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Meta-Analysis
. 2012 Jun 13;2012(6):CD007543.
doi: 10.1002/14651858.CD007543.pub2.

Enhanced glucose control for preventing and treating diabetic neuropathy

Brian C Callaghan  1 , Ann A Little, Eva L Feldman, Richard A C Hughes
Affiliations
Meta-Analysis

Enhanced glucose control for preventing and treating diabetic neuropathy

Brian C Callaghan et al. Cochrane Database Syst Rev. .

Abstract

Background: There are two types of diabetes. Type 1 diabetes affects younger people and needs treatment with insulin injections. Type 2 diabetes affects older people and can usually be treated by diet and oral drugs. Diabetic neuropathy affects 10% of patients with diabetes mellitus at diagnosis and 40% to 50% after 10 years. Enhanced glucose control is the best studied intervention for the prevention of this disabling condition but there have been no systematic reviews of the evidence.

Objectives: To examine the evidence for enhanced glucose control in the prevention of distal symmetric polyneuropathy in people with type 1 and type 2 diabetes.

Search methods: We searched the Cochrane Neuromuscular Disease Group Specialized Register (30 January 2012), CENTRAL (2012, Issue 1), MEDLINE (1966 to January 2012) and EMBASE (1980 to January 2012) for randomized controlled trials of enhanced glucose control in diabetes mellitus.

Selection criteria: We included all randomized, controlled studies investigating enhanced glycemic control that reported neuropathy outcomes after at least one year of intervention. Our primary outcome measure was annual development of clinical neuropathy defined by a clinical scale. Secondary outcomes included motor nerve conduction velocity and quantitative vibration testing.

Data collection and analysis: Two authors independently reviewed all titles and abstracts identified by the database searches for inclusion. Two authors abstracted data from all included studies with a standardized form. A third author mediated conflicts. We analyzed the presence of clinical neuropathy with annualized risk differences (RDs), and conduction velocity and quantitative velocity measurements with mean differences per year.

Main results: This review identified 17 randomized studies that addressed whether enhanced glucose control prevents the development of neuropathy. Seven of these studies were conducted in people with type 1 diabetes, eight in type 2 diabetes, and two in both types. A meta-analysis of the two studies that reported the primary outcome (incidence of clinical neuropathy) with a total of 1228 participants with type 1 diabetes revealed a significantly reduced risk of developing clinical neuropathy in those with enhanced glucose control, an annualized RD of -1.84% (95% confidence interval (CI) -1.11 to -2.56). In a similar analysis of four studies that reported the primary outcome, involving 6669 participants with type 2 diabetes, the annualized RD of developing clinical neuropathy was -0.58% (95% CI 0.01 to -1.17). Most secondary outcomes were significantly in favor of intensive treatment in both populations. However, both types of diabetic participants also had a significant increase in severe adverse events including hypoglycemic events.

Authors' conclusions: According to high-quality evidence, enhanced glucose control significantly prevents the development of clinical neuropathy and reduces nerve conduction and vibration threshold abnormalities in type 1 diabetes mellitus. In type 2 diabetes mellitus, enhanced glucose control reduces the incidence of clinical neuropathy, although this was not formally statistically significant (P = 0.06). However, enhanced glucose control does significantly reduce nerve conduction and vibration threshold abnormalities. Importantly, enhanced glucose control significantly increases the risk of severe hypoglycemic episodes, which needs to be taken into account when evaluating its risk/benefit ratio.

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Conflict of interest statement

BC: none

AAL: none

RACH: after starting this review, RACH was invited to give expert testimony in a legal case in which an issue was whether treatment of diabetes would prevent or reduce neuropathy.

ELF: serves as the consulting neurologist to the National Institutes of Health on the Diabetes Control and Complications Trial (DCCT) and Epidemiology of Diabetes Interventions and Complications (EDIC) trials.

Figures

1
1
'Risk of bias' summary: review authors' judgments about each risk of bias item for each included study.
2
2
Forest plot of comparison: 1 Type 1 diabetes: enhanced versus standard therapy, outcome: 1.1 Annualized risk difference (%).
3
3
Forest plot of comparison: 1 Type 1 diabetes: enhanced versus standard therapy, outcome: 1.2 Incidence of clinical neuropathy after 5 years: risk ratio.
4
4
Forest plot of comparison: 1 Type 1 diabetes: enhanced versus standard therapy, outcome: 1.3 Annual change in peroneal nerve motor conduction velocity.
5
5
Forest plot of comparison: 1 Type 1 diabetes: enhanced versus standard therapy, outcome: 1.6 Annual change in vibration threshold in the feet.
6
6
Forest plot of comparison: 2 Type 2 diabetes: enhanced versus standard therapy, outcome: 2.1 Annualized risk difference (%).
1.1
1.1. Analysis
Comparison 1 Type 1 diabetes: enhanced versus standard therapy, Outcome 1 Annualized risk difference (%).
1.2
1.2. Analysis
Comparison 1 Type 1 diabetes: enhanced versus standard therapy, Outcome 2 Incidence of clinical neuropathy after 5 years: risk ratio.
1.3
1.3. Analysis
Comparison 1 Type 1 diabetes: enhanced versus standard therapy, Outcome 3 Annual change in peroneal nerve motor conduction velocity.
1.4
1.4. Analysis
Comparison 1 Type 1 diabetes: enhanced versus standard therapy, Outcome 4 Annual change in median nerve motor conduction velocity.
1.5
1.5. Analysis
Comparison 1 Type 1 diabetes: enhanced versus standard therapy, Outcome 5 Annual change in ulnar nerve motor conduction velocity.
1.6
1.6. Analysis
Comparison 1 Type 1 diabetes: enhanced versus standard therapy, Outcome 6 Annual change in vibration threshold in the feet.
2.1
2.1. Analysis
Comparison 2 Type 2 diabetes: enhanced versus standard therapy, Outcome 1 Annualized risk difference (%).
2.2
2.2. Analysis
Comparison 2 Type 2 diabetes: enhanced versus standard therapy, Outcome 2 Incidence of clinical neuropathy after different times: risk ratio.
2.3
2.3. Analysis
Comparison 2 Type 2 diabetes: enhanced versus standard therapy, Outcome 3 Annual change in median nerve motor conduction velocity.
2.4
2.4. Analysis
Comparison 2 Type 2 diabetes: enhanced versus standard therapy, Outcome 4 Annual change in vibration threshold in the feet.
2.5
2.5. Analysis
Comparison 2 Type 2 diabetes: enhanced versus standard therapy, Outcome 5 Death.
2.6
2.6. Analysis
Comparison 2 Type 2 diabetes: enhanced versus standard therapy, Outcome 6 Weight gain.
See this image and copyright information in PMC

Update of

References

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