The SLC16A11 risk haplotype is associated with decreased insulin action, higher transaminases and large-size adipocytes

Objective A haplotype at chromosome 17p13 that reduces expression and function of the solute carrier transporter SLC16A11 is associated with increased risk for type 2 diabetes in Mexicans. We aim to investigate the detailed metabolic profile of SLC16A11 risk haplotype carriers to identify potential physiological mechanisms explaining the increased type 2 diabetes risk. Design Cross-sectional study. Methods We evaluated carriers (n = 72) and non-carriers (n = 75) of the SLC16A11 risk haplotype, with or without type 2 diabetes. An independent sample of 1069 subjects was used to replicate biochemical findings. The evaluation included euglycemic–hyperinsulinemic clamp, frequently sampled intravenous glucose tolerance test (FSIVGTT), dual-energy X-ray absorptiometry (DXA), MRI and spectroscopy and subcutaneous abdominal adipose tissue biopsies. Results Fat-free mass (FFM)-adjusted M value was lower in carriers of the SLC16A11 risk haplotype after adjusting for age and type 2 diabetes status (β = −0.164, P = 0.04). Subjects with type 2 diabetes and the risk haplotype demonstrated an increase of 8.76 U/L in alanine aminotransferase (ALT) (P = 0.02) and of 7.34 U/L in gamma-glutamyltransferase (GGT) (P = 0.05) compared with non-carriers and after adjusting for gender, age and ancestry. Among women with the risk haplotype and normal BMI, the adipocyte size was higher (P < 0.001). Conclusions Individuals carrying the SLC16A11 risk haplotype exhibited decreased insulin action. Higher serum ALT and GGT levels were found in carriers with type 2 diabetes, and larger adipocytes in subcutaneous fat in the size distribution in carrier women with normal weight.

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HLA Class II Allele Analyses Implicate Common Genetic Components in Type 1 and Non–Insulin-Treated Type 2 Diabetes

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgaa027 ◽

2020 ◽

Vol 105 (3) ◽

pp. e245-e254 ◽

Cited By ~ 1

Author(s):

Thomas Jacobi ◽

Lucas Massier ◽

Nora Klöting ◽

Katrin Horn ◽

Alexander Schuch ◽

...

Keyword(s):

Type 2 Diabetes ◽

Type 1 Diabetes ◽

Class Ii ◽

Hla Class Ii ◽

Risk Haplotype ◽

Genetic Components ◽

Hla Genotypes ◽

Increased Risk

Abstract Context Common genetic susceptibility may underlie the frequently observed co-occurrence of type 1 and type 2 diabetes in families. Given the role of HLA class II genes in the pathophysiology of type 1 diabetes, the aim of the present study was to test the association of high density imputed human leukocyte antigen (HLA) genotypes with type 2 diabetes. Objectives and Design Three cohorts (Ntotal = 10 413) from Leipzig, Germany were included in this study: LIFE-Adult (N = 4649), LIFE-Heart (N = 4815) and the Sorbs (N = 949) cohort. Detailed metabolic phenotyping and genome-wide single nucleotide polymorphism (SNP) data were available for all subjects. Using 1000 Genome imputation data, HLA genotypes were imputed on 4-digit level and association tests for type 2 diabetes, and related metabolic traits were conducted. Results In a meta-analysis including all 3 cohorts, the absence of HLA-DRB5 was associated with increased risk of type 2 diabetes (P = 0.001). In contrast, HLA-DQB*06:02 and HLA-DQA*01:02 had a protective effect on type 2 diabetes (P = 0.005 and 0.003, respectively). Both alleles are part of the well-established type 1 diabetes protective haplotype DRB1*15:01~DQA1*01:02~DQB1*06:02, which was also associated with reduced risk of type 2 diabetes (OR 0.84; P = 0.005). On the contrary, the DRB1*07:01~DQA1*02:01~DQB1*03:03 was identified as a risk haplotype in non–insulin-treated diabetes (OR 1.37; P = 0.002). Conclusions Genetic variation in the HLA class II locus exerts risk and protective effects on non–insulin-treated type 2 diabetes. Our data suggest that the genetic architecture of type 1 diabetes and type 2 diabetes might share common components on the HLA class II locus.

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The Relationship between Macronutrient Distribution and Type 2 Diabetes in Asian Indians

Nutrients ◽

10.3390/nu13124406 ◽

2021 ◽

Vol 13 (12) ◽

pp. 4406

Author(s):

Amisha Pandya ◽

Mira Mehta ◽

Kavitha Sankavaram

Keyword(s):

Type 2 Diabetes ◽

Asian Indians ◽

Diabetes Management ◽

Critical Role ◽

Convenience Sample ◽

Specific Distribution ◽

Diabetes Status ◽

Increased Risk ◽

Macronutrient Distribution

Asian Indians (AIs) are at increased risk for type 2 diabetes mellitus than other ethnic groups. AIs also have lower body mass index (BMI) values than other populations, so can benefit from strategies other than weight reduction. Macronutrient distributions are associated with improved glycemic control; however, no specific distribution is generally recommended. This study looks at whether a macronutrient distribution of 50:30:20 (percent of total calories from carbohydrates, fats, and protein) is related to diabetes status in AIs. Diet and Hemoglobin A1c (HbA1c) were assessed from convenience sample of AI adults in Maryland. A ratio of actual to needed calories using the 50:30:20 macronutrient distribution was then tested against diabetes status to identify associations. All groups except non-diabetic females, were in negative energy balance. The non-diabetic group consumed larger actual to needed ratios of protein than pre-diabetics and diabetics. However, all groups consumed protein at the lower end of the Acceptable Macronutrient Distribution Range (AMDR), and the quality of all macronutrients consumed was low. Therefore, weight loss may not be the recommendation for diabetes management for AIs. Increasing protein and insoluble fiber consumption, could play a critical role.

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Impact of undiagnosed type 2 diabetes and pre-diabetes on severity and mortality for SARS-CoV-2 infection

BMJ Open Diabetes Research & Care ◽

10.1136/bmjdrc-2020-002026 ◽

2021 ◽

Vol 9 (1) ◽

pp. e002026

Author(s):

Arsenio Vargas-Vázquez ◽

Omar Yaxmehen Bello-Chavolla ◽

Edgar Ortiz-Brizuela ◽

Alejandro Campos-Muñoz ◽

Roopa Mehta ◽

...

Keyword(s):

Risk Factors ◽

Type 2 Diabetes ◽

De Novo ◽

Glycosylated Hemoglobin ◽

Undiagnosed Diabetes ◽

Individual Risk ◽

Diabetes Status ◽

Increased Risk ◽

The Impact

IntroductionDiabetes and hyperglycemia are risk factors for critical COVID-19 outcomes; however, the impact of pre-diabetes and previously unidentified cases of diabetes remains undefined. Here, we profiled hospitalized patients with undiagnosed type 2 diabetes and pre-diabetes to evaluate its impact on adverse COVID-19 outcomes. We also explored the role of de novo and intrahospital hyperglycemia in mediating critical COVID-19 outcomes.Research design and methodsProspective cohort of 317 hospitalized COVID-19 cases from a Mexico City reference center. Type 2 diabetes was defined as previous diagnosis or treatment with diabetes medication, undiagnosed diabetes and pre-diabetes using glycosylated hemoglobin (HbA1c) American Diabetes Association (ADA) criteria and de novo or intrahospital hyperglycemia as fasting plasma glucose (FPG) ≥140 mg/dL. Logistic and Cox proportional regression models were used to model risk for COVID-19 outcomes.ResultsOverall, 159 cases (50.2%) had type 2 diabetes and 125 had pre-diabetes (39.4%), while 31.4% of patients with type 2 diabetes were previously undiagnosed. Among 20.0% of pre-diabetes cases and 6.1% of normal-range HbA1c had de novo hyperglycemia. FPG was the better predictor for critical COVID-19 compared with HbA1c. Undiagnosed type 2 diabetes (OR: 5.76, 95% CI 1.46 to 27.11) and pre-diabetes (OR: 4.15, 95% CI 1.29 to 16.75) conferred increased risk of severe COVID-19. De novo/intrahospital hyperglycemia predicted critical COVID-19 outcomes independent of diabetes status.ConclusionsUndiagnosed type 2 diabetes, pre-diabetes and de novo hyperglycemia are risk factors for critical COVID-19. HbA1c must be measured early to adequately assess individual risk considering the large rates of undiagnosed type 2 diabetes in Mexico.

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METS-IR, a novel score to evaluate insulin sensitivity, is predictive of visceral adiposity and incident type 2 diabetes

Acta Endocrinologica ◽

10.1530/eje-17-0883 ◽

2018 ◽

Vol 178 (5) ◽

pp. 533-544 ◽

Cited By ~ 16

Author(s):

Omar Yaxmehen Bello-Chavolla ◽

Paloma Almeda-Valdes ◽

Donaji Gomez-Velasco ◽

Tannia Viveros-Ruiz ◽

Ivette Cruz-Bautista ◽

...

Keyword(s):

Type 2 Diabetes ◽

Insulin Sensitivity ◽

Diagnostic Performance ◽

Fat Free Mass ◽

Resonance Spectroscopy ◽

Intravenous Glucose ◽

Incident Type ◽

Adjusted Risk ◽

Incident Type 2 Diabetes

Objective We developed a novel non-insulin-based fasting score to evaluate insulin sensitivity validated against the euglycemic–hyperinsulinemic clamp (EHC). We also evaluated its correlation with ectopic fact accumulation and its capacity to predict incident type 2 diabetes mellitus (T2D). Design and methods The discovery sample was composed by 125 subjects (57 without and 68 with T2D) that underwent an EHC. We defined METS-IR as Ln((2*G0)+TG0)*BMI)/(Ln(HDL-c)) (G0: fasting glucose, TG0: fasting triglycerides, BMI: body mass index, HDL-c: high-density lipoprotein cholesterol), and compared its diagnostic performance against the M-value adjusted by fat-free mass (MFFM) obtained by an EHC. METS-IR was validated in a sample with EHC data, a sample with modified frequently sampled intravenous glucose tolerance test (FSIVGTT) data and a large cohort against HOMA-IR. We evaluated the correlation of the score with intrahepatic and intrapancreatic fat measured using magnetic resonance spectroscopy. Subsequently, we evaluated its ability to predict incident T2D cases in a prospective validation cohort of 6144 subjects. Results METS-IR demonstrated the better correlation with the MFFM (ρ = −0.622, P < 0.001) and diagnostic performance to detect impaired insulin sensitivity compared to both EHC (AUC: 0.84, 95% CI: 0.78–0.90) and the SI index obtained from the FSIVGTT (AUC: 0.67, 95% CI: 0.53–0.81). METS-IR significantly correlated with intravisceral, intrahepatic and intrapancreatic fat and fasting insulin levels (P < 0.001). After a two-year follow-up, subjects with METS-IR in the highest quartile (>50.39) had the highest adjusted risk to develop T2D (HR: 3.91, 95% CI: 2.25–6.81). Furthermore, subjects with incident T2D had higher baseline METS-IR compared to healthy controls (50.2 ± 10.2 vs 44.7 ± 9.2, P < 0.001). Conclusion METS-IR is a novel score to evaluate cardiometabolic risk in healthy and at-risk subjects and a promising tool for screening of insulin sensitivity.

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Stuttering and Incident Type 2 Diabetes: A Population-Based Study of 2.2 Million Adolescents

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgaa988 ◽

2021 ◽

Author(s):

Avishai M Tsur ◽

Shir Hershkovich ◽

Inbar Zucker ◽

Miri Lutski ◽

Orit Pinhas-Hamiel ◽

...

Keyword(s):

Type 2 Diabetes ◽

Military Service ◽

Reference Group ◽

Population Based ◽

Population Based Study ◽

Incident Type ◽

Diabetes Status ◽

Increased Risk ◽

Incident Type 2 Diabetes

Abstract Purpose To investigate the association between stuttering in adolescence and incident type 2 diabetes in young adulthood. Methods This nationwide population-based study included 2 193 855 adolescents of age 16 to 20 years who were assessed for military service between 1980 and 2013. Diagnoses of stuttering in adolescence were confirmed by a speech-language pathologist. Diabetes status for each individual as of December 31, 2016, was determined by linkage to the Israeli National Diabetes Registry. Relationships were analyzed using regression models adjusted for socioeconomic variables, cognitive performance, coexisting morbidities, and adolescent body mass index. Results Analysis was stratified by sex (Pinteraction = 0.035). Of the 4443 (0.4%) adolescent men with stuttering, 162 (3.7%) developed type 2 diabetes, compared with 25 678 (2.1%) men without stuttering (adjusted odds ratio [OR] 1.3; 95% CI, 1.1-1.6). This relationship persisted when unaffected brothers of men with stuttering were used as the reference group (adjusted OR = 1.5; 95% CI, 1.01-2.2), or when the analysis included only adolescents with unimpaired health at baseline (adjusted OR = 1.4; 95% CI, 1.1-1.7). The association was stronger in later birth cohorts, with an adjusted OR of 2.4 (1.4-4.1) for cases of type 2 diabetes before age 40. Of the 503 (0.1%) adolescent women with stuttering 7 (1.4%) developed type 2 diabetes, compared with 10 139 (1.1%) women without stuttering (OR = 2.03; 95% CI, 0.48-2.20). Conclusions Adolescent stuttering is associated with an increased risk for early-onset type 2 diabetes among men.

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ERECTILE DYSFUNCTION IN MEN WITH TYPE 2 DIABETES: IS IT ASSOCIATED WITH POOR GLYCEMIC CONTROL?

Journal of Men s Health ◽

10.22374/jomh.v15i1.104 ◽

2019 ◽

Vol 15 (1) ◽

pp. e12-e22

Author(s):

Turky H Almigbal

Keyword(s):

Type 2 Diabetes ◽

Erectile Dysfunction ◽

Glycemic Control ◽

Poor Glycemic Control ◽

P Value ◽

Clinical Issue ◽

Duration Of Diabetes ◽

Diabetes Status ◽

Increased Risk

Background and Objective Erectile dysfunction (ED) is a widespread clinical issue with many new cases diagnosed every year. The prevalence of ED in men with type 2 diabetes millitus (T2DM) ranges from 35–90%, depending on patient characteristics and the method used to diagnose it. There is inconsistent evidence about the association between ED and the degree of glycemic control in men with T2DM. Our main objective was to investigate the association between ED in patients with T2DM and poor glycemic control, as well as other factors. Material and Methods This is a cross-sectional study based on a self-administrated questionnaire. The study was conducted from July to September 2017at King Saud University-Medical City, Riyadh, Saudi Arabia. Participants in this study were older than 18-years-old. The data from the questionnaire were analyzed using the SPSS program (Armonk, NY, USA). Results The prevalence of ED is 80.5%, while a severe degree is seen at 33%. There were several factors significantly associated with it, including age (p-value = 0.01), education level (p-value = 0.01), monthly income (p-value = 0.01), occupation status (p-value = 0.01), duration of diabetes (p -value = 0.01), type of treatment of diabetes ( p -value = 0.01), and diabetes status (p -value = 0.01). Increasing age (above 60 years of age), duration, and uncontrolled diabetes were associated with a high risk of developing ED. Conclusion ED was highly prevalent in patients with T2DM and poor glycemic control, as well as advanced age and duration of diabetes: each was associated with increased risk of ED.

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