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MarjaVääräsmäki

Gestational Diabetes Mellitus (Gdm)

Essentials

Pathogenesis and prevalence

  • Gestational diabetes mellitus (GDM) is abnormal glucose metabolism detected for the first time during pregnancy.
  • The development of GDM is facilitated
    • by insulin resistance increasing towards the end of pregnancy
      • This explains 80% of the cases.
      • Insulin resistance increases with an increasing amount of fat in the body.
    • by insufficient insulin secretion by pancreatic beta cells.
  • GDM usually occurs in the 1st pregnancy, already.
  • The prevalence of both obesity (BMI HASH(0x2f82cc8) 30 kg/m2 ) and GDM has increased in pregnant women.
    • According to a systematic review and meta-analysis published in 2021, the global prevalence of GDM was 14.7%, with substantial worldwide variation http://www.diabetesresearchclinicalpractice.com/article/S0168-8227(20)30899-8/fulltext. The study applied the IADPSG criteria.
    • Concerning obesity, see also Overweight in Pregnancy.
    • In Finland in 2021, the average BMI of pregnant women was 25.7 kg/m2 and more than 18% were obese; in 2010 the respective figures were 24 kg/m2 and 12%. Glucose tolerance test was abnormal in 21% in 2018 and in 11% in 2010.

Diagnosis

  • Screening can be done by performing a 2-hour 75-g glucose tolerance test.
    • HbA1c is not sufficiently sensitive and should not be used as a diagnostic method.
  • A glucose tolerance test should primarily be performed in week 24-28 of pregnancy.
  • A glucose tolerance test is unnecessary in the following cases:
    • a primigravida aged below 25, BMI below 25 kg/m2 and no type 2 diabetes in close relatives
    • a multigravida aged below 40 with BMI below 25 kg/m2 , who has not given birth to a macrosomic baby.
  • A glucose tolerance test should be done in week 12-16 of pregnancy in women:
    • with GDM in a previous pregnancy
    • with a BMI HASH(0x2f82cc8) 30 kg/m2 before pregnancy
    • with glucosuria in early pregnancy
    • with type 2 diabetes in close relatives (parents, siblings or children)
    • taking oral glucocorticoids.
  • If a glucose tolerance test done in early pregnancy is normal, it should always be repeated in week 24-28 of pregnancy.
  • Diagnosis is made if the glucose tolerance test shows one or more pathological concentrations (see table T1).
    • Notice that some national variation exists concerning what is considered normal in glucose tolerance test. Table T1 indicates the threshold concentrations recommended by the International Association of the Diabetes and Pregnancy Study Groups (IADPSG) in 2010 and concentrations used currently in Finland. Further national variation may apply.
2-hour 75-g glucose tolerance test
Abnormal concentrations (mmol/l; venous sample)
0 h1 h2 h
IADPSG 2010 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2827530/pdf/zdc676.pdfHASH(0x2f82cc8) 5.1HASH(0x2f82cc8) 10.0HASH(0x2f82cc8) 8.5
FinlandHASH(0x2f82cc8) 5.3HASH(0x2f82cc8) 10.0HASH(0x2f82cc8) 8.6
  • If the fasting concentration exceeds 7 mmol/l, the test should not be continued but the mother should be referred to a maternity outpatient clinic for assessment.
  • If more than one abnormal concentration is obtained in the test, GDM is usually more severe; in one in three of such mothers, medication must be started in addition to dietary treatment.

Differential diagnosis

  • Previously undiagnosed diabetes existing prior to pregnancy (type 1 or 2 diabetes, LADA or MODY) may also be diagnosed during pregnancy Diabetes: Definition, Differential Diagnosis and Classification.
  • If diabetes other than gestational diabetes is suspected in early pregnancy, HbA1c can be measured in addition to performing a glucose tolerance test, and the woman can be referred for assessment in specialized care.

Treatment

Self-monitoring

  • Nutritional guidance can be given and self-monitoring of blood glucose taught at a mother and child welfare clinic.
  • Target concentration for home monitoring
    • Fasting concentration< 5.5 mmol/l
    • Postprandial concentration 1 hour after a meal < 7.8 mmol/l
  • Blood glucose concentrations should be monitored before meals and 1 h postprandially on at least 2 days a week.
  • Self-monitoring will help to:
    • see the effects of diet and physical exercise on blood glucose concentrations
    • find the patients with gestational diabetes needing medication.

Nutritional therapy Interventions for Preventing Excessive Weight Gain during Pregnancy, Diet and/or Exercise for Pregnant Women for Preventing Gestational Diabetes Mellitus, Lifestyle Interventions for the Treatment of Women with Gestational Diabetes, Energy and Protein Intake in Pregnancy, Probiotics for Preventing Gestational Diabetes

  • Nutritional therapyhttp://www.dynamed.com/condition/gestational-diabetes-mellitus-gdm#DIET aims at reducing large blood glucose variation and at decreasing the occurrence of high blood glucose concentrations and lowering the peak concentrations.
  • Regular, relatively frequent small meals should be preferred, and rapidly absorbed carbohydrates should be avoided.
  • The recommended weight increase in overweight expecting mothers is 7-8 kg (1 600-1 800 kcal/day).
  • Moderate exercise is safe and to be recommended even during pregnancy.

Pharmacotherapy Treatments for Gestational Diabetes, Insulin Versus Oral Anti-Diabetic Pharmacological Therapies for Gestational Diabetes, Metformin for Gestational Diabetes

Follow-up of pregnancy and childbirth

  • If nutritional therapy is sufficient and the pregnancy is otherwise unproblematic, the risk of perinatal complications is low and the pregnancy can be followed up at a maternal welfare clinic.
  • If the blood glucose target concentrations are exceeded during nutritional therapy, medication should be started and follow-up carried out in specialized care.
  • There are no clear recommendations on the frequency of follow-up visits, but visits are recommended every 2-4 weeks with frequency increasing towards the end of pregnancy and with particular attention paid to foetal macrosomia, blood glucose control and blood pressure problems.
  • It is important to monitor the growth of the uterus and the development of foetal weight in order to be able to detect foetal macrosomia early enough and to be able to plan the time and mode of delivery at the maternity hospital Gestational Diabetes Mellitus and Pregnancy Outcomes.
  • The definition of macrosomia varies. In many European countries and the USA, the upper limit of normal birthweight in full-term babies is considered to be at 4 000 g, and a neonate weighing more than that is considered macrosomic. Large for gestational age (LGA) is defined as birthweight being greater than the 90th percentile at birth and takes into account the child´s gestational age. In Finland, a neonate is considered macrosomic when birthweight is more than 2 standard deviation (SD) over the average birthweight in the reference population (for a full-term baby 4 500 - 4 600 g).
    • Macrosomia is about twice as common in foetuses of patients with gestational diabetes receiving insulin treatment than in those receiving dietary treatment.
    • There are no similar comparisons for metformin-treated patients. Metformin-treated patients have a smaller incidence of macrosomia compared to insulin-treated gestational diabetes patients.
    • Risk factors for macrosomia include the severity gestational diabetes, maternal obesity, large weight gain during pregnancy, dyslipidaemia (low HDL and high triglyceride concentration) and a history of having had a macrosomic baby Gestational Diabetes Mellitus and Pregnancy Outcomes.
    • Maternal hyperglycaemia causes foetal hyperinsulinaemia, which has an anabolic effect. In this case, the risk of foetal oxygen deficiency during late pregnancy is increased.
  • In the foetus of a diabetic mother, the trunk circumference is large compared to the head circumference. In vaginal birth, this increases the risk of shoulder dystocia and brachial plexus injury, of other problems with assisted delivery and of maternal tears.
  • The risk of gestational hypertension and pre-eclampsia is increased in people with gestational diabetes and is about 2 times higher than in the general population. The risk is higher in insulin-treated than in diet-treated patients Gestational Diabetes Mellitus and Pregnancy Outcomes Elevated Blood Pressure in Pregnancy (Gestational Hypertension, Pre-Eclampsia).
  • With lifestyle treatment, pregnancy can usually be allowed to continue for 7-12 days beyond the calculated delivery date if the glucose control is good and there are no other complications associated with the pregnancy.
  • In the case of pharmacological therapy, the induction of labour is considered after the completion of week 39 of pregnancy, but at the latest around the calculated delivery date, because of the increased risk of asphyxia in late pregnancy.
  • Delivery is recommended after week 38 of pregnancy if
    • the foetus is becoming macrosomic (weight estimate +2 SD)
    • the mother's glucose homeostasis is not optimal or
    • there are other risk factors associated with the pregnancy.
  • Delivery according to individual assessment:
    • Usually vaginally if the child is estimated to weigh below 4 000 g
    • Usually by caesarean section if the child is estimated to weigh over 4 500 g
    • National differences may apply.
  • The accumulation of risk factors related to the mother (obesity, duration and severity of hyperglycaemia) and the foetus (macrosomia) increases neonatal problems in gestational diabetes.
    • Hypoglycaemia is the most common neonatal problem.
      • About 30% of neonates of mothers with gestational diabetes have plasma glucose concentrations of < 2.6 mmol/l and 20% < 2.0 mmol/l in the first days.
    • The child has an approximately 1.5-fold risk of RDS (respiratory distress syndrome) or TTN (transient tachypnoea of the newborn).
    • Other neonatal findings include polycythaemia, hyperbilirubinaemia, hypocalcaemia and myocardial thickening.
    • Neonates are 2-4 times more likely to be admitted to the neonatal intensive care unit.

Further maternal follow-up Gestational Diabetes Mellitus and Future Risk of Diabetes, Abnormal Screening Glucose Challenge Test in Pregnancy and Future Risk of Diabetes, Prevention of Type 2 Diabetes in Persons at Increased Risk for the Development of T2d, Diet and/or Exercise for Pregnant Women for Preventing Gestational Diabetes Mellitus, Prevention of Type 2 Diabetes by Life-Style Changes

  • Postnatal glucose tolerance test (reference concentrations: fasting concentration< 6.1 mmol/l and 2-hour concentration< 7.8 mmol/l)
    • For patients on medication, after 6-12 weeks
    • For patients on dietary treatment, after about 1 year
      • In this connection, BMI and blood pressure should be checked and the patient motivated to achieve/maintain normal weight and a healthy, physically active lifestyle.
    • Subsequently every 1-3 years (depending on the results and the maternal risks)
      • Glucose tolerance test or HbA1c, BMI, waist circumference, blood pressure, plasma lipids
    • Gestational diabetes recurs in about 40-60% of the patients. The risk is increased by:
      • early GDM (before week 24) in the preceding pregnancy
      • history of pharmacological treatment
      • born macrosomic baby
      • maternal overweight or large weight gain between pregnancies
      • multiparity.
    • The risk of developing diabetes (particularly type 2 diabetes) is significantly increased Gestational Diabetes Mellitus and Future Risk of Diabetes.
      • It is 10-fold over 10 years compared to those who had a pregnancy without developing gestational diabetes.
    • The risk of diabetes (type 2 diabetes) is increased by:
      • HASH(0x2f82cc8) 2 abnormal concentrations in a glucose tolerance test during pregnancy
      • need for pharmacological therapy during pregnancy
      • age over 35 years
      • further pregnancies after gestational diabetes
      • abnormal concentration in a postnatal glucose tolerance test
      • overweight.
    • The subsequent risk of type 1 diabetes is about 5% (in insulin-treated patients 5-10%).
    • The risk of developing type 2 diabetes can be reduced by achieving (or maintaining) normal weight, exercising and healthy eating Prevention of Type 2 Diabetes in Persons at Increased Risk for the Development of T2d.
    • Gestational diabetes, particularly if associated with maternal overweight, increases the risk of subsequent obesity, disturbances of glucose metabolism and the metabolic syndrome in the child. There may also be an increased risk of cardiovascular diseases.

References

  • Crowther CA, Samuel D, McCowan LME, et al. Lower versus Higher Glycemic Criteria for Diagnosis of Gestational Diabetes. N Engl J Med 2022;387(7):587-598. [PubMed]
  • Hillier TA, Pedula KL, Ogasawara KK, et al. A Pragmatic, Randomized Clinical Trial of Gestational Diabetes Screening. N Engl J Med 2021;384(10):895-904. [PubMed]
  • Vounzoulaki E, Khunti K, Abner SC, et al. Progression to type 2 diabetes in women with a known history of gestational diabetes: systematic review and meta-analysis. BMJ 2020;369():m1361. [PubMed]
  • van Kempen AAMW, Eskes PF, Nuytemans DHGM, et al. Lower versus Traditional Treatment Threshold for Neonatal Hypoglycemia. N Engl J Med 2020;382(6):534-544. [PubMed]

Evidence Summaries