The incidence of diabetes, in particular type 2 diabetes, is skyrocketing. This is mainly attributed to ageing populations, increased obesity and Westernisation of lifestyle. The estimated diabetes prevalence worldwide for 2011 was 366 million and it is expected to affect 552 million people by 2030. By 2025, it is estimated that five million people will have diabetes in the UK.1
The impact of type 2 diabetes on patients is astronomical including microvascular and macrovascular complications resulting in high morbidity and mortality. Cardiovascular disease is a major cause of death in people with diabetes, accounting for 44% of fatalities in type 1 diabetes and 52% of fatalities in type 2 diabetes.2 This includes heart disease, stroke, and accelerated atherosclerosis resulting in peripheral vascular disease. It has been suggested that people with type 2 diabetes have a two-fold increased risk of stroke in the first five years of diagnosis of diabetes compared with general populations.3 Diabetes is also the single most common cause of end stage renal failure. Almost one in three people with type 2 diabetes develops overt kidney disease accounting in 11% of deaths.4
Diabetes is the leading cause of blindness in the UK. Within 20 years of diagnosis nearly all people with type 1 and two-thirds of people with type 2 diabetes have some degree of retinopathy. Good glycaemic control clearly reduces the risk of developing retinopathy and visual loss.
Glycaemic management issues in older diabetic patients
Older people are a heterogeneous population ranging from independently living patients to those living in care homes with a complex medical and social background. Thus older adults with diabetes can be fit and healthy or frail with multiple comorbidities and functional disabilities.
The management of type 2 diabetes is complex. With the wide array of pharmacological treatments available clinicians are often faced with a treatment dilemma especially in older people.
The overall goal of diabetes management in older adults is to treat hyperglycaemia, other risk factors and co-existing medical conditions. However, at the same time avoidance of hypoglycaemia, hypotension, and drug interactions due to polypharmacy are equally important, as it influences their ability to perform self-management.
There is strong evidence that intensive glucose lowering therapy have no benefits on cardiovascular outcomes.4-5 The UKPDS4 (United Kingdom Prospective Diabetes Study) tested the effect of more versus less intensive glycaemic control in middle-aged patients (mean age, 53 years) with newly diagnosed type 2 diabetes mellitus. The results, similar to those of the DCCT6 (Diabetes Control and Complications Trial) in patients with type 1 diabetes mellitus, demonstrated that intensive therapy delayed the onset and reduced the progression of albuminuria and retinopathy but did not decrease the risk for myocardial infarction (MI). A 10-year observational follow-up of the DCCT6 found a reduced rate of MI, despite haemoglobin A1c (HbA1c) values that converged at approximately 8.0% after two years. It is therefore very important to treat patients as individuals according to their background, comorbid and psychosocioeconomic status.
In young patients with relatively recent onset of type 2 diabetes mellitus, strict glycaemic control aimed at a near-normal (or normal) glycaemic target range should be implemented whenever safe and possible, with the goal of preventing microvascular and macrovascular complications over the life span. However, in older persons with established type 2 diabetes mellitus of long duration and evidence of or risk factors for CVD, a more relaxed target range can be considered. The proposed glycaemic target range should then be adjusted on the basis of the patient's psychosocioeconomic context.
Drug therapy in management of type 2 diabetes
Low caloric intake, increased physical activity, weight loss, and patient education are all an integral part of the management of type 2 diabetes in older people. Life style modifications in older people have almost the same benefit as in younger patients. The Diabetes Prevention Program (>60 years of age at baseline) had the greatest improvement in glycaemia over time, related in part to better adherence to the lifestyle program, compared with the younger age groups.7 This data suggest that older persons can respond well to lifestyle programmes. Therefore, all elderly patients with diabetes should receive a medical nutrition evaluation.
The following are the options that should be considered in elderly patients when medical therapy is unavoidable.
Metformin is one of the first tier medications which should be offered to diabetic patients.8 However, any contraindications (severe cardiac failure, renal impairment ie. creatinine 150 micromole/litre or the eGFR is below 30ml/minute/1.73 m2) should be carefully ruled out before starting therapy with metformin. Patients should be educated about common side effects of GI upset and the dose should be built up slowly over a few weeks. Patients who are intolerant to normal metformin should be offered a trial of extended absorption metformin before withdrawing the treatment all together. It is an excellent choice in older patients because of no risk of hypoglycaemia and help in weight loss.
Patients who are unable to take metformin because of contraindication or intolerance to therapy can be tried on short acting sulfonylurea like glipizide or gliclazide. Risk of hypoglycaemia can be a limiting factor especially with long acting sulfonylurea. Burge MR9 et al in a small study of 52 patients found that there is no significant increase in the episode of hypoglycaemia in older people treated with sulfonylurea.
The thiazolidinediones improve insulin resistance. They may also increase insulin secretion in response to glucose, at least in patients with impaired glucose tolerance.10 The thiazolidinediones may be considered for some older patients, particularly those with lower initial HbA1C values, if there are specific contraindications to sulfonylureas or if they are not able or willing to consider insulin. NICE advocates using thiazolidinediones as a second line or third line drug with metformin, sulfonylurea or insulin.11 They can be given to patients who have impaired renal function, are well tolerated in older adults, and do not cause hypoglycaemia. However, thiazolidinediones should not be used in patients with class III or IV heart failure. In addition, concerns regarding fluid retention, congestive heart failure, MI, and fractures limit their usefulness, particularly in the elderly.
Dipeptidyl peptidase IV (DPP-IV)
Dipeptidyl peptidase IV (DPP-IV) is a ubiquitous enzyme that deactivates a variety of other bioactive peptides, including glucagon-like peptide-1 (GLP-1) and glucose dependent insulinotropic polypeptide (GIP); therefore, its inhibition could potentially affect glucose regulation through multiple effects. DPP-IV inhibitors have no risk of hypoglycaemia and are weight-neutral, when used as monotherapy, and therefore may be attractive agents to use in the elderly. However, the long-term safety with this class of drug has not been established, and they are relatively expensive. The dose of DPP-IV inhibitors should be adjusted in patients with renal insufficiency.
The GLP1 analogues are incretin effect based agents available for use as monotherapy as an adjunct to diet and exercise or in combination with oral agents in adults with type 2 diabetes. Exenatide is administered twice daily and liraglutide once daily by subcutaneous injection. There is no risk of hypoglycaemia with the use of GLP-1 analogues alone. Both drugs are associated with significant reduction in weight. The most common adverse events are nausea, vomiting, and diarrhoea, occurring in 10 to 40% of treated patients. They are usually started under specialist supervision and should not be used in people with chronic renal failure
(eGFR < 30).
With the availability of long-acting insulins, it has become easier to use once daily long-acting insulin as monotherapy or as added to oral hypoglycaemic medications in older patients who have suboptimal glycaemic control. Patients may wrongly assume that their symptoms of fatigue are due to "old age" rather than hyperglycaemia. However, in many older patients, quality of life improves substantially when they take one or two daily doses of intermediate- or long-acting insulin. The risk of severe hypoglycaemia associated with insulin increases with age.12 Initiation of insulin in elderly type 2 diabetic patients should be done with the involvement of a multidisciplinary team. A complete geriatric assessment should be performed first to assure that patients can comply with their regimens and to identify potential complicating factors.
In this article we have tried to focus on the evidence available on the treatment of hyperglycaemia in older patients but also the importance of the treating the cardiovascular risk factors ie. hypertension, hyperlipidaemia, and smoking cessation is equally important. These co-existing risk factors should be aggressively treated with life-style modifications and pharmacological therapy.
The management of older adults with type 2 diabetes requires careful consideration of the effects that advancing age and changes in health status
can have on the competing risks and benefits of therapeutic interventions.
In summary, the glycaemic target range for patients with type 2 diabetes mellitus should be individualised according to age; stage of disease, both in terms of duration and presence of macro- and microvascular complications; and propensity for hypoglycaemia. In addition, careful consideration must be given to each patient's capacities, desires, and values, as well as their living situation, support systems, cognitive status, overall prognosis, and life expectancy. In nearly all circumstances, the patient should be an active participant in setting goals. Finally, glycaemic targets should not be viewed as fixed goals; they should be flexible and be adapted to changes in the patient's health and living conditions.8
Conflict of interest: none declared
1. Figures based on AHPO diabetes prevalence model: http://bit.ly/aphodiabetes
2. Morrish NJ, Wang SL, Stevens LK et al. Mortality and causes of death in the WHO multinational study of vascular disease in diabetes. Diabetologia 2001; 44 suppl 2; s14-s21
3. Emerging Risk Factors Collaboration (2010). Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies. Lancet 2010; 375 (9733); 2215-22
4. UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 1998; 352: 837-53
5. Chew EY, Ambrosius WT, Davis MD, et al; ACCORD Study Group, ACCORD Eye Study Group. Effects of medical therapies on retinopathy progression in type 2 diabetes. N Engl J Med 2010; 363: 233-44
6. The Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of longterm complications in insulin-dependent diabetes mellitus. N Engl J Med 1993; 329: 977-86
7. Diabetes Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 2002; 346(6): 393
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9. Burge MR, Schmitz-Fiorentino K, Fischette C, et al. A prospective trial of risk factors for sulfonylurea-induced hypoglycemia in type 2 diabetes mellitus. JAMA 1998; 279(2): 137
10. Cavaghan MK, Ehrmann DA, Byrne MM, Polonsky KS, Treatment with the oral antidiabetic agent troglitazone improves beta cell responses to glucose in subjects with impaired glucose tolerance. J Clin Invest 1997; 100(3): 530
11. CG66 Type 2 diabetes: full guideline
12. Shorr RI, Ray WA, Daugherty JR, Griffin MR: Incidence and risk factors for serious hypoglycemia in older persons using insulin or sulfonylureas. Arch Intern Med 1997; 157: 1681-86