[{"id":127,"title":"Why is the rate of incidence of diabetes increasing?","sha":"6be084816b1ad13ad3c22d11aa7b81f4","user_id":506,"state":"published","body":"The increasing rate of diabetes, often attributed to overweight associated with hypercaloric diets, has led to numerous dietary and lifestyle intervention trials. In these, the dietary components have focused particularly on controlling caloric intake through reduced fat or sugars [1](http://linkinghub.elsevier.com/retrieve/pii/S0140673601054150), [2](http://care.diabetesjournals.org/cgi/doi/10.2337/dc11-0442), [3](http://www.nature.com/doifinder/10.1038/sj.ijo.0801451), [4](http://linkinghub.elsevier.com/retrieve/pii/S0002822310006449). No firm conclusions have emerged.\r\n\r\nWhat appears to be overlooked is the role of high glycemic load _combined_ with a hypercaloric diet. This dietary pattern is exacerbated by focus on reducing saturated fat consumption, and drives metabolism towards android obesity and subsequent diabetes.\r\n\r\nSignificant caloric restriction reverses biochemical markers of insulin resistance [5](http://link.springer.com/10.1007/s00125-011-2204-7). Diets favoring calories from carbohydrate rather than fat lead towards markers, especially dislipidemia, typical of pre-diabetes in an iso- or hypercaloric state [6](http://care.diabetesjournals.org/cgi/doi/10.2337/dc06-2220), [7](http://ajcn.nutrition.org/cgi/doi/10.3945/ajcn.113.081521), [8](http://dx.plos.org/10.1371/journal.pone.0113605). The mechanism probably involves de novo lipogenesis from glucose in the liver and pancreatic β-cells.\r\n\r\nRestricted caloric intake, especially via very low fat consumption, can delay or reverse the onset of diabetes, but has not proven a sustainable long-term diet. Focusing instead on hypo- or isocaloric diets with very low glycemic load (low carbohydrate), is both feasible in the long-term [9](http://www.diabetes-book.com/diabetes-diet/), and addresses factors leading to obesity and overt diabetes.\r\n","created_at":"2015-03-25T08:16:50.291Z","updated_at":"2015-04-07T04:08:46.729Z","zenodo_id":25609,"doi":"http://dx.doi.org/10.5281/zenodo.16337","subject":null,"tags":["healthcare","food","diabetes"],"vote_count":3,"view_count":1,"score":3.1,"deleted":false,"muted":false,"tweeted":true,"attachment_file_name":null,"attachment_content_type":null,"attachment_file_size":null,"attachment_updated_at":null},{"id":150,"title":"Is exogenous insulin inevitable for diabetics?","sha":"b37228d662c7ee3d93b8679a9488a21c","user_id":506,"state":"published","body":"Endogenous insulin production ceases with the loss of pancreatic islet β-cells, caused by autoimmune antibodies [1, ](http://dx.doi.org/10.1016/S0140-6736(01)05415-0)[2, ](http://dx.doi.org/10.1016/j.lpm.2012.10.003)[3](http://www.mlo-online.com/articles/201310/the-clinical-application-of-islet-autoantibody-testing-for-the-diagnosis-of-autoimmune-diabetes.php) and fatty acids [4, ](http://dx.doi.org/10.1042/CS20060115)[5](http://dx.doi.org/10.1111/j.1463-1326.2010.01265.x). Thus the presence of high-titre islet cell antibodies may foreshadow loss of residual β-cell function and subsequently reduced (endogenous) insulin production [6](http://dx.doi.org/10.2337/diacare.23.8.1072). Given that insulin, and its precursors, is the initial antigen [2, ](http://dx.doi.org/10.1016/j.lpm.2012.10.003)[7](http://dx.doi.org/10.1210/er.2011-0010), metabolic circumstances resulting in hyperinsulinism may lead to overt diabetes via both antibody production and dislipidemia. \r\n\r\nReports that long-term insulin dependence does not eliminate endogenous insulin secretion completely [8](http://dx.doi.org/10.2337/dc14-0871), that β-cells may undergo significant cell proliferation [9](http://dx.doi.org/10.1007/s00125-010-1817-6), and that at least some antibodies have limited persistence [1, ](http://dx.doi.org/10.1016/S0140-6736(01)05415-0)[3](http://www.mlo-online.com/articles/201310/the-clinical-application-of-islet-autoantibody-testing-for-the-diagnosis-of-autoimmune-diabetes.php), suggests that preventing continued autoimmune antibody production may ultimately restore normal insulin activity. \r\n\r\nAn alternative to managing diabetes with exogenous insulin is to reduce the glycemic load appropriate to the residual insulin activity still available [10](http://dx.doi.org/10.5281/zenodo.16337). In early stages of diabetes, it seems logical that removing the antigen trigger (excess insulin in the β-cells) may allow a natural decline in antibodies and thus extend the timeframe to overt diabetes or potentially even prevent β-cell loss. Could a similar pathway also reverse long-term insulin-dependent diabetes?\r\n","created_at":"2015-04-18T02:13:06.207Z","updated_at":"2015-04-20T02:18:40.159Z","zenodo_id":27267,"doi":"http://dx.doi.org/10.5281/zenodo.16934","subject":null,"tags":["insulin","diabetes","glycemic load","carbohydrate"],"vote_count":3,"view_count":1,"score":3.1,"deleted":false,"muted":false,"tweeted":true,"attachment_file_name":null,"attachment_content_type":null,"attachment_file_size":null,"attachment_updated_at":null},{"id":256,"title":"Hyperglycaemia: both cause and effect of diabetes","sha":"ff7941c7cb69f9752eaddde07d7adf6b","user_id":null,"state":"published","body":"Current thinking suggests diabetes has variable causes, is inevitably progressive, and causes hyperglycaemia. **Type 1** is an autoimmune disease causing β-cell (source of insulin) death, and **type 2** is an insulin activity deficiency (insulin resistance)\u003csup\u003e[1](http://linkinghub.elsevier.com/retrieve/pii/S1538544212001149),[2](http://linkinghub.elsevier.com/retrieve/pii/S0140673613605917),[3](http://link.springer.com/10.1007/s00125-011-2204-7),[4](http://linkinghub.elsevier.com/retrieve/pii/S0026049515002565)\u003c/sup\u003e.  I propose that an excessive carbohydrate intake, inducing raised blood glucose (hyperglycaemia), is instead the starting point for both types. This modifies the accelerator hypothesis\u003csup\u003e[5](http://www.nature.com/doifinder/10.1038/ijo.2009.97)\u003c/sup\u003e, replacing insulin resistance with hyperglycemia.  \r\n\r\nAutoantibodies (probably derived from chronic raised demand for insulin, which is itself a significant antigen\u003csup\u003e[6](http://perspectivesinmedicine.cshlp.org/lookup/doi/10.1101/cshperspect.a007658)\u003c/sup\u003e) are only weakly predictive for diabetes\u003csup\u003e[7](http://linkinghub.elsevier.com/retrieve/pii/S1074761310001251)\u003c/sup\u003e. Hyperglycaemia directly reduces insulin production\u003csup\u003e[8](http://www.nature.com/doifinder/10.1038/ncomms5639)\u003c/sup\u003e and also induces β-cell death\u003csup\u003e[9](http://diabetes.diabetesjournals.org/cgi/doi/10.2337/diabetes.50.6.1290)\u003c/sup\u003e, suggesting other routes to loss of insulin production (type 1).\r\n\r\nCells become insulin resistant (unable to take up glucose) with high serum lipids (fats). These lipids are associated with high-calorie/high-carbohydrate diets\u003csup\u003e[4](http://linkinghub.elsevier.com/retrieve/pii/S0026049515002565),[10](http://ajcn.nutrition.org/content/48/2/240.long),[11](http://www.jlr.org/content/39/6/1280.short)\u003c/sup\u003e. Insulin resistance has been demonstrated to be reversible with low-carbohydrate and weight loss diets\u003csup\u003e[3](http://link.springer.com/10.1007/s00125-011-2204-7),[12](http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1188071/),[13](http://diabetes.diabetesjournals.org/cgi/doi/10.2337/diabetes.54.3.603)\u003c/sup\u003e.  \r\n\r\nExcessive carbohydrate (starch and sugar) intake, more than can be metabolised or stored as glycogen or lipids, leaves the excess glucose in the blood. This hyperglycaemia (initiated by intermittent or chronic excess carbohydrate) actually causes diabetes through a cascade of events leading to insulin deficiency (type 1) or impairment (type 2). \r\n","created_at":"2015-11-21T01:18:52.391Z","updated_at":"2015-11-21T06:00:46.226Z","zenodo_id":70096,"doi":"http://dx.doi.org/10.5281/zenodo.34078","subject":null,"tags":["diabetes","hyperglycaemia"],"vote_count":0,"view_count":1,"score":0.1,"deleted":false,"muted":false,"tweeted":true,"attachment_file_name":null,"attachment_content_type":null,"attachment_file_size":null,"attachment_updated_at":null},{"id":321,"title":"Diabetes screening using home blood glucose meter testing during the Dawn Phenomenon period","sha":"9461590ffe1e5323abda7855aa799f6c","user_id":null,"state":"published","body":"The Dawn Phenomenon (DP) was first noted in diabetics as an unexpected increase in blood glucose beginning during sleep early in the morning\u003csup\u003e[1](http://dx.doi.org/10.2337/diacare.4.6.579)\u003c/sup\u003e. The glucose is derived from increased hepatic gluconeogenesis rather than reduced glucose use and the diabetic state is considered an exaggeration of a natural circadian rhythm\u003csup\u003e[2](http://dx.doi.org/10.2337/diacare.7.1.32)\u003c/sup\u003e. Non-diabetics exhibit an increase in insulin while remaining normoglycaemic\u003csup\u003e[3]( http://dx.doi.org/10.2337/diab.33.12.1150)\u003c/sup\u003e, but diabetics show little change in insulin secretion\u003csup\u003e[2](http:// dx.doi.org/10.2337/diacare.7.1.32)\u003c/sup\u003e.  This suggests a failure in insulin secretion response to endogenous glucose supply rather than any change in insulin activity itself. \r\n\r\nThe glucose response period is most commonly from 7 – 9 a.m. The glucose increase in non-diabetics is subtle, up to 0.5 mmol/L (9.9 mg/dL), while for diabetics it is commonly 1 – 5 mmol/L (18 – 90 mg/dL)\u003csup\u003e[2]( http://dx.doi.org/10.2337/diacare.7.1.32)\u003c/sup\u003e\u003csup\u003e, [4]( http://dx.doi.org/10.2337/dc13-2088)\u003c/sup\u003e. Home blood glucose monitors are precise enough to report a diabetic Dawn Phenomenon pattern.  This raises the potential to reduce cost and inconvenience to patients by implementing a self-testing method for routine screening purposes. Two finger-prick tests 1 – 2 hours apart within the 7 – 9 a.m. period are likely to be sufficient, although 3 – 4 tests at half to one hour intervals would be better.\r\n","created_at":"2016-07-17T22:03:50.157Z","updated_at":"2016-07-18T06:00:25.388Z","zenodo_id":130676,"doi":"http://dx.doi.org/10.5281/zenodo.58070","subject":null,"tags":["diabetes","serum glucose"],"vote_count":0,"view_count":1,"score":0.1,"deleted":false,"muted":false,"tweeted":true,"attachment_file_name":null,"attachment_content_type":null,"attachment_file_size":null,"attachment_updated_at":null}]