Hypoglycemic thalamic activation in type 1 diabetes is associated with preserved symptoms despite reduced epinephrine.

Brain responses to low plasma glucose may be key to understanding the behaviors that prevent severe hypoglycemia in type 1 diabetes. This study investigated the impact of long duration, hypoglycemia aware type 1 diabetes on cerebral blood flow responses to hypoglycemia. Three-dimensional pseudo-continuous arterial spin labeling magnetic resonance imaging was performed in 15 individuals with type 1 diabetes and 15 non-diabetic controls during a two-step hyperinsulinemic glucose clamp. Symptom, hormone, global cerebral blood flow and regional cerebral blood flow responses to hypoglycemia were measured. Epinephrine release during hypoglycemia was attenuated in type 1 diabetes, but symptom score rose comparably in both groups. A rise in global cerebral blood flow did not differ between groups. Regional cerebral blood flow increased in the thalamus and fell in the hippocampus and temporal cortex in both groups. Type 1 diabetes demonstrated lesser anterior cingulate cortex activation; however, this difference did not survive correction for multiple comparisons. Thalamic cerebral blood flow change correlated with autonomic symptoms, and anterior cingulate cortex cerebral blood flow change correlated with epinephrine response across groups. The thalamus may thus be involved in symptom responses to hypoglycemia, independent of epinephrine action, while anterior cingulate cortex activation may be linked to counterregulation. Activation of these regions may have a role in hypoglycemia awareness and avoidance of problematic hypoglycemia.

Bone Health Index and bone turnover in pediatric patients with type 1 diabetes mellitus and poor metabolic control.

BACKGROUND: There is a need for a non-invasive, affordable, and reliable method for bone health screening in pediatric patients at risk. OBJECTIVE: To assess Bone Health Index (BHI) in pediatric patients with type 1 diabetes (T1D) and its relation to bone metabolism, age at onset, duration, control, and insulin dose. SUBJECTS AND METHODS: Left-hand radiographs were obtained from 65 patients with T1D, mean age 11.23 ± 3.89 years, mean disease duration 5.23 ± 3.76 years and mean glycosylated hemoglobin (HbA1c)-83 mmol/mol (9.7%). Blood and 24 hours urine samples were collected for bone and mineral metabolism assessment. BoneXpert was used to determine BHI, Bone Health Index standard deviation score (BHI SDS), and bone age. RESULTS: Mean BHI SDS was -1.15 ± 1.19 (n = 54). In 20.37% (n = 11) BHI SDS was < -2SD with mean value -2.82 ± 0. 69, P < .001. These patients had lower levels of beta cross laps (0.77 ± 0.33 ng/mL vs 1.17 ± 0.47 ng/mL), osteocalcin (47.20 ± 14.07 ng/mL vs 75.91 ± 32.08 ng/mL), serum magnesium (0.79 ± 0.05 mmol/L vs 0.83 ± 0.06 mmol/L) and phosphorus (1.48 ± 0.29 mmol/L vs 1.71 ± 0.28 mmol/L) but higher ionized calcium (1.29 ± 0.04 mmol/L vs 1.26 ± 0.05 mmol/L), P < .05, compared to patients with BHI SDS in the normal range. We found a positive correlation between BHI SDS and age at manifestation (r = 0.307, P = 0.024) and a negative one with disease duration (r = -0.284, P = .038). No correlations were found with HbA1c, insulin dose, height, weight, BMI. CONCLUSIONS: To the best of our knowledge, this is the first study to assess bone health in pediatric patients with T1D using BHI. We found significantly decreased cortical bone density and bone turnover in 20.37%. Earlier age at onset and diabetes duration may have a negative impact on cortical bone density in patients with poor control. Longitudinal studies are needed to follow changes or to assess future interventions.

Impaired skin microcirculation in paediatric patients with type 1 diabetes mellitus.

AIMS/HYPOTHESIS: We used Laser Doppler Fluximetry (LDF) to define "normal" endothelial function in a large cohort of healthy children and adolescents and to evaluate skin microcirculation in paediatric patients with type 1 diabetes mellitus. METHODS: LDF was performed in 102 healthy children (12.8 ± 3.3 years of age; 48 male) and 68 patients (12.9 ± 3.3 years of age; 33 male). Duration of disease was 5.0 ± 3.97 years. Each participant sequentially underwent three stimulation protocols (localized thermal hyperaemia with localized warming to maximum 40°C, iontophoretic delivery of pilocarpine hydrochloride (PCH) and sodium nitroprusside (SNP)). The maximum relative increase in skin blood flow and the total relative response, i.e. the area under the curve (AUC) to each stimulus (AUCheat, AUCPCH, AUCSNP) was determined. In addition, the area of a right-angled triangle summarizing the time to and the amplitude of the first peak, which represents the axon reflex mediated neurogenic vasodilation (ARR) was calculated. RESULTS: In healthy controls, AUCheat, AUCPCH, AUCSNP, and ARR turned out to be independent of sex, age, and anthropometric values. Per parameter the 10th percentile generated from data of healthy controls was used as the lower threshold to define normal endothelial function. Diabetic patients showed significantly reduced vasodilatative response to either physical or pharmacological stimulation with SNP, whereas the response to PCH was comparable in both cohorts. In patients compared to controls i) a significantly higher frequency of impaired vasodilatation in response to heat and SNP was noted and ii) vascular response was classified as pathological in more than one of the parameters with significantly higher frequency. CONCLUSIONS/INTERPRETATION: Skin microvascular endothelial dysfunction is already present in about 25% of paediatric type 1 diabetic patients suffering from type 1 diabetes for at least one year. Future studies are needed to assess the predictive value of endothelial dysfunction in the development of long-term (cardio)vascular comorbidity in these patients.

Two weeks taurine supplementation reverses endothelial dysfunction in young male type 1 diabetics.

Type 1 diabetics have a well-recognised risk of accelerated cardiovascular disease. Even in the absence of clinical signs there are detectable abnormalities of conduit vessel function. Our group has previously reported reversal of endothelial dysfunction in diabetics with pravastatin. In young asymptomatic smokers, taurine supplementation has a beneficial impact on macrovascular function, assessed by FMD, and shows an up-regulation of nitric oxide from monocyte-endothelial cell interactions. We hypothesise that taurine supplementation reverses early endothelial abnormalities in young male type 1 diabetics, as assessed by applanation tonometry, brachial artery ultrasound and laser Doppler fluximetry. Asymptomatic, male diabetics (n=9) were scanned prior to treatment and then randomised in a double-blind cross-over fashion to receive either 2 weeks placebo or taurine. Control patients (n=10) underwent a baseline scan. Assessed diabetics had detectable, statistically significant abnormalities when compared with controls, in both arterial stiffness (augmentation index) and brachial artery reactivity (FMD). Both of these parameters were returned to control levels with 2 weeks taurine supplementation. In conclusion, 2 weeks taurine supplementation reverses early, detectable conduit vessel abnormalities in young male diabetics. This may have important implications in the long-term treatment of diabetic patients and their subsequent progression towards atherosclerotic disease.