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.     

Combined use of fasting plasma glucose and HbA1c predicts the progression to diabetes in Chinese subjects

OBJECTIVE: We have previously suggested using the paired values of fasting plasma glucose (FPG) and HbA1c to identify potential diabetic subjects. In this article, we followed up on 208 nondiabetic subjects and examined their rates of progression to diabetes. We analyzed their likelihood of becoming diabetic according to their baseline FPG and HbA1c concentrations. RESEARCH DESIGN AND METHODS: Between 1988 and 1995, 2,877 Chinese subjects with risk factors for diabetes underwent screening. Of these, 2,250 had FPG <7.8 mmol/l and 2-h plasma glucose (PG) <11.1 mmol/l. Of these 2,250 subjects, 265 were randomly recruited for an annual oral glucose tolerance test (OGTT) until they progressed to develop diabetes. Of those 265 subjects, 57 had baseline FPG > or =7.0 mmol/l and were excluded from the present analysis. Hence, the progression of glucose tolerance in 208 subjects who were nondiabetic according to the new American Diabetes Association diagnostic criteria (FPG < 7.0 mmol/l and 2-h PG < 11.1 mmol/l) was examined RESULTS: Of the 208 nondiabetic subjects, 26 (12.5%) were men and 182 (87.5%) were women. After a mean follow-up of 1.60 +/- 1.16 years (range 1-7, median 1), 44 (21.2%) progressed to develop diabetes and 164 (78.8%) remained nondiabetic. Those who were diabetic at the end of the study had a high likelihood ratio (LR) of 9.3 to have baseline FPG > or =6.1 mmol/l and baseline HbA1c > or =6.1%. This was compared with a low LR of 0.6-1.1 in diabetic subjects who had either FPG <6.1 mmol/l or HbA1c <6.1% or both at baseline. The crude rate of progression to diabetes was more than five times higher (44.1 vs. 8.1%) in those whose baseline FPG was > or =6.1 mmol/l and baseline HbA1c was > or =6.1% compared with those whose baseline FPG was <6.1 mmol/l and baseline HbA1c was <6.1%. CONCLUSIONS: For Chinese subjects with risk factors for glucose intolerance, the use of paired FPG and HbA1c values helped to identify potential diabetic subjects. Those with an FPG > or =6.1 mmol/l and HbA1c > or =6.1% had a rate of progression to diabetes more than five times higher than those with an FPG <6.1 mmol/l and an HbA1c <6.1% after a mean follow-up of 1.6 years. Those with an FPG > or =6.1 but <7.0 mmol/l, especially if their HbA1c was > or =6.1%, should undergo an OGTT to confirm diabetes. Subjects with an FPG <6.1 mmol/l and/or an HbA1c <6.1% should have regular screening using the paired values of FPG and HbA1c.     

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."     

Screening for type 2 diabetes and impaired glucose metabolism: the Australian experience

OBJECTIVE: To assess the Australian protocol for identifying undiagnosed type 2 diabetes and impaired glucose metabolism. RESEARCH DESIGN AND METHODS: The Australian screening protocol recommends a stepped approach to detecting undiagnosed type 2 diabetes based on assessment of risk status, measurement of fasting plasma glucose (FPG) in individuals at risk, and further testing according to FPG. The performance of and variations to this protocol were assessed in a population-based sample of 10,508 Australians. RESULTS: The protocol had a sensitivity of 79.9%, specificity of 79.9%, and a positive predictive value (PPV) of 13.7% for detecting undiagnosed type 2 diabetes and sensitivity of 51.9% and specificity of 86.7% for detecting impaired glucose tolerance (IGT) or impaired fasting glucose (IFG). To achieve these diagnostic rates, 20.7% of the Australian adult population would require an oral glucose tolerance test (OGTT). Increasing the FPG cut point to 6.1 mmol/l (110 mg/dl) or using HbA(1c) instead of FPG to determine the need for an OGTT in people with risk factors reduced sensitivity, increased specificity and PPV, and reduced the proportion requiring an OGTT. However, each of these protocol variations substantially reduced the detection of IGT or IFG. CONCLUSIONS: The Australian screening protocol identified one new case of diabetes for every 32 people screened, with 4 of 10 people screened requiring FPG measurement and 1 in 5 requiring an OGTT. In addition, 1 in 11 people screened had IGT or IFG. Including HbA(1c) measurement substantially reduced both the number requiring an OGTT and the detection of IGT or IFG.     

Is using WHO criteria for impaired fasting glycaemia appropriate as an indication for OGTT in patients at high risk of developing diabetes?

Aim: Impaired fasting glycaemia (IFG) is an indication for oral glucose tolerance test (OGTT). World health organisation and International Diabetes Federation define IFG as fasting plasma glucose (FPG) levels of 6.1–6.9 mmol/l. However, American Diabetes Association still recommends a range of 5.6–6.9 mmol/l as IFG. We performed an audit to assess the outcome of OGTT at various cut offs of FPG levels in patients at high risk of developing diabetes. Methods: Laboratory data on OGTT performed over a period of 1 year in a district general hospital were collected. Patients with FPG levels between 5.6 and 6.9 mmol/l were selected and the outcome was analysed. Results: Our audit shows that in patients with FPG levels of 5.6–6.0 mmol/l, 19% had diabetes and 43% had impaired glucose tolerance (IGT). Conclusion: The percentage of subjects with abnormal OGTT in our study is much higher than that of Decode study [Diabetologica, 42 (1999) 647] (7% diabetes and 29% IGT). However, Decode study had included general population whereas our data were collected from subjects who are at high risk of developing diabetes. We conclude that in these subjects the lower cut off level of 5.6 mmol/l for FPG should be used as an indication for OGTT.     

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     

Postchallenge plasma glucose and glycemic spikes are more strongly associated with atherosclerosis than fasting glucose or HbA1c level

OBJECTIVE: To observe the relationship of fasting plasma glucose (FPG), postchallenge plasma glucose (PG) (30, 60, 90, and 120 min during an oral glucose tolerance test [OGTT], as well as maximal PG during an OGTT, postchallenge glucose spikes [PGS], and glucose under the OGTT curve), and HbA1c to intima-media thickness (IMT) as a marker of atherosclerosis. RESEARCH DESIGN AND METHODS: OGTT, ultrasound measurement of carotid IMT, and various atherosclerosis risk factors, such as family history of diabetes, obesity, and/or hyperlipoproteinemia, but without known diabetes, were analyzed in 582 individuals aged 40-70 years and at risk for type 2 diabetes. RESULTS: In univariate analysis, all examined glycemic parameters were significantly correlated to IMT. The 2-h postchallenge plasma glucose showed the strongest odds ratio (OR) of 1.88 (1.34-2.63) in relation to abnormal IMT. All PG variables, except for 30-min glucose in OGTT, showed a significant OR, whereas the OR for HbA1c and FPG was not significant. In logistic regression analysis, 2-h PG was identified as the strongest determinant of IMT from all glycemic parameters. The 2-h PG and PGS, but not FPG, were associated with a significant rise of IMT in tertiles of HbA1c. Glycemic parameters were strongly related to each other and to many atherosclerosis risk factors. In multivariate analysis including a variety of atherosclerosis risk factors, 2-h PG was a significant independent determinant of IMT. CONCLUSIONS: PG and PGS are more strongly associated with carotid IMT than FPG and HbA1c level and modify substantially the risk for atherosclerosis, estimated by HbA1c alone, in a cohort at risk for diabetes and in the early diabetes stage.     

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   

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.     

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.     

糖化血红蛋白和血糖水平检测对精神病患者并发糖尿病的诊断价值

目的探讨糖化血红蛋白(HbA1c)、空腹血糖(FPG)、葡萄糖耐量试验(OGTT)2 h血糖检测对精神病并发糖尿病诊断的临床价值。方法收集重庆市精神卫生中心歌乐山院区老年科及综合科107例精神病并发糖尿病患者纳入观察组,110例非糖尿病的精神病患者纳入疾病对照组,100例职工健康体检者纳入健康对照组。采集血清及抗凝全血标本,采用己糖激酶法测定FPG、OGTT 2 h血糖,采用液相色谱离子交换层析法检测HbA1c水平,比较3组研究对象各项指标水平,并分析观察组各项指标相关性及并发症发生情况。结果观察组患者的FPG、OGTT 2 h血糖、HbA1c水平均明显高于疾病对照组和健康对照组,差异有统计学意义(P<0.05);疾病对照组和健康对照组的FPG、OGTT 2 h血糖、HbA1c水平比较,差异无统计学意义(P>0.05)。观察组中,FPG与HbA1c呈显著正相关(r=0.591,P<0.05);OGTT 2 h血糖水平与HbA1c水平呈显著正相关(r=0.564,P<0.05)。HbA1c>8%患者相关并发症的发生率均明显高于HbA1c≤8%患者,差异有统计学意义(P<0.05)。结论FPG、OGTT和HbA1c水平检测可作为诊断精神病患者并发糖尿病的一项重要指标,且对并发症发生风险具有重要的评估价值。     

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.     

The relation of fasting and 2-h postchallenge plasma glucose concentrations to mortality: data from the Baltimore Longitudinal Study of Aging with a critical review of the literature

OBJECTIVE: Under the auspices of the National Institutes of Health, American Diabetes Association, and World Health Organization, expert committees lowered the fasting plasma glucose (FPG) concentration diagnostic for diabetes from 7.8 to 7.0 mmol/l and defined 6.1-6.9 mmol/l as impaired fasting glucose (IFG) and <6.1 mmol/l as normal fasting glucose. In 2003, IFG was lowered to 5.6-6.9 mmol/l and normal fasting glucose to <5.6 mmol/l. Reports of the relationship between glucose concentration and all-cause mortality have been inconsistent. It is not known if the 2-h plasma glucose (2hPG) concentration from an oral glucose tolerance test (OGTT) adds to the predictive power of FPG. RESEARCH DESIGN AND METHODS: We followed 1,236 men for an average of 13.4 years to determine the relationship between both FPG and 2hPG and all-cause mortality. RESULTS: Risk for mortality did not increase until the FPG exceeded 6.1 mmol/l. Risk increased by approximately 40% in the 6.1-6.9 mmol/l range and doubled when FPG ranged from 7.0 to 7.7 mmol/l. A combination of the 2hPG and FPG allowed better estimation of risk than the FPG alone. Within any category of FPG, risk generally increased as the 2hPG increased, and within any category of 2hPG, risk generally increased as the FPG increased. CONCLUSIONS: These data support the decision to lower the FPG diagnostic for diabetes from 7.8 to 7.0 mmol/l, show that both IFG and impaired glucose tolerance have risks between the normal and diabetic ranges, and show that the OGTT adds predictive power to that of FPG alone and should not be abandoned. The lowering of IFG to 5.6 mmol/l from 6.1 mmol/l, at least for mortality, is, however, not supported by our results.     

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.     

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.     

血清FPG 及HbA1c 水平检测对2 型糖尿病继发干眼症的预测价值研究及危险因素分析

目的　探讨血清空腹血糖（fasting blood glucose,FPG）及糖化血红蛋白（glycosylated hemoglobin,HbA1c） 水平检测对2 型糖尿病继发干眼症的预测价值研究及危险因素分析。方法　选择唐山市眼科医院2017 年8 月～ 2019 年8 月收治的60 例2 型糖尿病继发干眼症患者为干眼症组,另外纳入同期于该院治疗的60 例2 型糖尿病患者为糖尿 病组。对比两组基础资料（年龄、性别、病程、泪腺功能、胰岛素分泌以及FPG,HbA1c 水平）,采用ROC 曲线分析 FPG,HbA1c 水平预测2 型糖尿病患者发生干眼症价值;采用Logistic 回归分析模型,明确2 型糖尿病患者发生干眼症 的危险因素。结果　经单因素分析,两组年龄、性别以及病程比较,差异无统计学意义（t=0.134, χ2=0.186,t=0.223, 均P ＞ 0.05）;干眼症组存在泪腺功能障碍、胰岛素分泌不足患者显著多于糖尿病组,差异有统计学意义（χ2=5.829,8.336, 均P ＜ 0.05）;干眼症组FPG,HbA1c 水平显著高于糖尿病组,差异有统计学意义（t=2.922,5.925,均P ＜ 0.05）。 经ROC分析FPG 和HbA1c 的曲线下面积分别为0.738 和0.701,标准差分别为0.045 和0.047,95%CI 分别为0.651 ～ 0.825 和0.609~0.794,最佳截断值分别为8.765mmol/L 和6.875%,敏感度分别为0.567 和0.933,特异度分别为0.750 和0.400。 经Logistic 回归性分析证实存在泪腺功能障碍、胰岛素分泌不足、FPG ＞ 8.765mmol/L 以及HbA1c ＞ 6.875% 是2 型糖 尿病患者发生干眼症的危险因素。结论　影响2 型糖尿病患者发生干眼症的危险因素较多,如存在泪腺功能障碍、胰岛 素分泌不足以及FPG,HbA1c,其中FPG ＞ 8.765mmol/L 和HbA1c ＞ 6.875% 是预测2 型糖尿病患者发生干眼症的最佳 截断值,在预防2 型糖尿病患者发生干眼症的过程中具有一定的参考价值,临床应当关注。     

What is a normal glucose value? Differences in indexes of plasma glucose homeostasis in subjects with normal fasting glucose

OBJECTIVE: To evaluate differences in indexes of plasma glucose/insulin homeostasis and cardiovascular disease risk factors among subjects with normal fasting glucose (NFG), impaired fasting glucose, or glucose intolerance. Although individuals with fasting plasma glucose (FPG) concentrations > 5.4 mmol/l but < 6.1 mmol/l have been shown to have an increased risk of developing type 2 diabetes over 5 years, little is known about glucose metabolism abnormalities in this population. RESEARCH DESIGN AND METHODS: We compared insulin secretion and insulin sensitivity using several indexes derived from an oral glucose tolerance test (OGTT) in 668 subjects from the Quebec Family Study who had varying degrees of FPG. RESULTS: There was a progressive decline in indexes of beta-cell function and insulin sensitivity when moving from NFG to type 2 diabetes. Compared with subjects with low NFG (FPG < 4.9 mmol/l), subjects with high NFG (FPG 5.3-6.1 mmol/l) were more insulin resistant (P < 0.01), had higher insulin and C-peptide responses during an OGTT (P < 0.05), and had reduced insulin secretion (corrected for insulin resistance). Subjects with high NFG were also characterized by higher plasma triglyceride levels and reduced HDL cholesterol concentrations and by a smaller LDL particle size. All these differences remained significant, even after adjustment for age, sex, BMI, and waist circumference. In addition, subjects with mid NFG (FPG 4.9-5.3 mmol/l) were characterized by impaired insulin secretion, decreased insulin sensitivity, higher triglyceride concentrations, and lower HDL cholesterol concentrations compared with subjects with low NFG. CONCLUSIONS: Independent of age, sex, and adiposity, there are differences in indexes of plasma glucose/insulin homeostasis and in cardiovascular risk factors among subjects with low, mid, and high NFG, suggesting the presence, in the upper normal glucose range, of abnormalities in glucose homeostasis, which may predispose to type 2 diabetes.     

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.     

Fasting plasma glucose and hemoglobin A1c in identifying and predicting diabetes: the strong heart study

OBJECTIVE: To compare fasting plasma glucose (FPG) and HbA(1c) in identifying and predicting type 2 diabetes in a population with high rates of diabetes. RESEARCH DESIGN AND METHODS: Diabetes was defined as an FPG level ≥ 126 mg/dL or an HbA(1c) level ≥ 6.5%. Data collected from the baseline and second exams (1989-1995) of the Strong Heart Study were used. RESULTS For cases of diabetes identified by FPG ≥ 126 mg/dL, using HbA(1c) ≥ 6.5% at the initial and 4-year follow-up diabetes screenings (or in identifying incident cases in 4 years) among undiagnosed participants left 46% and 59% of cases of diabetes undetected, respectively, whereas for cases identified by HbA(1c) ≥ 6.5%, using FPG ≥ 126 mg/dL left 11% and 59% unidentified, respectively. Age, waist circumference, urinary albumin-to-creatinine ratio, and baseline FPG and HbA(1c) levels were common significant risk factors for incident diabetes defined by either FPG or HbA(1c); triglyceride levels were significant for diabetes defined by HbA(1c) alone, and blood pressure and sibling history of diabetes were significant for diabetes defined by FPG alone. Using both the baseline FPG and HbA(1c) in diabetes prediction identified more people at risk than using either measure alone. CONCLUSIONS Among undiagnosed participants, using HbA(1c) alone in initial diabetes screening identifies fewer cases of diabetes than FPG, and using either FPG or HbA(1c) alone cannot effectively identify diabetes in a 4-year periodic successive diabetes screening or incident cases of diabetes in 4 years. Using both criteria may identify more people at risk. The proposed models using the commonly available clinical measures can be applied to assessing the risk of incident diabetes using either criterion.     

初诊2型糖尿病患者尿微量白蛋白/肌酐比值异常的发生率及危险因素分析

目的 分析初诊2型糖尿病患者尿微量白蛋白/肌酐比值(ACR)异常的发生率及危险因素.方法 2008年9月至2009年12月我院内分泌科收治的初诊2型糖尿病患者245例,测定空腹血糖(FPG),葡萄糖耐量试验、血脂、肾功能及尿ACR等.分别根据患者年龄、糖化血红蛋白(HbA1c)及尿ACR水平进行分层.采用t检验、方差分析、多元逐步回归分析等方法进行统计学分析.结果 ①本研究人群中,尿ACR的异常率为21.6%,其中微量白蛋白尿20.4%,大量白蛋白尿1.2%.②不同年龄组患者尿ACR水平＜40岁组(26.4±34.2)mg/g、≥40～50岁组(33.7±68.5)mg/g、≥50～59岁组(38.6±94.9)mg/g、≥60～69岁组(33.9±60.8)mg/g、≥70岁组(48.9±62.4)mg/g,差异无统计学意义(F=0.400,P＞0.05).③异常尿ACR组FPG、收缩压(SBP)、甘油三酯(TG)、体质量指数(BMI)显著高于正常尿ACR组患者(t值分别为-2.547、-2.144、-2.113、-4.663,P＜0.05或＜0.01),高密度胆固醇(HDL-C)显著低于正常尿ACR组(t=2.216,P＜0.05).④HbA1 c≥6.5%组的尿ACR水平与HbA1c＜6.5%组的差异无统计学意义(t=0.475,P＞0.05),HbA1 c≥6.5%组患者合并高血压的尿ACR水平显著高于血压正常患者(t=-2.472,P＜0.05).HbA1c＜6.5%组患者尿ACR比值水平与BMI、FPG呈正相关(r值分别为0.564、0.559,均P＜0.05);HbA1c≥6.5%组尿ACR水平与SBP、舒张压(DBP)和FPG呈正相关(r值分别为0.186、0.169、0.182,均P＜0.05);⑤多元逐步线性回归分析结果,影响尿ACR的主要因素包括FPG、SBP、肌酐(Cr).结论 初诊2型糖尿病患者尿ACR水平异常的发生不受年龄的影响,与血压及FPG有关.