We randomly assigned 51 type 1 diabetic patients to ALA (600 mg once daily) or placebo for 5 weeks. Platelet reactivity was evaluated by the PFA-100 method and by measuring CD41 and CD62 platelet expression. C-reactive protein (CRP) and 8-iso-prostaglandin F2α serum levels also were measured.

Baseline variables were similar in the two groups. After treatment, closure time was longer (P = 0.006) and CD62P platelet expression was lower, both before (P = 0.002) and after (P = 0.009) ADP stimulation in the ALA group compared with the placebo group. CRP and 8-iso-prostaglandin F2α levels showed no differences between the two groups.

Our data show that ALA reduces measures of platelet reactivity ex vivo in type 1 diabetic patients, independently of antioxidant or anti-inflammatory effects.

Patients (n = 105: 58 diffuse and 47 focal congenital hyperinsulinism) received operations between 1984 and 2006. Follow-up consisted of periodic measurements of pre- and postprandial plasma glucose over 24 h, OGTT, and IVGTT. Cumulative incidence of hypo- or hyperglycemia/insulin treatment was estimated by Kaplan-Meier analysis.

After near-total pancreatectomy, 59% of children with diffuse congenital hyperinsulinism still presented mild or asymptomatic hypoglycemia that responded to medical treatments and disappeared within 5 years. One-third of the patients had both preprandial hypoglycemia and postprandial hyperglycemia. Hyperglycemia was found in 53% of the patients immediately after surgery; its incidence increased regularly to 100% at 13 years. The cumulative incidence of insulin-treated patients was 42% at 8 years and reached 91% at 14 years, but the progression to insulin dependence was very variable among the patients. Plasma insulin responses to IVGTT and OGTT correlated well with glycemic alterations. In focal congenital hyperinsulinism, hypoglycemia or hyperglycemia were rare, mild, and transient.

Patients with focal congenital hyperinsulinism are cured of hypoglycemia after limited surgery, while the outcome of diffuse congenital hyperinsulinism is very variable after near-total pancreatectomy. The incidence of insulin-dependent diabetes is very high in early adolescence.

After a run-in phase, 146 children with type 1 diabetes (mean age 7.5 ± 1.7 years, 64% on pumps, median diabetes duration 3.5 years) were randomly assigned to CGM or to usual care. The primary outcome was reduction in HbA_1c at 26 weeks by ≥0.5% without the occurrence of severe hypoglycemia.

The primary outcome was achieved by 19% in the CGM group and 28% in the control group (P = 0.17). Mean change in HbA_1c was –0.1% in each group (P = 0.79). Severe hypoglycemia rates were similarly low in both groups. CGM wear decreased over time, with only 41% averaging at least 6 days/week at 26 weeks. There was no correlation between CGM use and change in HbA_1c (r_s = –0.09, P = 0.44). CGM wear was well tolerated, and parental satisfaction with CGM was high. However, parental fear of hypoglycemia was not reduced.

CGM in 4- to 9-year-olds did not improve glycemic control despite a high degree of parental satisfaction with CGM. We postulate that this finding may be related in part to limited use of the CGM glucose data in day-to-day management and to an unremitting fear of hypoglycemia. Overcoming the barriers that prevent integration of these critical glucose data into day-to-day management remains a challenge.

A total of 443 participants with IGT originally randomized to a lifestyle intervention or control group were studied. IS and AIGR_0–30 were estimated from an oral tolerance glucose test administered annually during the 4-year follow-up trial and were related to the risk of diabetes onset over a 6-year follow-up.

Lifestyle intervention resulted in higher IS (P = 0.02) and lower unadjusted AIGR_0–30 (P = 0.08) during the 4-year follow-up. A higher IS and a lower BMI during the follow-up were associated with a lower unadjusted AIGR_0–30 during the follow-up, independently of study group (P < 0.001). A greater increase in IS on the median cutoff point of a 0.69 increase was associated with higher IS-adjusted AIGR_0–30 during the follow-up (P = 0.002). In multivariate models, IS and IS-adjusted AIGR_0–30 were both inversely associated with diabetes incidence (P < 0.001). Participants who progressed to type 2 diabetes were more obese and had lower IS and Matsuda IS index-AIGR_0–30 than nonprogressors.

Our results indicate that the reduction in the risk of developing type 2 diabetes after lifestyle intervention is related to the improvement of IS along with weight loss. Improved IS may also have beneficial effects on preservation of β-cell function.

Type 2 diabetic patients (aged 50–75 years) with eGFR ≥30 mL/min/1.73 m² were randomly allocated to a fixed dose of fenofibrate (200 mg daily) (n = 4,895) or placebo (n = 4,900) for 5 years. Baseline renal function (Modification of Diet in Renal Disease equation) was grouped by eGFR (30–59, 60–89, and ≥90 mL/min/1.73 m²). The prespecified outcome was total cardiovascular events (composite of cardiovascular death, myocardial infarction, stroke, and coronary/carotid revascularization). Serious adverse events and instances of ESRD (plasma creatinine >400 μmol/L, dialysis, renal transplant, or renal death) were recorded. Analysis was by intention to treat.

Overall, fenofibrate reduced total cardiovascular events, compared with placebo (hazard ratio 0.89 [95% CI 0.80–0.99]; P = 0.035). This benefit was not statistically different across eGFR groupings (P = 0.2 for interaction) (eGFR 30–59 mL/min/1.73 m²: 0.68 [0.47–0.97], P = 0.035; eGFR ≥90 mL/min/1.73 m²: 0.85 [0.70–1.02], P = 0.08). ESRD rates were similar between treatment arms, without adverse safety signals of fenofibrate use in renal impairment.

Patients with type 2 diabetes and moderate renal impairment benefit from long-term fenofibrate, without excess drug-related safety concerns compared with those with no or mild renal impairment. Fenofibrate treatment should not be contraindicated in moderate renal impairment, suggesting that current guidelines may be too restrictive.

Despite being medicated, patients with type 2 diabetes have elevated CVD risk, particularly postmenopausal women. Although dietary flavonoids have been shown to reduce CVD risk factors in healthy participants, no long-term trials have examined the additional benefits of flavonoids to CVD risk in medicated postmenopausal women with type 2 diabetes. We conducted a parallel-design, placebo-controlled trial with type 2 diabetic patients randomized to consume 27 g/day (split dose) flavonoid-enriched chocolate (containing 850 mg flavan-3-ols [90 mg epicatechin] and 100 mg isoflavones [aglycone equivalents)]/day) or matched placebo for 1 year.

Ninety-three patients completed the trial, and adherence was high (flavonoid 91.3%; placebo 91.6%). Compared with the placebo group, the combined flavonoid intervention resulted in a significant reduction in estimated peripheral insulin resistance (homeostasis model assessment of insulin resistance [HOMA-IR] –0.3 ± 0.2; P = 0.004) and improvement in insulin sensitivity (quantitative insulin sensitivity index [QUICKI] 0.003 ± 0.00; P = 0.04) as a result of a significant decrease in insulin levels (–0.8 ± 0.5 mU/L; P = 0.02). Significant reductions in total cholesterol:HDL-cholesterol (HDL-C) ratio (–0.2 ± 0.1; P = 0.01) and LDL-cholesterol (LDL-C) (–0.1 ± 0.1 mmol/L; P = 0.04) were also observed. Estimated 10-year total coronary heart disease risk (derived from UK Prospective Diabetes Study algorithm) was attenuated after flavonoid intervention (flavonoid +0.1 ± 0.3 vs. placebo 1.1 ± 0.3; P = 0.02). No effect on blood pressure, HbA_1c, or glucose was observed.

One-year intervention with flavan-3-ols and isoflavones improved biomarkers of CVD risk, highlighting the additional benefit of flavonoids to standard drug therapy in managing CVD risk in postmenopausal type 2 diabetic patients.

We used multivariable regression models to examine the association between food insecurity and poor glycemic control using a cross-sectional survey and chart review of 711 patients with diabetes in safety net health clinics. We then examined whether difficulty following a diabetic diet, self-efficacy, or emotional distress related to diabetes mediated the relationship between food insecurity and glycemic control.

The food insecurity prevalence in our sample was 46%. Food-insecure participants were significantly more likely than food-secure participants to have poor glycemic control, as defined by hemoglobin A_1c ≥8.5% (42 vs. 33%; adjusted odds ratio 1.48 [95% CI 1.07–2.04]). Food-insecure participants were more likely to report difficulty affording a diabetic diet (64 vs. 49%, P < 0.001). They also reported lower diabetes-specific self-efficacy (P < 0.001) and higher emotional distress related to diabetes (P < 0.001). Difficulty following a healthy diet and emotional distress partially mediated the association between food insecurity and glycemic control.

Food insecurity is an independent risk factor for poor glycemic control in the safety net setting. This risk may be partially attributable to increased difficulty following a diabetes-appropriate diet and increased emotional distress regarding capacity for successful diabetes self-management. Screening patients with diabetes for food insecurity may be appropriate, particularly in the safety net setting.

Baseline and intervention data were obtained from 10,149 participants in a Finnish National Diabetes Prevention Project.

In total, 36% of men and 52% of women perceived the need for counseling. Most of the risk factors did not increase the perceived need for counseling. Those agreeing to attend supervised lifestyle intervention were more likely to report a perceived need than those who agreed on a self-initiated lifestyle change or those who refused to attend lifestyle intervention. The perceived need was associated with actual attendance in the lifestyle intervention only among women.

It will be vital to find additional means to support lifestyle change.

Three open questions were administered to 120 patients (43 with T1DM and 77 with T2DM) who had been randomized at least 2 years before to be followed by group care and 121 (41 T1DM and 80 T2DM) who had always been on usual care. The responses were analyzed by propositional analysis, by identifying the focal nuclei, i.e., the terms around which all sentences are organized, and then other predicates, according to their hierarchical relationship to the nuclear proposition. Specific communicative units were arbitrarily classified into three categories: attitudes, empowerment, and locus of control.

Patients on group care showed more positive attitudes, higher sense of empowerment, and more internal locus of control than those on usual care. In addition, they expressed a wider and more articulated range of concepts associated with the care received and made less use of medical terminology (P < 0.001, all). Higher HbA_1c was associated with negative attitudes (P = 0.025) and negative empowerment (P = 0.055).

Group treatment reinforces communication and peer identification and may achieve its clinical results by promoting awareness, self-efficacy, positive attitudes toward diabetes and the setting of care, an internal locus of control, and, ultimately, empowerment in the patients.

Seven adult subjects from three NDM families and one family with type 2 diabetes were studied. Insulin secretion and insulin sensitivity were assessed using clamp techniques. We screened 139 type 2 diabetic patients who were well controlled by SU for ABCC8 mutations.

ABCC8 mutation carriers exhibited glucose intolerance, frank diabetes, or insulin-requiring diabetes since diagnosis. HbA_1c improved in five SU-treated patients. Insulin secretion capacity was impaired in three patients compared with adult control subjects but was restored after a 4-week SU trial in two patients. Cohort screening revealed four SU-treated patients with ABCC8 mutations, two of which are likely causal.

Although of rare occurrence, recognition of adult-onset ABCC8-associated diabetes may help in targeting patients for SU therapy.

Patients were randomized to subcutaneous (SC) EQW 2.0 mg + oral placebo (n = 248), MET 2,000 mg/day + SC placebo (n = 246), PIO 45 mg/day + SC placebo (n = 163), or SITA 100 mg/day + SC placebo (n = 163) for 26 weeks. MET and PIO therapies were increased to maximum-tolerated dosages. Injections with EQW or placebo were administered weekly, while oral medication or placebo was administered daily.

Baseline characteristics were as follows: 59% men, 67% Caucasian, mean age 54 years, HbA_1c 8.5%, fasting serum glucose 9.9 mmol/L, body weight 87.0 kg, and diabetes duration 2.7 years. HbA_1c reductions (%) at 26 weeks (least-squares means) with EQW versus MET, PIO, and SITA were –1.53 vs. –1.48 (P = 0.620), –1.63 (P = 0.328), and –1.15 (P < 0.001), respectively. Weight changes (kg) were –2.0 vs. –2.0 (P = 0.892), +1.5 (P < 0.001), and –0.8 (P < 0.001), respectively. Common adverse events were as follows: EQW, nausea (11.3%) and diarrhea (10.9%); MET, diarrhea (12.6%) and headache (12.2%); PIO, nasopharyngitis (8.6%) and headache (8.0%); and SIT, nasopharyngitis (9.8%) and headache (9.2%). Minor (confirmed) hypoglycemia was rarely reported. No major hypoglycemia occurred.

EQW was noninferior to MET but not PIO and superior to SITA with regard to HbA_1c reduction at 26 weeks. Of the agents studied, EQW and MET provided similar improvements in glycemic control along with the benefit of weight reduction and no increased risk of hypoglycemia.

Recruited were 506 study 1 and 392 study 2 adults with type 2 diabetes from community medical groups. Multiple regression equations associated the DDS17, a 17-item scale that yields a mean-item score, with HbA_1c, diabetes self-efficacy, diet, and physical activity. Associations also were undertaken for the two-item DDS (DDS2) screener. Analyses included control variables, linear, and quadratic (curvilinear) DDS terms.

Significant quadratic effects occurred between the DDS17 and each diabetes variable, with increases in distress associated with poorer outcomes: study 1 HbA_1c (P < 0.02), self-efficacy (P < 0.001), diet (P < 0.001), physical activity (P < 0.04); study 2 HbA_1c (P < 0.03), self-efficacy (P < 0.004), diet (P < 0.04), physical activity (P = NS). Substantive curvilinear associations with all four variables in both studies began at unexpectedly low levels of DDS17: the slope increased linearly between scores 1 and 2, was more muted between 2 and 3, and reached a maximum between 3 and 4. This suggested three patient subgroups: little or no distress, <2.0; moderate distress, 2.0–2.9; high distress, ≥3.0. Parallel findings occurred for the DDS2.

In two samples of type 2 diabetic patients we found a consistent pattern of curvilinear relationships between the DDS and HbA_1c, diabetes self-efficacy, diet, and physical activity. The shape of these relationships suggests cut points for three patient groups: little or no, moderate, and high distress.

We identified all patients aged >16 years with cardiovascular events in England between 2004–2005 and 2009–2010 using national hospital activity data. Diabetes- and nondiabetes-specific rates were calculated for each year. To test for time trend, we fitted Poisson regression models.

In people with diabetes, admission rates for angina, AMI, and CABG decreased significantly by 5% (rate ratio 0.95 [95% CI 0.94–0.96]), 5% (0.95 [0.93–0.97]), and 3% (0.97 [0.95–0.98]) per year, respectively. Admission rates for stroke did not significantly change (0.99 [0.98–1.004]) but increased for PCI (1.01 [1.005–1.03]) in people with diabetes. People with and without diabetes experienced similar proportional changes for all outcomes, with no significant differences in trends between these groups. However, diabetes was associated with an ~3.5- to 5-fold risk of CVD events. In-hospital mortality rates declined for AMI and stroke, remained unchanged for CABG, and increased for PCI admissions in both groups.

This national study suggests similar changes in admissions for CVD in people with and without diabetes. Aggressive risk reduction is needed to further reduce the high absolute and relative risk of CVD still present in people with diabetes.

We calculated NLEA hospitalization rates, by diabetes status, among persons aged ≥40 years on the basis of National Hospital Discharge Survey data on NLEA procedures and National Health Interview Survey data on diabetes prevalence. We used joinpoint regression to calculate the annual percentage change (APC) and to assess trends in rates from 1988 to 2008.

The age-adjusted NLEA discharge rate per 1,000 persons among those diagnosed with diabetes and aged ≥40 years decreased from 11.2 in 1996 to 3.9 in 2008 (APC –8.6%; P < 0.01), while rates among persons without diagnosed diabetes changed little. NLEA rates in the diabetic population decreased significantly from 1996 to 2008 in all demographic groups examined (all P < 0.05). Throughout the entire study period, rates of diabetes-related NLEA were higher among persons aged ≥75 years than among those who were younger, higher among men than women, and higher among blacks than whites.

From 1996 to 2008, NLEA discharge rates declined significantly in the U.S. diabetic population. Nevertheless, NLEA continues to be substantially higher in the diabetic population than in the nondiabetic population and disproportionately affects people aged ≥75 years, blacks, and men. Continued efforts are needed to decrease the prevalence of NLEA risk factors and to improve foot care among certain subgroups within the U.S. diabetic population that are at higher risk.

A total of 1,000,000 individuals were randomly sampled from the National Health Insurance database, and incident cases of bladder cancer during the period from 1 January 2006 to 31 December 2009 were analyzed among 54,928 patients with type 2 diabetes and without previous bladder cancer.

Among 165 incident case subjects, 10 (0.39%) were ever users and 155 (0.30%) were never users of pioglitazone (adjusted hazard ratio in full model 1.305 [95% CI 0.661–2.576]). All bladder cancer in ever users occurred within a duration of therapy <24 months, suggesting an early effect of pioglitazone on bladder cancer or late use of pioglitazone in high-risk patients.

The association between pioglitazone and bladder cancer was not significant. However, confirmation of this finding is required because of the possible lack of statistical power owing to the small number of events.

This was a cross-sectional study with 269 subjects with type 2 diabetes who were divided into four groups based on estimated glomerular filtration rate (eGFR) using Modification of Diet in Renal Disease (eGFR_MDRD) formula: 57 in control, 111 in CKD stages 1–2, 78 in stage 3, and 23 in stages 4–5.

The study groups differed significantly with respect to 1,5-AG and fasting plasma glucose (FPG), age, duration of diabetes, blood pressure, HDL, and percentage of antihypertension or antidyslipidemia medication use. Stepwise multivariate regression analyses showed that 1,5-AG levels in the control group, the CKD stages 1–2 group, and the CKD stage 3 group could be explained by HbA_1c, age, duration of diabetes, FPG, and antihypertension medication. However, eGFR_MDRD was the only independent determinant of 1,5-AG levels in CKD stages 4–5. Logarithmic transformed 1,5-AG values (ln[1,5-AG]) had significant inverse correlations with HbA_1c and FPG levels for CKD stages 1–2 and CKD stage 3 (all P < 0.001). However, associations between ln(1,5-AG) and HbA_1c or FPG were insignificant for CKD stages 4–5 (P = 0.274 and P = 0.080, respectively).

This study demonstrated that 1,5-AG levels do not appear to be influenced by mild or moderate renal dysfunction, suggesting it is a reliable glycemic marker in type 2 diabetes with CKD stages 1–3.

Seventeen index T2D risk variants were genotyped in 2,652 African American case subjects with T2D and 1,393 nondiabetic control subjects. Individual SNPs and cumulative risk allele loads were assessed for association with risk for T2D. Cumulative risk was assessed by counting risk alleles and evaluating the difference in cumulative risk scores between case subjects and control subjects. A second analysis weighted risk scores (ln [OR]) based on previously reported European-derived effect sizes.

Frequencies of risk alleles ranged from 8.6 to 99.9%. Eleven SNPs had ORs >1, and 5 from ADAMTS9, WFS1, CDKAL1, JAZF1, and TCF7L2 trended or had nominally significant evidence of T2D association (P < 0.05). Individuals carried between 13 and 29 risk alleles. Association was observed between T2D and increase in risk allele load (unweighted OR 1.04 [95% CI 1.01–1.08], P = 0.010; weighted 1.06 [1.03–1.10], P = 8.10 x 10^–5). When TCF7L2 SNP rs7903146 was included as a covariate, the risk score was no longer associated with T2D in either model (unweighted 1.02 [0.98–1.05], P = 0.33; weighted 1.02 [0.98–1.06], P = 0.40).

The trend of increase in risk for T2D with increasing risk allele load is similar to observations in European-derived populations; however, these analyses indicate that T2D genetic risk is primarily mediated through the effect of TCF7L2 in African Americans.

We analyzed data for 4,657 subjects (1,404 fathers, 1,404 mothers, 957 sons, and 892 daughters) from the Korean National Health and Nutrition Examination Surveys conducted between 1998 and 2008.

Compared with adolescents whose parents did not have MetS, the odds ratio (95% CI) for MetS in adolescents with MetS in one parent was 4.2 (2.1–8.5) and 8.7 (3.4–22.3) in those with MetS in both parents. Among obese adolescents, the prevalence of MetS was 18.2% without parental MetS, whereas 29.2% of obese adolescents with MetS in one parent and 53.9% with MetS in both parents also had MetS (P = 0.01 for trend).

The risk of MetS increased significantly in adolescents with parental MetS and was especially high in those with coexisting obesity and parental MetS.

A total of 733 Japanese Americans were followed for 16.9 years. Hazard ratios (HRs) per interquartile range increase in VF were calculated using time-dependent Cox proportional hazard models censored at age 82 years, with age as the time axis adjusted for sex and smoking.

Higher VF was associated with all-cause mortality (HR 1.39 [95% CI 1.11–1.75] 107 deaths) and obesity-related mortality (1.39 [1.04–1.85], 68 deaths from cardiovascular disease, diabetes, or obesity-related cancer). After further adjustment for waist circumference, VF remained significantly associated with all-cause mortality (1.41 [1.04–1.92]) but not with obesity-related mortality. The associations between mortality and VF were not independent of BMI.

VF was associated with all-cause mortality and obesity-related mortality in Japanese Americans. VF did not significantly improve mortality risk assessment beyond that of BMI.

Data were obtained from >350 U.K. primary care practices in a retrospective cohort study. All individuals with or without diabetes who developed a first tumor after January 1990 were identified and records were followed to December 2009. Diabetes was further stratified by treatment regimen. Cox proportional hazards models were used to compare all-cause mortality from all cancers and from specific cancers.

Of 112,408 eligible individuals, 8,392 (7.5%) had type 2 diabetes. Cancer mortality was increased in those with diabetes, compared with those without (hazard ratio 1.09 [95% CI 1.06–1.13]). Mortality was increased in those with breast (1.32 [1.17–1.49]) and prostate cancer (1.19 [1.08–1.31]) but decreased in lung cancer (0.84 [0.77–0.92]). When analyzed by diabetes therapy, mortality was increased relative to nondiabetes in those on monotherapy with sulfonylureas (1.13 [1.05–1.21]) or insulin (1.13 [1.01–1.27]) but reduced in those on metformin monotherapy (0.85 [0.78–0.93]).

This study confirmed that type 2 diabetes was associated with poorer prognosis after incident cancer, but that the association varied according to diabetes therapy and cancer site. Metformin was associated with survival benefit both in comparison with other treatments for diabetes and in comparison with a nondiabetic population.

The analysis samples include adults aged ≥20 years from the National Health and Nutrition Examination Survey (NHANES) 1988–1994 and the NHANES 1999–2008 who self-reported having diabetes (n = 1,065, NHANES 1988–1994; n = 1,872, NHANES 1999–2008). By use of logistic regression models, we examined the correlates of binary indicators measuring 1) high blood glucose, 2) high blood pressure, 3) high cholesterol, and 4) smoking.

Control of blood glucose, blood pressure, and cholesterol improved among individuals with diabetes between the NHANES 1988–1994 and the NHANES 1999–2008, but there was no change in smoking prevalence. In the NHANES 1999–2008, racial/ethnic minorities and individuals without some college education were more likely to have poorly controlled blood glucose compared with non-Latino whites and those with some college education. In addition, individuals with diabetes who had at least some college education were less likely to smoke and had better blood pressure control compared with individuals with diabetes without at least some college education.

Trends in CVD risk factors among individuals with diabetes improved over the past 2 decades, but racial/ethnic- and education-related disparities have emerged in some areas.

The researchers conducted a prospective, occupational-based study of local government employees in Sapporo, Japan. Between April 2003 and March 2004, 3,570 nondiabetic participants, aged 35–55 years, underwent annual health checkups and completed a self-administered questionnaire that included information on sleep duration/quality and FHD at baseline. Having diabetes was defined as taking medication for diabetes or a fasting plasma glucose level of ≥126 mg/dL at follow-up (2007–2008).

A total of 121 (3.4%) new cases of diabetes were reported. In multivariate logistic regression models of workers without an FHD, and after adjustment for potential confounding factors, the odds ratio (95% CI) for developing diabetes was 5.37 (1.38–20.91) in those with a sleep duration of ≤5 h compared with those with a sleep duration of >7 h. Other risk factors were awakening during the night (5.03 [1.43–17.64]), self-perceived insufficient sleep duration (6.76 [2.09–21.87]), and unsatisfactory overall quality of sleep (3.71 [1.37–10.07]). In subjects with an FHD, these associations were either absent or weaker.

The current study shows that poor sleep is associated with a higher risk of developing diabetes in workers without an FHD. Promoting healthy sleeping habits may be effective for preventing the development of diabetes in people without an FHD.

Using 2002–2003 World Health Survey data (n = 121,051 individuals; 35 low- and middle-income countries), we examined possession of medications to treat diabetes and estimated the relationship between out-of-pocket medical spending (2005 international dollars), catastrophic medical spending, and diabetes. We assessed whether health insurance modified these relationships.

Diabetic individuals experience differentially higher out-of-pocket medical spending, particularly among individuals with high levels of spending (excess spending of $157 per year [95% CI 130–184] at the 95th percentile), and a greater chance of incurring catastrophic medical spending (17.8 vs. 13.9%; difference 3.9% [95% CI 0.2–7.7]) compared with otherwise similar individuals without diabetes. Diabetic individuals with insurance do not have significantly lower risks of catastrophic medical spending (18.6 vs. 17.7%; difference not significant), nor were they significantly more likely to possess diabetes medications (22.8 vs. 20.6%; difference not significant) than those who were otherwise similar but without insurance. These effects were more pronounced and significant in lower-income countries.

In low-income countries, despite insurance, diabetic individuals are more likely to experience catastrophic medical spending and often do not possess appropriate medications to treat diabetes. Research into why policies in these countries may not adequately protect people from catastrophic spending or enhance possession of critical medications is urgently needed.

Analysis of data on U.S. adults ≥50 years of age with (n = 1,621) or without type 2 diabetes (n = 6,867) from the National Health and Nutrition Examination Survey (NHANES), 1999–2006. Type 2 diabetes was defined as clinical diagnosis after age 30 without initiation of insulin therapy within 1 year. Those with diabetes were classified according to their current metformin use. Biochemical B₁₂ deficiency was defined as serum B₁₂ concentrations ≤148 pmol/L and borderline deficiency was defined as >148 to ≤221 pmol/L.

Biochemical B₁₂ deficiency was present in 5.8% of those with diabetes using metformin compared with 2.4% of those not using metformin (P = 0.0026) and 3.3% of those without diabetes (P = 0.0002). Among those with diabetes, metformin use was associated with biochemical B₁₂ deficiency (adjusted odds ratio 2.92; 95% CI 1.26–6.78). Consumption of any supplement containing B₁₂ was not associated with a reduction in the prevalence of biochemical B₁₂ deficiency among those with diabetes, whereas consumption of any supplement containing B₁₂ was associated with a two-thirds reduction among those without diabetes.

Metformin therapy is associated with a higher prevalence of biochemical B₁₂ deficiency. The amount of B₁₂ recommended by the Institute of Medicine (IOM) (2.4 μg/day) and the amount available in general multivitamins (6 μg) may not be enough to correct this deficiency among those with diabetes.

This retrospective cohort study of 30,897 patients with diabetes aimed to determine whether lifestyle counseling is associated with time to A1C, blood pressure, and LDL cholesterol control in patients with diabetes. Patients were included if they had at least 2 years of follow-up with primary care practices affiliated with two teaching hospitals in eastern Massachusetts between 1 January 2000 and 1 January 2010.

Comparing patients with face-to-face counseling rates of once or more per month versus less than once per 6 months, median time to A1C <7.0% was 3.5 versus 22.7 months, time to blood pressure <130/85 mmHg was 3.7 weeks versus 5.6 months, and time to LDL cholesterol <100 mg/dL was 3.5 versus 24.7 months, respectively (P < 0.0001 for all). In multivariable analysis, one additional monthly face-to-face lifestyle counseling episode was associated with hazard ratios of 1.7 for A1C control (P < 0.0001), 1.3 for blood pressure control (P < 0.0001), and 1.4 for LDL cholesterol control (P = 0.0013).

Lifestyle counseling in the primary care setting is strongly associated with faster achievement of A1C, blood pressure, and LDL cholesterol control. These results confirm that the findings of controlled clinical trials are applicable to the routine care setting and provide evidence to support current treatment guidelines.

We analyzed the dynamics of fasting serum levels of 12 traditional metabolic biomarkers and novel adipokines among 322 participants in the 2-year Dietary Intervention Randomized Controlled Trial (DIRECT) of low-fat, Mediterranean, or low-carbohydrate diets for weight loss.

We identified two distinct patterns: Pattern A includes biomarkers (insulin, triglycerides, leptin, chemerin, monocyte chemoattractant protein 1, and retinol-binding protein 4) whose dynamics tightly correspond to changes in body weight, with the trend during the weight loss phase (months 0–6) going in the opposite direction to that in the weight maintenance/regain phase (months 7–24) (P < 0.05 between phases, all biomarkers). Pattern B includes biomarkers (high molecular weight adiponectin, HDL cholesterol [HDL-C], high-sensitivity C-reactive protein [hsCRP], fetuin-A, progranulin, and vaspin) that displayed a continued, cumulative improvement (P < 0.05 compared with baseline, all biomarkers) throughout the intervention. These patterns were consistent across sex, diabetic groups, and diet groups, although the magnitude of change varied. Hierarchical analysis suggested similar clusters, revealing that the dynamic of leptin (pattern A) was most closely linked to weight change and that the dynamic of hsCRP best typified pattern B.

hsCRP, HDL-C, adiponectin, fetuin-A, progranulin, and vaspin levels display a continued long-term improvement despite partial weight regain. This may likely reflect either a delayed effect of the initial weight loss or a continuous beneficial response to switching to healthier dietary patterns.

A randomized, parallel-group trial tested 16 glucose-tolerant nonobese relatives (8 subjects in the endurance training group and 8 subjects in the resistance training group) before and after 26 weeks of endurance or resistance training. Exercise performance was assessed from power output and oxygen uptake (Vo₂) during incremental tests and from maximal torque of knee flexors (MaxT_flex) and extensors (MaxT_ext) using isokinetic dynamometry. fATP and ectopic lipids were measured with ¹H/³¹P magnetic resonance spectroscopy.

Endurance training increased power output and Vo₂ by 44 and 30%, respectively (both P < 0.001), whereas resistance training increased MaxT_ext and MaxT_flex by 23 and 40%, respectively (both P < 0.001). Across all groups, insulin sensitivity (382 ± 90 vs. 389 ± 40 mL ⋅ min^–1 ⋅ m^–2) and ectopic lipid contents were comparable after exercise training. However, 8 of 16 relatives had 26% greater fATP, increasing from 9.5 ± 2.3 to 11.9 ± 2.4 μmol ⋅ mL^–1 ⋅ m^–1 (P < 0.05). Six of eight responders were carriers of the G/G single nucleotide polymorphism rs540467 of the NDUFB6 gene (P = 0.019), which encodes a subunit of mitochondrial complex I.

Moderate exercise training for 6 months does not necessarily improve insulin sensitivity but may increase ATP synthase flux. Genetic predisposition can modify the individual response of the ATP synthase flux independently of insulin sensitivity.

We studied 18 healthy male subjects (mean age 25.6 ± 3.0 years; mean BMI 26.6 ± 4.8 kg/m²). Serum and plasma BDNF concentration was measured in the baseline state and in the 120 and 360 min of euglycemic hyperinsulinemic clamp with or without intralipid/heparin infusion. Furthermore, plasma BDNF was measured in 20 male subjects (mean age 22.7 ± 2.3 years; mean BMI 24.9 ± 1.5 kg/m²) 360 min after a high-fat meal.

Insulin sensitivity was reduced by ~40% after 6 h of intralipid/heparin infusion (P < 0.001). During both clamps, serum and plasma BDNF followed the same pattern. Hyperinsulinemia had no effect on circulating BDNF. Raising FFA had no effect on circulating BDNF in 120 min; however, it resulted in a significant decrease by 43% in serum and by 35% in plasma BDNF after 360 min (P = 0.005 and 0.006, respectively). High-fat meal also resulted in a decrease by 27.8% in plasma BDNF (P = 0.04).

Our data show that raising FFA decreases circulating BDNF. This might indicate a potential link between FFA-induced insulin resistance and neurodegenerative disorders.

Sixteen obesity-predisposing single nucleotide polymorphisms (SNPs) were tested for association with short-term (baseline to 6 months) and long-term (baseline to 2 years) weight loss and weight regain (6 months to study end).

Irrespective of treatment, the Ala12 allele at PPARG associated with short- and long-term weight loss (–0.63 and –0.93 kg/allele, P ≤ 0.005, respectively). Gene–treatment interactions were observed for short-term (LYPLAL1 rs2605100, P_{lifestyle*SNP} = 0.032; GNPDA2 rs10938397, P_{lifestyle*SNP} = 0.016; MTCH2 rs10838738, P_{lifestyle*SNP} = 0.022) and long-term (NEGR1 rs2815752, P_{metformin*SNP} = 0.028; FTO rs9939609, P_{lifestyle*SNP} = 0.044) weight loss. Three of 16 SNPs were associated with weight regain (NEGR1 rs2815752, BDNF rs6265, PPARG rs1801282), irrespective of treatment. TMEM18 rs6548238 and KTCD15 rs29941 showed treatment-specific effects (P_{lifestyle*SNP} < 0.05).

Genetic information may help identify people who require additional support to maintain reduced weight after clinical intervention.

The aim of our study was to evaluate with magnetic resonance imaging and nuclear magnetic resonance spectroscopy (¹H MRS) the cerebral morphology and metabolism of 15 ESRD plus T1D patients, 23 patients with ESRD plus T1D after KD (n = 9) and KP (n = 14) transplantation, and 8 age-matched control subjects.

Magnetic resonance imaging showed a higher prevalence of cerebrovascular disease in ESRD plus T1D patients (53% [95% CI 36–69]) compared with healthy subjects (25% [3–6], P = 0.04). Brain ¹H MRS showed lower levels of N-acetyl aspartate (NAA)-to-choline ratio in ESRD plus T1D, KD, and KP patients compared with control subjects (control subjects vs. all, P < 0.05) and of NAA-to-creatine ratio in ESRD plus T1D compared with KP and control subjects (ESRD plus T1D vs. control and KP subjects, P ≤ 0.01). The evaluation of the most common scores of psychological and neuropsychological function showed a generally better intellectual profile in control and KP subjects compared with ESRD plus T1D and KD patients.

Diabetes and ESRD are associated with a precocious form of brain impairment, chronic cerebrovascular disease, and cognitive decline. In KP-transplanted patients, most of these features appeared to be near normalized after a 5-year follow-up period of sustained normoglycemia.

Subjects (n = 54) were given a high-fat meal (75 g fat, 5 g carbohydrate, 6 g protein) after an overnight fast (nonobese control [NOC]: age 39.9 ± 11.8 years [mean ± SD], BMI 24.9 ± 3.2 kg/m², n = 9; obese: age 43.8 ± 9.5 years, BMI 33.3 ± 2.5 kg/m², n = 15; impaired glucose tolerance [IGT]: age 41.7 ± 11.3 years, BMI 32.0 ± 4.5 kg/m², n = 12; type 2 diabetic: age 45.4 ± 10.1 years, BMI 30.3 ± 4.5 kg/m², n = 18). Blood was collected before (0 h) and after the meal (1–4 h) for analysis.

Baseline endotoxin was significantly higher in the type 2 diabetic and IGT subjects than in NOC subjects, with baseline circulating endotoxin levels 60.6% higher in type 2 diabetic subjects than in NOC subjects (P < 0.05). Ingestion of a high-fat meal led to a significant rise in endotoxin levels in type 2 diabetic, IGT, and obese subjects over the 4-h time period (P < 0.05). These findings also showed that, at 4 h after a meal, type 2 diabetic subjects had higher circulating endotoxin levels (125.4%) than NOC subjects (P < 0.05).

These studies have highlighted that exposure to a high-fat meal elevates circulating endotoxin irrespective of metabolic state, as early as 1 h after a meal. However, this increase is substantial in IGT and type 2 diabetic subjects, suggesting that metabolic endotoxinemia is exacerbated after high fat intake. In conclusion, our data suggest that, in a compromised metabolic state such as type 2 diabetes, a continual snacking routine will cumulatively promote their condition more rapidly than in other individuals because of the greater exposure to endotoxin.

We conducted a comparison study of the developed equation with many other anthropometric indices regarding its correlation with actual BF% in a large cohort of 6,510 white subjects from both sexes (67% female) representing a wide range of ages (18–80 years) and adiposity. Additionally, a validation study in a separate cohort (n = 1,149) and a further analysis of the clinical usefulness of this prediction equation regarding its association with cardiometabolic risk factors (n = 634) was carried out.

The mean BF% in the cohort of 6,510 subjects determined by air displacement plethysmography was 39.9 ± 10.1%, and the mean BF% estimated by the CUN-BAE was 39.3 ± 8.9% (SE of the estimate, 4.66%). In this group, BF% calculated with the CUN-BAE showed the highest correlation with actual BF% (r = 0.89, P < 0.000001) compared with other anthropometric measures or BF% estimators. Similar agreement was found in the validation sample. Moreover, BF% estimated by the CUN-BAE exhibits, in general, better correlations with cardiometabolic risk factors than BMI as well as waist circumference in the subset of 634 subjects.

CUN-BAE is an easy-to-apply predictive equation that may be used as a first screening tool in clinical practice. Furthermore, our equation may be a good tool for identifying patients at cardiovascular and type 2 diabetes risk.

We studied 50 consecutive type 2 diabetic individuals without a history of ischemic heart disease, hepatic diseases, or excessive alcohol consumption, in whom NAFLD was diagnosed by ultrasonography. A tissue Doppler echocardiography with myocardial strain measurement was performed in all patients.

Thirty-two patients (64%) had NAFLD, and when compared with the other 18 patients, age, sex, BMI, waist circumference, hypertension, smoking, diabetes duration, microvascular complication status, and medication use were not significantly different. In addition, the left ventricular (LV) mass and volumes, ejection fraction, systemic vascular resistance, arterial elasticity, and compliance were also not different. NAFLD patients had lower e' (8.2 ± 1.5 vs. 9.9 ± 1.9 cm/s, P < 0.005) tissue velocity, higher E-to-e' ratio (7.90 ± 1.3 vs. 5.59 ± 1.1, P < 0.0001), a higher time constant of isovolumic relaxation (43.1 ± 10.1 vs. 33.2 ± 12.9 ms, P < 0.01), higher LV–end diastolic pressure (EDP) (16.5 ± 1.1 vs. 15.1 ± 1.0 mmHg, P < 0.0001), and higher LV EDP/end diastolic volume (0.20 ± 0.03 vs. 0.18 ± 0.02 mmHg, P < 0.05) than those without steatosis. Among the measurements of LV global longitudinal strain and strain rate, those with NAFLD also had higher E/global longitudinal diastolic strain rate during the early phase of diastole (E/SR_E). All of these differences remained significant after adjustment for hypertension and other cardiometabolic risk factors.

Our data show that in patients with type 2 diabetes and NAFLD, even if the LV morphology and systolic function are preserved, early features of LV diastolic dysfunction may be detected.

Participants were drawn from representative samples of adults living in England and Scotland. Cox proportional hazards regression models were used to relate baseline plasma CRP with all-cause and CVD mortality during follow-up in men and women with and without diabetes. The added value of CRP to the predictions was assessed through c-statistic comparison and relative integrated discrimination improvement.

A total of 25,979 participants (4.9% with diabetes) were followed for a median of 93 months, during which period there were 2,767 deaths (957 from CVD). CRP (per SD log_e) was associated with a 53% (95% CI 43–64) and 43% (38–49) higher risk of cardiovascular and all-cause mortality, respectively. These associations were log linear and did not differ according to diabetes status (both P ≥ 0.08 for interaction), sex, and other risk factors. Adding CRP to conventional risk factors improved predictions overall and separately by diabetes status but not for CVD mortality, although such improvements only were marginal based on several discrimination statistics.

The association between CRP and CVD was similar across diabetes status, and the effects are broadly similar across levels of other conventional risk factors.

Forty-eight patients (24 subjects with good [HbA_1c <7.4%] and 24 subjects with poor [HbA_1c >8.4%] glycemic control) were randomly assigned to treatment with 75 or 320 mg/day aspirin during 4 weeks in a crossover fashion. A 4-week washout period separated the treatment periods. The plasma fibrin network was assessed by determination of the permeability coefficient (K_s).

Treatment with 75 mg aspirin did not influence fibrin network permeability (K_s). However, K_s increased significantly during treatment with 320 mg aspirin (P = 0.004), and a significant treatment effect was seen compared with treatment with 75 mg aspirin (P = 0.009). The increase in K_s during high-dose aspirin treatment was significant in patients with poor glycemic control (P = 0.02), whereas K_s only tended to increase in patients with good glycemic control (P = 0.06).

A high dose of aspirin is required to influence fibrin network permeability in patients with type 1 diabetes. The observed lack of effect with low-dose aspirin may contribute to aspirin treatment failure in diabetes.

A total of 10,096 ACCORD study participants with follow-up for both hypoglycemia and mortality were included. Hazard ratios (95% CIs) relating the risk of death to the updated annualized number of hypoglycemic episodes and the updated annualized number of intervals with unrecognized hypoglycemia were obtained using Cox proportional hazards regression models, allowing for these hypoglycemia variables as time-dependent covariates and controlling for the baseline covariates.

Participants in the intensive group reported a mean of 1.06 hypoglycemic episodes (self-monitored blood glucose <70 mg/dL or <3.9 mmol/L) in the 7 days preceding their regular 4-month visit, whereas participants in the standard group reported an average of 0.29 episodes. Unrecognized hypoglycemia was reported, on average, at 5.8% of the intensive group 4-month visits and 2.6% of the standard group visits. Hazard ratios for mortality in models including frequency of hypoglycemic episodes were 0.93 (95% CI 0.9–0.97; P < 0.001) for participants in the intensive group and 0.98 (0.91–1.06; P = 0.615) for participants in the standard group. The hazard ratios for mortality in models, including unrecognized hypoglycemia, were not statistically significant for either group.

Recognized and unrecognized hypoglycemia was more common in the intensive group than in the standard group. In the intensive group of the ACCORD study, a small but statistically significant inverse relationship of uncertain clinical importance was identified between the number of hypoglycemic episodes and the risk of death among participants.

Total and HMW adiponectin were measured in a population-based study of older adults. The relations of total adiponectin, HMW adiponectin, and their ratio with incident diabetes (n = 309) were assessed in 3,802 individuals.

Total and HMW adiponectin were highly correlated (r = 0.94). Analysis using cubic splines revealed that the associations between total and HMW adiponectin and new-onset diabetes were not linear. Specifically, after adjustment for confounders, there were similar inverse relationships for total (hazard ratio per SD 0.49 [95% CI 0.39–0.63]) and HMW adiponectin (0.42 [0.32–0.56]) with diabetes up to values of 20 and 10 mg/L, respectively, above which the associations plateaued. These associations persisted after adjustment for potential mediators (blood pressure, lipids, C-reactive protein, and homeostasis model assessment of insulin resistance [HOMA-IR]). There was, however, evidence of interaction by HOMA-IR in the lower range of adiponectin, with stronger inverse associations among insulin-sensitive than insulin-resistant participants. HMW-to-total adiponectin ratio showed a linear adjusted association with outcome, but this was abolished by inclusion of mediating variables.

In this older cohort, increasing concentrations of total and HMW adiponectin were associated with comparably lower risks of diabetes, but these associations leveled off with further increases above concentrations of 20 and 10 mg/L, respectively. The more pronounced risk decreases at the lower range among participants without insulin resistance support a role for adiponectin that is independent of baseline hyperinsulinemia, but this will require further investigation.

In 793 individuals of the Dutch Famine Birth Cohort, we analyzed the interaction between three SIRT1 single nucleotide polymorphisms (SNPs) and prenatal exposure to famine on type 2 diabetes risk.

In the total population (exposed and unexposed), SIRT1 variants were not associated with type 2 diabetes. A significant interaction was found between two SIRT1 SNPs and exposure to famine in utero on type 2 diabetes risk (P = 0.03 for rs7895833; P = 0.01 for rs1467568). Minor alleles of these SNPs were associated with a lower prevalence of type 2 diabetes only in individuals who had been exposed to famine prenatally (odds ratio for rs7895833 0.50 [95% CI 0.24–1.03], P = 0.06; for rs1467568 0.48 [0.25–0.91], P = 0.02).

SIRT1 may be an important genetic factor involved in fetal programming during malnutrition, influencing type 2 diabetes risk later in life.

We analyzed the expression of proinflammatory cytokines and adhesion molecules in the inferior epigastric artery walls of type 1 diabetic patients with CKD (n = 22) and compared it with nondiabetic uremic patients (n = 92) at the time of kidney transplantation. We evaluated the expression of interleukin (IL)-6, monocyte chemotractant protein (MCP)-1, vascular cell adhesion molecule (VCAM)-1, intercellular adhesion molecule-1, and the activation of nuclear factor-β p65 (NFkB-p65). Common carotid intima-media thickness (c-IMT) was determined by conventional echography.

IL-6, MCP-1, and VCAM-1 proteins were elevated in type 1 diabetic patients compared with nondiabetic subjects (P < 0.05). The nuclear localization of NFkB-p65 was higher in type 1 diabetic patients (P < 0.01) and correlated with the levels of MCP-1 in this group (r = 0.726, P < 0.001). Arterial fibrosis correlated with IL-6 and MCP-1 levels (r = 0.411, P < 0.001 and r = 0.378, P = 0.001). A significant correlation was observed between VCAM-1 levels and both the degree of arterial narrowing and c-IMT.

Type 1 diabetes produces a proinflammatory state in the arteries of end-stage CKD patients, with increased levels of IL-6, MCP-1, and VCAM-1, as well as a greater degree of p65 activation, which are associated with more severe vascular lesions and higher c-IMT. Although causality is not demonstrated, these findings support the major role of inflammation in type 1 diabetic patients with CKD.

MEDLINE, EMBASE, and the Cochrane Library were searched from 1950 to June 2010 for trials of at least 12 weeks’ duration in which diabetic patients were treated with either metformin monotherapy or as an add-on therapy. Data on change in HbA_1c were pooled in a meta-analysis. Data from dose-comparison trials were separately pooled.

A total of 35 trials were identified for the main analysis and 7 for the dose-comparison analysis. Metformin monotherapy lowered HbA_1c by 1.12% (95% CI 0.92–1.32; I² = 80%) versus placebo, metformin added to oral therapy lowered HbA_1c by 0.95% (0.77–1.13; I² = 77%) versus placebo added to oral therapy, and metformin added to insulin therapy lowered HbA_1c by 0.60% (0.30–0.91; I² = 79.8%) versus insulin only. There was a significantly greater reduction in HbA_1c using higher doses of metformin compared with lower doses of metformin with no significant increase in side effects.

Evidence supports the effectiveness of metformin therapy in a clinically important lowering of HbA_1c used as monotherapy and in combination with other therapeutic agents. There is potential for using higher doses of metformin to maximize glycemic control in diabetic patients without increasing gastrointestinal effects.