The 75-g glucose tolerance test in pregnancy: a reference range determined on a low-risk population and related to selected pregnancy outcomes

OBJECTIVE: To determine a reference range for the 75-g glucose tolerance test (GTT) in pregnancy using a group of women at low risk for gestational diabetes mellitus (GDM) and to determine the validity of this reference range by examining selected pregnancy outcomes for glucose-tolerant women with a 2-h result on the GTT up to 1.0 mmol/l below the diagnostic level for GDM compared with treated women with GDM. RESEARCH DESIGN AND METHODS: The reference range for the GTT was determined in 573 Caucasian women with an age <25 years and a BMI of <25 kg/m2. Selected pregnancy outcomes were compared between 272 treated women with GDM (diagnosed on the basis of a 2-h glucose level > or =8.0 mmol/l) and 308 women with a 2-h glucose level of 7.0-7.9 mmol/l. RESULTS: There was 95% confidence that at least 95% of all the fasting glucose levels are < or =5.1 mmol/l(92 mg/dl) and 95% confidence that at least 95% of all the 2-h glucose levels were < or =7.8 mmol/l (140 mg/dl). Treated women with GDM had a significantly reduced rate of large-for-gestational-age infants compared with glucose-tolerant women, without any increase in the rate of small-for-gestational-age infants or obstetric interventions. CONCLUSIONS: The reference range for the GTT in pregnancy should be determined on a low-risk population rather than on a total population. Consideration should be given to lowering the fasting glucose level to 5.0 mmol/l (90 mg/dl) and the 2-h level to 7.8 mmol/ (140 mg/dl). Glucose-tolerant women below this relatively low reference range have an increased rate of large-for-gestational-age infants and may benefit from treatment.     

The diagnosis of "pathological hyperglycaemia' in gestational diabetes in a high risk obstetric population

In order to define a level of "pathological hyperglycaemia', i.e. glucose intolerance that predicts perinatal morbidity among the obstetric population, 100 g glucose tolerance tests (GTTs) were performed in 660 patients attending for antenatal care at the University Hospital in Jeddah. The results were analysed in two ways: (1) patients were stratified according to the number of abnormal glucose values on the GTTs and (2) patients were placed into one of three groups according to the 100 g GTT diagnostic criteria, i.e. normal (non-GDM), abnormal with fasting blood glucose (FBG) > or = 5.8 mmol l-1 (GDM), and abnormal with FBG < 5.8 mmol l-1 (gestational induced hyperglycaemia, GIH). Although there was a stepwise association between fetal/maternal morbidity with increasing number of abnormal glucose values, no level of glucose intolerance could be defined as a threshold level for normal response. However, when stratified by FBG, GDM patients were significantly heavier (78.5 kg +/- SD 14.9), had a higher incidence of both macrosomia (27.5%) and operative delivery (25.3%) than the other two groups (14.7%, 14.3%, and 15.4%, 12.8% in the non-GDM and GIH, respectively). It is suggested that among patients with abnormal GTT results a FBG > or = 5.8 mmol l-1 identifies a threshold for true "pathological hyperglycaemia'.     

Gestational diabetes mellitus and subsequent development of overt diabetes mellitus

GDM develops in 1-3% of all pregnancies. Women with GDM are characterized by a relatively diminished insulin secretion coupled with a pregnancy-induced insulin resistance primary located in skeletal muscle tissue. The cellular background for this insulin resistance is not known. The binding of insulin to its receptor and the subsequent activation of the insulin receptor tyrosine kinase have significant importance for the cellular effect of insulin. Thus, the pathogenesis to the insulin resistance was studied by investigating insulin receptor binding and tyrosine kinase activity in skeletal muscle biopsies from women with GDM and pregnant controls. No major abnormalities were found in GDM wherefore it is likely that the insulin resistance is caused by intracellular defects distal to the activation of the tyrosine kinase. Glucose tolerance returns to normal postpartum in the majority of women with GDM. However, previous studies, in populations quite different from a Danish population, have shown that women with previous GDM have a high risk of developing overt diabetes mellitus later in life. Hence, we aimed to investigate the prognosis of women with previous GDM with respect to subsequent development of diabetes and also to identify predictive factors for the development of overt diabets in these women. A follow-up study of diet treated GDM women diagnosed during 1978 to 1985 at the Rigshospital, Copenhagen was performed. Glucose tolerance was evaluated in 241 women (81% of the GDM population) 2-11 years after pregnancy. Abnormal glucose tolerance was found in 34.4% of the women (3.7% IDDM, 13.7% NIDDM, 17% IGT) in contrast to a control group where none had diabetes and 5.3% had IGT. Logistic regression analysis identified the following independent risk factors for later development of diabetes: a high fasting glucose level at diagnosis of GDM, a delivery more than 3 weeks before term, and an abnormal OGTT 2 months postpartum. Low insulin secretion at diagnosis of GDM was also an independent risk factor. The presence of ICA and GAD-autoantibodies in pregnancy was associated with later development of IDDM. In another study the following techniques: hyperinsulinaemic euglycaemic clamp, indirect calorimetry and tritiated glucose infusion were used to evaluate insulin sensitivity in glucose tolerant nonobese women with previous GDM and controls. A decreased insulin sensitivity due to a decreased non-oxidative glucose metabolism in skeletal muscle was found in women with previous GDM. Hence, the activity of three key enzymes in intracellular glucose metabolism (GS, HK and PFK) was studied in skeletal muscle biopsies obtained in the basal state and after 3 h hyperinsulinaemia, with the aim to identify the cellular defects causing the decreased insulin sensitivity. However, no abnormalities in enzyme activity was found. The same group of previous GDM women had a relatively reduced insulin secretion evaluated by the IVGTT. A longitudinal study of 91 GDM women showed a relatively reduced insulin secretion to oral glucose in pregnancy, postpartum as well as 5-11 years later. Thus the present review has shown that even nonobese glucose tolerant women with previous GDM are characterized by the metabolic profile of NIDDM i.e. insulin resistance and impaired insulin secretion. Hence, the combination of this finding together with the significantly increased risk for development of diabetes indicates that all women with previous GDM should have a regular assessment of their glucose tolerance in the years after pregnancy. The first OGTT should be performed around 2 months postpartum in order to diagnose women already diabetic and to identify women with the highest risk for later development of overt diabetes. Women with previous GDM comprise a target group for future intervention trials with the aim to prevent or delay development of NIDDM and IDDM.     

Threshold value of glucose screening tests in pregnancy: could it be standardized for every population?

We aimed to determine a threshold value that perfectly demarcates women at high risk for gestational diabetes mellitus (GDM) in the Turkish population. One thousand gravid women of 24 to 32 weeks of gestation were given 50 g, 1-hour glucose screening tests. A 100 g, 3-hour glucose tolerance test (GTT) was performed on all patients whose screening test plasma glucose value was 130 mg/dL or greater. The sensitivity and specificity of each screening test value was found, and the GDM rate of each value was calculated. Three-hundred-and-five patients were identified for GTT and 66 were shown to have GDM with two or more abnormal values in GTT. The incidence of GDM was found to be 6.6%. The maximum specificity and sensitivity were met at 140 mg/dL. However, this value underestimated 12% of patients with GDM, and the lowest value for a positive GTT appeared to be 134 mg/dL. We recommend a 135 mg/dL threshold for GTT since this threshold accurately diagnoses almost all women with GDM while eliminating unnecessary GTT.     

The STOP-NIDDM Trial: an international study on the efficacy of an alpha-glucosidase inhibitor to prevent type 2 diabetes in a population with impaired glucose tolerance: rationale, design, and preliminary screening data. Study to Prevent Non-Insulin-Dependent Diabetes Mellitus

OBJECTIVE: To describe the rationale and design, and to discuss the preliminary screening data, of the Study to Prevent NIDDM (STOP-NIDDM Trial), an international study on the efficacy of the alpha-glucosidase inhibitor acarbose in preventing or delaying the development of type 2 diabetes in a population with impaired glucose tolerance (IGT). RESEARCH DESIGN AND METHODS: A total of 1,418 subjects diagnosed with IGT according to the World Health Organization's criteria and having a fasting plasma glucose concentration > or =5.6 mmol/L were randomized in a double-blind fashion to receive either acarbose (100 mg t.i.d.) or placebo for a predictive median follow-up period of 3.9 years. The primary outcome is the development of type 2 diabetes diagnosed using a 75-g oral glucose tolerance test according to the new criteria. The secondary outcomes are changes in blood pressure, lipid profile, insulin sensitivity, cardiovascular events, and morphometric profile. RESULTS: Screening was performed in a high-risk population. As of 1 March 1997, 4,424 subjects had been screened, and data were available for 3,919 (88.5%) subjects. Of these subjects, 1,200 (30.6%) had glucose intolerance. Of the subjects with glucose intolerance, 521 (13.3%) had previously undetected type 2 diabetes, and 679 (17.3%) had IGT. Of the IGT population, 412 (60.7%) subjects were eligible for the study This population had the following characteristics: the mean age was 54.8 years, 52% of the subjects were female, 53% had more than one risk factor for type 2 diabetes, >90% had a family history of diabetes, 78.2% had a BMI > or =27 kg/m2, 47.5% had high blood pressure, 51.2% had dyslipidemia, and 22.8% of the women had a history of gestational diabetes. CONCLUSIONS: Screening of a high-risk population yields one eligible subject per every 10 volunteers screened. This study should definitely answer the question of whether acarbose can prevent or delay the progression of IGT to type 2 diabetes mellitus.     

Gestational diabetes: antepartum characteristics that predict postpartum glucose intolerance and type 2 diabetes in Latino women

We examined antepartum clinical characteristics along with measures of glucose tolerance, insulin sensitivity, pancreatic beta-cell function, and body composition in Latino women with gestational diabetes mellitus (GDM) for their ability to predict type 2 diabetes or impaired glucose tolerance (IGT) within 6 months after delivery. A total of 122 islet cell antibody-negative women underwent oral and intravenous glucose tolerance tests (OGTT; IVGTT), hyperinsulinemic-euglycemic clamps, and measurement of body fat between 29 and 36 weeks' gestation and returned between 1 and 6 months postpartum for a 75-g OGTT. Logistic regression analysis was used to examine the relationship between antepartum variables and glucose tolerance status postpartum. At postpartum testing, 40% of the cohort had normal glucose tolerance, 50% had IGT, and 10% had diabetes by American Diabetes Association criteria. Independent antepartum predictors of postpartum diabetes were the 30-min incremental insulin:glucose ratio during a 75-g OGTT (P = 0.0002) and the total area under the diagnostic 100-g glucose tolerance curve (P = 0.003). Independent predictors of postpartum IGT were a low first-phase IVGTT insulin response (P = 0.0001), a diagnosis of GDM before 22 weeks' gestation (P = 0.003), and weight gain between prepregnancy and the postpartum examination (P = 0.03). All subjects had low insulin sensitivity during late pregnancy, but neither glucose clamp nor minimal model measures of insulin sensitivity in the 3rd trimester were associated with the risk of IGT or diabetes within 6 months' postpartum. These results highlight the importance of pancreatic beta-cell dysfunction, detectable under conditions of marked insulin resistance in late pregnancy, to predict abnormalities of glucose tolerance soon after delivery in pregnancies complicated by GDM. Moreover, the association of postpartum IGT with weight gain and an early gestational age at diagnosis of GDM suggests a role for chronic insulin resistance in mediating hyperglycemia outside the 3rd trimester in women with such a beta-cell defect.     

Glucagon-like peptide 1 improves the ability of the beta-cell to sense and respond to glucose in subjects with impaired glucose tolerance

Impaired glucose tolerance (IGT) and NIDDM are both associated with an impaired ability of the beta-cell to sense and respond to small changes in plasma glucose concentrations. The aim of this study was to establish if glucagon-like peptide 1 (GLP-1), a natural enteric peptide and potent insulin secretagogue, improves this defect. Two weight-matched groups, one with eight subjects having IGT (2-h glucose, 10.1 +/- 0.3 mmol/l) and another with seven subjects with diet-treated NIDDM (2-h glucose, 14.5 +/- 0.9 mmol/l), were studied on two occasions during a 12-h oscillatory glucose infusion, a sensitive test of the ability of the beta-cell to sense and respond to glucose. Glucose was infused with a mean rate of 4 mg x kg(-1) x min(-1), amplitude 33% above and below the mean rate, and periodicity of 144 min, with infusion of saline or GLP-1 at 0.4 pmol x kg(-1) x min(-1) for 12 h. Mean glucose levels were significantly lower in both groups during the GLP-1 infusion compared with during saline infusion: 9.2 +/- 0.4 vs. 6.4 +/- 0.1 mmol/l in the IGT subjects (P < 0.0004) and 14.6 +/- 1.0 vs. 9.3 +/- 0.7 mmol/l in NIDDM subjects (P < 0.0002). Despite this significant reduction in plasma glucose concentration, insulin secretion rates (ISRs) increased significantly in IGT subjects (513.3 +/- 77.6 vs. 583.1 +/- 100.7 pmol/min; P < 0.03), with a trend toward increasing in NIDDM subjects (561.7 +/- 122.16 vs. 642.8 +/- 128 pmol/min; P = 0.1). These results were compatible with enhanced insulin secretion in the presence of GLP-1. Spectral power was used as a measure of the ability of the beta-cell to secrete insulin in response to small changes in the plasma glucose concentration during the oscillatory infusion. Spectral power for ISR increased from 2.1 +/- 0.9 during saline infusion to 7.4 +/- 1.3 during GLP-1 infusion in IGT subjects (P < 0.004), but was unchanged in NIDDM subjects (1.0 +/- 0.4 to 1.5 +/- 0.6; P = 0.3). We concluded that low dosage GLP-1 improves the ability of the beta-cell to secrete insulin in both IGT and NIDDM subjects, but that the ability to sense and respond to subtle changes in plasma glucose is improved in IGT subjects, with only a variable response in NIDDM subjects. Beta-cell dysfunction was improved by GLP-1 infusion, suggesting that early GLP-1 therapy may preserve beta-cell function in subjects with IGT or mild NIDDM.     

Vascular endothelial growth factor is essential for corpus luteum angiogenesis

OBJECTIVE: To compare within-subject variability of plasma glucose measured 2 h after a glucose tolerance test (GTT) with that of plasma glucose measured 2 h after administration of a standardized test meal (diabetes screening product [DSP], Ceapro, Edmonton, Alberta, Canada) and to determine the relationship between the two sets of plasma glucose measurements. RESEARCH DESIGN AND METHODS: Plasma glucose and insulin responses of 36 overnight-fasted subjects (10 lean normal, 9 obese normal, 9 with impaired glucose tolerance [IGT], and 8 with mild diabetes) were studied on eight different mornings after they consumed 75 g oral glucose or 50 g carbohydrate from the DSP. Each test meal was repeated four times by each subject. Within-subject coefficients of variation (CVs) (CV = 100 x SD/mean) of plasma glucose concentrations 2 h after administration of the GTT and DSP were compared by repeated measures ANOVA and linear regression analysis. RESULTS: Mean plasma glucose 2 h after administration of the DSP (D) was linearly related to that 2 h after the GTT (G): G = 1.5 x D - 1.6 (r = 0.97, P < 0.0001). The CV of 2-h plasma glucose was significantly lower after administration of the DSP, 10.5 +/- 1.0%, than after the GTT, 12.7 +/- 1.18% (P = 0.025). The effect of test meal on CV differed in different groups of subjects (P = 0.018), with the largest difference found in IGT subjects, in whom the CV after DSP administration was 47% less than after the GTT (P = 0.0005). The DSP was significantly more palatable and produced fewer adverse symptoms than the GTT. CONCLUSIONS: Plasma glucose concentrations measured 2 h after DSP administration are closely related to those measured 2 h after the GTT but are more consistent than the 2-h post-GTT concentrations within the critical IGT range. This finding suggests that measurement of plasma glucose 2 h after administration of the DSP may allow more precise discrimination among normal glucose levels, IGT, and diabetes than measurement of plasma glucose 2 h after the GTT.     

Prevalence and incidence of NIDDM in Daqing City

OBJECTIVE: To investigate the prevalence and incidence of non-insulin dependent diabetes (NIDDM) in China by WHO criteria. METHODS: In the prevalence survey of NIDDM all 110660 participants (55391 men, 53269 women) were inhabitants of Daqing City, the largest oil center in northeast China, accounting for 87.3% of the 25 to 74 aged population in this city. They were screened by measuring two-hour plasma glucose concentrations (PG2 h) after a breakfast containing at least 80 g of carbohydrate, then a standard oral glucose tolerance test (OGTT, 75 g glucose load) was performed in 4209 subjects with PG2 h more than 6.67 mmol/L in this screen. NIDDM and impaired glucose tolerance (IGT) were diagnosed using WHO criteria. Incidence survey was made in 36471 non-diabetics identified in the prevalence survey. Two-hour urine-glucose after breakfast was determined during first screen. The urine-glucose trace or positive subjects were then followed by OGTT. Glucose was measured by glucose oxidation method. RESULTS AND CONCLUSIONS: In prevalence survey, 630 newly diagnosed NIDDM (296 males, 334 females) and 596 IGT (318 males, 278 females) were found in 110660 (male:female = 55391/53269) studied subjects in addition to 190 previously diagnosed NIDDM. Thus the total prevalence of NIDDM was 7.7/1000, and IGT was 5.5/1000. Standardized to the Chinese population in 1982, the prevalences are 12.6/1000 (95% CI = 12.0/1000-13.3/1000) and 7.7/1000 (95% CI = 7.16/1000-8.19/1000) respectively. In the incidence survey, 191 NIDDM (103 males, 88 females) were diagnosed in the 36471 (male:female = 18801/17670) non-diabetics from 1986 to 1990, thus the annual incidence of NIDDM was 131/100000 (137 males, 125 females). Standardized incidence is 131/100000 (95% CI = 94/100000-168/ 100000). It is estimated that there would be more than 700 thousand new diabetics per year in 24-74 years old Chinese if Chinese population were 1.3 billion in the early 21st century.     

Treatment with the oral antidiabetic agent troglitazone improves beta cell responses to glucose in subjects with impaired glucose tolerance

Impaired glucose tolerance (IGT) is associated with defects in both insulin secretion and action and carries a high risk for conversion to non-insulin-dependent diabetes mellitus (NIDDM). Troglitazone, an insulin sensitizing agent, reduces glucose concentrations in subjects with NIDDM and IGT but is not known to affect insulin secretion. We sought to determine the role of beta cell function in mediating improved glucose tolerance. Obese subjects with IGT received 12 wk of either 400 mg daily of troglitazone (n = 14) or placebo (n = 7) in a randomized, double-blind design. Study measures at baseline and after treatment were glucose and insulin responses to a 75-g oral glucose tolerance test, insulin sensitivity index (SI) assessed by a frequently sampled intravenous glucose tolerance test, insulin secretion rates during a graded glucose infusion, and beta cell glucose-sensing ability during an oscillatory glucose infusion. Troglitazone reduced integrated glucose and insulin responses to oral glucose by 10% (P = 0.03) and 39% (P = 0.003), respectively. SI increased from 1.3+/-0.3 to 2.6+/-0.4 x 10(-)5min-1pM-1 (P = 0.005). Average insulin secretion rates adjusted for SI over the glucose interval 5-11 mmol/liter were increased by 52% (P = 0.02), and the ability of the beta cell to entrain to an exogenous oscillatory glucose infusion, as evaluated by analysis of spectral power, was improved by 49% (P = 0.04). No significant changes in these parameters were demonstrated in the placebo group. In addition to increasing insulin sensitivity, we demonstrate that troglitazone improves the reduced beta cell response to glucose characteristic of subjects with IGT. This appears to be an important factor in the observed improvement in glucose tolerance.     

Defects in insulin secretion and action in women with a history of gestational diabetes

Gestational diabetes mellitus (GDM) is associated with defects in insulin secretion and insulin action, and women with a history of GDM carry a high risk for the development of non-insulin-dependent diabetes mellitus (NIDDM). Assessment of subjects with a history of GDM who are currently normoglycemic should help elucidate some of the underlying defects in insulin secretion or action in the evolution of NIDDM. We have studied 14 women with normal oral glucose tolerance who had a history of GDM. They were compared with a group of control subjects who were matched for both body mass index (BMI) and waist-to-hip ratio (WHR). All subjects underwent tests for the determination of oral glucose tolerance, ultradian oscillations in insulin secretion during a 28-h glucose infusion, insulin secretion in response to intravenous glucose, glucose disappearance after intravenous glucose (Kg), and insulin sensitivity (SI) as measured by the Bergman minimal model method. The BMI in the post-GDM women was similar to that in the control subjects (24.9 +/- 1.2 vs. 25.4 +/- 1.4 kg/m2, respectively), as was the WHR ratio (0.80 +/- 0.01 vs. 0.76 +/- 0.01, respectively). The post-GDM women were slightly older (35.2 +/- 0.9 vs. 32.1 +/- 1.4 years, P = 0.04). The fasting plasma glucose levels were significantly higher in the post-GDM group than in the control group (4.9 +/- 0.1 vs. 4.4 +/- 0.1 mmol/l, respectively, P < 0.001) and remained higher at each of the subsequent determinations during the oral glucose tolerance test, although none had a result indicative of either diabetes or impaired glucose tolerance.(ABSTRACT TRUNCATED AT 250 WORDS)     

Predictable value of fasting blood glucose level for the incidence of non-insulin-dependent diabetes mellitus]

In order to investigate the predictable value of fasting blood glucose (FBG) level for the incidence of non-insulin-dependent diabetes mellitus (NIDDM), 638 nondiabetic subjects who were investigated in 1986 (including 341 subjects with normal glucose tolerance and 297 subjects with impaired glucose tolerance) were reexamined in 1992. The results showed that the 6-year-incidence of NIDDM was significantly increased with rising of baseline FBG level. After adjusting for age, sex and body mass index (BMI), proportional hazard regression analysis showed that FBG level in impaired glucose tolerance group was positively associated with the development of NIDDM (P = 0.0001). Subjects with mean FBG level of 5.19 mmol/L had a higher risk of developing NIDDM than subjects with mean FBG level of 4.61 mmol/L (RR 2.1, 95% CI 1.19-3.74, P = 0.01). The risk ratio of NIDDM was further increased in the group with mean FBG level of 6.l5 mmol/L (RR = 2.9, 95% CI 1.79-4.59, P = 0.0001). The result indicates that FBG level is an independent risk factor for the development of NIDDM.     

Low birth weight is associated with non-insulin-dependent diabetes mellitus in discordant monozygotic and dizygotic twins

Previous studies have demonstrated an association between low weight at birth and risk of later development of non-insulin dependent diabetes mellitus (NIDDM). It is unknown whether this association may be due to an impact of intrauterine malnutrition per se, or whether it may be due to a coincidence between the putative "NIDDM susceptibility genotype" and a genetically determined low weight at birth. We traced original midwife birthweight record determinations in a group of monozygotic (n = 14 pairs) and dizygotic (n = 14 pairs) twins who phenotypically appeared discordant for NIDDM at a mean age of 67 and 64 years respectively. Birthweights were lower in the NIDDM twins compared with both their identical and non-identical non-diabetic co-twins respectively (p < 0.02 both). Using a similar approach in twin pairs discordant for impaired glucose tolerance (IGT) per se, no significantly decreased birthweight was detected in the IGT twins compared with their non-diabetic co-twins. However, when a larger group of twins with different glucose tolerances were considered, birthweights were lower in twins with abnormal glucose tolerance including both NIDDM and IGT. Furthermore, the twins with the lowest birthweights among the two co-twins had the highest plasma glucose concentrations 120 min after the 75 g oral glucose load (n = 86 pairs, p = 0.02). The study supports the hypothesis that low birthweight and a non-genetically determined intrauterine component such af malnutrition may play a role for the development of NIDDM in twins.     

The potential for lifestyle change to influence the progression of impaired glucose tolerance to non-insulin-dependent diabetes mellitus

Impaired glucose tolerance (IGT) is well recognized as a risk factor for the development of non-insulin-dependent diabetes mellitus (NIDDM). Detecting IGT offers a unique opportunity for targeting intervention to reduce the incidence of NIDDM. This article reviews current evidence for the efficacy of lifestyle intervention programmes involving people with IGT.     

The effect of acarbose on insulin sensitivity in subjects with impaired glucose tolerance

OBJECTIVE: To study the effect of acarbose, an alpha-glucosidase inhibitor, on postprandial plasma glucose and insulin and insulin sensitivity in subjects with impaired glucose tolerance (IGT). RESEARCH DESIGN AND METHODS: Subjects with IGT were randomly treated in a double-blind fashion with placebo (n = 10) or acarbose (n = 8) at 100 mg t.i.d. for 4 months. All subjects were submitted before randomization and at the end of the study to a standardized breakfast and a 12-h daytime plasma glucose and plasma insulin profile, and insulin sensitivity was measured as steady-state plasma glucose (SSPG) using the insulin suppression test. RESULTS: While placebo had no effect on postprandial plasma glucose and plasma insulin incremental area under the curve (AUC) (3.03 +/- 0.5 vs. 3.76 +/- 0.6 mmol.h-1.l-1, P = NS; 1,488 +/- 229 vs. 1,609 +/- 253 pmol.h-1.l-1, P = NS), acarbose resulted in a significant reduction for both glucose (1.44 +/- 0.3 vs. 4.45 +/- 0.9 mmol.h-1.l-1, P = 0.002) and insulin (626.7 +/- 104.3 vs. 1,338.3 +/- 220.5 pmol.h-1.l-1, P = 0.003). The reduction in 12-h plasma glucose and insulin AUC on acarbose (11.2 +/- 2.1 mmol.h-1.l-1 and 7.5 +/- 0.7 nmol.h-1.l-1) was significantly greater than that on placebo (4.0 +/- 1.6 mmol.h-1.l-1 and 0.8 +/- 0.4 nmol.h-1.l-1) (P = 0.014 and 0.041). While SSPG was not affected by placebo (13.9 +/- 0.4 vs. 13.8 +/- 0.3 mmol/l; P = NS), it was significantly improved by acarbose (10.9 +/- 1.4 vs. 13.1 +/- 1.5 mmol/l, P < 0.004) and was also significantly different from placebo at 4 months (P < 0.02). CONCLUSIONS: It is concluded that in subjects with IGT, acarbose treatment decreases postprandial plasma glucose and insulin and improves insulin sensitivity. Acarbose may therefore be potentially useful to prevent the progression of IGT to NIDDM.     

Risk factors for the development of NIDDM in Yonchon County, Korea

OBJECTIVE: To determine the risk factors for the development of NIDDM in Yonchon County of Korea. RESEARCH DESIGN AND METHODS: We studied 1,193 Korean nondiabetic subjects at baseline who participated in a 2-year follow-up study on diabetes in Yonchon County. A 75-g oral glucose tolerance test was performed 2 years after the baseline examination. Age, sex, and anthropometric and metabolic characteristics at baseline were analyzed simultaneously as potential predictors of conversion to NIDDM. We also designed a nested case-control study to determine the role of hyperinsulinemia and/or hyperproinsulinemia in the conversion to NIDDM in patients with newly developed diabetes and control subjects matched for age, sex, BMI, and waist-to-hip-ratio. RESULTS: At 2 years, 67 subjects developed diabetes, as defined by World Health Organization criteria. The age-adjusted incidence was significantly higher in men (6.4%) than in women (3.0%), and the incidence increased as age increased in both sexes. Multiple logistic regression analysis revealed age, male sex, and fasting and 2-h glucose levels to be significant risk factors for the development of NIDDM, whereas waist-to-hip ratio and BMI were not. In a nested case-control study, baseline proinsulin but not insulin levels were significantly higher in subjects who progressed to NIDDM than in those who did not. CONCLUSIONS: In the Korean population, beta-cell dysfunction, as measured by high proinsulin levels, seems to be associated with subsequent development of NIDDM, whereas regional and general obesity and fasting insulin levels, which may be a surrogate for insulin resistance, were not.     

Cloning and functional expression of a human liver organic cation transporter

OBJECTIVE: The triglyceride-lowering effects of omega-3 fats and HDL cholesterol-raising effects of exercise may be appropriate management for dyslipidemia in NIDDM. However, fish oil may impair glycemic control in NIDDM. The present study examined the effects of moderate aerobic exercise and the incorporation of fish into a low-fat (30% total energy) diet on serum lipids and glycemic control in dyslipidemic NIDDM patients. RESEARCH DESIGN AND METHODS: In a controlled, 8-week intervention, 55 sedentary NIDDM subjects with serum triglycerides > 1.8 mmol/l and/or HDL cholesterol < 1.0 mmol/l were randomly assigned to a low-fat diet (30% daily energy intake) with or without one fish meal daily (3.6 g omega-3/day) and further randomized to a moderate (55-65% VO2max) or light (heart rate < 100 bpm) exercise program. An oral glucose tolerance test (75 g), fasting serum glucose, insulin, lipids, and GHb were measured before and after intervention. Self-monitoring of blood glucose was performed throughout. RESULTS: In the 49 subjects who completed the study, moderate exercise improved aerobic fitness (VO2max) by 12% (from 1.87 to 2.07 l/min, P = 0.0001). Fish consumption reduced triglycerides (0.80 mmol/l, P = 0.03) and HDL3 cholesterol (0.05 mmol/l, P = 0.02) and increased HDL2 cholesterol (0.06 mmol/l, P = 0.01). After adjustment for age, sex, and changes in body weight, fish diets were associated with increases in GHb (0.50%, P = 0.05) and self-monitored glucose (0.57 mmol/l, P = 0.0002), which were prevented by moderate exercise. CONCLUSIONS: A reduced fat diet incorporating one daily fish meal reduces serum triglycerides and increases HDL2 cholesterol in dyslipidemic NIDDM patients. Associated deterioration in glycemic control can be prevented by a concomitant program of moderate exercise.     

Beta-cell dysfunction in first-degree relatives of patients with non-insulin-dependent diabetes mellitus

To analyse the relationship between age, glucose tolerance, beta-cell function, and insulin sensitivity in preclinical states of non-insulin-dependent (Type 2) diabetes mellitus (NIDDM), we have done a cross-sectional, age-stratified analysis of 86 non-diabetic first-degree relatives of NIDDM patients and 49 controls with similar age, sex, and BMI. A 5 mg kg ideal body weight-1 min-1 for 60 min of continuous infusion of glucose with model assessment (CIGMA) of serum glucose and C-peptide values at the end of the infusion was used to determine glucose tolerance and beta-cell function. Insulin sensitivity was estimated by modelling basal serum glucose and insulin values. Relatives and controls were divided into tertiles on the basis of age. Relatives had higher basal (5.3 vs 5 mmol l-1, p = 0.02) and achieved serum glucose (9.1 vs 8.4 mmol l-1, p = 0.01), lower beta-cell function (128 vs 145%, p = 0.007), and lower insulin sensitivity (37 vs 43%, p = 0.002). Beta-cell function declined with age in relatives (from 139% in young subjects to 134% in intermediate subjects and to 111% in older subjects, p = 0.002) and this decline was associated with an increase in basal serum glucose (from 5.1 to 5.3 and to 5.7 mmol l-1, p = 0.000) and achieved glucose (from 8.3 to 9.1 and to 9.3 mmol l-1, p = 0.038), without significant changes in insulin sensitivity. These trends were observed even after the exclusion of subjects with mild glucose intolerance. We conclude that both beta-cell dysfunction and insulin resistance are present in first-degree relatives of NIDDM. The progression of beta-cell dysfunction and glucose intolerance with age suggests that beta-cell dysfunction is the key factor in the apparition and progression of the disease.     

A follow-up program for women with previous gestational diabetes mellitus

OBJECTIVE: To analyse the patterns of attendance in a gestational diabetes mellitus (GDM) follow-up program for detection of impaired glucose tolerance and diabetes mellitus. DESIGN: Retrospective cohort study using computerised data from the GDM follow-up program. PARTICIPANTS AND SETTING: All women with GDM who delivered at the Mercy Hospital for Women in Victoria between 1 January 1981 and 31 December 1995. OUTCOME MEASURES: Enrollment and maintenance in the follow-up program. Predictors of attendance analysed were attendance for the postnatal oral glucose tolerance test (OGTT), severity of GDM, insulin requirement in pregnancy, age at index pregnancy, country of birth, patient booking status and year of index pregnancy. RESULTS: There were 3524 women with GDM delivered during the study period. Attendance for postnatal OGTT was 71% and increased from 43.7% to 69.5% to 84.4% during the three five-year periods of the study (P < 0.00001). Entry into the follow-up program was 58% (1743 of 2986 eligible). A further 538 women (15.3%) were awaiting the postnatal OGTT or first follow-up OGTT. By December 1995, 45% of women who had entered the program had been lost to follow-up. Enrollment in the follow-up program was significantly predicted by insulin requirement in pregnancy (odds ratio [OR], 2.22; 95% confidence interval [95% CI], 1.57-3.13), attendance for postnatal OGTT (OR, 1.94; 95% CI, 1.64-2.29), private patient status (OR, 1.31; 95% CI, 1.12-1.54), severity of GDM (OR, 1.50; 95% CI, 1.24-1.82) and age 30 years or more (OR, 1.37; 95% CI, 1.17-1.60). Maintenance in the follow-up program was significantly associated with attendance for postnatal OGTT (OR, 2.67; 95% CI, 2.19-3.24), insulin requirement in pregnancy (OR, 2.56; 95% CI, 1.87-3.50), age 30 years or more (OR, 1.59; 95% CI, 1.34-1.88) and severity of GDM (OR, 1.55; 95% CI, 1.28-1.89). CONCLUSIONS: There are major difficulties with both recruiting women with GDM into a follow-up program and ensuring their continued attendance. However, a postnatal OGTT and consultation is the most important remediable factor for continuation in a follow-up program. The dedication of the follow-up team administrators rather than the clinical variables of the patients was probably the main determinant of compliance with the follow-up program.     

NIDDM genes in mice: deleterious synergism by both parental genomes contributes to diabetogenic thresholds

We used mouse genetics to model how polygenic thresholds for the transition from impaired glucose tolerance (IGT) to NIDDM are reached. NON/Lt and NZO/Hl are inbred mouse strains selected for IGT and polygenic obesity, respectively. Their F1 male progeny consistently developed NIDDM. Genetic analysis of F2 males from both cross directions identified an NON-derived diabetogenic locus, Nidd 1, on chromosome (Chr) 4 near the leptin receptor. This locus was associated with reduced plasma insulin, increased non-fasted blood glucose, and lower body weight. Another NON-derived diabetogenic locus on Chr 18 (Nidd2) that controls blood glucose was identified. An NZO-derived diabetogenic region on Chr 11 (Nidd3), possibly comprising two separate loci, reduced ability to sustain elevated plasma insulin and significantly reduced weight gain over time. Thus, the diabetogenic synergism between genetic loci from strains separately exhibiting subthreshold defects perturbing glucose homeostasis underscores the likely complexity of the inheritance of obesity-associated forms of NIDDM in humans.