Clinical Practice Recommendations on the Routine Use of Eversense, the First Long-Term Implantable Continuous Glucose Monitoring System.

Background: The use of real-time continuous glucose monitoring (rtCGM) systems has proved to positively impact the management of type 1 diabetes with the potential to lower HbA1c, reduce frequency and time spent in hypoglycemia, and lower glycemic variability. Nevertheless, the acceptance of rtCGM remains below expectations and the dropout rate within the first year has been reported to be 27%. Besides financial reasons due to limited reimbursement, reasons include the need for frequent sensor replacement, the discomfort of wearing a sensor, the presence of adverse skin reactions, or privacy. Thus, novel approaches to rtCGM are desired to overcome these barriers. The first long-term implantable rtCGM system diversifies the field of glucose monitoring further. However, due to its novelty, there are no published clinical practice guidelines available. Aims: The aim of this article is to set the foundation for a best clinical practice for the everyday clinical care using a long-term implantable CGM system. Methods: An international expert panel for the long-term implantable CGM system developed this best practice guidance. All participants were certified and experienced in the use of the Eversense® long-term implantable CGM system. The workflows from the respective clinics were presented, discussed and are summarized in an ideal care workflow outlined in these practice recommendations. Results: The participants agreed on the following aspects: definition of the patient population that will benefit from a long-term implantable CGM device; real-world experience on safety and accuracy of a long-term CGM; definition of the ideal sensor position; description of the optimal process for sensor insertion, removal, and replacement.

Association between the preoperative fasting and postprandial C-peptide AUC with resolution of type 2 diabetes 6 months following bariatric surgery.

BACKGROUND AND AIMS: Bariatric surgery results in the remission of type 2 diabetes mellitus (T2DM) in morbidly obese subjects. The aim of the study was to investigate the predictive value of both static and dynamic measures of C-peptide in relation to T2DM resolution 6 months after bariatric surgery regardless of the operation type. METHODS AND RESULTS: A non-randomized prospective study of 24 participants with T2DM undergoing bariatric surgery. Measurements of fasting and 2-hour plasma glucose, insulin, C-peptide and measures of insulin sensitivity were recorded temporally during an oral glucose tolerance test pre-operatively and 6 months post-operatively. A responder was defined with a fasting glucose <5.6 mmol/L and HbA1c <6.0% postoperatively. Within the sample there were 11 responders and 13 non-responders at 6 months. There was a significant difference in the duration of diabetes between the groups. Fasting C-peptide (P≤0.05) and 2-hour C-peptide (P≤0.05) were higher in responders compared to non-responders. Significantly higher C-peptide levels were observed preoperatively at all time points for responders, with significantly higher area under the curve (AUC0-60 and AUC0-120). Using the lower quartiles for C-peptide levels, both fasting C-peptide (>2.5 ng/mL [0.83 nmol/L]) and 2-hour C-peptide (>5.2 ng/mL [1.73 nmol/L]) had a sensitivity and negative predictive value of 100% to predict T2DM remission. Logistic regression showed that C-peptide, duration of diabetes and BMI were associated with response. The area under the ROC curve was 0.94 and a regression model predicted diabetes remission with a sensitivity of 85.7% and a specificity of 88.9%. CONCLUSIONS: This study demonstrated that static (fasting) and dynamic (AUC, 2-hour) C-peptide measurements predict T2DM resolution 6 months following bariatric surgery. This work provides insight into C-peptide dynamics as a predictor of response to bariatric surgery.

Changes in plasma levels of N-arachidonoyl ethanolamine and N-palmitoylethanolamine following bariatric surgery in morbidly obese females with impaired glucose homeostasis.

AIM: We examined endocannabinoids (ECs) in relation to bariatric surgery and the association between plasma ECs and markers of insulin resistance. METHODS: A study of 20 participants undergoing bariatric surgery. Fasting and 2-hour plasma glucose, lipids, insulin, and C-peptide were recorded preoperatively and 6 months postoperatively with plasma ECs (AEA, 2-AG) and endocannabinoid-related lipids (PEA, OEA). RESULTS: Gender-specific analysis showed differences in AEA, OEA, and PEA preoperatively with reductions in AEA and PEA in females postoperatively. Preoperatively, AEA was correlated with 2-hour glucose (r = 0.55, P = 0.01), HOMA-IR (r = 0.61, P = 0.009), and HOMA %S (r = -0.71, P = 0.002). OEA was correlated with weight (r = 0.49, P = 0.03), waist circumference (r = 0.52, P = 0.02), fasting insulin (r = 0.49, P = 0.04), and HOMA-IR (r = 0.48, P = 0.05). PEA was correlated with fasting insulin (r = 0.49, P = 0.04). 2-AG had a negative correlation with fasting glucose (r = -0.59, P = 0.04). CONCLUSION: Gender differences exist in circulating ECs in obese subjects. Females show changes in AEA and PEA after bariatric surgery. Specific correlations exist between different ECs and markers of obesity and insulin and glucose homeostasis.

Changes in inflammatory markers after sleeve gastrectomy in patients with impaired glucose homeostasis and type 2 diabetes.

BACKGROUND: Bariatric surgery is an effective treatment for morbid obesity. Obesity and type 2 diabetes are associated with chronic inflammation. There is lack of data examining the effects of sleeve gastrectomy (SG) on inflammatory biomarkers. Our aim was to study the effects of SG on specific cytokines associated with obesity including interleukin-6 (IL-6), interleukin-10 (IL-10), leptin, adiponectin, and C-reactive protein (CRP) preoperatively, 1 and 6 months after surgery. METHODS: A nonrandomized prospective study comprising of 22 participants with impaired glucose homeostasis and type 2 diabetes undergoing SG (body mass index 50.1 kg/m(2), glycated hemoglobin [HbA1c] 53 mmol/mol). Serial measurements of IL-6, IL-10, leptin, adiponectin, and CRP were performed during oral glucose tolerance testing preoperatively, 1 and 6 months postoperatively. RESULTS: We observed significant improvements at 1 and 6 months in leptin (P≤.001) and CRP (P = .003) after SG. We also observed a significant reduction in IL-6 at 6 months (P = .001). No statistically significant differences were observed for adiponectin and IL-10. CONCLUSION: This study is the first to examine the detailed changes in the inflammatory cytokines after SG. Our study shows significant improvements in the inflammatory biomarkers after SG in patients with impaired glucose homeostasis and type 2 diabetes.

Temporal changes in glucose homeostasis and incretin hormone response at 1 and 6 months after laparoscopic sleeve gastrectomy.

BACKGROUND: Bariatric surgery is an effective treatment for morbid obesity. Current literature reports significant improvements in glucose homeostasis after malabsorptive surgery. There is limited evidence on the effects of laparoscopic sleeve gastrectomy (SG) on glucose-insulin homeostasis and postoperative incretin hormone response. The objective of this study was to examine the metabolic effects of SG on temporal changes in insulin and glucose homeostasis, incretin hormones and hepatic insulin clearance in patients with impaired glucose tolerance (IGT) and type 2 diabetes (T2 DM). METHODS: A nonrandomized prospective study comprising 22 participants undergoing SG (body mass index [BMI] 50.1 kg/m(2), glycated hemoglobin [HbA1c] 53 mmol/mol) and 15 participants undergoing biliopancreatic diversion (BPD) (BMI 62.1 kg/m(2), HbA1c 58 mmol/mol). Serial measurements of glucose, insulin, C-peptide, glucagon like peptide-1 (GLP-1) and glucose-dependent insulinotropic hormone (GIP) were performed during oral glucose tolerance testing preoperatively and 1 and 6 months postoperatively. Areas under the curve (AUC) were examined at 30, 60, and 120 minutes. RESULTS: Within the SG group, significant improvements were observed respectively at 1 and 6 months in glucose control (HbA1c: -0.9%, -1.3%), measures of insulin sensitivity (fasting insulin: -4.8 mU/L, -8.5 mU/L; fasting C-peptide: -0.6 pmol/L, -1.1 pmol/L; Homeostasis Model Assessment [HOMA-IR]: -0.144, -0.174; HOMA %S:+29.6,+92.4), hepatic insulin clearance (+0.07,+0.13) and postprandial GLP-1 response (AUC0-30 pmol h L(-1):+300,+331, AUC0-60:+300,+294, AUC0-120:+316,+295). These results were comparable to the BPD group. CONCLUSIONS: SG is associated with significant early improvements in insulin sensitivity and incretin hormone response and results in significant improvements in IGT/T2 DM.

Myxedema coma in a patient with subclinical hypothyroidism.

BACKGROUND: Myxedema coma is the extreme manifestation of hypothyroidism, typically seen in patients with severe biochemical hypothyroidism. Its occurrence in association with subclinical hypothyroidism is extremely unusual. We describe a patient with subclinical hypothyroidism who developed clinical manifestations of myxedema coma. SUMMARY: A 47-year-old woman presented to our endocrine clinic with complaints of fatigue and biochemical findings of subclinical hypothyroidism. She was started on treatment with thyroxine (T4) but remained unwell and was later admitted to hospital with hormone profile showing persisting subclinical hypothyroidism (elevated thyrotropin and normal free T4 [FT4] and free triiodothyronine [FT3]): FT4 10.7 pmol/L (reference range 10.3-24.5), FT3 2.7 pmol/L (reference range 2.67-7.03), and thyrotropin 6.09 mU/L (reference range 0.4-4.0). She subsequently developed hypothermia (temperature 33.2°C), circulatory collapse, and coma. Biochemical profile showed hyponatremia, elevated creatinine phosphokinase, metabolic acidosis, and renal failure. An echocardiogram revealed a moderate-sized pericardial effusion. We diagnosed myxedema coma and started treatment with intravenous T3. She responded dramatically with improvement in level of consciousness and normalization of metabolic parameters. We found no explanation other than hypothyroidism to account for the presentation. Adrenocorticotrophic hormone (ACTH) stimulation tests excluded adrenal insufficiency, and serum gonadotrophins were within the normal reference range. FT4 estimation by equilibrium dialysis excluded analytical interference, and molecular analysis for the thyroid hormone receptor ß gene associated with thyroid hormone resistance was negative. CONCLUSIONS: To the best of our knowledge this is the first report of myxedema coma in a patient with subclinical hypothyroidism. The reason for normal thyroid hormone levels is unclear but may reflect deviation from a higher pre-morbid set-point. The case highlights the importance of careful clinical evaluation in patients with disparate clinical and laboratory findings.

Value of baseline serum thyrotropin as a predictor of hypothyroidism in patients with diabetes mellitus.

OBJECTIVE: To determine whether serum thyrotropin measurement performed at diagnosis of diabetes mellitus or at initial patient contact predicts subsequent development of hypothyroidism. METHODS: We retrospectively reviewed the computerized records of patients attending annual visits between January 2008 and December 2008 at a hospital diabetes mellitus clinic. Serum free thyroxine and thyrotropin at current and baseline annual visits were documented. A Cox regression model was used to analyze the relationship between development of thyroid dysfunction and patient characteristics including age, sex, type of diabetes, and baseline serum thyrotropin concentration. Kaplan-Meier survival curves were generated for predictors of hypothyroidism. RESULTS: Clinical records of 1101 patients were reviewed (595 men [54%] and 506 women [46%]). Mean age was 60.0 ± 17 years. Two hundred twenty-three patients (20.3%) had type 1 DM and 878 (79.7%) had type 2 diabetes. Thyroid dysfunction was present in 136 patients (12.4%) at baseline and developed in 71 patients (6.4%) at follow-up (median duration, 37 months). Overt and subclinical hypothyroidism developed in 28 (2.5%) and 38 (3.5%) patients, respectively. Incident hypothyroidism was associated with baseline thyrotropin concentration greater than 2.2 mIU/L (relative risk, 10.4; confidence interval, 5.6-19.6; P<.001) and female sex (relative risk, 1.8; confidence interval, 1.1-2.9; P = .007). The predictive influence of sex was abolished in patients with a thyrotropin value greater than 2.2 mIU/L. This TSH threshold yielded an optimal sensitivity and specificity of 83% and 72%, respectively, for predicting hypothyroidism. CONCLUSIONS: Baseline serum thyrotropin predicted hypothyroidism in patients with diabetes mellitus even at thyrotropin concentrations within the reference range. Selective annual thyroid screening in diabetic patients with baseline thyrotropin concentrations greater than 2.2 mIU/L may be more cost-effective than universal screening.

Delayed diagnosis of hypopituitarism following severe traumatic brain injury.

The following case illustrates a 10-year delay in the diagnosis of hypopituitarism after severe traumatic brain injury in a 22-year-old man crushed by a forklift truck. His symptoms of mood changes, headaches and sleep pattern disturbances were attributed to post traumatic brain injury syndrome resulting in a delay in diagnosing the underlying pathology. Following recurrent episodes of symptomatic hyponatraemia, hypopituitarism was diagnosed. When pituitary hormone replacement treatment was given, there was clinical and biochemical improvement. There is currently very limited evidence in the literature to routinely screen patients post traumatic brain injury for pituitary dysfunction.

Injudicious antibiotic use leading to fulminating Clostridium difficile infection: a case report.

The case illustrates the myriad of fulminating complications due to Clostridium difficile infection in a previously healthy individual without any risk factors. Community acquired Clostridium difficile infection can occur even many weeks after the course of broad spectrum antibiotics. There is no definitive pattern or guidelines to predict who would develop the fulminating complications.