Vitamin d adipocytokines
This presentation is the property of its rightful owner.
Sponsored Links
1 / 67

Vitamin D Adipocytokines PowerPoint PPT Presentation


  • 43 Views
  • Uploaded on
  • Presentation posted in: General

Vitamin D Adipocytokines. ….and GDM pregnancies. Objectives: . To review the role for Vit D as an insulin-sensitizing hormone, with particular reference to GDM pregnancy To review some of the roles for adipocytokines in insulin resistance and GDM pregnancy

Download Presentation

Vitamin D Adipocytokines

An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -

Presentation Transcript


Vitamin d adipocytokines

Vitamin DAdipocytokines

….and GDM pregnancies


Objectives

Objectives:

  • To review the role for Vit D as an insulin-sensitizing hormone, with particular reference to GDM pregnancy

  • To review some of the roles for adipocytokines in insulin resistance and GDM pregnancy

  • To review our local experience with VitD/adipocytokines in GDM women and their neonates


But first back to med school for a moment

But first….back to med school for a moment


Vitamin d a few reminders

Vitamin D: a few reminders

  • Ergocalciferol(D2): provitamin form

  • Cholecalciferol(D3): inactivated, unhydroxylated form

  • 25(OH) Vit D3: this from is the least variable, and considered best measure of sufficiency. Therefore, most common form measured.

  • 1, 25(OH) Vit D3: this form is variable. Measured in odd rare conditions such as Vit D resistant rickets


Vitamin d a few reminders1

Vitamin D: a few reminders

  • Ergocalciferol(D2): provitamin form

  • Cholecalciferol(D3): inactivated, unhydroxylated form

  • 25(OH) Vit D3: this form is the least variable, and considered best measure of sufficiency. Therefore, most common form measured. This is the form that will appear in this talk as VitD

  • 1, 25(OH) Vit D3: this form is variable. Measured in odd rare conditions such as Vit D resistant rickets


Vitamin d recent oddities

Vitamin D: recent oddities

  • We usually think of Vit D as promoting bone health

  • The last few decades have illustrated that Vit D has hormone properties

  • structural similarities with testosterone, steroids, cholesterol


Cholecalciferol

….cholecalciferol


Cholesterol

…….cholesterol


Vit d and gdm what do we know

Vit D and GDM: what do we know?

  • Vit D deficiency suspected to be a risk factor for glucose intolerance

  • For instance:

  • 54 GDM, 39 IGT; 11 controls, matched for age, BMI, pregnancy week 24-28

  • [NB: Iranian study]

    SoheilykhahNutrClinPract 2012. 25. 524


Vitamin d adipocytokines

CONCLUSIONS:

  • 83% GDM and IGT women had VitD <20ng/ml

  • vs

  • 71.2% Controls (p=0.03)

  • Lowest VitD levels were in GDM women compared to Controls


Does vit d status predict gdm risk

Does Vit D status predict GDM risk?

  • 953 pregnant women in USA

  • Nested case/control study

  • VitD level taken at 16 weeks gestation

  • 57 women developed GDM

  • Zhang Plos One 2008.3.e3753


Vitamin d adipocytokines

CONCLUSIONS

  • VitD at 16 wks in women developing GDM: 24.2 ng/ml

  • vs

  • Controls: 30.1 ng/ml (p<0.001)

  • [Difference remained significant after adjusting for weight, age, race, family history of DM, prepreg BMI]


Does vitd predict adverse preg outcomes

Does VitD predict adverse preg outcomes?

  • Meta-analysis up to Oct 2012

  • 24 studies fit criteria (Vitamin D/status/deficiency/insufficiency/pregnancy)

  • Outcome: women with VitD <50 nm/l:

  • OR 2.09 risk pre-eclampsia (CI: 1.5-2.9)

  • OR 1.38 risk GDM (1.12-1.7)

  • OR 1.57 risk preterm birth (1.08-2.31)

  • OR 1.52 risk SGA (1.08-2.15)

  • Wei .Mat-Fetal Medicine 2013.26.889


What about interventional studies

What about interventional studies?

  • ………..wait……………………


What links vitd and insulin resistance

What links VitD and insulin resistance?

  • 1. No one really knows

  • BUT

  • 2. Perhaps: through inflammation:

  • VitD can be shown to be associated with anti-inflammatory properties;

  • and insulin resistant states are also pro-inflammatory states

  • inflammationendothelialdysfunctionpre-eclampsia

  • inflammationimmune modulation (IL-1 and IL-6 in particular)


Links between vitd and insulin resistance

Links between VitD and insulin resistance

  • 3. Perhaps:

  • VitD receptors are present in the placenta and fetal tissues

  • VitD regulates genes involved in trophoblast invasion/angiogenesis


Links between vitd and insulin resistance1

Links between VitD and insulin resistance

  • 4. Perhaps:

  • pancreatic beta cells have VitD receptors

  • may regulate insulin secretion

  • Vit D stimulates insulin receptor expressionpromotes insulin sensitivity


Vitd and inflammatory markers

VitD and inflammatory markers

  • So:

    holding onto VitD considerations

    but

    switching over to thinking about adipocytokines


What are adipocytokines

What are Adipocytokines

  • Proteins produced by adipose cells

  • [note: adipose is not just unwanted insulation, but rather a large endocrine organ]

  • Many, many, many known and still unknown associations and effects


Adipocytokines

Adipocytokines

You know some of these already:

  • leptin

  • adiponectin

  • TNF-α

  • interleukins

  • resistin

    …etc….


Just a few metabolic associations of adipokines

Just a few metabolic associations of adipokines

  • Low adiponectin levels have been associated with an increased incidence of Type 2 DM

  • Adiponectin increased insulin sensitivity, fatty acid oxidation and reduces liver glucose production

  • Leptin reflects total body adipose mass

  • Resistin levels increase with fat mass and correlate with insulin resistance

  • TNFα and IL-6 increased in obesity and are linked to insulin resistance and type 2 DM


Functions of adipokines

Functions of Adipokines?

Endocrine; paracrine; autocrine roles in:

  • hemostasis

  • lipids metabolism

  • atherosclerosis

  • BP regulation

  • insulin sensitivity

  • angiogenesis

  • immunity

  • inflammation

  • Miehle. Clin Endocrinology 2012.76.2


Adipocytokines and gdm

Adipocytokines and GDM

  • TNF-α correlates with insulin resistance in pregnancy

  • TNF-α is released from maternal side of placenta

  • Leptin rises during pregnancy and falls after delivery

  • Leptin correlates with insulin resistance in pregnancy

  • Adiponectin levels are lower in GDM than control preg women

  • Lacroix. CurrDiab Rep 2013. 13. 238


For instance

For instance:


So cooking up a study in london on

..So, cooking up a study in London ON

INTERESTING UNKNOWNS:

  • What are VitD levels in offspring of GDM pregnancies?

  • What are the profiles of adipocytokines in GDM women AND their offspring?

  • Are maternal and neonatal VitD levels correlated?

  • Are maternal and neonatal adipokine levels correlated?

  • Do corralations exist between VitD and inflammatory adiokines (maternal and neonatal)?


We had the following building blocks

…..we had the following building blocks…


Psi grant

PSI grant

  • Maternal, umbilical arterial and umbilical venous 25 hydroxyvitamin D and adipocytokine concentrations in pregnancies with and without gestational diabetes

  • R McManus, K Summers, B DeVrijer, N Cohen, A Thompson, I Giroux Clinical Endocrinology 2014; 80:635-641.


Methods

Methods

  • Case control

  • GDM diagnosed before clinic referral

  • no recruitment during Nov-Mar months

  • GDM and Controls recruited at 31 weeks

  • Did 48 hour dietary and supplement recall [before GDM saw RD]


Methods1

Methods

  • Maternal blood taken/spun/frozen at 31 weeks for

  • Ca

  • Phosphate

  • BG

  • CRP

  • PTH

  • Adipocytokines (adiponectin, resistin, PAI-1, IL-6; Il-8, leptin, TNFα, MCP-1)


Methods2

Methods

  • On day of delivery:

  • Neonatal umbilical artery and umbilical vein bloods were taken for DR staff for:

  • Ca

  • Phosphate

  • BG

  • CRP

  • PTH

  • Adipocytokines (adiponectin, resistin, PAI-1, IL-6; Il-8, leptin, TNFα, MCP-1)


Do you want to guess

….do you want to guess?

Umbilical artery flows:

Umbilical vein flows:


Vitamin d adipocytokines

So

  • umbilical arterial blood would reflect fetal chemistry

  • umbilical vein blood would reflect maternal AND placental chemistry


Demographics

Demographics

Maternal

  • age

  • pre-pregnancy weight

  • maternal weight at time of blood taking

    Infant

  • birth weight

  • infant gestational age

  • apgar scores

  • duration of hospital stay/complications


A few stats

A few stats

Sample size of 24 X2=48 would allow for detecting a 30 nm/l difference between [VitD] in GDM women vs C


R esults

Results

  • 73 women

  • 36 GDM; 37 C

  • Matched for week of gestation; present weight; pre-preg weight; maternal VitD intake


Searching for correlations

Searching for correlations

[we limited correlations to r>0.4 or r<-0.4; p<0.05]

  • Maternal Control VitD levels: + correlated with resistin only

  • Maternal GDM VitD: + correlated with PAI-1; IL-8; TNF-α


Searching for correlations cont

Searching for Correlations..cont

  • Neonatal VitD levels were not correlated with any of:

  • infant weight

  • placental weight

  • Apgar scores

  • labour duration/hospital stay

  • adipocytokines


Admitting our limitations

Admitting our limitations

  • Big picture: no one knows what level of VitD is “ideal” for the non-osteomalacial actions of VitD

  • Our women were not as VitD deficient as in some studies so differing conclusions might occur if there was a wider range of serum levels

  • Our GDM women were generally only mildly hyperglycemic (ie) no one was on insulin when maternal bloods were taken: again a wider range of insulin impairement may have uncovered differing results


So what

So…what…?

#1: As expected:

  • GDM women had lower adiponectin than Controls

  • however, this finding was present despite being matched for weight and pregnancy week

  • lower adiponectin levels would be consistent with increased GDM maternal inflammation…but….


So what 2

So what #2

  • GDM had lower resistin and PAI-1 levels [argues against inflammatory biochemical profile]

  • GDM leptin was not different from C

  • GDM CRP, ILs, TNFα, MCP-1 not different as well

  • overall, no conclusive evidence for inflammatory chemistry in GDM women


So what 3

So what #3:

  • GDM maternal VitD lower than Controls

  • But:

  • Umbilical arterial and venous VitD showed no difference between GDM and C offspring


So what 4

So what #4

  • Maternal GDM VitD levels were positively (not negatively as expected) correlated with some adipokines thought to be associated with inflammation (PAI-1; IL-8, TNFα)

  • Neonatal VitD levels did not correlate with inflammatory markers


So what 5

So what #5

  • Neonates born to mothers with GDM also manifested lower adiponectin and resistin levels

  • even in umbilical arterial bloods

  • suggesting that there are adverse adipokine profiles present at birth


So what 6

So what #6

  • We learned a very important life lesson:

  • Never ever again do a study where blood samples from babies have to be centrifuged and frozen at any time of day, night, holidays……


Just an aside

Just an aside

  • Enthusiasm for VitD as THE miracle metabolic hormone has waned

  • Much of what our study was built upon (remember, grant applied for <2008) tantalizing hints and correlations around VitD effects

  • However, interventional studies have suggested perhaps some effect attributable to VitD, although final word not yet in…..


For instance1

For instance

  • 54 women with GDM (Iran)

  • randomized to placebo or cholecalciferol 50,000 u at study entry and day 21

  • fasting samples for BG and insulin taken at study onset as well as after 6 weeks


Vitamin d adipocytokines

  • Results:

  • VitD supplementation:

  • was correlated with lower FG

    (-17.1±14.8 mg/dl vs -0.9±16.6 mg/dl, p<0.001)

  • was correlated with lower serum insulin

  • was correlated with improved QUICKI index

    Asemi. Am J ClinNutr 2013.98.1425


One more

one more…

  • 120 Iranian women <12 weeks of pregnancy

  • randomized to:

  • 200 u VitD OD;

  • 50,000 u VitD monthly

  • 50,000 u Vit D Q2 weeks

    until delivery


Measured

measured:

  • FBG,

  • insulin,

  • Ca,

  • VitD

  • before and after intervention


R esults1

Results

  • Group C receiving 50,000 u every 2 weeks had biggest rise in VitD level

  • FBG dropped 2.02 mg/dl in Group C (NS)

  • Insulin level in group C went up less than Group A (NS)

  • comparing all 3 groups: insulin and HOMA IR were improved with higher doses of VitD supplementation

  • SoheilyhkhahGynecEndocrinol 2013. 29. 396


One last london connection

..one last London connection

  • DALI study

  • Vitamin D and lifestyle intervention for gestational diabetes mellitus (GDM) prevention: an European multicentre, randomized trial-study protocol

  • 9 countries

  • <20 weeks gestation

  • 8 intervention arms (placebo, healthy diet, healthy activity, Vit D combos)


Vitamin d adipocytokines

DALI

  • Vit D dose is 1600 u OD until delivery

  • primary outcome: gestational weight gain, fasting glucose and insulin sensitivity, OB outcomes

  • [biorepository blood is being stored at Lawson/David Hill]

  • Jelsma BMC Pregnancy Childbirth 2013. 13.124


That s all

that’s all ….


  • Login