Nocturnal elevation of glucose levels during fasting in noninsulin-dependent diabetes

To define the spontaneous diurnal variations in glucose regulation during fasting in noninsulin-dependent diabetes (NIDDM), we measured circulating levels of glucose, insulin, C-peptide, GH, cortisol, and glucagon at 15-min intervals in 11 patients with untreated diabetes and 7 matched control subjects studied during a 24-h period. The rates of insulin secretion were derived from the concentrations of C-peptide by deconvolution using a two-compartment mathematical model for C-peptide distribution and metabolism. In both groups of subjects, despite continued fasting, glucose levels stopped declining in the evening and subsequently rose throughout the night to reach a morning maximum. Elevated levels persisted until noon. The morning glucose maximum corresponded to a relative increase of 23.8 +/- 5.5% above the evening nadir in NIDDM patients and 13.2 +/- 4.6% in nondiabetic subjects (P less than 0.05). In NIDDM patients, insulin levels and insulin secretion rates did not parallel the nocturnal glucose changes. In contrast, in control subjects, this nocturnal glucose rise coincided with a similar increase in insulin secretion rates. Cortisol concentrations in patients with NIDDM were higher than those in control subjects throughout the study period (P less than 0.001) and rose earlier in the evening than in control subjects, thus failing to demonstrate the normal nocturnal suppression. In both groups of subjects, the nighttime glucose elevation was temporally and quantitatively correlated with the circadian cortisol rise. GH secretion was increased in the evening and nighttime periods compared to the daytime values, and in NIDDM patients, but not in control subjects, the size of the morning glucose elevation was directly related to the magnitude of this increase in GH secretion (r = 0.88; P less than 0.01). Glucagon concentrations were similar in both groups of subjects and remained essentially constant throughout the study period. We hypothesize that the nocturnal glucose rise that occurs during fasting represents a normal diurnal variation in the set-point of glucose regulation amplified by counterregulatory mechanisms activated by the fasting condition.     

超重及肥胖人群血清网膜素-1水平的变化

目的 探讨在南京地区人群中超重及肥胖者血清网膜素-1水平的变化及其与体重指数、腰围、脂联素之间的相关性.方法 从2008年3月至7月全国糖尿病和代谢综合征患病率及变迁调查江苏分中心的南京地区调查人群中,选取42例超重及肥胖者和55名健康对照者,分别测定体重指数、腰围、空腹胰岛素、窄腹血糖、血脂、血清网膜素-1及脂联素的水平,计算腰臀比及胰岛素抵抗指数.采用SPSS 15.0软件进行统计学分析,血清网膜素-1和各指标问的相关性分析采用Pearson相关分析法.结果 健康对照者的血清网膜素-1浓度为(0.024±0.012)μg/L,脂联素浓度为(7.7±2.4)mg/L,超重及肥胖者的血清网膜素-1浓度为(0.016±0.007)μg/L,脂联素浓度为(6.4±3.1)mg/L.结果 显示超重及肥胖者的血清网膜素-1及脂联素水平明显低于健康对照者(P<0.05),且相关分析表明血清网膜素-1与体重指数(r=-0.321,P<0.05)、腰围(r=-0.312,P<0.05)、腰臀比(r=0.243,P<0.05)及甘油三脂(r=-0.220,P<0.05)之间旱显著负相关,与脂联索(r=0.232,P<0.05)呈明显正相关.结论 超莆及肥胖者的血清网膜素-1水平较健康对照者显著下降,且血清网膜素-1浓度变化与脂联素之间呈正相关,提示网膜素水平变化可能与肥胖、胰岛素抵抗和2型糖尿病密切相关.     

Insulin hypersecretion: a distinctive feature between essential and secondary hypertension.

Several studies have demonstrated that patients with hypertension have greater plasma insulin levels than normotensive subjects. The aim of the present study was to clarify if hyperinsulinemia in hypertension is a consequence of either increased pancreatic secretion or decreased hepatic clearance, and to determine whether abnormalities of glucose metabolism are equally present in essential and secondary hypertension. In an observational cross-sectional study, fasting blood glucose, plasma insulin, and plasma C-peptide levels were measured in five patient groups: 34 lean normotensive, 19 overweight normotensive, 25 lean essential hypertensive, 27 overweight essential hypertensive, and 20 secondary hypertensive subjects. The blood glucose/plasma insulin and plasma insulin/plasma C-peptide ratios were calculated as indexes of insulin sensitivity and hepatic insulin clearance, respectively. Subjects with essential hypertension and, to a greater extent, those who were overweight, exhibited significantly higher fasting insulin and C-peptide levels and significantly lower glucose/insulin ratios as compared with lean normotensive subjects. In contrast, no differences were observed between secondary hypertensive and control subjects. Mean blood pressure was significantly and independently correlated to body mass index, plasma insulin and plasma C-peptide levels, and the glucose/insulin ratio. In lean essential hypertensive and secondary hypertensive subjects, the insulin/C-peptide ratios were comparable to controls, indicating normal hepatic insulin clearance. In both overweight groups, a trend to increased insulin/C-peptide ratios was observed. This study shows that in essential hypertensive subjects, hyperinsulinemia is caused by insulin hypersecretion, whereas in overweight subjects, both increased insulin secretion and decreased hepatic insulin clearance might be involved.(ABSTRACT TRUNCATED AT 250 WORDS)     

Serum adiponectin concentrations during a 72-hour fast in over- and normal-weight humans

OBJECTIVE: Adiponectin is currently considered an important link between obesity and insulin resistance, since circulating levels of this insulin sensitizing hormone have consistently been found to be reduced in obese subjects. However, until now it is not known how the secretion of adiponectin is regulated in response to acute metabolic changes. Here, we assessed the influence of complete fasting for 72 h on serum adiponectin levels. DESIGN: Between group comparison of repeated measurements. SUBJECTS: In total, 18 normal-weight (mean+/-s.e.m. BMI: 22.2+/-0.4 kg/m(2); age: 39.2+/-4.4 y) and nine over-weight (BMI: 33.2+/-1.8 kg/m(2); age: 36.9+/-4.5 y) subjects. MEASUREMENTS: Serum adiponectin levels were measured every 4 h during a 72-h fasting period. Additionally, concentrations of plasma glucose and serum insulin and leptin were assessed at the beginning and in the end of the fasting experiment. Insulin resistance was estimated using the homeostasis model assessment (HOMA). RESULTS: While concentrations of glucose, insulin, and leptin decreased across the fasting period by 31.0, 33.1 and 60.0%, respectively (all P<0.005), adiponectin levels remained unchanged (P=0.817). Overall, over-weight subjects exhibited slightly lower adiponectin levels than normal-weight subjects (P=0.092), but there was no difference in the time course of adiponectin levels during fasting between these two groups (P=0.970). Although, averaged adiponectin levels before and after fasting did not systematically differ, individual changes in adiponectin levels across fasting displayed a slight but significant inverse correlation with changes in plasma glucose concentration (r=-0.42, P=0.03). DISCUSSION: The data show that serum adiponectin concentrations remain remarkably stable during 72 h of fasting in normal- and over-weight subjects. Thus, adiponectin appears to reflect primarily long-term changes in body weight with little evidence for a dependence on short-term regulatory influences.     

Altered circadian blood pressure profile in patients with active acromegaly. Relationship with left ventricular mass and hormonal values

To determine the relationships between the circadian blood pressure profile and left ventricular mass, hormonal pattern and insulin sensitivity indices in patients with active acromegaly, ambulatory 24-h blood pressure monitoring (ABPM) was recorded in 25 subjects (47.0 +/- 15.1 years, range 23-72). Serum growth hormone (GH) and insulin-like growth factor-1, fasting and mean plasma glucose and insulin during oral glucose tolerance test (OGTT), insulinogenic index, the sum of the plasma insulin levels and the homeostasis model insulin resistance index (Homa's index) were determined. Left ventricular mass index (LVMI) was calculated from two-dimensional guided M-mode echocardiogram. The prevalence of hypertension was 56% (n = 14) and 40% (n = 10) according to sphygmomanometric measurements and ABPM, respectively. Non-dipping profile was observed in six of 10 hypertensives and in six of 15 normotensives. Serum growth hormone, fasting glucose, the area under the serum insulin curve and LVMI were higher for acromegalics with non-dipping profile than for dippers (all of them, P < 0.05). In non-dippers daytime heart rate was higher than night time (P < 0.001). In conclusion, the main observations in the present study suggested that both normotensive and hypertensive acromegalics had a highly prevalent non-dipping profile with a preserved circadian pattern of heart rate, that was associated with higher levels of serum GH. The disturbance in nocturnal blood fall in normotensives was associated with a decreased insulin sensitivity. The role of GH in blood pressure circadian rhythm regulation in essential hypertension deserves further studies.     

Factors affecting fasting serum C-peptide levels in Micronesians: comparison with a Caucasoid population

Summary Fasting serum C-peptide immunoreactivity was determined on Nauruans, a Micronesian population with a high prevalence of diabetes. In Micronesian subjects neither age nor gender had a significant effect on fasting serum C-peptide. In non-diabetic subjects, as has been shown previously for Caucasiod subjects, both obesity and fasting plasma glucose levels were determinants of fasting serum C-peptide. Obesity was the major determinant. Taken overall, mean fasting serum C-peptide increased then possibly fell in subjects grouped by increasing 2-h post-glucose plasma glucose levels. Mean fasting serum C-peptide in newly-diagnosed diabetic subjects was greater than that in non-diabetic subjects with a similar degree of obesity, supporting the concept that the transition to diabetes may be associated with an increase in insulin resistance. The data for non-diabetic subjects were compared with serum C-peptide measured in the same laboratory on samples from a Caucasoid population in Busselton, Western Australia. There was no difference in fasting serum C-peptide level between Micronesian and Caucasoid subjects approximately matched for obesity and fasting plasma glucose levels.     

The insulin-like growth factor binding protein-1 in low and high insulin responders before and during dexamethasone treatment.

To investigate the influence of normal insulin levels on levels of the insulin-like growth factor binding protein-1 (IGFBP-1) we measured this peptide postabsorptively and during hyperglycemic clamp in 17 healthy subjects, nine with low insulin response (LIR) and eight with high insulin response (HIR). The study was performed before and after 60 hours of treatment with dexamethasone 6 mg/d. The fasting levels of IGFBP-1 were significantly higher in LIR, 36 +/- 2.5 micrograms/L, than in HIR, 22 +/- 2.6 micrograms/L (P less than .01), while no differences in glucose, insulin, and C-peptide concentrations were found. Dexamethasone induced an increase in basal concentrations of insulin, while IGFBP-1 levels decreased to 18.8 +/- 2 micrograms/L in LIR (P less than .01) and to 14.0 +/- 0.9 micrograms/L in HIR (P less than .05). There was no correlation between the individual basal IGFBP-1 concentrations and basal insulin levels. In contrast, basal levels of IGFBP-1 were inversely correlated to the integrated insulin or C-peptide concentrations during the hyperglycemic clamp both before (r = -.67, P less than .01) and during dexamethasone (r = -.79, P less than .001). Dexamethasone, which increased the insulin resistance, did not change the relationship between basal IGFBP-1 and the glucose-induced insulin release. In conclusion, the morning levels of IGFBP-1 in healthy subjects reflect the acute beta-cell responsiveness to glucose, which may correspond to integrated diurnal insulin levels. The inhibitory effects of dexamethasone on the morning levels of IGFBP-1 can be explained by attendant hyperinsulinemia.     

Short-term effect of buformin, a biguanide, on insulin sensitivity, soluble fraction of tumor necrosis factor receptor and serum lipids in overweight patients with type 2 diabetes mellitus

AIMS/HYPOTHESIS: The UK Prospective Diabetes Study (UKPDS) showed that biguanide therapy in overweight patients reduced the risk for any diabetes-related endpoint and all-cause mortality. Biguanides lower the blood glucose values without stimulation of insulin release. We have investigated the short-term effect of buformin on insulin sensitivity, solved tumor necrosis factor receptors (sTNFRs), and serum lipids in overweight subjects with type 2 diabetes mellitus (DM). METHOD: Thirteen overweight subjects with type 2 DM were examined. The subjects who were fed 20 kcal/kg body weight were divided into two subgroups according to whether they were treated by buformin (Buformin group), or dietary therapy alone (Diet group). Six patients were in Buformin group and seven patients were in Diet group. We calculated insulin-mediated glucose uptake by the liver and peripheral tissues using euglycemic hyperinsulinemic clamp combined with an oral glucose load before and after buformin treatment or diet therapy for 2 weeks. RESULTS: Fasting plasma glucose, total cholesterol (T-chol), LDL-cholesterol (LDL-chol), and sTNFR2 were significantly decreased, and hepatic glucose uptake significantly increased from 32 +/- 7 to 42 +/- 7% (P < 0.05) in Buformin group but did not changed significantly in Diet group. However, the glucose infusion rate thought to express insulin sensitivity in peripheral tissue, TNF-alpha, sTNFR1, fasting plasma insulin, C-peptide, and NEFA levels did not change significantly in both the groups after treatment. CONCLUSION/INTERPRETATION: Buformin improved insulin sensitivity in the liver and decreased T-chol, LDL-chol, and sTNFR2. The mechanism of action for buformin likely involves inhibition of TNF-alpha. Buformin lowers insulin resistance and risk factors for cardiovascular disease including serum lipid and will therefore, be useful in management of overweight type 2 DM patients.     

Urinary excretion rate of C-peptide in fed and fasted obese humans

The aim of the study was to evaluate the reliability of urinary excretion rate of C-peptide as a marker of B-cell function during fasting. Ten obese subjects of both sexes fasted for 5 days. Diurnal serum C-peptide was collected before and on the 5th day; morning serum samples (for glucose, insulin and C-peptide) and 12-h urine samples (7.00 to 19.00 h) were collected daily. Body weight decreased from 138.7 +/- 15.9 to 132.9 +/- 15.6 kg. Morning glucose, insulin (-40%) and C-peptide (-50%) fell significantly throughout the study. Mean diurnal C-peptide values were 2.19 +/- 0.69 nmol/l before and 0.60 +/- 0.19 nmol/l after fasting (P less than 0.0001) and its secretion rate was 909.4 +/- 297.9 and 244.4 +/- 83.9 nmol/12 h (P less than 0.005), respectively. Excretion rate of C-peptide fell progressively from basal (11.2 +/- 4.2 nmol/12 h) to a nadir value of 1.3 +/- 0.8 nmol/12 h (P less than 0.0005); similarly, the C-peptide to creatinine clearance ratio fell from 0.062 +/- 0.035 to 0.028 +/- 0.015 (P less than 0.05). These results indicate that fasting modifies renal metabolism of C-peptide thus creating several complications in the quantitative interpretation of urinary levels as an index of its secretion rate from the B-cell.     

Elevated insulin, norepinephrine, and neuropeptide Y in hypertension

To investigate the relationship between insulin and sympathetic activity, plasma norepinephrine, neuropeptide Y, serum glucose and insulin concentrations were measured in ten age-, weight-, and sex-matched normotensive and untreated hypertensive subjects at fasting and 2 h following ingestion of a 75 g oral glucose dose. Hypertensives had higher fasting serum insulin (27 +/- 6 v 12 +/- 2 microU/mL; P = .02) and plasma norepinephrine (356 +/- 38 v 235 +/- 35 pg/mL; P = .03) concentrations than normotensives. Glucose load increased serum insulin (P less than .001) and plasma norepinephrine concentrations (P = .001) in both groups and hypertensives had still higher postglucose insulin (P = .003) and norepinephrine levels (P = .003) than normotensives. Fasting neuropeptide Y was higher in hypertensives than in normotensives (P = .03) and correlated with age in both groups (r = 0.7; r = 0.77). Postglucose serum insulin correlated positively with plasma norepinephrine (r = 0.75; P = .013) in normotensives, but these parameters correlated negatively in hypertensives (r = -0.7; P = .036). We hypothesize that elevated plasma norepinephrine and neuropeptide Y levels reflect an increased level of sympathetic nervous activity in hypertensives, which in turn may be responsible for the abnormal relationship between plasma NE and insulin levels.     

Meal-induced 24-hour profile of circulating glycated insulin in type 2 diabetic subjects measured by a novel radioimmunoassay

Increasing evidence supports a role for glycated insulin in the insulin-resistant state of type 2 diabetes. We measured 24-hour profiles of plasma glycated insulin, using a novel radioimmunoassay (RIA), to evaluate the effects of meal stimulation and intermittent fasting on circulating concentrations of plasma glycated insulin in type 2 diabetes. Patients (n = 6; hemoglobin A(1c) [HbA(1c)], 7.2% +/- 0.6%; fasting plasma glucose, 7.4 +/- 0.7 mmol/L; body mass index [BMI], 35.7 +/- 3.5 kg/m(2); age, 56.3 +/- 4.4 years) were admitted for 24 hours and received a standardized meal regimen. Half-hourly venous samples were taken for plasma glycated insulin, glucose, insulin, and C-peptide concentrations between 8 am and midnight and 2-hourly overnight. The mean plasma glycated insulin concentration over 24 hours was 27.8 +/- 1.2 pmol/L with a mean ratio of insulin:glycated insulin of 11:1. Circulating glucose, insulin, C-peptide, and glycated insulin followed a basal and meal-related pattern with most prominent increments following breakfast, lunch, and evening meal, respectively. The mean concentrations of glycated insulin during the morning, afternoon, evening, and night-time periods were 24.4 +/- 2.5, 28.7 +/- 2.3, 31.1 +/- 2.1, and 26.2 +/- 1.5 pmol/L, respectively, giving significantly higher molar ratios of insulin:glycated insulin of 18.0:1, 14.2:1, and 12.7:1 compared with 7.0:1 at night (P <.01 to P <.001). These data demonstrate that glycated insulin circulates at relatively high concentrations in type 2 diabetes with a diurnal pattern of basal and meal-stimulated release. A higher proportion of glycated insulin circulates at night suggestive of differences in metabolic clearance compared with native insulin.     

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 exogenous insulin on C-peptide levels in subjects with type 2 diabetes

Aim:The aim of this study was to determine whether the influence of insulin therapy on fasting and stimulated C-peptide levels in type 2 diabetic subjects is due to plasma glucose reduction or a direct effect of exogenous insulin.Methods:Plasma glucose and serum C-peptide levels were determined before and after IV injection of 1 mg glucagon on three separate days in 21 type 2 diabetic subjects. Day 1: without pharmacological treatment and fasting plasma glucose >11.1 mmol/L; day 2: fasting plasma glucose 4.4–7.8 mmol/L, 1 h after withdrawing intravenous regular insulin infusion; day 3: fasting plasma glucose 4.4–7.8 mmol/L with bed-time NPH insulin.Results:Fasting and glucagon stimulated C-peptide levels were higher on day 1 than days 2 and 3. Fasting, but not stimulated C-peptide levels, were lower on day 3 than day 2. These differences were not appeared when the percentage of C-peptide increment or the C-peptide/glucose ratio were compared in the three days.Conclusions:Blood glucose reduction instead of exogenous insulin is responsible for the C-peptide decrease during insulin therapy in type 2 diabetic subjects.     

Insulin and C-peptide plasma levels in patients with severe chronic pancreatitis and fasting normoglycemia

The aim of the present study was to evaluate insulin secretion by the pancreatic B cell in a group of patients with severe chronic pancreatitis and without overt diabetes. For this purpose we have measured plasma insulin and C-peptide peripheral levels in the fasting state and after a 100-g oral glucose load in 10 patients with severe chronic pancreatitis and fasting normoglycemia, and in 10 sex-, age-, and weight-matched healthy controls. As compared to normal subjects, patients with chronic pancreatitis showed: (1) significantly higher plasma glucose levels after oral glucose load (area under the plasma glucose curve 1708 +/- 142 vs 1208 +/- 47 mmol/liter X 240 min, P less than 0.005); (2) plasma insulin levels significantly higher at fasting (0.11 +/- 0.008 vs 0.08 +/- 0.005 nmol/liter, P less than 0.01) but not after oral glucose administration (area under the plasma insulin curve 79 +/- 12 vs 88 +/- 16 nmol/liter X 240 min); (3) significantly lower plasma C-peptide concentrations both in the fasting state (0.15 +/- 0.01 vs 0.54 +/- 0.05 nmol/liter, P less than 0.001) and after oral glucose load (area under the plasma C-peptide curve 211 +/- 30 vs 325 +/- 37 nmol/liter X 240 min, P less than 0.05). The finding of diminished plasma C-peptide levels suggests that chronic pancreatitis is associated with an impaired B-cell function even in the absence of overt diabetes. The increased or unchanged plasma insulin levels in spite of decreased plasma C-peptide concentrations indicate that in chronic pancreatitis insulin metabolism is reduced, most likely within the liver.     

One month's insulin treatment of type II diabetes: the early and medium-term effects following insulin withdrawal

In order to see if subcutaneous insulin treatment of type II diabetes might produce lasting physiologic changes, ten patients received one month's insulin treatment under strict dietary supervision. When compared to the pretreatment period, 48 hours after discontinuing insulin treatment fasting plasma glucose had fallen (P = 0.005), fasting serum insulin had risen (P = 0.005), and fasting hepatic glucose production measured by 3H-3-glucose turnover had fallen (P = 0.008). The metabolic clearance rate of glucose measured with the glucose clamp rose significantly after treatment at insulin infusion rates of 40 mU m-2 min-1 (P = 0.015) and 400 mU m-2 min-1 (P = 0.012). The serum insulin and C-peptide responses to oral glucose improved after the treatment in association with the improvement in glucose tolerance, but the plasma glucose response was unchanged. Six other type II diabetic patients who received only dietary supervision did not show significant changes in these variables. Six weeks after discontinuing insulin, the patients' fasting hepatic glucose production was still reduced compared to pretreatment (P = 0.028) and insulin action was still improved at both the lower (P = 0.028) and the higher (P = 0.028) insulin infusion rates, but the fasting plasma glucose and insulin and C-peptide responses to oral glucose had returned to pretreatment values. The improvement in glucose tolerance and beta-cell function induced by insulin treatment seems to be of more limited duration than the improvements in basal hepatic glucose production and in insulin action.     

Secretion and hepatic extraction of insulin after weight loss in obese noninsulin-dependent diabetes mellitus

We assessed the effects of weight loss on pancreatic secretion and hepatic extraction of insulin in 11 obese subjects with noninsulin-dependent diabetes mellitus. Weight loss of 15.4 +/- 2.0 kg (mean +/- SE) resulted in decreased fasting insulin [20.2 +/- 2.5 to 9.8 +/- 2.5 microU/mL (145 +/- 18 to 70 +/- 18 pmol/L); P less than 0.02] and C-peptide (850 +/- 80 to 630 +/- 110 pmol/L; P less than 0.05) levels. The plasma glucose response to oral glucose and iv glucagon was improved with unchanged peripheral insulin levels. When plasma glucose levels were matched to those before weight loss, peripheral serum insulin and plasma C-peptide responses to iv glucagon were increased and similar to those in obese nondiabetic subjects studied at euglycemia. The total insulin response (area under the curve) to iv glucagon was reduced 30% (P less than 0.005), while the total C-peptide response area did not change after weight loss. At matched hyperglycemia, the total response area was enhanced 72% for insulin (P less than 0.002) and 64% for C-peptide (P less than 0.001). Incremental (above basal) response areas after weight loss did not change for insulin, but increased 66% for C-peptide (P less than 0.05). The incremental areas were augmented nearly 2-fold (196%) for insulin (P less than 0.01) and 1.7-fold (173%) for C-peptide (P less than 0.01) when assessed at matched hyperglycemia. Both basal (7.3 +/- 0.5 to 14.1 +/- 1.8; P less than 0.01) and total stimulated (6.1 +/- 0.4 to 8.8 +/- 1.4; P less than 0.05) C-peptide to insulin molar ratios increased after weight loss. We conclude that after weight loss in noninsulin-dependent diabetes mellitus, 1) insulin secretion is decreased in the basal state but increased after stimulation; 2) changes in insulin secretion are reflected by peripheral levels of C-peptide but not insulin, due in part to enhanced hepatic insulin extraction; and 3) at matched levels of hyperglycemia insulin secretion is markedly increased and similar to that in obese nondiabetic subjects studied at euglycemia.     

Insulin and C-peptide responses to 75 g oral glucose load in the healthy man

Plasma insulin and C-peptide levels in the fasting state and after a 2-h 75 g oral glucose tolerance test (OGTT) in a large number of healthy subjects are reported. 247 volunteers (134 males, 113 females), aged 13-69 years, who had a negative history of diabetes, no history of significant disease, normal physical examination, normal body weight, normal glucose tolerance, normal blood tests, and who were taking no drugs were studied. Results, mean +/- SEM (range): fasting glucose concentration = 4.64 +/- 0.03 mmol/l (3.10 - 6.10), 1-h glucose concentration = 5.23 +/- 0.10 mmol/l (2.20 - 9.90), 2-h glucose concentration = 4.11 +/- 0.06 mmol/l (2.00 - 6.80); fasting insulin level = 0.088 +/- 0.002 nmol/l (0.03 - 0.28), 1-h insulin level = 0.45 +/- 0.01 nmol/l (0.06 - 1.63), 2-h insulin level = 0.24 +/- 0.01 nmol/l (0.05 - 1.12); fasting C-peptide concentration = 0.60 +/- 0.01 nmol/l (0.14 - 1.34), 1-h C-peptide concentration = 2.17 +/- 0.05 (0.63 - 8.56), 2-h C-peptide concentration = 1.77 +/- 0.04 nmol/(0.35 - 5.74). Fasting insulin and fasting C-peptide concentrations correlated to post-glucose insulin and C-peptide concentrations, respectively. At each sampling-point insulin concentration correlated to C-peptide concentration. After glucose ingestion, both insulin and C-peptide plasma levels correlated significantly with the corresponding glucose levels. During fasting, C-peptide but no insulin level correlated to glucose level.(ABSTRACT TRUNCATED AT 250 WORDS)     

Association between the metabolic syndrome and serum cortisol in overweight Latino youth

OBJECTIVE: The purpose of this report is to investigate the associations between metabolic syndrome (MS) and levels of morning serum cortisol in a cohort of overweight Latino youth. DESIGN: Subjects were 205 overweight, Latino youth (age 8-13 yr, body mass index percentile > 85, family history positive for type 2 diabetes). Measures included body composition by dual-energy x-ray absorptiometry, intraabdominal adipose tissue (IAAT) by magnetic resonance imaging, insulin sensitivity by frequently sampled iv glucose tolerance test/minimal model, fasting lipids, and serum cortisol. RESULTS: Children with MS had higher body mass index percentile, total body fat mass, and IAAT and lower insulin sensitivity than those without MS. Children with MS had higher morning serum cortisol levels, whether unadjusted (10.1 +/- 3.7 vs. 9.0 +/- 2.8 microg/dl, P < 0.05) or after adjusting for age, gender, total body fat and lean tissue mass, and insulin sensitivity (10.4 +/- 0.4 vs. 8.9 +/- 0.3 microg/dl, P < 0.01). Increasing number of features of MS was associated with higher cortisol levels, after adjusting for covariates (P = 0.001). Among individual features of MS, systolic blood pressure had the strongest relationship with adjusted cortisol level (r = 0.34; P < 0.001), followed by diastolic blood pressure and fasting plasma glucose (both r = 0.23; P < 0.01). IAAT was associated with cortisol (r = 0.16; P < 0.05), whereas high-density lipoprotein, triglycerides, and waist circumference were not. CONCLUSIONS: In overweight, Latino youth, MS is associated with higher morning serum cortisol levels, independent of body fat and insulin sensitivity. More studies are needed to investigate the role of relative hypercortisolism and chronic stress in obesity-related metabolic disorders in children.     

Relationships between insulin secretion, insulin metabolism and insulin resistance in mild glucose intolerance

The aim of this study was to evaluate whether the correlation between insulin resistance and peripheral hyperinsulinaemia existing in mild glucose intolerance corresponds to a relationship between insulin resistance and insulin overproduction by the pancreas. In addition, the possibility that insulin resistance is related to insulin metabolism was examined. Twenty five subjects with fasting normoglycaemia and an abnormal glucose response to the oral glucose tolerance test (OGTT) were studied. Insulin secretion by the pancreas was estimated by means of fasting C-peptide levels in peripheral blood. Insulin resistance was estimated by the rate of glucose disappearance from plasma after i.v. insulin injection. Insulin metabolism was estimated indirectly by the C-peptide: insulin molar ratio. A negative correlation was found between the glucose disappearance rate from plasma after i.v. insulin injection and fasting insulin levels (r = -0.677, p less than 0.001), but not fasting C-peptide concentrations (r = -0.164, p = NS). Glucose disappearance rate from plasma correlated positively with the C-peptide: insulin molar ratio (r = 0.626, p less than 0.001). These results suggest that in mild glucose intolerance insulin resistance and insulin secretion by the pancreas are not related phenomena, and that the defect responsible for insulin resistance might also be implicated in the impaired insulin metabolism.     

Relationship between insulin resistance, insulin secretion and insulin metabolism in simple obesity

The study was designed to evaluate whether the correlation occurring in simple obesity between insulin resistance and peripheral hyperinsulinemia corresponds to a relationship between insulin resistance and insulin overproduction by the pancreas. In addition, the study investigated the relation existing in simple obesity between insulin resistance and insulin metabolism. For these purposes, we measured and correlated: (1) insulin sensitivity, estimated by glucose disappearance rate from plasma after intravenous insulin injection; (2) insulin secretion by the pancreas, estimated by fasting C-peptide levels in peripheral blood; (3) insulin metabolism, estimated by means of C-peptide: insulin molar ratio in peripheral blood. Twenty-five subjects (20 females, five males) aged 21 to 59 years were studied. All were obese and had a normal glucose tolerance. Glucose disappearance rate from plasma after i.v. insulin injection averaged 3.65 +/- 0.42 mg/dl/min (mean +/- s.e.m.). Fasting C-peptide was 0.90 +/- 0.09 nmol/l. Fasting C-peptide: insulin molar ratio averaged 5.94 +/- 0.48. Negative correlations were found between glucose disappearance rates after i.v. insulin injection, ie, insulin sensitivity, and fasting concentrations of both insulin (r = -0.806, P less than 0.001) and C-peptide (r = -0.525, P less than 0.01). A positive relationship was found between glucose disappearance rate from plasma after i.v. insulin injection and fasting C-peptide: insulin molar ratio, ie, insulin metabolism (r = 0.707, P less than 0.001). We conclude that in simple obesity insulin overproduction by the pancreas is negatively related to insulin resistance, and insulin resistance and impaired insulin metabolism are strictly related phenomena.