Glucose Load In Patients Research Articles

Factors Influencing Glucose Response to Exercise Following Oral Glucose Load

PURPOSE: Exercise can reduce postprandial hyperglycemia by increasing contraction-mediated glucose uptake in skeletal muscles. However, postprandial exercise does not always have similar effects in all patients. This study aimed to analyze the factors influencing glucose response to exercise following oral glucose load.METHODS: We enrolled 169 adults with impaired glucose tolerance (IGT, n = 64) and type 2 diabetes (T2D, n = 105). We measured fingertip capillary blood glucose level at 30-minute intervals over 2-hour after the 75-g oral glucose ingestion. In addition, a single bout of moderate-intensity aerobic exercise was conducted at 30 minutes after 75-g oral glucose ingestion. We also measured glycated hemoglobin (HbA1c), insulin, insulin resistance (HOMA-IR), β-cell function (HOMA-β), physical activity level questionnaire and anthropometrics.RESULTS: There was a significant difference in glucose concentration between the IGT and T2D groups (<i>p</i> <.001). Additionally, we found that patients with short diabetes duration (≤1 year) had significantly more decrease in glucose concentration than long diabetes duration (≥10 years) (<i>p</i> <.001). A regression analysis showed that waist circumference, visceral fat area, fasting glucose, HbA1c, and HOMA-IR affected glucose response to exercise following oral glucose load in patients with T2D.CONCLUSIONS: Higher volumes of exercise following an oral glucose load may be necessary for individuals with Type 2 Diabetes (T2D) who have a longer disease duration, larger waist circumference, increased visceral fat area, higher HbA1c levels, and elevated HOMA-IR values in order to prevent hyperglycemia.

Various cut-off points for paradoxical increase of growth hormone after glucose load in patients with acromegaly and their clinical implications

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Impact of oral anticholinergic on insulin response to oral glucose load in patients with impaired glucose tolerance.

Background:Preliminary data indicates there is a cholinergic basis to insulin secretion.Aims & Objective:To investigate the impact of oral anticholinergics on insulin secretion in subjects with impaired glucose tolerance (IGT), in comparison with volunteers having normal glucose tolerance (NGT). Material & Methods: This prospective observational study recruited 10 IGT and 10 NGT subjects. An oral glucose tolerance test (OGTT) was conducted twice in the absence and presence of hyoscine butyl-bromide (HBB). The plasma glucose (PG) and insulin levels were serially estimated at 30-min increments for 2 h after the OGTT. Early (ΔI30/ΔPG30) & late (insulin/PGAUC 60-120) phase insulin activity were assessed subsequently.Results:The study constituted of 10 IGT (4M/6F, BMI: 28.80 ± 2.30) and 10 NGT (5M/5F, BMI: 23.00 ± 0.80) subjects. In the NGT group, the pre-HBB mean glucose levels (0-120 min) were comparable with those recorded after HBB intake. However, after HBBB, the mean insulin levels decreased significantly at t = 90 and 120min, confirmed by attenuated late phase insulin activity in IGT (P = 0.023) & NGT (P = 0.006) group. On the other hand, in the IGT group, however, HBB did not impact on the mean PG and insulin levels (0-120 min).Conclusions:Our study findings indicate that insulin secretion is influenced by cholinergic system and that oral anticholinergics may attenuate the late phase insulin activity in varying degrees of glycemic status.

Impaired counterregulatory responses to hypoglycaemia following oral glucose in adults with cystic fibrosis.

The aim of this study was to determine the mechanism(s) for hypoglycaemia occurring late following oral glucose loading in patients with cystic fibrosis (CF). A 3h 75g OGTT was performed in 27 non-diabetic adults with CF who were classified based on this test as experiencing hypoglycaemia (glucose <3.3mmol/l with or without symptoms or glucose <3.9mmol/l with symptoms, n = 14) or not (n = 13). Beta cell function, incretin (glucagon-like peptide-1 [GLP-1] and glucose-dependent insulinotropic peptide [GIP]) and counterregulatory hormone responses (glucagon, catecholamines, growth hormone and cortisol) were assessed. The two groups did not differ in age, weight or BMI. There were more male participants and individuals with pancreatic exocrine insufficiency in the hypoglycaemia group. Fasting plasma glucose did not differ between the two groups (5.3 ± 0.16 vs 5.3 ± 0.10mmol/l). Both fasting insulin (20.7 ± 2.9 vs 36.5 ± 4.8pmol/l; p = 0.009) and C-peptide (0.38 ± 0.03 vs 0.56 ± 0.05nmol/l; p = 0.002) were lower in those who experienced hypoglycaemia. Following glucose ingestion, glucose concentrations were significantly lower in the hypoglycaemia group from 135min onwards, with a nadir of 3.2 ± 0.2 vs 4.8 ± 0.3mmol/l at 180min (p < 0.001). The test was terminated early in three participants because of a glucose level <2.5mmol/l. Insulin and C-peptide concentrations were also lower in the hypoglycaemia group, while incretin hormone responses were not different. Modelling demonstrated that those experiencing hypoglycaemia were more insulin sensitive (439 ± 17.3 vs 398 ± 13.1mlmin-1m-2, p = 0.074 based on values until 120min [n = 14]; 512 ± 18.9 vs 438 ± 15.5mlmin-1m-2, p = 0.006 based on values until 180min [n = 11]). In line with their better insulin sensitivity, those experiencing hypoglycaemia had lower insulin secretion rates (ISRfasting: 50.8 ± 3.2 vs 74.0 ± 5.9pmolmin-1m-2, p = 0.002; ISROGTT: 44.9 ± 5.0 vs 63.4 ± 5.2nmol/m2, p = 0.018) and beta cell glucose sensitivity (47.4 ± 4.5 vs 79.2 ± 7.5pmolmin-1m-2 [mmol/l]-1, p = 0.001). Despite the difference in glucose concentrations, there were no significant increases in glucagon, noradrenaline, cortisol or growth hormone levels. Adrenaline increased by only 66% and 61% above baseline at 165 and 180min when glucose concentrations were 3.8 ± 0.2 and 3.2 ± 0.2mmol/l, respectively. Hypoglycaemia occurring late during an OGTT in people with CF was not associated with the expected counterregulatory hormone response, which may be a consequence of more advanced pancreatic dysfunction/destruction.

Distinct response of fat and gastrointestinal tissue to glucose in gestational diabetes mellitus and polycystic ovary syndrome.

Gestational diabetes mellitus (GDM) and polycystic ovary syndrome (PCOS) are distinct pathologies with impaired insulin sensitivity as a common feature. The aim of this study was to evaluate the response of fat tissue adipokines and gastrointestinal incretins to glucose load in patients diagnosed with one of the two disorders and to compare it with healthy controls. Oral glucose tolerance test (oGTT) was performed in 77 lean young women: 22 had positive history of GDM, 19 were PCOS patients, and 36 were healthy controls. Hormones were evaluated in fasting and in 60 min intervals during the 3 h oGTT using Bio-Plex ProHuman Diabetes 10-Plex Assay for C-peptide, ghrelin, GIP, GLP1, glucagon, insulin, leptin, total PAI1, resistin, visfatin and Bio-Plex ProHuman Diabetes Adipsin and Adiponectin Assays (Bio-Rad). Despite lean body composition, both PCOS and GDM women were more insulin resistant than controls. Significant postchallenge differences between the GDM and PCOS groups were observed in secretion of adipsin, leptin, glucagon, visfatin, ghrelin, GIP, and also GLP1 with higher levels in GDM. Conversely, PCOS was associated with the highest resistin, C-peptide, and PAI1 levels. Our data suggest that decreased insulin sensitivity observed in lean women with GDM and PCOS is associated with distinct hormonal response of fat and gastrointestinal tissue to glucose load.

Factors associated with fibroblast growth factor 19 increment after oral glucose loading in patients who were previously admitted for coronary angiography

BackgroundWe investigated factors associated with fibroblast growth factor 19 (FGF-19) increment after oral glucose loading (OGL) in human subjects. MethodsA total of 240 outpatients without known diabetes who were previously admitted for coronary angiography underwent an oral glucose tolerance test. FGF-19 increment (pg/ml) was calculated as FGF-19 2h after OGL minus fasting FGF-19. ResultsOverall, FGF-19 significantly increased after OGL (from 123 [78–201] to 141 [80–237], p=0.001). By age tertiles (≦54, 55–64, ≧65), FGF-19 significantly increased only in patients aged ≧65 (from 143 [98–209] to 189 [124–332], p<0.001). By glucose regulation status, FGF-19 significantly increased in patients with normal glucose tolerance (from 117 [78–211] to 153 [106–325], p=0.014) and in patients with prediabetes (from 117 [73–179] to 123 [70–204], p=0.043), but not in patients with diabetes (from 181 [102–243] to 178 [111–275], p=0.139). FGF-19 significantly increased in patients on statin treatment (from 120 [78–207] to 145 [86–264], p<0.001), but not in patients not on statin therapy (from 125 [86–196] to 128 [68–230] pg/ml, p=0.676). These findings remained significant after adjustment for confounders. ConclusionsFGF-19 increment after OGL was positively associated with age, and negatively associated with abnormal glucose regulation and statin treatment.

Alteration in glucose metabolism after an oral glucose load in patients with non-alcoholic fatty liver disease

Alteration in glucose metabolism after an oral glucose load in patients with non-alcoholic fatty liver disease

Metformin reduces vascular endothelial dysfunction caused by an acute glucose load in patients with hypertension

Background. To investigate the effects of a single dose of metformin (MF) on endothelium-dependent vasodilatation and serum antioxidant and free fatty acid levels in patients with primary hypertension (PH) after an acute glucose load. Materials and methods. Patients with untreated PH were randomized to a no-metformin group (PH, n = 34) and a metformin group (PH+ MF, n = 28) who received a single dose of 500 mg metformin before testing. Healthy volunteers (n = 31) served as a control group. Brachial artery endothelium-dependent flow-mediated vasodilatation (FMD) was determined at 0, 1, 2 and 3 h after glucose load. Levels of serum superoxide dismutase (SOD), total antioxidant capacity (T-AOC), anti-superoxide anion free radical (AntiO2) and free fatty acids (FFA) were measured. Results. The FMD in the PH group decreased significantly 1 h after glucose load (PH: 10.9 ± 2.9% vs 13.67 ± 3.42% before glucose load). Metformin inhibited the effects of glucose load on FMD. At 1 h after acute glucose load, the concentrations of SOD, T-AOC and AntiO2 in the PH group decreased significantly compared with their fasting levels, and metformin inhibited the acute glucose load-induced decline in SOD and T-AOC levels. Conclusions. Metformin can prevent transient endothelial dysfunction caused by acute glucose load in patients with PH.

Quercetin Dampens Postprandial Hyperglycemia in Type 2 Diabetic Patients Challenged with Carbohydrates Load

Postprandial hyperglycemia is a major risk factor for diabetic co mp licat ions leading to disabilities and mortality in diabetics. Quercetin, a flavonoid, has been tried in trad itional med icine for treat ing many disorders including diabetes. The present study was designed to evaluate the potential of quercetin to damp postprandial blood glucose level after maltose and glucose loading in patients with type 2 diabetes mellitus (DM). In a rando mized, b linded crossover study, single oral dose (400mg ) of quercetin or placebo formula was ad min istered to the patients 30 min before loading with either maltose (2g/kg) or g lucose (100g), blood samp les are taken at different intervals for measurement of plas ma g lucose. The results clearly showed amelio rated postprandial hyperglycemia due to the use of quercetin, it significantly dampened the postprandial hyperglycemia only after maltose loading compared to placebo; no effect reported for quercetin after glucose loading. In conclusion, quercetin effectively suppresses postprandial hyperglycemia in patients with type 2 DM loaded with maltose, which may be attributed to α-glucosidase inhibition.

Effect of bypassing the proximal gut on gut hormones involved with glycemic control and weight loss

BackgroundThe reported remission of type 2 diabetes in patients undergoing Roux-en-Y gastric bypass has brought the role of the gut in glucose metabolism into focus. Our objective was to explore the differential effects on glucose homeostasis after oral versus gastrostomy glucose loading in patients with Roux-en-Y gastric bypass at an academic health science center. MethodsA comparative controlled investigation of oral versus gastrostomy glucose loading in 5 patients who had previously undergone gastric bypass and had a gastrostomy tube placed in the gastric remnant for feeding. A standard glucose load was administered either orally (day 1) or by the gastrostomy tube (day 2). The plasma levels of glucose, insulin, glucagon-like peptide 1 and peptide YY were measured before and after glucose loading. ResultsExclusion of the proximal small bowel from glucose passage induced greater plasma insulin, glucagon-like peptide 1, and peptide YY responses compared with glucose loading by way of the gastrostomy tube (P <.05). ConclusionsExclusion of glucose passage through the proximal small bowel results in enhanced insulin and gut hormone responses in patients after gastric bypass. The gut plays a central role in glucose metabolism and represents a target for future antidiabetes therapies.

Safety Issues of Long-Term Glucose Load in Patients on Peritoneal Dialysis—A 7-Year Cohort Study

BackgroundEffects of long-term glucose load on peritoneal dialysis (PD) patient safety and outcomes have seldom been reported. This study demonstrates the influence of long-term glucose load on patient and technique survival.MethodsWe surveyed 173 incident PD patients. Long-term glucose load was evaluated by calculating the average dialysate glucose concentration since initiation of PD. Risk factors were assessed by fitting Cox's models with repeatedly measured time-dependent covariates.ResultsWe noted that older age, higher glucose concentration, and lower residual renal function (RRF) were significantly associated with a worse patient survival. We found that female gender, absence of diabetes, lower glucose concentration, use of icodextrin, higher serum high density lipoprotein cholesterol, and higher RRF were significantly associated with a better technique survival.ConclusionsLong-term glucose load predicted mortality and technique failure in chronic PD patients. These findings emphasize the importance of minimizing glucose load in PD patients.

Effects of saxagliptin on β-cell stimulation and insulin secretion in patients with type 2 diabetes

To study the effect of dipeptidyl peptidase-4 (DPP-4) inhibition with saxagliptin on β-cell function as reflected by the stimulated insulin secretion rate after an enteral glucose load in patients with type 2 diabetes. Patients in this randomized, parallel-group, double-blind, placebo-controlled study were drug-naïve, aged 43-69 years, with baseline haemoglobin A1c (HbA1c) 5.9-8.1%. Twenty patients received saxagliptin 5 mg once daily; 16 received placebo. Patients were assessed at baseline and week 12 by intravenous hyperglycaemic clamp (0-180 min, fasting state), and intravenous-oral hyperglycaemic clamp (180-480 min, postprandial state) following oral ingestion of 75 g glucose. Primary and secondary endpoints were percent changes from baseline in insulin secretion during postprandial and fasting states, respectively. Insulin secretion was calculated by C-peptide deconvolution. After 12 weeks, saxagliptin significantly increased insulin secretion percent change from baseline during the postprandial state by an 18.5% adjusted difference versus placebo (p = 0.04), an improvement associated with increased peak plasma concentrations of intact glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide. In the fasting state, saxagliptin significantly increased insulin secretion by a 27.9% adjusted difference versus placebo (p = 0.02). Saxagliptin also improved glucagon area under the curve in the postprandial state (adjusted difference -21.8% vs. placebo, p = 0.03). DPP-4 inhibition with saxagliptin improves pancreatic β-cell function in postprandial and fasting states, and decreases postprandial glucagon concentration. Given the magnitude of enhancement of the insulin response in the fasting state, further study into the effect of DPP-4 inhibition on the β-cell is warranted.

Bypass of the Proximal Gut Has Weight Loss Independent Effects on Glycemic Control

Introduction The reported remission of type 2 diabetes in patients undergoing Roux-en-Y gastric bypass has brought the role of the gut in glucose metabolism in focus. We aimed to explore the role of the proximal gut on glucose handling.Methods A comparative controlled investigation of oral versus gastrostomy glucose loading in patients who had previously undergone gastric bypass and had a gastrostomy tube in the gastric remnant for feeding. A standard glucose load was administered either orally (day 1) or via the gastrostomy tube (day 2). Plasma levels of glucose, insulin, glucagon-like peptide 1 (GLP-1) and peptide YY (PYY) were measured pre and post glucose loading. Results Exclusion of the proximal small gut from glucose passage induced lower plasma glucose responses and higher plasma insulin, GLP-1 and PYY responses compared to glucose via a gastrostomy (p<0.05). Conclusions Exclusion of glucose passage through the proximal small gut results in enhanced insulin and gut hormone responses and suggests a weight loss independent effect explaining the improved glycaemic control after gastric bypass. The gut plays a central role in glucose metabolism and represents a target for future antidiabetes therapies.

Multiple Factors Lead to a Low Referral Rate for Bariatric Surgery in an Urban Primary Care Setting

Introduction The reported remission of type 2 diabetes in patients undergoing Roux-en-Y gastric bypass has brought the role of the gut in glucose metabolism in focus. We aimed to explore the role of the proximal gut on glucose handling.Methods A comparative controlled investigation of oral versus gastrostomy glucose loading in patients who had previously undergone gastric bypass and had a gastrostomy tube in the gastric remnant for feeding. A standard glucose load was administered either orally (day 1) or via the gastrostomy tube (day 2). Plasma levels of glucose, insulin, glucagon-like peptide 1 (GLP-1) and peptide YY (PYY) were measured pre and post glucose loading. Results Exclusion of the proximal small gut from glucose passage induced lower plasma glucose responses and higher plasma insulin, GLP-1 and PYY responses compared to glucose via a gastrostomy (p<0.05). Conclusions Exclusion of glucose passage through the proximal small gut results in enhanced insulin and gut hormone responses and suggests a weight loss independent effect explaining the improved glycaemic control after gastric bypass. The gut plays a central role in glucose metabolism and represents a target for future antidiabetes therapies.

Delayed Response of Amylin Levels after an Oral Glucose Challenge in Children with Prader-Willi Syndrome

PurposeAmylin secretion is increased parallel to insulin in obese subjects. Despite their marked obesity, a state of relative hypoinsulinemia occurs in children with Prader-Willi syndrome (PWS). Based on the hypothesis that amylin levels may be relatively low in PWS children, contributing to their excessive appetite, we studied amylin levels after oral glucose loading in children with PWS and overweight controls.Materials and MethodsPlasma levels of amylin, glucagon, insulin, and glucose were measured at 0, 30, 60, 90, and 120 min after a glucose challenge in children with PWS (n = 18) and overweight controls (n = 25); the relationships among the variables were investigated in these two groups.ResultsAmylin levels were significantly correlated with insulin during fasting and during the oral glucose tolerance test in both groups. Amylin levels between 0 and 60 min after glucose loading were statistically different between the two groups. They were lower in children with PWS than in the controls between 0 and 30 min after glucose loading.ConclusionThe relatively low levels of amylin, compared to those in overweight controls, during the early phase of glucose loading in patients with PWS, may contribute, in part, to the excessive appetite of PWS patients as compared to the overweight controls.

Hyperglycemia and Hypoinsulinemia in Patients with Fanconi-Bickel Syndrome

To evaluate glucose and insulin responses to oral glucose load in patients with FBS. Ten children (7.3 ± 4.8 years) diagnosed with FBS in early infancy underwent a standard oral glucose tolerance test (OGTT); plasma glucose (PG) and serum insulin concentrations were measured at 30-min intervals for 2 hours. HbAtc, insulin-like growth factor-1, and fasting lipid profiles were also measured. Mean fasting and 2-h PG concentrations were 3.8 ± 0.9 mmoVI and 8.6 ± 3.0 mmol/1, respectively. 2-hour PG levels were above 11.1 mmolll in two patients (20%) and between 7.75 and 11.1 mmoVI in four patients (40%). HbAtc was normal in all the patients with a mean of 5.4 ± 0.3%. Mean fasting and peak serum insulin levels were 8. 7 ± 0.8 pmol/1 and 98.6 ± 43.0 pmoVI, respectively, and did not differ between / the patients with normal and abnormal OGTT. , Patients with abnormal OGTT were younger ( 4.8 ± 3.2 vs 11.0 ± 4.8 yr; p = 0.04). Fasting PG increased with age (r = 0.80, p <0.01). Total and LDL cholesterol as well as triglyceride concentrations were elevated. Most but not all patients with FBS have impaired glucose tolerance/diabetes range hyperglycemia after OGTT while maintaining normal HbAtc· Patients with FBS are relatively hypoinsulinemic. Both fasting hypoglycemia and post-OGTT hyperglycemia seem to improve with age.

EFFECT OF POST-GLUCOSE CHALLENGE ON LIPID PROFILE IN PATIENTS WITH TYPE 2 DIABETES.

Purpose Fasting samples are required for serum lipid measurement due to the concern of elevated triglycerides (TGs) from high-fat meals. Postprandial hypertriglyceridemia could also affect the low-density lipoprotein (LDL) cholesterol values routinely calculated based on the Freidewald equation. The effect of postprandial hyperglycemia mainly from carbohydrate on lipid profile is less clear, especially among diabetic patients. The purpose of this study was to determine the changes in serum lipid panel before and after a standard oral glucose loading in patients with type 2 diabetes. Methods A convenient sample of 50 diabetic patients with fasting blood glucose Results Twenty-four percent of the patients were smokers and 96% were males, with a mean age of 67 years, BMI 28.5 kg/m2, systolic BP 130 mm Hg, and HbA1c 7.4%. Sixty-eight percent of the patients were on statin, 68% on ACE-I/ARB, and 10% on insulin. The mean values of total cholesterol (TC), LDL cholesterol, high-density lipoprotein (HDL) cholesterol, and TGs before and after glucose challenge were 166, 92, 44, 154, and 162, 92, 40, 150 (mg/dL), respectively. The decrease in TC and HDL from baseline was statistically significant (p Conclusion In this elderly and predominantly male patient population from a VA primary care clinic, we found a significantly decreased TC and HDL levels associated with hyperglycemia from oral glucose challenge. Lipid management is one of the main treatment strategies for cardiovascular risk reduction in diabetic patients. Therefore, it is clinically important to have accurate measurement of all components of lipid profile. Although the exact mechanisms for the reduction in TC and HDL associated with postprandial hyperglycemia are unknown, a strict fasting blood sample without pretest carbohydrate intake is preferred for lipid panel analysis.

Comment on: Nathan DM, Buse JB, Davidson MB et al. (2006) Management of hyperglycaemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy. A consensus statement from the American Diabetes Association and the European Association for the Study of Diabetes. Diabetologia 49: 1711–1721

Glucose-responsive insulin secretion is frequently impaired prior to the onset of type 2 diabetes [1]. In addition, considering the reduced pancreatic beta cell mass in patients with type 2 diabetes [2], defects in insulin secretion appear heterogeneous in this patient group. In some patients, only postprandial insulin secretion appears impaired, whilst in others, basal insulin secretion is also affected. However, postprandial insulin secretion is impaired in almost all patients with type 2 diabetes. In the recently published consensus statement from the American Diabetes Association [3] and the European Association for the Study of Diabetes [4] concerning the initiation and adjustment of therapy for managing hyperglycaemia in type 2 diabetes, initial insulin therapy is aimed at increasing basal insulin supply with intermediateor long-acting insulins. Such a regimen cannot completely mimic a physiological pattern of insulin secretion. Consequently, postprandial glycaemic control tends to be inadequate, and a risk exists of fasting hypoglycaemia. Furthermore, the postprandial hyperglycaemia observed in patients with early-stage or mild type 2 diabetes increased the risk of microangiopathy or arteriosclerosis in two largescale clinical studies of type 2 diabetes, the United Kingdom Prospective Diabetes Study [5] and the DECODE study [6]. It has also been suggested that therapy focused on lowering postprandial glucose, rather than fasting glucose, may be superior for lowering HbA1c [7] and glucose variability (spike) [8]. Insulin preparations have been developed to provide insulin replacement that more closely reflects physiological insulin secretion; the introduction of rapid-acting insulin analogues and long-acting soluble insulin analogues has been a further step in this direction. Rapid-acting insulin analogues have been particularly effective at targeting postprandial hyperglycaemia [8]. They can, therefore, effectively reduce postprandial plasma glucose, even if administered immediately before a meal, and also minimise the risk of hypoglycaemia prior to the next meal [8]. The exact contribution of postprandial and fasting glucose increments to overall hyperglycaemia remains controversial. Monnier et al. reported that postprandial glucose excursion contributes up to ∼70% of the glucose load in patients with diabetes whose HbA1c levels are <7.3%, whereas the contribution of fasting hyperglycaemia increases gradually as diabetes worsens [9]. However, even in patients whose glycaemic control is poor, studies have demonstrated that treatment targeting postprandial hyperglycaemia, which improves glucose-responsive insulin secretion in patients with glucose desensitisation, improves both postprandial and also morning fasting plasma glucose (FPG) in such patients [10–12]. We hypothesised that mealtime dosing with rapid-acting insulin analogues strictly controls postprandial and daytime plasma glucose levels, and thereby improves glucose desensitisation and glucose-responsive insulin secretion. To test these hypotheses, we recently evaluated the effect of a mealtime, rapid-acting insulin analogue on the minimum early morning FPG levels (nadir FPG) in 40 Japanese Diabetologia (2007) 50:229–230 DOI 10.1007/s00125-006-0524-9

Changes in bioactive IGF-I and IGF-binding protein-1 during an oral glucose tolerance test in patients with liver cirrhosis

Liver cirrhosis is characterized by reduced circulating IGF-I and this has been linked to an adverse clinical outcome. Therefore, we investigated the dynamic changes in circulating total, free, and bioactive IGF-I, IGF-binding protein (IGFBP)-1, IGFBP-2, and IGFBP-1-bound IGF-I (binary complex) during an oral glucose tolerance test (OGTT) in patients with liver cirrhosis. Seven Caucasian males with liver cirrhosis and seven healthy males matched for age (54.4+/-3.2 vs 54.6+/-4.4 years) and body mass index (25.3+/-1.2 vs 25.9+/-1.3 kg/m2) were studied. Blood samples were drawn at 0, 30, 60, 90, 120, 150, and 180 min for determination of serum total and free IGF-I, IGFBP-1, IGFBP-2, and binary complex, while bioactive IGF-I was measured at 0, 30, 60, 120, and 180 min. In comparison with healthy subjects, baseline levels of total (47%), free (36%), and bioactive IGF-I (51%) were lower, while IGFBP-1 (268%) was higher (P<0.05), IGFBP-2 (172%) tended to be higher (P>0.05), and the binary complex unchanged (approximately 100%) in cirrhotic patients. Serum total and free IGF-I, and IGFBP-2 remained unchanged in both study groups during the OGTT. Bioactive IGF-I decreased by 29% from baseline to 60 min in cirrhotic patients and remained low at the end of the OGTT (P<0.05). A similar tendency was observed in healthy controls (P=0.052). Concomitantly, IGFBP-1, binary complex, and IGFBP-1 saturation index decreased significantly in both groups. The disappearance of the binary complex was about twofold faster than that of IGFBP-1 (P < 0.05). Despite unchanged concentrations of total and free IGF-I, bioactive IGF-I declined significantly after an oral glucose load in patients with liver cirrhosis and the same tendency was observed in healthy subjects. We speculate that the reduction in bioactive IGF-I may be related to the higher levels of free IGFBP-1 and the faster disappearance of IGFBP-1-bound IGF-I.

Upper Body Obesity and Hyperinsulinemia Are Associated with Anovulation

The objective of this study was to determine the effect of body fat distribution and hyperinsulinemia on the occurrence of ovulation. Fifty-six women (20–35 years old) either with overweight or obesity (body mass index ≥25) were studied. They were classified in two groups according to waist/hip ratio (WHR); one with predominance of adiposity in the upper body segment (n = 29, WHR >0.85) and the other with predominant adiposity in the lower body segment (n = 27, WHR ≤0.85). Basal body temperature and serum progesterone were determined in each cycle during 6 months. Serum insulin levels were measured at baseline and 30, 60, 90, 120 and 180 min after a 75-gram oral glucose load. The mean insulin values in response to oral glucose load in patients with upper body segment obesity were significantly higher than those corresponding to women with lower body segment obesity. Furthermore, the ratio between ovulated cycles and all the cycles studied in patients with upper body segment obesity was significantly lower than that observed in patients with lower body segment obesity. Upper body obesity seems to affect the ovulatory process and this may be related to the presence of hyperinsulinemia.