Philip R. Orlander

The effect of nonsurgical periodontal therapy on hemoglobin a1c levels in persons with type 2 diabetes and chronic periodontitis a randomized clinical trial

IMPORTANCE Chronic periodontitis, a destructive inflammatory disorder of the supporting structures of the teeth, is prevalent in patients with diabetes. Limited evidence suggests that periodontal therapy may improve glycemic control. OBJECTIVE To determine if nonsurgical periodontal treatment reduces levels of glycated hemoglobin (HbA1c) in persons with type 2 diabetes and moderate to advanced chronic periodontitis. DESIGN, SETTING, AND PARTICIPANTS The Diabetes and Periodontal Therapy Trial (DPTT), a 6-month, single-masked, multicenter, randomized clinical trial. Participants had type 2 diabetes, were taking stable doses of medications, had HbA1c levels between 7% and less than 9%, and untreated chronic periodontitis. Five hundred fourteen participants were enrolled between November 2009 and March 2012 from diabetes and dental clinics and communities affiliated with 5 academic medical centers. INTERVENTIONS The treatment group (n = 257) received scaling and root planing plus chlorhexidine oral rinse at baseline and supportive periodontal therapy at 3 and 6 months. The control group (n = 257) received no treatment for 6 months. MAIN OUTCOMES AND MEASURES Difference in change in HbA1c level from baseline between groups at 6 months. Secondary outcomes included changes in probing pocket depths, clinical attachment loss, bleeding on probing, gingival index, fasting glucose level, and Homeostasis Model Assessment (HOMA2) score. RESULTS Enrollment was stopped early because of futility. At 6 months, mean HbA1c levels in the periodontal therapy group increased 0.17% (SD, 1.0), compared with 0.11% (SD, 1.0) in the control group, with no significant difference between groups based on a linear regression model adjusting for clinical site (mean difference, -0.05% [95% CI, -0.23% to 0.12%]; P = .55). Periodontal measures improved in the treatment group compared with the control group at 6 months, with adjusted between-group differences of 0.28 mm (95% CI, 0.18 to 0.37) for probing depth, 0.25 mm (95% CI, 0.14 to 0.36) for clinical attachment loss, 13.1% (95% CI, 8.1% to 18.1%) for bleeding on probing, and 0.27 (95% CI, 0.17 to 0.37) for gingival index (P < .001 for all). CONCLUSIONS AND RELEVANCE Nonsurgical periodontal therapy did not improve glycemic control in patients with type 2 diabetes and moderate to advanced chronic periodontitis. These findings do not support the use of nonsurgical periodontal treatment in patients with diabetes for the purpose of lowering levels of HbA1c. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00997178.

The Relation of Diabetes to the Severity of Acute Myocardial Infarction and Post-Myocardial Infarction Survival in Mexican-Americans and Non-Hispanic Whites: The Corpus Christi Heart Project

The effect of diabetes on survival after myocardial infarction (MI) was examined in a prospective population-based study of individuals hospitalized with MI in a bi-ethnic community of Mexican-Americans and non-Hispanic whites. Among Mexican-Americans, 54% (331 of 610) had diabetes compared with 33% (192 of 589) of non-Hispanic whites (P < 0.001). Among those with diabetes, the prevalence of a history of a cardiac event before the index admission was significantly higher (odds ratio = 1.4, 95% confidence interval [CI] 1.1–1.8) than among nondiabetic subjects. During the index hospitalization, diabetic subjects received cardiac catheterization less frequently than did nondiabetic subjects (45.1 vs. 51.5%, P = 0.03). Diabetic subjects had lower estimated ejection fractions, and the number of coronary arteries with significant obstruction (> 75%) was higher (P < 0.001). The peak creatine phosphokinase and creatine phosphokinase myocardial isoenzyme (CK-MB) levels were similar in diabetic and nondiabetic subjects. Despite a similar infarct size, diabetic subjects had a higher incidence of congestive heart failure (relative ratio = 2.2, 95% CI 1.7–2.8), more adverse indexes of short-term and long-term prognosis, and a longer average hospital stay (12.1 vs. 8.9 days, P < 0.01). After adjustment for age, sex, and ethnicity, the cumulative risk for total mortality, over 44 months of follow-up, was 37.4% among diabetic compared with 23.3% among nondiabetic subjects (P < 0.001). Diabetic subjects had a higher 28-day case-fatality rate post-MI as well as higher long-term mortality. In conclusion, diabetic subjects have similar size infarcts compared with nondiabetic subjects, but they have a more complicated hospital course and higher total mortality post-MI. Diabetes had a similar adverse effect on post-MI mortality in both Mexican-Americans and non-Hispanic whites.

Milk–alkali syndrome is a major cause of hypercalcaemia among non‐end‐stage renal disease (non‐ESRD) inpatients

Objective  Milk–alkali syndrome, once a common cause of hypercalcaemia, is now considered rare. Our aim was to estimate the prevalence of milk–alkali syndrome among hypercalcaemic, non‐end‐stage renal disease (non‐ESRD) inpatients of a University Hospital and identify patients’ and syndrome characteristics.

Ageing and hormones

With ageing, there is a decline in hormone levels, including oestrogen, testosterone, dehydroepiandrosterone and growth hormone. Replacement of these hormones has been investigated and reviewed in this paper. There are still controversies regarding the benefits and risks of replacement therapy.

Effect of Ingested Interferon-α on β-Cell Function in Children With New-Onset Type 1 Diabetes

OBJECTIVE To evaluate the safety and efficacy of ingested human recombinant interferon-α (hrIFN-α) for preservation of β-cell function in young patients with recent-onset type 1 diabetes. RESEARCH DESIGN AND METHODS Subjects aged 3–25 years in whom type 1 diabetes was diagnosed within 6 weeks of enrollment were randomly assigned to receive ingested hrIFN-α at 5,000 or 30,000 units or placebo once daily for 1 year. The primary outcome was change in C-peptide secretion after a mixed meal. RESULTS Individuals in the placebo group (n = 30) lost 56 ± 29% of their C-peptide secretion from 0 to 12 months, expressed as area under the curve (AUC) in response to a mixed meal. In contrast, children treated with hrIFN-α lost 29 ± 54 and 48 ± 35% (for 5,000 [n = 27] and 30,000 units [n = 31], respectively, P = 0.028, ANOVA adjusted for age, baseline C-peptide AUC, and study site). Bonferroni post hoc analyses for placebo versus 5,000 units and placebo versus 30,000 units demonstrated that the overall trend was determined by the 5,000-unit treatment group. Adverse events occurred at similar rates in all treatment groups. CONCLUSIONS Ingested hrIFN-α was safe at the doses used. Patients in the 5,000-unit hrIFN-α treatment group maintained more β-cell function 1 year after study enrollment than individuals in the placebo group, whereas this effect was not observed in patients who received 30,000 units hrIFN-α. Further studies of low-dose ingested hrIFN-α in new-onset type 1 diabetes are needed to confirm this effect.

Salivary cortisol can replace free serum cortisol measurements in patients with septic shock.

BACKGROUND There is a renewed interest in adrenal function during severe sepsis. Most studies have used total serum cortisol levels; however, only free serum cortisol is biologically active. The aim of this study was to determine the validity of salivary cortisol levels as a surrogate for free serum cortisol levels during septic shock. METHODS Fifty-seven patients with septic shock were studied to determine the correlation between total serum cortisol and salivary cortisol to free serum cortisol levels. Thirty-eight patients were included in the salivary to free serum cortisol correlation. Salivary cortisol level was tested by enzyme immunoassay. Serum total cortisol, free cortisol, and cortisol-binding globulin (CBG) levels were determined by liquid chromatography-mass spectrometry, equilibrium analysis, and radioimmunoassay, respectively. RESULTS The mean ± SD age was 56.6 ± 18.5 years. Fifty-seven percent were women. APACHE (Acute Physiology and Chronic Health Evaluation) II score median was 26, Simplified Acute Physiology Score II median was 61, and Sequential Organ Failure Assessment median was 13. The correlation between salivary and free serum cortisol levels was 0.79 (95% CI, 0.63-0.89; P < .0001). The correlation between free serum cortisol and total serum cortisol levels was 0.86 (95% CI, 0.78-0.92; P < .0001). The mean ± SD free serum cortisol level was 2.27 ± 1.64 μg/dL. The mean ± SD salivary cortisol level was 2.60 ± 2.69 μg/dL. The mean ± SD total serum cortisol level was 21.56 ± 8.71 μg/dL. The mean ± SD CBG level was 23.54 ± 8.33 mg/dL. CONCLUSIONS Salivary cortisol level can be used as a surrogate of free serum cortisol level in patients with septic shock with very good correlation. Salivary cortisol testing is noninvasive, easy to perform, and can be conducted daily.

Characterization of an Aquaporin-2 Water Channel Gene Mutation Causing Partial Nephrogenic Diabetes Insipidus in a Mexican Family: Evidence of Increased Frequency of the Mutation in the Town of Origin

A Mexican family with partial congenital nephrogenic diabetes insipidus (NDI) that resulted from a mutation in the aquaporin-2 water channel (AQP2) was characterized, and the source of this rare mutation was traced to the familys town of origin in Mexico. Affected individuals with profound polyuria and polydipsia were homozygous for an autosomal recessive missense V168M mutation in the AQP2 gene. Expression in oocytes revealed that, although retained in the endoplasmic reticulum (ER) to a great extent, a considerable amount of the partially functional AQP2-V168M was expressed at the plasma membrane, and that its ER retention was less than AQP2-T126M, a functional mutant in severe recessive NDI. None of the affected AQP2-V168M individuals had neurologic deficits, which also suggested a milder form of the disease. The homozygous individuals reported subjective improvement in polyuria and polydipsia with the use of dDAVP (1-desamino-8-D-arginine-vasopressin). When clinically tested, infusion of dDAVP at variable doses produced a partial increase in the urinary osmolality in homozygous individuals and decreased their water intake. Heterozygotes were unaffected when compared with controls. Samples were obtained from the population of the Mexican town of origin of the family; 30% of the population was heterozygous for the V168M AQP2 mutation and 1% was homozygous for the mutation. The high frequency of this rare mutation in the town provides evidence for an important health care problem in the village with consequences for future generations.

Calcium carbonate toxicity: The updated milk-alkali syndrome; report of 3 cases and review of the literature

OBJECTIVE To describe 3 patients with calcium carbonate-induced hypercalcemia and gain insights into the cause and management of the milk-alkali syndrome. METHODS We report the clinical and laboratory data in 3 patients who presented with severe hypercalcemia (corrected serum calcium > or = 14 mg/dL) and review the pertinent literature on milk-alkali syndrome. RESULTS The 3 patients had acute renal insufficiency, relative metabolic alkalosis, and low parathyroid hormone (PTH), PTH-related peptide, and 1,25-dihydroxyvitamin D concentrations. No malignant lesion was found. Treatment included aggressive hydration and varied amounts of furosemide. The 2 patients with the higher serum calcium concentrations received pamidronate intravenously (60 and 30 mg, respectively), which caused severe hypocalcemia. Of the 3 patients, 2 were ingesting acceptable doses of elemental calcium (1 g and 2 g daily, respectively) in the form of calcium carbonate. In addition to our highlighted cases, we review the history, classification, pathophysiologic features, and treatment of milk-alkali syndrome and summarize the cases reported from early 1995 to November 2003. CONCLUSION Milk-alkali syndrome may be a common cause of unexplained hypercalcemia and can be precipitated by small amounts of orally ingested calcium carbonate in susceptible persons. Treatment with hydration, furosemide, and discontinuation of the calcium and vitamin D source is adequate. Pamidronate treatment is associated with considerable risk for hypocalcemia, even in cases of initially severe hypercalcemia.

Ingested IFN-α Preserves Residual β Cell Function in Type 1 Diabetes

Type 1 diabetes mellitus is a chronic disorder that presumably results from an autoimmune destruction of the insulin-producing pancreatic beta cells. The therapeutic potential of interventions aimed at preventing type 1 diabetes can be assessed in newly diagnosed patients. Because there is a historical experience of a low incidence of spontaneous remission in type 1 diabetes mellitus, interventions preserving beta cell function have been used to identify positive therapeutic outcomes. We treated 10 newly diagnosed type 1 diabetes patients with 30,000 IU ingested interferon-alpha (IFN-alpha) within 1 month of diagnosis and examined the difference between baseline and Sustacal-induced (Mead Johnson Nutritionals, Evansville, IN) C-peptide responses, respectively, at 0, 3, 6, 9, and 12 months. Eight of the ten patients showed preserved beta cell function, with at least a 30% increase in stimulated C-peptide levels at 0, 3, 6, 9, and 12 months after initiation of treatment. There was no discernible chemical or clinical toxicity associated with ingested IFN-alpha. Our results support the potential of ingested IFN-alpha to preserve residual beta cell function in recent onset type 1 diabetes mellitus and the testing of IFN-alpha in a placebo-controlled trial.

Ingested IFN-alpha preserves residual beta cell function in type 1 diabetes.

Type 1 diabetes mellitus is a chronic disorder that presumably results from an autoimmune destruction of the insulin-producing pancreatic beta cells. The therapeutic potential of interventions aimed at preventing type 1 diabetes can be assessed in newly diagnosed patients. Because there is a historical experience of a low incidence of spontaneous remission in type 1 diabetes mellitus, interventions preserving beta cell function have been used to identify positive therapeutic outcomes. We treated 10 newly diagnosed type 1 diabetes patients with 30,000 IU ingested interferon-alpha (IFN-alpha) within 1 month of diagnosis and examined the difference between baseline and Sustacal-induced (Mead Johnson Nutritionals, Evansville, IN) C-peptide responses, respectively, at 0, 3, 6, 9, and 12 months. Eight of the ten patients showed preserved beta cell function, with at least a 30% increase in stimulated C-peptide levels at 0, 3, 6, 9, and 12 months after initiation of treatment. There was no discernible chemical or clinical toxicity associated with ingested IFN-alpha. Our results support the potential of ingested IFN-alpha to preserve residual beta cell function in recent onset type 1 diabetes mellitus and the testing of IFN-alpha in a placebo-controlled trial.