Influence of Fasting until Noon (Extended Postabsorptive State) on Clock Gene mRNA Expression and Regulation of Body Weight and Glucose Metabolism.

The trend of fasting until noon (omission or delayed breakfast) is increasingly prevalent in modern society. This eating pattern triggers discordance between endogenous circadian clock rhythms and the feeding/fasting cycle and is associated with an increased incidence of obesity and T2D. Although the underlying mechanism of this association is not well understood, growing evidence suggests that fasting until noon, also known as an "extended postabsorptive state", has the potential to cause a deleterious effect on clock gene expression and to disrupt regulation of body weight, postprandial and overall glycemia, skeletal muscle protein synthesis, and appetite, and may also lead to lower energy expenditure. This manuscript overviews the clock gene-controlled glucose metabolism during the active and resting phases and the consequences of postponing until noon the transition from postabsorptive to fed state on glucose metabolism, weight control, and energy expenditure. Finally, we will discuss the metabolic advantages of shifting more energy, carbohydrates (CH), and proteins to the early hours of the day.

Serum from type 2 diabetes patients consuming a three-meal diet resets circadian rhythms in cultured hepatocytes.

AIMS: Feeding regimens alter circadian rhythms in peripheral tissues, but the mechanism is not understood. We aimed to study whether soluble factors, rather than neuronal-based communication, directly influence circadian rhythms in the liver, in response to a nutritional treatment in type 2 diabetes (T2D) patients. METHODS: Cultured hepatocytes were treated with serum of insulin-treated T2D patients following either a three-meal diet (3Mdiet) or six-meal diet (6Mdiet) and the circadian expression of clock and metabolic genes was measured. RESULTS: Serum of the 3Mdiet group led to increased amplitudes and daily mRNA levels of the positive limb of the circadian clock (Clock, Bmal1, Rorα). In parallel, serum of the 3Mdiet group led to the downregulation of the negative limb of the circadian clock (Cry1 and Per1), compared to both baseline and 6Mdiet. In contrast, serum of the 6Mdiet group led to a more distorted expression pattern. The catabolic genes Sirt1 and Ampk were significantly upregulated only by serum of the 3Mdiet group. CONCLUSIONS: Our results show that serum of type 2 diabetes patients consuming the 3Mdiet contains soluble factors that reset circadian rhythms leading to an expression pattern similar to that of healthy people. This clock pattern contributes to improved glucose metabolism.

Role of High Energy Breakfast "Big Breakfast Diet" in Clock Gene Regulation of Postprandial Hyperglycemia and Weight Loss in Type 2 Diabetes.

Postprandial hyperglycemia (PPHG) is strongly linked with the future development of cardiovascular complications in type 2 diabetes (T2D). Hence, reducing postprandial glycemic excursions is essential in T2D treatment to slow progressive deficiency of ß-cell function and prevent cardiovascular complications. Most of the metabolic processes involved in PPHG, i.e., ß-cell secretory function, GLP-1 secretion, insulin sensitivity, muscular glucose uptake, and hepatic glucose production, are controlled by the circadian clock and display daily oscillation. Consequently, postprandial glycemia displays diurnal variation with a higher glycemic response after meals with the same carbohydrate content, consumed at dusk compared to the morning. T2D and meal timing schedule not synchronized with the circadian clock (i.e., skipping breakfast) are associated with disrupted clock gene expression and is linked to PPHG. In contrast, greater intake in the morning (i.e., high energy breakfast) than in the evening has a resetting effect on clock gene oscillations and beneficial effects on weight loss, appetite, and reduction of PPHG, independently of total energy intake. Therefore, resetting clock gene expression through a diet intervention consisting of meal timing aligned to the circadian clock, i.e., shifting most calories and carbohydrates to the early hours of the day, is a promising therapeutic approach to improve PPHG in T2D. This review will focus on recent studies, showing how a high-energy breakfast diet (Bdiet) has resetting and synchronizing actions on circadian clock genes expression, improving glucose metabolism, postprandial glycemic excursions along with weight loss in T2D.

Reduction in Glycated Hemoglobin and Daily Insulin Dose Alongside Circadian Clock Upregulation in Patients With Type 2 Diabetes Consuming a Three-Meal Diet: A Randomized Clinical Trial.

OBJECTIVE: In type 2 diabetes, insulin resistance and progressive ß-cell failure require treatment with high insulin doses, leading to weight gain. Our aim was to study whether a three-meal diet (3Mdiet) with a carbohydrate-rich breakfast may upregulate clock gene expression and, as a result, allow dose reduction of insulin, leading to weight loss and better glycemic control compared with an isocaloric six-meal diet (6Mdiet). RESEARCH DESIGN AND METHODS: Twenty-eight volunteers with diabetes (BMI 32.4 ± 5.2 kg/m2 and HbA1c 8.1 ± 1.1% [64.5 ± 11.9 mmol/mol]) were randomly assigned to 3Mdiet or 6Mdiet. Body weight, glycemic control, continuous glucose monitoring (CGM), appetite, and clock gene expression were assessed at baseline, after 2 weeks, and after 12 weeks. RESULTS: 3Mdiet, but not 6Mdiet, led to a significant weight loss (-5.4 ± 0.9 kg) (P < 0.01) and decreased HbA1c (-12 mmol/mol [-1.2%]) (P < 0.0001) after 12 weeks. Fasting glucose and daily and nocturnal glucose levels were significantly lower on the 3Mdiet. CGM showed a significant decrease in the time spent in hyperglycemia only on the 3Mdiet. Total daily insulin dose was significantly reduced by 26 ± 7 units only on the 3Mdiet. There was a significant decrease in the hunger and cravings only in the 3Mdiet group. Clock genes exhibited oscillation, increased expression, and higher amplitude on the 3Mdiet compared with the 6Mdiet. CONCLUSIONS: A 3Mdiet, in contrast to an isocaloric 6Mdiet, leads to weight loss and significant reduction in HbA1c, appetite, and overall glycemia, with a decrease in daily insulin. Upregulation of clock genes seen in this diet intervention could contribute to the improved glucose metabolism.

Bariatric surgery in patients with type 1 diabetes: special considerations are warranted.

OBJECTIVE: We examined short and long-term outcomes of bariatric surgery in patients with obesity and type 1 diabetes mellitus (T1DM). METHODS: We reviewed the records of all adults insured by Maccabi Healthcare Services during 2010 -2015, with body mass index (BMI) ⩾30 kg/m2 and T1DM; and compared weight reduction and glucose control according to the performance of bariatric surgery. BMI and glycated hemoglobin (HbA1c) levels were extracted for baseline and every 6 months, for a mean 3.5 years. RESULTS: Of 52 patients, 26(50%) underwent bariatric surgery. Those who underwent surgery were more often female and with a longer duration of diabetes. Immediately postoperative, 4(15%) developed diabetic ketoacidosis, while 6(23%) experienced severe hypoglycemic episodes. The mean BMI decreased among surgery patients: from 39.5±4.4 to 30.1±5.0 kg/m2 (p < 0.0001); and increased among those who did not undergo surgery: from 33.6±3.9 to 35.1±4.4 kg/m2 (p = 0.49). The mean HbA1c level decreased during the first 6 months postoperative: from 8.5±0.9% to 7.9±0.9%; however, at the end of follow-up, was similar to baseline, 8.6±2.0% (p = 0.87). For patients who did not undergo surgery, the mean HbA1c increased from 7.9±1.9% to 8.6±1.5% (p = 0.09). CONCLUSIONS: Among individuals with obesity and T1DM, weight loss was successful after bariatric surgery, but glucose control did not improve. The postoperative risks of diabetic ketoacidosis and severe hypoglycemic episodes should be considering when performing bariatric surgery in this population.

Improved outcome of patients with diabetes mellitus with good glycemic control in the cardiac intensive care unit: a retrospective study.

BACKGROUND: Diabetes mellitus (DM) is a prevalent metabolic disease characterized by chronic hyperglycemia. A primary burden of DM is related to its long-term complications, which have been shown to impact the course of hospitalization and to influence patients' outcome. AIM: To assess the role of in-hospital glucose control on length of stay, 30-days and 1-year mortality. METHODS: This is a retrospective study that included patients admitted to the cardiac intensive care unit (CICU) of the Edith Wolfson Medical Centre between 01 January, 2010 and 31 December 2013. Blood glucose was measured by glucometer and fed into an interactive database. Glucose status was referred to as controlled when more than 50% of a given patients glucose values were between 71 and 200 mg/dL. Chisquared tests were used to assess the distribution of categorical variables, while the ttest was applied for continuous variables. A multivariate logistic regression model was used to analyze the association between glucose control and mortality. Cox regression was conducted to assess survival and 1-year mortality. RESULTS: 2466 patients were admitted to the CICU over the study period, of which 370 had concomitant diabetes mellitus. Controlled glucose status was associated with shorter length of hospital stay (1.6 ± 1.7 versus 2.6 ± 3.0, p < 0.001), reduced 30-day mortality (0.7% versus 4.6%, p < 0.001), and improved 1-year mortality (2.2% versus 7.5%, p < 0.001). Moreover, attainment of glucose control was independently associated with a significant decrease in 1-year mortality (OR = 0.371, 95% CI 0.140-0.988, p = 0.047). CONCLUSION: In-hospital control of glucose parameters is associated with shorter length of hospital stay, and lowered 30-day and 1-year mortality. An effort to maintain glucose levels within reference ranges is warranted in critically ill patients to reduce mortality.

Hypoglycemia- simplifying the ways to predict an old problem in the general ward.

OBJECTIVE: To examine the association between hypoglycemic events and inpatient and outpatient mortality rates, and to characterize the profile of patients with diabetes who develop hypoglycemia during hospitalization in order to identify risk factors and potentially avoid it. RESEARCH DESIGN AND METHODS: This retrospective cohort study analyzed data of 3410 patients with diabetes hospitalized during 2012. The associations among biochemical measures, severity of hypoglycemia, inpatient length of stay, and mortality during hospitalization, one month and within one year after discharge were evaluated. RESULTS: Hypoglycemia was observed in 18.5% (633/3410) of patients with diabetes, 83% (529/633) with mild/moderate hypoglycemic values. Adjusted for age and sex, the 30-day mortality rate after discharge was higher in the group with mild/moderate hypoglycemia (HR = 1.749, CI 1.288-2.374, p < 0.001) and in the group with severe hypoglycemia (HR = 3.390, CI 2.332-6.100, p < 0.001). The mortality rate at the one-year follow-up was higher in the group with mild/moderate hypoglycemia (HR = 1.749, CI 1.288-2.374, p < 0.001) and in the group with severe hypoglycemia (HR = 3.390, CI 2.332-6.100, p < 0.001). In multivariate analysis, hemoglobin and albumin below normal values, and creatinine values above the upper limit were strongly associated with hypoglycemia (OR 1.35, 95%CI 1.1-1.6, p < 0.03; OR 1.6, 95%CI 1.33-1.89, p < 0.001; OR 1.3, 95%CI 1.08-1.55, p < 0.04, respectively). CONCLUSIONS: Hospitalized patients with diabetes and low hemoglobin, low albumin or high creatinine levels are at increased risk of developing significant hypoglycemia. Identifying accurate high-risk factors in order to intervene early and efficiently can prevent life-threatening complications.

Lifestyle intervention program benefits children with overweigh compared to children with obesity.

BACKGROUND: Lifestyle weight loss interventions represent the mainstay of treating children with obesity. Long-term follow-up studies of intervention programs are scarce. This study assessed the long-term effects and identified factors associated with significant weight loss. METHODS: This prospective, observational study involved 165 children with body mass index (BMI) z-score ≥1.5 who participated in after-school intervention program. MAIN OUTCOME MEASURE: change in BMI z-scores; decreased BMI z-score ≥0.5 units was defined as clinically significant. RESULTS: At baseline, 55/165 (33.3%) had BMI z-score 1.5-2 and 98 (59.4%) had BMI z-score >2. At follow-up (mean 5.4±1.4 years), 80 (48.5%) had a clinically significant reduction in BMI z-score, while 56 (33.9%) reported a mildly decrease in BMI z-score of 0-0.5 and 29 (17.6%) reported increased BMI z-score. Lower BMI z-score at baseline and participation in sport activity at follow-up were associated with long-term decrease in BMI z-score. Participation in additional post-intervention weight control programs was correlated with weight gain. CONCLUSIONS: Intervention program was associated with long-term improvement in weight control, especially in children with mild obesity. Physical activity was related to long-term success. Participation in an additional intervention program was associated with failure of weight control.

High-energy breakfast based on whey protein reduces body weight, postprandial glycemia and HbA1C in Type 2 diabetes.

Acute studies show that addition of whey protein at breakfast has a glucose-lowering effect through increased incretin and insulin secretion. However, whether this is a long-term effect in Type 2 diabetes is unknown. Fifty-six Type 2 diabetes participants aged 58.9±4.5 years, BMI 32.1±0.9 kg/m2 and HbA1C 7.8±0.1% (61.6±0.79 mmol/mol) were randomized to one of 3 isocaloric diets with similar lunch and dinner, but different breakfast: 1) 42 g total protein, 28 g whey (WBdiet, n=19); 2) 42 g various protein sources (PBdiet, n=19); or 3) high-carbohydrate breakfast, 17 g protein from various sources (CBdiet, n=18). Body weight and HbA1C were examined after 12 weeks. All participants underwent three all-day meal challenges for postprandial glycemia, insulin, C-peptide, intact glucagon-like peptide 1 (iGLP-1), ghrelin and hunger and satiety scores. Overall postprandial AUCglucose was reduced by 12% in PBdiet and by 19% in WBdiet, compared with CBdiet (P<.0001). Compared with PBdiet and CBdiet, WBdiet led to a greater postprandial overall AUC for insulin, C-peptide, iGLP-1 and satiety scores, while postprandial overall AUC for ghrelin and hunger scores were reduced (P<.0001). After 12 weeks, HbA1C was reduced after WBdiet by 0.89±0.05% (11.5±0.6 mmol/mol), after PBdiet by 0.6±0.04% (7.1±0.31 mmol/mol) and after CBdiet by 0.36±0.04% (2.9±0.31 mmol/mol) (P<.0001). Furthermore, the participants on WBdiet lost 7.6±0.3 kg, PBdiet 6.1±0.3 kg and CBdiet 3.5±0.3 kg (P<.0001). Whey protein-based breakfast is an important adjuvant in the management of Type 2 diabetes.

Influences of Breakfast on Clock Gene Expression and Postprandial Glycemia in Healthy Individuals and Individuals With Diabetes: A Randomized Clinical Trial.

OBJECTIVE: The circadian clock regulates glucose metabolism by mediating the activity of metabolic enzymes, hormones, and transport systems. Breakfast skipping and night eating have been associated with high HbA1c and postprandial hyperglycemia after lunch and dinner. Our aim was to explore the acute effect of breakfast consumption or omission on glucose homeostasis and clock gene expression in healthy individuals and individuals with type 2 diabetes. RESEARCH DESIGN AND METHODS: In a crossover design, 18 healthy volunteers and 18 volunteers with 14.5 ± 1.5 years diabetes, BMI 30.7 ± 1.1 kg/m2, and HbA1c 7.6 ± 0.1% (59.6 ± 0.8 mmol/mol) were randomly assigned to a test day with breakfast and lunch (YesB) and a test day with only lunch (NoB). Postprandial clock and clock-controlled gene expression, plasma glucose, insulin, intact glucagon-like peptide 1 (iGLP-1), and dipeptidyl peptidase IV (DPP-IV) plasma activity were assessed after breakfast and lunch. RESULTS: In healthy individuals, the expression level of Per1, Cry1, Rorα, and Sirt1 was lower (P < 0.05) but Clock was higher (P < 0.05) after breakfast. In contrast, in individuals with type 2 diabetes, Per1, Per2, and Sirt1 only slightly, but significantly, decreased and Rorα increased (P < 0.05) after breakfast. In healthy individuals, the expression level of Bmal1, Rorα, and Sirt1 was higher (P < 0.05) after lunch on YesB day, whereas the other clock genes remained unchanged. In individuals with type 2 diabetes, Bmal1, Per1, Per2, Rev-erbα, and Ampk increased (P < 0.05) after lunch on the YesB day. Omission of breakfast altered clock and metabolic gene expression in both healthy and individuals with type 2 diabetes. CONCLUSIONS: Breakfast consumption acutely affects clock and clock-controlled gene expression leading to normal oscillation. Breakfast skipping adversely affects clock and clock-controlled gene expression and is correlated with increased postprandial glycemic response in both healthy individuals and individuals with diabetes.

Random blood glucose screening at a public health station encouraged high risk subjects to make lifestyle changes.

BACKGROUND: Screening and early diagnosis of prediabetes and diabetes can prevent or delay disease onset and complications. To that end, a free public health station was established in a large, government medical centre. This study evaluated the long-term outcomes of abnormal random blood glucose results among patients with no history of diabetes or prediabetes. METHODS: The Diabetes Unit supervised a public dysglycaemia and hypertension screening station. Participants with blood glucose >140 mg/dL and no history of diabetes or prediabetes were contacted by telephone for follow-up. RESULTS: Among screened subjects, 868 (average age 57.5±12 years) had a random blood glucose level >140 mg/dL and 341 (39.3%) responded to the telephone survey. Of these, 313 (91.8%) subsequently had fasting blood glucose measured at their health maintenance organisation (HMO), of which 101 (32.3%) were abnormal. A total of 173 (51%) respondents initiated interventions: 59 (17.3%) antidiabetic treatment; 145 (42.5%) sugar-restricted diet; and 96 (28.2%) a physical activity programme. Of patients with abnormal fasting blood glucose, 17 (14.5%) reported having had this result previously compared with 9 (4.2%) with normal fasting glucose (P=.001). Among respondents, 216 (63.3%) stated the screening was effective and 273 (80.1%) would recommend it. CONCLUSION: The station was effective in promoting additional screening among high-risk age groups and encourages subjects to make lifestyle changes. Operating the screening station is simple and effective; therefore it may serve as a complementary step in promoting community healthcare.

Prevalence of undiagnosed hyperglycaemia in patients presenting to the Department of Emergency Medicine with no known history of diabetes.

BACKGROUND: Diabetes is considered a major epidemic of the 21st century. Usually, diabetes begins asymptomatically and the diagnosis takes place an average of 8-12 years after the onset of dysglycaemia. Blood check for glucose is taken at different medical setting, whether at the fasting condition or randomly. Previous studies had shown that abnormal blood glucose predicts future diabetes. Hence, medical staff should consider taking reasonable actions in patients with abnormal blood glucose. OBJECTIVE: To assess the prevalence of hyperglycaemia in patients presenting to the Department of Emergency Medicine (DEM) with no known history of diabetes, and to evaluate how often were they recommended following this up as an outpatient by the medical staff. DESIGN: A cross-sectional study examined the medical records of adult patients referred to the DEM during 1 November 2011-31 January 2012. PARTICIPANTS: Patients with random blood glucose ≥140 mg/dL and no known history of diabetes were included in the study. The discharge letter was examined for the presence of instructions to conduct further follow up. KEY RESULTS: A total of 16 784 patients presented to the DEM. Of these, 402 patients (2.4%) without known diabetes were hyperglycaemic, 346 patients had blood glucose levels ≥140 mg/dL and 56 patients had blood glucose levels above 200 mg/dL. Only 35 of the 402 included patient files (8.7%) contained instructions for further investigation. There was no statistically significant difference between those who received a letter for further follow up compared with those who did not receive it with respect to age, sex or blood glucose levels. CONCLUSION: Over 2% of patients who presented to the DEM were hyperglycaemic, without a prior diagnosis of diabetes. A small per cent was recommended to have outpatient follow-up. This represents a missed opportunity for earlier diagnosis of diabetes and emphasised the need for raising medical staff awareness concerning abnormal blood glucose and its implication.

Pioglitazone Therapy Increases Insulin-Stimulated Release of d-Chiro-Inositol-Containing Inositolphosphoglycan Mediator in Women with Polycystic Ovary Syndrome.

BACKGROUND: Insulin resistance in women with polycystic ovary syndrome (PCOS) may be mediated, in part, by a deficiency in the insulin-stimulated release of a d-chiro-inositol-inositolphosphoglycan (DCI-IPG) mediator of insulin action. Supporting this idea, several studies have reported improved insulin sensitivity in both lean and obese women with PCOS after oral administration of DCI. Pioglitazone improves insulin sensitivity in women with PCOS, but it is unknown whether this may be contributed by enhanced insulin-stimulated release of the DCI-IPG second messenger. The study aimed to determine if pioglitazone increases release of biologically active DCI-IPG per unit insulin released during an oral glucose tolerance test (OGTT). METHODS: A randomized, double-blind placebo-controlled trial was conducted in 32 women with PCOS at a tertiary referral center in Venezuela. The intervention comprised administration of pioglitazone 45 mg daily or matched placebo for 6 months. Outcome measures included area under curves (AUC) of DCI-IPG (AUCDCI-IPG), insulin (AUCinsulin), and the ratio of AUCDCI-IPG to AUCinsulin during a 2-hr OGTT. RESULTS: After treatment with pioglitazone, AUCinsulin during the OGTT decreased and whole body insulin sensitivity, as determined by the Matsuda index, increased significantly only in the pioglitazone group. The ratio of AUCDCI-IPG/AUCinsulin increased in the pioglitazone group by 1.85-fold (P < 0.0001) with no significant change in the placebo group. Change in Matsuda index correlated with change in DCI-IPG released per unit of insulin during OGTT (r = 0.47, P < 0.01). CONCLUSION: In women with PCOS, pioglitazone increased insulin-stimulated release of the DCI-IPG second messenger of insulin action, which may contribute to its insulin-sensitizing effect in these women.

Using a public health station for screening of undiagnosed dysglycemia and hypertension.

AIM: Dysglycemia, diabetes and abnormal blood pressure screening can be conducted by trained volunteers and may identify unknown cases. The aim of the study was to examine the feasibility and effectiveness of operating a screening station in pubic setting supervised by diabetes unit. METHODS: A cross-sectional analysis of a program offering free screening services to non-hospitalized subjects. From 1.1.2011 through 31.12.2013 trained volunteers measured height, weight, blood glucose and blood pressure at the main entrance of the hospital. Subjects were asked whether they had diabetes or hypertension. Dysglycemia was defined as blood glucose 141-199mg/dL and probable newly-identified diabetes as ≥200mg/dL. RESULTS: 13,112 adults underwent screening. Among the screened individuals (age 55.3±14.9 years) 2215 (16.9%) reported diabetes and 3037 (23.2%) hypertension. Among subjects without known hypertension, 9.6% had blood pressure ≥140/90. Among the subjects without known diabetes, 5012 (46%) had glucose ≤110mg/dL, 2873 (26.4%) ≥126mg/dL, 1553 (14.3%) >140mg/dL and 170 (1.6%) ≥200mg/dL. Compared to subjects with blood glucose ≤140mg/dL, those with dysglycemia or diabetes were older (58.9±13.4 vs. 52.7±15.2 years, P<0.001), had elevated BMI (27.5±4.6kg/m(2) vs. 26.6±4.6kg/m(2), P<0.001), higher systolic (137.5±22.2mmHg vs. 132.2±21.3mmHg, P<0.001) and diastolic blood pressure (80.3±15.6mmHg vs. 78.6±13.7mmHg, P<0.001). Compared to subjects with blood glucose<200mg/dL, those with probable newly-identified diabetes were older (58.6±10.9 vs. 53.5±15.2, P<0.001), had elevated BMI (28.4±4.8kg/m(2) vs. 26.7±4.6kg/m(2), P<0.001), higher systolic (139.4±24.0mmHg vs. 132.8±21.4mmHg, P<0.001) and diastolic blood pressure (85.4±20.7mmHg vs. 78.8±13.9mmHg, P<0.001). CONCLUSIONS: Screening supervised by healthcare center can identify individuals at high-risk for dysglycemia and abnormal blood pressure, who are referred for further diagnosis and treatment and may serve as a complementary step in primary health care setting.

Purslane Extract and Glucose Homeostasis in Adults with Type 2 Diabetes: A Double-Blind, Placebo-Controlled Clinical Trial of Efficacy and Safety.

Purslane extract (PE) is derived from Portulaca oleracea L., a medicinal plant used in traditional medicine for its antidiabetic properties. This randomized, placebo-controlled clinical trial was designed to evaluate the efficacy and safety of PE in improving glucose control, blood pressure, and lipid profile in adults with type 2 diabetes mellitus (T2DM) treated with a single oral hypoglycemic agent at baseline. Subjects were randomized to treatment with three capsules of PE/day or a matched placebo. Change from baseline to the week 12 end-of-follow-up visit measures of glucose homeostasis, hemodynamics, and lipid profile was compared by treatment assignment. In addition, these measures were evaluated in a subgroup of "responders," defined as patients whose week 12 HbA1c was lower than baseline values, regardless of treatment assignment. This group was further assessed in subgroups of baseline oral hypoglycemic treatment. A total of 63 participants were treated with either PE (n = 31, 11 females, mean age 52.4 ± 7.9 years) or matched placebo (n = 32, 11 females, mean age 58.3 ± 10.8 years). In the total cohort, systolic blood pressure declined significantly more in the PE group than the placebo group: -7.5 ± 5.0 versus -0.01 ± 0.3 mmHg, P < .0001. In the responders' subgroup, HbA1c declined significantly more in the PE group than the placebo group: -0.8% ± 0.4% versus -0.6% ± 0.5%, P = .03. Few adverse events were reported. These were mild and did not differ by treatment assignment. PE appears to be a safe, adjunct treatment for T2DM, significantly reducing systolic blood pressure in the total cohort and HbA1c in the subgroup of responders.

Fasting until noon triggers increased postprandial hyperglycemia and impaired insulin response after lunch and dinner in individuals with type 2 diabetes: a randomized clinical trial.

OBJECTIVE: Skipping breakfast has been consistently associated with high HbA1c and postprandial hyperglycemia (PPHG) in patients with type 2 diabetes. Our aim was to explore the effect of skipping breakfast on glycemia after a subsequent isocaloric (700 kcal) lunch and dinner. RESEARCH DESIGN AND METHODS: In a crossover design, 22 patients with diabetes with a mean diabetes duration of 8.4 ± 0.7 years, age 56.9 ± 1.0 years, BMI 28.2 ± 0.6 kg/m(2), and HbA1c 7.7 ± 0.1% (61 ± 0.8 mmol/mol) were randomly assigned to two test days: one day with breakfast, lunch, and dinner (YesB) and another with lunch and dinner but no breakfast (NoB). Postprandial plasma glucose, insulin, C-peptide, free fatty acids (FFA), glucagon, and intact glucagon-like peptide-1 (iGLP-1) were assessed. RESULTS: Compared with YesB, lunch area under the curves for 0-180 min (AUC0-180) for plasma glucose, FFA, and glucagon were 36.8, 41.1, and 14.8% higher, respectively, whereas the AUC0-180 for insulin and iGLP-1 were 17% and 19% lower, respectively, on the NoB day (P < 0.0001). Similarly, dinner AUC0-180 for glucose, FFA, and glucagon were 26.6, 29.6, and 11.5% higher, respectively, and AUC0-180 for insulin and iGLP-1 were 7.9% and 16.5% lower on the NoB day compared with the YesB day (P < 0.0001). Furthermore, insulin peak was delayed 30 min after lunch and dinner on the NoB day compared with the YesB day. CONCLUSIONS: Skipping breakfast increases PPHG after lunch and dinner in association with lower iGLP-1 and impaired insulin response. This study shows a long-term influence of breakfast on glucose regulation that persists throughout the day. Breakfast consumption could be a successful strategy for reduction of PPHG in type 2 diabetes.

High-energy breakfast with low-energy dinner decreases overall daily hyperglycaemia in type 2 diabetic patients: a randomised clinical trial.

AIMS/HYPOTHESIS: High-energy breakfast and reduced-energy dinner (Bdiet) significantly reduces postprandial glycaemia in obese non-diabetic individuals. Our objective was to test whether this meal schedule reduces postprandial hyperglycaemia (PPHG) in patients with type 2 diabetes by enhancing incretin and insulin levels when compared with high-energy dinner and reduced-energy breakfast (Ddiet). METHODS: In a randomised, open label, crossover design performed in a clinic setting, 18 individuals (aged 30-70 years with BMI 22-35 kg/m(2)) with type 2 diabetes (<10 years duration) treated with metformin and/or diet were given either Bdiet or Ddiet for 7 days. Participants were randomised by a person not involved in the study using a coin flip. Postprandial levels of plasma glucose, insulin, C-peptide and intact and total glucagon-like peptide-1 (iGLP-1 and tGLP-1) were assessed. The Bdiet included 2,946 kJ breakfast, 2,523 kJ lunch and 858 kJ dinner. The Ddiet comprised 858 kJ breakfast, 2,523 kJ lunch and 2,946 kJ dinner. RESULTS: Twenty-two individuals were randomised and 18 analysed. The AUC for glucose (AUCglucose) throughout the day was 20% lower, whereas AUCinsulin, AUCC-peptide and AUCtGLP-1 were 20% higher for the Bdiet than the Ddiet. Glucose AUC0-180min and its peak were both lower by 24%, whereas insulin AUC0-180min was 11% higher after the Bdiet than the Ddiet. This was accompanied by 30% higher tGLP-1 and 16% higher iGLP-1 levels. Despite the diets being isoenergetic, lunch resulted in lower glucose (by 21-25%) and higher insulin (by 23%) with the Bdiet vs Ddiet. CONCLUSIONS/INTERPRETATION: High energy intake at breakfast is associated with significant reduction in overall PPHG in diabetic patients over the entire day. This dietary adjustment may have a therapeutic advantage for the achievement of optimal metabolic control and may have the potential for being preventive for cardiovascular and other complications of type 2 diabetes. Trial registration ClinicalTrials.gov NCT01977833 Funding No specific funding was received for the study.

Incretin, insulinotropic and glucose-lowering effects of whey protein pre-load in type 2 diabetes: a randomised clinical trial.

AIMS/HYPOTHESIS: Since protein ingestion is known to stimulate the secretion of glucagon-like peptide-1 (GLP-1), we hypothesised that enhancing GLP-1 secretion to harness its insulinotropic/beta cell-stimulating activity with whey protein pre-load may have beneficial glucose-lowering effects in type 2 diabetes. METHODS: In a randomised, open-label crossover clinical trial, we studied 15 individuals with well-controlled type 2 diabetes who were not taking any medications except for sulfonylurea or metformin. These participants consumed, on two separate days, 50 g whey in 250 ml water or placebo (250 ml water) followed by a standardised high-glycaemic-index breakfast in a hospital setting. Participants were randomised using a coin flip. The primary endpoints of the study were plasma concentrations of glucose, intact GLP-1 and insulin during the 30 min following meal ingestion. RESULTS: In each group, 15 patients were analysed. The results showed that over the whole 180 min post-meal period, glucose levels were reduced by 28% after whey pre-load with a uniform reduction during both early and late phases. Insulin and C-peptide responses were both significantly higher (by 105% and 43%, respectively) with whey pre-load. Notably, the early insulin response was 96% higher after whey. Similarly, both total GLP-1 (tGLP-1) and intact GLP-1 (iGLP-1) levels were significantly higher (by 141% and 298%, respectively) with whey pre-load. Dipeptidyl peptidase 4 plasma activity did not display any significant difference after breakfast between the groups. CONCLUSIONS/INTERPRETATION: In summary, consumption of whey protein shortly before a high-glycaemic-index breakfast increased the early prandial and late insulin secretion, augmented tGLP-1 and iGLP-1 responses and reduced postprandial glycaemia in type 2 diabetic patients. Whey protein may therefore represent a novel approach for enhancing glucose-lowering strategies in type 2 diabetes. Trial registration ClinicalTrials.gov NCT01571622 Funding The Israeli Ministry of Health and Milk Council funded the research.

Big breakfast rich in protein and fat improves glycemic control in type 2 diabetics.

OBJECTIVE: Our goal was to evaluate the effect of breakfast size and composition on body weight, glycemic control, and metabolic markers in adults with type 2 diabetes mellitus (T2DM). METHODS: 59 overweight/obese adults with T2DM were randomized to one of two isocaloric diabetic diets for 3 months; big breakfast (BB), breakfast was rich in fat and protein and provided 33% of total daily energy or small breakfast (SB), breakfast was rich in carbohydrates and provided 12.5% of total daily energy. RESULTS: Although body weight was reduced similarly in both groups, the BB group showed greater HbA1c and systolic blood pressure reductions (HbA1c: -4.62% vs. -1.46%, p = 0.047; SBP -9.58 vs. -2.43 mmHg; p = 0.04). T2DM medication dose was reduced in a greater proportion of the BB participants (31% vs. 0%; p = 0.002) while in the SB, a greater proportion of participants had a dose increases (16.7% vs. 3.4%; p = 0.002). Hunger scores were lower in the BB group and greater improvements in fasting glucose were observed in the BB group. CONCLUSIONS: A simple dietary manipulation enriching breakfast with energy as protein and fat appears to confer metabolic benefits and might be a useful alternative for the management of T2DM.

The use of a CoolSense device to lower pain sensation during finger pricking while measuring blood glucose in diabetes patients--a randomized placebo.

BACKGROUND: Patients with type 1 diabetes and a significant portion of patients with type 2 diabetes must use subcutaneous insulin injections, in order to maintain normoglycemia and to prevent immediate and long-term complications. For these patients, testing blood glucose levels more frequently is necessary to safely achieve glycated hemoglobin targets. In the current study, the effects of a CoolSense™ device (CoolSense Medical Ltd., Tel Aviv, Israel) were examined in relieving pain caused by needle-pricking for glucose measurements in adult patients with diabetes. SUBJECTS AND METHODS: One hundred seventy-seven patients assessed the severity of pain they experienced during needle-pricking. The patients were randomly divided into an experimental group or a control group that used either a cooled CoolSense instrument or a non-cooled device, respectively. Participants were asked to rank the severity of their pain by a questionnaire developed for this study. Blood glucose levels were monitored as a control. RESULTS: The majority of participants (58.3-71.7%; P<0.001) reported significant ache during measurements, the desire for an instrument that relieves pain, and its negative influence on their quality of life. Significant differences were indicated in pain perception between the experimental group and the control group that served as placebo, with no differences in blood glucose measurements in the groups. CONCLUSIONS: The CoolSense instrument significantly reduces subjective pain felt by patients and can therefore serve as an additional tool for clinicians to help ease the needle-pricking pain. Future study is needed in order to provide information regarding the practical use of the instrument and its effect on hyper- and hypoglycemia.