To determine whether a mindfulness-based stress reduction (MBSR) intervention is effective for reducing psychosocial distress (i.e., depression, psychosocial stress) and the progression of nephropathy (i.e., albuminuria) and for improving the subjective health status of patients with type 2 diabetes.

Patients with type 2 diabetes and microalbuminuria were randomized to a mindfulness-based intervention (n = 53) or a treatment-as-usual control (n = 57) group. The study is designed to investigate long-term outcomes over a period of 5 years. We present data up to the first year of follow-up (FU).

At FU, the MBSR group showed lower levels of depression (d = 0.71) and improved health status (d = 0.54) compared with the control group. No significant differences in albuminuria were found. Per-protocol analysis also showed higher stress reduction in the intervention group (d = 0.64).

MBSR intervention achieved a prolonged reduction in psychosocial distress. The effects on albuminuria will be followed up further.

Given the transient nature of exercise-induced improvements in insulin sensitivity, it has been speculated that daily exercise is preferred to maximize the benefits of exercise for glycemic control. The current study investigates the impact of daily exercise versus exercise performed every other day on glycemic control in type 2 diabetic patients.

Thirty type 2 diabetic patients (age 60 ± 1 years, BMI 30.4 ± 0.7 kg/m², and HbA_1c 7.2 ± 0.2%) participated in a randomized crossover experiment. Subjects were studied on three occasions for 3 days under strict dietary standardization but otherwise free-living conditions. Blood glucose homeostasis was assessed by continuous glucose monitoring over 48 h during which subjects performed no exercise (control) or 60 min of cycling exercise (50% maximal workload capacity) distributed either as a single session performed every other day or as 30 min of exercise performed daily.

The prevalence of hyperglycemia (blood glucose >10 mmol/L) was reduced from 7:40 ± 1:00 h:min per day (32 ± 4% of the time) to 5:46 ± 0:58 and 5:51 ± 0:47 h:min per day, representing 24 ± 4 and 24 ± 3% of the time, when exercise was performed either daily or every other day, respectively (P < 0.001 for both treatments). No differences were observed between the impact of daily exercise and exercise performed every other day.

A short 30-min session of moderate-intensity endurance-type exercise substantially reduces the prevalence of hyperglycemia throughout the subsequent day in type 2 diabetic patients. When total work is being matched, daily exercise does not further improve daily glycemia compared with exercise performed every other day.

To determine variables associated with glycemic and body weight responses when adding exenatide to basal insulin–treated type 2 diabetes.

Exploratory subgroup analyses based on baseline A1C, disease duration, and BMI of a 30-week study comparing exenatide twice daily to placebo, added to optimized insulin glargine (intent-to-treat analysis: 137 exenatide; 122 placebo).

Exenatide participants had greater A1C reductions compared with optimized insulin glargine alone, irrespective of baseline A1C (P < 0.001). Exenatide participants with longer diabetes duration and those with lower BMI had greater A1C reductions (P < 0.01). Exenatide participants lost more weight, regardless of baseline A1C or BMI (P < 0.05). Exenatide participants with longer diabetes duration lost the most weight (P < 0.001).

Exenatide added to optimized basal insulin was associated with improved glycemic control and weight loss, irrespective of baseline A1C, diabetes duration, and BMI. Changes were evident in modestly obese patients and in those with longer diabetes duration.

In patients with type 2 diabetes, but not type 1 diabetes, abnormal secretion of incretins in response to oral nutrients has been described. In healthy youths, we recently reported accentuated glucagon-like peptide 1 (GLP-1) secretion in response to a diet soda sweetened with sucralose and acesulfame-K. In this study, we examined the effect of diet soda on gut hormones in youths with diabetes.

Subjects aged 12–25 years with type 1 diabetes (n = 9) or type 2 diabetes (n = 10), or healthy control participants (n = 25) drank 240 mL cola-flavored caffeine-free diet soda or carbonated water, followed by a 75-g glucose load, in a randomized, cross-over design. Glucose, C-peptide, GLP-1, glucose-dependent insulinotropic peptide (GIP), and peptide Tyr-Tyr (PYY) were measured for 180 min. Glucose and GLP-1 have previously been reported for the healthy control subjects.

GLP-1 area under the curve (AUC) was 43% higher after ingestion of diet soda versus carbonated water in individuals with type 1 diabetes (P = 0.020), similar to control subjects (34% higher, P = 0.029), but was unaffected by diet soda in patients with type 2 diabetes (P = 0.92). Glucose, C-peptide, GIP, and PYY AUC were not statistically different between the two conditions in any group.

Ingestion of diet soda before a glucose load augmented GLP-1 secretion in type 1 diabetic and control subjects but not type 2 diabetic subjects. GIP and PYY secretion were not affected by diet soda. The clinical significance of this increased GLP-1 secretion, and its absence in youths with type 2 diabetes, needs to be determined.

Patients with type 1 diabetes aged 8–60 years with HbA_1c ≥8% were randomly assigned to three groups (1:1:1). Outcomes for glucose control were assessed at 1 year for two modes of CGM (group 1: patient led; group 2: physician driven) versus conventional self-monitoring of blood glucose (group 3: control).

A total of 257 subjects with type 1 diabetes underwent screening. Of these, 197 were randomized, with 178 patients completing the study (age: 36 ± 14 years; HbA_1c: 8.9 ± 0.9%). HbA_1c improved similarly in both CGM groups and was reduced compared with the control group (group 1 vs. group 3: –0.52%, P = 0.0006; group 2 vs. group 3: –0.47%, P = 0.0008; groups 1 + 2 vs. group 3: –0.50%, P < 0.0001). The incidence of hypoglycemia was similar in the three groups. Patient SF-36 questionnaire physical health score improved in both experimental CGM groups (P = 0.004). Sensor consumption was 34% lower in group 2 than in group 1 (median [Q1–Q3] consumption: group 1: 3.42/month [2.20–3.91] vs. group 2: 2.25/month [1.27–2.99], P = 0.001).

Both patient-led and physician-driven CGM provide similar long-term improvement in glucose control in patients with poorly controlled type 1 diabetes, but the physician-driven CGM mode used fewer sensors.

To compare the incidences of severe hypoglycemia and corresponding clinical circumstances in a German population between 2007–2010 and 1997–2000.

A screening for severe hypoglycemia was performed in the Lippe-Detmold area in Germany to sensitively detect severe hypoglycemia. This was defined as a symptomatic event requiring treatment with intravenous glucose and being confirmed by a blood glucose measurement of <50 mg/dL.

Severe hypoglycemia increased considerably from 264 events in 1997–2000 to 495 events in 2007–2010, which translated into an increase in frequency of severe hypoglycemia among all emergency admissions from 0.68 to 0.83% (P = 0.015). This was mostly related to intensification of antihyperglycemic therapy, particularly in the increasingly morbid group of hypoglycemic patients with type 2 diabetes indicated by lower HbA_1c, more comedication (3.3 vs. 7.7 drugs), and more concomitant diseases (3.6 vs. 4.4) (all P values <0.001).

Within a 10-year period, there was an intensification of antihyperglycemic therapy in increasingly comorbid subjects, leading to a considerably higher incidence of severe hypoglycemia.

Observational studies show breaking up prolonged sitting has beneficial associations with cardiometabolic risk markers, but intervention studies are required to investigate causality. We examined the acute effects on postprandial glucose and insulin levels of uninterrupted sitting compared with sitting interrupted by brief bouts of light- or moderate-intensity walking.

Overweight/obese adults (n = 19), aged 45–65 years, were recruited for a randomized three-period, three-treatment acute crossover trial: 1) uninterrupted sitting; 2) seated with 2-min bouts of light-intensity walking every 20 min; and 3) seated with 2-min bouts of moderate-intensity walking every 20 min. A standardized test drink was provided after an initial 2-h period of uninterrupted sitting. The positive incremental area under curves (iAUC) for glucose and insulin (mean [95% CI]) for the 5 h after the test drink (75 g glucose, 50 g fat) were calculated for the respective treatments.

The glucose iAUC (mmol/L) ⋅ h after both activity-break conditions was reduced (light: 5.2 [4.1–6.6]; moderate: 4.9 [3.8–6.1]; both P < 0.01) compared with uninterrupted sitting (6.9 [5.5–8.7]). Insulin iAUC (pmol/L) ⋅ h was also reduced with both activity-break conditions (light: 633.6 [552.4–727.1]; moderate: 637.6 [555.5–731.9], P < 0.0001) compared with uninterrupted sitting (828.6 [722.0–950.9]).

Interrupting sitting time with short bouts of light- or moderate-intensity walking lowers postprandial glucose and insulin levels in overweight/obese adults. This may improve glucose metabolism and potentially be an important public health and clinical intervention strategy for reducing cardiovascular risk.

To investigate the effect of flexible intensive insulin therapy (FIIT) and an automated bolus calculator (ABC) in a Danish type 1 diabetes population treated with multiple daily injections. Furthermore, to test the feasibility of teaching FIIT in a 3-h structured course.

The BolusCal Study was a 16-week randomized, controlled, open-label, three-arm parallel, clinical study of 51 adults with type 1 diabetes. Patients aged 18–65 years in poor metabolic control (HbA_1c 8.0–10.5%) were randomized to the Control (n = 8), CarbCount (n = 21), or CarbCountABC (n = 22) arm. During a 3-h group teaching, the Control arm received FIIT education excluding carbohydrate counting. CarbCount patients were taught FIIT and how to count carbohydrates. CarbCountABC group teaching included FIIT and carbohydrate counting and patients were provided with an ABC.

At 16 weeks, the within-group change in HbA_1c was –0.1% (95% CI –1.0 to 0.7%; P = 0.730) in the Control arm, –0.8% (–1.3 to –0.3%; P = 0.002) in the CarbCount arm, and –0.7% (–1.0 to –0.4%; P < 0.0001) in the CarbCountABC arm. The difference in change in HbA_1c between CarbCount and CarbCountABC was insignificant. Adjusting for baseline HbA_1c in a regression model, the relative change in HbA_1c was –0.6% (–1.2 to 0.1%; P = 0.082) in CarbCount and –0.8% (–1.4 to –0.1%; P = 0.017) in CarbCountABC. Treatment satisfaction measured by the Diabetes Treatment Satisfaction Questionnaire (status version) improved in all study arms, but the improvement was significantly greater in CarbCountABC.

FIIT and carbohydrate counting were successfully taught in 3 h and improved metabolic control and treatment satisfaction. Concurrent use of an ABC improved treatment satisfaction further.

A1C was measured as part of routine care (clinical A1C) or in the core laboratory (laboratory A1C, results unavailable to clinicians). GTI predictors were identified using hierarchical Poisson regression.

Of 1,274 patients, 886 (70%) had clinical A1C and an additional 263 had laboratory A1C measured. Overall, A1C was <7% in 419 (37%), 7–9% in 415 (36%), and >9% in 315 patients (27%). GTI occurred in 31% of patients and was more frequent in those with clinical A1C both before (34 vs. 24%, P < 0.001) and after multivariable adjustment (relative risk 1.34 [95% CI 1.12–1.62] vs. no clinical A1C).

Long-term glucose control is poor in most AMI patients with DM, but only a minority of patients undergo GTI at discharge. Inpatient A1C assessment is strongly associated with intensification of glucose-lowering therapy.

Disordered mineral metabolism is a common complication of chronic kidney disease (CKD) and a novel risk factor for CKD progression, cardiovascular disease, and mortality. Although diabetes is the leading cause of CKD and is associated with worse clinical outcomes than other etiologies, few studies have evaluated mineral metabolism in CKD according to diabetes status.

Using the Chronic Renal Insufficiency Cohort Study, we tested the hypothesis that diabetes is independently associated with lower serum calcium and higher serum phosphate, parathyroid hormone (PTH), and fibroblast growth factor 23 (FGF23).

Compared with participants without diabetes (n = 1,936), those with diabetes (n = 1,820) were more likely to have lower estimated glomerular filtration rate (eGFR), lower serum albumin, and higher urinary protein excretion (all P < 0.001). Unadjusted serum phosphate, PTH, and FGF23 levels were higher and calcium was lower among those with compared with those without diabetes (all P < 0.001). After multivariate adjustment, diabetes remained a significant predictor of serum phosphate, PTH, and FGF23 but not calcium. The eGFR cut point at which 50% of participants met criteria for secondary hyperparathyroidism or elevated FGF23 was higher in participants with diabetes compared with those without (PTH: eGFR 30–39 vs. 20–29, P < 0.001; FGF23: eGFR 50–59 vs. 40–49, P < 0.001).

Disordered mineral metabolism begins earlier in the course of CKD and is more severe among CKD patients with compared with those without diabetes. Future studies should explore mechanisms for these differences and whether they contribute to excess risks of adverse clinical outcomes among diabetic patients with CKD.

Metformin and statins have shown promise for cancer prevention. This study assessed whether the effect of metformin on prostate cancer (PCa) incidence varied by statin use among type 2 diabetic patients.

The study cohort consisted of 5,042 type 2 diabetic male patients seen in the Veteran Administration Health Care System who were without prior cancer and were prescribed with metformin or sulfonylurea as the exclusive hypoglycemic medication between fiscal years 1999 and 2005. Cox proportional hazards analyses were conducted to assess the differential hazard ratio (HR) of PCa due to metformin by statin use versus sulfonylurea use, where propensity scores of metformin and statin use were adjusted to account for imbalances in baseline covariates across medication groups.

Mean follow-up was ~5 years, and 7.5% had a PCa diagnosis. Statin use modified the effect of metformin on PCa incidence (P < 0.0001). Metformin was associated with a significantly reduced PCa incidence among patients on statins (HR 0.69 [95% CI 0.50–0.92]; 17 cases/533 metformin users vs. 135 cases/2,404 sulfonylureas users) and an increased PCa incidence among patients not on statins (HR 2.15 [1.83–2.52]; 22 cases/175 metformin users vs. 186 cases/1,930 sulfonylureas users). The HR of PCa incidence for those taking metformin and statins versus those taking neither medication was 0.32 (0.25–0.42).

Among men with type 2 diabetes, PCa incidence among metformin users varied by their statin use. The potential beneficial influence on PCa by combination use of metformin and statin may be due to synergistic effects.

An on-drug/off-drug ancillary study to the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Lipid Trial to investigate posttrial changes in serum creatinine and cystatin C. Eligible participants were recruited into a prospective, nested, three-group study based on retrospective on-trial serum creatinine levels: fenofibrate case subjects (n = 321, ≥20% increase after 3 months of therapy); fenofibrate control subjects (n = 175, ≤2% increase); and placebo control subjects (n = 565). Serum creatinine and cystatin C were measured at trial end and 6–8 weeks after discontinuation of trial therapy.

At trial end, case subjects had the highest adjusted serum creatinine (± SE) mg/dL (1.11 ± 0.02) and the lowest adjusted estimated glomerular filtration rate (eGFR) (± SE) mL/min/1.73 m² (68.4 ± 1.0) versus control subjects (1.01 ± 0.02; 74.8 ± 1.3) and placebo subjects (0.98 ± 0.01; 77.8 ± 0.7). After 51 days off-drug, serum creatinine in case subjects was still higher (0.97 ± 0.02) and eGFR still lower (77.8 ± 1.0) than control subjects (0.90 ± 0.02; 81.8 ± 1.3) but not different from placebo subjects (0.99 ± 0.01; 76.6 ± 0.7). Changes in serum cystatin C recapitulated the serum creatinine changes.

Participants with significant initial on-trial increases in serum creatinine (≥20%) returned to the same level of renal function as participants receiving placebo while participants who had ≤2% increase in serum creatinine had net preservation of renal function compared with the same unselected placebo reference group. The fenofibrate-associated on-trial increases in serum creatinine were reversible, and the reversal was complete after 51 days off-drug. The similarity of the cystatin C results suggests that the mechanism of this change is not specific for serum creatinine.

Glucokinase (GCK) acts as a component of the "glucose sensor" in pancreatic β-cells and possibly in other tissues, including the brain. However, >99% of GCK in the body is located in the liver, where it serves as a "gatekeeper", determining the rate of hepatic glucose phosphorylation. Mutations in GCK are a cause of maturity-onset diabetes of the young (MODY), and GCKR, the regulator of GCK in the liver, is a diabetes susceptibility locus. In addition, several GCK activators are being studied as potential regulators of blood glucose. The ability to estimate liver GCK activity in vivo for genetic and pharmacologic studies may provide important physiologic insights into the regulation of hepatic glucose metabolism.

Here we introduce a simple, linear, two-compartment kinetic model that exploits lactate and glucose kinetics observed during the frequently sampled intravenous glucose tolerance test (FSIGT) to estimate liver GCK activity (K_GK), glycolysis (K₁₂), and whole body fractional lactate clearance (K₀₁).

To test our working model of lactate, we used cross-sectional FSIGT data on 142 nondiabetic individuals chosen at random from the Finland–United States Investigation of NIDDM Genetics study cohort. Parameters K_GK, K₁₂, and K₀₁ were precisely estimated. Median model parameter estimates were consistent with previously published values.

This novel model of lactate kinetics extends the utility of the FSIGT protocol beyond whole-body glucose homeostasis by providing estimates for indices pertaining to hepatic glucose metabolism, including hepatic GCK activity and glycolysis rate.

We used prospective observational data from Veterans Affairs Medical Centers in Washington, DC, and Palo Alto, California. Our cohort (N = 4,156; mean age 60 ± 10.3 years) consisted of 2,013 African Americans (mean age, 59.5 ± 9.9 years), 2,000 Caucasians (mean age, 60.8 ± 10.5 years), and 143 of unknown race/ethnicity. BMI, cardiac risk factors, medications, and peak exercise capacity in metabolic equivalents (METs) were assessed during 1986 and 2010. All-cause mortality was assessed across BMI and fitness categories.

There were 1,074 deaths during a median follow-up period of 7.5 years. A paradoxic BMI–mortality association was observed, with significantly higher risk among those with a BMI between 18.5 and 24.9 kg/m² (hazard ratio [HR] 1.70 [95% CI 1.36–2.1]) compared with the obese category (BMI ≥35 kg/m²). This association was accentuated in African Americans (HR 1.95 [95% CI 1.44–2.63]) versus Caucasians (HR 1.53 [1.0–2.1]). The fitness–mortality risk association for the entire cohort and within BMI categories was inverse, independent, and graded. Mortality risks were 12% lower for each 1-MET increase in exercise capacity, and ~35–55% lower for those with an exercise capacity >5 METs compared with the least fit (≤5 METs).

A paradoxic BMI–mortality risk association was observed in African American and Caucasian patients with diabetes. The exercise capacity–mortality risk association was inverse, independent, and graded in all BMI categories but was more potent in those with a BMI ≥25 kg/m².

Two consecutive population-based surveys for type 2 diabetes were conducted in randomly selected adults aged 35–74 years in Shanghai in 2002–2003 (n = 12,329) and in 2009 (n = 7,423). Diagnosed type 2 diabetes was determined based on self-report, whereas those undiagnosed were identified by measured fasting and postload glucose according to 2009 American Diabetes Association criteria.

Age-standardized prevalence of diagnosed and undiagnosed type 2 diabetes increased from 5.1 and 4.6% in 2002–2003 to 7.4 and 5.2% in 2009. The prevalence of type 2 diabetes increased with age and was higher among men and in urban residents in both surveys (P < 0.001). Between the two surveys, the increase in the prevalence was more evident in the rural population (P < 0.001) and appeared more rapid in younger birth cohorts (P < 0.05).

Our results suggest that Shanghai has experienced an increasing burden of type 2 diabetes.

Diabetes and hypertension often co-occur and share risk factors. Hypertension is known to predict diabetes. However, hyperglycemia also may be independently associated with future development of hypertension. We investigated glycated hemoglobin (HbA_1c) as a predictor of incident hypertension.

We conducted a prospective analysis of 9,603 middle-aged participants in the Atherosclerosis Risk in Communities Study without hypertension at baseline. Using Cox proportional hazards models, we estimated the association between HbA_1c at baseline and incident hypertension by two definitions 1) self-reported hypertension during a maximum of 18 years of follow-up and 2) measured blood pressure or hypertension medication use at clinic visits for a maximum of 9 years of follow-up.

We observed 4,800 self-reported and 1,670 visit-based hypertension cases among those without diagnosed diabetes at baseline. Among those with diagnosed diabetes at baseline, we observed 377 self-reported and 119 visit-based hypertension cases. Higher baseline HbA_1c was associated with an increased risk of hypertension in subjects with and without diabetes. Compared with nondiabetic adults with HbA_1c <5.7%, HbA_1c in the prediabetic range (5.7–6.4%) was independently associated with incident self-reported hypertension (hazard ratio 1.14 [95% CI 1.06–1.23]) and visit-detected hypertension (1.17 [1.03–1.33]).

We observed that individuals with elevated HbA_1c, even without a prior diabetes diagnosis, are at increased risk of hypertension. HbA_1c is a known predictor of incident heart disease and stroke. Our results suggest that the association of HbA_1c with cardiovascular risk may be partially mediated by the development of hypertension.

We assessed the impact of a diabetes incentive code introduced for primary care physicians in Ontario, Canada, in 2002 on quality of diabetes care at the population and patient level.

We analyzed administrative data for 757,928 Ontarians with diabetes to examine the use of the code and receipt of three evidence-based monitoring tests from 2006 to 2008. We assessed testing rates over time and before and after billing of the incentive code.

One-quarter of Ontarians with diabetes had an incentive code billed by their physician. The proportion receiving the optimal number of all three monitoring tests (HbA_1c, cholesterol, and eye tests) rose gradually from 16% in 2000 to 27% in 2008. Individuals who were younger, lived in rural areas, were not enrolled in a primary care model, or had a mental illness were less likely to receive all three recommended tests. Patients with higher numbers of incentive code billings in 2006–2008 were more likely to receive recommended testing but also were more likely to have received the highest level of recommended testing prior to introduction of the incentive code. Following the same patients over time, improvement in recommended testing was no greater after billing of the first incentive code than before.

The diabetes incentive code led to minimal improvement in quality of diabetes care at the population and patient level. Our findings suggest that physicians who provide the highest quality care prior to incentives may be those most likely to claim incentive payments.

We retrospectively assessed the age- and sex-specific incidence and relative risk of Parkinson disease (PD) in Taiwan’s diabetic population.

Study cohort included 603,416 diabetic patients and 472,188 nondiabetic control subjects. Incidence rate and relative risk of PD (ICD-9-CM 332.0) were evaluated.

The incidence of PD was 3.59 and 2.15 per 10,000 person-years for the diabetic and control group, respectively, representing a covariate adjusted hazard ratio (HR) of 1.61 (95% CI 1.56–1.66), which was substantially reduced to 1.37 (1.32–1.41) after adjusting for medical visits. Diabetes was associated with a significantly elevated risk of PD in all sex and age stratifications except in young women, with the highest HR noted for young men aged 21–40 years (2.10 [1.01–4.42]), followed by women aged 41–60 (2.05 [1.82–2.30]) and >60 years (1.65 [1.58–1.73]).

Diabetes is associated with an increased risk of PD onset in a Chinese population, and the relation is stronger in women and younger patients.

The study comprised 1,722 nondiabetic Japanese individuals aged 26–80 years. Fasting plasma glucose (FPG) and HbA_1c were measured annually for a mean of 9.5 (SD 1.8) years.

Diabetes occurred in 193 individuals (FPG ≥7.0 mmol/L, self-reported clinician-diagnosed diabetes, or HbA_1c ≥6.5%). Mean HbA_1c values were >5.6% each year before diagnosis in diabetes cases. Mean HbA_1c (5.69% [95% CI 5.50–5.88]) was higher in the 21 individuals who developed diabetes 10 years after the baseline examination than in nondiabetic individuals after 10 years (5.27% [5.25–5.28]). From 3 years to 1 year prediagnosis, HbA_1c increased 0.09% (SE 0.01)/year, reaching 5.90% (5.84–5.96) 1 year prediagnosis. In the entire group, marked increases in HbA_1c of 0.3% (SE 0.05%)/year and FPG of 0.63 (0.07) mmol/L/year predicted diabetes.

HbA_1c trajectory increased sharply after gradual long-term increases in diabetic individuals.

Subjects voluntarily undergoing upper endoscopy/colonoscopy as part of a medical examination at the National Taiwan University Hospital were recruited during 2009. Diagnosis of DM included past history of DM, fasting plasma glucose ≥126 mg/dL, or glycated hemoglobin (HbA_1c) ≥6.5%. Comparisons were made between diabetic and nondiabetic subjects, subjects with lower and higher HbA_1c levels, and diabetic subjects with and without complications, respectively, for their GI symptoms, noninvasive GI testing results, and endoscopic findings.

Among 7,770 study subjects, 722 (9.3%) were diagnosed with DM. The overall prevalence of GI symptoms was lower in DM subjects (30.3 vs. 35.4%, P = 0.006). In contrast, the prevalence of erosive esophagitis (34.3 vs. 28.6%, P = 0.002), Barrett's esophagus (0.6 vs. 0.1%, P = 0.001), peptic ulcer disease (14.8 vs. 8.5%, P < 0.001), gastric neoplasms (1.8 vs. 0.7%, P = 0.003), and colonic neoplasms (26.6 vs. 16.5%, P < 0.001) was higher in diabetic subjects. Diagnostic accuracy of immunochemical fecal occult blood test for colonic neoplasms was significantly decreased in DM (70.7 vs. 81.7%, P < 0.001). Higher HbA_1c levels were associated with a decrease of GI symptoms and an increase of endoscopic abnormalities. Diabetic subjects with complications had a higher prevalence of colonic neoplasms (39.2 vs. 24.5%, P = 0.002) than those without.

DM and higher levels of HbA_1c were associated with lower prevalence of GI symptoms but higher prevalence of endoscopic abnormalities.

Diabetes may increase the risk of acute pancreatitis (AP). We aimed to further investigate whether diabetes may also adversely affect outcomes of patients with AP.

In this retrospective cohort study, we compared 18,990 first-attack AP with diabetes to 37,980 matched control subjects from Taiwan’s National Health Insurance Research Database between 2000 and 2009. Primary outcomes were development of severe AP, defined by a modified Atlanta classification scheme, and hospital mortality. Analyses were performed using univariable and multivariable logistic regression model with generalized estimating equations accounting for hospital clustering effect.

After baseline characteristics were adjusted, AP patients with diabetes had a higher risk of a severe attack than their nondiabetic counterparts (adjusted odds ratio [OR] 1.21, 95% CI 1.16–1.26). When severity criteria were analyzed individually, diabetic AP patients had a 58% higher risk of intensive care unit admission and a 30% higher risk of local complications, but a 16% lower risk of gastrointestinal bleeding, than AP patients without diabetes. The risk of organ failure at least one system) was similar between the two groups. Conversely, AP patients with diabetes were associated with a lower risk of hospital mortality (adjusted OR 0.77, 95% CI 0.65–0.91).

Although diabetes may adversely affect the disease process of AP, it seems to protect patients from AP-related mortality.

The Australian Diabetes, Obesity and Lifestyle (AusDiab) study included 11,247 adults aged ≥25 years from 42 randomly selected areas of Australia. At baseline (1999–2000), diabetes status was defined using the World Health Organization criteria and HRF was assessed using the SF-36 questionnaire.

Overall, after 7.4 years of follow-up, 57 persons with diabetes and 105 without diabetes had died from CVD. In individuals with and without diabetes, HRF measures were significant predictors of increased CVD mortality. The CVD mortality risks among those with diabetes or impaired physical health component summary (PCS) alone were similar (diabetes only: hazard ratio 1.4 [95% CI 0.7–2.7]; impaired PCS alone: 1.5 [1.0–2.4]), while those with both diabetes and impaired PCS had a much higher CVD mortality (2.8 [1.6–4.7]) compared with those without diabetes and normal PCS (after adjustment for multiple covariates). Similar results were found for the mental health component summary.

This study demonstrates that the combination of diabetes and impaired HRF is associated with substantially higher CVD mortality. This suggests that, among those with diabetes, impaired HRF is likely to be important in the identification of individuals at increased risk of CVD mortality.

The association between platelet activity, diabetes, and glucometabolic control is uncertain. We aim to investigate mean platelet volume (MPV), a marker of platelet size and platelet activity, with the prevalence of diabetes, metabolic syndrome, and degree of glycemic control.

This is a retrospective analysis of 13,021 participants in the National Health and Nutrition Examination Survey from 1999 to 2004. Prevalence of diabetes was defined as nonfasting glucose >200 mg/dL, fasting glucose ≥126 mg/dL, or treatment with hypoglycemic agents. Presence of metabolic syndrome was determined by the National Cholesterol Education Program Adult Treatment Panel III definition. Odds ratios and 95% CIs were estimated by logistic regression.

MPV was significantly higher in subjects with diabetes (8.20 vs. 8.06 femtoliter [fL], P < 0.01) but not in subjects with metabolic syndrome (8.09 vs. 8.07 fL, P = 0.24). For the metabolic syndrome components, MPV was significantly higher in abdominal obesity (P = 0.03) and low HDL (P = 0.04), and not different in high blood pressure (P = 0.07), abnormal glucose metabolism (P = 0.71), or hypertriglyceridemia (P = 0.46). There was a significant correlation between MPV and glucose (P < 0.0001) and between MPV and hemoglobin A_1c (P < 0.0001) in subjects with diabetes. These correlations were no longer significant in those without diabetes. The adjusted odds of diabetes rose with increasing MPV levels and were most pronounced in subjects with MPV levels exceeding the 90th percentile (≥9.31 fL). The association between MPV and diabetes was most apparent in those with the poorest glucose control.

Mean platelet volume is strongly and independently associated with the presence and severity of diabetes.

Examine the association of prepregnancy habitual consumption of fruits and fruit juices and gestational diabetes mellitus (GDM) risk.

A prospective study among women with at least one singleton pregnancy in the Nurses’ Health Study II from 1991 to 2001.

Among 13,475 women, 860 reported a first diagnosis of GDM. The adjusted relative risks (RRs) for GDM from the lowest to highest quintile of whole fruit consumption were 1.00 (referent), 0.80 (95% CI 0.65–0.98), 0.90 (0.73–1.10), 0.80 (0.64–1.00), and 0.93 (0.76–1.16), respectively. The corresponding RRs for fruit juice were 1.00, 0.82 (0.66–1.01), 0.78 (0.63–0.96), 0.84 (0.68–1.04), and 1.00 (0.81–1.23).

These data suggest that prepregnancy higher consumption of whole fruits is not associated with an increased GDM risk. The association between fruit juices and GDM risk appears to be nonlinear.

To investigate the relationship between arterial stiffness and low-grade inflammation in subjects with type 1 diabetes without clinical cardiovascular disease.

Sixty-eight patients with type 1 diabetes and 68 age- and sex-matched healthy subjects were evaluated. Arterial stiffness was assessed by aortic pulse wave velocity (aPWV). Serum concentrations of high-sensitivity C-reactive protein (hsCRP), interleukin (IL)-6, and soluble fractions of tumor necrosis factor-α receptors 1 and 2 (sTNFαR1 and sTNFαR2, respectively) were measured. All statistical analyses were stratified by sex.

Subjects with diabetes had a higher aPWV compared with healthy control subjects (men: 6.9 vs. 6.3 m/s, P < 0.001; women: 6.4 vs. 6.0 m/s, P = 0.023). These differences remained significant after adjusting for cardiovascular risk factors. Men with diabetes had higher concentrations of hsCRP (1.2 vs. 0.6 mg/L; P = 0.036), IL-6 (0.6 vs. 0.3 pg/mL; P = 0.002), sTNFαR1 (2,739 vs. 1,410 pg/mL; P < 0.001), and sTNFαR2 (2,774 vs. 2,060 pg/mL; P < 0.001). Women with diabetes only had higher concentrations of IL-6 (0.6 vs. 0.4 pg/mL; P = 0.039). In men with diabetes, aPWV correlated positively with hsCRP (r = 0.389; P = 0.031) and IL-6 (r = 0.447; P = 0.008), whereas in women with diabetes no significant correlation was found. In men, multiple linear regression analysis showed that the following variables were associated independently with aPWV: age, BMI, type 1 diabetes, and low-grade inflammation (R² = 0.543). In women, these variables were age, BMI, mean arterial pressure, and type 1 diabetes (R² = 0.550).

Arterial stiffness assessed as aPWV is increased in patients with type 1 diabetes without clinical cardiovascular disease, independently of classical cardiovascular risk factors. In men with type 1 diabetes, low-grade inflammation is independently associated with arterial stiffness.

Insulin resistance, as measured by surrogate markers, is associated with lower response to hepatitis C virus (HCV) therapy and may improve with HCV eradication. We prospectively evaluated the impact of directly measured insulin resistance and abnormal glucose metabolism on achieving sustained virologic response (SVR) with HCV therapy and assessed whether SVR results in improved insulin sensitivity and fasting glucose.

A total of 50 noncirrhotic, nondiabetic, HCV-infected patients (27 untreated, 23 treated with pegylated interferon/ribavirin, nonrandomized) underwent clinical and histologic evaluation and 75-g oral glucose tolerance test. Insulin sensitivity was assessed directly with insulin suppression test by measuring steady-state plasma glucose (SSPG) concentration during a 240-min infusion of octreotide, glucose, and insulin. Of the subjects, 43 had at least one follow-up evaluation.

Patient characteristics were median age 48, 57% male, and 52% white. SVR was achieved in 61% (14 of 23) of treated subjects. SVR was independently associated with HCV genotypes 2 and 3 (odds ratio 8.8 [95% CI 1.2–61.7]) but was not strongly associated with insulin sensitivity. When controlling for elapsed time between measurements, being on interferon, and BMI, SSPG decreased by 36 mg/dL (–88 to 16) in those with SVR and decreased by 28 mg/dL (–93 to 38) in those without SVR, compared with the untreated group. BMI (coefficient 9.1 per 5 units; 95% CI 5.3–12.9) and interferon use (coefficient 56; 95% CI 6.8–105) were associated with SSPG.

Insulin resistance does not appear to be strongly associated with SVR. HCV therapy may improve insulin resistance regardless of virologic response; however, BMI and interferon use were clearly associated with insulin resistance.

The study randomly assigned 67 patients with type 1 diabetes to receive 24-month benfotiamine (300 mg/day) or placebo supplementation. Peripheral nerve function and levels of soluble inflammatory variables were assessed at baseline and at 24 months.

Fifty-nine patients completed the study. Marked increases in whole-blood concentrations of thiamine and thiamine diphosphate were found in the benfotiamine group (both P < 0.001 vs. placebo). However, no significant differences in changes in peripheral nerve function or soluble inflammatory biomarkers were observed between the groups.

Our findings suggest that high-dose benfotiamine (300 mg/day) supplementation over 24 months has no significant effects upon peripheral nerve function or soluble markers of inflammation in patients with type 1 diabetes.

To examine the association between early retinal arteriolar abnormalities and diabetic peripheral neuropathy (DPN).

Data from 608 people (aged 40–80 years) with diabetes from the population-based Singapore Malay Eye Study were analyzed. Participants underwent binocular two-field digital retinal photography and quantitative sensory testing. DPN was defined as an abnormal response to a monofilament or neurothesiometer test. Quantitative changes of retinal vascular caliber and arteriolar bifurcation geometry were measured using a computer-based program. Qualitative retinal signs of retinopathy and retinal arteriolar wall signs were graded by standardized methods.

DPN was present in 155 people (25.5%). After adjusting for age, sex, diabetes duration, HbA_1c, cardiovascular risk factors, antihypertensive medication use, and peripheral arterial disease, people with suboptimal arteriolar caliber (odds ratio 1.94 [95% CI 1.22–3.10]), larger arteriolar branching coefficient (1.58 [1.03–2.42]), diabetic retinopathy (1.82 [1.20–2.75]), and focal arteriolar narrowing (2.92 [1.48–5.76]) were more likely to have DPN. Participants with a greater number of retinal microvascular signs were more likely to have DPN than those without retinal changes (6.11 [2.11–17.71] for two or more signs and 3.47 [1.18–10.21] for one sign compared with none).

Individuals with diabetes with early retinal arteriolar abnormalities are more likely to have DPN, independent of hyperglycemia and major vascular risk factors. These data support the hypothesis that early microvascular dysfunction, evident in the retina, is an independent risk factor for DPN.

Midbrain dopamine (DA) neurons, which are involved with reward and motivation, are modulated by hormones that regulate food intake (insulin, leptin, and acyl ghrelin [AG]). We hypothesized that these hormones are associated with deficits in DA signaling in obesity.

We assessed the relationships between fasting levels of insulin and leptin, and AG, BMI, and insulin sensitivity index (S_I) with the availability of central DA type 2 receptor (D2R). We measured D2R availability using positron emission tomography and [¹⁸F]fallypride (radioligand that competes with endogenous DA) in lean (n = 8) and obese (n = 14) females. Fasting hormones were collected prior to scanning and S_I was determined by modified oral glucose tolerance test.

Parametric image analyses revealed associations between each metabolic measure and D2R. The most extensive findings were negative associations of AG with clusters involving the striatum and inferior temporal cortices. Regional regression analyses also found extensive negative relationships between AG and D2R in the caudate, putamen, ventral striatum (VS), amygdala, and temporal lobes. S_I was negatively associated with D2R in the VS, while insulin was not. In the caudate, BMI and leptin were positively associated with D2R availability. The direction of associations of leptin and AG with D2R availability are consistent with their opposite effects on DA levels (decreasing and increasing, respectively). After adjusting for BMI, AG maintained a significant relationship in the VS. We hypothesize that the increased D2R availability in obese subjects reflects relatively reduced DA levels competing with the radioligand.

Our findings provide evidence for an association between the neuroendocrine hormones and DA brain signaling in obese females.

Megalin, an endocytic receptor in proximal tubule cells, is involved in the mechanisms of albuminuria in diabetic nephropathy (DN). To develop efficient novel biomarkers associated with the pathogenesis of DN, we investigated urinary megalin excretion in type 2 diabetes.

Sandwich enzyme-linked immunosorbent assay systems were established with monoclonal antibodies against the NH₂ (amino [A]-megalin assay) and COOH (C-megalin assay) termini of megalin to analyze urinary forms of megalin in 68 patients with type 2 diabetes.

The A-megalin assay mainly detected a megalin ectodomain form in the soluble urinary fraction, whereas the C-megalin assay identified a full-length form in both soluble and insoluble fractions. Urinary C-megalin levels were significantly high in patients with normoalbuminuria, were elevated in line with increased albuminuria, and showed a better association with estimated glomerular filtration rate (eGFR) (<60 mL/min/1.73 m²) than did urinary albumin. In contrast, urinary A-megalin levels were increased in patients with normo- and microalbuminuria but not in those with macroalbuminuria. Urinary C-megalin levels were also positively associated with plasma inorganic phosphate and negatively with hemoglobin levels in those showing no features of bleeding and not taking vitamin D analogs, phosphate binders, or erythropoiesis-stimulating agents.

Urinary full-length megalin excretion as measured by the C-megalin assay is well associated with reduced eGFR and linked to the severity of DN, phosphate dysregulation, and anemia, whereas urinary excretion of megalin ectodomain as measured by the A-megalin assay may be associated with distinctive mechanisms of earlier DN in type 2 diabetes.

To determine the mechanism by which the bile acid sequestrant colesevelam improves glycemic control.

We performed a frequently sampled intravenous glucose tolerance test (FSIGT) with minimal model analysis and a meal tolerance test (MTT) in 20 subjects with impaired fasting glucose (11 men, 9 women; mean age 60.7 ± 1.9 years, BMI 29.4 ± 0.9 kg/m²) in a single-blind study after 2 weeks of placebo treatment and 8 weeks of colesevelam 3.75 g daily. From these tests, insulin sensitivity, β-cell function, and glucose tolerance were determined, along with gastrointestinal peptide levels during the MTT.

Fasting plasma glucose and HbA_1c decreased with colesevelam (from 5.9 ± 0.1 to 5.7 ± 0.1 mmol/L, P < 0.05, and from 5.86 ± 0.06 to 5.76 ± 0.06%, P = 0.01, respectively), but fasting insulin did not change. Colesevelam had no effect on any FSIGT measures. In contrast, the MTT incremental area under the curve (iAUC) for both glucose (from 249.3 ± 28.5 to 198.8 ± 23.6 mmol/L ⋅ min, P < 0.01) and insulin (from 20,130 [13,542–35,292] to 13,086 [9,804–21,138] pmol/L ⋅ min, P < 0.05) decreased with colesevelam. However, the ratio of iAUC insulin to iAUC glucose was not changed. iAUC for cholecystokinin (CCK) increased (from 43.2 [0–130.1] to 127.1 [47.2–295.2] pmol/L ⋅ min, P < 0.01), while iAUC for fibroblast growth factor 19 decreased (from 11,185 [1,346–17,661] to 2,093 [673–6,707] pg/mL ⋅ min, P < 0.01) with colesevelam. However, iAUC for glucagon, glucose-dependent insulinotropic peptide, and glucagon-like peptide 1 did not change.

Colesevelam improves oral but not intravenous glucose tolerance without changing insulin sensitivity, β-cell function, or incretins. This effect may be at least partially explained by the colesevelam-induced increase in CCK.

Hypoglycemia is associated with failure to show cardiovascular benefit and increased mortality of intensive glycemic control in randomized clinical trials. This retrospective cohort study aimed to examine the impact of hypoglycemia on vascular events in clinical practice.

Patients with type 2 diabetes were identified by ICD-9-CM codes (250.xx except for 250.x1 and 250.x3) between 1 January 2004 and 1 September 2010 from the Veterans Integrated Service Network 16. Index date was defined as the first date of new antihyperglycemic medications (index treatment). Patients with 1-year preindex records of hypoglycemia, cardiovascular, and microvascular diseases were excluded. The hypoglycemia group was identified by ICD-9-CM codes (250.8, 251.0, 251.1, and 251.2) within the index treatment period. A propensity score–matched group was used as control subjects. Cardiovascular events, microvascular complications, and all-cause death were compared using Kaplan-Meier analysis and Cox proportional hazards regression model.

Among the unmatched sample (N = 44,261), the hypoglycemia incidence rate was 3.57/100 patient-years. The matched sample (hypoglycemia group: n = 761; control group: n = 761) had a median follow-up of 3.93 years, mean age of 62.6 ± 11.0 years, and preindex HbA_1c of 10.69 ± 2.61%. The 1-year change in HbA_1c was similar (hypoglycemia group –0.51 vs. control group –0.32%, P = 0.7244). The hypoglycemia group had significantly higher risks of cardiovascular events (hazard ratio 2.00 [95% CI 1.63–2.44]) and microvascular complications (1.76 [1.46–2.11]) but no statistical mortality difference. Patients with at least two hypoglycemic episodes were at higher risks of vascular events than those with one episode (1.53 [1.10–1.66]).

Hypoglycemia is associated with higher risks of incident vascular events. Patients with hypoglycemia should be monitored closely for vascular events.

Low vitamin D status is common among healthy black and white adolescents residing at southern U.S. latitudes with a year-round sunny climate. Thus we aimed to study the relationships between circulating 25-hydroxyvitamin D [25(OH)D] and cardiometabolic risk factors in this population.

25(OH)D concentrations were measured with liquid chromatography tandem mass spectroscopy in 701 girls and boys (14–18 years old, 54% blacks, 49% females). Cardiometabolic risk was indexed by adipokines, inflammatory markers, fasting glucose, homeostatic model assessment-insulin resistance (HOMA-IR), lipid profile, and blood pressure (BP).

Controlling for age, sex, race, sexual maturation, season, physical activity, and percent body fat, 25(OH)D concentrations were significantly correlated with adiponectin (r = 0.06, P = 0.05), leptin (r = –0.32, P < 0.01), fibrinogen (r = –0.05, P = 0.03), glucose (r = –0.16, P = 0.02), HOMA-IR (r = –0.17, P < 0.01), HDL cholesterol (r = 0.14, P = 0.02), systolic BP (r = –0.10, P = 0.02), and diastolic BP (r = –0.21, P < 0.01). When 25(OH)D concentrations were stratified into increasing tertiles, there were significant linear upward trends for adiponectin (P = 0.01) and HDL cholesterol (P = 0.04), but significant linear down trends for glucose (P < 0.01), HOMA-IR (P < 0.01), and systolic BP (P < 0.01), after adjusting for the above covariates.

Circulating 25(OH)D concentrations are associated with various adverse cardiometabolic risk factors, independent of adiposity. Clinical trials addressing the effects of vitamin D supplementation on cardiometabolic risk are warranted in adolescents irrespective of their geographical regions.

The effects of longitudinal changes in the visceral fat area (VFA), and other anthropometric indices, on the risk factors of metabolic syndrome were not studied. We calculated the changes in metabolic risk factors in relation to changes in certain anthropometric indices in a large-scale study of Japanese men.

The subjects were 1,106 men participating in the Hitachi Health Study who received a computed tomography examination in both 2004 and 2007. VFA, subcutaneous fat area (SFA), and waist circumference were measured using the computed tomography. We examined how longitudinal changes in each anthropometric index over a 3-year period influenced the value of each metabolic risk factor.

Changes () over a 3-year period in body weight, SFA, and waist circumference strongly correlated, while the changes in body weight and VFA were weakly correlated. Changes in the VFA were associated with changes in metabolic risk factors, especially changes in triglyceride and HDL; we found these changes to be independent of the body weight and waist circumference.

Change in body weight is not a precise surrogate marker of VFA, and repeated VFA measurements over time are useful. Adopting a lifestyle that does not increase the VFA is important in preventing metabolic syndrome.

We evaluated whether cardiometabolic risk profiles differ for subjects identified as having prediabetes by A1C, fasting glucose (FPG), or 2-h postchallenge glucose (2-PG) criteria.

Atherosclerosis risk factors, oral glucose tolerance test, and ultrasound measurement of carotid intima–media thickness (IMT) were analyzed in 780 nondiabetic individuals.

Poor agreement existed for A1C and FPG criteria for identification of subjects with prediabetes ( coefficient = 0.332). No differences in cardiometabolic risk profiles were observed among the three groups of individuals with prediabetes by A1C only, FPG only, and both A1C and FPG. Poor agreement also existed for A1C and 2-PG criteria for identification of individuals with prediabetes ( coefficient = 0.299). No significant differences in cardiometabolic risk factors were observed between IGT-only and individuals with prediabetes by A1C and 2-PG. Compared with subjects with prediabetes identified by A1C only, IGT-only individuals exhibited a worse cardiometabolic risk profile, with significantly higher systolic blood pressure, pulse pressure, 2-h postchallenge insulin, triglycerides, high-sensitivity C-reactive protein, and carotid IMT, and lower HDL cholesterol levels and insulin sensitivity.

These results suggest that considerable discordance between A1C, FPG, and 2-PG exists for the identification of individuals with prediabetes and that the cardiometabolic risk profile of these individuals varies by metabolic parameter, with 2-PG showing the stronger association with cardiometabolic risk factors and subclinical atherosclerosis than FPG or A1C.

To determine the best lipid variable to predict coronary heart disease (CHD) in Japanese patients with type 2 diabetes.

Eligible Japanese men and women (1,771) aged 40–70 years with type 2 diabetes from 59 institutes nationwide were followed for a planned 8-year period. The performance of eight conventional lipid variables, i.e., total cholesterol (TC), LDL-cholesterol (LDLC), HDL-cholesterol (HDLC), triglycerides (TGs), non-HDLC, TC/HDLC ratio, LDLC/HDLC ratio, and TG/HDLC ratio, as predictors of incident CHD were evaluated by four methods: hazard ratio (HR) per one SD increment by multivariate Cox analysis, ² likelihood ratio test, area under the receiver operating characteristic curve (AUC), and tertile analysis.

Although all variables significantly predicted CHD events in men, non-HDLC (HR per one SD 1.78 [95% CI 1.43–2.21]; AUC 0.726) and TC/HDLC (HR 1.63 [1.36–1.95]; AUC 0.718) had the better predictive performances among the variables, including LDLC. In women, TGs (log-transformed; HR 1.72 [1.21–2.43]; AUC 0.708) were the best predictor according to results of tertile analysis (HR of the top tertile versus the bottom tertile 4.31 [1.53–12.16]). The associations with incident CHD were linear and continuous.

For Japanese diabetic men, non-HDLC and TC/HDLC were the best predictors, whereas TGs were most predictive for women. These findings, which included prominent sex differences, should be considered among clinical approaches to risk reduction among East Asians with diabetes.

Optimal vitamin D levels are associated with reduced cardiovascular and all-cause mortality. We investigated whether optimal 25-hydroxyvitamin D (25[OH]D) is protective in individuals with the metabolic syndrome.

The Ludwigshafen Risk and Cardiovascular Health (LURIC) study is a cohort study of subjects referred for coronary angiography between 1997 and 2000, from which 1,801 with the metabolic syndrome were investigated. Mortality was tracked for a median of 7.7 years. Multivariable survival analysis was used to estimate the association between 25(OH)D levels and mortality.

Most subjects (92%) had suboptimal levels of 25(OH)D (<75 nmol/L), with 22.2% being severely deficient (<25 nmol/L). During follow-up, 462 deaths were recorded, 267 (57.8%) of which were cardiovascular in origin. After full adjustment, including the metabolic syndrome components, those with optimal 25(OH)D levels showed a substantial reduction in all-cause (hazard ratio [HR] 0.25 [95% CI 0.13–0.46]) and cardiovascular disease mortality (0.33 [0.16–0.66]) compared with those with severe vitamin D deficiency. For specific cardiovascular disease mortality, there was a strong reduction for sudden death (0.15 [0.04–0.63]) and congestive heart failure (0.24 [0.06–1.04]), but not for myocardial infarction. The reduction in mortality was dose-dependent for each of these causes.

Optimal 25(OH)D levels substantially lowered all-cause and cardiovascular disease mortality in subjects with the metabolic syndrome. These observations call for interventional studies that test whether vitamin D supplementation provides a useful adjunct in reducing mortality in these subjects.

Glycemic control in type 2 diabetes generally worsens over time, requiring intensification of therapy. The Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) trial provided the opportunity to observe glycemic control in a real-world setting. We assessed the adequacy of metformin, sulfonylureas, and insulin to maintain glycemic control and their effects on weight.

Diabetes control was measured at baseline and yearly for a median of 5 years in the 4,900 patients from the nonintervention arm of this study allocated to placebo.

Median HbA_1c was 6.9% at baseline and increased by an average of 0.22% over 5 years (P < 0.001). Median weight was 86.3 kg at baseline and decreased by 0.4 kg over 5 years (P = 0.002). Baseline therapy was lifestyle measures only in 27%, oral agents without insulin in 59%, and insulin in 14% (7% also taking oral agents). Over 5 years, insulin use increased to 32% (21% also taking oral agents). Use of oral agents remained similar at 56%. Only 2% of patients at baseline and 4% after 5 years were taking oral agents other than metformin or sulfonylureas. Initiation of insulin therapy in 855 patients produced a sustained reduction of HbA_1c from a median of 8.2 to 7.7%, with a weight gain of 4.6 kg over 5 years.

With intensification of traditional therapies, glycemic control deteriorated very little over 5 years in a large cohort of type 2 diabetes. However, the requirement for insulin therapy doubled, at the expense of significant weight gain and risk of hypoglycemia.

MEDLINE, EMBASE, and PsycINFO databases were searched for articles published up to January 2012. Cross-sectional and cohort studies that reported an association between the two conditions in adults were included. Data on prevalence, incidence, unadjusted or adjusted odds ratio (OR), and 95% CI were extracted or provided by the authors. The pooled OR was calculated separately for cross-sectional and cohort studies using random-effects models. The I² statistic was used to assess heterogeneity.

The search yielded 29 cross-sectional studies (n = 155,333): 27 studies reported unadjusted OR with a pooled estimate of 1.42 (95% CI 1.28–1.57; I² = 55.1%); 11 studies reported adjusted OR with depression as the outcome (1.27 [1.07–1.57]; I² = 60.9%), and 12 studies reported adjusted OR with MetS as the outcome (1.34 [1.18–1.51]; I² = 0%). Eleven cohort studies were found (2 studies reported both directions): 9 studies (n = 26,936 with 2,316 new-onset depression case subjects) reported adjusted OR with depression as the outcome (1.49 [1.19–1.87]; I² = 56.8%), 4 studies (n = 3,834 with 350 MetS case subjects) reported adjusted OR with MetS as the outcome (1.52 [1.20–1.91]; I² = 0%).

Our results indicate a bidirectional association between depression and MetS. These results support early detection and management of depression among patients with MetS and vice versa.