Ralph J. F. Manders

Low-Intensity Exercise Reduces the Prevalence of Hyperglycemia in Type 2 Diabetes

INTRODUCTION Glycemic instability is a severely underestimated problem in type 2 diabetes treatment. Therapeutic targets should aim to reduce postprandial blood glucose excursions. Exercise prescription can effectively improve glucose homeostasis and reduce the risk of cardiovascular complications. AIM To assess the impact of a single, isoenergetic bout of low- (LI) and high-intensity (HI) exercise on the prevalence of hyperglycemia throughout the subsequent 24-h postexercise period in longstanding type 2 diabetes patients. METHODS Nine sedentary, male type 2 diabetes patients (age = 57 +/- 2 yr, body mass index = 29.0 +/- 1.0 kg x m(-2), Wmax = 2.2 +/- 0.2 W x kg(-1) body weight) were selected to participate in a randomized crossover study. Subjects performed an isoenergetic bout of endurance-type exercise for 60 min at 35% Wmax (LI) or 30 min at 70% Wmax (HI) or no exercise at all (NE). Thereafter, glycemic control was assessed during the subsequent 24-h postexercise period by continuous glucose monitoring under strict dietary standardization but otherwise free-living conditions. RESULTS Average 24-h glucose concentrations were reduced after the LI exercise bout (7.8 +/- 0.9 mmol x L(-1)) when compared with the control experiment (9.4 +/- 0.8 mmol x L(-1); P < 0.05). The HI exercise bout did not significantly lower mean glucose concentrations (8.7 +/- 0.7 mmol x L(-1); P = 0.14). Hyperglycemia was prevalent for as much as 35% +/- 9% throughout the day (NE). A single bout of exercise reduced the prevalence of hyperglycemia by 50% +/- 4% (P < 0.05) and 19% +/- 9% (P = 0.13) in the LI and HI exercise experiments, respectively. CONCLUSIONS A single bout of LI, as opposed to HI, exercise substantially reduces the prevalence of hyperglycemia throughout the subsequent 24-h postexercise period in longstanding type 2 diabetes patients.

Effects of high-intensity interval exercise versus continuous moderate-intensity exercise on postprandial glycemic control assessed by continuous glucose monitoring in obese adults

The purpose of this study was to examine the impact of acute high-intensity interval training (HIIT) compared with continuous moderate-intensity (CMI) exercise on postprandial hyperglycemia in overweight or obese adults. Ten inactive, overweight or obese adults (41 ± 11 yrs, BMI = 36 ± 7 kg/m(2)) performed an acute bout of HIIT (10 × 1 min at approximately 90% peak heart rate (HRpeak) with 1-min recovery periods) or matched work CMI (30 min at approximately 65% HRpeak) in a randomized, counterbalanced fashion. Exercise was performed 2 h after breakfast, and glucose control was assessed by continuous glucose monitoring under standardized dietary conditions over 24 h. Postprandial glucose (PPG) responses to lunch, dinner, and the following days breakfast were analyzed and compared with a no-exercise control day. Exercise did not affect the PPG responses to lunch, but performing both HIIT and CMI in the morning significantly reduced the PPG incremental area under the curve (AUC) following dinner when compared with control (HIIT = 110 ± 35, CMI = 125 ± 34, control = 162 ± 46 mmol/L × 2 h, p < 0.05). The PPG AUC (HIIT = 125 ± 53, CMI = 186 ± 55, control = 194 ± 96 mmol/L × 2 h) and the PPG spike (HIIT = Δ2.1 ± 0.9, CMI = Δ3.0 ± 0.9, control = Δ3.0 ± 1.5 mmol/l) following breakfast on the following day were significantly lower following HIIT compared with both CMI and control (p < 0.05). Absolute AUC and absolute glucose spikes were not different between HIIT, CMI, or control for any meal (p > 0.05 for all). We conclude that a single session of HIIT has greater and more lasting effects on reducing incremental PPG when compared with CMI.

Glycaemic instability is an underestimated problem in Type II diabetes

The aim of the present study was to assess the level of glycaemic control by the measurement of 24 h blood glucose profiles and standard blood analyses under identical nutritional and physical activity conditions in patients with Type II diabetes and healthy normoglycaemic controls. A total of 11 male patients with Type II diabetes and 11 healthy matched controls participated in a 24 h CGMS (continuous subcutaneous glucose-monitoring system) assessment trial under strictly standardized dietary and physical activity conditions. In addition, fasting plasma glucose, insulin and HbA(1c) (glycated haemoglobin) concentrations were measured, and an OGTT (oral glucose tolerance test) was performed to calculate indices of whole-body insulin sensitivity, oral glucose tolerance and/or glycaemic control. In the healthy control group, hyperglycaemia (blood glucose concentration >10 mmol/l) was hardly present (2+/-1% or 0.4+/-0.2/24 h). However, in the patients with Type II diabetes, hyperglycaemia was experienced for as much as 55+/-7% of the time (13+/-2 h over 24 h) while using the same standardized diet. Breakfast-related hyperglycaemia contributed most (46+/-7%; P<0.01 as determined by ANOVA) to the total amount of hyperglycaemia and postprandial glycaemic instability. In the diabetes patients, blood HbA(1c) content correlated well with the duration of hyperglycaemia and the postprandial glucose responses (P<0.05). In conclusion, CGMS determinations show that standard measurements of glycaemic control underestimate the amount of hyperglycaemia prevalent during real-life conditions in Type II diabetes. Given the macro- and micro-vascular damage caused by postprandial hyperglycaemia, CGMS provides an excellent tool to evaluate alternative therapeutic strategies to reduce hyperglycaemic blood glucose excursions.

Insulinotropic and Muscle Protein Synthetic Effects of Branched-Chain Amino Acids: Potential Therapy for Type 2 Diabetes and Sarcopenia

The loss of muscle mass and strength with aging (i.e., sarcopenia) has a negative effect on functional independence and overall quality of life. One main contributing factor to sarcopenia is the reduced ability to increase skeletal muscle protein synthesis in response to habitual feeding, possibly due to a reduction in postprandial insulin release and an increase in insulin resistance. Branched-chain amino acids (BCAA), primarily leucine, increases the activation of pathways involved in muscle protein synthesis through insulin-dependent and independent mechanisms, which may help counteract the “anabolic resistance” to feeding in older adults. Leucine exhibits strong insulinotropic characteristics, which may increase amino acid availability for muscle protein synthesis, reduce muscle protein breakdown, and enhance glucose disposal to help maintain blood glucose homeostasis.

Poly (ADP-ribose) Polymerase-1–Inhibiting Flavonoids Attenuate Cytokine Release in Blood from Male Patients with Chronic Obstructive Pulmonary Disease or Type 2 Diabetes

Recently, we identified several flavonoids as inhibitors of the nuclear enzyme poly(ADP-ribose) polymerase (PARP)-1 in vitro and in vivo. PARP-1 is recognized as coactivator of nuclear factor-kappaB and plays a role in the pathophysiology of diseases with low-grade systemic inflammation, such as chronic obstructive pulmonary disease (COPD) and type 2 diabetes (T2D). In this study, we assessed the antiinflammatory effects of flavonoids with varying PARP-1-inhibiting effects in whole blood from male patients with COPD or T2D and healthy men. A total of 10 COPD, 10 T2D patients, and 10 healthy volunteers matched for age and BMI were recruited. Blood from each participant was exposed to 1 microg/L lipopolysaccharide (LPS) over 16 h with or without preincubation with 10 micromol/L of flavone, fisetin, morin, or tricetin. Concentrations of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, -8, and -10 were measured in the supernatant. Preincubation with fisetin and tricetin strongly attenuated LPS-induced increases in concentrations of TNFalpha in blood from COPD patients [mean (+/- SEM): -41 +/- 4% (fisetin) and -31 +/- 4% (tricetin); P < 0.001] and IL-6 in blood from T2D patients [-31 +/- 5% (fisetin) and -29 +/- 6% (tricetin); P < or = 0.001]. Moreover, LPS-induced changes in TNFalpha and IL-6 concentrations were positively correlated with the extent of reduction by fisetin and tricetin. The PARP-1-inhibiting flavonoids fisetin and tricetin were able to attenuate LPS-induced cytokine release from leukocytes of patients with chronic systemic inflammation, indicating a potential application as nutraceutical agents for these patient groups.

Postprandial hyperglycemia is highly prevalent throughout the day in type 2 diabetes patients

AIM Although postprandial hyperglycemia is recognized as an important target in type 2 diabetes treatment, information on the prevalence of postprandial hyperglycemia throughout the day is limited. Therefore, we assessed the prevalence of hyperglycemia throughout the day in type 2 diabetes patients and healthy controls under standardized dietary, but otherwise free-living conditions. METHODS 60 male type 2 diabetes patients (HbA(1c) 7.5±0.1% [58±1 mmol/mol]) and 24 age- and BMI-matched normal glucose tolerant controls were recruited to participate in a comparative study of daily glycemic control. During a 3-day experimental period, blood glucose concentrations throughout the day were assessed by continuous glucose monitoring. RESULTS Type 2 diabetes patients experienced hyperglycemia (glucose concentrations >10 mmol/L) 38±4% of the day. Even diabetes patients with an HbA(1c) level below 7.0% (53 mmol/mol) experienced hyperglycemia for as much as 24±5% throughout the day. Hyperglycemia was negligible in the control group (3±1%). CONCLUSION Hyperglycemia is highly prevalent throughout the day in type 2 diabetes patients, even in those patients with a HbA(1c) level well below 7.0% (53 mmol/mol). Standard medical care with prescription of oral blood glucose lowering medication does not provide ample protection against postprandial hyperglycemia.

Protein hydrolysate co-ingestion does not modulate 24 h glycemic control in long-standing type 2 diabetes patients

Objective:Evaluate the efficacy of protein hydrolysate co-ingestion as a dietary strategy to improve blood glucose homeostasis under free-living conditions in long-standing type 2 diabetes patients.Methods:A total of 13 type 2 diabetes patients were enrolled in a randomized, double-blind cross-over design and studied on two occasions for 40 h under strict dietary standardization but otherwise normal, free-living conditions. In one trial, subjects ingested a protein hydrolysate (0.4 g kg−1 bw casein hydrolysate, PRO) with every main meal. In the other trial, a placebo was ingested (PLA). Blood glucose concentrations were assessed by continuous glucose monitoring.Results:Average 24 h glucose concentrations were similar between the PLA and the PRO trials (8.9±0.8 vs 9.2±0.7 mmol l−1, respectively). Hyperglycemia (glucose concentrations >10 mmol l−1) was experienced 34±9% of the time (8±2 h per 24 h) in the PLA trial. Protein hydrolysate co-ingestion with each main meal (PRO) did not reduce the prevalence of hyperglycemia (39±10%, 9±2 h per 24 h; P=0.2).Conclusion:Co-ingestion of a protein hydrolysate with each main meal does not improve glucose homeostasis over a 24 h period in long-standing type 2 diabetes patients.

Protein Co-Ingestion Strongly Increases Postprandial Insulin Secretion in Type 2 Diabetes Patients

The capacity of nutritional protein to induce endogenous insulin secretion has been well established. However, it is not known whether such a response is applicable in a diverse population of type 2 diabetes patients. The aim of the present study was to assess the impact of co-ingesting either intact or hydrolyzed protein with carbohydrate on postprandial plasma insulin and glucose responses in type 2 diabetes patients. Sixty longstanding, male, type 2 diabetes patients participated in a study in which we determined postprandial plasma insulin and glucose responses after ingesting a single bolus of carbohydrate (0.7 g/kg: CHO) with or without an intact protein (0.3 g/kg: PRO) or its hydrolysate (0.3 g/kg: PROh). Results showed that protein co-ingestion strongly increased postprandial insulin release, with the insulin response +99 ± 41 and +110 ± 10% greater in the CHO+PRO and CHO+PROh experiments when compared with the CHO experiment. The insulinotropic properties of protein co-ingestion were evident in nearly all patients, with 58 out of 60 patients responding >10% when compared with the insulin response following carbohydrate ingestion only (CHO). The concomitant plasma glucose responses were 22 ± 32 and 23 ± 36% lower in the CHO+PRO and CHO+PROh experiments, respectively. We conclude that protein co-ingestion represents an effective dietary strategy to strongly augment postprandial insulin release and attenuate the postprandial rise in glucose concentration in type 2 diabetes patients.

Prevalence of daily hyperglycemia in obese type 2 diabetic men compared with that in lean and obese normoglycemic men: effect of consumption of a sucrose-containing beverage

BACKGROUND Hyperglycemia forms a direct and independent risk factor for the development of cardiovascular comorbidities in type 2 diabetes. Consumption of sucrose-sweetened soft drinks might further increase the prevalence of hyperglycemic episodes. OBJECTIVE The objective was to assess glycemic control in type 2 diabetic subjects and healthy lean and obese control subjects under strict dietary standardization but otherwise free-living conditions, with and without the consumption of soft drinks. DESIGN Obese type 2 diabetic men (n = 11) and lean (n = 10) and obese (n = 10) normoglycemic male control subjects participated in a randomized crossover study. The subjects were provided with a standardized diet in 2 periods, during which they consumed 250 mL water with or without (control) sucrose (37.5 g) 2 h after breakfast and lunch. Blood glucose concentrations were assessed by continuous glucose monitoring. RESULTS In the type 2 diabetic subjects, the mean 24-h glucose concentrations were significantly elevated (9.1 +/- 0.6 mmol/L), and hyperglycemia (glucose >10 mmol/L) was evident over 33 +/- 8% (8 +/- 2 h) of a 24-h period (P < 0.01). Hyperglycemia was rarely present in the normoglycemic lean and obese control subjects (5 +/- 2%/24 h for both). Consumption of 75 g sucrose, equivalent to 2 cans of a soft drink, did not further augment the prevalence of hyperglycemia throughout the day in any group. CONCLUSIONS Type 2 diabetic subjects taking oral blood glucose-lowering medication experience hyperglycemia during most of the daytime. Moderate consumption of sucrose-sweetened beverages does not further increase the prevalence of hyperglycemia in type 2 diabetic subjects or in normoglycemic lean or obese men.

Kracht- en duurinspanning verbeteren 24-uurs bloedglucosehomeostase bij personen met een verminderde glucosetolerantie bij patiënten met type 2 diabetes

SamenvattingDe mate van hyperglycemie, en met name postprandiale hyperglycemie, wordt geassocieerd met het risico op diabetesgerelateerde complicaties. Daarom staat glycemische controle centraal bij de behandeling van type 2 diabetes. Fysieke inspanning is bewezen effectief om de glycemische controle te verbeteren bij patiënten met type 2 diabetes.