2-hour Value Research Articles

Abdominal fat distribution and insulin resistance in Indian women with polycystic ovarian syndrome

The relationship between insulin resistance and abdominal fat distribution was studied in Indian patients with PCOS. Subcutaneous fat, together with a family history of type 2 diabetes mellitus, was the best marker of insulin resistance.

Reversal of Diuretic-Associated Impaired Glucose Tolerance and New-Onset Diabetes: Results of the STAR-LET Study

Reversal of new-onset diabetes secondary to thiazide diuretic use remains questionable. STAR-LET was a 6-month extension of the Study of Trandolapril/Verapamil SR and Insulin Resistance (STAR), which assessed the effects of a fixed-dose renin-angiotensin system inhibitor (RASI)/hydrochlorothiazide (HCTZ) combination on changes in 2-hour oral glucose tolerance test (OGTT) results. STAR-LET explored whether the glycemic impact of HCTZ could be reversed by conversion to a RASI/verapamil combination. The primary outcome was change in 2-hour OGTT results. Fifty-one percent of the STAR patients were enrolled in STAR-LET. The 2-hour OGTT value (mmol/L) was unchanged from STAR baseline in the RASI/verapamil group (7.7+/-2.4 vs 8.1+/-3.3; P=.18) and improved in those who were switched from RASI/HCTZ to RASI/verapamil (8.5+/-3.0 vs 7.2+/-2.3; P<.001). This exploratory study suggests that the impairment in glycemic control seen with use of a thiazide diuretic combined with a RASI can be reversed by switching to a regimen that does not include a diuretic.

At what fasting blood glucose should we recommend oral glucose tolerance test for the diagnosis of diabetes mellitus?

INTRODUCTION: At present, the oral glucose tolerance test (OGTT) is recommended for fasting plasma glucose of 110 to 125 mg/dl. We believe the actual burden of type 2 diabetes mellitus (T2 DM) might be under-estimated when OGTT is performed at that level. Hence we tried to Þ nd out fasting plasma glucose at which we need to request an OGTT to pick up more patients with impaired glucose tolerance and asymptomatic T2 DM. METHODOLOGY: We have analyzed consecutive 621 OGTTs in nonpregnant adults done in our hospital for diagnosis of diabetes. Patients were identiÞ ed from our hospital-computerized database, and data were collected from case notes and the laboratory reports. RESULTS: Putting fasting glucose in 5 mg cohort, we have noted a clear trend of raised 2-hour glucose value above 140 when fasting goes above 90 mg/dl. A similar phenomenon was noted when fasting went above 110; the 2-hour values also went above 200 mg/dl. This trend is not affected by the two important risk factors for diabetes, viz., family history and hypertension. CONCLUSION: In our study, a fasting glucose above 90 mg/dl increases the risk of abnormal 2-hour value. Therefore, we recommend OGTT when fasting glucose is more than 90 mg/dl for people from our part of the world to diagnose impaired glucose tolerance and asymptomatic T2 DM irrespective of risk factors.

The erythromycin breath test reflects P-glycoprotein function independently of cytochrome P450 3A activity

The erythromycin breath test (ERBT) has been widely used as a phenotypic measure of cytochrome P450 (CYP) 3A activity in individuals, as well as its modulation by inhibitors or inducers. However, it is not entirely clear what this measure actually reflects because, in addition to CYP3A, animal studies suggest that P-glycoprotein is also involved in erythromycin's hepatic disposition. Thus studies were undertaken to determine the effect of tariquidar, a potent P-glycoprotein inhibitor that does not affect CYP3A activity, on the ERBT and on the CYP3A-mediated metabolism of midazolam, a non-P-glycoprotein substrate. A randomized, double-blind, 2-way crossover trial was performed in 8 healthy subjects involving the intravenous administration of either placebo or tariquidar (150 mg over a period of 30 minutes) on 2 study days 2 weeks apart. On both days, a 1-hour ERBT was performed, followed by determination of midazolam's systemic clearance after a 1-mg intravenous dose. Tariquidar increased the ERBT 1-hour value in all subjects (median, 2.1% [interquartile range (IQR), 1.9% to 3.3%] versus 5.4% [IQR, 3.7% to 7.8%] for placebo and tariquidar, respectively; P = .012), representing a median 2.3-fold (IQR, 1.9- to 3.0-fold) increase. By contrast, midazolam's systemic clearance after tariquidar was unchanged (median change, -4.6% [IQR, -10.2% to 10.7%]; P = .78). Hepatic P-glycoprotein is an important determinant of the ERBT and a potentially confounding factor in interpreting the meaning of the trait measure. In addition, the results demonstrate the dynamic interplay between hepatic drug metabolism and transport of dual CYP3A/P-glycoprotein substrates.

Status of Glucose Metabolism and the Factors Affecting It, in Children with Thalassemia Major.

Abnormalities of the glucose metabolism are well documented in patients with Thalassemia Major who are frequently transfused and receiving therapy for chelation, due to excess iron deposition in the pancreas. The incidence of abnormalities in the glucose metabolism increase with age, with peak incidence between 16–20 years. The Indian (Asian) population is genetically predisposed to developing type 2 diabetes mellitus which is an additional risk factor for our Thalassemic population. Chelation is suboptimal in most of the patients due to economic reasons and ignorance. Impaired glucose tolerance (IGT) usually precedes the development of frank diabetes mellitus and intensive chelation in those with impaired glucose tolerance test may delay/prevent the onset of diabetes mellitus. Hence it is important to know the glyco-metabolic status of these children. At our Thalassemia endocrinology clinic, glucose tolerance test (GTT) is performed routinely in all subjects with Thalassemia major who have not already developed diabetes to identify the “at risk” population.GTT is performed by drawing a baseline fasting sample for blood glucose, oral glucose was given in a dose of 1.75mg/kg upto a maximum of 75 gms. Blood glucose level is measured 2 hours after oral glucose. According to the WHO criteria, Fasting plasma glucose between 110–126mg/dl is classified as impaired fasting and above 126mg/dl as diabetes. 2-hour plasma glucose value between 140–200mg/dl is classified as impaired glucose tolerance and above 200 mg/dl as diabetes. The purpose of this study was to analyze the status of the glucose metabolism of children and young adults with Thalassemia major who were attending our Thalassemia endocrinology clinic and to compare the factors affecting subjects with an abnormal glucose metabolism with those who have a normal glucose metabolism. The parameters compared were: effect of mean S. ferritin levels, age of onset of chelation and genetic predisposition. Retrospective analysis of our case records was done to determine the prevalence of diabetes and impaired glucose tolerance in children and young adults between 13 and 25 years of age. Of the 33 subjects evaluated, 16 out of 33 (48.5%) subjects had an abnormality of the glucose metabolism. 14/33 subjects (42.4%) had developed diabetes mellitus and 2 had an impaired GTT. Of the 16 affected subjects 9 were males and 7 were females (M:F = 1.28:1). The mean serum ferritin for this group was 5464ng/ml, 5503ng/ml for the diabetic group and 5425 for those with impaired GTT. (Range 2523–10904ng/ml). History of diabetes in a first or second degree relative was positive in 9 subjects(56.25%), negative in 2 and unknown in 5 subjects. Average age of onset of chelation was 8 years in this group. Oral glucose tolerance test was normal in 17/33(51.5%) subjects of which 10 were males and 7 were females (1.42:1). Average serum ferritin was 4747.4ng/ml in the group with a normal glucose tolerance. (1600–8294ng/ml). Family history of diabetes in a first or second degree relative was positive in 8 subjects(47%), negative in 4 and unknown in 5 subjects. Average age of onset of chelation was 6.5 years in the group with normal glucose metabolism. In conclusion of the 33 subjects evaluated, 48.5% had an abnormal glucose metabolism.

Prevalence of Abnormal Glucose Tolerance Following a Transient Ischemic Attack or Ischemic Stroke

Despite current preventive therapies, patients with transient ischemic attack (TIA) and ischemic stroke remain at high risk for recurrent brain disease and cardiovascular events. In an effort to develop new therapies, abnormal glucose tolerance has recently been proposed as an interventional target. Among persons not otherwise known to be diabetic, impaired glucose tolerance (IGT) and diabetic glucose tolerance (DGT) are each associated with an increased risk for incident vascular disease, vascular disease mortality, and all-cause mortality. We conducted this study to determine if IGT and DGT are sufficiently common among patients with TIA and ischemic stroke to warrant therapeutic trials of antihyperglycemic agents. Men and women older than 45 years were recruited from 3 hospitals in south central Connecticut. Eligibility criteria included a recent TIA or nondisabling ischemic stroke, no history of physician-diagnosed diabetes mellitus, and a fasting plasma glucose level less than 126 mg/dL (<7.0 mmol / L). After an overnight fast, subjects were admitted to a clinical research center for a standard 75-g oral glucose tolerance test. Impaired glucose tolerance was defined by a 2-hour plasma glucose value of 140 to 199 mg/dL (7.8-11.0 mmol / L) and DGT by a value of 200 mg/dL or greater (> or =11.1 mmol/L). Between June 2000 and August 2003, we enrolled 98 eligible patients. The average time from TIA or stroke to measurement of glucose tolerance was 105 days (range, 24-180 days) and the median age was 71 years. Twenty-seven subjects (28%) had IGT and 24 (24%) had diabetes. In a forward stepwise logistic regression model, only a fasting plasma glucose level of 110 mg/dL or greater (> or =6.1 mmol / L) and lower waist circumference were associated with an increased risk for IGT or DGT. Impaired glucose tolerance and DGT are present in most persons with a recent TIA or ischemic stroke who have no history of diabetes and a fasting plasma glucose level less than 126 mg/dL (<7.0 mmol / L). Our findings bring new urgency to the initiation of research to examine the effectiveness of antihyperglycemic therapies among patients with cerebrovascular disease and abnormal glucose tolerance.

Insulin Resistance and Risk of Congestive Heart Failure

Diabetes and obesity are established risk factors for congestive heart failure (CHF) and are both associated with insulin resistance. To explore if insulin resistance may predict CHF and may provide the link between obesity and CHF. The Uppsala Longitudinal Study of Adult Men, a prospective, community-based, observational cohort in Uppsala, Sweden. We investigated 1187 elderly (>or=70 years) men free from CHF and valvular disease at baseline between 1990 and 1995, with follow-up until the end of 2002. Variables reflecting insulin sensitivity (including euglycemic insulin clamp glucose disposal rate) and obesity were analyzed together with established risk factors (prior myocardial infarction, hypertension, diabetes, electrocardiographic left ventricular hypertrophy, smoking, and serum cholesterol level) as predictors of subsequent incidence of CHF, using Cox proportional hazards analyses. First hospitalization for heart failure. One hundred four men developed CHF during a median follow-up of 8.9 (range, 0.01-11.4) years. In multivariable Cox proportional hazards models adjusted for established risk factors for CHF, increased risk of CHF was associated with a 1-SD increase in the 2-hour glucose value of an oral glucose tolerance test (hazard ratio [HR], 1.44; 95% confidence interval [CI], 1.08-1.93), fasting serum proinsulin level (HR, 1.29; 95% CI, 1.02-1.64), body mass index (HR, 1.35; 95% CI, 1.11-1.65), and waist circumference (HR, 1.36; 95% CI, 1.10-1.69), whereas a 1-SD increase in clamp glucose disposal rate decreased the risk (HR, 0.66; 95% CI, 0.51-0.86). When adding clamp glucose disposal rate to these models as a covariate, the obesity variables were no longer significant predictors of subsequent CHF. Insulin resistance predicted CHF incidence independently of established risk factors including diabetes in our large community-based sample of elderly men. The previously described association between obesity and subsequent CHF may be mediated largely by insulin resistance.

Postoperative Parathyroid Hormone Levels in Conjunction with Corrected Calcium Values as a Predictor of Post-Thyroidectomy Hypocalcemia: Review of Outcomes 1 Year after the Implementation of a New Protocol

To determine the effectiveness of post-thyroidectomy parathyroid hormone (PTH) levels in conjunction with corrected calcium values as predictors of patients at risk of developing hypocalcemia. This is a follow-up study reviewing the results of a newly implemented post-thyroidectomy algorithm. The changes in management from the previous protocol involve decision making based on the 12-hour corrected calcium and PTH levels, as well as the 1-hour PTH value. The study involved 120 patients separated into two groups: 60 prior to implementation of the protocol and 60 following the implementation of the protocol. Patients having completion thyroidectomy, neck dissections, or parathyroidectomy were excluded. Since the implementation of the new protocol, there has been a reduction in the rate of transient hypocalcemia (25% to 12%; p = .059), fewer blood tests (23 to 15 per patient), and earlier patient discharges. The new algorithm is effective in detecting patients who are not at risk of developing hypocalcemia at 12 hours. This has led to significant cost savings at our institution. Moreover, calcium supplementation based on the 1-hour PTH level has coincided with a reduction in cases of transient hypocalcemia.

Fetal Hyperinsulinism and Maternal One-Hour Postload Plasma Glucose Level

Fetal insulin concentrations reflect the intrauterine glucose load given the fetus by the mother. In this study, we assessed the association between maternal glucose levels during oral glucose tolerance testing and fetal cord insulin. Pregnant women with an oral glucose tolerance test (OGTT) result were included in this prospective study. The patients were divided into 3 groups according to their 1-hour OGTT glucose concentration: up to 160 mg/dL (control, group I), 160-179 mg/dL (intermediate, group II), and gestational diabetes mellitus (GDM, group III). Patients with GDM were assigned to insulin therapy if blood glucose levels were not in the preferable range. Of the 930 patients who entered the study, 570 (61.3%) were assigned to group I, 76 (8.2%) to group II, and 284 (30.5%) to group III. The cord blood insulin value was significantly (P < .001, Mann-Whitney test) higher in group II (median, 12.8 microU/mL; range, 3-130 microU/mL) than in group I (median, 7.25 microU/mL; range, < 3-98 microU/mL). Cord blood insulin values were higher, albeit not significantly (P = .100, Mann-Whitney test), in group II than in group III (median, 9.9 microU/mL; range, < 3-61 microU/mL). Children whose mothers had a 1-hour value between 160 and 179 mg/dL had significantly higher cord blood insulin values than offspring of women with a 1-hour value below 160 mg/dL.

Estrogen replacement treatment in diabetic ovariectomized female rats potentiates postischemic leukocyte adhesion in cerebral venules.

Chronic 17beta-estradiol (E2) replacement therapy in ovariectomized (OVX) female rats reduces leukocyte adhesion and brain damage after transient forebrain ischemia. Recently, we found that E2 treatment in diabetic OVX females was associated with enhanced postischemic neuropathology. We tested the hypothesis that in chronically hyperglycemic diabetic OVX females, chronic E2 replacement potentiates post-transient forebrain ischemia leukocyte adhesion. Pial venules were observed through closed cranial windows. Adherence of rhodamine 6G-tagged leukocytes was monitored before and 10 hours after transient forebrain ischemia (20 minutes right common carotid artery occlusion plus hemorrhagic hypotension) in intact, untreated OVX and E2-treated OVX females rendered diabetic via streptozotocin. Leukocyte adhesion was quantitated as the percentage venular area occupied by adherent leukocytes. At 2 hours after transient forebrain ischemia, a similar low level of leukocyte adhesion was seen in the 3 groups (<3% of the venular area). Starting at approximately 4 hours after ischemia, leukocyte adhesion in the E2-treated OVX females rose to significantly higher levels compared with the other groups. Relative to the 2-hour value, the level of adhesion at 10 hours was 12.5-fold, 4-fold, and 5-fold greater in the E2-treated OVX, OVX, and intact groups, respectively. Leukocyte extravasation (beginning after 6 hours of reperfusion) was observed in a majority (64%) of the E2-treated animals, with limited or no extravasation seen in the intact or OVX groups. These results suggest that factors associated with diabetes and chronic hyperglycemia convert E2 from a counterinflammatory to a proinflammatory substance in an ischemic setting.

Delta creatine kinase–MB outperforms myoglobin at two hours during the emergency department identification and exclusion of troponin positive non–ST-segment elevation acute coronary syndromes

Study objectiveLimited information is available about the diagnostic performance of creatine kinase (CK)–MB and myoglobin levels during the early evaluation of chest pain patients using cardiac troponins as the criterion standard for diagnosing acute myocardial infarction. In this study, we compare the sensitivity and specificity of the baseline, 2-hour absolute, and 2-hour delta values of myoglobin and CK-MB mass assay for detection of acute myocardial infarction using cardiac troponin I (troponin) as the sole marker of myocardial necrosis. MethodsA prospective observational study was conducted of 975 chest pain patients with a baseline troponin level of 1.0 ng/mL or less (Abbott Axsym Assay) and an initial ECG nondiagnostic for injury. CK-MB, myoglobin, and troponin levels were all measured on the Abbott Axsym immunoassay. Acute myocardial infarction was diagnosed if there was at least 20 minutes of chest pain and any one of the following criteria within 24 hours of ED presentation: a serial increase in troponin to more than 1.0 ng/mL, new Q-wave formation in 2 contiguous leads, or patient death by cardiac or unknown cause. The optimal values of CK-MB and myoglobin were chosen at the most accurate value on the receiver operating characteristic (ROC) curve (ie, value with lowest false-negative and false-positive rate) of the 2-hour absolute and 2-hour delta value for predicting acute myocardial infarction. ResultsAcute myocardial infarction was diagnosed in 44 (4.5%) of the 975 study patients. ROC curve analysis revealed no statistically significant differences in areas for myoglobin and CK-MB values at baseline and 2 hours for determination of acute myocardial infarction. However, the ROC curve area of the delta CK-MB level significantly outperformed the ROC curve area of the delta myoglobin level for early identification of acute myocardial infarction (0.97 versus 0.81; 95% confidence interval [CI] for difference between areas 0.09 to 0.24). At the most accurate cutoff value, a 2-hour delta CK-MB level more than 0.7 ng/mL had a sensitivity of 93.2% (95% CI 81.3% to 98.5%), a specificity of 94.4% (95% CI 92.7% to 95.8%), a positive likelihood ratio of 16.7, and a negative likelihood ratio of 0.07. ConclusionA 2-hour delta CK-MB level outperforms myoglobin level in the early identification and exclusion of acute myocardial infarction in non–ST-segment elevation chest pain patients. This finding suggests that myoglobin may no longer be the optimal early marker of acute myocardial infarction when troponins are used as the criterion standard.

A Postnatal Fasting Plasma Glucose Is Useful in Determining Which Women With Gestational Diabetes Should Undergo a Postnatal Oral Glucose Tolerance Test

Obstetrical & Gynecological Survey: January 2004 - Volume 59 - Issue 1 - p 21-23 doi: 10.1097/01.OGX.0000102785.53063.66

Does maternal glucose intolerance affect the length of gestation in singleton pregnancies?

This study determined whether maternal glucose tolerance has a progressive effect on the length of gestation in singleton pregnancies and whether there is an increasing tendency towards spontaneous preterm birth with increasing glucose intolerance. A total of 2,168 consecutive Chinese women with singleton pregnancies who underwent the 75-g oral glucose tolerance test (OGTT) over a 24-month period were categorized by their OGTT 2-hour value (mmol/L) into the following six groups: 5.9 or less, 6.0-6.9, 7.0-7.9, 8.0-8.9, 9.0-10.9, and 11.0 or greater mmol/L. Women with a 2-hour glucose value of 8.0 or more mmol/L were considered to have gestational diabetes mellitus (GDM) and received diet treatment. Women who eventually required insulin were excluded from the final analysis. The mean gestational age, birth weight, incidence of preterm birth, large for gestational age (LGA, birth weight > 90th percentile), and macrosomic (birth weight > or = 4.0 kg) infants were compared among the six groups. The incidence of preterm birth correlated significantly with increasing glucose intolerance. On further analysis, incidence of spontaneous birth before 37 weeks in the lowest to the highest 2-hour value groups was as follows: 5.5%, 2.6%, 3.7%, 4.9%, 8.5%, and 10.3% (P =.015) and that before 32 weeks went from 0.4%, 0.3%, 0.8%, 0.4%, 2.2%, to 3.4% (P =.018), respectively. There was no significant difference in the incidence of LGA or macrosomic infants. Regression analysis confirmed that the OGTT 2-hour glucose value was an independent determinant of gestational length. Gestational glucose intolerance affects gestation length and incidence of preterm birth, which should be considered a confounding factor in the analysis of the neonatal outcome of GDM pregnancies.

The threshold criteria for the 75g oral glucose tolerance test in pregnancy and short-term adverse pregnancy outcomes

The significant threshold values for the 75g oGTT during pregnancy have yet to be conclusively determined. The study aimsto identify the risk significance of a borderline oGTT result. Women undergoing a 75g OGTT during the third trimester ofpregnancy were classified into two groups - borderline tolerance (2-h post-load glucose 8.0-8.5 mmol/l: n=75), and GDM(≥8.6 mmol/l: n=236). Outcome indicators of these two groups of women were compared to the parameters of the womenwith a presumed normal carbohydrate metabolism (n = 12185). GDM women showed themselves to be at a significantlyincreased risk of developing hypertensive disorders during pregnancy and to require obstetric intervention in the form ofinduction of labour and caesarean section. Their infants were more likely to be macrosomic or preterm and having a lowApgar score at birth. Shoulder dystocia was similarly more likely in infants born to GDM mothers. Women with borderlineglucose tolerance did not in any way show any statistically significant increased predisposition to these complications. Itwould appear the significant threshold for the 75g oGTT during pregnancy should be of the order proposed by the AmericanDiabetes Association criteria where the 2-hour post-load glucose value is ≥ 8.6 mmol/l.

Rate and risk factors of hypoglycemia in large-for-gestational-age newborn infants of nondiabetic mothers

Objective: The purpose of this study was to investigate the rate of hypoglycemia in large-for-gestational-age infants of nondiabetic mothers in relation to maternal or neonatal risk factors. Study Design: Hospital charts of all term large-for-gestational-age infants born between 1994 and 1998 (n = 1136) were analyzed for the rate of neonatal hypoglycemia (capillary glucose level, ≤30 mg/dL) during the first 24 hours of life. Infants of women with preexisting or gestational diabetes mellitus were excluded (n = 180). Neonatal glucose testing was performed at 1 or 2 hours of life, with subsequent measurements every 4 to 6 hours. Maternal and neonatal parameters were compared between neonates with and without hypoglycemia, including recent oral glucose tolerance test values in those women who were tested (n = 358). Results: Of 956 infants, 69 infants (7.2%) were not tested for hypoglycemia. In the remaining 887 infants, hypoglycemia occurred in 142 infants (16%) within the first 24 hours of life. The incidence of hypoglycemia decreased sharply during the first few hours of life, from 9.2% within the first hour of life, to 3.5% between 2 to 5 hours (cumulative) of life, and 2.4% between 6 and 24 hours of life. Gestational age at delivery was the only neonatal parameter that differed significantly between infants with and without hypoglycemia (39.5 vs 39.3 weeks, P =.01). The antenatal 1-hour oral glucose tolerance test value was the only predictive maternal parameter (141.5 vs 163.0 mg/dL, P <.006). There was an incremental risk of hypoglycemia with increasing 1-hour oral glucose tolerance test values, with hypoglycemia rates of 2.5%, 9.3%, 22.0%, and 50.0% that were associated with maternal 1-hour glucose values of <120, 120-179, 180-239, and ≥240 mg/dL, respectively (P <.05, for all comparisons). Conclusion: Routine glucose testing is indicated in large-for-gestational-age newborn infants of nondiabetic mothers. The 1-hour glucose value of the maternal oral glucose tolerance test is a fairly good predictor of subsequent neonatal hypoglycemia. A single elevated 1-hour value of ≥180 mg/dL markedly increases the risk of neonatal hypoglycemia. (Am J Obstet Gynecol 2002;187:913-7.)

Gestational Diabetes mellitus and Neonatal Hyperthyrotropinemia

Objective: To determine whether gestational diabetes mellitus (GDM) is associated with increased incidence of neonatal hyperthyrotropinemia. Study Design: In a retrospective study, maternal characteristics, infant outcome and cord blood thyrotropin (TSH) concentration were compared between 469 diet-treated GDM pregnancies diagnosed by the World Health Organization 75 g oral glucose tolerance test (OGTT) with 474 non-diabetic pregnancies with normal OGTT results. Results: Hyperthyrotropinemia (TSH >16 mIU/l) was found in 7.2% of the GDM pregnancies and 2.1% of the controls (p < 0.001), but there was no difference in the birth weight or gestational age. The TSH concentration was correlated with the OGTT 2-hour glucose value (ρ = 0.0948, p = 0.029) and Apgar score at the fifth minute (ρ = –0.1197, p = 0.009). There was no difference in the TSH or free thyroxine concentrations between the hyperthyrotropinemic newborns of the GDM and control groups. In the GDM group, the hyperthyrotropinemic newborns had a higher incidence (p = 0.017) of neonatal jaundice. Conclusions: Neonatal hyperthyrotropinemia is more frequently found in pregnancies with GDM, and this could have reflected increased fetal in-utero hypoxic stress in these pregnancies.

Identification of persons at high risk for type 2 diabetes mellitus: do we need the oral glucose tolerance test?

The standard method of identifying persons at high risk for type 2 diabetes mellitus involves detection of impaired glucose tolerance, which requires a costly and inconvenient 2-hour oral glucose tolerance test. Because clinical trials have indicated that diabetes is preventable by using behavioral or pharmacologic interventions, less expensive methods of identifying high-risk persons are needed. To determine whether multivariable models are superior to glucose tolerance tests for identifying persons at high risk for diabetes mellitus. Prospective cohort study. San Antonio, Texas. 1791 Mexican Americans and 1112 non-Hispanic whites without diabetes at baseline who were randomly selected from census tracts. Medical history; body mass index; blood pressure; fasting and 2-hour plasma glucose levels; fasting serum total, low-density lipoprotein, and high-density lipoprotein cholesterol levels; and triglyceride level. For prediction of 7.5-year incidence of type 2 diabetes, the area under the receiver-operating characteristic (ROC) curve for a multivariable model involving readily available clinical variables was significantly (P < 0.001) greater than the area under the ROC curve for the 2-hour glucose value alone (84.3% vs. 77.5%). Impaired glucose tolerance represents a single point on the latter curve. Adding the 2-hour glucose measurement to the multivariable model increased the area under its ROC curve, but only from 84.3% to 85.7%. Persons at high risk for diabetes mellitus are better identified by using a simple prediction model than by relying exclusively on the results of a 2-hour oral glucose tolerance test. Although adding the 2-hour glucose variable to the model enhanced prediction, the resulting slight improvement entails greater cost and inconvenience.

Glucose intolerance in cystic fibrosis patients.

Diabetes mellitus has evolved as a complication because of increased longevity of patients with cystic fibrosis (CF). CF-related diabetes (CFRD) is associated with increased morbidity and mortality, therefore, prompt diagnosis and aggressive management are important. The prevalence of CFRD increases with age with an age-dependent incidence rate of 5% per year; at 30 years 50% of patients are diabetic. CFRD develops insidiously. Screening by measurements of fasting, random plasma glucose or glycated haemoglobin A(1c), alone or in combination, do not reliably identify CFRD as compared with the 2-hour plasma glucose value measured during an oral glucose tolerance test. Reasons for the development of CFRD are not fully understood. Generally, patients are characterised by the presence of a class I, II or III CF mutation, exocrine pancreatic insufficiency, impaired and delayed insulin secretion, impaired glucagon secretion, normal insulin sensitivity and an increased insulin clearance rate. One can speculate that for endocrine dysfunction to deteriorate from normal to impaired glucose tolerance and then to CFRD, there must be an additional diabetes mellitus-related genetic defect.CFRD leads to deterioration of overall clinical CF status but insulin therapy can revert this. Late diabetic complications may develop as in other types of diabetes although macrovascular complications are rare. CFRD patients have an increased mortality compared to non-diabetic CF patients. Insulin therapy is the preferred treatment.

Intracellular skeletal muscle glucose metabolism is differentially altered by dexamethasone treatment of normoglycemic relatives of type 2 diabetic patients.

Young first-degree relatives of type 2 diabetic patients are insulin-resistant, with the insulin resistance mainly located in skeletal muscle due to decreased insulin-induced nonoxidative glucose metabolism and muscle glycogen synthase activation. We investigated whether the mechanism differs for dexamethasone (dex)-induced insulin resistance in first-degree relatives of type 2 diabetics versus healthy control subjects by quantifying intracellular glucose processing in muscle biopsies taken before and after 5 days of dex treatment (4 mg/d) in 20 normal glucose-tolerant relatives of type 2 diabetic patients and 20 matched controls (age, 29.4 +/- 1.7 v 29.4 +/- 1.6 years; body mass index, 25.1 +/- 1.0 v 25.1 +/- 0.9 kg/m2). In addition, an intravenous glucose tolerance test (IVGTT) combined with continuous indirect calorimetry was performed. Following 5 days of dex treatment, glucose tolerance deteriorated in both the relatives and the control subjects. Fasting dry-weight muscle glucose and fasting intracellular muscle glucose concentrations increased in response to dex only in the relatives (2.43 +/- 0.21 v 2.97 +/- 0.26 mmol/kg dry weight, P < .05; 0.28 +/- 0.07 v 0.45 +/- 0.08 mmol/L intracellular water, P < .05); no increases were observed in the control subjects. Fasting dry-weight muscle lactate also increased post-dex only in the relatives (7.37 +/- 0.40 v 10.77 +/- 1.22 mmol/kg dry weight, P < .001). Both basal muscle glucose and lactate concentrations from the IVGTT study correlated with the 2-hour post-dex glucose value obtained during the OGTT study in the relatives (R = .76 and R = .74, respectively, both P < .0001) but not in the control subjects. Basal intramuscular glycogen synthase activity decreased approximately 25% in both the relatives and control subjects post-dex; the decrement was significant (P < .01) only in control subjects. Indirect calorimetry during the post-dex IVGTT demonstrated increased glucose oxidation (P < .03) and reduced lipid oxidation (P < .03) in the relatives only. We postulate that the insulin resistance induced by dex in first-degree relatives of type 2 diabetic patients is associated with a preferential channeling of glucose into the glycolytic pathway (increased glucose oxidation and lactate production), probably associated with a preexisting downregulation of the glycosen synthase pathway.

Effects of new criteria for type 2 diabetes on the rate of postpartum glucose intolerance in women with gestational diabetes

Objective: Our purpose was to determine the impact of the 1997 American Diabetes Association diagnostic criteria for type 2 diabetes mellitus on the rate of postpartum glucose intolerance in women with gestational diabetes. Study Design: Women identified as having gestational diabetes were instructed to undergo a 75-g, 2-hour glucose tolerance test 4 to 6 weeks after delivery. The results were retrospectively categorized with both the 1979 National Diabetes Data Group criteria and those recommended by the American Diabetes Association in 1997. Results: Though the rate of overt diabetes mellitus did not increase when the 1997 American Diabetes Association criteria were used (7.8% vs 5.6%, P = not significant), the rate of impaired glucose metabolism was higher (20.1% vs 5%, P < .001). Most women (28/30, 93%) with a nondiagnostic glucose tolerance test result by the older criteria had abnormal results by the newer criteria. Fifty women had abnormalities of glucose metabolism under 1997 American Diabetes Association criteria; 34% of these women had fasting plasma glucose values in the normal range. Of the 25 women with impaired glucose tolerance, 16 (64%) had only an abnormal 2-hour value, with normal fasting glucose values. Conclusions: The rate of postpartum abnormalities in glucose metabolism more than doubles when the 1997 American Diabetes Association criteria are applied; more women are identified with lesser degrees of impairment. However, relying on fasting glucose levels alone, without glucose tolerance testing, may miss one third of women with such abnormalities. (Am J Obstet Gynecol 1999;181:610-4.)