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Insulin glargine is a long-acting insulin analogue, with a longer duration of action and a flatter time-action profile compared with NPH insulin. These properties can be predicted to result in higher glucose levels during the night and lower glucose levels after dinner following bedtime injection of insulin glargine compared with an equal dose of NPH insulin injected at bedtime. In two large-scale clinical trials involving either insulin-naïve (426 patients treated for 1 year) or previously insulin-treated (518 patients treated for 28 weeks) patients with type 2 diabetes, comparing addition of once-daily insulin glargine or NPH insulin to oral agents, these predictions were proven to be correct. Nocturnal hypoglycaemia was reduced by 58% in insulin-naive patients and by 22% in previously insulin-treated patients, and dinner-time glucose control was significantly better with insulin glargine than with NPH insulin once daily in the study in insulin-naive patients. The 'treat-to-target study' (756 insulin-naive patients treated for 24 weeks) showed that good glycaemic control can be achieved with aggressive titration of the insulin dose with either once-daily insulin glargine or NPH insulin combined with oral agents (mean endpoint HbA(1c) was 6.96% with insulin glargine and 6.97% with NPH insulin); however, this was achieved with less variability and nocturnal hypoglycaemia with insulin glargine. These data support use of insulin glargine instead of NPH insulin for basal insulin replacement in patients with type 2 diabetes.

Background: Individuals whose platelets are resistant to the antiaggregatory effects of insulin in vitro are also resistant to the antiaggregatory effects of nitroglycerin (GTN). We have previously shown that insulin acutely diminishes central wave reflection in large arteries and that this action of insulin is blunted in insulin-resistant subjects. However, as yet, no studies have compared the haemodynamic effects of insulin and GTN on large arterial function in the same group of subjects. The aim of this study was to determine whether resistance to the haemodynamic effects of insulin is a defect specific to insulin or whether individuals resistant to the vascular actions of insulin are also resistant to GTN., Design and Results: Dose-response characteristics of insulin and GTN on the aortic waveform were determined using applanation tonometry and pulse wave analysis (PWA) in seven healthy men (age 26 +/- 1 year, BMI 25 +/- 2 kg m(-2)). Three doses of sublingual GTN (500 microg for 1, 3 or 5 min) and insulin (0.5, 1 or 2 mU kg(-1) min(-1) for 120 min) were administered on three separate occasions. Both agents dose-dependently decreased central pulse pressure and the augmentation index (AIx) without changing brachial artery blood pressure. We next compared responses to insulin (2 mU kg(-1) min(-1) for 120 min) and sublingual GTN (500 microg for 5 min) in 20 nondiabetic subjects (age 50 +/- 2 year, BMI 21.0-36.3 kg m(-2)). Again, both agents significantly decreased AIx. Although the vascular effects of insulin and GTN vascular were positively correlated [Spearman's r=0.92 (95% confidence interval 0.81-0.97), P<0.0001], the time-course for the action GTN was faster than that of insulin. Brachial systolic blood pressure remained unchanged during the insulin infusion (122 +/- 3 vs. 121 +/- 3 mmHg, 0 vs. 120 min) but aortic systolic blood pressure decreased significantly by 30 min (111 +/- 3 vs. 107 +/- 3 mmHg, 0 vs. 30 min, P<0.01). Similarly, GTN decreased aortic systolic blood pressure from 119 +/- 4 to maximally 112 +/- 3 mmHg (P<0.001) without significantly decreasing systolic blood pressure in the brachial artery., Conclusions: The effects of insulin and GTN on large arterial haemodynamics are dose-dependent and significantly correlated. The exact mechanisms and sites of action of insulin and GTN in subjects with insulin resistance remain to be established.

In conclusion, a large body of available evidence indicates that the degree of physical conditioning is an important determinant of insulin sensitivity and overall glucose tolerance. Both acute exercise and chronic physical training are associated with enhanced disposal of a glucose load. Conversely, physical inactivity leads to a deterioration in glucose tolerance. The primary tissue responsible for accelerated glucose disposal following exercise is muscle. After an acute bout of exercise, enhanced glucose transport and augmented glycogen synthesis are largely responsible for the improvement in glucose tolerance. The beneficial effects of chronic physical training on glucose metabolism appear to be explained by multiple factors, including increased muscle mass, augmented muscle blood flow and capillary area, enhanced mitochondrial oxidative enzyme capacity, and activation of the glucose transport system. Despite these well-documented effects of training on glucose metabolism, the precise role of exercise in the treatment of diabetic patients remains to be established. In insulin-dependent (type I) diabetic individuals, acute exercise has been shown to be a helpful adjunct in establishing good glycemic control. However, the role of acute exercise in helping to smooth out glycemic control in non-insulin-dependent (type II) diabetic patients has received little attention. The role of chronic physical training in the treatment of both insulin-dependent (type I) and non-insulin-dependent (type II) diabetic individuals remains to be established.

The immunoperoxidase technique was utilized to study the occurrence and localization of relaxin in malignant and nonmalignant trophoblastic disease and nontrophoblastic gynecologic cancer. Tissue specimens were studied from normal placenta at various weeks of gestation (N = 10), hydatidiform mole (N = 10), invasive mole (N = 10), choriocarcinoma (N = 10), normal endometrium (N = 28), decidua (N = 5), adenocarcinoma of the endocervix (N = 10), of the endometrium (N = 10), corpus luteum (N = 2), ovarian serous papillary cystadenocarcinoma (N = 10), and mucinous cystadenocarcinoma (N = 10). Relaxin was identified in the syncytiotrophoblast of normal placenta at all stages of gestation and also, for the first time, in hydatidiform mole, invasive mole, and choriocarcinoma. No relaxin was found in any nontrophoblastic cancer, including secretory-type adenocarcinoma. The absence of relaxin in the secretory-type endometrial adenocarcinoma is intriguing in light of the finding of relaxin in the normal secretory endometrium. The difference may be due to absence of the relaxin-producing corpus luteum in cancer patients or to loss of relaxin synthesis in the malignant endometrium. The results of this study suggest that relaxin may be synthesized by the normal syncytiotrophoblast and trophoblastic tumors, although differential absorption of relaxin produced in another site cannot be excluded.