Association of variants in CDKN2A/2B and CDKAL1 genes with gestational insulin sensitivity and disposition in pregnant Han Chinese women

Aims/Introduction

Variants in cell cycle regulation genes, CDKAL1 and CDKN2A/2B, have been suggested to be associated with type 2 diabetes, and also play a role in insulin procession in non-diabetic European individuals. Rs7754580 in CDKAL1 and rs7020996 in CDKN2A/2B were found to be associated with gestational diabetes in Chinese individuals. In order to understand the metabolism mechanism of greatly upregulated maternal insulin signaling during pregnancy and the pathogenesis of gestational diabetes, we investigated the impact of rs7754580 and rs7020996 on gestational insulin regulation and procession.

Materials and Methods

We recruited 1,146 unrelated, non-diabetic, pregnant Han Chinese women (age 28.5 ± 4.1 years, body mass index 21.4 ± 2.6 kg/m²), and gave them oral glucose tolerance tests. The indices of insulin sensitivity, insulin disposition, insulin release and proinsulin to insulin conversion were calculated. Rs7754580 in the CDKAL1 gene and rs7020996 in the CDKN2A/2B gene were genotyped. Under an additive model, we analyzed the associations between the variants and gestational insulin indices using logistic regression.

Results

By adjusting for maternal age, body mass index and the related interactions, CDKAL1 rs7754580 risk allele C was detected to be associated with increased insulin sensitivity (P = 0.011), decreased insulin disposition (P = 0.0002) and 2-h proinsulin conversion (P = 0.017). CDKN2A/2B rs7020996 risk allele T was found to be related to decreased insulin sensitivity (P = 0.002) and increased insulin disposition (P = 0.0001).

Conclusions

The study showed that cell cycle regulating genes might have a distinctive effect on gestational insulin sensitivity, β-cell function and proinsulin conversion in pregnant Han Chinese women.     

Combined use of basal insulin analog and acarbose reduces postprandial glucose in patients with uncontrolled type 2 diabetes

Aims/Introduction

Early initiation of basal insulin therapy is recommended for normalizing fasting blood glucose in type 2 diabetes mellitus. However, basal insulin treatment might not adequately control postprandial glucose levels. The present study evaluated whether the combination of the α-glucosidase inhibitor, acarbose, and basal insulin improved blood glucose control under daily-life treatment conditions in a large sample of Korean patients.

Materials and Methods

The present study was a multicenter, prospective, observational study under daily-life treatment conditions. A total of 539 patients with type 2 diabetes who were treated with basal insulin and additional acarbose were enrolled and followed up for 20 weeks. Changes in hemoglobin A1c, fasting and postprandial blood glucose were evaluated at baseline and at the end of the observation period. The physician and patient satisfaction of the combination treatment and safety were assessed.

Results

Hemoglobin A1c decreased by 0.55 ± 1.05% from baseline (P < 0.0001). Fasting and postprandial blood glucose levels were reduced by 0.89 ± 3.79 and 2.59 ± 4.77 mmol/L (both P < 0.0001). The most frequently reported adverse drug reactions were flatulence (0.37%) and abnormal gastrointestinal sounds (0.37%), and all were mild in intensity and transient. In the satisfaction evaluation, 79.0% of physicians and 77.3% of patients were ‘very satisfied’ or ‘satisfied’ with the combined basal insulin and acarbose therapy.

Conclusions

Combination therapy of basal insulin and acarbose in patients with type 2 diabetes improved glucose control, and had no drug-specific safety concerns, suggesting that the treatment might benefit individuals who cannot control blood glucose with basal insulin alone.     

Liver steatosis is associated with insulin resistance in skeletal muscle rather than in the liver in Japanese patients with non‐alcoholic fatty liver disease

Aims/Introduction

To examine the association between liver histological features and organ-specific insulin resistance indices calculated from 75-g oral glucose tolerance test data in patients with non-alcoholic fatty liver disease.

Materials and Methods

Liver biopsy specimens were obtained from 72 patients with non-alcoholic fatty liver disease, and were scored for steatosis, grade and stage. Hepatic and skeletal muscle insulin resistance indices (hepatic insulin resistance index and Matsuda index, respectively) were calculated from 75-g oral glucose tolerance test data, and metabolic clearance rate was measured using the euglycemic hyperinsulinemic clamp method.

Results

The degree of hepatic steatosis, and grade and stage of non-alcoholic steatohepatitis were significantly correlated with Matsuda index (steatosis r = −0.45, P < 0.001; grade r = −0.54, P < 0.001; stage r = −0.37, P < 0.01), but not with hepatic insulin resistance index. Multiple regression analyses adjusted for age, sex, body mass index and each histological score showed that the degree of hepatic steatosis (coefficient = −0.22, P < 0.05) and grade (coefficient = −0.40, P < 0.01) were associated with Matsuda index, whereas the association between stage and Matsuda index (coefficient = −0.07, P = 0.593) was no longer significant. A similar trend was observed for the association between steatosis and metabolic clearance rate (coefficient = −0.62, P = 0.059).

Conclusions

Liver steatosis is associated with insulin resistance in skeletal muscle rather than in the liver in patients with non-alcoholic fatty liver disease, suggesting a central role of fatty liver in the development of peripheral insulin resistance and the existence of a network between the liver and skeletal muscle.     

Decreased serum CA19‐9 is associated with improvement of insulin resistance and metabolic control in patients with obesity and type 2 diabetes after Roux‐en‐Y gastric bypass

Aims/Introduction

Patients with type 2 diabetes are known to show elevated serum levels of carbohydrate antigen 19-9 (CA19-9). The aim of the present study was to investigate the possible relationships of CA19-9 with metabolic control, insulin resistance (IR), and pancreatic β-cell function in patients with obesity and type 2 diabetes who underwent Roux-En-Y gastric bypass (RYGB).

Materials and Methods

The present study included 81 healthy volunteers, and 33 patients diagnosed with obesity and type 2 diabetes who underwent RYGB. Anthropometry, serum levels of CA19-9, glucose and lipid metabolic profiles, and serum insulin levels were determined at baseline and at 12 weeks after RYGB.

Results

Changes in CA19-9 were significantly and positively correlated with changes in fasting plasma glucose (r = 0.552, P = 0.001), 2-h post-challenge plasma glucose levels (r = 0.623, P = 0.000), glycated hemoglobin levels (r = 0.819, P = 0.000), glycated albumin levels (r = 0.711, P = 0.000), total cholesterol (r = 0.449, P = 0.009) and the Homeostasis Model of Assessment-IR index (r = 0.407, P = 0.019). Furthermore, a multiple stepwise regression analysis showed that the changes in serum levels of CA19-9 were independently and significantly associated with changes in glycated hemoglobin (β = 0.598, P = 0.000), fasting plasma glucose (β = 0.309, P = 0.000) and Homeostasis Model of Assessment-IR (β = 0.235, P = 0.010) after adjusting for confounding factors.

Conclusions

CA19-9 could be an effective indicator of IR, and glycemic and lipid metabolism in patients with obesity and type 2 diabetes after rapid metabolic control by RYGB. Additionally, CA19-9 might be a marker with which to evaluate the short-term effects of glycolipid toxicity on IR in these patients.     

Efficacy and safety of lixisenatide in Japanese patients with type 2 diabetes mellitus inadequately controlled by sulfonylurea with or without metformin: Subanalysis of GetGoal‐S

Aims/Introduction

This was a subanalysis of Japanese patients included in the glucagon-like peptide-1 receptor agonist AVE0010 in patients with type 2 diabetes mellitus for glycemic control and safety evaluation (GetGoal-S) study – a 24-week, randomized, placebo-controlled study of lixisenatide in patients with type 2 diabetes mellitus inadequately controlled by sulfonylurea with or without metformin.

Materials and Methods

In GetGoal-S, 127 Japanese patients received the once-daily prandial glucagon-like peptide-1 receptor agonist lixisenatide 20 μg/day or a matching placebo. The primary outcome was change in glycated hemoglobin.

Results

At week 24, lixisenatide significantly reduced mean glycated hemoglobin (least squares mean difference vs the placebo −1.1% [12 mmol/mol, P < 0.0001]), and significantly more lixisenatide patients reached glycated hemoglobin targets of <7% (53 mmol/mol) and ≤6.5% (48 mmol/mol) vs the placebo. Lixisenatide produced statistically significant reductions in 2-h postprandial plasma glucose (least squares mean difference vs the placebo −8.51 mmol/L, P < 0.0001) and glucose excursion vs the placebo, and significantly reduced fasting plasma glucose (least squares mean difference vs the placebo −0.65 mmol/L, P = 0.0454). Bodyweight decreased with both lixisenatide and the placebo (least squares mean change −1.12 kg for lixisenatide, −1.02 kg for placebo). The overall incidence of adverse events was similar for lixisenatide and the placebo (84.2 and 82.4%, respectively), the most frequent being gastrointestinal disorders (52.6% for lixisenatide vs 29.4% for placebo). The incidence of symptomatic hypoglycemia was higher with lixisenatide vs the placebo (17.1 and 9.8%, respectively), with no cases of severe symptomatic hypoglycemia in either group.

Conclusions

In the Japanese subpopulation of the GetGoal-S study, lixisenatide produced a significant and clinically relevant improvement in glycated hemoglobin, with a pronounced improvement in postprandial plasma glucose, and a good safety and tolerability profile.     

Increasing risk of diabetes mellitus according to liver function alterations in electronic workers

Aims/Introduction

We sought to determine the association between change in fasting plasma glucose (FPG) and levels of liver enzymes, such as aspartate transaminase, alanine transaminase and gamma-glutamyltransferase, from health examinations.

Materials and Methods

A total of 9,393 health screen examinees with no evidence of viral hepatitis, liver diseases, abnormal liver function and diabetes in their past disease history were enrolled in the present study. All the participants underwent three health examinations. Group 1 and 4 were stationary groups of those with normal liver enzyme levels in the first and second health examinations (G1), and abnormal liver enzyme levels in the first and second health check-up (G4). Groups 2 and 3 were altered groups of those with abnormal liver enzyme levels in the first health examination, which became normal in the second health examination (G2), and from a normal liver enzymes level to an abnormal liver enzymes level (G3).

Results

FPG levels were elevated in male participants (P < 0.01), and were related to old age (P < 0.01), drinking (P < 0.01), smoking (P < 0.01) and so on. There was a strong relationship between FPG levels in the last health examination and altered liver function enzyme levels from the first health examination to the second check-up. In other words, group 4 had the highest level of FPG compared with the other groups (G1 < G2 < G3).

Conclusions

An association was observed between FPG levels and abnormal liver function in manufacturing workers. Abnormal liver function can be closely associated with the development of diabetes.     

Chronic obstructive pulmonary disease in women

BACKGROUND:

Little is known about the comparative impact of chronic obstructive pulmonary disease (COPD) between women and men and about women’s response to pulmonary rehabilitation.

OBJECTIVES:

To compare lung function, disability, mortality and response to pulmonary rehabilitation between women and men with COPD.

METHODS:

In the present retrospective study, 68 women (mean age 62.5±8.9 years) and 168 men (mean age 66.3±8.4 years) were evaluated by means of pulmonary function testing and an incremental symptom-limited cycle exercise test. Forty women and 84 men also participated in a 12-week pulmonary rehabilitation program. A 6 min walking test and the chronic respiratory questionnaire were used to assess the effects of pulmonary rehabilitation. Survival status was also evaluated.

RESULTS:

Compared with men, women had a smaller tobacco exposure (31±24 versus 48±27 pack-years, P<0.05), displayed better forced expiratory volume in 1 s (44±13 versus 39±14 % predicted, P<0.05), a higher functional residual capacity (161±37 versus 149±36 % predicted, P<0.05) and total lung capacity (125±20 versus 115±19 % predicted, P<0.001). Peak oxygen consumption was not different between women and men when expressed in predicted values but lower in women when expressed in absolute values. Pulmonary rehabilitation resulted in significant improvements in 6 min walking test and quality of life in both sexes, but women had a greater improvement in chronic respiratory questionnaire dyspnea. Survival status was similar between sexes, but predictors of mortality were different between sexes.

CONCLUSIONS:

Women may be more susceptible to COPD than men. The clinical expression of COPD may differ between sexes with greater degree of hyperinflation in women, who also benefit from pulmonary rehabilitation.     

Prevalence and risk factors of development of peripheral diabetic neuropathy in type 2 diabetes mellitus in a tertiary care setting

Aims/Introduction

The study was carried out to assess the prevalence of diabetic peripheral neuropathy (DPN), compare the prevalence between known diabetes mellitus (KDM) and newly detected diabetes mellitus (NDDM), identify risk factors associated, its prevalence pattern and to assess if any sex-specific differences are present.

Materials and Methods

A cross-sectional study was carried out in a tertiary care hospital. Patients with duration of diabetes ≤6 months were considered to be NDDM. DPN was diagnosed by the combination of more than one abnormal result of 10-g monofilament, pinprick sensations and ankle reflexes, and categorized according to the severity level using vibration perception threshold. The study included 1,637 KDM and 369 NDDM patients.

Results

A total of 586 participants were found to have DPN, accounting for 29.2% (95% confidence interval [CI] 27.2–31.2) prevalence. The higher prevalence was observed in KDM compared with NDDM 33.7% (95% CI 31.42–36.01) vs 9.2% (95% CI 6.3–12.2; P < 0.001). Prevalence of mild, moderate, and severe neuropathies was 8.06, 14.55 and 6.63%, respectively. Regression analysis showed age (P < 0.001), duration of diabetes (P < 0.001), dyslipidemia (P = 0.03), glycated hemoglobin (P < 0.001), the presence of other microvascular complications (P < 0.001), macrovascular complications (P = 0.003) and alcoholic status (P < 0.033) to be associated. No sex-specific differences were observed in the mean age at diagnosis of diabetes, mean age at the diagnosis of neuropathy, and duration taken for the DPN development among females and males.

Conclusions

The study showed a high prevalence (29.2%) of DPN among north Indian type 2 diabetes mellitus patients. Thus, timely screening with earlier detection and intervention would be useful in preventing the progression of neuropathy.     

Association between glycemic control and birthweight with glycated albumin in Chinese women with gestational diabetes mellitus

Aims/Introduction

To assess glycated albumin (GA) as a potential glycemic index in managing gestational diabetes mellitus (GDM).

Materials and Methods

Eligible pregnant women were divided into the GDM group with abnormal result on a 75‐g oral glucose tolerance test (OGTT) and the control (normal) group. GA measurements, Pearson''s correlation analysis, multiple logistic regression and receiver operating characteristic curve analysis were obtained at the follow‐up examination of participants in the two groups.

Results

A total of 2,118 women were assigned to the GDM group (n = 639) and control group (n = 1,479). The mean level of serum GA in GDM group was significantly greater than that in the control group at both 24–28 and 36–38 weeks of gestation (P < 0.05). The area under the receiver operating characteristic curve for GA defining good glycemic control in GDM was 0.874 (95% confidence interval 0.811–0.938). The cut‐off point for the GA levels derived from the receiver operating characteristic curve was 11.60%, which had sensitivity and specificity for detecting a poor glycemic status of 75.93% and 86.36%, respectively. The risk of birthweight ≥3,500 g and macrosomia increased significantly with GA levels ≥13.00% at 24–28 weeks and ≥12.00% at 36–38 weeks of gestation.

Conclusions

GA might be an appropriate and conveniently measured index that can detect poor glycemic control and predict birthweights in GDM women.     

Impact of the metabolic syndrome on aortic pulse pressure and ascending aortic pulsatility in patients with angiographically normal coronary arteries

BACKGROUND:

Large artery stiffness is a major determinant of pulse pressure (PP), and PP at baseline has been associated with future coronary events.

OBJECTIVE:

To evaluate the impact of the metabolic syndrome on aortic PP and ascending aortic pulsatility (AP) in patients with angiographically normal coronary arteries.

METHODS:

Forty-two patients with the metabolic syndrome and 40 age-matched control subjects without the metabolic syndrome were included in the study. All subjects had normal coronary arteries. Diagnosis of the metabolic syndrome was based on the International Diabetes Federation guidelines published in 2005. Ascending AP was estimated as the ratio of aortic PP to mean blood pressure.

RESULTS:

Aortic PP (59±12 mmHg versus 43±10 mmHg; P<0.001) and ascending AP (0.54±0.10 versus 0.48±0.10; P<0.001) were significantly higher in the metabolic syndrome group. Multiple regression analysis revealed statistically independent relationships between ascending AP and fasting blood glucose, waist circumference and systolic blood pressure (model R²=0.408; P<0.001). The metabolic syndrome, as a whole, was also independently associated with both ascending AP (P<0.01) and aortic PP (P<0.01).

CONCLUSION:

The data showed that the metabolic syndrome is independently associated with increased aortic PP and ascending AP in patients with normal coronary arteries, suggesting aortic stiffness as one of the possible mechanisms underlying the excess cardiovascular risk associated with the metabolic syndrome.     

Predictability of 1‐h postload plasma glucose concentration: A 10‐year retrospective cohort study

Aims/Introduction

Elevated 1-h postload plasma glucose concentration (1hPG) during oral glucose tolerance test has been linked to an increased risk of type 2 diabetes and a poorer cardiometabolic risk profile. The present study analyzed the predictability and cut-off point of 1hPG in predicting type 2 diabetes in normal glucose regulation (NGR) subjects, and evaluated the long-term prognosis of NGR subjects with elevated 1hPG in glucose metabolism, kidney function, metabolic states and atherosclerosis.

Materials and Methods

A total of 116 Han Chinese classified as NGR in 2002 at the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China, were investigated. Follow-up was carried out in 2012 to evaluate the progression of glucose metabolism, kidney function, metabolic syndrome and carotid atherosclerosis.

Results

The areas under receiver operating characteristic curves were higher for 1hPG than FPG or 2hPG (0.858 vs 0.806 vs 0.746). The cut-off value of 1hPG with the maximal sum of sensitivity and specificity in predicting type 2 diabetes in NGR subjects was 8.85 mmol/L. The accumulative incidence of type 2 diabetes in subjects with 1hPG ≥8.85 mmol/L was higher than those <8.85 mmol/L (46.2% vs 3.3%, P = 0.000; relative risk 13.846, 95% confidence interval 4.223–45.400). On follow up, the prevalence of metabolic syndrome and abnormal carotid intima-media thickness in the subjects with 1hPG ≥8.85 mmol/L tended to be higher compared with those <8.85 mmol/L.

Conclusions

1hPG is a good predictor of type 2 diabetes in NGR subjects, and the best cut-off point is 8.85 mmol/L. Some tendency indicates that NGR subjects with 1hPG ≥8.85 mmol/L are more prone to metabolic syndrome and carotid atherosclerosis.     

Admission hyperglycemia predicts poorer short‐ and long‐term outcomes after primary percutaneous coronary intervention for ST‐elevation myocardial infarction

Aims/Introduction

Admission hyperglycemia is associated with poor outcome in patients with myocardial infarction. The present study evaluated the relationship between admission glucose level and other clinical variables in patients with ST‐elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI).

Materials and Methods

The 959 consecutive STEMI patients undergoing primary PCI were divided into five groups based on admission glucose levels of <100, 100–139, 140–189, 190–249 and ≥250 mg/dL. Their short‐ and long‐term outcomes were compared.

Results

Higher admission glucose levels were associated with significantly higher in‐hospital morbidity and mortality, the overall mortality rate at follow up, and the incidence of reinfarction or heart failure requiring admission or leading to mortality at follow up. The odds ratios (95% confidence interval) for in‐hospital morbidity, in‐hospital mortality, mortality at follow up and re‐infarction or heart failure or mortality at follow up of patients with admission glucose levels ≥190 mg/dL, compared with those with admission glucose levels <190 mg/dL, were 2.12 (1.3–3.4, P = 0.001), 2.74 (1.4–5.5, P = 0.004), 2.52 (1.2–5.1, P = 0.01) and 1.70 (1.03–2.8, P = 0.04), respectively. Previously non‐diabetic patients with admission glucose levels ≥250 mg/dL had significantly higher in‐hospital morbidity or mortality (44 vs 70%, P = 0.03). Known diabetic patients had higher rates of reinfarction, heart failure or mortality at follow up in the 100–139 mg/dL (8 vs 27%, P = 0.04) and 140–189 mg/dL (11 vs 26%, P = 0.02) groups.

Conclusions

Admission hyperglycemia, especially at glucose levels ≥190 mg/dL, is a predictor of poor prognosis in STEMI patients undergoing primary PCI.     

Efficacy and safety of linagliptin monotherapy in Asian patients with inadequately controlled type 2 diabetes mellitus: A multinational, 24‐week,randomized, clinical trial

Aims/Introduction

Asian patients represent a large portion of the global population with type 2 diabetes mellitus, but are underrepresented in trials of glucose-lowering therapies. The present randomized, phase III, placebo-controlled, double-blind, 24-week study evaluated the dipeptidyl peptidase-4 inhibitor, linagliptin, as monotherapy in Asian patients with inadequately controlled type 2 diabetes mellitus.

Materials and Methods

Patients who were treatment naïve or had been treated with one oral antidiabetes drug were randomized to either linagliptin 5 mg daily or a placebo after washout. The primary end-point was a change from baseline in glycated hemoglobin after 24 weeks.

Results

A total of 300 Asian (87% Chinese) patients with type 2 diabetes mellitus were randomized to linagliptin or placebo at a 2:1 ratio. After 24 weeks of treatment, adjusted mean (standard error) glycated hemoglobin decreased by a placebo-corrected −0.50 ± 0.11 (P < 0.0001). In patients with baseline glycated hemoglobin ≥8.5%, the placebo-corrected decrease in glycated hemoglobin was −0.91 ± 0.20% (P < 0.0001). Adverse events occurred in 28.0 and 28.3% of linagliptin and placebo patients, respectively, but few were drug-related (3.0 and 2.0%, respectively). Hypoglycemia was reported by one linagliptin patient and no placebo patients. Treatment with linagliptin was weight neutral.

Conclusions

In Asian patients with inadequately controlled type 2 diabetes mellitus, linagliptin 5 mg as monotherapy was efficacious and well tolerated over 24 weeks.     

Empathy Training for Resident Physicians: A Randomized Controlled Trial of a Neuroscience-Informed Curriculum

Background

Physician empathy is an essential attribute of the patient–physician relationship and is associated with better outcomes, greater patient safety and fewer malpractice claims.

Objective

We tested whether an innovative empathy training protocol grounded in neuroscience could improve physician empathy as rated by patients.

Design

Randomized controlled trial.

Intervention

We randomly assigned residents and fellows from surgery, medicine, anesthesiology, psychiatry, ophthalmology, and orthopedics (N = 99, 52% female, mean age 30.6 ± 3.6) to receive standard post-graduate medical education or education augmented with three 60-minute empathy training modules.

Main Measure

Patient ratings of physician empathy were assessed within one-month pre-training and between 1–2 months post-training with the use of the Consultation and Relational Empathy (CARE) measure. Each physician was rated by multiple patients (pre-mean = 4.6 ± 3.1; post-mean 4.9 ± 2.5), who were blinded to physician randomization. The primary outcome was change score on the patient-rated CARE.

Key Results

The empathy training group showed greater changes in patient-rated CARE scores than the control (difference 2.2; P = 0.04). Trained physicians also showed greater changes in knowledge of the neurobiology of empathy (difference 1.8; P < 0.001) and in ability to decode facial expressions of emotion (difference 1.9; P < 0.001).

Conclusions

A brief intervention grounded in the neurobiology of empathy significantly improved physician empathy as rated by patients, suggesting that the quality of care in medicine could be improved by integrating the neuroscience of empathy into medical education.KEY WORDS: empathy, randomized controlled trial, communication skills, graduate medical education, patient–physician relationship     

Referrals in acute coronary events for CARdiac catheterization: The RACE CAR trial

BACKGROUND:

Women with acute coronary syndromes have lower rates of cardiac catheterization (CC) than men.

OBJECTIVE:

To determine whether sex/gender, age, risk level and patient preference influence physician decision making to refer patients for CC.

METHODS:

Twelve clinical scenarios controlling for sex/gender, age (55 or 75 years of age), Thrombolysis in Myocardial Infarction risk score (low, moderate or high) and patient preference for CC (agreeable or refused/no preference expressed) were designed. Scenarios were administered to specialists across Canada using a web-based computerized survey instrument. Questions were standardized using a five-point Likert scale ranging from 1 (very unlikely to benefit from CC) to 5 (very likely to benefit from CC). Outcomes were assessed using a two-tailed mixed linear regression model.

RESULTS:

Of 237 scenarios, physicians rated men as more likely to benefit from CC than women (mean [± SE] 4.44±0.07 versus 4.25±0.07, P=0.03), adjusted for age, risk and patient preference. Low-risk men were perceived to benefit more than low-risk women (4.20±0.13 versus 3.54±0.14, P<0.01), and low-risk younger patients were perceived to benefit more than low-risk older patients (4.52±0.17 versus 3.22±0.16, P<0.01). Regardless of risk, patients who agreed to CC were perceived as more likely to benefit from CC than patients who were disagreeable or made no comment at all (5.0±0.23, 3.67±0.21, 2.95±0.14, respectively, P<0.01).

CONCLUSION:

Canadian specialists’ decisions to refer patients for CC appear to be influenced by sex/gender, age and patient preference in clinical scenarios in which cardiac risk is held constant. Future investigation of possible age and sex/gender biases as proxies for risk is warranted.     

A Randomized Trial of Peer Coach and Office Staff Support to Reduce Coronary Heart Disease Risk in African-Americans with Uncontrolled Hypertension

OBJECTIVE

Adopting features of the Chronic Care Model may reduce coronary heart disease risk and blood pressure in vulnerable populations. We evaluated a peer and practice team intervention on reduction in 4-year coronary heart disease risk and systolic blood pressure.

DESIGN AND SUBJECTS

A single blind, randomized, controlled trial in two adjacent urban university-affiliated primary care practices. Two hundred eighty African-American subjects aged 40 to 75 with uncontrolled hypertension.

INTERVENTION

Three monthly calls from trained peer patients with well-controlled hypertension and, on alternate months, two practice staff visits to review a personalized 4-year heart disease risk calculator and slide shows about heart disease risks. All subjects received usual physician care and brochures about healthy cooking and heart disease.

MAIN MEASURES

Change in 4-year coronary heart disease risk (primary) and change in systolic blood pressure, both assessed at 6 months.

KEY RESULTS

At baseline, the 136 intervention and 144 control subjects’ mean 4-year coronary heart disease risk did not differ (intervention = 5.8 % and control = 6.4 %, P = 0.39), and their mean systolic blood pressure was the same (140.5 mmHg, p = 0.83). Endpoint data for coronary heart disease were obtained for 69 % of intervention and 82 % of control subjects. After multiple imputation for missing endpoint data, the reduction in risk among all 280 subjects favored the intervention, but was not statistically significant (difference −0.73 %, 95 % confidence interval: -1.54 % to 0.09 %, p = 0.08). Among the 247 subjects with a systolic blood pressure endpoint (85 % of intervention and 91 % of control subjects), more intervention than control subjects achieved a >5 mmHg reduction (61 % versus 45 %, respectively, p = 0.01). After multiple imputation, the absolute reduction in systolic blood pressure was also greater for the intervention group (difference −6.47 mmHg, 95 % confidence interval: −10.69 to −2.25, P = 0.003). One patient died in each study arm.

CONCLUSIONS

Peer patient and office-based behavioral support for African-American patients with uncontrolled hypertension did not result in a significantly greater reduction in coronary heart disease risk but did significantly reduce systolic blood pressure.KEY WORDS: coronary heart disease, hypertension, African American, peer support     

The relationship between the frequency of self‐monitoring of blood glucose and glycemic control in patients with type 1 diabetes mellitus on continuous subcutaneous insulin infusion or on multiple daily injections

Aims/Introduction

We investigated the relationship between the frequency of self-monitoring of blood glucose (SMBG) and glycemic control in type 1 diabetes mellitus patients on continuous subcutaneous insulin infusion (CSII) or on multiple daily injections (MDI) using data management software.

Materials and Methods

We recruited 148 adult type 1 diabetes mellitus patients (CSII n = 42, MDI n = 106) and downloaded their SMBG records to the MEQNET™ SMBG Viewer software (Arkray Inc., Kyoto, Japan). The association between the SMBG frequency and the patients'' hemoglobin A1c (HbA1c) levels was analyzed using the χ²-test and linear regression analysis was carried out to clarify their relationship.

Results

The odds ratio of achieving a target HbA1c level of <8% (63.9 mmol/mol) was significantly higher in subjects with SMBG frequencies of ≥3.5 times/day compared with those with SMBG frequencies of <3.5 times/day in the CSII group (odds ratio 7.00, 95% confidence interval 1.72–28.54), but not in the MDI group (odds ratio 1.35, 95% CI 0.62–2.93). A significant correlation between SMBG frequency and the HbA1c level was detected in the CSII group (HbA1c [%] = –0.24 × SMBG frequency [times/day] + 8.60 [HbA1c {mmol/L} = –2.61 × SMBG frequency {times/day} + 70.5], [r = –0.384, P = 0.012]), but not in the MDI group.

Conclusions

A SMBG frequency of <3.5 times per day appeared to be a risk factor for poor glycemic control (HbA1c ≥8%) in type 1 diabetes mellitus patients on CSII.     

Effects of a sodium glucose co‐transporter 2 selective inhibitor,ipragliflozin, on the diurnal profile of plasma glucose in patients with type 2 diabetes: A study using continuous glucose monitoring

Aims/Introduction

To assess the effects of sodium glucose co-transporter 2 inhibitor therapy on the pathophysiology of type 2 diabetes.

Materials and Methods

We administered ipragliflozin to 21 inpatients with type 2 diabetes for 7 days, and analyzed the diurnal profiles of plasma glucose and 3-hydroxybutyrate. A total of 21 age-, sex- and body mass index-matched diabetic patients served as controls.

Results

Continuous glucose monitoring showed that the 24-h glucose curve was shifted downward without hypoglycemia by the administration of ipragliflozin. The average glucose level was reduced from 182 ± 54 mg/dL to 141 ± 33 mg/dL (P < 0.0001). The magnitude of the reduction was highly correlated with the baseline average glucose level. Homeostasis model assessment of insulin resistance was decreased, and homeostasis model assessment of β-cell function was increased during the treatment. Urinary glucose excretion was correlated with the average glucose level both on day 0 and on day 7, although the regression line was steeper and shifted leftward on day 7. The ipragliflozin-treated patients lost more weight than the control patients (1.4 ± 0.5 vs 0.5 ± 0.6 kg, P < 0.0001). Plasma levels of 3-hydroxybutyrate were significantly increased with peaks before breakfast and before dinner. Patient age and bodyweight loss were negatively and positively correlated with the peak levels of 3-hydroxybutyrate on day 7, respectively.

Conclusions

The ipragliflozin treatment improved the 24-h glucose curve without causing hypoglycemia. The close correlation between the magnitude of glucose reduction and the baseline plasma glucose concentration suggests that the risk of hypoglycemia is likely low. It might be prudent to monitor ketone body levels in younger patients and in patients with rapid weight loss.     

Outcomes for Resident-Identified High-Risk Patients and Resident Perspectives of Year-End Continuity Clinic Handoffs

BACKGROUND

Many patients nationwide change their primary care physician (PCP) when internal medicine (IM) residents graduate. Few studies have examined this handoff.

OBJECTIVE

To assess patient outcomes and resident perspectives after the year-end continuity clinic handoff

DESIGN

Retrospective cohort

PARTICIPANTS

Patients who underwent a year-end clinic handoff in July 2010 and a comparison group of all other resident clinic patients from 2009–2011. PGY2 IM residents surveyed from 2010–2011.

MEASUREMENTS

Percent of high-risk patients after the clinic handoff scheduled for an appointment, who saw their assigned PCP, lost to follow-up, or had an acute visit (ED or hospitalization). Perceptions of PGY2 IM residents surveyed after receiving a clinic handoff.

RESULTS

Thirty graduating residents identified 258 high-risk patients. While nearly all patients (97 %) were scheduled, 29 % missed or cancelled their first new PCP visit. Only 44 % of patients saw the correct PCP and six months later, one-fifth were lost to follow-up. Patients not seen by a new PCP after the handoff were less likely to have appropriate follow-up for pending tests (0 % vs. 63 %, P < 0.001). A higher mean no show rate (NSR) was observed among patients who missed their first new PCP visit (22 % vs. 16 % NSR, p < 0.001) and those lost to follow-up (21 % vs. 17 % NSR, p = 0.019). While 47 % of residents worried about missing important data during the handoff, 47 % reported that they do not perceive patients as “theirs” until they are seen by them in clinic.

CONCLUSIONS

While most patients were scheduled for appointments after a clinic handoff, many did not see the correct resident and one-fifth were lost to follow-up. Patients who miss appointments are especially at risk of poor clinic handoff outcomes. Future efforts should improve patient attendance to their first new PCP visit and increase PCP ownership.

Electronic supplementary material

The online version of this article (doi:10.1007/s11606-012-2100-y) contains supplementary material, which is available to authorized users.KEY WORDS: outpatient handoffs, signout, resident continuity clinic, year-end transfer, transitions of care     

Role of elevated serum uric acid levels at the onset of overt nephropathy in the risk for renal function decline in patients with type 2 diabetes

Aims/Introduction

Despite the use of intensive therapies, declining renal function is often observed during the overt nephropathy stage of type 2 diabetes. We aimed at investigating the role of serum uric acid (SUA) levels at the onset of overt nephropathy in the risk of renal function decline in type 2 diabetes patients.

Materials and Methods

The present cohort study included 290 type 2 diabetes patients who were followed from the onset of overt nephropathy. The relationship between SUA and declining renal function was assessed using Cox regression models after adjusting for known risk factors.

Results

Over a median 4.8-year follow-up period, 85 patients (4.9/100 person-years) showed serum creatinine (Cr) doubling with a total cumulative incidence of 71.9% at 20 years of follow up. The highest SUA tertile resulted in significantly a higher incidence (7.7/100 person-years) and cumulative incidence at 20 years (85.7%) than the middle (3.9/100 person-years, 54.2%) and lowest (3.0/100 person-years, 55.5%) tertiles. The univariate Cox hazard model resulted in significant risks for Cr doubling related to female sex, short diabetes duration, smoking and elevated levels of low-density lipoprotein cholesterol (LDL-c), glycated hemoglobin and SUA tertiles. SUA tertiles remained statistically significant in the multivariate model (highest vs lowest hazard ratio 2.68, 95% confidence interval 1.48−5.00, P = 0.0009).

Conclusions

Elevated SUA levels within the normal range (men >6.3 mg/dL, women >5.1) at the onset of overt nephropathy resulted in an increased risk for declining renal function in type 2 diabetes patients.