Clusters of adipose tissue dysfunction in adults with type 2 diabetes identify those with worse lipidomic profile despite similar glycaemic control.

AIMS: To investigate clusters of adipose tissue dysfunction, that is, with adipose tissue insulin resistance (ADIPO-IR) and large waist circumference (WC), identify a worse lipidomic profile characterised by a high proportion of lipids rich in saturated fatty acids (SFA). MATERIALS AND METHODS: Hierarchical clustering based on WC and ADIPO-IR (calculated as fasting plasma non-esterified fatty acids times fasting plasma insulin, FFA×INS), was performed in 192 adults with overweight/obesity and type 2 diabetes (T2D) treated with metformin (HbA1c = 7.8%). Free fatty acid composition and lipidomic profile were measured by mass spectrometry (GC-MS and LC-MSQTOF). Indexes of fatty acid desaturation (stearoyl-coA desaturase-1 activity, SCD116 = palmitoleic acid/palmitic acid and SCD118 = oleic acid/stearic acid) and of insulin resistance (HOMA-IR) were also calculated. RESULTS: Three clusters were identified: CL1 (ADIPO-IR = 4.9 ± 2.4 and WC = 96±7 cm, mean ± SD), CL2 (ADIPO-IR = 6.5 ± 2.5 and WC = 114 ± 7 cm), and CL3 (ADIPO-IR = 15.0 ± 4.7 and WC = 107 ± 8 cm). Insulin concentrations, ADIPO-IR, and HOMA-IR significantly increased from CL1 to CL3 (all p < 0.001), while fasting glucose concentrations, HbA1c, dietary lipids and caloric intake were similar. Moreover, CL3 showed significantly higher concentrations of monounsaturated free fatty acids, oleic and palmitoleic acids, triglycerides (TAG) rich in saturated FA and associated with de novo lipogenesis (i.e., TAG 46-50), higher SCD116, SCD118, ceramide (d18:0/18:0), and phosphatidylcholine aa(36:5) compared with CL1/CL2 (all p < 0.005). CONCLUSIONS: High ADIPO-IR and large WC identify a worse lipid profile in T2D characterised by complex lipids rich in SFA, likely due to de novo synthesis given higher plasma monounsaturated FFA and increased desaturase activity indexes. REGISTRATION NUMBER TRIAL: ID NCT00700856 https://clinicaltrials.gov.

Eating habits and sleep quality in individuals with type 1 diabetes on continuous glucose monitoring and insulin pump.

BACKGROUND AND AIMS: Sleep disorders are bidirectionally linked with eating behaviors and glucose metabolism, which could be clinically relevant in type 1 diabetes (T1D). We investigated the relationship between dietary habits and sleep quality in individuals with T1D on insulin pumps and continuous glucose monitoring (CGM). METHODS AND RESULTS: In a cross-sectional study, dietary habits (7-day food diary, EPIC questionnaire) and sleep quality (Pittsburgh Sleep Quality Index questionnaire) were assessed in 59 men and 58 women with T1D, aged 19-79 years, using CGM and insulin pump. Differences in dietary habits and blood glucose after dinner (6 h) between participants differing in sleep quality, sleep duration, and sleep onset latency were evaluated. Bad Sleepers (n = 81) were twice as prevalent as Good Sleepers (n = 36) and had a significantly higher intake of fat than Good Sleepers (dinner: 30.7 ± 10.7 vs. 24.0 ± 10.5 g, p = 0.004). Short sleepers had a significantly higher usual intake (g/1000 kcal) of coffee and tea (90.4 ± 71.7 vs. 62.0 ± 35.6), alcoholic (47.8 ± 51.1 vs. 28.9 ± 31.5) and carbonated beverages (21.8 ± 38.1 vs. 9.3 ± 17.2) (p < 0.05 for all) than Long Sleepers. Long Sleep Onset Latency was associated with a significantly higher fat intake at dinner (41.8 ± 7.4 vs. 38.1 ± 9.1 % total energy, p = 0.029) than Short Sleep Onset Latency. No significant differences in post-dinner blood glucose levels were detected between participants with good or bad sleep quality. CONCLUSION: Sleep disruption is common in T1D and is associated with unhealthy dietary choices, especially at dinner, independently of post-dinner blood glucose control.

Dietary treatment of type 1 diabetes: Beyond carbohydrate counting to fight cardiovascular risk.

AIMS: Type 1 diabetes (T1D) is tied to an increased risk of cardiovascular morbidity and mortality. Dietary treatment would be an elective therapeutic strategy to fight this risk. However, it is not known what the best dietary approach is. We revisited the currently available literature on the nutritional treatment of T1D in the light of their potential comprehensive effects on the management of cardio-metabolic risk factors (body weight, fasting and postprandial glucose and lipid metabolism). DATA SYNTHESIS: Nutritional research in T1D is mainly focused on blood glucose control, with most of the trials aiming at evaluating the acute effects of nutrients on postprandial glycemic response. The effects of the quantity and quality of nutrients and some specific foods on other metabolic risk factors have been explored mainly in cross-sectional analysis. Very few well-designed nutritional trials evaluated the best dietary approach to comprehensively manage cardiovascular risk by targeting along with blood glucose control, overweight, fasting and postprandial dyslipidemia. Therefore, the current best practice guidance for the dietary management of cardiovascular risk in T1D is generally based on evidence from patients with type 2 diabetes. CONCLUSIONS: Well-conducted nutritional trials specifically designed for T1D are needed to identify the best dietary treatment to fight cardiovascular risk in these patients.

Evaluation of eating habits by 7-day food record: web-PC vs. traditional paper format.

The aim of this study was to evaluate the validity of a web-based 7-day food-record using METADIETA-web link (Meteda s.r.l.) - a professional software used in nutritional practice and research - compared with the traditional paper format. Twenty-six healthy adults of both sexes were recruited in this cross-over study based on the number coming from the sample size calculation, and randomly assigned to start with METADIETA-web or traditional 7-Day Food-Diary. All the 7-day food-diaries were recorded in the Metadieta-software. The System Usability Scale (SUS) questionnaire was administered to evaluate the participants' preferences in terms of usability, acceptability, and feasibility. Differences in energy intake, nutrient composition, and SUS between the digital and traditional modalities were evaluated. Energy and nutrients were not significantly different between the two methods with a variation <15%, with alcohol intake showing the strongest relation (0.1% variation). The Interclass Correlation Coefficient showed a grade of consistency between the two methods excellent for alcohol, good for proteins, carbohydrates, and fibre, moderate for energy and saturated fat, and poor for total fat and cholesterol. SUS suggested that the web-based platform was in general well accepted, but highlighted some inconsistencies and complexity compared to the written food diary. The web-based 7-day food-record may allow an accurate and quicker analysis of food timing than conventional approaches, seeming reliable for energy and macronutrient composition, making it a potentially attractive tool for nutritional research. However, the reported inconsistencies and complexity must be considered and addressed.

Dietary determinants of postprandial blood glucose control in adults with type 1 diabetes on a hybrid closed-loop system.

AIMS/HYPOTHESIS: The aim of this work was to assess the relationship between meal nutrients and postprandial blood glucose response (PGR) in individuals with type 1 diabetes on a hybrid closed-loop system (HCLS). METHODS: The dietary composition of 1264 meals (398 breakfasts, 441 lunches and 425 dinners) was assessed by 7-day food records completed by 25 individuals with type 1 diabetes on HCLSs (12 men/13 women, mean ± SD age 40 ± 12 years, mean ± SD HbA1c 51 ± 10 mmol/mol [6.9 ± 0.2%]). For each meal, PGR (continuous glucose monitoring metrics, glucose incremental AUCs) and insulin doses (pre-meal boluses, post-meal microboluses automatically delivered by the pump and adjustment boluses) over 6 h were evaluated. RESULTS: Breakfast, lunch and dinner significantly differed with respect to energy and nutrient intake and insulin doses. The blood glucose postprandial profile showed an earlier peak after breakfast and a slow increase until 4 h after lunch and dinner (p < 0.001). Mean ± SD postprandial time in range (TIR) was better at breakfast (79.3 ± 22.2%) than at lunch (71.3 ± 23.9%) or dinner (70.0 ± 25.9%) (p < 0.001). Significant negative predictors of TIR at breakfast were total energy intake, per cent intake of total protein and monounsaturated fatty acids, glycaemic load and absolute amounts of cholesterol, carbohydrates and simple sugars consumed (p < 0.05 for all). No significant predictors were detected for TIR at lunch. For TIR at dinner, a significant positive predictor was the per cent intake of plant proteins, while negative predictors were glycaemic load and intake amounts of simple sugars and carbohydrate (p < 0.05 for all). CONCLUSIONS/INTERPRETATION: This study shows that nutritional factors other than the amount of carbohydrate significantly influence postprandial blood glucose control. These nutritional determinants vary between breakfast, lunch and dinner, with differing effects on postprandial blood glucose profile and insulin requirements, thus remaining a challenge to HCLSs.

Dietary influence on adiponectin in patients with type 2 diabetes.

BACKGROUND: Here, we evaluate the effects of a diet rich in low-glycaemic index carbohydrates and fibre (CHO/Fibre diet) or monounsaturated fatty acids (MUFA diet), on fasting and postprandial adiponectin concentrations and their relationship with the beneficial effects of the experimental diets on postprandial glucose metabolism and liver fat in type 2 diabetes (T2D). METHODS: Fasting and postprandial adiponectin plasma concentrations were measured before and after dietary interventions in the participants to a randomized controlled trial (NCT01025856), wherein 37 men and 8 women with T2D, aged 35-70 years, followed a CHO/Fibre diet or a MUFA diet for an 8-week period. Hepatic fat content by 1 H NMR and fasting and postprandial plasma glucose and insulin measurements were also available. RESULTS: Fasting adiponectin plasma levels did not change after both diets. Postprandial adiponectin significantly increased after the CHO/fibre diet (9.9 ± 1.6 µg/mL vs. 10.8 ± 2.3 µg/mL; P = .033) but not after the MUFA diet (10.6 ± 1.8 µg/mL vs. 10.6 ± 1.6 µg/mL; P = .935) with a significant difference between changes (P = .035). In the combined CHO/Fibre and MUFA groups, fasting and postprandial adiponectin significantly and inversely correlated with postprandial insulin iAUC at baseline and after intervention, and with liver fat content after intervention. CONCLUSIONS: A diet rich in CHO/Fibre increased postprandial plasma adiponectin significantly more than a MUFA diet in patients with T2D. Independently of diet, adiponectin levels associated with postprandial insulin concentrations. The dietary interventions modulated the relationship between adiponectin and liver fat.

An Oily Fish Diet Improves Subclinical Inflammation in People at High Cardiovascular Risk: A Randomized Controlled Study.

Interest has arisen on the anti-inflammatory action of dietary components, including long-chain n-3 fatty acids (LCn3) and polyphenols (PP). The aim of this study was to evaluate the effects of diets rich in PP and oily fish (high-LCn3 diets) on markers of subclinical inflammation and growth factors in people at high cardiometabolic risk. Individuals with high waist circumference and one more component of metabolic syndrome were randomized to one of the following isoenergetic diets: low LCn3&PP, high LCn3, high PP, high LCn3&PP. Before and after 8 weeks, fasting and postprandial plasma concentrations of hs-CRP and fasting serum concentrations of IL-1, IL-4, IL-6, IL-10, IL-17, INF-, TNF-, FGF, VEGF, PDGF-, G-CSF, and GM-CSF were determined. An oily fish diet reduced fasting plasma hs-CRP (1.28 ± 12.0, -12.5 ± 6.9, 22.5 ± 33.6, -12.2 ± 11.9; 8-week percent change, Mean ± SEM; low LCn3&PP, high LCn3, high PP, high LCn3&PP group, respectively), postprandial 6h-AUC hs-CRP (4.6 ± 16.3, -18.2 ± 7.2, 26.9 ± 35.1, -11.5 ± 11.8, 8-week percent change) and fasting IL-6 (20.8 ± 18.7, -2.44 ± 12.4, 28.1 ± 17.4, -9.6 ± 10.2), IL-17 (2.40 ± 4.9, -13.3 ± 4.9, 3.8 ± 4.43, -11.5 ± 4.7), and VEGF (-5.7 ± 5.8, -5.6 ± 7.5, 3.5 ± 5.8, -11.1 ± 5.5) (8-week percent change; p < 0.05 for LCn3 effect for all; no significant effect for PP; 2-factor ANOVA). An oily fish diet improved subclinical inflammation, while no significant effect was observed for dietary polyphenols.

Evaluation of cardiovascular risk in adults with type 1 diabetes: poor concordance between the 2019 ESC risk classification and 10-year cardiovascular risk prediction according to the Steno Type 1 Risk Engine.

BACKGROUND: Patients with type 1 diabetes (T1D) have higher mortality risk compared to the general population; this is largely due to increased rates of cardiovascular disease (CVD). As accurate CVD risk stratification is essential for an appropriate preventive strategy, we aimed to evaluate the concordance between 2019 European Society of Cardiology (ESC) CVD risk classification and the 10-year CVD risk prediction according to the Steno Type 1 Risk Engine (ST1RE) in adults with T1D. METHODS: A cohort of 575 adults with T1D (272F/303M, mean age 36 ± 12 years) were studied. Patients were stratified in different CVD risk categories according to ESC criteria and the 10-year CVD risk prediction was estimated with ST1RE within each category. RESULTS: Men had higher BMI, WC, SBP than women, while no difference was found in HbA1c levels between genders. According to the ESC classification, 92.5% of patients aged < 35 years and 100% of patients ≥ 35 years were at very high/high risk. Conversely, using ST1RE to predict the 10-year CVD risk within each ESC category, among patients at very high risk according to ESC, almost all (99%) had a moderate CVD risk according to ST1RE if age < 35 years; among patients aged ≥35 years, the majority (59.1%) was at moderate risk and only 12% had a predicted very high risk by ST1RE. The presence of target organ damage or three o more CV risk factors, or early onset T1D of long duration (> 20 years) alone identified few patients (< 30%) among those aged ≥35 years, who were at very high risk according to ESC, in whom this condition was confirmed by ST1RE; conversely, the coexistence of two or more of these criteria identified about half of the patients at high/very high risk also according to this predicting algorithm. When only patients aged ≥ 50 years were considered, there was greater concordance between ESC classification and ST1RE prediction, since as many as 78% of those at high/very high risk according to ESC were confirmed as such also by ST1RE. CONCLUSIONS: Using ESC criteria, a large proportion (45%) of T1D patients without CVD are classified at very high CVD risk; however, among them, none of those < 35 years and only 12% of those ≥ 35 years could be confirmed at very high CVD risk by the ST1RE predicting algorithm. More studies are needed to characterize the clinical and metabolic features of T1D patients that identify those at very high CVD risk, in whom a very aggressive cardioprotective treatment would be justified.

A higher glycemic response to oral glucose is associated with higher plasma apolipoprotein C3 independently of BMI in healthy twins.

BACKGROUND AND AIMS: Plasma apolipoprotein C3 (ApoC3) is associated with higher plasma triglyceride and type 2 diabetes incidence. We evaluated whether body mass index (BMI) or glucose metabolism were associated with ApoC3 in healthy monozygotic (MZ) twins. METHODS AND RESULTS: Forty-seven MZ twin-pairs (20 man, 27 women), aged 23-42 years, were divided in subgroups according to discordance or concordance for (a) BMI (within-pair difference (Δ) in BMI≥3.0 or<3.0 kg/m2), or (b) 2-h glucose iAUC, during oral glucose tolerance test (ΔGlucose iAUC ≥97.5 or<97.5 mmol × 120 minutes). Within these discordant or concordant subgroups, we tested (Wilcoxon signed-rank test) co-twin differences in ApoC3, adiposity measures, insulin-resistance and beta-cell function indices, and plasma and lipoprotein lipids. In BMI-Discordant (p = 0.92) or BMI-Concordant (p = 0.99) subgroups, ApoC3 did not differ between leaner and heavier co-twins. In the Glucose-Discordant subgroup, ApoC3 was significantly higher in twins with higher Glucose iAUC than in their co-twins with the lower Glucose iAUC (10.03 ± 0.78 vs. 8.48 ± 0.52 mg/dl; M ± SE; p = 0.032). Co-twins with higher Glucose iAUC also had higher waist circumference, body fat percentage, liver fat content, worse insulin-sensitivity and beta-cell function and higher cholesterol and triglyceride in plasma VLDL, IDL, and LDL. In Glucose-Concordant twin-pairs, no significant differences were observed in the explored variables. In all twin-pairs, ΔApoC3 correlated with Δ in lipids and glucose metabolism variables, the closest relationship being between ΔApoC3 and ΔVLDL triglyceride (r = 0.74, p < 0.0001). CONCLUSIONS: While ApoC3 was not related to acquired differences in BMI, it associated with early dysregulation of glucose metabolism independently of obesity and genetic background.

Long-term body weight trajectories and metabolic control in type 1 diabetes patients on insulin pump or multiple daily injections: A 10-year retrospective controlled study.

BACKGROUND AND AIMS: Overweight/obesity is a clinical concern also in patients with Type 1 diabetes (T1DM). These patients' body weight may vary depending on whether treatment consists in continuous subcutaneous insulin infusion (CSII) or multiple daily injections (MDI), as these treatments lead to different blood glucose control, insulin doses, and eating behaviors. We compared long-term body weight trajectories in persons with diabetes on CSII or MDI regimens. METHODS AND RESULTS: Annual changes in body weight, HbA1c, and daily insulin doses over 6-10 years were retrospectively analyzed in T1DM adult patients on CSII (n = 90) or MDI (n = 90), strictly matched for sex, age, BMI, and diabetes duration. Mean follow-up was 9.1 ± 1.4 years. Body weight increased linearly (∼0.5 kg per year) throughout the observation period (p = 0.001, repeated measures ANOVA) with no significant difference between the CSII and MDI cohorts (p = 0.74), in either normal-weight or overweight/obese patients. HbA1c over follow-up was lower with CSII than with MDI (p = 0.037), maintaining the initial reduction after starting pump therapy. Insulin doses over follow-up were stably lower than baseline (∼20%) with CSII, while linearly increasing (∼20% from baseline to the end of observation) with MDI (p = 0.002). Mean annual weight changes correlated directly with total insulin dose changes (r = 0.191; p = 0.011) and baseline HbA1c level (r = 0.267; p = 0.001), and inversely with HbA1c changes (-0.173; p = 0.021) and baseline age (r = -0.254; p = 0.001). CONCLUSION: T1DM patients on CSII or MDI showed comparable body weight gain over a 10-year follow-up, despite improved glycemic control and decreased insulin doses with CSII.

Metabolic control and complications in Italian people with diabetes treated with continuous subcutaneous insulin infusion.

BACKGROUND AND AIM: The objective of this cross-sectional study was to evaluate the degree of glycaemic control and the frequency of diabetic complications in Italian people with diabetes who were treated with continuous subcutaneous insulin infusion (CSII). METHODS AND RESULTS: Questionnaires investigating the organisation of diabetes care centres, individuals' clinical and metabolic features and pump technology and its management were sent to adult and paediatric diabetes centres that use CSII for treatment in Italy. Information on standard clinical variables, demographic data and acute and chronic diabetic complications was derived from local clinical management systems. The sample consisted of 6623 people with diabetes, which was obtained from 93 centres. Of them, 98.8% had type 1 diabetes mellitus, 57.2% were female, 64% used a conventional insulin pump and 36% used a sensor-augmented insulin pump. The median glycated haemoglobin (HbA1c) level was 60 mmol/mol (7.6%). The HbA1c target (i.e. <58 mmol/mol for age <18 years and <53 mmol/mol for age >18 years) was achieved in 43.4% of paediatric and 23% of adult participants. Factors such as advanced pump functions, higher rate of sensor use, pregnancy in the year before the study and longer duration of diabetes were associated with lower HbA1c levels. The most common chronic complications occurring in diabetes were retinopathy, microalbuminuria and hypertension. In the year before the study, 5% of participants reported ≥1 episode of severe hypoglycaemic (SH) episodes (SH) and 2.6% reported ≥1 episode of ketoacidosis. CONCLUSIONS: Advanced personal skills and use of sensor-based pump are associated with better metabolic control outcomes in Italian people with diabetes who were treated with CSII. The reduction in SH episodes confirms the positive effect of CSII on hypoglycaemia. CLINICAL TRIAL REGISTRATION NUMBER: NCT 02620917 (ClinicalTrials.gov).

Reduction in liver fat by dietary MUFA in type 2 diabetes is helped by enhanced hepatic fat oxidation.

AIMS/HYPOTHESIS: The aim of this work was to investigate hepatic lipid metabolic processes possibly involved in the reduction of liver fat content (LF) observed in patients with type 2 diabetes after an isoenergetic diet enriched in monounsaturated fatty acids (MUFAs). METHODS: This is an ancillary analysis of a published study. In a parallel-group design, 30 men and eight women, aged 35-70 years, with type 2 diabetes and whose blood glucose was controlled satisfactorily (HbA1c < 7.5% [58 mmol/mol]) by diet or diet plus metformin, were randomised by MINIM software to follow either a high-carbohydrate/high-fibre/low-glycaemic index diet (CHO/fibre diet, n = 20) or a high-MUFA diet (MUFA diet, n = 18) for 8 weeks. The assigned diets were known for the participants and blinded for people doing measurements. Before and after intervention, LF was measured by 1H-MRS (primary outcome) and indirect indices of de novo lipogenesis (DNL) (serum triacylglycerol palmitic:linoleic acid ratio), stearoyl-CoA desaturase activity (SCD-1) (serum triacylglycerol palmitoleic:palmitic acid ratio) and hepatic ß-oxidation of fatty acids (ß-hydroxybutyrate plasma concentrations) were measured. RESULTS: LF was reduced by 30% after the MUFA diet, as already reported. Postprandial ß-hydroxybutyrate incremental AUC (iAUC) was significantly less suppressed after the MUFA diet (n = 16) (-2504 ± 4488 µmol/l × 360 min vs baseline -9021 ± 6489 µmol/l × 360 min) while it was unchanged after the CHO/fibre diet (n = 17) (-8168 ± 9827 µmol/l × 360 min vs baseline -7206 ± 10,005 µmol/l × 360 min, p = 0.962) (mean ± SD, p = 0.043). In the participants assigned to the MUFA diet, the change in postprandial ß-hydroxybutyrate iAUC was inversely associated with the change in LF (r = -0.642, p = 0.010). DNL and SCD-1 indirect indices did not change significantly after either of the dietary interventions. CONCLUSIONS/INTERPRETATION: Postprandial hepatic oxidation of fatty acids is a metabolic process possibly involved in the reduction of LF by a MUFA-rich diet in patients with type 2 diabetes. TRIAL REGISTRATION: ClinicalTrials.gov NCT01025856 FUNDING : The study was funded by Ministero Istruzione Università e Ricerca and Italian Minister of Health.

Polyphenol-rich diets improve glucose metabolism in people at high cardiometabolic risk: a controlled randomised intervention trial.

AIM/HYPOTHESIS: Dietary polyphenols and long chain n-3 polyunsaturated fatty acids (LCn3) are associated with lower cardiovascular risk. This may relate to their influence on glucose metabolism and diabetes risk. We evaluated the effects of diets naturally rich in polyphenols and/or LCn3 of marine origin on glucose metabolism in people at high cardiometabolic risk. METHODS: According to a 2 × 2 factorial design, individuals with high waist circumference and at least one more component of the metabolic syndrome were recruited at the obesity outpatient clinic. Eighty-six participants were randomly assigned by MINIM software to an isoenergetic diet: (1) control, low in LCn3 and polyphenol (analysed n = 20); (2) rich in LCn3 (n = 19); (3) rich in polyphenols (n = 19); or (4) rich in LCn3 and polyphenols (n = 19). The assigned diets were known for the participants and blinded for people doing measurements. Before and after the 8 week intervention, participants underwent a 3 h OGTT and a test meal with a similar composition as the assigned diet for the evaluation of plasma glucose, insulin and glucagon-like peptide 1 (GLP-1) concentrations, and indices of insulin sensitivity and beta cell function. RESULTS: During OGTT, polyphenols significantly reduced plasma glucose total AUC (p = 0.038) and increased early insulin secretion (p = 0.048), while LCn3 significantly reduced beta cell function (p = 0.031) (two-factor ANOVA). Moreover, polyphenols improved post-challenge oral glucose insulin sensitivity (OGIS; p = 0.05 vs control diet by post hoc ANOVA). At test meal, LCn3 significantly reduced GLP-1 total postprandial AUC (p < 0.001; two-factor ANOVA). CONCLUSION/INTERPRETATION: Diets naturally rich in polyphenols reduce blood glucose response, likely by increasing early insulin secretion and insulin sensitivity. These effects may favourably influence diabetes and cardiovascular risk. The implications of the decrease in insulin secretion and postprandial GLP-1 observed with diets rich in marine LCn3 need further clarification. TRIAL REGISTRATION: ClinicalTrials.gov NCT01154478. FUNDING: The trial was funded by European Community's Seventh Framework Programme FP7/2009-2012 under grant agreement FP7-KBBE-222639, Etherpaths Project and 'Ministero Istruzione Università e Ricerca' PRIN 2010-2011 - 2010JCWWKM.

Delayed prandial insulin boluses are an important determinant of blood glucose control and relate to fear of hypoglycemia in people with type 1 diabetes on advanced technologies.

AIMS: Automated insulin delivery systems improve blood glucose control in patients with type 1 diabetes (T1D). However, optimizing their performance requires patient's proper compliance to meal insulin bolus administration. We explored real-life prevalence of delayed prandial boluses (DBs) in adults with T1D on advanced technologies, and their association with glycemic control and fear of hypoglycemia (FH). METHODS: In the last two-week web-based reports of 152 adults with T1D on Hybrid Closed Loop Systems (HCLS) or Sensor Augmented Pump (SAP), DBs were identified when a steep increase in blood glucose occurred at CGM before the prandial bolus, and CGM metrics were evaluated. All participants completed an online questionnaire on FH. RESULTS: Mean DBs over two weeks were 10.2 ± 4.7 (M ± SD, range 1-23) and more frequent in women than men (11.0 ± 4.6 vs. 9.4 ± 4.7, p = 0.036). Participants with more DBs (>12) showed significantly lower Time-In-Range (62.4 ± 13.8 vs. 76.6 ± 9.0 %) than those with less DBs (<7.7), along with higher Time-Above-Range, GMI, and Coefficient-of-Variation (ANOVA, p < 0.001 for all). Participants with higher FH score showed more DBs (11.6 ± 5.0) than those in lower tertiles (9.57 ± 4.59 and 9.47 ± 4.45, ANOVA p = 0.045). CONCLUSIONS: In patients on advanced technologies, delayed boluses are extremely common, and associate with significantly worse glycemic control. Utmost attention is needed to bolus timing, mainly tackling fear of hypoglycemia.

Exploring Nutritional Influence on Blood Glucose Forecasting for Type 1 Diabetes Using Explainable AI.

Type 1 diabetes mellitus (T1DM) is characterized by insulin deficiency and blood sugar control issues. The state-of-the-art solution is the artificial pancreas (AP), which integrates basal insulin delivery and glucose monitoring. However, APs are unable to manage postprandial glucose response (PGR) due to limited knowledge of its determinants, requiring additional information for accurate bolus delivery, such as estimated carbohydrate intake. This study aims to quantify the influence of various meal-related factors on predicting postprandial blood glucose levels (BGLs) at different time intervals (15 min, 60 min, and 120 min) after meals by using deep neural network (DNN) models. The prediction models incorporate preprandial blood glucose values, insulin dosage, and various meal-related nutritional factors such as intake of energy, carbohydrates, proteins, lipids, fatty acids, fibers, glycemic index, and glycemic load as input variables. The impact of input features was assessed by exploiting eXplainable Artificial Intelligence (XAI) methodologies, specifically SHapley Additive exPlanations (SHAP), which provide insights into each feature's contribution to the model predictions. By leveraging XAI methodologies, this study aims to enhance the interpretability and transparency of BGL prediction models and validate clinical literature hypotheses. The findings can aid in the development of decision-support tools for individuals with T1DM, facilitating PGR management and reducing the risks of adverse events. The improved understanding of PGR determinants may lead to advancements in AP technology and improve the overall quality of life for T1DM patients.

Differential Effects of Two Isocaloric Healthy Diets on Postprandial Lipid Responses in Individuals with Type 2 Diabetes.

BACKGROUND: High blood concentrations of triglycerides (TG) in the postprandial period have been shown to be more closely associated with the risk of cardiovascular disease (CVD) than fasting values in individuals with type 2 diabetes (T2D). Dietary changes are the primary determinants of postprandial lipid responses. METHODS: We investigated the effects of an isocaloric multifactorial diet, rich in n-3 PUFA, MUFA, fiber, polyphenols, and vitamins, compared to an isocaloric diet, containing the same amount of MUFA, on the postprandial lipid response in T2D individuals. Following a randomized, controlled, parallel group design, 43 (25 male/18 female) T2D individuals were assigned to an isocaloric multifactorial (n = 21) or a MUFA-rich diet (n = 22). At the beginning and after the 8 weeks of dietary intervention, the concentrations of plasma triglycerides, total cholesterol, HDL cholesterol, and non-HDL cholesterol were detected at fasting and over a 4-h test meal with the same composition as the prescribed diet. RESULTS: The concentrations of fasting plasma triglycerides, total cholesterol, HDL cholesterol, and non-HDL cholesterol did not change after both diets. Compared with the MUFA diet, the 8-week multifactorial diet significantly lowered the postprandial response, which was evaluated as the incremental area under the curve (iAUC), of triglycerides by 33% (64 ± 68 vs. 96 ± 50 mmol/L·240 min, mean ± SD, respectively, p = 0.018), total cholesterol by 105% (-51 ± 33 vs. -25 ± 29, p = 0.013), and non-HDL cholesterol by 206% (-39 ± 33 vs. -13 ± 23, p = 0.013). CONCLUSIONS: In T2D individuals, a multifactorial diet, characterized by several beneficial components, improved the postprandial lipid response compared to a MUFA diet, generally considered a healthy diet being reduced in saturated fat, and probably contributed to the reduction of cardiovascular risk.

Postprandial Glucose Control With Different Hybrid Closed-Loop Systems According to Type of Meal in Adults With Type 1 Diabetes.

BACKGROUND: Hybrid Closed-Loop Systems (HCLs) may not perform optimally on postprandial glucose control. We evaluated how first-generation and advanced HCLs manage meals varying in carbohydrates, fat, and protein. METHOD: According to a cross-sectional design, seven-day food records and HCLs reports from 120 adults with type 1 diabetes (MiniMed670G: n = 40, MiniMed780G: n = 49, Control-IQ [C-IQ]: n = 31) were analyzed. Breakfasts (n = 570), lunches (n = 658), and dinners (n = 619) were divided according to the median of their carbohydrate (g)/fat (g) plus protein (g) ratio (C/FP). After breakfast (4-hour), lunch (6-hour), and dinner (6-hour), continuous glucose monitoring (CGM) metrics and early and late glucose incremental area under the curves (iAUCs) and delivered insulin doses were evaluated. The association of C/FP and HCLs with postprandial glucose and insulin patterns was analyzed by univariate analysis of variance (ANOVA) with a two-factor design. RESULTS: Postprandial glucose time-in-range 70 to 180 mg/dL was optimal after breakfast (78.3 ± 26.9%), lunch (72.7 ± 26.1%), and dinner (70.8 ± 27.3%), with no significant differences between HCLs. Independent of C/FP, late glucose-iAUC after lunch was significantly lower in C-IQ users than 670G and 780G (P < .05), with no significant differences at breakfast and dinner. Postprandial insulin pattern (Ins3-6h minus Ins0-3h) differed by type of HCLs at lunch (P = .026) and dinner (P < .001), being the early insulin dose (Ins0-3h) higher than the late dose (Ins3-6h) in 670G and 780G users with an opposite pattern in C-IQ users. CONCLUSIONS: Independent of different proportions of dietary carbohydrates, fat, and protein, postprandial glucose response was similar in users of different HCLs, although obtained through different automatic insulin delivery patterns.

Intrapancreatic fat deposition and nutritional treatment: the role of various dietary approaches.

Ectopic fat accumulation in various organs and tissues, such as the liver, muscle, kidney, heart, and pancreas, is related to impaired capacity of adipose tissue to accumulate triglycerides, as a consequence of overnutrition and an unhealthy lifestyle. Ectopic fat promotes organ dysfunction and is a key factor in the development and progression of cardiometabolic diseases. Interest in intrapancreatic fat deposition (IPFD) has developed in the last few years, particularly in relation to improvement in methodological techniques for detection of fat in the pancreas, and to growing evidence for the role that IPFD might have in glucose metabolism disorders and cardiometabolic disease. Body weight reduction represents the main option for reducing fat, and the evidence consistently shows that hypocaloric diets are effective in reducing IPFD. Changes in diet composition, independently of changes in energy intake, might offer a more feasible and safe alternative treatment to energy restriction. This current narrative review focused particularly on the possible beneficial role of the diet and its nutrient content, in hypocaloric and isocaloric conditions, in reducing IPFD in individuals with high cardiometabolic risk, highlighting the possible effects of differences in calorie quantity and calorie quality. This review also describes plausible mechanisms by which the various dietary approaches could modulate IPFD.

Gut microbiome and blood glucose control in type 1 diabetes: a systematic review.

Objective: The risk of developing micro- and macrovascular complications is higher for individuals with type 1 diabetes (T1D). Numerous studies have indicated variations in gut microbial composition between healthy individuals and those with T1D. These changes in the gut ecosystem may lead to inflammation, modifications in intestinal permeability, and alterations in metabolites. Such effects can collectively impact the metabolic regulation system, thereby influencing blood glucose control. This review aims to explore the relationship between the gut microbiome, inflammation, and blood glucose parameters in patients with T1D. Methods: Google Scholar, PubMed, and Web of Science were systematically searched from 2003 to 2023 using the following keywords: "gut microbiota," "gut microbiome," "bacteria," "T1D," "type 1 diabetes," "autoimmune diabetes," "glycemic control," "glucose control," "HbA1c," "inflammation," "inflammatory," and "cytokine." The examination has shown 18,680 articles with relevant keywords. After the exclusion of irrelevant articles, seven observational papers showed a distinct gut microbial signature in T1D patients. Results: This review shows that, in T1D patients, HbA1c level was negatively correlated with abundance of Prevotella, Faecalibacterium, and Ruminococcaceae and positively correlated with abundance of Dorea formicigenerans, Bacteroidetes, Lactobacillales, and Bacteriodes. Instead, Bifidobacteria was negatively correlated with fasting blood glucose. In addition, there was a positive correlation between Clostridiaceae and time in range. Furthermore, a positive correlation between inflammatory parameters and gut dysbiosis was revealed in T1D patients. Conclusion: We draw the conclusion that the gut microbiome profiles of T1D patients and healthy controls differ. Patients with T1D may experience leaky gut, bacterial translocation, inflammation, and poor glucose management due to microbiome dysbiosis. Direct manipulation of the gut microbiome in humans and its effects on gut permeability and glycemic control, however, have not been thoroughly investigated. Future research should therefore thoroughly examine other potential pathophysiological mechanisms in larger studies.

Insulin pump therapy in type 1 diabetes is associated with lower indices of Non-Alcoholic Fatty Liver in non-obese women but not men.

AIM: Non-Alcoholic Fatty Liver Disease (NAFLD) is a raising concern in type 1 diabetes (T1D) patients. We evaluated whether multiple daily injections (MDI) or continuous subcutaneous insulin infusion (CSII) may differentially affect NAFLD. METHODS: NAFLD was assessed by Fatty Liver Index (FLI) and Hepatic Steatosis Index (HSI) in 659 T1D patients treated by MDI (n = 414, 65% men) or CSII (n = 245, 50% men) without alcohol abuse or other liver diseases. Clinical and metabolic differences between MDI and CSII participants were also evaluated according to sex. RESULTS: Compared with the MDI cohort, CSII users had a significantly lower FLI (20.2 ± 21.2 vs. 24.8 ± 24.3; p = 0.003), HSI (36.2 ± 4.4 vs. 37.4 ± 4.4; p = 0.003), waist circumference (84.6 ± 11.8 vs. 86.9 ± 13.7 cm; p = 0.026), plasma triglyceride (76.0 ± 45.8 vs. 84.7 ± 58.3 mg/dl; p = 0.035), and daily insulin dose (0.53 ± 0.22 vs. 0.64 ± 0.25 IU/kg body weight; p < 0.001). In CSII users, lower FLI and HSI were observed in women (p = 0.009 and p = 0.033, respectively) but not in men (p = 0.676 and p = 0.131, respectively). Women on CSII also had lower daily insulin doses, plasma triglyceride, and visceral adiposity index than women on MDI. CONCLUSION: CSII is associated with lower NAFLD indices in women with T1D. This may relate to the lower peripheral insulin in the context of a permissive hormonal milieu.