Marlene Wewalka

Real-Time Continuous Glucose Monitoring in Critically Ill Patients: A prospective randomized trial

OBJECTIVE To evaluate the impact of real-time continuous glucose monitoring (CGM) on glycemic control and risk of hypoglycemia in critically ill patients. RESEARCH DESIGN AND METHODS A total 124 patients receiving mechanical ventilation were randomly assigned to the real-time CGM group (n = 63; glucose values given every 5 min) or to the control group (n = 61; selective arterial glucose measurements according to an algorithm; simultaneously blinded CGM) for 72 h. Insulin infusion rates were guided according to the same algorithm in both groups. The primary end point was percentage of time at a glucose level <110 mg/dl. Secondary end points were mean glucose levels and rate of severe hypoglycemia (<40 mg/dl). RESULTS Percentage of time at a glucose level <110 mg/dl (59.0 ± 20 vs. 55.0 ± 18% in the control group, P = 0.245) and the mean glucose level (106 ± 18 vs. 111 ± 10 mg/dl in the control group, P = 0.076) could not be improved using real-time CGM. The rate of severe hypoglycemia was lower in the real-time CGM group (1.6 vs. 11.5% in the control group, P = 0.031). CGM reduced the absolute risk of severe hypoglycemia by 9.9% (95% CI 1.2–18.6) with a number needed to treat of 10.1 (95% CI 5.4–83.3). CONCLUSIONS In critically ill patients, real-time CGM reduces hypoglycemic events but does not improve glycemic control compared with intensive insulin therapy guided by an algorithm.

Roux-en-Y Gastric Bypass Surgery or Lifestyle With Intensive Medical Management in Patients With Type 2 Diabetes: Feasibility and 1-Year Results of a Randomized Clinical Trial

IMPORTANCE Emerging data support bariatric surgery as a therapeutic strategy for management of type 2 diabetes mellitus. OBJECTIVE To test the feasibility of methods to conduct a larger multisite trial to determine the long-term effect of Roux-en-Y gastric bypass (RYGB) surgery compared with an intensive diabetes medical and weight management (Weight Achievement and Intensive Treatment [Why WAIT]) program for type 2 diabetes. DESIGN, SETTING, AND PARTICIPANTS A 1-year pragmatic randomized clinical trial was conducted in an academic medical institution. Participants included persons aged 21 to 65 years with type 2 diabetes diagnosed more than 1 year before the study; their body mass index was 30 to 42 (calculated as weight in kilograms divided by height in meters squared) and hemoglobin A1c (HbA1c) was greater than or equal to 6.5%. All participants were receiving antihyperglycemic medications. INTERVENTIONS RYGB (n = 19) or Why WAIT (n = 19) including 12 weekly multidisciplinary group lifestyle, medical, and educational sessions with monthly follow-up thereafter. MAIN OUTCOMES AND MEASURES Proportion of patients with fasting plasma glucose levels less than 126 mg/dL and HbA1c less than 6.5%, measures of cardiometabolic health, and patient-reported outcomes. RESULTS At 1 year, the proportion of patients achieving HbA1c below 6.5% and fasting glucose below 126 mg/dL was higher following RYGB than Why WAIT (58% vs 16%, respectively; P = .03). Other outcomes, including HbA1c, weight, waist circumference, fat mass, lean mass, blood pressure, and triglyceride levels, decreased and high-density lipoprotein cholesterol increased more after RYGB compared with Why WAIT. Improvement in cardiovascular risk scores was greater in the surgical group. At baseline the participants exhibited moderately low self-reported quality-of-life scores reflected by Short Form-36 total, physical health, and mental health, as well as high Impact of Weight on Quality of Life-Lite and Problem Areas in Diabetes health status scores. At 1 year, improvements in Short Form-36 physical and mental health scores and Problem Areas in Diabetes scores did not differ significantly between groups. The Impact of Weight on Quality of Life-Lite score improved more with RYGB and correlated with greater weight loss compared with Why WAIT. CONCLUSIONS AND RELEVANCE In obese patients with type 2 diabetes, RYGB produces greater weight loss and sustained improvements in HbA1c and cardiometabolic risk factors compared with medical management, with emergent differences over 1 year. Both treatments improve general quality-of-life measures, but RYGB provides greater improvement in the effect of weight on quality of life. These differences may help inform therapeutic decisions for diabetes and weight loss strategies in obese patients with type 2 diabetes until larger randomized trials are performed. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01073020.

Adjustable Gastric Band Surgery or Medical Management in Patients With Type 2 Diabetes: A Randomized Clinical Trial

CONTEXT Recommendations for surgical, compared with lifestyle and pharmacologically based, approaches for type 2 diabetes (T2D) management remain controversial. OBJECTIVE The objective was to compare laparoscopic adjustable gastric band (LAGB) to an intensive medical diabetes and weight management (IMWM) program for T2D. DESIGN This was designed as a prospective, randomized clinical trial. SETTING The setting was two Harvard Medical School-affiliated academic institutions. INTERVENTIONS AND PARTICIPANTS: A 12-month randomized trial comparing LAGB (n = 23) vs IMWM (n = 22) in persons aged 21-65 years with body mass index of 30-45 kg/m(2), T2D diagnosed more than 1 year earlier, and glycated hemoglobin (HbA(1c)) ≥ 6.5% on antihyperglycemic medication(s). MAIN OUTCOME MEASURE The proportion meeting the prespecified primary glycemic endpoint, defined as HbA(1c) < 6.5% and fasting glucose < 7.0 mmol/L at 12 months, on or off medication. RESULTS After randomization, five participants did not undergo the surgical intervention. Of the 40 initiating intervention (22 males/18 females; age, 51 ± 10 y; body mass index, 36.5 ± 3.7 kg/m(2); diabetes duration, 9 ± 5 y; HbA(1c), 8.2 ± 1.2%; 40% on insulin), the proportion meeting the primary glycemic endpoint was achieved in 33% of the LAGB patients and 23% of the IMWM patients (P = .457). HbA(1c) reduction was similar between groups at both 3 and 12 months (-1.2 ± 0.3 vs -1.0 ± 0.3%; P = .496). Weight loss was similar at 3 months but greater 12 months after LAGB (-13.5 ± 1.7 vs -8.5 ± 1.6 kg; P = .027). Systolic blood pressure reduction was greater after IMWM than LAGB, whereas changes in diastolic blood pressure, lipids, fitness, and cardiovascular risk scores were similar between groups. Patient-reported health status, assessed using the Short Form-36, Impact of Weight on Quality of Life, and Problem Areas in Diabetes, all improved similarly between groups. CONCLUSIONS LAGB and a multidisciplinary IMWM program have similar 1-year benefits on diabetes control, cardiometabolic risk, and patient satisfaction, which should be considered in the context of other factors, such as personal preference, when selecting treatment options with obese T2D patients. Longer duration studies are important to understand emergent differences.

Fasting Serum Taurine-Conjugated Bile Acids Are Elevated in Type 2 Diabetes and Do Not Change With Intensification of Insulin

CONTEXT Bile acids (BAs) are newly recognized signaling molecules in glucose and energy homeostasis. Differences in BA profiles with type 2 diabetes mellitus (T2D) remain incompletely understood. OBJECTIVE The objective of the study was to assess serum BA composition in impaired glucose-tolerant, T2D, and normal glucose-tolerant persons and to monitor the effects of improving glycemia on serum BA composition in T2D patients. DESIGN AND SETTING This was a cross-sectional cohort study in a general population (cohort 1) and nonrandomized intervention (cohort 2). PATIENTS AND INTERVENTIONS Ninety-nine volunteers underwent oral glucose tolerance testing, and 12 persons with T2D and hyperglycemia underwent 8 weeks of intensification of treatment. MAIN OUTCOME MEASURES Serum free BA and respective taurine and glycine conjugates were measured by HPLC tandem mass spectrometry. RESULTS Oral glucose tolerance testing identified 62 normal-, 25 impaired glucose-tolerant, and 12 T2D persons. Concentrations of total taurine-conjugated BA were higher in T2D and intermediate in impaired- compared with normal glucose-tolerant persons (P = .009). Univariate regression revealed a positive association between total taurine-BA and fasting glucose (R = 0.37, P < .001), postload glucose (R = 0.31, P < .002), hemoglobin A1c (R = 0.26, P < .001), fasting insulin (R = 0.21, P = .03), and homeostatic model assessment-estimated insulin resistance (R = 0.26, P = .01) and an inverse association with oral disposition index (R = -0.36, P < .001). Insulin-mediated glycemic improvement in T2D patients did not change fasting serum total BA or BA composition. CONCLUSION Fasting taurine-conjugated BA concentrations are higher in T2D and intermediate in impaired compared with normal glucose-tolerant persons and are associated with fasting and postload glucose. Serum BAs are not altered in T2D in response to improved glycemia. Further study may elucidate whether this pattern of taurine-BA conjugation can be targeted to provide novel therapeutic approaches to treat T2D.

Effects of Gastric Bypass and Gastric Banding on Bone Remodeling in Obese Patients With Type 2 Diabetes

CONTEXT Roux-en-Y gastric bypass (RYGB) leads to high-turnover bone loss, but little is known about skeletal effects of laparoscopic adjustable gastric banding (LAGB) or mechanisms underlying bone loss after bariatric surgery. OBJECTIVE To evaluate effects of RYGB and LAGB on fasting and postprandial indices of bone remodeling. DESIGN AND SETTING Ancillary investigation of a prospective study at 2 academic institutions. PARTICIPANTS Obese adults aged 21-65 years with type 2 diabetes who underwent RYGB (n = 11) or LAGB (n = 8). OUTCOMES Serum C-terminal telopeptide (CTX), procollagen type 1 N-terminal propeptide (P1NP), and PTH were measured during a mixed meal tolerance test at baseline, 10 days and 1 year after surgery. Changes in 25-hydroxyvitamin D, polypeptide YY (PYY), glucagon-like peptide-1, glucose-dependent insulinotropic peptide, and insulin were also assessed. RESULTS Fasting CTX increased 10 days after RYGB but not LAGB (+69 ± 23% vs +12±12%, P < .001), despite comparable weight loss at that time. By 1 year, fasting CTX and P1NP increased more after RYGB than LAGB (CTX +221 ± 60% vs +15 ± 6%, P<0.001; P1NP +93 ± 25% vs -9 ± 10%, P < .001) and weight loss was greater with RYGB. Changes in CTX were independent of PTH and 25-hydroxyvitamin D but were associated with increases in fasting PYY. Postprandial suppression of CTX was more pronounced after RYGB than LAGB at 10 days and 1 year postoperatively. CONCLUSIONS RYGB is accompanied by early increases in fasting indices of bone remodeling, independent of weight loss or changes in PTH or 25-hydroxyvitamin D. LAGB did not affect bone markers. PYY and other enterohormonal signals may play a role in RYGB-specific skeletal changes.

Gender-specific differences in energy metabolism during the initial phase of critical illness.

Background/objectives:Women and men differ in substrate and energy metabolism. Such differences may affect energy requirements during the acute phase of critical illness.Subjects/methods:Data of 155 critically ill medical patients were reviewed for this study. Indirect calorimetry in each patient was performed within the first 72 h following admission to the medical intensive care unit after an overnight fast.Results:In overweight (body mass index (BMI)⩾25 kg/m2) but not in normal-weight patients, resting energy expenditure (REE) adjusted for body weight (REEaBW) differed significantly between women and men (17.2 (interquartile range (IQR) 15.2–20.7) vs 20.9 (IQR 17.9–23.4) kcal/kg/day, P<0.01). Similarly, REE adjusted for ideal body weight (REEaIBW) was significantly lower in women compared with men (25.5 (IQR 22.6–28.1) vs 28.0 (IQR 25.2–30.0) kcal/kg/day, P<0.05). In overweight patients, gender was identified as an independent predictor of REEaBW in the multivariate regression model (r=−2.57 (95% CI −4.57 to −0.57); P<0.05), even after adjustment for age, simplified acute physiology score (SAPS II), body temperature, body weight and height.Conclusions:REEaBW decreases with increasing body mass in both sexes. This relationship differs between women and men. Overweight critically ill women show significantly lower REEaBW and REEaIBW, respectively, compared with men. These findings could affect the current practice of nutritional support during the early phase of critical illness.

Physical Activity in Obese Type 2 Diabetes After Gastric Bypass or Medical Management

BACKGROUND The purpose of this study was to compare effects of Roux-en-Y gastric bypass versus a multidisciplinary, group-based medical diabetes and weight management program on physical fitness and behaviors. METHODS Physical behavior and fitness were assessed in participants of the study Surgery or Lifestyle With Intensive Medical Management in the Treatment of Type 2 Diabetes (SLIMM-T2D) (NCT01073020), a randomized, parallel-group trial conducted at a US academic hospital and diabetes clinic with 18- to 24-month follow-up. Thirty-eight type 2 diabetes patients with hemoglobin A1c ≥6.5% and body mass index 30-42 kg/m2 were randomized to Roux-en-Y gastric bypass or the medical program. A 6-minute walk test to evaluate fitness, self-reported physical activity, standardized physical surveys, and cardiometabolic risk assessment were performed at baseline and after intervention. RESULTS Both groups similarly improved 6-minute walk test distance, with greater improvements in oxygen saturation and reduced heart rate after surgery. Self-reported physical activity improved similarly at 18-24 months after interventions, although exercise increased gradually after surgery, whereas early substantial increases in the medical group were not fully sustained. Self-reported total and physical health were similar by Short Form-36 but improved more in the Impact of Weight on Quality of Life survey after surgery. Improvement in cardiovascular risk scores, HbA1c, and body mass index were greater after surgery. CONCLUSION In this small, randomized study, both interventions led to therapeutic lifestyle changes and improved objective and self-reported physical fitness. Greater improvements in heart rate, oxygen saturation, and perceived impact of weight on health were seen after surgery, which could be attributable to greater weight loss. The clinical importance of these improvements with greater weight loss warrants further investigation.

Different enteral nutrition formulas have no effect on glucose homeostasis but on diet-induced thermogenesis in critically ill medical patients: a randomized controlled trial

Background/ObjectivesHyperglycemia is common in critically ill patients and associated with increased mortality. It has been suggested that different nutrition formulas may beneficially influence glucose levels in surgical intensive care patients. In this prospective randomized clinical cohort study we investigated glucose homeostasis in response to different enteral nutrition formulas in medical critically ill patients.Subjects/Methods60 medical critically ill patients were randomized to receive continuous fat-based (group A, n = 30) or glucose-based enteral nutrition (group B, n = 30) for seven days. Indirect calorimetry was performed to determine energy demand at baseline and on days 3 and 7. Glucose levels and area under the curve (AUC), insulin demand, glucose variability, and calorie and substrate intake per 24 h were assessed for 7 days.ResultsOver the course of 7 days patients had similar average daily glucose (p = 0.655), glucose AUC (A: 758 (641–829) mg/dl/day vs B: 780 (733–845) mg/dl/day, p = 0.283), similar overall insulin demand (A: 153.5 (45.3–281.5) IE vs B: 167.9 (82.3–283.8) IE, p = 0.525), and received similar amounts of enteral nutrition per 24 h. Resting energy expenditure was similar at baseline (A: 1556 (1227–1808) kcal/day vs B: 1563 (1306–1789) kcal/day, p = 0.882) but energy expenditure increased substantially over time in group A (p < 0.0001), but not in group B (p = 0.097).ConclusionFat-based and glucose-based EN influence glucose homeostasis and insulin demand similarly, yet diet-induced thermogenesis was substantially higher in critically ill patients receiving fat-based enteral nutrition.

Development of ARDS after Excessive Kath Consumption: A Case Report

Khat is a drug widely used in the Horn of Africa and the Arabian Peninsula. Khat leaves contain, among other substances, the psychoactive alkaloid cathinone, which induce central nervous system stimulation leading to euphoria, hyperactivity, restlessness, and insomnia. However, it also could cause psychological adverse effects such as lethargy, sleepiness, psychoses, and depression necessitating pharmacologic treatment. Here we report the case of a 35-year-old man from Somalia who became unconscious and developed aspiration pneumonia and subsequent ARDS after excessive consumption of khat leaves. His unconsciousness was possibly caused by the sleepiness developed after khat consumption and a benzodiazepine intake by the patient himself. Thus, khat-induced adverse effects should not primarily be treated pharmacologically, but patients should be urged to quit khat consumption in order to eliminate or, at least, reduce the severity of present psychological adverse effects.

Author’s reply to: Incorrect analyses were used in “Different enteral nutrition formulas have no effect on glucose homeostasis but on diet-induced thermogenesis in critically ill medical patients: a randomized controlled trial” and corrected analyses are requested

In our study, we evaluated the effect of fat-based (group A) or glucose-based (group B) enteral nutrition formulas on various parameters of glucose homeostasis in critically ill patients; however, both formulas seem to influence glucose levels and insulin demand similarly. Furthermore, we found a significant increase of resting energy expenditure (REE) over time in patients receiving fat-based enteral nutrition but not in patients receiving glucosebased formulas [1]. Dickinson et al. criticized that our conclusion “diet-induced thermogenesis was substantially higher in critically ill patients receiving fat-based enteral nutrition” was drawn from informal comparison of the nominal significance of change in each within-group comparison rather than a significance test of the difference in changes between the two groups [2]. Thus, we conducted the suggested additional statistical analyses. We evaluated differences in REE between both groups over time in a mixed model including diet, time points, and interaction between diet and time points as fixed effect and a random intercept for each patient. Significance of each estimated co-efficient in the model was calculated with t-statistics. Overall significance of discriminating between diet A and B over both follow up time points was calculated with Wald F test. The overall test for interaction between diet and time points was not significant (p= 0.1644). The estimated difference of the REE change until day 3 between the two groups (B–A) was −13.70 (95% CI:−193.47,166.07/p= 0.8811) and the estimated difference of the REE change until day 7 between the two groups (B–A) was −196.977 (95%CI:−407.98,14.04/p= 0.0708). Despite not reaching overall significance, there was a strong trend for an overall difference between groups until day 7. Our study was powered to detect differences of 20% in average glucose under different enteral nutrition formulas [3]. Therefore, it is likely that our sample size is too small to reach significance in this mixed model. Nonetheless, we are convinced that our conclusion concerning a secondary endpoint that diet-induced thermogenesis is higher in patients receiving fat-based enteral nutrition, can be drawn. We saw a substantial increase in REE only in patients fed with the fat-based formula (group A: baseline: 1556 (1227–1808) kcal/24 h vs. day 7: 1844 (1437–2018) kcal/ 24 h vs. group B: baseline 1563 (1306–1789) kcal/24 h vs. day 7: 1530 (1373–1871) kcal/24 h) and a strong trend (p= 0.07) of difference in change between groups over time in the mixed model. In addition, we would like to encourage to undertake further studies to validate our results in independent samples.