Effects of early use of pioglitazone in combination with metformin in patients with newly diagnosed type 2 diabetes.

BACKGROUND: Type 2 diabetes is characterised by a progressive decline in HbA1c control over time. Early combination therapy, rather than sequential introduction of individual oral glucose-lowering agents, has been proposed to prevent this gradual rise in HbA1c. This observational study assessed the effect of early dual combination oral glucose-lowering therapies within 6 months of diagnosis in newly diagnosed, drug-naïve patients with type 2 diabetes. PATIENTS AND METHODS: This was an observational, open-label, non-randomised study in newly diagnosed patients with type 2 diabetes, aged 35-70 years, with HbA1c levels > 8.0% at diagnosis or > 7.0% at the 3-6-month follow-up. Patients were allocated to dietary management alone if the HbA1c level was 7.0-8.0% at diagnosis. Metformin combined with gliclazide, repaglinide, or pioglitazone was given at diagnosis if the HbA1c was > 8.0%. Similar treatments were introduced at 3-6 months if the HbA1c was > 7.0%. Over a 3-year period, HbA1c was measured at 3-monthly intervals. All patients underwent regular dietetic review. Target HbA1c was < or = 7.0%. RESULTS: 416 patients were considered eligible for inclusion, with a mean (+/- SD) age of 54.1 +/- 9.2 years, BMI of 33.5 +/- 6.1 kg/m2, and baseline HbA1c of 8.6 +/- 1.7%. A mixed model analysis of variance on the 178 patients who started with combination therapy, either immediately or after a 3-6 month period on diet, showed that metformin plus gliclazide, repaglinide, or pioglitazone was associated with a gradual increase in HbA1c values. Amongst those patients treated with the metformin/pioglitazone combination there was an estimated 0.1% increase in HbA1c/year. This was much less pronounced than the rises seen in HbA1c/year of 0.5% with the metformin/gliclazide and metformin/repaglinide combinations. CONCLUSIONS: This preliminary analysis of an observational, non-randomised, open-label ongoing study has shown that early use of combination therapy at time of diagnosis or within the first 3-6 months following diagnosis with metformin plus pioglitazone in newly diagnosed type 2 diabetes results in a slower deterioration in glycaemic control than that with metformin combined with either gliclazide or repaglinide. This may be due to the beta-cell protective properties of pioglitazone. These results need to be confirmed by further studies with a more robust design and methodology.

Selection of transducer material for use with 'optical' foot pressure systems.

'Optical' foot pressure systems, or pedabarographs, use a white plastic or rubber material as the transducer. In the past, materials have been used which are not appropriate for calibrated measurements, particularly in dynamic studies (i.e. walking measurements). We describe a simple method for selecting transducer materials and make comparisons between commonly used materials.

Foot pressure studies in the assessment of forefoot arthroplasty in the rheumatoid foot.

To assess the results of forefoot arthroplasty, dynamic and static foot pressure studies have been made of the rheumatoid foot in both a prospective study group of 60 feet and in a retrospective study group of 18 feet. Significant reductions of pressure in the forefoot were found. Problems associated with the first and fifth metatarsals were considered.

Sinus tachycardia in term infants preceding sudden infant death.

The quantities of sinus tachycardia in 24-h recordings of the electrocardiogram from 16 full-term infants (greater than or equal to 37 weeks gestation) who were subsequently victims of the sudden infant death syndrome (SIDS), from 230 randomly selected age-matched full-term survivors and from 64 full-term survivors matched for age and birth weight were measured by computer and manual analysis techniques. Of 16 infants dying of SIDS, 7 had elevated levels of sinus tachycardia (greater than 95th centile in controls) (P less than 0.01). Although high levels of sinus tachycardia might be of value in identifying infants at high risk of SIDS, these encouraging findings must first be validated by further prospective studies.

The natural history of foot pressure abnormalities in neuropathic diabetic subjects.

The pressures under the feet of 39 subjects with diabetic neuropathy were initially assessed during walking using an optical pedobarograph. The upper limit of normality for pressure readings in non-diabetic subjects had previously been established as 10 kg/sq.cm. These subjects were then followed for a mean period of 3 years after which foot pressure studies were repeated. 39 feet had abnormal results when initially studied, compared with 33 at the follow-up study (p = NS). However, changes in the distribution of pressure under the metatarsal heads were seen in 13 feet, while 20 feet showed changes in abnormal pressures under the same site. Recurrent metatarsal ulcers occurred in 6 feet during the study, with 5 occurring at documented sites of high pressure. It is concluded that important changes in the distribution and level of pressures under diabetic neuropathic feet occur during a relatively short time. As it has previously been demonstrated that increased foot pressures are associated with foot ulceration, it is important for the orthotist to re-assess the feet regularly to establish whether significant changes in pressure distribution that might warrant new insoles or footwear have occurred.

Abnormalities of foot pressure in early diabetic neuropathy.

Dynamic foot pressure has been studied in 44 diabetic subjects of mean age 52 years with no clinical evidence of neuropathy and in an age and sex matched non-diabetic control group. Vibration perception threshold (VPT), sensory (SCV), and motor conduction velocities (MCV) were also measured in the diabetic subjects. Sixteen diabetic subjects (Group A) had abnormally high pressures under the metatarsal heads (greater than 10 kg/cm2), whereas the remaining 28 diabetic subjects had normal results (Group B). The ratio of toe to metatarsal head loading (normal 0.112) was significantly reduced in Group A (0.077) compared to Group B (0.127: p less than 0.05). VPT and sural nerve SCV were also significantly abnormal in Group A subjects compared with Group B (p less than 0.005 and p less than 0.02, respectively), though there were no differences in MCV. A significant inverse correlation was obtained between toe loading and VPT. It is concluded that abnormalities of foot pressure occur in early sensory neuropathy and may precede clinical abnormalities. Assessment of the toe-loading ratio may provide a sensitive measure of motor dysfunction in early diabetic neuropathy.

Analysis of the heart rate and breathing patterns of infants destined to suffer sudden infant death syndrome: probability density function analysis.

From a prospective study into the sudden infant death syndrome in which 24-h recordings of the ECG and respiratory waveform (abdominal wall movement) were made on a population of full-term infants, 22 recordings were obtained on 16 infants who subsequently suffered sudden infant death syndrome. The probability density function for the instantaneous heart rate and the breath to breath intervals and their randomly variabilities were calculated for these 22 recordings and for a control group of 324 infants randomly selected from the remainder of the population. A principal components analysis was then performed to classify the data and to make comparisons between infants. The infants in the analysis were divided into three postnatal age groups. No differences were found between the sudden infant death syndrome cases and the control group for the breath to breath intervals and its variability or for the instantaneous heart rate. Three sudden infant death syndrome cases lay outside the range of values for the heart rate variability at 6 wk of age.

Cardiovascular effects of spinal subarachnoid anaesthesia. A study in patients with chronic spinal cord injuries.

Spinal anaesthesia using 1.2 ml of hyperbaric cinchocaine was found to abolish the autonomic hyper-reflexic cardiovascular responses to bladder distension and produced little alteration in cardiovascular measurements.

Respiratory and heart rate patterns in infants destined to be victims of sudden infant death syndrome: average rates and their variability measured over 24 hours.

From a prospective study in which 24 hour recordings of the electrocardiogram and respiratory activity (abdominal wall movement) were made on a population of full term infants, 22 recordings were obtained from 16 infants who later were victims of the sudden infant death syndrome. The average heart rate, average heart rate variability, average breath to breath interval, and average breath to breath interval variability over the whole of each recording for the 22 recordings were compared with those from a control group of 324 infants selected at random from the rest of the population. No significance was found in the number of recordings from those infants who suffered the sudden infant death syndrome which lay outside the 5th-95th percentile range of the control group for the four variables studied. In a group comparison no difference was found between the sudden infant death syndrome group and the controls either in terms of the respiratory variables studied or in terms of the average heart rate variability. The results did, however, suggest that there may be a group difference in terms of the average instantaneous heart rate.

Plantar pressure measurements and the prevention of ulceration in the diabetic foot.

Static and dynamic measurements of foot pressure have been carried out on three groups of subjects: diabetic patients with neuropathy (with and without a history of ulceration), diabetic patients with no neuropathy, and normal subjects as controls. In many cases both techniques of measurement detected areas of abnormally high pressure under the foot, but in some cases a particularly high-pressure spot was detected on only one of the tests and sometimes both methods were needed to reveal all the areas of the foot which might be considered to be at risk. The dynamic measurements tended to show multiple areas of high pressure better than the static measurements. Our results indicate the importance of making both types of measurement when seeking to devise suitable means of protecting the foot from ulceration.

Reduction of abnormal foot pressures in diabetic neuropathy using a new polymer insole material.

The precise pressures and loads under 69 neuropathic feet have been measured during walking using a modified microprocessor-controlled optical system. Abnormally high pressures were demonstrated in 94% of feet with a history of foot ulceration, with pressures as high as 20-30 kg X cm-2 under the forefoot. All subjects were also studied using a new visco-elastic polymer material recently used for insole manufacture. A reduction in pressure was demonstrated that was proportional to peak pressure (linear regression line correlation coefficient of 0.91; P less than 0.001). We conclude that this material causes a significant reduction in the abnormally high pressures recorded under neuropathic feet, and should provide a useful insole for the management of patients at risk of neuropathic foot ulceration.