Journal Cover Diabetes Care
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   ISSN (Print) 0149-5992 - ISSN (Online) 1935-5548
   Published by American Diabetes Association Homepage  [4 journals]
  • Monocyte DPP4 Expression in Human Atherosclerosis Is Associated With
           Obesity and Dyslipidemia
    • Authors: Rao; X.; Deiuliis, J. A.; Mihai, G.; Varghese, J.; Xia, C.; Frieman, M. B.; Sztalryd, C.; Sun, X. J.; Quon, M. J.; Taylor, S. I.; Rajagopalan, S.; Zhong, J.
      Keywords: Complications-Macrovascular-Atherosclerotic Cardiovascular Disease and Human Diabetes
      PubDate: 2017-12-20T12:00:35-08:00
      DOI: 10.2337/dc17-0672
      Issue No: Vol. 41, No. 1 (2017)
  • Empagliflozin and Assessment of Lower-Limb Amputations in the EMPA-REG
           OUTCOME Trial
    • Authors: Inzucchi; S. E.; Iliev, H.; Pfarr, E.; Zinman, B.
      Keywords: Clinical Therapeutics/New Technology-Oral Agents
      PubDate: 2017-12-20T12:00:35-08:00
      DOI: 10.2337/dc17-1551
      Issue No: Vol. 41, No. 1 (2017)
  • Comment on Han et al. Comparative Effectiveness of Diabetic Oral
           Medications Among HIV-Infected and HIV-Uninfected Veterans. Diabetes Care
    • Authors: Garcia de Lucas; M. D.; Olalla Sierra, J.
      Keywords: Clinical Therapeutics/New Technology-Pharmacological Treatment of Complications
      PubDate: 2017-12-20T12:00:35-08:00
      DOI: 10.2337/dc17-1006
      Issue No: Vol. 41, No. 1 (2017)
  • Comment on Dubois-Laforgue et al. Diabetes, Associated Clinical Spectrum,
           Long-term Prognosis, and Genotype/Phenotype Correlations in 201 Adult
           Patients With Hepatocyte Nuclear Factor 1B (HNF1B) Molecular Defects.
           Diabetes Care 2017;40:1436-1443
    • Authors: Clissold; R. L.; Harries, L. W.; Ellard, S.; Bingham, C.; Hattersley, A. T.
      Keywords: Complications-Nephropathy-Clinical and Translational Research
      PubDate: 2017-12-20T12:00:35-08:00
      DOI: 10.2337/dc17-1672
      Issue No: Vol. 41, No. 1 (2017)
  • Response to Comment on Dubois-Laforgue et al. Diabetes, Associated
           Clinical Spectrum, Long-term Prognosis, and Genotype/Phenotype
           Correlations in 201 Adult Patients With Hepatocyte Nuclear Factor 1B
           (HNF1B) Molecular Defects. Diabetes Care 2017;40:1436-1443
    • Authors: Dubois-Laforgue; D.; Cornu, E.; Saint-Martin, C.; Coste, J.; Bellanne-Chantelot, C.; Timsit, J.
      Keywords: Genetics-Type 2 Diabetes
      PubDate: 2017-12-20T12:00:35-08:00
      DOI: 10.2337/dci17-0048
      Issue No: Vol. 41, No. 1 (2017)
  • In This Issue of Diabetes Care
    • Pages: 1 - 2
      PubDate: 2017-12-20T12:00:35-08:00
      DOI: 10.2337/dc18-ti01
      Issue No: Vol. 41, No. 1 (2017)
  • In an Anniversary Year, Diabetes Care Takes a Selfie
    • Authors: Riddle; M. C.
      Pages: 3 - 5
      Keywords: Health Care Delivery-Economics
      PubDate: 2017-12-20T12:00:35-08:00
      DOI: 10.2337/dci17-0054
      Issue No: Vol. 41, No. 1 (2017)
  • Lower Risk of Death With SGLT2 Inhibitors in Observational Studies: Real
           or Bias'
    • Authors: Suissa; S.
      Pages: 6 - 10
      Abstract: Two recent observational studies reported a remarkably lower rate of all-cause death associated with sodium–glucose cotransporter 2 inhibitor (­SGLT2i) use in all patients with type 2 diabetes and not only those at increased cardiovascular risk. The >50% lower mortality rates reported in these studies are much greater than those found in the BI 10773 (Empagliflozin) Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients (EMPA-REG OUTCOME) and CANagliflozin cardioVascular Assessment Study (CANVAS) randomized trials. We show that these observational studies are affected by time-related biases, including immortal time bias and time-lag bias, which tend to exaggerate the benefits observed with a drug. The Comparative Effectiveness of Cardiovascular Outcomes in New Users of SGLT-2 Inhibitors (CVD-REAL) study, based on 166,033 users of SGLT2i and 1,226,221 users of other glucose-lowering drugs (oGLD) identified from health care databases of six countries, was affected by immortal time bias. Indeed, the immortal time between the first oGLD prescription and the first SGLT2i prescription was omitted from the analysis, which resulted in increasing the rate of death in the oGLD group and thus producing the appearance of a lower risk of death with SGLT2i use. The Swedish study compared 10,879 SGLT2i/dipeptidyl peptidase 4 inhibitor (DPP-4i) users with 10,879 matched insulin users. Such comparisons involving second-line therapies with a third-line therapy can introduce time-lag bias, as the patients may not be at the same stage of diabetes. This bias is compounded by the fact that the users of insulin had already started their insulin before cohort entry, unlike the new users of SGLT2i. Finally, the study also introduces immortal time bias with respect to the effects of SGLT2i relative to DPP-4i. In conclusion, the >50% lower rate of death with SGLT2i in type 2 diabetes reported by two recent observational studies is likely exaggerated by immortal time and time-lag biases. It thus remains uncertain whether the benefit seen with empagliflozin in the EMPA-REG OUTCOME trial applies to all SGLT2i and to all patients with type 2 diabetes, not only those at increased cardiovascular risk. While observational studies can provide crucial real-world evidence for the effects of medications, they need to be carefully conducted to avoid such major time-related biases.
      Keywords: Epidemiology-Other
      PubDate: 2017-12-20T12:00:35-08:00
      DOI: 10.2337/dc17-1223
      Issue No: Vol. 41, No. 1 (2017)
  • Heart Failure: The Most Important, Preventable, and Treatable
           Cardiovascular Complication of Type 2 Diabetes
    • Authors: Packer; M.
      Pages: 11 - 13
      Keywords: Complications-Hypoglycemia, Heart Failure
      PubDate: 2017-12-20T12:00:35-08:00
      DOI: 10.2337/dci17-0052
      Issue No: Vol. 41, No. 1 (2017)
  • Cardiovascular Outcomes Trials in Type 2 Diabetes: Where Do We Go From
           Here' Reflections From a Diabetes Care Editors Expert Forum
    • Authors: Cefalu; W. T.; Kaul, S.; Gerstein, H. C.; Holman, R. R.; Zinman, B.; Skyler, J. S.; Green, J. B.; Buse, J. B.; Inzucchi, S. E.; Leiter, L. A.; Raz, I.; Rosenstock, J.; Riddle, M. C.
      Pages: 14 - 31
      Abstract: In December 2008, the U.S. Food and Drug Administration issued guidance to the pharmaceutical industry setting new expectations for the development of antidiabetes drugs for type 2 diabetes. This guidance expanded the scope and cost of research necessary for approval of such drugs by mandating long-term cardiovascular outcomes trials (CVOTs) for safety. Since 2008, 9 CVOTs have been reported, 13 are under way, and 4 have been terminated. Reassuringly, each of the completed trials demonstrated the noninferiority of their respective drugs to placebo for their primary cardiovascular (CV) composite end point. Notably, four additionally provided evidence of CV benefit in the form of significant decreases in the primary CV composite end point, two suggested reductions in CV death, and three suggested reductions in all-cause mortality. Although these trials have yielded much valuable information, whether that information justifies the investment of time and resources is controversial. In June 2016, a Diabetes Care Editors’ Expert Forum convened to review the processes and challenges of CVOTs, discuss the benefits and limitations of their current designs, and weigh the merits of modifications that might improve the efficiency and clinical value of future trials. Discussion and analysis continued with the CVOT trial results released in June 2017 at the American Diabetes Association’s Scientific Sessions and in September 2017 at the European Association for the Study of Diabetes scientific meeting. This article summarizes the discussion and findings to date.
      Keywords: Diabetes Education, Heart Failure, Diabetes Care Expert Forum
      PubDate: 2017-12-20T12:00:35-08:00
      DOI: 10.2337/dci17-0057
      Issue No: Vol. 41, No. 1 (2017)
  • Severity of Neuropathy Is Associated With Long-term Spinal Cord
           Stimulation Outcome in Painful Diabetic Peripheral Neuropathy: Five-Year
           Follow-up of a Prospective Two-Center Clinical Trial
    • Authors: van Beek; M.; Geurts, J. W.; Slangen, R.; Schaper, N. C.; Faber, C. G.; Joosten, E. A.; Dirksen, C. D.; van Dongen, R. T.; van Kuijk, S. M. J.; van Kleef, M.
      Pages: 32 - 38
      Abstract: OBJECTIVEEvidence from prospective studies for long-term treatment efficacy of spinal cord stimulation (SCS) in painful diabetic peripheral neuropathy (PDPN) is not available. We report prospective data on the effect of SCS on pain ratings, treatment success and failure, and complications during a 5-year follow-up in patients with PDPN.RESEARCH DESIGN AND METHODSPatients with PDPN (n = 48) were included in this prospective multicenter study. The Michigan Diabetic Neuropathy Score (MDNS) was used to assess the severity of neuropathy. Numerical rating scale (NRS) score for pain, Patient’s Global Impression of Change (PGIC), and treatment success (50% reduction of NRS score or significant PGIC) during 5 years of follow-up were evaluated. Complications of SCS were reported, and associations between baseline characteristics and SCS trial success or failure during a 5-year follow-up were investigated by using survival analyses.RESULTSTreatment success was observed in 55% of patients after 5 years. Median duration of SCS treatment was 60 months (minimum 1 month, maximum 60 months), and 80% of patients with a permanent implant still used their SCS device after 5 years. Higher MDNS was associated with treatment failure during the 5-year follow-up (hazard ratio 3.9 [95% CI 1.3–11.6]; P = 0.014).CONCLUSIONSSCS is successful in reducing chronic pain symptoms in the lower extremities of patients with PDPN up to 5 years after initiation of treatment. Furthermore, 80% of patients with PDPN still use their SCS device after 5 years. Moreover, the severity of neuropathy is associated with a higher chance of long-term treatment failure during a 5-year follow-up.
      Keywords: Complications-Neuropathy
      PubDate: 2017-12-20T12:00:35-08:00
      DOI: 10.2337/dc17-0983
      Issue No: Vol. 41, No. 1 (2017)
  • Prospective Postmarketing Surveillance of Acute Myocardial Infarction in
           New Users of Saxagliptin: A Population-Based Study
    • Authors: Toh; S.; Reichman, M. E.; Graham, D. J.; Hampp, C.; Zhang, R.; Butler, M. G.; Iyer, A.; Rucker, M.; Pimentel, M.; Hamilton, J.; Lendle, S.; Fireman, B. H.; for the Mini-Sentinel Saxagliptin-AMI Surveillance Writing Group
      Pages: 39 - 48
      Abstract: OBJECTIVEThe cardiovascular safety of saxagliptin, a dipeptidyl-peptidase 4 inhibitor, compared with other antihyperglycemic treatments is not well understood. We prospectively examined the association between saxagliptin use and acute myocardial infarction (AMI).RESEARCH DESIGN AND METHODSWe identified patients aged ≥18 years, starting from the approval date of saxagliptin in 2009 and continuing through August 2014, using data from 18 Mini-Sentinel data partners. We conducted seven sequential assessments comparing saxagliptin separately with sitagliptin, pioglitazone, second-generation sulfonylureas, and long-acting insulin, using disease risk score (DRS) stratification and propensity score (PS) matching to adjust for potential confounders. Sequential testing kept the overall chance of a false-positive signal below 0.05 (one-sided) for each pairwise comparison.RESULTSWe identified 82,264 saxagliptin users and more than 1.5 times as many users of each comparator. At the end of surveillance, the DRS-stratified hazard ratios (HRs) (95% CI) were 1.08 (0.90–1.28) in the comparison with sitagliptin, 1.11 (0.87–1.42) with pioglitazone, 0.79 (0.64–0.98) with sulfonylureas, and 0.57 (0.46–0.70) with long-acting insulin. The corresponding PS-matched HRs were similar. Only one interim analysis of 168 analyses met criteria for a safety signal: the PS-matched saxagliptin-pioglitazone comparison from the fifth sequential analysis, which yielded an HR of 1.63 (1.12–2.37). This association diminished in subsequent analyses.CONCLUSIONSWe did not find a higher AMI risk in saxagliptin users compared with users of other selected antihyperglycemic agents during the first 5 years after U.S. Food and Drug Administration approval of the drug.
      Keywords: Epidemiology-Cardiovascular Disease
      PubDate: 2017-12-20T12:00:35-08:00
      DOI: 10.2337/dc17-0476
      Issue No: Vol. 41, No. 1 (2017)
  • Five-Year Effectiveness of the Multidisciplinary Risk Assessment and
           Management Programme-Diabetes Mellitus (RAMP-DM) on Diabetes-Related
           Complications and Health Service Uses--A Population-Based and
           Propensity-Matched Cohort Study
    • Authors: Wan; E. Y. F.; Fung, C. S. C.; Jiao, F. F.; Yu, E. Y. T.; Chin, W. Y.; Fong, D. Y. T.; Wong, C. K. H.; Chan, A. K. C.; Chan, K. H. Y.; Kwok, R. L. P.; Lam, C. L. K.
      Pages: 49 - 59
      Abstract: OBJECTIVETo evaluate the 5-year effectiveness of a multidisciplinary Risk Assessment and Management Programme–Diabetes Mellitus (RAMP-DM) in primary care patients with type 2 diabetes.RESEARCH DESIGN AND METHODSA 5-year prospective cohort study was conducted with 121,584 Chinese primary care patients with type 2 DM who were recruited between August 2009 and June 2011. Missing data were dealt with multiple imputations. After excluding patients with prior diabetes mellitus (DM)-related complications and one-to-one propensity score matching on all patient characteristics, 26,718 RAMP-DM participants and 26,718 matched usual care patients were followed up for a median time of 4.5 years. The effect of RAMP-DM on nine DM-related complications and all-cause mortality were evaluated using Cox regressions. The first incidence for each event was used for all models. Health service use was analyzed using negative binomial regressions. Subgroup analyses on different patient characteristics were performed.RESULTSThe cumulative incidence of all events (DM-related complications and all-cause mortality) was 23.2% in the RAMP-DM group and 43.6% in the usual care group. RAMP-DM led to significantly greater reductions in cardiovascular disease (CVD) risk by 56.6% (95% CI 54.5, 58.6), microvascular complications by 11.9% (95% CI 7.0, 16.6), mortality by 66.1% (95% CI 64.3, 67.9), specialist attendance by 35.0% (95% CI 33.6, 36.4), emergency attendance by 41.2% (95% CI 39.8, 42.5), and hospitalizations by 58.5% (95% CI 57.2, 59.7). Patients with low baseline CVD risks benefitted the most from RAMP-DM, which decreased CVD and mortality risk by 60.4% (95% CI 51.8, 67.5) and 83.6% (95% CI 79.3, 87.0), respectively.CONCLUSIONSThis naturalistic study highlighted the importance of early optimal DM control and risk factor management by risk stratification and multidisciplinary, protocol-driven, chronic disease model care to delay disease progression and prevent complications.
      Keywords: Epidemiology-Diabetes Complications
      PubDate: 2017-12-20T12:00:35-08:00
      DOI: 10.2337/dc17-0426
      Issue No: Vol. 41, No. 1 (2017)
  • Prediction of Type 2 Diabetes by Hemoglobin A1c in Two Community-Based
    • Authors: Leong; A.; Daya, N.; Porneala, B.; Devlin, J. J.; Shiffman, D.; McPhaul, M. J.; Selvin, E.; Meigs, J. B.
      Pages: 60 - 68
      Abstract: OBJECTIVEHemoglobin A1c (HbA1c) can be used to assess type 2 diabetes (T2D) risk. We asked whether HbA1c was associated with T2D risk in four scenarios of clinical information availability: 1) HbA1c alone, 2) fasting laboratory tests, 3) clinic data, and 4) fasting laboratory tests and clinic data.RESEARCH DESIGN AND METHODSWe studied a prospective cohort of white (N = 11,244) and black (N = 2,294) middle-aged participants without diabetes in the Framingham Heart Study and Atherosclerosis Risk in Communities study. Association of HbA1c with incident T2D (defined by medication use or fasting glucose [FG] ≥126 mg/dL) was evaluated in regression models adjusted for 1) age and sex (demographics); 2) demographics, FG, HDL, and triglycerides; 3) demographics, BMI, blood pressure, and T2D family history; or 4) all preceding covariates. We combined results from cohort and race analyses by random-effects meta-analyses. Subsidiary analyses tested the association of HbA1c with developing T2D within 8 years or only after 8 years.RESULTSOver 20 years, 3,315 individuals developed T2D. With adjustment for demographics, the odds of T2D increased fourfold for each percentage-unit increase in HbA1c. The odds ratio (OR) was 4.00 (95% CI 3.14, 5.10) for blacks and 4.73 (3.10, 7.21) for whites, resulting in a combined OR of 4.50 (3.35, 6.03). After adjustment for fasting laboratory tests and clinic data, the combined OR was 2.68 (2.15, 3.34) over 20 years, 5.79 (2.51, 13.36) within 8 years, and 2.23 (1.94, 2.57) after 8 years.CONCLUSIONSHbA1c predicts T2D in different common scenarios and is useful for identifying individuals with elevated T2D risk in both the short- and long-term.
      Keywords: Epidemiology-Clinical-Diagnosis and Screening
      PubDate: 2017-12-20T12:00:35-08:00
      DOI: 10.2337/dc17-0607
      Issue No: Vol. 41, No. 1 (2017)
  • Long-term Trends in Antidiabetes Drug Usage in the U.S.: Real-world
           Evidence in Patients Newly Diagnosed With Type 2 Diabetes
    • Authors: Montvida; O.; Shaw, J.; Atherton, J. J.; Stringer, F.; Paul, S. K.
      Pages: 69 - 78
      Abstract: OJBECTIVETo explore temporal trends in antidiabetes drug (ADD) prescribing and intensification patterns, along with glycemic levels and comorbidities, and possible benefits of novel ADDs in delaying the need for insulin initiation in patients diagnosed with type 2 diabetes.RESEARCH DESIGN AND METHODSPatients with type 2 diabetes aged 18–80 years, who initiated any ADD, were selected (n = 1,023,340) from the U.S. Centricity Electronic Medical Records. Those who initiated second-line ADD after first-line metformin were identified (subcohort 1, n = 357,482); the third-line therapy choices were further explored.RESULTSFrom 2005 to 2016, first-line use increased for metformin (60–77%) and decreased for sulfonylureas (20–8%). During a mean follow-up of 3.4 years post metformin, 48% initiated a second ADD at a mean HbA1c of 8.4%. In subcohort 1, although sulfonylurea usage as second-line treatment decreased (60–46%), it remained the most popular second ADD choice. Use increased for insulin (7–17%) and dipeptidyl peptidase-4 inhibitors (DPP-4i) (0.4–21%). The rates of intensification with insulin and sulfonylureas did not decline over the last 10 years. The restricted mean time to insulin initiation was marginally longer in second-line DPP-4i (7.1 years) and in the glucagon-like peptide 1 receptor agonist group (6.6 years) compared with sulfonylurea (6.3 years, P < 0.05).CONCLUSIONSMost patients initiate second-line therapy at elevated HbA1c levels, with highly heterogeneous clinical characteristics across ADD classes. Despite the introduction of newer therapies, sulfonylureas remained the most popular second-line agent, and the rates of intensification with sulfonylureas and insulin remained consistent over time. The incretin-based therapies were associated with a small delay in the need for therapy intensification compared with sulfonylureas.
      Keywords: Clinical Therapeutics/New Technology-Pharmacological Treatment of Complications
      PubDate: 2017-12-20T12:00:35-08:00
      DOI: 10.2337/dc17-1414
      Issue No: Vol. 41, No. 1 (2017)
  • N-Glycan Profile and Kidney Disease in Type 1 Diabetes
    • Authors: Bermingham; M. L.; Colombo, M.; McGurnaghan, S. J.; Blackbourn, L. A. K.; Vuckovic, F.; Pucic Bakovic, M.; Trbojevic-Akmacic, I.; Lauc, G.; Agakov, F.; Agakova, A. S.; Hayward, C.; Klaric, L.; Palmer, C. N. A.; Petrie, J. R.; Chalmers, J.; Collier, A.; Green, F.; Lindsay, R. S.; Macrury, S.; McKnight, J. A.; Patrick, A. W.; Thekkepat, S.; Gornik, O.; McKeigue, P. M.; Colhoun, H. M.; on behalf of the SDRN Type 1 Bioresource Investigators
      Pages: 79 - 87
      Abstract: OBJECTIVEPoorer glycemic control in type 1 diabetes may alter N-glycosylation patterns on circulating glycoproteins, and these alterations may be linked with diabetic kidney disease (DKD). We investigated associations between N-glycans and glycemic control and renal function in type 1 diabetes.RESEARCH DESIGN AND METHODSUsing serum samples from 818 adults who were considered to have extreme annual loss in estimated glomerular filtration rate (eGFR; i.e., slope) based on retrospective clinical records, from among 6,127 adults in the Scottish Diabetes Research Network Type 1 Bioresource Study, we measured total and IgG-specific N-glycan profiles. This yielded a relative abundance of 39 total (GP) and 24 IgG (IGP) N-glycans. Linear regression models were used to investigate associations between N-glycan structures and HbA1c, albumin-to-creatinine ratio (ACR), and eGFR slope. Models were adjusted for age, sex, duration of type 1 diabetes, and total serum IgG.RESULTSHigher HbA1c was associated with a lower relative abundance of simple biantennary N-glycans and a higher relative abundance of more complex structures with more branching, galactosylation, and sialylation (GP12, 26, 31, 32, and 34, and IGP19 and 23; all P < 3.79 x 10–4). Similar patterns were seen for ACR and greater mean annual loss of eGFR, which were also associated with fewer of the simpler N-glycans (all P < 3.79 x 10–4).CONCLUSIONSHigher HbA1c in type 1 diabetes is associated with changes in the serum N-glycome that have elsewhere been shown to regulate the epidermal growth factor receptor and transforming growth factor-β pathways that are implicated in DKD. Furthermore, N-glycans are associated with ACR and eGFR slope. These data suggest that the role of altered N-glycans in DKD warrants further investigation.
      Keywords: Complications-Nephropathy-Basic and Experimental Science
      PubDate: 2017-12-20T12:00:35-08:00
      DOI: 10.2337/dc17-1042
      Issue No: Vol. 41, No. 1 (2017)
  • Diabetes Care Disparities in Long-standing Type 1 Diabetes in Canada and
           the U.S.: A Cross-sectional Comparison
    • Authors: Weisman; A.; Lovblom, L. E.; Keenan, H. A.; Tinsley, L. J.; DEon, S.; Boulet, G.; Farooqi, M. A.; Lovshin, J. A.; Orszag, A.; Lytvyn, Y.; Brent, M. H.; Paul, N.; Bril, V.; Cherney, D. Z.; Perkins, B. A.
      Pages: 88 - 95
      Abstract: OBJECTIVETo assess national differences in diabetes care and quality of life (QOL) between individuals with long-standing type 1 diabetes (≥50 years) in Canada and the U.S.RESEARCH DESIGN AND METHODSCross-sectional data from identical surveys administered in the Canadian Study of Longevity in Diabetes and the Joslin Medalist Study, collected in 2013–2016 and 2005–2011, respectively, were compared. Laboratory values and ophthalmic examination were completed by clinical care physicians for Canadians and the Joslin Clinic for Americans. Univariate comparisons and multivariable regression for HbA1c, QOL, insulin pump use, and coronary artery disease (CAD) were performed. Nephropathy, CAD, and peripheral arterial disease (PAD) were self-reported; neuropathy was defined by a Michigan Neuropathy Screening Instrument (Questionnaire component) score ≥3, and proliferative retinopathy was documented from ophthalmic examination. QOL was self-reported on an ordinal scale.RESULTSThree hundred sixty-one Canadians and 668 Americans had similar ages (mean 65.78 years [SD 8.67] vs. 66.38 years [7.66], P = 0.27) and durations of diabetes (median 53.00 years [interquartile range 51.00, 58.00] vs. 53.00 years [51.00, 57.00], P = 0.51). Canadians had higher HbA1c (mean 7.53% [SD 1.03] [59 mmol/mol] vs. 7.22% [0.98] [55 mmol/mol], P < 0.0001), lower QOL (36.9% vs. 48.7% with "excellent" QOL, P = 0.0002), and less CAD (29.7% vs. 41.2%, P = 0.0003) and insulin pump use (43.3% vs. 55.6%, P = 0.0002). Other complication rates were similar. Residual differences for Canadians compared with Americans remained after adjustment for age, sex, CAD, PAD, education, and relevant a priori selected variables: 0.28% higher HbA1c (P = 0.0004); and odds ratios of 0.68 (95% CI 0.51, 0.90), 0.46 (0.31, 0.68), and 0.71 (0.52, 0.96) for higher QOL, CAD, and insulin pump use, respectively.CONCLUSIONSAlthough Canadians and Americans have similar rates of complications other than CAD, further research is required to understand why Canadians have higher HbA1c levels, lower QOL, and less insulin pump use.
      Keywords: Epidemiology-Type 1 Diabetes
      PubDate: 2017-12-20T12:00:35-08:00
      DOI: 10.2337/dc17-1074
      Issue No: Vol. 41, No. 1 (2017)
  • The Effect of Telemedicine Follow-up Care on Diabetes-Related Foot Ulcers:
           A Cluster-Randomized Controlled Noninferiority Trial
    • Authors: Smith-Strom; H.; Igland, J.; Ostbye, T.; Tell, G. S.; Hausken, M. F.; Graue, M.; Skeie, S.; Cooper, J. G.; Iversen, M. M.
      Pages: 96 - 103
      Abstract: OBJECTIVETo evaluate whether telemedicine (TM) follow-up of patients with diabetes-related foot ulcers (DFUs) in primary health care in collaboration with specialist health care was noninferior to standard outpatient care (SOC) for ulcer healing time. Further, we sought to evaluate whether the proportion of amputations, deaths, number of consultations per month, and patient satisfaction differed between the two groups.RESEARCH DESIGN AND METHODSPatients with DFUs were recruited from three clinical sites in western Norway (2012–2016). The cluster-randomized controlled noninferiority trial included 182 adults (94/88 in the TM/SOC groups) in 42 municipalities/districts. The intervention group received TM follow-up care in the community; the control group received SOC. The primary end point was healing time. Secondary end points were amputation, death, number of consultations per month, and patient satisfaction.RESULTSUsing mixed-effects regression analysis, we found that TM was noninferior to SOC regarding healing time (mean difference –0.43 months, 95% CI –1.50, 0.65). When competing risk from death and amputation were taken into account, there was no significant difference in healing time between the groups (subhazard ratio 1.16, 95% CI 0.85, 1.59). The TM group had a significantly lower proportion of amputations (mean difference –8.3%, 95% CI –16.3%, –0.5%), and there were no significant differences in the proportion of deaths, number of consultations, or patient satisfaction between groups, although the direction of the effect estimates for these clinical outcomes favored the TM group.CONCLUSIONSThe results suggest that use of TM technology can be a relevant alternative and supplement to usual care, at least for patients with more superficial ulcers.
      Keywords: Foot Care-Lower Extremities
      PubDate: 2017-12-20T12:00:35-08:00
      DOI: 10.2337/dc17-1025
      Issue No: Vol. 41, No. 1 (2017)
  • The Association of Severe Hypoglycemia With Incident Cardiovascular Events
           and Mortality in Adults With Type 2 Diabetes
    • Authors: Lee; A. K.; Warren, B.; Lee, C. J.; McEvoy, J. W.; Matsushita, K.; Huang, E. S.; Sharrett, A. R.; Coresh, J.; Selvin, E.
      Pages: 104 - 111
      Abstract: OBJECTIVEThere is suggestive evidence linking hypoglycemia with cardiovascular disease, but few data have been collected in a community-based setting. Information is lacking on individual cardiovascular outcomes and cause-specific mortality.RESEARCH DESIGN AND METHODSWe conducted a prospective cohort analysis of 1,209 participants with diagnosed diabetes from the Atherosclerosis Risk in Communities (ARIC) study (analytic baseline, 1996–1998). Severe hypoglycemic episodes were identified using first position ICD-9 codes from hospitalizations, emergency department visits, and ambulance calls through 2013. Cardiovascular events and deaths were captured through 2013. We used adjusted Cox regression models with hypoglycemia as a time-varying exposure.RESULTSThere were 195 participants with at least one severe hypoglycemic episode during a median fellow-up of 15.3 years. After severe hypoglycemia, the 3-year cumulative incidence of coronary heart disease was 10.8% and of mortality was 28.3%. After adjustment, severe hypoglycemia was associated with coronary heart disease (hazard ratio [HR] 2.02, 95% CI 1.27–3.20), all-cause mortality (HR 1.73, 95% CI 1.38–2.17), cardiovascular mortality (HR 1.64, 95% CI 1.15–2.34), and cancer mortality (HR 2.49, 95% CI 1.46–4.24). Hypoglycemia was not associated with stroke, heart failure, atrial fibrillation, or noncardiovascular and noncancer death. Results were robust within subgroups defined by age, sex, race, diabetes duration, and baseline cardiovascular risk.CONCLUSIONSSevere hypoglycemia is clearly indicative of declining health and is a potent marker of high absolute risk of cardiovascular events and mortality.
      Keywords: Complications-Hypoglycemia
      PubDate: 2017-12-20T12:00:35-08:00
      DOI: 10.2337/dc17-1669
      Issue No: Vol. 41, No. 1 (2017)
  • Hyperbaric Oxygen Therapy in the Treatment of Ischemic Lower- Extremity
           Ulcers in Patients With Diabetes: Results of the DAMO2CLES Multicenter
           Randomized Clinical Trial
    • Authors: Santema; K. T. B.; Stoekenbroek, R. M.; Koelemay, M. J. W.; Reekers, J. A.; van Dortmont, L. M. C.; Oomen, A.; Smeets, L.; Wever, J. J.; Legemate, D. A.; Ubbink, D. T.; on behalf of the DAMO2CLES Study Group
      Pages: 112 - 119
      Abstract: OBJECTIVEConflicting evidence exists on the effects of hyperbaric oxygen therapy (HBOT) in the treatment of chronic ischemic leg ulcers. The aim of this trial was to investigate whether additional HBOT would benefit patients with diabetes and ischemic leg ulcers.RESEARCH DESIGN AND METHODSPatients with diabetes with an ischemic wound (n = 120) were randomized to standard care (SC) without or with HBOT (SC+HBOT). Primary outcomes were limb salvage and wound healing after 12 months, as well as time to wound healing. Other end points were amputation-free survival (AFS) and mortality.RESULTSBoth groups contained 60 patients. Limb salvage was achieved in 47 patients in the SC group vs. 53 patients in the SC+HBOT group (risk difference [RD] 10% [95% CI –4 to 23]). After 12 months, 28 index wounds were healed in the SC group vs. 30 in the SC+HBOT group (RD 3% [95% CI –14 to 21]). AFS was achieved in 41 patients in the SC group and 49 patients in the SC+HBOT group (RD 13% [95% CI –2 to 28]). In the SC+HBOT group, 21 patients (35%) were unable to complete the HBOT protocol as planned. Those who did had significantly fewer major amputations and higher AFS (RD for AFS 26% [95% CI 10–38]).CONCLUSIONSAdditional HBOT did not significantly improve complete wound healing or limb salvage in patients with diabetes and lower-limb ischemia.
      Keywords: Complications-Macrovascular-Atherosclerotic Cardiovascular Disease and Human Diabetes
      PubDate: 2017-12-20T12:00:35-08:00
      DOI: 10.2337/dc17-0654
      Issue No: Vol. 41, No. 1 (2017)
  • Subclinical First Trimester Renal Abnormalities Are Associated With
           Preeclampsia in Normoalbuminuric Women With Type 1 Diabetes
    • Authors: Kelly; C. B.; Hookham, M. B.; Yu, J. Y.; Jenkins, A. J.; Nankervis, A. J.; Hanssen, K. F.; Garg, S. K.; Scardo, J. A.; Hammad, S. M.; Menard, M. K.; Aston, C. E.; Lyons, T. J.
      Pages: 120 - 127
      Abstract: OBJECTIVEThis study was conducted to determine the utility of tubular (urinary/plasma neutrophil gelatinase-associated lipocalin [NGAL] and urinary kidney injury molecule 1 [KIM-1]) and glomerular (estimated glomerular filtration rate [eGFR]) biomarkers in predicting preeclampsia (PE) in pregnant women with type 1 diabetes mellitus (T1DM) who were free of microalbuminuria and hypertension at the first trimester.RESEARCH DESIGN AND METHODSThis was a prospective study of T1DM pregnancy. Maternal urinary and plasma NGAL, urinary KIM-1 (ELISA of frozen samples), and eGFR (Chronic Kidney Disease Epidemiology Collaboration equation) were determined at three study visits (V1: 12.4 ± 1.8; V2: 21.7 ± 1.4; V3: 31.4 ± 1.5 weeks’ gestation [mean ± SD]) in 23 women with T1DM with subsequent PE (DM+PE+), 24 who remained normotensive (DM+PE–), and, for reference, in 19 normotensive pregnant women without diabetes (DM–). The groups with diabetes were matched for age, diabetes duration, and parity. All subjects were normotensive and free of microalbuminuria or albuminuria at V1. All study visits preceded the onset of PE.RESULTSUrinary creatinine-corrected NGAL (uNGALcc, ng/mg) was significantly elevated at V1 in DM+PE+ vs. DM+PE– women (P = 0.01); this remained significant after exclusion of leukocyte-positive samples (5 DM+PE+ and 2 DM+PE–) (P = 0.02). Accounting for BMI, HbA1c, and total daily insulin dose, a doubling of uNGALcc at V1 conferred a sevenfold increase in risk for PE (P = 0.026). In contrast, neither plasma NGAL nor urinary KIM-1 predicted PE. Also at V1, eGFR was elevated in DM+PE+ vs. DM+PE– (P = 0.04).CONCLUSIONSEarly tubular and glomerular dysfunction may predict PE in first trimester women with T1DM, even if free of microalbuminuria. These data suggest that subclinical renal tubular and glomerular injury, if present early in pregnancy, may predispose women with T1DM to PE.
      Keywords: Pregnancy-Basic Science/Translational
      PubDate: 2017-12-20T12:00:35-08:00
      DOI: 10.2337/dc17-1635
      Issue No: Vol. 41, No. 1 (2017)
  • Association Between Inflammatory Markers and Progression to Kidney
           Dysfunction: Examining Different Assessment Windows in Patients With Type
           1 Diabetes
    • Authors: Baker; N. L.; Hunt, K. J.; Stevens, D. R.; Jarai, G.; Rosen, G. D.; Klein, R. L.; Virella, G.; Lopes-Virella, M. F.; the DCCT/EDIC Research Group
      Pages: 128 - 135
      Abstract: OBJECTIVETo determine whether biomarkers of inflammation and endothelial dysfunction are associated with the development of kidney dysfunction and the time frame of their association.RESEARCH DESIGN AND METHODSBiomarkers were measured at four time points during 28 years of treatment and follow-up in patients with type 1 diabetes in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) cohort. In addition to traditional biomarkers of inflammation (C-reactive protein and fibrinogen), we measured interleukin-6 (IL-6) and soluble tumor necrosis factor receptors 1 and 2 (sTNFR-1/2), markers of endothelial dysfunction (soluble intracellular adhesion molecule-1, vascular cell adhesion molecule-1, and E-selectin [sE-selectin]), and fibrinolysis (total and active plasminogen activator inhibitor-1 [PAI-1]). Renal outcomes were defined as progression to incident chronic kidney disease (stage 3 or more severe) or macroalbuminuria (albumin excretion rate ≥300 mg/24 h). Prospective multivariate event-time analyses were used to determine the association of each biomarker with each subsequent event within prespecified intervals (3-year and 10-year windows).RESULTSMultivariate event-time models indicated that several markers of inflammation (sTNFR-1/2), endothelial dysfunction (sE-selectin), and clotting/fibrinolysis (fibrinogen and PAI-1) are significantly associated with subsequent development of kidney dysfunction. Although some markers showed variations in the associations between the follow-up windows examined, the results indicate that biomarkers (sTNFR-1/2, sE-selectin, PAI-1, and fibrinogen) are associated with progression to chronic kidney disease in both the 3-year and the 10-year windows.CONCLUSIONSPlasma markers of inflammation, endothelial dysfunction, and clotting/fibrinolysis are associated with progression to kidney dysfunction in type 1 diabetes during both short-term and long-term follow-up.
      Keywords: Complications-Nephropathy-Clinical and Translational Research
      PubDate: 2017-12-20T12:00:35-08:00
      DOI: 10.2337/dc17-0867
      Issue No: Vol. 41, No. 1 (2017)
  • Mortality Reduction Associated With {beta}-Adrenoceptor Inhibition in
           Chronic Heart Failure Is Greater in Patients With Diabetes
    • Authors: Witte; K. K.; Drozd, M.; Walker, A. M. N.; Patel, P. A.; Kearney, J. C.; Chapman, S.; Sapsford, R. J.; Gierula, J.; Paton, M. F.; Lowry, J.; Kearney, M. T.; Cubbon, R. M.
      Pages: 136 - 142
      Abstract: OBJECTIVEDiabetes increases mortality in patients with chronic heart failure (CHF) and reduced left ventricular ejection fraction. Studies have questioned the safety of β-adrenoceptor blockers (β-blockers) in some patients with diabetes and reduced left ventricular ejection fraction. We examined whether β-blockers and ACE inhibitors (ACEIs) are associated with differential effects on mortality in CHF patients with and without diabetes.RESEARCH DESIGN AND METHODSWe conducted a prospective cohort study of 1,797 patients with CHF recruited between 2006 and 2014, with mean follow-up of 4 years. β-Blocker dose was expressed as the equivalent dose of bisoprolol (mg/day) and ACEI dose as the equivalent dose of ramipril (mg/day). Cox regression analysis was used to examine the interaction between diabetes and drug dose on all-cause mortality.RESULTSPatients with diabetes were prescribed larger doses of β-blockers and ACEIs than were patients without diabetes. Increasing β-blocker dose was associated with lower mortality in patients with diabetes (8.9% per mg/day; 95% CI 5–12.6) and without diabetes (3.5% per mg/day; 95% CI 0.7–6.3), although the effect was larger in people with diabetes (interaction P = 0.027). Increasing ACEI dose was associated with lower mortality in patients with diabetes (5.9% per mg/day; 95% CI 2.5–9.2) and without diabetes (5.1% per mg/day; 95% CI 2.6–7.6), with similar effect size in these groups (interaction P = 0.76).CONCLUSIONSIncreasing β-blocker dose is associated with a greater prognostic advantage in CHF patients with diabetes than in CHF patients without diabetes.
      Keywords: Clinical Therapeutics/New Technology-Pharmacological Treatment of Complications, Heart Failure
      PubDate: 2017-12-20T12:00:35-08:00
      DOI: 10.2337/dc17-1406
      Issue No: Vol. 41, No. 1 (2017)
  • Short- and Long-term Prognosis of Patients With Acute Heart Failure With
           and Without Diabetes: Changes Over the Last Three Decades
    • Authors: van den Berge; J. C.; Constantinescu, A. A.; Boiten, H. J.; van Domburg, R. T.; Deckers, J. W.; Akkerhuis, K. M.
      Pages: 143 - 149
      Abstract: OBJECTIVEWe studied differences in long-term (i.e., 10 year) prognosis among patients with acute heart failure (HF) with and without diabetes over the last three decades. In addition, we investigated whether the degree of prognostic improvement in that period was comparable between patients with and without diabetes.RESEARCH DESIGN AND METHODSThis prospective registry included all consecutive patients aged 18 years and older admitted to the Intensive Coronary Care Unit with acute HF in the period of 1985–2008. A total of 1,810 patients were included; 384 patients (21%) had diabetes. The outcome measure was the composite of all-cause mortality, heart transplantation, and left ventricular assist device implantation after 10-year follow-up.RESULTSThe 10-year outcome in patients with diabetes was significantly worse than in those without diabetes (87% vs. 76%; adjusted hazard ratio [HR] 1.17 [95% CI 1.02–1.33]). Patients admitted in the last decade had a significantly lower 10-year event rate than patients admitted in the first two decades, both among patients without diabetes (adjusted HR 0.86 [95% CI 0.75–0.99]) and patients with diabetes (adjusted HR 0.80 [95% CI 0.63–1.00]).CONCLUSIONSThe long-term outcome of patients with diabetes is worse than that of patients without diabetes. However, the long-term prognosis improved over time in both groups. Importantly, this improvement in long-term prognosis was comparable in patients with and without diabetes. Despite these promising results, more awareness for diabetes in patients with acute HF is necessary and there is still need for optimal treatment of diabetes in acute HF.
      Keywords: Epidemiology-Cardiovascular Disease, Heart Failure
      PubDate: 2017-12-20T12:00:35-08:00
      DOI: 10.2337/dc17-0544
      Issue No: Vol. 41, No. 1 (2017)
  • The Prognostic Significance of Diabetes and Microvascular Complications in
           Patients With Heart Failure With Preserved Ejection Fraction
    • Authors: Sandesara; P. B.; ONeal, W. T.; Kelli, H. M.; Samman-Tahhan, A.; Hammadah, M.; Quyyumi, A. A.; Sperling, L. S.
      Pages: 150 - 155
      Abstract: OBJECTIVEThis study examined the prognostic significance of diabetes and microvascular complications in patients with heart failure with preserved ejection fraction (HFpEF).RESEARCH DESIGN AND METHODSThis analysis included 3,385 patients (mean age 69 ± 9.6 years; 49% male; 89% white) with HFpEF from the Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist Trial (TOPCAT). Diabetes and microvascular complications were ascertained by self-reported history and medical record review. Microvascular complications included neuropathy, nephropathy, and retinopathy. Outcomes included hospitalization, hospitalization for heart failure, death, and cardiovascular death. Cox regression was used to examine the risk of each outcome associated with diabetes and microvascular complications.RESULTSOf the 1,109 subjects (32%) with diabetes, 352 (32%) had at least one microvascular complication. Patients with diabetes and microvascular complications had an increased risk for hospitalization (no diabetes: referent; diabetes + no microvascular complication: hazard ratio [HR] 1.18, 95% CI 1.01, 1.37; diabetes + microvascular complications: HR 1.54, 95% CI 1.25, 1.89; P-trend
      Keywords: Epidemiology-Cardiovascular Disease, Heart Failure
      PubDate: 2017-12-20T12:00:35-08:00
      DOI: 10.2337/dc17-0755
      Issue No: Vol. 41, No. 1 (2017)
  • Cardiovascular Complications Over 5 Years and Their Association With
           Survival in the GERODIAB Cohort of Elderly French Patients With Type 2
    • Authors: Bauduceau; B.; Le Floch, J.-P.; Halimi, S.; Verny, C.; Doucet, J.; the SFD/SFGG Intergroup
      Pages: 156 - 162
      Abstract: OBJECTIVEThe GERODIAB study is a multicenter prospective observational study performed over 5 years in French patients aged 70 years or above with type 2 diabetes. This report deals with their cardiovascular complications and their relationship with survival.RESEARCH DESIGN AND METHODSConsecutive patients (n = 987, median age = 77 years) were included from 56 diabetes centers over 1 year. Individual characteristics, history and complications of diabetes, geriatric factors, and clinical and biological parameters were recorded. Survival was analyzed using the Kaplan-Meier method and proportional hazards regression models.RESULTSThe frequency of cardiovascular complications increased from 47% at inclusion to 67% at 5 years. The most frequent complications were coronary heart disease (increasing from 30% to 41%) and vascular disease of the lower limbs (25% to 35%) and of the cerebral vessels (15% to 26%). Heart failure was less common, but its frequency doubled during the follow-up (9% to 20%). It was strongly associated with poor survival (P < 0.0001), as was vascular disease of the lower limbs (P = 0.0004), whereas coronary heart disease (P = 0.0056) and vascular disease of cerebral vessels (P = 0.026) had mild associations. Amputation (P < 0.0001) and foot wounds (P < 0.0001) were strongly associated with survival. In multivariate models, heart failure was the strongest predictor of poor survival (hazard ratio [HR] 1.96 [95% CI 1.45–2.64]; P < 0.0001). It remained significant when other factors were considered simultaneously (HR 1.92 [95% CI 1.43–2.58]; P < 0.0001).CONCLUSIONSCardiovascular complications are associated with poor survival in elderly patients with type 2 diabetes, especially heart failure.
      Keywords: Complications-Macrovascular-Atherosclerotic Cardiovascular Disease and Human Diabetes, Heart Failure
      PubDate: 2017-12-20T12:00:35-08:00
      DOI: 10.2337/dc17-1437
      Issue No: Vol. 41, No. 1 (2017)
  • Changes in Albuminuria and the Risk of Major Clinical Outcomes in
           Diabetes: Results From ADVANCE-ON
    • Authors: Jun; M.; Ohkuma, T.; Zoungas, S.; Colagiuri, S.; Mancia, G.; Marre, M.; Matthews, D.; Poulter, N.; Williams, B.; Rodgers, A.; Perkovic, V.; Chalmers, J.; Woodward, M.; on behalf of the ADVANCE Collaborative Group
      Pages: 163 - 170
      Abstract: OBJECTIVETo assess the association between 2-year changes in urine albumin–to–creatinine ratio (UACR) and the risk of clinical outcomes in type 2 diabetes.RESEARCH DESIGN AND METHODSWe analyzed data from 8,766 participants in the Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation Post-Trial Observational Study (ADVANCE-ON). Change in UACR was calculated from UACR measurements 2 years apart, classified into three groups: decrease in UACR of ≥30%, minor change, and increase in UACR of ≥30%. By analyzing changes from baseline UACR groups, categorized into thirds, we repeated these analyses accounting for regression to the mean (RtM). The primary outcome was the composite of major macrovascular events, renal events, and all-cause mortality; secondary outcomes were these components. Cox regression models were used to estimate hazard ratios (HRs).RESULTSOver a median follow-up of 7.7 years, 2,191 primary outcomes were observed. Increases in UACR over 2 years independently predicted a greater risk of the primary outcome (HR for ≥30% UACR increase vs. minor change: 1.26; 95% CI 1.13–1.41), whereas a decrease in UACR was not significantly associated with lower risk (HR 0.93; 95% CI 0.83–1.04). However, after allowing for RtM, the effect of "real" decrease in UACR on the primary outcome was found to be significant (HR 0.84; 95% CI 0.75–0.94), whereas the estimated effect on an increase was unchanged.CONCLUSIONSChanges in UACR predicted changes in the risk of major clinical outcomes and mortality in type 2 diabetes, supporting the prognostic utility of monitoring albuminuria change over time.
      Keywords: Epidemiology-Cardiovascular Disease
      PubDate: 2017-12-20T12:00:35-08:00
      DOI: 10.2337/dc17-1467
      Issue No: Vol. 41, No. 1 (2017)
  • Enhanced Predictive Capability of a 1-Hour Oral Glucose Tolerance Test: A
           Prospective Population-Based Cohort Study
    • Authors: Pareek; M.; Bhatt, D. L.; Nielsen, M. L.; Jagannathan, R.; Eriksson, K.-F.; Nilsson, P. M.; Bergman, M.; Olsen, M. H.
      Pages: 171 - 177
      Abstract: OBJECTIVETo examine whether the 1-h blood glucose measurement would be a more suitable screening tool for assessing the risk of diabetes and its complications than the 2-h measurement.RESEARCH DESIGN AND METHODSWe conducted a prospective population-based cohort study of 4,867 men, randomly selected from prespecified birth cohorts between 1921 and 1949, who underwent an oral glucose tolerance test with blood glucose measurements at 0, 1, and 2 h. Subjects were followed for up to 39 years, with registry-based recording of events. Discriminative abilities of elevated 1-h (≥8.6 mmol/L) versus 2-h (≥7.8 mmol/L) glucose for predicting incident type 2 diabetes, vascular complications, and mortality were compared using Kaplan-Meier analysis, Cox proportional hazards regression, and net reclassification improvement.RESULTSMedian age was 48 years (interquartile range [IQR] 48–49). During follow-up (median 33 years [IQR 24–37]), 636 (13%) developed type 2 diabetes. Elevated 1-h glucose was associated with incident diabetes (hazard ratio 3.40 [95% CI 2.90–3.98], P < 0.001) and provided better risk assessment than impaired glucose tolerance (Harrell concordance index 0.637 vs. 0.511, P < 0.001). Addition of a 1-h measurement in subjects stratified by fasting glucose provided greater net reclassification improvement than the addition of a 2-h measurement (0.214 vs. 0.016, respectively). Finally, the 1-h glucose was significantly associated with vascular complications and mortality.CONCLUSIONSThe 1-h blood glucose level is a stronger predictor of future type 2 diabetes than the 2-h level and is associated with diabetes complications and mortality.
      Keywords: Epidemiology-Clinical-Diagnosis and Screening
      PubDate: 2017-12-20T12:00:35-08:00
      DOI: 10.2337/dc17-1351
      Issue No: Vol. 41, No. 1 (2017)
  • FGF23 Concentration and APOL1 Genotype Are Novel Predictors of Mortality
           in African Americans With Type 2 Diabetes
    • Authors: Chan; G. C.; Divers, J.; Russell, G. B.; Langefeld, C. D.; Wagenknecht, L. E.; Hsu, F.-C.; Xu, J.; Smith, S. C.; Palmer, N. D.; Hicks, P. J.; Bowden, D. W.; Register, T. C.; Ma, L.; Carr, J. J.; Freedman, B. I.
      Pages: 178 - 186
      Abstract: OBJECTIVECardiovascular and renal complications contribute to higher mortality in patients with diabetes. We assessed novel and conventional predictors of mortality in African American–Diabetes Heart Study (AA-DHS) participants.RESEARCH DESIGN AND METHODSAssociations between mortality and subclinical atherosclerosis, urine albumin–to–creatinine ratio (UACR), estimated glomerular filtration rate (eGFR), plasma fibroblast growth factor 23 (FGF23) concentration, African ancestry proportion, and apolipoprotein L1 genotypes (APOL1) were assessed in 513 African Americans with type 2 diabetes; analyses were performed using Cox proportional hazards models.RESULTSAt baseline, participants were 55.6% female with median (25th, 75th percentile) age 55 years (49.0, 62.0), diabetes duration 8 years (5.0, 13.0), glycosylated hemoglobin 60.7 mmol/mol (48.6, 76.0), eGFR 91.3 mL/min/1.73 m2 (76.4, 111.3), UACR 12.5 mg/mmol (4.2, 51.2), and coronary artery calcium 28.5 mg Ca2+ (1.0, 348.6); 11.5% had two APOL1 renal-risk variants. After 6.6-year follow-up (5.8, 7.5), 54 deaths were recorded. Higher levels of coronary artery calcified plaque, carotid artery calcified plaque, albuminuria, and FGF23 were associated with higher mortality after adjustment for age, sex, and African ancestry proportion. A penalized Cox regression that included all covariates and predictors associated with mortality identified male sex (hazard ratio [HR] 4.17 [95% CI 1.96–9.09]), higher FGF23 (HR 2.10 [95% CI 1.59–2.78]), and absence of APOL1 renal-risk genotypes (HR 0.07 [95% CI 0.01–0.69]) as the strongest predictors of mortality.CONCLUSIONSAccounting for conventional risk factors, higher FGF23 concentrations and APOL1 non–renal-risk genotypes associated with higher mortality in African Americans with diabetes. These data add to growing evidence supporting FGF23 association with mortality; mechanisms whereby these novel predictors impact survival remain to be determined.
      Keywords: Epidemiology-Other
      PubDate: 2017-12-20T12:00:35-08:00
      DOI: 10.2337/dc17-0820
      Issue No: Vol. 41, No. 1 (2017)
  • Clinical and Histologic Characterization of Nonalcoholic Steatohepatitis
           in African American Patients
    • Authors: Bril; F.; Portillo-Sanchez, P.; Liu, I.-C.; Kalavalapalli, S.; Dayton, K.; Cusi, K.
      Pages: 187 - 192
      Abstract: OBJECTIVEThere has been a widespread misconception among physicians that African Americans are protected from developing nonalcoholic steatohepatitis (NASH). However, a formal histologic and metabolic comparison against well-matched Caucasians has never been performed.RESEARCH DESIGN AND METHODSSixty-seven African American patients were matched 2:1 to Caucasians (n = 134) for age, sex, BMI, hemoglobin A1c, and prevalence of type 2 diabetes mellitus (T2DM). Screening for NASH included measurement of intrahepatic triglyceride content by proton MRS (1H-MRS), followed by a liver biopsy if patients had hepatic steatosis. Insulin resistance was estimated during an oral glucose tolerance test using the Matsuda Index.RESULTSCompared with Caucasians, African American patients had a lower intrahepatic triglyceride content (mean ± SD 6.1 ± 6.8% vs. 9.4 ± 7.5%, P = 0.007) and the presence of nonalcoholic fatty liver disease (NAFLD) was less common (25.0% vs. 51.9%, P = 0.003). However, prevalence of NASH was not different between ethnicities in patients with NAFLD (57.1% vs. 73.3%, P = 0.12). Moreover, they showed similar severity in each of the individual histologic parameters (inflammation, ballooning, and fibrosis). Among patients with NAFLD, insulin resistance was similar between both ethnic groups (Matsuda Index: 3.3 ± 1.8 vs. 3.1 ± 1.9, P = 0.61; adipose tissue insulin resistance [Adipo-IR] index: 5.7 ± 4.6 vs. 6.4 ± 4.7 mmol/L ⋅ µU/mL, P = 0.53) but appeared to be worse in African American versus Caucasian patients without NAFLD (Matsuda Index: 4.9 ± 3.6 vs. 7.0 ± 4.9, P = 0.11; Adipo-IR: 3.9 ± 2.8 vs. 2.7 ± 2.3 mmol/L ⋅ µU/mL, P = 0.06). African American patients also had lower plasma triglycerides and higher HDL cholesterol, independent of the severity of intrahepatic triglyceride.CONCLUSIONSAlthough African Americans have lower intrahepatic triglyceride accumulation, once NAFLD develops, NASH occurs as frequently, and as severe, as in Caucasian patients. Therefore, African Americans with NAFLD should be screened for NASH with the same degree of clinical resolve as in Caucasian patients.
      Keywords: Integrated Physiology-Liver
      PubDate: 2017-12-20T12:00:35-08:00
      DOI: 10.2337/dc17-1349
      Issue No: Vol. 41, No. 1 (2017)
  • Disparities in Environmental Exposures to Endocrine-Disrupting Chemicals
           and Diabetes Risk in Vulnerable Populations
    • Authors: Ruiz; D.; Becerra, M.; Jagai, J. S.; Ard, K.; Sargis, R. M.
      Pages: 193 - 205
      Abstract: Burgeoning epidemiological, animal, and cellular data link environmental endocrine-disrupting chemicals (EDCs) to metabolic dysfunction. Disproportionate exposure to diabetes-associated EDCs may be an underappreciated contributor to disparities in metabolic disease risk. The burden of diabetes is not uniformly borne by American society; rather, this disease disproportionately affects certain populations, including African Americans, Latinos, and low-income individuals. The purpose of this study was to review the evidence linking unequal exposures to EDCs with racial, ethnic, and socioeconomic diabetes disparities in the U.S.; discuss social forces promoting these disparities; and explore potential interventions. Articles examining the links between chemical exposures and metabolic disease were extracted from the U.S. National Library of Medicine for the period of 1966 to 3 December 2016. EDCs associated with diabetes in the literature were then searched for evidence of racial, ethnic, and socioeconomic exposure disparities. Among Latinos, African Americans, and low-income individuals, numerous studies have reported significantly higher exposures to diabetogenic EDCs, including polychlorinated biphenyls, organochlorine pesticides, multiple chemical constituents of air pollution, bisphenol A, and phthalates. This review reveals that unequal exposure to EDCs may be a novel contributor to diabetes disparities. Efforts to reduce the individual and societal burden of diabetes should include educating clinicians on environmental exposures that may increase disease risk, strategies to reduce those exposures, and social policies to address environmental inequality as a novel source of diabetes disparities.
      Keywords: Epidemiology-Other
      PubDate: 2017-12-20T12:00:35-08:00
      DOI: 10.2337/dc16-2765
      Issue No: Vol. 41, No. 1 (2017)
  • Issues and Events
    • Pages: 206 - 206
      PubDate: 2017-12-20T12:00:35-08:00
      DOI: 10.2337/dc18-ie01
      Issue No: Vol. 41, No. 1 (2017)
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