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DIABETES MELLITUS

DR. DAYRES RELLIQUETE

Etiological Classification of Diabetes Mellitus


Type 1:
-cell destruction, usually absolute insulin deficiency, immunemediated, idiopathic
Type 2:
Ranges from predominantly insulin resistance to predominantly
an insulin defect with insulin resistance
Other types:
Drug or chemical induced: glucocorticosteroids,
thiazides, -adrenergic agonists, others
Infections: congenital rubella, cytomegalovirus,
coxsackievirus
Gestational diabetes
*MODY: maturity-onset diabetes of the young
Genetic mutations of -cell function: MODY 1-6, others
Genetic defects in insulin actin
Genetic syndromes: Down, Klinefelter, Turner
Diseases of the exocrine pancreas: pancreatitis, cystic
fibrosis
Endocrinopathies: Cushing syndrome,
pheochromocytoma, others

Proposed Classification System for Diabetes in Pregnancy


Gestational diabetes: diabetes diagnosed during pregnancy that
is not clearly overt (type 1 or type 2) diabetes
Type 1 Diabetes:
Diabetes resulting from -cell destruction, usually leading to
absolute insulin deficiency
a. Without vascular complications
b. With vascular complications (specify which)
Type 2 diabetes:
Diabetes from inadequate insulin secretion in the face of
increased insulin resistance
a. Without vascular complications
b. With vascular complications (specify which)
Other types of diabetes: genetic in origin, associated with
pancreatic disease, drug-induced, or chemically induced

Pregestational Diabetes
Many women found to have gestational diabetes are likely to
have type 2 diabetes that has previously gone undiagnosed
5-10% of women with gestational diabetes are found to have
diabetes immediately after pregnancy

Diagnosis
High plasma glucose levels, glucosuria, and ketoacidosis
Random plasma glucose leve > 200 mg/dL
Classic signs and symptoms: polydipsia, polyuria, and
unexplained weight loss
Fasting glucose level exceeding 125 mg/dL
Diagnosis of Overt Diabetes in Pregnancy
Measure of glycemia
Threshold
Fasting plasma glucose
At least 7.0 mmol/L
(126 mg/dL)
Hemogblobin A1c

At least 6.5%

Random plasma glucose

At least 11.1 mmol/L


(200 mg/dL)

*women without known diabetes antedating pregnancy


Risk factors for impaired carbohydrate metabolism in pregnant
women
Strong family history of diabetes
Prior delivery of large newborn
Persistent glucosuria
Unexplained fetal losses
Impact on pregnancy-fetal effects
Spontaneous abortion
Preprandial glucose concentrations >120 mg/dL
Glycohemoglobin A1c
concentrations >7% 3x abortion rate
Preterm delivery (increased 5x)
Overt diabetes is an undisputed risk factor
Babies affected malformations (Norway)
Cardiovascular
Musculoskeletal
(caudal regression)
Gastrointestinal
CNS
Urogenital
Chromosomal
Multiorgan
Others

Altered fetal growth


Diminished growth results from congenital malformations or
from substrate deprivation due to advanced maternal vascular
disease
Fetal overgrowth is more typical of pre-gestational diabetes
Maternal hyperglycemia fetal hyperinsulinemia excessive
somatic growth or macrosomia

Unexplained fetal demise


Fetal death is 3-4X higher in women with type 1 diabetes
compared with that of the general obstetrical population

Cardiomyopathy
Hypertrophic cardiomyopathy that primarily affects the
interventricular septum in severe case

Stillbirth without an identifiable cause is a phenomenon


relatively limited to pregnancies complicated by overt diabetes

Obstructive cardiac failure

These infants are typically LGA and die before labor, usually
after 35 weeks gestation or later

Long-term cognitive development


Intelligence quotient of those whose mothers had diabetes
during pregnancy averaged 1 to 2 points lower demonstrated
impaired memory performance

Hydramnios
Diabetic pregnancies are often complicated by excess amnionic
fluid:
amnionic fluid index (AFI) > 24 cm in the 3rd trimester

Autism spectrum disorders or development delay were more


common in children of diabetic women
Link between maternal diabetes, glycemic control, and
neurocognitive outcome

Neonatal effects
Increased frequency of preterm delivery in women diabetes due
to advanced diabetes with superimposed pre-eclampsia

Respiratory Distress Syndrome


Gestational age rather than overt diabetes is likely the most
significant factor associated with respiratory distress syndrome

Inheritance of Diabetes
Risk of developing type 1 diabetes if either parents is affected is
3-4%
Type 2 diabetes has much stronger genetic component. If both
parents have type 2 diabetes, the risk of developing it
approaches 40%

Hypoglycemia
Newborns of a diabetic mother experience a rapid drop in
plasma glucose concentration after delivery

Older maternal age and maternal type 1 diabetes are important


risk factors

Hyperplasia of the fetal -islet cells induced by chronic maternal


hyperglycemia

Pre-eclampsia
Hypertension that is induced or exacerbated by pregnancy is the
complication that most often forces preterm delivery in diabetic
women.

Low glucose concentrations defined as <45 mg/dL are


particularly common in newborns of women with unstable
glucose concentrations during labor

Pre-eclampsia developed 3-4X more often in women with overt


diabetes

Hypocalcemia
Total serum calcium concentration <8 mg/dL in term newborns

Moreover, those diabetics with coexistent chronic hypertension


were almost 12X more likely to develop preeclampsia

Aberrations in magnesium-calcium economy, asphyxia, and


preterm birth

The National Institute for Health and Clinical Excellence (2008)


established guidelines recommending that pregnant women
with pre-existing diabetes should routinely be offered retinal
assessment after the first prenatal visit

Hyperbilirubinemia and Polycythemia


Major contributing factor is newborn polycythemia, which
increase the bilirubin load

Currently, most agree that laser photocoagulation and good


glycemic control during pregnancy minimize the potential for
deleterious effects of pregnancy.

Polycythemia is thought to be a fetal response to relative


hypoxia
Fetal hypoxia are hyperglycemia-mediated increases in maternal
affinity for oxygen and fetal oxygen consumption
Together with insulin-like growth factors, this hypoxia leads to
increased fetal erythropoietin levels and red cell production

Diabetic neuropathy
Peripheral symmetrical sensorimotor diabetic neuropathy is
uncommon in pregnant women

Diabetic gastropathy is troublesome during pregnancy. It causes


nausea and vomiting, nutritional problems, and difficulty with
glucose control
Gastroparesis is associated with a high risk of morbidity and
poor perinatal outcome
Treatment with metoclopramide and H2-receptor antagonists is
sometimes successful

Diabetic ketoacidosis (DKA)


Diabetic ketoacidosis (DKA) may develop with hyperemesis
gravidarum, -mimetic drugs given for tocolysis, infection, and
corticosteroids given to induce fetal lung maturation
DKA results from an insulin deficiency combined with an excess
in counter-regulatory hormones such as glucagon. This leads to
gluconeogenesis and ketone body formation
The ketone body -hydroxybutyrate is synthesized at a much
greater rate than acetoacetate, which is preferentially detected
by commonly used ketosis detection methodologies, serum or
plasma assays for -hydroxybutyrate more accurately reflect
true ketone body levels.
The incidence of fetal loss can be as high as 20% with DKA
Noncompliance is a prominent factor, and this and ketoacidosis
were historically considered prognostically bad signs in
pregnancy
Pregnant women usually develop ketoacidosis at lower blood
glucose thresholds than when non-pregnant.

Protocol Recommended by ACOG (2012)


Management of DKA during pregnancy
Laboratory assessment
Obtain arterial blood gases to document degree of acidosis
present, measure glucose, ketones, and electrolyte levels at 1to 2-hour interval
Insulin low-dose, IV:
Loading dose: 0.2-0.4 U/kg
Maintenance: 2-10 U/h
Fluids:

Isotonic NaCl
Total replacement in 1st 12 hours of 4-6 L
1 L in 1st hour
500-1000 mL/h for 2-4 hours
250 mL/h until 80% replaced

Glucose:
Begin D5NS when glucose plasma level reaches
250mg/dL (14 mmol/L)

Potassium
If initially normal or reduced, an infusion rate up to 1520 mEq/h may be required; if elevated, wait until levels
decrease into the normal range, then add to IV solution
a concentration of 20-30 mEq/L
Bicarbonate
Add one ampule (44 mEq) to 1 L of 0.45 NS if pH <7.
Infections
Almost 80% of women with type 1 diabetes develop at
least 1 infection during pregnancy compared with only
25% in those without diabetes
Common infections include Candidia vulvovaginitis,
urinary and respiratory tract infections, and puerperal
pelvic sepsis

Self-monitored Capillary Blood Glucose Goals


Specimen
Fasting
Pre-meal
1-hr postprandial
2-hr postprandial
0200-0600
Mean
HbA1c

Level, mg/dL
95
100
140
120
60
100
6%

Ideal dietary composition


55% carbohydrate
20% protein
25% fat ( <10% is saturated fat)

Second trimester
Maternal serum -fetoprotein determination at 16-20 weeks
gestation is used in association with targeted sonographic
examination at 18-20 weeks to detect neural-tube defects and
other anomalies.
Maternal -fetoprotein levels may be lower in diabetic
pregnancies, and interpretation is altered accordingly.
Because the incidence of congenital cardiac anomalies is 5X
greater in mothers with diabetes, fetal echocardiography is
important.

Third trimester and Delivery


Recommendations for various fetal surveillance programs
beginning in the 3rd trimester:
Fetal movement counting
Periodic fetal heart rate monitoring
Intermittent biophysical profile evaluation and
contraction stress testing

None of these techniques has been subjected to


prospective randomized clinical trials, and their primary
value seems related to their low false-negative rates
The ACOG (2012) suggests initiating such testing at 32-34 weeks
gestation.
Delivery is planned for 38 weeks
Labor 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 a woman with diabetes

Puerperium
Often, women may require no insulin for the first 24 hours
postpartum
Subsequently, insulin requirements fluctuate next few days
Infection must be promptly detected and treated
Carbohydrate intolerance of variable severity with first
recognition during pregnancy

1-step procedure: diagnostic 100-g OGTT perform


on all subjects

High Risk
Perform blood glucose testing as soon as feasible, using the
procedures described above, if one or more of these present:
Severe obesity
Strong family history of type 2 diabetes
Previous history of GDM, impaired glucose metabolism,
or glucosuria
If GDM is not diagnosed, blood glucose testing should be
repeated at 24-28 weeks gestation or at any time symptoms or
signs suggest hyperglycemia
Consensus development conference in 2013 concluded that
evidence is insufficient to adopt a 1-step approach
The recommended 2-step approach begins with either universal
or risk-based selective screening using a 50-g, 1-h oral glucose
challenge test
Screening should be performed between 24 and 28 weeks
gestation in those women not known to have glucose
intolerance earlier in pregnancy

Applies whether or not insulin is used for treatment and


includes women with unrecognized diabetes

This 50-g screening test is followed by a diagnostic 100-g 3-hour


oral glucose tolerance test (OGTT) if screening results meets or
exceed a predetermined plasma glucose concentration.

5th International Workshop-Conference On Gestational


Diabetes: Screening Strategy Based On Risk
Assessment for Detecting GDM

US Preventive Service Task Force (2013) recommends universal


screening:
Low-risk women after 24 weeks gestation

GDM risk assessment: ascertained at first prenatal


Low risk
Blood glucose testing not routinely required if all of the
following are present:
Member of an ethnic group with a low prevalence
of GDM
No known diabetes in 1st-degree relatives
Age<25 years
Weight normal before pregnancy
Weight normal at birth
No history of abnormal glucose metabolism
No history of poor obstetrical outcome
GDM risk assessment: ascertained at first prenatal
Moderate Risk:
Perform blood glucose testing at 24-28 weeks either:
2-step procedure:
o 50-g PO glucose challenge test, followed by a
diagnostic
o 100-g OGTT for those meeting the threshold
value in the GCT

Maternal and Fetal Effects


Fetal Macrosomia
Primary effect attributed to gestational diabetes is
excessive fetal size or macrosomia
Maternal hyperglycemia prompts fetal
hyperinsulinemia (2nd half of pregnancy) stimulates
excessive somatic growth
Perinatal goal: avoid difficult delivery from macrosomia and
concomitant birth trauma with shoulder dystocia.

Maternal obesity
Maternal BMI is an independent and more substantial risk factor
for fetal macrosomia than is glucose intolerance
Higher BMI levels were associated with increasing birthweight,
regardless of glucose levels.
Maternal obesity is an important confounding factor in the
diagnosis of gestational diabetes

Excessive gestational weight gain is commonly identified in


women with gestational diabetes and also confers an additive
risk for fetal macrosomia.

Management
Women with gestational diabetes can be divided into two
functional classes using fasting glucose levels
Pharmacological methods are usually recommended if diet
modification does not consistently maintain the fasting plasma
glucose

Postpartum evaluation
50% likelihood of women with gestational diabetes developing
overt diabetes within 20 years
*75-g oral dose tolerance test at 6-12 weeks postpartum and
other intervals thereafter
Either a fasting glucose or the 75-g, 2-h OGTT for the diagnosis
of overt diabetes (ACOG 2013)
*ADA (2011) recommends testing at least every 3 years in
women with a history of gestational diabetes but normal
postpartum glucose screening

Level <95 mg/dL or the 2-hour postprandial plasma glucose <


120 mg/dL
Nutritional instructions include a carbohydrate controlled diet
to maintain normoglycemia and avoid ketosis.
On average, this include a daily caloric intake of 30-35 kcal/kg
Moderate exercise program as part of the treatment plan for
women with gestational diabetes (ACOG 2013)
4X daily glucose monitoring performed fasting and either 1 or 2
hours after each meal (ACOD 2013)
*insulin can be considered
1-h postprandial levels persistently >140 mg/Dl OR 2-h levels
>120 mg/dL
If insulin is initiated, the starting dose is typically 0.7-1.0
units/kg/d given in divided doses
Combination of intermediate-acting and short-acting insulin
may be used, and dose adjustments are based on glucose levels
at particular times of the day
Both glyburide and metformin are appropriate, as is insulin, for
1st-line glycemic control in women with gestational diabetes
(ACOG 2013)
Because long-term outcomes have not been studied, the
committee recommends appropriate counseling when
hypoglycemic agents are used.
Cesarean delivery should be considered in women with
gestational diabetes whose fetuses have a sonographically
estimated weight 4500 g (ACOG 2013)

Recurrent Gestational Diabetes


Subsequent pregnancies: recurrence in 40% of 344 primiparous
women with gestational diabetes
Obese women were more likely to have impaired glucose
tolerance in subsequent pregnancies
Lifestyle behavioral change, including weight control and
exercise between pregnancies, likely would prevent gestational
diabetes recurrence
Loss at least 2 BMI units was associated with a lower risk of
gestational diabetes in women who were overweight obese in
the first pregnancy.
Only 4.2% of women without gestational diabetes in their first
pregnancy were diagnosed with gestational diabetes when
screened in a second pregnancy, compared with 41.3% in
women with a history of gestational diabetes.

Contraception
Low-dose hormonal contraception
Rate of subsequent diabetes in oral contraceptive users is not
significantly different from that in those who did not use
hormonal contraception
*importantly, comorbid obesity, hypertensive, or dyslipidemia
should direct the choice for contraception toward a method
without potential cardiovascular consequences. In these
instances, the IUD is a good alternative.