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Nicotine Metabolism in Adults With Type 2 Diabetes.

ABSTRACT: INTRODUCTION:Metabolism of nicotine has implications for addiction and may be altered in people with type 2 diabetes. Thus, our objective was to analyze nicotine metabolism in adults with and without type 2 diabetes who smoke. METHODS:From an existing cross-sectional study, we analyzed nicotine metabolism in urine of 148 smokers, 36 type 2 diabetics (insulin or antidiabetic medication use and/or fasting glucose >126 mg/dL) and 112 non-diabetics. Nicotine metabolism was quantified as the nicotine metabolite ratio (NMR) = trans-3'-hydroxycotinine (3HC) divided by cotinine (COT). COT and 3HC were measured in the participant urine by ultra-performance liquid chromatography-tandem mass spectrometry. Generalized linear models were used to assess whether NMR was associated with diabetic status (yes/no). RESULTS:Participants categorized as high NMR smoked more cigarettes per day (p = .002) and were more likely to be diabetic (p = .022) compared to low NMR. We found no significant difference in total nicotine equivalents defined as the sum of the nicotine, COT, and 3HC (p > .05). In unadjusted models, NMR was 42.5% higher in diabetics versus non-diabetics (95% confidence interval [CI]: 12.9, 79.8; p = .003). In models adjusted for factors significantly different between low versus high NMR participants, mean NMR was 36.5% higher in the diabetics versus non-diabetics (95% CI: 7.8, 72.8; p = .010). Additionally, in models adjusted for known confounders of NMR, NMR was 40.6% higher in diabetics versus non-diabetics (95% CI: 9.9, 80.0; p = .007). CONCLUSIONS:From these data, we infer that type 2 diabetics metabolize nicotine faster, which may increase the potential for nicotine addiction. IMPLICATIONS:Smoking is addictive and this addiction may be related to tobacco metabolism. Individuals with faster metabolism of nicotine tend to smoke more cigarettes for longer periods of time. People with type 2 diabetes may metabolize nicotine faster, which could lead to higher lifetime tobacco burden, increasing the adverse health outcomes associated with increased exposure to tobacco.

SUBMITTER: Keith RJ

PROVIDER: S-EPMC6528156 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Nicotine Metabolism in Adults With Type 2 Diabetes.

Keith Rachel J RJ Riggs Daniel W DW Conklin Daniel J DJ Lorkiewicz Pawel P Srivastava Sanjay S Bhatnagar Aruni A DeFilippis Andrew P AP

Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco 20190501 6

<h4>Introduction</h4>Metabolism of nicotine has implications for addiction and may be altered in people with type 2 diabetes. Thus, our objective was to analyze nicotine metabolism in adults with and without type 2 diabetes who smoke.<h4>Methods</h4>From an existing cross-sectional study, we analyzed nicotine metabolism in urine of 148 smokers, 36 type 2 diabetics (insulin or antidiabetic medication use and/or fasting glucose >126 mg/dL) and 112 non-diabetics. Nicotine metabolism was quantified ...[more]

PMID: 29059414

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Project description:Aims/hypothesisSphingolipids play important roles in beta cell physiology, by regulating proinsulin folding and insulin secretion and in controlling apoptosis, as studied in animal models and cell cultures. Here we investigate whether sphingolipid metabolism may contribute to the pathogenesis of human type 1 diabetes and whether increasing the levels of the sphingolipid sulfatide would prevent models of diabetes in NOD mice.MethodsWe examined the amount and distribution of sulfatide in human pancreatic islets by immunohistochemistry, immunofluorescence and electron microscopy. Transcriptional analysis was used to evaluate expression of sphingolipid-related genes in isolated human islets. Genome-wide association studies (GWAS) and a T cell proliferation assay were used to identify type 1 diabetes related polymorphisms and test how these affect cellular islet autoimmunity. Finally, we treated NOD mice with fenofibrate, a known activator of sulfatide biosynthesis, to evaluate the effect on experimental autoimmune diabetes development.ResultsWe found reduced amounts of sulfatide, 23% of the levels in control participants, in pancreatic islets of individuals with newly diagnosed type 1 diabetes, which were associated with reduced expression of enzymes involved in sphingolipid metabolism. Next, we discovered eight gene polymorphisms (ORMDL3, SPHK2, B4GALNT1, SLC1A5, GALC, PPARD, PPARG and B4GALT1) involved in sphingolipid metabolism that contribute to the genetic predisposition to type 1 diabetes. These gene polymorphisms correlated with the degree of cellular islet autoimmunity in a cohort of individuals with type 1 diabetes. Finally, using fenofibrate, which activates sulfatide biosynthesis, we completely prevented diabetes in NOD mice and even reversed the disease in half of otherwise diabetic animals.Conclusions/interpretationThese results indicate that islet sphingolipid metabolism is abnormal in type 1 diabetes and suggest that modulation may represent a novel therapeutic approach.Data availabilityThe RNA expression data is available online at https://www.dropbox.com/s/93mk5tzl5fdyo6b/Abnormal%20islet%20sphingolipid%20metabolism%20in%20type%201%20diabetes%2C%20RNA%20expression.xlsx?dl=0 . A list of SNPs identified is available at https://www.dropbox.com/s/yfojma9xanpp2ju/Abnormal%20islet%20sphingolipid%20metabolism%20in%20type%201%20diabetes%20SNP.xlsx?dl=0 .

Project description:IntroductionClinician-led diabetes education is a fundamental component of care to assist people with Type 1 diabetes (T1D) self-manage their disease. Recent initiatives to incorporate a more patient-centered approach to diabetes education have included recommendations to make such education more individualized. Yet there is a dearth of research that identifies patients' perceptions of clinician-led diabetes education. We aimed to describe the experience of diabetes education from the perspective of young adults with T1D.MethodsWe designed a self-reported survey for Australian adults, aged 18-35 years, with T1D. Participants (n = 150) were recruited by advertisements through diabetes consumer-organizations. Respondents were asked to rate aspects of clinician-led diabetes education and identify sources of self-education. To expand on the results of the survey we interviewed 33 respondents in focus groups.ResultsSurveyThe majority of respondents (56.0%) were satisfied with the amount of continuing clinician-led diabetes education; 96.7% sought further self-education; 73.3% sourced more diabetes education themselves than that provided by their clinicians; 80.7% referred to diabetes organization websites for further education; and 30.0% used online chat-rooms and blogs for education. Focus groups: The three key themes that emerged from the interview data were deficiencies related to the pedagogy of diabetes education; knowledge deficiencies arising from the gap between theoretical diabetes education and practical reality; and the need for and problems associated with autonomous and peer-led diabetes education.ConclusionOur findings indicate that there are opportunities to improve clinician led-diabetes education to improve patient outcomes by enhancing autonomous health-literacy skills and to incorporate peer-led diabetes education and support with clinician-led education. The results provide evidence for the potential value of patient engagement in quality improvement and health-service redesign.

Project description:Preclinical models of type 1 diabetes mellitus exhibit marked declines in skeletal muscle health including significant impairments in muscle repair. The present study investigated, for the first time, whether muscle repair was altered in young adults with uncomplicated type 1 diabetes (T1D) following damaging exercise.In this cohort study, eighteen physically-active young adults (M=22.1, SEM=0.9 years) with T1D (n, male/female=4/5; MHbA1c= 58, SEMHbA1c=5.9 mmol/mol) and without T1D (n, male/female=4/5) performed 300 unilateral eccentric contractions (90°s-1) of the knee extensors. Prior to exercise, at 48-hours and at 96-hours after exercise, participants gave a venous blood sample and vastus lateralis biopsy and performed a maximal voluntary isometric knee extension. Skeletal muscle extracellular matrix content, and satellite cell content/proliferation were assessed by immunofluorescence. Transmission electron microscopy was used to quantify ultrastructural damage.Maximal isometric strength was comparable between T1D and their sex-matched control group prior to exercise for both sexes. Immediately following damaging exercise, strength was decreased in both groups but there was a moderate effect size for lower strength during recovery in the T1D group at both 48-hours and 96-hours. Serum creatine kinase, an indicator of muscle damage, was moderately higher in T1D participants compared to controls at rest, and exhibited a small elevation 96-hours after exercise. Immunofluorescence analyses showed satellite cell content was lower at all timepoints in those with type 1 diabetes. T1D participants demonstrated a moderate delay in satellite cell proliferation (as assessed by Pax7+/Ki67+ nuclei counts) after exercise, reaching peak levels of proliferation 48-hours after control participants. Despite these differences, those with T1D did not exhibit greater ultrastructural muscle damage than controls as assessed by electron microscopy. Finally, a transcriptomic investigation of T1D muscle revealed several networks of dysregulated genes involving RNA translation as well as mitochondrial respiration function, providing potential explanations for previous observations of mitochondrial dysfunction in similar T1D cohorts. Our novel findings indicate that skeletal muscle from physically active, young adults with moderately controlled T1D may have a reduced ability to handle, and repair from, damaging exercise. While larger cohort studies are clearly needed, these results suggest that those with T1D may require longer recovery times following damaging exercise.

Project description:BackgroundType 2 diabetes mellitus (T2DM) is a chronic disorder that is characterised by insulin resistance and hyperglycaemia, which over time may give rise to vascular complications. Resveratrol is a plant-derived nutritional supplement shown to have anti-diabetic properties in many animal models. Less evidence is available on its safety and efficacy in the management of T2DM in humans.ObjectivesTo assess the efficacy and safety of resveratrol formulations for adults with type 2 diabetes mellitus.Search methodsWe searched the Cochrane Central Register of Controlled Trials, MEDLINE, PubMed, Embase, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), and International Pharmaceutical Abstracts, as well as the International Clinical Trials Registry Platform (ICTRP) Search Portal and ClinicalTrials.gov. The date of the last search was December 2018 for all databases. No language restrictions were applied.Selection criteriaAll randomised controlled trials (RCTs) comparing effects of oral resveratrol (any dose or formulation, duration, or frequency of administration) with placebo, no treatment, other anti-diabetic medications, or diet or exercise, in adults with a diagnosis of T2DM.Data collection and analysisTwo review authors independently identified and included RCTs, assessed risk of bias, and extracted study-level data. Study authors were contacted for any missing information or for clarification of reported data. We assessed studies for certainty of the evidence using the GRADE instrument.Main resultsWe identified three RCTs with a total of 50 participants. Oral resveratrol not combined with other plant polyphenols was administered at 10 mg, 150 mg, or 1000 mg daily for a period ranging from four weeks to five weeks. The comparator intervention was placebo. Overall, all three included studies had low risk of bias. None of the three included studies reported long-term, patient-relevant outcomes such as all-cause mortality, diabetes-related complications, diabetes-related mortality, health-related quality of life, or socioeconomic effects. All three included studies reported that no adverse events were observed, indicating that no deaths occurred (very low-quality evidence for adverse events, all-cause mortality, and diabetes-related mortality). Resveratrol versus placebo showed neutral effects for glycosylated haemoglobin A1c (HbA1c) levels (mean difference (MD) 0.1%, 95% confidence interval (CI) -0.02 to 0.2; P = 0.09; 2 studies; 31 participants; very low-certainty evidence). Due to the short follow-up period, HbA1c results have to be interpreted cautiously. Similarly, resveratrol versus placebo showed neutral effects for fasting blood glucose levels (MD 2 mg/dL, 95% CI -2 to 7; P = 0.29; 2 studies; 31 participants), and resveratrol versus placebo showed neutral effects for insulin resistance (MD -0.35, 95% CI -0.99 to 0.28; P = 0.27; 2 studies; 36 participants). We found eight ongoing RCTs with approximately 800 participants and two studies awaiting assessment, which, when published, could contribute to the findings of this review.Authors' conclusionsCurrently, research is insufficient for review authors to evaluate the safety and efficacy of resveratrol supplementation for treatment of adults with T2DM. The limited available research does not provide sufficient evidence to support any effect, beneficial or adverse, of four to five weeks of 10 mg to 1000 mg of resveratrol in adults with T2DM. Adequately powered RCTs reporting patient-relevant outcomes with long-term follow-up periods are needed to further evaluate the efficacy and safety of resveratrol supplementation in the treatment of T2DM.

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Nicotine Metabolism in Adults With Type 2 Diabetes.

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Nicotine Metabolism in Adults With Type 2 Diabetes.

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