Aleksandra Zuk

Prevalence of Diagnosed and Undiagnosed Type 2 Diabetes Mellitus Among US Adolescents: Results From the Continuous NHANES, 1999–2010

Although prevalence and incidence of type 2 diabetes mellitus (T2DM) are reportedly increasing among adolescents, national data are lacking, particularly in regard to undiagnosed T2DM. To estimate the prevalence of diagnosed and undiagnosed T2DM among US adolescents, we analyzed a nationally representative cross-section of 11,888 adolescents aged 12-19 years who received a diabetes interview in the Continuous National Health and Nutrition Examination Survey during 1999-2010. Among them, a random subsample of 4,661 adolescents also had fasting blood samples collected. Persons who reported a previous diabetes diagnosis and were either taking no medication or taking an oral hypoglycemic agent (with or without insulin) were classified as having T2DM; persons who reported using insulin alone were classified as having type 1 diabetes. Undiagnosed diabetes was defined as a fasting plasma glucose concentration of ≥126 mg/dL and was assumed to be type 2. In the fasting subsample, 31 diabetes cases (types 1 and 2) were identified, representing a prevalence of 0.84% (weighted 95% confidence interval (CI): 0.51, 1.40) (276,638 cases; 95% CI: 134,255, 419,020). Estimates of the prevalences of type 1 and type 2 diabetes were 0.48% (95% CI: 0.23, 1.02) and 0.36% (95% CI: 0.20, 0.67), respectively, indicating that T2DM accounted for 43% of all cases. Further, undiagnosed T2DM prevalence was 0.12% (95% CI: 0.05, 0.31), representing 34% of T2DM cases (40,611 cases; 95% CI: 2,850, 78,373). T2DM accounts for approximately half of adolescent diabetes in the United States, and one-third of these cases are undiagnosed.

The Influence of Anti-Infective Periodontal Treatment on C-Reactive Protein: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background Periodontal infections are hypothesized to increase the risk of adverse systemic outcomes through inflammatory mechanisms. The magnitude of effect, if any, of anti-infective periodontal treatment on systemic inflammation is unknown, as are the patient populations most likely to benefit. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to test the hypothesis that anti-infective periodontal treatment reduces systemic c-reactive protein (CRP). Methods and Findings MEDLINE, EMBASE, CENTRAL and CINAHL databases were searched using sensitivity-enhancing search terms. Eligible RCTs enrolled patients with periodontal infection, compared a clearly defined anti-infective periodontal intervention (experimental group) to an “inactive control” (no periodontal intervention) or to an “active control” (lower treatment intensity than the experimental group). Mean differences in final CRP values at the earliest post-treatment time point (typically 1-3 months) between experimental and control groups were analyzed using random-effects regression. Among 2,753 possible studies 20 were selected, which included 2,561 randomized patients(median=57). Baseline CRP values were >3.0 mg/L in 40% of trials. Among studies with a control group receiving no treatment, the mean difference in CRP final values among experimental treatment vs. control groups was -0.37 mg/L [95%CI=-0.64, -0.11], (P=0.005), favoring experimental treatment. Trials for which the experimental group received antibiotics had stronger effects (P for interaction=0.03) and the mean difference in CRP final values among experimental treatment vs. control was -0.75 mg/L [95%CI=-1.17,-0.33]. No treatment effect was observed among studies using an active treatment comparator. Treatment effects were stronger for studies that included patients with co-morbidities vs. studies that included “systemically healthy” patients, although the interaction was not significant (P=0.48). Conclusions Anti-infective periodontal treatment results in short-term modest reductions in systemic CRP.

Periodontal Bacteria and Prediabetes Prevalence in ORIGINS The Oral Infections, Glucose Intolerance, and Insulin Resistance Study

Periodontitis and type 2 diabetes mellitus are known to be associated. The relationship between periodontal microbiota and early diabetes risk has not been studied. We investigated the association between periodontal bacteria and prediabetes prevalence among diabetes-free adults. ORIGINS (the Oral Infections, Glucose Intolerance and Insulin Resistance Study) cross sectionally enrolled 300 diabetes-free adults aged 20 to 55 y (mean ± SD, 34 ± 10 y; 77% female). Prediabetes was defined as follows: 1) hemoglobin A1c values ranging from 5.7% to 6.4% or 2) fasting plasma glucose ranging from 100 to 125 mg/dL. In 1,188 subgingival plaque samples, 11 bacterial species were assessed at baseline, including Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia, and Actinomyces naeslundii. Full-mouth clinical periodontal examinations were performed, and participants were defined as having no/mild periodontitis vs. moderate/severe periodontitis per the definition of the Centers for Disease Control and Prevention / American Academy of Periodontology. Modified Poisson regression evaluated prediabetes prevalence across bacterial tertiles. Prevalence ratios and 95% confidence intervals for third vs. first tertiles are presented. All analyses were adjusted for cardiometabolic risk factors. All results presented currently arise from the baseline cross section. Prediabetes prevalence was 18%, and 58% of participants had moderate/severe periodontitis. Prevalence ratios (95% confidence intervals) summarizing associations between bacterial levels and prediabetes were as follows: A. actinomycetemcomitans, 2.48 (1.34, 4.58), P = 0.004; P. gingivalis, 3.41 (1.78, 6.58), P = 0.0003; T. denticola, 1.99 (0.992, 4.00), P = 0.052; T. forsythia, 1.95 (1.0, 3.84), P = 0.05; A. naeslundii, 0.46 (0.25, 0.85), P = 0.01. The prevalence ratio for prediabetes among participants with moderate/severe vs. no/mild periodontitis was 1.47 (0.78, 2.74), P = 0.23. Higher colonization levels of specific periodontal microbiota are associated with higher prediabetes prevalence among diabetes-free adults.

Prevalence of Prediabetes and Undiagnosed Diabetes in Canada (2007–2011) According to Fasting Plasma Glucose and HbA1c Screening Criteria

OBJECTIVE To provide the first population-based estimates of prediabetes and undiagnosed type 2 diabetes prevalence in Canada. RESEARCH DESIGN AND METHODS We combined two fasting subsamples of the Canadian Health Measures Survey, which were restricted to nonpregnant adults ≥20 years of age (N = 3,494). Undiagnosed diabetes was defined as not having self-reported type 2 diabetes but having blood glucose measures that met Canadian guidelines (i.e., fasting plasma glucose [FPG] level of ≥7.0 mmol/L or hemoglobin A1c [HbA1c] level of ≥6.5% [≥48 mmol/mol]). Prediabetes was defined as an FPG level of ≥6.1 and <7.0 mmol/L or an HbA1c level of ≥6.0% and <6.5% (≥42 and <48 mmol/mol). All estimates were weighted using survey sampling weights. CIs were calculated with the bootstrap method. RESULTS According to FPG levels, the prevalence of undiagnosed type 2 diabetes in Canadian adults was 1.13% (95% CI 0.79, 1.62), contributing to ∼20% of total type 2 diabetes prevalence (5.62 [95% CI 4.52, 6.95]). Compared with FPG levels, the undiagnosed prevalence was greater using HbA1c level as a criterion (3.09% [95% CI 1.97, 4.81]), ∼41% of the total number of cases of diabetes (7.55 [95% CI 5.98, 9.49]). The HbA1c-only criterion resulted in a threefold increase in prediabetes prevalence overall and a sixfold increase among females (FPG 2.22%, HbA1c 13.31%). Screening based on FPG only identified older undiagnosed case patients, with a mean age of 58.7 years (95% CI 59.9, 63.4). Similarly, using HbA1c identified younger individuals with prediabetes, with reduced BMI and waist circumference compared with FPG levels. CONCLUSIONS In this first study of a nationally representative sample with biospecimen measures, we found that the prevalence of undiagnosed type 2 diabetes and prediabetes was significantly higher using HbA1c levels compared with FPG levels. Further evaluation is needed to fully assess the impact of using the HbA1c criterion.

The Prevalence of Undiagnosed and Prediabetes Diabetes in Canada (2007–2011) According to Fasting Plasma Glucose and HbA1c Screening Criteria

OBJECTIVE To provide the first population-based estimates of prediabetes and undiagnosed type 2 diabetes prevalence in Canada. RESEARCH DESIGN AND METHODS We combined two fasting subsamples of the Canadian Health Measures Survey, which were restricted to nonpregnant adults ≥20 years of age (N = 3,494). Undiagnosed diabetes was defined as not having self-reported type 2 diabetes but having blood glucose measures that met Canadian guidelines (i.e., fasting plasma glucose [FPG] level of ≥7.0 mmol/L or hemoglobin A1c [HbA1c] level of ≥6.5% [≥48 mmol/mol]). Prediabetes was defined as an FPG level of ≥6.1 and <7.0 mmol/L or an HbA1c level of ≥6.0% and <6.5% (≥42 and <48 mmol/mol). All estimates were weighted using survey sampling weights. CIs were calculated with the bootstrap method. RESULTS According to FPG levels, the prevalence of undiagnosed type 2 diabetes in Canadian adults was 1.13% (95% CI 0.79, 1.62), contributing to ∼20% of total type 2 diabetes prevalence (5.62 [95% CI 4.52, 6.95]). Compared with FPG levels, the undiagnosed prevalence was greater using HbA1c level as a criterion (3.09% [95% CI 1.97, 4.81]), ∼41% of the total number of cases of diabetes (7.55 [95% CI 5.98, 9.49]). The HbA1c-only criterion resulted in a threefold increase in prediabetes prevalence overall and a sixfold increase among females (FPG 2.22%, HbA1c 13.31%). Screening based on FPG only identified older undiagnosed case patients, with a mean age of 58.7 years (95% CI 59.9, 63.4). Similarly, using HbA1c identified younger individuals with prediabetes, with reduced BMI and waist circumference compared with FPG levels. CONCLUSIONS In this first study of a nationally representative sample with biospecimen measures, we found that the prevalence of undiagnosed type 2 diabetes and prediabetes was significantly higher using HbA1c levels compared with FPG levels. Further evaluation is needed to fully assess the impact of using the HbA1c criterion.

Effect of Vitamin D3 Supplementation on Inflammatory Markers and Glycemic Measures among Overweight or Obese Adults: A Systematic Review of Randomized Controlled Trials.

Background Obesity induced low-grade chronic inflammation disrupts proper immune and metabolic function. Vitamin D deficiency increases inflammation, which is associated with cardiometabolic risk. This systematic review examines the association between oral vitamin D (VD) supplementation and circulating inflammatory biomarkers and glycemic outcomes from randomized controlled trials (RCTs) of overweight and/or obese adults. Methods MEDLINE OVID, EMBASE and the Cochrane Central Register of Controlled Trials were searched according to a predefined protocol. Eligible RCTs included adults randomized to receive either oral VD or placebo. Two reviewers independently assessed RCTs for inclusion. Bias was assessed using the Cochrane Collaboration risk of bias tool. Mean differences were calculated comparing end-of-study sample means between the independent VD and placebo groups. Results Eleven unique RCTs met inclusion criteria from a total of 3,383 identified citations, including 79 screened articles and 14 full text data extractions. Inflammatory and glycemic measures were reported in 7 and 10 RCTs, respectively. Most trial findings were non-significant with considerable heterogeneity in design, participants and outcomes. All but one trial was rated as either high or unclear risk of bias. Two RCTs reported significant changes in inflammatory biomarkers; however, the mean difference between groups was not statistically significant: C-reactive protein 0.19 mg/L (p = 0.88); Tumor Necrosis Factor -0.54 pg/ml (p = 0.20). Two other trials found significant mean differences in fasting plasma glucose -0.32 mmol/L (p = 0.03), Hemoglobin A1c -0.13% (p = 0.04), and Homeostatic Model Assessment -0.86 (p = 0.02) following VD supplementation. Conclusions Overall, there is no clear established benefit of VD supplementation on inflammatory biomarkers among overweight/obese adults. Baseline serum VD possibly influences the effect of VD repletion on inflammatory markers. Risk of bias was present in most studies, thus supporting the need for higher quality studies in this area to more conclusively understand the role VD supplementation has on inflammatory pathways.

Joint effects of serum vitamin D insufficiency and periodontitis on insulin resistance, pre-diabetes, and type 2 diabetes: results from the National Health and Nutrition Examination Survey (NHANES) 2009–2010

Objective Periodontitis is strongly associated with diabetes and is increasingly shown to be associated with other glycemic abnormalities. Vitamin D is postulated to have both anti-inflammatory and antimicrobial activity. Therefore, our aim was to investigate the joint effects of both serum 25-hydroxyvitamin D3 and total 25-hydroxyvitamin D with periodontitis on homeostatic model assessment for insulin resistance (HOMA-IR), pre-diabetes, and type 2 diabetes. Research design and methods Using data from the 2009–2010 National Health and Nutrition Examination Survey, the sample was restricted to adults over 30 years of age, who were eligible for oral health examination, and had vitamin D, fasting glucose and insulin measures. The analytic sample includes those with (n=1631) and without (n=1369) type 2 diabetes. Using survey logistic multivariable regression analysis, we examined the following joint effects: (1) vitamin D insufficiency (<50 nmol/L) and moderate to severe periodontitis (VD+PD+); (2) vitamin D insufficiency and mild to no periodontitis (VD+PD−); and (3) vitamin D sufficiency ) (>50 nmol/L) and periodontitis (VD−PD+), and compared these groups with the doubly unexposed reference group (VD−PD−). Results Consistently, the joint effects of vitamin D3 insufficiency and total vitamin D insufficiency with periodontitis (VD+PD+) were significantly associated with diabetes: OR=2.83 (95% CI 1.34 to 5.96) and OR=1.98 (95% CI 1.04 to 3.76), respectively. However, the joint effects of vitamin D3 insufficiency and periodontitis were attenuated for HOMA-IR 4.17: OR=1.57 (95% CI 0.97 to 2.55). Pre-diabetes was not associated with either joint effects. Conclusion In this cross-sectional, nationally representative sample, the joint effects of vitamin D and periodontitis appear to differ for HOMA-IR, pre-diabetes and diabetes.

Diabetes Prevalence Among Youth

Author Contributions: Dr Ford had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Ford, Maynard. Acquisition, analysis, or interpretation of data: All authors. Drafting of the manuscript: Ford. Critical revision of the manuscript for important intellectual content: All authors. Statistical analysis: Ford. Administrative, technical, or material support: Maynard. Study supervision: Ford.