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JIA LU DIETETIC INTERN

FRESNO STATE

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*History of diabetes and discovery of insulin *Effects of early and late stage hyperglycemia *Management of hyperglycemia *Summary

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* Hyperglycemia: Elevated blood sugar > 180 mg/dL * Hypoglycemia: Low blood sugar <70 ml/dL * Fetal Programming: The process where by a stimulus applied in
utero establishes a response in the fetus leading to enhanced susceptibility to disease.

* Gestation: Carrying of an embryo/fetus in mammals * Methylation: Adding an -CH3 group * Morphogenesis: Beginning to shape the process in which an
organism develops its shape.

* Nephrogenesis: Development of the kidney

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* DIABETES = Siphon
* MELLITUS = Honey/Sweet
* Gestational diabetes: Temporary diabetes that occurs during
pregnancy

* Aretaeus the Cappodacian

* Attempted to treat it with oils, dates, gruel * Early treatments: exercise, high fat/meat diets to high CHO diets

* Frederick Allen prescribed low calorie diets, as little as 450 calories * Frederick Banting and Dr. Charles Best discovered insulin

1st trimester 0-13 weeks

Face, eyes, organs, limbs, circulatory system, liver starts producing bile, finger prints

2nd trimester 14-26 weeks

Skeletal development, eyebrows, taste buds, hearing develops, alveoli in lungs, stores fat

3rd trimester 27 to 40 weeks

Ability to blink, skin smooth out, nails, hair. Period of weight gain

THEORY and GENETICS

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* Obesity and Maternal Diabetes: Increases the risk of diabetes.
* Diagnoses
of diabetes was almost exclusively found in children of mothers with diabetes. (<15 age)

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* Thirty
Gene hypothesis A genetic factor that suggests that during times of starvation the fetus adapts to the environment in order to preserve life

* 1970s

Freinkel Study Maternal hyperglycemia is an important determinant of obesity and diabetes.

* Pima Indians Study supported the findings

* Barker

et al pioneered the link between intrauterine environment and adult disease.

* Low

birth weight babies are at higher risk of metabolic disorders.

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Examines the biochemical changes DNA methylation and histone modifications, control the spatial, temporal and parent-specific expressed gene patterns
* The most studied epigenetic is
cystosine-phosphatidyl-guanine (CpG).

* Methylation of a region of CpG is

associated disease

* The degree of hypermethylation

is directly dependent on glucose levels

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* The most prevalent malformations of
diabetic pregnancies are genitourinary
and renal malformations.

* Two events in kidney development are

ureteric branching morphogenesis and
nephrogenesis.

* Hyperglycemia suggests reduces the

number of nephrons

* Renal malformations affects both male and

female

STZ = Streptozotocin. A naturally occuring chemical toxic to beta cells in the pancreas.

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* Exposure to to late-gestation hyperglycemia in utero environment
results in changes in cardiac function that persists into childhood.

* Males offspring of hyperglycemic mothers (OHM) had diminished

LV diastolic function

* Findings are similar to those found in neonatal period of human

infants of diabetic mothers

* Female OHM had decline in heart function * Males were unchanged, but had a shorten fraction period.

* Newborns >9 pounds due to excessive fat storage

* Shoulder dystocia * Neonatal Hypoglycemia

TREATMENT

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Anti-diabetic drug
Suppresses hyperglycemia, suppresses hepatic glucose output, increases insulin sensitivity, and enhances peripheral glucose uptake.

* Reduce the risk of CVD, improves lipid

panels, does not cause weight gain.

* Contraindicated for people with kidney

disorders/disease, lactic acid build up, lung and liver disease

* Long and rapid acting insulin helps control blood sugar * Women who need insulin supplemented had a higher fasting
glucose in the oral glucose tolerance test

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*Moderate in fat and protein *Portion controls, less than half kcals
from CHO

*High fiber *Vegetables 3-5 servings *2-4 servings of fruit

*Fetal programming is heavily influenced by hyperglycemia,

impacts organ development

*Puts the infant at risk for adult obesity

*Prevention?

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Literature: 1. Yajnik, CS. Intrauterine Programming of Diabetes. Diab. 2009;26(3):61-71 2. Agoudemos, A et al. Programming of Adult CVD Following Exposure to Late -Gestation Hyperglycemia. Neonatology 2011: 100:198:205 3. Hartling, L. PhD. Benefits and Harm of treating Gestational diabetes mellitus: A systemic review and metal analysis for the US preve ntion services task force and national institutes of health office of medical applications and research. Annals of Internal Medici ne. 2013, vol. 159, number 2. 4. Jansson, T et al. Role of the Placenta in Fetal Programming: Underlying mechanisms and Potential interventional approaches. The Bi ochemical Society: 2007.

5.Hokke, S. et al Altered Ureteric Branching Morphogenesis and Nephron Endowment in Offspring of Diabetic and Insulin -Treated Pregnancy. PlOS
One 8(3):e5843. Available on MedLine 6. Gui, J. et al. Metformin vs Insulin in the Management of GDM: A Meta-Analysis. PLoS One 8(5): e64585. Availble on MedLine. 7. Lehnen, H et Al. Epigenetics and GDM and offspring health: The time for action is in the early stages of life. The Euro Soc. Of H uman Health and Reproduction. 2013. Available on MedLine.
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