Position Statements

Diabetes Hongkong 2005
Position Statements on Diabetes Management
Promoting early diagnosis and tight glucose control

Sponsored by GlaxoSmithKline Educational Grant

POSITION STATEMENT 1

- DEFINITION, CLASSIFICATION AND DIAGNOSIS OF DIABETES AND OTHER DYSGLYCAEMIC CATEGORIES

Diabetes mellitus is characterized by hyperglycaemia resulting from defects in insulin secretion, insulin action, or both. Deficient action of insulin on target tissues leads to abnormalities in carbohydrate, fat and protein metabolism. The classification of diabetes is determined by the aetiological process rather than by the treatment modality. The vast majority of cases of diabetes fall into two broad categories, namely, type 1 and type 2 diabetes mellitus.

Type 1 diabetes
In type 1 diabetes, the cause is an absolute deficiency of insulin secretion. Insulin therapy is required for survival and subjects with type 1 diabetes are prone to ketoacidosis. This form of diabetes results from a cellular-mediated autoimmune destruction of β-cells of the pancreas. Immunological evidence for β-cell autoimmunity is usually evident and autoantibodies directed to the islet cells and their components can be detected (islet cell autoantibodies, autoantibodies to insulin, glutamic acid decarboxylase and tyrosine phosphatase). There is a strong HLA association with linkage to the DQA and DQB genes. Presentation tends to be acute with marked symptoms of hyperglycaemia. Some forms of type 1 diabetes have no evidence of autoimmunity (idiopathic) and no known aetiologies can be identified.

Type 2 diabetes
Type 2 diabetes mellitus is more prevalent than type 1 diabetes and accounts for over 90% to 95% of those with diabetes in Asia. The metabolic defect in type 2 diabetes may range from predominantly insulin resistance with relative rather than absolute insulin deficiency to a predominantly secretory defect with insulin resistance. There are probably many different causes of this form of diabetes but the specific aetiologies are still not known. There is a strong genetic predisposition, more so than the autoimmune form of type 1 diabetes. However, the genetics of this form of diabetes are complex and remain poorly understood. Unlike type 1 diabetes, type 2 diabetes frequently goes undiagnosed for many years because the hyperglycaemia tends to develop gradually and is often not severe enough initially for the individual to notice any of the classic symptoms of hyperglycaemia. However, such patients are at risk of developing the micro- and macrovascular complications. The risk of developing this form of diabetes increases with age, obesity and lack of physical activity.

Specific type of diabetes
Diabetes can be caused by monogenetic defects in insulin secretory function in β-cells (eg. maturity-onset diabetes of the young, mutations in mitochondrial DNA) or in insulin action (eg. type A insulin resistance, leprechaunism). These specific monogenetic forms of diabetes are uncommon causes of diabetes.

Diabetes may develop secondary to any disease process that affects the pancreas (eg. pancreatitis, haemochromatosis). Other causes of diabetes include endocrinopathies (eg. acromegaly, Cushing’s syndrome), drugs or chemicals, and infections. Diabetes is also known to be associated with certain genetic syndromes like Down’s syndrome and Klinefelter’s syndrome.

Gestational diabetes
Gestational diabetes is defined as any degree of glucose intolerance with onset or first recognition during pregnancy. The definition applies regardless of whether insulin or only diet modification is used for treatment or whether the condition persists after pregnancy. Women with GDM should be screened for diabetes 6 weeks postpartum and should be followed up with subsequent screening for the development of diabetes or pre-diabetes.

Pre-diabetes
Pre-diabetes refers to subjects with impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT). These are an intermediate group of subjects whose glucose levels, although not meeting the criteria for diabetes, are nevertheless too high to be considered normal. Diagnosis of IFG is based on fasting glucose alone whereas diagnosis of IGT requires a 2-h oral glucose tolerance test (OGTT, 75g glucose load). The two tests do not necessarily detect the same individuals. There is a large body of evidence showing that individuals with IGT not only have an increased risk of progression to frank diabetes, but they also have an increased cardiovascular risk. The natural history and progression of IFG is not yet well characterized.

Diagnostic criteria of diabetes
Both the American Diabetes Association and the World Heath Organization have modified the diagnostic cut-off levels for diabetes mellitus in the late 1990s (1-3) and the revised criteria are shown in Table 1. The diagnosis of diabetes should always be confirmed by repeating the blood glucose measurement on another day, unless there is unequivocal hyperglycaemia with acute metabolic decompensation or other obvious symptoms. The 2-h glucose post oral glucose load is a more sensitive assay in detecting diabetes in most populations but the fasting plasma glucose is more reproducible and less costly. Fasting glucose measurement can be used as a screening test in individuals without risk factors for glucose intolerance. In those subjects with risk factors of glucose intolerance, such as a family history of diabetes, history of gestational diabetes, obesity, hypertension, an OGTT should be performed to minimize the chance of missing the diagnosis of diabetes or IGT.

REFERENCES

1. Expert Committee on the Diagnosis and Classification of Diabetes Mellitus: Report of the Expert Committee on the Diagnosis and Classification of Diabetes. Diabetes Care 1997;20:1183-1197
   
   
2. World Health Organization: Definition, Diagnosis and Classification of Diabetes Mellitus and its Complications: Part 1: Report of a WHO Consultation: Diagnosis and Classification of Diabetes Mellitus. Geneva, World Health Org., 1999.
   
   
3. Expert Committee on the Diagnosis and Classification of Diabetes Mellitus: Follow-up Report on the Diagnosis of Diabetes Mellitus. Diabetes Care 2003;26:3160-3167.
   

Table 1: Diagnostic criteria of diabetes and pre-diabetes

POSITION STATEMENT 2

- TARGETS FOR GLYCAEMIC CONTROL

Introduction

Diabetes mellitus and its complications is a major health problem in modern societies like Hong Kong . The estimated prevalence of type -2 diabetes mellitus is about 12.8% among adult population [ IDF Atlas 2005 ]. Not only DCCT, UKPDS and Kumamoto study proved the role of hyperglycaemia in development of diabetic complications especially the microvascular complications such as retinopathy, nephropathy and neuropathy, the data from these studies also provide strong evidence base for tight glucose control. 1-3 While life style modification such as weight control, health diet and exercise form the corner stone of our management of diabetic management, the availability of newer pharmaceutical agents extends our horizon and improve our treatment options. The achievement of the ideal or normal PG should be the goal whenever possible, but not at the risk of excessive hypoglycaemia . I t must be emphasized that the targets mentioned in this position paper are general guidelines that need to be tailored for each and every patient. 4-7 Therefore, physician and patient must together decide on feasible glycaemic goals to strive for that can be safely achieved.

I. Fasting plasma glucose :

Recommendations:

• Targets for glycaemic control must be determined on a patient by patient basis.
  
  
• Age, presence of complications and/or co-morbidities, prognosis, renal function, and risk of hypoglycaemia must all be taken into account when determining targets for glycaemic control.
  
  
• Modest glucose targets may need to be set for patients who have experienced severe or frequent hypoglycaemia.
  

II. Glycosylated haemoglobin (A1C)

As noted in Monitoring Glycaemic Control guidelines, A1C is both a predictor of the risk of complications and an indicator of how well blood glucose has been controlled over time and it is the accepted gold standard for monitoring glycaemic control. 8-11

Recommendations:

• When possible, patients must be encouraged to maintain an A1C level of 6.5% (or less if it can be easily achieved).
  
  
• The benefits of aggressively lowering A1C below 6.5% must be weighed against the risk of developing hypoglycaemia.
  
  
• Patients who cannot reach lower target levels should be informed that any decline in A1C will reduce the risk of complications.
  
  
• All measurements of A1C should be standardized according to DCCT-reference (the A1C normal range of DCCT is 4-6 %).

III. Post prandial plasma glucose

Data have demonstrated that post prandial glucose contributes significantly to the development of diabetic complications and overall blood glucose control i.e. A1c. 12-13

Post-prandial blood glucose levels also appear to be a better predictor of coronary heart disease . 14-15

The importance of patients regularly monitoring their blood glucose levels in the interval between A1C tests has been highlighted in the Monitoring Glycaemic Control guidelines.

Recommendations:

• Patients should aim for fasting/pre-prandial blood glucose less than 6 mmol/L.
  
  
• Patients should aim for post-prandial (peak) blood glucose less than 8 mmol/L (1-2 hours after meals).

IV. Special situations

Recommendations:

• During pregnancy, women should aim to keep their 2-hour post-prandial blood glucose level at less than 7.0 mmol/L. 16, 17

TABLE I: TARGETSOF GLYCAEMIC CONTROL :

REFERENCES

• Stratton IM, Adler AI, Neil HA, Matthews DR , Manley SE, Cull CA , et al. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ 2000; 321: 405-12.
  
  
• The 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.
  
  
• Ohkubo Y, Kishikawa H, Araki E, et al. Intensive insulin therapy prevents the progression of diabetic microvascular complications in Japanese patients with non-insulin-dependent diabetes mellitus: a randomized prospective 6-year study. Diabetes Res Clin Pract 1995;28:103-117.
  
• European Diabetes Policy Group 1999. A desktop guide to Type 2 diabetes mellitus. Diabet Med 1999; 16: 716-30.
  
  
• ADA Position Statement. Standards of medical care. Diabetes Care 2005; 28 (suppl 1): S4-S36.
  
  
• Canadian Diabetes Association Clinical Practice Guidelines Expert Committee. Canadian Diabetes Association 2003 Clinical Practice Guidelines for the Prevention and Management of Diabetes in Canada . Canadian Journal of Diabetes 2003; 27(Suppl 2): S18-S20.
  
  
• IDF Task Force on Clinical Practical Guidelines. Global Guideline for Type 2 Diabetes. International Diabetes Federation, 2005.
  
  
• Selvin E, Marinopoulos S, Berkenblit G, Rami T, Brancati FL, Powe NR, et al. Meta-analysis: glycosylated hemoglobin and cardiovascular disease in diabetes mellitus. Ann Intern Med 2004; 141: 421-31.
  
  
• Khaw KT, Wareham N, Bingham S, Luben R, Welch A, Day N. Association of hemoglobin A 1c with cardiovascular disease and mortality in adults: the European Prospective Investigation into Cancer in Norfolk . Ann Intern Med 2004; 141: 413-20.
  
  
• Nathan DM, Singer DE, Hurxthal K, Goodson JD. The clinical informational value of glycosylated hemoglobin assay. N Engl J Med 1984; 310: 341-46
  
  
• Rohlfing CL, Wiedmeyer H-M, Little RR, England JD, Tennill A, Goldstein DE . Defining the relationship between plasma glucose and HbA 1c. Diabetes Care 2002; 25: 275-78.
  
  
• Ceriello A, The possible role of postprandial hyperglycaemia in the pathogenesis of diabetic complications, Diabetologia 2003;46;M9-M16
  
  
• Monnier L, Lapinski H, Colette C, Contributions of Fasting and Postprandial Plasma Glucose Increments to the Overall Diurnal Hyperglycaemia of Type 2 Diabetic Patients, Diabetes Care 2003;26:881-5
  
  
• Rodriguez BL, Sharp DS, Lau N, Yano Katsuhiko, Burchfiel CM, Curb JD, Abbott RD, Glucose Intolerance and 23 Year Risk of Coronary Heart Disease and Total Mortality, Diabetes Care 1999;2:1262-5
  
  
• Glucose tolerance and mortality: comparison of WHO and American Diabetes Association diagnostic criteria. The DECODE study group. European Diabetes Epidemiology Group. Diabetes Epidemiology: Collaboration analysis Of Diagnostic criteria in Europe , Lancet 1999;354:617-21
  
  
• Asian-Pacific Type 2 Diabetes Policy Group. Type Diabetes 2 Practical Targets and Treatments (Third edition). Health Communications Australia and In Vivo Communications; Sydney , Australia , 2002.
  
  
• Caroline AC, F.R.A.N.Z.C.O.G., Janet EH et al. Effect of Treatment of Gestational Diabetes Mellitus on Pregnancy Outcomes. N Engl J Med 2005; 353:2477-86.

POSITION STATEMENT 3

- MONITORING GLYCAEMIC CONTROL

I. Glycosylated haemoglobin (A1C) testing

Haemoglobin A1C, also known as HbA1c or A1C, is the gold standard laboratory-based indicator of diabetes control and a predictor of the risk of diabetic complications. 1,2,3,4 Unlike daily glucose monitoring, which is subject to fluctuations throughout the day (see next section), A1C reflects the body’s average glucose level over the previous two to three months, the average RBC life span.

A1C, formed by the non-enzymatic addition of glucose to the N-terminal valine of the b -chain of HbA1, is one of the most extensively studied glycosylated haemoglobins, employed in various clinical trials including the Diabetes Control and Complications Trial (DCCT) and the United Kingdom Prospective Diabetes Study (UKPDS). It is therefore the preferred standard as an index of mean blood glucose and as a treatment goal in patient care and newly initiated research. 5,6 The American Diabetes Association recommends an A1C level of 7% or less to minimize risk of complications such as blindness, kidney failure, and amputations (see Targets for Glycaemic Control guidelines). 1

Recommendations:

• Perform A1C test at least two times a year in patients who meet treatment goals and whose self-monitored blood glucose results are stable.
  
  
• Measure A1C every two to three months in patients whose therapy has changed or who are not meeting glycaemic goals.
  
  
• A1C should be measured using a certified method and results should be DCCT-aligned.

II. Self-monitoring of blood glucose (SMBG)

Active patient participation in the management of diabetes leads to improved blood sugar control, which is key to minimizing the risk of devastating complications like blindness, heart and kidney disease, stroke, and amputations. In addition to laboratory measurement of A1C every few months, most people with diabetes benefit from SMBG. 7,8,9 This has long been accepted for diabetic subjects who require insulin, but its value in non-insulin requiring type 2 diabetics was unclear until recently. A meta-analysis published in 2005 concludes that as part of a multi-component diabetes management programme, SMBG confers better glycaemic control (shown by a greater reduction in A1C). 10 Therefore, for patients with type 2 diabetes on oral agent therapy, SMBG should be encouraged to facilitate achieving target glucose goals. Results of SMBG are also helpful in preventing hypoglycaemia, enhancing lifestyle flexibilities including physical activity and dietary choices, and adjusting medications. 6,11,12

Recommendations:

• SMBG is an essential part of daily management for all diabetic subjects using insulin or oral anti-hyperglycaemic drugs.
  
  
• It should include both preprandial and two-hour postprandial testing.
  
  
• Health care professionals should teach patients how to perform SMBG, interpret results, and guide management, with regular evaluation of such ability thereafter.
  
  
• As the accuracy of SMBG is equipment and user-dependent, metre results should be compared with simultaneous laboratory glucose measurement. Patient’s monitoring technique should be evaluated annually and when parameters of glycaemic control do not match metre readings.

III. Frequency of blood glucose self-monitoring

The frequency and timing of SMBG should be largely determined by a patient’s particular needs and goals. 7,9 Additional considerations include available resources, either to the individual or the country concerned. Daily monitoring is, however, essential for patients using insulin to monitor for and prevent asymptomatic hypoglycaemia and hyperglycaemia. 1,2,3

Recommendations:

• People with type 1 diabetes, pregnant women with pre-existing diabetes mellitus or pregnant women with gestational diabetes should measure their blood glucose three or more times a day.
  
  
• People with type 2 diabetes on insulin typically need to perform SMBG more frequently than those not requiring insulin.
  
  
• In well-controlled and stable patients with type 2 diabetes on oral agent therapy, testing blood glucose one or two days per week is acceptable; consistently well-controlled patients can test less frequently.
  
  
• Daily glucose measurements are necessary during illness and for poorly controlled or unstable patients until targets of control are achieved.
  
  
• Blood glucose must also be tested more often when adjusting oral medications or insulin doses.

IV. Urine glucose self monitoring

Urine glucose testing is not routinely recommended for the following reasons:

• It only gives a rough estimate of prevailing blood glucose.
  
  
• There is no information about glucose values below the renal threshold
  (approximately 10 mmol/L), which for many patients is the target range for glucose control nowadays.
  
  
• It gives rise to misleading results in situations where renal threshold is elevated (e.g. elderly) or low (e.g. pregnancy)
  
  
• It does not provide warning of impending hypoglycaemia.

Recommendations:

• SMBG is preferred.
  
  
• Urine glucose monitoring may be considered as an alternative or a complement only in situations where a patient cannot afford blood glucose testing or cannot use it for other reasons. 13

V. Ketone monitoring

If the body cannot get energy from glucose (because of lack of insulin), it uses fat instead. When fat is broken down, ketones are made. These acids are harmful to the body and their presence in urine is a sign that a patient is developing diabetic ketoacidosis (DKA), which is a potentially life-threatening acute complication particularly in type 1 diabetes and sometimes in type 2 diabetes. This can however be prevented if patients are educated about how to monitor and detect hyperglycaemia and ketonuria. 1,2 Metres are now also available to perform blood ketone monitoring.

Recommendations:

• Patients with type 1 diabetes should perform ketone testing during acute illness or stress or when blood glucose levels are persistently elevated (eg. > 16.7 mmol/L), during pregnancy, or in the presence of symptoms of DKA such as nausea, vomiting or abdominal pain.
  
  
• People with type 2 diabetes – If the conditions noted above are present, ketone testing should be considered.

VI. Continuous glucose monitoring (CGM)

Devices are now commercially available that allow for continuous glucose monitoring—24-hours a day for up to 3 days. With these sensor systems, a small probe is inserted under the skin and measurements are made every 5 minutes while the person carries on with normal activities of daily living.

Continuous glucose monitoring can help identify fluctuations and trends that would otherwise go unnoticed with standard A1C tests and intermittent finger stick measurements, allowing clinicians to modify treatment measures more precisely and improving glycaemic control in selected patients. However, the role of CGMS in improving diabetes outcomes remains to be established. 2,14 In the absence of convincing scientific evidence showing an advantage over standard SMBG, it cannot yet be recommended for widespread use.

REFERENCES:

1. ADA Position Statement. Tests of glycaemia in diabetes. Diabetes Care 2004; 27(S1): S91-S93.
   
   
2. Sacks DB, Bruns DE, Goldstein DE, et al. Guidelines and recommendations for laboratory analysis in the diagnosis and management of diabetes mellitus. Diabetes Care 2002; 25: 750-86.
   
   
3. McIntosh A, Hutchinson A, Home PD, et al. Clinical guidelines and evidence review for Type 2 diabetes: management of blood glucose. Sheffield : ScHARR, University of Sheffield , 2001.
   
   
4. Canadian Diabetes Association Clinical Practice Guidelines Expert Committee. Canadian Diabetes Association 2003 Clinical Practice Guidelines for the Prevention and Management of Diabetes in Canada . Canadian Journal of Diabetes 2003; 27(Suppl 2): S18-S20.
   
   
5. Nathan DM, Singer DE, Hurxthal K, Goodson JD. The clinical informational value of glycosylated hemoglobin assay. New England Journal of Medicine 1984; 310: 341-46.
   
   
6. Rohlfing CL, Wiedmeyer H-M, Little RR, et al. Defining the relationship between plasma glucose and HbA 1c. Diabetes Care 2002; 25: 275-78.
   
   
7. Norris SL, Engelgau MM, Narayan KMV. Effectiveness of self management training in type 2 diabetes: a systematic review of randomized controlled trials. Diabetes Care 2001; 24: 561-87.
   
   
8. Franciosi M, Pellegrini F, De Berardis G, et al. The impact of blood glucose self-monitoring on metabolic control and quality of life in type 2 diabetic patients: an urgent need for better educational strategies. Diabetes Care 2001; 24: 1870-77.
   
   
9. Jones H, Edwards L, Vallis TM, et al. Changes in diabetes self-care behaviors make a difference in glycaemic control: the Diabetes Stages of Change (DiSC) study. Diabetes Care 2003; 26: 732-737.
   
   
10. Sarol JN Jr, Nicodemus NA Jr, Tan KM, Grava MB . Self-monitoring of blood glucose as part of a multi-component therapy among non-insulin requiring type 2 diabetes patients: a meta-analysis (1966-2004). Curr Med Res Opin 2005 Feb; 21(2): 173-84.
    
    
11. Karter AJ, Ackerson LM, Darbinian JA, et al. Self-monitoring of blood glucose levels and glycaemic control: the Northern California Kaiser Permanente Diabetes Registry. Am J Med 2001; 111: 1-9..
    
    
12. Faas A, Schellevis FG, van Eijk JTM. The efficacy of self-monitoring of blood glucose in NIDDM subjects. A criteria-based literature review. Diabetes Care 1997; 20: 1482-86.
    
    
13. IDF position statement. The role of urine glucose monitoring in diabetes – a valuable technology in appropriate settings. March 2005.
    
    
14. Monsod TP, Flanagan DE, Rife F, et al. Do sensor glucose levels accurately predict plasma glucose concentrations during hypoglycaemia and hyperinsulinemia? Diabetes Care 2002; 25: 889-93.