Calorie restriction for treatment of gestational diabetes.

Birth weights of infants of 35 gestational diabetic mothers treated with calorie restriction alone (1200-1800 kcal) were compared with those of infants of 2337 nondiabetic women, including two control groups (A and B) matched for race, body mass index, age, and parity. All women were screened for gestational diabetes with the O'Sullivan screening method, and a 3-h oral glucose tolerance test was performed on all abnormal results. Control group A mothers had a normal screen, and control group B mothers had an abnormal screen with a normal glucose tolerance test. Pregnancy weight gain was significantly less for the gestational diabetic mothers (mean +/- SD 4.6 +/- 4.9 kg) than for the general prenatal population (9.3 +/- 5.3 kg), group A control subjects (9.7 +/- 5.3 kg), and group B control subjects (9.7 +/- 5.4 kg; P less than 0.0005). No infant of a gestational diabetic mother was below the 10th percentile for weight, and birth weights were similar to those of the control groups even though weight gain after the 28th wk of gestation was only 1.7 +/- 1.6 kg. The frequency of macrosomia (birth weight greater than or equal to 4000 g) was similar among the gestational diabetic mothers (9.3%), the general prenatal population (7.4%), and group A mothers (11.6%) but significantly higher for the group B control subjects (20.9%; chi 2 = 8.57, P less than 0.005). This study demonstrated that gestational diabetic mothers who are calorie restricted have infants with normal birth weights and a frequency of macrosomia less than that of screen-positive nondiabetic women with similar macrosomic risk factors.

Estimation of cholesterol in bile: assessment of an enzymatic method.

Cholesterol in bile has been estimated using two variants of the cholesterol oxidase method and compared with gas-liquid chromatographic (GLC) assay. As published, the enzymatic method seriously underestimated biliary cholesterol. This was due to interference by other constituents of bile, particularly bilirubin and lecithin. However, by dilution of reagents and samples in water and isopropanol respectively a close correlation with the GLC method is achieved. It is concluded that the cholesterol oxidase method as published is unsuitable for the estimation of cholesterol in bile, but in modified form it is simple, accurate and economical.

Reversal of diabetic related accelerated fetal growth by maternal glycaemic control.

In a young woman with insulin-dependent diabetes mellitus, poor diabetic control during the second trimester of pregnancy resulted in ketoacidosis, accelerated fetal growth and polyhydramnios. With the establishment of tight maternal glycaemic control, both accelerated intrauterine growth and polyhydramnios were reversed and a good pregnancy outcome resulted.

Diabetes and diet in pregnancy.

The mean additional energy requirement for pregnancy has been calculated at 285 kcal daily and it reflects the energy needs for production of the fetoplacental unit and for the maternal physiological adaptations to pregnancy. In practice there is considerable variation in energy requirement due to alterations in maternal energy expenditure. Optimal energy intakes are dictated also by the pre-pregnancy maternal weight. The outcome of pregnancy is improved in the underweight mother by an intake which produces a weight gain in pregnancy of approximately 14 kg, whereas a rise of only 7 kg may be optimal for the obese mother. Obesity with or without diabetes is associated with macrosomia and other problems and it is sensible to attempt to limit weight gain in pregnancy at a time when maternal motivation is high. Diabetes in pregnancy may arise in patients with pre-existing NIDDM or IDDM, but more commonly it is diagnosed for the first time during pregnancy and it usually disappears after delivery (gestational diabetes). Recent evidence suggests that gestational diabetes has a strong genetic component and is usually NIDDM precipitated early in life by the pregnancy. Both gestational diabetes and NIDDM are characterized by insulin deficiency and by insulin resistance. Long-term follow-up studies have demonstrated that NIDDM or impaired glucose tolerance develop in later life in 50-70% of women with previous gestational diabetes. The adverse effects of pregnancy on the mother with pre-existing diabetes may be minimized by good diabetic control as may be adverse effects on the fetus and neonate of diabetes in the mother. An increased incidence of fetal malformations persists in pregnancies with pre-existing maternal diabetes. Diabetes of any form may be associated with neonatal hypoglycaemia. The aim of therapy is to produce maternal normoglycaemia throughout pregnancy by dietary measures and insulin treatment if required. Women with pre-existing diabetes should tighten their blood glucose control from before conception. Optimization of insulin therapy and diet are required for IDDM and most NIDDM women will require insulin treatment in pregnancy. Gestational diabetics require diet and possibly insulin. Most pregnancies now proceed to term.

Experimental treatment of tendon injury with heparin.

The effect of heparin on the progress of healing in the injured tendon was examined after a standard injury had been created in the Achilles tendons of New Zealand White rabbits. Half of the rabbits were then treated by the intratendinous injection of heparin. The diameters of the injured right hind and the uninjured left hind Achilles tendon and overlying skin were measured using vernier calipers before injury and at one month after injury. At this time histological analysis was carried out on all Achilles tendons and tendon dry weight, collagen concentration and DNA concentration were measured. Orientation of collagen fibres was more pronounced in treated than untreated tendons while cellularity and blood vessel density were less pronounced. Analysis by Students t-test demonstrated a statistically significant difference between treated and untreated tendons in terms of leg diameter (p less than 0.005), dry weight (p less than 0.01) and DNA concentration (p less than 0.01).

Insulin secretion and sensitivity in women fulfilling WHO criteria for gestational diabetes.

Abnormalities of insulin secretion rather than insulin sensitivity are described in women fulfilling the American criteria for gestational diabetes. We examined insulin secretion and insulin sensitivity in 38 women at risk of gestational diabetes categorized according to the less stringent WHO criteria, based on the 75 g oral glucose tolerance test, performed at 24 weeks gestation. Insulin sensitivity was assessed at 28 and 36 weeks using the short insulin tolerance test. Applying WHO criteria, 18 women had GDM. Age and body mass index of the GDM and glucose tolerant women were similar (32.4 +/- 1.1 (SE) vs 32.3 +/- 1.9 yr; 28.7 +/- 1.5 vs 28.8 +/- 1.7 kg m-2, respectively). Fasting glucose was higher in the GDM women than controls (5.1 +/- 0.2 vs 4.5 +/- 0.1 mmol l-1, p < 0.025) while fasting insulin was similar (75 +/- 18 vs 90 +/- 16 pmol l-1). The 30-min insulin concentration during the OGTT was lower in the GDM women than controls (436 +/- 61 vs 788 +/- 152 pmol l-1, p < 0.05), while the insulin sensitivity at 28 (87 +/- 5 vs 76 +/- 5 mumol l-1 min) and 36 weeks (73 +/- 8 vs 76 +/- 8 mumol l-1 min) was similar. A negative correlation existed between the 30-min insulin and 120-min glucose concentration during the OGTT (Rho -0.328, p < 0.05). The WHO criteria for GDM identify women with similar abnormalities of insulin secretion as the more stringent American criteria.

Correcting for ethnicity when defining large for gestational age infants in diabetic pregnancies.

The large-for-gestational-age (LGA) infant, defined as > 90th birthweight percentile, is associated with mild disturbances of maternal glucose tolerance. In the UK the same birthweight percentile charts are used for all ethnic groups when assessing LGA infants. The influence of maternal hyperglycaemia on LGA infants of Asian (Indian Subcontinent) mothers in the UK is likely to be under-reported, as Asian birthweights tend to be lower than White/Europid birthweights. We assessed the number of LGA infants born consecutively to 21 Asian and 26 White/Europid mothers with gestational diabetes mellitus (GDM), delivered between 37 and 42 weeks gestation, and also in 34 Asian and 121 White/Europid mothers with a positive screening test for GDM but a normal 75 g oral glucose tolerance test (OGTT). Large-for-gestational-age infants were identified using both the standard UK percentile charts of the Medical Research Council and percentile charts constructed from 30,418 Asian and 162,477 White/Europid singleton births, delivered between 37 and 42 weeks gestation to non-diabetic mothers delivered in the North West Thames Region of England. The standard Medical Research Council percentile charts, compared with the ethnically derived charts, identified fewer LGA Asian (7/56 vs 15/56) but more White/Europid infants (33/147 vs 21/147). When correcting for ethnicity more Asian than White/Europid GDM mothers delivered LGA infants (9/21 vs 3/26, chi 2 = 4.76, p < 0.05). The maternal 2 h OGTT plasma glucose was a significant independent contributor to birthweight in the Asian (r2 = 0.319, p < 0.0005) but not the White/Europid infants, in whom gestational age and maternal height were significant independent contributors to birthweight (r2 = 0.158, p < 0.0001). We conclude that ethnic influences are important when defining LGA infants and that mild disturbances of maternal glycaemia have a greater influence on the birthweight of Asian than White/Europid infants.

Increased maternal fasting proinsulin as a predictor of insulin requirement in women with gestational diabetes.

Circulating proinsulin was assessed during a 75g OGTT in 55 pregnant women who fulfilled WHO criteria for impaired glucose tolerance before the 32nd gestational week. Proinsulin was assayed retrospectively using a two-site immunoradiometric assay and immunoreactive insulin by radioimmunoassay. Of the 55 women, 19 required insulin treatment in addition to diet later in pregnancy. Fasting proinsulin concentrations were significantly higher in the 19 women who later required insulin treatment compared with the 36 women treated with diet alone (3.4 +/- 0.7 vs 1.8 +/- 0.2 pmol l-1, p < 0.005). There was no difference between the treatment groups of 60 and 120 min proinsulin values during the OGTT. Fasting plasma glucose and immunoreactive insulin were similar in the insulin-treated and diet-treated women and remained similar during the OGTT. No women within the insulin-treated group had a fasting plasma proinsulin value < 1.1 pmol l-1 in contrast with 12 women in the diet-treated group (p = 0.0123). Ten of the 19 insulin-treated women had a fasting plasma proinsulin > 2.5 pmol l-1 compared with 8 of the 36 diet-treated women (p = 0.0346). Fasting proinsulin values early in pregnancy have prognostic implications in women with gestational diabetes.

High prevalence of gestational diabetes in women from ethnic minority groups.

The influence of ethnic origin, body mass index, and parity on the frequency of gestational diabetes was assessed in 11,205 consecutive women attending a multiracial antenatal clinic in London, where all women were screened for gestational diabetes. Logistic regression was used to model the relationship between gestational diabetes and ethnic origin, age, body mass index (BMI), and parity. Results were presented as adjusted odds ratios, where the reference categories are White women, age < 25 years, BMI < 27, and parity < 3. Ethnic origin was the dominant influence on the prevalence of gestational diabetes. Women from ethnic groups other than White had a higher frequency of gestational diabetes than White women (2.9% vs 0.4%, p < 0.001). Compared to White women the relative risk of gestational diabetes in the other ethnic groups was: Black 3.1 (95% confidence limits 1.8-5.5), South East Asian 7.6 (4.1-14.1), Indian 11.3 (6.8-18.8), and miscellaneous 5.9 (3.5-9.9). Increasing age was an independent risk factor. The relative risk was higher in women > or = 35 years in all ethnic groups other than in South East Asian women. Obesity (BMI > or = 27) was a further independent risk factor in all ethnic groups except in the Indian and South East Asian women. Parity > or = 3 increased the relative risk of gestational diabetes in the White, Black, and South East Asian women only.(ABSTRACT TRUNCATED AT 250 WORDS)

Abnormalities of intermediary metabolism following a gestational diabetic pregnancy.

OBJECTIVE: The aim of this study was to compare intermediary metabolism in glucose tolerant women with previous gestational diabetes and control women without a history of gestational diabetes. SUBJECTS: Fifteen women with previous gestational diabetes and 15 controls individually matched for race, age and body mass index were included. Only subjects with normal glucose tolerance were included in this study. METHODS: Plasma glycerol, 3-OH butyrate, non-esterified fatty acids (NEFA), glucose and insulin were measured fasting and following a 75 g oral glucose load. RESULTS: The women with previous gestational diabetes and their matched controls were of similar racial origin, age and body mass index. There was no difference between those with previous gestational diabetes and controls in fasting glycerol, 3-OH butyrate, NEFA, glucose or insulin concentrations. Following the oral glucose load, glycerol, 3-OH butyrate and NEFA concentrations fell in both groups. However, compared with controls at 120 minutes, those with previous gestational diabetes had significantly higher concentrations of glycerol (median 57, range 24-216 vs 27, range 8-89 mumols/l, P less than 0.005) and 3-OH butyrate (9, range 1-18 vs 5, range 2-11 mumols/l, P less than 0.01). NEFA concentrations were similar in the two groups. Despite similar glucose concentrations during the oral glucose tolerance test the insulin response during the first 60 minutes following oral glucose was significantly reduced in the subjects with previous gestational diabetes when compared with controls (insulin area, 0-60 minutes; 2172, range 788-4767 vs 2830, range 996-4784 pmol min/l, P less than 0.05). CONCLUSIONS: Women with a previous history of gestational diabetes, despite having normal glucose tolerance, have defective insulin release with resultant abnormalities of intermediary metabolism.

Ethnic differences in insulin secretion in women at risk of future diabetes.

The plasma glucose and insulin responses to oral glucose were studied in 44 women who had previously had gestational diabetes, but had reverted to normal glucose tolerance. Twenty were White, 14 Black, and 10 Asian. A group of race-, age- and weight-matched controls was also studied. Fasting values of glucose and insulin did not differ significantly between the study group and controls. During the 2 h 75-g OGTT the White and Black previously gestational-diabetic women had similar plasma glucose values to their controls, while the Asian previously gestational-diabetic women had significantly higher glucose values at 30 min (9.2 +/- 0.6 (+/- SE) vs 7.1 +/- 0.3 mmol l-1, p less than 0.02) and at 60 min (8.6 +/- 0.8 vs 6.2 +/- 0.4 mmol l-1, p less than 0.02). Compared with their race-matched controls, the White previously gestational-diabetic women had significantly lower insulin values at 60 min (median 41 range 2-91) vs 56 (15-118) mU l-1, p less than 0.05), and the Black previously gestational-diabetic women had lower values at both 30 min (17 (4-116) vs 53 (22-197) mU l-1) and 60 min (36 (4-148) vs 99 (12-169) mU l-1, p less than 0.05). The insulin values were similar during the OGTT in the Asian previously gestational-diabetic women and their controls.(ABSTRACT TRUNCATED AT 250 WORDS)

A defect in insulin release in women at risk of future non-insulin-dependent diabetes.

1. A study on seven Caucasian glucose-tolerant women with previous gestational diabetes and seven matched control subjects is presented. The insulin response to oral glucose, insulin sensitivity and fasting glucose production rates were measured by using a 75 g oral glucose tolerance test, an insulin tolerance test and a non-radioactive tracer, [6,6-2H]glucose, respectively. 2. Fasting plasma glucose levels were similar between the women with previous gestational diabetes and the control subjects (4.8 +/- 0.3 versus 4.7 +/- 0.2 mmol/l), as were fasting plasma insulin levels (median 4 m-units/l, range 1-13 m-units/l versus median 4 m-units/l, range 1-24 m-units/l). After oral glucose the 60 min plasma glucose levels in the women with previous gestational diabetes were significantly higher (8.5 +/- 0.6 versus 6.7 +/- 0.8 mmol/l, P less than 0.05), whereas the plasma insulin level was significantly lower at both 30 min (median 23 m-units/l, range 4-47 m-units/l versus median 55 m-units/l, range 23-100 m-units/l, P less than 0.02) and at 60 min (median 23 m-units/l, range 4-43 m-units/l versus median 60 m-units/l, range 16-126 m-units/l, P less than 0.02). 3. Insulin sensitivity, expressed as the slope of the regression line of plasma glucose level against time after intravenous infusion of insulin (0.05 unit/kg), was similar in the women with previous gestational diabetes and the control subjects (mean slope, -0.17 +/- 0.01 versus -0.17 +/- 0.01). 4. Fasting glucose production rates were similar in the women with previous gestational diabetes and the control subjects (2.2 +/- 0.3 versus 1.9 +/- 0.1 mg min-1 kg-1).(ABSTRACT TRUNCATED AT 250 WORDS)

Fetal proinsulin and birth weight.

In both diabetic and non-diabetic pregnancies fetal insulin is an important anabolic hormone. Fetal hyperinsulinaemia is associated with accelerated fetal growth and increased birth weight. Insulin and C-peptide concentrations in both umbilical cord and amniotic fluid reflect fetal beta-cell secretion and are correlated with birth weight. In the present study umbilical venous proinsulin and insulin concentrations were measured in 54 term infants born to women with and without mild disturbances of glucose tolerance. Umbilical venous cord proinsulin, assayed using a highly specific immunoradiometric assay, was independently correlated with infant birth weight (Rho = 0.53, p < 0.0001) and birth percentile (Rho = 0.65, p < 0.0001). The correlation between birth weight and birth percentile weight with umbilical venous insulin, measured using a non-specific insulin assay, was lost following correction for the influence of proinsulin. Umbilical venous cord proinsulin appears to be a good indicator of fetal beta-cell activity, and in this study, a superior marker to insulin assayed using a non-specific insulin radioimmunoassay. The longer half-life of proinsulin compared with insulin may contribute to proinsulin being a more robust marker of overall fetal beta-cell activity than insulin.