Protein and fat meal content increase insulin requirement in children with type 1 diabetes - Role of duration of diabetes.
ABSTRACT: Hyperglycaemia remains a challenge in type 1 diabetes since current regimes used to determine meal insulin requirements prove to be ineffective. This is particularly problematic for meals containing high amounts of protein and fat. We aimed to determine the post-prandial glycaemic response and total insulin need for mixed meals, using sensor-augmented insulin pumps in children with type 1 diabetes.Twenty-two children with type 1 diabetes, aged 4-17?years on insulin pump therapy completed this home-based, cross-over, randomised controlled trial. Two meals with identical carbohydrate content - one with low fat and protein (LFLP) and one with high fat and protein (HFHP) contents - were consumed using normal insulin boluses. Blood glucose monitoring was done for 10?h post-meal, with correction bolus insulin given two-hourly if required.The HFHP meal required significantly more total insulin (3.48 vs. 2.7 units) as a result of increased post-meal correction insulin requirement (1.2 vs. 0.15 units) spread over a longer duration (6 vs. 3?h). The HFHP meals significantly increased the time spent above target glucose level. Duration of diabetes and total daily insulin use significantly influenced the post-prandial blood glucose response to the two meals.When consuming carbohydrate-based mixed meals, children with type 1 diabetes on insulin pump therapy, required significantly more insulin over a longer period of time than the insulin requirement calculated using current regimes. This additional amount required is influenced by the duration of diabetes and total daily insulin use.
Project description:BACKGROUND: Although the effects of resistant starch (RS) on postprandial glycemia and insulinemia have been extensively studied, little is known about the impact of RS on fat metabolism. This study examines the relationship between the RS content of a meal and postprandial/post-absorbative fat oxidation. RESULTS: 12 subjects consumed meals containing 0%, 2.7%, 5.4%, and 10.7% RS (as a percentage of total carbohydrate). Blood samples were taken and analyzed for glucose, insulin, triacylglycerol (TAG) and free fatty acid (FFA) concentrations. Respiratory quotient was measured hourly. The 0%, 5.4%, and 10.7% meals contained 50 muCi [1-14C]-triolein with breath samples collected hourly following the meal, and gluteal fat biopsies obtained at 0 and 24 h. RS, regardless of dose, had no effect on fasting or postprandial insulin, glucose, FFA or TAG concentration, nor on meal fat storage. However, data from indirect calorimetry and oxidation of [1-14C]-triolein to 14CO2 showed that addition of 5.4% RS to the diet significantly increased fat oxidation. In fact, postprandial oxidation of [1-14C]-triolein was 23% greater with the 5.4% RS meal than the 0% meal (p = 0.0062). CONCLUSIONS: These data indicate that replacement of 5.4% of total dietary carbohydrate with RS significantly increased post-prandial lipid oxidation and therefore could decrease fat accumulation in the long-term.
Project description:Aims:To evaluate the pharmacokinetics and pharmacodynamics of basal insulin glargine with mealtime insulin glulisine or twice daily 75/25 premixed neutral protamine insulin lispro and insulin lispro in individuals with type 1 diabetes during three standardized meals over a 24 hour duration and compare to physiologic insulin and glucose responses in healthy non-diabetic individuals. Methods:Twelve healthy (4 male/8 female) and thirteen individuals with type 1 diabetes (8 male/5 female) were studied during three sequential standardized meals. Individuals with type 1 diabetes received either glargine and glulisine injected 5 minutes subcutaneously before each meal or premixed insulin lispro injected 5 minutes before breakfast and dinner in a randomized fashion separated by eight weeks. Results:The incremental systemic insulin AUC, maximal insulin concentration, and rate of rise of systemic insulin (0-30 minutes) during all three meal intervals were similar between glargine/glulisine and healthy controls. Incremental glucose AUC with glargine/glulisine was similar to controls at lunch and dinner. With premix 75/25 insulin, insulin AUC was lower and incremental glucose AUC was greater at lunch compared to the healthy and glargine/glulisine. Hypoglycemic events before lunch were greater with premix insulin group than with glargine/glulisine (p?<?0.0001). Conclusions:Glargine/glulisine pharmacokinetics in type 1 diabetes can closely approximate physiologic insulin responses in healthy individuals during a day in which three standardized meals are consumed. Additionally, when glulisine is dosed only five minutes pre-meal, systemic insulin concentration rises as rapidly as prandial endogenous insulin levels. This present study compared glargine and glulisine administered in an approximate 50/50 proportion. Future studies of alternate meal times, meal content and differing premixed insulin preparations are indicated.
Project description:Post-prandial hyperglycemia is still a challenging issue in intensified insulin therapy. Data of 35 T1D patients during a four-week period were analyzed: RT-CGM (real time continuous glucose monitoring) record, insulin doses, diet (including meal photos), energy expenditure, and other relevant conditions. Patients made significant errors in carbohydrate counting (in 56% of cooked and 44% of noncooked meals), which resulted in inadequate insulin doses. Subsequently, a mobile application was programmed to provide individualized advice on prandial insulin dose. When using the application, a patient chooses only the type of categorized situation (e.g., meals with other relevant data) without carbohydrates counting. The application significantly improved postprandial glycemia as normoglycemia was reached in 95/105 testing sessions. Other important findings of the study include: A high intake of saturated fat (median: 162% of recommended intake); a low intake of fiber and vitamin C (median: 42% and 37%, respectively, of recommended intake); an increase in overweight/obesity status (according to body fat measurement), especially in women (median of body fat: 30%); and low physical activity (in 16/35 patients). The proposed individualized approach without carbohydrate counting may help reach postprandial normoglycemia but it is necessary to pay attention to the lifestyle habits of T1D patients too.
Project description:To determine if a regimen with prandial + basal insulin compared with basal insulin attenuates post-meal inflammatory and glycative biomarkers in patients with Type 2 diabetes.This test-meal sub-study in the USA is from a previously reported clinical trial comparing the effect on glycaemic control of 24 weeks of thrice-daily pre-meal insulin lispro mix 50 (50% insulin lispro, 50% insulin lispro protamine suspension) or bedtime insulin glargine, both plus metformin. In the sub-study, glucose, insulin, triglycerides, high-sensitivity C-reactive protein, tumour necrosis factor ?, interleukin-6, methylglyoxal and 3-deoxyglucosone were measured during the post-meal period of a mixed-meal breakfast at the final visit. Prandial + basal (n = 25) and basal (n = 21) insulin were administered at the same times as during the previous 24 weeks.Post-meal, the prandial + basal insulin group had significantly higher insulin, lower glucose and triglycerides, as well as lower high-sensitivity C-reactive protein, tumour necrosis factor ? and interleukin-6, than the basal insulin group. Glucose incremental area under the concentration curve significantly correlated with high-sensitivity C-reactive protein, tumour necrosis factor ?, interleukin-6, methylglyoxal and 3-deoxyglucosone incremental area under the concentration curve. Insulin incremental area under the concentration curve correlated inversely with high-sensitivity C-reactive protein and tumour necrosis factor ? incremental area under the concentration curve. However, after adjusting for glucose incremental area under the concentration curve, these inverse correlations were no longer significant. Triglyceride incremental area under the concentration curve was not correlated with any biomarker incremental area under the concentration curve.Controlling post-meal hyperglycaemia with prandial + basal insulin in patients with Type 2 diabetes attenuates meal-induced increases in high-sensitivity C-reactive protein, interleukin-6 and tumour necrosis factor ? compared with basal insulin. The rise in post-meal glucose, but not triglycerides, significantly correlated with the rise in post-meal inflammatory and glycative biomarkers.
Project description:Overfeeding high-fat (HF) meals results in both short-term and long-term effects that vary depending upon adiposity status (obese vs nonobese) and family history of type 2 diabetes. Although more than 4 weeks of overeating produces mild insulin resistance, whether the same is true of a single, HF meal is not clear. We reviewed overfeeding studies of 4-8 weeks duration, studies of single HF meals and our own (unpublished) plasma insulin and glucose concentration data from 59 nonobese and 15 overweight/obese volunteers who consumed either a normal-fat (NF) breakfast or a breakfast matched for carbohydrate and protein, but with an additional 80 g of monounsaturated fat (HF). Four to eight weeks of overfeeding a HF diet causes an ∼10% reduction in insulin sensitivity. Some authors report that a single HF meal is associated with greater postprandial insulin concentrations, whereas other investigators have not confirmed such a response. We found that plasma glucose concentrations peaked later following a HF breakfast than a NF breakfast in both obese and nonobese adults and that daytime plasma insulin concentrations were not uniformly increased following a HF breakfast. We conclude that a single HF meal delays the postprandial peak in glucose concentrations, likely due to delayed gastric emptying. This will confound attempts to use insulinemia as a marker of insulin resistance. After 4-8 weeks of overeating a HF diet accompanied by 2-4 kg of fat gain, insulin sensitivity decreases by ∼10%. Although we could not demonstrate that baseline insulin resistance predicts visceral fat gain with overfeeding, normal-weight relatives of type 2 diabetes mellitus do tend to gain more weight and become more insulin resistant than those without a positive family history of type 2 diabetes mellitus. In summary, short-term weight gain from HF diets induces relatively mild metabolic disorders.
Project description:Traditionally, insulin bolus calculations for managing postprandial glucose levels in individuals with type 1 diabetes rely solely on the carbohydrate content of a meal. However, recent studies have reported that other macronutrients in a meal can alter the insulin required for good postprandial control. Specifically, studies have shown that high-fat (HF) meals require more insulin than low-fat (LF) meals with identical carbohydrate content. Our objective was to assess the mechanisms underlying the higher insulin requirement observed in one of these studies.We used a combination of previously validated metabolic models to fit data from a study comparing HF and LF dinners with identical carbohydrate content in seven subjects with type 1 diabetes. For each subject and dinner type, we estimated the model parameters representing the time of peak meal-glucose appearance (?(m)), insulin sensitivity (S(I)), the net hepatic glucose balance, and the glucose effect at zero insulin in four time windows (dinner, early night, late night, and breakfast) and assessed the differences in model parameters via paired Wilcoxon signed-rank tests.During the HF meal, the ?(m) was significantly delayed (mean and standard error [SE]: 102  min vs. 71  min; P?=?0.02), and S(I) was significantly lower (7.25?×?10(-4) [1.29?×?10(-4)] mL/?U/min vs. 8.72?×?10(-4) [1.08?×?10(-4)] mL/?U/min; P?=?0.02).In addition to considering the putative delay in gastric emptying associated with HF meals, we suggest that clinicians reviewing patient records consider that the fat content of these meals may alter S(I).
Project description:To evaluate safety, efficacy and glucose turnover during closed-loop with meal announcement using reduced prandial insulin boluses in adolescents with type 1 diabetes (T1D).We conducted a randomized crossover study comparing closed-loop therapy with standard prandial insulin boluses versus closed-loop therapy with prandial boluses reduced by 25%. Eight adolescents with T1D [3 males; mean (standard deviation) age 15.9 (1.5) years, glycated haemoglobin 74 (17) mmol/mol; median (interquartile range) total daily dose 0.9 (0.7, 1.1) IU/kg/day] were studied on two 36-h-long visits. In random order, subjects received closed-loop therapy with either standard or reduced insulin boluses administered with main meals (50-80 g carbohydrates) but not with snacks (15-30 g carbohydrates). Stable-label tracer dilution methodology measured total glucose appearance (Ra_total) and glucose disposal (Rd).The median (interquartile range) time spent in target (3.9-10 mmol/l) was similar between the two interventions [74 (66, 84)% vs 80 (65, 96)%; p = 0.87] as was time spent above 10 mmol/l [21.8 (16.3, 33.5)% vs 18.0 (4.1, 34.2)%; p = 0.87] and below 3.9 mmol/l [0 (0, 1.5)% vs 0 (0, 1.8)%; p = 0.88]. Mean plasma glucose was identical during the two interventions [8.4 (0.9) mmol/l; p = 0.98]. Hypoglycaemia occurred once 1.5 h post-meal during closed-loop therapy with standard bolus. Overall insulin delivery was lower with reduced prandial boluses [61.9 (55.2, 75.0) vs 72.5 (63.6, 80.3) IU; p = 0.01] and resulted in lower mean plasma insulin concentration [186 (171, 260) vs 252 (198, 336) pmol/l; p = 0.002]. Lower plasma insulin was also documented overnight [160 (136, 192) vs 191 (133, 252) pmol/l; p = 0.01, pooled nights]. Ra_total was similar [26.3 (21.9, 28.0) vs 25.4 (21.0, 29.2) µmol/kg/min; p = 0.19] during the two interventions as was Rd [25.8 (21.0, 26.9) vs 25.2 (21.2, 28.8) µmol/kg/min; p = 0.46].A 25% reduction in prandial boluses during closed-loop therapy maintains similar glucose control in adolescents with T1D whilst lowering overall plasma insulin levels. It remains unclear whether closed-loop therapy with a 25% reduction in prandial boluses would prevent postprandial hypoglycaemia.
Project description:BACKGROUND:Whole-grain intake is associated with lower risk of type 2 diabetes but the mechanisms are unclear. PURPOSE:We tested the hypothesis that a WG diet reduces insulin resistance and improves glucose use in individuals at risk for type 2 diabetes compared with an isocaloric-matched refined-grain diet. METHODS:A double-blind, randomized, controlled, crossover trial of 14 moderately obese adults (Age, 38?±?2?y; BMI, 34.0?±?1.1?kg/m2). Insulin resistance and glucose metabolism was assessed using an oral glucose tolerance test combined with isotopic tracers of [6,6-2H2]-glucose and [U-13C]-glucose, and indirect calorimetry. Peripheral and hepatic insulin resistance was assessed as 1/(rate of disposal/insulin), and endogenous glucose rates of appearance (Ra) iAUC60-240?×?insulin iAUC60-240, respectively. Both diets met ADA nutritional guidelines and contained either whole-grain (50?g per 1000?kcal) or equivalent refined-grain. All food was provided for 8?wk. with an 8-10?wk. washout period between diets. RESULTS:Post-prandial glucose tolerance, peripheral insulin sensitivity, and metabolic flexibility (insulin-stimulated - fasting carbohydrate oxidation) improvements were greater after whole-grain compared to the refined-grain diet (P?<?0.05). Compared to baseline, body fat (~2?kg) and hepatic Ra insulin resistance was reduced by both diets, while fasting glucose and exogenous glucose-meal were unchanged after both interventions. Changes in peripheral insulin resistance and metabolic flexibility correlated with improved glucose tolerance (P?<?0.05). CONCLUSION:Whole-grains reduced diabetes risk and the mechanisms appear to work through reduced post-prandial blood glucose and peripheral insulin resistance that were statistically linked to enhanced metabolic flexibility.
Project description:BACKGROUND:Green tea extract (GTE) may be involved in a favourable post-prandial response to high-carbohydrate meals. The catechol-O-methyltransferase (COMT) genotype may modify these effects. We examined the acute effects of GTE supplementation on the post-prandial response to a high-carbohydrate meal by assessing appetite-associated hormones and glucose homeostasis marker concentrations in women who consumed 843 mg of (-)-epigallocatechin-3-gallate (EGCG) or placebo capsules for 11-12 months. METHODS:Sixty Caucasian post-menopausal women (body mass index ? 25.0 kg m-2 ) were included in a randomised, double-blind feeding study. GTE was consumed with a breakfast meal [2784.0 kJ (665.4 kcal); 67.2% carbohydrate]. Blood samples were drawn pre-meal, post-meal, and every 30 min for 4 h. Participants completed six satiety questionnaires. RESULTS:Plasma leptin, ghrelin and adiponectin did not differ between GTE and placebo at any time point; COMT genotype did not modify these results. Participants randomised to GTE with the high-activity form of COMT (GTE-high COMT) had higher insulin concentrations at time 0, 0.5 and 1.0 h post-meal compared to all COMT groups randomised to placebo. Insulin remained higher in the GTE-high COMT group at 1.5, 2.0 and 2.5 h compared to Placebo-low COMT (P < 0.02). GTE-high COMT had higher insulin concentrations at times 0, 0.5, 1.0, 1.5 and 2.0 h compared to the GTE-low COMT (P ? 0.04). Area under the curve measurements of satiety did not differ between GTE and placebo. CONCLUSIONS:GTE supplementation and COMT genotype did not alter acute post-prandial responses of leptin, ghrelin, adiponectin or satiety, although it may be involved in post-meal insulinaemic response of overweight and obese post-menopausal women.
Project description:Prandial insulin dosing is an empirical practice associated frequently with poor reproducibility in postprandial glucose response. Based on continuous glucose monitoring (CGM), a method for prandial insulin administration (iBolus) is presented and evaluated for people with type 1 diabetes using CSII therapy.An individual patient's model for a 5-h postprandial period was obtained from 6-day ambulatory CGM and used for iBolus calculation in 12 patients with type 1 diabetes. In a double-blind, crossover study each patient underwent four meal tests with 40?g or 100?g of carbohydrates (CHOs), both on two occasions. For each meal, the iBolus or the traditional bolus (tBolus) was given before mealtime (t(0)) in a randomized order. We measured the postprandial glycemic response as the area under the curve of plasma glucose (AUC-PG(0-5h)) and variability as the individual coefficient of variation (CV) of AUC-PG(0-5h). The contribution of the insulin-to-CHO ratio, CHO, plasma glucose at t(0) (PG(t0)), and insulin dose to AUC-PG(0-5h) and its CV was also investigated.AUC-PG(0-5h) was similar with either bolus for 40-g (iBolus vs. tBolus, 585.5±127.5 vs. 689.2±180.7?mg/dL·h) or 100-g (752.1±237.7 vs. 760.0±263.2?mg/dL·h) CHO meals. A multiple regression analysis revealed a significant model only for the tBolus, with PG(t0) being the best predictor of AUC-PG(0-5h) explaining approximately 50% of the glycemic response. Observed variability was greater with the iBolus (CV, 16.7±15.3% vs. 10.1±12.5%) but independent of the factors studied.A CGM-based algorithm for calculation of prandial insulin is feasible, although it does not reduce unpredictability of individual glycemic responses. Causes of variability need to be identified and analyzed for further optimization of postprandial glycemic control.