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 insulin-like growth factor-I on glucose tolerance, insulin levels, and insulin secretion.

Insulin-like growth factor-I (IGF-I) and insulin interact with related receptors to lower plasma glucose and to exert mitogenic effects. Recombinant human IGF-I (rhIGF-I) was recently shown to decrease serum levels of insulin and C-peptide in fasted normal subjects without affecting plasma glucose levels. In this study we have investigated in six healthy volunteers the responses of glucose, insulin, and C-peptide levels to intravenous rhIGF-I infusions (7 and 14 micrograms/kg.h) during standard oral glucose tolerance tests (oGTT) and meal tolerance tests (MTT), respectively. Glucose tolerance remained unchanged during the rhIGF-I infusions in the face of lowered insulin and C-peptide levels. The decreased insulin/glucose-ratio presumably is caused by an enhanced tissue sensitivity to insulin. The lowered area under the insulin curve during oGTT and MTT as a result of the administration of rhIGF-I were related to the fasting insulin levels during saline infusion (oGTT: r = 0.825, P less than 0.05; MTT: r = 0.895, P less than 0.02). RhIGF-I, however, did not alter the ratio between C-peptide and insulin, suggesting that the metabolic clearance of endogenous insulin remained unchanged. In conclusion, rhIGF-I increased glucose disposal and directly suppressed insulin secretion. RhIGF-I probably increased insulin sensitivity as a result of decreased insulin levels and suppressed growth hormone secretion. RhIGF-I, therefore, may be therapeutically useful in insulin resistance of type 2 diabetes, obesity, and hyperlipidemia.     

诺和锐30强化治疗对初诊2型糖尿病患者血糖及胰岛功能的影响

目的探讨诺和锐30强化治疗对初诊2型糖尿病患者血糖及胰岛功能的影响。方法对40例初诊2型糖尿病患者进行2周的诺和锐30治疗,分析治疗前后空腹血糖（FPG）及餐后2h血糖（2hPG）、糖化血红蛋白（HbAlc）、静脉葡萄糖耐量试验第一时项胰岛素及C肽分泌和胰岛素及C肽曲线下面积、胰岛素抵抗指数、胰岛素分泌指数、胰岛素敏感指数、空腹胰岛素（FINS）与FPG比值。结果诺和锐30治疗后,FPG、2hPG、HbAlc、胰岛素抵抗指数均较治疗前明显下降（P〈0．01）;窄腹及第一时项胰岛素和C肽的分泌、胰岛素及C肽曲线下面积、FINS与FPG比值、胰岛素分泌指数、胰岛素敏感指数均较治疗前明显升高（P〈0．01）。结论诺和锐30强化治疗能显著改善初诊2型糖尿病患者的血糖及胰岛功能。     

Insulin and C-peptide secretion in non-insulin-dependent diabetes mellitus and its response to dietary therapy

We studied insulin and C-peptide levels in patients with non-insulin-dependentdiabetes mellitus (NIDDM) during standard oral or intravenousglucose tolerance tests (GTT) at the time of diagnosis and after3 months dietary therapy. On the second occasion they also hadan ‘augmented’ GTT, in which slow intravenous infusionof glucose raised basal plasma glucose to a level similar tothat at the time of diagnosis. Eight patients had oral tests,and seven patients intravenous tests. In both groups, dietarytherapy significantly reduced fasting and peak plasma glucose(p<0.05 for oral; p<0.01 for intravenous GTT). Serum insulinlevels during conventional oral GTT were not significantly differentafter dietary therapy compared to diagnosis, but were significantlyhigher during the ‘augmented’ oral GTT (p<0.05).In those patients who underwent intravenous GTT, there was asignificant increase in both the total amount of insulin secreted(0–60 min) and in first-phase insulin secretion (0–10min) during the ‘augmented’ test compared to diagnosis(p<0.01), but first-phase insulin secretion during the conventionalintravenous GTT was unchanged. Serum C-peptide responses werealso greater during ‘augmented’ tests (p<0.05),similar in pattern to serum insulin. There is a relative deficiencyin insulin secretion in untreated NIDDM, which can be reversedby dietary therapy. It is essential to study insulin and C-peptidesecretion in controlled ‘fasting’ glucose conditions.     

Polymorphism at the 5'' end flanking region of the insulin gene is associated with reduced insulin secretion in healthy individuals

Sixty-four unrelated healthy subjects were studied for the detection of a DNA polymorphism at the 5' end of the insulin gene. No significant difference between the groups was found in blood glucose values at fasting and after an oral glucose load. A significant association was found between fasting (P less than 0.05) and after load plasma C-peptide levels (P less than 0.01) and the presence of a 1.6 Kb insertion at the 5' end of the insulin gene. A gene dose-dependent effect was noted, class 3/3 individuals having the lowest after-load C-peptide concentration and class 1/3 an intermediate level (F for the linear trend: P = 0.007). This might suggest that insulin gene polymorphism affects insulin secretion in healthy individuals. In order to confirm this, a subgroup of six class 3/3 and eight class 1/1 individuals subsequently underwent a hyperglycaemic clamp. The tissue sensitivity to insulin was similar in the two groups but glucose-stimulated insulin secretion was markedly impaired in homozygotes for the class 3 allele. In this group, insulin secretion was, on average, only one-third of that in class 1/1 individuals (P less than 0.02). Similarly impaired in class 3/3 persons was the glucose + arginine-stimulated insulin secretion (P less than 0.05). We conclude that the polymorphism at the 5' end of the insulin gene is associated with variations in insulin secretion in healthy humans.     

Prolonged fasting hypoglycemia due to insulin antibodies in patient with non-insulin-dependent diabetes mellitus: effect of insulin withdrawal on insulin-antibody-binding kinetics

Fasting hypoglycemia, which persisted for 3 days after insulin treatment was stopped, occurred in a patient with non-insulin-dependent diabetes mellitus who had inappropriate plasma free-insulin levels (18-25 microU/ml) and extremely high antibody-bound insulin (greater than 20,000 microU/ml) but normal counter-regulatory hormone secretion and plasma C-peptide levels. The amount of antibody-bound insulin decreased in a biphasic pattern over 13 mo of observation with an initial half-life of 35 days and a more gradual decrease with a half-life of 160 days. The number of high-affinity antibody binding sites was virtually identical to the amount of antibody-bound insulin in the patient's plasma. We conclude that the patient's fasting hyperinsulinemia and hypoglycemia were due to release of antibody-bound insulin.     

Response of glucose disposal to hyperinsulinaemia in human hypothyroidism and hyperthyroidism

We have examined insulin action on glucose metabolism in six hypothyroid patients before and after regular thyroid hormone treatment, and in six healthy volunteers before and after transient induction of moderate hyperthyroidism. Insulin was infused under euglycaemic and eukalaemic clamps. An appropriate amino acid infusion was used to blunt insulin-induced decreases in amino acid levels. Glucose kinetics were assessed using a primed continuous infusion of [6,6-(2)H(2)]glucose. The results showed that basal plasma insulin and glucose levels (i.e. before infusion) were similar in each case. Despite similar insulin infusion rates, the plateau value of insulin was lower after thyroid treatment in both hypothyroid patients and healthy volunteers. The rate of exogenous glucose needed to maintain plasma glucose at a steady-state level was increased by thyroid hormone in hypothyroid patients (P <0.05), but not in healthy volunteers. Thyroid treatment resulted in a significant increase in basal glucose disposal in both groups (P <0.05). Insulin, in conjunction with glucose and amino acids, significantly stimulated glucose disposal (P <0.05) under all conditions. The incremental increase in glucose disposal after infusion tended to be higher following thyroid hormone treatment, but this was not statistically significant. However, the ratio of the incremental increase in glucose disposal to the increase in plasma insulin was significantly improved after thyroid hormone treatment in hypothyroid patients (P <0.05). It was also increased in healthy volunteers, but not significantly. We conclude that thyroid hormones improve the ability of insulin to stimulate glucose disposal related to insulinaemia. This phenomenon may be highly sensitive, because it was only apparent at low thyroid hormone levels.     

The effects of the menopause on insulin sensitivity, secretion and elimination in non-obese, healthy women

Abstract. We have carried out intravenous glucose tolerance tests with measurement of plasma glucose, insulin and C-peptide concentrations on 66 premeno-pausal and 92 postmenopausal non-obese Caucasian women. After adjustment for the effects of a number of possible confounding variables, including age and body mass index, there was little difference between pre and postmenopausal women in glucose and insulin concentrations either fasting or in response to intravenous glucose. Mathematical modelling analysis of the resultant plasma concentration profiles was used to obtain measures of insulin sensitivity, secretion and elimination, and non-insulin dependent glucose disposal. We found reciprocal differences in mean insulin sensitivity (increased by 50%) and non-insulin dependent glucose disposal (decreased by 30%). Plasma C-peptide response and pancreatic insulin secretion were markedly lower in the postmenopausal group (- 35% and -50% respectively). However, the rate constant for insulin elimination was also lower in these women. As a result, intravenous glucose tolerance test plasma insulin concentrations were not significantly different between the two groups. We conclude that, despite the occurrence of little or no variation in plasma glucose and insulin concentrations, the menopause is associated with significant changes in insulin metabolism.     

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.     

几种化学发光检测系统测定血清胰岛素和C-肽临床效果的评估

目的探讨不同化学发光检测系统测定血清胰岛素、C-肽临床结果间的可比性和符合程度,并试图找到不受方法学影响,能够反映两者动态变化规律的通用参数。方法选择40名做胰岛素和C-肽释放试验的患者（均未使用外源性胰岛素治疗）,同时应用三种化学发光免疫分析系统,检测同一个体在OGTT中各时间点血清胰岛素和C-肽的浓度,并分别计算两者在服糖后各时间点浓度与其空腹浓度的比值（简称比值）。结果①血清胰岛素或C-肽测定结果在任意两系统间的差异均非常显著（均为P〈0.001）,且高度相关（胰岛素：r=0.946-0.977;C-肽：r=0.959-0.996）。②服糖后同一时间点胰岛素的上述比值在任意两系统间均显著相关（均为P〈0.05）,且均无统计学差异（均为P〉0.05）,C-肽也可得到相似结果。③对于相同检测系统,同一时间点两者的上述比值间差异显著（P〈0.05）且C-肽的比值显著低于胰岛素。结论血清胰岛素或C-肽的测定结果在不同检测系统间差异很大,虽均具有很好的相关性,但不能互相通用。而在OGTT中,服糖后同一时间点两者浓度与各自空腹浓度的比值在不同检测系统间的差异似乎并不显著,有望成为不同检测系统间互认的指标。至于C-肽在反映胰腺β细胞功能的敏感度上显著低于胰岛素的问题,其临床应用尚有待进一步研究。     

Nocturnal insulin and C-peptide rhythms in normal subjects

Immunoreactive insulin and C-peptide reactive plasma levels in venous blood were studied between 0100 and 0820 h in 10 healthy volunteers to assess nocturnal endogenous insulin secretion and its peripheral extraction. Insulin secretion appeared significantly reduced after 0600 h. No correlations were observed between counterregulatory hormones and insulin secretion during this period. Plasma glucose remained stable throughout the study. An increased peripheral sensitivity to insulin after 0600 h is suggested to explain reduced secretion of insulin.     

Decreased serum C-peptide/insulin molar ratios after oral glucose ingestion in hyperthyroid patients

Since C-peptide/immunoreactive insulin (IRI) molar ratios may reflect hepatic extraction of insulin, we measured simultaneous serum glucose, IRI, and C-peptide levels during fasting and 30, 60, 90, 120, and 180 min after 75 g of oral glucose in 10 hyperthyroid patients and 10 age- and weight-matched controls. Mean fasting serum glucose and IRI levels were significantly higher in the hyperthyroid versus control subjects (glucose: 4.9 +/- 0.3 mmol/L versus 4.36 +/- 0.11 mmol/L, P less than 0.01; IRI: 0.10 +/- 0.02 pmol/ml versus 0.05 +/- 0.01 pmol/ml; P less than 0.025). After glucose, mean serum glucose levels were significantly higher in the hyperthyroid versus control subjects at all times studied except for 180 min (P less than 0.01). Mean IRI levels were significantly higher at all times studied including 180 min (P less than 0.01). Mean fasting C-peptide levels were significantly greater in the hyperthyroid patients compared with the controls (1.2 +/- 0.25 pmol/ml versus 0.62 +/- 0.09 pmol/ml; P less than 0.025). After oral glucose, mean C-peptide levels were significantly higher (P less than 0.025) in the hyperthyroid compared with control subjects at 30-60 min but not at 90-180 min. Molar ratios of C-peptide/IRI were significantly lower (P less than 0.05) in the hyperthyroid versus control subjects at all times studied except fasting. In summary, glucose intolerance and hyperinsulinism occur in hyperthyroidism. In addition, C-peptide/IRI molar ratios are reduced after oral glucose ingestion.     

Improved glycemic control and enhanced insulin sensitivity in type 2 diabetic subjects treated with pioglitazone

OBJECTIVE: To elucidate the effects of pioglitazone treatment on glucose and lipid metabolism in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: A total of 23 diabetic patients (age 30-70 years BMI < 36 kg/m2) who being treated with a stable dose of sulfonylurea were randomly assigned to receive either placebo (n = 11) or pioglitazone (45 mg/day) (n = 12) for 16 weeks. Before and after 16 weeks of treatment, all subjects received a 75-g oral glucose tolerance test (OGTT) and hepatic peripheral insulin sensitivity was measured with a two-step euglycemic insulin (40 and 160 mU x min(-1) x m(-2) clamp performed with 3-[3H]glucose and indirect calorimetry HbA1c measured monthly throughout the study period. RESULTS: After 16 weeks of pioglitazone treatment, the fasting plasma glucose (FPG; 184 +/- 15 to 135 +/- 11 mg/dl, P < 0.01), mean plasma glucose during OGTT(293 +/- 12 to 225 +/- 14 mg/dl, P < 0.01), and HbA1c (8.9 +/- 0.3 to 7.2 +/- 0.5%, P < 0.01 ) decreased significantly without change in fasting or glucose-stimulated insulin/C-peptide concentrations. Fasting plasma free fatty acid (FFA; 647 +/- 39 to 478 +/- 49) microEq/l, P < 0.01) and mean plasma FFA during OGTT (485 +/- 30 to 347 +/- 33 microEq/l, P < 0.01) decreased significantly after pioglitazone treatment. Before and after pioglitazone treatment, basal endogenous glucose prodution (EGP) and FPG were strongly correlated (r = 0.67, P < 0.01). EGP during the first insulin clamp step was significantly decreased after pioglitazone treatment (P < 0.05) whereas insulin-stimulated total and nonoxidative glucose disposal during the second insulin clamp was increased (P < 0.01). The change in FPG was related to the change in basal EGP, EGP during the first insulin clamp step, and total glucose disposal during the second insulin clamp step. The change in mean plasma glucose concentration during the OGGTT was strongly related to the change in total body glucose disposl during the second insulin clamp step. CONCLUSIONS: These results suggest that pioglitazone therapy in type 2 diabetic patients decreases lasting and postprandial plasma glucose levels by improving hepatic and peripheral (muscle) tissue sensitivity to insulin.     

Serum leptin levels in type 1 diabetic and obese children: relation to insulin levels

OBJECTIVES: To compare serum leptin levels in type 1 diabetic and obese children. DESIGN AND METHODS: We studied serum leptin levels in 35 type 1 diabetic, 32 obese, and 35 healthy children. Seven of 35 were new-onset diabetics with ketoacidosis. C-peptide (CPE) levels were used for estimating insulin secretion. RESULTS: Serum leptin levels were lower in diabetics than in controls (p<0.001). Obese children had higher leptin and CPE levels than diabetics and controls. In new-onset diabetics, 1 month insulin treatment did not cause any change in leptin levels (p>0.05). Leptin was correlated positively with body mass index and CPE (p<0.001) and inversely with glucose (p = 0.001) and HbA1c (p<0.05) in the combined group. HbA1c and gender were the independent predictors of leptin in diabetic children (p<0.01). CONCLUSIONS: Low serum leptin levels in type 1 diabetic children may be due to chronic insulin deficiency related with their metabolic control. Leptin and insulin may have complementary roles in maintaining a stable body weight.     

Relationship between habitual physical activity and insulin levels among nondiabetic men and women. San Luis Valley Diabetes Study.

OBJECTIVE: To determine whether higher levels of physical activity would be associated with lower fasting insulin and C-peptide levels in a free-living nondiabetic population. RESEARCH DESIGN AND METHODS: A cross-sectional study was conducted with a Hispanic and non-Hispanic white population of 442 men and 489 women with normal glucose tolerance (by World Health Organization criteria) in two rural Colorado counties. Total physical activity was assessed by a 7-day physical activity recall from which metabolic equivalents were estimated. Relationships between metabolic equivalents and fasting insulin and C-peptide were assessed while considering obesity, age, and other risk factors known to influence fasting insulin levels. RESULTS: Among all subjects, univariate analyses showed that higher activity levels were associated with lower mean fasting insulin and C-peptide levels (P less than or equal to 0.05). Multiple linear regression showed that higher activity was significantly associated with lower values of log fasting insulin and C-peptide levels in men only (P less than 0.001) independent of obesity, fat distribution, and age. Men in the highest tertile of activity had an adjusted mean fasting insulin level of 59.2 pM and fasting C-peptide level of 0.5 nM compared with a fasting insulin level of 72.7 pM and fasting C-peptide level of 0.6 mM for men in the lowest tertile of activity. The magnitude of the inverse association between activity and insulin was greatest in older rather than younger men. Physical activity was not associated with fasting insulin or C-peptide levels in women in the multivariate analyses. CONCLUSIONS: Based on cross-sectional data, we conclude that higher levels of habitual physical activity are associated with lower fasting insulin and C-peptide levels in Hispanic and non-Hispanic white men.     

Defects in insulin secretion and insulin action in non-insulin-dependent diabetes mellitus are inherited. Metabolic studies on offspring of diabetic probands.

No studies are available that have compared early defects in glucose metabolism in the offspring of insulin-deficient and insulin-resistant probands with non-insulin-dependent diabetes mellitus (NIDDM). To investigate this issue, we evaluated insulin secretion capacity with oral and intravenous glucose tolerance tests and with the hyperglycemic clamp, and insulin action with the euglycemic insulin clamp in 20 offspring of NIDDM patients with low fasting C-peptide (+/-450 pmol/liter), reflecting deficient insulin secretion (IS-group), 18 offspring of NIDDM patients with high fasting C-peptide (>/= 880 pmol/liter), reflecting insulin resistance (IR-group), and 14 healthy control subjects without a family history of NIDDM. The frequency of impaired glucose tolerance was 45.0% in the IS-group and 50% in the IR-group. The IS-group had lower insulin-glucose response at 30 min in the oral glucose tolerance test (85.2+/-10.0 pmol insulin per mmol glucose) than the control group (136.4+/-23.1 pmol insulin per mmol glucose; P < 0.05) and the IR-group (115.6+/-11.8 pmol insulin per mmol glucose; P = 0.05). Furthermore, the acute insulin response during the first 10 min of an intravenous glucose tolerance test was lower in the IS-group than in the IR-group. Maximal insulin secretion capacity evaluated by C-peptide levels during the hyperglycemic clamp did not differ between the groups. The IR-group had lower rates of whole body glucose uptake (60.1+/-4.6 micromol per lean body mass per minute) than did the control group (84.2+/-5.0 micromol per lean body mass per minute; P < 0.001) or the IS-group (82.6+/-5.9 micromol per lean body mass per minute; P < 0.01) and this was due to reduced glucose nonoxidation. To conclude, both impaired insulin secretion and insulin action seem to be inherited and could represent the primary defects in glucose metabolism in the offspring of NIDDM probands.     

What is a normal glucose value? Differences in indexes of plasma glucose homeostasis in subjects with normal fasting glucose

OBJECTIVE: To evaluate differences in indexes of plasma glucose/insulin homeostasis and cardiovascular disease risk factors among subjects with normal fasting glucose (NFG), impaired fasting glucose, or glucose intolerance. Although individuals with fasting plasma glucose (FPG) concentrations > 5.4 mmol/l but < 6.1 mmol/l have been shown to have an increased risk of developing type 2 diabetes over 5 years, little is known about glucose metabolism abnormalities in this population. RESEARCH DESIGN AND METHODS: We compared insulin secretion and insulin sensitivity using several indexes derived from an oral glucose tolerance test (OGTT) in 668 subjects from the Quebec Family Study who had varying degrees of FPG. RESULTS: There was a progressive decline in indexes of beta-cell function and insulin sensitivity when moving from NFG to type 2 diabetes. Compared with subjects with low NFG (FPG < 4.9 mmol/l), subjects with high NFG (FPG 5.3-6.1 mmol/l) were more insulin resistant (P < 0.01), had higher insulin and C-peptide responses during an OGTT (P < 0.05), and had reduced insulin secretion (corrected for insulin resistance). Subjects with high NFG were also characterized by higher plasma triglyceride levels and reduced HDL cholesterol concentrations and by a smaller LDL particle size. All these differences remained significant, even after adjustment for age, sex, BMI, and waist circumference. In addition, subjects with mid NFG (FPG 4.9-5.3 mmol/l) were characterized by impaired insulin secretion, decreased insulin sensitivity, higher triglyceride concentrations, and lower HDL cholesterol concentrations compared with subjects with low NFG. CONCLUSIONS: Independent of age, sex, and adiposity, there are differences in indexes of plasma glucose/insulin homeostasis and in cardiovascular risk factors among subjects with low, mid, and high NFG, suggesting the presence, in the upper normal glucose range, of abnormalities in glucose homeostasis, which may predispose to type 2 diabetes.     

The effect of a very low calorie diet on insulin sensitivity, beta cell function, insulin clearance, incretin hormone secretion, androgen levels and body composition in obese young women

Abstract Objective. Evaluation of the effect of an 8-week very low calorie diet (VLCD, 500-600 kcal daily) on weight, body fat distribution, glucose, insulin and lipid metabolism, androgen levels and incretin secretion in obese women. Methods. Seventeen overweight women (BMI >28) were recruited to the study. Glucose, insulin and lipid metabolism were evaluated by euglycemic clamp technique, indirect calorimetry and an oral glucose tolerance test (OGTT). Insulin sensitivity was calculated as glucose disposal rate (GDR) and insulin sensitivity index (ISI), and also by HOMA-IR. Insulin secretion rate (ISR) was calculated from plasma C-peptide measurements. Secretion of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) was measured during an oral glucose tolerance test. Abdominal fat distribution was assessed by dual x-ray absorptiometry scan and computed tomography. Results. Ten women completed the intervention. The subjects lost an average 11% of their baseline weight. There was a significant loss of subcutaneous abdominal fatty tissue (p <0.01) and intra-abdominal fatty tissue (p =0.05). Whole body (HOMA-IR) (p <0.05) insulin sensitivity increased significantly, but peripheral (ISI) insulin sensitivity was unaltered after weight loss. GIP increased (p <0.05) and GLP-1 was unaltered after the dietary intervention. Insulin responses did not differ before and after dietary intervention, however, a significant increase in insulin clearance (p <0.05) was observed. The weight loss resulted in a significant decrease in free testosterone. Conclusion. A VLCD is an effective weight loss treatment, which results in an immediate improvement in several metabolic parameters.     

Insulin resistance--a risk factor for coronary heart disease?

Fasting insulin secretion was assessed by measuring fasting serum C-peptide levels in 529 women and 399 men aged 18-90 years, to study the relationship between insulin secretion, insulin resistance and risk factors for coronary heart disease. Subjects with low serum high density lipoprotein (HDL) cholesterol levels showed higher mean serum insulin and C-peptide levels than subjects with normal HDL cholesterol levels. In male subjects these differences were significant for both serum insulin and serum C-peptide results (P less than 0.005). In female subjects serum insulin results differed significantly (P less than 0.0005) but for the difference in mean serum C-peptide levels P was equal to 0.012. Fasting serum C-peptide correlated negatively with serum HDL cholesterol. However, serum C-peptide also correlated with serum triglyceride and serum triglyceride correlated negatively with serum HDL cholesterol. Each correlation was statistically significant (P less than 0.001). Multiple regression analysis suggested that the apparent association of C-peptide with HDL cholesterol was a consequence of the interrelated association between C-peptide, triglyceride and HDL cholesterol. The analysis was consistent with the hypothesis that obesity and increased insulin resistance were associated with increased insulin secretion and in turn with high serum triglyceride levels and consequentially low levels of serum HDL cholesterol. The data were compatible with the suggestion that insulin resistance rather than fasting insulin concentration per se could be a risk factor for coronary heart disease.     

Fasting plasma C-peptide levels in health and impaired glucose tolerance: relations to blood glucose and relative body weight

Pancreatic B-cell function was studied as part of a health control examination by measuring fasting plasma C-peptide concentration in 433 44-55 year-old males with normal glucose tolerance. Fasting C-peptide levels were correlated with relative body weight (r = 0.48) and fasting blood glucose concentrations (r = 0.43), yielding a multiple correlation coefficient of 0.56, and the multiple regression equation: FCP (nmol/l) = -0.89 + 0.61 X RBW + 0.16 X FBG (mmol/l). (FCP = fasting plasma C-peptide, RBW = relative body weight, FBG = fasting blood glucose). In 26 subjects with impaired glucose tolerance, fasting plasma C-peptide levels were even more strongly correlated with relative body weight (r = 0.63) and fasting blood glucose concentrations (r = 0.47). Subjects older than 52 years had a significantly higher fasting C-peptide level than younger subjects (p less than 0.01). In the 26 subjects with impaired glucose tolerance, fasting plasma C-peptide levels were not significantly different from those in the 433 men with normal glucose tolerance. However, when compared to a group with normal glucose tolerance matched for relative body weight, the subjects with impaired glucose tolerance had an elevated fasting blood glucose level (p less than 0.01) without difference in C-peptide level, suggesting a reduced insulin sensitivity. It is concluded that, in order to evaluate B-cell secretory function by determining fasting plasma C-peptide concentration, the relative body weight and simultaneous blood glucose concentration should be taken into consideration.