A causal synthesis and models

2019 ◽  
pp. 198-220
Author(s):  
Raj S. Bhopal
Keyword(s):  
South Asians ◽  
Dietary Factors ◽  
Vasa Vasorum ◽  
Beta Cell Dysfunction ◽  
Ectopic Fat ◽  
Cell Dysfunction ◽  
High Prevalence ◽  
Liver And Pancreas ◽  
High Glucose Level ◽  
The Brain

This chapter synthesizes explanations that are relevant to each of diabetes, CHD, and stroke, and all three collectively. This synthesis emphasizes glycation of tissues, possibly leading to arterial stiffness and microcirculatory damage. In addition to endothelial pathways to atherosclerosis an external (adventitial) one is proposed, i.e. microcirculatory damage to the vasa vasorum, the network of arterioles that supplies nutrients to the larger arteries themselves. DM2 plays into this pathway through glycosylation and dyslipidaemia. The cause of the high prevalence of DM2 in South Asians may lie in protective factors in Europeans not just detrimental ones in South Asians. The high glucose level is considered as an allostatic mechanism controlled by the brain. In addition to the ectopic fat in their liver and pancreas as the cause of beta cell dysfunction, two additional ideas are proposed, i.e. firstly, microcirculatory damage and secondly, glycation, possibly compounded by dietary factors including neoformed contaminants, e.g. AGEs.

Epidemic of Cardiovascular Disease and Diabetes

2019 ◽  
Author(s):  
Raj S. Bhopal
Keyword(s):  
Cardiovascular Disease ◽  
Scientific Literature ◽  
Low Cost ◽  
South Asians ◽  
Cost Effective ◽  
Causal Explanations ◽  
Cell Dysfunction ◽  
Liver And Pancreas ◽  
Health And Disease

Coronary heart disease (CHD) and stroke, collectively cardiovascular disease (CVD), are caused by narrowing and blockage of the arteries supplying the heart and brain, respectively. In type 2 diabetes (DM2) insulin is insufficient to maintain normal blood glucose. South Asians have high susceptibility to these diseases. Drawing upon the scientific literature and discussions with 22 internationally recognized scholars, this book focuses on causal explanations and their implications for prevention and research. Genetically based hypotheses are considered together with the developmental origins of health and disease (DOHAD) family of hypotheses. The book then considers how CHD, stroke, and DM2 are closely linked to rising affluence and the accompanying changes in life-expectancy and lifestyles. The established causal factors are shown to be insufficient, though necessary, parts of a convincing explanation for the excess of DM2 and CVD in South Asians. In identifying new explanations, this book emphasizes glycation of tissues, possibly leading to arterial stiffness and microcirculatory damage. In addition to endothelial pathways to atherosclerosis an external (adventitial) one is proposed, i.e. microcirculatory damage to the network of arterioles that nourish the coronary arteries. In addition to the ectopic fat in their liver and pancreas as the cause of beta cell dysfunction leading to DM2, additional ideas are proposed, i.e. microcirculatory damage. The high risk of CVD and DM2 in urbanizing South Asians is not inevitable, innate or genetic, or acquired in early life and programmed in a fixed way. Rather, exposure to risk factors in childhood, adolescence, and most particularly in adulthood is the key. The challenge to produce focused, low cost, effective actions, underpinned by clear, simple, and accurate explanations of the causes of the phenomenon is addressed.

83-OR: Pancreatic Exocrine to Endocrine Cell Cross Talk Mediates Endoplasmic Reticulum Stress and Beta-Cell Dysfunction in MODY8

Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 83-OR
Author(s):  
SEVIM KAHRAMAN ◽  
DANIELLE DIEGISSER ◽  
BENTE B. JOHANSSON ◽  
ANDERS MOLVEN ◽  
ROHIT KULKARNI
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Beta Cell ◽  
Cross Talk ◽  
Endocrine Cell ◽  
Beta Cell Dysfunction ◽  
Cell Dysfunction ◽  
Pancreatic Exocrine

Autoimmunity to insulin, beta cell dysfunction, and development of insulin-dependent diabetes mellitus

Diabetes ◽  
1986 ◽  
Vol 35 (2) ◽  
pp. 139-142 ◽  
Author(s):  
S. Srikanta ◽  
A. T. Ricker ◽  
D. K. McCulloch ◽  
J. S. Soeldner ◽  
G. S. Eisenbarth ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Beta Cell ◽  
Insulin Dependent Diabetes Mellitus ◽  
Insulin Dependent Diabetes ◽  
Dependent Diabetes Mellitus ◽  
Beta Cell Dysfunction ◽  
Cell Dysfunction ◽  
Insulin Dependent

Comparison of Sleeve Gastrectomy and Conservatory Treatment Effect on Biochemical and Hormonal Profile of Obese Type 2 Diabetes Subjects: CREDOR Randomized Controlled Study Results

2017 ◽  
Vol 68 (7) ◽  
pp. 1622-1627 ◽  
Author(s):  
Diana Simona Stefan ◽  
Andrada Mihai ◽  
Daiana Bajko ◽  
Daniela Lixandru ◽  
Laura Petcu ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Weight Loss ◽  
Sleeve Gastrectomy ◽  
Beta Cell ◽  
Beta Cell Dysfunction ◽  
Control Group ◽  
Cell Dysfunction ◽  
Randomized Controlled

Metabolic surgery is the most efficacious method for the treatment of morbid obesity and was recently included among the antidiabetes treatments recommended in obese type 2 diabetes (T2D) patients. The aim of this study was to compare in a randomized controlled trial the effect of sleeve gastrectomy (SG) to that of intensive lifestyle intervention plus pharmacologic treatment on some markers of insulin resistance and beta cell function as well as some appetite controlling hormones in a group of male obese T2D subjects. The study groups comprised 20 subjects for SG and 21 control subjects. Fasting blood glucose, insulin, proinsulin, adiponectin, leptin, ghrelin, HOMA-IR, HOMA-%B, proinsulin-to-insulin ratio and proinsulin-to-adiponectin ratio were evaluated at baseline and after one year follow-up. Overall, patients in the SG group lost 78.98% of excess weight loss (%EWL) in comparison with 9.45% in the control group. This was accompanied by a significant improvement of insulin resistance markers, including increase of adiponectin and decrease of HOMA-IR, while no changes were recorded in the control group. Weight loss was also associated with a significant improvement of proinsulin-to-insulin and proinsulin-to-adiponectin ratio, both surrogate markers of beta cell dysfunction. These also improved in the control group, but were only marginally significant. Our findings suggest that improved insulin resistance and decreased beta cell dysfunction after sleeve gastrectomy might explain diabetes remission associated with metabolic surgery.

scholarly journals Effects of DHMEQ, a Novel Nuclear Factor-κB Inhibitor, on Beta Cell Dysfunction in INS-1 Cells

2008 ◽  
Vol 55 (2) ◽  
pp. 433-438 ◽  
Author(s):  
Yoshifumi SAISHO ◽  
Hiroshi HIROSE ◽  
Chihiro HORIMAI ◽  
Kiichi MIYASHITA ◽  
Izumi TAKEI ◽  
...  
Keyword(s):  
Beta Cell ◽  
Nuclear Factor Κb ◽  
Beta Cell Dysfunction ◽  
Nuclear Factor ◽  
Cell Dysfunction

scholarly journals Selective inhibition of 12-lipoxygenase protects islets and beta cells from inflammatory cytokine-mediated beta cell dysfunction

Diabetologia ◽  
2014 ◽  
Vol 58 (3) ◽  
pp. 549-557 ◽  
Author(s):  
David A. Taylor-Fishwick ◽  
Jessica Weaver ◽  
Lindsey Glenn ◽  
Norine Kuhn ◽  
Ganesha Rai ◽  
...  
Keyword(s):  
Beta Cell ◽  
Beta Cells ◽  
Inflammatory Cytokine ◽  
Selective Inhibition ◽  
Beta Cell Dysfunction ◽  
Cell Dysfunction ◽  
12 Lipoxygenase

scholarly journals Incidence of diabetes in South Asian young adults compared to Pima Indians

2021 ◽  
Vol 9 (1) ◽  
pp. e001988
Author(s):  
K M Venkat Narayan ◽  
Dimple Kondal ◽  
Sayuko Kobes ◽  
Lisa R Staimez ◽  
Deepa Mohan ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Secretion ◽  
South Asians ◽  
Diabetes Incidence ◽  
Pima Indians ◽  
Men And Women ◽  
High Prevalence ◽  
History Of ◽  
Indian Men ◽  
Design And Methods

IntroductionSouth Asians (SA) and Pima Indians have high prevalence of diabetes but differ markedly in body size. We hypothesize that young SA will have higher diabetes incidence than Pima Indians at comparable body mass index (BMI) levels.Research design and methodsWe used prospective cohort data to estimate age-specific, sex, and BMI-specific diabetes incidence in SA aged 20–44 years living in India and Pakistan from the Center for Cardiometabolic Risk Reduction in South Asia Study (n=6676), and compared with Pima Indians, from Pima Indian Study (n=1852).ResultsAt baseline, SA were considerably less obese than Pima Indians (BMI (kg/m2): 24.4 vs 33.8; waist circumference (cm): 82.5 vs 107.0). Age-standardized diabetes incidence (cases/1000 person-years, 95% CI) was lower in SA than in Pima Indians (men: 14.2, 12.2–16.2 vs 37.3, 31.8–42.8; women: 14.8, 13.0–16.5 vs 46.1, 41.2–51.1). Risk of incident diabetes among 20–24-year-old Pima men and women was six times (relative risk (RR), 95% CI: 6.04, 3.30 to 12.0) and seven times (RR, 95% CI: 7.64, 3.73 to 18.2) higher as compared with SA men and women, respectively. In those with BMI <25 kg/m2, however, the risk of diabetes was over five times in SA men than in Pima Indian men. Among those with BMI ≥30 kg/m2, diabetes incidence in SA men was nearly as high as in Pima men. SA and Pima Indians had similar magnitude of association between age, sex, BMI, and insulin secretion with diabetes. The effect of family history was larger in SA, whereas that of insulin resistance was larger in Pima IndiansConclusionsIn the background of relatively low insulin resistance, higher diabetes incidence in SA is driven by poor insulin secretion in SA men. The findings call for research to improve insulin secretion in early natural history of diabetes.

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