We studied the effects of GH administration on myocardial structure and function in 20 patients with hypopituitarism (14 males and 6 females; mean +/- SE age, 47.2 +/- 2.6 yr; range, 31-59 yr) developed in adulthood because of pituitary or parapituitary tumors. All patients had GH deficiency (GHD), as assessed by a GH response of less than 4 micrograms/L to a standard insulin tolerance test (0.05 U kg, iv) and the combined pyridostigmine (120 mg, orally, at -60 min) plus GHRH (1 microgram/kg, iv, at 0 min) test. Patients received either placebo (n = 10) or GH substitution therapy (n = 10; 0.05 U/kg.day GH for 1 yr; 0.03 U/kg.day during the first month). M- and B-mode echocardiography and pulsed Doppler examination of transmitral flow were performed before treatment, 6 months and 1 yr after starting GH or placebo administration, and 15 days and 3 months after GH or placebo withdrawal. Twenty healthy subjects, matched for age, sex, body mass index, and physical activity, served as controls. Left ventricular dimensions, mass, and systolic function were normal in patients with adult-onset GHD; however, diastolic function, specifically E wave deceleration time, was altered. GH administration markedly increased left ventricular performance and reversed diastolic abnormalities at 6 and even more so at 12 months. On the other hand, a clear increase in left ventricular mass was seen after 12, but not after 6, months of GH administration (P < 0.01 vs. pretreatment values). In addition, although all changes induced by GH treatment disappeared within 3 months after GH withdrawal, at that time the increase in left ventricular mass was still detectable (P < 0.05 vs. pretreatment values). These data indicate that augmented left ventricular contractility is not strictly related to cardiac muscle growth, supporting the hypothesis that GH treatment increases the inotropic activity of myocardial fibers. In conclusion, GH treatment enhances cardiac function, increases cardiac mass, and reverses diastolic abnormalities in adults with hypopituitarism and GHD. However, long term studies are required to demonstrate that GH replacement therapy reduces cardiac death rate in these patients.

This study evaluates the effects of insulin versus glibenclamide on lipoprotein metabolism at comparable levels of blood glucose control, in particular on the concentration and distribution of VLDL subfractions and lipolytic enzyme activities in nine NIDDM men (aged 56 +/- 3 years, BMI 26.5 +/- 0.9 kg/m2) (means +/- SE) participating in a crossover study. After a 3-week washout period, patients were randomly assigned to 2-month treatment periods (insulin or glibenclamide); thereafter, each patient crossed to the other treatment. At the end of each period, mean daily blood glucose (MDBG), HbA1e, plasma lipids, lipoproteins (VLDL, LDL, HDL), lipoprotein subfractions (VLDL1, 2, 3; HDL2, HDL3), and post-heparin lipase activities (lipoprotein lipase [LPL], hepatic lipase [HL]) were evaluated. Although glucose control was similar at the end of both periods (MDBG 8.3 +/- 0.3 vs. 7.9 +/- 0.3 mmol/l; HbA1c 7.4 +/- 0.3 vs. 7.0 +/- 0.2%, insulin versus glibenclamide), insulin compared with glibenclamide induced a significant reduction in plasma triglycerides (0.9 +/- 0.1 vs. 1.1 +/- 0.1 mmol/l, P < 0.05), VLDL triglycerides (50.1 +/- 12.2 vs. 63.6 +/- 12.3 mg/dl, P < 0.02), VLDL1 lipid concentration (24.9 +/- 7.5 vs. 39.9 +/- 9.5 mg/dl, P < 0.006), and increased HDL2 cholesterol (25.2 +/- 1.6 vs. 20.3 +/- 1.3 mg/dl, P < 0.03). In terms of VLDL percentage subfraction distribution, with insulin, there was a decrease in the larger subfractions (VLDL1 26.5 +/- 3.0 vs. 37.8 +/- 3.4%, P < 0.02) and an increase in the smallest (VLDL3 47.3 +/- 3.8 vs. 37.3 +/- 3.3%, P < 0.05). Moreover, HL activity was significantly lower after insulin than after glibenclamide (HL 247.2 +/- 22.3 vs. 263.5 +/- 22.6 mU/ml, P < 0.05). In conclusion, compared with glibenclamide, insulin treatment (independent of variations in glucose control) is able to decrease significantly plasma triglycerides, to increase HDL2 cholesterol, and to reduce only the concentration of the larger VLDL subfractions, with a consequent redistribution of their profile.

No abstract

Insuline pancreatique et plasmatiq ue chez le foetus de lapin au cours de la gestation.

Metabolic control, insulin secretion and insulin action were evaluated in seven Type 2 (non-insulin-dependent) diabetic patients with secondary failure to oral antidiabetic agents before and after two months of combined therapy with supper-time insulin (Ultratard: 0.4 U/kg body weight/day) plus premeal glibenclamide (15 mg/day). Metabolic control was assessed by 24 h plasma glucose, NEFA, and substrate (lactate, alanine, glycerol, ketone bodies) profile. Insulin secretion was evaluated by glucagon stimulation of C-peptide secretion, hyperglycaemic clamp (+ 7 mmol/l) and 24 h free-insulin and C-peptide profiles. The repeat studies, after two months of combined therapy, were performed at least 72 h after supper-time insulin withdrawal. Combining insulin and sulfonylurea agents resulted in a reduction in fasting plasma glucose (12.9 +/- 7 vs 10.4 +/- 1.2 mmol/l; p less than 0.05) and hepatic glucose production (13.9 +/- 1.1 vs 11.1 +/- 1.1 mumol.kg-1.min-1; p less than 0.05). Mean 24 h plasma glucose was also lower (13.7 +/- 1.2 vs 11.1 +/- 1.4 mmol/l; p less than 0.05). Decrements in fasting plasma glucose and mean 24 h profile were correlated (r = 0.90; p less than 0.01). HbA1c also improved (11.8 +/- 0.8 vs 8.9 +/- 0.5%; p less than 0.05). Twenty-four hour profile for NEFA, glycerol, and ketone bodies was lower after treatment, while no difference occurred in the blood lactate and alanine profile. Insulin secretion in response to glucagon (C-peptide = +0.53 +/- 0.07 vs +0.43 +/- 0.07 pmol/ml) and hyperglycaemia (freeinsulin = 13.1 +/- 2.0 vs 12.3 +/- 2.2 mU/l) did not change.(ABSTRACT TRUNCATED AT 250 WORDS)