Fuel metabolism during exercise in euglycaemia and hyperglycaemia in patients with type 1 diabetes mellitus--a prospective single-blinded randomised crossover trial.

AIMS/HYPOTHESIS: We assessed systemic and local muscle fuel metabolism during aerobic exercise in patients with type 1 diabetes at euglycaemia and hyperglycaemia with identical insulin levels. METHODS: This was a single-blinded randomised crossover study at a university diabetes unit in Switzerland. We studied seven physically active men with type 1 diabetes (mean +/- SEM age 33.5 +/- 2.4 years, diabetes duration 20.1 +/- 3.6 years, HbA1c 6.7 +/- 0.2% and peak oxygen uptake [VO2peak] 50.3 +/- 4.5 ml min(-1) kg(-1)). Men were studied twice while cycling for 120 min at 55 to 60% of VO2peak, with a blood glucose level randomly set either at 5 or 11 mmol/l and identical insulinaemia. The participants were blinded to the glycaemic level; allocation concealment was by opaque, sealed envelopes. Magnetic resonance spectroscopy was used to quantify intramyocellular glycogen and lipids before and after exercise. Indirect calorimetry and measurement of stable isotopes and counter-regulatory hormones complemented the assessment of local and systemic fuel metabolism. RESULTS: The contribution of lipid oxidation to overall energy metabolism was higher in euglycaemia than in hyperglycaemia (49.4 +/- 4.8 vs 30.6 +/- 4.2%; p < 0.05). Carbohydrate oxidation accounted for 48.2 +/- 4.7 and 66.6 +/- 4.2% of total energy expenditure in euglycaemia and hyperglycaemia, respectively (p < 0.05). The level of intramyocellular glycogen before exercise was higher in hyperglycaemia than in euglycaemia (3.4 +/- 0.3 vs 2.7 +/- 0.2 arbitrary units [AU]; p < 0.05). Absolute glycogen consumption tended to be higher in hyperglycaemia than in euglycaemia (1.3 +/- 0.3 vs 0.9 +/- 0.1 AU). Cortisol and growth hormone increased more strongly in euglycaemia than in hyperglycaemia (levels at the end of exercise 634 +/- 52 vs 501 +/- 32 nmol/l and 15.5 +/- 4.5 vs 7.4 +/- 2.0 ng/ml, respectively; p < 0.05). CONCLUSIONS/INTERPRETATION: Substrate oxidation in type 1 diabetic patients performing aerobic exercise in euglycaemia is similar to that in healthy individuals revealing a shift towards lipid oxidation during exercise. In hyperglycaemia fuel metabolism in these patients is dominated by carbohydrate oxidation. Intramyocellular glycogen was not spared in hyperglycaemia.

QTc interval and resting heart rate as long-term predictors of mortality in type 1 and type 2 diabetes mellitus: a 23-year follow-up.

AIMS/HYPOTHESIS: We evaluated the association of QT interval corrected for heart rate (QT(c)) and resting heart rate (rHR) with mortality (all-causes, cardiovascular, cardiac, and ischaemic heart disease) in subjects with type 1 and type 2 diabetes. METHODS: We followed 523 diabetic patients (221 with type 1 diabetes, 302 with type 2 diabetes) who were recruited between 1974 and 1977 in Switzerland for the WHO Multinational Study of Vascular Disease in Diabetes. Duration of follow-up was 22.6 +/- 0.6 years. Causes of death were obtained from death certificates, hospital records, post-mortem reports, and additional information given by treating physicians. RESULTS: In subjects with type 1 diabetes QT(c), but not rHR, was associated with an increased risk of: (1) all-cause mortality (hazard ratio [HR] 1.10 per 10 ms increase in QT(c), 95% CI 1.02-1.20, p = 0.011); (2) mortality due to cardiovascular (HR 1.15, 1.02-1.31, p = 0.024); and (3) mortality due to cardiac disease (HR 1.19, 1.03-1.36, p = 0.016). Findings for subjects with type 2 diabetes were different: rHR, but not QT(c) was associated with mortality due to: (1) all causes (HR 1.31 per 10 beats per min, 95% CI 1.15-1.50, p < 0.001); (2) cardiovascular disease (HR 1.43, 1.18-1.73, p < 0.001); (3) cardiac disease (HR 1.45, 1.19-1.76, p < 0.001); and (4) ischaemic heart disease (HR 1.52, 1.21-1.90, p < 0.001). Effect modification of QT(c) by type 1 and rHR by type 2 diabetes was statistically significant (p < 0.05 for all terms of interaction). CONCLUSIONS/INTERPRETATION: QT(c) is associated with long-term mortality in subjects with type 1 diabetes, whereas rHR is related to increased mortality risk in subjects with type 2 diabetes.

Apolipoprotein B as a long-term predictor of mortality in type 1 diabetes mellitus: a 15-year follow up.

OBJECTIVES: To evaluate the association of apolipoprotein B (apo B) with mortality due to all causes, to cardiac disease and to ischaemic heart disease (IHD) in subjects with type 1 diabetes mellitus. SUBJECTS: 165 subjects with type 1 diabetes included in the Swiss Cohort of the WHO Multinational Study of Vascular Disease in Diabetes were followed for 14.7+/-0.45 years. METHODS: Causes of death were obtained from death certificates, hospital records and postmortem reports. Using a parametric proportional hazards model the association of apo B with mortality rates was assessed by time-to-event analysis, including the absolute cumulative mortality risk over time for various apo B levels at baseline. RESULTS: Apo B was positively associated with all-cause mortality [hazard ratio (HR) 2.65 per g L-1 increase of apo B, 95% CI: 1.11-6.36, P=0.029], cardiac mortality (HR 11.64, 1.03-131.11, P=0.047) and IHD mortality (HR 9.36, 1.26-69.66, P=0.029). An apo B>or=0.96 g L-1 translated into a duplication of overall mortality hazard (HR 1.93, 1.00-3.72, P=0.050), and a sevenfold increase of mortality because of cardiac disease or IHD (HR 7.44, 1.44-38.42, P=0.017 and HR 7.38, 0.78-69.82, P=0.081). A baseline apo B of 1.5 g L-1 predicted an absolute cumulative risk to die over the next 10 years of 12.1% (5.2-31.7) for male and of 10.4% (4.7-26.1) for female subjects whereas risks were 6.3% (1.8-21.4) and 5.4% (0.8-15.8) for an apo B of 0.8 g L-1. CONCLUSION: Apo B is consistently associated with an increased mortality in type 1 diabetes.

Efficacy of drug eluting stents in patients with and without diabetes mellitus: indirect comparison of controlled trials.

OBJECTIVE: To examine whether polymer based coronary stents eluting sirolimus or paclitaxel are equally effective in patients with and without diabetes. METHODS: Systematic review and meta-analysis by indirect comparison of randomised controlled trials comparing stents eluting sirolimus or paclitaxel with conventional bare metal stents. The overall study population and patients with and without diabetes were analysed separately by using the ratio of incidence rate ratios (RIRR). RESULTS: The analysis was based on 10 trials (six with sirolimus, four with paclitaxel), 4513 patients (1146 patients with diabetes), 5755 years of follow up, and 2464 events. In patients without diabetes sirolimus eluting stents were superior to paclitaxel eluting stents with respect to in-stent (RIRR 0.21, 95% confidence interval (CI) 0.10 to 0.48, p < 0.001) and in-segment restenosis (RIRR 0.47, 95% CI 0.24 to 0.92, p = 0.027), target lesion revascularisation (RIRR 0.54, 95% CI 0.30 to 0.99, p = 0.045), and major adverse cardiac events (RIRR 0.46, 95% CI 0.26 to 0.83, p = 0.010). In patients with diabetes the two drug eluting stents did not differ significantly in any of these end points. Meta-regression analysis showed a significant difference between patients with and without diabetes (tests for interaction for in-stent and in-segment restenosis, p = 0.036 and p = 0.016). CONCLUSION: Indirect evidence indicates that sirolimus eluting stents are superior to paclitaxel eluting stents in patients without diabetes but not in patients with diabetes.