Comparison of pancreas-transplanted type 1 diabetic patients with portal-venous versus systemic-venous graft drainage: impact on glucose regulatory hormones and the growth hormone/insulin-like growth factor-I axis.

Context: Pancreas grafts can be drained through the iliac vein (systemic drainage) or the portal vein.

Objective: We hypothesized that normalization of portal insulin in patients with portal pancreas graft drainage stimulates the GH/IGF-I axis and thereby contributes to glucose control.

Methods: We compared patients after combined kidney and pancreas transplantation with portal drainage (n = 7) to patients with systemic drainage of the pancreas graft (n = 8) and nondiabetic controls (n = 8).

Plasma alpha-defensin is associated with cardiovascular morbidity and mortality in type 1 diabetic patients.

Context: alpha-Defensins are antimicrobial peptides of the innate immune system. In addition, experimental evidence suggests that alpha-defensins are proatherogenic.

Objective: The objective of the study was to examine the predictive value of plasma alpha-defensin as a clinical marker of cardiovascular disease (CVD) in patients with type 1 diabetes.

Variation in the ADIPOQ gene promoter is associated with carotid intima media thickness independent of plasma adiponectin levels in healthy subjects.

Aims: The ADIPOQ gene encodes the protein adiponectin, and decreased circulating adiponectin levels have been observed in cardiovascular disease. We investigated the role of the ADIPOQ gene single-nucleotide polymorphisms (SNPs) A-11426G, G-11391A, C-11377G, and T45G with plasma adiponectin levels and common carotid artery intima media thickness (IMT) in a cohort of healthy subjects participating in the RISC (Relationship between Insulin Sensitivity and Cardiovascular disease) study.

Methods And Results: Anthropometric and metabolic assessment and B-mode ultrasound of the carotid IMT were measured in 1306 subjects [589 men; 717 women, mean +/- SD age 43.

Early elective insulin therapy can reduce hyperglycemia and increase insulin-like growth factor-I levels in very low birth weight infants.

Objective: To investigate the use of insulin throughout the first week of life in very low birth weight (VLBW) infants (birth weight <1.5 kg) to improve glucose control and increase insulin-like growth factor-I (IGF-I) levels. IGF-I is the dominant hormone involved in fetal growth, and low levels have been implicated in neonatal morbidities, such as retinopathy of prematurity.

Increased levels of alpha-defensin (-1, -2 and -3) in type 1 diabetic patients with nephropathy.

Objective: Diabetic nephropathy is associated with low-grade inflammation and activation of the complement system. Defensins, as part of the innate immune system, may play a regulatory role in the complement cascade and may also augment the production of proinflammatory cytokines. The aim of this study was therefore to elucidate whether alpha-defensin is associated with diabetic nephropathy, low-grade inflammation and lipid profiles.

Fetal growth velocity, size in early life and adolescence, and prediction of bone mass: association to the GH-IGF axis.

Unlabelled: Poor growth in early life is associated with numerous adverse outcomes later in life. In 123 adolescents 16-18 yr of age, the previous findings of a positive relation between size in early life and later bone mass was confirmed. These associations were mediated by the current height and weight, but it was not confirmed that alterations of the GH-IGF axis cause this.

Assessing the potential usefulness of IGF-related peptides and adiponectin for predicting disease risk.

Objective: Insulin-like growth factors (IGF), their binding proteins and adiponectin have been investigated as potential blood-based biomarkers for a variety of diseases. Before these circulating proteins can be considered as biomarkers, their variation within and between individuals and between published studies must be critically assessed. The purpose of this study was to use the D-value to predict the potential usefulness of IGF-related peptides and adiponectin as biomarkers for the diagnosis of colorectal cancer (CRC).

Total and high molecular weight (HMW) adiponectin levels and measures of glucose and lipid metabolism following pioglitazone treatment in a randomized placebo-controlled study in polycystic ovary syndrome.

Objective: Recent studies suggested that the effect of adiponectin on insulin-stimulated glucose metabolism is mediated primarily by the high molecular weight (HMW) form of adiponectin. In the present study we evaluated total and HMW adiponectin in polycystic ovary syndrome (PCOS) patients and controls and examined possible mechanisms for increased insulin sensitivity during pioglitazone treatment.

Study Subjects: Thirty PCOS patients randomized to pioglitazone, 30 mg/day, or placebo for 16 weeks and 14 weight-matched healthy females were studied.

Phenotypic effects of null and haploinsufficiency of acid-labile subunit in a family with two novel IGFALS gene mutations.

Context: IGF-I deficiency may result from impairment of GH secretion or action, or from defects in IGF-I synthesis, transport, or action. Complete deficiency of the acid-labile subunit (ALS), previously described in two male patients, the only known inherited alteration in IGF-I transport, is characterized by severe circulating IGF-I and IGF binding protein (IGFBP)-3 deficiency with only mild growth retardation.

Objective: Our objective was to study the characterization, at biochemical and molecular levels, of the cause for severe circulating IGF-I and IGFBP-3 deficiency in a male patient with mild growth retardation.

Hypoadiponectinemia is associated with insulin resistance and glucose intolerance after renal transplantation: impact of immunosuppressive and antihypertensive drug therapy.

The objectives of this analysis were (1) to assess whether low serum adiponectin concentrations are associated with insulin resistance, metabolic syndrome, and new-onset posttransplantation diabetes mellitus (PTDM) and (2) to examine the possible effects of immunosuppressive and antihypertensive therapies on circulating adiponectin levels after renal transplantation. A total of 172 consecutive previously nondiabetic renal transplant recipients were examined 3 mo after transplantation, the majority (n = 167) with an oral glucose tolerance test. Serum adiponectin was measured by an in-house time-resolved immunofluorometric assay.

Concomitant, specific determination of growth hormone and pegvisomant in human serum.

Growth hormone (GH) and the GH receptor blocker, pegvisomant are usually circulating in high concentration in pegvisomant treated acromegalic patients. This and the close similarity between the peptides make determination of either difficult. In the present methodological study, endogenous GH in serum is initially isolated and determined in a slightly modified commercial immunometric assay, whereafter the now GH free medium allows measurement of pegvisomant.

The insulin-like growth factor (IGF) system and its relation to infliximab treatment in adult patients with Crohn's disease.

Objective: Metabolic bone disease (MBD) and muscle wasting (MW) are serious complications in adult patients suffering from inflammatory bowel disease. These complications may be caused by alterations in the insulin-like growth factor (IGF) system. The aim of the present study was to assess changes in the IGF system in patients with active Crohn's disease (CD) before and during infliximab treatment.

Utility of free IGF-I measurements.

For nearly 30 years, the endogenous bioactivity of insulin-like growth factor I (IGF-I) has been estimated by its circulating concentrations of immunoreactive IGF-I, obtained after either removal or inactivation of the IGF-binding proteins (IGFBPs), and today serum/plasma total IGF-I serves as a useful parameter in the diagnosis and clinical control of growth hormone (GH) disorders. Different assays for the measurement of free, unbound IGF-I were introduced more than a decade ago. Nevertheless, this measurement remains controversial, and in daily clinical practice serum total IGF-I has retained its position as the most widely used IGF-related measurement in GH disorders.

Bioactive insulin-like growth factor (IGF) I and IGF-binding protein-1 in anorexia nervosa.

Context: Regulation of IGF-I activity appears crucial in anorexia nervosa (AN) during adaptation to chronic starvation as well as during the regenerative processes on nutritional restoration.

Objective: The objective of this study was to examine the relationship between IGF-I bioactivity and IGF-binding capacity as expressed as formation of the binary complex of IGF-binding protein-1 (IGFBP-1) and IGF-I in patients with AN at different stages and with different subtypes of the disease.

Design: This was a longitudinal study.

The effects of sex steroid replacement therapy on an expanded panel of IGF-related peptides.

Background: Oral estrogen alone (EA) decreases concentrations of total IGF-I while increasing IGFBP-1, but data on other IGF-related peptides are inconsistent and/or sparse. Combined oral estrogen and progestin (EP) may have differential effects on IGF-related peptides dependent on its progestin-associated androgenic activity. The aim of this study was to clarify these relationships, as circulating IGF-related peptides are potential surrogates of predisposition to common chronic diseases.

[Medical co-treatment af acromegaly with a somatostatin analogue and a growth hormone receptor antagonist].

We tested the effect of co-treatment of acromegaly with a somatostatin analogue (SA) and a growth hormone receptor antagonist (GHA). Eleven patients underwent: 1) conventional treatment with SA, 2) discontinued treatment, 3) 6 weeks treatment with GHA (10 mg), 4) 6 weeks treatment with GHA (15 mg), 5) 3 months combined SA and GHA. Circulating IGF-I was lowered by GHA and more so with combined treatment.

Hypoglycemia due to paraneoplastic secretion of insulin-like growth factor-I in a patient with metastasizing large-cell carcinoma of the lung.

Context: Nonpancreatic tumors may cause recurrent hypoglycemia known as nonislet cell tumor hypoglycemia. It is due to overproduction and secretion by the tumor of incompletely processed IGF-II, termed big IGF-II. We recently identified a patient with recurrent hypoglycemia and low insulin, but without elevated big IGF-II.

Gender differences of oligomers and total adiponectin during puberty: a cross-sectional study of 859 Danish school children.

Context: Pubertal stages have been shown to influence total adiponectin (ADPN) levels. Furthermore, testosterone has been shown to alter the isomer distribution of ADPN.

Objective: The goal of this study was to investigate whether pubertal stages and testosterone levels influenced total serum ADPN levels and the distribution of ADPN isomers.

Normal growth spurt and final height despite low levels of all forms of circulating insulin-like growth factor-I in a patient with acid-labile subunit deficiency.

Background: In a recently described patient with acid-labile subunit (ALS) deficiency, the inability to form ternary complexes resulted in a marked reduction in circulating total insulin-like growth factor (IGF)-I, whereas skeletal growth was only marginally affected. To further study the role of circulating versus locally produced IGF-I in skeletal growth in this patient, we now describe in detail growth changes and their relationship with several components of the circulating IGF system.

Design And Methods: We followed growth and development up to the final height in a patient with complete ALS deficiency and determined both spontaneous and growth hormone (GH)-stimulated changes in the IGF system, including measurements of total, free and bioactive IGF-I, total IGF-II and insulin-like growth factor binding protein (IGFBP)-1, IGFBP-2 and IGFBP-3.

The insulin-like growth factor (IGF)-system in active ulcerative colitis and Crohn's disease: relations to disease activity and corticosteroid treatment.

Background: Metabolic bone disease (MBD) and muscle wasting (MW) are serious complications in adults suffering from inflammatory bowel disease (IBD). The inflammatory process and corticosteroid treatment may lead to changes in the IGF-system associated with MBD and MW.

Aim: To assess changes in the IGF-system and clinical and biochemical markers in ulcerative colitis (UC) and Crohn's disease (CD).

Elevated circulating adiponectin in type 1 diabetes is associated with long diabetes duration.

Objective: To study circulating adiponectin concentrations in relation to diabetes duration and endogenous insulin secretion in patients with type 1 diabetes.

Patients: Patients with haemoglobin A1c (HbA1c) < 6% (reference range 3.6-5.

Serum adiponectin is a predictor of coronary heart disease: a population-based 10-year follow-up study in elderly men.

Context: Cross-sectional and nested case-control studies indicate a relationship between adiponectin, obesity, and coronary heart disease (CHD).

Objective: Our objective was to investigate whether adiponectin could predict CHD in a population-based cohort of elderly men.

Design And Setting: From 1991-1995 a baseline investigation was carried out in 832 healthy men aged 70 yr in the Uppsala Longitudinal Study of Adult Men (ULSAM study).

The GH-IGF-IGFBP axis is changed in Turner syndrome: partial normalization by HRT.

Background: We recently described increased insulin-like growth factor binding protein 3 (IGFBP-3) proteolysis in the circulation in adult Turner syndrome (TS), with normalization during sex hormone replacement therapy (HRT), suggesting the presence of a sex hormone regulated IGFBP-3 proteolytic activity.

Objective: To study the GH-IGF-IGFBP axis in TS without and during HRT, and to further characterize the nature of the IGFBP-3 proteolytic activity.

Material: 23 women with TS before and during HRT, and 24 healthy age-matched women.

Plasma adiponectin levels in relation to carotid intima media thickness and markers of insulin resistance.

Background: Circulating adiponectin is a marker for insulin sensitivity, derived from fat cells. It is largely unknown if adiponectin is also an independent marker for early atherosclerosis.

Methods And Results: Plasma adiponectin levels were measured in 373 men and 514 women of middle-age by a time-resolved immunofluorometric assay.

Body composition is distinctly altered in Turner syndrome: relations to glucose metabolism, circulating adipokines, and endothelial adhesion molecules.

Background: Body composition in Turner syndrome (TS) is altered with final height of TS decreased; anthropometry and bone mass distinctly changed.

Aim: To describe total and regional distribution of fat and muscle mass in TS and the relation to measures of glucose metabolism, sex hormones, IGFs, and markers of inflammation and vascular function.

Material And Methods: Fifty-four women with TS (mean age, 42.