Risk Of Hypoglycemia In Type Research Articles

Relationship between hemoglobin glycation index and risk of hypoglycemia in type 2 diabetes with time-in-range in target

BACKGROUND In patients with type 2 diabetes mellitus (T2DM), the risk of hypoglycemia also occurs in at a time-in-range (TIR) of > 70%. The hemoglobin glycation index (HGI) is considered the best single factor for predicting hypoglycemia, and offers new perspectives for the individualized treatment of patients with well-controlled blood glucose levels that are easily ignored in clinical settings. AIM To investigate the relationship between HGI and hypoglycemia and the implications of HGI on hypoglycemia in T2DM with TIR > 70%. METHODS All participants underwent a 7-days continuous glucose monitoring (CGM) using a retrospective CGM system. We obtained glycemic variability indices using the CGM system. We defined HGI as laboratory hemoglobin A1c minus the glucose management indicator. Patients were categorized into low HGI (HGI < 0.5) and high HGI groups (HGI ≥ 0.5) according to HGI median (0.5). Logistic regression and receiver operating characteristic curve analyses were used to determine the risk factors for hypoglycemia. RESULTS We included 129 subjects with T2DM (54.84 ± 12.56 years, 46% male) in the study. Median TIR score was 90%. The high HGI group exhibited lower TIR and greater time below range with higher hemoglobin A1c than the low HGI group; this suggests more glycemic excursions and an increased incidence of hypoglycemia in the high HGI group. Multivariate analyses revealed that mean blood glucose, standard deviation of blood glucose and HGI were independent risk factors for hypoglycemia. Receiver operating characteristic curve analysis indicated that the HGI was the best predictor of hypoglycemia. In addition, the optimal cut-off points for HGI, mean blood glucose, and standard deviation of blood glucose in predicting hypoglycemia were 0.5%, 7.2 mmol/L and 1.4 mmol/L respectively. CONCLUSION High HGI was significantly associated with greater glycemic excursions and increased hypoglycemia in patients with TIR > 70%. Our findings indicate that HGI is a reliable predictor of hypoglycemia in this population.

Risk of hypoglycemia in type 1 diabetes management: An in-silico sensitivity analysis to assess and rank the quantitative impact of different behavioral factors

Background and Objective: In type 1 diabetes (T1D), a quantitative evaluation of the impact on hypoglycemia of suboptimal therapeutic decision (e.g. incorrect estimation of the ingested carbohydrates, inaccurate insulin timing, etc) is unavailable. Clinical trials to measure sensitivity to patient actions would be expensive, exposed to confounding factors and risky for the participants. In this work, a T1D patient decision simulator (T1D-PDS), realistically reproducing blood glucose dynamics in a large virtual population, is used to perform extensive in-silico trials and the so-derived data employed to implement a sensitivity analysis that ranks different behavioral factors based on their impact on a clinically meaningful parameter, the time below range (TBR). Methods: Eleven behavioral factors impacting on hypoglycemia are considered. The T1D-PDS was used to perform multiple 2-week simulations involving 100 adults, by testing about 3500 different perturbations for nominal behavior. A local linear approximation of the function linking the TBR and the factors were computed to derive sensitivity indices (SIs), quantifying the impact of each factor on TBR variations. Results: The obtained ranking quantifies importance of factors w.r.t. the others. Factors apparently related to hypoglycemia were correctly placed on the top of the ranking, including systematic (SI=2.05%) and random (SI=1.35%) carb-counting error, hypotreatment dose (SI=-1.21%), insulin bolus time w.r.t. mealtime (SI=1.09%). Conclusions: The obtained SIs allowed to rank behavioral factors based on their impact on TBR. The behavioral factors identified as most influential can be prioritized in patient training.

Hypoglycemia Incidence Rate in National and Non-National Health Insurance of Type 2 Diabetes Patients in COVID-19 Pandemic at Central Borneo

Community activity restrictions during the COVID-19 pandemic in Indonesia impact the quantity and quality of health services for type 2 diabetes (T2DM). This limitation could increase the risk of hypoglycemia in type 2 diabetes patients. The study aimed to compare the incidence rate of hypoglycemia between national (NHIP) and non-national health insurance participants (N-NHIP) with T2DM during the COVID-19 pandemic in Indonesia. The study used a cross-sectional design and was conducted at a government hospital in Central Borneo. Data was collected by consecutive sampling from September to November 2021. Sixty-two participants were divided into two groups (NHIP and N-NHIP groups). Each group consisted of 31 participants. They were interviewed regarding their experience with hypoglycemia in the last three months. The incidence rate of hypoglycemia in N-NHIP was higher than in NHIP (93.55% vs. 87.10%; p>0.05). Hypoglycemia is mostly presented in patients using a combination of short-acting and long-acting insulin. The incidence rate of hypoglycemia in T2DM during the COVID-19 pandemic in Central Borneo was relatively high. In future studies, it is necessary to analyse the factors that significantly affect the incidence of hypoglycemia in the population of T2DM patients in Indonesia.

A Randomized Controlled Trial of R-Form Verapamil Added to Ongoing Metformin Therapy in Patients with Type 2 Diabetes

ContextThere is a medical need for effective insulin-independent antidiabetic drugs that can promote pancreatic β-cell function and have a low risk of hypoglycemia in type 2 diabetes mellitus (T2DM) patients. R-form verapamil (R-Vera), which is able to enhance the survival of β-cells and has higher cardiovascular safety margin compared with racemic verapamil, was developed as a novel approach for T2DM treatment.ObjectiveThis randomized, double-blind, placebo-controlled clinical trial was designed to evaluate the efficacy and safety of 3 dosages of R-Vera added to ongoing metformin therapy in T2DM patients who had inadequate glycemic control on metformin alone.MethodsParticipants were randomly assigned in an equal ratio to receive R-Vera 450, 300, or 150 mg per day, or matching placebo, in combination with metformin. The primary endpoint was change in hemoglobin A1c (HbA1c) after 12 weeks of treatment.ResultsA total of 184 eligible participants were randomized to receive either R-Vera or placebo plus metformin. At week 12, significant reductions in HbA1c were observed for R-Vera 300 mg/day (−0.36, P = 0.0373) and 450 mg/day (−0.45, P = 0.0098) compared with placebo. The reduction in HbA1c correlated with decreasing fasting plasma glucose levels and improved HOMA2-β score. Treatment with R-Vera was well tolerated with no hypoglycemic episodes occurring during the trial.ConclusionAddition of R-Vera twice daily to ongoing metformin therapy significantly improved glycemic control in T2DM patients. The favorable efficacy and safety profile of R-Vera 300 mg/day can be considered as the appropriate dose for clinical practice.

1211-P: Associations of C-peptide, HOMA2, and GADA with Insulin Initiation and Risk of Hypoglycemia in Type 2 Diabetes

Background: In patients with type 2 diabetes (T2D) and non-ketotic presentation, low C-peptide (CP) and positivity for glutamic acid decarboxylase antibodies (GADA+) indicate early insulin requirement. In GADA- patients, the associations of CP with insulin use, glycemic response and severe hypoglycemia event (SHE) are unknown. Methods: We measured fasting CP and GADA in 4590 Chinese patients with T2D enrolled in the Hong Kong Diabetes Register in 1995-2012 followed up till 2019. The updated homeostasis model assessment (HOMA2) was derived from fasting CP and plasma glucose. We defined incident insulin use as the first insulin prescription of at least 28 days, glycemic response as HbA1c reduction at one year after insulin initiation, and SHE using ICD-9 codes. Linear and Cox regression models were applied for association analyses. Results: At enrolment, 32% had low CP (<250 pmol/L) and 5% were GADA+. In the low CP group, 7% were GADA+. In the GADA+ group, 50% had low CP. During a mean follow-up of 10.8 years, 58.6% were started on insulin after a median of 6.5 years. The GADA+ group was more likely to initiate insulin [adjusted HR (95% CI) 1.55 (1.26-1.91) ] and experienced SHE [HR 1.45 (1.08-1.95) ] than the GADA- group. In the GADA- group, low CP had lower hazards of insulin use [HR 0.86 (0.77-0.97) ] than high CP especially in patients with HOMA2-IR (insulin resistance) above median. The low CP group had higher HR of 1.34 (1.13-1.59) of SHE than the high CP group. In the GADA+ group, low CP was associated with increased risk of SHE [HR 1.81 (1.25, 2.62) ] but not in patients with high CP (P interaction= 0.01) . Both CP and GADA did not predict glycemia response after controlling for baseline HbA1c. Conclusions: In patients with T2D, CP interacted with GADA to influence disease progressions including early insulin therapy and SHE. C-peptide might be correlated with IR in patients with GADA-. These subphenotypes allowed more precise classification of beta cell function to guide personalized treatment. Disclosure B.Fan: None. A.Luk: None. J.C.Chan: Board Member; Asia Diabetes Foundation, Consultant; Bayer AG, Boehringer Ingelheim International GmbH, Celltrion, Merck Sharp & Dohme Corp., Roche Diabetes Care, Viatris Inc., Research Support; Applied Therapeutics, AstraZeneca, Eli Lilly and Company, Hua Medicine, Servier Laboratories, Stock/Shareholder; GemVCare Ltd. E.S.H.Lau: None. H.Wu: None. M.Shi: None. A.Yang: None. C.K.P.Lim: None. A.P.Kong: Advisory Panel; Abbott, Kyowa Kirin Co., Ltd., Other Relationship; AstraZeneca, Novo Nordisk, Research Support; Boehringer Ingelheim, Speaker's Bureau; AstraZeneca, Bayer, Eli Lilly and Company, Sanofi, Stock/Shareholder; Aptorum Group Limited. E.Chow: Research Support; Hua Medicine, Medtronic, Powder Pharmaceuticals Inc., Speaker's Bureau; Novartis AG, Sanofi. R.C.Ma: Other Relationship; Bayer AG, Boehringer Ingelheim International GmbH, Research Support; AstraZeneca, Bayer AG, Novo Nordisk A/S, Pfizer Inc., Tricida, Inc. Funding The HKG Health Medical and Research Fund and RGC Research Impact Fund

Positive impact of pre-Ramadan education on glycemic control and reducing risk of hypoglycemia in type 2 diabetic elderly patients during COVID 19 pandemic

BackgroundElderly patients have higher risks for complications during Ramadan fasting. Educating patients is essential for fasting safely. AimTo evaluate the impact of pre-Ramadan education in reducing risk of hypoglycemia and achieving glycemic control in elderly. MethodsA prospective study carried out in outpatients clinics of Internal Medicine department in Assiut university hospital. It included 316 type 2 diabetic patients who intended to fast. They were grouped into 2 groups; < 65 years and ≥ 65 years patients. The patients received pre-Ramadan individual education sessions. A semi-structured questionnaire was used to collect the data to stratify the risk of fasting. The study was carried out in 3 phases. Assessment of hypoglycemia and biochemical parameters after the education was the primary outcome. ResultsFasting blood glucose decreased during and after Ramadan in elderly significantly (p = 0.0001). The patients who achieved fasting blood glucose less than 8 mmol/L increased from 29.3% to 46.6% after Ramadan in elderly patients. HbA1c decreased significantly after Ramadan (p = 0.001). The main cause of breaking fast was hypoglycemia in both groups; 9% vs.7.7% in patients < 65 and ≥ 65 years respectively. The waist circumference showed significant decrease in patient with 65 years old or more (p = 0.05). Total cholesterol and LDL increased with no statistical significance in patients ≥ 65 years (p = 0.512, 0.470). Both groups showed improvement of HDL cholesterol during and after Ramadan (P = 0.0001). ConclusionPre-fasting education had positive impact on decreasing the risk of symptomatic hypoglycemia in elderly diabetic patients.

Flexible insulin therapy improves metabolic control and decreases the risk of hypoglycemia in type 1 diabetic patients.

Introductionflexible insulin therapy (FIT) is considered as a crucial turning point in the management of type 1 diabetes. The purpose of this study was to evaluate the impact of this optimum therapeutic approach on improving metabolic control and decreasing hypoglycemic events in patients with type 1 diabetes.Methodsthirty-seven type 1 diabetic patients were included in a five days training programme of FIT. They had an HbA1c between 7.5 and 10%. Those patients were enrolled in a flexible insulin program and we evaluate clinical and metabolic parameters (glycated haemoglobin (HbA1c), hypoglycemic events, body mass index (BMI) and the rate of blood glucose measurements) before the course of FIT and 3, 6 and 9 months after the course.Resultsover a 9 months period of the study, the frequency of mild hypoglycemia decreased from 11.7 to 1.7 episodes/3 months (p = 0.005). The baseline HbA1c value improved by 1% at 3 months with an increase of 0.2% at 6 months, which remained unchanged at 9 months (p = <0.0001). Patients who were poorly controlled (HbA1c ≥ 8%) improved their baseline HbA1c value from 9.2% to 8.0% (p = <0.0001).Conclusionthe present study confirms that a structured training programme for FIT improves glycemic control and decreases hypoglycemic events in patients with type 1 diabetes and it can be adopted in countries with weak or intermediate income (e.g. Morocco), which allows those patients to take advantages of this therapeutic approach.

Estimation of Blood Glucose Concentration During Endurance Sports

In this paper, we describe a new statistical approach to estimate blood glucose concentration along time during endurance sports based on measurements of glucose concentration in subcutaneous interstitial tissue. The final goal is the monitoring of glucose concentration in blood to maximize performance in endurance sports. Blood glucose concentration control during and after aerobic physical activity could also be useful to reduce the risk of hypoglycemia in type 1 diabetes mellitus subjects. By means of a low invasive technology known as "continuous glucose monitoring", glucose concentration in subcutaneous interstitial tissue can now be measured every five minutes. However, it can be expressed as function of blood glucose concentration along time by means of a convolution integral equation. In the training phase of the proposed approach, based on measurements of glucose concentration in both artery and subcutaneous interstitial tissue during physical activity, the parameters of the convolution kernel are estimated. Then, given a new subject performing aerobic physical activity, a deconvolution problem is solved to estimate glucose concentration in blood from continuous glucose monitoring measurements

Risk Factors for Hypoglycemia in Inpatients with Total Parenteral Nutrition and Type 2 Diabetes: A Post HOC Analysis of the Insupar Study

Objective: Treatment of hyperglycemia with insulin is associated with increased risk of hypoglycemia in type 2 diabetes mellitus (T2DM) patients receiving total parenteral nutrition (TPN). The aim of this study was to determine the predictors of hypoglycemia in hospitalized T2DM patients receiving TPN. Methods: Post hoc analysis of the INSUPAR study, which is a prospective, open-label, multicenter clinical trial of adult inpatients with T2DM in a noncritical setting with indication for TPN. Results: The study included 161 patients; 31 patients (19.3%) had hypoglycemic events, but none of them was severe. In univariate analysis, hypoglycemia was significantly associated with the presence of diabetes with end-organ damage, duration of diabetes, use of insulin prior to admission, glycemic variability (GV), belonging to the glargine insulin group in the INSUPAR trial, mean daily grams of lipids in TPN, mean insulin per 10 grams of carbohydrates, duration of TPN, and increase in urea during TPN. Multiple logistic regression analysis showed that the presence of diabetes with end-organ damage, GV, use of glargine insulin, and TPN duration were risk factors for hypoglycemia. Conclusion: The presence of T2DM with end-organ damage complications, longer TPN duration, belonging to the glargine insulin group, and greater GV are factors associated with the risk of hypoglycemia in diabetic noncritically ill inpatients with parenteral nutrition. Abbreviations: ADA = American Diabetes Association; BMI = body mass index; CV% = coefficient of variation; DM = diabetes mellitus; GI = glargine insulin; GV = glycemic variability; ICU = intensive care unit; RI = regular insulin; T2DM = type 2 diabetes mellitus; TPN = total parenteral nutrition.

Respective Contributions of Glycemic Variability and Mean Daily Glucose as Predictors of Hypoglycemia in Type 1 Diabetes: Are They Equivalent?

To evaluate the respective contributions of short-term glycemic variability and mean daily glucose (MDG) concentration to the risk of hypoglycemia in type 1 diabetes. People with type 1 diabetes (n = 100) investigated at the University Hospital of Montpellier (France) underwent continuous glucose monitoring (CGM) on two consecutive days, providing a total of 200 24-h glycemic profiles. The following parameters were computed: MDG concentration, within-day glycemic variability (coefficient of variation for glucose [%CV]), and risk of hypoglycemia (presented as the percentage of time spent below three glycemic thresholds: 3.9, 3.45, and 3.0 mmol/L). MDG was significantly higher, and %CV significantly lower (both P < 0.001), when comparing the 24-h glycemic profiles according to whether no time or a certain duration of time was spent below the thresholds. Univariate regression analyses showed that MDG and %CV were the two explanatory variables that entered the model with the outcome variable (time spent below the thresholds). The classification and regression tree procedure indicated that the predominant predictor for hypoglycemia was %CV when the threshold was 3.0 mmol/L. In people with mean glucose ≤7.8 mmol/L, the time spent below 3.0 mmol/L was shortest (P < 0.001) when %CV was below 34%. In type 1 diabetes, short-term glycemic variability relative to mean glucose (i.e., %CV) explains more hypoglycemia than does mean glucose alone when the glucose threshold is 3.0 mmol/L. Minimizing the risk of hypoglycemia requires a %CV below 34%.

Addition of canagliflozin to insulin improves glycaemic control and reduces insulin dose in patients with type 2 diabetes mellitus: A randomized controlled trial.

The aim of this study was to evaluate the efficacy of canagliflozin in reducing the required insulin dose and the risk of hypoglycaemia in type 2 diabetes (T2D). This study was conducted in patients with T2D treated with insulin. They were randomly assigned to the control (n = 17) and canagliflozin (n = 17, plus 100 mg/day canagliflozin) groups. In both groups, a defined insulin dose adjustment protocol was applied to achieve the same level of glycaemic control. The change from baseline in daily insulin dose was significantly smaller in the canagliflozin group (3.9 units/day) than in the control group (13.4 units/day; P = 0.040). Low blood glucose index and predicted % of blood glucose (BG) <70 mg/dL, which are hypoglycaemia-related variables, worsened significantly in the control group but both remained unchanged in the canagliflozin group. The standard deviation for night-time BG levels improved significantly only in the canagliflozin group. Supplementation of insulin therapy with 100 mg canagliflozin in patients with T2D reduced the required insulin dose and hypoglycaemic risk and flattened night-time glycaemic fluctuations while maintaining the same level of glycaemic control.

Are fast insulin analogues fast enough? Switching to faster aspart may reduce glycemic variability and the risk of hypoglycemia in type 1 diabetic patients on sensor-augmented insulin pump therapy

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Day-to-day fasting self-monitored blood glucose variability is associated with risk of hypoglycaemia in insulin-treated patients with type 1 and type 2 diabetes: A post hoc analysis of the SWITCH Trials.

AimsTo investigate the association between day‐to‐day fasting self‐monitored blood glucose (SMBG) variability and risk of hypoglycaemia in type 1 (T1D) and type 2 diabetes (T2D), and to compare day‐to‐day fasting SMBG variability between treatments with insulin degludec (degludec) and insulin glargine 100 units/mL (glargine U100).Materials and MethodsData were retrieved from two double‐blind, randomized, treat‐to‐target, two‐period (32 weeks each) crossover trials of degludec vs glargine U100 in T1D (SWITCH 1, n = 501) and T2D (SWITCH 2, n = 720). Available fasting SMBGs were used to determine the standard deviation (SD) of day‐to‐day fasting SMBG variability for each patient and the treatment combination. The association between day‐to‐day fasting SMBG variability and overall symptomatic, nocturnal symptomatic and severe hypoglycaemia was analysed for the pooled population using linear regression, with fasting SMBG variability included as a three‐level factor defined by population tertiles. Finally, day‐to‐day fasting SMBG variability was compared between treatments.ResultsLinear regression showed that day‐to‐day fasting SMBG variability was significantly associated with overall symptomatic, nocturnal symptomatic and severe hypoglycaemia risk in T1D and T2D (P < 0.05). Day‐to‐day fasting SMBG variability was significantly associated (P < 0.01) with all categories of hypoglycaemia risk, with the exception of severe hypoglycaemia in T2D when analysed within tertiles. Degludec was associated with 4% lower day‐to‐day fasting SMBG variability than glargine U100 in T1D (P = 0.0082) and with 10% lower day‐to‐day fasting SMBG variability in T2D (P < 0.0001).ConclusionsHigher day‐to‐day fasting SMBG variability is associated with an increased risk of overall symptomatic, nocturnal symptomatic and severe hypoglycaemia. Degludec has significantly lower day‐to‐day fasting SMBG variability vs glargine U100.

The Role of Diabetes Educators in Reduction the Risk of Hypoglycemia in Type 1 Patients during Fasting Ramadan

Background/Objectives: Fasting Ramadan for type 1 patients could be a challenging for both patients and physicians due to complications such as hypoglycemia, so in this study we choice to introduce glucose sensor and intensify the role of diabetes educator follow-up for type 1 patients who already on pump and willing to fast Ramadan for the first time. Design and Methods: This is a pilot prospective cohort study. Total of 6 patients (4 females and 2 males) with type 1 diabetes were recruited. Their mean age is (21.8+/-2.2) years, diabetes duration(11.1+/-2.3) years, mean duration on insulin pump is (4+/-1.6)years. Insulin basal rates of infusion were reduced 5-10% during fasting hours and increased between 5-10% after breaking fast. Weekly follow-up visits during Ramadan took place as well a daily follow-up by phone with the educator. Patients were asked to wear glucose sensor for entire days of fasting to detect hypoglycemia. Results: An (28.8+/- 8.6) units for 24 hours of basal insulin were set before fasting, and (26.8+/- 7.5) units for 24 hours of basal insulin were required for fasting Ramadan, and from that (15.1+/-4.3) units was basal insulin for total hours of fasting(14 hours), part of it explained by food habitus and lack of activity during Ramadan. An average of blood glucose was (11.1+/-2.1) mmol/l an hour before futoor, (9.7+/-3.8) mmol/l two hours after futoor, and (12.5+/- 3.4) mmol/l at suhoor. On the first week, four hypoglycemic episodes (BG less than 3.9 mmol/l), daily follow-up by diabetes educator, pop up visit in educator office and weekly visit to physician and educator office reduce the episode of hypoglycemia by the 2nd week till the 4th week of Ramadan. Conclusions: The use of glucose sensor together with adjustment of basal insulin wasn’t enough to minimzing the fear of fasting Ramadan but with role of diabetes educator reduce the risk of further hypoglycemia episode. Disclosure S. Mourad: None.

Different Indexes of Glycemic Variability as Identifiers of Patients with Risk of Hypoglycemia in Type 2 Diabetes Mellitus.

Recent publications frequently introduce new indexes to measure glycemic variability (GV), quality of glycemic control, or glycemic risk; however, there is a lack of evidence supporting the use of one particular parameter, especially in clinical practice. A cohort of type 2 diabetes mellitus (T2DM) patients in ambulatory care were followed using continuous glucose monitoring sensors (CGM). Mean glucose (MG), standard deviation, coefficient of variation (CV), interquartile range, CONGA1, 2, and 4, MAGE, M value, J index, high blood glucose index, and low blood glucose index (LBGI) were estimated. Hypoglycemia incidence (<54 mg/dl) was calculated. Area under the curve (AUC) was determined for different indexes as identifiers of patients with risk of hypoglycemia (IRH). Optimal cutoff thresholds were determined from analysis of the receiver operating characteristic curves. CGM data for 657 days from 140 T2DM patients (4.69 average days per patient) were analyzed. Hypoglycemia was present in 50 patients with 144 hypoglycemic events in total (incidence rate of 0.22 events per patient/day). In the multivariate analysis, both CV (OR 1.20, 95% CI 1.12-1.28, P < .001) and LBGI (OR 4.83, 95% CI 2.41-9.71, P < .001) were shown to have a statistically significant association with hypoglycemia. The highest AUC were for CV (0.84; 95% CI 0.77-0.91) and LBGI (0.95; 95% CI 0.92-0.98). The optimal cutoff threshold for CV as IRH was 34%, and 3.4 for LBGI. This analysis shows that CV can be recommended as the preferred parameter of GV to be used in clinical practice for T2DM patients. LBGI is the preferred IRH between glycemic risk indexes.

Fasting during Ramadan: efficacy, safety, and patient acceptability of vildagliptin in diabetic patients.

Diabetes management during Ramadan fasting is challenging to the physician in terms of minimizing the risk of hypoglycemia. As compared to oral hypoglycemic agents (OHAs) and sulfonylureas (SUs), which carry a higher and significant risk of hypoglycemia, newer antidiabetic agents such as dipeptidyl peptidase-4 (DPP-4) inhibitors have demonstrated lower risk of hypoglycemia during Ramadan fasting, with better patient compliance. In addition to diabetes education and pre-Ramadan assessments, the physician should also consider use of DPP-4 inhibitors (such as vildagliptin) during Ramadan fasting to minimize the risk of hypoglycemia in type 2 diabetic subjects. Severe episodes of hypoglycemia have been demonstrated in recent research and clinical trials with OHAs/SUs. Conversely, these research observations have also demonstrated comparative safety and efficacy with lower risk of hypoglycemia associated with vildagliptin. Current research review has collected evidence-based clinical trials and observations for the drug vildagliptin to minimize the risk of hypoglycemia during Ramadan fasting, while at the same time focusing the role of diabetes self-management education (DSME), pre-Ramadan assessments, and patient care.

Unsupervised overnight closed loop insulin delivery during free living: analysis of randomised cross-over home studies in adults and adolescents with type 1 diabetes

BackgroundThe closed-loop system (artificial pancreas) delivers insulin in a glucose-responsive manner by the use of a control algorithm that automatically directs insulin delivery, based on real-time sensor glucose concentrations. Results from hospital-based studies have shown improved overnight glucose control and reduced risk of hypoglycaemia in type 1 diabetes. We aimed to assess whether unsupervised closed-loop systems can provide a realistic treatment option in patients with type 1 diabetes. MethodsWe combined data from two open-label, phase 2, randomised, cross-over, unsupervised home trials of people with type 1 diabetes, one in 24 adults (mean age 43 years [SD 12], HbA1c 8·0% [0·9]) and the other in 16 adolescents (15·6 [3·6], 8·1 [0·8]). In each trial, after training on study devices, participants were allocated to two periods of sensor-augmented pump therapy either with or without overnight closed loop that used a model predictive control algorithm to direct insulin delivery. Allocation sequence was done with a computer-generated random code. Each period lasted 4 weeks in adults and 3 weeks in adolescents. Primary outcome for both trials was time when sensor glucose was in the target range (3·9–8·0 mmol/L). Analysis was by intention to treat. Participants (or parents) gave written informed consent. The trials are registered with ClinicalTrials.gov, numbers NCT01440140 and NCT01221467. FindingsClosed loop was started by participants on their own volition on 866 (89%) of 978 nights. The proportion of time when sensor glucose was in the target range between 0000 h and 0800 h was increased by a mean of 18·4% (95% CI 13·5–23·4, p<0·0001) during closed loop compared with no closed loop. Closed loop significantly reduced mean overnight sensor glucose by 0·9 mmol/L (95% CI 0·4–1·3, p=0·0001), and reduced the proportion of time when sensor glucose values were suggestive of hyperglycaemia (>8·0 mmol/L) (15·9%, 10·7–21·0; p<0·0001) and hypoglycaemia (<3·9 mmol/L) (median 0·9, IQR 0·2–2·2; p=0·014). Lower mean overnight glucose was associated with increased overnight insulin delivery (p<0·0001) without changing total daily insulin amount (p=0·84). InterpretationExtended use of overnight closed loop at home without supervision is feasible in adults and adolescents with type 1 diabetes. Clinically significant reduction in overnight glucose was observed accompanied by reduced time spent by patients in hypoglycaemia. To our knowledge, such combined effect has not been documented with any other means of intensified conventional insulin delivery. Longer term studies are warranted to assess its clinical potential. FundingDiabetes UK, Juvenile Diabetes Research Foundation, NIHR Cambridge Biomedical Research Centre.

Risk of hypoglycaemia in type 2 diabetes patients under different insulin regimens: a primary care database analysis.

Aims: To compare rates and predictors of documented hypoglycaemia in type 2 diabetes patients treated with either basal insulin supported oral therapy (BOT), conventional therapy (CT) or supplementary insulin therapy (SIT) in primary care.Methods: Data from 10,842 anonymous patients (mean age ± SD: 54 ± 8 yrs) on BOT, 2,407 subjects (56 ± 7 yrs) on CT, and 7,480 patients (52 ± 10 yrs) using SIT from 1,198 primary care practices were retrospectively analyzed (Disease Analyzer, Germany: 01/2005–07/2013). Stepwise logistic regression (≥1 documented hypoglycaemia: ICD code) was used to evaluate risk factors of hypoglycemia. Results: The unadjusted rates (95% CI) per 100 patient-years of documented hypoglycaemia were 1.01 (0.80–1.20) (BOT), 1.68 (1.10–2.30) (CT), and 1.61 (1.30–1.90) (SIT), respectively. The odds of having ≥1 hypoglycemia was increased for CT (OR; 95% CI: 1.71; 1.13–2.58) and SIT (1.55; 1.15–2.08) (reference: BOT). Previous hypoglycemia (OR: 11.24; 6.71–18.85), duration of insulin treatment (days) (1.06; 1.05–1.07), history of transient ischemic attack (TIA)/stroke (1.91; 1.04–3.50), and former salicylate prescriptions (1.44; 1.06–1.98) also showed an increased odds of having hypoglycemia. Higher age was associated with a slightly lower odds ratio (per year: 0.98; 0.97–0.99).Conclusions: Insulin naïve type 2 diabetes patients in primary care, initiated with CT and SIT have an increased risk of hypoglycaemia compared to BOT, which is in line with previous randomized controlled trials. As hypoglycaemic events are associated with an increased mortality risk, this real-world finding is of clinical relevance.

The Effect of Midday Moderate-Intensity Exercise on Postexercise Hypoglycemia Risk in Individuals With Type 1 Diabetes

Exercise increases the risk of hypoglycemia in type 1 diabetes. Recently we reported a biphasic increase in glucose requirements to maintain euglycemia after late-afternoon exercise, suggesting a unique pattern of delayed risk for nocturnal hypoglycemia. This study examined whether this pattern of glucose requirements occurs if exercise is performed earlier in the day. Ten adolescents with type 1 diabetes underwent a hyperinsulinemic euglycemic glucose clamp on 2 different occasions during which they either rested or performed 45 minutes of moderate-intensity exercise at midday. Glucose was infused to maintain euglycemia for 17 hours after exercise. The glucose infusion rate (GIR) to maintain euglycemia, glucose rates of appearance and disappearance, and levels of counterregulatory hormones were compared between conditions. GIRs to maintain euglycemia were not significantly different between groups at baseline (9.8 ± 1.4 and 9.5 ± 1.6 g/h before the exercise and rest conditions, respectively) and did not change in the rest condition throughout the study. In contrast, GIR increased more than 3-fold during exercise (from 9.8 ± 1.4 to 30.6 ± 4.7 g/h), fell within the first hour of recovery, but remained elevated until 11 hours after exercise before returning to baseline levels. The pattern of glucose requirements to maintain euglycemia in response to moderate-intensity exercise performed at midday suggests that the risk of exercise-mediated hypoglycemia increases during and for several hours after moderate-intensity exercise, with no evidence of a biphasic pattern of postexercise risk of hypoglycemia.

Increasing the Low-Glucose Alarm of a Continuous Glucose Monitoring System Prevents Exercise-Induced Hypoglycemia Without Triggering Any False Alarms

The use of continuous glucose monitoring systems (CGMSs) with low-glucose alarms is advocated as a means to decrease the risk of hypoglycemia in type 1 diabetes. Unfortunately, marked mismatches between CGMS readings and actual blood glucose (BG) concentrations limit the usefulness of CGMS in preventing hypoglycemia (1). Although we showed recently that raising the alarm level to compensate for this mismatch decreases the incidence and duration of hypoglycemic episodes, this results in an unacceptably high rate of false alarms (1), defined as an alarm triggered when BG levels are greater than the alarm threshold. This is an important issue because repeated exposure to false alarms can discourage individuals from using their CGMSs (2). Given that CGMSs overestimate BG levels when they rapidly decline (3,4), we propose that raising the CGMS alarm …