Fasting plasma glucose variability as a marker of nocturnal hypoglycemia in diabetes: Evidence from the PREDICTIVE™ study

The relationship between fasting glucose (FG) variability and nocturnal hypoglycemia was assessed using longitudinal data from PREDICTIVE™, the large-scale observational study of insulin detemir. An HbA_1c-corrected correlation was found between these endpoints, suggesting FG variability can serve as a useful marker for this risk in clinical practice.     

Assessment of CPR interruptions from transthoracic impedance during use of the LUCAS™ mechanical chest compression system

BackgroundQuality of cardiopulmonary resuscitation (CPR) is a key determinant of outcome following out-of-hospital cardiac arrest (OHCA). Recent evidence shows manual chest compressions are typically too shallow, interruptions are frequent and prolonged, and incomplete release between compressions is common. Mechanical chest compression systems have been developed as adjuncts for CPR but interruption of CPR during their use is not well documented.AimAnalyze interruptions of CPR during application and use of the LUCAS? chest compression system.Methods54 LUCAS 1 devices operated on compressed air, deployed in 3 major US emergency medical services systems, were used to treat patients with OHCA. Electrocardiogram and transthoracic impedance data from defibrillator/monitors were analyzed to evaluate timing of CPR. Separately, providers estimated their CPR interruption time during application of LUCAS, for comparison to measured application time.ResultsIn the 32 cases analyzed, compressions were paused a median of 32.5 s (IQR 25–61) to apply LUCAS. Providers’ estimates correlated poorly with measured pause length; pauses were often more than twice as long as estimated. The average device compression rate was 104/min (SD 4) and the average compression fraction (percent of time compressions were occurring) during mechanical CPR was 0.88 (SD 0.09).ConclusionsInterruptions in chest compressions to apply LUCAS can be <20 s but are often much longer, and users do not perceive pause time accurately. Therefore, we recommend better training on application technique, and implementation of systems using impedance data to give users objective feedback on their mechanical chest compression device use.     

Power spectral analysis of heart rate variability during hyperinsulinemia in nondiabetic offspring of type 2 diabetic patients: evidence for possible early autonomic dysfunction in insulin-resistant subjects.

Sympathetic activation has been considered as a link between insulin resistance, hyperinsulinemia, and hypertension. However, little is known about the association between insulin sensitivity and autonomic regulation or about the effect of acute hyperinsulinemia on cardiac sympathovagal balance. The aim of this study was to investigate heart rate variability (HRV) during the euglycemic-hyperinsulinemic clamp in nondiabetic offspring of patients with type 2 diabetes. We studied 35 nondiabetic offspring of patients with type 2 diabetes and 19 control subjects. Probands were chosen from a 10-year follow-up study of patients with well-characterized type 2 diabetes according to their fasting C-peptide level (selected from both ends of the distribution) and from control subjects to form three groups: 1) a group including subjects who were offspring of type 2 diabetic patients with low C-peptide levels (deficient insulin secretion group [IS group], n = 17), 2) a group including subjects who were offspring of type 2 diabetic patients with high C-peptide levels (insulin-resistant group [IR group], n = 18), and 3) a control group without a history of type 2 diabetes in first-degree relatives (n = 19). HRV was assessed at baseline and at the steady state during the euglycemic-hyperinsulinemic clamp. Rates of whole-body glucose uptake (M value) were lower in the IR group than in the IS group and the control group (41+/-3 vs. 54+/-2 vs. 60+/-4 micromol x kg(-1) x min(-1), P < 0.01 and P < 0.01, respectively). In all groups, heart rate increased significantly during hyperinsulinemia. In the IR group, insulin infusion increased total power of HRV [from 7.70+/-0.15 to 8.05+/-0.15 ln(ms2), P < 0.01] and the low frequency-to-high frequency ratio (from 0.62+/-0.14 to 1.14+/-0.18, P < 0.01) and decreased power of the high frequency spectral component (from 5.73+/-0.17 to 5.43+/-0.16 ln(ms2), P < 0.05), whereas in other groups, changes in HRV were not significant. We conclude that the HRV response to acute hyperinsulinemia in the offspring of type 2 diabetic probands was likely to be modulated by the type 2 diabetic phenotype of the parent. In insulin-resistant subjects, autonomic dysfunction may be an earlier defect than hitherto acknowledged.     

Cultured allogeneic skin cells are effective in the treatment of chronic diabetic leg and foot ulcers.

Diabetic ulcers on the lower extremities present a difficult treatment problem, and some ulcers respond poorly to conventional topical and cast treatment. The purpose of this study was to assess the effect of cultured allogeneic keratinocyte epithelium and fibroblast-gelatin sponge on the healing of chronic, refractory diabetic leg and foot ulcers. Non-diabetic chronic leg ulcers were treated for comparison. This open study comprised 22 patients with type I or type II diabetes and 16 patients with leg or ankle ulcers of different aetiologies. A total of 26 diabetic and 25 non-diabetic ulcers were treated mainly with keratinocyte epithelium and/or fibroblast-gelatin sponge once weekly until complete healing or until no further healing could be observed despite several repeated treatments. The duration of diabetic ulcers was 10.3+/-15.8 (mean+/-SD) months and the size 3.1+/-6.6 cm2. The diabetic ulcers were located in the heel (7), toe (7), sole (5), leg (6) and Achilles (1). The mean duration of non-diabetic ulcers was 6.8+/-6.0 months and the size 10.5+/-11.8 cm2. A total of 12+/-11 skin cell transplantations were performed for the diabetic ulcers. All but 1 diabetic ulcer healed during the study. The time for 50% reduction in ulcer area was 32+/-32 days, but 99+/-110 days were needed for complete ulcer closure. The longer the ulcer had existed the longer was the healing time. Heel ulcers showed significantly slower healing response than leg, sole and toe ulcers. Preliminary results suggest that both keratinocytes and fibroblasts are equally effective in the healing process. The time required for healing of the diabetic ulcers did not differ markedly from that of the non-diabetic ulcers. The results suggest that cultured allogeneic skin cells used once weekly are effective in the treatment of recalcitrant diabetic ulcers.     

Serum cortisol and inflammatory response in neutropenic fever

There are no data on serum cortisol of hematological patients at the onset of neutropenic fever and its possible association with the severity of infection. The purpose of this study was to evaluate the association of serum cortisol with the level of C-reactive protein (CRP) and procalcitonin (PCT), widely used markers of infection and inflammation, and with the development of severe sepsis in this patient group. All clinical data were collected prospectively at the hematology ward of Kuopio University Hospital. Altogether, 69 hematological patients with 93 periods of neutropenic fever were included. Nineteen patients received therapy for acute myeloid leukemia, and 50 patients were autologous stem cell transplantation recipients. Each period of neutropenic fever was classified as severe sepsis or not. Serum cortisol, CRP, and PCT were determined at the onset of fever on day 0 and then at 8–9 a.m. on days 1–4. Level of serum cortisol correlated positively with maximal CRP level during days 0 to 4 in neutropenic fever periods without severe sepsis, but no correlation was observed in fever periods with severe sepsis. To conclude, the level of cortisol correlated with the severity of infection measured as maximal CRP or elevated PCT in fever periods without severe sepsis, but in fever periods with severe sepsis, the cortisol response was attenuated.     

Short- and intermediate-interval cortical inhibition and facilitation assessed by navigated transcranial magnetic stimulation

One of the most widely utilized in vitro models of ischemia or oxygen glucose deprivation (OGD) is the hippocampal organotypical culture (HOTC). The HOTC is used not only for the study of the mechanisms of cell death, but also has been the cornerstone of synaptic physiology. Although the intact nature of the HOTC is one of its primary advantages, some studies require a dissociated preparation in order to distinguish cell type specific responses. Typically, primary dissociated neuronal cultures are prepared from embryonic tissue. Since the HOTC is prepared from postnatal pups, we wanted to establish a primary culture of hippocampus from postnatal pups to parallel our studies in the HOTC preparation. Mixed cultures were prepared by enzymatic dissociation of hippocampus from 7-day-old mouse pups. These cultures responded to OGD with a time course of delayed cell death that was similar to that reported in HOTC. Dual label immunocytochemical staining revealed that neurons, but not astrocytes, were dying from apoptosis following OGD. To examine this vulnerability further, we also prepared neuronal enriched cultures by treating mixed cultures with cytosine-β-d-arabinofuranoside (CBA). These neuronal cultures appear to be even more sensitive to OGD. In addition, we have established primary astrocyte-enriched cultures from the same age pups to examine the vulnerability of astrocytes to OGD. These three culture preparations are useful for comparison of the responses of the two major cell types in the same culture, and the enriched cultures will allow biochemical, electrophysiological and molecular studies of homogenous cell populations.     

Cardiometabolic profile of people screened for high risk of type 2 diabetes in a national diabetes prevention programme (FIN-D2D)

AimsTo study screening of high-risk individuals as part of a national diabetes prevention programme in primary health care settings in Finland between 2003 and 2007, and evaluate the cardiometabolic risk profile of persons identified for intervention.MethodsHigh-risk individuals were identified by the Finnish Diabetes Risk Score (FINDRISC), history of impaired fasting glucose (IFG), impaired glucose tolerance (IGT), cardiovascular disease (CVD), or gestational diabetes. Participants subsequently underwent an oral glucose tolerance test. CVD morbidity risk was estimated by the Framingham Study Risk Equation and CVD mortality risk by the Systematic Coronary Risk Evaluation Formula (SCORE).ResultsA high-risk cohort of 10,149 (of whom 30.3% men) was identified (mean age 54.7 for men, 53.0 for women). Altogether 18.8% of men and 11.5% of women had screen-detected diabetes. In total 68.1% of men and 49.4% of women had abnormal glucose tolerance (IFG, IGT or screen-detected diabetes). Furthermore, 43.2% and 41.5% of men, and 13.3% and 11.3% of women, respectively, had a high predicted risk of CVD morbidity or mortality.ConclusionPrevalence of dysglycemia including undiagnosed diabetes and the predicted risk for CVD was alarmly high in the identified high-risk cohort, particularly in men.