Pre-gestational diabetes N. Shirazian, MD Internist, Endocrinologist.

Pre-gestational diabetes

N. Shirazian, MDN. Shirazian, MDInternist, EndocrinologistInternist, Endocrinologist

pregestational, diabetes (type 1 or type 2) diagnosed before pregnancy

gestational, diagnosed during pregnancy.

Diabetes in pregnant women may be

GDM;

• may merely represent type 2 diabetes that has been unmasked by pregnancy

• does not exclude possibility of unrecognized glucose intolerance may have antedated or begun concomitantly with pregnancy.

• Diabetes after age of 25 years is typically type 2 diabetes.

• ~10% of women with GDM have circulating islet-cell antibodies; may have a "latent" form of type 1 diabetes,

although their risk of developing type 1 diabetes is not known.

• Specific HLA alleles (DR3 or DR4) appear to predispose to development of type 1 diabetes after delivery, as does presence of islet-cell antibodies.

Fasting hyperglycemia;

• at diagnosis of GDM is associated with an increased risk of congenital anomalies

(4.8 versus 1.5 percent in nondiabetic women)

The possibility of undiagnosed pre-gestational diabetes

should be considered in women with;

• fasting hyperglycemia

• fetal anomalies.

Clues to the presence of type 1 diabetes include:

1.GDM in lean women

2.Diabetic ketoacidosis during pregnancy

3.Severe hyperglycemia during pregnancy requiring large doses of insulin

4.Postpartum hyperglycemia

Measurements of

serum anti-insulin antibodies &

anti-islet cell antibodies may be helpful for identifying type 1 diabetes in pregnant women

Women who have these antibodies during pregnancy should be advised to continue self

blood glucose monitoring postpartum to document persistent hyperglycemia.

Prepregnancy evaluation & counseling

in pregestational diabetes mellitus

(type 1 or type 2) is critical

to minimize the risk to the fetus and mother

Testing —1.  Routine prenatal laboratory evaluations

2. Assessment for & treatment of asymptomatic bacteriuria is particularly important because there is a 3-5 fold greater propensity for asymptomatic bacteriuria in diabetic women.

3. A1C.

4. Baseline renal function, initial quantification of urinary proteinuria in a random urine sample using the urinary protein-to-creatinine ratio. This method is both reproducible and more convenient for the patient than a 24-

hour collection.

5. TSH & free T4, incidence of thyroid dysfunction in type 1 diabetes is as high as 40 %

6. ECG,

7. Dilated, comprehensive eye examination

pregestational diabetes

• Unfortunately, many pregnancies are unplanned • severity can be categorized according to White classification,

which has some correlation with pregnancy outcome

• simpler categorization of

"vascular disease present" "vascular disease absent" because placental dysfunction (and

its sequelae preeclampsia and/or fetal growth restriction) and aggravation of maternal end-organ disease are more common in women with vasculopathy

Lawrence, JM et al; Trends in the prevalence of preexisting diabetes and gestational diabetes mellitus among a racially/ethnically diverse population of pregnant women, 1999-2005. Diabetes Care 2008;31:899.

retrospective study,175,249 pregnancies proportion of preGDM rose from 10 % in 1999 to 21 % in 2005, after adjustment for age and race/ethnicity.

overall prevalence of preGDM;

increased from 0.81 % in 1999 to 1.82 % in 2005. the prevalence of GDM remained constant ~ 7.5 % in same interval

• In addition to fetal complications, physiological changes associated with pregnancy can adversely impact maternal health.

• Retinopathy,

• nephropathy,

• hypertension,

• neuropathy,

• cardiovascular disease,

• thyroid disease can all affect & be affected by pregnancy.

Effect of pregnancy on microvascular in diabetes control and complication trial.

DCCT research group. Diabetes Care2000; 23:1084

• a multicenter controlled clinical trial • intensive treatment vs conventional therapy • 180 with 270 pregnancies• 500 who did not become pregnant • an average of 6.5 years of follow-up.

• conventional treatment group changed to intensive therapy if they were planning pregnancy or as soon as possible after conception.

• Fundus photography performed q 6 months urinary albumin excretion rate (AER) measured annually

Effect of pregnancy on microvascular in diabetes control and complication trial.

DCCT research group. Diabetes Care2000; 23:1084

• likelihood of worsening retinopathy was significantly

greater during pregnancy & in first year postpartum.

• risk was higher in whom receiving conventional therapy before pregnancy than in those receiving intensive therapy (OR 2.5 versus 1.6),

RESULTS:

• In conventional group, odds of ≥ 3-step progression from the baseline retinopathy level was >2.9-fold among pregnant vs. not pregnant women (P = 0.003).

•

• odds ratio (OR) peaked during the second trimester (OR = 4.26, P = 0.001) & persisted as long as 12 months postpregnancy (OR = 2.87, P = 0.005)

• a small number required laser photocoagulation during pregnancy.

Despite short-term risks,

long-term risk of progression

( ~ 6.5 years of follow-up)

was not different among women

who did or did not become pregnant.

DCCT• first large prospective study to assess the effect of pregnancy on

development & progression of diabetic retinopathy & microalbuminuria.

1. younger,

2. shorter duration of diabetes, 3. fewer and/or less severe complications than patients in virtually all other

studies that have examined the effects of pregnancy on diabetic complications.

4. in intensive treatment group, HbAI was in normal or nearnormal range for an average of 3 years before conception.

• Therefore, DCCT cohort was less affected by known risk factors for development or progression of retinopathy and/or albuminuria.

2 large prospective studies of women with type 1 diabetes,

• Effect of pregnancy on microvascular in diabetes control and complication trial. DCCT research group. Diabetes Care2000; 23:1084

• Verier-Mine,o,et al; Is pregnancy a risk factor for microvascular complications? The EURODIAB Prospective complications study. Diabetes Medicine2005;22:1503

• pregnancy was not a risk factor for development of early nephropathy, retinopathy, or neuropathy after adjusting for

confounders such as age, duration of diabetes, & A1C

• It is a critical factor affecting outcome of pregnancy in diabetic women

• in ~ 6 % of pregnant women with type I diabetes

diabetic nephropathy in pregnancy;

• Whether pregnancy causes a worsening of diabetic nephropathy or hastens progression to end-stage renal disease is controversial.

• Historically, women with nephropathy, especially those with preexisting hypertension, were discouraged from pregnancy.

• most modern studies have demonstrated maternal & perinatal outcomes are very good.

Proteinuria —

•  Normal pregnancy increase up to 60 % in GFR & a small increase in urinary protein excretion.

• amount of proteinuria in women with diabetic nephropathy also typically increases as pregnancy progresses, & regresses to or near prepregnancy levels after delivery.

• Also in microalbuminuria.

Renal function —

• Many experience a temporary decline in renal function during gestation, pregnancy per se does not appear to hasten natural

progression to end-stage renal disease for most women;

• • this depends upon the initial degree of renal

impairment.

• In mild renal dysfunction (cr < 1.4 mg/dL) prior to pregnancy are likely to maintain stable renal function throughout pregnancy.

• In moderate to severe renal insufficiency typically rise

in creatinine occurs by third trimester & may persist postpartum.

• In women with only microalbuminuria.

• DCCT,

• Pregnancy did not affect long-term rate of progression of underlying nephropathy, as measured by albumin excretion,

in women with microalbuminuria.

• The EURODIAB IDDM Complications Study also found that pregnancy was not a risk factor for development of microalbuminuria or long-term progression of nephropathy in woman with no nephropathy or microalbuminuria at baseline

Hypertension prevalence of preeclampsia in preGDM;

• with vascular disease =17%

• without vascular disease = 8 %,

• compared to a rate of 5 - 8 %

in nondiabetic pregnancies

Cardiovascular disease• diabetes & frequent presence of other risk factors

have an increased risk for atherosclerosis • diabetic women with coronary heart disease are more likely to be

asymptomatic than nondiabetic patients with coronary heart disease

• Pregnancy confers increased demands on heart & CHD carries a high risk of maternal mortality; so, assessment of cardiovascular status is important, even in young women.

Thyroid disease

•  There is a well described association between diabetes & immune-mediated thyroid dysfunction

• risk of developing thyroid dysfunction is 5 -10 % annually in women with type 1 diabetes.

Peripheral & autonomic neuropathy

• Pregnancy does not affect course of somatic or autonomic neuropathy

• women with neuropathy (autonomic or peripheral) are at increased risk of pregnancy complications, such as hyperemesis gravidarum (related to gastroparesis), hypoglycemia unawareness, orthostatic hypotension,

urinary retention, & carpal tunnel syndrome.

• cardiovascular adjustments to pregnancy may be impaired in women with diabetic neuropathy; ex, normal increases in cardiac output & blood volume may not occur

infection• in nonpregnant diabetic women, especially those with

poor glycemic control or end-organ damage & UTI are likely to be more severe in diabetic than nondiabetic.

Infection increases risk of developing;

• preterm labor • diabetic ketoacidosis, can cause fetal death in addition to

maternal morbidity.

Any comment?