Definitions for the levels of evidence (I–IV) can be found at the end of the "Major Recommendations" field.
Guidelines
- In both Type 1 and Type 2 diabetics glycosylated haemoglobin (HbA1c) should be maintained at or < 7% for primary prevention of diabetic nephropathy, and for prevention of progression from microalbuminuria to overt nephropathy. (Level I evidence for Type 1 diabetes – moderate volume; Level I evidence for Type 2 diabetes – small volume)
- Optimal glycaemic control - preprandial blood glucose 4.4–6.7 mmol/L and HbA1c < 7% carries increased risk of hypoglycaemia. (There is no evidence that tight control in Type 2 diabetics with overt nephropathy will alter outcome)
Suggestions for Clinical Care
(Suggestions are based on Level III and IV sources)
- The Australian Diabetes Association is attempting to standardize HbA1c assays nationally. Some older assays are falsely elevated by carbamylated Hb in chronic kidney disease (CKD).
- The risk of hypoglycaemia can be minimised by frequent blood glucose monitoring with appropriate intervention (AACE).
- There is evidence that renal damage rarely occurs in patients with either Type 1 or Type 2 diabetes if HbA1c is < 7.5% and postprandial blood glucose is < 10.1 mmol/L. Data from the Joslin Clinic (Type 1) suggests that a low incidence rate of diabetic nephropathy occurs when HbA1c < 8.0%. Lower levels of HbA1c may be required for macrovascular protection.
- A major limitation of the available data is that they do not identify the optimum level of control for particular patients, as there are individual differences in the risks of hypoglycaemia, weight gain, and other adverse effects.
- It is unclear how different components of multifactorial interventions (e.g., educational interventions, glycaemic targets, lifestyle changes, and pharmacological agents) contribute to the reduction of complications.
- There are no clinical trial data available for the effects of glycaemic control in patients with advanced complications, the elderly (> 65 years of age), or children < 13 years.
- In the United Kingdom Prospective Diabetes Study (UKPDS) and the Diabetes Control and Complications Trial (DCCT), intensive control trebled the risks of hypoglycaemia and increased weight gain.
- Epidemiological analyses suggest that there is no lower limit of A1c at which further lowering does not reduce risk of complications. However, the absolute risks and benefits of lower targets are unknown.
- The risks and benefits of an A1c goal of < 6% are currently being tested in an ongoing study (ACCORD = Action to Control Cardiovascular Risk in Diabetes) in Type 2 diabetes.
- Elevated post challenge (2-h oral glucose tolerance test) glucose values have been associated with increased cardiovascular risk independent of fasting plasma glucose (FPG) in some epidemiological studies. Postprandial plasma glucose (PPG) levels > 7.8 mmol/L are unusual in non-diabetics, although large evening meals can be followed by plasma glucose values up to 10 mmol/L.
- The longer patients can maintain a target HbA1c level of 7.0%, which is achievable with current methods, the greater their protection from nephropathy.
Definitions:
Levels of Evidence
Level I: Evidence obtained from a systematic review of all relevant randomized controlled trials (RCTs)
Level II: Evidence obtained from at least one properly designed RCT
Level III: Evidence obtained from well-designed pseudo-randomized controlled trials (alternate allocation or some other method); comparative studies with concurrent controls and allocation not randomized, cohort studies, case-control studies, interrupted time series with a control group; comparative studies with historical control, two or more single arm studies, interrupted time series without a parallel control group
Level IV: Evidence obtained from case series, either post-test or pretest/post-test
