Gestational DiabetesThis diagnosis is given when a woman, whohas never had diabetes before, getsdiabetes or has high blood sugar, when sheis pregnant.Its medical name is gestational diabetesmellitus or GDM.It is one of the most common healthproblems for pregnant women.The word “gestational” actually refers to“during pregnancy.” 5 of 42 gdm
As the incidence of type 2 diabetesaccrues with age and is unmasked byother diabetogenic factors, that is,obesity, it is likely that bothpregnancy aggravation andimpending insulinopenia areinvolved.
CHO MetabolismEffects of Pregnancy*Mild fasting hypoglycemia; *Post prandial hyperglycemiaDue to increase in plasma volume in early gestation and increase in fetal glucose utilization.As pregnancy advances -Progressive increase in tissue resistance to insulin – Increase insulin secretion to maintain euglycemia – Suppressed glucagon response – Inc. prolactin, cortisol – HPL has GH like effects
‘Endocrinology of Pregnancy’The placenta produces largerquantities of more hormones thanany other human organ:– Human placental lactogen– Estrogen / progesteroneThe majority of its products arereleased into the maternal circulationto induce changes on the fetuses’behalf.
Glucose Metabolism in PregnancyFetal growth is dependent uponmaternal glucoseCarbohydrates from maternal dietStored glycogen converted toglucoseHigh levels of glucose transported bydiffusion to the fetusFetal production of insulin
Glucose Metabolism in PregnancyFirst Half of Pregnancy (Anabolic) – Pancreatic beta-cell hyperplasia causes hyperinsulinemia – Increased uptake and storage of glucoseSecond Half of Pregnancy (Catabolic) – Placental hormones block glucose receptors and cause insulin resistance Increased lipolysis Increased gluconeogenesis Decreased glycogenesis – Increased glucose and amino acids for the fetus
Maternal and Fetal EffectsThe American College of Obstetricians andGynecologists (2000) defines macrosomic infantsas those whose birthweight exceeds 4500 g.The perinatal goal is avoidance of difficultdelivery due to macrosomia, with concomitantbirth trauma associated with shoulder dystocia.Except for the brain, most fetal organs areaffected by the macrosomia that commonlycharacterizes the fetus of a diabetic woman.
Neonates born from women with consistentlyhigh blood sugar levels are also at an increasedrisk of low blood glucose(hypoglycemia), jaundice, high red bloodcell mass (polycythemia) and low blood calcium(hypocalcemia) and magnesium(hypomagnesemia).Untreated GDM also interferes with maturation,causing dysmature babies prone to respiratorydistress syndrome due to incomplete lungmaturation and impaired surfactant synthesis.
The most important perinatal concern isexcessive fetal growth, which may resultin both maternal and fetal birth trauma.More than half of women with gestationaldiabetes ultimately develop overt diabetesin the ensuing 20 years, and there ismounting evidence for long-rangecomplications that include obesity anddiabetes in their offspring.
There is extensive evidence thatinsulin-like growth factors I (IGF-I)and II (IGF-II) also play a role in theregulation of fetal growth (see Chap.38, Normal Fetal Growth). Thesegrowth factors, which structurally areproinsulin-like polypeptides, areproduced by virtually all fetal organsand are potent stimulators of celldifferentiation and division
Maternal hyperglycemia promptsfetal hyperinsulinemia particularlyduring the second half of gestation,which in turn stimulates excessivesomatic growth. Macrosomia results.Similarly, neonatal hyperinsulinemiamay provoke hypoglycemia withinminutes of birth
Other factors implicated inmacrosomia include epidermalgrowth factor, leptin, andadiponectinMaternal obesity is an independentand more important risk factor forlarge infants in women withgestational diabetes than is glucoseintolerance
Gestational DiabetesIt occurs in about 5% of all pregnancies.If not treated, gestational diabetes can cause health problems for the mother and the fetus. kvr gdm
Gestational DiabetesRisk Factors maternal age >25 Family history glucosuria prior macrosomia previous unexplained stillbirth ethnic group: Hispanic, Black, Asians
ScreeningScreening should be performed between24 and 28 weeks in those women notknown to have glucose intolerance earlierin pregnancy.This evaluation is usually done in twosteps. In the two-step procedure, a 50-goral glucose challenge test is followed by adiagnostic 100-g oral glucose tolerancetest (OGTT) if initial results exceed apredetermined plasma glucoseconcentration.
Fifth International Workshop-Conference on GestationalDiabetes: Recommended Screening Strategy Based on Risk Assessment for Detecting Gestational Diabetes (GDM)GDM risk assessment: Should be ascertained atthe first prenatal visitLow Risk: Blood glucose testing not routinely required if all thefollowing are present:Member of an ethnic group with a low prevalence of GDMNo known diabetes in first-degree relativesAge < 25 yearsWeight normal before pregnancyWeight normal at birthNo history of abnormal glucose metabolismNo history of poor obstetrical outcome
Average Risk Perform blood glucose testing at 24 to 28 weeks using either: —Two-step procedure: 50-g oral glucose challengetest (GCT), followed by a diagnostic 100-g oralglucose tolerance test for those meeting thethreshold value in the GCT.—One–step procedure: Diagnostic 100-g oralglucose tolerance test performed on all subjects.
High Risk: Perform blood glucose testing as soon as feasible, using the procedures described above if one or more of these are present:—Severe obesity—Strong family history of type 2 diabetes—Previous history of GDM, impaired glucosemetabolism, or glucosuria. If GDM is not diagnosed,blood glucose testing should be repeated at 24 to28 weeks or at any time there are symptoms orsigns suggestive of hyperglycemia
DiagnosisRecommended criteria for interpretation ofthe 100-g diagnostic glucose tolerancetest are shown in Table 52-4. Also shownare the criteria for the 75-g test mostoften used outside the United States, butincreasingly used in this country
ManagementWomen with gestational diabetes canbe divided into two functional classesusing fasting glucose levels. Insulintherapy is usually recommendedwhen standard dietary managementdoes not consistently maintain thefasting plasma glucose at < 95mg/dL or the 2-hour postprandialplasma glucose < 120 mg/dL
Whether insulin should be used in women withlesser degrees of fasting hyperglycemia—105mg/dL or less before dietary intervention—isunclear because there have been no controlledtrials to identify ideal glycemia targets forprevention of fetal risks.The Fifth International Workshop Conference onGestational Diabetes, however, recommendedthat maternal capillary glucose levels be kept 95mg/dL in the fasting state
The American Diabetes Association (ADA) (2000) hasrecommended nutritional counseling with individualizationbased on height and weight and a diet that provides anaverage of 30 kcal/kg/d based on prepregnant body weightfor nonobese women.Although the most appropriate diet for women withgestational diabetes has not been established, the ADA hassuggested that obese women with a body mass index (BMI)> 30 kg/m2 may benefit from a 30-percent caloricrestriction. This should be monitored with weekly tests forketonuria, because maternal ketonemia has been linkedwith impaired psychomotor development in offspring
Exerciseexercise is known to be important in nonpregnantpatients exercise improves cardiorespiratory fitnesswithout improving pregnancy outcome.physical activity during pregnancy reduced therisk of gestational diabetes. exercise diminishes the need for insulin therapyin overweight women with gestational diabetes.
researchers findings support the commonpractice of self blood-glucose monitors for womenwith gestational diabetes who are treated withdiet alone.Postprandial surveillance for gestational diabeteshas been shown to be superior to preprandialsurveillance
InsulinInsulin given to decreasecomplications related to macrosomiain women with gestational diabetesand fasting euglycemia has longbeen controversial
Most initiate insulin therapy in women with gestational diabetes iffasting glucose levels exceeding 105 mg/dL persist despite diettherapy.Experts differ in their approach to insulin therapy in gestationaldiabetes. A total dose of 20 to 30 units given once daily, beforebreakfast, is commonly used to initiate therapy.The total dose is usually divided into two-thirds intermediate-acting insulin and a third short-acting insulin.Alternatively, weight-based split-dose insulin is administered twicedaily. Once therapy has been initiated, it must be recognized thatthe level of glycemic control to reduce fetal and neonatalcomplications has not been established.
Oral Hypoglycemic AgentsThe American College ofObstetricians and Gynecologists(2001) has not recommended theseagents during pregnancy.Metformin has been used astreatment for polycystic ovariandisease and has been reported toreduce the incidence of gestationaldiabetes in women who use the drugthroughout pregnancy
Insulin TreatmentInsulin is used for overtly diabetic pregnantwomen. Although oral hypoglycemic agents havebeen used successfully for gestational diabetes(Oral Hypoglycemic Agents), these agents are notcurrently recommended for overt diabetes excepton an investigational basis (American College ofObstetricians and Gynecologists, 2005). Maternalglycemic control can usually be achieved withmultiple daily insulin injections and adjustment ofdietary intake. The action profiles of commonlyused insulins are shown in Table 52-10
It is important to considerably reduce or deletethe dose of long-acting insulin given on the dayof delivery. Regular insulin should be used tomeet most or all of the insulin needs of themother at this time, because insulin requirementstypically drop markedly after delivery. We havefound that continuous insulin infusion bycalibrated pump is most satisfactory (Table 52-13).
During labor and after delivery, the womanshould be adequately hydrated intravenously andgiven glucose in sufficient amounts to maintainnormoglycemia. Capillary or plasma glucoselevels should be checked frequently, and regularinsulin should be administered accordingly. It isnot unusual for a woman to require virtually noinsulin for the first 24 hours or so postpartumand then for insulin requirements to fluctuatemarkedly during the next few days. Infectionmust be promptly detected and treated.
Table 52-5. Glyburide Treatment Regimen for Women with Gestational Diabetes Who Fail Diet Therapy1. Glucometer blood glucose measurements fasting and 1 or 2 hours following breakfast, lunch, and dinner.2. Glucose level goals (mg/dL): Fasting < 100, 1-h < 155, and 2-h < 130.3. Glyburide starting dose 2.5 mg orally with morning meal.4. If necessary, increase daily glyburide dose by 2.5-mg/wk increments until 10 mg/d, then switch to twice-daily dosing until maximum of 20 mg/d reached. Switch to insulin if 20 mg/d does not achieve glucose goals.
Postpartum EvaluationThe Fifth International Workshop Conference onGestational Diabetes recommended that womendiagnosed with gestational diabetes undergoevaluation with a 75-g oral glucose tolerance testat 6 to 12 weeks postpartum and other intervalsthereafter (Metzger and associates, 2007). Theserecommendations are shown in Table 52-6 alongwith the classification scheme of the AmericanDiabetes Association (2003).
Women with a history of gestational diabetes are also at risk forcardiovascular complications associated with dyslipidemia,hypertension, and abdominal obesity—the metabolic syndrome(see Chap. 43, The Metabolic Syndrome).Akinci and associates (2009) reported that a fasting glucose level100 mg/dL with the index OGTT was an independent predictor ofthe metabolic syndrome.
ContraceptionLow-dose hormonal contraceptivesmay be used safely by women withrecent gestational diabetes . The rateof subsequent diabetes in oralcontraceptive users is notsignificantly different from that inthose who did not use hormonalcontraception
ReferencesAdasheck JA, Lagrew DC, Iriye BK, et al: The influence of ultrasound examination atterm on the rate of cesarean section. Am J Obstet Gynecol 174:328, 1996Akinci B, Celtik A, Yener S, et al: Prediction of developing metabolic syndrome aftergestational diabetes mellitus. Fertil Steril January 13, 2009 [Epub ahead of print]Albert TJ, Landon MB, Wheller JJ, et al: Prenatal detection of fetal anomalies inpregnancies complicated by insulin-dependent diabetes mellitus. Am J Obstet Gynecol174:1424, 1996 [PMID: 9065106]Almario CV, Ecker T, Moroz LA, et al: Obstetricians seldom provide postpartumdiabetes screening for women with gestational diabetes. Am J Obstet Gynecol198:528.e1, 2008
American College of Obstetricians and Gynecologists: Gestational diabetes.Practice Bulletin No. 30, September 2001American College of Obstetricians and Gynecologists: Pregestational diabetesmellitus. Practice Bulletin No. 60, March 2005American Diabetes Association: Medical Management of Pregnancy Complicatedby Diabetes, 2nd ed. Jovanovic-Peterson L (ed). Alexandria, VA, AmericanDiabetes Association, 1995American Diabetes Association: Clinical practice recommendations, 1999.Diabetes Care 23:S10, 1999aAmerican Diabetes Association: Report of the Expert Committee on theDiagnosis and Classification of Diabetes Mellitus. Diabetes Care 22:512, 1999b
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