E. Bartoli

The oral glucose tolerance test (OGTT) revisited

The oral glucose tolerance test (OGTT) has been the mainstay for diagnosing diabetes for decades. Recently, the American Diabetes Association (ADA) suggested abandoning the OGTT, while resorting to a simpler screening test, exclusively based on baseline fasting blood glucose concentration. This review article rewinds the history of OGTT and its recent advancements, and compares its power in detecting early diabetes with that of fasting blood glucose alone. The key point is that there are more diabetics originating from a population with normal fasting blood glucose than from subjects with impaired fasting glucose, those who can be detected by the new ADA recommendations. Conversely, the OGTT detects more efficiently early diabetes as well as subjects with IGT, as the glycemia at the second hour seems crucial as a diagnostic tool. We discuss the different significance of fasting versus second hour glycemia during OGTT, according to different mechanisms of glucose homeostasis. Finally, we provide recent evidence on very simple additional information that can be obtained from the OGTT, which renders this test even more useful, discussing pathophysiologic significance.

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.

Methods for the quantitative assessment of electrolyte disturbances in hyperglycaemia.

AIMnWhile empirical calculations are presently used, exact solutions to compute volume and solute changes of hyperosmolar coma (HC) can be obtained by subdividing the patients according to well defined clinical and laboratory conditions. These are represented by PNa(G), the plasma Na concentration that would be present if there were only glucose addition (GA), that discloses prevalent Na depletion when >PNa(1), prevalent water deficit when <PNa(1) (value measured during HC). Exact solutions are available when Na is lost as NaCl, and when patients are subdivided according to Posm(1) (plasma osmolality during HC) >, = or <Posm(0) (the normal value). When Posm(1)=Posm(0), GA must equal the loss of ions induced by the osmotic diuresis (2 x DeltaNa), and the math solution is exact. We herein report data validating these new computational methods.nnnDATA SYNTHESISnWe built a mathematical model describing fluid derangements used to execute computer-simulated experiments of HC. The derangements were generated on the computer by adding, to the extra-cellular volume, different amounts of glucose while subtracting variable combinations of ions and solvent. The model yielded true solute concentrations from which our formulas computed the amounts lost or gained. These were identical to the true changes introduced to simulate the derangements (R(2)=1.00, P<0.0001) when the boundary conditions for PNa(G), exclusive NaCl loss and Posm(1)-Posm(0) were met. In patients with HC in whom these same boundary conditions were satisfied, the computations of glucose and Na changes with our new formulas were not significantly different from those estimated after correction of the derangements, considered true values (R(2)=0.60, P<0.05), and showed a satisfactory agreement with the clinical evaluation.nnnCONCLUSIONSnOur new methods are more accurate than the traditional ones, as they reach a better quantitative assessment of the entity of the derangements, avoiding iatrogenic dysnatraemias after correction of HC.

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

Background:u2002 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).

The significance of the furosemide test for predicting ascites control by diuretics in cirrhotics: A comparison with volume expansion and octreotide infusion

To verify prospectively the usefulness of the furosemide-induced natriuresis test in predicting ascites control by medical treatment, 15 stable cirrhotics (9 male) with ascites were studied. Sodium excretion was measured after this test and after volume expansion with saline associated with intravenous infusion of octreotide; 6 months later, response to medical treatment was rated as good (N=9) or poor (N=6). Patients with poor ascites control had lower sodium excretion with the furosemide-induced natriuresis test (median, 88 vs 201xa0mmol; P < 0.01). Poor control was observed in four of four patients with sodium excretion ≤125xa0mmol, and good control in six of six patients with sodium excretion >175xa0mmol (P < 0.002). Volume expansion was followed by limited natriuresis (median, 20xa0mmol), in inverse relationship with plasma active renin concentration (P < 0.001). In conclusion, long-term ascites control is well predicted by the furosemide-induced natriuresis test.

Individuation of different metabolic phenotypes in normal glucose tolerance test.

Based on the hypothesis that a more efficient glucose utilization lowers the risk of progression to type 2 diabetes, we tested the capability of oral glucose tolerance test (OGTT) to identify subjects at risk included inside normal glucose tolerance (NGT). We measured fasting and 2-h plasma glucose (FPG and 2hPG) and insulin values (FPI and 2hPI) in 623 normal OGTTs. Insulin sensitivity and secretion were computed with HOMA2 method and Stumvoll’s formula. Secretion was expressed as HOMA2%β, first (1stPH) and second-phase (2ndPH) insulin release. The percentage increment of 2hPG with respect to FPG (PG%) was used to subdivide patients into PG% tertiles, considered as the primary grouping variable. Covariance analysis (ANCOVA) for multiple comparisons was performed considering the above measurements as dependent variables, sex, age, body mass index (BMI) and waist circumference as covariates. In subjects with PG% ≤0, we documented significant increments of insulin sensitivity and significant decrements of resistance and secretion compared to subjects with PG% >0. ANCOVA disclosed that insulin sensitivity fell, while 1stPH secretion rose significantly from the lower to the higher tertile of PG%. OGTT may be useful to establish NGT as well as a more subtle metabolic phenotype. The closer 2hPG is to FPG, the higher insulin sensitivity and the lower insulin secretion are. The stimulus to maintain NGT elicits more insulin secretion, predisposing to worsening glucose tolerance when a faltering insulin secretion ensues. These subjects could benefit from prospective prevention treatment and studies.

Expanding the clinical use of standard OGTT: the percentage increment of 2 h with respect to fasting glucose as an index of β-cell dysfunction.

Since glucose levels during oral glucose tolerance test (OGTT) are determined both by insulin sensitivity and insulin secretion, we investigated whether the percentage increment (PG%) of 2‐h plasma glucose (2hPG) over fasting plasma glucose (FPG) is related to validated indexes of insulin sensitivity and insulin secretion.

Leishmaniasis Mimicking Lymphoma and/or Liver Cirrhosis

A 76-year-old man was admitted to hospital with fever, weight loss, pancytopenia, hepatosplenomegaly and a double monoclonal component IgM-IgG-k, suggesting a diagnosis of myeloma. Bone marrow and liver biopsies disclosed the presence of Donovan bodies, and the titre of anti-Leishmania antibodies was extremely high. After treatment with liposomal amphotericin B, the titre of antibodies fell considerably, while monoclonal components, pancytopenia and clinical symptoms slowly disappeared. Polyclonal γ-globulins are made of innumerable monoclonal components, one of which can appear as a recognizable band and be misdiagnosed as myeloma when representing the high titre of an antibody directed towards a specific antigen.

The Management of Type 2 Diabetic Patients with Hypoglycemic Agents

Aims and Scope. Aims of the paper are to suggest the best treatment to improve the glycemic control in patients with Type 2 diabetes using hypoglycemic agents, in particularly, we think that every patient is different from another one in terms of BMI, family history, duration of the disease and so on. We propose for every clinical aspect the best hypoglycemic agents to use, considering the scientific evidence and physiopathology.

P03-129 - Atypical neuroleptics and glucose metabolism: A study project

Introduction Metabolic syndrome and cardiovascular diseases are important causes of morbidity and mortality among patients with mental illness. Atypical antipsychotics are more associated with obesity, metabolic syndrome, abnormal glucose and lipid metabolism than first generation antipsychotics. Objectives To identify risk factors related to glucose metabolism in short, medium and long time treatment and find out which are related to neuroleptic therapy and which depends on genetic background and lifestyle. To follow up clinical and self-rated variations of the psychiatric symptoms. Methods We included psychotic or bipolar patients in treatment with only one typical (haloperidol) or atypical (clozapine, olanzapine, risperidon, aripiprazole, paliperidon) neuroleptic, drug-naive or after a wash-out from previous therapy. Patients will be evaluated five times (at baseline and after 1, 3, 6, 12 months) with a blood sample (haemocrome, glucose, insulin, Hb A1C, thyroid hormones, liver and pancreatic function), BMI, Basal Metabolic Rate (BMR), OGTT, HOMA index, familiar and pharmacological history, SIDE and CGI. Results From blood exams and OGTT we will obtain data regarding variations of glucose metabolism and the possible relationship with neuroleptic medications. From SIDE questionnaire we will assess the impact of side-effects by the patients perspective and with CGI the variations of symptom severity. Conclusions Our study will allow us to identify risk factors concerning glucose metabolism alterations related to antipsychotic medications.