High Incidence of Impaired Glucose Regulation in Patients With no Known History of Diabetes Mellitus But With Hyperglycemia After Undergoing a Cardiac Surgical Procedure

ObjectiveTo determine the implications of the presence of hyperglycemia after a cardiac surgical procedure in patients with no history of diabetes mellitus (DM).MethodsWe conducted a prospective study of 50 consecutive patients with no known history of DM who underwent a cardiac surgical procedure and had postoperative hyperglycemia (plasma glucose levels ≥ 110 mg/dL), requiring an insulin drip to achieve tight glucose control. These patients underwent a 2-hour oral glucose tolerance test (OGTT) at 6 weeks postoperatively to determine the percentage of subjects with impaired fasting glucose (IFG), impaired glucose tolerance (IGT), or type 2 DM.ResultsOf the 50 patients, 32 (64%) were found to have persistent glucose dysregulation. On the basis of OGTT results, 20% had IFG, 16% had both IFG and IGT, 10% had only IGT, and 18% had type 2 DM. Of the patients with newly diagnosed diabetes, 89% had a 6-week postoperative fasting plasma glucose (FPG) concentration of < 126 mg/dL. There was a significant correlation between the preoperative FPG levels and the 6-week postoperative 2-hour OGTT glucose levels (P < .01). No correlation was found between the 6-week postoperative FPG levels and the 2-hour OGTT glucose levels (P = .26).ConclusionHyperglycemia after a cardiac surgical procedure implies a high risk of persistent glucose dysregulation. Preoperative FPG levels correlated better with 2-hour OGTT results than did the 6-week postoperative FPG values, but both were insensitive markers for diagnosing type 2 DM in these patients. In our cohort, hemoglobin A1c was not predictive of abnormalities of glucose metabolism. Our data support the need for performing a postoperative OGTT in patients with no known history of DM but the presence of hyperglycemia after a cardiac operation. (Endocr Pract. 2009;15:425-430)     

Fasting Plasma Glucose (FPG) and the Risk of Impaired Glucose Tolerance in Obese Children and Adolescents

A timely diagnosis of impaired glucose tolerance (IGT) is desirable in obesity. The oral glucose tolerance test (OGTT), the gold standard to diagnose this condition, may not be realistically performed in all patients due to discomfort, labor, and cost. The aim of this study was to assess whether one or more biochemical indexes measured in fasting conditions could be used to identify obese children at risk of IGT. A cohort of 563 white obese children and adolescents (M/F: 315/248; aged 4–17 years) was recruited and underwent anthropometric evaluation and OGTT. Anthropometric parameters, fasting plasma glucose (FPG), fasting serum insulin (FSI), and homeostasis model assessment of insulin resistance (HOMA_IR) were tested in pursuit of a possible threshold to be used as a predictor of IGT. Thirty‐seven children (6.9%) had IGT and one child (0.1%) had type 2 diabetes (T2D). FPG, FSI, and HOMA_IR were all significantly higher in children with IGT than in children without IGT. Receiver‐operating characteristic (ROC) curve analyses run for gender and puberty‐adjusted FPG, FSI, and HOMA_IR were all significant: area under the curve (95% confidence interval) equaled 0.68 (0.59–0.76), 0.66 (0.56–0.76), and 0.68 (0.59–0.78), respectively. The three parameters did not show significantly different sensitivity/specificity in the pooled population or in the gender/puberty subgroups. Thresholds varied among gender/puberty subgroups for FSI and HOMA_IR, but not for FPG, which showed a fixed threshold of 86 mg/dl. A gender/puberty independent cutoff of FPG may be considered a screening tool to narrow clinical indication to OGTT in obese white children and adolescents.     

Influence of Lower Cutoff Values for 100-G Oral Glucose Tolerance Test and Glycemic Profile for Identification of Pregnant Women at Excessive Fetal Growth Risk

ObjectiveTo evaluate data from patients with normal oral glucose tolerance test (OGTT) results and a normal or impaired glycemic profile (GP) to determine whether lower cutoff values for the OGTT and GP (alone or combined) could identify pregnant women at risk for excessive fetal growth.MethodsWe classified 701 pregnant women with positive screening for gestational diabetes mellitus (GDM) into 2 categories-(i) normal 100-g OGTT and normal GP and (2) normal 100-g OGTT and impaired GP—to evaluate the influence of lower cutoff points in a 100-g OGTT and GP (alone or in combination) for identification of pregnant women at excessive fetal growth risk. The OGTT is considered impaired if 2 or more values are above the normal range, and the GP is impaired if the fasting glucose level or at least 1 postprandial glucose value is above the normal range. To establish the criteria for the OGTT (for fasting and 1,2, and 3 hours after an oral glucose load, respectively), we considered the mean (75 mg/dL, 120 mg/dL, 113 mg/dL, and 97 mg/dL), mean plus 1 SD (85 mg/dL, 151 mg/dL, 133 mg/dL, and 118 mg/dL), and mean plus 2 SD (95 mg/dL, 182 mg/dL, 153 mg/dL, and 139 mg/dL); and for the GP, we considered the mean and mean plus 1 SD (78 mg/dL and 92 mg/dL for fasting glucose levels and 90 mg/dL and 130 mg/dL for 1- or 2- hour postprandial glucose levels, respectively).ResultsSubsequently, the women were reclassified according to the new cutoff points for both tests (OGTT and GP). Consideration of values, in isolation or combination, yielded 6 new diagnostic criteria. Excessive fetal growth was the response variable for analysis of the new cutoff points. Odds ratios and their respective confidence intervals were estimated, as were the sensitivity and specificity related to diagnosis of excessive fetal growth for each criterion. The new cutoff points for the tests, when used independently rather than collectively, did not help to predict excessive fetal growth in the presence of mild hyperglycemia.ConclusionDecreasing the cutoff point for the 100g OGTT (for fasting and 1, 2, and 3 hours) to the mean (75 mg/dL, 120 mg/dL, 113 mg/dL, and 97 mg/dL) in association with the GP (mean or mean plus 1 SD—78 mg/dL and 92 mg/dL for the fasting state and 90 mg/dL and 130 mg/dL for 1- or 2-hour postprandial values—increased the sensitivity and specificity, and both criteria had statistically significant predictive power for detection of excessive fetal growth. (Endocr Pract. 2008;14:678-685)     

A Cross-Sectional Study of the Association between the 1-Hour Oral Glucose Tolerance Test and the Metabolic Syndrome in a High-Risk Sample with Impaired Fasting Glucose

Objective: The aim of this study was to evaluate the association between the 1-hour oral glucose tolerance test (OGTT) (≥155 mg/dL) and metabolic syndrome (MS) in a sample with previous impaired fasting glucose (IFG).Methods: Three hundred and twenty four Peruvian subjects with a history of IFG ≥100 mg/dL were selected for a cross-sectional study. They underwent a 75 g OGTT and were assigned to different groups according to the result. We evaluated the association between 1-hour OGTT and MS.Results: The mean age was 56.5 ± 12.6 years and 191 (61.5%) were female. During the OGTT, we found 28 (8.6%) subjects with diabetes, 74 (22.8%) with IGT, and 222 (68.5%) with a normal glucose tolerance test with a 2-hour glucose <140 mg/dL (NGT). In the NGT group, 124 (38.3%) had 1-hour glucose levels <155 mg/dL, while 98 (30.2%) had 1-hour glucose levels ≥155 mg/dL. Evaluating the association between the 1-hour value in the OGTT and MS, we found that subjects with a 1-hour glucose ≥155 mg/dL were more than twice as likely to have MS as those with a 1-hour glucose <155 mg/dL (odds ratio = 2.64, 95% confidence interval: 1.52 to 4.57). In addition, body mass index, fasting glycemia, triglycerides, and waist circumferences were significantly higher in subjects with 1-hour glucose levels ≥155 mg/dL compared to those with 1-hour glucose levels <155 mg/dL (P<.05).Conclusion: Among subjects with IFG, performing an OGTT was helpful to identify subjects with 1-hour glucose levels ≥155 mg/dL and NGT who were significantly more likely to have MS and a worse cardiometabolic risk profile.Abbreviations: AST = aspartate aminotransferase; BMI = body mass index; CI = confidence interval; IFG = impaired fasting glucose; IGT = impaired glucose tolerance; LDL = low-density lipoprotein; MS = metabolic syndrome; NGT = normal glucose tolerance; OGTT = oral glucose tolerance test; OR = odds ratio; T2DM = type 2 diabetes; TG = triglycerides     

Lack of Correlation Between 1,5-Anhydroglucitol Assay and Oral Glucose Tolerance Test in Patients with Cystic Fibrosis

ObjectiveTo determine whether the 1,5-anhydroglucitol (1,5-AG) assay, which reflects serum glucose levels during the preceding 2 weeks, could be used as an alternative to the current standard screening test for cystic fibrosis-related diabetes (CFRD)—the oral glucose tolerance test (OGTT).MethodsSerum 1,5-AG, hemoglobin A1c (A1C), fructosamine, and glucose at various time intervals during the OGTT were measured in 10 patients, 19 to 36 years old, with cystic fibrosis. Correlation coefficients were calculated to compare 1,5-AG with A1C, fructosamine, and serum glucose levels during the OGTT, and the mean 1,5- AG, A1C, and fructosamine for normal glucose tolerance, impaired glucose tolerance (IGT), and CFRD were compared statistically.ResultsOn the basis of the 120-minute OGTT, 1 of the 10 study subjects had CFRD and 4 had IGT. The mean 1,5-AG for patients with normal glucose tolerance was not significantly different from that for patients with IGT (P = .063). The 1,5-AG value was not significantly correlated with serum glucose during the OGTT, A1C, or fructosamine.ConclusionIn this pilot study, we found no significant correlation between 1,5-AG and glucose values during the OGTT or between 1,5-AG and other glycemic markers.Hence, the utility of the 1,5-AG assay for screening for CFRD in the population of patients with cystic fibrosis may be limited. (Endocr Pract. 2010;16:167-170)     

Skin Autofluorescence Based Decision Tree in Detection of Impaired Glucose Tolerance and Diabetes

Aim

Diabetes (DM) and impaired glucose tolerance (IGT) detection are conventionally based on glycemic criteria. Skin autofluorescence (SAF) is a noninvasive proxy of tissue accumulation of advanced glycation endproducts (AGE) which are considered to be a carrier of glycometabolic memory. We compared SAF and a SAF-based decision tree (SAF-DM) with fasting plasma glucose (FPG) and HbA1c, and additionally with the Finnish Diabetes Risk Score (FINDRISC) questionnaire±FPG for detection of oral glucose tolerance test (OGTT)- or HbA1c-defined IGT and diabetes in intermediate risk persons.

Methods

Participants had ≥1 metabolic syndrome criteria. They underwent an OGTT, HbA1c, SAF and FINDRISC, in adition to SAF-DM which includes SAF, age, BMI, and conditional questions on DM family history, antihypertensives, renal or cardiovascular disease events (CVE).

Results

218 persons, age 56 yr, 128M/90F, 97 with previous CVE, participated. With OGTT 28 had DM, 46 IGT, 41 impaired fasting glucose, 103 normal glucose tolerance. SAF alone revealed 23 false positives (FP), 34 false negatives (FN) (sensitivity (S) 68%; specificity (SP) 86%). With SAF-DM, FP were reduced to 18, FN to 16 (5 with DM) (S 82%; SP 89%). HbA1c scored 48 FP, 18 FN (S 80%; SP 75%). Using HbA1c-defined DM-IGT/suspicion ≥6%/42 mmol/mol, SAF-DM scored 33 FP, 24 FN (4 DM) (S76%; SP72%), FPG 29 FP, 41 FN (S71%; SP80%). FINDRISC≥10 points as detection of HbA1c-based diabetes/suspicion scored 79 FP, 23 FN (S 69%; SP 45%).

Conclusion

SAF-DM is superior to FPG and non-inferior to HbA1c to detect diabetes/IGT in intermediate-risk persons. SAF-DM’s value for diabetes/IGT screening is further supported by its established performance in predicting diabetic complications.     

Extremely short duration high intensity interval training substantially improves insulin action in young healthy males

Background

Impaired glucose tolerance (IGT) is a prediabetic state. If IGT can be prevented from progressing to overt diabetes, hyperglycemia-related complications can be avoided. The purpose of the present study was to examine whether pioglitazone (ACTOS^®) can prevent progression of IGT to type 2 diabetes mellitus (T2DM) in a prospective randomized, double blind, placebo controlled trial.

Methods/Design

602 IGT subjects were identified with OGTT (2-hour plasma glucose = 140–199 mg/dl). In addition, IGT subjects were required to have FPG = 95–125 mg/dl and at least one other high risk characteristic. Prior to randomization all subjects had measurement of ankle-arm blood pressure, systolic/diastolic blood pressure, HbA_1C, lipid profile and a subset had frequently sampled intravenous glucose tolerance test (FSIVGTT), DEXA, and ultrasound determination of carotid intima-media thickness (IMT). Following this, subjects were randomized to receive pioglitazone (45 mg/day) or placebo, and returned every 2–3 months for FPG determination and annually for OGTT. Repeat carotid IMT measurement was performed at 18 months and study end. Recruitment took place over 24 months, and subjects were followed for an additional 24 months. At study end (48 months) or at time of diagnosis of diabetes the OGTT, FSIVGTT, DEXA, carotid IMT, and all other measurements were repeated. Primary endpoint is conversion of IGT to T2DM based upon FPG ≥ 126 or 2-hour PG ≥ 200 mg/dl. Secondary endpoints include whether pioglitazone can: (i) improve glycemic control (ii) enhance insulin sensitivity, (iii) augment beta cell function, (iv) improve risk factors for cardiovascular disease, (v) cause regression/slow progression of carotid IMT, (vi) revert newly diagnosed diabetes to normal glucose tolerance.

Conclusion

ACT NOW is designed to determine if pioglitazone can prevent/delay progression to diabetes in high risk IGT subjects, and to define the mechanisms (improved insulin sensitivity and/or enhanced beta cell function) via which pioglitazone exerts its beneficial effect on glucose metabolism to prevent/delay onset of T2DM.

Trial Registration

clinical trials.gov identifier: NCT00220961     

Impaired Glucose Tolerance or Newly Diagnosed Diabetes Mellitus Diagnosed during Admission Adversely Affects Prognosis after Myocardial Infarction: An Observational Study

Objective

To investigate the prognostic effect of newly diagnosed diabetes mellitus (NDM) and impaired glucose tolerance (IGT) post myocardial infarction (MI).

Research Design and Methods

Retrospective cohort study of 768 patients without preexisting diabetes mellitus post-MI at one centre in Yorkshire between November 2005 and October 2008. Patients were categorised as normal glucose tolerance (NGT n = 337), IGT (n = 279) and NDM (n = 152) on pre- discharge oral glucose tolerance test (OGTT). Primary end-point was the first occurrence of major adverse cardiovascular events (MACE) including cardiovascular death, non-fatal MI, severe heart failure (HF) or non-haemorrhagic stroke. Secondary end-points were all cause mortality and individual components of MACE.

Results

Prevalence of NGT, impaired fasting glucose (IFG), IGT and NDM changed from 90%, 6%, 0% and 4% on fasting plasma glucose (FPG) to 43%, 1%, 36% and 20% respectively after OGTT. 102 deaths from all causes (79 as first events of which 46 were cardiovascular), 95 non fatal MI, 18 HF and 9 non haemorrhagic strokes occurred during 47.2 ± 9.4 months follow up. Event free survival was lower in IGT and NDM groups. IGT (HR 1.54, 95% CI: 1.06–2.24, p = 0.024) and NDM (HR 2.15, 95% CI: 1.42–3.24, p = 0.003) independently predicted MACE free survival. IGT and NDM also independently predicted incidence of MACE. NDM but not IGT increased the risk of secondary end-points.

Conclusion

Presence of IGT and NDM in patients presenting post-MI, identified using OGTT, is associated with increased incidence of MACE and is associated with adverse outcomes despite adequate secondary prevention.     

Continuous glucose monitoring in cystic fibrosis patients according to the glucose tolerance.

Cystic fibrosis (CF) is associated with a long preclinical state of abnormal glucose tolerance. The aim of this study was (i) to evaluate the profile of glucose tolerance in young adults with CF and (ii) to compare these results with those obtained by a continuous subcutaneous glucose monitoring (CGMS). CF subjects with fasting glycemia inferior to 126 mg/dl were included in the study. An oral glucose tolerance test (OGTT) identified the subjects either with a normal glucose tolerance (NGT), or impaired glucose tolerance (IGT), or diabetes. CGMS (Medtronic) was performed during 3 days to analyze mean glucose level, high glucose excursions, and glucose area under the curve (AUC). Forty-nine patients were included in the study. NGT (n=22), IGT (n=17), and diabetes groups (n=10) were comparable except with regard to age and BMI (p<0.001). HbA1c values in diabetes group were significantly higher (p<0.001) than in NGT and IGT groups. CGMS revealed peaks of glucose values superior to 200 mg/dl at least once after a meal in 8 patients (36%) with NGT, in 9 patients (52%) with IGT, and in all patients with diabetes (p<0.01). Mean CGMS glucose and glucose AUC values increased in patients with diabetes compared to patients with NGT and IGT (p<0.05). Peak of CGMS glucose reached 182+/-60 mg/dl in NGT group despite the normal glucose profile at OGTT. In conclusion, CGMS revealed pathological glucose excursions not only in patients with impaired glucose tolerance at OGTT but also in patients with a normal glycemic profile. CGMS could be a useful tool for the early detection of hyperglycemia in patients with CF.     

Serum Uric Acid Is More Strongly Associated with Impaired Fasting Glucose in Women than in Men from a Community-Dwelling Population

Serum uric acid (SUA) levels are associated with metabolic syndrome (MetS) and its components such as glucose intolerance and type 2 diabetes. It is unknown whether there are gender-specific differences regarding the relationship between SUA levels, impaired fasting glucose (IFG) and newly detected diabetes. We recruited 1,209 men aged 60±15 (range, 19–89) years and 1,636 women aged 63±12 (range, 19–89) years during their annual health examination from a single community. We investigated the association between SUA levels and six categories according to fasting plasma glucose (FPG) level {normal fasting glucose (NFG), <100 mg/dL; high NFG-WHO, 100 to 109 mg/dL; IFG-WHO, 110 to 125 mg/dL; IFG-ADA, 100 to 125 mg/dL; newly detected diabetes, ≥126 mg/dL; known diabetes} SUA levels were more strongly associated with the different FPG categories in women compared with men. In women, the associations remained significant for IFG-WHO (OR, 1.23, 95% CI, 1.00–1.50) and newly detected diabetes (OR, 1.33, 95% CI, 1.03–1.72) following multivariate adjustment. However, in men all the associations were not significant. Thus, there was a significant interaction between gender and SUA level for newly detected diabetes (P = 0.005). SUA levels are associated with different categories of impaired fasting glucose in participants from community-dwelling persons, particularly in women.     

Serum Glycated Albumin to Guide the Diagnosis of Diabetes Mellitus

In the diagnosis of diabetes mellitus, hemoglobin A1c (HbA1c) is sometimes measured to determine the need of an oral glucose tolerance test (OGTT). However, HbA1c does not accurately reflect glycemic status in certain conditions. This study was performed to test the possibility that measurement of serum glycated albumin (GA) better assesses the need for OGTT. From 2006 to 2012, 1559 subjects not known to have diabetes or to use anti-diabetic medications were enrolled. Serum GA was measured, and a 75-g OGTT was then performed to diagnose diabetes. Serum GA correlated significantly to age (r = 0.27, p<0.001), serum albumin (r = –0.1179, age-adjusted p = 0.001), body mass index (r = -0.24, age-adjusted p<0.001), waist circumference (r = -0.16, age-adjusted p<0.001), and plasma GA (r = 0.999, p<0.001), but was unaffected by diet (p = 0.8). Using serum GA at 15% for diagnosis of diabetes, the sensitivity, specificity, and area under the receiver-operating characteristic curve were 74%, 85%, and 0.86, respectively. Applying a fasting plasma glucose (FPG) value of < 100 mg/dL to exclude diabetes and of ≥ 126 mg/dL to diagnose diabetes, 14.4% of the study population require an OGTT (OGTT%) with a sensitivity of 78.8% and a specificity of 100%. When serum GA value of 14% and 17% were used to exclude and diagnose diabetes, respectively, the sensitivity improved to 83.3%, with a slightly decrease in specificity (98.2%), but a significant increase in OGTT% (35%). Using combined FPG and serum GA cutoff values (FPG < 100 mg/dL plus serum GA < 15% to exclude diabetes and FPG ≥ 126 mg/dL or serum GA ≥ 17% to diagnose diabetes), the OGTT% was reduced to 22.5% and the sensitivity increased to 85.6% with no change in specificity (98.2%). In the diagnosis of diabetes, serum GA measurements can be used to determine the need of an OGTT.     

The Association between HbA1c,Fasting Glucose, 1-Hour Glucose and 2-Hour Glucose during an Oral Glucose Tolerance Test and Cardiovascular Disease in Individuals with Elevated Risk for Diabetes

Objective

To determine the association between HbA1c, fasting plasma glucose (FPG), 1-hour (1 hPG) and 2-hour (2 hPG) glucose after an oral glucose tolerance test (OGTT) and cardiovascular disease in individuals with elevated risk for diabetes.

Design

We studied the relationship between baseline, updated mean and updated (last) value of HbA1c, FPG, 1 hPG and 2 hPG after an oral 75 g glucose tolerance test (OGTT) and acute CVD events in 504 individuals with impaired glucose tolerance (IGT) at baseline enrolled in the Finnish Diabetes Prevention Study.

Setting

Follow-up of clinical trial.

Participants

504 individuals with IGT were followed with yearly evaluations with OGTT, FPG and HbA1c.

Main Outcome Measure

Relative risk of CVD.

Results

Over a median follow-up of 9.0 years 34 (6.7%) participants had a CVD event, which increased to 52 (10.3%) over a median follow-up of 13.0 years when including events that occurred among participants following a diagnosis of diabetes. Updated mean HbA1c, 1 hPG and 2 hPG, HR per 1 unit SD of 1.57 (95% CI 1.16 to 2.11), p = 0.0032, 1.51 (1.03 to 2.23), p = 0.036 and 1.60 (1.10 to 2.34), p = 0.014, respectively, but not FPG (p = 0.11), were related to CVD. In analyses of the last value prior to the CVD event the same three glycaemic measurements were associated with the CVD events, with HRs per 1 unit SD of 1.45 (1.06 to 1.98), p = 0.020, 1.55 (1.04 to 2.29), p = 0.030 and 2.19 (1.51 to 3.18), p<0.0001, respectively but only 2 hPG remained significant in pairwise comparisons. Including the follow-up period after diabetes onset updated 2 hPG (p = 0.003) but not updated mean HbA1c (p = 0.08) was related to CVD.

Conclusions and Relevance

Current 2 hPG level in people with IGT is associated with increased risk of CVD. This supports its use in screening for prediabetes and monitoring glycaemic levels of people with prediabetes.     

Impact of the Time-Weighted Average Glucose Concentration and Diabetes on In-Hospital Mortality in Critically Ill Patients Older Than 75 Years: A Retrospective Cohort Study

ObjectiveTo evaluate the effects of diabetes and hyperglycemia on in-hospital mortality in critically ill patients older than 75 years.MethodsThis was a single-center retrospective cohort study of patients older than 75 years in the first intensive care unit stay. The patients were divided into the following 4 groups: time-weighted average glucose (TWAG) <140 mg/dL without diabetes (group 1), TWAG ≥140 mg/dL without diabetes (group 2), TWAG <180 mg/dL with diabetes (group 3), and TWAG ≥180 mg/dL with diabetes (group 4). Clinical and laboratory data were analyzed.ResultsA total of 6760 patients over 75 years of age were included, including 2089 patients previously diagnosed with diabetes. The patients in group 2 had the highest in-hospital mortality (27.4%). In the fully adjusted regression model, the risk of in-hospital mortality increased by 76% (odds ratio = 1.76, 95% CI: 1.49-2.08) in group 2 as compared with group 1. Those from groups 3 and 4 exhibited risks equivalent to the risks of those in group 1; similar results were observed in the subgroup analysis. A J-shaped curve relationship and threshold effect were observed in patients without diabetes. For those with diabetes, a flatter curve pattern with a small slope was observed.ConclusionStress hyperglycemia was more detrimental to short-term prognosis than diabetes status in these patients. Looser glucose control may be suitable for patients older than 75 years with diabetes but unnecessary for those without diabetes. Patients with diabetes may be more resistant to the detrimental effects of glucose variations.     

Colesevelam Hydrochloride to Treat Hypercholesterolemia and Improve Glycemia in Prediabetes: A Randomized,Prospective Study

ObjectiveTo assess the effect of the bile acid sequestrant colesevelam hydrochloride in patients with hypercholesterolemia and prediabetes.MethodsIn this 16-week, randomized, double-blind study, adults with untreated prediabetes (2-hour postoral glucose tolerance test [OGTT] glucose ≥ 140 to 199 mg/dL, fasting plasma glucose [FPG] ≥ 110 to 125 mg/ dL, or both), low-density lipoprotein cholesterol (LDL-C) ≥ 100 mg/dL, and triglycerides < 500 mg/dL were randomly assigned to receive colesevelam (3.75 g/d) or placebo. The primary end point was percent change in LDL-C from baseline to week 16 with last observation carried forward. Secondary end points included change in FPG, hemoglobin A1c (A1C), and 2-hour post-OGTT glucose level from baseline to week 16 and attainment of LDL-C and FPG targets.ResultsIn total, 216 patients were randomized (colesevelam, 108; placebo, 108). In comparison with placebo, colesevelam significantly reduced LDL-C (mean treatment difference, -15.6%), non-high-density lipoprotein cholesterol (-9.1%), total cholesterol (-7.2%), apolipoprotein B (-8.1%) (P < .001 for all the foregoing), FPG (median, -2.0 mg/dL; P = .02), and A1C (mean, -0.10%; P = .02). Colesevelam did not significantly change 2-hour post-OGTT glucose (-1.9 mg/dL; P = .75) or high-density lipoprotein cholesterol (-0.5%; P = .80). In addition, colesevelam significantly increased triglyceride levels relative to placebo (median, 14.3%; P < .001). The proportion of patients achieving target levels with colesevelam versus placebo, respectively, was as follows: LDL-C < 100 mg/dL (29% versus 11%; P < .001), A1C < 6.0% (37% versus 25%; P = .05), FPG < 110 mg/dL (48% versus 56%; P = .97), and normalization of glucose (FPG < 100 mg/dL [40% versus 23%; P = .06]). Colesevelam had a weight-neutral effect and was well tolerated.ConclusionColesevelam is an option for managing the lipid profile and normalizing glucose levels in patients with hypercholesterolemia and prediabetes. Further study is warranted to determine whether colesevelam slows or prevents progression of prediabetes to type 2 diabetes. (Endocr Pract. 2010;16:617-628)     

Pre-Conception Dyslipidemia Is Associated with Development of Preeclampsia and Gestational Diabetes Mellitus

IntroductionThe association between glucose intolerance, elevated blood pressure and abnormal lipid levels is well established and comprises the basis of metabolic syndrome pathophysiology. We hypothesize that abnormal preconception lipid levels are associated with the increased risk of severe pregnancy complications such as preeclampsia and gestational diabetes mellitus.MethodsWe included all singleton deliveries (n = 27,721) of women without known cardiovascular morbidity and preeclampsia and gestational diabetes mellitus during previous pregnancies. Association between preconception low high density lipoprotein cholesterol (HDLc level≤50 mg/dL), high triglycerides (level≥150 mg/dL) and the primary outcome (composite of gestational diabetes mellitus/or preeclampsia) was assessed using Generalized Estimation Equations.ResultsPrimary outcome of preeclampsia and/or gestational diabetes was observed in a total of 3,243 subjects (11.7%). Elevated triglycerides and low HDLc were independently associated with the primary outcome: with odds ratio (OR) of 1.61 (95% CI 1.29–2.01) and OR = 1.33 (95% CI 1.09–1.63), respectively, after adjusting for maternal age, weight, blood pressure, repeated abortions, fertility treatments and fasting glucose. There was an interaction between the effects of HDLc≤50 mg/dL and triglycerides≥150 mg/dL with an OR of 2.69 (95% CI 1.73–4.19).ConclusionsOur analysis showed an increased rate of preeclampsia and/or gestational diabetes in women with low HDLc and high triglycerides values prior to conception. In view of the severity of these pregnancy complications, we believe this finding warrants a routine screening for the abnormal lipid profile among women of a child-bearing age.     

Effect of Dexamethasone on Oral Glucose Tolerance in Healthy Adults

ObjectiveTo determine the dose-response and time course of action of a single dose of dexamethasone on plasma glucose and insulin dynamics in healthy adults.MethodsParticipants included healthy adults who met the following inclusion criteria: 18 to 65 years of age, body mass index of 18 to 25 kg/m2, no family history of diabetes mellitus, not taking any medication known to affect glucose tolerance, and nonpregnant state for female participants. Each participant underwent 3 sequential blocks of 75-g oral glucose tolerance tests (OGTTs) on days 1, 2, and 3; this sequence was repeated on 3 different occasions separated by more than 2 weeks. On the first day of each block, participants reported to the research center after a 10- to 12-hour overnight fast, and fasting baseline blood samples for glucose, insulin, and C-peptide were obtained. Baseline (0 mg) OGTT was then performed with a 75-g glucose load, and blood samples were collected at 30, 60, 90, and 120 minutes for measurements of glucose, insulin, and C-peptide. After the baseline OGTT on day 1, a single dose of either 2-, 4- or 8-mg of dexamethasone was administered orally. Twenty-four and 48 hours later, participants returned for additional OGTTs.ResultsTen healthy volunteers (4 male and 6 female) were enrolled. The effect of dexamethasone was maximal 24 hours after 8-mg dexamethasone compared with the effect observed after no dexamethasone administration. At 60 minutes during the OGTT (following 8-mg dexamethasone), blood glucose increased from 127 ± 7.1 mg/dL (6.35 ± 0.36 mmol/L) to 176 ± 19 mg/dL (8.8 ± 0.95 mmol/L), insulin increased from 49.3 ± 3.2 μIU/mL (342 ± 22 pmol/L) to 119.7 ± 10.1 μIU/mL (831 ± 70 pmol/L), and C-peptide increased from 6376 ± 510 pg/L (1913 ± 153 pmol/L) to 10 143 ± 1016 pg/L (3043 ± 305 pmol/L); the 60-minute levels returned towards baseline at 48 hours. Smaller changes were observed with 2- and 4-mg dexamethasone. Twenty-four hours after 8-mg dexamethasone, there was a 2.2- and 1.5-fold increase in homeostasis model assessment of insulin resistance and homeostasis model assessment of β cell, respectively, and a 2.5-fold decrease in the Matsuda sensitivity index.ConclusionsA single oral dose of 8-mg dexamethasone increases blood glucose, insulin, and C-peptide levels maximally at 24 hours, 1 hour following 75-g OGTT. A dexamethasone stress test might identify persons at increased risk for type 2 diabetes. (Endocr Pract. 2010:16:770-777)     

Deficiency of mast cells in coronary artery endarterectomy of male patients with type 2 diabetes

Background

Increased fasting plasma glucose (FPG), which includes impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and diabetes, is a risk factor for arterial stiffness. While IFG is widely accepted as a cardiovascular risk factor, recent studies have argued that subjects with high-normal glucose level were characterized by a high incidence of cardiovascular disease. The purpose of this study is to investigate the relationship between FPG and arterial stiffness in non-diabetic healthy subjects.

Methods

We recruited 697 subjects who visited the health promotion center of a university hospital from May 2007 to August 2008. Age, sex, body mass index (BMI), resting heart rate, smoking habits, alcohol intake, exercise, blood pressure, medical history, FPG, lipid profile, high sensitivity C-reactive protein (hs-CRP), and Brachial-ankle pulse wave velocity (ba-PWV) were measured. We performed correlation and multiple linear regression analyses to divide the research subjects into quartiles: Q1(n = 172), 65 mg/dL ≤FPG < 84 mg/dL; Q2(n = 188), 84 mg/dL ≤FPG < 91 mg/dl; Q3(n = 199), 91 mg/dL ≤FPG < 100 mg/dL; Q4(n = 138), 100 mg/dL ≤FPG < 126 mg/dL.

Results

FPG has an independent, positive association with ba-PWV in non-diabetic subjects after correcting for confounding variables, including age, sex, BMI, blood pressure, resting heart rate, hs-CRP, lipid profile, and behavioral habits. The mean ba-PWV of the high-normal glucose group (Q3, 1384 cm/s) was higher than that of the low-normal glucose group (1303 ± 196 cm/s vs.1328 ± 167 cm/s, P < 0.05). The mean ba-PWV value in the IFG group (1469 ± 220 cm/s) was higher than that in the normoglycemic group (P < 0.05, respectively).

Conclusions

An increase in FPG, even within the normal range, was associated with aggravated arterial stiffness. Further research is needed to determine the glycemic target value for the prevention of arterial stiffness in clinical and public health settings.     

Glucose dysregulation in obese children: predictive, risk, and potential protective factors

Objective: The aim of our study was to determine the prevalence of impaired glucose tolerance (IGT) and type 2 diabetes (DM2) in obese children and adolescents of Greek origin and compare our data with pertinent literature findings in an attempt to uncover predictive, risk, and preventive factors. Research Methods and Procedures: A total of 117 obese children and adolescents 12.1 ± 2.7 years old underwent a 2‐hour oral glucose tolerance test (OGTT). Insulin resistance (IR) and β‐cell function were estimated using the homeostasis model assessment (HOMA)‐IR and the insulinogenic index, respectively. Results: A total of 17 patients (14.5%) had IGT, and none had DM2. The overall prevalence rates of both IGT and DM2 in our subjects were lower than those reported in a recent multiethnic U.S. study. Nevertheless, the difference between our IGT data and those of the U.S. study was due mostly to the prepubertal subjects (9% vs. 25.4%), whereas no difference was observed in the pubertal population (18% vs. 21%). Fasting glucose, insulin, and HOMA‐IR values were not predictive of IGT. The absolute value of insulin at 2 hours of the OGTT combined with the time‐integrated glycemia (AUCG) can strongly predict IGT, whereas higher area under the curve for insulin (AUCI) values were found to be protective. Discussion: In ethnic groups less prone to diabetes development, IGT or DM2 in obese subjects is more likely to develop at puberty than at the prepubertal stage. It is advisable that physicians caring for obese adolescents perform an OGTT for early detection of IGT because HOMA‐IR values, although higher in IGT subjects and indicative of IR, cannot predict IGT.     

The relationship between fasting hyperglycemia and insulin secretion in subjects with normal or impaired glucose tolerance

To assess the relationship between the fasting plasma glucose (FPG) concentration and insulin secretion in normal glucose tolerance (NGT) and impaired glucose tolerance (IGT) subjects, 531 nondiabetic subjects with NGT (n = 293) and IGT (n = 238; 310 Japanese and 232 Mexican Americans) received an oral glucose tolerance test (OGTT) with measurement of plasma glucose, insulin, and C-peptide every 30 min. The insulin secretion rate was determined by plasma C-peptide deconvolution. Insulin sensitivity (Matsuda index) was measured from plasma insulin and glucose concentrations. The insulin secretion/insulin resistance (IS/IR) or disposition index was calculated as DeltaISR/DeltaG / IR. As FPG increased in NGT subjects, the IS/IR index declined exponentially over the range of FPG from 70 to 125 mg/dl. The relationship between the IS/IR index and FPG was best fit with the equation: 28.8 exp(-0.036 FPG). For every 28 mg/dl increase in FPG, the IS/IR index declined by 63%. A similar relationship between IS/IR index and FPG was observed in IGT. However, the decay constant was lower than in NGT. The IS/IR index for early-phase insulin secretion (0-30 min) was correlated with the increase in FPG in both NGT and IGT (r = -0.43, P < 0.0001 and r = -0.20, P = 0.001, respectively). However, the correlation between late-phase insulin secretion (60-120 min) and FPG was not significant. In conclusion, small increments in FPG, within the "normal" range, are associated with a marked decline in glucose-stimulated insulin secretion and the decrease in insulin secretion with increasing FPG is greater in subjects with NGT than IGT and primarily is due to a decline in early-phase insulin secretion.     

Characterizing Glucose Changes Antecedent to Hypoglycemic Events in the Intensive Care Unit

ObjectiveTo determine whether patterns of glucose changes before hypoglycemia vary according to the severity of the event.MethodsIn this retrospective analysis, point-ofcare blood glucose (POC-BG) data were obtained from the intensive care units (ICUs) of a convenience sample of hospitals that responded to a survey on inpatient diabetes management quality improvement initiatives. To evaluate POC-BG levels before hypoglycemic events, data from patients who experienced hypoglycemia during their time in the ICU were examined, and their glucose changes were assessed against a comparison group of patients who achieved a glycemic range of 80 to 110 mg/dL without ever experiencing hypoglycemia. Absolute glucose decrease, glucose rate of change, and glucose variability before hypoglycemic events (< 40, 40-49, 50-59, and 60-69 mg/ dL) were calculated.ResultsA total of 128 419 POC-BG measurements from 2942 patients in 89 ICUs were analyzed. Patients who experienced the most severe hypoglycemic episodes had the largest absolute drop in their glucose levels before the event (P < .001). The glucose rate of change before a hypoglycemic event increased with worsening hypoglycemia: mean (± standard deviation) glucose rate of change was-1.69 (± 2.98) mg/dL per min before an episode with glucose values less than 40 mg/dL, -0.56 (± 2.65) mg/dL per min before an episode with glucose values 60 to 69 mg/dL, but only -0.39 (± 0.70) for patients who attained a glucose range of 80 to 110 mg/dL without hypoglycemia (P < .001). Glucose variability before an event progressively increased with worsening biochemical hypoglycemia and was least among patients achieving glucose concentrations in the 80 to 110-mg/dL range without hypoglycemia (P < .001).ConclusionsAntecedent glucose change and variability were greater for patients who experienced hypoglycemia. If monitored, these patterns could potentially alert clinicians and help them take preventive measures. Further examination of how these parameters interact with other predisposing risk factors for hypoglycemia is warranted. (Endocr Pract. 2012;18:317-324)