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Post hoc subgroup analysis of the HEART2D trial demonstrates lower cardiovascular risk in older patients targeting postprandial versus fasting/premeal glycemia.

ABSTRACT: To identify the Hyperglycemia and Its Effect After Acute Myocardial Infarction on Cardiovascular Outcomes in Patients With Type 2 Diabetes Mellitus (HEART2D) trial subgroups with treatment difference.In 1,115 type 2 diabetic patients who had suffered from an acute myocardial infarction (AMI), the HEART2D trial compared two insulin strategies targeting postprandial or fasting/premeal glycemia on time until first cardiovascular event (cardiovascular death, nonfatal MI, nonfatal stroke, coronary revascularization, or hospitalization for acute coronary syndrome). The HEART2D trial ended prematurely for futility. We used the classification and regression tree (CART) to identify baseline subgroups with potential treatment differences.CART estimated the age of >65.7 years to best predict the difference in time to first event. In the subgroup aged>65.7 years (prandial, n=189; basal, n=210), prandial patients had a significantly longer time to first event and a lower proportion experienced a first event (n=56 [29.6%] vs. n=85 [40.5%]; hazard ratio 0.69 [95% CI 0.49-0.96]; P=0.029), despite similar A1C levels.Older type 2 diabetic AMI survivors may have a lower risk for a subsequent cardiovascular event with insulin targeting postprandial versus fasting/premeal glycemia.

SUBMITTER: Raz I

PROVIDER: S-EPMC3120208 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature

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Post hoc subgroup analysis of the HEART2D trial demonstrates lower cardiovascular risk in older patients targeting postprandial versus fasting/premeal glycemia.

Raz Itamar I Ceriello Antonio A Wilson Peter W PW Battioui Chakib C Su Eric W EW Kerr Lisa L Jones Cate A CA Milicevic Zvonko Z Jacober Scott J SJ

Diabetes care 20110518 7

<h4>Objective</h4>To identify the Hyperglycemia and Its Effect After Acute Myocardial Infarction on Cardiovascular Outcomes in Patients With Type 2 Diabetes Mellitus (HEART2D) trial subgroups with treatment difference.<h4>Research design and methods</h4>In 1,115 type 2 diabetic patients who had suffered from an acute myocardial infarction (AMI), the HEART2D trial compared two insulin strategies targeting postprandial or fasting/premeal glycemia on time until first cardiovascular event (cardiovas ...[more]

PMID: 21593301

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Project description:IntroductionFew prospective clinical trials have investigated the role of fasting blood glucose (FBG) and/or postprandial glucose (PPG) in assessing overall glycemic control by using different insulin regimens. In the present post hoc analysis, we assessed the contribution of FBG and/or PPG in overall glycemic control in Chinese patients under insulin treatment.MethodsCLASSIFY is a phase IV, randomized, open-label, 26-week, parallel-arm, treat-to-target, multinational, controlled study in patients with type 2 diabetes mellitus to compare the efficacy and safety of insulin lispro mix 25 (LM25) and insulin lispro mix 50 (LM50) as starter insulins. Insulin was titrated with an aim to target pre-meal blood glucose (BG) levels at > 3.9 and ≤ 6.1 mmol/L before breakfast and dinner. The primary outcome assessed was the change in HbA1c from baseline.ResultsChinese patients contributed 38.7% (N = 156) of the total population. The majority of patients were male (52.6%). The mean (SD) body mass index was 24.54 (3.04) kg/m2 and mean (SD) HbA1c was 8.54 (1.10) % at baseline. At week 26, LM50 showed a significantly greater reduction from baseline in HbA1c (- 2.03% vs - 1.55%, P < 0.001), average daily BG (- 3.21 vs - 2.34 mmol/L, P < 0.001), average post-meal BG (- 3.58 vs - 2.39 mmol/L, P < 0.001), and average prandial BG excursion (- 1.01 vs - 0.22 mmol/L, P = 0.006) than the LM25 group. The reductions in average pre-meal BG (- 2.59 vs - 2.28 mmol/L, P = 0.137) were not significantly different between the groups. The proportion of patients achieving HbA1c targets (< 7% or ≤ 6.5%) without nocturnal hypoglycemia or weight gain was greater (P < 0.05) with LM50 compared with LM25.ConclusionLM50 achieved better overall glycemic control than LM25 as a starter insulin in Chinese patients, which may be due to greater improvement in PPG levels.Trial registrationClinicaltrials.gov identification number: NCT01773473.FundingEli Lilly and Company, Shanghai, China.

Project description:The optimal timing between meal ingestion and simple physical activity for improving blood glucose control is unknown. This study compared the effects of physical activity on postprandial interstitial glucose responses when the activity was conducted either immediately before, immediately after, or 30 min after breakfast. Forty-eight adults were randomized to three separate physical activity interventions: standing still (for 30 min), walking (for 30 min), and bodyweight exercises (3 sets of 10 squats, 10 push-ups, 10 lunges, 10 sit-ups). In each intervention, 16 participants completed four trials (A to D) during which a 500 kcal mixed nutrient liquid breakfast meal was consumed. Interstitial glucose responses were recorded using continuous glucose monitoring for 2 h after the meal. The activity was completed either after the glucose monitoring period (trial A; control) or immediately before (trial B), immediately after (trial C), or 30 min after (trial D) the breakfast. Mean, coefficient of variance (CV), and area under the curve (AUC) for glucose were calculated and compared between the four trials. Walking and bodyweight exercises immediately after the meal improved mean, CV, and AUC glucose (P ≤ 0.05 vs. control), while standing immediately after the meal only improved AUC glucose (P ≤ 0.05 vs. control) and nearly improved mean glucose (P = 0.06). Mean, CV, and AUC glucose were not affected by standing, walking, or bodyweight exercise conducted immediately before, or 30 min after the meal (all P > 0.05 vs. control). Energy intake (diet records) and energy expenditure (Actigraph) were consistent throughout the studies and did not influence the findings. Low- to moderate-intensity activity should be implemented soon after eating to improve glucose control following breakfast. The type of activity appears less important than the timing. These findings will help optimize exercise-meal timing in general health guidelines. ClinicalTrials.gov Identifier: NCT03730727.

Project description:BackgroundMetabolic flexibility is the responsiveness to heterogeneous physiological conditions, such as food ingestion. A key unresolved question is how inflammation affects metabolic flexibility.ObjectivesOur study objective was to compare metabolic flexibility, specifically the metabolomic response to a standardized meal, by fasting inflammation status.MethodsParticipants in Guatemala (n = 302, median age 44 y, 43.7% men) received a standardized, mixed-macronutrient liquid meal. Plasma samples (fasting, 2 h postmeal) were assayed by dual-column LC [reverse phase (C18) and hydrophilic interaction LC (HILIC)] with ultra-high-resolution MS, for concentrations of 6 inflammation biomarkers: high-sensitivity C-reactive protein (hsCRP), leptin, resistin, IL-10, adiponectin, and soluble TNF receptor II (TNFsR). We summed the individual inflammation biomarker z-scores, after reverse-coding of anti-inflammation biomarkers. We identified features with peak areas that differed between fasting and postmeal (false discovery rate-adjusted q <0.05) and compared median log2 postprandial/fasting peak area ratios by inflammation indicators.ResultsWe found 1397 C18 and 974 HILIC features with significant postprandial/fasting feature ratios (q <0.05). Overall inflammation z-score was directly associated with the postprandial/fasting feature ratios of arachidic acid, and inversely associated with the feature ratio of lysophosphatidic acid (LPA), adjusting for age and sex (all P < 0.05). The postprandial/fasting ratio of arachidic acid was negatively correlated with resistin, IL-10, adiponectin, and TNFsR concentrations (all P < 0.05). Feature ratios of several fatty acids-myristic acid [m/z 227.2018, retention time (RT) 229], heptadecanoic acid (m/z 269.2491, RT 276), linoleic acid (m/z 280.2358, RT 236)-were negatively correlated with fasting plasma concentrations of leptin (nanograms per milliliter) and adiponectin (micrograms per milliliter), respectively (all P < 0.05). The postprandial/fasting ratio of LPA was positively correlated with IL-10 and adiponectin (both P < 0.05); and the ratio of phosphatidylinositol was positively correlated with hsCRP (P < 0.05).ConclusionsPostprandial responses of fatty acids and glycerophospholipids are associated with fasting inflammation status in adults in Guatemala.

Project description:Background/objectivesTo investigate the effect of dried fruit in modifying postprandial glycemia, we assessed the ability of 4 dried fruits (dates, apricots, raisins, sultanas) to decrease postprandial glycemia through three mechanisms: a glycemic index (GI) effect, displacement effect, or 'catalytic' fructose effect.Subjects/methodsWe conducted an acute randomized, multiple-crossover trial in an outpatient setting in 10 healthy adults. Participants received 3 white bread control meals and 12 dried fruit test meals in random order. The test meals included each of 4 dried fruits (dates, apricots, raisins, sultanas) alone (GI effect), 4 of the dried fruits displacing half the available carbohydrate in white bread (displacement effect), or 4 of the dried fruits providing a small 'catalytic' dose (7.5 g) of fructose added to white bread ('catalytic' fructose effect). The protocol followed the ISO method for the determination of GI (ISO 26642:2010). The primary outcome was mean ± SEM GI (glucose scale) for ease of comparison across the three mechanisms.ResultsTen healthy participants (7 men, 3 women; mean ± SD age and BMI: 39 ± 12 years and 25 ± 2 kg/m2) were recruited and completed the trial. All dried fruit had a GI below that of white bread (GI = 71); however, only dried apricots (GI = 42 ± 5), raisins (GI = 55 ± 5), and sultanas (51 ± 4) showed a significant GI effect (P < 0.05). When displacing half the available carbohydrate in white bread, all dried fruit lowered the GI; however, only dried apricots (GI = 57 ± 5) showed a significant displacement effect (P = 0.025). None of the dried fruits showed a beneficial 'catalytic' fructose effect.ConclusionsIn conclusion, dried fruits have a lower GI and reduce the glycemic response of white bread through displacement of half of the available carbohydrate. Longer-term randomized trials are needed to confirm whether dried fruit can contribute to sustainable improvements in glycemic control.Trial registrationClinicalTrials.gov identifier, NCT02960373.

Project description:IntroductionIn our previous study investigating effects of luseogliflozin, a sodium-glucose cotransporter 2 inhibitor, on 24-h glycemic variability by continuous glucose monitoring (CGM), luseogliflozin elicited parallel downward shifts in fasting and postprandial glucose levels. However, further review of individual patients' data revealed that postprandial hyperglycemia was not reduced in some patients, while preprandial glucose was ameliorated in most patients. Therefore, we divided patients into two groups according to their postprandial glucose responses and conducted a post hoc subanalyses to elucidate which factors contributed to the differential effects of luseogliflozin.MethodsThirty-four Japanese type 2 diabetic patients in our previous randomized, double-blind, placebo-controlled, crossover study with 7-day luseogliflozin administration were divided into postprandial glucose responders (PGR, n = 23, ameliorated peak glucose) and postprandial glucose non-responders (PGNR; n = 11, non-ameliorated peak glucose). Baseline characteristics, variations in CGM-measured 24-h glucose levels, and other pharmacodynamic variabilities were compared.ResultsBaseline characteristics did not differ significantly between groups. Placebo-subtracted peak glucose was significantly lowered in PGR and significantly increased in PGNR (-43.8 and 17.9 mg/dL; both p < 0.05). Luseogliflozin significantly lowered "lowest glucose" (defined as the lowest level measured throughout a 24-h period) similarly in PGR and PGNR (-19.2 and -24.0 mg/dL; both p < 0.05), significantly reduced the mean amplitude of glucose excursions in PGR (-15.50 mg/dL; p < 0.05), and increased the area under the curve for plasma glucagon over 24 h in PGNR (median difference vs. placebo: 240 pg/mL h; p < 0.05). Luseogliflozin increased urinary glucose excretion (UGE) and decreased serum insulin by similar magnitudes in both groups.ConclusionsLuseogliflozin diminished glucose fluctuations in most patients by lowering peak glucose to a greater extent than lowest glucose. Luseogliflozin may also lower lowest glucose in patients whose peak glucose was not ameliorated despite increasing UGE. The glucagon increase in PGNR might explain its hypoglycemic effect on postprandial glucose.FundingTaisho Pharmaceutical Co., Ltd, Tokyo, Japan.Trial registrationJapicCTI-142548.

Project description:Global prevalence of type 2 diabetes (T2D) is rising and may affect 700 million people by 2045. Totum-63 is a polyphenol-rich natural composition developed to reduce the risk of T2D. We first investigated the effects of Totum-63 supplementation in high-fat diet (HFD)-fed mice for up to 16 wk and thereafter assessed its safety and efficacy (2.5 g or 5 g per day) in 14 overweight men [mean age 51.5 yr, body mass index (BMI) 27.6 kg·m-2] for 4 wk. In HFD-fed mice, Totum-63 reduced body weight and fat mass gain, whereas lean mass was unchanged. Moreover, fecal energy excretion was higher in Totum-63-supplemented mice, suggesting a reduction of calorie absorption in the digestive tract. In the gut, metagenomic analyses of fecal microbiota revealed a partial restoration of HFD-induced microbial imbalance, as shown by principal coordinate analysis of microbiota composition. HFD-induced increase in HOMA-IR score was delayed in supplemented mice, and insulin response to an oral glucose tolerance test was significantly reduced, suggesting that Totum-63 may prevent HFD-related impairments in glucose homeostasis. Interestingly, these improvements could be linked to restored insulin signaling in subcutaneous adipose tissue and soleus muscle. In the liver, HFD-induced steatosis was reduced by 40% (as shown by triglyceride content). In the subsequent study in men, Totum-63 (5 g·day-1) improved glucose and insulin responses to a high-carbohydrate breakfast test (84% kcal carbohydrates). It was well tolerated, with no clinically significant adverse events reported. Collectively, these data suggest that Totum-63 could improve glucose homeostasis in both HFD-fed mice and overweight individuals, presumably through a multitargeted action on different metabolic organs.NEW & NOTEWORTHY Totum-63 is a novel polyphenol-rich natural composition developed to reduce the risk of T2D. Totum-63 showed beneficial effects on glucose homeostasis in HFD-fed mice, presumably through a multitargeted action on different metabolic organs. Totum-63 was well tolerated in humans and improved postprandial glucose and insulin responses to a high-carbohydrate breakfast test.

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Post hoc subgroup analysis of the HEART2D trial demonstrates lower cardiovascular risk in older patients targeting postprandial versus fasting/premeal glycemia.

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Post hoc subgroup analysis of the HEART2D trial demonstrates lower cardiovascular risk in older patients targeting postprandial versus fasting/premeal glycemia.

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