Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Common uncoupling protein 2 (UCP2) promoter polymorphism -866G/A is reported to be associated with its expression in adipose tissue and the risk of obesity in Caucasians. On the other hand, several studies suggested that UCP2 expression in beta-cells is an important determinant of insulin secretion. In the Japanese population, morbid obesity is very rare, and insulin secretion capacity is relatively low as compared with Caucasians. Because UCP2 would link to insulin secretion and obesity, it might explain this ethnic difference. Here, we report that the UCP2 promoter with the A allele showed higher promoter activity in the INS-1 beta-cell line. The frequency of the A allele is higher in our Japanese study than that in Caucasians. Type 2 diabetic patients with the A allele need insulin therapy earlier and showed higher frequency of insulin treatment. Moreover glucose-induced early insulin secretion is significantly lower in patients with the A allele. However, there was no difference in allele frequency between obese and lean type 2 diabetic patients. In conclusion, UCP2 promoter polymorphism -866G/A does not affect obesity in Japanese type 2 diabetic patients but affects its transcription in beta-cells and modulates glucose-induced insulin secretion and eventually insulin requirement in Japanese type 2 diabetic patients. Higher A allele frequency in the Japanese population might partly explain the ethnic difference of insulin secretion capacity.
Diabetes 2004 Feb
PMID:Uncoupling protein 2 promoter polymorphism -866G/A affects its expression in beta-cells and modulates clinical profiles of Japanese type 2 diabetic patients. 1474 1

The genetic basis for the more common forms of human obesity predisposing to insulin resistance and development of type 2 diabetes is multigenic rather than monogenic in origin. New mouse "diabesity" models have been created by combining independent diabetes risk-conferring quantitative trait loci from two unrelated parental strains: New Zealand Obese (NZO/HlLt) and Nonobese Nondiabetic (NON/Lt). F1 hybrid males, heterozygous at all polymorphic autosomal loci distinguishing the two parental strains, are driven to obesity-induced diabetes (diabesity) at high frequencies. This review focuses on two new recombinant congenic strains (RCSs) developed by introgressing multiple NZO/HlLt chromosomal segments into the nominally diabesity-resistant NON/Lt strain background. Both RCSs gain more weight than NON animals. Although exhibiting comparable weight gain and adiposity, only one of the two RCSs develops diabetes. Hence, these two RCSs will be instructive in elucidating genetic and pathophysiological differences underlying uncomplicated obesity syndromes versus diabetogenic obesity (diabesity) syndromes. Unlike mice with null mutations in a single gene producing morbid obesity, the new models develop a more moderate obesity produced by the interaction of numerous genes with relatively small effects. These RCSs are differentially sensitive to adverse side effects of thiazolidinediones and thus should be particularly useful for pharmacogenetic analyses.
Diabetes 2004 Feb
PMID:Differential levels of diabetogenic stress in two new mouse models of obesity and type 2 diabetes. 1474 59

Morbid obesity (MO) is associated with diabetes mellitus-type II (DM-II). Roux-en Y gastric bypass (RNY) has been shown to normalize glucose intolerance in these patients through an incompletely understood mechanism. Gastrointestinal hormonal changes have been suggested as an explanation for resolution of DM II. Preoperatively, 20 MO patients with DM-II were evaluated for demographics and fasting levels of the following: glucose, insulin, C-peptide, glucagon, cortisol, gastric inhibitory polypeptide (GIP), and glucagon-like peptide-1 (GLP-1). Each patient underwent RNY with a 15-cc gastric pouch and 150-cm Roux limb. Postoperatively, each of the variables was measured at 2 weeks, 6 weeks, and 12 weeks and compared with the preoperative result using Student t test with significance, P = 0.05. Results are expressed as mean +/- SD. Twenty patients (5 male and 15 female), age 40.3 +/- 7.9 years, weight 146.3 +/- 34.0 kg, height 158.7 +/- 18.7 cm, and BMI 52.7 +/- 8.8, were enrolled in this IRB-approved protocol. Weight and BMI decreased progressively (117.5 +/- 26.9 kg and 47.0 +/- 7.4, P = 0.01, respectively) during the study but reached significance only at 12 weeks. Fasting plasma glucose decreased significantly within 2 weeks after RNY. Insulin and cortisol both approached, but never achieved, significant changes over 12 weeks. GLP-1 increased initially, but not significantly. GIP and C-peptide both decreased significantly. Glucagon remained essentially unchanged over 12 weeks. RNY rapidly normalizes fasting plasma glucose in morbidly obese patients with DM-II. GIP, a gactor in the enteroinsulin axis, decreases and may play a role in the correction of DM-II after gastric bypass.
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PMID:Hormonal changes after Roux-en Y gastric bypass for morbid obesity and the control of type-II diabetes mellitus. 1496 37

Many renal transplantation centers arbitrarily deny transplantation to patients with morbid obesity usually defined as body mass index > 35. We present a series of 173 primary renal transplant patients in a new transplant program that accepted all recipients with 3 yrs or greater life expectancy and no active malignancy or infection. When the patient outcomes are divided into groups by body mass index, it can be seen as expected that patients with body mass index > 30 have an increased prevalence of wound infections (p < 0.05). However, aside from this complication there are no statistically significant outcome differences between the three groups realizing the possibility of type II statistical error because of small numbers. Graft survival, patient survival and other surgical complications are the same in all groups regardless of body mass index. At the end of the 3-yr interval with a minimum transplant follow-up of 3 months, 169 of 173 patients were alive and 163 of 173 transplants were functioning. Based on our experience, morbid obesity should not be used to exclude patients arbitrarily from transplantation anymore than advanced age or diabetes should.
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PMID:Morbid obesity does not preclude successful renal transplantation. 1510 76

The subject is a diabetic and hypertensive woman treated early during an unplanned pregnancy with a multi-drug regimen that included three drugs with no prior history for use in pregnant women (rosiglitazone, gliclazide, atorvastatin). She was under care for chronic hypertension, which she suffered for 14 years, and diabetes mellitus, hypercholesterolemia, anxiety disorder, morbid obesity and epilepsia for 5 years. She was exposed to rosiglitazone (4mg/day), gliclazide (60mg/day), and atorvastatin (40mg/day) in addition to acarbose, spironolactone, hydrochlorothiazide, carbamazepine, thioridazine, amitryptiline, chlordiazepoxide, and pipenzolate bromide during the first 7 weeks of gestation while unaware of pregnancy. Pharmacotherapy was adjusted following clinical recognition of pregnancy during the 8th week. She gave birth to a normal healthy infant at the 36th week of gestation. This is the first reported case of human exposure to rosiglitazone, gliclazide, and atorvastatin during pregnancy. Although the normal pregnancy outcome does not address the safety of these drugs for use in pregnancy, these data contribute to a limited knowledge regarding human exposure to these antidiabetic drugs.
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PMID:Normal pregnancy outcome following inadvertent exposure to rosiglitazone, gliclazide, and atorvastatin in a diabetic and hypertensive woman. 1513 57

To ascertain whether distinct chromosomal loci existed that were linked to severe obesity, as well as to utilize the increased heritability of this excessive phenotype, we performed a genome-wide scan in severely obese French Caucasians. The 109 selected pedigrees, totaling 447 individuals, required both the proband and a sibling to be severely obese (BMI >or=35 kg/m(2)), and 84.8% of the nuclear families possessed >or=1 morbidly obese sibling (BMI >or=40). Severe and morbid obesity are still relatively rare in France, with rates of 2.5 and 0.6%, respectively. The initial genome scan consisted of 395 evenly spaced microsatellite markers. Six regions were found to have suggestive linkage on 4q, 6cen-q, 17q, and 19q for a BMI >or=35 phenotypic subset, and 5q and 10q for an inclusive BMI >or=27 group. The highest peak on chromosome 19q (logarithm of odds [LOD] = 3.59) was significant by genome scan simulation testing (P = 0.042). These regions then underwent second-stage mapping with an additional set of 42 markers. BMI >or=35 analysis defined regions on 17q23.3-25.1 and 19q13.33-13.43 with an maximum likelihood score LOD of 3.16 and 3.21, respectively. Subsequent pooled data analysis with an additional previous population of 66 BMI >or=35 sib-pairs led to a significant LOD score of 3.8 at the 19q locus (empirical P = 0.023). For more moderate obesity and overweight susceptibility loci, BMI >or=27 analysis confirmed suggestive linkage to chromosome regions 5q14.3-q21.3 (LOD = 2.68) and 10q24.32-26.2 (LOD = 2.47). Plausible positional candidate genes include NR1H2 and TULP2.
Diabetes 2004 Jul
PMID:Genome-wide linkage analysis for severe obesity in french caucasians finds significant susceptibility locus on chromosome 19q. 1522 Feb 11

Sterol regulatory element-binding protein (SREBP)-1 transcription factors play a central role in energy homeostasis by promoting glycolysis, lipogenesis, and adipogenesis. The sterol regulatory element-binding protein gene (SREBF)-1 is a good candidate gene for obesity and obesity-related metabolic traits such as type 2 diabetes and dyslipidemia. The SREBF-1 molecular screening of 40 unrelated obese patients by PCR/single-strand conformation polymorphism revealed 19 single nucleotide polymorphisms (SNPs). Six SNPs were genotyped for an association study in large French obese and nonobese cohorts. Case-control studies using two independent nonobese cohorts indicated that SNP17 (54G/C, exon 18c) is associated with morbid obesity (odds ratio 1.5, P = 0.006 and P = 0.02, respectively). SNP3 (-150G/A, exon 1a), SNP5 (-36delG, exon 1a), and SNP17 are found in high linkage disequilibrium (D' > 0.8). The haplotype including wild-type alleles of these SNPs (C/G/G/T/C/G, HAP2) is identified as a risk factor for morbid obesity (P = 0.003). In the obese group, SNP3, SNP5, and SNP17 are associated with male-specific hypertriglyceridemia (P = 0.07, P = 0.01, and P = 0.05, respectively). SNP17 is also associated with type 2 diabetes (P = 0.03) and increased prevalence of nephropathy (P = 0.028) in a diabetic cohort. Our results indicate a role of the SREBF-1 gene in genetic predisposition of metabolic diseases such as obesity, type 2 diabetes, and dyslipidemia.
Diabetes 2004 Aug
PMID:SREBF-1 gene polymorphisms are associated with obesity and type 2 diabetes in French obese and diabetic cohorts. 1527

Childhood panhypopituitarism may be acquired or congenital. Children with panhypopituitarism can present clinically with diabetes, growth failure, decreased bone density, and morbid obesity. In the forensic setting without the proper history, it can be misdiagnosed as child abuse or neglect. We report a case of a 3-year-old black girl who was admitted to the emergency room with apnea and subsequently died. While at the emergency department, it was discovered that the child had a fractured left hip and was severely growth retarded for age. The coroner wanted to rule out child abuse and/or neglect and requested an autopsy based on the physical findings identified by hospital staff. Significant findings at autopsy included small for age (15th percentile for age), hypoplastic brain/pituitary gland/adrenal gland/thyroid gland, abnormally formed skull with an occipital protuberance, a fractured left hip with decreased bone density, and central adiposity. Subsequent to the autopsy, it was discovered that at 6 weeks of age the child suffered from group B streptococci meningitis that resulted in panhypopituitarism. The panhypopituitarism then resulted in seizure activity, diabetes insipidus, and growth retardation. The authors hope this case report and review of the literature will assist investigators, pathologists, and clinicians in making a distinction between neglect or inflicted injury of child abuse and panhypopituitarism that can present with similar signs and symptoms.
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PMID:Childhood panhypopituitarism presenting as child abuse: a case report and review of the literature. 1532 73

Morbid obesity is a serious health problem associated with disease and mortality. One such disease is non-insulin-dependent diabetes mellitus (NIDDM). Approximately 95% of American diabetics have NIDDM. One of the major causes for type 2 diabetes is obesity. The improvement of diabetes with weight control is not in the earliest description of the disease. However, dietary control of NIDDM is often disappointing. Diet can improve glucose metabolism in obesity, but the improvement usually represents only a portion or a brief return to euglycemia, even when patients appear to be compliant. In contrast, reversal of NIDDM has been much more successfully achieved after bariatric surgery. Intra-abdominal fat deposition is associated with increased plasma concentration of free fatty acids, which reduce insulin sensitivity at both muscular and hepatic sites. The progression of diabetes is heralded by the inability of the beta-cells to maintain their previously high rate of insulin secretion in response to glucose, in the face of insulin resistance. The propensity to develop type 2 diabetes may be genetically determined or triggered by environmental factors. The connection between diabetes and obesity represents a continuum that progresses through different phases in which defective insulin action is the principal problem. At this point, we are unable to correlate the different findings of the many questions that arise, such as: 1) Does the decrease in sensitivity to insulin result from rearrangement of the insulin receptor? 2) Is weight loss the trigger for decrease of insulin resistance? 3) Is rearrangement of part of the intestine a mechanism to trigger the secretion of hormones (incretins) that help in insulin response? 4) Which mechanism controls the insulin resistance? The goal of this paper is to review literature on incretins and address the role of incretins after bariatric surgery. We know very little about the action of incretins in diabetes. We will assess the interaction between the secretion of incretins and bariatric surgery for the cure of diabetes.
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PMID:Are we closer to finding the treatment for type 2 diabetes mellitus in morbid obesity? Are the incretins the key to success? 1532 92

Nonalcoholic steatohepatitis (NASH) is a progressive form of nonalcoholic fatty liver disease (NAFLD) that can lead to hepatic fibrosis and cirrhosis. Portal fibrosis in the absence of NASH, called isolated portal fibrosis (IPF), has received less attention and has not been classified as a spectrum of NAFLD. The aims of this study were to determine the prevalence of IPF in subjects undergoing gastric bypass surgery, to identify biochemical variables associated with IPF, and to assess the metabolic syndrome as defined by the AdultTreatment Panel III criteria. We analyzed liver biopsies from 195 morbidly obese subjects after excluding all other causes of liver disease. The prevalence of fatty liver (FL) only, IPF, and NASH was 30.3%, 33.3%, and 36.4%, respectively. Several biochemical parameters significantly trended across the 3 groups, with IPF falling between FL and NASH. Hyperglycemia was the only metabolic parameter associated with NASH (OR, 5.4; 95% CI, 2.4-12; P < .0001) and IPF (OR, 2.8; 95% CI, 1.2-6.5; P = .01). Subjects with diabetes had the greatest risk for NASH (OR, 8; 95% CI, 3.3-19.7; P < .0001) and IPF (OR, 4.3; 95% CI, 1.6-11.6; P = .003). The metabolic syndrome was identified in 78.5% of subjects, and a significant trend for the number of metabolic criteria was observed across the spectrum of FL, IPF, and NASH. In conclusion, a significant subset of morbidly obese individuals has portal fibrosis in the absence of NASH that is associated with glycemic dysregulation. Therefore, IPF should be considered a spectrum of NAFLD that may prelude NASH in morbid obesity.
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PMID:Portal fibrosis and hepatic steatosis in morbidly obese subjects: A spectrum of nonalcoholic fatty liver disease. 1536 53


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