Sulfonylureas and their use in clinical practice.

Many anti-diabetic drugs with different mechanisms of action are now available for treatment of type 2 diabetes mellitus. Sulfonylureas have been extensively used for treatment of type 2 diabetes for nearly 50 years and, even in our times, are widely used for treatment of this devastating chronic illness. Here, we review some of the available data on sulfonylureas, evaluating their mechanism of action and their effects on glycemic control. We can conclude that sulfonylureas are still the most used anti-diabetic agents: maybe this is due to their lower cost, to the possibility of mono-dosing and to the presence of an association with metformin in the same tablet. However, sulfonylureas, especially the older ones, are linked to a greater prevalence of hypoglycemia, and cardiovascular risk; newer prolonged-release preparations of sulfonylureas are undoubtedly safer, mainly due to reducing hypoglycemia, and for this reason should be preferred.

Oral glucose tolerance test-based calculation identifies different glucose intolerance phenotypes within the impaired fasting glucose range.

AIMS/INTRODUCTION: The conventional oral glucose tolerance test (OGTT) cannot detect future diabetics among isolated impaired fasting glucose (is-IFG) nor normal glucose tolerant (NGT) groups. By analyzing the relationship between fasting (FPG) and 2-h plasma glucose (2hPG), the present study identifies is-IFG subjects liable to worsening glucose homeostasis. MATERIALS AND METHODS: Oral glucose tolerance test was carried out in 619 patients suffering from obesity, hypertension or dyslipidemia, whose FPG was in the 100-125 mg/dL range. We calculated the percentage increment of 2hPG with respect to FPG (PG%) in these patients using the formula: ([2hPG - FPG] / FPG) × 100. Differences in ß-cell function within is-IFG patients were assessed by estimated insulin sensitivity index (EISI), first-phase insulin release (1stPH) and 1stPH/1/EISI (1stPHcorrected). RESULTS: Diabetes was diagnosed in 69 patients (11.2%), combined IFG/impaired glucose tolerance (IGT) in 185 patients (29.9%) and is-IFG in 365 patients (58.9%). Is-IFG was subdivided into PG% tertile groups: the percentage of females increased from 25% in the lowest to 45.2% in the highest tertile (χ(2) = 18.7, P < 0.001). Moving from the lowest to the highest PG% tertile group, insulin and 2hPG concentrations rose, whereas FPG, EISI, and 1stPHcorrected decreased progressively and significantly. Furthemore, PG% correlated inversely with EISI (r = -0.44, P < 0.0001) and 1stPHcorrected (r = -0.38, P < 0.0001). CONCLUSIONS: Oral glucose tolerance test does differentiate the great heterogeneity in metabolic disorders of patients with FPG 100-125 mg/dL. Furthermore, PG% can expand the diagnostic power of OGTT in the is-IFG range by distinguishing metabolic phenotypes very likely to herald different clinical risks.

Impaired glucose metabolism in hypertensive patients with/without the metabolic syndrome.

BACKGROUND: In hypertension clinics, screening patients for the metabolic syndrome (MetS) is common practice, while performing the cumbersome oral glucose tolerance test (OGTT) is not. How large is the underestimation of diabetes and prediabetes that ensues is unknown. METHODS: We recruited N=1397 patients with essential arterial hypertension who underwent a 75-g OGTT and were classified as normally glucotolerant (NGT) or having impaired glucose metabolism (IGM), and as affected or not by MetS (ATPIII criteria). The agreement between the OGTT and the ATPIII criteria in attributing a high cardiovascular risk was estimated by matching the categories of MetS and no-MetS with NGT and IGM. RESULTS: n=677/1397 patients (48%) satisfied criteria for MetS, while n=757/1397 (54%) had an IGM. MetS and IGM were both present in n=512/1397 patients (36.6%), and both absent in n=475/1397 (34%). Further n=410/1397 patients (29%) were discordant for the two conditions: n=165/410 (40%) had the MetS but were NGT, and n=245/410 (60%) had IGM but no MetS. Among IGM patients, n=168/757 (22%; of which 45 had no MetS) received a new diagnosis of diabetes based on OGTT criteria. Among all discordant patients, those with IGM and no MetS were more commonly males (p<0.001), and had older age (p<0.001) and lower body mass index (p<0.05). CONCLUSIONS: Among patients with hypertension, the estimate of the prevalence of diabetes and prediabetes, hence of the global cardiovascular risk, can be seriously flawed unless an OGTT is performed. Our results support a wider use of the OGTT in the management of hypertension.

Sex differences in lipid profiles in relation to the progression of glucose abnormalities.

BACKGROUND: In the present study, we investigated the role of changes in blood lipids in the abolition of the lower cardiovascular risk associated with the female gender in individuals with type 2 diabetes mellitus (T2DM). METHODS: An oral glucose tolerance test (OGTT) was performed in 1091 consecutive patients (478 men and 613 women) and patients were divided into groups as follows: (i) those with normal glucose tolerance (NGT; n = 589); (ii) those with pre-diabetes (pre-T2DM), who were further divided into those with impaired fasting glucose (IFG; n = 212), impaired glucose tolerance (IGT; n = 84), and both IFG and IGT (IFG/IGT; n = 102); and (iii) those with T2DM (n = 104). Total cholesterol, triglycerides, high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), apolipoprotein (apo) A-I, apoB, and the apoB:apoA-I ratio were determined in each patient. Differences in lipids between the different groups were assessed using Student's t-test. RESULTS: Significantly higher triglyceride levels and an apoB:apoA-I ratio were found in NGT men (P < 0.0001), along with lower HDL-C and apoA-I (P < 0.0001). Men in the pre-T2DM group maintained a higher apoB:apoA-I ratio (P < 0.05) and lower HDL-C (P < 0.0001) compared with women. In the T2DM group, only HDL-C was lower in men compared with women (P < 0.05). CONCLUSIONS: The progression of glucose intolerance from NGT to pre-T2DM and T2DM exhibits striking sex differences regarding the lipid profile. The data demonstrate a worsening of plasma lipid composition in women who become diabetic. This could explain, at least in part, the loss of the more favorable cardiovascular risk normally associated with NGT women.