Achieving Good Glycemic Control

Aim Provide practical guidance on improving diabetes care through highlighting the need to: treat to glucose targets intensively monitor glycemia use a holistic approach to treatment involve experts in diabetes management

Type 2 diabetes: a global call to action Type 2 diabetes accounts for 85–95% of diabetes cases 333 million 350 300 250 Global prevalence of 200 diabetes (millions) 150 million 150 100 The number of people with diabetes, 85–95% of whom have type 2 diabetes, is expected to increase alarmingly in the coming decades. In 1985, an estimated 30 million people worldwide had diabetes, and in 2000, little over a decade later, the figure had risen to over 150 million. This figure is expected to rise to almost 333 million by the year 2025. The prevalence of diabetes is currently higher in developed countries than in developing countries, although increased urbanization, westernization and economic development in the developing world are contributing to a substantial rise in diabetes. This is likely to continue and will factor significantly in the forthcoming global epidemic of diabetes. Causes of the diabetes epidemic include population ageing, unhealthy diet, obesity and sedentary lifestyle. International Diabetes Federation. Facts & Figures. 2004. Available at: http://www.idf.org/home/ 30 million 50 1985 2000 2025 Year http://www.idf.org/home/

Obesity is a key driver of the diabetes epidemic 50–65% of the general population are obese or overweight1 The risk of developing type 2 diabetes increases with increasing weight2 It is estimated that half of all diabetes cases would be eliminated if weight gain could be prevented3 50–65% of the general population, not only in the US, Europe and Australia, but also in lower to moderate income countries such as Mexico, Egypt and the black population of South Africa, are obese (BMI  30.0 kg/m2) or overweight (BMI 25.0–29.9 kg/m2).1 The link between obesity and diabetes is well established,2 with the vast majority of individuals with type 2 diabetes being overweight or obese. While the risk of diabetes increases with weight, several studies have shown that moderate weight loss and increased physical activity can prevent or delay the development of type 2 diabetes.3–5 The Diabetes Prevention Program, for example, found that the participants who increased their physical activity and lost 5–7% of their body weight (10–15 pounds or 4.5–7 kg) reduced their progression to diabetes by 58% during the course of the study.3 1International Diabetes Federation. Press Release: 09 November 2004. Available at: http://www.idf.org/home/ 2Mokdad AH, et al. JAMA 2003; 289:76–79. 3Knowler WC, et al. N Engl J Med 2002; 346:393–403. 4Tuomilehto J, et al. N Engl J Med 2001; 344:1343–1350. 5Pan XR, et al. Diabetes Care 1997; 20:537–544. 1http://www.idf.org/home/; 2Mokdad AH, et al. JAMA 2003; 289:76–79. 3Knowler WC, et al. N Engl J Med 2002; 346:393–403.

Despite falling CHD mortality rates, diabetes increases the risk of CHD Factors  CHD deaths include  smoking, cholesterol, and BP and changes in treatments Factors  CHD deaths include diabetes and obesity 20,000 -20,000 Deaths prevented or postponed in 2000 -40,000 -60,000 In a recent model investigating the decline in coronary heart disease (CHD) deaths in England and Wales between 1981 and 2000, 58% of the decrease in CHD mortality was attributed to reductions in risk factors, such as smoking, blood pressure and cholesterol, while 42% was attributed to changes in medical treatments. This decrease in CHD mortality rates resulted in an estimated 68,230 fewer deaths in 2000. In contrast, however, obesity and diabetes had an opposite effect on CHD mortality, with each being associated with around 2,000–3,000 additional deaths. Unal B, et al. Circulation 2004; 109:1101–1107. -80,000 -100,000 Data from England and Wales between 1981 and 2000 in men and women aged 35–84 years There were 68,230 fewer CHD deaths than expected from baseline mortality rates in 1981 Unal B, et al. Circulation 2004; 109:1101–1107.

Individuals with diabetes are at increased risk of cardiovascular mortality Relative risk of death from any cause Relative risk of CHD death 20 15 Relative risk of death 10 5 Both diabetes and CHD are associated with a substantial increase in all-cause and CHD mortality. This was demonstrated in a prospective study of 91,285 US male physicians aged 40–84 years in which rates of all-cause and CHD mortality were compared between: men free of both diabetes and CHD (previous myocardial infarction and/or angina) at baseline (control group) men with a history of diabetes but not CHD men with a history of CHD but not diabetes men with a history of both diabetes and CHD. Individuals with both diabetes and CHD were at a particularly high risk of all-cause and CHD mortality. Lotufo P, et al. Arch Intern Med 2001; 161:242–247. Diabetes no CHD CHD no diabetes Diabetes and CHD Age-adjusted relative risk of death compared with men with no diabetes or CHD Lotufo P, et al. Arch Intern Med 2001; 161:242–247.

Mortality rate is doubled in individuals with diabetes Control Diabetes 35 Ratio 2.5 Ratio 2.2 Ratio 2.1 30 25 Mortality rate (deaths per 1,000 patient-years) 20 15 10 This analysis evaluated the 20-year mortality rate of men aged 44–55 years in the Whitehall, Paris Prospective and Helsinki Policemen studies. The mortality rate in men with diabetes was found to be twice as great as that in individuals without diabetes. 75% of the deaths in the Helsinki study were from cardiovascular disease, compared with 56% in Whitehall and 31% in France. Diabetes was associated with increases in both cardiovascular and non-cardiovascular mortality. Balkau B, et al. Lancet 1997; 350:1680. 5 Whitehall Study Paris Prospective Study Helsinki Policemen Study Balkau B, et al. Lancet 1997; 350:1680.

Type 2 diabetes is associated with serious complications Stroke Diabetic Retinopathy 2- to 4-fold increase in cardiovascular mortality and stroke5 Leading cause of blindness in adults1,2 Cardiovascular Disease 8/10 individuals with diabetes die from CV events6 Diabetic Nephropathy Serious microvascular and macrovascular complications of type 2 diabetes have a devastating effect on quality of life and impose a heavy burden on healthcare systems. Diabetic retinopathy: present in 21% of people at the time type 2 diabetes is diagnosed,1 diabetic retinopathy is the leading cause of new blindness among adults aged 20–74 years.2 Diabetic nephropathy: present in 18% of people diagnosed with diabetes;3 diabetes is a leading cause of end-stage renal disease.4 Stroke: diabetes is associated with a 2- to 4-fold increase in cardiovascular mortality and stroke.5 Cardiovascular disease: 75% of individuals with type 2 diabetes die from cardiovascular causes.6 Diabetic neuropathy: present in 12% of people at diagnosis,1 diabetic neuropathy affects approximately 70% of people with diabetes7 and is a leading cause of non-traumatic lower extremity amputations.8 In the UKPDS, 50% of individuals with diabetes already had complications at diagnosis.9 Early detection and treatment of diabetes is essential in order to reduce the impact of its serious complications. 1UK Prospective Diabetes Study Group. Diabetes Res 1990; 13:1–11. 2Fong DS, et al. Diabetes Care 2003; 26 (Suppl. 1):S99–S102. 3The Hypertension in Diabetes Study Group. J Hypertens 1993; 11:309–317. 4Molitch ME, et al. Diabetes Care 2003; 26 (Suppl. 1):S94–S98. 5Kannel WB, et al. Am Heart J 1990; 120:672–676. 6Gray RP & Yudkin JS. Cardiovascular disease in diabetes mellitus. In Textbook of Diabetes 2nd Edition, 1997. Blackwell Sciences. 7King’s Fund. Counting the cost. The real impact of non-insulin dependent diabetes. London: British Diabetic Association, 1996. 8Mayfield JA, et al. Diabetes Care 2003; 26 (Suppl. 1):S78–S79. 9UKPDS Group. Diabetologia 1991; 34:877–890. Diabetic Neuropathy Leading cause of end-stage renal disease3,4 Leading cause of non-traumatic lower extremity amputations7,8 1UK Prospective Diabetes Study Group. Diabetes Res 1990; 13:1–11. 2Fong DS, et al. Diabetes Care 2003; 26 (Suppl. 1):S99–S102. 3The Hypertension in Diabetes Study Group. J Hypertens 1993; 11:309–317. 4Molitch ME, et al. Diabetes Care 2003; 26 (Suppl. 1):S94–S98. 5Kannel WB, et al. Am Heart J 1990; 120:672–676. 6Gray RP & Yudkin JS. Cardiovascular disease in diabetes mellitus. In Textbook of Diabetes 2nd Edition, 1997. Blackwell Sciences. 7King’s Fund. Counting the cost. The real impact of non-insulin dependent diabetes. London: British Diabetic Association, 1996. 8Mayfield JA, et al. Diabetes Care 2003; 26 (Suppl. 1):S78–S79.

Individuals suffering ‘extreme problems’ in quality of life Diabetes 10.0 General population * 7.5 * Individuals reporting ‘extreme problems’ (%) * 5.0 2.5 * The burden of type 2 diabetes on quality of life was assessed in the T2ARDIS (Type 2 diabetes Accounting for a major Resource Demand In Society) survey by means of the EQ-5D.1 The EQ-5D is a questionnaire developed by the EuroQoL Group and designed as a generic measure of health-related quality of life (HRQoL).2 Comparison of the findings on the EQ-5D index was made with data from the 1996 Health Survey for England (HSE).3 T2ARDIS found that at least twice as many people with type 2 diabetes report ‘extreme problems’ in quality of life compared with the general population. In addition, people with type 2 diabetes report a significantly poorer quality of life (P < 0.01) than the general population in all age groups except for those aged more than 75 years.1 1Williams R, et al. The true costs of type 2 diabetes in the UK. Findings from T2ARDIS and CODE-2 UK. GlaxoSmithKline, 2002. 2Kind P. The EuroQoL instrument: an index of health-related quality of life. In Quality of Life and Pharmacoeconomics in Clinical Trials, 1996. Lippincott-Raven. 3Department of Health. Health Survey for England 1996. London: HMSO, 1997. * Mobility Self-care Usual activities Pain/ discomfort Anxiety/ depression *Significant versus general population Williams R, et al. The true costs of type 2 diabetes in the UK. Findings from T2ARDIS and CODE-2 UK, 2002. Department of Health. Health Survey for England 1996. London: HMSO, 1997.

Costs of diabetes are rising Indirect costs $132 140 Direct costs 120 $98 100 $92 80 Cost per year (US$ billion) 60 40 $20 The costs of diabetes are rising, as shown by estimates taken from four different analyses spanning 15 years.1–4 Costs are divided into direct costs (medical care) and indirect costs (lost productivity due to morbidity and mortality). Note that, although these data are taken from the US, the same trend is occurring globally. The full burden of diabetes is hard to measure because death records often fail to reflect the role of diabetes while the costs related to undiagnosed diabetes are unknown. 1Huse DM, et al. JAMA 1989; 262:2708–2713. 2Javitt JC & Chiang Y-P. In Diabetes in America, 1995; 601–611. NIH Publication No. 95–1468. 3American Diabetes Association. Diabetes Care 1998; 21:296–309. 4American Diabetes Association. Diabetes Care 2003; 26:917–932. 20 19871 19922 19973 20024 Year Estimated US costs 1Huse DM, et al. JAMA 1989; 262:2708–2713. 2Javitt JC & Chiang Y-P. In Diabetes in America, 1995; 601–611. NIH Publication No. 95–1468. 3American Diabetes Association. Diabetes Care 1998; 21:296–309. 4American Diabetes Association. Diabetes Care 2003; 26:917–932.

Hospitalizations account for the majority of the costs of managing type 2 diabetes Ambulatory care 18% Antidiabetic drugs 7% Other drugs 21% Hospitalizations 55% In the Cost of Diabetes in Europe – Type 2 (CODE-2) study, the total direct medical costs of type 2 diabetes in Belgium, France, Germany, Italy, the Netherlands, Spain, Sweden and the UK were estimated at €29 billion a year (1999 values) and the estimated annual costs per individual were €2,834. Hospitalizations accounted for the majority of overall costs (55%), with ambulatory care contributing 18%, antidiabetic drugs 7%, and all other drugs 21%. Jönsson B. Diabetologia 2002; 45 (Suppl.):S5–S12. = €29 billion/year Jönsson B. Diabetologia 2002; 45 (Suppl.):S5–S12.

Lowering HbA1c reduces the risk of complications Deaths related to diabetes 21% HbA1c Microvascular complications 37% 1% Data from the UKPDS demonstrated the substantial impact of good glycemic control on microvascular and macrovascular complications. In an analysis of these data, it was estimated that a 1% decrease in HbA1c, which reflects a measure of glycemia over the past 2–3 months, correlates with: 21% reduction in the risk of deaths related to diabetes (P < 0.0001) 37% reduction in the risk of microvascular complications (P < 0.0001) 14% reduction in the risk of myocardial infarction (P < 0.0001). These striking reductions in risk form the basis for diabetes management guidelines recommending aggressive targets for HbA1c in individuals with type 2 diabetes. Stratton IM, et al. BMJ 2000; 321:405–412. Myocardial infarction 14% Stratton IM, et al. BMJ 2000; 321:405–412.

Risk of complications decreases as HbA1c decreases 80 Microvascular complications Normal HbA1c levels 60 Incidence per 1,000 patient-years 40 Myocardial infarction 20 This analysis of data from the UKPDS determined the relation between HbA1c and the risk of microvascular or macrovascular complications. The incidence rates for both microvascular and macrovascular complications decreased with decreasing HbA1c. No lower threshold of glycemia existed (within the range analyzed) below which risk no longer decreased. That is, the lowest risk of complications is in those with HbA1c values in the normal range (< 6.0%). However, note that the benefits of intensive glycemic control strategies should always be weighed against the risk of hypoglycemia. Stratton IM, et al. BMJ 2000; 321:405–412. 5 6 7 8 9 10 11 Updated mean HbA1c (%) Stratton IM, et al. BMJ 2000; 321:405–412.

Diabetes management guidelines: HbA1c APPG (Asia Pacific)7 HbA1c < 6.5% CDA (Canada)4 HbA1c  7% NICE (UK)5 HbA1c 6.5–7.5% Australia8 HbA1c  7% ADA (US)1 HbA1c < 7% IDF (Europe)3 HbA1c  6.5% Guidelines from diabetes organizations recommend targets for HbA1c of 6.0–7.0% in individuals with type 2 diabetes: American Diabetes Association (ADA): < 7%1 American Association of Clinical Endocrinologists (AACE): 6.5%2 International Diabetes Federation (IDF) European Diabetes Policy Group:  6.5%3 Canadian Diabetes Association (CDA):  7%4 UK National Institute for Clinical Excellence (NICE): 6.5–7.5%5 Latin American Diabetes Association (ALAD): < 6–7%6 Asian-Pacific Type 2 Diabetes Policy Group (APPG): < 6.5%7 Australia:  7%.8 In addition, a target of HbA1c < 6% (normal range) is recommended in individuals in whom it can be achieved safely.1,4 However, less intensive glycemic goals may be indicated in some individuals, e.g. the elderly and those who are prone to hypoglycemia. 1American Diabetes Association. Diabetes Care 2004; 27 (Suppl. 1):S15–S34. 2American Association of Clinical Endocrinologists. Endocr Pract 2002; 8 (Suppl. 1):40–82. 3European Diabetes Policy Group. Diabet Med 1999; 16:716–730. 4Canadian Diabetes Association. Can J Diabetes 2003; 27 (Suppl. 2):S1–S152. 5National Institute for Clinical Excellence. 2002. Available at: http://www.nice.org.uk. 6ALAD. Rev Asoc Lat Diab 2000; Suppl. 1. 7Asian-Pacific Policy Group. Practical Targets and Treatments (3rd Edition). 8NSW Health Department. 1996. AACE (US)2 HbA1c  6.5% ALAD (Latin America)6 HbA1c < 6–7% 1American Diabetes Association. Diabetes Care 2004; 27 (Suppl. 1):S15–S34. 2American Association of Clinical Endocrinologists. Endocr Pract 2002; 8 (Suppl. 1):40–82. 3European Diabetes Policy Group. Diabet Med 1999; 16:716–730. 4Canadian Diabetes Association. Can J Diabetes 2003; 27 (Suppl. 2):S1–S152. 5National Institute for Clinical Excellence. 2002. Available at: http://www.nice.org.uk. 6ALAD. Rev Asoc Lat Diab 2000; Suppl. 1. 7Asian-Pacific Policy Group. Practical Targets and Treatments (3rd Edition). 8NSW Health Department. 1996.

Diabetes management guidelines: a sense of urgency “... the results of the UKPDS mandate that treatment of type 2 diabetes include aggressive efforts to lower blood glucose levels as close to normal as possible” “Diabetes must be… diagnosed earlier. And once diagnosed, all types of diabetes must then be managed much more aggressively” HbA1c American Diabetes Association1 The most recent diabetes management guidelines, e.g. from the American and Canadian Diabetes Associations,1,2 incorporate an increasing sense of urgency to treat diabetes both earlier and more aggressively in order to decrease the burden of diabetes-related complications. In addition, earlier diagnosis of diabetes is imperative in order to decrease the significant burden imposed by the condition. 1American Diabetes Association. Diabetes Care 2003; 26:S28–S32. 2Canadian Diabetes Association. Can J Diabetes 2003; 27 (Suppl. 2):1–163. Canadian Diabetes Association2 1American Diabetes Association. Diabetes Care 2003; 26:S28–S32. 2Canadian Diabetes Association. Can J Diabetes 2003; 27 (Suppl. 2):S1–S152.

Two thirds of individuals do not achieve target HbA1c Despite increasingly stringent diabetes management guidelines, current management of glycemia is sub-optimal, with only around a third of individuals with type 2 diabetes achieving their glycemic targets. In the US NHANES study, only 37% of individuals achieved the target HbA1c goal of < 7%1 In the European CODE-2 study, only 31% of individuals achieved the target HbA1c goal of < 6.5%.2 1Saydah SH, et al. JAMA 2004; 291:335–342. 2Liebl A, et al. Diabetologia 2002; 45:S23–S28. Saydah SH, et al. JAMA 2004; 291:335–342. Liebl A, et al. Diabetologia 2002; 45:S23–S28.

Proportion of individuals reaching target HbA1c is not improving over time NHANES (1988–1994) 60 NHANES (1999–2000) 48% 50 44% 37% 36% 40 34% 29% Individuals achieving goals (%) 30 20 7% 10 5% This review of data from the Third National Health and Nutrition Examination Study (NHANES III, 1988–1994) and NHANES 1999–2000 assessed trends in the proportion of patients achieving goals for HbA1c, blood pressure and total cholesterol over the past decade. A decrease was observed in the proportion of patients achieving HbA1c < 7.0% between 1988–1994 and 1999–2000. Over the same time period, the proportion of patients achieving blood pressure < 130/80 mmHg and total cholesterol < 200 mg/dL increased. Overall, the proportion of patients with good control (i.e. those achieving HbA1c < 7.0%, blood pressure < 130/80 mmHg and total cholesterol < 200 mg/dL) remained fairly constant (5% in 1988–1994 and 7% in 1999–2000). Action is needed to improve the proportion of individuals with type 2 diabetes achieving their treatment goals, in particular, for glycemic control. Saydah SH, et al. JAMA 2004; 291:335–342. HbA1c < 7.0% BP < 130/80 mmHg Total cholesterol < 200 mg/dL Good control* *Individuals achieving goals for HbA1c, blood pressure and total cholesterol Saydah SH, et al. JAMA 2004; 291:335–342.

Barriers to achieving good glycemic control Lack of clarity over definition of good glycemic control Inadequate monitoring of glycemia Complexity of managing hyperglycemia relative to dyslipidemia and hypertension A number of factors are likely to contribute to the complexities of controlling blood glucose levels in individuals with type 2 diabetes. The Global Partnership has identified several key areas that will help the diabetes care team to increase the proportion of individuals achieving good glycemic control and thus decrease the risk of complications. These include the need to: clarify the definition of good glycemic control ensure frequent monitoring of glycemia adopt a holistic approach to disease management increase involvement of specialist care units. Insufficient involvement of specialist care units

Lack of clarity over definition of good glycemic control

Although HbA1c targets are converging, good glycemic control is not reached ? Although the HbA1c targets recommended by international and national diabetes management guidelines are starting to converge, only a third of patients are achieving good glycemic control. To simplify and improve patient management and to resolve conflicting guidelines, the Global Partnership identified the need to clarify the definition of good glycemic control. Note the important role of clinical judgement to determine which patients can reasonably and safely achieve their glycemic targets. Consideration should be given to individual risk factors such as the patient’s age, prognosis, the presence of diabetes complications or co-morbidities and the patient’s risk for, and ability to recognize, symptoms of hypoglycemia.

What is good glycemic control? The Global Partnership recommends: Aim for good glycemic control = HbA1c < 6.5%* < 6.5% *Or fasting/preprandial plasma glucose < 110 mg/dL (6.0 mmol/L) where assessment of HbA1c is not possible Del Prato S, et al. Int J Clin Pract 2005; 59:1345–1355.

Inadequate monitoring of glycemia

Frequent monitoring of glycemia is important Cornerstone of diabetes care Ensures best possible glycemic control by: assessing efficacy of therapy guiding adjustments in diabetes care regimen, including diet, exercise and medications Effective diabetes management requires frequent monitoring of glycemia, particularly in individuals newly diagnosed with type 2 diabetes. This is essential in order to assess efficacy and to implement necessary modifications in treatment regimens. Regular assessment of glycemia leads to more proactive management of diabetes, which in turn can reap significant benefits in terms of patient outcomes. Frequent monitoring of glycemia also has benefits in terms of motivating the individual, particularly in relation to adherence to their regimens. Although patients may frequently monitor their glucose levels, they are often not aware of the significance of the results. Therefore, it is important that all members of the multidisciplinary team (including the patient) understand the significance of the results and take appropriate action.

Who should monitor glycemia? + Patient Self-monitoring of blood glucose Healthcare professionals Regular monitoring of HbA1c Diabetes care team Combined synergistic efforts of team are crucial to ensure effective monitoring of glycemic control Self-monitoring of blood glucose (SMBG) by the individual constitutes a crucial component of diabetes management. It is imperative for healthcare providers to evaluate each individual’s monitoring technique – both initially and at regular intervals thereafter – in order to ensure the accuracy of results. Benefits of self-management include improved HbA1c, avoidance of hypoglycemia and increased lifestyle flexibility. Members of the diabetes care team should supplement SMBG by providing regular monitoring of glycemia (preferably HbA1c). Together, the multidisciplinary diabetes care team has an essential role in ensuring regular and appropriate monitoring of glycemia. Through the provision of education, the multidisciplinary team approach can ensure that the individual with diabetes is motivated and informed with respect to interpreting blood glucose results and initiate appropriate changes.

Self-monitoring of blood glucose (SMBG) Regular SMBG increases the proportion of individuals achieving their glycemic targets Individuals should monitor postprandial glucose as part of their SMBG schedule Regular discussion of results with diabetes care team is essential HbA1c  8.0 HbA1c > 8.0 90% 80% Irregular SMBG Performers (42%) Not Monitored (37%) 70% Regular SMBG Performers (21%) 60% 50% 40% 30% 20% 10% There is evidence that regular self-monitoring of blood glucose (SMBG) increases the proportion of individuals with type 2 diabetes who achieve their glycemic targets. For example, in an assessment of data from > 3,000 clinic visits, the proportion of individuals achieving HbA1c  8% increased in those who regularly self-monitored blood glucose (70%) compared with those who reported irregular or no self-monitoring (18% and 22%, respectively).1 Given the well-established link between elevated postprandial glucose (PPG) levels and cardiovascular risk,2–4 it is also important that patients monitor PPG as part of their SMBG schedule. Results should be discussed regularly with the other members of the diabetes care team so that the treatment regimen can be adjusted accordingly where necessary. 1Blonde L, et al. Diabetes Care 2002; 25:245–246. 2Monnier L. E J Clin Invest 2000; 30 (Suppl. 2):3–11. 3Bonora E & Muggeo M. Diabetologia 2001; 44:2107–2114. 4Hanefeld M, et al. Diabet Med 2000; 17:835–840. 0% Blonde L, et al. Diabetes Care 2002; 25:245–246.

HbA1c monitoring HbA1c measures glycemia over preceding 2–3 months Regular assessment of HbA1c can lead to more proactive management of diabetes Two consecutive measurements of HbA1c  7.0% should lead to a review of the treatment algorithm Regular monitoring of HbA1c, which reflects a measure of glycemia over the previous 2–3 months, should be undertaken to ensure that patients are meeting and maintaining glycemic goals. Regular assessment of glycemia should lead to more proactive management of diabetes. For example, two consecutive measurements of HbA1c ≥ 7.0% should lead to a review of treatment, which in turn can reap significant benefits in terms of patient outcomes.

How often should HbA1c be monitored? The Global Partnership recommends: Monitor HbA1c every 3 months in addition to regular glucose self-monitoring Del Prato S, et al. Int J Clin Pract 2005; 59:1345–1355.

Complexity of managing hyperglycemia relative to dyslipidemia and hypertension

Influence of multiple risk factors and diabetes on CVD mortality No diabetes 140 Diabetes 120 100 Age-adjusted CVD death rate per 10,000 person-years 80 60 40 20 Many studies have highlighted the benefits of addressing the co-morbidities that commonly accompany type 2 diabetes and contribute to the severe complications that are associated with this disease. In the Multiple Risk Factor Intervention Trial (MRFIT),1 the number of risk factors (serum cholesterol > 200 mg/dL, cigarette smoking and systolic blood pressure > 120 mmHg) independently predicted cardiovascular disease mortality. In addition, MRFIT showed that diabetes was more powerful as a single risk factor than hypertension, total cholesterol or smoking. 1Stamler J, et al. Diabetes Care 1993; 16:434–444. None One only Two only All three Number of risk factors* *Serum cholesterol > 200 mg/dL, smoking, systolic blood pressure > 120 mmHg Stamler J, et al. Diabetes Care 1993; 16:434–444.

What are the priorities in diabetes management? Cholesterol? ? ? Glucose? Blood pressure? Type 2 diabetes is a complex condition to manage, requiring considerable expert knowledge in order to decrease the risk of diabetes-related complications. Management strategies should acknowledge that individuals with diabetes should receive intensive and effective treatment for all metabolic disturbances, including hyperglycemia, hypertension and dyslipidemia. This is reflected in current diabetes management guidelines,1–3 which include intensive targets for glycemic control, blood pressure and lipids. 1American Diabetes Association. Diabetes Care 2005; 28 (Suppl. 1):S4–S36. 2European Diabetes Policy Group. Diabet Med 1999; 16:716–730. 3Canadian Diabetes Association. Can J Diabetes 2003; 27 (Suppl. 2):S1–S152. ?

Individuals achieving Fewer individuals achieve goals for HbA1c versus lipids and blood pressure 80 72% 72% 70 58% 60 46% 50 Individuals achieving treatment goals (%) 40 30 15% 20 10 In order to decrease the risk of diabetes-related complications, individuals with diabetes should receive intensive and effective treatment for all metabolic disturbances, including hyperglycemia. However, data from several studies indicate that treatment of hyperglycemia may be more difficult to achieve relative to management of dyslipidemia and hypertension. For example, in the Steno-2 study, only 15% of individuals with diabetes assigned intensive treatment achieved their HbA1c goal of < 6.5%, compared with notably more individuals achieving goals for cholesterol (72%) or triglyceride (58%) levels or systolic/diastolic blood pressure (46% and 72%, respectively). This may be caused by a number of factors, for example: the complexity of managing hyperglycemia relative to dyslipidemia or hypertension differences in the efficacy of available antidiabetic medications relative to lipid-lowering agents or antihypertensive drugs greater public awareness and acceptance of the general health benefits of lowering lipids and blood pressure relative to glycemic control. Gaede P, et al. N Engl J Med 2003; 348:383–393. HbA1c < 6.5% Total cholesterol < 175 mg/dL Triglycerides < 150 mg/dL Systolic BP < 130 mmHg Diastolic BP < 80 mmHg Gaede P, et al. N Engl J Med 2003; 348:383–393.

FPG SBP TC = = HbA1c LDL ABPM Should glycemia be given more or less priority versus lipids and blood pressure? The Global Partnership recommends: Aggressively manage hyperglycemia, dyslipidemia and hypertension with the same intensity to obtain the best patient outcome FPG SBP TC DBP TGs = = Glycemic control Lipid-lowering Antihypertensive HbA1c HDL LDL ABPM Del Prato S, et al. Int J Clin Pract 2005; 59:1345–1355.

Insufficient involvement of specialist care units

Type 2 diabetes is a complex disorder Management of type 2 diabetes needs considerable expertise in order to: match medication to individual ‘phenotype’ manage complex drug regimens provide strong support for patient education Given the complexity of type 2 diabetes, relevant expertise is essential to identify the needs of the patient, including the characteristics of his or her profile or phenotype, e.g. age and duration of diabetes. The complementary skills of a multidisciplinary team is an optimal means of providing diabetes care. Ideally, it consists of the patient at the center, with additional members such as a physician, diabetes specialist nurse, dietician and podiatrist, in addition to other support services (depending on local healthcare resources). Extensive understanding of the pathophysiology of type 2 diabetes combined with a thorough knowledge of available antidiabetic medications is important for tailoring the treatment to the individual. In addition, most patients will be on complex drug regimens, requiring expert input in order to achieve the most appropriate balance of drugs, including antidiabetic, antihypertensive and lipid-lowering agents, aspirin and antiobesity drugs. Such complicated regimens require careful review, which should include vigilant monitoring and motivation, and robust support for the patient’s educational requirements. Involvement of all healthcare professionals with expertise in diabetes care, whether in primary or secondary care, could help more individuals achieve glycemic targets, and thus reduce the risk of diabetes-related complications. This is particularly important in those individuals considered to be at ‘high risk’.

Specialist input leads to better outcomes in type 2 diabetes In the Verona Diabetes Study, individuals attending a specialist diabetes center had a substantially improved chance of survival compared with those seen only by family physicians 17% Findings from the Verona Diabetes Study, which evaluated nearly 7,500 individuals with type 2 diabetes, suggest that specialist input will result in better outcomes. In a comparison of survival between individuals who exclusively consulted their family physician and those who also attended specialist diabetes centers, a 17% improvement in survival was observed in those receiving specialist care. Attending diabetes centers was found to be an independent predictor of survival even after adjusting for sex, age and diabetes therapy. Verlato G, et al. Diabetes Care 1996; 19:211–213. Verlato G, et al. Diabetes Care 1996; 19:211–213.

How can expertise be best utilized in diabetes management? The Global Partnership recommends: Refer all newly diagnosed patients to a unit specializing in diabetes care where possible Del Prato S, et al. Int J Clin Pract 2005; 59:1345–1355.