scholarly journals Monogenic Diabetes in Youth With Presumed Type 2 Diabetes: Results From the Progress in Diabetes Genetics in Youth (ProDiGY) Collaboration

2021 ◽  
Author(s):  
Jennifer N. Todd ◽  
Jeffrey W. Kleinberger ◽  
Haichen Zhang ◽  
Shylaja Srinivasan ◽  
Sherida E. Tollefsen ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Clinical Diagnosis ◽  
Sequence Data ◽  
Correct Diagnosis ◽  
Familial Risk ◽  
Hdl Cholesterol ◽  
Exome Sequence Data ◽  
Prediction Of Complications ◽  
Design And Methods

<p>Objective: Maturity-onset diabetes of the young (MODY) is frequently misdiagnosed as type 1 or type 2 diabetes. Correct diagnosis may result in a change in clinical treatment and impacts prediction of complications and familial risk. In this study, we aimed to assess the prevalence of MODY in multi-ethnic youth under age 20 years with a clinical diagnosis of type 2 diabetes.</p> <p> </p> <p>Research design and methods: We evaluated whole-exome sequence data of youth with a clinical diagnosis of type 2 diabetes. We considered participants to have MODY if they carried a MODY gene variant classified as likely pathogenic (LP) or pathogenic (P) according to current guidelines.</p> <p> </p> <p>Results: 93 of 3,333 participants (2.8%) carried an LP/P variant in <i>HNF4A </i>(16 participants)<i>, GCK </i>(23)<i>, HNF1A </i>(44), <i>PDX1</i> (5), <i>INS</i> (4), and <i>CEL</i> (1). Compared with those with no LP/P variants, youth with MODY had a younger age at diagnosis (12.9 ± 2.5 <i>vs</i> 13.6 ± 2.3 years, <i>P</i>=0.002) and lower fasting C-peptide levels (3.0 ± 1.7 <i>vs</i> 4.7 ± 3.5 ng/mL, <i>P</i><0.0001). Youth with MODY were less likely to have hypertension (6.9% <i>vs</i> 19.5%, <i>P</i>=0.007) and had higher HDL cholesterol (43.8 <i>vs</i> 39.7 mg/dL, <i>P=</i>0.006). </p> <p> </p> Conclusions: By comprehensively sequencing the coding regions of all MODY genes, we identified MODY in 2.8% of youth with clinically diagnosed type 2 diabetes; importantly, in 89% (n=83) the specific diagnosis would have changed clinical management. No clinical criterion reliably separated the two groups. New tools are needed to find ideal criteria to select individuals for genetic testing.

scholarly journals Monogenic Diabetes in Youth With Presumed Type 2 Diabetes: Results From the Progress in Diabetes Genetics in Youth (ProDiGY) Collaboration

2021 ◽  
Author(s):  
Jennifer N. Todd ◽  
Jeffrey W. Kleinberger ◽  
Haichen Zhang ◽  
Shylaja Srinivasan ◽  
Sherida E. Tollefsen ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Clinical Diagnosis ◽  
Sequence Data ◽  
Correct Diagnosis ◽  
Familial Risk ◽  
Hdl Cholesterol ◽  
Exome Sequence Data ◽  
Prediction Of Complications ◽  
Design And Methods

<p>Objective: Maturity-onset diabetes of the young (MODY) is frequently misdiagnosed as type 1 or type 2 diabetes. Correct diagnosis may result in a change in clinical treatment and impacts prediction of complications and familial risk. In this study, we aimed to assess the prevalence of MODY in multi-ethnic youth under age 20 years with a clinical diagnosis of type 2 diabetes.</p> <p> </p> <p>Research design and methods: We evaluated whole-exome sequence data of youth with a clinical diagnosis of type 2 diabetes. We considered participants to have MODY if they carried a MODY gene variant classified as likely pathogenic (LP) or pathogenic (P) according to current guidelines.</p> <p> </p> <p>Results: 93 of 3,333 participants (2.8%) carried an LP/P variant in <i>HNF4A </i>(16 participants)<i>, GCK </i>(23)<i>, HNF1A </i>(44), <i>PDX1</i> (5), <i>INS</i> (4), and <i>CEL</i> (1). Compared with those with no LP/P variants, youth with MODY had a younger age at diagnosis (12.9 ± 2.5 <i>vs</i> 13.6 ± 2.3 years, <i>P</i>=0.002) and lower fasting C-peptide levels (3.0 ± 1.7 <i>vs</i> 4.7 ± 3.5 ng/mL, <i>P</i><0.0001). Youth with MODY were less likely to have hypertension (6.9% <i>vs</i> 19.5%, <i>P</i>=0.007) and had higher HDL cholesterol (43.8 <i>vs</i> 39.7 mg/dL, <i>P=</i>0.006). </p> <p> </p> Conclusions: By comprehensively sequencing the coding regions of all MODY genes, we identified MODY in 2.8% of youth with clinically diagnosed type 2 diabetes; importantly, in 89% (n=83) the specific diagnosis would have changed clinical management. No clinical criterion reliably separated the two groups. New tools are needed to find ideal criteria to select individuals for genetic testing.

Higher HDL cholesterol to apolipoprotein A-I ratio is protective against the development of type 2 diabetes

2014 ◽  
Author(s):  
You-Cheol Hwang ◽  
In-Kyung Jeong ◽  
Kyu Jeung Ahn ◽  
Ho Yeon Chung ◽  
Cheol-Young Park
Keyword(s):  
Type 2 Diabetes ◽  
Hdl Cholesterol ◽  
Apolipoprotein A

1645-P: Polygenic Risk Score for Prediction of Complications in Men and Women with Type 2 Diabetes

Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 1645-P
Author(s):  
JOHANNE TREMBLAY ◽  
REDHA ATTAOUA ◽  
MOUNSIF HALOUI ◽  
RAMZAN TAHIR ◽  
CAROLE LONG ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Risk Score ◽  
Polygenic Risk Score ◽  
Men And Women ◽  
Polygenic Risk ◽  
Prediction Of Complications

Relative risk of cardiovascular disease is higher in women with type 2 diabetes, but not in those with prediabetes, as compared with men

2020 ◽  
Author(s):  
Elena Succurro ◽  
Teresa Vanessa Fiorentino ◽  
Sofia Miceli ◽  
Maria Perticone ◽  
Angela Sciacqua ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Longitudinal Study ◽  
Relative Risk ◽  
Hdl Cholesterol ◽  
Cross Sectional Study ◽  
Adverse Outcomes ◽  
Cross Sectional ◽  
Normal Glucose

<b>Objective</b>: Most, but not all studies suggested that women with type 2 diabetes have higher relative risk (RR) for cardiovascular disease (CVD) than men. More uncertainty exists on whether the RR for CVD is higher in prediabetic women compared to men. <p><b>Research Design and Methods</b>: In a cross-sectional study, in 3540 normal glucose tolerant (NGT), prediabetic, and diabetic adults, we compared the RR for prevalent non-fatal CVD between men and women. In a longitudinal study including 1658 NGT, prediabetic, and diabetic adults, we compared the RR for incident major adverse outcomes, including all-cause death, coronary heart disease, and cerebrovascular disease events after 5.6 years follow-up. </p> <p><b>Results:</b> Women with prediabetes and diabetes exhibited greater relative differences in BMI, waist circumference, blood pressure, total, LDL and HDL cholesterol, triglycerides, fasting glucose, hsCRP, and white blood cell count than men with prediabetes and diabetes when compared with their NGT counterparts. We found a higher RR for prevalent CVD in diabetic women (RR 9.29; 95% CI 4.73-18.25; <i>P</i><0.0001) than in men (RR 4.56; 95% CI 3.07-6.77; <i>P</i><0.0001), but no difference in RR for CVD was observed comparing prediabetic women and men. In the longitudinal study, we found that diabetic, but not prediabetic women have higher RR (RR 5.25; 95% CI 3.22-8.56; <i>P</i><0.0001) of incident major adverse outcomes than their male counterparts (RR 2.72; 95% CI 1.81-4.08; <i>P</i><0.0001).</p> <p><b>Conclusions:</b> This study suggests that diabetic, but not prediabetic, women have higher RR for prevalent and incident major adverse outcomes than men. </p>

scholarly journals Further improvement in glycemic control after switching from exenatide two times per day to exenatide once-weekly autoinjected suspension in patients with type 2 diabetes: 52-week results from the DURATION-NEO-1 study

2020 ◽  
Vol 8 (1) ◽  
pp. e000773
Author(s):  
Carol H Wysham ◽  
Julio Rosenstock ◽  
Marion L Vetter ◽  
Hui Wang ◽  
Elise Hardy ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Body Weight ◽  
Phase Iii ◽  
Open Label ◽  
Open Label Study ◽  
Registration Number ◽  
Efficacy Measures ◽  
Design And Methods ◽  
To Receive

IntroductionInvestigate the effects of switching from two times per day exenatide to once-weekly exenatide administered by autoinjector (exenatide once-weekly suspension by autoinjector (QWS-AI)) or treatment with exenatide QWS-AI for 1 year.Research design and methodsIn this phase III open-label study, adults with type 2 diabetes were randomized to receive exenatide QWS-AI (2 mg) or exenatide two times per day (5 mcg for 4 weeks, followed by 10 mcg) for 28 weeks. During a subsequent non-randomized 24-week extension, patients who received exenatide two times per day were switched to exenatide QWS-AI and those randomized to exenatide QWS-AI continued this treatment. Efficacy measures included changes from baseline in glycated hemoglobin (A1C), fasting plasma glucose (FPG), and body weight.ResultsIn total, 315 patients (mean baseline A1C of 8.5%) completed the initial 28 weeks of randomized treatment with exenatide QWS-AI (n=197) or exenatide two times per day (n=118) and were included in the 24-week extension (mean A1C of 7.0% and 7.3%, respectively, at week 28). From weeks 28–52, patients who switched from exenatide two times per day to exenatide QWS-AI had additional A1C reductions of approximately 0.5% (mean A1C change from baseline of –1.4% at week 52) and further reductions from baseline in FPG. Patients who continued exenatide QWS-AI treatment for 52 weeks showed clinically relevant A1C reductions (mean A1C change from baseline of –1.3% at week 52). Body-weight reductions achieved through week 28 were sustained at week 52 in both groups. There were no unexpected safety concerns or changes in the safety profile among patients who switched from exenatide two times per day to exenatide QWS-AI or those who continued exenatide QWS-AI treatment for 52 weeks.ConclusionsSwitching from exenatide two times per day to exenatide QWS-AI resulted in further A1C reductions and maintenance of earlier decreases in body weight, while continued therapy with exenatide QWS-AI for 52 weeks maintained A1C and body-weight reductions, without additional safety or tolerability concerns.Trial registration numberNCT01652716.

scholarly journals Increased stress, weight gain and less exercise in relation to glycemic control in people with type 1 and type 2 diabetes during the COVID-19 pandemic

2021 ◽  
Vol 9 (1) ◽  
pp. e002035
Author(s):  
Merel M Ruissen ◽  
Hannah Regeer ◽  
Cyril P Landstra ◽  
Marielle Schroijen ◽  
Ingrid Jazet ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Type 1 Diabetes ◽  
Weight Gain ◽  
Glycemic Control ◽  
Perceived Stress ◽  
Medical Center ◽  
Short Term ◽  
Design And Methods

IntroductionLockdown measures have a profound effect on many aspects of daily life relevant for diabetes self-management. We assessed whether lockdown measures, in the context of the COVID-19 pandemic, differentially affect perceived stress, body weight, exercise and related this to glycemic control in people with type 1 and type 2 diabetes.Research design and methodsWe performed a short-term observational cohort study at the Leiden University Medical Center. People with type 1 and type 2 diabetes ≥18 years were eligible to participate. Participants filled out online questionnaires, sent in blood for hemoglobin A1c (HbA1c) analysis and shared data of their flash or continuous glucose sensors. HbA1c during the lockdown was compared with the last known HbA1c before the lockdown.ResultsIn total, 435 people were included (type 1 diabetes n=280, type 2 diabetes n=155). An increase in perceived stress and anxiety, weight gain and less exercise was observed in both groups. There was improvement in glycemic control in the group with the highest HbA1c tertile (type 1 diabetes: −0.39% (−4.3 mmol/mol) (p<0.0001 and type 2 diabetes: −0.62% (−6.8 mmol/mol) (p=0.0036). Perceived stress was associated with difficulty with glycemic control (p<0.0001).ConclusionsAn increase in perceived stress and anxiety, weight gain and less exercise but no deterioration of glycemic control occurs in both people with relatively well-controlled type 1 and type 2 diabetes during short-term lockdown measures. As perceived stress showed to be associated with glycemic control, this provides opportunities for healthcare professionals to put more emphasis on psychological aspects during diabetes care consultations.

scholarly journals Plasma heat shock protein response to euglycemia in type 2 diabetes

2021 ◽  
Vol 9 (1) ◽  
pp. e002057
Author(s):  
Alexander S Atkin ◽  
Abu Saleh Md Moin ◽  
Ahmed Al-Qaissi ◽  
Thozhukat Sathyapalan ◽  
Stephen L Atkin ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Heat Shock ◽  
Protein Interactions ◽  
Glucose Variability ◽  
Interacting Protein ◽  
Ubiquitin Conjugating Enzyme ◽  
Shock Proteins ◽  
Protein Response ◽  
Design And Methods

IntroductionGlucose variability is associated with mortality and macrovascular diabetes complications. The mechanisms through which glucose variability mediates tissue damage are not well understood, although cellular oxidative stress is likely involved. As heat shock proteins (HSPs) play a role in the pathogenesis of type 2 diabetes (T2D) complications and are rapidly responsive, we hypothesized that HSP-related proteins (HSPRPs) would differ in diabetes and may respond to glucose normalization.Research design and methodsA prospective, parallel study in T2D (n=23) and controls (n=23) was undertaken. T2D subjects underwent insulin-induced blood glucose normalization from baseline 7.6±0.4 mmol/L (136.8±7.2 mg/dL) to 4.5±0.07 mmol/L (81±1.2 mg/dL) for 1 hour. Control subjects were maintained at 4.9±0.1 mmol/L (88.2±1.8 mg/dL). Slow Off-rate Modified Aptamer-scan plasma protein measurement determined a panel of HSPRPs.ResultsAt baseline, E3-ubiquitin-protein ligase (carboxyl-terminus of Hsc70 interacting protein (CHIP) or HSPABP2) was lower (p=0.03) and ubiquitin-conjugating enzyme E2G2 higher (p=0.003) in T2D versus controls. Following glucose normalization, DnaJ homolog subfamily B member 1 (DNAJB1 or HSP40) was reduced (p=0.02) in T2D, with HSP beta-1 (HSPB1) and HSP-70-1A (HSP70-1A) (p=0.07 and p=0.09, respectively) also approaching significance relative to T2D baseline levels.ConclusionsKey HSPRPs involved in critical protein interactions, CHIP and UBE2G2, were altered in diabetes at baseline. DNAJB1 fell in response to euglycemia, suggesting that HSPs are reacting to basal stress that could be mitigated by tight glucose control with reduction of glucose variability.

scholarly journals Antibodies Against the C-Terminus of ApoA-1 Are Inversely Associated with Cholesterol Efflux Capacity and HDL Metabolism in Subjects with and without Type 2 Diabetes Mellitus

2019 ◽  
Vol 20 (3) ◽  
pp. 732 ◽  
Author(s):  
Robin Dullaart ◽  
Sabrina Pagano ◽  
Frank Perton ◽  
Nicolas Vuilleumier
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Apolipoprotein B ◽  
Cholesterol Efflux ◽  
Hdl Cholesterol ◽  
Enzyme Linked Immunosorbent Assay ◽  
Cholesterol Efflux Capacity ◽  
C Terminus

Background: We determined relationships of cholesterol efflux capacity (CEC), plasma cholesterol esterification (EST) and cholesteryl ester transfer (CET) with anti-c-terminus apoA-1 (Ac-terAA1) and anti-apolipoprotein (apo)-1 (AAA1) autoantibodies in subjects with and without Type 2 diabetes mellitus (T2D). Methods: In 75 T2D subjects and 75 nondiabetic subjects, Ac-terAA1 and AAA1 plasma levels were measured by enzyme-linked immunosorbent assay. CEC was measured as [3H]-cholesterol efflux from human cultured fibroblasts to diluted individual subject plasma. Plasma EST and CET were assayed by isotope methods. Results: Ac-terAA1 and AAA1 levels and were similar between T2D and control subjects. Univariate regression analysis (n = 150) demonstrated that Ac-terAA1 levels were inversely correlated with CEC, EST, CET, total cholesterol, non-HDL cholesterol, triglycerides and apolipoprotein B, (p < 0.05 to p < 0.01), but not with glucose and HbA1c. In separate multivariable linear regression models, CEC, EST and CET were inversely associated with Ac-terAA1 levels independently of age, sex, T2D and drug use (β = −0.186, p = 0.026; β = −0.261, p < 0.001; and β = −0.321, p < 0.001; respectively). These associations were lost after additional adjustment for non-HDL cholesterol and triglycerides. No associations were observed for AAA1. Conclusions: CEC, plasma EST and CET are inversely associated with Ac-terAA1 autoantibodies, conceivably attributable to an inverse relationship of these autoantibodies with apolipoprotein B-containing lipoproteins.

scholarly journals Response to Comment on Sharif et al. HDL Cholesterol as a Residual Risk Factor for Vascular Events and All-Cause Mortality in Patients With Type 2 Diabetes. Diabetes Care 2016;39:1424–1430

Diabetes Care ◽  
2016 ◽  
Vol 39 (10) ◽  
pp. e190-e191
Author(s):  
Shahnam Sharif ◽  
Yolanda van der Graaf ◽  
Hendrik M. Nathoe ◽  
Harold W. de Valk ◽  
Frank L.J. Visseren ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Risk Factor ◽  
Diabetes Care ◽  
Hdl Cholesterol ◽  
Residual Risk ◽  
Vascular Events ◽  
All Cause Mortality

scholarly journals Anthropometry, Carbohydrate and Lipid Metabolism in the East Flanders Prospective Twin Survey: Linkage of Candidate Genes Using Two Sib-Pair Based Variance Components Analyses

2008 ◽  
Vol 11 (5) ◽  
pp. 505-516 ◽  
Author(s):  
Nicole Y. Souren ◽  
Maurice P. Zeegers ◽  
Rob G. J. H. Janssen ◽  
Anja Steyls ◽  
Marij Gielen ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Birth Weight ◽  
Variance Components ◽  
Single Point ◽  
Hdl Cholesterol ◽  
Suggestive Linkage ◽  
Phenotypic Data ◽  
Linkage Analyses ◽  
Cholesterol Levels

AbstractInsulin resistance and obesity are underlying causes of type 2 diabetes and therefore much interest is focused on the potential genes involved. A series of anthropometric and metabolic characteristic were measured in 240 MZ and 112 DZ twin pairs recruited from the East Flanders Prospective Twin Survey. Microsatellite markers located close to ABCC8, ADIPOQ, GCK, IGF1, IGFBP1, INSR, LEP, LEPR, PPARγ and the RETN gene were genotyped. Univariate single point variance components linkage analyses were performed using two methods: (1) the standard method, only comprising the phenotypic and genotypic data of the DZ twin pairs and (2) the extended method, also incorporating the phenotypic data of the MZ twin pairs. Suggestive linkages (LOD > 1) were observed between the ABCC8 marker and waist-to-hip ratio and HDL-cholesterol levels. Both markers flanking ADIPOQ showed suggestive linkage with triglycerides levels, the upstream marker also with body mass and HDL-cholesterol levels. The IGFBP1 marker showed suggestive linkage with fat mass, fasting insulin and leptin levels and the LEP marker showed suggestive linkage with birth weight. This study suggests that DNA variants in ABCC8, ADIPOQ, IGFBP1 and LEP gene region may predispose to type 2 diabetes. In addition, the two methods used to perform linkage analyses yielded similar results. This was however not the case for birth weight where chorionicity seems to be an important confounder.

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