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SummaryAims Gestational diabetes mellitus (GDM) is associated with adverse maternal and fetal outcome. Screening for GDM is therefore recommended but the best screening method remains controversial. This prospective, randomized study compared a risk factor-based screening programme with a universally based one. Methods Subjects were randomized at booking to one of two groups: the risk factor group had a 3-h 100-g oral glucose tolerance test (OGTT) at 32 weeks if any risk factor for GDM was present; the universal group had a 50-g glucose challenge test performed and if their plasma glucose at 1 h was ≥ 7.8 mmol/l, a formal 3-h 100-g OGTT was then performed. Results Universal screening detected a prevalence of GDM of 2.7%, significantly more than the 1.45% detected in the risk factor screened group (P < 0.03). Universal screening facilitated earlier diagnosis than risk factor screening – mean gestation 30 ± 2.6 weeks vs. 33 ± 3.7 weeks (P < 0.05). A higher rate of spontaneous vaginal delivery at term, and lower rates of macrosomia, Caesarean section, prematurity, pre-eclampsia and admission to neonatal intensive care unit were observed in the universally screened, early diagnosis group. Conclusions Universal screening for GDM is superior to risk factor based screening – detecting more cases, facilitating early diagnosis and is associated with improved pregnancy outcome. [ABSTRACT FROM AUTHOR]

SummaryIntroduction Patients with Type 1 diabetes mellitus have a high prevalence of coeliac disease, symptoms of which are often mild, atypical, or absent. Untreated coeliac disease is associated with an increased risk of malignancy, particularly of lymphoma. We describe four patients with Type 1 diabetes mellitus and coeliac disease who developed lymphoma. Case reports Two patients were male and two female. In three patients, coeliac disease and lymphoma were diagnosed simultaneously. Enteropathy-associated T cell lymphoma occurred in two patients, Hodgkin’s disease in one, and B cell lymphoma in one. Response to treatment was in general poor, and three patients died soon after the diagnosis of lymphoma was made. Conclusion As the relative risk of lymphoma is reduced by a gluten-free diet, a high index of suspicion for coeliac disease should exist in all Type 1 diabetic patients with unexplained constitutional or gastro- intestinal symptoms. Keywords coeliac disease, lymphoma, Type 1 diabetes mellitus. [ABSTRACT FROM AUTHOR]

Introduction: Patients with Type 1 diabetes mellitus have a high prevalence of coeliac disease, symptoms of which are often mild, atypical, or absent. Untreated coeliac disease is associated with an increased risk of malignancy, particularly of lymphoma. We describe four patients with Type 1 diabetes mellitus and coeliac disease who developed lymphoma., Case Reports: Two patients were male and two female. In three patients, coeliac disease and lymphoma were diagnosed simultaneously. Enteropathy-associated T cell lymphoma occurred in two patients, Hodgkin's disease in one, and B cell lymphoma in one. Response to treatment was in general poor, and three patients died soon after the diagnosis of lymphoma was made., Conclusion: As the relative risk of lymphoma is reduced by a gluten-free diet, a high index of suspicion for coeliac disease should exist in all Type 1 diabetic patients with unexplained constitutional or gastrointestinal symptoms.

Patients with Type 1 diabetes mellitus have an increased risk of ischaemic heart disease (IHD). When diabetes is complicated by nephropathy this risk is further increased and asymptomatic IHD is common. New techniques for non-invasive cardiac evaluation are now available and one of these, Dobutamine Stress Echocardiography (DSE), was studied in subjects with Type 1 DM and nephropathy who had no evidence of IHD. DSE was performed on 18 subjects (13 male, 5 female; mean age 37.8 +/- 3.4 years), diabetes duration 23.7 +/- 1.2 years and nephropathy diagnosed for 10.9 +/- 1.3 years. There were 7 (38%) positive scans-suggesting asymptomatic IHD; 16.7% of subjects studied had a significant arrhythmia. Coronary angiography was performed in 6 of the 7 subjects with positive DSEs and was positive in only 2. These results suggest that DSE has a high rate of false positive results in Type 1 DM patients suffering from nephropathy and may limit its usefulness in these subjects.

We describe four cases of the Wolfram syndrome; a rare congenital syndrome characterised in it's complete form by diabetes mellitus, diabetes insipidus, optic atrophy, nerve deafness and dilatation of the urinary tract. All four of the cases described developed grand mal epilepsy in their second and third decades. Two of the cases developed progressive ataxia. There was one death due to status epilepticus. Absence of most of the corpus callosum and of the septum pellucidum was noted at autopsy. This pathological finding has not been reported previously in this syndrome. These cases highlight the neuro-degenerative aspects of the Wolfram syndrome. The literature on neurological aspects of the syndrome is reviewed.

Non-insulin-dependent diabetes mellitus patients are those patients who do not require insulin for survival and do not have gestational, secondary, or malnutrition-related diabetes. They may require insulin to maintain good health. Therapy in NIDDM should attempt to reverse the coexisting defects of insulin deficiency and insulin resistance that lead to hepatic glucose over-production and diminished glucose tissue utilization. Both sulfonylureas and insulin can achieve near normal FPGs and HbA1c concentrations in mild to moderately severe NIDDM. Both can reduce insulin resistance and both increase insulin availability. Evidence exists, however, showing that prevention of post-prandial hyperglycemia, whose significance is unknown, may require soluble preprandial insulin. Treatment goals should be realistic and discussed with the patient. In younger patients, the aim should be to achieve normoglycemia, while in those who have other significant medical or social problems, or who are of advanced age, diabetic control may, out of necessity, need to be relaxed. At presentation a diet and exercise program should be initiated and the patient observed if clinically well. If diet fails to reduce the FPG below 108 mg/dl, additional therapy should be used. In mild to moderate NIDDM, sulfonylurea or basal insulin (given as once daily long- or intermediate-acting insulin) can be equally successful without the need for rigid dietary habits. More severe degrees of NIDDM or patients with sulfonylurea failure not caused by dietary indiscretion will require more complex insulin regimens. The socially dependent patient requiring insulin should have as simple a regimen as possible. The insulin-resistant patient undergoing surgery or with an intercurrent illness is most easily managed with a variable rate insulin infusion that allows prediction of subsequent subcutaneous insulin requirements. Combination insulin-sulfonylurea therapy should be reserved for patients failing to achieve acceptable glycemic control when insulin and sulphonylurea are used separately. It may improve control or lessen insulin requirements.

Patients with noninsulin-dependent diabetes mellitus (NIDDM) have both preprandial and postprandial hyperglycemia. To determine the mechanism responsible for the postprandial hyperglycemia, insulin secretion, insulin action, and the pattern of carbohydrate metabolism after glucose ingestion were assessed in patients with NIDDM and in matched nondiabetic subjects using the dual isotope and forearm catheterization techniques. Prior to meal ingestion, hepatic glucose release was increased (P less than 0.001) in the diabetic patients measured using [2-3H] or [3-3H] glucose. After meal ingestion, patients with NIDDM had excessive rates of systemic glucose entry (1,316 +/- 56 vs. 1,018 +/- 65 mg/kg X 7 h, P less than 0.01), primarily owing to a failure to suppress adequately endogenous glucose release (680 +/- 50 vs. 470 +/- 32 mg/kg X 7 h, P less than 0.01) from its high preprandial level. Despite impaired suppression of endogenous glucose production during a hyperinsulinemic glucose clamp (P less than 0.001) and decreased postprandial C-peptide response (P less than 0.05) in NIDDM, percent suppression of hepatic glucose release after oral glucose was comparable in the diabetic and nondiabetic subjects (45 +/- 3 vs. 39 +/- 2%). Although new glucose formation from meal-derived three-carbon precursors (53 +/- 3 vs. 40 +/- 7 mg/kg X 7 h, P less than 0.05) was greater in the diabetic patients, it accounted for only a minor part of this excessive postprandial hepatic glucose release. Postprandial hyperglycemia was exacerbated by the lack of an appropriate increase in glucose uptake whether measured isotopically or by forearm glucose uptake. Thus as has been proposed for fasting hyperglycemia, excessive hepatic glucose release and impaired glucose uptake are involved in the pathogenesis of postprandial hyperglycemia in patients with NIDDM.

To determine whether [2(3)H], [3(3)H], and [6(14)C]glucose provide an equivalent assessment of glucose turnover in insulin-dependent diabetes mellitus (IDDM) and nondiabetic man, glucose utilization rates were measured using a simultaneous infusion of these isotopes before and during hyperinsulinemic euglycemic clamps. In the nondiabetic subjects, glucose turnover rates determined with [6(14)C]glucose during insulin infusion were lower (P less than 0.02) than those determined with [2(3)H]glucose and higher (P less than 0.01) than those determined with [3(3)H]glucose. In IDDM, glucose turnover rates measured with [6(14)C]glucose during insulin infusion were lower (P less than 0.05) than those determined with [2(3)H]glucose, but were not different from those determined with [3(3)H]glucose. All three isotopes indicated the presence of insulin resistance. However, using [3(3)H]glucose led to the erroneous conclusion that glucose utilization was not significantly decreased at high insulin concentrations in the diabetic patients. [6(14)C] and [3(3)H]glucose but not [2(3)H]glucose indicated impairment in insulin-induced suppression of glucose production. These results indicate that tritiated isotopes do not necessarily equally reflect the pattern of glucose metabolism in diabetic and nondiabetic man.

To determine whether sulfonylureas and exogenous insulin have different effects on insulin action, we studied eight patients with non-insulin-dependent diabetes mellitus before and after three months of treatment with tolazamide and exogenous semisynthetic human insulin, using a randomized crossover design. Therapy with tolazamide and therapy with insulin resulted in similar improvement of glycemic control, as measured by a decrease in mean glycosylated hemoglobin (+/- SEM) from 9.4 +/- 0.7 percent to 7.7 +/- 0.5 percent with tolazamide and to 7.1 +/- 0.2 percent with exogenous insulin (P less than 0.01 for both comparisons). Therapy with either tolazamide or exogenous insulin resulted in a similar lowering (P less than 0.05) of postabsorptive glucose-production rates (from 2.3 +/- 0.1 to 2.0 +/- 0.2 and 1.8 +/- 0.1 mg per kilogram of body weight per minute, respectively) but not to normal (1.5 +/- 0.1 mg per kilogram per minute). Both tolazamide and exogenous insulin increased (P less than 0.05) glucose utilization at supraphysiologic insulin concentrations (from 6.2 +/- 0.7 to 7.7 +/- 0.6 mg per kilogram per minute with tolazamide and to 7.8 +/- 0.6 mg per kilogram per minute with exogenous insulin) to nondiabetic rates (7.9 +/- 0.5 mg per kilogram per minute). Neither agent altered erythrocyte insulin binding at physiologic insulin concentrations. We conclude that treatment with sulfonylureas or exogenous insulin results in equivalent improvement in insulin action in patients with non-insulin-dependent diabetes mellitus. Therefore, the choice between these agents should be based on considerations other than their ability to ameliorate insulin resistance.

Glucose turnover determined with tritiated isotopes of glucose is subject to potential error due to glucose/glucose-6-phosphate cycling and/or cycling through glycogen. To determine the extent to which these processes alter the apparent pattern of postprandial glucose metabolism, we measured glucose turnover simultaneously with [2(3)H] glucose (an isotope that minimally cycles through glycogen but is extensively detritiated during glucose/glucose-6-phosphate cycling) and [3(3)H] glucose (an isotope that is not detritiated during glucose/glucose-6-phosphate cycling but can cycle through glycogen). Glucose turnover was measured in patients with non-insulin-dependent diabetes mellitus (NIDDM) and nondiabetic subjects both before and after ingestion of a carbohydrate meal isotopically with labeled [6(14)C] glucose. In the postabsorptive state hepatic glucose appearance was higher (P less than .05) when determined with [2(3)H] glucose than with [3(3)H] glucose in the diabetic patients, but not in the nondiabetic subjects. After glucose ingestion the integrated responses of glucose appearance, systemic entry of ingested glucose, and hepatic glucose release all were higher (P less than .05) when determined with [2(3)H] glucose compared to [3(3)H] glucose in both the diabetic and nondiabetic subjects. However, the absolute difference between glucose turnover measured with [2(3)H] and [3(3)H] glucose were similar in the diabetic and nondiabetic subjects. Both isotopes provided a similar assessment of postprandial carbohydrate metabolism, indicating that either isotope can be used with equal efficacy to compare postprandial carbohydrate metabolism in patients with NIDDM and nondiabetic subjects.

Orally administered phosphate supplements are the mainstay of therapy for hypophosphatemic osteomalacia of diverse causes and are generally believed to be free from harmful side effects. Two cases are reported, however, in which long-term therapy (14 and 10 years, respectively) resulted in hypercalcemic hyperparathyroidism associated with surgically proved adenomatous hyperplasia. This complication occurred despite concomitant treatment with pharmacologic doses of vitamin D. Thus, long-term oral phosphate therapy can produce tertiary hyperparathyroidism in susceptible patients.