Effect of dietary fat and food consistency on gastroparesis symptoms in patients with gastroparesis.

BACKGROUND: Nutrition therapy for gastroparesis focuses on reducing meal size, fiber, fat intake, and increasing liquids intake relative to solid foods. Evidence to support these dietary interventions has been anecdotal. The aim of this study was to determine the effect of fat intake and solid/liquid meal consistency on symptoms in gastroparesis. METHODS: Twelve patients with gastroparesis were studied on four separate days receiving one of four meals each day in a randomized order: high-fat solid, high-fat liquid, low-fat liquid, and low-fat solid meal. At each visit, eight gastrointestinal symptoms were rated from 0 (none) to 4 (very severe) every 15 min, before and for 4 h after meal ingestion. KEY RESULTS: There was an increase in the total symptom score in the following order: high-fat solid > low-fat solid > high-fat liquid > low-fat liquid. For the high-fat solid meal, symptoms remained elevated throughout the 4 h postprandial period. Severity of nausea more than doubled after the high-fat solid meal, whereas the low-fat liquid meal caused the least increase in nausea. CONCLUSIONS & INFERENCES: A high-fat solid meal significantly increased overall symptoms among individuals with gastroparesis, whereas a low-fat liquid meal had the least effect. With respect to nausea, low-fat meals were better tolerated than high-fat meals, and liquid meals were better tolerated than solid meals. These data provide support for recommendations that low-fat and increased liquid content meals are best tolerated in patients with symptomatic gastroparesis.

Bodyweight in patients with idiopathic gastroparesis: roles of symptoms, caloric intake, physical activity, and body metabolism.

BACKGROUND: Most gastroparetic patients are underweight probably because of frequently experienced early satiety, nausea, and vomiting. Some gastroparesis (GP) patients, however, are overweight, for reasons that are not well understood. The aim of this study was to evaluate the factors that influence bodyweight such as resting energy and exercise-related expenditure, symptoms of early satiety, nausea and vomiting, and caloric intake in patients with idiopathic GP and in healthy controls. METHODS: Thirty-nine healthy controls and 29 subjects with idiopathic GP were studied. Resting energy expenditure (indirect calorimetry), body composition (bioelectrical impedance), dietary intake (Block Food Frequency Questionnaire), symptoms (Patient Assessment of Upper GI Symptoms), and physical activity (Paffenbarger exercise survey) were assessed. KEY RESULTS: Both median caloric intake (1242 vs 1804 kcal; p = 0.005) and caloric expenditure (486 vs 2172 kcal; p < 0.01) were significantly lower in patients with GP as compared to controls although BMI (25.8 ± 5.8 vs 24.3 ± 4.0 kg/m²) and resting energy expenditure (1327 ± 293 vs 1422 ± 243 kcal) were similar. On the other hand, the 12 GP patients who had gained weight (GW) since diagnosis had lower symptom severity (12.9 ± 4.4 vs 19.3 ± 6.3; p < 0.05), consumed more calories (1342 vs 1134 kcal; p = 0.08) and expended less calories for activity per week (406 vs 644 median kcal; p = 0.45) compared to the 17 GP patients who had lost weight or remained weight neutral (LW). CONCLUSIONS & INFERENCES: Patients with GP, although in energy balance, consumed and expended less calories than healthy controls. A subgroup of patients with GP who were less symptomatic, gained weight because of increased caloric intake and reduced energy expenditure.

A randomized comparison of a commercially available portion-controlled weight-loss intervention with a diabetes self-management education program.

OBJECTIVE: This study examined the efficacy of a commercially available, portion-controlled diet (PCD) on body weight and HbA1c over 6 months in obese patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: One-hundred participants with a mean±s.d. age of 55.6±10.6 year, body weight of 102.9±18.4 kg and HbA1c of 7.7±1.3% were randomly assigned to a 9-session group lifestyle intervention that included a PCD or to a 9-session group program of diabetes self-management education (DSME). Participants in the two groups were prescribed the same goals for energy intake (1250-1550 kcal per day) and physical activity (200 min per week). RESULTS: While both groups produced significant improvements in weight and HbA1c after 6 months of treatment, PCD participants lost 7.3 kg [95% confidence interval (CI): -5.8 to -8.8 kg], compared with 2.2 kg (95% CI: -0.7 to -3.7 kg) in the DSME group (P<0.0001). Significantly more PCD than DSME participants lost 5% of initial weight (54.0% vs 14.0%, P<0.0001) and 10% (26.0% vs 6.0%, P<0.0001). HbA1c declined by 0.7% (95% CI: -0.4 to -1.0%) in the PCD group, compared with 0.4% (95% CI: -0.1 to -0.7%) in DSME (P<0.026). Across both groups, larger weight losses were associated with greater reductions in HbA1c (r=0.52, P<0.0001). CONCLUSIONS: These findings demonstrate that a commercially available portion-controlled meal plan can induce clinically meaningful improvements in weight and glycemic control in obese individuals with type 2 diabetes. These data have implications for the management of obesity in primary care, as now provided by the Centers for Medicare and Medicaid Services.

Self-monitoring of blood glucose in gestational diabetes.

Numerous studies have clearly demonstrated a significant association between maternal glycemic control and adverse outcomes in pregnancies complicated by gestational diabetes. However, despite our understanding of the importance of stringent glucose control in the management of these pregnancies, the definition of optimal glycemic control and monitoring protocols have yet to be firmly established. This article reviews current evidence regarding the efficacy of self-monitoring of blood glucose in the management of gestational diabetes. The role of various self-monitoring protocols and their impact on outcome is also explored. Areas where further investigations are needed in terms of glucose assessment are highlighted.

One or two hours postprandial glucose measurements: are they the same?

OBJECTIVE: This study was undertaken to compare the rate of abnormal glucose levels measured after 1 hour (>140 mg%) with those measured after 2 hours (>120 mg%) postprandially in women with gestational diabetes mellitus (GDM). STUDY DESIGN: Sixty-eight women were included in this study. All had GDM based on the criteria of Carpenter-Coustan. Women with fasting glucose levels of 105 mg% or more were excluded from the study. All women were initially treated by diet. All women measured daily capillary blood glucose levels when fasting as well as 1 hour and 2 hours postprandially for 1 week, immediately after diagnosis of GDM. Glucose levels were obtained by memory-based glucometers. All women were followed in a specialized gestational-diabetes clinic throughout the pregnancy. Insulin therapy was started on an individual basis according to common clinical criteria. Epidemiologic and perinatal data were collected from medical charts. RESULTS: The average age of the women was 30.8 +/- 5.4 years. Thirty-five percent of participants were primipara. The mean gestational age at diagnosis was 28.8 +/- 5.4 weeks. Glucose measurements included 618 readings during fasting and 2730 either 1 hour or 2 hours postprandial. Rates of abnormal glucose (>95 mg% when fasting; >140 mg% 1 hour or >120 mg% 2 hours after each meal) per person were the following: fasting, 27.1% abnormal glucose measurements; postbreakfast, 22.4% abnormal levels after 1 and 8.5% after 2 hours (P < .01); postlunch, 16.4% abnormal levels after 1 hour and 18.2% after 2 hours (not significant); postdinner, 16.3% abnormal levels after 1 hour and 30.1% after 2 hours (P < .01). CONCLUSION: The rate of abnormal values was 2.5-fold greater 1 hour postbreakfast than 2 hours postbreakfast, in contrast to an opposite ratio of a 2-fold increase in the rate of abnormal values 2 hours postdinner versus 1 hour postdinner. Therefore, differential measurement (1 hour after breakfast and 2 hours after dinner) might impose stricter criteria for controlling blood glucose levels. Further clinical research should explore whether differential measurements might reduce the rate of diabetes-associated complications.

To screen or not to screen for gestational diabetes mellitus. The clinical quagmire.

Although there continues to be a lack of agreement about the most appropriate way to screen for GDM, screening remains the standard of care in this country. Universal screening of all pregnant women maximizes sensitivity but has significant financial implications because of its increased costs. Additional studies are needed that apply cost-analysis to various screening protocols to identify cost-effective screening strategies.

Fuel metabolism during pregnancy.

This article reviews carbohydrate and fat metabolism in both healthy pregnant women and women with gestational diabetes. Emphasis is placed on more recent investigations that have utilized stable, nonradioactive isotopes with insulin clamps to study gestational fuel metabolism. In early pregnancy, glucose-stimulated insulin secretion is increased, insulin sensitivity is unchanged or enhanced, and glucose tolerance is normal or slightly improved. Late gestation is characterized by accelerated fetal growth, rising concentrations of several diabetogenic hormones, and increased insulin resistance. The increased resistance reduces maternal glucose utilization, sparing carbohydrates for the rapidly growing fetus. The inhibitory effect of insulin on the rate of lipolysis is also significantly reduced during the third trimester of pregnancy. An earlier than normal switch from carbohydrate to fat utilization serves to promote the use of lipids as a maternal energy source. Women with gestational diabetes have been reported to have either comparable or increased insulin resistance during late gestation with several studies also demonstrating reduced insulin secretory capacity.

Effect of insulin on fat metabolism during and after normal pregnancy.

Whereas development of resistance to the action of insulin on glucose metabolism during gestation has been recognized, it is presently not known whether there is also resistance to the action of insulin on lipid metabolism. We have, therefore, examined the effect of physiological hyperinsulinemia (during euglycemic-hyperinsulinemic clamping) on free fatty acid (FFA) turnover in seven nondiabetic overweight or obese women during and after pregnancy. Basal rates of FFA release, oxidation, and reesterification and basal plasma FFA concentrations were not significantly different from each other during the 2nd and 3rd trimester of pregnancy and postpartum. During euglycemic-hyperinsulinemic (approximately 500 pmol/l) clamping, however, lipolysis was significantly less inhibited during the 3rd trimester (from 7.0 +/- 0.9 to 4.9 +/- 0.9 micromol x kg(-1) x min(-1), -30%) than during the 2nd trimester (from 8.4 +/- 0.6 to 4.1 +/- 0.9 micromol x kg(-1) x min(-1), -51%) and postpartum (from 8.5 +/- 1.1 to 4.2 +/- 0.6 micromol x kg(-1) x min(-1), -51%). Similarly, fat oxidation was not inhibited at all (from 3.5 +/- 0.3 to 3.8 +/- 0.5 micromol x kg(-1) x min(-1)) during the 3rd trimester but was suppressed by 51% (from 3.9 +/- 0.2 to 1.9 +/- 0.3 micromol x kg(-1) x min(-1)) during the 2nd trimester and by 38% (from 2.6 +/- 0.7 to 1.6 +/- 0.5 micromol x kg(-1) x min(-1) postpartum. These data demonstrated that resistance to the action of insulin on lipolysis and on fat oxidation developed during late gestation and disappeared postpartum.

Leptin in human pregnancy: the relationship with gestational hormones.

OBJECTIVES: The aims of the study were (1) to examine the relationship between leptin and placental hormones by measuring serial changes in serum levels of leptin during and after pregnancy and (2) to study the effects of several gestational hormones on leptin release from fully differentiated 3T3-L1 adipocyte cell cultures. STUDY DESIGN: Serum levels of leptin were measured throughout pregnancy and at 3 months post partum in 29 healthy women and were also measured in 18 healthy women at delivery by cesarean section and on postpartum day 3. In addition, 3T3-L1 mouse adipocytes were incubated for 24 hours in media containing various reproductive hormones and leptin production was measured. RESULTS: Serum leptin levels increased significantly (8.4 +/- 0.9 vs 13.5 +/- 1.5 ng/mL; P <.001) between the first 2 trimesters of pregnancy but not between the second and third trimesters. These changes in leptin did not correlate significantly with changes in body mass index. Leptin levels dropped significantly during the immediate postpartum period, from 34.1 +/- 4.9 at cesarean delivery to 7.3 +/- 1.4 ng/mL on postpartum day 3 (P <.001). Fasting insulin level did not correlate significantly with leptin level during pregnancy but did so during the postpartum period (r = 0.60; P <.05). Leptin secretion from 3T3-L1 adipocytes was increased significantly when cells were cultured with human chorionic gonadotropin (150%, P <.01) and also when they were cultured with estrogen (120%, P <.03). CONCLUSION: The data suggest that leptin production by adipose tissue is stimulated by several hormones of pregnancy, which may contribute to the increased leptin levels observed during gestation.

The role of free radicals and membrane lipids in diabetes-induced congenital malformations.

OBJECTIVE: The incidence of major congenital malformations is approximately 6-9% in pregnancies complicated by diabetes mellitus. This incidence is 3-4-fold higher than that in the general population. Congenital malformations are now ranked as the leading cause of death in the offspring of women with diabetes. The precise mechanism(s) by which these anomalies are induced is unknown. It is also not clear what predisposes women to deliver malformed infants, which infants are at risk, and why some are spared even when exposed to presumably high risk conditions. The purpose of this report is to determine, from the literature, the primary etiologic factors associated with diabetes-induced embryopathy and its prevention. METHODS: A review of the current literature regarding malformations in diabetic pregnancies was conducted to elucidate dominant concepts in the pathogenic mechanism(s) of these anomalies and to discuss current and future strategies for their prevention. RESULTS: Numerous investigators have demonstrated that hyperglycemia has a teratogenic effect during organogenesis. However, the exact mechanisms involved have not been completely elucidated. Dietary supplementation of deficient substrates (arachidonic acid or myo-inositol), either in vitro or in vivo, has been shown to reduce the incidence of diabetes-related malformations in offspring of diabetic pregnant animals. In addition, free oxygen radical-scavenging enzymes and antioxidants aimed at reducing the excess load of radicals also result in a reduced malformation rate. Clinical evidence has demonstrated that the teratogenic effects of hyperglycemia may be obviated by maintaining euglycemia throughout organogenesis. Numerous studies have demonstrated that participation in a preconception care program can reduce the incidence of malformations in women with diabetes to the background rate. Unfortunately, less than 10% of women with diabetes currently enter these programs. CONCLUSIONS: Diabetic embryopathy remains the single most common lethal problem affecting diabetic pregnancies today. Although preconception planning and glycemic control can reduce the incidence of malformations, it is often difficult to get women to attend such programs and to achieve and maintain euglycemia. The use of dietary supplements, which presumably would override the teratogenic effects of aberrant metabolic fuels, holds great promise for the future as a prophylaxis against diabetic embryopathy.

Is self-monitoring of blood glucose necessary in the management of gestational diabetes mellitus?

There continues to be controversy regarding the role of blood glucose in the management of pregnant women with gestational diabetes mellitus (GDM), specifically with regard to the use of capillary versus venous samples, as well as the frequency and timing of blood glucose determinations. At the Third International Workshop Conference it was noted that "self-monitoring of capillary blood glucose has been useful in allowing the woman to participate in her own management," but its utility "in the mild GDM not requiring insulin, although reasonable and logical, has not been formally proved." This article reviews the existing evidence in the literature regarding the impact of self-monitoring of blood glucose on outcomes in pregnancies complicated by gestational diabetes. Data regarding the optimal timing, accuracy, costs, and psychosocial effects of self-monitored glucose determinations will also be explored.

Free fatty acids and insulin resistance during pregnancy.

The purpose of this study was to determine whether elevation of plasma free fatty acids (FFA) in early pregnancy would cause alterations in insulin-stimulated glucose disposal similar to those occurring in late gestation. Seven glucose-tolerant women underwent 4-h euglycemic hyperinsulinemic (1 mU/kg.min) clamping during the early second trimester of pregnancy (14-17 weeks) on 2 consecutive days, receiving either lipid (Liposyn II; 1.5 mL/min) and heparin (0.4 U/kg.min; L/H) or saline/glycerol (2.25 g/h; S/G) infusions. Rates of total body glucose disposal (6,6-2H2 glucose) and of carbohydrate and fat oxidation (indirect calorimetry) were determined at hourly intervals. Blood glucose was clamped at about 85 mg/dL. Plasma FFA increased from 290 +/- 50 to 1000 +/- 139 mumol/L during L/H infusion and decreased from 351 +/- 60 to 35 +/- 11 mumol/L during S/G infusion. L/H infusion inhibited insulin stimulation of total body glucose disposal by 28% compared with S/G infusion (from 6.7 +/- 0.7 to 4.9 +/- 0.6 mg/kg.min; P < 0.01). L/H infusion increased fat oxidation from 0.73 +/- 0.04 to 1.26 +/- 0.2 mg/kg.min (P < 0.05) and decreased carbohydrate oxidation from 2.0 +/- 0.2 to 1.6 +/- 0.2 mg/kg.min (P < 0.05). Endogenous glucose production decreased equally by approximately 70% during L/H and S/G infusions. These data showed that elevating plasma FFA levels during early pregnancy inhibits total body glucose uptake and oxidation. We conclude that elevation of plasma FFA can contribute to the peripheral insulin resistance commonly observed during late pregnancy.

Diabetes mellitus in pregnancy. What are the best treatment options?

Diabetes mellitus complicates somewhere between 1 and 20% of all pregnancies worldwide. Women with all types of diabetes, including type 1 (insulin-dependent) and type 2 (non-insulin-dependent) diabetes mellitus, and gestational diabetes mellitus, as well as their infants, are at increased risk for a number of different complications. However, achieving and maintaining euglycemia throughout gestation has been demonstrated to reduce the risk of adverse outcome for both the mother and her offspring. Traditional management approaches use a combination of diet, exercise, intensive insulin regimens and multiple self monitored blood glucose determinations. There are a number of newer agents available to treat diabetes mellitus; however, their safety in pregnancy has not been thoroughly tested. Although the oral hypoglycaemic drugs are not customarily used during gestation in most of the US and Europe they have had considerable use in South Africa. Animal and human studies of the teratogenic effects of these drugs have yielded conflicting data and it is difficult to distinguish between the teratogenic effects of poor maternal metabolic control and the agents themselves. This article also addresses the current state of the knowledge regarding the drug safety of a variety of medications for conditions, including hypertension and preterm labour, commonly encountered in the management of the pregnant women with diabetes mellitus.

Pregnancy outcomes among women with and without diabetic microvascular disease (White's classes B to FR) versus non-diabetic controls.

The objective of this paper is to evaluate the impact of contemporary management on the maternal and neonatal outcomes of pregnancies complicated by diabetes in women with microvascular disease versus women without microvascular disease. The study population consisted of two hundred and eighty-eight (288) pregnant women with pregestational diabetes and one hundred and fifty (150) healthy pregnant controls. Diabetic women were grouped according to the presence (n = 103) or absence of diabetic microvascular disease (n = 185). Data were collected regarding diabetes management, level of glycemic control, and the development of antenatal complications. Maternal and neonatal outcomes were compared among the three groups. Women in the diabetes groups were stratified according to mean blood glucose levels and glycosylated hemoglobin during each trimester. There was no significant difference found between the two diabetes groups in terms of preterm labor, polyhydramnios, pyelonephritis, and growth restriction. The only maternal complications that occurred with increased incidence among women with microvascular disease were acute hypertensive complications (51.6 vs. 32.9%; p<0.05). However, when the diabetes groups were compared to healthy controls, a significant difference was seen in all maternal and neonatal complications. Preterm delivery, polyhydramnios, and large-for-gestational-age (LGA) infants were associated with poor third-trimester metabolic control as compared with others in satisfactory metabolic controls: 30.8 vs. 11.4% for preterm delivery; 17.3 vs. 5.1% for polyhydramnios; 51.9 vs. 33.9% for LGA; p<0.05. Congenital malformations were associated with poor first-trimester glucose control (5.8 vs. 1.3% anomalies in well-controlled women). Furthermore, major congenital malformations were also significantly increased in the offspring of women with diabetic microvascular disease 6.8%, as compared to 1.69% in diabetic women without microvascular disease; p<0.01. The incidence of hypertensive complications did not differ between the two diabetic groups. Pregestational diabetic women with and without microvascular disease can be counseled to anticipate comparably favorable pregnancy outcomes, although maternal and neonatal complications may exceed that experienced by pregnant women without diabetes mellitus.

Longitudinal study of carbohydrate metabolism in healthy obese pregnant women.

OBJECTIVE: To longitudinally characterize changes in insulin sensitivity in obese women during and after pregnancy. RESEARCH DESIGN AND METHODS: Six glucose-tolerant obese women underwent a 4-h euglycemic-hyperinsulinemic (500-600 pmol/l) clamping during the second (22.5 +/- 2 weeks [mean +/- SD]) and third trimester (36.8 +/- 0.9) of pregnancy and again 15.6 +/- 1.4 weeks after delivery. Rates of total body glucose turnover (with [6.6-2H2]glucose) and oxidation (with indirect calorimetry) were measured. RESULTS: There were no significant changes with respect to the action of insulin on rates of glucose disappearance (GRd), carbohydrate oxidation, or endogenous glucose production (EGP), comparing the second trimester of pregnancy with the nonpregnant (postpartum) state. The third trimester, however, was characterized 1) by reductions in insulin-stimulated GRd (-28%, P < 0.05, compared with the second trimester and -40%, P < 0.05, compared with postpartum); 2) by even larger reductions in insulin-stimulated carbohydrate oxidation (-46%, P < 0.05, compared with the second trimester and -54%, P < 0.02, compared with postpartum); and 3) by reduction of insulin suppression of EGP (-39% compared with -79% at the second trimester and -77% postpartum, P < 0.01). CONCLUSIONS: Glucose-tolerant obese women developed peripheral was well as hepatic insulin resistance during the third trimester of pregnancy. These alterations were reversed after delivery and appeared to be adaptive mechanisms to cope with the increased demand for glucose of the growing fetus.

Leptin is present in human cord blood.

It has recently been reported that the ob gene receptor was expressed on human and murine hematopoietic stem cells and that the ob gene product leptin stimulated hemato- and lymphopoiesis at the stem cell level. These findings suggest a role for leptin in hemato- and lymphopoiesis during fetal development. There is at present no evidence, however, that leptin is synthesized and released by the fetus. To investigate this possibility, we have measured plasma leptin concentrations in the cord blood of 78 newborn infants. We found that leptin was present in all 78 infants in concentrations comparable with those found in adults (0.6-55.7 ng/ml). Overall, plasma leptin concentrations in the cord blood of infants correlated with birth weight (r = 0.74, P < 0.001). These observations show that leptin is synthesized and released by fetal fat cells. In addition, they are compatible with the concept that leptin may play a role in human fetal hematopoiesis.

Early fetal growth delay: is it really predictive of congenital anomalies in infants of diabetic women?

It has been reported that the congenital anomalies frequently observed in offspring of diabetic women may be predicted by first-trimester ultrasound findings that reveal diminution in growth of the embryo/fetus. The aim of the current study was to examine the relationship between early growth delay and congenital anomalies in pregnancies complicated by diabetes. We conducted a retrospective study of 38 patients with insulin-requiring pregestational diabetes mellitus and 81 control pregnancies who had first-trimester ultrasound examinations. A cross-sectional survey of all patients revealed a congenital anomaly rate of 18.4% among the diabetic pregnancies compared to 4.9% among controls (P < 0.02). Early fetal growth delay was defined as a difference of six or more days between the menstrual gestational age and the sonographic gestational age (menstrual age minus ultrasound age). Early growth delay was exhibited in fifteen control pregnancies (18.5%) and eleven insulin-requiring pregestational diabetic pregnancies (28.9%) (P = 0.02). However the incidence of congenital anomalies in these two groups was significantly different, but there was no difference between groups with and without growth delay. The longitudinal growth of two anomalous fetuses of the diabetic group and three anomalous fetuses from the control group was studied. Both groups of fetuses remained within the normal growth range for their respective groups. This study described herein fails to confirm the association of early fetal growth delay with the occurrence of congenital malformations in insulin-requiring pregestational diabetic pregnancies.