Lars Mølsted-Pedersen

Oral hypoglycaemic agents in 118 diabetic pregnancies

SUMMARY

Predictive factors for the development of diabetes in women with previous gestational diabetes mellitus.

OBJECTIVES: The purpose of this study was to determine the incidence of diabetes in women with previous dietary-treated gestational diabetes mellitus and to identify predictive factors for development of diabetes. STUDY DESIGN: Two to 11 years post partum, glucose tolerance was investigated in 241 women with previous dietary-treated gestational diabetes mellitus and 57 women without previous gestational diabetes mellitus (control group). RESULTS: Diabetes developed in 42 (17.4%) women with previous gestational diabetes mellitus (3.7% insulin-dependent diabetes mellitus and 13.7% non—insulin-dependent diabetes mellitus). Diabetes did not develop in any of the controls. Predictive factors for diabetes development were fasting glucose level at diagnosis (high glucose, high risk), preterm delivery, and an oral glucose tolerance test result that showed diabetes 2 months post partum. In a subgroup of previous patients with gestational diabetes mellitus in whom plasma insulin was measured during an oral glucose tolerance test in late pregnancy a low insulin response at diagnosis was found to be an independent predictive factor for diabetes development. CONCLUSIONS: Women with previous dietary-treated gestational diabetes mellitus have a considerably increased risk of later having diabetes. Follow-up investigations are therefore important, especially in those women with previous gestational diabetes mellitus in whom the identified predictive factors are present.

Significant decrease in congenital malformations in newborn infants of an unselected population of diabetic women

In an unselected and consecutive series of 1858 newborn infants of diabetic mothers, born in the Rigshospital, Copenhagen, in the period 1967 to 1986, congenital malformations were studied. The malformation rate in White Classes B to F was remarkably constant from 1967 to 1981, but a significant decrease in major congenital malformations was found in the period 1982 to 1986 versus 1977 to 1981 (2.7% vs. 7.4%, p p p > 0.05). Seventy-five percent of the diabetic pregnancies were planned, and in these pregnancies only 1% of the infants had major congenital malformations. The frequency of fatal malformations in White Classes B to F was still significantly higher than in the control group ( p

Screening for gestational diabetes mellitus by a model based on risk indicators: A prospective study

OBJECTIVE This study was performed to prospectively evaluate a screening model for gestational diabetes mellitus on the basis of clinical risk indicators. STUDY DESIGN In a prospective multicenter study with 5235 consecutive pregnant women, diagnostic testing with a 2-hour 75-g oral glucose tolerance test was routinely performed in women with risk indicators and offered to women without risk indicators as part of the study. RESULTS Forty-four percent of the women underwent testing, 43% declined participation, 6% did not speak Danish, and 7% could not be contacted. By extrapolation of the results from tested women to the whole group in question, a 2.4% prevalence of gestational diabetes mellitus was calculated. Sensitivity and specificity of the model was 80.6 (73.7-87.6) and 64.8 (63.5-66.1), respectively (95% CIs). CONCLUSION Under ideal conditions, sensitivity of the model was comparable with universal screening by fasting glucose or a 1-hour 50-g glucose challenge test. Both screening and diagnostic testing could be avoided in two thirds of all pregnant women.

Assessors of Fetal Perinatal Mortality in Diabetic Pregnancy: Analysis of 1,332 Pregnancies in the Copenhagen Series, 1946–1972

In a series of 1,332 pregnancies in women with diabetes, perinatal fetal mortality varied in a statistically significant degree, with maternal factors and pregnancy complications expressed respectively, by the White and PBSP classifications. Also, mortality declined steadily over the years 1946 to 1972. Fatal congenital malformation was the most important single cause of perinatal death in recent years. A controlled trial must take into account the year of admission as well as the White and PBSP classifications; with the prevailing low and decreasing mortality, even large centers may be unable to fulfill the requirements as to sample size within a few years. Therefore, criteria other than perinatal mortality may be needed to assess the value of changes in treatment.

Prevalence and predictive value of islet cell antibodies and insulin autoantibodies in women with gestational diabetes.

The objective of the present study was to investigate the predictive value of islet cell antibodies (ICA) and insulin autoantibodies (IAA) for development of diabetes in women with previous gestational diabetes (GDM). Two hundred and forty‐one previous diet‐treated GDM patients and 57 women without previous GDM were examined 2–11 years after the index pregnancy. In subgroups, plasma from the diagnostic OGTT during index pregnancy was analysed for ICA and IAA. Among the previous GDM patients, 3.7% had developed Type 1 diabetes and 13.7% Type 2 diabetes. Four (2.9%) of the 139 GDM patients tested for ICA were ICA‐positive and three of these had Type 1 diabetes at follow‐up, as well as three ICA‐negative patients. The sensitivity, specificity, and predictive value of ICA‐positivity for later development of diabetes were 50%, 99%, and 75%, respectively. None of the women was IAA‐positive during pregnancy. In conclusion, the majority of the patients with GDM did not show evidence of ongoing autoimmune destruction of the beta cells during the index pregnancy. However, ICA‐positive GDM patients had a high risk of developing Type 1 diabetes later in life.

Early growth delay in diabetic pregnancy: relation to psychomotor development at age 4

Ninety nine consecutive insulin dependent and 101 non-diabetic pregnant women were examined by ultrasonograph to assess early fetal growth. In 42 of the diabetic mothers and three of the non-diabetic mothers the scan showed early intrauterine growth delay. At 4-5 years of age all children available for study were evaluated by the Denver developmental screening test. Only 23 of the 34 children of diabetic mothers with early intrauterine growth delay had normal test scores compared with 46 of the 50 children of diabetic mothers with normal intrauterine growth. The children failed in personal-social development, gross motor development, and particularly in language and speech development. Children of diabetic mothers with normal early fetal growth had scores very similar to those of the children of non-diabetic mothers, of whom 76 of the 86 tested had normal scores. This study suggests that children with a history of growth delay in early diabetic pregnancy should be screened for possible developmental impairment.

Increased incidence of true type I diabetes acquired during pregnancy.

A longitudinal study was carried out of all patients with newly acquired insulin dependent diabetes during pregnancy (as distinct from non-insulin-dependent gestational diabetes) seen at the Copenhagen Centre for Diabetes and Pregnancy during 1966 to 1980. The series comprised 63 patients with a mean age of 27 (SEM 1) years. At diagnosis the mean fasting blood glucose concentration was 15.6 (1.3) mmol/l and mean maximal insulin dose 49 (3) IU/day. At a prospective follow up examination a mean of 8 (SEM 1) years after diagnosis 46 of 60 patients (77%) were being treated with insulin (35 (2) IU/day) and had a very low mean stimulated plasma C peptide value (0.12 (0.02) nmol/l) suggesting absent or nearly absent beta cell function. The remaining 14 patients (23%), not currently receiving insulin, appeared to be severely glucose intolerant, having a mean fasting blood glucose concentration of 13.4 (1.2) mmol/l. Thus most of these patients developing insulin dependent diabetes during pregnancy had true type I disease. Compared with the age specific incidence of type I diabetes in the background population of women the incidence was at least 70% higher in pregnant than non-pregnant women (p less than 0.001; chi 2 = 11.6; f = 1). This increased incidence occurred in the third trimester when the risk of developing type I diabetes was 3.8 times that of non-pregnant women (p less than 0.000001; chi 2 = 35.6; f = 1). Finally, the risk of developing insulin dependent diabetes during pregnancy was lower when conception occurred in the winter (p less than 0.05; chi 2 = 4.18; f = 1).

Perinatal complications in women with gestational diabetes mellitus

Background. The aim of the study was to examine the outcome of the pregnancy and neonatal period in 1) women with gestational diabetes mellitus and non‐diabetic pregnant women, and 2) in women with early and late diagnosis of gestational diabetes mellitus.

Adverse pregnancy outcome in women with mild glucose intolerance: is there a clinically meaningful threshold value for glucose?

Background. The diagnostic criteria of gestational diabetes mellitus (GDM) have been based on the risk of future maternal diabetes rather than the short‐term risk of mother and infant. Our aim was to illustrate the relation between various adverse pregnancy outcomes and maternal glucose levels in women with mild glucose intolerance using a graphical approach. Methods. Observational study of 2,885 pregnant women examined with a 2‐h, 75‐g oral glucose tolerance test (OGTT) based on risk indicators. Only women with 2‐h capillary blood glucose <9.0 mmol/l were included, as women with 2‐h values ≥9.0 mmol/l were treated for GDM. Empirical frequencies of adverse outcomes were related to 2‐h values by linear and quadratic logistic models. Adjustments for well‐known confounders were performed by a multiple logistic model. Results. Linear trends were demonstrated for the outcomes: shoulder dystocia, caesarean section rate (univariate analysis only), spontaneous preterm delivery, and macrosomia (large‐for‐gestational age infants). None of the outcomes deviated significantly from linearity. No significant trend was found for hypertension or neonatal hypoglycaemia and jaundice. Conclusions. A gradually increasing risk for a number of adverse pregnancy outcomes was found with increasing glucose levels. No obvious threshold value for GDM was demonstrated for 2‐h values up to 9.0 mmol/l.