Changes in amniotic fluid glucose, beta-hydroxy-butyrate, glycerol, and lactate concentration in diabetic pregnancy

Amniotic fluid glucose, beta OH butyrate, glycerol, and lactate concentrations were measured in 75 samples collected in the third trimester of pregnancy from 50 diabetic patients, all but four of whom required insulin. Increases in maternal fasting plasma sugar were accompanied by corresponding increases in amniotic fluid glucose and on occasion increases in amniotic fluid beta OH butyrate. These data correspond to previous reports of placental glucose transfer and in addition, provide statistically significant evidence of placental betaOH butyrate transfer since the hyperglycemic, hyperinsulinemic fetus of a diabetic mother would be a poor primary source for ketogenesis. Relatively poor correlation of elevated fluid levels of these solutes to fetal outcome probably reflects a low incidence of maternal hyperglycemia, ketogenesis. Relatively poor correlation of elevated fluid levels of these solutes to fetal outcome probably reflects a low incidence of maternal hyperglycemia, ketoacidosis, and over-all reduced neonatal morbidity-mortality rates in this group of metabolically well-controlled, predominantly insulin-requiring diabetic patients managed in a regional high-risk perinatal center.     

Effects of maternal glucose loading on brain energy metabolism of fetal rats during hypoxia and recovery

The effect of maternal infusions of hypertonic glucose on fetal brain carbohydrate metabolisms was investigated during the state of induced fetal hypoxia and its recovery using Wistar rats. Three milliliters of 20% glucose was injected into the pregnant rats and then the fetuses were delivered by hysterotomy after 20 minutes of induced hypoxia. The concentrations of glucose, lactate, ATP, ADP, AMP in fetal brain, and the levels of glucose and lactate in fetal blood were measured. The brain glucose concentrations in the loaded group was 3.9 times higher than that in the non-loaded group, and it decreased during hypoxia in both groups followed by a gradual increase in the recovery phase. Brain lactate levels were elevated during hypoxia in both groups, but the difference in the lactate levels was slight compared with the difference in the brain glucose levels in both groups. Brain ATP decreased by 21% in the glucose loaded group but 70% in the non-loaded group after hypoxia. The calculated brain energy charge potential [(ATP) + 0.5(ADP)]/[(ATP) + (ADP) + (AMP)] after hypoxia was 0.59 in the loaded group and 0.37 in the non-loaded group. This shows a high energy state in the brain of the glucose loaded group. It may be suggested that maternal glucose administration before and during fetal hypoxia does not cause remarkable lactate accumulation in the fetal brain, but serves to maintain a high intracellular energy state in the brain.     

Fetal beta cell function in diabetic pregnancy. Amniotic fluid concentrations of proinsulin, insulin, and C-peptide during the last trimester of pregnancy

Proinsulin, insulin C-peptide, insulin-binding antibody, and glucose concentrations were measured in amniotic fluid samples from 43 insulin-treated diabetic patients and 17 nondiabetic control patients between the thirty-six and thirty-ninth weeks of gestation. Insulin-binding antibodies in amniotic fluid were present in only three diabetic patients, although antibodies in maternal serum were found in 22 of the diabetic subjects. In the diabetic group, maternal serum insulin-binding antibodies were statistically unrelated to levels of C-peptide in amniotic fluid. The mean amniotic fluid concentrations of proinsulin (0.07 nmole/L), insulin (0.08 nmole/L), C-peptide (1.17 nmoles/L), and glucose (2.09 mmoles/L) were markedly elevated (p less than 0.001) in diabetic patients, as compared to nondiabetic control patients, thus suggesting exaggerated fetal beta cell function. C-peptide was correlated to both insulin (r = 0.69) and proinsulin (r = 0.35) in the diabetic group only. Infant birth weight and amniotic fluid C-peptide was significantly correlated in both the control group (r = 0.54) and the diabetic group (r = 0.38). Diabetic pregnancies associated with neonatal morbidity (n = 25) had significantly higher mean amniotic fluid concentrations of both insulin and C-peptide than did pregnancies without neonatal morbidity (n = 18). The amniotic fluid values of C-peptide and insulin in these latter two subgroups were overlapping and, therefore, could not serve to predict neonatal outcome in the individual case.     

Metabolic and circulatory effects of oral salbutamol in the third trimester of pregnancy in diabetic and non-diabetic women

Metabolic and cardiovascular effects of 4 mg oral salbutamol were studied in ten non-diabetic, ten chemical diabetic and five juvenile diabetic women in late pregnancy. None of the women had been treated with beta-sympathomimetic drugs earlier in their pregnancy. Heart rate and blood pressure were recorded and blood samples for measurement of plasma cyclic AMP, insulin, C-peptide, glucose, lactate, glycerol, non-esterified fatty acids (NEFA) and 3-hydroxybutyrate (3-HB) were collected every 30 minutes for 120 minutes after salbutamol. All women underwent the same procedure at random without salbutamol. There were significant cardiovascular effects of salbutamol in all the groups but no differences in these effects between the groups. Salbutamol caused significant increases of glycogenolysis and lipolysis in all the groups, significantly larger in the juvenile diabetic than the non-diabetic and chemical diabetic women. This observation could be explained by the inability of the juvenile diabetics to secrete insulin, shown by their non-measureable plasma C-peptide levels. The metabolic responses following salbutamol in the chemical diabetics were intermediate between the non-diabetic and juvenile diabetic groups. The results show that diabetes does not alter the sensitivity of beta-receptors involved in cardiovascular regulation, while the metabolic responses to oral salbutamol are enhanced, especially in juvenile diabetics. We suggest that during treatment with beta-sympathomimetic drugs, blood glucose should be monitored in all patients showing criteria of potential diabetes.     

The effect of diabetes on ovaries in a rat model: the role of interleukin-33 and apoptosis

Interleukin-33 (IL-33) is a novel cytokine involved in diabetes mellitus (DM) but its role in diabetic ovarian injury is unknown. As IL-33 is modulated by apoptosis, we aimed at investigating the effect of diabetes on ovaries in terms of evaluating apoptosis and IL-33 in a rat model. In this prospective experimental study, 16 female, nonpregnant Sprague–Dawley albino rats (12?weeks, 220–240?g) were randomly divided into two groups. Group 1 included eight healthy nondiabetic rats as controls and group 2 included eight rats in which diabetes was induced by intraperitoneal (i.p) injection of streptozotocin (STZ). After overt DM occurred (blood glucose >400?mgr/dl), all animals were euthanized and blood samples were collected by cardiac puncture for biochemical analysis. Bilateral oophorectomy was performed for histopathological examination. Serum levels of IL-33 and ovarian IL-33 and caspase-3 immunoexpressions were assessed. Immunoexpressions of caspase-3 and IL-33 were significantly higher in ovarian stromal cells of the diabetic rats compared to the controls. Also, in diabetic group, serum IL33 levels were significantly higher than the control group. In conclusion, increased IL-33 was observed both in serum and ovaries of STZ-induced diabetic rats as well as increased apoptosis in these diabetic rats. IL-33 may contribute to the apoptosis in diabetic ovarian injury.     

Insulin-induced hypoglycaemia in diabetic women during late pregnancy and one year post partum

Insulin (0.1 IW/kg) later followed by glucose was injected intravenously in nine diabetic women in the supine position both during pregnancy and one year post partum. C-peptide was present in five subjects, indicating some residual beta-cell function. Their mean basal C-peptide level, before insulin, was twice as high in the pregnant as inthe non-pregnant state. C-peptide decreased progressively after insulin. The mean basal plasma glucose level was lower during pregnancy (4.8 mmol/l) than after it (9.6 mmol/l), but decreased to the same level (2.2 mmol/l) after insulin. The rate of fall in glucose was thus lower during pregnancy (kt = 2.54) than after (kt = 4.08), but was unrelated to the basal glucose levels. Basal levels of free fatty acids (FFA), 3-hydroxybutyrate (3-HB), cyclic AMP, and lactate were similar, while glycerol was lower during pregnancy. Insulin-induced changes in FFA, glycerol, 3-HB, cyclic AMP, and lactate were similar during and after pregnancy. Plasma amino acid concentrations were generally lower in pregnancy, significantly so only for arginine and glycine. Amino acid levels were unaffected by insulin in pregnancy, whereas leucine, isoleucine and tyrosine decreased significantly in the non-pregnancy, whereas leucine, isoleucine and tyrosine decreased significantly in the non-pregnancy, whereas leucine, isoleucine and tyrosine decreased significantly in the non-pregnancy state. We conclude that there are differences in metabolic responses to insulin in diabetic women during and after pregnancy, indicating a decreased sensitivity to insulin during pregnancy in some tissues.     

Effect of maternal hyperketonemia in hyperglycemic pregnant ewes and their fetuses

The fetus of the pregnant diabetic woman is exposed to hyperglycemia frequently accompanied by ketoacidosis. Previous studies have demonstrated that beta-hydroxybutyrate, a major ketone body, crosses the ovine placenta in significant amounts, leading to significant reductions in fetal PaO2 and increased fetal heart rate. In the present study the pregnant ewe was used to evaluate the maternal and fetal cardiovascular and metabolic responses to hyperketonemia in the presence of hyperglycemia and to determine if the combined diabetic insults were more detrimental to the fetus than hyperketonemia alone. A glucose priming dose of 25 gm was administered in the maternal femoral vein followed by a continuous glucose infusion of 200 mg/min to achieve steady maternal plasma glucose levels of 180 mg/dl. Once glucose levels were stable, beta-hydroxybutyrate was infused for 2 hours at a rate of 0.39 mmol/100 ml of uterine blood flow into both left and right uterine arteries. Infusion of glucose alone did not significantly alter fetal cardiovascular and blood gas parameters but did increase the fetal glucose level from 17 +/- 4 to 58 +/- 8 mg/dl. The simultaneous infusion of beta-hydroxybutyrate and glucose produced significant decreases in fetal PaO2 and oxygen content as were reported for hyperketonemia alone and significant time-related increases in fetal lactate levels and fetal heart rate. These data suggest that hyperketonemia in the pregnant ewe leads to quantitatively similar changes in oxygenation in both normoglycemic and hyperglycemic fetuses. These observations may in part help explain the increased perinatal mortality in the pregnant woman with uncontrolled diabetes.     

Effects of intravenous ritodrine on lactate and pyruvate levels: role of glycemia and anaerobiosis

The role of glycemia in ritodrine-induced hyperlactatemia was assessed by measuring lactate and pyruvate levels and studying glycemia in patients treated with intravenous ritodrine for premature labor. Lactate levels were increased moderately by ritodrine and paralleled the levels of glucose; a similar parallelism also was observed in the glucose-administration group. Pyruvate levels also changed in proportion to lactate levels in this latter group, whereas in patients given ritodrine, pyruvate changed little and the lactate/pyruvate ratio was increased. These findings are discussed in terms of possible metabolic and vasopressor consequences of beta-adrenergic stimulation, with emphasis on the potential roles of increased glycemia and anaerobiosis.     

Effects of alloxan-induced diabetes mellitus on the metabolism of the rat placenta

Biochemical changes in the placenta were studied using alloxan-induced diabetes mellitus in the female rat. In comparison with a control group (n = 13) the placentas of the diabetic animals (n = 12) had significantly higher glucose, glycogen and protein levels. It was, however, shown that this supply of substrate was inadequately utilised for energy, as ATP/ADP quotient was lower and the ADP content was significantly higher. Metabolism still appeared to take place under aerobic conditions, as evidenced by the unchanged lactate levels. In terms of the protein content of the placentas, the activity of the enzymes we investigated (GOT, GPT, LDH, G-6-PDH, MDH, ICDH) was lowered by 25-44%. These results support the idea of global placental insufficiency in diabetics.     

The relation between pregnancy specific beta 1 glycoprotein (SP1) levels and abnormal glucose tolerance in pregnancy.

Pregnancy specific beta 1 glycoprotein (SP1) levels were measured in 54 potentially diabetic patients in the third trimester of pregnancy using a laser nephelometric method. All patients were tested by the 50 g oral glucose tolerance test. The results show that a significantly greater number of patients with abnormal glucose tolerance had SP1 levels above the mean compared with patients with normal glucose responses. All patients with a diabetic type response had SP1 levels above the mean. There was no significant difference in SP1 levels in the fasting and two-hour plasma samples. The study suggests that patients with asymptomatic glucose intolerance in pregnancy have higher SP1 levels than patients with normal glucose tolerance. It is possible that one of the factors controlling the placental output of SP1 is the maternal blood glucose level.     

Metabolic control in diabetic pregnancy. Variations in plasma concentrations of glucose, free fatty acids, glycerol, ketone bodies, insulin, and human chorionic somatomammotropin during the last trimester.

Metabolic control was evaluated under standard conditions in pregnant gestational and insulin-dependent diabetic patients and control subjects from: (1) changes during an 8 hour period in blood glucose, free fatty acids (FFA), glycerol, ketone bodies, chorionic somatomammotropin (HCS), and insulin during the last trimester and (2) changes from weeks 32 to 40 in fasting blood glucose, FFA, glycerol, and ketone bodies. Mean glucose levels calculated from five daily analysis 28 days before delivery were determined in insulin-dependent and gestational diabetic patients (pregnancy glucose level). Group mean 8 hour glucose levels were similar in diabetic patients and control subjects, but glucose swings were greater in diabetic patients. Gestational diabetic patients had delayed insulin response following meals. FFA, glycerol, and ketone bodies varied in parallel with a simmilar pattern in diabetic patients and control subjects. Insulin-dependent diabetic patients had suppressed lipid mobilization in the afternoon when glucose levels were almost normal. In control subjects, FFA, glycerol, and ketone bodies were not above normal nonpregnant values. Diabetic patients showed great individual variations in all parameters measured. FFA and ketone bodies were significantly above normal; glycerol and glucose were normal. Pregnancy glucose levels were significantly correlated to a mean amplitude of glycemic swings (MAGE) determined from the 8 hour glucose profiles. The glucose value 2 hours after breakfast correlated best to the MAGE value.     

A prospective controlled study of neonatal morbidities in infants born at 36 weeks or more gestation to Women with diet-controlled gestational diabetes (GDM-class Al).

OBJECTIVE: Infants of gestational diabetes mellitus (GDM)-A1 women are unlikely to experience the marked excursion in maternal glucose levels that may characterize insulin-requiring GDM (class-A2) or insulin-dependent diabetes (IDDM). However, infants born to GDM-A1 women are traditionally managed like infants born to GDM-A2 or IDDM women. AIMS: To examine monitoring protocols for infants of GDM-A1 women, and to examine the efficacy of early and frequent feedings to prevent and to treat hypoglycemia. METHODS: A total of 92 of 101 infants born to GDM-A1 women (diabetic group) and 68 of 83 infants born to nondiabetic women (control group) at > or=36 weeks of gestation were prospectively monitored for the development of hypoglycemia and other morbidities. Blood glucose screening was performed in the diabetic group every 30-60 minutes three times, starting soon after birth and then at 3-hour intervals for 24 hours. Liberal feedings were started shortly after birth and provided every 3 hours for at least 24 hours. All women with GDM-A1 had an HbA1c measured before delivery. RESULTS: Both the diabetic and control groups had similar demographics, including LGA incidence. Blood glucose readings before feedings were low (<40 mg/dl) in 24 of 92 infants (26.1%) from the diabetic group and in 20 of 68 control infants (29%). After the start of oral feedings, all but four diabetic and three control infants had subsequent glucose readings > or =40 mg/dl. No infant had symptoms of hypoglycemia and none from the diabetic group had birth trauma, hypoxic-ischemic encephalopathy, polycythemia, hypocalcemia, or hypomagnesemia. Hypoglycemic episodes in the infants from the diabetic group could be managed with oral feedings alone. Birth weight, gestational age, sex, Apgar scores, and maternal HbA1c levels could not predict low glucose readings on initial screening in infants from the diabetic group. CONCLUSION: The incidence of hypoglycemia in infants born to GDM-A1 women at > or =36 weeks of gestation is similar to control infants born to nondiabetic women. Low blood glucose levels during the first few hours of life can be prevented or treated with early and frequent oral feeding.     

Postprandial walking exercise in pregnant insulin-dependent (type I) diabetic women: reduction of plasma lipid levels but absence of a significant effect on glycemic control

In this study 42 pregnant women with type I diabetes and 28 nondiabetic controls were recruited to participate in a postprandial walking exercise program. Exercise patients were instructed to walk 20 minutes (1 mile) after each meal and were divided into two groups: group 1 were normal nondiabetic controls and group 2 were women with type I diabetes. There were two nonexercise comparison groups: group 3, nondiabetic controls, and group 4, women with type I diabetes. Diabetic women were followed weekly in an intensive perinatal program. Glycemic control was assessed by serial hemoglobin A1 concentration measurements, home blood glucose monitoring, 24-hour glucose profiles, and 24-hour quantitative urinary glucose loss. Glycemic control was modestly but not significantly superior in the diabetic exercise group 2 compared with the diabetic nonexercise group 4. Exercise was associated with lower fasting cholesterol and triglyceride values in both controls and diabetic women, with significantly lower fasting plasma triglyceride levels in the diabetic exercise group (p less than 0.02). There were no adverse effects of postprandial walking exercise in mothers or infants.     

Growth hormone response to clonidine in anovulatory infertile women resistant to clomiphene citrate stimulation

OBJECTIVE: To evaluate the GH response to the clonidine test in a group of infertile women and to determine their ovulatory response to clomiphene citrate (CC) stimulation. DESIGN: Prospective study. SETTING: Reproductive endocrinology unit. PATIENT(S): Thirty-three anovulatory infertile women (age range, 25-36 years) and 9 healthy controls with normal ovulation. INTERVENTION(S): In the early follicular phase, 0.3 mg of clonidine was administered between 8:30 and 9:00 A.M. and blood samples were collected for 120 minutes thereafter for measurement of serum GH levels. Plasma levels of insulin and glucose were measured after a 75-g glucose load, and CC was given at a dosage of 50-250 mg/d for ovulation-induction. MAIN OUTCOME MEASURE(S): Serum concentrations of GH, insulin-like growth factor I, insulin, and insulin-like growth factor binding protein-1. RESULT(S): On the basis of their ovulatory response to CC, 15 patients were considered nonresponsive (group 1) and 18 patients were considered responsive (group 2). Baseline levels of GH, insulin-like growth factor I, and insulin-like growth factor binding protein-1 were similar in the two groups of patients and the controls. The GH response to clonidine was significantly greater in group 2 and in the controls than in group 1. Concentrations of insulin and glucose after the glucose load were not different among the three groups. CONCLUSION(S): Women who were resistant to CC had a reduced GH response to clonidine. These data suggest that adequate GH secretory capacity is important for CC action.     

Threshold values of maternal blood glucose in early diabetic pregnancy--prediction of fetal malformations

BACKGROUND: The prevention of congenital malformations in the newborns of diabetic mothers still constitutes one of the main problems in this group of patients. AIM: The aim of this study was to analyze the prevalence of fetal malformations in diabetic pregnancies, as well as detection of the cut-off points for the first-trimester glycemia levels, relating to diabetes-induced fetal malformations. METHODS: The data for analysis were collected retrospectively from the case histories of diabetic pregnant women and their newborns, treated in our departments. For the evaluation of maternal diabetes control, the whole-day glycemia profiles as well as glycated hemoglobin (HbA1C) levels were registered. To establish the glucose cut-off values for malformations, we have used receiver operating characteristic (ROC) curves for fasting, 1-hr, and 2-hr postprandial glucose levels. To determine how metabolic control influences the risk of giving birth to a malformed infant, we followed 198 newborns of diabetic mothers and 4700 infants born of healthy mothers (control group). RESULTS: We detected malformations in the infants of 8.6% (n = 17) of diabetic mothers and 3.8% of the control (odds ratio: 2.35, 95% CI = 1.40-3.96). We compared this group of diabetic patients to another diabetic pregnancy group, analyzed over a period of 1988-93 (n = 209), in which 13 newborns (6.2%) manifested congenital malformations (odds ratio: 1.41, 95% CI = 0.67-2.99) (the difference was statistically insignificant). HbA1C level during organogenesis was not significantly higher in women whose infants were malformed. We proved, however, that the risk of malformations was higher, when HbA1C value exceeded 9.3%. The malformation rate in diabetes classes D-H (according to White) was higher than in classes B and C, but the difference was not significant. A wide spectrum of anomalies has been observed in the newborns of diabetic mothers. CONCLUSIONS: Our results confirm the view that diabetic pregnancy, despite the improved metabolic control, is still a strong risk factor for alterations in fetal development, particularly in patients with a tendency to brittle glycemia during first trimester of pregnancy. It seems that keeping fasting glucose levels in first trimester below 5.8 mmol/l and postprandial glucose levels below 9.1 mmol/l can contribute to decreasing number of fetal malformations in pregestational diabetes mellitus (PGDM) pregnancy. The ROC curves appear to be useful and adequate tool for the analysis of factors influencing fetal development in diabetic pregnancy.     

Relation between body composition, anthropometry, and glucose tolerance

Based upon the results of a 75 g oral glucose tolerance test, 305 subjects (157 men and 148 women), who were admitted to the National Cheng Kung University Hospital for health check-up, were divided into diabetic (n = 47, 25 men and 22 women), impaired glucose tolerance (IGT) (n = 53, 27 men and 26 women) and normal (n = 205, 105 men an 100 women) groups. All diabetics were of non-insulin-dependent diabetics. Body composition and anthropometries including body mass index (BMI), thickness of triceps skinfold (TSF), arm muscle circumference (AMC), and blood pressure were compared among these three groups. Body composition (percentage of fat, lean mass and total body water) was significantly correlated to BMI, TSF, AMC, blood pressure, blood glucose, hemoglobin Alc (HbAlc) and cholesterol. BMI was significantly correlated to blood pressure, blood glucose, HbAlc, triglyceride and serum glutamic pyruvic transaminase (SGPT) levels. TSF and AMC were not correlated to blood pressure, blood glucose, HbAlc or blood lipids. However, in defining adiposity, TSF seems more sensitive than BMI. The data of the IGT group did not show a significant difference from those of the normal group except for a higher systolic pressure and a 2-hour plasma glucose level after a 75 g oral glucose loading. The diabetic group showed significantly higher BMI, systolic pressure, triglyceride, and SGPT levels than both the IGT and normal groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison of the accuracy of glucose reflectance meters in pregnant insulin-dependent diabetics

Home monitoring of blood glucose by reflectance meters has been shown to be accurate in the nonpregnant diabetic and is currently used for outpatient glucose control in the pregnant diabetic as well. Beckman ASTRA glucose results from samples collected into sodium fluoride were used as the standard for this study. Comparisons were then made to four glucose reflectance meters: Accu-Check II, One Touch, DiaScan S, and ExacTech. Although the reflectance meters appeared to be useful for assessing blood glucose trends in the pregnant diabetic, the results obtained from these meters would be unacceptable in the laboratory setting. Unfortunately, because of the erratic combination of proportional and constant bias, correction factors are not easily ascertained. Laboratories and physicians should reconsider the use of these reflectance meters for inpatient evaluation and general population screening of pregnant women.     

Amino acid concentrations in maternal plasma and amniotic fluid in relation to fetal insulin secretion during the last trimester of pregnancy in gestational and type I diabetic women and women with small-for-gestational-age infants

Free amino acid concentrations were determined in maternal plasma and amniotic fluid (AF) under standardized and unstressed conditions in four groups of women comprising 6 gestational and 13 type I diabetics, 10 women with small-for-gestational-age (SGA) infants, and 18 healthy control women between 36 and 39 weeks of gestation. Plasma values for branched chain amino acids (the sum of leucine, isoleucine and valine) did not differ significantly between the four groups. The corresponding values in AF were significantly higher (P less than 0.05) in the type I diabetic group and significantly lower (P less than 0.05) in the gestational diabetic group as compared to the control group. The mean AF C-peptide concentration was elevated but not significantly so in gestational (0.69 nmol/l) or type I diabetic (0.54 nmol/l) pregnancies and significantly lower (P less than 0.05) in women with SGA infants (0.28 nmol/l) as compared to the control group (0.38 nmol/l). There was a significant correlation between C-peptide in AF and branched chain amino acids in maternal plasma (r = 0.63; P less than 0.05) as well as to maternal blood glucose (r = 0.79; P less than 0.01) in the type I diabetic group, which merely suggests a greater beta cell reactivity to insulin secretagogues in offspring of diabetic mothers. The correlation between AF C-peptide and branched chain amino acids in maternal plasma was significantly inverse in women with SGA infants (r = -0.75; P less than 0.05). Both individual, branched chain, or total amino acid concentration in AF were unrelated to AF C-peptide.     

Metabolomic biomarkers of impaired glucose tolerance and type 2 diabetes mellitus with a potential for risk stratification in women with polycystic ovary syndrome

There is a need to identify biomarkers of impaired glucose tolerance (IGT) and type 2 diabetes mellitus (T2DM) risk in women with PCOS to facilitate screening and the development of novel strategies to prevent disease progression. Metabolomic technologies may address this need. All published studies on metabolomic biomarkers of IGT and/or T2DM identified through MEDLINE (1966-December 2010), EMBASE (1980-December 2010) and Cochrane (1993-December 2010) were retrieved. Eligible studies were screened and specific study characteristics recorded including study design, number of participants, selection criteria, type of metabolomic technique used, site of sample collection, and a list of metabolites identified to have been altered in IGT and/or T2DM versus healthy controls was created.Nine metabolomic biomarkers that could potentially be used to identify women with PCOS at risk of developing IGT and/or T2DM were identified including leucine, isoleucine, citrate, glucose, creatinine, valine, glutamine, alanine and HDL. Of these biomarkers, a panel of four biomarkers were consistently either elevated or reduced including glucose (elevated), valine (reduced), HDL (reduced) and alanine (reduced) in IGT/T2DM compared with controls. These biomarkers may predict the development of IGT/T2DM in young women with PCOS. More studies are required to test this hypothesis and translate the findings into patient benefit by reducing the morbidity/mortality associated with IGT/T2DM in PCOS.     

Effect of pregnancy on glucose metabolism in glucose intolerant 'BB' Wistar rats

Little is known about the effect of pregnancy on the 'BB' Wistar rat, an animal model of insulin-dependent (type I) diabetes. The pathogenesis of diabetes in this animal model seems to result from antibody-mediated natural killer cell destruction of pancreatic beta cells. The glucose metabolism of glucose intolerant female rats (study group) was studied prior to pregnancy, during pregnancy, and postpartum using glucose tolerance tests (GTT). Control rats with normal GTT were studied and bred in a fashion similar to the study animals. Before becoming pregnant, the GTT levels of the chemically diabetic rats were significantly different from those of the controls (p less than 0.05). The GTT values of the study animals decreased during pregnancy to levels seen in pregnant controls. After pregnancy, the GTT values of the study animals returned to prepregnant levels. Based on these observations, it appears that pregnancy may block the autoimmune destruction of beta cells, causing an increase in insulin production and release, thereby improving glucose metabolism.