Diagnostic criteria for diabetes mellitus

In the last three years, new diagnostic criteria for diabetes mellitus have been proposed by the American Diabetes Association (ADA, 1997), the World Health Organization (WHO) consultation (1998), and the Japan Diabetes Society (JDS, 1999). The most important change from the previous WHO criteria (1985) to these criteria is a decrease in fasting plasma glucose level (FPG) from 140 mg/dl to 126 mg/dl, which defines diabetes mellitus. These criteria attach more importance to FPG than to plasma glucose levels 2 hours after 75 g glucose load (2 hPG). According to these criteria, for example, in one instance with FPG > or = 126 mg/dl, the diagnosis of diabetes mellitus is warranted, if the postprandial plasma glucose > or = 200 mg/dl or another FPG > or = 126 mg/dl were reconfirmed on a subsequent day. The ADA criteria did not recommend an oral glucose tolerance test (OGTT) for routine clinical use. These criteria has established a new category of impaired fasting glucose (IFG) (> or = 110 mg/dl and 126 < mg/dl), similar to impaired glucose tolerance (IGT) which is recognized by performing OGTT. We have reported from a cohort study that there was only one risk factor for IGF: worsening of metabolic derangement progressing to overt diabetes. With IGT, however, there are two risks: a risk for progression to diabetes, and a risk for development of cardiovascular disease. Therefore it seems that whether or not OGTT should be performed depends on the purpose: simply diagnosing for overt diabetes, or detecting risk factors for cardiovascular disease. The JDS criteria proposed the use of HbA1C as a supporting diagnostic tool, because JDS has achieved a fruitful standardization in Japan to a considerable extent. According to the JDS criteria, a diagnosis of diabetes mellitus can be made by an FPG > or = 126 mg/dl when HbA1C > or = 6.5% is confirmed. It is expected that these new criteria will promote further efforts against the increasing number of patients with diabetes mellitus.     

Differences in metabolic parameters and cardiovascular risk between American Diabetes Association and World Health Organization definition of impaired fasting glucose in European Caucasian subjects: a cross-sectional study

Introduction

The American Diabetes Association (ADA) defines impaired fasting glucose (IFG) as fasting plasma glucose concentration of 100–125 mg/dl, whereas the World Health Organization (WHO) and the International Diabetes Federation (IDF) define IFG as fasting plasma glucose levels of 110–125 mg/dl. We identified differences in metabolic parameters and cardiovascular disease (CVD) risk according to the ADA or WHO/IDF definition of IFG.

Material and methods

Healthy drug-naive Caucasian (Greek) subjects (n = 396; age 55 ±12 years) participated in this cross-sectional study.

Results

Diastolic blood pressure (DBP) and uric acid levels were higher in the subjects with glucose 100–109 mg/dl compared with those with glucose < 100 mg/dl (87 ±9 mm Hg vs. 84 ±11 mm Hg, p = 0.004 for DBP, 5.6 ±1.5 mg/dl vs. 5.0 ±1.0 mg/dl, p = 0.002 for uric acid), whereas triglyceride levels were lower in subjects with glucose 100–109 mg/dl compared with those with glucose ≥ 110 mg/dl (169 mg/dl (interquartile range (IQR) = 102–186) vs. 186 mg/dl (IQR = 115–242), p = 0.002). Only the ADA definition recognized subjects with significantly increased 10-year CVD risk estimation (SCORE risk calculation) compared with their respective controls (5.4% (IQR = 0.9–7.3) vs. 4.1% (IQR = 0.7–5.8), p = 0.002).

Conclusions

The ADA IFG definition recognized more subjects with significantly increased CVD risk (SCORE model) compared with the WHO/IDF definition.     

Conduite à tenir devant une glycémie « limite supérieure »

Type 2 diabetes is preceded by a long preclinical period with progressively glucose tolerance abnormalities. Beside diabetes defined by a venous fasting glucose superior to 7 mmol/l (1.26 g/l), American Diabetes Association identified two others abnormalities of glucose tolerance: the impaired glucose tolerance (IGT) defined by a two hours glycaemia between 7.8 and 11 mmol/l (1.4 and 1.9 g/l) at the oral glucose tolerance test (OGTT) and the impaired fasting glycaemia (IFG) with a fasting glycaemia between 6.1 and 6.9 mmol/L (1.1 and 1.25 g/l). Prevalence of IGF is between 2 and 10% in non diabetic adult subjects. IFG concerns mainly subjects aged 40–50 years and is 1.5 to 3 fold more frequent in man. Most of the well-known risk factors for developing type 2 such us overweight, abdominal obesity, familial history of diabetes, over –consumption of fat and alcohol are present in subjects having IFG. Hypertension is present in more than 50% of the subjects with IFG. Fifty percents of subjects with IFG are also an impaired glucose tolerance. IFG is associated with a high diabetes risk because 10 to 30% of subjects with IFG will develop type 2 diabetes after five years. Both IFG and IGT are associated with an increase of risk of cardiovascular mortality while the two hours glycaemia of OGTT is more predictive than IFG. Microalbuminuria and carotid intima media-thickness are significantly increased in subjects having both IGT and IFG compared to subjects with only IGT. Subjects with IFG are associated with an increase risk of developing diabetes and cardiovascular disease. IFG requires the realization of an OGTT to search IGT or diabetes.     

Clinical screening examination for impaired glucose tolerance: is it possible to diagnose impaired glucose tolerance without a 75g oral glucose tolerance test?

It is well known that diabetes mellitus is one of the most crucial risk factors in the pathogenesis of atherosclerosis, including cardiovascular diseases (CVD). Considerable epidemiological and clinical studies, such as the Funagata study and the Diabetes Epidemiology Collaborative analysis of Diagnostic criteria in Europe (DECODE) study, have established that even a prediabetic state, including impaired glucose tolerance (IGT), is strongly associated with the occurrence of CVD. For the diagnosis of IGT, the 75g oral glucose tolerance test (75g OGTT) is required clinically, but the test takes at least 2 hours, at considerable cost. Therefore, for the prevention of atherosclerosis and subsequent CVD, another methods and/or beneficial parameters are anticipated to diagnose IGT without 75g OGTT. Recent studies have suggested that subjects beyond approximately 100 mg/dl fasting plasma glucose (FPG) might be classified into IGT by using receiver operating characteristic (ROC) analyses, and that the FPG 100 mg/dl is a suitable cut-off level between IGT and normal glucose tolerance (NGT). In contrast, although it is difficult to distinguish IGT from NGT by the HbAlc level alone, the combination of FPG with HbAlc is more beneficial for the diagnosis of IGT.     

Should we consider performing oral glucose tolerance tests more frequently in postmenopausal women for optimal screening of impaired glucose tolerance?

OBJECTIVE: To investigate an optimal screening protocol for impaired glucose tolerance (IGT) and type II or non-insulin-dependent diabetes mellitus (DM) by using fasting plasma glucose (FPG) and oral glucose tolerance test (OGTT) in postmenopausal women. DESIGN: One hundred consecutive postmenopausal women were screened with FPG determination, and then all underwent an OGTT. Basal serum lipid and insulin levels of these women were also determined. Insulin sensitivity was determined by using the homeostasis model assessment. Receiver operating characteristic analysis was performed to determine the efficacy of these variables in detecting women with IGT and DM, and optimal cutoff values were determined. RESULTS: FPG with a cutoff value of 98 mg/dL had the best combination of sensitivity (71%) and specificity (76%) for the detection of IGT and DM. Combined FPG and body mass index screening (with the optimal cutoff value of 26.5 kg/m2) improved the sensitivity to 96% but decreased the specificity to 47%. This combined screening protocol detected 94% of the women with IGT and all diabetic women. CONCLUSIONS: Given that IGT and DM are common among postmenopausal women and DM can be prevented by nonpharmacologic interventions in women with IGT, OGTT may be used more frequently among these women. Our data indicate that for optimal screening of non-insulin-dependent DM and IGT, OGTT should be considered in postmenopausal women, especially when risk factors in addition to age are present. This model may detect most of the women with IGT and almost all diabetic women.     

糖化血红蛋白在糖代谢异常患者中的改变及其与血糖的关系

目的探讨糖化血红蛋白（HbAlc）检测在不同糖代谢异常状态的临床价值。方法选取254名受试者（其中男149人,女105人）进行口服糖耐量试验（OGYr）和HbAlc检测。根据OGTY结果分为正常糖耐量（NGT）、单纯空腹血糖受损（I-IFG））、单纯糖耐量受损（I-IGT）、IFG合并IGT（IFG／IGT）和糖尿病（DM）5组,通过单因素方差分析比较各组HbAlc值,对各组HbAlc与空腹血糖（FPG）和OGTr2h血糖（2hPG）进行线性相关和回归分析。结果①HbAlc水平（％,下同）DM组（7．41±1．94）明显高于其余4组（以上P均〈0．01）,I-IFG组（6．06±0．37）、I-IGT组（5．91±0．39）、IFG／IGT组（6．12±0．38）3组间差异无统计学意义（P〉0．05）,但分别明显高于NGT组（P〈0．05）。②DM组HbAlc分别与FPG（r=0．934,P〈0．01）和2hPG（r=0．760,P〈0．01）存在着明显的正相关,回归方程为：HbAlc=2．957＋0．458（FPG）＋0．05（2hPG）;IFG／IGT组（r=0．326,P〈0．01）、I-IGT组（r=0．254,P〈0．05）HbAlc只与2hPG存在正相关;I-IFG组HbAlc只与FPG存在正相关（r=0．404,P〈0．01）;NGT组HbAlc与FPG（r=0．157）和2hPG（r=-0．006）均不存在相关性。结论糖化血红蛋白水平能够正确地反映正常糖代谢、糖调节受损和糖尿病3种不同糖代谢状态的血糖水平,是区分3种糖代谢状态的有用指标。     

Body mass index and waist circumference according to glucose tolerance status in Korea: the 2005 Korean Health and Nutrition Examination Survey

The purpose of this study was to investigate the stage of glucose intolerance in which persons showed a maximum obesity in Korea. A total of 4,479 participants, who were involved in the 2005 Korean National Health and Nutrition Examination Survey, was examined. The participants were divided into 5 groups by fasting plasma glucose (FPG); normal fasting glucose (NFG)1, FPG < 90 mg/dL; NFG2, FPG 90-99 mg/dL; impaired fasting glucose (IFG)1, FPG 100-109 mg/dL; IFG2, FPG 110-125 mg/dL; and diabetes mellitus, FPG ≥ 126 mg/dL or with anti-diabetes drugs. In those with FPG < 110 mg/dL, body mass index (BMI) and waist circumference (WC) were increased with increase of FPG (BMI in men; NFG1, 23.3 ± 0.1; NFG2, 24.4 ± 0.1; IFG1, 25.0 ± 0.2 kg/m(2), in women; NFG1, 23.0 ± 0.1; NFG2, 24.0 ± 0.1; IFG1, 24.8 ± 0.2 kg/m(2), WC in men; NFG1, 82.1 ± 0.3; NFG2, 85.3 ± 0.3; IFG1, 86.7 ± 0.5 cm, in women; NFG1, 77.1 ± 0.2; NFG2, 79.4 ± 0.3; IFG1, 81.8 ± 0.6 cm). In IFG2 and diabetes range, there was no more increase of BMI and WC with increase of FPG in each sex. The data suggest that degree of obesity increases with an increase of FPG in range of FPG < 100 mg/dL, peaked in FPG of 100-109 mg/dL, and then plateaus in higher FPG range in general Korean population.     

Impaired Secretion of Total Glucagon-like Peptide-1 in People with Impaired Fasting Glucose Combined Impaired Glucose Tolerance

Objective: We assessed the serum glucagon-like peptide-1 (GLP-1) levels for Chinese adults with pre-diabetes (PD) and newly-diagnosed diabetes mellitus (NDDM) during oral glucose tolerance test (OGTT). The relationships between total GLP-1 level and islet β cell function, insulin resistance (IR) and insulin sensitivity (IS) were also investigated.Methods: A 75g glucose OGTT was given to 531 subjects. Based on the results, they were divided into groups of normal glucose tolerance (NGT), isolated impaired fasting glucose (IFG), isolated impaired glucose tolerance (IGT), IFG combined IGT (IFG+IGT) and NDDM. Total GLP-1 levels were measured at 0- and 2-hour during OGTT. Homeostasis model assessment of β cell function (HOMA-β), HOMA of insulin resistance (HOMA-IR), Gutt and Matsuda indexes were calculated. The relationships between GLP-1 level and β cell function, IR and IS were analyzed.Results: The levels of total fasting GLP-1 (FGLP-1), 2h GLP-1 (2hGLP-1) and 2hGLP-1 increments (∆GLP-1) following OGTT reduced significantly in IFG+IGT and NDDM groups (P<0.005). HOMA-β , HOMA-IR, Gutt and Matsuda indexes demonstrated various patterns among NGT, isolated IFG, isolated IGT, IFG+IGT and NDDM groups (P<0.05). Spearman rank correlation analysis and multivariable linear regression model suggested that some levels of correlation between GLP-1 levels, ∆GLP-1 and β cell function, IR (P<0.05).Conclusions: The total GLP-1 levels and its response to glucose load decreased significantly in IFG+IGT group, compared to isolated IFG or IGT group. They were even similar to that of NDDM group. Moreover, there were observable correlations between impaired GLP-1 secretion and β cell function, IR and IS.     

Gestational diabetes mellitus

Gestational diabetes (GDM) is defined as any degree of glucose intolerance with onset or first recognition during pregnancy and is associated with increased feto-maternal morbidity as well as long-term complications in mothers and offspring. GDM is diagnosed by an oral glucose tolerance test (OGTT) or fasting glucose concentrations in the diabetic range. In case of a high risk for GDM/type 2 diabetes (history of GDM or prediabetes [impaired fasting glucose or impaired glucose tolerance]; malformation, stillbirth, successive abortions or birth-weight > 4500 g in previous pregnancies) performance of the OGTT (120 min; 75 g glucose) is recommended already in the first trimester and--if normal--the OGTT should be repeated in the second/third trimester. In case of clinical symptoms of diabetes (glucosuria, macrosomia) the test has to be performed immediately. All other women should undergo a diagnostic test between 24 and 28 gestational weeks. If fasting plasma glucose exceeds 95 mg/dl, 1 h 180 mg/dl and 2 hrs 155 mg/dl after glucose loading (OGTT) the woman is classified as GDM (one pathological value is sufficient). In this case a strict metabolic control is mandatory. All women should receive nutritional counseling and be instructed in blood glucose self-monitoring. If blood glucose levels cannot be maintained in the normal range (fasting < 95 mg/dl and 1 h after meals < 130 mg/dl) insulin therapy should be initiated. Maternal and fetal monitoring is required in order to minimize maternal and fetal/neonatal morbidity and perinatal mortality. After delivery all women with GDM have to be reevaluated as to their glucose tolerance by a 75 g OGTT (WHO criteria).     

The effect of lowering the threshold for diagnosis of impaired fasting glucose

PURPOSE: The aim of this study was to evaluate the effect of lowering the fasting plasma glucose (FPG) criteria for impaired fasting glucose (IFG) on the prevalence of IFG and the risk for the development of diabetes associated with IFG in Koreans. MATERIALS AND METHODS: A total of 7,211 subjects who had normal glucose tolerance (NGT) or IFG were recruited. Subjects were evaluated at baseline and after two years follow up. Clinical data including total cholesterol, FPG and blood pressure were examined. RESULTS: Lowering the criteria for IFG from 6.1 mmol/L (110 mg/dL) to 5.6 mmol/L (100 mg/dL) increased the prevalence of IFG from 6.6% (494 subjects) to 24.4% (1829 subjects). After the 2 years follow up period, 91 subjects (1.3%) developed diabetes. Twenty one (0.3%) subjects developed diabetes among 5,382 NGT subjects and 70 (3.8%) subjects developed diabetes among 1,829 IFG (5.6-7.0 mmol/L) subjects. Lowering the IFG threshold from 6.1 mmol/L to 5.6 mmol/L resulted in a 18.4% decrease in specificity and 23.9% increase in sensitivity for predicting diabetes. The baseline FPG for predicting the development of diabetes after 2 years at a point on the receiver operating characteristic curve that was closest to the ideal 100% sensitivity and 100% specificity was 5.7 mmol/L (103 mg/dL). CONCLUSION: Lowering the FPG criterion of IFG should have benefits in predicting new onset type 2 diabetes mellitus in Koreans. The economic and health benefits of applying the new IFG criteria should be evaluated in future studies.     

多囊卵巢综合征患者的糖代谢特点分析

目的 研究多囊卵巢综合征（PCOS）患者的糖代谢特征。方法 选择2014年1月~2018年3月我院收治的符合鹿特丹标准、未经治疗的PCOS患者935例,测定身高、体重,并行口服葡萄糖耐量试验（OGTT）和胰岛素释放试验（IRT）,计算体重指数（BMI）、胰岛素抵抗稳态指数模型（HOMA-IR）、β细胞功能指数（HOMA-β）等参数。根据血糖水平将 PCOS 患者分为糖代谢正常（NGT）组、空腹血糖受损（IFG）组、糖耐量受损（IGT）组、混合型糖耐量受损（CGI）组及糖尿病（T2DM）组;根据体重指数     

Revising the fasting glucose threshold for detection of cardiovascular risk factors: analysing two representative population-based studies of more than 50 000 Iranians in 3 years: The National Survey of Risk Factors for Non-Communicable Diseases of Iran

Objectives: To study the prevalence of cardiovascular risk factors across different glycaemia strata and to assess the optimal cut-off value of fasting plasma glucose (FPG) to identify the constellation of cardiovascular risk factors.

Methods: Data of the National Survey of Risk Factors for Non-Communicable Diseases of Iran (SURFNCD 2005–2007) were analysed. Prevalence rates of obesity, central obesity, hypertension and hypercholesterolemia of individuals with Impaired Fasting Glucose (IFG) were compared with those of individuals with normal fasting glycaemia and newly diagnosed diabetes. Optimal FPG cut-point to diagnose subjects with cardiovascular risk factors was assessed.

Results: Prevalence of each and combinations of cardiovascular risk factors were higher among subjects with IFG compared to those with normal fasting glycaemia. The areas under the curve (AUC) for detecting cardiovascular risk were highest at FPG values of 90?mg/dL. FPG of 90?mg/dL was the optimal cut-off and, in comparison to 100?mg/dL, corresponds to correct detection of 26–29% of obese, 22–27% of centrally obese, 26–29% of hypertensive and 25–30% of hypercholesterolemic individuals.

Conclusions: IFG and even lower levels of FPG are associated with high prevalence of cardiovascular risk factors in Iranian adults. This study suggests the FPG cut-off to be revised at 90?mg/dL to identify people with increased cardiovascular risk.     

Laboratory diagnosis and monitoring of diabetes mellitus.

The American Diabetes Association emphasizes fasting plasma glucose (FPG) levels, rather than the oral glucose tolerance test (OGTT), to diagnose diabetes mellitus. The diagnostic cutoff for FPG is 126 mg/dL (7.0 mmol/L). A 2-hour plasma glucose level of 200 mg/dL (11.1 mmol/L) or more during an OGTT or a random plasma glucose level of 200 mg/dL (11.1 mmol/L) or more also is diagnostic of diabetes. The 100-g, 3-hour OGTT remains the "gold standard" for gestational diabetes mellitus (GDM). Two of 4 samples exceeding cutoffs (fasting, > or = 105 mg/dL [5.8 mmol/L]; 1 hour, > or = 190 mg/dL [10.5 mmol/L]; 2 hours, > or = 165 mg/dL [9.2 mmol/L]; 3 hours, > or = 145 mg/dL [8.0 mmol/L]) indicate GDM. An effective GDM screening test is plasma glucose 1 hour after a 50-g oral glucose load. Tight control, which requires self-monitoring of blood glucose, reduces microvascular complications for patients with type 1 or type 2 diabetes. Patients with well-controlled diabetes have glycohemoglobin concentrations of 7% AIc (0.07 AIc/A) or less. Microalbuminuria indicates early, reversible, diabetic nephropathy. The random urine albumin-creatinine ratio is a convenient effective screening test. Albumin-creatinine ratios in the 0.03 to 0.30 (g/g) range indicate microalbuminuria.     

Comparison of area under the curve in various models of diabetic rats receiving chronic medication

IntroductionThe oral glucose tolerance test (OGTT) is widely used as a diagnostic tool for impaired glucose tolerance (IGT) in clinical settings and animal experiments. The area under the curve (AUC) is then developed to quantify the total increase in blood glucose during the OGTT. Similarly, attenuation of the increased AUC indicates the improvement of IGT in animals. Variations in fasting plasma glucose between individuals stimulate the development of incremental area under the curve (iAUC). However, the iAUC determined from subtracting the baseline value of fasting plasma glucose (similar to ΔAUC) has been challenged as problematic without evidence.Material and methodsWe developed four different diabetic animal models. In each model, rats were treated with metformin, dapagliflozin, and insulin respectively for 1 week. OGTTs were performed after 7 days of the drug treatment. The acute blood glucose changes induced by one-time treatment of drugs were also compared.ResultsAfter a daily application of each drug at an effective dose for 7 days, results indicated potency in the following order: insulin > dapagliflozin > metformin. This was determined by calculation using the AUC in all diabetic models. However, the order changed when using the calculation with iAUC. Additionally, signals were changed before the OGTT in each model that received repeated treatment of each drug. Notably, drug potency was shown to be the same in OGTT calculated from iAUC and AUC in diabetic rats receiving acute treatment.ConclusionsiAUC seems unsuitable for application in cases where subjects are receiving chronic medication(s).     

The impaired hyperglycemic peak as an additional indicator of Type 2 diabetes development is misdetected

Because there is not an optimal control for Type 2 diabetes mellitus (DM2), which encompasses about 90% of diagnosed diabetic patients, its prevention is key. Early detection of DM2 development can be made through impaired fasting glucose and/or impaired glucose tolerance diagnosis. However, cases exist when oral glucose tolerance test (OGTT) results show an hyperglycemic peak >or =200 mg/dl as a unique alteration. This alteration is defined as impaired hyperglycemic peak (IHP) and should be considered as an additional early indicator of DM2 development. Because IHP is commonly misdetected by the standard OGTT, it is proposed that this misdetection can be solved using a closer sampled OGTT. The objective of this research was to detect IHP on 225 volunteers using a 10 min sampled OGTT during 2 h. Results show the existence of IHP in 25 cases, making it the most frequent and the less detected OGTT alteration. In eight of these cases, IHP could not have been detected using a standard OGTT, because at 30, 60 and 90 min, plasma glucose concentrations were <200 200 mg/dl, however, at 40, 50, 70, and/or 80 min, IHP exists.     

空腹血糖受损患者脂联素水平的临床观察

目的探讨空腹血糖受损（IFG）患者脂联素水平的变化。方法入选糖耐量正常（NGT）、孤立性空腹血糖受损（I-IFG）、孤立性糖耐量低减（I-IGT）、空腹血糖受损并糖耐量低减（IFG／IGT）、新发2型糖尿病（T2DM）各30例，采用酶联免疫吸附法（ELISA）测定血清脂联素，同时检测胰岛素水平及血糖、血脂，计算胰岛素抵抗指数（HOMA．IR）。结果I-IFG组、1-IGT组、IFG／IGT组及新发T2DM组脂联素均明显低于NGT组（P均〈0．01）；新发T2DM组和IFG／IGT组的HOMA-IR均〉I-IGT组〉I-IFG组〉NGT组，各组间差异有统计学意义（P均〈0．05或P〈0．01）；脂联素与空腹血糖（FBG）、餐后2h血糖（2HBG）及HOMA-IR呈负相关（Pa〈0．01）。结论在I-IFG阶段已存在脂联素水平降低，胰岛素抵抗增加，具有向糖尿病转化及并发大血管病变的风险，提高脂联素水平可为糖尿病及其并发症的防治提供一条新的思路。     

The usefulness of glycated hemoglobin A1c (HbA1c) for identifying dysglycemic states in individuals without previously diagnosed diabetes

PurposeWe investigated HbA1c's validity as a screening parameter for excluding dysglycemic states in the studied population.Material/MethodsSensitivity and specificity of HbA1c in some cut-off points were compared with diagnoses based on the oral glucose tolerance test (OGTT) in individuals diagnosed between 2009–2010. Receiver operating characteristic (ROC) analysis for HbA1c was conducted. HbA1c and OGGT measures were done in 441 people (253 women, 187 men, average age 40.1 years (18–79 years)). Based on the OGGT test 37 individuals were diagnosed as diabetic, 28 as impaired glucose tolerant (IGT) and 63 as having impaired fasting glycemia (IFG).ResultsA cut-off value of 6.5% HbA1c classifies diabetic subjects with a sensitivity of 45.9% and specificity of 97.5%. In the investigated population the best cut-off point (the highest sum of the sensitivity and specificity) was 5.9% HbA1c (sensitivity 86.6%, specificity 73%). HbA1c values excluding the risk of dysglycemic states have shown false negative rate in 31.9% when HbA1c was 5.5% and 10.6% when HbA1c was 5.0%.ConclusionsOur results indicate that in the investigated population the evaluation of the prevalence of type 2 diabetes using HbA1c values proposed by the American Diabetes Association (ADA) has unsatisfactory sensitivity and detects less than a half of cases of diabetes based on the OGTT diagnoses. HbA1c 5.7% does not have sufficient specificity to identify individuals not being at risk of any disorder of glucose metabolism.     

Hemoglobin A1c testing alone does not sufficiently identify patients with prediabetes

Whether hemoglobin A(1c) (HbA(1c)) values are suitable for diagnosing diabetes has been debated. We sought to assess the prevalence of elevated HbA(1c) levels in a prediabetes patient population. Oral glucose tolerance tests and HbA(1c) levels were analyzed for patients entering a diabetes prevention program between January 1, 2007, and September 13, 2009. We calculated the percentage of patients with impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) who had HbA(1c) values in the 6.0% to 6.4% range or in the 5.7% to 6.4% range. The mean age of the 242 patients was 62 years; 64.0% were women, and 88.0% were white. Isolated IFG was detected in about 56.2% of patients and combined IFG and IGT in about 37.2%. Only 28.5% of patients had HbA(1c) values in the 6.0% to 6.4% range, whereas 65.3% had values in the 5.7% to 6.4% range. Our data suggest that reliance on HbA(1c) testing alone to identify candidates for a diabetes prevention program would miss a substantial number of eligible patients.     

Cell-Mediated Immunity in Diabetes Mellitus

Cell-mediated immunity was evaluated in patients with diabetes mellitus by delayed hypersensitivity skin tests and in vitro lymphocyte transformations. Only 44% of diabetic patients had skin test reactivity to Candida antigen, compared with 88% of normal controls (P < 0.001). Insulin-dependent diabetic (IDD) patients had abnormally low lymphocyte transformation responses to phytohemagglutinin, concanavalin A, and streptokinase-streptodornase (P < 0.05). This defect was not corrected by culturing the cells in nondiabetic plasma. IDD patients with persistent hyperglycemia (fasting serum glucose level, >200 mg/dl) had lower levels of transformation than did IDD patients with fasting serum glucose levels less than 150 mg/dl. Lymphocytes from two IDD patients with poor lymphocyte transformation responses had marked improvement in response to phytohemagglutinin when the lymphocytes were cultured after a preincubation period designed to deplete cultures of suppressor activity. Seven IDD patients were studied serially over 12 months. Lymphocyte transformation responses in four of these patients improved coincidentally with a change in the level of fasting hyperglycemia from >200 to <150 mg/dl. The other three IDD patients with consistent fasting serum glucose levels of >200 mg/dl had poor lymphocyte transformation responses. Diabetic patients have demonstrable defects in lymphocyte function which improved in a small number of patients with reduction in the level of fasting hyperglycemia.     

Adipocyte factors,high-sensitive C-reactive protein levels and lipoxidative stress products in overweight postmenopausal women with normal and impaired OGTT

Objective

In obese postmenopausal women we assessed leptin and adiponectin, high-sensitive C-reactive protein (hsCRP), serum lipids and lipoxidative stress products: oxidized LDL (oxLDL) and malondialdehyde (MDA), in relation to impaired glucose tolerance (IGT).

Methods

Thirty-eight overweight/obese postmenopausal women were included in the study. Eighteen with normal glucose metabolism (NGT) and twenty with IGT, as it is diagnosed by OGTT. Serum leptin, adiponectin, hsCRP and MDA were measured at time 0 and 120 min of OGTT while total-cholesterol, LDL, HDL, triglycerides, oxLDL and anti-oxLDL autoantibodies at time 0. Insulin resistance (HOMA)/sensitivity (QUICKI) indexes were estimated.

Results

In subjects with NGT, hsCRP was positively correlated with fasting leptin and HOMA, while in subjects with IGT negatively with QUICKI. In both groups, hsCRP was positively correlated with fasting insulin, body mass index and waist circumference. Fasting adiponectin was positively associated with HDL in both groups and negatively with triglycerides in subjects with NGT as well as with serum glucose levels at time 120 min of OGTT in subjects with IGT. No association was observed between oxLDL and adipokines. A significant positive association was found between oxLDL and HOMA in subjects with IGT. During OGTT there was a significant increase of leptin and MDA levels in both groups.

Conclusions

A relationship exists between obesity, insulin and sub-clinical inflammation. Leptin and lipid peroxidation are linked to hyperglycaemic state while oxLDL might be considered as a predictor of insulin resistance. Adiponectin could exert its antiatherogenic effect through HDL independently of the presence of IGT.