Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mulibrey nanism is a rare autosomal recessive growth disorder with prenatal onset, including occasional progressive cardiopathy, characteristic facial features, failure of sexual maturation, insulin resistance with type 2 diabetes, and an increased risk for Wilms' tumor. Mulibrey nanism is prevalent in the Finnish population and appears extremely rare elsewhere. However, cases outside of Finland may be underdiagnosed or misdiagnosed as having the 3-M or Silver-Russell syndrome, two important differential diagnostic disorders. Here, we report the first Australian patient with mulibrey nanism, in whom the occurrence of Wilms' tumor suggested the correct diagnosis. This was confirmed by the identification of two novel mutations in tripartite motif protein 37 (TRIM37) encoding a RING finger ubiquitin E3 ligase. Both mutations, the p.Cys109Ser B-box missense mutation and the p.Glu271_Ser287del in-frame deletion in the tumor necrosis factor receptor associated factor (TRAF) domain alter the subcellular localization of TRIM37. As both the B-box and the TRAF domains are predicted to be important for mediating the protein-protein interactions, these mutations may help the understanding of the cellular interactions of TRIM37. Our findings imply the importance of early molecular diagnostics in cases of suspected mulibrey nanism and of identifying novel mutations with potential relevance for unraveling the underlying molecular pathology. Ultrasound surveillance for Wilms' tumor is recommended for children with mulibrey nanism.
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PMID:Wilms' tumor and novel TRIM37 mutations in an Australian patient with mulibrey nanism. 1710 Sep 91

Lymphangioleiomyomatosis (LAM), is an uncommon, progressive, cystic lung disease which predominantly affects young women of childbearing age. Our patient is a 36-year-old female diagnosed with LAM by open lung biopsy in January 1995. Her past history included a spontaneous left-sided pneumothorax in June 1994 which required chest tube for resolution. The last episode occurred on October. 2002. A chest CT scan at this time presented multiple cystic lesions. Followup with pulmonary function studies every 6 months since 1997 have shown a decrease in force expiratory volume in 1 second (%FEV 1) from 100% to an actual of 53%. The force volume capacity (%FVC) decreased from 105% to 85%, with a FEV1/FVC ratio of 49%. The patient's past medical history also includes a Wilm's tumor, resulting in left nephrectomy at age 6, left adnexal abscess requiring surgery in 2002, complicated with iliac and femoral vein thrombophlebitis and left iliac artery stenosis. A small pericardial effusion occurred in 2003, which resolved spontaneously. Osteoporosis of the spine was documented with a T score of -4.9. A hysterectomy was performed during her first gestation in 1992 due to the presence of ruptured ovarian cysts. She required blood transfusions during this intervention, acquiring chronic hepatitis C infection. She has two brothers and three sisters. One brother and one sister have bronchial asthma; her paternal grandfather had stomach cancer and her grandmother was diagnosed with type II diabetes mellitus. No family history of pulmonary disorders was identified. The chest CT scan showeds many small lung cavities compatible with moderate LAM. Our patient is one of three patients living in Puerto Rico who is currently followed by the NIH sponsored LAM registry.
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PMID:A clinico-pathologic presentation of a 23-year old-female with lymphangioleiomyomatosis and Wilm's tumor. 1961 May 58

Adipose tissue releases bioactive mediators called adipokines. This review focuses on the effects of omentin, vaspin, cardiotrophin-1, Tumor necrosis factor-like Weak Inducer of Apoptosis (TWEAK) and nephroblastoma overexpressed (NOV/CCN3) on obesity and diabetes. Omentin is produced by the stromal-vascular fraction of visceral adipose tissue. Obesity reduces omentin serum concentrations and adipose tissue secretion in adults and adolescents. This adipokine regulates insulin sensitivity, but its clinical relevance has to be confirmed. Vaspin is produced by visceral and subcutaneous adipose tissues. Vaspin levels are higher in obese subjects, as well as in subjects showing insulin resistance or type 2 diabetes. Cardiotrophin-1 is an adipokine with a similar structure as cytokines from interleukin-6 family. There is some controversy regarding the regulation of cardiotrophin-1 levels in obese -subjects, but gene expression levels of cardiotrophin-1 are down-regulated in white adipose tissue from diet-induced obese mice. It also shows anti-obesity and hypoglycemic properties. TWEAK is a potential regulator of the low-grade chronic inflammation characteristic of obesity. TWEAK levels seem not to be directly related to adiposity, and metabolic factors play a critical role in its regulation. Finally, a strong correlation has been found between plasma NOV/CCN3 concentration and fat mass. This adipokine improves insulin actions.
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PMID:Role of Omentin, Vaspin, Cardiotrophin-1, TWEAK and NOV/CCN3 in Obesity and Diabetes Development. 2880 83

Normal human physiology is dependent on a tight control of the fasting blood glucose (FBG) levels. The islets of pancreas maintains FBG levels within a narrow range of 4-6mmol/L by secreting various hormones, especially insulin and glucagon. However, the hormone secretions by the islets of pancreas are governed by a collective effort among pancreas-islet axis, brain-islet axis, liver-islet axis, gut-islet axis, and adipocyte/myocyte-islet axis. Furthermore, the damage of pancreas, vascular system, brain, liver, intestine, adipose, muscle, and other organs and tissues might affect FBG levels through insulin resistance or impaired insulin signaling, which is the hallmark of type 2 diabetes. In this study, 320,572 clinical lab test results of FBG levels from healthy individuals and patients with 64 different types of diseases during the past 5 years in our hospital were retrieved and analyzed. Based on the mean (SD), median, and p (-Log10p) values, we found 57/64 diseases including type 2 diabetes, pancreatitis, diabetic nephropathy, and pancreatic cancer had significantly (p<0.05, -Log10p>1.30) increased whereas 6/64 diseases including preeclampsia, Wilms' tumor, and lupus erythematous had significantly decreased FBG levels compared to that of healthy controls. These data indicated that the increased FBG levels might be a general pathophysiological property of diseased tissues or organs and the increased FBG levels might be a consequence but not the cause for either prediabetes or type 2 diabetes.
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PMID:Fasting blood glucose levels in patients with different types of diseases. 3090 57

Serum glycated albumin (GA) level is used along with that of glucose and glycated hemoglobin (HbA1c) as indicators of glycemic control for diabetic patients. Although serum GA levels are affected by blood glucose level, they are also influenced by serum albumin metabolism and other pathological conditions. However, a systematic comparison of the serum GA levels in different types of human diseases has not been reported. In current study, 86,319 clinical lab test results of GA levels from healthy individuals and patients with 57 different types of diseases during the past 5 years in our hospital were retrieved and analyzed. Based on the mean (SD), median, and p (-Log10p) values, we found 29/57 diseases including type 2 diabetes, diabetic nephropathy, uremia, pancreatic cancer, liver cancer, hepatic encephalopathy, and azotemia had significantly (p<0.05, -Log10p>1.30) increased GA levels whereas 18/57 diseases including nephrotic syndrome, preeclampsia, Wilms' tumor, lupus erythematosus, and sepsis had significantly decreased GA levels compared to that of healthy controls. Moreover, the highest -Log10p values (>100) were observed in nephrotic syndrome, type 2 diabetes, preeclampsia, coronary heart disease, uremia, acute cerebral infarction, leukemia, and cerebrovascular disease in a descending order. These data indicated that the serum GA levels could be increased or decreased significantly in a disease-specific manner. Revealing the molecular mechanisms underlying these observations might make the increased or decreased serum GA levels indicators for different types of diseases, especially as an indicator that distinguishes nephrotic syndrome from other types of kidney diseases.
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PMID:Glycated albumin level is significantly decreased in patients suffering nephrotic syndrome. 3090 59

Purpose: Aniridia is a rare congenital eye disease, characterized by a constellation of symptoms including hypoplastic irides, foveal hypoplasia, early cataract, corneal stem cell deficiency, and glaucoma. Large chromosomal deletions spanning the PAX6 gene cause WAGR syndrome (Wilms tumor, aniridia, genitourinary anomalies, and intellectual disability [formerly called mental retardation]). We describe clinical and genetic studies of a three-generation pedigree with aniridia along with additional systemic conditions (morbid obesity, diabetes) suggesting the possibility of a contiguous-gene syndrome like WAGR.Methods: Clinical records were obtained and DNA was prepared from blood samples from three of the four patients and tested for mutations in the coding sequences of the PAX6 gene. The index patient also had cardiomyopathy and was tested for known cardiomyopathy genetic mutations using a next-generation DNA sequencing assay.Results: We discovered a novel intragenic PAX6 mutation, a 16 bp heterozygous deletion c.203delCCAGGGCAATCGGTGG, with Sanger sequencing that is the likely cause of autosomal dominant aniridia in this pedigree. This PAX6 deletion causes a frameshift in predicted protein translation and a subsequent premature termination, p.Pro68Leufs*6. The PAX6 deletion was detected in all three available family members with aniridia, the index patient, his mother, and his maternal aunt but was not observed in the Exome Aggregation Consortium (ExAC) database. Targeted sequencing of known cardiomyopathy genes in the index patient identified a second mutation, a 1.7 Mp deletion that spans the MYBPC3 gene.Conclusions: We report a pedigree with aniridia and other systemic abnormalities that were initially suspicious for a contiguous-gene syndrome like WAGR. However, genetic analysis of the pedigree revealed two independent genetic abnormalities on chromosome 11p: 1) a novel PAX6 mutation, and 2) a large chromosome deletion spanning MYBPC3, a known cardiomyopathy gene. It is unclear if morbid obesity and type II diabetes mellitus have a related genetic cause.
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PMID:Novel Intragenic PAX6 Deletion in a Pedigree with Aniridia, Morbid Obesity, and Diabetes. 3136 67