Fasting-Mimicking Diet Promotes Ngn3-Driven ß-Cell Regeneration to Reverse Diabetes.

Stem-cell-based therapies can potentially reverse organ dysfunction and diseases, but the removal of impaired tissue and activation of a program leading to organ regeneration pose major challenges. In mice, a 4-day fasting mimicking diet (FMD) induces a stepwise expression of Sox17 and Pdx-1, followed by Ngn3-driven generation of insulin-producing ß cells, resembling that observed during pancreatic development. FMD cycles restore insulin secretion and glucose homeostasis in both type 2 and type 1 diabetes mouse models. In human type 1 diabetes pancreatic islets, fasting conditions reduce PKA and mTOR activity and induce Sox2 and Ngn3 expression and insulin production. The effects of the FMD are reversed by IGF-1 treatment and recapitulated by PKA and mTOR inhibition. These results indicate that a FMD promotes the reprogramming of pancreatic cells to restore insulin generation in islets from T1D patients and reverse both T1D and T2D phenotypes in mouse models. PAPERCLIP.

Gut microbial metabolites limit the frequency of autoimmune T cells and protect against type 1 diabetes.

Gut dysbiosis might underlie the pathogenesis of type 1 diabetes. In mice of the non-obese diabetic (NOD) strain, we found that key features of disease correlated inversely with blood and fecal concentrations of the microbial metabolites acetate and butyrate. We therefore fed NOD mice specialized diets designed to release large amounts of acetate or butyrate after bacterial fermentation in the colon. Each diet provided a high degree of protection from diabetes, even when administered after breakdown of immunotolerance. Feeding mice a combined acetate- and butyrate-yielding diet provided complete protection, which suggested that acetate and butyrate might operate through distinct mechanisms. Acetate markedly decreased the frequency of autoreactive T cells in lymphoid tissues, through effects on B cells and their ability to expand populations of autoreactive T cells. A diet containing butyrate boosted the number and function of regulatory T cells, whereas acetate- and butyrate-yielding diets enhanced gut integrity and decreased serum concentration of diabetogenic cytokines such as IL-21. Medicinal foods or metabolites might represent an effective and natural approach for countering the numerous immunological defects that contribute to T cell-dependent autoimmune diseases.

Advanced cardiovascular physiology in an individual with type 1 diabetes after 10-year ketogenic diet.

Adults with type 1 diabetes (T1D) have an elevated risk for cardiovascular disease (CVD) compared with the general population. HbA1c is the primary modifiable risk factor for CVD in T1D. Fewer than 1% of patients achieve euglycemia (<5.7% HbA1c). Ketogenic diets (KD; ≤50 g carbohydrate/day) may improve glycemia and downstream vascular dysfunction in T1D by reducing HbA1c and insulin load. However, there are concerns regarding the long-term CVD risk from a KD. Therefore, we compared data collected in a 60-day window in an adult with T1D on exogenous insulin who consumed a KD for 10 years versus normative values in those with T1D (T1D norms). The participant achieved euglycemia with an HbA1c of 5.5%, mean glucose of 98 [5] mg/dL (median [interquartile range]), 90 [11]% time-in-range 70-180 mg/dL (T1D norms: 1st percentile for all), and low insulin requirements of 0.38 ± 0.03 IU/kg/day (T1D norms: 8th percentile). Seated systolic blood pressure (SBP) was 113 mmHg (T1D norms: 18th percentile), while ambulatory awake SBP was 132 ± 15 mmHg (T1D target: <130 mmHg), blood triglycerides were 69 mg/dL (T1D norms: 34th percentile), low-density lipoprotein was 129 mg/dL (T1D norms: 60th percentile), heart rate was 56 beats/min (T1D norms: >1SD below the mean), carotid-femoral pulse wave velocity was 7.17 m/s (T1D norms: lowest quartile of risk), flow-mediated dilation was 12.8% (T1D norms: >1SD above mean), and cardiac vagal baroreflex gain was 23.5 ms/mmHg (T1D norms: >1SD above mean). Finally, there was no indication of left ventricular diastolic dysfunction from echocardiography. Overall, these data demonstrate below-average CVD risk relative to T1D norms despite concerns regarding the long-term impact of a KD on CVD risk.NEW & NOTEWORTHY Adults with type 1 diabetes (T1D) have a 10-fold higher risk for cardiovascular disease (CVD) compared with the general population. We assessed cardiovascular health metrics in an adult with T1D who presented with a euglycemic HbA1c after following a ketogenic diet for the past 10 years. Despite concerns about the ketogenic diet increasing CVD risk, the participant exhibited below-average CVD risk relative to others with T1D when considering all outcomes together.

Adherence to the Dietary Approaches to Stop Hypertension (DASH) diet is associated with lower visceral and hepatic lipid content in recent-onset type 1 diabetes and type 2 diabetes.

AIM: To investigate the associations of the Dietary Approaches to Stop Hypertension (DASH) score with subcutaneous (SAT) and visceral (VAT) adipose tissue volume and hepatic lipid content (HLC) in people with diabetes and to examine whether changes in the DASH diet were associated with changes in these outcomes. METHODS: In total, 335 participants with recent-onset type 1 diabetes (T1D) and type 2 diabetes (T2D) from the German Diabetes Study were included in the cross-sectional analysis, and 111 participants in the analysis of changes during the 5-year follow-up. Associations between the DASH score and VAT, SAT and HLC and their changes were investigated using multivariable linear regression models by diabetes type. The proportion mediated by changes in potential mediators was determined using mediation analysis. RESULTS: A higher baseline DASH score was associated with lower HLC, especially in people with T2D (per 5 points: -1.5% [-2.7%; -0.3%]). Over 5 years, a 5-point increase in the DASH score was associated with decreased VAT in people with T2D (-514 [-800; -228] cm3). Similar, but imprecise, associations were observed for VAT changes in people with T1D (-403 [-861; 55] cm3) and for HLC in people with T2D (-1.3% [-2.8%; 0.3%]). Body mass index and waist circumference changes explained 8%-48% of the associations between DASH and VAT changes in both groups. In people with T2D, adipose tissue insulin resistance index (Adipo-IR) changes explained 47% of the association between DASH and HLC changes. CONCLUSIONS: A shift to a DASH-like diet was associated with favourable VAT and HLC changes, which were partly explained by changes in anthropometric measures and Adipo-IR.

The potential of the Mediterranean diet to improve metabolic control and body composition in youths with Type 1 Diabetes Mellitus.

BACKGROUND: A chronic autoimmune disease with an increasing incidence rate, type 1 diabetes mellitus (T1DM) is typified by the degeneration of the pancreatic beta cells. Diabetes management is significantly impacted by nutrition. Although it has been demonstrated that following the Mediterranean diet (MD) improves metabolic control with type 2 diabetes in children and adults, its effects on children with T1DM have not received much attention. OBJECTIVE: Therefore, the purpose of this study was to assess whether adherence to Mediterranean diet is associated with better metabolic control and body composition in youths with Type 1 Diabetes Mellitus. The study recruited T1DM patients aged 6-18 years at Istanbul University Cerrahpasa Medical Faculty Hospital's Pediatric Endocrinology and Diabetes Outpatient Clinic for follow-up. METHODS: In addition to demographic variables, some anthropometric measurements, body composition and biochemical parameters such as: Trygliceride(TG), Total cholesterol (TC), High density lipoprotein cholesterol (HDL-C), Low density lipoprotein cholesterol (LDL-C), (Aspartate aminotransferase) AST, Alanine transaminase (ALT) and glycated hemoglobin (HbA1c) was analyzed. The time in range (TIR) is a value obtained from continuous glucose monitoring. KIDMED was used to assess the participants' adherence with the MD. RESULTS: Good adherence to the MD resulted in much larger height SDS than poor adherence. Poor adherence to MD resulted in higher body fat than moderate and good adherence. There is positivite correlation between TIR and KIDMED score. Adherence to MD is negatively associated with HbA1c. The regression anaylsis showed that a one-point rise in the KIDMED score would result in a 0.314-unit reduction in the HbA1c value (p < 0.01). CONCLUSIONS: In conclusion, this study found that adhering to MD led to improved anthropometric measurements, biochemistry, and diabetes outcomes. Awareness among children, adolescents with T1DM, and their parents about the benefits of MD compliance for glycemic and metabolic control should be raised.

Vitamin D supplementation induces CatG-mediated CD4+ T cell inactivation and restores pancreatic ß-cell function in mice with type 1 diabetes.

Type 1 diabetes (T1D) is a chronic autoimmune disease accompanied by the immune-mediated destruction of pancreatic ß-cells. In this study, we aimed to explore the regulatory effects of vitamin D (VD) supplementation on pancreatic ß-cell function by altering the expression of bioinformatically identified cathepsin G (CatG) in T1D mice. A T1D mouse model was established in nonobese diabetic (NOD) mice, and their islets were isolated and purified. Pancreatic mononuclear cells (MNCs) were collected, from which CD4+ T cells were isolated. The levels of interleukin (IL)-2, IL-10, tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ) in the supernatant of mouse pancreatic tissue homogenate were assessed using ELISA. Immunohistochemistry and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labelin (TUNEL) staining were conducted to evaluate the effects of VD supplementation on pancreatic tissues of T1D mice. The pancreatic ß-cell line MIN6 was used for in vitro substantiation of findings in vivo. VD supplementation reduced glucose levels and improved glucose tolerance in T1D mice. Furthermore, VD supplementation improved pancreatic ß-cell function and suppressed immunological and inflammatory reactions in the T1D mice. We documented overexpression of CatG in diabetes tissue samples, and then showed that VD supplementation normalized the islet immune microenvironment through downregulating CatG expression in T1D mice. Experiments in vitro subsequently demonstrated that VD supplementation impeded CD4+ T activation by downregulating CatG expression and thereby enhanced pancreatic ß-cell function. Results of the present study elucidated that VD supplementation can downregulate the expression of CatG and inhibit CD4+ T cell activation, thereby improving ß-cell function in T1D.NEW & NOTEWORTHY We report that vitamin D (VD) supplementation downregulates CatG expression and inhibits CD4+ T cell activation, thereby improving ß-cell function in type 1 diabetes (T1D). This study deepens our understanding of the pathogenesis of T1D and clarifies molecular events underlying the alleviatory effect of VD for immunotherapy against T1D.

Administration of Human Derived Upper gut Commensal Prevotella histicola delays the onset of type 1 diabetes in NOD mice.

BACKGROUND: Type 1 diabetes (T1D) is an autoimmune disease that is increasing in prevalence worldwide. One of the contributing factors to the pathogenesis of T1D is the composition of the intestinal microbiota, as has been demonstrated. in T1D patients, with some studies demonstrating a deficiency in their levels of Prevotella. We have isolated a strain of Prevotella histicola from a duodenal biopsy that has anti-inflammatory properties, and in addition, alters the development of autoimmune diseases in mouse models. Therefore, our hypothesis is that the oral administration of P. histicola might delay the development of T1D in the non-obese diabetic (NOD) mice. To assess this, we used the following materials and methods. Female NOD mice (ages 5-8 weeks) were administered every other day P. histicola that was cultured in-house. Blood glucose levels were measured every other week. Mice were sacrificed at various time points for histopathological analysis of the pancreas. Modulation of immune response by the commensal was tested by analyzing regulatory T-cells and NKp46+ cells using flow cytometry and intestinal cytokine mRNA transcript levels using quantitative RT-PCR. For microbial composition, 16 s rRNA gene analysis was conducted on stool samples collected at various time points. RESULTS: Administration of P. histicola in NOD mice delayed the onset of T1D. Beta diversity in the fecal microbiomes demonstrated that the microbial composition of the mice administered P. histicola was different from those that were not treated. Treatment with P. histicola led to a significant increase in regulatory T cells with a concomitant decrease in NKp46+ cells in the pancreatic lymph nodes as compared to the untreated group after 5 weeks of treatment. CONCLUSIONS: These observations suggest that P. histicola treatment delayed onset of diabetes by increasing the levels of regulatory T cells in the pancreatic lymph nodes. This preliminary work supports the rationale that enteral exposure to a non pathogenic commensal P. histicola be tested as a future therapy for T1D.

Mfsd2a overexpression alleviates vascular dysfunction in diabetic retinopathy.

Diabetic retinopathy (DR) is one of the common complications in diabetic patients. Nowadays, VEGF pathway is subject to extensive research. However, about 27% of the patients have a poor visual outcome, with 50% still having edema after two years' treatment of diabetic macular edema (DME) with ranibizumab. Docosahexaenoic acid (DHA), the primary ω-3 long-chain polyunsaturated fatty acid (LC-PUFA), reduces abnormal neovascularization and alleviates neovascular eye diseases. A study reported that fish oil reduced the incidence of retinopathy of prematurity (ROP) by about 27.5% in preterm infants. Although ω-3 LC-PUFAs protects against pathological retinal neovascularization, the treatment effectiveness is low. It is interesting to investigate why DHA therapy fails in some patients. In human vitreous humor samples, we found that the ratio of DHA and DHA-derived metabolites to total fatty acids was higher in vitreous humor from DR patients than that from macular hole patients; however, the ratio of DHA metabolites to DHA and DHA-derived metabolites was lower in the diabetic vitreous humor. The expression of Mfsd2a, the LPC-DHA transporter, was reduced in the oxygen-induced retinopathy (OIR) model and streptozotocin (STZ) model. In vitro, Mfsd2a overexpression inhibited endothelial cell proliferation, migration and vesicular transcytosis. Moreover, Mfsd2a overexpression in combination with the DHA diet obviously reduced abnormal retinal neovascularization and vascular leakage, which is more effective than Mfsd2a overexpression alone. These results suggest that DHA therapy failure in some DR patients is linked to low expression of Mfsd2a, and the combination of Mfsd2a overexpression and DHA therapy may be an effective treatment.

Medical nutrition therapy of pediatric type 1 diabetes mellitus in India: Unique aspects and challenges.

Medical nutrition therapy (MNT) is a vital aspect of management of type 1 diabetes mellitus (T1DM) and should be tailored to ethnic and family traditions and the socioeconomic and educational status of the patient. In this article, we discuss the unique aspects of MNT in children and adolescents with T1DM in the Indian setting, with focus on the challenges faced by patients, dieticians and physicians and how these can be overcome. The authors reviewed the available literature on MNT in T1DM from India and prepared the document based on their vast collective clinical experience in treating patients with T1DM from different regions in India. Indian diets are predominantly carbohydrate-based with high glycemic index (GI) and low protein content. Various methods are available to increase the protein and fiber content and reduce the GI of food in order to limit glycemic excursions. Insulin regimens need to be tailored to the child's school timings, meal schedule, and the availability of a responsible adult to supervise/administer insulin. All patients, irrespective of economic and education background, should be taught the broad principles of healthy eating, balanced diet and carbohydrate counting. There are various barriers to dietary compliance, including joint family system, changing lifestyles, and other factors which need to be addressed. There is a need to customize dietary management according to patient characteristics and needs and develop standardized patient educational material on principles of healthy eating in various regional languages.

Comparison of two carbohydrate intake strategies to improve glucose control during exercise in adolescents and adults with type 1 diabetes.

BACKGROUND AND AIMS: During aerobic physical activity (PA), hypoglycemia is common in people with type 1 diabetes (T1D). Few studies have compared the effectiveness of different carbohydrate (CHO) intake strategies to prevent PA-induced hypoglycemia. Our objective was to compare the efficacy of two CHO intake strategies, same total amount but different CHO intake timing, to maintain glucose levels in the target range (4.0-10.0 mmol/L) during PA in people with T1D. METHODS AND RESULTS: An open-label, randomized, crossover study in 33 participants (21 adults; 12 adolescents). Participants practiced 60 min PA sessions (ergocyle) at 60% VO2peak 3.5 h after lunch comparing an intake of 0.5 g of CHO per kg of body weight applied in a pre-PA single CHO intake (SCI) or in a distributed CHO intake (DCI) before and during PA. The percentage of time spent in glucose level target range during PA was not different between the two strategies (SCI: 75 ± 35%; DCI: 87 ± 26%; P = 0.12). Hypoglycemia (<4.0 mmol/L) occurred in 4 participants (12%) with SCI compared to 6 participants (18%) with DCI (P = 0.42). The SCI strategy led to a higher increase (P = 0.01) and variability of glucose levels (P = 0.04) compared with DCI. CONCLUSIONS: In people living with T1D, for a 60 min moderate aerobic PA in the post-absorptive condition, a 0.5 g/kg CHO intake helped most participants maintain acceptable glycemic control with both strategies. No clinically significant difference was observed between the SCI and DCI strategies. ClinicalTrials.gov Identifier: NCT03214107 (July 11, 2017).

Low Mediterranean Diet scores are associated with reduced kidney function and health related quality of life but not other markers of cardiovascular risk in adults with diabetes and chronic kidney disease.

BACKGROUND AND AIMS: How Mediterranean-style diets impact cardiovascular and health outcomes in patients with diabetes and chronic kidney disease (CKD) is not well known. Our aim was to investigate the association between diet quality, using Mediterranean Diet Scores (MDS) and health outcomes. METHODS AND RESULTS: This is a post-hoc analysis of an RCT and longitudinal study investigating patients with diabetes and CKD. MDS was calculated annually. Scores were analyzed for correlation with lipids, HbA1c, serum potassium, health-related quality of life (HRQOL) and depression. 178 diet records from 50 patients who attended two or more visits were included. Mean MDS was moderate (4.1 ± 1.6) and stable over time. Stage 1-2 vs 3-5 CKD had lower raw MDS (3.8 ± 1.5 vs 4.6 ± 1.5, p < 0.001). Having hyperkalemia was associated with a lower raw MDS scores (3.6 ± 1.6 vs 4.2 ± 1.5, p = 0.03) but not energy adjusted MDS. MDS was not associated with HbA1c or lipids. High vs low MDS was associated with improved HRQOL (mental health 84.4 ± 14.3 vs 80.3 ± 17.1, p < 0.05; general health 62.6 ± 21.0 vs 56.3 ± 19.8, p < 0.001) and fewer depressive symptoms (9.1 ± 7.4 vs 11.7 ± 10.6, p = 0.01). CONCLUSIONS: Low MDS was associated with reduced kidney function and health related quality of life, but not other markers of cardiovascular risk. Further studies are needed to understand the nature and direction of the association between diet quality and disease outcomes in this population.

Hypoglycemic effect of low-sugar juice derived from Hovenia dulcis on type 1 diabetes mellitus rats.

BACKGROUND: Fruit juice is usually rich in monosaccharides and disaccharides. A reverse osmosis separation machine was used to remove monosaccharides and disaccharides from Hovenia dulcis fruit juice, leaving behind most of the bioactive substances in a low-sugar fruit juice (LSFJ), so as to provide a more effective treatment for diabetic patients. METHOD: This study was carried out with type 1 diabetes mellitus model induced with high dose of streptozotocin (60 mg kg-1 ), and oral administration of LSFJ for 4 weeks. RESULTS: LSFJ treatment led to significant gain in body weight and increased serum insulin level, insulin-like growth factor-1 level, blood urea nitrogen level, creatinine level, and hepatic glycogen level. Meanwhile, fasting blood glucose, fructosamine level, and glucose tolerance were also observably enhanced. Additional, LSFJ treatment significantly improved lipid metabolism, islet quality, and islet oxidative stress. The messenger RNA levels of glucose metabolism genes in the pancreas of diabetic rats decreased in the diabetes model group, whereas messenger RNA expression of these genes was significantly increased with LSFJ treatment. CONCLUSION: These findings indicate that LSFJ can improve symptoms associated with type 1 diabetes mellitus. The research also suggests new strategies for diabetes prevention and treatment. © 2021 Society of Chemical Industry.

Dietary fibre and whole grains in diabetes management: Systematic review and meta-analyses.

BACKGROUND: Fibre is promoted as part of a healthy dietary pattern and in diabetes management. We have considered the role of high-fibre diets on mortality and increasing fibre intake on glycaemic control and other cardiometabolic risk factors of adults with prediabetes or diabetes. METHODS AND FINDINGS: We conducted a systematic review of published literature to identify prospective studies or controlled trials that have examined the effects of a higher fibre intake without additional dietary or other lifestyle modification in adults with prediabetes, gestational diabetes, type 1 diabetes, and type 2 diabetes. Meta-analyses were undertaken to determine the effects of higher fibre intake on all-cause and cardiovascular mortality and increasing fibre intake on glycaemic control and a range of cardiometabolic risk factors. For trials, meta regression analyses identified further variables that influenced the pooled findings. Dose response testing was undertaken; Grading of Recommendations Assessment, Development and Evaluation (GRADE) protocols were followed to assess the quality of evidence. Two multicountry cohorts of 8,300 adults with type 1 or type 2 diabetes followed on average for 8.8 years and 42 trials including 1,789 adults with prediabetes, type 1, or type 2 diabetes were identified. Prospective cohort data indicate an absolute reduction of 14 fewer deaths (95% confidence interval (CI) 4-19) per 1,000 participants over the study duration, when comparing a daily dietary fibre intake of 35 g with the average intake of 19 g, with a clear dose response relationship apparent. Increased fibre intakes reduced glycated haemoglobin (HbA1c; mean difference [MD] -2.00 mmol/mol, 95% CI -3.30 to -0.71 from 33 trials), fasting plasma glucose (MD -0.56 mmol/L, 95% CI -0.73 to -0.38 from 34 trials), insulin (standardised mean difference [SMD] -2.03, 95% CI -2.92 to -1.13 from 19 trials), homeostatic model assessment of insulin resistance (HOMA IR; MD -1.24 mg/dL, 95% CI -1.72 to -0.76 from 9 trials), total cholesterol (MD -0.34 mmol/L, 95% CI -0.46 to -0.22 from 27 trials), low-density lipoprotein (LDL) cholesterol (MD -0.17 mmol/L, 95% CI -0.27 to -0.08 from 21 trials), triglycerides (MD -0.16 mmol/L, 95% CI -0.23 to -0.09 from 28 trials), body weight (MD -0.56 kg, 95% CI -0.98 to -0.13 from 18 trials), Body Mass Index (BMI; MD -0.36, 95% CI -0·55 to -0·16 from 14 trials), and C-reactive protein (SMD -2.80, 95% CI -4.52 to -1.09 from 7 trials) when compared with lower fibre diets. All trial analyses were subject to high heterogeneity. Key variables beyond increasing fibre intake were the fibre intake at baseline, the global region where the trials were conducted, and participant inclusion criteria other than diabetes type. Potential limitations were the lack of prospective cohort data in non-European countries and the lack of long-term (12 months or greater) controlled trials of increasing fibre intakes in adults with diabetes. CONCLUSIONS: Higher-fibre diets are an important component of diabetes management, resulting in improvements in measures of glycaemic control, blood lipids, body weight, and inflammation, as well as a reduction in premature mortality. These benefits were not confined to any fibre type or to any type of diabetes and were apparent across the range of intakes, although greater improvements in glycaemic control were observed for those moving from low to moderate or high intakes. Based on these findings, increasing daily fibre intake by 15 g or to 35 g might be a reasonable target that would be expected to reduce risk of premature mortality in adults with diabetes.

Nutrition habits of children and adolescents with type 1 diabetes changed in a 10 years span.

BACKGROUND: Diet plays a key role in the treatment of type 1 diabetes (T1D). Dietary habits changed rapidly in the last decades and few data are available on recent dietary changes in children and adolescents with T1D. OBJECTIVE: To test the hypothesis that diet composition changed in a 10-year period in children and adolescents with T1D. METHODS: Two hundred and twenty-nine T1D subjects (M/F:121/108) aged 6 to 16 years were recruited: 114 (group A) enrolled in 2009, not using CGM and/or CSII, and 115 (group B) enrolled in 2019. Anthropometric biochemical (HbA1c, lipid profile), diet, and insulin therapy parameters were compared between the two groups. Multivariate logistic regression analysis was performed with HbA1c as dependent variable (HbA1c > 58 mmol/mol = 1) and nutritional variables and technology use as independent ones. RESULTS: Energy intake of group A was not statistically different from that of group B. Group B had a significantly (P < 0.001) higher protein and lipids intake and lower total carbohydrate and fiber intake than group A. HbA1c was significantly (P < 0.01) lower in group B than in group A. Logistic regression analysis showed that MUFA (OR 0.83, 95%CI:0.693-0.998), fiber intake (OR 0.82, 95%CI:0.699-0.0969), and technology use (OR 0.15, 95%CI:0.031-0.685), adjusted for age, gender, BMI, energy intake and diabetes duration, were associated with a HbA1c higher than 58 mmol/mol) (R2 = 0.27, P < 0.05). CONCLUSIONS: In a 10-year period, diet composition of children and adolescents with T1D changed and glucometabolic control improved. Fiber and MUFA intake showed a positive effect on HbA1c, independent from technology use, supporting the importance of educating children with T1D and families to maintain healthy eating habits.

The current state of parent feeding behavior, child eating behavior, and nutrition intake in young children with type 1 diabetes.

BACKGROUND: One integral component of type 1 diabetes (T1D) management is attention to nutrition, which can be particularly challenging in young children. OBJECTIVE: The current study reports on parent and child eating/feeding behavior and nutrition intake as compared with current recommendations for pediatric T1D. SUBJECTS: Participants were 46 children ages 2 to 5 diagnosed with T1D and one parent. METHODS: The Behavioral Pediatrics Feeding Assessment Scale (BPFAS) was used to assess parent feeding and child eating behaviors. The Remote Food Photography Method (RFPM) was used to analyze nutrition intake at breakfast. Demographic and medical information were collected via self-report and medical chart review. RESULTS: In the current sample, 37% of BPFAS scores were above the cutoff for problem child eating behavior. Only 28% of participants met the recommended goals for glycemic control (hemoglobin A1c, HbA1c < 7.5). Children who did not meet glycemic control targets reported higher carbohydrate intake than those meeting targets. Protein recommendations were met by 46%; 22.7% met the recommendation for carbohydrate intake, and 45.5% met fat intake recommendations. The majority of the sample did not meet body mass index percentile (BMI%) recommendations with 51% having a BMI% above the 85th percentile. CONCLUSIONS: Many parents of young children with T1D report problem child eating behaviors. Further, a significant number of young children are not meeting glycemic, nutritional, or BMI guidelines for T1D. Routine screening for dietary difficulties in young children is warranted. Future research should aim to examine interventions targeting families with young children not meeting nutrition, glycemic, or BMI guidelines.

Gluten-free diet impact on dynamics of pancreatic islet-specific autoimmunity detected at celiac disease diagnosis.

OBJECTIVE: Almost 6% of celiac disease (CD) patients at diagnosis are positive for at least one of the main pancreatic islet autoantibodies that characterize type 1 diabetes (T1D). Few information, dated back to almost two decades ago, exist as to whether a gluten-free diet (GFD) could reduce the islet-specific autoimmunity detected in patients at CD diagnosis. Aim of the study was to evaluate the impact of GFD on 31 patients who presented islet-specific autoimmunity at CD diagnosis. METHODS: CD patient sera collected at diagnosis and throughout the GFD were analyzed for the main humoral autoantibodies so far identified in T1D, directed against one or more among insulin, glutamic-acid decarboxylase, tyrosine-phosphatase 2, and zinc cation-efflux transporter autoantigens. RESULTS: GFD (median duration 39 months) was associated to a decrease or disappearance of the islet-specific autoantibodies in 71% of CD patients. Almost 80% of the patients who became autoantibody-negative during the GFD were positive for only one of the islet-specific autoimmune markers at CD diagnosis, with none of them developing diabetes. Conversely, 80% of the CD patients positive at diagnosis for ≥2 islet-specific autoantibodies were still positive after more than two years of GFD, with 25% of them developing T1D. CONCLUSIONS: Various factors appear to influence, individually or in combination, the effects of the GFD on pancreatic islet-specific autoimmune response detected at CD diagnosis. These factors include the number of diabetes autoantibodies found at CD diagnosis, the adherence to the GFD, its duration and an asymptomatic clinical presentation of CD.

Non-nutritive sweeteners for diabetes mellitus.

BACKGROUND: Products sweetened with non-nutritive sweeteners (NNS) are widely available. Many people with type 1 or type 2 diabetes use NNS as a replacement for nutritive sweeteners to control their carbohydrate and energy intake. Health outcomes associated with NNS use in diabetes are unknown. OBJECTIVES: To assess the effects of non-nutritive sweeteners in people with diabetes mellitus. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE Ovid, Scopus, the WHO ICTRP, and ClinicalTrials.gov. The date of the last search of all databases (except for Scopus) was May 2019. We last searched Scopus in January 2019. We did not apply any language restrictions. SELECTION CRITERIA: We included randomised controlled trials (RCTs) with a duration of four weeks or more comparing any type of NNS with usual diet, no intervention, placebo, water, a different NNS, or a nutritive sweetener in individuals with type 1 or type 2 diabetes. Trials with concomitant behaviour-changing interventions, such as diet, exercise, or both, were eligible for inclusion, given that the concomitant interventions were the same in the intervention and comparator groups. DATA COLLECTION AND ANALYSIS: Two review authors independently screened abstracts, full texts, and records retrieved from trials registries, assessed the certainty of the evidence, and extracted data. We used a random-effects model to perform meta-analysis, and calculated effect estimates as risk ratios (RRs) for dichotomous outcomes and mean differences (MDs) for continuous outcomes, using 95% confidence intervals (CIs). We assessed risk of bias using the Cochrane 'Risk of bias' tool and the certainty of evidence using the GRADE approach. MAIN RESULTS: We included nine RCTs that randomised a total of 979 people with type 1 or type 2 diabetes. The intervention duration ranged from 4 to 10 months. We judged none of these trials as at low risk of bias for all 'Risk of bias' domains; most of the included trials did not report the method of randomisation. Three trials compared the effects of a dietary supplement containing NNS with sugar: glycosylated haemoglobin A1c (HbA1c) was 0.4% higher in the NNS group (95% CI -0.5 to 1.2; P = 0.44; 3 trials; 72 participants; very low-certainty evidence). The MD in weight change was -0.1 kg (95% CI -2.7 to 2.6; P = 0.96; 3 trials; 72 participants; very low-certainty evidence). None of the trials with sugar as comparator reported on adverse events. Five trials compared NNS with placebo. The MD for HbA1c was 0%, 95% CI -0.1 to 0.1; P = 0.99; 4 trials; 360 participants; very low-certainty evidence. The 95% prediction interval ranged between -0.3% and 0.3%. The comparison of NNS versus placebo showed a MD in body weight of -0.2 kg, 95% CI -1 to 0.6; P = 0.64; 2 trials; 184 participants; very low-certainty evidence. Three trials reported the numbers of participants experiencing at least one non-serious adverse event: 36/113 participants (31.9%) in the NNS group versus 42/118 participants (35.6%) in the placebo group (RR 0.78, 95% CI 0.39 to 1.56; P = 0.48; 3 trials; 231 participants; very low-certainty evidence). One trial compared NNS with a nutritive low-calorie sweetener (tagatose). HbA1c was 0.3% higher in the NNS group (95% CI 0.1 to 0.4; P = 0.01; 1 trial; 354 participants; very low-certainty evidence). This trial did not report body weight data and adverse events. The included trials did not report data on health-related quality of life, diabetes complications, all-cause mortality, or socioeconomic effects. AUTHORS' CONCLUSIONS: There is inconclusive evidence of very low certainty regarding the effects of NNS consumption compared with either sugar, placebo, or nutritive low-calorie sweetener consumption on clinically relevant benefit or harm for HbA1c, body weight, and adverse events in people with type 1 or type 2 diabetes. Data on health-related quality of life, diabetes complications, all-cause mortality, and socioeconomic effects are lacking.

Complex dietary polysaccharide modulates gut immune function and microbiota, and promotes protection from autoimmune diabetes.

The dietary supplement and prebiotic values of ß-glucan-rich products have been widely recognized and dietary approaches for modulating autoimmunity have been increasingly explored, we assess the impact of oral administration of high-purity yeast ß-glucan (YBG) on gut immune function, microbiota and type 1 diabetes (T1D) using mouse models. Oral administration of this non-digestible complex polysaccharide caused a dectin-1-dependent immune response involving increased expression of interleukin-10 (IL-10), retinaldehyde dehydrogenase (Raldh) and pro-inflammatory cytokines in the gut mucosa. YBG-exposed intestinal dendritic cells induced/expanded primarily Foxp3+ , IL-10+ and IL-17+ T cells, ex vivo. Importantly, prolonged oral administration of low-dose YBG at pre-diabetic stage suppressed insulitis and significantly delayed the appearance of T1D in non-obese diabetic (NOD) mice. Further, prolonged treatment with YBG showed increased Foxp3+ T-cell frequencies, and a significant change in the gut microbiota, particularly an increase in the abundance of Bacteroidetes and a decrease in the Firmicute members. Oral administration of YBG, together with Raldh-substrate and ß-cell antigen, resulted in better protection of NOD mice from T1D. These observations suggest that YBG not only has a prebiotic property, but also an oral tolerogenic-adjuvant-like effect, and these features could be exploited for modulating autoimmunity in T1D.

Glycaemic stability of a cyclist with Type 1 diabetes: 4011 km in 20 days on a ketogenic diet.

BACKGROUND: Maintaining glycaemic control during exercise presents a significant challenge for people living with Type 1 diabetes. Significant glycaemic variability has been observed in athletes with Type 1 diabetes in competitive contexts. While very-low-carbohydrate ketogenic diets have been shown to minimize glycaemic excursions, no published data have examined if this translates to exercise. CASE REPORT: We report the case of a 37-year-old man with Type 1 diabetes who successfully undertook a 4011 km cycle across Australia over 20 consecutive days whilst consuming a very-low-carbohydrate ketogenic diet. Continuous glucose monitoring data capture was 98.4% for the ride duration and showed remarkable glycaemic stability, with a standard deviation of 2.1 mmol/l (average interstitial glucose 6.1 mmol/l) and 80.4% of time spent within a range of 3.9-10 mmol/l. Interstitial glucose was <3 mmol/l for 2.1% of this time, with only a single episode of symptomatic hypoglycaemia prompting brief interruption of exercise for carbohydrate administration. CONCLUSION: This case demonstrates the viability of a very-low-carbohydrate ketogenic diet in an individual with Type 1 diabetes undertaking exercise. While the effect of a very-low-carbohydrate ketogenic diet is yet to be examined more broadly in athletes with Type 1 diabetes, the glycaemic stability observed suggests that fat adaptation may attenuate glycaemic swings and reduce reliance on carbohydrate consumption during exercise for maintaining euglycaemia.

The ups and downs of low-carbohydrate diets in the management of Type 1 diabetes: a review of clinical outcomes.

Dietary management has been a mainstay of care in Type 1 diabetes since before the discovery of insulin when severe carbohydrate restriction was advocated. The use of insulin facilitated re-introduction of carbohydrate into the diet. Current management guidelines focus on a healthy and varied diet with consideration of glycaemic load, protein and fat. As a result of frustration with glycaemic outcomes, low-carbohydrate diets have seen a resurgence in popularity. To date, low-carbohydrate diets have not been well studied in the management of Type 1 diabetes. Studies looking at glycaemic outcomes from low-carbohydrate diets have largely been cross-sectional, without validated dietary data and with a lack of control groups. The participants have been highly motivated self-selected individuals who follow intensive insulin management practices, including frequent blood glucose monitoring and additional insulin corrections with tight glycaemic targets. These confounders limit the ability to determine the extent of the impact of dietary carbohydrate restriction on glycaemic outcomes. Carbohydrate-containing foods including grains, fruit and milk are important sources of nutrients. Hence, low-carbohydrate diets require attention to vitamin and energy intake to avoid micronutrient deficiencies and growth issues. Adherence to restricted diets is challenging and can have an impact on social normalcy. In individuals with Type 1 diabetes, adverse health risks such as diabetic ketoacidosis, hypoglycaemia, dyslipidaemia and glycogen depletion remain clinical concerns. In the present paper, we review studies published to date and provide clinical recommendations for ongoing monitoring and support for individuals who choose to adopt a low-carbohydrate diet. Strategies to optimize postprandial glycaemia without carbohydrate restriction are presented.