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PAPERS: Inge M Evers, Harold W de Valk, and Gerard H A Visser Risk of complications of pregnancy in women with type 1 diabetes: nationwide prospective study in the Netherlands BMJ 2004; 328: 915 [Abstract] [Full text]

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This may be due to low DHEA...

James M. Howard   (16 April 2004)

Pregnancy in women with type 1 diabetes: treatment

Antonio Marini, Massimo Agosti, Marua Li Destri, Francesco Cattaneo   (27 April 2004)

Risk of complications of pregnancy in women with type 1 diabetes: Ophthalmic aspect

Sachin M Salvi   (1 May 2004)

Could increased maternal and foetal complications of pregnancy reflect hitherto undiagnosed coeliac disease?

Alastair D Smith   (12 June 2004)

This may be due to low DHEA... 16 April 2004
James M. Howard, independent biologist 1037 North Woolsey Avenue, Fayetteville, Arkansas 72701-2046, U.S.A. Send response to journal: Re: This may be due to low DHEA...	It is my hypothesis that DHEA was selected by evolution because it optimizes replication and transcription of DNA. Therefore, all tissues are dependent upon DHEA for optimal growth and development. A mother produces DHEA for herself and her fetus. Diabetes has been linked to low DHEA and DHEA has been used to ameliorate problems of diabetes. Therefore, a diabetic mother whose symptoms have been regulated has not had her DHEA levels corrected. This does not correct the amount of DHEA necessary for the mother and fetus. I suggest it is low DHEA that is involved in continued "maternal and perinatal complications," vis-à-vis successful treatment of maternal diabetes. Competing interests: None declared
Pregnancy in women with type 1 diabetes: treatment 27 April 2004
Antonio Marini, professor of pediatrics (neonatology) Istituto di Pediatria e Neonatologia, University of Milan, Via della Commenda, 9 - 20122 Italy, Massimo Agosti, Marua Li Destri, Francesco Cattaneo Send response to journal: Re: Pregnancy in women with type 1 diabetes: treatment	EDITOR - Evers et al showed that even with a good control, based on HbA1c, immediate results in diabetic pregnancy (DP) are not fully satisfactory, in some way indicating a more stringent metabolic control for DP (1). This is correct. However short term results must be out weighted versus long term evaluation in offsprings of DP. Many years ago very good result for the fetus and the neonate, reached with a very tight metabolic control (VTMC), obtained with a maximal tolerated dose of insulin, were presented (2). However the VTMC induced a fetal constrain, namely in male subjects, with a birth weight 200-300 g lower than expected for the normal population. In these neonates also low normal insulin secretion and a reverse glucagon output were noticed after i.v. glucose challenge (3). In fact when we did a long term evaluation (12-33 years of age) in offsprings of DP, kept under VTMC, a much higher incidence of obesity (50%) than expected, with an increase of insulin resistance and an high frequency (10%) of juvenile type 1 diabetes were observed (4, 5). These data, based on an untoward human experiment, are worst in comparison to other long term evaluation for offsprings of DP kept under a more loose control (6, 7). There is suspicion that the mother's VTMC can cause a certain degree of fetal pancreatic beta cells hypoplasia and are in line with Barker’s hypothesis (8). Probably an intermediate way of treatment of DP, avoiding both macrosomia and fetal constraint, should satisfy immediate and long term results (9, 10). But for the latter evaluation we must wait for many years. 1. Evers IM, de Valk HW, Visser GHA. Risk of complications in pregnancy in women with type 1 diabetes: nationwide prospective study in the Netherlands. BMJ 2004; 328: 915-8. 2. Roversi GD, Gargiulo M, Nicolini U et al. A new approach to the treatment of diabetic pregnant women. Am J Obstet Gynecol 1979; 135: 557- 76. 3. Marini A, Cattaneo F. Control of diabetes in pregnancy and metabolism alterations in the neonate. Acta Paediatr 1998; 87: 711. 4. Marini A, Dozio N, Li Destri M, Cattaneo F. Short and long term results on offsprings of diabetes mothers, kept under a very tight metabolic control during pregnancy. IV. Correlations between insulin resistance and birth weight. Pediatr Res 2001; 50 (1) suppl.: 19A. 5. Marini A, Li Destri M, Cattaneo F, Dozio N. Short and long term results on offsprings of diabetic mothers, kept under a very tight metabolic control during pregnancy. V. Incidence of juvenile type 1 diabetes. Pediatr Res 2001; 50 (1) suppl.: 20A. 6. Plagemann A, Harder T, Kohloez R, Rode W, Dorner G. Glucose tolerance and insulin secretion in children of mothers with pregestational IDDM or gestational diabetes. Diabetologia 1997; 40: 1094-100. 7. Silverman BL, Rizzo TA, Cho NH, Metzger BE. Long term effects of the intrauterine environment: the Northwestern University Diabetes in Pregnancy Center. Diabetes 1998; 21: 142B-149B. 8. Hales CN, Barker DJ. Type 2 (non-insulin-dependent) diabetes mellitus: the thrifty phenotype hypothesis. Diabetologia 1992; 35: 595- 601. 9. Mello G, Parretti E, Mecacci F et al. What degree of maternal metabolic control in women with type 1 diabetes is associated with normal body size and proportions in full-term infants? Diabetes Care 2000; 23: 1494-8. 10. Langer O, Conway DL, Berkus MD et al. A comparison of glyburide and insulin in women with gestational diabetes mellitus. N Engl J Med 2000; 343: 1134-8. Competing interests: None declared
Risk of complications of pregnancy in women with type 1 diabetes: Ophthalmic aspect 1 May 2004
Sachin M Salvi, SpR (LAT) Ophthalmology Royal Glamorgan Hospital, Cardiff Road, Newport NP20 2UB Send response to journal: Re: Risk of complications of pregnancy in women with type 1 diabetes: Ophthalmic aspect	Editor- The study by Evers, de Valk and Visser(1) has contributed that despite overall adequate glycaemic control, maternal complications remained high in women with type 1 diabetes. One important factor, though not looked for specifically in the study, is the similar effect of pregnancy on diabetic retinopathy in type 1 diabetics. We feel it is extremely important to monitor diabetic retinopathy in pregnancy. Pregnancy is a risk factor for development and progression of retinopathy in women with diabetes(2). The prevalence of retinopathy in diabetic pregnancies is 10-27%(3). There is nearly 10% risk of developing diabetic retinopathy even if none is present before pregnancy. The duration of diabetes before onset of pregnancy is the prime risk factor for the presence, severity, and progression of retinopathy during pregnancy(4). Progression of retinopathy is also associated with early onset of diabetes, high retinopathy level, hypertension, proteinuria, nulliparity, suboptimal glycaemic control before pregnancy, and rapid normalization of hyperglycemic blood glucose levels during pregnancy. Though, it is essential to get diabetes under control in poorly controlled diabetics, sudden strict control can be associated with worsening of diabetes, which sometimes may not recover even after pregnancy. Hence we recommend good control of diabetes before pregnancy and maintained throughout pregnancy. Patients who go on to develop sight threatening proliferative diabetic retinopathy need to be promptly treated with laser panretinal photocoagulation. In the experience of Mr Chris Blyth, Consultant Medical Retina Specialist at Royal Gwent Hospital, there should be a low threshold for laser if proliferative diabetic retinopathy develops in pregnancy especially as many patients after delivery have a high DNA rate from clinics due to commitment to the child leading to suboptimal follow up and consequential worsening of diabetic retinopathy. Patient with previously treated proliferative diabetic retinopathy laser do not generally worsen during pregnancy. Hence once the proliferative diabetic retinopathy has been treated, there is no reason ophthalmologically against further pregnancy as long as the patient is monitored carefully. We suggest that patients of child bearing age with type 1 diabetes planning pregnancy should be warned about the potential ophthalmic problems associated and monitored closely by suitably trained personnel: 1. Prior to pregnancy for counselling 2. Early in 1st trimester 3. Each trimester or more frequently if indicated 4. six weeks post partum Close monitoring and prompt treatment can help us reduce the maternal ophthalmic complications of type 1 diabetes in pregnancy. References: 1.Evers IM, de Valk HW, Visser GHA. Risk of complications of pregnancy in women with type 1 diabetes: nationwide prospective study in the Netherlands.BMJ 2004; 328:915-8 2.Davidorf FH, Chambers RB: Diabetic retinopathy during pregnancy. Clin Perinatol 1993; 20:571-581 3.Hadden DR: Diabetes in pregnancy. Diabetologia 1986; 29:1-9 4.Sunness JS: The pregnant woman's eye. Surv Ophthalmol 1988; 32:219-238 Competing interests: None declared
Could increased maternal and foetal complications of pregnancy reflect hitherto undiagnosed coeliac disease? 12 June 2004
Alastair D Smith, Assistant Professor of Medicine, Division of Gastroenterology and Hepatology Rm 105, Bell Research Building, Trent Drive, Duke University Medical Center, Durham. NC. 27710. USA. Send response to journal: Re: Could increased maternal and foetal complications of pregnancy reflect hitherto undiagnosed coeliac disease?	Editor: The findings of Evers et al among women with type 1 diabetes mellitus (DM) in respect of maternal and foetal complications of pregnancy are striking. 1 It occurred to me that one potential explanation for their results could be an increased prevalence of as yet undiagnosed coeliac disease (CD). The reported prevalence of CD among patients with type 1 DM ranges from 0.97% to 16.4%. 2 Although reasons for this disparity are not entirely clear, recent data from Europe and North Africa respectively have confirmed a prevalence of CD in type 1 DM patients of 8.3% and 10.3%. 3, 4 Thus, assuming a 9% prevalence rate of CD in Evers and colleagues’ study population, this would account for 27 affected, albeit undiagnosed patients. (There is no suggestion from data presented that CD occurred with greater frequency among patients with type 1 DM, although this information may not have been sought specifically at interview, nor that serum folate concentrations were estimated among study patients.) Results from several studies have suggested an association between hitherto undiagnosed, and therefore untreated CD, and low infant birth weight (<2,500g), intra-uterine growth retardation (IUGR), and rates of spontaneous abortion, recurrent abortion, and stillbirth. 5 Furthermore, the same studies demonstrated that adherence to a gluten free diet reduced the risk of these maternal and foetal complications of pregnancy to a level that was not different from subjects without CD. However, recent data from a prospective, Italian, population-based study involving just over 5000 pregnant women has challenged these findings. 6 Greco et al demonstrated a prevalence (1:100) of serologic results consistent with CD among hitherto undiagnosed patients, (small bowel biopsy was not permitted in pregnant women by the regional ethics committee) in whom rates of spontaneous abortion, IUGR and mean birth weight were not statistically different from values observed among patients without serologic evidence to suggest CD. Therefore, even though the prevalence of CD among this cohort of pregnant Dutch women with type 1 DM was not reported, it seems unlikely that hitherto undiagnosed CD could account for the excess maternal and foetal complications of pregnancy. Not only are pregnancy complications described among patients with untreated CD largely different from those reported in this study, but CD may not be the risk factor for poorer maternal and foetal outcomes of pregnancy that it was once believed to be. References: 1. Evers IM, de Valk HW, Visser GHA. Risk of complications of pregnancy in woman with type 1 diabetes mellitus: nationwide prospective study in the Netherlands. BMJ 2004;328:915-18. 2. Holmes GKT. Screening for coeliac disease in type 1 diabetes. (Review: 63 references) Arch Dis Child 2002;87(6):495-9. 3. Arato A, Korner A, Veres G, Dezsofi A, Ujpál I, Madácsy L. Frequency of coeliac disease in Hungarian children with type 1 diabetes mellitus. Eur J Paediatr 2003;162:1-5. 4. Ashabani A, Abushofa U, Abusrewill S, Abdelazez M, Tucková L, Tlaskalová-Hogenová H. The prevalence of coeliac disease in Libyan children with type 1 diabetes mellitus. Diabetes Metab Rev 2003;19:69-75. 5. Eliakim R, Sherer DM. Celiac disease: fertility and pregnancy. Gynecol Obstet Invest 2001; 51:3-7. 6. Greco L, Veneziano A, Di Donato L, Zampella C, Pecoraro M, Paladine D, et al. Undiagnosed coeliac disease does not appear to be associated with unfavourable outcome of pregnancy. Gut 2004;53:149-151. Competing interests: None declared