This prospective multicenter study involved 19 Spanish hospitals. Noncritically ill patients who were prescribed TPN were included prospectively, and data were collected on demographic, clinical, and laboratory variables as well as on in-hospital mortality.

The study included 605 patients (mean age 63.2 ± 15.7 years). The daily mean TPN values were 1.630 ± 323 kcal, 3.2 ± 0.7 g carbohydrates/kg, 1.26 ± 0.3 g amino acids/kg, and 0.9 ± 0.2 g lipids/kg. Multiple logistic regression analysis showed that the patients who had mean blood glucose levels >180 mg/dL during the TPN infusion had a risk of mortality that was 5.6 times greater than those with mean blood glucose levels <140 mg/dL (95% CI 1.47–21.4 mg/dL) after adjusting for age, sex, nutritional state, presence of diabetes or hyperglycemia before starting TPN, diagnosis, prior comorbidity, carbohydrates infused, use of steroid therapy, SD of blood glucose level, insulin units supplied, infectious complications, albumin, C-reactive protein, and HbA_1c levels.

Hyperglycemia (mean blood glucose level >180 mg/dL) in noncritically ill patients who receive TPN is associated with a higher risk of in-hospital mortality.

Patients (n = 426) were randomized 1:1 to sitagliptin (50 mg every day [q.d.] for moderate renal insufficiency and 25 mg q.d. for severe renal insufficiency) or glipizide (2.5 mg q.d., adjusted based on glycemic control to a 10-mg twice a day maximum dose). Randomization was stratified by: 1) renal status (moderate or severe renal insufficiency); 2) history of cardiovascular disease; and 3) history of heart failure.

At week 54, treatment with sitagliptin was noninferior to treatment with glipizide in A1C change from baseline (–0.8 vs. –0.6%; between-group difference –0.11%; 95% CI –0.29 to 0.06) because the upper bound of the 95% CI was less than the prespecified noninferiority margin of 0.4%. There was a lower incidence of symptomatic hypoglycemia adverse events (AEs) with sitagliptin versus glipizide (6.2 and 17.0%, respectively; P = 0.001) and a decrease in body weight with sitagliptin (–0.6 kg) versus an increase (1.2 kg) with glipizide (difference, –1.8 kg; P < 0.001). The incidence of gastrointestinal AEs was low with both treatments.

In patients with T2DM and chronic renal insufficiency, sitagliptin and glipizide provided similar A1C-lowering efficacy. Sitagliptin was generally well-tolerated, with a lower risk of hypoglycemia and weight loss versus weight gain, relative to glipizide.

Serum ZAG (determined with ELISA) was compared with various parameters related to insulin resistance in subjects with normal glucose tolerance, impaired glucose tolerance (IGT), and newly diagnosed type 2 diabetes mellitus (T2DM), and in women with or without polycystic ovary syndrome (PCOS). Euglycemic-hyperinsulinemic clamps were performed in healthy and PCOS women. Real-time RT-PCR and Western blotting were used to assess mRNA and protein expression of ZAG. The effect of a glucagon-like peptide-1 agonist on ZAG was studied in a 12-week liraglutide treatment trial.

Circulating ZAG was lower in patients with IGT and newly diagnosed T2DM than in controls. Circulating ZAG correlated positively with HDL cholesterol and adiponectin, and correlated inversely with BMI, waist-to-hip ratio, body fat percentage, triglycerides, fasting blood glucose, fasting insulin, HbA_1c, and homeostasis model assessment of insulin resistance (HOMA-IR). On multivariate analysis, ZAG was independently associated with BMI, HOMA-IR, and adiponectin. ZAG mRNA and protein were decreased in adipose tissue of T2DM patients. Moreover, circulating ZAG levels were lower in women with PCOS than in women with high insulin sensitivity. Liraglutide treatment for 12 weeks significantly increased circulating ZAG levels.

We conclude that ZAG may be an adipokine associated with insulin resistance.

We identified and followed (median 20 months) 254 women with singleton pregnancies receiving postdelivery medical care at a single institution.

Study subjects were 28.3 ± 4.7 years of age (mean ± SD), with a diabetes duration of 12.0 ± 7.7 years. Mean A1C before conception was 6.9 ± 1.4%, and preconception weight and BMI were 64.4 ± 10.0 kg and 23.9 ± 3.3 kg/m², respectively. Mean A1C decreased during pregnancy, reaching 5.7 ± 0.8% in the third trimester. We observed a mean weight gain of 14.4 ± 6.5 kg during pregnancy. Within 6 months after delivery, A1C increased by 0.8% (P < 0.0001) compared with the last trimester, and body weight and BMI were 4.4 kg and 2.5 kg/m² higher (P < 0.0001) compared with the preconception baseline. A1C further deteriorated by 0.8% until the end of follow-up. For women in the "pregnancy planning" program (n = 117), A1C >12 months after delivery was worse compared with before conception (7.1 vs. 6.5%, P = 0.0018), whereas in women with unplanned pregnancies, it was similar to the pregestational levels (7.3 vs.7.4%, P = 0.59). Weight and BMI in the entire study group did not return to prepregnancy levels and were 2.5 kg (P = 0.0079) and 0.9 kg/m² higher (P = 0.0058).

In this clinical observation, type 1 diabetic women showed postpregnancy deterioration in glycemic control and were unable to return to prepregnancy weight. Type 1 diabetic women seem to require special attention after delivery to meet therapeutic targets.

Participants (n = 5,145; age [mean ± SD] 58.7 ± 6.8 years; BMI 35.8 ± 5.8 kg/m²) in two study arms (intensive lifestyle [ILI], diabetes support and education [DSE]) completed the Beck Depression Inventory (BDI), reported ADM use, and were assessed for CVD risk factors at baseline and annually for 4 years. Risk factor–positive status was defined as current smoking, obesity, HbA_1c >7.0% or insulin use, and blood pressure or cholesterol not at levels recommended by expert consensus panel or medicine to achieve recommended levels. Generalized estimating equations assessed within-study arm relationships of elevated BDI score (≥11) or ADM use with subsequent year CVD risk status, controlled for demographic variables, CVD history, diabetes duration, and prior CVD risk status.

Prior year elevated BDI was associated with subsequent CVD risk factor–positive status for the DSE arm (A1C [odds ratio 1.30 (95% CI 1.09–1.56)]; total cholesterol [0.80 (0.65–1.00)]; i.e., protective from high total cholesterol) and the ILI arm (HDL [1.40 (1.12–1.75)], triglyceride [1.28 (1.00–1.64)]). Prior year ADM use predicted subsequent elevated CVD risk status for the DSE arm (HDL [1.24 (1.03–1.50)], total cholesterol [1.28 (1.05–1.57)], current smoking [1.73 (1.04–2.88)]) and for the ILI arm (A1C [1.25 (1.08–1.46)], HDL [1.32 (1.11–1.58)], triglycerides [1.75 (1.43–2.14)], systolic blood pressure [1.39 (1.11–1.74)], and obesity [1.46 (1.22–2.18)]).

Aggressive monitoring of CVD risk in diabetic patients with depressive symptoms or who are treated with ADM may be warranted.

Physical activity energy expenditure (PAEE) and glucose levels (continuous glucose monitoring) were measured in 10 pregnant women with type 1 diabetes (age 33.2 years, gestation 20 weeks, BMI 27.9 kg/m², diabetes duration 16.6 years, HbA_1c 6.5% [48 mmol/mol], insulin pump duration 2.4 years) during a day at home (free-living) and during a 24-h visit incorporating controlled diet and structured physical activity with light intensity activity (three 20-min self-paced walks) and moderate intensity activity (two 50-min sessions of brisk treadmill walking). PAEE was evaluated through individually calibrated combined heart rate and movement sensing.

Free-living PAEE was comparable to that under controlled study conditions (3.8 and 5.1 kcal/kg/day, P = 0.241), with women achieving near to the recommended 30 min of moderate physical activity (median 27 min [interquartile range 14–68]). During the free-living period, more time was spent in light activity (10.3 vs. 7.2 h, P = 0.005), with less sedentary time (13.0 vs. 14.9 h, P = 0.047) and less moderate activity (27 vs. 121 min, P = 0.022). The free-living 24-h mean glucose levels by continuous glucose monitoring were significantly higher (7.7 vs. 6.0 mmol/L, P = 0.028). The effect of controlled diet and exercise persisted overnight, with significantly less time spent hyperglycemic (19 vs. 0%, P = 0.028) and less glucose variability (glucose SD 1.3 vs. 0.7 mmol/L, P = 0.022).

A controlled diet and structured physical activity program may assist women with type 1 diabetes in achieving optimal glucose control during pregnancy.

A retrospective cohort comprised the records of 58 singleton pregnancies in obese women (BMI ≥30 kg/m²) with type 2 diabetes giving birth between 2008 and 2011. Birth weight was evaluated by SD z score to adjust for gestational age and sex.

Seventeen women (29%) gained ≤5 kg, and the remaining 41 gained >5 kg. The median (range) gestational weight gains were 3.7 kg (–4.7 to 5 kg) and 12.1 kg (5.5–25.5 kg), respectively. Prepregnancy BMI was 33.5 kg/m² (30–53 kg/m²) vs. 36.8 kg/m² (30–48 kg/m²), P = 0.037, and median HbA_1c was 6.7% at first visit in both groups and decreased to 5.7 and 6.0%, P = 0.620, in late pregnancy, respectively. Gestational weight gain ≤5 kg was associated with lower birth weight z score (P = 0.008), lower rates of large-for-gestational-age (LGA) infants (12 vs. 39%, P = 0.041), delivery closer to term (268 vs. 262 days, P = 0.039), and less perinatal morbidity (35 vs. 71%, P = 0.024) compared with pregnancies with maternal weight gain >5 kg.

In this pilot study in obese women with type 2 diabetes, maternal gestational weight gain ≤5 kg was associated with a more proportionate birth weight and less perinatal morbidity.

Data for this retrospective cohort study were obtained from electronic databases of patients admitted between 1 April 2008 and 30 November 2010. Patients with one or more blood glucose values ≤50 mg/dL on point-of-care glucose testing were considered hypoglycemic. Patients treated with insulin were assumed to have insulin-associated hypoglycemia. Age-, sex-, and race-matched patients with all blood glucose values >70 mg/dL were selected as controls. The Charlson comorbidity index (CCI) was used to control for severity of illness.

There were four groups: 1) noninsulin-treated hypoglycemia (NTH) (n = 135), 2) insulin-treated hypoglycemia (ITH) (n = 961), 3) noninsulin-treated control (NTC) (n = 1,058), and 4) insulin-treated control (ITC) (n = 736). Mortality was higher in the ITH group compared with the ITC group (20.3 vs. 4.5%, P < 0.0001), with a relatively higher CCI (1.8 vs. 1.5%, P < 0.0001), but much higher in the NTH group compared with the NTC group (34.5 vs. 1.1%, P < 0.0001), with much higher CCI (2.4 vs. 1.1%, P < 0.0001). Mortality was higher in the NTH group compared with the ITH group (P < 0.0001) but lower in the NTC group compared with the ITC group (P < 0.0001). After controlling for age, sex, CCI, and admission to the intensive care unit, insulin treatment was associated with a lower mortality among the hypoglycemic patients; hazard ratio of death in the ITH group relative to the NTH group was 0.34 (95% CI 0.25–0.47, P < 0.0001).

Insulin-associated and spontaneous hypoglycemia are associated with increased mortality among hospitalized patients.

Estimates for maternity care resource activity and costs for 4,372 women, of whom 354 (8.1%) were diagnosed with GDM, were generated from data from the Atlantic Diabetes in Pregnancy (ATLANTIC DIP) database. Multivariate regression analysis was applied to explore the effects of GDM on 1) mode of delivery, 2) neonatal unit admission, and 3) maternity care cost, while controlling for a range of other demographic and clinical variables.

Women with a diagnosis of GDM had significantly higher levels of emergency caesarean section (odds ratio [OR] 1.75 [95% CI 1.08–2.81]), their infants had significantly higher levels of neonatal unit admission (3.14 [2.27–4.34]), and costs of care were 34% greater (25–43) than in women without GDM. Other variables that significantly increased costs were weight, age, primiparity, and premature delivery.

GDM plays an independent role in explaining variations in rates of emergency caesarean section, neonatal unit admission, and costs of care, placing a substantial economic burden on maternity care services. Interventions that prevent the onset of GDM have the potential to yield substantial economic and clinical benefits.

We conducted independent forward and backward translation of the validated German DSQOLS. An iterative interview study with health professionals (n = 3) and adults with type 1 diabetes (n = 8) established linguistic validity. The DSQOLS was included in three Dose Adjustment for Normal Eating (DAFNE) studies (total N = 1,071). Exploratory factor analysis (EFA) was undertaken to examine questionnaire structure. Concurrent and discriminant validity, internal consistency, and reliability were assessed.

EFA indicated a six-factor structure for the DSQOLS (social aspects, fear of hypoglycemia, dietary restrictions, physical complaints, anxiety about the future, and daily hassles). High internal consistency reliability was found for these factors and the weighted treatment satisfaction scale (α = 0.85–0.94). All subscales were moderately, positively correlated with the Audit of Diabetes-Dependent Quality-of-Life (ADDQoL) measure, demonstrating evidence of concurrent validity. Lower DSQOLS subscale scores [indicating impaired quality of life (QoL)] were associated with the presence of diabetes-related complications.

The DSQOLS captures the impact of detailed aspects of modern type 1 diabetes management (e.g., carbohydrate counting and flexible insulin dose adjustment) that are now routine in many parts of the U.K. and Ireland. The U.K. English version of the DSQOLS offers a valuable tool for assessing the impact of treatment approaches on QoL in adults with type 1 diabetes.

We examined 1,275 stable patients with diabetes mellitus undergoing elective diagnostic coronary angiography with cardiac troponin I (cTnI) levels below the diagnostic cut-off for defining myocardial infarction (MI) (<0.03 ng/mL). The relationship of subclinical myocardial necrosis (cTnI 0.009–0.029 ng/mL) with incident major adverse cardiovascular events (MACE; defined as any death, MI, or stroke) over 3 years of follow-up was examined.

Subclinical myocardial necrosis was observed in 22% of patients. A strong association was observed between the magnitude of subclinical myocardial necrosis and risk of 3-year incident MACE (hazard ratio, 1.98; 95% confidence interval, 1.48–2.65; P < 0.001) and remained statistically significant even after adjustment for traditional risk factors, high-sensitivity C-reactive protein, and creatinine clearance. Only a weak correlation was observed between the presence of subclinical myocardial necrosis and either glycemic control (r = 0.06; P = 0.044 for hemoglobin A_1c versus cTnI) or insulin resistance (r = 0.04; P = 0.094 for glucose-to-insulin ratio versus cTnI).

The presence of detectable subclinical myocardial necrosis in stable patients with diabetes mellitus is associated with heightened long-term risk for MACE, independent of traditional risk factors and glycemic control.

This study was a randomized, controlled, three-period, crossover feeding study. The study participants were 164 individuals with prehypertension or stage 1 hypertension without diabetes. Diets were administered for 6 weeks each, with a washout period between diets of 2–4 weeks. Weight was held constant throughout the study. For our primary outcome, we calculated the quantitative insulin sensitivity check index (QUICKI) using the end-of-period fasting serum glucose and insulin. QUICKI is a validated measure of insulin sensitivity. The primary analyses used generalized estimating equations.

At baseline, mean (SD) BMI was 30.2 (6.1) kg/m², and mean (SD) QUICKI was 0.35 (0.04). The UNSAT diet increased QUICKI by 0.005, more than the CARB diet (P = 0.04). PROT had no significant effect compared with CARB.

A diet that partially replaces carbohydrate with unsaturated fat may improve insulin sensitivity in a population at risk for cardiovascular disease. Given the well-recognized challenges of sustaining weight loss, our results suggest an alternative approach for improving insulin sensitivity.

Patients without known diabetes admitted for CAG were eligible. OGTT and HbA_1c were assessed 2–4 weeks after hospital discharge. The performance of HbA_1c and FPG was evaluated by using receiver operating characteristic (ROC) analysis.

Diabetes was diagnosed in 83 of 400 patients (20.8%). The area under the ROC curve was higher for FPG than for HbA_1c (0.81 vs. 0.73, P = 0.032). We proposed a screening algorithm and validated it in another 170 patients. Overall, this algorithm reduced the number of OGTTs by 71.4% (sensitivity 74.4%, specificity 100%).

FPG performed better than HbA_1c in screening for diabetes in patients undergoing CAG. A screening algorithm might help to reduce the number of OGTTs.

Glucose tolerance status was determined in 61- to 82-year-old participants of the population-based KORA F4 Study (2006–2008) (n = 1,100). Clinical DSPN was defined as the presence of bilaterally impaired foot-vibration perception and/or bilaterally impaired foot-pressure sensation. DSPN case subjects were considered unaware of their condition when answering "no" to the question, "Has a physician ever told you that you are suffering from nerve damage, neuropathy, polyneuropathy, or diabetic foot?"

Clinical DSPN was prevalent in 154 (14%) participants, 140 of whom were unaware of their disorder. At a prevalence of 23.9% (95% CI 12.6–38.8), participants with combined impaired fasting glucose and impaired glucose tolerance had the highest prevalence of DSPN. Of these, 10 of 11 (91%) were unaware of having clinical DSPN. Participants with known diabetes had an equally high prevalence of DSPN [22.0% (16.2–28.9)], with 30 of the 39 (77%) DSPN case subjects unaware of having the disorder. Among subjects with known diabetes who reported to have had their feet examined by a physician, 18 of 25 (72%) clinical DSPN case subjects emerged unaware of having DSPN.

Our findings showed a high prevalence of unawareness of having clinical DSPN among the prediabetic and diabetic groups and an insufficient frequency of professional foot examinations, suggesting inadequate attention to diabetic foot prevention practice.

This retrospective cohort study included 584,587 encounters for 27,225 patients with diabetes and elevated A1C, blood pressure, and/or LDL cholesterol monitored for at least 2 years. Encounters occurred at primary care practices affiliated with two teaching hospitals in eastern Massachusetts.

Of the encounters documented, 83% were with PCPs, 13% were with covering physicians, and 5% were with midlevel providers. In multivariable analysis, the odds of medication intensification were 49% (P < 0.0001) and 26% (P < 0.0001) higher for PCPs than for covering physicians and midlevel providers, respectively, whereas the odds of lifestyle counseling were 91% (P < 0.0001) and 21% (P = 0.0015) higher. During visits with acute complaints, covering physicians were even less likely, by a further 52% (P < 0.0001), to intensify medications, and midlevel providers were even less likely, by a further 41% (P < 0.0001), to provide lifestyle counseling. Compared with PCPs, the hazard ratios for time to the next encounter after a visit without acute complaints were 1.11 for covering physicians and 1.19 for midlevel providers (P < 0.0001 for both).

PCPs provide better care through higher rates of medication intensification and lifestyle counseling. Covering physicians and midlevel providers may enable more frequent encounters when PCP resources are constrained.

Fracture-related hospitalization was defined using International Classification of Diseases, 9th revision, codes (733.1–733.19, 733.93–733.98, or 800–829). We calculated the incidence rate of fracture-related hospitalization by age and used Cox proportional hazards models to investigate the association of diabetes with risk of fracture after adjustment for demographic, lifestyle, and behavioral risk factors.

There were 1,078 incident fracture-related hospitalizations among 15,140 participants during a median of 20 years of follow-up. The overall incidence rate was 4.0 per 1,000 person-years (95% confidence interval [CI], 3.8–4.3). Diagnosed diabetes was significantly and independently associated with an increased risk of fracture (adjusted hazard ratio [HR], 1.74; 95% CI, 1.42–2.14). There also was a significantly increased risk of fracture among persons with diagnosed diabetes who were treated with insulin (HR, 1.87; 95% CI, 1.15–3.05) and among persons with diagnosed diabetes with hemoglobin A_1c (HbA_1c) ≥8% (1.63; 1.09–2.44) compared with those with HbA_1c <8%. Undiagnosed diabetes was not significantly associated with risk of fracture (HR, 1.12; 95% CI, 0.82–1.53).

This study supports recommendations from the American Diabetes Association for assessment of fracture risk and implementation of prevention strategies in persons with type 2 diabetes, particularly those persons with poor glucose control.

In 2001, 68,376 Nurses’ Health Study II participants answered questions on physical, sexual, and psychological intimate partner violence in adulthood (age ≥18 years) and reported the years in which any abuse occurred. We used Cox proportional hazards models to estimate the associations between intimate partner violence exposures and incidence of type 2 diabetes from 2001 to 2007. We also estimated effects of duration and time since intimate partner violence on type 2 diabetes incidence.

Of 68,376 respondents, 64,732 met inclusion criteria at the 2001 baseline; of these, 23% reported lifetime physical intimate partner violence, 11% reported lifetime sexual intimate partner violence, and 8% reported moderate and <2% reported severe psychological intimate partner violence. Hazard ratios (HRs) and 95% CIs for type 2 diabetes, adjusted for potential confounders, were 1.18 (1.00–1.39) and 1.08 (0.86–1.35) for more than one lifetime episode of physical and sexual intimate partner violence, respectively, and 1.78 (1.21–2.61) for severe psychological abuse. Addition of updated BMI and other diabetes risk factors reduced the physical intimate partner violence HR to 1.12 (0.94–1.33) and the psychological intimate partner violence HR to 1.61 (1.09–2.38).

Physical intimate partner violence is modestly associated with incidence of type 2 diabetes in this population. Severe psychological violence may substantially increase type 2 diabetes risk.

This prospective study was based on 2,641 middle-aged men 42–60 years of age at baseline. Impaired FPG level (≥5.6 mmol/L) among nondiabetic subjects (501 men) was defined according to the established guidelines, and the group with type 2 diabetes included subjects (159 men) who were treated with oral hypoglycemic agents, insulin therapy, and/or diet.

During the 19-year follow-up, a total of 190 SCDs occurred. The relative risk (RR) for SCD was 1.51-fold (95% CI 1.07–2.14, P = 0.020) for nondiabetic men with impaired FPG and 2.86-fold (1.87–4.38, P < 0.001) for men with type 2 diabetes as compared with men with normal FPG levels, after adjustment for age, BMI, systolic blood pressure, serum LDL cholesterol, smoking, prevalent coronary heart disease (CHD), and family history of CHD. The respective RRs for out-of-hospital SCDs (157 deaths) were 1.79-fold (1.24–2.58, P = 0.001) for nondiabetic men with impaired FPG and 2.26-fold (1.34–3.77, P < 0.001) for men with type 2 diabetes. Impaired FPG and type 2 diabetes were associated with the risk of all-cause death. As a continuous variable, a 1 mmol/L increment in FPG was related to an increase of 10% in the risk of SCD (1.10 [1.04–1.20], P = 0.001).

Impaired FPG and type 2 diabetes represent risk factors for SCD.

We estimated the cumulative 5-year cost of caring for people with diabetes using a province-wide cohort of adults with diabetes as of 1 May 2004. Costs included physician visits, hospitalizations, ambulatory care (emergency room visits, day surgery, and day medicine), and drug costs for people >65 years of age. Using linked laboratory and administrative clinical and costing data, we determined the association between baseline glycemic control (HbA_1c), proteinuria, and kidney function (eGFR) and 5-year costs, controlling for age, socioeconomic status, duration of diabetes, and comorbid illness.

We identified 138,662 adults with diabetes. The mean 5-year cost of diabetes in the overall cohort was $26,978 per patient, excluding drug costs. The mean 5-year cost for the subset of people >65 years of age, including drug costs, was $44,511 (Canadian dollars). Cost increased with worsening kidney function, presence of proteinuria, and suboptimal glycemic control (HbA_1c >7.9%). Increasing age, Aboriginal status, socioeconomic status, duration of diabetes, and comorbid illness were also associated with increasing cost.

The cost of caring for people with diabetes is substantial and is associated with suboptimal glycemic control, abnormal kidney function, and proteinuria. Future studies should assess if improvements in the management of diabetes, assessed with laboratory-derived measurements, result in cost reductions.

Clinical and immunogenetic markers of autoimmune diabetes were studied in 136 individuals with DSD and compared with 194 age- and sex-matched individuals with type 1 diabetes, 222 with DS, and 671 healthy controls. HLA class II was analyzed by sequence-specific primed PCR. Islet autoantibodies were measured by radioimmunoassay.

Age at onset of diabetes was biphasic, with 22% of DS children diagnosed before 2 years of age, compared with only 4% in this age-group with type 1 diabetes in the general population (P < 0.0001). The frequency of the highest-risk type 1 diabetes–associated HLA genotype, DR3-DQ2/DR4-DQ8, was decreased in both early- and later-onset DSD compared with age-matched children with type 1 diabetes (P < 0.0001), although HLA DR3-DQ2 genotypes were increased (P = 0.004). Antibodies to GAD were observed in all five samples tested from children diagnosed at ≤2 years of age, and persistent islet autoantibodies were detected in 72% of DSD cases. Thyroid and celiac disease were diagnosed in 74 and 14%, respectively, of the DSD cohort.

Early-onset diabetes in children with DS is unlikely to be etiologically different from autoimmune diabetes occurring in older DS children. Overall, these studies demonstrate more extreme autoimmunity in DSD typified by early-onset diabetes with multiple autoimmunity, persistent islet autoantibodies, and decreased HLA-mediated susceptibility.

Using a prospective study with 12 rural Japanese general populations (n = 3,641, mean age, 53.7 years; 33.5% men), we examined the associations between diabetes and the risk of all-cause death, CVD death, and cancer death. We also examined the effects of BMI and age on such associations.

During an average duration of 10.2 years (37,278 person-years), 240 deaths occurred (54 deaths from CVD, 101 from cancer, and 85 from other causes). Cox regression analysis showed leanness (defined as the lowest quartile of entire BMI; mean, 19.5 kg/m²), but not obesity (BMI ≥25 kg/m²), and diabetes were independently associated with an increased risk of all-cause death (hazard ratio [HR] 1.70 and 1.65, respectively; both P < 0.01.). Stratification with cause-specific deaths showed that leanness and obesity were associated with CVD death (HR 3.77 and 2.94, respectively), whereas diabetes was associated with cancer death (HR 1.87; all P < 0.05). The increased risk of all-cause death in diabetes was substantially higher in lean subjects aged <65 years (HR 3.4) or those aged ≥65 years (HR 4.2), whereas the risk in obese diabetes patients was significant only in subjects aged <65 years (HR 2.32; all P < 0.05).

Among the Japanese general population, diabetes confers an increased risk of all-cause death. Particular attention must be paid to the pronounced high mortality in diabetes accompanied with leanness, regardless of age.

We analyzed pooled data from two clinical trials on 1,748 Japanese type 2 diabetic patients without diabetes complications other than mild diabetic retinopathy with a median follow-up of 7.2 years. End points were coronary heart disease (CHD), stroke, noncardiovascular mortality, overt nephropathy defined by persistent proteinuria, and progression of retinopathy. We fit a multistate Cox regression model to derive an algorithm for prediction. The predictive accuracy of the calculated 5-year risks was cross-validated.

Sex, age, HbA_1c, years after diagnosis, BMI, systolic blood pressure, non-HDL cholesterol, albumin-to-creatinine ratio, atrial fibrillation, current smoker, and leisure-time physical activity were risk factors for macro- and microvascular complications and were incorporated into the risk engine. The observed-to-predicted (O/P) ratios for each event were between 0.93 and 1.08, and Hosmer-Lemeshow tests showed no significant deviations between observed and predicted events. In contrast, the UK Prospective Diabetes Study (UKPDS) risk engine overestimated CHD risk (O/P ratios: 0.30 for CHD and 0.72 for stroke). C statistics in our Japanese patients were high for CHD, noncardiovascular mortality, and overt nephropathy (0.725, 0.696, and 0.767) but moderate for stroke and progression of retinopathy (0.636 and 0.614). By combining macro- and microvascular risks, the classification of low- and high-risk patients was improved by a net reclassification improvement of 5.7% (P = 0.02).

The risk engine accurately predicts macro- and microvascular complications and would provide helpful information in risk classification and health economic simulations.

Using data from the Kaiser Permanente Diabetes Study of Northern California (DISTANCE) survey, we estimated the association between neighborhood deprivation and two measures of BMI change over 3 years: 1) a continuous measure and 2) a categorical measure of clinically substantive BMI loss or gain (≥7% of baseline BMI) versus stable BMI. The sample included 13,609 adults.

On average, there was little change in BMI (–0.12, SD 3.07); 17.0 and 16.1% had clinically substantive BMI loss or gain, respectively, at follow-up. There was a positive association between neighborhood deprivation and BMI change for adults in the most versus least-deprived quartile of neighborhood deprivation (β = 0.22, P = 0.02) in adjusted models. In addition, relative to the least-deprived quartile (Q1), adults in more-deprived quartiles of neighborhood deprivation were more likely to experience either substantive BMI loss (Q2 relative risk ratio 1.19, 95% CI 1.00–1.41; Q3 1.20, 1.02–1.42; Q4 1.30, 1.08–1.55) or gain (Q2 1.25, 1.04–1.49; Q3 1.24, 1.04–1.49; Q4 1.45, 1.20–1.75).

Greater neighborhood deprivation was positively associated with BMI change among adults with diabetes as well as with clinically substantive BMI loss or gain. Findings stress the importance of allowing for simultaneous associations with both gain and loss in future longitudinal studies of neighborhood deprivation and weight change, which may be particularly true for studies of patients with diabetes for whom both weight loss and gain have health implications.

We used data from the Healthcare Cost and Utilization Project State Inpatient Databases for 23 states of the United States with available race/ethnicity data for 2008 to examine age-adjusted and race-adjusted rates of GDM by state. We used multilevel analysis to examine factors that explain the variability in GDM between states.

Age-adjusted and race-adjusted GDM rates (per 100 deliveries) varied widely between states, ranging from 3.47 in Utah to 7.15 in Rhode Island. Eighty-six percent of the variability in GDM between states was explained as follows: 14.7% by age; 11.8% by race/ethnicity; 5.9% by insurance; and 2.9% by interaction between race/ethnicity and insurance at the individual level; 17.6% by hospital level factors; 27.4% by the proportion of obese women in the state; 4.3% by the proportion of Hispanic women aged 15–44 years in the state; and 1.5% by the proportion of white non-Hispanic women aged 15–44 years in the state.

Our results suggest that GDM rates differ by state, with this variation attributable to differences in obesity at the population level (or "at the state level"), age, race/ethnicity, hospital, and insurance.

We examined electronic health records for 15,683 persons of non-Hispanic white (NHW), Asian (Asian Indian, Chinese, and Filipino), Hispanic, and non-Hispanic black (NHB) race/ethnicity with type 2 diabetes and no prior history of kidney disease from 2008 to 2010. We directly standardized age- and sex-adjusted prevalence rates of proteinuric DKD (proteinuria with or without low estimated glomerular filtration rate [eGFR]) or nonproteinuric DKD (low eGFR alone). We calculated sex-specific odds ratios of DKD in racial/ethnic minorities (relative to NHWs) after adjustment for traditional DKD risk factors.

Racial/ethnic minorities had higher rates of proteinuric DKD than NHWs (24.8–37.9 vs. 24.8%) and lower rates of nonproteinuric DKD (6.3–9.8 vs. 11.7%). On adjusted analyses, Chinese (odds ratio 1.39 for women and 1.56 for men), Filipinos (1.57 for women and 1.85 for men), Hispanics (1.46 for women and 1.34 for men), and NHBs (1.50 for women) exhibited significantly (P < 0.01) higher odds of proteinuric DKD than NHWs. Conversely, Chinese, Hispanic, and NHB women and Hispanic men had significantly lower odds of nonproteinuric DKD than NHWs.

We found novel racial/ethnic differences in DKD among patients with type 2 diabetes. Racial/ethnic minorities were more likely to have proteinuric DKD and less likely to have nonproteinuric DKD. Future research should examine diverse DKD-related outcomes by race/ethnicity to inform targeted prevention and treatment efforts and to explore the etiology of these differences.

This was a prospective study of 3,810 community-living individuals older than 65 years (511 with type 2 diabetes) and free of CVD in 1992 when fetuin-A levels were measured. Participants were followed-up for incident CVD through June 2008.

Mean age was 75 years, and 61% were women; 1,456 participants had an incident CVD event (248 among individuals with type 2 diabetes). The association of fetuin-A with CVD was modified by type 2 diabetes (P interaction = 0.02). Higher fetuin-A was associated with lower CVD risk among persons without type 2 diabetes [hazard ratio per SD 0.1 g/L higher fetuin-A, 0.93 (95% CI, 0.88–0.99)], whereas a trend in the opposite direction was observed among individuals with type 2 diabetes, although it was not statistically significant [1.07 (0.93–1.22)]. Among individuals without type 2 diabetes, similar effect modification was observed by obesity and insulin resistance. Consistently, higher fetuin-A was associated with lower CVD risk only in the subgroups without obesity or with HOMA-IR below the median [0.91 (0.85–0.97) and 0.87 (0.79–0.95), respectively].

The association of fetuin-A with risk of CVD differs among elderly individuals with and without insulin resistance or type 2 diabetes.

We followed 400 nondiabetic Japanese Americans for 10–11 years. Insulin concentrations at 30, 60, and 120 min during a 2-h 75-g OGTT at baseline were used to derive the following possible patterns of insulin: pattern 1 (30-min peak, higher insulin level at 60 than at 120 min), pattern 2 (30-min peak, lower or equal level at 60 vs. 120 min), pattern 3 (60-min peak); pattern 4 (120-min peak, lower level at 30 than at 60 min), and pattern 5 (120-min peak, equal or higher level at 30 vs. 60 min). Insulin sensitivity was estimated by homeostasis model assessment of insulin resistance (HOMA-IR) and Matsuda index. Insulin secretion was estimated by the insulinogenic index (IGI) [insulin/glucose (30–0 min)] and disposition index (IGI/HOMA-IR).

There were 86 incident cases of type 2 diabetes. The cumulative incidence was 3.2, 9.8, 15.4, 47.8, and 37.5% for patterns 1, 2, 3, 4, and 5, respectively. Compared with pattern 1, patterns 4 and 5, characterized by a lasting late insulin response, were associated with significantly less insulin sensitivity as measured by the Matsuda index and lower early insulin response by the disposition index. The multiple-adjusted odds ratios of type 2 diabetes were 12.55 (95% CI 4.79–32.89) for pattern 4 and 8.34 (2.38–29.27) for pattern 5 compared with patterns 1 and 2. This association was independent of insulin secretion and sensitivity.

The patterns of insulin concentration during an OGTT strongly predict the development of type 2 diabetes.

We used electronic medical records from 500 general practices in the U.K. and included data from 285,864 men and women aged 50–84 years from January 2000 to December 2010. We emulated the design and analysis of a hypothetical randomized trial of statins, estimated the observational analog of the intention-to-treat effect, and adjusted for differential survival bias using inverse-probability weighting.

During 1.2 million person-years of follow-up, there were 13,455 cases of type 2 diabetes and 8,932 deaths. Statin initiation was associated with increased risk of type 2 diabetes. The hazard ratio (95% CI) of diabetes was 1.45 (1.39–1.50) before adjusting for potential confounders and 1.14 (1.10–1.19) after adjustment. Adjusting for differential survival did not change the estimates. Initiating atorvastatin and simvastatin was associated with increased risk of type 2 diabetes.

In this sample of the general population, statin therapy was associated with 14% increased risk of type 2 diabetes. Differential survival did not explain this increased risk.

The Coronary Artery Risk Development in Young Adults Study is a multicenter, community-based, longitudinal cohort study of 5,115 white and black adults aged 18–30 years in 1985 to 1986. Years spent abdominally obese were calculated for participants without abdominal obesity (WC >102 cm in men and >88 cm in women) or diabetes at baseline (n = 4,092) and was based upon repeat measurements conducted 2, 5, 7, 10, 15, 20, and 25 years later.

Over 25 years, 392 participants developed incident diabetes. Overall, following adjustment for demographics, family history of diabetes, study center, and time varying WC, energy intake, physical activity, smoking, and alcohol, each additional year of abdominal obesity was associated with a 4% higher risk of developing diabetes [hazard ratio (HR) 1.04 (95% CI 1.02–1.07)]. However, a quadratic model best represented the data. HRs for 0, 1–5, 6–10, 11–15, 16–20, and >20 years of abdominal obesity were 1.00 (referent), 2.06 (1.43–2.98), 3.45 (2.28–5.22), 3.43 (2.28–5.22), 2.80 (1.73–4.54), and 2.91 (1.60–5.29), respectively; P-quadratic < 0.001.

Longer duration of abdominal obesity was associated with substantially higher risk for diabetes independent of the degree of abdominal adiposity. Preventing or at least delaying the onset of abdominal obesity in young adulthood may lower the risk of developing diabetes through middle age.

Japanese type 2 diabetic patients (n = 618) with serum creatinine ≤1.0 mg/dL and without overt proteinuria were enrolled between 1996 and 2000 and followed up until 2011. Baseline urinary L-FABP was measured with an enzyme-linked immunosorbent assay. The primary end points were renal and cardiovascular composites (hemodialysis, myocardial infarction, angina pectoris, stroke, cerebral hemorrhage, and peripheral vascular disease). The secondary renal outcomes were the incidence of a 50% decline in estimated glomerular filtration rate (eGFR), progression to an eGFR <30 mL/min/1.73 m², and the annual decline rate in eGFR.

During a 12-year median follow-up, 103 primary end points occurred. The incidence rate of the primary end point increased in a stepwise manner with increases in urinary L-FABP. In Cox proportional hazards analysis, the adjusted hazard ratio in patients with the highest tertile of urinary L-FBAP was 1.93 (95% CI 1.13–3.29). This relationship was observed even when analyzed separately in normoalbuminuria and microalbuminuria. Patients with the highest tertile of urinary L-FABP also demonstrated a higher incidence of the secondary renal outcomes.

Our results indicate that urinary L-FABP may be a predictive marker for renal and cardiovascular prognosis in type 2 diabetic patients without advanced nephropathy.

A prospective, monocenter, observational study was designed to follow eyes/patients with type 2 diabetes and NPDR (Early Treatment Diabetic Retinopathy Study levels 20 and 35) with no prior laser treatment for 2 years or until development of CSME. A total of 410 patients, one eye per patient, fulfilled the inclusion/exclusion criteria and were included in the study. Ophthalmologic examinations including best corrected visual acuity, fundus photography, and optical coherence tomography were performed at baseline, 6 months, and at the last study visit (24 months or before laser treatment).

A total of 348 eyes/patients performed the 24-month visit or developed CSME. Of these 348 eyes/patients, 26 developed CSME. HbA_1c levels at baseline and MA turnover (i.e., the sum of the MA formation and disappearance rates) computed during the first 6 months of follow-up were found to be independently predictive factors for development of CSME. MA turnover was 11.2 ± 11.2 in the 26 eyes/patients that developed CSME and 5.0 ± 5.2 in the remaining 322 (P < 0.001). Higher MA turnover values correlated with earlier development of CSME. MA turnover predictive values for CSME development were, for the positive predictive value, 20% and for the negative predictive value, 96%.

MA turnover calculated with the RetmarkerDR predicts development of CSME in eyes with NPDR. Low MA turnover values identify well the eyes that are less likely to develop CSME in a 2-year period.

Glycosuria was measured before and after a single ipragliflozin dose in 8 nondiabetic subjects and 57 T2DM patients (age 62 ± 9 years, fasting glucose 133 ± 39 mg/dL, mean ± SD) with normal renal function (assessed as the estimated glomerular filtration rate [eGFR]) (eGFR₁ ≥90 mL · min^–1 · 1.73 m^–2), mild (eGFR₂ ≥60 to <90), moderate (eGFR₃ ≥30 to <60), or severe reduction in eGFR (eGFR₄ ≤15 to <30).

Ipragliflozin significantly increased urinary glucose excretion in each eGFR class (P < 0.0001). However, ipragliflozin-induced glycosuria declined (median [IQR]) across eGFR class (from 46 mg/min [33] in eGFR₁ to 8 mg/min [7] in eGFR₄, P < 0.001). Ipragliflozin-induced fractional glucose excretion (excretion/filtration) was 39% [27] in the T2DM patients (pooled data), similar to that of the nondiabetic subjects (37% [17], P = ns). In bivariate analysis of the pooled data, ipragliflozin-induced glycosuria was directly related to eGFR and fasting glucose (P < 0.0001 for both, r² = 0.55), predicting a decrement in 24-h glycosuria of 15 g for each 20 mL/min decline in eGFR and an increase of 7 g for each 10 mg/dL increase in glucose above fasting normoglycemia.

In T2DM patients, ipragliflozin increases glycosuria in direct, linear proportion to GFR and degree of hyperglycemia, such that its amount can be reliably predicted in the individual patient. Although absolute glycosuria decreases with declining GFR, the efficiency of ipragliflozin action (fractional glucose excretion) is maintained in patients with severe renal impairment.

The relationship between retinopathy, its 4-year progression, and CV outcomes (CV death or nonfatal myocardial infarction or stroke) was analyzed in participants in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial who also participated in the ACCORD Eye Study. Retinopathy was classified as either none, mild, moderate, or severe, and worsening was classified as a <2-step, 2–3-step, or >3-step change (that included incident laser therapy or vitrectomy).

Participants (n = 3,433) of mean age 61 years had baseline retinal photographs (seven stereoscopic fields). Compared with no retinopathy, the adjusted HRs (95% CI) for the CV outcome rose from 1.49 (1.12–1.97) for mild retinopathy to 2.35 (1.47–3.76) for severe retinopathy. A subset of 2,856 was evaluated for progression of diabetic retinopathy at 4 years. The hazard of the primary outcome increased by 38% (1.38 [1.10–1.74]) for every category of change in retinopathy severity. Additional adjustment for the baseline and follow-up levels of A1C, systolic blood pressure, and lipids either individually or together rendered the relationships between worsening and CV outcomes nonsignificant.

Both the severity of retinopathy and its progression are determinants of incident CV outcomes. The retina may provide an anatomical index of the effect of metabolic and hemodynamic factors on future CV outcomes.

Fifty-four patients with type 2 diabetes mellitus underwent comprehensive neurologic assessment, nerve-conduction studies, and nerve-excitability assessment. Neuropathy severity was assessed using the Total Neuropathy Score. Neuropathy-specific QoL was assessed using a DN-specific QoL questionnaire (Neuropathy-Specific Quality of Life Questionnaire [NeuroQoL]). Glycosylated hemoglobin and BMI were recorded in all patients.

NeuroQoL scores indicated significant QoL impairment (mean 9.08 ± 5.93). Strength-duration time constant (SDTC), an excitability parameter reflecting sodium channel function, was strongly correlated with QoL scores (r = 0.545; P < 0.005). SDTC was prolonged in 48.6% of patients who experienced neuropathic symptoms. A significant correlation was also noted between SDTC and neuropathy severity (r = 0.29; P < 0.05). This relationship was strengthened when looking specifically at patients with clinically graded neuropathy (r = 0.366; P < 0.05).

The current study has demonstrated an association between markers of sodium channel function and QoL in DN. The study demonstrates that excitability techniques may identify patients in whom altered sodium channel function may be the dominant abnormality. The findings suggest that excitability techniques may have a role in clinical decision making regarding neuropathic treatment prescription.

In a double-blind, controlled, randomized, crossover study, 19 patients with T2DM received, on two different occasions, beverages containing either AGE-BLG or C-BLG. We measured macrovascular [brachial ultrasound of flow-mediated dilatation (FMD)] and microvascular (laser-Doppler measurements of reactive hyperemia in the hand) functions at baseline (T₀), 90 (T₉₀), and 180 (T₁₈₀) min.

Following the AGE-BLG, FMD decreased at T₉₀ by 80% from baseline and remained decreased by 42% at T₁₈₀ (P < 0.05 vs. baseline, P < 0.05 vs. C-BLG at T90). By comparison, following C-BLG, FMD decreased by 27% at T₉₀ and 51% at T₁₈₀ (P < 0.05 vs. baseline at T180). A significant decrease in nitrite (T₁₈₀) and nitrate (T₉₀ and T₁₈₀), as well as a significant increase in N-carboxymethyllisine, accompanied intake of AGE-BLG. There was no change in microvascular function caused by either beverage.

In patients with T2DM, acute oral administration of a single AGE-modified protein class significantly though transiently impaired macrovascular function in concert with decreased nitric oxide bioavailability. These AGE-related changes were independent of heat treatment.

From January 2000 to December 2002, patients with type 2 diabetes aged 25–75 years without chronic kidney disease (estimated glomerular filtration rate ≥60 mL/min/1.73 m²) were consecutively recruited (n = 1,217) and followed-up in January 2011 and May 2012. Severe hypoglycemia (SH) was defined as an event requiring the assistance of another person to actively administer glucose, hospitalization, or medical care in an emergency department. We used Cox proportional hazard regression analysis to test the association between SH episodes and potential explanatory variables.

After a median 10.4 years of follow-up, 111 (12.6%) patients experienced 140 episodes of SH, and the incidence was 1.55 per 100 patient-years. Mean age and duration of diabetes were 55.3 ± 9.8 and 9.8 ± 6.5 years, respectively. The incidence of SH events was higher in older patients (P < 0.001), in those with a longer duration of diabetes (P < 0.001), in those who used insulin (P < 0.001) and sulfonylurea (P = 0.003), and in those who had macroalbuminuria (P < 0.001) at baseline. Cox hazard regression analysis revealed that SH was associated with longer duration of diabetes and the presence of macroalbuminuria (normoalbuminuria versus macroalbuminuria: hazard ratio, 2.52; 95% CI 1.31–4.84; P = 0.006).

The development of SH was independently associated with duration of diabetes and presence of macroalbuminuria, even with normal renal function in patients with type 2 diabetes.

Renal function, blood pressure, and plasma cyclic guanosine monophosphate (cGMP) were measured in 20 men and 15 women with type 1 diabetes mellitus during clamped euglycemia and clamped hyperglycemia. Renal function, blood pressure, and plasma cGMP responses to graded infusions of intravenous l-arginine and N^G-monomethyl-l-arginine (l-NMMA) were measured during clamped hyperglycemia.

Subjects were young, normotensive, normoalbuminuric men and women who adhered to a high-sodium, moderate-protein diet. Plasma cGMP levels during euglycemia were generally lower in men compared with women, and systolic blood pressure (SBP) was higher in men. In response to hyperglycemia, cGMP levels did not change in men but did decline in women (–1.10 ± 0.20 vs. +0.05 ± 0.20 pmol/L, between-group effect of hyperglycemia on cGMP; P = 0.012). Hyperglycemia also was associated with an increase in SBP, glomerular filtration rate (GFR) (124 ± 6 to 143 ± 7 mL/min/1.73 m²; P = 0.003) and filtration fraction (FF) in women, but these parameters did not change in men. In response to l-arginine during hyperglycemia, the increase in cGMP was exaggerated in women versus men and GFR and FF decreased in women only, back toward baseline values observed during clamped euglycemia. l-NMMA infusion did not exaggerate changes in hemodynamic function in response to hyperglycemia.

 l-Arginine reversed the renal hemodynamic effects of hyperglycemia in women, suggesting that nitric oxide is an important regulator of sex-dependent vascular responses to hyperglycemia in humans.

Subjects were overweight/obese adults with type 2 diabetes mellitus (T2DM) with available fitness data at 4 years (n = 3,942).This clinical trial randomized subjects to DSE or ILI. DSE subjects received standard care plus information related to diet, PA, and social support three times per year. ILI subjects received weekly intervention contact for 6 months, which was reduced over the 4-year period, and were prescribed diet and PA. Measures included weight, fitness, PA, and HbA_1c.

The difference in percent fitness change between ILI and DSE at 4 years was significant after adjustment for baseline fitness and change in weight (3.70 vs. 0.94%; P < 0.01). At 4 years, PA increased by 348 (1,562) kcal/week in ILI vs. 105 (1,309) kcal/week in DSE (P < 0.01). Fitness change at 4 years was inversely related to change in HbA_1c after adjustment for clinical site, treatment, baseline HbA_1c, prescribed diabetes medication, baseline fitness, and weight change (P < 0.01). Change in PA was not related to change in HbA_1c.

A 4-year ILI increased fitness and PA in overweight/obese individuals with T2DM. Change in fitness was associated with improvements in glycemic control, which provides support for interventions to improve fitness in adults with T2DM.

This study is a multicenter, randomized, double-blind, placebo-controlled clinical trial. A total of 304 type 2 diabetic patients with CAD, mean age = 63.3 years (range, 36–80 years), were enrolled. Participants were randomly assigned to receive either glipizide (30 mg daily) or metformin (1.5 g daily) for 3 years. The primary end points were times to the composite of recurrent cardiovascular events, including death from a cardiovascular cause, death from any cause, nonfatal myocardial infarction, nonfatal stroke, or arterial revascularization.

At the end of study drug administration, both groups achieved a significant decrease in the level of glycated hemoglobin (7.1% in the glipizide group and 7.0% in the metformin group). At a median follow-up of 5.0 years, 91 participants had developed 103 primary end points. Intention-to-treat analysis showed an adjusted hazard ratio (HR) of 0.54 (95% CI 0.30–0.90; P = 0.026) for the composites of cardiovascular events among the patients that received metformin, compared with glipizide. The secondary end points and adverse events were not significantly different between the two groups.

Treatment with metformin for 3 years substantially reduced major cardiovascular events in a median follow-up of 5.0 years compared with glipizide. Our results indicated a potential benefit of metformin therapy on cardiovascular outcomes in high-risk patients.

Among 375 consecutive type 2 diabetic patients undergoing quantitative coronary angiography (QCA) and intravascular ultrasound (IVUS), 82 patients with nonsignificant stenosis (luminal diameter narrowing <30% [group I]) and 190 patients with significant CAD (luminal diameter stenosis ≥70% [group II]) were included for analysis of apoA-I glycation level and serum activity of lecithin: cholesterol acyltransferase (LCAT). The control group had 136 healthy subjects. At the 1-year follow-up, angiography and IVUS were repeated mainly in group II patients for plaque progression assessment.

Relative intensity of apoA-I glycation by densitometry was increased, and serum LCAT activity was decreased stepwise across groups control, I, and II. These two measurements were associated with the number of diseased coronary arteries and extent index in group II. During 1-year follow-up, QCA detected 45 patients with plaque progression in 159 subjects, and IVUS found 38 patients with plaque progression in 127 subjects. Baseline relative intensity of apoA-I glycation was significantly increased in patients with plaque progression compared with those without, with values associated with changes in QCA and IVUS measurements. Multivariable regression analysis revealed that baseline relative intensity of apoA-I glycation was an independent determinant of CAD and plaque progression in type 2 diabetic patients.

ApoA-I glycation level is associated with the severity of CAD and coronary artery plaque progression in type 2 diabetic patients.

Within the population-based Cooperative Health Research in the Region of Augsburg (KORA) S4 study, we measured A-SAA concentrations in 836 initially nondiabetic subjects (55–74 years of age) without clinically overt inflammation who participated in a 7-year follow-up examination including an oral glucose tolerance test.

A-SAA concentrations were significantly associated with incident type 2 diabetes (odds ratio [OR] for a one-SD increase of A-SAA adjusted for age and sex = 1.28 [95% CI 1.08–1.53], P = 0.005), particularly in younger subjects (P value for interaction = 0.047). The association attenuated when adjusting for parameters of glucose metabolism (fasting glucose, fasting insulin, HbA_1c, and 2-h glucose; OR 1.16 [0.95–1.42], P = 0.15). Similar analyses for high-sensitive C-reactive protein (hs-CRP) yielded the following ORs: 1.39 (1.10–1.68, P = 0.0006) and 1.13 (0.88–1.45, P = 0.34), respectively. In contrast, A-SAA concentrations were significantly associated with 2-h glucose levels at follow-up even after adjustment for parameters of glucose metabolism (P = 0.008, n = 803).

Our findings indicate similarly strong prospective associations with type 2 diabetes for A-SAA and hs-CRP and suggest a potential causal link via postchallenge hyperglycemia.

A total of 333 asymptomatic type 2 diabetic patients without history of CAD underwent exercise electrocardiogram or myocardial perfusion scintigraphy for detection of silent myocardial ischemia, and those whose test results were positive were subjected to coronary computed tomography angiography or coronary angiography. The ability of carotid IMT to identify severe CAD corresponding to treatment with revascularization was examined by receiver-operating characteristic (ROC) curve analyses.

Among the 333 subjects, 17 were treated with revascularization. A multiple logistic regression analysis showed that maximum IMT was an independent predictor of severe CAD even after adjustment for conventional risk factors. ROC curve analyses revealed that the addition of maximum IMT to conventional risk factors significantly improved the prediction ability for severe CAD (from area under the curve, 0.67 to 0.79; P = 0.039). The greatest sensitivity and specificity were obtained when the cut-off value of maximum IMT was set at 2.45 mm (pretest probability, 5%; posttest probability, 11%; sensitivity, 71%). When we applied age-specific cut-off values, the sensitivity of screening further increased in both the nonelderly (pretest probability, 6%; posttest probability, 10%; sensitivity, 100%) and the elderly subjects (pretest probability, 5%; posttest probability, 15%; sensitivity, 100%).

Our study suggests that carotid maximum IMT is useful for screening asymptomatic type 2 diabetic patients with severe CAD equivalent to revascularization.

The SOS study involved 2,010 obese patients who underwent bariatric surgery (68% vertical-banded gastroplasty, 19% banding, and 13% gastric bypass) and 2,037 contemporaneously matched obese controls receiving usual care. At inclusion, the participant age was 37–60 years and BMI was ≥34 kg/m² in men and ≥38 kg/m² in women. The effect of surgery was assessed in patients that do (n = 3,814) and do not (n = 233) meet current eligibility criteria. The date of analysis was 1 January 2012. The follow-up time was up to 20 years, with a median of 10 years.

Cardiovascular risk factors were significantly improved both in noneligible and eligible individuals after 10 years of follow-up. Surgery reduced the diabetes incidence in both the noneligible (adjusted hazard ratio 0.33 [95% CI 0.13–0.82], P = 0.017) and eligible (0.27 [0.22–0.33], P < 0.001) groups. We could not detect a difference in the effect of surgery between the groups (adjusted interaction P value = 0.713).

Bariatric surgery drastically reduced the incidence of type 2 diabetes both in noneligible and eligible patients and improved cardiovascular risk factors in both groups. Our results show that strict BMI cutoffs are of limited use for bariatric surgery prioritization if the aim is to prevent diabetes and improve cardiovascular risk factors.

The incremental exercise testing with cycle ergometer was performed in 14 male patients with MetS and 13 age-, sex-, and activity-matched healthy subjects. Systemic lipid peroxidation was assessed by serum thiobarbituric acid reactive substances (TBARS), and systemic antioxidant defense capacity was assessed by serum total thiols and enzymatic activity of superoxide dismutase (SOD). To assess skeletal muscle energy metabolism, we measured high-energy phosphates in the calf muscle during plantar flexion exercise and intramyocellular lipid (IMCL) in the resting leg muscle, using ³¹P- and ¹proton-magnetic resonance spectroscopy, respectively.

Serum TBARS were elevated (12.4 ± 7.1 vs. 3.7 ± 1.1 μmol/L; P < 0.01), and serum total thiols and SOD activity were decreased (290.8 ± 51.2 vs. 398.7 ± 105.2 μmol/L, P < 0.01; and 22.2 ± 8.4 vs. 31.5 ± 8.5 units/L, P < 0.05, respectively) in patients with MetS compared with healthy subjects. Peak VO₂ and anaerobic threshold normalized to body weight were significantly lower in MetS patients by 25 and 31%, respectively, and inversely correlated with serum TBARS (r = –0.49 and r = –0.50, respectively). Moreover, muscle phosphocreatine loss during exercise was 1.4-fold greater in patients with MetS (P < 0.05), and IMCL content was 2.9-fold higher in patients with MetS (P < 0.01), indicating impaired skeletal muscle energy metabolism, and these indices positively correlated with serum TBARS (r = 0.45 and r = 0.63, respectively).

Systemic oxidative stress was associated with lower aerobic capacity and impaired skeletal muscle energy metabolism in patients with MetS.

In 1998, 1,143 primary care patients with type 2 diabetes participated in the ZODIAC study. Because blood was drawn for 867 patients (76%) and confounders were missing for 19 patients, the final study sample comprised 848 patients. After a follow-up time of 10 years, we used Cox proportional hazard models to evaluate the relationship between MR-proANP and (cardiovascular) mortality. Harrell C statistic was used to compare models with and without MR-proANP. The regression analyses were repeated without MR-proANP for patients aged older than 75 years.

Median MR-proANP in the total study sample was 75 pmol/L (interquartile range, 48–124 pmol/L). During follow-up, 354 (42%) out of 848 patients had died, of whom 152 (43%) deaths were attributable to cardiovascular factors. MR-proANP was independently associated with all-cause and cardiovascular mortality, irrespective of age. During old age, there was a significant inverse relationship between blood pressure and mortality. This relationship did not change after adjustment for MR-proANP.

MR-proANP is independently associated with mortality in patients with type 2 diabetes. MR-proANP did not influence the inverse relationship between blood pressure and mortality in elderly patients.

Two-hundred twenty-nine obese youths (87 Caucasians, 61 African Americans, and 81 Hispanics; mean age, 12.8 ± 2.9 years; mean BMI, 31.4 ± 7.4) underwent magnetic resonance imaging, oral glucose tolerance test, and CK-18 levels measurement; 12 subjects underwent liver biopsy.

African Americans showed lower CK-18 levels than Hispanics (P < 0.001) and Caucasians (P = 0.004). Hepatic fat content (HFF%) and whole body insulin sensitivity index (WBISI) modulated CK-18 levels in Caucasians and Hispanics (P = 0.02 and P = 0.011), but not in African Americans; in fact, CK-18 was associated with HFF% and WBISI in Caucasians (P = 0.0018 and P < 0.0001) and Hispanics (P < 0.0001 and P = 0.02), but not in African Americans (both P = 0.5). The PNPLA3 SNP showed association in Caucasians (P = 0.02) and Hispanics (P = 0.05), and FDFT1 SNP showed an association in Caucasians (P = 0.05) and Hispanics (P = 0.02), with the same trend in African Americans (P = 0.07).

African Americans have lower levels of CK-18 than Caucasians and Hispanics irrespective of HFF% and insulin resistance. Moreover, SNPs in the PNPLA3 and FDFT1 may drive the individual predisposition to development of hepatic injury.

In a historical prospective cohort study of subjects from the Clalit Health Services database, which includes information on nearly 4 million people, diabetes-free subjects aged 40–70 years with serum 25-hydroxycholecalciferol (25-OHD) measurements available were followed for 2 years to assess the development of IFG and diabetes in five 25-OHD subgroups: ≥25, 25.1–37.5, 37.6–50, 50.1–75, and >75 nmol/L.

The baseline cohort included 117,960 adults: 83,526 normoglycemic subjects and 34,434 subjects with IFG. During follow-up, 8,629 subjects (10.3% of the normoglycemic group) developed IFG, and 2,162 subjects (1.8% of the total cohort) progressed to diabetes. A multivariable model adjusted for age, sex, population group, immigrant status, BMI, season of vitamin D measurement, LDL and HDL cholesterol, triglycerides, estimated glomerular filtration rate, history of hypertension or cardiovascular disease, Charlson comorbidity index, smoking, and socioeconomic status revealed an inverse association between 25-OHD and the risk of progression to IFG and diabetes. The odds of transitioning from normoglycemia to IFG, from normoglycemia to diabetes, and from IFG to diabetes in subjects with a 25-OHD level ≤25 nmol/L were greater than those of subjects with a 25-OHD level >75 nmol/L [odds ratio 1.13 (95% CI 1.03–1.24), 1.77 (1.11–2.83), and 1.43 (1.16–1.76), respectively].

Vitamin D deficiency appears to be an independent risk factor for the development of IFG and diabetes.

Patients were randomized to EQW (2 mg) or detemir (once or twice daily, titrated to achieve fasting plasma glucose ≤5.5 mmol/L) for 26 weeks. The primary outcome was proportion of patients achieving A1C ≤7.0% and weight loss ≥1.0 kg at end point, analyzed by means of logistic regression. Secondary outcomes included measures of glycemic control, cardiovascular risk factors, and safety and tolerability.

Of 216 patients (intent-to-treat population), 111 received EQW and 105 received detemir. Overall, 44.1% (95% CI, 34.7–53.9) of EQW-treated patients compared with 11.4% (6.0–19.1) of detemir-treated patients achieved the primary outcome (P < 0.0001). Treatment with EQW resulted in significantly greater reductions than detemir in A1C (least-square mean ± SE, –1.30 ± 0.08% vs. –0.88 ± 0.08%; P < 0.0001) and weight (–2.7 ± 0.3 kg vs. +0.8 ± 0.4 kg; P < 0.0001). Gastrointestinal-related and injection site–related adverse events occurred more frequently with EQW than with detemir. There was no major hypoglycemia in either group. Five (6%) patients in the EQW group and six (7%) patients in the detemir group experienced minor hypoglycemia; only one event occurred without concomitant sulfonylureas (detemir group).

Treatment with EQW resulted in a significantly greater proportion of patients achieving target A1C and weight loss than treatment with detemir, with a low risk of hypoglycemia. These results suggest that EQW is a viable alternative to insulin detemir treatment in patients with type 2 diabetes with inadequate glycemic control using oral antidiabetes drugs.

Seventy-one normal-weight (BMI <25 kg/m²) Hispanic women (age, 20–39 years) participated in a fasting blood draw for glucose, insulin, lipids, and inflammatory markers; a glucose tolerance test; anthropometric and blood pressure measurements; body composition by dual-energy x-ray absorptiometry; and measurements of cardiorespiratory fitness via Vo_2max and daily physical activity by accelerometer.

Six percent of participants had impaired fasting glucose, 14% had impaired glucose tolerance, and 48% had at least one cardiovascular disease risk factor. Homeostasis model assessment of insulin resistance (HOMA-IR) and fasting insulin were positively correlated with glucose, triglycerides, systolic blood pressure, and diastolic blood pressure, and were negatively correlated with adiponectin (P < 0.05). The 2-h insulin was positively correlated with diastolic blood pressure, triglycerides, and high-sensitivity C-reactive protein. HOMA-IR and fasting insulin remained significantly and positively related to glucose, triglycerides, and blood pressure after adjustment for body composition. The relationships between markers of insulin resistance and adiponectin and high-sensitivity C-reactive protein were attenuated after adjustment for body composition.

Surrogate markers of insulin resistance were associated with cardiovascular disease risk factors and inflammation in young, normal-weight, Hispanic women. Our findings suggest that HOMA-IR, fasting, and 2-h insulin may be important clinical markers for identifying young, normal-weight, Hispanic women who may be at risk for development of type 2 diabetes and cardiovascular disease. Our findings show the importance of early screening for prevention of type 2 diabetes and cardiovascular disease in this population.

Five members of the American Diabetes Association and five members of The Endocrine Society with expertise in different aspects of hypoglycemia were invited by the Chair, who is a member of both, to participate in a planning conference call and a 2-day meeting that was also attended by staff from both organizations. Subsequent communications took place via e-mail and phone calls. The writing group consisted of those invitees who participated in the writing of the manuscript. The workgroup meeting was supported by educational grants to the American Diabetes Association from Lilly USA, LLC and Novo Nordisk and sponsorship to the American Diabetes Association from Sanofi. The sponsors had no input into the development of or content of the report.

The writing group considered data from recent clinical trials and other studies to update the prior workgroup report. Unpublished data were not used. Expert opinion was used to develop some conclusions.

Consensus was achieved by group discussion during conference calls and face-to-face meetings, as well as by iterative revisions of the written document. The document was reviewed and approved by the American Diabetes Association’s Professional Practice Committee in October 2012 and approved by the Executive Committee of the Board of Directors in November 2012 and was reviewed and approved by The Endocrine Society’s Clinical Affairs Core Committee in October 2012 and by Council in November 2012.

The workgroup reconfirmed the previous definitions of hypoglycemia in diabetes, reviewed the implications of hypoglycemia on both short- and long-term outcomes, considered the implications of hypoglycemia on treatment outcomes, presented strategies to prevent hypoglycemia, and identified knowledge gaps that should be addressed by future research. In addition, tools for patients to report hypoglycemia at each visit and for clinicians to document counseling are provided.

A systematic search of the MEDLINE and Embase databases and a hand search of references from original reports were conducted up to 31 October 2012. Prospective observational studies that assessed the association between blood levels of 25(OH)D and risk of incident type 2 diabetes were included for meta-analysis. DerSimonian and Laird’s random-effects model was used. A quadratic spline regression analysis was used to examine the shape of the association with a generalized least-squares trend test performed for the dose-response relation.

A total of 21 prospective studies involving 76,220 participants and 4,996 incident type 2 diabetes cases were included for meta-analysis. Comparing the highest to the lowest category of 25(OH)D levels, the summary relative risk for type 2 diabetes was 0.62 (95% CI 0.54–0.70). A spline regression model showed that higher 25(OH)D levels were monotonically associated with a lower diabetes risk. This inverse association did not differ by sex, duration of follow-up, study sample size, diabetes diagnostic criteria, or 25(OH)D assay method. A linear trend analysis showed that each 10 nmol/L increment in 25(OH)D levels was associated with a 4% lower risk of type 2 diabetes (95% CI 3–6; P for linear trend < 0.0001).

Our meta-analysis showed an inverse and significant association between circulating 25(OH)D levels and risk of type 2 diabetes across a broad range of blood 25(OH)D levels in diverse populations.