Influence of Total vs. Visceral Fat on Insulin Action and Secretion in African American and White Children

Objective: To examine whether total body fat (FAT) in general or visceral fat (VFAT) in particular is associated with greater metabolic risk in white and African American children. Research Methods and Procedures: A total of 68 white and 51 African American children had measures of insulin sensitivity (Si) and acute insulin response (AIR) by a frequently sampled intravenous glucose tolerance test, total body fat by DXA and abdominal fat distribution (visceral vs. subcutaneous) by computed tomography. The influence of FAT and VFAT on insulin parameters were examined by comparing subgroups of children with high or low FAT vs. high or low VFAT and by multiple regression analysis. Results: In whites, fasting insulin, Si, and AIR were significantly influenced by FAT, but not VFAT (e.g., for Si, 9.8 ± 0.8 in low FAT vs. 4.6 ± 0.7 × 10^?4/min/[μIU/mL] in high FAT, p < 0.05; 6.8 ± 0.7 in low VFAT vs. 7.5 ± 0.8 × 10^?4/min/[μIU/mL] in high VFAT, p > 0.1). In African Americans, fasting insulin and Si were also primarily influenced by FAT (e.g., for Si, 4.9 ± 0.4 in low FAT vs. 2.8 ± 0.5 × 10^?4/min/[μIU/mL] in high FAT, p < 0.05) but not by VFAT, and there were no significant effects of either fat compartment on AIR. In multiple regression analysis, Si was significantly influenced by FAT (negative effect), ethnicity (lower in African Americans), and gender (lower in females), whereas fasting insulin was significantly influenced by VFAT (positive effect), ethnicity (higher in African Americans), and fat free mass (positive effect). Discussion: Body fat in general is the predominant factor influencing Si, but VFAT may have additional effects on fasting insulin. The lack of major effects of VFAT on Si in children may be explained by lower levels of VFAT or because VFAT affects aspects of whole body insulin action that are not measured by the minimal model.     

Ethnic Differences in the Responsiveness of Adipocyte Lipolytic Activity to Insulin

Objective: The goal of this study was to quantify differences in lipid metabolism and insulin sensitivity in black and white subjects to explain ethnic clinicopathological differences in type 2 diabetes. Research Methods and Procedures: The in vitro lipolytic activity of adipocytes isolated from obese black and white women was measured in the presence of insulin and isoproterenol. Insulin resistance was assessed in vivo using the euglycemic hyperinsulinemic clamp technique. Results: Fasting plasma levels of insulin and nonesterified fatty acid (NEFA) in black and white women were 67 ± 5 pM vs. 152 ± 20 pM (p < 0.01) and 863 ± 93 μM vs. 412 ± 34 μM (p < 0.01), respectively. Euglycemic hyperinsulinemic clamp studies showed that obese black subjects were more insulin‐resistant than their white counterparts (glucose infusion rates: 1.3 ± 0.2 vs. 2.2 ± 0.3 mg/kg per min; p < 0.05). Isolated adipocytes from white women were more responsive to insulin than those from black women with 0.7 nM insulin causing a 55 ± 4% inhibition of isoproterenol‐stimulated lipolysis compared with 27 ± 10% in black women (p < 0.05). Discussion: The low responsiveness of adipocyte lipolytic activity to insulin in black women in the presence of a relative insulinopenia may account for the high plasma NEFA levels seen in these women, which may, in turn, account for their higher in vivo insulin resistance. High NEFA levels may also contribute to the low insulin secretory activity observed in the obese black females. These data suggest that the pathogenesis of insulin resistance and type 2 diabetes within the black obese community is strongly influenced by their adipocyte metabolism.     

Serum zinc in highly trained adolescent gymnasts

Serum zinc was measured in 20 adolescent gymnasts (9 boys, 11 girls, age 12–15 yr) explored for detecting possible adverse effects of intense training on pubertal maturation and growth. They had low serum zinc (0.599±0.026 mg/L) when compared to matched control sedentary children (n=118 mean 0.81±0.014p<0.001). Girls had lower zinc than boys (0.557±0.023 vs 0.651±0.044p<0.001). Zinc was correlated to isometric adductor strength (r=0.468p<0.05). Children with serum zinc <0.6 mg/L had lower insulin-like growth factor binding protein 3 than others (2.326±0.264 vs 2.699±0.12p<0.01). Thus, zinc is lowered in trained adolescent gymnasts and even lower in females. This reduction could play some role in abnormalities of puberty, growth, or muscular performance.     

Relationship of Leptin Concentration to Gender,Menopause, Age,Diabetes, and Fat Mass in African Americans

This investigation was designed to determine the relationship of leptin concentration to gender, sex hormones, menopause, age, diabetes, and fat mass in African Americans. Participants included 101 African Americans, 38 men (mean age, 34. 2 ± 7. 4 years), 29 age-matched premenopausal women (mean age, 32. 6 ± 3. 7 years), and 36 postmenopausal women (mean age, 57. 8 ± 5. 9 years). The women were not taking exogenous sex hormones, and 12 subjects were diabetic. Percent body fat was calculated with the Siri formula, fat mass (FM) was calculated as weight x percent body fat, and Fat-free mass (FFM) was calculated as weight minus FM. Fasting plasma was assayed for leptin, estradiol, free testosterone, glucose, and insulin concentrations. The nondiabetics had an oral glucose tolerance test (OGTT). The diabetics compared with the non-diabetics had a higher central fat index (^P=0. 04) but otherwise were similar to nondiabetics in all parameters measured. Body mass index, percent body fat, and FM were greater in women than men (p<0. 001). Leptin concentrations in men, premenopausal, and postmenopausal women were: 7. 51 ± 8. 5, 33. 9 ± 17. 3, 31. 4 ± 22. 3 ng/mL. Leptin/FM x 100 in the three groups were: 28. 9 ± 16. 1, 98. 65 ± 44. 9, 77. 1 ± 44. 5 ng/mL/kg. The gender difference in leptin concentration and leptin/FM was significant (p<0. 001), but the difference between premenopausal and postmenopausal women was not. In each group, weight, percent body fat, and FM were highly correlated with leptin concentration. Multiple regression analyses with leptin concentration as the dependent variable and age, diabetic status, percent body fat, weight, FM, FFM, estradiol, and free testosterone concentrations as independent variables demonstrated that the determinants of leptin concentration in men was weight only (R=0. 83,p<0. 001), in premenopausal women it was FM only (R=0. 57,P<0. 001), and in postmenopausal women it was weight only (R=0. 67, p<0. 001). With diabetics excluded, the multiple regression analysis was repeated with fasting insulin concentration and the area under the insulin curve during the OGTT included as independent variables. The results for this multiple regression analyses were the same as the first. Therefore, leptin concentration in African Americans is determined by gender and fat mass. Menopause, age, and diabetes do not affect leptin concentration.     

Both Subcutaneous and Visceral Adipose Tissue Correlate Highly with Insulin Resistance in African Americans

Objective: The contribution of visceral adipose tissue (VAT) to insulin resistance is well‐established; however, the role of subcutaneous abdominal adipose tissue (SAT) in insulin resistance remains controversial. Sex may determine which of these two components of abdominal obesity is more strongly related to insulin resistance and its consequences. The aim of this study was to determine whether both VAT and SAT contribute to insulin resistance in African Americans and to examine the effects of sex on this relationship. Research Methods and Procedures: This was a cross‐sectional study of 78 nondiabetic African‐American volunteers (44 men, 35 women; age 33.8 ± 7.3 years; BMI 30.9 ± 7.4 kg/m²). VAT and SAT volumes were measured using serial computerized tomography slices from the dome of the diaphragm to the iliac crest. The insulin sensitivity index (S_I) was determined from the minimal model using data obtained from the frequently sampled intravenous glucose tolerance test. Results: In men, both VAT and SAT were negatively correlated with S_I (r for both correlations = ?0.57; p < 0.01). In women, the correlation coefficient between VAT and S_I was ?0.50 (p < 0.01) and between SAT and S_I was ?0.67 (p < 0.01). In women, the correlation coefficient for S_I with SAT was significantly greater than the correlation coefficient with VAT (p = 0.02). Discussion: Both SAT and VAT are strongly correlated with insulin resistance in African Americans. For African‐American women, SAT may have a greater effect than VAT on insulin resistance.     

Role of Insulin and Free Fatty Acids in the Regulation of ob Gene Expression and Plasma Leptin in Normal Rats

Objective: It is under debate whether free fatty acids (FFAs) play an independent role in the regulation of adipose cell functions. In this study, we evaluated whether leptin secretion induced by FFA is due directly to an increased FFA availability or whether it is mediated by insulin levels. Research Methods and Procedures: To test this hypothesis, we compared the effects of six different experimental designs, with different FFA and insulin levels, on plasma leptin: euglycemic clamp, euglycemic clamp + FFA infusion, FFA infusion alone, FFA + somatostatin infusion, somatostatin infusion alone, and saline infusion. Results: Our results showed that euglycemic clamp, FFA infusion, or both in combination induced a similar increment of circulating leptin (3.31 ± 0.30, 3.40 ± 0.90, and 3.35 ± 0.80 ng/mL, respectively). Moreover, the inhibition of FFA‐induced insulin increase by means of somatostatin infusion completely abolished the rise of leptin in response to FFA (1.05 ± 0.30 vs. 3.40 ± 0.90 ng/mL, p < 0.001). Discussion: In conclusion, our data showed that the effects of high FFA levels on plasma leptin were mediated by the rise of insulin concentration. These data confirm a major role for insulin in the regulation of leptin secretion from rat adipose tissue and support the hypothesis that leptin secretion is coupled to net triglyceride synthesis in adipose tissue.     

Visceral Fat Accumulation as a Risk Factor for Prostate Cancer

Objective: No clear association between obesity or body fat distribution and prostate cancer has been shown. We investigated the relation between visceral fat accumulation as measured by computed tomography (CT) and the occurrence of prostate cancer. Research Methods and Procedures: We compared body fat distribution assessed by a direct method (CT) in 63 prostate cancer cases with 63 age‐matched healthy community controls. A CT scan at the level of the fourth lumbar vertebra was performed in all participants. Results: Patients presented a significantly higher mean total abdominal fat area (509.2 ± 226.1 vs. 334.3 ± 132.9 cm², p < 0.001), mostly because of a higher mean visceral fat area (VF; 324.7 ± 145.6 vs. 177.4 ± 88.4 cm², p < 0.001) and a significantly higher mean ratio between visceral and subcutaneous fat areas (V/S ratio; 1.8 ± 0.4 vs. 1.2 ± 0.4, p < 0.001). A significantly higher risk of prostate cancer was found for participants with higher VF (odds ratio = 4.6; 95% confidence interval = 2.6 to 8.2 per SD increase) and V/S ratio (odds ratio = 6.0; 95% confidence interval = 2.3 to 11.0 per SD increase). Discussion: These results suggest a role for visceral obesity, quantified by CT, as a risk factor for prostate cancer. The action of the adipocytokines secreted by visceral fat cells, steroid hormone disturbances, and increased levels of insulin or other hormones noted in visceral obesity may explain this association.     

Modest Lifestyle Intervention and Glucose Tolerance in Obese African Americans

Objective: Previous studies have demonstrated the benefit of short‐term diets on glucose tolerance in obese individuals. The purpose of this study was to evaluate the effectiveness of modest lifestyle changes in maintaining improvements in glucose tolerance induced by short‐term energy restriction in obese African Americans with impaired glucose tolerance or type 2 diabetes mellitus. Research Methods and Procedures: An intervention group (n = 45; 47 ± 1 year [mean ± SE]), 105 ± 4 kg; body mass index: 39 ± 1 kg/m²) received an energy‐restricted diet (943 ± 26 kcal/d) for 1 week, followed by a lifestyle program of reduced dietary fat (?125 kcal/d) and increased physical activity (+125 kcal/d) for 1 year. Body weight and plasma concentrations of glucose, insulin, and C‐peptide during an oral glucose tolerance test were measured at baseline, 1‐week, and 4‐month intervals. A control group (n = 24; 48 ± 1 year; 110 ± 5 kg; body mass index: 41 ± 2 kg/m²) underwent these measurements at 4‐month intervals. Results: No changes in weight or glucose tolerance were observed in the control group. The intervention group had significant (p < 0.05) improvements in body weight and glucose tolerance in response to the 1‐week diet, which persisted for 4 months (p < 0.001 vs. control for change in weight). A total of 19 subjects (42%) continued the intervention program for 1 year, with sustained improvements (weight: ?4.6 ± 1.0 kg; p < 0.001 vs. control; oral glucose tolerance test glucose area: ?103 ± 44 mM · min; p < 0.05 vs. control). Discussion: A modest lifestyle program facilitates weight loss and enables improvements in glucose tolerance to be maintained in obese individuals with abnormal glucose tolerance. However, attrition was high, despite the mild nature of the program.     

Plasma Leptin Response to an Epinephrine Infusion in Lean and Obese Women

Objective: Because leptin production by adipose tissue is under hormonal control, we examined the impact of epinephrine administration on plasma leptin concentrations. Research Methods and Procedures: We measured plasma leptin, insulin, and free fatty acid (FFA) responses after a 60-minute epinephrine infusion (0.010 μg/kg fat free mass/min) followed by a 30-minute recovery period (no infusion) in a group of 11 lean (mean body mass index ± SD: 22.6 ± 1.1 kg/m²) and 15 obese (30.0 ± 1.3 kg/m²) premenopausal women. Leptin, insulin, and FFA levels were measured in plasma before (−15 and 0 minutes) and at every 30 minutes over the 90-minute period. Results: In both lean and obese individuals, plasma leptin was significantly reduced by epinephrine (p < 0.0001). Body fat mass was associated with fasting leptin levels (r = 0.64, p < 0.0005) as well as with the decrease in leptinemia (r = −0.51, p < 0.01) produced by epinephrine administration. Furthermore, we noted a large range of leptin response to epinephrine among our subjects, especially in obese women (from −12 to −570 ng/mL per 60 minutes). However, there was no association between postepinephrine leptin and FFA levels (r = −0.14, p = 0.55). Discussion: Results of this study indicate that leptin levels decrease after epinephrine administration in both lean and obese premenopausal women. However, the heterogeneity in the response of leptin to catecholamines suggests potential alterations of the leptin axis that may contribute to generate a positive energy balance and, thus, may favor weight gain in some obese individuals.     

Liver-Fat Accumulation and Insulin Resistance in Obese Women with Previous Gestational Diabetes

Objective: We determined whether fat accumulation in the liver is associated with features of insulin resistance independent of obesity. Research Methods and Procedures: We recruited 27 obese nondiabetic women in whom liver fat (LFAT) content was determined by proton spectroscopy, intra-abdominal and subcutaneous fat by magnetic resonance imaging, and insulin sensitivity by the euglycemic insulin clamp technique. The women were divided based on their median LFAT content (5%) to groups with low (3.2 ± 0.3%) and high (9.8 ± 1.5%) liver fat. The groups were almost identical with respect to age (36 ± 1 vs. 38 ± 1 years in low vs. high-LFAT), body mass index (32.2 ± 0.6 vs. 32.8 ± 0.5 kg/m²), waist-to-hip ratio, intra-abdominal, subcutaneous, and total fat content. Results: Women with high LFAT had features of insulin resistance including higher fasting serum triglyceride (1.93 ± 0.21 vs. 1.11 ± 0.09 mM, p < 0.01) and insulin (14 ± 3 vs. 10 ± 1 mU/L, p < 0.05) concentrations than women with low LFAT. The group with high LFAT also had higher 24-hour blood pressures, and lower whole-body insulin sensitivity compared with the low-LFAT group. Discussion: In obese women with previous gestational diabetes, LFAT, rather than any measure of body composition, is associated with features of insulin resistance.     

Effects of diabetes type and treatment on zinc status in diabetes mellitus

Zinc status was assessed in 53 diabetic patients: 18 insulin-dependent diabetic patients (IDDM), 22 noninsulin-dependent diabetic patients (NIDDM) treated with oral antidiabetic agents, and 13 insulin-treated, noninsulin-dependent diabetic patients (IRDM). Plasma zinc concentrations were in the usual range for healthy subjects in these three groups (15.3±0.9 μmol/L). Urinary zinc excretions were elevated in the IDDM group (18.3±4.1 μmol/24 h;p<0.01 vs normal) and in the NIDDM group (17.5±3.5 μmol/24 h;p<0.01 vs normal), but normal in the IRDM group (11.3±2.4 μmol/24 h). In 14 NIDDM patients treated with transient continuous sc insulin injections, urinary zinc decreased from 16.5±2.2 μmol/24 h before insulin treatment to 11.5±0.3 μmol/24 h after insulin treatment without any modification in plasma zinc concentrations.     

Metabolic Response to a Mixed Meal in Obese and Lean Women from Two South African Populations

Objective: Lower lipid and insulin levels are found during a glucose-tolerance test in obese black than obese white South African women. Therefore, β-cell function and lipid metabolism were compared in these populations during a mixed meal. Research Methods and Procedures: Blood concentrations of glucose, free fatty acids (FFAs), insulin, lipograms, and in vivo FFA oxidation were determined at fasting and for 7 hours after oral administration of a mixed emulsion containing glucose-casein-sucrose-lipid and [1-¹³C] palmitic acid in 8 lean black women (LBW), 10 obese black women (OBW), 9 lean white women (LWW), and 10 obese white women (OWW). Subcutaneous and visceral fat mass was assessed by computerized tomography. Results: Visceral fat area was higher in OWW (152.7 ± 17.0 cm²) than OBW (80.0 ± 6.7 cm²; p < 0.01). In OBW, 30-minute insulin levels were higher (604.3 ± 117.6 pM) than OWW (311.0 ± 42.9 pM; p < 0.05). Total triglyceride was higher in OWW (706.7 ± 96.0 mM × 7 hours) than OBW (465.7 ± 48.2 mM × 7 hours; p < 0.05) and correlated with visceral fat area (β = 0.38, p = 0.05). Palmitate oxidation was higher in lean than obese women in both ethnic groups and correlated negatively with fat mass (β = −0.58, p < 0.005). Discussion: The higher 30-minute insulin response in OBW may reflect a higher insulinotropic effect of FFAs or glucose. The elevated triglyceride level of OWW may be due to their higher visceral fat mass and possibly reduced clearance by adipose tissue.     

Selenium Levels in First-Degree Relatives of Diabetic Patients

The present study was conducted to evaluate the serum selenium levels in first-degree relatives of diabetic patients (FDR) according to controls. Insulin resistance, serum lipid levels, inflammation markers, and blood pressure were also studied in these patients. Serum levels of selenium in FDR were significantly lower than control group (74.65 ± 5.9 vs 88.7 ± 8.7 μg/dl, p < 0.0001). HsCRP, HOMA-IR, insulin, homocysteine levels were significantly higher in FDR according to the control group (1.32 ± 0.9 vs 0.63 ± 0.4 mg/dL, p < 0.0001; 2.07 ± 0.84 vs 1.51 ± 0.69, p < 0.0001; 9.26 ± 3.8 vs 6.8 ± 2.98 μU/MI, p < 0.0001; 15.7 ± 7.4 vs 11.5 ± 5.1 μmol/L, p < 0.0001, respectively). There was significant correlation between selenium levels and hsCRP (r = − 0.450, p < 0.0001). There was also weak significant correlation also between HOMA-IR and selenium levels (r = −0.227, p = 0.003). There was a correlation between systolic blood pressure and BMI (r = 0.365, p < 0.0001). But there was no correlation between selenium levels and blood pressure or other parameters. HsCRP, HOMA-IR, homocysteine levels in individuals with selenium levels < 80 μg/L (n = 78) was significantly higher than hsCRP HOMA-IR, homocysteine levels in individuals with selenium levels ≥ 80 (n = 91; 1.23 ± 0.98 vs 0.81 ± 0.76 mg/dL, p < 0.003; 1.99 ± 0.88 vs 1.64 ± 0.74, p < 0.005; 15.0 ± 7.6 vs 12.9 ± 5.7 μmol/L, p < 0.049, respectively). Selenium deficiency may contribute to cardiovascular disease risk in FDR.     

The Effect of Dietary Energy Restriction on Body Weight Gain and the Development of Noninsulin-Dependent Diabetes Mellitus (NIDDM) in Psammomys obesus

Food intake was restricted to 75% of ad libitum levels in 37 male Psammomys obesus (Israeli Sand Rats) from the ages of 4 (weaning) to 10 weeks. Energy restriction reduced the mean body weight at 10 weeks by 29% compared with 44 ad libitum fed controls. Hyperglycemia was prevented completely in the food-restricted group, and mean blood glucose concentrations were significantly reduced (3.8 ± 0.2 vs. 5.5 ± 0.4 μmol/L; p<0.05) compared with control animals. Plasma insulin concentrations were also decreased significantly compared with ad libitum fed controls (105 ± 13 vs. 241 ± 29 mU/L;p<0.05). Although energy restriction prevented hyperglycemia from developing in 10-week-old P. obesus, 19% of the food restricted animals still developed hyperinsu-linemia. We concluded that hyperphagia between the ages of 4 to 10 weeks may be essential for the development of noninsulin-dependent diabetes mellitus in P. obesus, but that hyperinsulinemia may still occur in the absence of hyperphagia and hyperglycemia, suggesting a significant genetic influence on the development of hyperinsulinemia in this animal model.     

Reduction of Plasma Leptin Concentrations by Arginine but Not Lipid Infusion in Humans

Objective: We examined short-term effects of arginine infusion on plasma leptin in diabetic and healthy subjects. Research Methods and Procedures: Arginine stimulation tests were performed in C-peptide negative type 1 [DM1; hemoglobin A_1c; 7.3 ± 0.3%], hyperinsulinemic type 2 diabetic (DM2; 7.6 ± 0.7%), and nondiabetic subjects (CON; 5.4 ± 0.1%). Results: Fasting plasma leptin correlated linearly with body mass index among all groups (r = 0.61, p = 0.001). During arginine infusion, peak plasma insulin was lower in DM1 than in DM2 (p < 0.05) and CON (p < 0.01). Plasma leptin decreased within 30 minutes by ∼11% in DM1 (p < 0.001), DM2 (p < 0.01), and CON (p < 0.005), slowly returning to baseline thereafter. Plasma free fatty acids (FFAs) were higher in DM1 (0.6 ± 0.1 mM) and DM2 (0.6 ± 0.1 mM) than in CON (0.4 ± 0.1 mM, p < 0.05) and transiently declined by ∼50% (p < 0.05) at 45 minutes in all groups before rebounding toward baseline. To examine the direct effects of FFAs on plasma leptin, we infused healthy subjects with lipid/heparin and glycerol during fasting, and somatostatin-insulin (∼35 pM) -glucagon (∼90 ng/mL) clamps were performed. In both protocols, plasma leptin continuously declined by ∼25% (p < 0.05) during 540 minutes without any difference between the high and low FFA conditions. Discussion: Arginine infusion transiently decreased plasma leptin concentrations both in insulin-deficient and hyperinsulinemic diabetic patients, indicating a direct inhibitory effect of the amino acid but not of insulin or FFAs.     

Insulin Resistance in Nondiabetic Morbidly Obese Patients: Effect of Bariatric Surgery

Objective: To evaluate insulin action on substrate use and insulinemia in nondiabetic class III obese patients before and after weight loss induced by bariatric surgery. Research Methods and Procedures: Thirteen obese patients (four men/nine women; BMI = 56.3 ± 2.7 kg/m²) and 13 lean subjects (five men/eight women; BMI = 22.4 ± 0.5 kg/m²) underwent euglycemic clamp, oral glucose tolerance test, and indirect calorimetry. The study was carried out before (Study I) and after (～40% relative to initial body weight; Study II) weight loss induced by Roux‐en‐Y Gastric bypass with silastic ring surgery. Results: The obese patients were insulin resistant (whole‐body glucose use = 19.7 ± 1.5 vs. 51.5 ± 2.4 μmol/min per kilogram fat‐free mass, p < 0.0001) and hyperinsulinemic in the fasting state (332 ± 86 vs. 85 ± 5 pM, p < 0.0001) and during the oral glucose tolerance test compared with the lean subjects. Fasting plasma insulin normalized after weight loss, whereas whole‐body glucose use increased (35.5 ± 3.7 μmol/min per kilogram fat‐free mass, p < 0.05 vs. Study I). The higher insulin clearance of obese did not change during the follow‐up period. Insulin‐induced glucose oxidation and nonoxidative glucose disposal were lower in the obese compared with the lean group (all p < 0.05). In Study II, the former increased slightly, whereas nonoxidative glucose disposal reached values similar to those of the control group. Fasting lipid oxidation was higher in the obese than in the control group and did not change significantly in Study II. The insulin effect on lipid oxidation was slightly improved (p = 0.01 vs. Study I). Discussion: The rapid weight loss after surgery in obese class III patients normalized insulinemia and improved insulin sensitivity almost entirely due to glucose storage, whereas fasting lipid oxidation remained high.     

Intermittent hypoxia maintains glycemia in streptozotocin-induced diabetic rats

Increasing studies have shown protective effects of intermittent hypoxia on brain injury and heart ischemia. However, the effect of intermittent hypoxia on blood glucose metabolism, especially in diabetic conditions, is rarely observed. The aim of this study was to investigate whether intermittent hypoxia influences blood glucose metabolism in type 1 diabetic rats. Streptozotocin-induced diabetic adult rats and age-matched control rats were treated with intermittent hypoxia (at an altitude of 3 km, 4 h per day for 3 weeks) or normoxia as control. Fasting blood glucose, body weight, plasma fructosamine, plasma insulin, homeostasis model assessment of insulin resistance (HOMA-IR), pancreas β-cell mass, and hepatic and soleus glycogen were measured. Compared with diabetic rats before treatment, the level of fasting blood glucose in diabetic rats after normoxic treatment was increased (19.88?±?5.69 mmol/L vs. 14.79?±?5.84 mmol/L, p?<?0.05), while it was not different in diabetic rats after hypoxic treatment (13.14?±?5.77 mmol/L vs. 14.79?±?5.84 mmol/L, p?>?0.05). Meanwhile, fasting blood glucose in diabetic rats after hypoxic treatment was also lower than that in diabetic rats after normoxic treatment (13.14 ± 5.77 mmol/L vs. 19.88 ± 5.69 mmol/L, p<0.05). Plasma fructosamine in diabetic rats receiving intermittent hypoxia was significantly lower than that in diabetic rats receiving normoxia (1.28?±?0.11 vs. 1.39?±?0.11, p?<?0.05), while there were no significant changes in body weight, plasma insulin and β-cell mass. HOMA-IR in diabetic rats after hypoxic treatment was also lower compared with diabetic rats after normoxic treatment (3.48?±?0.48 vs. 3.86?±?0.42, p?<?0.05). Moreover, intermittent hypoxia showed effect on the increase of soleus glycogen but not hepatic glycogen. We conclude that intermittent hypoxia maintains glycemia in streptozotocin-induced diabetic rats and its regulation on muscular glycogenesis may play a role in the underlying mechanism.     

Body Composition Changes in Caucasian and African American Children and Adolescents with Obesity Using Dual-Energy X-ray Absorptiometry Measurements after a 10-Week Weight Loss Program

Objective : Changes in body composition during a weight loss program have not been described in children. We wanted to test the hypothesis that weight loss can be achieved while maintaining total body fat-free mass. Research Methods and Procedures : We determined body composition changes by using dual-energy X-ray absorptiometry measured at baseline and after the first 10 weeks of a multidisciphnary weight loss program. The program consisted of 10 weekly group sessions where the children were provided instruction in lifestyle modification, including diet and exercise. Program leaders included a pediatrician, psychologist, registered dietitian, and exercise instructor. Results : We studied 59 obese children, mean (± SD) age 12.8 ± 2.6 years, 29% boys and 71% girls, 49% Caucasian, and 51% African American. At enrollment, the children's mean height and body mass index were 157 cm and 38.9 kg/m², respectively. The children's dual-energy X-ray absorptiometry-derived mean at baseline and at 10 weeks and corresponding p values were: weight (94.6 kg vs. 92.3 kg, p<0.0001), total body fat mass (46.9 kg vs. 44.3 kg, p<0.0001), percentage total body fat (49.2% vs. 47.5%, p<0.0001), total trunk mass (43.0 kg vs. 41.5 kg,p<0.0001), total trunk fat (21.2 kg vs. 20.0 kg, p<0.0001), total body fat-free mass (47.6 kg vs. 47.9 kg, p = 0.33), total body bone mass (2.7 kg vs. 2.7 kg, p = 0.99), and total body bone mineral density (1.14 g/cm² vs. 1.15 g/cm², p = 0.0119). The children's race, gender, or Tanner stage did not affect these changes. Discussion : Decreases in total body fat mass was achieved, and total body fat-free mass was maintained among boy and girl Caucasian and African American children participating in this lifestyle modification weight loss program.     

Urinary zinc and its relationships with microalbuminuria in type I diabetics

We investigated whether zincuria is associated with microalbuminuria in type I (insulin-dependent) diabetics (IDDM). In 169 IDDM, 215 overnight urine samples were collected for simultaneous assay of zinc and albumin. In 76 samples with excessive microalbuminuria (>15 mg/L), zincuria was higher than in the 139 other samples (0.83±0.06 vs 0.58±0.03 mg/Lp<0.001), though zincuria and microalbuminuria were not significantly correlated. An exercise provocation test was performed in 78 IDDM. Although microalbuminuria increased, zincuria did not change during the test. Another group of 83 IDDM underwent urinary zinc determination over a period of 1 h of recumbency. The 48 patients who had a zincuria higher than the mean+2 SD of control values had higher microalbuminuria at rest (48±16 μg/min vs 12±2p<0.01) and after exercise (111±33 vs 42±14p<0.02) than the remaining 35 subjects. Both subgroups did not differ for zinc intake and zincemia. Thus, incipient nephropathy as detected by the measurement of microalbuminuria is associated with a highly significant increase in zinc excretion, which is not proportional to albumin leakage, nor is it amplified during exercise. Hyperzincuria is not explained by an increase in zinc intake and does not result in hypozincemia.     

Muscle Type‐Dependent Responses to Insulin in Intramyocellular Triglyceride Turnover in Obese Rats

Objective: To understand the role of hyperinsulinemia in intramyocellular (imc) triglyceride (TG) accumulation and in regulating imcTG turnover. Research Methods and Procedures: imcTG was first prelabeled by continuous infusion of [U‐¹⁴C]glycerol (pulse), and then the rate of label loss from the prelabeled imcTG pool (turnover) in gastrocnemius, tibialis anterior, and soleus muscle of awake, high‐fat‐fed obese rats during the subsequent hyperinsulinemic‐euglycemic clamp experiments (chase) was determined. Results: Post‐absorptive basal fractional imcTG turnover rate in soleus was 0.010 ± 0.001/min, significantly lower than that in gastrocnemius (0.026 ± 0.002/min, p < 0.001) or tibialis anterior (0.030 ± 0.002/min, p < 0.0001), a pattern reciprocal to their imcTG pool size. Insulin infusion at 25 pmol/kg per minute resulted in pathophysiological hyperinsulinemia (5‐fold increase over the baseline value). This caused an increase in imcTG turnover by 3‐fold in soleus (0.029 ± 0.006/min, p = 0.002) but a decrease in gastrocnemius (0.012 ± 0.003/min, p = 0.001) and in tibialis anterior (0.0064 ± 0.001/min, p < 0.0001). Pathophysiological hyperinsulinemia suppressed hormone‐sensitive lipase activity in heart (p = 0.01) and mesenteric fat (p = 0.05) but not in skeletal muscle (p > 0.05). The pool size of imcTG was not affected by hyperinsulinemia. Discussion: The results demonstrated muscle‐type dependence in the response of imcTG turnover to hyperinsulinemia in the obesity model. The reciprocal insulin effects on imcTG turnover in oxidative vs. oxidative‐glycolytic muscle indicated a possibility that oxidative muscle contributes more to insulin resistance under hyperinsulinemia if imcTG‐fatty acid oxidation is a function of turnover. imcTG turnover does not seem to regulate imcTG pool size acutely.