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Preview: Diabetes Care Journal publish ahead of print articles

Diabetes Care Journal publish ahead of print articles



Diabetes Care Journal publish ahead of print articles



 






Type 2 Diabetes in Relation to the Risk of Renal Cell Carcinoma Among Men and Women in Two Large Prospective Cohort Studies

2018-04-20T05:28:49-07:00

OBJECTIVE

We assessed whether type 2 diabetes is associated with renal cell carcinoma (RCC), independent of key potential confounders, in two large prospective cohorts with biennially updated covariate data.

RESEARCH DESIGN AND METHODS

A total of 117,570 women from the Nurses’ Health Study (NHS) and 48,866 men from the Health Professionals Follow-up Study (HPFS) were followed from 1976 and 1986, respectively, through 2014. Multivariable Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% CIs for associations between type 2 diabetes and pathology-confirmed RCC, overall and by stage, grade, and histological subtype.

RESULTS

During 38 years of follow-up in the NHS, we confirmed 418 RCC cases, including 120 fatal cases. Over 28 years in the HPFS, we confirmed 302 RCC cases, including 87 fatal cases. Women with type 2 diabetes had a significantly increased risk of RCC compared with women without type 2 diabetes (multivariable HR 1.53; 95% CI 1.14–2.04), with some evidence that the association was stronger for ≤5 (HR 2.15; 95% CI 1.44–3.23) than >5 (HR 1.22; 95% CI 0.84–1.78) years’ duration of type 2 diabetes (Pdifference 0.03). Among men, type 2 diabetes was not associated with total RCC (HR 0.89; 95% CI 0.56–1.41) or with RCC defined by stage, grade, or subtype. Sample sizes for analyses by stage, grade, and subtype were limited.

CONCLUSIONS

We found that type 2 diabetes was independently associated with a greater risk of RCC in women but not in men.




Hemoglobin A1c Accurately Predicts Continuous Glucose Monitoring-Derived Average Glucose in Youth and Young Adults With Cystic Fibrosis

2018-04-19T06:30:08-07:00

OBJECTIVE

In cystic fibrosis (CF), HbA1c is thought to underestimate glycemia. However, few studies have directly assessed the relationship between HbA1c and average glucose in CF. We determined the relationships among glycemic markers—HbA1c, fructosamine (FA), glycated albumin (%GA), and 1,5-anhydroglucitol (1,5-AG)—and continuous glucose monitoring (CGM) in CF, hypothesizing that alternate markers would better predict average sensor glucose (ASG) than HbA1c.

RESEARCH DESIGN AND METHODS

CF participants and a group of healthy control subjects (HC), ages 6–25 years, wore CGM for up to 7 days. Pearson correlations assessed the relationships between CGM variables and HbA1c, FA, %GA, and 1,5-AG. The regression line between HbA1c and ASG was compared in CF versus HC. Linear regressions determined whether alternate markers predicted ASG after adjustment for HbA1c.

RESULTS

CF (n = 93) and HC (n = 29) groups wore CGM for 5.2 ± 1 days. CF participants were 14 ± 3 years of age and 47% were male, with a BMI z score –0.1 ± 0.8 and no different from HCs in age, sex, or BMI. Mean HbA1c in CF was 5.7 ± 0.8% (39 ± 9 mmol/mol) vs. HC 5.1 ± 0.2% (32 ± 2 mmol/mol) (P < 0.0001). All glycemic markers correlated with ASG (P ≤ 0.01): HbA1c (r = 0.86), FA (r = 0.69), %GA (r = 0.83), and 1,5-AG (r = –0.26). The regression line between ASG and HbA1c did not differ in CF versus HC (P = 0.44). After adjustment for HbA1c, %GA continued to predict ASG (P = 0.0009) in CF.

CONCLUSIONS

HbA1c does not underestimate ASG in CF as previously assumed. No alternate glycemic marker correlated more strongly with ASG than HbA1c. %GA shows strong correlation with ASG and added to the prediction of ASG beyond HbA1c. However, we are not advocating use of HbA1c for diabetes screening in CF based on these results. Further study will determine whether glycemic measures other than ASG differ among different types of diabetes for a given HbA1c.




A Tailored Letter Based on Electronic Health Record Data Improves Gestational Weight Gain Among Women With Gestational Diabetes: The Gestational Diabetes Effects on Moms (GEM) Cluster-Randomized Controlled Trial

2018-04-18T06:45:05-07:00

OBJECTIVE

Evaluate whether a tailored letter improved gestational weight gain (GWG) and whether GWG mediated a multicomponent intervention’s effect on postpartum weight retention among women with gestational diabetes mellitus (GDM).

RESEARCH DESIGN AND METHODS

A cluster-randomized controlled trial of 44 medical facilities (n = 2,014 women) randomized to usual care or a multicomponent lifestyle intervention delivered during pregnancy (tailored letter) and postpartum (13 telephone sessions) to reduce postpartum weight retention. The tailored letter, using electronic health record (EHR) data, recommended an end-of-pregnancy weight goal tailored to prepregnancy BMI and GWG trajectory at GDM diagnosis: total GWG at the lower limit of the IOM range if BMI ≥18.5 kg/m2 or the midpoint if <18.5 kg/m2, and weight maintenance if women had exceeded this. The outcomes for this study were the proportion of women meeting the Institute of Medicine (IOM) guidelines for weekly rate of GWG from GDM diagnosis to delivery and meeting the end-of-pregnancy weight goal.

RESULTS

The tailored letter significantly increased the proportion of women meeting the IOM guidelines (72.6% vs. 67.1%; relative risk 1.08 [95% CI 1.01–1.17]); results were similar among women with BMI <25.0 kg/m2 (1.07 [1.00–1.15]) and ≥25.0 kg/m2 (1.08 [0.98–1.18]). Thirty-six percent in the intervention vs. 33.0% in usual care met the end-of-pregnancy weight goal (1.08 [0.99–1.18]); the difference was statistically significant among women with BMI <25.0 kg/m2 (1.28 [1.05–1.57]) but not ≥25.0 kg/m2 (0.99 [0.87–1.13]). Meeting the IOM guidelines mediated the effect of the multicomponent intervention in reducing postpartum weight retention by 24.6% (95% CI 11.3–37.8%).

CONCLUSIONS

A tailored EHR-based letter improved GWG, which mediated the effect of a multicomponent intervention in reducing postpartum weight retention.




Decreasing an Offloading Devices Size and Offsetting Its Imposed Limb Length Discrepancy Lead to Improved Comfort and Gait

2018-04-17T06:53:34-07:00

OBJECTIVE

Patient adherence is a challenge in offloading diabetic foot ulcers (DFUs) with removable cast walkers (RCWs). The size and weight of an RCW, changes to gait, and imposed limb length discrepancies may all discourage adherence. This study sought to determine whether RCW size and provision of a contralateral limb lift affected users’ comfort and gait.

RESEARCH DESIGN AND METHODS

Twenty-five individuals at risk for DFUs completed several 20-m walking trials under five footwear conditions: bilateral standardized shoes, a knee-high RCW with shoe with or without an external shoe lift contralaterally, and an ankle-high RCW with shoe with or without an external shoe lift contralaterally. Perceived comfort ratings were assessed through the use of visual analog scales. Spatial and temporal parameters of gait were captured by an instrumented walkway, and plantar pressure was measured and recorded using pedobarographic insoles.

RESULTS

The bilateral shoes condition was reported to be most comfortable; both RCW conditions without the lift were significantly less comfortable (P < 0.01). In contrast to the ankle-high RCW, the knee-high RCW resulted in significantly slower walking (5.6%; P < 0.01) but greater offloading in multiple forefoot regions of the offloaded foot (6.8–8.1%; P < 0.01). Use of the contralateral shoe lift resulted in significantly less variability in walking velocity (52.8%; P < 0.01) and reduced stance time for the offloaded foot (2.6%; P = 0.01), but it also reduced offloading in multiple forefoot regions of the offloaded foot (3.7–6.0%; P < 0.01).

CONCLUSIONS

Improved comfort and gait were associated with the ankle-high RCW and contralateral limb lift. Providing this combination to patients with active DFUs may increase offloading adherence and subsequently improve healing.




Association of Hemoglobin A1c and Wound Healing in Diabetic Foot Ulcers

2018-04-16T05:58:49-07:00

OBJECTIVE

This study evaluated the association between hemoglobin A1c (A1C) and wound outcomes in patients with diabetic foot ulcers (DFUs).

RESEARCH DESIGN AND METHODS

We conducted a retrospective analysis of an ongoing prospective, clinic-based study of patients with DFUs treated at an academic institution during a 4.7-year period. Data from 270 participants and 584 wounds were included in the analysis. Cox proportional hazards regression was used to assess the incidence of wound healing at any follow-up time in relation to categories of baseline A1C and the incidence of long-term (≥90 days) wound healing in relation to tertiles of nadir A1C change and mean A1C change from baseline, adjusted for potential confounders.

RESULTS

Baseline A1C was not associated with wound healing in univariate or fully adjusted models. Compared with a nadir A1C change from baseline of –0.29 to 0.0 (tertile 2), a nadir A1C change of 0.09 to 2.4 (tertile 3) was positively associated with long-term wound healing in the subset of participants with baseline A1C <7.5% (hazard ratio [HR], 2.07; 95% CI, 1.08–4.00), but no association with wound healing was seen with the mean A1C change from baseline in this group. Neither nadir A1C change nor mean A1C change were associated with long-term wound healing in participants with baseline A1C ≥7.5%.

CONCLUSIONS

There does not appear to be a clinically meaningful association between baseline or prospective A1C and wound healing in patients with DFUs. The paradoxical finding of accelerated wound healing and increase in A1C in participants with better baseline glycemic control requires confirmation in further studies.




Sustained Reduction in Severe Hypoglycemia in Adults With Type 1 Diabetes Complicated by Impaired Awareness of Hypoglycemia: 2-Year Follow-up in the HypoCOMPaSS Randomized Clinical Trial

2018-04-16T05:58:49-07:00

OBJECTIVE

Severe hypoglycemia is a feared complication of type 1 diabetes; yet, few trials have targeted prevention using optimized self-management (educational, therapeutic, and technological support). We aimed to investigate whether improved awareness and reduced severe hypoglycemia, achieved during an intensive randomized clinical trial (RCT), were sustained after return to routine care.

RESEARCH DESIGN AND METHODS

Ninety-six adults with type 1 diabetes (29 ± 12 years’ duration) and impaired awareness of hypoglycemia at five U.K. tertiary referral diabetes centers were recruited into a 24-week 2 x 2 factorial RCT (HypoCOMPaSS). Participants were randomized to pump (continuous subcutaneous insulin infusion [CSII]) or multiple daily injections (MDIs) and real-time continuous glucose monitoring (RT-CGM) or self-monitoring of blood glucose (SMBG), with equal education/attention to all groups. At 24 weeks, participants returned to routine care with follow-up until 24 months, including free choice of MDI/CSII; RT-CGM vs. SMBG comparison continued to 24 months. Primary outcome was mean difference (baseline to 24 months [between groups]) in hypoglycemia awareness.

RESULTS

Improvement in hypoglycemia awareness was sustained (Gold score at baseline 5.1 ± 1.1 vs. 24 months 3.7 ± 1.9; P < 0.0001). Severe hypoglycemia rate was reduced from 8.9 ± 12.8 episodes/person-year over the 12 months prestudy to 0.4 ± 0.8 over 24 months (P < 0.0001). HbA1c improved (baseline 8.2 ± 3.2% [66 ± 12 mmol/mol] vs. 24 months 7.7 ± 3.1% [61 ± 10 mmol/mol]; P = 0.003). Improvement in treatment satisfaction and reduced fear of hypoglycemia were sustained. There were no significant differences between interventions at 24 months.

CONCLUSIONS

Optimized insulin replacement and glucose monitoring underpinned by hypoglycemia-focused structured education should be provided to all with type 1 diabetes complicated by impaired awareness of hypoglycemia.




Neonatal Hypoglycemia Following Diet-Controlled and Insulin-Treated Gestational Diabetes Mellitus

2018-04-13T05:54:51-07:00

OBJECTIVE

To assess the risk of neonatal hypoglycemia following diet-controlled and insulin-treated gestational diabetes mellitus (GDM) and how it relates to birth weight.

RESEARCH DESIGN AND METHODS

Prospective cohort study including term neonates born after GDM from January 2013 through December 2015 at the University Medical Center Utrecht (Utrecht, the Netherlands). Routine screening of neonatal blood glucose levels was performed at 1, 3, 6, 12, and 24 h after birth. Main outcome measures were neonatal hypoglycemia defined as blood glucose ≤36 mg/dL (severe) and ≤47 mg/dL (mild).

RESULTS

A total of 506 neonates were included, born after pregnancies complicated by GDM treated either with insulin (22.5%) or without insulin (77.5%). The incidence of mild and severe hypoglycemia was similar in the insulin-treated and diet-controlled groups (33 vs. 35%, P = 0.66; and 20 vs. 21%, P = 0.79). A birth weight >90th centile was seen in 17.2% of all infants. Although children with a birth weight >90th centile had the highest risk for hypoglycemia, the vast majority of hypoglycemia (78.6%) was detected in those with a birth weight <90th centile. Over 95% of all hypoglycemia occurred within 12 h after birth.

CONCLUSIONS

Routine screening for neonatal hypoglycemia following pregnancies complicated by GDM reveals high incidence of both mild and severe hypoglycemia for both diet-controlled and insulin-treated GDM and across the full range of birth weight centiles. We propose routine blood glucose screening for neonatal hypoglycemia within the first 12 h of life in all neonates after GDM, irrespective of maternal insulin use or birth weight.




Exploring Variation in Glycemic Control Across and Within Eight High-Income Countries: A Cross-Sectional Analysis of 64,666 Children and Adolescents With Type 1 Diabetes

2018-04-12T06:45:10-07:00

OBJECTIVE

International studies on childhood type 1 diabetes (T1D) have focused on whole-country mean HbA1c levels, thereby concealing potential variations within countries. We aimed to explore the variations in HbA1c across and within eight high-income countries to best inform international benchmarking and policy recommendations.

RESEARCH DESIGN AND METHODS

Data were collected between 2013 and 2014 from 64,666 children with T1D who were <18 years of age across 528 centers in Germany, Austria, England, Wales, US, Sweden, Denmark, and Norway. We used fixed and random-effects models adjusted for age, sex, diabetes duration, and minority status to describe differences between center means and to calculate the proportion of total variation in HbA1c levels that is attributable to between-center differences (intraclass correlation [ICC]). We also explored the association between within-center variation and children’s glycemic control.

RESULTS

Sweden had the lowest mean HbA1c (59 mmol/mol [7.6%]) and together with Norway and Denmark showed the lowest between-center variations (ICC ≤ 4%). Germany and Austria had the next lowest mean HbA1c (61–62 mmol/mol [7.7–7.8%]) but showed the largest center variations (ICC ~15%). Centers in England, Wales, and the US showed low-to-moderate variation around high mean values. In pooled analysis, differences between counties remained significant after adjustment for children characteristics and center effects (P value <0.001). Across all countries, children attending centers with more variable glycemic results had higher HbA1c levels (5.6 mmol/mol [0.5%] per 5 mmol/mol [0.5%] increase in center HbA1c SD).

CONCLUSIONS

At similar average levels of HbA1c, countries display different levels of center variation. The distribution of glycemic achievement within countries should be considered in developing informed policies that drive quality improvement.




Cost-effectiveness of Continuous Glucose Monitoring for Adults With Type 1 Diabetes Compared With Self-Monitoring of Blood Glucose: the DIAMOND Randomized Trial

2018-04-12T06:45:10-07:00

OBJECTIVE

This study evaluated the societal cost-effectiveness of continuous glucose monitoring (CGM) in patients with type 1 diabetes (T1D) using multiple insulin injections.

RESEARCH DESIGN AND METHODS

In the Multiple Daily Injections and Continuous Glucose Monitoring in Diabetes (DIAMOND) trial, 158 patients with T1D and HbA1c ≥7.5% were randomized in a 2:1 ratio to CGM or control. Participants were surveyed at baseline and 6 months. Within-trial and lifetime cost-effectiveness analyses were conducted. A modified Sheffield T1D policy model was used to simulate T1D complications. The main outcome was cost per quality-adjusted life-year (QALY) gained.

RESULTS

Within the 6-month trial, the CGM group had similar QALYs to the control group (0.462 ± 0.05 vs. 0.455 ± 0.06 years, P = 0.61). The total 6-month costs were $11,032 (CGM) vs. $7,236 (control). The CGM group experienced reductions in HbA1c (0.60 ± 0.74% difference in difference [DiD]), P < 0.01), the daily rate of nonsevere hypoglycemia events (0.07 DiD, P = 0.013), and daily test strip use (0.55 ± 1.5 DiD, P = 0.04) compared with the control group. In the lifetime analysis, CGM was projected to reduce the risk of T1D complications and increase QALYs by 0.54. The incremental cost-effectiveness ratio (ICER) was $98,108 per QALY for the overall population. By extending sensor use from 7 to 10 days in a real-world scenario, the ICER was reduced to $33,459 per QALY.

CONCLUSIONS

For adults with T1D using multiple insulin injections and still experiencing suboptimal glycemic control, CGM is cost-effective at the willingness-to-pay threshold of $100,000 per QALY, with improved glucose control and reductions in nonsevere hypoglycemia.







Higher Collagen VI Formation Is Associated With All-Cause Mortality in Patients With Type 2 Diabetes and Microalbuminuria

2018-04-11T06:18:55-07:00

OBJECTIVE

Type 2 diabetes is a common risk factor for the development of chronic kidney disease (CKD). Enhanced de novo collagen type VI (COL VI) formation has been associated with renal fibrosis and CKD. We investigated the hypothesis that PRO-C6, a product specifically generated during COL VI formation, is prognostic for adverse outcomes in patients with type 2 diabetes and microalbuminuria.

RESEARCH DESIGN AND METHODS

In a prospective, observational study, we measured PRO-C6 in serum (S-PRO-C6) and urine (U-PRO-C6) of 198 patients with type 2 diabetes and microalbuminuria without symptoms of coronary artery disease. Patients were followed for a median of 6.5 years, and end points were a composite of cardiovascular events (n = 38), all-cause mortality (n = 26), and reduction of estimated glomerular filtration rate (eGFR) of >30% (disease progression [n = 42]). Cox models were unadjusted and adjusted for the conventional risk factors sex, age, BMI, systolic blood pressure, LDL cholesterol, smoking, HbA1c, plasma creatinine, and urinary albumin excretion rate.

RESULTS

Doubling of S-PRO-C6 increased hazards for cardiovascular events (hazard ratio 3.06 [95% CI 1.31–7.14]), all-cause mortality (6.91 [2.96–16.11]), and disease progression (4.81 [1.92–12.01]). Addition of S-PRO-C6 to a model containing conventional risk factors improved relative integrated discrimination by 22.5% for cardiovascular events (P = 0.02), 76.8% for all-cause mortality (P = 0.002), and 53.3% for disease progression (P = 0.004). U-PRO-C6 was not significantly associated with any of the outcomes.

CONCLUSIONS

S-PRO-C6 generated during COL VI formation predicts cardiovascular events, all-cause mortality, and disease progression in patients with type 2 diabetes and microalbuminuria.




Appetite, Glycemia, and Entero-Insular Hormone Responses Differ Between Oral, Gastric-Remnant, and Duodenal Administration of a Mixed-Meal Test After Roux-en-Y Gastric Bypass

2018-04-10T05:34:58-07:00

OBJECTIVE

To examine the effect of different feeding routes on appetite and metabolic responses after Roux-en-Y gastric bypass (RYGB).

RESEARCH DESIGN AND METHODS

A standard liquid meal was administered either orally, into the gastric remnant, or intraduodenally 6 months after RYGB. Changes in plasma glucose, insulin, glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), peptide-YY (PYY), and appetite were measured pre- and postprandially.

RESULTS

Postprandial GLP-1 and PYY responses were similar, whereas glucose, insulin, and GIP levels differed markedly after oral versus intraduodenal feeding. Intraduodenal feeding prompted an intermediate appetite response (i.e., between oral and intragastric). For postprandial glucose, insulin, and GIP levels, the intraduodenal route was more similar to the intragastric than oral route. Intragastric administration did not evoke changes in appetite, glucose, or insulin; however, it slightly increased GLP-1 and PYY and moderately increased GIP.

CONCLUSIONS

Appetite and metabolic responses after RYGB depend on the route by which nutrients enter the gastrointestinal tract.




Intensive Treat-to-Target Statin Therapy in High-Risk Japanese Patients With Hypercholesterolemia and Diabetic Retinopathy: Report of a Randomized Study

2018-04-06T05:41:52-07:00

OBJECTIVE

Diabetes is associated with high risk of cardiovascular (CV) events, particularly in patients with dyslipidemia and diabetic complications. We investigated the incidence of CV events with intensive or standard lipid-lowering therapy in patients with hypercholesterolemia, diabetic retinopathy, and no history of coronary artery disease (treat-to-target approach).

RESEARCH DESIGN AND METHODS

In this multicenter, prospective, randomized, open-label, blinded end point study, eligible patients were randomly assigned (1:1) to intensive statin therapy targeting LDL cholesterol (LDL-C) <70 mg/dL (n = 2,518) or standard statin therapy targeting LDL-C 100–120 mg/dL (n = 2,524).

RESULTS

Mean follow-up was 37 ± 13 months. LDL-C at 36 months was 76.5 ± 21.6 mg/dL in the intensive group and 104.1 ± 22.1 mg/dL in the standard group (P < 0.001). The primary end point events occurred in 129 intensive group patients and 153 standard group patients (hazard ratio [HR] 0.84 [95% CI 0.67–1.07]; P = 0.15). The relationship between the LDL-C difference in the two groups and the event reduction rate was consistent with primary prevention studies in patients with diabetes. Exploratory findings showed significantly fewer cerebral events in the intensive group (HR 0.52 [95% CI 0.31–0.88]; P = 0.01). Safety did not differ significantly between the two groups.

CONCLUSIONS

We found no significant decrease in CV events or CV-associated deaths with intensive therapy, possibly because our between-group difference of LDL-C was lower than expected (27.7 mg/dL at 36 months of treatment). The potential benefit of achieving LDL-C <70 mg/dL in a treat-to-target strategy in high-risk patients deserves further investigation.




Risk of Incident Heart Failure in Patients With Diabetes and Asymptomatic Left Ventricular Systolic Dysfunction

2018-04-06T05:41:52-07:00

OBJECTIVE

Although diabetes is well known to be common in prevalent heart failure (HF) and portends a poor prognosis, the role of diabetes in the development of incident HF is less well understood. We studied the role of diabetes in the transition from asymptomatic left ventricular systolic dysfunction (ALVSD) to overt HF in the prevention arm of the Studies of Left Ventricular Dysfunction (SOLVD-P).

RESEARCH DESIGN AND METHODS

We examined the development of symptomatic HF, HF hospitalization, and cardiovascular death according to diabetes status at baseline in patients in SOLVD-P. These outcomes were analyzed by using cumulative incidence curves and Cox regression models adjusted for age, sex, and other prognostic factors, including randomized treatment, HF severity, and comorbidity.

RESULTS

Of the 4,223 eligible participants, 647 (15%) had diabetes at baseline. Patients with diabetes were older and had a higher average weight, systolic blood pressure, and heart rate. During the median follow-up of 36 months, 861 of the 3,576 patients without diabetes (24%) developed HF compared with 214 of the 647 patients with diabetes (33%). In unadjusted analyses, patients with diabetes had a higher risk of development of HF (hazard ratio 1.53 [95% CI 1.32–1.78]; P < 0.001), HF hospitalization (2.04 [1.65–2.52]; P < 0.0001), and the composite outcome of development of HF or cardiovascular death (1.48 [1.30–1.69]; P < 0.001). The effect of enalapril on outcomes was not modified by diabetes status.

CONCLUSIONS

In patients with ALVSD, diabetes is associated with an increased risk of developing HF. Development of HF is associated with an increased risk of death irrespective of diabetes status.




Postoperative Death After Lower-Limb Amputation in a National Prevalent Cohort of Patients With Diabetes

2018-04-05T06:25:19-07:00

OBJECTIVE

The objectives of this study were to 1) describe postoperative mortality after lower-limb amputation in a national prevalent cohort of patients with diabetes, and 2) investigate whether postoperative mortality differs by demographic subgroup, patient morbidity level, and health system factors related to the facility in which the amputation occurred.

RESEARCH DESIGN AND METHODS

A national prevalent cohort of 302,339 individuals diagnosed with diabetes between 2005 and 2014 were followed until the end of 2014 for major and minor lower-limb amputation and subsequent postoperative mortality by using national health data collections. Kaplan-Meier survival analysis was used to determine postoperative survival, whereas Cox proportional hazards models were used to describe the relative hazard of postoperative mortality, adjusted for covariates.

RESULTS

A total of 6,352 lower-limb amputations occurred over the study period (2,570 major amputations, 3,782 minor amputations). More than 11% of patients who underwent major amputation died within 30 days, whereas nearly 18% died within 90 days. Death was most common among older patients and indigenous Māori. Sex, deprivation, rurality, hospital volume, admission type, and patient comorbidity were not consistently or substantially independently associated with risk of postoperative mortality.

CONCLUSIONS

In a national prevalent cohort of patients with diabetes, there was high risk of postoperative mortality as well as a differential risk of postoperative mortality by demographic subgroup. Further work is required to investigate the drivers of postoperative mortality among patients with diabetes who undergo amputation.




One-Hour Plasma Glucose Compared With 2-Hour Plasma Glucose in Relation to Diabetic Retinopathy in American Indians

2018-04-05T06:25:18-07:00

OBJECTIVE

We compared the ability of 1- and 2-h plasma glucose concentrations (1h-PG and 2h-PG, respectively), derived from a 75-g oral glucose tolerance test (OGTT), to predict retinopathy. 1h-PG and 2h-PG concentrations, measured in a longitudinal study of an American Indian community in the southwestern U.S., a population at high risk for type 2 diabetes, were analyzed to assess the usefulness of the 1h-PG to identify risk of diabetic retinopathy (DR).

RESEARCH DESIGN AND METHODS

Cross-sectional (n = 2,895) and longitudinal (n = 1,703) cohorts were assessed for the prevalence and incidence of DR, respectively, in relation to deciles of 1h-PG and 2h-PG concentrations. Areas under the receiver operating characteristic (ROC) curves for 1h-PG and 2h-PG were compared with regard to predicting DR, as assessed by direct ophthalmoscopy.

RESULTS

Prevalence and incidence of DR, based on direct ophthalmoscopy, changed in a similar manner across the distributions of 1h-PG and 2h-PG concentrations. ROC analysis showed that 1h-PG and 2h-PG were of similar value in identifying prevalent and incident DR using direct ophthalmoscopy. 1h-PG cut points of 230 and 173 mg/dL were comparable to 2h-PG cut points of 200 mg/dL (type 2 diabetes) and 140 mg/dL (impaired glucose tolerance), respectively.

CONCLUSIONS

1h-PG is a useful predictor of retinopathy risk, has a predictive value similar to that of 2h-PG, and may be considered as an alternative glucose time point during an OGTT.




The Risk of Acute Pancreatitis After Initiation of Dipeptidyl Peptidase 4 Inhibitors: Testing a Hypothesis of Subgroup Differences in Older U.S. Adults

2018-04-04T07:43:53-07:00

OBJECTIVE

To examine whether dipeptidyl peptidase 4 inhibitors (DPP-4I) increase acute pancreatitis risk in older patients and whether the association varies by age, sex, and history of cardiovascular disease (CVD).

RESEARCH DESIGN AND METHODS

We conducted a cohort study of DPP-4I initiators versus thiazolidinedione (TZD) or sulfonylurea initiators using U.S. Medicare beneficiaries, 2007–2014. Eligible initiators were aged 66+ years without history of pancreatic disease or alcohol-related diseases. Patients were followed up for hospitalization due to acute pancreatitis and censored at 90 days after treatment changes. Weighted Cox models were used to estimate the hazard ratio (HR) for acute pancreatitis. Analyses were performed overall as well as within subgroups defined by age, sex, and CVD history.

RESULTS

We found no increased risk of acute pancreatitis comparing 49,374 DPP-4I initiators to 132,223 sulfonylurea initiators (weighted HR 1.01; 95% CI 0.83–1.24) and comparing 57,301 DPP-4I initiators to 32,612 TZD initiators (weighted HR 1.11; 95% CI 0.76–1.62). Age and sex did not modify the association. Among patients with CVD, acute pancreatitis incidence was elevated in initiators of DPP-4I and sulfonylurea (2.3 and 2.4 per 1,000 person-years, respectively) but not in TZD initiators (1.5). Among patients with CVD, higher risk of acute pancreatitis was observed with DPP-4I compared with TZD (weighted HR 1.84; 95% CI 1.02–3.35) but not compared with sulfonylurea.

CONCLUSIONS

Our study provides evidence that DPP-4I is not associated with an increased risk of acute pancreatitis in older adults overall. The positive association observed in patients with CVD could be due to chance or bias but merits further investigation.




Influence of Diabetes on Trends in Perioperative Cardiovascular Events

2018-04-04T07:43:53-07:00

OBJECTIVE

Patients undergoing noncardiac surgery frequently have diabetes mellitus (DM) and an elevated risk of cardiovascular disease. It is unknown whether temporal declines in the frequency of perioperative major adverse cardiovascular and cerebrovascular events (MACCEs) apply to patients with DM.

RESEARCH DESIGN AND METHODS

Patients ≥45 years of age who underwent noncardiac surgery from January 2004 to December 2013 were identified using the U.S. National Inpatient Sample. DM was identified using ICD-9 diagnosis codes. Perioperative MACCEs (in-hospital all-cause mortality, acute myocardial infarction, or acute ischemic stroke) by DM status were evaluated over time.

RESULTS

The final study sample consisted of 10,581,621 hospitalizations for major noncardiac surgery; DM was present in ~23% of surgeries and increased over time (P for trend <0.001). Patients with DM experienced MACCEs in 3.3% of surgeries vs. 2.8% of surgeries for patients without DM (P < 0.001). From 2004 to 2013, the odds of perioperative MACCEs after multivariable adjustment increased by 6% (95% CI 2–9%) for DM patients, compared with an 8% decrease (95% CI –10% to –6%) for patients without DM (P for interaction <0.001). Trends for individual end points were all less favorable for patients with DM versus those without DM.

CONCLUSIONS

In an analysis of >10.5 million noncardiac surgeries from a large U.S. hospital admission database, perioperative MACCEs were more common among patients with DM versus without DM. Perioperative MACCEs increased over time and individual end points were all less favorable for patients with DM. Our findings suggest that a substantial unmet need exists for strategies to reduce the risk of perioperative cardiovascular events among patients with DM.







AGE Content of a Protein Load Is Responsible for Renal Performances: A Pilot Study

2018-04-02T06:47:16-07:00

OBJECTIVE

Chronic kidney disease is associated with higher morbidity and mortality in patients with diabetes. A low-protein diet is recommended to slow diabetic nephropathy progression because each protein load leads to renal hemodynamic variations. The aim of our study was to evaluate whether the advanced glycation end products (AGE) content of a protein load is responsible for the protein-induced renal hemodynamic variations in humans.

RESEARCH DESIGN AND METHODS

Ten healthy subjects were assigned to a high-protein (1 g/kg) low-AGE (3,000 kU AGE) versus high-AGE (30,000 kU AGE) meal. Renal perfusion, oxygen consumption, and oxygen content were measured before and 120 min after each meal.

RESULTS

Renal perfusion (3.2 ± 0.5 vs. 3.8 ± 0.4 mL/min/g (P = 0.0002) and oxygen consumption (0.3 ± 0.04 vs 0.4 ± 0.08 min–1, P = 0.005) increased significantly after the high-AGE meal compared with the low-AGE meal.

CONCLUSIONS

Our results suggest that the AGE content of a protein load is responsible for renal hemodynamic modifications. Therefore, prevention of diabetic nephropathy progression could aim predominantly at reducing food AGE content.




Specific Hepatic Sphingolipids Relate to Insulin Resistance, Oxidative Stress, and Inflammation in Nonalcoholic Steatohepatitis

2018-03-30T05:49:53-07:00

OBJECTIVE

Insulin resistance and nonalcoholic fatty liver (NAFL) disease have been linked to several lipid metabolites in animals, but their role in humans remains unclear. This study examined the relationship of sphingolipids with hepatic and peripheral metabolism in 21 insulin-resistant obese patients without (NAFL–) or with (NAFL+) and nonalcoholic steatohepatitis (NASH), and 7 healthy lean individuals undergoing tissue biopsies during bariatric or elective abdominal surgery.

RESEARCH DESIGN AND METHODS

Hyperinsulinemic-euglycemic clamps with d-[6,6-2H2]glucose were performed to quantify tissue-specific insulin sensitivity. Hepatic oxidative capacity, lipid peroxidation, and the phosphorylated-to-total c-Jun N-terminal kinase (pJNK-to-tJNK) ratio was measured to assess mitochondrial function, oxidative stress, and inflammatory activity.

RESULTS

Hepatic total ceramides were higher by 50% and 33% in NASH compared with NAFL+ and NAFL–, respectively. Only in NASH were hepatic dihydroceramides (16:0, 22:0, and 24:1) and lactosylceramides increased. Serum total ceramides and dihydroceramides (hepatic dihydroceramides 22:0 and 24:1) correlated negatively with whole-body but not with hepatic insulin sensitivity. Hepatic maximal respiration related positively to serum lactosylceramides subspecies, hepatic sphinganine, and lactosylceramide 14:0. Liver lipid peroxides (total ceramides, sphingomyelin 22:0) and the pJNK-to-tJNK ratio (ceramide 24:0; hexosylceramides 22:0, 24:0, and 24:1) all positively correlated with the respective hepatic sphingolipids.

CONCLUSIONS

Sphingolipid species are not only increased in insulin-resistant humans with NASH but also correlate with hepatic oxidative stress and inflammation, suggesting that these lipids may play a role during progression of simple steatosis to NASH in humans.




Effects of Smoking Versus Nonsmoking on Postprandial Glucose Metabolism in Heavy Smokers Compared With Nonsmokers

2018-03-30T05:49:53-07:00

OBJECTIVE

Epidemiological studies suggest that smoking increases the risk of type 2 diabetes. We hypothesized that smoking-derived nicotine and ensuing activation of nicotinic cholinergic receptors in the gastrointestinal tract and the autonomic nervous system would have a detrimental effect on postprandial glucose metabolism and, thus, potentially constitute a link between smoking and the development of type 2 diabetes.

RESEARCH DESIGN AND METHODS

We subjected 11 male heavy smokers to two identical 4-h liquid mixed-meal tests: one with concomitant cigarette smoking (immediately before and after meal intake) and one without smoking. Twelve age-, sex-, and BMI-matched nonsmokers underwent an identical meal test without smoking.

RESULTS

The smokers were characterized by higher fasting plasma concentrations of glucagon compared with the nonsmokers. Among smokers, cigarette smoking before and after the meal significantly reduced postprandial plasma glucose excursions. There were no differences in gut or pancreatic hormone concentrations between the test days in the smoking group, and the responses were similar to those in the control group.

CONCLUSIONS

Our results suggest that smoking in association with meal intake decreases the postprandial plasma glucose concentrations, possibly through decreased gastric emptying, and that elevated fasting glucagon concentrations rather than smoking-induced alterations in postprandial glucose and hormone responses may be associated with the elevated risk of type 2 diabetes in chronic smokers.




Relationship Between Metabolic Syndrome, Alanine Aminotransferase Levels, and Liver Disease Severity in a Multiethnic North American Cohort With Chronic Hepatitis B

2018-03-29T06:39:43-07:00

OBJECTIVE

Metabolic syndrome (MS) is prevalent and is associated with adverse outcomes of liver disease. We evaluated the prevalence of MS and its influence on alanine aminotransferase (ALT) levels and fibrosis, as estimated by the aspartate aminotransferase–to–platelet ratio index (APRI), in a large, multiethnic North American cohort with chronic hepatitis B (HBV) infection.

RESEARCH DESIGN AND METHODS

Adults with chronic HBV from 21 centers within the U.S. and Canada were evaluated at baseline and for up to 5 years (median 3.7 years) of follow-up. MS was defined as the presence of at least three of five criteria including waist circumference, blood pressure, glucose, triglyceride, and HDL levels.

RESULTS

Analysis included 777 participants, of whom 171 (22%) had MS. Participants with MS (vs. those without MS) were older (median age 54.4 vs. 40.2 years), more often male (61% vs. 51%), and born in the U.S./Canada or had immigrated >20 years ago (60% vs. 43%). MS was not associated with ALT or APRI at baseline. Upon adjusted multivariable analysis of serial ALT values, ALT was significantly higher (mean 12%; P = 0.02) among those with MS at baseline and even higher (mean 19%; P = 0.003) among those with persistent MS compared with those with persistent absence of MS. MS was not associated with serial APRI on follow-up.

CONCLUSIONS

MS was prevalent in this HBV cohort and was independently associated with higher ALT levels longitudinally. These findings highlight the importance of screening for MS and the potential for MS to influence ALT and its interpretation in the context of HBV treatment decisions.




Diabetes Distress and Glycemic Control: The Buffering Effect of Autonomy Support From Important Family Members and Friends

2018-03-29T06:39:43-07:00

OBJECTIVE

To examine whether autonomy support (defined as social support for an individual’s personal agency) for diabetes management from informal health supporters (family/friends) reduces the detrimental effects of diabetes distress on glycemic control.

RESEARCH DESIGN AND METHODS

Three hundred eight veterans with type 2 diabetes and one or more risk factors for diabetes complications completed a survey that included measures of diabetes distress and perceived autonomy support from their main informal health supporter. Hemoglobin A1c (HbA1c) data from 12 months before and after the survey were extracted from electronic medical records. Linear mixed modeling examined the main effects and interaction of autonomy support and diabetes distress on repeated measures of HbA1c over the 12 months after the survey, controlling for mean prior 12-month HbA1c, time, insulin use, age, and race/ethnicity.

RESULTS

Diabetes distress (B = 0.12 [SE 0.05]; P = 0.023) was associated with higher and autonomy support (B = –0.16 [SE 0.07]; P = 0.032), with lower subsequent HbA1c levels. Autonomy support moderated the relationship between diabetes distress and HbA1c (B = –0.13 [SE 0.06]; P = 0.027). Greater diabetes distress was associated with higher HbA1c at low (B = 0.21 [SE 07]; P = 0.002) but not high (B = 0.01 [SE 0.07]; P = 0.890) autonomy support.

CONCLUSIONS

Autonomy support from main health supporters may contribute to better glycemic control by ameliorating the effects of diabetes distress. Interventions that reduce diabetes distress and enhance the autonomy supportiveness of informal supporters may be effective approaches to improving glycemic control.




Effect of Achieved Systolic Blood Pressure on Cardiovascular Outcomes in Patients With Type 2 Diabetes Mellitus: A Population-Based Retrospective Cohort Study

2018-03-28T06:12:02-07:00

OBJECTIVE

The objective of this study was to compare the incidence of cardiovascular disease (CVD) among patients with type 2 diabetes mellitus (T2DM) with treated hypertension who achieved systolic blood pressures (SBPs) of <120, <130, and <140 mmHg after an increase in their antihypertensive regimen.

RESEARCH DESIGN AND METHODS

A retrospective cohort study was conducted on 28,014 primary care adult patients with T2DM with no prior diagnosis of CVD and who achieved SBP readings <140 mmHg after an increase in the number of antihypertensive medications prescribed. Using an extension of propensity score matching, a total of 2,079, 10,851, and 15,084 matched patients with achieved SBP measurements of <120, <130, and <140 mmHg were identified. The association between achieved SBP and incident CVD were evaluated using Cox regressions. Subgroup analyses were conducted by stratifying patients’ baseline characteristics.

RESULTS

Over a median follow-up period of 4.8 years, the incidence of CVD in patients with achieved SBP measures of <120, <130, and <140 mmHg were 318 (15.3%; incidence rate [IR] 34.3/1,000 person-years [PY]), 992 (9.1%; IR 20.4/1,000 PY), and 1,635 (10.8%; IR 21.4/1,000 PY). Achieved SBP <120 mmHg was associated with a higher risk of CVD compared with achieved SBP <130 mmHg (hazard ratio [HR] 1.75 [95% CI 1.53, 2.00]) and achieved SBP <140 mmHg (HR 1.67 [95% CI 1.46, 1.90]). There was a significant reduction in CVD risk in patients <65 years (HR 0.81 [95% CI 0.69, 0.96]) but no difference for other patients, including patients ≥65 years, who achieved SBP <130 mmHg when compared with the group that achieved SBP <140 mmHg.

CONCLUSIONS

Our findings support a SBP treatment target of 140 mmHg and suspect no risk reduction attenuation on CVD for lower SBP targets (<120 or <130 mmHg) for most patients with uncomplicated T2DM. A randomized control trial is still needed to confirm these findings.




Associations Between Changes in Depressive Symptoms and Social Support and Diabetes Management Among Low-Income, Predominantly Hispanic Patients in Patient-Centered Care

2018-03-27T06:22:29-07:00

OBJECTIVE

This study examined whether changes in depressive symptoms and social support prospectively predicted diabetes management among Hispanic patients with probable depression in patient-centered medical homes at safety-net clinics in East Los Angeles, CA.

RESEARCH DESIGN AND METHODS

Data were collected from 251 patients enrolled in a randomized clinical trial testing the effectiveness of a promotora-assisted self-management intervention. Cross-lagged analyses examined associations between changes in depression symptoms and social support between baseline and 6-month follow-up and self-efficacy and adherence to diabetes management at the 6- and 12-month follow-ups.

RESULTS

Changes in depressive symptoms predicted self-efficacy and level of adherence at the 6- and 12-month follow-ups. Changes in total social support and emotional social support were correlated only with self-efficacy regarding diabetes management at 6-month follow-up.

CONCLUSIONS

Decline in depressive symptoms is a reliable predictor of improvement in self-efficacy and adherence to diabetes management. Further studies are recommended to study psychosocial mechanisms related to social relationships other than social support that affect diabetes management.




The Presence of Diabetes and Higher HbA1c Are Independently Associated With Adverse Outcomes After Surgery

2018-03-26T11:45:14-07:00

OBJECTIVE

Limited studies have examined the association between diabetes and HbA1c with postoperative outcomes. We investigated the association of diabetes, defined categorically and HbA1c as a continuous measure, with postoperative outcomes.

RESEARCH DESIGN AND METHODS

In this prospective, observational study, we measured the HbA1c of surgical inpatients age ≥54 years at a tertiary hospital between May 2013 and January 2016. Patients were diagnosed with diabetes if they had preexisting diabetes or an HbA1c ≥6.5% (48 mmol/mol) or with prediabetes if they had an HbA1c between 5.7–6.4% (39–48 mmol/mol). Patients with an HbA1c <5.7% (39 mmol/mol) were categorized as having normoglycemia. Baseline demographic and clinical data were obtained from hospital records, and patients were followed for 6 months. Random-effects logistic and negative binomial regression models were used for analysis, treating surgical units as random effects. We undertook classification and regression tree (CART) analysis to design a 6-month mortality risk model.

RESULTS

Of 7,565 inpatients, 30% had diabetes, and 37% had prediabetes. After adjusting for age, Charlson comorbidity index (excluding diabetes and age), estimated glomerular filtration rate, and length of surgery, diabetes was associated with increased 6-month mortality (adjusted odds ratio [aOR] 1.29 [95% CI 1.05–1.58]; P = 0.014), major complications (1.32 [1.14–1.52]; P < 0.001), intensive care unit (ICU) admission (1.50 [1.28–1.75]; P < 0.001), mechanical ventilation (1.67 [1.32–2.10]; P < 0.001), and hospital length of stay (LOS) (adjusted incidence rate ratio [aIRR] 1.08 [95% CI 1.04–1.12]; P < 0.001). Each percentage increase in HbA1c was associated with increased major complications (aOR 1.07 [1.01–1.14]; P = 0.030), ICU admission (aOR 1.14 [1.07–1.21]; P < 0.001), and hospital LOS (aIRR 1.05 [1.03–1.06]; P < 0.001). CART analysis confirmed a higher risk of 6-month mortality with diabetes in conjunction with other risk factors.

CONCLUSIONS

Almost one-third of surgical inpatients age ≥54 years had diabetes. Diabetes and higher HbA1c were independently associated with a higher risk of adverse outcomes after surgery.




Gestational Diabetes Mellitus: Does One Size Fit All? A Challenge to Uniform Worldwide Diagnostic Thresholds

2018-03-20T07:15:40-07:00

OBJECTIVE

To define the prevalence and pregnancy outcomes related to elevated fasting venous plasma glucose (FVPG) in a Danish pregnancy cohort.

RESEARCH DESIGN AND METHODS

This was an observational cohort study including 1,516 women without gestational diabetes mellitus (GDM) by Danish criteria. FVPG measured at 28 weeks’ gestation was related to pregnancy outcomes.

RESULTS

With use of the World Health Organization 2013 threshold of FVPG ≥5.1 mmol/L, 40.1% of the cohort qualified as having GDM. There was no evidence of excess fetal growth, hypertension in pregnancy, or caesarean delivery in women with FVPG <5.6 mmol/L.

CONCLUSIONS

The WHO 2013 FVPG threshold for GDM is unsuitable for Denmark. It inappropriately labels as having GDM an unmanageably large number of women who are at low absolute risk of pregnancy complications.




Food Insecurity, Food "Deserts," and Glycemic Control in Patients With Diabetes: A Longitudinal Analysis

2018-03-19T06:45:54-07:00

OBJECTIVE

Both food insecurity (limited food access owing to cost) and living in areas with low physical access to nutritious foods are public health concerns, but their relative contribution to diabetes management is poorly understood.

RESEARCH DESIGN AND METHODS

This was a prospective cohort study. A random sample of patients with diabetes in a primary care network completed food insecurity assessment in 2013. Low physical food access at the census tract level was defined as no supermarket within 1 mile in urban areas and 10 miles in rural areas. HbA1c measurements were obtained from electronic health records through November 2016. The relationship among food insecurity, low physical food access, and glycemic control (as defined by HbA1c) was analyzed using hierarchical linear mixed models.

RESULTS

Three hundred and ninety-one participants were followed for a mean of 37 months. Twenty percent of respondents reported food insecurity, and 31% resided in an area of low physical food access. In adjusted models, food insecurity was associated with higher HbA1c (difference of 0.6% [6.6 mmol/mol], 95% CI 0.4–0.8 [4.4–8.7], P < 0.0001), which did not improve over time (P = 0.50). Living in an area with low physical food access was not associated with a difference in HbA1c (difference 0.2% [2.2 mmol/mol], 95% CI –0.2 to 0.5 [–2.2 to 5.6], P = 0.33) or with change over time (P = 0.07).

CONCLUSIONS

Food insecurity is associated with higher HbA1c, but living in an area with low physical food access is not. Food insecurity screening and interventions may help improve glycemic control for vulnerable patients.




Patient Characteristics Associated With Severe Hypoglycemia in a Type 2 Diabetes Cohort in a Large, Integrated Health Care System From 2006 to 2015

2018-03-16T06:28:38-07:00

OBJECTIVE

To identify severe hypoglycemia events, defined as emergency department visits or hospitalizations for hypoglycemia, in patients with type 2 diabetes receiving care in a large health system and to identify patient characteristics associated with severe hypoglycemia events.

RESEARCH DESIGN AND METHODS

This was a retrospective cohort study from January 2006 to December 2015 using the electronic medical record in the Cleveland Clinic Health System (CCHS). Participants included 50,439 patients with type 2 diabetes receiving care in the CCHS. Number of severe hypoglycemia events and associated patient characteristics were identified.

RESULTS

The incidence proportion of severe hypoglycemia increased from 0.12% in 2006 to 0.31% in 2015 (P = 0.01). Compared with patients who did not experience severe hypoglycemia, those with severe hypoglycemia had similar median glycosylated hemoglobin (HbA1c) levels. More patients with severe hypoglycemia versus those without had a prior diagnosis of nonsevere hypoglycemia (9% vs. 2%, P < 0.001). Logistic regression confirmed an increased odds for severe hypoglycemia with insulin, sulfonylureas, increased number of diabetes medications, history of nonsevere hypoglycemia (odds ratio [OR] 3.01, P < 0.001), HbA1c <6% (42 mmol/mol) (OR 1.95, P < 0.001), black race, and increased Charlson comorbidity index. Lower odds of severe hypoglycemia were noted with higher BMI and use of metformin, dipeptidyl peptidase-4 inhibitor inhibitors, and glucagon-like peptide 1 agonists.

CONCLUSIONS

In this retrospective study of patients with type 2 diabetes with severe hypoglycemia, patient characteristics were identified. Patients with severe hypoglycemia had previous nonsevere hypoglycemia diagnoses more frequently than those without. Identifying patients at high risk at the point of care can allow for change in modifiable risk factors and prevention of severe hypoglycemia events.




Day-and-Night Closed-Loop Insulin Delivery in a Broad Population of Pregnant Women With Type 1 Diabetes: A Randomized Controlled Crossover Trial

2018-03-13T06:57:28-07:00

OBJECTIVE

Despite advances in technology, optimal glucose control remains elusive and neonatal complications ubiquitous in type 1 diabetes (T1D) pregnancy. Our aim was to examine the safety, efficacy, and longer-term feasibility of day-and-night closed-loop insulin delivery.

RESEARCH DESIGN AND METHODS

We recruited 16 pregnant women (mean [SD]: age 32.8 [5.0] years, T1D duration 19.4 [10.2] years, HbA1c 8.0% [1.1%], BMI 26.6 [4.4] kg/m2) to an open-label, randomized, crossover trial. Participants completed 28 days of closed-loop and sensor-augmented pump (SAP) insulin delivery separated by a washout period. Afterward, participants could continue to use the closed-loop system up to 6 weeks postpartum. The primary end point was the proportion of time with glucose levels within the target range (63–140 mg/dL).

RESULTS

The proportion of time with glucose levels within target was comparable during closed-loop and SAP insulin delivery (62.3 vs. 60.1% [95% CI –4.1 to 8.3%]; P = 0.47). Mean glucose and time spent hyperglycemic >140 mg/dL also did not differ (131.4 vs. 131.4 mg/dL [P = 0.85] and 36.6 vs. 36.1% [P = 0.86], respectively). During closed-loop, fewer hypoglycemic episodes occurred (median [range] 8 [1–17] vs. 12.5 [1–53] over 28 days; P = 0.04) and less time at <63 mg/dL (1.6 vs. 2.7%; P = 0.02). Hypoglycemia <50 mg/dL (0.24 vs. 0.47%; P = 0.03) and low blood glucose index (1.0 vs. 1.4; P = 0.01) were lower. Less nocturnal hypoglycemia (2300–0700 h) during closed-loop therapy (1.1 vs. 2.7%; P = 0.008) and a trend toward higher overnight time in target (67.7 vs. 60.6%; P = 0.06) were found.

CONCLUSIONS

Closed-loop insulin delivery was associated with comparable glucose control and significantly less hypoglycemia than SAP therapy. Larger, longer duration multicenter trials are now indicated to determine clinical efficacy of closed-loop insulin delivery in T1D pregnancy and the impact on neonatal outcomes.




Predicting the Effect of Fenofibrate on Cardiovascular Risk for Individual Patients With Type 2 Diabetes Mellitus

2018-02-22T06:51:08-08:00

OBJECTIVE

In clinical trials, treatment with fenofibrate did not reduce the incidence of major cardiovascular events (MCVE) in patients with type 2 diabetes mellitus (T2DM). However, treatment effects reported by trials comprise patients who respond poorly and patients who respond well to fenofibrate. Our aim was to use statistical modeling to estimate the expected treatment effect of fenofibrate for individual patients with T2DM.

RESEARCH DESIGN AND METHODS

To estimate individual risk, the FIELD risk model, with 5-year MCVE as primary outcome, was externally validated in T2DM patients from ACCORD and the SMART observational cohort. Fenofibrate treatment effect was estimated in 17,142 T2DM patients from FIELD, ACCORD, and SMART. Individual treatment effect, expressed as absolute risk reduction (ARR), is the difference between treated and untreated MCVE risk. Results were stratified for patients with and without dyslipidemia (i.e., high triglycerides and low LDL cholesterol).

RESULTS

External validation of the FIELD risk model showed good calibration and moderate discrimination in ACCORD (C-statistic 0.67 [95% CI 0.65–0.69]) and SMART (C-statistic 0.66 [95% CI 0.63–0.69]). Median 5-year MCVE risk in all three studies combined was 6.7% (interquartile range [IQR] 4.0–11.7) in patients without (N = 13,224), and 9.4% (IQR 5.4–16.1%) in patients with (N = 3,918), dyslipidemia. The median ARR was 2.15% (IQR 1.23–3.68) in patients with dyslipidemia, corresponding with a number needed to treat (NNT) of 47, and 0.22% (IQR 0.13–0.38) in patients without dyslipidemia (NNT 455).

CONCLUSIONS

In individual patients with T2DM, there is a wide range of absolute treatment effect of fenofibrate, and overall the fenofibrate treatment effect was larger in patients with dyslipidemia. The method of individualized treatment effect prediction of fenofibrate on MCVE risk reduction in T2DM can be used to guide clinical decision-making.




Trends in Hospital Admission for Diabetic Ketoacidosis in Adults With Type 1 and Type 2 Diabetes in England, 1998-2013: A Retrospective Cohort Study

2018-01-31T06:28:34-08:00

OBJECTIVE

This study determined trends in hospital admission for diabetic ketoacidosis (DKA) in adults with type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) from 1998 to 2013 in England.

RESEARCH DESIGN AND METHODS

The study population included 23,246 adults with T1DM and 241,441 adults with T2DM from the Clinical Practice Research Datalink and Hospital Episode Statistics. All hospital admissions for DKA as the primary diagnosis from 1998 to 2013 were identified. Trends in hospital admission for DKA in incidence, length of hospital stay, 30-day all-cause readmission rate, and 30-day and 1-year all-cause mortality rates were determined using joinpoint regression, negative binomial regression, and logistic regression models.

RESULTS

For T1DM, the incidence of hospital admission for DKA increased between 1998 and 2007 and remained static until 2013. The incidence in 2013 was higher than that in 1998 (incidence rate ratio 1.53 [95% CI 1.09–2.16]). For T2DM, the incidence increased 4.24% (2.82–5.69) annually between 1998 and 2013. The length of hospital stay decreased over time for both diabetes types (P ≤ 0.0004). Adults with T1DM were more likely to be discharged within 2 days compared with adults with T2DM (odds ratio [OR] 1.28 [1.07–1.53]). The 30-day readmission rate was higher in T1DM than in T2DM (OR 1.61 [1.04–2.50]) but remained unchanged for both diabetes types over time. Trends in 30-day and 1-year all-cause mortality rates were also stable, with no difference by diabetes type.

CONCLUSIONS

In the previous 2 decades in England, hospitalization for DKA increased in adults with T1DM and in those with T2DM, and associated health care performance did not improve except decreased length of hospital stay.




Intensive Blood Pressure Lowering in Patients With and Patients Without Type 2 Diabetes: A Pooled Analysis From Two Randomized Trials

2017-12-06T06:50:34-08:00

OBJECTIVE

The Action to Control Cardiovascular Risk in Diabetes Blood Pressure (ACCORD-BP) study did not find a significant beneficial effect of intensive systolic blood pressure (SBP) lowering on cardiovascular events in hypertensive patients with type 2 diabetes mellitus (T2DM), while the Systolic Blood Pressure Intervention Trial (SPRINT) did find a significant beneficial effect in patients without T2DM. The objective of this analysis was to assess the effect of both T2DM and baseline cardiovascular disease (CVD) risk on the treatment effect of intensive blood pressure lowering.

RESEARCH DESIGN AND METHODS

The individual patient data from the ACCORD-BP and SPRINT studies were pooled and follow-up durations harmonized. Both studies randomized hypertensive patients to an SBP target of <120 mmHg or a target of <140 mmHg. The composite primary end point consisted of unstable angina, myocardial infarction, acute heart failure, stroke, and cardiovascular death. The interaction between intensive blood pressure lowering and both T2DM and 10-year cardiovascular risk was assessed using Cox proportional hazards models.

RESULTS

The cohort consisted of 14,094 patients with mean age 66 ± 8.9 years and mean baseline SBP 139.5 ± 15.6 mmHg; 33.6% had T2DM. The hazard ratio for the primary composite end point was 0.82 (95% CI 0.73–0.93) (P = 0.0017). The interaction between intensive blood pressure lowering and T2DM was nonsignificant (P = 0.13). The 10-year cardiovascular risk was higher in primary prevention patients with T2DM, but risk did not interact with the treatment effect (P = 0.84).

CONCLUSIONS

Intensive blood pressure lowering may have a similar favorable effect and appears to decrease cardiovascular events in both patients with and patients without T2DM.