F. Shojaee-Moradie

Insulin-Sensitizing Effects on Muscle and Adipose Tissue after Dietary Fiber Intake in Men and Women with Metabolic Syndrome

CONTEXT Dietary fibers have been associated with a reduced incidence of type 2 diabetes mellitus in epidemiological studies; however, the precise mechanisms are unknown. OBJECTIVE The objective of the study was to evaluate the efficacy and site of action of an insoluble dietary fiber derived from maize (HAM-RS2) in improving insulin resistance in subjects at increased risk of type 2 diabetes mellitus. DESIGN This study was a randomized, controlled crossover, dietary intervention study. SETTING The study was conducted at the Centre for Diabetes, Endocrinology, and Research, Royal Surrey County Hospital, Guildford, United Kingdom. PARTICIPANTS Fifteen men and women with insulin resistance participated in the study. INTERVENTION The intervention included 40 g/d HAM-RS2 compared with a matched placebo for 8 wk. MAIN OUTCOME MEASURES After each supplement, participants underwent a two-step hyperinsulinemic-euglycemic clamp study with the addition of glucose tracers; a meal tolerance test; arteriovenous sampling across forearm muscle tissue; and a sc adipose tissue biopsy for assessment of gene expression. RESULTS There was enhanced uptake of glucose into the forearm muscle measured by arteriovenous sampling (65 ± 15% increase after resistant starch; P < 0.001). Adipose tissue function was also affected, with enhanced fatty acid suppression after HAM-RS2 treatment and an increase in gene expression for hormone sensitive lipase (P = 0.005), perilipin (P = 0.011), lipoprotein lipase (P = 0.014), and adipose triglyceride lipase (P = 0.03) in biopsy samples. There was no effect on the insulin sensitivity of hepatic glucose production or plasma lipids after HAM-RS2. CONCLUSION HAM-RS2 improved peripheral but not hepatic insulin resistance and requires further study as an intervention in patients with or at risk for type 2 diabetes.

Insulin Detemir Reduces Weight Gain as a Result of Reduced Food Intake in Patients With Type 1 Diabetes

OBJECTIVE Insulin detemir lacks the usual propensity for insulin to cause weight gain. We investigated whether this effect was a result of reduced energy intake and/or increased energy expenditure. RESEARCH DESIGN AND METHODS A 32-week, randomized crossover design trial was undertaken in 23 patients with type 1 diabetes. Patients on a basal-bolus regimen (with insulin aspart as the bolus insulin) were randomly assigned to insulin detemir or NPH insulin as a basal insulin for 16 weeks, followed by the other basal insulin for 16 weeks. At the end of each 16-week period, total energy expenditure, resting energy expenditure, diet-induced thermogenesis, activity energy expenditure, energy intake, weight change, glycemic control, hypoglycemic episodes, and hormones that affect satiety and fuel partitioning were measured. RESULTS After 16 weeks, weight change was −0.69 ± 1.85 kg with insulin detemir and +1.7 ± 2.46 kg with NPH insulin (P < 0.001). Total energy intake was significantly less with insulin detemir (2,016 ± 501 kcal/day) than with NPH insulin (2,181 ± 559 kcal/day) (P = 0.026). There was no significant difference in any measure of energy expenditure, HbA1c percentage, or number of hypoglycemic episodes. Leptin was lower and resistin was higher with insulin detemir compared with NPH insulin (P = 0.039, P = 0.047). After the meal, ghrelin and pancreatic polypeptide levels (P = 0.002, P = 0.001) were higher with insulin detemir. CONCLUSIONS The reduced weight gain with insulin detemir compared with NPH insulin is attributed to reduced energy intake rather than increased energy expenditure. This may be mediated by a direct or indirect effect of insulin detemir on the hormones that control satiety.

Prandial Hypertriglyceridemia in Metabolic Syndrome Is Due to an Overproduction of Both Chylomicron and VLDL Triacylglycerol

The aim was to determine whether fed VLDL and chylomicron (CM) triacylglycerol (TAG) production rates are elevated in metabolic syndrome (MetS). Eight men with MetS (BMI 29.7 ± 1.1) and eight lean age-matched healthy men (BMI 23.1 ± 0.4) were studied using a frequent feeding protocol. After 4 h of feeding, an intravenous bolus of 2H5-glycerol was administered to label VLDL1, VLDL2, and TAG. 13C-glycerol tripalmitin was administered orally as an independent measure of CM TAG metabolism. Hepatic and intestinal lipoproteins were separated by an immunoaffinity method. In MetS, fed TAG and the increment in TAG from fasting to feeding were higher (P = 0.03 and P = 0.04, respectively) than in lean men. Fed CM, VLDL1, and VLDL2 TAG pool sizes were higher (P = 0.006, P = 0.03, and P < 0.02, respectively), and CM, VLDL1, and VLDL2 TAG production rates were higher (P < 0.002, P < 0.05, and P = 0.06, respectively) than in lean men. VLDL1, VLDL2, and CM TAG clearance rates were not different between groups. In conclusion, prandial hypertriglyceridemia in men with MetS was due to an increased production rate of both VLDL and CM TAG. Since both groups received identical meals, this suggests that in MetS the intestine is synthesizing more TAG de novo for export in CMs.

Effects of recombinant human IGF-I/IGF-binding protein-3 complex on glucose and glycerol metabolism in type 1 diabetes.

Recombinant human IGF-I (rhIGF-I) complexed with its natural binding protein IGF-binding protein (IGFBP)-3 (rhIGF-I/IGFBP-3) is a novel formulation that has been shown to improve insulin sensitivity in type 1 diabetes, yet the mechanisms are not clear. We used stable isotopes to investigate the effects of rhIGF-I/IGFBP-3 on glucose and glycerol metabolism in type 1 diabetes. Fifteen subjects (age 13–24 years; 10 males) were studied on three occasions in random order. Each study period lasted for two days, and an injection of either placebo or rhIGF-I/IGFBP-3 (0.1–0.8 mg · kg−1 · day −1) was given subcutaneously at 6:00 p.m. on days 1 and 2. Following the second injection, the subjects were kept euglycemic overnight by a variable rate insulin infusion, followed by a 4-h, two-step (insulin 0.6 and 1.5 mU · kg−1 · min −1) hyperinsulinemic-euglycemic clamp. During the overnight basal steady state, rhIGF-I/IGFBP-3 dose-dependently reduced endogenous glucose production rate (Ra) (P = 0.004), while peripheral glucose uptake (Rd) was not different from placebo. The increase in glucose Rd during hyperinsulinemic clamp was greater following rhIGF-I/IGFBP-3 than placebo, both during the first (P = 0.008) and second step (P = 0.008) of the clamp. No significant differences were found in glycerol Ra, a measure of lipolysis, between rhIGF-I/IGFBP-3 and placebo. In conclusion, rhIGF-I/IGFBP-3 enhances glucose metabolism by controlling both endogenous glucose output and peripheral glucose uptake.

Metabolically healthy and unhealthy obesity: differential effects on myocardial function according to metabolic syndrome, rather than obesity

Background:The term ‘metabolically healthy obese (MHO)’ is distinguished using body mass index (BMI), yet BMI is a poor index of adiposity. Some epidemiological data suggest that MHO carries a lower risk of cardiovascular disease (CVD) or mortality than being normal weight yet metabolically unhealthy.Objectives:We aimed to undertake a detailed phenotyping of individuals with MHO by using imaging techniques to examine ectopic fat (visceral and liver fat deposition) and myocardial function. We hypothesised that metabolically unhealthy individuals (irrespective of BMI) would have adverse levels of ectopic fat and myocardial dysfunction compared with MHO individuals.Subjects:Individuals were categorised as non-obese or obese (BMI ⩾30 kg m−2) and as metabolically healthy or unhealthy according to the presence or absence of metabolic syndrome.Methods:Sixty-seven individuals (mean±s.d.: age 49±11 years) underwent measurement of (i) visceral, subcutaneous and liver fat using magnetic resonance imaging and proton magnetic resonance spectroscopy, (ii) components of metabolic syndrome, (iii) cardiorespiratory fitness and (iv) indices of systolic and diastolic function using tissue Doppler echocardiography.Results:Cardiorespiratory fitness was similar between all groups; abdominal and visceral fat was highest in the obese groups. Compared with age- and BMI-matched metabolically healthy counterparts, the unhealthy (lean or obese) individuals had higher liver fat and decreased early diastolic strain rate, early diastolic tissue velocity and systolic strain indicative of subclinical systolic and diastolic dysfunction. The magnitude of dysfunction correlated with the number of components of metabolic syndrome but not with BMI or with the degree of ectopic (visceral or liver) fat deposition.Conclusions:Myocardial dysfunction appears to be related to poor metabolic health rather than simply BMI or fat mass. These data may partly explain the epidemiological evidence on CVD risk relating to the different obesity phenotypes.

Comparison of Body Mass Index and Waist/Height Ratio in Predicting Definite Coronary Artery Disease

Background: Body mass index (BMI), waist circumference (WC), waist/hip ratio, waist/height ratio (WHtR) and skin fold thickness are clinical tools enabling the evaluation of obesity. WHtR is a recently introduced index to assess central fat distribution. This study was performed to compare the prognostic value of WHtR and BMI for definite coronary artery disease (CAD). Methods: A cross-sectional study was performed in the Shahid-Chamran Hospital, Isfahan, Iran. The study included 591 patients undergoing coronary angiography for suspected ischemia. We measured BMI, WC and coronary artery scores of the patients. Prevalence of CAD was compared between obese (BMI ≥30) and abdominal obese (WHtR ≥0.55) participants. Results: Prevalence of CAD was significantly higher in abdominal obese patients (WHtR ≥0.55) than in patients without abdominal obesity (odds ratio, OR = 1.63, p = 0.008). The difference in CAD prevalence between obese (BMI ≥30) and non-obese patients nearly reached significance (OR = 1.48, p = 0.058). There was a significant positive correlation between CAD score and age (p < 0.01), WC (p < 0.05), and WHtR (p < 0.01) in male participants. Conclusion: WHtR may be a better marker of central obesity and may better predict CAD than BMI and WC.

Dissociation between exercise-induced reduction in liver fat and changes in hepatic and peripheral glucose homoeostasis in obese patients with non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) is associated with multi-organ (hepatic, skeletal muscle, adipose tissue) insulin resistance (IR). Exercise is an effective treatment for lowering liver fat but its effect on IR in NAFLD is unknown. We aimed to determine whether supervised exercise in NAFLD would reduce liver fat and improve hepatic and peripheral (skeletal muscle and adipose tissue) insulin sensitivity. Sixty nine NAFLD patients were randomized to 16 weeks exercise supervision (n=38) or counselling (n=31) without dietary modification. All participants underwent MRI/spectroscopy to assess changes in body fat and in liver and skeletal muscle triglyceride, before and following exercise/counselling. To quantify changes in hepatic and peripheral insulin sensitivity, a pre-determined subset (n=12 per group) underwent a two-stage hyperinsulinaemic euglycaemic clamp pre- and post-intervention. Results are shown as mean [95% confidence interval (CI)]. Fifty participants (30 exercise, 20 counselling), 51 years (IQR 40, 56), body mass index (BMI) 31 kg/m(2) (IQR 29, 35) with baseline liver fat/water % of 18.8% (IQR 10.7, 34.6) completed the study (12/12 exercise and 7/12 counselling completed the clamp studies). Supervised exercise mediated a greater reduction in liver fat/water percentage than counselling [Δ mean change 4.7% (0.01, 9.4); P<0.05], which correlated with the change in cardiorespiratory fitness (r=-0.34, P=0.0173). With exercise, peripheral insulin sensitivity significantly increased (following high-dose insulin) despite no significant change in hepatic glucose production (HGP; following low-dose insulin); no changes were observed in the control group. Although supervised exercise effectively reduced liver fat, improving peripheral IR in NAFLD, the reduction in liver fat was insufficient to improve hepatic IR.

Effect of 6-month supervised exercise on low-density lipoprotein apolipoprotein B kinetics in patients with type 2 diabetes mellitus

Although low-density lipoprotein (LDL) cholesterol is often normal in patients with type 2 diabetes mellitus, there is evidence for a reduced fractional catabolic rate and consequently an increased mean residence time (MRT), which can increase atherogenic risk. The dyslipidemia and insulin resistance of type 2 diabetes mellitus can be improved by aerobic exercise, but effects on LDL kinetics are unknown. The effect of 6-month supervised exercise on LDL apolipoprotein B kinetics was studied in a group of 17 patients with type 2 diabetes mellitus (mean age, 56.8 years; range, 38-68 years). Patients were randomized into a supervised group, who had a weekly training session, and an unsupervised group. LDL kinetics were measured with an infusion of 1-(13)C leucine at baseline in all groups and after 6 months of exercise in the patients. Eight body mass index-matched nondiabetic controls (mean age, 50.3 years; range, 40-67 years) were also studied at baseline only. At baseline, LDL MRT was significantly longer in the diabetic patients, whereas LDL production rate and fractional clearance rates were significantly lower than in controls. Percentage of glycated hemoglobin A(1c), body mass index, insulin sensitivity measured by the homeostasis model assessment, and very low-density lipoprotein triglyceride decreased (P < .02) in the supervised group, with no change in the unsupervised group. After 6 months, LDL cholesterol did not change in either the supervised or unsupervised group; but there was a significant change in LDL MRT between groups (P < .05) that correlated positively with very low-density lipoprotein triglyceride (r = 0.51, P < .04) and negatively with maximal oxygen uptake, a measure of fitness (r = -0.51, P = .035), in all patients. The LDL production and clearance rates did not change in either group. This study suggests that a supervised exercise program can reduce deleterious changes in LDL MRT.

The effect of an intravenous infusion of IGF‐I and insulin on IGFBP‐1, IGFBP‐3, acid labile subunit, free and bound IGF‐I, catecholamines and potassium in normal volunteers during an amino acid and glucose clamp

To investigate the effects of IGF‐I and insulin at doses equipotent with respect to hypoglycaemic effect on IGF‐I concentrations (free and bound), IGF binding proteins, catecholamines and potassium levels.

Increased Insulin Sensitivity by Metformin Enhances Intense-Pulsed-Light-Assisted Hair Removal in Patients with Polycystic Ovary Syndrome

Background: Polycystic ovary syndrome (PCOS) is an insulin-resistant state with hirsutism as a common manifestation. Objective: We hypothesized that treatment with metformin would improve the cosmetic effects of intense pulsed light (IPL) therapy for hair removal in PCOS patients. Methods: In a prospective randomized controlled trial, 70 PCOS patients randomly received metformin (1,500 mg daily) + IPL therapy or IPL therapy alone for 5 IPL sessions during a 6-month period, followed by an additional 6 months of observation. Hirsutism score, homeostasis model assessment for insulin resistance (HOMA-IR), free androgen index (FAI) and patient satisfaction were evaluated at every visit. Results: Fifty-two patients finished the study. Hirsutism was significantly better controlled in the metformin group (p = 0.009). Patient satisfaction was significantly better in the metformin group at the end of the observation period (52.9 vs. 34.1%, p = 0.019). HOMA-IR and FAI scores improved after metformin + IPL treatment (p < 0.05). Conclusion: Adding metformin to IPL in women with PCOS results in a significant improvement in insulin sensitivity and hirsutism.