Dynamic associations between glucose and ecological momentary cognition in Type 1 Diabetes.

Type 1 diabetes (T1D) is a chronic condition characterized by glucose fluctuations. Laboratory studies suggest that cognition is reduced when glucose is very low (hypoglycemia) and very high (hyperglycemia). Until recently, technological limitations prevented researchers from understanding how naturally-occurring glucose fluctuations impact cognitive fluctuations. This study leveraged advances in continuous glucose monitoring (CGM) and cognitive ecological momentary assessment (EMA) to characterize dynamic, within-person associations between glucose and cognition in naturalistic environments. Using CGM and EMA, we obtained intensive longitudinal measurements of glucose and cognition (processing speed, sustained attention) in 200 adults with T1D. First, we used hierarchical Bayesian modeling to estimate dynamic, within-person associations between glucose and cognition. Consistent with laboratory studies, we hypothesized that cognitive performance would be reduced at low and high glucose, reflecting cognitive vulnerability to glucose fluctuations. Second, we used data-driven lasso regression to identify clinical characteristics that predicted individual differences in cognitive vulnerability to glucose fluctuations. Large glucose fluctuations were associated with slower and less accurate processing speed, although slight glucose elevations (relative to person-level means) were associated with faster processing speed. Glucose fluctuations were not related to sustained attention. Seven clinical characteristics predicted individual differences in cognitive vulnerability to glucose fluctuations: age, time in hypoglycemia, lifetime severe hypoglycemic events, microvascular complications, glucose variability, fatigue, and neck circumference. Results establish the impact of glucose on processing speed in naturalistic environments, suggest that minimizing glucose fluctuations is important for optimizing processing speed, and identify several clinical characteristics that may exacerbate cognitive vulnerability to glucose fluctuations.

Two for one? Effects of a couples intervention on partners of persons with Type 2 diabetes: a randomized controlled trial.

AIMS: To compare the outcomes of partners who participated in a telephone couples behavioural intervention to improve glycaemic control in persons with Type 2 diabetes with those of untreated partners of participants in an individual intervention or education; to explore 'ripple effects', i.e. positive behaviour changes seen in untreated partners. METHODS: The Diabetes Support Project was a three-arm randomized telephone intervention trial comparing outcomes of couples calls (CC), individual calls (IC) and diabetes education calls (DE). Couples included one partner with Type 2 diabetes and HbA1c ≥ 58 mmol/mol (7.5%). All arms received self-management education (two calls). CC and IC arms participated in 10 additional behaviour change calls. CC included partners, emphasizing partner communication, collaboration and support. Blinded assessments were performed at 4, 8 and 12 months. Partner outcomes were psychosocial (diabetes distress, relationship satisfaction, depressive symptoms), medical (BMI, blood pressure) and behavioural (fat intake, activity). RESULTS: Partners' (N = 268) mean age was 55.8 years, 64.6% were female and 29.9% were from minority ethnic groups. CC (vs. IC and DE) partners had greater reductions in diabetes distress, greater increases in marital satisfaction (4 and 8 months), and some improvements in diastolic BP. There were no consistent differences among arms in other outcomes. There was no evidence of a dietary or activity behaviour ripple effect on untreated partners, i.e. comparing partners in the IC and DE arms. CONCLUSIONS: A collaborative couples intervention resulted in significant improvements in partner diabetes distress and relationship satisfaction. There were no consistent effects on behavioural or medical partner outcomes, and no evidence of diet or activity behaviour ripple effects, suggesting that partners should be targeted directly to achieve these changes. (Clinical Trial Registry No: NCT01017523).

Safety and efficacy of once-weekly dulaglutide versus sitagliptin after 2 years in metformin-treated patients with type 2 diabetes (AWARD-5): a randomized, phase III study.

AIMS: To compare the once-weekly glucagon-like peptide-1 (GLP-1) receptor dulaglutide with the dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin after 104 weeks of treatment. METHODS: This AWARD-5 study was a multicentre, double-blind trial that randomized participants to dulaglutide (1.5 or 0.75 mg) or sitagliptin 100 mg for 104 weeks or placebo (reported separately) for 26 weeks. Change in glycated haemoglobin (HbA1c) concentration from baseline was the primary efficacy measure. A total of 1098 participants with HbA1c concentrations ≥7.0% (≥53.0 mmol/mol) and ≤9.5% (≤80.3 mmol/mol) were randomized, and 657 (59.8%) completed the study. We report results for dulaglutide and sitagliptin at the final endpoint. RESULTS: Changes in HbA1c at 104 weeks were (least squares mean ± standard error) -0.99 ± 0.06% (-10.82 ± 0.66 mmol/mol), -0.71 ± 0.07% (-7.76 ± 0.77 mmol/mol) and -0.32 ± 0.06% (-3.50 ± 0.66 mmol/mol) for dulaglutide 1.5 mg, dulaglutide 0.75 mg and sitagliptin, respectively (p < 0.001, both dulaglutide doses vs sitagliptin). Weight loss was greater with dulaglutide 1.5 mg (p < 0.001) and similar with 0.75 mg versus sitagliptin (2.88 ± 0.25, 2.39 ± 0.26 and 1.75 ± 0.25 kg, respectively). Gastrointestinal adverse events were more common with dulaglutide 1.5 and 0.75 mg versus sitagliptin (nausea 17 and 15% vs 7%, diarrhoea 16 and 12% vs 6%, vomiting 14 and 8% vs 4% respectively). Pancreatic, thyroid, cardiovascular and hypersensitivity safety were similar across groups. CONCLUSIONS: Dulaglutide doses provided superior glycaemic control and dulaglutide 1.5 mg resulted in greater weight reduction versus sitagliptin at 104 weeks, with acceptable safety.

Bone quality assessment in type 2 diabetes mellitus.

UNLABELLED: The increased risk for fractures in type 2 diabetes mellitus (T2DM) despite higher average bone density is unexplained. This study assessed trabecular bone quality in T2DM using the trabecular bone score (TBS). The salient findings are that TBS is decreased in T2DM and low TBS associates with worse glycemic control. INTRODUCTION: Type 2 diabetes mellitus is a risk factor for osteoporotic fractures despite high average bone mineral density (BMD). The aim of this study was to compare BMD with a noninvasive assessment of trabecular microarchitecture, TBS, in women with T2DM. METHODS: In a cross-sectional study, trabecular microarchitecture was examined in 57 women with T2DM and 43 women without diabetes, ages 30 to 90 years. Lumbar spine BMD was measured by dual-emission x-ray absorptiometry (DXA), and TBS was calculated by examining pixel variations within the DXA images utilizing TBS iNsight software. RESULTS: Mean TBS was lower in T2DM (1.228 ± 0.140 vs. 1.298 ± 0.132, p = 0.013), irrespective of age. Mean BMD was higher in T2DM (1.150 ± 0.172 vs. 1.051 ± 0.125, p = 0.001). Within the T2DM group, TBS was higher (1.254 ± 0.148) in subjects with good glycemic control (A1c ≤ 7.5 %) compared to those (1.166 ± 0.094; p = 0.01) with poor glycemic control (A1c > 7.5 %). CONCLUSION: In T2DM, TBS is lower and associated with poor glycemic control. Abnormal trabecular microarchitecture may help explain the paradox of increased fractures at a higher BMD in T2DM. Further studies are needed to better understand the relationship between glycemic control and trabecular bone quality.

Satiety, but not total PYY, Is increased with continuous and intermittent exercise.

OBJECTIVE: This study determined the hormonal and subjective appetite responses to exercise (1-h continuous versus intermittent exercise throughout the day) in obese individuals. DESIGN AND METHODS: Eleven obese subjects (>30 kg/m(2) ) underwent three 12-h study days: control condition [sedentary behavior (SED)], continuous exercise condition [(EX) 1-h exercise], and intermittent exercise condition [(INT) 12 hourly, 5-min bouts]. Blood samples (every 10 min) were measured for serum insulin and total peptide YY (PYY) concentrations, with ratings of appetite (visual analog scale [VAS): every 20 min]. Both total area under the curve (AUC), and subjective appetite ratings were calculated. RESULTS: No differences were observed in total PYY AUC between conditions, but hunger was reduced with INT (INT < EX; P < 0.05), and satiety was increased with both SED and INT conditions (INT > EX and SED > EX; P < 0.05). A correlation existed between the change in total PYY and insulin levels (r = -0.81; P < 0.05), and total PYY and satiety (r = 0.80; P < 0.05) with the EX condition, not the SED and INT conditions. CONCLUSIONS: The total PYY response to meals is not altered over the course of a 12-h day with either intermittent or continuous exercise; however, intermittent exercise increased satiety and reduced hunger to a greater extent than continuous exercise in obese individuals.

Improved diabetes control in the elderly delays global cognitive decline.

OBJECTIVES: To examine whether improved diabetes control is related to better cognitive outcomes. DESIGN: Randomized control trial. SETTING: A randomized trial of telemedicine vs. usual care in elderly persons with type 2 diabetes. PARTICIPANTS: Participants were 2169 persons 55 years and older with type 2 diabetes from New York City and Upstate New York. INTERVENTION: The diabetes case management intervention was implemented by a diabetes nurse, via a telemedicine unit in the participant's home, and in coordination with the primary care physician. MEASUREMENTS: Hemoglobin A1c (HbA1c), systolic blood pressure (SBP), and low density lipoprotein cholesterol (LDL), were measured at a baseline visit and at up to 5 annual follow-up visits. Global cognition was measured at those visits with the Comprehensive Assessment and Referral Evaluation (CARE). RESULT: In mixed models the intervention was related to slower global cognitive decline in the intervention group (p = 0.01). Improvements in HbA1c (p = 0.03), but not SBP or LDL, mediated the effect of the intervention on cognitive decline. CONCLUSION: Improved diabetes control in the elderly following existing guidelines through a telemedicine intervention was associated with less global cognitive decline. The main mediator of this effect seemed to be improvements in HbA1c.

Plasticity of heart rate signalling and complexity with exercise training in obese individuals with and without type 2 diabetes.

OBJECTIVE: To examine the responsiveness of cardiac autonomic function and baroreflex sensitivity (BRS) to exercise training in obese individuals without (OB) and with type 2 diabetes (ObT2D). DESIGN: Subjects were tested in the supine position and in response to a sympathetic challenge before and after a 16-week aerobic training program. All testing was conducted in the morning following a 12-h fast. SUBJECTS: A total of 34 OB and 22 ObT2D men and women (40-60 years of age) were studied. MEASUREMENTS: Heart rate variability (HRV) was measured at rest via continuous ECG (spectral analysis with the autoregressive approach) and in response to upright tilt. The dynamics of heart rate complexity were analyzed with sample entropy and Lempel-Ziv entropy, and BRS was determined via the sequence technique. Subjects were aerobically trained 4 times per week for 30-45 min for 16 weeks. RESULTS: Resting HR decreased and total power (lnTP, ms(2)) of HRV increased in response to exercise training (P<0.05). High frequency power (lnHF) increased in OB subjects but not in OBT2D, and no changes occurred in ln low frequency/HF power with training. Upright tilt decreased lnTP and lnHF and increased LF/HF (P<0.01) but there were no group differences in the magnitude of these changes nor were they altered with training in either group. Tilt also decreased complexity (sample entropy and Lempel-Ziv entropy; P<0.001), but there was no group or training effect on complexity. BRS decreased with upright tilt (P<0.01) but did not change with training. Compared to OB subjects the ObT2D had less tilt-induced changes in BRS. CONCLUSION: Exercise training improved HRV and parasympathetic modulation (lnHF) in OB subjects but not in ObT2D, indicating plasticity in the autonomic nervous system in response to this weight-neutral exercise program only in the absence of diabetes. HR complexity and BRS were not altered by 16 weeks of training in either OB or ObT2D individuals.

Short-term exercise training improves aerobic capacity with no change in arterial function in obesity.

The aim of the study is to determine the effects of short-term high-intensity exercise on arterial function and glucose tolerance in obese individuals with and without the metabolic syndrome (MetSyn). Obese men and women (BMI > 30 kg/m(2); 39-60 years) with and without MetSyn (MetSyn, n = 13; Non-MetSyn, n = 13) participated in exercise training consisting of ten consecutive days of treadmill walking for 1 h/day at 70-75% of peak aerobic capacity. Changes in aerobic capacity, flow-mediated dilation (FMD), and arterial stiffness using central and peripheral pulse wave velocity (PWV) measurements were assessed pre- and post-training. These measurements were obtained fasting and 1-h post-test meal while the subjects were hyperglycemic. Aerobic capacity improved for both groups [Non-MetSyn 24.0 +/- 1.6 vs. 25.1 +/- 1.5 mL/(kg min); MetSyn 25.2 +/- 1.8 vs. 26.2 +/- 1.7 mL/(kg min), P < 0.05]. There was no change in body weight. FMD decreased by ~20% (P < 0.05) for both groups during acute hyperglycemia (MetSyn, n = 11; Non-MetSyn, n = 10), while hyperglycemia increased central PWV and not peripheral PWV. Exercise training did not change FMD in the fasted or challenged state. Central and peripheral PWV were not altered with training for either group (MetSyn, n = 13; Non-MetSyn, n = 13). A 10-day high-intensity exercise program in obese individuals improved aerobic capacity and glucose tolerance but no change in arterial function was observed. Acute hyperglycemia had a deleterious effect on arterial function, suggesting that persons with impaired glucose homeostasis may experience more opportunities for attenuated arterial function on a daily basis which could contribute to increased cardiovascular risk.

Effect of ezetimibe/simvastatin compared with atorvastatin on lipoprotein subclasses in patients with type 2 diabetes and hypercholesterolaemia.

AIM: To evaluate the effects of the usual starting and next higher doses of ezetimibe/simvastatin and atorvastatin on the cholesterol content of lipoprotein subclasses in patients with type 2 diabetes and hypercholesterolaemia. METHODS: This post hoc analysis compared the effects of treatment with ezetimibe/simvastatin 10/20 mg vs. atorvastatin 10 and 20 mg/day and ezetimibe/simvastatin 10/40 mg/day vs. atorvastatin 40 mg/day on the cholesterol content of lipoprotein subclasses in the modified intent-to-treat (mITT) population (n = 1013) and in subgroups of patients with triglyceride (TG) levels <200 mg/dl (n = 600) and >or=200 mg/dl (2.6 mmol/l) (n = 413). RESULTS: Ezetimibe/simvastatin significantly reduced low-density lipoprotein cholesterol (LDL-C) subclasses LDL(1)-C, LDL(2)-C and LDL(3)-C; real LDL-C (LDL-C(r)); intermediate-density lipoprotein cholesterol (IDL-C), IDL(1)-C, IDL(2)-C; very low-density lipoprotein cholesterol (VLDL-C), VLDL(3)-C; and remnant-like lipoprotein cholesterol (RLP-C) from baseline more than atorvastatin at all dose comparisons (p < 0.01) in the mITT population. Significant improvements were also observed in high-density lipoprotein cholesterol (HDL-C) subclass HDL(3)-C at the ezetimibe/simvastatin 10/20 mg vs. atorvastatin 20 mg and highest dose comparisons (p < 0.001) and in VLDL(1 + 2)-C at the lowest and highest dose comparisons (p < 0.001). Changes in LDL(4)-C and LDL-C subclass patterns (A, B and I) were comparable for both treatments. Generally, similar results were observed for patients with TG levels <200 and >or=200 mg/dl (2.3 mmol). For both treatments, notable differences between TG subgroups were that patients with elevated TGs had smaller reductions in LDL(2)-C, slightly smaller decreases in all IDL subclasses and greater decreases in all VLDL-C subclasses than those with lower TG levels. Frequency of pattern B was also reduced more in patients with higher TGs for both treatments. CONCLUSIONS: Ezetimibe/simvastatin reduced the cholesterol content of most lipoprotein subclasses from baseline with generally similar efficacy in patients with low and high TGs. Despite the different mechanism of action of ezetimibe, the response to ezetimibe/simvastatin and atorvastatin treatment related to these lipoprotein subclasses was generally consistent with the overall effects of these therapies on the major lipid/lipoprotein classes. The clinical significance of these results awaits further study.

Exercise is required for visceral fat loss in postmenopausal women with type 2 diabetes.

This study examined the effects of aerobic exercise without weight loss, a hypocaloric high monounsaturated fat diet, and diet plus exercise (D+E) on total abdominal and visceral fat loss in obese postmenopausal women with type 2 diabetes. Thirty-three postmenopausal women (body mass index, 34.6 +/- 1.9 kg/m(2)) were assigned to one of three interventions: a hypocaloric high monounsaturated fat diet alone, exercise alone (EX), and D+E for 14 wk. Aerobic capacity, body composition, abdominal fat distribution (magnetic resonance imaging), glucose tolerance, and insulin sensitivity were measured pre- and postintervention. Body weight ( approximately 4.5 kg) and percent body fat ( approximately 5%) were decreased (P < 0.05) with the D and D+E intervention, whereas only percent body fat ( approximately 2.3%) decreased with EX. Total abdominal fat and sc adipose tissue (SAT) were reduced with the D and D+E interventions (P < 0.05), whereas visceral adipose tissue (VAT) decreased with the D+E and EX intervention, but not with the D intervention. EX resulted in a reduction in total abdominal fat, VAT, and SAT (P < 0.05) despite the lack of weight loss. The reductions in total abdominal fat and SAT explained 32.7% and 9.7%, respectively, of the variability in the changes in fasting glucose levels, whereas the reductions in VAT explained 15.9% of the changes in fasting insulin levels (P < 0.05). In conclusion, modest weight loss, through either D or D+E, resulted in similar improvements in total abdominal fat, SAT, and glycemic status in postmenopausal women with type 2 diabetes; however, the addition of exercise to diet is necessary for VAT loss. These data demonstrate the importance of exercise in the treatment of women with type 2 diabetes.

Influence of resistance exercise training on glucose control in women with type 2 diabetes.

The objective of the study was to evaluate the effects of acute and chronic resistance training on glucose and insulin responses to a glucose load in women with type 2 diabetes. Subjects consisted of type 2 diabetic women (n = 7) and age-matched controls (n = 8) with normal glucose tolerance. All subjects participated in 3 oral glucose tolerance tests: pretraining, 12 to 24 hours after the first exercise session (acute) and 60 to 72 hours after the final training session (chronic). Exercise training consisted of a whole body resistance exercise program using weight-lifting machines 3 days per week for 6 weeks. Resistance training was effective in increasing strength of all muscle groups in all subjects. Integrated glucose concentration expressed as area under the curve (AUC) was 3,355.0 +/- 324.6 mmol/L. min pretraining, improved significantly (P <.01) after the acute bout of exercise (2,868 +/- 324.0 mmol/L. min), but was not improved with chronic training (3,206.0 +/- 337.0 mmol/L. min) in diabetic subjects. A similar pattern of significance was observed with peak glucose concentration (pre: 20.2 +/-1.4 mmol/L; acute: 17.2 +/- 1.7 mmol/L; chronic: 19.9 +/- 1.7 mmol/L). There were no significant changes in insulin concentrations after any exercise bout in the diabetic subjects. There were no changes in glucose or insulin levels in control subjects. An acute bout of resistance exercise was effective in improving integrated glucose concentration, including reducing peak glucose concentrations in women with type 2 diabetes, but not age-matched controls. There were no significant changes in insulin concentrations for either group. Resistance exercise offers an alternative to aerobic exercise for improving glucose control in diabetic patients. To realize optimal glucose control benefits, individuals must follow a regular schedule that includes daily exercise.

Resting leptin responses to acute and chronic resistance training in type 2 diabetic men and women.

PURPOSE: To evaluate the plasma leptin levels approximately 24 h post-exercise in control and type 2 diabetic subjects and to establish if observed changes in leptin concentrations were acute or chronic effects of a resistance training program. METHODS: Thirty men and women (17 controls and 13 type 2, obese diabetics, age 40-55 y) had resting blood samples drawn at 08:00 h (12 h postprandial) at the beginning of the study (pre-training), 24 h after a three repetition maximal weight lifting bout (acute) and 72 h after their last training bout of 6 weeks of resistance training (chronic). The two groups were not matched with respect to body mass index and the control subjects were not normal weight. Subjects weight-trained three times a week, for 6 weeks, for 1 h, training both the upper and lower body. RESULTS: Serum leptin concentrations were significantly higher in the type 2 diabetics than in the control group at pre-training (41.4+/-8.9 vs 11.4+/-3.0 ng/ml, P<0.05, respectively). Compared to pre-training, the leptin levels decreased significantly (P<0.01) after acute exercise in the diabetics but not in the control subjects (diabetics 30.9+/-7.1 vs controls 10.6+/-2.6 ng/ml). Approximately 72 h after 6 weeks of exercise training, the leptin concentrations were no longer lower than the pre-training values in either group (36.9+/-8.8 vs 11.9+/-8.8 ng/ml, respectively, P=NS). When leptin concentrations were log transformed and adjusted for fat mass there were still significant changes in leptin levels over time and between the control and diabetic group (P<0.05). CONCLUSIONS: The type 2 diabetics showed a significant 30% reduction in resting leptin levels 24 h after a single bout of resistance exercise. This was an acute response to resistance exercise and not a chronic training effect (no difference between pre-training and chronic). The decreased resting leptin concentrations approximately 24 h post-acute exercise may be due to reduced glucose availability to the adipose tissue, particularly in the diabetic subjects. There is no chronic effect of resistance exercise on leptin concentrations.

Abdominal fat distribution in pre- and postmenopausal women: The impact of physical activity, age, and menopausal status.

Age-related increases in total body fat have been reported, but the impact of menopause on abdominal fat distribution is still unclear. The purpose of this study was to determine the impact of menopausal status on abdominal fat distribution using magnetic resonance imaging (MRI). In addition, we investigated the influence of abdominal fat distribution on blood lipid profiles and leptin concentrations. Twenty-three premenopausal (PRE), 27 postmenopausal (POST), and 28 postmenopausal women on estrogen replacement therapy (ERT) had measurements of regional abdominal fat, blood lipids, and serum leptin concentrations. The women were matched for body mass index (BMI) and total body fat mass. Age and menopausal status were not found to be significant predictors of total abdominal fat, visceral fat, or subcutaneous fat, while physical activity was a significant predictor (P <.01) for total abdominal fat (R(2) =.16), visceral fat (R(2) =.32) and percent visceral fat (R(2) =.25). There was a trend for a greater visceral fat content in the POST women compared with the PRE women (2,495.0 +/- 228.4 v 1,770.4 +/- 240.8 cm(2), respectively, P =.06). The percent visceral abdominal fat was significantly lower (P <.05) in the premenopausal women than in either postmenopausal group (PRE, 23.2% +/- 1.7%; POST, 28.9% +/- 1.8%; ERT, 28.9% +/- 1.6%). Menopausal status and age did not influence any of the blood lipid values. Abdominal fat distribution was a significant predictor of cholesterol concentrations and the cholesterol/high-density lipoprotein-cholesterol (HDL-C) ratio, but only accounted for approximately 15% of the variability in these levels. Total body fat and physical activity accounted for 47% of the variability in leptin concentrations, while abdominal fat distribution, age, and menopausal status were not significant predictors. In conclusion, in early postmenopausal women, the level of physical activity accounts for the variability in abdominal fat distribution observed, while menopausal status and age do not play a significant role. ERT was not associated with additional benefits in abdominal fat distribution compared with postmenopausal women not on ERT or in the blood lipid profile in these women.

The marital relationship and psychosocial adaptation and glycemic control of individuals with diabetes.

OBJECTIVE: To explore the relationship between marital relationship domains (i.e., intimacy and adjustment) and glycemic control and psychosocial adaptation to diabetes. RESEARCH DESIGN AND METHODS: A total of 78 insulin-treated adults with both type 1 and type 2 diabetes were assessed on a single occasion. They completed two marital quality measures (Spanier Dyadic Adjustment Scale and Personal Assessment of Intimacy in Relationships Scale) and four quality-of-life measures (Diabetes Quality of Life Scale, Medical Outcomes Study Health Survey, Problem Areas in Diabetes Scale, and Positive and Negative Affect Scale). Glycemic control was assessed by HbA(1c). Demographic data (age, sex, type and duration of diabetes, years married, other medical conditions, family history, disability, and years of education) were gathered from the chart and questionnaires. RESULTS: Concerning psychosocial adaptation, both of the marital quality measures were predictors of aspects of adaptation. Better marital satisfaction was related to higher levels of diabetes-related satisfaction and less impact, as well as less diabetes-related distress and better general quality of life. Higher levels of marital intimacy were related to better diabetes-specific and general quality of life. Concerning glycemic control, there was a nonsignificant trend for marital adjustment scores to relate to HbA(1c) (P = 0.0568). CONCLUSIONS: For insulin-treated adults with diabetes, quality of marriage is associated with adaptation to diabetes and other aspects of health-related quality of life. The suggestive finding that marital adjustment may relate to glycemic control warrants further study. Future work should also explore the impact of couples-focused interventions on adaptation, adherence, and glycemic control.

Central diabetes insipidus due to herpes simplex in a patient immunosuppressed by Cushing's syndrome.

OBJECTIVE: To describe a patient immunocompromised by Cushing's syndrome in whom central diabetes insipidus developed as a complication of herpes simplex involvement of the hypothalamus. METHODS: We present a case, including results of laboratory and histopathologic studies, in which herpes simplex was established as the causative agent for central diabetes insipidus. RESULTS: A woman with ectopic corticotropin-dependent Cushing's syndrome, diabetes mellitus, carcinoid tumor, and a history of thyroid cancer had the precipitous onset of seizure and fever, and hypotonic polyuria and progressive hypernatremia developed. Central diabetes insipidus was diagnosed and successfully treated with desmopressin. Nevertheless, the patient's condition deteriorated and she died. Autopsy revealed herpes simplex encephalitis involving the magnicellular neurons of the hypothalamus. CONCLUSION: Central diabetes insipidus caused by viral infections has been reported in immunosuppressed patients, such as those with acquired immunodeficiency syndrome (AIDS). To our knowledge, this is the first report of a herpes infection causing diabetes insipidus in a patient immunosuppressed by Cushing's syndrome. This case demonstrates that, in patients with Cushing's syndrome, diabetes insipidus may develop as a result of herpes simplex infection of the hypothalamus.

Impact of the work environment on glycemic control and adaptation to diabetes.

OBJECTIVE: To evaluate quantitatively whether the work environments of adults with diabetes relate to the adequacy of metabolic control and/or to the individual's adaptation to diabetes and to explore qualitatively the interactions between an individual's life at work and ways of coping with diabetes. RESEARCH DESIGN AND METHODS: A total of 129 insulin-requiring adults who were employed outside of the home were assessed on a single occasion. They completed two work system measures (The Work Environment Scale and The Work Apgar Scale) and two quality-of-life measures (The Diabetes Quality of Life Scale and The Appraisal of Diabetes Scale). Subjects also participated in a semi-structured interview concerning the interaction of work and diabetes. Glycemic control was assessed by using HbAlc results. Demographic data (age, sex, diabetes type, duration of diabetes, number of diabetes-related medical complications) were gathered from the charts. RESULTS: Concerning glycemic control, neither of the work system measures was a significant predictor of HbAlc. Concerning psychosocial adaptation, supervisor support was found to be a significant predictor of positive appraisal and diabetes-related satisfaction. Involvement and coworker cohesion also predicted aspects of diabetes-related quality of life. Interview themes showed that for a minority (18%), diabetes affected choice of work and that for a majority (60%), diabetes affected relationships at work and raised financial/job concerns (49%). Most adjust their diet, blood glucose testing, and exercise regimen through work-related modifications. CONCLUSIONS: For insulin-treated adults with diabetes, work system variables do not directly relate to glycemic control, but they do relate to psychosocial adaptation. Future work should examine further the specific aspects of the workplace that might affect adaptation, with the goal being to develop worksite interventions that target not only the employee with diabetes but also their supervisors and coworkers.

Diet and exercise in the treatment of obesity: effects of 3 interventions on insulin resistance.

BACKGROUND: In short-term studies, diet and exercise both improve insulin sensitivity. OBJECTIVE: To determine the effects of a 48-week supervised diet and exercise program on weight and insulin sensitivity after initial weight loss and weight maintenance, and then subsequent weight regain over 96 weeks. METHODS: Forty-five obese women were randomly assigned to 1 of 3 treatment groups: (1) diet alone, (2) diet and aerobic training, and (3) diet and strength training. All subjects received the same 48-week group behavior modification program and diet (approximately 3879 kJ/d [approximately 925 kcal/d] for the first 16 weeks; approximately 6276 kJ/d [approximately 1500 kca/d] thereafter). Exercising subjects were provided 3 supervised exercise sessions per week for the first 28 weeks and 2 sessions weekly until week 48. During weeks 48 to 96, subjects were unsupervised. Oral glucose tolerance tests were performed at baseline and weeks 16, 24, 44, and 96. RESULTS: Subjects across the 3 conditions achieved a mean weight loss of 13.8 kg by week 16, which was associated with decreased insulin levels (61.8% of baseline) There were no significant differences among groups in changes in body mass index, which is a measure of weight in kilograms divided by the square of the height in meters, weight, glucose tolerance, or insulin levels at weeks 16, 24, and 44. No additional beneficial effect of aerobic or strength exercise on insulin resistance, as reflected by serum insulin levels before and after a glucose load, was demonstrated. The 22 subjects who were studied at week 96 maintained a loss of approximately 10% of initial weight. Insulin levels, however, had returned to pretreatment levels. CONCLUSIONS: This study confirms the beneficial effect of weight reduction on hyperinsulinemia in obese individuals. Participation in supervised exercise did not result in additional improvement in weight loss or insulin sensitivity. We also observed a marked increase in insulin levels with only partial weight regain. Determining the amount of sustained weight loss necessary for continued improvement in insulin sensitivity will require further study.

Translocation of PKC delta by insulin in a rat hepatoma cell line.

The aim of this study was to examine the effects of insulin and phorbol 12-myristate 13-acetate (PMA), an activator of classic and novel PKCs, on the translocation of PKC from cytosol to membrane in H4IIE (H4) rat hepatoma cells. Six PKC isoforms were expressed, including PKC-mu and PKC-lambda, identified for the first time in this hepatoma-cell line. Insulin induced translocation of PKC-delta from the cytosol to the membrane fraction as early as 15 min and maximally at 60 min with levels returning to that of controls by 180 min. Insulin also decreased levels of PKC-zeta in membranes at 5, 10, 15, and 30 min, but had no effect on cytosol levels. Ten minutes of PMA treatment translocated PKC-delta completely, and 24 h of PMA treatment downregulated PKC-delta. Neither acute nor chronic PMA had any effect on PKC-zeta. These studies establish the ability of both insulin and PMA to activate PKC-delta in H4 cells, and coupled with our previous work demonstrating a diminution of the effect of insulin on gene transcription in PKC downregulated cells, suggest that insulin may exert specific effects, in part, through a PKC-dependent pathway.