Autosomal Dominant, Long-Standing Dysglycemia in 2 Families with Unique Phenotypic Features.

We describe 2 families with 5 members from 2 generations whose clinical and laboratory characteristics over up to 15 years were consistent with dysglycemia/impaired glucose tolerance. In both families (2 probands and 3 family members), long-term follow-up excluded diabetes type 1 and type 2. Diabetes type 1 antibodies were persistently negative and C-peptide levels were normal. In Family 1, the proband, during a follow-up of 7 years (10.3-17.5 years of age), exhibited persistently high HbA1c (>5.7%) with fasting blood glucose levels mostly higher than 100 mg/dl and postprandial glucose levels up to 180 mg/dl. She eventually required oral anti-diabetics with an improvement in glycemic balance. The father and sister also had persistent mild hyperglycemia with borderline high HbA1c (mostly > 5.7%) levels over 15 and 6.2 years respectively. In Family 2, the proband exhibited borderline high fasting hyperglycemia (>100 mg/dl) at age 16.2 years with increasing HbA1c levels (from 5.6%-5.9%) and impaired glucose tolerance at age 18.3 years (2 h blood glucose 156 mg/dl after 75 g glucose). His sister also exhibited borderline hyperglycemia with borderline high HbA1c over 2 years (13.6-15.4 years). These subjects shared a unique phenotype. They are tall and slim with decreased BMI. Three subjects from Generation II failed to thrive during infancy. In view of the data from 2 generations suggesting maturity-onset diabetes of the young (MODY) with autosomal dominant inheritance, we sought to analyze the MODY genes. In Family 1, the molecular analysis by the MODY panel including 11 genes and whole exome sequencing did not detect any mutation in the proband. In Family 2, the MODY panel was also negative in the proband's sister. These families may represent a hitherto unidentified syndrome. Unique features described in this report may help to reveal additional families with similar characteristics and to decipher the molecular basis of this syndrome. In selected cases, oral antidiabetics in adolescents may improve the glycemic balance.

Influence of Fasting until Noon (Extended Postabsorptive State) on Clock Gene mRNA Expression and Regulation of Body Weight and Glucose Metabolism.

The trend of fasting until noon (omission or delayed breakfast) is increasingly prevalent in modern society. This eating pattern triggers discordance between endogenous circadian clock rhythms and the feeding/fasting cycle and is associated with an increased incidence of obesity and T2D. Although the underlying mechanism of this association is not well understood, growing evidence suggests that fasting until noon, also known as an "extended postabsorptive state", has the potential to cause a deleterious effect on clock gene expression and to disrupt regulation of body weight, postprandial and overall glycemia, skeletal muscle protein synthesis, and appetite, and may also lead to lower energy expenditure. This manuscript overviews the clock gene-controlled glucose metabolism during the active and resting phases and the consequences of postponing until noon the transition from postabsorptive to fed state on glucose metabolism, weight control, and energy expenditure. Finally, we will discuss the metabolic advantages of shifting more energy, carbohydrates (CH), and proteins to the early hours of the day.

Curalin supplement for patients with type 2 diabetes mellitus.

OBJECTIVE: To examine the efficacy and safety of Curalin supplement in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: Adult patients with type 2 diabetes were randomized 1:1 to receive Curalin supplement or placebo. The primary endpoint was HbA1c decrease at 1 month. The secondary endpoint was a decrease in HbA1c by more than 0.5% and 1% and a change in 7 daily blood glucose measurements. A satisfaction questionnaire was used as an exploratory endpoint. Safety variables and adverse events were assessed. RESULTS: After 1 month of intervention, HbA1c was reduced by 0.94% in the Curalin arm versus 0.4% in the placebo arm (P = 0.008). 72% of Curalin patients had decreased HbA1c levels >0.5% versus 35% in the placebo arm (P < 0.05). The Treatment Satisfaction Questionnaire indicated that Curalin arm patients reported higher overall satisfaction. CONCLUSIONS: Curalin treatment significantly reduced HbA1c over a 1-month period and was well-tolerated.

NRD.E1, an innovative non-opioid therapy for painful diabetic peripheral neuropathy-A randomized proof of concept study.

BACKGROUND: Painful diabetic peripheral neuropathy (PDPN) affects up to 26% of patients with diabetes mellitus, with major impacts on their general health and well-being. Most available drugs fail to deliver acceptable pain reduction in the majority of patients and are often poorly tolerated. NRD.E1 is a novel product that has shown anti-nociceptive preclinical effects and good tolerability in healthy volunteer studies. METHODS: This phase 2a, randomized, dose-finding, Proof of Concept study enrolled patients with PDPN of ≥3 months duration. After at least one treatment-free week (WO week), 88 patients entered a 1-week single-blind (SB)-placebo run-in period, followed by 3 weeks' double-blind (DB) treatment, during which they received NRD.E1 at 10, 40 or 150 mg/day or placebo. RESULTS: The primary endpoint (change from SB-placebo run-in week to week 3 in weekly mean of daily average numerical rating scale [NRS] pain intensity) showed clinically relevant placebo-corrected treatment effect pain reductions at 40 mg and 150 mg/day of 0.82 (95% CI: 0.07, 1.58, p = 0.034) and 0.66 (95% CI: -0.03, 1.35; p = 0.061) NRS points, respectively, though did not meet the pre-specified value of p = 0.016 required due to multiplicity. An additional post hoc endpoint looking at the change from WO baseline to week 3 in weekly mean of daily average NRS showed the placebo-corrected treatment effect was 1.46 (95% CI: 0.26, 2.66), and 1.20 (95% CI: 0.10, 2.29) NRS points, respectively. Secondary and post hoc analyses of NRS pain data (including 30 & 50% responder rate and NNT), sleep interference, Short-form McGill pain questionnaire (especially pain intensity assessed on Visual Analogue Scale), Patient's and Clinician's Global Impression of Change showed effects consistent with the primary findings. NRD.E1 was well tolerated, with only headache reported in more than two patients and more frequently on NRD.E1 than placebo. CONCLUSIONS: The data suggest that NRD.E1 potentially represents a novel non-opioid therapeutic option for patients with PDPN, with at least similar efficacy and better tolerability than available therapies, justifying its further evaluation in larger-scale confirmatory studies. SIGNIFICANCE: NRD.E1 is a novel non-opioid therapeutic which is being developed for the treatment of PDPN. In this randomized, controlled, dose-finding, Proof of Concept study, NRD.E1 induced a clinically relevant pain reduction and it was well tolerated. Available data suggest that NRD.E1 has at least similar efficacy and better tolerability than the currently available therapies, potentially offering a promising new therapeutic option to patients with PDPN and possibly other neuropathic pain indications.

Alcohol Drinks Induce Acute Lowering in Circulating l-Arginine in Obese and Type 2 Diabetic Subjects.

Since low serum l-arginine (Arg) and high asymmetric dimethylarginine (ADMA) can predict microvascular complications in type 2 diabetes mellitus (T2DM), we tested whether Arg and ADMA are affected by diet and physical activity in overweight/obese and T2DM subjects. We tested the effects on serum Arg and ADMA of single loads of dextrose, protein, fat, or alcohol (∼300 calories each); one episode of physical exercise; and 12 weeks of standard lifestyle modification (dietary and physical activity counseling). Alcohol drink was followed by ∼30% lowering in Arg. Arg and ADMA increased after a protein load but remained stable after glucose or fat load or 30 min of treadmill walk. Following 12 weeks of lifestyle modification, ADMA declined only in subjects achieving weight loss >5%. In conclusion, alcohol is a previously unrecognized acute suppressor of serum Arg. Lifestyle modification lowers ADMA in subjects who achieve weight loss >5%. Clinical Trial Registration Number: NCT04406402.

Finerenone in Patients With Chronic Kidney Disease and Type 2 Diabetes According to Baseline HbA1c and Insulin Use: An Analysis From the FIDELIO-DKD Study.

OBJECTIVE: Finerenone significantly improved cardiorenal outcomes in patients with chronic kidney disease (CKD) and type 2 diabetes (T2D) in the Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease trial. We explored whether baseline HbA1c level and insulin treatment influenced outcomes. RESEARCH DESIGN AND METHODS: Patients with T2D, urine albumin-to-creatinine ratio (UACR) of 30-5,000 mg/g, estimated glomerular filtration rate (eGFR) of 25 to <75 mL/min/1.73 m2, and treated with optimized renin-angiotensin system blockade were randomly assigned to receive finerenone or placebo. Efficacy outcomes included kidney (kidney failure, sustained decrease ≥40% in eGFR from baseline, or renal death) and cardiovascular (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure) composite endpoints. Patients were analyzed by baseline insulin use and by baseline HbA1c <7.5% (58 mmol/mol) or ≥7.5%. RESULTS: Of 5,674 patients, 3,637 (64.1%) received insulin at baseline. Overall, 5,663 patients were included in the analysis for HbA1c; 2,794 (49.3%) had baseline HbA1c <7.5% (58 mmol/mol). Finerenone significantly reduced risk of the kidney composite outcome independent of baseline HbA1c level and insulin use (Pinteraction = 0.41 and 0.56, respectively). Cardiovascular composite outcome incidence was reduced with finerenone irrespective of baseline HbA1c level and insulin use (Pinteraction = 0.70 and 0.33, respectively). Although baseline HbA1c level did not affect kidney event risk, cardiovascular risk increased with higher HbA1c level. UACR reduction was consistent across subgroups. Adverse events were similar between groups regardless of baseline HbA1c level and insulin use; few finerenone-treated patients discontinued treatment because of hyperkalemia. CONCLUSIONS: Finerenone reduces kidney and cardiovascular outcome risk in patients with CKD and T2D, and risks appear consistent irrespective of HbA1c levels or insulin use.

Association between estimated GFR and incident hypoglycaemia during hospitalization.

BACKGROUND: Kidney function is a significant factor associated with increased incidence of hypoglycaemia, especially among patients with diabetes mellitus (DM). We here quantified the association between elevated creatinine and incident hypoglycaemia among patients admitted to internal medicine departments, with and without DM. METHODS: This is a retrospective cohort analysis study. Included were all patients discharged from internal medicine units between 2010 and 2013. Patients were excluded if creatinine levels rose or dropped more than 0.3 mg/dL during hospitalization. The CKD-EPI equation was used to calculate glomerular filtration rate (eGFR). Logistic regression analysis (backward LR method) was used to study the association between eGFR and hypoglycaemia incidence. RESULTS: Included were 39 316 patients (mean age 68.0 ± 18.0 years, 49.3% males, 25.9% with DM, eGFR 69.5 ± 24.9 mL/min/1.73 m2 ). Among study participants, 6.5% had at least one hypoglycaemic event. Logistic regression modelling showed that eGFR was inversely associated with incident hypoglycaemia (OR 0.988, 95% CI 0.986-0.990, p < .001). Results were similar for patients with and without DM. Estimated GFR was negatively correlated with admission CRP levels for patients with (r = -.143, p < .001) and without DM (r = -.166, p < .001). Estimated GFR was also positively correlated with admission serum albumin levels for both patients with (r = .304, p < .001) and without DM (r = .354, p < .001). CONCLUSION: Among non-critically-ill patients hospitalized in internal medicine departments, reduced eGFR is associated with increased risk of hypoglycaemia. Glucose monitoring for all inpatients with CKD is suggested, regardless of DM status.

[COMPARISON OF A RECOMMENDATION FOR A DESIRABLE HBA1C VALUE BY INTERNAL WARD PHYSICIANS, DIABETES PHYSICIANS AND AN APPLICATION, FOR DIABETES PATIENTS DISCHARGED FROM HOSPITALIZATION IN AN INTERNAL WARD].

INTRODUCTION: In the present study we demonstrated that there are no clinically significant differences in the recommendations of the various factors that were examined as for the determination of a desirable HbA1c goal for diabetes patients who are discharged from an internal ward. AIMS: To examine and compare the desirable HbA1c value recommended by internal ward physicians for diabetics who are discharged from hospitalization, to the target set by diabetes physicians, and compare them to the application "A1c target". BACKGROUND: The approach to diabetes treatment requires the setting of a desirable individual HbA1c balancing goal for each patient. This goal is usually set by diabetes physicians and it would be advisable that both internal and family physicians will set a desirable balancing goal as well. An online accessible application which assists in setting a desirable HbA1c goal for each patient according to his own data does exist. This application has not yet been validated. METHODS: The study was conducted in Internal ward B of the Wolfson Medical Center, and included 100 diabetes patients prior to their discharge after hospitalization for whatever reason. In the discharge letter, internal physicians recommended a desirable HbA1c value at their discretion. The patient information was forwarded to two diabetes physicians, A and B, without the HbA1c data written by the ward physicians who determined the desirable value of the HbA1c on which they had decided. Later, an HbA1c value was also determined by the application. All the data was processed statistically and compared. RESULTS: The desirable average HbA1c values by internal physicians were: 7.4%; by diabetes physician A: 7.5%; by diabetes physician B : 7.7%; the HbA1c value obtained from the application was 7.4%. There was no significant difference between the internal physicians' recommendations and those of the diabetes physician A and the application. A statistically significant difference (P> 0.0001) was found between diabetes physician B and the rest. However, from a clinical point of view - that difference has no significance. CONCLUSIONS: Based on the present study data it can be concluded that the recommendation of the internal physicians regarding the choice of a desirable HbA1c goal, is not significantly different from that of the specialists. Furthermore, it can also be concluded, that using an application may assist in choosing a desirable goal, which is also not significantly different from the goal that was recommended by both the specialists and the internal physicians. DISCUSSION: Based on the data of our study we recommend to routinely introduce written balancing goals in all the internal ward discharge letters for diabetes patients who have been hospitalized in that ward, for whatever reason.

[THE CHALLENGE OF HEALTHY AGING WITH DIABETES: THE ISRAELI NATIONAL DIABETES COUNCIL GUIDELINES FOR TREATING OLDER PEOPLE].

INTRODUCTION: The prevalence of diabetes increases with age. Diabetes is a risk factor for many complications such as cardiovascular disease, kidney failure, stroke, neuropathy, and retinopathy. Data from recent years indicate that it is also a risk factor for cognitive impairment, dementia, functional disability and frailty. Diabetes is a disease that requires complex self-care capabilities; the individuals with diabetes are required to take medications on time, examine their feet, exercise, maintain a balance diet, preform daily glucose monitoring, cope with hypoglycemia and understand how differing life situations may effect glucose levels. All of these require intact cognitive and functional abilities. Thus, treatment plans should take into consideration the person's cognitive/functional state. Indeed, in the last several years many professional organizations such as the American Diabetes Association, the International Diabetes Federation, and the American Endocrinology Society have published guidelines for treating older people with diabetes. The Israeli National Diabetes Council, headed by Prof. Itamar Raz, in collaboration with other physician unions and other national councils, have recently authorized the Israeli guidelines for treating older people with diabetes. The Israeli guidelines include categorization of older adults with diabetes in relation to their functional status in order to reach determined treatment targets. According to the Israeli guidelines and in accordance with international guidelines, the treatment targets of the elderly person with diabetes should not be determined by the chronological age of the individuals but rather by their risk for functional deterioration. Older people with diabetes are categorized into three groups according to their risk for functional deterioration. Each category has unique glucose, blood pressure and lipid targets. The guidelines offer valid and reliable tools that, in addition to personal acquaintance with the patient, can help determine the level of risk of functional decline.

Serum from type 2 diabetes patients consuming a three-meal diet resets circadian rhythms in cultured hepatocytes.

AIMS: Feeding regimens alter circadian rhythms in peripheral tissues, but the mechanism is not understood. We aimed to study whether soluble factors, rather than neuronal-based communication, directly influence circadian rhythms in the liver, in response to a nutritional treatment in type 2 diabetes (T2D) patients. METHODS: Cultured hepatocytes were treated with serum of insulin-treated T2D patients following either a three-meal diet (3Mdiet) or six-meal diet (6Mdiet) and the circadian expression of clock and metabolic genes was measured. RESULTS: Serum of the 3Mdiet group led to increased amplitudes and daily mRNA levels of the positive limb of the circadian clock (Clock, Bmal1, Rorα). In parallel, serum of the 3Mdiet group led to the downregulation of the negative limb of the circadian clock (Cry1 and Per1), compared to both baseline and 6Mdiet. In contrast, serum of the 6Mdiet group led to a more distorted expression pattern. The catabolic genes Sirt1 and Ampk were significantly upregulated only by serum of the 3Mdiet group. CONCLUSIONS: Our results show that serum of type 2 diabetes patients consuming the 3Mdiet contains soluble factors that reset circadian rhythms leading to an expression pattern similar to that of healthy people. This clock pattern contributes to improved glucose metabolism.

Role of High Energy Breakfast "Big Breakfast Diet" in Clock Gene Regulation of Postprandial Hyperglycemia and Weight Loss in Type 2 Diabetes.

Postprandial hyperglycemia (PPHG) is strongly linked with the future development of cardiovascular complications in type 2 diabetes (T2D). Hence, reducing postprandial glycemic excursions is essential in T2D treatment to slow progressive deficiency of ß-cell function and prevent cardiovascular complications. Most of the metabolic processes involved in PPHG, i.e., ß-cell secretory function, GLP-1 secretion, insulin sensitivity, muscular glucose uptake, and hepatic glucose production, are controlled by the circadian clock and display daily oscillation. Consequently, postprandial glycemia displays diurnal variation with a higher glycemic response after meals with the same carbohydrate content, consumed at dusk compared to the morning. T2D and meal timing schedule not synchronized with the circadian clock (i.e., skipping breakfast) are associated with disrupted clock gene expression and is linked to PPHG. In contrast, greater intake in the morning (i.e., high energy breakfast) than in the evening has a resetting effect on clock gene oscillations and beneficial effects on weight loss, appetite, and reduction of PPHG, independently of total energy intake. Therefore, resetting clock gene expression through a diet intervention consisting of meal timing aligned to the circadian clock, i.e., shifting most calories and carbohydrates to the early hours of the day, is a promising therapeutic approach to improve PPHG in T2D. This review will focus on recent studies, showing how a high-energy breakfast diet (Bdiet) has resetting and synchronizing actions on circadian clock genes expression, improving glucose metabolism, postprandial glycemic excursions along with weight loss in T2D.

Systemic Treatment With Glucocorticoids Is Associated With Incident Hypoglycemia and Mortality: A Historical Prospective Analysis.

PURPOSE: The purpose of this study was to examine whether the increased glycemic variability associated with systemic glucocorticoid treatment is also associated with increased incidence of hypoglycemia. METHODS: All patients discharged from internal medicine units between 2010 and 2013 were included in this retrospective analysis. Patients were assigned to 3 groups: Group 1: no steroids were prescribed;. Group 2: topical or inhaled steroids were prescribed with no systemic treatment; and Group 3: systemic steroids were prescribed, with or without topical or inhaled treatment. RESULTS: A total of 45,272 patients were included in the study. Patients in Group 3 had significantly higher rates of hypoglycemia (10.9%) compared to patients in Group 2 (7.4%), and patients in Group 1 (7.3%). Patients with diabetes mellitus had higher rates of hypoglycemia compared to patients without diabetes mellitus (14.3% vs 4.9%) but exhibited similar trends in response to steroid treatment. Multivariate analysis showed that systemic steroids were associated with increased risk for hypoglycemia (odds ratio [OR] 1.513, 95% confidence interval [CI] 1.311-1.746, P <0.001). Hypoglycemia associated with systemic steroid treatment was also associated with increased risk of death (hazard ratio [HR] 2.328, 95% CI 1.931-2.807, P <0.001). Patients who were treated with systemic steroids but did not have hypoglycemia did not have higher mortality rates (HR 1.068, 95% CI 0.972-1.175, P = 0.171). CONCLUSION: Treatment with systemic steroids is associated with increased hypoglycemia incidence during hospitalization. Patients treated with steroids that had incident hypoglycemia had a higher 1-year mortality risk compared to patients without hypoglycemia treated with steroids.

Effect of Once-Weekly Exenatide in Patients With Type 2 Diabetes Mellitus With and Without Heart Failure and Heart Failure-Related Outcomes: Insights From the EXSCEL Trial.

BACKGROUND: Once-weekly exenatide (EQW) had a neutral effect on hospitalization for heart failure (HHF) in the EXSCEL study (Exenatide Study of Cardiovascular Event Lowering), with no differential treatment effect on major adverse cardiac events by baseline heart failure (HF) status. EQW's effects on secondary end points based on HHF status have not been reported. The objective was to explore the effects of EQW on secondary end points in patients with and without baseline HF and test the effects of EQW on recurrent HHF events. METHODS: The prespecified analysis of the randomized controlled EXSCEL trial, which enrolled patients with type 2 diabetes mellitus with and without additional cardiovascular disease, analyzed EQW effects on all-cause death, each major adverse cardiac event component, first HHF, and repeat HHF, by baseline HF status (regardless of ejection fraction). A subgroup analysis of the population stratified by preserved or reduced baseline ejection fraction was performed. RESULTS: Of 14 752 EXSCEL participants, 2389 (16.2%) had HF at baseline. Compared with those without HF at baseline, patients with preexisting HF were older, and more likely to be male and white, with a higher burden of other cardiovascular diseases. Overall, those assigned to EQW had a lower incidence of all-cause death (hazard ratio [HR], 0.86 [95% CI, 0.77-0.97]) and the composite outcome of all-cause death or HHF (HR, 0.89 [95% CI, 0.80-0.99]). When stratified by presence or absence of baseline HF, there was no observed reduction in all-cause death with EQW with baseline HF (HR, 1.05 [95% CI, 0.85-1.29]), while the risk of mortality was reduced with EQW in the no-HF group (HR, 0.79 [95% CI, 0.68-0.92]) with an interaction P value of 0.031. The reduction in all-cause death or HHF seen with EQW in patients without baseline HF (HR, 0.81 [95% CI, 0.71-0.93]) was not seen in patients with baseline HF (HR, 1.07 [95% CI, 0.89-1.29]; interaction P=0.015). First, plus recurrent, HHF was reduced in the exenatide group versus placebo (HR, 0.82 [95% CI, 0.68-0.99]; P=0.038). CONCLUSIONS: In EXSCEL, the use of EQW in patients with or without HF was well tolerated, but benefits of EQW on reduction in all-cause death and first hospitalization for HF were attenuated in patients with baseline HF. CLINICAL TRIAL REGISTRATION: https://www.clinicaltrials.gov. Unique identifier: NCT01144338.

Reduction in Glycated Hemoglobin and Daily Insulin Dose Alongside Circadian Clock Upregulation in Patients With Type 2 Diabetes Consuming a Three-Meal Diet: A Randomized Clinical Trial.

OBJECTIVE: In type 2 diabetes, insulin resistance and progressive ß-cell failure require treatment with high insulin doses, leading to weight gain. Our aim was to study whether a three-meal diet (3Mdiet) with a carbohydrate-rich breakfast may upregulate clock gene expression and, as a result, allow dose reduction of insulin, leading to weight loss and better glycemic control compared with an isocaloric six-meal diet (6Mdiet). RESEARCH DESIGN AND METHODS: Twenty-eight volunteers with diabetes (BMI 32.4 ± 5.2 kg/m2 and HbA1c 8.1 ± 1.1% [64.5 ± 11.9 mmol/mol]) were randomly assigned to 3Mdiet or 6Mdiet. Body weight, glycemic control, continuous glucose monitoring (CGM), appetite, and clock gene expression were assessed at baseline, after 2 weeks, and after 12 weeks. RESULTS: 3Mdiet, but not 6Mdiet, led to a significant weight loss (-5.4 ± 0.9 kg) (P < 0.01) and decreased HbA1c (-12 mmol/mol [-1.2%]) (P < 0.0001) after 12 weeks. Fasting glucose and daily and nocturnal glucose levels were significantly lower on the 3Mdiet. CGM showed a significant decrease in the time spent in hyperglycemia only on the 3Mdiet. Total daily insulin dose was significantly reduced by 26 ± 7 units only on the 3Mdiet. There was a significant decrease in the hunger and cravings only in the 3Mdiet group. Clock genes exhibited oscillation, increased expression, and higher amplitude on the 3Mdiet compared with the 6Mdiet. CONCLUSIONS: A 3Mdiet, in contrast to an isocaloric 6Mdiet, leads to weight loss and significant reduction in HbA1c, appetite, and overall glycemia, with a decrease in daily insulin. Upregulation of clock genes seen in this diet intervention could contribute to the improved glucose metabolism.

High-Intensity Statins Are Associated With Increased Incidence of Hypoglycemia During Hospitalization of Individuals Not Critically Ill.

BACKGROUND: Serum cholesterol is inversely associated with incident hypoglycemia among patients admitted to internal medicine wards. We examined the association between statin use and incidence of hypoglycemia among patients who were not critically ill. METHODS: In this retrospective study, we included all patients discharged between January 1, 2010, to December 31, 2013 from internal medicine units at the Wolfson Medical Center. Excluded were patients with hepatocellular or cholestatic liver disease upon admission. Patients were allocated to 4 groups, according to diabetes mellitus status (yes or no) and serum albumin <3.5 g/dL (yes or no) on admission. Regression analysis was used to examine the association of incident hypoglycemia during hospitalization and statin treatment (yes or no), and later, statin intensity. RESULTS: Included in this analysis were 31,094 patients (mean age 68.9±17.5 years, 48.4% males, 21.7% with diabetes mellitus). Logistic regression models showed that among patients with low admission serum albumin, administration of high-intensity statins was associated with increased incidence of hypoglycemic events compared to patients not treated with statins (odds ratio [OR] 1.303, 95% confidence interval [CI] 1.016-1.671, P = 0.037), whereas treatment with low-intensity statins was associated with less hypoglycemic events (odds ratio 0.590, 95% confidence interval 0.396-0.879, P = 0.010). Among patients with normal serum albumin, no association was found between incident hypoglycemia and statin intensity. These findings were significant regardless of diabetes mellitus status. CONCLUSION: Statin treatment in general is associated with reduced incidence of hypoglycemia. However, among patients with low serum albumin upon admission, use of high-intensity statins is associated with an increased risk of hypoglycemic events regardless of diabetes mellitus status.

Effect of Flash Glucose Monitoring Technology on Glycemic Control and Treatment Satisfaction in Patients With Type 2 Diabetes.

OBJECTIVE: To assess treatment satisfaction and the effectiveness of a flash glucose monitoring (FGM) system in patients with type 2 diabetes using insulin. RESEARCH DESIGN AND METHODS: A total of 101 patients with type 2 diabetes on multiple daily insulin injections (MDI) for at least 1 year were assigned randomly to the FGM intervention (n = 53) or the standard care (control) group (n = 48) and followed for 10 weeks. Both groups were instructed to adjust their insulin doses in face-to-face and telephone visits. Satisfaction with treatment, quality of life, comfort using FGM, HbA1c, and frequency of hypoglycemic events were evaluated. RESULTS: The intervention group found treatment significantly more flexible (P = 0.019) and would recommend it to their counterparts (P = 0.023). Satisfaction using the FGM system was high. The changes in HbA1c were -0.82% (9 mmol/mol) vs. -0.33% (3.6 mmol/mol) in the intervention and control group, respectively (P = 0.005); in nonprespecified post hoc analysis, 68.6% of the patients in the intervention group had their HbA1c reduced by ≥0.5% (5.5 mmol/mol) compared with 30.2% in the control group (P < 0.001), and 39.2% had their HbA1c reduced by ≥1.0% (10.9 mmol/mol) vs. 18.6% in the control group (P = 0.0023) without an increased frequency of hypoglycemia. CONCLUSIONS: FGM tends to improve treatment satisfaction and may lead to amelioration of glycemic control in patients with type 2 diabetes on MDI without increasing the frequency of hypoglycemia.

Documented hypoglycemia is associated with poor short and long term prognosis among patients admitted to general internal medicine departments.

AIM: To study the association of documented hypoglycemia with length of stay, 30-day mortality, and 1-year mortality, among patients with and without diabetes admitted to internal medicine units. METHODS: The electronic medical records of all patients hospitalized in internal medicine departments at E. Wolfson Medical Center, Holon, Israel, between 1/1/2010 and 31/12/2013, were reviewed. Data extracted included all glucose measurements (performed using an institutional blood glucose monitoring system). Patients were considered hypoglycemic if at least one hypoglycemic event was recorded. Regression analysis was used to assess the association between documented hypoglycemia and length of stay, 30-day and one-year mortality. Age, sex, reason for admission, and the Charlson comorbidity index were entered as covariates, and the most conservative model was developed. RESULTS: The study population included 45,272 patients (mean age 68.9 ±â€¯17.8 years, 49.4% males, 21.0% had diabetes mellitus). The rate of hypoglycemia in the total study population was 7.5% (16.8% among DM patients, 6.0% among patients without diabetes, p < 0.001). Patients with documented hypoglycemia had a longer length of hospital stay (9.3 ±â€¯18.7 vs. 3.1 ±â€¯6.4 days, p < 0.001), as well as higher risk for both 30-day (23.7% vs. 7.0%, p < 0.001) and 1-year mortality (41.6% vs. 15.3%, p < 0.001). Cox regression analysis showed that hypoglycemia significantly increased risk death at one year (HR 2.436, 95% CI 2.298-2.582, p < 0.001) independent of age, sex, the Charlson comorbidity index, DM status and reason for admission. CONCLUSION: Documented hypoglycemia is associated with prolonged length of hospital stay and increased risk for both 30-day and 1-year mortality, regardless of diabetes mellitus status.

Improved outcome of patients with diabetes mellitus with good glycemic control in the cardiac intensive care unit: a retrospective study.

BACKGROUND: Diabetes mellitus (DM) is a prevalent metabolic disease characterized by chronic hyperglycemia. A primary burden of DM is related to its long-term complications, which have been shown to impact the course of hospitalization and to influence patients' outcome. AIM: To assess the role of in-hospital glucose control on length of stay, 30-days and 1-year mortality. METHODS: This is a retrospective study that included patients admitted to the cardiac intensive care unit (CICU) of the Edith Wolfson Medical Centre between 01 January, 2010 and 31 December 2013. Blood glucose was measured by glucometer and fed into an interactive database. Glucose status was referred to as controlled when more than 50% of a given patients glucose values were between 71 and 200 mg/dL. Chisquared tests were used to assess the distribution of categorical variables, while the ttest was applied for continuous variables. A multivariate logistic regression model was used to analyze the association between glucose control and mortality. Cox regression was conducted to assess survival and 1-year mortality. RESULTS: 2466 patients were admitted to the CICU over the study period, of which 370 had concomitant diabetes mellitus. Controlled glucose status was associated with shorter length of hospital stay (1.6 ± 1.7 versus 2.6 ± 3.0, p < 0.001), reduced 30-day mortality (0.7% versus 4.6%, p < 0.001), and improved 1-year mortality (2.2% versus 7.5%, p < 0.001). Moreover, attainment of glucose control was independently associated with a significant decrease in 1-year mortality (OR = 0.371, 95% CI 0.140-0.988, p = 0.047). CONCLUSION: In-hospital control of glucose parameters is associated with shorter length of hospital stay, and lowered 30-day and 1-year mortality. An effort to maintain glucose levels within reference ranges is warranted in critically ill patients to reduce mortality.

Hypoglycemia- simplifying the ways to predict an old problem in the general ward.

OBJECTIVE: To examine the association between hypoglycemic events and inpatient and outpatient mortality rates, and to characterize the profile of patients with diabetes who develop hypoglycemia during hospitalization in order to identify risk factors and potentially avoid it. RESEARCH DESIGN AND METHODS: This retrospective cohort study analyzed data of 3410 patients with diabetes hospitalized during 2012. The associations among biochemical measures, severity of hypoglycemia, inpatient length of stay, and mortality during hospitalization, one month and within one year after discharge were evaluated. RESULTS: Hypoglycemia was observed in 18.5% (633/3410) of patients with diabetes, 83% (529/633) with mild/moderate hypoglycemic values. Adjusted for age and sex, the 30-day mortality rate after discharge was higher in the group with mild/moderate hypoglycemia (HR = 1.749, CI 1.288-2.374, p < 0.001) and in the group with severe hypoglycemia (HR = 3.390, CI 2.332-6.100, p < 0.001). The mortality rate at the one-year follow-up was higher in the group with mild/moderate hypoglycemia (HR = 1.749, CI 1.288-2.374, p < 0.001) and in the group with severe hypoglycemia (HR = 3.390, CI 2.332-6.100, p < 0.001). In multivariate analysis, hemoglobin and albumin below normal values, and creatinine values above the upper limit were strongly associated with hypoglycemia (OR 1.35, 95%CI 1.1-1.6, p < 0.03; OR 1.6, 95%CI 1.33-1.89, p < 0.001; OR 1.3, 95%CI 1.08-1.55, p < 0.04, respectively). CONCLUSIONS: Hospitalized patients with diabetes and low hemoglobin, low albumin or high creatinine levels are at increased risk of developing significant hypoglycemia. Identifying accurate high-risk factors in order to intervene early and efficiently can prevent life-threatening complications.