diabetes in pregnancy dr.pasham sharath chandra

DR.P.SHARATH CHANDRA POST GRADUATE

DR.K.SANJEEVIPROFESSOR

DR.P.GANDIAH H.O.D

DEPARTMENT OF MEDICINES.V.S.M.C

Diabetes in pregnancy

Diabetes mellitus

A metabolic condition characterized by chronic hyperglycemia as a result of defective insulin secretion, insulin action or both. Type I (IDDM) Type II (NIDDM) Gestational diabetes Others

Genetic mutations of β-cell function—MODY

Genetic defects in insulin action Genetic syndromes—Down, Klinefelter,

Turner Diseases of the exocrine pancreas—

pancreatitis, cystic fibrosis Endocrinopathies—Cushing syndrome,

pheochromocytoma Drug or chemical induced—

glucocorticosteroids, thiazides, β-adrenergic agonists

Infections—congenital rubella, cytomegalovirus, coxsackievirus


Pregnancy predisposes to persistent hyperglycaemia due to ↑ placental hormones ↑ plasma cortisol A state of insulin resistance Further aggravated by ↑body weight and

↑ caloric intake during pregnancy


Women with diabetes during pregnancy can be divided into 1. Pregestational / Overt

diabetes.2. Gestational diabetes.

African American, Native American, Asian, and Hispanic women are at higher risk for gestational diabetes compared with other races.

The increasing incidence of gestational diabetes during the past 15 years is due to similar statistics for obesity.


Common medical complication of pregnancy.Diabetes in pregnancy is associated with

risks to the woman and to the developing fetus.

Miscarriage, pre-eclampsia, preterm labour and congenital malformations in fetus are more common in women with pre-existing diabetes

White classification in pregnancy

Pregestational / overt diabetes

Diabetes that antedates pregnancy is called pregestational or overt diabetes.

Because of differences in age specific incidences of the two types of diabetes in relation to childbearing years, most of the patients with overt diabetes have type I diabetes.

There is an increasing prevalance of pregestational type II diabetes and can be attributed to Increasing prevalance of obesity and Type II DM in the

young Delayed childbearing into the 3rd and 4th decades.

Pregestational / overt diabetes

Pregnancies complicated by overt diabetes (TypeI/typeII) carry additional risk to both mother and the fetus

Metabolic derangements are present right from the time of conception, during blastogenesis and embryogenesis increase the risk of spontaneous abortions and congenital malformations.

The presence of placental vasculopathy in patients of diabetes severely affects the flow of blood and other substrates to the fetus.

According to ADA IADPSG

1. Random plasma glucose >200mg/dl along with classic signs like polyuria, polydypsia and unexplained weight loss.

2. Fasting plasma glucose levels >125mg/dl

1. Random plasma glucose of atleast 200mg/dl plus other signs.

2. Fasting plasma glucose of atleast 126 mg/dl

3. HbA1c of atleast 6.5%

Diagnosis of overt diabetes

Effect of pregnancy on diabetes

• Increase requirement for insulin doses• Nephropathy , autonomic neuropathy may

deteriorate• Progress in diabetic retinopathy (2X)• Hypoglycemia• Diabetic ketoacidosis

Impact of overt diabetes on pregnancy

The likelihood of successful outcomes with overt diabetes is related somewhat to the degree of glycemic control, but more importantly, to the degree of underlying cardiovascular or renal disease.

Thus, advancing stages of the White classification, are inversely related to favourable pregnancy outcomes.

Effects on the fetus

Spontaneous abortions Risk of abortions is directly related to glycemic

control and HbA1c levels.Pre-term deliveryMalformations

4x increased risk of isolated cardiac defects and 2x increased risk of non cardiac defects

Risk of abortions is directly related to glycemic control and HbA1c levels.

Due to hyperglycemia induced oxidative stress and increased apoptosis


Altered fetal growth Growth may be diminished due to malformations and substrate

deprivations due to placental insufficiency Fetal overgrowth(macrosomia) is a more common and is due to

maternal hyperglycemia and fetal hyperinsulinemia. Raised HC/AC ratios, Increased risk of shoulder dystocia or

cesarean delivery. Unexplained fetal deaths

3-4x higher risk of fetal death, typically without an identifiable cause.

7x higher in women with hypertension with overt diabetes. The infants are typically LGA and die before labour usually

after 35weeks of gestation. Due to poor glycemic control and fetal lactic acidosis.


Hydramnios May be due to fetal polyuria Raised amniotic fluid glucose levels Women with poor HbA1c levels in third trimester are

more likely to have hydramnios.Hypoglycemia

Rapid drop of blood glucose post delivery Due to fetal beta cell hyperplasia induced by chronic

maternal hyperglycemia. Strict maternal glycemic control reduces the risk of

fetal hypoglycemia.


Polycythemia and hyperbilirubinemia Increased EPO levels due to fetal hypoxia and IGF May lead to renal vein thrombosis. Polycythemia leads to increased bilirubun load.

Hypertrophic Cardiomyopathy Mostly affects the interventricular septum and

ventricular wall. In most of the affected, it resolves after delivery.

HypocalcemiaCognitive impairment Inheritance of diabetes

Maternal effects

Diabetes in pregnancy cause serious effects on maternal welfare.

Maternal death is uncommon, but rates in women with diabetes are still increased.

Deaths resulted from diabetic ketoacidosis, hypoglycemia, hypertension, and infection.

Especially morbid is ischemic heart disease and in few studies, only half of the women with coronary artery disease survived pregnancy.

Maternal effects

The incidence of chronic and gestational hypertension and especially preeclampsia is remarkably increased in diabetic mothers.

Diabetics with coexistent chronic hypertension were almost 12 times more likely to develop preeclampsia.

Maternal effects

Diabetic nephropathy Diabetes is a leading cause of ESRD Microalbuminuria, macroalbuminuria, hypertension.

Diabetic retinopathy Retinal vasculopathy is a highly specific complication of

diabetes. Nonproliferative retinopathy: Microaneurysms, blot

hemorrhages, hard exudates. Preproliferative retinopathy: Retinal ischemia and

infarctions that appear as cotton wool exudates. Proliferative retinopathy: In response to ischemia, there is

neovascularization on the retinal surface and out into the vitreous cavity.

Neovascularisation

Maternal effects

Diabetic neuropathy Peripheral neuropathy is uncommon in pregnant

women but diabetic gastroparesis is very troublesome. It causes nausea and vomiting, nutritional problems,

and difficulty with glucose control. Metoclopramide and H2-receptor

antagonists(ranitidine) may help.

Maternal effects

Diabetic ketoacidosis Develops in ~1% of diabetic pregnancies. Pregnant women usually develop ketoacidosis at

lower blood glucose thresholds than when nonpregnant.

Diabetic ketoacidosis (DKA) may develop with hyperemesis gravidarum, β-mimetic drugs given for tocolysis, infection, and corticosteroids given to induce fetal lung maturation.

The incidence of fetal loss can be as high as 20 percent with DKA

Maternal effects

Infections: Almost all types of infections are increased in diabetic

pregnancies. Almost 80 percent of women with type 1 diabetes

develop at least one infection during pregnancy compared with only 25 percent in those without diabetes.

Common infections include Candida vulvovaginitis Urinary and respiratory tract infections, Puerperal pelvic sepsis.

Pregestational diabetes is associated with a two- to threefold increase in wound complications after cesarean delivery.

DIABETES THAT ANTEDATES PREGNANCY

Management of overt diabetes

Management of Diabetes in Pregnancy

Because of the relationship between pregnancy complications and maternal glycemic control,glucose targets should be aggresively achieved during pregnancy.

Management preferably should begin before pregnancy and include specific goals during each trimester.


Preconception councelling: Should be educated about achieving good glycemic

control before conception. Guidance in achieving preconception management

goals. Daily folic acid supplementation to reduce the risk of

neural tube defects. Nutritional councelling with provision of diet plans. Pre-conception goals include (ADA)

1. Fasting and pre-meal glucose levels of 80-110 mg/dl2. 2hr post prandial glucose 100-129mg/dl3. HbA1c <7%4. Avoid hypoglycemia.


Preconceptional councelling: Maternal and fetal risk assesment

Fundoscopy Assesment of renal function

Serum creatnine Spot urinary microalbumin:creatnine ratio Protein:creatnine ratio

Cardiac evaluation by ECG, TMT if >35yrs old Co-existing hypertension/dyslypidemia/CAD/family history/smoking/renal

disease.

ACEI’s and ARB’s should be stopped and shifted to alpha-methyldopa/hydralazine/CCB/Beta-blockers.

All cholesterol lowering agents and statins are contraindicated in pregnancy and should be discontinued before conception.


The following practical self-management skills are essential for attaining good glycemic control in the preparation for pregnancy and during pregnancy:1. Use of appropriate meal plan2. Self-monitoring of blood glucose3. Self-administration of insulin and adjustment of insulin

doses

4. Treatment of hypoglycemia (patient and family members)

5. 5. Incorporate safe physical activity6. Development of techniques to reduce stress.

The same is applicable in women with gestational diabetes also.


DietNutritional planning includes appropriate weight gain

through carbohydrate and caloric modifications based on height, weight, and degree of glucose intolerance.

The mix of carbohydrate, protein, and fat is adjusted to meet the metabolic goals.

175-g minimum of carbohydrate per day divided into three meals and 2-4 snacks is to be taken.

An ideal dietary composition is 55 percent carbohydrate, 20 percent protein, and 25 percent fat, of which < 10 percent is saturated fat.

Weight loss is not recommended, but modest caloric restriction may be appropriate for overweight or obese women


Insulin therapy: The overtly diabetic pregnant woman is best treated with insulin.

Oral hypoglycemic agents are not currently recommended for overt diabetes.(ACOG)

Maternal glycemic control can usually be achieved with multiple daily insulin injections and adjustment of dietary intake.

Insulin therapy

Insulin strategies

Self monitoring of blood glucose is a critical step for insulin therapy and must be done atleast 4 times a day.

Adjusting insulin doses is simpler with self-monitoring of blood glucose (SMBG) 4 times a day because each component of the insulin regimen affects only 1 SMBG value.

Monitoring before meals and 2 h after a meal and before driving is recommended.

Insulin strategies

In overt type I diabetes women, the requirement of insulin may fall during the first trimester due to increased insulin sensitivity but requirements increase in the latter half due to increased circulating placental hormones.

The insulin dose is increased from 0.7 U/kg/day in the first trimester to 0.8 U/kg/day at week 18, 0.9 U/kg/day at week 26,and 1.0 U/kg/day at week 36 in women who maintained within15% of ideal body weight.

Insulin strategies

Insulin strategies

During the first trimester, there is no difference in insulin requirement between type 1 and type 2 subjects.

But type 2 DM patients require a significantly higher dose of insulin during 2nd trimester(33%increase compared to 10% for type I DM) and in 3rd trimester requirement may be raised upto 40%.

This is attributed to the sudden increase in body mass and heightened insulin resistance in type 2 diabetes women during pregnancy.

The total daily dose may reach upto 200units/day but main cocern should be good glycemic control.

Insulin strategies

Insulin strategies

Increased insulin requirement is inevitable in pregnant women with type 2 DM and if not increased in spite of the advancing pregnancy in certain cases, it is a cause of concern.

This could be due to poor placental growth, intrauterine growth retardation, and impending intrauterine death and proactive identification of the cause is needed.

In some cases, fetal beta-cell hypertrophy can handle the maternal glucose levels and may require less insulin.

At 36 weeks, placental growth ceases and counter regulatory hormone production plateaus and there may be an apparent decline in the insulin requirement.

Insulin strategies

Controlling the fasting plasma glucose concentration requires pre-dinner or bedtime NPH insulin.

Pre-dinner administration of NPH insulin, especially if the dose of NPH is increased in view of the next morning’s elevated fasting glucose value, has the likelihood of producing nocturnal hypoglycemia due to the peak pharmacodynamic action of the intermediate acting insulin at midnight. This cannot be prevented even if the patient consumes a bedtime snack.

Alternative strategy to address nocturnal hypoglycemia is to shift the pre dinner NPH insulin to bedtime so that the peak action occurs early in the morning instead of midnight.

Insulin strategies

Injecting NPH in the morning limits patient’s flexibility with regard to meal time and exercise patterns as it exerts its effects for many hours.

Using 3 injections of regular human insulin or rapid acting insulin analogs (Humalog/NovoRapid) with each meal gives a patient more flexibility with regard to eating and exercise.

In a few pregnant women, a split/mixed regimen (NPH and regular or insulin analogs) given in the morning and evening may achieve good glycemic control.

Preprandial regular or rapid-acting insulin analogs can be particularly helpful during the first trimester, when nausea and anorexia (morning sickness) are common.

Management of diabetes in pregnancy

Second trimesterThe glycemic status in the 2nd trimester is more

stable compared to 1st trimester but insulin requirement is increased.

Euglycemia with self-monitoring continues to be the goal in management.

Fetal echocardiography to screen for congenital cardiac malformations.

Maternal serum alpha-fetoprotein determination at 16-20 weeks with targeted sonogram at 18-20 weeks to detect neural-tube defects.


Third trimesterIn view of the threat of late-pregnancy fetal death in

women with diabetes, ACOG recommends various fetal surveillance testing at 32-34 weeks. They include Fetal movement count Periodic fetal heart rate monitoring Intermittent bio-physical profile Contraction stress testing

Mothers are instructed to perform fetal kick counts early in the 3rd trimester.

At 34weeks all insulin treated mothers are preferrably admitted and daily fetal movement counts and FHR monitoring is done thrice a week.

Delivery is planned at 38weeks.


LaborLabor induction may be attempted when the fetus is

not excessively large and the cervix is considered favorable.

Cesarean delivery at or near term has frequently been used to avoid traumatic birth of a large infant, in women with more advanced diabetes, especially those with vascular disease.

The cesarean delivery rate for women with overt diabetes has remained at approximately 80 percent for the past 35 years at a study hospital.


Insulin management during labor1. Usual dose of intermediate-acting insulin is given at bedtime.2. Morning dose of insulin is withheld.3. Intravenous infusion of normal saline is begun.4. Once active labor begins or glucose levels decrease to < 70

mg/dL, change from saline to 5-percent dextrose and deliver at a rate of 100–150 mL/hr to achieve a glucose level of approximately 100 mg/dL

5. Glucose levels are checked hourly using a bedside meter allowing for adjustment in the insulin or glucose infusion rate.

6. Regular (short-acting) insulin is administered by intravenous infusion at a rate of 1.25 U/hr if glucose levels exceed 100 mg/dL.


Purperiumwomen may require virtually no insulin for

the first 24 hours of postpartum.Infection must be promptly detected and

treated.Effective contraception is especially

important in women with overt diabetes to allow optimal glucose control before subsequent conceptions.

RELATIVE INSULIN DEFICIENCY

Gestational diabetes mellitus

Diagnosis

Gestational diabetes is defined as carbohydrate intollerance of any degree with onset (or) first recognition during pregnancy.

It includes diabetes that antedates conception but remained unrecognised untill pregnancy.

It is important to identify GDM in view of the associated fetomaternal risks such as LGA, macrosomia, birth trauma and fetal demise.

More than half of women with gestational diabetes ultimately develop overt diabetes in the ensuing 20 years.

Diagnosis

Different guidelines by the ACOG and the ADA.ACOG recommends a two step diagnostic approach.The recommended two-step approach begins with

either universal or risk-based selective screening using a 50-g, 1-hour oral glucose challenge test followed by a diagnostic 100gm 3hr OGTT.

For the 50-g screen, the plasma glucose level is measured 1 hour after a 50-g oral glucose load without regard to the time of day or time of last meal

Screen is positive if values lie between 135-140mg/dl.

Diagnosis

Maternal and Fetal Effects

The adverse effects of GDM differ from that of overt diabetes.

Unlike in women with overt diabetes, rates of fetal anomalies do not appear to be substantially increased.

But rates of unexplained stillbirths are similar as in women with overt diabetes.

The ADA concluded that fasting hyperglycemia > 105 mg/dL may be associated with an increased risk of fetal death during the final 4 to 8 weeks.

Maternal and Fetal Effects

Fetal macrosomiaNeonatal hypoglycemiaMaternal obesity

Management of gestational diabetes

Women with gestational diabetes can be divided into two functional classes using fasting glucose levels.1. Medical nutrition therapy2. Pharmacological therapy

Medical nutrition therapy

Diet: The aim of meal plan is to provide sufficient calories to sustain adequate nutrition for the mother and fetus and excess weight gain and postprandial hyperglycemia are avoided.

women are advised to divide their calorie consumption, especially the breakfast by splitting the usual breakfast into 2 equal halves and consuming the portions with an interval of 2 h between meals to avoid the undue peak in plasma glucose levels after ingestion of the total quantity of breakfast at one time.

The ACOG recommends a moderate exercise program as part of the treatment plan for women with gestational diabetes.


Glucose monitoring: In a study, women with diet-treated gestational diabetes who used personal glucose monitors had significantly fewer macrosomic infants and gained less weight after diagnosis than women evaluated during clinic visits only.

The ACOG recommends four-times daily glucose monitoring performed fasting and either 1 or 2 hours after each meal.


Oral hypoglycemic agentsSeveral studies proved the safety and efficacy of

gliburide and metformin in the management of gestational diabetes with results on par with insulin but gliburide failed to control if FBS is >110mg/dl.

Metformin treatment for polycystic ovarian disease throughout pregnancy reduced the incidence of gestational diabetes.

Both gliburide and metformin cross the placenta but have no adverse effects on the perinatal outcome.

Use of OHA’s for treating GDM donot cause an increase in adverse effects but may require supplemental insulin for better control.


Insulin is essential if diet control and exercise fail to achieve euglycemia.

Insulin doesnot cross the placenta and tight glycemic control can be achieved.

The ACOG also recommends that insulin be considered in women with Fasting levels persistantly exceed 95mg/dl 1-hour postprandial levels that persistently exceed

140 mg/dL 2-hour levels above 120 mg/dL


The initial dose of NPH insulin could be as low as 4 units and the dose of insulin can be adjusted on follow up.

A few GDM patients may require combination of short-acting insulin and intermediate-acting insulin in the morning and evening.

If a patient has elevated prelunch blood sugar, regular insulin is usually necessary in the morning to handle the post-breakfast hyperglycemia, as there is a lag period before the intermediate-acting insulin begins to work. The above regimen of regular and intermediateacting insulin in the morning controls hyperglycemia


If the post-dinner blood sugar is high, a small dose of regular insulin is necessary before dinner in addition to the regular and intermediate acting insulin given in the morning.

Combination of regular- and intermediate-acting insulin before dinner may be necessary if fasting blood sugar is high.

This combination of short- and intermediate- acting insulin in the morning and in the evening is known as split-mixed dosage regimen. In this regimen two-thirds of the total daily dose of insulin is given in the morning and one-third in the evening.For each combination, one-third dose should be regular insulin and two-thirds should be intermediate-acting insulin.

With this regimen, if the patient continues to have fasting hyperglycemia, the intermediate-acting insulin has to be given at bedtime instead of pre-dinner insulin and the dose has to be adjusted.

Target is to obtain mean fasting levels of 105mg/dl and mean postprandial values of 120mg/dl for better perinatal outcome.


Obstetrical managementFor women with gestational diabetes who do

not require insulin, early delivery or other interventions are seldom required.

The ACOG recommends fetal surveillance in women with gestational diabetes and poor glycemic control.

Insulin-treated women are offered inpatient admission after 34 weeks’ gestation, and fetal heart rate monitoring is performed three times each week.


Women with gestational diabetes and adequate glycemic control are managed expectantly

Elective induction of labor to prevent shoulder dystocia may be done.

Elective cesarean delivery should be done if fetal weight is atleast 4500gms. To avoid brachial plexus injury.


Postpartum evaluation50% of the women with GDM may develop

overt diabetes within 20years.Women diagnosed with gestational diabetes

should undergo evaluation with a 75-g oral glucose tolerance test at 6 to 12 weeks postpartum and atleast every 3yrs thereafter.

Recurrent GDM: 40% of women with GDM tend to develop it again in subsequent pregnancies and obese women have a greater propensity.

Post partum evaluation

REFERENCESJOSLIN’S 14 T H ED.

JAPI VOL:59WILSON,S OBSTETRICS24TH ED.

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diabetes in pregnancy dr.pasham sharath chandra

Health & Medicine