Genetic risk score based on obesity-related genes and progression in weight loss after bariatric surgery: a 60-month follow-up study.

BACKGROUND: Obesity is a polygenic multifactorial disease. Recent genome-wide association studies have identified several common loci associated with obesity-related phenotypes. Bariatric surgery (BS) is the most effective long-term treatment for patients with severe obesity. The huge variability in BS outcomes between patients suggests a moderating effect of several factors, including the genetic architecture of the patients. OBJECTIVE: To examine the role of a genetic risk score (GRS) based on 7 polymorphisms in 5 obesity-candidate genes (FTO, MC4R, SIRT1, LEP, and LEPR) on weight loss after BS. SETTING: University hospital in Spain. METHODS: We evaluated a cohort of 104 patients with severe obesity submitted to BS (Roux-en-Y gastric bypass or sleeve gastrectomy) followed up for >60 months (lost to follow-up, 19.23%). A GRS was calculated for each patient, considering the number of carried risk alleles for the analyzed genes. During the postoperative period, the percentage of excess weight loss total weight loss and changes in body mass index were evaluated. Generalized estimating equation models were used for the prospective analysis of the variation of these variables in relation to the GRS. RESULTS: The longitudinal model showed a significant effect of the GRS on the percentage of excess weight loss (P = 1.5 × 10-5), percentage of total weight loss (P = 3.1 × 10-8), and change in body mass index (P = 7.8 × 10-16) over time. Individuals with a low GRS seemed to experience better outcomes at 24 and 60 months after surgery than those with a higher GRS. CONCLUSION: The use of the GRS in considering the polygenic nature of obesity seems to be a useful tool to better understand the outcome of patients with obesity after BS.

Effect of semaglutide on weight loss and glycaemic control in patients with Prader-Willi Syndrome and type 2 diabetes.

Prader-Willi Syndrome (PWS) is the most common genetic cause of obesity, occurring in approximately 1 in 15,000 newborns. It results from the lack of expression of genes on the paternal allele of the chromosomal region 15q-11q13 (65-75% due to type 1 or type 2 deletion). Individuals with PWS experience associated symptoms such as hypotonia, hyperphagia, and early-onset obesity (before 5 years of age). Around 20% of adults with PWS also develop type 2 diabetes. Previous studies have shown the beneficial effects of GLP1-RA medications, such as exenatide and liraglutide, in treating type 2 diabetes in PWS. However, there is limited information available on the use of semaglutide in PWS. This study aimed to evaluate the effects of semaglutide on weight loss and glycaemic control in four patients with PWS and type 2 diabetes associated with obesity. The patients were started on weekly subcutaneous progressive doses of semaglutide.

Time in Range Analysis in Automated Insulin Delivery Era: Should Day and Nighttime Targets be the Same?

INTRODUCTION: Hybrid closed-loop systems (HCLS) use has shown that time in range (TIR) tends to improve more during the nighttime than during the day. This study aims to compare the conventional TIR, currently accepted as 70 to 180 mg/dL, with a proposed recalculated time in range (RTIR) considering a tighter glucose target of 70 to 140 mg/dL for the nighttime fasting period in T1DM patients under HCLS. METHODS: We conducted a retrospective study that included adults patients receiving treatment with Tandem t:slim X2 Control-IQ. Daytime TIR was characterized as glucose values between 70 and 180 mg/dL during the 07:01 to 23:59 time frame. Nighttime fasting TIR was specified as glucose values from 70 to 140 mg/dL between 00:00 and 07:00. The combination of the daytime and nighttime fasting glucose targets results in an RTIR, which was compared with the conventional TIR for each patient. The 14 days Dexcom G6 CGM data were downloaded from Tidepool platform and analyzed. RESULTS: We included 22 patients with a mean age of 49.7 years and diabetes duration of 24.7 years, who had been using automatic insulin delivery (AID) HCLS for a median of 305.3 days. We verified a mean conventional TIR of 68.7% vs a mean RTIR of 60.3%, with a mean percentage difference between these two metrics of -8.4%. A significant decrease in conventional TIR was verified when tighter glucose targets were considered during the nighttime period. No significant correlation was found between the percentage difference values and RTIR, even among the group of patients with the lowest conventional TIR. CONCLUSIONS: Currently, meeting the conventional TIR metrics may fall short of achieving an ideal level of glycemic control. An individualized strategy should be adopted until further data become available for a precise definition of optimal glucose targets.

Urinary loss of thyroid hormones: An issue to remember.

A 45-year-old woman suffering from primary hypothyroidism, previously well substituted with levothyroxine, was urgently referred from Primary Care to Endocrinology due to very elevated thyrotropin, free thyroxine at low limit of normality, very high cholesterol and generalised oedema. Hypothyroidism was suspected as the main aetiology of this clinical condition. A detailed examination showed nephrotic range proteinuria and the patient was finally diagnosed with lupus nephritis. Urinary loss of thyroid hormones, fundamentally linked to their transport proteins, in patients affected by nephrotic syndrome is sometimes a forgotten phenomenon and one which should be considered in patients with increased levothyroxine requirements. In this report, we present the details of this case and a brief review of the literature on this topic.

Genetic testing for familial hyperparathyroidism: clinical-genetic profile in a Mediterranean cohort.

Background: Approximately 10% of primary hyperparathyroidism cases are hereditary, due to germline mutations in certain genes. Although clinically relevant, a systematized genetic diagnosis is missing due to a lack of firm evidence regarding individuals to test and which genes to evaluate. Methods: A customized gene panel (AIP, AP2S1, CASR, CDC73, CDKN1A, CDKN1B, CDKN2B, CDKN2C, GCM2, GNA11, MEN1, PTH, RET, and TRPV6) was performed in 40 patients from the Mediterranean area with suspected familial hyperparathyroidism (≤45 years of age, family history, high-risk histology, associated tumour, multiglandular disease, or recurrent hyperparathyroidism). We aimed to determine the prevalence of germline variants in these patients, to clinically characterize the probands and their relatives, and to compare disease severity in carriers versus those with a negative genetic test. Results: Germline variants were observed in 9/40 patients (22.5%): 2 previously unknown pathogenic/likely pathogenic variants of CDKN1B (related to MEN4), 1 novel variant of uncertain significance of CDKN2C, 4 variants of CASR (3 pathogenic/likely pathogenic variants and 1 variant of uncertain significance), and 2 novel variants of uncertain significance of TRPV6. Familial segregation studies allowed diagnosis and early treatment of PHPT in first-degree relatives of probands. Conclusion: The observed prevalence of germline variants in the Mediterranean cohort under study was remarkable and slightly higher than that seen in other populations. Genetic screening for suspected familial hyperparathyroidism allows the early diagnosis and treatment of PHPT and other related comorbidities. We recommend genetic testing for patients with primary hyperparathyroidism who present with high-risk features.

Rapid Reduction of HbA1c and Early Worsening of Diabetic Retinopathy: A Real-world Population-Based Study in Subjects With Type 2 Diabetes.

OBJECTIVE: Early worsening of diabetic retinopathy (EWDR) due to the rapid decrease of blood glucose levels is a concern in diabetes treatment. The aim of the current study is to evaluate whether this is an important issue in subjects with type 2 diabetes with mild or moderate nonproliferative DR (NPDR), who represent the vast majority of subjects with DR attended in primary care. RESEARCH DESIGN AND METHODS: This is a retrospective nested case-control study of subjects with type 2 diabetes and previous mild or moderate NPDR. Using the SIDIAP ("Sistema d'informació pel Desenvolupament de la Recerca a Atenció Primària") database, we selected 1,150 individuals with EWDR and 1,150 matched control subjects (DR without EWDR). The main variable analyzed was the magnitude of the reduction of HbA1c in the previous 12 months. The reduction of HbA1c was categorized as rapid (>1.5% reduction in <12 months) or very rapid (>2% in <6 months). RESULTS: We did not find any significant difference in HbA1c reduction between case and control subjects (0.13 ± 1.21 vs. 0.21 ± 1.18; P = 0.12). HbA1c reduction did not show significant association with worsening of DR, neither in the unadjusted analyses nor in adjusted statistical models that included the main confounding variables: duration of diabetes, baseline HbA1c, presence of hypertension, and antidiabetic drugs. In addition, when stratification by baseline HbA1c was performed, we did not find that those patients with higher levels of HbA1c presented a higher risk to EWDR. CONCLUSIONS: Our results suggest that the rapid reduction of HbA1c is not associated with progression of mild or moderate NPDR.

Off-label use of an automated insulin delivery system in pregnant women with type 1 diabetes.

Using commercially available automated insulin delivery (AID) systems for treating type 1 diabetes during pregnancy remains controversial. This retrospective study assessed six pregnant women with type 1 diabetes who underwent AID therapy. Our observations revealed that AID treatment, in most cases, did not achieve the desired glycemic targets for pregnancy.

A Clinical-Genetic Score for Predicting Weight Loss after Bariatric Surgery: The OBEGEN Study.

Around 30% of the patients that undergo bariatric surgery (BS) do not reach an appropriate weight loss. The OBEGEN study aimed to assess the added value of genetic testing to clinical variables in predicting weight loss after BS. A multicenter, retrospective, longitudinal, and observational study including 416 patients who underwent BS was conducted (Clinical.Trials.gov- NCT02405949). 50 single nucleotide polymorphisms (SNPs) from 39 genes were examined. Receiver Operating Characteristic (ROC) curve analysis were used to calculate sensitivity and specificity. Satisfactory response to BS was defined as at nadir excess weight loss >50%. A good predictive model of response [area under ROC of 0.845 (95% CI 0.805-0.880), p < 0.001; sensitivity 90.1%, specificity 65.5%] was obtained by combining three clinical variables (age, type of surgery, presence diabetes) and nine SNPs located in ADIPOQ, MC4R, IL6, PPARG, INSIG2, CNR1, ELOVL6, PLIN1 and BDNF genes. This predictive model showed a significant higher area under ROC than the clinical score (p = 0.0186). The OBEGEN study shows the key role of combining clinical variables with genetic testing to increase the predictability of the weight loss response after BS. This finding will permit us to implement a personalized medicine which will be associated with a more cost-effective clinical practice.

Dynamic Insulin Basal Needs Estimation and Parameters Adjustment in Type 1 Diabetes.

Technology advances have made possible improvements such as Continuous Glucose Monitors, giving the patient a glucose reading every few minutes, or insulin pumps, allowing more personalized therapies. With the increasing number of available closed-loop systems, new challenges appear regarding algorithms and functionalities. Several of the analysed systems in this paper try to adapt to changes in some patients' conditions and, in several of these systems, other variables such as basal needs are considered fixed from day to day to simplify the control problem. Therefore, these systems require a correct adjustment of the basal needs profile which becomes crucial to obtain good results. In this paper a novel approach tries to dynamically determine the insulin basal needs of the patient and use this information within a closed-loop algorithm, allowing the system to dynamically adjust in situations of illness, exercise, high-fat-content meals or even partially blocked infusion sites and avoiding the need for setting a basal profile that approximately matches the basal needs of the patient. The insulin sensitivity factor and the glycemic target are also dynamically modified according to the situation of the patient. Basal insulin needs are dynamically determined through linear regression via the decomposition of previously dosed insulin and its effect on the patient's glycemia. Using the obtained value as basal insulin needs and other mechanisms such as basal needs modification through its trend, ISF and glycemic targets modification and low-glucose-suspend threshold, the safety of the algorithm is improved. The dynamic basal insulin needs determination was successfully included in a closed-loop control algorithm and was simulated on 30 virtual patients (10 adults, 10 adolescent and 10 children) using an open-source python implementation of the FDA-approved (Food and Drug Administration) UVa (University of Virginia)/Padova Simulator. Simulations showed that the proposed system dynamically determines the basal needs and can adapt to a partial blockage of the insulin infusion, obtaining similar results in terms of time in range to the case in which no blockage was simulated. The proposed algorithm can be incorporated to other current closed-loop control algorithms to directly estimate the patient's basal insulin needs or as a monitoring channel to detect situations in which basal needs may differ from the expected ones.

Growth Hormone (GH) Treatment Decreases Plasma Kisspeptin Levels in GH-Deficient Adults with Prader-Willi Syndrome.

Obesity and growth hormone (GH)-deficiency are consistent features of Prader-Willi syndrome (PWS). Centrally, kisspeptin is involved in regulating reproductive function and can stimulate hypothalamic hormones such as GH. Peripherally, kisspeptin signaling influences energy and metabolic status. We evaluated the effect of 12-month GH treatment on plasma kisspeptin levels in 27 GH-deficient adult PWS patients and analyzed its relationship with metabolic and anthropometric changes. Twenty-seven matched obese subjects and 22 healthy subjects were also studied. Before treatment, plasma kisspeptin concentrations in PWS and obese subjects were similar (140.20 (23.5-156.8) pg/mL vs. 141.96 (113.9-165.6) pg/mL, respectively, p = 0.979)) and higher (p = 0.019) than in healthy subjects (124.58 (107.3-139.0) pg/mL); plasma leptin concentrations were similar in PWS and obese subjects (48.15 (28.80-67.10) ng/mL vs. 33.10 (20.50-67.30) ng/mL, respectively, p = 0.152) and higher (p < 0.001) than in healthy subjects (14.80 (11.37-67.30) ng/mL). After GH therapy, lean body mass increased 2.1% (p = 0.03), total fat mass decreased 1.6% (p = 0.005), and plasma kisspeptin decreased to levels observed in normal-weight subjects (125.1(106.2-153.4) pg/mL, p = 0.027). BMI and leptin levels remained unchanged. In conclusion, 12-month GH therapy improved body composition and decreased plasma kisspeptin in GH deficient adults with PWS. All data are expressed in median (interquartile range).

Influence of the BDNF Val66Met polymorphism on weight loss after bariatric surgery: a 24-month follow-up.

BACKGROUND: Bariatric surgery is currently the most effective long-term treatment for severe obesity. However, interindividual variation in surgery outcome has been observed, and research suggests a moderating effect of several factors including baseline co-morbidities (e.g., type 2 diabetes [T2D] and genetic factors). No data are currently available on the interaction between T2D and variants in brain derived neurotrophic factor (BDNF) and its effect on weight loss after surgery. OBJECTIVES: To examine the role of the BDNF Val66Met polymorphism (rs6265) and the influence of T2D and their interaction on weight loss after bariatric surgery in a cohort of patients with severe obesity. SETTING: University hospital in Spain. METHODS: The present study evaluated a cohort of 158 patients with obesity submitted to bariatric surgery (Roux-en-Y gastric bypass or sleeve gastrectomy) followed up for 24 months (loss to follow-up: 0%). During the postoperative period, percentage of excess body mass index loss (%EBMIL), percentage of excess weight loss (%EWL), and total weight loss (%TWL) were evaluated. RESULTS: Longitudinal analyses showed a suggestive effect of BDNF genotype on the %EWL (P = .056) and indicated that individuals carrying the methionine (Met) allele may experience a better outcome after bariatric surgery than those with the valine/valine (Val/Val) genotype. We found a negative effect of a T2D diagnosis at baseline on %EBMIL (P = .004). Additionally, we found an interaction between BDNF genotype and T2D on %EWL and %EBMIL (P = .027 and P = .0004, respectively), whereby individuals with the Met allele without T2D displayed a greater %EWL and greater %EBMIL at 12 months and 24 months than their counterparts with T2D or patients with the Val/Val genotype with or without T2D. CONCLUSION: Our data showed an association between the Met variant and greater weight loss after bariatric surgery in patients without T2D. The presence of T2D seems to counteract this positive effect.

Managing gestational diabetes mellitus using a smartphone application with artificial intelligence (SineDie) during the COVID-19 pandemic: Much more than just telemedicine.

We describe our experience in the remote management of women with gestational diabetes mellitus during the COVID-19 pandemic. We used a mobile phone application with artificial intelligence that automatically classifies and analyses the data (ketonuria, diet transgressions, and blood glucose values), making adjustment recommendations regarding the diet or insulin treatment.

Role of the FKBP5 polymorphism rs1360780, age, sex, and type of surgery in weight loss after bariatric surgery: a follow-up study.

BACKGROUND: Emerging evidence suggests that the FK506 binding protein 51 (FKBP5/FKBP51), encoded by the FKBP5 gene, influences weight and metabolic regulation. The T allele of a functional polymorphism in FKBP5 (rs1360780), has been associated with the expression of FKBP51 and weight loss after bariatric surgery. OBJECTIVE: To examine the role of the FKBP5 rs1360780 polymorphism in relation to age, sex, and type of surgery in weight loss after bariatric surgery in patients with severe obesity. SETTING: University Hospital in Spain METHODS: A cohort of 151 obese patients submitted to Roux-en-Y gastric bypass (62.3%) and sleeve gastrectomy (37.7%) were followed-up during 24-months (t24m; loss to follow-up: 0%). During the postoperative period body mass index (BMI) and percentage of excess and total weight loss were evaluated. RESULTS: The BMI analysis showed an effect of the interaction FKBP5 genotype by sex (P = .0004) and a tendency to the interaction genotype by surgery (P = .048), so that men carrying the T allele had higher BMI at t24m than those without the T allele, and T-allele carriers that underwent sleeve gastrectomy had higher BMI at t24m than the noncarriers. Additionally, we found an interaction between FKBP5 and age for the percentage of excess weight loss and BMI (P = .0005 and P = 1.5e-7, respectively), whereby individuals >48 years with the T allele displayed significant differences for the analyzed variables at t24m compared with the homozygotes for the alternate C allele showing lower weight loss. CONCLUSION: FKBP5 rs1360780 genotype has specific effects on weight loss outcomes after bariatric surgery depending on sex, age, and type of surgery, suggesting worse results in older males carrying the T allele who have undergone sleeve gastrectomy.

Salivary Cortisol Determination in ACTH Stimulation Test to Diagnose Adrenal Insufficiency in Patients with Liver Cirrhosis.

PURPOSE: The prevalence of adrenal insufficiency (AI) in patients with decompensated liver cirrhosis is unknown. Because these patients have lower levels of cortisol-binding carrier proteins, their total serum cortisol (TSC) correlates poorly with free serum cortisol (FC). Salivary cortisol (SaC) correlates better with FC. We aimed to establish SaC thresholds for AI for the 250 µg intravenous ACTH test and to estimate the prevalence of AI in noncritically ill cirrhotic patients. METHODS: We included 39 patients with decompensated cirrhosis, 39 patients with known AI, and 45 healthy volunteers. After subjects fasted ≥8 hours, serum and saliva samples were collected for determinations of TSC and SaC at baseline 0'(T0) and at 30-minute intervals after intravenous administration of 250 µg ACTH [30'(T30), 60'(T60), and 90'(T90)]. RESULTS: Based on the findings in healthy subjects and patients with known AI, we defined AI in cirrhotic patients as SaC-T0< 0.08 µg/dL (2.2 nmol/L), SaC-T60 < 1.43 µg/dl (39.5 nmol/L), or ΔSaC<1 µg/dl (27.6 nmol/L). We compared AI determination in cirrhotic patients with the ACTH test using these SaC thresholds versus established TSC thresholds (TSC-T0< 9 µg/dl [248 nmol/L], TSC-T60 < 18 µg/dl [497 nmol/L], or ΔTSC<9 µg/dl [248 nmol/L]). SaC correlated well with TSC. The prevalence of AI in cirrhotic patients was higher when determined by TSC (48.7%) than by SaC (30.8%); however, this difference did not reach statistical significance. AI was associated with sex, cirrhosis etiology, and Child-Pugh classification. CONCLUSIONS: Measuring SaC was more accurate than TSC in the ACTH stimulation test. Measuring TSC overestimated the prevalence of AI in noncritically ill cirrhotic patients.

Simultaneous onset of type 1 diabetes mellitus and silent thyroiditis under durvalumab treatment

Summary: Durvalumab, a human immunoglobulin G1 kappa monoclonal antibody that blocks the interaction of programmed cell death ligand 1 (PD-L1) with the PD-1 and CD80 (B7.1) molecules, is increasingly used in advanced neoplasias. Durvalumab use is associated with increased immune-related adverse events. We report a case of a 55-year-old man who presented to our emergency room with hyperglycaemia after receiving durvalumab for urothelial high-grade non-muscle-invasive bladder cancer. On presentation, he had polyuria, polyphagia, nausea and vomiting, and laboratory test revealed diabetic ketoacidosis (DKA). Other than durvalumab, no precipitating factors were identified. Pre-durvalumab blood glucose was normal. The patient responded to treatment with intravenous fluids, insulin and electrolyte replacement. Simultaneously, he presented a thyroid hormone pattern that evolved in 10 weeks from subclinical hyperthyroidism (initially attributed to iodinated contrast used in a previous computerised tomography) to overt hyperthyroidism and then to severe primary hypothyroidism (TSH: 34.40 µU/mL, free thyroxine (FT4): <0.23 ng/dL and free tri-iodothyronine (FT3): 0.57 pg/mL). Replacement therapy with levothyroxine was initiated. Finally, he was tested positive for anti-glutamic acid decarboxylase (GAD65), anti-thyroglobulin (Tg) and antithyroid peroxidase (TPO) antibodies (Abs) and diagnosed with type 1 diabetes mellitus (DM) and silent thyroiditis caused by durvalumab. When durvalumab was stopped, he maintained the treatment of multiple daily insulin doses and levothyroxine. Clinicians need to be alerted about the development of endocrinopathies, such as DM, DKA and primary hypothyroidism in the patients receiving durvalumab. Learning Points: Patients treated with anti-PD-L1 should be screened for the most common immune-related adverse events (irAEs). Glucose levels and thyroid function should be monitored before and during the treatment. Durvalumab is mainly associated with thyroid and endocrine pancreas dysfunction. In the patients with significant autoimmune background, risk­benefit balance of antineoplastic immunotherapy should be accurately assessed.

Decision Support in Diabetes Care: The Challenge of Supporting Patients in Their Daily Living Using a Mobile Glucose Predictor.

BACKGROUND: In type 1 diabetes mellitus (T1DM), patients play an active role in their own care and need to have the knowledge to adapt decisions to their daily living conditions. Artificial intelligence applications can help people with type 1 diabetes in decision making and allow them to react at time scales shorter than the scheduled face-to-face visits. This work presents a decision support system (DSS), based on glucose prediction, to assist patients in a mobile environment. METHODS: The system's impact on therapeutic corrective actions has been evaluated in a randomized crossover pilot study focused on interprandial periods. Twelve people with type 1 diabetes treated with insulin pump participated in two phases: In the experimental phase (EP) patients used the DSS to modify initial corrective decisions in presence of hypoglycemia or hyperglycemia events. In the control phase (CP) patients were asked to follow decisions without knowing the glucose prediction. A telemedicine platform allowed participants to register monitoring data and decisions and allowed endocrinologists to supervise data at the hospital. The study period was defined as a postprediction (PP) time window. RESULTS: After knowing the glucose prediction, participants modified the initial decision in 20% of the situations. No statistically significant differences were found in the PP Kovatchev's risk index change (-1.23 ± 11.85 in EP vs -0.56 ± 6.06 in CP). Participants had a positive opinion about the DSS with an average score higher than 7 in a usability questionnaire. CONCLUSION: The DSS had a relevant impact in the participants' decision making while dealing with T1DM and showed a high confidence of patients in the use of glucose prediction.

Documento de consenso SED-SEEP sobre el uso de la monitorización continua de la glucosa en España / SED-SEEP Consensus document on the use of continuous glucose monitoring in Spain

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Human Subcutaneous Tissue Response to Glucose Sensors: Macrophages Accumulation Impact on Sensor Accuracy.

BACKGROUND: Subcutaneous (s.c.) glucose sensors have become a key component in type 1 diabetes management. However, their usability is limited by the impact of foreign body response (FBR) on their duration, reliability, and accuracy. Our study gives the first description of human acute and subacute s.c. response to glucose sensors, showing the changes observed in the sensor surface, the inflammatory cells involved in the FBR and their relationship with sensor performance. METHODS: Twelve obese patients (seven type 2 diabetes) underwent two abdominal biopsies comprising the surrounding area where they had worn two glucose sensors: the first one inserted 7 days before and the second one 24 h before biopsy procedure. Samples were processed and studied to describe tissue changes by two independent pathologists (blind regarding sensor duration). Macrophages quantification was studied by immunohistochemistry methods in the area surrounding the sensor (CD68, CD163). Sensor surface changes were studied by scanning electron microscopy. Seven-day continuous glucose monitoring records were considered inaccurate when mean absolute relative difference was higher than 10%. RESULTS: Pathologists were able to correctly classify all the biopsies regarding sensor duration. Acute response (24 h) was characterized by the presence of neutrophils while macrophages were the main cell involved in subacute inflammation. The number of macrophages around the insertion hole was higher for less accurate sensors compared with those performing more accurately (32.6 ± 14 vs. 10.6 ± 1 cells/0.01 mm2; P < 0.05). CONCLUSION: The accumulation of macrophages at the sensor-tissue interface is related with decrease in accuracy of the glucose measure.