A kilonova as the electromagnetic counterpart to a gravitational-wave source.

Gravitational waves were discovered with the detection of binary black-hole mergers and they should also be detectable from lower-mass neutron-star mergers. These are predicted to eject material rich in heavy radioactive isotopes that can power an electromagnetic signal. This signal is luminous at optical and infrared wavelengths and is called a kilonova. The gravitational-wave source GW170817 arose from a binary neutron-star merger in the nearby Universe with a relatively well confined sky position and distance estimate. Here we report observations and physical modelling of a rapidly fading electromagnetic transient in the galaxy NGC 4993, which is spatially coincident with GW170817 and with a weak, short γ-ray burst. The transient has physical parameters that broadly match the theoretical predictions of blue kilonovae from neutron-star mergers. The emitted electromagnetic radiation can be explained with an ejected mass of 0.04 ± 0.01 solar masses, with an opacity of less than 0.5 square centimetres per gram, at a velocity of 0.2 ± 0.1 times light speed. The power source is constrained to have a power-law slope of -1.2 ± 0.3, consistent with radioactive powering from r-process nuclides. (The r-process is a series of neutron capture reactions that synthesise many of the elements heavier than iron.) We identify line features in the spectra that are consistent with light r-process elements (atomic masses of 90-140). As it fades, the transient rapidly becomes red, and a higher-opacity, lanthanide-rich ejecta component may contribute to the emission. This indicates that neutron-star mergers produce gravitational waves and radioactively powered kilonovae, and are a nucleosynthetic source of the r-process elements.

Early Magnesium Treatment After Aneurysmal Subarachnoid Hemorrhage: Individual Patient Data Meta-Analysis.

BACKGROUND AND PURPOSE: Delayed cerebral ischemia (DCI) is an important cause of poor outcome after aneurysmal subarachnoid hemorrhage (SAH). Trials of magnesium treatment starting <4 days after symptom onset found no effect on poor outcome or DCI in SAH. Earlier installment of treatment might be more effective, but individual trials had not enough power for such a subanalysis. We performed an individual patient data meta-analysis to study whether magnesium is effective when given within different time frames within 24 hours after the SAH. METHODS: Patients were divided into categories according to the delay between symptom onset and start of the study medication: <6, 6 to 12, 12 to 24, and >24 hours. We calculated adjusted risk ratios with corresponding 95% confidence intervals for magnesium versus placebo treatment for poor outcome and DCI. RESULTS: We included 5 trials totaling 1981 patients; 83 patients started treatment<6 hours. For poor outcome, the adjusted risk ratios of magnesium treatment for start <6 hours were 1.44 (95% confidence interval, 0.83-2.51); for 6 to 12 hours 1.03 (0.65-1.63), for 12 to 24 hours 0.84 (0.65-1.09), and for >24 hours 1.06 (0.87-1.31), and for DCI, <6 hours 1.76 (0.68-4.58), for 6 to 12 hours 2.09 (0.99-4.39), for 12 to 24 hours 0.80 (0.56-1.16), and for >24 hours 1.08 (0.88-1.32). CONCLUSIONS: This meta-analysis suggests no beneficial effect of magnesium treatment on poor outcome or DCI when started early after SAH onset. Although the number of patients was small and a beneficial effect cannot be definitively excluded, we found no justification for a new trial with early magnesium treatment after SAH.

A multi-tiered intervention to address behavioural and cognitive changes after diagnosis of primary brain tumour: a feasibility study.

PURPOSE: Untreated behavioural and cognitive changes after primary brain tumour (PBT) can result in challenging behaviours (CBs), with limited documentation on treatment approaches. This study explored the feasibility of employing a Behavioural Consultancy approach to manage CBs, targeting individuals with PBT, family and treating staff. METHODS: Participants were patients and families of two hospitals and health professionals from cancer/neurological services. A single-case experimental design piloted skill-based training and environmental changes in managing socio-behavioural impairments in a person with a low grade astrocytoma. A half-day workshop to train family members (n = 7) in compensatory strategy use to manage CBs after PBT was piloted. Finally, a 1-day workshop was provided to 43 health professionals in managing CBs after PBT. For both workshops, a pre-post impact evaluation was conducted employing a purpose-designed Strategies Use Measure. RESULTS: All three interventions demonstrated positive results. The single case showed a 71% decrease in the target behaviour (time spent talking) post-intervention. Some attrition to these gains was observed at two follow-up time points (3 and 5 months). Participants from both workshops demonstrated significant post-intervention increases in perceived knowledge of Strategy Use (family members z = 2.03, p < 0.05; health professionals z = 4.95, p < 0.00; Wilcoxon signed-rank test). CONCLUSIONS: These initial studies highlight the potential of employing an integrated multi-tiered intervention based on a Behavioural Consultancy model to manage CBs after PBT.

Assessment of insulin action in insulin-dependent diabetes mellitus using [6(14)C]glucose, [3(3)H]glucose, and [2(3)H]glucose. Differences in the apparent pattern of insulin resistance depending on the isotope used.

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.

Postprandial hyperglycemia in patients with noninsulin-dependent diabetes mellitus. Role of hepatic and extrahepatic tissues.

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.

The cost of treating type 2 diabetes (CODEIRE).

Diabetes mellitus is the most common chronic metabolic disease and a major source of morbidity and mortality. Type 2 diabetes (T2D) is by far the most prevalent form of diabetes accounting for around 90% of cases worldwide. In recent years it has become apparent that a diabetes epidemic is unfolding as a result of increasing obesity, sedentary lifestyles and an ageing population. The enormity of the diabetes epidemic raises concern about the total cost to healthcare systems. This study was undertaken to investigate the direct healthcare costs of managing T2D in Ireland. Data was captured on 701 diabetes patients attending four diabetes centres. A bottom-up, prevalence-based design was used, which collected data on hospital resource use and clinical outcome measures over a 12-month period (1999/2000). The study was observational in nature, focusing on usual care of patients with T2D. Although the true prevalence of T2D in Ireland is unknown, conservative estimates are 3.9% for diagnosed diabetes and 6% for both diagnosed and undiagnosed diabetes. Using these figures the annual total direct cost was estimated at 377.2 million euro for diagnosed diabetes and 580.2 million euro for both diagnosed and undiagnosed diabetes. This corresponds to 4.1% and 6.4% of total healthcare expenditure respectively. Hospitalisations were the main driver of costs, accounting for almost half of overall costs, while ambulatory and drug costs accounted for 27% and 25% respectively. Hospitalisation costs were high because 60% of patients had developed complications. The most common microvascular and macrovascular complications were neuropathy and angina respectively. The annual cost of care for patients with microvascular and macrovascular complications were 1.8 and 2.9 times the cost of treating those without clinical evidence of complications respectively. The figure for patients with both types of complications was 3.8. This study shows that T2D is a very costly disease, largely due to the cost of and the management of complications. Many diabetes related complications are preventable, therefore it would appear a cost-effective approach for government to invest in the prevention of T2D and diabetes related complications.

The role of autoregulation of the hepatic glucose production in man. Response to a physiologic decrement in plasma glucose.

In man, a decrease in plasma glucose concentration results in a compensatory increase in hepatic glucose release. Studies in vitro have suggested that a low glucose concentration per se may directly stimulate hepatic glucose release, an effect often referred to as autoregulation. Whether autoregulation occurs in man in response to a physiologic decrement in blood glucose is not known. Therefore, seven healthy, nonobese subjects were studied on two occasions to determine the role of autoregulation in mediating the increase in glucose production that accompanies a physiologic decrement in plasma glucose concentration. On both occasions, plasma glucose concentrations were clamped successively at 95, 65, and 95 mg/dl for 2 h each. Insulin (approximately 14 microU/ml) and glucagon (approximately 70 pg/ml) were maintained constant on both occasions by an infusion of somatostatin and insulin. Phentolamine and propranolol also were infused on one occasion to produce combined alpha- and beta-adrenergic blockade. In the absence of adrenergic blockade, glucose production increased by approximately 1.3 mg/kg X min when the plasma glucose concentration was decreased from 95 to 65 mg/dl and decreased by approximately 1.5 mg/kg X min when glucose was increased from 65 to 95 mg/dl. In the presence of adrenergic blockade, the increase and decrease in glucose production averaged 0 and 0.5 mg/kg X min, respectively, representing 70-100% inhibition. We conclude that, in the presence of low physiologic insulin concentrations, autoregulation is not a major contributor to the hepatic response to a physiologic decrement in plasma glucose concentration in man.

Effects of hyperglycemia on glucose production and utilization in humans. Measurement with [23H]-, [33H]-, and [614C]glucose.

Studies with tritiated isotopes of glucose have demonstrated that hyperglycemia per se stimulates glucose utilization and suppresses glucose production in humans. These conclusions rely on the assumption that tritiated glucose provides an accurate measure of glucose turnover. However, if in the presence of hyperglycemia the isotope either loses its label during "futile" cycling or retains its label during cycling through glycogen, then this assumption is not valid. To examine this question, glucose utilization and glucose production rates were measured in nine normal subjects with a simultaneous infusion of [23H]glucose, an isotope that may undergo futile cycling but does not cycle through glycogen; [614C]glucose, an isotope that may cycle through glycogen but does not futile cycle; and [33H]glucose, an isotope that can both undergo futile cycling and cycle through glycogen. In the postabsorptive state at plasma glucose concentration of 95 mg X dl-1, glucose turnover determined with [614C]glucose (2.3 +/- 0.1 mg X kg-1 X min-1) was greater than that determined with [33H]glucose (2.1 +/- 0.1 mg X kg-1 X min-1, P = 0.002) and slightly less than that determined with [23H]glucose (2.7 +/- 0.2 mg X kg-1 X min-1, P = 0.08). Plasma glucose was then raised from 95 to 135 to 175 mg X dl-1 while insulin secretion was inhibited, and circulating insulin, glucagon, and growth hormone concentrations were maintained constant by infusion of these hormones and somatostatin. Glucose production and utilization rates determined with [614C]glucose continued to be less than those determined with [23H]glucose and greater than those seen with [33H]glucose.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of tolazamide and exogenous insulin on pattern of postprandial carbohydrate metabolism in patients with non-insulin-dependent diabetes mellitus. Results of randomized crossover trial.

To determine whether therapy with exogenous insulin or sulfonylureas results in a postprandial pattern of carbohydrate metabolism in patients with non-insulin-dependent diabetes mellitus (NIDDM) that resembles that in nondiabetic individuals, we employed a dual-isotope technique combined with forearm catheterization to examine meal disposition in NIDDM patients, before and after 3 mo of therapy with tolazamide and after 3 mo of therapy with exogenous insulin, with a randomized crossover design. Results were compared with those observed in nondiabetic subjects. Although both forms of therapy improved chronic glycemic control (glycosylated hemoglobin concentration went from 9.6 +/- 0.7 to 7.6 +/- 0.5 and 7.1 +/- 0.2%, respectively, P less than .01), exogenous insulin resulted in a lower postprandial glycemic response than tolazamide (P less than .001). Both agents comparably increased (P less than .01) fasting and integrated postprandial insulin concentrations. However, the initial rate of postprandial increase was greater with exogenous insulin (P less than .05). Tolazamide (P less than .05) but not exogenous insulin increased postprandial C-peptide concentrations. However, tolazamide did not improve the deficient early insulin release. Both agents (P less than .05) lowered postabsorptive hepatic glucose release (from 2.8 +/- 0.3 to 2.3 +/- 0.2 mg . kg-1 . min-1), but not to normal rates (1.8 +/- 0.1 mg . kg-1 . min-1).(ABSTRACT TRUNCATED AT 250 WORDS)

Development of hypercalcemic hyperparathyroidism after long-term phosphate supplementation in hypophosphatemic osteomalacia. Report of two cases.

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.

Large-scale screening by the automated Wassermann reaction.

In view of the drawbacks in the use of the Kahn test for large-scale screening of blood donors, mainly those of human error through work overload and fatiguability, an attempt was made to adapt an existing automated complement-fixation technique for this purpose. This paper reports the successful results of that adaptation.

Congenital dyserythropoietic anaemia type II (HEMPAS): a family study.

A family having two affected siblings with congenital dyserythropoietic anaemia type II (HEMPAS) is described. The proband was diagnosed after referral for investigation of haemolytic anaemia. Clinical evaluation and in vivo red cell (RBC) survival and the sequestration studies in the proband indicated that the anaemia was due to a combination of ineffective erythropoiesis and premature destruction of RBCs in the spleen. Scanning electron microscopic examination of peripheral RBCs was undertaken and is reported. The polypeptide composition of RBC membranes was also examined using polyacrylamide gel electrophoresis after solubilisation in sodium dodecyl sulphate. These results are also reported.

Insulin action in non-insulin-dependent diabetes mellitus: the relationship between hepatic and extrahepatic insulin resistance and obesity.

To determine the contribution of obesity to the insulin resistance of non-insulin-dependent diabetes mellitus, insulin dose response curves for suppression of glucose production and stimulation of glucose utilization were generated in lean and obese diabetic patients and compared to those observed in weight-matched nondiabetic subjects. Glucose utilization during 0.4, 1.0, and 10.0 mU/kg x min insulin infusions (producing insulin concentrations ranging from approximately 50 to 2,000 microU/mL) was lower (p less than .02 to .001) in lean and obese diabetic patients compared to weight-matched nondiabetic subjects indicating insulin resistance. Glucose utilization was not correlated with obesity in the diabetic subjects. Suppression of glucose production was impaired (P less than .03 and .001) in both the lean and obese diabetic subjects at physiologic but not supraphysiologic insulin concentrations. We conclude that patients with NIDDM have both hepatic and extrahepatic insulin resistance, the severity of which appears to be independent of the degree of obesity.

Assessment of the postprandial pattern of glucose metabolism in nondiabetic subjects and patients with non-insulin-dependent diabetes mellitus using a simultaneous infusion of [2(3)H] and [3(3)H] glucose.

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.

Prevalence of diabetic retinopathy in patients with diabetes mellitus diagnosed after the age of 70 years.

AIMS/BACKGROUND: A hospital based prevalence study was undertaken to estimate the prevalence of diabetic retinopathy (DR) in patients diagnosed as having diabetes mellitus after the age of 70 years. The prevalence of visually threatening retinopathy at the time of diagnosis of diabetes was also determined. The association between prevalence of DR and duration of diabetes mellitus, mode of treatment, HbA1c levels, presence of hypertension, and sex of patient was examined and a comparison was drawn between this study and earlier prevalence studies of DR in older type II diabetics. METHODS: Using data on the Irish Diabetic Retinopathy Register located in the Mater Misericordiae Hospital, Dublin, all patients who were diagnosed as having type II diabetes mellitus after the age of 70 years were invited to attend for ophthalmic review. Medical records were examined to determine the duration of diabetes mellitus, mode of treatment, recent HbA1c levels, and the presence of systemic hypertension. RESULTS: Of the 150 patients examined, 21 (14%) had some form of DR and 10 of these patients (6.6%) had visually threatening retinopathy or previously treated visually threatening retinopathy. Five patients (3.3%) presented with visually threatening retinopathy at the time of diagnosis of diabetes. Those patients with DR had a significantly higher median duration of diabetes (5.0 years) compared with those patients without DR (3.5 years). A significantly higher proportion of patients with DR required treatment with insulin and a correspondingly lower proportion of patients without DR were controlled on diet alone. There was no significant association between prevalence of DR and HbA1c levels, systemic hypertension, or sex of patient. There was a lower overall prevalence of DR in comparison with earlier studies. CONCLUSIONS: The prevalence of DR in these elderly type II diabetics is lower than than previously reported in patients with type II disease but a small percentage of patients had visually threatening retinopathy at presentation. Longer duration of diabetes and insulin use were associated with a significantly increased prevalence of DR. All elderly type II diabetic patients require thorough ophthalmic examination near to the time of first presentation and thereafter at regular intervals.

Diabetic retinopathy in Down's syndrome.

AIM: To determine the prevalence of diabetic retinopathy in patients with Down's syndrome and diabetes mellitus. METHODS: Nine patients with Down's syndrome and diabetes mellitus were assessed. Factors recorded included type and duration of diabetes, level of diabetic control, blood pressure, urinalysis, and results of ophthalmological examination. RESULTS: The duration of diabetes ranged from 8 to 41 years (mean 17.6 years). All had satisfactory glycaemic control and blood pressure measurements on the low side of normal (mean 106.6/70 mm Hg). One patient had early background diabetic retinopathy. The remainder had no evidence of diabetic retinopathy. CONCLUSION: The low prevalence of diabetic retinopathy in these Down's syndrome patients, despite the long duration, is an interesting finding. It suggests some inherent protective factor against the development of diabetic retinopathy in this patient subgroup.

Insulin: either alone or combined with oral hypoglycemic agents.

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.

Fine needle aspiration cytology of thyroid nodules: review of 36 months experience.

Studies suggest that fine needle aspiration of thyroid nodules is a sensitive and specific tool for the detection of thyroid cancers thus preventing unnecessary operations. This technique was introduced in our institution in 1987 and performed where indicated under strictly defined criteria. We reviewed the aspirates performed over a 36 month period to critically evaluate the role of this procedure. Review was limited to F.N.A.s of nodules considered to be potentially malignant by conventional criteria and hence all the following criteria needed to be fulfilled: (1) solitary or dominant nodules in a multinodular goitre, (2) cold on isotope scanning, (3) solid or complex cystic nodule on ultrasonography. During the period May 1987 to May 1990 88 aspiration procedures were performed on 77 patients. 93% of the 77 patients had adequate aspirates and of these approximately 30% were considered suspicious or malignant. The overall resection rate was 23.4% which is approximately one third of the rate expected should suspicion have been based solely on conventional imaging criteria. The yield of neoplasia (adenoma and carcinoma) at resection was 89%. We found FNA to be a very useful adjunct in the management of nodular thyroid disease when used in conjunction with clinical laboratory and radiological evaluation. It is safe, inexpensive and provides useful additional information towards making appropriate decisions in an area beset with uncertainty.

Efficacy of combination therapy in non-insulin dependent diabetes mellitus.

Secondary failure of oral hypoglycaemic agents raises the dilemma of whether to institute therapy with insulin alone, or in combination. We reviewed our experience of combination therapy following secondary failure of oral hypoglycaemic therapy. Seventeen subjects were receiving combination therapy for 6 months or more. Such treatment was associated with a significant fall in HbA1C--from 10.7 +/- 0.38 per cent to 8.3 +/- 0.35 per cent (p < 0.01) after 6 months and remained significantly reduced at 12 months (8.7 +/- 0.34 per cent (p < 0.01)). Mean body weight, systolic and diastolic blood pressure were unchanged during treatment with adjuvant insulin therapy. Insulin therapy is a useful adjunct in the daily management of subjects with NIDDM who experience secondary failure of oral hypoglycaemic agents.