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2.1
Diabetes in Pregnancy
Pregnancy in Diabete

Diabetes in pregnancy develops when the pancreas do not produce sufficient insulin in the setting of hyperglycemia induced by this physiological event. Despite its incompletely understood etiology, early recognition is mandatory in order to reduce the risk of many maternal and fetal complications. Repeated measurements of serum glucose levels are needed to make the diagnosis.

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WIKIDATA, CC BY 2.0

Presentation

Under physiological circumstances, placental hormones, increased maternal adiposity, increased pancreatic secretion of insulin, as well as several other factors, together induce a state of insulin resistance in the mother midway through pregnancy [1] [2]. Due to still unknown reasons, some women progress to a state of permanent insulin resistance and develop diabetes in pregnancy.This is described as glucose intolerance that was either unrecognized or absent before pregnancy (the terms pre-gestational diabetes, or overt diabetes are used as well) [1] [2] [3]. Diabetes in pregnancy affects between 2-5% of all pregnant women, and various risk factors have been established: African American, Hispanic and Asian ethnicity (all predispose to a higher rate of diabetes mellitus type 2), preexisting hypertension, history of unexplained miscarriages and stillbirths, a positive family history for diabetes mellitus, obesity, older maternal age, polycystic ovarian syndrome (POS), macrosomia (birth weight of more than 4000 g) of babies born from previous pregnancies, and of course, prior history of diabetes in pregnancy [1] [4]. Although not always, the clinical presentation of increased glucose intolerance is practically absent, as the majority of women are asymptomatic [1]. However, numerous maternal and fetal complications are described in the absence of an early diagnosis and adequate therapy. Women who develop diabetes in pregnancy suffer from recurrent urinary tract infections (UTIs) and may develop hypertension, preeclampsia or eclampsia, a life-threatening disorder [1] [2] [4] [5]. Moreover, the risk of preterm labor is increased as a result of polyhydramnios that frequently develops [2] [4]. On the other hand, excessive fetal growth resulting in macrosomia is virtually always a complication of GDM, which predisposes fetuses to metabolic abnormalities and injuries during delivery (eg. shoulder dystocia and the frequent need for cesarean delivery), while neonatal metabolic changes (hyperbilirubinemia, hypoglycemia, and respiratory distress) are also common [4] [5]. In addition to short-term adverse events, diabetes mellitus can persist even after pregnancy, and a high incidence of cardiovascular diseases in mothers has been reported [1] [2] [4] [5].

Entire Body System

  • Weight Loss

    We also identified a trial that was designed to evaluate the effects of a weight loss and exercise intervention compared with lifestyle education also in obese women with a history of GDM planning a subsequent pregnancy, however it has not yet been published [doi.org]

    Often, women have no symptoms of diabetes (increased thirst, increased hunger, increased urination, weight loss or gain) and screening is the only way to identify high glucose levels. [livescience.com]

    Certain basic lifestyle changes may help prevent diabetes after gestational diabetes: Weight loss- losing weight can help avoid developing type 2 diabetes. A Healthy BMI is 20 – 25. [diabetes.ie]

    Symptoms of Type 1 may include increased thirst and urination, constant hunger, weight loss, blurred vision, and extreme fatigue. [americanpregnancy.org]

    […] organs Blood vessels Nerves Eyes Kidneys Daily insulin injections may help prevent these complications Three types of diabetes Insulin-dependent diabetes mellitus (IDDM) Type I or juvenile diabetes B cells don't produce insulin Classic presentation Weight [en.wikibooks.org]

  • Falling

    OBJECTIVE: To investigate the association of falling insulin requirements (FIR) among women with preexisting diabetes with adverse obstetric outcomes and maternal biomarkers longitudinally in pregnancy. [ncbi.nlm.nih.gov]

    Remember insulin requirements increase progressively from the 2nd trimester until the last month of gestation, when a slight fall-off may be noted Hypoglycemia and loss of awareness is common in early pregnancy. [diabetes.co.uk]

    For women with type 1 or type 2 diabetes, the best preparation for a healthy pregnancy starts with getting the right information and advice before you fall pregnant. Read more in our Pregnancy and diabetes factsheet. [ndss.com.au]

    The house can be messy, the laundry can fall behind and you can be less than perfect. You're helping your baby grow and be healthy, and that's your first priority. Get enough sleep. Ask for help in getting tasks done. [allinahealth.org]

    Diagnosis of gestational diabetes mellitus: falling through the net. Diabetologia Clinical and Experimental Diabetes Metabolism, 2015, 58(9):2003-12. Maruichi MD, Amadei G, Abel MNC. Diabetes mellitus gestacional. [acm.org.br]

Gastrointestinal

  • Vomiting

    […] dysplasia, cervix 654.6 early onset of delivery (spontaneous) 644.2 eclampsia, eclamptic (coma) (convulsions) (delirium) (nephritis) (uremia) 642.6 edema 646.1 effusion, amniotic fluid 658.1 embolism emesis (gravidarum) - see Pregnancy, complicated, vomiting [icd9data.com]

    You should use these if your blood glucose levels are high, or if you are vomiting or have diarrhoea. [nhs.uk]

    All women should test urine for ketones if blood glucose is high, if vomiting occurs or if they are unwell. [diabetes.co.uk]

    […] small, healthy, non-sugary meal an hour or so before undergoing the test. during the hour between having the drink and giving the blood sample you walk around so that your body is assisted to metabolize the sugar you have drunk. you have not been ill or vomiting [mamamaternity.co.nz]

  • Polydipsia

    Symptoms include excessive excretion of urine (polyuria), thirst (polydipsia), constant hunger, weight loss, vision changes, and fatigue. These symptoms may occur suddenly. [who.int]

    Children with type 1 diabetes typically present with the hallmark symptoms of polyuria/polydipsia, and approximately one-third present with DKA ( 3 ). [doi.org]

  • Increased Appetite

    appetite Increased thirst Excessive urination Severe cases can cause ketoacidosis Non-insulin dependent diabetes mellitus (NIDDM) Type II diabetes Classically seen in adults who are overweight Insulin is present but insulin receptors unresponsive Gestational [en.wikibooks.org]

    Pregnancy hormones decrease fasting glucose levels, increase fat deposition, delay gastric emptying and increase appetite. However, over the course of pregnancy, postprandial glucose concentrations increase as insulin resistance increases. [patient.info]

Cardiovascular

  • Heart Disease

    We have no information on the exact diagnosis; however, heart disease recorded at the time of the birth would have been due to congenital defect, rheumatic heart disease or cardiomyopathy. [doi.org]

    The condition is often complicated by other risk factors such as obesity and heart disease. [crcpress.com]

    Pregnancy stresses your heart, and diabetes raises the risk for heart disease. If you have risk factors for heart disease, your doctor may want you to have a screening test for blocked arteries of the heart. [hormone.org]

    A pre-pregnancy exam by your doctor includes: measuring your A1C level to make sure blood glucose levels are under control as well as an assessment of any complications, such as high blood pressure, heart disease, and kidney, nerve, and eye damage. [womenshealthassociates.org]

    Class H - diabetic women with coronary artery or other heart disease. It is very important for a mother to closely manage her diabetes during pregnancy. [chop.edu]

Eyes

  • Background Retinopathy

    Soubrane G, Canivet J, Coscas G (1985) Influence of pregnancy on the evolution of background retinopathy. Preliminary results of a prospective fluorescein angiography study. [link.springer.com]

Fetus

  • Increased Birth Weight

    There is no agreement on the glycaemic threshold for these adverse outcomes - indeed, large studies have indicated a strong, continuous association of maternal glucose levels (below those diagnostic of diabetes) with increased birth weight, and significant [patient.info]

    There were strong associations with birth weight above the 90th percentile that increased across the increasing glycemia categories. [content.nejm.org]

Neurologic

  • Seizure

    Main outcome measures Primary perinatal outcomes were gestational age, birth weight, Apgar score at five minutes, admission to a neonatal intensive care unit, need for postpartum antibiotics, and seizures. [doi.org]

    As repeated EEG still showed presence of seizure activity; the baby was started on diphenylhydantoin (Dilatin®). Brain MRI, HUS, BAER test and ophthalmology exams were all normal. [nature.com]

    If left untreated it can lead to eclampsia which is a condition in which one or more seizures occur in a pregnant woman suffering from high blood pressure, often followed by coma and posing a threat to the health of mother and baby. [diabetesdaily.com]

    It might lead to the baby being born early and also could cause seizures or a stroke (a blood clot or a bleed in the brain that can lead to brain damage) in the woman during labor and delivery. [cdc.gov]

    Unmonitored and uncorrected hypoglycemia can lead to neonatal seizures, brain damage, and death. The strongest predictor of neonatal hypoglycemia is maternal mean blood glucose level during labor. [emedicine.medscape.com]

  • Convulsions

    […] cervicitis (conditions classifiable to 616.0 ) 646.6 chloasma (gravidarum) 646.8 cholelithiasis 646.8 cholestasis 646.7 chorea (gravidarum) - see Eclampsia, pregnancy coagulation defect 649.3 conjoined twins 678.1 contraction, pelvis (general) 653.1 convulsions [icd9data.com]

    Hypoglycemia is generally considered to be without risk for the fetus, as demonstrated in women with pre-existing diabetes (79,92–94), as long as it is not sustained and maternal loss of consciousness, convulsion, and fall or trauma is avoided during [guidelines.diabetes.ca]

Urogenital

  • Polyuria

    Polyuria. Polyuria is an increase in urination. While most pregnant women undergo this symptom, early in the pregnancy before baby has a chance to put pressure on the bladder, it could be a sign of gestational diabetes. [babymed.com]

    Symptoms include excessive excretion of urine (polyuria), thirst (polydipsia), constant hunger, weight loss, vision changes, and fatigue. These symptoms may occur suddenly. [who.int]

    At 34 + 0 weeks of gestational age, polyuria and unexpected weight loss (2 kg/week) with hyperglycemia occurred, and total dose of daily insulin requirement was increased up to 50 IU/day. [ekjm.org]

    The believe that it might represent true diabetes was based on the fact that many women that presented glycosuria had typical symptoms of diabetes such as polydpsia, polyuria, polyhydramnios and even adverse fetal outcomes [ 8 ]. [dmsjournal.biomedcentral.com]

    Children with type 1 diabetes typically present with the hallmark symptoms of polyuria/polydipsia, and approximately one-third present with DKA ( 3 ). [doi.org]

  • Kidney Failure

    Diabetes is a major cause of blindness, kidney failure, heart attacks, stroke and lower limb amputation. In 2016, an estimated 1.6 million deaths were directly caused by diabetes. [who.int]

    Diabetes can contribute to eye disorders and blindness, heart disease, stroke, kidney failure, amputation, and nerve damage. During pregnancy, the placenta supplies a growing fetus with nutrients and water. [chop.edu]

    Diabetes can contribute to eye disorders and blindness, heart disease, stroke, kidney failure, amputation, and nerve damage. What happens with diabetes and pregnancy? During pregnancy, the placenta supplies a growing fetus with nutrients and water. [stanfordchildrens.org]

    This can cause serious health problems, like heart disease, kidney failure and blindness. High blood sugar can be harmful to your baby during the first few weeks of pregnancy when his brain, heart, kidneys and lungs begin to form. [marchofdimes.org]

  • Renal Insufficiency

    Conversely, patients with diabetic nephropathy with renal insufficiency are at significant risk of GFR decline [ 88 ] and renal failure during and after pregnancy (60, see Table 11.19). [link.springer.com]

    Glibenclamide is contraindicated in cases of renal and hepatic insufficiency ( www.medsafe.govt.nz ). [doi.org]

Workup

Signs and symptoms of diabetes in pregnancy may not be apparent until delivery or until severe complications occur. For this reason, a thorough patient history is a vital step in assessing risk factors, after which screening methods should be implemented. The debate regarding screening protocols for diabetes in pregnancy is ongoing, with many authors suggesting that apart from low-risk individuals (Caucasian women under 25 years of age, a low body mass index - BMI, and no previous signs of glucose intolerance), serum glucose levels must be evaluated in all pregnant women [1] [2] [3] [4] [6] [7]. Numerous screening guidelines exist for diabetes in pregnancy, including those created by the National Diabetes Data Group (NDDG), American Diabetes Association (ADA), International Association of Diabetes and Pregnancy Study Groups (IADPSG), American College of Obstetricians and Gynecologists and several other [3] [5] [6]. However, the criteria formulated by the World Health Organization (WHO), updated in 2013, are most widely accepted. They recommend screening of all pregnant women by conducting an oral glucose tolerance test (OGTT) with 75g of glucose and subsequent serum measurements [3]. If fasting glucose levels are > 5.1 mmol/L or if levels after 1 hour are > 10 mmol/L, or if levels after 2 hours are > 8.5 mmol/L, a diagnosis of diabetes in pregnancy can be made [3]. Serum evaluation of hemoglobin A1c (HbA1C) is also proposed as a diagnostic tool for confirming diabetes in pregnancy, and the cut-off value of ≥48 mmol/mol (6.5%) was accepted as a supportive criterion for this condition [6].

Urine

  • Glycosuria

    Glycosuria was also found to be recurrent in successive pregnancies [ 11 ]. [dmsjournal.biomedcentral.com]

    False-negative test stick measurements can appear in patients with low glycosuria. The rate of glycosuria shows high individual differences and dependent on the concentration of vitamin C. [doi.org]

    For fasting glucose target, all used a value 50%, one (6%) >30%, and one (6%) >20% of the values higher than the target value; one (6%) used the appearance of glycosuria. [ncbi.nlm.nih.gov]

    Glycosuria of 2+ or above on one occasion or of 1+ or above on two or more occasions detected by reagent strip testing during routine antenatal care may indicate undiagnosed GDM. Consider further testing to exclude GDM. [patient.info]

Serum

  • Hypertriglyceridemia

    Pregnancy associated hypertriglyceridemia in normal and diabetic women: differences in insulin-dependent, non-insulin dependent and gestational diabetes. Diabetes. 1982;31:1092–7. [degruyter.com]

    This may help to recognize patients with higher risk of hypertriglyceridemia (those with poorly controlled DM and albuminuria) [ 107 ]. [link.springer.com]

Treatment

The optimum treatment for HNF1A/HNF4A maturity-onset diabetes of the young and ATP-sensitive potassium (K ATP ) channel neonatal diabetes, outside pregnancy, is sulfonylureas, but there is little evidence regarding the most appropriate treatment during [ncbi.nlm.nih.gov]

Any specific treatment versus routine antenatal care (subgroups by type of specific treatment) Comparison 2. [doi.org]

Management [ 5, 12 ] Treatment of GDM and good glycaemic control reduce serious perinatal morbidity and may also improve the woman's health-related quality of life [ 13, 14 ]. It is often controversial as to when GDM requires treatment. [patient.info]

Prognosis

Gestational diabetes: problems in classification and implications for long-range prognosis. Adv. Exp. Med. Biol. 1985;189:47-63. http://doi.org/bsds. [ Links ] 30. American College of Obstetricians and Gynecologists. [scielo.org.co]

HbA1c for diagnosis and prognosis of gestational diabetes mellitus. Diabetes Res Clin Pract. 2015;110:38-43. https://doi.org/10.1016/j.diabres.2015.07.014 Khalafallah A, Phuah E, Al-Barazan A, Nikakis I, Redford A, Clarkson W. et al. [revista.fecolsog.org]

Prognosis The perinatal risks to mother and baby are similar to those with known diabetes, mainly relating to the problems of a large baby. Treatment of GDM is effective in reducing macrosomia, pre-eclampsia and shoulder dystocia [ 19 ]. [patient.info]

Follow-up and prognosis Gestational diabetes resolves postpartum in more than 90% of women. In general, all insulin and oral hypoglycaemic drugs are ceased immediately postpartum with ongoing blood glucose monitoring until discharge from hospital. [nps.org.au]

Etiology

The genetic etiology of gestational diabetes mellitus has largely been found to overlap that of T2D. [ncbi.nlm.nih.gov]

The clinical role of maternal hyperglycemia below the threshold for the diagnosis of gestational diabetes (GDM) in the etiology of macrosomia remains an area of controversy. [doi.org]

Despite its incompletely understood etiology, early recognition is mandatory in order to reduce the risk of many maternal and fetal complications. Repeated measurements of serum glucose levels are needed to make the diagnosis. [symptoma.com]

Etiology Mutations in the PHOX2B gene are found in a significant number of patients with Haddad syndrome. The documents contained in this web site are presented for information purposes only. [orpha.net]

Epidemiology

Asthma/metabolism Bronchopulmonary Dysplasia/epidemiology Bronchopulmonary Dysplasia/metabolism Child Diabetes, Gestational/epidemiology* Diabetes, Gestational/metabolism Disease Models, Animal Female Hernias, Diaphragmatic, Congenital/epidemiology Hernias [ncbi.nlm.nih.gov]

Mitchell, Descriptive Epidemiology of Non‐syndromic Complete Atrioventricular Canal Defects, Paediatric and Perinatal Epidemiology, 26, 6, (515-524), (2012). ZHIXIAN SUI, ROSALIE M. GRIVELL and JODIE M. [doi.org]

Pathophysiology

Barriers were poor socioeconomic status, lack of family, peer and community support, effects of pregnancy, complicated therapeutic regimen, pathophysiology of diabetes, cultural and religious beliefs, and poor health care system. [ncbi.nlm.nih.gov]

Having fetal hyperinsulinism is a risk factor for development of both obesity and abnormal glucose metabolism, and might be implicated in pathophysiology. [doi.org]

Prevention

Prevention You can lower your chance of getting gestational diabetes by losing extra weight before you get pregnant if you are overweight. Being physically active before and during pregnancy also may help prevent gestational diabetes. [niddk.nih.gov]

Prevention Simple lifestyle measures have been shown to be effective in preventing or delaying the onset of type 2 diabetes. [who.int]

If you also limit sweets and fats, you may prevent your prediabetes from becoming a problem for your developing baby’s health. [livestrong.com]

References

  1. Gilmartin A “Bird” H, Ural SH, Repke JT. Gestational Diabetes Mellitus. Rev Obstet Gynecol. 2008;1(3):129-134.
  2. Buchanan TA, Xiang AH. Gestational diabetes mellitus. J Clin Invest. 2005;115(3):485-491.
  3. Agarwal MM. Gestational diabetes mellitus: An update on the current international diagnostic criteria. World J Diabetes. 2015;6(6):782-791.
  4. Alfadhli EM. Gestational diabetes mellitus. Saudi Medical Journal. 2015;36(4):399-406.
  5. Rani PR, Begum J. Screening and Diagnosis of Gestational Diabetes Mellitus, Where Do We Stand. J Clin Diagn Res. 2016;10(4):QE01-QE04.
  6. Renz PB, Cavagnolli G, Weinert LS, Silveiro SP, Camargo JL. HbA1c Test as a Tool in the Diagnosis of Gestational Diabetes Mellitus. Wagner B, ed. PLoS ONE. 2015;10(8):e0135989.
  7. Karagiannis T, Bekiari E, Manolopoulos K, Paletas K, Tsapas A. Gestational diabetes mellitus: why screen and how to diagnose. Hippokratia. 2010;14(3):151-154.
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