David R. Hadden

Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study

Abstract Objective: To determine the relation between exposure to glycaemia over time and the risk of macrovascular or microvascular complications in patients with type 2 diabetes. Design: Prospective observational study. Setting: 23 hospital based clinics in England, Scotland, and Northern Ireland. Participants: 4585 white, Asian Indian, and Afro-Caribbean UKPDS patients, whether randomised or not to treatment, were included in analyses of incidence; of these, 3642 were included in analyses of relative risk. Outcome measures: Primary predefined aggregate clinical outcomes: any end point or deaths related to diabetes and all cause mortality. Secondary aggregate outcomes: myocardial infarction, stroke, amputation (including death from peripheral vascular disease), and microvascular disease (predominantly retinal photo-coagulation). Single end points: non-fatal heart failure and cataract extraction. Risk reduction associated with a 1% reduction in updated mean HbA1c adjusted for possible confounders at diagnosis of diabetes. Results: The incidence of clinical complications was significantly associated with glycaemia. Each 1% reduction in updated mean HbA1c was associated with reductions in risk of 21% for any end point related to diabetes (95% confidence interval 17% to 24%, P<0.0001), 21% for deaths related to diabetes (15% to 27%, P<0.0001), 14% for myocardial infarction (8% to 21%, P<0.0001), and 37% for microvascular complications (33% to 41%, P<0.0001). No threshold of risk was observed for any end point. Conclusions: In patients with type 2 diabetes the risk of diabetic complications was strongly associated with previous hyperglycaemia. Any reduction in HbA1c is likely to reduce the risk of complications, with the lowest risk being in those with HbA1c values in the normal range (<6.0%).

Beta‐cell deterioration determines the onset and rate of progression of secondary dietary failure in Type 2 diabetes mellitus: the 10‐year follow‐up of the Belfast Diet Study

Secondary failure of plasma glucose control following initial successful response to diet therapy may be due to dietary indiscretion, or to progression of the intrinsic diabetic condition. We report a 10‐year prospective natural history study of 432 newly diagnosed diabetic patients aged 40–69 years undertaken to assess the effect of intensive dietary management, where patients were transferred to insulin, or oral hypoglycaemic therapy (tolbutamide, metformin) by predetermined criteria of weight and plasma glucose. Secondary failure to diet therapy occurred in 41 patients in years 2–4, 67 patients in years 5–7, and 51 patients in years 8–10; 173 patients remained on diet alone until death or the end of the study. Continuation on diet alone was associated with a lower ongoing fasting plasma glucose, greater beta‐cell function assessed by an oral glucose tolerance test at 6 months, and increasing age. The rate of rise of fasting plasma glucose was inversely related to the duration of successful dietary therapy, but mean weight remained constant in all groups while on diet alone. The ongoing fall in beta‐cell function assessed by HOMA modelling closely mirrored the progressive rise in fasting plasma glucose: there was no change in mean insulin sensitivity in any of the groups.

Neuroendocrine tumors: A European view

A center in Belfast, Northern Ireland, has established a register for tumors of the gastroenteropancreatic endocrine system. Carcinoid tumors occur most frequently. Of the non-carcinoid tumors, insulinomas, gastrinomas, and unknown types have the highest incidence, with other types being extremely rare. The potentially remediable nature of the tumors is stressed, and frequently a good quality of life can be experienced even in the presence of metastatic disease. The syndromes are probably underdiagnosed as they present with clinical features for which there are more common explanations, and appropriate diagnostic methods are therefore not used. The management of the syndromes is reviewed with particular emphasis on the treatment of patients with inoperable disease. Histamine (H2)-receptor antagonist therapy has made an impact in Zollinger-Ellison syndrome, and streptozotocin and somatostatin analogues can control tumor growth and endocrine syndromes, respectively.

Normal and abnormal maternal metabolism during pregnancy

Metabolic adaptations during pregnancy are essential to meet the physiological demands of pregnancy as well as adequate growth and development of the fetus. There has been considerable interest in carbohydrate metabolism during pregnancy, with diabetes, the main disorder of glucose metabolism, a considerable focus for research. Whereas disorders of protein and lipid metabolism are recognised during pregnancy, their influence has received less attention. Fasting glucose values fall in early pregnancy with a rise in plasma free fatty acids, enhanced ketogenesis and a fall in plasma amino acids. Decreased hepatic insulin sensitivity in later pregnancy plays a key role in bringing about the appropriate changes in carbohydrate, lipid and amino acid metabolism which are essential for normal fetal development and survival.

Maternal Glucose at 28 Weeks of Gestation Is Not Associated With Obesity in 2-Year-Old Offspring: The Belfast Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Family Study

OBJECTIVE Diabetes during pregnancy is a strong risk factor for obesity in the offspring, but the age at which this association becomes apparent is unknown. The purpose of this study was to examine the relation of glycemia during pregnancy with anthropometry in offspring of nondiabetic pregnant women from the Belfast U.K. center of the multinational Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study. RESEARCH DESIGN AND METHODS Women from the HAPO Study were invited to participate in follow-up of their offspring aged 2 years. Measurements included height, weight, and thickness of triceps, subscapular, and suprailiac skinfolds. RESULTS A total of 1,165 offspring (73% of eligible children; 598 boys and 567 girls) were seen from ages 22–30 completed months. The only association that reached statistical significance was between categories of maternal 1-h glucose and BMI Z score ≥85th percentile at 2 years (P = 0.017). Overall the correlations between maternal glucose during pregnancy and BMI Z score at age 2 years were weak (fasting glucose r = 0.05, P = 0.08; 1-h glucose r = 0.04, P = 0.22; 2-h glucose r = 0.03, P = 0.36; and area under the curve for glucose r = 0.04, P = 0.18). CONCLUSIONS This study found little association between maternal glucose during pregnancy and obesity in the offspring at this young age. These findings are not unexpected given that study results for young offspring whose mothers had diabetes during pregnancy were indistinguishable from those for normal offspring at this age. It will be interesting to see whether, as these children age, maternal glucose during pregnancy in the ranges included in the HAPO Study will be associated with obesity in their children.

Preprandial versus postprandial blood glucose monitoring in type 1 diabetic pregnancy: A randomized controlled clinical trial ☆

OBJECTIVEnThis study was undertaken to compare preprandial and postprandial capillary glucose monitoring in pregnant women with type 1 diabetes.nnnSTUDY DESIGNnSixty-one women with type 1 diabetes were randomly assigned at 16 weeks gestation to preprandial or postprandial blood glucose monitoring using memory-based glucose reflectance meters throughout pregnancy. Serial measurements of hemoglobin A1c and fructosamine were obtained throughout pregnancy. Insulin, glucose, and insulin-like growth factor-I (IGF-I) were measured in cord blood at delivery. Neonatal anthropometric measures were performed within 72 hours of deliverynnnRESULTSnMaternal age, parity, age of onset of diabetes, number of prior miscarriages, smoking status, social class, weight gain in pregnancy, and compliance with therapy were similar in the two groups. The postprandial monitoring group had a significantly reduced incidence of preeclampsia (3% vs 21%, P<.048), a greater success in achieving glycemic control targets (55% vs 30%, P<.001) and a smaller neonatal triceps skinfold thickness (4.5+/-0.9 vs 5.1+/-1.3, P=.05).nnnCONCLUSIONnPostprandial capillary blood glucose monitoring in type 1 diabetic pregnancy may significantly reduce the incidence of preeclampsia and neonatal triceps skinfold thickness compared with preprandial monitoring.

LONG-TERM GLYCAEMIC CONTROL AND DIABETIC RETINOPATHY

216 patients with insulin-dependent diabetes mellitus were studied by retinal photography, and the absence or presence of retinopathy was related to the mean of serial glycosylated haemoglobin measurements (mean HbA1) carried out every 3 months during the previous 6 years. 122 patients had no diabetic retinopathy, 86 had background retinopathy, and 8 proliferative retinopathy. Mean HbA1 levels showed a strong correlation with increasingly severe grades of retinopathy, even when differences in duration of diabetes were taken into account. Proliferative retinopathy was seen only in patients with mean HbA1 above 10%. These results support the view that the development of diabetic retinopathy is related to long-term glycaemic control and emphasise the desirability, and possible benefit, of achieving control as close to normal as is possible for each individual patient.

Diabetic retinopathy in pregnancy

Summary. The records of 23 insulin‐dependent diabetics who had serial ophthalmological examinations during pregnancy and afterwards were reviewed. Fourteen pregnancies occurred in 10 patients with no retinopathy; 30% of these patients had obstetric complications. The mean birthweight was 3.5 kg. Ophthalmological status was unchanged in this group. In eight patients with background retinopathy during 10 pregnancies the obstetric complication rate was 70% and mean birth‐weight 3.3 kg. During pregnancy there was no evidence of progression of retinopathy. One patient developed proliferative retinopathy 4 years later. Five patients had proliferative retinopathy. The mean age (32 years) and duration of diabetes at index pregnancy (18 years) was greater than for the other groups. All patients developed pre‐eclampsia and mean birthweight was 2.8 kg. Four of these patients required argon laser photocoagulation in association with pregnancy for progressive retinopathy; one died subsequently from end‐stage diabetic nephropathy; the other four have maintained their pre‐pregnancy visual acuity from 4 to 10 years.

Insulin sensitivity in pre‐eclampsia

Objective To investigate whether pre‐eclampsia is associated with an exaggeration of the insulin resistance seen in normotensive pregnancy.

Obstetric and diabetic care for pregnancy in diabetic women: 10 years outcome analysis, 1985–1995

Aimu2003 Ten‐year outcome analysis of all pregnancies in diabetic women in a population of 1.5 million people.