Acute Exercise Effects in Obese Pregnancy

Acute Effects of Aerobic and Resistance Exercise on Maternal Glucose Metabolism and Vascular Function in Obese Pregnancy

Obesity before and during pregnancy is associated with a higher risk for a number of obstetric and metabolic complications in women and their offspring. Of particular importance, obese women have a higher risk of developing gestational diabetes and preeclampsia. In addition, obese women have larger offspring who have a higher risk for the development of obesity and diabetes; both largely attributed to higher maternal glycemia and glucose intolerance during pregnancy. Thus, identifying rehabilitative interventions that improve maternal and offspring metabolic and cardiovascular health in obese pregnancy are critical and have immediate and generational impact. Resistance and aerobic exercise training is a clinical staple for improving musculoskeletal, metabolic and cardiovascular health in non-gravid adolescents and adults with obesity however little is known regarding the effects of exercise during obese pregnancy. This study proposes to collect preliminary data on the independent effects of acute aerobic and resistance rehabilitative exercise on glucose metabolism and vascular function during pregnancy in n=15 obese women in order to inform a large, multisite clinical trial examining the acute and chronic effects of aerobic and resistance exercise on glucose metabolism and vascular function in normal weight, overweight and obese women during pregnancy.

Maternal obesity prevalence is at a historic high with over 1 in 3 women entering pregnancy obese and 1 in 10 extremely obese. Obesity before and during pregnancy is associated with a higher risk for a number of obstetric and metabolic complications in women and their offspring. Of particular importance, obese women have a higher risk of developing gestational diabetes and preeclampsia. In addition, obese women have larger offspring who have a higher risk for the development of obesity and diabetes; both largely attributed to higher maternal glycemia and glucose intolerance during pregnancy. Thus, identifying rehabilitative interventions that improve maternal and offspring metabolic and cardiovascular health in obese pregnancy are critical and have immediate and generational impact. Resistance and aerobic exercise training is a clinical staple for improving musculoskeletal, metabolic and cardiovascular health in non-gravid adolescents and adults with obesity. Observational studies suggest that exercise in pregnancy is safe and higher levels of physical activity before and during pregnancy in normal weight (i.e. lean) women reduces the risk of gestational diabetes and gestational hypertensive disorders; however, little is known regarding the effects of exercise training during obese pregnancy and several important questions still exist. These include: 1) "What are the acute and chronic effects of maternal exercise on glucose metabolism and vascular function?", 2) "Are there different effects of aerobic and resistance type exercise on glucose metabolism and vascular function?" and 3) "What are the physiologic and molecular transducers of maternal aerobic and resistance exercise for changes in maternal glucose metabolism and vascular function during pregnancy?" This pilot project aims to collect preliminary data on these questions. This proposal would be the first study to collect preliminary data on the independent effects of acute aerobic and resistance rehabilitative exercise in pregnancy, and further, in obese women; a population with a high morbidity during gestation. In addition, this proposal would inform a large, multisite clinical trial examining the acute and chronic effects of aerobic and resistance exercise on glucose metabolism and vascular function in normal weight, overweight and obese women during pregnancy. Moreover, this proposal would provide initial evidence of molecular transducers of acute physical activity/rehabilitative exercise necessary for a large, comprehensive clinical trial examining the molecular transducers of rehabilitative exercise in normal weight, overweight and obese women during different stages of pregnancy. Specific Aim #1: To characterize the acute effects of aerobic and resistance exercise on glucose metabolism (tolerance, insulin sensitivity and β-cell function) in obese women during mid-pregnancy. Specific Aim #2: To characterize the acute effects of aerobic and resistance exercise on vascular function in obese women during mid-pregnancy. Specific Aim #3: To explore the molecular transducers of physiologic responses in glucose metabolism and vascular function following acute aerobic and resistance exercise in obese women during mid-pregnancy. The hypothesis is that acute aerobic and resistance rehabilitative exercise will improve post-exercise glucose metabolism and vascular function in obese women during mid-pregnancy. In a subsequent multi-site clinical trial, this study will examine differences in physiologic effects and molecular transducers of aerobic and resistance exercise on glucose metabolism and vascular function during different stages of pregnancy in overweight and obese women.

Single group crossover design of acute effects of resistance exercise, aerobic exercise or rest (control) on maternal vascular function and glucose metabolism

One acute exercise session of resistance exercise (40 minutes including 3 sets of 8-10 repetitions at the participant's 10 repetition maximum load of upper and lower extremity exercise

Oral Glucose Insulin Sensitivity (OGIS) during a 2-hour oral glucose tolerance test. OGIS (an acronym for Oral Glucose Insulin Sensitivity) is a method for the assessment of insulin sensitivity from the oral glucose tolerance test. OGIS provides an index which is analogous to the index of insulin sensitivity obtained from the glucose clamp. Mari, et al. OGIS uses modeling of glucose values at 0, 90, 120 min and insulin values at 0 and 90 min (2-h OGTT) to calculate the index. A model-based method for assessing insulin sensitivity from the oral glucose tolerance test. Diabetes Care 2001 Mar;24(3):539-48. The formula for OGIS is the following: (glucose clearance rate + square root(glucose clearance rate*glucose clearance rate + 4*pp5*pp6(glucose at 90 min-gcl)*330))/2. A calculation spreadsheet for OGIS is found at: http://webmet.pd.cnr.it/ogis/index.php

Augmentation index: reactive hyperemic response post-blood pressure cuff inflation. Reactive hyperemia is the transient increase in organ blood flow that occurs following a brief period of ischemia (e.g., arterial occlusion).

Inclusion Criteria: First trimester BMI ≥ 30.0 and <45.0 kg/m2 (calculated from clinical weight and height) Singleton gestation, between 23 weeks and 0/7 days and 28 weeks and 0/7 days Normal fetal anatomy (no major structural abnormalities identified on standard of care survey before enrollment) Established prenatal care at Women's Health Clinic before 18 weeks of gestation, plans to deliver at Barnes-Jewish Hospital Permission from Obstetrics physician provider to participate in study. Exclusion Criteria: Gestational or pre-gestational diabetes diagnosis Inability to provide voluntary consent Currently using illegal drugs (e.g., cocaine, methamphetamine, opiates) (safety risk and potential confounding) Current smoker who does not agree to stop (confounding) Participation in routine (>1x/week) exercise program (may improve glucose metabolism/vascular function) History of heart disease, orthopedic, metabolic or neurological condition that would contraindicate exercise (safety risk)