Patterns of changes in fasting plasma glucose, hemoglobin A1c and the area under the curve during oral glucose tolerance tests in prediabetic subjects: results from a 16-year prospective cohort study among first-degree relatives of type 2 diabetic patients.

AIM: This study aimed to identify the patterns of changes in glycemic indices over time in prediabetics and to classify these subjects as either having a high or low risk for developing diabetes in future. METHODS: This prospective 16-year cohort study was conducted among 1228 prediabetic subjects. Three measurements including first visit, mean values during the follow-up period, and last visit from fasting plasma glucose (FPG), glycosylated hemoglobin (HbA1C), and area under the curve during an oral glucose tolerance test (OGTT AUC) were used to evaluate the patterns of changes by using the latent Markov model (LMM). RESULTS: The mean (standard deviation) age of subjects was 44.0 (6.8) years, and 73.6% of them were female. The LMM identified 2 latent states of subjects in terms of changes in FPG, HbA1c, OGTT AUC, and the combination of these glycemic measures: a low tendency to progress diabetes and a high tendency to progress diabetes with the latent state sizes (87, 13%), (94, 6%), (57, 43%), and (84, 16%), respectively. The LMM showed that the probability of transitioning from a low tendency to a high tendency to progress diabetes was higher than the probability of transitioning in the opposite direction. CONCLUSION: Based on a long-term evaluation of patterns of changes in glycemic indices, we classified prediabetic subjects into 2 groups (high or low risk to progress diabetes states in future). Also, the method used enabled us to estimate the transition probabilities from low- to high-risk states and vice versa. Our results reemphasized the values of all 3 glycemic measures in clinical settings for identifying prediabetic people with a high risk of progressing diabetes and the need for more effective prevention strategies, which should be conducted as urgently in prediabetic life as high-risk subjects.

Associations of sleep duration, sedentary behaviours and energy expenditure with maternal glycemia in pregnancy.

BACKGROUND: Women with high levels of physical activity (PA) are less likely to develop gestational diabetes mellitus (GDM), but the relations with sleep and sedentary behaviours (SB) are more controversial. We aimed to investigate all three components (sleep, PA, and SB) and their association with maternal glucose in pregnancy. METHODS: We included 766 pregnant women recruited at first trimester and that we followed at second trimester. We collected blood samples, anthropometry and standardized questionnaires about lifestyle including PA, SB, and sleep duration at both visits. Women completed a 50 g glucose challenge test at first trimester and 75-g oral glucose tolerance test (OGTT) at second trimester. We conducted regression analyses to test cross-sectional associations between sleep, PA, and SB with maternal glucose levels while taking into account potential confounders (maternal age, pre-pregnancy body mass index (BMI), gravidity, and smoking). We considered linear and quadratic relationships. RESULTS: At first trimester, we observed a linear relationship between shorter sleep duration and higher glucose levels, which was attenuated after adjustments for confounders. At second trimester, we found a quadratic relationship between sleep and glucose showing lowest levels at fasting and 1 h-post OGTT for women who slept 6-10 h/night. This association remained significant after adjusting for confounders and taking into account PA and/or SB. Greater amount of SB was associated with higher 1 h-glucose after adjustment for confounders (ß = 0.132; SE = 0.047; P = 0.005). CONCLUSIONS: Sleep duration is associated with glucose regulation in pregnancy, independently of PA and SB, and this association varies according to the period of gestation.

Continuous glucose monitoring guided insulin therapy is associated with improved clinical outcomes in cystic fibrosis-related diabetes.

INTRODUCTION: Continuous glucose monitoring (CGM) allows assessment of day to day glycaemic excursions and detects early glucose handling abnormalities that may not be apparent on oral glucose tolerance testing (OGTT). However, there is little published evidence as to whether these early dysglycaemic changes are amenable to treatment. We present outcomes following CGM guided insulin initiation at our centre. METHODS: Adults without a prior diagnosis of cystic fibrosis related diabetes (CFRD) whom underwent >72 h CGM at our adult CF centre were included in the study. Clinical outcomes including weight and pulmonary function changes over the next 12 months were compared between groups based on CGM results and subsequent management. RESULTS: CGM profiles for 59 patients were analysed. Insulin was commenced in 37 patients who had evidence of hyperglycaemia on CGM. Significant improvements in mean [95% confidence intervals] forced expiratory volume in 1 s (FEV1) (+4.3% predicted [1.06-7.48], p = 0.01) and weight (+1.2 kg [0.32-2.15], p = 0.01) were observed at 3 months in the insulin group. Annual rate of pulmonary function decline was also improved following insulin initiation. CONCLUSION: Insulin treatment targeted towards glycaemic excursions seen on CGM is associated with improvements in lung function and weight with subsequent reduced pulmonary function decline.

Optimal cut-off points of fasting plasma glucose for two-step strategy in estimating prevalence and screening undiagnosed diabetes and pre-diabetes in Harbin, China.

To identify optimal cut-off points of fasting plasma glucose (FPG) for two-step strategy in screening abnormal glucose metabolism and estimating prevalence in general Chinese population. A population-based cross-sectional study was conducted on 7913 people aged 20 to 74 years in Harbin. Diabetes and pre-diabetes were determined by fasting and 2 hour post-load glucose from the oral glucose tolerance test in all participants. Screening potential of FPG, cost per case identified by two-step strategy, and optimal FPG cut-off points were described. The prevalence of diabetes was 12.7%, of which 65.2% was undiagnosed. Twelve percent or 9.0% of participants were diagnosed with pre-diabetes using 2003 ADA criteria or 1999 WHO criteria, respectively. The optimal FPG cut-off points for two-step strategy were 5.6 mmol/l for previously undiagnosed diabetes (area under the receiver-operating characteristic curve of FPG 0.93; sensitivity 82.0%; cost per case identified by two-step strategy ¥261), 5.3 mmol/l for both diabetes and pre-diabetes or pre-diabetes alone using 2003 ADA criteria (0.89 or 0.85; 72.4% or 62.9%; ¥110 or ¥258), 5.0 mmol/l for pre-diabetes using 1999 WHO criteria (0.78; 66.8%; ¥399), and 4.9 mmol/l for IGT alone (0.74; 62.2%; ¥502). Using the two-step strategy, the underestimates of prevalence reduced to nearly 38% for pre-diabetes or 18.7% for undiagnosed diabetes, respectively. Approximately a quarter of the general population in Harbin was in hyperglycemic condition. Using optimal FPG cut-off points for two-step strategy in Chinese population may be more effective and less costly for reducing the missed diagnosis of hyperglycemic condition.

Screening practices for identifying type 2 diabetes in adolescents.

OBJECTIVE: To characterize pediatrician and family physician (FP) screening practices for type 2 diabetes among adolescents and to examine the impact of the 2010 American Diabetes Association (ADA) guidelines, recommending use of Hemoglobin A1c (HbA1c). METHODS: We conducted a cross-sectional mail survey of a random sample of 1,400 U.S. pediatricians and FPs and we received 604 eligible responses. Our main outcome measure was the types of tests ordered by physicians, particularly HbA1c, when presented with a hypothetical scenario. RESULTS: The overall response rate was 52% (57% for pediatricians and 48% for FPs). Fasting glucose and HbA1c were the most commonly ordered tests. Overall, at least 58% of physicians ordered HbA1c; 35% ordered HbA1c in conjunction with fasting tests; and 22% ordered HbA1c alone or with nonfasting tests. Only 38% of providers were aware of the new ADA recommended HbA1c screening guidelines. However, a majority (67%) said they would change their screening practices. In the context of the guidelines, 84% of physicians would now order HbA1c. Furthermore, there was a large increase in the proportion of physicians who would shift to using HbA1c only or with other nonfasting tests. CONCLUSIONS: When screening adolescents for type 2 diabetes, providers are more likely to order HbA1c and order fewer fasting tests in response to the new ADA guidelines. HbA1c has lower sensitivity and higher costs than other testing modalities in children, therefore increasing uptake of this test (HbA1c) in children may have implications for both detection rates and healthcare costs.

Diagnostic performance of using one- or two-HbA1c cut-point strategies to detect undiagnosed type 2 diabetes and impaired glucose regulation within a multi-ethnic population.

INTRODUCTION: We compared test performance and cost per case for strategies detecting diabetes on the oral glucose tolerance test (OGTT) using either (a) glycated haemoglobin (HbA1c) ≥ 6.5% (48 mmol/mol) or (b) two HbA1c thresholds where the first cut-point 'rules out' and the second 'rules in' diabetes. HbA1c values in between the thresholds require confirmatory glucose testing for diagnosis. MATERIALS AND METHODS: We conducted an analysis of adults aged 40-75 years from the Leicester Ethnic Atherosclerosis and Diabetes Risk (LEADER) cohort (Leicester, UK), from 2002 to 2008, who underwent oral glucose tolerance testing (OGTT) and HbA1c testing. RESULTS: From 8696 individuals (mean age 57.3 years, 73% white Europeans (WE) and 27% South Asians (SA)), HbA1c ≥ 6.5% produced sensitivity of 62.1% for detecting diabetes in WE and 78.9% in SA. Using two selected thresholds, HbA1c ≤ 5.8% (rule-in, 40 mmol/mol) and HbA1c ≥ 6.8% (rule-out, 51 mmol/mol) produced high sensitivity/specificity (> 91.0%) for detecting diabetes, however, 28.8% of the cohort with HbA1c 5.9%-6.7% required a subsequent glucose test. The two cut-point threshold produced a lower cost per case of diabetes detected in WE, compared to HbA1c ≥ 6.5% of £38.53 (1.89 to 86.81) per case, but was more expensive in SA by £84.50 (69.72 to 100.92) per case. Using a risk score to determine HbA1c testing, the same costs per case became £63.33 (23.33 to 113.26) in WE and £69.21 (55.60 to 82.41) in SA. CONCLUSION: Using a two-threshold strategy may have some benefits over a single cut-point; however, 28.8% of individuals required two blood tests.

Tests and expenditures in the initial evaluation of peripheral neuropathy.

BACKGROUND: Peripheral neuropathy is a common disorder in which an extensive evaluation is often unrevealing. METHODS: We sought to define diagnostic practice patterns as an early step in identifying opportunities to improve efficiency of care. The 1996-2007 Health and Retirement Study Medicare claims-linked database was used to identify individuals with an incident diagnosis of peripheral neuropathy using International Classification of Diseases, Ninth Revision, codes and required no previous neuropathy diagnosis during the preceding 30 months. Focusing on 15 relevant tests, we examined the number and patterns of tests and specific test utilization 6 months before and after the incident neuropathy diagnosis. Medicare expenditures were assessed during the baseline, diagnostic, and follow-up periods. RESULTS: Of the 12, 673 patients, 1031 (8.1%) received a new International Classification of Diseases, Ninth Revision, diagnosis of neuropathy and met the study inclusion criteria. Of the 15 tests considered, a median of 4 (interquartile range, 2-5) tests were performed, with more than 400 patterns of testing. Magnetic resonance imaging of the brain or spine was ordered in 23.2% of patients, whereas a glucose tolerance test was rarely obtained (1.0%). Mean Medicare expenditures were significantly higher in the diagnostic period than in the baseline period ($14,362 vs $8067, P < .001). CONCLUSIONS: Patients diagnosed as having peripheral neuropathy typically undergo many tests, but testing patterns are highly variable. Almost one-quarter of patients receiving neuropathy diagnoses undergo high-cost, low-yield magnetic resonance imaging, whereas few receive low-cost, high-yield glucose tolerance tests. Expenditures increase substantially in the diagnostic period. More research is needed to define effective and efficient strategies for the diagnostic evaluation of peripheral neuropathy.

Mechanism-based population modelling for assessment of L-cell function based on total GLP-1 response following an oral glucose tolerance test.

GLP-1 is an insulinotropic hormone that synergistically with glucose gives rise to an increased insulin response. Its secretion is increased following a meal and it is thus of interest to describe the secretion of this hormone following an oral glucose tolerance test (OGTT). The aim of this study was to build a mechanism-based population model that describes the time course of total GLP-1 and provides indices for capability of secretion in each subject. The goal was thus to model the secretion of GLP-1, and not its effect on insulin production. Single 75 g doses of glucose were administered orally to a mixed group of subjects ranging from healthy volunteers to patients with type 2 diabetes (T2D). Glucose, insulin, and total GLP-1 concentrations were measured. Prior population data analysis on measurements of glucose and insulin were performed in order to estimate the glucose absorption rate. The individual estimates of absorption rate constants were used in the model for GLP-1 secretion. Estimation of parameters was performed using the FOCE method with interaction implemented in NONMEM VI. The final transit/indirect-response model obtained for GLP-1 production following an OGTT included two stimulation components (fast, slow) for the zero-order production rate. The fast stimulation was estimated to be faster than the glucose absorption rate, supporting the presence of a proximal-distal loop for fast secretion from L: -cells. The fast component (st3) = 8.64·10⁻5 [mg⁻¹]) was estimated to peak around 25 min after glucose ingestion, whereas the slower component (st4 = 26.2·10⁻5 [mg⁻¹]) was estimated to peak around 100 min. Elimination of total GLP-1 was characterised by a first-order loss. The individual values of the early phase GLP-1 secretion parameter (st3) were correlated (r = 0.52) with the AUC(0-60 min.) for GLP-1. A mechanistic population model was successfully developed to describe total GLP-1 concentrations over time observed after an OGTT. The model provides indices related to different mechanisms of subject abilities to secrete GLP-1. The model provides a good basis to study influence of different demographic factors on these components, presented mainly by indices of the fast- and slow phases of GLP-1 response.

Assessment of insulin resistance and impaired glucose tolerance in lean women with polycystic ovary syndrome.

OBJECTIVE: To analyze insulin resistance (IR) and determine the need for a 2-hour oral glucose tolerance test (OGTT) for the identification of IR and impaired glucose tolerance (IGT) in lean nondiabetic women with polycystic ovary syndrome (PCOS). METHODS: This was a cross-sectional analysis of treatment-naive women with PCOS who enrolled in a university-based clinical trial. Nondiabetic women with PCOS based on the Eunice Kennedy Shriven National Institute of Child Health and Human Development (NICHD) definition, aged 18-43 years and weighing ≤113 kg, were evaluated. Glucose and insulin levels were assessed at times 0, 30, 60, 90, and 120 minutes after a 75-g glucose load. Lean was defined as body mass index (BMI) <25 kg/m(2). Multiple linear regression was performed. RESULTS: A cohort of 78 women was studied. The prevalence of IR was 0% among lean women vs. 21% among nonlean subjects based on fasting insulin I(0) and 40%-68% based on two different homeostatic model assessment (HOMA) cutoff points (p < 0.005). All women with IR had a BMI ≥ 28. Controlling for age and race, BMI explained over 57% of the variation in insulin fasting (I(o)), glucose fasting/Io (G(o)/I(o)), the qualitative insulin sensitivity check index (QUICKI), and HOMA and was a highly significant predictor of these outcomes (p < 0.0001). Only 1 of 31 (3%) of the lean PCOS women had IGT based on a 2-hour OGTT, and no lean subjects had IGT based on their fasting blood glucose. CONCLUSIONS: Diabetes mellitus, IGT, and IR are far less common in young lean women with PCOS compared with obese women with PCOS. These data imply that it is unnecessary to routinely perform either IR testing or 2-hour OGTT in lean women with PCOS; however, greater subject accumulation is needed to determine if OGTT is necessary in lean women with PCOS. BMI is highly predictive of both insulin and glucose levels in women with PCOS.

Population and individual minimal modeling of the frequently sampled insulin-modified intravenous glucose tolerance test.

Population approaches are more robust estimators of insulin sensitivity (SI) and glucose effectiveness (SG) with the minimal model of glucose kinetics during an intravenous glucose tolerance test (IVGTT). We assessed the performance of 3 population methods, iterative two-stage (ITS), Bayesian hierarchical Markov chain Monte Carlo (MCMC), and NONMEM first-order conditional estimation (FOCE) with interaction (NM), and made a comparison with the standard two-stage method (STS) employing the weighted nonlinear regression analysis. To evaluate accuracy of individual and population estimates, 40 simulated insulin-modified frequently sampled IVGTTs (IM-FSIVGTT) were derived from real IM-FSIVGTTs (0.3 g glucose per kg body weight with 0.02 U/kg insulin at 20 minutes; 30 samples over 180 minutes) performed in 40 healthy Caucasian subjects (male/female, 22/18; age, 46 +/- 9 years; body mass index [BMI], 26.7 +/- 5.7 kg. m(-2); mean +/- SD). The population methods assumed a log-normal population distribution of parameters. All methods gave a similar but overestimated population SG by 9% to 13%. Population SI was underestimated to a different degree by the methods (STS 6%, ITS 10%, MCMC 13%, and NM 7%). The between-subject variability of SG was overestimated by STS and underestimated by the population methods (true 33%, STS 40%, ITS 19%, MCMC 24%, NM 24%; coefficient of variation). For SI, this quantity was well estimated by all methods (true 79%, STS 80%, ITS 82%, MCMC 83%, NM 82%). The results for individual estimates indicate that STS performs better than the population methods when estimating SI (STS 12%, ITS 16%, MCMC 16%, NM 16%; 1 outlying subject excluded; root mean squared error expressed as percent of mean) but worse for SG (STS 28%, ITS 21%, MCMC 20%, NM 19%). We conclude that the robust performance of population approaches, preventing parameter estimation failures associated with the nonlinear regression analysis, is not required with IM-FSIVGTT in subjects with normal glucose tolerance. The standard two-stage technique is the preferred method under such circumstances.

Healthcare access and utilization among women 40 and older at the U.S.-Mexico border: predictors of a routine check-up.

Mexican Americans are more likely to experience barriers to access and utilization of healthcare services than any other U.S. Hispanic group. In Mexico, where the majority of the population has access to care, the pressing issue is the underutilization of preventive services among adults. This study was conducted to assess access and utilization barriers among a U.S.-Mexico border population. A cross-sectional, population-based survey was conducted during 1999-2000 in a pair of contiguous U.S.-Mexico border communities. Household surveys were administered to U.S. and Mexican women, 40 years of age and older, to assess healthcare access and utilization, participation in chronic disease screenings, orientation toward prevention and personal history of chronic disease. Analysis indicates few statistically significant differences (p < 0.05) among access and utilization variables by country. Mexican participants were more likely to have a regular source of care and to have had a blood sugar test within the past 12 months. U.S. participants more often reported having had a Pap smear and mammogram during the previous year. Factors independently positively associated with having had a routine check-up during the past 12 months included age and having a regular provider or place to go when sick. Only going to the doctor when ill was independently inversely associated with routine check-ups in the past 12 months. Findings suggest that U.S. and Mexican border populations are similar with regard to healthcare access and utilization characteristics. Efforts to increase utilization of preventive health screenings among women are needed at the U.S.-Mexico border.

Reconstructing insulin secretion rate after a glucose stimulus by an improved stochastic deconvolution method.

Reconstructing insulin secretion rate (ISR) after a glucose stimulus by deconvolution is difficult because of its biphasic pattern, i.e., a rapid secretion peak is followed by a slower release. Here, we refine a recently proposed stochastic deconvolution method by modeling ISR as the multiple integration of a white noise process with time-varying statistics. The unknown parameters are estimated from the data by employing a maximum likelihood criterion. A fast computational scheme implementing the method is presented. Monte Carlo simulation results are developed which numerically show a more reliable ISR profile reconstructed by the new method.

Glucose effectiveness and insulin sensitivity from the minimal models: consequences of undermodeling assessed by Monte Carlo simulation.

The unlabeled (cold) minimal model (MM) and the labeled (hot) minimal model (HMM) are a powerful tool to investigate in vivo metabolism from a standard intravenous glucose tolerance test (IVGTT) or hot IVGTT (HIVGTT). They allow to estimate metabolic indexes of the glucose-insulin system, namely glucose effectiveness (GE) and insulin sensitivity (IS) (of uptake and production those of MM, and of uptake only those of HMM). Here, the consequences of the single-compartment glucose kinetics approximation used in the MM's are investigated via Monte Carlo simulation, using a physiologic reference model (RM) of the system. RM allows to generate noisy synthetic plasma concentrations of glucose, tracer glucose, and insulin during IVGTT and HIVGTT, which are then analyzed with MM and HMM. The MM and HMM GE and IS are then compared with the RM ones. Results of 400 runs show that: 1) correlation of MM GE with the RM index is weak; 2) MM IS is well correlated with the RM index, but severely underestimates it; 3) HMM clearance rate is correlated with RM clearance; and 4) HMM IS is well correlated and only slightly overestimates the RM index. These results demonstrate that GE of MM is most affected by the single-compartment approximation and the indexes of HMM are more robust than those of MM.

A stochastic deconvolution method to reconstruct insulin secretion rate after a glucose stimulus.

Insulin secretion rate (ISR) is not directly measurable in man but it can be reconstructed from C-peptide (CP) concentration measurements by solving an input estimation problem by deconvolution. The major difficulties posed by the estimation of ISR after a glucose stimulus, e.g., during an intravenous glucose tolerance test (IVGTT), are the ill-conditioning of the problem, the nonstationary pattern of the secretion rate, and the nonuniform/infrequent sampling schedule. In this work, a nonparametric method based on the classic Phillips-Tikhonov regularization approach is presented. The problem of nonuniform/infrequent sampling is addressed by a novel formulation of the regularization method which allows the estimation of quasi time-continuous input profiles. The input estimation problem is stated into a Bayesian context, where the a priori known nonstationary characteristics of ISR after the glucose stimulus are described by a stochastic model. Deconvolution is tackled by linear minimum variance estimation, thus allowing the derivation of new statistically based regularization criteria. Finally, a Monte-Carlo strategy is implemented to assess the uncertainty of the estimated ISR arising from CP measurement error and impulse response parameters uncertainty.

Valores alterados en la curva de tolerancia a la glucosa en relación a indicadores de riesgo en mujeres no gestantes / Alteration of the glucose tolerance test in relation to risk factors in non pregnant women

La diabetes mellitus cobra cada vez más importancia como problema de salud pública en México, por lo que es muy importante implementar métodos de tamizaje sencillos, baratos y aplicables en niveles de atención primaria. Es el objetivo de este informe presentar el análisis de las curvas de tolerancia a la glucosa de un grupo de 109 mujeres no gestantes pertenecientes a la cohorte de estudios perinatales del Instituto Nacional de Perinatología. El análisis está dirigido a la búsqueda del tiempo post carga que más frecuentemente sobrepasa los límites de glucemia normales, así como su relación con indicadores clínicos de riesgo, con la finalidad de buscar el tiempo post carga que más verdaderos positivos detecte. Se estudió un grupo de 109 mujeres cuyos diagnósticos se realizaron a través de una curva de tolerancia a la glucosa: 25 casos resultaron con diabetes mellitus o intolerancia a la glucosa y 84 casos sin alteración en el metabolismo de la glucosa. Se evaluó edad, antecedentes familiares de diabetes en padre y/o madre, número de gestaciones menos abortos, así como porcentaje de pesos para la talla. El análisis se hizo a través de frecuencias proporciones y pruebas de ji-cuadrada. Se encontró que el tiempo de post carga a las 2 horas detectó casi el doble de casos que la hora post carga (0.92 vs 0.48 respectivamente) con diferencias estadísticamente significativas (ji-cuadrada 81.28 p<0.001), por lo que se concluye que al menos para la población que se estudió las 2 horas es el mejor tiempo de detección. De los indicadores de riesgo evaluados, fueron el sobrepeso ò 127 por ciento de peso para la talla y la edad ò 33 años los indicadores que marcaron diferencias estadísticamente significativas entre el grupo de mujeres con diagnóstico de alteración contra las que no presentaron (ji-cuadrada 8.99 y 8.34 p <0.01)

Gestational diabetes in Papua New Guinea.

Pacific populations have some of the highest prevalences for diabetes in the world. Whilst universal screening for diabetes in pregnancy does yield the best pick-up rate it is not economically feasible in developing countries. Traditional risk factors have increasingly been shown to miss most gestational diabetes, particularly in populations for whom family history is unknown and obstetrical history not recorded. This study shows genetic origin to be a potent marker for gestational diabetes in a Pacific Island population. It is recommended that in Port Moresby 'at-risk ethnicity' (urban Motuan or Marshall Lagoon origin) be added to the list of indications for antenatal glucose tolerance testing in Papua New Guinean women.

[Life expectancy and risk assessment in decreased glucose tolerance (subclinical diabetes)]. / Lebenserwartung und Risikoeinschätzung bei verminderter Glukosetoleranz (subklinischer Diabetes).

The term Impaired Glucose Tolerance (IGT) has replaced the term Subclinical Diabetes (SD). It corresponds to a grey zone between normal glucose tolerance (GT) and diabetic glucose intolerance which by definition can be determined only by an oral glucose tolerance test. Pathogenetically, and impaired glucose tolerance constitutes a risk factor for the formation of atherosclerosis and in about 30% of cases represents a pre-stage of diabetes mellitus. No mortality statistics are as yet available for insureds with impaired glucose tolerance. We may, however, assume with good reason that their relative mortality lies between the comparable values of insureds with normal glucose tolerance and those with type 2 diabetes. The relative mortality of type 2 diabetes is calculated on the basis of the American Medical Impairment Study 1983 and the Swiss Re study on diabetes mellitus and the relative mortality of insureds with impaired glucose tolerance is then determined on that basis. Finally, a possible course of action for the risk assessment of applicants with impaired glucose tolerance is proposed and the expected extra mortality rates are given.