ISSUES IN ENDOCRINOLOGY
| MANAGEMENT OF THE OBSTETRIC DIABETIC PATIENT—Steven G. Gabbe, MD, Professor of Obstetrics and
Gynecology and Dean, Vanderbilt University School of Medicine, Nashville, TN
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| Epidemiology: 4% to 7% (or possibly more) of pregnancies in United States complicated by diabetes mellitus (DM);
gestational diabetes mellitus (GDM) accounts for 90% of all diabetes in pregnancy; existing abnormalities of insulin
resistance and defect in insulin release make progression to type 2 diabetes more likely
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| Hormonal changes: late pregnancy state of reduced insulin sensitivity and increased insulin resistance; increased human
placental lactogen, tumor necrosis factor-α, progesterone, prolactin, and cortisol; insulin angiotensin-converting
enzyme (ACE) gene reduces half-life of insulin; pregnant patient responds to insulin resistance by making more β
cells; β cells enlarge and provide more insulin when patient eats; pregnant woman has postprandial hyperglycemia;
glucose crosses placenta based on concentration gradient between mother and fetus; glucose primary fuel for fetus; fetus
sensitive to elevations in glucose; maternal glucose level drops during night; mother breaks down fat for energy,
preserving glucose for fetus (accelerated starvation); presence of ketone bodies in urine indication mother may need
more calories late in day; fetal effects—maternal hyperglycemia leads to fetal hyperglycemia and hyperinsulinemia;
hyperinsulinemia excellent marker for glucose in fetus; insulin major fetal growth hormone; fetus grows larger and
heavier; fat cells accumulate around chest and shoulders (greater risk for shoulder dystocia at delivery and obesity
later in life); macrosomia defined as birth weight >4500 g; problems associated with hyperglycemia in pregnancy—
difficult birth, birth trauma, stillbirth (caused by lactic acidemia in late pregnancy), delayed pulmonary maturation
(can lead to respiratory distress syndrome); fetuses of women with GDM generally not at risk for congenital malformations
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| Definition of GDM: carbohydrate intolerance of variable severity (mild or significant), with onset or recognition during
pregnancy; definition applies whether insulin or glyburide used and whether condition remains after pregnancy;
does not exclude possibility that glucose intolerance may have existed before pregnancy; class A1— women who
maintain normal fasting and postprandial glucose levels with diet alone; no risk for stillbirth; class A2— women who
require insulin or glyburide; risk for stillbirth; patient requiring insulin or glyburide has same risk for stillbirth as pregnant
woman with type 1 or type 2 diabetes
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| Purpose of screening: consequences of GDM—35% to 60% of women with GDM develop type 2 diabetes, especially
in first decade postpartum; one-third of population has undiagnosed type 2 diabetes; screening provides opportunity
to identify and treat at-risk population; all ethnic groups at risk for GDM; data show increased risk for
macrosomia (3 times higher), large-for-gestational-age baby (>3 times higher), and complications in baby (eg, stillbirth,
hypoglycemia; 11 times higher) and risk of shoulder dystocia (4 times higher) in women diagnosed with (but untreated
for) GDM; fetal outcomes no different from those in general population in women diagnosed and treated
appropriately; prevention of maternal hyperglycemia and prevention of fetal hyperglycemia and hyperinsulinemia;
screening reduces macrosomia leading to trauma, including shoulder dystocia; neonates at risk for biochemical abnormalities
(eg, hypoglycemia, hypocalcemia, hyperbilirubinemia); increased risk for stillbirth and long-term morbidity if
condition requires use of insulin or glyburide; long-term consequences—data show mother’s glucose and amniotic
fluid insulin levels predictive of likelihood baby will become overweight later in life; child more likely to develop carbohydrate
intolerance early in teenage years
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| Screening recommendations: American College of Obstetricians and Gynecologists (ACOG) and American Diabetes
Association (ADA) recommend all pregnant women be screened for glucose intolerance; selective screening
based on clinical attributes or past history inadequate; screening consists of detailed history and glucose testing; clinical
characteristics consistent with high risk for GDM—marked obesity, polycystic ovary syndrome (PCOS), history of
GDM, glycosuria, and strong family history of type 2 diabetes; test as soon as possible (can use oral glucose tolerance
test [GTT]); if negative, retest at 24- to 28-wk gestation; fasting glucose >120 mg/dL or hemoglobin A1c (HbA1c )
>7% suggests preexisting diabetes; screening for congenital anomalies with ultrasonography (US); average-risk
patient—test at 24- to 28-wk gestation (when diabetogenic stress present and before fetus becomes larger and
heavier); low-risk patient—<25 yr of age, normal body weight, normal weight at birth, no first-degree relatives with
type 2 diabetes, not member of ethnic group with increased risk for type 2 diabetes, no previous history of abnormal
glucose metabolism, and no history of poor obstetric outcome; confusion of selective screening not practical; blacks,
American Indians, Hispanics, and Asian-Americans at greater risk for type 2 diabetes and GDM
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| Screening for GDM: step 1— 50-g oral glucose challenge between 24- and 28-wk gestation (screen earlier if high
index of suspicion), without regard to time of day or when patient last ate; measure venous plasma glucose 1 hr later
(meters for measuring capillary blood samples not recommended); value of 140 mg/dL indicates need for full diagnostic
GTT; HbA1c not sensitive enough; using 130 mg/dL as cutoff value for 50-g 1-hr challenge increases sensitivity
from 80% to 90%, but increases need for GTT from 15% to 25%; plasma value of >200 mg/dL highly predictive of
GDM (begin treating patient with diet and glucose monitoring); jelly bean test not adequately studied; abnormal
value—administer 3-hr oral GTT; diagnosis requires ≥2 abnormal values (fasting, 1 hr, 2 hr, and 3 hr); O’Sullivan
criteria—cutoff levels 2 standard deviations above mean; shown predictive of perinatal outcome; Carpenter and
Coustan plasma glucose thresholds—closer to O’Sullivan criteria; 95 mg/dL, 180 mg/dL, 155 mg/dL, and 140 mg/dL;
ADA recommends Carpenter and Coustan criteria; ACOG supports either National Diabetes Data Group criteria or
Carpenter and Coustan criteria (speaker prefers Carpenter and Coustan); Hyperglycemia and Adverse Pregnancy Outcome
(HAPO) trial—showed thresholds <105 mg/dL and <200 mg/dL not associated with significant perinatal risk;
babies likely larger and heavier as values increase; question whether thresholds should be lowered; one abnormal
value—treat or repeat oral GTT in 2 to 3 wk; day-to-day variability in glucose tolerance testing
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| Treatment: office visits every 1 to 2 wk until 36 wk, then weekly; dietary management to avoid postprandial
hyperglycemia—2000- to 2200-calorie diet made up of complex carbohydrate foods high in fiber; eliminate concentrated
sweets; 3 meals and bedtime snack; patient should check fasting and 2 hr postprandial glucose levels; nutritional
counseling recommended; exercise—moderate physical exercise ≥30 min daily (10 min after each meal); brisk walking
ideal; aerobic exercise decreases need for insulin, improves glucose level, and controls weight; 60% to 70% of
glucose used by muscles; check fasting urine ketones if patient on calorie-restricted diet; indications for insulin or
glyburide—fasting capillary glucose value >95 mg/dL and/or 1-hr value >140 mg/dL or 2-hr value >120 mg/dL; looking
for pattern of consistently elevated glucose levels; insulin therapy—20 U of NPH and 10 U of regular insulin in
morning and 5 U NPH and 5 U regular insulin at bedtime; insulin lispro (analogue of human insulin) may be used;
Langer formula for calculating insulin dose—1.2 U/kg body weight; glyburide therapy—oral hypoglycemic agent;
sulfonylurea (avoid in patients with sulfa allergies), 2.5 mg daily, starting dosage (can be increased to 2.5 mg bid);
Langer showed glyburide clinically effective alternative to insulin therapy; onset of action ≈4 hr; usually taken in
morning and at dinner if prescribed bid; duration of action, 12 hr; 20 mg maximum daily dosage; most patients require
≈10 mg; bound to protein so it does not cross placenta; risk factors for glyburide failure—diagnosis of GDM at <25-
wk gestation, severe glucose intolerance and insulin resistance, older maternal age, higher gravity, higher parity and
obesity; therapy ineffective in ≈20% of patients; metformin—class B drug; crosses placenta; effective treatment for
PCOS; associated with reduction in GDM among women with PCOS who continue to use metformin throughout pregnancy;
may be continued through 12-wk gestation to decrease risk for miscarriage in patient with PCOS; data did not
show increase in preeclampsia or anomalies with metformin in pregnancy, and GDM less; not associated with adverse
growth patterns, motor skills, or social development; no evidence to recommend metformin therapy for GDM except
in clinical trials
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| Delivery: patient managed by diet—allow to go to term; patients with history of stillbirth or who have hypertension
should have twice weekly fetal monitoring; clinical estimation of fetal size and US indices should be used to detect fetal
macrosomia; evaluate for cesarean delivery if estimated fetal weight >4500 g; patient requiring insulin or
glyburide—greater risk for stillbirth; monitor with antepartum fetal surveillance (similar to that used for women with
pregestational diabetes) starting at 32 wk and initiate twice-weekly fetal monitoring; infant should be observed closely
for hyperglycemia, hypocalcemia, and hyperbilirubinemia; treatment shown beneficial in reducing serious perinatal
morbidity, improving woman’s health-related quality of life, and minimizing costs
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| Postpartum care: ≈15% of women have persistent glucose intolerance or diabetes; 75-g GTT 6 to 12 wk postpartum
(fasting glucose testing several mornings weekly and postprandial glucose testing several days weekly recommended);
normal values—fasting, <100 mg/dL; 2-hr postprandial, <140 mg/dL; impaired glucose tolerance—monitor closely
and treat with dietary management; criteria for diabetes—fasting, 126 mg/dL; 2-hr postprandial, 200 mg/dL; subsequent
testing—75-g GTT 1 yr postpartum recommended; annual fasting glucose if normal; elevated fasting glucose
during pregnancy most predictive for development of type 2 diabetes postpartum; factors associated with more rapid
onset of type 2 diabetes—subsequent pregnancy; body mass index (BMI) >30; use of progestin-only oral contraceptives
(OCs; increase insulin resistance); hypertension and family history of type 2 diabetes; significantly higher mortality
rate due to cardiovascular (CV) disease in women with GDM; diet and exercise mainstays of treatment
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| METABOLIC SYNDROME—Veronica Piziak, MD, PhD, Professor, Departments of Medicine and Endocrinology,
and Director, Division of Endocrinology, Scott & White, Texas A&M Health Science Center College of Medicine, Temple,
TX
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| Metabolic syndrome: characterized by metabolic risk factors that come together as group, predisposing person to
CV disease, diabetes, and hypertension; simple way of assessing patient’s risk for CV event; diagnostic criteria—
insulin resistance, abdominal obesity, dyslipidemia, and elevated blood pressure (BP); waist circumference—>40 in
(men) and >35 in (women) indicative of intra-abdominal fat; glucose—100 mg/dL; low-density lipoproteins (LDL)—
>130; BP—>130 systolic and >85 diastolic
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| Prevalence: increases with age; approximately same prevalence in men and women; by 60 yr of age, almost 45% of
people in United States have metabolic syndrome; highest prevalence among Mexican Americans (36% in women,
28% in men)
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| Consequences: diabetes—prevalence of obesity and diabetes growing in United States; not all obese people develop
diabetes; those with intra-abdominal fat more likely to transition to diabetes; risk correlates with number of characteristics
of metabolic syndrome (4-fold increased risk with 2 characteristics, 7-fold with 3, and 24-fold with 4 or 5); mortality
—patients predisposed to CV events and increased mortality, even when compared to patients with same BMIs
(again, more common in people who have intra-abdominal fat and large waist circumference); C-reactive protein—
intra-abdominal fat metabolically active; raises C-reactive protein, makes inflammatory factors, releases free fatty acids,
and raises insulin levels; creates insulin resistance; hypertriglyceridemia—causes atherogenic changes; small
dense LDL, low high-density lipoprotein (HDL), decreased glucose disposal, and coagulation abnormalities; intra-abdominal
fat contributes to inflammatory process; hyperinsulinemia-insulin resistance—causes hypertension and stimulates
growth of arterial wall; dyslipidemia—increased flux of free fatty acids; raised triglycerides; low HDL; free
fatty acids can be deposited in liver (nonalcoholic hepatitis becoming more common, even in young children)
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| Treatment: 2 approaches; first strategy—modify obesity and physical inactivity; second strategy—directly treat
risk factors (eg, dyslipidemia); treating dyslipidemia—treat LDL first (biggest determinant of macrovascular
events); for patient with high triglycerides, treat non-HDL cholesterol (non–HDL-C); non–HDL-C goal equals
LDL goal plus 30%; evaluation—total cholesterol, HDL, triglycerides, fasting glucose, and thyrotropin; 277.7
code for laboratory reimbursement only; assess patient’s family history; perform physical examination
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| Treating risk factors: exercise and nutrition counselling mainstays of treatment; discuss risks associated with obesity;
change one risk factor at first office visit; hypertension—treat aggressively; 10% reduction in systolic BP lowers
risk for mortality, 7% reduction lowers risk for ischemic heart disease; obtain albumin-to-creatinine ratio (ACR)
whether patient has diabetes or not; microalbuminuria evidence of inflammatory process; ACE inhibitors helpful in
controlling hypertension and preventing diabetes (make sure premenopausal woman using contraception if applicable);
some studies show β-blockers helpful in decreasing risk for diabetes and risk for macrovascular events; avoid
angiotensin II-receptor antagonists; poor diet—caloric restriction key; counsel patient to eliminate sugar from diet;
emphasize fiber-rich foods (eg, fruits, vegetables); low carbohydrate, monounsaturated-fat diet decreases insulin resistance;
diets high in complex carbohydrates and fiber decrease insulin resistance; patient’s food preferences can be
considered when selecting diet; Dietary Approaches to Stop Hypertension (DASH) diet (can be downloaded from
National Kidney Association Web site, www.kidney.org) shown to decrease BP by 6 to 12 mm Hg; increased
clotting—81 mg aspirin daily; smoking cessation—varenicline (Chantix); increased inflammatory factors and
dyslipidemia—statin therapy (do not start at first visit); exercise—30 min of walking 5 times weekly; goals of
therapy—LDL <130 mg/dL (in patients with diabetes, <100 mg/dL); speaker recommends LDL <100 mg/dL in
most patients with metabolic syndrome, <70 mg/dL in patients with diabetes; statin therapy—higher-than-normal
dosage often necessary in people with metabolic syndrome; with, eg, ezetimide and simvastatin (Vytorin), may increase
from normal dosage of 10/40 mg/day to 10/80 mg/day
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Suggested Reading
Anty R et al: Metabolic fatty liver diseases: hepatic consequences of the metabolic syndrome. Gastroenterol Clin
Biol 31:1127, 2007; Buchanan TA et al: What is gestational diabetes? Diabetes Care 30(Suppl 2):S105, 2007;
Gabbe SG et al: Management of diabetes mellitus by obstetrician-gynecologists. Obstet Gynecol 103:1229, 2004;
Jacobson GF et al: Comparison of glyburide and insulin for the management of gestational diabetes in a large
managed care organization. Am J Obstet Gynecol 193:118, 2005; Katcher HI et al: The effects of a whole grain enriched
hypocaloric diet on cardiovascular disease risk factors in men and women with metabolic syndrome. Am J Clin
Nutr 87:79, 2008; Kodaman PH, Duleba AJ: Statins in the treatment of polycystic ovary syndrome. Semin Reprod
Med 26:127, 2008; Kolovou GD el al: Pathophysiology of dyslipidaemia in the metabolic syndrome. Postgrad Med
J 81:358, 2005; Langer O: Management of gestational diabetes: pharmacologic treatment options and glycemic
control. Endocrinol Metab Clin N AM 35:53, 2006; Nathan BM, Moran A: Metabolic complications of obesity in
childhood and adolescence: more than just diabetes. Curr Opin Endocrinol Diabetes Obes 15:21, 2008.
Educational Objectives
| The goal of this program is to improve the diagnosis and management of gestational diabetes mellitus (GDM)
and metabolic syndrome. After hearing and assimilating this program, the clinician will be better able to:
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 | Discuss the metabolic changes associated with pregnancy and the importance of detecting GDM.
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| Diagnose and manage patients with GDM.
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| Manage patients with GDM postpartum.
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| List factors that put patients at risk for metabolic syndrome.
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| Counsel and manage patients with metabolic syndrome.
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Faculty Disclosure
In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty and members of the planning
committee to disclose relevant financial relationships within the past 12 months that might create any personal conflicts of interest.
Any identified conflicts were resolved to ensure that this educational activity promotes quality in health care and not a
proprietary business or commercial interest. For this program, the following has been disclosed: Dr. Piziak has received research
support from, and is on the Speaker’s Bureaus for, Novartis, Procter & Gamble, Sanofi-Aventis, Eli Lilly, and Hoffmann-La
Roche. Dr. Piziak is also on the Speaker’s Bureaus for GlaxoSmithKline and AstraZeneca. Dr. Gabbe and the
planning committee reported nothing to disclose.
Acknowledgments
Dr. Gabbe was recorded at the 33rd Annual High Risk Obstetrics Seminar, sponsored by Vanderbilt University School of
Medicine, and held on November 30 to December 1, 2007, in Nashville, TN. Dr. Piziak was recorded at The Female Patient:
Current Issues in the Care of Women, sponsored by Scott & White and Texas A&M Health Science Center College of Medicine,
and held on June 18-22, 2007, in South Padre Island, TX. The Audio-Digest Foundation thanks the speakers and the
sponsors for their cooperation in the production of this program.
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