scholarly journals Treatment with the Dipeptidyl Peptidase-4 Inhibitor Vildagliptin Improves Fasting Islet-Cell Function in Subjects with Type 2 Diabetes

2009 ◽  
Vol 94 (1) ◽  
pp. 81-88 ◽  
Author(s):  
David A. D'Alessio ◽  
Amanda M. Denney ◽  
Linda M. Hermiller ◽  
Ronald L. Prigeon ◽  
Julie M. Martin ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Blood Glucose ◽  
Cell Function ◽  
Glycosylated Hemoglobin ◽  
Fasting Blood Glucose ◽  
Dipeptidyl Peptidase ◽  
Islet Function ◽  
C Peptide ◽  
Dipeptidyl Peptidase 4

Abstract Context: Dipeptidyl peptidase 4 (DPP-4) inhibitors are proposed to lower blood glucose in type 2 diabetes mellitus (T2DM) by prolonging the activity of the circulating incretins, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1). Consistent with this mechanism of action, DPP-4 inhibitors improve glucose tolerance after meals by increasing insulin and reducing glucagon levels in the plasma. However, DPP-4 inhibitors also reduce fasting blood glucose, an unexpected effect because circulating levels of active GIP and GLP-1 are low in the postabsorptive state. Objective: The objective of the study was to examine the effects of DPP-4 inhibition on fasting islet function. Design: We conducted a randomized, double-blind, placebo-controlled trial. Setting: The study was performed in General Clinical Research Centers at two University Hospitals. Subjects: Forty-one subjects with T2DM were treated with metformin or diet, having good glycemic control with glycosylated hemoglobin values of 6.2–7.5%. Intervention: Subjects were treated with vildagliptin (50 mg twice daily) or placebo for 3 months, followed by a 2-wk washout. Major Outcome Measure: We measured insulin secretion in response to iv glucose and arginine before and after treatment and after drug washout. Results: There were small and comparable reductions in glycosylated hemoglobin in both groups over 3 months. Vildagliptin increased fasting GLP-1 levels in subjects taking metformin, but not those managed with diet, and raised active GIP levels slightly. DPP-4 inhibitor treatment improved the acute insulin and C-peptide responses to glucose (50 and 100% respectively; P < 0.05) and increased the slope of the C-peptide response to glucose (33%; P = 0.023). Conclusion: Vildagliptin improves islet function in T2DM under fasting conditions. This suggests that DPP-4 inhibition has metabolic benefits in addition to enhancing meal-induced GLP-1 and GIP activity.

Management of Patients with Type 2 Diabetes by Pharmacists in Primary Care Clinics

1998 ◽  
Vol 32 (6) ◽  
pp. 636-641 ◽  
Author(s):  
Elizabeth A Coast-Senior ◽  
Beverly A Kroner ◽  
Catherine L Kelley ◽  
Lauren E Trilli
Keyword(s):  
Type 2 Diabetes ◽  
Primary Care ◽  
Blood Glucose ◽  
Glycemic Control ◽  
Glycosylated Hemoglobin ◽  
Fasting Blood Glucose ◽  
Face To Face ◽  
Primary Care Clinics ◽  
Blood Glucose Concentrations

OBJECTIVE: To determine the impact of clinical pharmacists involved in direct patient care on the glycemic control of patients with type 2 diabetes mellitus. DESIGN: Eligible patients included those with type 2 diabetes who received insulin or were initiated on insulin therapy by the pharmacists and were willing to perform self-monitoring of blood glucose. The pharmacists provided diabetes education, medication counseling, monitoring, and insulin initiation and/or adjustments. All initial patient interactions with the pharmacists were face-to-face. Thereafter, patient–pharmacist interactions were either face-to-face or telephone contacts. SETTING: Two primary care clinics in a university-affiliated Veterans Affairs Medical Center. PARTICIPANTS: Study subjects were patients with type 2 diabetes who were referred to the pharmacists by their primary care providers for better glycemic control. OUTCOME MEASURES: Primary outcome variables were changes from baseline in glycosylated hemoglobin, fasting blood glucose, and random blood glucose measurements. Secondary outcomes were the number and severity of symptomatic episodes of hypoglycemia, and the number of emergency room visits or hospitalizations related to diabetes. Twenty-three veterans aged 65 ± 9.4 years completed the study. Fifteen (65%) patients were initiated on insulin by the pharmacists; 8 (35%) were already using insulin. Patients were followed for a mean ± SD of 27 ± 10 weeks. Glycosylated hemoglobin, fasting blood glucose concentrations, and random blood glucose concentrations significantly decreased from baseline by 2.2% (p = 0.00004), 65 mg/dL (p < 0.01), and 82 mg/dL (p = 0.00001), respectively. Symptomatic hypoglycemic episodes occurred in 35% of patients. None of these episodes required physician intervention. CONCLUSIONS: This study demonstrates that pharmacists working as members of interdisciplinary primary care teams can positively impact glycemic control in patients with type 2 diabetes requiring insulin.

Vildagliptin An Oral Dipeptidyl Peptidase-4 Inhibitor for Type 2 Diabetes

2006 ◽  
Vol 00 (02) ◽  
Author(s):  
Eberhard Standl ◽  
Martin Fuchtenbusch ◽  
Michael Hummel
Keyword(s):  
Type 2 Diabetes ◽  
Large Scale ◽  
Cell Function ◽  
Glucagon Secretion ◽  
Postprandial Glucose ◽  
Dipeptidyl Peptidase ◽  
Β Cell ◽  
Dipeptidyl Peptidase 4 ◽  
Β Cell Function

Vildagliptin is a member of a new class of oral antidiabetogenic agents known as dipeptidyl peptidase-4 (DDP-4) inhibitors.These drugs enhance islet function by improving α- and β-cell responsiveness to glucose. Mechanism of action studies in patients with type 2 diabetes show that vildagliptin increases plasma levels of active glucagon-like peptide-1, improves glucosedependent insulin secretion and β-cell function, improves insulin sensitivity, reduces inappropriate glucagon secretion, reduces fasting and postprandial glucose, and decreases HbA1c. Large-scale treatment trials with vildagliptin 50mg or 100mg per day as monotherapy or in combination in drug-naïve patients or as add-on therapy to on-going anti-diabetic treatment show that it is effective in reducing HbA1c (with greater decreases occurring in patients with higher initial HbA1c levels), maintains efficacy in glycemic control as monotherapy for at least 1 year, is associated with infrequent hypoglycemia, and does not cause weight gain.

Glycemic Monitoring in Diabetics with Sickle Cell Plus β-Thalassemia Hemoglobinopathy

2005 ◽  
Vol 39 (9) ◽  
pp. 1557-1560 ◽  
Author(s):  
Sheri M Kosecki ◽  
Philip T Rodgers ◽  
Martha B Adams
Keyword(s):  
Type 2 Diabetes ◽  
Blood Glucose ◽  
Sickle Cell Disease ◽  
Glycemic Control ◽  
Sickle Cell ◽  
Diabetes Management ◽  
Glycosylated Hemoglobin ◽  
Fasting Blood Glucose ◽  
Cell Disease

OBJECTIVE: To report a case of diabetes management in a patient with a hemoglobinopathy that caused her clinician to seek a different measure of glycemic control, fructosamine, rather than glycosylated hemoglobin (HbA1c). CASE SUMMARY: A 53-year-old African American woman presented with a past medical history of type 2 diabetes, hypertension, seizure disorder, rheumatoid arthritis, and sickle cell disease plus β-thalassemia. She reported fasting blood glucose values ranging broadly from 50 to 320 mg/dL, yet her HbA1c result remained steady in a low range of >6%. A measure of fructosamine returned elevated at 340 μmol/L (reference range 200–300%). DISCUSSION: We believe that this patient's hemoglobinopathy resulted in falsely low levels of HbA1c, and we substantiate this interpretation with the patient's self-monitored blood glucose values from home that appeared higher and inconsistent with the HbA1c results. Although few reports on using the measure of fructosamine appear in the literature, this patient's high fructosamine result supports fructosamine as the more appropriate measure of glycemic control. CONCLUSIONS: Serum fructosamine levels may be considered as an appropriate laboratory measurement when monitoring long-term glycemic control in patients with type 2 diabetes mellitus and sickle cell disease.

Islet Cell Function Its Role in the Onset and Progression of Type 2 Diabetes

2006 ◽  
Vol 00 (02) ◽  
Author(s):  
Roy Taylor
Keyword(s):  
Type 2 Diabetes ◽  
Blood Glucose ◽  
Natural History ◽  
Cell Function ◽  
Fasting Blood Glucose ◽  
Blood Glucose Control ◽  
Normal Function ◽  
Dietary Advice ◽  
Islet Cell Function

Studies of the natural history of type 2 diabetes have transformed views on the nature of the condition in the last two decades.The Belfast Study is one of the earliest and most complete studies to observe the change in blood glucose control during six years of best possible management by dietary means. After the rapid initial fall from presenting blood glucose levels over 11mM, mean fasting blood glucose was maintained around 8mM for only two years before an inexorable rise occurred. By six years after diagnosis mean plasma glucose was over 10mM.This work is all the more impressive as no oral agent therapy was used during the course of the study which truly observed natural history modified only by consistent and expert dietary advice. Calculated beta cell function revealed a fall from around 30% of normal function at diagnosis to around 22% after six years.

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