Autonomic and peripheral nerve function in early diabetic neuropathy. Possible influence of a novel aldose reductase inhibitor on autonomic function

Autonomic and peripheral nerve functions as well as the possible short-term effect of a novel aldose reductase inhibitor (ARI) on neuropathy were evaluated in 30 male type I diabetics (age 25-44 years, mean 34; duration of diabetes 10-20 years, mean 34) with neurographic signs of peripheral neuropathy (PN). Autonomic neuropathy (AN) was established by the heart rate reactions to deep breathing (E/I ratio = vagal function) and to tilt (acceleration index = sympathetic and vagal functions; the brake index = vagal function). Twenty-nine patients, 13 with AN, completed the study. Among neurographic variables, only sural nerve function tests correlated with autonomic functions. Patients with AN showed significantly lower mean sensory action potential amplitudes (SAPA) sural, indicating axonal losses, than patients without AN (3.58 +/- 0.79 microV v. 7.34 +/- 1.12 microV; p less than 0.01). PN as measured by neurography did not improve during ARI treatment. On the other hand, vagal function (brake indices) improved (p less than 0.05) during ARI in AN patients.     

Glucose and leucine kinetics in idiopathic ketotic hypoglycaemia.

AIMS: To investigate glucose and leucine kinetics in association with metabolic and endocrine investigations in children with ketotic hypoglycaemia (KH) in order to elucidate the underlying pathophysiology. METHODS: Prospective interventional study using stable isotope tracer in nine children (mean age 4.23 years, range 0.9-9.8 years; seven males) with KH and 11 controls (mean age 4.57 years, range 0.16-12.3 years; four males). RESULTS: Plasma insulin levels were significantly lower in KH compared to subjects in the non-KH group. Plasma ketone body levels were significantly higher in KH than in non-KH. Basal metabolic rate was significantly higher in subjects with KH (45.48+/-7.41 v 31.81+/-6.72 kcal/kg/day) but the respiratory quotients were similar in both groups (KH v non-KH, 0.84+/-0.05 v 0.8+/-0.04. Leucine oxidation rates were significantly lower in children with KH (12.25+/-6.25 v 31.96+/-8.59 micromol/kg/h). Hepatic glucose production rates were also significantly lower in KH (3.84+/-0.46 v 6.6+/-0.59 mg/kg/min). CONCLUSIONS: KH is caused by a failure to sustain hepatic glucose production rather than by increased glucose oxidation rates. Energy demand is significantly increased, whereas leucine oxidation is reduced.     

Irreversible progression of severe retinopathy in young type I insulin-dependent diabetes mellitus patients after improved metabolic control.

The impact of metabolic control on the development of rapidly progressive severe retinopathy was studied in 14 young type I insulin-dependent diabetes mellitus (IDDM) patients. Glycosylated hemoglobin (HbAlc) levels 45 months prior to and 12 months after the diagnosis of retinopathy were compared with HbAlc levels in 17 type I IDDM patients with no or minimal background retinopathy, matched for age and duration of diabetes. HbAlc levels were generally higher in patients with severe retinopathy (p less than 0.05) from 39 months until 6 months before the diagnosis of retinopathy. Thereafter, there was a gradual decrease in HbAlc levels reaching the same level as in control patients 6 months after diagnosis of retinopathy. Patients with severe retinopathy required higher doses of insulin prior to the diagnosis of retinopathy (p less than 0.05), but the insulin requirement decreased, and 12 months afterward, the insulin dosage was similar to patients with background retinopathy. Systolic blood pressure levels were slightly increased and higher in patients with severe retinopathy compared with control patients from 18 months before to diagnosis of retinopathy (p less than 0.05). Diastolic blood pressure levels likewise differed at 18 and 12 months before and at the time of diagnosis of retinopathy as well as 12 months afterward (p less than 0.05); however, no differences were seen in urinary albumin or serum creatinine levels between the groups. Thus, years of poor metabolic control, drastically improved, preceded the development of irreversible severe retinopathy in these young type I IDDM patients.     

Circulating anti-pericyte autoantibodies are present in Type 2 diabetic patients and are associated with non-proliferative retinopathy

AIMS/HYPOTHESIS: This study aims to determine the prevalence of anti-pericyte autoantibodies in Type 2 diabetes and to characterize these autoantibodies as new markers of disease activity in diabetic retinopathy. METHODS: A total of 299 patients with Type 2 diabetes participated in this study. Retinopathy was assessed by 7-field stereo fundus photography and was graded according to the ETDRS scale. Serum anti-pericyte autoantibodies were detected by immunofluorescence on tissue cultured bovine retinal pericytes. RESULTS: The prevalence of anti-pericyte autoantibodies in Type 2 diabetic patients was 54% and was approximately equal in men and women. The prevalence was approximately 55% with retinopathy at grades from 10 to 53. At grades above 53 the prevalence declined to 23% ( p<0.0001). The highest prevalence by duration of diabetes, 70%, was found at 0 to 5 years and the lowest, 25% at more than 25 years duration ( p<0.0001). CONCLUSION/INTERPRETATION: Anti-pericyte autoantibodies are present at high prevalence in Type 2 diabetes. Their presence during earlier stages of retinopathy could be due to a reaction with antigens expressed by "activated" pericytes. The decline in antibody prevalence in advanced retinopathy could mark pericyte loss and progression to an angiogenic retinal milieu.     

Traumatic aortic and mitral valve injury following blunt chest injury with a variable clinical course

Blunt trauma is uncommonly followed by intracardiac valvar injuries. The resulting valvar insufficiency rapidly or progressively leads to congestive heart failure or death unless surgically corrected. Three patients with sustained blunt chest trauma were found to have two aortic valve and one mitral valve ruptures. They had variable clinical courses. However, after the diagnosis was established, surgical intervention was attempted promptly, which consisted of two aortic valve replacements and one mitral valvoplasty. Their postoperative courses were uneventful. Careful observation and repeated physical examination, aided by echocardiography, were required after the blunt chest trauma.     

Test–retest variability for standard automated perimetry and short‐wavelength automated perimetry in diabetic patients

Purpose: To assess limits for significant improvement or deterioration of visual fields in diabetic patients based on short‐term test–retest variability in subjects with different degrees of retinopathy. Methods: Fifty patients with diabetic retinopathy ranging from level 10 to 75 [according to the Early Treatment Diabetic Retinopathy Study (ETDRS) severity scale] were tested repeatedly with both standard automated perimetry (SAP) and short‐wavelength automated perimetry (SWAP) with short intervals. The association between visual field loss and degree of retinopathy outside fovea was analysed. Test–retest variability of global and local visual field indices and prediction limits for significant change were calculated. Results: The amount of visual field loss was significantly associated to the degree of retinopathy, with a correlation coefficient of ?0.51 for SAP (P = 0.0003) and ?0.45 for SWAP (P = 0.002). Global test–retest variability was smaller with SAP than with SWAP (P < 0.0001). For both SAP and SWAP, local test–retest variability was considerably smaller at test points with normal sensitivity than at test points with reduced sensitivity (P < 0.0001). Paracentral test points within 10° of eccentricity had less variability than peripheral points (P < 0.0001), implying that smaller change is required to reach statistically significant improvement or deterioration at initially normal and paracentral points than at depressed points and peripherally located test points. Conclusion: Our results propose that SAP, as well as SWAP, can be useful for monitoring visual function outside fovea in diabetic patients with various degrees of retinopathy. We report a preference for SAP because of less variability generally. Limits for significant improvement or deterioration have been assessed but need future validation in a longitudinal study.     

High levels of cortisol among adolescent offspring of parents with bipolar disorder: a pilot study

The hypothalamic-pituitary-adrenal (HPA) axis is compromised at several levels in major depressive and bipolar disorder (BD). However, it is not known whether HPA abnormalities predate the onset of these disorders. We conducted a pilot study comparing salivary cortisol levels of 10 adolescent offspring of parents with BD and 10 offspring of parents with no mental disorder (NMD). For two days, samples were collected at awakening and during the day in the adolescents' natural environment. The offspring of parents with BD had higher mean cortisol levels in the mornings and afternoons than the offspring of parents with NMD. When controlling for age, group differences in cortisol persisted in the afternoon, but not morning samples. None of the adolescents met diagnostic criteria for anxiety, affective, attention-deficit, or conduct disorders. Although preliminary, the results suggest that there is an early abnormality in the HPA system of the offspring of parents with BD.     

Type 1 diabetes patients with severe non-proliferative retinopathy may benefit from panretinal photocoagulation

PURPOSE: To examine whether panretinal photocoagulation for severe non-proliferative retinopathy in type 1 diabetes patients could halt the progression of retinopathy with subsequent vitreous haemorrhages and visual impairment. METHODS: During a 10-year follow-up study period of 344 type 1 diabetes patients, 81 subjects went through panretinal photocoagulation. Forty patients were treated for severe non-proliferative retinopathy (age at onset of diabetes 14 +/- 8 years, diabetes duration 18 + 10 years) and 41 for proliferative retinopathy (age at onset 15 +/- 10 years, diabetes duration 22 + 13 years). One randomly selected eye per patient forms the basis for the study. Metabolic control, systolic and diastolic blood pressure, serum creatinine and urinary albumin levels were measured and analysed yearly during the follow-up period. RESULTS: A total of 35% (14/40) of eyes treated for severe non-proliferative retinopathy developed neovascularizations during a mean time of 2.9 +/- 1.5 years. Vitreous haemorrhages were more frequent in eyes with proliferative retinopathy at treatment than in eyes with severe non-proliferative retinopathy (12/41 versus 2/40; p = 0.007). The number of vitrectomies due to vitreous haemorrhages in eyes treated for severe non-proliferative retinopathy tended to be lower (1/40 versus 6/41; p = 0.052). Before photocoagulation, visual acuity (VA) was similar in eyes with severe non-proliferative retinopathy and in those with proliferative retinopathy (1.0, 0.4-1.0 versus 1.0, 0.1-1.0; median and range). Visual impairment and blindness tended to develop more often in eyes treated for proliferative retinopathy compared to those treated for severe non-proliferative retinopathy (10/40 versus 4/40; p = 0.056). Eyes with neovascularizations at follow-up were more often visually impaired (VA < 0.5) than eyes without neovascularizations (15/55 versus 1/26; p = 0.016). CONCLUSION: In type 1 diabetes, panretinal photocoagulation may be beneficial even at the severe non-proliferative retinopathy stage in terms of preventing vitreous haemorrhage, subsequent vitrectomy and visual impairment.