Comparison of the effects of three insulinotropic drugs on plasma insulin levels after a standard meal

WSTĘP. Porównanie działania repaglinidu, glipizydu i glibenklamidu na wydzielanie insuliny i glukozy po posiłku próbnym zawierającym 500 kcal. MATERIAŁ I METODY. Do krzyżowej, randomizowanej, podwójnie ślepej próby zakwalifikowano 12 pacjentów z wczesną cukrzycą typu 2 (średnia wartość HbA1c 6,1%) oraz 12 osób jako grupę kontrolną. Chorzy losowo otrzymali placebo, 2 mg repaglinidu, 5 mg glipizydu i 5 mg glibenklamidu. Leki podawano po wzorcowym posiłku próbnym, zawierającym 500 kcal. Badania kolejnych leków wykonywano po okresie wydalania poprzedniego z organizmu (7–12 dni). WYNIKI. Wszystkie trzy leki miały jednakowy wpływ na całkowite posiłkowe wydzielanie insuliny (pole pod krzywą [AUC, area under the curve] -15-240 min). Zauważono jednak wyraźne różnice we wczesnym wydzielaniu insuliny (AUC -15-30 min): u badanych bez cukrzycy zarówno repaglinid, jak i glipizyd zwiększały wydzielanie insuliny odpowiednio o około 61 i 34% w porównaniu z placebo. Wśród chorych na cukrzycę różnica ta wynosiła odpowiednio 37 i 47%. W obu grupach stwierdzono istotną różnicę między glipizydem a glibenklamidem, natomiast repaglinid był skuteczniejszy niż glibenklamid tylko wśród zdrowych pacjentów bez cukrzycy. Wszystkie leki skutecznie obniżały całkowite stężenie glukozy AUC u chorych na cukrzycę i bez niej. Jednak wśród badanych bez cukrzycy repaglinid okazał się znamiennie skuteczniejszy niż glibenklamid. Różnicy takiej nie stwierdzono u chorych na cukrzycę, prawdopodobnie ze względu na częstsze występowanie insulinooporności w tej grupie. WNIOSKI. Repaglinid i glipizyd, ale nie glibenklamid, znacząco poprawiły wczesne wydzielanie insuliny po standardowym posiłku, zarówno wśród badanych bez cukrzycy, jak i wśród chorych na cukrzycę z zachowaną funkcją komórek b trzustki.INTRODUCTION. To compare the effects of repaglinide, glipizide, and glibenclamide on insulin secretion and postprandial glucose after a single standard 500-kcal test meal. MATERIAL AND METHODS. A total of 12 type 2 diabetic patients with early diabetes (mean HbA1c of 6.1%) and 12 matched control subjects were enrolled in this randomized, double-blind, crossover trial. Subjects received placebo, 2 mg repaglinide, 5 mg glipizide, and 5 mg glibenclamide in a random fashion during the trial. Administration of each drug was followed by a single standard 500-kcal test meal. A washout period of 7–12 days existed between the four study visits. RESULTS. All three drugs were equally effective on the total prandial insulin secretion (area under the curve [AUC] –15 to 240 min). However, clear differences were noted in the early insulin secretion (AUC –15 to 30 min); both repaglinide and glipizide increased secretion in nondiabetic subjects by ~61 and 34%, respectively, compared with placebo. In the diabetic patients, the difference versus placebo was 37 and 47%, respectively. The difference between glipizide and glibenclamide reached significance in both groups of subjects, whereas repaglinide was more effective than glibenclamide only in the healthy nondiabetic subject group. All three drugs were effective in decreasing total glucose AUC in the nondiabetic and diabetic population. In the nondiabetic subjects, however, repaglinide was significantly more effective than glibenclamide. The differences disappeared in the diabetic subjects, probably as a result of increased prevalence of insulin resistance in this group. CONCLUSIONS. Repaglinide and glipizide but not glibenclamide significantly enhanced the early insulin secretion in both nondiabetic and diabetic subjects with preserved b-cell function after a single standard meal

The Effects of Fructose Intake on Serum Uric Acid Vary among Controlled Dietary Trials1234

Hyperuricemia is linked to gout and features of metabolic syndrome. There is concern that dietary fructose may increase uric acid concentrations. To assess the effects of fructose on serum uric acid concentrations in people with and without diabetes, we conducted a systematic review and meta-analysis of controlled feeding trials. We searched MEDLINE, EMBASE, and the Cochrane Library for relevant trials (through August 19, 2011). Analyses included all controlled feeding trials ≥7 d investigating the effect of fructose feeding on uric acid under isocaloric conditions, where fructose was isocalorically exchanged with other carbohydrate, or hypercaloric conditions, and where a control diet was supplemented with excess energy from fructose. Data were aggregated by the generic inverse variance method using random effects models and expressed as mean difference (MD) with 95% CI. Heterogeneity was assessed by the Q statistic and quantified by I2. A total of 21 trials in 425 participants met the eligibility criteria. Isocaloric exchange of fructose for other carbohydrate did not affect serum uric acid in diabetic and nondiabetic participants [MD = 0.56 μmol/L (95% CI: −6.62, 7.74)], with no evidence of inter-study heterogeneity. Hypercaloric supplementation of control diets with fructose (+35% excess energy) at extreme doses (213–219 g/d) significantly increased serum uric acid compared with the control diets alone in nondiabetic participants [MD = 31.0 mmol/L (95% CI: 15.4, 46.5)] with no evidence of heterogeneity. Confounding from excess energy cannot be ruled out in the hypercaloric trials. These analyses do not support a uric acid-increasing effect of isocaloric fructose intake in nondiabetic and diabetic participants. Hypercaloric fructose intake may, however, increase uric acid concentrations. The effect of the interaction of energy and fructose remains unclear. Larger, well-designed trials of fructose feeding at “real world” doses are needed

Effect of Tree Nuts on Glycemic Control in Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Dietary Trials

<div><p>Background</p><p>Tree nut consumption has been associated with reduced diabetes risk, however, results from randomized trials on glycemic control have been inconsistent.</p><p>Objective</p><p>To provide better evidence for diabetes guidelines development, we conducted a systematic review and meta-analysis of randomized controlled trials to assess the effects of tree nuts on markers of glycemic control in individuals with diabetes.</p><p>Data Sources</p><p>MEDLINE, EMBASE, CINAHL, and Cochrane databases through 6 April 2014.</p><p>Study Selection</p><p>Randomized controlled trials ≥3 weeks conducted in individuals with diabetes that compare the effect of diets emphasizing tree nuts to isocaloric diets without tree nuts on HbA1c, fasting glucose, fasting insulin, and HOMA-IR.</p><p>Data Extraction and Synthesis</p><p>Two independent reviewer’s extracted relevant data and assessed study quality and risk of bias. Data were pooled by the generic inverse variance method and expressed as mean differences (MD) with 95% CI’s. Heterogeneity was assessed (Cochran Q-statistic) and quantified (I²).</p><p>Results</p><p>Twelve trials (n = 450) were included. Diets emphasizing tree nuts at a median dose of 56 g/d significantly lowered HbA1c (MD = −0.07% [95% CI:−0.10, −0.03%]; P = 0.0003) and fasting glucose (MD = −0.15 mmol/L [95% CI: −0.27, −0.02 mmol/L]; P = 0.03) compared with control diets. No significant treatment effects were observed for fasting insulin and HOMA-IR, however the direction of effect favoured tree nuts.</p><p>Limitations</p><p>Majority of trials were of short duration and poor quality.</p><p>Conclusions</p><p>Pooled analyses show that tree nuts improve glycemic control in individuals with type 2 diabetes, supporting their inclusion in a healthy diet. Owing to the uncertainties in our analyses there is a need for longer, higher quality trials with a focus on using nuts to displace high-glycemic index carbohydrates.</p><p>Trial Registration</p><p>ClinicalTrials.gov <a href="https://clinicaltrials.gov/ct2/show/NCT01630980?term=NCT01630980&rank=1" target="_blank">NCT01630980 </a></p></div

Fructose intake and cardiovascular risk factors in youth with type 1 diabetes: SEARCH for diabetes in youth study

AIMS: High consumption of dietary fructose has been shown to contribute to dyslipidemia and elevated blood pressure in adults, but there are few data in youth, particularly those at greater risk of cardiovascular disease (CVD). The aim of this study was to examine the association between fructose intake and CVD risk factors in a diverse population of youth with type 1diabetes (T1D). METHODS: This was a cross-sectional analysis of data from the SEARCH for Diabetes in Youth study, including 2085 youth ages 10–22 years with T1D, of which 22% were racial/ethnic minority and 50% were female. A semi-quantitative food frequency questionnaire was used to assess intake. RESULTS: Median daily fructose consumption was 7.9% of total calories. Fructose intake was positively associated with triglycerides (p<.01), but not with total cholesterol, LDL-cholesterol, HDL-cholesterol, or blood pressure after adjustment for physical activity and socio-demographic, clinical, and dietary covariates. An increase in fructose intake of 22 grams (equivalent to a 12 oz. can of soda) was associated with a 23% higher odds of borderline/ high versus low triglycerides (p<.005). CONCLUSION: These data suggest that children with T1D should moderate their intake of fructose, particularly those with borderline or high triglycerides

Forest plots of randomized controlled trials investigating the effect of diets supplemented with tree nuts on HOMA-IR in individuals with type 2 diabetes.

<p>Pooled effect estimate (<i>diamond</i>) for homeostasis model assessment of insulin resistance (HOMA-IR). Data are expressed as weighted mean differences (MD) with 95% CIs, using the generic inverse-variance fixed-effects model. Paired analyses were applied to all crossover trials. Inter-study heterogeneity was tested by the Cochran Q-statistic and quantified by I² at a significance level of P<0.10. n = number of participants in each treatment group.</p

Trial Characteristics,

<p>BMI = body mass index; C = crossover; CHO = carbohydrate; E = energy; HF = high fat; HOMA-IR = homeostasis model assessment of insulin resistance; IP = inpatient; LF = low fat; M = men; Met = metabolic feeding control; MQS = Heyland Methodological Quality Score; N/A = not available; NCEP = National Cholesterol Education Program; O = obese and overweight; OP = outpatient; P = parallel; SD = standard deviation; Supp = supplement feeding control; T2D = type 2 diabetes; W = women; wk = week; y = years.</p><p>*The number of participants listed for each trial in this column is the number of participants that completed the trial and therefore the number used in our analyses. The baseline characteristics reported by these trials were based on the number of participants listed here with the exception of 3 trials, Tapsell et al. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0103376#pone.0103376-Tapsell1" target="_blank">[36]</a>, Ma et al. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0103376#pone.0103376-Ma1" target="_blank">[35]</a>, and Darvish Damavandi et al. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0103376#pone.0103376-DamavandiRD1" target="_blank">[38]</a> where the values for mean age and/or mean body weight or BMI were derived from the number of participants present at baseline, a number that was different from the number of participants that completed the trial due to a per-protocol with drop-outs analysis. The number of participants present at baseline for these trials are as follows: Tapsell et al. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0103376#pone.0103376-Tapsell1" target="_blank">[36]</a>, n = 50; Ma et al. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0103376#pone.0103376-Ma1" target="_blank">[35]</a>, n = 24; Darvish Damavandi et al. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0103376#pone.0103376-DamavandiRD1" target="_blank">[38]</a>, n = 50; Sauder et al. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0103376#pone.0103376-Sauder1" target="_blank">[29]</a>, n = 30.</p>†<p>Baseline body weight or weight (kg) while receiving the control treatment in cross over trials, and baseline body weight in each treatment group in parallel trials. Baseline BMI values (kg/m²) are only reported when no data on weight were available.</p>‡<p>Countries are abbreviated using three letter country codes (ISO 3166-1 alpha-3 codes).</p>§<p>Metabolic feeding control (Met) was the provision of all meals, snacks, and study supplements (tree nuts) consumed during the study under controlled conditions. Supplement feeding control (Supp) was the provision of study supplements only.</p><p>|| Doses and % E (energy) preceded by “∼” represent values calculated on the basis of average reported energy intake of participants and average reported energy values of tree nuts from the USDA National Nutrient Database <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0103376#pone.0103376-US3" target="_blank">[59]</a>.</p>¶<p>All nut types were provided in whole form with the exception of 2 trials: Lovejoy et al. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0103376#pone.0103376-Lovejoy1" target="_blank">[27]</a> and Li et al. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0103376#pone.0103376-Li1" target="_blank">[34]</a>, which incorporated tree nuts into various entrées and snack foods (i.e. muffins, trail mixes, deserts, etc.).</p><p>**Comparators refers to 1) reference food(s) energy matched in exchange for tree nuts or 2) isocaloric control diet similar to the intervention diet but without tree nuts.</p>††<p>Planned energy from Carbohydrate:Protein:Fat. Measured energy end values from carbohydrate, protein, and fat are reported only if the study did not state the planned energy of prescribed diets.</p>‡‡<p>Trials with a MQS score ≥8 were considered to be of higher quality.</p>§§<p>Agency funding is that from government, university, or not-for-profit health agency sources. None of the trialists declared any conflicts of interest with the exception of Jenkins et al. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0103376#pone.0103376-Jenkins1" target="_blank">[33]</a> and Darvish Damavandi et al. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0103376#pone.0103376-DarvishDamavandiR1" target="_blank">[32]</a>.</p><p>|||| In this study participants randomized into the almond group were instructed to consume this dose 5 days/week.</p>¶¶<p>Mixed nuts included almonds, cashews, hazelnuts, macadamia nuts, peanuts, pecans, pistachios, walnuts.</p><p>***43% of the participants were obese and wished to lose weight; although this was not a weight loss study, they were given advice on portion size and fat intake to help them meet their weight-reduction objective.</p>†††<p>Data for this study was limited since the study’s conferences abstract and correspondence with the authors were the only sources of available data.</p

Forest plot of randomized controlled trials investigating the effect of diets supplemented with tree nuts on fasting insulin in individuals with type 2 diabetes.

<p>Pooled effect estimate (<i>diamond</i>) for fasting insulin (pmol/L). Data are expressed as weighted mean differences (MD) with 95% CIs, using the generic inverse-variance random-effects model. Paired analyses were applied to all crossover trials. Inter-study heterogeneity was tested by the Cochran Q-statistic and quantified by I² at a significance level of P<0.10. n = number of participants in each treatment group.</p

Forest plot of randomized controlled trials investigating the effect of diets supplemented with tree nuts on HbA1c in individuals with type 2 diabetes.

<p>Pooled effect estimate (<i>diamond</i>) for HbA1c (%). Data are expressed as weighted mean differences (MD) with 95% CIs, using the generic inverse-variance fixed effects model. Paired analyses were applied to all crossover trials. Inter-study heterogeneity was tested by the Cochran Q-statistic and quantified by I² at a significance level of P<0.10. n = number of participants in each treatment group.</p

Flow of the literature.

<p>Summary of search and selection process consists of the number of studies initially identified through database and manual search, excluded based on title and abstract, reviewed in full, excluded after full review, and final number of trials included in the meta-analysis.</p