2-hour Postprandial Glucose Levels Research Articles

Improvement of both fasting and postprandial glycemic control by the two-step addition of miglitol and mitiglinide to basal insulin therapy: a pilot study

BackgroundCombination therapy consisting of basal insulin and oral hypoglycemic agents (OHAs) is effective for the treatment of type 2 diabetes (T2DM) that cannot be adequately controlled using OHAs alone. Though basal insulin with metformin or sulfonylurea is an effective therapy, it cannot reduce postprandial glycemia without the risk of hypoglycemia. We examined a two-step regimen consisting of the addition of postprandial hypoglycemic agents (an alpha-glucosidase inhibitor and a glinide) in patients whose T2DM was poorly controlled using basal insulin therapy.MethodsInpatients between the ages of 30–79 years who had T2DM and an HbA1c level of more than 7.0% were recruited. The patients were treated with once-daily insulin glargine with or without metformin, depending on the patient’s age and renal function. Insulin glargine was titrated to achieve a target fasting glucose level of 70–130 mg/dL as a first step (STEP0). If the 2-hour postprandial glucose (PBG) level was higher than the target of 180 mg/dL, miglitol treatment (150 mg/day) was initiated, with dose adjustments (75–225 mg) allowed depending on abdominal symptoms and the PBG (STEP1). If the PBG of the patients remained higher than the target after 3 days of treatment, mitiglinide (30 mg/day, titrated up to 60 mg) was added (STEP2). We then evaluated the proportion of patients who achieved the target PBG before and after the two-step regimen. Continuous Glucose Monitoring (CGM) was performed throughout the two-step protocol in most of the patients.ResultsOf the 16 patients who were recruited (median age, 67.0 [58.0-71.0] years; body mass index, 25.0 [22.0-27.9] kg/m2; HbA1c level at admission, 9.1% [8.35-10.4%]), 1 patient (6.25%) achieved the target PBG at STEP 0 and 14 patients (87.5%) had achieved the target PBG at the end of the treatment protocol (P = 0.002). CGM showed a significant decrease in the glucose level at each step of the protocol. The standard deviations in the CGM glucose levels for 24 hours, MAGE, and M-value also improved.ConclusionsThe two-step addition of postprandial hypoglycemic agents to basal insulin therapy is potentially effective and safe for decreasing both the fasting and postprandial glucose levels.

A Randomized, Open-Label, Multicenter, 4-Week Study to Evaluate the Tolerability and Pharmacokinetics of ITCA 650 in Patients With Type 2 Diabetes

BackgroundExenatide, a glucagon-like peptide-1 receptor agonist administered by self-injection, decreases plasma glucose, glycosylated hemoglobin (HbA1c), and weight in patients with type 2 diabetes. ITCA 650 is an investigational new drug that provides continuous subcutaneous delivery of exenatide. ObjectiveThis randomized, open-label, multicenter, 28-day study evaluated the tolerability, pharmacodynamics, and pharmacokinetics of ITCA 650 in patients with type 2 diabetes. MethodsThe study enrolled patients with type 2 diabetes who were receiving a stable regimen of diet and exercise alone or a stable dose of metformin monotherapy, thiazolidinedione monotherapy, or metformin plus thiazolidinedione combination therapy. Patients were randomized to receive 10, 20, 40, or 80 μg/d of ITCA 650 placed subcutaneously for 28 days. Plasma glucose, HbA1c, insulin, and weight were measured at regular intervals throughout the study. Exenatide levels and anti-exenatide antibodies were also assessed. ResultsForty-four patients were randomized to treatment. From baseline to end point, significant (P < 0.05) decreases in fasting plasma glucose levels, 2-hour postprandial glucose levels, and glucose AUC curve were seen in all treatment groups. HbA1c levels also decreased significantly (P < 0.001) in all 4 treatment groups. Weight was significantly (P < 0.05) lowered in the 40- and 80-μg/d groups. Detectable levels of exenatide were noted within 12 to 24 hours of ITCA 650 placement, reached steady state by 24 hours, and then remained relatively steady during a plateau period until device removal on day 29. Exenatide levels declined to undetectable levels within 24 hours after removal of the ITCA 650. The most common adverse events were nausea, decreased appetite, and vomiting; these were transient and mostly mild or moderate in severity. Mild local adverse events related to the healing process were common at the placement site but abated after 1 week. Twelve patients developed anti-exenatide antibodies; however, the pharmacokinetics of ITCA 650 were not altered compared with those who did not develop antibodies. ConclusionsITCA 650 provided continuous and controlled subcutaneous delivery of exenatide for 28 days that was generally well tolerated and produced significant reductions in plasma glucose, HbA1c, and weight. Further studies are warranted to characterize the long-term tolerability and efficacy of ITCA 650 for the treatment of patients with type 2 diabetes. ClinicalTrials.gov identifier: NCT01798264.

Relationship between Fasting and 2-Hour Postprandial Plasma Glucose Levels and Vascular Complications in Patients with Type 2 Diabetes Mellitus

To investigate the relationship between fasting and 2-h postprandial plasma glucose concentrations and vascular complications in type 2 diabetes. Consecutive patients with type 2 diabetes admitted for blood glucose control were grouped according to their fasting and 2-h postprandial plasma glucose levels. Frequency and severity of diabetic retinopathy and nephropathy, number of carotid artery plaques, coefficient of variation of R-R intervals (CVRR), brachial-ankle pulse wave velocity (baPWV), intima-media thickness, brain natriuretic peptide level, ankle-brachial index, and high-sensitivity C-reactive protein levels were compared. In the 206 patients studied, mean±SD age, glycosylated haemoglobin and duration of diabetes were 63.4±13.7 years, 9.8±1.8% and 13.4±8.9 years, respectively. Patients with high fasting plasma glucose levels had a higher frequency of proliferative retinopathy than those with low fasting levels. Patients with medium or high 2-h postprandial plasma glucose levels had higher baPWV and lower CVRR, respectively, than those with low 2-h levels. There was an inverse correlation between baPWV and CVRR. Elevated fasting and postprandial plasma glucose levels are risk factors for vascular complications in type 2 diabetes mellitus.

Glycemic Profiles and Their Diagnostic Value among Inpatients in a Cardiology Clinic

Background: Most patients in cardiology clinics have diabetes mellitus (DM). Therefore, glucose monitoring is very important for these patients. Routinely, only fasting glucose is measured but not postprandial glucose and HbA1c; thus, the correlation between diabetes frequency and cardiac diagnosis in cardiology inpatients is unknown. The aim of this study was to determine the glucose abnormalities in inpatient cardiology clinics and their relationship with the diagnosis of heart disease. Material and method: 309 patients (107 F/202 M; mean age 63.4 ± 13 years) hospitalized in cardiology clinic between December 2009 and February 2010 was recruited to the study. Admission glucose level, body mass index (BMI), fasting glucose level after stabilization, 2-hour postprandial glucose levels, HbA1c and diagnosis were recorded for all subjects. Patients were evaluated as DM (+), DM (-), and new-onset DM. Cardiac diagnoses were classified as acute coronary syndrome (ACS) and others. Pre-diabetes was defined based on fasting/random glucose and HbA1c concentrations among the non-diabetic patients. Results: 108 (35%) of patients had DM, whereas 39 patients (12.6%) had unknown diabetes. Glucose profile of subjects with new-onset DM was similar to that of DM (+) patients. The remaining 162 patients (52.4%) were free of DM although 53 of them (32.7%) had prediabetes. Prediabetes was diagnosed in 17.1% of all patients. No difference was detected between ACS and Others regarding DM frequency. Admission/fasting glucose and HbA1c levels were found to be higher in ACS patients (p: 0.02). Prediabetic patients with ACS had higher admission and fasting glucose and also HbA1c levels than those with others.

Association of Common Variants of CDKN2A/2B Rs10811661 (C/T)and WFS1 Rs6446482 (C/G) to Type 2 Diabetes Mellitus in the Indian Population of Eastern Uttar Pradesh

Aim: Recent genome-wide association studies (GWAS) have identified several unsuspected genes that significantly increase the risk of type 2 diabetes mellitus (T2DM). We aimed to replicate the association of a common variant each in CDKN2A/2B (rs10811661) and WFS1 (rs6446482) in the population of Eastern Uttar Pradesh, India. These variants have been identified to be differentially associated with T2DM in different ethnic groups in previous GWAS. Results: We found SNP rs10811661 of CDKN2A/2B (OR 1.50, 95% CI 1.109-2.032, P=0.009) and SNP rs6446482 of WFS1 (OR 1.43, 95% CI 1.074-1.896, P=0.014) as significant risk factors for T2DM in Eastern Uttar Pradesh population. Normal Glucose-Tolerant (NGT) subjects carrying risk allele of rs10811661 (C/T) and rs6446482 (C/G) polymorphisms had significantly higher Fasting Plasma Glucose (FPG) and 2-hour Postprandial Plasma Glucose (2h-PPPG) levels compared to non-carriers. Conclusion: Our study replicates the association of well established common variants of CDKN2A/2B rs10811661 (C/T) and WFS1 rs6446482 (C/G) with type 2 diabetes in the population of Eastern Uttar Pradesh, India. Interestingly, our data show larger effect size for both of the SNPs than those reported in European populations.

Dilemma in Diabetes Care Relates to Its Complications: Strategies for Prevention

The dilemma concerning the prevailing classification of Type 1 and Type 2 diabetes is a serious hindrance to effective diabetes care. Many patients who are classified with Type 2 diabetes have symptoms and require treatment similar to those classified with Type 1 diabetes. In addition, patients are often diagnosed with diabetes as a result of elevated fasting blood glucose instead of 2-hour postprandial glucose levels or oral glucose tolerance tests. The misdiagnosis of diabetes accompanied by prescription of oral hypoglycemic agents or antihypertensive therapy, have caused unwarranted health problems in people who may not have diabetes. In this article, patients are presented who illustrate the misdiagnosis of diabetes and the need of proper testing to uncover diabetes. Additional case histories indicate the effect that oral hypoglycemic agents and antihypertensive medications may have on patient health. Suggestions are made regarding proper diagnosis and care. In patients with established diabetes, adequate control of glycemia with insulin, diet restriction and weight reduction, fundamental to prevention of microvascular and macrovascular complications, is stressed. Hospitalizations are preventable if professionals spend time explaining details of diabetic care to patients thereby enabling them to take full responsibility of their illness. Glucose control with insulin therapy, concomitantly with means for weight reduction in obese individuals, must be discussed in a repetitive fashion with the patient. Uncontrolled diabetes, resulting in frequent hospitalizations for a variety of complications, has markedly escalated the cost of diabetic care. Patient education and cooperation are the cornerstone of successful diabetes therapy and the mainstay of prevention of diabetes complications. Thereby, the cost of diabetes care will be reduced. The classification of Type 1 and Type 2 diabetes conveys little to the patients about diabetes which is a potentially devastating disease, nevertheless, with full attention to glucose control, healthy living is attainable. Utmost care should be taken to identify if the person does or does not have diabetes by appropriate testing and attention to proper therapy.

Effects of fasting and/or postprandial glucose on heart rate recovery in patients with coronary heart disease

The impact of both fasting and postprandial glycaemia on heart rate recovery (HRR) has not been studied in patients with coronary heart disease (CHD). For this reason, we sought to determine the relationships between HRR and both fasting and postprandial glycaemia. A total of 4079 patients with baseline fasting plasma glucose (FPG) levels and 706 patients with 2-hour postprandial glucose (2hPG) levels were identified from the Coronary Artery Surgery Study registry, a database of 24,958 patients with suspected or proven CHD who had undergone cardiac catheterization between 1974 and 1979. Median long-term follow-up was 14.7 years (interquartile range: 9.8-16.2 years). The relationships between HRR and both FPG and 2hPG were studied. In univariate analyses, increasing levels of both FPG and 2hPG were significantly associated with lower HRR. In multivariate models adjusted for age, exercise tolerance in METs, resting heart rate and maximum systolic blood pressure during exercise testing, FPG remained significantly associated with HRR while 2hPG did not. Both raised FPG and decreased HRR are independent predictors of total and cardiovascular (CV) mortality in subjects with CHD. Our data suggest that the mortality risk associated with elevated FPG may in part be due to deleterious effects on autonomic regulation of CV function, as reflected by lower HRR. Further studies are required to determine whether or not non-pharmacological and/or pharmacological treatments of increased fasting glucose have a beneficial influence on HRR.

Glycemic Characteristics and Neonatal Outcomes of Women Treated for Mild Gestational Diabetes

To estimate the association between fasting and 2-hour postprandial blood glucose levels and neonatal outcomes in women treated for mild gestational diabetes. In this secondary analysis of a multicenter randomized treatment trial of mild gestational diabetes, the median fasting and 2-hour postprandial glucose levels were analyzed in 2-week intervals and change over time (slope) was calculated for women with gestational diabetes (abnormal oral glucose tolerance test) and a fasting glucose less than 95 mg/dL who received nutritional management with self blood glucose monitoring and insulin as needed. Regression analyses were performed to estimate the relationship between median fasting and postprandial glucose and neonatal fat mass, cord blood C-peptide, birth weight, large-for-gestational-age neonates, macrosomia (greater than 4,000 g), and neonatal hypoglycemia. Among 460 women with gestational diabetes, median fasting (P<.001), postprandial breakfast (P<.001), and postprandial lunch (P<.001) glucose values declined over the treatment period, whereas postprandial dinner values remained stable (P=.83). Higher median fasting glucose during the first 2 weeks of treatment was significantly associated with increased odds ratios for neonatal fat mass (1.35; 95% CI 1.09-1.66; P=.006) and elevated C-peptide (1.29; CI 1.09-1.52; P=.003). Higher median fasting glucose during the last 2 weeks before delivery was associated with higher rates of large-for-gestational-age neonates (1.27; CI 1.05-1.53; P=.01), macrosomia (1.32; CI 1.04-1.65; P = .02), and elevated C-peptide (1.19; CI 1.03-1.38; P=.02). In women treated for mild gestational diabetes, higher fasting glucose during initiation of diet therapy was associated with increased neonatal fat mass and elevated C-peptide and during the last 2 weeks before delivery with macrosomia, large-for-gestational age, and elevated C-peptide. II.

Letter: Predictive Clinical Parameters for the Therapeutic Efficacy of Sitagliptin in Korean Type 2 Diabetes Mellitus (Diabetes Metab J 2011;35:159-65)

Type 2 diabetes mellitus (T2DM) is a complex progressive metabolic derangement associated with comorbidities such as obesity, dyslipidemia, and hypertension. Although a wide range of pharmacotherapies is available for T2DM, determining management strategies for T2DM that balance effectiveness, safety, and tolerability remains complex and challenging. The prevalence of T2DM has increased rapidly in Asia, including South Korea, over the past several decades [1]. The pathophysiologic mechanisms underlying T2DM in Asia are thought to be different from those in Western countries. In particular, pancreatic β-cell dysfunction may be important for the development of T2DM in certain Asian populations [2,3]. Progressive β-cell failure, weight gain and hypoglycemia are the main side effects of sulfonylurea, one of the most commonly used antidiabetic agents. Long-term use of sulfonylurea can lead to the failure of monotherapy and ultimate dependence on insulin injections. Glucagon like peptide (GLP)-1 stimulates pancreatic β-cell differentiation and proliferation, and inhibits apoptosis [4]. Dipeptidyl peptide-4 (DPP-4) inhibitors enhance levels of active incretin hormones, gut-derived peptides that are released into the circulation after eating [5]. Sitagliptin is an oral, once-daily, potential, highly selective DPP-4 inhibitor. Numerous clinical studies of sitagliptin have been reported since the US Food and Drug Administration approved sitagliptin for monotherapy or combination therapy with metformin or thiazolidinedione in 2006 [5-9]. According to a systemic review and meta-analysis, DPP-4 inhibitors lowered HbA1C by 0.74% (95% confidence interval [CI], 0.62% to 0.85%) compared with placebo [10]. Most studies indicate that sitagliptin treatment leads to significant improvements in β-cell function. Given the important role that β-cell dysfunction plays in the progression of hyperglycemia, especially in Asian patients, sitagliptin treatment may be of particular therapeutic relevance for T2DM in Asian contexts. However, clinical studies of sitagliptin therapies in Asian or Korean diabetic patients are rare. A 2009 study found that 18 week sitagliptin monotherapy was associated with significantly improved glycemic control (mean HbA1c reduction, -1.0%) and was well tolerated by T2DM patients from China, India, and Korea [11]. According to this study, the reduction of HbA1C relative to placebo was greater in Korean and Indian patients than in Chinese patients. The mean (95% CI) reductions in HbA1C with sitagliptin treatment were -1.4% (-1.9% to -0.8%) in Korean patients, -1.4% (-1.7% to -1.0%) in Indian patients, and -0.7% (-0.9% to -0.5%) in Chinese patients. Furthermore, Korean patients showed the greatest reductions of fasting glucose and 2-hour postprandial glucose levels. However, the reasons for these differences were not elucidated, although the authors suggested regional differences in environment, genetics, or adherence to study co-interventions such as diet and exercise. Due to the current insufficiency of Asian or Korean data regarding sitagliptin efficacy in patients with T2DM, the study by Kim et al. [12] is particularly relevant. In that study, younger, thinner diabetic patients were observed to have better therapeutic results than older, heavier patients, suggesting that BMI and age should be considered before the selection of sitagliptin or other DPP-4 inhibitors for use in diabetic therapies. Treatment response was defined as >10% HbA1c reduction or >20% fasting glucose reduction, and by this definition, the frequency of response in their sample was 81%. As many previous clinical studies defined successful glucose-lowering effects according to the number of patients with HbA1c <7%, additional studies are necessary to assess the therapeutic effects of sitagliptin and to identify clinical characteristics of patients that predict sitagliptin response.

Determining the Factors that Influence the Insulin Requirements in Type 2 Diabetic Patients

Background: The initial insulin dose is often determined by clinical experience or with a formula using the body weight. However, it may be difficult to determine the initial insulin dose because various factors such as insulin sensitivity and the glycemic status can influence the insulin requirement. The purpose of this study was to assess the factors that influence the initial insulin requirement in insulin naive patients with type 2 diabetes mellitus. Methods: A total 128 patients who were admitted for glycemic control were investigated. The patients were managed with longacting insulin glargine and rapid-acting insulin lispro. Results: The basal insulin requirement was positively correlated with waist circumference, body mass index (BMI), the HbA1C, AST, ALT, fasting plasma glucose and 2-hour postprandial glucose levels and the homeostasis model assessment of insulin resistance (HOMA-IR), but it was negatively correlated with age and the stimulated C-peptide level. The daily insulin requirement was positively correlated with waist circumference, BMI, the HbA1C, AST, ALT, triglyceride, fasting plasma glucose and 2-hour postprandial glucose level and HOMA-IR, but it was negatively correlated with age. On the multiple linear regression analysis, the basal insulin requirement was independently associated with BMI (β = 0.507, P < 0.001), the 2-hour postprandial glucose level (β = 0.307, P < 0.001), the ALT level (β = 0.214, P = 0.015) and the meal-stimulated C-peptide level (β = -0.209, P = 0.010). The daily insulin require ment was independently associated with BMI (β = 0.508, P < 0.001) and the 2-hour postprandial glucose level (β = 0.404, P < 0.001). Conclusion: Our results show that the BMI and 2-hour postprandial glucose level are useful predictors of the initial insulin requirement in insulin naive type 2 diabetic patients. It may be prudent to consider the other various factors that influence the insulin re quirement together when insulin therapy is required. (Endocrinol Metab 25:110-118, 2010)

Is Monitoring of 2-hour Postprandial Glucose Level Suitable for Type 2 Diabetic Patients?

Is Monitoring of 2-hour Postprandial Glucose Level Suitable for Type 2 Diabetic Patients?

Effects of Long‐term 4‐Aminopyridine Therapy on Glucose Tolerance and Glucokinetics in Patients with Spinal Cord Injury

To assess the effects of the potassium channel blocker, 4-aminopyridine, on glucose tolerance and glucokinetics in patients with spinal cord injury. Prospective, dose level-blinded study. University-affiliated, tertiary-level care, Veterans Affairs medical center, and a university-affiliated research center. Thirty-one patients with spinal cord injury of more than 1 year's duration. In a fasting state, patients ingested 75 g of glucose and completed a 5-hour oral glucose tolerance test before and after 6 months of treatment with an oral, immediate-release formulation of 4-aminopyridine. The time course of glucose plasma concentrations during the oral glucose tolerance tests was profiled for each patient, and glucokinetic parameters were estimated. Results were compared at baseline and after 6 months of treatment with 4-aminopyridine. Of the 31 patients, 29 (94%) had impaired glucose tolerance at baseline. After 6 months of treatment with 4-aminopyridine, 12 (41%) of the 29 patients had a 2-hour postprandial glucose level that no longer supported a diagnosis of impaired glucose tolerance. No significant changes or clinically important trends were seen in fasting blood glucose concentrations or in other glucokinetic parameters in these patients. The long-term administration of an oral, immediate-release formulation of 4-aminopyridine to patients with longstanding spinal cord injury was associated with readily discernible, potentially clinically significant improvements in glucose tolerance. Because impaired glucose tolerance is a common finding in patients with spinal cord injury, more research, including randomized controlled trials with large study populations, is warranted on this potential treatment.

Avaliação do risco cardiovascular segundo os critérios de Framingham em pacientes com diabetes tipo 2

The aim of our study was to evaluate cardiovascular risk (CR) in type 2 diabetic (T2DM) patients according to Framingham criteria and its possible relationship with other risk factors not included in the Framingham score. We evaluated 333 T2DM outpatients (215 females), aged 56.9+/-9.7 years followed regularly from March 2004 to February 2005 in the Diabetes Unit in our University Hospital. The known diabetes duration was 12 (0-43) years. In order to determinate the risk of death from coronary artery disease (CAD), we applied the Framingham score. Patients were classified in two groups, according to their probability of having a cardiovascular event in ten years: <or=20% and>20%. We intended to establish a correlation between the CR verified in this population and other variables probably related to CR not included on Framingham score. The CR in ten years was 18.7+/-10.8% in the whole population, being higher in male than female [20% (2-53) vs. 15% (1-27); p<0.001]. Fifty five percent of males and 38.6% of females had a CR>20% according to Framingham score (p=0.003). The CR was related to diabetes duration, triglycerides (TG), creatinine and 2-hour postprandial plasma glucose (2G) levels and abdominal circumference (AC) either according to International Diabetes Federation (p<0.001) or World Health Organization (p=0.003) criteria. In the stepwise multivariate analyses we found an independent and significant correlation of CR with the following variables: gender (male), diabetes duration, plasma creatinine levels, AC and TG (p<0.001). Our T2DM patients represent a high-risk population for cardiovascular events according to the Framingham score, mainly males. Routine use of Framingham score, which is feasible and noninvasive, could identify such patients and institute precocious and intensive measures in order to reduce their cardiovascular risk.

Diurnal glycemic profile in obese and normal weight nondiabetic pregnant women

A paucity of data exists concerning the normal glycemic profile in nondiabetic pregnancies. Using a novel approach that provides continuous measurement of blood glucose, we sought to evaluate the ambulatory daily glycemic profile in the second half of pregnancy in nondiabetic women. Fifty-seven obese and normal weight nondiabetic subjects were evaluated for 72 consecutive hours with continuous glucose monitoring by measurement interstitial glucose levels in subcutaneous tissue every 5 minutes. Subjects were instructed not to modify their lifestyle or to follow any dietary restriction. For each woman, mean and fasting blood glucose values were determined; for each meal during the study period, the first 180 minutes were analyzed. For the study group, the fasting blood glucose level was 75 +/- 12 mg/dL; the mean blood glucose level was 83.7 +/- 18 mg/dL; the postprandial peak glucose value level was 110 +/- 16 mg/dL, and the time interval that was needed to reach peak postprandial glucose level was 70 +/- 13 minutes. A similar postprandial glycemic profile was obtained for breakfast, lunch, and dinner. Obese women were characterized by a significantly higher postprandial glucose peak value, increased 1- and 2-hour postprandial glucose levels, increased time interval for glucose peak, and significantly lower mean blood glucose during the night. No difference was found in fasting and mean blood glucose between obese and nonobese subjects. Glycemic profile characterization in both obese and normal weight nondiabetic subjects provide a measure for the desired level of glycemic control in pregnancy that is complicated with diabetes mellitus.

Fasting or two-hour postprandial plasma glucose levels in early months of pregnancy as screening tools for gestational diabetes mellitus developing in later months of pregnancy.

The present study was done to find out whether the fasting or 2-hour postprandial plasma glucose (PPPG) levels in early months of pregnancy can be used as screening tools for gestational diabetes mellitus (GDM) developing in later months of pregnancy. Fasting and 2-hour PPPG levels were measured in the early months of pregnancy in 246 women attending the antenatal clinic of the author. All of the women underwent glucose challenge tests with 50 grams of glucose at 24-28 weeks and if the value exceeded 140 mg%, a three-hour oral glucose tolerance test (OGTT) with 100 grams of glucose was performed to diagnose GDM. The present study found that the incidence of GDM was 10.5% in the third trimester. Statistical analysis did not show any correlation between fasting and the PPPG values in the early months and GDM in later months of pregnancy. Fasting or PPPG values cannot be used as efficient screening tools for GDM developing in the later months of pregnancy.

Antidiabetic effect of novel modulating peptides of G-protein-coupled kinase in experimental models of diabetes.

G-protein-coupled receptor kinases (GRKs) play a key role in agonist-induced desensitisation of G-protein-coupled receptors (GPCRs) that are involved in metabolic regulation and glucose homeostasis. Our aim was to examine whether small peptides derived from the catalytic domain of GRK2 and -3 would ameliorate Type 2 diabetes in three separate animal models of diabetes. Synthetic peptides derived from a kinase-substrate interaction site in GRK2/3 were initially screened for their effect on in vitro melanogenesis, a GRK-mediated process. The most effective peptides were administered intraperitoneally, utilising a variety of dosing regimens, to Psammomys obesus gerbils, Zucker diabetic fatty (ZDF) rats, or db/db mice. The metabolic effects of these peptides were assessed by measuring fasting and fed blood glucose levels and glucose tolerance. Two peptides, KRX-683(107) and KRX-683(124), significantly reduced fed-state blood glucose levels in the diabetic Psammomys obesus. In animals treated with KRX-683(124) at a dose of 12.5 mg/kg weekly for 7 weeks, ten of eleven treated animals responded with mean blood glucose significantly lower than controls (4.7+/-0.4 vs 16.8+/-0.8 mmol/l, p</=0.0001). Significant reductions in blood glucose compared with controls were also seen in ZDF rats administered KRX-683(124) and in db/db mice, which had significantly reduced fasting and 2-hour postprandial glucose levels after the treatment. Sequence-based peptides derived from GRK2/3 have an antidiabetic effect demonstrated in three different animal models of Type 2 diabetes. By modulating GRK2/3 activity, these peptides enhance GPCR-initiated signal transduction, resulting in improved glucose homeostasis. Sequence-based peptide modulation of GRK could prove useful in the treatment of Type 2 diabetes.

Clinical significance, pathogenesis, and management of postprandial hyperglycemia.

It is well established that strict glycemic control (hemoglobin A1c <7.0%) can prevent the microvascular complications of diabetes mellitus. Recent studies indicate that elevated plasma glucose concentrations are an independent and clinically significant risk factor for cardiovascular disease in nondiabetic and diabetic individuals. Thus, isolated postprandial hyperglycemia (2-hour postprandial glucose level >140 mg/dL [>7.8 mmol/L]) in the face of normal fasting plasma glucose (<110 mg/dL [<6.1 mmol/L]) and normal hemoglobin A1c (<6.1%) values is associated with a 2-fold increased risk of death from cardiovascular disease. These observations imply that more strict glycemic control is required to prevent macrovascular disease than microvascular disease. This review summarizes epidemiologic and experimental studies linking postprandial hyperglycemia to cardiovascular disease and therapeutic approaches available and in development to treat this disorder.

Using glucose tolerance test results to predict insulin requirement in women with gestational diabetes.

This study was done to test the clinical impression that the result of the oral glucose tolerance test could be used to predict which patients with gestational diabetes did not need insulin therapy. If this was true, a full blood sugar profile assessment could be avoided in many of these women. The second analysis was to test the clinical impression that the fasting glucose level was the best predictor of insulin requirement in women with gestational diabetes. The results of the study showed that none of the 3 readings of the oral glucose tolerance test could be used to predict reliably which patients did not need insulin therapy. Hence, blood sugar profile assessment of all patients with gestational diabetes is still necessary. The receiver-operator characteristic curves also showed that the 2-hour postload glucose level during the 75 g load glucose tolerance test was a better predictor of insulin requirement than the fasting glucose level.

Persistence of Low HDL-C Levels After Weight Reduction in Older Men With Small LDL Particles

LDL subclass pattern B is characterized by a predominance of small LDL particles (LDL peak particle size < or = 255 A) and is associated with increased plasma triglyceride (TG) and reduced HDL cholesterol (HDL-C) concentrations. This study compared the effect of weight loss on lipoprotein and glucose metabolism in 15 healthy, obese (body mass index [BMI], 30.9 +/- 2.4 kg/m2), older (60 +/- 9 years) men with LDL pattern B and in 25 men of comparable age and BMI with LDL pattern A (LDL peak particle size > or = 260 A). At baseline, men with LDL pattern B had higher TG and lower apolipoprotein (apo) A-I, HDL-C, and HDL2-C levels (P < .001) than men with LDL pattern A, while the total cholesterol and LDL cholesterol levels and fasting and 2-hour postprandial glucose and insulin levels did not differ between groups. With weight loss (10.1 +/- 3.6 kg) there were significant decreases in 2-hour postprandial glucose and insulin levels in men with LDL patterns B and A (P < .05). However, the change in plasma TG, HDL-C, HDL2-C, and apoA-I levels with weight loss differed between groups. In men with LDL pattern A, plasma TG levels decreased by 15% (P < .001) compared with a 34% (P < .001) decrease in LDL pattern B (two-factor ANOVA, P < .01). Plasma HDL-C concentrations increased by 0.16 mmol/L (P < .001) in the men with LDL pattern A but by only 0.07 mmol/L in the men with LDL pattern B (two-factor ANOVA, P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Growth after recombinant human growth hormone treatment in children with chronic renal failure: Report of a multicenter randomized double-blind placebo-controlled study

Objective: To determine whether treatment with recombinant human growth hormone (rhGH) enhances growth rate in growth-retarded children with chronic renal failure. Design: One hundred twenty-five prepubertal growth-retarded children with chronic renal failure were randomly assigned to receive either rhGH (n = 82) or placebo (n = 43) for 2 years. Setting: The study was undertaken at 17 pediatric nephrology centers in the United States. Measurements: Growth rate, standardized height, bone age, fasting and 2-hour postprandial glucose and insulin levels, biochemical values, and insulin-like growth factor I and anti-growth hormone antibody levels were evaluated serially during the 2-year study period. Results: Standardized height increased from −2.94 to −1.55 in the rhGH group after 24 months of treatment, and decreased from −2.82 to −2.91 in the placebo group ( p <0.00005). Patients in the rhGH group who completed 24 months of study (n = 55) had a greater growth rate during the first year (10.7 ± 3.1 cm/yr) than during the second year (7.8 ± 2.1 cm/yr) of treatment. These growth rates were significantly greater than those in the placebo group (n = 27) in the first (6.5 ± 2.6 cm/yr) and second (5.5 ± 1.9 cm/yr) years ( p <0.00005 for both years). The mean Δ height age minus the Δ bone age was positive in the rhGH group, suggesting improved final height potential. There was no significant difference in the change in calculated creatinine clearance over baseline values in the rhGH group from that in the placebo group after 24 months of study ( p = 0.63). Mean fasting and postprandial insulin values were elevated at 12 months but not at 24 months in the rhGH-treated patients. Mean fasting and 2-hour postprandial glucose values at 24 months were not significantly elevated over baseline values in either group. Conclusions: Growth rate and standardized height were significantly increased in growth-retarded prepubertal children with chronic renal failure when rhGH was used. The acceleration in growth was not associated with undue advancement of bone age. No clinically significant side effects were associated with rhGH treatment. The use of rhGH in growth-retarded children with chronic renal failure may facilitate the achievement of the inherent growth potential of such children. (J P ediatr 1994;124:374-82)