Linkage of Type 2 Diabetes Mellitus and of Age at Onset to a Genetic Location on Chromosome 10q in Mexican Americans

Purpose Type 2 diabetes mellitus (T2DM) is an urgent public health problem and disproportionately affects Mexican Americans. The gut microbiome contributes to the pathophysiology of diabetes; however, no studies have examined this association in Mexican-Americans. The objective of this study was to compare gut microbiome composition between Mexican-Americans with and without T2DM. Methods This was a cross-sectional study of volunteers from San Antonio, TX. Subjects were 18 years or older and self-identified as Mexican American. Subjects were grouped by prior T2DM diagnosis. Eligible subjects attended a clinic visit to provide demographic and medical information. Thereafter, subjects recorded their dietary intake for three days and collected a stool sample on the fourth day. Stool 16s rRNA sequences were classified into operational taxonomic units (OTUs) via the mothur bayesian classifier and referenced to the Greengenes database. Shannon diversity and bacterial taxa relative abundance were compared between groups using the Wilcoxon rank sum test. Beta diversity was estimated using Bray-Curtis indices and compared between groups using PERMANOVA. Results Thirty-seven subjects were included, 14 (38%) with diabetes and 23 (62%) without diabetes. Groups were well-matched by body mass index and comorbid conditions. Shannon diversity was not significantly different between those with and without T2DM (3.26 vs. 3.31; p = 0.341). Beta diversity was not significantly associated with T2DM diagnosis (p = 0.201). The relative abundance of the most common bacterial phyla and families did not significantly differ between groups; however, 16 OTUs were significantly different between groups. Conclusions Although alpha diversity was not significantly different between diabetic and non-diabetic Mexican Americans, the abundance of certain bacterial taxa were significantly different between groups.

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Prevalence of diabetic retinopathy in type 2 diabetes mellitus patients attending medicine out-patient department of a tertiary care hospital in Alappuzha, Kerala, India

International Journal of Research in Medical Sciences ◽

10.18203/2320-6012.ijrms20171259 ◽

2017 ◽

Vol 5 (4) ◽

pp. 1532 ◽

Cited By ~ 1

Author(s):

Koushiki Mani ◽

Rose Davy C.

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Diabetic Retinopathy ◽

Age At Onset ◽

Proliferative Retinopathy ◽

Duration Of Diabetes ◽

Onset Of Diabetes ◽

Patient Department

Background: Diabetic retinopathy is a microvascular complication affecting the eyes of both Type 1 and Type 2 diabetes mellitus due to long-term hyperglycaemia. Diabetic retinopathy is the leading cause of blindness among working aged adults around the world. There are various factors leading to the development of diabetic retinopathy namely duration of diabetes, glycaemic control, age at onset of diabetes, uncontrolled hypertension. This is a hospital based cross-sectional study which aimed to study the prevalence of diabetic retinopathy in type 2 diabetes mellitus patients attending Medicine out-patient department of Government T. D. Medical College, Alappuzha, Kerala, India. The factors contributing to the development of retinopathy was also studied.Methods: 200 already diagnosed type 2 diabetic subjects were included in the study. Subjects were explained about the study and once the consent was received, data regarding age, gender, age at onset of diabetes, duration of diabetes, history of smoking, alcohol intake, and socio-economic status was documented. Height and weight was measured. Blood pressure was recorded with mercury sphygmomanometer. Then the subjects were evaluated for diabetic retinopathy by fundus examination after dilating the eyes. Findings were noted and subjects were categorized as no retinopathy, nonproliferative and proliferative diabetic retinopathy using the ETDRS classification.Results: In present study, out of 200 subjects, 63 subjects (31.5%) were affected with diabetic retinopathy (non-proliferative retinopathy=22.5%, proliferative retinopathy=9%). Prevalence of mild, moderate and severe non-proliferative retinopathy was 7.5% each. Significant association was found between diabetic retinopathy and duration of diabetes.Conclusions: Therefore, periodic screening of diabetic patients should be carried out for early detection and prevention of loss of vision.

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An Insertion/Deletion Polymorphism in the alpha2B Adrenoceptor Gene is Associated with Age at Onset of Type 2 Diabetes Mellitus

Experimental and Clinical Endocrinology & Diabetes ◽

10.1055/s-2006-924330 ◽

2006 ◽

Vol 114 (08) ◽

pp. 424-427 ◽

Cited By ~ 5

Author(s):

D. Papazoglou ◽

N. Papanas ◽

K. Papatheodorou ◽

S. Kotsiou ◽

D. Christakidis ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Age At Onset ◽

Deletion Polymorphism

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Evaluation of gremlin 1 (GREM1) as a candidate susceptibility gene for albuminuria-related traits in Mexican Americans with type 2 diabetes mellitus

Metabolism ◽

10.1016/j.metabol.2009.04.039 ◽

2009 ◽

Vol 58 (10) ◽

pp. 1496-1502 ◽

Cited By ~ 6

Author(s):

Farook Thameem ◽

Sobha Puppala ◽

Xin He ◽

Nedal H. Arar ◽

Michael P. Stern ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Mexican Americans ◽

Susceptibility Gene ◽

Gremlin 1

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Predicting the efficacy of exenatide in Parkinson’s disease using genetics – a Mendelian randomization study

10.1101/2020.10.20.20215855 ◽

2020 ◽

Author(s):

Catherine S. Storm ◽

Demis A. Kia ◽

Mona Almramhi ◽

Dilan Athauda ◽

Stephen Burgess ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Parkinson’S Disease ◽

Parkinson's Disease ◽

Type 2 Diabetes Mellitus ◽

Brain Tissue ◽

Mendelian Randomization ◽

Disease Risk ◽

Age At Onset

AbstractBackgroundExenatide is a glucagon-like peptide 1 receptor (GLP1R) agonist used in type 2 diabetes mellitus that has shown promise for Parkinson’s disease in a phase II clinical trial. Drugs with genetic evidence are more likely to be successful in clinical trials. In this study we investigated whether the genetic technique Mendelian randomization (MR) can “rediscover” the effects of exenatide on diabetes and weight, and predict its efficacy for Parkinson’s disease.MethodsWe used genetic variants associated with increased expression of GLP1R in blood to proxy exenatide, as well as variants associated with expression of DPP4, TLR4 and 15 genes thought to act downstream of GLP1R or mimicking alternative actions of GLP-1 in blood and brain tissue. Using an MR approach, we predict the effect of exenatide on type 2 diabetes risk, body mass index (BMI), Parkinson’s disease risk and several Parkinson’s disease progression markers.ResultsWe found that genetically-raised GLP1R expression in blood was associated with lower BMI and possibly type 2 diabetes mellitus risk, but not Parkinson’s disease risk, age at onset or progression. Reduced DPP4 expression in brain tissue was significantly associated with increased Parkinson’s disease risk.ConclusionsWe demonstrate the usefulness of MR using expression data in predicting the efficacy of a drug and exploring its mechanism of action. Our data suggest that GLP-1 mimetics like exenatide, if ultimately proven to be effective in Parkinson’s disease, will be through a mechanism that is independent of GLP1R in blood.

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A study to assess clinical profile of Indian type 2 diabetes mellitus patients treated with Teneligliptin-ASPIRE study

International Journal of Basic & Clinical Pharmacology ◽

10.18203/2319-2003.ijbcp20192648 ◽

2019 ◽

Vol 8 (7) ◽

pp. 1542

Author(s):

Manoj Chadha ◽

Rajnish Dhediya ◽

Gaurav Saxena ◽

Swati Lad Naik

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Age At Onset ◽

Clinical Profile ◽

Postprandial Blood Glucose ◽

Newly Diagnosed ◽

Real World Data ◽

Patient Profile

Background: Teneligliptin is a DPP-4 inhibitor with unique chemical structure. Efficacy and safety of Teneligliptin is well established in the patients with type 2 diabetes mellitus (T2DM) in different randomized controlled trials. However, limited real-world data is available for Teneligliptin pertaining to Indian T2DM patient profile such as demographics, duration of disease, currently prescribed anti-hyperglycemic drugs, initiation of Teneligliptin as monotherapy or as an add on therapy.Methods: A cross-sectional, multicenter, non-interventional study was conducted to understand the demographics and clinical profile of Indian T2DM patients (n=5091) who were prescribed Teneligliptin.Results: Majority of patients were male (65.2%) with family history of T2DM present in 43.45% of cases. Age at onset of T2DM was 51.1±11.6 years. Among the T2DM patients, 36.2% of patients were newly diagnosed and more than half of them (54.7%) were uncontrolled with current anti-hyperglycemic drugs. Mean HbA1c level among these patients was 8.09±1.3%. Mean fasting and postprandial blood glucose levels were 170.2±46.9 mg/dl and 255.3±69.3 mg/dl respectively. Teneligliptin was prescribed as monotherapy in 2165 (41.66 %) of patients while as dual, triple and quadruple therapy in 2346 (46.08%) and 551 (10.82%) and 29 (0.56%) respectively. Among the patients on current anti-hyperglycemic treatment, most commonly prescribed drugs along with Teneligliptin were metformin (43.39%) followed by glimepiride (11%) and voglibose (3.42%).Conclusions: Teneligliptin is preferred as monotherapy and combination with metformin and sulfonylureas (mostly glimepiride) in newly diagnosed and uncontrolled T2DM patients in Indian scenario.

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Molecular scanning for mutations in the insulin receptor substrate-1 (IRS-1) gene in Mexican Americans with Type 2 diabetes mellitus

Diabetes/Metabolism Research and Reviews ◽

10.1002/1520-7560(2000)9999:9999<::aid-dmrr129>3.0.co;2-b ◽

2000 ◽

Vol 16 (5) ◽

pp. 370-377 ◽

Cited By ~ 23

Author(s):

Francesco S. Celi ◽

Carlo Negri ◽

Keith Tanner ◽

Nina Raben ◽

Flora De Pablo ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Insulin Receptor ◽

Mexican Americans ◽

Insulin Receptor Substrate ◽

Insulin Receptor Substrate 1

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Homozygous combination of calpain 10 gene haplotypes is associated with type 2 diabetes mellitus in a Polish population

Acta Endocrinologica ◽

10.1530/eje.0.1460695 ◽

2002 ◽

pp. 695-699 ◽

Cited By ~ 50

Author(s):

MT Malecki ◽

DK Moczulski ◽

T Klupa ◽

K Wanic ◽

K Cyganek ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Mexican Americans ◽

Polish Population ◽

Haplotype Combination ◽

Increased Risk ◽

Calpain 10

OBJECTIVE: The polymorphisms of two genes have recently been associated with complex forms of type 2 diabetes mellitus (T2DM): calpain 10 and peroxisome proliferator-activated receptor-gamma (PPARgamma). Calpain 10 is a member of a large family of intracellular proteases. It was shown in Mexican-Americans and other populations that variants of three single nucleotide polymorphisms (SNPs), -43, -19, and -63, of this ubiquitously expressed protein influence susceptibility to T2DM. However, substantial differences were shown between ethnic groups in at risk alleles and haplotypes as well as in their attributable risk. Thus, it is important to determine the role of calpain 10 in various populations. AIM: To examine the role of calpain 10 SNPs -43, -19, and -63 in genetic susceptibility to T2DM in a Polish population. METHODS: Overall, 377 individuals were examined: 229 T2DM patients and 148 control individuals. The groups were genotyped for calpain 10 SNP-43, SNP-19, and SNP-63. SNP-19 was examined by electrophoresis of the PCR product on agarose gel by size, while the restriction fragment length polymorphism (RFLP) method was used for the two other markers. Differences in allele, genotype, haplotype, and haplotype combination distribution between the groups were examined by chi(2) test. RESULTS: Distributions of alleles, genotypes, and haplotypes at three loci defined by examined SNPs were not significantly different between the groups. However, the homozygote combination of 121 haplotype was more prevalent in the T2DM group than in the controls (17.9% vs 10.1%, P=0.039). No difference was observed in the 112/121 haplotype distribution. This heterozygous haplotype combination was associated with increased risk of T2DM in several populations. CONCLUSION: The results of our study suggest the association of calpain 10 121/121 haplotype combination created by SNPs -43, -19, and -63 with T2DM in a Polish population. However, we were not able to confirm the previously described role of the heterozygous 112/121 haplotype combination in susceptibility to T2DM.

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