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• Coefficients of variation (CVs) for glucose and HbA1c are key metrics for assessing short- and long-term variability in glucose homeostasis. • A threshold of 36 % for the CV glucose is recommended to separate stable from labile diabetes. • A CV glucose value of < 27 % reduces the risk for hypoglycaemia to a minimal level. • A CV HbA1c of < 5 % for the is proposed as a suitable approach to guarantee a long-term stability of glucose homeostasis. Near normal glycaemic control in diabetes consists to target daily glucose fluctuations and quarterly HbA1c oscillations in addition to overall glucose exposure. Consequently, the prerequisite is to define simple, and mathematically undisputable key metrics for the short- and long-term variability in glucose homeostasis. As the standard deviations (SD) of either glucose or HbA1c are dependent on their means, the coefficient of variation (CV = SD/mean) should be applied instead as it that avoids the correlation between the SD and mean values. A CV glucose of 36% is the most appropriate threshold between those with stable versus labile glucose homeostasis. However, when near normal mean glucose concentrations are achieved a lower CV threshold of <27 % is necessary for reducing the risk for hypoglycaemia to a minimal rate. For the long-term variability in glucose homeostasis, a CV HbA1c < 5 % seems to be a relevant recommendation for preventing adverse clinical outcomes. [ABSTRACT FROM AUTHOR]

Objective: The aim of the Iluvien Clinical Evidence study in the UK (ICE-UK) was to assess the real-world effectiveness of fluocinolone acetonide (FAc) 190 μg intravitreal implant for the treatment of clinically significant chronic diabetic macular edema (DME) in routine clinical practice. Methods: This retrospective study collected data from patient medical records in 13 ophthalmology centers for people with DME prescribed FAc intravitreal implant between April 1, 2013 and April 15, 2015. Visual acuity (VA) and intraocular pressure (IOP) measurements were collected for 12 months prior to and after implant. Results: Two hundred and eight people, contributing 233 eyes, treated with FAc implant were included. Mean age was 68.1 years and 62% were male. In the 12 months prior to FAc implant, VA declined. Median (interquartile range, IQR) VA was 0.66 (0.48–1.00) LogMAR units (equivalent to 52.0 ETDRS letters) at implant, improving to 0.60 (0.38–0.90) LogMAR units (55.0 letters) at 12 months post-implant (p<0.001). In total, 44%, 30%, and 18% of people achieved an improvement in ETDRS score of ≥5, ≥10, and ≥15 letters, respectively, over the same period. A small but significant (p<.001) increase in median IOP was observed (median = 15.0, IQR = 13.0–18.0 mmHg at implant to 18.0, 15.0–21.0 mmHg at 12 months). In the 12 months following implant, additional IOP-lowering therapy was prescribed in 15% of subjects previously not requiring such therapy. Conclusion: Following FAc implant, an overall significant improvement in VA was observed over a period of 12 months, accompanied by a significant but small increase in IOP. [ABSTRACT FROM AUTHOR]

Objective: To define the threshold for excess glucose variability (GV), one of the main features of dysglycemia in diabetes.Research Design and Methods: A total of 376 persons with diabetes investigated at the University Hospital of Montpellier (Montpellier, France) underwent continuous glucose monitoring. Participants with type 2 diabetes were divided into several groups-groups 1, 2a, 2b, and 3 (n = 82, 28, 65, and 79, respectively)-according to treatment: 1) diet and/or insulin sensitizers alone; 2) oral therapy including an insulinotropic agent, dipeptidyl peptidase 4 inhibitors (group 2a) or sulfonylureas (group 2b); or 3) insulin. Group 4 included 122 persons with type 1 diabetes. Percentage coefficient of variation for glucose (%CV = [(SD of glucose)/(mean glucose)] × 100) and frequencies of hypoglycemia (interstitial glucose <56 mg/dL [3.1 mmol/L]) were computed.Results: Percentages of CV (median [interquartile range]; %) increased significantly (P < 0.0001) from group 1 (18.1 [15.2-23.9]) to group 4 (37.2 [31.0-42.3]). In group 1, the upper limit of %CV, which served as reference for defining excess GV, was 36%. Percentages of patients with %CVs above this threshold in groups 2a, 2b, 3, and 4 were 0, 12.3, 19.0, and 55.7%, respectively. Hypoglycemia was more frequent in group 2b (P < 0.01) and groups 3 and 4 (P < 0.0001) when subjects with a %CV >36% were compared with those with %CV ≤36%.Conclusions: A %CV of 36% appears to be a suitable threshold to distinguish between stable and unstable glycemia in diabetes because beyond this limit, the frequency of hypoglycemia is significantly increased, especially in insulin-treated subjects. [ABSTRACT FROM AUTHOR]

Objectives:To compare retinal thickness before and after treatment with the fluocinolone acetonide (FAc) 190 µg intravitreal implant in people with diabetic macular edema (DME) using data from the Iluvien Clinical Evidence study in the UK (ICE-UK). Methods:For this retrospective cohort study, data on people attending any one of 13 participating ophthalmology departments and treated with FAc intravitreal implant between April 1, 2013 and April 15, 2015 were collected for 12 months prior to and at least 12 months after implantation. Cross-sectional and longitudinal patterns of central foveal thickness (CFT) were compared before and after FAc implant. Results:There were 208 people who contributed data from 233 individual eyes treated with the FAc implant. Mean age was 68.1 years and 62% were male. Median (interquartile range) CFT decreased from 462 µm (354–603 µm) at time of implant to 309 µm (222–433 µm) at 12 months post-implant (p < .001). Over the same period, a reduction of ≥10%, ≥25%, and ≥50% in CFT was observed in 113 (65%), 87 (50%), and 37 (21%) treated eyes, respectively. Eyes with a CFT of ≥400 µm at the time of implant were significantly more likely to achieve a reduction in CFT of ≥10%, ≥25%, and ≥50% at 12 months (allp < .001) compared with eyes with a CFT of <400 µm at implant. Both retinal thickness and changes in retinal thickness were loosely correlated with visual acuity. Conclusion:A marked reduction in retinal thickness was observed in people following FAc intravitreal implant for DME. The response was related to the degree of retinal thickness prior to treatment. [ABSTRACT FROM AUTHOR]

Objectives:To assess healthcare resource use and costs of treating people with clinically significant diabetic macular edema (DME) with fluocinolone acetonide (FAc) 190 µg intravitreal implant in routine clinical practice. Methods:The retrospective Iluvien Clinical Evidence (ICE-UK) study collected data on people prescribed the FAc implant in any one of 13 ophthalmology centers between April 1, 2013 and April 15, 2015. Data were collected for 12 months before and after implantation. Standard UK costs were attributed to healthcare resource use. Results:In total, 208 people contributing 233 FAc-treated eyes were selected. Mean age was 68.1 years and 62% were male. The mean (standard deviation, SD) number of anti-vascular endothelial growth factor (anti-VEGF) injections per FAc treated eye in the 12 months prior to implant was 2.8 (2.5), decreasing to 0.6 (1.4) for the same period after implant (p < .001). The corresponding figures for other steroid injections (dexamethasone and triamcinolone) were 0.14 (0.4) before and 0.08 (0.4) after implant (p = .016). There was no statistically significant difference in the number of laser therapies required in the 12 months before and after FAc implant (mean = 0.12 vs 0.11, respectively;p = .626). Overall, mean (SD) healthcare costs were £2,691 (£1,850) before and £1,239 (£1,203) after FAc implant (p < .001). The unit drug and administration cost per FAc implant was £5,680. Conclusions:Excluding the cost of the FAc implant, healthcare costs were significantly reduced in the 12 months post-implant. FAc implant has a duration of 3 years. This needs to be considered when interpreting the cost associated with the FAc implant. [ABSTRACT FROM AUTHOR]

Objectives:To compare visual and anatomical outcomes between eyes treated with fluocinolone acetonide (FAc) 190 µg intravitreal implant for clinically significant chronic diabetic macular edema (DME) and fellow eyes not treated with FAc implant using data from the Iluvien Clinical Evidence study in the UK (ICE-UK) study. Methods:In this retrospective cohort study, data on people attending hospital eye services and treated with the FAc implant between April 1, 2013 and April 15, 2015 were collected. Changes in visual acuity (VA), central foveal thickness (CFT) and intraocular pressure (IOP) were compared between study eyes (intervention) and fellow eyes. Results:A total of 208 people were selected. Mean age was 68.1 years and 62% were male. Mean change in VA was −0.09 LogMAR units for study eyes and 0.04 LogMAR units for fellow eyes at 12 months post-implant (p < .001). Over the same period, ≥5 letter, ≥10 letter and ≥15 letter improvements in Early Treatment Diabetic Retinopathy Study (ETDRS) score were achieved by more FAc treated eyes than by fellow eyes (41% versus 23%,p < .001; 28% versus 11%,p < .001; and 18% versus 4%,p < .001 at 12 months, respectively). Differences in the mean change in CFT (−113 µm versus −13 µm,p < .001) and IOP (3.2 mmHg versus −0.2 mmHg,p < .001) were also observed between study and fellow eyes at 12 months. Conclusion:Visual acuity improved in study eyes over the 12 months following FAc implant and worsened in fellow eyes. Over the same period, study eyes showed a larger improvement in central foveal thickness. Intraocular pressure worsened in study eyes only. Change in visual acuity, central foveal thickness and intraocular pressure between FAc implant and the end of the 12-month follow-up period differed significantly between study and fellow eyes. [ABSTRACT FROM AUTHOR]

The article discusses right screening time for diabetic retinopathy (DR) begin for children with type 1 diabetes. Topics discussed include visual impairment and blindness as a complication associated with diabetes, the American Academy of ophthalmology recommending for annual screening for all people with diabetes for more than five years and International Society for Pediatric and Adolescent Diabetes recommending screening for DR with two years of diabetes and from the age of 11 onwards.

OBJECTIVE--To assess the magnitude of the dawn phenomenon and its impact on the total glucose exposure in type 2 diabetes. RESEARCH DESIGN AND METHODS--A total of 248 noninsulin-treated persons with type 2 diabetes who underwent continuous glucose monitoring were divided into three groups selected by treatments: diet alone (n = 53); insulin sensitizers alone (n = 82); and insulin secreta-gogues alone or in combination with insulin sensitizers (n = 113). The dawn phenomenon (d glucose, mg/dL) was quantified by its absolute increment from nocturnal nadir to prebreakfast value. The participants were secondarily divided into two paired subsets after they had been separated by the presence/absence of a dawn phenomenon based on a threshold of 20 mg/dL and matched for glucose nadir. The impact of the dawn phenomenon was assessed on HbA1c and 24-h mean glucose. RESULTS--The median of d glucose (interquartile range) was 16.0 (0--31.5 mg/dL) in the 248 subjects, and no differences were observed across groups selected by HbA1c or treatments. In the overall population, the mean impacts on HbA1c and 24-h mean glucose were 4.3 ± 1.3 mmol/mol (0.39 6 0.12%) and 12.4 ± 2.4 mg/dL, respectively. The mean impact on 24-h mean glucose was not statistically different between those on diet alone (16.7 ± 5.9 mg/dL) compared with the two subsets treated with oral hypoglycemic agents (11.2 ± 5.3 and 8.5 ± 7.5 mg/dL). CONCLUSIONS--The impact of the dawn phenomenon on overall glycemic control in type 2 diabetes, as depicted by the HbA1c level, was ~0.4% and not eliminated by any of the currently available armamentarium of oral antidiabetes agents. [ABSTRACT FROM AUTHOR]

OBJECTIVE --To compare pharmacokinetics and pharmacodynamics of insulin analogs glargine and detemir, 24 subjects with type 1 diabetes (aged 38 ± 10 years, BMI 22.4 ± 1.6 kg/m², and A1C 7.2 ± 0.7%) were studied after a 2-week treatment with either glargine or detemir once daily (randomized, double-blind, crossover study). RESEARCH DESIGN AND METHODS -- Plasma glucose was clamped at 100 mg/dl for 24 h after subcutaneous injection of 0.35 unit/kg. The primary end point was end of action (time at which plasma glucose was >150 mg/dl). RESULTS -- With glargine, plasma glucose remained at 103 ± 3.6 mg/dl up to 24 h, and all subjects completed the study. Plasma glucose increased progressively after 16 h with detemir, and only eight subjects (33%) completed the study with plasma glucose < 180 mg/dl. Glucose infusion rate (GIR) was similar with detemir and glargine for 12 h, after which it decreased more rapidly with detemir (P < 0.001). Estimated total insulin activity (GIR area under the curve [AUC]O-end of GIR) was 1,412 ± 662 and 915 ± 225 mg/kg (glargine vs. detemir, P < 0.05), with median time of end of action at 24 and 17.5 h (glargine vs. detemir, P < 0.001). The antilipolytic action of detemir was lower than that of glargine (AUC free fatty acids0-24 h 11 ± 1.7 VS. 8 ± 2.8 mmol/l, respectively, P < 0.001). CONCLUSIONS -- Detemir has effects similar to those of glargine during the initial 12 h after administration, but effects are lower during 12-24 h. [ABSTRACT FROM AUTHOR]

A defect in the blue sensitive mechanism has been reported in certain ocular and systemic diseases. For example, tritanopic colour vision defects and changes to the S-cone electroretinogram (ERG) have been demonstrated in glaucoma and diabetes mellitus. Electrophysiological methods of eliciting the S-cone ERG, however, often result in considerable L- and M-cone intrusion. We report the findings of a study employing the silent substitution S-cone ERG technique, which is thought to represent an almost pure S-cone signal, and the L'Anthony desaturated D15 colour vision test in subjects with Type 1 or 2 diabetes mellitus with no or minimal background retinopathy. The results of this study show a significantly increased S-cone ERG b-wave implicit time and significantly worse colour vision in those with background retinopathy compared with those with no diabetic retinopathy. This suggests that S-cone pathway dysfunction may be responsible for the deterioration in colour vision found in diabetes mellitus. [ABSTRACT FROM AUTHOR]

OBJECTIVE -- Patients with diabetes commonly have a greater degree of anemia for their level of renal impairment than those presenting with other causes of renal failure. To clarify the contribution and differing roles of diabetes and nephropathy in the development of anemia in diabetic patients, we examined the hematologic and hematinic parameters of diabetic patients without nephropathy. RESEARCH DESIGN AND METHODS -- The study group was comprised of 62 patients with type 2 diabetes who had been followed for a median of 7 years. For the study, these patients had additional samples taken during their annual routine blood testing for the measurement of extra parameters, including serum ferritin, serum erythropoietin (Epo) levels, and the percentage of reticulocytes. These measurements were combined with the routine parameters Hb, hematocrit, HbA[sub 1c], and glomerular filtration rate. RESULTS -- In all, 8 of the 45 male patients (17.8%) and 2 of the 17 female patients (11.8%) were classified as anemic (Hb <13g/dl and <11.5g/dl, respectively). Although only a small number of the patients had anemia as defined by normal values, a retrospective analysis of individual patients over time revealed a sustained though small decrease in Hb from initial presentation. A statistically significant difference in Epo levels (P = 0.016 by Kruskal-Wallis test) was observed from the group with the lowest (Hb ≤11.5) to that with the highest (Hb ≥14.5) Hb values, with a median Epo value of 37 (interquartile range 24-42) vs. 13 (9-15) IU/l, respectively. In contrast, there was no evidence of an increased reticulocyte response to higher levels of Epo (r = 0.134 [Pearsons], P = 0.36). Reticulocyte counts ranged from 44 (38-57) to 76.5 (56-83) in the lowest and highest Hb groups, respectively. CONCLUSIONS -- Although only a small number of subjects in the group were overtly anemic, all subjects had an ongoing, small but significant decrease in Hb since presentation. This study of diabetic patients without nephropathy shows an expected increase in Epo production in response to lowering levels of Hb but without the expected reticulocyte response. [ABSTRACT FROM AUTHOR]

OBJECTIVE -- To study the effects of exercise on the absorption of the basal long-acting insulin analog insulin glargine (Lantus), administered subcutaneously in individuals with type 1 diabetes. RESEARCH DESIGN AND METHODS -- A total of 13 patients (12 men, 1 woman) with type 1 diabetes on a basal-bolus insulin regimen were studied. [sup 125]I-labeled insulin glargine at the usual basal insulin dose was injected subcutaneously into the thigh on the evening (2100) before the study day on two occasions 1 week apart. Patients were randomly assigned to 30 min intense exercise (65% peak oxygen uptake [Vo[sub 2peak]]) on one of these visits. The decay of radioactive insulin glargine was compared on the two occasions using a thallium-activated Nal gamma counter. Blood samples were collected at regular intervals on the study days to assess plasma glucose and insulin profiles. RESULTS -- No significant difference was found in the [sup 125]I-labeled insulin glargine decay rate on the two occasions (exercise vs. no exercise; repeated-measures ANOVA, P = 0.548). As expected, a significant fall in plasma glucose was observed over the exercise period (area under curve above fasting [ΔAUC] glucose: -0.39 ± 0.11 vs. -1.30 ± 0.16 mmol ⋅ 1[sup -1] ⋅ h[sup -1]; nonexercise vs. exercise; P = 0.001), but insulin levels did not differ significantly on the two occasions (ΔAUC insulin: -2.1 ± 3.9 vs. 1.5 ± 6.2 pmol ⋅ 1[sup -1] ⋅ h[sup -1]; nonexercise versus exercise; P = 0.507). CONCLUSIONS -- An intense 30-min period of exercise does not increase the absorption rate of the subcutaneously injected basal long-acting insulin analog insulin glargine in patients with type 1 diabetes. [ABSTRACT FROM AUTHOR]

Atherosclerotic disease accounts for much of the increased mortality and morbidity associated with type 2 diabetes. Epidemiological studies support the potential of improved glycemic control to reduce cardiovascular complications. An association between glycosylated hemoglobin (HbA1c) level and the risk for cardiovascular complications has frequently been reported. Most epidemiological data implicate postprandial hyperglycemia in the development of cardiovascular disease, whereas the link between fasting glycemia and diabetic complications is inconclusive. Moreover, in many studies, postprandial glycemia is a better predictor of cardiovascular risk than HbA1c level. Postprandial glucose may have a direct toxic effect on the vascular endothelium, mediated by oxidative stress that is independent of other cardiovascular risk factors such as hyperlipidemia. Postprandial hyperglycemia also may exert its effects through its substantial contribution to total glycemic exposure. The present review examines the hypothesis that controlling postprandial glucose level is an important strategy in the prevention of cardiovascular complications associated with diabetes. [ABSTRACT FROM AUTHOR]

Presents a study which determined the subcutaneous absorption rates and appearance in plasma of 3 formulations of the long-acting human insulin analog insulin glargine. Difference in zinc content of the formulations; Research design and methods; Discussion on the results.

Examines the concept of prandial glucose regulation in the management of type two diabetes in Great Britain. Clinical efficacy of glucose regulation; Factors in the development of diabetic complications; Value of combination therapy.

OBJECTIVE-To know whether age has an independent effect on the dawn phenomenon in noninsulin-using type 2 diabetes. RESEARCH DESIGN AND METHOD-Eighty-one individuals with type 2 diabetes were matched for HbA1c and divided by age into three subgroups of 27 individuals (1: ⩾70 years; 2: 60-69 years; and 3: ⩽59 years). All underwent ambulatory continuous glucose monitoring for quantifying the dawn phenomenon (i.e., the absolute [∂G, mg/dL] or relative [∂G%] increments from nocturnal nadirs to prebreakfast time points). RESULT-HbA1c levels and 24-h glycemic profiles were similar across the three groups. Glucose increments (mean ± SEM) were identical in the three groups: ∂G (mg/dL), 22.0 ± 4.7 (1), 21.3±3.6 (2), and 18.0±3.6 (3) and δG(%), 19.9±4.9 (1), 21.6±4.4 (2), and 17.6± 4.2 (3). Using the most common definition (∂G >10 mg/dL), the prevalence of the dawn phenomenon was 52, 70, and 59% in groups 1, 2, and 3, respectively. CONCLUSION-The dawn phenomenon is present in the elderly. [ABSTRACT FROM AUTHOR]

The authors comment on the study by Echouffo et al that investigated the association of visit-to-visit variability of fasting blood glucose with all-cause mortality but not with cardiovascular events in subjects without diabetes. They claim that the present study is unable to clarify whether the variability of overall glucose exposure is a risk factor or simple marker of adverse clinical outcome. Further, it failed to fully capture all potentialities provided by this long-term study.

A response by E. S. Kilpatrick, A. S. Rigby and S. L. Atkin to a letter to the editor about their article "The Effect of Glucose Variability on the Risk of Microvascular Complications in Type 1 Diabetes" in the 2006 issue is presented.

In January 2006, human insulin inhalation powder (Exubera; Pfizer) was approved by the US FDA and the EMEA for the treatment of adult patients with diabetes mellitus. It is the first non-injectable insulin to be approved. [ABSTRACT FROM AUTHOR]

The prevalence of diabetes mellitus is steadily increasing in Western society, with obvious implications for costs to health-care providers. A project plan to transform local care has been established in Wales to enable diabetic patients to self-manage their disease by improving education and access to information and tests locally. The plan involves the establishment of local diabetes centres providing educational resources to the patients, carers and health professionals. It envisages that the local diabetes community centres will provide all aspects of diabetic care, from diagnosis to continuing management, with the aid of modern communications technology. [ABSTRACT FROM AUTHOR]

Abstract: As non-communicable or chronic diseases are a growing threat to human health and economic growth, political stakeholders are aiming to identify options for improved response to the challenges of prevention and management of non-communicable diseases. This paper is intended to contribute ideas on personalized chronic disease management which are based on experience with one major chronic disease, namely diabetes mellitus. Diabetes provides a pertinent case of chronic disease management with a particular focus on patient self-management. Despite advances in diabetes therapy, many people with diabetes still fail to achieve treatment targets thus remaining at risk of complications. Personalizing the management of diabetes according to the patient''s individual profile can help in improving therapy adherence and treatment outcomes. This paper suggests using a six-step cycle for personalized diabetes (self-)management and collaborative use of structured blood glucose data. E-health solutions can be used to improve process efficiencies and allow remote access. Decision support tools and algorithms can help doctors in making therapeutic decisions based on individual patient profiles. Available evidence about the effectiveness of the cycle''s constituting elements justifies expectations that the diabetes management cycle as a whole can generate medical and economic benefit. [Copyright &y& Elsevier]

Abstract: Background:: Type 2 diabetes is characterized by agradual decline in insulin secretion in response to nutrient loads; hence, it is primarily a disorder of post-prandial glucose (PPG) regulation. However, physicians continue to rely on fasting plasma glucose (FPG) and glycosylated hemoglobin (HbA1c) to guide management Objectives:: The objectives of this article are to review current data on postprandial hyperglycemia and to assess whether, and how, management of type 2 diabetes should change to reflect new clinical findings. Methods:: Articles were selected from MEDLINE searches (key words: postprandial glucose, postprandial hyperglycemia, and cardiovascular disease) and from our personal reference files, with emphasis on the contribution of postprandial hyperglycemia to overall glycemic load or cardiovascular (CV) risk. Results:: About 33% of people diagnosed as having type 2 diabetes based on postprandial hyperglycemia have normal FPG. PPG contributes ≥70% to the total glycemic load in patients who are fairly well controlled (HbA,1c ≤.3%). Furthermore, there is a linear relationship between the risk of CV death and the 2-hour oral glucose tolerance test (OGTT). Increased mortality is evident at OGTT levels of ∼90 mg/dL (5 mmol/L), which is well below current definitions of type 2 diabetes. Biphasic insulin aspart was shown to be more effective at reducing HbAlc below currently recommended levels than basal insulin glargine (66% vs 40%; P < 0.001), and it reduced endothelial dysfunction more effectively than regular insulin (P < 0.01). Repaglinide achieved regression of carotid atherosclerosis (intima-media thickness) in 52% of patients versus 18 % for glyburide (P < 0.01) over 1 year, although levels of HbAlc and CV risk factors were similar for both treatment groups. Finally, acarbose reduced the relative risk of CV events by 49% over 3.3 years versus placebo in patients with impaired glucose tolerance (2.2% vs 4.7%; P = 0.03) and by 35% over ≥1 year in patients with type 2 diabetes (9.4% vs 6.1%; P = 0.006). Conclusions:: All components of the glucose triad (ie,FPG, HbA1c, and PPG) should be considered in the management of type 2 diabetes. Therapy targeted at PPG has been shown to improve glucose control and to reduce the progression of atherosclerosis and CV events; therefore, physicians should consider monitoring and targeting PPG, as well as HbAlc and FPG, in patients with type 2 diabetes. [Copyright &y& Elsevier]