The diabetes year in review

The New Year, a time when many of us make at least one resolution, is an opportunity to look back as well as forward at important developments in diabetes care that could improve the outlook for patients with either type 1 or type 2 diabetes

Diabetes is a significant cause of morbidity and mortality. It carries a huge burden of cardiovascular disease – both macrovascular and microvascular – and is one of the most important causes of myocardial infarction, stroke, peripheral arterial disease, end stage renal disease, amputations and blindness. Yet many of these complications could be avoided by careful management of the ‘terrible triad’ of hyperglycaemia, hypertension and dyslipidaemia.¹

The start of a new year is a perfect opportunity to look at some of the recent developments in diabetes care, both in type 1 and type 2, and take out our crystal ball to predict changes that may be on the horizon for the year ahead. There is also a wish list for future diabetes care.

THE STATE OF THE NATION

The annual State of the Nation report, published at the end of 2013, made for somewhat depressing reading.² It highlighted that diabetes uses a significant proportion of NHS resources – almost 10% of NHS spending, in fact – and continues to be a major challenge. Bearing in mind that 90% of diabetes is type 2, this means that we are spending huge amounts of time and money treating a disease which is largely preventable. Most of the money spent on diabetes is spent on treating the complications of the condition, both macrovascular (strokes, peripheral artery disease and myocardial infarction) and microvascular (diabetic nephropathy leading to end stage renal disease, retinopathy leading to blindness, and neuropathy leading to amputations).

A disturbing aspect of the report is that it revealed that people who live in the best-performing Clinical Commissioning Group (CCG) areas are four times more likely to be given the vital health checks that improve outcomes for people with diabetes than those living in the worst-performing areas. Compounding this, the report shows that less than one in 20 people with diabetes is being offered diabetes education, care planning and support for self-management.

This situation is completely unacceptable and our current approach smacks of closing the stable door after the horse has bolted. We need to invest more in the prevention and management of diabetes so that these life-changing, life-limiting, expensive, long-term complications are avoided and we end up spending less on mopping up the fall-out of sub-optimal care and management.

CARE PROVISION IN 2014

With the findings of The State of the Nation report in mind, it is clear that care planning, which focuses on patient centred care with involvement of the individual throughout, is essential. The publication of a diabetes care checklist from Diabetes UK can only help in this aim.³ Fifteen key areas, which should be fulfilled by clinicians for people with diabetes, are listed and should allow both patients and clinicians to ensure that good quality care is being delivered. A useful tool which highlights the standard of care being offered by each CCG and compares it with other CCGs is Diabetes Watch from Diabetes UK.⁴ For more specific practice-based data, the latest report from Public Health England makes essential reading.⁵

The statistics for type 1 diabetes are of no less concern. A report from the Health and Social Care Information Centre published in October showed that young people under the age of 40 with type 1 diabetes were even less likely than older people or those with type 2 diabetes to be offered care that could reduce their risk of long-term complications.⁶

Overall, these reports highlight that there is still a great deal of work that needs to be done in diabetes care.

TREATING DIABETES AND REDUCING RISK

Evidence-based guidance on treating diabetes is an essential component of improving care. At the time of writing the 2014 update of the National Institute for Care and Health Excellence’s (NICE) guidelines on treatments for type 2 diabetes was due for publication. The last updates were in 2008 and 2009.7,8 Since then there has been a veritable smorgasbord of new therapies developed, offering a wider scope for treating hyperglycaemia without the significant side effects that can be seen with older drugs, particularly sulfonylureas (SUs).⁹

The NICE update, when it is published, will provide an excellent opportunity to recognise the importance of using drug treatments alongside lifestyle interventions to reduce future risk of complications, but also to minimise the risk of complications from the drug treatments themselves. Clinicians should always consider this risk when deciding ‘what next after metformin’. The updated guidelines will, hopefully, reflect the approach of the American Diabetes Association/European Association for the Study of Diabetes (ADA/EASD) guidelines.¹⁰ These give much more weight to the concept of tailoring treatment choices to the individual and giving patients a real opportunity to make decisions about their treatment through fully informed consent – or dissent.

NEW DRUGS

The big story in diabetes medication in 2014 was the increasing use of a relatively new class of drugs called sodium-glucose co-transporter 2 (SGLT2) inhibitors. SGLT2 inhibitors block the reabsorption of glucose into the body so that it is excreted in the urine instead. As a result, the blood glucose levels fall, and the loss of around 250 calories worth of sugar each day can also lead to weight loss. The glycosuria produced by SGLT2 inhibitors can lead to an increase in genitourinary infections, such as thrush and urinary tract infections, but in general these infections were found to be relatively mild, occurred in the first year of treatment and rarely recurred.¹¹

There are three SGLT2 inhibitors currently available:

• Dapagliflozin (10 mg once daily, 5 mg in hepatic impairment)
• Canagliflozin (100 mg increasing to 300 mg once daily)
• Empagliflozin (10-25mg daily).

These can be used as monotherapy or in combination with most other hypoglycaemic agents, including insulin.

Last year also saw the launch of a new dual therapy combining metformin and dapagliflozin, and new additions to the dipeptidyl peptidase-4 (DPP4) inhibitor class of oral hypoglycaemic agents. All of these drugs, along with other newer therapies such as glucagon-like peptide-1s (GLP1s) offer opportunities to reduce blood glucose with almost no risk of hypoglycaemia. These drugs also have the advantage of being weight neutral, and in the case of the SGLT2 inhibitors or GPL1s of facilitating weight loss.

The electronic medicines compendium website (https://www.medicines.org.uk/emc) has information on these drugs and the rest of the range of products available to treat abnormal blood glucose levels.

These newer options may take some time to appear on local formularies, many of which still default to the somewhat outdated pathway of sulfonylureas and insulin after metformin. However, clinicians should be aware of all the treatments available in order to ensure that patients have equal access to newer drugs along with the older more established therapies. It should be remembered that although formularies may appear to make treatment decisions easier, guidelines do not replace clinical decision making. Too often formularies are dictated by drug acquisition costs rather than by considering the holistic cost and value of the drugs, including the cost to the NHS of treating hypoglycaemia and the potentially expensive business of home blood glucose testing. It can be a challenge, but clinicians should ensure that patients are active partners in decision making when it comes to drugs, behaviour change and self-monitoring and to do this both the clinician and the patient will need to know of the range of options available.

NEW APPROACHES TO DYSLIPIDAEMIA

In July last year NICE published its latest guidelines on managing lipids.¹² The guidance included advice for implementing lipid lowering treatment in people with both type 1 and type 2 diabetes. The focus is now on non-HDL cholesterol, rather than LDL cholesterol and the aim is to reduce non-HDL cholesterol by 40%.

The message with type 1 diabetes is that most people over 40 or who have had diabetes for more than 10 years will benefit from a statin – specifically atorvastatin 20mg, titrated as required – unless there are contraindications. In type 2 diabetes, the advice is that 10 year cardiovascular risk should be calculated using Qrisk and if the score is 10% or more atorvastatin 20mg should also be initiated.

The latest guidelines reiterate that statins and ezetimibe are effective lipid lowering therapies. The IMPROVE-IT trial, awaiting publication, reported in November last year. It demonstrated that lowering LDL cholesterol using a statin and ezetimibe reduced cardiovascular risk in high risk patients.¹³ Other therapies (e.g. fibrates, nicotinic acid, bile acid sequestrants) continue to be deemed by NICE as unsuitable lipid lowering agents.

TESTOSTERONE, DIABETES AND CARDIOACULAR RISK

The link between low testosterone levels and the development of metabolic syndrome and diabetes has been known for some time.¹⁴ Research published last year, however, went a step further towards increasing awareness of the risk of low testosterone levels in men who have already been diagnosed with diabetes.¹⁵

In this study, an increased risk of cardiovascular complications was identified in men with diabetes and low testosterone. The study confirmed that this combination of conditions resulted in a six-fold increase in carotid artery atheroma in comparison to men with normal testosterone levels. Although it is not clear whether treating these low testosterone levels as a means of reducing cardiovascular risk would work, it does suggest that in patients known to have low testosterone levels we need to be especially aggressive when managing other cardiovascular risk factors.

BARIATRIC SURGERY

At the end of November 2014 NICE updated its guidance on weight loss surgery.¹⁶ It recommends that all patients with a BMI of 35kg/m2 or over and recent-onset type 2 diabetes should be offered an expedited assessment for bariatric surgery. They should also have tried and failed to achieve weight loss by all other appropriate, non-surgical methods. NICE also states that surgery is beneficial for those with recent-onset, poorly controlled diabetes and a BMI of 30-34kg/m2.9

The level at which body fat becomes a health risk varies between ethnic groups. Asian people are known to be particularly vulnerable to the complications of diabetes. NICE therefore recommend a lower BMI threshold for referral of people of Asian origin with recent-onset type 2 diabetes.

The subject of bariatric surgery for obesity often generates controversy in the general public – why should my tax money be spent on people who overeat and don’t have the willpower to lose weight by dieting! However, it appears that the health benefits of bariatric surgery for people with type 2 diabetes are greater than we would have expected. The surgery itself, by neuro-endocrine mechanisms that are, as yet, poorly understood, can lead to improvements in glycaemic control and, in a significant number of cases, complete remission of type 2 diabetes independently of the amount of weight lost.¹⁷ It has been estimated that the initial, short-term costs of surgery could be repaid in cost-savings on drug expenditure and treating the complications of diabetes within 2-3 years. The long-term cost-savings for the NHS could be considerable.

Further information about when to offer surgery is available at: http://pathways.nice.org.uk/pathways/obesity#path=view%3A/pathways/obesity/surgery-for-obese-adults.xml&content=view-node%3Anodes-when-to-offer-surgery

CRYSTAL BALL GAZING

Looking to the future, one of the biggest and most exciting breakthroughs in type 1 diabetes research was announced this year. Doug Melton, who has two children with type 1 diabetes, has been undertaking research into a cure for diabetes for over 20 years. His latest findings suggest that it may be possible to use stem cells to manufacture human insulin-producing beta cells. These could then be transplanted into people with type 1 diabetes to enable them to produce insulin.¹⁸ The research has been carried out in primates and they were all continuing to produce insulin from their newly implanted and fully functioning beta cells months after the transplant had been carried out.

In theory this ground-breaking research could mean that injecting insulin could become a thing of the past. It has been hailed as one of the most important scientific breakthroughs since the discovery of antibiotics.

A DIABETES WISH LIST

Number one on my diabetes wish list would be to see the stem-cell research coming to fruition soon. For people with type 1 diabetes, and for those of us with friends and relatives with type 1, this must surely be the Holy Grail – a permanent cure.

For those with, or at risk of type 2 diabetes, the link with obesity cannot be ignored and so a ‘cure’ for obesity would be high up on the list too. In spite of an array of over the counter ‘treatments’, orlistat and the use of bariatric surgery, the fact remains that obesity levels are increasing in the UK and more and more adults, and even children, are overweight or obese.

Lifestyle interventions remain the most important approaches to ‘curing’ and preventing type 2 diabetes. Anything which helps people to eat more healthily and take more exercise would help. The concept of a ‘sugar tax’ or ‘fat tax’ has been mooted, but without success. The food industry and government have competing interests and contradictory aims and objectives – returning a profit, collecting taxes and paying for the NHS – making for indistinct battle lines and complicating the fight to develop sensible, workable and effective policies. Nonetheless, comparisons can be easily made with the tobacco industry in respect of the potential harm caused, particularly by sugar.

SUMMARY

For type 1 diabetes a cure may be within reach – an exciting prospect which will liberate many from the drudgery of controlled eating, insulin dosing and blood glucose monitoring. For type 2, there has been a lot of discussion this year about the epidemic of diabetes which is riding the crest of the obesity wave.

Quality of care remains variable and largely sub-optimal and we need to stop and ask why this is. Health care solutions need to start focusing more effectively on prevention and early, proactive management rather than on simply picking up the pieces in terms of complications. We need a new and dynamic approach to helping people to implement behaviour change and make better choices regarding diet and activity. In the meantime, the focus will remain on effective treatment of diabetes, addressing the deadly triad of hyperglycaemia, dyslipidaemia and hypertension using drugs which optimise outcomes and minimise risk and which are tailored to each individual.

REFERENCES

1. Gaede P, Lund-Andersen H, Parving HH, Pedersen O. Effect of a multifactorial intervention on mortality in type 2 diabetes. New England Journal of Medicine 2008; 358(6):580–91

2. Diabetes UK. State of the Nation report. 2013 http://www.diabetes.org.uk/Documents/About%20Us/What%20we%20say/0160b-state-nation-2013-england-1213.pdf

3. Diabetes UK. 15 Healthcare Essentials. 2014 http://www.diabetes.org.uk/Guide-to-diabetes/Monitoring/15-healthcare-essentials/

4. Diabetes UK. Diabetes Watch. 2014 http://diabeteswatch.diabetes.org.uk/?_ga=1.75537109.1957280442.1393093944

5. Public Health England. Healthier Lives: Diabetes. 2014 http://healthierlives.phe.org.uk/

6. Health and Social Care Information Centre. National Diabetes Audit - 2012-2013: Report 1, Care Processes and Treatment Targets. 2014 http://www.hscic.gov.uk/catalogue/PUB14970

7. NICE. Type 2 diabetes. Clinical Guideline 66. 2008 http://www.nice.org.uk/guidance/cg66

8. NICE. The management of type 2 diabetes. Clinical Guideline 87. 2009 https://www.nice.org.uk/guidance/cg87

9. Phung OJ, Schwartzman E, Allen RW, et al. Sulphonylureas and risk of cardiovascular disease: Systematic review and meta-analysis. Diabetic Medicine 2013; 30(10):1160-71

10. Inzucchi SE, Bergenstal RM, Buse JB, et al. Management of hyperglycemia in type 2 diabetes: a patient-centered approach: position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care 2012;35(6): 1364–79

11. Bailey CJ, Gross JL, Pieters A, Bastien A, List JF. Effect of dapagliflozin in patients with type 2 diabetes who have inadequate glycaemic control with metformin: a randomised, double-blind, placebo-controlled trial Lancet 2010; 375: 2223–33

12. NICE. Lipid modification: cardiovascular risk assessment and the modification of blood lipids for the primary and secondary prevention of cardiovascular disease. Clinical Guideline 181. 2014 https://www.nice.org.uk/guidance/cg181

13. Kumbhani DJ. Trial report IMPROVE-IT. Cardiosource. 2014 Available at: http://www.cardiosource.org/science-and-quality/clinical-trials/i/improve-it.aspx?w_nav=RI

14. Laaksonen DE, Niskanen L, Punnonen K, et al. Testosterone and sex hormone–binding globulin predict the metabolic syndrome and diabetes in middle-aged men. Diabetes Care 2004;27: 5 pp1036-1041

15. Farias JM, Tinetti M, Khoury M, Umpierrez GE. Low testosterone concentration and atherosclerotic disease markers in male patients with type 2 diabetes. Journal of Clinical Endocrinology and Metabolism 2014 Available from: http://press.endocrine.org/doi/pdf/10.1210/jc.2014-2585

16. NICE. Obesity: identification, assessment and management of overweight and obesity in children, young people and adults. Clinical Guideline 189. 2014 http://www.nice.org.uk/guidance/CG189

17. Pournaras DJ, Osbourne A, Hawkins SC, et al. Remission of type 2 diabetes after gastric bypass and banding: mechanisms and 2 year outcomes. Annals of Surgery 2010;252(60):966-71

18. Harvard Stem Cell Institute. From stem cells to billions of human insulin-producing cells. 2014 http://hsci.harvard.edu/news/stem-cells-billions-human-insulin-producing-cells