type 2 diabetes in the elderly - Europe PMC

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Journal of the Royal Society of Medicine Volume 87 October 1994

23 Asplund K, Wiholm BE, Lithner F. Glibenclamide associated hypoglycaemia: a report on 57 cases. Diabetologia 1985;24:412-17 24 Gale EAM, Dornan TL, Tattersall RB. Severely uncontrolled diabetes in the over-fifties. Diabetologia 1981;21:25-8 25 Gale EAM, Tattersall RB. Hypothermia, a complication of diabetic ketoacidosis. BMJ 1978;ii:1387-9 26 Neil HAW, Dawson HAW, Baker JE. Risk of hypothermia in elderly patients with diabetes. BMJ 1986;293:416-18 27 Abbott RD, Donahue RP, MacMahan SW, Reed DM, Yano K. Diabetes and the risk of stroke. The Honolulu heart program. J Am Med Assoc 1987;257:949-52 28 Pulsinelli WA, Levy DE, Sigsbee B, Scherer P, Plum F. Increased damage after ischaemic stroke in patients with or without established diabetes mellitus. Am J Med 1983;74:540-4 29 Petri MP, Gatling W, Petri L, Hill RD. Diabetes in the elderly - an epidemiological perspective. Pract Diabetes 1986;3:153-5 30 Klein BEK, Klein R. Ocular problems in older Americans with diabetes. Clin Geriatr Med 1990;6:827-37 31 Soler NG, Fitzgerald MG, Malins JM, Summers ROC. Retinopathy at diagnosis of diabetes, with special reference to patients under 40 years of age. BMJ 1969;3:567-9

32 Waugh NR. Amputations in diabetic patients - a review of rates, relative risks and resource use. Comm Med 1988;10:279-88 33 Perlmuter LC, Hakami MK, Hodgson-Harrington C, Ginsbert J, Katz J, Singer DE, et al. Decreased cognitive function in aging non-insulin-dependent diabetic patients. Am JMed 1984;77:1043-8 34 Reaven GM, Thompson LW, Nahum D, Haskins E. Relationship between hyperglycaemia and cognitive function in older NIDDM patients. Diabetes Care 1990;13:16-21 35 Damsgaard EM, Froland A, Green A. Use of hospital services by elderly diabetics: the Fredericia study of diabetic and fasting hyperglycaemic patients aged 60-74 years. Diabetic Med 1987;4:317-22 36 Damsgaard EM, Froland A, Holm N. Ambulatory medical care for elderly diabetics: the Fredericia survey of diabetic and fasting hyperglycaemic subjects aged 60-74 years. Diabetic Med 1987; 4:534-8 37 Damsgaard EM. Why do elderly diabetics burden the health care system more than non-diabetics. Dan Med Bull 1989;36:89-92 38 Croxson SCM, Price DE, Burden M, Jagger C, Burden AC. The mortality of elderly people with diabetes. Diabetic Med 1994;11F250-2

Tablet and insulin therapy in type 2 diabetes in the elderly

Introduction Let us consider the major therapeutic options available for the management of type 2 diabetes in the elderly. First, it is worth summarizing the aims of modern diabetic management which include: (1) prevention of symptoms of hyperglycaemia; (2) avoidance of hypoglycaemia; (3) prevention of long term vascular complications; (4) preservation of quality of life. The quality of life issue has been much neglected, but is now recognized as being very important. The mainstay of treatment of type 2 diabetes is diet. Diets, however, must be realistic - it is unreasonable to expect someone who has spent many decades eating a particular range of foods to make drastic changes to their eating habits. The recommendations for 'healthy eating' should be followed as far as possible' with the basic diet high in unrefined high fibre carbohydrate (> 50% of calorie content) and fat contributing less than 35% of calories. In newly diagnosed patients unless they are heavily symptomatic, diet alone should be prescribed for two to three months. Where the patient remains symptomatic or control is not adequate on diet alone then additional therapies need to be considered (Figure 1).

(Accepted 8 June 1994)

A H Barnett MD Professor of Diabetic Medicine, Undergraduate Centre, University of Birmingham and Birmingham Heartlands Hospital, Bordesley Green East, Birmingham B9 5SS, UK

Keywords: diabetes; elderly; oral hypoglycaemics; insulin therapy

Summary There are a range of therapeutic options available for the management of type 2 diabetes in the elderly. Diet remains the mainstay of treatment although this must be realistic. If diet alone is unsuccessful then, for most patients, short-acting sulphonylurea agents are the treatment of choice. Second line agents include the biguanide, metformin, or an a-glucosidase inhibitor. A significant proportion of type 2 diabetic patients will, however, eventually require insulin to alleviate symptoms of poor control and improve glycaemia. In this article I discuss the therapeutic options available for diabetic management in the elderly, with particular emphasis on the pros and cons of insulin treatment.

Tablet treatment There are now a range of tablet therapies available for management of type 2 diabetes.

Newly diagnosed patient 2-3 months on DIET alone

May represent several months to several years 'I Control adequate-No-Re-assess diet-3 months-Control adequate-No-Is diet optimal?-Control adequate-No-Commence I Increase or twice daily Consider short acting Yes Yes Yes SULPHONYLUREA combine insulin I or oral agents Continue Continue Continue METFORMIN if very obese diet + tablet(s) diet + tablets diet alone (other options include _

2-glucosidase inhibitor or guar gum)

Figure 1. Therapy of type 2 diabetes in the elderly

_

Paper read to Section of Geriatrics & Gerontology, 29 September 1993


Sulphonylureas The hypoglycaemic effect of sulphonamides was first noted in the 1940s and by the mid-1950s sulphonylurea agents were developed for their specific hypoglycaemic effect. They are thought to work by stimulating insulin release from the ,3-cells of the pancreas2 and by increasing insulin receptor binding sites and perhaps decreasing gluconeogenesis3. For practical purposes sulphonylureas can be divided into two major groups long acting and short acting. The long-acting drugs include chlorpropamide and glibenclamide and the short-acting drugs gliclazide, glipizide, tolbutamide and various others. The longacting drugs are best avoided in the elderly population, since they are more likely to provoke severe hypoglycaemia which has a significant morbidity and some mortality4'5. Other, less common, side-effects include skin rashes, gastrointestinal disturbance, blood dyscrasias and toxic hepatitis. Sulphonylureas are generally efficacious in most type 2 diabetics, particularly in the first two years after diagnosis and should be used as first line agents except where the patient is grossly obese when a biguanide may be preferable. -

Biguanides They are unrelated to sulphonylureas the only one still in use is metformin. Their action is not dependent on functional pancreatic ,B-cells and they are thought to work by increasing glucose uptake by peripheral tissues, increasing insulin sensitivity and reducing hepatic gluconeogenesis6'7. They should normally be used as second line agents in combination with sulphonylureas, except where the patient is grossly obese, when they can be used as first line treatment. Metformin has a high incidence of side-effects such as anorexia, dyspepsia and diarrhoea and it is always advisable to start with a relatively low dose. Indeed, I rarely go beyond 500 mg twice a day, although the manufacturers suggest that the maximum dose is at least double this. The only serious, but very rare, side-effect is lactic acidosis8. It was more common with the biguanide phenformin which is no longer used. Lactic acidosis is only normally seen in association with hepatic or renal impairment or cardiac failure. For this reason some authorities recommend not using metformin in the over 70 age group. Certainly, liver and hepatic function should be checked in elderly patients before starting the drug. -

Other agents These include compounds such as guar gum, which has a very high fibre content, and reduces absorption of carbohydrate and consequently hyperglycaemia. It has only a limited clinical effect and a common sideeffect is flatulence. The a-glucosidase inhibitors (e.g. acarbose) have also recently been introduced to the UK market. These act as enzyme inhibitors reducing the breakdown of complex carbohydrate in the gut and therefore reducing their absorption9. This results in lowering of postprandial hyperglycaemia and a smoothing effect on fluctuations in the daily blood glucose profile. They have no stimulatory action on the pancreas and should not, therefore, cause hypoglycaemia. Acarbose is normally given in a three times a day dosage with the first mouthful of food at each meal. Flatulence may be a problem.

Insulin in the management of the elderly type 2 diabetic patient The natural history of type 2 diabetes is such that most patients will be adequately controlled on diet±tablets for several years, but approximately 50% will eventually end up on insulin. The indications for insulin treatment are: (1) to cover acute illness/operations; (2) the prevention of microvascular complications; and (3) poor diabetic control±symptoms. Clearly, during acute situations insulin may be necessary to preserve adequate diabetic control, but the patient can usually then come off insulin once the episode is over. More controversial, is whether insulin will help prevent or retard the long-term vascular complications. There is a wealth of epidemiological data which suggest that the better the control in the earlier years of diabetes the less the likelihood of complications later on10. This data has been supported by prospective studies1l1'4 and, in particular, the recently completed Diabetes Control and Complications Trial in the US15. The latter trial looked specifically at type 1 diabetics but there is no reason to think that the same would not apply for type 2 patients. There is, therefore, an increasing body of evidence which suggests that we should be trying to achieve as good diabetic control as is realistic. The age ofthe patient is becoming less relevant as many elderly diabetics are now surviving long enough to develop complications and indeed some have them at diagnosis. The other main indication for insulin treatment is persistent poor control with or without typical symptoms such as thirst, polyuria and vulval pruritus. Close questioning of poorly controlled patients who deny symptoms often reveals that they are less than well with tiredness, lack of energy, reduced feeling of well-being and difficulty coping with day to day life. This has been termed the 'hyperglycaemic malaise' syndrome and is now well recognized16. This group of patients often benefits from insulin treatment. In a recent study'7 of 15 elderly type 2 diabetics with fasting blood glucose >9 mmol/l all claimed to be asymptomatic but agreed to try insulin. Over the 8 month period of the study there was a significant fall in fasting blood glucose and HbA1. At the end of the study only two patients wanted to resume tablets. The author concluded that: asymptomatic hyperglycaemia in elderly patients is often associated with reduced well-being and a trial of insulin may be indicated. The insulin normally has to be given by twice daily injection and ideally monitoring should be with home blood glucose testing - most patients (even the elderly) adapt well.

Arguments for and against insulin treatment These are summarized (Table 1). There is no doubt that many patients feel better once they start insulin, Table 1. Pros and cons of insulin treatment Pros

Cons

Patients often 'feel better' Improved diabetic control Weight gain in those who are underweight ?Prevention/amelioration of microangiopathy

Fear of injections Hypoglycaemia Weight gain in obese patients

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even if they do not have dramatically improved diabetic control17"18. There is also the possibility that improved control may be associated with reduction of risk for diabetic microvascular disease. The major drawbacks to insulin treatment include fear of injections. This is usually easily overcome with careful counselling, particularly with the help of the diabetes specialist nurse. The other major concern is hypoglycaemia but this is not usually a serious problem in most type 2 diabetics, particularly since we are not usually aiming for quite the fine control that might be required for younger type 1 patients. It is also worth remembering that sulphonylureas can cause severe and devastating hypoglycaemia! There have also been concerns that insulin therapy might exacerbate insulin resistance, but in fact enhanced insulin sensitivity is common after a period of insulin therapy'9. There are additional theoretical fears that hyperinsulinaemia might cause accelerated atherogenesis and even hypertension but there is no proof of this. Indeed, the reality of hyperglycaemia accelerating complications of diabetes and causing ill health outweighs these theoretical risks.

Quality of life issues There has been a reluctance to advise type 2 diabetics, particularly the elderly, to go onto insulin largely because of the mistaken belief that we are in some way preserving the patient's quality of life by withholding injections. As stated, however, many patients feel better on insulin and most do not want to go back onto tablets. Even elderly patients tend to cope well with injections. Life has also been made easier by the advent offixed mixtures of insulin, home blood glucose monitoring, better education and insulin 'pens'. There is now a wide range of pens and insulin available in cartridge form20. In a recent study the overwhelming conclusion was that pens are easy to use by a wide range of patients and are preferable to syringes and needles in over 90% of cases. Half of those studied noted an improvement in quality of life2'. What regime? The ideal insulin regime should have low risk of hypoglycaemia, should be simple to use and give satisfactory glycaemic control. For most patients, particularly the elderly, the best available regime is either twice daily isophane (e.g. Humulin I, Eli Lilly, or Insulatard, Novo Nordisk) or a fixed mixture of isophane and soluble insulin (e.g. Humulin M3, Eli Lilly, or Mixtard, Novo Nordisk). In a recent study of elderly patients, twice daily intermediate acting insulin regimes were associated with a very low frequency of hypoglycaemia and a significant improvement in control22. There is rarely a place for once daily long-acting insulin, as glycaemic control is unpredictable with wide swings in blood glucose and increased susceptibility to hypoglycaemia compared with twice daily injections. In summary, insulin is an appropriate therapeutic option for type 2 diabetes. The initiation of insulin therapy is often too long delayed and patients have suffered as a result. Most patients cope well and many have an improved quality of life since starting insulin. Conclusions The aims of modern diabetic management are clear but not always fulfilled. There are a range of treatment options for the management of diabetes in

elderly patients. Diet remains the mainstay of treatment with the option of adding in a range of tablet therapies which will adequately control most diabetics for at least a few years after diagnosis. For those patients who are inadequately controlled insulin is a practical alternative therapy. Insulin treatment is too often withheld because of the mistaken belief that the physician is in some way preserving the quality of life of the patient. In practise, many of these patients are unwell, but do not necessarily have the typical symptoms of diabetes. Most will benefit from insulin treatment. The advent of highly purified insulins, fixed mixtures, home blood glucose monitoring, better educational facilities and new delivery devices, such as insulin pens, has improved the quality of life for many diabetic patients and hopefully this process will continue. References 1 Mann JI, Lewis-Barned NJ. Dietary management of diabetes mellitus in Europe and North America. In: Alberti KGMM, Defronzo RA, Keen H, Zimmet P, eds. International Textbook of Diabetes Mellitus. Chichester: John Wiley and Sons, 1992:685-700 2 Hosker JP, Burnett MA, Davies EG, Turner RC. Sulphonylurea therapy doubles beta-cell response to glucose in type 2 diabetic patients. Diabetologia 1985;28:809-14 3 Feinglos MN, Leboritz HE. Sulphonylureas increase the number of insulin receptors. Nature 1978;275:184-5 4 Asplund K, Wilholm B, Lithner F. Glibenclamide associated hypoglycaemia: a report on 57 cases. Diabetologia 1983;24:412-17 5 Campbell IW. Metformin and the sulphonylureas: the comparative risks. Horm Metab Res Suppl 1985;15:105-11 6 Prager R, Schernthaner G, Graf H. Effect of metformin on peripheral insulin sensitivity in non-insulin dependent diabetes mellitus. Diabete Metab 1986;12:346-50 7 Gawler DJ, Milligan G, Houslay MD. Treatment of streptozotocin diabetic rats with metformin restores the ability of insulin to inhibit adenylate cyclase activity. Biochem J 1988;249:537-42 8 Ryder RE. Lactic acidosis: high dose or low-dose bicarbonate therapy. Diabetes Care 1984;7:99-102 9 Crentzfeld W (ed.). Proceedings Second International Symposium, Acarbose, Berlin (1987). Berlin: Springer Verlag, 1988 10 Tchobroutsky G. Relation of diabetic control to development of microvascular complications. Diabetologia 1978;15:143-52 11 Lauritzen T, Larsen HW, Deckert T, Steno Study Group. Two years experience with continuous subcutaneous insulin infusion in relation to retinopathy and neuropathy. Diabetes 1985; 34(suppl 3):74-9 12 The Kroc Collaborative Study Group. Diabetic retinopathy after two years of intensified insulin treatment. J Am Med Assoc

1988;260:37-41 13 Brinchmann-Hansen 0, Dahl-Jorgensen K, Sandrik L, Hanssen KF. Blood glucose concentrations and progression of diabetic retinopathy: the seven years results of the Oslo study. BMJ

1992;304:19-22 14 Reichard P, Berglund B, Britz A, Cars I, Nilsson BY, Rosenqvist U. Intensified conventional insulin retards the microvascular complications of insulin-dependent diabetes (IDDM): the Stockholm Diabetes Intervention Study (SDIS) after 5 years. J Intern Med 1991;230:101-8 15 Diabetes Control and Complications Trial Research Group. The effect on intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 1993;329:977-86 16 Taylor R. Use of insulin in non-insulin dependent diabetes.

Diabetes Rev 1992;1:9-11 17 Berger W. Insulin therapy in the elderly Type 2 diabetic patient. Diabetes Res Clin Pract Suppl 1988;1:24-8 18 Peacock I, Tattersall RB. The difficult choice of treatment for poorly controlled maturity onset diabetes: tablets or insulin? BMJ 1984;288:1956-9 19 Genuth S. Insulin use in NIDDM. Diabetes Care 1990;13:1240-64 20 Rewe BR. Insulin pen delivery systems. Diabetes Rev 1992;1:2-4 21 Rowe BR, Pizzey M, Barnett AH. A clinical evaluation of the B-D (Becton-Dickinson) pen as a delivery device for human insulin. Pract Diabetes 1992;9:138-9 22 Elgrably F, Costagliola D, Chwalow AJ, Varenne P, Slama G, Tchobroutsky G, et al. Initiation of insulin treatment after 70 years of age: patient status two years later. Diabet Med 1991;8:773-7 (Accepted 8 June 1994)