Abstract:
:The adipocyte-derived hormone adiponectin seems to protect from insulin resistance, a key factor in the pathogenesis of type 2 diabetes. Genome-wide scans have mapped a susceptibility locus for type 2 diabetes and the metabolic syndrome to chromosome 3q27, where the adiponectin gene is located. A common silent T-G exchange in nucleotide 94 (exon 2) of the adiponectin gene has been associated with increased circulating adiponectin levels. Metabolic abnormalities associated with the G allele have not been reported. We therefore assessed whether this polymorphism alters insulin sensitivity and/or measures of obesity using the Tübingen Family Study database (prevalence of the G allele, 28%). In 371 nondiabetic individuals, we found a significantly greater BMI in GG + GT (25.5 +/- 0.7 kg/m(2)) compared with TT (24.1 +/- 0.3 kg/m(2); P = 0.02). Insulin sensitivity (determined by euglycemic clamp, n = 209) was significantly lower in GG + GT (0.089 +/- 0.007 units) compared with TT (0.112 +/- 0.005 units; P = 0.02). This difference disappeared completely on adjustment for BMI. Because our population contains a relatively high proportion of first-degree relatives of patients with type 2 diabetes, we stratified by family history (FHD). Much to our surprise, the genotype differences in BMI and insulin sensitivity in the whole population were attributable entirely to differences in the subgroup without FHD, whereas in the subgroup with FHD, the G allele had absolutely no effect. Moreover, individuals without FHD had a significantly lower BMI than individuals with FHD (25.2 +/- 0.4 vs. 26.2 +/- 0.5 kg/m(2); P = 0.01), which was not the case for the GG + GT subgroup without FHD (27.0 +/- 0.9 kg/m(2); NS). This suggests that in individuals without familial predisposition for type 2 diabetes, the adiponectin polymorphism may mildly increase the obesity risk (and secondarily insulin resistance). In contrast, in individuals who are already burdened by other genetic factors, this small effect may be very hard to detect.
journal_name
Diabetesjournal_title
Diabetesauthors
Stumvoll M,Tschritter O,Fritsche A,Staiger H,Renn W,Weisser M,Machicao F,Häring Hdoi
10.2337/diabetes.51.1.37subject
Has Abstractpub_date
2002-01-01 00:00:00pages
37-41issue
1eissn
0012-1797issn
1939-327Xjournal_volume
51pub_type
杂志文章相关文献
DIABETES文献大全abstract::To evaluate possible advantages of human insulin of recombinant DNA origin (HI) in the treatment of diabetic patients, we compared cellular and humoral immunoreactivities of HI and porcine insulin (PI). Anti-insulin IgE bound equal amounts of 125I-HI and 125I-PI. There was no difference between HI- and PI-stimulated l...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.32.6.516
更新日期:1983-06-01 00:00:00
abstract:OBJECTIVE:Aging increases the risk of developing impaired glucose tolerance (IGT) and type 2 diabetes. It has been proposed that increased reactive oxygen species (ROS) generation by dysfunctional mitochondria could play a role in the pathogenesis of these metabolic abnormalities. We examined whether aging per se (in s...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db11-0121
更新日期:2011-08-01 00:00:00
abstract:OBJECTIVE:Islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP), now known as G6PC2, is a major target of autoreactive T cells implicated in the pathogenesis of type 1 diabetes in both mice and humans. This study aimed to determine whether suppression of G6p2 gene expression might therefore prev...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db11-0220
更新日期:2011-11-01 00:00:00
abstract::This article presents a model for the HLA effect in insulin-dependent diabetes mellitus (IDDM) that is almost the mirror image of a model suggested by Nepom. In the Nepom model, the products of certain HLA alleles are associated with IDDM because they bind and present a specific peptide or peptides so as to induce an ...
journal_title:Diabetes
pub_type: 杂志文章,评审
doi:10.2337/diab.41.2.123
更新日期:1992-02-01 00:00:00
abstract::Human fetal pancreatic glands were obtained from 12 consecutive prostaglandin-induced abortions. Explants cultured for 1 day were frozen at 0.3 degree C/min in a 1 M DMSO-containing medium and stored at -196 degrees C. After storage for 3-4 mo the frozen material was rapidly thawed and cultured 1 day before being test...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.31.3.238
更新日期:1982-03-01 00:00:00
abstract::The objective of the U.K. Prospective Diabetes Study is to determine whether improved blood glucose control in type II diabetes will prevent the complications of diabetes and whether any specific therapy is advantageous or disadvantageous. The study will report in 1998, when the median duration from randomization will...
journal_title:Diabetes
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:
更新日期:1995-11-01 00:00:00
abstract:OBJECTIVE:To determine whether the obesity-related decrement in fatty acid oxidation (FAO) in primary human skeletal muscle cells (HSkMC) is linked with lower mitochondrial content and whether this deficit could be corrected via overexpression of peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db09-1704
更新日期:2010-06-01 00:00:00
abstract::Neonatal morbidity was assessed in the offspring of 878 mothers with gestational diabetes mellitus (GDM), 132 mothers with pre-GDM, and 380 control subjects. Compared with the control group, the GDM group had a higher incidence of complications, including macrosomia, hypoglycemia, hyperbilirubinemia, hypocalcemia, pol...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.40.2.s74
更新日期:1991-12-01 00:00:00
abstract:OBJECTIVE:Recently, several drugs have been shown to exert beneficial effects for metabolic syndrome through mild regulation of mitochondrial function. Hence, we explored a strategy of targeting mitochondrial function to improve glucose and lipid metabolism. RESEARCH DESIGN AND METHODS:Mitochondrial membrane potential...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db09-0223
更新日期:2010-01-01 00:00:00
abstract::The human leukocyte antigen (HLA) class II genotype DQA1*0301-DQB1*0302/DQA1*0501-DQB1*0201 has been identified as a marker strongly predisposing to insulin-dependent diabetes mellitus (IDDM) in Caucasian populations. Its frequency in control populations (1-3%) is still, however, 1 order of magnitude higher than the p...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.44.5.527
更新日期:1995-05-01 00:00:00
abstract::Rats with chronic streptozotocin (SZ) diabetes develop dilatation of the alimentary tract, loss of fecal consistency, and autonomic neuropathy involving unmyelinated axons of the extrinsic innervation of the small bowel. Diabetic autonomic neuropathy involving the ileal mesenteric nerves is characterized by modest to ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.32.6.532
更新日期:1983-06-01 00:00:00
abstract::We studied the cross-sectional relationship between HbA1c and cardiovascular disease (CVD) in the survivors of the original cohort of the Framingham Heart Study (n = 1045). HbA1c was significantly related to prevalent CVD among women but not men. HbA1c was also related to hypertension and to the ratio of total to high...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.41.2.202
更新日期:1992-02-01 00:00:00
abstract::We examined the effects of aldose reductase inhibition (ARI) on glomerular filtration rate (GFR), albuminuria, and kidney histology in partially insulin-treated streptozocin-induced diabetic (STZ-D) rats. After 1 mo of diabetes, GFR was elevated over control values in the STZ-D rats but was not affected by treatment w...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.38.8.981
更新日期:1989-08-01 00:00:00
abstract::Patients with type 2 diabetes respond poorly to treatments for peripheral arterial disease (PAD) and are more likely to present with the most severe manifestation of the disease, critical limb ischemia. The underlying mechanisms linking type 2 diabetes and the severity of PAD manifestation are not well understood. We ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db16-0387
更新日期:2016-09-01 00:00:00
abstract:OBJECTIVE:Physiologically elevated insulin concentrations promote access of macromolecules to skeletal muscle in dogs. We investigated whether insulin has a stimulating effect on the access of macromolecules to insulin-sensitive tissues in humans as well. RESEARCH DESIGN AND METHODS:In a randomized, controlled trial, ...
journal_title:Diabetes
pub_type: 杂志文章,随机对照试验
doi:10.2337/db07-0238
更新日期:2007-09-01 00:00:00
abstract::Hyperinsulinemia is commonly associated with obesity, but it has not been determined which defect comes first. Some have proposed that hyperinsulinemia may precede obesity in populations prone to NIDDM, such as Pima Indians or Pacific Islanders. In contrast, longitudinal studies in adults show that insulin sensitivity...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.46.8.1341
更新日期:1997-08-01 00:00:00
abstract::The monoclonal antibodies 2H4 (anti-CD45RA) and UCHL1 (anti-CD45RO) were used to subdivide the CD4 and CD8 T-cell subsets into naive and memory cells. The peripheral blood lymphocytes of 34 patients with recent-onset IDDM, 21 patients with long-standing IDDM, and healthy control subjects of similar age and sex were an...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.42.1.127
更新日期:1993-01-01 00:00:00
abstract::Signaling pathways activated by leptin in metabolically important organs have largely been studied only in animal and/or cell culture studies. In this study, we examined whether leptin has similar effects in human peripheral tissues in vivo, ex vivo, and in vitro and whether the response would be different in lean and...
journal_title:Diabetes
pub_type: 临床试验,杂志文章
doi:10.2337/db14-0625
更新日期:2015-03-01 00:00:00
abstract::It is well described that excessive lipid metabolism can cause insulin resistance in both animals and humans, and this has been implicated as a causative factor in the development of insulin resistance and type 2 diabetes in humans. Recently, we have shown that intravenous lipid emulsion (liposyn) infusion during a 12...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.51.6.1907
更新日期:2002-06-01 00:00:00
abstract::Increased hepatic gluconeogenesis maintains glycemia during fasting and has been considered responsible for elevated hepatic glucose output in type 2 diabetes. Glucose derived periportally via gluconeogenesis is partially taken up perivenously in perfused liver but not in adult rats whose mothers were protein-restrict...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.52.6.1326
更新日期:2003-06-01 00:00:00
abstract::Capillary endothelial cells are thought to limit the transport of insulin across the endothelium, resulting in attenuated insulin action at target sites. Whether endothelial insulin transport is altered in dysglycemic insulin-resistant states is not clear and was therefore investigated in the JCR:LA-cp corpulent male ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.49.5.803
更新日期:2000-05-01 00:00:00
abstract::Alterations in renal function and structure are found even at the onset of diabetes mellitus. Studies performed over the last decade now allow definition of a series of stages in the development of renal changes in diabetes. Such a classification may be useful both in clinical work and in research activities. Stage 1 ...
journal_title:Diabetes
pub_type: 杂志文章,评审
doi:10.2337/diab.32.2.s64
更新日期:1983-05-01 00:00:00
abstract::Cardiac failure is a major cause of death in patients with type 2 diabetes, but the molecular mechanism that links diabetes to heart failure remains unclear. Insulin resistance is a hallmark of type 2 diabetes, and insulin receptor substrates 1 and 2 (IRS1 and IRS2) are the major insulin-signaling components regulatin...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db13-0095
更新日期:2013-11-01 00:00:00
abstract::Fetuin-A interferes with insulin action in animal studies, but data on fetuin-A and diabetes risk in humans are sparse and the role of nonalcoholic fatty liver disease in this association is unknown. From 2000 to 2006, we prospectively identified 470 matched incident diabetes case-control pairs in the Nurses' Health S...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db12-0372
更新日期:2013-01-01 00:00:00
abstract:OBJECTIVE:The molecular mechanisms responsible for pancreatic β-cell dysfunction in type 2 diabetes remain unresolved. Increased expression of the helix-loop-helix protein Id1 has been found in islets of diabetic mice and in vitro models of β-cell dysfunction. Here, we investigated the role of Id1 in insulin secretion ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db11-0083
更新日期:2011-10-01 00:00:00
abstract::It is often stated that type 1 diabetes results from a complex interplay between varying degrees of genetic susceptibility and environmental factors. While agreeing with this principal, our desire is that this Perspectives article will highlight another complex interplay potentially associated with this disease involv...
journal_title:Diabetes
pub_type: 杂志文章,评审
doi:10.2337/db08-0331
更新日期:2008-10-01 00:00:00
abstract::Insulin resistance and dysregulation of free fatty acid (FFA) metabolism are core defects in type 2 diabetic (T2DM) and obese normal glucose tolerant (NGT) individuals. Impaired muscle mitochondrial function (reduced ATP synthesis) also has been described in insulin-resistant T2DM and obese subjects. We examined wheth...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db13-1130
更新日期:2014-08-01 00:00:00
abstract::Pulsatile insulin secretion in vivo is believed to be derived, in part, from the intrinsic glucose-dependent intracellular calcium concentration ([Ca2+]i) pulsatility of individual islets. In isolation, islets display fast, slow, or mixtures of fast and slow [Ca2+]i oscillations. We show that the period of islet [Ca2+...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.54.12.3517
更新日期:2005-12-01 00:00:00
abstract::The minor hemoglobins AIa, AIb, and AIc were studied in mice with either genetic or chemically induced diabetes. Hemoglobin AIc was elevated approximately twofold in all the phenotypically diabetic mice studied (C57BL/KsJ-db/db, C57BL/KsJ-ob/ob, C57BL/6J-db/db, and alloxan- and streptozotocin-treated mice). Elevation ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.25.1.1
更新日期:1976-01-01 00:00:00
abstract::Uncoupling protein 1+ beige adipocytes are dynamically regulated by environment in rodents and humans; cold induces formation of beige adipocytes, whereas warm temperature and nutrient excess lead to their disappearance. Beige adipocytes can form through de novo adipogenesis; however, how "beiging" characteristics are...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db17-0296
更新日期:2017-12-01 00:00:00