Intervention Review

Enhanced glucose control for preventing and treating diabetic neuropathy

  1. Brian C Callaghan1,*,
  2. Ann A Little1,
  3. Eva L Feldman1,
  4. Richard AC Hughes2

Editorial Group: Cochrane Neuromuscular Disease Group

Published Online: 13 JUN 2012

Assessed as up-to-date: 30 JAN 2012

DOI: 10.1002/14651858.CD007543.pub2

How to Cite

Callaghan BC, Little AA, Feldman EL, Hughes RAC. Enhanced glucose control for preventing and treating diabetic neuropathy. Cochrane Database of Systematic Reviews 2012, Issue 6. Art. No.: CD007543. DOI: 10.1002/14651858.CD007543.pub2.

Author Information

  1. 1

    University of Michigan, Department of Neurology, Ann Arbor, Michigan, USA

  2. 2

    National Hospital for Neurology and Neurosurgery, MRC Centre for Neuromuscular Diseases, London, UK

*Brian C Callaghan, Department of Neurology, University of Michigan, 5017 BSRB, 109 Zina Pitcher Road, Ann Arbor, Michigan, MI 48109-2200, USA.

Publication History

  1. Publication Status: New
  2. Published Online: 13 JUN 2012




  1. Top of page
  2. Abstract
  3. Plain language summary
  4. アブストラクト
  5. 平易な要約


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.


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.


Plain language summary

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. アブストラクト
  5. 平易な要約

Enhanced glucose control for preventing and treating diabetic neuropathy

Diabetes is defined as high sugar levels in the blood. There are two forms of the disease. In type 1 diabetes, the body does not produce enough insulin. In type 2 diabetes, the body becomes less responsive to insulin. Regardless of the type of diabetes, many people develop a disabling neuropathy. Neuropathy is a condition that results in numbness, tingling, pain, or weakness that typically starts in the feet and progresses up the legs. The distribution is often described as a stocking glove pattern since the feet are affected first followed by the legs and fingers. The most common treatment for diabetes is control of blood sugar levels in an attempt to prevent the many complications, including neuropathy. This review identified 17 randomized studies that addressed whether more aggressive attempts to lower blood glucose levels prevent people from developing neuropathy. Seven of these studies were conducted in people with type 1 diabetes, eight in type 2 diabetes, and two in both types. However, only two studies in type 1 diabetes including 1228 participants and four studies in type 2 diabetes including 6669 participants investigated our primary outcome. In type 1 diabetes, there was a significant effect of more aggressive therapies in preventing neuropathy compared with standard treatment. In type 2 diabetes, more aggressive therapy was also beneficial in preventing symptoms and signs of clinical neuropathy, but the result was not statistically significant as measured by the primary method selected for this review. However, there was a significant positive effect on the amount of nerve damage measured with electrical nerve conduction tests and a special machine to measure the threshold of detection of vibration in both types of diabetes. Overall, the evidence indicates that more aggressive treatments of sugar levels delay the onset of neuropathy in both types of diabetes. No other treatments have proven effective to date. However, the beneficial effect has to be balanced against the significantly increased risk of dangerously low blood sugar levels that can occur in both types of diabetes and which can lead to brain injury amongst other issues.



  1. Top of page
  2. Abstract
  3. Plain language summary
  4. アブストラクト
  5. 平易な要約







糖尿病における強化血糖コントロールのランダム化比較試験について、Cochrane Neuromuscular Disease Group Specialized Register(2012年1月30日)、CENTRAL(2012年第1号)、MEDLINE(1966年~2012年1月)、EMBASE(1980年~2012年1月)を検索した。






本レビューでは、強化血糖コントロールが神経障害発現を予防するか検討した17件のランダム化研究を同定した。これらの研究のうち7件は1型糖尿病の人を、8件は2型糖尿病の人を、2件は両型を対象として実施されていた。1型糖尿病の計1,228名の参加者を対象に主要アウトカム(臨床的神経障害の発生率)を報告している2件の研究のメタアナリシスでは、強化血糖コントロール群において臨床的神経障害発現リスクの有意な低下を示し、年RDは-1.84%[95%信頼区間(CI)-1.11~-2.56]であった。2型糖尿病の参加者6,669名を対象に主要アウトカムを報告している4件の研究の同様の解析では、臨床的神経障害発現の年RDは-0.58%(95%CI 0.01~-1.17)であった。ほとんどの副次アウトカムは、どちらの集団においても強化治療を有意に支持する結果であった。しかし、どちらの型の糖尿病でも、低血糖事象を含む重度の有害事象が有意に増加した。


高品質のエビデンスによると、強化血糖コントロールは1型糖尿病において臨床的神経障害の発現を有意に予防し神経伝導および振動閾値異常を有意に減少させた。2型糖尿病において、強化血糖コントロールは臨床的神経障害の罹患率を低下させたが、正式には統計学的に有意ではなかった(P = 0.06)。しかし、強化血糖コントロールにより、神経伝導および振動閾値異常が有意に減少した。強化血糖コントロールにより重度の低血糖エピソードのリスクが有意に上昇したことは重要であり、リスク/利益比を評価する場合は考慮する必要がある。



  1. Top of page
  2. Abstract
  3. Plain language summary
  4. アブストラクト
  5. 平易な要約




監  訳: 相原 守夫,2012.10.31

実施組織: 厚生労働省委託事業によりMindsが実施した。

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