated by diabetic nephropathy. Five cases are reported of diabetic pregnancy complicated by nephropathy. Four women delivered healthy babies, and one patient aborted spontaneously in the 9th week of gestation. It is suggested that first and foremost in complicated diabetic pregnancy strict normoglycemia should be adhered to prior and all through pregnancy. Our findings based on these cases also suggest that: Pregnancy does not adversely affect the renal status of a diabetic woman or vice versa. Creatinine clearance is not worsened by the course of pregnancy in the majority of these patients and proteinuria per se does not add additional risks to pregnancy or outcome. Hypertension is a separate risk factor affecting the pregnancy despite normoglycemia. Motivation of these patients to maintain normoglycemia as well as bed rest for prolonged periods, intensive use of fetal monitoring, evaluation of fetal lung maturity and improved neonatal care may contribute to improved perinatal outcome.