Role of Education

A successful insulin management requires actively applied systems of patient education. The aim of education and training is to provide adequate information in a simple form suitable to the ability of the subject, in order to allow the diabetic patients to develop the required knowledge to self-manage their disease and to ensure an optimal and appropriate use of insulin therapy (and other therapeutical measures). Behavioral changes and insulin treatment adjustments may be made in a graduated manner (step-by-step), and a system- atic reinforcement is critical after the goals are achieved. Nutritional management is also an integral part of initial and following programs of education. The provision of a diabetes professional team (doctors, educators or diabetes nurse specialists, nutritionists or dieticians, and podiatrists or chiropodists) is also necessary as well as a continuing education for the professional staff. Several factors should be considered for a good therapy, including patient’s lifestyle, physical activity, dietary habits, glucose self-monitoring, correct time to injection (some patients may take regular insulin 5–15 min before the meal, instead of 30 min before), insulin dosage adjustments, usual injection sites and, finally, possible interactions with other drugs. How to avoid hypoglycemia, what to do during an episode of hypoglycemia or the correct behavior during acute illness or stress must be included in the education program. Each visit should be an opportunity to assess the current level of self-management, the behavioral change and goal achievement. Overall glycemic control is optimized when education and motivation are emphasized. In this approach, every diabetic patient should be considered unique.

Suggested Reading

Anderson JH, Brunelle R, Koivisto VA: Reduction of post-prandial hyperglycemia and frequency of

hypoglycemia in IDDM patients on insulin analog treatment. Diabetes 1997;46:265–270. Campbell PJ, May ME: A practical guide to intensive insulin therapy. Am J Med Sci 1995;310:24–30. Diabetes Control and Complications Trial Research Group: The effect of intensive treatment of diabetes

on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 1993;329:977–986.

Dimitriadis G, Gerich J: Importance of timing of preprandial subcutaneous insulin administration in the management of diabetes mellitus. Diabetes Care 1983;6:374–377. Galloway JA, deShazo RD: Insulin chemistry and pharmacology; insulin allergy, resistance, and lipodys- trophy; in Rifkin H, Porte D (eds): Diabetes mellitus. Theory and Practice, ed 4. Amsterdam, Elsevier, 1990, pp 497–512.

Sane T, Helve E, Yki-Jarvinen H: One year’s response to evening insulin therapy in non-insulin-dependent diabetes. J Intern Med 1992;231:253–260. Strowing S, Raskin P: Insulin treatment and patient management; in Rifkin H, Porte D (eds): Diabetes mellitus. Theory and Practice, ed 4. Amsterdam, Elsevier, 1990, pp 514–525.

F. Belfiore, Institute of Internal Medicine, University of Catania, Ospedale Garibaldi, I–95123 Catania (Italy) Tel. +39 095 330981, Fax +39 095 310899, E-Mail francesco.belfiore@iol.it

Belfiore F, Mogensen CE (eds): New Concepts in Diabetes and Its Treatment. Basel, Karger, 2000, pp 90–102

Chapter VI

Overview of Diabetes Management: ‘Combined’ Treatment and Therapeutic Additions

F. Belfiore, S. Iannello

Institute of Internal Medicine, University of Catania, Ospedale Garibaldi, Catania, Italy

Lessons from Recent Large Trials on Diabetes Treatment

The Diabetes Control and Complication Trial (DCCT), a large multicenter study conducted on more than 1,400 type 1 diabetics (aged 12–39 years) for

a period of 7–10 years, has established that close blood glucose control (even if complete normalization of glycemic level was not obtained) reduces the frequency of late diabetic complications. Patients were assigned randomly to either intensive insulin therapy (3 or more daily injections or insulin pump, glucose self-monitoring 4 or more times per day, and frequent contact with

a diabetes health-care team) or conventional therapy (1 or 2 injections of insulin mixtures per day, less frequent monitoring and medical contacts). The target goals of therapy were markedly different. Compared to the conventional care group, the intensive care group showed lower glycated hemoglobin (by 1.5–2.0%) and mean glucose level (by 60–80 mg/dl), yet most of the intensive care patients group failed to achieve normal glycemic levels. However, intensive care reduced the development of retinopathy by 76% (and its progression by 54%), the risk of microalbuminuria by 39%, frank proteinuria by 54%, and clinical neuropathy by 60%. Major cardiovascular events were also reduced, although statistical significance was not reached, in any case excluding that intensive insulin therapy may entail risk for macrovascular complications. The correlation of mean blood glucose with the frequency of retinopathy progression was linear, suggesting that there is no threshold glycemic level at which complications occur, so that any degree of improvement in glycemic control exerts beneficial effects on the progression of complications. These a diabetes health-care team) or conventional therapy (1 or 2 injections of insulin mixtures per day, less frequent monitoring and medical contacts). The target goals of therapy were markedly different. Compared to the conventional care group, the intensive care group showed lower glycated hemoglobin (by 1.5–2.0%) and mean glucose level (by 60–80 mg/dl), yet most of the intensive care patients group failed to achieve normal glycemic levels. However, intensive care reduced the development of retinopathy by 76% (and its progression by 54%), the risk of microalbuminuria by 39%, frank proteinuria by 54%, and clinical neuropathy by 60%. Major cardiovascular events were also reduced, although statistical significance was not reached, in any case excluding that intensive insulin therapy may entail risk for macrovascular complications. The correlation of mean blood glucose with the frequency of retinopathy progression was linear, suggesting that there is no threshold glycemic level at which complications occur, so that any degree of improvement in glycemic control exerts beneficial effects on the progression of complications. These

episodes, often not accompanied by the classical symptoms (intensive treatment reduces the adrenergic response to hypoglycemia), which makes intensive treatment less appropriate for some people (hypoglycemia unawareness, special occupations, children, old people, etc.). Finally, it should be noted that the DCCT results were obtained through a close cooperation between the patients themselves and an expert team, primarily nurse educators and dieticians. There- fore, it may not be easy to follow the DCCT criteria in everyday clinical practice.

The data from DCCT conclusively demonstrate that in type 1 diabetes the control of blood glucose really matters to prevent late complications. A recently concluded multicenter investigation on a very large study population (?5,000 patients), the United Kingdom Prospective Diabetes Study (UKPDS), whose results were presented at the European Association for the Study of Diabetes in Barcelona, September 1998, has obtained similar results in type

2 diabetic patients. As summarized by Laakso [1999], this study has shown that, compared to ‘diet alone’, the intensive control of blood glucose (regardless of the treatment used – sulfonylureas, metformin or insulin) reduced retinopathy or nephropathy by 25%, myocardial infarction by 16% and any diabetes-

related endpoint by 12%. For every one percentage point reduction in HbA 1c , there is a 35% reduction in retinopathy, nephropathy or neuropathy, and a 25% reduction in diabetes-related deaths (stroke frequency was not affected). As observed in the DCCT, there was no evidence of any glycemic threshold for micro- or macrovascular complications. With strict metabolic control, the risk of hypoglycemic episodes increased. Obese type 2 diabetic patients treated with metformin, compared with diet treatment, had even more pronounced benefits, showing reduction of 32 and 42% of diabetes-related endpoints and diabetes-related deaths, respectively, as well as a 36% reduction of all-cause mortality. In addition, they gained less weight and had fewer hypoglycemic episodes compared to the insulin- or sulfonylurea-treated patients.

The UKPDS also pointed out that type 2 diabetic patients with tight control of blood pressure (mean 144/82 mm Hg), obtained either by ACE inhibitors or b-blockers, compared to the untreated group (154/87 mm Hg), showed reduction of any diabetes-related endpoint (by 24%), diabetes-related deaths (by 32%), stroke (by 44%) and microvascular complications (by 37%). Reduction of myocardial infarction of 21% occurred but did not reach statistical significance.

It should be noted that in the UKPDS the treatment goal of maintaining fasting glycemia below 6 mmol/l (108 mg/dl) was not achieved. Strict metabolic control would consist of keeping glycemia below 10 mmol/l or 180 mg/dl at It should be noted that in the UKPDS the treatment goal of maintaining fasting glycemia below 6 mmol/l (108 mg/dl) was not achieved. Strict metabolic control would consist of keeping glycemia below 10 mmol/l or 180 mg/dl at

2 diabetes for preventing micro- and macrovascular complications. UKPDS also has evidenced that about 50% of newly diagnosed type 2 diabetic patients already show early signs of complications. This study has also showed that treatment with insulin or sulfonylureas is not harmful. However, this study did not demonstrate that this is also the case for elderly diabetic patients. Moreover, metformin was compared with other intensive treatments combined, not separately, with insulin and sulfonylureas. Concerning the possible negative effects of the association sulfonylurea-metformin, UKPDS did not provide sufficient evidence to suggest that this combination should not be used. Not all possible therapeutical combinations were tested, as, for instance, the combination insulin-metformin, which might bear the advantage that weight gain is prevented. Finally, it should be noted that the glucose levels fixed as therapeutical goal in the UKPDS may not be achievable in all patients; individual patient targets should be defined in relation to age and other risk factors.

On the basis of the UKPDS data, the British Diabetic Association recom- mends that the treatment should be aimed at the following goals: blood pressure levels of 140/80 mm Hg or below; HbA 1c levels of 7.0% (or within 1% of the upper end of the laboratory’s normal range); fasting blood glucose levels of 4–7 mmol/l (72–126 mg/dl), and self-monitored blood glucose levels before meals of 4–7 mmol/l (72–126 mg/dl).

According to the IDF guidelines [1999] for type 2 diabetes, the risk for vascular complications as related to metabolic compensation (blood glucose and HbA 1c ) is as follows: ‘Low risk’: HbA 1c (DCCT standardized) p6.5%; fasting/preprandial ve- nous plasma glucose (VPG) =100 mg/dl (6.0 mmol/l); fasting/preprandial self- monitored blood glucose (SMBG) =100 mg/dl (p5.5 mmol/l); postprandial SMBG =135 mg/dl (=7.5 mmol/l).

‘Arterial risk’: HbA 1c > 6.6–7.5%; fasting/preprandial VPG>110–125 mg/dl (6.1–6.9 mmol/l); fasting/preprandial SMBG>100–109 mg/dl (5.6–6.0 mmol/l); postprandial SMBG>135–160 mg/dl (7.5–9.0 mmol/l).

‘Microvascular risk’: HbA 1c ? 7.5%; fasting/preprandial VPG?125 mg/dl (?7 mmol/l); fasting/preprandial SMBG q110 mg/dl (q6.0 mmol/l); postprandial SMBG ?160 mg/dl (?9.0 mmol/l).

Role of Education