Periodontitis Risk Factors in Adults with Cystic Fibrosis: A pilot study.

Purpose Individuals with cystic fibrosis (CF) present with multiple condition-specific risk factors for periodontitis including CF-related diabetes, chronic inhaled treatments that induce xerostomia, and increased systemic inflammation because of frequent lung infections. General factors like age, oral hygiene, and diet may also contribute to the risk of periodontitis. However the relative importance of these specific risk factors and periodontitis in individuals with CF has not yet been evaluated. The purpose of this pilot study was to assess the associations between CF condition-specific and general risk factors and the prevalence of periodontitis in adults with CF.Methods This cross-sectional pilot study was designed to assess a multifactorial model of periodontitis risk factors in a population in adults with CF who were recruited from the University of Washington Adult CF center. Periodontitis was defined using the Centers for Disease Control and Prevention and the American Academy of Periodontology (CDC/AAP) case definition. Risk factors included condition-specific and general factors. Differences between participants with moderate/severe periodontitis and those with no/mild periodontitis was assessed using the Mann-Whitney test, the Fisher's exact test, and the exact chi-square test (α=0.05).Results Thirty-two participants were enrolled. Twenty-eight percent of the participants had moderate periodontitis, 72% had no/mild periodontitis; none of the participants had severe periodontitis. There were no significant differences in condition-specific factors between between the two study groups. Participants with moderate periodontitis were older (p=0.028) and reported daily flossing in higher proportions than those with no/mild periodontitis (p=0.023).Conclusions The findings from this pilot study suggest that future research is needed to determine whether sociodemographic and other general risk factors are more important contributors to periodontitis risk than CF-specific factors.

Continuous Glucose Monitoring and Use of Alternative Markers To Assess Glycemia in Chronic Kidney Disease.

OBJECTIVE: In chronic kidney disease, glycated albumin and fructosamine have been postulated to be better biomarkers of glycemic control than HbA1c. We evaluated the accuracy, variability, and covariate bias of three biomarkers (HbA1c, glycated albumin, and fructosamine) compared with continuous glucose monitoring (CGM)-derived measurement of glycemia across estimated glomerular filtration rate (eGFR) in type 2 diabetes. RESEARCH DESIGN AND METHODS: A prospective cohort study was conducted of 104 participants with type 2 diabetes, 80 with eGFR <60 mL/min/1.73 m2 (not treated with dialysis) and 24 frequency-matched control subjects with eGFR ≥60 mL/min/1.73 m2. Participants wore a blinded CGM for two 6-day periods separated by 2 weeks, with blood and urine collected at the end of each CGM period. HbA1c, glycated albumin, and fructosamine were measured by high-performance liquid chromatographic, enzymatic, and colorimetric nitroblue tetrazolium methods, respectively. RESULTS: Within-person biomarker values were strongly correlated between the two CGM periods (r = 0.92-0.95), although no marker fully captured the within-person variability of mean CGM glucose. All markers were similarly correlated with mean CGM glucose (r = 0.71-77). Compared with mean CGM glucose, glycated albumin and fructosamine were significantly biased by age, BMI, serum iron concentration, transferrin saturation, and albuminuria; HbA1c was underestimated in those with albuminuria. CONCLUSIONS: Glycated albumin and fructosamine were not less variable than HbA1c at a given mean CGM glucose level, with several additional sources of bias. These results support measuring HbA1c to monitor trends in glycemia among patients with eGFR <60 mL/min/1.73 m2. Direct measurements of glucose are necessary to capture short-term variability.

Glucose time in range and peripheral neuropathy in type 2 diabetes mellitus and chronic kidney disease.

​OBJECTIVE: Compared with hemoglobin A1c (HbA1c), continuous glucose monitoring (CGM) may better capture risk of diabetes complications in patients with chronic kidney disease (CKD), including diabetic peripheral neuropathy (DPN). We hypothesized that glucose time in range (TIR), measured by CGM, is associated with DPN symptoms among participants with type 2 diabetes mellitus (type 2 DM) and moderate-to-severe CKD. ​RESEARCH DESIGN AND METHODS: We enrolled 105 people with type 2 DM treated with insulin or sulfonylurea, 81 participants with CKD (estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2) and 24 matched control participants with eGFR ≥60 mL/min/1.73 m2. Each participant wore a CGM for two 6-day periods. Calculated glycemic measures included TIR (glucose 70-180 mg/dL) and glucose management indicator (GMI). DPN symptoms were assessed using the Michigan Neuropathy Screening Instrument (MNSI) questionnaire, with a positive MNSI score defined as ≥2 symptoms. ​RESULTS: Participants with CKD had a mean age of 68 years, diabetes duration 20 years, eGFR 38 mL/min/1.73 m2 and HbA1c 7.8%, 61 mmol/mol. Sixty-two participants reported ≥2 DPN symptoms, 51 (63%) with CKD and 11 (46%) controls. Less TIR and higher GMI were associated with higher risk of MNSI questionnaire score ≥2 (OR 1.25 (95% CI 1.02 to 1.52) per 10% lower TIR, and OR 1.79 (95% CI 1.05 to 3.04) per 1% higher GMI, adjusting for age, gender and race). Similar results were observed when analyses were restricted to participants with CKD. In contrast, there was no significant association of HbA1c with DPN symptoms. ​CONCLUSIONS: Symptoms of DPN were common among participants with long-standing type 2 DM and CKD. Lower TIR and higher GMI were associated with DPN symptoms.

A PROMIS Measure of Neuropathic Pain Quality.

OBJECTIVES: Neuropathic pain (NP) is a consequence of many chronic conditions. This study aimed to develop an unidimensional NP scale with scores that represent levels of NP and distinguish between individuals with NP and non-NP conditions. METHODS: A candidate item pool of 42 pain quality descriptors was administered to participants with osteoarthritis, rheumatoid arthritis, diabetic neuropathy, and cancer chemotherapy-induced peripheral neuropathy. A subset of pain quality descriptors (items) that best distinguished between participants with and those without NP conditions were identified. Dimensionality of pain descriptors was evaluated in a development sample and cross-validated in a holdout sample. Item responses were calibrated using an item response theory model, and scores were generated on a T-score metric. NP scale scores were evaluated in terms of the reliability, validity, and ability to distinguish between participants with and without conditions typically associated with NP. RESULTS: Of the 42 initial items, 5 were identified for the Patient-Reported Outcome Measurement Information System (PROMIS) Neuropathic Pain Quality Scale. T scores exhibited good discriminatory ability on the basis of receiver-operator characteristic analysis. Score thresholds that optimize sensitivity and specificity were identified. Construct, criterion, and discriminant validity, and reliability of scale scores were supported. CONCLUSIONS: The five-item Patient-Reported Outcome Measurement Information System (PROMIS PQ-Neuro) Neuropathic Pain Quality Scale is a short and practical measure that can be used to identify patients more likely to have NP and to distinguish levels of NP. The data collected will support future research that targets other unidimensional pain quality domains (e.g., nociceptive pain).

American Association of Clinical Endocrinologists and American College of Endocrinology Protocol for Standardized Production of Clinical Practice Guidelines, Algorithms, and Checklists--2014 Update and the AACe G4G Program.

In 2010, the American Association of Clinical Endocrinologists (AACE) published an update to the original 2004 guidelines. This update hybridized strict evidence-based medicine methods with subjective factors and improved the efficiency of clinical practice guidelines (CPG) production, clinical applicability, and usefulness. Current and persistent shortcomings involving suboptimal implementation and protracted development timelines are addressed in the current 2014 update. The major advances include 1) formulation of an organizational educational strategy, represented by the AACE Council on Education, to address relevant teaching and decision-making tools for clinical endocrinologists, and to generate specific clinical questions to drive CPG, clinical algorithm (CA), and clinical checklist (CC) development; 2) creation and prioritization of printed and online CAs and CCs with a supporting evidence base; 3) focus on clinically relevant and question-oriented topics; 4) utilization of "cascades," where there can be more than 1 recommendation for 1 clinical question; and 5) incorporation of performance metrics to validate, optimize, and effectively update CPG, CAs, and CCs. Efforts continue to translate these clinical tools to electronic formats that can be integrated into a paperless healthcare delivery system, as well as applying them to diverse clinical settings by incorporating transcultural factors.

Advanced meter features improve postprandial and paired self-monitoring of blood glucose in individuals with diabetes: results of the Actions with the CONTOUR Blood Glucose Meter and Behaviors in Frequent Testers (ACT) study.

BACKGROUND: This study evaluated whether education and use of the advanced meter features of the CONTOUR(®) (Bayer HealthCare LLC, Diabetes Care, Tarrytown, NY) blood glucose monitoring system (BGMS) affect the frequency and pattern of blood glucose testing in insulin-using subjects with diabetes who routinely perform self-monitoring of blood glucose (SMBG). SUBJECTS AND METHODS: Insulin-using subjects with type 1 or type 2 diabetes were enrolled in this 6-month, multicenter, prospective study and randomized to one of two groups. The basic meter features group (BMF group) received basic instruction in the use of the BGMS, whereas the advanced meter features group (AMF group) also received training in the use of advanced features, including the meal marker and audible reminder, and were instructed to use these features. Both groups received education on the importance of postprandial testing. RESULTS: The AMF group (n=105) had significantly greater average weekly postprandial blood glucose testing than the BMF group (n=106) at each follow-up visit (P<0.001) and significantly increased the frequency of paired blood glucose testing (P<0.001) as well. In both groups, glycated hemoglobin decreased significantly as postprandial testing frequency increased (P<0.05). Subject reports indicated that use of advanced features made postmeal SMBG considerably easier to remember, helped them better understand how to make decisions on their own, and increased their confidence in meal choices. CONCLUSIONS: Study findings showed that advanced features of the CONTOUR BGMS increased structured testing as measured by postprandial and paired SMBG and were perceived as useful by patients.

Motherhood, apple pie, hemoglobin A(1C), and the DCCT.

OBJECTIVE: To review recent literature on the limitations of hemoglobin A(1c) (HbA(1c)) as a marker of glycemic control. METHODS: English-language literature published between 1985 and 2011 was reviewed specific to analyses of major trials relating glycemic control to complications of diabetes mellitus, as expressed through HbA(1c) as a marker of glycemic control. RESULTS: HbA(1c) has been accepted as the most fundamental biomarker in diabetes, if not all of medicine, as it clearly predicts risk for diabetes-related complications. What is not generally appreciated is that HbA(1c) is a crude marker of glycemia with many limitations. It is now accepted that HbA(1c) does not reflect mean glucose for many people, and even for those it does, any level could represent a wide range of glycemia. While we have learned HbA(1c) is not a perfect biomarker, we also know that in the Diabetes Control and Complications Trial, HbA(1c) could only explain 11% of the variation in retinopathy risk between the conventional and intensive therapy groups. This important finding suggests that other glycemic and nonglycemic factors may be responsible for the pathogenesis of diabetes-related complications. One candidate is glycemic variability, which must be differentiated from postprandial hyperglycemia since hypoglycemia can also result in inflammatory activation. Importantly, although it is clear that in insulin-requiring patients glycemic variability is associated with hypoglycemia, we require a definitive prospective trial to confirm glycemic variability's association with one or more vascular complications. CONCLUSIONS: What is abundantly clear is that the HbA(1c) message, as we know it, is too simplistic. While certain wholesome concepts such as motherhood and apple pie are accepted by all, the HbA(1c) message may be more complex than originally appreciated, and it may be time to reevaluate our most basic premise in diabetes.

Prevalence and correlates of dietary supplement use in individuals with diabetes mellitus at an academic diabetes care clinic.

OBJECTIVES: This study sought to describe the prevalence of supplement use by those with diabetes mellitus receiving care at an academic outpatient diabetes care center and to identify any association of supplement use with glycemic control. METHODS: This study is based on a retrospective audit of provider-verified and patient-self-reported medication and supplement use by adults with diabetes at the University of Washington Diabetes Care Center during four 2-week periods from fall 2006 through summer 2007 (1 period per season). RESULTS: Verified medication and supplement histories for 459 adults demonstrated a per-person average use of 7 ± 4.1 prescription medicines and 0.4 ± 0.9 over-the-counter medicines daily, with 55% using some form of vitamin, mineral, or nonvitamin-nonmineral supplement on a daily basis. The rate of nonvitamin-nonmineral use was nearly twice that for type 2 diabetes mellitus as for type 1 diabetes mellitus (39.3% vs 20.3%), and A1c was lower in those using any supplement compared to those not using supplements. Vitamin use was associated with reduced A1c; however, this relationship did not hold at A1c < 7.0%. CONCLUSIONS: The findings highlight the prevalence of supplement use in diabetes mellitus and association of supplement use with improved glycemic control. Findings are limited by the retrospective design.

American Association of Clinical Endocrinologists Protocol for Standardized Production of Clinical Practice Guidelines--2010 update.

In 2004, the American Association of Clinical Endocrinologists (AACE) published the "Protocol for Standardized Production of Clinical Practice Guidelines," which was to be implemented in forthcoming clinical practice guidelines (CPG). This protocol formally incorporated subjective factors and evidence-based medicine (EBM) methods that tightly mapped evidence levels to recommendation grades. A uniform publication template and multilevel review process were also outlined. Seven CPG have been subsequently published with use of this 2004 AACE protocol. Recently, growing concerns about the usefulness of CPG have been raised. The purposes of this report are to address shortcomings of the 2004 AACE protocol and to present an updated 2010 AACE protocol for CPG development. AACE CPG are developed without any industry involvement. Multiplicities of interests among writers and reviewers that might compromise the usefulness of CPG are avoided. Three major goals are to (1) balance transparently the effect of rigid quantitative EBM methods with subjective factors, (2) create a less onerous, less time-consuming, and less costly CPG production process, and (3) introduce an electronic implementation component. The updated 2010 AACE protocol emphasizes "informed judgment" and hybridizes EBM descriptors (study design type), qualifiers (study flaws), and subjective factors (such as risk, cost, and relevance). In addition, by focusing on more specific topics and clinical questions, the expert evaluation and multilevel review process is more transparent and expeditious. Lastly, the final recommendations are linked to a new electronic implementation feature.

One-year weight losses in the Look AHEAD study: factors associated with success.

This report provides a further analysis of the first year weight losses in the Look AHEAD (Action for Health in Diabetes) study and identifies factors associated with success. Participants were a total of 5,145 men and women with type 2 diabetes who were recruited at 16 sites and randomly assigned to an intensive lifestyle intervention (ILI) or a control condition, Diabetes Support and Education (DSE). During year 1, participants in ILI received comprehensive diet and physical activity counseling in a total of 42 group and individual sessions, compared with three educational sessions for DSE participants. As reported previously, at the end of the year, ILI participants lost 8.6% of initial weight, compared to 0.7% for DSE (P < 0.001). Within the ILI group, all racial/ethnic groups achieved clinically significant weight losses (>5.5%), although there were significant differences among groups. For the year, ILI participants attended an average of 35.4 treatment sessions and reported exercising a mean of 136.6 min/week and consuming a total of 360.9 meal replacement products. Greater self-reported physical activity was the strongest correlate of weight loss, followed by treatment attendance and consumption of meal replacements. The use of orlistat, during the second half of the year, increased weight loss only marginally in those ILI participants who had lost <5% of initial weight during the first 6 months and chose to take the medication thereafter as a toolbox option. The lifestyle intervention was clinically effective in all subsets of an ethnically and demographically diverse population.

Immunosuppressive agents: effects on glucose and lipid metabolism.

Immunosuppressive therapies are critical elements in successful organ transplantation. Although immunosuppressant drugs are essential in preventing graft rejection and graft maintenance after transplantation, their use is complicated by adverse effects, many being detrimental to graft and even patient long-term survival. Commonly used agents are associated with dysregulated glucose metabolism and dyslipidemia. This article focuses on the effects of immunosuppressive agents on glucose and lipid metabolism. Adrenal effects of these drugs, where known, also are discussed.

Diabetic neuropathy, the great masquerader: truncal neuropathy manifesting as abdominal pseudohernia.

OBJECTIVE: To describe a patient with diabetic truncal neuropathy and suggest a helpful diagnostic approach to this entity. METHODS: We present a case report, with a focus on physical, computed tomographic, and electromyographic findings. RESULTS: Because of an extensive differential diagnosis, diabetic truncal neuropathy is a rarely recognized and often misdiagnosed condition in patients with diabetes mellitus. In a 55-year-old man with a 13-year history of diabetes but no retinopathy, vasculopathy, or nephropathy, pain and a visible bulge in the left lower abdominal quadrant prompted radiographic assessment of the abdomen. A computed tomographic scan of the abdomen disclosed no mass but a weakening of the abdominal musculature suggestive of a pseudohernia. Subsequent electromyography showed evidence of polyradicular neuropathy. The patient was given treatment for pain control, and the pseudohernia resolved within 1 year. CONCLUSION: In patients with diabetes who have a painful abdominal mass, the potential presence of a diabetic truncal neuropathy should be considered.

Treating diabetes using oral agents.

Since the development and release of sulfonylureas for the treatment of T2DM, additional oral glycemic control agents with different mechanisms of action have allowed for more flexibility in targeting drug to patient. Based on available evidence, metformin monotherapy is preferred for the vast majority of T2DM patients who are overweight or obese. Combination therapy has further improved glycemic control. However, limitations in use, including the challenges of side effects, to that of secondary oral agent failure will inevitably occur over time. These challenges leave ample room for the development of agents that address the pathophysiology not only of treating insulin resistance and decreasing insulin production but also of preventing or delaying the development of diabetes in populations at risk.

Management of patients on chronic glucocorticoid therapy: an endocrine perspective.

Glucocorticoids continue to be a potent therapeutic tool for various medical conditions; however, their medication side effects pose challenges. Steroid diabetes is treated primarily with prandial insulin, either regular or the rapid insulins (lispro or aspart). Intermediate insulin is indicated less frequently, for fasting hyperglycemia. Osteoporosis is the most debilitating of potential glucocorticoid side effects, with bisphosphonates the mainstay of prevention and treatment. Dyslipidemia can range from mild to significant, but it responds to therapy similar to that of nonglucocorticoid-induced lipid disorders. Glucocorticoid-induced adrenal withdrawal syndrome can occur even with short courses of longer-acting glucocorticoid therapy, but it responds to adjustment of glucocorticoid dose. When tapering down to near-physiologic dose, pituitary-adrenal axis responsiveness should be checked before discontinuing steroid use.

The rationale and management of hyperglycemia for in-patients with cardiovascular disease: time for change.

There is increasing evidence that aggressive glycemic control for patients admitted into the hospital improves clinical outcomes, especially for patients with cardiovascular disease. There appear to be a variety of mechanisms for this. Although hyperglycemia has been shown to result in poor wound healing and more infectious complications, especially after cardiac surgical procedures, what has become clear is that the treatment of hyperglycemia with i.v. glucose, insulin, and potassium (GIK) results in better clinical outcomes even in patients without diabetes. The mechanisms for this are not year clear, but could be related to the insulin administration, perhaps due to suppression of various cytokines or free fatty acids. The practical use of insulin in these patients requires basic understanding of the use of both i.v. and s.c. insulin. Although there are several appropriate options for both of these routes of administration, it is critical that all caregivers involved in this population's care are knowledgeable about insulin strategies.