Understanding and treating painful diabetic neuropathy: time for a paradigm shift.

The pathogenesis of diabetic neuropathy (DN) continues to be unclear and as a result, progress in developing effective therapies has been disappointing. In particular, there is only limited understanding of why some patients suffer severe chronic pain, whilst others have painless symptoms. Assessment of the peripheral nerves frequently shows no differences between painful and painless DN. There is growing evidence that the nerve damage in DN is more generalized, including the central nervous system, and these central changes are key to the development and persistence of pain in DN. The advent of new radiological techniques provides us with non-invasive modalities to study central pathophysiological processes in greater detail. These insights are increasingly leading to the recognition that painful DN is a complex and heterogeneous disorder, which requires a multimodal approach to treatment.

Autonomic dysfunction and circadian blood pressure variations in people with impaired glucose tolerance.

AIMS: To assess circadian blood pressure variability in people with impaired glucose tolerance and a healthy control population. METHODS: Seventy-five people with impaired glucose tolerance and 40 healthy volunteers (frequency matched on 10-year age bands and sex) underwent a detailed neurological assessment. Autonomic neuropathy was detected by the five standard cardiovascular autonomic tests and heart rate variability was characterized by the triangle index. Diurnal indices were assessed by 24-h ambulatory blood pressure monitoring. Systolic and diastolic diurnal indices were defined as: (mean daytime blood pressure - mean night-time blood pressure) × 100/mean daytime blood pressure. RESULTS: Mean 24-h systolic and diastolic blood pressure was significantly higher in the group with impaired glucose tolerance compared with the control group [126 ± 12 (mean ± SD) vs. 117 ± 10, 75 ± 7 vs. 71 ± 6 mmHg, both P < 0.05). Systolic and diastolic diurnal indices and heart rate variability triangular index were significantly lower in people with impaired glucose tolerance compared with control subjects (9.1 ± 7.8 vs. 13.2 ± 5.4, 14.5 ± 9.7 vs. 18.4 ± 7.1 mmHg, 28.0 ± 8.4 vs. 39.5 ± 9.3, all P < 0.05). Differences in mean diastolic blood pressure, heart rate variability triangular index and the frequency of non-dippers between those with impaired glucose tolerance and control subjects seemed to be independent of BMI and the presence of cardiovascular autonomic neuropathy, as simultaneous adjustment for BMI and cardiovascular autonomic neuropathy had no major effect on the results. CONCLUSION: Our data suggest that people with impaired glucose tolerance have increased diastolic blood pressure and abnormal circadian blood pressure regulation, independent of obesity and the presence of cardiovascular autonomic neuropathy.

Acute hepatic injury following treatment of a long-acting insulin analogue overdose necessitating urgent insulin depot excision.

BACKGROUND: A 26-year-old man with Type 1 diabetes presented with an overdose of 4800 units of the long-acting insulin analogue, glargine (Lantus). Glucose supplementation of approximately 800 g/day was associated with acute hepatic injury. METHODS: On day 4, a depot of insulin was excised from the patient's abdominal wall; this was followed by a reduction in his glucose requirements and improvement in liver function. CONCLUSIONS: This report highlights the risk of acute hepatic injury during the treatment of insulin overdose and the importance of careful glucose supplementation. It also demonstrates how earlier excision of an insulin depot could potentially prevent this problem and hasten recovery.

HbA1c during pregnancy: its relationship to meal related glycaemia and neonatal birth weight in patients with diabetes.

OBJECTIVE: Although home blood glucose (HBG) profiles correlate closely with HbA1c, the strength of the relationship during pregnancy is unclear due to physiological changes which can induce subnormal HbA1c levels. We therefore aimed to establish the strength of the association between mean HBG profiles and HbA1c in diabetic pregnancies and whether HbA1c levels and glycaemic variability affects neonatal birth weight (NBW). STUDY DESIGN: 7-point glycaemic profiles performed throughout pregnancy were obtained retrospectively in 94 consecutive patients attending the diabetes antenatal clinic and compared to the corresponding mean HbA1c levels. RESULTS: There was a significant linear correlation between mean HBG and HbA1c (HbA1c=0.5HBG+3.1, r=0.71, p<0.0001). Multiple regression analysis demonstrated that both pre- and post-prandial HBG levels correlated significantly and independently with HbA1c, correlation coefficients (r) were 0.63 and 0.65, respectively both p<0.0001. Significant correlations were also observed in patients with gestational diabetes (n=67, mean HbA1c=6.11, r=0.67; p<0.0001) and type 1 diabetes (n=18, mean HbA1c=6.75, r=0.64; p=0.004). All meal related HBG measurements showed similar significant correlations with HbA1c (r values pre- and post-breakfast, pre- and post-lunch, pre- and post-tea and pre-bed are 0.56, 0.55, 0.59, 0.55, 0.56, 0.59, 0.51, respectively p<0.0001 for all time points). Post hoc analysis showed that NBW increased with higher levels of HbA1c; NBW (centiles)+/-S.D. for HbA1c <6.5% versus >6.5% was 78.9%+/-29.2 versus 90.2%+/-18.6, p=0.02. CONCLUSION: Mean HbA1c levels are closely correlated to all meal related glucose measurements during pregnancy. It is therefore a reliable indicator of overall glycaemic control among patients with diabetes during pregnancy.