Diabetic Patients Receiving Insulin Therapy Research Articles

Transient increase in glucose variability during Ramadan fasting in patients with insulin-treated type 2 diabetes: A preliminary study

AimWe aimed to examine the effect of Ramadan fasting on interstitial glucose control and variability before, during, and after Ramadan in type 2 diabetes patients receiving insulin therapy. MethodsParticipants received a flash glucose monitoring (FGM) system one week before Ramadan that was removed on the sixth or seventh day (pre- and early Ramadan periods) of Ramadan and a second FGM system one week before the end of Ramadan that was removed one week after the end of Ramadan (late and post-Ramadan periods). Fasting blood samples were collected during the pre-, early, and late Ramadan study visits and tested for HbA1c, serum creatinine, and plasma glucose levels. ResultsThirty-four patients were prospectively included. The standard deviation and coefficient of variation of glucose concentrations were higher in the early Ramadan period than in the pre-Ramadan period, but did not differ in the late or post-Ramadan periods. Changes in the early Ramadan period were restricted to males and patients aged <55 years. No significant changes were observed in the average glucose level, glucose management indicator, time in range, time in hyperglycemia, or time in hypoglycemia at any time point. ConclusionsRamadan fasting in patients with insulin-treated type 2 diabetes is associated with an initial increase in glucose variability that quickly returned to pre-Ramadan levels. Ramadan fasting was not associated with any significant changes in glycemic control measures.

Prediction of atrial fibrillation and sudden cardiac death in type 2 diabetic patients on insulin: a territory-wide observational cohort study

Abstract Funding Acknowledgements Type of funding sources: None. Introduction With the global shift towards a more personalized approach in the management of diabetes, there is an increasing interest in exploring the application of new parameters, such as HbA1c and lipid variability, to better monitor disease progression and evaluate the prognosis. Given that metabolic abnormalities may exacerbate the risk of adverse outcomes in patients with type 2 diabetes mellitus, patients who are partially or fully dependent on insulin are more likely to have severe disease and may be at higher risks of arrhythmias. Purpose The aim of the present study aims was to assess the predictive value of HbA1c and lipid variability towards ventricular tachycardia (VT), ventricular fibrillation (VF), or SCD, as well as incident AF in type 2 diabetic patients receiving insulin therapy. Methods The territory-wide retrospective observational study consists of type 2 diabetic patients prescribed with insulin, who attended publicly funded clinics and hospitals in Hong Kong between January 1st, 2009 to December 31st, 2009. Variability in total cholesterol, low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), triglyceride, and HbA1c were assessed through their standard deviation (SD) and coefficient of variation (CV) for patients with at least three measurements of the respective indices. Univariate and multivariate Cox regression analysis was used to predict for the primary outcomes- incident SCD and AF. Results A total of 23329 patients (mean ± SD age: 64 ± 14 years old; 51% male; mean HbA1c 8.6 ± 1.3%) were included. In total, 2512 and 1846 patients experienced incident SCD and AF respectively over the course of follow-up. On multivariate analysis, higher HbA1c variability (SD: hazard ratio [HR]: 1.45, 95% confidence interval [CI] 1.21-1.75; p &amp;lt; 0.0001) and triglyceride variability (SD: HR: 1.36, 95%CI: 1.24-1.49; p &amp;lt; 0.0001) were associated with increased of SCD risk. By contrast, only the increase in LDL-C variability was predictive of AF (SD: HR 2.95, 95%CI 1.37-6.39; p= 0.006). Conclusions Higher HbA1c variability and lipid variability were associated with increased of SCD risk while only higher LDL-C variability was predictive of incident AF. Therefore, poor glucose control and variability in lipid parameters in diabetic patients are associated with SCD and incident AF. These observations suggest the need to re-evaluate the extent of glycemic control required for outcome optimization.

59-LB: Prevalence and Risk Factors of Lipohypertrophy and Lipoatrophy in Diabetes Patients Receiving Insulin Therapy

Objectives: Insulin therapy is associated with skin-related complications, such as lipoatrophy, lipohypertrophy (LH), edema, and allergy. Lipohypertrophy (LH) is the most common cutaneous complication of injectable insulin therapy in the treatment of diabetes. Our aim in this study was to evaluate skin-related complications in diabetic patients receiving insulin therapy. Methods: In this study, diabetic patients who were treated with insulin therapy in Endocrinology Department between 2015 and 2018 were evaluated. Observation and palpation technique was used in the evaluation of lipohypertrophy in diabetic subjects. The degree of lipohypertrophy was classified as follows: grade 0 = no change; grade 1 = visible hypertrophy of fat tissue but with normal consistency on palpation; grade 2 = intensive fat tissue thickening but with firm consistency; and grade 3 = lipoatrophy Results: A total of 204 diabetic participants (52, 5 % female) were evaluated. The number of patients using insulin for more than 10 years was 81 (39,7%). The 4-mm needle was used more commonly in the study (54, 4 %). The recommended injection sites are the abdomen, thigh, arm and buttocks. Overall, 55, 9 % of patients were injecting insulin in the area of abdomen and 40, 2 % were injecting insulin four times per day. The ratio of the patients who do not change needle tip for each injection was 43,6%. In addition, lipohypertrophy was seen in 61, 8 % of the 204 diabetics in the study and most patients were revealed to have grade 1 (35,3%). Lipoatrophy was seen in 5.6% of the patients. Of the cases diagnosed as lipohypertrophy, 56, 3 % were women and 43,7% were men. Females were significantly more likely to have LH than males were (P = 0.042). Conclusions: Increased prevelance of lipohypertrophy is an important complication of insulin therapy and clinicians must be aware of this complication. Disclosure B. Aydin Buyruk: None. N. Kebapci: None. G. Yorulmaz: None. E. Alaguney: None. A. Akalin: None. B. Efe: None.

Erratum to: Efficacy of Additional Canagliflozin Administration to Type 2 Diabetes Patients Receiving Insulin Therapy: Examination of Diurnal Glycemic Patterns Using Continuous Glucose Monitoring (CGM).

Unfortunately, the original publication of this paper contained errors in the presentation of Fig.2.

Efficacy of Additional Canagliflozin Administration to Type 2 Diabetes Patients Receiving Insulin Therapy: Examination of Diurnal Glycemic Patterns Using Continuous Glucose Monitoring (CGM).

IntroductionThe efficacy of administering a sodium–glucose cotransporter 2 inhibitor during insulin therapy has not been established. In this study, we examined its effects based on diurnal glycemic patterns using continuous glucose monitoring (CGM).MethodsThe subjects were 15 patients who had received insulin therapy for 1 year or more. A CGM device was attached to all subjects for 1 week. The administration of canagliflozin at 100 mg was started 4 days after attachment. The mean glucose concentrations, standard deviation (SD), mean amplitude of glycemic excursions (MAGE), mean of daily difference of blood glucose (MODD), and area under the curve (AUC) (≥180, <70 mg h/dL) after the start of administration were compared with the pretreatment values. In addition, we compared changes in the number of insulin units between basal and bolus insulin. Furthermore, we investigated the influence of canagliflozin on oxidative stress markers and cytokines using 8-hydroxy-2′-deoxyguanosine (8-OHdG), tumor necrosis factor-α (TNF-α), and adiponectin as parameters.ResultsThe mean glucose concentrations decreased from 161.1 to 139.1 mg/dL (P < 0.01). The SD decreased from 36.5 to 29.6 mg/dL (P = 0.05). The MAGE decreased from 89.2 to 77.4 mg/dL (P < 0.01), and the MODD decreased from 34.3 to 25.5 mg/dL (P < 0.05). All parameters showed significant improvements in diurnal changes. AUC of ≥180, i.e., the total area of blood glucose levels at or above 180 on the blood glucose curve of CGM, decreased from 339.1 to 113.6 mg/dL (P < 0.05). AUC of <70, i.e., the total area of blood glucose levels below 70 on the blood glucose curve of CGM, slightly decreased from 1.6 to 0.3 mg/dL (P = 0.08). The total number of basal insulin units decreased from 128 to 76, and that of bolus insulin decreased from 266 to 154; the dose of insulin could be markedly decreased. In addition, the mean 8-OHdG level decreased from 11.4 to 10.8 ng/mg Cre (P < 0.05), and the mean TNF-α level decreased from 2.31 to 1.79 pg/mL (P = 0.10). The mean adiponectin level increased from 5.01 to 5.53 μg/mL (P < 0.05).ConclusionCanagliflozin improved blood glucose changes in type 2 diabetes using insulin. In addition, the results suggest its antioxidant actions.Trial RegistrationUniversity Hospital Medical Information Network (UMIN no. 000019429).

Association between factors associated with colorectal cancer and rectal aberrant crypt foci in humans.

Aberrant crypt foci (ACF) are regarded as potential biomarkers for colorectal cancer (CRC), and have been used as such in recent early-phase chemoprevention trials. However, the associations between the presence of ACF and other factors associated with the development of CRC, such as lifestyle factors, medication use and comorbid medical conditions, remain unknown. Thus, the present retrospective, large, cross-sectional study was conducted to evaluate the potential usefulness of ACF as a surrogate biomarker of CRC. Total colonoscopy was performed and the number of rectal ACF was counted in a total of 902 subjects. A retrospective review of the medical records of the study subjects was performed, and the factors associated with the increased prevalence of ACF was investigated using univariate and multivariate logistic regression analyses. The analysis results identified older age [odds ratio (OR), 9.24; 95% confidence interval (CI), 4.80-17.8; P<0.01], smoking habit (OR, 1.78; 95% CI, 1.20-2.63; P<0.01) and use of insulin (OR, 9.97; 95% CI, 1.28-77.5; P=0.03) as significant independent risk factors associated with the increased prevalence of ACF, regardless of the presence/absence of colon tumors. In addition, it was revealed that the prevalence and number of ACF, and the Ki-67 labeling indices of the colonic epithelial cells were significantly higher in diabetic patients receiving insulin therapy than in those not receiving insulin therapy (P<0.01, P=0.03 and P=0.01, respectively). In conclusion, the potential usefulness of ACF as a surrogate biomarker of CRC was confirmed, although useful data could not be obtained on candidate chemopreventive agents. These results indicated that insulin can enhance colonic epithelial proliferative activity and induce the formation of ACF, thereby possibly triggering CRC development.

One-minute mental status examination for category fluency is more useful than mini-mental state examination to evaluate the reliability of insulin self-injection in elderly diabetic patients.

We investigated the factors associated with the reliability of insulin self-injection in elderly diabetic patients receiving insulin therapy. We enrolled diabetic patients aged ≥65years and receiving insulin therapy, and assessed their cognitive function by the mini-mental state examination and 1-min mental status examination for category fluency. We also observed their technique of insulin self-injection, and evaluated whether or not patients were able to inject insulin by themselves according to nine defined details in terms of insulin self-injection. The predictive factors for the reliability of insulin self-injection were determined by univariate and multivariate logistic regression analysis. There were 278 participants (135 males, 143 females) enrolled in the present study. According to multivariate logistic regression analysis, only the 1-min mental status examination score was found to be a significant independent predictor of the reliability of insulin self-injection (odds ratio 0.75; 95% confidence interval 0.62-0.90; P=0.002). The 1-min mental status examination for category fluency can be considered more useful than mini-mental state examination to evaluate the reliability of insulin self-injection in elderly diabetic patients receiving insulin therapy.

Effects of Add-On Treatment with Sitagliptin on Narrowing the Range of Glucose Fluctuations in Japanese Type 2 Diabetes Patients Receiving Insulin Therapy

In an earlier continuous glucose monitoring (CGM)-based study, we reported that sitagliptin not only reduced 24-h mean glucose levels but also suppressed postprandial glucose increases, thus reducing the range of glycemic fluctuations in type 2 diabetes patients. In this study, we investigated whether sitagliptin might provide similar benefits in type 2 diabetes patients receiving insulin therapy by using CGM. The study included a total of 13 type 2 diabetes patients in whom stable glycemic control had been achieved after admission for glycemic control. Insulin regimens used included long-acting insulin preparations once daily in four patients and biphasic insulin preparations twice daily in nine, with the daily insulin dose being 19.0±12.7 U. During the CGM-based study, the patients were given insulin therapy alone on Days 1 and 2 and were given sitagliptin 50 mg/day as add-on treatment on Days 3-6, with their daily insulin doses maintained. The add-on treatment with sitagliptin led to significant decreases in 24-h mean glucose levels and SDs of 288 glucose levels measured by CGM for 24 h, as well as in the indices for magnitude of glucose variability and proportion of time in hyperglycemia, compared with insulin therapy alone (P<0.01), whereas there was no significant change seen in regard to the proportion of time in hypoglycemia with or without add-on treatment with sitagliptin. This CGM-based study clearly demonstrated that insulin therapy alone, whether with long-acting or biphasic insulin preparations, does not provide adequate glycemic control in type 2 diabetes patients. In contrast, add-on sitagliptin was shown to narrow the range of 24-h glucose fluctuations in these patients, suggesting that add-on treatment with sitagliptin is effective for postprandial glucose control in type 2 diabetes patients receiving insulin therapy.

The Effectiveness of Diamel in the Treatment of Type 2 Diabetic Patients Receiving Insulin Therapy: A Randomized, Controlled Clinical Trial

Aims/Introduction: Effectiveness of Diamel? on the biochemical variables: fasting blood glucose, postprandial glucose, cholesterol, triglycerides, and glycosylated haemoglobin [HbA1c] in type-2 diabetic patients receiving insulin terapy. Diamel is a natural product composed of trace elements: amino acids, vitamins, cranberry extract, and lettuce extract that have been activated by means of a magnetization process. Materials and methods: Randomized, doubleblind, comparator-controlled clinical trial. A central randomization centre used computer generated tables to allocate treatments. 116 patients suffering from type-2 diabetes mellitus treated with insulin at the Diabetes Care Centre in Pinar del Rio (Cuba), were recruited and randomly. The subjects were separated into two groups: Group A (n = 59), who were administered Diamel and Group B (n = 57) using placebo. The clinical and biochemical variables were assessed for 24 weeks. Results: Two subjects were excluded from the Diamel treatment group during the clinical trial. From the statistical point of view, a significant drop in the levels of the baseline glucose, postprandial glucose, glycated haemoglobin, and triglycerides was observed in the group taking Diamel (Group A). There was observed an increase in insulin requirements and in waist circumference in the subjects of Group B There was not reported any severe or serious adverse reactions during this clinical trial. Conclusion: Diamel (nutritional supplement) together with the administration of insulin in type-2 diabetic patients is useful to optimize the biochemical variables (baseline and postprandial glucose, Hb A1C, plus triglycerides), as well as to prevent the increase of insulin requirements at medium-term.

One-Year Efficacy and Safety of the Telehealth System in Poorly Controlled Type 2 Diabetic Patients Receiving Insulin Therapy

To evaluate the functionality of the telehealth system in poorly controlled type 2 diabetic (T2D) patients receiving insulin injections. Sixty-four patients with glycosylated hemoglobin (HbA(1c)) values > 7% for more than 1 year were included. All patients underwent an intensive diabetes management program, including titration of insulin, blood glucose-self monitoring, and nutritional review, and 32 participated in the telehealth system. The major outcome was to evaluate the change of the HbA(1c) and body weight, the incidence of hospitalization, and hypoglycemic events. After 1-year management, patients receiving telehealth care had significantly improved HbA(1c) levels (9.5% ± 1.8% to 8.1% ± 1.2%; p < 0.01) without significant body weight gain. In contrast, the control group patients had no significant improvement in HbA(1c) levels but showed significant increase in body weight (66.8 ± 9.8 to 67.3 ± 10.0 kg; p < 0.01). No patient in the telehealth group was hospitalized during the follow-up period, but six patients in the control group were. Intergroup differences in hypoglycemic events were absent. The intensive diabetes management program with the telehealth system is a useful education method to improve blood sugar control and prevent hospitalization in poorly controlled T2D patients receiving insulin injections.

Improvement in health‐related quality of life, independent of fasting glucose concentration, via insulin pen device in diabetic patients

Using an insulin pen may improve the quality of life (QOL) for diabetic individuals. However, glycemic control and its relationship to better QOL are controversial. The aim of this study was to determine the relationship between health-related QOL and glycemic control in diabetic patients using insulin pen. All of the participants were diabetic patients receiving insulin therapy by syringe injection for longer than 1 month. One group of enrolled subjects changed over to use of insulin pen for 12 weeks, while the other group (age-matched control subjects) continued to use syringe for insulin-injection during the same period. Fasting plasma glucose, HbA1c and a 36-Item Short-Form Health Survey (SF-36) were assessed in both groups before and after the 12-week study. A total of 32 subjects in the insulin pen group and 33 subjects in the syringe group completed the assessment. In comparison with baseline, fasting glucose significantly decreased in the insulin pen group (-57 +/- 14 mg dL(-1), P < 0.001), and the reduction was significantly greater than that in the syringe group (P = 0.003). The summary scale of physical components but not mental components in the SF-36 was significantly higher in the insulin pen group than in the syringe group (P = 0.037). This improvement was independent of the change in fasting glucose. Using insulin pen for insulin-injection improved glycemic control and health-related QOL in diabetic patients. The better functional health status as a result of physical improvement was independent of the glycemic control.

Significance of diabetes mellitus in patients with acute myocardial infraction receiving thrombolytic theraphy

Objectives. The purpose of this study was to evaluate the risks and benefits associated with thrombolytic theraphy in patients with diabetes presenting with acute myocardial infarction.Background. Diabetes mellitus is associated with adverse risk factors and a hypercoagulable state that may adversely affect the outcome of thrombolytic therapy.Methods. Data were analyzed from 8,055 of the 8,239 patients with acute myocardial infarction who received thrombolytic therapy in the International Tissue plasminogen Activator/Streptokinase Mortality trial (diabetes history was missing for 184 patients).Results. There were 883 patients with and 8,272 patients without diabetes. Among the diabetic patients, 160 were receiving insulin therapy. Baseline risk factors were significantly worse in diabetic patients, who were older and had a higher rate of previous infarction and antecedent angina and a higher Killip grade at admission. Bleeding and hemorrhagic and ischemic stroke rates were similar among diabetic and nondiabetic patients. Hospital and 6-month mortality rates were highest among diabetic patients receiving insulin therapy (16.9% and 23.1%, respectively), followed by diabetic patients not receiving insulin therapy (11.8% and 17.8%), and lowest in nondiabetic patients (7.5% and 10.7%, p < 0.0001). Whereas diabetes of 5 years' duration was associated with a mortality rate similar to that of nondiabetic patients, a >5-year duration was associated with a relative mortality risk of 1.38 (95% cofidence interval [CI] 0.88 to 2.15) and a > 10-year duration with a relative mortality risk of 1.99 (95% CI 1.40 to 2.81). The independent relative risk for incremental mortality from discharge to 6 months was 1.74 (95% CI 1.21 to 2.50). Mortality rate among diabetic was patients lowest in patients who received both streptokinase and heparin (9.8% vs. 16.1% in patients who received streptokinase but no heparin, p < 0.05).Conclusions. The relative mortality of diabetis versus nondiabetic patients was similar to that observed in previous studies of patients with myocardial infarction not receiving thrombolytic therapy, indicating that mortality in diabetic patients receiving thrombolytic therapy is reduced to the same extent as in nondiabetic patients. In addition, risk of bleeding and stroke was not increased, indicating that diabetic patients can safely receive thrombolytic therapy for the same indications as nondiabetic patients.

The Effect of Acarbose on Blood Glucose Profiles of Type 2 Diabetic Patients Receiving Insulin Therapy

Nine patients with Type 2 diabetes receiving insulin therapy were treated with acarbose 100 mg thrice daily for 1 week to investigate the effect of acarbose on blood glucose control. Daily blood glucose profiles contained fewer excursions during acarbose administration and low levels were maintained. The M-value, an indicator of blood glucose fluctuation, decreased significantly from a run-in period value of 37.6 +/- 8.7 (SEM) to 16.7 +/- 4.0 during the acarbose period (p < 0.05) and rose again to 28.9 +/- 6.7 (p > or = 0.05) in the follow-up period. The 24-h urinary glucose excretion similarly decreased during acarbose administration. As expected, no decrease in HbA1C was observed due to the short treatment period. The 24-h urinary C-peptide excretions and serum lipids were not influenced by acarbose therapy. Frequent episodes of clinical hypoglycaemia were experienced while on acarbose therapy, indicating a decrease in insulin requirements. Adverse events such as flatulence and abdominal distention were observed in six out of nine cases. Symptoms were generally mild and well tolerated, only one patient dropped out because of diarrhoea and abdominal pain. We conclude that acarbose could usefully be administered to Type 2 diabetic patients treated with insulin to improve blood glucose control and reduce insulin requirement if the appropriate selection criteria were met.

Protein A-sepharose used to measure free insulin in plasma

Diabetic patients receiving insulin therapy generally develop anti-insulin antibodies that must be eliminated, usually by extraction with polyethylene glycol (PEG), before determining the concentration of free (active) insulin in plasma. We describe a new method for removing such antibodies, with the use of Protein A coupled to Sepharose microspheres. The results correlate well with those by the PEG method, although values are systematically higher or lower for given samples, according to the initial titer of the antibody measured in terms of binding capacity. Further studies are required to clarify this observation.

Determination of glycohemoglobins by a rapid batch separation.

Glycohemoglobin, a minor component of hemoglobin, reaches elevated levels in uncontrolled diabetes mellitus. Because of the long-term effects of glycosylated hemoglobin, its determination in blood can prove to be an effective clinical tool in the management of the diabetic patient. This paper will describe a new batch ion exchange method for the determination of glycohemoglobins that precludes the necessity for specialized equipment. Eighty-four ambulatory subjects having no indication of diabetes mellitus and 32 diabetic patients receiving insulin therapy were assayed for blood glycohemoglobin content by the rapid batch method. The effectiveness and reliability of this method were tested by correlating parallel assays of the method with commercially available column methods. The diagnostic usefulness of the rapid batch method was determined by its predictive value. Results from this study support the validity of the rapid batch method.