• Nathan Riley, MD

Obgyno Wino Podcast Episode 3 - Pregestational Diabetes Mellitus

“You matter because you are you, and you matter to the end of your life. We will do all we can not only to help you die peacefully, but also to live until you die.” – Dame Cicely Saunders, nurse, physician and writer, and founder of the hospice movement

2015 Old Vine Zinfandel from Brazin Cellars (2016 vintage pictured)

PB#201 - Published December 2018


- affects 15 million women in the US, which is 3-7% of the reproductive age population

- 1-2% of all pregnancies

- type 1 versus type 2

- type 1: autoimmune destruction pancreatic B cells

- type 2: development of insulin resistance and eventual paucity of insulin, associated with obesity

- 90% of women who develop gestational diabetes will develop Type 2 later in life

- as usual, higher rates in black, Native American, and Hispanic women


- in the first trimester, HgA1C (>6.5% if diagnostic)

- if prevalence of DM is sufficiently high in your practice community, can recommended screening in 1st trimester through 1-hr GCT (50 g load) or testing through fasting glucose or 2-hr GTT (75 g load); otherwise can wait until 24-28 wks w/ other mid-trimester labs

- if 1-hr GCT is abnormal (130-140 mg/dL), recommend 3-hr GTT

- diagnostic values: >126 mg/dL fasting, >200 mg/dL post 2-hr

Pregnancy makes you diabetic

- hormones produced by placenta make you diabetic, worse in 3rd trimester

- both type 1 and type 2

- 1st tri: high levels of estrogen can enhance insulin sensitivity

- hormones: human placental lactogen (aka human chorionicsomatomammotropin), progesterone, prolactin placental growth hormone, TNF-a, leptin, and cortisol

- for this reason, insulin requirements increase significantly in the 3rd tri

What should your patient be doing?

- review fingerstick glucose values q1-2 weeks during 1st and 2nd tri, weekly after 24-28 wks (can be individualized), keep a food log

- check fasting and 1 or 2 hr post-prandial

- exercise! Resistance versus aerobic

- carbohydrate control is important

- 40-50% carbs (high fiber, complex), 15-30% protein, 20-35% fats

- typical daily breakdown of carbohydrate might be: 30-45 g at breakfast, 45-60 g at lunch and dinner, w/ 15 g snacks 2-3 hours after each meal (BUT LET’S BE REAL)

- counting carbs is the best way to tailor insulin regimen to a patient’s specific needs

- goals levels (mean: 100 mg/dL):

≤ 95 mg/dL fasting

≤ 140 1-hr

≤ 120 2-hr

- No less than 60 overnight

- can also repeat HgA1C monthly (PRO TIP: A1c8% reflects mean glucose level of 180)

Benefits of glycemic control

- during embryogenesis may reduce risk of fetal anomalies (more later)

- <6% A1c in the 3rd tri has lowest risk of large-for-gestational-age infants

Prescribing insulin

- 0.7-0.8 units/kg/day in 1st tri

- 0.8-1 units/kg/day in 2nd tri

- 0.9-1.2 units/kg/day in 3rd tri

How I learned to prescribe insulin in relative proportions throughout the day

- general rule: rapid-acting insulin analogues before meals

- normal insulin is short-acting but takes too long to kick in (10-15 min), so Lispro or Aspart (rapid) are preferred

- fewer hypoglycemic episodes with rapid-onset compared to regular insulin

- also a european study showed lower rate of congenital anomalies w/ rapid analogues versus human insulin

- NPH (intermediate) given in AM and qHS maintain basal glucose levels outside of meal time

- better to give qHS than with evening meal as it has been shown to reduce risk of nocturnal hypoglycemia

- long-acting analogues (glargine, detemir) are generally considered safe, but it’s easier to titrate intermediate-acting NPH

A quick note on nocturnal hypoglycemia

- in some patients, particularly if they have an insulin pump, checking glucose around 2-3am may detect nocturnal hypoglycemia

- often patients will then eat a bunch of carbs to correct it resulting in elevated fasting blood sugars: not a good cycle

- caused by excessive basal insulin OR inadequate bedtime snack

- nocturnal HYPERglycemia can be caused by insufficient basal insulin or pump failure

Continuous glucose monitors

- one trial: compared to usual monitoring with fingersticks, CGM shown to decrease risk for neonatal hypoglycemia, to be large for gestational age, or be admitted to the NICU

- another trial: no difference of fetal macrosomia rates but lower rates of preeclampsia

- closed loop systems (CGM + pump) are now available and the limited evidence w/ pregnant women suggests they may lead to fewer hypoglycemic episodes

Patient counseling on hypoglycemia

- educate on signs of hypoglycemia (diaphoresis, ams, dizziness, weakness, fatigue, nausea)

- check glucose, if <60 mg/dL, administer 15 g of carbs (juice, milk, glucose tablets), wait 15 min and check again before taking additional carbs

- glucagon on hand if these efforts fail or if patient loses consciousness Maternal morbidity

- retinopathy, nephropathy, and hypertensive disorders

- retinopathy:

> proliferative: neovascularization, best treated with photocoagulation pre-pregnancy

> non-proliferative: retinal microaneurysms and dot-blot hemorrhages

- progression in pregnancy is seen in about 25% of pre-GDM particularly in patients with concurrent cHTN (particularly in the event of rapid institution of strict glycemic control)

- benefits of glycemic control outweigh risks of progression in the long-run

- nephropathy:

> 5-10% of diabetics

> mild-moderate nephropathy carries low risk of permanent renal deterioration

> severe nephropathy (creatinine >1.5 or >3g proteinuria in 24 hr) in pregnancy carries risk of progression to end stage renal disease

> pre-existing nephropathy is an independent risk factor for: hypertensive disorders, uteroplacental insufficiency, or iatrogenic preterm birth due to worsening renal failure

- cHTN:

> 5-10% of pregnancy pts with pre-GDM

> HTN, esp in presence of nephropathy, increases risk of pre-E, uteroplacental insufficiency, and stillbirth

> ARB and ACE-I contraindicated in pregnancy (adverse fetal effects)

- Pre-GDM is a risk factor for acute MI in pregnancy

- Symptomatic CAD in pre-GDM is most commonly seen in patients with longstanding disease, nephropathy, and hypertension

- severe CAD is a contraindication to pregnancy: as pregnancy-associated hemodynamic changes (increased pre-load, for example) can lead to MI and death

Segment 11 – DKA

- women should check urine ketones if glucose levels >200 mg/dL

- can happen in type 1 or type 2

- occurs in 5-10% of pregnancies affected by pre-GDM and at less severe hyperglycemia or even euglycemia

- risk factors: infections, inappropriate insulin use, insulin pump failure, and treatment with B-mimetic tocolytic medications or antenatal corticosteroids

- medical emergency: abd pain, n/v, AMS

- low pH (<7.3), low bicarb (<15), elevated anion gap, positive serum ketones

- on FHR monitoring, you’ll commonly see minimal variability and/or late decels

- your job? Get ABG to determine degree of acidosis, hourly glucose fingersticks, and serum ketones and electrolytes q1-2 hours, IV hydration and insulin infusion

- regular insulin comparable to aspart or lispro

- commonly we will overcompensate and cause hypokalemia and hypoglycemia (remember: insulin causes intracellular movement of K)

- fortunately, delivery is rarely indicated as the tracing will improve if condition is identified and treated promptly

- fetal mortality historically high, but has vastly improved in recent years

**LR not used because lactate is predominantly metabolized in the liver through gluconeogenesis, which is driven by hydrogen ions. The net result being an improvement of the acidosis but worsening of the hyperglycemia. This hasn’t really panned out in studies and some researchers in the critical care and EM worlds think LR is probably OK. But this is beyond the scope of the practice bulletin…

Perinatal morbidity/mortality

- the longer you have diabetes, the greater likelihood of complications

- presence of end organ damage also predictive

- most common perinatal complication? Congenital anomalies!

- “of all things that we might be exposed to in pregnancy…sugar is one of the most toxic”

(she also purported to hate electric cars because they were too quiet…psh)

- anomalies found in up to 12% of women with pre-GDM

- glycemic control most critical during organogenesis (5-8 wks after LMP), also higher risk of miscarriage early in pregnancy

- HgA1c most predictive. 5-6% carries comparable risk of fetal malformation as unaffected pregnancies (2-3%)

> If 10% --> 20-25% risk of anomalies!!

- anomalies? Complex cardiac defects, CNS anomalies (anencephaly, spina bifida), skeletal malformations (sacral agenesis) most common

- also increased risk for stillbirth

- macrosomia (associated with high post-prandial glucose values and HgA1c)

- doubled risk for shoulder dystocia

Neonatal consequences

- hypoglycemia


- polycythemia: increased serum glucose → increased insulin → increased glucose utilization through aerobic respiration → relative hypoxia → compensation includes increased RBC production

- organomegaly

- electrolyte disturbances

- neural tube defects

Obstetrical issues

- increased risk for primary c-section, preterm birth (particularly in setting of polyhydramnios

- improved outcomes with decreased HgA1c

- Prevalence of preeclampsia in pregnancies complicated by DM1 is 15-20% without preexisting nephropathy and ~50% w/ preexisting nephropathy

Your job as physicians/NP/midwife

- see box 2

- 40% of Type 1 DM have thyroid disorders

- higher doses of folic acid can be considered

- start low dose aspirin at 12 wga (no later than 28 wga) and continued until 36 wga

- fetal monitoring (discussed later)

A note on continuous infusion pumps

Short-acting like Lispro

50-60% continuous

Remaining 40-50% administered with meals

While RCTs have shown some benefit, meta-analyses have shown injections vs continuous pump equivalent

So if a woman is on injections and euglycemic, keep her there. If not? Try a pump

Benefits: less hypoglycemic episodes, better control of hyperglycemia, more flexibility (hasn’t been studied very well in type 2 DM)

Cons: must be highly compliant, $$$, risks w/ pump malfunction

Oral medications

- Not used in type 1 DM

- Not studied in type 2 DM in pregnancy, but biguanides (metformin) and sulfonylureas (glyburide) may be helpful - not FDA approved, cross placenta

- Recall: glyburide → stimulates insulin release from B cells of pancreas; metformin → stimulates insulin release, improves insulin sensitivity in peripheral tissues, decrease glucose absorption from gut

- The data is still mixed on the best treatment for hyperglycemia, though insulin remains the standard

- Initial studies on glyburide showed no difference compared to metformin, though meta-analyses thereafter suggested potentially higher neonatal risks in women treated with glyburide

- 2008: RCT of ~750 women showed no increased risks of neonatal morbidity with metformin

- 2017: Meta-analysis shown metformin has greatest probability of reducing reducing complications compared to both glyburide and insulin

- 2018: Cohort study shown metformin associated with higher risk of congenital anomalies (further stratification found that this association was among women with diabetes versus other indications for metformin like infertility in PCOS)

- 2018: no increased risk of congenital anomalies, stillbirth, or miscarriage in pregnancies managed through oral hypoglycemic agents

- Make no mistake: insulin is still the standard; more data to come, but it looks like it probably safe to continue them if patient is well-controlled going into pregnancy

- “For those women with type 2 diabetes who decline insulin, those who their obstetricians or obstetric care providers believe will be unable to safely administer insulin, or those who cannot afford insulin, metformin (and rarely glyburide) is a reasonable alternative choice in the context of discussing with the patient the limitations of the safety data and a high rate of treatment failure, which requires insulin supplementation”

Fetal assessment/monitoring

- If poorly controlled, always should be concerned with confirmed fetal viability first and foremost (higher risk of miscarriage)

- Formal anatomic survey should take note of cardiac structures and great vessels (higher risk of cardiac anomalies)

- Fetal echo: ~26-28 wga

- Maternal perception of fetal movements is probably sufficient, but reasonable to recommend twice weekly NSTs starting at 32-34 wga

- Growth US at 34 wga and 36-38 wga + fundal heights throughout

- If growth restriction is noted, Doppler velocimetry can be helpful

Timing and mode of delivery

- 36-39 wga may be appropriate if pt has nephropathy or vasculopathy, poor glucose control or history of prior stillbirth

- For others, 39-39.6 reasonable if antenatal testing looks good

- Reasonable to offer cesarean delivery if EFW >4500 gm

- There WAS have been recent meta-analyses that suggest that induction of labor for large for gestational age on sono decreased risk of birth trauma without increasing risk of c-section

Management of labor

- Continuous fetal monitoring (higher risk for adverse outcomes)

- Higher risk for shoulder dystocia even when controlling for birth weight so be prepared and use caution in considering operative assistance

- Early in labor, reasonable to continue current insulin injection dosages, but in active labor, consider an Insulin infusion with goal of 70-110 mg/dL blood glucose at time of delivery (q1 hr fingersticks)

- Type 2 DM may not require insulin

- Type 1 DM always requires insulin!

- If patient has a continuous pump installed, reasonable to continue that throughout labor w/ spot doses PRN

- Recall: Maternal hyperglycemia immediately preceding delivery carries high risk of neonatal hypoglycemia (fetus makes insulin in response to glucose crossing the placenta from mom!)

- If pt becomes hypoglycemic, decrease or discontinue insulin and give Dextrose if needed

- If corticosteroids are administered, higher doses of insulin may be required for the 5 days following administration


- Decrease long-acting or infusion rate by 50%

- When they start eating, decrease the short-acting doses by ⅓ or ½ as well

- Difficulties with lactation common in diabetics

- If serious comorbidities, pt should be counseled ahead of time regarding sterilization, otherwise LARCs


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