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GESTATIONAL DIABETES MELLITUS By DR SUSHANT YADAV Resident in Department of Medicine MGM Medical College, Aurangabad

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Page 1: Gestational diabetes mellitus by sushant

GESTATIONAL DIABETES MELLITUS

ByDR SUSHANT YADAV

Resident in Department of MedicineMGM Medical College, Aurangabad

Page 2: Gestational diabetes mellitus by sushant

DEFINITION AND CLASSIFICATION OF DIABETES MELLITUSo Diabetes mellitus is a metabolic disorder

caused by defects in insulin secretion or action, which lead to abnormalities in the metabolism of carbohydrates, lipids and protein (ADA, 2008a).

o Chronic hyperglycemia associated with diabetes causes tissue damage in all organ systems.

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TYPE 1 DIABETES

o An immune-mediated disorder characterized by destruction of the beta cells of the pancreas, which leads to an absolute insulin deficiency.

o Accounts for 5 percent to 10 percent of all diabetes and 1 percent of diabetes in pregnancy (ADA, 2008 a; Lethbridge-Cejku et al., 2004).

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TYPE 2 DIABETESo Is the most prevalent form of diabetes,

accounting for 90 percent to 95 percent of cases (CDC, 2008)

o Is a disease of insulin resistance and relative insulin deficiency.

o Can be controlled with lifestyle modification and oral medications.

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DIABETES IN PREGNANCY: TYPES Gestational Diabetes Mellitus (GDM)

Type A1: abnormal oral glucose tolerance test (OGTT) but normal blood glucose levels during fasting and 1-2 hours after meals; diet modification is sufficient to control glucose levels

Type A2: abnormal OGTT compounded by abnormal glucose levels during fasting and/or after meals; additional therapy with insulin or other medications is required

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DIABETES IN PREGNANCY: CLASSIFICATION

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DIABETES IN PREGNANCY: CLASSIFICATION…

White’s Group A: Diabetes existing prior to or detected during pregnancy, needing only diet, no insulin treatment being necessary.

White’s Group A/B: Diabetes appearing before or during pregnancy, insulin treatment becoming necessary during pregnancy.

White’s Group B: Diabetes pre-existing and necessitating insulin treatment before conception, onset of diabetes after maternal age of 20 years, and/or duration of diabetes shorter than 10 years.

Pedersen J. The pregnant diabetic and her newborn.Problems and management. 2nd ed. Baltimore: Williams and Wilkins, 1977.

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White’s Group C: Duration of 10-19 years and/or onset of diabetes between 10-19 years of maternal age, insulin dependent diabetes. (These four groups are characterized by the absence of diabetic angiopathy.)

White’s Group D: Onset insulin dependent Diabetes before the age of 10 years and/or duration exceeding 20 years. All pregnant mothers with discernible but not proliferative diabetic retinopathy are classified as group D.

White’s Group F: Severe proliferative diabetic retinopathy and/or diabetic nephropathy before or during pregnancy.

DIABETES IN PREGNANCY: CLASSIFICATION…

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GESTATIONAL DIABETES MELLITUS (GDM) Gestational Diabetes Mellitus (GDM) is defined as

‘carbohydrate intolerance with recognition or onset during pregnancy’, irrespective of the treatment with diet or insulin.

Many are denovo pregnancy inducedSome are type 2 ( 35-40%)10% have antibodies

The importance of GDM is that two generations are at risk of developing diabetes in the future.

Women with a history of GDM are at increased risk of future diabetes, predominately type 2 diabetes, as are their children.

Yogev Y, Chen R, Langer O, Hod M. Diurnal Glycemic profile characterization in non diabetic non obese subjects during the first trimester. The 37th Annual

Meeting of the Diabetes And Pregnancy Study Group, Myconos – Hellas: September, 2005.

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EPIDEMIOLOGY GDM happens in about 7 of every 100 pregnancies.

The recent data on the prevalence of GDM in India was 16.55% by WHO criteria of 2 hr PG ≥ 140 mg/dl

Significant disturbances in carbohydrate metabolism occur in about 1 % pregnancies

The incidence of GDM increases by approximately 8 times for pregnant women aged 35 years and over compared with women aged 25 years or under

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MAGNITUDE OF PROBLEM: GLOBAL Prevalence of GDM varies worldwide and

among different racial and ethnic groups within a country.

America – white women (3.9%) Asian (8.7%) Europe – 0.6% to 3.6% Australia – 3.6% to 4.7% China – 2.3%; Japan – 2.9%

Variability is partly because of the different criteria and screening regimens

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PATHOPHYSIOLOGY The maternal metabolic adaptation is to maintain the

mean fasting plasma glucose of 74.5 ± 11 mg/dl and the post prandial peak of 108.7 ± 16.9mg/dl.

This fine tuning of glycemic level during pregnancy is possible due to the compensatory hyperinsulinaemia, as the normal pregnancy is characterized by

Increased insulin resistance andDecreased insulin sensitivity.

A pregnant woman who is not able to increase her insulin secretion to overcome the insulin resistance that occurs even during normal pregnancy develops gestational diabetes.

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PATHOPHYSIOLOGY…

INCREASED INSULIN RESISTANCE

o Due to hormones secreted by the placenta that are “diabetogenic”:

Growth hormone Human placental lactogen Progesterone Corticotropin releasing hormone

o Transient maternal hyperglycemia occurs after meals because of increased insulin resistance.

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PATHOPHYSIOLOGY…Relative baseline hypoglycemia

o Proliferation of pancreatic beta cells (insulin-secreting cells) leads to increased insulin secretion. Insulin levels are higher than in pregnant than

nonpregnant women in fasting and postprandial states.

o Hypoglycemia between meals and at night because of continuous fetal draw Blood glucose levels are 10-20% lower.

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PATHOPHYSIOLOGY… 24-hour insulin requirement before conception is

approximately 0.6 units / kg. In the first trimester, the insulin requirement rises to

0.7units / kg of the pregnant weight – more unstable glycemia with a tendency to low fasting plasma glucose and high postprandial excursions and the occurrence of nocturnal hypoglycemia.

By the second trimester, the insulin requirement is 0.8 units per kilogram. From 24th month onwards steady increase in insulin requirement and glycemia stabilizes.

By third trimester the insulin requirement is 0.9 - 1.0 unit /kg pregnant weight per day.

Last month – may be a decrease in insulin and hypoglycemias esp. nocturnal.

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PATHOPHYSIOLOGY…

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RISK FACTORSa) Positive family history of diabetes (parents or sibling). Family

history should include uncles, aunts and grand parentsb) Having previous birth of an overweight baby of 4 kg or morec) Previous stillbirth with pancreatic islet hyperplasia revealed

on autopsyd) Unexplained perinatal losse) Presence of polyhydroamnios or recurrent vaginal

candidiasis in present pregnancyf) Persistent glycosuriag) Age over 30 yearsh) Obesityi) Polycystic ovary syndrome j) Current use of glucocorticoids k) Essential hypertension or pregnancy-related hypertension

American Diabetes Association. Gestational diabetesmellitus. Diabetes Care 2003;26 (suppl):S103-5.

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SCREENING American Diabetes Association (ADA) recommends

two step procedures for screening and diagnosis of diabetes and that too in selective (high risk) population.

Compared with selective screening, universal screening for GDM detects more cases and improves maternal and neonatal prognosis.

In the Indian context, screening is essential in all

pregnant women as the Indian women have 11 fold increased risk of developing glucose intolerance during pregnancy compared to Caucasian women.

Cosson E, et al. Screening and insulin sensitivity in gestationaldiabetes. Abstract volume of the 40th Annual Meeting of the

EASD, September 2004: A 350.

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SCREENING… Practically all the pregnant women should undergo

screening for glucose intolerance.

The usual recommendation for screening is between 24 and 28 weeks of gestation.

The recent concept is to screen for glucose intolerance in the first trimester itself as the fetal beta cell recognizes and responds to maternal glycemic level as early as 16th week of gestation.

If found negative at this time, the screening test is to be performed again around 24th – 28th week and finally around 32nd – 34th week

Nahum GG, Wilson SB, Stanislaw H. Early-pregnancy glucose screening for gestational

diabetes mellitus. J Reprod Med 2002;47:656-62.

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SCREENING… American Diabetes Association (2003) recommends 3

hour 100 gm OGTT and Gestational Diabetes Mellitus is diagnosed if any 2 values meet or exceed FPG > 95 mg/dl, 1 hr PG > 180 mg/dl, 2 hr PG > 155 mg/dl and 3 hr PG > 140 mg/dl.

This criteria was originally validated against the future risk of these women developing diabetes and not on the fetal outcome.

Now according to recent ADA guidelines 2012, it is recommended that a 2 hour OGTT with 75 gm glucose should be used for screening.

American Diabetes Association. Gestational diabetes

mellitus. Diabetes Care 2003;26 (suppl):S103-5.

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SCREENING…The reason for this change is that- When a glucose tolerance test is administered to

non-pregnant individuals, it is standard to use the 75-g, 2-hour OGTT.

Using a different glucose challenge in pregnant versus non-pregnant patients leads to confusion in the laboratory and may result in errors in applying the proper diagnostic criteria.

Further, the 75g, 2-hour OGTT is in use during pregnancy in many countries around the world, typically using the same thresholds as in non-pregnant individuals.

Coustan, Donald R. MD, “Making the diagnosis of Gestational Diabetes Mellitus (Diabetes and

Pregnancy)”. Clin Obstet Gynecol 2000;43:99-105.

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ADA GUIDELINES 2012 FOR GDM SCREENING…

Screen for undiagnosed type 2 diabetes at the first prenatal visit in those with risk factors, using standard diagnostic criteria.

In pregnant women not previously known to have diabetes, screen for GDM at 24–28 weeks’ gestation, using a 75-g 2-h OGTT and the diagnostic cut points.

American Diabetes Association. Standards of Medical Care in Diabetes 2012 Diabetes Care 2012;35

(suppl):S12-63.

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ADA GUIDELINES 2012 FOR GDM SCREENING… Screen women with GDM for persistent diabetes at 6–

12 weeks’ postpartum, using a test other than A1C.

Women with a history of GDM should have lifelong screening for the development of diabetes or prediabetes at least every 3 years.

Women with a history of GDM found to have prediabetes should receive lifestyle interventions or metformin to prevent diabetes.

American Diabetes Association. Standards of Medical Care in Diabetes 2012 Diabetes Care 2012;35

(suppl):S12-63.

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ADA GUIDELINES 2012 FOR GDM SCREENING… These new criteria will significantly increase the

prevalence of GDM, primarily because only one abnormal value, not two, is sufficient to make the diagnosis.

ADA recognizes the anticipated significant increase in the incidence of GDM diagnosed by these criteria and is sensitive to concerns about the “medicalization” of pregnancies previously categorized as normal.

These diagnostic criteria changes are being made in the context of worrisome worldwide increases in obesity and diabetes rates, with the intent of optimizing gestational outcomes for women and their babies. American Diabetes Association. Standards of Medical

Care in Diabetes 2012 Diabetes Care 2012;35 (suppl):S12-63.

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ADA GUIDELINES 2012 FOR GDM SCREENING… Admittedly, there are few data from randomized

clinical trials regarding therapeutic interventions in women who will now be diagnosed with GDM based on only one blood glucose value above the specified cut points (in contrast to the older criteria that stipulated at least two abnormal values).

However, there is emerging observational and retrospective evidence that women diagnosed with the new criteria (even if they would not have been diagnosed with older criteria) have increased rates of poor pregnancy outcomes similar to those of women with GDM by prior criteria

Lapolla A, DalfràMG, Ragazzi E, De Cata AP, Fedele D. New International Asso- ciation of the Diabetes and Pregnancy Study Groups (IADPSG) recommendations for diagnosing

gestational diabetes compared with former criteria: a retro- spective study on pregnancy outcome.Diabet Med2011;28:1074–1077.

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DIAGNOSTIC CRITERIA

Nakabayashi M, et al. Changed diagnostic criteria for gestationaldiabetes mellitus. Acta Obstetrica et Gynaecologica Japonica.

2010;62:1525. .

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DIAGNOSTIC CRITERIA

Nakabayashi M, et al. Changed diagnostic criteria for gestationaldiabetes mellitus. Acta Obstetrica et Gynaecologica Japonica.

2010;62:1525.

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COMPLICATIONS• Maternal • Fetal

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MATERNAL COMPLICATIONS Diabetes complications during pregnancy:

1. Diabetic ketoacidosis 2. Deterioration of diabetic retinopathy 3. Deterioration of diabetic nephropathy 4. Hypoglycemia (when using insulin)

Obstetric complications during pregnancy: 1. Spontaneous abortion.2. Premature birth3. Pregnancy-induced hypertension4. Polyhydramnios5. Maternal distress

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MATERNAL COMPLICATIONS… Obstetric complications during labour:1. Prolonged labour 2. Shoulder dystocia3. Perineal injuries4. Postpartum haemorrhage5. Operative interference

Obstetric complications in puerperium:1. Puerperal sepsis2. Failing lactation

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FETAL COMPLICATIONS Antenatal complications:

1. Fetal distress/fetal death2. Congenital malformations- Cardiac abnormalities (ventricular

atrial septal defects), Neural tube defects, (anencephaly, spina bifida, microcephaly) and Caudal regression syndrome (sacral agenesis)

3. Macrosomia4. Delayed fetal development

Complication during birth:1. Birth injury due to shoulder dystocia

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FETAL PROBLEMS ASSOCIATED WITH MATERNAL HYPERGLYCEMIA ACCORDING TO TRIMESTERS OF GESTATION

FIRST TRIMESTER SECOND TRIMESTER

THIRD TRIMESTER

Malformations Growth

Retardation Fetal Wastage

Hypertrohic Cardiomyopathy

Polyhydramnios Erythremia Placental

Insufficiency Preeclampsia Fetal loss Low IQ

Hypoglycemia Hypocalcemia Hyperbilirubinemia Respiratory Distress

Syndrome Macrosomia Hypomagnesemia Intrauterine death

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MANAGEMENT• Examination• Investigations• Non-pharmacological• Pharmacological

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EXAMINATION Physical findings: blood pressure, heart rate, weight

(measured every day while the patient is hospitalized)

Height of uterine fundus measured once per week

Pelvic examination: check for indications of premature birth; vaginal culture

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INVESTIGATIONS Blood and urine testing

a. Self-monitoring of blood glucoseb. HbA1c, KFT, peripheral blood in general: measured once per month.c. Anti-insulin antibody, anti-GAD antibody, islet cell antibody (ICA):

carried out once as early in the pregnancy as possible.d. Urine protein, quantitative measurement of urinary glucose: twice

per monthe. Urine ketone bodies, protein, qualitative measurement of urinary

glucose: twice per weekf. Blood ketone bodies: once per monthg. Trace urinary albumin: early pregnancy

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INVESTIGATIONS… Self-monitoring of blood glucose (SMBG)

As a rule, blood glucose is measured 7 times per day. Blood glucose testing times: before each meal, 2 hours after each meal (2 hours after the start of the meal), and before going to sleep at night.

Depending on the patient’s symptoms, blood glucose may also be measured at 2 a.m. or 3 a.m.; in the case of mild glucose intolerance symptoms, blood glucose may be measured 4 times per day.

In the case of patients with type 1 diabetes, blood glucose is measured 6–7 times per day throughout the pregnancy.

While hospitalized, the values obtained with self-monitoring of blood glucose are checked against laboratory blood glucose values once to check consistency

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HbA1C Provides valuable supplementary information for glycemic

control To safely achieve target glucose levels, combine A1C with

frequent self-monitoring of blood glucose (SMBG)1,2

Recent research suggests weekly A1Cs during pregnancy:1

SMBG alone can miss certain high glucose values SMBG + A1C = more complete data for glucose control Clinicians can further optimize treatment decisions with weekly A1C

INVESTIGATIONS…

1. Jovanovic L, et al. Diabetes Care. 2011;34(1):53-54. 2. Castorino K, Jovanovic L. Clin Chem. 2011;57(2):221-30.3. Lowe LP, et al. Diabetes Care. 2012;35:574-580.

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Continuous Glucose Monitoring Systems (CGMS)• A temporary sensor implanted subcutaneously makes it

possible to measure glucose in the interstitial fluid.

• CGMS cannot replace SMBG; they can, however, provide more information on the diurnal variation in blood glucose than SMBG.

• Indications for use of CGMS in pregnancy: Frequent episodes of hypo- or hyperglycemia Diabetic ketoacidosis Lack of correlation between reported blood glucose and

A1C Improved glycemic control during third trimester Reduced infant birth weight Decreased risk of infant macrosomia1,2,3

INVESTIGATIONS…

1. Hod M. Jovanovic L. Int J Clin Pract, 2010;64(166):47-52. 2. Castorino K, Jovanovic L. Clin Chem. 2011;57(2):221-30.3. Chitayat, L, et al. Diabetes Technology & Therapeutics. 2009;11:S105-111. 4. AACE. Endocr Pract. 2010;16(5):1-16.

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Urine-ketone Testing• To ensure adequate intake ruling out starvation ketosis,

pregnant women should test urine for ketones daily from the first void.

• Hyperglycemic levels >200 mg/dl warrant ketone testing.

• Hyperglycemia and ketosis may indicate an infection and should be evaluated thoroughly.

Examination of the ocular fundus• Once per month if blood glucose control is poor.

INVESTIGATIONS…

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INVESTIGATIONS…Fetal ultrasound Measurement of fetal development Fetal congenital malformations Check for presence of hydramnios. Evaluation of fetal well-being- Non-stress Test (NST),

Biophysical profile scoring (BPS) Assessment of fetal maturity- Amniocentesis for assessing

the lecithin to Sphingomyelin (L:S) ratio.

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GOALS FOR GLYCEMIC CONTROL As regards goals for glycemic control for women with GDM,

recommendations from the Fifth International Workshop- Conference on Gestational Diabetes are to target maternal capillary glucose concentrations of:

Preprandial: ≤95mg/dL (5.3mmol/L), and either:

1-h postmeal: ≤ 140mg/dL (7.8mmol/L) or

2-h postmeal: ≤ 120mg/dL (6.7mmol/L)

American Diabetes Association. Standards of medical care in

diabetes – 2011. Diabetes Care 2011;34(suppl 1):S11-12.

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GOALS FOR GLYCEMIC CONTROL… For women with preexisting type 1 or type 2 diabetes who

become pregnant, a recent consensus statement recommended the following as optimal glycemic goals, if they can be achieved without excessive hypoglycemia:

Premeal, bedtime, and overnight glucose 60–99 mg/dL (3.3–

5.4 mmol/L)

Peak postprandial glucose 100–129 mg/dL (5.4–7.1 mmol/L)

A1C ,6.0%

American Diabetes Association. Standards of medical care in

diabetes – 2011. Diabetes Care 2011;34(suppl 1):S11-12.

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NON-PHARMACOLOGICAL TREATMENTDiet therapy: During pregnancy, as pregnant women patients need to

consume adequate energy, protein, and minerals

Either low-carbohydrate, low-fat calorie-restricted, or Mediterranean diets may be effective in the short-term

For patients on low-carbohydrate diets, monitor lipid profiles, renal function, and protein intake (in those with nephropathy), and adjust hypoglycemic therapy as needed.

Recommendation for dietary fiber (14 g fiber/1,000 kcal) and foods containing whole grains (one-half of grain intake).

American Diabetes Association. Standards of medical care in

diabetes – 2011. Diabetes Care 2011;34(suppl 1):S11-12.

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Diet therapy: The diet schedule must be planned in such a way as to prevent

postprandial hyperglycemia.

Diabetic fetopathy which is the result of maternal postprandial hyperglycemia can be minimized when the peak postprandial response is blunted.

The peak postprandial response is minimized in a woman with gestational diabetes if her meal plan is carbohydrate restricted.

Saturated fat intake should be ,7% of total calories.

Reducing intake of trans fat lowers LDL cholesterol and increases HDL cholesterol, therefore intake of trans fat should be minimized.

NON-PHARMACOLOGICAL TREATMENT

American Diabetes Association. Standards of medical care in

diabetes – 2011. Diabetes Care 2011;34(suppl 1):S11-12.

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Medical Nutrition Therapy (MNT)• MNT by a registered dietitian is the cornerstone for

diabetes management in women with pregestational and gestational diabetes.

• The nutritional management of women with preexisting and gestational diabetes does not differ and has the same therapeutic goals: adequate nutrition and weight gain, plus prevention of ketosis and postprandial hyperglycemia.

• The diet for a pregnant woman with diabetes includes at least 175 g/day of carbohydrate, 28 g/day of fiber and 1.1 g of protein per kg/day (Reader & Thomas, 2008).

NON-PHARMACOLOGICAL TREATMENT

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Medical Nutrition Therapy (MNT)• All pregnant women should take a prenatal vitamin

with 600 mcg of folic acid daily (IOM, 1998).

• All pregnant women should limit caffeine to 200 mg/day.

• After a thorough assessment, the dietitian and the woman develop an individualized meal plan to achieve desired treatment goals.

• The dietitian and the woman examine and discuss lifestyle influences that have a bearing on MNT.

NON-PHARMACOLOGICAL TREATMENT

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NON-PHARMACOLOGICAL TREATMENTExercise:

Patients GDM should be referred to an effective ongoing support program targeting weight loss of 7% of body weight and increasing physical activity to at

least 150 min per week of moderate activity such as walking.

American Diabetes Association. Standards of medical care in

diabetes – 2011. Diabetes Care 2011;34(suppl 1):S11-12.

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PHARMACOLOGICAL TREATMENT When MNT alone fails, pharmacologic therapy is indicated

AACE guidelines recommend insulin as the optimal approach1

Insulin therapy is required for the treatment of T1DM during pregnancy2

Metformin and the sulfonylurea glyburide are the 2 most commonly prescribed oral antihyperglycemic agents during pregnancy.

Due to efficacy and safety concerns, the ADA does not recommend oral antihyperglycemic agents for gestational diabetes mellitus (GDM) or preexisting T2DM

Medication

Crosses Placenta

Classification Notes

Metformin Yes Category B1 Metformin and glyburide may be insufficient to maintain normoglycemia at all times, particularly during postprandial periods2

Glyburide Minimaltransfer

Some formulations category B,others category C1,5,6

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PHARMACOLOGICAL TREATMENTMetformin therapy for prevention:

Metformin therapy for prevention of type 2 diabetes may be considered in those women with prior GDM.

It was as effective as lifestyle in women with a history of GDM, metformin and intensive lifestyle led to an equivalent 50%reduction in the risk of diabetes

Metformin therefore might reasonably be recommended for very-high-risk individuals (those with a history of GDM, the very obese, and/or those with more severe or progressive hyperglycemia).

American Diabetes Association. Standards of medical care in

diabetes – 2011. Diabetes Care 2011;34(suppl 1):S11-12.

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PATIENT EDUCATION• Insulin administration, dietary modifications in response to self-monitoring

of blood glucose (SMBG), hypoglycemia awareness and management.BASAL INSULIN• Intermediate- or long-acting insulin administered by injection, or• Rapid-acting insulin administered by insulin pump2,3

POSTPRANDIAL HYPERGLYCEMIA• Recommended approach: rapid-acting insulin analogues2

• Alternative approach: regular insulin to control postprandial glucose spikes; must be administered 60-90 minutes prior to meals (considered less effective than rapid-acting insulin and may increase hypoglycemia risk)3

INSULIN OPTIONS• Insulin NPH: safe intermediate alternative (category B)2

• Insulin detemir: safe long-acting alternative (category B)2,3

• Lispro and aspart: safe rapid-acting insulin analogues (category B)2,3

• Insulin glargine: frequently prescribed in pregnancy; however, safety in pregnancy has not been definitively established (category C)2,3

PHARMACOLOGICAL TREATMENT- INSULIN USE DURING PREGNANCY

1. Jovanovic L, et al. Mt Sinai J Med. 2009;76(3):269-80. 2. AACE. Endocr Pract. 2011;17(2):1-53.3. Castorino K, Jovanovic L. Clin Chem. 2011;57(2):221-30. 4. ADA. Diabetes Care. 2004;27(suppl 1):S88-90.

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PHARMACOLOGICAL TREATMENT-INITIATION OF INSULIN

GLUCOSE LEVELS FOR INSULIN INITIATION IN GDM1

Fasting plasma glucose ≤105 mg/dL(5.8 mmol/L)

1-hour postprandial plasma glucose ≤155 mg/dL(8.6 mmol/L)

2-hour postprandial plasma glucose ≤130 mg/dL(7.2 mmol/L)

1. ADA. Diabetes Care. 2004;27(suppl 1):S88-90.

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PHARMACOLOGICAL TREATMENT-INSULIN

Following a positive pregnancy test, patients with preexisting diabetes being treated with insulin or oral antihyperglycemic medications should be transitioned to one of the above options2

1. Castorino K, Jovanovic L. Clin Chem. 2011;57(2):221-30.2. Kitzmiller JL, et al. Diabetes Care. 2008;31(5):1060-79.

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PHARMACOLOGICAL TREATMENT-INSULIN

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PHARMACOLOGICAL TREATMENT-INSULIN DOSING

1. Castorino K, Jovanovic L. Clin Chem. 2011;57(2):221-30. 2. Kitzmiller JL, et al. Diabetes Care. 2008;31(5):1060-79.

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CSII: Administration of rapid-acting insulin via insulin pump Safe and reliable method for satisfying basal insulin needs in

pregnant patients with gestational diabetes mellitus (GDM), T2DM, or T1DM1,2

CSII may need to be combined with CGM for optimal glycemic control in T1DM1

Can be used to effectively mimic physiologic insulin secretion2

No significant difference in glycemic control for pregnancy outcomes with CSII versus multiple-dose insulin (MDI) therapy3

Can help address daytime or nocturnal hypoglycemia or a prominent dawn phenomenon4

Insulin aspart and lispro are the standard of care for CSII5

Disadvantages of CSII: Complexity–requires counseling and training Cost Potential for insulin pump failure/user error or infusion site

problems2,4

INSULIN PUMP THERAPY/CONTINUOUS SUBCUTANEOUS INSULIN INFUSION (CSII)

1. AACE. Endocr Pract. 2011;17(2):1-53. 2. Castorino K et al. Curr Diab Rep, 2012;12:53-59.3. Hod M. Jovanovic L. Int J Clin Pract, 2010;64(166):47-52. 4. Kitzmiller JL, et al. Diabetes Care. 2008;31(5):1060-79.

5. Castorino K, Jovanovic L. Clin Chem. 2011;57(2):221-30.

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TREATMENT

56

Diagnosis of and management procedures for pregnant women complicated with carbohydrate

intolerance

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MANAGEMENT DURING LABOR & DELIVERYTiming and mode of delivery In the case of a GDM patient undergoing insulin

therapy where fetal development is thought to be within the normal range, there is no difference in the caesarean section rate between women for whom labor is induced at 38 weeks and those for whom labor is not induced.

Moreover, it has also been reported that there is no difference in the incidence of macrosomia or caesarean section between insulin-treated GDM patients for whom labor is induced at 38–39 weeks and insulin-treated GDM patients who electively waited for labor and childbirth to take their natural course.

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MANAGEMENT DURING LABOR & DELIVERYTiming and mode of delivery… In the case that the GDM patient has good blood

glucose control and fetal development is thought to be within the normal range, as a general rule it is considered that the pregnancies of GDM patients may be managed in the same manner as those of normal glucose-tolerant women.

In the case that birth weight is estimated at 4,000g or higher, an elective caesarean section is considered.

However, in the case that the patient has poor blood glucose control, induced delivery at 38 weeks onward is considered.

Landon MB, Spong CY, Thom E, et al. A multicenter, randomized trial of treatment for mild gestational diabetes. N Engl J Med. 2009;361:1339–1348.

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MANAGEMENT DURING LABOR & DELIVERYInsulin therapy during labor & delivery:

When carrying out insulin therapy, special care is needed as the amount of insulin required during pregnancy, during delivery, and after birth differs tremendously.

Thus, insulin requirements at the end of pregnancy increase by approximately two-fold.

During first-stage labor the required amount decreases, while in second-stage labor it increases slightly and after birth decreases rapidly.

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MANAGEMENT DURING LABOR & DELIVERYInsulin therapy during labor & delivery…

Accordingly, attention needs to be paid to such changes in required insulin amounts during pregnancy and the amount of insulin administered reduces by half following delivery.

In particular, since it becomes difficult for the patient to eat during first- and second-stage labor, especially careful management of blood glucose levels is necessary in the case that labor and delivery are prolonged

Landon MB, Spong CY, Thom E, et al. A multicenter, randomized trial of treatment for mild gestational diabetes. N Engl J Med. 2009;361:1339–1348.

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MANAGEMENT DURING LABOR & DELIVERYInsulin therapy during labor & delivery…

At the onset of labor the patient is administered an electrolyte fluid containing 5% glucose at a rate of 100–120ml/hr, then administered insulin intravenously via an infusion pump.

Depending on the individual case, blood glucose is measured at intervals of 1–2 hours.

Insulin administration begins with a dosage of 0.5 units/hr and the insulin dosing rate is determined based on fluctuations in blood glucose levels.

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TAKE HOME MESSAGE

Diagnosis of GDM with 75-g oral glucose load Fasting ≥ 92mg/dl; 1hr ≥180mg/dl; 2hr ≥153mg/dl.

Metformin and Glyburide can be used but ADA does not recommend it, ADA recommends Insulin.

Glucose levels for insulin initiation in GDM when non-pharmacological measures fails. Fasting <105mg/dl; 1hr ≤155mg/dl; 2hr ≤130mg/dl.

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