Acute insulin administration does not affect plasma leptin levels in lean or obese subjects

Abstract. Whether leptin levels are related to insulin sensitivity or subject to acute regulation by insulin is not known. In 12 obese [body mass index (BMI) = 34.0 ±1.5 kg m^-2] and 12 lean (BMI = 22.2 ±0.6 kg m^-2) non-diabetic subjects, plasma leptin concentrations were measured in the fasting state and during 2 hours of euglycaemic hyperinsulinaemia (˜600 pmol L^-2). Fasting plasma leptin was significantly higher in obese (26.6 ±3.2) than in lean subjects (6.4 ±1.2 ng mL^-1, P = 0.0001), and in women (21.1 ±3.3) than in men (7.3 = 2.3 ng mL^-1, P = 0.01). In univariate analysis, fasting plasma leptin was strongly related to all anthropometric measures (body weight, fat mass, percent fat mass, waist and hip circumferences). In multiple regression, per cent adiposity, hip circumference and duration of obesity explained 90% of the variability in fasting leptin concentrations. Fasting and stimulated (OGTT) insulin levels, insulin sensitivity (22.6 ±1.9 vs 36.7 ±2.0 μmol min^-1 kg^-1 in lean and obese subjects, respectively, P < 0.0001), glucose area, and serum triglycerides were positively related to fasting plasma leptin concentrations; none of these associations, however, was statistically significant after adjusting for BMI. During the clamp, plasma leptin concentrations remained constant in both lean and obese subjects. We conclude that neither insulin levels nor sensitivity relate to leptin levels independently of fat mass, and that leptin is not subject to acute (2 hours) regulation by insulin in lean or obese humans.     

The glucoregulatory and antilipolytic actions of insulin in abdominal obesity with normal or impaired glucose tolerance: an in vivo and in vitro study

To evaluate the effects of obesity and impaired glucose tolerance on insulin sensitivity, we performed a euglycaemic-hyperinsulinemic clamp at about 350 pmol l-1, combined with 3H-glucose infusion, in 14 obese patients, BMI 36.5 +/- 1.2 and in 12 matched controls, BMI 23.9 +/- 0.4. Six obese patients had normal glucose tolerance (oNGT), and eight had impaired glucose tolerance (oIGT). The ability of insulin to inhibit lipolysis in isolated adipocytes was also studied. Insulin-mediated glucose utilization was more severely impaired in oIGT than in oNGT with respect to the controls (621 +/- 51 vs. 897 +/- 83 vs. 1298 +/- 55 mumol m-2 min-1, P < 0.001). Plasma glycerol was higher in oIGT than in oNGT and in the controls, both fasting (238 +/- 12 vs. 179 +/- 14 vs. 112 +/- 8 mumol l-1, P < 0.001) and during the clamp (175 +/- 21 vs. 120 +/- 12 vs. 36 +/- 6 mumol l-1, P < 0.001). The correlation between glucose utilization and the percent reduction of plasma glycerol during the clamp was significant in the study group as a whole (r = 0.809, P = 0.0001), and in each of the groups separately (oIGT: r = 0.929, P = 0.002; oNGT: r = 0.943, P = 0.036; controls: r = 0.902, P = 0.0001). Inhibition by insulin of noradrenaline-stimulated lipolysis in isolated adipocytes was more severely impaired in oIGT than in oNGT compared with the controls (P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Regional fat mass by DXA: High leg fat mass attenuates the relative risk of insulin resistance and dyslipidaemia in obese but not in overweight postmenopausal women

Objective. To investigate the influence of regional fat mass (FM) on insulin resistance and dyslipidaemia in obese postmenopausal women (BMI >30?kg/m²) compared to overweight women (BMI <30?kg/m²). Leg FM may attenuate the increased risk of cardiovascular disease and diabetes imposed by increased trunk FM in normal and overweight postmenopausal women. Material and methods. Cross‐sectional and consecutively referred patients comprising 63 obese and 36 overweight postmenopausal women. Body composition and regional FM by dual X‐ray absorptiometry (DXA), fasting glucose, fasting insulin and C‐peptide, insulin resistance by homeostasis model assessment (HOMA‐IR), insulin sensitivity by quantitative insulin sensitivity check index (QUICKI) and metabolic clearance rate (MCRestOGTT), insulin secretion (HOMAsecr) and serum lipids were assessed. Results. In obese subjects, leg FM was favourably associated with HOMA‐IR (p<0.05), QUICKI (p<0.05), fasting glucose (p<0.05), fasting insulin (p<0.05), HOMAsecr (p<0.05) and total cholesterol/HDL ratio (p<0.05). Trunk FM was unfavourably associated with MCRestOGTT (p<0.01), QUICKI (p<0.05) and fasting insulin (p<0.05). Compared to leg FM, leg/trunk FM ratio was more strongly associated with fasting insulin (p<0.001), fasting C‐peptide (p<0.001), HOMA‐IR (p<0.001), MCRestOGTT (p<0.001), QUICKI (p<0.001), HOMAsecr (p<0.001), fasting glucose (p<0.01) and triglycerides (p<0.01). Stepwise multiple regression demonstrated that leg/trunk FM ratio was the most important variable with partial R² = 0.26 (p<0.001) for HOMA and R² = 0.37 (p<0.001) when QUICKI was used as the dependent variable. In overweight women, no associations between fat mass and parameters of insulin resistance or dyslipidaemia were found. Conclusions. A high leg/trunk FM ratio as measured by DXA may give relative protection against diabetes and cardiovascular disease in obese postmenopausal women, but not in overweight women.     

腹型肥胖人群中不同糖代谢水平者胰岛素抵抗及胰岛分泌功能的探讨

目的 探讨腹型肥胖人群中不同糖代谢水平者胰岛素抵抗及胰岛分泌功能的状态。方法 腹型肥胖患者共382例，其中正常糖耐量(NGT)组251例，空腹血糖异常(IFG)组40例，异常糖耐量(IGT)组41例，2型糖尿病(DM组)50例。测腰围、血压、空腹血脂、血糖及血浆胰岛素，应用稳态模式胰岛素抵抗指数(HOMA-IR)作为胰岛素抵抗指标，稳态模式胰岛B细胞功能指数(HBCI)作为胰岛素分泌指标。结果 在腹型肥胖的人群中，不同糖代谢组的HOMA-IR差异具有统计学意义，从NGT→IFG／IGT→DM组HOMA-IR逐渐升高，而HBCI在各组内变化较大，数值分布较分散，与NGT、IFG、IGT组相比，DM组的HBCI明显下降，差别有统计学意义。同时收缩压随着糖代谢的恶化从NGT、IGT IFG到DM组逐步升高，舒张压的变化无明显的规律。结论 腹型肥胖人群中，从NGT经IFG／IGT向2型糖尿病发展的过程中，胰岛素敏感性逐渐下降，β细胞胰岛素分泌功能明显下降是出现DM的主要原因。这一结果与其他种族中的研究结果不完全相同，提示即使是肥胖相关的2型糖尿病，种族、遗传因素仍然在糖尿病发展过程中发挥着重要作用。     

肥胖糖尿病患者腹内脂肪含量与脂肪细胞因子、胰岛素抵抗相关性研究

目的探讨肥胖2型糖尿病患者腹内脂肪含量与脂肪细胞因子、胰岛素抵抗的关系。方法分别检测36名肥胖2型糖尿病患者和20名正常体质量糖尿病患者的腹内脂肪含量、血清脂肪细胞因子(TNF-α、IL-6、瘦素、脂联素)水平及空腹血糖、空腹胰岛素等指标。结果与对照组相比,肥胖组的腹内脂肪含量Homa-IR、TNF-α、IL-6、瘦素显著升高,而脂联素显著降低(P0.05)。肥胖组患者的腹内脂肪含量与TNF-α、IL-6、瘦素水平正相关,与脂联素水平负相关(P0.05)。线性回归分析显示腹内脂肪含量是Homa-IR的独立影响因素。结论肥胖糖尿病患者腹内脂肪的积聚可加重胰岛素抵抗,其机制可能部分与腹内脂肪组织分泌的细胞因子有关。     

Regional differences and effect of weight reduction on human fat cell metabolism

Abstract. The metabolism of adipocytes from severely obese patients was investigated before and after weight was reduced by jejuno-ileal by-pass. After weight reduction lipolysis and glucose incorporation into triglycerides were decreased as was the cell size. The effect of submaximal concentrations of insulin on glucose incorporation increased with weight reduction implying increased cellular insulin sensitivity.
The rate of glucose incorporation and basal lipolysis in the adipocytes correlated directly with the fasting plasma insulin level before weight reduction. After weight reduction there was a positive correlation between the decrease in glucose metabolism and the reduction in the plasma insulin level. These data support the concept that plasma insulin may be important for the long-term regulation of glucose metabolism and lipolysis in fat cells.
In other patients with normal body weight, studies on regional differences in adipocyte metabolism showed that fat cells from the subcutaneous abdominal region responded better to both noradrenaline and insulin than femoral fat cells. The differences between these sites were less pronounced during incubation with isopropylnoradrenaline, suggesting there was increased α-receptor activity in the femoral region.
Adipocytes in the abdominal subcutaneous region are thus metabolically much more active than those in the femoral region. This might explain why several blood parameters such as arterial free fatty acid and glycerol levels correlate with lipolysis of abdominal but not femoral cells and why plasma insulin and triglyceride levels correlate with abdominal but not femoral fat cell size. Also, the responsiveness of adipocytes in the abdominal region may explain why cells in this region decreased more in size than those in the femoral region during weight reduction.     

Influence of family history of hypertension on insulin sensitivity in lean and obese hypertensive subjects

We evaluated the influence of family history of hypertension on insulin sensitivity in lean and obese hypertensive subjects (H): 40 lean [body mass index (BMI)  25 kg m⁻²] H with normotensive parents (F−), 50 lean H with one or two parents hypertensive (F+), 30 obese HF− (BMI  30 kg m⁻²) and 35 obese HF+. The four groups were comparable in terms of age, sex and ambulatory blood pressure values. We evaluated glucose, insulin and C-peptide before and 30, 60, 90 and 120 min after an oral glucose load, insulin sensitivity index (ISI, fasting glucose/insulin ratio), fasting insulin/C-peptide ratio (I/Cp). Glucose, fasting and during test, and I/Cp were similar among the four groups; insulin and C-peptide, fasting and stimulated, were significantly higher and ISI lower in obese H than in lean H; at similar BMI, insulin and C-peptide were significantly higher in F+ than in F−. Insulin directly correlated with night-time blood pressure only in lean HF−. The correlation between insulin and BMI was significantly closer in F− than in F+. In conclusion, family history of hypertension appears to play a relevant role in insulin sensitivity in hypertensive subjects also in the presence of obesity.     

Effect of regional fat loss assessed by DXA on insulin resistance and dyslipidaemia in obese women

Abstract

Objective. To investigate the impact of reduction in total fat mass (FM) and regional FMs on indices of insulin resistance and dyslipidaemia in obese women (BMI > 30 kg/m²) after a 1-year weight loss (WL) program; and, secondly, to investigate the potential predictive effect of baseline insulin resistance on reduction in total and regional FMs. Material and methods. In 35 women with > 4kg weight loss, body composition by DXA (dual X-ray absorptiometry), fasting insulin, C-Peptide, insulin resistance (HOMA-IR), insulin sensitivity (QUICKI), metabolic clearance rate (MCRestOGTT) and serum lipids were assessed. Results. Mean WL was 9.6%; trunk and leg FM were reduced proportionally (14.9–14.7%). Improvement in HOMA-IR was 34.7%, insulin 30.7%, QUICKI 8.6% and MCRest OGTT 74%. The reduction in total, trunk and leg FM were similarly correlated with improvement in indices of insulin resistance (p < 0.001–0.05) and also with initial HOMA-IR (p = 0.000–0.02). In linear regressions improvement in HOMA-IR was similarly related with these FMs (p = 0.008), and initial HOMA predicted loss of trunk FM (p = 0.01). In multivariate analysis improvement in HOMA-IR was explained by loss of total FM (R² = 0.20, p = 0.004); improvement of QUICKI by loss of leg FM (R² = 0.33, p < 0.001). Conclusion. Loss of leg FM and trunk FM had similar importance for the improvement in insulin resistance. Baseline HOMA-IR predicted the potential for reduction in trunk FM.     

男性腹型肥胖患者腹部脂肪面积与胰岛素抵抗的相关性分析

目的：探讨男性腹型肥胖患者腹部脂肪面积与糖代谢指标的关系。方法选择21～62岁肥胖男性94例,其中腹围≥90 cm（腹型肥胖组）70例,＜90 cm（均匀肥胖组）24例,登记两组患者的一般资料,测量身高、体质量、腹围、臀围,计算体质量指数（BMI）;受试者空腹行口服葡萄糖耐量试验,检测血糖（0、1、2 h）及胰岛素（0、1、2 h）,计算胰岛素抵抗指数;应用 MRI 测量腹部内脏脂肪面积;比较两组患者血糖、胰岛素及胰岛素抵抗指数的差异,并分析腹型肥胖患者糖代谢相关指标与腹部脂肪面积的相关性。结果腹型肥胖组 BMI、腰围、臀围、胰岛素抵抗指数及腹部脂肪面积均高于均匀肥胖组[（28.67±4.20）、（21.80±1.97）kg/ m2,（99.75±4.07）、（79.50±10.05）cm,（104.42±7.62）、（91.86±4.49）cm,2.60±1.80、1.52±0.73,（153.06±53.23）、（71.78±25.48）cm2],差异均有统计学意义（t值分别为-7.704、-9.583、-7.618、-2.877、-7.184,P 均＜0.05）;腹型肥胖组0、1、2 h 血糖和胰岛素高于均匀肥胖组[（5.89±1.36）、（5.29±0.53）mmol/ L,（10.55±3.07）、（8.76±1.96）mmol/ L,（8.41±3.63）、（6.54±1.50）mmol/ L,（9.71±5.05）、（6.42±2.96）mU/ L,（83.29±64.51）、（33.00±19.82） mU/ L,（27.93±14.98）、（63.56±21.09）mU/ L],差异均有统计学意义（t 值分别为-2.098、-2.671、-2.447,-3.010、-3.784、-3.089,P 均＜0.05）;腹型肥胖患者腹部脂肪面积与年龄、BMI、腹围、臀围、血糖（0、1、2 h）、胰岛素（0、2 h）及胰岛素抵抗指数均呈正相关（ r 值分别为0.254、0.533、0.521、0.615、0.245、0.315、0.294、0.273、0.249、0.225,P 均＜0.05）,校正混杂因素后,年龄（x1）、腹围（x2）及胰岛素抵抗指数（x 3）与腹部内脏脂肪面积成正相关相关（y =1.369x1＋4.472x2＋25.072x3-333.626）。结论与均匀肥胖相比较,腹型肥胖患者的腹部脂肪面积大小与胰岛素抵抗相关。     

血浆C-反应蛋白与肥胖者胰岛素抵抗关系的研究

目的　研究肥胖者中的胰岛素抵抗与C反应蛋白 (CRP)浓度的关系。方法　选择肥胖者及正常对照各10 4例 ,测定血中CRP、胰岛素、血糖、血脂水平 ,肥胖者分为胰岛素抵抗 (IR)组及胰岛素敏感 (IS)组 ,测定两组减轻体重后的上述指标。结果　肥胖组的CRP、胰岛素、甘油三酯、总胆固醇、胰岛素、低密度脂蛋白水平高于对照组 (P <0 .0 1)。肥胖者中 ,IR组CRP、胰岛素水平高于IS组 (P <0 .0 1)。减轻体重后CRP、胰岛素下降 (P <0 .0 1)仅见于IR组。肥胖组 ,仅胰岛素水平与CRP浓度的相关系数有统计学意义 (r =0 .5 6 ,P <0 .0 1)。结论　胰岛素抵抗与CRP浓度有关 ,CRP升高仅见于IR的肥胖者 ,且与随体重下降胰岛素抵抗的改善相平行。     

肥胖者网膜脂肪组织中叉头状转录因子O1、葡萄糖转运体4mRNA的表达及其与胰岛素抵抗相关性的研究

目的观察肥胖者网膜脂肪组织中叉头状转录因子O1（FOXO1）、葡萄糖转运体4（GLUT4）mRNA表达,探讨FOXO1在肥胖和胰岛素抵抗发生中的作用。方法聚集15例肥胖者和17例非肥胖者的网膜脂肪组织应用半定量反转录聚合酶链反应（RT—PCR）测定FOXO1、GLUT4mRNA表达,并测定其他临床指标,分析各指标之间的相关性及与胰岛素敏感性的关系。结果肥胖者FOXO1 mRNA的表达显著高于非肥胖对照组,（0．577±0．038VS0．359±0．023）（P〈0．01）,GLUT4mRNA的表达明显低于非肥胖对照组,（0．386±0．037VS0．646±0．034）（P〈0．01）;网膜脂肪组织FOXO1 mRNA的表达与体质量指数（BMI）、腰臀比（WHR）、空腹胰岛素（FINs）、胰岛素抵抗指数（HOMA—IR）、甘油三酯（TG）的表达呈正相关（r=0．963、0．939、0．974、0．924、0．600,均P〈0．01）,与GLUT4 mRNA的表达呈负相关（r=0．866,P〈0．01）,多元逐步回归分析示BMI、HOMA—IR、GLUT4mRNA为FOXO1mRNA的独立相关因素。结论肥胖者的网膜脂肪组织中的FOXO1表达明显增加,FOXO1可能是肥胖和胰岛素抵抗的联系者,可能是通过减少GLUT4的表达引起肥胖者胰岛素抵抗的。     

Interstitial insulin concentrations determine glucose uptake rates but not insulin resistance in lean and obese men.

Insulin action and obesity are both correlated with the density of muscle capillary supply in humans. Since the altered muscle anatomy in the obese might affect interstitial insulin concentrations and reduce insulin action, we have cannulated peripheral lymphatic vessels in lean and obese males, and compared peripheral lymph insulin concentrations with whole body glucose uptake during a euglycemic, hyperinsulinemic clamp. Lymph insulin concentrations in the lower limb averaged only 34% of arterial insulin concentrations during 150 min of insulin infusion. Obese subjects had the highest arterial (P < or = 0.0001) and lymph insulin (P < 0.005) concentrations, but the lowest glucose uptake rates (P < 0.002). In contrast to the initial steep rise then plateau of arterial insulins, both lymph insulin and whole body glucose uptake rates rose slowly and did not consistently reach a plateau. In each individual, the glucose uptake closely correlated with peripheral lymphatic insulin concentrations (mean r2 = 0.95). The coupling between glucose uptake and lymph insulin (glucose uptake/pmol insulin) was much steeper in lean subjects than in the obese (P < or = 0.0001). These results indicate that even if insulin diffusion into tissues is rate limiting for insulin action, a tissue defect rather than an insulin diffusion defect causes insulin resistance in obese subjects.     

On the paradox insulin resistance/insulin hypersensitivity and obesity: two tales of the same history

Insulin resistance (IR) associated with obesity represents a well-known risk factor for chronic disease. IR development may occur to hinder stressful conditions to provide an appropriate energetic supply to non-insulin-sensitive tissues. However, conditions of stress turn out to be ‘maladaptive’ in the long term, leading to chronic diseases. Paradoxically, insulin hypersensitivity and/or hypersecretion causing post-prandial hypoglycemia resulting in increased food intake and weight gain, can represent an event preceding obesity and IR. By performing an OGTT in obese or obese-prone individuals we observed that tardive post-prandial hypoglycemia (3h from glucose load) is not a rare event (32%); in 12% of cases it paralleled with low insulin levels, resulting in the ‘true insulin hypersensitivity’. By using Matsuda-method, we confirmed the presence of insulin hypersensitivity in this group. Therefore the early recognition of this phenomenon could be useful as a predictive biomarker to identify patients prone to develop obesity and obesity related-disorders.     

Skeletal muscle metabolism and insulin resistance during endotoxin shock in the dog

The effect of locally infused endotoxin on gracilis muscle glucose uptake was determined in anesthetized mongrel dogs. The effects of infusion of small amounts of Escherichia coli endotoxin into the arteries of isolated, innervated, constant flow perfused gracilis muscles on glucose uptake and other metabolic variables were determined. Locally infused endotoxin consistently caused a significant and substantial increase in skeletal muscle glucose uptake with no alterations in muscle arteriovenous difference of insulin, oxygen, carbon dioxode, or pH, or in venous blood hematocrit or temperature. These data demonstrate that endotoxin can act locally to increase glucose uptake by skeletal muscle, independent of the action of insulin or other metabolic factors. During natural (free flow) conditions, glucose uptake by the muscle increased markedly during six hours of shock. Increased glucose uptake occurred concomitantly with muscle ischemia and hypoxia. However, when muscle blood flow was held constant, thereby preventing local muscle ischemia and hypoxia, glucose uptake by the gracilis muscle did not change during shock. These results implicate local muscle ischemia and/or hypoxia as the mediator(s) of the increased muscle glucose uptake during shock. Further studies demonstrated that local muscle hypoxia was the stimulus for increased glucose uptake by skeletal muscle during endotoxin shock, and muscle ischemia per se did not after muscle glucose uptake. Since approximately 50% of body mass is composed of skeletal muscle, the contribution of this organ system to the hypoglycemia of endotoxin shock in the dog may be substantial. The ability of insulin to promote glucose diffusion into skeletal muscle before and during gram-negative endotoxin shock was studied in mongrel dogs anesthetized with sodium pentobarbital. The in vivo, isolated, innervated, constant flow perfused gracilis muscle preparation was used. Prior to shock induction, close intra-arterial insulin infusion resulted in a 320% increase in muscle glucose uptake. However, at one, two, and three hours of endotoxin shock, gracilis muscle glucose uptake was unaltered by insulin infusion. This loss of responsiveness to insulin occurred with no alteration in gracilis muscle oxygen uptake, muscle venous P_O2, or muscle blood flow. During control experiments, however, the muscle response to intra-arterial infusion of insulin (increased glucose uptake) was unaltered during the three-hour control period. These data demonstrate that skeletal muscle insulin resistance develops early and is maintained during three hours of endotoxin shock in the dog.     

Subcutaneous adipose tissue expression of tumour necrosis factor-alpha is not associated with whole body insulin resistance in obese nondiabetic or in type-2 diabetic subjects

BACKGROUND: An association with subcutaneous adipose tissue TNFalpha expression and insulin resistance has been suggested in obesity/type-2 diabetes, but this has not been examined directly. In the first part of the study we investigated whether this association is present in 7 lean, 10 obese nondiabetic and 9 type-2 diabetic men. In the second part of the study we examined the relationship between adipose tissue TNFalpha mRNA levels and BMI in 81 nondiabetic subjects spanning a wide range of BMIs. METHODS: Subcutaneous adipose tissue TNFalpha mRNA levels and insulin sensitivity were determined with quantitative RT-competitive PCR and hyperinsulinaemic clamp, respectively. RESULTS: Subcutaneous adipose tissue TNFalpha mRNA levels were similar in 7 lean and 10 obese nondiabetic and 9 type-2 diabetic men (P = 0.68), and did not change in response to 240-min hyperinsulinaemia. TNFalpha mRNA levels and insulin sensitivity were not correlated. Unexpectedly, no correlation between TNFalpha mRNA and BMI was found. The relationship between adipose tissue TNFalpha mRNA and BMI was examined further in 31 male and 50 female nondiabetic subjects. The subcutaneous adipose tissue TNFalpha mRNA level correlated with BMI in all subjects (rS = 0.32, P < 0.01), and in a subgroup analysis in men (rS = 0.55, P < 0.01) but not in women (rS = - 0.08). The correlation in men was dependent on a fourfold higher TNFalpha mRNA level in 5 morbidly obese men while there was no difference in TNFalpha mRNA levels in lean or obese men. CONCLUSIONS: Subcutaneous adipose tissue TNFalpha expression does not correlate with insulin sensitivity in nondiabetic or type-2 diabetic men; is not regulated by acute hyperinsulinaemia; and is increased only in morbidly obese men.     

Regional fat mass by DXA: high leg fat mass attenuates the relative risk of insulin resistance and dyslipidaemia in obese but not in overweight postmenopausal women

OBJECTIVE: To investigate the influence of regional fat mass (FM) on insulin resistance and dyslipidaemia in obese postmenopausal women (BMI >30 kg/m(2)) compared to overweight women (BMI <30 kg/m(2)). Leg FM may attenuate the increased risk of cardiovascular disease and diabetes imposed by increased trunk FM in normal and overweight postmenopausal women. MATERIAL AND METHODS: Cross-sectional and consecutively referred patients comprising 63 obese and 36 overweight postmenopausal women. Body composition and regional FM by dual X-ray absorptiometry (DXA), fasting glucose, fasting insulin and C-peptide, insulin resistance by homeostasis model assessment (HOMA-IR), insulin sensitivity by quantitative insulin sensitivity check index (QUICKI) and metabolic clearance rate (MCRestOGTT), insulin secretion (HOMAsecr) and serum lipids were assessed. RESULTS: In obese subjects, leg FM was favourably associated with HOMA-IR (p<0.05), QUICKI (p<0.05), fasting glucose (p<0.05), fasting insulin (p<0.05), HOMAsecr (p<0.05) and total cholesterol/HDL ratio (p<0.05). Trunk FM was unfavourably associated with MCRestOGTT (p<0.01), QUICKI (p<0.05) and fasting insulin (p<0.05). Compared to leg FM, leg/trunk FM ratio was more strongly associated with fasting insulin (p<0.001), fasting C-peptide (p<0.001), HOMA-IR (p<0.001), MCRestOGTT (p<0.001), QUICKI (p<0.001), HOMAsecr (p<0.001), fasting glucose (p<0.01) and triglycerides (p<0.01). Stepwise multiple regression demonstrated that leg/trunk FM ratio was the most important variable with partial R (2) = 0.26 (p<0.001) for HOMA and R (2) = 0.37 (p<0.001) when QUICKI was used as the dependent variable. In overweight women, no associations between fat mass and parameters of insulin resistance or dyslipidaemia were found. CONCLUSIONS: A high leg/trunk FM ratio as measured by DXA may give relative protection against diabetes and cardiovascular disease in obese postmenopausal women, but not in overweight women.     

Effects of muscarinic blockade on insulin secretion and on glucose-induced thermogenesis in lean and obese human subjects

To determine whether hyperinsulinaemia of human obesity is dependent on the activity of the parasympathetic nervous system, and whether activation of the parasympathetic nervous system plays a role in glucose-induced thermogenesis, the metabolic effect of a continuous intravenous glucose infusion [44.4 mumol kg-1 body weight (bw) min-1] with or without atropine infusion was assessed in 11 obese patients and 10 lean controls. Compared with lean controls, obese patients had increased basal and glucose-stimulated plasma insulin and C-peptide concentrations and increased plasma glucose concentrations during glucose infusion. Glucose oxidation during i.v. glucose was lower in obese patients than in lean controls. Glucose-induced thermogenesis was similar in obese patients and in lean controls. Atropine infusion did not affect basal plasma glucose, insulin or free fatty acid concentrations nor glucose-stimulated plasma glucose, insulin, C-peptide, glucagon or free fatty acid concentrations in both groups of subjects. Glucose and lipid oxidation rates and glucose-induced thermogenesis were also unaffected by atropine administration. It is concluded that (1) glucose-stimulated hyperinsulinaemia in human obesity is not dependent on a hyperactivity of the parasympathetic nervous system, which indicates that human obesity is different from most animal models of obesity; (2) glucose-induced thermogenesis is similar in obese and lean subjects when a similar load of glucose is administered; (3) inhibition of the parasympathetic nervous system does not affect the thermic effect of i.v. glucose.     

Fat metabolism and its response to infusion of insulin and glucose in patients with advanced chronic obstructive pulmonary disease

Summary. In order to investigate fat metabolism and the regulation of lipolysis and blood fuel metabolites by insulin, nine patients with chronic obstructive pulmonary disease (COPD) with chronic hypoxaemia and seven healthy control subjects of similar age were investigated by determination of the turnover rate of free fatty acids (TOR), using 1-¹⁴C-oleic acid as a tracer, and arterial concentrations of FFA, glycerol and 3-hydroxybutyrate. The measurements were performed in the basal state and during insulin and glucose infusion, aiming at euglycaemia at insulin levels of 50 and 100 mU l^-1. The subjects' ages were 64±2.7 and 66±1.1 (mean±SEM) years in the COPD and control groups, respectively. TOR was 0.73±0.06 and 0.52±0.02 mmol min^-1 (P<0.05) in the basal state, 0.33±0.04 and 0.30±0.02 at an insulin level of 50 mU I^-1 and 0.32±0.08 and 0.24±0.02 at an insulin level of 100 mU I^-1, in the COPD and control groups, respectively. Arterial FFA concentration was 0.98±0.08 and 0.75±0.06 mmol 1^-1 (P<0.05) in the basal state in the COPD and control groups, respectively. During the clamp, the decrease in FFA mirrored that in TOR. The results show that the state of lipolysis is increased in severe COPD patients with chronic hypoxaemia. Furthermore, the results suggest a reduced effect of insulin in lipolysis.