Insulin strategies for dietary fat and protein in type 1 diabetes: A systematic review.

AIM: To identify and report the efficacy of insulin strategies used to manage glycaemia following fat and/or fat and protein meals in type 1 diabetes. METHODS: A systematic literature search of medical databases from 1995 to 2021 was undertaken. Inclusion criteria were randomised controlled trials that reported at least one of the following glycaemic outcomes: mean glucose, area under the curve, time in range or hypoglycaemic episodes. RESULTS: Eighteen studies were included. Thirteen studies gave additional insulin. Five studies gave an additional 30%-43% of the insulin-to-carbohydrate ratio (ICR) for 32-50 g of fat and 31%-51% ICR for 7-35 g of fat with 12-27 g of protein added to control meals. A further eight studies gave -28% to +75% ICR using algorithms based on fat and protein for meals with 19-50 g of carbohydrate, 2-79 g of fat and 10-60 g of protein, only one study reported a glycaemic benefit of giving less than an additional 24% ICR. Eight studies evaluated insulin delivery patterns. Four of six studies in pump therapy, and one of two studies in multiple daily injections showed the combination of bolus and split dose, respectively, were superior. Five studies examined the insulin dose split, four demonstrated 60%-125% ICR upfront was necessary. Two studies investigated the timing of insulin delivery, both reported administration 15 min before the meal lowered postprandial glycaemia. CONCLUSIONS: Findings highlight the glycaemic benefit of an additional 24%-75% ICR for fat and fat and protein meals. For these meals, there is supportive evidence for insulin delivery in a combination bolus with a minimum upfront dose of 60% ICR, 15 min before the meal.

For a high fat, high protein breakfast, preprandial administration of 125% of the insulin dose improves postprandial glycaemic excursions in people with type 1 diabetes using multiple daily injections: A cross-over trial.

AIM: To determine the glycaemic impact of an increased insulin dose, split insulin dose and regular insulin for a high fat, high protein breakfast in people with type 1 diabetes using multiple daily injections (≥4/day). METHODS: In this cross-over trial, participants received the same high fat, high protein breakfast (carbohydrate:30 g, fat:40 g, protein:50 g) for 4 days. Four different insulin strategies were randomly allocated and tested; 100% of the insulin-to-carbohydrate ratio (ICR) given in a single dose using aspart insulin (100Asp), 125% ICR given in a single dose using aspart (125Asp) or regular insulin (125Reg) and 125% ICR given in a split dose using aspart insulin (100:25Asp). Insulin was given 0.25 hr pre-meal and for 100:25Asp, also 1 hr post-meal. Postprandial sensor glucose was measured for 5 hr. RESULTS: In all, 24 children and adults were participated. The 5-hr incremental area under the curves for 100Asp, 125Asp, 125Reg and 100:25Asp were 620 mmol/L.min [95% CI: 451,788], 341 mmol/L.min [169,512], 675 mmol/L.min [504,847] and 434 mmol/L.min [259,608], respectively. The 5-hr incremental area under the curve for 125Asp was significantly lower than for 100Asp (p = 0.016) and for 125Reg (p = 0.002). There was one episode of hypoglycaemia in 125Reg. CONCLUSIONS: For a high fat, high protein breakfast, giving 125% ICR preprandially, using aspart insulin significantly improved postprandial glycaemia without hypoglycaemia. There was no additional glycaemic benefit from giving insulin in a split dose (100:25%) or replacing aspart with regular insulin.

In children and young people with type 1 diabetes using Pump therapy, an additional 40% of the insulin dose for a high-fat, high-protein breakfast improves postprandial glycaemic excursions: A cross-over trial.

AIM: To determine the insulin requirement for a high-fat, high-protein breakfast to optimise postprandial glycaemic excursions in children and young people with type 1 diabetes using insulin pumps. METHODS: In all, 27 participants aged 10-23 years, BMI <95th percentile (2-18 years) or BMI <30 kg/m2 (19-25 years) and HbA1c ≤64 mmol/mol (≤8.0%) consumed a high-fat, high-protein breakfast (carbohydrate: 30 g, fat: 40 g and protein: 50 g) for 4 days. In this cross-over trial, insulin was administered, based on the insulin-to-carbohydrate ratio (ICR) of 100% (control), 120%, 140% and 160%, in an order defined by a randomisation sequence and delivered in a combination bolus, 60% » hr pre-meal and 40% over 3 hr. Postprandial sensor glucose was assessed for 6 hr. RESULTS: Comparing 100% ICR, 140% ICR and 160% ICR resulted in significantly lower 6-hr areas under the glucose curves: mean (95%CI) (822 mmol/L.min [605,1039] and 567 [350,784] vs 1249 [1042,1457], p ≤ 0.001) and peak glucose excursions (4.0 mmol/L [3.0,4.9] and 2.7 [1.7,3.6] vs 6.0 [5.0,6.9],p < 0.001). Rates of hypoglycaemia for 100%-160% ICR were 7.7%, 7.7%, 12% and 19% respectively (p ≥ 0.139). With increasing insulin dose, a step-wise reduction in mean glucose excursion was observed from 1 to 6 hr (p = 0.008). CONCLUSIONS: Incrementally increasing the insulin dose for a high-fat, high-protein breakfast resulted in a predictable, dose-dependent reduction in postprandial glycaemia: 140% ICR improved postprandial glycaemic excursions without a statistically significant increase in hypoglycaemia. These findings support a safe, practical method for insulin adjustment for high-fat, high-protein meals that can be readily implemented in practice to improve postprandial glycaemia.

Subcellular distribution of human tyrosine hydroxylase isoforms 1 and 4 in SH-SY5Y cells.

Tyrosine hydroxylase (TH) is the key enzyme that controls the rate of synthesis of the catecholamines. SH-SY5Y cells with stable transfections of either human tyrosine hydroxylase isoform 1 (hTH1) or human tyrosine hydroxylase isoform 4 (hTH4) were used to determined the subcellular distribution of TH protein and phosphorylated TH, under basal conditions and after muscarine stimulation. Muscarine was previously shown to increase the phosphorylation of only serine 19 and serine 40 in hTH1 cells. Under basal conditions, the hTH1 and hTH4 proteins, their serine 19 phosphorylated forms and hTH1 phosphorylated at serine 40 were all similarly distributed; with ~80% in the cytosolic fraction, ~20% in the membrane fraction, and less than 1%, or not detectable, in the nuclear fraction. However, hTH4 phosphorylated at serine 71 had a significantly different distribution with ~65% cytosolic and ~35% membrane associated. Muscarine stimulation led to hTH1 being redistributed from the cytosol and nuclear fractions to the membrane fraction and hTH4 being redistributed from the cytosol to the nuclear fraction. These muscarine stimulated redistributions were not due to TH phosphorylation at serine 19, serine 40, or serine 71 and were most likely due to TH binding to proteins whose phosphorylation was increased by muscarine. This is the first study to show a difference in subcellular distribution between two human TH isoforms under basal and stimulated conditions.

Modifiable lifestyle risk factors for overweight and obesity in children and adolescents with type 1 diabetes: A systematic review.

This review aims to identify and report epidemiological associations between modifiable lifestyle risk factors for overweight or obesity in children and adolescents with type 1 diabetes (T1D). A systematic literature search of medical databases from 1990 to 2023 was undertaken. Inclusion criteria were observational studies reporting on associations between dietary factors, disordered eating, physical activity, sedentary and sleep behaviours and measures of adiposity in children and adolescents (<18 years) with T1D. Thirty-seven studies met inclusion criteria. Studies were mostly cross-sectional (89 %), and 13 studies included adolescents up to 19 years which were included in this analysis. In adolescents with T1D, higher adiposity was positively associated with disordered eating behaviours (DEB) and a higher than recommended total fat and lower carbohydrate intake. A small amount of evidence suggested a positive association with skipping meals, and negative associations with diet quality and sleep stage. There were no published associations between overweight and physical activity, sedentary behaviours and eating disorders. Overall, the findings infer relationships between DEB, fat and carbohydrate intake and adiposity outcomes in people with T1D. Prospective studies are needed to determine causal relationships and to investigate sleep stages. High quality studies objectively measuring physical activity and include body composition outcomes are needed.

Families' reports of problematic foods, management strategies and continuous glucose monitoring in type 1 diabetes: A cross-sectional study.

AIMS: To identify foods that cause problematic postprandial blood glucose levels (BGLs) in children and young people with type 1 diabetes, the strategies families use to manage these foods and the impact of continuous glucose monitoring (CGM) on nutritional management. METHODS: This was a cross-sectional survey of 100 families attending a paediatric diabetes centre in Australia. RESULTS: Participants (n = 100) had a mean age of 13.0 ± 3.6 years; diabetes duration 5.2 ± 4.0 years; HbA1c 53 ± 0.9 mmol/mol (7.0 ± 0.8%); 52% used multiple daily injections (MDI, ≥4 injections/day); 48% used insulin pump therapy; and overall, 60% used CGM. Ninety-one participants (91%) identified problematic foods, including pizza (60%), pasta (55%) and rice (31%). Of these, 96% used one or more strategies to manage BGLs, including correcting BGLs more often (51%), use of a combination bolus (39%) and increasing the meal insulin dose (32%). Participants who gave additional meal insulin (n = 28) increased the dose by 10% to 25%. All MDI users (n = 15) gave additional insulin pre-prandially. Of those using CGM, 88% (n = 53) reported an increased awareness of the glycaemic impact of foods, and 27% (n = 16) had subsequently made changes to their management including avoiding and/or restricting new foods (n = 7). CONCLUSIONS: Families with type 1 diabetes reported foods such as pizza, pasta and rice as problematic and used strategies such as increasing the insulin dose to minimise their glycaemic impact. CGM contributed to the awareness of problematic foods. Clinicians should discuss these foods and, if challenging, provide targeted strategies including adjusting the insulin dose and delivery pattern to improve postprandial glycaemia.

Screening Practices for Disordered Eating in Paediatric Type 1 Diabetes Clinics.

BACKGROUND: Type 1 Diabetes (T1D) is associated with increased risk of eating disorders. This study aimed to (1) assess adherence of Australasian paediatric T1D clinics to international guidelines on screening for disordered eating and (2) identify barriers and enablers to the use of screening tools for the identification of disordered eating. METHODS: A 24-item survey covering five content domains: clinic characteristics, identification of disordered eating, screening tool use, training and competence, and pathways for referral, was sent to Australasian clinics caring for ≥150 children and adolescents with T1D. RESULTS: Of 13 eligible clinics, 10 participated. Two reported rates of disordered eating of >20%, while eight reported rates < 5%. All clinics used the routine clinical interview as the primary method of screening for disordered eating. Only one used screening tools; these were not diabetes-specific or routinely used. Barriers to use of screening tools included shortage of time and lack of staff confidence around use (n = 7, 70%). Enablers included staff training in disordered eating. CONCLUSIONS: Screening tools for disordered eating are not utilised by most Australasian paediatric T1D clinics. Overall, low reported rates of disordered eating suggest that it may be undetected, potentially missing an opportunity for early intervention.

Global DNA methylation and cognitive and behavioral outcomes at 4 years of age: A cross-sectional study.

BACKGROUND: Accumulating evidence suggests that breastfeeding exclusivity and duration are positively associated with child cognition. This study investigated whether DNA methylation, an epigenetic mechanism modified by nutrient intake, may contribute to the link between breastfeeding and child cognition. The aim was to quantify the relationship between global DNA methylation and cognition and behavior at 4 years of age. METHODS: Child behavior and cognition were measured at age 4 years using the Wechsler Preschool and Primary Scale of Intelligence, third version (WPPSI-III), and Child Behavior Checklist (CBC). Global DNA methylation (%5-methylcytosines (%5mC)) was measured in buccal cells at age 4 years, using an enzyme-linked immunosorbent assay (ELISA) commercial kit. Linear regression models were used to quantify the statistical relationships. RESULTS: Data were collected from 73 children recruited from the Women and Their Children's Health (WATCH) study. No statistically significant associations were found between global DNA methylation levels and child cognition or behavior (p > .05), though the estimates of effect were consistently negative. Global DNA methylation levels in males were significantly higher than in females (median %5mC: 1.82 vs. 1.03, males and females, respectively, (p < .05)). CONCLUSION: No association was found between global DNA methylation and child cognition and behavior; however given the small sample, this study should be pooled with other cohorts in future meta-analyses.

Methyl-Donor and Cofactor Nutrient Intakes in the First 2-3 Years and Global DNA Methylation at Age 4: A Prospective Cohort Study.

BACKGROUND: During the early postnatal period, the impact of nutrition on DNA methylation has not been well studied in humans. The aim was to quantify the relationship between one-carbon metabolism nutrient intake during the first three years of life and global DNA methylation levels at four years. DESIGN: Childhood dietary intake was assessed using infant feeding questionnaires, food frequency questionnaires, 4-day weighed food records and 24-h food records. The dietary records were used to estimate the intake of methionine, folate, vitamins B2, B6 and B12 and choline. The accumulative nutrient intake specific rank from three months to three years of age was used for analysis. Global DNA methylation (%5-methyl cytosines (%5-mC)) was measured in buccal cells at four years of age, using an enzyme-linked immunosorbent assay (ELISA) commercial kit. Linear regression models were used to quantify the statistical relationships. RESULTS: Data were collected from 73 children recruited from the Women and their Children's Health (WATCH) study. No association was found between one-carbon metabolism nutrient intake and global DNA methylation levels (P > 0.05). Global DNA methylation levels in males were significantly higher than in females (median %5-mC: 1.82 vs. 1.03, males and females respectively, (P < 0.05)). CONCLUSION: No association was found between the intake of one-carbon metabolism nutrients during the early postnatal period and global DNA methylation levels at age four years. Higher global DNA methylation levels in males warrants further investigation.