Short-term oxygen administration restores blunted baroreflex sensitivity in patients with type 1 diabetes.

AIMS/HYPOTHESIS: We hypothesised that the blunted baroreflex sensitivity (BRS) typical of type 1 diabetes is caused by a higher degree of tissue hypoxia in diabetes, and tested whether oxygen increased BRS and ventilation less, equally or more than in healthy control participants (the latter suggesting higher tissue hypoxia). In addition, we also considered the possible interference between oxygen and breathing pattern. METHODS: In 96 participants with type 1 diabetes and 40 age-matched healthy controls, we measured BRS (average of six different standard methods), oxygen saturation, end-tidal carbon dioxide and ventilation changes during spontaneous and controlled breathing at 15 and six breaths/min, in normoxia and during 5 l/min oxygen administration. RESULTS: BRS was blunted and blood pressure higher in diabetic participants during spontaneous breathing (p < 0.05). BRS increased with oxygen during spontaneous breathing in diabetic (p < 0.001) but not in control participants, and with oxygen the difference in BRS was no longer significant. Slow breathing in normoxia restored BRS to a similar extent to giving oxygen. Oxygen increased systolic and diastolic blood pressure, RR interval, heart rate variability, minute ventilation and tidal volume to a greater extent in diabetic patients than in controls, and decreased carbon dioxide similarly to controls. CONCLUSIONS/INTERPRETATION: The increased response to hyperoxia suggests a pre-existing condition of tissue hypoxia that functionally restrains parasympathetic activity in patients with type 1 diabetes. Autonomic abnormalities can be partially and temporarily reversed by functional manoeuvres such as slow breathing or oxygen administration through enhancement of parasympathetic activity and/or correction of tissue hypoxia.

Deep breathing improves blunted baroreflex sensitivity even after 30 years of type 1 diabetes.

AIMS/HYPOTHESES: Cardiovascular autonomic neuropathy is associated with increased morbidity in patients with type 1 diabetes. Although it is conventionally considered to be an organic, irreversible disorder, we previously demonstrated in patients with short-duration type 1 diabetes that reduced baroreflex sensitivity (BRS) could be corrected by slow, deep breathing, indicating a functional component to the disorder. We have now tested whether autonomic abnormalities in long-term diabetes progress to a stage that cannot be modified by functional manoeuvres, indicating a switch towards predominantly organic dysfunction. METHODS: We studied 117 patients with a short duration (8.9 ± 0.1 years) and 37 patients with a long duration (33.7 ± 0.5 years) of type 1 diabetes, 73 healthy controls and 12 heart-transplanted participants (surgical heart denervation). An autonomic score was calculated from autonomic function tests. Spectral analysis of heart rate and blood pressure variability, and BRS, were obtained from recordings during normal (15 breaths per min) and slow, deep (six breaths per min) controlled breathing. RESULTS: BRS was reduced in all patients, but more in patients with a long duration of diabetes or with increasing autonomic involvement, although the effect of duration disappeared after adjustment for age. Slow breathing increased the BRS to the level of the control participants at a normal rate of breathing (15 per min) in all patients except those with an abnormal autonomic score. CONCLUSIONS/INTERPRETATION: Patients with type 1 diabetes have a blunted BRS that in the majority of patients can be restored by slow breathing, irrespective of disease duration. Even after a long duration of diabetes, the abnormal BRS is at least in part of functional origin.

Early autonomic dysfunction in type 1 diabetes: a reversible disorder?

AIMS/HYPOTHESIS: Cardiac autonomic neuropathy is associated with increased morbidity and mortality rates in patients with type 1 diabetes. The prevalence of early autonomic abnormalities is relatively high compared with the frequency of manifest clinical abnormalities. Thus, early autonomic dysfunction could to some extent be functional and might lead to an organic disease in a subgroup of patients only. If this is true, manoeuvres such as slow deep-breathing, which can improve baroreflex sensitivity (BRS) in normal but not in denervated hearts, could also modify autonomic modulation in patients with type 1 diabetes, despite autonomic dysfunction. METHODS: We compared 116 type 1 diabetic patients with 36 matched healthy control participants and 12 heart-transplanted participants with surgically denervated hearts. Autonomic function tests and spectral analysis of heart rate and blood pressure variability were performed. BRS was estimated by four methods during controlled (15 breaths per minute) and slow deep-breathing (six breaths per minute), and in supine and standing positions. RESULTS: Conventional autonomic function tests were normal, but resting spectral variables and BRS were reduced during normal controlled breathing in patients with type 1 diabetes. However, slow deep-breathing improved BRS in patients with type 1 diabetes, but not in patients with surgically denervated hearts. Standing induced similar reductions in BRS in diabetic and control participants. CONCLUSIONS/INTERPRETATION: Although we found signs of increased sympathetic activity in patients with type 1 diabetes, we also observed a near normalisation of BRS with a simple functional test, indicating that early autonomic derangements are to a large extent functional and potentially correctable by appropriate interventions.

Lipid abnormalities predict progression of renal disease in patients with type 1 diabetes.

AIMS/HYPOTHESIS: We studied the impact of baseline lipid variables on the progression of renal disease in a large nationwide prospective cohort of patients with type 1 diabetes. METHODS: A total of 2,304 adult patients with type 1 diabetes and available lipid profiles participating in the Finnish Diabetic Nephropathy Study (FinnDiane) were evaluated. Data on progression of renal disease were verified from medical files and patients were followed for 5.4 +/- 2.0 (mean +/- SD) years. RESULTS: High triacylglycerol, apolipoprotein (Apo) B, ApoA-II and HDL(3)-cholesterol concentrations predicted incident microalbuminuria. Progression to macroalbuminuria was predicted by high triacylglycerol and ApoB. When AER was entered into the model, triacylglycerol was no longer an independent predictor, but when patients with normal AER and microalbuminuria at baseline were pooled, triacylglycerol, HbA(1c), male sex and AER were all independent predictors of renal disease. High total cholesterol, LDL-cholesterol, non-HDL-cholesterol and triacylglycerol as well as low HDL-cholesterol, HDL(2)-cholesterol, ApoA-I and ApoA-II concentrations were predictive of progression to end-stage renal disease. However, when estimated GFR was entered into the model, only total cholesterol remained an independent predictor of progression. CONCLUSIONS/INTERPRETATION: Lipid abnormalities, particularly high triacylglycerol concentrations, increase the risk of progression of renal disease.

Relationship between lipid profiles and kidney function in patients with type 1 diabetes.

AIMS/HYPOTHESIS: We studied the relationship between the lipid profile, estimated GFR (eGFR) and AER in patients with type 1 diabetes. We also assessed the association between the lipid profile and glycaemic control, obesity and hypertension in an environment free of manifest renal disease, as well as exploring how well the patients would have achieved the targets set in international guidelines. METHODS: A total of 2,927 adult patients who had type 1 diabetes and for whom lipid profiles were available were included from people participating in the nationwide, multicentre Finnish Diabetic Nephropathy Study (FinnDiane). eGFR was determined using the Cockcroft-Gault formula adjusted for body surface area. RESULTS: Patients with impaired renal function (eGFR <60 ml min(-1) 1.73 m(-2)) had higher total cholesterol, triacylglycerol and apolipoprotein B, and lower HDL-cholesterol concentrations than patients with normal renal function (eGFR >90 ml min(-1) 1.73 m(-2)) or mildly impaired renal function (eGFR 60-90 ml min(-1) 1.73 m(-2)) (p < 0.001 for all associations). In type 1 diabetic patients without manifest renal disease, similar adverse lipid profiles could be observed in those who were overweight or obese and in those who had intermediate or poor glycaemic control or hypertension. In all the different patient groups 14 to 43% would have achieved the recommended target of <2.6 mmol/l for LDL-cholesterol. CONCLUSIONS/INTERPRETATION: Multiple lipid abnormalities are not only present in type 1 diabetic patients with an abnormal AER, but also in those with impaired renal function. In patients without manifest renal disease, obesity, glycaemic control or hypertension were associated with an adverse lipid profile. A substantial number of patients studied would have exceeded the targets set by international guidelines, particularly the targets for LDL-cholesterol.