Primary Defects in ��-Cell Function Further Exacerbated by Worsening of Insulin Resistance Mark the Development of Impaired Glucose Tolerance in Obese Adolescents

OBJECTIVE—Impaired glucose tolerance (IGT) is a pre-diabetic state of increasing prevalence among obese adolescents. The purpose of this study was to determine the natural history of progression from normal glucose tolerance (NGT) to IGT in obese adolescents.RESEARCH DESIGN AND METHODS—We determined the evolution of β-cell function, insulin sensitivity (S_I), and glucose tolerance in a multiethnic group of 60 obese adolescents over the course of approximately 30 months. Each subject underwent three serial 3-h oral glucose tolerance tests. Dynamic, static, and total β-cell responsivity (Φ_d, Φ_s, and Φ_tot, respectively) and S_i were assessed by oral C-peptide and glucose minimal models. The disposition index (DI), which adjusts insulin secretion for S_i, was calculated.RESULTS—At baseline, all 60 subjects had NGT. Seventy-seven percent (46 subjects) maintained NGT over the three testing periods (nonprogressors), whereas 23% (14 subjects) developed IGT over time (progressors). At baseline, percent fat and BMI Z score were comparable between the groups. Fasting plasma glucose, 2-h glucose, glucose area under the curve at 180 min, and Φ_d were significantly different between the two groups at baseline, whereas S_i was comparable between the two groups. Over time, although S_i remained unchanged in nonprogressors, it steadily worsened by ∼45% (P > 0.04) in progressors. β-Cell responsivity decreased by 20% in progressors, whereas it remained stable in nonprogressors. The DI showed a progressive decline in progressors compared with a modest improvement in nonprogressors (P = 0.02).CONCLUSIONS—Obese adolescents who progress to IGT may manifest primary defects in β-cell function. In addition, progressive decline in S_i further aggravates β-cell function, contributing to the worsening of glucose intolerance.Understanding the underlying putative metabolic defects leading to the development of type 2 diabetes requires studies that focus on the earliest stages of the disease before the onset of any alterations in glucose tolerance. In adults, type 2 diabetes is the final stage in the progression of the disease (1–3), characterized by a progressive worsening in both insulin resistance and secretion (4–7). Whether a similar profile also occurs in youth developing type 2 diabetes is unknown. Much of the understanding of type 2 diabetes in youth originates from cross-sectional studies performed in obese adolescents with overt disease (8) or with impaired glucose tolerance (IGT) (9,10). One longitudinal study in obese adolescents with IGT at baseline indicated that over a period of 23 months, 45% reverted to normal glucose tolerance (NGT), 30% maintained IGT, and 25% developed type 2 diabetes(11). Thus, youth with IGT are at high risk for developing type 2 diabetes because of the presence of both insulin resistance and β-cell dysfunction.To assess the metabolic sequence of events that might be implicated in the transition from NGT to IGT, we performed serial oral glucose tolerance tests (OGTTs) along with anthropometric measures in a group of obese adolescents over a period of approximately 3 years. Using the oral minimal model (OMM) (12,13), we determined β-cell responsivity (Φ), insulin sensitivity (S_i), and disposition index (DI) and thus have repeated measures of both insulin secretion and insulin action before and during the evolution of IGT in obese adolescents. In a longitudinal study, we tested the hypothesis that preexisting β-cell dysfunction, further exacerbated by a progressive worsening in S_i, characterizes the onset of IGT in childhood obesity.     

Summary overview of human gene therapy trials in the U.S.

It has been approximately six and one-half yearssince the first patient was enrolled in a gene therapyclinical trial. Since that important begining, this typeof genetic intervention has grown into a worldwideinvestigative activity involving about 2100 patients asof December 1996. Although it was initially thought     

Nursing visibility: could the I.C.N.P. help?

The present article discusses the visibility of Nursing care through the use of a Nursing classification "International Classification of Nursing Practice, proposed by the International Council of Nurses (ICN). The usefulness of a specific classification is discussed and comparison with the medical classifications are reasoned. Examples of experimentation are brought for sustaining the utility of the ICNP in the clinical practice, in education, in the Nursing management and in politics. To have a common language world-wide sustains the development of the discipline and the empowerment of Nursing profession.     

Significance of anesthesiology and intensive care in the development of reconstructive surgery (as exemplified by the scientific school of the Academician B.V. Petrovskiĭ)

B. V. Petrovsky, the creator of one of the leading surgical schools, realized, that surgery cannot develop without anesthesiological and resuscitation support. He actively promoted measures which ensured rapid transformation of such branches as anesthesia and postoperative care into independent disciplines. Introduction of neuroleptanalgesia, high-quality artificial ventilation of the lungs, prolonged regional and combined anesthesia, protection of the myocardium and brain, bronchofibroscopy, extracorporeal detoxication, assisted circulation, and computer monitoring allowed the performance of the most sophisticated interventions on the heart, aorta, lungs, esophagus, liver and bile duct, and peripheral vessels. Progress in anesthesiology and reanimatology promoted the development of new trends in reconstructive surgery, such as repair microsurgery, organ transplantation, endovascular and endoscopic surgery.     

Defects in the prostaglandin system. V. Inherited (?) disorder of prostacyclin degradation in the plasma (Wien-D?bling defect)

The case report is presented of a woman of child-bearing age who developed myocardial infarction. An extremely shortened in vitro half-life of PGI2 in plasma was detected in this patient. This new familial defect "Wien-D?bling", in the prostaglandin system might affect an essential coregulator of haemostatic balance in man. It is not known whether this short half-life of PGI2 in vitro is due to accelerated degradation or a failure in stabilization of this biologically active compound.