Transcript VIRAL FEVER WITH ARTHRITIS – AN OVERVIEW

GESTATIONAL DIABETES MELLITUS CURRENT CONCEPTS
Dr.Vivek Sundaram.MD.DNB.MRCP(UK)
Consultant – Internal Medicine,Diabetes & Critical Care
Sundaram Hospital,Trichy.
Watching TV for 2 hours/day increases
Risk of diabetes by 20%....JAMA,June 2011
ARETAEUS(200 A.D.)
“….wonderful affliction with melting down of flesh
and limbs into urine…..patient never stops making
water ..……illness is chronic but the patient
shortlived”
Definition

Gestational Diabetes Mellitus (GDM) is defined as “carbohydrate intolerance with recognition or onset during
pregnancy, irrespective of the treatment with diet or
insulin.”
The importance of GDM is that two generations are at
risk of developing diabetes in the future.


The maternal metabolic adaptation is to maintain the mean FBG
of 74.5 ± 11 mg/dl and the PPG peak of 108.7 ± 16.9mg/dl.1
Compensatory hyperinsulinaemia due to insulin resistance.
Failure of beta cells secretion to overcome the insulin resistance
leads to GDM.
Diabetes and Pregnancy – Why it is relevant?
Hyperglycaemia
during pregnancy is
associated with high
risk of maternal and
perinatal morbidity
and mortality
Diagnosis of GDM
identifies women at
high risk of future
diabetes, offers
opportunity of
primary prevention
Maternal
hyperglycaemia is
associated with
development of
type 2 diabetes in
the offspring
GDM………

Pregnancy – diabetogenic condition (metabolic stress test)
Unmasks
A
a compensated metabolic abnormality
direct consequence of the altered maternal metabolism
stemming from the changing hormonal milieu.
GDM prevalence linked to background IGT rates
GDM
2%
1980s
1990s
Agarwal S, Gupta AN. Gestational
Diabetes. J Assoc Physicians India
1982;30:203
7.6%
Narendra J, Munichoodappa C, et al, Prevalence
of glucose intolerance during pregnancy. Int J
Diab Dev Countries 1991;11:2-4
16.6%
2000s
V Seshiah, V Balaji, Madhuri S Balaji, CB
Sanjeevi, A. Green. Gestational Diabetes Mellitus
in India. J Assoc Physicians India 2004;52:707
IGT
2%
Ramachandran A, et .al., High prevalence
of diabetes in an urban population in south
India. BMJ 1988;3; 297(6648):587-90
8.2%
Ramachandran A, Snehalatha c, Dharmaraj D,
Viswanathan M. Prevalence of glucose
intolerance in Asian Indians. Diabetes Care
1992; 15:1348-55
14.5%
Ramachandran A, Snehalatha C, Kapur A, Vijay V,
Mohan V,Das AK, Rao PV, Yajnik CS, Prasanna
Kumar KM, Nair JD.For the Diabetes
Epidemiology Study Group in India
(DESI).Diabetologia 2001;44:1094-1101.
FREINKEL HYPOTHESIS
Uterine
At Birth
Macrosomia
After Birth
Obesity
Hypoglycemia
placenta
Maternal DM
A.A
Fat
CHO
Metabolic syndrome
Amniotic Fluid Insulin
IGT/DM
Fetus
CVD
Pathophysiology
• Human Placental Lactogen (HPL)
– Produced by syncytiotrophoblasts of placenta.
– Acts to promote lipolysis  increased Free fatty acids
contributing to tissue insulin resistance.
• Estrogen and Progesterone
– Interfere with insulin-glucose relationship.
• Insulinase
– Placental product that may play a minor role.
Pathophysiology
Normal pregnancy :
- Mild fasting hypoglycemia –
increased lipolysis and FFAs
become the main fuel substrate
for the mother ( Mediated by
human placental growth
harmone)-”accelerated
starvation”
- Postprandial hyperglycemia –
insulin resistance aids glucose
transfer to the fetus –”facilitated
anabolism”
GDM –POSTPRANDIAL HYPERGLYCEMIA IS MORE
RELEVANT
Fetal renal thershold for glucose < 110 mg/dl
Maternal hyperglycemia (>110 mg/dl) – increased iv
glucose load to the fetus producing fetal glycosuria
Fetal polyuria - polyhyramnios
20 wks GA – fetus ingests glucose rich amniotic
fluid
Gut stimulus to insulin secretion is more potent
than transient iv hyperglycemia
IV + Oral route (glucose) – overfed,fat fetus
Risk Factors

Age  35 years

Obesity (BMI  30 kg/m2)

Family history

INDIAN
Previous delivery-ofETHNICITY
a macrosomic infant

Member of a high-risk population

Polycystic ovarian syndrome

Previous abnormal glucose tolerance
GDM dilemmas

Early or late sreening?

To treat or not ?

WHO or ADA criteria

Insulin or pills?

One step or twostep?

Early or late delivery?

75 or 100 gm?

C section or normal?

1 hour or 2 hour?

Breast feed or not?
Who & When to screen?
UNIVERSAL

First booking – Differentiates pre GDM from GDM

24-28 weeks [ Repeat - GTT]

32 -34 weeks [ Repeat -GTT]
How to screen?
One Step Approach – Validated in the indian population

2 hrs value >140 mg/dl with 75g oral glucose -GDM
( irrespective of the time last meal was consumed)
Definitive test: 75gm 2 hour OGTT ( ADA Criteria)

If negative rescreen at 24 weeks /32 weeks

If positive proceed to treatment
Gestational DM-Revised ADA criteria
(2011)
75 g OGTT at 24-28 wks of gestation
Fasting
>_ 92 mg/dl
1 hr
>180
mg/dl
_
2 hr
_>
153 mg/dl
ANY 1 ABNORMAL VALUE - GDM
100 g OGTT – O,I,2,3 hr values …. 95,180,155,140 …2 abnormal values
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“Abnormal” Plasma Glucose during Pregnancy
The occurrence of macrosomia was continuum
as the 2 hr plasma glucose increased from 120
mg/dl (adjusted odds ratio 3.02 [ 95% CI 1.30 –
7.00], P < 0.05])
Balaji V, Balaji MS, Seshiah V, Mukundan S, Datta M.Diabetes Res Clin Pract. 2006
Aug;73(2):223-4.
Occurrence of birth weight of new born > 90th
percentile was continuum as FPG increased
from 80 mg/dl and was significant above 90
mg/dl (adjusted odds ratio 2.08 [ 95% CI 1.24 – 3.48],
P = 0.005])
V Seshiah, V Balaji, Madhuri S Balaji, A Paneerselvam. Abnormal Fasting Plasma Glucose during
Pregnancy. Diabetes Care vol 31 (12): e92, December 2008
Abnormal : FPG > 90 & PPG > 120 mg/dl
19
TARGET BLOOD GLUCOSE LEVELS
Fasting PG
PPG
Mean PG level
80 mg %
110 mg %
95 mg %
90 mg %
120 mg %
105 mg %
Balaji V, Balaji MS, Seshiah V, Mukundan S, Datta M.Diabetes Res Clin Pract. 2006 Aug;73(2):223-4.
V. Seshiah, AK Das, Balaji V, Shashank Joshi, MN Parikh, Sunil Gupta for DIPSI. GDMGuidelines. JAPI vol 54, 2006, 622-28
Oded Langer. Maternal glycemic criteria for insulin therapy in GDM. Diabetes
care, vol 21 (2), August 1998. B91-98.
Birth weight between
2.5 and 3.5 Kg
Vinod K Paul, Ashok K Deorari, Meharban Singh. Management of Low Birth Weight Babies.
In: IAP Textbook of Pediatrics. 2nd ed. A. Parthasarathy, editor. Jaypee publications, 2002,
p60.
GDM – Fetal Morbidity
• Macrosomia of the baby
• CPD – Shoulder Dystocia
• Intrapartum Trauma – Feto-maternal
• Neonatal Hypoglycemia
• Neonatal Hypocalcemia
• Neonatal Hyperbilirubinemia
• Respiratory Distress Syndrome (RDS)
• Polycythemia (secondary) in the new born
20
Fetal Morbidity
Maternal Morbidity
• Hypertension/Preeclampsia and Eclampsia
• Cesarean delivery; Pre term labour
• Polyhydramnios – fluid > 2000 ml
• Post-partum uterine atony
• Abruptio placenta
• 40-60% risk of DM (screen 6 wk/6 mths after delivery)
22
MANAGEMENT
Aim
To maintain plasma glucose
values as to that of non diabetic
pregnancy
How to treat?

Medical nutrition therapy (MNT)

Exercise

Insulin
MNT

2 wk trial – if uncontrolled switch over to insulin

30 kcal/kg/day for 60 kg

BMI>30- 25kcal/kg/day

300 extra calories for 2 & 3 trimester

3 meals & 3 snacks - avoid hypoglycemia

40 – 50% of calories as CHO,25% each as fat and protein
Exercise
• Women with GDM often need
regular, moderate physical activity
to help control their blood sugar
levels by allowing insulin to work
better.
• Examples include:
– Walking
– Prenatal aerobics classes
– Swimming
Keep in mind that it
may take 2 to 4 weeks
before physical
activity has an effect
on blood sugar levels.
Insulin therapy

Safe ,Effective, time tested

Human Insulin preferred

Short acting analogues – good option

May need short term hospitalization

Monitoring fasting, premeals & post meal
CHARLES BEST –FRED BANTING
Insulin secretion defect in diabetes
Normal
Diabetes
Plasma-immunoreactive
Insulin (µU/mL)
Plasma-immunoreactive
Insulin (µU/mL)
1ste fase
(acute afgifte)
120
120
100
100
80
80
60
60
40
40
2e fase
20
20
0
0
-30
0
30
60
Time (min)
90
120
Fonseca V. Curr Med Res Opin 2003;19:635–641.
-30
0
30
60
90
Time (min)
120
Insulin therapy should closely mimic normal insulin physiology
Basal needs: Intermediate-/long-acting insulins (NPH, ILPS, detemir, glargine)
Bolus needs: Rapid-/short-acting insulins given with meals
(lispro, aspart, glulisine, human regular insulin)
Meal
Meal
Meal
Expected insulin changes during the day for individuals without diabetes
Insulin effect images are theoretical representations and are not derived from clinical trial data.
• Normal insulin physiology is matched by multiple insulin
injections
30
Insulin
Onset
Peak
Duration
Short acting
Regular
30-60 min
2-4 h
Lispro/aspart
5-15 min
1-2 h
4-6 h
3-4 h
Glulisine
Intermediate acting
NPH
1-4 h
4-8 h
10-20 h
Glargine
1-2 h
Flat
~24 h
Detemir
1-4
Flat
Long acting
12-20
So, Why Modern Insulins ?
Dissociation of Insulins
Regular Human Insulin
10-3 M

10-3 M
10-5 M

10-8 M
Peak time
2-4 hr

Formulation
Capillary membrane
Analogs
10-3 M

10-3 M
10-3 M

Formulation Transient
Peak time
1 hr
 Inability of s.c. injected soluble insulin to mimic the
physiological pattern
 Delayed onset of action (30-60 min after injection)
i.e. should be injected 30-60 min prior to a meal
 Prolonged duration of action (6-8 hrs after injection)
 Inadequate insulin when in need
 Insulin when not needed
Slide no 34
Presentation title
Presentation title
•
Date
Slide no
35
Physiological insulin profile:
basal component
meal-related peaks
•
Regular insulin fails to match
normal insulin peak
Fails to match the physiology
Presentation title
•
Date
Slide no
36
Physiological insulin
profile: basal component
meal-related peaks
Period of unwanted
hyperglycemia
Period of unwanted
hypoglycemia
•
Mixtard fails to re-create the
physiological insulin profile
Premixed is a suspension of:
Soluble insulin analogue
30%
30%
Protamine-crystallised
insulin
Soluble
human insulin
NPH
Slide no 37
Presentation title
Date
INSULIN TACTICS
Twice-daily Split-mixed Regimens
Insulin Effect
Regular
NPH
B
L
S
HS
B
6-
INSULIN TACTICS
Multiple Daily Injections (MDI):NPH + Mealtime Lispro
NPH at AM and HS + Lispro AC
NPH at HS + Lispro AC
Insulin Effect
Lispro
NPH
Insulin Effect
Lispro
NPH
B
L
S
HS
B
B
L
S
HS
B
6-
Insulin Regimen
• If MNT fails after 2 wks of trial initiate Insulin
• Dose: 0.7, 0.8 and 0.9 u/kg – 1, 2 & 3 trim.
Eg. 1st trim – 64 kg = 0.7 x 64 = 45 units
• Give 2/3 before BF = 30 units of 30:70 mix
• Give 1/3 before supper = 15 u of 30:70 mix
• Increase total dose by 2-4 units based on BG
40
Oral agents -GDM
Glibenclamide ( Currently not recommended)
Metformin – Select group ( pre GDM/PCOS)
ADVANTAGES
Easy to take
Need far less education
Affordable
No social stigma
Not endorsed by any formal recommendations apart from NICE Guidelines
Original Article
Metformin versus Insulin for the Treatment of
Gestational Diabetes
Janet A. Rowan, M.B., Ch.B., William M. Hague, M.D., Wanzhen Gao, Ph.D., Malcolm
R. Battin, M.B., Ch.B., M. Peter Moore, M.B., Ch.B., for the MiG Trial
Investigators
N E J M.358(19):2003-2015
May 8, 2008
Monitoring HbA1c Levels

HbA1c in early pregnancy - differentiates between a pre
gestational diabetic and GDM. If the HbA1c level is more
than 6%, she is likely to be a pre GDM.

HbA1c is useful in monitoring the glucose control during
pregnancy, but not for the day to day management.
Estimation of fructosamine during pregnancy is less
frequently used.
Conclusions

Universal screening ideal for our women

2 hour 75 gm screening is cost effective

2 hour 75 gm – GTT ( Definitive test)

Diet and exercise provides good control in many

Insulin analogues are safe and very effective

Oral agents are an alternative – in select situations

Postpartum follow-up is an integral part of GDM
management
Remember how fortunate we are to be
included in the lives of our patients at the
most precious times of their lives
RICHARD S. HOLLIS
PRESIDENT ACOG
ILLNESS
WELLNESS
THANK YOU