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This gene causes about 70 per cent of cases of MODY. It causes diabetes by lowering the amount of insulin made by the pancreas. People who have inherited a change in this gene are likely to have had a birth weight of 9lb or more around 4kg. They may also have had a low blood sugar at, or soon after, birth which might have needed treatment.

People with HNF4-alpha are generally treated with a sulphonylurea tablet but may progress on to needing insulin. People with this type of MODY can have a variety of problems including renal cysts cysts of the kidneys , uterine abnormalities and gout, as well as diabetes. Often the renal cysts can be detected in the womb before a baby is born.

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Recent observational data demonstrated the feasibility and good uptake of the 2-step approach Since there is no clear glucose threshold above which pregnancy outcomes responsive to glycemic management occur ,, , controversy persists as to the best diagnostic thresholds to define GDM. However, since this publication, national organizations have published guidelines that are divergent in their approach to screening and diagnosis of GDM — , thus perpetuating the international lack of consensus on the criteria for diagnosis of GDM.

However, it was recognized that the IADPSG 1-step strategy has the potential to identify a subset of women who would not otherwise be identified as having GDM and could potentially benefit with regards to certain perinatal outcomes. As outlined in the CPG, those who believe that all cases of hyperglycemia in pregnancy need to be diagnosed and treated i.

LGA rate and birth weight progressively increased with more dysglycemia and were increased in both groups. However, in this study, only women who were positive by HAPO 2.

Differentiation of Diabetes by Pathophysiology, Natural History, and Prognosis

Since the publication of the IADPSG consensus thresholds, there have been numerous retrospective studies that have examined the impact of adoption of these criteria. It is difficult to apply the results of these studies to clinical practice due to their retrospective nature and the wide variation in the comparison groups used. In all of these studies, adoption of IADPSG criteria has led to an increase in the number of cases diagnosed while the impact on perinatal outcomes is inconsistent — However, others did not find reductions in LGA ,,, , and 1 study found an increase in primary caesarean section rate Given this lack of evidence, it is possible that the decision regarding the recommended screening method will be determined by the economic implications on health-care resources.

Decision analysis modelling studies done in other countries ,— have yielded a variety of results and many are of questionable applicability in the Canadian setting because of differing cost and screening and diagnostic strategies. A small observational study from Ireland suggested that maternal BMI may be an important consideration in choice of which diagnostic thresholds to use Further higher-quality evidence would be helpful in establishing if maternal BMI and other clinical risk factors should guide which diagnostic thresholds are used. Most cost analysis evaluations support a sequential screening approach to GDM.

Therefore, adequately powered prospective studies to compare these 2 approaches are needed.

1. Introduction

Since pregnancy may be the first time in their lives that women undergo glucose screening, monogenic diabetes may be picked up for the first time in pregnancy. Monogenic diabetes first diagnosed in pregnancy should be suspected in the women with GDM who lack risk factors for GDM and type 1 diabetes and have no autoantibodies see Definition, Classification, and Diagnosis of Diabetes, Prediabetes and Metabolic Syndrome chapter, p.

Pathophysiology and Therapy

A detailed family history can be very helpful in determining the likely type of monogenic diabetes. This is important because the type of monogenic diabetes influences fetal risks and management considerations.

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During pregnancy, the usual phenotype for MODY 2 of isolated elevated FBG is not always seen, even though this phenotype may be present outside of pregnancy in the same woman The best way to manage women with GCK mutation during pregnancy has yet to be established, but regular fetal growth assessment can aid in the establishment of appropriate glucose targets during pregnancy for women with documented or strongly suspected GCK mutations. These forms of monogenetic diabetes have greater increased risk of macrosomia and neonatal hypoglycemia that may be prolonged especially in neonates that have MODY 1 HNF4 alpha mutation.

Although women with these later forms of monogenic diabetes are usually exquisitely sensitive to sulfonylureas, they should be transitioned to insulin as they prepare for pregnancy or switched to insulin during pregnancy, if this has not occurred preconception, for the same reasons as avoiding glyburide use in women with GDM. Weight gain. The IOM guidelines for weight gain during pregnancy were developed for a healthy population and little is known regarding optimal weight gain in women with GDM.

Retrospective cohort studies of GDM pregnancies show that only Those gaining more than the IOM recommendations had an increased risk of preeclampsia , caesarean deliveries , , macrosomia , , LGA — and GDM requiring pharmacological agents Modification of IOM criteria, including more restrictive targets of weight gain, did not improve perinatal outcomes of interest These researchers suggest that, in contrast to obesity and GDM prevention, preventing excessive GWG may be a more viable option as women are closely followed in pregnancy.

A large number of women with overweight or obesity and with GDM gain excessive weight in pregnancy , and a large proportion exceed their IOM total target by the time of GDM diagnosis A systematic review found that pregnant women with overweight or obesity who gain below the IOM recommendation, but have an appropriately growing fetus, do not have an increased risk of having a SGA infant , leading some to recommend that encouraging increased weight gain to conform with IOM guidelines will not improve maternal or fetal outcomes A Cochrane review 49 trials of 11, women was performed to evaluate the effectiveness of diet or exercise or both in preventing excessive gestational weight gain and associated adverse pregnancy outcomes Study interventions involved mainly diet only, exercise only and combined diet and exercise interventions compared with standard care.

Low glycemic load GL diets, supervised or unsupervised exercise only or diet and exercise in combination all led to similar reductions in the number of women gaining excessive weight in pregnancy. There was no clear difference between intervention and control groups with regards to preeclampsia, caesarean section, preterm birth and macrosomia. Further studies are needed to develop weight gain guidelines for GDM patients and to determine whether weight gain less than the IOM guidelines or weight loss in pregnancy is safe.

Until this data are available, women with GDM should be encouraged to gain weight as per the IOM guidelines for the BMI category to reduce adverse maternal and neonatal outcomes and postpartum weight retention. Nutrition therapy. Nutrition therapy is a cornerstone for managing GDM. All women at risk for or diagnosed with GDM should be assessed, counselled and followed up by a registered dietitian when possible — Nutrition therapy should be designed to promote adequate nutritional intake without ketosis, achievement of glycemic goals, appropriate fetal growth and maternal weight gain — Recommendations for nutrition best practice and a review of the role of nutrition therapy in GDM management is available.

A great variety of diets are used for managing GDM. While carbohydrate moderation is usually recommended as first-line strategy to achieve euglycemia , evidence available to support the use of a low-glycemic-index GI diet is increasing. A randomized controlled trial of 70 healthy pregnant women, randomized to low glycemic index GI vs.

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  • An earlier systematic review of 9 randomized controlled trials, in which 11 different diet types were assessed within 6 different diet comparisons, did not support the recommendation of 1 diet type over another as no significant differences were noted in macrosomia, LGA or caesarean section rates However, a more recent systematic review and meta-analysis does support the use of low GI diets Only the low-GI diet was associated with less frequent insulin use and lower newborn weight without an increase in numbers of SGA and macrosomia Results of a meta-analysis of 5 randomized controlled trials and a systematic review in GDM patients showed that low-GI diets reduce the risk of macrosomia and LGA, respectively.

    Low-GI diets are associated with lower postprandial blood glucoses in recent randomized controlled trials , In summary, current evidence although limited, suggests that women with GDM may benefit from following a low-GI meal pattern Physical activity. In combination with nutritional intervention, physical activity appears to be more effective for GDM management than GDM prevention. No studies had an effect on infant birth weight or macrosomia rate and only 1 was successful in reducing GWG.

    It can be argued that these studies were not powered enough to demonstrate any impact on birthweight or on adverse pregnancy outcomes. Indeed, relevant limitations for these studies include the following: samples were small mean of 43 participants per study , participants had different metabolic profiles and risks factors, and different diagnostic criteria for GDM were used.

    The best type of intervention that should be recommended is unclear since all the successful programs used different exercise modalities in terms of intensity, type, duration and frequency.

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    More recently, an initiative in India, the Wings Project, demonstrated that an intervention based on increasing total footsteps with pedometers was able to improve glycemic control in women with GDM and reduce adverse neonatal outcomes in the more active tertiles when compared to their GDM counterparts in the upper tertiles of sedentary behaviour Since no exercise-related injuries were experienced during pregnancy in all those studies, physical activity intervention seems safe to recommend.

    All together, current knowledge suggests that physical activity interventions in women with GDM should be encouraged unless obstetrical contraindications exist as physical activity may be an important component of GDM management. However, identification of a specific program of physical activity that should be prescribed to GDM women is currently not possible. Further studies are needed involving larger populations to enable the prescription of an evidence-based physical activity intervention.

    Glycemic control. However, it should be noted that the mean FBG derived from the total of subjects in this report was 0. BG levels in pregnant women with obesity without diabetes were slightly higher than their lean counterparts in a study in which CGM was performed in early and late pregnancy after placing pregnant women with obesity or normal weight on a controlled diet Importantly, it has been demonstrated that the diagnostic OGTT values were not the best predictors of outcomes whereas CBG levels during treatment were strongly correlated to adverse pregnancy outcomes Even if BG can normally and physiologically decrease during pregnancy below the traditional level of 4.

    On the other hand, recent studies have questioned the upper limit of the FBG target. Risks of maternal hypoglycemia or fetal low birth weight were not evaluated in this review and adjustment for maternal BMI and different diagnostic criteria for GDM was not performed. Even if the frequency of SGA infants was lower across the tertile of mean maternal fasting glycemia in this study, SGA rate in women with the lowest mean FBG was not increased and was, in fact, comparable with the rate of the background population.

    SGA rate was inversely correlated with maternal weight gain before assessment, suggesting that SGA could be partly prevented by adequate follow up of GWG in those women. However, large, well-conducted and randomized controlled trials comparing different BG targets are needed to directly address optimal fasting and postprandial BG targets. Further studies should also assess the risk of maternal hypoglycemia, SGA, insulin use and cost-effectiveness of such modification. Despite reduced perinatal morbidity with interventions to achieve euglycemia in women with GDM, increased prevalence of macrosomia persists in this population.

    To improve outcomes, 4 randomized controlled trials — have examined the use of fetal abdominal circumference AC as measured sonographically and regularly in the third trimester to guide medical management of GDM.

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    Indeed, it may be difficult to apply this flexible approach given the extreme glycemic targets that were used, the fact that routine determination of AC is not done or sufficiently reliable, and frequent ultrasounds may not be accessible to most centres. Both fasting and postprandial testing are recommended to guide therapy in order to improve fetal outcomes 89, CGMS have been useful in determining previously undetected hyperglycemia, but it is not clear if it is cost effective — Women using CGM had less glucose variability, less BG values out of the target range, as well as less preeclampsia, primary caesarean section and lower infant birthweight.

    A1C was lower in the CGM group but not statistically significantly different.

    More studies are needed to assess the benefits of CGM in this population. Older studies raised the possibility that elevated ketoacids may be detrimental to the fetus 94, While the clinical significance of these findings are questionable, it appears prudent to avoid ketosis. Use of new technologies and web-based platforms for BG monitoring in pregnant women with diabetes in Canada and worldwide is rapidly increasing.

    These initiatives allow for 2-way communication with women monitoring and transmitting their BG results in real time to health-care providers for feedback. Studies have demonstrated Enhanced patient empowerment and greater satisfaction with the care received are also reported in groups using new monitoring technology —,,, However, generalizability of those studies is questionable as these studies were small, conducted in very specific settings and used different types of technologies and e-platforms.

    Furthermore, acceptance of these interventions by marginalized population subgroups and in remote regions would also be important to determine. Finally, studies assessing cost effectiveness of these measures, both direct health system resources utilization and indirect work absenteeism, parking, daycare fees are needed. Systematic reviews of the literature on the use of technology to support healthy behaviour interventions for healthy pregnant women and women with GDM , showed that good quality trials in this area are few and research on this topic is in its infancy stage.

    This is evidenced by the focus on intervention acceptance measures, use of small sample sizes, lack of demonstration of causality and lack of examination of long-term effects or follow up. In summary, new technologies and telehomecare programs have so far shown encouraging results to reduce medical visits and favour patient empowerment without increasing complication rates in pregnant women with diabetes.

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    In an era of increased prevalence of GDM, well designed and sufficiently powered randomized controlled trials are needed to evaluate the effectiveness of technology as a tool for glucose management, healthy behaviour interventions and a way of relieving health-care system burden. If women with GDM do not achieve BG targets within 2 weeks of initiation of nutritional therapy and exercise, pharmacological therapy should be initiated , The use of insulin to achieve glycemic targets has been shown to reduce fetal and maternal morbidity , A variety of protocols have been used, with multiple daily injections MDI being the most effective Insulin usually needs to be continuously adjusted to achieve glycemic targets.

    Although the rapid-acting bolus analogues aspart and lispro can help achieve postprandial targets without causing severe hypoglycemia — , improvements in fetal outcomes have not been demonstrated with the use of aspart or lispro compared to regular insulin , see Pre-Existing Diabetes Type 1 and Type 2 in Pregnancy: Pharmacological therapy. Glargine and detemir have primarily been assessed in women with pre-existing diabetes in pregnancy see Pre-Existing Diabetes Type 1 and Type 2 in Pregnancy: Pharmacological therapy.

    Randomized trial evidence suggests levemir is safe and may afford less maternal hypoglycemia compared to neutral protamine hagedorn NPH , while observational studies suggest that glargine, although theoretically less desirable, is also safe. In several meta-analyses of randomized trials studying the use of metformin compared with insulin in women with gestational diabetes, women treated with metformin had less weight gain and less pregnancy-induced hypertension compared to women treated with insulin — Infants of mothers using metformin had lower gestational age and less neonatal hypoglycemia.

    On the other hand, there was conflicting evidence regarding preterm birth, with some studies finding a significant increase with the use of metformin, while others did not. This finding was mainly demonstrated by the Metformin in Gestational diabetes MiG trial , where there was an increase in spontaneous preterm births rather than iatrogenic preterm births.

    The reason for this was unclear. While metformin appears to be a safe alternative to insulin therapy, it does cross the placenta. Results of The Offspring Follow Up of the Metformin in Gestational diabetes MiG TOFU trial, at 2 years, showed that the infants exposed to metformin have similar total fat mass but increased subcutaneous fat, suggesting a possible decrease in visceral fat compared to unexposed infants In another follow-up study of infants exposed to metformin during pregnancies with gestational diabetes, children exposed to metformin weighed more at the age of 12 months, and were heavier and taller at 18 months, however, body composition was similar as was motor, social and linguistic development.

    Studies looking at neurodevelopment showed similar outcomes between exposed and nonexposed infants at 2 years of age , In summary, long-term follow up from 18 months to 2 years indicate that metformin exposure in-utero does not seem to be harmful with regards to early motor, linguistic, social, , metabolic , and neurodevelopmental , outcomes.