scholarly journals A Novel Point Mutation in the Insulin Gene Giving Rise to Hyperproinsulinemia*

1997 ◽  
Vol 82 (5) ◽  
pp. 1629-1631 ◽  
Author(s):  
Margaret G. Warren-Perry ◽  
Susan E. Manley ◽  
Diane Ostrega ◽  
Ken Polonsky ◽  
Sandra Mussett ◽  
...  
Keyword(s):  
Point Mutation ◽  
Plasma Insulin ◽  
Direct Sequencing ◽  
Insulin Level ◽  
Insulin Gene ◽  
Normal Range ◽  
A Chain ◽  
The Uk ◽  
Processing Protease

Abstract A 58-yr-old obese white Caucasian male type 2 diabetic, entered into the UK Prospective Diabetes Study, was found to have raised fasting total proinsulin levels 708 pmol/L−1 (normal range, 3–16 pmol/L−1) and normal specific plasma insulin level 29 pmol/L−1 (normal range, 21–75 pmol/L−1). Immunoreactive plasma insulin, measured by RIA, was 503 pmol/L−1. DNA was extracted, the insulin gene amplified by the PCR, and by direct sequencing, a novel point mutation, G1552C, was identified, which resulted in the substitution of proline (CCT) for arginine (CGT) at position 65. This prevented cleavage of the C-peptide A-chain dibasic cleavage site (lys-arg) by the processing protease in the pancreatic β-cells. The plasma proinsulin and insulin levels were in accord with expression of both the wild-type and the mutant alleles. The G1552C mutation was not linked with diabetes, because it was present in a 37-yr-old nondiabetic daughter and not in a 35-yr-old daughter who had had gestational diabetes.

scholarly journals A point mutation in the albumin gene in a Chinese patient with familial dysalbuminemic hyperthyroxinemia

1999 ◽  
pp. 374-378 ◽  
Author(s):  
KT Tang ◽  
HJ Yang ◽  
KB Choo ◽  
HD Lin ◽  
SL Fang ◽  
...  
Keyword(s):  
Point Mutation ◽  
Serum Proteins ◽  
Direct Sequencing ◽  
Chinese Patient ◽  
Normal Range ◽  
Step Method ◽  
Japanese Family ◽  
Albumin Gene ◽  
First Case ◽  
Euthyroid Hyperthyroxinemia

Familial dysalbuminemic hyperthyroxinemia (FDH) is an autosomal dominant disorder characterized by euthyroid hyperthyroxinemia. However, FDH has not been reported in Chinese or African patients. Here, we report the first case of FDH in a Chinese patient. A 69-year-old Chinese man was found to have increased serum total T(4) concentrations (198-242nmol/l; normal range 58-148nmol/l) and free T(4) concentrations (>58pmol/l; T(4) analog method, normal range 9-28pmol/l). Serum total T(3) and TSH concentrations were normal. The patient was misdiagnosed as hyperthyroid and was later suspected to have a TSH-producing tumor by the finding of a pituitary microadenoma, which was eventually proven to be a non-functional pituitary 'incidentaloma'. Electrophoretic analysis of the patient's serum proteins demonstrated enhanced albumin binding of [(125)I]T(4). Serum free T(4) concentrations were normal (16-19pmol/l, normal range 9-26pmol/l) when a two-step method was used. Direct sequencing of the albumin gene showed a guanine to adenosine transition in the second nucleotide of codon 218, resulting in a substitution of histidine (CAC) for the normal arginine (CGC) in one of the two alleles in the patient. The point mutation was further confirmed by HphI digestion of exon 7 of the albumin gene. The patient's son was not affected. Our studies demonstrated that the point mutation of the albumin gene in a Chinese patient with FDH was similar to that found in western white families, but differed from that in a Japanese family in whom a guanine to cytosine transition at the same position was found.

scholarly journals Metabolic Implications of Hepatitis C Virus Infection and it's Correlation to Steatohepatitis in Chronic Hepatitis C Patients with and without Type 2 Diabetes

2010 ◽  
Vol 3 ◽  
pp. IDRT.S3935
Author(s):  
Howaida Elsayed Mansour ◽  
Hanan Mohamed Farouk ◽  
Maryam Ahmad Abdurrahman ◽  
Afaf Abdelaleem Mostafa ◽  
Iman M. Aly Hassan ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Hepatitis C ◽  
Plasma Insulin ◽  
Insulin Level ◽  
Hcv Infection ◽  
Plasma Insulin Level ◽  
Chronic Hcv Infection ◽  
Chronic Hcv

Background Chronic hepatitis C virus (HCV) infection is not a simple viral infection; it has many metabolic and autoimmune complications. Objective To investigate the impacts of chronic HCV infection on glucose and lipid metabolism and its correlation-if any-with body mass index (BMI) and hepatosteatosis in chronic HCV patients. Patients and Methods One hundred and three (103) chronic HCV patients were involved in this study. After blood sugar testing patients were classified into three groups; Group I: 68 chronic HCV patients with type 2 diabetes. Group II: 35 chronic HCV patients without Type 2 Diabetes and Group III: 25 patients with Type 2 Diabetes as a control group. With informed written consents and approval from Ain Shams medical ethics committee, all groups were subjected to the following: full history taking, thorough clinical examination, calculation of BMI, and measurement of the waist/hip ratio were done. Assessment of fasting plasma insulin level was done by the immune-enzymatic method. Assessment of the insulin resistance state was done by Homeostatic Model Assessment (HOMA-IR). Detection of anti-HCV was done by the 3rd generation ELISA test and confirmed by qualitative polymerase chain reaction (PCR). Results Diabetic and non diabetic chronic HCV patients were found to have significantly higher fasting plasma insulin levels and insulin resistance states than the control group. This insulin resistance was not due to increased body mass index as there was a non significant difference in BMI between all the studied groups. Positive correlations were found between plasma insulin level, liver enzymes and steatohepatitis in HCV patients whether they were diabetic or not. No correlation was found between BMI and plasma insulin level in group II patients (HCV only). Conclusion Chronic HCV infection may be regarded as an independent risk factor for the development of insulin resistance and type 2 diabetes. HCV induces insulin resistance; the key step for glucose intolerance, and virus C induced steatohepatitis therefore leading to faster progression to cirrhosis. The impacts of chronic HCV infection on glucose and lipid metabolism should be recognized in clinical care centers and addressed in future studies.

scholarly journals Gambling problems in bipolar disorder in the UK: Prevalence and distribution

2015 ◽  
Vol 207 (4) ◽  
pp. 328-333 ◽  
Author(s):  
Lisa Jones ◽  
Alice Metcalf ◽  
Katherine Gordon-Smith ◽  
Liz Forty ◽  
Amy Perry ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Problem Gambling ◽  
Severity Index ◽  
Gambling Problems ◽  
Rapid Cycling ◽  
Probable Significance ◽  
History Of ◽  
Gambling Severity ◽  
The Uk

BackgroundNorth American studies show bipolar disorder is associated with elevated rates of problem gambling; however, little is known about rates in the different presentations of bipolar illness.AimsTo determine the prevalence and distribution of problem gambling in people with bipolar disorder in the UK.MethodThe Problem Gambling Severity Index was used to measure gambling problems in 635 participants with bipolar disorder.ResultsModerate to severe gambling problems were four times higher in people with bipolar disorder than in the general population, and were associated with type 2 disorder (OR = 1.74, P = 0.036), history of suicidal ideation or attempt (OR = 3.44, P = 0.02) and rapid cycling (OR = 2.63, P = 0.008).ConclusionsApproximately 1 in 10 patients with bipolar disorder may be at moderate to severe risk of problem gambling, possibly associated with suicidal behaviour and a rapid cycling course. Elevated rates of gambling problems in type 2 disorder highlight the probable significance of modest but unstable mood disturbance in the development and maintenance of such problems.

scholarly journals Serum urate and cardiovascular events in the DCCT/EDIC study

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Alicia J. Jenkins ◽  
Barbara H. Braffett ◽  
Arpita Basu ◽  
Ionut Bebu ◽  
Samuel Dagogo-Jack ◽  
...  
Keyword(s):  
Cardiovascular Events ◽  
Serum Urate ◽  
Continuous Variable ◽  
Major Adverse Cardiovascular Events ◽  
Normal Range ◽  
The Metabolic Syndrome ◽  
Routine Measurement

AbstractIn type 2 diabetes, hyperuricemia is associated with cardiovascular disease (CVD) and the metabolic syndrome (MetS), but associations in type 1 diabetes (T1D) have not been well-defined. This study examined the relationships between serum urate (SU) concentrations, clinical and biochemical factors, and subsequent cardiovascular events in a well-characterized cohort of adults with T1D. In 973 participants with T1D in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study (DCCT/EDIC), associations were defined between SU, measured once in blood collected 1997–2000, and (a) concurrent MetS and (b) incident ‘any CVD’ and major adverse cardiovascular events (MACE) through 2013. SU was higher in men than women [mean (SD): 4.47 (0.99) vs. 3.39 (0.97) mg/dl, respectively, p < 0.0001], and was associated with MetS features in both (men: p = 0.0016; women: p < 0.0001). During follow-up, 110 participants (11%) experienced “any CVD”, and 53 (5%) a MACE. Analyzed by quartiles, SU was not associated with subsequent CVD or MACE. In women, SU as a continuous variable was associated with MACE (unadjusted HR: 1.52; 95% CI 1.07–2.16; p = 0.0211) even after adjustment for age and HbA1c (HR: 1.47; 95% CI 1.01–2.14; p = 0.0467). Predominantly normal range serum urate concentrations in T1D were higher in men than women and were associated with features of the MetS. In some analyses of women only, SU was associated with subsequent MACE. Routine measurement of SU to assess cardiovascular risk in T1D is not merited.Trial registration clinicaltrials.gov NCT00360815 and NCT00360893.

scholarly journals Determinants of penetrance and variable expressivity in monogenic metabolic conditions across 77,184 exomes

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Julia K. Goodrich ◽  
Moriel Singer-Berk ◽  
Rachel Son ◽  
Abigail Sveden ◽  
Jordan Wood ◽  
...  
Keyword(s):  
Case Control Study ◽  
Rare Variants ◽  
Standard Of Care ◽  
Polygenic Scores ◽  
Monogenic Diseases ◽  
Metabolic Conditions ◽  
The Uk ◽  
Control Study ◽  
Polygenic Variation

AbstractHundreds of thousands of genetic variants have been reported to cause severe monogenic diseases, but the probability that a variant carrier develops the disease (termed penetrance) is unknown for virtually all of them. Additionally, the clinical utility of common polygenetic variation remains uncertain. Using exome sequencing from 77,184 adult individuals (38,618 multi-ancestral individuals from a type 2 diabetes case-control study and 38,566 participants from the UK Biobank, for whom genotype array data were also available), we apply clinical standard-of-care gene variant curation for eight monogenic metabolic conditions. Rare variants causing monogenic diabetes and dyslipidemias display effect sizes significantly larger than the top 1% of the corresponding polygenic scores. Nevertheless, penetrance estimates for monogenic variant carriers average 60% or lower for most conditions. We assess epidemiologic and genetic factors contributing to risk prediction in monogenic variant carriers, demonstrating that inclusion of polygenic variation significantly improves biomarker estimation for two monogenic dyslipidemias.

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