Lisa Marasco, MA, IBCLC, FILCA. LisaIBCLC@Marasco.US



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BREASTFEEDING ON THE INSULIN DYSREGULATION SPECTRUM Lisa Marasco, MA, IBCLC, FILCA LisaIBCLC@Marasco.US Learning Objectives: 1. Describe the pathway in which insulin regulates milk production through the stages of lactogenesis. 2. List 2 ways in which insulin resistance may negatively affect milk synthesis. 3. List at least two strategies for addressing low milk production related to insulin resistance. I. Normal Insulin Dynamics a. Metabolic Simple: Insulin binding affects glucose uptake Complex: Multiple pathways options triggered by insulin binding b. Breast Insulin plays a supportive role in pubertal mammary development Breast is relatively insulin resistant during pregnancy During pregnancy, insulin regulates the switch from proliferation to differentiation (Neville 2013) c. Lactation After delivery, breast becomes more insulin sensitive Lactogenic complex necessary for Lactogenesis II Lemay 2013- Insulin influences milk synthesis via PTPRF (protein tyrosine phosphatase, receptor type F) Insulin Lactogenesis II Prolactin Cortisol Lactogenic Complex RNA Sequencing of the Human Milk Fat Layer Transcriptome Reveals Distinct Gene Expression Profiles at Three Stages of Lactation. Lemay 2013

IDENTIFYING THE STAGES INSULIN NECESSARY FOR MILK PROTEIN SYNTHESIS PTPRF = protein tyrosine phosphatase, receptor type F MECHANISM FOR IMPACT OF IR ON MILK PRODUCTION

II. Type 1 Diabetes a. Inadequate insulin production to support normal glucose metabolism b. Poor control during pregnancy (Neubauer 1990) Lower prolactin levels Decreased thyroid hormones Decreased human placental Lactogen (HPL) mechanism to affect mammary growth? Onset of lactation ½-1 day longer than normal (Hartmann 2001) Breastfeed early and often to bring milk in sooner c. Postpartum impact (Neubauer 1990) Diabetic infants may display immature sucking patterns, impacting milk removal and stimulation of lactation (Bromiker 2006) Poor glucose control can result in fluctuations of milk synthesis Insulin requirements can be 25-50% less during lactation Mastitis and yeast infections more common in diabetic mothers with poor control Miyake 1989 Group Suckled mls Manually extracted mls Total mls Controls (40) 658 ± 87 446 ± 58 1105 ± 121 Ovulatory disturb (57) 510 ± 60 512 ± 52 1023 ± 103 Diabetes Mellitus (40) 364 ± 40 490 ± 64 853 ± 98 Hypo-thyroid (28) 435 ± 46 457 ± 61 892 ± 118 Hyper-thyroid (40) 578 ± 77 478 ± 71 1056 ± 170 III. Type 2 Diabetes / Gestational Diabetes a. Insulin receptor resistance reduces insulin binding, affecting glucose uptake Body starts overproducing insulin to compensate hyperinsulinemia Physical symptoms of insulin resistance (IR) include skin tags, acanthosis nigricans b. Breast development Hyperinsulinemia prior to puberty acts like growth hormone, may fuel excessive growth Hyperinsulinemia soon after puberty may reduce breast size via fueling of excessive androgens, which may suppress growth Insulin resistance could affect differentiation of the mammary gland during pregnancy

c. Lactation Higher risk of delayed onset of lactation (Matias 2014; Chapman 2014) GDM risk factors for problems: Obesity (AOR 1.56); insulin during pregnancy (AOR 3.11); Age increments of 5 yrs (AOR 1.05); LATCH score <7.5 Excessive weight gain: High BMI + excessive weight gain = additive risk (Hilson 2006) Duration of lactation diminishes with increasing severity of diabetes (Hummel 2008)

d. Long-term impact of breastfeeding on metabolic health Longer lactation associated with improved metabolic profiles (Gunderson 2007, 2012; Ram 2008.) Reverse causality? Metabolic profile affecting duration of lactation IV. Treatment Strategies: Address the underlying issue: insulin resistance (Nommsen-Rivers 2012) Level 1: Diet Smart foods for insulin resistance: Legumes garbanzo & kidney beans, brown rice, carob, cinnamon Reversing calorie intake at meals (Jakubowicz 2013) Nutrients that help insulin resistance: Magnesium, Chromium, Gymnema (Bindlish 2014) Level 2: Medications and Supplements 1. Metformin to improve insulin receptor sensitivity (Bargiota 2012) Improved insulin dynamics may help with milk synthesis Reduced insulin resistance slows androgen production, inhibition Treatment during pregnancy may set up for better start-up of lactation; reduces miscarriages, GD, pre-eclampsia, premature births (Glueck 2002, 2004) Impact on breast growth during pregnancy not yet validated (Vanky 2012) Note: Metformin can deplete B-12 2. Myo-inositol: The Second M (Larner 2010) Naturally occurring in foods (Clements, 1980) Inositol is a secondary messenger for insulin Myo- and D-chiro inositol signal different insulin pathways Myo-inositol converts via epimerization to D-chiro-inositol Insulin resistance frequently associated with imbalance of conversion 40:1 ratio of Myo-inositol to D-chiro-inositol appears to give best results in PCOS (Nordio 2012); more effective in obese women (Genazzani, 2012) Improves insulin sensitivity, glucose utilization; reduces free testosterone Virtually no side-effects No research on impact on lactation, but rationale same as for metformin

Inositol presentation: http://www.slideshare.net/lifecarecentre/what-is-40-1-in-management-of-dr-jyotiagarwal-dr-sharda-jain-dr-jyoti-bhaskar Level 3: Smart Galactogogue options (anti-diabetic properties) Goat s rue (precursor of metformin) Malunggay Blackseed Fenugreek Dandelion Nettle leaf Milk thistle Coriander seed Natural progression of prediabetes into diabetes: http://www.priorslegh.co.uk/diabetes/index.php/what-is-prediabetes Changing therapies to address diabetes progression: http://www.medscape.org/viewarticle/418591_9 Proactive option for better start to breastfeeding: Antenatal Expression: early stimulation of lactation, provides colostrum for newborn if hypoglycemia treatment is necessary or lactation is delayed (Forster 2011; Singh 2009)

SMART FOODS, SUPPLEMENTS AND HERBS FOR INSULIN-RESISTANT MOTHERS WITH LACTATION PROBLEMS Smart Foods for Insulin Resistance Legumes Garbanzo beans Kidney Beans Brown rice Cinnamon (½ tsp per day) Carob Powder Dietary supplements to reduce diabetes Gymnema Magnesium Myo- and D-chiro-inositol 40:1 Foods high in inositol Cantaloupe ¼, (355mg) Orange (307mg) Grapefruit, ½ (199mg) Eggplant ½ c, (84mg) Kiwi, ½ c (136mg) Cabbage, ½ c (70mg) Brussel sprouts ½ c (80mg) Kidney beans, canned, ½ c (249mg) English peas, canned, ½ c (235mg) Green beans, ½ c (105mg) Wax beans, ½ c (144mg) Stone-ground wheat bread, 1 slice (287mg) Northern beans, canned, ½ c (440mg) Northern beans, dried, ½ c (327mg) Nectarine (118mg) Foods high in chromium Orange Potatoes Broccoli Basil Garlic Red grapes Foods rich in magnesium Bananas Broccoli Artichokes Watermelon Avocados Raspberries Salmon Blue berries Maple syrup Smart herbal galactogogues for insulin resistance: Fenugreek Goat s Rue Dandelion leaf Nettle leaf Milk thistle Malunggay Coriander seed Black seed