By: Fatima Choudary

GESTATIONAL DIABETES

Gestational Diabetes • A condition in which pregnant women, who do not previously have Diabetes exhibit high blood sugar levels.• Usually occurs during the third trimester • It is caused when the insulin receptors do not function properly most likely due to pregnancy related hormones

Risk Factors• Previous diagnosis of gestational diabetes prediabetes, impaired glucose tolerance or impaired fasting glycaemia • Family history with a first degree relative with Type 2 Diabetes• Maternal age: a woman’s risk increases as her age increases (especially in women >35 years of age)• Previous pregnancy that resulted in a child with macrosomia • Ethnic background• Being overweight or obese • Studies show twice the risk in smokers vs. nonsmokers• About 40-60% of women with GDM have no Risk factor therefore it is beneficial to screen all pregnant women.

Symptoms• Usually there are no symptoms• And if any they are mild and not life threatening• May include:• Blurred vision• Fatigue • Increased thirst• Increased urination• Nausea • Vomiting•Weight loss despite increased appetite

Insulin• Is produced by the beta cells of the pancreas• It is produced in response to ATP from glucose metabolism closing Potassium channels and depolarizing the cell• Regulates carbohydrate and fat metabolism in the body • Promotes the entry of glucose into most cells (ex. Liver, skeletal muscle and fat)• In the liver the glucose is converted and stored as glycogen• In adipocytes it is stored as triglycerides • It is provided within the body in a constant proportion to remove the excess glucose from the blood, which would otherwise be toxic• It stops the use of fat as an energy source by inhibiting the release of glucagon from the alpha cells of the pancreas • It does not however cross the placenta

Insulin Regulation • Hyperglycemia, GH and Cortisol: Increase insulin secretion • Hypoglycemia and somatostatin: Decrease insulin secretion• Beta agonists (ex. Isoproterenol, terbutaline etc.): Stimulate Insulin secretion • Alpha agonists (ex. Phenylephrine, clonidine etc.): Inhibit Insulin secretion

Anabolic effects of Insulin• Increase glucose transport in skeletal muscle and adipose• Increase glycogen synthesis and storage• Increase triglyceride synthesis and storage • Increase sodium retention (in the kidneys)• Increase protein synthesis (in muscles)• Increase cellular uptake of potassium and amino acids • Inhibits ketoacidosis formation and lipolysis

Insulin deficiency • Type 1 Diabetes Mellitus: It is due to an autoimmune destruction of beta cells of the pancreas. Usually see islet leukocytic infiltration. Occurs in patients <30 years of age • Type 2 Diabetes Mellitus: It is due to Insulin resistance. Usually see Islet amyloid deposition. Occurs in patients >40 years of age• Diabetic Ketoacidosis: Which is a complication of Type 1 Diabetes Mellitus• Gestational Diabetes: Also a mechanism of insulin resistance

Pathophysiology• The mechanism underlying the etiology is unknown • The main cause is insulin resistance • Pregnancy hormones (such as: Progesterone, Cortisol, human placental lactogen, prolactin and estradiol) are thought to interfere with the action of Insulin as it binds to its insulin receptors• The interference probably occurs at the level of the cell signaling pathway• Insulin resistance is a normal phenomenon occurring in the second trimester of pregnancy, which can progress to levels seen in non pregnant type 2 diabetic patients • Placental hormones and increased fat deposit during pregnancy seem to mediate the insulin resistance

• Glucose travels across the placenta via diffusion facilitated by GLUT-3 carriers• In untreated gestational Diabetes the fetus is exposed to consistently high levels of glucose• This leads to increased fetal level of insulin • The growth stimulating effects of insulin can lead to excessive growth and large body (Macrosomia)• After birth the high levels of glucose disappears leaving the babies with ongoing increased insulin production leading to decreasing amounts of glucose eventually causing hypoglycemia

Diagnosis

• Fasting glucose test • 2 hour postprandial glucose test • Random glucose test • Screening glucose challenge test • Oral glucose tolerance test • Urinary glucose test

Diabetic diagnostic criteria

Condition 2 hour glucose Fasting glucose

HbA1c

mmol/l(mg/dl) mmol/l(mg/dl) %Normal <7.8 (<140) <6.1 (<110) <6.0

Impaired fasting glycaemia

<7.8 (<140) >6.1 (>110) & <7.0(<126)

6.0-6.4

Impaired glucose tolerance

>7.8 (>140) <7.0 (<126) 6.0-6.4

Diabetes mellitus

>11.1 (>200) >7.0 (>126) >6.5

Screening glucose challenge test • Aka O'Sullivan test is performed between 24-28 weeks • No previous fasting required • Involves drinking a solution containing 50 grams of glucose and measuring blood levels one hour later • If that comes back positive, you do a diagnostic test which involves measuring blood levels 3 hours after drinking a solution containing 50 grams of glucose.

Oral glucose tolerance test • Done in the morning after an overnight fast of 8-14 hours• During previous 3 days patient must have unrestricted diet (150g of carbohydrate and unlimited physical activity)• Involves drinking a solution containing a certain amount of glucose (75-100g) and drawing blood to measure glucose levels at the start and on set time intervals • The following values during the 100g of glucose OGTT are considered to be abnormal according to American Diabetes Association:• Fasting blood glucose level ≥95 mg/dl (5.33 mmol/L)• 1 hour blood glucose level ≥180 mg/dl (10 mmol/L)• 2 hour blood glucose level ≥155 mg/dl (8.6 mmol/L)• 3 hour blood glucose level ≥140 mg/dl (7.8 mmol/L)

Urinary Glucose test•Women with GDM have high glucose levels in their urine glucosuria• Dipstick testing is widely performed, although it performs poorly• However discontinuing routine dipstick testing has not been shown to cause under diagnosis• Increased GFR during pregnancy contributes to 50% of women having glucose in their urine

How GDM affects the Baby• Affects the mother in late pregnancy, after the baby’s body has been formed but while it is still growing • Gestational Diabetes does not cause the type of birth defects sometimes seen in babies whose mothers had diabetes before pregnancy• If untreated or poorly controlled it can hurt the baby • Although insulin doesn’t cross the placenta, glucose and other nutrients do.• Extra blood glucose crosses the placenta causing high blood glucose levels in the baby • This causes the baby’s pancreas to make extra insulin to get rid of the extra glucose. The extra energy is stored as fat and can lead to macrosomia

19.2 pound baby

Macrosomia• These babies health problems of their own• Damage to shoulder during birth • Newborns may have low glucose levels, because even after birth the baby’s pancreas is producing large amounts of Insulin, which takes up the remaining glucose and leading to Hypoglycemia• They are also at risk of breathing problems• Babies with excess insulin become children who are at risk of developing obesity and adults who are at risk of developing type 2 Diabetes • Macrosomia leads to problems during vaginal deliveries and risk of instrumental deliveries • The development of macrosomia can be evaluated during pregnancy using sonography

• Jaundice• High red blood cell mass (polycythemia)• Low calcium (hypocalcaemia)• Low magnesium (hypomagnesaemia)• Untreated GDM interferes with maturation• Respiratory Distress Syndrome due to incomplete lung maturation and impaired surfactant synthesis

How GDM affects the mother•Women diagnosed with GDM have a high risk of developing DM in the future • Risk is highest in women that required Insulin treatment antibodies associated with diabetes ex. Antibodies against glutamate decarboxylase, islet cells and/or insulinoma antigen 2

Management• Controlling glucose levels• Diabetic diet• G.I diet • Oral medications• But if the above do not work then Insulin therapy may become necessary • Unfortunately treatment of GDM is also accompanied by more infants admitted to the neonatal wards and more inductions of labor• Oral Medications like: • Glyburide (second generation sulfonylurea) has been shown as an effective alternative to insulin therapy• Metformin

Prognosis

• GDM generally resolves once the baby is born• Chances of developing GDM in your second pregnancy after having it in your first are between 30-84% (depending on ethnic background)

In the words of Beyonce Knowles “Strong enough to bare the children, then get back to business”