Potential contribution of insecticide exposure and development of obesity and type 2 diabetes

The prevalence of Type 2 diabetes is rising rapidly in both developed and developing countries. Asia is developing as the epicentre of the escalating pandemic, reflecting rapid transitions in demography, migration, diet, and lifestyle patterns. The effective management of Type 2 diabetes in Asia may be complicated by differences in prevalence, risk factor profiles, genetic risk allele frequencies, and gene-environment interactions between different Asian countries, and between Asian and other continental populations. To reduce the worldwide burden of T2D, it will be important to understand the architecture of T2D susceptibility both within and between populations. This review will provide an overview of known genetic and nongenetic risk factors for T2D, placing the results from Asian studies in the context of broader global research. Given recent evidence from large-scale genetic studies of T2D, we place special emphasis on emerging knowledge about the genetic architecture of T2D and the potential contribution of genetic effects to population differences in risk.

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Reducing cardiovascular risk in patients with type 2 diabetes: the potential contribution of nicotinic acid

The British Journal of Diabetes ◽

10.1177/14746514050050060901 ◽

2005 ◽

Vol 5 (6) ◽

pp. 344-350 ◽

Cited By ~ 3

Author(s):

Luc F Van Gaal ◽

Frida Peiffer ◽

Dominique Ballaux

Keyword(s):

Type 2 Diabetes ◽

Cardiovascular Risk ◽

Nicotinic Acid ◽

Potential Contribution

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Potential contribution of metformin to the management of cardiovascular disease risk in patients with abdominal obesity, the metabolic syndrome and type 2 diabetes

Diabetes & Metabolism ◽

10.1016/s1262-3636(03)72788-8 ◽

2003 ◽

Vol 29 (4) ◽

pp. 6S53-6S61 ◽

Cited By ~ 18

Author(s):

J.P. Després

Keyword(s):

Type 2 Diabetes ◽

Cardiovascular Disease ◽

Metabolic Syndrome ◽

Abdominal Obesity ◽

Disease Risk ◽

Cardiovascular Disease Risk ◽

Potential Contribution ◽

The Metabolic Syndrome

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Assignment of Functional Relevance to Genes at Type 2 Diabetes-Associated Loci Through Investigation of β-Cell Mass Deficits

Molecular Endocrinology ◽

10.1210/me.2015-1243 ◽

2016 ◽

Vol 30 (4) ◽

pp. 429-445 ◽

Cited By ~ 9

Author(s):

Elizabeth A. O'Hare ◽

Laura M. Yerges-Armstrong ◽

James A. Perry ◽

Alan R. Shuldiner ◽

Norann A. Zaghloul

Keyword(s):

Type 2 Diabetes ◽

Candidate Genes ◽

Age Of Onset ◽

Cell Mass ◽

Transgenic Zebrafish ◽

Potential Contribution ◽

Β Cells ◽

Β Cell ◽

Multiple Genes

Type 2 diabetes (T2D) has been associated with a large number of genomic loci, many of which encompass multiple genes without a definitive causal gene. This complexity has hindered efforts to clearly identify functional candidate genes and interpret their role in mediating susceptibility to disease. Here we examined the relevance of individual genes found at T2D-associated loci by assessing their potential contribution to a phenotype relevant to the disease state: production and maintenance of β-cell mass. Using transgenic zebrafish in which β-cell mass could be rapidly visualized in vivo, we systematically suppressed the expression of orthologs of genes found at T2D-associated genomic loci. Overall, we tested 67 orthologs, many of which had no known relevance to β-cell mass, at 62 human T2D-associated loci, including eight loci with multiple candidate genes. In total we identified 25 genes that were necessary for proper β-cell mass, providing functional evidence for their role in a physiological phenotype directly related to T2D. Of these, 16 had not previously been implicated in the regulation of β-cell mass. Strikingly, we identified single functional candidate genes at the majority of the loci for which multiple genes were analyzed. Further investigation into the contribution of the 25 genes to the adaptive capacity of β-cells suggested that the majority of genes were not required for glucose-induced expansion of β-cell mass but were significantly necessary for the regeneration of β-cells. These findings suggest that genetically programmed deficiencies in β-cell mass may be related to impaired maintenance. Finally, we investigated the relevance of our findings to human T2D onset in diabetic individuals from the Old Order Amish and found that risk alleles in β-cell mass genes were associated with significantly younger age of onset and lower body mass index. Taken together, our study offers a functional approach to assign relevance to genes at T2D-associated loci and offers experimental evidence for the defining role of β-cell mass maintenance in genetic susceptibility to T2D onset.

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Association of puberty timing with Type 2 diabetes: Systematic review and meta-analysis

10.1101/19000521 ◽

2019 ◽

Author(s):

Tuck Seng Cheng ◽

Felix R. Day ◽

Rajalakshmi Lakshman ◽

Ken K. Ong

Keyword(s):

Type 2 Diabetes ◽

Meta Analysis ◽

Population Attributable Risk ◽

Age At Menarche ◽

Potential Contribution ◽

Early Menarche ◽

Published Evidence ◽

Design And Methods ◽

Sexual Characteristic

OBJECTIVEWe aimed to systematically review published evidence on the association between puberty timing and Type 2 diabetes or impaired glucose tolerance (T2D/IGT), with and without adjustment for adiposity, and to estimate its potential contribution to the burden of T2D.RESEARCH DESIGN AND METHODSWe searched PubMed, Medline and Embase databases for publications until February 2019 on the timing of any secondary sexual characteristic in boys or girls in relation to T2D/IGT. Inverse-weighted random-effects meta-analysis was used to pool reported estimates and meta-regression to explore sources of heterogeneity.RESULTSTwenty eight observational studies were identified. All assessed age at menarche (AAM) in women (combined N=1,228,306); only one study additionally included men. In models without adjustment for adult adiposity, T2D/IGT risk was higher per year earlier AAM (relative risk (RR)=0.91, 95% confidence interval (CI)=0.89-0.93, 11 estimates, n=833,529, I2=85.4%) and for early versus later menarche (RR=1.41, 95% CI=1.28-1.55, 23 estimates, n=1,185,444, I2=87.8%). Associations were weaker but still evident in models adjusted for adiposity (AAM: RR=0.97 per year, 95% CI=0.95-0.98, 12 estimates, n=852,268, I2=51.8%; early menarche: RR=1.19, 95% CI=1.11-1.28, 21 estimates, n=890,583, I2=68.1%). Associations were stronger among Caucasians than Asians, and in populations with earlier average AAM. The estimated population attributable risk of T2D in UK Caucasians due to early menarche, unadjusted and adjusted for adiposity, was 12.6% (95% CI=11.0-14.3) and 5.1% (95% CI=3.6-6.7), respectively.CONCLUSIONSA substantial proportion of T2D in women is attributable to early menarche timing. This will increase in light of global secular trends towards earlier puberty timing.

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Euglycemic Ketoacidosis in a Patient with Metastatic Non-Small-Cell Lung Adenocarcinoma and Concomitant Pulmonary Embolism

Case Reports in Endocrinology ◽

10.1155/2020/8882299 ◽

2020 ◽

Vol 2020 ◽

pp. 1-3 ◽

Cited By ~ 1

Author(s):

Robert Sean O’Neill ◽

Lauren Tyack ◽

Mary Freeman ◽

Hussein Soudy Hussein

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Pulmonary Embolism ◽

Type 2 Diabetes Mellitus ◽

Lung Adenocarcinoma ◽

Single Agent ◽

Potential Contribution ◽

Arterial Blood Gas ◽

Arterial Blood

Euglycemic ketoacidosis is a recognised side effect secondary to sodium-glucose cotransporter 2 inhibitor use in the treatment of type 2 diabetes mellitus; however, there is scarce evidence to suggest whether preexisting comorbid conditions contribute to the development of this potentially life-threatening complication. We describe a case of euglycemic ketoacidosis in a patient with type 2 diabetes mellitus in the context of empagliflozin use after a recent diagnosis of metastatic lung adenocarcinoma. The diagnosis was complicated by a pulmonary embolism and hospital-acquired pneumonia, and was subsequently established after an anion-gap metabolic acidosis was identified on arterial blood gas and serum ketone measurement. The patient required admission to the intensive care unit for fluid resuscitation and regular intravenous insulin to ensure resolution of acidosis and maintenance of normoglycaemia. The patient was discharged to home for outpatient single-agent pembrolizumab for treatment of his lung adenocarcinoma. This article highlights the importance or awareness of oral hypoglycaemic medications and their side effects, along with providing further evidence for the potential contribution of malignancy to the development of euglycemic ketoacidosis in a patient with type 2 diabetes mellitus.

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