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Background: Age is associated with both impaired glucose and insulin metabolism. To what extent the age-related changes in insulin resistance (IR) and beta-cell function contribute to the increase in prevalence of impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) is less known, and this is investigated in this study., Methods: This study included 6610 men and 7664 women of different ethnic groups aged 30-69 years. IR and beta-cell function were examined by the homeostasis model assessment of insulin resistance (HOMA-IR) and homeostasis model assessment of beta-cell function (HOMA-B). Odds ratios (ORs) and 95% confidence intervals (95% CIs) were estimated using logistic regression analysis adjusting for body mass index and study., Results: In Chinese men, the ORs (95% CIs) for IFG were 2.69 (1.70, 4.26), 2.51 (1.49, 4.21) and 2.89 (1.68, 4.97), respectively, in age groups of 40-49, 50-59 and 60-69 years compared with 30-39 years (p < 0.001 for trend); the corresponding figures for IGT were 1.73 (1.25, 2.38), 2.54 (1.78, 3.63) and 3.57 (2.46, 5.19) (p < 0.001 for trend). Similar trends for IGT were observed also in Chinese women and other ethnic groups, but not for IFG in Mauritius Indian and Creole men. Adjustment for HOMA-IR and HOMA-B reduced the ORs in all age groups of all ethnicities for both IFG and IGT, but the risk gradient between age groups remained particularly for the IGT., Conclusions: The age-related increase in glucose intolerance may not be fully explained by the defect in HOMA-IR and HOMA-B. As HOMA-IR and HOMA-B are only surrogate measures of insulin sensitivity and insulin secretion, the results need to be further investigated.

Elevated 2-h plasma glucose concentration (2hPG) from an oral glucose tolerance (OGTT) test more strongly predicts risk of subsequent cardiovascular disease than fasting plasma glucose (FPG), but the association between these glucose measurements and hypertension risk is less clear. We examined the association between 2hPG, FPG and risk of hypertension. We conducted a prospective observational study (The Australian Diabetes, Obesity and Lifestyle Study-AusDiab) among 4413 Australian residents who attended a baseline (1999-2000) and follow-up (2004-2005) examinations. Measurements included blood pressure (mean of two readings), 75 g OGTT, fasting insulin, anthropometrics, dietary and alcohol intake, medical history and physical activity. Hypertension was defined as a systolic blood pressure (SBP)> or =140 or a diastolic blood pressure (DBP)> or =90 mm Hg or treatment with medication for hypertension. HOMA-S was calculated as a measure of insulin sensitivity using the HOMA2 calculator. Hypertension developed in 14% of the 4306 subjects available for this analysis. Higher 2hPG was significantly related to greater risk of hypertension after adjustment for age, gender, FPG, BMI (baseline and difference), waist circumference (baseline and difference), education, exercise, alcohol intake, baseline SBP and smoking (OR (95% CI) 1.12 (1.01 to 1.23)), but no significant association was seen between FPG and hypertension in this model (1.02 (0.88-1.19)). Further adjustment for HOMA-S did not change these findings. Higher baseline 2hPG was more strongly associated with an increase in SBP than in DBP over 5 years. We conclude that higher 2hPG predicted future hypertension occurrence in this population.

Objective: To compare the American Diabetes Association (ADA) fasting glucose and the World Health Organization (WHO) oral glucose tolerance test (OGTT) criteria for diagnosing diabetes and detecting people at increased risk for cardiovascular disease (CVD)., Research Design and Methods: Study subjects were 596 Japanese-Americans. Fasting insulin, lipids, and C-peptide levels; systolic and diastolic blood pressures (BPs); BMI (kg/m2); and total and intra-abdominal body fat distribution by computed tomography (CT) were measured. Study subjects were categorized by ADA criteria as having normal fasting glucose (NFG), impaired fasting glucose (IFG), and diabetic fasting glucose and by WHO criteria for a 75-g OGTT as having normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and diabetic glucose tolerance (DGT)., Results: Of 503 patients with NFG, 176 had IGT and 20 had DGT These patients had worse CVD risk factors than those with NGT . The mean values for NGT, IGT, and DGT, respectively, and analysis of covariance P values, adjusted for age and sex, are as follows; intra-abdominal fat area by CT 69.7, 95.0, and 101.1 cm2 (P < 0.0001); total CT fat area 437.7, 523.3, and 489.8 cm2 (P < 0.0001); fasting triglycerides 1.40, 1.77, and 1.74 mmol/l (P = 0.002); fasting HDL cholesterol 1.56, 1.50, and 1.49 mmol/l (P = 0.02); C-peptide 0.80, 0.90, 0.95 nmol/l (P = 0.002); systolic BP 124.9, 132.4, and 136.9 mmHg (P = 0.0035); diastolic BP 74.8, 77.7, and 78.2 mmHg (P = 0.01)., Conclusions: NFG patients who had IGT or DGT had more intra-abdominal fat and total adiposity; higher insulin, C-peptide, and triglyceride levels; lower HDL cholesterol levels; and higher BPs than those with NGT. Classification by fasting glucose misses many Japanese-Americans with abnormal glucose tolerance and less favorable cardiovascular risk profiles.

Objective: For epidemiological purposes, it has now been recommended that a fasting plasma glucose value of 7.0 mmol/l can be used to diagnose diabetes, instead of a 2-h value of 11.1 mmol/l. This study assesses the impact of making this change on the prevalence of diabetes and on the phenotype of individuals identified., Research Design and Methods: Data were collated from nine population based southern hemisphere studies in which a 75-g oral glucose tolerance test was performed. Comparisons were made between the prevalence derived from fasting values only and the prevalence derived from 2-h values only. Cardiovascular risk was assessed in all individuals., Results: There were 20,624 subjects in the nine surveys of whom 1,036 had previously diagnosed diabetes and 1,714 had newly diagnosed diabetes, according to either fasting or 2-h glucose. The differences in prevalence within each population resulting from changing the diagnostic criteria ranged from +30 to -19% (relative difference) and +4.1 percentage points to -2.8 percentage points (absolute difference). BMI was the most important determinant of disagreement in classification. A total of 31% of those individuals who were diabetic on the fasting value were not diabetic on the 2-h value, and 32% of those with diabetes on the 2-h value were not diabetic on the fasting value. Apart from obesity, there were no differences in cardiovascular risk between those identified by the fasting and the 2-h values., Conclusions: Changing the diagnostic criteria is likely to have variable and sometimes quite large effects on the prevalence of diabetes in different populations. Furthermore, the fasting criterion identifies different people as being diabetic than those identified by the 2-h criterion.

Islet amyloid is a characteristic feature of type 2 diabetes. Its major component is the normal beta-cell secretory product amylin, or islet amyloid polypeptide (IAPP). To determine whether increased or disproportionate release of amylin may explain the propensity for amyloid deposition in type 2 diabetes, we measured plasma amylin-like immunoreactivity (ALI) and immunoreactive insulin (IRI) release in response to an oral glucose load in 94 Japanese-American subjects with normal glucose tolerance (NGT; n=56), impaired glucose tolerance (IGT; n=10), and type 2 diabetes (n=28) as defined by World Health Organization criteria. The incremental increase in ALI, IRI, and glucose (G) at 30 min after oral glucose ingestion was used to calculate deltaALI/deltaG and deltaIRI/deltaG as measures of beta-cell function. Overall glucose metabolism was assessed as the incremental glucose area (glucose AUC) during the 2 h of the oral glucose tolerance test. As expected, plasma glucose concentrations at both fasting (NGT, 5.0+/-0.4; IGT, 5.5+/-0.1; type 2 diabetes, 6.2+/-0.3 mmol/l; P < 0.0001) and 2 h (NGT, 6.7+/-0.1; IGT, 9.4+/-0.3; type 2 diabetes, 13.2 +/-0.5 mmol/l; P < 0.0001) were elevated in individuals with IGT and type 2 diabetes. In response to glucose ingestion, plasma IRI and ALI increased in all subjects, but these increments were lower in individuals with reduced glucose tolerance, as reflected in the deltaIRI/deltaG (NGT, 119+/-10.3; IGT, 60.7+/-7.1; type 2 diabetes, 49.7 +/-5.4 pmol/l; P < 0.0001) and deltaALI/deltaG (NGT, 2.6+/-0.2; IGT, 1.8+/-0.3; type 2 diabetes, 1.2+/-0.1 pmol/l; P < 0.0001). Moreover, these reductions in the 30-min incremental ALI and IRI responses were proportionate such that the molar ratio of ALI to IRI was not different among the three groups (NGT, 2.6+/-0.2; IGT, 2.9 +/-0.3; type 2 diabetes, 2.9+/-0.3%; NS). Further, the relationship between beta-cell function, measured as either deltaIRI/deltaG or deltaALI/deltaG, and glucose metabolism, assessed as glucose AUC, was nonlinear and inverse in nature, with r2 values of 0.38 (P < 0.0001) and 0.33 (P < 0.0001), respectively. We conclude that the reduced beta-cell function of IGT and type 2 diabetes includes proportionate reductions in both IRI and ALI release. Thus, it is unlikely that the development of islet amyloid in type 2 diabetes is the result of increased release of ALI.

Disproportionate hyperproinsulinaemia is a manifestation of the beta-cell dysfunction observed in NIDDM. However, it is unclear when this abnormality develops and whether it predicts the development of the disease. To examine whether changes in proinsulin levels predict the development of NIDDM, baseline measurements of proinsulin and immunoreactive insulin levels were made in 87 second-generation Japanese-American men, a population at high risk for the subsequent development of NIDDM. Subjects were categorized at baseline using WHO criteria as having normal glucose tolerance (NGT; n = 49) or impaired glucose tolerance (IGT; n = 38). After a 5-year follow-up period, subjects were recategorized as having NGT, IGT or NIDDM using the same criteria. During follow-up, 16 subjects developed NIDDM while 71 were NGT or IGT. At baseline, individuals who subsequently developed NIDDM were more obese as measured by intra-abdominal fat area on computed tomography (p = 0.046), had higher fasting glucose (p = 0.0042), 2-h glucose (p = 0.0002), fasting C-peptide (p = 0.0011), fasting proinsulin levels (p = 0.0033), and had disproportionate hyperproinsulinaemia (p = 0.056) when compared to those who remained NGT or IGT after 5 years of follow-up. These findings suggest that alterations in proinsulin levels may also predict the subsequent development of NIDDM.

Glucose disposal occurs by both insulin-independent and insulin-dependent mechanisms, the latter being determined by the interaction of insulin sensitivity and insulin secretion. To determine the role of insulin-independent and insulin-dependent factors in glucose tolerance, we performed intravenous glucose tolerance tests on 93 young healthy subjects (55 male, 38 female; 18-44 years of age; body mass index, 19.5-52.2 kg/m2). From these tests, we determined glucose tolerance as the glucose disappearance constant (Kg), calculated beta-cell function as the incremental insulin response to glucose for 19 min after an intravenous glucose bolus (IIR0-19), and derived an insulin sensitivity index (SI) and glucose effectiveness at basal insulin (SG) using the minimal model of glucose kinetics. To eliminate the effect of basal insulin on SG and estimate insulin-independent glucose uptake, we calculated glucose effectiveness at zero insulin (GEZI = SG - [SI x basal insulin]). Insulin-dependent glucose uptake was estimated as SI x IIR0-19, because the relationship between SI and beta-cell function has been shown to be hyperbolic. Using linear regression to determine the influence of these factors on glucose tolerance, we found that GEZI was significantly related to Kg (r = 0.70; P < 0.0001), suggesting a major contribution of insulin-independent glucose uptake to glucose disappearance. As expected, SI x IIR0-19 also correlated well with Kg (r = 0.74; P < 0.0001), confirming the importance of insulin-dependent glucose uptake to glucose tolerance. Although IIR0-19 alone correlated with Kg (r = 0.35; P = 0.0005), SI did not (r = 0.18; P > 0.08).(ABSTRACT TRUNCATED AT 250 WORDS)

Objective: To explore the associations between blood pressure and both fasting insulin and C-peptide levels., Research Design and Methods: A cross-sectional analysis was conducted of 895 normoglycemic members of a bi-ethnic community in Colorado who were selected from a control group recruited for a geographically based study of diabetes mellitus prevalence and risk factors. All subjects included in this study had normal glucose tolerance as judged by a 75-g oral glucose tolerance test interpreted using World Health Organization criteria. None of the subjects were taking antihypertensive medication. Multiple linear regression analysis was used to examine relationships between fasting insulin and C-peptide levels and blood pressure., Results: Among all subjects, diastolic blood pressure was found to significantly increase with increasing levels of both hormones (insulin coefficient = 0.197, P = 0.013; C-peptide coefficient = 0.0436, P = 0.004), whereas systolic blood pressure was significantly related to fasting C-peptide level (coefficient = 0.0295, P = 0.050). These relationships were similar in magnitude for both Hispanic and non-Hispanic white subjects, but were diminished among women and subjects with a higher body mass index., Conclusions: Higher fasting insulin and C-peptide levels are associated with higher blood pressure, but these relationships are modified by sex and degree of obesity.

Objective: To ascertain whether childbearing would decrease oral glucose-stimulated insulin and C-peptide levels and increase the risk of NIDDM and impaired glucose tolerance in a population of Hispanic and non-Hispanic white women residing in the San Luis Valley of Colorado. Several investigators have related childbearing to subsequent abnormal glucose tolerance., Research Design and Methods: In a population-based case-control epidemiological study, diabetic patients 20-74 yr of age (n = 196) and randomly sampled control women subjects (n = 735) underwent a glucose tolerance test, a physical examination, and an in-person standardized interview. The relations between the live-birth number and fasting and oral glucose stimulated glucose, insulin and C-peptide concentrations, and NIDDM and impaired glucose tolerance were estimated using linear or logistic regression to adjust for extraneous variables., Results: In women selected as control subjects, the live-birth number was related to a significant decrease in the sum of 1- and 2-h C-peptide concentrations (coefficient = -0.077, P < 0.001) and the logarithm of the sum of 1- and 2-h insulin concentrations (coefficient = -0.014, P = 0.02). After adjustment for subscapular skin-fold thickness, the relative odds of NIDDM for the live-birth number, which was small and of borderline significance, diminished (odds ratio = 1.04 for one birth, P = 0.18). Findings were similar for impaired glucose tolerance., Conclusions: Childbearing was related to lower C-peptide and insulin levels in Hispanic and non-Hispanic women of the San Luis Valley. It had little apparent effect on later risk of NIDDM or impaired glucose tolerance.

Objective: Investigate the Accu-Chek II and visual Chemstrip bG methods for non-insulin dependent diabetes mellitus (NIDDM) screening under field conditions with the aid of local providers., Methods: Compare simultaneous random Chemstrip bG, Accu-Chek II and plasma glucose levels using a 6.7 mM cut-off, followed by a 75 gram 2 hour oral glucose tolerance test while screening 1124 people in 15 Alaskan villages with the aid of local personnel during winter field conditions., Results: The Accu-Chek II and visual Chemstrip bG methods detected 92% and 96%, respectively, of those newly diagnosed with NIDDM whose plasma screen was > or = 6.7 mM. The Accu-Chek II provided correlations of 0.774, 0.850, 0.923, and 0.946 with random, fasting, 1 and 2 hour plasma glucose. The mean Accu-Chek II, Chemstrip bG and plasma levels at which NIDDM was diagnosed were not statistically different. Receiver operator characteristic (ROC) curve analysis revealed optimum screening cut-off values for subsequent new diagnosis of NIDDM to be 8.3, 7.7, and 8.0 mM for visual, Accu-Chek II and hexokinase methods (p = NS)., Conclusion: The Accu-Chek II and Chemstrip bG provided accurate glucose data in random NIDDM screening under field conditions with multiple local providers.

The goal of this study was to estimate the effects of childbearing on subsequent glucose tolerance and non-insulin-dependent diabetes mellitus (NIDDM) prevalence. A sample of subjects from 64 different locations in the United States were recruited for inclusion in the Second National Health and Nutrition Examination Survey. A complex survey design was used to select a probability sample of subjects from each location. A total of 4577 women were recruited, of whom 3057 underwent clinical and laboratory evaluation for the presence of diabetes mellitus. Women were classified as to their glucose tolerance based on the results of an oral glucose tolerance test or previous physician diagnosis of diabetes mellitus combined with current use of hypoglycemic medication. Childbearing was defined as number of live births experienced by each woman at the time of the interview. Fasting plasma glucose increased linearly with increasing number of live births (coefficient 0.009, 95% confidence interval [CI] 0.006-0.012), as did the 2-h value (coefficient 0.015, 95% CI 0.009-0.021). Adjustment for age, body mass index (BMI), education, and income substantially reduced the magnitude of the association between childbearing and either plasma glucose measurement. When the prevalence of NIDDM in relation to childbearing was examined with logistic regression analysis, a significant linear increase in diabetes prevalence was seen with increasing number of live births (relative prevalence of NIDDM, 1 birth vs. 0 = 1.73, 95% CI 1.39-2.15), but adjustment for age, BMI, education, and income greatly reduced the magnitude of this association (relative prevalence of NIDDM, 1 birth vs. 0 = 1.07, 95% CI 0.98-1.17).(ABSTRACT TRUNCATED AT 250 WORDS)