Glycaemic control and hypoglycaemia with insulin glargine 300 U/mL versus insulin glargine 100 U/mL in insulin-naïve people with type 2 diabetes: 12-month results from the EDITION 3 trial

AimTo explore if efficacy and safety findings for insulin glargine 300 U/mL (Gla-300) versus insulin glargine 100 U/mL (Gla-100), observed over 6 months in insulin-naïve people with type 2 diabetes, are maintained after 12 months.MethodsEDITION 3 was a phase 3a, randomized, multicentre, open-label, parallel-group, treat-to-target study of once-daily Gla-300 versus Gla-100 (target fasting self-monitored plasma glucose, 4.4–5.6 mmol/L [80–100 mg/dL]). Participants completing the initial 6-month treatment phase continued their previously allocated basal insulin.ResultsOf 878 participants randomized, 337/439 (77%) and 314/439 (72%) assigned to Gla-300 and Gla-100, respectively, completed 12 months of treatment. Improved glycaemic control was sustained until 12 months in both treatment groups, with similar reductions in HbA_1c from baseline to month 12 (difference: −0.08 [95% confidence interval (CI): −0.23 to 0.07] % or −0.9 [−2.5 to 0.8] mmol/mol). Relative risk of experiencing ≥ 1 confirmed (≤ 3.9 mmol/L [≤ 70 mg/dL]) or severe hypoglycaemic event with Gla-300 versus Gla-100 was 0.86 (95% CI: 0.69 to 1.07) at night and 0.92 (0.82 to 1.03) at any time of day. For events with a glycaemic threshold of < 3.0 mmol/L (< 54 mg/dL) these numbers were 0.76 (0.49 to 1.19) and 0.66 (0.50 to 0.88). A similar pattern was seen for documented symptomatic events. No between-group differences in adverse events were identified.ConclusionOver 12 months, Gla-300 treatment was as effective as Gla-100 in reducing HbA_1c in insulin-naïve people with type 2 diabetes, with lower overall risk of hypoglycaemia at the < 3.0 mmol/L threshold.     

Moderate intensity sports and exercise is associated with glycaemic control in women with gestational diabetes

AimTo assess the association of regular, unsupervised sports and exercise during pregnancy, by intensity level, with glycaemic control in women with gestational diabetes (GDM).MethodsProspective cohort study of 971 women who, shortly after being diagnosed with GDM, completed a Pregnancy Physical Activity Questionnaire assessing moderate and vigorous intensity sports and exercise in the past 3 months. Self-monitored capillary glucose values were obtained for the 6-week period following the questionnaire, with optimal glycaemic control defined ≥ 80% values meeting the targets < 5.3 mmol/L for fasting and < 7.8 mmol/L 1-hour after meals. Logistic regression estimated the odds of achieving optimal control; linear regression estimated activity level-specific least square mean glucose, as well as between-level mean glucose differences.ResultsFor volume of moderate intensity sports and exercise ([MET × hours]/week), the highest quartile, compared to the lowest, had significantly increased odds of optimal control (OR = 1.82 [95% CI: 1.06–3.14] P = 0.03). There were significant trends for decreasing mean 1-hour post breakfast, lunch and dinner glycaemia with increasing quartile of moderate activity (all P < 0.05). Any participation in vigorous intensity sports and exercise was associated with decreased mean 1-hour post breakfast and lunch glycaemia (both P < 0.05). No associations were observed for fasting.ConclusionHigher volumes of moderate intensity sports and exercise, reported shortly after GDM diagnosis, were significantly associated with increased odds of achieving glycaemic control. Clinicians should be aware that unsupervised moderate intensity sports and exercise performed in mid-pregnancy aids in subsequent glycaemic control among women with GDM.     

Accuracy assessment of online glucose monitoring by a subcutaneous enzymatic glucose sensor during exercise in patients with type 1 diabetes treated by continuous subcutaneous insulin infusion

AimOnline continuous glucose monitoring (CGM) during physical exercise would be highly useful in patients with insulin-treated diabetes. For this reason, this study assessed whether such a goal could be reached with a subcutaneous ‘needle-type’ enzymatic sensor.MethodsTen patients (five women/five men), aged 51 ± 12 years, with type 1 diabetes for 24 ± 11 years treated by continuous subcutaneous insulin infusion (CSII) for more than 1 year (HbA_1c: 7.5 ± 0.8%) performed a 30-min bout of exercise at a constant high-intensity load (15% above their individual ventilatory threshold) on a cycle ergometer. All patients wore a subcutaneous ‘needle-type’ enzymatic glucose sensor linked to a portable monitor (Guardian^® RT, Medtronic-MiniMed, Northridge, CA, USA) that had been inserted the previous evening. Sensor calibration was performed against capillary blood glucose immediately before the exercise. CGM values were recorded every 5 min from T_–10 to T₊₃₀, then every 10 min during the recovery period from T₊₃₀ to T₊₉₀. These recorded values were compared with blood glucose assays performed on simultaneously collected venous samples.ResultsSensor functioning and tolerability raised no problems except for one sensor that could not be adequately calibrated. Data from this patient were excluded from the data analysis. An average blood glucose decrease of 63 ± 63 mg/dL (3.5 ± 3.5 mmol/L) (median decrease: 58 mg/dL [3.22 mmol/L]; range: –3 mg/dL [0.16 mmol/L] to 178 mg/dL [9.8 mmol/L]) occurred during exercise bouts, while CGM values decreased by 38 ± 49 mg/dL (2.11 ± 2.72 mmol/L) (median: 32 mg/dL [1.7 mmmol/L]; range: –15 mg/dL [0.83 mmol/L] to 58 mg/dL [3.22 mmol/L]). Cumulative paired glucose values (n = 135) could be analyzed. The correlation factor between CGM and blood glucose values was 0.957 with an intercept of 0.275. The mean difference between paired values according to Bland–Altman analysis was 10 ± 31 mg/dL (0.56 ± 1.72 mmol/L). Clarke error grid analysis showed 91% of paired points in A and B zones, while 0%, 9% and 0% of paired points were in the C, D and E zones, respectively.ConclusionBlood glucose changes during intensive physical-exercise bouts performed by CSII-treated type 1 diabetes patients can be estimated with acceptable clinical accuracy by online CGM.     

The long-term effectiveness of metabolic control on cardiovascular disease in patients with diabetes in a real-world health care setting — A prospective diabetes management study

AimsTo determine the incidence rates of cardiovascular disease (CVD) and assess the effect of metabolic risk factor management on the development of CVD in patients with diabetes.MethodsWe studied 733 patients with diabetes without prior CVD in the Shanghai Taopu community health service center. Success in managing CVD risk factors was evaluated as follows: (1) glucose control (haemoglobin A1c [HbA1c] <7.0% in patients aged <65 years and <8.0% in patients aged ≥65 years), (2) blood pressure control (<140/90 mmHg), and (3) lipid control (high-density lipoprotein cholesterol ≥1.0 mmol/L in men and ≥1.3 mmol/L in women, and triglycerides <1.7 mmol/L).ResultsDuring a median 8.0-year follow-up, 206 CVD incident cases were identified. Each 1% increment in HbA1c, 10 mmHg increment in systolic blood pressure (SBP), and 1 mmol/L increment in triglycerides during follow-up significantly increased the risk of CVD by 17%, 37%, and 14%, respectively. Compared to those who did not, patients who met the blood pressure and glucose control goals during follow-up had a 64% and a 29% decreased risk of CVD, respectively. The multivariable-adjusted hazard ratios of CVD were 1.00, 1.78 (95% confidence interval [CI] 1.10–2.87), and 2.51 (95% CI 1.54–4.07) among patients who attained three, two, and one/none of the CVD factor control goals (HbA1c, blood pressure, and lipid) during follow-up, respectively.ConclusionsAverage levels of HbA1c, SBP, and triglycerides during follow-up were positively associated with the risk of CVD, and treatment targeting multiple factors can significantly reduce CVD risk.     

Association between post-dinner dietary intakes and nocturnal hypoglycemic risk in adult patients with type 1 diabetes

AimsTo describe (i) current bedtime nutritional practices and (ii) the association between post-dinner dietary intake and the occurrence of non-severe nocturnal hypoglycemia (NH) in real-life conditions among adult patients with type 1 diabetes using insulin analogs.MethodsOne hundred adults (median [interquartile range]: age 46.4 [36.0–55.8] years, HbA1c 7.9 [7.3–8.6] % (63 [56–70] mmol/mol)) using multiple daily injections (n = 67) or insulin pump (n = 33) wore a blinded continuous glucose monitoring system and completed a food diary for 72-h.ResultsNH occurred on 28% of 282 nights analyzed. (i) Patients reported post-dinner dietary intakes on 63% of the evenings. They injected rapid-acting insulin boluses on 64 occasions (23% of 282 evenings). These insulin boluses were mostly injected with (n = 37) dietary intakes. (ii) Post-dinner dietary intake was not associated with NH occurrence in univariate analyses. In multivariate analyses, the injection of rapid-acting insulin modulated the association between post-dinner dietary intake and NH: with insulin, post-dinner carbohydrate intake was positively associated with NH (odds ratio (OR): 1.16 [95% confidence interval, CI: 1.04–1.29] per 5 g increase, p = 0.008); without insulin, post-dinner protein intake was inversely associated with NH occurrence (OR [95% CI]: 0.88 [0.78–1.00] per 2 g increase, p = 0.048).ConclusionsNH remains frequent in adults with type 1 diabetes. There is a complex relationship between post-dinner dietary intake and NH occurrence, including the significant role of nutrient content and rapid-acting insulin injection that requires further investigation.     

A large proportion of prediabetes and diabetes goes undiagnosed when only fasting plasma glucose and/or HbA1c are measured in overweight or obese patients

AimsThe purposes of the study were to determine the prevalence of unrecognized dysglycaemia in overweight (body mass index [BMI] 25–29.9 kg/m²) and obese (BMI ≥30 kg/m²) patients, to assess the extent to which measures of fasting plasma glucose (FPG) and/or HbA_1c, compared with oral glucose tolerance tests (OGTTs), misdiagnose dysglycaemia, and to determine the factors associated with an isolated abnormal post-OGTT glucose value.MethodsOGTT was performed and HbA_1c was measured in 1283 inpatients with BMI scores ≥25 kg/m² and no history of dysglycaemia.ResultsPrediabetes was found in 257 (20.0%) subjects (197 with impaired glucose tolerance, 29 with impaired fasting glucose, 31 with both) and diabetes in 77 (6.0%), including 22 with FPG ≥7 mmol/L (WHO definition). The sensitivity of FPG >6 mmol/L, FPG >5.5 mmol/L, HbA_1c ≥6% and the recommendations of the French National Agency of Accreditation and Evaluation in Health Care (ANAES) to identify patients with abnormal OGTTs was 29.9, 41.3, 36.8 and 15.6%, respectively. The factors that were independently associated with diabetes in obese women with FPG <7 mmol/L were age (per 10 years: OR 1.54 [1.00–2.11]; P = 0.049) and FPG (OR 6.1 [1.4–30.0]; P = 0.014), whereas age (OR 1.26 [1.09–1.44]; P < 0.01) and waist circumference (per 10 cm: OR 1.17 [1.01–1.33]; P < 0.05) were independently associated with dysglycaemia in obese women with FPG <6.1 mmol/L.ConclusionIn overweight and obese patients: dysglycaemia is commonly seen; FPG alone, compared with OGTT, failed to diagnose 70% of dysglycaemia cases; FPG >5.5 mmol/L and HbA_1c ≥6.0% are not necessarily substitutes for OGTT; and older age and larger waist circumference should be used to select those obese women with normal FPG who might further benefit from OGTTs to diagnose dysglycaemia.     

Glycaemic control and hypoglycaemia with insulin glargine 300 U/mL compared with glargine 100 U/mL in Japanese adults with type 2 diabetes using basal insulin plus oral anti-hyperglycaemic drugs (EDITION JP 2 randomised 12-month trial including 6-month extension)

AimsTo compare insulin glargine 300 U/mL (Gla-300) with glargine 100 U/mL (Gla-100) in Japanese adults with uncontrolled type 2 diabetes on basal insulin and oral anti-hyperglycaemic drugs over 12 months.MethodsEDITION JP 2 was a randomised, open-label, phase 3 study. Following a 6-month treatment period, participants continued receiving previously assigned once daily Gla-300 or Gla-100, plus oral anti-hyperglycaemic drugs, in a 6-month extension period. Glycaemic control, hypoglycaemia and adverse events were assessed.ResultsThe 12-month completion rate was 88% for Gla-300 and 96% for Gla-100, with comparable reasons for discontinuation. Mean HbA_1c decrease from baseline to month 12 was 0.3% in both groups. Annualised rates of confirmed (≤ 3.9 mmol/L [≤ 70 mg/dL]) or severe hypoglycaemia were lower with Gla-300 than Gla-100 (nocturnal [00:00–05:59 h]: rate ratio 0.41; 95% confidence interval: 0.18 to 0.92; anytime [24 h]: rate ratio 0.64; 95% confidence interval: 0.44 to 0.94). Cumulative number of hypoglycaemic events was lower with Gla-300 than Gla-100. Adverse event profiles were comparable between treatments.ConclusionOver 12 months, Gla-300-treated participants achieved sustained glycaemic control and experienced less hypoglycaemia, particularly at night, versus Gla-100, supporting 6-month results.     

Hypertriglyceridemia is associated with development of metabolic glucose disorders,irrespective of glucose and insulin levels: A 15-year follow-up study

BackgroundBecause the role of 2-h postload glucose and insulin levels as confounders in the relationship between hypertriglyceridemia and development of metabolic glucose disorders (MGD) has not been elucidated, the aim of this study was to determine whether triglyceride levels ≥ 1.7 mmol/L are a risk factor of developing MGD in otherwise healthy men and women.MethodsA total of 341 healthy men and non-pregnant women, 30 to 50 years of age, were enrolled in a 15-year follow-up study and allocated into the exposed (triglycerides ≥ 1.7 mmol/L) and non-exposed (triglycerides < 1.7 mmol/L) groups. Follow-up visits were scheduled every 3 years to complete 5 visits (mean 3.8 visits). At final follow-up, about 15 years later (mean 13.6 years), contact was re-established in 236 individuals to complete 3540 person-years of follow-up. At baseline, all subjects in both groups were required to be free of impaired fasting glucose (IFG), impaired glucose tolerance (IGT), IFG + IGT, and type 2 diabetes.ResultsThe Poisson regression models, adjusted by age, sex, family history of diabetes, waist circumference, body mass index, total body fat, blood pressure, fasting and postload glucose, fasting and postload insulin, and HOMA-IR index, showed a significant association between triglycerides ≥ 1.7 mmol/L and IFG (relative risk – RR – 1.40; 95% CI 1.2–2.2), IGT (RR 1.60; 95% CI 1.3–2.2), IFG + IGT (RR 1.80; 95% CI 1.5–2.7), and type 2 diabetes (RR 3.0; 95% CI 2.5–3.8).ConclusionsSerum triglyceride levels ≥ 1.7 mmol/L are an independent risk factor of developing IFG, IGT, IFG + IGT, and type 2 diabetes in young and middle-aged, men and women.     

Multicentre randomized controlled trial with sensor-augmented pump vs multiple daily injections in hospitalized patients with type 2 diabetes in China: Time to reach target glucose

AimSensor-augmented pump (SAP) technology, which combines continuous subcutaneous insulin infusion (CSII) and real-time continuous glucose monitoring (RT-CGM), has been available for several years in China. In this study, the time required to reach predefined glycaemic targets with SAP vs multiple daily injection (MDI) therapy was compared in hospitalized patients with type 2 diabetes mellitus (T2DM).MethodsAdults (aged 18–65 years) with T2DM treated with insulin and admitted to hospital for glucose management were randomized to either SAP (Medtronic MiniMed™ Paradigm™ 722 system) or MDI with blinded CGM (Medtronic MiniMed CGMS System Gold™) for a 2-week period. Glycaemic targets were defined as three preprandial measurements between 80 and 130 mg/dL (4.4 and 7.2 mmol/L) and three 2-h postprandial measurements between 80 and 180 mg/dL (4.4 and 10.0 mmol/L) within the same day.ResultsWhen data from 81 patients (40 SAP, 41 MDI) were analysed, 21 patients using SAP therapy, compared with six using MDI therapy, achieved their glycaemic targets within 3 days, and their time to reach their glucose targets was significantly shorter (3.7 ± 1.1 vs 6.3 ± 3.1 days for MDI; P < 0.001), while three MDI patients failed to reach glycaemic targets within 14 days. SAP vs MDI patients experienced significantly less hypoglycaemia [sensor glucose < 50 mg/dL (2.8 mmol/L): 0.04% vs 0.32%, respectively; P < 0.05] and significantly less hyperglycaemia [sensor glucose > 180 mg/dL (10 mmol/L): 21.56% vs 35.03%, respectively; P < 0.05].ConclusionSAP vs MDI therapy in hospitalized patients with T2DM significantly reduced the time required to achieve glycaemic targets, and such systems may be a cost-effective way to improve glucose control and reduce hospital stays in T2DM patients.     

Treatment of reactive hypoglycemia with the macrobiotic Ma-pi 2 diet as assessed by continuous glucose monitoring: The MAHYP randomized crossover trial

Background and AimsNutritional therapy is recommended for management of reactive hypoglycemia (RH), a condition characterized by hypoglycemia that occurs within four hours after a meal. The macrobiotic Ma-Pi 2 diet improves glycemic control in subjects with type 2 diabetes. We explored the effect of this diet on outcomes in non-diabetic individuals with RH.Materials and MethodsTwelve subjects with RH were randomized to the Ma-Pi 2 diet for three days and a control diet for three days in a randomized crossover design. Subjects received snacks on two days out of each three-day period only, and were monitored using continuous glucose monitoring. The 24-h period was divided into daytime (08:00–22:30 h [subdivided into ‘daytime without snacks’ and ‘daytime with snacks’]) and night-time (22:31–07:59 h). The effects of the two diets on the number of RH events (blood glucose < 70 mg/dL [3.9 mmol/L]) and the percentage distribution of glucose readings within each of 16 glycemic intervals from < 40 mg/dL (2.2 mmol/L) to > 180 mg/dL (4.4 mmol/L) were determined.ResultsThere were significantly fewer RH events on the Ma-Pi 2 diet than the control diet during daytime without snacks (− 2.5 events; 95% CI: -7.5, 0.0; P = 0.022) and daytime with snacks (− 4.25 events; 95% CI: -7.5; − 2.0; P = 0.013) but no difference at night. The percentage of glucose readings in the interval 71–80 mg/dL (3.9–4.4 mmol/L) was significantly higher on the control diet during daytime with and without snacks (P = 0.03 for both), while the percentage of glucose readings in the interval 91–100 mg/dL (5.1–5.6 mmol/L) was significantly higher on the Ma-Pi 2 diet during daytime without snacks (P = 0.02).ConclusionsThe macrobiotic Ma-Pi 2 diet reduced blood glucose excursions during the day, thereby facilitating glycemic control in subjects with RH. The Ma-Pi 2 diet represents an effective nutritional tool for management of RH.     

The addition of pioglitazone in type 2 diabetics poorly controlled on insulin therapy: A meta-analysis

AimTo quantify the effect of a pioglitazone on glycemic control and lipid parameters, as well as the risk of adverse events when incorporated into the treatment regimen of patients with type 2 diabetes inadequately controlled on insulin.MethodsThe electronic databases PubMed, Embase and The Cochrance Library were searched systematically to identify randomized controlled trials (RCTs) of pioglitazone therapy in patients with type 2 diabetes mellitus (DM) inadequately controlled after treatment with insulin. Data on change of haemoglobin A1C (HbA1c), fasting plasma glucose (FPG), lipid parameters and risk of hypoglycemic, edema events were extracted from each study and pooled according to fixed effect model or random effect model in meta-analyses.ResultsFour RCTs including 1767 patients were included. The pooled estimate of change in HbA1c from baseline was 1.22% (95% CI 1.01–1.44, p < 0.001 vs. baseline) and of change in FPG from baseline was 1.63 mmol/l (95% CI 0.75–2.50, p < 0.001 vs. baseline). Pioglitazone significantly increased high-density lipoprotein cholesterol (HDL-c) level (0.2 mmol/L, 95%CI: 0.13–0.28) and low-density lipoprotein cholesterol (LDL-c) level (0.10 mol/L, 95%CI: 0.09–0.17), and lowered triglyceride (TG) level (0.05 mmol/L, 95%CI: 0.01–0.09). The odds of experiencing a hypoglycemic event in pioglitazone-treated arms was significantly higher than comparator treatments (RR = 1.57, 95% CI 1.12–2.20, p < 0.001). The case was the same with edema (RR = 2.42, 95% CI 1.67–3.50, p < 0.001).ConclusionsOur study implied that in patients with type 2 DM whose control is inadequate on insulin therapy, the additional pioglitazone could significantly improve glucose metabolism and might have a positive effect on important components of the lipid profile, which may have important implications in reducing the risk of cardiovascular disease, a major long-term complication in type 2 diabetes mellitus. Besides, the adverse events (AEs) were well tolerated.     

Efficacy and safety of basal insulin glargine 12 and 24 weeks after initiation in persons with type 2 diabetes: A pooled analysis of data from treatment arms of 15 treat-to-target randomised controlled trials

AimEvaluate early (0–12 weeks) and later (12–24 weeks) treatment outcomes in subjects with type 2 diabetes not achieving glycaemic control with oral antidiabetes drugs (OADs).MethodsSelected data were pooled from 15 randomised, controlled treat-to-target (fasting plasma glucose < 100 mg/dL [<5.6 mmol/L]) trials adding insulin glargine to metformin, a sulphonylurea, or both. Glycaemic and hypoglycaemia parameters, insulin dose, and body weight at weeks 12 and 24 were assessed using individualised subject-level data.ResultsData from 2837 subjects were analysed. HbA1c decreased from 8.8% (73 mmol/mol) at baseline by 1.4% (15 mmol/mol) at Week 12, and a further 0.2% (2 mmol/mol) at Week 24 in the pooled population. Similar reductions were observed across the different treatment groups. HbA1c < 7.0% (<53 mmol/mol) was reached by 34.8% of participants at Week 12 and an additional 24.3% by Week 24. Hypoglycaemia incidence and rates were similar during the early and continued treatment periods across all treatment combinations, but were markedly lower for insulin glargine plus metformin versus the other 2 regimens.ConclusionsEarly and sustained glycaemic benefits with a low-risk of hypoglycaemia are observed after initiation of insulin glargine in a pooled type 2 diabetes cohort previously uncontrolled on OADs.     

The consumption of bread enriched with betaglucan reduces LDL-cholesterol and improves insulin resistance in patients with type 2 diabetes

AimPrevious studies have shown that the water-soluble dietary fibre betaglucan, a natural component of oats, reduces cholesterol and postprandial hyperglycaemia. The aim of the present study was to investigate the effect of betaglucan-enriched bread consumption on the lipid profile and glucose homoeostasis of patients with type 2 diabetes (T2D).MethodsWe conducted a randomized, double-blind study in which 46 patients with T2D and LDL-C greater than 3.37 mmol/l (130 mg/dl) were randomized to incorporate into their diet, for 3 weeks, either bread enriched with betaglucan (providing 3 g/day of betaglucan) or white bread without betaglucan.ResultsThe consumption of bread containing betaglucan led to significant reductions (vs the control group) in LDL-C of 0.66 mmol/l (15.79%) versus 0.11 mmol/l (2.71%) (P = 0.009), in total cholesterol of 0.80 mmol/l (12.80%) versus 0.12 mmol/l (1.88%) (P = 0.006), in Fasting plasma insulin (FPI) of 3.23 μU/ml versus an increase of 3.77 μU/ml (P = 0.03) and in Homa-IR (Homoeostasis model assessment–insulin resistance) by 2.08 versus an increase of 1.33 (P = 0.04).ConclusionsBetaglucan enriched bread may contribute to the improvement of the lipid profile and insulin resistance in patients with T2D.     

Insulin detemir improves glycaemic control with less hypoglycaemia and no weight gain: 52-week data from the PREDICTIVE? study in a cohort of French patients with type 1 or type 2 diabetes

AimPREDICTIVE™ (an ongoing multinational observational study) provides an opportunity to explore the impact of insulin detemir use in routine clinical practice. Here, we report on long-term (52-week) data from a French cohort of patients (n = 1772), comprising 643 with type 1 diabetes and 1129 with type 2 diabetes.MethodsPatients were prescribed insulin detemir at their physician's discretion and assessed at various visits (baseline, 12 weeks, 26 weeks and 52 weeks). The primary endpoint was the frequency of serious adverse drug reactions, including major hypoglycaemia. Secondary endpoints included minor and nocturnal hypoglycaemia, glycaemic control (HbA_1c, fasting blood glucose and variability of fasting blood glucose) and weight change.ResultsThe incidence of serious adverse drug reactions was low throughout the study, seen in 10 patients with type 1 diabetes (14 events, 1.6%) and seven with type 2 diabetes (seven events, 0.6%). In both type 1 and type 2 diabetes cohorts, the overall minor and nocturnal hypoglycaemic events were reduced from baseline (P < 0.001), with no clinically significant changes in weight from baseline to endpoint. After 52 weeks of treatment with insulin detemir, glycaemic control improved, with reductions in: HbA_1c, by −0.6% and −0.8% in type 1 and type 2 diabetes patients, respectively; fasting blood glucose, by −1.4 mmol/L and −1.9 mmol/L respectively; and FBG variability, by −0.8 mmol/L and −0.3 mmol/L, respectively (P < 0.0001 for all).ConclusionPatients treated with insulin detemir in a clinical healthcare setting improved their glycaemic control with no increases in hypoglycaemia, adverse events or weight compared with baseline.     

Incidence of severe nocturnal hypoglycemia in patients with type 1 diabetes treated with insulin lispro or regular human insulin in addition to basal insulin glargine

Background and aimsOnce-daily (OD) basal insulin glargine (GLA) can be used as part of a multiple daily injection regimen in patients with type 1 diabetes mellitus. This randomized, multicenter study compared GLA + prandial regular human insulin (RHI) with GLA + prandial insulin lispro (LIS) in reducing the incidence of severe nocturnal hypoglycemia at endpoint. In addition, the effects on glycemic control of both treatments were investigated.Methods and resultsPatients (489) previously on neutral protamine Hagedorn (NPH) insulin or GLAR plus RHI/LIS were switched to, or continued on GLA (target fasting blood glucose [FBG] = 5.0–6.7 mmol/L [90–120 mg/dL]) for 8 weeks (qualification phase) prior to randomization; patients continued with their previous bolus insulin. Patients (n = 395) were then randomized to LIS (n = 193) or RHI (n = 202) and treated for 16 weeks. The proportion of patients experiencing severe nocturnal hypoglycemia at the end of the study was 1.55% (n = 3) in the RHI group and 1.11% (n = 2) in the LIS group (p = 0.938 between groups); the mean difference was 0.44% (95% CI: ?1.77, 2.21), suggesting non-inferiority of RHI versus LIS. At the end of the study, both treatments did not differ with respect to glycemic control, as measured by hemoglobin A_1c and FBG.ConclusionThese results suggest that GLA + LIS and GLA + RHI treatments were associated with a similar and low rate of severe nocturnal hypoglycemia. Further studies with greater patient sizes are necessary to verify the findings from the current study.     

Glucose flux in controlled hyperglycaemia before and after oral glucose ingestion in men with mild type 2 diabetes

AimsThis study aimed to determine how insufficiently suppressed endogenous glucose production vs. reduced peripheral glucose uptake contribute to postprandial hyperglycaemia in type 2 diabetes (T2D).MethodsEight men with T2D (age: 52 ± 7 years; BMI: 26.6 ± 2.3 kg/m²; fasting glycaemia: 7.1 ± 1.5 mmol/L) were compared with eight non-diabetic controls (age: 51 ± 5 years; BMI: 24.6 ± 2.9 kg/m²; fasting glycaemia: 4.9 ± 0.4 mmol/L). Their glucose turnover rates and hepatic glucose cycles were measured by monitoring [2H7]glucose infusion, with m+7 and m+6 enrichment, 3 h before and 4 h after the ingestion of [6,6-2H2]-labelled glucose, while maintaining glycaemia at 10 mmol/L using the pancreatic clamp technique.ResultsOf the 700 mg/kg oral glucose load, 71% appeared in the systemic circulation of the T2D patients vs. 63% in the controls (NS). Endogenous glucose production and hepatic glucose cycles did not differ from normal either before or after oral glucose ingestion, while peripheral glucose uptake was reduced by 40% in the T2D group both before (P < 0.01) and after (P < 0.05) ingestion of oral glucose.ConclusionWhen T2D patients were compared with non-diabetic subjects with similarly controlled levels of hyperglycaemia after oral glucose ingestion, they essentially differed only in peripheral glucose uptake, whereas endogenous glucose production was apparently unaltered.     

A systematic review and meta-analysis of exercise interventions in adults with type 1 diabetes

AimsConflicting evidence exists regarding the benefits of physical activity for long-term blood glucose control in adults with type 1 diabetes (T1D). The object of this systematic review was to determine the effects of physical activity on long-term blood glucose control in T1D adults.MethodsPubMed/Medline, Embase, CENTRAL, SPORTdiscus, Global Health and ICTRP were searched up to October 2013 for randomized trials of aerobic or resistance exercise training in T1D adults. Exercises had to be performed at least twice weekly for a minimum of two months. The primary outcome was glycated hemoglobin (HbA_1c). Secondary outcomes included cardiorespiratory fitness and insulin dose.ResultsSix randomized trials were identified (323 adults); sample sizes ranged from n = 6 to n = 148 participants receiving the intervention. Five trials had an unknown risk of bias; one trial was deemed to be at high risk of bias. Exercise frequency varied from twice weekly to daily, with intensities (50–90% VO_2peak), and session durations (20–120 min) varying widely. Four trials reported HbA_1c, which decreased with exercise training (mean difference [MD] −0.78% (−9 mmol/mol), 95% CI −1.14 (−13 mmol/mol) to −0.41 (−5 mmol/mol); p < 0.0001; I² 0%) compared with controls. Exercise training improved cardiorespiratory fitness by 3.45 ml/kg/min (95% CI 0.59 to 6.31, p = 0.02, I² 0%) compared with controls. One trial reported an effect on insulin dose (MD −0.4 U/kg, 95% CI −0.53 to −0.27, p < 0.00001) compared to controls.ConclusionThere are currently insufficient well-designed studies to ascertain the true effect of exercise training on HbA_1c in individuals with T1D, but current results are promising.     

Insulin glargine versus insulin degludec in patients failing on oral therapy in type 2 diabetes: A retrospective real world comparative data from India

ObjectiveTo compare the changes in various glycemic parameters in insulin-naïve type 2 diabetes mellitus (DM) patients who were initiated on insulin glargine or insulin degludec in a real world setting.MethodsRetrospective data were analyzed in consecutive type 2 DM patients in a real world setting, who failed oral therapy (at least 2 oral anti-diabetic drugs) and were initiated with either insulin glargine or insulin degludec. The parameters assessed were the changes in HbA1c, fasting plasma glucose, body weight, dose of Insulin and the total number of patient reported hypoglycemic episodes up to 6 months after initiation.ResultAt baseline, insulin glargine and insulin degludec groups were similar in terms of gender, age, weight, HbA1c and duration of diabetes. After 6 months follow up the change in HbA1c (−1.09 versus −1.45 P = 0.124), change in FPG (−72.81 mg/dl [−4mmol/L] versus −75.88 mg/dl [−4.2 mmol/L] P = 0.755), and the change in body weight (+1.65 versus +0.85 P = 0.082) were similar in glargine and degludec groups, respectively. Patients in insulin degludec group experienced significantly lesser patient reported hypoglycemic episodes (12 versus 40) and required significantly lesser dose (25.68 Units versus 18.61 Units per day; P = 0.002) compared to insulin glargine. 41% of the patients reached HbA1C target of ≤7% with insulin glargine compared to 69% with insulin degludec within the specified time period.ConclusionResults from this real world analysis suggest that among type 2 DM patients who were initiated on insulin degludec as compared to insulin glargine may be associated with significantly lesser patient reported hypoglycemic episodes and lesser dose of insulin while achieving similar glycemic control. This study is however limited by the retrospective nature of the data collection.     

High prevalence of diabetes mellitus and hospital-related hyperglycaemia in French general wards

AimThe study evaluated the in-hospital prevalence of diabetes and hospital-related hyperglycaemia in a variety of French general wards.MethodsThe multicentre cross-sectional study involving nine French hospitals measured venous fasting plasma glucose (FPG) on a single day in patients hospitalized in adult medical and surgical short-term wards. Diabetes status and length of stay were recorded.ResultsOf the 2141 inpatients included in the study, 355 (16.5%) had known diabetes, 156 (7.3%) had screened diabetes (FPG ≥ 7 mmol/L with no diabetes history), 515 (24.1%) had impaired fasting glucose (IFG; FPG 5.5–6.9 mmol/L) and 1115 (52.1%) had normal glucose values (FPG < 5.5 mmol/L). Diabetes prevalence varied from 11% in hospitals in the west of France to 21% in hospitals in northern and eastern regions. The highest known diabetes prevalence was observed in units for cardiovascular surgery (33%), infectious diseases (27%) and kidney disorders (26%). In cancer units, one-fifth of patients had screened diabetes and one-sixth had known diabetes. Among the known diabetes patients, 127 (36%) were already being treated with insulin, while an additional 41 (12%) started insulin therapy during their hospital stay. Patients with known and screened diabetes were older (70.8 ± 12.2 and 71.1 ± 15.6 years, respectively) than the normal-glucose patients (65.6 ± 18.9 years; P < 0.001). Average length of stay was no different between known diabetes and normal-glucose patients after adjusting for age (11.3 ± 7.7 vs 10.0 ± 7.4 days; NS).ConclusionOverall, metabolic glucose disorders (known or screened diabetes and IFG) were found in 48% of inpatients in various French hospital general wards.     

Equal improvement in glycaemia with lixisenatide given before breakfast or the main meal of the day

AimsThe aim of this study is to explore whether administration timing affects glycaemic control by lixisenatide once-daily in type 2 diabetes mellitus (T2DM).MethodsA phase IIIb, open-label, 1:1 randomized, active-controlled, 24-week multicentre study of T2DM patients inadequately controlled on metformin was conducted. Patients were administered lixisenatide before breakfast or the main meal. The primary endpoint was change from baseline at week 24 in glycated haemoglobin (HbA1c). Other endpoints: changes in body weight, fasting plasma glucose (FPG), 7-point self-monitored plasma glucose (SMPG) and Diabetes Treatment Satisfaction Questionnaire status (DTSQs) score. Adverse events (AEs) were monitored.ResultsMean change in HbA1c from baseline at week 24 was − 0.65% (− 7.1 mmol/mol; main meal) and − 0.74% (− 8.1 mmol/mol; breakfast). Mean changes in FPG, body weight and DTSQs score were comparable between groups. The mean change in body weight (kg) was − 2.60 (main meal) and − 2.80 (breakfast group). The 7-point SMPG profiles showed greatest reductions in postprandial glucose after the meal at which lixisenatide was administered, with a residual effect seen on the subsequent meal. AE rates were similar between groups, including gastrointestinal AEs.ConclusionsLixisenatide before the main meal was noninferior to lixisenatide before breakfast in patients insufficiently controlled on metformin. Lixisenatide treatment allows flexibility in administration timing.