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.

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.

Measurement of Serum N-Glycans in the Assessment of Early Vascular Aging (Arterial Stiffness) in Adults With Type 1 Diabetes.

OBJECTIVE: Vascular aging (arterial stiffness [AS]) is an inflammation-linked process that predicts macro- and microvascular complications in adults with type 1 diabetes (T1D). We evaluated the utility of measuring the inflammation-linked N-glycans GlycA and GlycB to assess vascular aging in adults with T1D. RESEARCH DESIGN AND METHODS: Eighty-four adults with T1D (>10-year duration without cardiovascular events) and 68 healthy control subjects were evaluated for clinical characteristics (including microvascular complications in patients with T1D), aortic pulse wave velocity (aPWV) (surrogate measure of AS), and serum GlycA and GlycB (peak area [concentration] and height/width [H/W] ratio) using 1H-nuclear magnetic resonance spectroscopy. RESULTS: Patients with T1D had higher median (interquartile range) values than healthy control subjects for (P < 0.001 for all comparisons) aPWV 7.9 (6.9-9.1) vs. 6.1 (5.5-6.7) m/s, GlycA 850.4 (781.3-916.1) vs. 652.4 (581.5-727.1) µmoL; GlycB 386.1 (353.2-426.3) vs. 310.0 (280.5-331.9) µmol/L), H/W ratio of GlycA 16.5 (14.9-18.1) vs. 15.0 (13.7-16.7), and H/W ratio of GlycB 5.0 (4.6-5.5) vs. 4.0 (3.4-4.3). Moreover, aPWV correlated (P < 0.001 for all correlations) with GlycA (r = 0.550) and GlycB (r = 0.423) concentrations and with H/W ratios of GlycA (r = 0.453) and GlycB (r = 0.510). Adjusting for potential confounders, GlycA concentration (ß = 0.212, P < 0.001) and the H/W ratios of GlycA (ß = 0.150, P = 0.009) and GlycB (ß = 0.155, P = 0.011) remained independently associated with aPWV. C-statistics for detecting individuals with aPWV >10 m/s were 0.866 (95% CI 0.794-0.937) for GlycA levels and 0.862 (0.780-0.943) for H/W ratio of GlycB. CONCLUSIONS: Measurement of serum GlycA and GlycB may have utility in assessing vascular aging in adults with T1D of >10-year duration and no previous cardiovascular events.

Arterial Stiffness in Type 1 Diabetes: The Case for the Arterial Wall Itself as a Target Organ.

Arterial stiffness (AS) integrates the cumulative burden of known and unknown cardiovascular risk factors on the elastic wall of large arteries along the lifespan of an individual. As a marker of vascular aging, AS is an independent predictor of cardiovascular events and improves cardiovascular risk prediction when added to the Framingham Risk Score. In addition, AS may affect the microvasculature and promote the development of microvascular complications. Its impact on both the macro- and microvasculature has led to the concept that the arterial wall itself should be considered as a target organ. Here, we review the biological and clinical consequences of AS on the macro- and microvasculature and the measurement of AS in routine clinical practice. We also discuss the pathophysiological mechanisms underpinning AS development using diabetes and, in particular, type 1 diabetes, as a disease model with a high risk of cardiovascular events and microvascular complications that are accelerated by AS.

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.

Utility of Insulin Resistance in Estimating Cardiovascular Risk in Subjects with Type 1 Diabetes According to the Scores of the Steno Type 1 Risk Engine.

BACKGROUND: We sought to assess the potential of insulin resistance (IR) for estimating cardiovascular disease (CVD) risk in adults with type 1 diabetes (T1DM) according to the scores of the Steno Type 1 Risk Engine (ST1RE). METHODS: A total of 179 adults with T1DM (50.8% men, age 41.2 ± 13.1 years, duration of T1DM 16 (12-23) years) without established CVD were evaluated. IR was assessed by the estimation of insulin sensitivity (eIS) using two validated prediction equations: the estimated insulin sensitivity developed from the Pittsburgh Epidemiology of Diabetes Complications Study (eIS-EDC) and the estimated insulin sensitivity developed from Coronary Artery Calcification in T1DM Study (eIS-CACTI) ST1RE was used to estimate 10-year CVD risk and to classify subjects into three groups according to their risk: low (<10%; n = 105), moderate (10-20%; n = 53), and high (≥20%; n = 21). RESULTS: Both eIS-EDC and eIS-CACTI correlated negatively with ST1RE scores (eIS-EDC: r = -0.636, p < 0.001; eIS-CACTI: r = -0.291, p < 0.001). The C-statistic for predicting moderate/high risk and high risk was 0.816 (95% confidence interval (CI): 0.754-0.878) and 0.843 (95% CI: 0.772-0.913), respectively, for the eIS-EDC equation, and was 0.686 (95% CI: 0.609-0.763) and 0.646 (95% CI: 0.513-0.778), respectively, for the eIS-CACTI equation. The eIS-EDC equation had a significantly higher C-statistic both for moderate-/high-risk (p = 0.001) and high-risk (p = 0.007) subjects. Two cut-off points of eIS-EDC were identified for detecting moderate/high risk (8.52 mg·kg-1·min-1; sensitivity 74% and specificity 76%) and high risk (8.08 mg·kg-1·min-1; sensitivity 65% and specificity 95%) with potential applicability in clinical practice. CONCLUSIONS: eIS negatively correlates with the score of CVD risk in the ST1RE. Two cut-off points of eIS are reported with potential utility in clinical practice for detecting adults with T1DM with the highest CVD risk.

Specific Nuclear Magnetic Resonance Lipoprotein Subclass Profiles and Central Arterial Stiffness in Type 1 Diabetes Mellitus: A Case Control Study.

BACKGROUND: Dyslipidemia has been associated with vascular complications of type 1 diabetes mellitus (T1DM). We examined the proton nuclear magnetic resonance (NMR)-assessed lipoprotein subclass profiles in subjects with T1DM compared with those of healthy subjects and assessed the potential relationship of these profiles with arterial stiffness. METHODS: Eighty-four participants with T1DM of at least 10 years duration and no clinical cardiovascular disease (age: 35-65 years; 50% men) and 42 healthy participants were evaluated for: (1) clinical and anthropometric data (including classical cardiovascular risk factors), (2) insulin sensitivity by estimated glucose disposal rate, (3) microvascular complications, (4) NMR-assessed lipoprotein subclass profile, and (5) arterial stiffness (aortic pulse wave velocity). RESULTS: Participants with T1DM had an apparently better conventional lipid profile than healthy participants, but with significant differences in NMR-assessed lipoprotein profiles such as higher triglyceride content of low-density lipoprotein (LDL) and high-density lipoprotein (HDL). In healthy participants, arterial stiffness was associated with NMR-based LDL subclasses. By contrast, in T1DM participants, arterial stiffness was independently associated mainly with NMR-based very-low-density lipoprotein (VLDL) subclasses: positively with total VLDL particles (and subclasses) and VLDL triglyceride content, and negatively with LDL and HDL particle sizes. These results were maintained after adjustments for classical cardiovascular risk factors. CONCLUSIONS: Subjects with T1DM, while having an apparently better conventional lipid profile than healthy controls, presented significant alterations in their NMR-assessed lipoprotein profile. The association between arterial stiffness and NMR-assessed lipoprotein profiles also differed in both groups. These results support a potential role of the identified differences in the residual cardiovascular risk in T1DM.

Arterial stiffness is highly correlated with the scores obtained from the Steno Type 1 Risk Engine in subjects with T1DM.

OBJECTIVES: Currently used risk scores for type 2 diabetes mellitus (T2DM) clearly underestimate cardiovascular risk in type 1 diabetes (T1DM). Hence, there is a need to develop novel and specific risk-estimation tools for this population. We aimed to assess the relationship between the Steno Type 1 Risk Engine (ST1RE) and arterial stiffness (AS), and to identify potential cut-off points of interest in clinical practice. DESIGN AND METHODS: A total of 179 patients with T1DM (50.8% men, mean age 41.2±13.1 years), without established cardiovascular disease, were evaluated for clinical and anthropometric data (including classical cardiovascular risk factors), and AS measured by aortic pulse-wave velocity (aPWV). The ST1RE was used to estimate 10-year cardiovascular risk and patients were classified into 3 groups: low- (<10%; n = 105), moderate- (10-20%; n = 53) and high-risk (≥20%; n = 21). RESULTS: When compared with the low- and moderate-risk groups, patients in the high-risk group were older, had higher prevalence of hypertension, dyslipidemia and insulin-resistance, and had higher body-mass index and HbA1c. aPWV increased in parallel with estimated cardiovascular risk (6.4±1.0, 8.4±1.3 and 10.3±2.6m/s; p<0.001). As an evaluation of model performance, the C-statistic of aPWV was 0.914 (95% confidence interval [CI]:0.873-0.950) for predicting moderate/high-risk and 0.879 (95%CI:0.809-0.948) for high-risk, according to the ST1RE. The best cut-off points of aPWV were 7.3m/s (sensitivity:86%, specificity:83%) and 8.7m/s (sensitivity:76%, specificity:86%) for moderate/high- and high-risk, respectively. CONCLUSIONS: AS is highly correlated with the scores obtained from the ST1RE. We have identified two cut-off points of AS that can clearly discriminate moderate/high- and high-risk T1DM patients, which could be of great value in clinical practice.

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.

Takotsubo cardiomyopathy in amiodarone-induced hyperthyroidism.

SUMMARY: Takotsubo cardiomyopathy (TC) is an atypical, severe but reversible form of acute heart insufficiency. It typically presents with left ventricular failure, transient apical and mid-segments hypokinesis, absence of significant coronary stenosis and new electrographic abnormalities and/or elevation in serum cardiac enzymes. Although TC ('broken heart syndrome') has classically been associated with emotional trauma, evidence suggests that other precipitants might exist, including iatrogenic and thyroid-mediated forms. Thyroid disease is a relatively common comorbidity in TC patients. We report a case of TC in a postmenopausal female with no history of emotional trauma or other potential precipitant factors who was diagnosed with amiodarone-induced hyperthyroidism during her hospital stay. Though some case reports of thyroid-related TC exist, we are not aware of any other reported case of TC precipitated by amiodarone-induced hyperthyroidism. LEARNING POINTS: TC is a relatively new, rare, transient, severe, but reversible cardiovascular condition that is characterized by an acute left ventricular cardiac failure, which can clinically, analytically and electrocardiographically mimic an acute myocardial infarction.Many precipitant factors have been described in TC, being the most classical and emotional trauma. However, thyroid dysfunction is also a significant condition frequently found in patients with TC.A hypercatecholaminergic state leading to cardiomyocyte damage has been established as the main fact of TC physiopathology. Hyperthyroidism induces an upregulation of ß-adrenergic receptors.Both hyperthyroidism and hypothyroidism have been related with TC development. Most reported cases of TC involving thyroid dysfunction correspond to hyperthyroidism due to Graves-Basedow disease, but there are also descriptions with severe hypothyroidism, radioiodine treatment or thyroid surgery.Amiodarone is a class III antiarrhythmic agent widely used, and it is a well-known cause of thyroid dysfunction, which can present either with hypothyroidism or hyperthyroidism, as approximately 40 percent of the amiodarone molecule is composed of iodine.In this case, a type II amiodarone-induced hyperthyroidism was the precipitant factor of a TC in a patient with a pre-existing atrial fibrillation. Given the high prevalence of atrial fibrillation and the wide use of amiodarone, the risk of this iatrogenic effect should be taken into account.

Type 1 diabetes: Developing the first risk-estimation model for predicting silent myocardial ischemia. The potential role of insulin resistance.

OBJECTIVES: The aim of the study was to develop a novel risk estimation model for predicting silent myocardial ischemia (SMI) in patients with type 1 diabetes (T1DM) and no clinical cardiovascular disease, evaluating the potential role of insulin resistance in such a model. Additionally, the accuracy of this model was compared with currently available models for predicting clinical coronary artery disease (CAD) in general and diabetic populations. RESEARCH, DESIGN AND METHODS: Patients with T1DM (35-65years, >10-year duration) and no clinical cardiovascular disease were consecutively evaluated for: 1) clinical and anthropometric data (including classical cardiovascular risk factors), 2) insulin sensitivity (estimate of glucose disposal rate (eGDR)), and 3) SMI diagnosed by stress myocardial perfusion gated SPECTs. RESULTS: Eighty-four T1DM patients were evaluated [50.1±9.3 years, 50% men, 36.9% active smokers, T1DM duration: 19.0(15.9-27.5) years and eGDR 7.8(5.5-9.4)mg·kg-1·min-1]. Of these, ten were diagnosed with SMI (11.9%). Multivariate logistic regression models showed that only eGDR (OR = -0.593, p = 0.005) and active smoking (OR = 7.964, p = 0.018) were independently associated with SMI. The AUC of the ROC curve of this risk estimation model for predicting SMI was 0.833 (95%CI:0.692-0.974), higher than those obtained with the use of currently available models for predicting clinical CAD (Framingham Risk Equation: 0.833 vs. 0.688, p = 0.122; UKPDS Risk Engine (0.833 vs. 0.559; p = 0.001) and EDC equation: 0.833 vs. 0.558, p = 0.027). CONCLUSION: This study provides the first ever reported risk-estimation model for predicting SMI in T1DM. The model only includes insulin resistance and active smoking as main predictors of SMI.

Naltrexone sustained-release/bupropion sustained-release for the management of obesity: review of the data to date.

Obesity is an emerging disease worldwide. Changes in living habits, especially with increased consumption of high-calorie foods and decreased levels of physical activity, lead to an energy imbalance that brings weight gain. Overweight and obesity are major risk factors for several chronic diseases (including cardiovascular diseases, diabetes, and cancer), reduce quality of life, and are associated with higher mortality. For all these reasons, it is of the utmost importance that the trend be reversed and obese people enabled to lose weight. It is known that eating a healthy diet and exercising regularly can help prevent obesity, but data show that in many cases these steps are not enough. This is the reason why, over the last few decades, several antiobesity drugs have been developed. However, the disappointing results demonstrated for the vast majority of them have not discouraged the pharmaceutical industry from continuing to look for an effective drug or combination of drugs. The systematic review presented here focuses on naltrexone sustained-release/bupropion sustained-release combination (Contrave(®)). We conclude from the current published reports that its effectiveness in the treatment of obesity can be estimated as a placebo-subtracted weight loss of around 4.5%. This weight reduction is moderate but similar to other antiobesity drugs. The safety profile of this combination is acceptable, despite additional data regarding cardiovascular disease being needed.