Dal fetal programming al management clinico
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Dal fetal programming al management clinico
Dichiaro che negli ultimi 2 anni ho avuto i
seguenti rapporti in campo sanitario:
Inviti a meeting da parte di Roche , Menarini,
Medtronic, Lilly, Novo Nordisk
The diabetogenic effect of
Pregnancy
Adapted from McCurdy C. and Friedman JE., 2010
The longitudinal changes in insulin sensitivity
in pregnant women over time
Early pregnancy 12–14 weeks and late pregnancy 34–36 weeks longitudinal changes over time
Catalano P., Reproduction. 2010 ; 140(3): 365–371
The Pedersen/Freinkel Hypothesis
“The concepts of
teratogensis…..
expanded to include
alterations occurring
subsequent to
organogenesis during
the differentiation and
proliferation of fetal
cells. Such
changes could cause
long-range effects upon
behavioral,
anthropometric, and
metabolic functions”
Fuel-mediated
teratogenesis
Freinkel N, Diabetes. 1980;29(12):1023-35
4,697 mothers ages
41.7±5.7 years:
- 4,609 evaluated for
glucose outcomes
HAPO Study
- 25,505 pregnant HAPO FUS
women - 15,812 eligible mother-child
pairs
- 15 centers (nine
-2013–2016
countries) -10/15 HAPO field centers
- 75-g OGTT at 24-32 wks
4,832 children ages 10–14
years:
- 4,160 evaluated for glucose
outcomes
- 4,775 analysed for
overweight/obesity
outcomes.
There is a correlations between maternal
glucose levels and child adiposity
The link between maternal glucose levels
and child adiposity outcomes extends
across the spectrum of maternal glucose
levels, including glucose levels below the
diagnostic threshold for GDM
Lowe WL, 2018
Child glucose outcomes across categories of maternal glucose levels.
Strong positive associations between maternal continuous and
categorical glycemia status with offspring 75-g OGTT IGT, and
IFG, along with inverse associations with IS and oDI.
Maternal FPG was positively associated with offspring FPG, IFG, and A1C and inversely
associated with offspring IS. Moreover, maternal 1-h and 2-h glucose levels were
positively associated with offspring IGT, A1C, and glucose levels during OGTT and
inversely related to offspring IS and oDI.
Denise M. Scholtens et al. Dia Care 2019;42:381-392
©2019 by American Diabetes Association…to a Bigger Metabolic Portrait
Barbour LA., Diabetes Care 2019;42:718–726Glicemie Normali in Gravidanza
Picco della Glicemia dopo pasto (CGMS): 69,4±23.9’
Hernandez T.L et al. Patterns of glycemia in normal pregnancy: should the current therapeutic targets be challenged? Diabetes Care; 34(7):1660-68, 2011
Hernandez Teri L and Barbour Linda A. Review: A Standard Approach to Continuous Glucose Monitor Data in Pregnancy for the Study of Fetal Growth and Infant
Outcomes, Diabetes Technology & Therapeutics Volume 15, Number 2, 1-8, 2013Black: Early pregnancy (12-16 week) Grey: Late pregnancy (28-32 week)
Postprandial Insulin peak
Postprandial Glucose Disposal
….. the optimal timing for prandial insulin is 15 min before meals in early pregnancy and 30–40
min before meals in late pregnancy.
Black: Early pregnancy
Grey: Late pregnancyUltra-Fast-Acting Insulin: Approaching a
More Exact Physiological Insulin Profile
• First-generation rapid-acting
From the normal pancreas
insulins had improved action
Insulin Action (At Mealtime)*
'Faster-acting' insulin profile vs RHI
Rapid-acting insulin • Ultra-fast-acting insulins:
– Better approach physiological insulin
secretion in T1DM
– Replace early insulin secretion in T2DM
RHI
– Have a better profile for pump therapy
Time, h
*Schematic representation.
Home PD. Diabetes Obes Metab. 2015;17:1011-1020.Faster-Acting Insulin Apart Pooled Analysis: Onset and Offset
of Insulin Exposure
300 Faster aspart Ratio (95% CI)
Insulin aspart
Cmax (pmol/L) 1.04 (1.00, 1.08)
250
Insulin aspart serum conc. (pmol/L)
AUCIAsp, 0-12h (pmol·h/L) 1.01 (0.98, 1.04)
200 AUCIAsp, 2-12h (pmol·h/L) 0.89 (0.85, 0.93)*
Treatment Difference (95% CI)
150 –10/–12 min
-9.5 (-10.7, -8.3)*
t50%Cmax (min)
tlate50%Cmax (min) -12.2 (-17.9, -6.5)*
100
50
0
0 1 2 3 4 5 6 7 8
Time (h)
*statistically significant.
(Faster-acting insulin aspart is approved in the US, Canada, EU, Australia [CSII only in the EU].)
Reproduced from Heise T, et al. Clin Pharmacokinet. 2017;56:551-559.Insulin Fasting Asp During
Pregnancy and Laction in
Women With Pre-existing
Diabetes
NCT03770767ABBIAMO SDOGANATO GLI ANALOGHI?
.
Maka S. Hedrington & Stephen N. Davis , 2017
BI: birth injury; DO: delayed ossification; FD:
fetal death; FGR: fetal growth retardation; FN:
fetal nephrotoxicity; LBW: large birth weight;
LI: labor induction; M: macrosomia, NH:
neonatal hypoglycaemia; PD: placental
dysfunction; RD: respiratory distress; SA:
skeletal anomalies;2001-2009 79% R+RF 49%
DEGLUDEC .
NN1250-4300 EXPECT
Study Type : Interventional (Clinical Trial)
Estimated Enrollment : 300 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Masking Description: Sponsor staff involved in the clinical trial is masked
according to company standard procedures.
Primary Purpose: Treatment
Official Title: A Trial Comparing the Effect and Safety of Insulin Degludec
Versus Insulin Detemir, Both in Combination With Insulin
Aspart, in the Treatment of Pregnant Women With Type 1
Diabetes
Actual Study Start Date : November 22, 2017
Estimated Primary Completion Date : October 15, 2021
Estimated Study Completion Date : October 15, 2021NN1250-4300 EXPECT: ITALIA
Site
PI Name Site Number Status
Emanuela Orsi 301 Active
Marina Scavini 302 Active
Elisabetta Torlone 303 Active
Fabio Broglio 304 Active
Annunziata Lapolla 305 Active
Angela Napoli 306 ActiveArm and Intervention/treatment
Arm Intervention/treatment
Experimental: Insulin Degludec Insulin Degludec Drug: Insulin degludec Injection for subcutaneous
once daily and Insulin Aspart 2-4 times daily (s.c., under the skin) use once daily. The total trial
duration for subjects will be maximum 25 months
Drug: Insulin Aspart Injection for subcutaneous (s.c.,
under the skin) use 2-4 times daily with meals. The
total trial duration for subjects will be maximum 25
months
Active Comparator: Insulin Determir Insulin Determir Drug: Insulin Aspart Injection for subcutaneous (s.c.,
once daily or twice daily and Insulin Aspart 2-4 times under the skin) use 2-4 times daily with meals. The
daily total trial duration for subjects will be maximum 25
months
Drug: Insulin detemir Injection for subcutaneous
(s.c., under the skin) use, once daily or twice daily.
The total trial duration for subjects will be maximum
25 monthsTake Home Messages • La gravidanza rappresenta un momento fondamentale per definire lo stato di salute. • Il corredo di farmaci oggi a nostra disposizione ci permette di ottenere target glcemici più stringenti sia nel diabete pregestazionale che nel GDM • Abbiamo sdoganato l’uso degli analoghi e le insuline ultrarapide potranno aiutarci a raggiungere più facilmente i target glicemici post-prandiali • Attendiamo i risultati dello studio EXPECT
I Have a dream…. “Achieve a pregnancy outcome in the diabetic woman that approximates that of the non-diabetic woman.”
GRAZIE PER L’ATTENZIONE
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