The Primary Care Guide for Pregnancy Diabetes
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Transcript of The Primary Care Guide for Pregnancy Diabetes
For internal use only. This training material is for educational purposes. It is not to be used, shared, or discussed with customers. Proprietary & Confidential ©AstraZeneca 2014
HYPERGLYCEMIA IN PREGNANCY
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What is DM?• A metabolic condition
characterized by chronic hyperglycemia as a result of defective insulin secretion, insulin action or both
• Type 1(IDDM)• Type 2(NIDDM)• Gestational diabetes• Others
– genetic defects in insulin processing or action
– Endocrinopathies– Drugs– exocrine pancreatic defects– genetic syndromes associated with
DM
2
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Pregnancy predisposes to persistent hyperglycaemia
• Glucose is made available to the fetus– ↑ placental hormones– ↑ plasma cortisol– A state of insulin resistance– Further aggravated by ↑ body weight and ↑ caloric
intake during pregnancy• GDM develops when the pancreas cannot overcome
the effect of these hormones• Pregestational diabetes becomes worse during
pregnancy
3
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Diabetes & Pregnancy4
the prevalence of women with preexisting T2DM getting pregnant (diabetic pregnancies) seems to be rising
nowadays, more and more women go into pregnancy with increased body weight and caloric intake
This prevalence is increasing
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• Glucose intolerance of variable severity with onset or first identification during the pregnancy
– Generally occurs in the latter half of pregnancy
– Previously, found to constitute 90% of diabetes in pregnancy
• resolving after delivery
5
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Important facts• To understand the effects of hyperglycaemia on
the fetus, it should be remembered that glucose crosses the placenta freely but maternal insulin does not
• Thus, maternal hyperglycaemia leads to fetal hyperglycaemia with a consequent rise in fetal insulin secretion
• Pregnancy is a state of insulin resistance, especially towards term
6
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WHAT DOES CHRONIC HYPERGLYCAEMIA LEAD TO?
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Multiple implications8
MaternalPre-eclampsiaRecurrent infection-vaginal candidiasis,UTIPolyhydramnios—PPROM, discomfortAnomalies & abortionsSudden IUD
Delivery Problems• Increased instrumental
rates• Birth trauma• Operative delivery• Polyhydramnios—
premature membrane rupture, cord prolapse
Postpartum• Increased risk of developing
DM later in life• Past history of GDM increases
the risk of recurrence in subsequent pregnancies
Retnakaran R. Diabetes Care, 31, 1275-1281
Maternal - medical• Retinopathy• Nephropathy• Neuropathy • Micro/macroangiopathy
FetalCongenital anomalies (4 fold) - sacral agenesis, NTD, cardiac and renal anomaliesMacrosomiaMalpresentationShoulder dystociaPrematurityRespiratory distress syndromeHypoglycemia
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9
Fetal macrosomiaThe child later
on…..• Obesity
• Diabetes
mellitus
• Reproductive
problems
• Metabolic
syndrome
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WHY IS IT IMPORTANT TO DIFFERENTIATE BETWEEN GESTATIONAL & PREGESTATIONAL DM?
because each diagnosis imparts a different clinical significance
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future development of T2DM
The significance of GDM
mothers are at risk of
adverse obstetrical outcomes- esp. fetal overgrowth
11
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growth restriction
The significance of pregestational DM
12
Most of the risk is to the fetus
complications during organogenesis
+ complications similar to GDM
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Pregestational diabetic pregnancies
• carry a graver consequence– should be managed immediately once
identified• Ideally, evaluation for DM should occur
before pregnancy– to prevent complications during organogenesis
(1st trimester)
13
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Hyperglycaemia in the 1st trimester• confers a significantly
increased risk of major malformations
14
Type of Diabetes in pregnancy
T1DM(n=221)
T2DM(n=317)
GDM(n=1822)
Risk of Major congenital abnormality(%)
5.9 4.4 1.4
Farrel T 2002
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Fetal malformations & Glycaemic control
• HAPO study • a continuum of increasing risk of perinatal
outcomes as glucose levels increase– even within levels that were previously defined as
normal
15
HAPO study. NEJM 2008
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Hyperglycaemia later in pregnancy
• High blood glucose increases fetal growth• Postprandial normoglycemia can reduce the rate
of macrosomia
16
HAPO study. NEJM 2008
FBG>5mmol/L, HbA1c>5.3% MACROSOMIA!
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Difference between GDM & DM• GDM
– early pregnancy BS normal
– Usually no effect on organogenesis
– less likely to have congenital defects
– diabetes disappears after delivery
– macrosomia more likely
• DM + Pregnancy– elevated BS since before
pregnancy– effect during
organogenesis– more likely to have
congenital fetal defects (up to 8x more than normal pregnancy)
– fetes may be growth restricted
17
overall though, perinatal outcomes are worse whatever the cause of the hyperglycaemia
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HOW DO WE DETECT THOSE ASYMPTOMATIC MOTHERS WITH DM?
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Issues of concern1. The frequently undiagnosed nature of
T2DM before pregnancy2. Lack of preconception care3. The increase in complications of
pregnancy due to the coexistence of obesity and T2DM
19
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Pregnant women with DM are frequently asymptomatic
• They need to be identified before harm can come to the fetus
20
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Screening• during antenatal check-ups,
mothers with unknown elevations of blood glucose need to be identified
• this process of looking for asymptomatic diabetics is termed screening
• The benefits and importance of screening for GDM have been proven (ACHOIS & HAPO study)
21
Crowther NEJM 2005
elevations of maternal blood glucose are deemed harmful to the fetus
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In Malaysia• we base our screening strategy on
22
screen selectively those considered high risk (1-step
testing)
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Who are those considered high risk?Pregnant women should be screened if they have any of the following risk factors:• BMI > 27kg/m2
• Previous macrosomic baby weighing 4kg or above• Previous gestational diabetes mellitus (GDM)• First-degree relative with diabetes• Bad obstetric history• Glycosuria at the first prenatal visit• Current obstetric problems (essential
hypertension, pregnancy induced hypertension, polyhydramnios and current use of steriods)
• Age above 25 1
23
1. ADA Diabetes Care 20092. Retnakaran R. Clin Endocrinol 2007, Lo JC. Diabetes Care, 20063. Kousta E. Clin Endocrinol, 2000
In recent time, this list has been expanded to include factors such as 2
physical inactivitycertain dietary patternspolycystic ovarian syndrome (PCOS)biochemical markers such as adiponectin & C-reactive protein
Ex-GDM mothers investigated for PCOS- a majority of them displayed characteristic polycystic ovarian morphology
3
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Pregnant women should be screened if they have any of the following risk factors:BMI > 27kg/m
2
Previous macrosomic baby weighing 4kg or abovePrevious gestational diabetes mellitus (GDM)First-degree relative with diabetesBad obstetric historyGlycosuria at the first prenatal visitCurrent obstetric problems (essential hypertension, pregnancy induced hypertension, polyhydramnios and current use of steriods)Age above 25
1
What is done now• At booking - assess risk• if risk present, do OGTT
24
First Obstetric Visit• check risk status
Risk Factors
AbsentPresent
Consider normal
OGTT performed after 24 weeks gestation
Consider GDM if diagnostic criteria met
Note:OGTT not performed in:Known pre-existing DM cases& Cases with P/H of GDM
Current screening protocol
Risk Factors• Age >= 40 yrs• Unexplained SB• P/H recurrent miscarriages• P/H BW >= 4.0 kg• Weight > 100 kg• P/H oligomenorrhoea• Strong maternal sibling F/H
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Schedule for screening• Between 24-28 weeks of gestation • or earlier if there are stronger indications
25
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Recent Recommendations• Based on HAPO study data - even the slightest
hypoglycaemia increases pregnancy adversity
• IADPSG formulated recommendations
• In a bid to achieve international consensus
• Try to catch as many patients with pregnancy hyperglycaemia as possible
26
IADPSG. Diabetes Care 2010
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IADPSG strategy27
*To be applied to women without known diabetes antedating pregnancy. Postpartum glucose testing should be performed for all women diagnosed with overt diabetes during pregnancy or GDM. + Decision to perform blood testing for evaluation of glycemia on all pregnant women or only on women with characteristics indicating a high risk for diabetes is to be made on the basis of the background frequency of abnormal glucose metabolism in the population and on local circumstances. ǂ The panel concluded that there have been insufficient studies performed to know whether there is a benefit of generalized testing to diagnose and treat GDM before the usual window of 24-28 weeks’ gestation.IADPSG. Diabetes Care 2010
Table 2 – Strategy for the detection and diagnosis of hyperglycemic disorders in pregnancy*
First prenatal visitMeasure FPG, A1C, or random plasma glucose on all or only high-risk women+
• If results indicate overt diabetes as per Table 1– Treatment and follow-up as for preexisting diabetes
• If results not diagnostic of overt diabetes– and fasting plasma glucose ≥ 5.1 mmol/l (92 mg/dl) but < 7.0 mmol/l (126 mg/dl), diagnose as GDM– and fasting plasma glucose < 5.1 mmol/l (92 mg/dl), test for GDM from 24 to 28 weeks’ gestation with a 75-g OGTT ǂ
24-28 weeks’ gestation: diagnosis of GDM2-h 75-g OGTT: perform after overnight fast on all women not previously found to have overt diabetes or GDM during testing earlier in this pregnancy• Overt diabetes if fasting plasma glucose ≥ 7.0 mmol/l (126 mg/dl)• GDM if one or more values equals or exceeds thresholds indicated in Table 1• Normal if all values on OGTT less than thresholds indicated in Table 1
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IADPSG screen
• 1st phase - early pregnancy– aimed at detecting previously undiagnosed overt diabetes
– HbA1c or plasma glucose (fasting or random) measurements
– carried out on high-risk women (adult non-pregnant criteria)
• 2nd phase - 24-28 weeks• if 1st phase normal
• 2-hour 75 g OGTT
28
IADPSG. Diabetes Care 2010
2 discrete phases
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THE OGTT
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OGTT• The first-line diagnostic test• Initially developed to identify the diabetic in the
general population
30
O’Sullivan, Mahan. Diabetes 1964.
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Procedure for OGTT31
IADPSG. Diabetes Care 2010
Table 6 – Screening for and diagnosis of GDMPerform a 75-g OGTT, with plasma glucose measurement fasting and at 1 and 2 h, at 24-28 weeks of gestation in women not previously diagnosed with overt diabetes.The OGTT should be performed in the morning after an overnight fast of at least 8 h.The diagnosis of GDM is made when any of the following plasma glucose values are exceeded:• Fasting: ≥ 92 mg/dL (5.1 mmol/L)• 1 h: ≥ 180 mg/dL (10.0 mmol/L)• 2 h: ≥ 153 mg/dL (8.5 mmol/L)
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Diagnostic Values 32
OGTT Plasma Glucose Values (mmol/L)Category 0-hour 2-hourNormal < 6.1 * < 7.8
IFG 6.1 * – 6.9 -IGT - 7.8 – 11.0DM ≥ 7.0 ≥ 11.1
Table 2: Diagnostic values for Type 2 Diabetes Mellitus/Glucose Intolerance – oral glucose tolerance test (OGTT) [IDF 2005]
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More recent diagnostic criteria• Commonly referred to
diagnostic criteria for the 75 gram OGTT include the WHO and the ADA criteria
• More recently, the IADPSG have adopted stringent criteria based on the HAPO study
33
IADPSG. Diabetes Care 2010
75-gram oGTT values WHO ADA* IADPSGFasting blood glucose mmol/
l≥ 7.0 ≥ 5.3 ≥ 5.1
1-hour blood glucose mmol/l ≥ 10.0 ≥ 10.0
2-hour blood glucose mmol/l ≥ 7.8 ≥ 8.6 ≥ 8.5
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Postpartum considerations34
Should be carried out after 2 months postpartum
P/H GDM woman
Postpartum oGTT
Normal GTAbnormal GT
IGT/DM
Diet & exerciseF/U Blood Glucose Manage as
appropriate
Stable glucose Raised glucose
Diet & exerciseF/U Blood Glucose
75g oGTT
Normal GT
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IS THERE ANY OTHER WAY TO DIAGNOSE DM IN PREGNANCY?
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Yes, but…
• Only in early pregnancy• Glycated haemoglobin (HbA1c) and plasma
glucose (random or fasting)• HbA1c has been validated for the diagnosis of
DM outside of pregnancy (≥6.5%) with many authorities favouring its use in pregnancy as well
36
International Expert Committee. Diabetes Care 2009
HbA1c limitations•costs•unavailability• inaccuracy in anaemia
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Plasma glucose
• Fasting or random
• FPG level of ≥7.0 mmol/L is diagnostic of overt diabetes
• RPG of ≥11.1 mmol/L has to be confirmed with either an FPG or A1c value ≥ the threshold
37
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HOW DO WE MANAGE HYPERGLYCAEMIA IN PREGNANCY?
p-
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Strategy• Rapid normalisation of blood glucose
• Limited weight gain
• Monitoring for anomalies and complications
• Avoiding macrosomia
• Planned delivery
39
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Optimization of metabolic control
• BS control dependant upon diet modification, exercise and hypoglycaemic medications
• Lifestyle modification (dietary advice & appropriate exercise) should be the primary interventions considered
• Resort to medications only when these fail to achieve the desired targets
40
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WHAT IS THE DIETARY ADVICE FOR DIABETES IN PREGNANCY?
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Weight gain• Less weight gain is safe and has
a beneficial effect on perinatal outcomes in obese women
• A dietitian can provide individualised counselling
42
Caloric restriction• A 33% reduction of calories results in
clinically relevant improvement in glycemic parameters
• 30-35 kcal/kg/day = 1200 Kcal/d is safe• 50% of these calories should be from
complex carbs• Base calculations on home blood
glucose levels
Specific TargetsAvoid concentrated sweets and highly processed foods -
soft drinks, ice cream, cakes and sweetsrestrict CHO to those found in vegetables and dairy products like cheese and cottage cheese
Small frequent meals (4 hourly) instead of fewer larger meals
reduces the amount of insulin needed at any one time, resulting in lower glucose excursionsalso reduce hunger and prevent overeating
Hone J. J Clin Endocrinol Metab 2010
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Some more targets• Breakfast should be small & low in
carbs because insulin resistance is highest in the morning
• High-fiber and low-GI foods should be substituted wherever possible for simple sugars
• higher fiber/low GI may assist in delaying absorption of food, thus allowing the insulin peak to “catch up”
• Foods rich in antioxidants have a role in reducing the incidence of fetal anomalies
• fruits and vegetables are recommended
43
Folic acid supplementation Proven to reduce the risk of neural tube defectsat least 3 months preconceptionally and through the first trimester Minimum dose of 4 mg daily
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WHAT TO DO IF DIETARY INTERVENTION DOES NOT WORK?
Medication is implemented if 2 or
more glucose values are elevated
after 1 wk of lifestyle management
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Oral medication?
There is enough data to show that oral
hypoglycaemic agents (OHAs) are safe in
pregnancy
45
Glibenclamide - the 1st OHA to have proven efficacy and safety in pregnancy
At a dose of 2.5 mg daily to a maximum of 20 mg per daySimilar birth outcomes can be achieved when comparing glibenclamide use to insulin initiation in pregnancy
Langer et al. N Eng J Med 2000Rowan et al. N Eng J Med 2008
Metformin - start 500 mg OD & increase to 500 mg tds
Similar outcomes between metformin and insulin initialisationAlthough 46% of mothers on metformin required additional insulin supplementation for blood sugar optimisation
Although both metformin and glibenclamide cross the placenta, there have been no reports of fetal
adversity so far
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When to start OHAs?
• When fasting or premeal BS values constantly exceed 5.5 mmol/L
• dose increase every 4-5 days• OHAs should be started without hesitation
whilst encouraging dietary and exercise efforts
46
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WHEN DO WE USE INSULIN?
When MNT & OHA fails to achieve
glycemic goals after 1 wk
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Summary of insulins48
Type of insulin
Generic name
Onset Peak Duration
Rapid-acting Insulin lispro 15 minutes 30-90 minutes 3-5 hoursInsulin aspart
Short-acting Regular insulin 30-60 minutes 2-4 hours 5-8 hoursIntermediate acting NPH insulin 1-3 hours 8 hours 12-16 hours
Long-actingInsulin glargine
1 hour Peakless 20-26 hoursInsulin detemir
Commonly used insulins and their properties
• Each type of insulin has an onset time, a peak and duration of action
• The onset time delineates how soon the blood glucose lowering action comes into effect and is commonly used to classify this class of medications - either rapid-, short-, intermediate- or long-acting
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Development of Insulins49
Insulin Type Description
Regular or Human
1st biosynthetic type short acting, not very effective for postprandial control, tending to cause hypoglycaemia
Insulin analogues (lispro, aspart)
technically not insulins
They act rapidly, peak in about 1 hour with a duration of action between 2-4 hours
NPH insulin intermediate acting may be mixed with shorter acting insulins to complement its actions
Newer insulin analogues
long acting (peakless) 24 hour duration of action - once daily; provide constant glucose lowering effect; less hypoglycaemia & weight gain
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HOW DO WE CALCULATE THE AMOUNT OF INSULIN TO USE?
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Philosophy behind insulin• Mimic physiologic secretion of insulin as
close as possible• In pregnancy, this entails multiple injections
of various combinations of rapid, short and intermediate-acting insulin
51
A tried and tested insulin combination is a rapid-acting and
NPH one
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Starting dose calculation52
Jovanovic. Diab Care 1982Lapolla et al. Diab Med 2009
Time of pregnancy DosePrepregnancy 0.6 U/kg/dayFirst trimester 0.7 U/kg/daySecond trimester 0.8 U/kg/dayThird trimester (29-34 wks) 0.9 U/kg/dayTerm (35-39 wks) 1.0 U/kg/day
• These are only starting values - blood sugar levels must be optimised rapidly to achieve the target values
• Slightly higher starting doses may be used for obese patients
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Starting doses• The regimens are based on predicted total daily insulin
requirements - based on current weight and stage of pregnancy
• 50% of the total dose is given as a basal dose using NPH insulin (intermediate-acting)
– at bedtime or bedtime+breakfast time
• the other 50% of the total dose - given as boluses before meals using insulin analogues (rapid-acting)
– before meals (within 15 minutes) in divided doses (1/6 of the total dose per meal)
53
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Adjustments• These doses are starting doses only; after
initiating treatment, the insulin doses must be rapidly adjusted to achieve glucose goals
• Insulin dose adjustment is dependant upon home blood glucose monitoring (HBGM) & A1C testing
• Serial sugar testing (SBS) is carried out between 3-7 days after starting insulin & the dosage of insulin adjusted commensurately
54
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HOW DO WE KNOW IF THE DIABETES IS UNDER CONTROL?
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Target Values
• Lowered risks of - birthweight > 4 kg, prematurity, neonatal hypoglycaemia & preeclampsia
• HbA1c levels to < 6% before & during pregnancy predicated outcomes similar to non-diabetic pregnant mothers
56
Rowan et al. Diab Care 2010Prutsky et al. JCEM 2013Wyatt et al. Diab Med 2005
Fasting Glucose
2 hr postprandial HbA1c
≤4.9 mmol/L 5.9–6.4 mmol/L < 6%
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Recommendations -ADA57
ADA. Diabetes Care 2013
Timing Glucose Level
Premeal, bedtime, overnight 3.3–5.4 mmol/L
Postprandial 5.4-7.1 mmol/L
HbA1c 6.0%
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Pillar of assessment
Glycaemic adequacy is assessed through regular blood glucose estimationsMost data regarding target values in pregnancy - derived from pregnant T1DM & T2DM patients
58
Crowther et al. N Eng J Med 2005
Adequate BS control is proven beneficial to the pregnancy. Despite this, no clearly established
• Makes sure no maternal symptoms of DM & hypoglycaemia• Fetal & liquor assessment via P/E & Ultrasound scanning• Biochemical assessment - urine, HBGM & HbA1c
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Assessment of the pregnancy• The pregnancy must be treated as a whole• Take precise history
- maternal well-being, FM• Examine for complications
- remember; maternal, fetal & placental• Investigations - in order of priority– ultrasound scan, urine, blood tests, CTG
59
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Blood glucose Monitoring •Regular blood glucose monitoring - mainstay of objective
optimization of metabolic control–between 3-4 times a day–a prebreakfast and postprandial (2 hours post-lunch
and dinner) and/or night test• Initially, clinic attendance - primarily for patient education
purposes• Subsequently, self-monitoring of blood glucose is the
optimum• Assessment of long-term control and further optimization -
4-6 weekly by measuring HbA1c levels
60
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Postprandial blood glucose monitoring
• Glycaemic control has been shown to be improved by limiting postprandial glucose excursions
• Postprandial glucose correlates well with HbA1C
• By measuring and controlling the postprandial and fasting sugars, the occurrence of neonatal hypoglycaemia and macrosomia may be reduced
61
de Veciana M. NEJM 2013
Do This
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Do not manage the blood sugar, manage the patient!
62
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MANAGING THE DIABETIC PATIENT IN A PRIMARY CARE SETTING
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Diabetic Mx in a primary care setting64
The following are required for adequate management
For internal use only. This training material is for educational purposes. It is not to be used, shared, or discussed with customers. Proprietary & Confidential ©AstraZeneca 2014
Algorithm for pregnancy Mx65
For internal use only. This training material is for educational purposes. It is not to be used, shared, or discussed with customers. Proprietary & Confidential ©AstraZeneca 2014
What to do when a pt screen is positive66
For internal use only. This training material is for educational purposes. It is not to be used, shared, or discussed with customers. Proprietary & Confidential ©AstraZeneca 2014
Evidence of poor glycemic control67
Maternal
Biochemical
Fetalglycosuriapolyuriapolydipsianocturia recurrent infections etc
polyhydramniosmacrosomia
hyperglycaemiaelevated HbA1c
For internal use only. This training material is for educational purposes. It is not to be used, shared, or discussed with customers. Proprietary & Confidential ©AstraZeneca 2014
When to refer68
When to refer to
specialist care
inadequate facilities
inadequate staff
poor patient compliance
poor glycemic control
For internal use only. This training material is for educational purposes. It is not to be used, shared, or discussed with customers. Proprietary & Confidential ©AstraZeneca 2014
You can manage the diabetic if..• You routinely manage antenatal patients• You know how to screen for & diagnose this
condition• You know how to implement & monitor treatment• You know how to monitor for complications
69
Thank you