The key research papers and other sources of information for Get Tough are given below, organised by chapter. As explained in the Introduction, I have focused on sources that are ‘open access’ (they are free to read in full online) but on occasion papers that are behind a pay-wall are so important that I have included them also. For research papers I have cited the traditional identifiers (author names, article title, journal name etc) together with the ‘DOI’ – digital object identifier, which is the unique number for any online publication (many older articles do not have one) – and the ‘PubMed’ number which will allow you to find the ‘Abstract’ (summary) of any research paper on www.pubmed.gov.
For my discussion of the change in HbA1c measurements:
Levy D. HbA1c: changing units, changing minds – mission accomplished? British Journal of Diabetes & Vascular Disease 2013; 13(3): 111-114. DOI: 10.1177/1474651413495901
The ‘twin cycle’ hypothesis is the name given to the current thinking behind the cause of Type 2 diabetes, ‘twin’ referring to metabolic pathways in the liver and the pancreas. The ‘twin cycle’ idea is especially associated with Newcastle University and the ultra-low-calorie diet used in their pioneering studies (see Chapter 4). There are surprisingly few references suitable for non-scientists, but there are a few slides available at the following web address:
www.ncl.ac.uk/media/wwwnclacuk/newcastlemagneticresonancecentre/files/fat-threshholds-slides.pdf (accessed 20 December 2017).
There is a medical review paper on the twin cycle hypothesis and reversing it in the journal Diabetic Medicine by Professor Roy Taylor who leads the Newcastle projects:
Taylor R. Banting Memorial Lecture 2012: Reversing the twin cycles of Type 2 diabetes. Diabetic Medicine 2013; 30(3): 267-275. DOI: 10.1111/dme.12039. PubMed reference number 23075228. Free full text.
The Whitehall study in which civil servants were followed up with annual blood glucose levels. An analysis of ethnic differences found that south Asian people began their long journey towards diabetes with a slightly higher glucose level than white subjects, and the rise in the two years before diagnosis was slightly more rapid:
Hulman A, Simmons RK, Brunner EJ, Witte DR, et al. Trajectories of glycaemia, insulin sensitivity and insulin secretion in South Asian and white individuals before diagnosis of type 2 diabetes: a longitudinal analysis from the Whitehall II cohort study. Diabetologia 2017; 60(7): 1252-1260. doi: 10.1007/s00125-017-4275-6 PubMed reference number 23075228. Free full text.
To estimate your risk of Type 2 go to the Diabetes UK website:
Estimating your risk of diabetes. https://riskscore.diabetes.org.uk/ (accessed 20 December 2017).
There is a fully open-access journal devoted to the metabolic syndrome, the Journal of Metabolic Syndrome, with many links, mostly scientific, but a few of clinical interest:
www.omicsonline.org/ArchiveJMS/articleinpress-metabolic-syndrome-open-access.php (accessed 20 December 2017).
The argument/discussion about the ‘definition’ of the metabolic syndrome has been rumbling on for years. It is mostly concerned with ‘cut off points’ for glucose, blood pressure, waist measurements and lipid values as these are the easily measurable characteristics of the syndrome. The International Diabetes Federation issued their most recent document in 2014:
IDF (2006) The IDF consensus worldwide definition of the Metabolic Syndrome. www.idf.org/e-library/consensus-statements/60-idfconsensus-worldwide-definitionof-the-metabolic-syndrome.html (accessed 21 December 2017).
There have been various clinical trials, mostly from the 1980s–2000s, that attempted to reduce the risk of progression from pre-diabetic blood glucose levels to diabetes itself. In particular:
For more on treatment I suggest:
Hsu WF, S LY, Lin HJ, Chang HH. A review of western and traditional Chinese medical approaches to managing nonalcoholic fatty liver disease. Evidence Based Complementary and Alternative Medicine 2016, Article ID 6491420, 12 pages. DOI.org/10.1155/2016/6491420. PubMed reference number: 27872651. Free full text.
A scientific review of complementary treatments, concluded, like they nearly all have to for nearly every condition, that there is suggestive evidence for benefit, but not yet supported by sufficiently rigorous clinical trials:
Arentz S, Smith CA, Abbott J, Bensoussan A. Nutritional supplements and herbal medicines for women with polycystic ovary syndrome; a systematic review and meta-analysis. BMC Complementary and Alternative Medicine 2017; 17(1): 500. DOI: 10.1186/s12906-017-2011-x. PubMed reference number: 29178904. Free full text.
For the effect of CPAP treatment on cardiovascular outcomes in people with obstructive sleep apnoea see:
McEvoy RD, Antic NA, Heeley E, Luo Y, et al. CPAP for prevention of cardiovascular events in obstructive sleep apnea. New England Journal of Medicine 2016; 375: 919-931. DOI: 10.1056/NEJMoa1606599. PMID Reference number: 27571048. Free full text.
There is very little scientific literature on non-drug treatment of gout, and this in part reflects the very effective medication available. This is an article written for general practitioners in the USA:
Hainer BL, Matheson E, Wilkes RT. Diagnosis, treatment, and prevention of gout. American Family Physician 2014; 90(12): 831-836. PubMed reference number: 25591183.
The original research paper on the Newcastle approach to Type 2 was published in 2011. It is known as The Counterbalance study (COUNTERacting BetA cell failure by Long term Action to Normalise Calorie intakE):
Lim EL, Hollingsworth KG, Aribisala BS, Chen MJ, Mathers JC, Taylor R. Reversal of type 2 diabetes: normalisation of beta cell function in association with decreased pancreas and liver triacylglycerol. Diabetologia 2011; 54(10): 2506-2514. DOI: 10.1007/s00125-011-2204-7 PubMed reference number: 21656330. Free full text.
The follow-up paper using the same dietary approach in people with both short- and long-duration diabetes was published in 2016:
Stevens S, Hollingsworth KG, Al-Mrabeth A, Avery L, et al. Very low-calorie diet and 6 months of weight stability in Type 2 diabetes: pathophysiological changes in responders and nonresponders. Diabetes Care 2016; 39(5): 808-815. DOI: 10.2337/dc15-1942. PubMed reference number: 27002059 (abstract only, not full text).
The DiRECT study, which reported extending this initially experimental approach to a much larger group of Type 2s, was published in 2017:
Lean MEJ, Leslie WS, Barnes AC, Brosnahan N, et al. Primary care-led weight management for remission of type 2 diabetes (DiRECT): an open-label, cluster-randomised trial. Lancet 2018; 391(10120):541-551. DOI: org/10.1016/S0140-6736(17)33102-1. PubMed reference number: 29221645 (abstract only).
There are no easily available full-text reports of the UKPDS, but there is a valuable website of the Oxford research unit where the UKPDS (and many other studies) have been carried out:
www.dtu.ox.ac.uk/UKPDS/ (accessed 28 December 2017).
The reference for this study is:
The Look AHEAD Reaearch Group. Cardiovascular effects of intensive lifestyle intervention in type 2 diabetes. New England Journal of Medicine 2013; 369: 145-154. DOI: 10.1056/NEJMoa1212914 PubMed reference number: 23796131. Free full text.
This trio of major trials was published between 2008 and 2010. These studies were designed after UKPDS reported its main results in 1998. In UKPDS, reducing average blood glucose levels over several years from about 8% (64 mmol/mol) to 7% (53 mmol/mol) slightly reduced the risk of a heart attack. The following trials attempted to find out whether this effect was consistent. Participants were large groups of Type 2 people in their 60s, with about 10 years of diabetes, many of whom had evidence of a previous stroke or heart disease, so they were at higher risk of another event. In each trial, one group was given intensive education and treatment to reduce overall glucose levels, while the other group was given more routine levels of care. They continued for between 6 and 10 years. Broadly, they showed that improved glucose control – in some cases near-normal glucose values – had no meaningful effect on reducing these diabetic complications (one, ACCORD, detected increased harm in the intensively treated people who were often taking multiple glucose-lowering medications). Some showed a slight benefit in kidney disease. After very long-term follow-up there were detectable but small reductions in heart attack rates. The results of these very important trials never really made the headlines, perhaps in part because they didn’t support the idea that very low glucose levels improved long-term complications. But this shouldn’t be a surprise: Type 2 is much more than just high blood glucose control. More surprising were the additional findings that lowering blood pressure and intensifying cholesterol treatment also didn’t have major effects on complications.
The reference for the ACCORD study is:
The ACCORD Study Group. Effects of intensive glucose lowering in type 2 diabetes New England Journal of Medicine 2008; 358: 2545-2559. DOI: 10.1056/NEJMoa0802743. PubMed reference number: 18539917. Free full text.
The reference for the long-term ACCORD follow-up study is:
The ACCORD Study Group. Long-term effects of intensive glucose lowering on cardiovascular outcomes. New England Journal of Medicine 2011; 364: 818-828. DOI: 10.1056/NEJMoa1006524. PubMed reference number: 21366473. Free full text.
The reference for the ADVANCE study is:
ADVANCE Collaborative Group. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. New England Journal of Medicine 2008; 358(24): 2560-2572. DOI: 10.1056/NEJMoa0802987. PubMed reference number: 18539916. Free full text.
The reference for the long-term follow-up is:
Zoungas S, Chalmers J, Neal B, Billot L, et al. Follow-up of blood-pressure lowering and glucose control in type 2 diabetes. New England Journal of Medicine 2014; 371: 1392-1406. DOI: 10.1056/NEJMoa1407963. PubMed reference number: 25234206. Free full text.
The reference for the VADT study is:
Duckworth W, Abraira C, Moritz T, Reda D, et al. Glucose control and vascular complications in veterans with type 2 diabetes. New England Journal of Medicine 2009; 360: 129-139. DOI: 10.1056/NEJMoa0808431. PubMed reference number: 19092145. Free full text.
This is a famous multimodal interventional study (medication and lifestyle) in Danish Type 2 people with minor kidney involvement caused by diabetes. Below is the reference to the most recent report, showing that the intensively treated patient group had fewer heart attacks, fewer overall diabetes complications and longer life expectancy. Blood glucose control was not especially good (HbA1c 7.7%, 61 mmol/mol): the portfolio approach works well.
Gaede P, Oellgaard J, Carstensen B, Rossing P, et al. Years of life gained by multifactorial intervention in patients with type 2 diabetes mellitus and microalbuminuria: 21 years follow-up on the Steno-2 randomised trial. Diabetologia 2016; 59(11): 2298-2307. DOI: 10.1007/s00125-016-4065-6. PubMed reference number: 27531506. Free full text.
The following references all relate to studies of diet discussed within the chapter.
DIOGENES:
Larsen TM, Dalskov SM, van Baak M, Papdaki A, et al: Diet, Obesity and Genese (Diogenes) Project. Diets with high or low protein content and glycemic index for weight-loss maintenance. New England Journal of Medicine 2010; 363(22): 2102-2113. DOI: 10.1056/NEJMoa1007137. PubMed reference number: 21105792. Free full text.
DiRECT trial:
Shai I, Schwarzfuchs D, Henkin Y, Shahar DR, et al: DiRECT group. Weight loss with a low-carbohydrate, Mediterranean, or low-fat diet. New England Journal of Medicine 2008; 359: 229-241. DOI: 10.1056/NEJMoa0708681. PubMed reference number: 18635428. Free full text.
Lyon Diet Heart study:
de Lorgeril M, Salen P, Martin J-L, Monjaud I, Delaye J, Mamelle N. Mediterranean diet, traditional risk factors, and the rate of cardiovascular complications after myocardial infarction: final report of the Lyon Diet Heart Study. Circulation 1999; 99: 779-785. DOI: org/10.1161/01.CIR.99.6.779. PubMed reference number: 9989963. Free full text.
PREDIMED study:
Estruch R, Ros E, Salas-Salvado J, Covas M-I, et al. Primary prevention of cardiovascular disease with a Mediterranean diet. New England Journal of Medicine 2013; 368: 1279-1290. DOI: 10.1056/NEJMoa1200303. PubMed reference number: 23432189. Free full text.
Mediterranean diet in Greece:
Trichopoulou A, Costacou T, Bamia C, Trichopoulos D. Adherence to a Mediterranean diet and survival in a Greek population. New England Journal of Medicine 2003; 348(26): 2599-2608. DOI: 10.1056/NEJMoa025039. PubMed reference number: 12826634. Free full text.
Low glycaemic index carbohydrates in Type 2 diabetes:
Wolever TM, Gibbs AL, Mehling C, Chiasson JL, et al. The Canadian Trial of Carbohydrates in Diabetes (CCD), a 1-y controlled trial of low-glycemic-index dietary carbohydrate in type 2 diabetes: no effect on glycated haemoglobin but reduction in C-reactive protein. American Journal of Clinical Nutrition 2008; 87(1): 114-125. PubMed Reference number: 18175744. Free full text.
Carbohydrates, saturated fat and cardiovascular disease (PURE study):
Dehghan M, Mente A, Zhang X, Swiminathan S, et al. Associations of fats and carbohydrate intake with cardiovascular disease and mortality in 18 countries from five continents (PURE): a prospective cohort study. Lancet 2017; 390(10107): 2050-2062. DOI: http://dx.doi.org/10.1016/S0140-6736(17)32252-3. PubMed reference number: 28864332. Abstract only.
A relatively new concept is ‘ultra-processed’ food, which has recently been identified as a serious risk factor for obesity in the population in general, and very likely for Type 2 as well. Ultra-processed foods are pre-packaged and made mostly from artificial products, often with only a small proportion of ingredients that you could buy or prepare yourself. Examples include carbonated drinks, mass-produced packaged breads and buns, margarines, cakes, breakfast cereals and energy bars, energy and milk drinks, fruit yoghurts and drinks, and many ready-to-heat products, including pies, pasta and pizzas, burgers and instant soups. In a 2018 report, about 50% of food in UK households was ultra-processed – the highest proportion out of 19 European countries. In Mediterranean countries the proportion was much lower – for example, 10% in Portugal, 13% in Italy and 14% in France. This is another powerful endorsement of the benefits of the home-cooked Mediterranean diet.
Monteiro CA, Moubarac JC, Levy RB, Canella DS, Louzada MLDC, Cannon G. Household availability of ultra-processed foods and obesity in nineteen European countries. Public Health Nutrition 2018; 21(1): 18-26. DOI: 10. 1017/S1368980017001379. PubMed reference number: 28714422. Abstract only.
The following book provides an astonishingly simple and effective pictorial way of estimating the calorie, fat and carbohydrate content of thousands of foods and food products, taking into account portion size:
Cheyette C, Balolia Y. Carbs & Cals: Carb & Calorie Counter. 6th ed. London: Chello Publishing; 2016.
There is an authoritative website sponsored by a division of the National Institutes of Health in the USA – the Office of Dietary Supplements. Every supplement has a full article which summarises all the evidence on a particular food or supplement, and draws some conclusions on its potential clinical value. Although the website is intended for professionals, it is well written and easy to understand. Because it’s limited to assessing available evidence, you’ll understand this is not the site to go to if you want to find hype on the latest superfood:
https://ods.od.nih.gov/factsheets (accessed 31 December 2017).
WebMD is also a reliable source:
www.WebMD.com (accessed 31 December 2017).
This is a careful recent study. Chromium nicotinate taken for three months had no effect on several important measurements in Type 2 diabetes (glucose, insulin effectiveness, weight, waist measurement):
Guimaraes MM, Carvalho AC, Silva MS. Effect of chromium supplementation on the glucose homeostasis and anthropometry of type 2 diabetic patients. Journal of Trace Elements in Medicine and Biology 2016; 36: 65-72. DOI: 10.1016/j.jtemb.2016.04.002 PubMed reference number: 27259354. Abstract only.
The website of the COSMOS trial of cocoa supplements (COcoa Supplement and Multivitamin Outcomes Study (COSMOS) is:
www.cosmostrial.org/ (accessed 24 December 2017).
There is good evidence that resveratrol does not improve metabolic health in Type 2 diabetes:
Timmers S, de Ligt M, van de Weijer T, Hansen J, et al. Resveratrol as add-on therapy in subjects with well-controlled type 2 diabetes: a randomized controlled trial. Diabetes Care 2016; 39(12): 2211-2217. DOI: 10.2337/dc16-0499. PubMed reference number: 27852684. Abstract only.
In most, but not all, studies, vinegar taken with high-glycaemic index foods reduces the blood glucose level after the meal. This is a neat and well-conducted study:
Liatis S, Grammatikou S, Poulia KA, et al. Vinegar decreases postprandial hyperglycemia in patients with type II diabetes when added to a high, but not to a low, glycemic index meal. European Journal of Clinical Nutrition 2010; 64(7): 727-732. DOI: 10.1038/ejcn.2010.89. PubMed reference number: 20502468. Abstract only.
Intensive lifestyle intervention and drug treatment can be equally beneficial in reducing blood pressure – a comparison of Look AHEAD (lifestyle) and ACCORD (drug treatment):
Espeland MA, Probstfield J, Hire D, Redmon JB, et al. Systolic blood pressure control among individuals with type 2 diabetes: a comparative effectiveness analysis of three interventions. American Journal of Hypertension 2015; 28(8): 995-1009. DOI: 10.1093/ajh/hpu292. PubMed reference number: 25666468. Free full text.
For the DASH diet for hypertension see:
www.dashdiet.org (accessed 31 December 2017).
This is the report of the original DASH study (1997):
Appel LJ, Moore TJ, Obarzanek E, Vollmer WM, et al. A clinical trial of the effects of dietary patterns on blood pressure. DASH Collaborative Research Group. New England Journal of Medicine 1997; 336(16): 117-1124. PubMed reference number: 9099655. Free full text.
This is a general review of their role in the prevention of vascular disease:
Sosnowska B, Penson P, Banach M. The role of nutraceuticals in the prevention of cardiovascular disease Cardiovascular Diagnosis and Therapy 2017; 7(Suppl 1): S21-S31. DOI: 10.21037/cdt.2017.03.20. PubMed reference number: 28529919. Free full text.
For nutraceuticals in the treatment of high cholesterol see:
Nutraceuticals in hypercholesterolaemia: an overview (British Journal of Pharmacology, 2017). PubMed reference number: 27685833. Free full text.
The science is established – too much salt is strongly associated with a higher risk of cardiovascular diseases – but the politics rumble on. This is a recent paper published in a journal of public health:
Reeve B, Magnusson R. Reprint of: food reformulation and the (neo)-liberal state: new strategies for strengthening voluntary salt reduction programs in the UK and USA. Public Health 2015; 129(8): 1061-1073. DOI: 10.1016/j.puhe.2015.04.021. PubMed reference number: 26027448. Free full text.
The World Health Organization web address where you can find their recommendations on activity levels for good health is:
www.who.int/topics/physical_activity/en/ (accessed 26 December 2017).
If you’re curious how many METs you expend raking your lawn (4.0) or playing guitar (standing) in your rock and roll band (3.0) – since you ask, the same as juggling – this is the super-official list:
http://prevention.sph.sc.edu/tools/docs/documents_compendium.pdf (accessed 26 December 2017)
Activity levels assessed at the beginning of the ADVANCE trial (see Chapter 5) and diabetes-related outcomes after an average follow-up of eight years are reported here:
Blomster JI, Chow CK, Zoungas S, Woodward M, et al. The influence of physical activity on vascular complications and mortality in patients with type 2 diabetes mellitus. Diabetes Obesity and Metabolism 2013; 15(11): 1008-1012. DOI: 10.1111/dom.12122. PubMed reference number: 23675676. Abstract only.
Reducing medication with exercise: a careful trial in Denmark, focusing on exercise (around six weekly aerobic sessions of 30–60 minutes, combined with anaerobic exercise in two or three of the sessions). Patients already had very good blood glucose control (average HbA1c 6.7%), so no meaningful improvements could be expected, but nearly three-quarters of the intensive lifestyle group reduced their diabetes medication, compared with only one-quarter of the group given routine care:
Johansen MY, MacDonald CS, Hansen KB, Karstoft K, et al. Effect of an intensive lifestyle intervention on glycemic control in patients with type 2 diabetes: a randomized clinical trial. Journal of the American Medical Association 2017; 18(7): 637-649. DOI: 10.1001/jama.2017.10169. PubMed reference number: 28810024. Abstract only.
Fitbits don’t increase physical activity in Singapore …
Finkelstein EA, Haaland BA, Bilger M, Sahasranaman A, et al. Effectiveness of activity trackers with and without incentives to increase physical activity (TRIPPA): a randomised controlled trial. Lancet Diabetes and Endocrinology 2016; 4(12): 983-995. DOI: 10.1016/S2213-8587(16)30284-4. PubMed reference number: 27717766. Abstract only.
… or in Canadian university students:
Sharp P, Caperchione C. The effects of a pedometer-based intervention on first-year university students: a randomized control trial. Journal of the American College of Health 2016; 64(8): 630-638. DOI: 10.1080/07448481.2016.1217538. PubMed reference number: 27471879. Abstract only.
Looking at the effect of intermittent exercise during an otherwise sedentary day – for example, at work – the following paper describes the beneficial effects of walking for about six minutes every hour on insulin and glucose levels in non-diabetic people. Standing up didn’t carry the same benefits:
Pulsford RM, Blackwell J, Hillsdon M, Kos K. Intermittent walking, but not standing, improves postprandial insulin and glucose relative to sustained sitting: a randomised cross-over study in inactive middle-aged men. Journal of Science and Medicine in Sport 2017; 20(3): 278-283. DOI: 10.1016/j.jsams.2016.08.012. PubMed reference number: 27633397. Abstract only.
Intermittent high intensity training improves heart function and structure, and reduces liver fat (by about 40%) in Type 2s. The study was done by the same Newcastle group who taught us about remission in Type 2 with very low-calorie diets:
Cassidy S, Thoma C, Hallsworth K, Parikh J, et al. High intensity intermittent exercise improves cardiac structure and function and reduces liver fat in patients with type 2 diabetes: a randomised controlled trial Diabetologia 2016; 59(1): 56-66. DOI: 10.1007/s00125-015-3741-2. PubMed reference number: 26350611. Free full text.
Reduction in major complications of Type 2 diabetes in the USA over the past 20 years are described here:
Gregg EW, Li Y, Wang J, Burrows NR, et al. Changes in diabetes-related complications in the United States, 1990–2010 New England Journal of Medicine 2014; 370(16): 1514-1523. DOI: 10.1056/NEJMoa1310799. PubMed reference number: 24738668. Free full access.
The first research paper shows that younger south Asians with heart disease now live longer than their white UK counterparts, indicating huge improvements in medical care and self-management over a relatively short period:
Wright AK, Kontopantelis E, Emsley R, Buchan I, et al. Life expectancy and cause-specific mortality in type 2 diabetes: a population-based cohort study quantifying relationships in ethnic subgroups. Diabetes Care 2017; 40(3): 338-345. DOI: 10.2337/dc16-1616. PubMed reference number: 27998911. Abstract only.
The second isn’t strictly related to heart disease but is a good reminder of the value of evidence over opinion. When exercise is measured objectively, south Asian people do as much as white UK people, but when asked to estimate their activity levels, don’t exaggerate as much (see also Chapter 8):
Yates T, Henson J, Edwardson C, Bodicoat DH, Davies MJ, Khunti K. Differences in levels of physical activity between white and south Asian populations within a healthcare setting: impact of measurement type in a cross-sectional study. BMJ Open 2015; 5(7): e006181. DOI: 10.1136/bmjopen-2014-006181. PubMed reference number: 26204908. Free full text.
In people with stable coronary artery disease involving two arteries, very intensive lifestyle management was equally effective compared with placing stents. This is the report of one of these studies, COURAGE:
Sedlis SP, Hartigan PM, Teo KK, Maron DJ, et al. Effect of PCI [percutaneous coronary intervention, that is stent placement] on long-term survival in patients with stable ischemic heart disease. New England Journal of Medicine 2015; 373(20): 1937-1946. DOI: 10.1056/NEJMoa1505532. PubMed reference number: 26559572. Free full text.
Intensive cardiac rehabilitation reduces the risk of further cardiac events and increases life expectancy:
Bittner V, Bertolet M, Barraza FR, Farkouh ME, et al (BARI 2D Study Group). Comprehensive cardiovascular risk factor control improves survival. Journal of the American College of Cardiology 2015; 66(7): 765-773. DOI: 10.1016/j. jacc.2015.06.019. PubMed reference number: 26271057. Free full text.
Using sophisticated cardiac screening tests to identify people with ‘silent’ coronary artery disease has not been shown to improve cardiac outcomes compared with people who had prompt access to the appropriate tests as soon as they developed symptoms. This is the report of one such trial, DIAD:
Young LH, Wackers FJ, Chyun DA, Davey JA, et al. Cardiac outcomes after screening for asymptomatic coronary artery disease in patients with type 2 diabetes: the DIAD study: a randomized controlled trial Journal of the American Medical Association 2009; 301(15): 1547-1555. DOI: 10.1001/jama.2009.476. PubMed reference number: 19366774. Free full text.
Self-assess your risk of developing heart disease. The huge UK QRISK database is regularly updated and is now in its third version (QRISK3):
https://qrisk.org/three/ (accessed 31 December 2017).
A list of blood pressure monitors recommended by the British Hypertension Society for use at home can be found here:
http://bhsoc.org/bp-monitors/bp-monitors/ (accessed 28 December 2017).
The importance of taking blood pressure treatment regularly (= ‘good/high adherence’) is supported by this study:
Kim S, Shin DW, Yun JM, Hwang Y, et al. Medication adherence and the risk of cardiovascular mortality and hospitalization among patients with newly prescribed antihypertensive medication. Hypertension 2016; 67(3): 506-512. DOI: 10.1161/HYPERTENSIONAHA.115.06731. PubMed reference number: 26865198. Abstract only.
Treatment of resistant hypertension has been studied extensively. This is one of a series of sophisticated clinical trials from the UK (the PATHWAY studies) that have used scientific understanding of hypertension to combine older antihypertensive drugs in clever new ways. The results are impressive, and have really helped people previously taking large bundles of blood pressure treatments, and often developing side-effects on them, with little impact on their blood pressure. (And they also feel much better with the new treatments.) This is another example of the real benefits of ‘thinking’ medicine:
Brown MJ, Williams B, Morant SV, Webb DJ, et al. Effect of amiloride, or amiloride plus hydrochlorothiazide, versus hydrochlorothiazide on glucose tolerance and blood pressure (PATHWAY-3): a parallel-group, double-blind randomised phase 4 trial. Lancet Diabetes and Endocrinology 2016; 4(2): 136-147. DOI: 10.1016/S2213-8587(15)00377-0. PubMed reference number: 26489809. Free full text.
The CARDS study was the first statin trial conducted in an otherwise well group of Type 2s without known heart disease or stroke:
Colhoun HM, Betteridge DJ, Durrington PN, Hitman GA, et al. Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomised placebo-controlled trial. Lancet 2004; 364(9435): 685-696. DOI: 10.1016/S0140-6736(04)16895-5. PubMed reference number: 15325833. (Abstract only. Sadly, 14 years after CARDS was published, the study is still not available in free full text form)
The evidence from Denmark is clear – after negative media stories about statins, some people discontinue taking statin treatment. Those with known heart disease are less likely to discontinue, but those with other blood vessel disorders and high blood pressure are more likely to discontinue:
Kriegbaum M, Liisberg KB, Wallach-Kildemoes H. Pattern of statin use changes following media coverage of its side effects Patient Preference and Adherence 2017; 11: 1151-1157. DOI: 10.2147/PPA.S133168. PubMed reference number: 28744105. Free full text.
Nielsen SF, Nordestgaard BG. Negative statin-related news stories decrease statin persistence and increase myocardial infarction and cardiovascular mortality: a nationwide prospective cohort study. European Heart Journal 2016; 37(11): 908-916. DOI: 10.1093/eurheartj/ehv641. PubMed reference number: 26643266. Free full text.
Apart from the very new injectable PCSK9 agents, ezetimibe is the only non-statin agent shown in clinical trials to reduce the risk of vascular events:
Cannon CP, Blazing MA, Giugliano RP, McCagg A, et al. Ezetimibe added to statin therapy after acute coronary syndromes. New England Journal of Medicine 2015; 372(25): 2387-2397. DOI: 10.1056/NEJMoa1410489. PubMed reference number: 26039521. Free full text.
The ACCORD study found that very intensive blood glucose control tended to slow any progression of diabetic eye disease, but it required very low blood glucose levels (e.g. HbA1c 6.0% or lower (42 mmol/mol)) that carried risks associated with hypoglycaemia. Interestingly, very good blood pressure control didn’t reduce progression. The whole portfolio (lifestyle and judicious medication) is probably more important than individual treatments:
ACCORDION Study Group. Persistent effects of intensive glycemic control on retinopathy in type 2 diabetes on the Action to Control Cardiovascular Risk in Diabetes (ACCORD) follow-on study. Diabetes Care 2016; 39(7): 1089-1100. DOI: 10.2337/dc16-0024. PubMed reference number: 27289122. Free full text.
General review of diabetic eye disease, focusing on a relatively new group of drugs, the anti-VEGF agents, which are of real value in stabilising visual function in a form of retinopathy specifically associated with Type 2 diabetes known as maculopathy or macular oedema, and which used to be treated with laser. They are also of great value in some forms of age-related macular degeneration (AMD), a very common cause of poor vision in older people. Although it is not associated with high blood glucose levels, AMD patients often have other insulin-resistant characteristics. These drugs were originally used (and still are) in cancer chemotherapy, where they reduce abnormal blood vessels in tumours. Only minute doses are needed in eye disease:
Stewart MW. Treatment of diabetic retinopathy: Recent advances and unresolved challenges World Journal of Diabetes 2016; 7(16): 333-341. DOI: 10.4239/wjd.v7.i16.333. PubMed reference number: 27625747. Free full text.
This is the reference for the final report of the Steno-2 study which showed that eight years of careful treatment of risk factors for kidney disease not only reduced the risk of kidney failure and heart attacks but bought extra years of life:
Gaede P, Oellgaard J, Carstensen B, Rossing P, et al. Years of life gained by multifactorial intervention in patients with type 2 diabetes mellitus and microalbuminuria: 21 years follow-up on the Steno-2 randomised trial Diabetologia 2016; 59(11): 2298-2307. DOI: 10.1007/s00125-016-4065-6. PubMed reference number: 27531506. Free full text.
Older Italian people had generally low blood glucose levels, and those taking sulfonylurea medication, the tablets associated with the highest risk of hypoglycaemia, were less adept at managing their everyday lives:
Abbetecola AM, Bo M, Armellini F, D’Amico F, et al. Tighter glycemic control is associated with ADL [activities of daily living] physical dependency losses in older adults using sulfonylureas or miglitinides: results from the DIMORA study. Metabolism 2015. PubMed reference number: 26318195. Abstract only.
The following is a review article by Professor Alan Sinclair and his colleagues, who pioneered clinical research on diabetes in the elderly. His view is that ideal blood glucose levels in frail elderly people should be more than 6 mmol/l and less than 15:
Abdelhafiz AH, Koay L, Sinclair AJ. The effect of frailty should be considered in the management plan of older people with type 2 diabetes. Future Science OA 2016; 2(1): FSO102. DOI: 10.4155/fsoa-2015-0016. PubMed reference number 28031949. Free full text.
Dementia, diabetes and hypoglycaemia – a particularly hazardous trio – were made worse in this German/Austrian study by an increased tendency of Type 2s with cognitive impairment to be treated with insulin, the drug by far the most likely to cause hypoglycaemia:
Prinz N, Stingl J, Dapp A, Denkinger MD, et al. High rate of hypoglycemia in 6770 type 2 patients with comorbid dementia: a multicentre cohort study on 215,932 patients from the German/Austrian diabetes registry. Diabetes Research and Clinic Practice 2016; 112: 73-81. DOI: 10.1016/j. diabres.2015.10.026. PubMed reference number: 26563590. Abstract only.
Diabetes Frail is the UK organisation specifically devoted to research and best clinical practice in older people with diabetes:
www.diabetesfrail.org (accessed 31 December 2017).
The relationship between short sleep times and high blood pressure during the night was shown in this study:
Yang H, Haack M, Gautam S, Meier-Ewert HK, Mullington JM. Repetitive exposure to shortened sleep leads to blunted slee-passociated blood pressure dipping. Journal of Hypertension 2017; 35(6): 1187-1194. DOI: 10.1097/HJH.0000000000001284. PubMed reference number: 28169885. Abstract only.
Job burnout is a significant risk factor for a wide variety of serious medical and psychological conditions, including Type 2 diabetes:
Salvagioni DAJ, Melanda FN, Mesas AE, Gonzalez AD, Gabani FL, Andrade SM. Physical, psychological and occupational consequences of job burnout: a systematic review of prospective studies. PLoS One 2017; 12(10): e0185781. DOI: 10.1371/journal.pone.0185781. PubMed reference number: 28977041. Free full text.
Intensive lifestyle intervention in the Look AHEAD trial reduced the risk of developing depression, and physical function benefited as well:
Rubin RR, Wadden TA, Bahnson JL, Blackburn GL, et al. Impact of intensive lifestyle intervention on depression and health-related quality of life in type diabetes: the Look AHEAD trial. Diabetes Care 2014; 37(6): 1544-1553. DOI: 10.2337/dc13-1928. PubMed reference number: 24855155. Free full text.
Collaborative care between specialists and general practitioners can give good results. For example, one trial focused on intensive medication management of depression, heart disease and poorly controlled Type 2 diabetes. Medical, psychological and quality of life outcomes all improved over a year:
Katon WJ, Lin EH, Von Korff M, Ciechanowski P, Ludman EJ, et al. Collaborative care for patients with depression and chronic illnesses. New England Journal of Medicine 2010; 363(27): 2611-2620. DOI: 10.1056/NEJMoa1003955. PubMed reference number: 21190455. Free full text.
In people with poorly controlled Type 1 or 2 diabetes and depression, a year of antidepressant treatment (using the drug sertraline) was more effective in helping depression than cognitive behavioural therapy (CBT), but blood glucose levels did not improve with either treatment:
Petrak F, Herpertz S, Albus C, Hermanns N, et al. Cognitive behavioural therapy versus sertraline in patients with depression and poorly controlled diabetes: the Diabetes and Depression (DAD) Study: a randomized controlled multicentre trial. Diabetes Care 2015; 38(5): 767-775. DOI: 10.2337/dc14-1599. PubMed reference number 25690005. Abstract only.
www.diabetes.co.uk (‘The global diabetes community’).