Prosthetic Abutment Height is a Key Factor in Peri-implant Marginal Bone Loss.

In this study, we analyzed the influence of prosthetic abutment height on marginal bone loss (MBL) around implants in the posterior maxilla. In this retrospective cohort study, the radiographically determined MBL was related to the height of the abutments of internal conical connection implants at 6 and 18 months post-loading. Data were gathered on age, sex, bone substratum, smoking habit, history of periodontitis, and prosthetic features, among other variables. A linear mixed model was used for statistical analysis. The study included 131 patients receiving 315 implants. MBL rates at 6 and 18 months were mainly affected by the abutment height but were also significantly influenced by the bone substratum, periodontitis, and smoking habit. MBL rates were higher for prosthetic abutment < 2 mm vs. ≥ 2 mm, for periodontal vs. non-periodontal patients, for grafted vs. pristine bone, and for a heavier smoking habit. The abutment height is a key factor in MBL. MBL rates followed a non-linear trend, with a greater MBL rate during the first 6 months post-loading than during the next 12 months.

Clinical approach to the patient with diabetes mellitus and very high insulin requirements.

A number of patients with diabetes require very high (> 2 Ukg⁻¹ day⁻¹), or extremely high (> 3 Ukg⁻¹ day⁻¹), insulin doses for the management of their hyperglycemia. Unfortunately, many of the physicians who treat these patients limit themselves to prescribing ever higher doses of insulin, without questioning why. Furthermore, when the insulin requirements get to be extreme, demanding an explanation, clinicians are frequently lost in a sea of literature where there is not a single paper dealing with this problem systematically. A systematic approach to the evaluation of these patients is necessary to facilitate an appropriate diagnosis, select the most reasonable therapy, and hopefully improve the long-term outcome of these patients. This manuscript intends to provide the clinician with a review of the literature pertinent for the differential diagnosis, work-up, and management of these patients. We will review the definitions of insulin sensitivity during normality, the various degrees or categories of insulin resistance, and the expected insulin requirements during each of these states. Subsequently, we propose a simple alphabetic mnemonic approach to help remember the differential diagnosis, and a clinical algorithm to help guide the work-up of these patients. Lastly, we briefly discuss general management considerations in these conditions.

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.

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.

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.

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.

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.

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.

[Frequency of anti-Toxoplasma gondii antibodies in cats from Valdivia city, Chile]. / Frecuencia de anticuerpos anti Toxoplasma gondii en gatos de la ciudad de Valdivia, Chile.

Toxoplasmosis is a parasitic zoonosis. The importance of the cat as related to this parasitosis lies in the fact that it is not only the definite host of the parasite, but responsible for its dissemination through the release of oocysts, which subsequently infect both humans and other animals. The objective of this study was to determine the serological prevalence of Toxoplasma gondii in the feline population of the city of Valdivia (Chile) and to establish the possible epidemiological implications of this prevalence. With these goals in mind the technique of indirect immunofluorescence was implemented to detect anti- T. gondii species--specific IgG. Blood samples from 97 cats (selected using a directed sampling process) from different sectors of Valdivia were collected. The sample included 46 males and 51 females of different ages, Positive and negative control sera obtained from de United States were used to verify the results, observed by UV microscopy. The anti-feline IgG antibody was used as directed by the manufacturer (Sigma). Of the 97 selected cats, 32 were found to be positive with a titre higher than 1:4, a prevalence of 33.0%. The number of infected males as compared to the number of infected females was found to be statistically insignificant, using the chi-square analysis with p less than 0.1. In contrast, a definite correlation between age and seropositivity was found; infection levels were higher in older animals. These results are consistent with those obtained in different studies on this topic that have been performed in different parts of the world. However, they would seem to be in conflict with other, similar studies that have been done recently in Chile; this may be due to the fact that the cats selected for this study were exposed to different climatic conditions than those examined in previous works. In conclusion, it has been determined that in Valdivia exist cats infected by T. gondii, which indicate the presence of the necessary epidemiological conditions for the persistence of this parasitic cycle and the source of infection for humans and other animals.

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.

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.