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.     

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.     

空腹血糖及糖化血红蛋白用于筛查糖耐量减退的比较性研究

目的比较空腹血糖（FPG）和糖化血红蛋白（HbAlc）在筛查糖耐量减退（IGT）中的应用价值。方法到我院门诊为明确有无血糖异常而就诊者336人，测定空腹血糖、糖化血红蛋白，并行口服葡萄糖耐量试验（OGTT）。结果按照1999年WHO的DM诊断标准，本研究人群空腹血糖〈6．1者124例，≥6．1-〈7．0者56例，≥7．0者156例；糖化血红蛋白〈6．1者84例，≥6．1者252例；OGTT2 hPG〈7．8者92例，≥7．8-〈11．1者99例，≥11．1者145例。结论糖化血红蛋白和空腹血糖均不适用于筛查IGT人群，但糖化血红蛋白比空腹血糖提示病人是否存在血糖异常更敏感。     

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.     

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.     

The prevalence of diabetes and impaired glucose tolerance in Sivas, Central Anatolia, Turkey

OBJECTIVE: The aim of this study was to determine type 2 diabetes, impaired glucose tolerance (IGT), and impaired fasting glucose (IFG) prevalence in Sivas, Turkey. RESEARCH DESIGN AND METHODS: This cross-sectional study was conducted in the city center of Sivas. The study population of 771 subjects was selected by the cluster sampling method from 115,998 individuals aged > or =30 years. Participants with fasting venous plasma glucose concentrations <100 mg/dl were classified as "normal." Diabetes was diagnosed in participants if they had fasting blood glucose levels > or =126 mg/dl. An oral glucose tolerance test (OGTT) was performed in subjects with fasting blood glucose levels > or =100 mg/dl and <126 mg/dl. RESULTS: According to the fasting blood glucose levels of the 771 subjects, 44 (5.7%) had diabetes. OGTTs were performed in 80 (10.4%) subjects. According to OGTT results, there were 5 subjects with diabetes, 20 subjects with IGT (2.6%), and 55 subjects with IFG (7.1%). The combined prevalence of IFG and IGT was 9.7%. After OGTT, the total number of diabetic subjects was determined to be 49 (6.4%). Twenty-four (3.1%) of the subjects had a previous diagnosis of diabetes. Multivariate analyses showed that age, sex, hypertension, cigarette smoking, obesity, and family history of diabetes were risk factors for type 2 diabetes (P < 0.05). CONCLUSIONS: Diabetes incidence increases with changes in dietary habits and lifestyle. Education is particularly important for public health, as the community may then have required knowledge about the disease and its risk factors.     

Detection of undiagnosed diabetes and other hyperglycemia states: the Atherosclerosis Risk in Communities Study

OBJECTIVE: To evaluate screening strategies based on fasting plasma glucose (FPG), clinical information, and the oral glucose tolerance test (OGTT) for detection of diabetes or other hyperglycemic states-impaired fasting glucose (IFG) and impaired glucose tolerance-meriting clinical intervention. RESEARCH DESIGN AND METHODS: We studied 8,286 African-American and white men and women without known diabetes, aged 53-75 years, who received an OGTT during the fourth exam of the Atherosclerosis Risk in Communities Study. Using a split sample technique, we estimated the diagnostic properties of various clinical detection rules derived from logistic regression modeling. Screening strategies utilizing FPG, these detection rules, and/or the OGTT were then compared in terms of both the fraction of hyperglycemia cases detected and the sample fraction receiving different screening tests and identified as screen positive. RESULTS: Screening based on the IFG cut point (> or =6.1 mmol/l), followed by a clinical detection rule for those below this value, detected 86.3% of diabetic case subjects and 66.0% of all hyperglycemia cases, identifying 42% of the sample as screen positive. Applying an OGTT for those positive by the rule provides diagnostic labeling and reduces the fraction that is screen positive to 29%. Another strategy, to apply an OGTT to those with an FPG cut point between 5.6 and 6.1 mmol/l, also identifies 29% of the sample as screen positive, although it detects slightly fewer hyperglycemia cases. CONCLUSIONS: Screening strategies based on FPG, complemented by clinical detection rules and/or an OGTT, are effective and practical in the detection of hyperglycemic states meriting clinical intervention.     

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.     

Outline of revision of classification and diagnostic criteria of diabetes mellitus in Japan

Japan Diabetes Society organized a committee for the revision of diagnostic criteria of diabetes mellitus in 1995. Like ADA and WHO reports, this committee adopts a classification based on etiologies, and presents a two-dimensional figure with etiologies and the state of insulin deficiency on different axis. The words IDDM and NIDDM will be retained as terms representing the different degree of insulin deficiency. On the basis of glycemia, diabetic type is defined when fasting plasma glucose exceeded 126 mg/dl and/or 2-hour plasma glucose by 75 g GTT exceeded 200 mg/dl. The diagnosis of diabetes in an individual can be made by confirming sustained diabetic type on repeated tests or co-existance of characteristic clinical features of diabetes. Normal type is defined by FPG < 110 mg/dl and 2hPG < 140 mg/dl. The borderline type, defined as neither normal nor diabetic types, corresponds to IFG plus IGT according to ADA and WHO reports. The application of HbA1c for diagnosis of diabetes and the criteria for gestational diabetes mellitus are also discussed.     

Treating postprandial hyperglycemia does not appear to delay progression of early type 2 diabetes: the Early Diabetes Intervention Program

OBJECTIVE: Postprandial hyperglycemia characterizes early type 2 diabetes. We investigated whether ameliorating postprandial hyperglycemia with acarbose would prevent or delay progression of diabetes, defined as progression to frank fasting hyperglycemia, in subjects with early diabetes (fasting plasma glucose [FPG] <140 mg/dl and 2-h plasma glucose > or =200 mg/dl). RESEARCH DESIGN AND METHODS: Two hundred nineteen subjects with early diabetes were randomly assigned to 100 mg acarbose t.i.d. or identical placebo and followed for 5 years or until they reached the primary outcome (two consecutive quarterly FPG measurements of > or =140 mg/dl). Secondary outcomes included measures of glycemia (meal tolerance tests, HbA(1c), annual oral glucose tolerance tests [OGTTs]), measures of insulin resistance (homeostasis model assessment [HOMA] of insulin resistance and insulin sensitivity index from hyperglycemic clamps), and secondary measures of beta-cell function (HOMA-beta, early- and late-phase insulin secretion, and proinsulin-to-insulin ratio). RESULTS: Acarbose significantly reduced postprandial hyperglycemia. However, there was no difference in the cumulative rate of frank fasting hyperglycemia (29% with acarbose and 34% with placebo; P = 0.65 for survival analysis). There were no significant differences between groups in OGTT values, measures of insulin resistance, or secondary measures of beta-cell function. In a post hoc analysis of subjects with initial FPG <126 mg/dl, acarbose reduced the rate of development of FPG > or =126 mg/dl (27 vs. 50%; P = 0.04). CONCLUSIONS: Ameliorating postprandial hyperglycemia did not appear to delay progression of early type 2 diabetes. Factors other than postprandial hyperglycemia may be greater determinants of progression of diabetes. Alternatively, once FPG exceeds 126 mg/dl, beta-cell failure may no longer be remediable.     

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.     

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     

Identification and treatment of prediabetes to prevent progression to type 2 diabetes

Overt type 2 diabetes is usually preceded by a condition known as prediabetes, which is characterized by impaired fasting glucose (IFG) and impaired glucose tolerance (IGT). Both IFG and IGT exhibit elevated glucose levels that are not sufficient to be classified as diabetes but that represent the development of insulin resistance. Achieving glycemic control in patients with prediabetes through lifestyle and pharmacologic interventions can effectively prevent or delay the development of diabetes and its associated complications. The first step, however, is to identify patients at risk. Although patients can be identified with an oral glucose tolerance test (OGTT) or a fasting plasma glucose (FPG) screening, a normal FPG does not preclude an elevated OGTT and, therefore, the presence of prediabetes. For patients who progress to type 2 diabetes, intensive therapy aimed at reducing and maintaining glycosylated hemoglobin (A1C) levels <7% has been shown to reduce the risk of complications. An A1C level > or =7% should signal the need to initiate or change therapy to achieve glycemic goals.     

Quality of care for patients diagnosed with diabetes at screening

OBJECTIVE: Screening for diabetes has the potential to be an effective intervention, especially if patients have intensive treatment of their newly diagnosed diabetes and comorbid hypertension. We wished to determine the process and quality of diabetes care for patients diagnosed with diabetes by systematic screening. RESEARCH DESIGN AND METHODS: A total of 1,253 users of the Durham Veterans Affairs Medical Center aged 45-64 years who did not report having diabetes were screened for diabetes with an HbA(1c) test. All subjects with an HbA(1c) level > or =6.0% were invited for follow-up blood pressure and fasting plasma glucose (FPG) measurements. A case of unrecognized diabetes was defined as HbA(1c) > or =7.0% or FPG > or =126 mg/dl. For each of the 56 patients for whom we made a new diagnosis of diabetes, we notified the patient's primary care provider of this diagnosis. One year after diagnosis, we reviewed these patients' medical records for traditional diabetes performance measures as well as blood pressure. Follow-up blood pressure was also ascertained from medical record review for all subjects with HbA(1c) > or =6.0% who did not have diabetes. We compared blood pressure changes between patients with and without diabetes. RESULTS: Among patients diagnosed with diabetes at screening, 34 of 53 (64%) had evidence of diet or medical treatment for their diabetes, 42 of 53 (79%) had HbA(1c) measured within the year after diagnosis, 32 of 53 (60%) had cholesterol measured, 25 of 53 (47%) received foot examinations, 29 of 53 (55%) had eye examinations performed by an eye specialist, and 16 of 53 (30%) had any measure of urine protein. The mean blood pressure decline over the year after diagnosis for patients with diabetes was 2.3 mmHg; this decline was similar to that found for 183 patients in the study without diabetes (change in blood pressure, -3.6 mmHg). At baseline, 48% of patients with diabetes had blood pressure <140/90, compared with 40% of patients without diabetes; 1 year later, the same 48% of patients with diabetes had blood pressure <140/90, compared with 56% of patients without diabetes (P = 0.31 for comparing the change in percent in control between groups). CONCLUSIONS: Patients with diabetes diagnosed at screening achieve less tight blood pressure control than similar patients without diabetes. Primary care providers do not appear to manage diabetes diagnosed at screening as intensively as long-standing diabetes and do not improve the management of hypertension given the new diagnosis of 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.     

糖化血红蛋白对糖尿病的诊断价值分析

目的探讨糖化血红蛋白（HbA1c）在糖尿病（DM）诊断中的应用价值。方法 286例健康人和680例DM患者均行口服葡萄糖耐量试验（OGTT）,用特定蛋白分析仪检测HbA1c水平,用BS-420生化分析仪测定血糖,对结果进行分析。结果从健康组到DM组之间的HbA1c的变化关系可看出：DM组患者空腹血糖（FPG）、餐后2h血糖（2hPG）及HbA1c均明显高于健康组（均P〈0.01）,以HbA1c≥6.5%作为DM诊断临界值,其诊断灵敏度为99.18%,诊断特异性为94.45%,均优于以FPG≥7.0mmol/L作为诊断临界值的诊断灵敏度（76.43%）和诊断特异性（89.82%）。结论 HbA1c的值为6.5%时用于诊断DM,与FPG≥7.0mmol/L时联合应用可增加诊断DM的能力。     

Sensory function and albumin excretion according to diagnostic criteria for diabetes

OBJECTIVE: The purpose of this study was to examine sensory function and albumin excretion according to categories of glucose tolerance in individuals undergoing screening for diabetes. RESEARCH DESIGN AND METHODS: Sensory function and albumin excretion measurements were obtained in 636 individuals at the time of screening for diabetes according to American Diabetes Association glucose tolerance criteria. Sensory thresholds were measured by forced-choice techniques. Albumin-to-creatinine ratios were calculated from spot urine samples. RESULTS: Of 90 individuals whose glucose levels were in the range for diabetes, 65 had fasting glucose values >or=126 mg/dl, whereas 25 had 2-h glucose values >or=200 mg/dl, with fasting glucose values <126 mg/dl. In covariance analyses, those with fasting glucose levels >or=126 mg/dl had higher vibration (P < 0.01) and thermal (P < 0.05 for cool and warm) thresholds than those with normal glucose tolerance. This pattern was also evident for albumin-to-creatinine ratios (P < 0.001). In contrast, those with 2-h glucose values >or=200 mg/dl and fasting glucose values <126 mg/dl had sensory threshold and albumin-to-creatinine ratio values similar to those of the normal group. Individuals with fasting glucose levels >or=126 mg/dl had higher vibration threshold and albumin-to-creatinine ratio values (<0.05 and <0.01, respectively) than those with levels <126 mg/dl. CONCLUSIONS: Sensory threshold and albumin excretion values already tend to be greater than normal at screening in individuals with fasting glucose levels >or=126 mg/dl, but not in those with levels <126 mg/dl. A reliance on fasting glucose levels >or=126 mg/dl for screening might not be sufficient for early intervention and the optimal prevention of diabetes complications.     

Predicting the development of diabetes in older adults: the derivation and validation of a prediction rule

OBJECTIVE: To create a simple prediction rule that could perform as well as the 2-h postchallenge plasma glucose (PCPG) test to predict those at risk for diabetes. We created a prediction rule in one sample and prospectively validated it for incident diabetes in a separate cohort. RESEARCH DESIGN AND METHODS: A cross-sectional analysis with data from the Rancho Bernardo Study (age 67 +/- 11 years) to derive a rule predicting abnormal PCPG >/=140 mg/dl, using demographic, clinical, and laboratory data of nondiabetic participants with fasting plasma glucose (FPG) <126 mg/dl. Data from the Health, Aging and Body Composition study (age 74 +/- 3 years) were used to prospectively validate this rule for incident diabetes and compare it with the predictive ability of the PCPG test. RESULTS: Of 1,549 RBS participants, 514 (33%) had PCPG >/=140 mg/dl. Female sex, age, triglycerides, and FPG were most significantly associated with abnormal PCPG. Based on standardized beta-coefficients, we allotted 1 point for female sex, triglycerides >/=150 mg/dl, or FPG 95-104 mg/dl. Age >/=70 years or FPG 105-115 mg/dl were given 2 points, and FPG 116-125 mg/dl received 3 points. In the validation cohort, this simple prediction rule was as good as the 2-h PCPG test for predicting incident diabetes (C-statistic: 0.71 for both). CONCLUSIONS: Advanced age, female sex, FPG, and triglycerides were able to predict adults at risk for diabetes equally well as the 2-h PCPG test. Using this rule, clinicians may better identify older persons who should receive intensive lifestyle intervention to prevent type 2 diabetes.     

American Diabetes Association diabetes diagnostic criteria, advancing age, and cardiovascular disease risk profiles: results from the Third National Health and Nutrition Examination Survey

OBJECTIVE: To evaluate age-specific effects on diabetes prevalence estimates resulting from the American Diabetes Association (ADA) recommendation against use of the oral glucose tolerance test (OGTT), we contrasted the prevalence of two mutually exclusive groups: undiagnosed diabetes according to ADA criteria (no report of diabetes and fasting glucose [FG] > or =126 mg/dl) and isolated postchallenge hyperglycemia (IPH) (FG <126 mg/dl and OGTT > or =200 mg/dl), a group designated to have diabetes by World Health Organization (WHO) criteria but not ADA criteria. RESEARCH DESIGN AND METHODS: The weighted age-specific ratios of undiagnosed diabetes:IPH were calculated for 2,844 subjects aged 40-74 years without reported diabetes who had both FG and OGTT. A ratio > 1.0 indicated that the proportion of undiagnosed diabetes was greater than that of IPH. Mean levels of HbA1c and cardiovascular disease (CVD) risk factors were contrasted among people with undiagnosed diabetes and IPH and those without either abnormality ("nondiabetic"). RESULTS: Both undiagnosed diabetes and IPH increased with age, but age-specific undiagnosed diabetes:IPH ratios decreased from 5.49 in the 40-44 age-group to 0.77 in the 70-74 age-group. Regression analysis showed a significant (P = 0.006) negative association between age and these ratios. Mean HbA1c was 7.1% in the undiagnosed diabetes group and differed significantly from that of the IPH and nondiabetic groups (5.6 and 5.3%, respectively). Individuals with undiagnosed diabetes had less favorable triglycerides, BMI, and HDL cholesterol compared with people with IPH. CONCLUSIONS: Compared with WHO criteria, the ADA criteria underestimate glucose abnormalities more with increasing age. However, compared to those with undiagnosed diabetes, individuals with IPH had a mean HbA1c level that is considered in the nondiabetic range, and this group had significantly more favorable levels of several key CVD risk factors. These findings suggest that the ADA criteria, although underestimating the abnormalities of postchallenge hyperglycemia that occur frequently with increasing age, appear to be effective at identifying a group of individuals with both unfavorable CVD risk factor profiles and evidence of long-term exposure to hyperglycemia.     

Dose-response effect of pioglitazone on insulin sensitivity and insulin secretion in type 2 diabetes

OBJECTIVE: To investigate the dose-response effects of pioglitazone on glycemic control, insulin sensitivity, and insulin secretion in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: A total of 58 diet-treated patients with type 2 diabetes (aged 54 +/- 1 years; 34 men and 24 women; BMI 31.5 +/- 0.6 kg/m(2)) were randomly assigned to receive placebo (n=11) or 7.5 mg (n=13), 15 mg (n=12), 30 mg (n=11), or 45 mg (n=11) of pioglitazone per day for 26 weeks. Before and after 26 weeks, subjects underwent a 75-g oral glucose tolerance test (OGTT). RESULTS: Patients treated with 7.5 or 15 mg/day of pioglitazone had no change in fasting plasma glucose (FPG) and fasting plasma insulin (FPI) concentrations or in plasma glucose (PG) and insulin concentrations during the OGTT. Patients treated with 30 and 45 mg/day of pioglitazone, respectively, had significant decreases from placebo in HbA1c (delta=-2.0 and -2.9%), FPG (delta=-66 and -97 mg/dl), and mean PG during OGTT (delta=-84 and -107 mg/dl). Fasting plasma insulin decreased significantly in the 45-mg/day pioglitazone group, but the mean plasma insulin during the OGTT did not change. The insulinogenic index (delta area under the curve [AUC] insulin/deltaAUC glucose) during the OGTT increased significantly in the 30- and 45-mg/day pioglitazone groups (0.13 +/- 0.03 to 0.27 +/- 0.05, P < 0.05). From the OGTT, we previously have derived a composite whole-body insulin sensitivity index (ISI) that correlates well with that measured directly with the insulin clamp technique. Whole-body ISI [ISI=10,000/(square-root (FPG x FPI) x (PG x PI)) where PG and PI equal mean plasma glucose and insulin concentrations during OGTT] increased significantly in patients treated with 30 mg (1.8 +/- 0.3 to 2.5 +/- 0.3, P < 0.05) or 45 mg (1.6 +/- 0.2 to 2.7 +/- 0.6, P < 0.05) per day of pioglitazone. In the basal state, the hepatic ISI [k/(FPG x FPI)[k/(FPG x FPI)], which agrees closely with that measured directly with tritiated glucose, increased in patients treated with 30 mg (0.13 +/- 0.02 to 0.21 +/- 0.03, P < 0.05) and 45 mg (0.11 +/- 0.02 to 0.24 +/- 0.06, P < 0.05) per day of pioglitazone. Significant correlations between the dose of pioglitazone and the changes in HbA1c (r=-0.58), FPG (r=-0.47), mean PG during the OGTT (r=-0.46), insulinogenic index (r=0.34), hepatic ISI (r=0.44), and whole-body ISI (r=0.36) were observed. CONCLUSIONS: Pioglitazone improves glycemic control through the dose-dependent enhancement of beta-cell function and improved whole-body and hepatic insulin sensitivity.