James D. Lane

Depressed mood is a factor in glycemic control in type 1 diabetes.

Objective The diabetes literature contains conflicting evidence on the relationship between depression and glycemic control. This may be due, in part, to the fact that past studies failed to distinguish between patients with type 1 and type 2 diabetes. Because these are actually completely different diseases that are often treated differently and consequently make different demands on patients, the relationship between glycemic control and depressed mood in type 1 and type 2 diabetes was examined separately. Methods The relationship between Beck Depression Inventory (BDI) scores and HbA1c, as an index of long-term glycemic control, was measured in samples of 30 patients with type 1 and 34 patients with type 2 diabetes. Results Groups of patients with type 1 and type 2 diabetes did not differ in mean BDI score or HbA1c level. Correlation analysis revealed a significant positive relationship between BDI scores and HbA1c in the type 1 group (r = .44, p < .02) but not in the type 2 group (r = −0.06, p > .05). This relationship was evident throughout the entire range of BDI scores and was not restricted to scores indicative of clinical depression. Patients with type 1 diabetes who had higher HbA1c and BDI scores reported a lower frequency of home blood glucose monitoring. Conclusions Variations in depressive mood, below the level of clinical depression, are associated with meaningful differences in glycemic control in type 1 but not type 2 diabetes. Preliminary data analysis suggests that this effect may be mediated, at least in part, by decreased self-care behaviors in patients with more depressed mood.

Caffeine effects on cardiovascular and neuroendocrine responses to acute psychosocial stress and their relationship to level of habitual caffeine consumption.

&NA; The effects of a moderate dose of caffeine on cardiovascular and neuroendocrine stress reactivity were examined in 25 healthy male subjects selected as habitual or light consumers of caffeine. Measurements were taken under resting conditions before and after administration of caffeine (3.5 mg/kg) or placebo, during a stressful laboratory task, and in a post‐stress recovery period. Caffeine elevated blood pressure and plasma norepinephrine levels at rest, effects which added significantly to the effects of stress. Caffeine potentiated stress‐related increases in plasma epinephrine and cortisol stress, more than doubling the responses observed in the control condition. These effects were present in both habitual and light consumers and level of habitual caffeine consumption did not affect their magnitude. Results indicate that caffeine can potentiate both cardiovascular and neuroendocrine stress reactivity and that the habitual use of caffeine is not necessarily associated with the development of tolerance to these effects.

Menstrual cycle effects on caffeine elimination in the human female

SummaryIncreases in the levels of sex steroids due to pregnancy or oral contraceptive steroid use are known to decrease significantly the rate at which caffeine is eliminated from the body. An investigation has now been made into whether the changes in sex steroid levels that occur during normal menstrual cycling also affect the rate of caffeine elimination, especially whether hormonal shifts in the luteal phase are associated with slower elimination of caffeine. Repeated 24-hour caffeine elimination studies were conducted during the follicular and luteal phases of the menstrual cycle in 10 healthy women.Comparisons of the follicular and luteal phases revealed that systemic clearance of caffeine was slower in the luteal phase, although the t1,2 did not differ. The slowing effect was related to the proximity to onset of menstruation and to levels of progesterone.The evidence suggests that caffeine elimination may be slowed in the late luteal phase, prior to the onset of menstruation. Such a reduction would lead to increased accumulation of caffeine with repeated self-administration during the day, but the effect may be too small to be of clinical significance in the majority of women.

Racial differences in blood pressure and forearm vascular responses to the cold face stimulus.

&NA; The mechanisms responsible for the higher incidence of essential hypertension in blacks than in whites are the object of much research attention. One hypothesis is that the development of hypertension in blacks is associated with exaggerated blood pressure reactivity, particularly those responses mediated by vasoconstriction. Racial differences in blood pressure responses to cold stimulation of the forehead, a known alpha‐adrenergic vasoconstrictive stimulus, were examined in health, college‐age males. Compared to white subjects, black subjects exhibited significantly greater increases in systolic and diastolic blood pressure, as well as increases in forearm vascular resistance, in response to cold stimulation. This preliminary evidence of increased peripheral vascular reactivity in blacks suggests that known racial differences in hypertension prevalence might derive in part from physiological differences in sympathetic nervous system reactivity.

Binaural Auditory Beats Affect Vigilance Performance and Mood

When two tones of slightly different frequency are presented separately to the left and right ears the listener perceives a single tone that varies in amplitude at a frequency equal to the frequency difference between the two tones, a perceptual phenomenon known as the binaural auditory beat. Anecdotal reports suggest that binaural auditory beats within the electroencephalograph frequency range can entrain EEG activity and may affect states of consciousness, although few scientific studies have been published. This study compared the effects of binaural auditory beats in the EEG beta and EEG theta/delta frequency ranges on mood and on performance of a vigilance task to investigate their effects on subjective and objective measures of arousal. Participants (n = 29) performed a 30-min visual vigilance task on three different days while listening to pink noise containing simple tones or binaural beats either in the beta range (16 and 24 Hz) or the theta/delta range (1.5 and 4 Hz). However, participants were kept blind to the presence of binaural beats to control expectation effects. Presentation of beta-frequency binaural beats yielded more correct target detections and fewer false alarms than presentation of theta/delta frequency binaural beats. In addition, the beta-frequency beats were associated with less negative mood. Results suggest that the presentation of binaural auditory beats can affect psychomotor performance and mood. This technology may have applications for the control of attention and arousal and the enhancement of human performance.

Changes in depressive symptoms and glycemic control in diabetes mellitus.

Objective: To investigate if changes in depressive symptoms would be associated with changes in glycemic control over a 12-month period in patients with Type 1 and Type 2 diabetes. Methods: Ninety (Type 1 diabetes, n = 28; Type 2 diabetes, n = 62) patients having Beck Depression Inventory (BDI) levels of >10 were enrolled in the study. Of those 90 patients, 65 patients completed a 12-week cognitive behavioral therapy intervention. BDI was assessed at baseline and thereafter biweekly during 12 months. Hemoglobin (HbA1c) and fasting blood glucose levels were assessed at baseline and at four quarterly in-hospital follow-up visits. Linear mixed-model analysis was applied to determine the effects of time and diabetes type on depressive symptoms, HbA1c levels, and fasting glucose levels. Results: Mean and standard deviation baseline BDI and HbA1c levels were 17.9 ± 5.8 and 7.6 ± 1.6, respectively, with no significant difference between patients with Type 1 and Type 2 diabetes. Mixed-model regression analysis found no difference between the groups with Type 1 and Type 2 diabetes in the within-subject effect of BDI score on HbA1c or fasting glucose levels during the study. Depressive symptoms decreased significantly (p = .0001) and similarly over a 12-month period in both patients with Type 1 and Type 2 diabetes, whereas HbA1c and fasting glucose levels did not change significantly over time in either group. Conclusion: Changes in depressive symptoms were not associated with changes in HbA1c or fasting glucose levels over a 1-year period in either patients with Type 1 or Type 2 diabetes. CBT = cognitive behavioral therapy; BDI = Beck Depression Inventory; BMI = body mass index; HAM-D = Hamilton depression scale.

Modification of Postprandial Hyperglycemia With Insulin Lispro Improves Glucose Control in Patients With Type 2 Diabetes

OBJECTIVE Insulin lispro is a rapid-acting analog of human insulin that can be used to target the postprandial rise in plasma glucose. We designed an open-label randomized crossover study of type 2 diabetic patients with secondary failure of sulfonylurea therapy to determine whether improvement of postprandial hyperglycemia would affect total daily glucose control. RESEARCH DESIGN AND METHODS Twenty-five type 2 diabetic patients who were poorly controlled on a maximum dose of sulfonylureas were studied in a university hospital clinical research center. In one arm of the study, patients continued therapy with maximum-dose sulfonylureas. In the other arm, patients used a combination therapy with insulin lispro before meals and sulfonylureas. After 4 months, patients were crossed over to the opposite arm. Fasting plasma glucose (FPG) and 1- and 2-h postprandial glucose (after a standardized meal), HbA1c, total, HDL, and LDL cholesterol, and triglyceride levels were measured at the end of each arm of the study. RESULTS Insulin lispro in combination with sulfonylurea therapy significantly reduced 2-h postprandial glucose concentrations compared with sulfonylureas alone, from 18.6 to 14.2 mmol/l (P < 0.0001), and incremental postprandial glucose area from 617.8 to 472.9 mmol · min · 1−1 (P < 0.0007). FPG levels were decreased from 10.9 to 8.5 mmol/l (P < 0.0001), and HbA1c values were reduced form 9.0 to 7.1% (P < 0.0001). Total cholesterol was significantly decreased in the lispro arm from 5.44 to 5.10 mmol/l (P < 0.02). HDL cholesterol concentrations were increased in the lispro arm from 0.88 to 0.96 mmol/l (P < 0.01). The patients weighed significantly more after lispro therapy than after sulfonylureas alone, but the difference was small in absolute terms (sulfonylurea therapy alone, 90.6 kg; lispro therapy, 93.8 kg; P < 0.0001). Two episodes of hypoglycemia (glucose concentrations, < 2.8 mmol/l) were reported by the patients while using lispro. CONCLUSIONS Previously, it has not been possible to address the effect of treatment of postprandial hyperglycemia specifically. We have now shown that the treatment of postprandial hyperglycemia with insulin lispro markedly improves overall glucose control and some lipid parameters in patients with type 2 diabetes.

Individual differences in smoking reward from de-nicotinized cigarettes

Most studies of cigarette smoking and smoking cessation have focused on the psychopharmacological effects of nicotine; relatively few have explored the role of sensory aspects of cigarette smoke. Sensory aspects of cigarette smoke play a role in the maintenance of smoking behavior, and may be particularly important for certain smokers. This paper presents the results of a pooled analysis of nine studies conducted in our laboratory, in order to explore the influence of demographic and smoking-related variables on ratings of de-nicotinized as compared to nicotine-containing cigarettes. A major finding of this analysis is that ratings of smoking derived from de-nicotinized, but not nicotine-containing, cigarettes appear to vary with level of tobacco dependence, suggesting that sensory factors may be more important to highly dependent, as compared to less-dependent, smokers. The implications of these findings for smoking cessation treatment and for future research are discussed.

Childhood socioeconomic status and serotonin transporter gene polymorphism enhance cardiovascular reactivity to mental stress.

Objective: To test the hypothesis that low socioeconomic status (SES) and the 5HTTLPR L allele are associated with increased cardiovascular reactivity (CVR) to stress in a larger sample and that SES and 5HTTLPR genotypes interact to enhance CVR to stress. CVR to mental stress has been proposed as one mechanism linking stress to the pathogenesis of cardiovascular disease. The more transcriptionally efficient long (L) allele of a polymorphism of the serotonin transporter gene promoter (5HTTLPR) has been found associated with increased risk of myocardial infarction. We found the long allele associated with larger CVR to mental stress in a preliminary study of 54 normal volunteers. Methods: Subjects included 165 normal community volunteers stratified for race, gender, and SES, who underwent mental stress testing. Results: Childhood SES as indexed by Father’s Education Level was associated with larger systolic blood pressure (SBP) (p < .05) and diastolic blood pressure (DBP) (p = .01) responses to mental stress. The L allele was associated with larger SBP (p = .04), DBP (p < .0001), and heart rate (p = .04) responses to mental stress compared with the short (S) allele. Subjects with the SS genotype and high Father’s Education exhibited smaller SBP (5.2 mm Hg) and DBP (2.9 mm Hg) responses than subjects with LL genotype and low Father’s Education (SBP = 13.3 mm Hg, p = .002; DBP = 9.7 mm Hg, p < .0001). Conclusions: Both the 5HTTLPR long allele and low SES, particularly during childhood, are associated with increased CVR to mental stress, which could account, at least in part, for the increased cardiovascular disease risk associated with these characteristics. If confirmed in further research, these characteristics could be used to identify persons who might benefit from preventive interventions. CVD = cardiovascular disease; CVR = cardiovascular reactivity; 5HTTLPR = serotonin transporter promoter polymorphism; SBP = systolic blood pressure; DBP = diastolic blood pressure; HR = heart rate; SES = socioeconomic status; GCRC = General Clinical Research Center; CNS = central nervous system.

Caffeine and cardiovascular responses to stress.

Caffeine and psychologic stress have similar physiologic effects. Moderate doses of caffeine were found to elevate blood pressure in healthy, young males during periods of rest and stress. Blood pressure during stress was also significantly higher after caffeine had been consumed. The elevation of blood pressure due to caffeine appears to add to that elicited by stress. The implications of these results for prevention and treatment of cardiovascular disease are discussed.