Unconscious Racial Bias May Affect Dentists' Clinical Decisions on Tooth Restorability: A Randomized Clinical Trial.

METHODS: In this single-center cross-sectional survey, 57 dentists were given a clinical scenario in combination with a patient's relevant clinical photographs and radiographs depicting either a Black or White patient presenting with a decayed tooth and associated symptoms of irreversible pulpitis. Explicit bias was measured through a questionnaire, which evaluated participants' course of treatment, strength of recommendation, and their perception of patients' dental cooperativeness. Implicit bias was evaluated through brief implicit associate tests. RESULTS: Recommendation for root canal treatment (RCT) in the White patient condition was significantly higher than in the Black patient condition (χ2 = 4.77, P < 0.05). Overall, participants were significantly more likely to recommend root canal treatment to White patients (t = 2.46, P = 0.0172) and significantly more likely to recommend extraction for Black patients (t = 3.03, P = 0.0034). In total, 91.23% and 78.95% of all participants displayed high Brief Implicit Association Test race and cooperation scores, respectively, showing a pro-White bias in both categories. This trend was shown to be irrespective of the patient condition. CONCLUSIONS: Dentists' decision making was affected by the race of the patient, resulting in a greater likelihood of extractions (less RCT) for Black patients presenting with a broken-down tooth and symptoms of irreversible pulpitis. KNOWLEDGE TRANSFER STATEMENT: The results of this study can be used by clinicians to understand the impact that unconscious racial bias may have on their treatment planning decisions. This information can create awareness, thereby reducing the impact that potential biases can have on the treatment patients receive.

Different distribution of phenotypes and glucose tolerance categories associated with two alternative proposed cutoffs of insulin resistance.

We investigated whether two alternative HOMA-IR thresholds recently proposed identify similar phenotype and have the same impact on gluco-metabolic risk. The two IR cutoffs, IR1 and IR2 (IR1: HOMA-IR >5.9 and IR2: HOMA-IR between 2.8 and 5.9 with HDL-C <51 mg/dl), were applied to a database of 2,360 outpatients, and their association with phenotypes, glucose tolerance, lipids and metabolic syndrome (MetS) was examined. IR1 group showed 5.5% of overweight versus 27.8% of IR2 subjects, and obesity was present in 92.3 versus 68.4%, respectively. We observed the major prevalence of pathological waist in IR1 compared to IR2 subjects: 96.0 versus 80.5% (p < 0.001). After OGTT, IR1 patients presented higher prevalence of impaired glucose tolerance (IGT: 25.8 vs. 20.2%, p < 0.001) and DM2 was diagnosed in 39.7% of IR1 versus 11.3% of IR2 patients (p < 0.001) with odds ratio (OR) 8.3 (95% CI 6.1-11.6) versus 0.8 (0.6-1.2), respectively. IR1 versus IR2 cutpoint showed higher significant (mean ± SEM) total cholesterol (224.8 ± 2.6 vs. 213.1 ± 1.7 mg/dl, p < 0.001) and triglyceride (208.1 ± 12.3 vs. 177.4 ± 4.8 mg/dl, p < 0.001) levels. MetS prevalence was significantly higher in IR1 than IR2 (89.0 vs. 78.3%, p < 0.001). The IR1 cutpoint was associated with a higher OR of MetS 7.3 (5.3-10.2) versus 5.2 (2.8-9.5) of IR2. In summary, the two alternative HOMA-IR cutoffs identify subjects with different distribution of phenotypes and gluco-metabolic risk. The IR1 patients are characterized by higher prevalence of obesity, pathological waist, MetS, dyslipidemia and IGT/DM2.

Effects of antihypertensive treatments on incidence of diabetes: a case-control study.

AIMS: Aim of this case-control study is the assessment of the relationship between antihypertensive treatment and incidence of diabetes in an unselected cohort of subjects participating in a screening program for diabetes. METHODS: A case-control study nested within a cohort of nondiabetic subjects with a mean follow-up of 27.7 ± 11.3 months was performed, comparing 40 cases of incident diabetes and 160 controls matched for age, sex, body mass index, fasting plasma glucose, 2-h post-load glycemia, smoking and alcohol abuse. RESULTS: When considering antihypertensive treatment at enrolment, a lower proportion of cases was exposed to ACE-inhibitors/angiotensin receptor blockers (ACE-i/ARB) in comparison with controls. A non-significant trend toward a higher exposure to diuretics, which were mainly represented by thiazide diuretics, was observed in cases. In a multivariate analysis, including both ACE-i/ARB and diuretics, a protective effect of ACEi/ARB, and an increased risk with diuretics were observed. Similar results were obtained in alternative models, after adjusting for systolic and diastolic blood pressure at enrolment, diagnosis of hypertension, concurrent treatment with ß-blockers or calcium-channel blockers, and number of antihypertensive medications. CONCLUSIONS: Diuretics seem to be associated with a higher incidence of diabetes, whereas treatment with ACEi/ARB could have a protective effect.

Hypertriglyceridaemic waist phenotype and ß-cell function in subjects with normal and impaired glucose tolerance.

AIM: To determine the association between the hypertriglyceridaemic waist phenotype, a combination of enlarged waist circumference and increased triglyceride levels, and ß-cell function in subjects with normal glucose tolerance and those with impaired glucose tolerance. METHODS: We studied 1344 outpatients clinic without diabetes. Overnight fasting blood samples were obtained to measure plasma glucose, insulin and lipids. An oral glucose tolerance test was performed in all subjects. All patients were divided in four groups, two groups with normal glucose tolerance and two with impaired glucose tolerance, with or without the hypertriglyceridaemic waist phenotype. Insulin resistance and ß-cell function were calculated by homeostatsis model assessment 2 indices. RESULTS: Twenty per cent of subjects showed the hypertriglyceridaemic waist phenotype and 23.8% had impaired glucose tolerance. We found a progressive significant increase (P < 0.001) of insulin resistance from subjects with normal glucose tolerance without the hypertriglyceridaemic waist phenotype with respect to patients with impaired glucose tolerance with the hypertriglyceridaemic waist phenotype. In subjects with normal glucose tolerance, the hypertriglyceridaemic waist phenotype was associated with a mild, but not significant, increase of homeostatsis model assessment 2-ß levels; but, in patients with impaired glucose tolerance, the hypertriglyceridaemic waist phenotype was associated with significantly lower homeostatsis model assessment 2-ß levels [127.0 (103.0-162.7) vs. 123.0 (96.0-147.0); P < 0.05]. The hypertriglyceridaemic waist phenotype displayed a higher (odds ratio 95% CI) ß-cell dysfunction of 1.8 (1.3-2.6) and insulin resistance of 5.0 (2.7-8.5) compared with 1.3 (0.9-1.9) and 2.4 (1.8-3.2), respectively, of waist circumference alone. CONCLUSION: In this study, the hypertriglyceridaemic waist phenotype is associated with increased insulin resistance and an overstimulation of ß-cell function in subjects with normal glucose tolerance, while patients with impaired glucose tolerance with the hypertriglyceridaemic waist phenotype showed a reduction in ß-cell function. These data suggest the importance of the identification of patients with impaired glucose tolerance combined with the hypertriglyceridaemic waist phenotype for an early intervention in relation to the high risk of developing Type 2 diabetes.

Relationship between GLP-1 levels and dipeptidyl peptidase-4 activity in different glucose tolerance conditions.

AIM: The reduced levels of glucagon-like peptide 1 (GLP-1) after an oral glucose load in Type 2 diabetic patients could be dependent either on a reduced synthesis or an increased degradation; but GLP-1 and dipeptidyl peptidase IV (DPP-IV) levels during an oral glucose tolerance test (OGTT) have not been studied together. The aim of the present study was to investigate GLP-1 and DPP-IV levels during an OGTT in patients with different degrees of glucose tolerance. METHODS: Fifty six subjects (34 female, 22 male) matched for sex, age, body mass index (BMI) and waist circumference underwent a 75 g oral glucose tolerance test. Twenty-eight had normal glucose tolerance, 15 had impaired glucose tolerance and 13 had Type 2 diabetes mellitus. GLP-1 assay was performed with an ELISA kit, and DPP-IV assay using a colorimetric method. RESULTS: At 30 min GLP-1 levels were significantly lower in subjects with impaired glucose tolerance and type 2 diabetes mellitus compared to those with normal glucose tolerance. The area under the GLP-1 curve was significantly different among the three groups; there was a significant decrease between subjects with normal and impaired glucose tolerance(P = 0.004) and between those with normal glucose tolerance and type 2 diabetes mellitus. (P < 0.001), while the area under the curve for DPP-IV showed no significant difference between the groups. CONCLUSIONS: These results suggest that an increase of GLP-1 degradation does not play a role in the early stages of diabetes mellitus.

Glucagon-like peptide-1 response to meals and post-prandial hyperglycemia in Type 2 diabetic patients.

BACKGROUND: The impaired response of glucagonlike peptide-1 (GLP-1) to meals in diabetic patients can contribute to the pathogenesis of impaired insulin secretion and post-prandial hyperglycemia. This study is aimed at the assessment of the relationship between meal-induced GLP-1 and post-prandial hyperglycemia in Type 2 diabetic patients. METHODS: Twenty-one drug-naïve Type 2 diabetic patients were studied. Blood glucose and active GLP-1 levels were measured 0, 30, 60, 90, and 120 min after a standard test meal. A continuous glucose monitoring (CGM) system was applied for the following 3 days. Nutrient intake at each meal was calculated on the basis of patients' food records. For each patient, post-prandial 120-min glucose incremental area under the curve (iAUC) was included in linear regression model exploring its relationship with total energy and carbohydrate intake, and the angular coefficient for total energy (EAC) and carbohydrate (CAC) was calculated. RESULTS: GLP-1 levels peaked 30 min after the test meal. Logarithmically transformed 60-min GLP-1 iAUC showed a significant inverse correlation with glycated hemoglobin (HbA1c) (p<0.01). A significant inverse correlation of 60-min GLP-1 iAUC was also observed with EAC and CAC (both p<0.01), meaning that patients with a lower GLP-1 response to the test meal had a higher increment of post-prandial glucose for each additional unit of total energy or carbohydrate intake. CONCLUSIONS: In Type 2 diabetic patients, a lower GLP-1 response to meals is associated with a higher HbA1c, and with a greater degree of meal-induced hyperglycemia, both in a meal test and during CGM in "real-life" conditions.

Lipoperoxidation and antioxidant capacity in patients with poorly controlled type 2 diabetes.

Type 2 diabetes is a heterogeneous disease resulting from insulin resistance and/or from a beta-cell secretory defect. Hyperglycemia, which occurs during type 2 diabetes, causes disorders of oxidative-antioxidative balance in the cells, leading to increased free-radical formation. Reduced antioxidant capacity is supposed to be one of the causes of the occurrence of complications in type 2 diabetes. The aim of this study was to evaluate lipoperoxidation and plasma antioxidant status in patients with poorly controlled type 2 diabetes with or without complications. In this study, 15 patients with type 2 diabetes without complications and 11 patients with type 2 diabetes with complications were enrolled. The 'ferric-reducing ability of plasma' showed no differences between the two experimental groups. A small, nonsignificant, Superoxide dismutase (SOD) activity reduction was observed in patients with diabetes with complications when compared to those patients with diabetes without complications; on the contrary, we found increased lipoperoxidation in patients with diabetes with complications compared with those patients with diabetes without complications. We also observed a positive correlation between malondialdehyde levels and high density lipoprotein or vitamin E in all analyzed patients with type 2 diabetes. Data obtained from our study show that patients with poorly controlled type 2 diabetes with complications have higher lipoperoxidation than patients with complication-free diabetes, although a residual compensatory response to hyperglycemia-induced oxidative stress occurs.

Treatment with insulin secretagogues and cancer-related mortality in type 2 diabetic patients a retrospective cohort study.

BACKGROUND: Recent evidence suggests that some hypoglycemic treatments could affect the incidence of malignancies. This study was aimed at the assessment of cancer-related mortality in type 2 diabetic patients treated with different hypoglycemic drugs. METHODS: A retrospective observational cohort study was performed on a consecutive series of 3002 type 2 diabetic outpatients. Cancer-related death was identified through the City Registry Office. For patients visited for the first time after January 1 (st), 2000, information on incidence of cancer was also available. RESULTS: During a mean follow-up of 4.3+/-2.5 years, 87 cases of cancer-related death were recorded, with a yearly incidence rate of 0.70%. Patients receiving secretagogues showed a significantly higher mortality than the rest of the sample (unadjusted OR [95%CI] 1.76 [1.15-2.69], p=0.009), which was maintained after adjustment for confounders (HR 2.29 [1.21-4.02], p=0.003). Conversely, no significant association of cancer-related mortality was observed with insulin sensitizers or exogenous insulin. In comparison with patients receiving no hypoglycemic treatment, those on secretagogue or insulin monotherapy showed a higher cancer-related mortality (HR 2.25 [1.10-4.78], p=0.034 and HR 2.11 [1.01-4.50], p=0.048, respectively). The effect of treatments on incidence of malignancies was similar to that observed on cancer-related death. CONCLUSIONS: Insulin secretagogues and, to a lesser extent, exogenous insulin, appear to be associated with increased mortality for cancer, even after adjustment for multiple confounders. This issue deserves further investigation through epidemiological studies on larger samples of patients.

National Cholesterol Education Program and International Diabetes Federation definitions of metabolic syndrome in the prediction of diabetes. Results from the FIrenze-Bagno A Ripoli study.

BACKGROUND: The International Diabetes Federation (IDF) proposed to modify the diagnostic criteria for metabolic syndrome (MS) previously issued by the National Cholesterol Education Program (NCEP). Aim of the present investigation is to compare the predictive value for diabetes of NCEP and IDF definitions of MS in a large sample of predominantly Caucasian subjects. METHODS: A prospective observational study was performed on a cohort study (n = 3096) enrolled in a diabetes-screening programme, the FIrenze-Bagno A Ripoli study. All subjects with fasting glucose >126 mg/dl and/or post-load glucose > or =200 mg/dl (5.7%) were excluded from the present analysis. Follow-up of each subject was continued until diagnosis of diabetes, death or until 31 December 2005. Mean follow-up was 27.7 +/- 11.3 months. RESULTS: Among subjects enrolled, 13.7 and 25.2% were affected by MS using NCEP and IDF criteria respectively. During follow-up, 38 new cases of diabetes were diagnosed, with a yearly incidence rate of 0.5%. The relative risk for diabetes in subjects with MS was 10.10 [5.13; 20.00] and 7.87 [3.70; 16.7] using NCEP and IDF definitions respectively. After adjustment for age, sex, fasting glucose and waist circumference, NCEP-defined MS, but not IDF-, was significantly associated with incident diabetes (hazard ratio, 95% CI: 2.41 [1.01; 5.95] and 2.05 [0.80; 5.29] respectively). CONCLUSIONS: Although the reasons for the proposed changes in diagnostic criteria for MS are easily understandable, the newer IDF definition, while increasing estimates of prevalence of the syndrome, reduces the effectiveness of MS in identifying subjects at risk for diabetes. Further research is needed before the previous NCEP criteria are abandoned.

Metabolic syndrome and pulse pressure.

AIM: Pulse pressure (PP) has been reported to be increased in patients with abdominal adiposity and insulin resistance. Aim of the present study is to verify the association of high PP with metabolic syndrome (MS) and with its individual components. METHODS: The relationship between PP and MS was studied in a sample of 1724 subjects aged (mean +/- s.d.) 52.8 +/- 1.3 years, enrolled in a screening programme for diabetes FIrenze-Bango A Ripoli (FIBAR) study, and in a consecutive series of 1775 patients with type 2 diabetes aged 64.3 +/- 9.1 years; only subjects not treated with antihypertensive medication were included in the analysis. RESULTS: In the FIBAR sample, PP was significantly higher in subjects with MS. A significant correlation of PP was found in women with waist circumference, fasting glucose and triglyceride (r = 0.14, 0.15, and 0.09 respectively), and in men with fasting glucose only (r = 0.09); the correlation was no longer significant after adjustment for age and mean blood pressure. Similar results were obtained in the series of patients with type 2 diabetes. DISCUSSION: High PP is associated with MS and its components, but this association seems to disappear after adjustment for age and mean blood pressure. On the basis of the present data, high PP cannot be considered as one of the alterations associated with MS.

National Cholesterol Educational Program and International Diabetes Federation diagnostic criteria for metabolic syndrome in an Italian cohort: results from the FIBAR Study.

BACKGROUND: The adoption of the International Diabetes Federation (IDF) criteria for metabolic syndrome (MS), in comparison with the National Cholesterol Educational Program (NCEP) criteria, produces different changes in estimates of prevalence in diverse populations. Few data are available in Caucasian non-diabetic subjects. PATIENTS AND METHODS: The prevalence of NCEP- and IDF-defined MS was assessed in a sample of 2,945 individuals, aged 55.2+/-11.5 yr, enrolled in a screening program for diabetes. Association of different definitions of MS with glucose intolerance (120-min glucose 7.8 mmol/l after a 75 g-oral glucose load) and hyperuricemia (>0.38 mmol/l) was also assessed. RESULTS: The prevalence of MS was 16.6% and 29.7% with NCEP and IDF definitions, respectively. The prevalence of NCEP-defined MS was higher than IDF-MS through all age ranges; among those aged >60 yr, the prevalence of IDF-MS reached 52.8% (vs 33.1% for NCEP-MS). Both NCEP- and IDF-MS were associated with glucose intolerance and hyperuricemia. Individuals fulfilling IDF, but not NCEP criteria for MS, showed a prevalence of glucose intolerance (22.7%) significantly (p<0.05) lower than those fulfilling NCEP criteria only (31.6%) or both sets of criteria (31.8%). CONCLUSION: In Caucasian subjects without known diabetes, IDF criteria produce a relevant increase in estimates of prevalence of MS, particularly in older subjects, when compared with NCEP criteria. NCEP-MS seems to be more effective than IDF-MS in the identification of glucose intolerant subjects.

Clinical phenotype and beta-cell autoimmunity in Italian patients with adult-onset diabetes.

OBJECTIVE: To characterize the phenotype of a large population of Italian patients with adult onset (> or =40 years) diabetes who were attending outpatient clinics and who were screened for glutamic acid decarboxylase 65 autoantibodies (GADA), protein tyrosine phosphatase IA-2 (IA-2A) and IA-2beta/phogrin (IA-2betaA). DESIGN AND METHODS: This was a cross-sectional study comprising a total of 881 patients, aged < or = 70 years, diagnosed with type 2 diabetes after the age of 40 years, and consecutively recruited in five clinics located in different geographic areas of Italy (Milan, Florence, Rome, Naples and Catania). Their mean disease duration was 8.1 (6.9; s.d.) years. GADA, IA-2A and IA-2betaA were measured with radiobinding assays with in vitro translated S-methionine-labelled glutamic acid decarboxylase 65 (GAD65) or IA-2 or IA-2beta. Anthropometric and clinical data were collected and compared amongst patients with or without autoantibodies. RESULTS: Sixty-three (7.1%) patients had one or more autoantibodies, 58 (6.6%) had GADA, 22 (2.5%) had IA-2A, six (0.7%) had IA-2betaA and 19 (2.15%) had two or more autoantibodies. IA-2A or IA-2betaA, in the absence of GADA, were found in only five patients. Autoantibody-positive patients were more often female (63.5 vs 36.5%; P < 0.009), had higher glycated haemoglobin (Hb A1c) (P < 0.001), lower body mass index (BMI; P < 0.0005) and waist/hip ratio (WHR; P < 0.01); female gender being the main contributor to BMI and WHR. We did not observe any differences in age at diagnosis or duration of disease with respect to the presence or absence of islet autoantibodies. The proportion of patients on insulin therapy was higher in patients with two or more antibodies, compared with those with one antibody only, and no antibodies (P for trend < 0.001), and among patients with GADA, in those with higher antibody titre (73.9% in those with > 10 units vs 42.0% in those with < or = 10 units; P < 0.007). CONCLUSIONS: Patients with adult onset diabetes characterized by autoimmunity to beta-cells showed a clinical phenotype with anthropometric features that differed from those classically observed in patients with type 2 diabetes. The number and titre of autoantibodies, which reflect the severity of autoimmunity and beta-cell impairment, amplified this difference. The usefulness of autoantibody screening in adult-onset diabetes is further emphasized by these findings.

Hyperglycaemia increases dipeptidyl peptidase IV activity in diabetes mellitus.

AIMS/HYPOTHESES: Chronic hyperglycaemia increases dipeptidyl peptidase IV (DPP-IV) activity in endothelial cells in vitro. The present study was designed to assess the effect of high glucose on circulating DPP-IV activity in patients with type 1 and type 2 diabetes. METHODS: Plasma DPP-IV activity was measured in 29 patients with type 1 diabetes and 29 age-, sex- and BMI-matched control subjects. We also assessed DPP-IV activity in 31 type 2 diabetic patients with HbA1c > 8.5% and in plasma from matched groups of 31 newly diagnosed diabetic subjects with HbA1c < 7.5%, 31 subjects with IGT and 62 subjects with NGT. In a further sample of 66 type 2 diabetic patients, a longitudinal study was also performed to evaluate variations in DPP-IV activity and HbA1c over 3 months. RESULTS: DPP-IV activity in type 1 diabetic patients was not significantly different from that in control subjects; however, a significant correlation between DPP-IV and HbA1c was observed in diabetic subjects (r = 0.47; p < 0.01). Type 2 diabetic patients with HbA1c > 8.5% showed significantly (p < 0.05) higher DPP-IV activity (mean+/-SD 27.7+/-7.1 U/l) than newly diagnosed diabetic patients and subjects with IGT (22.1+/-6.0 and 18.8+/-8.8 U/l, respectively). Variations in DPP-IV activity over 3 months in type 2 diabetic patients showed a significant positive correlation with variations in HbA1c (r = 0.26; p < 0.05). CONCLUSIONS/INTERPRETATION: Chronic hyperglycaemia induces a significant increase in DPP-IV activity in type 1 and type 2 diabetes. This phenomenon could contribute to the reduction in circulating active glucagon-like peptide-1 and to the consequent postprandial hyperglycaemia in type 2 diabetic patients with poor metabolic control.

Effects of metformin on glucagon-like peptide-1 levels in obese patients with and without Type 2 diabetes.

Metformin has been shown to increase glucagon-like peptide-1 (GLP-1) levels after an oral glucose load in obese non-diabetic subjects. In order to verify if this effect of the drug was also present in obese Type 2 diabetic patients who have never been treated with hypoglycemic drugs, 22 Type 2 diabetic and 12 matched non-diabetic obese patients were studied. GLP-1 was measured before and after a 100 g glucose load at baseline, after a single oral dose of 850 mg of metformin, and after 4 weeks of treatment with metformin 850 mg three times daily. Post-load GLP-1 levels were significantly lower in diabetic patients. A single dose of metformin did not modify GLP-1 levels. After 4 weeks of treatment, fasting GLP-1 increased in diabetic patients (3.8 vs 4.9 pmol/l; p<0.05), while the incremental area under the curve of GLP-1 significantly increased in both diabetic [93.6 (45.6-163.2) vs 151.2 (36.0-300.5) pmol x min/l; p<0.05] and non-diabetic [187.2 (149.4-571.8) vs 324.0 (238.2-744.0) pmol x min/l; p<0.05] subjects. In conclusion, GLP-1 levels after an oral glucose load in obese type 2 diabetic patients were increased by 4 weeks of metformin treatment in a similar fashion as in obese subjects with normal glucose tolerance.

Comparison among different insulin sensitivity indices in obese patients.

AIMS: Recently, several indices have been proposed for the measurement of insulin sensitivity (IS). We set out to make a comparison between fasting insulin, and different IS indices in obese subjects. PATIENTS AND METHODS: Fasting and post load (75 g) glucose and insulin were measured in a consecutive series of 767 (626 F, 141 M) obese (body mass index > 30 kg/m(2)) out-patients, with no known history of diabetes (DM). Mean (+/- sd) age was 46.7 +/- 13.8 years in females and 45.6 +/- 14.3 years in males. Indices of IS based on fasting homeostasis assessment model (HOMA) and post-load (ISI) glucose and insulin and either parameter (1A, and 1B scores) were determined. RESULTS: DM was diagnosed in 21.4% of females, and 20.6% of males, and impaired glucose tolerance in 24% females and 21.3% males. Fasting and post-load glucose, triglyceride and HDL-cholesterol were correlated with all indices in both sexes (P < 0.05). The relative risk of different conditions in the upper quartile of ISI was similar to that observed in the upper quartile of HOMA. The HOMA index was similarly associated with low HDL-cholesterol and hypertriglyceridaemia as fasting insulin, while it showed a greater association with diabetes; ISI was similarly associated with all three conditions as the HOMA index. CONCLUSIONS: Indices of IS based on fasting glucose and insulin show a greater association with diabetes, but not with other abnormalities related to insulin resistance, when compared with fasting insulin levels. Indices based on post-load glucose and insulin do not offer any advantage over those based on fasting values.

Fasting plasma glucose and glycated haemoglobin in the screening of diabetes and impaired glucose tolerance.

The use of fasting plasma glucose (FPG) only has been proposed for the screening and diagnosis of diabetes, but its sensitivity has been reported to be unsatisfactory. The use of HbA1C, alone or combined with FPG, has been suggested for the screening of diabetes and impaired glucose tolerance (IGT). In a sample of 1215 adult subjects without previously known diabetes, we assessed the sensitivity and specificity of FPG and HbA1C in diagnosing diabetes and IGT, determined by oral glucose tolerance test (OGTT). All lean diabetic patients, and 85% of overweight and obese diabetic individuals, had FPG > or =7 mmol/l. FPG >6.1 mmol/l had a sensitivity of 98.8% and a specificity of 32.9%; HbA1C had a lower specificity and sensitivity for the screening of diabetes. A screening strategy for diabetes based on FPG, with OGTT in all overweight subjects with FPG >6.1 mmol/l, is suggested. Neither FPG nor HbA1C is effective in the screening of IGT; although combined FPG and HbA1C could be useful for case finding, screening for IGT with OGTT is advisable in all subjects at high risk.

Effect of metformin on glucagon-like peptide 1 (GLP-1) and leptin levels in obese nondiabetic subjects.

OBJECTIVE: To evaluate the effects of metformin on glucagon-like peptide 1 (GLP-1) and leptin levels. RESEARCH DESIGN AND METHODS: A total of 10 obese nondiabetic male patients were studied before and after a 14-day treatment with 2,550 mg/day metformin and were compared with 10 untreated obese control subjects. On days 0 and 15, leptin and GLP-1(7-36)amide/(7-37) levels were assessed before and after an oral glucose load during a euglycemic hyperinsulinemic clamp to avoid the interference of variations of insulinemia and glycemia on GLP-1 and leptin secretion. The effects of metformin on GLP-1(7-36)amide degradation in human plasma and in a buffer solution containing dipeptidyl peptidase IV (DPP-IV) were also studied. RESULTS: Leptin levels were not affected by the oral glucose load, and they were not modified after metformin treatment. Metformin induced a significant (P < 0.05) increase of GLP-1(7-36)amide/(7-37) at 30 and 60 min after the oral glucose load (63.8 +/- 29.0 vs. 50.3 +/- 15.6 pmol/l and 75.8 +/- 35.4 vs. 46.9 +/- 20.0 pmol/l, respectively), without affecting baseline GLP-1 levels. No variations of GLP-1 levels were observed in the control group. In pooled human plasma, metformin (0.1-0.5 microg/ml) significantly inhibited degradation of GLP-1(7-36)amide after a 30-min incubation at 37 degrees C; similar results were obtained in a buffer solution containing DPP-IV. CONCLUSIONS: Metformin significantly increases GLP-1 levels after an oral glucose load in obese nondiabetic subjects; this effect could be due to an inhibition of GLP-1 degradation.

Glucagon-like peptide (GLP)-1 and leptin concentrations in obese patients with Type 2 diabetes mellitus.

AIMS: To assess differences in circulating leptin and glucagon-like peptide (GLP)-1 concentrations before and after an oral glucose load, in euglycaemic and isoinsulinaemic conditions, between obese patients with and without Type 2 diabetes mellitus. METHODS: Ten male obese (body mass index (BMI) > 30 kg/m2) patients with Type 2 diabetes and 20 matched non-diabetic subjects were studied. Leptin, GLP-1(7-36)amide and GLP-1(7-37) concentrations were measured 0, 30, 60, and 90 min after a 50-g oral glucose load administered 90 min after the beginning of a euglycaemic hyperinsulinaemic clamp. RESULTS: GLP-1(7-36)amide concentrations before the glucose load were significantly lower in diabetic patients than in controls (median (quartiles): 50.5 (44.7-53.2) vs. 128.7(100-172.5) pg/ml; P < 0.01), while no difference was observed in baseline GLP-1(7-37). In non-diabetic subjects, GLP-1(7-36)amide and GLP-1(7-37) concentrations increased significantly after the oral glucose load, while no glucose-induced increase in GLP-1 concentration was observed in diabetic patients. GLP-1(7-36)amide at 30, 60, and 90 min, and GLP-1(7-37) at 30 min, of the glucose challenge, were significantly lower in diabetic patients. Leptin concentrations were not significantly different in diabetic patients when compared to non-diabetic subjects, and they did not change after the oral glucose load. DISCUSSION: Leptin concentrations are not significantly modified in obese Type 2 diabetic patients. GLP-1(7-36)amide baseline concentrations are reduced in Type 2 diabetes; moreover, diabetic subjects show an impaired response of GLP-1 to oral glucose in euglycaemic, isoinsulinaemic conditions. This impairment, which is not the result of differences in glycaemia or insulinaemia during assessment, could contribute to the pathogenesis of hyperglycaemia in Type 2 diabetes mellitus.