Beruflich Dokumente
Kultur Dokumente
51
Triglycerides Insulin
Triglycerides may double by 20 weeks Indicated when target blood glucose levels not
Cholesterol, LDL and HDL may increase 10 -20% attained with diet and physical activity after 2 weeks
Initiate treatment if triglycerides over 1000mg/dl Human insulin should be used less transfer of insulin
52
Insulin Syringe
53
Insulin Practicalities Precautions
Storage Insulin strength may vary (U40, U100)
Ensure the syringe matches the strength!
One month at room temperature once the vial has been openedor
kept in fridge Clear insulins
Long acting insulin analogues
Must never be frozen
Regular/soluble insulin
Store away from source of heat Rapid acting insulin analogues
Cloudy insulin (should not be used if clumps do not
If refrigerator not available, store in clay pot
dissolve on mixing
May be damaged by direct sunlight or vigorous shaking NPH or N
Premixed insulin
Pre-drawn syringes can be kept for one month in fridge (provided
power supply reliable) Identify and differentiate insulin type
Jacobson et al . 2005
54
However
Glucose lowering medications
Latest evidence suggests:
glibenclamide is associated with worse
outcomes compared to insulin and metformin
Need more studies in this area
Metformin
Hence glibenclamide is not recommended in the
Does cross the placenta
routine management of GDM
Does not appear to have adverse effects on the fetus
May be used in polycystic ovarian syndrome to improve
Feig, Moses, 2011
Balsells et al, 2015
fertility and decrease spontaneous abortion rate
55
Other oral agents Final word on oral agents
There is insufficient data on the use of other If a woman is on oral agents when diagnosed with
antidiabetic agents such as
GDM
meglitinides,
alpha glucosidase inhibitors, -Discontinue them
thiazolidinediones, -Start diet and exercise plan
GLP-1 agonists and DPP-4 inhibitors
-Monitor blood glucose
The use of these agents in pregnancy cannot
be recommended -Start insulin
References
Canadian Diabetes Association Clinical Practice Guidelines Expert Committee. Canadian Diabetes Association 2013
Clinical practice guidelines for the prevention and management of diabetes in Canada; Diabetes and pregnancy. Can J
of Diabetes. 2013;37(suppl 1):S168-183.
Feig DS, Moses RG. Metformin during pregnancy. Diabetes Care. 2011;34:2329
Goldenberg I, Benderly M, Goldbourt U. Update on the use of fibrates: focus on bezafibrate. Vasc Health Risk Manag.
2008 February;4(1):131141.
Jacobson et al - Comparison of glyburide and insulin for the management of gestational diabetes in a large managed
care organization, American Journal of Obstetrics and Gynecology 2005
Kitzmiller JL, Block JM, Catalano PM, et al. Managing preexisting diabetes for pregnancy: Summary of evidence and
consensus recommendations for care. Diabetes Care. 2008;31(5):1060-1079.
Rowan JA, Hague WM, Gao W. et al. Metformin versus Insulin for the Treatment of Gestational Diabetes. NEJM
2008;358:2003-15
56
Objectives
Definition of hypoglycemia
Risk of hypoglycemia (1 of 3)
1. The development of autonomic or
Only those taking glucose -lowering medicines
neuroglycopenic symptoms
or insulin are at risk
2. Low plasma glucose (less than 4.0 mmol/L or
Risk increases with:
72 mg/dl)
Not enough carbohydrate consumption
3. Symptoms resolved by administration of Late or missed meal
carbohydrate Fasting or malnourishment
Too much insulin
Prolonged or unplanned activity
Cryer, Davis, Shamoon, 2003
57
Canadian Diabetes Association, 2013
Coustan, 2009
Diamond, Reece et al, 1992
Nisell, Persson , et al1994
Reece, Hagav, et al 1995
58
Treatment
Severe
20 g glucose
Glucagon 1ml SC or IM; increases BG by 3 -12 mmol/L
(54-216 mg/dl) over 60 min
IV dextrose- 20 to 50 ml of 50% dextrose over 2 to 3
minutes; immediate response is seen
Manage seizure- place person on their side if not too
Meal or snack (15 to 20 g carbohydrate + a protein Preterm labour in GDM can use steroids and
tocolysis as for other pregnancies
source)
Next dose of insulin taken as usual if cause is known Preferably avoid betamimetic as tocolytics
and hypo was mild Nifidepine is a good choice
Consider reducing next dose of insulin if hypo was Both steroids / tocolytics can push glucose up so
severe need to monitor closely and cover with insulin /
Assess cause and prevent recurrence increasing dose of insulin
Avoid BG levels < 4 mmol/L (72 mg/dL) Rule out UTI as a risk factor for preterm labour
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Preeclampsia
Hollander 2007
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Timing of delivery
Consider.
TOO
LATE? Gestational specific risks for still birth continue to
EARLY
fall up to 38 weeks but increase slightly over 40
weeks
RDS LATE
IUFD In insulin dependent women most would plan
delivery 38 - 39 weeks
PREMATURITY MACROSOMIA
Between 38 and 39 weeks
No difference in incidence of cesareans
More larger babies in one study
There is as yet not enough evidence that induction in
diabetic pregnancies prevents fetal macrosomia
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Monitoring labour
References
COMPLICATIONS
Labour is a time of unpredictable glucose and insulin Canadian Diabetes Association Expert Committee. Canadian Diabetes Association 2013 Clinical Practice Guidelines
demands risk of hypoglycemia for the Prevention and Management of Diabetes in Canada. Can J Diab 2013;37(suppl 1):S69-71
Coustan , D, Glob. libr. women's med., (ISSN: 1756-2228) 2009; DOI 10.3843/GLOWM.10162
Sliding scale / infusion Cryer P.E. Davis, S.N. Shamoon , H. Hypoglycemia in diabetes. Diabetes Care, 2003;26(6):1902-1912
Diamond MP, Reece EA, Caprio S et al: Impairment of counterregulatory hormone responses to hypoglycemia in
Maintain plasma glucose below 110 mg/dl to avoid maternal pregnant women with insulin -dependent diabetes mellitus. Am JObstet Gynecol 1992;166:70-77
hyperglycemia and subsequent foetal hypoglycemia Hollander M, Paarlberg KM, Huisjes AJM, 2007 Gestational Diabetes: A Review of the Current Literature and
Guidelines Volume 62, Number 2 Obstetrical and Gynecological Survey
Careful intrapartum FHR monitoring Nisell H, Persson B, Hanson U, et al: Hormonal, metabolic and circulatory responses to insulin -induced hypoglycemia
in pregnant and nonpregnant women with insulin -dependent diabetes. Am JPerinatol 1994;11:231-236
Reece EA, Hagay Z, Roberts AB et al: Fetal Doppler and behavioral responses during hypoglycemia induced with the
Pay attention to second stage slow progress is a insulin clamp technique in pregnant diabetic women. Am J Obstet Gynecol 1995;172:151-155.
red flag Saleh M., Grunberger, G. Hypoglycemia: A cause for poor glycemic control. Clinical Diabetes, 2001;19(4):161-167.
DELIVERY
Caution with instrumental delivery Jovanovic L, Knopp RH, Kim H, et al. Elevated pregnancy losses at high and low extremes of maternal glucose in early
normal and diabetic pregnancy: evidence for a protective adaptation in diabetes. Diabetes Care 2005; 28:1113.
Be prepared for shoulder dystocia Patel RR, Steer P, Doyle P, Little MP, Elliot P. Does gestation vary by ethnic group? A London-based study of over
122000 pregnancies with spontaneous onset of labour. Int J of Epid. 2003;33:107-113.DOI: 10.1093/ijc/dyg238.
Jovanovic L. 2005
62
Objectives
Pre-warmed incubator
After each of 1st 4 feeds
Start breast feeding within 30 minutes for better latching
Less than 2.6 mmol/L or 44 mg/dl defined as
Watch for jaundice check bilirubin
hypoglycemia
If macrosomic, check calcium and magnesium on day 2
Treatment of hypoglycemia
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Breast feeding
Gunderson, 2007
Future pregnancies
Post partum period
Should be planned
Encourage mother to achieve healthy weight. Education regarding birth control is needed
Healthy eating Encourage achieving healthy weight prior to
Adequate intake to sustain breast feeding conceiving again
Regular activity
Check blood glucose levels well ahead of
conception allowing time to normalize if necessary
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Glucose tolerance testing
Any method of contraception can be safely used in Fasting glucose testing is not sufficient to
a woman with history of GDM identify all who have IGT or type 2 diabetes
Intrauterine devices are commonly used
Only 34% of women with IGT or type 2 had elevated
fasting glucose levels
44% of those with type 2 had fasting less than 5.5
Progesterone-only oral contraceptives are the best mmol/L (100 mg/dL)
choice within the first 6 weeks post partum
OGTT should be done
They have the lowest risk of thrombosis
Preferred during breastfeeding
Metzger, Buchanan, Coustan et al. 2007 Metzger, Buchanan, Coustan et al. 2007
65
References
Gunderson EP. Breastfeeding after gestational diabetes pregnancy. Diabetes Care. 2007;30(suppl 2):S161-168.
Metzger BE, Buchanan TA, Coustan DR, De Leiva A, Hadden DR, Hod M. Summary and recommendations of
the fifth international workshop-conference on gestational diabetes mellitus, Diabetes Care. 2007; 30(suppl
2):S251-260.
Seshiah V, Balaji V, et al. Gestational Diabetes Mellitus Guidelines. J Assoc Physic of India 2006;54:622-28.
66
Case study #1: Mrs. C
Mrs. C.
Mrs. C
Her results are as follows. Her results on the 75 gm glucose load (fasting) are as
follows.
Time 0 hr (Fasting)
Time 0 hr (Fasting) 1 hour 2 hour
Glucose 4.7 (86) Glucose 4.8 (88) 10.3 (186) 8.9 (161)
mmol/L(mg/dL) mmol/L(mg/dL)
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Mrs. C
Mrs. C
Mrs. C Mrs. C
Mrs. C is now on 6 units of NPH insulin at bedtime in Her insulin dose has stabilized
addition to 4 units of rapid acting insulin before breakfast.
NPH 8 units at bedtime
She starts complaining of excess hunger during the early
rapid acting insulin 6 u before breakfast, 4 units before lunch
and 4 units before evening meal.
hours of the morning.
Mrs. C goes into labour at 39 weeks.
Her reports are as follows. Should she have been induced earlier?
mmol/L (mg/dL)
Fasting BG 3.3 (61)
Should a C-Section be considered?
2 hour postprandial BG 5.6 (102)
Are these values acceptable? How should her insulin be managed during labour
and delivery?
What is the next line of treatment?
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Case study #2: Mrs. S
Mrs. C
Mrs. S is a 35 year old nulliparous lady and has suffered
Following delivery, blood glucose levels normalised and two miscarriages in the last three years.
she was able to stop insulin.
After the last miscarriage she was diagnosed with PCOS
After 6 weeks, she underwent an OGTT, the results of and has been on metformin since.
which are as follows.
She did not test her blood glucose levels during either of
Time 0 hour (Fasting) 2 hours
her previous pregnancies.
Glucose mmol/L 4.5 (82) 7.0 (127)
(mg/dl)
Her mother has diabetes.
What is the diagnosis?
What is her risk of developing diabetes in the future? She presents at 12 weeks gestation
When should she be tested next?
What else do you need to know?
Mrs. S
Mrs. S
Mrs S has an OGTT at 13 weeks gestation
Does she need to be screened for diabetes?
If so, when? Fasting 2 hour
Glucose 6.0 (108) 9.0 (162)
mmol/L(mg/dl)
What screening test is to be used?
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Mrs M
Case Study #3: Mrs M Fasting BG at 6 weeks
Fasting
Mrs. M, 30/F Primigravida 8.8 mmol/L (160 mg/dL)
LMP: 13/10/12 EDC : 28/07/13 Regular cycles What would you advise now?
Spontaneous conception 10 months after marriage Trial of MNT or medications right away?
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Mrs M Mrs M
Mrs M
Uterine contractions settle. UTI picked up and treated with
appropriate antibiotics
Mrs M
She is now 37 weeks
Tocolytic which drug and dose FBS 5.5mmol/L (100mg/dL) 1 hr PPBS 8.3 mmol/L (150
mg.dL) on
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Case Study #4
Mrs. C, a 32 year old primigravida
Reports for the first antenatal checkup.
She is obese with a body mass index of 35kg/m 2, both her parents
have diabetes.
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WORLD DIABETES FOUNDATION
Original Article jk"Vh; LokLF; fe'ku
Can the management of blood sugar levels in gestational diabetes mellitus cases be an
indicator of maternal and fetal outcomes? The results of a prospective cohort study
from India.
Rajesh Jain, Sanjeev Davey1, Anuradha Davey2, Santosh K. Raghav1, Jai V. Singh1
Gestational Diabetes, Prevention Control Project, Jain Hospital, Kanpur,1 Department of Community Medicine,
Muzaffarnagar Medical College and Hospital, Muzaffarnagar,2 Department of Community Medicine, Subharti Medical
College, Meerut, Uttar Pradesh, India.
BACKGROUND: Gestational diabetes mellitus (GDM) is emerging as an important public health problem in India owing to its
increasing prevalence since the last decade. The issue addressed in the study was whether the management of blood sugar levels in GDM cases
can predict maternal and fetal outcomes.
MATERIALS AND METHODS: A prospective cohort study was done for 2 year from October1, 2012, to September 31, 2014, at 198
diabetic screening units as a part of the Gestational Diabetes Prevention and Control Project approved by the Indian Government in the
district of Kanpur, state of Uttar Pradesh. A total of 57,108 pregnant women were screened during their 24-28th weeks ofpregnancy by
impaired oral glucose test. All types of maternal and perinatal outcomes were followed up in both GDM and non-GDM categories in the 2nd
year (2013-2014) after blood sugar levels were controlled. RESULTS: It was seen that for all kinds of maternal and fetal outcomes, the
differences between GDM cases and non-GDM cases were highly significant (P < 0.0001, relative risk > 1 in every case). Moreover, perinatal
mortality also increased significantly from 5.7% to 8.9% when blood sugar levels increased from 199mg/dl and above. Perinatal and maternal
outcomes in GDM cases were also significantly related to the control of blood sugar levels (P < 0.0001).
CONCLUSION: Blood sugar levels can be an indicator of maternal and perinatal morbidity and mortality in GDM cases, provided
unified diagnostic criteria are used by India laboratories. However, to get an accurate picture on this issue, all factors need further study.
It was seen that for all kinds of maternal outcomes suchas cesarean section, pregnancy-induced bypertension (PIH), premature baby unit (PBU) care,
family H/O DM and antepartum hemorrhage / postpartum hemorrhage (APH / PPH), the differences between GDM and non-GDM cases were highly
statistically significant (P < 0.0001, RR > 1 in every case). This was also seen in the outcomes of neonates in terms of perinatal death, stillbirth, neonatal
death, congenital malformations, low gestation for age (LGA), low birth weight (LBW), jaundice. Here also the differences between GDM and non-GDM
case were statistically significant (P < 0.0001, RR > 1 in every case) [Table 1].
In terms of H/O previous birth complication, again in the category of stillbirths and perinatal deaths both in GDM and non-GDM cases, the differences
were statistically significant (P < 0.0001). However, in neonatal deaths, it was not significant in both GDM and non-GDM category (P > 0.05) [Table 2]
As the blood sugar level rose above 120 mg/dl, perinatal mortality rose significantly as compared to previous perinatal loss (P < 0.0001). This increased
significantly from (5.7% to 8.9%) when blood sugar level was >199 mg/dl [Table 3 and Figure 1].
Table 1 : Maternal and fetal outoomes of gestational diabetes mellitus and nongestational diabetes mellitus
pregnant women
Outcomes GDM cases (n=7641) Non-GDM cases (n=8000) RR 95% CI p-value
N (%) N (%)
Stillbirth 247 (3.2) 102 (1.3) 2.53 2.0-3.1 <0.44
Neonatal death 128 (1.7) 56 (0.7) 2.39 1.75-3.27 <0.0001
Perinatal death 375 (4.9) 158 (1.97) 2.48 2.0-2.9 <0.0001
Congenital malformation 382 (5) 82 (1.03) 4.87 3.8-6.1 <0.0001
Cesarean section 2242 (29.3) 1814 (22.67) 1.21 1.2-1.3 <0.0001
PBU Care 234 (3.06) 85 (1.06) 2.88 2.25-3.68 <0.0001
LGA 684 (9) 67 (.83) 10.6 8.3-13.7 <0.0001
LBW 863 (11.3) 758 (9.4) 1.19 1.1-1.3 <0.0002
PIH 686 (9) 483 (6) 1.83 1.6-2.0 <0.0001
Jaundice 382 (5) 84 (1) 4.76 3.7-6.0 <0.0001
Family history of DM 1372 (17.9) 546 (6.8) 2.62 2.3-2.8 <0.0001
APH/PPH 64 (.0.84) 26 (0.32) 2.57 1.6-4.0 <0.0001
APH : Antepartum hemorrhage, PPH : Postpartum hemorrhage; PIH : Pregnancy-Induced hypertension; LBW: Low birth weight; LGA: Low gestaion for
age; PBU: Premature baby unit; OR : Odds ratio, RR : Relative risk; DM : Diabetes mellitus; GDM : Ges : Gestational diabetes mellitus
Table 2 : Fetal outoomes in gestational diabetes mellitus versus nongestational diabetes mellitus and its relationship with
history of previous birth complications
Outcomes in GDM cases Previous fetal loss p- value GDM absent Previous fetal loss p- value
neonate (n=7641) present (n=8000) present
N (%) N (%) N (%) N (%)
Stillbirth 247 (3.2) 916 (12) <0.0001 102 (1.2) 212 (2.6) <0.0001
Neonatal death 128 (1.7) 156 (2) <0.09 56 (0.7) 62 (9.8) <0.5
Perinatal death 375 (4.9) 1072 (14) <0.0001 158 (1.9) 274 (3.4) <0.0001
GDM : Gestational diabetes mellitus
Table 3 : Perinatal mortality as a function of blood sugar (mg/dl) vbalue and its comparison with a
history of previous perinatal loss
Blood gugar Samples tested Perinatal mortality History of previous p-value
levels (mg/dl) (n=57,018 present N (%) perinatal mortality N (%)
<100 n1=12,560 - -
100-119 n2=31,075 776 (2.4) 768 (2.5) <0.0001
120-139 n3= 5742 137 (2.4) 214 (3.7) <0.0001
140-159 n4=3915 137 (3.5) 417 (10) <0.0001
160-179 n5=1451 65 (4.4) 176 (12.1) <0.0001
180-199 n6 = 940 54 (5.7) 168 (17.8) <0.0001
200 n7=1335 119 (8.9) 311 (23.2) <0.0001
The most important finding in our study was that as blood sugar levels rose above 120 mg/dl, there was significant
perinatal mortality compared to previous perinatal loss (P <0.0001). This perinatal loss increased significantly from
(5.7% to 8.9%), when blood sugar levels was 199 mg/dl. This finding was also unique in contrast to many related
[19-26]
studies. It has been seen that the values of oral glucose tolerance test in the middle phase of pregnancy and
antenatal random glycemia can to some extent also predict PIH, preterm births, or stillbirths. [20]
DISCUSSION
DM is increasing worldwide and this rise is more prevalent in developing countries such as India, which is going to become the future "Diabetic-Capital,"
for which GDM is thought be a real contributor[12]. This emphasizes the importance of prevalence studies in India in pregnant women in order to reveal
the exact prevalence of GDM. [12] Hence, GDM is emerging as a rising public health problem in pregnant women in India as many studies have
indicated. [5,12-15]
40
10
35 35.9 BS Controlled (in %)
9 8.9
% of GDM Cases with Blood Sugar levels
BS Uncontrolled (in %)
8 30
Relative Risk
7 25
22.6
6 5.7 20
5 15 15.6
4 4.4
3.5 10 9.3
3 7.5
2 24 24 5
3.3
5.1 5.2
2.7
1.8 0.8 1.1
0
1 irth ath are GA IH ice se
de ath S
LB
W P DM PP
H
0 ll b ld
e ean c L
un
d
H/ nU
Sti al
ata sar PB
U
Ja H/O uli
aty Ce ly AP Ins
on rin mi
100-119 120-139 140-159 160-179 180-199
200 Ne Pe F a
Maternal & Neonatal Outoomes
Figure 1 : Perinatal mortality (%) in gestational diabetes mellitus cases in relation to the Figure 2 : Maternal and perinatal outcomes (in %) in gestations diabetes mellitus cases in relation to the
maternal blood sugar levels controlled by treatment (in g/dl).
maternal blood sugar levels (in g/dl)
APH : Antepartum hemorrhage, PPH : Postpartum hemorrhage; PIH : Pregnancy-Induced hypertension; LBW: Low birth weight; LGA: Low gestation for age;
PBU: Prematurebaby unit; BS : Blood Sugar; OR: Odds ratio; RR: Relative risk; DM: Diabetes mellitus
CONCLUSION
Maternal and fetal outcomes in GDM cases are poor. Perinatal and maternal outcomes in GDM cases are also signficantly
related to control or blood sugar levels. Therefore, blood sugar levels appear to be an important possible indicator of
maternal and perinatal morbidity and mortality in Indian GDM cases. However, there is a need to unify diagnostic
criteria in practices throughout the Indian subcontinent for a better validation of results from this study as well as other
GDM studies conducted in India.