Managing hyperglycaemia during antenatal steroid administration, labour and birth in pregnant women with diabetes.

Optimal glycaemic control before and during pregnancy improves both maternal and fetal outcomes. This article summarizes the recently published guidelines on the management of glycaemic control in pregnant women with diabetes on obstetric wards and delivery units produced by the Joint British Diabetes Societies for Inpatient Care and available in full at www.diabetes.org.uk/joint-british-diabetes-society and https://abcd.care/joint-british-diabetes-societies-jbds-inpatient-care-group. Hyperglycaemia following steroid administration can be managed by variable rate intravenous insulin infusion (VRIII) or continuous subcutaneous insulin infusion (CSII) in women who are willing and able to safely self-manage insulin dose adjustment. All women with diabetes should have capillary blood glucose (CBG) measured hourly once they are in established labour. Those who are found to be higher than 7 mmol/l on two consecutive occasions should be started on VRIII. If general anaesthesia is used, CBG should be monitored every 30 min in the theatre. Both the VRIII and CSII rate should be reduced by at least 50% once the placenta is delivered. The insulin dose needed after delivery in insulin-treated Type 2 and Type 1 diabetes is usually 25% less than the doses needed at the end of first trimester. Additional snacks may be needed after delivery especially if breastfeeding. Stop all anti-diabetes medications after delivery in gestational diabetes. Continue to monitor CBG before and 1 h after meals for up to 24 h after delivery to pick up any pre-existing diabetes or new-onset diabetes in pregnancy. Women with Type 2 diabetes on oral treatment can continue to take metformin after birth.

Long spin lifetime and large barrier polarisation in single electron transport through a CoFe nanoparticle.

We have investigated single electron spin transport in individual single crystal bcc Co30Fe70 nanoparticles using scanning tunnelling microscopy with a standard tungsten tip. Particles were deposited using a gas-aggregation nanoparticle source and individually addressed as asymmetric double tunnel junctions with both a vacuum and a MgO tunnel barrier. Spectroscopy measurements on the particles show a Coulomb staircase that is correlated with the measured particle size. Field emission tunnelling effects are incorporated into standard single electron theory to model the data. This formalism allows spin-dependent parameters to be determined even though the tip is not spin-polarised. The barrier spin polarisation is very high, in excess of 84%. By variation of the resistance, several orders of magnitude of the system timescale are probed, enabling us to determine the spin relaxation time on the island. It is found to be close to 10 µs, a value much longer than previously reported.

Pathophysiology of postprandial hyperglycaemia in women with type 1 diabetes during pregnancy.

AIMS/HYPOTHESIS: Although maternal hyperglycaemia is associated with increased risk of adverse pregnancy outcome, the mechanisms of postprandial hyperglycaemia during pregnancy are poorly understood. We aimed to describe glucose turnover in pregnant women with type 1 diabetes, according to stage of gestation (early vs late gestation). METHODS: The rates of systemic glucose appearance (R(a)) and glucose disposal (R(d)) were measured in ten pregnant women with type 1 diabetes during early (12-16 weeks) and late (28-32 weeks) gestation. Women ate standardised meals--a starch-rich 80 g carbohydrate dinner and a sugar-rich 60 g carbohydrate breakfast--and fasted between meals and overnight. Stable-label isotope tracers ([6,6-(2)H(2)]glucose and [U-(13)C]glucose) were used to determine R(a), R(d) and glucose bioavailability. Closed-loop insulin delivery maintained stable glycaemic conditions. RESULTS: There were no changes in fasting R(a) (10 ± 2 vs 11 ± 2 µmol kg(-1) min(-1); p = 0.32) or fasting R(d) (11 ± 2 vs 11 ± 1 µmol kg(-1) min(-1); p = 0.77) in early vs late gestation. There was increased hepatic insulin resistance (381 ± 237 vs 540 ± 242 µmol kg(-1) min(-1) × pmol/l; p = 0.04) and decreased peripheral insulin sensitivity (0.09 ± 0.04 vs 0.05 ± 0.02 µmol kg(-1) min(-1) per pmol/l dinner, 0.11 ± 0.05 vs 0.07 ± 0.03 µmol kg(-1) min(-1) per pmol/l breakfast; p = 0.002) in late gestation. It also took longer for insulin levels to reach maximal concentrations (49 [37-55] vs 71 [52-108] min; p = 0.004) with significantly delayed glucose disposal (108 [87-125] vs 135 [110-158] min; p = 0.005) in late gestation. CONCLUSIONS/INTERPRETATION: Postprandial glucose control is impaired by significantly slower glucose disposal in late gestation. Early prandial insulin dosing may help to accelerate glucose disposal and potentially ameliorate postprandial hyperglycaemia in late pregnancy. TRIAL REGISTRATION: ISRCTN 62568875 FUNDING: Diabetes UK Project Grant BDA 07/003551. H.R. Murphy is funded by a National Institute for Health Research (NIHR) research fellowship (PDF/08/01/036). Supported also by the Juvenile Diabetes Research Foundation (JDRF), Abbott Diabetes Care (Freestyle Navigator CGM and sensors free of charge), Medical Research Council Centre for Obesity and Related Metabolic Diseases and NIHR Cambridge Biomedical Research Centre.

Obstetric and perinatal outcomes in pregnancies complicated by Type 1 and Type 2 diabetes: influences of glycaemic control, obesity and social disadvantage.

AIMS: To compare obstetric and perinatal outcomes in women with Type 1 and Type 2 diabetes and relate these to maternal risk factors. METHODS: Prospective cohort study of 682 consecutive diabetic pregnancies in East Anglia during 2006-2009. Relationships between congenital malformation, perinatal mortality and perinatal morbidity (large for gestational age, preterm delivery, neonatal care) with maternal age, parity, ethnicity, glycaemic control, obesity and social disadvantage were examined using bivariable and multivariate models. RESULTS: There were 408 (59.8%) Type 1 and 274 (40.2%) Type 2 diabetes pregnancies. Women with Type 2 diabetes were older (P < 0.001), heavier (P < 0.0001), more frequently multiparous (P < 0.001), more ethnically diverse (p < 0.0001) and more socially disadvantaged (P = 0.0004). Although women with Type 2 diabetes had shorter duration of diabetes (P < 0.0001) and better pre-conception glycaemic control [HbA(1c) 52 mmol/mol (6.9%) Type 2 diabetes vs. 63 mmol/l (7.9%) Type 1 diabetes; p < 0.0001), rates of congenital malformation and perinatal mortality were comparable. Women with Type 2 diabetes had fewer large-for-gestational-age infants (37.6 vs. 52.9%, P < 0.0008), fewer preterm deliveries (17.5 vs. 37.1%, P < 0.0001) and their offspring had fewer neonatal care admissions (29.8 vs. 43.2%, P = 0.001). Third trimester HbA(1c) (OR 1.35, 95% CI 1.09-1.67, P = 0.006) and social disadvantage (OR 0.80, 95% CI 0.67-0.98; P = 0.03) were risk factors for large for gestational age. CONCLUSIONS: Despite increased age, parity, obesity and social disadvantage, women with Type 2 diabetes had better glycaemic control, fewer large-for-gestational-age infants, fewer preterm deliveries and fewer neonatal care admissions. Better tools are needed to improve glycaemic control and reduce the rates of large for gestational age, particularly in Type 1 diabetes.

Cognitive function in 6- to 12-year-old offspring of women with Type 1 diabetes.

AIMS: Maternal diabetes is a recognized risk factor for congenital malformation, perinatal morbidity and obesity in later childhood. The aim of this study is to assess the impact of maternal diabetes on cognitive function in offspring. METHODS: Participants were 6- to 12-year-old offspring of women with Type 1 diabetes. All women received their antenatal care and delivered at one university hospital. HbA(1c) was monitored monthly throughout pregnancy and cognitive function was assessed using the Wechsler Intelligence Scale for Children, version 4. RESULTS: We present results in 40 offspring. There was no difference in overall full-scale IQ compared with UK normative data. However, working memory was poorer than other parts of the Wechsler Intelligence Scale for Children version 4 test and significantly lower compared with UK normative data [8.4 (2.2) vs. 10.1 (3.2), P < 0.01]. We found no correlation between measurement of digit span or HbA(1c) at any stage during pregnancy (r = -0.225 to 0.002), gestational age at delivery (r = -0.178) or infant birthweight ratio (r = -0.176). There was no relationship between working memory score and maternal hypoglycaemia episodes or maternal duration of diabetes. Comparing infants born before (n = 9) or after 37 weeks' gestation, digit span was non-significantly lower [7.9 (1.8) vs. 8.6 (2.4)]. DISCUSSION: These results suggest offspring of women with Type 1 diabetes have normal overall cognitive function but poorer working memory. We have been unable to identify specific risk factors. Further larger studies are required to increase the understanding of this memory defect and identify any modifiable risk factors.

Cord blood telomere length, telomerase activity and inflammatory markers in pregnancies in women with diabetes or gestational diabetes.

AIMS: We tested the hypothesis that diabetes during pregnancy leads to chromosomal DNA damage and telomere attrition in the feto placental unit and cord blood, and provides evidence for intrauterine programming towards a senescent phenotype in the offspring. METHODS: We obtained cord blood from pregnant women with pregestational Type 1 diabetes (n=26), Type 2 diabetes (n=20) or gestational diabetes (n=71), and control subjects without diabetes (n=45, n=76 and n=81, respectively) matched for maternal and gestational age. We measured cord blood mononuclear cell telomere length, telomerase activity (a reverse transcriptase that limits telomere attrition), and concentrations of insulin, high-sensitivity C-reactive protein (hs-CRP) and soluble intercellular adhesion molecule-1 (sICAM-1). RESULTS: We found no significant differences between groups in cord blood telomere length in any nucleated cell type, or in hs-CRP or sICAM-1 concentrations, but telomerase activity was higher in cord blood from Type 1 (P<0.05) and gestational diabetes pregnancies (P<0.05), but not in Type 2 diabetes pregnancies. There were no significant relationships between glycaemic control, cord blood telomere length, telomerase activity or inflammatory markers in any group. CONCLUSIONS: We found no difference in cord blood telomere length in pregnancies of women with diabetes compared with control subjects, but higher cord blood telomerase activity in Type 1 and gestational diabetes. This may reflect upregulated telomere reverse transcriptase in response to in utero oxidative DNA and telomere damage. These observations are relevant to the hypothesis that diabetes during pregnancy leads to in utero preprogramming towards senescence in the offspring.

Personal experiences of women with diabetes who do not attend pre-pregnancy care.

AIMS: To explore the views of women who did not attend pre-pregnancy care (PPC), in particular their accounts of contraception, previous pregnancies and the influence of healthcare advice. METHODS: We conducted semi-structured interviews with 29 pregnant women (21 with Type 1 diabetes, eight with Type 2 diabetes) at three UK specialist diabetes antenatal clinics. Interviews explored women's journeys to becoming pregnant, including use of contraception, their views regarding diabetes and pregnancy and the factors which encouraged and discouraged them from attending PPC. RESULTS: All women had some understanding of the issues concerning diabetes during pregnancy, predominantly regarding the benefits of PPC (90%) and optimal glycaemic control (80%) and risks of malformation (48%) and macrosomia (35%). Most were not regularly using contraception (70%), having stopped deliberately (45%), become unintentionally less rigorous (28%) or experienced side effects/contraindications (14%). Knowledge concerning the risks of pregnancy (90%) and past pre-conception counselling (38%) did not encourage women to attend PPC, and neither did personal experience of miscarriage, malformation or stillbirth in women with previous poor pregnancy outcome (41%). Barriers included conceiving faster than anticipated (45%), fertility concerns (31%), negative experiences with health professionals (21%), desire for a 'normal' pregnancy (17%) and the logistics of attending (10%). CONCLUSIONS: More integrated diabetes and reproductive health/contraceptive advice, increased awareness of the potentially short time between stopping contraception and conception and more intensive support between pregnancies are required, particularly for women with previously poor outcomes. Research is also needed into how communication between health professionals and women with diabetes can be improved.

Absence of telomere shortening and oxidative DNA damage in the young adult offspring of women with pre-gestational type 1 diabetes.

AIMS/HYPOTHESIS: The offspring of mothers with pre-gestational type 1 diabetes (PGDM) may be at increased risk of glucose intolerance and cardiovascular disease in childhood. The underlying causes of these observations, and whether they persist into adulthood, are unknown. The aim of the present study was to test the hypothesis that fetal chromosomal telomere oxidative DNA damage resulting from maternal PGDM programmes the offspring towards a senescent phenotype that is detectable in young adulthood. METHODS: We studied 21 young adult offspring (age 16-23 years) with a maternal history of PGDM and 23 age- and weight-matched controls with no maternal history of diabetes. All participants underwent anthropometric assessments, a standard 75 g OGTT, measurement of peripheral blood mononuclear cell and skin fibroblast telomere length, fibroblast senescence, cell DNA damage (by determination of 8-oxoguanine levels using flow cytometry), plasma lipoprotein profiles (determined by nuclear magnetic resonance) and plasma levels of soluble adhesion molecules and inflammatory markers. RESULTS: The groups did not differ significantly with respect to anthropometric measures, glucose tolerance, fasting and 2 h plasma insulin levels during OGTT, estimated peripheral insulin resistance, peripheral blood mononuclear cell or fibroblast telomere length, DNA damage or senescence in vitro, plasma NMR lipoprotein profiles or levels of high-sensitivity C-reactive protein. Plasma concentrations of soluble intercellular adhesion molecule 1 (sICAM-1; p < 0.05) and IL-6 (p = 0.08) were higher in the PGDM offspring. CONCLUSIONS/INTERPRETATION: Young adult offspring of mothers with PGDM do not differ in terms of glucose tolerance, DNA damage or telomere length from controls of the same weight and BMI. This does not preclude such abnormalities at an earlier age, but there is no evidence of telomere damage as a pre-programming mechanism in the young adults enrolled in this study.

Acute unilateral cataract in a postpartum adolescent with poorly-controlled type 1 diabetes.

Acute cataract is recognized as a rare complication in adolescents with type 1 diabetes mellitus and may be associated with rapid improvement in glycaemia in patients with newly diagnosed diabetes. Transient cataracts, which resolve following improved metabolic control, and irreversible cataracts requiring surgery have also previously been documented. Development or progression of retinopathy may complicate pregnancy in women with diabetes. To our knowledge, we present the first case report of an acute cataract developing postpartum in a woman with type 1 diabetes. This rare case serves to demonstrate a possible association between acute cataract and altered glycaemic control in pregnancy. Acute cataract should be considered in any woman with diabetes who develops sudden visual loss following pregnancy.

Glycaemic control throughout pregnancy and risk of pre-eclampsia in women with type I diabetes.

The aim of this study was to examine the influence of pre-pregnancy care and its effect on early glycaemic control and also the effect of glycaemic control in later pregnancy on risk of pre-eclampsia in women with type I diabetes. A prospective cohort study of 290 consecutive nonselected pregnancies in women with type I diabetes was performed from 1991 to 2002. We examined the relationship of monthly glycosylated haemoglobin (HbA1c) level, pre-pregnancy care, parity, diabetes duration, microvascular complications, maternal age, weight and smoking with risk of pre-eclampsia. Pre-eclampsia developed in 31/243 singleton births (12.8%). HbA1c level at 24 weeks was significantly increased in women with pre-eclampsia compared with women without pre-eclampsia (6.0 versus 5.6%, P= 0.017) and was, after nulliparity, the strongest independent predictor of increased risk (OR 1.65 for each 1% increase in HbA1c; P= 0.01). In contrast, there was no relationship between pre-pregnancy care or HbA1c level at booking and risk of pre-eclampsia.

Trends in bed occupancy for inpatients with diabetes before and after the introduction of a diabetes inpatient specialist nurse service.

AIMS: To compare diabetes bed occupancy and inpatient length of stay, before and after the introduction of a dedicated diabetes inpatient specialist nurse (DISN) service in a large UK Hospital. METHODS: We analysed bed occupancy data for medical or surgical inpatients for 6 years (1998-2004 inclusive), with a DISN service in the final 2 years. Excess bed days per diabetes patient were derived from age band, specialty, and seasonally matched data for all inpatients without diabetes. We also analysed the number of inpatients with known diabetes who did not have diabetes recorded as a discharge diagnosis. RESULTS: There were 14,722 patients with diabetes (9.7% of all inpatients) who accounted for 101 564 occupied bed days (12.4% of total). Of these, 18 161 days (17.8%) were excess compared with matched patients without diabetes, and were concentrated in those < 75 years old. Mean excess bed days per diabetes inpatient under 60 years of age was estimated to be 1.9 days before the DISN appointment, and this was reduced to 1.2 bed days after the appointment (P = 0.03). This is equivalent to 700 bed days saved per year per 1000 inpatients with diabetes under 60 years old, with an identical saving for those aged 61-75 years (P = 0.008), a saving of 1330 diabetes bed days per year by one DISN. Excess diabetes bed occupancy was 167 excess bed days per year per 1000 patients with diabetes in the local population after the DISN appointment. One quarter of the known Type 2 diabetes population were admitted annually, but one quarter of patients had no diagnostic code for diabetes. CONCLUSIONS: Diabetes excess bed occupancy was concentrated in patients < 75 years old, and this was reduced notably following the introduction of a DISN service.

A mobile screening programme for the cardiovascular and microvascular complications of Type 2 diabetes in primary care.

The Diabetes National Service framework (NSF), and the quality payments in the new contract for UK General Practitioners, promote regular screening for diabetes complications. The new contract also includes immediate incentives to meet screening and quality targets, but it will be difficult to meet these targets in primary care. We have developed a mobile 'annual review' programme for patients with Type 2 diabetes managed solely in primary care, that screens for cardiovascular disease, hypertension, retinopathy and neuropathy at the patient's general practice, and gives written foot care, dietary advice and level 1 smoking cessation advice to all patients.

The pregnancies of women with Type 2 diabetes: poor outcomes but opportunities for improvement.

AIM: To compare the outcomes of Type 1 and Type 2 diabetic pregnancies and identify risk factors for poor outcome of Type 2 pregnancies METHODS: The data from all (389 Type 1 and 146 Type 2) pre-gestational diabetic pregnancies from 10 UK hospitals were collected prospectively. RESULTS: The Type 2 mothers were less likely to have documented pre-pregnancy counselling (28.7 vs. 40.5%; P<0.05) or be taking folic acid at conception (21.9 vs. 36.4%; P<0.001) than Type 1 mothers. The percentage of pregnancies having a serious adverse outcome was higher in Type 2 patients (16.4 vs. 6.4%; P=0.002). Congenital abnormalities (12.3% in Type 2 vs. 4.4% in Type 1; P=0.002) accounted for most of this difference. The HbA1c of the Type 2 patients was similar to that of the Type 1 with mean first trimester HbA1c of 7.22 and 7.35%, respectively (P=0.5). Treatment with oral hypoglycaemic agents [odds ratio (OR), 1.8; 95% confidence interval (CI), 1.0-3.3; P=0.04], body mass index (OR, 1.09; 95% CI, 1.01-1.18; P=0.02) and folic acid supplementation (OR, 0.3; 95% CI, 0.09-1.0; P=0.04) were all independently associated with congenital malformation. CONCLUSION: Type 2 diabetic pregnancies are characterized by poor pre-pregnancy planning, inadequate folic acid supplementation and treatment with oral hypoglycaemic agents, all of which may contribute to the serious adverse outcomes affecting one in six Type 2 diabetic pregnancies. These remediable aspects of the pre-pregnancy care of women with Type 2 diabetes provide opportunities for improving the outcome towards that of women with Type 1 diabetes.

An integrated mobile foot and retinal screening programme for people with Type 2 diabetes managed in primary care.

AIMS: To undertake a vascular and neurological assessment on the feet of all patients with Type 2 diabetes managed solely in local primary care. METHODS: A mobile screening podiatrist (working with an existing mobile retinal screening programme) screened a selected population of 4022 patients with Type 2 diabetes managed solely in 82 general practices. Doppler pressure assessments of peripheral vasculature, bioesthesiometer and monofilament assessment of peripheral neuropathy. RESULTS: This service was administratively simple to set up and integrated well with the retinal screening service and secondary care foot clinic, and was valued by the practices. Disease prevalences were 1.04% for foot ulceration, 19% for peripheral vascular disease and up to 29% for peripheral neuropathy. CONCLUSIONS: This programme screens all patients with known diabetes managed solely in primary care within a district and describes foot morbidity and allows risk stratification. This pattern of service could be a useful template for discussing the diabetes National Service Framework with primary care groups.

Impact of pregnancy on the progression of diabetic retinopathy in Type 1 diabetes.

AIMS: To evaluate the impact of pregnancy on the progression of diabetic retinopathy in women with Type 1 diabetes mellitus and to identify risk factors for the progression of retinopathy during pregnancy. METHODS: One hundred and seventy-nine pregnancies in 139 women with pregestational Type 1 diabetes were studied prospectively between January 1990 and December 1998. Dilated fundal examination was performed at booking, 24 weeks and 34 weeks or 4-6 weekly if retinopathy present at booking. Data were collected on glycaemic control (HbA(1c)) throughout pregnancy. RESULTS: Progression to proliferative retinopathy was seen in four (2.2%) pregnancies while moderate progression was seen in a further five (2.8%) pregnancies. Progression of retinopathy was significantly increased in women with duration of diabetes 10-19 years compared with duration < 10 years (10% vs. 0%; P = 0.007) and in women with moderate to severe background retinopathy at booking (30% vs. 3.7%; P = 0.01). Although HbA(1c) at booking was higher (7.5% vs. 6.6%; P = 0.08) and the fall in HbA(1c) between booking and 24 weeks was greater (1.6% vs. 1.2%; P = 0.2) in those women showing progression of retinopathy, these changes were not significant. CONCLUSIONS: Progression of retinopathy in pregnancy was uncommon (5.0% pregnancies) but was significantly more common in women with duration of diabetes > 10 years and in women with moderate to severe retinopathy at baseline. Laser therapy was needed in 2.2% pregnancies, which is much lower than that reported in earlier studies. Diabet. Med. 18, 573-577 (2001)

Prevalence of HFE (hemochromatosis gene) mutations in unselected male patients with type 2 diabetes.

To assess the prevalence of mutations in the HFE (hemochromatosis) gene in unselected male patients with type 2 diabetes, we examined 220 white men without known diabetes and 220 age-matched white men with type 2 diabetes for mutations in the HFE gene. Nucleotide 845 (C282Y) and 187(H63D) alleles were amplified by polymerase chain reaction (PCR) with lymphocyte DNA. The PCR products were analyzed by restriction enzyme digestion. One of the 220 patients (0.45%) with diabetes was homozygous for the HFE 845A (C282Y) mutation and 25 (11.3%) were heterozygous for the same mutation, of whom 3 (1.3%) were compound heterozygotes also carrying the HFE 187G (H63D) mutation. These frequencies did not differ significantly from the control population without diabetes. There is no evidence that HFE mutations are found in excess in unselected male patients with type 2 diabetes, and there is no indication for a population-based search for an excess of these alleles in type 2 diabetes.

The relationships of concentrations of insulin, intact proinsulin and 32-33 split proinsulin with cardiovascular risk factors in type 2 (non-insulin-dependent) diabetic subjects.

Standard radioimmunoassay for insulin may substantially overestimate levels of insulin because of cross-reaction with other insulin-like molecules. We have measured concentrations of insulin, intact proinsulin and 32-33 split proinsulin using two-site monoclonal antibody based immunoradiometric assays, and of insulin by a standard radioimmunoassay ("immunoreactive insulin") in 51 Type 2 (non-insulin-dependent) diabetic subjects in the fasting state. The relationships of these concentrations were sought with those of total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol, triglyceride, plasminogen activator inhibitor, blood pressure, and indices of body fat distribution. Significant relationships were apparent between concentrations of "immunoreactive insulin" as measured by standard radioimmunoassay and triglyceride (rs = 0.42, p less than 0.001), total cholesterol (rs = 0.25, p = 0.038), high density lipoprotein cholesterol (rs = -0.30, p = 0.018) and body mass index (rs = 0.30, p = 0.017), but only the relationships with triglyceride (rs = 0.36, p = 0.006) and body mass index (rs = 0.26, p = 0.34) remained significant when concentrations of immunoradiometrically measured insulin were employed. Concentrations of 32-33 split proinsulin, which comprises the major insulin-like molecule in these subjects, correlated positively with triglyceride (rs = 0.33, p = 0.009), total cholesterol (rs = 0.23, p = 0.050), and plasminogen activator inhibitor (rs = 0.26, p = 0.049), and negatively with high density lipoprotein cholesterol (rs = -0.29, p = 0.021).(ABSTRACT TRUNCATED AT 250 WORDS)

Radioimmunoassay may overestimate insulin in non-insulin-dependent diabetics.

We have compared insulin concentrations measured by radioimmunoassay (RIA) in plasma from 50 fasting non-insulin-dependent diabetics (NIDDM) with those measured by a new monoclonal antibody-based two-site immunoradiometric assay (IRMA) of insulin (which has no significant cross-reaction with proinsulin-like molecules). We find that the RIA measures the sum of the insulin and proinsulin like molecules and that the IRMA insulin concentrations are 38% of those measured by the RIA in those diabetic subjects. We conclude that the importance of insulin deficiency in NIDDM may have been obscured by this error.

The effect of thyroid disease on proinsulin and C-peptide levels.

C-peptide and proinsulin levels were studied in hyper and hypothyroidism both pre and post-treatment and in comparison to matched normals. Fasting C-peptide was reduced in untreated hyperthyroidism (0.4 +/- 0.2 (mean +/- SEM) vs 0.7 +/- 0.2 nmol/l, P less than 0.05) but returned to normal levels following treatment. Fasting proinsulin was elevated in untreated hyperthyroidism (3.6 +/- 0.7 vs 2.4 +/- 0.5 pmol/l, P less than 0.05) also returning to normal after treatment. A similar pattern was seen after oral glucose. The increased proinsulin and reduced C-peptide suggest there may be a defect of proinsulin processing in hyperthyroidism. Fasting C-peptide was reduced in untreated hypothyroidism (0.4 +/- 0.1 vs 0.7 +/- 0.1 nmol/l, P less than 0.05) and also returned to normal after treatment. Fasting proinsulin did not differ significantly from controls. However, proinsulin was reduced after oral glucose (4.7 +/- 0.7 vs. 7.9 +/- 2.0 pmol/l, P less than 0.05) as was C-peptide (0.9 +/- 0.2 vs 2.6 +/- 0.3 nmol/l, P less than 0.05). Both returned to normal after treatment. These findings suggest there are abnormalities of proinsulin and C-peptide levels in both hyper and hypothyroidism.

Estimates of normal binding of a human recombinant alpha interferon to peripheral blood mononuclear cells from a study matching healthy subjects to subjects with insulin dependent diabetes.

This study compares the binding of a human recombinant alpha-interferon to peripheral blood mononuclear cells (PBMC) from patients with insulin dependent diabetes (IDDM) mellitus and control subjects. Diurnal and longer term of variation, feeding, fasting and haemoglobin glycosylation were examinated for their influence on interferon binding to PBMC. No gross differences in binding were demonstrated, in particular no effect of glucose levels was seen on the binding of interferon alpha-2 to PBMC.