Showing papers in "Diabetes Care in 2010"
TL;DR: The Brazilian study provided evidence that adverse perinatal outcomes are associated with levels of maternal glycemia below those diagnostic of GDM by American Diabetes Association or World Health Organization criteria, however, the results were potentially confounded by the treatment of G DM.
Abstract: In the accompanying comment letter (1), Weinert summarizes published data from the Brazilian Gestational Diabetes Study (2) and comments on applying International Association of Diabetes and Pregnancy Study Groups (IADPSG) Consensus Panel recommendations (3) for the diagnosis of gestational diabetes mellitus (GDM) to that cohort
The Brazilian study provided evidence that adverse perinatal outcomes are associated with levels of maternal glycemia below those diagnostic of GDM by American Diabetes Association or World Health Organization criteria However, the results were potentially confounded by the treatment of GDM It did find that women with GDM were at increased risk for some …
3,969 citations
TL;DR: These standards of care are intended to provide clinicians, patients, researchers, payors, and other interested individuals with the components of diabetes care, general treatment goals, and tools to evaluate the quality of care.
Abstract: D iabetes is a chronic illness that requires continuing medical care and ongoing patient self-management education and support to prevent acute complications and to reduce the risk of long-term complications. Diabetes care is complex and requires that many issues, beyond glycemic control, be addressed. A large body of evidence exists that supports a range of interventions to improve diabetes outcomes. These standards of care are intended to provide clinicians, patients, researchers, payors, and other interested individuals with the components of diabetes care, general treatment goals, and tools to evaluate the quality of care. While individual preferences, comorbidities, and other patient factors may require modification of goals, targets that are desirable for most patients with diabetes are provided. These standards are not intended to preclude clinical judgment or more extensive evaluation and management of the patient by other specialists as needed. For more detailed information about management of diabetes, refer to references 1–3. The recommendations included are screening, diagnostic, and therapeutic actions that are known or believed to favorably affect health outcomes of patients with diabetes. A grading system (Table 1), developed by the American Diabetes Association (ADA) and modeled after existing methods, was used to clarify and codify the evidence that forms the basis for the recommendations. The level of evidence that supports each recommendation is listed after each recommendation using the letters A, B, C, or E. These standards of care are revised annually by the ADA multidisciplinary Professional Practice Committee, and new evidence is incorporated. Members of the Professional Practice Committee and their disclosed conflicts of interest are listed in the Introduction. Subsequently, as with all position statements, the standards of care are reviewed and approved by the Executive Committee of ADA’s Board of Directors.
3,405 citations
TL;DR: A joint meeting of the 19th annual Diabetic Neuropathy Study Group of the European Association for the Study of Diabetes (NEURODIAB) and the 8th International Symposium on Diabetes in Toronto, Canada, 13-18 October 2009, expert panels were convened to provide updates on classification, definitions, diagnostic criteria, and treatments of diabetic peripheral neuropathies as mentioned in this paper.
Abstract: Preceding the joint meeting of the 19th annual Diabetic Neuropathy Study Group of the European Association for the Study of Diabetes (NEURODIAB) and the 8th International Symposium on Diabetic Neuropathy in Toronto, Canada, 13-18 October 2009, expert panels were convened to provide updates on classification, definitions, diagnostic criteria, and treatments of diabetic peripheral neuropathies (DPNs), autonomic neuropathy, painful DPNs, and structural alterations in DPNs.
1,922 citations
TL;DR: A consensus statement of experts assembled jointly by the American Diabetes Association and the American Cancer Society reviews the state of science concerning the association between diabetes and cancer incidence or prognosis and whether diabetes treatments influence risk of cancer or cancer prognosis.
Abstract: Epidemiologic evidence suggests that cancer incidence is associated with diabetes as well as certain diabetes risk factors and diabetes treatments. This consensus statement of experts assembled jointly by the American Diabetes Association and the American Cancer Society reviews the state of science concerning 1) the association between diabetes and cancer incidence or prognosis, 2) risk factors common to both diabetes and cancer, 3) possible biologic links between diabetes and cancer risk, and 4) whether diabetes treatments influence risk of cancer or cancer prognosis. In addition, key unanswered questions for future research are posed.
1,790 citations
TL;DR: Data from 11 studies comparing SSB intake in the highest to lowest quantiles in relation to risk of metabolic syndrome and type 2 diabetes provide empirical evidence that intake of SSBs should be limited to reduce obesity-related risk of chronic metabolic diseases.
Abstract: OBJECTIVE — Consumption of sugar-sweetened beverages (SSBs), which include soft drinks, fruit drinks, iced tea, and energy and vitamin water drinks has risen across the globe. Regular consumption of SSBs has been associated with weight gain and risk of overweight and obesity, but the role of SSBs in the development of related chronic metabolic diseases, such as metabolic syndrome and type 2 diabetes, has not been quantitatively reviewed. RESEARCH DESIGN AND METHODS — We searched the MEDLINE database up to May 2010 for prospective cohort studies of SSB intake and risk of metabolic syndrome and type 2 diabetes. We identified 11 studies (three for metabolic syndrome and eight for type 2 diabetes) for inclusion in a random-effects meta-analysis comparing SSB intake in the highest to lowest quantiles in relation to risk of metabolic syndrome and type 2 diabetes. RESULTS — Based on data from these studies, including 310,819 participants and 15,043 cases of type 2 diabetes, individuals in the highest quantile of SSB intake (most often 1–2 servings/day) had a 26% greater risk of developing type 2 diabetes than those in the lowest quantile (none or 1 serving/month) (relative risk [RR] 1.26 [95% CI 1.12–1.41]). Among studies evaluating metabolic syndrome, including 19,431 participants and 5,803 cases, the pooled RR was 1.20 [1.02–1.42]. CONCLUSIONS — In addition to weight gain, higher consumption of SSBs is associated with development of metabolic syndrome and type 2 diabetes. These data provide empirical evidence that intake of SSBs should be limited to reduce obesity-related risk of chronic metabolic diseases. Diabetes Care 33:2477–2483, 2010
1,708 citations
TL;DR: The benefits of physical training are discussed, along with recommendations for varying activities, PA-associated blood glucose management, diabetes prevention, gestational diabetes mellitus, and safe and effective practices for PA with diabetes-related complications.
Abstract: Although physical activity (PA) is a key element in the prevention and management of type 2 diabetes, many with this chronic disease do not become or remain regularly active. High-quality studies establishing the importance of exercise and fitness in diabetes were lacking until recently, but it is now well established that participation in regular PA improves blood glucose control and can prevent or delay type 2 diabetes, along with positively affecting lipids, blood pressure, cardiovascular events, mortality, and quality of life. Structured interventions combining PA and modest weight loss have been shown to lower type 2 diabetes risk by up to 58% in high-risk populations. Most benefits of PA on diabetes management are realized through acute and chronic improvements in insulin action, accomplished with both aerobic and resistance training. The benefits of physical training are discussed, along with recommendations for varying activities, PA-associated blood glucose management, diabetes prevention, gestational diabetes mellitus, and safe and effective practices for PA with diabetes-related complications.
1,635 citations
TL;DR: Quality of sleep consistently and significantly predict the risk of the development of type 2 diabetes and the mechanisms underlying this relation may differ between short and long sleepers.
Abstract: OBJECTIVE - To assess the relationship between habitual sleep disturbances and the incidence of type 2 diabetes and to obtain an estimate of the risk.
RESEARCH DESIGN AND METHODS - We conducted a systematic search of publications using MEDLINE (1955-April 2009), EMBASE, and the Cochrane Library and manual searches Without language restrictions. We included studies if they were prospective with follow-up >3 years and had an assessment of sleep disturbances at baseline and incidence of type 2 diabetes. We recorded several characteristics for each study. We extracted quantity and quality of sleep, how they were assessed, and incident cases defined with different validated methods. We extracted relative risks (RRs) and 95% Cl and pooled them using random-effects models. We performed sensitivity analysis and assessed heterogeneity and publication bias.
RESULTS - we included 10 Studies (13 independent cohort Samples; 107,756 male and female participants, follow-up range 4.2-32 years, and 3,586 incident cases Of type 2 diabetes). In pooled analyses, quantity and quality of sleep predicted the risk of development Of type 2 diabetes. For short duration of sleep (: 8-9 h/night), the RR was 1.48 (1.13-1.96, P = 0.005); for difficulty in initiating sleep, the RR was 1.57 (1.25-1.97, P < 0.0001); and for difficulty in maintaining sleep, the RR was 1.84 (1.39-2.43, P < 0.0001).
CONCLUSIONS - Quantity and quality of sleep consistently and significantly predict the risk Of the development Of type 2 diabetes. The mechanisms Underlying this relation may differ between short and long sleepers.
1,299 citations
TL;DR: The Brazilian study provided evidence that adverse perinatal outcomes are associated with levels of maternal glycemia below those diagnostic of GDM by American Diabetes Association or World Health Organization criteria, however, the results were potentially confounded by the treatment of G DM.
Abstract: In the accompanying comment letter (1), Weinert summarizes published data from the Brazilian Gestational Diabetes Study (2) and comments on applying International Association of Diabetes and Pregnancy Study Groups (IADPSG) Consensus Panel recommendations (3) for the diagnosis of gestational diabetes mellitus (GDM) to that cohort.
The Brazilian study provided evidence that adverse perinatal outcomes are associated with levels of maternal glycemia below those diagnostic of GDM by American Diabetes Association or World Health Organization criteria. However, the results were potentially confounded by the treatment of GDM. It did find that women with GDM were at increased risk for some …
1,265 citations
TL;DR: This study suggests VAI is a valuable indicator of “visceral adipose function” and insulin sensitivity, and its increase is strongly associated with cardiometabolic risk.
Abstract: Objective To individuate a novel sex-specific index, based on waist circumference, BMI, triglycerides, and HDL cholesterol, indirectly expressing visceral fat function. Research design and methods Visceral adiposity index (VAI) was first modeled on 315 nonobese healthy subjects. Using two multiple logistic regression models, VAI was retrospectively validated in 1,498 primary care patients in comparison to classical cardio- and cerebrovascular risk factors. Results All components of metabolic syndrome increased significantly across VAI quintiles. VAI was independently associated with both cardiovascular (odd ratio [OR] 2.45; 95% CI 1.52-3.95; P Conclusions Our study suggests VAI is a valuable indicator of "visceral adipose function" and insulin sensitivity, and its increase is strongly associated with cardiometabolic risk.
945 citations
TL;DR: The data suggest that only a small number of neurophysiological tests are actually required to clinically differentiate individuals with neuropathy from those without, and variations in the population will need to be considered in future studies of diabetic neuropathy.
Abstract: Objective: To determine the relationships among large, small and autonomic fiber neurophysiologic measures in a cross sectional study of patients with diabetes. Research design and methods: We assessed 130 individuals: 25 healthy subjects and 105 subjects with diabetes. Subjects were classified by presence or absence of neuropathy by physical examination. All subjects underwent autonomic testing, nerve conduction studies, quantitative sensory testing and nerve-axon reflex vasodilation in addition to quantifiable neurologic examination and symptom scores. Correlation and cluster analysis were used to determine relationships between and among different neurophysiologic testing parameters. Results: Neurophysiologic tests were abnormal in patients with clinical evidence of diabetic neuropathy compared to healthy controls and those without neuropathy (P 0.9, P=NS to 0.5, P=NS to Conclusions: The modest correlation coefficients seen between the different testing modalities suggest these techniques measure different neurophysiologic parameters, and are therefore not interchangeable. However, the data suggest that only a small number of neurophysiologic tests are actually required to clinically differentiate individuals with neuropathy from those without. The natural clustering of both patients and healthy controls suggests that variations in the population will need to be considered in future studies of diabetic neuropathy.
888 citations
TL;DR: Ranibizumab is effective in improving BCVA and is well tolerated in DME, and future clinical trials are required to confirm its long-term efficacy and safety.
Abstract: OBJECTIVE The expression of vascular endothelial growth factor (VEGF) is elevated in diabetic macular edema (DME). Ranibizumab binds to and inhibits multiple VEGF variants. We investigated the safety and efficacy of ranibizumab in DME involving the foveal center. RESEARCH DESIGN AND METHODS This was a 12-month, multicenter, sham-controlled, double-masked study with eyes (age >18 years, type 1 or 2 diabetes, central retinal thickness [CRT] ≥300 μm, and best corrected visual acuity [BCVA] of 73–39 ETDRS letters [Early Treatment Diabetic Retinopathy Study]) randomly assigned to intravitreal ranibizumab (0.3 or 0.5 mg; n = 51 each) or sham ( n = 49). The treatment schedule comprised three monthly injections, after which treatment could be stopped/reinitiated with an opportunity for rescue laser photocoagulation (protocol-defined criteria). After month 1, dose-doubling was permitted (protocol-defined criteria, injection volume increased from 0.05 to 0.1 ml and remained at 0.1 ml thereafter). Efficacy (BCVA and CRT) and safety were compared between pooled ranibizumab and sham arms using the full analysis set ( n = 151, patients receiving ≥1 injection). RESULTS At month 12, mean ± SD BCVA improved from baseline by 10.3 ± 9.1 letters with ranibizumab and declined by 1.4 ± 14.2 letters with sham ( P P P CONCLUSIONS Ranibizumab is effective in improving BCVA and is well tolerated in DME. Future clinical trials are required to confirm its long-term efficacy and safety.
TL;DR: Although A1C detects much lower prevalences than glucose criteria, hyperglycemic conditions remain high in the U.S., and elderly and minority groups are disproportionately affected.
Abstract: OBJECTIVE We examined prevalences of previously diagnosed diabetes and undiagnosed diabetes and high risk for diabetes using recently suggested A1C criteria in the U.S. during 2003–2006. We compared these prevalences to those in earlier surveys and those using glucose criteria. RESEARCH DESIGN AND METHODS In 2003–2006, the National Health and Nutrition Examination Survey included a probability sample of 14,611 individuals aged ≥12 years. Participants were classified on glycemic status by interview for diagnosed diabetes and by A1C, fasting, and 2-h glucose challenge values measured in subsamples. RESULTS Using A1C criteria, the crude prevalence of total diabetes in adults aged ≥20 years was 9.6% (20.4 million), of which 19.0% was undiagnosed (7.8% diagnosed, 1.8% undiagnosed using A1C ≥6.5%). Another 3.5% of adults (7.4 million) were at high risk for diabetes (A1C 6.0 to P P CONCLUSIONS Although A1C detects much lower prevalences than glucose criteria, hyperglycemic conditions remain high in the U.S., and elderly and minority groups are disproportionately affected.
TL;DR: The near absence of hypoglycemia and an insulin-independent mechanism of action make dapagliflozin a unique addition to existing treatment options for type 2 diabetes.
Abstract: Objective – Dapagliflozin, a highly selective inhibitor of the renal sodium glucose co-transporter-2 (SGLT2), increases urinary excretion of glucose and lowers plasma glucose levels in an insulin-independent manner. We evaluated the efficacy and safety of dapagliflozin in treatment-naive patients with type 2 diabetes.
Research Design and Methods – This was a 24-week parallel-group, double-blind, placebo-controlled phase 3 trial. Patients with glycosylated hemoglobin (A1C) 7.0–10% (n=485) were randomly assigned to one of 7 arms to receive once-daily placebo or dapagliflozin 2.5, 5 or 10 mg once-daily in the morning (main cohort) or evening (exploratory cohort). Patients with A1C 10.1–12% (high-A1C exploratory cohort; n=73) were randomly assigned 1:1 to receive blinded treatment with a morning dose of dapagliflozin 5 or 10 mg/day. Primary endpoint was change from baseline in A1C in the main cohort, statistically tested using an analysis of covariance.
Results – In the main cohort, mean A1C changes from baseline at week 24 were −0.23% with placebo and −0.58%, −0.77% ( P =0.0005 vs placebo), and −0.89% ( P <0.0001 vs placebo) with dapagliflozin 2.5, 5, and 10 mg, respectively. Signs, symptoms and other reports suggestive of urinary tract infections and genital infection were more frequently noted in the dapagliflozin arms. There were no major episodes of hypoglycemia. Data from exploratory cohorts were consistent with these results.
Conclusions – Dapagliflozin lowered hyperglycemia in treatment-naive patients with newly diagnosed type 2 diabetes. The near absence of hypoglycemia and an insulin-independent mechanism of action make dapagliflozin a unique addition to existing treatment options for type 2 diabetes.
TL;DR: Following encouraging results in animals, several short-term randomized controlled trials showed the benefit of prebiotics and probiotics on insulin sensitivity, inflammatory markers, postprandial incretins, and glucose tolerance.
Abstract: The connection between gut microbiota and energy homeostasis and inflammation and its role in the pathogenesis of obesity-related disorders are increasingly recognized. Animals models of obesity connect an altered microbiota composition to the development of obesity, insulin resistance, and diabetes in the host through several mechanisms: increased energy harvest from the diet, altered fatty acid metabolism and composition in adipose tissue and liver, modulation of gut peptide YY and glucagon-like peptide (GLP)-1 secretion, activation of the lipopolysaccharide toll-like receptor-4 axis, and modulation of intestinal barrier integrity by GLP-2. Instrumental for gut microbiota manipulation is the understanding of mechanisms regulating gut microbiota composition. Several factors shape the gut microflora during infancy: mode of delivery, type of infant feeding, hospitalization, and prematurity. Furthermore, the key importance of antibiotic use and dietary nutrient composition are increasingly recognized. The role of the Western diet in promoting an obesogenic gut microbiota is being confirmation in subjects. Following encouraging results in animals, several short-term randomized controlled trials showed the benefit of prebiotics and probiotics on insulin sensitivity, inflammatory markers, postprandial incretins, and glucose tolerance. Future research is needed to unravel the hormonal, immunomodulatory, and metabolic mechanisms underlying microbe-microbe and microbiota-host interactions and the specific genes that determine the health benefit derived from probiotics. While awaiting further randomized trials assessing long-term safety and benefits on clinical end points, a healthy lifestyle—including breast lactation, appropriate antibiotic use, and the avoidance of excessive dietary fat intake—may ensure a friendly gut microbiota and positively affect prevention and treatment of metabolic disorders.
TL;DR: It is found that what has been called “depression” among type 2 diabetic patients may really be two conditions, MDD and diabetes distress, with only the latter displaying significant associations with A1C.
Abstract: OBJECTIVE To determine the concurrent, prospective, and time-concordant relationships among major depressive disorder (MDD), depressive symptoms, and diabetes distress with glycemic control. RESEARCH DESIGN AND METHODS In a noninterventional study, we assessed 506 type 2 diabetic patients for MDD (Composite International Diagnostic Interview), for depressive symptoms (Center for Epidemiological Studies-Depression), and for diabetes distress (Diabetes Distress Scale), along with self-management, stress, demographics, and diabetes status, at baseline and 9 and 18 months later. Using multilevel modeling (MLM), we explored the cross-sectional relationships of the three affective variables with A1C, the prospective relationships of baseline variables with change in A1C over time, and the time-concordant relationships with A1C. RESULTS All three affective variables were moderately intercorrelated, although the relationship between depressive symptoms and diabetes distress was greater than the relationship of either with MDD. In the cross-sectional MLM, only diabetes distress but not MDD or depressive symptoms was significantly associated with A1C. None of the three affective variables were linked with A1C in prospective analyses. Only diabetes distress displayed significant time-concordant relationships with A1C. CONCLUSIONS We found no concurrent or longitudinal association between MDD or depressive symptoms with A1C, whereas both concurrent and time-concordant relationships were found between diabetes distress and A1C. What has been called “depression” among type 2 diabetic patients may really be two conditions, MDD and diabetes distress, with only the latter displaying significant associations with A1C. Ongoing evaluation of both diabetes distress and MDD may be helpful in clinical settings.
TL;DR: Perioperative hyperglycemia is associated with increased LOS, hospital complications, and mortality after noncardiac general surgery, and Randomized controlled trials are needed to determine whether perioperative diabetes management improves clinical outcome in non Cardiac surgery patients.
Abstract: Background. Hospital hyperglycemia, in patients with and without diabetes has been identified as a marker of poor clinical outcome in cardiac surgery patients. It is not known; however, what is the impact of perioperative hyperglycemia on clinical outcome in general and noncardiac surgical patients. Methods. This observational study aimed to determine the relationship between pre- and post-surgery blood glucose levels and hospital length of stay (LOS), complications and mortality in 3,184 noncardiac surgical patients consecutively admitted to Emory University Hospital, Atlanta, GA between 1/1/07 and 6/30/07. Results. The overall 30-day mortality was 2.3%, with nonsurvivors having significantly higher blood glucose levels prior to and after surgery (both, p Conclusion. Perioperative hyperglycemia is associated with increased length of stay, hospital complications and mortality after noncardiac general surgery. Randomized controlled trials are needed to determine if perioperative diabetes management improves clinical outcome in noncardiac surgical patients.
TL;DR: Clinical care guidelines for cystic fibrosis–related diabetes are intended for use by CF patients, their care partners, and health care professionals and include recommendations for screening, diagnosis, and medical management of CFRD.
Abstract: Cystic fibrosis–related diabetes (CFRD) is the most common comorbidity in people with cystic fibrosis (CF), occurring in ∼20% of adolescents and 40–50% of adults (1). While it shares features of type 1 and type 2 diabetes, CFRD is a distinct clinical entity. It is primarily caused by insulin insufficiency, although fluctuating levels of insulin resistance related to acute and chronic illness also play a role. The additional diagnosis of CFRD has a negative impact on pulmonary function and survival in CF, and this risk disproportionately affects women (2–4). In contrast to patients with other types of diabetes, there are no documented cases of death from atherosclerotic vascular disease in patients with CFRD, despite the fact that some now live into their sixth and seventh decades.
These guidelines are the result of a joint effort between the Cystic Fibrosis Foundation (CFF), the American Diabetes Association (ADA), and the Pediatric Endocrine Society (PES). They are intended for use by CF patients, their care partners, and health care professionals and include recommendations for screening, diagnosis, and medical management of CFRD. This report focuses on aspects of care unique to CFRD. A comprehensive summary of recommendations for all people with diabetes can be found in the ADA Standards of Medical Care, published annually in the January supplement to Diabetes Care (5).
In 2009, CFF in collaboration with ADA and PES convened a committee of CF and diabetes experts to update clinical care guidelines for CFRD. Investigators at Johns Hopkins University conducted evidence reviews on relevant clinical questions identified by the guidelines committee. The reviews were provided to the committee to use in developing recommendations. Where possible, the evidence for each recommendation was considered and graded by the committee using the ADA (5) and the U.S. Preventive Services Task Force (USPSTF) (6 …
TL;DR: It is now well established that participation in regular PA improves blood glucose control and can prevent or delay type 2 diabetes, along with positively impacting lipids, blood pressure, cardiovascular events, mortality, and quality of life.
Abstract: Although physical activity (PA) is a key element in the prevention and management of type 2 diabetes, many with this chronic disease do not become or remain regularly active. High-quality studies establishing the importance of exercise and fitness in diabetes were lacking until recently, but it is now well established that participation in regular PA improves blood glucose control and can prevent or delay type 2 diabetes, along with positively impacting lipids, blood pressure, cardiovascular events, mortality, and quality of life. Structured interventions combining PA and modest weight loss have been shown to lower risk of type 2 diabetes by up to 58% in high-risk populations. Most benefits of PA on diabetes management are realized through acute and chronic improvements in insulin action, accomplished with both aerobic and resistance training. …
TL;DR: It is made the novel observation that TLR2 and TLR4 expression and their ligands, signaling, and functional activation are increased in recently diagnosed type 2 diabetes and contribute to the proinflammatory state.
Abstract: OBJECTIVE Individuals with type 2 diabetes have a myriad of metabolic aberrations including increased inflammation, increasing their cardiovascular risk. Toll-like receptors (TLRs) and their ligands play a key role in insulin resistance and atherosclerosis. However, there is a paucity of data examining the expression and activity of TLRs in type 2 diabetes. Thus, in the present study, we examined TLR2 and TLR4 mRNA and protein expression, their ligands, and signaling in monocytes of recently diagnosed type 2 diabetic patients.
RESEARCH DESIGN AND METHODS TLR mRNA, protein expression, TLR ligands, and TLR signaling were measured in freshly isolated monocytes from healthy human control subjects ( n = 23) and type 2 diabetic subjects ( n = 23) using real-time RT-PCR, Western blot, and flow cytometric assays.
RESULTS Type 2 diabetic subjects had significantly increased TLR2, TLR4 mRNA, and protein in monocytes compared with control subjects ( P < 0.05). Increased TLR2 and TLR4 expression correlated with BMI, homeostasis model assessment–insulin resistance (HOMA-IR), glucose, A1C, Ne-(carboxymethyl) lysine (CML), and free fatty acid (FFA). Ligands of TLR2 and TLR4, namely, HSP60, HSP70, HMGB1, endotoxin, and hyaluronan levels, were elevated in type 2 diabetic subjects and positively correlated with TLR2 and TLR4. Type 2 diabetic subjects showed increased MyD88, phosphorylated IRAK-1, Trif, TICAM-1, IRF-3, and NF-κB p65 expression in monocytes compared with control subjects. Furthermore, TLR-MyD88-NF-κB signaling resulted in elevated levels of cytokines ( P < 0.05), but increased interleukin (IL)-1β, interferon (IFN)-γ, and endotoxin were not significant when adjusted for BMI.
CONCLUSIONS In this comprehensive study, we make the novel observation that TLR2 and TLR4 expression and their ligands, signaling, and functional activation are increased in recently diagnosed type 2 diabetes and contribute to the proinflammatory state.
TL;DR: SO defined by ASM/Wt was more closely associated with metabolic syndrome than either sarcopenia or obesity alone, and the homeostasis model assessment of insulin resistance of subjects with SO was higher and they were at higher risk for metabolic syndrome.
Abstract: OBJECTIVE We investigated the prevalence of sarcopenic obesity (SO) and its relationship with metabolic syndrome in a community-based elderly cohort in Korea. RESEARCH DESIGN AND METHODS In this study, 287 men and 278 women aged 65 or older were recruited. Sarcopenia was defined as the appendicular skeletal muscle mass (ASM) divided by height squared (Ht 2 ) (kg/m 2 ) or by weight (Wt) (%) of 2 . RESULTS The prevalence of SO was 16.7% in men and 5.7% in women with sarcopenia defined by ASM/Ht 2 ; however, it was 35.1% in men and 48.1% in women by ASM/Wt. Using ASM/Wt, the homeostasis model assessment of insulin resistance of subjects with SO was higher and they were at higher risk for metabolic syndrome (odds ratio [OR] 8.28 [95% CI 4.45–15.40]) than the obese (5.51 [2.81–10.80]) or sarcopenic group (2.64 [1.08–6.44]). CONCLUSIONS SO defined by ASM/Wt was more closely associated with metabolic syndrome than either sarcopenia or obesity alone.
TL;DR: Clinical outcomes are the best way to define diagnostic thresholds, and this approach to GDM diagnosis has already been reported in the Brazilian population.
Abstract: Lack of international uniformity for the diagnosis of gestational diabetes mellitus (GDM) has been a clinical problem The International Association of Diabetes and Pregnancy Study Groups (IADPSG) suggested new criteria for diagnosis and classification of diabetes in pregnancy (1) based on the association of maternal glycemia with perinatal outcomes reported in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study (2)
Clinical outcomes are the best way to define diagnostic thresholds, and this approach to GDM diagnosis has already been reported in the Brazilian population The study by Schmidt et al (3) merits mentioning since it is one of the few large studies of unselected pregnant women universally evaluated with the …
TL;DR: The present meta-analysis suggests that periodontal treatment leads to an improvement of glycemic control in type 2 diabetic patients for at least 3 months.
Abstract: OBJECTIVE There is growing evidence that periodontitis may affect general health. This study was assigned to explore the robustness of observations that periodontal therapy leads to the improvement of glycemic control in diabetic patients. RESEARCH DESIGN AND METHODS A literature search (until March 2009) was carried out using two databases (MEDLINE and the Cochrane Library) with language restriction to English. Selection of publications was based on 1 ) original investigations, 2 ) controlled periodontal intervention studies where the diabetic control group received no periodontal treatment, and 3 ) study duration of ≥3 months. RESULTS Screening of the initial 639 identified studies and reference checking resulted in five suitable articles. A total of 371 patients were included in this analysis with periodontitis as predictor and the actual absolute change in A1C (ΔA1C) as the outcome. The duration of follow-up was 3–9 months. All studies described a research population of type 2 diabetic patients in whom glycemic control improved after periodontal therapy compared with the control group (range ΔA1C: Δ−1.17 up to Δ−0.05%). The studies in a meta-analysis demonstrated a weighted mean difference of ΔA1C before and after therapy of −0.40% (95% CI −0.77 to −0.04%, P = 0.03) favoring periodontal intervention in type 2 diabetic patients. Nevertheless, this improvement in %A1C must be interpreted with care due to limited robustness as evidenced by heterogeneity among studies (59.5%, P = 0.04). CONCLUSIONS The present meta-analysis suggests that periodontal treatment leads to an improvement of glycemic control in type 2 diabetic patients for at least 3 months.
TL;DR: In this study, 1,353 patients with type 2 diabetes enrolled in the Zwolle Outpatient Diabetes project Integrating Available Care study in the Netherlands were enrolled in a prospectively followed cohort, and metformin use was associated with lower cancer mortality compared with nonuse of met formin.
Abstract: OBJECTIVE Several studies have suggested an association between specific diabetes treatment and cancer mortality. We studied the association between metformin use and cancer mortality in a prospectively followed cohort. RESEARCH DESIGN AND METHODS In 1998 and 1999, 1,353 patients with type 2 diabetes were enrolled in the Zwolle Outpatient Diabetes project Integrating Available Care (ZODIAC) study in the Netherlands. Vital status was assessed in January 2009. Cancer mortality rate was evaluated using standardized mortality ratios (SMRs), and the association between metformin use and cancer mortality was evaluated with a Cox proportional hazards model, taking possible confounders into account. RESULTS Median follow-up time was 9.6 years, average age at baseline was 68 years, and average A1C was 7.5%. Of the patients, 570 died, of which 122 died of malignancies. The SMR for cancer mortality was 1.47 (95% CI 1.22–1.76). In patients taking metformin compared with patients not taking metformin at baseline, the adjusted hazard ratio (HR) for cancer mortality was 0.43 (95% CI 0.23–0.80), and the HR with every increase of 1 g of metformin was 0.58 (95% CI 0.36–0.93). CONCLUSIONS In general, patients with type 2 diabetes are at increased risk for cancer mortality. In our group, metformin use was associated with lower cancer mortality compared with nonuse of metformin. Although the design cannot provide a conclusion about causality, our results suggest a protective effect of metformin on cancer mortality.
TL;DR: Type 2 diabetes was associated with increased risk of sarcopenia and body compositional parameters may contribute to physical disability and metabolic disorders in older adults with diabetes.
Abstract: OBJECTIVE We examined prevalence of sarcopenia in Korean patients with type 2 diabetes and compared body compositional parameters between subjects with and without type 2 diabetes.
RESEARCH DESIGN AND METHODS The Korean Sarcopenic Obesity Study (KSOS) included 810 subjects (414 patients with diabetes and 396 control subjects) who were examined using dual-energy X-ray absorptiometry. Prevalence of sarcopenia was defined using the skeletal muscle index (SMI).
RESULTS Prevalence in patients with diabetes and in the control group was 15.7 and 6.9%, respectively. In both men and women, SMI values were significantly decreased in patients with diabetes compared with subjects without diabetes. Furthermore, multiple logistic regression analysis showed that type 2 diabetes was independently associated with sarcopenia.
CONCLUSIONS Type 2 diabetes was associated with increased risk of sarcopenia. These characteristics may contribute to physical disability and metabolic disorders in older adults with diabetes.
TL;DR: Among people with type 2 diabetes, major depression is associated with an increased risk of clinically significant microvascular and macrovascular complications over the ensuing 5 years, even after adjusting for diabetes severity and self-care activities.
Abstract: OBJECTIVE To prospectively examine the association of depression with risks for advanced macrovascular and microvascular complications among patients with type 2 diabetes. RESEARCH DESIGN AND METHODS A longitudinal cohort of 4,623 primary care patients with type 2 diabetes was enrolled in 2000–2002 and followed through 2005–2007. Advanced microvascular complications included blindness, end-stage renal disease, amputations, and renal failure deaths. Advanced macrovascular complications included myocardial infarction, stroke, cardiovascular procedures, and deaths. Medical record review, ICD-9 diagnostic and procedural codes, and death certificate data were used to ascertain outcomes in the 5-year follow-up. Proportional hazard models analyzed the association between baseline depression and risks of adverse outcomes. RESULTS After adjustment for prior complications and demographic, clinical, and diabetes self-care variables, major depression was associated with significantly higher risks of adverse microvascular outcomes (hazard ratio 1.36 [95% CI 1.05–1.75]) and adverse macrovascular outcomes (1.24 [1.0–1.54]). CONCLUSIONS Among people with type 2 diabetes, major depression is associated with an increased risk of clinically significant microvascular and macrovascular complications over the ensuing 5 years, even after adjusting for diabetes severity and self-care activities. Clinical and public health significance of these findings rises as the incidence of type 2 diabetes soars. Further research is needed to clarify the underlying mechanisms for this association and to test interventions to reduce the risk of diabetes complications among patients with comorbid depression.
TL;DR: A decreased risk of breast cancer was observed in female patients with type 2 diabetes using metformin on a long-term basis, and neither short-term met formin use nor use of sulfonylureas or other antidiabetes drugs was associated with a materially altered risk for breast cancer.
Abstract: OBJECTIVE To evaluate whether use of oral hypoglycemic agents is associated with an altered breast cancer risk in women. RESEARCH DESIGN AND METHODS Using the U.K.-based General Practice Research Database, we conducted a nested case-control analysis among 22,621 female users of oral antidiabetes drugs with type 2 diabetes. We evaluated whether they had an altered risk of breast cancer in relation to use of various types of oral hypoglycemic agents. Case and control patients with a recorded diagnosis of type 2 diabetes were matched on age, calendar time, and general practice, and the multivariate conditional logistic regression analyses were further adjusted for use of oral antidiabetes drugs, insulin, estrogens, smoking BMI, diabetes duration, and HbA1c (A1C). RESULTS We identified 305 case patients with a recorded incident diagnosis of breast cancer. The mean ± SD age was 67.5 ± 10.5 years at the time of the cancer diagnosis. Long-term use of ≥40 prescriptions (>5 years) of metformin, based on 17 exposed case patients and 120 exposed control patients, was associated with an adjusted odds ratio of 0.44 (95% CI 0.24–0.82) for developing breast cancer compared with no use of metformin. Neither short-term metformin use nor use of sulfonylureas or other antidiabetes drugs was associated with a materially altered risk for breast cancer. CONCLUSIONS A decreased risk of breast cancer was observed in female patients with type 2 diabetes using metformin on a long-term basis.
TL;DR: A systematic review of literature on the CE of diabetes interventions recommended by the American Diabetes Association found strong evidence to classify the following interventions as cost saving or very cost-effective.
Abstract: OBJECTIVE To synthesize the cost-effectiveness (CE) of interventions to prevent and control diabetes, its complications, and comorbidities. RESEARCH DESIGN AND METHODS We conducted a systematic review of literature on the CE of diabetes interventions recommended by the American Diabetes Association (ADA) and published between January 1985 and May 2008. We categorized the strength of evidence about the CE of an intervention as strong, supportive, or uncertain. CEs were classified as cost saving (more health benefit at a lower cost), very cost-effective (≤$25,000 per life year gained [LYG] or quality-adjusted life year [QALY]), cost-effective ($25,001 to $50,000 per LYG or QALY), marginally cost-effective ($50,001 to $100,000 per LYG or QALY), or not cost-effective (>$100,000 per LYG or QALY). The CE classification of an intervention was reported separately by country setting (U.S. or other developed countries) if CE varied by where the intervention was implemented. Costs were measured in 2007 U.S. dollars. RESULTS Fifty-six studies from 20 countries met the inclusion criteria. A large majority of the ADA recommended interventions are cost-effective. We found strong evidence to classify the following interventions as cost saving or very cost-effective: (I) Cost saving— 1 ) ACE inhibitor (ACEI) therapy for intensive hypertension control compared with standard hypertension control; 2 ) ACEI or angiotensin receptor blocker (ARB) therapy to prevent end-stage renal disease (ESRD) compared with no ACEI or ARB treatment; 3 ) early irbesartan therapy (at the microalbuminuria stage) to prevent ESRD compared with later treatment (at the macroalbuminuria stage); 4 ) comprehensive foot care to prevent ulcers compared with usual care; 5 ) multi-component interventions for diabetic risk factor control and early detection of complications compared with conventional insulin therapy for persons with type 1 diabetes; and 6 ) multi-component interventions for diabetic risk factor control and early detection of complications compared with standard glycemic control for persons with type 2 diabetes. (II) Very cost-effective— 1 ) intensive lifestyle interventions to prevent type 2 diabetes among persons with impaired glucose tolerance compared with standard lifestyle recommendations; 2 ) universal opportunistic screening for undiagnosed type 2 diabetes in African Americans between 45 and 54 years old; 3 ) intensive glycemic control as implemented in the UK Prospective Diabetes Study in persons with newly diagnosed type 2 diabetes compared with conventional glycemic control; 4 ) statin therapy for secondary prevention of cardiovascular disease compared with no statin therapy; 5 ) counseling and treatment for smoking cessation compared with no counseling and treatment; 6 ) annual screening for diabetic retinopathy and ensuing treatment in persons with type 1 diabetes compared with no screening; 7 ) annual screening for diabetic retinopathy and ensuing treatment in persons with type 2 diabetes compared with no screening; and 8 ) immediate vitrectomy to treat diabetic retinopathy compared with deferred vitrectomy. CONCLUSIONS Many interventions intended to prevent/control diabetes are cost saving or very cost-effective and supported by strong evidence. Policy makers should consider giving these interventions a higher priority.
TL;DR: These analyses implicate factors associated with persisting higher A1C levels, rather than low A 1C per se, as likely contributors to the increased mortality risk associated with the intensive glycemic treatment strategy in ACCORD.
Abstract: OBJECTIVE Randomized treatment comparing an intensive glycemic treatment strategy with a standard strategy in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial was ended early because of an unexpected excess of mortality in the intensive arm. As part of ongoing post hoc analyses of potential mechanisms for this finding, we explored whether on-treatment A1C itself had an independent relationship with mortality. RESEARCH DESIGN AND METHODS Participants with type 2 diabetes ( n = 10,251 with mean age 62 years, median duration of diabetes 10 years, and median A1C 8.1%) were randomly assigned to treatment strategies targeting either A1C RESULTS Various characteristics of the participants and the study sites at baseline had significant associations with the risk of mortality. Before and after adjustment for these covariates, a higher average on-treatment A1C was a stronger predictor of mortality than the A1C for the last interval of follow-up or the decrease of A1C in the first year. Higher average A1C was associated with greater risk of death. The risk of death with the intensive strategy increased approximately linearly from 6–9% A1C and appeared to be greater with the intensive than with the standard strategy only when average A1C was >7%. CONCLUSIONS These analyses implicate factors associated with persisting higher A1C levels, rather than low A1C per se, as likely contributors to the increased mortality risk associated with the intensive glycemic treatment strategy in ACCORD.
TL;DR: Whereas CAN was associated with increased mortality in this high-risk type 2 diabetes cohort, these analyses indicate that participants with CAN at baseline had similar mortality outcomes from intensive compared with standard glycemia treatment in the ACCORD cohort.
Abstract: OBJECTIVE Intensive therapy targeting normal blood glucose increased mortality compared with standard treatment in a randomized clinical trial of 10,251 participants with type 2 diabetes at high-risk for cardiovascular disease (CVD) events. We evaluated whether the presence of cardiac autonomic neuropathy (CAN) at baseline modified the effect of intensive compared with standard glycemia treatment on mortality outcomes in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial participants.
RESEARCH DESIGN AND METHODS CAN was assessed by measures of heart rate variability (HRV) and QT index (QTI) computed from 10-s resting electrocardiograms in 8,135 ACCORD trial participants with valid measurements (mean age 63.0 years, 40% women). Prespecified CAN definitions included a composite of the lowest quartile of HRV and highest QTI quartile in the presence or absence of peripheral neuropathy. Outcomes were all-cause and CVD mortality. Associations between CAN and mortality were evaluated by proportional hazards analysis, adjusting for treatment group allocation, CVD history, and multiple prespecified baseline covariates.
RESULTS During a mean 3.5 years follow-up, there were 329 deaths from all causes. In fully adjusted analyses, participants with baseline CAN were 1.55–2.14 times as likely to die as participants without CAN, depending on the CAN definition used ( P 0.7).
CONCLUSIONS Whereas CAN was associated with increased mortality in this high-risk type 2 diabetes cohort, these analyses indicate that participants with CAN at baseline had similar mortality outcomes from intensive compared with standard glycemia treatment in the ACCORD cohort.
TL;DR: A review of this topic is both timely and important for physicians to better understand how to assess the complexity of conditions present in patients with diabetes in order to establish safe treatment targets.
Abstract: This review covers the epidemiology, pathophysiology, clinical presentation, and diagnosis of cardiac autonomic neuropathy (CAN) in diabetes and discusses current evidence on approaches to prevention and treatment of CAN.
A 26-year-old woman with “brittle” type 1 diabetes and severe CAN experienced sudden cardiac death. She had a 16-year history of poor diabetes control presenting with wide blood glucose fluctuations, recurrent episodes of severe hypoglycemia, and hypoglycemia unawareness. Over time she developed persistent orthostatic hypotension with daily falls in systolic blood pressure ranging from 30–60 mmHg. These episodes had significant impact on her daily activities and required intermittent therapy with the α-1 agonist midodrine. Other complications included severe gastroparesis, refractory diarrhea, and painful diabetic peripheral neuropathy. Her last clinical examination revealed resting tachycardia with a fixed rate of 115 bpm, supine blood pressure of 110/78 mmHg, which dropped to 70/48 mmHg while standing, symmetrical absent pinprick and temperature discrimination in stocking distribution, and left Charcot joint. Her last pertinent laboratory findings were A1C 8.7%, creatinine 1.9 mg/dl, microalbumin/creatinine 496 mg/g, and hemoglobin 10.8 g/dl.
CAN represents a significant cause of morbidity and mortality in diabetic patients and is associated with a high risk of cardiac arrhythmias and sudden death, possibly related to silent myocardial ischemia. Therefore, it has important clinical and prognostic relevance. Recent reports of major clinical trials undermine established thinking concerning glycemic control and cardiac risk. Thus, a review of this topic is both timely and important for physicians to better understand how to assess the complexity of conditions present in patients with diabetes in order to establish safe treatment targets.
Diabetes affects more than 23 million people in the U.S. (www.diabetes.org) and an estimated 250 million worldwide (www.who.int/diabetes). Diabetic neuropathies, including CAN, are a common chronic complication of type 1 and type 2 diabetes and confer high morbidity …