HbA1c measurement improves the detection of type 2 diabetes in high-risk individuals with nondiagnostic levels of fasting plasma glucose: the Early Diabetes Intervention Program (EDIP)

OBJECTIVE: Whereas new diagnostic criteria based on a fasting plasma glucose (FPG) of > 126 mg/dl (7.8 mmol/l) have improved the detection of diabetes, multiple reports indicate that many people with diabetes diagnosed by 2-h oral glucose tolerance test (OGTT) glucose measurements > or = 11.1 mmol/l (200 mg/dl) would remain undiagnosed based on this FPG criteria. Thus, improved methods to detect diabetes are particularly needed for high-risk individuals. We evaluated whether the combination of FPG and HbA1c measurements enhanced detection of diabetes in those individuals at risk for diabetes with nondiagnostic or minimally elevated FPG. RESEARCH DESIGN AND METHODS: We analyzed FPG, OGTT, and HbA1c data from 244 subjects screened for participation in the Early Diabetes Intervention Program (EDIP). RESULTS: Of 244 high-risk subjects studied by FPG measurements and OGTT, 24% of the individuals with FPG levels of 5.5-6.0 mmol/l (100-109 mg/dl) had OGTT-diagnosed diabetes, and nearly 50% of the individuals with FPG levels of 6.1-6.9 mmol/l (110-125 mg/dl) had OGTT-diagnosed diabetes. In the subjects with OGTT-diagnosed diabetes and FPG levels between 5.5 and 8.0 mmol/l, detection of an elevated HbA1c (>6.1% or mean + 2 SDs) led to a substantial improvement in diagnostic sensitivity over the FPG threshold of 7.0 mmol/l (61 vs. 45%, respectively, P = 0.002). Concordant FPG levels > or = 7.0 mmol/l (currently recommended for diagnosis) occurred in only 19% of our cohort with type 2 diabetes. CONCLUSIONS: Diagnostic criteria based on FPG criteria are relatively insensitive in the detection of early type 2 diabetes in at-risk subjects. HbA1c measurement improves the sensitivity of screening in high-risk individuals.     

Macrovascular risk and diagnostic criteria for type 2 diabetes: implications for the use of FPG and HbA(1c) for cost-effective screening

OBJECTIVE: The use of fasting plasma glucose (FPG) level > or =7.0 mmol/l leads to underdiagnosis of type 2 diabetes compared with the oral glucose tolerance test (OGTT). The OGTT is of limited use for population screening. Most of the increase in cardiovascular risk in relation to increasing blood glucose occurs before the threshold at which the diagnosis of type 2 diabetes is made. The aim of this study was to evaluate the use of HbA(1c) and FPG as predictors of type 2 diabetes and cardiovascular risk and, accordingly, to develop a rational approach to screening for abnormalities of glucose tolerance. RESEARCH DESIGN AND METHODS: OGTT and measurement of HbA(1c) and FPG levels were performed in 505 subjects screened for type 2 diabetes. Anthropomorphic measurements were obtained. A cardiovascular risk factor questionnaire was completed. RESULTS: The subjects were aged 19-88 years (mean 53.8). The incidence of type 2 diabetes was 10.4% based on the OGTT and 4% based on an FPG level > or =7.0 mmol/l. Using high-performance liquid chromatography (HPLC), HbA(1c) of <4.7 and > or =6.2% predicted with certainty the absence or presence of type 2 diabetes as defined by the OGTT. The corresponding cutoffs were <5.0 and > or =6.8% for HbA(1c) (DCA2000 HPLC device; Bayer Diagnostics, Mulgrave, Australia) and <4.7 and > or =6.4 mmol/l for FPG. However, 75-85% of subjects in each case had intermediate values, which were therefore nondiagnostic. Cardiovascular risk increased at least 2.2 times at an HbA(1c) level > or =6.2% (by HPLC), 1.8-2.2 times at an HbA(1c) level of 5.6-6.1% (by HPLC), 2 times at an FPG level > or =6.4 mmol/l, and 1.7-1.9 times at an FPG level of 5.6-6.3 mmol/l. CONCLUSIONS: Measurement of FPG and HbA(1c) levels will diagnose or exclude type 2 diabetes with certainty in a minority (15%) of people. There is a continuous relationship between FPG and HbA(1c) and cardiovascular risk. Accordingly, we propose that there is a rational basis for using either FPG and HbA(1c) for purposes of screening and assigning risk. Individuals with an HbA(1c) level of 5.6-6.1% and an FPG level of 5.6-6.3 mmol/l are at greatest risk for cardiovascular disease and should be targeted for further evaluation. An algorithm outlining a cost-effective approach is presented.     

Reproducibility of the diagnosis of diabetes over a 30-month follow-up: the Paris Prospective Study.

OBJECTIVE: To describe the change in diabetic status over 30 months. RESEARCH DESIGN AND METHODS: Cohort study of 5,400 Caucasian men from the Paris Prospective Study, aged 44-55 years, who were not known as having diabetes at baseline. Oral glucose tolerance tests were performed at baseline and after 30 months. RESULTS: At baseline, diabetes was diagnosed in 2.9% of the men by fasting plasma glucose (FPG) > or =7.0 mmol/l and in 0.9% by isolated postchallenge hyperglycemia (IPH) (FPG <7.0 mmol/l and 2-h plasma glucose concentration > or =11.1 mmol/l), i.e., one in four of all men with newly diagnosed diabetes. Thirty months later, 42% of the men with diabetes diagnosed by FPG reverted to nondiabetic status, compared with 72% of those with diabetes diagnosed by IPH (P < 0.0001). For the men with diabetes diagnosed by FPG at baseline, diabetes had been diagnosed by a physician at 30 months in 11.5%, in contrast to only 3.9% of those with diabetes diagnosed by IPH (P < 0.05). For the 51 men with diabetes diagnosed by IPH at baseline, those who reverted to nondiabetic status had a lower frequency of family history of diabetes (P < 0.1), a higher mean corpuscular volume (P < 0.08), and a significantly higher total cholesterol concentration (P < 0.006) at baseline; in contrast, for the 156 men with diabetes diagnosed by FPG at baseline, the men who reverted to nondiabetic status and those who remained diabetic had similar characteristics. CONCLUSIONS: In this epidemiological study, diabetes diagnosed by one FPG concentration was more stable than diabetes diagnosed by one IPH; in clinical practice, the diagnosis of diabetes requires confirmation of the hyperglycemia.     

From policemen to policies: what is the future for 2-h glucose? The Kelly West Lecture, 2000.

OBJECTIVE: To describe the characteristics and vital prognosis of men with diabetes diagnosed by one fasting plasma glucose (FPG) concentration > or =7.0 mmol/l, with diabetes diagnosed by one isolated postchallenge hyperglycemia (IPH) (FPG <7.0 mmol/l and a 2-h plasma glucose concentration > or =11.1 mmol/l), or with impaired glucose tolerance (IGT). RESEARCH DESIGN AND METHODS: This study involved a cohort of 6,881 Caucasian nondiabetic men from the Paris Prospective Study, aged 44-55 years, who were followed for cause of death for 20 years. RESULTS: Diabetes was diagnosed in 4.3% of the men (1.0% diabetes diagnosed by IPH), and IGT was diagnosed in 9% of the men. At baseline, the men with diabetes diagnosed by IPH had a lower cardiovascular risk profile than those with diabetes diagnosed by FPG, as did the men with IGT and a normal fasting glucose level (<6.1 mmol/l, IGT and normal fasting glucose), compared with men with impaired fasting glucose (6.1-6.9 mmol/l, IGT and impaired fasting glucose [IFG]). At 20 years of follow-up, all-cause and cancer death rates were higher in men with diabetes diagnosed by IPH than in men with diabetes diagnosed by FPG (55 vs. 44%, P < 0.1 and 31 vs. 17%, P < 0.01, respectively) but were not significantly different for coronary causes (6 vs. 11%). Men with IGT and normal fasting glucose also had significantly higher cancer death rates than men with IGT and IFG. CONCLUSIONS: The most likely explanation for the high cancer and low coronary death rates is that men with diabetes diagnosed by IPH consumed alcohol; the men in this study drank 49 g of pure alcohol on average per day, equivalent to 0.6 l of wine. If these results are confirmed by other prospective studies, screening subjects for isolated postchallenge hyperglycemia may not be worthwhile.     

Risk factors for development of pre-diabetic state from normal glucose regulation

As a strategy to prevent the progression of diabetes mellitus, it is important to screen out the subjects who will develop a pre-diabetic state (PDS) in the future. To find out the potential risk factors for PDS, we employed the values of fasting plasma glucose and hemoglobin A1c (HbA1c), which are routinely measured in our health checkup. We selected 3,879 individuals who had normal glucose regulation at both fasting plasma glucose < 6.1 mmol/l and HbA1c < 5.5% in 1997 and investigated whether they would develop PDS in the next 5 years. PDS is defined at fasting plasma glucose >or= 6.1 mmol/l and HbA1c >or= 5.5%. Among 3,879 individuals, 21 developed PDS and 2,128 maintained normal glucose regulation in 2001. The remaining 1,730 subjects fit one of the two criteria for PDS. The parameters measured in 1997, including fasting plasma glucose, HbA1c, triglyceride, alanine aminotransferase, gamma-glutamyltranspeptidas, cholinesterase, uric acid, red blood cells, hemoglobin, percent body fat and diastolic blood pressure, were significantly higher in the individuals who developed PDS than in those who maintained normal glucose regulation. On the other hand, hematocrit was significantly lower in PDS than in normal glucose regulation. Logistic regression analysis identified alanine aminotransferase >or= 40 U/l, triglyceride >or= 1.69 mmol/l, low-density lipoprotein cholesterol >or= 3.62 mmol/l and hematocrit < 38% as valuable factors for predicting the development of PDS. The present study demonstrates that the subjects with high risks for PDS could be identified from several clinical parameters and that they should be encouraged to improve their living habits not to develop diabetes mellitus.     

Postprandial peaks as a risk factor for cardiovascular disease: epidemiological perspectives

A key issue in diabetes care is selecting glucose parameters to monitor and control. The recommendations of the American Diabetes Association for glycaemic control do not address postprandial glucose (PPG), but patients with type 2 diabetes experience wide variations in glucose levels after meals. We have observed a remarkable increase in plasma glucose two hours after breakfast and/or lunch in most non-insulin-treated patients; for up to 40% of them the increase is >40 mg/dl (2.2 mmol/l). As many as 70% of patients with an HbA1c <7% have PPG values >160 mg/dl (8.9 mmol/l) after meals. Fasting plasma glucose (FPG) is a poor indicator of plasma glucose at other times. The coefficient of correlation of FPG with plasma glucose at other times ranges from 0.50-0.70. Nor is the correlation of FPG with HbA1c very strong: in hundreds of determinations of HbA1c and FPG in our patients, the coefficient of correlation was not greater than 0.73. For the same FPG value, HbA1c varied markedly, and vice versa; further, the correlation between PPG and HbA1c was no higher than that between FPG and HbA1c (r = 0.65). Thus, monitoring in type 2 diabetes should include PPG along with FPG and HbA1c. Recent data provide direct and indirect evidence suggesting that PPG is independently related to cardiovascular disease (CVD), and supporting the idea that PPG should be assessed and glucose excursions with meals should be controlled: 1. Studies conducted by other investigators and ourselves in patients with type 2 diabetes have shown that the incidence of CVD is independently related to postprandial or post-OGTT (oral glucose tolerance test) blood glucose at baseline. In addition, data collected in the general population show an association between 2-hour OGTT plasma glucose (a surrogate of PPG) and cardiovascular morbidity and mortality that is independent of FPG. Also, subjects with impaired glucose tolerance (IGT) and isolated post-challenge hyperglycaemia have an increased cardiovascular risk over subjects with normal glucose tolerance (NGT). We found that IGT subjects had a risk of carotid stenosis 3-fold higher than subjects with NGT, even after adjustment for several confounders. Thus, a modest increase in post-OGTT plasma glucose and, by extrapolation, PPG seems to have a major detrimental effect on the arteries. 2. When FPG and/or HbA1c were the targets of glucose control in studies of patients with type 2 diabetes (the UGDP, VACSDM, and UKPDS) the effects on CVD were minimal. However, when the targets of glucose control included PPG (the Kumamoto Study and DIGAMI Study) favorable effects on CVD were observed. 3. There is experimental data suggesting that acute hyperglycaemia can exert deleterious effects on the arterial wall through mechanisms including oxidative stress, endothelial dysfunction, and activation of the coagulation cascade. This evidence prompted the European Diabetes Policy Group to set postprandial targets for blood glucose control: postprandial peaks should not exceed 135 mg/dl (7.5 mmol/ml) to reduce arterial risk and should not exceed 160 mg/dl (8.9 mmol/l) to reduce microvascular risk. Thus, glucose care in diabetes is not only "fasting glucose care" or "HbA1c care" but is also "postprandial glucose care."     

Effect of metformin in pediatric patients with type 2 diabetes: a randomized controlled trial.

OBJECTIVE: Metformin is the most commonly prescribed oral antidiabetic agent in the U.S. for adults with type 2 diabetes. The incidence of type 2 diabetes in children has increased dramatically over the past 10 years, and yet, metformin has never been formally studied in children with type 2 diabetes. RESEARCH DESIGN AND METHODS: This study evaluated the safety and efficacy of metformin at doses up to 1,000 mg twice daily in 82 subjects aged 10-16 years for up to 16 weeks in a randomized double-blind placebo-controlled trial from September 1998 to November 1999. Subjects with type 2 diabetes were enrolled if they had a fasting plasma glucose (FPG) levels > or =7.0 and < or =13.3 mmol/l (> or =126 and < or =240 mg/dl), HbA(1c) > or =7.0%, stimulated C-peptide > or =0.5 nmol/l (> or =1.5 ng/ml), and a BMI > 50th percentile for age. RESULTS: Metformin significantly improved glycemic control. At the last double-blind visit, the adjusted mean change from baseline in FPG was -2.4 mmol/l (-42.9 mg/dl) for metformin compared with +1.2 mmol/l (+21.4 mg/dl) for placebo (P < 0.001). Mean HbA(1c) values, adjusted for baseline levels, were also significantly lower for metformin compared with placebo (7.5 vs. 8.6%, respectively; P < 0.001). Improvement in FPG was seen in both sexes and in all race subgroups. Metformin did not have a negative impact on body weight or lipid profile. Adverse events were similar to those reported in adults treated with metformin. CONCLUSION: Metformin was shown to be safe and effective for treatment of type 2 diabetes in pediatric patients.     

Impaired fasting glucose: how low should it go?

OBJECTIVE: Impaired fasting glucose (IFG) has been recently introduced as a stage of abnormal carbohydrate metabolism, but the evidence on which its glucose limits (fasting plasma glucose [FPG] 6.1-6.9 mmol/l) are based is not strong. The aim of this study was to determine if 6.1 mmol/l represents a clear cutoff in terms of the risk of future diabetes and in terms of elevated cardiovascular risk factor levels, and to examine the use of other lower limits of IFG. RESEARCH DESIGN AND METHODS: A population-based survey of the island of Mauritius was undertaken in 1987, with a follow-up survey 5 years later. On both occasions, an oral glucose tolerance test was performed and cardiovascular risk factors were measured. RESULTS: Data were available from 4,721 nondiabetic people at baseline, and from 3,542 at follow-up. At baseline, blood pressure, lipids, and obesity increased in a linear fashion with increasing FPG, with no evidence of a threshold effect. The risk of developing hypertension at follow-up was greater for those people with baseline FPG > or =6.1 mmol/l (P<0.001). The risk of developing diabetes at follow-up increased with increasing baseline FPG, but there was little evidence of a threshold near 6.1 mmol/l. CONCLUSIONS: Cardiovascular risk and risk of future diabetes increase continually with increasing FPG, and there is no threshold value on which to base a definition of IFG. If a lower limit of approximately 5.8 mmol/l is used, the category defines a group more similar to the group with impaired glucose tolerance, with regard to total prevalence and the risk of subsequent diabetes.     

Nateglinide alone and in combination with metformin improves glycemic control by reducing mealtime glucose levels in type 2 diabetes

OBJECTIVE: To evaluate the efficacy and tolerability of nateglinide and metformin alone and in combination in type 2 diabetic patients inadequately controlled by diet, focusing on changes in HbA1c, fasting plasma glucose (FPG), and mealtime glucose excursions. RESEARCH DESIGN AND METHODS: In this randomized double-blind study, patients with an HbA1c level between 6.8 and 11.0% during a 4-week placebo run-in received 24 weeks' treatment with 120 mg nateglinide before meals (n = 179), 500 mg metformin three times a day (n = 178), combination therapy (n = 172), or placebo (n = 172). HbA1c and FPG were evaluated regularly, and plasma glucose levels were determined after Sustacal challenge at weeks 0, 12, and 24. Hypoglycemia and other adverse events were recorded. RESULTS: At study end point, HbA1c was reduced from baseline with nateglinide and metformin but was increased with placebo (-0.5, -0.8, and +0.5%, respectively; P < or = 0.0001). Changes in FPG followed the same pattern (-0.7, -1.6, and +0.4 mmol/l; P < or = 0.0001). Combination therapy was additive (HbA1c -1.4% and FPG -2.4 mmol/l; P < or = 0.01 vs. monotherapy). After Sustacal challenge, there was a greater reduction in mealtime glucose with nateglinide monotherapy compared with metformin monotherapy or placebo (adjusted area under the curve [AUC]0-130 min -2.1, -1.1, and -0.6 mmol x h(-1) x l(-1); p < or = 0.0001). An even greater effect was observed with combination therapy (AUC0-130 min -2.5 mmol x h(-1) x l(-1); P < or = 0.0001 vs. metformin and placebo). All regimens were well tolerated. CONCLUSIONS: Nateglinide and metformin monotherapy each improved overall glycemic control but by different mechanisms. Nateglinide decreased mealtime glucose excursions, whereas metformin primarily affected FPG. In combination, nateglinide and metformin had complementary effects, improving HbA1c, FPG, and postprandial hyperglycemia.     

Twelve- and 52-week efficacy of the dipeptidyl peptidase IV inhibitor LAF237 in metformin-treated patients with type 2 diabetes

OBJECTIVE: To assess the 12- and 52-week efficacy of the dipeptidyl peptidase IV inhibitor LAF237 versus placebo in patients with type 2 diabetes continuing metformin treatment. RESEARCH DESIGN AND METHODS: We conducted a 12-week, randomized, double-blind, placebo-controlled trial in 107 patients with type 2 diabetes with a 40-week extension in those completing the core study and agreeing, together with the investigator, to extend treatment to 1 year. Placebo (n=51) or LAF237 (50 mg once daily, n=56) was added to ongoing metformin treatment (1,500-3,000 mg/day). HbA1c and fasting plasma glucose (FPG) were measured periodically, and standardized meal tests were performed at baseline, week 12, and week 52. RESULTS: In patients randomized to LAF237, baseline HbA1c averaged 7.7 +/- 0.1% and decreased at week 12 (Delta=-0.6 +/- 0.1%), whereas HbA1c did not change from a baseline of 7.9 +/- 0.1% in patients given placebo (between-group difference in DeltaHbA1c=-0.7 +/- 0.1%, P <0.0001). Mean prandial glucose and FPG were significantly reduced in patients receiving LAF237 versus placebo by 2.2 +/- 0.4 mmol/l (P <0.0001) and 1.2 +/- 0.4 mmol/l (P=0.0057), respectively, but plasma insulin levels were not affected. At end point of the extension, the between-group differences in change in mean prandial glucose, insulin, and FPG were -2.4 +/- 0.6 mmol/l (P=0.0001), 40 +/- 16 pmol/l (P=0.0153), and -1.1 +/- 0.5 mmol/l (P=0.0312), respectively. HbA1c did not change from week 12 to week 52 in LAF237-treated patients (n=42) but increased in participants given placebo (n=29). The between-group difference in DeltaHbA1c after 1 year was -1.1 +/- 0.2% (P <0.0001). CONCLUSIONS: Data from this study demonstrate that LAF237 effectively prevents deterioration of glycemic control when added to metformin monotherapy in type 2 diabetes.     

Prevalence of diabetes estimated by plasma glucose criteria combined with standardized measurement of HbA1c among health checkup participants on Miyako Island, Japan

OBJECTIVE: To estimate the prevalence of diabetes in participants of an annual health checkup in the district of the Miyako Public Health Center (Okinawa, Japan) by using the revised criteria of the Japan Diabetes Society (JDS). RESEARCH DESIGN AND METHODS: The subjects studied here were all Japanese and 45-75 years of age at the time of the health examination in 1998. Diagnosis of diabetes was based on the following: 1) fasting plasma glucose > or =7.0 mmol/l, 2) casual plasma glucose > or =11.1 mmol/l, 3) HbA(1c) > or =6.1%, and 4) self-report on a special questionnaire given at the examination. The HbA(1c) value was standardized by the measurement of 2 standard samples provided by the JDS. RESULTS: Among the 2,621 subjects, 59.7% had their fasting blood glucose levels measured. Of the subjects diagnosed as having diabetes, 154 (12.6%) were men and 115 (8.6%) women. Among the subjects newly diagnosed with diabetes from their fasting blood glucose levels. 27.5% of the men and 21.9% of the women had diagnoses based on HbA(1c) alone. Overall, 34.9% of the subjects with newly diagnosed diabetes were identified by plasma glucose (PG) alone and 33.0% were diagnosed by HbA(1c) alone. CONCLUSIONS: The combination of PG and HbA(1c) resulted in a considerable increase in newly diagnosed diabetes as compared with the use of only one of these parameters. Considering the convenience and correlation with vascular complications, use of the 2 tests may be beneficial in epidemiological studies of the Japanese population to identify high-risk groups for micro- and macrovascular diseases.     

The treat-to-target trial: randomized addition of glargine or human NPH insulin to oral therapy of type 2 diabetic patients

OBJECTIVE: To compare the abilities and associated hypoglycemia risks of insulin glargine and human NPH insulin added to oral therapy of type 2 diabetes to achieve 7% HbA(1c). RESEARCH DESIGN AND METHODS: In a randomized, open-label, parallel, 24-week multicenter trial, 756 overweight men and women with inadequate glycemic control (HbA(1c) >7.5%) on one or two oral agents continued prestudy oral agents and received bedtime glargine or NPH once daily, titrated using a simple algorithm seeking a target fasting plasma glucose (FPG) 相似文献   

Efficacy and safety of pioglitazone in type 2 diabetes: a randomised,placebo-controlled study in patients receiving stable insulin therapy

The glycaemic and lipid effects of treatment with pioglitazone in combination with a stable insulin regimen were evaluated in patients with type 2 diabetes. Patients (n=566) receiving stable insulin regimens for > or = 30 days yet who had HbA1c > or = 8.0% and C-peptide > 0.7 microg/l were randomised to receive once-daily 15 mg pioglitazone, 30 mg pioglitazone, or placebo in a 16-week multicentre, double-blind, placebo-controlled trial. Per study protocol, the insulin dose was to remain unchanged, but could be decreased in response to hypoglycaemia. At the end of double-blind treatment, patients receiving pioglitazone (15 mg or 30 mg) showed statistically significant mean decreases relative to baseline HbA1c (-1.0 and -1.3, respectively; p<0.0001) and fasting plasma glucose (FPG) (-34.5 mg/dl [-1.92 mmol/l] and -48.0 mg/dl [-2.67 mmol/l], respectively; p<0.0001); these differences compared with placebo were also significant (p<0.0001). Pioglitazone (15 or 30 mg) yielded significant increases in HDL-C levels (mean increases ranging from +7.1% to + 9.3%) compared with baseline or placebo (p<0.01). The 30 mg dose also significantly reduced mean triglyceride levels (-23.7%) compared with placebo (p=0.0218). No consistent changes in TC or LDL-C levels were observed. The incidence of adverse events was similar in all treatment groups, although the incidences of weight increase, hypoglycaemia and oedema were higher among patients receiving insulin plus pioglitazone. There was no evidence of hepatotoxicity or drug-induced elevations of serum ALT > or = 3 x ULN. Pioglitazone, when added to stable insulin regimens, significantly improved HbA1c and FPG in type 2 diabetes. Pioglitazone treatment also provided significant benefit with respect to plasma HDL-C and triglyceride levels. Whether these lipid changes have an impact on overall diabetic complications remains to be determined.     

Use of HbA1c in predicting progression to diabetes in French men and women: data from an Epidemiological Study on the Insulin Resistance Syndrome (DESIR)

OBJECTIVE: Early identification of subjects at high risk for diabetes is essential, and random HbA(1c) (A1C) may be more practical than fasting plasma glucose (FPG). The predictive value of A1C, in comparison to FPG, is evaluated for 6-year incident diabetes. RESEARCH DESIGN AND METHODS: From the French cohort study Data from an Epidemiological Study on the Insulin Resistance Syndrome (DESIR), 1,383 men and 1,437 women, aged 30-65 years, were volunteers for a routine health check-up. Incident diabetes was defined by FPG >or=7.0 mmol/l or treatment by antidiabetic drugs. Multivariate logistic regression models were used to predict diabetes at 6 years. Receiver operating characteristic curves compared the predictive values of A1C and FPG. RESULTS: At 6 years, 30 women (2.1%) and 60 men (4.3%) had developed diabetes. Diabetes risk increased exponentially with A1C in both sexes (P < 0.001). After stratifying on FPG, A1C predicted diabetes only in subjects with impaired fasting glucose (IFG) (FPG >or=6.10 mmol/l): the odds ratio (95% CI) for a 1% increase in A1C was 7.20 (3.00-17.00). In these subjects, an A1C of 5.9% gave an optimal sensitivity of 64% and specificity of 77% to predict diabetes. CONCLUSIONS: A1C predicted diabetes, even though the diagnosis of diabetes was based on FPG, but it was less sensitive and specific than FPG. It could be used as a test if fasting blood sampling was not available or in association with FPG. In subjects with IFG, A1C is better than glucose to evaluate diabetes risk, and it could be used to select subjects for intensive early intervention.     

Using HbA(1c) to improve efficacy of the american diabetes association fasting plasma glucose criterion in screening for new type 2 diabetes in American Indians: the strong heart study

OBJECTIVE: To find an optimal critical line in the fasting plasma glucose (FPG)-HbA(1c) plane for identifying diabetes in participants with impaired fasting glucose (IFG) and thereby improve the efficacy of using FPG alone in diabetes screening among American Indians. RESEARCH DESIGN AND METHODS: We used FPG, 2-h postload glucose (2hPG), and HbA(1c) measured in the 2,389 American Indians (aged 45-74 years, without diabetes treatment or prior history of diabetes) in the Strong Heart Study (SHS) baseline (second) examination. Participants were classified as having diabetes if they had either FPG > or =126 mg/dl or 2hPG > or =200 mg/dl, as having IFG if they had 110 < or = FPG < 126 mg/dl, and as having normal fasting glucose (NFG) if they had FPG <110, according to the American Diabetes Association (ADA) definition. Logistic regression models were used for identifying diabetes (2hPG > or =200 mg/dl) in IFG participants. The areas under the receiver operating characteristic (ROC) curves generated by different logistic regression models were evaluated and compared to select the best model. A utility function based on the best model and the cost-to-benefit ratio was used to find the optimal critical line. The data from the second examination were used to study the effect of the time interval between the successive diabetes screenings on both the FPG criterion and the optimal critical line. RESULTS: A total of 37% of all subjects with new diabetes at baseline and 55.2% of those in the second exam had 2hPG > or =200 but FPG <126. There was a very large portion of IFG participants with diabetes (19.3 and 22.9% in the baseline and second exam, respectively). Among the areas under the ROC curves, the area generated by the logistic regression model on FPG plus HbA(1c) is the largest and is significantly larger than that based on FPG (P = 0.0008). For a cost-to-benefit ratio of 0.23888, the optimal critical line that has the highest utility is: 0.89 x HbA(1c) + 0.11 x FPG = 17.92. Those IFG participants whose FPG and HbA(1c) were above or on the line were referred to take an oral glucose tolerance test (OGTT) to diagnose diabetes. The optimal critical line is lower if a successive diabetes screening will be conducted 4 years after the previous screening. CONCLUSIONS: FPG > or =126 and 2hPG > or =200, as suggested by the ADA, are used independently to define diabetes. The FPG level is easy to obtain, and using FPG alone is suggested for diabetes screening. It is difficult to get physicians and patients to perform an OGTT to get a 2hPG level because of the many drawbacks of the OGTT, especially in those patients who already have FPG <126. It is also impractical to conduct an OGTT for everyone in a diabetes screening. Our data show that 37% of all subjects with new diabetes in the SHS baseline exam and 55.2% of those in the second exam have 2hPG > or =200 but FPG <126. These cases of diabetes cannot be detected if FPG is used alone in a diabetes screening. Therefore, although the small portion of diabetes in the NFG group (4.7% in the baseline and 6.9% in the second exam) may be ignored, those cases of diabetes among IFG participants ( approximately 20% in our data) need further consideration in a diabetes screening. It may be worthwhile for those IFG participants identified by the optimal critical line to take an OGTT. The optimal critical line and time interval between successive diabetes screenings need further study.     

Plasma glucose levels throughout the day and HbA(1c) interrelationships in type 2 diabetes: implications for treatment and monitoring of metabolic control.

OBJECTIVE: To evaluate the extent of plasma glucose excursions with meals, the relations between plasma glucose levels at different times of the day, and the relations between the latter and HbA(1c) in non-insulin-treated type 2 diabetic subjects. RESEARCH DESIGN AND METHODS: Daily glucose profiles were assessed in non-insulin-treated type 2 diabetic patients. Outpatients at the diabetes clinic (n = 371; one daily plasma glucose profile) and at home (n = 30; five daily blood glucose profiles over 1 month) as well as inpatients (n = 455; profile of plasma glucose on the day of admission) were examined. Subjects had plasma/blood glucose assessment before and 2-3 h after breakfast, lunch, and dinner. HbA(1c) was also measured. RESULTS: After the meals many subjects had glucose levels >8.9 mmol/l (160 mg/dl) and/or glucose excursions >2.2 mmol/l (40 mg/dl). This was also often found when HbA(1c) was satisfactory (<7%). The coefficients of simple correlation among plasma/blood glucose at different times of the day ranged from 0.52 to 0.88. Correlations between HbA(1c) and plasma/blood glucose at different times of the day ranged from 0.44 to 0.67. The strongest correlation was between HbA(1c) and mean daily glucose (r = 0.57-0.69). Multiple regression analyses showed that premeal but not postmeal plasma/blood glucose levels were independent predictors of HbA(1c). CONCLUSIONS: These results suggest that 1) the majority of non-insulin-treated type 2 diabetic patients have exaggerated plasma/blood glucose excursions with meals, and many of them have higher-than-recommended glucose concentrations 2 h after the meals; 2) plasma/blood glucose levels throughout the day are not as strongly interrelated as one might believe; and 3) HbA(1c) is more related to preprandial than postprandial plasma/blood glucose levels. These findings have potential implications for treatment and monitoring of metabolic control in type 2 diabetes.     

糖化血红蛋白联合空腹血糖筛查2型糖尿病高危人群的临床意义

目的了解糖化血红蛋白(HbA1c)筛查糖尿病和糖代谢受损的敏感性并与空腹血糖(FBG)进行比较。方法对400例无糖尿病病史的糖尿病高危人群同时检测FBG和HbA1c,据空腹血糖水平分为三组:A1组:FBG<6.1 mmol/L,计336例,A2组:FBG 6.1-6.9 mmol/L,45例,A3组FBG≥7.0 mmol/L,19例。结果 (1)400例人群中,HbA1c≥6.0%,88例,异常率为22.0%;FBG≥6.1mmol/L,54例,异常率13.5.%,HbA1c的异常率高于FBG,P<0.05。(2)A1组HbA1c>≥6.0%,29例,占8.6%;A2组HbA1c≥6.0%,41例,占91.1%;A3组HbA1c≥6.0%,18例,占94.7%;(3)400例人群中,HbA1c≥6.0%或FBG≥6.1mmol/L,93例,异常率23.3%%。结论 HbA1c筛查糖尿病高危人群血糖异常的敏感性高于空腹血糖,两者联合检查有助发现更多糖代谢异常的患者。     

Plasma glucose and prediction of microvascular disease and mortality: evaluation of 1997 American Diabetes Association and 1999 World Health Organization criteria for diagnosis of diabetes

OBJECTIVE: The 1997 American Diabetes Association (ADA) and 1999 World Health Organization (WHO) criteria for diabetes and hyperglycemia were evaluated and compared with respect to prediction of microvascular and macrovascular disease and mortality RESEARCH DESIGN AND METHODS: The prevalence of retinopathy and nephropathy at baseline and during the subsequent 10 years and mortality rates were examined in relation to baseline fasting plasma glucose (FPG) and 2-h postload plasma glucose (2-h PG) among 5,023 Pima Indian adults and in relation to the cut points defined by the ADA and WHO criteria. RESULTS: The frequencies of retinopathy and nephropathy were directly related to baseline FPG and 2-h PG with approximate thresholds near or below the current diagnostic criteria for diabetes (FPG > or =7.0 and 2-h PG > or = 11.1 mmol/l). The rates of retinopathy were 4.7% in impaired fasting glucose (IFG) and 20.9% in diabetes by ADA criteria; 1.6% for impaired glucose tolerance (IGT) and 19.7% for diabetes by 1985 WHO criteria; and 1.2% for IGT and 19.2% for diabetes by the 1999 WHO criteria. Mortality rates from cardiovascular-renal-related diseases were higher in diabetic individuals (FPG > or =7.0 or 2-h PG > 11.1 mmol/l) than in those with normal FPG and 2-h PG but were not elevated in those with IFG or IGT. CONCLUSIONS: Retinopathy and nephropathy were directly related to higher FPG or 2-h PG. FPG, which identifies those at high risk of microvascular disease and mortality, can be used to predict these outcomes and to diagnose diabetes when oral glucose tolerance testing is not practical.     

Diabetic patients detected by population-based stepwise screening already have a diabetic cardiovascular risk profile

OBJECTIVE: To describe a population-based two-step screening procedure for type 2 diabetes and to study the cardiovascular risk profile of the patients identified by the screening. RESEARCH DESIGN AND METHODS: The first step of the screening procedure consisted of the Symptom Risk Questionnaire (SRQ), and the second step was a fasting capillary glucose measurement. In subjects with an SRQ score of >6 and a capillary glucose level of >5.5 mmol/l, an oral glucose tolerance test was performed. RESULTS: A total of 11,679 inhabitants of the West-Friesland region of the Netherlands, aged 50-75 years, were invited. Of the inhabitants, 9,169 (78%) responded, and, of those, 417 had previously diagnosed diabetes. The SRQ score was calculated for 7,736 participants, and 3,301 of those had a score of >6. A total of 2,885 subjects (87.3%) attended for capillary glucose measurement. Diagnostic testing was carried out in 509 participants, and we identified 217 diabetic patients. In these patients detected by screening, mean HbA(1c) was 6.7% (+/-1.4). Hypertension and high total cholesterol levels (>5.0 mmol/l) were present in 70%, 33% had high triglyceride (>3.0 mmol/l) or low HDL cholesterol levels (<1.0 mmol/l in men and <1.1 mmol/l in women), and 40% were obese (BMI > or =30 kg/m(2)). CONCLUSIONS: The high response rate was the main feature of the screening by means of the Symptom Risk Questionnaire and fasting capillary glucose measurement followed by diagnostic testing. The 217 diabetic patients detected by the screening were characterized by relatively low HbA(1c) levels and by a cardiovascular risk profile typical of diabetic patients.     

The prevalence of diabetes in the kingdom of Tonga

OBJECTIVE: To determine the prevalence of diabetes, impaired glucose metabolism, and related risk factors in Tonga. RESEARCH DESIGN AND METHODS: A randomly selected representative national sample of 1,024 people aged >15 years was surveyed. Each participant had fasting blood glucose and HbA(1c) measured. Subjects with a fasting blood glucose >5.0 mmol/l (90 mg/dl) and <11.1 mmol/l (200 mg/dl) or a fasting blood glucose < or =5.0 mmol/l and an HbA(1c) >6.0% and every fifth subject with a fasting blood glucose < or =5.0 mmol/l and a normal HbA(1c) had a 75-g oral glucose tolerance test (OGTT). A total of 472 individuals had an OGTT based on these criteria. Subjects with a fasting blood glucose > or =11.1 mmol/l and an elevated HbA(1c) were diagnosed as having diabetes. RESULTS: The mean age was 41.3 years, and the mean BMI was 32.3 kg/m(2). The age-standardized prevalence of diabetes was 15.1% (CI 12.5-17.6), 12.2% (8.7-15.8) in men and 17.6% (14.0-21.1) in women (NS), of which only 2.1% was previously diagnosed. A total of 75% of people with newly diagnosed diabetes had a fasting plasma glucose > or =7.0 mmol/l (126 mg/dl). The prevalence of impaired glucose tolerance was 9.4% (7.3-11.5) and of impaired fasting glycemia 1.6% (0.7-2.6). Undiagnosed diabetes was significantly associated with increasing age, obesity, hypertension, and a family history of diabetes. CONCLUSIONS: The current prevalence of diabetes in Tonga is 15.1%, of which 80% is undiagnosed. A similar survey in 1973 reported a 7.5% diabetes prevalence, indicating a doubling of diabetes over the past 25 years. In addition, lesser degrees of glucose intolerance are common, and much of the community is overweight