Lower Glycated Hemoglobin Levels Research Articles

Factors Contributing to Coronary Microvascular Dysfunction in Patients with Angina and Non-Obstructive Coronary Artery Disease.

Coronary microvascular dysfunction (CMD), characterised by a reduced coronary flow reserve (CFR) or an increased index of microcirculatory resistance (IMR), has received considerable attention as a cause of chest pain in recent years. However, the risks and causes of CMD remain unclear; therefore, effective treatment strategies have not yet been established. Heart failure or coronary artery disease (CAD) is a risk factor for CMD, with a higher prevalence among women. However, the other contributing factors remain unclear. In this study, we assessed the risk in patients with angina and non-obstructive coronary artery disease (ANOCA), excluding those with heart failure or organic stenosis of the coronary arteries. Furthermore, we analysed whether the risk of CMD differed according to component factors and sex. This study included 84 patients with ANOCA (36 men and 48 women; mean age, 63 years) who underwent coronary angiography and functional testing (CFT). The CFT included a spasm provocation test (SPT), followed by a coronary microvascular function test (CMVF). In the SPT, patients were mainly provoked by acetylcholine (ACh), and coronary spasm was defined as >90% transient coronary artery constriction on coronary angiography, accompanied by chest pain or ischaemic changes on electrocardiography. In 15 patients (18%) with negative ACh provocation, ergonovine maleate (EM) was administered as an additional provocative drug. In the CMVF, a pressure wire was inserted into the left anterior descending coronary artery using intravenous adenosine triphosphate, and the CFR and IMR were measured using previously described methods. A CFR < 2.0 or IMR ≥ 25 was indicative of CMD. The correlations between various laboratory indices and CMD and its components were investigated, and logistic regression analysis was performed, focusing on factors where p < 0.05. Of the 84 patients, a CFR < 2.0 was found in 22 (26%) and an IMR ≥ 25 in 40 (48%) patients, with CMD identified in 46 (55%) patients. CMD was correlated with smoking (p = 0.020) and the use of EM (p = 0.020). The factors that correlated with a CFR < 2.0 included the echocardiograph index E/e' (p = 0.013), which showed a weak but positive correlation with the CFR (r = 0.268, p = 0.013). Conversely, the factors correlated with an IMR ≥ 25 included RAS inhibitor usage (p = 0.018) and smoking (p = 0.042). Assessment of the risk of CMD according to sex revealed that smoking (p = 0.036) was the only factor associated with CMD in men, whereas the left ventricular mass index (p = 0.010) and low glycated haemoglobin levels (p = 0.012) were associated with CMD in women. Our results indicated that smoking status and EM use were associated with CMD. The risk of CMD differed between the two CMD components and sex. Although these factors should be considered when treating CMD, smoking cessation remains important. In addition, CMD assessment should be performed carefully when EM is used after ACh provocation. Further validation of our findings using prospective studies and large registries is warranted.

Automated Insulin Delivery in Women with Pregnancy Complicated by Type 1 Diabetes

BackgroundHybrid closed-loop insulin therapy has shown promise for management of type 1 diabetes during pregnancy; however, its efficacy is unclear.MethodsIn this multicenter, controlled trial, we randomly assigned pregnant women with type 1 diabetes and a glycated hemoglobin level of at least 6.5% at nine sites in the United Kingdom to receive standard insulin therapy or hybrid closed-loop therapy, with both groups using continuous glucose monitoring. The primary outcome was the percentage of time in the pregnancy-specific target glucose range (63 to 140 mg per deciliter [3.5 to 7.8 mmol per liter]) as measured by continuous glucose monitoring from 16 weeks’ gestation until delivery. Analyses were performed according to the intention-to-treat principle. Key secondary outcomes were the percentage of time spent in a hyperglycemic state (glucose level >140 mg per deciliter), overnight time in the target range, the glycated hemoglobin level, and safety events.ResultsA total of 124 participants with a mean (±SD) age of 31.1±5.3 years and a mean baseline glycated hemoglobin level of 7.7±1.2% underwent randomization. The mean percentage of time that the maternal glucose level was in the target range was 68.2±10.5% in the closed-loop group and 55.6±12.5% in the standard-care group (mean adjusted difference, 10.5 percentage points; 95% confidence interval [CI], 7.0 to 14.0; P<0.001). Results for the secondary outcomes were consistent with those of the primary outcome; participants in the closed-loop group spent less time in a hyperglycemic state than those in the standard-care group (difference, −10.2 percentage points; 95% CI, −13.8 to −6.6); had more overnight time in the target range (difference, 12.3 percentage points; 95% CI, 8.3 to 16.2), and had lower glycated hemoglobin levels (difference, −0.31 percentage points; 95% CI, −0.50 to −0.12). Little time was spent in a hypoglycemic state. No unanticipated safety problems associated with the use of closed-loop therapy during pregnancy occurred (6 instances of severe hypoglycemia, vs. 5 in the standard-care group; 1 instance of diabetic ketoacidosis in each group; and 12 device-related adverse events in the closed-loop group, 7 related to closed-loop therapy).ConclusionsHybrid closed-loop therapy significantly improved maternal glycemic control during pregnancy complicated by type 1 diabetes. (Funded by the Efficacy and Mechanism Evaluation Program; AiDAPT ISRCTN Registry number, ISRCTN56898625.)

Time-dependent effect of GLP-1 receptor agonists on cardiovascular benefits: a real-world study

BackgroundGlucagon-like peptide-1 receptor agonists (GLP-1 RAs) have shown cardiovascular benefits in cardiovascular outcome trials in type 2 diabetes mellitus. However, the most convincing evidence was obtained in subjects with established cardiovascular (CV) disease. We analyzed the determinants of GLP-1 RA-mediated CV protection in a real-world population of persons with type 2 diabetes with and without a history of CV events with long-term follow-up.MethodsRetrospective cohort study of 550 individuals with type 2 diabetes (395 in primary CV prevention, 155 in secondary CV prevention), followed at a single center after the first prescription of a GLP-1 RA between 2009 and 2019. CV and metabolic outcomes were assessed.ResultsMedian duration of follow-up was 5.0 years (0.25–10.8) in primary prevention and 3.6 years (0–10.3) in secondary prevention, with a median duration of treatment of 3.2 years (0–10.8) and 2.5 years (0–10.3) respectively. In the multivariable Cox regression model considering GLP-1 RA treatment as a time-dependent covariate, in the primary prevention group, changes in BMI and glycated hemoglobin did not have an impact on MACE risk, while age at the time of GLP-1 initiation (HR 1.08, 95% CI 1.03–1.14, p = 0.001) and GLP-1 RA cessation by time (HR 3.40, 95% CI 1.82–6.32, p < 0.001) increased the risk of MACE. Regarding the secondary prevention group, only GLP-1 RA cessation by time (HR 2.71, 95% CI 1.46–5.01, p = 0.002) increased the risk of MACE. With respect to those who withdrew treatment, subjects who continued the GLP-1 RA had significantly greater weight loss and lower glycated hemoglobin levels during follow-up.ConclusionsIn this real-world type 2 diabetes population, discontinuation of GLP-1 RA treatment was associated to a higher risk of major cardiovascular events, in both subjects with and without a history of CV events.

Comparison of cardiovascular and renal outcomes between dapagliflozin and empagliflozin in patients with type 2 diabetes without prior cardiovascular or renal disease.

BackgroundCardiovascular and renal benefits of sodium glucose co-transporter 2 inhibitors (SGLT2i) have been clearly demonstrated. However, studies comparing the effects of dapagliflozin and empagliflozin are scarce. In addition, relatively few studies have analyzed the effects of SGLT2i in diabetic patients without established atherosclerotic cardiovascular disease (ASCVD), chronic kidney disease (CKD), or heart failure (HF), and current guidelines recommend SGLT2i and other antidiabetic drugs equally in this population. Therefore, we aimed to compare the clinical outcomes between dapagliflozin, empagliflozin, and dipeptidyl peptidase-4 inhibitors (DPP4i) in patients with type 2 diabetes without prior ASCVD, CKD, or HF.MethodsUsing a propensity-score matching method, we retrospectively analyzed 921 patients treated with dapagliflozin, 921 patients treated with empagliflozin, and 1842 patients treated with DPP4i (control group). Study outcomes comprised composite coronary events (acute coronary syndrome and coronary revascularization), composite ischemic events (coronary events and stroke), and composite heart failure and renal events.ResultsDuring follow up (median, 43.4 months), the incidence of composite coronary events was significantly lower in the SGLT2i groups than in the control group, and the incidence of composite ischemic events was lower in the dapagliflozin group than in the control group. Dapagliflozin and empagliflozin both demonstrated significant benefits in terms of HF and renal outcomes, supported by renoprotective effects, as assessed by the change in glomerular filtration rate. At 24–36 months of treatment, the empagliflozin group had higher low-density lipoprotein cholesterol levels, and lower glycated hemoglobin levels, compared to those in the dapagliflozin and control groups.ConclusionSGLT2i use was associated with a significantly reduced risk of ASCVD, HF hospitalization, and renal events, compared to that with DPP4i use among diabetic patients without prior ASCVD, CKD, or HF. There were no significant differences in clinical outcomes between dapagliflozin and empagliflozin, supporting a SGLT2i class effect.

Sex Differences in TB Clinical Presentation, Drug Exposure, and Treatment Outcomes in India

The role of sex differences in clinical presentation, TB drug pharmacokinetic variables, and treatment outcomes is unclear. What is the effect of sex on TB disease severity, drug exposure, and treatment outcome? This study was a prospective cohort study conducted in India. It assessed TB disease severity; risk of unfavorable treatment outcomes (failure, recurrence, and death) according to sex; and risk factors for unfavorable outcomes stratified according to sex. Effects of sex on the pharmacokinetic variables (maximum concentration and area under the curve) of rifampicin, isoniazid, and pyrazinamide were estimated by using noncompartmental analyses. Of 1,541 people with microbiologically confirmed TB, 567 (37%) were women. Women had a lower risk of high mycobacterial burden (smear grade≥ 2 and/or time to detection< 7days) with an adjusted OR of 0.70 (95%CI, 0.56-0.87). Among the 744 participants who were followed up prospectively, 261 (35%) were women. Women had a lower risk of unfavorable treatment outcomes (adjusted incidence risk ratio, 0.60; 95%CI, 0.43-0.85), mostly because recurrence was lower (adjusted incidence risk ratio, 0.45; 95%CI, 0.23-0.86). Isoniazid (but not rifampicin and pyrazinamide) maximum concentration and area under the curve were significantly higher among women (P< .01) than men. Among women, unfavorable outcomes were more likely among those with cavitary disease, but among men, increased risk of unfavorable outcomes was associated with alcohol use, higher BMI, and lower glycated hemoglobin level. Women present with lower mycobacterial burden, achieve higher TB drug exposure, and are less likely to have unfavorable treatment outcomes than men. Strategies to improve TB treatment success should take into account sex differences in risk factors for unfavorable outcomes.

New Onset Autoimmune Diabetes Mellitus, Autoimmune Thyroiditis and Subsequent Autoimmune Hepatitis With Monoclonal Antibody to Programmed Cell Death-1 (PD-1) Protein Therapy in a Patient With Non Small Cell Lung Cancer: 18 Months Follow up Experience

Background: Monoclonal antibody to Programmed cell death-1 (PD-1) protein binds to PD-1 receptor and blocks its interaction with PD Ligand 1 and PD Ligand 2, which helps restore the immune response for various types of cancer treatment are used widely. These agents are associated with many auto immune diseases. We describe a case where a patient treated with PD-1 inhibitor manifested three autoimmune diseases. Clinical Case: A 62 year old female with past medical history of Non small cell adenocarcinoma stage IV with gluteal muscle metastasis was referred to endocrinology for new onset Diabetes Mellitus (DM). Family history was negative for thyroid and other autoimmune diseases, Her brother had type 2 DM. On physical examination: elderly female, thin built, BMI: 16.7 kg/m2 with a non-palpable thyroid and no skin lesions. Patient was started on Pembrolizumab every 3 weeks. During 2nd cycle, her basic metabolic panel revealed blood glucose level of 409 mg/dl, negative serum ketone, normal anion gap of 11 and HbA1c: 7.0 %, Anti TPO: positive; 9 (ref<9 IU/mL) with normal TSH, Ft4 and T3 level. C-peptide level was <0.1 (ref: 0.8- 3.85); Glutamic acid (GAD) antibody elevated: >250 (ref range<5), and Islet Cell Antibody was negative. CT scan of abdomen with contrast showed pancreas within normal limit. Prior to initiation of Pembrolizumab therapy her HbA1C was 5.3 and 8 am serum cortisol level was 19 ug/dl. She was started on multiple dose of subcutaneous insulin therapy for autoimmune DM. Her DM was well controlled on .77 units/ kg insulin dosage targeting a finger stick of 140–200 mg%. Following 16 cycles of Pembrolizumab patient was found to have elevated liver enzymes ALT 807 U/L, AST 1109 U/L, total bilirubin 2.1 mg/dL, with concerns for autoimmune hepatitis. A CT scan with contrast ruled out any metastatic lesion to liver, follow up labs with HbA1c 12.3%, TSH 1.09 uIU/mL, C-peptide remains<0.01 and TPO Ab remains positive: 60 IU/mL. Patient’s HLA pattern was heterozygous DR4-DQ8 and heterogyzous DR1-DQ5 haplotype. Conclusion: The loss of β cell function in our case appeared to be fulminant as suggested by the relatively low glycated hemoglobin level while C-peptide level was undetectable at diagnosis of autoimmune DM. High dose steroid therapy was not successful in reversing the condition and another case reported beta cell destruction was halted by stopping the check point inhibitor therapy. Recently, American society of Oncology article suggested measuring glucose at baseline and with each treatment cycle during induction for 12 weeks, then every 3–6 weeks thereafter risk factors for each subtype of DM to be assessed[1]. Reference: 1. Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: American Society of Clinical Oncology Clinical Practice Guideline, Journal of Clinical Oncology 2018 36:17, 1714–1768, DOI: 10.1200/JCO.2017.77.6385

Differences in initial versus recurrent diabetic foot ulcers at a specialized tertiary diabetic foot care center in China.

ObjectiveTo investigate the characteristics of diabetic foot ulcer (DFU) recurrence.MethodsA total of 573 patients with DFUs were recruited and divided into an initial group (395 patients) and a recurrence group (178 patients). The factors related to recurrence were analyzed using multivariate regression.ResultsThe recurrence group had longer diabetes duration (odds ratio [OR] 192; 95% confidence interval 120, 252 vs. 156; 96, 240); lower glycated hemoglobin levels (OR 8.1; 95% CI 6.8, 9.6 vs. 9.1; 7.4, 10.5), and higher rates than the initial group of amputation (37.5% vs. 2.0%), history of vascular intervention (21.3% vs. 3.9%), retinopathy (77.7% vs. 64.7%), callus (44.4% vs. 20.8%), foot deformity (51.2% vs. 24.6%), and outdoor sports shoe wearing (34.0% vs. 21.2%). Multiple factor logistic regression analysis showed that diabetes duration (OR 1.004), callus (OR 2.769), vascular intervention (OR 2.824) and amputation (OR 22.256) were independent risk factors for DFU recurrence.ConclusionDiabetes duration, callus, history of vascular intervention, and amputation were independent risk factors for recurrent DFUs in a cohort of Chinese patients with active DFU. The prevention and treatment of DFUs, especially callus treatment, foot care, and blood glucose control, should be improved in China.

Pembrolizumab-induced fulminant type 1 diabetes with C-peptide persistence at first referral.

SummaryA 72-year-old man with no history of diabetes was referred to our department due to hyperglycemia during pembrolizumab treatment for non-small-cell lung carcinoma. His blood glucose level was 209 mg/dL, but he was not in a state of ketosis or ketoacidosis. Serum C-peptide levels persisted at first, but gradually decreased, and 18 days later, he was admitted to our hospital with diabetic ketoacidosis (DKA). The patient was diagnosed with fulminant type 1 diabetes (FT1D) induced by pembrolizumab. According to the literature, the insulin secretion capacity of a patient with type 1 diabetes (T1D) induced by anti-programmed cell death-1 (anti-PD-1) antibody is depleted in approximately 2 to 3 weeks, which is longer than that of typical FT1D. Patients with hyperglycemia and C-peptide persistence should be considered for hospitalization or frequent outpatient visits with insulin treatment because these could indicate the onset of life-threatening FT1D induced by anti-PD-1 antibodies. Based on the clinical course of this patient and the literature, we suggest monitoring anti-PD-1 antibody-related T1D.Learning points:Immune checkpoint inhibitors, such as anti-PD-1 antibodies, are increasingly used as anticancer drugs. Anti-PD-1 antibodies can cause immune-related adverse events, including T1D.FT1D, a novel subtype of T1D, is characterized by the abrupt onset of hyperglycemia with ketoacidosis, a relatively low glycated hemoglobin level and depletion of C-peptide level at onset.In patients being treated with anti-PD-1 antibody, hyperglycemia with C-peptide level persistence should be monitored through regular blood tests. Because of C-peptide persistence and mild hyperglycemia, it is possible to miss a diagnosis of life-threatening FT1D induced by anti-PD-1 antibody.In particular, in patients who have no history of diabetes, hyperglycemia without DKA is likely to be the very beginning of anti-PD-1 antibody-induced T1D. Therefore, such patients must be considered for either hospitalization or frequent outpatient visits with insulin injections and self-monitoring of blood glucose.

A Randomized Trial of Alerting to Low Glycated Hemoglobin Level in Older Adults: Results of the Low Indexes of Metabolism Intervention Trial B (LIMIT-B)

ObjectivesThe benefit of alerting clinical staff to low plasma glycated hemoglobin (HbA1c) in patients aged 75 years and older who receive antidiabetic drugs remains uncertain. Design, Setting, and ParticipantsIn a randomized controlled trial, 1684 patients with HbA1c ≤ 6.5% who received antidiabetic drugs were assigned to have an e-mail alert sent to their physician, and 1643 were assigned to have no such alert (control group). The primary outcome of the trial was annual death. Secondary outcomes included antidiabetic drug dose reduction and HbA1c change. ResultsIn the first quarter, antidiabetic drug-defined daily doses were reduced on average by 10.4 ± 35.8 (16% ± 55%) in the intervention group and by 6.4 ± 36.1 (10% ± 56%) in the control group (difference −4.1 ± 1.2, 95% confidence interval [CI] −6.5 to −1.6; P = .001). Measured HbA1c levels were raised by a mean (± standard deviation) of 0.28 ± 0.77 in the intervention group and by 0.18 ± 0.57 in the control group (difference 0.10 ± 0.02, 95% CI –0.15 to −0.059, P < .001). One year after the alerts, 121 patients (7.2%) died in the intervention group and 107 patients (6.5%) died in the control group (relative risk 1.1, 95% CI 0.86-1.42; P = .44). Conclusions and ImplicationsIn this trial, alerting clinical staff to low HbA1c in patients aged 75 years and older treated with antidiabetic medicines was associated with mildly reduced antidiabetic doses and increased HbA1c but was not associated with a significant difference in survival rate compared with usual clinical care.

The attitude of patients with types 1 and 2 diabetes mellitus towards having the disease

To analyze the types of attitude towards disease, their relationships to its course in patients with diabetes mellitus (DM). 418 patients with DM, including 318 with type 2 DM (T2DM) and 100 with Type 1 (T1DM), were examined. Clinical and laboratory examinations were performed; the types of attitude towards the disease were studied. The patients with T2DM were more frequently found to have anxious (12.9%) and hypochondriacal (10.7%) types of attitude towards the disease; those with T1DM had euphoric types. The paranoiac type of disease attitude, which was characterized by the presence of peculiar notions about the disease, was detected in 15.1% of the patients with T2DM and in 13% of those with T1DM. Hypernosognosia (overreaction to disease) was more often identified in T2DM (62.3% versus 39% in T1DM (χ2; p < 0.001). In the T2DM group, hypernosognosia was more frequently seen in women, unemployed persons, and obese patients. With the comparable awareness about the disease and degree of self-control, the patients with T2DM with no signs of hypernosognosia had a lower glycated hemoglobin level [7.35 (6.6; 8.6)%] than those with hypernosognosia [7.9 (7; 9.4)%] (p = 0.024). The revealed peculiarities of attitude towards the disease in patients with DM justify the need for increased attention to their psychological characteristics. The situation could be improved if the physicians are be informed, the time of outpatient care is prolonged, and psychotherapists and/or clinical psychologists are widely involved in the management of diabetic patients.

Low glycated hemoglobin level is associated with severity of frailty in Japanese elderly diabetes patients.

Aims/IntroductionPreviously, a study using a narrowly defined (physical base) frailty scale reported that both good and bad (U‐shaped curve) glycated hemoglobin (HbA1c) levels were frailty risk factors in patients with type 2 diabetes mellitus. However, no such studies in Japan have shown this. We aimed to evaluate the frailty risk factors including HbA1c in elderly Japanese patients with type 2 diabetes mellitus using a broadly defined (both physical and psychosocial base) frailty scale, the Clinical Frailty Scale (CFS).Materials and MethodsWe randomly enrolled 132 elderly patients with type 2 diabetes mellitus (aged ≥65 years) and categorized the patients into nine stages of frailty using CFS. Because no patient had CFS 9, patients with a CFS score of 1–4 and 5–8 were defined as non‐frail and frail, respectively. We attempted to identify the risk factors of frailty by investigating the association between CFS stage and various patient factors.ResultsMultiple regression analysis showed that an increase in age, low levels of albumin, high‐density lipoprotein cholesterol, systolic blood pressure, HbA1c, total cholesterol, and bodyweight were statistically significant and strong independent risk factors for frailty, suggesting that reverse metabolism owing to malnutrition in elderly type 2 diabetes mellitus patients might be involved.ConclusionsHbA1c level was not a U‐shaped risk for frailty, suggesting that relatively good glycemic control might be more important for frailty than poor control in elderly type 2 diabetes mellitus patients.

Impact of preoperative visceral fat proportion on type 2 diabetes in patients with low body mass index after gastrectomy

BackgroundMetabolic surgery is an effective option for treatment of type 2 diabetes. Although body mass index (BMI) has several limitations in differentiating the metabolic risks of the same weight of muscle and fat, it is used as the basis of indication for metabolic surgery. ObjectivesSince visceral fat is highly associated with metabolic disease, we evaluated the effectiveness of visceral fat proportion (VFP) for predicting metabolic risk preoperatively. SettingUniversity hospital. MethodsFifty-two type 2 diabetes patients with BMI≤35 kg/cm2 who underwent gastrectomy for gastric cancer were included. Pre- and postoperative VFPs were measured using abdominal computed tomography. Multivariate logistic regression analysis was performed to estimate the effect of VFP on type 2 diabetes. Receiver operating curve analysis was used to estimate the effectiveness of VFP as a predictor of type 2 diabetes improvement. ResultsThirty-three of the 52 patients (63%) showed improved type 2 diabetes postoperatively. Low preoperative VFP (odds ratio [OR] = .913; 95% confidence interval [CI] = .835–.999; P = .048) and low glycated hemoglobin level (OR = .357; 95% CI = .172–.742; P = .006) were associated with type 2 diabetes improvement 2 years after gastrectomy. The area under the curve was 70.2%, indicating moderate accuracy. ConclusionsPreoperative VFP might be a reasonable predictive factor for type 2 diabetes improvement after gastrectomy for patients with a BMI≤35 kg/cm2. High-quality studies of visceral fat for metabolic function are needed in the future.

A Prepregnancy Care Program for Women With Diabetes: Effective and Cost Saving.

Only a minority of women with diabetes attend prepregnancy care service and the economic effects of providing this service are unclear. The objective of the study was to design, put into practice, and evaluate a regional prepregnancy care program for women with types 1 and 2 diabetes. This was a prospective cohort and cost-analysis study. The study was conducted at antenatal centers along the Irish Atlantic Seaboard. Four hundred fourteen women with type 1 or 2 diabetes participated in the study. The intervention for the study was a newly developed prepregnancy care program. The program was assessed for its effect on the risk of adverse pregnancy outcomes. The difference between program delivery cost and the excess cost of treating adverse outcomes in nonattendees was evaluated. In total, 149 (36%) attended: this increased from 19% to 50% after increased recruitment measures in 2010. Attendees were more likely to take preconception folic acid (97.3% vs 57.7%, P < .001) and less likely to smoke (8.7% vs 16.6%, P = .03) or take potentially teratogenic medications at conception (0.7 vs 6.0, P = .008). Attendees had lower glycated hemoglobin levels throughout pregnancy (first trimester glycated hemoglobin 6.8% vs 7.7%, P < .001; third trimester glycated hemoglobin 6.1% vs 6.5%, P = .001), and their offspring had lower rates of serious adverse outcomes (2.4% vs 10.5%, P = .007). The adjusted difference in complication costs between those who received prepregnancy care vs usual antenatal care only is €2578.00. The average cost of prepregnancy care delivery is €449.00 per pregnancy. This regional prepregnancy care program is clinically effective. The cost of program delivery is less than the excess cost of managing adverse pregnancy outcomes.

Home Use of an Artificial Beta Cell in Type 1 Diabetes

BackgroundThe feasibility, safety, and efficacy of prolonged use of an artificial beta cell (closed-loop insulin-delivery system) in the home setting have not been established.MethodsIn two multicenter, crossover, randomized, controlled studies conducted under free-living home conditions, we compared closed-loop insulin delivery with sensor-augmented pump therapy in 58 patients with type 1 diabetes. The closed-loop system was used day and night by 33 adults and overnight by 25 children and adolescents. Participants used the closed-loop system for a 12-week period and sensor-augmented pump therapy (control) for a similar period. The primary end point was the proportion of time that the glucose level was between 70 mg and 180 mg per deciliter for adults and between 70 mg and 145 mg per deciliter for children and adolescents.ResultsAmong adults, the proportion of time that the glucose level was in the target range was 11.0 percentage points (95% confidence interval [CI], 8.1 to 13.8) greater with the use of the closed-loop system day and night than with control therapy (P<0.001). The mean glucose level was lower during the closed-loop phase than during the control phase (difference, −11 mg per deciliter; 95% CI, −17 to −6; P<0.001), as were the area under the curve for the period when the glucose level was less than 63 mg per deciliter (39% lower; 95% CI, 24 to 51; P<0.001) and the mean glycated hemoglobin level (difference, −0.3%; 95% CI, −0.5 to −0.1; P=0.002). Among children and adolescents, the proportion of time with the nighttime glucose level in the target range was higher during the closed-loop phase than during the control phase (by 24.7 percentage points; 95% CI, 20.6 to 28.7; P<0.001), and the mean nighttime glucose level was lower (difference, −29 mg per deciliter; 95% CI, −39 to −20; P<0.001). The area under the curve for the period in which the day-and-night glucose levels were less than 63 mg per deciliter was lower by 42% (95% CI, 4 to 65; P=0.03). Three severe hypoglycemic episodes occurred during the closed-loop phase when the closed-loop system was not in use.ConclusionsAmong patients with type 1 diabetes, 12-week use of a closed-loop system, as compared with sensor-augmented pump therapy, improved glucose control, reduced hypoglycemia, and, in adults, resulted in a lower glycated hemoglobin level. (Funded by the JDRF and others; AP@home04 and APCam08 ClinicalTrials.gov numbers, NCT01961622 and NCT01778348.)

Change in Albuminuria and eGFR Following Insulin Sensitization Therapy Versus Insulin Provision Therapy in the BARI 2D Study

In the Bypass Angioplasty Revascularization Investigation 2 Diabetes randomized trial, glycemic control with insulin-sensitization therapy was compared with insulin-provision therapy in patients with type 2 diabetes and coronary artery disease. This study examined differences in albumin excretion and renal function in the insulin-sensitization group versus the insulin-provision group over 5 years. In total, 1799 patients with measurements of creatinine and urine albumin/creatinine ratio at baseline and at least two follow-up visits were included. Management of BP, lipids, and lifestyle counseling was uniform. Progression of albuminuria was defined as doubling of baseline albumin/creatinine ratio to at least 100 mg/g or worsening of albumin/creatinine ratio status on two or more visits. Worsening renal function was defined as >25% decline in estimated GFR and annualized decline of >3 ml/min per 1.73 m(2) per year. By 6 months and thereafter, the mean glycated hemoglobin levels were lower in the insulin-sensitization group compared with the insulin-provision group (P<0.002 for each time point; absolute difference=0.4%). Albumin/creatinine ratio increased over time in the insulin-sensitization group (P value for trend<0.001) and was stable in the insulin-provision group. Risk for progression of albumin/creatinine ratio was higher in the insulin-sensitization group compared with the insulin-provision group (odds ratio, 1.59; 95% confidence interval, 1.25 to 2.02; P=0.02). Over 5 years, albumin/creatinine ratio increased from 11.5 (interquartile range=5.0-46.7) to 15.7 mg/g (interquartile range=6.2-55.4) in the insulin-sensitization group (P<0.001) and from 12.1 (interquartile range=5.3-41.3) to 12.4 mg/g (interquartile range=5.8-50.6) in the insulin-provision group (P=0.21). Estimated GFR declined from 75.0±20.6 to 66.3±22.6 ml/min per 1.73 m(2) in the insulin-sensitization group (P<0.001) and from 76.1±29.5 to 66.8±22.1 ml/min per 1.73 m(2) in the insulin-provision group (P<0.001). Over 5 years, despite lower glycated hemoglobin levels, the insulin-sensitization treatment group had greater progression of albumin/creatinine ratio compared with the insulin-provision treatment group. Decline in estimated GFR was similar.

Gram-Negative Diabetic Foot Osteomyelitis

Osteomyelitis frequently complicates infections in the feet of patients with diabetes. Gram-positive cocci, especially Staphylococcus aureus, are the most commonly isolated pathogens, but gram-negative bacteria also cause some cases of diabetic foot osteomyelitis (DFO). These gram-negatives require different antibiotic regimens than those commonly directed at gram-positives. There are, however, few data on factors related to their presence and how they influence the clinical picture. We conducted a retrospective study to determine the variables associated with the isolation of gram-negative bacteria from bone samples in cases of DFO and the clinical presentation of these infections. Among 341 cases of DFO, 150 had a gram-negative isolate (alone or combined with a gram-positive isolate) comprising 44.0% of all patients and 50.8% of those with a positive bone culture. Compared with gram-positive infections, wounds with gram-negative organisms more often had a fetid odor, necrotic tissue, signs of soft tissue infection accompanying osteomyelitis, and clinically severe infection. By multivariate analysis, the predictive variables related to an increased likelihood of isolating gram-negatives from bone samples were glycated hemoglobin <7% (odds ratio [OR] = 2.0, 95% confidence interval [CI] = 1.1-3.5) and a wound caused by traumatic injury (OR = 2.0, 95% CI = 1.0-3.9). Overall, patients whose bone samples contained gram-negatives had a statistically significantly higher prevalence of leukocytosis and higher white blood cell counts than those without gram-negatives. In conclusion, gram-negative organisms were isolated in nearly half of our cases of DFO and were associated with more severe infections, higher white blood cell counts, lower glycated hemoglobin levels, and wounds of traumatic etiology.

Regulation of Glycemic Control by Physical Activity: A Role for Mitochondria?

Hippocrates is attributed with stating that “... eating alone will not keep a man well; he must also take exercise. For food and exercise, while possessing opposite qualities, yet work together to produce health” (1). Those words of wisdom highlight that the benefits of physical activity for maintenance of good health, in conjunction with appropriate diet, have long been recognized. As we try to manage the worldwide increase of diabetes, it is useful to remind ourselves of the value of exercise for preventing and treating insulin resistance. For adults with type 2 diabetes, both endurance and resistive exercise can lower glycated hemoglobin levels within 3–6 months (2) and moderate-intensity walking can reduce the amplitude of postprandial glucose excursions within 5–7 days (3). In the Diabetes Prevention Program, adults at risk for developing type 2 diabetes who were placed in a weight loss plus exercise program for ∼3 years had significantly lower incidence of diabetes for up to 10 years after enrollment compared with those who received either standard of care or metformin (4). In the lifestyle intervention group, weight loss was the major determinant of diabetes prevention during the first year, but physical activity predicted weight maintenance and diabetes prevention in subsequent years (5). Thus, although there have been steady improvements in pharmaceutical treatments to improve glycemic control in individuals who are obese and/or diabetic, physical activity remains an important first-line therapeutic approach. Exercise improves glucose control by increasing insulin sensitivity and non–insulin-dependent glucose uptake in skeletal muscle (6). There is also evidence that energy turnover (i.e., the oxidation of glucose and fatty acids) during muscle contraction is important for preventing the …

Long-term Renal Outcomes of Patients With Type 1 Diabetes Mellitus and Microalbuminuria&lt;subtitle&gt;An Analysis of the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Cohort&lt;/subtitle&gt;&lt;alt-title&gt;Microalbuminuria Outcomes in Type 1 Diabetes&lt;/alt-title&gt;

Microalbuminuria is a common diagnosis in the clinical care of patients with type 1 diabetes mellitus. Long-term outcomes after the development of microalbuminuria are variable.We quantified the incidence of and risk factors for long-term renal outcomes after the development of microalbuminuria in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study. The DCCT randomly assigned 1441 persons with type 1 diabetes to intensive or conventional diabetes therapy, and participants were subsequently followed up during the observational EDIC study. During the DCCT/EDIC study, 325 participants developed incident persistent microalbuminuria (albumin excretion rate, ≥30 mg/24 h at 2 consecutive study visits). We assessed their subsequent renal outcomes, including progression to macroalbuminuria (albumin excretion rate, ≥300 mg/24 h at 2 consecutive visits), impaired glomerular filtration rate (estimated glomerular filtration rate, <60 mL/min/1.73 m(2) at 2 consecutive study visits), end-stage renal disease, and regression to normoalbuminuria (albumin excretion rate, <30 mg/24 h at 2 consecutive visits).The median follow-up period after persistent microalbuminuria diagnosis was 13 years (maximum, 23 years). Ten-year cumulative incidences of progression to macroalbuminuria, impaired glomerular filtration rate, end-stage renal disease, and regression to normoalbuminuria were 28%, 15%, 4%, and 40%, respectively. Albuminuria outcomes were more favorable with intensive diabetes therapy, lower glycated hemoglobin level, absence of retinopathy, female sex, lower blood pressure, and lower concentrations of low-density lipoprotein cholesterol and triglycerides. Lower glycated hemoglobin level, absence of retinopathy, and lower blood pressure were also associated with decreased risk of impaired glomerular filtration rate.After the development of persistent microalbuminuria, progression and regression of kidney disease each commonly occur. Intensive glycemic control, lower blood pressure, and a more favorable lipid profile are associated with improved outcomes.

Comparison of the potential for developmental toxicity of prenatal exposure to two dietary chromium supplements, chromium picolinate and [Cr3O(O2CCH2CH3)6(H2O)3]+, in mice

Chromium(III) is generally thought to be an essential trace element that allows for proper glucose metabolism. However, chromium(III) picolinate, Cr(pic)3, a popular dietary supplement form of chromium, has been shown to be capable of generating hydroxyl radicals and oxidative DNA damage in rats. The cation [Cr3O(O2CCH2CH3)(6(H2O)3]+, Cr3, has been studied as an alternative supplemental source of chromium. It has been shown to increase insulin sensitivity and lower glycated hemoglobin levels in rats, making it attractive as a potential therapeutic treatment for gestational diabetes. To date, no studies have been published regarding the safety of Cr3 supplementation to a developing fetus. From gestation days (GD) 6-17, mated CD-1 female mice were fed diets delivering either 25 mg Cr/kg/day as Cr(pic)(3), 3.3 or 26 mg Cr/kg/day as Cr3, or the diet only to determine if Cr3 could cause developmental toxicity. Dams were sacrificed on GD 17, and their litters were examined for adverse effects. No signs of maternal toxicity were observed. No decrease in fetal weight or significantly increased incidence of skeletal defects was observed in the Cr3 or Cr(pic)3 exposed fetuses compared to the controls. Maternal exposure to either Cr(pic)3 or Cr3 at the dosages employed did not appear to cause deleterious effects to the developing offspring in mice.

The effectiveness of hydroxychloroquine in patients with type 2 diabetes mellitus who are refractory to sulfonylureas—a randomized trial

Aim: To assess the glucose-lowering efficacy, responsiveness, duration of action and impact on quality-of-life of hydroxychloroquine (HXCHL), when added as an antihyperglycemic agent to patients with sulfonylurea-refractory type 2 diabetes. Methods: One hundred and thirty-five obese patients with type 2 diabetes (mean age 57.5 years) and a glycated hemoglobin (GHb) ≥11% despite maximum sulfonylureas were randomly allocated to the addition of HXCHL (up to 300 mg bid) or placebo and followed for up to 18 months. Randomization was stratified by baseline GHb (<13.5% versus ≥13.5%). The primary outcome was ‘blinded’ withdrawal of study drug due to unacceptable glycemic control; GHb, glucose tolerance, lipids, and quality of life were also assessed. Results: Those on placebo were more likely to be withdrawn from study drug because of unacceptable glycemic control than patients randomized to HXCHL (95.5 and 69.6% given placebo and HXCHL, respectively; P=0.0001). During the first 6 months, HXCHL decreased GHb by an absolute amount of 1.02% more than placebo (95% CI 0.24, 1.81). Glucose tolerance and LDL cholesterol improved during the first 3 months of therapy. No significant adverse effects were noted. Factors that predicted responsiveness included an initial GHb <13.5%, early responsiveness to study drug, and no prior metformin use. Lower GHb levels at baseline predicted a better response; the hazard of withdrawal increased 36% (95% CI 11%, 66%) for every 1% increase in GHb even in patients whose baseline GHb was <13.5%. Conclusions: HXCHL improves glycemic control in sulfonylurea-refractory patients with poorly controlled type 2 diabetes.