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.

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.

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.

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.

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 risk on the treatment effect of intensive blood pressure lowering.

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.

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).

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

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.

Data were collected from 251 patients enrolled in a randomized clinical trial testing the effectiveness of a self-management intervention assisted by a promotora (Hispanic community health worker). 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.

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.

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.

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.

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 A_1c (HbA_1c) 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 HbA_1c over the 12 months after the survey, controlling for mean prior 12-month HbA_1c, time, insulin use, age, and race/ethnicity.

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 HbA_1c levels. Autonomy support moderated the relationship between diabetes distress and HbA_1c (B = –0.13 [SE 0.06]; P = 0.027). Greater diabetes distress was associated with higher HbA_1c at low (B = 0.21 [SE 07]; P = 0.002) but not high (B = 0.01 [SE 0.07]; P = 0.890) levels of autonomy support.

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.

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.

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.

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 (HbA_1c) 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), HbA_1c <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 inhibitors, and glucagon-like peptide 1 agonists.

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.

Limited studies have examined the association between diabetes and HbA_1c with postoperative outcomes. We investigated the association of diabetes, defined categorically, and the association of HbA_1c as a continuous measure, with postoperative outcomes.

In this prospective, observational study, we measured the HbA_1c 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 HbA_1c ≥6.5% (48 mmol/mol) or with prediabetes if they had an HbA_1c between 5.7 and 6.4% (39 and 48 mmol/mol). Patients with an HbA_1c <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.

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 HbA_1c 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.

Almost one-third of surgical inpatients age ≥54 years had diabetes. Diabetes and higher HbA_1c were independently associated with a higher risk of adverse outcomes after surgery.

International studies on childhood type 1 diabetes (T1D) have focused on whole-country mean HbA_1c levels, thereby concealing potential variations within countries. We aimed to explore the variations in HbA_1c across and within eight high-income countries to best inform international benchmarking and policy recommendations.

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, U.S., 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 HbA_1c 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.

Sweden had the lowest mean HbA_1c (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 HbA_1c (61–62 mmol/mol [7.7–7.8%]) but showed the largest center variations (ICC ~15%). Centers in England, Wales, and the U.S. 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 HbA_1c levels (5.6 mmol/mol [0.5%] per 5 mmol/mol [0.5%] increase in center SD of HbA_1c values of all children attending a specific center).

At similar average levels of HbA_1c, 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.

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.

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. HbA_1c 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 HbA_1c) was analyzed using hierarchical linear mixed models.

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 HbA_1c (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 HbA_1c (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).

Food insecurity is associated with higher HbA_1c, 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.

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).

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 or older 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.

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.

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.

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.

A national prevalent cohort of 302,339 individuals diagnosed with diabetes between 2005 and 2014 was 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.

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.

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.

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).

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.

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.

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.

A new opportunistic community-based strategy was launched in Japan in April 2014 to detect lifestyle-related diseases, including diabetes, by creating Specimen Measurement Offices (SMOs). SMOs offer walk-in fingertip HbA_1c testing. This article aimed to assess the value-for-money of HbA_1c testing services at SMOs by conducting a cost-effectiveness analysis.

We compared two scenarios: 1) status quo, defined as HbA_1c testing that is available only through conventional screening, and 2) HbA_1c testing available at SMOs as a complement to the status quo scenario. The model consisted of a screening module with a decision tree and a disease progression module with a Markov model. We calculated incremental cost-effectiveness ratios (i.e., cost per quality-adjusted life-years [QALYs]) over the lifetime analytic horizon as the primary end point of the cost-effectiveness analysis. In this model, we assumed the participant cohort to be people 40–74 years of age who sought walk-in fingertip HbA_1c testing at SMOs on the premises of community pharmacies. Costs and outcomes were discounted at a rate of 3%. The cost-effectiveness was analyzed from a societal perspective.

The incremental cost per individual for those 40–74 years of age was estimated to be –527 U.S. dollars (USD) (–52,722 Japanese yen [JPY]) for HbA_1c testing at SMOs compared with the status quo. Incremental effectiveness was estimated to be 0.0203 QALYs for HbA_1c testing at SMOs compared with the status quo. Therefore, this cost-effectiveness analysis showed that compared with the status quo, HbA_1c testing at SMOs was more effective and had lower cost for the population studied.

We consider our results to be robust because most simulations were under the threshold of USD 50,000 (JPY 5,000,000) per QALYs gained, by sensitivity analysis. These results will be useful to managers of pharmacies or other health institutions and/or policy makers in local government.

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

In the Multiple Daily Injections and Continuous Glucose Monitoring in Diabetes (DIAMOND) trial, 158 patients with T1D and HbA_1c ≥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.

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 HbA_1c (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.

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.

Insulin resistance and nonalcoholic fatty liver 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+) nonalcoholic fatty liver and nonalcoholic steatohepatitis (NASH) and 7 healthy lean individuals undergoing tissue biopsies during bariatric or elective abdominal surgery.

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 were measured to assess mitochondrial function, oxidative stress, and inflammatory activity.

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 lactosylceramide 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.

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.

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.

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).

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).

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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 those 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.

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).

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).

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.

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.

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).

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.

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.

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.

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.

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.

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.

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.

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

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.

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 the 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.

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

The implementation of the Chronic Care Model (CCM) improves health care quality. We examined the sustained effectiveness of multicomponent integrated care in type 2 diabetes.

We searched PubMed and Ovid MEDLINE (January 2000–August 2016) and identified randomized controlled trials comprising two or more quality improvement strategies from two or more domains (health system, health care providers, or patients) lasting ≥12 months with one or more clinical outcomes. Two reviewers extracted data and appraised the reporting quality.

In a meta-analysis of 181 trials (N = 135,112), random-effects modeling revealed pooled mean differences in HbA_1c of –0.28% (95% CI –0.35 to –0.21) (–3.1 mmol/mol [–3.9 to –2.3]), in systolic blood pressure (SBP) of –2.3 mmHg (–3.1 to –1.4), in diastolic blood pressure (DBP) of –1.1 mmHg (–1.5 to –0.6), and in LDL cholesterol (LDL-C) of –0.14 mmol/L (–0.21 to –0.07), with greater effects in patients with LDL-C ≥3.4 mmol/L (–0.31 vs. –0.10 mmol/L for <3.4 mmol/L; P_difference = 0.013), studies from Asia (HbA_1c –0.51% vs. –0.23% for North America [–5.5 vs. –2.5 mmol/mol]; P_difference = 0.046), and studies lasting >12 months (SBP –3.4 vs. –1.4 mmHg, P_difference = 0.034; DBP –1.7 vs. –0.7 mmHg, P_difference = 0.047; LDL-C –0.21 vs. –0.07 mmol/L for 12-month studies, P_difference = 0.049). Patients with median age <60 years had greater HbA_1c reduction (–0.35% vs. –0.18% for ≥60 years [–3.8 vs. –2.0 mmol/mol]; P_difference = 0.029). Team change, patient education/self-management, and improved patient-provider communication had the largest effect sizes (0.28–0.36% [3.0–3.9 mmol/mol]).

Despite the small effect size of multicomponent integrated care (in part attenuated by good background care), team-based care with better information flow may improve patient-provider communication and self-management in patients who are young, with suboptimal control, and in low-resource settings.