Effect of exercise on postprandial insulin responses in Mexican American and non-Hispanic women.

Postprandial insulin responses (integrated area under the curve) to an oral glucose load after a period of aerobic exercise and no exercise (control) were compared in sedentary normoglycemic Mexican American and non-Hispanic women pair-matched (n = 9) on total body fat mass (21.8 +/- 3.5 kg). The age (27.4 +/- 3.0 years), body mass index (BMI) (23.6 +/- 1.4 kg/m2), waist to hip ratio (WHR) (0.85 +/- .02), waist circumference (83.5 +/- 4.5 cm), lean mass (36.2 +/- 1.5 kg), and maximal O2 consumption ([VO2 max] 32.9 +/- 1.6 mL x kg(-1) x min(-1)) were similar, although the centrality index (subscapular/triceps skinfolds) was significantly greater in Mexican Americans (0.88 +/- 0.06 v 0.70 +/- 0.05, P < .01). Exercise (treadmill walking for 50 minutes at 70% VO2 max) and control trials were performed 4 weeks apart and 5 to 12 days after the onset of menstruation. A 75-g oral glucose load was administered 15 hours after the completion of each trial, with the subjects 12 hours postprandial. Blood samples were drawn prior to glucose ingestion (fasting, 0 minutes) and at minutes 15, 30, 60, 90, 120, and 150 postingestion. The postprandial insulin response was calculated using a trapezoidal method. In Mexican Americans, significant (P < .02) reductions in the postprandial insulin response (exercise v control, 6.5 +/- 1.0 v 8.5 +/- 1.4 pmol/L x min x 10(4)) and fasting insulin (exercise v control, 77.4 +/- 7.0 v 88.5 +/- 10.3 pmol/L) occurred after exercise compared with the control condition. In non-Hispanics, neither the postprandial insulin response (exercise v control, 7.2 +/- 1.0 v 6.2 +/- 0.9 pmol/L x min x 10(4)) nor fasting insulin (exercise v control, 77.0 +/- 8.2 v 82.9 +/- 8.9 pmol/L) were significantly different between trials. The postprandial insulin response in the control trial was significantly correlated with the change in the insulin response (control minus exercise) in the 18 women (r = .56, P = .01). No trial or group differences were found for postprandial glucose and C-peptide responses. Mexican American women have a high risk of developing type 2 diabetes, and aerobic exercise may be valuable in the prevention or delay of onset of diabetes by reducing peripheral insulin resistance.     

Effects of weight loss in obese subjects with normal fasting plasma glucose or impaired glucose tolerance on insulin release and insulin resistance according to a minimal model analysis

We investigated effects of weight loss from diet and exercise regimen in obese subjects with normal fasting plasma glucose or impaired glucose tolerance (IGT) on insulin release capacity and insulin sensitivity. Eight subjects were recruited among visceral obesity patients (4 men, 4 women; age range, 24 to 57 years; body mass index [BMI], 32.8 to 60.3 kg/m(2)). All were admitted to Chiba University Hospital for 2 weeks, were treated with a tapering 5,023 to 2,930 kJ diet, and were given exercise equivalent to 628 kJ/d. For assessments, we used a combination of C-peptide secretion rate determination and minimal model analysis as previously reported. BMI and visceral fat area (V) significantly decreased (BMI on initiation v after intervention, 43.0 +/- 3.2 v 40.3 +/- 3.1 kg/m(2), P <.05; V, 224 +/- 22 v 188 +/- 22 cm(2); P <.05). Fasting immunoreactive insulin (F-IRI) and leptin concentrations decreased significantly. Capacity for insulin release in response to glucose increased in all subjects (first-phase insulin secretion [CS1], 4.66 +/- 4.05 v 6.81 +/- 4.57 ng/mL/5 min, P <.05), but the insulin sensitivity index (S(i)) did not change significantly. These data suggest that weight reduction early in development of type 2 diabetes can oppose progression of diabetes by improving capacity for insulin release.     

Effect of resistance training with or without chromium picolinate supplementation on glucose metabolism in older men and women.

The effect of 12 weeks of resistance training (RT) with or without chromium picolinate (Cr-pic) supplementation on glucose tolerance was assessed in moderately overweight older men and women (age, 62 +/- 4 years; body mass index [BMI], 29.1 +/- 2.5 kg/m2). Seventeen men and 15 women were randomized to groups that consumed either 17.8 micromol chromium per day (924 microg Cr/d) as Cr-pic or a placebo (<0.1 microg Cr/d) while performing RT twice weekly. For all 32 subjects combined, fasting glucose increased but there were no changes in insulin or C-peptide concentrations after 12 weeks of RT. In response to an oral glucose challenge, the glucose and C-peptide areas under the curve (AUCs) were unchanged, whereas there was a 19% decrease in the insulin AUC (from 68 +/- 53 to 55 +/- 29 x 10(3) pmol/L/180 min, P = .045). The RT responses for the fasting concentration or AUC for glucose, insulin, or C-peptide were not influenced by Cr-pic. The decrease in the insulin AUC without any change in insulin secretion, as evidenced by a lack of change in the C-peptide AUC, suggests enhanced insulin clearance from the circulation with RT. Collectively, these data suggest that RT decreases the insulin response following an oral glucose challenge in older moderately overweight men and women without affecting glucose tolerance. The data also suggest that the decrease in circulating insulin may result from an increase in insulin clearance, not a decrease in insulin secretion. High-dose Cr-pic supplementation had no effect on any measure of glucose metabolism during RT.     

Increase in plasma pollutant levels in response to weight loss is associated with the reduction of fasting insulin levels in men but not in women

Environmental pollutants can act as endocrine modulators. In this study, we examined whether weight loss-induced changes in plasma organochlorine compounds (OC) were associated with those in plasma insulin levels. Fasting insulin and the area under the curve (AUC) of insulin after a 75-g oral glucose load, plasma levels of 1 commercial polychlorinated biphenyl (PCB) mixture (Aroclor 1260), 1 PCB congener (PCB 153), and 3 pesticides (2,2'-bis(4-chlorophenyl)-1,1-dichloroethylene (p,p'-DDE), beta-hexachlorocyclohexane (beta-HCH), and hexachlorobenzene (HCB)) were measured before and after a 15-week weight loss program induced by a caloric restriction in a sample of obese men and women. Both genders showed a similar reduction in body weight (approximately 11 kg) in response to treatment, although men lost significantly more fat mass than women (mean +/- SD 9.4 +/- 4.1 v 5.9 +/- 5 kg, respectively, P <.05). Fasting insulin and AUC of insulin significantly decreased in men and women after the treatment. In response to weight loss, a significant increase in OC was observed in both genders, and this effect was more pronounced in men. The greater the increase in plasma OC levels, the greater the reduction in fasting insulin was in response to weight loss in men (-.49 < r < -.59, P <.05), but not in women (-.22 < r <.01, not significant [NS]). In both genders, no relationship was observed between changes in plasma OC levels and changes in AUC of insulin (-.41 < r < -.08, NS). In men, relationships between changes in plasma HCB, Aroclor 1260, and PCB-153 concentrations and those in fasting insulin levels in response to weight loss remained significantly correlated after correction for fat mass loss (-.46 < partial r < -.51, P values ranging from.05 to.07). These results suggest that weight loss-induced increase in plasma pollutant levels tends to be independently associated with the reduction of fasting insulin levels in men, but not in women. Further studies are needed to verify whether these findings are causally related.     

Adipose tissue, hepatic, and skeletal muscle insulin sensitivity in extremely obese subjects with acanthosis nigricans

We evaluated insulin action in skeletal muscle (glucose disposal), liver (glucose production), and adipose tissue (lipolysis) in 5 extremely obese women with acanthosis nigricans (AN), who had normal oral glucose tolerance, and 5 healthy lean subjects, by using a 5-stage pancreatic clamp and stable isotopically labeled tracer infusion. Basal plasma insulin concentration was much greater in obese subjects with AN than lean subjects (54.8 +/- 4.5 vs 8.0 +/- 1.3 microU/mL, P < .001), but basal glucose and free fatty acid concentrations were similar in both groups. During stage 1 of the clamp, glucose rate of appearance (R(a)) (2.6 +/- 0.3 vs 3.7 +/- 0.3 micromol x kg FFM(-1) x min(-1), P = .02) and palmitate R(a) (2.4 +/- 0.6 vs 7.0 +/- 1.5 micromol x kg FFM(-1) x min(-1), P < .05) were greater in obese subjects with AN than lean subjects despite slightly greater plasma insulin concentration in subjects with AN (3.0 +/- 0.7 vs 1.1 +/- 0.4 microU/mL, P < .05). The area under the curve for palmitate R(a) (1867 +/- 501 vs 663 +/- 75 micromol x kg FFM(-1) x 600 min(-1), P = .03) and glucose R(a) (1920 +/- 374 vs 1032 +/- 88 micromol x kg FFM(-1) x 600 min(-1), P = .02) during the entire clamp procedure was greater in subjects with AN than lean subjects. During intermediate insulin conditions (plasma insulin, approximately 35 microU/mL), palmitate R(a) was 5-fold greater in subjects with AN than in lean subjects (2.6 +/- 1.1 vs 0.5 +/- 0.2 micromol x kg FFM(-1) x min(-1), P = .05). Maximal glucose disposal was markedly lower in obese subjects with AN than in lean subjects (13.0 +/- 0.8 vs 23.4 +/- 1.8 mg x kg FFM(-1) x min(-1), P = .01) despite greater peak plasma insulin concentration (1842 +/- 254 vs 598 +/- 38 microU/mL, P < .05). These data demonstrate obese young adults with AN have marked insulin resistance in multiple tissues. However, marked insulin hypersecretion can compensate for impaired insulin action, resulting in normal glucose and fatty acid metabolism during basal conditions.     

Interactions between energy surplus and short-term exercise on glucose and insulin responses in healthy people with induced, mild insulin insensitivity

Short-term exercise can enhance insulin action, but the effect may be negated by the opposing action of energy surplus. The purpose of this investigation was to test the hypothesis that a single exercise bout would increase insulin action, even when opposed by a concurrent energy surplus. After 2 days in energy balance without exercise, baseline glucose and insulin areas under the curve and the insulin sensitivity index (C-ISI) were measured during an oral glucose tolerance test in 9 healthy, habitually active subjects (6 males, 3 females). A state of relative insulin insensitivity was then induced by systematic overfeeding (OF) to generate a daily energy surplus of 768 +/- 203 kcal/d for 3 days, and the oral glucose tolerance test was repeated. In the following 24 hours, the OF was increased approximately 2-fold (+6284 +/- 1669 kJ/d) and subjects performed a single bout of exercise (expenditure = 3063 +/- 803 kJ) to maintain the same energy surplus (+3125 +/- 933 kJ/d; OF and exercise) as OF. After OF, fasting insulin tended to be higher (+36%, P = .099), insulin AUC rose by 38% (P = .002), and C-ISI declined from 6.6 +/- 3.1 to 4.6 +/- 1.8 (P = .007) compared with baseline. After OF and exercise, fasting insulin remained elevated (+43% compared with baseline; P = .043) and C-ISI rose only slightly (4.6 +/- 1.8 to 5.2 +/- 2.3; P = .058), but insulin AUC declined by 20% (P = .048) compared with OF. A single exercise bout, opposed by a concurrent energy surplus, decreased the insulin response to a glucose challenge, but only partially restored the insulin AUC to baseline and had no impact on C-ISI or fasting insulin concentrations.     

Influence of melatonin administration on glucose tolerance and insulin sensitivity of postmenopausal women

OBJECTIVE: The effect of melatonin on human carbohydrate metabolism is not yet clear. We investigated whether melatonin influences glucose tolerance and insulin sensitivity in aged women. PATIENTS: Twenty-two postmenopausal women of whom 14 were on hormone replacement therapy. DESIGN: After an overnight fast, at 0800 hours on two nonconsecutive days, placebo or melatonin (1 mg) were administered randomly and in a double blind fashion. Forty-five minutes later, an oral glucose tolerance test (75 g; OGTT) was performed in 13 women. In another nine women insulin-dependent (Si) and -independent (Sg) glucose utilization was tested by a frequently sampled intravenous glucose tolerance test (FSIGT). RESULTS: Areas under the response curve to OGTT (AUC) for glucose (1420 +/- 59 vs. 1250 +/- 55 mmol x min/l; P < 0.01), and C-peptide (42,0980 +/- 45,320 vs. 33,528 +/- 15,779 pmol x min/l; P < 0.02) were higher following melatonin than placebo, while Si values were lower (2.6 +/- 0.28 units vs. 3.49 +/- 0.4 units; P < 0.03). Si modifications induced by melatonin were inversely related to Si values of the placebo day (r(2) = 0.538; P < 0.025). CONCLUSIONS: The present results indicate that in aged women administration of 1 mg of melatonin reduces glucose tolerance and insulin sensitivity. The present data may have both physiological and clinical implications.     

Effect of short-term exercise training on leptin and insulin action

The purpose of the study was to determine the effect of short-term exercise training (7 consecutive days for 60 min/d at 75% maximal oxygen consumption [VO2 max]), which did not change body mass on fasting plasma leptin concentration and insulin action. Young, lean subjects (n = 16; age, 21.9 +/- 0.6 years; body fat, 17.5% +/- 1.5%) and older subjects with relatively more adipose tissue (n = 14; age, 58.6 +/- 1.4 years; body fat, 28.3% +/- 1.3%) were studied (mean +/- SE). Fasting plasma leptin was significantly (P < .05) related to adiposity (fat mass, r = .58; % body fat, r = .76) in this population. Body mass did not change (P < .05) in any of the groups with training (71.8 +/- 2.5 v 71.9 +/- 2.5 kg). The insulin sensitivity index (SI determined from an intravenous glucose tolerance test (IVGTT) improved significantly (P < .05) in both the young group (4.8 +/- 0.6 v6.9 +/- 0.8 x 10(-4)/ min (microU/mL) and the older group (3.2 +/- 0.6 v 5.9 +/- 1.0 x 10(-4)/min (microU/mL)). Fasting leptin did not change with training in either group (10.4 +/- 1.6 v 9.2 +/- 1.0 ng/mL). These findings suggest that exercise does not independently affect the fasting plasma leptin concentration and the improvement in insulin action with exercise is not associated with an alteration in fasting leptin in healthy sedentary lean and relatively lean subjects.     

Carbohydrate metabolism during exercise in females: effect of reduced fat availability

This study examined the effect of reduced plasma free fatty acid (FFA) availability on carbohydrate metabolism during exercise. Six untrained women cycled for 60 minutes at approximately 58% of maximum oxygen uptake after ingestion of a placebo (CON) or nicotinic acid (NA), 30 minutes before exercise (7.4 +/- 0.5 mg.kg(-1) body weight), and at 0 minutes (3.7 +/- 0.3 mg.kg(-1)) and 30 minutes (3.7 +/- 0.3 mg.kg(-1)) of exercise. Glucose kinetics were measured using a primed, continuous infusion of [6,6-(2)H] glucose. Plasma FFA (CON, 0.86 +/- 0.12; NA, 0.21 +/- 0.11 mmol.L(-1) at 60 minutes, P <.05) and glycerol (CON, 0.34 +/- 0.05; NA, 0.10 +/- 0.04 mmol.L(-1) at 60 minutes, P <.05) were suppressed throughout exercise. Mean respiratory exchange ratio (RER) during exercise was higher (P <.05) in NA (0.89 +/- 0.02) than CON (0.83 +/- 0.02). Plasma glucose and glucose production were similar between trials. Total glucose uptake during exercise was greater (P <.05) in NA (1,876 +/- 161 micromol.kg(-1)) than in CON (1,525 +/- 107 micromol.kg(-1)). Total fat oxidation was reduced (P <.05) by approximately 32% during exercise in NA. Total carbohydrate oxidized was approximately 42% greater (P <.05) in NA (412 +/- 40 mmol) than CON (290 +/- 37 mmol), of which, approximately 16% (20 +/- 10 mmol) could be attributed to glucose. Plasma insulin and glucagon were similar between trials. Catecholamines were higher (P <.05) during exercise in NA. In summary, during prolonged moderate exercise in untrained women, reduced FFA availability results in a compensatory increase in carbohydrate oxidation, which appears to be due predominantly to an increase in glycogen utilization, although there was a small, but significant, increase in whole body glucose uptake.     

The effects of short-term overfeeding on insulin action in lean and reduced-obese individuals

Insulin resistance is clearly associated with obesity. However, the role of excess energy intake per se as opposed to increased fat mass in the development of insulin resistance has not been clearly defined. It may be that the nutrient load provided by short-term overfeeding is sufficient to induce measurable changes in insulin action in skeletal muscle and the liver. We examined the effects of 3 days of overfeeding on insulin action and glucose kinetics in 13 lean (body mass index, 20.9 +/- 2.4 kg/m(2); 6 men, 7 women) and 9 reduced-obese (RO) (body mass index, 29.1 +/- 2.2 kg/m(2); 4 men, 5 women) individuals. A two-step euglycemic hyperinsulinemic clamp study (5 and 40 mU m(-2) min(-1)) with a primed, constant infusion of [6,6-(2)H(2)]glucose was performed after 3 days of a weight-maintenance diet and again after 3 days of overfeeding by 50% (50% carbohydrate, 30% fat, 20% protein). At baseline, lean individuals were more insulin sensitive, as measured by glucose infusion rate, than RO individuals (12.08 +/- 0.8 vs 7.62 +/- 1.0 mg x kg(-1) x min(-1), P < .01) with lean women being more insulin sensitive than lean men (P < .01). Overfeeding resulted in a reduction in glucose infusion rate in lean women (13.37 +/- 1.3 to 11.42 +/- 1.0 mg x kg(-1) x min(-1), P < .05), but no change was noted in lean men or RO individuals. Basal and insulin-stimulated glucose disposal remained unchanged with overfeeding in all groups. Low-dose insulin suppression of endogenous glucose production was impaired after overfeeding in lean women (euenergetic, 1.92 +/- 0.36 to 0.36 +/- 0.16 mg x kg(-1) x min(-1); overfeeding: 2.13 +/- 0.17 to 0.86 +/- 0.12 mg x kg(-1) x min(-1); P = .04) but remained unchanged in the other groups. These findings demonstrate that insulin action is reduced in lean, obese-resistant women after short-term overfeeding primarily because of an inhibition of insulin-mediated suppression of endogenous glucose production, whereas short-term overfeeding does not appear to effect insulin action in lean men and RO individuals. This response may be indirectly involved in the ability of lean women to maintain weight in the face of an obesigenic environment.     

Evidence of a state of increased insulin resistance in preeclampsia.

Similarities in certain biochemical variables between preeclampsia and the insulin resistance syndrome imply a possible link between insulin resistance and preeclampsia. We measured insulin sensitivity by the minimal model technique between 29 and 39 weeks of gestation in 22 preeclamptic and 16 control women, whose glucose tolerance was first confirmed as normal by an oral glucose tolerance test. In addition, we measured the fasting levels of serum C-peptide, uric acid, lipids, and lipoproteins. Preeclamptic women showed a higher insulin response (P = .001) during the oral glucose tolerance test than the controls. Insulin sensitivity in preeclamptic women (1.11+/-0.15 x 10(-4) x min(-1) x microU/mL) was 37% lower (P = .009) than in control women (1.77+/-0.19 x 10(-4) x min(-1) x microU/mL). The free fatty acid (FFA) concentration in preeclamptic women (0.17+/-0.01 g/L, P = .0004) was 70% higher than in control women (0.10+/-0.01 g/L). Also, baseline serum levels of C-peptide, uric acid, and triglyceride were higher in preeclamptic women. Insulin sensitivity increased fourfold to fivefold within the first 3 postpartum months, but insulin sensitivity in preeclamptic women was still 26% lower (P = .04) than in control women. Preeclampsia is a state of increased insulin resistance, and it persists for at least 3 months after pregnancy. This may be a pathogenetic factor in preeclampsia and may contribute to the excess cardiovascular morbidity among women with prior preeclampsia.     

Decreased urinary calcium loss and lower bone turnover in young oral contraceptive users

The effect of ethinyl estradiol-containing oral contraceptives (OCs) on bone health is still not completely understood. This study was therefore performed to investigate the effect of OC use on biochemical parameters of calcium (Ca) and bone metabolism in young women. Twelve OC users ([OC+ group] age, 24.8 +/- 0.6 years) and 19 eumenorrheic nonusers ([OC-group] age, 25.5 +/- 0.8 years) were studied. Three individual urine samples (fasting 2-hour and 24-hour specimen) and 3 blood samples collected at intervals of 28 days were pooled for data evaluation. Energy, nutrient intake (7-day food record), the body mass index, and serum 25-hydroxyvitamin D levels of the 2 groups were comparable. Serum levels of estradiol (E2) and sex hormone-binding globulin (SHBG) in the 2 groups mirrored the use and nonuse of OCs. Fasting 2-hour renal Ca excretion was markedly lower in the OC+ group compared with the OC- group (80.2 +/- 14.7 v 185.1 +/- 18.8 micromol/mmol creatinine [Cr], P < .001), indicating a decrease in the urinary loss of endogenous, bone-derived Ca. Moreover, 24-hour renal Ca excretion was reduced in the OC+ group (3.65 +/- 1.46 v5.03 +/- 1.90 mmol/d, respectively, P < .01). In addition, serum Ca levels were lower in the OC+ group versus the OC- group (2.19 +/- 0.07 v 2.29 +/- 0.02 mmol/L; P < .05). The OC+ group had lower serum levels of carboxy-terminal propeptide of type I procollagen ([PICP] a biomarker of bone formation) compared with the OC- group (78.3 +/- 3.6 ng/mL in the OC+ group v 96.9 +/- 5.5 ng/mL in the OC- group, P < .001) and lower renal hydroxyproline (OHPr) excretion (a biomarker of bone resorption, 8.3 +/- 1.0 v 11.3 +/- 1.0 micromol/mmol, Cr, P < .001). In summary, OCs reduce urinary Ca loss and slow bone turnover in young women. The results may help to explain the OC effect on bone mass in young women.     

Beneficial effects of metformin in normoglycemic morbidly obese adolescents

Hyperinsulinemia and insulin resistance are common features of obesity in humans and experimental animals. It has been demonstrated that metformin, an antihyperglycemic agent, decreases hyperinsulinemia and insulin resistance leading to decreased adiposity in obese and non-insulin-dependent diabetes mellitus (NIDDM) adults. To evaluate the antiobesity effect of metformin, we conducted a randomized double-blind placebo controlled trial in 24 hyperinsulinemic nondiabetic obese adolescents (body mass index [BMI] >30 kg/m(2)). All subjects were placed on a low-calorie (1,500 kcal for women and 1,800 kcal for men) meal plan. After an initial 1-week lead-in period, 12 subjects (mean +/- SE for age and BMI, 15.6 +/- 0.4 and 41.2 +/- 1.8, respectively) received metformin (850 mg twice daily) for 8 weeks, and 12 subjects (mean +/- SE for age and BMI, 15.7 +/- 0.5 and 40.8 +/- 1.4, respectively) received placebo. Compared to the placebo group, the metformin group had greater weight loss (6.5% +/- 0.8% v 3.8 +/- 0.4%, P <.01), greater decrease in body fat (P <.001), greater increase in fat-free mass to body fat ratio (P <.005), and greater attenuation of area under the curve (AUC) insulin response to an oral glucose tolerance test (P <.001). This was associated with enhanced insulin sensitivity, as determined by the fasting plasma glucose:insulin, 2-hour glucose:insulin, and AUC glucose:AUC insulin ratios, in the metformin group compared to controls (P <.01). This corresponded to a significant reduction in plasma leptin (P <.005), cholesterol, triglycerides, and free fatty acid (FFA) levels (P <.05) only in the metformin-treated subjects. Combined metformin treatment and low-calorie diet had a significant antiobesity effect in hyperinsulinemic obese adolescents compared to a low-calorie diet alone.     

Skeletal muscle neuronal nitric oxide synthase micro protein is reduced in people with impaired glucose homeostasis and is not normalized by exercise training

Skeletal muscle inducible nitric oxide synthase (NOS) protein is greatly elevated in people with type 2 diabetes mellitus, whereas endothelial NOS is at normal levels. Diabetic rat studies suggest that skeletal muscle neuronal NOS (nNOS) micro protein expression may be reduced in human insulin resistance. The aim of this study was to determine whether skeletal muscle nNOSmicro protein expression is reduced in people with impaired glucose homeostasis and whether exercise training increases nNOSmicro protein expression in these individuals because exercise training increases skeletal muscle nNOSmicro protein in rats. Seven people with type 2 diabetes mellitus or prediabetes (impaired fasting glucose and/or impaired glucose tolerance) and 7 matched (sex, age, fitness, body mass index, blood pressure, lipid profile) healthy controls aged 36 to 60 years participated in this study. Vastus lateralis muscle biopsies for nNOSmicro protein determination were obtained, aerobic fitness was measured (peak pulmonary oxygen uptake [Vo(2) peak]), and glucose tolerance and insulin homeostasis were assessed before and after 1 and 4 weeks of cycling exercise training (60% Vo(2) peak, 50 minutes x 5 d wk(-1)). Skeletal muscle nNOSmicro protein was significantly lower (by 32%) in subjects with type 2 diabetes mellitus or prediabetes compared with that in controls before training (17.7 +/- 1.2 vs 26.2 +/- 3.4 arbitrary units, P < .05). The Vo(2) peak and indicators of insulin sensitivity improved with exercise training in both groups (P < .05), but there was no effect of exercise training on skeletal muscle nNOSmicro protein in either group. In conclusion, individuals with impaired glucose homeostasis have reduced skeletal muscle nNOSmicro protein content. However, because exercise training improves insulin sensitivity without influencing skeletal muscle nNOSmicro protein expression, it seems that changes in skeletal muscle nNOSmicro protein are not central to the control of insulin sensitivity in humans and therefore may be a consequence rather than a cause of diabetes.     

Osteocalcin and glucose metabolism in postmenopausal women subjected to aerobic training program for 8 weeks

Results of animal studies suggest that osteocalcin (OC) plays an important role in the regulation of carbohydrate metabolism. The aim of the present study was to assess the relationship between biochemical indices of bone turnover and carbohydrate metabolism in postmenopausal women subjected to aerobic training for 8 weeks. The study was conducted on 44 postmenopausal women: 27 of them participated in the training program, and 17 did not undertake any additional physical activity during the study period (control group). Subjects performed a cycle-ergometer physical workout at a level of 70% to 80% of ventilatory threshold intensity for 8 weeks (40-minute sessions, 3 times per week). Serum concentrations of OC, C-terminal telopeptide of type I collagen, osteoprotegerin (OPG), insulin, and glucose were measured; and the homeostasis model assessment of insulin resistance index (HOMA-IR) was calculated before and after the 8-week training program. The training program caused significant decrease in levels of OC (P < .05), HOMA-IR (P < .05), and waist-to-hip ratio (P < .05). No significant changes were observed in C-terminal telopeptide of type I collagen, OPG, insulin, and glucose concentrations. Pretraining OC levels inversely correlated with concentrations of OPG (P < .05), glucose (P < .05), and insulin (P < .05) and with HOMA-IR values (P < .05). Our study revealed an association between serum OC concentrations and metabolic markers in postmenopausal women. Regular physical activity was associated with decrease in central adiposity and OC levels and slight reduction of insulin resistance. However, no direct relationships between training-related changes in OC concentrations and metabolic markers were observed.     

Effects of nateglinide on the secretion of glycated insulin and glucose tolerance in type 2 diabetes

AIMS: Glycation of insulin has been demonstrated within pancreatic beta-cells and the resulting impaired bioactivity may contribute to insulin resistance in diabetes. We used a novel radioimmunoassay to evaluate the effect of nateglinide on plasma concentrations of glycated insulin and glucose tolerance in type 2 diabetes. METHODS: Ten patients (5 M/5 F, age 57.8+/-1.9 years, HbA(1c) 7.6+/-0.5%, fasting plasma glucose 9.4+/-1.2 mmol/l, creatinine 81.6+/-4.5 microM/l) received oral nateglinide 120 mg or placebo, 10 min prior to 75 g oral glucose in a random, single blind, crossover design, 1 week apart. Blood samples were taken for glycated insulin, glucose, insulin and C-peptide over 225 min. RESULTS: Plasma glucose and glycated insulin responses were reduced by 9% (P=0.005) and 38% (P=0.047), respectively, following nateglinide compared with placebo. Corresponding AUC measures for insulin and C-peptide were enhanced by 36% (P=0.005) and 25% (P=0.007) by nateglinide. CONCLUSIONS: Glycated insulin in type 2 diabetes is reduced in response to the insulin secretagogue nateglinide, resulting in preferential release of native insulin. Since glycated insulin exhibits impaired biological activity, reduced glycated insulin release may contribute to the antihyperglycaemic action of nateglinide.     

Influence of resistance exercise training on glucose control in women with type 2 diabetes

The objective of the study was to evaluate the effects of acute and chronic resistance training on glucose and insulin responses to a glucose load in women with type 2 diabetes. Subjects consisted of type 2 diabetic women (n = 7) and age-matched controls (n = 8) with normal glucose tolerance. All subjects participated in 3 oral glucose tolerance tests: pretraining, 12 to 24 hours after the first exercise session (acute) and 60 to 72 hours after the final training session (chronic). Exercise training consisted of a whole body resistance exercise program using weight-lifting machines 3 days per week for 6 weeks. Resistance training was effective in increasing strength of all muscle groups in all subjects. Integrated glucose concentration expressed as area under the curve (AUC) was 3,355.0 +/- 324.6 mmol/L. min pretraining, improved significantly (P <.01) after the acute bout of exercise (2,868 +/- 324.0 mmol/L. min), but was not improved with chronic training (3,206.0 +/- 337.0 mmol/L. min) in diabetic subjects. A similar pattern of significance was observed with peak glucose concentration (pre: 20.2 +/-1.4 mmol/L; acute: 17.2 +/- 1.7 mmol/L; chronic: 19.9 +/- 1.7 mmol/L). There were no significant changes in insulin concentrations after any exercise bout in the diabetic subjects. There were no changes in glucose or insulin levels in control subjects. An acute bout of resistance exercise was effective in improving integrated glucose concentration, including reducing peak glucose concentrations in women with type 2 diabetes, but not age-matched controls. There were no significant changes in insulin concentrations for either group. Resistance exercise offers an alternative to aerobic exercise for improving glucose control in diabetic patients. To realize optimal glucose control benefits, individuals must follow a regular schedule that includes daily exercise.     

Differential regulation of insulin action and tumor necrosis factor alpha system activity by metformin

BACKGROUND: Tumor necrosis factor alpha has a key role in insulin resistance. We study the effects of metformin on glucose tolerance, insulin resistance, beta cell function, and soluble tumor necrosis factor receptor (sTNFR) levels. METHODS: We performed a double-blind, randomized metformin-placebo study. Twenty-three subjects with impaired glucose tolerance or impaired fasting glucose were studied. Oral glucose tolerance, homeostasis model assessment, and continuous infusion of glucose with model assessment tests were used to evaluate glucose tolerance, insulin sensitivity, and beta cell function, respectively. Soluble tumor necrosis factor receptor levels were measured before and after therapy. Repeated measures analysis of variance was used for statistical analysis. RESULTS: After 12-week treatment, fasting glucose (110.1 +/- 9.9 to 98.9 +/- 15.7 mg/dl, P < .001), fasting insulin (11.6 +/- 5.4 to 8.8 +/- 3.5 mU/L, P = .05), fasting C-peptide (2.5 +/- 0.7 to 1.8 +/- 0.5 ng/mL, P < .05), and achieved C-peptide (5.2 +/- 1.2 to 4.2 +/- 1 ng/mL, P < .05) levels decreased in the metformin group. In addition, there was an improvement in insulin sensitivity (37.4% +/- 15.2% to 50.4% +/- 23.2%, P < .05) with unchanged sTNFR1 (2.0 +/- 0.8 to 2.3 +/- 1.2 microg/L, P = NS) and sTNFR2 (4.8 +/- 1.7 to 4.4 +/- 1.2 microg/L, P = NS) levels. CONCLUSIONS: Metformin is able to reverse insulin resistance and hyperglycemia in high-risk subjects for type 2 diabetes mellitus independently of the effects on tumor necrosis factor alpha system activity.     

Influence of age on the thermic response to caffeine in women

The purpose of this study was to examine age-related differences in the magnitude of caffeine-induced thermogenesis and the relationship of aerobic fitness, body composition, and hormone and substrate concentrations to the thermic effect of caffeine in younger and older women. Using a placebo-controlled, double-blind study design, 10 older (50 to 67 years) and 10 younger (21 to 31 years) healthy women who were moderate consumers of caffeine (self-reported intake: younger, 139 +/- 152 mg/d; older, 204 +/- 101 mg/d, NS, mean +/- SD) were characterized for fasting plasma glucose, insulin, free fatty acid (FFA), and caffeine levels, energy expenditure, body composition, anthropometry, aerobic fitness, physical activity, and energy intake. Before and after placebo and caffeine ingestion (5 mg/kg fat-free mass [FFM]), the following variables were measured: fasting plasma glucose, insulin, FFA, and energy expenditure, plasma glucose, insulin, and FFA, and energy expenditure in response to placebo and caffeine ingestion. Caffeine ingestion resulted in similar increases in younger and older women for plasma caffeine (younger, 80 +/- 34 to 5,604 +/- 528 ng/mL, P < .01; older, 154 +/- 134 to 5,971 +/- 867 ng/mL, P < .01) and fatty acids (younger, 294 +/- 118 to 798 +/- 248 micromol/L, P < .01; older, 360 +/- 180 to 727 +/- 310 micromol/L, P < .01), whereas plasma insulin and glucose levels remained unchanged from baseline. Energy expenditure increased following caffeine ingestion in both groups (younger, 15.4%, 1.09 +/- 0.14 to 1.24 +/- 0.13 kcal/min, P < .05; older, 7.8%, 0.98 +/- 0.14 to 1.06 +/- 0.12 kcal/min, P < .05), although there was a blunted thermic response in the older versus younger women (older, 6.9 +/- 5 kcal/90 min; younger, 15.5 +/- 7 kcal/90 min, P < .05). In younger women, the thermic response to caffeine was positively correlated with the waist circumference (r = .70, P < .05) and body weight (r = .91; P < .01), whereas aerobic fitness (r = .77; P < .05) was the only significant correlate in older women. In conclusion, older and younger women increase energy expenditure significantly following caffeine ingestion, but older women have a blunted thermic response compared with younger women. Second, the thermic response to caffeine is positively associated with the body weight and waist circumference in younger women, whereas a positive association with aerobic fitness was observed in older women. Thus, the physiologic determinants of the thermic response to caffeine differ among women of different age groups.     

Metformin therapy increases insulin-stimulated release of D-chiro-inositol-containing inositolphosphoglycan mediator in women with polycystic ovary syndrome

Some actions of insulin are mediated by putative inositolphosphoglycan mediators, and a deficiency in D-chiro-inositol-containing inositolphosphoglycan (DCI-IPG) may contribute to insulin resistance in women with polycystic ovary syndrome (PCOS). Furthermore, similar effects of DCI and metformin, an insulin-sensitizing drug, have been demonstrated in PCOS women. To determine whether metformin improves insulin actions by increasing biologically active DCI-IPG in women with PCOS, we analyzed DCI-IPG during an oral glucose tolerance test in 19 obese women with PCOS before and after 4-8 wk of metformin or placebo. After treatment, the mean (+/-SE) area under the curve (AUC) during the oral glucose tolerance test of insulin (AUC(insulin)) decreased significantly more in the metformin group, compared with the placebo group [-3574 +/- 962 vs. +1367 +/- 1021 micro IU/min.ml (-26 +/- 7 vs. +10 +/- 7 nmol/min.liter), P = 0.003], but the AUC of DCI-IPG (AUC(DCI-IPG)) decreased similarly in both groups (-1452 +/- 968 vs. -2207 +/- 1021%/min, P = 0.60). However, the ratio of AUC(DCI-IPG)/AUC(insulin) increased by 160% after metformin and decreased by 29% after placebo (P = 0.002 between groups). Moreover, metformin seemed to improve the positive correlation between AUC(DCI-IPG) and AUC(insulin) but not placebo (r = 0.32, P = 0.68 at baseline; r = 0.52, P = 0.12 after metformin; and r = -0.39, P = 0.30 after placebo). We conclude that in obese women with PCOS, metformin may improve the action of insulin in part by improving insulin-mediated release of DCI-IPG mediators, as evidenced by increased bioactive DCI-IPG released per unit of insulin.