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Biomedical subjects

F Ovalle

Publications and source records attributed to F Ovalle.

At least 19 recordsLinked to original sources
PubMed2006

Long-term glycaemic efficacy and weight changes associated with thiazolidinediones when added at an advanced stage of type 2 diabetes.

OBJECTIVE: To describe the outcome of 35 patients with type 2 diabetes prospectively followed for 6 years after the addition of a thiazolidinedione (TZD) to a failing regimen of a sulphonylurea and metformin -- triple oral therapy. METHODS: Study patients were assessed for the need for the addition of insulin to their regimen, and follow-up clinical and laboratory findings were analysed. RESULTS: At a mean follow-up of 72 +/- 1.5 months (range 53-80), 18 (51%) of patients remained well controlled on triple oral therapy with a mean glycosylated haemoglobin (HbA1c) value of 6.9 +/- 0.2% (upper limit of normal 6.2%). In 17 other patients, triple oral therapy failed and the use of insulin was necessary after a mean duration of 38 (range 18-68) months. The mean HbA1c in these patients was 8.0 +/- 0.3%. The group that was maintained on triple oral therapy gained 15.2 +/- 1.9 lbs over the 6-year study which was significantly higher than the baseline weight. Alternatively, the group that failed and had insulin added to their therapy gained 20.2 +/- 4.5 lbs over the same period which was also significantly different from baseline but not from the triple oral therapy group. Although after 3 years a trend towards weight loss occurred in the triple oral therapy group, the insulin-added group continued to gain weight. Stimulated C-peptide levels increased significantly in the triple therapy group from 3.6 +/- 0.9 to 4.3 +/- 1.2 ng/ml and had not increased or decreased non-significantly from 3.7 +/- 0.8 to 3.2 +/- 0.6 ng/ml at the time of insulin initiation in the insulin-requiring group. CONCLUSION: When used late in the course of type 2 diabetes, TZDs result in improved and prolonged glycaemic control which persisted for a median time of 6 years. Weight gain with TZDs peaks and then plateaus (and even trends downwards) at 3 years, although the addition of insulin to a failing oral therapy regimen results in a further and continuing weight gain in spite of inferior glycaemic control. Continuing glycaemic control with triple oral therapy is dependent on preservation or augmentation of endogenous insulin production.

Administration, Oral↗
PubMed2004

Outcomes of initiation of therapy with once-daily combination of a thiazolidinedione and a biguanide at an early stage of type 2 diabetes.

CONTEXT: Utilization of the biguanide metformin and a thiazolidinedione (TZD) with new onset diabetes has the benefit of lowering A1cs into the normal range without the problem of severe hypoglycaemia. OBJECTIVE: To assess the effectiveness of once-daily combined metformin and TZD therapy compared with other therapeutic regimens typically utilized at later stages of type 2 diabetes. METHODS: A random chart review of 300 type 2 diabetic patients and extraction of data for body mass index (BMI), duration of diabetes and C-peptide and A1c was performed. In the 210 type 2 diabetic subjects in whom this information was currently available, the data were analysed. RESULTS: Eighty-six patients on once-daily metformin and rosiglitazone had an average A1c of 6.2% (group A), and 58 subjects on triple therapy (metformin, rosiglitazone and glimepiride) (group B) had an average haemoglobin A1c (HbA1c) of 6.9%. The 22 subjects on one injection of insulin per day in addition to triple therapy (group C) had an average HbA1c of 7.6%, and the 44 subjects on more than one insulin injection per day plus metformin and/or rosiglitazone (group D) had an average HbA1c of 8.3%. HbA1cs below 7.0% were found in 91.9% of group A, 21.7% of group B, 36.4% of group C and 56.8% of group D. HbA1cs below 6.5% were found in 78.2% in group A, 15.5% in group B, 22.7% in group C and 31.8% in group D. HbA1cs below 6.0% were found in 41.9% in group A, 6.9% in group B, 9.1% in group C and 13.6% in group D. On univariate analyses, the HbA1c was positively associated with the duration of diabetes and the BMI and negatively associated with random C-peptide levels. Alternatively, on multiple regression analysis, there was no statistical correlation between the duration of diabetes or BMI with the HbA1c. However, there was a strong statistical correlation between the random C-peptide level and the HbA1c (p = 0.002). CONCLUSION: Early initiation of therapy for type 2 diabetes with a once-daily combination of metformin and rosiglitazone provides the greatest opportunity to achieve A1cs within the normal range. The level of achieved glycaemic control is not dependent on the number or potency of the therapies utilized but is dependent on the level of endogenous insulin production. The use of a TZD as part of initial therapy of type 2 diabetes with its documented ability to preserve or improve beta-cell function has the potential to achieve prolonged normoglycaemia in the type 2 diabetic patient.

Body Mass Index↗
PubMed2002

Clinical evidence of thiazolidinedione-induced improvement of pancreatic beta-cell function in patients with type 2 diabetes mellitus.

BACKGROUND: There is growing evidence in animal and in vitro studies showing that thiazolidinediones (TZDs) improve pancreatic beta cell (beta-cell) function. The aim of this study was to evaluate the effect of thiazolidinediones on the beta-cell function of patients with Type 2 diabetes mellitus (T2DM) in clinical practice. PATIENTS AND METHODS: This is an observational, nested case-control study. We identified 28 patients (TZD group), with T2DM, who had had a meal-stimulated C-peptide level documented before the addition of troglitazone to a failing double-therapy regimen with metformin (MET) and sulphonylurea (SU). As a control group (CTRL), we identified 26 patients, with T2DM, who also had had a meal-stimulated C-peptide documented before adding MET to a failing SU monotherapy regimen. We then proceeded to prospectively remeasure their meal-stimulated C-peptide levels and compared the changes over time between the two groups. RESULTS: Both groups were well matched for age, body mass index (BMI), and HgbA1c before and after treatment. The C-peptide in the TZD group increased significantly during therapy (from 3.2 +/- 0.5 to 4.2 +/- 0.5, p = 0.01), whereas it remained unchanged in the CTRL group (from 4.8 +/- 0.6 to 5.0 +/- 0.5, p = 0.74). The C-peptide/glucose ratio also increased significantly in the TZD group (from 1.9 +/- 0.3 to 3.1 +/- 0.3, p = 0.0003) whereas it remained unchanged in the CTRL group (from 3.4 +/- 0.7 to 3.4 +/- 0.3, p = 0.97). Furthermore, the C-peptide/glucose ratio of the TZD group, which was significantly lower at baseline compared with the CTRL group (1.9 +/- 0.3 vs. 3.4 +/- 0.7, p = 0.04), caught up to its level during treatment (3.1 +/- 0.3 vs. 3.4 +/- 0.3, p = 0.48). CONCLUSION: Thiazolidinediones seem to induce recovery of pancreatic beta cell function, independently of the correction of glucose toxicity.

Biomarkers↗
PubMed1998

Impact of nocturnal hypoglycemia on hypoglycemic cognitive dysfunction in type 1 diabetes.

To test the hypothesis that glycemic thresholds for cognitive dysfunction during hypoglycemia, like those for autonomic and symptomatic responses, shift to lower plasma glucose concentrations after recent antecedent hypoglycemia in patients with type 1 diabetes mellitus (T1DM), 15 patients were studied on two occasions. Cognitive functions were assessed during morning hyperinsulinemic stepped hypoglycemic clamps (85, 75, 65, 55, and 45 mg/dl steps) after, in random sequence, nocturnal (2330-0300) hypoglycemia (48 +/- 2 mg/dl) on one occasion and nocturnal euglycemia (109 +/- 1 mg/dl) on the other. Compared with nondiabetic control subjects (n = 12), patients with T1DM had absent glucagon (P = 0.0009) and reduced epinephrine (P = 0.0010), norepinephrine (P = 0.0001), and neurogenic symptom (P = 0.0480) responses to hypoglycemia; the epinephrine (P = 0.0460) and neurogenic symptom (P = 0.0480) responses were reduced further after nocturnal hypoglycemia. After nocturnal hypoglycemia, in contrast to nocturnal euglycemia, there was less deterioration of cognitive function overall (P = 0.0065) during hypoglycemia based on analysis of the sum of standardized scores (z-scores). There was relative preservation of measures of pattern recognition and memory (the delayed non-match to sample task, P = 0.0371) and of attention (the Stroop arrow-word task, P = 0.0395), but not of measures of information processing (the paced serial addition task) or declarative memory (the delayed paragraph recall task), after nocturnal hypoglycemia. Thus, glycemic thresholds for hypoglycemic cognitive dysfunction, like those for autonomic and symptomatic responses to hypoglycemia, shift to lower plasma glucose concentrations after recent antecedent hypoglycemia in patients with T1DM.

Adult↗
PubMed1998

Brief twice-weekly episodes of hypoglycemia reduce detection of clinical hypoglycemia in type 1 diabetes mellitus.

We tested the hypothesis that as few as two weekly brief episodes of superimposed hypoglycemia (i.e., doubling the average frequency of symptomatic hypoglycemia) would reduce physiological and behavioral defenses against developing hypoglycemia and reduce detection of clinical hypoglycemia in patients with type 1 diabetes mellitus (T1DM). Compared with nondiabetic controls, six patients with well-controlled T1DM (HbA1c, 7.5 +/- 0.7% [mean +/- SD]) exhibited absent glucagon responses and reduced epinephrine (P = 0.0027), norepinephrine (P = 0.0007), pancreatic polypeptide (P = 0.0030), and neurogenic symptom (P = 0.0451) responses to hypoglycemia as expected. In these patients, 2 h of induced hypoglycemia (50 mg/dl, 2.8 mmol/l) twice weekly for 1 month, compared in a random-sequence crossover design with an otherwise identical 2 h of induced hyperglycemia (150 mg/dl, 8.3 mmol/l) twice weekly for 1 month, further reduced the epinephrine (P = 0.0001) and pancreatic polypeptide (P = 0.0030) responses, tended to further reduce the norepinephrine and neurogenic symptom responses to hypoglycemia, and reduced cognitive dysfunction during hypoglycemia (P = 0.0271), all assessed in the investigational setting. In the clinical setting, induced hypoglycemia did not alter overall glycemic control, but did reduce the total number of symptomatic hypoglycemic episodes detected by the patients from 49 to 30 per month and lowered the mean +/- SE self-monitored blood glucose level during symptomatic hypoglycemia from 51 +/- 2 mg/dl (2.8 +/- 0.1 mmol/l) to 46 +/- 3 mg/dl (2.6 +/- 0.2 mmol/l) (P < 0.01). It also reduced the proportion of low regularly scheduled self-monitored values that were symptomatic by approximately 33%. Thus as little as doubling the frequency of symptomatic hypoglycemia further reduced both the key epinephrine response and clinical awareness of developing hypoglycemia, changes reasonably expected to increase the risk of severe iatrogenic hypoglycemia in T1DM.

Adult↗
PubMedDate not supplied

Triple oral antidiabetic therapy in type 2 diabetes mellitus.

To determine the effectiveness of triple oral antidiabetic therapy with a sulfonylurea, a biguanide, and a thiazolidinedione, we analyzed the results in 35 patients who had previously had inadequate glycemic control with a combination of glimepiride and metformin. The study cohort consisted of 27 men and 8 women (mean age, 55.8 years) who had had type 2 diabetes mellitus for a mean duration of 8.7 years. The addition of troglitazone (600 mg/day administered with the largest meal) to the glimepiride and metformin therapy yielded normal or near-normal glycemia in all 35 patients. Glycemic control was initially associated with mean weight gain; subsequently, however, mean weight was reduced to below the baseline level--perhaps attributable to the anorectic effect of metformin. Thus, for the first time, triple oral antidiabetic therapy with glimepiride, metformin, and troglitazone has been shown to be an efficacious therapeutic option for type 2 diabetes.

Journal Article↗
PubMedDate not supplied

C-Peptide utilization in clinical practice: effect on treatment and outcome of diabetes in a series of cases.

OBJECTIVE: To emphasize that measurement of a C-peptide level can be critical in the diagnosis and appropriate management of patients with diabetes mellitus. METHODS: We present a series of clinical cases in which glycemic control proved challenging, and we discuss the underlying pathophysiologic features of type 1 versus type 2 diabetes. RESULTS: In a series of 12 illustrative cases, suboptimal control of blood glucose levels in patients with diabetes prompted further investigation. Assessment of C-peptide levels helped determine a precise diagnosis of type 1 or type 2 diabetes, information that was pivotal in choosing treatment options and improving the outcome. These examples show that the age of the patient at the time of diagnosis of diabetes does not necessarily indicate the type of diabetes that is present. CONCLUSION: Clinicians should be aware of the importance of establishing whether patients have type 1 or type 2 diabetes mellitus and the implications of that distinction on the effectiveness of therapeutic strategies.

Journal Article↗
PubMedDate not supplied

How long can insulin therapy be avoided in the patient with type 2 diabetes mellitus by use of a combination of metformin and a sulfonylurea?

OBJECTIVE: To assess the effective longevity of combination double oral therapy before insulin or triple oral therapy is needed in patients with type 2 diabetes mellitus. METHODS: We retrospectively reviewed the outcomes of our first 100 patients with type 2 diabetes who were successfully transferred from twice-daily mixed NPH and regular insulin to a combination of metformin and a sulfonylurea. RESULTS: Of the 100 study patients, 40 had well-controlled plasma glucose (glycosylated hemoglobin levels <8.0%) with use of metformin and a sulfonylurea. Good glycemic control was achieved with triple oral therapy (a sulfonylurea, metformin, and a thiazolidinedione) in 14 patients and with a sulfonylurea, metformin, and evening-administered mixed NPH and regular insulin in 7. In addition, plasma glucose was effectively controlled with twice-daily mixed NPH and regular insulin in conjunction with metformin or a thiazolidinedione (or both) in 22 patients and with twice-daily mixed NPH and regular insulin alone in 17. The mean time (+/- standard error) from primary failure of sulfonylurea monotherapy to the time when a third hypoglycemic agent was needed was 7.9 +/- 1.1 years (95% confidence interval, 5.7 to 10.1). CONCLUSION: When oral monotherapy fails (that is, glycosylated hemoglobin values exceed 8.0%) in patients with type 2 diabetes, combination therapy with a sulfonylurea and metformin is potentially effective in maintaining glycemic control and avoiding the addition of insulin or a thiazolidinedione for a mean duration of 7.9 years.

Blood Glucose↗
PubMedDate not supplied

Improved glycemic control with use of continuous subcutaneous insulin infusion compared with multiple insulin injection therapy.

OBJECTIVE: To compare, in a long-term study, glycemic control by means of continuous subcutaneous insulin infusion (CSII or insulin pump therapy) versus multiple insulin injection therapy (MIIT) in routine clinical practice. METHODS: We identified, from a search of medical records, all active patients (N = 90) receiving CSII who had previously received MIIT. The primary objective was to compare the mean glycemic control, as documented by frequent measurements of glycosylated hemoglobin (HbA(1c)), during the 3-year period before initiation of CSII versus the mean glycemic control during the 3-year period after the first year of CSII. We included all patients for whom we had sufficient data for at least 1 year for both the pre- and post-CSII periods and only those patients who had received MIIT before CSII (N = 58). To eliminate potential biases, we excluded HbA(1c) values for the first year after initiation of CSII therapy. RESULTS: For the entire study group, the mean HbA(1c) +/- standard error for the 3-year period before insulin pump therapy (during MIIT) was 8.4 +/- 0.2% versus a mean HbA(1c) of 7.7 +/- 0.1% for the 3-year period after the first year of CSII. This 0.7% improvement in HbA(1c) was statistically significant (P = 0.001). Of the 34 patients with HbA(1c) values above 8.0% during MIIT, the mean HbA(1c) decreased from 9.2 +/- 0.2% with use of MIIT to 8.2 +/- 0.2% with CSII (P = 0.0006). In the 17 patients with HbA(1c) values above 9.0% during MIIT, the mean HbA(1c) declined from 10.0 +/- 0.3% with use of MIIT to 8.4 +/- 0.3% with CSII (P = 0.0006). CONCLUSION: We conclude that implementation of intensive insulin therapy with CSII improves glycemic control, even in patients in whom MIIT has previously been used to its maximal effect.

Blood Glucose↗
PubMedDate not supplied

Use of soy protein supplement and resultant need for increased dose of levothyroxine.

OBJECTIVE: To report a case of difficulty in achieving suppressive serum levels of thyroid hormone because of malabsorption of exogenous levothyroxine attributable to daily ingestion in close temporal relationship to the intake of a soy protein-containing food supplement. METHODS: We present the relevant history and laboratory data of the current case and provide supportive documentation from the literature. RESULTS: A 45-year-old woman who had hypothyroidism after a near-total thyroidectomy and radioactive iodine ablative therapy for papillary carcinoma of the thyroid required unusually high oral doses of levothyroxine to achieve suppressive serum levels of free thyroxine (T(4)) and thyrotropin (thyroid-stimulating hormone or TSH). She had routinely been taking a "soy cocktail" protein supplement immediately after her levothyroxine. Temporal separation of the intake of the soy protein cocktail from the administration of the levothyroxine resulted in attainment of suppressive serum levels of free T(4) and TSH with use of lower doses of levothyroxine. CONCLUSION: Administration of levothyroxine concurrently with a soy protein dietary supplement results in decreased absorption of levothyroxine and the need for higher oral doses of levothyroxine to attain therapeutic serum thyroid hormone levels.

Absorption↗